@article {pmid40267966, year = {2025}, author = {Brinkman, N and Teunis, T and Choi, S and Ring, D and Brode, WM}, title = {Factors associated with the presence and intensity of ongoing symptoms in Long COVID.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319874}, doi = {10.1371/journal.pone.0319874}, pmid = {40267966}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/complications/epidemiology/psychology/pathology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Aged ; SARS-CoV-2/isolation & purification ; Anxiety ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Risk Factors ; }, abstract = {OBJECTIVE: Identification of modifiable factors associated with symptom intensity among people seeking care for Post-Acute Sequelae of SARS-CoV-2 infection (PASC) could help guide the development of comprehensive, whole-person care pathways to alleviate symptoms irrespective of potential underlying pathophysiologies. We aimed to better define the key contributors to PASC, and sought the factors associated with PASC symptom presence and intensity.

METHODS: In this cross-sectional study, 249 patients presenting for PASC care at a dedicated Post-COVID-19 clinic completed a standardized screening assessment prior to initial visit and evaluation by a general internist or nurse practitioner. We measured 46 symptoms based on the WHO's Global COVID-19 Clinical Platform Case Report Form for Post COVID Condition and performed a factor analysis and item response theory based 2-parameter logistic model to develop a population-based t-score to measure PASC symptom presence and intensity (PASC-SPI). A multivariable linear regression analysis was used to assess factors associated with PASC-SPI, accounting for demographics, comorbidities, COVID-19 infection duration and severity, and mental health.

RESULTS: Greater PASC-SPI was associated with greater symptoms of anxiety, a longer duration of COVID-19 infection, and hypercholesterolemia. Lower PASC-SPI was associated with older age, self-reported 1-3 units of alcohol per week, and self-reported clinician confirmation of COVID-19 diagnosis. Symptoms of anxiety accounted for a considerably higher proportion of variation in PASC-SPI than other variables.

CONCLUSION: Symptoms of anxiety were the strongest correlate of PASC-SPI, highlighting it as both a potential neuroinflammatory marker of PASC and a modifiable component of the illness. This emphasizes the need for comprehensive, whole person treatment strategies that integrate evidence-based interventions to address the multifaceted nature of PASC.}, } @article {pmid40265979, year = {2025}, author = {Belton, S and Sheridan, K}, title = {'The Second Arrow': A Collaborative Autoethnographic Exploration of What Can Be Learned From One Long COVID Journey.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {3}, pages = {e70227}, doi = {10.1111/hex.70227}, pmid = {40265979}, issn = {1369-7625}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/psychology/rehabilitation ; Female ; Anthropology, Cultural ; SARS-CoV-2 ; Chronic Disease/psychology ; }, abstract = {INTRODUCTION: Long COVID is a complex multisystem illness with multiple relapsing-remitting symptoms, which can vary in severity and impact people's daily lives. This study utilises the first author's experience of falling ill with and recovering from long COVID to investigate the lived experience of the illness. Learnings that could positively influence how people with long COVID, and health professionals, approach rehabilitation and recovery from the illness going forward are identified.

METHODS: Employing collaborative autoethnography, the first author investigated her personal experience of falling ill with, and rehabilitating from, long COVID, while soliciting input of the second author (an athletic therapist and physiotherapist, and researcher with expertise in chronic pain) for the purpose of analysis and interpretation. Reflexive thematic analysis was employed across a number of data sources available to the first author, including journal entries, text messages, emails, and pharmacy receipts.

RESULTS: Four themes were generated from the data, supported by a number of subthemes: (i) Psychosocial impact of long COVID, (ii) Invalidated, (iii) Validated, and (iv) Power and Ownership. The negative impact of a siloed and reductionist approach to care for long COVID is evident in the findings of this study. In addition, the need for healthcare environments that enhance autonomy and empowerment, and that implement patient-centred care, where the person living with chronic illness is supported to engage in management strategies that meet their needs, is underlined.

CONCLUSION: This study highlights the detrimental cost, both personally and financially, of the ongoing use of the biomedical model of care in the treatment of long COVID. Findings support the need for an interdisciplinary approach to care that considers the whole person and adopts a biopsychosocial approach to care. Furthermore, the need for healthcare professionals to actively listen to, respect, validate and support the person living with long COVID on their individualised recovery journey is evident.

The first author was a long COVID patient, the context and extent of this is explained within the paper. As such, this paper is developed and written primarily from the perspective of a patient, as a first-hand narrative of the recovery journey from the illness, with the insights of a clinician (second author) providing context and the potential for a broader understanding of the journey. The goal of this work is, through the dissemination of the paper's findings, to improve pathways and outcomes for others living with long COVID.}, } @article {pmid40265173, year = {2025}, author = {Cheng, AL and DeFranco, AR and Furman, M and Hackert, SM and Hunt, DM and Marschall, J and McQueen, A}, title = {Shared Medical Appointments to Improve Equitable Access to Rehabilitative Care for Long COVID.}, journal = {Cardiopulmonary physical therapy journal}, volume = {36}, number = {1}, pages = {50-57}, pmid = {40265173}, issn = {1541-7891}, support = {U18 HS029911/HS/AHRQ HHS/United States ; }, abstract = {Long COVID is an infection-associated chronic condition that can cause a wide variety of symptoms and long-term functional impairments. While investigation into curative treatment is ongoing, current standard management of Long COVID relies heavily on rehabilitative care by physical, occupational, and speech therapists. Unfortunately, many persons with Long COVID encounter financial barriers to receiving rehabilitative care, especially because some state Medicaid programs and safety net health insurance plans do not cover one-on-one rehabilitation visits. Shared Medical Appointments (SMAs) are group visits which can deliver multidisciplinary care, and they are widely reimbursed by health insurance plans. SMAs also offer the added benefit of peer support and camaraderie, and they are an efficient method for clinicians to deliver care to many patients at once. SMAs can serve as an innovative method of delivering rehabilitative care for persons with Long COVID who cannot access individual appointments with a physical, occupational, and/or speech therapist. The purpose of this clinical perspective is to present the rationale, development, and organization and content of a six-session curriculum of SMAs that was created to deliver rehabilitation principles for Long COVID management. The curriculum covers physical activity, daily living activities, and thinking and speaking. It includes identification of functional concerns and goals, instruction in rehabilitative strategies and tools, and troubleshooting challenges that are encountered as patients implement strategies. The content in this clinical perspective is intended to be easily adapted and delivered by other clinicians in order to facilitate more equitable access to Long COVID rehabilitative care.}, } @article {pmid40263530, year = {2025}, author = {Zhang, L and Wen, J and Yuan, L and Yan, Y and Zhang, Z and Li, K and Tang, Z}, title = {Anxiety and depression in healthcare workers 2 years after COVID-19 infection and scale validation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13893}, pmid = {40263530}, issn = {2045-2322}, support = {SY202215//Suqian Sci&Tech Program/ ; SY202215//Suqian Sci&Tech Program/ ; SY202215//Suqian Sci&Tech Program/ ; SY202215//Suqian Sci&Tech Program/ ; SY202215//Suqian Sci&Tech Program/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Health Personnel/psychology ; Female ; Male ; Adult ; *Anxiety/epidemiology/etiology/diagnosis/psychology ; *Depression/epidemiology/diagnosis/etiology/psychology ; Cross-Sectional Studies ; Middle Aged ; SARS-CoV-2 ; Reproducibility of Results ; Surveys and Questionnaires ; Young Adult ; }, abstract = {This study aims to assess the levels of anxiety and depression among healthcare workers two years post COVID-19 infection and to validate the reliability and validity of the PHQ-9 and GAD-7 scales in this population. This cross-sectional study was conducted in June 2024 using a simple random sampling approach to survey healthcare institution workers. A total of 1038 valid samples were collected, and anxiety and depression levels were assessed using the PHQ-9 and GAD-7 scales. Participants included healthcare workers such as doctors, nurses, administrative staff, and students. Data analysis included descriptive statistics, correlation analysis, univariate, and multivariate analyses to explore the effects of variables such as occupation and gender on anxiety and depression. Long COVID was reported in 50.8% of participants. Occupational categories significantly influenced anxiety and depression levels: compared to students (reference group), doctors, nurses, and administrative staff exhibited significantly lower scores. Non-long COVID participants showed significantly lower anxiety and depression scores than those with long COVID. Additionally, the PHQ-9 and GAD-7 scales demonstrated high reliability and validity among COVID-19 population. Two years after COVID-19 infection, anxiety and depression levels among healthcare institution workers remain significantly influenced by occupational category and long COVID status. For healthcare workers, particularly those with long COVID and student groups, policymakers and healthcare administrators should consider optimizing mental health support systems. This includes implementing regular mental health screenings, providing personalized psychological interventions, offering counseling services, reducing work-related stress, and promoting the use of mental health assessment tools to improve the psychological well-being of this population.}, } @article {pmid40261198, year = {2025}, author = {Cheng, AL and Herman, E and Abramoff, B and Anderson, JR and Azola, A and Baratta, JM and Bartels, MN and Bhavaraju-Sanka, R and Blitshteyn, S and Fine, JS and Fleming, TK and Verduzco-Gutierrez, M and Herrera, JE and Karnik, R and Kurylo, M and Longo, MT and McCauley, MD and Melamed, E and Miglis, MG and Neal, JD and Oleson, CV and Putrino, D and Rydberg, L and Silver, JK and Terzic, CM and Whiteson, JH and Niehaus, WN}, title = {Multidisciplinary collaborative guidance on the assessment and treatment of patients with Long COVID: A compendium statement.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1002/pmrj.13397}, pmid = {40261198}, issn = {1934-1563}, abstract = {BACKGROUND: In 2021, the American Academy of Physical Medicine and Rehabilitation established the Multi-Disciplinary Post-Acute Sequelae of SARS-CoV-2 Infection Collaborative to provide guidance from established Long COVID clinics for the evaluation and management of Long COVID. The collaborative previously published eight Long COVID consensus guidance statements using a primarily symptom-based approach. However, Long COVID symptoms most often do not occur in isolation.

AIMS: This compendium aims to equip clinicians with an efficient, up-to-date clinical resource for evaluating and managing adults experiencing Long COVID symptoms. The primary intended audience includes physiatrists, primary care physicians, and other clinicians who provide first-line assessment and management of Long COVID symptoms, especially in settings where subspecialty care is not readily available. This compendium provides a holistic framework for assessment and management, symptom-specific considerations, and updates on prevalence, health equity, disability considerations, pathophysiology, and emerging evidence regarding treatments under investigation. Because Long COVID closely resembles other infection-associated chronic conditions (IACCs) such as myalgic encephalomyelitis/chronic fatigue syndrome, the guidance in this compendium may also be helpful for clinicians managing these related conditions.

METHODS: Guidance in this compendium was developed by the collaborative's established modified Delphi approach. The collaborative is a multidisciplinary group whose members include physiatrists, primary care physicians, pulmonologists, cardiologists, psychiatrists, neuropsychologists, neurologists, occupational therapists, physical therapists, speech and language pathologists, patients, and government representatives. Over 40 Long COVID centers are represented in the collaborative.

RESULTS: Long COVID is defined by the National Academies of Sciences, Engineering, and Medicine as "an IACC that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems." The current global prevalence of Long COVID is estimated to be 6%. Higher prevalence has been identified among female gender, certain racial and ethnic groups, and individuals who live in nonurban areas. However, anyone can develop Long COVID after being infected with the SARS-CoV-2 virus. Long COVID can present as a wide variety of symptom clusters. The most common symptoms include exaggerated fatigue and diminished energy windows, postexertional malaise (PEM)/postexertional symptom exacerbation (PESE), cognitive impairment (brain fog), dysautonomia, pain/myalgias, and smell and taste alterations. Holistic assessment should include a traditional history, physical examination, and additional diagnostic testing, as indicated. A positive COVID-19 test during acute SARS-CoV-2 infection is not required to diagnose Long COVID, and currently, there is no single laboratory finding that is definitively diagnostic for confirming or ruling out the diagnosis of Long COVID. A basic laboratory assessment is recommended for all patients with possible Long COVID, and consideration for additional labs and diagnostic procedures is guided by the patient's specific symptoms. Current management strategies focus on symptom-based supportive care. Critical considerations include energy conservation strategies and addressing comorbidities and modifiable risk factors. Additionally, (1) it is essential to validate the patient's experience and provide reassurance that their symptoms are being taken seriously because many patients have had their symptoms dismissed by loved ones and clinicians; (2) physical activity recommendations must be carefully tailored to the patient's current activity tolerance because overly intense activity can trigger PEM/PESE and worsened muscle damage; and (3) treatment recommendations should be delivered with humility because there are many persistent unknowns related to Long COVID. To date, there are limited data to guide medication management specifically in the context of Long COVID. As such, medication use generally follows standard practice regarding indications and dosing, with extra attention to prioritize (1) patient preference via shared decision-making and (2) cautious use of medications that may improve some symptoms (eg, cognitive/attention impairment) but may worsen other symptoms (eg, PEM/PESE). Numerous clinical trials are investigating additional treatments. The return-to-work process for individuals with Long COVID can be challenging because symptoms can fluctuate, vary in nature, affect multiple functional areas (eg, physical and cognitive), and often manifest as an "invisible disability" that may not be readily acknowledged by employers or coworkers. Clinicians can help patients return to work by identifying suitable workplace accommodations and resources, providing necessary documentation, and recommending occupational or vocational therapy when needed. If these efforts are unsuccessful and work significantly worsens Long COVID symptoms or impedes recovery, applying for disability may be warranted. Long COVID is recognized as a potential disability under the Americans with Disabilities Act.

CONCLUSION: To contribute to the overall health and well-being for all patients, Long COVID care should be delivered in a holistic manner that acknowledges challenges faced by the patient and uncertainties in the field. For more detailed information on assessment and management of specific Long COVID symptoms, readers can reference the collaborative's symptom-specific consensus guidance statements.}, } @article {pmid40260126, year = {2025}, author = {Al-Oraibi, A and Woolf, K and Naidu, J and Nellums, LB and Pan, D and Sze, S and Tarrant, C and Martin, CA and Gogoi, M and Nazareth, J and Divall, P and Dempsey, B and Lamb, D and Pareek, M}, title = {Global prevalence of long COVID and its most common symptoms among healthcare workers: a systematic review and meta-analysis.}, journal = {BMJ public health}, volume = {3}, number = {1}, pages = {e000269}, pmid = {40260126}, issn = {2753-4294}, abstract = {OBJECTIVES: Long COVID, a condition where symptoms persist after the acute phase of COVID-19, is a significant concern for healthcare workers (HCWs) due to their higher risk of infection. However, there is limited knowledge regarding the prevalence, symptoms and clustering of long COVID in HCWs. We aimed to estimate the pooled prevalence and identify the most common symptoms of long COVID among HCWs who were infected with SARS-CoV-2 virus globally, and investigate any differences by geographical region and other factors.

DESIGN: Systematic review and meta-analysis (PROSPERO CRD42022312781).

DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, PsycINFO and the grey literature from 31 December 2019 until 18 February 2022.

ELIGIBILITY CRITERIA: We included studies reporting primary data on long COVID prevalence and symptoms in adult HCWs who had SARS-CoV-2 infection.

DATA EXTRACTION AND SYNTHESIS: Methodological quality was assessed using the Joanna Briggs Institute checklist. Meta-analysis was performed for prevalence data of long COVID following SARS-CoV-2 infection.

RESULTS: Out of 5737 articles, 28 met the inclusion criteria, with a combined sample size of 6 481 HCWs. 15 articles scored equal to or above the median score for methodological quality. The pooled prevalence of long COVID among HCWs who had SARS-CoV-2 infection was 40% (95% CI: 29% to 51%, I[2]: 97.2%; 12 studies), with a mean follow-up period of 22 weeks. The most prevalent symptoms reported were fatigue (35%), neurologic symptoms (25%), loss/decrease of smell and/or taste (25%), myalgia (22%) and shortness of breath (19%).

CONCLUSION: This review highlights the substantial burden of long COVID among HCWs worldwide. However, limitations in data quality and inconsistent definitions of long COVID impact the generalisability of these findings. To improve future interventions, we recommend enhanced cohort study designs for better characterisation of long COVID prevalence and symptoms in HCWs.}, } @article {pmid40259893, year = {2025}, author = {von Falkenhausen, AS and Gail, A and Geipel, S and Scherer, C and Stockhausen, S and Sams, LE and Becker, F and Massberg, S and Kääb, S and Sinner, MF}, title = {Symptoms of Depression and Anxiety After COVID-19 Despite Systematic Telemedical Care: Results From the Prospective COVID-SMART Study.}, journal = {Depression and anxiety}, volume = {2025}, number = {}, pages = {9989990}, pmid = {40259893}, issn = {1520-6394}, mesh = {Humans ; *COVID-19/psychology/complications/therapy/epidemiology ; Male ; Female ; *Telemedicine ; Middle Aged ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; Adult ; Prospective Studies ; Aged ; Prevalence ; }, abstract = {Background: Long-COVID has attracted increased attention with rising numbers of affected patients and high individual symptom burden. Prior studies have described its prevalence, course of disease, and severity. Yet, the influence of intensive care, including telemedical support for patients at risk for a severe course of the initial COVID-19 disease, on the occurrence of Long-COVID and its associated symptoms is studied to a lesser extent. Methods: Here, we report the long-term results of the COVID-SMART study, which randomized at-risk COVID-19 patients to either smartwatch-based monitoring with telemedical support or standard care. We investigate Long-COVID symptoms, including symptoms of depression and anxiety after 12 months. Findings: Between October 2020 and May 2022, we enrolled 607 patients in the COVID-SMART study. Complete 12-month follow-up was available for 573 patients, with 288 patients randomized to the intervention group and 285 to the control group. Overall, 234 participants (40.8%) reported COVID-related symptoms, with a high prevalence of symptoms of depression (209 participants, 36.5%) and anxiety (232 participants, 40.5%). However, telemedical support did not reduce these symptoms at follow-up. Multivariable regression analysis identified sex, active smoking, and pre-existing asthma as significant predictors of both outcomes. Interpretation: COVID-SMART is the first prospective, randomized clinical trial to systematically assess the impact of telemedical care on the development of Long-COVID associated risk of depression and anxiety. We identify in part modifiable risk factors for these outcomes. However, telemedical support does not appear to be beneficial in reducing symptoms of anxiety and depression and should hence be focused to the acute infection phase. Trial Registration: ClinicalTrials.gov identifier: NCT04471636.}, } @article {pmid40196285, year = {2025}, author = {Zhang, B and Wu, Q and Jhaveri, R and Zhou, T and Becich, MJ and Bisyuk, Y and Blanceró, F and Chrischilles, EA and Chuang, CH and Cowell, LG and Fort, D and Horowitz, CR and Kim, S and Ladino, N and Liebovitz, DM and Liu, M and Mosa, ASM and Schwenk, HT and Suresh, S and Taylor, BW and Williams, DA and Morris, JS and Forrest, CB and Chen, Y}, title = {Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {40196285}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {IMPORTANCE: Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.

OBJECTIVE: To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population.

This retrospective cohort study used data from the RECOVER consortium comprising 40 children's hospitals and health institutions in U.S. between January 2022 and October 2023.

EXPOSURES: A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection.

MAIN OUTCOMES AND MEASURES: PASC was identified using two approaches: (1) the ICD-10-CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching.

RESULTS: A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to ; arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to ; fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were consistent across various organ systems, including cardiovascular, respiratory, gastrointestinal, neurological, and musculoskeletal systems.

CONCLUSIONS AND RELEVANCE: Children and adolescents face significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings suggest a cumulative risk of PASC and highlight the urgent need for targeted prevention strategies to reduce reinfections, which includes an increased emphasis on initial or re-vaccination of children.}, } @article {pmid40259865, year = {2025}, author = {Bjorvatn, B and Merikanto, I and Chung, F and Holzinger, B and Morin, CM and Penzel, T and De Gennaro, L and Dauvilliers, Y and Wing, YK and Benedict, C and Xue, P and Reis, C and Korman, M and Landtblom, AM and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Berezin, L and Sarkanen, T and Liu, Y and Scarpelli, S and Brandao, LEM and Cedernaes, J and Fränkl, EC and Partinen, E and Bolstad, CJ and Plazzi, G and Partinen, M and Espie, CA}, title = {Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).}, journal = {Journal of sleep research}, volume = {}, number = {}, pages = {e70076}, doi = {10.1111/jsr.70076}, pmid = {40259865}, issn = {1365-2869}, abstract = {To study the impact of the COVID-19 pandemic on sleep and circadian rhythms-two fundamental pillars for health-the collaboration International COVID-19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questionnaire to cover changes in sleep and sleep disorders, as well as physical and mental health. Two survey waves were conducted, one in 2020 and another one in 2021. In ICOSS-1, a total of 26,539 people from 14 countries across four continents (Europe, Asia, North and South America) participated. In ICOSS-2, two more countries joined ICOSS, and 15,813 people participated. The focus in ICOSS-2 was on Long COVID. Participants accessed the widely disseminated online surveys in their native language. In the 20 papers published so far, the surveys have uncovered several novel findings, including how the pandemic impacted sleep patterns, the prevalence of sleep disorders, chronotype-based differences and sleep-immune system interactions. To the best of our knowledge, there is no other large-scale multinational study targeting the general population investigating the role of sleep and sleep disorders alongside a variety of psychological, biological, social and economic factors during the recent COVID-19 pandemic.}, } @article {pmid40259563, year = {2025}, author = {Cornish, F and Sabaine, B and Soares, L and Caldas, B and Portela, MC and Bousquat, A and Aveling, EL}, title = {The erasure of infection-associated chronic conditions: Critical interpretive synthesis of literature on healthcare for long COVID and related conditions in Brazil.}, journal = {Global public health}, volume = {20}, number = {1}, pages = {2490720}, doi = {10.1080/17441692.2025.2490720}, pmid = {40259563}, issn = {1744-1706}, mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/therapy/complications ; Chronic Disease/epidemiology/therapy ; SARS-CoV-2 ; *Delivery of Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {Evidence is emerging that long COVID is at least as prevalent in the Global South as the Global North, but literature on long COVID healthcare in the Global South is in its infancy. Brazil is seeing significant levels of debility due to long COVID but a limited national evidence-base. long COVID shares symptomatology and appropriate care with a wider category of infection-associated chronic conditions (IACCs). This article reviews literature published between 2000 and 2023 addressing healthcare for long COVID and IACCs in Brazil, in the interest of exploring challenges and opportunities for the SUS (Brazil's universal health system) to offer appropriate long COVID healthcare. We find that long COVID and IACCs collectively are subject to erasure from Brazilian healthcare knowledge, through lack of expertise, a resource-limited health system prioritising urgent care, and the concentration of poor health in marginalised populations with limited decision-making power. A nascent intellectual will to address long COVID, and a tradition of social participation in healthcare governance present potential opportunities. We call for ignition of a global step-change in tackling healthcare for long COVID and IACCs. Global equity in long COVID healthcare requires the development and sharing of expertise regarding its universal and context-specific features.}, } @article {pmid40258532, year = {2025}, author = {Berends, MS and Homburg, M and Kupers, T and Meijer, EN and Bos, I and Verheij, R and Kuiper, J and Berger, MY and Peters, LL}, title = {Impact of Pre-Existing Comorbidities and Multimorbidities, Demography and Viral Variants on Post-Acute Sequelae of COVID-19 ('Long COVID') in Dutch Primary Care: A Retrospective Cohort Study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {}, number = {}, pages = {107912}, doi = {10.1016/j.ijid.2025.107912}, pmid = {40258532}, issn = {1878-3511}, abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC), or Long COVID, involves persistent symptoms following acute infection, posing a global health challenge. While a growing number of studies have investigated potential predictors and risk factors, uncertainties remain regarding their consistency and clinical applicability. This study investigates PASC prevalence, comorbidities, demographics, and viral variants using Dutch primary care electronic healthcare records (EHR).

METHODS: A retrospective cohort study used EHR data from 59 general practices in northern Netherlands, including 19,638 SARS-CoV-2 PCR-positive patients from January 1, 2020, to December 31, 2021. PASC was identified via WHO and CDC guidelines, a Dutch Word2Vec model, and clinical assessments. Relative risk (RR) calculations analyzed comorbidities, demographics, and viral variants.

RESULTS: PASC prevalence was 5.8% (CI95%: 5.4-6.1%). Comorbidities significantly increasing PASC risk included lung disease (RR: 1.95), cardiovascular disease (RR: 1.73), diabetes (RR: 1.82), kidney disease (RR: 1.98), and mental illness (RR: 1.29). Females and individuals aged ≥45 had increased risk. Multivariate regression revealed higher odds of prolonged PASC for ages 45-59 (AOR: 3.02), 60-74 (AOR: 3.25), and 75+ (AOR: 2.44). Combined mental illness and lung disease further increased risk (AOR: 2.55).

CONCLUSION: Chronic conditions, multimorbidity, and demographics significantly influence PASC onset and duration. Targeted interventions may mitigate its long-term impact.}, } @article {pmid40257144, year = {2025}, author = {Caamaño, E and Rodrigo, LV and Garcia-Ramos, S and Garcia, AC and Cerro, SR and Power, M and Asencio, JM and Piñeiro, P and Hortal, J and Garutti, I}, title = {Risk factors for readmission of COVID-19 ICU survivors: A three-year follow up.}, journal = {The Indian journal of medical research}, volume = {161}, number = {2}, pages = {190-198}, doi = {10.25259/IJMR_726_2024}, pmid = {40257144}, issn = {0971-5916}, mesh = {Humans ; *COVID-19/mortality/therapy/epidemiology ; Male ; *Patient Readmission/statistics & numerical data ; Female ; *Intensive Care Units/statistics & numerical data ; Risk Factors ; Middle Aged ; *Survivors/statistics & numerical data ; Follow-Up Studies ; Aged ; Prospective Studies ; SARS-CoV-2 ; Length of Stay/statistics & numerical data ; Adult ; }, abstract = {Background & objectives Evidence suggests that individuals who have been hospitalised due to COVID-19 are more susceptible to future mortality and readmission, thereby imposing a substantial strain on their quality of life. The available data on intensive care unit (ICU) survivors, particularly in terms of long-term outcomes, is notably insufficient. This study focused on the long-term outcomes for ICU survivors of COVID-19, specifically readmission and mortality, as well as possible risk factors that could lead to their need for readmission. Methods We conducted a prospective observational study of 505 individuals admitted to the ICU of a tertiary care hospital between March 2020 and March 2021. Follow up concluded in January 2024. We evaluated the need for hospital and ICU readmissions, examining potential risk factors, including patient comorbidities, clinical situation at the time of the previous hospital and ICU admission, and evolution and treatment in the ICU. As a secondary objective, we determined the prevalence of long-term mortality. Results Among 341 ICU survivors, 75 (22%) required hospital readmission, with a median time to readmission of 415 days (IQR: 166-797). The most frequent cause of readmission was respiratory conditions (29.3%). The median hospital stay during readmission was six days. Independent risk factors for hospital readmission included age, elevated creatinine levels at ICU admission, and length of stay in the ICU. Of the 75 readmitted to the hospital, 19 required ICU readmission. Ten individuals died following hospital discharge. Interpretation & conclusions Patients requiring ICU admission due to COVID-19 have a significant risk of hospital readmission, particularly those with advanced age, elevated creatinine levels at ICU admission, and longer ICU stays.}, } @article {pmid40256946, year = {2025}, author = {}, title = {Comment on "Intermittent Hypoxic-Hyperoxic Training During Inpatient Rehabilitation Improves Exercise Capacity and Functional Outcome in Patients With Long Covid: Results of a Controlled Clinical Pilot Trial" by Doehner et al.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {2}, pages = {e13802}, doi = {10.1002/jcsm.13802}, pmid = {40256946}, issn = {2190-6009}, } @article {pmid40256447, year = {2025}, author = {Cheetham, NJ and Bowyer, V and García, MP and Bowyer, RCE and Carpentieri, JD and Guise, A and Thompson, EJ and Sudre, CH and Molteni, E and Antonelli, M and Penfold, RS and Harvey, NR and Canas, LS and Rjoob, K and Murray, B and Kerfoot, E and Hammers, A and Ourselin, S and Duncan, EL and Steves, CJ and , }, title = {Social determinants of recovery from ongoing symptoms following COVID-19 in two UK longitudinal studies: a prospective cohort study.}, journal = {BMJ public health}, volume = {3}, number = {1}, pages = {e001166}, pmid = {40256447}, issn = {2753-4294}, abstract = {INTRODUCTION: Social gradients in COVID-19 exposure and severity have been observed internationally. Whether combinations of pre-existing social factors, particularly those that confer cumulative advantage and disadvantage, affect recovery from ongoing symptoms following COVID-19 and long COVID is less well understood.

METHODS: We analysed data on self-perceived recovery following self-reported COVID-19 illness in two UK community-based cohorts, COVID Symptom Study Biobank (CSSB) (N=2548) and TwinsUK (N=1334). Causal effects of sociodemographic variables reflecting status prior to the COVID-19 pandemic on recovery were estimated with multivariable Poisson regression models, weighted for inverse probability of questionnaire participation and COVID-19 infection and adjusted for potential confounders. Associations between recovery and social strata comprising combinations of sex, education level and local area deprivation were estimated using the intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) approach. Further analyses estimated associations with variables reflecting experiences during the pandemic.

RESULTS: Gradients in recovery from COVID-19 along the lines of social advantage were observed in intersectional MAIHDA models, with predicted probability of recovery lowest in female strata with lowest education and highest deprivation levels (CSSB: 55.1% (95% CI 44.0% to 65.1%); TwinsUK: 73.9% (95% CI 61.1% to 83.0%)) and highest in male strata with highest education and lowest deprivation levels (CSSB: 79.1% (95% CI 71.8% to 85.1%); TwinsUK: 89.7% (95% CI 82.5% to 94.1%)). Associations were not explained by differences in prepandemic health. Adverse employment, financial, healthcare access and personal experiences during the pandemic were also negatively associated with recovery.

CONCLUSIONS: Inequalities in likelihood of recovery from COVID-19 were observed, with ongoing symptoms several months after coronavirus infection more likely for individuals with greater social disadvantage prior to the pandemic.}, } @article {pmid40256200, year = {2025}, author = {Naik, H and Pongratz, K and Malbeuf, M and Kung, S and Last, L and Sugiyama, A and Khor, E and McGuire, M and Levin, A and Tran, KC}, title = {MyGuide long COVID: An online self-management tool for people with long COVID.}, journal = {Internet interventions}, volume = {40}, number = {}, pages = {100825}, pmid = {40256200}, issn = {2214-7829}, abstract = {BACKGROUND: Long COVID is a relatively new condition for which patients are asked to employ self-management strategies to manage their symptoms. However, it can be challenging for individuals with long COVID to find reliable and actionable self-management resources. The objective of this project was to develop an online tool for individuals with long COVID that is patient-centered, accessible, and customizable to meet individual needs.

METHODS: MyGuide Long COVID (www.longCOVIDguide.ca) was developed in British Columbia (BC), Canada, by a team that included long COVID clinicians and patient partners. Site visitors answer questions about their symptoms, and MyGuide generates a curated set of self-management resources tailored to their needs. Since its launch in August 2023, Google Analytics has been used to monitor website activity.

RESULTS: Within the first year, MyGuide had 52,578 total page views and 8570 new users. The most popular method to access MyGuide was by computer (56.3 % of users), and the most represented city was Vancouver, BC (23.5 % of users). The most popular topics were "Post Exertional Malaise" (1339 sessions) and "What is long COVID?" (1257 sessions).

CONCLUSIONS: An online tool to support chronic disease self-management can be successfully co-developed with patient partners and engagement tracked using web analytics.}, } @article {pmid40256045, year = {2025}, author = {Birnie, E and Vergouwe, M and Appelman, B and Biemond, JJ and Heijmans, J and Nichols, BE and Wiersinga, WJ and Popping, S and , }, title = {Cost-effectiveness Analysis of Nirmatrelvir/Ritonavir for COVID-19 Among Individuals at High Risk: A Modeling Study.}, journal = {Open forum infectious diseases}, volume = {12}, number = {4}, pages = {ofaf187}, pmid = {40256045}, issn = {2328-8957}, abstract = {BACKGROUND: To prevent severe disease, nirmatrelvir/ritonavir (nirmatrelvir/r) is administered to individuals infected with SARS-CoV-2 who are at high risk, and it is currently priced at approximately $1375 in the Netherlands. We aim to evaluate the health outcomes and cost-effectiveness of nirmatrelvir/r among patients with high risk of severe disease.

METHODS: We used a decision-analytic model parameterized with clinical and health care utilization data from individuals at high risk who were infected with SARS-CoV-2 between September 2021 and November 2023. We assumed baseline event rates of 1% for hospitalization and 0.05% for intensive care unit admission. Nirmatrelvir/r-related factors were varied. Costs were collected from a third-party payer's perspective, and the cost-effectiveness threshold was <$88 000 per quality-adjusted life-year gained. Sensitivity analyses were performed to account for uncertainties.

RESULTS: This study included 949 individuals at high risk who were infected with SARS-CoV-2. The sample had a median age of 65 years (IQR, 53-75), and 416 (44%) participants were female. Comorbidities included obesity (25%), hematologic malignancy (21%), solid organ/stem cell transplantation (17%), and immunosuppressive medication use (47%). With an assumed low effectiveness, nirmatrelvir/r could reduce hospitalizations and deaths (relative risk reduction, 21% and 44%, respectively). With high effectiveness, relative risk reductions of 89% and 90% were calculated for hospitalizations and deaths. Higher baseline rates for intensive care unit and hospital admission positively influenced cost-effectiveness thresholds. Nirmatrelvir/r is cost-effectively priced at <$512 with low effectiveness and <$1071 with high effectiveness.

CONCLUSIONS: With current low baseline event rates for hospitalization, nirmatrelvir/r has the potential, not only to reduce hospitalizations and deaths in individuals with COVID-19 who are at high risk, but to do so cost-effectively with a drug price reduction of 22% to 63%. These findings are relevant for policy makers and physicians and emphasize the importance of reevaluating current drug pricing.

CLINICAL TRIALS REGISTRATION: NCT05195060 (ClinicalTrials.gov).}, } @article {pmid40254623, year = {2025}, author = {Mksoud, M and Ittermann, T and Holtfreter, B and Söhnel, A and Söhnel, C and Welk, A and Paris, S and Melzow, FS and Wiegand, A and Kanzow, P and Rau, A and Kindler, S and Kocher, T}, title = {Vaccination rate and symptoms of long COVID among dental teams in Germany.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13654}, pmid = {40254623}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control/diagnosis ; Germany/epidemiology ; Male ; Female ; Adult ; *Vaccination/statistics & numerical data ; SARS-CoV-2/isolation & purification ; Middle Aged ; Dentists/statistics & numerical data ; Surveys and Questionnaires ; *COVID-19 Vaccines/administration & dosage ; Dental Hygienists/statistics & numerical data ; }, abstract = {Although COVID-19 is no longer a global public health threat, its consequences persist, with long COVID affecting at least 10% of patients and manifesting in various organ systems. National and international health agencies promoted vaccination to enhance population immunity, prioritizing healthcare personnel due to their high occupational risk. In a previous study, we found that the risk of SARS-CoV-2 transmission among dental teams in Germany was not higher than in the general population. This follow-up investigation aims to assess the vaccination status and the prevalence and severity of long COVID symptoms among dental teams in Germany. As part of a follow-up investigation involving the original cohort, 267 team members from 186 German dental practices previously included in the initial study completed an online questionnaire. The questionnaire covered three topics: (1) vaccination status, (2) confirmed COVID-19 diagnosis, and (3) self-reported long COVID symptoms. One hundred and seventy-two dentists (64.4%), 74 dental assistants (27.7%) and 21 dental hygienists (7.9%) completed the questionnaire. In total, 245 participants (91.8%) were at least once vaccinated. A COVID-19 infection after January 1st 2021 was reported by 146 (54.7%) participants, of which 33 participants (22.6%) suffered from long COVID symptoms. Our results showed lower vaccination rates among dental auxiliary personnel compared to dentists (95.9% vs. 84.2%). Individuals with long COVID symptoms were more often dental assistants (48.5% vs. 29.2%) or dental hygienists (15.2% vs. 8.0%) than dentists (36.4% vs. 62.8%) compared to the group not reporting long COVID symptoms (p = 0.025). In addition, it is unlikely that dental healthcare personnel are more prone to experiencing more severe symptoms compared to the general population. Vaccination against SARS-CoV-2 is likely to help against symptoms of long COVID.}, } @article {pmid40254579, year = {2025}, author = {Ewing, AG and Joffe, D and Blitshteyn, S and Brooks, AES and Wist, J and Bar-Yam, Y and Bilodeau, S and Curtin, J and Duncan, R and Faghy, M and Galland, L and Pretorius, E and Salamon, S and Buonsenso, D and Hastie, C and Kane, B and Khan, MA and Lal, A and Lau, D and MacIntyre, R and McFarland, S and Munblit, D and Nicholson, J and Ollila, HM and Putrino, D and Rosario, A and Tan, T and , }, title = {Long COVID clinical evaluation, research and impact on society: a global expert consensus.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {24}, number = {1}, pages = {27}, pmid = {40254579}, issn = {1476-0711}, mesh = {Humans ; *COVID-19/diagnosis/therapy/complications/epidemiology ; Consensus ; SARS-CoV-2 ; Delphi Technique ; Post-Acute COVID-19 Syndrome ; Global Health ; Child ; }, abstract = {BACKGROUND: Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.

METHODS: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.

RESULTS: The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

CONCLUSIONS: This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.}, } @article {pmid40253365, year = {2025}, author = {Vieira, YP and da Silva, LN and Nunes, BP and Gonzalez, TN and Duro, SMS and de Oliveira Saes, M}, title = {Relationship between long covid and functional disability in adults and the seniors in the south of Brazil.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {1458}, pmid = {40253365}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Cross-Sectional Studies ; Brazil/epidemiology ; Female ; *Activities of Daily Living ; Middle Aged ; Aged ; Adult ; *Persons with Disabilities/statistics & numerical data ; Disability Evaluation ; SARS-CoV-2 ; Aged, 80 and over ; }, abstract = {BACKGROUND: Individuals living with long COVID experience a range of symptoms that affect their ability to carry out daily activities or participate in social and community life. This study aimed to analyze association between functional disability and the occurrence of long COVID symptoms, as well as to analyze the effect of symptom persistence time on functional disability.

METHODS: This is a cross-sectional study using data from the SulCovid-19 study, which interviewed individuals who had COVID-19 between December 2020 and March 2021. The functional disability outcome was assessed using the Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales, while the exposures were the symptoms of long COVID. Adjusted analyses between outcomes and exposures, stratified by time after the acute phase of infection, were performed using Poisson regression with robust variance adjustment.

RESULTS: The prevalence of BADL disability was 4.8% (95%CI 4.0;5.6), and for IADL disability, it was 8.4% (95%CI 7.4;9.4). The main symptoms associated with BADL disability were dyspnea, dry cough and sore throat, while for IADL, they were joint pain, muscle pain, loss of sensation, nasal congestion, sore throat and runny nose. When stratified by tertiles of time after the acute phase of infection, a relationship was found between BADL disability and dyspnea, ageusia and, nasal congestion in the 3rd tertile, while only ageusia was found to be related to IADL disability in the 3rd tertile.

CONCLUSIONS: Long COVID symptoms were associated wiht limitations in the functional capacity of adults and the seniors. The findings can be used to guide the care and rehabilitation of individuals with disabilities who have had COVID-19, particularly for referral to appropriate health professionals.}, } @article {pmid40251531, year = {2025}, author = {Bonfim, LPF and Oliveira, CRA and Correa, TR and Kopittke, L and Teixeira, AL and Marcolino, MS}, title = {Persistent cognitive symptoms in mild COVID-19 infection: a retrospective cohort study.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {555}, pmid = {40251531}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; Female ; Male ; Retrospective Studies ; Middle Aged ; Brazil/epidemiology ; Adult ; Aged ; SARS-CoV-2 ; Telemedicine ; *Cognitive Dysfunction/epidemiology ; }, abstract = {BACKGROUND: The COVID-19 pandemic represented a healthcare challenge of unparalleled magnitude worldwide. As patients recovered from the acute infection, a new challenge emerged, i.e., the development of post-acute symptoms. The main goal of this study was to evaluate the trajectory of cognitive symptoms since the acute phase of COVID-19 among patients followed through a telehealth program in Brazil.

METHODS: A retrospective cohort study was conducted with confirmed COVID-19 patients followed by a Brazilian telehealth program who presented cognitive symptoms in the acute phase of infection. The objective of the current analysis was to assess the persistence or remission of cognitive symptoms at 24 weeks after the onset of acute COVID-19 symptoms, as well as the factors associated with such manifestations. The study used chi-square tests and multivariate logistic regression models to assess the association between patients' parameters and the presence of cognitive symptoms. A backward stepwise method was applied to define significant characteristics, which were then evaluated using odds ratios and 95% confidence intervals.

RESULTS: Among 319 patients who had cognitive symptoms during acute COVID-19, 89 (27.9%) reported persistence of cognitive symptoms for more than 24 weeks from the acute onset of the infection. Female sex (OR 2.33 [95% CI 1.23-4.43]) and having been infected during the second wave of COVID-19 (OR 2.30 [95% CI 1.34-3.96]) were associated with the persistence of symptoms beyond 24 weeks.

CONCLUSIONS: Approximately one-third of patients with COVID-19, mainly women and people infected during the second wave of infection, experienced persistent cognitive symptoms.}, } @article {pmid40251050, year = {2025}, author = {Vieth, K and Hummers, E and Roder, S and Müller, F and Wegener, GS and Müllenmeister, C and El-Sayed, I and Königs, G and Schröder, D and Schmachtenberg, T}, title = {[How do people with long COVID cope with their symptoms and everyday limitations? A qualitative study with four focus groups].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.zefq.2025.03.005}, pmid = {40251050}, issn = {2212-0289}, abstract = {BACKGROUND: The heterogenous and fluctuating intensity of long COVID symptoms poses a challenge to both patients and healthcare providers due to a lack of causal treatment options. The aim of supportive therapies is to help individuals cope with symptoms in daily life and maintain functionality. This study aims to identify coping strategies employed by those affected by long COVID and their perceived benefits.

METHODS: A qualitative study was conducted with four focus groups comprising 23 adult patients suffering from long COVID. The recorded and transcribed group discussions were analyzed using content-structuring content analysis according to Kuckartz. The results were then systematically analyzed, interpreted, and put in a theoretical context.

RESULTS: Participants utilized healthcare resources but developed their own strategies for dealing with long COVID because of their dissatisfaction with medical care. These strategies included energy and resource management, physical activity, enhancing health literacy, changing mindset and lifestyle, infection prevention, using medical aids, and dietary changes.

CONCLUSIONS: This study demonstrates that people with long COVID employ a variety of strategies to cope with impairments in everyday life. According to the interviewees, integrating these approaches into the treatment of long COVID can help to reduce the burden of symptoms on those affected, restore their everyday functionality, and improve their self-efficacy and quality of life. Established concepts like "pacing" or "shared-decision making" can serve as a starting point for developing individualized coping strategies and treatment concepts together with patients.}, } @article {pmid40250803, year = {2025}, author = {Hatakeyama, J and Nakamura, K and Kanda, N and Kawauchi, A and Fujitani, S and Oshima, T and Kato, H and Ota, K and Kamijo, H and Asahi, T and Muto, Y and Hori, M and Iba, A and Hosozawa, M and Iso, H}, title = {Long-term functional prognosis with tocilizumab in severe COVID-19 infection: A multicenter prospective observational study on mechanically ventilated ICU patients in the COVID-19 Recovery Study II.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {}, number = {}, pages = {102708}, doi = {10.1016/j.jiac.2025.102708}, pmid = {40250803}, issn = {1437-7780}, abstract = {BACKGROUND: Tocilizumab, an IL-6 receptor antagonist, may prevent functional impairments in critically ill patients by attenuating the cytokine storm. This study investigated a potential effect of tocilizumab on preventing functional impairments in patients with severe coronavirus infection 2019 (COVID-19).

METHODS: In a multicenter prospective observational study, patients with COVID-19 ≥20 years requiring mechanical ventilation admitted to the intensive care unit between April 2021 and September 2021 and discharged alive were followed for one year. A self-administered questionnaire on sequelae and functional impairments was mailed in August 2022, and data were collected. A multivariate logistic regression was used to assess the impact of tocilizumab on physical function, mental health, and Long COVID.

RESULTS: Of 157 analyzed patients, 41 received tocilizumab. The tocilizumab group had more severe illness, but a lower prevalence of physical impairment (17.1% vs. 23.3%, p = 0.41) and mental disorders (19.5% vs. 39.7%, p = 0.009) than the non-tocilizumab group. The prevalence of Long COVID was higher in the tocilizumab group (92.7% vs. 80.2%, p = 0.06), whereas fatigue/malaise was significantly lower (19.5% vs. 37.1%, p = 0.039). Adjusted odds ratios (95% confidence interval) for physical impairment, mental disorders, and Long COVID with tocilizumab were 0.70 (0.2 to 2.1), 0.40 (0.16 to 1.01), and 2.94 (0.7 to 12.3), respectively, with no significant difference.

CONCLUSIONS: Tocilizumab was associated with a lower prevalence of physical impairment and mental disorders at 1 year in patients with severe COVID-19. Furthermore, Long COVID had a weaker impact on physical and cognitive functions.}, } @article {pmid40250063, year = {2025}, author = {Hibino, K and Ariie, T}, title = {Letter to the editor regarding: "Effectiveness of a 12-week telerehabilitation training in people with long COVID: A randomized controlled trial".}, journal = {Annals of physical and rehabilitation medicine}, volume = {68}, number = {4}, pages = {101957}, doi = {10.1016/j.rehab.2025.101957}, pmid = {40250063}, issn = {1877-0665}, } @article {pmid40250060, year = {2025}, author = {Lai, CY and Lin, CH and Chiang, SL}, title = {Response to comment on "Effectiveness of a 12-week telerehabilitation training in people with long COVID: A randomized controlled trial".}, journal = {Annals of physical and rehabilitation medicine}, volume = {68}, number = {4}, pages = {101975}, doi = {10.1016/j.rehab.2025.101975}, pmid = {40250060}, issn = {1877-0665}, } @article {pmid40249096, year = {2025}, author = {Uhlig-Reche, H and Rolin, S and Karnik, R and Lyons, M and Verduzco-Gutierrez, M}, title = {Compassion fatigue, work engagement, and psychological distress in health care workers treating patients with long COVID.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1002/pmrj.13383}, pmid = {40249096}, issn = {1934-1563}, abstract = {BACKGROUND: Health care workers (HCWs) caring for patients with chronic disease are more likely to experience compassion fatigue. The impacts on HCWs caring for patients with a new complex chronic disease, long COVID, are unknown.

OBJECTIVE: To measure compassion fatigue, work engagement, and psychological distress in HCWs caring for patients with long COVID and investigate associations with personal history of long COVID and demographic and occupational characteristics.

DESIGN: Cross-sectional survey study assessing demographic and occupational characteristics, Compassion Fatigue-Short Scale (CF-SS), Utrecht Work Engagement Scale-3 (UWES-3), and Screening Tool for Psychological Distress (STOP-D) in HCWs caring for patients with long COVID.

SETTING: Online survey from March-June 2023.

PARTICIPANTS: 116 HCWs caring for patients with long COVID.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: CF-SS, UWES-3, and STOP-D scores and associations with personal history of long COVID, demographic and occupational factors.

RESULTS: HCWs with a personal history of long COVID had worse scores in all outcome measures compared to those without long COVID. Effects were moderate (UWES-3: η[2] = -0.09, p = .01; STOP-D: η[2] = 0.06, p = .02; CF-SS: η[2] = 0.07, p = .02). Outcome measures were comparable between physical medicine and rehabilitation physicians and other HCWs (p > .05). CF-SS showed a small positive correlation (rs = 0.19, n = 112, p = .04) with the percentage of the provider's patient population with long COVID. Mean outcome measures differed between career-level groups with medium to large effects (UWES-3: η[2] = 0.13, STOP-D: η[2] = 0.06, CF-SS: η[2] = 0.06). Work engagement was worse in early career compared to late career (p  <.01). Psychological distress was worse in middle career compared to late career (p = .02). Compassion fatigue was worse in early career compared to late career (p = .02).

CONCLUSIONS: Among HCWs caring for patients with long COVID, mean scores for all primary outcomes were worse in HCWs with a personal history of long COVID compared to those without. Early career HCWs caring for this population are less engaged and experience greater compassion fatigue whereas those in middle career experience greater psychological distress.}, } @article {pmid40248705, year = {2025}, author = {Scott, JM and Qiu, Z and Rahman, J and Moskowitz, CS and Michalski, MG and Lehman, S and Lee, CP and Harrison, J and Yu, AF and Marouf, A and Vardhana, S and Boutros, PC and Jones, LW}, title = {Case Report: Decentralized trial of tolerability-adapted exercise therapy after severe Covid-19.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1529385}, pmid = {40248705}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/therapy/immunology ; *Exercise Therapy/methods/adverse effects ; *SARS-CoV-2 ; Male ; Middle Aged ; Female ; Aged ; Quality of Life ; Prospective Studies ; Treatment Outcome ; }, abstract = {We assessed the safety, tolerability, and effects of exercise therapy in three patients with cancer and hospitalization for SARS-CoV-2 infection in an early-phase prospective trial. All study assessments and exercise sessions were conducted remotely (decentralized) in patient's homes. Patients received five escalated doses of aerobic exercise therapy (range, 90 to 375 minutes per week) following a tolerability-based adapted schedule over 30 consecutive weeks. Exercise therapy was safe (i.e., no serious adverse events), tolerable (i.e., all exercise therapy doses were completed, with an overall average relative exercise dose intensity of 89%), and associated with improvements in patient physiology (e.g., exercise capacity) and patient-reported outcomes (e.g., quality of life). Correlative proteomic and single-cell immune sequencing of peripheral blood samples revealed marked alterations in protein and immune phenotypes implicated in post COVID-19 condition. (ClinicalTrials.gov number, NCT04824443).}, } @article {pmid40248479, year = {2025}, author = {Gong, KD and Afshar, AS and Brown, F and Alavi, R and Ganesh, R and Kharrazi, H}, title = {Assessing the Impact of Post-COVID Clinics on 6-Month Health Care Utilization for Patients With Long COVID: A Single-Center Experience.}, journal = {Mayo Clinic proceedings. Innovations, quality & outcomes}, volume = {9}, number = {3}, pages = {100603}, pmid = {40248479}, issn = {2542-4548}, abstract = {OBJECTIVE: To assess the impact of post-COVID clinics by examining the association between their early usage and downstream health care utilization.

PATIENTS AND METHODS: In a case-control study spanning data from March 11, 2020 to June 1, 2023, patients with Long COVID were identified from a major health system using diagnosis codes. The Fast, Large-Scale Almost Matching Exactly algorithm was used to match patients who presented early to post-COVID clinics with patients with Long COVID who did not attend such clinics. Matching was performed on demographic characteristics, acute COVID severity, comorbidities, diagnosis date, and vaccination, to reduce confounders for the comparison of the health care utilization and mortality between cohorts.

RESULTS: When exactly matching on all 46 features, the algorithm yielded 2814 matched patients, of whom 692 (24.6%; 66.6% females; mean [SD] age, 48.8 [14.5] years) were seen in post-COVID clinics within the first 6 months and 2122 (75.4%; 64.1% females; mean [SD] age, 49.7 [15.2] years) who were not. The average treatment effect (95% CI) of early post-COVID clinic usage was -0.60 (-0.83 to -0.39) on inpatient visits, -0.19 (-0.26 to -0.11) on emergency department visits, 7.62 (6.96-8.56) on outpatient visits, -$3467 (-$6267 to -$754) on estimated costs, and -0.006 (-0.010 to -0.003) on mortality.

CONCLUSION: Early usage of post-COVID clinics by patients with Long COVID is associated with not only fewer downstream inpatient stays, emergency department visits, estimated costs, and reduced mortality within the first 6 months but also greater outpatient utilization. Results suggest early post-COVID clinic involvement shifts care to outpatient settings, potentially reducing costs and mortality.}, } @article {pmid40247373, year = {2025}, author = {Cruz, T and Albacar, N and Ruiz, E and Lledo, GM and Perea, L and Puebla, A and Torvisco, A and Mendoza, N and Marrades, P and Sellares, J and Agustí, A and Viñas, O and Sibila, O and Faner, R}, title = {Persistence of dysfunctional immune response 12 months after SARS-CoV-2 infection and their relationship with pulmonary sequelae and long COVID.}, journal = {Respiratory research}, volume = {26}, number = {1}, pages = {152}, pmid = {40247373}, issn = {1465-993X}, support = {ID 100010434, LCF/BQ/PI22/11910042//'la Caixa' Foundation/ ; }, mesh = {Humans ; *COVID-19/immunology/complications/blood/diagnosis ; Male ; Female ; Middle Aged ; Aged ; Autoantibodies/blood ; SARS-CoV-2/immunology ; Time Factors ; Adult ; *Lung/immunology/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Most patients recover fully after an acute infection by SARS-CoV-2. Some, however, may develop pulmonary sequelae (PS) and/or long COVID (LC). However, whether these two clinical conditions have similar or different pathogenic mechanisms is unknown.

METHODS: The levels of autoantibodies and 184 inflammatory and organ damage associated proteins in plasma were determined (by immunofluorescence and Olink panels, respectively) 1 year after an acute infection by SARS-CoV-2 in 51 patients with PS (DLCO < 80% ref), 31 patients with LC and 31 patients fully recovered (Rec). PS was defined by the presence of reduced carbon monoxide diffusing capacity (DLCO) lower than 80% ref. LC was defined by the presence of chronic symptoms in the absence of an alternative diagnosis.

RESULTS: We found that patients with PS or LC both showed increased levels than Rec of anti-microbial, immune cell activation and recruitment related proteins. Patients with PS showed higher levels of anti-nuclear autoantibodies, whereas LC patients had increased levels of organ-damage associated proteins. In patients with PS most of the elevated proteins correlate with the impairment of lung function (DLCO). Finally, in PS we additionally performed the determinations at an earlier time point (6 months) and showed that the expression of CCL20 and IFN-ɣ was already higher at 6 months, while CCL3 and CCL19 increase from 6 to 12 months, suggesting a pathogenic role in PS persistence.

CONCLUSIONS: Patients with PS or LC have abnormal but different persistent circulatory immune and organ damage biomarkers, suggesting different underlying biology of both post-COVID conditions.}, } @article {pmid40246685, year = {2025}, author = {}, title = {Correction to: Impact of intravenous laser irradiation of blood on cognitive function and molecular pathways in long COVID patients: a pilot study.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {}, number = {}, pages = {}, doi = {10.1093/qjmed/hcaf083}, pmid = {40246685}, issn = {1460-2393}, } @article {pmid40246350, year = {2025}, author = {Rubio-Casillas, A and Rodríguez-Quintero, CM and Hromić-Jahjefendić, A and Uversky, VN and Redwan, EM and Brogna, C}, title = {The essential role of prebiotics in restoring gut health in long COVID.}, journal = {Progress in molecular biology and translational science}, volume = {213}, number = {}, pages = {385-411}, doi = {10.1016/bs.pmbts.2025.01.004}, pmid = {40246350}, issn = {1878-0814}, mesh = {Humans ; *Prebiotics/administration & dosage ; *COVID-19/microbiology/immunology ; *Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis/microbiology ; Probiotics ; Pandemics ; }, abstract = {The gut microbiota (GM) plays an essential role in human health, influencing not only digestive processes but also the immune system´s functionality. The COVID-19 pandemic has highlighted the complex interaction between viral infections and the GM. Emerging evidence has demonstrated that SARS-CoV-2 can disrupt microbial homeostasis, leading to dysbiosis and compromised immune responses. The severity of COVID-19 has been associated with a reduction in the abundance of several beneficial bacteria in the gut. It has been proposed that consuming probiotics may help to re-colonize the GM. Although probiotics are important, prebiotics are essential for their metabolism, growth, and re-colonization capabilities. This chapter delves into the critical role of prebiotics in restoring GM after COVID-19 disease. The mechanisms by which prebiotics enhance the metabolism of beneficial bacteria will be described, and how prebiotics mediate the re-colonization of the gut with beneficial bacteria, thereby restoring microbial diversity and promoting the resilience of the gut-associated immune system. The benefits of consuming prebiotics from natural sources are superior to those from chemically purified commercial products.}, } @article {pmid40246346, year = {2025}, author = {Adilović, M}, title = {COVID-19 related complications.}, journal = {Progress in molecular biology and translational science}, volume = {213}, number = {}, pages = {259-314}, doi = {10.1016/bs.pmbts.2025.02.002}, pmid = {40246346}, issn = {1878-0814}, mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; Pregnancy ; Pandemics ; Female ; }, abstract = {The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.}, } @article {pmid40244965, year = {2024}, author = {Boucher, C and Glatt, S and Silver, C and Chennapragada, L and Sullivan, S and Dichiara, A and Sokol, Y and Patel, S and Goodman, M}, title = {A qualitative analysis of lived experiences, mental health treatment needs, and psychotherapeutic applications among veterans with long COVID.}, journal = {Psychological services}, volume = {}, number = {}, pages = {}, doi = {10.1037/ser0000925}, pmid = {40244965}, issn = {1939-148X}, support = {//US Department of Veterans Affairs; Veteran Affairs Research Department/ ; }, abstract = {Long COVID remains a pressing health concern among Americans, with current data suggesting that 45% of those infected by COVID-19 experience at least one symptom of Long COVID. Veterans are a particularly at-risk population due to their unique demographic characteristics and lived experiences. Despite this, there has been a lack of treatment development for Long COVID that targets mental health symptoms and is veteran specific. There is a need for effective treatments to help veterans cope with a Long COVID diagnosis and recovery. This quality improvement project aims to gain insight into the lived experiences and mental health needs of veterans with Long COVID to help inform future treatment development. A sample of 21 veterans (57% male, 67% Black, 43% Hispanic) participated in qualitative interviews where they were asked 23 questions about their experiences living with Long COVID and seeking medical treatment, as well as their ongoing mental health needs. Qualitative data were extracted from these interviews and analyzed. Four main themes were identified: interpersonal concerns and challenges with social interaction; difficulties with day-to-day living; barriers and facilitators to accessing medical treatment; and mental health effects and attitudes toward psychotherapy. Veterans described significant impairments in functioning, as well as feelings of isolation and loneliness. These findings demonstrate the need for a psychotherapeutic intervention that can facilitate interpersonal connection, improve functioning, and decrease psychiatric symptoms. (PsycInfo Database Record (c) 2025 APA, all rights reserved).}, } @article {pmid40243865, year = {2025}, author = {Dos Reis, GG and Silvestre, RT and Alves, G and Delmonico, L and Chantre-Justino, M and Moreira, ADS and Müller, BLA and do Nascimento, CR and da Silva, DLP and Dos Santos, LS and Mattos-Guaraldi, AL and Ornellas, MH}, title = {Leukocyte telomere length and telomerase activity in Long COVID patients from Rio de Janeiro, Brazil.}, journal = {Memorias do Instituto Oswaldo Cruz}, volume = {120}, number = {}, pages = {e240129}, pmid = {40243865}, issn = {1678-8060}, mesh = {Humans ; *Telomerase/blood/metabolism ; *COVID-19/enzymology ; Male ; Female ; *Leukocytes/enzymology ; *Telomere/genetics ; Middle Aged ; Brazil ; Real-Time Polymerase Chain Reaction ; Adult ; SARS-CoV-2 ; Case-Control Studies ; Aged ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the new coronavirus 2 (severe acute respiratory syndrome coronavirus 2 - SARS-CoV-2). Long COVID is a new condition associated with persistent COVID-19 symptoms and/or new emerging symptoms. Telomeres are specialised structures for genome protection at the end of chromosomes and telomerase is the enzyme that synthesises telomere DNA.

OBJECTIVES: Patients with Long COVID symptoms were recruited at the Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, Brazil, with the main purpose of investigating the association between telomere length and Long COVID.

METHODS: Leukocyte telomere length (LTL) was determined by quantitative real-time polymerase chain reaction (qPCR) in 34 Long COVID patients compared to a control group (n = 122). Telomerase activity was determined by qPCR assays using the commercial kit from ScienCell. A questionnaire on symptoms, vaccine doses and blood count was completed.

FINDINGS: The Long COVID patients were found to have an increase in LTL. Telomerase activity was also examined in a smaller number of patients and found to be reactivated in the blood.

MAIN CONCLUSIONS: It will be necessary to conduct further studies and monitor Long COVID patients to determine if future health issues could be linked to telomerase activity and elongated telomeres.}, } @article {pmid40242142, year = {2024}, author = {Cherif, H and Mokaddem, S and Debiche, S and Kalboussi, S and Yangui, F and Charfi, MR}, title = {Incidence and predictive factors of hyperventilation syndrome in patients after COVID 19 pneumonia: a prospective cohort study.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {1497}, pmid = {40242142}, issn = {2046-1402}, mesh = {Humans ; Male ; *COVID-19/complications/epidemiology ; Female ; Middle Aged ; Incidence ; Prospective Studies ; Aged ; *Hyperventilation/epidemiology/etiology ; Adult ; SARS-CoV-2 ; Stress Disorders, Post-Traumatic/epidemiology ; Risk Factors ; Comorbidity ; Syndrome ; }, abstract = {BACKGROUND: This study investigates the incidence and predictive factors of Hyperventilation Syndrome (HVS) in patients after COVID 19 pneumonia, addressing the clinical overlap between these conditions.

METHODS: A one-month prospective study was conducted, tracking survivors of COVID-19 pneumonia. Patients were evaluated for ongoing clinical status, including HVS and post-traumatic syndrome disorder (PTSD), using clinical questionnaires, mMRC, Post-COVID-19 Functional Status (PCFS) Score, Nijmegen score, and PTSD Checklist for DSM-5 questionnaire.

RESULTS: Our study included 222 patients (median age: 57 years, male predominance 62.6%). Somatic comorbidities, primarily metabolic disorders, were reported in 71.2% of cases. The majority had severe or critical infection forms (78.4%), and 91.9% experienced acute symptoms, with 86.5% having three or more symptom clusters. At one month follow-up, dyspnea (52.9%) and asthenia (21.7%) persisted. Functional limitations (PCFS Grade > 2) were observed in 19.6% of patients. The overall incidence of HVS was 158 per 1000 patients, and PTSD was 445 per 1000 patients. Multivariate logistic regression identified cognitive impairment (acute phase), persistent weight loss (post-COVID-19 phase), PCFS grade > 2, and PTSD as independent factors for developing HVS, with relative risks (RRs) of 3.47 (95%CI [1.48-8.31]; p = 0.004), 11.87 (95%CI [1.25-112.88]; p = 0.031), 3.24 (95%CI [1.34-7.86]; p = 0.009), and 5.98 (95%CI [2.27-15.77]; p < 0.001), respectively.

CONCLUSION: HVS is prevalent in the post-COVID-19 phase, affecting 15.6 % of survivors. Identified predictive factors suggest the convergence of psychosomatic pathophysiological mechanisms. Further research is crucial for a detailed understanding of these mechanisms in long COVID-19 patients.}, } @article {pmid40241147, year = {2025}, author = {Morello, R and De Rose, C and Martino, L and Raffaelli, F and Zampino, G and Valentini, P and Buonsenso, D}, title = {Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review.}, journal = {Italian journal of pediatrics}, volume = {51}, number = {1}, pages = {119}, pmid = {40241147}, issn = {1824-7288}, mesh = {Humans ; *Dietary Supplements ; Retrospective Studies ; *COVID-19/complications ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID Condition (PCC), emerging as a significant long-term consequence of SARS-CoV-2 infection, affects not only adults but also the pediatric population. Despite ongoing research, the precise pathophysiology of PCC remains elusive. However, several putative mechanisms have been identified, leading to the exploration of various therapeutic strategies. Notably, in the adult population, there has been substantial interest in the potential efficacy of nutritional supplements. Regrettably, information regarding the use of such supplements in the pediatric population is currently lacking.

METHODS: The present study was conducted to assess the impact of nutritional supplements on alleviating long COVID symptoms in children. To achieve this, we conducted a retrospective analysis of nutrient supplements administered by parents to children with Post-COVID Condition (PCC) between February 2020 and October 2022. Statistical analyses were employed to determine associations between categorical variables.

RESULTS: A total of 1243 children were enrolled following documented SARS-CoV-2 infection, with 940 (76.2%) diagnosed as recovered and 294 (23.8%) diagnosed with Long COVID. Among Long COVID patients experiencing disabling symptoms, treatment with oral lactoferrin and/or a Multi-Element Product (MEP) with antioxidant and anti-inflammatory properties was initiated. The correlation analysis between the use of supplements and persistence of long COVID at the next follow-up showed that the use of MEP alone (OR 5.7, 95% CI 3.8-8.5), or the combination of MEP and lactoferrin (OR 5.06, 95% CI 3.3-7.6) three months after the initial infection and for the following three months, were associated with a lower risk having long covid at six months following initial infection, when compared with the use of lactoferrin alone (OR 7.6 95% CI 5.1-11.4).

CONCLUSIONS: This proof-of-concept study revealed that MEP and lactoferrin, when administered three months after initial infection in patients with a new diagnosis of long covid, may have a positive impact on improving Long COVID symptoms in children during follow-up evaluations. This positive trend toward reducing Post-COVID Condition (PCC) exhibited by MEP and lactoferrin suggested a potential benefit worthy of exploration in future randomized controlled trials.}, } @article {pmid40240378, year = {2025}, author = {Vieira, YP and Rocha, JQS and Dos Santos Ferreira Viero, V and Nunes, BP and Facchini, LA and Duro, SMS and Neves, RG and Fernández-de-Las-Peñas, C and de Oliveira Saes, M}, title = {Dose-response effect between the number of long COVID symptoms and the use of different health services.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13104}, pmid = {40240378}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications/therapy ; Male ; Female ; Brazil/epidemiology ; Middle Aged ; Adult ; Cross-Sectional Studies ; SARS-CoV-2/isolation & purification ; Primary Health Care/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Aged ; *Health Services/statistics & numerical data ; }, abstract = {This study aims to identify the use of health services by individuals with long COVID residing in South Brazil 6 months after the acute phase of a SARS-CoV-2 infection. A cross-sectional cohort study of individuals who survived coronavirus disease was conducted in Rio Grande, Brazil. The participants were asked about their use of health services during the 6-10 months following recovery from SARS-CoV-2 infection. Data on the overall use of primary healthcare services, general practitioner services, emergency services, specialist doctors' services, and specialized services were collected. Individuals with long COVID reported more frequent use of primary healthcare services, emergency services, specialist doctors' services, and specialized services than those without long COVID. The musculoskeletal, neurological, and respiratory symptoms of long COVID were associated with frequent use of primary healthcare services, whereas the neurological, digestive, and respiratory symptoms were associated with frequent use of emergency services. Finally, the use of specialist doctors' services and specialized services was more frequent in participants with neurological symptoms than in those without these symptoms. Individuals with long COVID used more healthcare services than those without long COVID in South Brazil. Participants with a greater number of symptoms used more health services than those with fewer symptoms. Healthcare services use depends on the type of the long COVID symptoms. Health services in Brazil need to be reorganized and adapted to provide adequate treatment and care to people with long COVID.}, } @article {pmid40239863, year = {2025}, author = {Schamess, A and Velten, M and Friedberg, A}, title = {Long COVID in 2025: a clinical viewpoint.}, journal = {Life sciences}, volume = {}, number = {}, pages = {123633}, doi = {10.1016/j.lfs.2025.123633}, pmid = {40239863}, issn = {1879-0631}, } @article {pmid40236471, year = {2024}, author = {McAllister, K}, title = {Contextualising Long Covid: Viral Sequelae, 'Post-Encephalitis' Lethargica and the Modern British Healthcare System, c. 1918-1945.}, journal = {Social history of medicine : the journal of the Society for the Social History of Medicine}, volume = {37}, number = {4}, pages = {737-757}, doi = {10.1093/shm/hkae052}, pmid = {40236471}, issn = {0951-631X}, abstract = {In the months after March 2020, people across Britain began to seek medical attention for protracted illness following an infection with coronavirus disease 2019. Through the efforts of patients, these illnesses were eventually gathered into the diagnostic category of 'Long Covid' and therefore viewed as viral sequelae, in turn opening up the possibility for medical care and treatment in the British health system. This article adds to such patient-made knowledge of Long Covid through a comparative historical analysis with the problem of 'Post-Encephalitis' Lethargica (EL). In the early twentieth century, the viral sequelae of EL were parsed in line with and thus shaped by the binary divisions that were becoming used to structure healthcare in Britain. By telling this story of the past, this article provides a framework to understand if and how such administrative divisions within the National Health Service (NHS) might continue to inform perceptions of and responses to Long Covid in the present.}, } @article {pmid40235692, year = {2025}, author = {Radhakrishna, K and Holland, J and O'Keeffe, F and Gaynor, K and Kinsella, J and Bramham, J}, title = {Analysis of the A-B Neuropsychological Assessment Schedule as a Cognitive Screener for Long COVID.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82311}, pmid = {40235692}, issn = {2168-8184}, abstract = {Aim To determine the sensitivity and specificity of the psychometric measures of the A-B Neuropsychological Assessment Schedule (ABNAS) to aid screening of long COVID (LC). Methods The participants (N=235) were recruited from an online study of cognitive and psychological consequences of LC, involving individuals attending an LC service in an acute tertiary university hospital and a comparison sample of community controls.The ABNAS for LC, a patient-perceived assessment scale in relation to the challenges they had encountered from LC, was used to identify the specific psychometric measures implicated in LC. Results The optimal cut-off value for total ABNAS scores and its psychometric subsets were obtained from receiver operating characteristic (ROC) curves. The sensitivity of the total ABNAS score of ≥21.5 was 81.6% for LC, taken as a post-COVID functional status (PCFS)grade of ≥ 2 as true positives, with a specificity = 72.3%. The specificity of the ABNAS fatigue subscale score of ≥ 8.5 for LC was 87.2%, while its sensitivity was 66.7%. The sensitivity of the ABNAS mental slowing subscale score of ≥ 4.5 was 82.8%, and the specificity was 70.3%. Conclusion Total ABNAS scores and their psychometric subsets (fatigue and mental slowing) are sensitive and specific for LC.}, } @article {pmid40234933, year = {2025}, author = {Makovski, TT and Steichen, O and Rushyizekera, M and van den Akker, M and Coste, J}, title = {Relationship between multimorbidity, SARS-COV-2 infection and long COVID: a cross-sectional population-based French survey.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {222}, pmid = {40234933}, issn = {1741-7015}, mesh = {Humans ; Female ; France/epidemiology ; *COVID-19/epidemiology/complications ; Cross-Sectional Studies ; Male ; Middle Aged ; *Multimorbidity ; Adult ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; }, abstract = {BACKGROUND: Understanding the risks of COVID-19-related consequences for vulnerable groups such as people with multimorbidity is crucial to better tailor health care and public health measures. The main objective of this study was to explore the association between multimorbidity and WHO-defined post-COVID condition (PCC), while also considering the association with SARS-COV-2 infection given that the infection is a prerequisite of PCC.

METHODS: This population-representative cross-sectional study was conducted in the general adult population in mainland France between 29 August and 31 December 2022 (N = 1813). The analyses of the association between multimorbidity (defined as disease count and most prevalent dyads/triads) and PCC or SAR-COV-2 infection were adjusted for age, sex, socioeconomic variables and number of infections (for PCC only) using adjusted Poisson regression with robust variance.

RESULTS: The study population had a mean age (SD) of 53 (± 18.5) years, while 53.6% were women. The likelihood of SARS-COV-2 infection increased with disease count but was only significant for ≥ 4 diseases. Five dyads and one triad presented a higher risk; almost all included anxiety. The likelihood of PCC increased with disease count, prevalence ratios (PRs) (95% CI) for 1, 2-3 and ≥ 4 diseases versus 0 were 1.90 (1.16-3.13), 3.32 (2.07-5.35) and 5.65 (3.41-9.38), respectively, and for 19 of 26 most prevalent dyads and the triad. The association was strongest for cardiac rhythm disorder and either low back pain (PR (95%CI) 4.17 (2.03-8.53)) or anxiety (PR (95%CI) 3.73 (1.98-7.01)).

CONCLUSIONS: Multimorbidity, most frequently in combination with anxiety or low back pain, presented a significant association with PCC beyond that of SARS-CoV-2 infection underscoring the importance of implementing strategies to prevent and manage persistent symptoms in vulnerable groups.}, } @article {pmid40234823, year = {2025}, author = {Yan, D and Liu, Y and Chen, R and Zhou, L and Wang, C and Ma, AHY and Chen, X and Song, Q and Qian, G}, title = {Follow-up of long COVID based on the definition of WHO: a multi-centre cross-sectional questionnaire-based study.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {1412}, pmid = {40234823}, issn = {1471-2458}, support = {XGZ2301//Academy Level Project of the First Affiliated Hospital of Ningbo University/ ; Evaluation of the effect of traditional Chinese medicine on the elderly patients with severe coronavirus disease 2019//Zhejiang Province Traditional Chinese Medicine Science and Technology Project/ ; LTGG23H260002//Zhejiang Provincial Natural Science Foundation of China/ ; Y23H190011//Zhejiang Provincial Natural Science Foundation of China/ ; 2023QL055//Youth Science and Technology Innovation Leading Talent project of Ningbo/ ; }, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; Cross-Sectional Studies ; Surveys and Questionnaires ; Adult ; China/epidemiology ; Follow-Up Studies ; Aged ; World Health Organization ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Young Adult ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {BACKGROUND: Since long COVID has hindered people from normal life, it is essential to understand its full spectrum of manifestation. However, it was heterogeneous in the existing studies and few large-scale studies have been conducted on Asian populations. Here, we conducted a multi-centre questionnaire-based study among Chinese people to explore the long COVID based on the definition of WHO.

METHODS: During March 20, 2023 and June 18, 2023, individuals with a history of confirmed or self-reported SARS-CoV-2 infection were recruited from three hospitals to fill out the questionnaire for long COVID. Each symptom was assigned with 0 to 3 points based on their severity. And the long COVID score was a sum of these points of each symptom. The reporting rate, time trend and risk factors of long COVID stratified by different systems were explored.

RESULTS: 3,693 individuals were recruited for the study. The reporting rate of at least one persistent long COVID symptoms and symptoms impacting daily life was 30.2% (1,117) and 10.7% (394). Systemic symptoms (20.7%, 765) were most easily reported. The most common symptoms were fatigue (16.3%, 602), cough (6.3%, 234) and expectoration (5.5%, 203). The reporting rate of long COVID and long COVID score decreased over time during a 180-day follow-up period (P < 0.05). For long COVID, older age (OR: 1.63, 1.38-1.93), female (OR: 1.19, 1.03-1.38) and SARS-CoV-2 reinfection (OR: 3.56, 2.63-4.80) were risk factors; while number of COVID-19 vaccine doses (OR: 0.87, 0.81-0.94) was a protective factor. The use of traditional Chinese medicine (OR: 0.51, 0.37-0.71) was a protective factor for symptoms impacting daily life.

CONCLUSIONS: Early interventions should be taken to minimize the impact of long COVID, especially for the elderly, females and those with SARS-CoV-2 reinfection. COVID-19 booster vaccination might play a potential role in minimizing the impact of long COVID.}, } @article {pmid40234084, year = {2025}, author = {Taylor, OL and Treneman-Evans, G and Riley, M and Bond-Kendall, J and Pike, KC}, title = {How young people experienced long covid services: a qualitative analysis.}, journal = {BMJ paediatrics open}, volume = {9}, number = {1}, pages = {}, doi = {10.1136/bmjpo-2024-003206}, pmid = {40234084}, issn = {2399-9772}, mesh = {Humans ; *COVID-19/therapy/epidemiology/psychology ; Child ; Adolescent ; Female ; Qualitative Research ; Male ; England/epidemiology ; SARS-CoV-2 ; Health Services Accessibility ; Interviews as Topic ; }, abstract = {UNLABELLED: ΒACKGROUND: After the COVID-19 pandemic, children and young people (CYP) with long covid were managed in specialist clinics. However, there is limited research on how CYP who accessed long covid clinics experienced them.

METHODS: We aimed to evaluate how acceptable paediatric long covid services were to patients. Semi-structured qualitative interviews with 13 paediatric patients were used to understand the experiences of patients with long covid. Recruited participants were aged 11-17 years old, had a long covid diagnosis, and accessed specialist paediatric service in the Southwest of England from June 2022 to September 2023. Clinicians working in the long covid clinics identified CYP who were eligible and asked their consent to be contacted by a member of the study team. All participants who consented to be involved in the study were sampled. Thematic analysis was used to extract codes and themes from the data.

RESULTS: Four themes were reported. Accessing specialist clinics helped CYP to feel validated; they appreciated consulting with clinicians who were knowledgeable about long covid and empathetic. CYP found comfort in knowing other CYP were experiencing long covid. CYP wanted to be proactive in their long covid management, appreciating regular appointments and the opportunity to learn about their condition. CYP desired normality, and therefore sought flexible appointment times, online appointments and reasonable adjustments. CYP found the waiting times to access long covid services were too long.

CONCLUSIONS: Our results stress the importance to CYP of several features of the care received in the specialist clinics. These relate to the experiences of CYP with long covid but potentially extend to CYP with other conditions, particularly long-term and/or poorly understood conditions. The results support creating community-based support groups for CYP with long-term medical conditions, providing online flexible appointments, offering early reasonable adjustments for school and providing quicker access to specialist clinics.}, } @article {pmid40234052, year = {2025}, author = {Hermans, LE and Wasserman, S and Xu, L and Eikelboom, J}, title = {Long COVID prevalence and risk factors in adults residing in middle- and high-income countries: secondary analysis of the multinational Anti-Coronavirus Therapies (ACT) trials.}, journal = {BMJ global health}, volume = {10}, number = {4}, pages = {}, doi = {10.1136/bmjgh-2024-017126}, pmid = {40234052}, issn = {2059-7908}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/complications ; Adult ; Middle Aged ; Prevalence ; Risk Factors ; SARS-CoV-2 ; *Developed Countries/statistics & numerical data ; Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: During the recent COVID-19 pandemic, reports of long-term persistence or recurrence of symptoms after SARS-CoV-2 infection emerged, which are now collectively referred to as 'long COVID'. Most descriptions of long COVID originate from patients residing in high-income countries. We set out to characterise long COVID in a large-scale clinical trial that was conducted in low-middle, high-middle and high-income countries.

METHODS: The Anti-Coronavirus Therapies trials enrolled 6528 adult patients with symptomatic COVID-19 in Argentina, Brazil, Canada, Colombia, Ecuador, Egypt, India, Nepal, Pakistan, Philippines, Russia, Saudi Arabia, South Africa and the United Arab Emirates. Long COVID was defined as the presence of patient-reported symptoms at 180 days after enrolment. Multivariable logistic regression was used to evaluate associations of baseline characteristics with long COVID.

RESULTS: Of 4697 included participants, 1181 (25.1%) reported long COVID symptoms. The most frequently reported symptoms were sleeping disorders (n=601; 12.8%), joint pain (n=461; 9.8%), fatigue (n=410; 8.7%) and headaches (n=382; 8.1%). Long COVID prevalence was higher in participants from lower middle-income compared with high-income countries (29.8% (850/2854) vs 14.4% (102/706); adjusted OR (aOR) 1.53 (1.10 to 2.14); p=0.012). Prevalence also varied between participants of different ethnic backgrounds and was highest (36.1% (775/2145)) for patients of Arab/North African ethnicity. Patients requiring inpatient admission were at increased risk of long COVID (aOR: 2.04 (1.63 to 2.54); p<0.001). Other independent predictors of long COVID were male sex, older age and hypertension. Vaccination, prior lung disease, smoking and diabetes mellitus conferred protective effects.

CONCLUSION: Symptoms of long COVID are reported in a quarter of cases of symptomatic COVID-19 in this study and were significantly more prevalent in participants from countries with lower income status and in patients of Arab/North African ethnicity. Research to further assess the health burden posed by long COVID in low- and middle-income countries is urgently needed.}, } @article {pmid40232883, year = {2025}, author = {Rattanawijit, M and Samutpong, A and Apiwattanakul, N and Assawawiroonhakarn, S and Techasaensiri, C and Boonsathorn, S and Chaisavaneeyakorn, S}, title = {Rates, Risk Factors and Outcomes of Complications After COVID-19 in Children.}, journal = {The Pediatric infectious disease journal}, volume = {44}, number = {5}, pages = {449-454}, doi = {10.1097/INF.0000000000004649}, pmid = {40232883}, issn = {1532-0987}, support = {P-20-50966//the National Science and Technology Development Agency, Thailand, the Royal College of Pediatricians of Thailand and Pediatric Society of Thailand/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Child ; Child, Preschool ; Male ; Adolescent ; Female ; Infant ; Risk Factors ; Retrospective Studies ; Prospective Studies ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome/epidemiology/etiology ; Infant, Newborn ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to various complications, including multisystem inflammatory syndrome in children (MIS-C) and post-COVID-19 conditions (long COVID). This study aimed to determine the rates, risk factors and outcomes of MIS-C and long COVID in children previously diagnosed with COVID-19.

METHODS: This study was a combined retrospective and prospective cohort study. Patients 0-18 years of age diagnosed with COVID-19 or another respiratory virus infection were enrolled between October 2021 and April 2022. Demographic and clinical data were reviewed. Information on persisting symptoms and their impacts were recorded at 1-3, 3-6 and 6-12 months after infection. Laboratory investigations and chest imaging examinations were performed during follow-up. MIS-C and long COVID were defined according to the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) definitions.

RESULTS: A total of 618 patients were enrolled, comprising 437 (70.7%) with COVID-19 and 181 (29.3%) with another respiratory virus infection. At 1-3 months, the rate of persisting symptoms was 16.5% in patients with COVID-19, compared with 1.1% in patients with another respiratory virus infection. The rate of MIS-C was 0.7%. The rate of long COVID according to the CDC and WHO definitions were 20.4% and 13.0%, respectively. Respiratory systems were most affected in long COVID. Age 5-18 years, anosmia during COVID-19, history of pneumonia and infection during the delta and omicron waves were associated with long COVID in children.

CONCLUSIONS: Long COVID after COVID-19 in children is uncommon. Children with anosmia and a history of pneumonia during COVID-19 require follow-up for long COVID.}, } @article {pmid40231351, year = {2025}, author = {Le, GH and Kwan, ATH and Guo, Z and Dev, DA and Wong, S and Badulescu, S and Ceban, F and Teopiz, KM and Johnson, DE and Gill, H and Di Vincenzo, JD and Meshkat, S and Rhee, TG and Ho, R and Phan, L and Rosenblat, JD and Mansur, RB and Subramaniapillai, M and McIntyre, RS}, title = {Impact of Fatigue on Subjective and Objective Cognitive Functions in Persons with Post-COVID-19 Condition.}, journal = {Clinical nursing research}, volume = {}, number = {}, pages = {10547738251329412}, doi = {10.1177/10547738251329412}, pmid = {40231351}, issn = {1552-3799}, abstract = {Post-COVID-19 condition (PCC) is a serious debilitating condition that develops after the resolution of an acute infection of severe acute respiratory syndrome-associated coronavirus 2. Some commonly reported symptoms include fatigue and cognitive deficits. Multiple lines of evidence have indicated fatigue to be associated with cognitive deficits in the general population. Herein, we perform a secondary analysis of the effects of fatigue on subjective and objective cognition in persons with PCC using a generalized linear model. In this study, fatigue was measured using the Fatigue Severity Scale (FSS) and cognition was measured using the Digit-Symbol Substitution Test (DSST) and the Trails Making Test parts A and B (TMT-A/B). FSS had a statistically significant negative correlation with DSST and TMT-A/B scores. Fatigue serves as a possible target for the development of PCC therapeutics. Fatigue and cognition correlates should be further investigated for underlying neurobiological substrates in persons with PCC.}, } @article {pmid40231214, year = {2025}, author = {Serafini, RA and Frere, JJ and Giosan, IM and Nwaneshiudu, CA}, title = {SARS-CoV-2-induced sensory perturbations: A narrative review of clinical phenotypes, molecular pathologies, and possible interventions.}, journal = {Brain, behavior, & immunity - health}, volume = {45}, number = {}, pages = {100983}, pmid = {40231214}, issn = {2666-3546}, abstract = {BACKGROUND: The acute and post-acute sequelae of SARS-CoV-2 infection have been of great clinical interest since the inception of the COVID-19 pandemic. Despite a high prevalence of individuals with persistent symptoms, a wholistic view of the effects of SARS-CoV-2 on special sensory systems is lacking. Considering the significant impact of normal sensory function on quality of life, the goal of this review is to highlight unresolved issues related to SARS-CoV-2-associated insults to the sensory nervous system.

MAJOR FINDINGS: In this narrative review, we discuss the epidemiology of SARS-CoV-2-induced sensory perturbations, underlying pathological mechanisms, and possible therapeutic strategies across the olfactory, gustatory, somatosensory, visual, and auditory systems. Examined literature included studies with human biospecimens, human-derived cell lines, and naturally susceptible animal models, which highlighted evidence of persistent functional disruption in all sensory systems. SARS-CoV-2 infection was associated with persistent inflammation in the olfactory epithelium/bulb, somatosensory ganglia, and gustatory systems, long-term transcriptional perturbations in the sensory central nervous system and peripheral nervous system, and detectable degeneration/apoptosis in the gustatory and visual systems. Few studies have proposed evidence-based therapeutic strategies for attenuating specific sensory abnormalities after SARS-CoV-2 infection.

CONCLUSION: While the olfactory system, and to some extent the visual and somatosensory systems, have been more thoroughly investigated from symptomatology, behavioral and molecular perspectives, there is still an unmet need for the development of therapeutics to treat COVID-induced impairment of these systems. Further, additional attention must be placed on COVID-associated impairment of the gustatory, visual, and auditory systems, which lack detailed mechanistic investigations into their pathogenesis.}, } @article {pmid40230744, year = {2025}, author = {Gupta, A and Rajan, V and Aravindakshan, R and Sirisha, P}, title = {Unmasking the Long-Term Effects of COVID-19 With a Focus on Chronic Fatigue Syndrome: A Community-Based Study From India.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80597}, pmid = {40230744}, issn = {2168-8184}, abstract = {Background The COVID-19 pandemic has highlighted the enduring health burden of long COVID, scientifically termed the postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or PASC. Long COVID manifests as diverse symptoms affecting multiple organ systems, significantly impacting individuals globally, and especially underrepresented rural populations. Objective This study aimed to evaluate the prevalence of chronic fatigue syndrome (CFS) among laboratory-confirmed COVID-19 patients in rural India, focusing on identifying its predictors and the implications for healthcare systems in resource-limited settings. Methodology Retrospective data analysis was conducted on the follow-up visits of post-COVID-19 patients in the field practice area of AIIMS Mangalagiri, Nuthakki, Andhra Pradesh, India. The study involved 500 COVID-19 survivors diagnosed via reverse transcription polymerase chain reaction (RT-PCR) between 2023 and 2024. Data was collected via a semi-structured questionnaire to retrieve socio-demographic and clinical parameters, while CFS severity was assessed using a validated scoring system. Multivariable logistic regression and path analysis were used to examine the associations between the predictors of CFS. Results The prevalence of CFS was seen in 107 patients (21.4%; 95% CI: 18.01-25.22). Risk factors included older age (adjusted odds ratio or aOR: 15.90 for ≥60 years), female gender (aOR: 1.90), and comorbidities (aOR: 3.92). Common symptoms observed were fatigue in 180 (36%), joint pain in 185 (37%), and muscle pain in 182 (36.4%) patients. There was no significant association between vaccination and CFS. Conclusion The study underscores the substantial burden of post-COVID fatigue in rural populations, with female patients, older adults, and those with comorbidities being at greater risk. Tailored healthcare interventions and proactive post-COVID monitoring are critical to address this challenge. Future research should explore the underlying mechanisms and assess the role of vaccination in mitigating the post-COVID sequelae.}, } @article {pmid40230626, year = {2025}, author = {Musachia, J and Radosta, J and Ukwade, D and Rizvi, S and Wahba, R}, title = {Postacute Sequelae From SARS-CoV-2 at the University of Illinois Hospital and Clinics: An Examination of the Effects of Long COVID in an Underserved Population Utilizing Manual Extraction of Electronic Health Records.}, journal = {American journal of medicine open}, volume = {13}, number = {}, pages = {100095}, pmid = {40230626}, issn = {2667-0364}, abstract = {BACKGROUND: Although there has been a steady decrease in morbidity and mortality from the SARS-CoV-2 virus since the 2020-2021 period, thousands of Americans are still infected with the virus daily. Some proportion of these infected individuals will go on to develop postacute sequelae from SARS-CoV-2 (PASC, or Long COVID), manifesting symptoms 4 weeks or more after recovery from COVID-19. PASC and its underlying pathophysiology are still poorly described and understood. Although hundreds of peer-reviewed, published investigations on Long COVID exist, few have focused on underserved urban patient populations. Most of the published research has involved reviews of diagnostic codes from electronic health records, or responses to questionnaires.

METHODS: We sought to review Long COVID in an underserved population in Chicago, and to go beyond electronic health record reviews of diagnostic codes, utilizing in-depth chart reviews, gleaned via manual extraction, focusing on notations of care providers. We investigated which specific preexisting conditions, if any, might be associated with specific Long COVID symptomatology's, and if any preexisting conditions predicted Long COVID. Study participants included 204 Long COVID patients, 98 COVID-19-positive patients, and 104 healthy (no history of COVID-19 infection) patients from an inner-city health system caring for underserved communities, whose records were reviewed via manual data extraction from electronic health records, focusing on provider notes in patient charts.

RESULTS: Our Long COVID symptom frequencies were distinct compared to frequencies from other reviews that did not focus on underserved populations and done with medical records when only diagnostic codes are utilized. Preexisting medical conditions did not predict similar Long COVID symptomologies, save for the significant association between preexisting cough/dyspnea/pulmonary conditions and preexisting migraine/headache and their analogous Long COVID symptoms.

CONCLUSIONS: The odds of having Long COVID increased comparatively in subjects hospitalized with COVID-19, subjects with BMI >30, and female subjects.}, } @article {pmid40230529, year = {2025}, author = {Zhang, Y and Ye, G and Zeng, W and Zhu, R and Li, C and Zhu, Y and Li, D and Liu, J and Wang, W and Li, P and Fan, L and Wang, R and Niu, X}, title = {Segregation and integration of resting-state brain networks in a longitudinal long COVID cohort.}, journal = {iScience}, volume = {28}, number = {4}, pages = {112237}, pmid = {40230529}, issn = {2589-0042}, abstract = {Long COVID is characterized by debilitating fatigue, likely stemming from abnormal interactions among brain regions, but the neural mechanisms remain unclear. Here, we utilized a nested-spectral partition (NSP) approach to study the segregation and integration of resting-state brain functional networks in 34 patients with long COVID from acute to chronic phase post infection. Compared to healthy controls, patients with long COVID exhibited significantly higher fatigue scores and shifted the brain into a less segregated state at both 1 month and 3 months post infection. During the recovery of fatigue severity, there was no significant difference of segregation/integration. A positive correlation between network integration and fatigue was observed at 1 month, shifting to a negative correlation by 3 months. Gene Ontology analysis revealed that both acute and long-term effects of fatigue were associated with abnormal social behavior. Our findings reveal the brain network reconfiguration trajectories during post-viral fatigue progression that serve as functional biomarkers for tracking neurocognitive sequelae.}, } @article {pmid40228860, year = {2025}, author = {Delfino, C and Carcel, C and Lin, X and Muñoz-Venturelli, P and Naismith, SL and Woodward, M and Peters, R and Wijesuriya, N and Law, M and Harding, IH and Wang, X and Elliott, J and Leder, K and Hutchings, O and Stecher, X and Zoungas, S and Anderson, CS}, title = {STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER): study protocol for a randomised, open label clinical trial in patients with persistent neurological symptoms after COVID-19 infection.}, journal = {BMJ open}, volume = {15}, number = {4}, pages = {e089382}, doi = {10.1136/bmjopen-2024-089382}, pmid = {40228860}, issn = {2044-6055}, mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; *COVID-19/complications ; *Atorvastatin/therapeutic use ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Quality of Life ; Prospective Studies ; Randomized Controlled Trials as Topic ; Male ; Female ; *Nervous System Diseases/drug therapy ; Adult ; Middle Aged ; Multicenter Studies as Topic ; Cognition/drug effects ; }, abstract = {INTRODUCTION: Increasing awareness of the high frequency, wide spectrum and disabling nature of symptoms that can persist following COVID-19 infection has prompted the investigation of management strategies. Our study aims to determine the effectiveness of atorvastatin on cognitive function, physical activity, mood, health-related quality of life and features of neurovascular impairment and neuroinflammation in adults with ongoing neurological symptoms after COVID-19 infection.

METHODS AND ANALYSIS: The STatin TReatment for COVID-19 to Optimise NeuroloGical recovERy study is an ongoing international, investigator-initiated and conducted, multicentre, prospective, randomised, open label, blinded endpoint trial with fixed time points for outcome assessments. A total of 410 participants with long covid neurological symptoms were planned to be randomly assigned to either the intervention group to receive 40 mg atorvastatin for 12 months or to a control group of no treatment, on top of usual care.

ETHICS AND DISSEMINATION: This study protocol was designed, implemented and reported, in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice, the National Health and Medical Research Council of Australia, the National Statement on Ethical Conduct in Human Research and with the ethical principles laid down in the World Medical Association Declaration of Helsinki. Central ethics committee approval was obtained from Sydney Local Health District Royal Prince Alfred Hospital Ethics (No: X21-0113 and 2021/ETH00777 10) in Australia. Site-specific ethics committee approvals were obtained elsewhere before any local study activities. All participants provided written informed consent.

TRIAL REGISTRATION NUMBER: The study protocol is registered at Clinicaltrials.gov (NCT04904536).}, } @article {pmid40228859, year = {2025}, author = {Kjellberg, A and Hassler, A and Boström, E and El Gharbi, S and Al-Ezerjawi, S and Schening, A and Fischer, K and Kowalski, JH and Rodriguez-Wallberg, KA and Bruchfeld, J and Ståhlberg, M and Nygren-Bonnier, M and Runold, M and Lindholm, P}, title = {Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial.}, journal = {BMJ open}, volume = {15}, number = {4}, pages = {e094386}, doi = {10.1136/bmjopen-2024-094386}, pmid = {40228859}, issn = {2044-6055}, mesh = {Humans ; Female ; Double-Blind Method ; Male ; Middle Aged ; Adult ; *COVID-19/therapy/complications ; *Hyperbaric Oxygenation/methods ; *Quality of Life ; Sweden ; SARS-CoV-2 ; Treatment Outcome ; Adolescent ; Young Adult ; }, abstract = {OBJECTIVES: To evaluate if 10 sessions of hyperbaric oxygen treatments (HBOTs) improve short- and long-term health related quality of life, symptoms and physical performance in long covid patients compared with placebo.

DESIGN: Parallel, randomised, placebo-controlled, double-blind trial.

SETTING: Single-centre, university hospital, Sweden.

PARTICIPANTS: Previously healthy subjects aged 18-60 years, diagnosed with long covid were included. We excluded pregnant women, patients with RAND-36 (role limitations due to physical health (RP) and physical functioning (PF)) above 70, diabetes, hypertension and contraindications for HBOT.

INTERVENTIONS: Subjects were randomly assigned to 10 sessions of HBOT or sham (placebo) treatments over 6 weeks. HBOT involved 100% oxygen, 2.4 bar, 90 min, placebo medical air, 1.34-1.2 bar. Randomisation (1:1) was done electronically, in blocks stratified by sex and disease severity. Subjects and investigators were blinded to allocation.

Primary endpoints were changes from baseline in RAND-36 PF and RP at 13 weeks. Efficacy was analysed on an intention-to-treat basis. Harms were evaluated according to the actual treatment given.

RESULTS: Between 15 September 2021 and 20 June 2023, 80 subjects (65 women, 15 men) were enrolled and randomised (40 in each group). The trial is completed. The primary endpoint analysis included 79 subjects (40 in HBOT and 39 in control). At 13 weeks, both groups showed improvement, with no significant difference between HBOT and placebo in PF (least square mean difference between groups (LSD), 0.63 (95% CI -7.04 to 8.29), p=0.87) and RP (LSD, 2.35 (95% CI -5.95 to 10.66), p=0.57).

HARMS: 43 adverse events (AEs), most commonly cough and chest pain/discomfort, occurred in 19 subjects (49%) of the HBOT group and 38 AEs in 18 subjects (44%) of the placebo group, one serious AE in HBOT and one death in the placebo group.

CONCLUSIONS: 10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved, with a notable sex difference. HBOT has a favourable harm profile.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04842448), EudraCT (2021-000764-30). The trial was funded by Vetenskapsrådet (2022-00834), Region Stockholm (2020-0731, 2022-0674), Hjärt-Lungfonden and OuraHealth Oy.}, } @article {pmid40227084, year = {2025}, author = {Ottaway, Z and Campbell, L and Fox, J and Burns, FM and Hamzah, L and Schoeman, S and Price, D and Clarke, A and Pett, SL and Onyango, D and Sabin, C and Miller, RF and Post, FA and , }, title = {Post-acute sequelae of COVID-19 in people of Black ethnicities living with HIV in the United Kingdom.}, journal = {International journal of STD & AIDS}, volume = {}, number = {}, pages = {9564624251334227}, doi = {10.1177/09564624251334227}, pmid = {40227084}, issn = {1758-1052}, abstract = {BackgroundThe COVID-19 pandemic disproportionately affected people of Black ethnicities, however, there are limited data on the post-acute sequelae of COVID-19 infection in these populations, and none in those with HIV.MethodsWe conducted a cross-sectional study in people of Black ethnicities with HIV in the UK. Participants were assessed for functional impairment, frailty, respiratory symptoms, anxiety and depression; they were also asked to rate aspects of their physical and mental health on a scale from 1 (poor) to 10 (excellent), both at enrolment and prior to the pandemic. We report associations with COVID-19 history and recovery status.ResultsWe enrolled 183 participants between June 2021 and October 2022, 131 (72%) of whom reported COVID-19. A history of COVID-19 was associated with a reduced ability to carry out usual activities (OR 2.54 [1.03-6.21], p = 0.04), an increase in pain, tiredness and breathlessness, and overall decline in physical health. Of those with a history of COVID-19, 111 (85%) reported to have fully recovered. Those who had not fully recovered reported poorer functional status (p < 0.001) and had higher generalised anxiety scores (p = 0.02). Objective measures of physical function were similar in those who reported no COVID-19, COVID-19 with full recovery, and COVID-19 with incomplete recovery.ConclusionsIn this cohort of Black people with HIV, participants with a history of COVID-19 reported a reduced ability to carry out activities of daily living and various other health issues. Although most people reported full recovery from COVID-19, self-reported limitations in functional status and anxiety were common sequelae.}, } @article {pmid40226780, year = {2025}, author = {Zhang, H and Yang, P and Gu, X and Sun, Y and Zhang, R and Zhang, D and Zhang, J and Wang, Y and Ma, C and Liu, M and Ma, J and Li, A and Wang, Y and Ma, X and Cui, X and Wang, Y and Liu, Z and Wang, W and Zheng, Z and Li, Y and Wu, J and Wang, Q and Cao, B}, title = {Health outcomes one year after Omicron infection among 12,789 adults: a community-based cross-sectional study.}, journal = {The Lancet regional health. Western Pacific}, volume = {56}, number = {}, pages = {101507}, pmid = {40226780}, issn = {2666-6065}, abstract = {BACKGROUND: Characterizing the paradigm and impact of long COVID is crucial for addressing this worldwide health challenge. This study aimed to investigate the prevalence of long COVID one year after primary Omicron infection and characterize differences in long-term health consequence between participants with persistent long COVID and those who fully recovered.

METHODS: This a community-based cross-sectional study conducted from December 2023 to March 2024 at the China-Japan Friendship Hospital and 16 administrative districts in Beijing. 12,789 participants infected with Omicron between December 2022 and January 2023 were recruited through stratified multistage random sampling and included in the final analysis. Of them, 376 participants with persistent long COVID and 229 without long COVID were matched for further physical examinations. The primary outcome was the prevalence of long COVID one year after infection. Secondary outcomes included muscle strength, exercise capacity, health-related quality of life (HRQoL), mental health, work status, laboratory tests, and examinations.

FINDINGS: Among 12,789 participants (media [IQR] age, 48.4 [37.3 to 61.4] years; 7817 females [61.1%]), 995 of them (7.8%) experienced long COVID within one year, with 651 (5.1%) having persistent symptoms. Fatigue (598/995 [60.1%]) and post-exertional malaise (367/995 [36.9%]) were the most common symptoms. Brain fog had the lowest resolution proportion as 4.2% within one year. The odds of long COVID increased with reinfections (odds ratios for one reinfection 2.592 [95% CI: 2.188 to 3.061]; two or more: 6.171 [3.227 to 11.557]; all p < 0.001). Participants with persistent long COVID had markedly lower muscle strength (upper-limb: 26.9 ± 12.4 vs. 29.1 ± 14.5 Kg; lower-limb: 40.0 [27.0 to 62.0] vs. 43.0 [28.0 to 59.0] s), worse exercise capacity and poorer HRQoL, and meaningful difference in laboratory tests results compared to those without long COVID. They also exhibited significantly higher proportions of abnormal lung function (FEV1 %pred<80%: 13.0% vs. 2.0%; DLco %pred<80%: 32.7% vs. 19.9%) and lung imaging abnormalities (23.5% vs. 13.6%).

INTERPRETATION: The considerable health burden of long COVID and the progression of neurological symptoms following Omicron infection warrant close monitoring. Utilizing professional questionnaires and developing reliable diagnostic tools are necessary for improving diagnosis and treatment of long COVID.

FUNDING: This work was supported by Beijing Research Center for Respiratory Infectious Diseases (BJRID2024-012), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2022-I2M-CoV19-005/CIFMS 2021-I2M-1-048), the National Natural Science Foundation of China (82241056/82200114/82200009), the New Cornerstone Science Foundation.}, } @article {pmid40226209, year = {2025}, author = {de Assumpção, LECC and Romeo, BGP and Guerra, JCC and Camargo, LFA and Nagaoka, MA and Amgarten, DE and Dorlass, EG and Petroni, RC and Cardoso, ACA and Ruiz, RM and Bittante, CD and Teich, VD and Pinho, JRR and Doi, AM}, title = {Case report: Persistent COVID-19 in a patient with B cell lymphoma refractory to antiviral treatment due to resistance to Remdesivir.}, journal = {IDCases}, volume = {40}, number = {}, pages = {e02199}, pmid = {40226209}, issn = {2214-2509}, abstract = {BACKGROUND: There is a significant concern of the pandemic impact of SARS-CoV-2 infection in immunocompromised patients. These patients can develop long COVID-19 due to impairment of cellular and humoral immunity. On the other hand, prolonged infection can lead to mutations in the SARS CoV-2 genome that can impact on the resistance to antiviral therapy. Remdesivir cases have been reported in patients receiving antiviral drug treatment.

CASE PRESENTATION: A 46-year-old male with previous mantle cell lymphoma resolved by autologous bone marrow transplantation without other comorbidities had SARS-CoV-2 detected in February 2022 and received the recommended antiviral treatment with Remdesivir. COVID-19 evolved in four months with worsening of the symptoms, despite an initial rapid improvements and high RT-PCR Ct values. The patient was relieved from hospital care stable and well but still maintaining positive test results.

CONCLUSIONS: the patient presented prolonged COVID-19 with persistence of virus detected by RT-PCR for several months. The strain sequenced presented a mutation different from all reported previously. Although it was no possible to sequence the initial strain without these mutations, our data suggests that immunocompromised patient with prolonged COVID-19 may serve as reservoir for strains of SARS-CoV-2 with resistant components in his genome.}, } @article {pmid40224556, year = {2025}, author = {Carpio-Orantes, LD}, title = {From long COVID to neurodegeneration.}, journal = {Brain circulation}, volume = {11}, number = {1}, pages = {94-95}, pmid = {40224556}, issn = {2455-4626}, } @article {pmid40223754, year = {2025}, author = {Chuang, CH and Wang, YH and Yeh, LT and Yeh, CB}, title = {Long-Term Stroke and Mortality Risk Reduction Associated With Acute-Phase Paxlovid Use in Mild-to-Moderate COVID-19.}, journal = {Journal of medical virology}, volume = {97}, number = {4}, pages = {e70351}, doi = {10.1002/jmv.70351}, pmid = {40223754}, issn = {1096-9071}, support = {//This study was supported by Chung Shan Medical University Hospital./ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; Retrospective Studies ; *COVID-19/mortality/complications ; *COVID-19 Drug Treatment ; Adult ; *Stroke/prevention & control/mortality ; Aged, 80 and over ; SARS-CoV-2 ; Risk Factors ; *Antiviral Agents/therapeutic use ; United States/epidemiology ; }, abstract = {This retrospective cohort study investigated whether Paxlovid (nirmatrelvir/ritonavir) use during the acute phase of mild-to-moderate COVID-19 reduces the risk of ischemic or hemorrhagic stroke occurring more than 3 months post-diagnosis, a condition classified as long COVID. Utilizing TriNetX electronic health records comprising 118 million patients in the United States, adults aged 18 years or older with confirmed COVID-19 diagnoses from 2022 to 2023 were categorized into Paxlovid (administered within 5 days of diagnosis) and non-Paxlovid groups. Exclusion criteria included prior cerebrovascular disease, mortality within 3 months, use of specific antivirals, and severe clinical conditions such as ICU admission, intubation, mechanical support, SpO2 < 90%, respiratory rate > 30/min, sepsis, systemic inflammatory response syndrome, and acute respiratory distress syndrome. The index date was the initial COVID-19 diagnosis. Propensity score matching in a 1:1 ratio controlled for confounding factors, and stroke (ischemic or hemorrhagic) and mortality were analyzed using Kaplan-Meier survival curves and Cox proportional hazards models. Among 181 992 matched pairs, Paxlovid use was associated with a significantly reduced risk of ischemic and hemorrhagic stroke (hazard ratio [HR] 0.85; 95% confidence interval [CI]: 0.80-0.89) and all-cause mortality (HR 0.68; 95% CI: 0.63-0.73) during the long COVID period, defined as more than 90 days post-diagnosis. Subgroup analyses demonstrated consistent protective effects across age, sex, BMI, comorbidities such as hypertension, diabetes, and hyperlipidemia, and vaccination status. Notably, older adults (HR 0.81; 95% CI: 0.76-0.86) and individuals with metabolic conditions, including obesity (HR 0.86; 95% CI: 0.78-0.96), exhibited pronounced benefits, and the protective effects were observed irrespective of vaccination status. These findings highlight that Paxlovid use during the acute phase of COVID-19 significantly reduces the risk of long-term cerebrovascular events and mortality, emphasizing its critical role in mitigating long-term complications associated with COVID-19.}, } @article {pmid40223130, year = {2025}, author = {Coste, J and Delpierre, C and Robineau, O and Rushyizekera, M and Richard, JB and Alleaume, C and Gallay, A and Tebeka, S and Steichen, O and Lemogne, C and Makovski, TT}, title = {A multidimensional network of factors associated with long COVID in the French population.}, journal = {Communications medicine}, volume = {5}, number = {1}, pages = {114}, pmid = {40223130}, issn = {2730-664X}, abstract = {BACKGROUND: Various factors associated with long COVID have been evidenced, but the heterogeneity of definitions and epidemiological investigations has often hidden risk pathways relevant for understanding and preventing this condition.

METHODS: This nationwide random sampling survey conducted in France after the Omicron waves in autumn 2022 assessed eight sets of factors potentially associated with long COVID in a structured epidemiological investigation based on a conceptual model accounting for the relationships between these sets of factors. A representative sample of 1813 adults of whom 55% were infected with SARS-CoV-2 was assessed for infection dates and context, post-COVID symptoms and these factors. Four definitions of long COVID, including the World Health Organisation's, were used.

RESULTS: Female sex, household size (≥2), low financial security, negative impact of COVID-19 pandemic on occupation and work conditions, number of comorbidities (≥2), presence of respiratory disease, mental and sensory disorders, number of SARS-CoV-2 infections (≥2) and initial symptoms (≥6), perceived high severity of COVID-19 are positively and consistently associated with long COVID. Age ≥ 75 years, retirement, SARS-CoV-2 vaccination (≥2 doses) and good perceived information regarding long Covid are negatively associated with the condition.

CONCLUSIONS: The broad spectrum of factors confirmed here strongly suggests that long COVID should be regarded not only as a direct complication of SARS-CoV-2 infection but also as driven by a broader network of contextual, medical, psychological and social factors. These factors should be better considered in strategies aimed at limiting the long COVID burden in the general population.}, } @article {pmid40222950, year = {2025}, author = {Angelhoff, C and Jedenfalk, M and Fernlund, E and Svensson, E and Duchen, K and Ertzgaard, P}, title = {Development and Validation of POCOKIDS-Q-A Questionnaire to Assess Post COVID-19 Symptoms in Children.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.70094}, pmid = {40222950}, issn = {1651-2227}, support = {//The Joanna Cocozza Foundation for Children's Medical Research/ ; FORSS-994671//Forskningsrådet i Sydöstra Sverige/ ; //Majblommans Riksförbund/ ; //Henry and Ella Margareta Ståhls Stiftelse/ ; }, abstract = {AIM: To identify the symptom burden in children and adolescents with post COVID-19, a validated and reliable instrument is needed, particularly to assess symptoms and their impact on the child. The aim of this study was to describe the development, validation, and reliability of the Post COVID-19 in Kids Questionnaire (POCOKIDS-Q), which was designed to assess post COVID-19 symptoms in children and adolescents.

METHODS: The POCOKIDS-Q was developed based on literature, clinical experience, and questionnaires for adults with post COVID-19. The linguistic validation involved 9- to 17-year-old children. Children and adolescents with the onset of post COVID-19 symptoms were asked to complete the final version through a web link. Exploratory and confirmatory factor analyses were performed to identify a factor structure that explains the covariances between the variables.

RESULTS: The link to the POCOKIDS-Q was opened 324 times and fully completed by 213 (66%) children and young adults (median age 14 years) with post COVID-19 symptoms. Confirmatory factor analyses revealed four significant and correlated factors: brain fatigue, cognitive impact, physical impact, and emotional impact. The explanatory power of the factor model is high.

CONCLUSION: The POCOKIDS-Q is applicable for assessing post COVID-19 symptoms in children and young adults.}, } @article {pmid40221847, year = {2025}, author = {Sarma, N and Gage, S and Hough, CL and Hope, AA}, title = {'We Don't Have to Prove to People How We're Feeling': Understanding the Role of Peer Support Groups in Countering Epistemic Injustices in Long COVID at a US Centre.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70266}, pmid = {40221847}, issn = {1369-7625}, support = {//Dr. Hope is supported by grants from the NIH/NHLBI (K01 HL140279)./ ; }, mesh = {Humans ; *COVID-19/psychology ; Female ; Male ; *Peer Group ; Middle Aged ; Qualitative Research ; *Self-Help Groups ; Adult ; Interviews as Topic ; SARS-CoV-2 ; Aged ; Chronic Disease/psychology ; *Social Justice/psychology ; }, abstract = {BACKGROUND: Long COVID, an infection-associated chronic condition characterised by new or worsening signs or symptoms for more than 3 months after a SARS-CoV-2 infection, is a chronic debilitating illness which remains poorly understood. Epistemic injustice in healthcare describes the unique harms or wrongs done to a person in their capacity to share and acquire knowledge about their illness. Although the concept of epistemic injustice has been described in other chronic conditions, few studies have explored these concepts in Long COVID.

OBJECTIVES: (1) To understand the lived experience of epistemic injustice in adults with Long COVID who were participating in a peer support group intervention and (2) to describe the potential impact of the support group on these experiences in participants.

METHODS: Qualitative analysis utilising inductive analysis of semi-structured individual interviews of patients with Long COVID who participated in a peer support group intervention at an academic medical centre in Oregon, USA.

RESULTS: We identified three themes that captured the lived experiences of epistemic injustice in Long COVID support group participants: (1) dismissal and disregard; (2) episodic and unpredictable symptoms and impairment, and (3) knowledge and interpretation practices. We also found that the peer support potentially impacted these experiences of epistemic injustice through (1) recognition and validation; (2) solidarity and community, and (3) information exchange and expectation setting.

CONCLUSIONS: Long COVID patients are at risk of experiencing epistemic injustice in seeking healthcare for this complex condition. Peer support programmes may be one approach to help counter these experiences and should be further studied as a complex intervention for improving patient-centred care in Long COVID.}, } @article {pmid40221694, year = {2025}, author = {Chepo, M and Martin, S and Déom, N and Khalid, AF and Vindrola-Padros, C}, title = {Mind the gap: examining policy and social media discourse on Long COVID in children and young people in the UK.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {1373}, pmid = {40221694}, issn = {1471-2458}, support = {MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; MR/W029766/1//MRC-UKRI Better Methods, Better Research/ ; }, mesh = {Humans ; *Social Media ; *COVID-19/epidemiology ; United Kingdom/epidemiology ; Child ; *Health Policy ; Adolescent ; *Policy Making ; }, abstract = {BACKGROUND: Long COVID in children and young people (CYP) has posed significant challenges for health systems worldwide. Despite its impact on well-being and development, policies addressing the needs of CYP remain underdeveloped. This study examines UK Long COVID policies using ethical frameworks, integrating policy and social media analyses to explore public and professional concerns.

METHODS: A mixed-methods approach was applied. Policy documents were reviewed using Thompson et al.'s pandemic preparedness framework and Campbell and Carnevale's child-inclusive ethical model. Social media discourse (12,650 posts) was analysed using Brandwatch™ to identify key themes around CYP and Long COVID policies. Data was collected and triangulated through the LISTEN method, which integrates policy analysis with social media discourse to ensure a holistic understanding of systemic gaps and public perceptions.

RESULTS: Analysis highlighted gaps in accountability, inclusiveness, and transparency in policy development. Social media data reflected significant public dissatisfaction, primarily critiquing government accountability (90% of posts) and delayed policy responsiveness (29% of posts). Key ethical challenges included limited CYP representation and unequal access to services.

CONCLUSIONS: Recommendations include improving transparency, incorporating CYP perspectives in policymaking, and ensuring equitable access to care. These findings provide a foundation for ethically sound and inclusive policies addressing Long COVID in CYP.}, } @article {pmid40219044, year = {2025}, author = {Marchesi, N and Allegri, M and Bruno, GM and Pascale, A and Govoni, S}, title = {Exploring the Potential of Dietary Supplements to Alleviate Pain Due to Long COVID.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40219044}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements ; *COVID-19/complications ; SARS-CoV-2 ; *Chronic Pain/etiology ; Analgesics/therapeutic use ; *Pain Management/methods ; Post-Acute COVID-19 Syndrome ; *Pain/etiology/drug therapy ; }, abstract = {Long COVID, characterized by persistent symptoms following COVID-19 infection, significantly impacts individuals' health and daily functioning due to fatigue and pain. Focusing on pain, this review addresses nociplastic and chronic pain conditions. Interventions designed to reduce inflammation, oxidative stress, and enhance vagal activity may offer a promising approach to managing post-pandemic pain. This review presents individual components of food supplements with demonstrated efficacy in one or more pain conditions, focusing on their proposed mechanisms and clinical activity in pain, including their use in post-COVID-19 pain when available. Many of these substances have a long history of safe use and may offer an alternative to long-term analgesic drug treatment, which is often associated with potential side effects. This review also explores the potential for synergistic effects when combining these substances with each other or with conventional analgesics, considering the advantages for both patients and the healthcare system in using these substances as adjunctive or primary therapies for pain symptoms related to long COVID. While preclinical scientific literature provides a mechanistic basis for the action of several food supplements on pain control mechanisms and signaling pathways, clinical experience, particularly in the field of long COVID-associated pain, is still limited. However, the reviewed literature strongly suggests that the use of food supplements in long COVID-associated pain is an attainable goal, provided that rigorous clinical trials are conducted.}, } @article {pmid40218944, year = {2025}, author = {Umsumarng, S and Semmarath, W and Arjsri, P and Srisawad, K and Intanil, I and Jamjod, S and Prom-U-Thai, C and Dejkriengkraikul, P}, title = {Anthocyanin-Rich Fraction from Kum Akha Black Rice Attenuates NLRP3 Inflammasome-Driven Lung Inflammation In Vitro and In Vivo.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40218944}, issn = {2072-6643}, support = {FF059/2567//Fundamental Fund 2024, Chiang Mai University, Thailand/ ; }, mesh = {*Anthocyanins/pharmacology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Animals ; Humans ; *Inflammasomes/metabolism/drug effects ; Mice, Inbred C57BL ; *Oryza/chemistry ; A549 Cells ; *Plant Extracts/pharmacology ; Mice ; *Pneumonia/drug therapy/metabolism ; *Anti-Inflammatory Agents/pharmacology ; Disease Models, Animal ; Male ; Lipopolysaccharides ; Lung/drug effects/pathology ; }, abstract = {BACKGROUND/OBJECTIVES: Chronic lower respiratory tract inflammation can result from exposure to bacterial particles, leading to the activation of the NLRP3 inflammasome pathway. These effects may cause irreversible respiratory damage, contributing to persistent lung injury and chronic obstructive pulmonary disease (COPD), as observed in long COVID or bacterial pneumonia in older adults' patients. Given its profound impact, the NLRP3 inflammasome has emerged as a key therapeutic target for mitigating aberrant inflammatory responses.

METHODS: In this study, we investigated the anti-inflammatory effects of Kum Akha black rice, a functional food, on the attenuation of NLRP3 inflammasome pathway using lipopolysaccharide-induced A549 lung epithelial cells and a C57BL/6NJcl mouse model. The anthocyanin-rich fraction from Kum Akha black rice germ and bran extract (KA1-P1) was obtained using a solvent-partitioned extraction technique.

RESULTS: KA1-P1 exhibited a high anthocyanin content (74.63 ± 1.66 mg/g extract) as determined by the pH differential method. The HPLC analysis revealed cyanidin-3-O-glucoside (C3G: 45.58 ± 0.48 mg/g extract) and peonidin-3-O-glucoside (P3G: 6.92 ± 0.29 mg/g extract) as its anthocyanin's active compounds. Additionally, KA1-P1 demonstrated strong antioxidant activity, as assessed by DPPH and ABTS assays. KA1-P1 (12.5-100 μg/mL) possessed inhibitory effects on LPS + ATP-induced A549 lung cells inflammation through the significant suppressions of NLRP3, IL-6, IL-1β, and IL-18 mRNA levels and the inhibition of cytokine secretions in a dose-dependent manner (p < 0.05). Mechanistic analysis revealed that KA1-P1 downregulated key proteins in the NLRP3 inflammasome pathway (NLRP3, ASC, pro-caspase-1, and cleaved-caspase-1). Furthermore, in vivo studies demonstrated that KA1-P1 significantly diminished LPS-induced lower respiratory inflammation in C57BL/6NJcl mice, as evidenced by the reduced bronchoalveolar lavage fluid and blood levels of inflammatory cytokines (IL-6, IL-1β, and IL-18) and diminished histopathological inflammatory lung lesions.

CONCLUSIONS: Overall, our findings suggest that the anti-inflammatory properties of KA1-P1 may support its application as a functional supplement or promote the consumption of pigmented rice among the elderly to mitigate chronic lower respiratory tract inflammation mediated by the NLRP3 inflammasome pathway.}, } @article {pmid40218919, year = {2025}, author = {Ayats-Vidal, R and Albiciuc, IA and Bruch-Molist, C and Cuartero-Gorjón, A and Cordobilla, B and Pedrosa-Domínguez, M and Susanna-Calero, M and García-González, M and Valdesoiro-Navarrete, L and Larramona-Carrera, H and Asensio-de la Cruz, O and Castro-Marrero, J and Domingo, JC}, title = {Erythrocyte Fatty Acid Profile, Mediterranean Diet and Asthma Severity in Childhood Allergic Asthma: Preliminary Findings from a Cohort Study in Spain.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40218919}, issn = {2072-6643}, support = {2022 SEICAP//Spanish Society of Clinical Immunology, Allergology and Pediatric Asthma/ ; }, mesh = {Humans ; *Asthma/blood/epidemiology ; *Diet, Mediterranean ; Male ; Female ; Child ; Spain/epidemiology ; *Erythrocytes/chemistry/metabolism ; Cross-Sectional Studies ; Prospective Studies ; Severity of Illness Index ; Fatty Acids, Omega-3/blood ; *Fatty Acids/blood ; Adolescent ; Cohort Studies ; Child, Preschool ; }, abstract = {Background: Allergic asthma incidence is increasing, probably due to the influence of the Western diet. Adherence to the Mediterranean diet (MedDi) and omega-3 fatty acids composition (n-3 PUFAs) may be linked to a lower prevalence and lower severity of childhood asthma; however, the association is inconclusive. This study aims to examine the relationship between adherence to the MedDi, asthma severity, and erythrocyte fatty acid profile in Spanish children with atopic asthma. Methods: This study was based on an ongoing single-center, prospective, cross-sectional cohort study involving 95 consecutively enrolled children from an outpatient tertiary referral center. Of these, 55 had atopic asthma and 40 were age-matched healthy controls. Blood samples were collected to analyze the erythrocyte fatty acid content. Participants' demographic and clinical characteristics were recorded using validated self-reported outcome measures. Asthma severity and pulmonary function were assessed. Results: Asthmatics presented poorer adherence to the MedDi (p = 0.034) and lower n-3 PUFA levels (p = 0.019). Asthmatics with poor adherence to the MedDi were more likely to be overweight (p = 0.001) and to have moderate-severe asthma (p = 0.049); and lower n-3 PUFAs levels (p = 0.033). Children with mild asthma had higher n-3 PUFAs levels than those with moderate or severe asthma (p = 0.036). Conclusions: These findings highlight that adherence to the MedDi and a high erythrocyte fatty acid profile seem to have a protective effect in childhood asthma. Future well-controlled interventions should focus on the effects of MedDi patterns and n-3 PUFA intake on the primary prevention of childhood asthma.}, } @article {pmid40218114, year = {2025}, author = {Gölz, LA and Poß-Doering, R and Merle, U and Wensing, M and Stengel, S}, title = {Patient Perspectives on the Care in a Long COVID Outpatient Clinic-A Regional Qualitative Analysis from Germany.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, doi = {10.3390/healthcare13070818}, pmid = {40218114}, issn = {2227-9032}, support = {no grant number//Ministry of Science, Research and Arts of the State of Baden-Wuerttemberg; Germany/ ; }, abstract = {Background/Objectives: Long COVID specialized outpatient clinics (sOCs), which are part of the recommended long COVID care, usually face high demand. Few studies focused on the experience of care in such facilities in Germany. This study investigated how patients experience care in a sOC at a German university hospital. Methods: Semi-structured interviews were conducted with patients attending this clinic between October 2022 and January 2023. Data analysis was based on thematic analysis. Results: The themes from interviews with 14 patients (F = 11, M = 3) could be broadly categorized into statements on the pathway to the sOC, and statements on care provided in the sOC. Findings show that patients' high expectations at the sOC appointment were shaped by previous experiences with care, which were mainly perceived as inadequate. Care in the sOC was predominantly perceived as competent, empathetic and relevant for further care and coping with the disease. A deterioration in health directly related to the consultation (classifiable as post-exertional malaise) was frequently described, as was a high need for ongoing consultation. Conclusions: Overall, the findings point to a need for adaptations in the sOC, such as identifying optimized models of care and tailoring them to the patients' limited resources. This includes measures to improve care outside the sOC.}, } @article {pmid40217997, year = {2025}, author = {Bassem, A and Hussein, A and Sharawe Taha, MA and El Sayed, SM and Sadek, EM and AlRasheed, HA and Bahaa, MM and Kamal, M}, title = {Persistent Symptoms and Associated Risk Factors of COVID-19: A Cross-Sectional Study in Minia, Upper Egypt.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, doi = {10.3390/healthcare13070699}, pmid = {40217997}, issn = {2227-9032}, abstract = {Background: A significant number of COVID-19 survivors around the world have been reporting persistent symptoms following their recovery. Long COVID is recognized as a condition affecting not only the respiratory but also the gastrointestinal, cardiovascular, neurological, immune, and hematopoietic systems. Objective: This study aimed to describe persistent symptoms in COVID-19 survivors six months post-infection in Minia, Upper Egypt, and investigate associated risk factors. Methods: This observational cross-sectional study included 189 hospitalized and non-hospitalized patients previously diagnosed with COVID-19. Demographic data, symptom severity, comorbidities, and persistent symptoms were collected. A logistic regression analysis was used to identify risk factors associated with long COVID, with statistical significance set at p < 0.05. Results: In total, 68.8% of participants were women, and 83.5% of patients reported at least one ongoing symptom. The most self-reported symptoms were fatigue (73.5%) and myalgia (45.5%), followed by dyspnea (43.3%). Age was associated with an increased risk of developing long COVID (OR 1.028, 95% CI 1.003-1.054, p = 0.030). Patients who were hospitalized during the acute phase had more than twice the risks of having persistent symptoms (OR 2.384, 95% CI 1.055-5.387, p = 0.037). Conclusions: A substantial proportion of COVID-19 survivors in Minia, Upper Egypt, continues to experience persistent symptoms, primarily constitutional and neurological manifestations. Many patients reported self-medicating with unprescribed antibiotics, highlighting a need for public awareness regarding viral infections and the risks associated with improper antibiotic use.}, } @article {pmid40217157, year = {2025}, author = {Seixas, AFAM and Marcolino, MS and Guimarães, FS and Rocha, GM and Menezes, AC and Silva, HKC and Cardoso, CS}, title = {Exploring the landscape of long COVID: prevalence and associated factors in patients assisted by a telehealth service.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {509}, pmid = {40217157}, issn = {1471-2334}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; Adult ; Cross-Sectional Studies ; *Telemedicine ; Prevalence ; SARS-CoV-2 ; Aged ; Comorbidity ; Risk Factors ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID is a condition that occurs in patients with a previous history of COVID-19, and symptoms that cannot be explained by another diagnosis persist.

OBJECTIVE: To evaluate the prevalence of long COVID and associated factors in patients treated with a public telehealth service during acute COVID-19.

METHOD: This was a cross-sectional study involving users of a COVID-19 telehealth service offered during the critical phase of the pandemic, called TeleCOVID-MG. Individuals older than 18 years of age who tested positive for SARS-CoV-2 and were monitored during social isolation were eligible. Prevalence was calculated, and descriptive analysis and group comparisons (patients with and without long COVID symptoms) were performed in addition to logistic regression with odds ratios and 95% confidence intervals.

RESULTS: Among the 699 patients included in the study, 60.8% were women aged between 30 and 49 years (44.6%) and had a high school education (46.5%). The main comorbidities were hypertension (20.9%), diabetes (8.3%), and heart disease (3.9%). The incidence of long COVID was 26.8% (95% CI: 23.5; 30.1). Cognitive symptoms (49.7%), chronic diarrhea (49.2%), and cough (40.6%) were the most persistent symptoms. Female sex (OR: 2.51), secondary education (OR: 2.13), elementary education (OR: 2.81), monthly income between 600 and 1,000 USD (OR: 5.85), supplementary health assistance (OR: 1.98), anosmia during acute COVID-19 (OR: 4.52) and need for in-person care (OR: 2.44) were factors associated with a higher incidence of long COVID.

CONCLUSION: Long COVID affected almost one-third of the study population. Although the COVID-19 pandemic is under control, the virus continues to infect individuals, raising doubts about the long-term complications of the disease.}, } @article {pmid40215369, year = {2025}, author = {Greaves, K and King, A and Bourne, Z and Welsh, J and Morgan, M and Tolosa, MX and Johnston, T and Bonner, C and Stanton, T and Korda, R}, title = {Consent to recontact for future research using linked primary healthcare data: Outcomes and general practice perceptions from the ATHENA COVID-19 study.}, journal = {Clinical trials (London, England)}, volume = {22}, number = {2}, pages = {188-199}, doi = {10.1177/17407745241304094}, pmid = {40215369}, issn = {1740-7753}, mesh = {Humans ; *COVID-19/epidemiology ; *Primary Health Care ; *Informed Consent ; Male ; Queensland/epidemiology ; Female ; Middle Aged ; *General Practice ; Adult ; Aged ; *Patient Selection ; SARS-CoV-2 ; Clinical Trials as Topic ; }, abstract = {BACKGROUND: The ATHENA COVID-19 study was set up to recruit a cohort of patients with linked health information willing to be recontacted in future to participate in clinical trials and also to investigate the outcomes of people with COVID-19 in Queensland, Australia, using consent. This report describes how patients were recruited, their primary care data extracted, proportions consenting, outcomes of using the recontact method to recruit to a study, and experiences interacting with general practices requested to release the primary care data.

METHODS: Patients diagnosed with COVID-19 from 1 January 2020 to 31 December 2020 were systematically approached to gain consent to have their primary healthcare data extracted from their general practice into a Queensland Health database and linked to other datasets for ethically approved research. Patients were also asked to consent to allow future recontact to discuss participation in clinical trials and other research studies. Patients who consented to recontact were later approached to recruit to a long-COVID study. Patients' general practices were contacted to export the patient files. All patient and general practice interactions were recorded. Outcome measures were proportions of patients consenting to data extraction and research, permission to recontact, proportions of general practices agreeing to participate. A thematic analysis was conducted to assess attitudes regarding export of healthcare data, and the proportions consenting to participate in the long-COVID study were also reported.

RESULTS: Of 1212 patients with COVID-19, contact details were available for 1155; 995 (86%) were successfully approached, and 842 (85%) reached a consent decision. Of those who reached a decision, 581 (69%), 615 (73%) and 629 (75%) patients consented to data extraction, recontact, and both, respectively. In all, 382 general practices were contacted, of whom 347 (91%) had an electronic medical record compatible for file export. Of these, 335 (88%) practices agreed to participate, and 12 (3%) declined. In total, 526 patient files were exported. The majority of general practices supported the study and accepted electronic patient consent as legitimate. For the long-COVID study, 376 (90%) of those patients recontacted agreed to have their contact details passed onto the long-COVID study team and 192 (53%) consented to take part in their study.

CONCLUSION: This report describes how primary care data were successfully extracted using consent, and that the majority of patients approached gave permission for their healthcare information to be used for research and be recontacted. The consent-to-recontact concept demonstrated its effectiveness to recruit to new research studies. The majority of general practices were willing to export identifiable patient healthcare data for linkage provided consent had been obtained.}, } @article {pmid40215290, year = {2025}, author = {Medeiros, RS and Neves, L and Sousa, I and Pereira, BD}, title = {Arginine-vasopressin deficiency due to long COVID-associated infundibulo-neurohypophysitis.}, journal = {Archives of endocrinology and metabolism}, volume = {68}, number = {}, pages = {e240168}, doi = {10.20945/2359-4292-2024-0168}, pmid = {40215290}, issn = {2359-4292}, mesh = {Humans ; *COVID-19/complications ; Male ; Middle Aged ; *Diabetes Insipidus, Neurogenic/etiology/diagnosis ; *Arginine Vasopressin/deficiency ; SARS-CoV-2 ; }, abstract = {Long COVID is defined by the occurrence of signs, symptoms, and conditions that develop after COVID-19 and may affect several organs and systems. Arginine-vasopressin deficiency (AVP-D; central diabetes insipidus) is a very rare complication of COVID-19 and SARS-CoV-2 immunization. Case reports, original studies, and reviews on AVP-D and long COVID published until February 2024 were retrieved from PubMed. A 47-year-old man presented with polydipsia, polyuria, memory loss, and mental fog 8 weeks after an episode of mild COVID-19. His past personal and family medical history were unremarkable. Biochemical evaluation was relevant for low urine osmolality and a 24-hour urine volume of 10,350 mL. Basal anterior pituitary evaluation was normal. A water deprivation test was started and interrupted after 2 hours due to the development of hypernatremia, high serum osmolality, and low urine osmolality. Urine osmolality significantly increased after intranasal desmopressin 20 μg. Contrast-enhanced pituitary MRI was suggestive of infundibulo-neurohypophysitis. Further biochemical, genetic, and imaging tests excluded secondary AVP-D causes.The patient was subsequently started on oral desmopressin, showing prompt response. After a follow-up of 20 months, he remained well-controlled with isolated AVP-D. Although molecular and histologic confirmation of SARS-CoV-2 infundibulo-neurohypophysitis could not be investigated, a strong temporal relationship and the absence of an alternative diagnosis rendered plausible the inclusion of AVP-D in the myriad of long COVID manifestations. Further studies with patients recovered from COVID-19 are necessary for a better understanding of the epidemiology, pathophysiology, and clinical course of this very rare endocrine condition.}, } @article {pmid40215236, year = {2025}, author = {J, VK and Koshy, JM and S, D and Narreddy, S and Gowri S, M and Rupali, P and Sathyendra, S}, title = {Prevalence and predictors of long COVID at 1 year in a cohort of hospitalized patients: A multicentric qualitative and quantitative study.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320643}, pmid = {40215236}, issn = {1932-6203}, mesh = {Humans ; Male ; *COVID-19/epidemiology/complications ; Female ; Middle Aged ; Prevalence ; Adult ; Quality of Life ; Hospitalization ; SARS-CoV-2/isolation & purification ; India/epidemiology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Aged ; }, abstract = {INTRODUCTION: According to WHO long COVID is defined as a continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. We followed up patients after an episode of acute COVID-19 for 1 year after hospital discharge from different parts of India.

METHODS: This was a multi-centric study among patients ≥18 years hospitalized with COVID-19, which recruited patients at 6 weeks after hospital discharge (baseline). Quantitative data on demographics, pre-existing co-morbidities, risk factors, signs and symptoms and hospital parameters during acute COVID-19 infection were noted at baseline. They were followed up and data collected telephonically thereafter at 3-6, 6-9 and 9-12 months regarding self-reported persistence of symptoms. A qualitative component included face to face in-depth interviews to elicit information on perceived health problems, quality of life and financial burden due to COVID-19.

RESULTS: A total of 315 patients were enrolled, with the majority being males (59.4%). The median age was 52 years (IQR 40, 63). The prevalence of long COVID was 16.5%. At 6 weeks and 12 months, 35.2% and 25.9% of patients, reported more than one new symptom that affected their quality of life. Shortness of breath was common at each time point, persistent muscle pain and weakness waxed and waned. Variables at 6 weeks post discharge (baseline) such as shortness of breath (OR 2.22 CI 1.06-4.65, p = <0.05), cough (OR 6.93, CI 2.36-20.30, p = <0.05), fatigue (OR 2.34, CI 1.05-5.23, p = <0.05), and weight loss (OR 2.90, CI 1.30-6.49, p = <0.05) were significantly associated with long COVID.

CONCLUSION: We found that long COVID was noted in 16.5% patients who self reported non - recovery at 1 year. Physical symptoms, mental health issues and mobility were persistent in a significant number of patients following an initial recovery from an acute COVID-19 infection. In 25.9% of patients more than 1 symptom was reported at 1 year after COVID-19. We urgently need therapeutic interventions which can improve the quality of life in these patients.}, } @article {pmid40212283, year = {2025}, author = {Brodwall, EM and Selvakumar, J and Havdal, LB and Sommen, S and Berven, LL and Cvejic, E and Bratholm Wyller, VB and Pedersen, M}, title = {Predictors of fatigue progression in long COVID among young people.}, journal = {Brain, behavior, & immunity - health}, volume = {45}, number = {}, pages = {100982}, pmid = {40212283}, issn = {2666-3546}, abstract = {Long COVID, or post-COVID-19 condition (PCC), has emerged as a significant health concern, with fatigue being the most prevalent persistent symptom among young people. However, research on predictors of fatigue progression in young populations is limited. This study aimed to investigate factors during acute SARS-CoV-2 infection that could predict fatigue progression between six and 12 months post-infection in a cohort of young people with chronic fatigue following COVID-19. Data from the Long-Term Effects of COVID-19 in Adolescents (LoTECA) project were analyzed. A total of 93 participants (mean age 18.5 years, 84 % female) with chronic fatigue at six months, completed the 12-month follow-up. Multivariate analyses identified non-European ethnicity, higher interferon gamma (IFN-γ) levels, and lower RR-interval (higher resting heart rate) during acute infection as significant predictors of fatigue progression from six to 12 months. These three factors explained 21 % of the variance in the fatigue score, highlighting the importance of ethnicity, immune response, and autonomic function in the trajectory of long COVID fatigue. Early identification and targeted interventions, particularly for ethnic minorities and those with specific immune or autonomic markers during acute infection, may be helpful in reducing long-term fatigue. Further research is needed to explore treatment strategies for affected young populations.}, } @article {pmid40217361, year = {2024}, author = {Hao, X and Zhang, Q and Zhong, C and Li, E and Jiang, Y and Xu, J and Li, Y and Zhou, D and Yan, B}, title = {Frequency and risk factors of psychological distress among individuals with epilepsy before and during the outbreak of the SARS-CoV-2 Omicron variant in China: an online questionnaire survey.}, journal = {Acta epileptologica}, volume = {6}, number = {1}, pages = {2}, pmid = {40217361}, issn = {2524-4434}, support = {2022YFC2503801//the National Key R&D Program of China/ ; 2023-110//the Cadre Health Care Project of the Sichuan Provincial Department of Health/ ; HXHL21032//West China Nursing Discipline Development Special Fund Project, Sichuan University/ ; }, abstract = {BACKGROUND: The COVID-19 pandemic substantially increases the risk of severe psychological distress among people with epilepsy (PWE), especially those with monthly household income < 5000 RMB or with uncontrolled seizures. Patients with Kessler scores > 12 should consult a psychiatrist, especially during major disasters. This study was aimed to compare the frequency of psychological distress among Chinese PWE before and during the outbreak of the SARS-CoV-2 Omicron variant, and to identify risk factors for such distress.

METHODS: In this prospective study, we collected sociodemographic data of PWE aged > 14 years, who were treated at our center during December 1 to 15, 2022. All participants completed the 6-item Kessler Psychological Distress Scale before the outbreak and again during the outbreak. Health visitors who were unrelated to those patients during the outbreak were included as a control. Multivariate logistic regression analysis was performed to identify risk factors of severe psychological distress and its exacerbation.

RESULTS: Of the 223 PWE, 127 were tested positive for SARS-CoV-2, while 174 of 218 controls were positive for SARS-CoV-2. The neurological symptoms were similar between PWE and controls with SARS-CoV-2. The average Kessler score of PWE was significantly higher during the outbreak than before it (9.93 ± 3.98 vs. 8.52 ± 0.23, P < 0.001). The average score of controls during the outbreak (5.146 ± 0.35, P < 0.001) was significantly lower than that of the PWE. We identified three independent predictors for severe psychological distress in PWE during the outbreak, i.e., monthly household income < 5000 RMB (OR = 0.252, 95%CI 0.064-0.998, P = 0.048), severe psychological distress before the outbreak (OR = 0.067, 95%CI 0.026-0.174, P < 0.001), and seizure onset within 30 days before the assessment during the outbreak (OR = 0.356, 95%CI 0.157-0.805, P = 0.013). Of the three predictors, the last one was also an independent predictor for exacerbation of psychological distress during the outbreak (OR = 0.302, 95%CI 0.123-0.741, P = 0.009).

CONCLUSIONS: Our analysis suggests that the COVID-19 pandemic has substantially increased psychological distress of individuals with epilepsy, regardless of the viral infection or not. Various neurological symptoms similar to those of "long COVID" appeared for the first time among these individuals during the Omicron outbreak, highlighting the need for clinicians to screen carefully for this condition. Management of epilepsy during the pandemic or a similar major disaster should focus on the control of seizures and maintenance of mental health, especially among those with monthly household incomes below 5000 RMB, suffering uncontrolled seizures and having a history of severe psychological distress.}, } @article {pmid40212158, year = {2025}, author = {Abbas, AH and Haji, MR and Shimal, AA and Kurmasha, YH and Al-Janabi, AAH and Azeez, ZT and Al-Ali, ARS and Al-Najati, HMH and Al-Waeli, ARA and Abdulhadi, NASA and Al-Tuaama, AZH and Al-Ashtary, MM and Hussin, OA}, title = {A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {4}, pages = {2105-2117}, pmid = {40212158}, issn = {2049-0801}, abstract = {Long COVID has emerged as a significant challenge since the COVID-19 pandemic, which was declared as an outbreak in March 2020, marked by diverse symptoms and prolonged duration of disease. Defined by the WHO as symptoms persisting or emerging for at least two months post-SARS-CoV-2 infection without an alternative cause, its prevalence varies globally, with estimates of 10-20% in Europe, 7.3% in the USA, and 3.0% in the UK. The condition's etiology remains unclear, involving factors, such as renin-angiotensin system overactivation, persistent viral reservoirs, immune dysregulation, and autoantibodies. Reactivated viruses, like EBV and HSV-6, alongside epigenetic alterations, exacerbate mitochondrial dysfunction and energy imbalance. Emerging evidence links SARS-CoV-2 to chromatin and gut microbiome changes, further influencing long-term health impacts. Diagnosis of long COVID requires detailed systemic evaluation through medical history and physical examination. Management is highly individualized, focusing mainly on the patient's symptoms and affected systems. A multidisciplinary approach is essential, integrating diverse perspectives to address systemic manifestations, underlying mechanisms, and therapeutic strategies. Enhanced understanding of long COVID's pathophysiology and clinical features is critical to improving patient outcomes and quality of life. With a growing number of cases expected globally, advancing research and disseminating knowledge on long COVID remain vital for developing effective diagnostic and management frameworks, ultimately supporting better care for affected individuals.}, } @article {pmid40212085, year = {2025}, author = {Marques, JG and de Carvalho, BM and Guedes, LA and Costa-Abreu, MD}, title = {Pattern recognition in SARS cases: insights from t-SNE and k-means clustering applied to COVID-19 symptomatology.}, journal = {Frontiers in artificial intelligence}, volume = {8}, number = {}, pages = {1536486}, pmid = {40212085}, issn = {2624-8212}, abstract = {INTRODUCTION: Despite the end of the SARS-CoV-2 pandemic, the medical field continues to address several lasting effects, the most notable being long COVID. However, COVID-19 presents another specific challenge that complicates diagnosis: the similarity of its symptoms with those of other viral diseases, particularly among various SARS strains. This overlap makes it difficult to identify distinct and meaningful symptom patterns as they develop. This study proposes a dimensionality reduction approach combined with a clustering technique to visually analyse structural similarities among SARS-infected individuals, aiming to determine whether aspects such as case progression and diagnosis impact these patterns.

METHODS: This analysis utilised the t-Distributed Stochastic Neighbour Embedding (t-SNE) algorithm for dimensionality reduction, combined with Gower's distance to handle categorical data, and k-means clustering. The study focused on symptoms, case progression, and diagnoses of SARS-CoV-2 and unspecified SARS cases using data from the Brazilian SARS dataset for São Paulo State during 2020 and 2021. The process began with a visual analysis aimed at identifying structural patterns in the symptom data, highlighting potential similarities between COVID-19 patients and those diagnosed with unspecified SARS. Following this, an intra-cluster analysis was performed to investigate the common features that defined each cluster, providing insights into shared characteristics among grouped individuals.

RESULTS: The analysis revealed that both diagnoses share substantial similarities, particularly in the presence or absence of COVID-19-related symptoms, even when the majority of individuals were diagnosed with unspecified SARS.

DISCUSSION: The analysis is crucial, as Brazil was one of the countries most severely affected by the pandemic, experiencing profound impacts across multiple dimensions.}, } @article {pmid40211768, year = {2025}, author = {Gao, J and Zhao, D and Nouri, HR and Chu, HW and Huang, H}, title = {Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.}, journal = {Immunological reviews}, volume = {331}, number = {1}, pages = {e70026}, doi = {10.1111/imr.70026}, pmid = {40211768}, issn = {1600-065X}, support = {R01AI083986/NH/NIH HHS/United States ; R01AI107022/NH/NIH HHS/United States ; R01AI150082/NH/NIH HHS/United States ; R01AI152504/NH/NIH HHS/United States ; R01AI161296/NH/NIH HHS/United States ; U19AI125357/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Mast Cells/immunology/metabolism ; Cell Differentiation/genetics ; Mice ; *Lung/immunology ; Gene Expression Regulation ; Inflammation/immunology ; *COVID-19/immunology ; Transcription Factors/metabolism ; *SARS-CoV-2/immunology ; }, abstract = {Mast cells (MCs) play a critical role in allergic inflammation, anaphylaxis, and chronic inflammatory diseases such as asthma, COPD, and osteoarthritis. Dysregulated MC activation can lead to MC activation syndrome (MACS), which is observed in patients with long COVID. MCs express the high-affinity receptor for IgE and, upon activation, release mediators and cytokines that trigger anaphylactic shock and promote allergic inflammation. They also interact with epithelial and nerve cells, which are crucial in forming a complex network of cell-cell and gene-gene interactions driving chronic inflammation that can confer resistance to treatment. In this review, in the context of the literature, we focus on experiments conducted in our laboratory investigating how transcription factors and enhancers regulate genes critical in mouse MC differentiation and function related to human lung inflammation.}, } @article {pmid40211686, year = {2025}, author = {Wohlrab, F and Eltity, M and Ufer, F and Paul, F and Scheibenbogen, C and Bellmann-Strobl, J}, title = {Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2025.2492774}, pmid = {40211686}, issn = {1744-7682}, } @article {pmid40211079, year = {2025}, author = {Graham, F}, title = {Daily briefing: Long-COVID activists fought Trump research cuts and won - for now.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-025-01115-x}, pmid = {40211079}, issn = {1476-4687}, } @article {pmid40210986, year = {2025}, author = {Powers, JP and McIntee, TJ and Bhatia, A and Madlock-Brown, CR and Seltzer, J and Sekar, A and Jain, N and Hornig, M and Seibert, E and Leese, PJ and Haendel, M and Moffitt, R and Pfaff, ER and , }, title = {Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort.}, journal = {Communications medicine}, volume = {5}, number = {1}, pages = {109}, pmid = {40210986}, issn = {2730-664X}, abstract = {BACKGROUND: Shared symptoms and biological abnormalities between post-acute sequelae of SARS-CoV-2 infection (PASC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could suggest common pathophysiological bases and would support coordinated treatment efforts. Empirical studies comparing these syndromes are needed to better understand their commonalities and differences.

METHODS: We analyzed electronic health record data from 6.5 million adult patients from the National COVID Cohort Collaborative. PASC and ME/CFS diagnostic groups were defined based on recorded diagnoses, and other recorded conditions within the two groups were used to train separate machine learning-driven computable phenotypes (CPs). The most predictive conditions for each CP were examined and compared, and the overlap of patients labeled by each CP was examined. Condition records from the diagnostic groups were also used to statistically derive condition clusters. Rates of subphenotypes based on these clusters were compared between PASC and ME/CFS groups.

RESULTS: Approximately half of patients labeled by one CP are also labeled by the other. Dyspnea, fatigue, and cognitive impairment are the most-predictive conditions shared by both CPs, whereas other most-predictive conditions are specific to one CP. Recorded conditions separate into cardiopulmonary, neurological, and comorbidity clusters, with the cardiopulmonary cluster showing partial specificity for the PASC groups.

CONCLUSIONS: Data-driven approaches indicate substantial overlap in the condition records associated with PASC and ME/CFS diagnoses. Nevertheless, cardiopulmonary conditions are somewhat more commonly associated with PASC diagnosis, whereas other conditions, such as pain and sleep disturbances, are more associated with ME/CFS diagnosis. These findings suggest that symptom management approaches to these illnesses could overlap.}, } @article {pmid40210368, year = {2025}, author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM}, title = {Considerations for Long COVID Rehabilitation in Women.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {36}, number = {2}, pages = {371-387}, doi = {10.1016/j.pmr.2024.11.009}, pmid = {40210368}, issn = {1558-1381}, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.}, } @article {pmid40209192, year = {2025}, author = {Yee, B and McKenzie, F and Ellison-Loschmann, L and Russell, L and Jeffreys, M}, title = {Metabolic risk factors and long COVID: a cross-sectional study in Aotearoa New Zealand.}, journal = {The New Zealand medical journal}, volume = {138}, number = {1613}, pages = {12-23}, doi = {10.26635/6965.6699}, pmid = {40209192}, issn = {1175-8716}, support = {The Ngā Kawekawe o Mate Korona | Impacts of COVID-19 in Aotearoa study was funded by the New Zealand Ministry of Health (2021; Award number: not applicable).//New Zealand Ministry of Health/ ; }, mesh = {Humans ; New Zealand/epidemiology ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Adult ; Aged ; Risk Factors ; Body Mass Index ; SARS-CoV-2 ; Adolescent ; Hypertension/epidemiology ; Young Adult ; Diabetes Mellitus/epidemiology ; Heart Diseases/epidemiology ; }, abstract = {AIM: To describe the association between metabolic risk factors and the risk of developing long COVID in Aotearoa New Zealand.

METHODS: Individuals aged 16 years and above who had confirmed or probable COVID-19 before December 2021 were eligible for inclusion. Metabolic risk factors were high body mass index (BMI, ≥25kg/m2), high blood pressure, diabetes, heart disease and stroke. Logistic regression was used to estimate the association between metabolic risk factors and long COVID.

RESULTS: Of the 990 survey respondents, 21.9% met the definition of long COVID. After adjusting for socio-demographic factors, COVID-19 vaccination and hospitalisation, high BMI was strongly associated with long COVID (adjusted odds ratio [aOR] 2.35; 95% confidence interval [CI] 1.33-4.17, p=0.003). There was a suggestion of an association between heart disease and long COVID (aOR 4.31; 95% CI 0.80-23.3, p=0.090). No other metabolic factors were associated with long COVID. Among Māori, no associations were found between high BMI and long COVID compared with underweight/normal BMI.

CONCLUSION: High BMI as a risk factor adds to accumulating evidence on the aetiology of long COVID.}, } @article {pmid40208885, year = {2025}, author = {Lorman, V and Bailey, LC and Song, X and Rao, S and Hornig, M and Utidjian, L and Razzaghi, H and Mejias, A and Leikauf, JE and Brill, SB and Allen, A and Bunnell, HT and Reedy, C and Mosa, ASM and Horne, BD and Geary, CR and Chuang, CH and Williams, DA and Christakis, DA and Chrischilles, EA and Mendonca, EA and Cowell, LG and McCorkell, L and Liu, M and Cummins, MR and Jhaveri, R and Blecker, S and Forrest, CB and , }, title = {Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program.}, journal = {PLOS digital health}, volume = {4}, number = {4}, pages = {e0000747}, pmid = {40208885}, issn = {2767-3170}, abstract = {Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.}, } @article {pmid40209255, year = {2024}, author = {Luis Del, CO and Daniela, TH and Sergio, GM and Jesús, SS and Andrés, AS and Ener, LR}, title = {Reply to the letter "Clinical and epidemiological characteristics of patients with long COVID-19 in Mexico".}, journal = {Gaceta medica de Mexico}, volume = {160}, number = {6}, pages = {653-654}, doi = {10.24875/GMM.M24000950}, pmid = {40209255}, issn = {0016-3813}, } @article {pmid40208261, year = {2025}, author = {Ioannou, GN and Berry, K and Rajeevan, N and Li, Y and Yan, L and Huang, Y and Bui, D and Hynes, DM and Rowneki, M and Hickok, A and Niederhausen, M and Shahoumian, TA and Bohnert, A and Boyko, EJ and Korpak, A and Fox, A and Baraff, A and Iwashyna, TJ and Maciejewski, ML and Smith, VA and Berkowitz, TSZ and Pura, JA and Hebert, P and Wong, ES and O'Hare, AM and Osborne, TF and Viglianti, EM and Aslan, M and Bajema, KL}, title = {Target Trial Emulation of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus No Infection and Risk of Post-Coronavirus Disease 2019 Conditions in the Omicron Variant Versus Prior Eras.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf087}, pmid = {40208261}, issn = {1537-6591}, support = {/CU/CSP VA/United States ; C19 21-278/HX/HSRD VA/United States ; //US Department of Veterans Affairs./ ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has been linked to the development of post-COVID-19 conditions (PCCs). We investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of selected PCCs or death up to 1 year after infection, separately in the wild-type (WT), Alpha-transition, Delta, and Omicron eras and by vaccination status.

METHODS: We used health records of the Veterans Health Administration to emulate a hypothetical target trial of SARS-CoV-2 infection versus no infection. Veterans who tested positive for SARS-CoV-2 between March 2020 and April 2022 (n = 430 160) were matched 1:1 to veterans who had not tested positive for SARS-CoV-2. All-cause mortality and cumulative incidence of 32 potential PCCs were ascertained at 31-180 and 181-365 days after infection or matched index date.

RESULTS: From 31 to 180 days, the cumulative incidence of death and all organ-level PCCs was greater in infected versus uninfected participants, with cumulative incidence differences lower in the Omicron than in the WT era and lower in vaccinated than in unvaccinated persons. In the Omicron era, the cumulative incidence of death and most PCCs from day 181-365 were higher in infected than in uninfected participants only among unvaccinated but not among vaccinated persons.

CONCLUSIONS: Excess burden of PCCs and mortality persisted 31-180 days after infection in the Omicron era, albeit at a lower level than in the WT and Delta eras. Excess burden of mortality and most PCCs was much lower 181-365 days after infection and was observed in the Omicron era only among unvaccinated persons, suggesting a protective effect of vaccination.}, } @article {pmid40207927, year = {2025}, author = {Liu, J and Guo, L and Zhong, J and Wu, Y and Wang, X and Tang, X and Min, K and Yang, Y and Peng, W and Wang, Q and Ding, T and Gu, X and Zhang, H and Liu, Y and Huang, C and Cao, B and Wang, J and Ren, L and Yang, J}, title = {Proteomic Analysis of 442 Clinical Plasma Samples From Individuals With Symptom Records Revealed Subtypes of Convalescent Patients Who Had COVID-19.}, journal = {Journal of medical virology}, volume = {97}, number = {4}, pages = {e70203}, doi = {10.1002/jmv.70203}, pmid = {40207927}, issn = {1096-9071}, support = {//This work was supported by grants from the National Key R&D Program of China (2023YFC2507102), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, China (CIFMS2022-I2M-1-011, CIFMS2022-I2M-2-001, CIFMS2021-I2M-1-057, CIFMS2021-I2M-1-049, CIFMS2021-I2M-1-044, CIFMS2021-I2M-1-016, CIFMS2021-I2M-1-001, 2022-I2M-CoV19-003, and CIFMS2022-I2M-JB-003), the National Natural Science Foundation of China (82341064), the Haihe Laboratory of Cell Ecosystem Innovation Fund (22HHXBSS00008 and 22HHKYZX0034), and State Key Laboratory Special Fund 2060204./ ; }, mesh = {Humans ; *COVID-19/blood ; Male ; Female ; Proteomics ; Middle Aged ; Adult ; SARS-CoV-2 ; Convalescence ; *Proteome/analysis ; Aged ; *Blood Proteins/analysis ; Young Adult ; }, abstract = {After the coronavirus disease 2019 (COVID-19) pandemic, the postacute effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have gradually attracted attention. To precisely evaluate the health status of convalescent patients with COVID-19, we analyzed symptom and proteome data of 442 plasma samples from healthy controls, hospitalized patients, and convalescent patients 6 or 12 months after SARS-CoV-2 infection. Symptoms analysis revealed distinct relationships in convalescent patients. Results of plasma protein expression levels showed that C1QA, C1QB, C2, CFH, CFHR1, and F10, which regulate the complement system and coagulation, remained highly expressed even at the 12-month follow-up compared with their levels in healthy individuals. By combining symptom and proteome data, 442 plasma samples were categorized into three subtypes: S1 (metabolism-healthy), S2 (COVID-19 retention), and S3 (long COVID). We speculated that convalescent patients reporting hair loss could have a better health status than those experiencing headaches and dyspnea. Compared to other convalescent patients, those reporting sleep disorders, appetite decrease, and muscle weakness may need more attention because they were classified into the S2 subtype, which had the most samples from hospitalized patients with COVID-19. Subtyping convalescent patients with COVID-19 may enable personalized treatments tailored to individual needs. This study provides valuable plasma proteomic datasets for further studies associated with long COVID.}, } @article {pmid40206472, year = {2025}, author = {Madenbayeva, AM and Kurmangaliyeva, SS and Urazayeva, ST and Kurmangaliyev, KB and Bazargaliyev, YS and Kudabayeva, KI}, title = {Impact of QazVac vaccination on clinical manifestations and immune responses in post-COVID syndrome: a cross-sectional study.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1556623}, pmid = {40206472}, issn = {2296-858X}, abstract = {INTRODUCTION: Post-COVID syndrome, also known as long COVID, has emerged as a major public health concern, affecting a substantial proportion of individuals recovering from SARS-CoV-2 infection. This condition is characterized by persistent symptoms lasting at least 2 months after acute infection, significantly impacting quality of life and increasing healthcare burdens. In Kazakhstan, the recognition of post- COVID syndrome in national clinical protocols highlights the need for effective prevention and management strategies. Vaccination has been suggested as a key intervention to reduce the severity and prevalence of long COVID symptoms, yet data on its effectiveness, particularly for the domestic QazVac vaccine, remain limited. The aim of this study is to investigate the impact of vaccination with the domestic QazVac vaccine on the features of humoral and cellular immunity in patients with post-COVID conditions and to identify the leading clinical variants of the course.

METHODS: We analyzed data from 90 vaccinated and 217 non-vaccinated patients, examining sex, age, smoking status, BMI, comorbidities, and clinical manifestations.

RESULTS: There were no significant differences between the groups with regard to sex, age, and smoking status. However, the characteristics of the subjects indicated that vaccination was correlated with a lower prevalence of diabetes mellitus (2.2% vs. 11.1%, p = 0.011) and cardiovascular diseases (0.0% vs. 10.1%, p = 0.047), and a higher prevalence of hypertension among non-vaccinated subjects. With regard to clinical symptoms, vaccinated individuals presented a significantly decreased frequency of neurological (51.1% vs. 74.2%, p = 0.001), gastrointestinal (4.4% vs. 15.2%, p = 0.008), respiratory (21.1% vs. 36.4%, p = 0.009), rheumatological symptoms (26.7% vs. 38.7%, p = 0.044), and kidney symptoms (2.2% vs. 9.7%, p = 0.024). In contrast, unvaccinated participants had more memory loss (49.8% vs. 22.2%, p < 0.001), depression (31.3% vs. 6.7%, p < 0.001), joint pain (33.2% vs. 14.4%, p = 0.001), and other psychopathological symptoms.

DISCUSSION: A sharp decrease in the frequency of neurological, gastrointestinal, respiratory, and rheumatological symptoms was recorded in vaccinated patients, advocating for the protective role of vaccination against long COVID-19 sequelae. These findings highlight the potential for vaccination to mitigate the burden of post-COVID complications across various organ systems.}, } @article {pmid40206293, year = {2025}, author = {Pommy, JM and Cohen, A and Mahil, A and Glass Umfleet, L and Swanson, SJ and Franczak, M and Obarski, S and Ristow, K and Wang, Y}, title = {Changes in cerebrovascular reactivity within functional networks in older adults with long-COVID.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1504573}, pmid = {40206293}, issn = {1664-2295}, abstract = {INTRODUCTION: Cognitive symptoms are reported in the vast majority of individuals with long-COVID and there is growing support to suggest neurovascular mechanisms may play a role. Older adults are at increased risk for developing complications associated with COVID-19, including heightened risk for cognitive decline. Cerebrovascular Reactivity (CVR), a marker of neurovascular health, has been linked to age related cognitive decline and may play a role in long-COVID, however, this has not yet been explored.

METHODS: The present study examined group differences in CVR in 31 older adults with long-COVID compared to 31 cognitively unimpaired older adults without long-COVID symptoms. Follow up analyses were conducted to examine how CVR was associated with both subjective cognitive symptoms and neuropsychological (NP) test performance. A subject-specific approach, Distribution-Corrected Z-scores (DisCo-Z), was used.

RESULTS: Analyses revealed the long-COVID group demonstrated significantly greater incidence of extreme CVR clusters within the brain (>100 voxels) and within functional networks thought to drive attention and executive function. Extreme positive CVR clusters were positively associated with greater number of subjective cognitive symptoms and negatively correlated with NP performance.

DISCUSSION: These findings are among the first to provide a link between cognitive functioning in long-COVID and neurovascular changes relevant for aging and mechanistic studies of long-COVID.}, } @article {pmid40205590, year = {2025}, author = {Babicki, M and Kapusta, J and Kołat, D and Kałuzińska-Kołat, Ż and Mastalerz-Migas, A and Jankowski, P and Chudzik, M}, title = {Cardiac symptoms in patients 3-6 months after contracting COVID-19- data from the polish STOP-COVID registry.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {489}, pmid = {40205590}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; Retrospective Studies ; Registries ; Aged ; Adult ; Poland/epidemiology ; SARS-CoV-2 ; Fatigue ; Anxiety ; Depression/epidemiology ; Electrocardiography, Ambulatory ; Blood Pressure Monitoring, Ambulatory ; Echocardiography ; }, abstract = {BACKGROUND: Common complaints of long COVID patients are cardiac symptoms such as fatigue, weakness, and a feeling of palpitations. The study aimed to investigate the clinical features of patients with persistent cardiological symptoms occurring within 3 to 6 months after COVID-19. Differences in ambulatory blood pressure monitoring (ABPM), Holter ECG (electrocardiogram) and Echocardiography between people with and without persistent cardiological symptoms were evaluated. We also assessed whether the symptoms of anxiety and depression may be implicated in the clinical outcomes.

MATERIALS AND METHODS: This was a retrospective study of patients affiliated with the STOP-COVID registry who attended a follow-up visit 3-6 months after undergoing COVID-19. The visit assessed the clinical symptoms present and performed tests: ABPM, Holter ECG and Echocardiography. 504 patients additionally had GAD-2 (Generalized Anxiety Disorder 2-item) and PHQ-2 (Patient Health Questionnaire-2) tests performed.

RESULTS: The analysis included 1080 patients. At least 1 of the analyzed symptoms was present in 586 patients (54.3%). The most common symptom was fatigue (38.9%). Comparing patients with or without palpitations showed that the mean value of ventricular extrasystole was higher in the former group (p = 0.011). Comparing patients with and without cardiac symptoms, there were differences in the mean values of the PHQ-2 (p = 0.022) and GAD-2 (p < 0.001) scales, as well as in the percentage of responses related to the risk of anxiety or depression.

CONCLUSION: Cardiological symptoms are common among health issues that patients must face after contracting COVID-19. People with palpitations had more excessive ventricular extrasystoles than patients without these symptoms.

TRIAL REGISTRATION: Our retrospective study was based on analysis of medical data of patients with COVID-19 treated on out-patient basis in the STOP-COVID registry of the Polish Long-Covid Cardiovascular (PoLoCOV-CVD) study (ClinicalTrials.gov identifier- NCT05018052, the registration date 29.05.2020). Consent to conduct the study was obtained from the Bioethics Committee of the District Medical Chamber in Lodz (no. KB-0115/2021).}, } @article {pmid40205414, year = {2025}, author = {Al-Oraibi, A and Tarrant, C and Woolf, K and Nellums, LB and Pareek, M}, title = {The impact of long COVID on UK healthcare workers and their workplace: a qualitative study of healthcare workers with long COVID, their families, colleagues and managers.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {519}, pmid = {40205414}, issn = {1472-6963}, support = {2122-59//NHS Race and health observatory/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Qualitative Research ; *Health Personnel/psychology ; Female ; Male ; United Kingdom/epidemiology ; Adult ; *Workplace/psychology ; Middle Aged ; SARS-CoV-2 ; Adaptation, Psychological ; Interviews as Topic ; Family/psychology ; }, abstract = {BACKGROUND: Healthcare workers (HCWs) have been particularly impacted by long COVID, with negative effects on their work patterns and wellbeing. The aim of this study was to explore the intersection between work and long COVID for HCWs, to understand the impact of long COVID on their professional identify, their orientation to work, their wellbeing as professionals, and support needs and strategies for them as well as their managers to continue to work.

METHODS: This qualitative study was conducted through semi-structured online interviews with three groups: HCWs with long COVID, their support network members, and healthcare managers between March 2023 and May 2024. To maintain confidentiality and address concerns about workplace stigma, healthcare managers were not matched with specific HCWs. Participants were recruited through purposive and snowball sampling, until data saturation was reached, defined as the point at which no new insights or themes were identified. Data were analysed using reflexive thematic analysis.

RESULTS: A total of 42 participants were interviewed from three groups, comprising 24 HCWs, five support network members, and 13 healthcare managers. Four key themes were identified describing experiences of long COVID for HCWs: (1) Living and coping with long COVID as a HCW, (2) Workplace impact and adjustments, (3) The uncertain nature of long COVID and challenges of the definition, and (4) Feelings of guilt, stigma and blame.

CONCLUSION: In conclusion, long COVID has created significant challenges not only for HCWs but also for their managers, who struggled with staffing shortages and lack of clear guidance, and support network members who experienced emotional strain while providing care. The combination of these challenges threatens NHS workforce stability and service delivery. Developing and embedding flexible, standardised workplace interventions-such as phased return-to-work policies and tailored occupational health support-could mitigate these impacts and inform scalable solutions across diverse healthcare systems. Enhanced training for healthcare managers and further research into culturally diverse coping mechanisms could improve support for affected HCWs, reduce stigma, and contribute to a more stable and resilient healthcare workforce. While based in the UK, these findings offer important insights for health systems globally that are grappling with the long-term workforce implications of long COVID.}, } @article {pmid40202056, year = {2025}, author = {Jawad, F and Jawad, AS}, title = {Low muscle mass and the risk of long COVID.}, journal = {Journal of the Royal Society of Medicine}, volume = {}, number = {}, pages = {1410768251326488}, doi = {10.1177/01410768251326488}, pmid = {40202056}, issn = {1758-1095}, } @article {pmid40200747, year = {2025}, author = {MacLean, A and Driessen, A and Hinton, L and Nettleton, S and Wild, C and Anderson, E and Brown, A and Hoddinott, P and O'Dwyer, C and Ziebland, S and Hunt, K}, title = {Rethinking 'Recovery': A Comparative Qualitative Analysis of Experiences of Intensive Care With COVID and Long Covid in the United Kingdom.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70253}, pmid = {40200747}, issn = {1369-7625}, support = {//This study was supported by Economic and Social Research Council (EP/V039083/1 COVID), National Institute for Health Research (COV-LT2-0005), Scotland's Chief Scientist Office (COV/LTE/20/04), and Health Foundation./ ; }, mesh = {Humans ; *COVID-19/psychology/therapy ; United Kingdom/epidemiology ; Qualitative Research ; Female ; Male ; Middle Aged ; Intensive Care Units ; Adult ; Aged ; *Critical Care/psychology ; Interviews as Topic ; SARS-CoV-2 ; Adaptation, Psychological ; }, abstract = {INTRODUCTION: Interpretations of 'recovery' from illness are complex and influenced by many factors, not least patient expectations and experiences. This paper examines meanings of 'recovery', and how it is strived towards, drawing on the example of COVID-19 infection.

METHODS: Drawing on qualitative interviews (n = 93) conducted in the UK between February 2021 and July 2022, we compare adults' accounts of being admitted to an Intensive Care Unit (ICU) with COVID-19 to accounts of being ill with Long COVID, defined as ongoing symptoms for at least 12 weeks postinfection. We conducted a multi-stage comparative analysis using Nvivo to organise and code the data.

RESULTS: We identified similarities and differences in participants' descriptions of their 'worlds of illness'. For both groups, perceptions of recovery were shaped by the novel, unknown nature of COVID-19. Participants questioned the achievability of full restoration of prior states of health, highlighted the heterogeneity of 'recovery trajectories' and described the hard physical and emotional work of adjusting to changed selves. Themes that revealed differences in 'worlds of illness' described included the different baselines, waymarkers, and pathways of illness experiences. Differences in other people's responses to their illness were also evident. For ICU participants, hospitalisation, and especially ICU admission, conferred legitimate patient status and authenticity to their symptoms. Family, friends and healthcare professionals acknowledged their illness, celebrated their survival, and granted them latitude to recover. For Long Covid participants, their patient status often lacked comparable authenticity in others' eyes. They reported encountering a lack of recognition and understanding of their ongoing need to recover.

CONCLUSIONS: This study highlights how the meanings of illness ascribed by others can influence how recovery is experienced. Our findings highlight the importance of ensuring people are made to feel their illness experiences are legitimate, regardless of hospitalisation status, formal diagnosis or lack of medical knowledge and pathways. They also indicate the value of emphasising the different permutations, and lack of linearity, that recovery can take. This may help to help to guard against a lack of understanding for experiences of recovery which do not meet idealised notions.

Both studies were guided by an advisory panel that included patient and public involvement representatives with lived experience of Intensive Care/COVID experience and Long COVID respectively. Through regular meetings with the research teams, the advisory panel had input into all aspects of the study conduct, including recruitment methods and content of the interview topic guide and feedback on preliminary analyses. The Long COVID study also included a lived experience coinvestigator who contributed to data interpretation and analysis.}, } @article {pmid40200524, year = {2025}, author = {Bilionis, I and Quer Palomas, S and Vidal-Alaball, J}, title = {Digital Health for Tracking Long-Covid Symptoms with Data Insights from Mobile App Questionnaires and Wearable Devices.}, journal = {Studies in health technology and informatics}, volume = {323}, number = {}, pages = {434-438}, doi = {10.3233/SHTI250127}, pmid = {40200524}, issn = {1879-8365}, mesh = {Humans ; *Wearable Electronic Devices ; *COVID-19/diagnosis/complications/physiopathology ; *Mobile Applications ; Surveys and Questionnaires ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Telemedicine ; Digital Health ; }, abstract = {With the ongoing mutations of COVID-19 leaving many survivors with debilitating symptoms known as Long-Covid, countless individuals are struggling with persistent fatigue, cognitive impairments, and respiratory issues that can last for months or even years, profoundly disrupting their daily lives and rendering them unable to return to work or engage in social activities. Thus, this paper develops a comprehensive methodology that integrates wearable biometric data and patient-reported outcomes to enhance the monitoring and management of Long-Covid symptoms, desgined to support patient care and quality of life. The methodology involved collecting biometric data from wearable devices and psychometric assessments through mobile app questionnaires, and modeling them using mixed linear regression. Results indicated that variations in heart rate and physical activity levels were significant predictors of fatigue, stress, and pain, with lower morning activity linked to increased anxiety and pain. Additionally, participant feedback highlighted the mobile app's user-friendliness and effectiveness in tracking symptoms. Integrating wearable technology with psychological assessments in clinical practice can facilitate accurate symptom tracking and personalized interventions for individuals suffering from Long-Covid, ultimately improving patient outcomes and overall health management.}, } @article {pmid40200480, year = {2025}, author = {Finkelstein, J and Gabriel, AS and Tsai, TY and Reategui-Rivera, CM and Rocco, P and Smiley, A and Powers, C and Brown, JP}, title = {A Wearable Solution for Managing POTS: Patient Perspectives on Real-Time Heart Rate Monitoring and Activity Pacing.}, journal = {Studies in health technology and informatics}, volume = {323}, number = {}, pages = {226-230}, doi = {10.3233/SHTI250083}, pmid = {40200480}, issn = {1879-8365}, mesh = {Humans ; *Wearable Electronic Devices ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/therapy/physiopathology ; Female ; Male ; *Heart Rate ; *Mobile Applications ; Adult ; *Self Care/methods ; *Monitoring, Ambulatory/instrumentation ; }, abstract = {Managing postural tachycardia syndrome (POTS) requires continuous symptom monitoring, yet effective tools for patient self-management are limited. This study assessed patient perspectives on a wearable app designed for POTS management. Participants valued features like real-time heart rate monitoring and symptom tracking, which reduced cognitive strain and fostered confidence. Challenges such as navigation and alert management highlighted the need for improved interface design and customization. These findings demonstrate the app's potential to enhance self-management and foster patient autonomy. Future research should examine long-term outcomes and integrate suggested improvements to optimize patient-centered POTS care.}, } @article {pmid40200430, year = {2025}, author = {Yamashita, LD and Desai, N and Manning, AR and Pileggi, C and Peskin, SM and Sandsmark, DK and Kolson, DL and Schindler, MK}, title = {Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic.}, journal = {Annals of clinical and translational neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acn3.70031}, pmid = {40200430}, issn = {2328-9503}, abstract = {OBJECTIVE: To report Long COVID characteristics and longitudinal courses of patients evaluated between 4/14/21-4/14/22 at the University of Pennsylvania Neurological COVID Clinic (PNCC), including clinical symptoms, neurological examination findings, and neurocognitive screening tests from a standardized PNCC neurological evaluation approach.

METHODS: This is a retrospective cross-sectional and longitudinal study in a single-center tertiary care academic center. Participants include 240 patients with documented evidence of a positive SARS-CoV-2 PCR or antibody test who underwent initial evaluation and 182 patients with longitudinal follow-up. Main outcomes evaluated are patient demographics, duration of illness prior to self-reported improvement, and cognitive testing results-including the Montreal Cognitive Assessment (version 8.2) (MoCA) and Oral Trail Making Test-B (OTMT-B).

RESULTS: The majority (73%) of patients did not require hospitalization for their acute COVID-19 symptoms. Frequent Long COVID complaints included headache (60%), dizziness/vertigo (40%), and disturbance of taste/smell (40%). Almost all (94%) patients reported cognitive symptoms, and over 30% of patients had abnormal scores on cognitive testing. Severe infection, fewer years of education level, and non-White race were found to be statistically associated with an increased likelihood of having abnormal scores on cognitive testing. Neuroimaging and clinical laboratory testing were largely not informative for patient care. Sixty-two percent of patients with follow-up visits self-reported improvement in their primary neurological complaint within 1 year of evaluation.

INTERPRETATION: Performance on standardized cognitive screening tests may not be consistent with frequently reported cognitive complaints in Long COVID patients. The most common clinical trajectory was self-reported improvement in the primary neurological symptom.}, } @article {pmid40200197, year = {2025}, author = {Wu, JI and Lee, SH and Chen, PJ}, title = {Case report: post COVID-19 encephalopathy and oral cenesthopathy.}, journal = {BMC psychiatry}, volume = {25}, number = {1}, pages = {351}, pmid = {40200197}, issn = {1471-244X}, mesh = {Humans ; Female ; Aged ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology ; *Brain Diseases/etiology/drug therapy ; *Delusions/etiology/drug therapy ; *Depressive Disorder, Major/etiology/drug therapy ; Aripiprazole/therapeutic use ; Carbamazepine/therapeutic use ; SARS-CoV-2 ; }, abstract = {Post-COVID-19 encephalopathy is a neurological complication characterized by cognitive impairment, memory loss, and other neuropsychiatric symptoms in COVID-19 survivors. Oral cenesthopathy, a rare somatic delusion characterized by unusual oral sensations without physical findings, is typically associated with affective disorders and schizophrenia. This case report describes a 73-year-old female who developed post-COVID-19 encephalopathy, presenting initially with cognitive decline, followed by major depression and oral cenesthopathy 16 months after the infection. Comprehensive investigations excluded autoimmune encephalitis, Creutzfeldt-Jakob disease, and other structural or vascular abnormalities. Treatment with Aripiprazole and Carbamazepine resulted in partial improvement, though symptom control was limited by medication side effects. This case represents a rare presentation of long COVID syndrome, highlighting the complex neuropsychiatric sequelae of COVID-19. Further research is needed to explore the pathophysiology, treatment strategies, and long-term impacts of such manifestations.}, } @article {pmid40199960, year = {2025}, author = {Kim, D}, title = {A nationwide study of risk factors for long COVID and its economic and mental health consequences in the United States.}, journal = {Communications medicine}, volume = {5}, number = {1}, pages = {104}, pmid = {40199960}, issn = {2730-664X}, abstract = {BACKGROUND: In the United States, concerns have been increasingly raised over the future public health and economic burden of long COVID including disability and declines in labor force participation. However, only a handful of U.S. studies have explored sociodemographic or socioeconomic characteristics that put people at risk of long COVID or have investigated its economic and mental health sequelae.

METHODS: Using repeated cross-sectional data on over 375,000 adults including nearly 50,000 adults with long COVID pooled from U.S. nationally-representative Household Pulse Survey data collected between September and November 2022 and between August and October 2023, I fit age- and gender-adjusted and multivariable modified Poisson regression models to examine multiple sociodemographic and socioeconomic factors as predictors of long COVID. I further estimate the risks of unemployment, financial hardship, and anxiety and depression among working-aged adults and adults with current long COVID symptoms, and estimate the economic burden of lost wages due to long COVID.

RESULTS: Nearly one in seven adults (~35 million) and working-aged adults (~30 million) reported having a history of long COVID by late 2022 and late 2023. In age- and gender-adjusted models and fully-adjusted multivariable models, I find several factors predict long COVID including lower household income, and being Hispanic, female, gay/lesbian or bisexual. I also find having long COVID is linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships.

CONCLUSIONS: Overall, an estimated 24 million working-aged adults with long COVID had been or may still be at risk of adverse socioeconomic and mental health outcomes. The lost earnings due to long COVID among working-aged adults are estimated to total $211 billion in 2022 and $218 billion in 2023. These findings highlight the substantial public health and economic implications of long COVID among Americans.}, } @article {pmid40199308, year = {2024}, author = {Bona, JP}, title = {Knowledge Representation and Management in the Age of Long Covid and Large Language Models: a 2022-2023 Survey.}, journal = {Yearbook of medical informatics}, volume = {33}, number = {1}, pages = {216-222}, doi = {10.1055/s-0044-1800747}, pmid = {40199308}, issn = {2364-0502}, mesh = {*COVID-19 ; Humans ; *Artificial Intelligence ; *Language ; Surveys and Questionnaires ; Large Language Models ; }, abstract = {OBJECTIVES: To select, present, and summarize cutting edge work in the field of Knowledge Representation and Management (KRM) published in 2022 and 2023.

METHODS: A comprehensive set of KRM-relevant articles published in 2022 and 2023 was retrieved by querying PubMed. Topic modeling with Latent Dirichlet Allocation was used to further refine this query and suggest areas of focus. Selected articles were chosen based on a review of their title and abstract.

RESULTS: An initial set of 8,706 publications were retrieved from PubMed. From these, fifteen papers were ultimately selected matching one of two main themes: KRM for long COVID, and KRM approaches used in combination with generative large language models.

CONCLUSIONS: This survey shows the ongoing development and versatility of KRM approaches, both to improve our understanding of a global health crisis and to augment and evaluate cutting edge technologies from other areas of artificial intelligence.}, } @article {pmid40198595, year = {2025}, author = {Erdik, B}, title = {Driving under viral impairment: Linking acute SARS-CoV-2 infections to elevated car crash risks.}, journal = {PLOS global public health}, volume = {5}, number = {4}, pages = {e0004420}, doi = {10.1371/journal.pgph.0004420}, pmid = {40198595}, issn = {2767-3375}, abstract = {This study explores the linkage between acute SARS-CoV-2 and car crashes across U.S. states, correlating with COVID-19 mitigation strategies, vaccination rates, and Long COVID prevalence. This investigation analyzed aggregate COVID-19 and car crash data spanning 2020-2023, with data collection occurring between March and May 2024. Analysis was done via a Poisson regression model, adjusted for population. Key variables included vaccination status, month-specific effects relating to initial pandemic shutdowns, and Long COVID rates. Results demonstrated a significant association between acute COVID-19 infections and an increase in car crashes, independent of Long COVID status to the tune of an OR of 1.25 [1.23-1.26]. This association was observed despite varying mitigation efforts and vaccination rates across states. The study found no protective effect of vaccination against car crashes, challenging prior assumptions about the benefits of vaccination. Notably, the risk associated with COVID-19 was found to be analogous to driving impairments seen with alcohol consumption at legal limits. Findings suggest significant implications for public health policies, especially in assessing the readiness of individuals recovering from COVID-19 to engage in high-risk activities such as pilots or nuclear plant employees. Further research is necessary to establish causation and explore the exact effects of COVID-19 within the CNS affecting cognition and behavior.}, } @article {pmid40197282, year = {2025}, author = {Nguyen, ATP and Ski, CF and Thompson, DR and Abbey, SE and Kloiber, S and Sheikhan, NY and Selby, P and Shields, R and Rossell, SL and Strudwick, G and Castle, D and Hawke, LD}, title = {Health and social service provider perspectives on challenges, approaches, and recommendations for treating long COVID: a qualitative study of Canadian provider experiences.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {509}, pmid = {40197282}, issn = {1472-6963}, mesh = {Humans ; Canada ; *COVID-19/therapy/psychology ; Qualitative Research ; Female ; Middle Aged ; Male ; Adult ; *Social Work ; SARS-CoV-2 ; Interviews as Topic ; *Health Personnel/psychology ; *Attitude of Health Personnel ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {BACKGROUND: Many people who contract the SAR-CoV-2 virus present with multiple persistent and debilitating physical, cognitive and mental health symptoms that endure beyond the acute infection period. This new syndrome - generally referred to as long COVID - negatively affects patients' emotional wellbeing and quality of life, and presents a major challenge for treatment providers. Considering the lack of evidence-based treatment and supports, this qualitative descriptive study explores the experiences of Canadian health and social service providers working with individuals with long COVID, as well as their suggestions for intervention development.

METHODS: Twenty health and social service providers between the ages of 29 and 57 across Canada completed virtual individual interviews to discuss their care experiences and service recommendations for long COVID. Participants were from a range of service sectors, including primary care, rehabilitation, mental health, and community support. Interviews were recorded, transcribed, and analyzed using codebook thematic analysis.

RESULTS: Four themes illustrated providers' the experiences of (1) selecting personalized treatments based on patient presentation and similar conditions amidst uncertainty; and their recommendations for long COVID services, including (2) building an integrated and evidence-based model of care; (3) providing holistic support for patients and families through psychoeducation and daily living resources; and (4) caring for mental health in long COVID.

CONCLUSIONS: Canadian health and social service providers are adopting personalized treatment approaches to address the symptom persistence of long COVID in the face of a considerable knowledge gap. A comprehensive, integrated care pathway is needed to support patients' physical and psychosocial wellbeing while increasing provider preparedness to treat this complex condition.}, } @article {pmid40195851, year = {2025}, author = {Chung, J and Pierce, J and Franklin, C and Olson, RM and Morrison, AR and Amos-Landgraf, J}, title = {Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.}, journal = {Disease models & mechanisms}, volume = {18}, number = {9}, pages = {}, doi = {10.1242/dmm.052086}, pmid = {40195851}, issn = {1754-8411}, support = {U42OD010918//Institutes of Health (NIH)/ ; T32OD011126//NIH Office of the Director/ ; IK2BX002527//U.S. Department of Veterans Affairs/ ; }, mesh = {*COVID-19/complications/pathology/virology ; Animals ; *Disease Models, Animal ; *SARS-CoV-2/physiology ; *Gastrointestinal Diseases/virology/etiology/pathology ; Humans ; *Nervous System Diseases/virology/etiology/pathology ; *Vascular Diseases/virology/etiology ; Gastrointestinal Tract/pathology/virology ; *Translational Research, Biomedical ; }, abstract = {Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.}, } @article {pmid40195483, year = {2025}, author = {Ledford, H and Kozlov, M}, title = {Long COVID activists fought Trump team's research cuts and won - for now.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-025-00995-3}, pmid = {40195483}, issn = {1476-4687}, } @article {pmid40193038, year = {2025}, author = {Sadowski, J and Ostrowska, SA and Klaudel, T and Zaborska, M and Chruszcz, M and Sztangreciak-Lehun, A and Bułdak, RJ}, title = {Neuropsychiatric disorders in the course to SARS-CoV-2 virus infection, including biological pathomechanisms, psychosocial factors and long COVID-19 associated with "brain fog".}, journal = {Journal of neurovirology}, volume = {}, number = {}, pages = {}, pmid = {40193038}, issn = {1538-2443}, abstract = {During the COVID-19 pandemic, neuropsychiatric disorders began to be observed in a significant proportion of patients, occurring at different times after infection and characterised by varying degrees of severity. This article discusses neurological and psychiatric disorders associated with SARS-CoV-2 virus infection, taking into account biological pathomechanisms and psychosocial factors. The long COVID-19 along with the "brain fog" phenomenon were considered in the study. The purpose of the study is to analyse and discuss the available information from the scientific literature on the possible association between SARS-CoV-2 virus infection and the occurrence of neuropsychiatric disorders with different degrees of severity and temporal correlation. To discuss the correlation of COVID-19 with the occurrence of neuropsychiatric disorders, a systematic literature review was conducted using the following databases: PubMed, Elsevier and Google Scholar. The following keywords were used when searching the materials used: "neuropsychiatric disorders", "COVID-19", "SARS-CoV-2", "NeuroCOVID", "cytokine storm" and "long COVID-19". Focusing on the characteristics of the materials and methods used, as well as the results obtained and conclusions reached in each article, 164 publications of research, meta-analysis, review and case reports were included in the study. Neuropsychiatric disorders resulting from SARS-CoV-2 virus infection are multifactorial in nature. The main elements responsible for the varied pattern of symptoms include direct and indirect central nervous system effects of the disease, individual patient conditions, psychosocial factors, severity of immune responses and severity of infection. The neuropsychiatric effects of SARS-CoV-2 infection can be divided into symptoms directly related to the neurological and psychiatric zones and mixed disorders.}, } @article {pmid40191609, year = {2025}, author = {Kroon, EE and Swart, Y and Scott, CJ and Scholtz, D and Olivier, DW and Moremi, KE and Venter, C and Waters, M and Oladejo, SO and Kinnear, CJ and Pretorius, E and Rajaratnam, K and Petersen, DC and Möller, M and Kotze, MJ}, title = {Assessment of physician preparedness for implementation of pathology-supported genetic testing: solution-driven post-COVID-19 survey.}, journal = {Frontiers in genetics}, volume = {16}, number = {}, pages = {1543056}, pmid = {40191609}, issn = {1664-8021}, abstract = {INTRODUCTION: Rapid advances in personalized medicine and direct-to-consumer genomic applications could increase the risk that physicians will apply genomic results inappropriately. To address a persistent lack of understanding of genomics, we implemented a pathology-supported genetic testing (PSGT) approach, guided by insights from a clinician needs assessment conducted in 2010.

METHODS: Findings from the previous clinician survey were used to develop a new patient screening tool that integrates non-communicable disease (NCD) and post-COVID-19 care pathways. In parallel to the application of this solution for stratification of patients in different treatment groups, an updated version of the original survey questionnaire was used to reassess the knowledge and willingness of healthcare professionals to apply PSGT.

RESULTS: Thirty-six respondents completed the revised needs assessment survey in October 2022, while attending a genomics session at the Annual General Practitioner Congress, Stellenbosch University, South Africa. Nearly 89% of the respondents reported having insufficient knowledge to offer genetic testing; 80% were supportive of using PSGT to differentiate inherited from lifestyle- or therapy-associated NCDs and 83.3% supported integrating wellness screening with genetic testing to identify high-risk individuals.

DISCUSSION: It appears that while clinicians are interested in learning about genomics, they continue to report significant knowledge deficits in this area, highlighting the need for targeted clinician training and tools like multidisciplinary NCD-COVID pathway analysis to improve clinical decision-making. The co-development of a genomic counseling report for ongoing studies, guided the selection of Long COVID patients for whole-genome sequencing across the illness and wellness domains.}, } @article {pmid40191594, year = {2025}, author = {Al-Hassany, L and MaassenVanDenBrink, A and Kurth, T}, title = {Sex-related differences in the association between migraine, COVID-19, and long COVID: a population-based cohort.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1547893}, pmid = {40191594}, issn = {1664-2295}, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, placed unprecedented pressure on public health systems due to its mortality and global panic-and later due to long COVID challenges. One of these long COVID symptoms, headache, often resembles migraine-like features. Migraine shares similarities with COVID-19 and long COVID, yet the influence of sex is understudied. Our primary objective was to study the interrelationship between COVID-19 and migraine prevalence, while considering sex differences. The secondary objective was to examine how long COVID symptoms (headache, anosmia, memory, and concentration problems) affect males and females with and without COVID-19 and migraine.

METHODS: All analyses were conducted using Lifelines, a prospective cohort study in the northern Netherlands. Baseline characteristics (2006-2014), self-reported migraine diagnoses (until 2021), and questionnaires on COVID-19 and long COVID symptoms (2020-2022) were collected. Logistic regression analyses were conducted to study the association between lifetime migraine and current SARS-CoV-2 infections while adjusting for age, sex, diet, educational attainment, activity, and smoking. Descriptive and sex-stratified analyses were conducted on long COVID symptoms.

RESULTS: A total of 150,507 individuals were included, of which 29,680 (19.7%) reported migraine and 120,827 (80.3%) not. A total of 1,867 individuals with migraine [6.3% of individuals with migraine, 44.0 years (IQR 36.1-50.3)] and 6,797 individuals without migraine [5.6% of individuals without migraine, 44.4 years (IQR 35.3-52.2)] reported to be SARS-CoV-2 infected. The majority of individuals with migraine consisted of females (77.0% of those with migraine vs. 54.0% of those without migraine). The adjusted odds of having SARS-CoV-2 infections was 6.3% higher among those with (a history of) migraine compared with individuals without migraine in the logistic regression model (OR = 1.06, 95% CI 1.01-1.12). A slightly higher OR was observed in females (OR = 1.08, 95% CI 1.02-1.15), and the association was not apparent in males (OR = 1.00, 95% CI 0.88-1.12). Secondary analyses revealed that individuals with both migraine and COVID-19, and females in particular, were the most frequently bothered by long COVID symptoms headache, anosmia, concentration, and memory problems. Individuals with none of these diseases were the least bothered.

CONCLUSIONS: Individuals with migraine, especially females, are slightly more likely to report and/or contract COVID-19. Those with both conditions report long COVID symptoms more frequently, suggesting a shared vulnerability or pathophysiology. This may indicate the need for clinical surveillance of migraine patients recovering from COVID-19.}, } @article {pmid40190996, year = {2025}, author = {Goosen, A and Foster-Bonds, R and Vogel, JM}, title = {Wearable Devices Enable Long COVID Patients to Decrease Symptom Severity: A Case Series From Pilot User Testing.}, journal = {Cardiopulmonary physical therapy journal}, volume = {36}, number = {2}, pages = {99-104}, pmid = {40190996}, issn = {1541-7891}, abstract = {PURPOSE: Long COVID is a debilitating condition that is estimated to affect over 65M individuals across the world after a Coronavirus Disease 2019 (COVID-19) infection and has no broadly effective treatments. People with Long COVID have reported that pacing helps manage their symptoms, but it is difficult to implement. Based on experiences in the Long COVID community, we hypothesized that wearable devices can help individuals pace and reduce their Long COVID symptom severity.

METHODS: To inform the design of a larger study, we performed user testing by distributing Garmin® devices, the study surveys and pacing educational materials to 11 individuals with Long COVID, and conducting interviews to learn about their experience.

RESULTS: Eight of the 9 (89%) individuals reported that the information provided was helpful for their symptom management, and 2 testers did not complete the final survey. Four (44%) users had not used a wearable device before and none had trouble setting up their device. Due to the limited sample size and lack of control group, generalizability is unknown.

CONCLUSIONS: The most user testers reported that the study materials were helpful for their symptom management. These results are a promising indication of the potential for wearable devices and educational materials to help individuals with Long COVID, and potentially other chronic conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), decrease symptom severity.}, } @article {pmid40190588, year = {2025}, author = {Hunter, RM and Nielsen, G and Le Novere, M and Marston, L and Lee, TC and Stone, J and Goldstein, LH and Carson, A and Holt, K and Marsden, J and Nazareth, I and Noble, H and Reuber, M and Strudwick, AM and Santana Suarez, B and Edwards, MJ}, title = {Cost Utility of Specialist Physiotherapy for Functional Motor Disorder (Physio4FMD): Economic Analysis of a Pragmatic Randomized Controlled Trial.}, journal = {Neurology. Clinical practice}, volume = {15}, number = {3}, pages = {e200465}, pmid = {40190588}, issn = {2163-0402}, abstract = {BACKGROUND AND OBJECTIVES: Functional motor disorder (FMD), a motor-dominant variant of functional neurologic disorder, is a disabling condition associated with high health and social care resource use and poor employment outcomes. Specialist physiotherapy presents a possible treatment option, but there is limited evidence for clinical effectiveness and cost-effectiveness. Physio4FMD is a multicenter randomized controlled trial of specialist physiotherapy for FMD compared with treatment as usual (TAU). The aim of the analysis was to conduct a randomized trial based on economic evaluation of specialist physiotherapy compared with TAU.

METHODS: Eleven centers in England and Scotland randomized participants 1:1 to specialist physiotherapy or TAU (referral to community neurologic physiotherapy). Participants completed the EuroQoL EQ-5D-5L, Client Service Receipt Inventory, and Work Productivity and Activity Impairment Questionnaire at baseline, 6 months, and 12 months. The mean incremental cost per quality-adjusted life year (QALY) for specialist physiotherapy compared with TAU over 12 months was calculated from a health and social care and wider societal perspective. The probability of cost-effectiveness and 95% CIs were calculated using bootstrapping.

RESULTS: The analysis included 247 participants (n = 141 for specialist physiotherapy, n = 106 for TAU). The mean cost per participant for specialist physiotherapy was £646 (SD 72) compared with £272 (SD 374) for TAU. Including the costs of treatment, the adjusted mean health and social care cost per participant at 12 months for specialist physiotherapy was £3,814 (95% CI £3,194-£4,433) compared with £3,670 (95% CI £2,931-£4,410) for TAU, with a mean incremental cost of £143 (95% CI £-825 to £1,112). There was no significant difference in QALYs over the 12-month duration of the trial (0.030, 95% CI -0.007 to 0.067). The mean incremental cost per QALY was £4,133 with an 86% probability of being cost-effective at a £20,000 threshold. When broader societal costs such as loss of productivity were taken into consideration, specialist physiotherapy was dominant (incremental cost: £-5,169, 95% CI £-15,394 to £5,056).

DISCUSSION: FMD was associated with high health and social care costs. There is a high probability that specialist physiotherapy is cost-effective compared with TAU particularly when wider societal costs are taken into account.

International Standard Randomised Controlled Trial registry, ISRCTN56136713.}, } @article {pmid40190303, year = {2025}, author = {Babicki, M and Lejawa, M and Osadnik, T and Kapusta, J and Banach, M and Jankowski, P and Mastalerz-Migas, A and Kałuzińska-Kołat, Ż and Kołat, D and Chudzik, M}, title = {LC risk score - development and evaluation of a scale for assessing the risk of developing long COVID.}, journal = {Archives of medical science : AMS}, volume = {21}, number = {1}, pages = {121-130}, pmid = {40190303}, issn = {1734-1922}, abstract = {INTRODUCTION: The aim of the study was to create a valuable practical tool for evaluating the risk of developing long COVID.

MATERIAL AND METHODS: 1150 patients from the Polish STOP-COVID registry (PoLoCOV study) were used to develop the risk score. The patients were ill between 03/2020 and 04/2022. To develop a clinically useful scoring model, the LC risk score was generated using the machine learning-based framework AutoScore. Patient data were first randomised into a training (70% of output) and a test (30% of output) cohort. Due to the relatively small study group, cross-validation was used. Model predictive ability was evaluated based on the ROC curve and the AUC value. The result of the risk score for a given patient was the total value of points assigned to selected variables.

RESULTS: To create the LC risk score, eight variables were ultimately selected due to their significance and clinical value. Female gender significantly contributed to higher final outcome values, with age range 40-49, body mass index < 18.5 kg/m[2], hospitalisation during active disease, arthralgia, myalgia as well as loss of taste and smell during infection, COVID-19 symptoms lasting at least 14 days, and unvaccinated status. The final predictive value of the developed LC risk score for a cut-off of 58 points was AUC = 0.630 (95% CI: 0.571-0.688) with sensitivity 39.80%, specificity 85.1%, positive predictive value 80.8%, and negative predictive value 47.3%.

CONCLUSIONS: The LC risk score may be a practical and undemanding utility that employs basic sociodemographic data, vaccination status, and symptoms during COVID-19 to assess the risk of long COVID.}, } @article {pmid40190125, year = {2025}, author = {Rayner, CR and Burton, K and MacDonald, EB}, title = {Guidelines for a sustainable return to work with long COVID.}, journal = {Occupational medicine (Oxford, England)}, volume = {75}, number = {1}, pages = {9-13}, doi = {10.1093/occmed/kqae141}, pmid = {40190125}, issn = {1471-8405}, } @article {pmid40189695, year = {2025}, author = {Liu, N and Deng, J and Lu, F and Xiao, J}, title = {Virtual reality enhanced mindfulness and yoga intervention for postpartum depression and anxiety in the post COVID era.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11766}, pmid = {40189695}, issn = {2045-2322}, support = {202410585011//National College Students Innovation and Entrepreneurship Training Program/ ; XGQN202303//School Management Project of Guangzhou Sport University/ ; }, mesh = {Humans ; Female ; *Yoga/psychology ; *Depression, Postpartum/therapy/psychology ; *Mindfulness/methods ; *COVID-19/psychology/epidemiology ; Adult ; *Anxiety/therapy/psychology ; *Virtual Reality ; Treatment Outcome ; SARS-CoV-2 ; Hydrocortisone/analysis ; }, abstract = {The postpartum period has witnessed increasing rates of depression and anxiety, particularly in the context of the COVID-19 pandemic, with these conditions often co-occurring and being exacerbated by the lingering effects of long COVID. Traditional interventions, such as mindfulness-based stress reduction (MBSR) and yoga, have demonstrated effectiveness in alleviating these symptoms. However, the limitations of in-person sessions, especially in the context of pandemic-related restrictions, highlight the need for accessible, innovative approaches. Integrating Virtual Reality (VR) technology with these traditional practices presents a novel solution, offering immersive, customizable environments that may enhance engagement and therapeutic outcomes. This study evaluates the effectiveness of a VR-enhanced mindfulness and yoga intervention in treating postpartum depression and anxiety in women affected by long COVID, with additional examination of underlying physiological stress markers and cognitive control mechanisms. In this randomized controlled trial, 111 postpartum women were randomly assigned to experimental (VR-enhanced intervention), control (traditional in-person sessions), or blank groups using computer-generated randomization. The 8-week intervention involved thrice-weekly 60-minute sessions. Outcomes were assessed at baseline, post-intervention, and 4-week follow-up using the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7 (GAD-7) scale, salivary cortisol measurements, and an emotional Stroop task. The VR-enhanced intervention group demonstrated significant improvements in both depression (EPDS: P < 0.001, ηp[2] = 0.18) and anxiety symptoms (GAD-7: P < 0.001, ηp[2] = 0.17), with these therapeutic effects significantly greater than those observed in the control and blank groups (P < 0.001 for both comparisons). These improvements were strongly correlated (r = 0.68, P < 0.001). Supporting these primary outcomes, salivary cortisol levels showed a significant decrease (P < 0.001, ηp[2] = 0.13), and cognitive control improved as evidenced by reduced emotional Stroop task conflict effect (P < 0.001, ηp[2] = 0.37). Correlation analysis revealed robust associations between improvements in depression and anxiety symptoms and changes in physiological markers in both short-term and long-term outcomes. This study demonstrates that integrating VR technology with traditional mindfulness and yoga practices effectively reduces both postpartum depression and anxiety symptoms in the post-COVID era. The parallel improvements in physiological stress markers and cognitive control provide insight into potential mechanisms underlying these therapeutic effects. These findings underscore the value of immersive technology in enhancing traditional therapeutic approaches for addressing postpartum depression and anxiety in the post-pandemic context.}, } @article {pmid40189508, year = {2025}, author = {Xiang, J and Zheng, H and Cai, Y and Chen, S and Wang, Y and Chen, R}, title = {Cumulative social disadvantage and its impact on long COVID: insights from a U.S. national survey.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {207}, pmid = {40189508}, issn = {1741-7015}, support = {AHWJ2023BAa20131//Health Research Program of Anhui/ ; 2024AH052585//Humanity and Social Science Research Project of Anhui Educational Committee/ ; }, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; Adult ; United States/epidemiology ; Middle Aged ; *Social Determinants of Health ; Aged ; Young Adult ; Adolescent ; *Health Status Disparities ; Health Surveys ; SARS-CoV-2 ; Socioeconomic Factors ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {BACKGROUND: The COVID-19 pandemic has exacerbated health disparities, with long COVID emerging as a major global public health challenge. Although clinical risk factors for long COVID are well-documented, the cumulative burden of adverse social determinants of health (SDoH) remains underexplored. This study aims to investigate the association between cumulative social disadvantage and long COVID.

METHODS: Using data from the 2022 and 2023 National Health Interview Survey cycles (n = 16,446 U.S.adults), cumulative social disadvantage was quantified through 18 SDoH indicators and categorized into quartiles. The highest quartile represents the most disadvantaged individuals. Long COVID was defined as self-reported symptoms persisting for three months or longer. Weighted logistic regression models were used to examine the association, adjusting for demographic and clinical variables.

RESULTS: Adults in the highest quartile of cumulative social disadvantage exhibited an increased odds of experiencing long COVID compared to those in the lowest quartile (AOR = 2.52, 95% Cl: 2.13, 2.98). This association persisted across demographic subgroups, with particularly pronounced effects among women and non-Hispanic Blacks. Hispanics and non-Hispanic Whites showed weaker, but still statistically significant. Key contributors included mental health difficulties, economic instability, and healthcare access barriers. Furthermore, cumulative social disadvantage was linked to fair or poor general health status among individuals with long COVID.

CONCLUSIONS: This study highlights the positive association between cumulative social disadvantage and long COVID. Addressing systemic inequities through integrated public health strategies is essential to mitigate the burden of long COVID and reduce social disparities in health.}, } @article {pmid40188876, year = {2025}, author = {Kattner, AA}, title = {Sacred codes: preservation, permutation and expression.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {100852}, doi = {10.1016/j.bj.2025.100852}, pmid = {40188876}, issn = {2320-2890}, abstract = {This issue of the Biomedical Journal features a special section on epigenetics in infection, exploring epitranscriptomic modifications in the malaria parasite Plasmodium and the African sleeping sickness parasite Trypanosoma, with a focus on how these modifications influence parasite development and survival strategies. Additionally, this issue reviews regulatory mechanisms in asymmetric cell division, assessment needs for children with developmental coordination disorder along with recommendations, and advancements in 3D chondrocyte culturing for tissue engineering. Also examined are three key pathways exacerbating long COVID, the increasing impact of electromagnetic exposure in built environments on human health, and recent updates in liver transplantation criteria for hepatocellular carcinoma complicated by portal vein tumor thrombosis. Research in bladder cancer investigates the role of activating transcription factor 3, known for its anti-tumor properties, and its link to metformin. Another study demonstrates the efficacy of Sanger sequencing in streamlining mitochondrial disorder diagnostics, enabling timely identification based on clinical evidence. Additional studies present a novel intervention approach for autoimmune diseases, advancements in artificial bone grafts to enhance bone regeneration, and the benefits of public hospital participation in oncological clinical trials. Finally, a study confirms the suitability of transthoracic echocardiography for diagnosing suspected acute aortic syndrome.}, } @article {pmid40188838, year = {2025}, author = {Sawano, M and Bhattacharjee, B and Caraballo, C and Khera, R and Li, SX and Herrin, J and Christian, D and Coppi, A and Warner, F and Holub, J and Henriquez, Y and Johnson, MA and Goddard, TB and Rocco, E and Hummel, AC and Mouslmani, MA and Hooper, WB and Putrino, DF and Carr, KD and Charnas, L and De Jesus, M and Nepert, D and Abreu, P and Ziegler, FW and Spertus, JA and Iwasaki, A and Krumholz, HM}, title = {Nirmatrelvir-ritonavir versus placebo-ritonavir in individuals with long COVID in the USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial.}, journal = {The Lancet. Infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1473-3099(25)00073-8}, pmid = {40188838}, issn = {1474-4457}, abstract = {BACKGROUND: The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir-ritonavir for treating long COVID.

METHODS: In this phase 2, decentralised, double-blind, randomised controlled trial, adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir-ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past 2 weeks; active liver disease; renal impairment; and immunocompromise. Using software for 1:1 stratified block random assignment, participants were randomly allocated to receive either two tablets of nirmatrelvir (150 mg each) and one tablet of ritonavir (100 mg), or placebo and one tablet of ritonavir (100 mg), orally administered twice daily for 15 days, stratified by age, sex at birth, and COVID-19 vaccination status. Participants, clinicians, and the study team were masked to treatment allocation. The primary efficacy endpoint was the change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score (PHSS) from baseline to day 28, analysed by intention to treat. Safety endpoints were reported from baseline to week 6 in all participants who were exposed to the study treatment. This trial is registered with ClinicalTrials.gov (NCT05668091) and is now closed to new participants.

FINDINGS: Between April 14, 2023, and Feb 26, 2024, 119 participants were screened. 100 were enrolled (66 [66%] female participants and 34 [34%] male participants), with 49 assigned to the nirmatrelvir-ritonavir group and 51 to the placebo-ritonavir group (intention-to-treat population). Three participants in the nirmatrelvir-ritonavir group and two in the placebo-ritonavir group withdrew before starting treatment and were excluded from the safety population. The mean PROMIS-29 PHSS at baseline was 39·6 (95% CI 37·4 to 41·9) in the nirmatrelvir-ritonavir group and 36·3 (34·4 to 38·2) in the placebo-ritonavir group. The adjusted change from baseline to day 28 was 0·45 (-0·93 to 1·83) in the nirmatrelvir-ritonavir group and 1·01 (-0·30 to 2·31) in the placebo-ritonavir group (adjusted mean difference -0·55 [95% CI -2·32 to 1·21; p=0·54]). No deaths or serious adverse events were recorded between baseline and week 6. Study drug-related treatment-emergent adverse events were reported in more participants in the nirmatrelvir-ritonavir group (35 [76%] of 46) compared with the placebo-ritonavir group (27 [55%] of 49), mostly driven by dysgeusia. Early treatment termination due to an adverse event occurred in two participants in the nirmatrelvir-ritonavir group and one in the placebo-ritonavir group.

INTERPRETATION: Nirmatrelvir-ritonavir administered for 15 days did not significantly improve health outcomes in participants with long COVID compared with placebo-ritonavir at day 28. However, the study showed the feasibility of large-scale, decentralised trials in long COVID.

FUNDING: Pfizer, Fred Cohen, and Carolyn Klebanoff.}, } @article {pmid40188835, year = {2025}, author = {Bramante, CT and Rosen, CJ}, title = {Long COVID treatment trials: still more questions than answers?.}, journal = {The Lancet. Infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1473-3099(25)00208-7}, pmid = {40188835}, issn = {1474-4457}, } @article {pmid40186736, year = {2025}, author = {Bosire, EN and Kamau, LW and Mendenhall, E}, title = {Stigma, Chronicity and Complexity of Living with Long Covid in Kenya.}, journal = {Culture, medicine and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11013-025-09906-7}, pmid = {40186736}, issn = {1573-076X}, abstract = {Living with a complex chronic illness can be debilitating as people are constantly negotiating new bodily symptoms, constant treatment-seeking, readjustments to identity and routine. In Kenya, millions of people were infected with COVID-19 and surveillance of Long Covid remains limited. We interviewed 23 Kenyans seeking medical care or social support for Long Covid to understand their lived experiences. Participants reported limited access to healthcare; they also described symptoms including disabling fatigue, memory inconsistencies, and acute pain in the muscle, gut, or tissues. However, we found a unique chronic illness stigma-where people did not want to reveal that they had Long Covid because they feared of being perceived to have HIV. Participants reported feeling dismissed or disbelieved by family, friends, and clinicians and turned to online social support groups like Facebook. While some appreciated clinicians who used experimental treatment, others expressed trepidation when treatments caused them to feel sicker. The chronicity and debilitating symptoms of Long Covid may cultivate a unique stigma around the condition and point to a normalization of Long Covid with other chronic conditions, despite limited treatments. A broader understanding of Long Covid symptoms and care must be expanded to include destigmatizing the condition in Kenya.}, } @article {pmid40186701, year = {2025}, author = {Frost, F and Rivera-Caravaca, JM and Lip, GYH}, title = {The use of oral anticoagulation at the time of acute COVID-19 infection and subsequent development of long-COVID/post-acute sequelae of SARS-CoV-2 infection.}, journal = {Journal of thrombosis and thrombolysis}, volume = {}, number = {}, pages = {}, pmid = {40186701}, issn = {1573-742X}, support = {CV185-805//Bristol Myers Squibb- Pfizer alliance/ ; }, abstract = {Long COVID (LC) or post-acute sequelae of SARS-CoV-2 infection (PASC) is defined as ongoing, relapsing or new symptoms/conditions persisting after an acute COVID-19 infection. Given the potential role of oral anticoagulants (OAC) in treating thrombotic sequelae of LC/PASC, we investigated whether prevalent OAC use at the time of acute COVID-19 infection was associated with reduced development of LC/PASC. Retrospective cohort study within the TriNetx network. The primary cohort was defined as adults with a confirmed diagnosis of COVID-19. We defined OAC users as those who had received OACs (either direct-acting OACs [DOACs] or vitamin K antagonists [VKA]) in the preceding 3-months and non-users as those without OAC use within the previous 12-months. The primary outcome was a composite of 9 features associated with LC/PASC We identified 38,409 DOAC users, 19,243 VKA users, and 2,329,771 non-OAC users with acute COVID-19 infection. After successful propensity score matching (PSM), we found an increased risk of LC/PASC features in those receiving DOAC compared to non-OAC (HR [95% CI] 1.50 [1.35 to 1.68], p < 0.0001), and in VKA users compared to non-OACs (HR [95% CI] 1.98 [1.78 to 2.20], p < 0.0001), while DOAC users were at reduced risk compared to VKA users (HR [95% CI] 0.71 [0.62 to 0.81], p < 0.0001). We found no evidence that prevalent OAC at the time of acute COVID-19 infection was associated with reduced risk of LC/PASC. Further work is needed to understand whether there is a role for OAC therapy in the management of LC/PASC.}, } @article {pmid40185235, year = {2025}, author = {Weberling, LD and Hillier, E and Friedrich, MG and Zahlten, M and Frey, N and André, F and Steen, H}, title = {Abnormal Coronary Vascular Response in Patients with Long COVID Syndrome - a Case-Control Study Using Oxygenation-Sensitive Cardiovascular Magnetic Resonance.}, journal = {Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance}, volume = {}, number = {}, pages = {101890}, doi = {10.1016/j.jocmr.2025.101890}, pmid = {40185235}, issn = {1532-429X}, abstract = {BACKGROUND: Following the world-wide COVID-19 pandemic, many patients reported ongoing severe cardiovascular symptoms after the acute phase. This multisystemic condition has been named long COVID syndrome. Whilst cardiovascular magnetic resonance (CMR) imaging is the gold standard to diagnose acute myocardial damage, no specific changes have been shown in long COVID patients. However, endothelial dysfunction has been hypothesized to contribute to its pathogenesis. Oxygenation-sensitive CMR during breathing exercise is a simple, non-invasive and accurate test to objectify vascular function, that has not been applied to long COVID patients yet.

METHODS: After receiving approval from the local ethics committee, this prospective observational case-control study enrolled (i) patients reporting symptoms for ≥6 weeks following an acute COVID-19 infection or vaccination, and (ii) healthy volunteers with neither symptoms nor history of cardiovascular disease. Participants completed a questionnaire, point-of-care testing of cardiac biomarkers, a standard non-contrast CMR and an oxygenation-sensitive CMR. Heart rate response and breathing-induced myocardial oxygenation reserve (B-MORE) were assessed during metronome-paced hyperventilation and apnea.

RESULTS: 31 patients (17 female; age 39.4 [30.3; 51.6] years) and 27 controls (12 female; age 33.3 [27.3; 46.8]) were included with comparable demographics and cardiovascular risk factors between groups. Laboratory testing and standard CMR did not reveal any pathologies in either of the groups. Indexed left ventricular stroke volume was significantly lower in patients (44.5ml [41.2; 46.6] vs. 55.9ml [49.2; 59.2]; p<0.001), whilst ejection fraction and longitudinal strain of both ventricles were comparable (p>0.05 for all). Vasoactive breathing exercises induced a significant increase in heart rate (+35/min [21; 45]) and B-MORE (9.8% [4.3; 17.2]) in controls. In patients however, heart rate increase was blunted (+15/min [7; 26]; p<0.001) and B-MORE was significantly lower (7.3% [3.4; 10.4], p=0.044).

CONCLUSIONS: This pilot study is the first to show a blunted hemodynamic and myocardial oxygenation response to vasoactive breathing maneuvers during Oxygenation-sensitive CMR in long COVID patients. This simple, non-invasive test may be the first to objectify complaints of affected patients and indicates evidence for the crucial role of the endothelium in the pathophysiology of long COVID.}, } @article {pmid40183663, year = {2025}, author = {Park, JW}, title = {Understanding and Addressing Long COVID, the Lingering Shadow of COVID-19.}, journal = {Infection & chemotherapy}, volume = {57}, number = {1}, pages = {179-180}, doi = {10.3947/ic.2025.0025}, pmid = {40183663}, issn = {2093-2340}, } @article {pmid40183655, year = {2025}, author = {Lee, SJ and Baek, YJ and Lee, SH and Kim, JH and Ahn, JY and Kim, J and Jeon, JH and Seok, H and Choi, WS and Park, DW and Choi, Y and Song, KH and Kim, ES and Kim, HB and Ko, JH and Peck, KR and Choi, JP and Kim, JH and Kim, HS and Jeong, HW and Choi, JY}, title = {Characteristics and Prevalence of Sequelae after COVID-19: A Longitudinal Cohort Study.}, journal = {Infection & chemotherapy}, volume = {57}, number = {1}, pages = {72-80}, doi = {10.3947/ic.2024.0090}, pmid = {40183655}, issn = {2093-2340}, support = {//Korea National Institute of Infectious Diseases/Korea ; /KNIH/Korea National Institute of Health/Korea ; 2021-ER1902-01/KDCA/Korea Disease Control and Prevention Agency/Korea ; RS-2024-00439160/MSIT/MSIT/Korea ; }, abstract = {BACKGROUND: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments.

MATERIALS AND METHODS: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19.

RESULTS: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05-0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00-1.09; P=0.04) showed a significant association with long COVID after 12-18 months in a multivariable logistic regression analysis.

CONCLUSION: Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.}, } @article {pmid40182854, year = {2025}, author = {Zhang, J and Chen, Y and Zhang, A and Yang, Y and Ma, L and Meng, H and Wu, J and Zhu, K and Zhang, J and Lin, K and Lin, X}, title = {Explainable machine learning model and nomogram for predicting the efficacy of Traditional Chinese Medicine in treating Long COVID: a retrospective study.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1529993}, pmid = {40182854}, issn = {2296-858X}, abstract = {INTRODUCTION: Long COVID significantly affects patients' quality of life, yet no standardized treatment has been established. Traditional Chinese Medicine (TCM) presents a promising potential approach with targeted therapeutic strategies. This study aims to develop an explainable machine learning (ML) model and nomogram to identify Long COVID patients who may benefit from TCM, enhancing clinical decision-making.

METHODS: We analyzed data from 1,331 Long COVID patients treated with TCM between December 2022 and February 2024 at three hospitals in Zhejiang, China. Effectiveness was defined as improvement in two or more symptoms or a minimum 2-point increase in the Traditional Chinese Medicine Syndrome Score (TCMSS). Data included 11 patient and disease characteristics, 18 clinical symptoms and syndrome scores, and 12 auxiliary examination indicators. The least absolute shrinkage and selection operator (LASSO) method identified features linked to TCM efficacy. Data from 1,204 patients served as the training set, while 127 patients formed the testing set.

RESULTS: We employed five ML algorithms: Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbors (KNN), Extreme Gradient Boosting (XGBoost), and Neural Network (NN). The XGBoost model achieved an Area Under the Curve (AUC) of 0.9957 and an F1 score of 0.9852 in the training set, demonstrating superior performance in the testing set with an AUC of 0.9059 and F1 score of 0.9027. Key features identified through SHapley Additive exPlanations (SHAP) included chest tightness, aversion to cold, age, TCMSS, Short Form (36) Health Survey (SF-36), C-reactive protein (CRP), and lymphocyte ratio. The logistic regression-based nomogram demonstrated an AUC of 0.9479 and F1 score of 0.9384 in the testing set.

CONCLUSION: This study utilized multicenter data and multiple ML algorithms to create a ML model for predicting TCM efficacy in Long COVID treatment. Furthermore, a logistic regression-based nomogram was developed to assist the model and improve decision-making efficiency in TCM applications for Long COVID management.}, } @article {pmid40180914, year = {2025}, author = {M Bader, S and Calleja, DJ and Devine, SM and Kuchel, NW and Lu, BGC and Wu, X and Birkinshaw, RW and Bhandari, R and Loi, K and Volpe, R and Khakham, Y and Au, AE and Blackmore, TR and Mackiewicz, L and Dayton, M and Schaefer, J and Scherer, L and Stock, AT and Cooney, JP and Schoffer, K and Maluenda, A and Kleeman, EA and Davidson, KC and Allison, CC and Ebert, G and Chen, G and Katneni, K and Klemm, TA and Nachbur, U and Georgy, SR and Czabotar, PE and Hannan, AJ and Putoczki, TL and Tanzer, M and Pellegrini, M and Lechtenberg, BC and Charman, SA and Call, MJ and Mitchell, JP and Lowes, KN and Lessene, G and Doerflinger, M and Komander, D}, title = {A novel PLpro inhibitor improves outcomes in a pre-clinical model of long COVID.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2900}, pmid = {40180914}, issn = {2041-1723}, mesh = {Animals ; *SARS-CoV-2/drug effects/enzymology ; *Antiviral Agents/pharmacology/chemistry/therapeutic use ; Mice ; Disease Models, Animal ; COVID-19/virology ; Humans ; *COVID-19 Drug Treatment ; *Coronavirus 3C Proteases/antagonists & inhibitors/metabolism ; Female ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has highlighted the vulnerability of a globally connected population to zoonotic viruses. The FDA-approved coronavirus antiviral Paxlovid targets the essential SARS-CoV-2 main protease, Mpro. Whilst effective in the acute phase of a COVID infection, Paxlovid cannot be used by all patients, can lead to viral recurrence, and does not protect against post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, an emerging significant health burden that remains poorly understood and untreated. Alternative antivirals that are addressing broader patient needs are urgently required. We here report our drug discovery efforts to target PLpro, a further essential coronaviral protease, for which we report a novel chemical scaffold that targets SARS-CoV-2 PLpro with low nanomolar activity, and which exhibits activity against PLpro of other pathogenic coronaviruses. Our lead compound shows excellent in vivo efficacy in a mouse model of severe acute disease. Importantly, our mouse model recapitulates long-term pathologies matching closely those seen in PASC patients. Our lead compound offers protection against a range of PASC symptoms in this model, prevents lung pathology and reduces brain dysfunction. This provides proof-of-principle that PLpro inhibition may have clinical relevance for PASC prevention and treatment going forward.}, } @article {pmid40180726, year = {2025}, author = {Diener, HC}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {6}, pages = {30}, doi = {10.1007/s15006-025-4871-1}, pmid = {40180726}, issn = {1613-3560}, } @article {pmid40180399, year = {2025}, author = {Mansoubi, M and Richards, T and Ainsworth-Wells, M and Fleming, R and Leveridge, P and Shepherd, C and Dawes, H}, title = {Understanding symptom clusters, diagnosis and healthcare experiences in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID: a cross-sectional survey in the UK.}, journal = {BMJ open}, volume = {15}, number = {4}, pages = {e094658}, doi = {10.1136/bmjopen-2024-094658}, pmid = {40180399}, issn = {2044-6055}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Cross-Sectional Studies ; Female ; United Kingdom/epidemiology ; *COVID-19/diagnosis/epidemiology/complications/therapy ; Male ; Adult ; Middle Aged ; SARS-CoV-2 ; Aged ; Surveys and Questionnaires ; State Medicine ; Patient Satisfaction ; }, abstract = {OBJECTIVES: This study aims to provide an in-depth analysis of the symptoms, coexisting conditions and service utilisation among people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. The major research questions include the clustering of symptoms, the relationship between key factors and diagnosis time, and the perceived impact of National Institute for Health and Care Excellence (NICE) guidelines on patient care.

DESIGN: Cross-sectional survey using secondary data analysis.

SETTING: Community-based primary care level across the UK, incorporating online survey participation.

PARTICIPANTS: A total of 10 458 individuals responded to the survey, of which 8804 confirmed that they or a close friend/family member had ME/CFS or long COVID. The majority of respondents were female (83.4%), with participants from diverse regions of the UK.

Primary outcomes included prevalence and clustering of symptoms, time to diagnosis, and participant satisfaction with National Health Service (NHS) care, while secondary outcomes focused on symptom management strategies and the perceived effect of NICE guidelines.

RESULTS: Fatigue (88.2%), postexertional malaise (78.2%), cognitive dysfunction (88.4%), pain (87.6%) and sleep disturbances (88.2%) were the most commonly reported symptoms among participants with ME/CFS, with similar patterns observed in long COVID. Time to diagnosis for ME/CFS ranged widely, with 22.1% diagnosed within 1-2 years of symptom onset and 12.9% taking more than 10 years. Despite updated NICE guidelines, only 10.1% of participants reported a positive impact on care, and satisfaction with NHS services remained low (6.9% for ME/CFS and 14.4% for long COVID).

CONCLUSIONS: ME/CFS and long COVID share overlapping but distinct symptom clusters, indicating common challenges in management. The findings highlight significant delays in diagnosis and low satisfaction with specialist services, suggesting a need for improved self-management resources and better-coordinated care across the NHS.}, } @article {pmid40180332, year = {2025}, author = {Yang, OO}, title = {The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {}, number = {}, pages = {}, doi = {10.1093/jimmun/vkaf033}, pmid = {40180332}, issn = {1550-6606}, abstract = {This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.}, } @article {pmid40179895, year = {2025}, author = {Frank, T and Bruckmann, P and Binneböse, M and Wallis, H and Elgner, M and Junne, F and Massag, J and Mikolajczyk, R and Schurr, M and Giel, K and Wedekind, L and Kuhn, J and Gündel, H and Müller, AM and Beckmann, P and Lahmann, C and Allwang, C}, title = {[Psychosocial aspects of Long COVID - A psychotherapeutic treatment manual from the PsyLoCo project].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {75}, number = {3-04}, pages = {127-131}, doi = {10.1055/a-2535-0607}, pmid = {40179895}, issn = {1439-1058}, mesh = {Humans ; *COVID-19/psychology/complications/therapy ; *Psychotherapy/methods ; Adaptation, Psychological ; Pilot Projects ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *Manuals as Topic ; Fatigue/therapy/etiology/psychology ; }, abstract = {Long COVID describes long-term health sequelae after a SARS-CoV-2 infection. Despite various theoretical approaches, the pathogenesis of long COVID is not yet fully understood and the diagnostic criteria are vague. This makes the development of targeted, cause-specific therapies challenging. In addition to the symptoms, many patients suffer from various psychosocial burdens and a significantly reduced quality of life. In order to address this, psychosomatic or psychotherapeutic interventions should be used in addition to symptom-oriented treatment. Within the PsyLoCo project, a psychotherapeutic treatment manual was developed that is tailored to the specific needs of long COVID patients. In four modules, it addresses (1) coping and distress management, (2) physical complaints and pain, (3) chronic fatigue and affective symptoms and (4) social and working life. The manual was tested for feasibility and effectiveness in a multicentre, randomized controlled pilot study. The contents of this treatment manual are presented below.}, } @article {pmid40178459, year = {2025}, author = {Goddings, AL and Johnston, R and Wortley, E and Patel, R and Boyd, H and Newlands, F and Shafran, R and Baig, B and Whittaker, E and Segal, TY}, title = {Characterisation and Management of Children and Young People Referred to a Paediatric Tertiary Post-COVID Service.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jadohealth.2025.01.026}, pmid = {40178459}, issn = {1879-1972}, abstract = {PURPOSE: Post-COVID condition (PCC) emerged following the 2020 coronavirus pandemic and required rapid service development to manage affected patients. This evaluation describes the demographics, medical background, management and six-month outcomes of children and young people with PCC-related symptoms referred to one specialist tertiary service between June 2020 and August 2022.

METHODS: Data were retrospectively collected from referral information and medical notes.

RESULTS: 176 patients (61% female) aged 6-18 years were referred, with a mean 8.2 PCC-related symptoms impacting on functioning (97%) and school attendance (86%). 10% patients had an autistic spectrum disorder diagnosis, above the ∼2% national prevalence, while rates of atopy and mental health were similar to national prevalence. 59% patients were managed in specialist tertiary clinics by clinicians with input from allied health professionals. At 6 month review, 40/73 patients reported improvement in their daily functioning, with 30/73 reporting no change and 3/73 reporting functional deterioration. School attendance increased over 6 months for 43/67 patients, with 12/67 reporting no change and 4/67 reporting reduced school attendance.

DISCUSSION: Patients referred for PCC-related specialist input have significant functional impairment and challenges accessing education. More than half of those seen in specialist clinics showed functional improvement and increased school attendance over 6 months, while a subgroup had persistent symptoms. This suggests that the service model is beneficial for this complex patient group overall, although needs to be resourced for longer input for some. Further work is needed to understand the variability in presentation and symptom course.}, } @article {pmid40177288, year = {2025}, author = {Meo, MOS and AlHusseini, N and Ibrahim, DI and Meo, MZS and Ahsan, F and Tamim, H and Sajid, MR}, title = {Clinical manifestations of Long-COVID: an observational perspective.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1523817}, doi = {10.3389/fmed.2025.1523817}, pmid = {40177288}, issn = {2296-858X}, abstract = {OBJECTIVES: Coronavirus Disease-19, also known as COVID-19, resulted in a pandemic that caused massive health concerns and economic losses globally. Worldwide, people are still facing persistent clinical symptoms following COVID-19 infection, characterized as Long-COVID. This study aimed to assess the experience and awareness of Long-COVID clinical symptoms in Saudi Arabia.

METHODS: This cross-sectional study was conducted at the College of Medicine, Alfaisal University, Riyadh, Saudi Arabia during the period April 5, 2023 to August 30, 2023. An online questionnaire was created using Google Forms and distributed with a URL to students via email and WhatsApp. The questionnaire consisted of 17 questions classifying the respondent's responses. The survey consisted of three sections, addressing demographics, their experience with COVID-19 and whether they had Long-COVID symptoms. A total of 490 participants participated in the study survey. The Statistical Package for Social Sciences (SPSS) version 28 was used for data administration and analysis. P-values <0.05 were considered statistically significant.

RESULTS: Out of the participants, 53.9% had prior exposure to COVID-19. During acute infection, tiredness was the most common symptom in participants, observed in 84.5% of people. The other common symptoms which were reported among the participants included fever (75%), soreness of throat (65.5%), headache (65.2). Some symptoms were more dominant in males (such as acne) and some in females (hair loss). Regarding prolonged symptoms, 43.6% of females and 33.3% of males had experienced symptoms of Long-COVID. Tiredness was once again the most dominant symptom (16.7%). The other common prolonged symptoms of Long-COVID observed were loss of taste or smell (9.1%), body pain (7.6%), headache (7.2%), foggy memory (7.2%) and shortness of breath (6.4%). Lastly, awareness of Long COVID was lower than expected, with 51.5% of females and 55.1% of males unaware of the syndrome.

CONCLUSION: This study's findings show the effects Long COVID-19 has on the general population, which includes various symptoms affecting physical, mental and emotional needs. The findings also suggest potential gender differences in Long-COVID clinical symptoms, thus highlighting the need for further research with larger and more diverse samples.}, } @article {pmid40176592, year = {2025}, author = {Giorgianni, C and Cianci, V and Pitrone, C and Burrascano, G and Mondello, C and Gullì, N and Gualniera, P and Asmundo, A and Sapienza, D}, title = {Occurrence Of Long COVID In Healthcare Workers At A University Hospital And Challenges In Insurance And Compensation Evaluation.}, journal = {La Clinica terapeutica}, volume = {176}, number = {2}, pages = {213-218}, doi = {10.7417/CT.2025.5208}, pmid = {40176592}, issn = {1972-6007}, mesh = {Humans ; *COVID-19/epidemiology/economics/complications/diagnosis ; Hospitals, University ; *Health Personnel/statistics & numerical data ; Male ; Adult ; Female ; Middle Aged ; Italy/epidemiology ; Post-Acute COVID-19 Syndrome ; *Occupational Diseases/epidemiology/economics ; *Workers' Compensation ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developed in 2019, led to the outbreak of the COVID-19 pandemic state, which have significantly impacted on healthcare systems worldwide. During the pandemic state, in addition to all the problems related to high mortality and morbidity during the active phase of the disease, it had to deal with a condition known as "Long-COVID". Long-COVID includes both persistent symptomatic forms, where signs and symptoms last between 4 and 12 weeks, and post-COVID syndrome, where symptoms persist beyond 12 weeks. The evaluation system categorizes COVID-19 outcomes into four classes based on the degree of biological validity impairment: mild, moderate, moderate-severe, and severe. In the insurance field, this new "entity" led to difficulties related to damages compensation for infections developed in workplace, which has not completely been clarified nor today.

METHODS: The study was conducted on a sample of 3,127 health-care workers employed at the "G. Martino" University Hospital, in Messina. The percentage of individuals who contracted COVID-19 was analysed, evaluating how many were infected at workplace. Among those who contracted the virus at work, we further examined how many healthcare professionals were eligible for compensation under insurance frameworks related to Long- COVID.

RESULTS: The data analysis reveals that, out of the entire sample examined, 10 healthcare workers developed Long-COVID syndrome, with a severity classified as moderate (Biological Damage according to social insurance of healthcare workers: 1-15%). The lingering ef-fects included persistent asthenia, anosmia, stress-induced dyspnoea, outcomes of instrumentally documented pneumonia and myocarditis, as well as neuromuscular disorders. The collected data confirms that healthcare professionals had the highest percentage of COVID-19 infections (Fig. 1), with an infection rate of 23%, more than half of which occurred in the workplace.

DISCUSSION AND CONCLUSIONS: The definition of long-COVID is still quite complicated, as the ever-increasing number of symptoms that are attributable to this pathology, and the variability in the times of its onset, make its nosographic framework extremely difficult. In addition to the clinical-scientific difficulties arising from this condition, the impossibility of adequately classifying the pathology is associated with an equally complex management of the costs that the State must bear to restore the damage, as it usually happens in case of sequelae of infections contracted at workplace.}, } @article {pmid40175915, year = {2025}, author = {Rohde, J and Bundschuh, R and Kaußner, Y and Simmenroth, A}, title = {Lingering symptoms in non-hospitalized patients with COVID-19 - a prospective survey study of symptom expression and effects on mental health in Germany.}, journal = {BMC primary care}, volume = {26}, number = {1}, pages = {94}, pmid = {40175915}, issn = {2731-4553}, mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; Germany/epidemiology ; Female ; Male ; Middle Aged ; Prospective Studies ; Adult ; Aged ; *Mental Health ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Anxiety/epidemiology ; Depression/epidemiology ; Fatigue ; }, abstract = {BACKGROUND: The infection rates with SARS-CoV 2 virus, known since 2019, are currently significantly weakened in their dynamics. Nevertheless, COVID 19 is still a common disease, which in most cases is overcome quite well and can be treated by the general practitioner. Despite an initially uncomplicated disease progression, the long-term consequences can be considerable. Symptoms persisting over a period of more than 12 weeks after infection are summarized as Post-COVID (PC) syndrome. The aim of this study is to document the symptom expression in PC patients in the outpatient setting, with a major focus on limitations in daily life and consequences for mental health.

METHODS: This survey is part of a prospective European collaborative study with the German cohort having been slightly extended and evaluated separately. Data collection was performed by telephone interviews of adult SARS CoV 2 positive patients using standardized questionnaires (38 open and 6 closed questions). After an inclusion interview, follow-up interviews were conducted every 4 weeks over a period of 6 months. Participants were recruited in collaboration with the local health department (Wuerzburg, Germany).

RESULTS: Sixty participants were recruited in April and May 2021. After 12 weeks (PC cutoff), 48.3% still reported symptoms related to SARS-CoV-2 infection. The most commonly reported symptoms were fatigue/tiredness (33.3%), reduced concentration (26.7%), and shortness of breath (23.3%). One-quarter of respondents reported impaired functioning, with the most common daily limitations being sports (28.3%), work (25.0%), and social life (15.0%). At 6 months, 21.6% of respondents experienced anxiety and 11.6% reported depressive symptoms. Overall, 40.0% of respondents were concerned that their health would deteriorate again or not fully normalize because of COVID-19. Over two-thirds (70.0%) visited a physician during the course of the study because of COVID-19, 73.8% of whom visited their general practitioner.

CONCLUSION: PC in outpatient care appears to be a complex and multifaceted condition that not only presents with physical symptoms, but also has a significant impact on mental health and daily life. Although the complexity of the condition is not yet fully understood, our findings suggest that it presents long-term challenges, particularly in outpatient care. Further research, particularly in larger and more diverse cohorts, is needed to confirm these observations. Routine screening for psychosocial comorbidities could be a valuable approach to identify supportive interventions that may help to reduce the risk of chronification and/or somatization.}, } @article {pmid40175252, year = {2025}, author = {Tarasco, MC and Iacomino, N and Mantegazza, R and Cavalcante, P}, title = {COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons?.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2025.03.014}, pmid = {40175252}, issn = {1995-9133}, abstract = {The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus infection, has been associated with a substantial risk of autoimmune disease development or exacerbation. The postulated pathophysiological mechanisms linking COVID-19 with autoimmunity include reactivation of latent Epstein-Barr virus (EBV), whose dysregulated infection in the host can trigger or promote an autoimmune response. This review summarizes recent studies highlighting a potential immunopathogenetic link between SARS-CoV-2 infection and EBV reactivation, which could underlie autoimmunity onset or worsening, as well as immune-related long COVID manifestations in COVID-19 patients. We offer our perspective on the direction that research should take to disentangle the nature (whether causal or casual) of the "COVID-19-EBV-autoimmunity" liaisons. Further advances in this research area may be crucial for designing strategies to prevent or treat EBV reactivation-related autoimmune conditions in COVID-19 patients, or patients with inflammatory co-infectious diseases, at the same time promising to improve our knowledge on the viral contribution to autoimmune phenomena.}, } @article {pmid40171435, year = {2025}, author = {Murad, M and Atkin, SL and Wasif, P and Behzad, AA and Husain, AMJA and Leahy, R and d'Hellencourt, FL and Joury, J and Aziz, MA and Valluri, SR and Haridy, H and Spinardi, J and Kyaw, MH and Al-Qahtani, M}, title = {Burden of acute and long-term COVID-19: a nationwide study in Bahrain.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1539453}, pmid = {40171435}, issn = {2296-2565}, mesh = {Humans ; Bahrain/epidemiology ; *COVID-19/epidemiology/mortality ; Female ; Retrospective Studies ; Middle Aged ; Adult ; Male ; Aged ; Risk Factors ; *SARS-CoV-2 ; Incidence ; Adolescent ; Young Adult ; Post-Acute COVID-19 Syndrome ; Child ; Cost of Illness ; Aged, 80 and over ; Child, Preschool ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) may lead to long-term sequelae. This study aimed to understand the acute and post-acute burden of SARS-CoV-2 infection and to identify high-risk groups for post-COVID-19 conditions (PCC).

METHODS: A retrospective observational study of the Bahraini population was conducted between 1 May 2021 and 30 April 2023, utilizing the national administrative database. PCC cases were defined according to WHO guidelines. All COVID-19 cases were confirmed using real-time polymerase chain reaction (PCR).

RESULTS: Of 13,067 COVID-19 cases, 12,022 of them experienced acute COVID-19, and 1,045 of them developed PCC. Individuals with PCC tended to be older women with risk factors and instances of SARS-CoV-2 reinfection. The incidence rates per 100,000 individuals during the Alpha pandemic surge (2020), Delta pandemic surge (2021), and Omicron pandemic surge (2022) were 2.2, 137.2, and 222.5 for acute COVID-19, and 0.27, 10.5, and 19.3, respectively, for PCC cases. The death rates per 100,000 individuals during the Alpha, Delta, and Omicron pandemic surges were 3, 112, and 76, respectively, for acute COVID-19 and 1, 10, and 8, respectively, for PCC. The death rate was highest among those aged 65 and older during the Delta pandemic surge.

CONCLUSION: These findings suggest the need for a timely national vaccination program prior to new COVID-19 surges to prevent complications related to SARS-CoV-2 infection, particularly in the older adult and in non-older adult individuals with risk factors.}, } @article {pmid40171061, year = {2025}, author = {Kazal, LA and Huyck, KL and Kelly, B}, title = {Long COVID Response to Classical Chinese Medicine.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {24}, number = {2}, pages = {16-24}, pmid = {40171061}, issn = {1546-993X}, abstract = {BACKGROUND: Long COVID remains a significant burden for patients, clinicians, employers, and the U.S. healthcare system. Despite substantial resources and scientific studies directed at understanding and treating long COVID, its cause, and thus targeted treatment remains elusive. Conventional medicine focuses on symptom evaluation to rule out other etiologies. Intervention typically offers the patient current understanding and education and provides reassurance and context for their symptoms. Treatment is mostly supportive care directed at symptom management to improve quality of life, including occupational and physical therapy, breathing exercises, pulmonary rehabilitation, and mental health therapy. Classical Chinese Medicine (CCM) can help make sense of an individual's response to COVID-19 infection, as each pathophysiological change caused by COVID can be correlated with CCM principles, therefore a corresponding treatment approach is available.

METHODS: A case series of four representative patients with long COVID treated with CCM is presented. Symptom complex, CCM diagnoses and treatment, and response to treatment are provided for each case, and the rationale for the selected therapy approach is explained.

RESULTS: All four patients recovered fully from long COVID after treatment with CCM therapy. These cases are representative of 56 patients successfully treated thus far with CCM for long COVID.

CONCLUSION: There is no single treatment for long COVID in Western or Chinese medicine. Western medical treatment centers around reassurance and supportive care, whereas CCM treatment can be more directly targeted and individualized to underlying causes and increase the probability of recovery. These cases indicate the potential of CCM for treating long COVID. However, more research is needed to evaluate the effectiveness of this approach to long COVID recovery.}, } @article {pmid40171057, year = {2025}, author = {Baker, S}, title = {Dr. Jacob Teitelbaum Looks at Effectively Treating Long Covid.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {24}, number = {2}, pages = {30-32}, pmid = {40171057}, issn = {1546-993X}, } @article {pmid40170623, year = {2025}, author = {Iqbal, MM and Iqbal, A and Evans, RA}, title = {Long COVID update: respiratory sequelae and symptoms.}, journal = {Current opinion in supportive and palliative care}, volume = {}, number = {}, pages = {}, doi = {10.1097/SPC.0000000000000755}, pmid = {40170623}, issn = {1751-4266}, abstract = {PURPOSE OF REVIEW: Long COVID affects approximately 6% of the population after SARS-CoV-2 infection commonly involving persistent respiratory symptoms such as breathlessness and cough. This review provides an update on the latest evidence regarding post-COVID condition/Long COVID and respiratory sequelae, focusing on persistent symptoms, respiratory complications, and therapeutic approaches to date.

RECENT FINDINGS: Post-COVID interstitial lung abnormalities are estimated to persist in approximately 11% of patients hospitalized with acute COVID-19. However, breathlessness is common in adults (non-hospitalized) with Long COVID, suggesting aetiologies beyond pneumonitis. The risk of venous thromboembolic disease in Long COVID remains uncertain and trial results of anti-coagulation in Long COVID are awaited.

SUMMARY: Long COVID presents complex respiratory challenges, and careful assessment is crucial to differentiate Long COVID symptoms from exacerbations of pre-existing respiratory conditions. Current management includes a symptom-based multidisciplinary approach, with ongoing research into effective treatments including immune modulating agents.}, } @article {pmid40169752, year = {2025}, author = {Ponirakis, G and Al-Janahi, I and Elgassim, E and Al Obaidan, A and Gad, H and Petropoulos, IN and Khan, A and Zaghloul, HB and Ali, H and Siddique, MA and Mohamed, FFS and Ahmed, LHM and Dakroury, Y and El Shewehy, AMM and Al-Thani, SN and Ahmed, F and Hussein, R and Mahmoud, S and Salivon, I and Homssi, M and Hadid, NH and Ali, AM and Khan, S and Mahfoud, ZR and Zirie, MA and Bitirgen, G and Al-Ansari, Y and Alhatou, MI and Atkin, SL and Malik, RA}, title = {COVID-19 and neuropathy in type 2 diabetes.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11188}, pmid = {40169752}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/complications ; *Diabetes Mellitus, Type 2/complications ; Female ; Male ; Middle Aged ; *Diabetic Neuropathies/etiology ; Aged ; SARS-CoV-2/isolation & purification ; Risk Factors ; Blood Pressure ; Surveys and Questionnaires ; }, abstract = {This study investigated the risk factors for COVID-19 and its impact on diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Patients with T2D underwent assessments with the NICE post-COVID questionnaire, DN4 questionnaire, vibration perception threshold (VPT), and corneal confocal microscopy (CCM) before and 11.0 ± 8.9 months after developing COVID-19. Of 76 participants with T2D, 35 (46.1%) developed COVID-19, of whom 8 (22.9%) developed severe COVID-19 and 9 (25.7%) developed long-COVID. The development of COVID-19 was associated with lower systolic blood pressure (P < 0.05). The presence and severity of DPN were not associated with developing COVID-19, severe COVID-19, or long-COVID (P = 0.42-0.94). Women were eight times more likely to develop long-COVID (P < 0.05) and elevated body weight, LDL, and VPT were associated with the development of long-COVID (P < 0.05 - 0.01). The long-COVID group exhibited significant changes in triglycerides and LDL (P < 0.05 for both) and body weight (P < 0.01) at follow-up. Their impact on clinical and neuropathy measures was comparable in patients with and without COVID-19 (P = 0.08-0.99). There was a significant reduction in corneal nerve measures (P < 0.05-0.0001) in patients with and without COVID-19. A low systolic blood pressure, altered lipids, body weight, higher VPT, and gender may determine the impact of COVID-19 in patients with T2D, but there was no evidence of an impact of COVID-19 on the development or progression of DPN.}, } @article {pmid40169569, year = {2025}, author = {Zang, C and Guth, D and Bruno, AM and Xu, Z and Li, H and Ammar, N and Chew, R and Guthe, N and Hadley, E and Kaushal, R and Love, T and McGrath, BM and Patel, RC and Seibert, EC and Senathirajah, Y and Singh, SK and Wang, F and Weiner, MG and Wilkins, KJ and Zhang, Y and Metz, TD and Hill, E and Carton, TW and , and , and , }, title = {Long COVID after SARS-CoV-2 during pregnancy in the United States.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3005}, pmid = {40169569}, issn = {2041-1723}, mesh = {Humans ; Female ; Pregnancy ; *COVID-19/epidemiology/immunology/virology ; United States/epidemiology ; Adult ; *Pregnancy Complications, Infectious/epidemiology/virology ; Retrospective Studies ; *SARS-CoV-2 ; Adolescent ; Middle Aged ; Young Adult ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pregnancy alters immune responses and clinical manifestations of COVID-19, but its impact on Long COVID remains uncertain. This study investigated Long COVID risk in individuals with SARS-CoV-2 infection during pregnancy compared to reproductive-age females infected outside of pregnancy. A retrospective analysis of two U.S. databases, the National Patient-Centered Clinical Research Network (PCORnet) and the National COVID Cohort Collaborative (N3C), identified 29,975 pregnant individuals (aged 18-50) with SARS-CoV-2 infection in pregnancy from PCORnet and 42,176 from N3C between March 2020 and June 2023. At 180 days after infection, estimated Long COVID risks for those infected during pregnancy were 16.47 per 100 persons (95% CI, 16.00-16.95) in PCORnet using the PCORnet computational phenotype (CP) model and 4.37 per 100 persons (95% CI, 4.18-4.57) in N3C using the N3C CP model. Compared to matched non-pregnant individuals, the adjusted hazard ratios for Long COVID were 0.86 (95% CI, 0.83-0.90) in PCORnet and 0.70 (95% CI, 0.66-0.74) in N3C. The observed risk factors for Long COVID included Black race/ethnicity, advanced maternal age, first- and second-trimester infection, obesity, and comorbid conditions. While the findings suggest a high incidence of Long COVID among pregnant individuals, their risk was lower than that of matched non-pregnant females.}, } @article {pmid40169367, year = {2025}, author = {Khristichenko, M and Nechepurenko, Y and Grebennikov, D and Bocharov, G}, title = {Computation and analysis of stationary and periodic solutions of the COVID-19 infection dynamics model.}, journal = {Journal of bioinformatics and computational biology}, volume = {23}, number = {1}, pages = {2540001}, doi = {10.1142/S0219720025400013}, pmid = {40169367}, issn = {1757-6334}, mesh = {*COVID-19/immunology/virology ; Humans ; *SARS-CoV-2 ; *Viral Load ; Antibodies, Viral/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Models, Biological ; Computational Biology/methods ; Computer Simulation ; }, abstract = {In this work, we search for the conditions for the occurrence of long COVID using the recently developed COVID-19 disease dynamics model which is a system of delay differential equations. To do so, we search for stable stationary or periodic solutions of this model with low viral load that can be interpreted as long COVID using our recently developed technology for analysing time-delay systems. The results of the bifurcation and sensitivity analysis of the mathematical model of SARS-CoV-2 infection suggest the following biological conclusions concerning the mechanisms of pathogenesis of long COVID-19. First, the possibility of SARS-CoV-2 persistence requires a 3-time reduction of the virus production rate per infected cell, or 18-times increase of the antibody-mediated elimination rate of free viruses as compared to an acute infection baseline estimates. Second, the loss of kinetic coordination between virus-induced type I IFN, antibody, and cytotoxic T lymphocyte (CTL) responses can result in the development of mild severity long-lasting infection. Third, the low-level persistent SARS-CoV-2 infection is robust to up to 100-fold perturbations (increase) in viral load and most sensitive to parameters of the humoral immune response.}, } @article {pmid40168796, year = {2025}, author = {Zhang, L and Li, H and Shi, L and Geng, J and Zhang, H and Chen, H and Zhao, P and Xiao, Y and Lu, J and Li, Z and Pu, H and Hou, C and Li, C and Gao, C and Song, X and Bao, Z and Zhai, B and Guo, B and Yang, B and Lu, X and Yu, Q}, title = {Mechanism and Efficacy of Etanercept in Treating Autoimmune-like Manifestations of Coronavirus Disease 2019 in elderly individuals.}, journal = {Immunobiology}, volume = {230}, number = {3}, pages = {152898}, doi = {10.1016/j.imbio.2025.152898}, pmid = {40168796}, issn = {1878-3279}, abstract = {During the COVID-19 pandemic, extensive research focused on universal treatments, but few studies addressed treatment regimens for elderly patients. This study aimed to evaluate the effects of etanercept, a TNF inhibitor, in elderly individuals with COVID-19 through observational analysis of compassionate use cases. The results showed that after one month of etanercept treatment, clinical indicators such as C-reactive protein, D-dimer, and fibrinogen normalised, whereas the control group receiving conventional treatment did not fully recover. Single-cell sequencing was performed on seven patients treated with etanercept and two uninfected individuals. Based on our data and in conjunction with external data, a comprehensive characterization map involving 400,000 cells was created. Transcriptomic analysis revealed autoimmune-like manifestations in elderly patients, highlighting the importance of immunotherapy. Plasma cells, platelets, and B cells were the most treatment-sensitive cells. Analysis of five drug types, including antiviral, etanercept, glucocorticoids, tocilizumab, and others, showed that tocilizumab was associated with an increased thrombosis risk in elderly patients. Meanwhile, etanercept alleviated autoimmune-like manifestations by inhibiting platelet factor 4 and suppressing TNF-α. Molecular docking showed etanercept's strong affinity (-15.0 kcal/mol) for the spike protein of the SARS-CoV-2 Omicron variant, suggesting it may protect immune-compromised patients. Our findings support etanercept as a potential treatment for elderly COVID-19 patients with autoimmune-like manifestations.}, } @article {pmid40168377, year = {2025}, author = {Akbaba Bağcı, B and Satıcı, C}, title = {Factors associated with long COVID at a pandemic hospital in Turkey: a prospective observational study with 3-month follow-up.}, journal = {Journal of infection in developing countries}, volume = {19}, number = {3}, pages = {342-352}, doi = {10.3855/jidc.18998}, pmid = {40168377}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Female ; Male ; Turkey/epidemiology ; Middle Aged ; Prospective Studies ; Adult ; Follow-Up Studies ; *Anxiety/epidemiology ; SARS-CoV-2 ; Aged ; Sex Factors ; Severity of Illness Index ; Tertiary Care Centers/statistics & numerical data ; Hospitalization/statistics & numerical data ; }, abstract = {INTRODUCTION: The aim of this study was to evaluate the course of the coronavirus disease 2019 (COVID-19) symptoms and identify the prognostic factors in patients who continued to have symptoms for ≥ 3 months. The occurrence of symptoms was compared based on gender.

METHODOLOGY: This was a prospective cohort study performed at a tertiary chest hospital in Turkey. The clinical features of patients with COVID-19, health anxiety scores, and the course of symptoms at admission and follow-up were compared based on gender. The primary outcome was the distribution and rate of persistent symptoms at the third month; and the secondary outcomes were the number and distribution of symptoms by gender, and the relationship between symptoms and health anxiety.

RESULTS: A total of 110 patients (mean age of 45 years) were followed. Of these, 53 (48%) patients were females. Forty-seven (43%) patients, including 17 (32%) females, were hospitalized. The number of highly symptomatic patients with mild disease severity (level 2) was significantly higher among females than males (p = 0.008). Eighty-one (74%) patients followed had at least 1 symptom persisting at the end of the third month. During the 3-month follow-up, the total number of symptoms and health anxiety scale scores were significantly higher in females (p = 0.04 and p = 0.004, respectively), especially in females aged < 50 years (p = 0.005).

CONCLUSIONS: Thus, persistent symptoms remained at a high rate at 3 months post-COVID; and gender and neuro-psychiatric factors should be discussed in the etiology of long COVID.}, } @article {pmid40168375, year = {2025}, author = {Hussein, NR and Khalid, RC and Jamal, TB and Mahdi, SA and Mustafa, AS and Mohammed, BI and Shukri, MA and Naqid, IA and Ameen, RM}, title = {Prevalence of anti-SARS-CoV-2 IgG positivity and long COVID-19 in pediatric age group.}, journal = {Journal of infection in developing countries}, volume = {19}, number = {3}, pages = {335-341}, doi = {10.3855/jidc.19299}, pmid = {40168375}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/epidemiology/immunology ; Male ; Child ; Female ; *Immunoglobulin G/blood ; Cross-Sectional Studies ; Child, Preschool ; *SARS-CoV-2/immunology ; Prevalence ; *Antibodies, Viral/blood ; Iraq/epidemiology ; }, abstract = {INTRODUCTION: This study aimed to determine the prevalence and associated factors of coronavirus disease 2019 (COVID-19) and long COVID-19 in children in Duhok province and Zakho city in the Kurdistan region.

METHODOLOGY: The study was conducted as a cross-sectional study and included children aged 5-12 years in Duhok and Zakho, two major neighboring cities in the Bahdenan region of northern Iraq. A total of 330 participants were included and the study was conducted between October 2022 and April 2023. The children were tested for the presence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies. A questionnaire was used to collect demographic and personal data, and symptoms of each participant to determine the prevalence of long COVID-19.

RESULTS: Out of 330 participants, 302 (91.5%) were positive for IgG, and 156 (51.7%) of them were male. Only 4 participants (1.3%) had pneumonia, and 282 (93.4%) were asymptomatic. Fourteen out of 302 (4.6%) participants had long COVID-19. There were significant associations between long COVID-19 and history of previous COVID-19 episodes (p = 0.001), presence of pneumonia (p = 0.001), and family history of COVID-19 (p = 0.005).

CONCLUSIONS: There was a high prevalence of COVID-19 among children in Duhok province and Zakho city, and 4.6% of them experienced long COVID-19. Factors such as prior COVID-19, pneumonia, and family history of COVID-19 were associated with long COVID-19. Continued monitoring, education, vaccination, preventive measures, and supportive care are recommended to effectively address the impact of COVID-19 on the pediatric population.}, } @article {pmid40168258, year = {2025}, author = {Yoon, J and Kim, S and Kwon, CY and Kang, JW and Kim, TH and Kwon, S}, title = {Kyungok-go for fatigue in patients with long COVID: Double-blind, randomized, multicenter, pilot clinical study protocol.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319459}, doi = {10.1371/journal.pone.0319459}, pmid = {40168258}, issn = {1932-6203}, mesh = {Humans ; *Fatigue/drug therapy/etiology ; Pilot Projects ; *COVID-19/complications ; Double-Blind Method ; *Quality of Life ; Female ; Male ; Adult ; Middle Aged ; SARS-CoV-2/drug effects ; Treatment Outcome ; COVID-19 Drug Treatment ; Aged ; }, abstract = {The most common symptom reported by patients after recovery from coronavirus disease 2019 (COVID-19) is fatigue. However, robust clinical evidence supporting the effectiveness of treatments and interventions for fatigue in COVID-19 survivors is lacking. This pilot clinical trial aims to assess the safety and efficacy of Kyungok-go, a herbal preparation targeting fatigue, in patients after recovering from COVID-19. The study will include 100 participants with persistent fatigue for more than 12 weeks after COVID-19 recovery. They will be randomly allocated into two groups: the Kyungok-go group (n = 50) and the placebo group (n = 50). Kyungok-go or placebo will be administered twice daily for 12 weeks, and the participants will be assessed at 4-week intervals. The primary outcome will be the change in the Fatigue Severity Scale score. Secondary outcomes will include cognitive function, physical function, quality of life, depression, sleep quality, medication adherence, and feasibility. This study is the first attempt to investigate the safety and efficacy of Kyungok-go for relieving fatigue related to long COVID. The results are expected to contribute to the establishment of a knowledge base and reveal the potential of herbal medicine prescriptions for managing and recovering from the most common sequelae of COVID-19. Trial registration number: KCT0008789.}, } @article {pmid40167955, year = {2025}, author = {G, MH and Agni, MB and M, DGK}, title = {Long-term health consequences of COVID-19 in young adults: a focus on respiratory and cardiovascular endurance.}, journal = {Irish journal of medical science}, volume = {}, number = {}, pages = {}, pmid = {40167955}, issn = {1863-4362}, support = {2022-10653//Indian Council of Medical Research/ ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has significantly impacted health, extending beyond the acute phase of illness. Among young adults, "long COVID" has raised concerns regarding respiratory and cardiovascular endurance. This study evaluates pulmonary function test (PFT), distance travelled in the 6-min walk test (6MWT), and changes in SpO2 and respiratory rate before and after 6MWT in COVID-19 convalescent patients compared to healthy controls.

METHODS: This case-control study included 45 controls and 45 COVID-19 convalescent patients confirmed by RT-PCR. Data on PFT, distance travelled in 6MWT, SpO2, and respiratory rate were collected. The associations were analyzed using the Student t-test and ANOVA, with p < 0.05 considered significant.

RESULTS: Significant reductions were observed in FVC (p = 0.02), FEV1 (p = 0.007), FEF25% (p = 0.0001), FEF50% (p = 0.003), FEF25-75% (p = 0.02), and PEFR (p = 0.0001), with an increased lung age (p = 0.01) in COVID-19 convalescent patients compared to controls. No significant difference was observed in FEV1/FVC ratio, FEV3, FEV3/FVC ratio, or FEF75%. While percentage saturation of oxygen, respiratory rate, and distance travelled in 6MWT showed no significant differences between groups, respiratory rate (p = 0.0001) and pulse rate (p = 0.001) differed significantly before and after 6MWT.

CONCLUSIONS: COVID-19 convalescent patients exhibited significant declines in FVC, FEV1, FEF25%, FEF50%, and FEF25-75%, indicating potential restrictive or obstructive lung defects. Increased lung age also suggests long-term impacts of SARS-CoV-2 on respiratory performance.}, } @article {pmid40166659, year = {2025}, author = {Dun-Dery, F and Xie, J and Zemek, R and Winston, K and Burstein, B and Sabhaney, V and Emsley, J and Gravel, J and Kam, A and Mater, A and Beer, D and Porter, R and Freire, G and Poonai, N and Moffatt, A and Berthelot, S and Salvadori, MI and Reddy, D and Wright, B and Freedman, SB}, title = {Pediatric SARS-CoV-2 infection and development of anxiety and depression.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1524617}, pmid = {40166659}, issn = {2296-2360}, abstract = {OBJECTIVE: It remains unclear whether emerging mental health concerns in children infected with SARS-CoV-2 are a direct result of the infection or due to the indirect effects of the pandemic. Therefore, we sought to assess the frequency of new diagnoses of anxiety and/or depression among children diagnosed with and without SARS-CoV-2 infection who were tested in pediatric emergency departments.

METHODS: A prospective cohort study with 6- and 12-month follow-ups was conducted across 14 Canadian tertiary-care pediatric emergency departments of the Pediatric Emergency Research Canada (PERC) network. The study included children aged <18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. The primary outcome was the diagnosis of anxiety and/or depression reported during follow-up. The surveys incorporated a modified version of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Long-COVID Pediatric Questionnaire.

RESULTS: Among the participants who were eligible for 6- and 12-month follow-ups, 64.7% (268/414) of SARS-CoV-2-positive and 71.9% (743/1,033) of SARS-CoV-2-negative participants completed follow-up at these time points, respectively. The median age was 7.0 [inter-quartile range (IQR): 5.0-11.0] years, and 54.2% (548/1,011) were male. New diagnoses of anxiety and/or depression reported on either survey did not differ significantly between test-positive (4.1%, 11/268) and test-negative (2.8%; 21/743) participants [difference = 1.3% (95% CI: -1.3 to 4.2)]. There was a higher prevalence of new diagnoses of anxiety and/or depression among SARS-CoV-2-negative participants aged ≥12 years relative to those aged <12 years [8.7% (13/149) vs. 1.3% (8/594); difference = 7.4%; 95% CI of the difference = 3.0-12.5], but not among SARS-CoV-2-positive participants [4.4% (2/45) vs. 4.0% (9/223); difference = 0.4%; 95% CI of the difference = -5.6 to 9.4]. At 6 or 12 months, SARS-CoV-2-positive participants were more likely to experience confusion and/or lack of concentration, abdominal pain, and insomnia.

CONCLUSIONS: Although no association was found between SARS-CoV-2 infection and new diagnoses of anxiety and/or depression, SARS-CoV-2-positive participants were more likely to experience confusion/lack of concentration, abdominal pain, and insomnia. This finding, in the context of an increased prevalence of new diagnoses of anxiety and depression, underscores the impacts of societal changes on the mental health of children. Our finding that some non-specific symptoms were more frequently reported by SARS-CoV-2-positive participants emphasizes the need for further investigation of the underlying pathophysiologic mechanisms.}, } @article {pmid40165957, year = {2025}, author = {Saheb Sharif-Askari, F and Raber, J and Alzoubi, KH}, title = {Editorial: Long COVID and brain inflammation: unravelling mechanisms and potential therapies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1575669}, pmid = {40165957}, issn = {1664-3224}, } @article {pmid40162934, year = {2025}, author = {Yang, J and Tamberou, C and Arnee, E and Squara, PA and Boukhlal, A and Nguyen, JL and Volkman, HR and Fiévez, S and Lepoutre-Bourguet, M and Ren, J and Ben Romdhane, H and Crépey, P and Robineau, O}, title = {All-cause healthcare resource utilization and costs among community-managed adults with long-COVID in France, 2020-2023.}, journal = {Journal of medical economics}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/13696998.2025.2485626}, pmid = {40162934}, issn = {1941-837X}, abstract = {BACKGROUND: The clinical and economic burden of long-COVID is poorly understood. We aim to assess all-cause healthcare resource utilization (HCRU) and costs in the primary care setting among adults with long-COVID in France.

METHODS: A retrospective cohort study using the electronic records of confirmed and/or probable COVID-19 patients from The Health Improvement Network (THIN) data between March 2020-December 2022 was conducted. Long-COVID was identified per World Health Organization (WHO) as suggestive symptoms present ≥3 months following acute SARS-CoV-2 infection. Patients' characteristics, HCRU, direct healthcare and indirect costs (National Health Insurance-based prices) were summarized. Costs between patients with previous SARS-CoV-2 infection who developed long-COVID, patients with previous SARS-CoV-2 infection who did not develop long-COVID (COVID only), and contemporaneous controls without SARS-CoV-2 infection were compared (Non-COVID).

RESULTS: Long COVID developed among 30,122 (11.6%) adults; mean (SD) age was 50 (17) years, 63.6% were female and 27.5% had a Charlson Comorbidity Index score >2. During the post-infection follow-up (mean = 13 months), 97.3% of patients had general practitioner consultations (GP) and 62.4% had nursing care. Costs were highest during the first post-diagnosis year with per patient per year costs of €2,443 (total cost of €52 million), including costs for GP (€208) and specialist (€170), outpatient procedures (€413), retail pharmacy use (€595), biological testing (€147), and medical device usage (€172). Patients with long COVID had additional costs of €163 and €176 when comparing to patients in the COVID only and Non-COVID cohorts, respectively.

LIMITATIONS: Since the THIN database is generated from GP EHRs, there is the possibility of measurement/documentation errors and missing values which could compromise the validity and accuracy of certain results.

CONCLUSION: Long COVID was associated with non-negligible HCRU, direct and indirect costs to the French healthcare system. These findings reinforce the importance of optimizing long-term resource allocation for patients infected with SARS-CoV-2.}, } @article {pmid40162470, year = {2024}, author = {Fotovat, L and Wang, K and Chiappelli, F}, title = {Integrating MICRORNA941 and T cell subset research into public health strategies for managing inflammaging in elderly and immune-compromised patients.}, journal = {Bioinformation}, volume = {20}, number = {11}, pages = {1529-1531}, pmid = {40162470}, issn = {0973-2063}, abstract = {As of 2022, the Centers for Disease Control and Prevention (CDC) reported that the average life expectancy for both sexes in the United States is 77.5 years. While new advances in health have increased life expectancy, aging comes with complications that impact the development of diseases like cancer, senile dementia (non-Alzheimer), diabetes and Parkinson's. Through aging, the body's immune system declines, a process recognized as immunosenescence and which contributes to inflammaging, a state of chronic, though non-productive, inflammation that progresses with advancing age in the absence of overt infection and that contributes to the onset and progression of a spectrum of age-related pathologies. MicroRNAs are small forms of RNA that control gene expression by binding to messenger RNA (mRNA) in the cell cytoplasm. In particular, microRNA-941 (miR-941) has been found to play a critical role in the regulation of differentiation of cell populations, certain T cell subsets responsible for maintaining efficient immune surveillance in normal subjects, immune compromised individuals as well as the elderly. We propose that concerted research designed to define and characterize interventions targeting the regulatory effects of miRNA-941 specifically on T-cell subsets will benefit treatment of infectious (e.g., CoViD-19, H5N1 infection) and chronic illnesses (e.g., diabetes II, diabetes III, Long Covid [i.e., Post-Acute Covid-19 Syndrome, PACS], autoimmune disease), which are most common among the aging and the immune compromised population. It is possible and even probable that active research in this specific area will proffer new horizons for finding cures, aid in disease management and improved accessibility and affordability of public health services.}, } @article {pmid40162374, year = {2025}, author = {Jafarzadeh, S and Eslami, S}, title = {The long-term Effects of the Coronavirus Disease (COVID-19) on Auditory Thresholds: A Case-Control Study.}, journal = {Iranian journal of otorhinolaryngology}, volume = {37}, number = {2}, pages = {85-86}, pmid = {40162374}, issn = {2251-7251}, abstract = {INTRODUCTION: The available evidence about hearing loss in Coronavirus disease (COVID-19) patients mostly show sensorineural hearing loss, and the long-term effects of COVID-19 on auditory thresholds are unknown. This study aimed to compare the auditory threshold results in COVID-19 patients (several months after infection) with a control group.

MATERIALS AND METHODS: The clinical diagnosis of COVID-19 was confirmed with positive polymerase chain reaction findings and radiology images. Hearing evaluation was performed with an audiometry test and a calibrated audiometer in a sound-treated room. The results of 177 patients were compared with those of the 589 matched control group. In both groups, subjects over 50 years old or with any history of ear disease were excluded from the study.

RESULTS: The time interval between infection with COVID-19 and hearing tests was 170.51±98.38 days. There was no significant difference between the auditory thresholds in different frequencies in both groups. Also, no significant difference was observed between the auditory thresholds of the two groups in the first, second, and third trimesters after being infected.

CONCLUSION: This study did not show the long-term effects of COVID-19 on auditory thresholds, and the findings do not support hearing loss as a long-term COVID symptom.}, } @article {pmid40162023, year = {2025}, author = {Elia, S and De Vecchi, S and D'Amario, D and Patti, G}, title = {A case report of long COVID-19 and chronic active myocarditis.}, journal = {European heart journal. Case reports}, volume = {9}, number = {4}, pages = {ytaf100}, pmid = {40162023}, issn = {2514-2119}, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as 'Long COVID-19', are progressively emerging in the population. While it was clear from the pandemic outbreak that pre-existing cardiac conditions were exacerbated by the infection even after its resolution, little is known about the rare cases of de novo heart failure onset, whose mechanisms are still not fully understood.

CASE SUMMARY: A 74-year-old man was admitted to the emergency department with SARS-CoV-2 bilateral interstitial pneumonia at the computed tomography scan. A few months after, he developed acute myocarditis that slowly led to progressive myocardial fibrosis, systolic dysfunction, and a pro-arrhythmic state. Furthermore, these manifestations were associated with growing 'mental dullness' and chronic psychophysical asthenia. The patient underwent two cardiac MRI over 3 years witnessing the worsening of cardiac involvement and started full pharmacological therapy for heart failure. We report here the initial presentation, medical care, and clinical course of this patient.

DISCUSSION: In SARS-CoV-2 patients, long COVID-19-related myocarditis is one of the more severe complications. A thorough multimodal evaluation of these patients should be conducted, as presentation symptoms can appear subtle or misleading. Early identification of a chronic process of myocardial damage is crucial to implement early therapeutic strategies and prevent the potential worsening of heart failure.}, } @article {pmid40161283, year = {2025}, author = {Borges, SAM and Roncete, GP and Amendola, FC and Zanetti, MV and Miguel, EC and Filho, GB and Forlenza, OV and Damiano, RF and , }, title = {Exploring the Relationship Between Lifestyle and Post-COVID Psychiatric Symptoms: Findings from a Brazilian Cohort.}, journal = {American journal of lifestyle medicine}, volume = {}, number = {}, pages = {15598276251328022}, pmid = {40161283}, issn = {1559-8284}, abstract = {Understanding how lifestyle factors impact psychiatric well-being is essential for supporting recovery in COVID-19 survivors, yet their influence on long-term outcomes remains underexplored. This cross-sectional study evaluates associations between depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), suicidal ideation (SI), and syndromic common mental disorder (CMD) with lifestyle factors in 730 moderate to severe COVID-19 survivors. Lifestyle factors included physical activity, alcohol and substance use and during COVID-19 infection, and dietary intake, with assessments conducted 6 to 11 months post-hospitalization. Multiple logistic regression was employed for each of the five dependent variables. Of the participants, 51.9% were male, with a mean age of 55. Previous COVID-19 sedative use and the severity of alcohol use were correlated with increased depression (sedative, OR = 2.43, P = .011; alcohol OR = 1.09, P = .017), GAD (sedative, OR = 2.13, P = .007; alcohol OR = 1.08, P = .009), PTSD (sedative, OR = 2.10, P = .008; alcohol OR = 1.08, P = .004), and sedative for CMD (OR = 1.97, P = .005). Opioid use was linked to increased GAD (OR = 2.23, P = .042), and "fruits and vegetables" consumption 2-3 times/week was associated with lower odds for depression (OR = 0.19, P = .021). No lifestyle behaviors were found to be associated with suicidal ideation. These results underscore the importance of lifestyle-specific behaviors in mitigating psychiatric symptoms during the extended recovery period from COVID-19. This is particularly pertinent with respect to minimizing the consumption of sedatives and alcohol in the context of depression, GAD, and PTSD, as well as the use of opioids for GAD and the increased intake of fruits and vegetables to depression. These findings may have substantial implications for the formulation of lifestyle strategies aimed at the prevention of mental health disorders subsequent to severe acute viral infections.}, } @article {pmid40157534, year = {2025}, author = {Jeong, H and Kim, SH and Kim, J and Jeon, D and Uhm, C and Oh, H and Cho, K and Park, IH and Oh, J and Kim, JJ and Jeong, SH and Park, JH and Park, JW and Yun, JW and Seo, JY and Shin, JS and Goldenring, JR and Seong, JK and Nam, KT}, title = {Post-COVID-19 effects on chronic gastritis and gastric cellular and molecular characteristics in male mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101511}, doi = {10.1016/j.jcmgh.2025.101511}, pmid = {40157534}, issn = {2352-345X}, abstract = {BACKGROUNDS & AIMS: Since the Omicron variant emerged as a major SARS-CoV-2 variant, COVID-19-associated mortality has decreased remarkably. Nevertheless, patients with a history of SARS-CoV-2 infection have been suffering from an aftereffect commonly known as 'long COVID', affecting diverse organs. However, the effect of SARS-CoV-2 on gastric cells and disease progression was not previously known. We aimed to investigate whether SARS-CoV-2 infection affects stomach cells and if post-COVID-19 conditions can lead to severe gastric disease.

METHODS: Stomach specimens obtained from male K18-hACE2 mice 7 days after SARS-CoV-2 infection were subjected to a transcriptomic analysis for molecular profiling. To investigate the putative role of SARS-CoV-2 in gastric carcinogenesis, K18-hACE2 mice affected by nonlethal COVID-19 were also inoculated with Helicobacter pylori SS1.

RESULTS: Despite the lack of viral dissemination and pathological traits in the stomach, SARS-CoV-2 infection caused dramatic changes to the molecular profile and some immune subsets in this organ. Notably, the gene sets related to metaplasia and gastric cancer were significantly enriched after viral infection. As a result, chronic inflammatory responses and preneoplastic transitions were promoted in these mice.

CONCLUSION: SARS-CoV-2 infection indirectly leads to profound and post-acute COVID-19 alterations in the stomach at the cellular and molecular levels, resulting in adverse outcomes following co-infection with SARS-CoV-2 and H. pylori. Our results show that two prevalent pathogens of humans elicit a negative synergistic effect and provide evidence of the risk of severe chronic gastritis in the post-COVID-19 era.}, } @article {pmid40156968, year = {2025}, author = {Perrot, JC and Segura, M and Flotats, G and Closa, C and Gich, I and Garcia, C and Alba, A and Nadal, MJ and Pintor, A and Terra, J and Ramirez, E and Beranuy, M and Bascuñana, H and Plaza, V and Güell-Rous, MR}, title = {Long COVID-19: Impact of a personalized rehabilitation program.}, journal = {Rehabilitacion}, volume = {59}, number = {2}, pages = {100903}, doi = {10.1016/j.rh.2025.100903}, pmid = {40156968}, issn = {1578-3278}, abstract = {INTRODUCTION: Several guidelines have proposed specific rehabilitation programs to treat symptoms/sequelae in patients with post-acute COVID syndrome (PACS). Only a few studies show that rehabilitation reduce disability after COVID-19.

OBJECTIVE: To describe the response to a personalized rehabilitation program in terms of exercise tolerance, muscle function, dyspnea, quality of life, and frailty state in a cohort of patients with PACS.

METHODS: Observational prospective cohort study of community-dwelling patients. The rehabilitation program included three modalities (outpatient, home-based, and self-administered), optionally supplemented with respiratory muscle training.

STUDY VARIABLES: 6-minute walking distance (6MWD), inspiratory muscle strength (PImax), dyspnea, muscle strength (estimated with the Medical Research Council scale and handgrip), health-related quality of life (HRQoL), and frailty estimated with the Short Physical Performance Battery (SPPB) and at 3- and 6-months following baseline.

RESULTS: Of 178 patients with PACS, 101 (56.7%) were enrolled in a rehabilitation program: 41.6% home-based, 27.7% outpatient, and 24.8% self-administered. Inspiratory muscle training (IMT) was provided to 56 patients, with 50 included in the rehabilitation program and 6 (5.9%) receiving IMT alone. Significant improvements were observed at 3 months in mMRC strength (p=0.001), SPPB (p<0.0001), handgrip strength (p=0.017), mMRC dyspnea, PImax (p<0.0001), and 6-MWD (p=0.008). Improvements persisted at 6 months for mMRC strength (p=0.048), SPPB (p=0.002), PImax (p<0.0001), and 6MWD (p=0.048). HRQoL mental and physical component scores improved only at 3 months.

CONCLUSIONS: Personalized rehabilitation for patients with PACS improved muscle parameters, dyspnoea, and exercise capacity, but not HRQoL, up to 6 months. Improvements in respiratory muscle strength were associated with reductions in dyspnoea and increased exercise capacity.}, } @article {pmid40155409, year = {2025}, author = {Guillén-Teruel, A and Mellina-Andreu, JL and Reina, G and González-Billalabeitia, E and Rodriguez-Iborra, R and Palma, J and Botía, JA and Cisterna-García, A}, title = {Identifying risk factors and predicting long COVID in a Spanish cohort.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {10758}, pmid = {40155409}, issn = {2045-2322}, support = {21259/FPI/19//Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia/ ; 22308/FPI/23//Fundación Séneca-Agencia de Ciencia y Tecnología de la Región de Murcia/ ; ID2022-136306OB-I00//Spanish Council of Science and Innovation/ ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Spain/epidemiology ; Female ; Male ; Risk Factors ; Middle Aged ; Aged ; Adult ; *SARS-CoV-2/isolation & purification ; *Comorbidity ; COVID-19 Vaccines/administration & dosage ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; Vaccination ; Cohort Studies ; Young Adult ; }, abstract = {Many studies have investigated symptoms, comorbidities, demographic factors, and vaccine effects in relation to long COVID (LC-19) across global populations. However, a number of these studies have shortcomings, such as inadequate LC-19 categorisation, lack of sex disaggregation, or a narrow focus on certain risk factors like symptoms or comorbidities alone. We address these gaps by investigating the demographic factors, comorbidities, and symptoms present during the acute phase of primary COVID-19 infection among patients with LC-19 and comparing them to typical non-Long COVID-19 patients. Additionally, we assess the impact of COVID-19 vaccination on these patients. Drawing on data from the Regional Health System of the Region of Murcia in southeastern Spain, our analysis includes comprehensive information from clinical and hospitalisation records, symptoms, and vaccination details of over 675126 patients across 10 hospitals. We calculated age and sex-adjusted odds ratios (AOR) to identify protective and risk factors for LC-19. Our findings reveal distinct symptomatology, comorbidity patterns, and demographic characteristics among patients with LC-19 versus those with typical non-Long COVID-19. Factors such as age, female sex (AOR = 1.39, adjusted p < 0.001), and symptoms like chest pain (AOR > 1.55, adjusted p < 0.001) or hyposmia (AOR > 1.5, adjusted p < 0.001) significantly increase the risk of developing LC-19. However, vaccination demonstrates a strong protective effect, with vaccinated individuals having a markedly lower risk (AOR = 0.10, adjusted p < 0.001), highlighting the importance of vaccination in reducing LC-19 susceptibility. Interestingly, symptoms and comorbidities show no significant differences when disaggregated by type of LC-19 patient. Vaccination before infection is the most important factor and notably decreases the likelihood of long COVID. Particularly, mRNA vaccines offer more protection against developing LC-19 than viral vector-based vaccines (AOR = 0.48). Additionally, we have developed a model to predict LC-19 that incorporates all studied risk factors, achieving a balanced accuracy of 73% and ROC-AUC of 0.80. This model is available as a free online LC-19 calculator, accessible at (LC-19 Calculator).}, } @article {pmid40154983, year = {2025}, author = {Craig, P and Campbell, M and Deidda, M and Dundas, R and Green, J and Katikireddi, SV and Lewsey, J and Ogilvie, D and de Vocht, F and White, M}, title = {Using natural experiments to evaluate population health and health system interventions: new framework for producers and users of evidence.}, journal = {BMJ (Clinical research ed.)}, volume = {388}, number = {}, pages = {e080505}, pmid = {40154983}, issn = {1756-1833}, abstract = {Natural experiments are widely used to evaluate the impacts on health of changes in policies, infrastructure, and services. The UK Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) have published a new framework for conducting and using evidence from natural experimental evaluations. The framework defines key concepts and describes recent advances in designing and planning evaluations of natural experiments, including the relevance of a systems perspective, mixed methods, and stakeholder involvement. It provides an overview of the strengths, weaknesses, applicability, and limitations of the range of methods now available, and makes good practice recommendations for researchers, funders, publishers, and users of evidence.}, } @article {pmid40152069, year = {2025}, author = {Chen, YH and Jan, JS and Yang, CH and Yen, TL and Linh, TTD and Annavajjula, S and Satapathy, MK and Tsao, SY and Hsieh, CY}, title = {Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {3}, pages = {e70348}, pmid = {40152069}, issn = {1755-5949}, support = {R113-020//Ditmanson Medical Foundation Chia-Yi Christian Hospital/ ; CGH-A10610//Cathay General Hospital/ ; }, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/therapy ; SARS-CoV-2 ; Animals ; Neuroinflammatory Diseases ; }, abstract = {BACKGROUND: The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.

METHODS: This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.

RESULTS: Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.

CONCLUSION: By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.}, } @article {pmid40151635, year = {2025}, author = {Almalag, HM and Altuwaijri, N and Alnaim, LS and Alassiri, D and Alsolaimi, G and Aldakhil, S and Aloola, NA and Alsabhan, JF and Bawazeer, GA and Juffali, LA and Alkofide, H and Alfaraj, R and Alkhudair, N and Aljadeed, R and Aljadeed, R}, title = {Prevalence and characteristics of long COVID among COVID-19 survivors in Saudi Arabia: A cross-sectional study.}, journal = {IJID regions}, volume = {15}, number = {}, pages = {100616}, pmid = {40151635}, issn = {2772-7076}, abstract = {OBJECTIVES: This study explores the prevalence, risk factors, and impact of long COVID among COVID-19 survivors in Saudi Arabia.

METHODS: A cross-sectional study involving 486 COVID-19 survivors was conducted. Participants were confirmed via polymerase chain reaction testing and enrolled from November 2020 to December 2020.

RESULTS: The study found a high prevalence of long COVID symptoms, with 61% of participants reporting persistent symptoms. The prevalence was similar across demographic factors: 43% were aged 18-30 years, 71% were female, and 30% had comorbidities. The most common symptoms included fatigue (56%), breathlessness (47%), loss of smell (44%), and muscle aches (40%), alongside digestive issues, chest pain, headaches, tachycardia, joint pain, and skin problems.

CONCLUSIONS: This study underscores the significance of understanding long COVID's impact on individuals' health and quality of life. It highlights the necessity for further research to guide health care strategies and support COVID-19 survivors in Saudi Arabia.}, } @article {pmid40149556, year = {2025}, author = {Cheng, Y and Zhao, L and Yu, H and Lin, J and Li, M and Zhang, H and Zhu, H and Cheng, H and Huang, Q and Liu, Y and Wang, T and Ling, S}, title = {Insights into the Correlation and Immune Crosstalk Between COVID-19 and Sjögren's Syndrome Keratoconjunctivitis Sicca via Weighted Gene Coexpression Network Analysis and Machine Learning.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149556}, issn = {2227-9059}, support = {2021GH08//Guangzhou Huangpu International Science and Technology Collaboration Project/ ; 2024A03J0278//Guangzhou Science and Technology Planning Project/ ; 2023A1515110232//Guangdong Basic and Applied Basic Research Foundation/ ; 2023//the Open Research Funds of the State Key Laboratory of Ophthalmology/ ; }, abstract = {Background: Although autoimmune complications of COVID-19 have aroused concerns, there is no consensus on its ocular complications. Sjögren's syndrome is an autoimmune disease accompanied by the ocular abnormality keratoconjunctivitis sicca (SS-KCS), which may be influenced by COVID-19. Thereby, we explored the possible interaction between COVID-19 and SS-KCS, and we aimed to elucidate the potential correlated mechanism. Methods: Differentially expressed genes (DEGs) in COVID-19 and SS-KCS transcriptome data obtained from the gene expression omnibus database were identified, and COVID-19-related genes were screened using weighted gene coexpression network analysis. Common genes were verified using four machine-learning diagnostic predictors. The clinical relationship between the two common hub genes of COVID-19 was analyzed. Finally, the immune cell types infiltrating the microenvironment in the COVID-19 dataset were analyzed using CIBERSORT, and the interrelation between key genes and differentially infiltrating immune cells was verified via Pearson correlation. Results: Ten potential primary hub mRNAs were screened by intersecting the COVID-19 DEGs, SS-KCS DEGs, and WGCNA genes. After a multifaceted evaluation using four mainstream machine-learning diagnostic predictors, the most accurate and sensitive random forest model identified CR1 and TAP2 as the common hub genes of COVID-19 and SS-KCS. Together with the clinical information on COVID-19, the expression of CR1 and TAP2 was significantly correlated with the status and severity of COVID-19. CR1 and TAP2 were significantly positively correlated with M0 and M2 macrophages, neutrophils, and CD4+ memory resting T cells and negatively correlated with activated NK cells, monocytes, and CD8+ T cells. Conclusions: We validated the hub genes associated with both COVID-19 and SS-KCS, and we investigated the immune mechanisms underlying their interaction, which may help in the early prediction, identification, diagnosis, and management of SARS-CoV-2 infection-related SS-KCS syndrome or many other immune-related complications in the long COVID period.}, } @article {pmid38700469, year = {2024}, author = {Berbrier, DE and Adler, TE and Leone, CA and Paidas, MJ and Stachenfeld, NS and Usselman, CW}, title = {Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {327}, number = {1}, pages = {H140-H154}, pmid = {38700469}, issn = {1522-1539}, support = {//American Heart Association (AHA)/ ; //FRQ | Fonds de Recherche du Québec - Santé (FRQS)/ ; R01 HL135089/HL/NHLBI NIH HHS/United States ; R01 HL161000/HL/NHLBI NIH HHS/United States ; R21 HD107609/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Female ; *Pre-Eclampsia/physiopathology/diagnosis ; Pregnancy ; Adult ; *Blood Pressure ; *Stress, Psychological/physiopathology ; *Hand Strength ; *Apnea/physiopathology ; *Sympathetic Nervous System/physiopathology ; Exercise ; Muscle, Skeletal/innervation/physiopathology ; Case-Control Studies ; }, abstract = {Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness with acute stimuli between previously preeclamptic (PPE) women (34 ± 5 yr old, 13 ± 6 mo postpartum) and women following healthy pregnancies (Ctrl; 29 ± 3 yr old, 15 ± 4 mo postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n = 12, Ctrl: n = 12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n = 6, Ctrl: n = 8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than Ctrl (main effects of group all P < 0.05). Peak changes in SBP were stressor specific: peak increases in SBP were not different between PPE and Ctrl during apnea (8 ± 6 vs. 6 ± 5 mmHg, P = 0.32) or mental stress (9 ± 5 vs. 4 ± 7 mmHg, P = 0.06). However, peak exercise-induced increases in SBP were greater in PPE than Ctrl (11 ± 5 vs. 7 ± 7 mmHg, P = 0.04). MSNA was higher in PPE than Ctrl across all protocols (main effects of group all P < 0.05), and increases in peak MSNA were greater in PPE than Ctrl during apnea (44 ± 6 vs. 27 ± 14 burst/100 hb, P = 0.04) and exercise (25 ± 8 vs. 13 ± 11 burst/100 hb, P = 0.01) but not different between groups during mental stress (2 ± 3 vs. 0 ± 5 burst/100 hb, P = 0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.NEW & NOTEWORTHY Women with recent histories of preeclampsia demonstrated higher systolic blood pressures across sympathoexcitatory stressors relative to controls. Peak systolic blood pressure reactivity was exacerbated in previously preeclamptic women during small muscle-mass exercises, although not during apneic or mental stress stimuli. These findings underscore the importance of assessing blood pressure control during a variety of experimental conditions in previously preeclamptic women to elucidate mechanisms that may contribute to their elevated cardiovascular disease risk.}, } @article {pmid40149333, year = {2025}, author = {Lasagna, A and Gambini, G and Klersy, C and Figini, S and Marino, S and Sacchi, P and Pedrazzoli, P}, title = {Real-World Experience with the Available Outpatient COVID-19 THErapies in Patients with canceR (CO.THER).}, journal = {Cancers}, volume = {17}, number = {6}, pages = {}, doi = {10.3390/cancers17060999}, pmid = {40149333}, issn = {2072-6694}, support = {grant no 08067620//Fondazione IRCCS Policlinico San Matteo Pavia/ ; }, abstract = {BACKGROUND/OBJECTIVES: Cancer represents an important risk factor for acquiring severe acute respiratory syndrome by Coronavirus-2 (SARS-CoV-2) and subsequent hospitalization. The utility of early antiviral therapies, including their protective effect on long COVID outcomes, in cancer patients has not yet been clearly demonstrated. We conducted the CO.THER study (COVID-19 THErapies in patients with canceR) to address this knowledge gap.

METHODS: We designed an ambispective single-center cohort study. We collected clinical and oncological data from the hospital's electronic patient records at the start of COVID-19 therapy (T0), seven days after T0 (T1), two weeks after T0 (T2), one month after T0 (T3), three months after T0 (T4), six months after T0 (T5), and twelve months after T0 (T6). The primary endpoint of this ambispective single-center cohort study was the rate of hospitalization for COVID-19 disease within 14 days in cancer patients using anti-SARS-CoV-2 early therapies. The proportion of hospitalizations within 14 days (primary endpoint) was computed together with its exact binomial 95% confidence interval (95%CI).

RESULTS: 131 patients' records (53M [40.5%], 78F, [59.5%]; median age 62.45, interquartile range [IQR] 56-71) were enrolled. As shown by the Kaplan-Meier hospitalization-free estimate, only three patients (2.1%) were hospitalized for a COVID-19 related cause within 14 days of starting early treatment (95%CI 0.5-6.6%). The cumulative survival probability beyond 12 months in hospitalization-free patients was 98% (95%CI 93-99%). Twelve patients (9.2%) reported another COVID-19 infection during the follow-up and they were all retreated with Nirmatrelvir-Ritonavir. The cumulative reinfection-free survival was 90% at 12 months (95%CI 83-95%). Further, 15 patients of the 123 evaluable at 3 months (median age 51 years, IQR 40-68) reported long COVID symptoms (12.2%, 95%CI 7.0-19.3%).

CONCLUSIONS: Our data demonstrate a low rate of hospitalization and reassuring data on safety in this cohort of high-risk subjects.}, } @article {pmid40146983, year = {2025}, author = {Mathew, J and Pagliaro, JA and Elumalai, S and Wash, LK and Ly, K and Leibowitz, AJ and Vimalananda, VG}, title = {Developing a Multisensor-Based Machine Learning Technology (Aidar Decompensation Index) for Real-Time Automated Detection of Post-COVID-19 Condition: Protocol for an Observational Study.}, journal = {JMIR research protocols}, volume = {14}, number = {}, pages = {e54993}, doi = {10.2196/54993}, pmid = {40146983}, issn = {1929-0748}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; *Machine Learning ; Male ; Female ; Post-Acute COVID-19 Syndrome ; Adult ; Middle Aged ; United States/epidemiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID-19 condition is emerging as a new epidemic, characterized by the persistence of COVID-19 symptoms beyond 3 months, and is anticipated to substantially alter the lives of millions of people globally. Patients with severe episodes of COVID-19 are significantly more likely to be hospitalized in the following months. The pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiovascular and pulmonary diseases, which are common among those at risk of severe disease.

OBJECTIVE: This study aims to use a single, integrated device-MouthLab, which measures 10 vital health parameters in 60 seconds-and a cloud-based proprietary analytics engine to develop and validate the Aidar Decompensation Index (AIDI), to predict decompensation in health among patients who previously had severe COVID-19.

METHODS: Overall, 200 participants will be enrolled. Inclusion criteria are patients in the US Department of Veterans Affairs health care system; "severe" COVID-19 infection during the acute phase, defined as requiring hospitalization, within 3-6 months before enrollment; aged ≥18 years; and having 1 of 6 prespecified chronic conditions. All participants will be instructed to use the MouthLab device to capture daily physiological data and complete monthly symptom surveys. Structured data collection tables will be developed to extract the clinical characteristics of those who experience decompensation events (DEs). The performance of the AIDI will depend on the magnitude of difference in physiological signals between those experiencing DEs and those who do not, as well as the time until a DE (ie, the closer to the event, the easier the prediction). Information about demographics, symptoms (Medical Research Council Dyspnea Scale and Post-COVID-19 Functional Status Scale), comorbidities, and other clinical characteristics will be tagged and added to the biomarker data. The resultant predicted probability of decompensation will be translated into the AIDI, where there will be a linear relationship between the risk score and the AIDI. To improve prediction accuracy, data may be stratified based on biological sex, race, ethnicity, or underlying clinical characteristics into subgroups to determine if there are differences in performance and detection lead times. Using appropriate algorithmic techniques, the study expects the model to have a sensitivity of >80% and a positive predicted value of >70%.

RESULTS: Recruitment began in January 2023, and at the time of manuscript submission, 204 patients have been enrolled. Publication of the complete results and data from the study is expected in 2025.

CONCLUSIONS: The focus on identifying predictor variables using a combination of biosensor-derived physiological features should enable the capture of heterogeneous characteristics of complications related to post-COVID-19 condition across diverse populations.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05220306; https://clinicaltrials.gov/study/NCT05220306.}, } @article {pmid40146692, year = {2025}, author = {Santos, CVBD and Coelho, LE and Goedert, GT and Luz, PM and Werneck, GL and Villela, DAM and Struchiner, CJ}, title = {Disability-adjusted life years associated with COVID-19 in Brazil, 2020.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0319941}, pmid = {40146692}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/mortality ; Brazil/epidemiology ; Male ; Female ; Adult ; Middle Aged ; *Disability-Adjusted Life Years ; SARS-CoV-2/isolation & purification ; Aged ; Hospitalization/statistics & numerical data ; Adolescent ; Young Adult ; Child ; Cost of Illness ; Child, Preschool ; Infant ; }, abstract = {BACKGROUND: We quantified the national- and state-level burden of COVID-19 in Brazil and its states during 2020 and contrasted it to the burden from other causes of disease and injury.

METHODS: We used national surveillance data on COVID-19 cases, hospitalisations and deaths between February/2020 to December/2020. We calculated disability-adjusted life years (DALYs) based on the COVID-19 consensus model and methods developed by the European Burden of Disease Network, which includes mild to moderate, severe, and critical COVID-19 cases, long covid and deaths due to COVID-19. We used Brazil DALYs estimates from the Global Burden of Disease Collaborative Network to compare the COVID-19 burden to that from other causes of disease and injury.

RESULTS: COVID-19's led to 5,445,785 DALYs, or 2,603 DALYs/100,000, with > 99% of the burden caused by mortality. Males accounted for the largest fraction of DALYs (3,214,905 or 59%) and DALYs per 100,000 population (140,594 or 63%). Most populated states experienced the highest DALYs. However, the DALYs per 100,000 population were higher in the states of Rio de Janeiro (4,504 DALYs/100,000), Amapá (4,106 DALYs/100,000) and Roraima (3,981 DALYs/100,000). Assuming no major changes in disease burden from other causes of disease and injury from 2019 to 2020 in Brazil, COVID-19's burden would rank as the leading cause of disability in 2020.

CONCLUSIONS: Compared with studies with similar methodology, our findings showed that Brazil experienced the highest COVID-19 burden (per 100,000 population) in the world. COVID-19 severely impacted Brazil's populational health in 2020, highlighting the lack of effective mitigation efforts.}, } @article {pmid40145003, year = {2025}, author = {Meierkord, A and Schulze, D and Gertler, M and Seybold, J and Mall, MA and Kurth, T and Mockenhaupt, FP and Theuring, S}, title = {Post-infection symptoms up to 24 months after COVID-19: a matched cohort study in Berlin, Germany.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1513664}, pmid = {40145003}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; Berlin/epidemiology ; Adult ; *SARS-CoV-2 ; Aged ; Cohort Studies ; Surveys and Questionnaires ; Retrospective Studies ; Germany/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Time Factors ; }, abstract = {INTRODUCTION: Long-term health consequences after mild COVID-19 are not well described. Our aim was to estimate their prevalence and describe the time course of signs and symptoms for a period of up to 24 months after SARS-CoV-2 infection.

METHODS: We conducted a cohort study matched for age, sex, and test week among individuals who had attended the public COVID-19 test center at Charité-Universitätsmedizin Berlin, Germany. In early 2022, 576 former COVID-19 patients (>95% non-hospitalized) and 302 uninfected individuals responded to a questionnaire on retrospective monthly symptoms since the test date up to 24 months ago.

RESULTS: Symptoms compatible with long COVID were present in 42.9% (247/576) of former COVID-19 patients, compared with 21.2% (64/302) in the uninfected group. In former patients, unadjusted odds ratios (OR) were highest for disturbed taste/smell (OR 9.1 [95% CI: 4.0-21.1]), memory difficulties (OR 5.1 [95% CI: 2.9-8.9]), and shortness of breath at rest (OR 4.5 [95% CI: 1.9-10.6]). In most former COVID-19 patients, symptoms occurred in one coherent period and resolved after a median of 6.5 months, while taste/smell disturbance and neurological/cognitive symptoms showed longer times until recovery. Factors associated with long COVID-compatible symptoms included hospitalization, symptomatic COVID-19 infection, low household income and female sex.

CONCLUSION: Post-infection symptoms in mild COVID-19 patients mostly persist for about half a year, but sometimes longer. Among uninfected individuals who never experienced COVID-19, 21.2% also reported long COVID-compatible symptoms. The current long COVID definition might require revision to prevent misclassification and over-reporting, and to improve diagnosis and prevalence estimates.}, } @article {pmid40144475, year = {2025}, author = {Kurmangaliyeva, S and Madenbayeva, A and Urazayeva, S and Baktikulova, K and Kurmangaliyev, K}, title = {A comparison of Gam-COVID-Vac vaccination and non-vaccination on neurological symptoms and immune response in post-COVID-19 syndrome.}, journal = {Qatar medical journal}, volume = {2025}, number = {1}, pages = {6}, pmid = {40144475}, issn = {0253-8253}, abstract = {The post-COVID-19 syndrome may present with a range of neurological symptoms such as headaches, sleep disorders, and dizziness. The objective of this study was to examine the effectiveness of the Gam-COVID-Vac vaccine in mitigating the neurological symptoms of post-COVID-19 syndrome. The study involved 95 patients diagnosed with the neurological form of long COVID-19, who were divided into two groups according to their vaccination status. The immunological parameters of humoral immunity were evaluated by enzyme-linked immunosorbent assay (ELISA), while the parameters of cellular immunity were evaluated using flow cytometry. Administration of the vaccination resulted in a reduction in clinical symptoms of the neurological form of long COVID-19. Statistically significant differences (p = 0.035) were found in symptoms such as headaches, sleep disturbances, and dizziness, especially in central nervous system (CNS) disorders, between the groups that received the vaccination and those that did not. More than 90% of patients had elevated levels of Receptor Binding Domain (RBD) immunoglobulin G against the viral S-protein (>2,500 BAU/ml), indicating strong humoral immunity regardless of vaccination status. An increase in B-lymphocyte (CD3[-]CD19[+]) counts was noted in both groups, with levels significantly higher in the group that received the vaccination (p < 0.03). Analysis of T-cell profiles and NK (natural killer) cell levels showed no changes. The study suggests that administration of Gam-COVID-Vac vaccination could reduce the occurrence of CNS symptoms in individuals with post-COVID-19 syndrome. Although certain neurological symptoms may continue, immunization has a beneficial influence on their progression. The results emphasize the crucial role of an increased humoral immune response in individuals with post-COVID-19 syndrome, but do not show significant changes in T-cell immune parameters.}, } @article {pmid40143349, year = {2025}, author = {Hannestad, U and Allard, A and Nilsson, K and Rosén, A}, title = {Prevalence of EBV, HHV6, HCMV, HAdV, SARS-CoV-2, and Autoantibodies to Type I Interferon in Sputum from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.}, journal = {Viruses}, volume = {17}, number = {3}, pages = {}, pmid = {40143349}, issn = {1999-4915}, support = {211832Pj01H2//Swedish Cancer Society/ ; 4.3-2019-00201 GD-2020-138//the Swedish Research Council/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/immunology/virology ; Male ; Female ; Middle Aged ; *Interferon Type I/immunology ; Adult ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Herpesvirus 6, Human/immunology ; *Viral Load ; *Autoantibodies/immunology ; *Cytomegalovirus/immunology ; *Herpesvirus 4, Human/immunology ; Aged ; Prevalence ; }, abstract = {An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein-Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies.}, } @article {pmid40142892, year = {2025}, author = {Kang, MA and Lee, SK}, title = {Exploring Coronavirus Disease 2019 Risk Factors: A Text Network Analysis Approach.}, journal = {Journal of clinical medicine}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/jcm14062084}, pmid = {40142892}, issn = {2077-0383}, support = {2021R1A2C2095271//National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; }, abstract = {Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected global health, economies, and societies, necessitating a deeper understanding of the factors influencing its spread and severity. Methods: This study employed text network analysis to examine relationships among various risk factors associated with severe COVID-19. Analyzing a dataset of published studies from January 2020 to December 2021, this study identifies key determinants, including age, hypertension, and pre-existing health conditions, while uncovering their interconnections. Results: The analysis reveals five thematic clusters: biomedical, occupational, demographic, behavioral, and complication-related factors. Temporal trend analysis reveals distinct shifts in research focus over time. In early 2020, studies primarily addressed immediate clinical characteristics and acute complications of COVID-19. By mid-2021, research increasingly emphasized long COVID, highlighting its prolonged symptoms and impact on quality of life. Concurrently, vaccine efficacy became a dominant topic, with studies assessing protection rates against emerging viral variants, such as Alpha, Delta, and Omicron. This evolving landscape underscores the dynamic nature of COVID-19 research and the adaptation of public health strategies accordingly. Conclusions: These findings offer valuable insights for targeted public health interventions, emphasizing the need for tailored strategies to mitigate severe outcomes in high-risk groups. This study demonstrates the potential of text network analysis as a robust tool for synthesizing complex datasets and informing evidence-based decision-making in pandemic preparedness and response.}, } @article {pmid40142660, year = {2025}, author = {Aranda, J and Oriol, I and Vázquez, N and Ramos, K and Suárez, RC and Feria, L and Peñafiel, J and Coloma, A and Borjabad, B and Clivillé, R and Vacas, M and Carratalà, J}, title = {Long COVID in ARDS Survivors: Insights from a Two-Year-Follow-Up Study After the First Wave of the Pandemic.}, journal = {Journal of clinical medicine}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/jcm14061852}, pmid = {40142660}, issn = {2077-0383}, abstract = {Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter cohort of adults with COVID-19 who required hospital admission. Eligible participants underwent clinical interviews, physical examinations, chest radiography, and the 6-min walk test (6MWT). Standardized scales were used to assess post-traumatic stress disorder (PTSD), anxiety, depression, and HRQoL. Results: Out of 1295 patients with COVID-19, 365 developed ARDS, of whom 166 survived. After excluding deaths and loss to follow-up, 95 patients were monitored for 24 months. Over 60% of patients had persistent symptoms, though significant improvements were recorded in quality of life and physical recovery. More than 70% recovered their previous physical capacity, but 15% did not return to their usual lifestyle habits. Symptoms such as arthralgia and fatigue decreased, but cognitive issues, such as memory loss and insomnia, persisted. Radiological improvements were noted, although pulmonary function remained impaired. The prevalence of PTSD and anxiety decreased, while depression remained stable at around 30%. Conclusions: Long COVID continues to impose significant physical, mental, and social challenges. Symptoms like fatigue and anxiety have a profound impact on daily life. Strategies are urgently needed to help patients regain health and resume their normal lives.}, } @article {pmid40142642, year = {2025}, author = {Xholli, A and Perugi, I and Cremonini, F and Londero, AP and Cagnacci, A}, title = {Evaluation of Long-COVID Syndrome in a Cohort of Patients with Endometriosis or Adenomyosis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/jcm14061835}, pmid = {40142642}, issn = {2077-0383}, abstract = {Background: Long-COVID is characterized by the persistency of COVID-19 symptoms beyond 12 weeks, and it is probably consequent to immune dysregulation induced by SARS-CoV-2 infection. Immune dysregulation is associated with and probably involved in the pathogenesis of chronic gynecological conditions like endometriosis and adenomyosis. This study evaluated whether the presence of endometriosis or adenomyosis increases the risk of long-COVID, i.e., the persistence of COVID-19 symptoms beyond 12 weeks since infection. Methods: This retrospective observational study was performed at the outpatient service for endometriosis and chronic pelvic pain, at a university hospital. The diagnosis of endometriosis/adenomyosis was primarily based on clinical symptoms and ultrasonography assessment. Data regarding infection, vaccination, symptoms associated with SARS-CoV-2 infection, and their persistence for a minimum of 12 weeks were collected. Results: This study included 247 women, 149 controls without and 98 cases with endometriosis/adenomyosis. Among these, 194 (116 controls and 78 cases) had suffered from SARS-CoV-2 infection. Rates of infection and vaccination were similar in the two groups. The distribution of the SARS-CoV-2 vaccine was uniform across the two cohorts. COVID-19 patients with endometriosis or adenomyosis exhibited a higher prevalence (p < 0.001) of dyspnea and chest pain. The prevalence of long-COVID beyond 12 weeks was higher in cases than controls (42% vs. 12%; p < 0.001) with chest pain (p < 0.001) and ageusia (p < 0.05), forming the most representative symptoms. Conclusions: Symptoms of long-COVID are more frequent in women with than without endometriosis/adenomyosis.}, } @article {pmid40142631, year = {2025}, author = {Vasiliu, L and Diaconu, A and Onofriescu, M and Dodi, G and Covic, A and Avanu, AE and Voroneanu, L and Vasiliu, V and Kanbay, M and Sascău, RA and Stătescu, C and Covic, AC}, title = {Long-Term Evolution of Post-COVID-19 Echocardiographic Parameters in Patients with Chronic Kidney Disease: A Prospective Comparative Observational Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/jcm14061823}, pmid = {40142631}, issn = {2077-0383}, support = {PN-III-P4-ID-PCE-2020-2393//Ministerul Cercetării și Inovării/ ; }, abstract = {Background/Objectives: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused post-acute sequelae, especially for people with pre-existing conditions, including chronic kidney disease (CKD), which may impact the cardiovascular system. Yet, despite the preliminary description of the general population's long-COVID-19 consequences, data on CKD patients is scarce. The aim of this study was to investigate the longitudinal effects of COVID-19 on echocardiographic parameters of cardiac function and on cardiac biomarkers in patients with CKD. Methods: A total of 163 patients were included in this observational prospective trial (listed under NCT05125913 code): 88 in the COVID-19 group and 75 in the control group. The serial echocardiographic characteristics in patients who survived beyond one year, focused on left and right ventricular systolic function, together with cardiac biomarkers evolution, were compared between the two groups. Results: At baseline, there were no significant differences in left ventricular (LV) function parameters, except for a higher Tei Index in the COVID-19 group (p < 0.01). Right ventricular (RV) systolic dysfunction was more frequent in the COVID-19 group, with worse fractional area change (FAC) (p = 0.01), RV free wall longitudinal strain (RVFWLS) (p = 0.01), and RV Tei Index (p = 0.01). Over time, the control group showed a decline in LV ejection fraction (EF), while the COVID-19 group slightly improved. RV global systolic function was better preserved in the COVID-19 group. To the best of our knowledge, this is the first study that demonstrates a statistically significant increase in LAVi in patients with COVID-19. Conclusions: Prior COVID-19 infection influenced the trajectory of LV and RV function in CKD patients over 12 months, suggesting potential transient myocardial adaptations. While overall cardiac function did not differ significantly between groups, COVID-19 survivors exhibited better preservation of some ventricular function parameters.}, } @article {pmid40141784, year = {2025}, author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A}, title = {Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/life15030439}, pmid = {40141784}, issn = {2075-1729}, abstract = {The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.}, } @article {pmid40141748, year = {2025}, author = {Stasi, C}, title = {Post-COVID-19 Pandemic Sequelae in Liver Diseases.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, doi = {10.3390/life15030403}, pmid = {40141748}, issn = {2075-1729}, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, several studies highlighted a worse prognosis for patients with alterations in liver function tests, especially those with pre-existing liver diseases. However, further studies are needed to define the long-term impact of the COVID-19 pandemic on liver diseases. Long COVID-19 encompasses a wide range of signs and symptoms, including exacerbations of pre-existing chronic conditions or new onset conditions developed after the COVID-19 acute phase. Therefore, the long-term effects of COVID-19 extensively include hepatic manifestations. The co-expression of angiotensin-converting receptor 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) has been demonstrated also in enterocytes, cholangiocytes, and hepatocytes. Studies on the post-COVID-19 sequelae have shown the presence of steatosis and necroinflammation in the liver, concomitantly with an alteration of inflammation, cytolysis and cholestasis indices. Some studies also demonstrated an increased risk for hepatobiliary pathologies, including secondary biliary cholangitis and worsening of the severity of metabolic-associated fatty liver disease (MASLD). Based on these premises, this review aims to provide an overview of the pathophysiological mechanisms contributing to COVID-19-related liver and hepatobiliary damage; explore its implications for liver inflammation and fibrosis, with a particular focus on MASLD and metabolic dysfunction-associated steatohepatitis (MASH); and analyze the short- and long-term COVID-19 sequelae. A literature search was conducted using the PubMed database for relevant studies published in English.}, } @article {pmid40140333, year = {2025}, author = {Wei, C and Jiang, W and Luo, M and Shao, F}, title = {BBB breakdown caused by plasma membrane pore formation.}, journal = {Trends in cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tcb.2025.02.012}, pmid = {40140333}, issn = {1879-3088}, abstract = {The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.}, } @article {pmid40140006, year = {2025}, author = {Velletrani, G and Fiorelli, D and Francavilla, B and Nuccetelli, M and Bernardini, S and Masieri, S and Di Girolamo, S}, title = {Nasal cytological evidence of chronic inflammation in the olfactory cleft in post-viral olfactory dysfunction.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {40140006}, issn = {1434-4726}, abstract = {PURPOSE: This study investigated nasal cytological alterations in patients with persistent post-viral olfactory dysfunction. The primary objective was to evaluate the role of immune dysregulation and chronic local inflammation within the nasal mucosa in sustaining long-term olfactory impairment.

METHODS: An observational case-control study was conducted at the Otorhinolaryngology Department of the University of Rome Tor Vergata. Thirty-six patients with persistent olfactory dysfunction were compared to two control groups: one comprised subjects recovered from SARS-CoV-2 infection without olfactory impairment, and the other included individuals without a history of COVID-19 or olfactory dysfunction. Psychophysical olfactory function was assessed using the TDI (Threshold, Discrimination, and Identification) test. Nasal cytology samples were obtained via nasal brushing at the level of the olfactory cleft and stained using the May-Grunwald-Giemsa technique. Cellular alterations were evaluated using a semiquantitative grading system.

RESULTS: Patients with persistent olfactory dysfunction exhibited increased lymphocytes and neutrophils compared to both control groups, indicating ongoing local inflammation. Ciliocytophthoria was notably present in a significant portion of the olfactory dysfunction group, while absent or minimally present in controls. Eosinophils and mast cells were rare across all groups.

CONCLUSION: Persistent post-viral olfactory dysfunction is associated with sustained immune activation and epithelial damage localized to the olfactory cleft. Elevated lymphocytes, neutrophils, and ciliocytophthoria emphasize the role of chronic inflammation in the pathogenesis of prolonged olfactory deficits. These findings highlight the potential utility of targeted therapies to modulate immune responses and promote olfactory recovery in affected patients.}, } @article {pmid40139915, year = {2025}, author = {Allan-Blitz, LT and Klausner, JD}, title = {Shifting the Focus in Acute SARS-CoV-2 Management to Include Prevention of Long-COVID.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf158}, pmid = {40139915}, issn = {1537-6591}, } @article {pmid40137051, year = {2025}, author = {Kukreti, S and Lu, MT and Yeh, CY and Ko, NY}, title = {Physiological Sensors Equipped in Wearable Devices for Management of Long COVID Persisting Symptoms: Scoping Review.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e69506}, doi = {10.2196/69506}, pmid = {40137051}, issn = {1438-8871}, mesh = {Humans ; *Wearable Electronic Devices ; *COVID-19/therapy/diagnosis ; Monitoring, Physiologic/instrumentation/methods ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Wearable technology has evolved in managing COVID-19, offering early monitoring of key physiological parameters. However, the role of wearables in tracking and managing long COVID is less understood and requires further exploration of their potential.

OBJECTIVE: This review assessed the application and effectiveness of wearable devices in managing long COVID symptoms, focusing on commonly used sensors and their potential for improving long-term patient care.

METHODS: A literature search was conducted across databases including PubMed, Embase, Web of Science, and Cochrane Central, adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines. The search was updated regularly throughout 2024. Abstract and full-text screening and selection were facilitated using Rayyan software developed by Qatar Computing Research Institute. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool to ensure the methodological rigor of the included studies. Data were extracted on study characteristics, wearable devices, sensors used, and monitored physiological parameters, and the results were synthesized in a narrative format.

RESULTS: A total of 1186 articles were identified, and after duplicate removal and screening, 15 studies were initially included, with 11 studies meeting the criteria for final data synthesis. The included studies varied in design, ranging from observational to interventional trials, and involved sample sizes from 3 to 17,667 participants across different countries. In total, 10 different wearable devices were used to monitor long COVID symptoms, capturing key metrics such as heart rate variability, body temperature, sleep, and physical activity. Smartwatches were the most used wearable devices and fitness trackers with electrocardiography and photoplethysmography sensors were used to monitor heart rate, oxygen saturation, and respiratory rate. Of the 10 devices, 4 were Food and Drug Administration-approved, emphasizing the reliability and validation of the physiological data collected. Studies were primarily conducted in the United States and Europe, reflecting significant regional research interest in wearable technology for long COVID management.

CONCLUSIONS: This review highlights the potential of wearable technology in providing continuous and personalized monitoring for long COVID patients. Although wearables show promise in tracking persistent symptoms, further research is needed to improve usability, validate long-term efficacy, and enhance patient engagement.}, } @article {pmid40135045, year = {2025}, author = {Sharma, P and Premkumar, M and Guru, RR and Sandhu, A and Kajal, K and De, A and Rathi, S and Verma, N and Taneja, S and Singh, V and Duseja, AK}, title = {Post COVID Condition and Long-Term COVID-19 Impact on Hepatic Decompensation and Survival in Cirrhosis: A Propensity Matched Observational Study.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {9}, number = {3}, pages = {e70142}, pmid = {40135045}, issn = {2397-9070}, abstract = {AIMS: Patients with cirrhosis are susceptible to decompensation events, including ascites, variceal bleeding (VB), hepatic encephalopathy, or death after COVID-19 infection. Patients may experience post-COVID condition (PCC) with multisystem involvement that persists for at least 2 months.

METHODS: Hospitalized patients with cirrhosis and COVID-19 between January 2021 and January 2023 were assessed for decompensation events and mortality and compared to a propensity-matched cohort of cirrhosis and non-COVID-19 sepsis. Both groups were followed for outcomes over 1 year.

RESULTS: Of 252 patients with Cirrhosis+ COVID-19 (73% men, aged 48.9 ± 13.7 years, 31%-diabetes, 44%-hypertension, 35%-alcohol-associated, 34.5%-metabolic dysfunction-associated steatotic liver disease; MASLD), 72 (28.6%) died in hospital and 180 (71.4%) recovered, similar to Cirrhosis+ non-COVID-sepsis (58/214, 27.1%). Finally,60 (33.3%) met criteria for PCC, 19 (10.5%) had no post COVID-19 sequelae and 101 (56.1%) patients died (N = 45) or were lost to follow up (N = 56). Late Mortality was higher in Cirrhosis+ COVID-19 than non-COVID-sepsis (56.1% vs. 35.3%, p = 0.026). Patients with PCC were aged 47.6 years, 63.3%-men, Charlson Comorbidity Index > 4 (51.7%), 45%-diabetes, 56.7%-hypertension, with 33.3%, 23.3%, and 43.3% in Child-Turcotte-Pugh class A, B and C, respectively. PCC symptoms included persistent dyspnea (34, 43%), cognitive impairment (20, 25.3%), and anxiety (47, 59.4%). On multivariable analysis, predictors of the development of PCC were baseline MELDNa (HR 1.12, 95% CI: 1.05-1.17, p < 0.001) and age (HR 0.9, 95% CI: 0.91-0.99, p = 0.012). Predictors of mortality following COVID-19 recovery were MELDNa (HR 1.03, 95% CI: 1.01-1.05, p = 0.008), age (HR 1.2, 95% CI: 1.1-1.5, p = 0.002) and hypertension (HR 1.63, 95% CI: 1.07-2.49, p = 0.025).

CONCLUSION: COVID-19 is associated with long-term mortality in cirrhosis even after recovery from respiratory infection. Long COVID is seen in a third of COVID-19 survivors in patients with cirrhosis.}, } @article {pmid40134404, year = {2024}, author = {Mithradas, N and Sudhakar, U and Rajaram, V and Ram, S and Ravindran, N}, title = {Galectin-3 as a biomarker for periodontal disease severity in postcoronavirus disease 2019 patients: A clinical and biochemical investigation.}, journal = {Journal of Indian Society of Periodontology}, volume = {28}, number = {5}, pages = {551-556}, pmid = {40134404}, issn = {0972-124X}, abstract = {BACKGROUND: The relationship between coronavirus disease 2019 (COVID-19) and periodontitis has been interesting. Understanding this connection is crucial for comprehensive patient care and highlights the importance of monitoring and addressing oral health issues in an individual's post-COVID-19 recovery. This study compared and evaluated the serum Galectin-3 (Gal-3) levels and clinical parameters in healthy individuals with chronic periodontitis with no history of COVID-19 and post-COVID-19 patients with periodontitis.

MATERIALS AND METHODS: Group I consists of 25 post-COVID-19 patients with Stage II Grade B periodontitis, 25 patients with Stage II Grade B periodontitis without any history of COVID-19 (Group II), and 25 healthy controls (Group III) were recruited for the study. Gal-3 levels in serum were assessed using an enzyme-linked immunosorbent assay (ELISA) kit. Clinical periodontal variables were measured and recorded, including clinical attachment level (CAL), plaque index (PI), and probing pocket depth (PPD). Data analyses were done using the one-way analysis of variance (ANOVA) test and Tukey's honest significant difference post hoc tests.

RESULTS: Group I patients had a higher serum Gal-3 concentrations of 14.757 ng/ml compared to 11.127 ng/ml and 8.673 ng/ml in Group II and Group III, respectively, and the mean difference in Gal-3 levels was statistically significant with P = 0.000. The mean PPD, CAL, and PI were significantly high in Groups I and II compared to Groups II and III with P = 0.000.

CONCLUSION: The current study's findings demonstrated that periodontitis patients and individuals with post-COVID-19 and periodontitis had increased Gal-3 levels in the serum compared to healthy participants. This study highlights the relevance of treating periodontitis during the post-COVID-19/long-COVID era and the need to maintain oral hygiene by identifying possible biomarkers and understanding specific underlying processes.}, } @article {pmid40132524, year = {2025}, author = {Rodríguez-Hernández, C and Guillén-Solà, A and Curbelo, YG and Boza, R and Acuña-Pardo, C and Tejero-Sánchez, M}, title = {[Benefits of a pulmonary rehabilitation program for patients with long COVID: Impact of initial severity, disease duration, and presentation type on clinical outcomes].}, journal = {Rehabilitacion}, volume = {59}, number = {2}, pages = {100900}, doi = {10.1016/j.rh.2025.100900}, pmid = {40132524}, issn = {1578-3278}, abstract = {INTRODUCTION: Two-thirds of patients infected with SARS-CoV-2 experience persistent symptoms after infection.

OBJECTIVES: To study the benefits of a respiratory rehabilitation program (RRP) in patients with long COVID and compare the results based on the time of evolution and clinical presentation.

METHODS: Post-hoc analysis of a prospective cohort of patients with long COVID. Changes were evaluated using the modified Medical Research Council (mMRC) dyspnea scale, the 6-minute walk test (6MWT), maximal inspiratory and expiratory pressures (maxIP and maxEP), and peripheral muscle strength. Statistical tests used: Chi-square, paired and independent t-Student tests, one-way ANOVA, and a general linear model.

RESULTS: Out of 158 patients referred to rehabilitation, 110 (mean age 58.1years; 57.3% women) started the RRP. After the intervention, significant improvements were observed: a reduction of 0.8 points (95%CI: -1.1 to -0.6) on the mMRC dyspnea scale, an increase of 19.6m (95%CI: -0.8 to 39.9) in the 6MWT, 16.8cmH2O (95%CI: 10.3 to 23.2) in maxIP, 22.5cmH2O (95%CI: 15.3 to 29.7) in maxEP, and 5.0kg (95%CI: 3.3 to 6.7) in quadriceps strength. Although these improvements were independent of infection onset and disease duration, patients from the first wave showed more modest improvements.

CONCLUSIONS: The RRP provides clinical and functional benefits for patients with long COVID, regardless of disease duration and initial severity of infection.}, } @article {pmid40132105, year = {2025}, author = {Ono, M and Eguchi, S and Hagiwara, T and Sasayama, D and Washizuka, S}, title = {Risk of Neutropenia Associated With Duloxetine: A Case Study of an 80-Year-Old Man With Depression Related to Long COVID.}, journal = {Journal of clinical psychopharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCP.0000000000001978}, pmid = {40132105}, issn = {1533-712X}, } @article {pmid40130884, year = {2025}, author = {Zahradka, I and Petr, V and Modos, I and Jakubov, K and Dolezal, L and Kalina, S and Viklicky, O}, title = {Prediction and phenotyping of long COVID in kidney transplant recipients: A cross-sectional study.}, journal = {Clinical nephrology}, volume = {}, number = {}, pages = {}, doi = {10.5414/CN111584}, pmid = {40130884}, issn = {0301-0430}, abstract = {AIMS: The aim was to describe the epidemiology, phenotyping, and risk factors of long COVID (LC) in a well-defined cohort of kidney transplant recipients (KTRs) using a novel LC diagnostic method based on self-reported symptoms.

MATERIALS AND METHODS: We conducted a cross-sectional study using an electronic survey to inquire about persisting symptoms following COVID-19. KTRs who survived COVID-19 up to February 8, 2023, were considered for inclusion, and 596 KTRs were enrolled. A brief 35-question screening questionnaire was used. A novel statistical approach based on the factor analysis method was used to make LC diagnosis and identify its clinical phenotypes.

RESULTS: LC was identified in 33.7% of KTRs who responded to the survey. Male sex (OR 0.69, 95% CI 0.48 - 1.0, p = 0.047), more severe COVID-19 (OR 2.48, 95% CI 1.58 - 3.92, p < 0.001), higher body mass index (OR 1.04, 95% CI 1.0 - 1.08, p = 0.031), and corticosteroids (OR 2.8, 95% CI 1.23 - 7.09, p = 0.02) were independently associated with LC development. Eight LC phenotypes were identified based on symptom clustering: fatigue (32.4% of all KTRs), psychiatric (15.9%), cardiovascular (6%), ophthalmic (13.8%), cognitive (17.8%), fibromyalgia-like (11.1%), integumental (10.6%), and malnutritional (6%). The rate of LC was similar in those who had COVID-19 less/more than a year since responding to the survey.

CONCLUSION: A novel method for determining LC diagnosis and its phenotyping was used in a large cohort of KTRs, which showed that a third of KTRs who responded to the survey developed LC after COVID-19. This method may improve diagnosis and future research of LC.}, } @article {pmid40128836, year = {2025}, author = {Formanek, VL and Spector, BM and Zappitelli, G and Wu, Z and Zhao, K}, title = {Designing novel "Smell-Aids" to improve olfactory function in post COVID-19 era.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {169}, pmid = {40128836}, issn = {1741-7015}, mesh = {Humans ; *COVID-19 ; Male ; Female ; Adult ; *Smell/physiology ; Middle Aged ; Odorants ; SARS-CoV-2 ; Young Adult ; Olfaction Disorders ; Aged ; Administration, Intranasal ; }, abstract = {BACKGROUND: Eyeglasses, hearing aids, etc., all serve to enhance the sensory stimuli to enable patients to see or hear things that they would not otherwise be able to, but we have no equivalent technology for olfaction, a pressing issue in the post-COVID era.

METHODS: We attempt to invent "Smell-Aids" by non-invasively enhancing intranasal odorant delivery to the olfactory epithelium, using two prototypes: (a) a nasal foam plug with a diagonal channel embedded to direct air/odor flow upwards to the olfactory region; (b) a clip (similar to what synchronized swimmers use) pinching a critical nasal valve region that may intensify the nasal airflow vortex to the olfactory region.

RESULTS: We first tested these prototypes in counter-balanced orders on 58 healthy subjects, where their measured odor detection thresholds to phenylethyl alcohol significantly improved with both prototypes in subjects with normal smell function (baseline: 8-16.5, n = 30, 12.49 ± 2.8, plug: 14.42 ± 4.9, pinch: 14.73 ± 5.4, p < 0.05), but not in subjects with "super" sensitivity at baseline (> 16.5, n = 28). Next, we tested the prototypes on 54 patients with confirmed olfactory losses (age 21-80 years, median 54.5), the majority of whom (37/54 = 69%) were post-COVID long haulers (infected 12/15/2019 to 10/4/23; persisted 30 to 1260 days, median 22 months). The remaining non-COVID smell losses (n = 17) span significantly longer from 5 months to 27 years (median 8.5 years). The 9-item NIH toolbox odor identification score significantly improved after application of both smell aids (baseline: 4.30 ± 2.27, plug 5.11 ± 2.32, pinch 4.82 ± 2.06, mixed model p < 0.05), especially among the non-COVID cohort. For COVID long haulers, only the nasal plug remained effective (p < 0.05). Subgroup analysis was performed on patients who reported diminished (hyposmia/anosmia 38/54) vs distorted smell (parosmia/phantosmia 27/54, n = 11 reported both) and showed that the nasal plug remains effective for both cohorts (p < 0.05) while the pinch is only effective for the hypo/anosmia cohort (p < 0.05).

CONCLUSIONS: These results preliminarily demonstrated the novelty of improving olfactory function through different peripheral mechanisms for different patient and normative cohorts and may one day lead to an effective over-the-counter smell aid. Enhancing olfactory functions in healthy and patient cohorts through improving intranasal air and odorant delivery.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05920330.}, } @article {pmid40128775, year = {2025}, author = {Exley, J and Stubbs, E and Wittenberg, R and Mays, N}, title = {An international comparison of longitudinal health data collected on long COVID in nine high income countries: a qualitative data analysis.}, journal = {Health research policy and systems}, volume = {23}, number = {1}, pages = {37}, pmid = {40128775}, issn = {1478-4505}, support = {PR-PRU-1217-20602//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Developed Countries ; Longitudinal Studies ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Data Collection/methods ; England/epidemiology ; Data Analysis ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID) presents a significant health challenge. Long-term monitoring is critical to support understanding of the condition, service planning and evaluation. We sought to identify and examine longitudinal health data collected on long COVID to inform potential decisions in England regarding the rationale for data collection, the data collected, the sources from which data were collected and the methods used for collection.

METHODS: We included datasets in high-income countries that experienced similar coronavirus disease 2019 (COVID-19) waves to England pre-vaccine rollout. Relevant datasets were identified through literature searches, the authors' networks and participants' recommendations. We undertook semi-structured interviews with individuals involved in the development and running of the datasets. We held a focus group discussion with representatives of three long COVID patient organisations to capture the perspective of those with long COVID. Emergent findings were tested in a workshop with country interviewees.

RESULTS: We analysed 17 datasets from nine countries (Belgium, Canada, Germany, Italy, the Netherlands, New Zealand, Sweden, Switzerland and the United Kingdom). Datasets sampled different populations, used different data collection tools and measured different outcomes, reflecting different priorities. Most data collection was research (rather than health care system)-funded and time-limited. For datasets linked to specialist services, there was uncertainty surrounding how long these would continue. Definitions of long COVID varied. Patient representatives' favoured self-identification, given challenges in accessing care and receiving a diagnosis; New Zealand's long COVID registry was the only example identified using this approach. Post-exertion malaise, identified by patients as a critical outcome, was absent from all datasets. The lack of patient-reported outcome measures (PROMs) was highlighted as a limitation of datasets reliant on routine health data, although some had developed mechanisms to extend data collection using patient surveys.

CONCLUSIONS: Addressing research questions related to the management of long COVID requires diverse data sources that capture different populations with long COVID over the long-term. No country examined has developed a comprehensive long-term data system for long COVID, and, in many settings, data collection is ending leaving a gap. There is no obvious model for England or other countries to follow, assuming there remains sufficient policy interest in establishing a long-term long COVID patient registry.}, } @article {pmid40126331, year = {2025}, author = {Ribeiro, GJS and Morais, RNG and Abimbola, OG and Dias, NP and Filgueiras, MS and Pinto, AA and Novaes, JF}, title = {Unhealthy Food Consumption Is Associated with Post-Acute Sequelae of COVID-19 in Brazilian Elderly People.}, journal = {Infectious disease reports}, volume = {17}, number = {2}, pages = {}, pmid = {40126331}, issn = {2036-7430}, abstract = {Background/Objectives: The factors associated with post-acute sequelae of COVID-19 (PASC) are not yet fully understood in developing countries. Our objective was to investigate the relationship between food consumption and the occurrence of PASC in Brazilian elderly people. Methods: This cross-sectional study included 1322 elderly people aged 60 or over, infected with SARS-CoV-2 in 2020, living in the state of Roraima in Brazil. Using the Brazilian National Food and Nutrition Surveillance System (SISVAN, in Portuguese) tool, food consumption markers were evaluated. The persistence of post-acute sequelae of COVID-19 was assessed three months after SARS-CoV-2 infection. Poisson regression with robust variance was performed to estimate the prevalence ratio (PR) with a 95% confidence interval (95% CI). Results: Fruit consumption [PR 0.92; 95% CI: 0.85-0.99] was associated with a lower occurrence of PASC, with a significant interaction in individuals aged 60 to 69 years old, not hospitalized, and those without chronic kidney disease. In addition, the consumption of sugar-sweetened beverages [PR 1.23; 95% CI: 1.12-1.35], sandwich cookies, sweets, and treats [PR 1.12; 95% CI 1.03-1.22] was positively associated with the occurrence of PASC in the elderly people, with a significant interaction in individuals living in the capital and without hypercholesterolemia. Conclusions: Unhealthy food consumption was associated with PASC in Brazilian elderly people. An improvement in the diet quality of elderly people is necessary to minimize health complications in PASC.}, } @article {pmid40126325, year = {2025}, author = {Nyasulu, PS and Tamuzi, JL and Oliveira, RKF and Oliveira, SD and Petrosillo, N and de Jesus Perez, V and Dhillon, N and Butrous, G}, title = {COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease.}, journal = {Infectious disease reports}, volume = {17}, number = {2}, pages = {}, pmid = {40126325}, issn = {2036-7430}, abstract = {Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern-both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections.}, } @article {pmid40122540, year = {2025}, author = {McDowell, CP and Tyner, B and Shrestha, S and McManus, L and Comaskey, F and Harrington, P and Walsh, KA and O'Neill, M and Ryan, M}, title = {Effectiveness and tolerance of exercise interventions for long COVID: a systematic review of randomised controlled trials.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e082441}, pmid = {40122540}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/prevention & control/therapy ; *Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVES: To examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.

DESIGN: Systematic review.

DATA SOURCES: Medline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.

Inclusion criteria were: (1) participants with long COVID, as defined by study authors; (2) random assignment to either an exercise intervention or a comparison group and (3) a quantitative measure of at least 1 of the 12 core long COVID outcomes. Exclusion criteria were: (1) signs or symptoms not reasonably attributable to prior SARS-CoV-2 infection; (2) pre-exposure or postexposure prophylaxis for COVID-19 or the prevention of long COVID symptoms and (3) interventions where the primary exercise component is breathing or respiratory muscle training.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data, and studies were narratively synthesised.

RESULTS: Eight studies were included. Follow-up periods ranged from 2 to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two were unclear and two were high. The evidence suggests that exercise interventions lead to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life among people with long COVID. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient relevant information, 1 of 252 participants who received exercise discontinued the intervention due to tolerance-related issues.

CONCLUSION: Available evidence suggests that exercise interventions may be beneficial and tolerable among some people with long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods.}, } @article {pmid40120834, year = {2025}, author = {Pimenta, JC and Beltrami, VA and Silva Oliveira, BD and Queiroz-Junior, CM and Barsalini, J and Teixeira, DC and de Souza-Costa, LP and Diniz Lima, AL and Machado, CA and Schneider Guimarães Parreira, BZ and da Silva Santos, FR and Carvalho Costa, PA and Souza Barbosa Lacerda, L and Gonçalves, MR and de Meira Chaves, I and Gontijo Do Couto, MG and de Melo Costa, VR and Cabacinha Nóbrega, NR and Silva, BL and Fonseca, T and Resende, F and Wnuk, NT and Marim, FM and Oliveira Rocha, FE and Umezu, HL and Campolina-Silva, G and Dos Santos Pereira Andrade, AC and de Aguiar, RS and Jardim Costa, GM and Goulart Guimarães, PP and Ferreira da Silva, GS and Rachid, MA and Vieira, LB and Pinho, V and Teixeira, AL and Teixeira, MM and De Miranda, AS and Costa, VV}, title = {Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2025.03.022}, pmid = {40120834}, issn = {1090-2139}, abstract = {The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as post-COVID syndrome (PCS). Current estimates suggest that more than 100 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10[3] to 3x10[5] PFU/30 μL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10[4] PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.}, } @article {pmid40120171, year = {2025}, author = {Das Sarma, J}, title = {Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties.}, journal = {Virology}, volume = {606}, number = {}, pages = {110499}, doi = {10.1016/j.virol.2025.110499}, pmid = {40120171}, issn = {1096-0341}, abstract = {Coronaviruses have emerged as a significant challenge to human health. While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats, the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology, in addition to its neurological manifestations. In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these viruses is the limited availability of specialized research facilities, emphasizing the need for prototype virus-based models to investigate the pathophysiology. The mouse hepatitis virus (MHV), a member of the β-coronavirus family, serves as an excellent model to unravel the mechanisms underlying virus-induced pathogenesis. This review highlights two decades of research efforts aimed at understanding the pathophysiological mechanism of coronavirus-induced diseases, focusing on the development of targeted recombinant strains to identify the minimal essential motif of the spike protein responsible for fusogenicity and neuropathogenicity. By synthesizing findings from these studies, the review identifies the most promising therapeutic targets against coronaviruses, paving the way for the development of pan-coronavirus antivirals.}, } @article {pmid40120069, year = {2025}, author = {Drysdale, M and Chang, R and Guo, T and Duh, MS and Han, J and Birch, H and Sharpe, C and Liu, D and Kalia, S and Van Dyke, M and DerSarkissian, M and Gillespie, IA}, title = {Impact of treatment of COVID-19 with sotrovimab on post-acute sequelae of COVID-19 (PASC): an analysis of National COVID Cohort Collaborative (N3C) data.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {40120069}, issn = {1439-0973}, abstract = {PURPOSE: To assess the impact of early sotrovimab treatment versus no treatment on the risk of developing post-acute sequelae of COVID-19 (PASC; long COVID) in patients (age ≥ 12 years) with COVID-19 at high risk for progression to severe disease.

METHODS: Retrospective cohort study using the US National COVID Cohort Collaborative (N3C) data. Phase 1 identified and assessed multiple definitions of PASC; Phase 2 evaluated the effectiveness of sotrovimab for reducing the risk of PASC, utilizing definitions from Phase 1. Average treatment effect in the treated (ATT)-weighted Cox proportional hazards regression models were used to compare time to event for PASC between high-risk patients who received sotrovimab treatment between May 26, 2021 and April 5, 2022, and high-risk patients with COVID-19 diagnosed between May 26, 2021 and March 26, 2022 who did not receive any treatment for COVID-19 during the acute phase or any pre-exposure prophylaxis against SARS-CoV-2.

RESULTS: A total of 9,504 sotrovimab-treated and 619,668 untreated patients were included in the main analysis. Most baseline characteristics were balanced between the two cohorts after ATT weighting. The doubly robust ATT-weighted hazard ratio (95% confidence interval) was 0.92 (0.89-0.96) (p < 0.001), indicating that sotrovimab use was associated with a significantly lower risk of PASC. Results remained consistent in sensitivity analyses.

CONCLUSION: In patients at high risk for severe COVID-19, the benefits of early sotrovimab treatment may extend beyond the acute phase of COVID-19 and contribute to the prevention of PASC symptoms.}, } @article {pmid40120036, year = {2025}, author = {Sirotiak, Z and Adamowicz, JL and Thomas, EBK}, title = {Cognitive Impairments in Two Samples of Individuals with ME/CFS and Long COVID: A Comparative Analysis.}, journal = {Journal of clinical psychology in medical settings}, volume = {}, number = {}, pages = {}, pmid = {40120036}, issn = {1573-3572}, abstract = {Cognitive impairments, including memory and concentration difficulties, are common in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. These conditions frequently co-occur, but it remains unclear how cognitive difficulties differ between individuals with ME/CFS, long COVID, both, or neither. The purpose of this study was to examine cognitive impairment presence and type for individuals with and without these conditions. Data from the 2022 and 2023 National Health Interview Survey were analyzed. Participants included 27,512 and 29,404 U.S. adults in 2022 and 2023, respectively. Survey weights and variance estimation variables were utilized and multivariate logistic regression models assessed the likelihood of cognitive difficulty, accounting for sociodemographics and shared variance. Participants from both cohorts were primarily female, white, and non-Hispanic/Latine, with an average age of 48.1 years in both cohorts. ME/CFS (aOR 6.18; 95% CI 4.82-7.93; aOR 5.33; 95% CI 4.04-7.05) and long COVID (aOR 2.01; 95% CI 1.67-2.44; aOR 2.16; 95% CI 1.82-2.56) were significantly associated with reported cognitive difficulties, after controlling for the other condition and sociodemographic factors. Individuals with ME/CFS, particularly those with comorbid long COVID, are especially prone to memory and concentration difficulties.}, } @article {pmid40118860, year = {2025}, author = {Detrille, A and Huvelle, S and van Gils, MJ and Geara, T and Pascal, Q and Snitselaar, J and Bossevot, L and Cavarelli, M and Dereuddre-Bosquet, N and Relouzat, F and Contreras, V and Chapon, C and Caillé, F and Sanders, RW and Le Grand, R and Naninck, T}, title = {Whole-body visualization of SARS-CoV-2 biodistribution in vivo by immunoPET imaging in non-human primates.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2816}, pmid = {40118860}, issn = {2041-1723}, support = {ANR-11-INBS-0008//Agence Nationale de la Recherche (French National Research Agency)/ ; }, mesh = {Animals ; *SARS-CoV-2/immunology ; *COVID-19/virology/diagnostic imaging ; *Positron Emission Tomography Computed Tomography/methods ; Tissue Distribution ; *Antibodies, Monoclonal/pharmacokinetics/immunology ; *Lung/diagnostic imaging/virology/metabolism ; Spike Glycoprotein, Coronavirus/metabolism/immunology ; Humans ; Whole Body Imaging/methods ; Antibodies, Viral/immunology ; Zirconium/pharmacokinetics ; Radioisotopes ; Disease Models, Animal ; }, abstract = {The COVID-19 pandemic has caused at least 780 million cases globally. While available treatments and vaccines have reduced the mortality rate, spread and evolution of the virus are ongoing processes. Despite extensive research, the long-term impact of SARS-CoV-2 infection is still poorly understood and requires further investigation. Routine analysis provides limited access to the tissues of patients, necessitating alternative approaches to investigate viral dissemination in the organism. We address this issue by implementing a whole-body in vivo imaging strategy to longitudinally assess the biodistribution of SARS-CoV-2. We demonstrate in a COVID-19 non-human primate model that a single injection of radiolabeled [[89]Zr]COVA1-27-DFO human monoclonal antibody targeting a preserved epitope of the SARS-CoV-2 spike protein allows longitudinal tracking of the virus by positron emission tomography with computed tomography (PET/CT). Convalescent animals exhibit a persistent [[89]Zr]COVA1-27-DFO PET signal in the lungs, as well as in the brain, three months following infection. This imaging approach also allows viral detection in various organs, including the airways and kidneys, of exposed animals during the acute infection phase. Overall, the technology we developed offers a comprehensive assessment of SARS-CoV-2 distribution in vivo and provides a promising approach for the non-invasive study of long-COVID pathophysiology.}, } @article {pmid40118083, year = {2025}, author = {Khunti, K and Evans, RA and Banerjee, A and van der Feltz-Cornelis, C}, title = {The bidirectional complexity of multiple long-term conditions and post-COVID-19 condition.}, journal = {The Lancet. Respiratory medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2213-2600(25)00047-5}, pmid = {40118083}, issn = {2213-2619}, } @article {pmid40117126, year = {2025}, author = {Bast, E and Jester, DJ and Palacio, A and Krengel, M and Reinhard, M and Ashford, JW}, title = {Gulf War Illness: A Historical Review and Considerations of a Post-Viral Syndrome.}, journal = {Military medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/milmed/usaf092}, pmid = {40117126}, issn = {1930-613X}, abstract = {Gulf War Illness (GWI) is a condition that affects 30-40% of nearly 700,000 Veterans who were deployed to Operations Desert Shield/Storm/Sabre (ODS/S/S) between August 1990 and June 1991 and is characterized by a constellation of symptoms, including fatigue, mood/cognition, chronic pain, gastrointestinal (most frequently referred to as "irritable bowel syndrome"), respiratory, and skin issues. We review the development of various case definitions for GWI, as well as exposure theories. Despite heavy investment in research, both the pathophysiology and underlying cause of GWI remain areas of active inquiry. Similarities have previously been noted in symptomatology between GWI and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and more recently, long COVID (LC), a late effect of infection with the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). These conditions are discussed with respect to the similarities of their symptomatology and pathophysiology. Long COVID is a post-viral syndrome, and ME/CFS is widely considered to be likely post-infectious as well. This comparison leads to the proposal of the hypothesis that GWI may also be post-viral. Given the similarity of GWI and LC, it is possible that Veterans with GWI had an antecedent infection with a virus related to SARS-CoV-2, potentially the Middle East Respiratory Syndrome Coronavirus (MERS) or an ancestor of this virus. The MERS antibodies have been found in dromedary camels in Saudi Arabia since 1983 to the present, including the time of ODS/S/S. There is abundant evidence to support further investigation into this topic.}, } @article {pmid40115993, year = {2025}, author = {Grisanti, SG and Garbarino, S and Bellucci, M and Schenone, C and Candiani, V and Di Lillo, S and Campi, C and Barisione, E and Aloè, T and Tagliabue, E and Serventi, A and Pesce, G and Massucco, S and Cabona, C and Lechiara, A and Uccelli, A and Schenone, A and Piana, M and Benedetti, L}, title = {Neurological long COVID in the outpatient clinic: Is it so long?.}, journal = {European journal of neurology}, volume = {32}, number = {3}, pages = {e16510}, pmid = {40115993}, issn = {1468-1331}, support = {NET-2018-12366666//Ministero della Salute/ ; PE0000006//NEXTGENERATIONEU (NGEU)/ ; ECS00000035//NEXTGENERATIONEU (NGEU)/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; Prospective Studies ; Adult ; Ambulatory Care Facilities/statistics & numerical data ; Follow-Up Studies ; Nervous System Diseases/etiology/epidemiology ; Anosmia/etiology/physiopathology ; SARS-CoV-2 ; Disease Progression ; COVID-19 Vaccines ; }, abstract = {BACKGROUND AND PURPOSE: Neurological involvement in long COVID (coronavirus disease 2019) is well known. In a previous study we identified two subtypes of neurological long COVID, one characterized by memory disturbances, psychological impairment, headache, anosmia and ageusia, and the other characterized by peripheral nervous system involvement, each of which present a different risk factor profile. In this study, we aimed to clarify the persistence of neurological long COVID symptoms with a significantly longer term follow-up.

METHODS: We prospectively collected data from patients with prior COVID-19 infection who showed symptoms of neurological long COVID. We conducted a descriptive analysis to investigate the progression of neurological symptoms over time at 3-, 6-, 12-, and 18-month follow-ups. We performed a k-means clustering analysis on the temporal evolution of the symptoms at 6, 12, and 18 months. Finally, we assessed the difference between the recovery course of vaccinated and non-vaccinated patients by computing the cumulative recovery rate of symptoms in the two groups.

RESULTS: The study confirmed the presence of two subtypes of neurological long COVID. Further, 50% of patients presented a complete resolution of symptoms at 18 months of follow-up, regardless of which subtype of neurological long COVID they had. Vaccination against SARS-Cov-2 appeared to imply a higher overall recovery rate for all neurological symptoms, although the statistical reliability of this finding is hampered by the limited sample size of the unvaccinated patients included in this study.

CONCLUSIONS: Neurological long COVID can undergo complete resolution after 18 months of follow-up in 50% of patients and vaccination can accelerate the recovery.}, } @article {pmid40115713, year = {2025}, author = {AbouAssaly, JR and Masuko, T and Sasai-Masuko, H and Strale, F}, title = {Neurofeedback for COVID-19 Brain Fog: A Secondary Analysis.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e79222}, pmid = {40115713}, issn = {2168-8184}, abstract = {This secondary analysis technical report uses quantitative electroencephalography (qEEG) neurofeedback to treat brain fog, a group of cognitive challenges such as sluggish thinking, memory lapses, confusion, and poor focus, often observed in long COVID. In the original case report, a 34-year-old female patient was administered approximately 15 sessions of Z-score neurofeedback. Pretest and post-test neurofeedback training qEEG reported significant declines in high-beta activity, i.e., beta, Hi beta, beta 1, and beta 3, and notable increases in alpha and theta brainwaves. These improvements were most evident at electrode sites C4, F3, and P3. The patient reported improved attention and memory, reduced anxiety, and less pain, although depression reduction was less. These results suggest that a relatively short program of neurofeedback can assist in shifting the brain from hyperarousal to a calmer, more efficient state. This may potentially offer a non-pharmacological method for treating constant post-COVID brain fog. Additional studies are necessary to validate these findings.}, } @article {pmid40115575, year = {2025}, author = {Arroll, B and Moir, F and Jenkins, E and Menkes, DB}, title = {An audit of 12 cases of long COVID following the lightning process intervention examining benefits and harms.}, journal = {Journal of family medicine and primary care}, volume = {14}, number = {2}, pages = {796-799}, pmid = {40115575}, issn = {2249-4863}, abstract = {To audit the outcomes of patients with long COVID after the lightning process intervention. Retrospective cross-sectional audit. Patients with long COVID were interviewed through telephone regarding their experience and response to the lightning process. Physical, emotional, and overall quality of life; perceived harms of the intervention. None of the 12 participants reported harm from the intervention. 11/12 participants reported being 85% back to normal or more; 8/12 described achieving 85% or greater satisfaction with their emotional, physical, and overall quality of life. 10/12 of the participants reported having heard negative comments about the lightning process but had nonetheless gone ahead with the treatment. This study suggests that the lightning process is a promising and safe intervention for symptoms of long COVID. Primary care clinicians can refer patients for treatment with a high chance of benefit without fear of harm. Randomized, controlled trials are indicated.}, } @article {pmid40114691, year = {2024}, author = {Sales Macêdo, T and Galindo, NM and de Andrade Siqueira Parente, LE and de Sousa Paiva, S and Áfio Caetano, J and Moreira Barros, L}, title = {Lifestyle adaptations in cardiometabolic patients after COVID-19.}, journal = {Revista Cuidarte}, volume = {15}, number = {2}, pages = {e3841}, pmid = {40114691}, issn = {2346-3414}, abstract = {INTRODUCTION: Numerous factors contribute over time to changes in lifestyle behaviors, and the COVID-19 pandemic not only altered individuals' routines but also influenced the factors affecting their chronic conditions.

OBJECTIVE: To understand the perception of patients with cardiometabolic diseases regarding adaptations to their lifestyle after contracting COVID-19.

MATERIALS AND METHODS: This exploratory study with a qualitative approach was conducted with nine patients diagnosed with cardiometabolic diseases who tested positive for COVID-19. Data collection involved semi-structured audio-recorded interviews, which were transcribed and processed using IRAMUTEQ software.

RESULTS: The collective discourse revealed that mass contamination by the coronavirus and subsequent Long COVID triggered significant fears and anxieties, as well as increases in muscle pain, fatigue, and difficulties in maintaining blood pressure and/or glycemic control. These issues directly impacted the daily routines of infected patients. However, there was also an awakening due to changes in lifestyle.

DISCUSSION: The complexity of the experiences reported by infected patients influenced their desire to adopt a healthy lifestyle and seek knowledge.

CONCLUSION: The number of patients affected by COVID-19 in its acute and long phases is concerning for both society and health professionals, highlighting the need to expand strategies aimed at quality care and ensuring adequate monitoring across different spheres of care.}, } @article {pmid40113705, year = {2025}, author = {Adorjan, K and Stubbe, HC}, title = {[Long Covid or mentally ill?].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {5}, pages = {60-65}, doi = {10.1007/s15006-025-4699-8}, pmid = {40113705}, issn = {1613-3560}, } @article {pmid40113382, year = {2025}, author = {Scorza, CA and Scorza, FA and Finsterer, J}, title = {A Prospective Design is Desirable for the Evaluation of Risk Factors, Clinical and Radiological Presentation, and Functional Outcome of Long COVID.}, journal = {The American journal of medicine}, volume = {138}, number = {4}, pages = {e72}, doi = {10.1016/j.amjmed.2024.09.030}, pmid = {40113382}, issn = {1555-7162}, } @article {pmid40113380, year = {2025}, author = {Szarpak, L and Cander, B and Pruc, M}, title = {We Need a Broad Look at Oral Microbiota and Long COVID-19.}, journal = {The American journal of medicine}, volume = {138}, number = {4}, pages = {e70}, doi = {10.1016/j.amjmed.2024.08.034}, pmid = {40113380}, issn = {1555-7162}, } @article {pmid40112553, year = {2025}, author = {Choi, J and Feelemyer, J and Choe, K and Lynch, K and McKnight, C and Yang, LH and Jarlais, DD and Chang, VW}, title = {Anti-vaccine attitudes and COVID-19 vaccine status at the end of the U.S. public health emergency.}, journal = {Vaccine}, volume = {55}, number = {}, pages = {127003}, doi = {10.1016/j.vaccine.2025.127003}, pmid = {40112553}, issn = {1873-2518}, abstract = {INTRODUCTION: Despite the end of the federal COVID-19 public health emergency in May 2023, COVID-19 prevention remains a priority. This study investigates how public vaccination attitudes and perceived COVID-19 risks relate to vaccination status, aiming to identify factors associated with COVID-19 vaccination post-emergency.

METHODS: An online survey was conducted from April to May 2023 among a non-representative, nationally-based sample of MTurk workers. The primary outcome was COVID-19 vaccination status. Variables examined included anti-vaccine attitudes, health status, COVID-19 experiences, and sociodemographic factors. We created a composite measure of anti-vaccine attitudes from 15 items with three levels. Bivariate tests of association and multivariable logistic regression were performed.

RESULTS: A final sample of 989 adults were included in this analysis. In our multivariable model, individuals with higher anti-vaccine attitudes were less likely to be vaccinated against COVID-19 compared to those with low anti-vaccine attitudes (OR = 0.10, 95 % CI 0.04, 0.25). Those who identified as LGBQ+ (OR = 2.55, 95 % CI 1.32, 4.94), had chronic conditions (OR = 2.94, 95 % CI 1.43, 6.01) and had felt stigmatized from COVID-19 infections (OR = 3.33, 95 % CI 1.47, 7.58) were more likely to be vaccinated, even after adjusting for anti-vaccine attitudes. News source, perceived risk of contagion by contact, and long COVID-related factors were not significantly associated with vaccination status in the multivariable model.

DISCUSSION: Our findings highlight the persistent relationship between anti-vaccine attitudes and vaccination status in the "post-pandemic" era. Beyond vaccine attitudes, sexual orientation, chronic conditions, and stigmatization experiences may influence perceived need for protection. Stigma can sometimes reinforce social norms driving vaccination, but this effect is nuanced, particularly with anti-vaccine attitudes. To promote vaccine uptake, interventions should prioritize community support, counter misinformation, and enhance vaccine literacy. Building trust among vulnerable populations is essential, rather than relying on public health messaging that may reinforce social stigma.}, } @article {pmid40110757, year = {2025}, author = {Murano, L and Damico, V and Cossalter, L and Riggio, M and Calabresi, F and Zappia, L and Margosio, V}, title = {The impact of Mindfulness-based stress reduction on Covid-19 survivors. A randomized controlled trial.}, journal = {Annali di igiene : medicina preventiva e di comunita}, volume = {37}, number = {3}, pages = {350-364}, doi = {10.7416/ai.2025.2678}, pmid = {40110757}, issn = {1120-9135}, mesh = {Humans ; *Mindfulness/methods ; *COVID-19/psychology ; Female ; Male ; Middle Aged ; *Stress, Psychological/therapy/prevention & control ; *Anxiety/prevention & control/therapy ; *Depression/therapy ; *Survivors/psychology ; Aged ; Sleep Initiation and Maintenance Disorders/therapy ; Treatment Outcome ; Chronic Pain/therapy/psychology ; Adult ; }, abstract = {INTRODUCTION: Long-COVID represents a clinical condition characterized by the inability of the patient who survived COVID-19 to regain the same state of health prior to the acute infection. Mindfulness-based stress reduction focuses on increasing awareness and acceptance of moment-to-moment experiences including difficult emotions and physical discomfort.

OBJECTIVE: To examine the effects of a Mindfulness-based stress reduction intervention on the functional and psychosocial outcomes of Long-COVID patients.

DESIGN: A two-arm randomized controlled trial with repeated-measures design.

SETTING: Department of Anesthesia and critical care.

PARTICIPANTS: COVID-19 survivors (105 patients).

METHODS: The patients were randomly allocated to either psychoeducation (intervention group) or usual care (control group) (53 vs 52 patients per group). A Mindfulnes program was implemented in the intervention group included an 8-week Mindfulnes-program (2 hours per week) in a group format. Study outcomes included Chronic pain (pain intensity and pain interference) assessed with Brief Pain Inventory (primary outcomes), Anxiety and Depression assessed with Hospital anxiety and depression scale, Insomnia assessed with the Insomnia Severity Index. Data were collected at 6 month and 12 months after Mindfulness-program.

RESULTS: A reduction in pain intensity and pain interference on some activities of daily living were observed 6 and 12 months after intervention. A statistically significant difference emerged in the mean score of symptoms of anxiety in favor of the intervention group (11.28 vs 13.15, t= -3.636, p< .001) at 6 month and at 12 months (10.88 vs 13.41, t= -5.167, p< .001) and in the mean score of the symptoms of depression in favor of the intervention group (9.95 vs 11.23, t= -2.823, p= .007) at 6 month and at 12 months (9.67 vs 10.69, t= -2.458, p= .018). Symptoms of insomnia were statistically reduced 6 months after the Mindfulness-program (score: 53.2 vs 30.4, x= 4.944, p= .026).

CONCLUSIONS: In light of what emerged from our study, we suggest a Mindfulness program in addition to drug therapy to be carried out once a year on patients with consequences of COVID-19. Studies with larger sample sizes that attempt to test a Mindfulness-program twice a year are needed.}, } @article {pmid40108491, year = {2025}, author = {Chaganti, JR and Talekar, TK and Brew, BJ}, title = {Asymmetrical glymphatic dysfunction in patients with long Covid associated neurocognitive impairment- correlation with BBB disruption.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {112}, pmid = {40108491}, issn = {1471-2377}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; Male ; Female ; Middle Aged ; *Blood-Brain Barrier/diagnostic imaging/pathology ; *Glymphatic System/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Aged ; Cognitive Dysfunction/etiology/physiopathology/diagnostic imaging ; Adult ; Post-Acute COVID-19 Syndrome ; Magnetic Resonance Imaging/methods ; Capillary Permeability/physiology ; }, abstract = {BACKGROUND AND PURPOSE: The glymphatic system, a waste clearance pathway, has been implicated in several neurological conditions associated with neuroinflammation. COVID-19 associated neurocognitive impairment, part of the post-acute sequelae of SARS-CoV-2 infection (PASC), is strongly associated with neuroinflammation and disrupted blood-brain barrier (BBB). Several studies have implicated a synergistic interaction between the glymphatic system dysfunction and BBB disruption. In this proof-of-concept study, we investigated the role of the MRI metric diffusion along the perivascular spaces DTI (DTI-ALPS) in patients with PASC and correlated this with the BBB capillary permeability metric- K trans derived from Dynamic contrast enhanced (DCE) perfusion.

MATERIALS AND METHODS: 14 subjects with PASC who had persisting symptoms of anosmia, ageusia, fatigue, and cognitive impairment (CI) and ten healthy age and sex matched controls were recruited. All PASC subjects underwent routine and advanced MR brain imaging at two time points, (3 months +/- 2 weeks) after initial infection - referred as Time Point 1 (TP-1) - and 10 repeated the MRI scan 12 months (+/- 2 weeks) later - referred as Time Point 2 (TP-2), while the controls had MR imaging done only at TP-1. All had mild neurocognitive impairment. In the final analysis we included those who had DTI study at both time points (n-10). MR imaging included DCE perfusion and DTI in addition to anatomical imaging.

STATISTICAL ANALYSIS: Given the small size of the sample and nonnormality of data in the descriptive analyses, nonparametric analyses were used for group comparisons. A two-sample Wilcoxon rank sum test was used to show the differences in DTI-ALPS between the patients and controls in the predefined regions of interest. Spearman's correlation coefficient (rho) was used to assess the correlation between DTI-ALPS index with K trans.

RESULTS: There was significant reduction in the DTI-ALPS index between the patients and controls in the left hemisphere (z = 2.04, p < 0.04). However, there was no significant change over time in the index. There was a strong inverse correlation between the central white matter K trans and DTI-ALPS index (rho = 0.66, p < 0.03).

CONCLUSION: Our study indicates that disordered para vascular drainage, a marker for glymphatic system and BBB damage may contribute to neurocognitive impairment (NCI) among patients with PASC. The DTI-ALPS index, which does not require contrast injection, has the potential to serve as a non-invasive biomarker.}, } @article {pmid40108423, year = {2025}, author = {Breen, JJ and Eisinger, RW and Read, SW and Beigel, J and Palmore, TN and Lane, HC and Menetski, JP and Adam, SJ and Geerling, E and Roy, E and Gerberding, J and Marrazzo, JM}, title = {Navigating the path forward for evidence-based management of long COVID.}, journal = {Nature immunology}, volume = {}, number = {}, pages = {}, pmid = {40108423}, issn = {1529-2916}, } @article {pmid40108145, year = {2025}, author = {Cassiano, LMG and de Paula, JJ and Rosa, DV and Miranda, DM and Romano-Silva, MA and Coimbra, RS}, title = {Vitamin B12 as an epidrug for regulating peripheral blood biomarkers in long COVID-associated visuoconstructive deficit.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {9438}, pmid = {40108145}, issn = {2045-2322}, support = {88881.504749/2020-01. 9951//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 408817/2022-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 406935/2022//Instituto Nacional de Ciência e Tecnologia em Nanotecnologias Responsáveis/ ; 406935/2022//Instituto Nacional de Ciência e Tecnologia em Nanotecnologias Responsáveis/ ; VPPCB-005-FIO-20-2-115//INOVA FIOCRUZ/ ; }, mesh = {Humans ; *Vitamin B 12/blood ; *COVID-19/blood/virology ; Male ; *Biomarkers/blood ; Female ; Middle Aged ; Aged ; SARS-CoV-2/isolation & purification ; Chemokine CCL11/blood ; COVID-19 Drug Treatment ; Adult ; Cognitive Dysfunction/blood ; }, abstract = {Approximately four months after recovering from a mild COVID-19 infection, around 25% of individuals developed visuoconstructive deficit (VCD), which was found to be correlated with an increase in peripheral immune markers and alterations in structural and metabolic brain imaging. Recently, it has been demonstrated that supplemental vitamin B12 regulates hyperinflammation during moderate and severe COVID-19 through methyl-dependent epigenetic mechanisms. Herein, whole peripheral blood cultures were produced using samples obtained from patients with confirmed persistent VCD, and controls without impairment, between 10 and 16 months after mild COVID-19. This experimental model was used to assess the leukocyte expression patterns of 11 biomarkers previously associated with VCD in long COVID and explore the potential of pharmacological B12 in regulating these genes. The results showed that patients with persistent VCD displayed continued upregulation of CCL11 and LIF compared to controls. It is worth noting that elevated serum levels of CCL11 have been previously linked to age-related neurodegenerative diseases. Notably, the addition of 1 nM of vitamin B12 to blood cultures from individuals with VCD normalized the mRNA levels of CCL11, upregulated the neuroprotective HGF, and, to a lesser extent, downregulated CSF2 and CXCL10. There was an inverse correlation observed between CCL11 mRNA levels and methylation levels of specific cytosines in its promoter region. These findings underscore the significance of systemic inflammation in persistent VCD associated with long COVID. Moreover, the study provides evidence suggesting that B12, acting as an epidrug, shows promise as a therapeutic approach for addressing this cognitive impairment.}, } @article {pmid40107677, year = {2025}, author = {Pasquier, JC and Plourde, M and Ramanathan, S and Chaillet, N and Boivin, G and Laforest-Lapointe, I and Allard-Chamard, H and Baron, G and Beaulieu, JF and Fülöp, T and Généreux, M and Mâsse, B and Robitaille, J and Valiquette, L and Bilodeau, S and H Buch, D and Piche, A}, title = {P robiotics i nfluencing r esponse of a ntibodies over t ime in s eniors after CO VID-19 v accine (PIRATES-COV): a randomised controlled trial protocol.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e088231}, doi = {10.1136/bmjopen-2024-088231}, pmid = {40107677}, issn = {2044-6055}, mesh = {Humans ; Aged ; *COVID-19/prevention & control ; Aged, 80 and over ; *Probiotics/therapeutic use ; Double-Blind Method ; *SARS-CoV-2/immunology ; Male ; Female ; *COVID-19 Vaccines/immunology ; Quebec ; Antibodies, Viral/blood ; Lacticaseibacillus casei/immunology ; Lacticaseibacillus rhamnosus ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: The elderly are particularly vulnerable to morbidity and mortality from COVID-19, the disease caused by the SARS-CoV-2. Approximately 20% of the elderly showed no antibodies 3-5 months post-second dose of the COVID-19 vaccine. As probiotics have been shown to increase influenza-specific antibody levels post-influenza vaccination, we aim to reduce the percentage of participants without antibodies against the SARS-CoV-2 spike protein receptor-binding domain (anti-S1-RBD) at 6 months post-vaccination.

METHODS AND ANALYSIS: Our study design is a double-blind randomised controlled trial, using intention-to-treat analysis. Eligible participants are a purposive sample of 688 adults aged 65-89 years, in Quebec, Canada, not diagnosed with COVID-19 in the 3 months prior to recruitment and who wish to receive a government-recommended mRNA booster (Pfizer-BioNTech, Moderna) vaccine. The intervention consists of one capsule/day of a probiotic dietary supplement of Lacticaseibacillus rhamnosus and Lacticaseibacillus casei 6×10[9] CFU/capsule or a placebo, for 15 days pre-booster and post-booster vaccine. All participants provide dried blood spot samples at three timepoints (inclusion, 3 and 6 months post-vaccination) and a stool sample for microbiome analysis. A subgroup of 100 participants living near Sherbrooke, Quebec, is expected to volunteer for two onsite blood-test visits (at inclusion and 6 months post-vaccination). The primary outcome is the percentage of participants without anti-S1-RBD antibodies at 6 months post-vaccination. Secondary outcomes include longitudinal analysis of anti-S1-RBD and anti-N antibodies at three timepoints. In the subgroup, serum levels of neutralising antibodies will be determined at inclusion and 6 months post-vaccination. Probiotic and vaccine side effects are monitored. At the end of the study, we expect to identify the adjuvant effect of probiotic on vaccine-induced immune response.

ETHICS AND DISSEMINATION: The study was approved by Research Ethics Board of the Centre Intégré Universitaire de Santé et des Services Sociaux de l'Estrie- Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de l'Estrie-CHUS) and the CHU de Québec-Université Laval # MP-31-2022-4598 as well as Health Canada. All participants will provide informed consent. Results will be disseminated to the scientific community and to all networks related in this research.

TRIAL REGISTRATION NUMBER: NCT05195151.}, } @article {pmid40107657, year = {2025}, author = {Mischke, M and Zaehle, T}, title = {Evaluating the Efficacy of Repetitive Anodal Transcranial Direct Current Stimulation on Cognitive Fatigue in Long COVID: A Randomized Controlled Trial.}, journal = {Brain stimulation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.brs.2025.03.011}, pmid = {40107657}, issn = {1876-4754}, } @article {pmid40107360, year = {2025}, author = {Pons-Fuster, E and Martinez-Rodriguez, R and Gimeno-Arias, L and Alcaraz, MJ and Moreno, M and Gómez, JM and Pelaez, A and García, E and Tomás, C and Muñoz, A and Martínez-Sánchez, MV and Ruiz-Lorente, I and Ceballos, D and Minguela, A and Bernal, E}, title = {HLA-A*03 may confer protection against long COVID through an enhanced immune response.}, journal = {Infectious diseases now}, volume = {55}, number = {4}, pages = {105057}, doi = {10.1016/j.idnow.2025.105057}, pmid = {40107360}, issn = {2666-9919}, abstract = {BACKGROUND: The COVID-19 pandemic has led to widespread infection, with a significant subset of patients developing persistent symptoms known as Long COVID. Understanding the genetic factors influencing Long COVID susceptibility and severity is crucial for development of targeted interventions.

OBJECTIVE: This study aimed to evaluate the impact of HLA alleles, KIR receptors, and their interactions on the development of Long COVID in patients from southeastern Spain having contracted COVID-19 during the early 2020 pandemic wave.

METHODS: A cross-sectional prospective study enrolled 153 COVID-19 patients. Three months post-infection, HLA-A, -B, -C, KIR genotyping and immunological variables were analyzed using serum and blood samples. Long COVID was diagnosed three years post- infection based on persistent symptoms.

RESULTS: Among the participants, 71 developed Long COVID. HLA-A*03 was less frequent in Long COVID compared to non-Long COVID patients (10.7 % vs. 30.5 %, p = 0.001). Patients with HLA-A*03 had a higher percentage of CD8[+] T cells than patients with other allotypes (33.6 ± 13.4 % vs 28.7 ± 10.8 %, p = 0.033) and showed lower expression of KIR2DL1(1265 ± 547 vs 1465 ± 414 MFI, p = 0.031) and KIR3DL1 (300.6 ± 125.0 vs 398.9 ± 131.0 MFI, p = 0.047). Moreover, NK cells in HLA-A*03 patients showed lower expression of the TIGIT inhibitory receptor (73.7 ± 12.2 % vs 78.2 ± 10.8 %, p = 0.046).

CONCLUSION: HLA-A*03 may play a protective role against Long COVID, potentially through enhanced immune responses involving CD8[+] T cells and NK cells. Further research in larger, diverse cohorts is needed to validate these findings and to refine personalized medicine strategies for managing COVID-19 sequelae.}, } @article {pmid40107106, year = {2025}, author = {Lu, C and Deng, W and Qiao, Z and Sun, W and Xu, W and Li, T and Wang, F}, title = {Effects of early-life air pollution exposure on childhood COVID-19 infection and sequelae in China.}, journal = {Journal of hazardous materials}, volume = {491}, number = {}, pages = {137940}, doi = {10.1016/j.jhazmat.2025.137940}, pmid = {40107106}, issn = {1873-3336}, abstract = {BACKGROUND: While ambient air pollution has been associated with COVID-19 outcomes, the role of early-life exposure in childhood COVID-19 infection and sequelae remains unexplored.

OBJECTIVES: To assess the associations between early-life exposure to ambient air pollutants during and childhood COVID-19 infection and sequelae.

METHODS: This cross-sectional retrospective cohort study surveyed families with children aged 3-6 years in families across nine Chinese cities between December 2019 and May 2023. The primary outcomes were doctor-diagnosed childhood COVID-19 infection and sequelae. Individual exposure to PM2.5, PM2.5-10, PM10, SO2, NO2, CO, O3, and temperature were estimated.

RESULTS: Among 20,012 children from 60,036 participants, 5.81 % were diagnosed with COVID-19 infection, and 1.72 % had sequelae. Prenatal CO exposure was associated with higher infection risk (OR: 1.33; 95 % CI: 1.05-1.69 per IQR increase). SO2 exposure during the first trimester (OR: 3.02; 95 % CI: 1.20-7.61), second trimester (OR: 4.00; 95 % CI: 1.56-10.27) and third trimester (OR: 3.84; 95 % CI: 1.69-8.76) of pregnancy and the first year of life (OR: 8.43; 95 % CI: 1.80-39.48) was strongly associated with sequelae. Pre-existing allergies and coarser particulate matter (PM2.5-10 and PM10) amplified these associations. High relative humidity significantly increased the effect of exposure to NO2 during four-six months before pregnancy and the second trimester of pregnancy, as well as O3 exposure during the first year on childhood COVID-19 infection.

CONCLUSIONS: Early-life exposure to air pollutants and interactions with allergic conditions and coarser particles influence childhood COVID-19 risks.}, } @article {pmid40105889, year = {2025}, author = {Mueller, MR and Ganesh, R and Beckman, TJ and Hurt, RT}, title = {Long COVID: emerging pathophysiological mechanisms.}, journal = {Minerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0026-4806.25.09539-4}, pmid = {40105889}, issn = {1827-1669}, abstract = {Post-COVID conditions, also termed "long COVID," are a heterogeneous set of conditions persisting greater than 28 days after initial infection. These conditions, which include fatigue, brain fog, orthostatic intolerance, and pain, are a significant source of morbidity and limited function worldwide. Nonetheless, both the pathophysiology and treatment of long COVID remain poorly understood. Several pathophysiologic mechanisms have been proposed including neuroinflammatory drivers, endothelial dysfunction, neurotransmitter dysregulation, mitochondrial dysfunction, autonomic dysfunction, and central sensitization. In this article, we present a conceptual framework for evaluation of long COVID symptoms, as well as the evidence behind their proposed pathophysiologic mechanisms. Patients may struggle with one or more of the proposed mechanisms listed above, and the contributions from each process may vary depending on the patient. Although no FDA-approved therapies exist for long COVID, we review several potential promising and mechanistically plausible therapies.}, } @article {pmid40102496, year = {2025}, author = {Niemczak, C and Skoe, E and Leigh, S and Zhang, L and Dotzenrod, M and Kieley, A and Stone, S and Parsonnet, J and Martin, C and Ealer, C and Clavier, O and Gui, J and Waszkiewicz, A and Roth, R and Buckey, J}, title = {Altered auditory brainstem responses are post-acute sequela of SARS-CoV-2 (PASC).}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {9387}, pmid = {40102496}, issn = {2045-2322}, support = {250-8006//Hitchcock Foundation/ ; }, mesh = {Humans ; Female ; *Evoked Potentials, Auditory, Brain Stem/physiology ; Male ; Adult ; Middle Aged ; *COVID-19/physiopathology/complications ; *SARS-CoV-2/isolation & purification ; *Tinnitus/physiopathology ; Post-Acute COVID-19 Syndrome ; Auditory Threshold/physiology ; }, abstract = {The Post-acute Sequela of SARS-CoV-2 (PASC) syndrome, also known as Long-COVID, often presents with subjective symptoms such as brain fog and cognitive fatigue. Increased tinnitus, and decreased hearing in noise ability also occur with PASC, yet whether auditory manifestations of PASC are linked with the cognitive symptoms is not known. Electrophysiology, specifically the Auditory Brainstem Response (ABR), provides objective measures of auditory processing. We hypothesized that ABR findings would be linked to PASC and with subjective feelings of cognitive fatigue. Eighty-two individuals, 37 with PASC (mean age: 47.5, Female: 83%) and 45 healthy controls (mean age: 38.5, Female: 76%), were studied with an auditory test battery that included audiometry and ABR measures. Peripheral hearing thresholds did not differ between groups. The PASC group had a higher prevalence of tinnitus, anxiety, depression, and hearing handicap in addition to increased subjective cognitive fatigue. ABR latency findings showed a significantly greater increase in the wave V latency for PASC subjects when a fast (61.1 clicks/sec) compared to a slow click (21.1 clicks/sec) was used. The increase in latency correlated with cognitive fatigue scores and predicted PASC status. The ABR V/I amplitude ratio was examined as a measure of central gain. Although these ratios were not significantly elevated in the full PASC group, to minimize the cofounding effect of age, the cohort was median split on age. Elevated V/I amplitude ratios were significant predictors of both predicted PASC group classification and cognitive fatigue scores in the younger PASC subjects compared to age-matched controls providing evidence of elevated central gain in younger individuals with PASC. More frequent tinnitus also significantly predicted higher subjective cognitive fatigue scores. Our findings suggest that PASC may alter the central auditory pathway and lead to slower conduction and elevated auditory neurophysiology responses at the midbrain, a pattern associated with the typical aging process. This study marks a significant stride toward establishing an objective measure of subjective cognitive fatigue through assessment of the central auditory system.}, } @article {pmid40101664, year = {2025}, author = {Mkoma, GF and Goldschmidt, MI and Petersen, JH and Benfield, T and Cederström, A and Rostila, M and Agyemang, C and Norredam, M}, title = {Socioeconomic disparities in long COVID diagnosis among ethnic minorities in Denmark.}, journal = {Social science & medicine (1982)}, volume = {372}, number = {}, pages = {117944}, doi = {10.1016/j.socscimed.2025.117944}, pmid = {40101664}, issn = {1873-5347}, abstract = {BACKGROUND: Low socioeconomic status has been demonstrated as a risk factor for COVID-19 severity and mortality. However, whether socioeconomic disparities also influence the risk of long COVID diagnosis among ethnic minorities compared to the native majority population remains unclear.

METHODS: We conducted a nationwide register-based cohort study in Denmark, including individuals with a first-time COVID-19 diagnosis between January 2020 and August 2022. The risk of long COVID diagnosis among ethnic groups (defined by country of birth) was compared according to socioeconomic status.

RESULTS: Among 2 287 175 COVID-19 cases, 4579 were diagnosed with long COVID. The risk of long COVID diagnosis did not significantly differ by income or educational attainment for most ethnic groups. However, among low-income individuals, migrants had a higher risk of long COVID than native Danes, particularly Eastern Europeans (HRadjusted 1.45, 95 % CI [1.25,1.70], p < 0.001), Southeast Asians (HRadjusted 2.08, 95 % CI [1.32,3.28], p = 0.002), Middle Easterners (HRadjusted 1.65, 95 % CI [1.31,2.07], p < 0.001), and North Africans (HRadjusted 1.68, 95 % CI [1.24,2.27], p < 0.001). Additionally, migrant workers (Eastern European, Middle Eastern, and South Asian) in occupational sectors such as "economy, business, and administration", "operator, driver and transportation service", "sales and customer service", "general office and secretarial service" and "education" had a higher long COVID risk than native Danish workers in the same workplaces.

IMPLICATIONS: These findings highlight the need to address ethnic disparities in long COVID, particularly among migrants with low income. Workplace interventions and policies targeting work-related vulnerabilities could help reduce the disproportionate burden of long COVID among migrant workers.}, } @article {pmid40100769, year = {2025}, author = {Nandula, SR and Brichacek, B and Sen, S}, title = {Podocyte-Specific Protein Expression in Urine Exosome Acts as a Marker for Renal Injury in Post-COVID State.}, journal = {Metabolic syndrome and related disorders}, volume = {}, number = {}, pages = {}, doi = {10.1089/met.2024.0199}, pmid = {40100769}, issn = {1557-8518}, abstract = {Introduction: Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, in vitro, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Methods: Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Results: Urine exosomal podocalyxin levels were significantly high at 10 week (n = 18; P = 0.001), 6 month (n = 25; P = 0.003) and 12 month (n = 14; P = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (n = 18; P = 0.001) and 12 month (n = 14; P = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Conclusion: Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.}, } @article {pmid40099884, year = {2025}, author = {Alvin, JR and Ramírez-Flores, CJ and Mendina, CA and Audhya, A and Knoll, LJ and Lettman, MM}, title = {Toxoplasmosis accelerates the progression of hereditary spastic paraplegia.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0082624}, doi = {10.1128/msphere.00826-24}, pmid = {40099884}, issn = {2379-5042}, abstract = {The parasitic protozoa Toxoplasma gondii chronically infects the central nervous system of an estimated one-third of the human population. Infection is generally subclinical, but immunocompromised individuals can experience a variety of neurological symptoms. Meta-analyses of T. gondii seropositivity have suggested a correlation between T. gondii infection and neurologic disease. Although mechanistic studies on the relationship between T. gondii infection and neurologic disease have been attempted in mice, they are particularly susceptible to T. gondii, making them an effective model for investigating mechanisms of infection, but not ideal for examining the relationship between long-term chronic T. gondii infection and neurologic disease. Rats more closely mimic human T. gondii cyst levels after acute infection, but a lack of rat models for neurologic disease has limited studies on the interplay between T. gondii infection and neurologic disease progression. We have employed a previously characterized rat model of a complex form of hereditary spastic paraplegia (HSP), a class of neurodegenerative disorders that cause axonal degeneration and lower limb spasticity, in order to assess the effect of chronic T. gondii infection on neurodegenerative disease. We find that infected rats with hereditary spastic paraplegia exhibit significantly exacerbated behavioral and neuromorphological HSP symptoms compared with uninfected HSP mutant rats, with little correlative effect in infected versus uninfected control animals. We further find that all infected rats, regardless of genotype, exhibit a robust immune response to T. gondii infection, presenting with parasite levels below the limit of detection of multiple assays of parasitemia and exhibiting no detectable increase in neuroinflammation 7 weeks post-infection. These results suggest that chronic undetected T. gondii infection may exacerbate neurodegenerative disease even in immunocompetent individuals and may contribute to neurodegenerative disease heterogeneity.IMPORTANCEThe long-term consequences of previous acute infections are poorly understood but are becoming increasingly appreciated, particularly in the era of long COVID. Altered progression of other diseases later in life may be among the long-term consequences of previous infections. Here, we investigate the relationship between previous infections with the parasite Toxoplasma gondii, which infects ~30% of the global population, and neurodegenerative disease using a rat model of hereditary spastic paraplegia (HSP). We find that previous infections with T. gondii accelerate motor dysfunction in HSP rats, despite robust clearance of the parasite by infected rats. Our results suggest that previously cleared infections may alter the progression of other diseases later in life and contribute to neurodegenerative disease heterogeneity.}, } @article {pmid40099157, year = {2025}, author = {Miwa, K}, title = {Corrigendum to "Oral minocycline therapy as first-line treatment in patients with Myalgic encephalomyelitis and long COVID: A pilot study" [eNeurologicalSci 38 (2025) 100537].}, journal = {eNeurologicalSci}, volume = {38}, number = {}, pages = {100557}, doi = {10.1016/j.ensci.2025.100557}, pmid = {40099157}, issn = {2405-6502}, abstract = {[This corrects the article DOI: 10.1016/j.ensci.2024.100537.].}, } @article {pmid40099151, year = {2024}, author = {De Las Salas, R}, title = {[[Long covid: new tool to assess clinical manifestations and conditions]].}, journal = {Revista de salud publica (Bogota, Colombia)}, volume = {26}, number = {2}, pages = {116477}, pmid = {40099151}, issn = {2539-3596}, } @article {pmid40097216, year = {2025}, author = {Jiang, T and Yang, Q and Li, F}, title = {[Tongtiao acupuncture-moxibustion method for 28 cases of long COVID-19 olfactory dysfunction].}, journal = {Zhongguo zhen jiu = Chinese acupuncture & moxibustion}, volume = {45}, number = {3}, pages = {331-334}, doi = {10.13703/j.0255-2930.20240429-k0004}, pmid = {40097216}, issn = {0255-2930}, mesh = {Humans ; *COVID-19/therapy/complications ; Male ; Female ; *Acupuncture Therapy ; Middle Aged ; Adult ; *Moxibustion ; *Acupuncture Points ; Aged ; *Olfaction Disorders/therapy/etiology ; *SARS-CoV-2 ; Treatment Outcome ; }, abstract = {OBJECTIVE: To observe the clinical efficacy of Tongtiao acupuncture-moxibustion method for long COVID-19 olfactory dysfunction.

METHODS: A total of 28 patients with long COVID-19 olfactory dysfunction were selected and treated with Tongtiao acupuncture-moxibustion therapy (regulating orifices, invigorating the brain, and regulating qi and blood). Acupoints included Yintang (GV24[+]), Baihui (GV20), Fengfu (GV16), Qihai (CV6) and bilateral Yingxiang (LI20), Fengchi (GB20), Xuehai (SP10), Zusanli (ST36). Deep needling to the periosteum of the nasal bone was performed at Yintang (EX-HN3), with warming needle moxibustion applied. Each treatment lasted 40 min, administered once daily for 6 days per week, followed by a 1-day rest, over 4 consecutive weeks. T&T olfactory test scores, TCM symptom scores, serum cortisol levels, Hamilton depression scale (HAMD) scores, and Hamilton anxiety scale (HAMA) scores were compared before and after treatment. Clinical effect was evaluated based on T&T olfactory test grading.

RESULTS: Compared before treatment, the T&T olfactory test scores, each TCM symptom scores, HAMD scores, and HAMA scores were decreased after treatment (P<0.01, P<0.05), while serum cortisol level was increased (P<0.01). The total effective rate was 96.4% (27/28).

CONCLUSION: Tongtiao acupuncture method could effectively alleviate symptoms of long COVID-19 olfactory dysfunction, increase serum cortisol level, and relieve anxiety and depressive symptoms.}, } @article {pmid40097195, year = {2025}, author = {Woodrow, M and Ziauddeen, N and Smith, D and Alwan, NA}, title = {Exploring Long Covid Prevalence and Patient Uncertainty by Sociodemographic Characteristics Using GP Patient Survey Data.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70202}, doi = {10.1111/hex.70202}, pmid = {40097195}, issn = {1369-7625}, support = {//This work forms part of M.W.'s PhD which is funded by a University of Southampton Presidential Scholarship./ ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; Adult ; *COVID-19/epidemiology ; Uncertainty ; England/epidemiology ; Prevalence ; Aged ; Adolescent ; Young Adult ; Sociodemographic Factors ; Surveys and Questionnaires ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Socioeconomic Factors ; General Practice ; }, abstract = {BACKGROUND: The high global burden of Long Covid (LC) has significant implications for population well-being, health care, social care and national economies.

AIM: To explore associations between patient sociodemographic and health characteristics with two outcomes: having LC and expressing uncertainty about having LC, as described by general practice (GP) survey respondents.

DESIGN AND SETTING: Analysis of GP Patient Survey (England), a random sample of 759,149 patients aged 16 years+ registered with a GP in England (2023).

METHOD: Multivariable logistic regression modelling comparing those with and without LC, and those who were unsure in relation to patient characteristics.

RESULTS: 4.8% of respondents reported having LC, and 9.1% were unsure. Significant adjusted associations indicating higher risk of LC included age (highest odds 35-54 years), sex (females), ethnicity (White Gypsy/Irish Traveller, mixed/multiple ethnic groups), sexual orientation (gay/lesbian or bisexual), living in a deprived area, being a carer or a parent and having a long-term condition (LTC). Those aged ≤ 25 years, males, non-binary, heterosexual, not parents or carers, from other White, Indian, Bangladeshi, Chinese, Black or Arab backgrounds, former and current smokers, and with no defined LTC were more likely in adjusted analysis to be unsure about having LC compared to answering 'yes'.

CONCLUSION: There is an unequal distribution of LC in England, with the condition being more prevalent in minoritised and disadvantaged groups. There are also high levels of uncertainty about having LC. Improved awareness is needed amongst the general population and health care professionals to ensure those most vulnerable in society are identified and provided with care and support.

The analysis builds on previous studies co-created with people with lived experience. A public contributor advised on discussions on dissemination towards optimal impact of this study's findings. Study findings will inform the next phases of the research in which the research questions and design will be co-created with public partners.

HOW THIS FITS IN: In England there is high prevalence of Long Covid, a COVID-19 infection-induced chronic condition that can limit daily activities significantly. The burden of ill health from Long Covid is unequal, with minoritised groups experiencing higher prevalence. This study adds further evidence of inequality in the prevalence of Long Covid, but also reveals that there are more people who are unsure whether they have Long Covid than those who are confident they have it, with certain groups that are already disadvantaged being more likely to be uncertain if they have the condition. Findings underline a need for greater awareness of Long Covid amongst the public and health care professionals, and for diagnosis, treatment and support to be better distributed according to need.}, } @article {pmid40095507, year = {2025}, author = {Kapel, JS and Stokholm, R and Elmengaard, B and Nochi, Z and Olsen, RJ and Foldager, CB}, title = {Individualized Algorithm-Based Intermittent Hypoxia Improves Quality of Life in Patients Suffering from Long-Term Sequelae After COVID-19 Infection.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, pmid = {40095507}, issn = {2077-0383}, support = {10.46540/3165-00221B//The project was partly supported by the Independent Research Fund Denmark/ ; }, abstract = {Background/Objectives: Post-COVID-19 condition (PCC), also known as long COVID, has emerged as a recognized syndrome affecting millions of people worldwide, significantly impairing their quality of life. Currently, no effective therapeutic options are available to manage this condition. The objective of the present study was to evaluate the long-term effects of personalized, algorithm-based intermittent hypoxia-hyperoxia conditioning (IHHC) on quality of life and pain in patients with PCC. Methods: This open-label cohort study included 199 PCC patients, aged 11-87 years (female-to-male ratio: 67:33) and experiencing moderate-to-severe fatigue, between 1 January 2020 and 31 December 2023. Each patient received an algorithm-based treatment plan tailored to their demographics, symptom duration, and baseline pain (NRS) and quality of life (SF-36) scores. Patients received an average of six treatment sessions (range: 2-21), each consisting of intermittent hypoxic-hyperoxic cycles, with hypoxia (9-13% O2) lasting 3-8 min and hyperoxia (34-36% O2) lasting 1-3 min. The primary outcomes were changes in the NRS and SF-36 scores at the 6-week and 6-month follow-ups. Results: At the 6-week follow-up after treatment initiation, the SF-36 scores increased by 102 points (p < 0.001, 95% CI: 78.4-127), and this improvement persisted at the 6-month follow-up (Δ106, p < 0.001, 95% CI: 57.0-154). Pain was reduced by 28-32% at both follow-up time points, exceeding the clinically relevant threshold. Health transition scores indicated a patient-perceived improvement in health status. Conclusions: In this study, a personalized, algorithm-based IHHC alleviated pain and improved quality of life in patients suffering from persistent long-term sequelae after COVID-19 infection. The effects were sustained for up to six months. Further research is warranted to elucidate the mechanisms underlying IHHC's therapeutic effects in this patient population.}, } @article {pmid40094929, year = {2025}, author = {Patrascu, R and Dumitru, CS}, title = {Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, pmid = {40094929}, issn = {2077-0383}, abstract = {This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies.}, } @article {pmid40094893, year = {2025}, author = {Mara, G and Nini, G and Cotoraci, C}, title = {Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations.}, journal = {Journal of clinical medicine}, volume = {14}, number = {5}, pages = {}, doi = {10.3390/jcm14051446}, pmid = {40094893}, issn = {2077-0383}, abstract = {Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during the acute phase and in long-term recovery, focusing on their impact on clinical management and outcomes. Methods: This systematic review examined studies sourced from major medical databases, including PubMed and Scopus, using keywords such as "COVID-19", "pulmonary comorbidities", "long COVID", and "respiratory sequelae". Peer-reviewed articles published from January 2020 to the present were included, with data extracted to evaluate both the acute and long-term effects of these comorbidities on COVID-19 patients. Results: Patients with COPD demonstrated significantly higher risks of severe COVID-19, including increased hospitalization and mortality. Asthma, while less consistently associated with severe outcomes, showed a variable risk based on disease control. ILDs were strongly correlated with poor outcomes, including higher rates of respiratory failure and mortality. Long-term complications, such as persistent dyspnea, impaired lung function, and structural changes like fibrosis, were prevalent in patients recovering from moderate to severe COVID-19. These complications adversely affected quality of life and increased healthcare dependency. Conclusions: Pulmonary comorbidities amplify both the acute severity and long-term respiratory consequences of COVID-19. Effective management necessitates tailored strategies addressing both phases, integrating rehabilitation and continuous monitoring to mitigate chronic impairments. Future research should prioritize understanding the mechanisms behind these interactions to inform public health interventions and improve patient outcomes.}, } @article {pmid40094666, year = {2025}, author = {Nakamura, K and Kondo, K and Oka, N and Yamakawa, K and Ie, K and Goto, T and Fujitani, S}, title = {Donepezil for Fatigue and Psychological Symptoms in Post-COVID-19 Condition: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {8}, number = {3}, pages = {e250728}, doi = {10.1001/jamanetworkopen.2025.0728}, pmid = {40094666}, issn = {2574-3805}, mesh = {Humans ; *Donepezil/therapeutic use ; Female ; Male ; *Fatigue/drug therapy/etiology ; Double-Blind Method ; Middle Aged ; *Cholinesterase Inhibitors/therapeutic use ; *COVID-19/psychology/complications ; Japan ; SARS-CoV-2 ; Adult ; Aged ; COVID-19 Drug Treatment ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; Depression/drug therapy/etiology ; }, abstract = {IMPORTANCE: Fatigue is the most commonly reported symptom of post-COVID-19 condition (also known as long COVID) and impairs various functions. One of the underlying mechanisms may be intracerebral inflammation due to decreases in acetylcholine levels.

OBJECTIVE: To examine the effects of donepezil hydrochloride, an acetylcholinesterase inhibitor, on post-COVID-19 fatigue and psychological symptoms.

A multicenter, double-blind randomized clinical trial was performed in Japan. Between December 14, 2022, and March 31, 2024, adult patients within 52 weeks of the onset of COVID-19 and with a global binary fatigue score of 4 or greater on the Chalder Fatigue Scale were randomized into a donepezil or a placebo group.

EXPOSURE: The intervention was conducted during a 3-week period, with donepezil hydrochloride being administered at a dosage of 3 mg/d for the first week and then 5 mg/d for 2 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was a change in the Chalder Fatigue Scale score and the absolute score 3 weeks after the initiation of treatment. Other outcomes at 3 and 8 weeks, such as psychological symptoms and quality of life, were evaluated as secondary outcomes.

RESULTS: A total of 120 eligible patients were enrolled and 10 withdrew or were lost to follow-up; therefore, 110 patients (55 in each group) were included in the efficacy analysis (64 [58%] female; mean [SD] age, 43 [12] years). No significant differences were observed in baseline characteristics between the 2 groups. The baseline-adjusted estimating treatment effect of donepezil, measured as the mean difference on Chalder Fatigue Scale scores at 3 weeks, was 0.34 (95% CI, -2.23 to 2.91), showing no significant effect of the intervention (P = .79). Scores for the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, EuroQol 5-Dimension 5-Level Version, Patient Health Questionnaire, and Daily Health Status at 3 and 8 weeks were similar. No serious adverse events occurred in either group.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of donepezil to treat post-COVID-19 condition, the efficacy for fatigue and psychological symptoms was not confirmed in a general population. The development of effective therapeutics for post-COVID-19 symptoms is needed, and more clinical trials should be conducted in the future.

TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCT 2031220510.}, } @article {pmid40094121, year = {2025}, author = {Selvakumar, J and Havdal, LB and Brodwall, EM and Sommen, S and Berven, LL and Stiansen-Sonerud, T and Cvejic, E and Wyller, VBB}, title = {Risk factors for fatigue severity in the post-COVID-19 condition: A prospective controlled cohort study of nonhospitalised adolescents and young adults.}, journal = {Brain, behavior, & immunity - health}, volume = {44}, number = {}, pages = {100967}, pmid = {40094121}, issn = {2666-3546}, abstract = {Long COVID is a global health concern, leading to persistent symptoms and disability long after the acute SARS-CoV-2 infection in most age groups. The condition can manifest even following mild COVID-19, and in young people, it may have serious adverse consequences for educational attainment and transition to adulthood. Fatigue is the most prevalent symptom, but the underlying mechanisms remain poorly understood. In this prospective study of 404 SARS-CoV-2-positive and 105 SARS-CoV-2 negative, non-hospitalised youth (ages 12-25, female 62%), we investigated which factors in the early convalescent stage (<28 days since test) were associated with the severity of persistent fatigue at 6 months after infection. Participants completed questionnaires regarding clinical symptoms, social factors and psychological traits, and were subject to clinical and functional testing and biomarker analyses. Variables with significant (p < 0.2) associations to the outcome in simple linear regression were chosen for multivariable modelling, together with potential confounders. In the final multivariable model, SARS-CoV-2-positivity was a minor risk factor for fatigue severity at six months. Baseline severity of symptoms was the main risk factor and correlated with psychosocial factors such as loneliness and neuroticism, rather than biomarkers. Our results suggest that factors not related to infection are major risk factors for persistent fatigue in this age group.}, } @article {pmid40093756, year = {2025}, author = {Sanger, BD and Alarachi, A and McNeely, HE and McKinnon, MC and McCabe, RE}, title = {Brain Fog and Cognitive Dysfunction in Posttraumatic Stress Disorder: An Evidence-Based Review.}, journal = {Psychology research and behavior management}, volume = {18}, number = {}, pages = {589-606}, pmid = {40093756}, issn = {1179-1578}, abstract = {The term "brain fog" has long been used both colloquially and in research literature in reference to various neurocognitive phenomenon that detract from cognitive efficiency. We define "brain fog" as the subjective experience of cognitive difficulties, in keeping with the most common colloquial and research use of the term. While a recent increase in use of this term has largely been in the context of the post-coronavirus-19 condition known as long COVID, "brain fog" has also been discussed in relation to several other conditions including mental health conditions such as post-traumatic stress disorder (PTSD). PTSD is associated with both subjective cognitive complaints and relative deficits on cognitive testing, but the phenomenology and mechanisms contributing to "brain fog" in this population are poorly understood. PTSD psychopathology across cognitive, affective and physiological symptom domains have been tied to "brain fog". Furthermore, dissociative symptoms common in PTSD also contribute to the experience of "brain fog". Comorbid physical and mental health conditions may also increase the risk of experiencing "brain fog" among individuals with PTSD. Considerations for the assessment of "brain fog" in PTSD as part of psychodiagnostic assessment are discussed. While standard psychological intervention for PTSD is associated with a reduction in subjective cognitive deficits, other cognitive interventions may be valuable when "brain fog" persists following PTSD remission or when "brain fog" interferes with treatment. Limitations of current research on "brain fog" in PTSD include a lack of consistent definition and operationalization of "brain fog" in the literature, as well as limited tools for measurement. Future research should address these limitations, as well as further evaluate the use of cognitive remediation as an intervention for "brain fog".}, } @article {pmid40093251, year = {2025}, author = {Maguire, C and Kashyap, K and Williams, E and Aziz, R and Schuler, M and Ahamed, C and Wang, C and Mena, A and Saniuk, J and Busch, J and Austin, S and Kelley, M and Brode, WM and Melamed, E}, title = {Analysis of 977 Long COVID Patients Reveals Prevalent Neuropathy and Association with Anti-Ganglioside Antibodies.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.04.25323101}, pmid = {40093251}, abstract = {BACKGROUND: Long COVID (LC) is a novel condition that is characterized by persistent symptoms that last from months to years following a SARS-CoV-2 infection. While LC symptoms vary widely, neuropathy is one of the most prevalent symptoms and drastically affects patients' quality of life. However, the underlying pathophysiology of LC neuropathy remains poorly understood. Here, we investigated the prevalence and potential mechanisms of LC neuropathy in the largest LC neuropathy cohort to date.

METHODS: We conducted an observational study of 977 adults with LC at Dell Medical School. Participants underwent clinical assessments, skin punch biopsy, and comprehensive metabolic, endocrine and immunological profiling. A subset of patients received treatment with intravenous immunoglobulin (IVIG).

FINDINGS: Neuropathic symptoms were reported by 55% (534/977) participants, with skin biopsy confirming small fiber neuropathy in 56.5% (48/85) cases, affecting both epidermal and autonomic nerve fibers. Common risk factors for neuropathy, including metabolic and endocrine disorders, did not fully explain neuropathic symptoms. While general immunological markers (lymphocyte, T cell, and B cell count and C reactive protein were unremarkable, unexpectedly, we detected anti-ganglioside antibodies (AGAs) in 25% of patients with LC neuropathy, a comparable rate to other AGA-associated neuropathies. Longitudinal testing revealed persistent AGA positivity, and multiple elevated AGAs in a subset of patients. In a pilot treatment cohort of eight patients, IVIG treatment resulted in improvement of patient reported neuropathic symptoms.

INTERPRETATION: Our findings reveal a high prevalence of small fiber neuropathy in LC, with evidence suggesting an autoimmune mechanism involving AGAs in one in four LC neuropathy patients. The therapeutic response to IVIG further supports an autoimmune pathophysiology, suggesting potential benefits of immunomodulation in LC neuropathy patients.}, } @article {pmid40093216, year = {2025}, author = {Petrova, B and Syphurs, C and Culhane, AJ and Chen, J and Chen, E and Cotsapas, C and Esserman, D and Montgomery, R and Kleinstein, S and Smolen, K and Mendez, K and , and Lasky-Su, J and Steen, H and Levy, O and Diray-Arce, J and Kanarek, N}, title = {An Allele of the MTHFR one-carbon metabolism gene predicts severity of COVID-19.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.28.25323089}, pmid = {40093216}, abstract = {While the public health burden of SARS-CoV-2 infection has lessened due to natural and vaccine-acquired immunity, the emergence of less virulent variants, and antiviral medications, COVID-19 continues to take a significant toll. There are > 10,000 new hospitalizations per week in the U.S., many of whom develop post-acute sequelae of SARS-CoV-2 (PASC), or "long COVID", with long-term health issues and compromised quality of life. Early identification of individuals at high risk of severe COVID-19 is key for monitoring and supporting respiratory status and improving outcomes. Therefore, precision tools for early detection of patients at high risk of severe disease can reduce morbidity and mortality. Here we report an untargeted and longitudinal metabolomic study of plasma derived from adult patients with COVID-19. One-carbon metabolism, a pathway previously shown as critical for viral propagation and disease progression, and a potential target for COVID-19 treatment, scored strongly as differentially abundant in patients with severe COVID-19. A follow-up targeted metabolite profiling revealed that one arm of the one-carbon metabolism pathway, the methionine cycle, is a major driver of the metabolic profile associated with disease severity. The methionine cycle produces S-adenosylmethionine (SAM), the methyl group donor important for methylation of DNA, RNA, and proteins, and its high abundance was reported to correlate with disease severity. Further, genomic data from the profiled patients revealed a genetic contributor to methionine metabolism and identified the C677T allele of the MTHFR gene as a pre-existing predictor of disease trajectory - patients homozygous for the MTHFR C677T have higher incidence of experiencing severe disease. Our results raise the possibility that screening for the common genetic MTHFR variant may be an actionable approach to stratify risk of COVID severity and may inform novel precision COVID-19 treatment strategies.}, } @article {pmid40091647, year = {2025}, author = {Petker, S and Ogden, J}, title = {Patients' experiences of living with Long Covid and their beliefs about the role of psychology in their condition.}, journal = {Journal of health psychology}, volume = {}, number = {}, pages = {13591053251325112}, doi = {10.1177/13591053251325112}, pmid = {40091647}, issn = {1461-7277}, abstract = {Some patients with chronic conditions are unreceptive to a psychological approach. This study aimed to explore the experience of Long Covid (LC) with an emphasis on patients' beliefs about the role of psychology. UK participants (n = 14) with either self-reported or diagnosed LC took part in semi-structured interviews. Thematic analysis described three main themes: 'Living in uncertainty', 'Why should I trust you if you don't believe me?' and 'Once I know the cause people will believe me'. Transcending these themes was a tension between professional experts and experts by lived experience and a dichotomy between psychological and medical explanations. Overarching all themes was a sense that synthesising the biological and psychological components of LC could help to resolve this tension. In summary. living with LC is characterised by feeling disbelieved which can drive the rejection of psychology. Helping patients feel listened to may encourage a more positive approach to psychological support.}, } @article {pmid40090177, year = {2025}, author = {Kodama, S and Konishi, N and Hirai, Y and Fujisawa, A and Nakata, M and Teramukai, S and Fukushima, M}, title = {Efficacy of vitamin D replacement therapy on 28 cases of myalgic encephalomyelitis/chronic fatigue syndrome after COVID-19 vaccination.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {134}, number = {}, pages = {112718}, doi = {10.1016/j.nut.2025.112718}, pmid = {40090177}, issn = {1873-1244}, abstract = {BACKGROUND: Prolonged symptoms have been reported following both COVID-19 infection and vaccination, with some cases leading to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Of 80 patients presenting to our hospital with postvaccination syndrome, 28 met the diagnostic criteria for ME/CFS. We conducted a retrospective study on these 28 patients.

METHODS: We measured serum 25-hydroxyvitamin D levels in 28 patients who developed ME/CFS after COVID-19 vaccination between August 2022 and February 2024. Vitamin D replacement therapy included dietary counseling, sun exposure recommendations, and oral vitamin D supplementation. We evaluated changes in blood vitamin D levels and symptom improvement.

RESULTS: At initial visit, 27 of 28 patients diagnosed with ME/CFS had insufficient or deficient serum 25-hydroxyvitamin D levels (16 ± 4 ng/mL, mean ± SD). Following vitamin D replacement therapy, we observed an increase in blood vitamin D levels (28 ± 5 ng/mL) associated with a decrease in ME/CFS diagnostic symptoms (from 10.3 ± 2.1 to 3.3 ± 2.0). Notably, 23 of 28 patients (82%) no longer met ME/CFS diagnostic criteria after the therapy. Among the symptoms, sleep problems showed the most improvement (71%), followed by autonomic symptoms (68%).

CONCLUSIONS: For patients developing ME/CFS after COVID-19 vaccination with insufficient or deficient vitamin D levels, appropriate vitamin D replacement therapy under medical guidance may lead to symptomatic relief. We are preparing a randomized controlled trial to evaluate the efficacy of vitamin D replacement therapy in individuals with ME/CFS who have developed vitamin D deficiency following COVID-19 infection or vaccination.}, } @article {pmid40090175, year = {2025}, author = {Burton, C and Dawes, H and Dalton, C}, title = {Within person predictors of physical activity and fatigue in long Covid: Findings from an ecological momentary assessment study.}, journal = {Journal of psychosomatic research}, volume = {192}, number = {}, pages = {112091}, doi = {10.1016/j.jpsychores.2025.112091}, pmid = {40090175}, issn = {1879-1360}, abstract = {OBJECTIVE: We aimed to examine the extent to which current perceived demand for energy and affect predict subsequent physical activity and fatigue in people with Long Covid using an intensive longitudinal method (ecological momentary assessment).

METHODS: Analysis of data from a study of 69 adults with self-reported Long Covid combining 3-hourly self-report data perceived energy, and fatigue, on a smartphone app with continuous physical activity recording. We tested three hypotheses derived from cognitive behavioural and neuroscientific models of fatigue. These related to expectation, current affect and recalled emotional demand. Analysis used linear mixed effects models with fatigue and physical activity as outcomes.

RESULTS: Expectation of energy need for the next 3 h was predictive of physical activity, fatigue and recalled demandingness of the period. (p-values 0.005 to <0.0001). Currently feeling positive was predictive of slightly more subsequent physical activity and less fatigue 3 h later (p = 0.01). Feeling negative was not predictive of physical activity or subsequent fatigue but was predictive of subsequent recall of the period being emotionally demanding. Feeling more anxious was predictive of greater fatigue 3 h later (p = 0.001) but not of reduced physical activity. Absolute effects were small: a one-point increase in anticipated demand (on a scale of 1-7) was associated with an extra 2.2 min of moderate or vigorous physical activity and a one standard deviation increase in anxiety was associated with a one-point increase in fatigue (0-100 scale).

CONCLUSION: In the day-to-day experience of Long Covid expectation and affect have little detectable effect on subsequent physical activity or fatigue.}, } @article {pmid40088612, year = {2025}, author = {van der Knaap, N and Klinkhammer, S and Postma, AA and Visser-Meily, JMA and Horn, J and van Heugten, CM and Voorter, PHM and van der Thiel, MM and Drenthen, GS and Backes, WH and van Rosmalen, F and van Santen, S and van Bussel, BCT and van der Horst, ICC and Linden, DEJ and Ariës, MJH and Jansen, JFA}, title = {Post-COVID microvascular dysfunction in hospitalized COVID-19 survivors is associated with acute disease severity and persistent cognitive complaints.}, journal = {Journal of the neurological sciences}, volume = {472}, number = {}, pages = {123464}, doi = {10.1016/j.jns.2025.123464}, pmid = {40088612}, issn = {1878-5883}, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) is known to have adverse effects on the brain's vasculature in some patients. After recovery of the infection, vascular abnormalities may persist, but it remains unclear which pathological pathways play a role in post-COVID vascular and cognitive dysfunction and may contribute to post-COVID cognitive complaints.

METHODS: In this observational cohort study, 108 previously hospitalized COVID-19 survivors (general ward: n = 53; intensive care unit (ICU): n = 55) were compared. Cerebral microvascular properties in the cortical gray matter (cGM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH) were assessed using multi-b-value diffusion MRI around 9 months post-infection and related to acute systemic blood markers and post-COVID cognitive performance and complaints.

RESULTS: A lower microvascular perfusion volume fraction (fmv) and blood flow-related measure (fmv·Dmv) were found in ICU compared to general ward patients in the cGM (p = .032; p = .021), NAWM (p = .008; p = .006), and WMH (p = .014; p = .035). No associations were found between diffusion/perfusion metrics and cognitive performance, but a lower fmv in the NAWM was found in those with more cognitive complaints (p = .047). In ICU survivors, higher median blood lactate levels during ICU admission were associated with lower fmv (p = .031) and fmv·Dmv (p = .044) in the NAWM.

INTERPRETATION: Significantly more widespread post-COVID cerebral microvascular dysfunction was found in COVID-19 ICU compared to general ward survivors. Post-COVID microvascular dysfunction in the NAWM may be due to more severe cerebral tissue hypoxia at time of the infection and is associated with persisting subjective cognitive complaints, even in absence of objective cognitive problems.}, } @article {pmid40086694, year = {2025}, author = {Gourishankar, A}, title = {Geographic Disparities and Emerging Hotspot Trends of Long COVID in the United States.}, journal = {The American journal of the medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjms.2025.03.005}, pmid = {40086694}, issn = {1538-2990}, abstract = {OBJECTIVES: To study the emerging hotspot pattern of Long COVID (LC) in the U.S. population and investigate the correlation between Long COVID and state health system performance.

METHODS: Using 2022 to 2024 Center for Disease Control and Prevention adult LC data, I applied the Getis-Ord Gi* statistic with the Mann-Kendall trend test to determine emerging temporal trends associated with local clustering patterns across the contiguous states. A Pearson's correlation tested LC rates and state health system performance.

RESULTS: A spatiotemporal trend map described discrete patterns. In 2023, Long COVID rates were highest in Southeastern states such as Mississippi and West Virginia, but by 2024, mixed patterns were observed in some states. The LC rates showed an inverse relationship with state health outcome scores (r = -0.69, P < 0.001). Emerging hotspot analysis identified Mississippi as a persistent hotspot for Long COVID. Northeastern states showed consistently persistent cold spots.

CONCLUSIONS: The states with better health outcomes showed a lower frequency of long COVID. The geographically emerging hot spots can guide focused intervention and resource allocation for these patients.}, } @article {pmid39531735, year = {2025}, author = {Mak, J and Khan, S and Britton, A and Rose, S and Gwynn, L and Ellingson, KD and Meece, J and Feldstein, LR and Tyner, H and Edwards, LJ and Thiese, MS and Naleway, A and Gaglani, M and Solle, N and Burgess, JL and Lamberte, JM and Shea, M and Hunt-Smith, T and Caban-Martinez, A and Porter, C and Wiegand, R and Rai, R and Hegmann, KT and Hollister, J and Fowlkes, A and Wesley, M and Philips, AL and Rivers, P and Bloodworth, R and Newes-Adeyi, G and Olsho, LEW and Yoon, SK and Saydah, S and Lutrick, K}, title = {Association of Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination and Reductions in Post COVID Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in a US Prospective Cohort of Essential Workers.}, journal = {The Journal of infectious diseases}, volume = {231}, number = {3}, pages = {665-676}, doi = {10.1093/infdis/jiae556}, pmid = {39531735}, issn = {1537-6613}, support = {/IP/NCIRD CDC HHS/United States ; 75D30120R68013/CC/CDC HHS/United States ; 75D30120C08379/CC/CDC HHS/United States ; 75D30120C08150/CC/CDC HHS/United States ; //Abt Associates, Inc)/ ; }, mesh = {Humans ; *COVID-19/prevention & control/epidemiology/virology ; Male ; *COVID-19 Vaccines/administration & dosage/immunology ; Female ; Middle Aged ; Adult ; *SARS-CoV-2/immunology ; Case-Control Studies ; Prospective Studies ; *Vaccination ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BACKGROUND: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

METHODS: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression.

RESULTS: Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16-.85], 0.56 [.32-.97], and 0.48 [.25-.91], respectively).

CONCLUSIONS: COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.}, } @article {pmid40084919, year = {2025}, author = {Baalbaki, N and Slob, EMA and Kazer, SW and I Abdel-Aziz, M and Bogaard, HJ and Golebski, K and Maitland-van der Zee, AH}, title = {The Omics Landscape of Long COVID-A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16526}, pmid = {40084919}, issn = {1398-9995}, support = {//Health~Holland/ ; }, abstract = {An estimated 10% of coronavirus disease (COVID-19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom-based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full-text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood-brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial-derived metabolite production and persistent inflammation. Limitations include cross-study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics-integrated studies to advance the development of biomarkers and targeted treatments.}, } @article {pmid40084807, year = {2025}, author = {Tang, CC and Wu, WW and Ho, SJ and Liu, WD and Pan, MY and Chang, SC and Wang, WS and Yeh, YC and Chen, CH and Chang, JC}, title = {Clinically Significant Functional Impairments and Symptoms in COVID-19 Survivors: Empirical Research Quantitative.}, journal = {Journal of clinical nursing}, volume = {}, number = {}, pages = {}, doi = {10.1111/jocn.17715}, pmid = {40084807}, issn = {1365-2702}, support = {//Collaborative Research Projects of National Taiwan University College of Medicine/ ; //National Taiwan University Hospital/ ; 109F005-110-P//Min-Sheng General Hospital/ ; }, abstract = {BACKGROUND: COVID-19 survivors may experience complex, distressing and persistent symptoms, referred to as long COVID, lasting months or years after diagnosis. More evidence is needed for effective long COVID screening and management.

AIM: To explore the clinical profile of long COVID and factors associated with its development.

DESIGN: A multicentre correlational study using a cross-sectional design.

METHODS: Adults diagnosed with COVID-19 6-9 months earlier were recruited via social media and referrals from three facilities. Participants provided demographic data and assessed their symptoms and functional status using validated questionnaires. Data were analysed using descriptive statistics and binomial logistic regression.

RESULTS: Among 102 participants, 13%-30% reported significant impairments in cognitive, emotional and physical functioning. Over 10% experienced symptoms such as diarrhoea, sleep problems, dyspnoea, nausea, fatigue and pain. These impairments and symptoms were associated with acute symptom severity, chronic disease, overweight status, regular exercise and living without partners.

CONCLUSION: This study adds to the literature by examining long-term functional status and symptoms in omicron survivors using comprehensive, validated tools. The findings highlight the prevalence and clinical significance of long COVID symptoms, aiding in the identification of functional impairments requiring medical and nursing interventions.

Nurses should recognise these symptoms and educate survivors about potential challenges. Policies addressing long-term issues, including research, health services and education, are essential.

REPORTING METHOD: This study follows the STROBE guideline (Table S1).

Patients self-reported symptoms for this study.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT05303103).}, } @article {pmid40084715, year = {2025}, author = {Afroze, F and Arafat, SM and Ahmed, CM and Alam, B and Banu, S and Islam, MZ and Mahfuz, M and Qadri, F and Bhuiyan, TR and Parvin, I and Ackhter, MM and Islam, F and Sultana, M and Sultana, E and Rahaman, MFU and Khan, AH and Hasan, MN and Ahmed, S and Chisti, MJ and Ahmed, T}, title = {Evolution of long COVID over two years in hospitalised and non-hospitalised survivors in Bangladesh: a longitudinal cohort study.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04075}, pmid = {40084715}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology ; Bangladesh/epidemiology ; Longitudinal Studies ; Male ; Female ; *Survivors/statistics & numerical data ; *Hospitalization/statistics & numerical data ; Middle Aged ; Adult ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Incidence ; }, abstract = {BACKGROUND: In developing settings, comparative data on COVID hospitalised survivors (HS) and non-hospitalised survivors (NHS) is scarce. We determined burdens, incidence, evolution, and associated factors of long COVID-19 over two years among these groups.

METHODS: We conducted a longitudinal cohort study in Dhaka, Bangladesh, and recruited confirmed COVID-19 survivors from December 2020 to May 2021 (previously reported). 346 survivors underwent in-person follow-ups at five, nine, 18 months and two years post-infection. The assessment included long COVID symptoms, cardiorespiratory function, neuropsychiatric conditions, quality of life, and laboratory tests. The outcomes included one or more symptoms and/or signs indicative of long COVID, aligning closely with the World Health Organization definition of post-COVID-19 condition.

RESULTS: Of the 346 participants, we included 326 in the analysis. 78% of HS (n/N = 171/219) and 62% of NHS (n/N = 55/89) reported at least one sequela symptom. HS had higher odds of palpitations, headaches, dizziness, sleeping difficulties, brain fog, muscle weakness, joint pain, hypertension, insulin requirement, poor quality of life, and prolonged corrected QT intervals on electrocardiogram compared to NHS at two years (95% confidence interval (CI)>1). Regarding evolution, sequelae-symptoms, neurological outcomes, restrictive spirometry findings, and electrocardiogram abnormalities remained unchanged, although psychiatric sequelae, quality of life, and exercise capacity improved in both groups. Hospital readmission rates significantly increased (P < 0.05). The incidence rates of palpitations, cough, and hypertension were higher in HS compared to NHS (95% CI>1). Two or more vaccine doses decreased the risk of respiratory (adjusted risk ratio (aRR) = 0.76; 95% CI = 0.63-0.91) and psychiatric sequelae (aRR = 0.78; 95% CI = 0.66-0.92) than one or no doses.

CONCLUSIONS: COVID-19 survivors, particularly HS, experienced a higher burden of persistent symptoms and health issues two years after infection. However, vaccination significantly reduced the risk of respiratory and psychiatric outcomes. These findings highlight the importance of ongoing vaccination programs and the need for targeted rehabilitation services in low-resource settings.}, } @article {pmid40084630, year = {2025}, author = {Bobak, L and Dorney, I and Kovacevich, A and Barnett, BS}, title = {Therapeutic Potential of Psilocybin for Treating Neuropsychiatric Long COVID Symptoms: A Reddit Investigation.}, journal = {Journal of psychoactive drugs}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/02791072.2025.2478097}, pmid = {40084630}, issn = {2159-9777}, abstract = {Long COVID lacks effective pharmaceutical treatment options. Psychedelic treatment for long COVID has received attention given anecdotal reports of neuropsychiatric symptom improvement. This study investigates the use of psilocybin for neuropsychiatric long COVID symptoms, examining online accounts of individuals with reported long COVID using psilocybin. We searched the Reddit communities, "r/LongCovid," and "r/covidlonghaulers" for terms, "psilocybin," "shrooms," and "magic mushrooms." Posts were included if they self-reported (1) neuropsychiatric symptoms of long COVID, (2) use of psilocybin, and (3) descriptions of the perceived effect or lack thereof on long COVID symptoms. Posts were manually coded to identify the nature of psilocybin ingestion, long COVID symptoms, and post's author's perceived effect on symptoms. The most common symptoms identified were fatigue (47.3%, N = 52), cognitive impairment (46.4%, N = 51), and depression (30.0%, N = 33). Of 110 posts meeting criteria, 78.2% (N = 86) reported any improvement in long COVID symptoms, while 11.8% (N = 13) reported worsening. For those with improvement, 77.9% (N = 67) reported improvement lasting beyond their acute psychedelic experience, while 5.8% (N = 5) reported improvement only during the experience. Given these findings, studies employing comparison social media data for other long COVID self-treatments and/or prospective observational studies of individuals self-treating neuropsychiatric long COVID symptoms with psychedelics may be warranted.}, } @article {pmid40084453, year = {2025}, author = {Serafini, A and Shaughnessy, AF}, title = {[The only effective treatments for long Covid are cognitive behavioral therapy and integrated physical and mental health rehabilitation.].}, journal = {Recenti progressi in medicina}, volume = {116}, number = {3}, pages = {195-196}, doi = {10.1701/4460.44563}, pmid = {40084453}, issn = {2038-1840}, } @article {pmid40084175, year = {2025}, author = {Prazeres, F and Romualdo, AP and Campos Pinto, I and Silva, J and Oliveira, AM}, title = {The impact of long COVID on quality of life and work performance among healthcare workers in Portugal.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e19089}, pmid = {40084175}, issn = {2167-8359}, mesh = {Humans ; *Quality of Life/psychology ; Portugal/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Health Personnel/psychology/statistics & numerical data ; *COVID-19/psychology/epidemiology ; Adult ; *Work Performance ; Middle Aged ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is a multisystem infectious disease which affected 5.7 million people in Portugal. A subgroup of patients experienced long-term effects from the infection, now referred to as long COVID. Long COVID can considerably reduce the quality of life (QoL) of affected patients. This study aimed to evaluate the impact of long COVID on QoL and work performance among healthcare workers (HCWs) in Portugal.

METHODS: A cross-sectional correlational survey was performed in 348 HCWs employed either in hospitals, or non-hospital health facilities in Portugal. Participants completed an online survey using Google Forms between May and June 2024, which consisted of multiple-choice questions and took less than 10 min to fill out. Long COVID was considered present if the defined symptoms started at least 3 months after the primary infection of COVID-19, and persisted for at least 2 months. The outcome measures were performance at work and QoL. Performance at work was measured using a seven-point Likert scale and QoL was evaluated using the Satisfaction with Life Scale (SWLS). Data was analyzed using SPSS.

RESULTS: A total of 277 participants (79.6%) had history of SARS-CoV-2 infection, and 223 participants (64.1%) reported a history of long COVID. Extreme fatigue was reported by 158 participants (57.0%), cognitive dysfunction by 118 participants (42.6%), shortness of breath by 76 participants (27.4%), and persistent cough by 168 participants (60.6%). In the multivariate analysis, long COVID was significantly associated with lower SWLS scores indicating that long COVID negatively impacted QoL. Having two or more chronic diseases showed a trend towards lower performance, and extreme fatigue and cognitive dysfunction showed strong negative associations with performance.

DISCUSSION: Based on a national sample of HCWs (348 individuals), a high percentage of participants (64.1%) reported a history of long COVID. These results suggest that HCWs in Portugal have a prevalence of the disease similar to that of the worldwide population. Concerning performance at work, having two or more chronic diseases showed a trend towards lower performance, as well as extreme fatigue and cognitive dysfunction. Interestingly, we found a negative association between being a clinical secretary and SWLS. This might be explained by the specific challenges or stressors faced by clinical secretaries, which could negatively impact their QoL. In conclusion, long COVID was prevalent in the studied sample of HCWs and had a negative impact on their QoL. Extreme fatigue and cognitive dysfunction were strongly negatively associated with performance. This suggests the need for targeted care for HCWs as a group. The results of this study can guide healthcare authorities in addressing important long-term consequences that should be considered in rehabilitation programs for post-COVID-19 recovery.}, } @article {pmid40083183, year = {2025}, author = {Cheung, CCL and Mok, CC}, title = {Long COVID in patients with systemic lupus erythematosus: A case-control study.}, journal = {Lupus}, volume = {}, number = {}, pages = {9612033251326987}, doi = {10.1177/09612033251326987}, pmid = {40083183}, issn = {1477-0962}, abstract = {BackgroundLong COVID was defined by the WHO as continuation or development of new symptoms 3 months after the initial SARS-CoV2 infection, with these symptoms lasting for ≥2 months without alternative explanations.ObjectivesTo compare the incidence of long COVID in patients with SLE with matched controls after a SARS-CoV2 infection.MethodsConsecutive patients (≥18 years) who fulfilled the ACR or SLICC criteria for SLE between July to November 2023 were recruited. Those with SARS-CoV2 infection (positive rapid antigen test [RAT] or PCR) were identified by a self-reported questionnaire, which also captured the duration and severity of a number of pre-defined symptoms of long COVID. An equal number of healthy subjects, matched for gender and age, who had SARS-CoV2 infection in the same period were recruited for the same survey. The incidence and presentation of long COVID was compared between patients and controls, and risk factors for long COVID in SLE patients were studied.ResultsA total of 211 SLE patients (97.6% women, age 44.2 ± 11.9 years) and 211 healthy controls (97.6% women, age 44.2 ± 11.9 years) were studied. In all patients, the most common long COVID symptoms were fatigue (30.1%), worsening of memory (29.1%), difficulty to concentrate (26.3%), cough (23.2%) and insomnia (18.9%). Compared with controls, the incidence of long COVID was significantly higher in SLE patients (54.5% vs 34.6%; OR 2.27 [1.53-3.35]). Symptoms of worsening of memory (OR 2.77 [1.78-4.31]), chest pain (OR 4.18 [1.16-15.0]), palpitation (OR 3.43 [1.58-7.47]) and arthralgia (OR 2.67 [1.29-5.53]) were significantly more common in SLE patients than controls. However, no clinical and serological factors were significantly associated with the occurrence of long COVID in SLE patients except the ever use of hydroxychloroquine (OR 2.03 [1.04-3.96]).ConclusionsLong COVID is more common in SLE patients than matched controls after a SARS-CoV2 infection. The development of long COVID symptoms in SLE is largely unpredictable.}, } @article {pmid40083165, year = {2025}, author = {Li, S and Dai, B and Hou, Y and Zhang, L and Liu, J and Hou, H and Song, D and Wang, S and Li, X and Zhao, H and Wang, W and Kang, J and Tan, W}, title = {Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251323482}, doi = {10.1177/17534666251323482}, pmid = {40083165}, issn = {1753-4666}, mesh = {Humans ; *COVID-19/rehabilitation/physiopathology ; *Randomized Controlled Trials as Topic ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Lung/physiopathology ; Treatment Outcome ; Exercise Tolerance ; Respiratory Function Tests ; Recovery of Function ; Male ; Middle Aged ; Female ; }, abstract = {BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.

OBJECTIVES: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES AND METHODS: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.

RESULTS: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.

CONCLUSION: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.

TRIAL REGISTRATION: PROSPERO ID: CRD42024455008.}, } @article {pmid40082863, year = {2025}, author = {Kogevinas, M and Karachaliou, M and Espinosa, A and Iraola-Guzmán, S and Castaño-Vinyals, G and Delgado-Ortiz, L and Farré, X and Blay, N and Pearce, N and de Basea, MB and Nogués, EA and Dobaño, C and Moncunill, G and de Cid, R and Garcia-Aymerich, J}, title = {Risk, determinants, and persistence of long-COVID in a population-based cohort study in Catalonia.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {140}, pmid = {40082863}, issn = {1741-7015}, support = {001-P-001647//European Regional Development Fund/ ; RYC 2020-029886-I/AEI/10.13039/501100011033//European Social Fund/ ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/epidemiology ; Adult ; *SARS-CoV-2 ; Spain/epidemiology ; Risk Factors ; Aged ; Prospective Studies ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; Immunoglobulin G/blood ; }, abstract = {BACKGROUND: Long-COVID has mostly been investigated in clinical settings. We aimed to assess the risk, subtypes, persistence, and determinants of long-COVID in a prospective population-based study of adults with a history of SARS-CoV-2 infection in Catalonia.

METHODS: We examined 2764 infected individuals from a population-based cohort (COVICAT) established before the pandemic and followed up three times across the pandemic (2020, 2021, 2023). We assessed immunoglobulin (Ig)G levels against SARS-CoV-2, clinical, vaccination, sociodemographic, and lifestyle factors. Long-COVID risk and subtypes were defined based on participant-reported symptoms and electronic health records. We identified a total of 647 long-COVID cases and compared them with 2117 infected individuals without the condition.

RESULTS: Between 2021 and 2023, 23% of infected subjects developed long-COVID symptoms. In 56% of long-COVID cases in 2021, symptoms persisted for 2 years. Long-COVID presented clinically in three subtypes, mild neuromuscular, mild respiratory, and severe multi-organ. The latter was associated with persistent long-COVID. Risk was higher among females, participants under 50 years, of low socioeconomic status, severe COVID-19 infection, elevated pre-vaccination IgG levels, obesity, and prior chronic disease, particularly asthma/chronic obstructive pulmonary disease and mental health conditions. A lower risk was associated to pre-infection vaccination, infection after omicron became the dominant variant, higher physical activity levels, and sleeping 6-8 h. Vaccination during the 3 months post-infection was also protective against long-COVID.

CONCLUSIONS: Long-COVID persisted for up to 2 years in half of the cases, and risk was influenced by multiple factors.}, } @article {pmid40080521, year = {2025}, author = {Turner, GM and Calvert, M and Foy, R and Atkins, L and Collis, P and Tearne, S and Jowett, S and Handley, K and Mant, J}, title = {Structured follow-up pathway to address unmet needs after transient ischaemic attack and minor stroke (SUPPORT TIA): Feasibility study and process evaluation.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0317425}, doi = {10.1371/journal.pone.0317425}, pmid = {40080521}, issn = {1932-6203}, mesh = {Humans ; *Ischemic Attack, Transient/therapy ; *Feasibility Studies ; Female ; Male ; Aged ; *Stroke/therapy ; Middle Aged ; Follow-Up Studies ; Patient Reported Outcome Measures ; Surveys and Questionnaires ; Aged, 80 and over ; }, abstract = {BACKGROUND: Care following transient ischaemic attack (TIA) and minor stroke is variable and often leaves patients feeling abandoned and uncertain. We developed a theoretically-informed, multifaceted intervention which comprised nurse-led, structured follow-up at 4 weeks after TIA/minor stroke to identify and address patient needs. This study evaluated the feasibility and acceptability of both the intervention and procedures to inform a future randomised controlled trial.

METHOD: We conducted a multicentre, randomised feasibility study with mixed-methods process evaluation (ISRCTN registry reference: ISRCTN39864003). We collected patient reported outcome measures (PROMs) at 1, 12 and 24 weeks and clinical data at baseline and 24 weeks. The process evaluation comprised qualitative interviews with a sub-sample, feedback questionnaires, and observations of intervention delivery.

RESULTS: We recruited 54 patients over 12 months, achieving 90% of the target sample size (n = 60). PROMs return rates were 94.4% (51/54), 85.2% (46/54) and 71.1% (27/38) at 1, 12, and 24-weeks, respectively. Intervention fidelity was high and the intervention largely aligned with the theoretical underpinnings. The process evaluation illustrated how patients benefitted from the intervention through support they would not have received through usual care. This included direct referral or signposting to support services, information and education, actionable advice, and reassurance about and normalisation of recovery. The trial design was feasible and acceptable for both patients and clinicians.

CONCLUSION: Nurse-led, structured follow-up after TIA and minor stroke is feasible, acceptable and valued by patients and clinicians. Our intervention can identify and help address unmet needs. A definitive randomised trial to evaluate intervention effectiveness and cost-effectiveness is feasible and acceptable.}, } @article {pmid40080079, year = {2025}, author = {Li, D and Long, F and Zhang, S and Yu, B}, title = {Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children.}, journal = {Physiology international}, volume = {}, number = {}, pages = {}, doi = {10.1556/2060.2025.00484}, pmid = {40080079}, issn = {2498-602X}, abstract = {OBJECTIVE: Although SARS-CoV-2 primarily targets the respiratory system, there is evidence that it can also infect the central nervous system, especially in children, leading to neurological symptoms and long-term consequences. It is imperative to summarize the possible mechanisms, main symptoms, and treatments of neurological symptoms of COVID-19 in children.

METHODS: We performed a literature search using the PubMed online database to find studies investigating the mechanisms of COVID-19 infection of the central nervous system and therapies for COVID-19 neurological symptoms in children.

RESULTS: The main mechanisms of action of SARS-CoV-2 virus on the nervous system are direct invasion, systemic inflammation and molecular mimicry. Although the incidence of adverse reactions to intravenous IgG therapy (IVIG) varies greatly and the contraindications are not yet clear, IVIG has been shown to be clearly effective for the neurological symptoms of COVID-19 in children.

CONCLUSION: However, due to insufficient data, more clinical studies are still needed to confirm its safety and efficacy, further improve the treatment plan, and determine the appropriate dosage to better serve clinical practice.

SIGNIFICANCE: The specific regimen of IVIG treatment for COVID-19 in children was explored, which further improved the understanding of COVID-19 and L-C19 neurological diseases in children.}, } @article {pmid40079963, year = {2025}, author = {Rudolph, AE and Al Akoury, N and Bogdanenko, N and Markus, K and Whittle, I and Wright, O and Haridy, H and Spinardi, JR and McLaughlin, JM and Kyaw, MH}, title = {Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A systematic literature review.}, journal = {Human vaccines & immunotherapeutics}, volume = {21}, number = {1}, pages = {2474772}, doi = {10.1080/21645515.2025.2474772}, pmid = {40079963}, issn = {2164-554X}, mesh = {Humans ; *COVID-19/prevention & control/immunology ; *COVID-19 Vaccines/administration & dosage/immunology ; *Vaccination/statistics & numerical data ; *SARS-CoV-2/immunology ; *Vaccine Efficacy ; Adult ; }, abstract = {This systematic literature review summarizes the evidence across 56 publications and pre-prints (January 2020-July 2023) with low-risk of bias based on JBI critical appraisal, that report adjusted estimates for the relationship between COVID-19 vaccination and Post-COVID-19 Condition (PCC) by timing of vaccination relative to infection or PCC-onset. Comparisons of adjusted vaccine effectiveness (aVE) against ≥1 PCC (vs. unvaccinated) across study characteristics known to impact PCC burden or VE against other COVID-19 endpoints were possible for 31 studies where vaccination preceded infection. Seventy-seven percent of pre-infection aVE estimates were statistically significant (range: 7%-95%). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%-84%) than non-mRNA vaccines (range: 16%-38%) and aVE ranges before and during Omicron overlapped. Our findings suggest that COVID-19 vaccination before SARS-CoV-2 infection reduces the risk of PCC regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.}, } @article {pmid40079454, year = {2025}, author = {Barrera Martínez, Y and Boillat Oriani, GA and Vega Montes, P and Martínez Moreno, E and Pérez Pérez, A and Casajuana Pérez, RJ and Muñoz Cobos, F}, title = {[Long-term persistence of post-COVID-19 symptoms: A two-year follow-up of a Primary Care cohort].}, journal = {Anales del sistema sanitario de Navarra}, volume = {48}, number = {1}, pages = {}, doi = {10.23938/ASSN.1101}, pmid = {40079454}, issn = {2340-3527}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; *Quality of Life ; Spain/epidemiology ; Adult ; Follow-Up Studies ; *Primary Health Care/statistics & numerical data ; Cohort Studies ; Time Factors ; Aged ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Prevalence ; Prognosis ; Fatigue/epidemiology/etiology ; }, abstract = {BACKGROUND: This study aims to determine the prevalence of long COVID two years after initial infection, identify prognostic factors, and assess its impact on quality of life.

METHODOLOGY: An ambispective cohort study was conducted with patients aged = 18 years from two health centers in Málaga, Spain, who tested positive for SARS-CoV-2 between October 2020 and May 2021. Systematic random sampling was performed in October 2022, with 5% precision, 5% alpha error, and 25% expected losses. The cohort was followed until May 2023. Dependent variables included long COVID (= 1 symptom lasting =8 weeks), symptom count, quality of life (EuroQol 5-D), and global health perception (EQ-EVA). Independent variables included age, sex, severity of initial infection severity, vaccination status, comorbidities, and reinfection.

RESULTS: Of 914 eligible individuals, 173 patients were sampled (mean age 47 years, 58.4% female). Long COVID was observed in 32.36% of participants, with 23% affected two years after infection. Fatigue and anosmia/dysgeusia were the most frequent symptoms. Prognostic factors for long COVID included higher initial infection severity, younger age, and reinfection. For symptom count, factors were depression, initial infection severity, and reinfection. Health perception was eight points lower in long COVID patients (77.72: SD=17.10 vs 86.15; SD=16.25; p<0.001). Female sex, older age, fewer comorbidities, and more vaccine doses were associated with better quality of life.

CONCLUSIONS: Thirty-two percent of patients experienced long COVID, mainly fatigue and anosmia/dysgeusia. It associates with higher initial severity, younger age, and reinfection, negatively impacting quality of life.}, } @article {pmid40077917, year = {2025}, author = {Cheaban, R and Rogge, AL and Schaeper, KE and Weinrautner, N and Kirschning, T and Bruenger, F and Serrano, MR and Rudloff, M and Barndt, I and Wiemer, M and Schramm, R and Gummert, JF and Guenther, SP}, title = {Post COVID symptom burden in patients supported with extracorporeal membrane oxygenation: A prospective 2-year follow-up analysis.}, journal = {The International journal of artificial organs}, volume = {}, number = {}, pages = {3913988251322710}, doi = {10.1177/03913988251322710}, pmid = {40077917}, issn = {1724-6040}, abstract = {OBJECTIVES: A systematic characterization of the long-term sequelae after the severest form of COVID-19 requiring ECMO-therapy is lacking. Here, we present 2-year follow-up data of COVID-19 ECMO survivors, and analyze the cardiopulmonary, neurocognitive, psychological, and functional status, plus health-related quality of life (HRQL).

METHODS: From 04/2020 to 09/2021, 60 COVID patients were supported with ECMO. Survival to discharge was 40.0% (n = 24), and 6-month survival was 33.3% (n = 20). Follow-ups were performed via phone and mail using validated tools. Six-month outcomes have been published before.

RESULTS: At 2 years, 20 patients were alive. N = 19 agreed to participate in this study (median age 57.0 (45.0-63.0) years, 21.1% female). The cardiopulmonary status was satisfactory (78.9% in NYHA level I-II). Altogether, 84.2% were vastly independent in daily life. However, 47.4% still showed cognitive impairment, 21.1% moderate, 15.8% severe depression, and 15.8% posttraumatic stress disorder symptoms. HRQL subscale results were similar to 6 months, but patients self-rated their overall health significantly better (70.0% (50.0%-80.0%) vs 50.0% (30.0%-80.0%), p = 0.04). The number of patients working was increasing. Social life remained markedly affected.

CONCLUSIONS: Two-year outcomes in COVID-19 ECMO patients were stable to improving as compared to 6-month results. However, long-term impairments affected all aspects of life. Long COVID specifically, and post ECMO sequelae in general need to be characterized further to enable maximum recovery.}, } @article {pmid40077880, year = {2025}, author = {Villatoro, C and Henning, E and Ng, R and Kogut, M and Steinberg, J and Chen, B and Holingue, C and Leppert, M and Malone, LA}, title = {Enhancing Pediatric Long COVID Care Through Telementoring: Insights From an ECHO Program.}, journal = {Clinical pediatrics}, volume = {}, number = {}, pages = {99228251323396}, doi = {10.1177/00099228251323396}, pmid = {40077880}, issn = {1938-2707}, abstract = {Long COVID affects a significant number of children, yet clinician knowledge gaps and limited access to specialized care hinder effective management. With fewer than 20 pediatric long COVID clinics in the United States, many families must travel long distances for care. To address these challenges, a pediatric long COVID ECHO (Extension for Community Healthcare Outcomes) program was developed to educate health care professionals on evidence-based care. The program engaged 94 participants from the United States and Canada via weekly tele-education sessions, recruited through word of mouth and professional listservs. Pre-surveys (41% response rate) and post-surveys (29% response rate) were sent to attendees. Participants reported statistically significant improvements in knowledge, confidence, competence, and self-efficacy (P < 0.001). This program represents a valuable initiative to facilitate timely interventions and empower primary care and community providers in diagnosing, treating, and managing long COVID in pediatric populations.}, } @article {pmid40076720, year = {2025}, author = {Fernández-de-Las-Peñas, C and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Torres-Macho, J and Ryan-Murua, P and Franco-Moreno, AI and Pellicer-Valero, OJ and Arendt-Nielsen, L and Giordano, R}, title = {DNA Salivary Methylation Levels of the ACE2 Promoter Are Not Related to ACE2 (rs2285666 and rs2074192), TMPRSS2 (rs12329760 and rs2070788) and ACE1 rs1799752 Polymorphisms in COVID-19 Survivors with Post-COVID-19 Condition.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, doi = {10.3390/ijms26052100}, pmid = {40076720}, issn = {1422-0067}, support = {NNF21OC0067235//Novo Nordisk Foundation/ ; THE LONG COVID EX CM//Comunidad de Madrid/ ; }, mesh = {Humans ; *COVID-19/genetics/virology ; *DNA Methylation ; Female ; *Angiotensin-Converting Enzyme 2/genetics ; Male ; *Promoter Regions, Genetic/genetics ; Middle Aged ; *Serine Endopeptidases/genetics ; *Polymorphism, Single Nucleotide ; Aged ; *Saliva/metabolism ; *SARS-CoV-2/genetics ; Adult ; Survivors ; Genotype ; Peptidyl-Dipeptidase A/genetics ; Epigenesis, Genetic ; }, abstract = {Genetics and epigenetics are mechanisms proposed for explaining post-COVID-19 condition. This secondary analysis aimed to investigate if DNA methylation levels of the ACE2 promoter are different depending on the genotype of five COVID-19-related polymorphisms in individuals who had been previously hospitalized due to SARS-CoV-2 infection. We collected non-stimulated saliva samples from 279 (48.7% female, age: 56.0 ± 12.5 years) previously hospitalized COVID-19 survivors. The participants self-reported for the presence of post-COVID symptomatology that started after the infection and persisted at the time of the appointment. Three potential genotypes of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, and ACE1 rs1799752 polymorphisms were identified from saliva samples. Further, methylation levels at five different locations (CpG) of dinucleotides in the ACE2 promoter were quantified using bisulfited pyrosequencing. Differences in the methylation percentage (%) of each CpG according to the genotype of the five polymorphisms were analyzed. Participants were evaluated up to 17.8 (SD: 5.2) months after hospital discharge. Eighty-eight percent (88.1%) of patients reported at least one post-COVID symptom (mean number of post-COVID symptoms: 3.0; SD: 1.9). Overall, we did not observe significant differences in the methylation levels of the ACE2 promoter according to the genotype of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, or ACE1 rs1799752 single nucleoid polymorphisms. This study did not find an association between genetics (genotypes of five COVID-19-associated polymorphisms) and epigenetics (methylation levels of the ACE2 promoter) in a cohort of COVID-19 survivors with post-COVID-19 condition who were hospitalized during the first wave of the pandemic.}, } @article {pmid40076527, year = {2025}, author = {Sun, DS and Lien, TS and Chang, HH}, title = {Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, doi = {10.3390/ijms26051898}, pmid = {40076527}, issn = {1422-0067}, support = {104-2320-B-320 -009 -MY3, 107-2311-B-320-002-MY3, 111-2320-B320-006-MY3, 112-2320-B-320-007//National Science and Technology Council, Taiwan/ ; TCMMP104-06, TCMMP108-04, TCMMP 111-01, TCAS111-02, TCAS-112-02, TCAS113-04, TCRD112-033, TCRD113-041//Tzu-Chi Medical Foundation/ ; }, mesh = {Humans ; *Severe Dengue/immunology/virology ; *COVID-19/immunology/virology ; *Dengue Virus/immunology ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology ; *Antibody-Dependent Enhancement/immunology ; Autoantibodies/immunology ; Post-Acute COVID-19 Syndrome ; Animals ; }, abstract = {Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.}, } @article {pmid40075382, year = {2025}, author = {Weigel, B and Inderyas, M and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S}, title = {Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {318}, pmid = {40075382}, issn = {1479-5876}, support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Buxton Foundation/ ; 4879//Henty Community/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic ; *Quality of Life ; *COVID-19/psychology/epidemiology ; SARS-CoV-2 ; Female ; }, abstract = {PURPOSE: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.

METHODS: CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).

RESULTS: This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.

CONCLUSION: ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.}, } @article {pmid40074801, year = {2025}, author = {Nishi, K and Yoshimoto, S and Tanaka, T and Kimura, S and Tsunoda, T and Watanabe, A and Teranaka, K and Oguma, Y and Ogawa, H and Kumai, T and Yamano, T}, title = {Spatial transcriptomics of the epipharynx in long COVID identifies SARS-CoV-2 signalling pathways and the therapeutic potential of epipharyngeal abrasive therapy.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8618}, pmid = {40074801}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/genetics/virology ; *SARS-CoV-2/physiology ; *Signal Transduction ; Transcriptome ; Male ; Female ; Middle Aged ; RNA, Viral/genetics ; Gene Expression Profiling ; Aged ; }, abstract = {In this study, the critical role of the epipharynx in managing long-term coronavirus disease 2019 (COVID-19), and in particular, how residual SARS-CoV-2 RNA affects signalling pathways in the epipharynx were investigated via spatial gene expression analysis (Visium HD). Moreover, we hypothesize that epipharyngeal abrasive therapy (EAT) targeting the epipharynx could improve long COVID symptoms by modulating local inflammation and gene expression. We conducted a comparative analysis of the gene expression profiles of three patients with long COVID and two control individuals without COVID-19. Residual SARS-CoV-2 RNA was detected in the epipharynx of patients with long COVID, along with the activation of signalling pathways in epithelial and immune cells. After EAT, the viral RNA was either completely cleared or significantly reduced. T-cell receptor signalling pathways were suppressed; the levels of proinflammatory cytokines, such as interleukin-6 and tumour necrosis factor-α, were reduced; and excessive antibody production was mitigated. Histology showed that EAT effectively eliminated the inflamed, dysfunctional ciliated epithelium. This study clarifies that SARS-CoV-2 has long-term effects on the immune response in the epipharynx, emphasizing the need to focus on chronic epipharyngitis as a potential cause of long COVID. Furthermore, EAT may offer a promising approach to alleviating persistent long COVID symptoms.}, } @article {pmid40074704, year = {2025}, author = {Schwartz, J and Capistrano, K and Hussein, H and Hafedi, A and Shukla, D and Naqvi, A}, title = {Oral SARS-CoV-2 Infection and Risk for Long Covid.}, journal = {Reviews in medical virology}, volume = {35}, number = {2}, pages = {e70029}, doi = {10.1002/rmv.70029}, pmid = {40074704}, issn = {1099-1654}, support = {/NH/NIH HHS/United States ; R01DE027980//NIDCR/NIH/ ; R56DE033249//NIDCR/NIH/ ; R01EY033622//NEI/NIH/ ; }, mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology/physiology ; Post-Acute COVID-19 Syndrome ; Microbiota ; Dysbiosis ; Mouth Mucosa/virology/immunology/microbiology ; Virus Internalization ; Mouth Diseases/virology/microbiology/immunology ; Angiotensin-Converting Enzyme 2/metabolism ; }, abstract = {SARS-CoV-2 is an oral pathogen that infects and replicates in mucosal and salivary epithelial cells, contributing to oral post-acute sequelae COVID-19 (PASC) and other oral and non-oral pathologies. While pre-existing inflammatory oral diseases provides a conducive environment for the virus, acute infection and persistence of SARS-CoV-2 can also results in oral microbiome dysbiosis that further worsens poor oral mucosal health. Indeed, oral PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, oral keratoses, and pulpitis suggesting significant bacterial contributions to SARS-CoV-2 and oral tissue tropism. Dysbiotic microbiome-induced inflammation can promote viral entry via angiotensin-converting enzyme receptor-2 (ACE2), serine transmembrane TMPRSS2 and possibly other non-canonical pathways. Additionally, metabolites derived from a dysbiotic microbiome can alter the physiological and biochemical pathways related to the metabolism of lipids, carbohydrates, and amino acids. This may promote a pro-inflammatory microenvironment, leading to immune exhaustion, loss of tolerance, and susceptibility to a variety of oral pathogens, causing acute and later chronic inflammation. Microbial release of mimics of host metallopeptidases related to furin, ADAM17 (A disintegrin and metalloproteinase 17), and glycoprotein metabolites can further aid viral attachment to T cell immunoglobulin-like (TIMs), enhancing viral entry while simultaneously depressing oral mucosal immune resistance and clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, also functionally assists with SARS-CoV-2 entry and extends the pathogenesis of PASC from the oral cavity to the brain, gut, or other non-oral tissues. Thus, poor oral health, characterised by disrupted oral microbiomes can promote viral tropism, weaken antiviral resistance, and heightens susceptibility to SARS-CoV-2 infection. This immune dysfunction also increases the risk of additional viral infections, exacerbating oral conditions like periodontal and endodontic diseases. These persistent oral health issues can contribute to systemic inflammation, creating bidirectional effects between oral and non-oral tissues, potentially leading to Post-Acute Sequelae of COVID-19 (PASC).}, } @article {pmid40074568, year = {2025}, author = {Giollo, A and Salvato, M and Doria, A}, title = {Recognizing the role of fibromyalgia in post-exertional malaise.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tem.2025.02.005}, pmid = {40074568}, issn = {1879-3061}, } @article {pmid40074502, year = {2025}, author = {Nugent, K}, title = {Postexertional Malaise and Rehabilitation in Long COVID.}, journal = {Chest}, volume = {167}, number = {3}, pages = {e95-e96}, doi = {10.1016/j.chest.2024.10.056}, pmid = {40074502}, issn = {1931-3543}, } @article {pmid40073919, year = {2025}, author = {Tan, YY and Loy, EXH and Tan, WZ and Tay, AT and Lim, JT and Chiew, CJ and Choolani, M and Lye, DC and Tan, KB and Wee, LE}, title = {Long COVID-19 in pregnancy: increased risk but modest incidence following mild Omicron infection in a boosted obstetric cohort during endemicity.}, journal = {American journal of obstetrics and gynecology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajog.2025.03.004}, pmid = {40073919}, issn = {1097-6868}, abstract = {BACKGROUND: Significant heterogeneity has been reported in estimates of long-term sequelae following SARS-CoV-2 infection in pregnant women, and most studies were conducted pre-Omicron and pre-dated vaccination rollout. Less severe COVID-19 attributed to milder Omicron may potentially attenuate risk of post-COVID-19 sequelae.

OBJECTIVE: We sought to examine long-term risk of new-incident multi-systemic sequelae following SARS-CoV-2 Delta/Omicron infection in a population-based cohort of pregnant women, contrasted against a)test-negatives; b)infected non-pregnant women of childbearing age. We hypothesize that increased risk of long-term sequelae post-SARS-CoV-2 infection in pregnancy persists into COVID-19 endemicity.

STUDY DESIGN: Retrospective population-based cohort study of all Singaporean pregnant women infected during Delta/Omicron-predominant transmission, and a) a contemporaneous test-negative pregnant group; b) infected non-pregnant women of child-bearing age, constructed using the national COVID-19 registry. Between-group-differences were adjusted for using inverse-propensity-weighting, and Cox-regression was utilized to estimate risks of new-incident post-acute diagnoses/symptoms reported in national healthcare-claims data, at 31-300 days post-infection RESULTS: 11,208 pregnant COVID-19 cases, 15,255 uninfected pregnant test-negatives, and 332,198 COVID-19 cases in non-pregnant women of child-bearing age were included. 72.1% (8079/11208) of pregnant COVID-19 cases were boosted, and 97.0% (10869/11208) were infected during Omicron-predominant transmission. Risk of any post-acute sequelae in pregnant COVID-19 cases was 1.6 times that of pregnant test-negatives (any post-acute diagnosis: adjusted-hazards-ratio, aHR=1.68[95%CI=1.24-2.26], p<0.001; any post-acute symptom: aHR=1.65[95%CI=1.23-2.22], p<0.001). The risk of long-COVID-19 was substantially increased with pregnancy; risk of any post-acute sequelae in pregnant COVID-19 cases was 13.4 times that observed amongst women of childbearing age infected outside of pregnancy (any post-acute diagnosis: aHR=13.39[95%CI=10.55-16.98], p<0.001; any post-acute symptom: aHR=21.82[95%CI=16.77-28.41], p<0.001). However, though risk was increased, absolute incidence was modest; <1% of pregnant COVID-19 cases reported any post-acute sequelae. In subgroup analyses, pregnant COVID-19 cases infected during the third trimester were at higher risk for post-acute sequelae. Risk of any post-acute sequelae in pregnant COVID-19 cases infected during the third trimester was 2-3 times that of pregnant test-negatives (any post-acute diagnosis: aHR=2.03[95%CI=1.32-3.15], p<0.001; any post-acute symptom: aHR=3.91[95%CI=2.25-6.80], p<0.001), whereas risk of post-acute sequelae was not significantly increased in pregnant COVID-19 cases infected before the third trimester, versus test-negatives. Risk of post-acute sequelae was not significantly different in pregnant COVID-19 cases boosted prior to infection, versus unboosted cases.

CONCLUSION: Increased risk of long-term multi-systemic sequelae 31-300 days post-COVID-19 was still observed in a highly-vaccinated population-based cohort of pregnant women predominantly infected with the mild Omicron SARS-CoV-2 variant, versus test-negatives and infected non-pregnant women of childbearing age. Women infected in the third trimester of pregnancy were at increased risk of post-acute sequelae. However, <1% reported post-acute sequelae following SARS-CoV-2 infection. The beneficial impact of vaccination might have attenuated overall risk of post-acute sequelae, given that 99% of pregnant women had completed primary vaccination; though prior receipt of an additional COVID-19 booster dose did not significantly attenuate risk of post-acute sequelae in pregnancy (versus unboosted individuals). Low prevalence of long-term sequelae following COVID-19 in a highly-vaccinated pregnant cohort highlights the importance of maternal COVID-19 vaccination; this is of significance given increasing vaccine hesitancy amongst pregnant women during COVID-19 endemicity.}, } @article {pmid40073162, year = {2025}, author = {Taher, MK and Salzman, T and Banal, A and Morissette, K and Domingo, FR and Cheung, AM and Cooper, CL and Boland, L and Zuckermann, AM and Mullah, MA and Laprise, C and Colonna, R and Hashi, A and Rahman, P and Collins, E and Corrin, T and Waddell, LA and Pagaduan, JE and Ahmad, R and Jaramillo Garcia, AP}, title = {Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence.}, journal = {Health promotion and chronic disease prevention in Canada : research, policy and practice}, volume = {45}, number = {3}, pages = {112-138}, doi = {10.24095/hpcdp.45.3.02}, pmid = {40073162}, issn = {2368-738X}, mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health/statistics & numerical data ; Survivors/statistics & numerical data ; }, abstract = {INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).

METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.

RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.

CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.}, } @article {pmid40072491, year = {2025}, author = {Cao, T and Reeder, HT and Foulkes, AS}, title = {Sparse Bernoulli mixture modeling with negative-unlabeled data: an approach to identify and characterize long COVID.}, journal = {Biometrics}, volume = {81}, number = {1}, pages = {}, doi = {10.1093/biomtc/ujaf021}, pmid = {40072491}, issn = {1541-0420}, support = {/NH/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; *Models, Statistical ; *Post-Acute COVID-19 Syndrome ; *Computer Simulation ; *Algorithms ; SARS-CoV-2 ; Bayes Theorem ; Adult ; Cohort Studies ; }, abstract = {SARS-CoV-2-infected individuals have reported a diverse collection of persistent and often debilitating symptoms commonly referred to as long COVID or post-acute sequelae of SARS-CoV-2 (PASC). Identifying PASC and its subphenotypes is challenging because available data are "negative-unlabeled" as uninfected individuals must be PASC negative, but those with prior infection have unknown PASC status. Moreover, feature selection among many potentially informative characteristics can facilitate reaching a concise and easily interpretable PASC definition. Therefore, to characterize PASC and the spectrum of PASC subphenotypes while identifying a minimal set of features, we propose a Bernoulli mixture model with novel parameterization to accommodate negative-unlabeled data and Bayesian priors to induce sparsity. We present an efficient expectation-maximization algorithm for estimation, and a grid search procedure to select the number of clusters and level of sparsity. We evaluate the proposed method with a simulation study and an analysis of data on self-reported symptoms from the ongoing Researching COVID to Enhance Recovery-Adult Cohort study.}, } @article {pmid40071827, year = {2025}, author = {Hurt, RT and Ganesh, R and Schroeder, DR and Hanson, JL and Fokken, SC and Overgaard, JD and Bauer, BA and Thilagar, BP and Aakre, CA and Pruthi, S and Croghan, IT}, title = {Using a Wearable Brain Activity Sensing Device in the Treatment of Long COVID Symptoms in an Open-Label Clinical Trial.}, journal = {Journal of primary care & community health}, volume = {16}, number = {}, pages = {21501319251325639}, doi = {10.1177/21501319251325639}, pmid = {40071827}, issn = {2150-1327}, mesh = {Humans ; Female ; Male ; *COVID-19 ; Middle Aged ; *Wearable Electronic Devices ; *Electroencephalography ; Pilot Projects ; *Quality of Life ; Adult ; Stress, Psychological/therapy ; Anxiety ; Patient Satisfaction ; Brain/physiopathology ; Feasibility Studies ; SARS-CoV-2 ; Self Efficacy ; Cognition ; }, abstract = {OBJECTIVE: This study evaluated the feasibility and satisfaction of using a wearable brain activity sensing device for stress reduction among patients experiencing Long COVID (LC).

PATIENTS AND METHODS: Patients with LC (N = 45) were invited to participate in an open-label pilot study. Participants were asked to use a brain-sensing electroencephalogram (S-EEG) wearable device (Muse-S™) daily for 90 days and followed for an additional 90 days (180 days total participation). Study enrollment began June 28, 2022, and ended July 28, 2023.

RESULTS: Patients were predominantly female (82%), white (96%), and with an average age of 47.6 (±12.5) years. At the end of treatment (90 days), cognition, sleep, self-efficacy, and quality-of-life quality of life improved (P < .001 to P = .04). In addition, stress and anxiety were significantly reduced (P < .001). These significant changes persisted by end-of-study (180 days). For stress (P = .023) and anxiety (P = .033), a change from the baseline during follow-up was significantly associated with the amount of S-EEG usage. The end-of-study satisfaction survey indicated that patients were very satisfied with the S-EEG device, and 97% planned to continue using it.

CONCLUSION: Results suggest that the S-EEG device improved cognition in LC, which is one of the main severe symptoms we see in our LC clinic. In addition, it helped reduce stress and anxiety. These findings have important clinical implications for LC patients using S-EEG as an adjunct to concurrent LC clinical care which includes pharmacotherapies.}, } @article {pmid40071640, year = {2025}, author = {Hedberg, P and van der Werff, SD and Nauclér, P}, title = {The effect of COVID-19 vaccination on the risk of persistent post COVID-19 condition: Cohort study.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf133}, pmid = {40071640}, issn = {1537-6613}, abstract = {We conducted a population-based cohort study in Stockholm, Sweden, to investigate the effect of COVID-19 vaccination on the risk of developing persistent PCC in individuals surviving the first year after a SARS-CoV-2 infection. 331,042 individuals were included, of which 852 had persistent PCC. The adjusted RR (95% CI) for developing persistent PCC compared with unvaccinated individuals was 0.81 (0.59-1.10) for 1 dose, 0.42 (0.35-0.52) for 2 doses, and 0.37 (0.27-0.52) for three doses. Reduced risks for vaccinated individuals were also observed when restricting the analyses to pre-Omicron and Omicron, as well as all subgroups including sex, age, and previous infection.}, } @article {pmid40071259, year = {2025}, author = {Velati, D and Puoti, M}, title = {Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies.}, journal = {Le infezioni in medicina}, volume = {33}, number = {1}, pages = {64-75}, doi = {10.53854/liim-3301-6}, pmid = {40071259}, issn = {2532-8689}, abstract = {The therapeutic armamentarium that has been made available from the beginning of the emergency phase of the COVID-19 pandemic to date is briefly reviewed, and an overview of the real-world clinical evidence published by the Italian medical and scientific community during the last three years is presented herein. Prior to the introduction of a vaccine for SARS-CoV-2, several treatment options were implemented from the onset given the evidence that a "cytokine storm" was present during infection with SARS-CoV-2. However, with the exception of tocilizumab, baricitinib and perhaps anakinra, most studies with anti-cytokine biological agents in patients with severe COVID-19 did not show any significant clinical improvement or decrease in mortality at day 28. The same is true of several repurposed drugs including ivermectin, lactoferrin, interferon ß-1a, lopinavir/ritonavir alone or combined with hydroxychloroquine, and darunavir/ cobicistat, which did not show any benefits in clinical status or mortality. Treatment with neutralizing monoclonal antibodies (mAbs) for COVID-19 is changing continually with the evolution of new viral variants. In Italy, current indications for treatment of COVID-19 outpatients underline that the use of specific mAbs may vary over time depending on the prevalent SARS-CoV-2 variant and the sensitivity to the different mAbs available. Three antiviral drugs against SARS-CoV-2 were studied extensively and initially available in Italy: remdesivir, molnupiravir, and nirmaltrelvir/ritonavir, but at present the latter is the only oral antiviral for SARS-CoV-2 available in Italy. Several real-world studies for the use of nirmatrelvir/ ritonavir in the Italian population have been published. Among the current unmet needs, a clear and universal definition for long COVID along with treatments and prevention are still lacking as is clarity of the pathogenetic mechanisms responsible for it.}, } @article {pmid40071133, year = {2025}, author = {Monsalve, DM and Acosta-Ampudia, Y and Acosta, NG and Celis-Andrade, M and Şahin, A and Yilmaz, AM and Shoenfeld, Y and Ramírez-Santana, C}, title = {NETosis: A key player in autoimmunity, COVID-19, and long COVID.}, journal = {Journal of translational autoimmunity}, volume = {10}, number = {}, pages = {100280}, doi = {10.1016/j.jtauto.2025.100280}, pmid = {40071133}, issn = {2589-9090}, abstract = {NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.}, } @article {pmid40070822, year = {2025}, author = {Diaz, M and Mikulski, Z and Leaman, D and Gandarilla, A and Da Silva, N and Verkoczy, A and Zhang, J and Verkoczy, L}, title = {SARS-CoV-2 spike peptide analysis reveals a highly conserved region that elicits potentially pathogenic autoantibodies: implications to pan-coronavirus vaccine development.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1488388}, doi = {10.3389/fimmu.2025.1488388}, pmid = {40070822}, issn = {1664-3224}, mesh = {*Spike Glycoprotein, Coronavirus/immunology ; *SARS-CoV-2/immunology ; *Autoantibodies/immunology ; Humans ; *COVID-19/immunology/prevention & control ; *Antibodies, Viral/immunology/blood ; *COVID-19 Vaccines/immunology ; Animals ; Vaccine Development ; Mice ; Epitopes/immunology ; Peptides/immunology ; Immunoglobulin G/immunology/blood ; Female ; Conserved Sequence ; }, abstract = {The SARS-CoV-2 pandemic, while subsiding, continues to plague the world as new variants emerge. Millions have died, and millions more battle with the debilitating symptoms of a clinical entity known as long Covid. The biggest challenge remains combating an ever-changing variant landscape that threatens immune evasion from vaccine and prior infection-generated immunity. In addition, the sequelae of symptoms associated with long Covid almost certainly point to multiple pathologies that range from direct damage to organs during infection to a potential role for infection-induced autoreactive antibodies in promoting autoimmune-like conditions in these patients. In this study, a peptide scan of the SARS-CoV-2 spike protein was done to detect novel, highly conserved linear epitopes that do not elicit autoantibodies. We identified eight predicted linear epitopes capable of eliciting anti-spike IgG antibodies. Immunizations alternating peptide conjugated to KLH with the full trimer yielded the highest antibody levels, but homologous immunization with some of the peptides also yielded high levels when an additional immunization step was added. Of all regions tested, the stem helix adjacent to the heptad repeat 2 (HR2) region also elicited high levels of autoreactive antibodies to known autoantigens in common systemic autoimmune disorders such as lupus and scleroderma and may contribute to the long Covid syndrome seen in some patients. Implications to vaccine design are discussed.}, } @article {pmid40070691, year = {2025}, author = {Adamiec-Mroczek, J and Kluz, J and Chwałek, S and Rabczyński, M and Gostomska-Pampuch, K and Lewandowski, Ł and Misiuk-Hojło, M and Ponikowska, B and Chourasia, G and Dumas, I and Gamian, A and Fiodorenko-Dumas, Ż and Konopska, B and Gola, A and Konikowska, K and Strub, D and Bronowicka-Szydełko, A and Madziarska, K}, title = {Development of an enzyme-linked immunosorbent assay (ELISA) for determining neutrophil elastase (NE) - a potential useful marker of multi-organ damage observed in COVID-19 and post-Covid-19 (PCS).}, journal = {Frontiers in molecular biosciences}, volume = {12}, number = {}, pages = {1542898}, doi = {10.3389/fmolb.2025.1542898}, pmid = {40070691}, issn = {2296-889X}, abstract = {BACKGROUND: The ongoing post-COVID-19 syndrome (PCS) epidemic, causing complications of diverse etiology, necessitates the search for new diagnostic markers and the development of widely accessible methods for their detection. This would enable the prognosis of PCS progression and faster implementation of targeted treatments. One potential marker is neutrophil elastase (NE), whose elevated levels in the blood during PCS may result from organ damage caused by increased secretion of severe inflammatory mediators or amyloidosis resulting from the interaction of NE with SARS-CoV-2. The aim of this publication is to present a step-by-step method for designing an enzymatic ELISA test, enabling the quantitative assessment of NE in the blood serum of patients.

METHODS: NE was measured using the designed ELISA test.

RESULTS: The study outlines all the steps necessary for designing and optimizing the ELISA test, including the selection of standards, primary and secondary antibodies, and their dilutions. Using the test, elevated NE levels were demonstrated in patients with advanced-stage diabetic nephropathy after symptomatic COVID-19, compared to a relative group of patients sampled before COVID-19.

CONCLUSION: The undertaken efforts enabled the development of a test with high performance parameters (initially set sensitivity: ≥40 pg/μL; intra-assay precision: 7%; inter-assay precision <20%). No significant cross-reactivity with other tested proteins was observed. Serial dilution of plasma samples resulted in a proportional decrease in signal intensity.}, } @article {pmid40068974, year = {2025}, author = {Emery, I and Rosen, C}, title = {Adult Long Coronavirus Disease 2019: Definition, Prevalence Pathophysiology, and Clinical Manifestations.}, journal = {Infectious disease clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.idc.2025.02.007}, pmid = {40068974}, issn = {1557-9824}, abstract = {Long coronavirus disease 2019 (COVID-19) is a multisystem disorder with variable manifestations and duration. One in 10 people with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will develop some manifestation of long COVID-19. Currently, there is no one single etiologic factor for the symptoms and signs of long COVID-19 beyond exposure to the SARS-CoV-2 virus. There are multiple theories about the pathophysiology ranging from viral persistence, reactivation, autoimmunity, and immune depletion. Certain risk factors have been identified including female sex, severe acute/hospitalized COVID-19, previous infections with SARS-CoV-2, and absence of vaccinations.}, } @article {pmid40065411, year = {2025}, author = {Ryu, S and Allgood, KL and Xie, Y and Orellana, RC and Fleischer, NL}, title = {Minority health social vulnerability index and long COVID illness among a statewide, population-based study of adults with polymerase chain reaction-confirmed SARS-CoV-2.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {83}, number = {1}, pages = {64}, pmid = {40065411}, issn = {0778-7367}, support = {6 NU50CK000510-02-04 and 1 NH75OT000078-01-00/CC/CDC HHS/United States ; }, abstract = {BACKGROUND: The COVID-19 pandemic has disproportionately affected socially vulnerable communities. Some individuals experience persistent symptoms and conditions of COVID-19 illness known as long COVID. As little research has examined how social vulnerability is related to long COVID, we studied this topic using Minority Health Social Vulnerability Index (MHSVI), specifically created for the COVID-19 pandemic in the U.S.

METHODS: We merged county-level MHSVI data with population-based data of Michigan adults with PCR-confirmed SARS-CoV-2 infection between March 2020 and May 2022 based on respondents' county of residence. We examined the relationship between county-level MHSVI (binary: high social vulnerability ≥ 75th percentile) and two long COVID measurements, assessed a median of 18.8 months after their initial infection: (1) ongoing long COVID (yes/no) and (2) long COVID diagnosis (yes/no). We conducted modified Poisson regression models with robust standard errors to estimate prevalence ratio (PR) between associations of MHSVI and long COVID overall and by six MHSVI themes (socioeconomic status, household composition/disability, minority/language, housing type/transportation, healthcare access, medical vulnerability), adjusting for individual-level and county-level covariates.

RESULTS: Living in high MHSVI counties was not associated with ongoing long COVID or long COVID diagnosis. However, the associations differed by theme of MHSVI: respondents in highly socially vulnerable counties assessed by medical vulnerability had 1.32 times higher prevalence of long COVID diagnosis (95% CI:1.12 - 1.57). There were no statistically significant associations in other themes after the adjustment for covariates.

CONCLUSIONS: Our findings suggest the importance of upstream social determinants of health during public health emergencies and provide evidence that medically vulnerable communities need additional public health resources to cope with long COVID among their residents.}, } @article {pmid40065313, year = {2025}, author = {Adam, LC and Boesl, F and Raeder, V and Breuer, A and Bremer, B and Audebert, HJ and Franke, C}, title = {The legacy of the COVID-19 pandemic for the healthcare environment: the establishment of long COVID/ Post-COVID-19 condition follow-up outpatient clinics in Germany.}, journal = {BMC health services research}, volume = {25}, number = {1}, pages = {360}, pmid = {40065313}, issn = {1472-6963}, mesh = {Humans ; Germany/epidemiology ; *COVID-19/epidemiology/therapy ; Cross-Sectional Studies ; Female ; *Ambulatory Care Facilities ; Male ; *SARS-CoV-2 ; Middle Aged ; Pandemics ; Adult ; Post-Acute COVID-19 Syndrome ; Aftercare ; Aged ; }, abstract = {BACKGROUND: Since 2020, several specialized follow-up outpatient clinics have been established across Germany to address the complex needs of patients with Long COVID/ Post-COVID-19 Condition (PCC). This article reviews the current landscape of these specialized clinics in Germany and critically evaluates their diagnostic and treatment algorithms.

METHODS: This study employed a mixed-method approach, combining publicly available information on post-COVID-19 outpatient clinics with an observational cross-sectional online survey among lead doctors of PCC follow-up outpatient clinics in Germany. The survey was conducted from November 2023 to January 2024. Descriptive statistics and t-tests for group-comparisons were employed, with statistical significance set at p < 0.05.

RESULTS: At the time of the survey, 112 specialized PCC outpatient clinics were identified in Germany through publicly available information. Forty-five PCC outpatient clinic lead doctors (40.2%) responded to our survey. Treatment of PCC patients is personalized and symptom-oriented rather than standardized. Patient characteristics of the two identified main treatment domains, focusing on respiratory and neurocognitive symptoms, differed only in sex distribution. A higher proportion of females (63.9%) presented with pulmonary symptoms compared to patients with neurocognitive impairments (50.2%, p < 0.05). The level of distress among patients is generally perceived as high and outpatient clinic lead doctors are convinced that their outpatient counseling services offer significant benefits.

CONCLUSIONS: As the demand for PCC follow-up outpatient clinics persists, the establishment of new services continues, particularly to address the growing need for neurocognitive care services. PCC outpatient care is currently personalized and symptom-orientated, leading to high variability across clinics. Further standardization of treatment protocols and diagnostic algorithms could improve patient care and facilitate professional exchange.}, } @article {pmid40064948, year = {2025}, author = {Ranque, B and Garner, P and Allenbach, Y and Hupin, D and David, AS and Wade, D and Sharpe, M and Garcin, B and Little, P and Tinazzi, M and Fink, P and Hamilton, W and Peto, T and Lemogne, C and Wyller, VBB and Chalder, T and Coebergh, J}, title = {Publisher Correction: Muscle abnormalities in Long COVID.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2358}, doi = {10.1038/s41467-025-57761-2}, pmid = {40064948}, issn = {2041-1723}, } @article {pmid40063691, year = {2025}, author = {Molmans, THJ}, title = {Why the threat of psychosocial reductionism to patients in psychiatry and medicine is rather ignored.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf091}, pmid = {40063691}, issn = {1460-2156}, } @article {pmid40063321, year = {2025}, author = {Chu, L and Bishof, K and Dumes, AA and Wesley Ely, E and Joseph, PV and Troxel, AB and , }, title = {The 2024 National Academies of Sciences, Engineering, and Medicine Long COVID Definition: What Clinicians Need to Know.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {40063321}, issn = {1525-1497}, abstract = {Millions of Americans affected by Long COVID (LC) report difficulty accessing care and support. One barrier is obtaining a diagnosis. In response, US federal agencies commissioned a National Academies of Sciences, Engineering, and Medicine (NASEM) committee to re-examine the existing federal definitions for LC. The Committee concluded that LC is "an infection-associated chronic condition (IACC) occurring after SARS-CoV-2 infection that is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that can present as singular or multiple symptoms and/or diagnosable conditions." The full report was released in June 2024. We briefly highlight features and aspects of the definition that may help clinicians identify those who remain undiagnosed and improve care for all LC patients.}, } @article {pmid40062993, year = {2025}, author = {Cavarelli, M}, title = {Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID.}, journal = {Virologie (Montrouge, France)}, volume = {29}, number = {1}, pages = {57-68}, doi = {10.1684/vir.2025.1074}, pmid = {40062993}, issn = {1267-8694}, mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/physiology/immunology ; *Post-Acute COVID-19 Syndrome ; Inflammation/virology ; Gastrointestinal Tract/virology ; }, abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.}, } @article {pmid40062991, year = {2025}, author = {Cavarelli, M}, title = {[Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID].}, journal = {Virologie (Montrouge, France)}, volume = {29}, number = {1}, pages = {41-53}, doi = {10.1684/vir.2025.1073}, pmid = {40062991}, issn = {1267-8694}, mesh = {Humans ; *COVID-19/immunology/virology ; *SARS-CoV-2/physiology ; *Post-Acute COVID-19 Syndrome ; Inflammation/virology ; }, abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.}, } @article {pmid40062652, year = {2025}, author = {Zhang, X and Hery, C and McLaughlin, EM and Woods, NF and Neuhouser, ML and Harris, H and Gower, EW and Wactawski-Wende, J and Shadyab, AH and Wallace, RB and Paskett, ED}, title = {The Association of Long COVID-19 Symptoms, Physical Function, and Activities of Daily Living Among Older Women.}, journal = {Journal of the American Geriatrics Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgs.19434}, pmid = {40062652}, issn = {1532-5415}, support = {/HL/NHLBI NIH HHS/United States ; /NH/NIH HHS/United States ; //U.S. Department of Health and Human Services/ ; K00CA253745/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: The impact of COVID-19 on physical function (PF) outcomes among older adults remains unclear. We examined the long-term association between COVID, PF, and Activities of Daily Living (ADLs) among women from the Women's Health Initiative (WHI).

METHODS: Participants from the WHI who completed the COVID-19 survey (2021-2022) and annual survey (2022) were included. Self-reported data on COVID-19 testing and symptoms (2021-2022) were used. PF score and ADLs were evaluated pre- and post-COVID-19 survey by the 36-Item Short Form Survey PF subscale, the Lawton Instrumental Activities of Daily Living, and the Katz Index of Independence in ADL. Multivariable linear regression and logistic regression were used and adjusted for pre-COVID functioning to examine the association between COVID status, PF, and ADLs. The interaction between pre-COVID functioning and COVID status was tested.

RESULTS: Among the 13,933 WHI participants, 71.4% were aged ≥ 80 years, and 88.6% were Non-Hispanic White. Only 8.7% tested positive for COVID-19 (n = 1210), with 35.1% having long COVID (n = 425). The most common long COVID symptoms were fatigue (18.2%), malaise (12.2%), memory problems (12.1%), and brain fog (11.2%). Women who tested COVID+ had lower PF scores (60 vs. 65, p = 0.045) and were less likely to be able to do all ADLs without help (74% vs. 79.2%, p = 0.015) compared to those who never tested COVID+. After controlling for covariates, post-COVID PF scores did not differ by COVID status (p = 0.30), although pre-COVID PF scores were significantly linked to post-COVID scores (p < 0.001). Similarly, the odds of being able to do all ADLs without any help did not differ by COVID status (p = 0.31), with pre-COVID ADLs significantly associated with post-COVID ADLs (p < 0.001).

CONCLUSIONS: In older women, after accounting for pre-COVID functional status, the association between long COVID and lower functioning became nonsignificant. Our findings highlight the importance of preserving physical functioning among older women.}, } @article {pmid40061762, year = {2024}, author = {Bhambal, AM and Raj, A and Kumarasamy, B and Choudhary, P and Katiyar, R and Manikandan, S}, title = {POST-COVID SYNDROME - A Psychosomatic Burden for the Rima Oris. An Original Research.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {16}, number = {Suppl 5}, pages = {S4775-S4780}, pmid = {40061762}, issn = {0976-4879}, abstract = {BACKGROUND: Long COVID syndrome (LCS) is increasingly being recognized as a new clinical entity after SARS-CoV-2 infection. Symptoms persisting for more than three weeks after the diagnosis of COVID-19 characterize LCS. Incidence of it ranges from 10% to 35%. We conducted this study via digital platform, to evaluate the psychosomatic disorders of the oral cavity associated with LCS.

AIM AND OBJECTIVES: To assess the association of long COVID syndrome with oral psychosomatic disorders and to identify patients with long-COVID symptoms, Prevalence of psychosocial impact on the population and to do Comparative analysis among male and female.

MATERIALS AND METHODS: In this study a Pan-India survey was conducted in which a questionnaire was prepared on Google platform and shared online to participants who had suffered from SARS-CoV-2. Data was collected on a four phase record and statistical analysis was done. Comparisons of proportions between male and female were carried out with Chi square (χ²) test.

RESULTS: Results showed females being more affected mentally and psychologically. Males were affected by oro-pharyngeal problems. Majority of participants in the survey were not absolutely healthy after acquiring SARS-CoV-2 infection.

CONCLUSION: LCS is a multisystem disorder. There's a lack of knowledge in literature in the association of oral lesions with psychosomatic disorders in such individuals. The oral specialist can help diagnose such patients and help plan their lifestyle modification. Further research is required to formulate a standard classification for Long COVID Syndrome which will be help plan a multidisciplinary therapeutic approach.}, } @article {pmid40059070, year = {2025}, author = {Curtis, N}, title = {Long COVID in a highly vaccinated but largely unexposed Australian population following the 2022 SARS-CoV-2 Omicron wave.}, journal = {The Medical journal of Australia}, volume = {}, number = {}, pages = {}, doi = {10.5694/mja2.52619}, pmid = {40059070}, issn = {1326-5377}, } @article {pmid40059060, year = {2025}, author = {Woldegiorgis, M and Korda, RJ and Effler, PV}, title = {Long COVID in a highly vaccinated but largely unexposed Australian population following the 2022 SARS-CoV-2 Omicron wave.}, journal = {The Medical journal of Australia}, volume = {}, number = {}, pages = {}, doi = {10.5694/mja2.52620}, pmid = {40059060}, issn = {1326-5377}, } @article {pmid40056320, year = {2025}, author = {Zhao, Y and Zeng, G}, title = {The association between glucocorticoids and long COVID.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40056320}, issn = {1568-5608}, } @article {pmid40056074, year = {2025}, author = {Minor, GN and Kessler, OR and Fry, L and Huizenga, B and Johnson, S and Naini, SM and Shen, C and Wiitala, SJ and Basso, MR and Eskridge, CL and Holker, E and Logemann, AM and Waldron, EJ and Whiteside, DM}, title = {The relationship between performance validity Test failure, fatigue, and psychological functioning in Long COVID.}, journal = {The Clinical neuropsychologist}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/13854046.2025.2476798}, pmid = {40056074}, issn = {1744-4144}, abstract = {Objective: At times, patients with Long COVID fail performance validity tests (PVTs) for cognitive measures and symptom validity tests (SVTs) embedded in formal personality measures. This is the first study, to our knowledge, to examine whether self-reported symptoms on the Personality Assessment Inventory (PAI) and the Modified Fatigue Impact Scale (MFIS) were related to performance validity in Long COVID patients. Method: Participants were 175 individuals diagnosed with Long COVID who completed four PVTs, the MFIS, and the PAI. There was evidence for nots based on medical records review for 25.71% of the patients. Based on PVT performances, patients were assigned to one of three groups: Pass group (no PVT failures), Intermediate group (1 PVT failure), or Fail group (2+ PVT failures). Results: 84.57% of participants were in the Pass group, 9.14% in the Intermediate group, and 6.29% in the Fail group. There was a not a significant difference in external incentive frequency between groups. Only one significant group difference on the PAI scales and subscales was found, with slightly greater somatization symptoms (SOM-S) reported in the Fail group relative to the Pass group (η[2] = .03). The MFIS was not significantly different between groups. Conclusions: These findings suggest that PVT failure is not associated with fatigue or PAI responses, except on the somatization subscale.}, } @article {pmid40055683, year = {2025}, author = {Chai, Y and Lam, ICH and Man, KKC and Hayes, JF and Wan, EYF and Li, X and Chui, CSL and Lau, WCY and Lin, X and Yin, C and Fan, M and Chan, EW and Wong, ICK and Luo, H}, title = {Psychiatric and neuropsychiatric sequelae of COVID-19 within 2 years: a multinational cohort study.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {144}, pmid = {40055683}, issn = {1741-7015}, support = {C7154-20GF//University Grants Committee/ ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology/complications ; Male ; Female ; *Mental Disorders/epidemiology ; Middle Aged ; Adult ; Cohort Studies ; Aged ; Germany/epidemiology ; France/epidemiology ; SARS-CoV-2 ; Italy/epidemiology ; Young Adult ; United Kingdom/epidemiology ; United States/epidemiology ; }, abstract = {BACKGROUND: The long-term psychiatric and neuropsychiatric sequelae of COVID-19 across diverse populations remain not fully understood. This cohort study aims to investigate the short-, medium-, and long-term risks of psychiatric and neuropsychiatric disorders following COVID-19 infection in five countries.

METHODS: This population-based multinational network study used electronic medical records from France, Italy, Germany, and the UK and claims data from the USA. The initial target and comparator cohorts were identified using an exact matching approach based on age and sex. Individuals diagnosed with COVID-19 or those with a positive SARS-CoV-2 screening test between December 1, 2019, and December 1, 2020, were included as targets. Up to ten comparators without COVID-19 for each target were selected using the propensity score matching approach. All individuals were followed from the index date until the end of continuous enrolment or the last healthcare encounter. Cox proportional hazard regression models were fitted to estimate the risk of incident diagnosis of depression, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, psychoses, personality disorders, self-harm and suicide, sleep disorders, dementia, and neurodevelopmental disorders within the first 6 months (short-term), 6 months to 1 year (medium-term), and 1 to 2 years (long-term) post-infection.

RESULTS: A total of 303,251 individuals with COVID-19 and 22,108,925 individuals without COVID-19 from five countries were originally included. Within the first 6 months, individuals with COVID-19 had a significantly higher risk of any studied disorders in all databases, with Hazard Ratios (HRs) ranging from 1.14 (95% CI, 1.07-1.22) in Germany to 1.89 (1.64-2.17) in Italy. Increased risks were consistently observed for depression, anxiety disorders, and sleep disorders across almost all countries. During the medium- and long-term periods, higher risks were observed only for depression (medium-term: 1.29, 1.18-1.41; long-term: 1.36, 1.25-1.47), anxiety disorders (medium-term: 1.29, 1.20-1.38; long-term: 1.37, 1.29-1.47), and sleep disorders (medium-term: 1.10, 1.01-1.21; long-term: 1.14, 1.05-1.24) in France, and dementia (medium-term: 1.65, 1.28-2.10) in the UK.

CONCLUSIONS: Our study suggests that increased risks of psychiatric and neuropsychiatric outcomes were consistently observed only within, and not after, the 6-month observation period across all databases, except for certain conditions in specific countries.}, } @article {pmid40055348, year = {2025}, author = {Carmo, DS and Pezzulo, AA and Villacreses, RA and Eisenbeisz, ML and Anderson, RL and Dorin, SEV and Rittner, L and Lotufo, RA and Gerard, SE and Reinhardt, JM and Comellas, AP}, title = {Manual segmentation of opacities and consolidations on CT of long COVID patients from multiple annotators.}, journal = {Scientific data}, volume = {12}, number = {1}, pages = {402}, pmid = {40055348}, issn = {2052-4463}, support = {2019/21964-4//Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation)/ ; 2022/02344-8//Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation)/ ; 317133/2023-3//Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development)/ ; 313047/2022-7//Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development)/ ; 506728/2020-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education)/ ; }, mesh = {Humans ; *COVID-19/diagnostic imaging ; *Tomography, X-Ray Computed ; *Lung/diagnostic imaging ; *SARS-CoV-2 ; Pandemics ; }, abstract = {The field of supervised automated medical imaging segmentation suffers from relatively small datasets with ground truth labels. This is especially true for challenging segmentation problems that target structures with low contrast and ambiguous boundaries, such as ground glass opacities and consolidation in chest computed tomography images. In this work, we make available the first public dataset of ground glass opacity and consolidation in the lungs of Long COVID patients. The Long COVID Iowa-UNICAMP dataset (LongCIU) was built by three independent expert annotators, blindly segmenting the same 90 selected axial slices manually, without using any automated initialization. The public dataset includes the final consensus segmentation in addition to the individual segmentation from each annotator (360 slices total). This dataset is a valuable resource for training and validating new automated segmentation methods and for studying interrater uncertainty in the segmentation of lung opacities in computed tomography.}, } @article {pmid40054841, year = {2025}, author = {Zamorano-Vargas, JA and Izquierdo, M and Ramírez-Vélez, R}, title = {Oxygen uptake kinetics during postexercise recovery are impaired in long COVID-19 patients: a cross-sectional study.}, journal = {Revista espanola de cardiologia (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rec.2025.02.009}, pmid = {40054841}, issn = {1885-5857}, } @article {pmid40054707, year = {2025}, author = {Fleischer, NL and Slocum, E and Patel, A and Xie, Y and McKane, P and Lyon-Callo, S and Hirschtick, JL}, title = {Long COVID and new onset disability nearly two years after initial infection.}, journal = {American journal of preventive medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amepre.2025.02.013}, pmid = {40054707}, issn = {1873-2607}, abstract = {INTRODUCTION: The objective of this study was to determine the prevalence of ongoing Long COVID symptoms and related disability in a population-based cohort nearly two years after SARS-CoV-2 infection.

METHODS: Six domains of age-standardized disability (i.e., mobility, cognition, independent living, vision, hearing, self-care) were assessed by ongoing Long COVID status using cohort data from a population-based survey of adults with COVID-19 onset from March-December 2020 in Michigan. Baseline data were collected June 2020-October 2021 and follow-up data were collected January-November 2022. Associations between ongoing Long COVID and each domain of disability were also examined using adjusted modified Poisson regression models. Analyses were conducted 2024-2025.

RESULTS: Nearly two years after initial infection, 24.0% of 1,547 respondents reported ongoing Long COVID symptoms. When comparing disability status four weeks prior to COVID-19 illness to the time of the follow-up survey, respondents with ongoing Long COVID symptoms had large increases in the prevalence of cognition (8.8% to 45.3%), mobility (12.7% to 40.0%), independent living (4.7% to 20.7%), and self-care (2.1% to 10.9%) disability, and more modest increases in the prevalence of vision and hearing disability. Respondents without ongoing Long COVID symptoms experienced smaller increases in disability prevalence. In regression models, ongoing Long COVID was associated with higher prevalence of all six disability domains.

CONCLUSIONS: The ongoing burden of Long COVID and related disability is substantial and warrants increased attention by the public health and medical communities.}, } @article {pmid40053784, year = {2025}, author = {Li, Y and Zhou, J and Wei, Z and Liang, L and Xu, H and Lv, C and Liu, G and Li, W and Wu, X and Xiao, Y and Sunzi, K}, title = {Efficacy and Safety of Acupuncture for Post-COVID-19 Insomnia: Protocol for a Systematic Review and Meta-Analysis.}, journal = {JMIR research protocols}, volume = {14}, number = {}, pages = {e69417}, doi = {10.2196/69417}, pmid = {40053784}, issn = {1929-0748}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy ; *Systematic Reviews as Topic ; *COVID-19/complications/therapy ; *Meta-Analysis as Topic ; *Acupuncture Therapy/methods/adverse effects ; Treatment Outcome ; Pandemics ; SARS-CoV-2 ; Coronavirus Infections/therapy/complications ; Pneumonia, Viral/therapy/complications ; Research Design ; }, abstract = {BACKGROUND: The COVID-19 pandemic has had a profound global impact, leading to a range of persistent sequelae referred to as post-COVID-19 condition or "long COVID" that continue to affect patients worldwide. Among these sequelae, post-COVID-19 insomnia (PCI) has emerged as a significant issue. Conventional treatments, including cognitive behavioral therapy and pharmacological interventions, face limitations such as variable efficacy, potential side effects, and substantial costs. Recently, acupuncture has gained traction due to its efficacy, cost-effectiveness, and safety profile.

OBJECTIVE: This study aims to conduct a meta-analysis and systematic review evaluating the efficacy and safety of acupuncture for the treatment of PCI to delineate the optimal modality, intervention frequency, and duration for achieving the most beneficial outcomes, thereby providing a comprehensive understanding of acupuncture's role in managing PCI, contributing to evidence-based clinical practice, and informing clinical decision-making.

METHODS: Electronic searches will be performed in 12 databases from inception to October 2024 without language restrictions. This includes both English databases (PubMed, Cochrane Library, Web of Science, Embase, OVID and Scopus), as well as Chinese databases (China National Knowledge Infrastructure, Wan-Fang Data, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Duxiu Database and the Chinese Clinical Trial Registry Center). Randomized controlled trials on acupuncture for PCI will be included. Primary outcomes will include the response rate and insomnia severity; secondary outcomes will include the Traditional Chinese Medicine Symptom Scale (TCMSS) and adverse event rates. Data synthesis will use risk ratios for dichotomous data and mean differences for continuous data. Study selection, data extraction, and quality assessment will be conducted independently by 2 reviewers. Methodological quality of eligible studies will be evaluated following the Cochrane Handbook for Systematic Reviews of Interventions (version 6.3). Meta-analysis will be performed with RevMan 5.3.

RESULTS: Based on the data on response rate, insomnia severity, TCMSS score, and adverse event rates, this study will provide an evidence-based review of the efficacy and safety of acupuncture for PCI treatment.

CONCLUSIONS: This systematic review will present the current evidence for acupuncture for PCI, aiming to inform clinical practices and decision-making and to enhance the understanding of acupuncture's role in managing PCI. Furthermore, it will identify research gaps and suggest potential areas for future investigation.

TRIAL REGISTRATION: PROSPERO CRD42024499284; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=499284.

DERR1-10.2196/69417.}, } @article {pmid40053748, year = {2025}, author = {Mandel, HL and Shah, SN and Bailey, LC and Carton, T and Chen, Y and Esquenazi-Karonika, S and Haendel, M and Hornig, M and Kaushal, R and Oliveira, CR and Perlowski, AA and Pfaff, E and Rao, S and Razzaghi, H and Seibert, E and Thomas, GL and Weiner, MG and Thorpe, LE and Divers, J and , }, title = {Opportunities and Challenges in Using Electronic Health Record Systems to Study Postacute Sequelae of SARS-CoV-2 Infection: Insights From the NIH RECOVER Initiative.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e59217}, doi = {10.2196/59217}, pmid = {40053748}, issn = {1438-8871}, mesh = {Humans ; *COVID-19/epidemiology ; *Electronic Health Records ; *National Institutes of Health (U.S.) ; United States ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The benefits and challenges of electronic health records (EHRs) as data sources for clinical and epidemiologic research have been well described. However, several factors are important to consider when using EHR data to study novel, emerging, and multifaceted conditions such as postacute sequelae of SARS-CoV-2 infection or long COVID. In this article, we present opportunities and challenges of using EHR data to improve our understanding of long COVID, based on lessons learned from the National Institutes of Health (NIH)-funded RECOVER (REsearching COVID to Enhance Recovery) Initiative, and suggest steps to maximize the usefulness of EHR data when performing long COVID research.}, } @article {pmid40053075, year = {2025}, author = {Juett, LA and Funnell, MP and Carroll, HA and James, LJ and Mears, SA}, title = {24 h severe fluid restriction increases a biomarker of renal injury in healthy males.}, journal = {European journal of applied physiology}, volume = {}, number = {}, pages = {}, pmid = {40053075}, issn = {1439-6327}, abstract = {PURPOSE: Exercise-induced hypohydration exacerbates biomarkers of renal injury, but studies isolating the effects of hypohydration without exercise have produced mixed findings. This study investigated the effects of 24-h severe fluid restriction on biomarkers of renal injury and glucose tolerance.

METHODS: Fifteen males (age: 27 ± 5 y; BMI: 24.1 ± 3.8 kg/m[2]) completed two randomised trials, involving consuming either 40 mL/kg body mass water to maintain euhydration (EU) or severe fluid restriction via limiting water consumption to 100 mL (HYP). A standardised dry food diet was consumed in both trials (~ 300 g water). At baseline and 24 h post-baseline, nude body mass, and blood and urine samples (additional urine sample at 12 h) were collected. An oral glucose tolerance test was conducted after 24-h post-baseline measurements (n = 12).

RESULTS: At 24 h, body mass loss (HYP: - 1.52 ± 0.34%, EU: - 0.24 ± 0.40%), plasma volume loss, serum, and urine osmolality were greater in HYP than EU (P ≤ 0.004). Osmolality-corrected urinary kidney injury molecule-1 (uKIM-1) concentrations were greater in HYP at 12 (HYP: 1.097 ± 0.587 ng/mOsm, EU: 0.570 ± 0.408 ng/mOsm; P < 0.001) and 24-h (HYP: 1.932 ± 1.173 ng/mOsm, EU: 1.599 ± 1.012 ng/mOsm; P = 0.01). There was no trial-by-time interactions for osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (P = 0.781) or plasma glucose (P = 0.550) and insulin (P = 0.193) concentrations.

CONCLUSION: Hypohydration produced by 24-h fluid restriction increased proximal tubular injury but did not affect glucose tolerance.}, } @article {pmid40051665, year = {2025}, author = {Sakellaropoulos, SG and Sakellaropoulos, PG and Steinberg, BS and Rogers, C and Ismael, O and Scholl, EW and Mohammed, M and Mitsis, A and Patrinou, NG}, title = {Five Years of Long COVID Syndrome: An Updated Review on Cardiometabolic and Psychiatric Aspects.}, journal = {Cardiology research}, volume = {16}, number = {2}, pages = {81-85}, pmid = {40051665}, issn = {1923-2829}, abstract = {Five years after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there is still a significant number of people who have survived COVID-19 but never fully recovered from the disease. They go through an odyssey of doctor visits and a multitude of diagnostic tests, which ultimately do not provide concrete correlations and answers to the question of how exactly long COVID (LC) affects both physical and mental health, and performance. Often, not even highly technical and highly specialized methods, such as cardiac magnetic resonance imaging (MRI), can provide further explanation. Various research efforts continue to investigate the causes, effects and possible treatments of LC, particularly its impact on cognition and mental health. Patients with LC may experience persistent symptoms, but new symptoms also occur. Based on available studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only affect the pulmonary system, but nearly every major system and organ, from the brain and heart to the kidneys and immune system. What mechanisms could explain the persistent symptoms of LC and the inadequate recovery? How valuable is an early internal and neurological examination, particularly in the context of psychotherapy? In this review, we examined which factors could contribute to the persistence of LC symptoms and to what extent mitochondrial impairment by LC can explain the symptoms of LC.}, } @article {pmid40051430, year = {2025}, author = {Pathak, A and Agrawal, DK}, title = {Role of Gut Microbiota in Long COVID: Impact on Immune Function and Organ System Health.}, journal = {Archives of microbiology & immunology}, volume = {9}, number = {1}, pages = {38-53}, pmid = {40051430}, issn = {2572-9365}, abstract = {SARS-CoV-2 infection has led to a range of long-lasting symptoms, collectively referred to as long COVID. Current research highlights the critical role of angiotensin-converting enzyme 2 (ACE2) in regulating gut microbiota diversity, vascular function, and homeostasis within the renin-angiotensin system (RAS). ACE2 is utilized by the SARS-CoV-2 virus to enter host cells, but its downregulation following infection contributes to gut microbiota dysbiosis and RAS disruption. These imbalances have been linked to a range of long COVID symptoms, including joint pain, chest pain, chronic cough, fatigue, brain fog, anxiety, depression, myalgia, peripheral neuropathy, memory difficulties, and impaired attention. This review investigates the dysregulation caused by SARS-CoV-2 infection and the long-term effects it has on various organ systems, including the musculoskeletal, neurological, renal, respiratory, and cardiovascular systems. We explored the bidirectional interactions between the gut microbiota, immune function, and these organ systems, focusing on how microbiota dysregulation contributes to the chronic inflammation and dysfunction observed in long COVID symptoms. Understanding these interactions is key for identifying effective therapeutic strategies and interventional targets aimed at mitigating the impact of long COVID on organ health and improving patient outcomes.}, } @article {pmid40049177, year = {2025}, author = {Relyea, M and Buddhadev, HH and Chalmers, GR and Bennett, S}, title = {Comparison of Balance Confidence in Older Adults With and Without Long-Haul COVID-19.}, journal = {Journal of aging and physical activity}, volume = {}, number = {}, pages = {1-8}, doi = {10.1123/japa.2024-0116}, pmid = {40049177}, issn = {1543-267X}, abstract = {BACKGROUND/OBJECTIVES: The effects of long COVID-19 on balance and fall risk in older adults are unknown. This study aimed to explore the relationship between balance confidence/fall risk, as assessed by the Activities-Specific Balance Confidence Scale and the Falls Efficacy Scale-International, and long COVID-19 status in older adults.

METHODS: This study assessed balance confidence and concern of falling in older adults (≥60 years) with long COVID-19 (long-haulers, n = 30) compared with older adults who experienced COVID-19 but not long COVID-19 (non-long-haulers, n = 60) and older adults (controls) who self-reported never having COVID-19 (n = 52). Participants gave informed consent and completed the Activities-Specific Balance Confidence Scale and the Falls Efficacy Scale-International. Data were analyzed using Kruskal-Wallis tests.

RESULTS: Long-haulers had lower balance confidence and greater concern of falling compared with non-long-haulers (p < .001; p < .001) and controls (p = .011; p = .027).

CONCLUSION: Older adults with long-haul COVID-19 have decreased balance confidence and increased concern of falling compared with non-long-haulers and healthy controls, which may indicate a greater fall risk. Significance/Implications: Older adults with long COVID-19 may have a heightened need for resources and healthcare services related to fall prevention. Consideration of long COVID-19 status may be an important factor in improving older adult's outcomes.}, } @article {pmid40048846, year = {2025}, author = {Namie, H and Takazono, T and Kawasaki, R and Yano, H and Ito, Y and Nakada, N and Hirayama, T and Yoshida, M and Takeda, K and Ide, S and Takemoto, S and Iwanaga, N and Tashiro, M and Hosogaya, N and Ishimoto, H and Sakamoto, N and Obase, Y and Sawai, T and Hashiguchi, K and Fukuda, Y and Kobayashi, T and Matsumoto, N and Norimura, D and Kawano, T and Hanaka, T and Watanabe, T and Komiya, K and Miyazaki, T and Ishii, H and Yatera, K and Yanagihara, K and Nishino, T and Mukae, H and Izumikawa, K}, title = {Analysis of risk factors for long COVID after mild COVID-19 during the Omicron wave in Japan.}, journal = {Respiratory investigation}, volume = {63}, number = {3}, pages = {303-310}, doi = {10.1016/j.resinv.2025.02.008}, pmid = {40048846}, issn = {2212-5353}, abstract = {BACKGROUND: Post-COVID-19 syndrome, referred to as "long COVID," is characterized by persistent symptoms that develop during or after SRAS-CoV-2 infection lasting for ≥12 weeks, which cannot be explained by factors other than COVID-19. Previous studies before the Omicron pandemic have identified female sex, older age (≥50 years), severity of illness, obesity, diabetes, and smoking as risk factors for long COVID. However, data on long COVID following the emergence of the Omicron variants are limited.

METHODS: An online survey was conducted among outpatients diagnosed with mild COVID-19 at 14 participating institutions in Japan between July 30, 2022, and December 31, 2023.

RESULTS: Of the included 246 cases, 76 (35.5%) experienced at least one long COVID symptom 12 weeks after onset. Logistic regression analysis revealed that age ≥40 years was significantly associated with an increased risk of respiratory (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.67-8.65) and neurologic symptoms (OR: 4.53, 95% CI: 1.84-11.13). Conversely, antiviral drug use was associated with a decreased risk of respiratory symptoms (OR: 0.31, 95% CI: 0.11-0.93).

CONCLUSION: Caution is warranted when treating patients over 40 years of age with mild COVID-19 due to their higher susceptibility to developing long COVID. Antiviral drugs may be beneficial in managing respiratory symptoms and mitigating disease severity.}, } @article {pmid40048542, year = {2025}, author = {Sariol, A and Perlman, S}, title = {Lung inflammation drives Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {387}, number = {6738}, pages = {1039-1040}, doi = {10.1126/science.adw0091}, pmid = {40048542}, issn = {1095-9203}, mesh = {*COVID-19/immunology/complications/virology ; Animals ; Mice ; *Lung/pathology/virology/immunology ; *Post-Acute COVID-19 Syndrome ; Peroxisomes/metabolism ; Macrophages/immunology ; Pneumonia/virology ; Humans ; Macrophages, Alveolar/virology/immunology ; Disease Models, Animal ; SARS-CoV-2/immunology ; }, abstract = {Peroxisome dysfunction in macrophages impairs lung repair after COVID-19 in mice.}, } @article {pmid40048451, year = {2025}, author = {Al Masoodi, WTM and Radhi, SW and Abdalsada, HK and Niu, M and Al-Hakeim, HK and Maes, M}, title = {Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0316373}, pmid = {40048451}, issn = {1932-6203}, mesh = {Humans ; Male ; Female ; *Insulin Resistance ; *COVID-19/metabolism/psychology/complications/blood ; *Fatigue Syndrome, Chronic/metabolism/virology/immunology/blood ; Middle Aged ; Adult ; *Signal Transduction ; *Inflammation/metabolism ; SARS-CoV-2 ; Galanin/metabolism ; C-Reactive Protein/metabolism/analysis ; Post-Acute COVID-19 Syndrome ; Depression/metabolism ; Dinoprostone/metabolism/blood ; }, abstract = {BACKGROUND: Patients with Long COVID (LC) often experience neuropsychiatric symptoms such as depression, anxiety, and chronic fatigue syndrome (CFS), collectively referred to as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance significantly contribute to the physio-affective phenome associated with LC.

METHODS: In a cohort of 90 individuals, categorized into those with and without LC, we evaluated, 3-6 months following acute SARS-CoV-2 infection, the correlations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA), and Fibro-Fatigue (FF) Rating Scale scores, and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), S100B and neuron-specific enolase (NSE).

RESULTS: HAMD, HAMA, FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B are all higher in people with LC compared to those without LC. The HAMD/HAMA/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) - oxygen saturation (SpO2) (PBT/SpO2 index) during the acute infectious phase. A combination of biomarkers explained a large part of the variance in CFS and affective scores (33.6%-42.0%), with GAL-GALR1 signaling, PGE2, and CRP being the top 3 most important biomarkers. The inclusion of the PBT/SpO2 index increased the prediction (55.3%-67.1%). The PBT/SpO2 index predicted the increases in GAL-GALR1 signaling.

CONCLUSION: These results indicate that the CFS and affective symptoms that are linked to LC are the consequence of metabolic aberrations, activated immune-inflammatory pathways, and the severity of inflammation during the acute phase of SARS-CoV-2 infection.}, } @article {pmid40046855, year = {2025}, author = {Perestiuk, V and Kosovska, T and Dyvoniak, O and Volianska, L and Boyarchuk, O}, title = {Vitamin D status in children with COVID-19: does it affect the development of long COVID and its symptoms?.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1507169}, pmid = {40046855}, issn = {2296-2360}, abstract = {INTRODUCTION: Long COVID is characterized by diverse symptoms persisting after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the immunomodulatory and neuroprotective properties of vitamin D, understanding its role in long COVID symptoms is of growing interest. This study aimed to determine vitamin D status in children with COVID-19 and assess its impact on the clinical course of disease and long COVID development.

METHODS: A prospective cohort study included hospitalized children with confirmed COVID-19, aged 1 month to 18 years, diagnosed between September 2022 and March 2024. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured upon hospital admission, and follow-up was done to identify long COVID symptoms.

RESULTS: In total, 162 hospitalized patients with COVID-19 were examined. Vitamin D deficiency was determined in 8.0%, insufficiency in 25.3%, and optimal levels in 66.7% of children with COVID-19. Vitamin D deficiency/insufficiency was observed in 73% of children over 6 years and 21.6% of children under 6 years of age. Comorbid conditions were 1.4 times more frequent in children with vitamin D insufficiency, with undernutrition and obesity playing the most significant roles (p = 0.0023, p = 0.0245, respectively). Serum 25(OH)D concentration depends on COVID-19 severity (p = 0.0405) and children with vitamin D deficiency/insufficiency had a longer hospital stay (4 vs. 3 days, p = 0.0197). The vitamin D status affected the median levels of neutrophils, lymphocytes, their ratio, prothrombin time, fibrinogen levels, and the frequency of increased immunoglobulins M and E levels. Among 134 children who agreed to follow up, 56 (41.8%) experienced long COVID symptoms, while 78 (58.2%) recovered fully. Long COVID was frequently observed in children with vitamin D deficiency/insufficiency (p = 0.0331). The odds of developing long COVID were 2.2 times higher (p = 0.0346) in children with vitamin D deficiency/insufficiency compared to those with optimal levels. Children with vitamin D deficiency/insufficiency more often exhibited neurological (80% vs. 41.9%, p = 0.0040) and musculoskeletal symptoms (16% vs. 0%, p = 0.0208).

CONCLUSION: The 25(OH)D concentrations in children with COVID-19 depended on their age. Comorbid conditions affect the vitamin D status in children with COVID-19. Vitamin D influenced the COVID-19 severity and duration of hospitalization. There was an increased risk of developing long COVID in children with vitamin D deficiency/insufficiency, and its impact on the development of neurological symptoms associated with long COVID was established.}, } @article {pmid40046430, year = {2024}, author = {Talkington, GM and Kolluru, P and Gressett, TE and Ismael, S and Meenakshi, U and Acquarone, M and Solch-Ottaiano, RJ and White, A and Ouvrier, B and Paré, K and Parker, N and Watters, A and Siddeeque, N and Sullivan, B and Ganguli, N and Calero-Hernandez, V and Hall, G and Longo, M and Bix, GJ}, title = {Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1465787}, pmid = {40046430}, issn = {1664-2295}, abstract = {One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.}, } @article {pmid40046291, year = {2025}, author = {Busse, M and Pallmann, P and Riaz, M and Potter, C and Leggat, FJ and Harris, S and Longman, AJ and Lowe, R and Edwards, A and Siriwardena, AN and Sevdalis, N and McRae, J and Fish, J and Sewell, B and Jones, F}, title = {Effectiveness of a personalised self-management intervention for people living with long covid (Listen trial): pragmatic, multicentre, parallel group, randomised controlled trial.}, journal = {BMJ medicine}, volume = {4}, number = {1}, pages = {e001068}, pmid = {40046291}, issn = {2754-0413}, abstract = {OBJECTIVE: To evaluate the effectiveness of Listen, a self-management support intervention, for people living with long covid who were not in hospital.

DESIGN: Pragmatic, multicentre, parallel group, randomised controlled trial.

SETTING: Twenty four sites in England and Wales.

PARTICIPANTS: Identified from long covid clinic waiting lists, word of mouth, and adverts/social media self-referred to the trial, 554 adults with long covid were randomised to receive either the Listen trial intervention or NHS usual care.

INTERVENTIONS: The Listen intervention involved up to six one-to-one personalised sessions with trained healthcare practitioners and an accompanying handbook co-designed by people with lived experience and health professionals. Usual NHS care was variable, ranging from no access, access to mobile applications and resources, and to specialist long covid clinics.

MAIN OUTCOME MEASURES: The primary outcome was the Oxford participation and activities questionnaire (Ox-PAQ) routine activities scale score at three months assessed in the intention-to-treat population. Secondary outcomes included Ox-PAQ emotional wellbeing and social engagement scale scores, the Short Form-12 (SF-12) health survey, the fatigue impact scale, and the generalised self-efficacy scale at three months. The EuroQol five-dimension five-level (EQ-5D-5L) assessed health utility. Serious adverse events were recorded.

RESULTS: Between 27 May 2022 and 15 September 2023, 554 people with long covid (mean age 50 (standard deviation 12.3) years; 394 (72.4%) women) were randomly assigned. At three months, participants assigned to the intervention group reported small non-significant improvements in the primary outcome of capacity for daily activities as assessed by Ox-PAQ routine activities scale score (adjusted mean difference -2.68 (95% confidence interval (CI) -5.38 to 0.02), P=0.052) compared with usual NHS care. For the secondary outcomes, people receiving the intervention also reported significant improvements in mental health (Ox-PAQ emotional wellbeing -5.29 (95% CI -8.37 to -2.20), P=0.001; SF-12 2.36 (95% CI 0.77 to 3.96), P=0.004), reductions in fatigue (fatigue impact score -7.93 (95% CI -11.97 to -3.88), P<0.001), and increases in self-efficacy (generalised self-efficacy scale 2.63 (95% CI 1.50 to 3.75), P<0.001). No differences were found in social engagement (-2.07 (95% CI -5.36 to 1.22), P=0.218) or SF-12 physical health (0.32 (95% CI -0.93 to 1.57), P=0.612). No intervention related serious adverse events were reported.

CONCLUSIONS: The personalised self-management support intervention of the Listen trial resulted in non-significant short term improvements in routine activities when compared with usual care. Improvements in emotional wellbeing, fatigue, quality of life, and self-efficacy for people living with long covid were also reported. Physical health and social engagement were not affected by the trial intervention. The limited understanding of how much change is clinically meaningful in this population along with the unblinded design, the use of self-referral as a recruitment method and variable usual care may have introduced unintended bias and thus limits robust conclusions about this intervention. Further research is required to fully establish the impact of the intervention.

TRIAL REGISTRATION NUMBER: ISRCTN36407216, ISRCTN registry, registered 27 January 2022.}, } @article {pmid40046136, year = {2025}, author = {Zhou, B and Xu, Q and Li, S and Wang, J and Liu, J and Zhang, T and Qu, X and Wang, X and Zhang, L and Liu, X and Gu, J and Zhou, L and Chen, F and Zong, X and Niu, W and Wang, L}, title = {Impact of Omicron infection on childhood health: the Beijing long-COVID study.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1377745}, pmid = {40046136}, issn = {2296-2565}, mesh = {Humans ; Child ; Adolescent ; Male ; *COVID-19/epidemiology ; Female ; Prospective Studies ; *SARS-CoV-2 ; Beijing/epidemiology ; Surveys and Questionnaires ; Child Health/statistics & numerical data ; }, abstract = {PURPOSE: The aim of this prospective study was to assess the dynamic changes of persisting symptoms among children aged 6-18 years during 1-2 months after the Omicron infection based on the modified SBQ-LC in the Tongzhou cohort, Beijing.

METHODS: This study includes 4 serial surveys performed within January 7-9, January 14-16, January 21-23, and February 12-14 in 2023, respectively. The prediction of age and survey for eight domains in the Rasch 0-100 linear score was undertaken by generalized additive mixed model.

RESULTS: Total 1,536 children (median age: 13 years, boys: 49.9%) had completed questionnaires across 4 surveys. Information on 51 symptoms was collected, with each scored on a 4-point rating scale. Generally, the distribution of age with all domains followed the N-shaped geometry, and that of survey followed the inverse J-shaped geometry. The Rasch linear score hit the lowest level among children aged 6-8 years, and reached the peak among children aged 12-13 years. The scores of all domains sharply declined from the first to the third survey, and remained stable between the third and the fourth survey. At the fourth survey, 95.05 and 51.37% children still had one or more problems relating to breathing and mental health, respectively, and the percentage of rest six domains was reduced to less than 20%.

CONCLUSION: Our findings indicate the multifaceted impact of Omicron infection on childhood health, especially among children aged 12-13 years. Moreover, breathing and mental health related problems still persisted during 1-to-2-month Omicron infection period.}, } @article {pmid40046118, year = {2025}, author = {Hernández-Hernández, L and Obeso-Benítez, P and Serrada-Tejeda, S and Sánchez-Herrera-Baeza, P and Rodríguez-Pérez, MP and Pérez-de-Heredia-Torres, M and Martínez-Piédrola, RM and Martín-Hernández, J}, title = {Use of wearables to measure the effects of long COVID on activities of daily living and their relationship to perceived exertion, occupational performance, and quality of life.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1519204}, pmid = {40046118}, issn = {2296-2565}, mesh = {Humans ; *Quality of Life ; *Activities of Daily Living ; Male ; Female ; *COVID-19/psychology ; Middle Aged ; *Physical Exertion ; *Wearable Electronic Devices ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Work Performance ; Canada ; Aged ; }, abstract = {INTRODUCTION: This study introduces a novel approach to understanding the impact of long COVID symptoms on daily life by integrating wearable devices to assess their influence on physical and mental quality of life, as well as perceived performance and satisfaction in daily activities.

METHODS: By leveraging technology such as accelerometers and pulse oximeters alongside assessment tools like the SF-12 Health Survey, the Canadian Occupational Performance Measure, and the Borg Scale, this research provides a comprehensive analysis that advances the field of occupational therapy.

RESULTS: An analytical observational study with 10 participants with long COVID and 10 healthy controls revealed that individuals with long COVID took significantly longer to complete tasks such as setting the table, sweeping, and climbing stairs, compared to the control group. Participants with long COVID also reported higher perceived exertion during all activities, as well as significantly worse physical health-related quality of life and lower satisfaction and performance in daily activities. Notably, perceived exertion correlated with reduced physical quality of life and diminished satisfaction and accomplishment in occupational tasks.

DISCUSSION: These findings emphasize the critical need for occupational therapy interventions to reduce perceived exertion, which could improve physical quality of life and enhance performance and satisfaction in daily activities for individuals with long COVID.}, } @article {pmid40045527, year = {2025}, author = {Promsrisuk, T and Srithawong, A and Kongsui, R and Sriraksa, N and Thongrong, S and Kloypan, C and Muangritdech, N and Khunkitti, K and Thanawat, T and Chachvarat, P}, title = {Therapeutic Effects of Slow Deep Breathing on Cardiopulmonary Function, Physical Performance, Biochemical Parameters, and Stress in Older Adult Patients with Long COVID in Phayao, Thailand.}, journal = {Annals of geriatric medicine and research}, volume = {}, number = {}, pages = {}, doi = {10.4235/agmr.24.0175}, pmid = {40045527}, issn = {2508-4909}, abstract = {BACKGROUND: Long COVID poses significant challenges for older adult patients, affecting their cardiopulmonary function and overall well-being. This study aimed to investigate the effects of slow deep breathing exercises on cardiopulmonary function, physical performance, biochemical markers, oxidative stress, and stress levels in older adult patients with long COVID.

METHODS: Sixty older adult patients with long COVID were randomly assigned to an exercise group of 30 patients and a control group of 30 patients. The exercise group engaged in slow deep breathing exercises for 30 minutes, five times a week over a period of 8 weeks, while the control group maintained their usual activities. Cardiovascular parameters, heart rate variability (HRV), respiratory muscle strength (RMS), pulmonary function tests (PFT), physical performance, biochemical and oxidative stress markers, and stress levels were assessed at baseline, 4 weeks, and 8 weeks. Data were analyzed using one-way repeated measures ANOVA.

RESULTS: The exercise group showed significant reductions in cardiovascular parameters (systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, and heart rate). Additionally, RMS, PFT, and physical performance showed significant increases. Improvements were also observed in HRV, biochemical markers (fasting blood sugar and lipid profile), oxidative stress markers (catalase, superoxide dismutase, and malondialdehyde), and stress levels. In contrast, no significant changes were found in the control group.

CONCLUSION: Slow deep breathing exercises, as a non-pharmacological intervention, significantly improve cardiopulmonary function, physical performance, and various health markers in older adult patients with long COVID. This approach provides a valuable and accessible therapeutic option for this population.}, } @article {pmid40042223, year = {2025}, author = {Monte, AL and do Nascimento Faustino da Silva, JKT and de Oliveira, MD and Farah, BQ and Kanegusuku, H and de Almeida Correia, M and Ritti Dias, RM}, title = {Dropouts in exercise rehabilitation program in patients with Long COVID: A systematic review.}, journal = {American journal of physical medicine & rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1097/PHM.0000000000002719}, pmid = {40042223}, issn = {1537-7385}, abstract = {OBJECTIVE: To describe dropout rates, reasons, and factors associated with dropout during rehabilitation programs for patients with Long COVID.

DESIGN: A search was conducted in PubMed, Embase, and Web of Science. Clinical trials were included that involved exercise programs lasting at least 4 weeks and focused on Long COVID patients aged 18 or older of both sexes, reporting on dropouts and their reasons. The TESTEX scale assessed study quality. Data on patients, interventions, and dropout rates were extracted and presented as frequencies.

RESULTS: Twenty-three studies with 1,523 patients (mean age 53.0 ± 6.4 years, 51% female) were included. Overall, 14% (n = 216) of Long COVID patients dropped out. Reasons included health problems (23%), incomplete assessments (19%), loss of interest (16%), lack of adherence (7%), adherence to other interventions (4%), and 31% unreported. The dropout rate was significantly higher in 2020 compared to 2021 (p = 0.039), while no significant associations were observed between the dropout rate and other variables.

CONCLUSION: Exercise rehabilitation studies for Long COVID patients show a 14% dropout rate, with the most common reasons being health-related issues and incomplete assessments.}, } @article {pmid40042095, year = {2025}, author = {Yu, L and Lin, Y and Li, J and Deng, C and Zhang, R and Liu, A and Wang, L and Li, Y and Wei, X and Lu, D and Gao, W and Zheng, Y}, title = {Suspect Screening of Pharmaceuticals and Their Transformation Products (TPs) in Wastewater during COVID-19 Infection Peak: Identification of New TPs and Elevated Risks.}, journal = {Environmental science & technology}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.est.5c00125}, pmid = {40042095}, issn = {1520-5851}, abstract = {Pharmaceuticals and their transformation products (TPs) in wastewater are emerging contaminants that pose risks to ecosystems and human health. Here, a typical period marked by the easing of the "zero-COVID" policy in December 2022, resulting in unprecedented infections in China, was chosen to illustrate the environmental impact of pharmaceutical usage during the COVID-19 pandemic. A suspect screening workflow was developed to identify pharmaceuticals and transformation products (TPs) in wastewater influent and effluent from a wastewater treatment plant (WWTP) during the peak and postpeak periods of COVID-19, integrating medication recommendations and TPs' prediction. A total of 114 pharmaceuticals and TPs were identified (13 TPs were detected for the first time in WWTP) by using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Wastewater-based epidemiology analysis showed that the most predominant pharmaceuticals were nonsteroidal anti-inflammatory drugs. Interestingly, the consumption of propafenone increased after the infection peak, possibly linked to long COVID-19 symptoms. Risks were further evaluated based on concentration, detection frequency, and PMT (persistence, mobility, and toxicity) properties, revealing that TPs of aminopyrine, acetaminophen, etc. showed even greater ToxPi scores than their parent compounds. This study highlights the elevated risks posed by pharmaceutical discharge during epidemics and the necessity for TPs' monitoring.}, } @article {pmid40040864, year = {2025}, author = {Vandenbogaart, E and Figueroa, M and Winston, D and Cole, S and Bower, J and Hsu, JJ}, title = {Preliminary evaluation of a mindfulness intervention program in women with long COVID dysautonomia symptoms.}, journal = {Brain, behavior, & immunity - health}, volume = {44}, number = {}, pages = {100963}, pmid = {40040864}, issn = {2666-3546}, abstract = {BACKGROUND: The symptom burden for patients with Long COVID-associated dysautonomia is high, yet there are currently no effective treatments. Mindfulness programs reduce psychological and physical symptoms as well as inflammatory gene expression in a variety of medical conditions. The study aim was to evaluate the effect of a six-week mindfulness program in women with Long COVID dysautonomia symptoms.

METHODS: Using a single arm, pre- and posttest design, women aged 18-54 years with Long COVID and orthostatic intolerance suggestive of dysautonomia were recruited from a single center. Participants attended a standardized, six-week, virtual mindfulness program. An active stand test and 6-min walk test (6MWT) were performed at baseline and post-intervention. Self-reported measures of physical and mental health symptoms collected at baseline, post-intervention and 4 week follow up included the composite autonomic symptom score (COMPASS-31), perceived stress (PSS), anxiety (GAD7), depression (PHQ8), COVID-19 event specific distress (IES-R), fatigue (FSI), sleep (ISI), well-being (MHC-SF), resilience (CD-RISC 10), and quality of life (SF-20). The effects on conserved transcriptional response to adversity (CTRA) were examined by next-generation sequencing of dried whole blood samples.

RESULTS: Twenty participants were enrolled with a mean age of 39.9 years (range 21-52 years). No significant changes were observed for the active stand test or 6MWT. A significant reduction in insomnia severity (ISI: 16.6 vs. 13.6; p = 0.001) was observed post-intervention, but scores reverted toward baseline levels at 4-week follow-up. No significant improvements were seen in autonomic symptoms, anxiety, perceived stress, depression, well-being, or COVID-19 related distress. Pro-inflammatory CTRA gene expression decreased significantly from pre-to post-intervention (p = 0.004). Declines in CTRA gene expression were most significant among those with 3 COVID-19 positive events (p = 0.01), followed by 2 events (p = 0.04) and 1 event (p = 0.05). Declines in CTRA gene expression did not vary significantly as a function of recent illness, COVID-19 hospitalization, demographic characteristics, or general medical history.

CONCLUSION: A virtual, six-week mindfulness program may improve sleep quality in women with Long COVID dysautonomia. While no objective improvement in dysautonomia symptoms were observed, our findings suggest a favorable effect of the mindfulness intervention on inflammatory and antiviral biology with a decrease in CTRA gene expression. Nonetheless, the symptom burden in this population is very high, and more attention is needed to provide effective multi-modal clinical therapies to this population.}, } @article {pmid40040820, year = {2025}, author = {Gottlieb, M and Yu, H and Chen, J and Spatz, ES and Gentile, NL and Geyer, RE and Santangelo, M and Malicki, C and Gatling, K and Saydah, S and O'Laughlin, KN and Stephens, KA and Elmore, JG and Wisk, LE and L'Hommedieu, M and Rodriguez, RM and Montoy, JCC and Wang, RC and Rising, KL and Kean, E and Dyal, JW and Hill, MJ and Venkatesh, AK and Weinstein, RA}, title = {Differences in Long COVID severity by duration of illness, symptom evolution, and vaccination: a longitudinal cohort study from the INSPIRE group.}, journal = {Lancet regional health. Americas}, volume = {44}, number = {}, pages = {101026}, pmid = {40040820}, issn = {2667-193X}, abstract = {BACKGROUND: Although short-term outcomes of Long COVID have been described, longer-term physical and mental health outcomes of Long COVID are less well-established. This study sought to assess differences in long-term physical and mental health outcomes extending up to three years among those with current, resolved, and no Long COVID, as well as duration of Long COVID and vaccination status.

METHODS: This was a prospective, multisite, study of participants with SARS-CoV-2 infection from 12/7/2020-8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by Long COVID status (never-had, resolved, current), Long COVID duration and vaccination status.

FINDINGS: Of 3663 participants, 2604 (71.1%) never had Long COVID, 994 (27.1%) reported current Long COVID, and 65 (1.8%) reported resolved Long COVID. Compared to never having Long COVID, current Long COVID had lower/worse scores for Patient-Reported Outcomes Measurement Information System (PROMIS) version 29 Physical (7.8; 95% confidence interval [CI] 7.3-8.3) and Mental Health (9.4; 95% CI 8.8-10.1) and higher likelihood of moderate-to-high stress (adjusted odds ratio [aOR]: 2.0; 95% CI 1.6-2.4), moderate-to-high loneliness (aOR: 1.6; 95% CI 1.4-2.0), moderate-to-severe fatigue (aOR: 3.0; 95% CI 2.5-3.7), insufficient activity (aOR for Speedy Nutrition and Physical Activity Assessment ≤4: 0.6; 95% CI 0.5-0.7; aOR for Exercise Vital Sign ≤150 min/week: 0.7, 95% CI 0.6-1.0), and worse dyspnea (aOR: 5.0; 95% CI 4.3-5.8). Resolved Long COVID had lower scores for PROMIS Physical by 2.0 (95% CI 0.2-3.8) and Mental Health by 2.3 (95% CI 0.2-4.4) than the never-had-Long COVID cohort. Number of COVID-19 vaccinations was associated with better outcomes across all measures.

INTERPRETATION: Among participants followed up to 3 years after initial infection, those with current Long COVID had worse physical and mental health outcomes. The majority of those with Long COVID did not resolve, with less than 2% having resolved Long COVID. The resolved Long COVID cohort had moderately worse physical and mental health compared with those never-having-Long COVID. COVID-19 vaccination was associated with better outcomes.

FUNDING: Centers for Disease Control and Prevention.}, } @article {pmid40040433, year = {2025}, author = {Chu, L and Honzay, I}, title = {Prevalence and Correlates of Probable Anxiety and Depression among U.S. Individuals with Long COVID.}, journal = {The journal of mental health policy and economics}, volume = {28}, number = {1}, pages = {3-16}, pmid = {40040433}, issn = {1091-4358}, mesh = {Humans ; United States/epidemiology ; Female ; Prevalence ; Male ; Middle Aged ; *Depression/epidemiology ; Adult ; *COVID-19/epidemiology/psychology ; *Anxiety/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; Socioeconomic Factors ; Young Adult ; Adolescent ; }, abstract = {BACKGROUND: The enduring repercussions of long COVID have emerged as a distinct health concern, encompassing both physical and mental health challenges, such as symptoms indicative of anxiety and depression.

AIMS OF THE STUDY: This study primarily aims to assess the prevalence of mental health issues among individuals in the United States grappling with long COVID. Additionally, it seeks to quantify the correlations between long COVID and both probable anxiety and probable depression. The research also endeavors to unravel socio-economic mechanisms contributing to these correlations and explore potential disparities in these associations.

METHODS: Utilizing a nationally representative dataset from the Household Pulse Survey, this study employs the probit model to investigate the associations between long COVID and probable anxiety as well as probable depression. To ensure robustness, complementary techniques, including alternative models and measures, are employed. A mechanism analysis is incorporated to identify socio-economic mediators that contribute to probable anxiety and depression in individuals with long COVID. Subgroup analyses explore variations in these associations across diverse groups.

RESULTS: Individuals with long COVID show a significantly higher prevalence of probable anxiety and depression compared to those without the condition. Through alternative techniques, the study confirms a significant correlation between long COVID and an increased likelihood of both probable anxiety and probable depression. Socio-economic mediators, specifically expense difficulty and concerns about job loss, significantly contribute to these associations. Additionally, females, individuals under 30, Hispanic individuals, non-Hispanic Black individuals, and those with disabilities are more likely to experience mental health challenges when dealing with long COVID.

DISCUSSION: The results offer quantitative evidence of a significant correlation between long COVID and mental health issues, emphasizing the critical need to address the challenges associated with prolonged COVID-19 symptoms. However, the study's reliance on a cross-sectional dataset underscores the importance of future research incorporating longitudinal data for a more comprehensive assessment of dynamic changes in mental health.

POLICY IMPLICATIONS: This study emphasizes the necessity for specialized mental health support programs tailored for individuals dealing with long COVID. Policymakers should consider adopting financial assistance measures and advocating for employers to accommodate those facing long COVID. Targeted mental health support and outreach initiatives are crucial for addressing the unique needs of at-risk populations and communities, mitigating the adverse consequences of long COVID on mental well-being and facilitating a return to pre-COVID-19 health trajectories.}, } @article {pmid40038650, year = {2025}, author = {Yang, H and Guan, L and Xue, Y and Li, X and Gao, L and Zhang, Z and Zhang, H and Ma, H and Liu, F and Huang, X and Tong, Z and Li, J}, title = {Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6-36 months after COVID-19.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {134}, pmid = {40038650}, issn = {1741-7015}, support = {82200007, 82070005, and 82270009//The National Natural Science Foundation of China/ ; 82200007, 82070005, and 82270009//The National Natural Science Foundation of China/ ; 2023YFC0872500//the Ministry of Science and Technology of the People's Republic of China/ ; BJRID2024-008 and BJRID2024-011//Beijing Research Center for Respiratory Infectious Diseases Project/ ; 2022-1-1061//Capital's Funds for Health Improvement and Research/ ; Ggyfz202401//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; }, mesh = {Humans ; *COVID-19 ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Prospective Studies ; Longitudinal Studies ; Adult ; *SARS-CoV-2 ; Proteomics/methods ; Aged ; Metabolomics ; Multiomics ; }, abstract = {BACKGROUND: Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood.

METHODS: We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs.

RESULTS: We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were significantly upregulated in COVID-19 convalescents. Pulmonary and molecular abnormalities persisted for 3 years in COVID-19 convalescents; impaired diffusing capacity for carbon monoxide (DLco) was the most prominent feature. We used this multi-omics profile to develop a model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) and two metabolites (arachidonoyl-EA and 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) for identification of COVID-19 convalescents with abnormal DLco.

CONCLUSIONS: These data provide insights concerning molecular sequelae among COVID-19 convalescents up to 3 years after hospital discharge, clarify mechanisms driving respiratory sequelae, and support the development of a novel model to predict reduced DLco. This longitudinal multi-omics analysis may illuminate the trajectory of altered lung function in COVID-19 convalescents.}, } @article {pmid40036243, year = {2025}, author = {Bullock, A and Dalton, AF and Stockwell, MS and McLaren, SH and Sano, E and Nguyen, HQ and Rao, S and Asturias, E and Lutrick, K and Ellingson, KD and Maldonado, Y and Mellis, AM and Smith-Jeffcoat, SE and Grijalva, CG and Talbot, HK and Rolfes, MAR and Biddle, JE and Zhu, Y and Ledezma, K and Pryor, K and Valdez de Romero, A and Vargas, C and Petrie, JG and Floris-Moore, M and Bowman, N}, title = {Ongoing Symptoms After Acute SARS-CoV-2 or Influenza Infection in a Case-Ascertained Household Transmission Study: 7 US Sites, 2021-2023.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf026}, pmid = {40036243}, issn = {1537-6591}, support = {/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days.

METHODS: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment. Participants completed a follow-up survey 90 days after enrollment to characterize ongoing symptoms.

RESULTS: We analyzed 1967 participants enrolled between December 2021 and May 2023. The risk of ongoing symptoms did not differ by infection status in SCV2 (SCV2-positive: 15.6%; SCV2-negative: 13.9%; odds ratio [OR]: 1.14; 95% CI: .7-1.69) or influenza (influenza-positive: 8.8%; influenza-negative: 10.0%; OR: .87; 95% CI: .45-1.72) households. However, among study participants with a documented infection, SCV2-positive participants had nearly twice the odds of ongoing symptoms as influenza-positive participants (OR: 1.92; 95% CI: 1.27-2.97).

CONCLUSIONS: These results suggest that SCV2 households have a significantly higher prevalence of ongoing symptoms compared with influenza households (OR: 1.78; 95% CI: 1.28-2.47). Among participants with SCV2 infection, underlying conditions (adjusted OR [aOR]: 2.65; 95% CI: 1.80-3.90) and coronavirus disease 2019 (COVID-19)-like symptoms (aOR: 2.92; 95% CI: 1.15-7.43) during acute infection increased odds of ongoing symptoms at 90 days, whereas hybrid immunity reduced the odds of ongoing symptoms (aOR: 0.44; 95% CI: .22-.90).}, } @article {pmid40034074, year = {2025}, author = {Kambič, T and Debevec, T and Lainscak, M}, title = {Can Intermittent Hypoxic Conditioning Enhance the Benefits of Standard Long COVID-19 Rehabilitation?.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {2}, pages = {e13769}, pmid = {40034074}, issn = {2190-6009}, support = {P5-0147//Slovenian Research and Innovation Agency/ ; P3-0456//Slovenian Research and Innovation Agency/ ; }, } @article {pmid40034063, year = {2025}, author = {Shahbazi, S and Shahbazi, E and Zayeri, F and Vahdat Shariatpanahi, Z}, title = {Early Administration of Bosentan in High-Risk COVID-19 Outpatients at Risk of Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Trial.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {2}, pages = {e13753}, pmid = {40034063}, issn = {2190-6009}, mesh = {Humans ; *Bosentan/therapeutic use ; *Sarcopenia/drug therapy ; Male ; Female ; *COVID-19/complications ; Aged ; Middle Aged ; *SARS-CoV-2 ; *COVID-19 Drug Treatment ; *Outpatients ; Double-Blind Method ; Endothelin Receptor Antagonists/therapeutic use/administration & dosage ; Treatment Outcome ; }, abstract = {BACKGROUND: Endothelial damage induces myofibrillar breakdown and muscle degradation in COVID-19 infection. There is a relationship between increased endothelin-1 synthesis and sarcopenia. We evaluated the preventive effect of early bosentan therapy as an endothelin receptor blocker in sarcopenia in high-risk outpatients with COVID-19 infection.

METHODS: From 15 December 2021 to 15 August 2023, patients within 3 days of the onset of signs and symptoms were randomly assigned to receive bosentan, 62.5 mg, or placebo, twice daily from enrollment for 30 days. The primary outcome was disease progression (death or hospitalization within 15 days after randomization), and the data for this outcome have been previously published. Sarcopenia as a secondary outcome was assessed prospectively at 3, 6, 9 and 12 months after randomization using the criteria of the Asian Working Group for Sarcopenia (AWGS) 2019 (IRCT.ir, IRCT20211203053263N1).

RESULTS: A total of 313 patients (156 bosentan group, 157 controls) were included in the analyses, which were performed under the intent-to-treat principle. Overall, the incidence of sarcopenia was 8.6% (n = 27). Nineteen (73%) had severe sarcopenia. At the 3-month follow-up, the incidence of sarcopenia was 8.3% in the total population, with the significant risk difference (RD) of -10.17% in the bosentan group versus the control group. The incidence in the total population and RD in the bosentan group versus the control group at months 6, 9 and 12 were 8.6% (RD: -10.81%, p < 0.001), 8.3% (RD: -10.17%, p = 0.001) and 5.4% (RD: -6.99%, p = 0.003), respectively. During the study, 29 people developed severe COVID-19 and were hospitalized. At follow-up, sarcopenia occurred in four inpatients and 23 outpatients (p = 0.23). Mortality occurred in 5.1% (n = 16) of the total population, including 4 (1.3%) of the patients in the bosentan group and 12 (3.8%) of the patients in the placebo group (p = 0.069). None of the patients who died had sarcopenia. Bosentan did not cause any severe adverse events and was well tolerated.

CONCLUSION: Early administration of bosentan may prevent sarcopenia in high-risk outpatients with COVID-19.}, } @article {pmid40032512, year = {2025}, author = {Valente Coronel, PM and Luiz Soares Basilio, DC and Teixeira Espinoça, I and Souza de Souza, KF and Miranda Campos, N and Seiji Nakano Ota, R and Paredes-Gamero, EJ and Wilhelm Filho, D and Coimbra Motta-Castro, AR and Trentin Perdomo, R and Parisotto, EB}, title = {Involvement of oxidative stress in post-acute sequelae of COVID-19: clinical implications.}, journal = {Redox report : communications in free radical research}, volume = {30}, number = {1}, pages = {2471738}, doi = {10.1080/13510002.2025.2471738}, pmid = {40032512}, issn = {1743-2928}, mesh = {Humans ; *Oxidative Stress ; *COVID-19/complications/blood ; Male ; Female ; Middle Aged ; *Biomarkers/blood ; *SARS-CoV-2 ; Adult ; Thiobarbituric Acid Reactive Substances/metabolism ; Peroxidase/blood/metabolism ; Post-Acute COVID-19 Syndrome ; Glutathione/blood/metabolism ; Inflammation/metabolism ; Superoxide Dismutase/blood/metabolism ; Cytokines/blood ; Catalase/blood/metabolism ; Uric Acid/blood ; Interleukin-6/blood ; gamma-Glutamyltransferase/blood/metabolism ; }, abstract = {Oxidative stress (OS) plays a key role in the pathophysiology of COVID-19 and may be associated with sequelae after severe SARS-CoV-2 infection. This study evaluated OS and inflammation biomarkers in blood from individuals with post-acute sequelae of COVID-19 (PASC). 64 male and female participants were distributed into three groups: healthy individuals (n = 20), acute COVID-19 patients (symptoms for <3 weeks, n = 15), and PASC patients (symptoms for >12 weeks, n = 29). Analyses included inflammatory cytokines, myeloperoxidase (MPO) activity, and OS markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), gamma-glutamyl transferase (GGT), reduced glutathione (GSH), uric acid (UA), thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC). Individuals with PASC showed increased IL-6 and IL-8. Both COVID-19 groups exhibited decreased SOD and CAT. GST decreased only in the acute group. Elevated GGT and GSH were found in the PASC group. High UA levels were observed in PASC individuals. There were no changes in TBARS values ⁣⁣in the PASC group. However, PC concentrations were elevated only in this group. Correlations were identified between inflammatory markers and OS parameters. These findings suggest that individuals with PASC pronounced OS, which potentially exacerbates disease complications. Monitoring OS biomarkers could aid in patient prognosis and management.}, } @article {pmid40030181, year = {2025}, author = {Granwehr, BP and , }, title = {CBT and rehabilitation improved long COVID symptoms.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/ANNALS-25-00369-JC}, pmid = {40030181}, issn = {1539-3704}, abstract = {GIM/FP/GP: [Formula: see text] Infectious Disease: [Formula: see text] Phys Med & Rehab: [Formula: see text].}, } @article {pmid40029778, year = {2025}, author = {Wang, J and Xiong, Y and Song, Z and Li, Y and Zhang, L and Qin, C}, title = {Progress in research on osteoporosis secondary to SARS-CoV-2 infection.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.12573}, pmid = {40029778}, issn = {2576-2095}, support = {2060204//State Key Laboratory Special Fund/ ; 2022B1111020005//Key-Area Research and Development Program of Guangdong Province/ ; 2021-I2M-1-034,2023-I2M-2-001//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 82221004//The Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; }, abstract = {The World Health Organization has declared that COVID-19 no longer constitutes a "public health emergency of international concern," yet the long-term impact of SARS-CoV-2 infection on bone health continues to pose new challenges for global public health. In recent years, numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to secondary osteoporosis. The mechanisms involved are related to the virus's direct effects on bone tissue, dysregulation of the body's inflammatory response, hypoxia, noncoding RNA imbalance, and metabolic abnormalities. Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis, current research is not comprehensive and in depth. Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism, elucidate the specific mechanisms of pathogenesis, and explore potential interventions. This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis, summarize the underlying mechanisms, and provide direction for future research.}, } @article {pmid40029146, year = {2025}, author = {Zhou, B and Zhang, Y and Han, S and Zhang, J and Song, L and Wang, H}, title = {Myocardial Dysfunction and Risk of Long COVID in Patients Recovered From Mild and Moderate COVID-19.}, journal = {Echocardiography (Mount Kisco, N.Y.)}, volume = {42}, number = {3}, pages = {e70120}, pmid = {40029146}, issn = {1540-8175}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Male ; Female ; Middle Aged ; *Echocardiography/methods ; SARS-CoV-2 ; Risk Factors ; Heart Ventricles/diagnostic imaging/physiopathology ; Adult ; Retrospective Studies ; Ventricular Dysfunction, Left/physiopathology/diagnostic imaging/etiology ; Cardiomyopathies/physiopathology/diagnostic imaging ; Severity of Illness Index ; Aged ; }, abstract = {PURPOSE: Numerous recovered COVID-19 patients exhibit persistent cardiovascular symptoms. However, the degree of myocardial dysfunction and its associated risk factors remain unclear. This study aims to evaluate myocardial dysfunction in recovered patients and pinpoint predictors of persistent cardiovascular symptoms.

METHODS: We reviewed the echocardiograms of patients who recovered from mild or moderate COVID-19 and presented with cardiovascular symptoms during the Omicron surge. Myocardial strain was analyzed in 546 patients before and after infection, and in 351 prepandemic healthy controls. Clinical follow-up at 12 months post-infection was used to evaluated symptom persistence, and multivariable logistic regression was used to identify independent predictors.

RESULTS: Baseline characteristics showed no significant differences between patients and controls (all p > 0.05). Although the left ventricle global longitudinal strain (LVGLS) remained stable post-infection, significant reductions emerged in regional left ventricle longitudinal strains (LVLS) and all left atrial strains (LAS) (all p < 0.05). Persistent cardiovascular symptoms affected 16.5% (90/546) of patients at 1-year follow-up. Multivariate analysis showed that only LA conduit strain (OR = 0.919, 95% CI: 0.857, 0.985, p = 0.017) and basal inferoseptal LVLS (OR = 0.883, 95% CI: 0.792, 0.986, p = 0.026) correlated with persisting cardiovascular symptoms.

CONCLUSION: Our findings demonstrate that subclinical but persistent COVID-19-associated myocardial dysfunction is characterized by regional LVLS impairment and LAS reduction. The identified strain parameters (LAScd and basal inferoseptal LVLS) serve as novel imaging markers for stratifying patients at risk of persistent cardiovascular symptoms. These results advocate for targeted echocardiographic surveillance and early intervention strategies in post-COVID care pathways.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06170307.}, } @article {pmid40027795, year = {2025}, author = {Sauter, KA and Webb, GM and Bader, L and Kreklywich, CN and Takahashi, DL and Zaro, C and McGuire, CM and Lewis, AD and Colgin, LMA and Kirigiti, MA and Blomenkamp, H and Pessoa, C and Humkey, M and Hulahan, J and Sleeman, M and Zweig, RC and Thomas, S and Thomas, A and Gao, L and Hirsch, AJ and Levy, M and Cherry, SR and Kahn, SE and Slifka, MK and Streblow, DN and Sacha, JB and Kievit, P and Roberts, CT}, title = {Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.18.638792}, pmid = {40027795}, issn = {2692-8205}, abstract = {Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.}, } @article {pmid40027165, year = {2025}, author = {Rus, CP}, title = {Disruptions in serotonin- and kynurenine pathway metabolism in post-COVID: biomarkers and treatment.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1532383}, pmid = {40027165}, issn = {1664-2295}, } @article {pmid40026747, year = {2025}, author = {Bansal, S and Giribabu, P and Sriganesh, K and Shukla, D}, title = {Perioperative outcomes in patients with symptomatic versus asymptomatic previous COVID-19 infection undergoing neurosurgical treatment (post-COVID-19 study).}, journal = {Journal of anaesthesiology, clinical pharmacology}, volume = {41}, number = {1}, pages = {98-105}, pmid = {40026747}, issn = {0970-9185}, abstract = {BACKGROUND AND AIMS: The long-term effects of coronavirus disease 2019 (COVID-19) infection (long-COVID) are being increasingly recognized. The long-COVID effects are more likely in individuals who were symptomatic than asymptomatic during their previous COVID-19 infection. The data on perioperative outcomes of patients undergoing elective neurosurgery long after their recovery from COVID-19 infection is lacking. The primary objective of this study was to compare the perioperative outcomes after elective neurosurgery between patients who were symptomatic and those who were asymptomatic during their previous COVID-19 infection. The secondary objectives were to compare the earlier COVID-19 characteristics and the perioperative pulmonary profile during current surgery between these groups.

MATERIAL AND METHODS: This prospective observational study was performed in adult patients undergoing elective neurosurgery with history of previous COVID-19 infection. Data was collected regarding previous COVID-19 infection (symptoms, hospitalization, treatment, complications, etc.) and current perioperative characteristics (pulmonary profile, perioperative complications, hospital stay, mortality, etc.).

RESULTS: A total of 50 patients were recruited during the study period, of which 35 (73%) patients were symptomatic during previous COVID-19 infection (two patients were excluded). The mean duration between current surgery and previous COVID-19 infection was 7 months. Patients symptomatic during earlier COVID-19 infection were females, older, and had a lower oxygen level during current surgery. There was no difference between symptomatic and asymptomatic groups in adverse perioperative outcomes such as desaturation, pulmonary or extrapulmonary complications, or non-extubation.

CONCLUSION: The perioperative outcomes of patients undergoing elective neurosurgery with previous mild to moderate symptomatic COVID-19 infection may not be different from those of patients with asymptomatic COVID-19 infection.}, } @article {pmid40025839, year = {2025}, author = {Hansen, KS and Jørgensen, SE and Cömert, C and Schiøttz-Christensen, B and Bross, P and Agergaard, J and Leth, S and Østergaard, L and Palmfeldt, J and Olsen, RKJ and Mogensen, TH}, title = {Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID.}, journal = {Journal of medical virology}, volume = {97}, number = {3}, pages = {e70275}, doi = {10.1002/jmv.70275}, pmid = {40025839}, issn = {1096-9071}, support = {//This study was supported by Aarhus County Research Initiative, Undine, Horizon Europe 2021, and Novo Nordisk Fonden. Novo Nordisk Foundation grants (NNF21OC0066984), (NNF21OC0067157), (NNF20OC0064890 (LØ, THM), Horizon Europe 2021 grant (HORIZON-HLTH-2021-857), (DISEASE-04-07), UNDINE grant 101057100 (THM), Danish Innovation Fund (PASCAL-MID (8056-00010B) (THM)), Danish National Research Foundation (DNRF164 (CiViA)), and Aarhus County Research Initiative (JP, RKJO)./ ; }, mesh = {Humans ; Male ; Female ; *Mitochondria/metabolism/genetics ; *COVID-19/metabolism/genetics/virology/pathology ; Middle Aged ; *Energy Metabolism ; Aged ; *Leukocytes, Mononuclear/metabolism/virology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/genetics ; Mitochondrial Diseases/genetics/metabolism ; Adult ; Whole Genome Sequencing ; Proteomics ; }, abstract = {Long COVID represents a significant global health challenge with an unclear etiology. Alongside accumulating evidence of mitochondrial dysfunction in patients with acute SARS-CoV-2 infection, a symptomatic overlap exists between long COVID and mitochondrial disorders. However, the genetic underpinnings of mitochondrial dysfunction in long COVID have not been previously explored. We employed whole genome sequencing to analyze 13 patients with severe long COVID to identify genetic defects related to mitochondrial function. We performed extracellular bioenergetics flux analysis on peripheral blood mononuclear cells and proteomics to evaluate cellular bioenergetics and compared the results to those of healthy controls. Our investigation identified 10 variants classified as pathogenic or likely pathogenic and 83 variants of unknown significance affecting a wide range of mitochondria-associated biological functions. Bioenergetics flux analysis in peripheral blood mononuclear cells revealed an altered ATP production rate in four long COVID patients compared to healthy controls. This study presents initial evidence of a potential underlying genetic predisposition to mitochondrial dysfunction in long COVID while demonstrating altered cellular energy capacity in a subset of these patients. These findings open avenues for further research into the role of mitochondrial dysfunction and pathology in patients suffering from long COVID and may pave the way for targeted therapeutic strategies aimed at mitigating mitochondrial dysfunction.}, } @article {pmid40022872, year = {2025}, author = {Ryu, T and Adler, BL and Jeong, SJ and Lee, DC and Hoke, A and Na, CH and Chung, T}, title = {Quantitative serum proteomic analysis for biomarker discovery in post-COVID-19 postural orthostatic tachycardia syndrome (PC-POTS) patients.}, journal = {Autonomic neuroscience : basic & clinical}, volume = {258}, number = {}, pages = {103247}, doi = {10.1016/j.autneu.2025.103247}, pmid = {40022872}, issn = {1872-7484}, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a chronic, debilitating condition that is characterized by an excessive increase in heart rate upon orthostatic challenge. Before the COVID-19 pandemic, POTS affected 0.5 % to 1 % of the U.S. population. Since the pandemic, the incidence has risen sharply, adding an estimated 6-7 million new cases in the U.S. Despite its importance, there is currently no reliable biomarker for POTS, leading to significant diagnostic delays. A major hurdle in identifying biomarkers is the heterogeneous nature of the syndrome. To address this, we focused on a homogeneous subgroup of post-COVID-19 POTS (PC-POTS) patients. We conducted quantitative proteomics on sera from 9 PC-POTS patients and 9 healthy controls, identifying 31 proteins with significantly different abundances in PC-POTS patients. Most elevated proteins were linked to actin filaments or immune functions/inflammation. Weighted Gene Co-Expression Network Analysis revealed module 7 (M7) correlated strongly with PC-POTS diagnosis and related traits. The key proteins in M7 included MTPN, TAGLN2, ADP-ribosylation factor 1, PDLIM1, PPIA, CNN2, LGALSL, TXN, TLN1, TUBA4A, IL4, TREML1, GP1BA, and, all highly correlated with these traits. Cell-type enrichment analysis revealed that M7 was highly associated with immune and neuronal cells. The main pathways identified in M7 included the integrin signaling pathway, blood coagulation, and glycolysis. These findings suggest that the key proteins in M7 could serve as biomarkers for PC-POTS. This study uses quantitative proteomics to identify potential biomarkers that differentiate PC-POTS patients from healthy controls, establishing a foundation for further research and validation.}, } @article {pmid40022456, year = {2025}, author = {Buettikofer, T and Maher, A and Rainbird, V and Bennett, M and Freene, N and Mitchell, I and Huang, HC and Gaughwin, P and Johnson, M and Paratz, J and Bissett, B}, title = {Consumer Experience of an Australian Multidisciplinary Long COVID Clinic That Incorporates Personalised Exercise Prescription: A Qualitative Analysis.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {28}, number = {2}, pages = {e70179}, pmid = {40022456}, issn = {1369-7625}, support = {//This study was supported by Canberra Hospital Private Practice Fund and Exercise and Sports Science Australia./ ; }, mesh = {Humans ; *COVID-19/therapy ; Australia ; *Qualitative Research ; Female ; Male ; Middle Aged ; *Exercise Therapy/methods ; Aged ; Adult ; Interviews as Topic ; SARS-CoV-2 ; Patient Satisfaction ; }, abstract = {BACKGROUND: In Australia, Long COVID is prevalent in 5%-10% of COVID-19 cases. Few multidisciplinary services exist to support recovery from Long COVID.

OBJECTIVE: To understand the consumer experience and acceptability of a novel Australian Long COVID Recovery Clinic, which incorporates personalised exercise prescription including respiratory and peripheral strengthening and carefully monitored cardiovascular training.

DESIGN: Qualitative study; semi-structured interviews conducted by a researcher external to the clinic delivery.

SETTING, PARTICIPANTS: A convenience sample of participants who have completed the Long COVID Recovery Clinic.

MAIN OUTCOME MEASURES: Major themes were identified by inductive thematic analysis.

RESULTS: Fifteen participants were interviewed. 14/15 (93%) participants described the clinic model as acceptable or highly acceptable. Five core themes were identified, including (1) encouraging staff and light-filled facilities support recovery; (2) supervised exercise and pacing improve confidence with exercise; (3) peer support and group therapy augments recovery; (4) other services augment Long COVID recovery, and (5) importance of GP involvement in connection with clinic participation. Suggestions for improvement included extending the duration of the clinic programme beyond 2 months, reducing wait times by increasing staffing levels and adjusting the clinic schedule to broaden access options.

CONCLUSIONS: The majority of participants found that the Long COVID Recovery Clinic, which incorporates both supervised exercise and pacing, is acceptable and would recommend it to others. From the consumer perspective, the Long COVID Recovery Clinic aids recovery alongside GP management through a combination of peer support and an individually tailored programme.

A consumer was a highly valued member of our research team. She has been involved in study design, analysis, and interpretation. She has also been involved in editing the manuscript and provided advice to ensure the language used in the manuscript is sensitive to a consumer audience. As our consumer meets the authorship guidelines, we have included her as an author in this manuscript. We also intend to include our consumers in the dissemination of these results when published (e.g., social media).

TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12622000719730.}, } @article {pmid40021627, year = {2025}, author = {Heydemann, L and Ciurkiewicz, M and Störk, T and Zdora, I and Hülskötter, K and Gregor, KM and Michaely, LM and Reineking, W and Schreiner, T and Beythien, G and Volz, A and Tuchel, T and Meyer Zu Natrup, C and Schünemann, LM and Clever, S and Henneck, T and von Köckritz-Blickwede, M and Schaudien, D and Rohn, K and Schughart, K and Geffers, R and Kaneko, MK and Kato, Y and Gross, C and Amanakis, G and Pavlou, A and Baumgärtner, W and Armando, F}, title = {Respiratory long COVID in aged hamsters features impaired lung function post-exercise with bronchiolization and fibrosis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2080}, pmid = {40021627}, issn = {2041-1723}, support = {14-76403-184//Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)/ ; 398066876/GRK 2485/2//Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture)/ ; }, mesh = {Animals ; *COVID-19/virology/pathology/physiopathology ; Male ; *SARS-CoV-2 ; *Lung/pathology/physiopathology ; Cricetinae ; *Disease Models, Animal ; *Pulmonary Fibrosis/physiopathology/pathology/virology ; *Physical Conditioning, Animal ; Mesocricetus ; Aging/physiology ; Post-Acute COVID-19 Syndrome ; Humans ; Pulmonary Alveoli/pathology/virology/physiopathology ; }, abstract = {Long-term consequences of SARS-CoV-2 infection affect millions of people and strain public health systems. The underlying pathomechanisms remain unclear, necessitating further research in appropriate animal models. This study aimed to characterize the trajectory of lung regeneration over 112 days in the male hamster model by combining morphological, transcriptomic and functional readouts. We demonstrate that in the acute phase, SARS-CoV-2 Delta-infected, male, aged hamsters show a severe impairment of lung function at rest. In the chronic phase, similar impairments persisted up to 7 weeks post-infection but were only evident after exercise on a rodent treadmill. The male hamster model recapitulates chronic pulmonary fibrotic changes observed in many patients with respiratory long COVID, but lacks extra-pulmonary long-term lesions. We show that sub-pleural and interstitial pulmonary fibrosis as well as alveolar bronchiolization persist until 112 dpi. Interestingly, CK8[+] alveolar differentiation intermediate (ADI) cells are becoming less prominent in the alveolar proliferation areas from 28 dpi on. Instead, CK14[+] airway basal cells and SCGB1A1[+] club cells, expressing cell proliferation markers, mainly populate alveolar bronchiolization areas at later time-points. We postulate that pulmonary fibrosis and SCGB1A1[+] club cell-rich areas of alveolar bronchiolization represent potential risk factors for other diseases in long-COVID survivors.}, } @article {pmid40021398, year = {2025}, author = {Lee, JS and Choi, Y and Joung, JY and Son, CG}, title = {Corrigendum to 'Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study' [The American Journal of Medicine. 138 (2025) 346-353/ PMID: 38331137].}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2025.02.013}, pmid = {40021398}, issn = {1555-7162}, } @article {pmid40021380, year = {2025}, author = {Hammer, S and Monaca, C and Hoelz, A and Tannheimer, M and Baumgart, SH and Dornieden, K and Lüttel, D and Rall, M and Müller, H}, title = {["Ultimately, you are on your own." A qualitative analysis of barriers to health care from the perspective of patients with long COVID].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.zefq.2025.01.006}, pmid = {40021380}, issn = {2212-0289}, abstract = {BACKGROUND: About 5% of the population are affected by post-infectious symptoms after a Sars-CoV-2-infection. Long COVID or a post-COVID-19 condition can affect all organ systems and lead to a complete need for care. 10-50% of patients meet the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Treatment recommendations have so far been limited to stress management and symptomatic, psychological or activity-enhancing measures (physical or exercise therapy). Initial studies of patients' perspectives indicate that both the recognition of the disease and the medical care for affected patients are insufficient.

METHOD: Since June 2023, patients with long COVID or their relatives have been able to report medical and social care experiences by telephone or using an online reporting form from the Techniker (TK) Health Insurance fund and the German Society for Patient Safety as part of a project funded by the German Federal Ministry of Health. From 1,216 reports received by December 2023, 264 representative cases were selected and evaluated using structuring and summarizing content analysis. The aim was to understand the experiences of those affected with barriers to health and social care and their consequences.

RESULTS: In the fourth year after the start of the pandemic, there is a lack of care structures and competence on the part of all care service providers, according to those affected. Special outpatient clinics for post-viral syndromes are either not accessible for the majority of participants or do not accept new patients or have waiting times of up to two years. Aside from the fact that there are currently no causally effective treatments for post-viral syndromes, 85% of those surveyed report that medical or social contacts are not sufficiently informed about the clinical picture. 80% of participants report that their symptoms are not acknowledged by employees in the health and social care sector, or they are considered a psychological issue. As a result, patients receive no or incorrect treatment and/or do not receive appropriate social care. 56% report a deterioration in their health status caused by prescribed or recommended examinations or treatments. The psychologization of post-viral symptoms is described as stigmatizing and considered the main cause of the precarious care situation of those affected by long COVID.

DISCUSSION: The study shows that there are currently no adequate care concepts and structures for post-infectious illnesses and that activating therapies, mostly in connection with the assumption of a psychosomatic origin, lead to significant malpractice. The finding that the majority of respondents feel weakened, ashamed or harmed by their physicians is particularly dramatic. The data also provide evidence of systematic stigmatization and discrimination against those affected. The generalizability of the results is limited.

CONCLUSIONS: To ensure adequate medical and social care for patients with long COVID, rapid training and further education of all those involved, the development and expansion of specific care offerings as well as a monitoring of health care provision are urgently needed.}, } @article {pmid40027369, year = {2024}, author = {Sharma, K and Patel, I and Parikh, R and Kalyani, M and Banker, K and Dhorajiya, D and M, A}, title = {Exploring in-hospital clinical outcomes among acute myocardial infarction patients with prior COVID-19 history.}, journal = {Journal of cardiovascular and thoracic research}, volume = {16}, number = {4}, pages = {275-280}, pmid = {40027369}, issn = {2008-5117}, abstract = {INTRODUCTION: Limited real-world data exist regarding cardiovascular outcomes in post-COVID-19 individuals following discharge, particularly within the Asian Indian population. This study aims to explore the association between prior COVID-19 history and in-hospital outcomes in acute myocardial infarction patients.

METHODS: Hospital database was searched for the patients who were diagnosed with Acute myocardial infarction (AMI) and were grouped according to absence (Group-A) or presence (Group-B) of history of severe COVID-19 hospitalization at least 3 months prior to the index event of AMI. Study primary endpoint was defined as major adverse cardiovascular events (MACE) comprising of Re-AMI, stroke, death (3P) and acute decompensated heart failure (4P), which were analyzed between these 2 study groups.

RESULTS: Of 10,581 consecutive patients of AMI, 5.33% (n=564/10,581) patients had prior history of severe SARS-CoV-2 hospitalization beyond 3 months of index AMI. Past severe Covid-19 patients presenting with AMI were more likely to be younger (59.12+11.23 years vs. 52.01+10.05 years) and younger than 40 years of age. Patients in Group B demonstrated a notably higher prevalence of diabetes, hypertension, higher Killip class, and lower presenting LVEF compared to Group A. In-hospital cardiac arrest, stroke, heart failure and all-cause death were significantly higher in Group B patients. Higher unadjusted odds ratio for in hospital death OR=5.78 (2.56-10.23), 3-P MACE OR=2.33 (1.23-8.65) and 4-P MACE OR=2.58 (1.36-5.43) were found in patients with prior history of COVID-19. After adjusting for comorbidities, the ratio for in-hospital MACE was found to be non-significant.

CONCLUSION: Conventional risk factors and presence of comorbidities in individuals with prior history of COVID-19 hospitalization increased the risk of both 3P and 4P MACE during AMI.}, } @article {pmid40020560, year = {2025}, author = {Megari, K and Thomaidou, E and Theodoratou, M and Kougioumtzis, G and Papadopoulou, S and Katsarou, DV and Argiriadou, E}, title = {Do gastrointestinal symptoms influence neurocognitive functioning in COVID-19 patients?.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {135}, number = {}, pages = {111147}, doi = {10.1016/j.jocn.2025.111147}, pmid = {40020560}, issn = {1532-2653}, abstract = {BACKGROUND AND OBJECTIVES: SARS-Cov-19 virus is known to attack multiple organ systems including the brain and as a result, numerous of these patients manifest neurocognitive disorders. Moreover COVID-19, causes gastrointestinal symptoms such as nausea and vomiting, abdominal pain, diarrhea or constipation, loss of appetite and weight loss and these symptoms have been linked to neurocognitive dysfunction. According to studies, COVID-19 patients who report gastrointestinal symptoms as the predominant manifestations, perform worse on neurocognitive tests than those who do not suffer from such symptoms. In this study, we examined whether hospitalized COVID-19 patients with gastrointestinal symptoms presented neurocognitive dysfunction.

MATERIALS AND METHODS: The study enrolled 92 COVID-19 patients, hospitalized for 6-20 days, who were divided into 2 groups: the gastrointestinal group (GI) (n = 44) who presented with predominant gastrointestinal symptoms such as anorexia, nausea, vomiting, diarrhea and abdominal pain and the group without GI symptoms, (nGI) (n = 48), who reported fever, fatigue and symptoms from the respiratory system as the main symptoms. Neurocognitive assessment was performed by questionnaires administered to all patients, three months after the first positive PCR test for COVID-19.

RESULTS: T-test was conducted for each test. Results revealed that patients with GI symptoms had significantly lower performance on neuropsychological functions such as complex scanning and long-term memory, visuospatial perception, executive function, verbal working memory and short-term memory, compared to patients without GI symptoms.

CONCLUSIONS: We found that there was a significant relationship between cognitive function and GI symptoms. This indicates that COVID-19 patients with GI symptoms may be at increased risk for developing deficits with their memory and other aspects of cognition.}, } @article {pmid40019823, year = {2025}, author = {Artemiadis, A and Tofarides, AG and Liampas, A and Ioannou, C and Christodoulou, K and Louka, R and Vavougios, G and Zis, P and Bargiotas, P and Hadjigeorgiou, G}, title = {Long-COVID from the perspective of neurologists at the outpatient clinic: A cross-sectional field study.}, journal = {Neurological research}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/01616412.2025.2472824}, pmid = {40019823}, issn = {1743-1328}, abstract = {OBJECTIVES: Approximately 25% of individuals experience various symptoms months after the COVID-19 infection and are referred to as having Long-COVID syndrome. The primary objective of this study was to identify the pattern of neuropsychiatric symptoms and their influence on psychological health, sleep quality, and overall well-being.

METHODS: In this cross-sectional study, Long-COVID patients reported on their symptoms by using a predefined list. The symptom patterns were examined using cluster analysis. The clustering groups were compared based on psychological health, sleep, and well-being scores obtained from structured questionnaires.

RESULTS: There were 40 females and 13 males, with a mean age of 54.1 ± 12.2 years. The most frequently reported symptoms were fatigue (94.3%), followed by anxiety (79.2%), myalgias (75.5%), and concentration difficulties (71.7%). Clustering analysis revealed two clusters separated by the number of cognitive, psychiatric, general neurologic, and somatic symptoms (i.e. high and low number). Patients within the high number cluster reported significantly more symptoms of depression, anxiety and stress, and worse quality of sleep than the low number cluster. Overall, 32 patients (60.4%) were found to have poor well-being. Reporting more than 17 symptoms (58.6% of patients) predicted poor well-being with a sensitivity of 37.5% and specificity of 95.2% (p = 0.011).

DISCUSSION: In this study, Long-COVID patients presenting at the outpatient neurologic clinic were clustered based on the number of symptoms instead of the nature of these symptoms. A higher number of symptoms were associated with poorer psychological health, sleep quality, and overall well-being.}, } @article {pmid40019816, year = {2025}, author = {Singh, J and Quon, M and Goulet, D and Keely, E and Liddy, C}, title = {The Utilization of Electronic Consultations (eConsults) to Address Emerging Questions Related to Long COVID-19 in Ontario, Canada: Mixed Methods Analysis.}, journal = {JMIR human factors}, volume = {12}, number = {}, pages = {e58582}, doi = {10.2196/58582}, pmid = {40019816}, issn = {2292-9495}, mesh = {Humans ; Ontario/epidemiology ; *COVID-19/epidemiology ; *Remote Consultation/statistics & numerical data ; Male ; Female ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Adult ; Primary Health Care/statistics & numerical data ; Aged ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long COVID is an often debilitating condition affecting millions of people. Its diverse clinical presentations make effective diagnosis and management at the primary care level difficult, while specialist services for long COVID face extensive wait times. An electronic consultation (eConsult) program in Ontario developed a long COVID specialist group to allow primary care providers (PCPs) prompt access to specialist advice for patients with long COVID.

OBJECTIVE: This study aims to assess patterns of service use, response times, impact, and clinical content of eConsult cases submitted to an eConsult long COVID specialist group in Ontario.

METHODS: This study is a mixed methods analysis of eConsults submitted by PCPs to the long COVID specialist group of 2 eConsult services (Champlain eConsult BASE and Ontario eConsult) between June 1, 2021, and July 31, 2022. Data sources included the use data collected automatically by the services, responses to a mandatory closeout survey, and the content of PCP questions and specialist responses (Champlain eConsult BASE service only). Clinical questions or responses were analyzed using 2 validated taxonomies. Descriptive statistics were used for survey responses and use data.

RESULTS: A total of 40 PCPs submitted 47 eConsults through Champlain eConsult BASE and 197 PCPs submitted 228 cases through Ontario eConsult. The median specialist response time was 0.6 (IQR 0.19-2.36; mean 1.7, SD 2.29) days. The 5 most common symptoms of long COVID were fatigue (14/47, 30%), dyspnea (7/47, 15%), cough (6/47, 13%), altered sense of smell (ie, anosmia and parosmia; 6/47, 13%), and cognitive changes (6/47, 13%). The five main question categories asked by PCPs were: (1) management of chronic symptoms of COVID-19, (2) need for additional work-up or follow-up testing, (3) community resources to support or manage patients with long COVID, (4) diagnostic clarification, and (5) guidance regarding COVID-19 vaccination.

CONCLUSIONS: The long COVID groups provided rapid access to a multispecialty service that facilitated the avoidance of unnecessary face-to-face referrals. An assessment of eConsults highlighted 5 common question types, providing insight into potential gaps in knowledge among PCPs that could help guide medical education and policy.}, } @article {pmid40018652, year = {2025}, author = {Jain, N and Shah, K and Chauhan, R and Gupta, A and Arora, P and Saxena, D and Mavalankar, D}, title = {Mapping of long COVID condition in India: a study protocol for systematic review and meta-analysis.}, journal = {Frontiers in rehabilitation sciences}, volume = {6}, number = {}, pages = {1419963}, pmid = {40018652}, issn = {2673-6861}, abstract = {BACKGROUND: The COVID-19 pandemic has reported significant alarming aftereffects experienced by some individuals following acute sequelae of SARS-CoV-2 infection, commonly referred to as long COVID. Long COVID is a set of symptoms that remain for weeks or months, after the initial phase of COVID-19 infection is ended.

OBJECTIVE: This study protocol outlines the methodology of a systematic review followed by a meta-analysis to comprehensively assess the chronic effects of COVID-19 infection on the Indian population and determine the likely risk factors connected to the development and persistence of long COVID.

METHODOLOGY: This study will employ comprehensive search through a custom-made search strategy across significant databases (PubMed, MEDLINE etc.) and grey literature to identify related literature from January 2020 to December 2023. A systematic review and meta-analysis will be conducted to synthesize data from various studies. The data synthesis will involve a comprehensive narrative and tabular presentation of outcome data from included studies, focusing on long-term effects of COVID-19 infection in Indian population. A meta-analysis will be conducted contingent upon the availability and suitability of data. If sufficient and comparable quantitative data are identified across the included studies, statistical synthesis will be undertaken. Subgroup and sensitivity analyses will manage confounders, while MedCalc software will facilitate a meta-analysis to assess pooled data. Publication bias will be evaluated using statistical tests to ensure the integrity of the findings. In the absence of adequate data, a narrative synthesis will be performed to summarize the findings systematically and transparently.

CONCLUSION: The anticipated findings will contribute to a refined understanding of this condition and its lingering symptoms, guiding healthcare interventions and future research endeavors to mitigate the impact of long COVID in the Indian population.}, } @article {pmid40018183, year = {2024}, author = {Eccles, JA and Cadar, D and Quadt, L and Hakim, AJ and Gall, N and , and Bowyer, V and Cheetham, N and Steves, CJ and Critchley, HD and Davies, KA}, title = {Is joint hypermobility linked to self-reported non-recovery from COVID-19? Case-control evidence from the British COVID Symptom Study Biobank.}, journal = {BMJ public health}, volume = {2}, number = {1}, pages = {e000478}, pmid = {40018183}, issn = {2753-4294}, abstract = {OBJECTIVES: This study sought to explore whether generalised joint hypermobility (GJH, a common marker of variant connective tissue) was a risk factor for self-reported non-recovery from COVID-19 infection.

DESIGN: Prospective observational study.

SETTING: COVID Symptom Study Biobank (https://cssbiobank.com/) UK.

PARTICIPANTS: Participants were surveyed in August 2022. 3064 (81.4%) reported at least one infection with COVID-19. These individuals self-reported on recovery and completed a self-report questionnaire to detect GJH (Hakim and Grahame 5-part questionnaire, 5PQ).

MAIN OUTCOME MEASURES: The primary outcome was the presence of self-reported non-recovery from COVID-19 infection at the time of the survey. Additional outcomes included scores on 5PQ and self-reported fatigue level (Chalder Fatigue Scale).

RESULTS: The presence of GJH was not specifically associated with reported COVID-19 infection risk per se. However, it was significantly associated with non-recovery from COVID-19 (OR 1.43 (95% CI 1.20 to 1.70)). This association remained after sequential models adjusting for age, sex, ethnic group, education level and index of multiple deprivation (OR 1.33 (95% CI 1.10 to 1.61)) and further adjustment for vaccination status and number of vaccinations (OR 1.33 (95% CI 1.10 to 1.60)). Additionally, including in a model adjusting for all covariates, hypermobility significantly predicted higher fatigue levels (B=0.95, SE=0.25, t=3.77, SE, p=0.002). Fatigue levels mediated the link between GJH and non-recovery from COVID-19 (estimate of indirect effect=0.18, 95% bootstrapped CI 0.08 to 0.29).

CONCLUSIONS: Individuals with GJH were approximately 30% more likely not to have recovered fully from COVID-19 infection at the time of the questionnaire, and this predicted the fatigue level. This observation is clinically important through its potential impact for understanding and identifying sub-phenotypes of long COVID for screening and personalised targeted interventions. More generally, greater awareness of GJH and its extra-articular associations is needed for effective patient stratification and implementation of personalised medicine.}, } @article {pmid40017925, year = {2025}, author = {Rushyizekera, M and Delpierre, C and Makovski, TT and Coste, J}, title = {Occupational and non-occupational factors of post-COVID-19 condition: a cross-sectional survey in the French general working population.}, journal = {BMJ public health}, volume = {3}, number = {1}, pages = {e001613}, pmid = {40017925}, issn = {2753-4294}, abstract = {INTRODUCTION: Although the working population carries the greatest burden of long COVID, occupational and non-occupational factors of the condition have not yet been well documented in this population. The aim of this study was to investigate these factors.

METHODS: A nationwide random sampling cross-sectional survey was conducted among the adult population in mainland France after the large Omicron waves in the autumn of 2022. Post-COVID-19 condition (PCC) was defined according to the WHO. Associations of occupational and non-occupational factors with PCC were tested in a conceptual model accounting for the relationships between these factors and considering two control groups (previously infected participants without PCC and participants with no reported or diagnosed SARS-CoV-2 infection). Interactions between occupational and non-occupational factors were considered.

RESULTS: The survey included 1131 working adults. PCC was positively associated with reported infection while providing care (prevalence ratio (PR)=2.06 (95% CI 1.08 to 3.94)), being in contact with a colleague (PR=1.61 (95% CI 1.04 to 2.48)) and increased workload (PR=2.85 (95% CI 1.12 to 7.24)), whereas it was negatively associated with reported infection while being in contact with the public or clients (PR=0.23 (95% CI 0.07 to 0.76)). Several non-occupational factors were associated with PCC: sex, household size, household financial satisfaction, number of pre-existing chronic conditions, anxiety, injury sequelae and perceived SARS-CoV-2 infection severity. No interactions were found between these factors.

CONCLUSIONS: Reducing the burden of long COVID in the working population requires public health strategies that consider a wide spectrum of factors, including work conditions in a broad sense. Specific attention should be given to the most vulnerable workers accumulating such factors.}, } @article {pmid40015037, year = {2025}, author = {Jaiswal, S and Sahoo, S and Dhiman, V and Sachdeva, N and Singh, MP and Ram, S and Sharma, G and Bhadada, SK}, title = {Long COVID psychiatric sequelae, biochemical markers & tau protein: A 3-year follow-up study.}, journal = {Psychiatry research}, volume = {347}, number = {}, pages = {116413}, doi = {10.1016/j.psychres.2025.116413}, pmid = {40015037}, issn = {1872-7123}, abstract = {BACKGROUND: A significant percentage of COVID-19 survivors experience long-term neuropsychiatric and physical issues. Baseline biochemical parameters may be linked to these psychiatric sequelae.

AIM: This study aimed to explore the association between baseline biochemical parameters and psychiatric outcomes in COVID-19 survivors three years post-infection.

METHODS: We enrolled 100 COVID-19 survivors (mild and severe) and conducted comprehensive biochemical, endocrine, and psychiatric evaluations using peripheral blood samples and psychological assessments (GAD-7, PHQ-9, MoCA, ISI) at 3 years of follow-up assessment. Tau protein levels were measured at follow-up. Baseline biochemical data were retrieved from medical records, and linear regression analysis was used to identify predictors of psychiatric symptoms.

RESULTS: HbA1c levels were significantly higher in severe cases at baseline (7.08±2.11 vs. 6.22±1.62) and follow-up (6.54±2.01 vs. 5.78±1.07). Severe cases also had elevated p-tau protein levels (99.34±120 vs. 59.7 ± 45.9). Low sodium and potassium at baseline were negatively correlated with anxiety and depression scores, predicting anxiety (8 %) and depressive symptoms (6 %) in mild cases. Low calcium predicted depressive (10 %) and anxiety symptoms (7.5 %) across all cases.

CONCLUSION: COVID-19 survivors with a history of severe infection displayed higher p-tau and HbA1c levels, indicating potential new-onset diabetes and neuronal damage. Electrolyte imbalances, particularly sodium, potassium, and calcium, during acute infection predicted long-term psychiatric symptoms, including depression, anxiety, and somatization.}, } @article {pmid40014889, year = {2025}, author = {Bozic, I and Ivkic, D and Reinfried, L and Donath, J and Schmidt, C and Graf, S and Handschuh, P and Dold, M and Winkler, D and Naderi-Haiden, A and Praschak-Rieder, N and Rujescu, D and Weidenauer, A and Bartova, L}, title = {The role of esketamine in persistent long COVID with predominant psychiatric manifestations.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {93}, number = {}, pages = {66-67}, doi = {10.1016/j.euroneuro.2024.12.014}, pmid = {40014889}, issn = {1873-7862}, } @article {pmid40014600, year = {2025}, author = {O'Brien, KK and Brown, DA and McDuff, K and St Clair-Sullivan, N and Chan Carusone, S and Thomson, C and McCorkell, L and Wei, H and Goulding, S and O'Hara, M and Roche, N and Stokes, R and Kelly, M and Cheung, AM and Erlandson, KM and Harding, R and Vera, JH and Bergin, C and Robinson, L and Avery, L and Bannan, C and Torres, B and O'Donovan, I and Malli, N and Solomon, P}, title = {Episodic disability framework in the context of Long COVID: Findings from a community-engaged international qualitative study.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0305187}, pmid = {40014600}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *COVID-19/psychology/epidemiology ; Adult ; *Persons with Disabilities/psychology ; Middle Aged ; *Qualitative Research ; SARS-CoV-2/isolation & purification ; Canada/epidemiology ; United Kingdom/epidemiology ; United States/epidemiology ; Aged ; Ireland/epidemiology ; }, abstract = {BACKGROUND: Increasing numbers of adults are living with the health-related consequences of Long COVID. The Episodic Disability Framework (EDF), derived from perspectives of adults living with HIV, characterizes the multi-dimensional and episodic nature of health-related challenges (disability) experienced by an individual. Our aim was to determine the applicability of the Episodic Disability Framework to conceptualize the health-related challenges experienced among adults living with Long COVID.

METHODS: We conducted a community-engaged qualitative descriptive study involving online semi-structured interviews. We recruited adults who self-identified as living with Long COVID via collaborator community organizations in Canada, Ireland, United Kingdom, and United States. We purposively recruited for diversity in age, gender identity, ethnicity, sexual orientation, and time since initial COVID-19 infection. We used a semi-structured interview guide informed by the EDF to explore experiences of disability living with Long COVID, specifically health-related challenges and how challenges were experienced over time. We conducted a group-based content analysis.

RESULTS: Of the 40 participants, the median age was 39 years; and the majority were white (73%), women (63%), living with Long COVID for ≥ 1 year (83%). Consistent with the Episodic Disability Framework, disability was described as multi-dimensional and episodic, characterized by unpredictable periods of health and illness. Experiences of disability were consistent with the three main components of the Framework: A) dimensions of disability (physical, cognitive, mental-emotional health challenges, difficulties with day-to-day activities, challenges to social inclusion, uncertainty); B) contextual factors, extrinsic (social support; accessibility of environment and health services; stigma and epistemic injustice) and intrinsic (living strategies; personal attributes) that exacerbate or alleviate dimensions of disability; and C) triggers that initiate episodes of disability.

CONCLUSIONS: The Episodic Disability Framework provides a way to conceptualize the multi-dimensional and episodic nature of disability experienced by adults living with Long COVID. The Framework provides guidance for future measurement of disability, and health and rehabilitation approaches to enhance practice, research, and policy in Long COVID.}, } @article {pmid40014480, year = {2025}, author = {Wang, Z and Zhu, T and Li, X and Lai, X and Chen, M}, title = {Tragus Nerve Stimulation Attenuates Postural Orthostatic Tachycardia Syndrome in Post COVID-19 Infection.}, journal = {Clinical cardiology}, volume = {48}, number = {3}, pages = {e70110}, pmid = {40014480}, issn = {1932-8737}, support = {//This study was supported by Natural Science Foundation of Hunan Province (2019JJ50871, 2023JJ30745, 2024JJ4079)./ ; }, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/therapy/physiopathology ; Female ; Male ; *COVID-19/complications/therapy ; Adult ; Prospective Studies ; *Heart Rate/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; Electric Stimulation Therapy/methods ; }, abstract = {BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance and is frequently observed in post-COVID conditions.

OBJECTIVES: We conducted controlled, prospective, and randomized clinical trials to explore the potential therapeutic benefits of low-level tragus stimulation (LL-TS) in patients with POTS following COVID-19 infection.

METHODS: This study enrolled 57 participants with confirmed post-acute COVID-19 who had been diagnosed with POTS. The ear clip was attached to the right tragus of the patients for stimulation (20 Hz with a 1-ms duration) or sham stimulation. They were divided into two groups: the sham LL-TS group (sham stimulation, n = 26) and the LL-TS group (stimulation for 1 month, n = 31). LL-TS was performed 1 h twice daily for 1 month. Postural tachycardia was evaluated at baseline, 1-month visit, and 1-year visit. Heart rate variability (HRV) and plasma neuropeptide Y (NPY) were evaluated at respective time points.

RESULTS: The mean age of participants was 31.9 ± 7.2 years (61.4% female). LL-TS significantly attenuated the increase in heart rate from supine to a 10-min stand, as well as the average and maximum heart rates after 1 month of treatment. LL-TS also significantly reduced NPY levels. In addition, LL-TS significantly increased the high frequency (HF), but decreased the low frequency (LF) and LF/HF ratio during the postural test (all p < 0.01). These effects persisted during the 1-year follow-up.

CONCLUSION: LL-TS may be a promising therapeutic approach for attenuating autonomic imbalance in patients with POTS following COVID-19 infection.}, } @article {pmid40017858, year = {2023}, author = {Brown, M and Gerrard, J and McKinlay, L and Marquess, J and Sparrow, T and Andrews, R}, title = {Ongoing symptoms and functional impairment 12 weeks after testing positive for SARS-CoV-2 or influenza in Australia: an observational cohort study.}, journal = {BMJ public health}, volume = {1}, number = {1}, pages = {e000060}, pmid = {40017858}, issn = {2753-4294}, abstract = {OBJECTIVE: In a highly vaccinated Australian population, we aimed to compare ongoing symptoms and functional impairment 12 weeks after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection.

METHODS AND ANALYSIS: The study commenced on a positive PCR test for either COVID-19 or influenza in June 2022 during concurrent waves of both viruses. Participants were followed up 12 weeks later in September 2022 and self-reported ongoing symptoms and functional impairment. We conducted a multivariate logistic regression analysis, controlling for age, sex, First Nations status, vaccination status and socioeconomic profile.

RESULTS: There were 2195 and 951 participants in the COVID-19 and influenza-positive cohorts, respectively. After controlling for potential predictor variables, we found no evidence to suggest that adults with COVID-19 were more likely to have ongoing symptoms (21.4% vs 23.0%, aOR 1.18; 95% CI 0.92 to 1.50) or moderate-to-severe functional impairment (4.1% vs 4.4%, OR 0.81; 95% CI 0.55 to 1.20) at 12 weeks after their diagnosis than adults who had influenza.

CONCLUSIONS: In a highly vaccinated population exposed to the SARS-CoV-2 Omicron variant, long COVID may manifest as a postviral syndrome of no greater severity than seasonal influenza but differing in terms of the volume of people affected and the potential impact on health systems. This study underscores the importance of long COVID research featuring an appropriate comparator group.

TRIAL REGISTRATION NUMBER: ACTRN12623000041651.}, } @article {pmid40012912, year = {2024}, author = {Naiditch, H and Betts, MR and Larman, HB and Levi, M and Rosenberg, AZ}, title = {Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1376654}, pmid = {40012912}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; Kidney Diseases/immunology/virology/etiology ; Cytokines/metabolism/immunology ; }, abstract = {The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections' immunologic and inflammatory consequences beyond coronaviruses.}, } @article {pmid40012566, year = {2025}, author = {Goshi, N and Lam, D and Bogguri, C and George, VK and Sebastian, A and Cadena, J and Leon, NF and Hum, NR and Weilhammer, DR and Fischer, NO and Enright, HA}, title = {Direct effects of prolonged TNF-α and IL-6 exposure on neural activity in human iPSC-derived neuron-astrocyte co-cultures.}, journal = {Frontiers in cellular neuroscience}, volume = {19}, number = {}, pages = {1512591}, pmid = {40012566}, issn = {1662-5102}, abstract = {Cognitive impairment is one of the many symptoms reported by individuals suffering from long-COVID and other post-viral infection disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A common factor among these conditions is a sustained immune response and increased levels of inflammatory cytokines. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are two such cytokines that are elevated in patients diagnosed with long-COVID and ME/CFS. In this study, we characterized the changes in neural functionality, secreted cytokine profiles, and gene expression in co-cultures of human iPSC-derived neurons and primary astrocytes in response to prolonged exposure to TNF-α and IL-6. We found that exposure to TNF-α produced both a concentration-independent and concentration-dependent response in neural activity. Burst duration was significantly reduced within a few days of exposure regardless of concentration (1 pg/mL - 100 ng/mL) but returned to baseline after 7 days. Treatment with low concentrations of TNF-α (e.g., 1 and 25 pg/mL) did not lead to changes in the secreted cytokine profile or gene expression but still resulted in significant changes to electrophysiological features such as interspike interval and burst duration. Conversely, treatment with high concentrations of TNF-α (e.g., 10 and 100 ng/mL) led to reduced spiking activity, which may be correlated to changes in neural health, gene expression, and increases in inflammatory cytokine secretion (e.g., IL-1β, IL-4, and CXCL-10) that were observed at higher TNF-α concentrations. Prolonged exposure to IL-6 led to changes in bursting features, with significant reduction in the number of spikes in bursts across a wide range of treatment concentrations (i.e., 1 pg/mL-10 ng/mL). In combination, the addition of IL-6 appears to counteract the changes to neural function induced by low concentrations of TNF-α, while at high concentrations of TNF-α the addition of IL-6 had little to no effect. Conversely, the changes to electrophysiological features induced by IL-6 were lost when the cultures were co-stimulated with TNF-α regardless of the concentration, suggesting that TNF-α may play a more pronounced role in altering neural function. These results indicate that increased concentrations of key inflammatory cytokines associated with long-COVID can directly impact neural function and may be a component of the cognitive impairment associated with long-COVID and other post-viral infection disorders.}, } @article {pmid40011942, year = {2025}, author = {Leitzke, M and Roach, DT and Hesse, S and Schönknecht, P and Becker, GA and Rullmann, M and Sattler, B and Sabri, O}, title = {Long COVID - a critical disruption of cholinergic neurotransmission?.}, journal = {Bioelectronic medicine}, volume = {11}, number = {1}, pages = {5}, pmid = {40011942}, issn = {2332-8886}, abstract = {BACKGROUND: Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.

METHODS: This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[[18]F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN.

RESULTS: A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[[18]F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.

CONCLUSIONS: In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.}, } @article {pmid40011519, year = {2025}, author = {Hurme, A and Viinanen, A and Teräsjärvi, J and Jalkanen, P and Feuth, T and Löyttyniemi, E and Vuorinen, T and Kantele, A and Oksi, J and He, Q and Julkunen, I}, title = {Post-COVID-19 condition in prospective inpatient and outpatient cohorts.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6925}, pmid = {40011519}, issn = {2045-2322}, support = {5360-cc2fc//Jane ja Aatos Erkon Säätiö/ ; 3067-84b53//Jane ja Aatos Erkon Säätiö/ ; 26006205//Tampereen Tuberkuloosisäätiö/ ; 337530//Research Council of Finland/ ; 240045//Sigrid Juséliuksen Säätiö/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology/blood ; Male ; Female ; Middle Aged ; Prospective Studies ; *SARS-CoV-2/isolation & purification ; Aged ; Outpatients ; Inpatients ; Adult ; Risk Factors ; C-Reactive Protein/metabolism/analysis ; Post-Acute COVID-19 Syndrome ; Interleukin-6/blood ; }, abstract = {Viral persistence, immune dysregulation, hypocortisolism, and pulmonary tissue damage from acute infection are proposed as pathogenic mechanisms underlying post-COVID-19 condition (PCC). In this prospective observational study, we followed 62 COVID-19 inpatients and 53 COVID-19 outpatients for 24 months after the infection. During this period, we assessed prolonged symptoms, lung function, and a set of immunological markers and a proportion of the patient group was assessed with computed tomography three months post-infection. The prevalence of PCC, as assessed by four medical specialists, decreased from 51% at three months to 18% at 24 months. Risk factors included the severity of the acute infection and comorbidities of obstructive sleep apnea or obesity. Patients with PCC had higher serum levels of anti-SARS-CoV-2 S1 and N protein antibodies. In the whole group, spirometry results, orthostatic hypotension, or levels of soluble suppression of tumorigenicity 2, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), or cortisol had no association with PCC. However, using symptom clusters, patients with cognitive problems had lower cortisol levels, while patients with ongoing respiratory or myalgic symptoms had higher levels of IL-6 and hs-CRP. However, more extensive studies with clustering are needed to validate these results.}, } @article {pmid40011122, year = {2025}, author = {Chun, J and Lee, J and Matkin, K and Richard, C and Khan, U and Smedema, S}, title = {Bimodality in life satisfaction: The role of social support in individuals with long COVID.}, journal = {Disability and health journal}, volume = {}, number = {}, pages = {101813}, doi = {10.1016/j.dhjo.2025.101813}, pmid = {40011122}, issn = {1876-7583}, abstract = {BACKGROUND: Long COVID, characterized by persistent symptoms following SARS-CoV-2 infection, poses substantial challenges to individuals' physical and mental health, yet its impact on life satisfaction remains underexplored.

OBJECTIVE: This study aimed to investigate variations in life satisfaction among individuals with Long COVID and identify associated predictors using a mixture model approach.

METHODS: Participants (N = 212) were recruited via Prolific and completed surveys assessing life satisfaction, stress, resilience, social support, and hope. A mixture model analysis categorized participants into two clusters based on the relationship between life satisfaction and contributing factors (e.g., social support).

RESULTS: Cluster 1 (n = 153) exhibited lower life satisfaction scores, while Cluster 2 (n = 59) reported higher scores. Social support emerged as a significant predictor of life satisfaction in Cluster 2 (p < .001), with correlations indicating its positive association with life satisfaction and negative association with stress levels. However, social support was not significantly associated with life satisfaction in Cluster 1.

CONCLUSIONS: The findings highlighted the heterogeneous nature of life satisfaction among individuals with Long COVID. Social support, particularly from family and friends, was identified as a critical factor influencing well-being outcomes. Tailored interventions focusing on enhancing social support networks could mitigate the adverse impacts of Long COVID and improve overall quality of life for individuals with Long COVID.}, } @article {pmid40009958, year = {2024}, author = {McRae, S and Nielsen, G and McLoughlin, C and McWhirter, L and Davie, C and Vasquez, N and Carson, A and Stone, J and Hoeritzauer, I}, title = {Nonsurgical treatment of chronic idiopathic urinary retention: a scoping survey of physiotherapists' perspectives.}, journal = {Physiotherapy}, volume = {127}, number = {}, pages = {101460}, doi = {10.1016/j.physio.2024.101460}, pmid = {40009958}, issn = {1873-1465}, abstract = {BACKGROUND: Treatment for chronic idiopathic urinary retention often involves invasive or surgical inventions. Physiotherapy may have a range of non-invasive treatments to offer, but this is under studied.

PURPOSE: To survey healthcare professionals exploring their experience and understanding of non-surgical treatments for chronic idiopathic urinary retention.

MATERIALS AND METHODS: An online survey was conducted using purposive sampling to include healthcare professionals who see patients with chronic idiopathic urinary retention.

RESULTS: There were 100 responses with 20/100 (20%) answering the optional "specialist" questions. Ninety percent perceived that chronic idiopathic urinary retention occurred with other conditions. Perception of recovery was poor. Only 3/20 (15%) perceived that more than half of patients improve. Non-surgical interventions included: education, pelvic floor physiotherapy, biofeedback, and tibial nerve stimulation. There were moderate to high levels of interest in treating this condition but low levels of confidence in ability. Seventy percent (70/100) perceived a lack of support from referrers and multidisciplinary colleagues.

CONCLUSIONS: Health professionals were interested in treating chronic idiopathic urinary retention and perceived that physiotherapy had something to offer this patient group. The low reported levels of confidence in ability reflects the lack of supporting literature. CONTRIBUTION OF THE PAPER.}, } @article {pmid40009792, year = {2025}, author = {Ribeiro, HS and Burdmann, EA and Yu, L}, title = {Renal long COVID-19: an ongoing debate requiring robust evidence.}, journal = {Jornal brasileiro de nefrologia}, volume = {47}, number = {1}, pages = {e2025E001}, pmid = {40009792}, issn = {2175-8239}, } @article {pmid40007741, year = {2025}, author = {González-Quevedo, A and Valdés Sosa, PA and Machado Curbelo, C and Gutiérrez Gil, J}, title = {Editorial: NeuroCOVID. Insights into the clinical manifestations and pathophysiology.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1561314}, pmid = {40007741}, issn = {1664-2295}, } @article {pmid40006965, year = {2025}, author = {Lorenz, C and Frankenberger, R}, title = {Novel Oronasal Drainage for Long COVID: Proposed Mechanisms-Case Report.}, journal = {Viruses}, volume = {17}, number = {2}, pages = {}, pmid = {40006965}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/therapy ; *Drainage/methods ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Male ; Middle Aged ; Female ; }, abstract = {Long COVID, potentially emerging post COVID-19 infection, involves extreme health challenges. Based on current literature in the field, we propose a novel approach to Long COVID treatment based on epipharyngeal abrasive therapy targeting ostia of the oral and nasal mucosa, having been identified for the first time. The presented case report documents the application of innovative oronasal drainage (OND), a novel treatment integrating physiological, biochemical, and fluid mechanical components simultaneously. OND led to remarkable improvements and even remissions of various symptoms, along with enhanced hand blood circulation. While the case suggests potential efficacy in Long COVID therapy, acknowledging inherent limitations is essential and its impact needs further validation through clinical trials.}, } @article {pmid40005460, year = {2025}, author = {Altinsoy, C and Dikmen, D}, title = {How Are Brain Fog Symptoms Related to Diet, Sleep, Mood and Gastrointestinal Health? A Cross-Sectional Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {2}, pages = {}, pmid = {40005460}, issn = {1648-9144}, mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *COVID-19 ; Middle Aged ; *Affect/physiology ; Adult ; *Sleep Quality ; Gastrointestinal Diseases/physiopathology/etiology/psychology/complications ; Surveys and Questionnaires ; Diet/adverse effects ; Aged ; SARS-CoV-2 ; Cognitive Dysfunction/etiology/physiopathology ; Feeding Behavior/psychology/physiology ; }, abstract = {Background and Objectives: Brain fog, characterized by cognitive difficulties such as memory impairment, lack of focus, and mental fatigue, is a common symptom reported during recovery from COVID-19, particularly in long COVID cases. This study explores potential triggers such as sleep quality, mood, and gastrointestinal health and examines the link between adherence to the MIND diet and brain fog severity. Materials and Methods: A cross-sectional study was conducted between 1 July and 15 December 2022. The questionnaire assessed brain fog symptoms, dietary habits, sleep quality, mood, and gastrointestinal symptoms. Linear regression analysis examined the relationships between brain fog symptoms, demographic factors, sleep quality, MIND diet adherence, and gastrointestinal symptoms. Results: Brain Fog Scale (BFS) scores were significantly higher in individuals who had COVID-19 (p < 0.05) and even higher in those with reinfection. Women had higher BFS and Brain Fog Severity Score (BFSS), MIND Diet, The Gastrointestinal Symptom Rating Scale (GSRS), Brief Mood Introspection Scale (BMIS) Pleasant-Unpleasant scores (p < 0.05). BFS and BFSS were positively correlated with GSRS (p < 0.05), while no correlation was found with MIND diet adherence. A negative correlation was observed between BFS and Sleep Quality Scale (SQS) (p < 0.05), but this was not significant in regression (p = 0.367). GSRS, Pleasant-Unpleasant Dimension, and Arousal-Calm Dimension were significant predictors of BFS (R = 0.599, R[2] = 0.358, p < 0.01). Conclusions: This study identifies being female as a risk factor for brain fog symptoms, with women reporting higher BFS and BFSS scores. While sleep quality showed a negative correlation with brain fog symptoms, this relationship was not significant in the regression model, suggesting that other factors, such as mood and gastrointestinal symptoms, may play a more dominant role. However, adherence to the MIND diet showed no significant relationship with brain fog symptoms. These findings suggest that addressing mood and gastrointestinal health may be key to managing brain fog in long COVID.}, } @article {pmid40005421, year = {2025}, author = {Stefania, MN and Toma, C and Bondor, CI and Maria, RV and Florin, P and Adina, MM}, title = {Long COVID and Lung Involvement: A One-Year Longitudinal, Real-Life Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {2}, pages = {}, doi = {10.3390/medicina61020304}, pmid = {40005421}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Female ; Male ; Middle Aged ; Longitudinal Studies ; Aged ; *Post-Acute COVID-19 Syndrome ; *Lung Diseases, Interstitial/physiopathology ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Lung/diagnostic imaging/physiopathology ; Severity of Illness Index ; Adult ; Risk Factors ; }, abstract = {Background and Objectives: Long COVID as a condition typically manifests itself three months after the initial onset of SARS-CoV-2 infection, with symptoms persisting for a minimum of two months. The aim of the present research was to identify potential predictors of post-COVID-19 syndrome (long COVID-19) and to evaluate factors associated with the presence of post-COVID-19 interstitial lung disease and functional decline. Materials and Methods: 210 patients hospitalized for confirmed SARS-CoV-2 infections mild, moderate, severe, and critical form have been evaluated at 3, 6 and twelve months. Results: Among them only one has been with a suspicion of interstitial lung disease after one year, the rest had no change in the lung. No risk factor from the baseline/3-month or 6-month evaluations significantly influenced patients' status at 12 months. The longer the duration of hospitalization, the lower the FVC and DLCO were at 3 months, but the longer the duration of hospitalization, the higher the number of symptoms at 3 months and 6 months. In a multivariate linear regression analysis, the number of hospitalization days remained statistically significant only for the number of symptoms at 3 months and 6 months. Conclusions: Long COVID seems to be related to the severity of the initial disease, and among the most persistent. Post-COVID-19 interstitial lung disease does not seem to be a frequent entity, as in our study only 0.5% out of 210 patients had it.}, } @article {pmid40005051, year = {2025}, author = {Giacosa, A and Barrile, GC and Gasparri, C and Perna, S and Rondanelli, M}, title = {Positive Effect of Lecithin-Based Delivery Form of Curcuma and Boswellia Extracts on Irritable Bowel Syndrome After COVID-19 Infection.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/nu17040723}, pmid = {40005051}, issn = {2072-6643}, mesh = {Humans ; *Irritable Bowel Syndrome/drug therapy ; *Curcuma/chemistry ; *Boswellia/chemistry ; *Plant Extracts ; Female ; Male ; Pilot Projects ; Adult ; Middle Aged ; *Lecithins ; *COVID-19/complications ; Dysbiosis ; Dietary Supplements ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {Background: Post-COVID-19 irritable bowel syndrome (PCIBS) is a frequent finding and is frequently associated with enteral dysbiosis. This pilot study compared the effects of extracts from curcuma and boswellia on PCIBS and irritable bowel syndrome (IBS) in individuals who had never had a COVID-19 infection (controls). Methods: A total of 16 subjects with PCIBS and 28 controls with evidence of IBS gastrointestinal symptoms and with enteral dysbiosis were recruited and supplemented for 30 days with sunflower-lecithin-based formulations of extracts of Curcuma longa (500 mg) and Boswellia serrata (150 mg) b.i.d. and with low-FODMAP diet. Abdominal bloating, abdominal pain, enteral dysbiosis (as increased urinary indican), and the global assessment of efficacy (GAE) were evaluated at the end of the study. Results: In both cohorts, intra-cohort changes revealed a statistically significant (p < 0.05) reduction in bloating and abdominal pain. The GAE showed similar and relevant satisfactory rates in both groups. On the contrary, urinary indican values showed a significant decrease only in the IBS group. Conclusions: Supplementation with Curcuma and Boswellia has favorable effects on abdominal bloating and abdominal pain of subjects with PCIBS and with IBS, while enteral dysbiosis is significantly decreased only in patients with IBS. Additional studies are needed to confirm these preliminary findings and to clarify the reasons for the persistence of dysbiosis in PCIBS.}, } @article {pmid40005031, year = {2025}, author = {Arroyo-Romero, S and Gómez-Sánchez, L and Suárez-Moreno, N and Navarro-Cáceres, A and Domínguez-Martín, A and Lugones-Sánchez, C and Tamayo-Morales, O and González-Sánchez, S and Castro-Rivero, AB and Gómez-Sánchez, M and Rodríguez-Sánchez, E and García-Ortiz, L and Navarro-Matías, E and Gómez-Marcos, MA}, title = {Relationship Between Alcohol Consumption and Vascular Structure and Arterial Stiffness in Adults Diagnosed with Persistent COVID: BioICOPER Study.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/nu17040703}, pmid = {40005031}, issn = {2072-6643}, support = {RD21/0016/0010//Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS) is funded by the European Union-Next Generation EU, Facility for Recovery and Resilience (MRR)/ ; (GRS 2501/B/22)//The government of Castilla y León also collaborated with the funding of this study through the re-search projects/ ; CB22/06/00035//The CIBER CB22/06/00035 from the area of respiratory diseases/ ; }, mesh = {Humans ; Female ; *Vascular Stiffness ; Male ; Cross-Sectional Studies ; *COVID-19 ; *Alcohol Drinking/adverse effects/epidemiology ; Middle Aged ; Adult ; *Carotid Intima-Media Thickness ; Pulse Wave Analysis ; Carotid-Femoral Pulse Wave Velocity ; SARS-CoV-2 ; Cardio Ankle Vascular Index ; Aged ; Ankle Brachial Index ; Risk Factors ; }, abstract = {BACKGROUND: The relationship between alcohol consumption and vascular structure and arterial stiffness is not clear, especially in people diagnosed with persistent COVID. The aim of this study was to evaluate how alcohol use is related to vascular structure and arterial stiffness in adults with persistent COVID.

METHODS: A descriptive cross-sectional study was conducted involving 305 individuals (97 men and 208 women) diagnosed with persistent COVID according to the WHO criteria. Arterial stiffness was assessed by measuring the cardio-ankle vascular index (CAVI) and the brachial-ankle pulse wave velocity (ba-PWV) with a VaSera VS-1500 device, and the carotid-femoral pulse wave velocity (cf-PWV) with a Sphygmocor device. Vascular structure was assessed by measuring carotid intima-media thickness (c-IMT) with a Sonosite Micromax ultrasound unit. Alcohol intake was calculated using a standardized questionnaire and quantified in g/week.

RESULTS: Mean alcohol intake was 29 ± 53 g/week (men 60 ± 76 g/w and women 15 ± 27 g/w; p < 0.001). Heavy drinkers showed higher levels of c-IMT, cf-PWV, ba-PWV and CAVI than non-drinkers (p < 0.05). The multinomial regression analysis adjusted for sex and lifestyles showed a positive association between heavy drinking and c-IMT and cf-PWV values (β = 1.08 (95% CI 1.01-1.17); β = 1.37 (95% CI 1.04-1.80); ba-PWV and CAVI figures showed a similar trend, without reaching statistical significance.

CONCLUSIONS: The results of this study indicate that high alcohol use in patients with persistent COVID is linked to higher c-IMT and cf-PWV figures than in non-drinkers.}, } @article {pmid40004984, year = {2025}, author = {Suárez-Moreno, N and Gómez-Sánchez, L and Navarro-Caceres, A and Arroyo-Romero, S and Domínguez-Martín, A and Lugones-Sánchez, C and Tamayo-Morales, O and González-Sánchez, S and Castro-Rivero, AB and Rodríguez-Sánchez, E and García-Ortiz, L and Navarro-Matias, E and Gómez-Marcos, MA}, title = {Association of Mediterranean Diet with Cardiovascular Risk Factors and with Metabolic Syndrome in Subjects with Long COVID: BioICOPER Study.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, doi = {10.3390/nu17040656}, pmid = {40004984}, issn = {2072-6643}, support = {RD21/0016/0010//Instituto de Salud Carlos III (ISCIII)./ ; GRS 2501/B/22//The government of Castilla y León/ ; CB22/06/00035//The CIBER CB22/06/00035/ ; }, mesh = {Humans ; *Diet, Mediterranean ; *Metabolic Syndrome/epidemiology ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; *COVID-19/epidemiology/complications ; *Cardiovascular Diseases/epidemiology/etiology/prevention & control ; *Heart Disease Risk Factors ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, abstract = {BACKGROUND: Long COVID has been associated with increased cardiovascular risk and chronic low-grade inflammation, raising concerns about its long-term metabolic consequences. Given that the Mediterranean diet (MD) has shown beneficial effects on cardiovascular risk factors and inflammation in various populations, it is important to explore its potential impact on individuals with Long COVID. Therefore, the aim is to determine the association of the MD with cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in Caucasian subjects diagnosed with Long COVID.

METHODS: Cross-sectional study, 305 subjects diagnosed with Long COVID were included following the WHO criteria. Adherence to MD was evaluated with the MEDAS (Mediterranean Diet Adherence Screener) with 14 items used in Prevention with Mediterranean Diet study (PREDIMED study). The criteria considered to diagnose MetS were blood pressure, glycemia, triglycerides, HDL cholesterol, and waist circumference. Other CVRFs considered were tobacco consumption, total cholesterol, LDL cholesterol, body mass index, and baseline uric acid levels. The association between MD with CVRF and the number and components of MetS was analyzed using multiple regression models and multinomial regression.

RESULTS: The mean age was 52.75 ± 11.94 years (men 55.74 ± 12.22 and women 51.33 ± 11.57; p = 0.002), (68% women). The mean of the MEDAS questionnaire was 7.76 ± 2.37. The presented MetS were 23.6% (39.8% men and 15.9% women p < 0.001). In the multiple regression analysis, after adjusting for age and average time from acute COVID-19 infection to the date of inclusion in this study, the mean MD score showed a negative association with uric acid (β = -0.295; 95% CI: -0.496 to -0.093), BMI (β = -0.049; 95% CI: -0.096 to -0.002), the number of MetS components (β = -0.210; 95% CI: -0.410 to -0.010), and waist circumference (WC) (β = -0.021; 95% CI: -0.037 to -0.003) and a positive association with HDL cholesterol (β = -0.018; 95% CI: 0.001 to -0.037).

CONCLUSIONS: The findings of this study suggest that higher Mediterranean diet scores are associated with lower levels of uric acid, fewer MetS components, smaller waist circumference, and higher HDL cholesterol levels in individuals with Long COVID.}, } @article {pmid40004921, year = {2025}, author = {Tokumasu, K and Matsuki, N and Otsuka, Y and Sakamoto, Y and Ueda, K and Matsuda, Y and Sakurada, Y and Honda, H and Nakano, Y and Hasegawa, T and Takase, R and Omura, D and Otsuka, F}, title = {Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/jcm14041391}, pmid = {40004921}, issn = {2077-0383}, support = {JP23lk0310089 and JP24lk0310100//the Japan Agency for Medical Research and Development (AMED)/ ; }, abstract = {Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated.}, } @article {pmid40004799, year = {2025}, author = {Aliberti, A and Gasparro, R and Mignogna, M and Canfora, F and Spagnuolo, G and Sammartino, G and Coppola, N}, title = {Unveiling the Oral Lesions, Dysgeusia and Osteonecrosis Related to COVID-19: A Comprehensive Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/jcm14041267}, pmid = {40004799}, issn = {2077-0383}, abstract = {Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45-74%) and dysgeusia (32-59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues.}, } @article {pmid40004616, year = {2025}, author = {Fehrer, A and Sotzny, F and Kim, L and Kedor, C and Freitag, H and Heindrich, C and Grabowski, P and Babel, N and Scheibenbogen, C and Wittke, K}, title = {Serum Spike Protein Persistence Post COVID Is Not Associated with ME/CFS.}, journal = {Journal of clinical medicine}, volume = {14}, number = {4}, pages = {}, doi = {10.3390/jcm14041086}, pmid = {40004616}, issn = {2077-0383}, support = {//ME/CFS Research Foundation/ ; //Lost Voices Foundation/ ; }, abstract = {Background/Objectives: According to the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), an estimated 3-6% of people suffer from post-COVID condition or syndrome (PCS). A subset meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies have reported that SARS-CoV-2 proteins or RNA can persist after acute infection in serum or tissues, but their role in PCS is unclear. Methods: Here, SARS-CoV-2 spike protein was analyzed in the serum of 121 PCS patients with predominant fatigue and exertional intolerance, of whom 72 met diagnostic criteria for ME/CFS, 37 post-COVID recovered healthy controls, and 32 pre-pandemic healthy controls. Results: Spike protein was detected in the serum of 11% of recovered controls, 2% of PCS patients, and 14% of ME/CFS patients between 4 and 31 months after SARS-CoV-2 infection, but not in pre-pandemic samples. The occurrence and concentration of spike protein did not correlate with infection or vaccination timepoints. In ME/CFS patients, spike protein presence was not associated with the severity of symptoms or functional disability. In 5 out of 22 patients who under-went immunoglobulin depletion, spike protein levels were reduced or undetectable after treatment, indicating binding to immunoglobulins. Conclusions: In summary, this study identified serum spike protein in a subset of patients but found no association with ME/CFS.}, } @article {pmid40004244, year = {2025}, author = {Blankestijn, JM and Baalbaki, N and Beijers, RJHCG and Cornelissen, MEB and Wiersinga, WJ and Abdel-Aziz, MI and Maitland-van der Zee, AH and , }, title = {Exploring Heterogeneity of Fecal Microbiome in Long COVID Patients at 3 to 6 Months After Infection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, doi = {10.3390/ijms26041781}, pmid = {40004244}, issn = {1422-0067}, support = {LSHM20104; LSHM20068//Health Holland/ ; }, mesh = {Humans ; *COVID-19/microbiology/virology ; *Feces/microbiology/virology ; Male ; Female ; *Gastrointestinal Microbiome/genetics ; Middle Aged ; Aged ; *SARS-CoV-2/isolation & purification ; Adult ; Metagenome ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {An estimated 10% of COVID-19 survivors have been reported to suffer from complaints after at least three months. The intestinal microbiome has been shown to impact long COVID through the gut-lung axis and impact the severity. We aimed to investigate the relationship between the gut microbiome and clinical characteristics, exploring microbiome heterogeneity through clustering. Seventy-nine patients with long COVID evaluated at 3 to 6 months after infection were sampled for fecal metagenome analysis. Patients were divided into two distinct hierarchical clusters, based solely on the microbiome composition. Compared to cluster 1 (n = 67), patients in cluster 2 (n = 12) showed a significantly reduced lung function (FEV1, FVC, and DLCO) and during acute COVID-19 showed a longer duration of hospital admissions (48 compared to 7 days) and higher rates of ICU admissions (92% compared to 22%). Additionally, the microbiome composition showed a reduced alpha diversity and lower proportion of butyrate-producing bacteria in cluster 2 together with higher abundances of Ruminococcus gnavus, Escherichia coli, Veillonella spp. and Streptococcus spp. and reduced abundances of Faecalibacterium prausnitzii and Eubacteria spp. Further research could explore the effect of pre- and pro-biotic supplementation and its impact on lung function and societal participation in long COVID.}, } @article {pmid40004214, year = {2025}, author = {Hatayama, Y and Miyakawa, K and Kimura, Y and Horikawa, K and Hirahata, K and Kimura, H and Kato, H and Goto, A and Ryo, A}, title = {Identification of Putative Serum Autoantibodies Associated with Post-Acute Sequelae of COVID-19 via Comprehensive Protein Array Analysis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, doi = {10.3390/ijms26041751}, pmid = {40004214}, issn = {1422-0067}, support = {90015300//Takeda Science Foundation/ ; }, mesh = {Humans ; *COVID-19/immunology/blood/diagnosis ; *Autoantibodies/blood/immunology ; Male ; Middle Aged ; Female ; *SARS-CoV-2/immunology ; *Biomarkers/blood ; *Transcription Factors/immunology ; *Protein Array Analysis/methods ; Adult ; Retrospective Studies ; Homeobox Protein PITX2 ; F-Box Proteins/immunology ; Aged ; Homeodomain Proteins/immunology ; }, abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as "Long COVID", represents a significant clinical challenge characterized by persistent symptoms following acute COVID-19 infection. We conducted a comprehensive retrospective cohort study to identify serum autoantibody biomarkers associated with PASC. Initial screening using a protein bead array comprising approximately 20,000 human proteins identified several candidate PASC-associated autoantibodies. Subsequent validation by enzyme-linked immunosorbent assay (ELISA) in an expanded cohort-consisting of PASC patients, non-PASC COVID-19 convalescents, and pre-pandemic healthy controls-revealed two promising biomarkers: autoantibodies targeting PITX2 and FBXO2. PITX2 autoantibodies demonstrated high accuracy in distinguishing PASC patients from both non-PASC convalescents (area under the curve [AUC] = 0.891) and healthy controls (AUC = 0.866), while FBXO2 autoantibodies showed moderate accuracy (AUC = 0.762 and 0.786, respectively). Notably, the levels of these autoantibodies were associated with several PASC symptoms, including fever, dyspnea, palpitations, loss of appetite, and brain fog. The identification of PITX2 and FBXO2 autoantibodies as biomarkers not only enhances our understanding of PASC pathophysiology but also provides promising candidates for further investigation.}, } @article {pmid40003505, year = {2025}, author = {Jones, CL and Younger, J}, title = {Possible Racial Disparities in the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020280}, pmid = {40003505}, issn = {1660-4601}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/ethnology ; Male ; Female ; Middle Aged ; Adult ; Healthcare Disparities/ethnology ; Young Adult ; Patient Satisfaction ; Aged ; Surveys and Questionnaires ; }, abstract = {Myalgic encephalomyelitis (ME/CFS) a chronic, disabling illness with no established etiopathology. It has been indicated in some population-based studies that Black and ethnic minority populations are underdiagnosed with ME/CFS. The aims of the present study were to (1) identify the agreement between receiving an ME/CFS diagnosis and meeting diagnostic criteria, (2) identify the demographic characteristics associated with receiving a diagnosis, and (3) explore patient satisfaction with healthcare. Self-reported medical history and symptoms were collected via online survey from respondents with and without fatigue. The agreement between self-reporting an ME/CFS diagnosis and meeting the Center for Disease Control's (CDC) ME/CFS criteria or Institute of Medicine (IOM) criteria was assessed with Cohen's kappa. Patient characteristics predicting a physician diagnosis were analyzed with logistic regression. Associations between diagnosis, demographics, and healthcare satisfaction were assessed with chi-square tests of independence. There were 1110 responses. The agreement between meeting ME/CFS criteria and reporting an ME/CFS diagnosis was fair (CDC: κ = 0.29; SE = 0.02; IOM: κ = 0.28, SE = 0.03). White respondents had 2.94 greater odds of being diagnosed with ME/CFS than non-White respondents. Having an ME/CFS diagnosis was associated with dissatisfaction with healthcare (χ[2] (3, N = 1063) = 14.17, p = 0.003). The findings suggest racial disparities in the diagnostic processes for ME/CFS.}, } @article {pmid40003504, year = {2025}, author = {Pilkington, W and Bauer, BE and Doherty, IA}, title = {Living with Long COVID in a Southern State: A Comparison of Black and White Residents of North Carolina.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020279}, pmid = {40003504}, issn = {1660-4601}, support = {U54MD012392//National Institutes of Minority Health Disparities/ ; }, mesh = {Humans ; North Carolina/epidemiology ; *COVID-19/psychology/epidemiology ; Male ; Female ; Middle Aged ; *White People/statistics & numerical data ; Cross-Sectional Studies ; *Black or African American/psychology/statistics & numerical data ; Adult ; Aged ; Surveys and Questionnaires ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; White ; }, abstract = {Long COVID can devastate patients' overall quality of life, extending to economic, psychosocial, and mental health and day-to-day activities. Clinical research suggests that long COVID is more severe among Black and African American populations in the United States. This study examines the lived and lasting effects of long COVID among a diverse sample of North Carolina residents over one year by using three self-administered questionnaires completed online using Qualtrics. A cross-sectional descriptive analysis of the baseline results is presented. Our study recruited 258 adults, of which 51.5% had long COVID (but may have recovered), 32.3% had a COVID-19 infection at least once, and 16.3% had never had COVID-19. The socioeconomic status of Black participants was lower than that of White participants; however, the economic impact of long COVID was not worse. Across both groups, 64.4% were employed, 28.8% had to change tasks or work less, and 19.8% stopped working. Fewer White (32.6%) than Black (54.8%) participants always/often felt supported by family and friends about having long COVID. The majority of White participants (59.1%) reported that they did not recover from long COVID compared to 29.7% of Black participants. The long COVID/COVID-19 experience affected White and Black participants differently, but both populations continue feel the impacts.}, } @article {pmid40003501, year = {2025}, author = {Borges, FFDR and Braga, ACB and Viana, BS and Valente, J and Bemfica, JM and Sant'Anna, T and Goulart, CDL and Almeida-Val, F and Arêas, GPT}, title = {Functional Capacity Impairment in Long COVID After 17 Months of Severe Acute Disease.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020276}, pmid = {40003501}, issn = {1660-4601}, support = {EmergeSaude II PCTI 06/2020//Fundação de Amparo a Pesquisa do Estado do Amazonas/ ; }, mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; Case-Control Studies ; Middle Aged ; *Quality of Life ; Walk Test ; SARS-CoV-2 ; Adult ; Aged ; Heart Rate ; Dyspnea/physiopathology/virology ; Post-Acute COVID-19 Syndrome ; Muscle Strength ; Spirometry ; }, abstract = {Long COVID represents a significant challenge in understanding the prolonged impact of the disease. Despite its increasing recognition, detailed insights into the long-term cardiopulmonary consequences remain sparse. This study aimed to evaluate the functional capacity of individuals with persistent symptoms after severe COVID-19 infection compared to control individuals without symptomatic COVID or mild COVID after 17 months. This is a case-control study assessing 34 individuals divided into two groups regarding functional capacity by distance in a 6-min walk test (D6MWT) associated with gas analysis, spirometry, respiratory muscle strength, and quality of life. During the 6 MWT, an important lower heart rate (HR) was observed for the COVID group (106 ± 10 bpm, difference mean: 21.3; p < 0.001), with greater exertional perception (Borg dyspnea: 4.5 [2.0-9.0], p < 0.001 and Borg fatigue: 4.0 [2.0-7.0], p = 0.01), a significant decrease in the distance covered (416 ± 94 m, difference mean: 107; p = 0.002), and a low value of O2 uptake (V˙O2) (11 ± 5.0 mL/(kg min), difference mean: 8.3; p = 0.005) and minute ventilation (22 ± 8 L/min, difference mean: 18.6; p = 0.002), in addition to very low quality of life scores. Regression analysis showed a significant association between D6MWT and Borg fatigue and Borg dyspnea at rest (p = 0.003; p = 0.009). V˙O2 and HR were also significantly associated with the outcomes of the D6MWT (p = 0.04 and p = 0.004, respectively). In conclusion, individuals who have severe COVID-19 and persist with symptoms have low functional capacity, low V˙O2, low HR behavior, and low quality of life.}, } @article {pmid40003500, year = {2025}, author = {Smyth, NJ and Blitshteyn, S}, title = {Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020275}, pmid = {40003500}, issn = {1660-4601}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy ; *COVID-19/psychology ; Chronic Disease ; Language ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {People with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic disorders consistently report having difficulty obtaining effective and compassionate medical care and being disbelieved, judged, gaslighted, and even dismissed by healthcare professionals. We believe that these adversarial interactions and language are more likely to arise when healthcare professionals are confronting complex chronic illnesses without proper training, diagnostic biomarkers, or FDA-approved therapies. These problematic conversations between practitioners and patients often involve specific words and phrases-termed the "never-words"-can leave patients in significant emotional distress and negatively impact the clinician-patient relationship and recovery. Seeking to prevent these destructive interactions, we review key literature on best practices for difficult clinical conversations and discuss the application of these practices for people with Long COVID, ME/CFS, dysautonomia, and other complex chronic disorders. We provide recommendations for alternative, preferred phrasing to the never-words, which can enhance therapeutic relationship and chronic illness patient care via compassionate, encouraging, and non-judgmental language.}, } @article {pmid40003484, year = {2025}, author = {de Macêdo Rocha, D and Pedroso, AO and Sousa, LRM and Gir, E and Reis, RK}, title = {Predictors for Anxiety and Stress in Long COVID: A Study in the Brazilian Population.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {2}, pages = {}, doi = {10.3390/ijerph22020258}, pmid = {40003484}, issn = {1660-4601}, mesh = {Humans ; Brazil/epidemiology ; *COVID-19/psychology/epidemiology ; Female ; Male ; Adult ; *Stress, Psychological/epidemiology ; *Anxiety/epidemiology ; Middle Aged ; Cross-Sectional Studies ; SARS-CoV-2 ; Aged ; Young Adult ; }, abstract = {Anxiety and stress are major challenges for public health and represent significant symptoms in long COVID. Despite the repercussions on quality of life and mental health, their impacts have not been systematically consolidated in the Brazilian population. Our objective was to analyze the indicators and predictors of anxiety and perceived stress in people who have experienced long COVID in different regional contexts in Brazil. This cross-sectional survey was carried out in the five regions of Brazil and included 4239 adult individuals who had at least one diagnosis of COVID-19. Participants responded to questions on the Depression, Anxiety, and Stress Scale (DASS-21). The GAMLSS class of regression models estimated the predictors associated with the outcomes investigated. The results showed a predominance of participants with a single diagnosis of COVID-19 (65.4%), mild clinical conditions (89.5%), and high adherence to immunization strategies (98.4%). Overall, 48.5% of participants had residual symptoms that started between 4 and 12 weeks after the acute phase of COVID-19 infection. Positive screening for anxiety and perceived stress was associated with female gender, diagnosis of chronic diseases, presence of physical symptoms, moderate or severe clinical condition in the acute phase of the infection, and the need for hospitalization. Through this study, we confirmed that anxiety and stress, developed or exacerbated during the post-COVID-19 phase, represent significant challenges in the Brazilian population. Sociodemographic, clinical, and care conditions were predictors of the outcomes assessed. Knowing these repercussions can allow for personalizing mental health care and help structure evidence-based public policies.}, } @article {pmid40003283, year = {2025}, author = {Mercon, KR and Rose, AM and Cadham, CJ and Gebremariam, A and Pike, J and Wittenberg, E and Prosser, LA}, title = {Health Preferences in Transition: Differences from Pandemic to Post-Pandemic in Valuation of COVID-19 and RSV Illness in Children and Adults.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/children12020181}, pmid = {40003283}, issn = {2227-9067}, support = {U01IP001104/CC/CDC HHS/United States ; }, abstract = {Objective: This study aimed to measure changes in preferences regarding health-related quality of life associated with COVID-19 and RSV illness in children and adults from 2021 (during the COVID-19 pandemic) to 2023 (post-pandemic). Methods: A stated-preference survey elicited time trade-off (TTO) values from US adults in spring 2021 (n = 1014) and summer 2023 (n = 1186). Respondents were asked to indicate how much time they would hypothetically be willing to trade from the end of their life to avoid the effects of varying severities of COVID-19 and RSV illness for: (1) children; (2) parents of an ill child (family spillover); and (3) adults. Attitudes relating to COVID-19 vaccination and data on experience with COVID-19 or RSV illness were also collected. The primary outcome measure was the loss in quality-adjusted life years (QALYs). Changes in preferences over the time period from 2021 to 2023 were evaluated using regression analysis. Results: QALY losses increased with disease severity and were highest for Long COVID. Across all COVID-19 and RSV health states, QALY losses associated with child health states were higher than family spillover or adult health states. In the regression analysis, QALY losses reported in the 2023 survey were significantly lower than 2021 QALY losses for COVID-19, but not RSV. Conclusions: Preferences may change over time in a pandemic context and therefore, economic analyses of pandemic interventions should consider the timeframe of health preference data collection to determine whether they are suitable to include in an economic evaluation. Even with the impacts on health-related quality of life attenuated over time, childhood illnesses still had a measurable impact on caregivers' quality of life.}, } @article {pmid40002834, year = {2025}, author = {Whitaker-Hardin, B and McGregor, KM and Uswatte, G and Lokken, K}, title = {A Narrative Review of the Efficacy of Long COVID Interventions on Brain Fog, Processing Speed, and Other Related Cognitive Outcomes.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/biomedicines13020421}, pmid = {40002834}, issn = {2227-9059}, abstract = {In the years following the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, researchers have become acutely aware of long-term symptomology associated with this disease, often termed long COVID. Long COVID is associated with pervasive symptoms affecting multiple organ systems. Neurocognitive symptoms are reported by up to 40% of long COVID patients, with resultant effects of loss of daily functioning, employment issues, and enormous economic impact and high healthcare utilization. The literature on effective, safe, and non-invasive interventions for the remediation of the cognitive consequences of long COVID is scarce and poorly described. Of specific interest to this narrative review is the identification of potential interventions for long COVID-associated neurocognitive deficits. Articles were sourced from PubMed, EBSCO, Scopus, and Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published between the dates of January 2020 and 30 June 2024 were included in the search. Twelve studies were included in the narrative review, including a feasibility study, a pilot study, a case series, a case study, and an observational study, in addition to three randomized clinical trials and four interventional studies. Overall, treatment interventions such as cognitive training, non-invasive brain stimulation therapy, exercise rehabilitation, targeted pharmacological intervention, and other related treatment paradigms show promise in reducing long COVID cognitive issues. This narrative review highlights the need for more rigorous experimental designs and future studies are needed to fully evaluate treatment interventions for persistent cognitive deficits associated with long COVID.}, } @article {pmid40001603, year = {2025}, author = {Han, E and Müller-Zlabinger, K and Hasimbegovic, E and Poschenreithner, L and Kastner, N and Maleiner, B and Hamzaraj, K and Spannbauer, A and Riesenhuber, M and Vavrikova, A and Domanig, A and Nitsche, C and Lukovic, D and Zelniker, TA and Gyöngyösi, M}, title = {Circulating Autoantibodies Against Vasoactive Biomarkers Related to Orthostatic Intolerance in Long COVID Patients Compared to No-Long-COVID Populations: A Case-Control Study.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biom15020300}, pmid = {40001603}, issn = {2218-273X}, support = {KLI 1064-B//FWF Austrian Science Fund/ ; 21176//Medical Scientific Fund of the Mayor of the City of Vienna/ ; }, mesh = {Humans ; *COVID-19/immunology/blood/complications ; *Autoantibodies/blood/immunology ; Male ; Female ; Case-Control Studies ; *Biomarkers/blood ; Middle Aged ; *Orthostatic Intolerance/blood/immunology ; Aged ; *SARS-CoV-2/immunology ; Receptors, Adrenergic, beta-2/immunology ; Receptor, Endothelin A/immunology ; Receptor, Muscarinic M3/immunology ; Receptor, Angiotensin, Type 1/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item "Problems in performing usual activities".}, } @article {pmid40001244, year = {2025}, author = {Yuan, MQ and Song, L and Wang, ZR and Zhang, ZY and Shi, M and He, J and Mo, Q and Zheng, N and Yao, WQ and Zhang, Y and Dong, T and Li, Y and Zhang, C and Song, J and Huang, L and Xu, Z and Yuan, X and Fu, JL and Zhen, C and Cai, J and Dong, J and Zhang, J and Xie, WF and Li, Y and Zhang, B and Shi, L and Wang, FS}, title = {Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a randomized, double-blind, placebo-controlled trial.}, journal = {Stem cell research & therapy}, volume = {16}, number = {1}, pages = {94}, pmid = {40001244}, issn = {1757-6512}, support = {2022YFA1105604//Key Technologies Research and Development Program/ ; }, mesh = {Humans ; *COVID-19/therapy ; *Mesenchymal Stem Cell Transplantation/methods ; Male ; Female ; Double-Blind Method ; Middle Aged ; Follow-Up Studies ; *SARS-CoV-2 ; Adult ; Quality of Life ; Treatment Outcome ; Aged ; Mesenchymal Stem Cells/cytology ; }, abstract = {BACKGROUND: The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years.

METHODS: One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n = 65, 4 × 10[7] cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection.

RESULTS: Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 0.65-4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44-24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China's dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR = 0.54, 95% CI: 0.20-1.41).

CONCLUSIONS: These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102 .}, } @article {pmid40000709, year = {2025}, author = {Toufen, C and de Almeida, GC and Pompeu, JE and de Carvalho, CRF and de Carvalho, CRR}, title = {Neuroleptics used in critical COVID associated with moderate-severe dyspnea after hospital discharge.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6744}, pmid = {40000709}, issn = {2045-2322}, mesh = {Humans ; Male ; Female ; *Dyspnea/drug therapy ; *COVID-19/complications/epidemiology ; *Patient Discharge ; Aged ; Middle Aged ; *Antipsychotic Agents/therapeutic use ; SARS-CoV-2 ; Quality of Life ; Risk Factors ; COVID-19 Drug Treatment ; Critical Illness ; Prospective Studies ; Aged, 80 and over ; }, abstract = {Dyspnea is a prominent symptom in patients with long COVID due to its high prevalence and significant clinical impact. However, the influence of commonly used medications in critically ill patients on long-term dyspnea remains unclear. This study aimed to identify risk factors and assess the impacts associated with moderate to severe dyspnea in COVID-19 survivors. This study evaluated patients admitted to a university hospital between April 2020 and April 2021. Data were collected on clinical preconditions, hospital and ICU stays, and the use of corticosteroids, neuroleptics, neuromuscular blockers, midazolam, fentanyl, and noradrenaline. Post-discharge evaluations were conducted at 1 and 12 months, assessing dyspnea, frailty, quality of life, functional capacity, anxiety, and depression. Descriptive statistics, including frequencies and percentages, were used, and logistic regression analysis was performed to identify factors associated with moderate to severe dyspnea at 1 and 12 months post-discharge. Statistical significance was defined as P < 0.05. A total of 100 patients were prospectively included in the study; all underwent the 1-month evaluation, and 63 completed the 12-month evaluation. Limiting dyspnea, defined as an mMRC score > 1, was observed in 56.6% of patients at 1 month and 33.9% at 12 months post-discharge. Independent factors associated with limiting dyspnea at 1 month included the total dose of neuroleptics administered during hospitalization and the presence of pre-existing comorbidities. The use of corticosteroids, neuromuscular blockers, midazolam, fentanyl, and noradrenaline showed no significant association with limiting dyspnea. Dyspnea at 1 month post-discharge was an independent risk factor for the persistence of limiting dyspnea at 12 months. Patients with limiting dyspnea at 12 months exhibited higher levels of depression, anxiety, and frailty, alongside reduced quality of life and functionality. Patients with severe COVID-19 exhibit a high prevalence of limiting dyspnea in the long term. The total dose of neuroleptics administered during hospitalization and the presence of comorbidities were independently associated with limiting dyspnea after discharge. At 12 months post-discharge, individuals with persistent limiting dyspnea frequently demonstrated additional physical and mental health impairments, underscoring the need for comprehensive evaluation and management to mitigate the burden of long-term disabilities.}, } @article {pmid39997564, year = {2025}, author = {Lyons, CE and Alhalel, J and Busza, A and Suen, E and Gill, N and Decker, N and Suchy, S and Orban, Z and Jimenez, M and Perez Giraldo, G and Koralnik, IJ and Gill, MK}, title = {Non-Hospitalized Long COVID Patients Exhibit Reduced Retinal Capillary Perfusion: A Prospective Cohort Study.}, journal = {Journal of imaging}, volume = {11}, number = {2}, pages = {}, pmid = {39997564}, issn = {2313-433X}, support = {N/A//Research to Prevent Blindness/ ; N/A//Illinois Society to Prevent Blindness/ ; }, abstract = {The mechanism of post-acute sequelae of SARS-CoV-2 (PASC) is unknown. Using optical coherence tomography angiography (OCT-A), we compared retinal foveal avascular zone (FAZ), vessel density (VD), and vessel length density (VLD) in non-hospitalized Neuro-PASC patients with those in healthy controls in an effort to elucidate the mechanism underlying this debilitating condition. Neuro-PASC patients with a positive SARS-CoV-2 test and neurological symptoms lasting ≥6 weeks were included. Those with prior COVID-19 hospitalization were excluded. Subjects underwent OCT-A with segmentation of the full retinal slab into the superficial (SCP) and deep (DCP) capillary plexus. The FAZ was manually delineated on the full slab in ImageJ. An ImageJ macro was used to measure VD and VLD. OCT-A variables were analyzed using linear mixed-effects models with fixed effects for Neuro-PASC, age, and sex, and a random effect for patient to account for measurements from both eyes. The coefficient of Neuro-PASC status was used to determine statistical significance; p-values were adjusted using the Benjamani-Hochberg procedure. Neuro-PASC patients (N = 30; 60 eyes) exhibited a statistically significant (p = 0.005) reduction in DCP VLD compared to healthy controls (N = 44; 80 eyes). The sole reduction in DCP VLD in Neuro-PASC may suggest preferential involvement of the smallest blood vessels.}, } @article {pmid39997467, year = {2025}, author = {Ayyoub, S and Dhillon, NK and Tura-Ceide, O}, title = {Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms.}, journal = {Infectious disease reports}, volume = {17}, number = {1}, pages = {}, pmid = {39997467}, issn = {2036-7430}, support = {CP17/00114, CPII22/00006)//Miguel Servet type grants from the Institute of Health Carlos III/ ; PI21/01212//Catalan Pneumology Foundation (FUCAP) and from the Institute of Health Carlos III/ ; 2024 FI-3 00065//AGAUR-FI ajuts Joan Oró, backed by the Secretariat of Universities and Research of the Department of Research and Universities of the Generalitat of Catalonia, and the European Social Plus Fund/ ; R01HL1528322//NIH Funding/ ; }, abstract = {Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID.}, } @article {pmid39997269, year = {2025}, author = {Hatakeyama, J and Nakamura, K and Aso, S and Kawauchi, A and Fujitani, S and Oshima, T and Kato, H and Ota, K and Kamijo, H and Asahi, T and Muto, Y and Hori, M and Iba, A and Hosozawa, M and Iso, H}, title = {Effects of Long COVID in Patients with Severe Coronavirus Disease 2019 on Long-Term Functional Impairments: A Post Hoc Analysis Focusing on Patients Admitted to the ICU in the COVID-19 Recovery Study II.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {39997269}, issn = {2227-9032}, support = {JPMH21HA2011, JPMH23HA2011, JPMH24HA2015//MHLW, Research on Emerging and Re-emerging Infectious Diseases and Immunization/ ; }, abstract = {Background/Objectives: This study investigated the prevalence of functional impairments and the effects of long COVID on long-term functional impairments in patients with severe COVID-19. Methods: We conducted a nationwide multicenter cohort study in collaboration with nine hospitals, collecting data using self-administered questionnaires from participants aged 20 years or older who were diagnosed with COVID-19, admitted to the intensive care unit (ICU) between April 2021 and September 2021, and discharged alive. Questionnaires regarding daily life, sequela, and functional impairments were mailed to patients in August 2022. The effects of long COVID on functional impairments were examined using a multivariate logistic regression analysis. Results: The survey was completed by 220 patients, with a mean of 416 days after discharge. Among respondents, 20.5% had physical impairments (n = 45), 35.0% had mental disorders (n = 77), and 42.7% had either (n = 94). Furthermore, 77.7% had long COVID (171/220), and the most common symptom was dyspnea (40.0%). The multivariate analysis showed that fatigue/malaise, upper respiratory tract symptoms, myalgia, muscle weakness, decreased concentration, sleep disorder, brain fog, and dizziness were risk factors for functional impairments at one year. Conclusions: Many patients with severe COVID-19 admitted to the ICU still suffered from post-intensive care syndrome even after one year, which manifested in combination with direct symptoms of the original disease, such as long COVID.}, } @article {pmid39996021, year = {2025}, author = {Hung, LY and Wu, CS and Chang, CJ and Li, P and Hicks, K and Dibble, JJ and Morrison, B and Smith, CL and Davis, RW and Xiao, W}, title = {A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study.}, journal = {Frontiers in human neuroscience}, volume = {19}, number = {}, pages = {1509346}, pmid = {39996021}, issn = {1662-5161}, abstract = {This pilot study harnessed the power of network medicine to unravel the complex pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). By utilizing a network analysis on whole genome sequencing (WGS) data from the Severely Ill Patient Study (SIPS), we identified ME/CFS-associated proteins and delineated the corresponding network-level module, termed the SIPS disease module, together with its relevant pathways. This module demonstrated significant overlap with genes implicated in fatigue, cognitive disorders, and neurodegenerative diseases. Our pathway analysis revealed potential associations between ME/CFS and conditions such as COVID-19, Epstein-Barr virus (EBV) infection, neurodegenerative diseases, and pathways involved in cortisol synthesis and secretion, supporting the hypothesis that ME/CFS is a neuroimmune disorder. Additionally, our findings underscore a potential link between ME/CFS and estrogen signaling pathways, which may elucidate the higher prevalence of ME/CFS in females. These findings provide insights into the pathogenesis of ME/CFS from a network medicine perspective and highlight potential therapeutic targets. Further research is needed to validate these findings and explore their implications for improving diagnosis and treatment.}, } @article {pmid39995935, year = {2025}, author = {Nasir, SM and Yahya, N and Yap, KH and Manan, HA}, title = {Executive function deficit in patients with long COVID syndrome: A systematic review.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e41987}, pmid = {39995935}, issn = {2405-8440}, abstract = {BACKGROUND: Post-COVID-19 condition (Long COVID) refers to a condition in which patients endure persistent symptoms for more than 12 weeks, typically occurring at least 3 months after the onset of Coronavirus disease 2019 (COVID-19) infection. It occurs when a constellation of symptoms persists following the initial illness, and this may obstruct a daily routine and impose difficulty in life. Therefore, this study aimed to systematically review published articles assessing the neurocognitive profile of long COVID patients, with a specific emphasis on executive function (EF), and to determine the correlation between EF deficits and brain alterations through the utilisation of neuroimaging modalities.

METHODS: A thorough search was conducted using the PubMed/MEDLINE and Web of Science online databases following the PICOS and PRISMA 2020 guidelines. All included studies were deemed to be of high quality according to the Newcastle-Ottawa Scale (NOS).

RESULTS: A total of 31 out of 3268 articles were included in the present study. The main outcome is the proportion of individuals with cognitive deficits, particularly in the EF domain, as detected by neuropsychological assessments. The present study also revealed that EF deficits in long COVID patients are correlated with disruptions in the frontal and cerebellar regions, affecting processes such as nonverbal reasoning, executive aspects of language, and recall. This consistent disturbance also emphasised the correlation between EF deficits and brain alterations in patients with long COVID.

CONCLUSION: The present study highlights the importance of evaluating EF deficits in long COVID patients. This insight has the potential to improve future treatments and interventions.}, } @article {pmid39994668, year = {2025}, author = {Qin, M and Lee, K and Yoo, SJ}, title = {The impact of long COVID on heart rate variability: a cross-sectional study.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {261}, pmid = {39994668}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/physiopathology ; Cross-Sectional Studies ; *Heart Rate/physiology ; Male ; Female ; Adult ; *Autonomic Nervous System/physiopathology ; Middle Aged ; *SARS-CoV-2 ; Young Adult ; Electrocardiography ; Aged ; }, abstract = {BACKGROUND: Long-term COVID-19 (LC), which may affect the autonomic nervous system (ANS), is the term for the symptoms that some patients had for an additional month after contracting the virus. Therefore, during the LC phase, ANS status was evaluated in patients with mild-to-moderate COVID-19 using heart rate variability (HRV), a measurement of ANS function.

METHODS: A cross-sectional research with 173 participants - both positive and negative for COVID-19 - was conducted. Based on self-reports, patients with COVID-19 were classified as to whether they had LC or not. A 5-minute ECG recorder and data detection and response report were used to measure the ANS.

RESULTS: There were notable age differences across the groups (p = 0.034). Patients with LC under 25 years of age had a lower HRV categorized as a very-low-frequency (VLF) domain (p = 0.012). Compared to the group without LC, a higher number of people in the LC group had aberrant autonomic neuroactivity (p = 0.048).

CONCLUSION: Mild-to-moderate patients with COVID-19 in young to middle age may develop autonomic dysfunction one month after infection.}, } @article {pmid39994126, year = {2025}, author = {Datta, A}, title = {Assessing the effects of long-COVID on mental health in the United States: a population based study.}, journal = {Discover mental health}, volume = {5}, number = {1}, pages = {23}, pmid = {39994126}, issn = {2731-4383}, abstract = {BACKGROUND: While most individuals recover fully from COVID-19, a significant proportion of survivors experience prolonged symptoms lasting three months or more, a condition commonly referred to as long-COVID. Long-COVID conditions have been associated with reduced quality of life. By utilizing a nationally representative sample of nearly a million Americans, this study provides insights into the prevalence and impact of long-COVID on anxiety and depression in the U.S.

METHODS: We utilize the Household Pulse Survey data, which provides the first population-based sample on the prevalence of long-COVID, beginning with its June 2022 wave. This survey also includes questions on respondents' mental health status-specifically anxiety and depression. We employ a quasi-experimental difference-in-differences framework to conduct research using control groups, to predict anxiety and depression among individuals who suffered from long-COVID.

RESULTS: Approximately 51.8% of those surveyed tested positive for COVID-19 and of these 27.3% reported suffering from long-COVID. Individuals with long-COVID were twice as likely to experience anxiety and depression relative to those with mild/asymptomatic COVID-19. Our analysis at the sub-group level revealed that younger adults and females were disproportionately affected, reporting higher rates of anxiety and depression in both the COVID-19 and long-COVID groups. Additionally, individuals with lower income and educational attainment were more likely to experience mental health challenges. Relative to the reference group (Asians), Whites, Blacks, and Hispanics exhibited significantly higher odds of anxiety and depression in both groups. Notably, long-COVID was linked to a higher incidence of depression among males, which is consistent with previous research.

CONCLUSION: This study fills a significant gap in the literature regarding the mental health effects of long-COVID. The findings from this study provide strong evidence of the link between long-COVID and anxiety and depression, utilizing a large nationally representative sample, and employing rigorous analysis with control groups.}, } @article {pmid39993991, year = {2025}, author = {Mink, S and Wilhelm, F and Cadamuro, J and Reimann, P and Fraunberger, P}, title = {Anti-SARS-CoV-2 Antibodies in Long-COVID-Markers of Protection or Elevated Risk? A Systematic Review.}, journal = {Reviews in medical virology}, volume = {35}, number = {2}, pages = {e70027}, doi = {10.1002/rmv.70027}, pmid = {39993991}, issn = {1099-1654}, mesh = {Humans ; *COVID-19/immunology/prevention & control/virology ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests a potential link between antibody levels and long-COVID risk, findings remain inconclusive. Understanding antibody dynamics could support the identification of patients at risk, improve long-COVID diagnosis, and guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated the current literature on this topic. We therefore aimed to synthesise and evaluate existing evidence on the association between anti-SARS-CoV-2 antibody titres and long-COVID, with the goal of clarifying their potential role in predicting long-COVID risk, guiding patient management, and informing future research directions. Studies published in PubMed/Medline databases between January 2020 and October 2024 were included without language restrictions. Studies on body fluids other than serum/blood were excluded. Study selection and quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, and 7812 long-COVID patients, were included. Evidence was highly heterogenous but most studies reported an association between anti-SARS-CoV-2-spike antibodies and long-COVID, although the nature of the association appeared to be dependent on time from acute infection. Low anti-SARS-CoV-2-spike antibodies during acute COVID-19 were associated with increased risk of long-COVID. The association between low anti-SARS-CoV-2-spike antibodies during acute COVID-19 and long-COVID suggests that maintaining sufficiently high antibody levels may be protective. However, the current evidence level is low and further studies with sufficient power are required to confirm this association and to potentially determine protective cutoffs.}, } @article {pmid39993494, year = {2025}, author = {Saxon, M and Jackson, S and Seth, M and Koralnik, IJ and Cherney, LR}, title = {Cognitive rehabilitation improved self-reported cognitive skills in patients with Long COVID: An observational study.}, journal = {Archives of physical medicine and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.apmr.2025.02.009}, pmid = {39993494}, issn = {1532-821X}, abstract = {OBJECTIVE: To describe the effects of cognitive rehabilitation provided to patients with lingering cognitive difficulties or "brain fog" after COVID-19.

DESIGN: Retrospective cohort study SETTING: Outpatient rehabilitation setting PARTICIPANTS: Seventy consecutive patients with Long COVID that were referred from a Neuro-COVID clinic and evaluated and treated by speech-language pathologists INTERVENTIONS: Usual care cognitive rehabilitation MAIN OUTCOME MEASURES: Patients completed the Quality of Life in Neurological Disorders (NeuroQoL) Cognition Function Short Form and the Rivermead Behavioral Memory Test Story Recall assessments before and after treatment. Demographics, goals, treatment frequency/duration, and interventions were analyzed to determine treatment outcomes and patterns of care.

RESULTS: Of 70 patients, 83% were never hospitalized for COVID-19, the average age was 46.5 years, 77% were female and 69% were white. There were no differences in demographics, race, ethnicity or objective cognitive measures prior to starting treatment between the 50 individuals who completed their plan of care (POC) versus the 20 who did not. However, patients who did not complete their POC reported higher anxiety prior to treatment. Patients with higher anxiety prior to treatment demonstrated less improvement in cognitive quality of life measures following treatment. Of the 50 patients who completed their POC, 45 (90%) met all short-term goals. There was a significant increase in NeuroQoL Cognition Function scores from pre- to post cognitive rehabilitation in 36 patients tested, but no significant differences in objective measures of memory in 23 patients tested.

CONCLUSION: Cognitive rehabilitation resulted in self-reported improvement in functional cognition. However, anxiety limited the favorable impact of treatment and should be addressed in conjunction with cognitive therapy to maximize outcomes.}, } @article {pmid39991976, year = {2025}, author = {Erskine, F and Spensley, K and Prendecki, M and Santos, E and Anand, A and Altmann, D and Willicombe, M}, title = {The Effect of HLA Polymorphism on Immune Response to SARS-CoV-2 Vaccination Within an Infection-Naïve, Vulnerable Population With End-Stage Renal Disease.}, journal = {HLA}, volume = {105}, number = {2}, pages = {e70076}, pmid = {39991976}, issn = {2059-2310}, mesh = {Humans ; *Kidney Failure, Chronic/immunology/genetics ; *SARS-CoV-2/immunology ; *COVID-19/immunology/prevention & control/genetics ; *COVID-19 Vaccines/immunology ; Female ; Male ; Middle Aged ; *Polymorphism, Genetic ; *Alleles ; Aged ; HLA Antigens/immunology/genetics ; Vaccination ; Renal Dialysis ; Antibodies, Viral/blood/immunology ; Spike Glycoprotein, Coronavirus/immunology/genetics ; BNT162 Vaccine/immunology ; Vulnerable Populations ; Adult ; T-Lymphocytes/immunology ; }, abstract = {HLA genes exhibit a high degree of polymorphism, contributing to genetic variability known to influence immune responses to infection. Here we investigate associations between HLA polymorphism and serological and T-lymphocyte responses to the BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines within a population receiving maintenance haemodialysis (HD) for End-Stage Renal Disease (ESRD). Our primary objective was to identify HLA alleles associated with diminished serological and T-cellular responsiveness to vaccination. As a secondary objective, the associations between HLA type and COVID-19 disease outcomes were investigated using an independent ESRD cohort (n = 327). This aimed to determine if the alleles associated with poor vaccine response were also linked to unfavourable infection outcomes. In the main study, serum from 225 SARS-CoV-2 infection-naïve patients was HLA-typed using high-resolution Next Generation Sequencing, and serological titres were analysed for the presence of SARS-CoV-2 spike glycoprotein-specific antibodies after two doses of vaccination. A subset of patients (n = 33) was also tested for a T-lymphocyte response. Overall, 89% (n = 200) of patients seroconverted, but only 18% (n = 6) of the cellular response subgroup had a positive T-lymphocyte response. The HLA class II alleles DPB1*104:01, DRB1*04:03 and DRB1*14:04 and HLA class I alleles B*08:01 and B*18:01 were found to significantly correlate with seronegativity, and DQB1*06:01 correlated with serological responsiveness. We were unable to analyse the effect of HLA on disease outcome and T-lymphocyte response due to sample size limitations. Our results suggest pathways for further research and begin to elucidate the relationship between HLA polymorphism and immune responses in the vulnerable ESRD population.}, } @article {pmid39993446, year = {2025}, author = {Kouyoumdjian, JA and Yamamoto, LAR and Graca, CR}, title = {Jitter and muscle fiber conduction velocity in long COVID fatigue.}, journal = {Arquivos de neuro-psiquiatria}, volume = {83}, number = {1}, pages = {1-8}, doi = {10.1055/s-0045-1802961}, pmid = {39993446}, issn = {1678-4227}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; *Electromyography ; Middle Aged ; *Muscle Fibers, Skeletal/physiology ; Adult ; Case-Control Studies ; *Neural Conduction/physiology ; *Post-Acute COVID-19 Syndrome ; Aged ; Neuromuscular Junction/physiopathology ; Muscle Fatigue/physiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long coronavirus disease (long COVID, LC) is defined as the continuation or development of new symptoms 3 months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In LC, the rate of fatigue/postexertional malaise (F-PEM) has been described to be as high as 70%, regardless of age or severity of the acute symptoms.

OBJECTIVE:  To evaluate the neuromuscular junction (NMJ) function and the isolated muscle fiber conduction velocity (MFCV) in situ in LC cases and controls.

METHODS:  We studied 37 subjects without SARS-CoV-2 (controls) and 32 cases of SARS-CoV-2 infection, half with LC symptoms (LC-yes) and half without them (LC-no). Single-fiber electromyography (jitter measured with a concentric electrode), MFCV, the fast-to-slow MFCV ratio (F/S ratio), and the motor unit potentials (MUPs) were taken in the tibialis anterior muscle.

RESULTS:  At least 1 jitter parameter was abnormal in 1/37 controls, in 1/16 LC-no patients, and in 2/16 LC-yes patients, without significant differences among them. None of the subjects with abnormal jitter presented fluctuation symptoms or positive acetylcholine-receptor antibody. The MFCV and F/S ratios did not show abnormalities in any of the participants. The MUPs did not show myopathic or neurogenic abnormality in needle electromyography. The most frequent symptom in LC was F-PEM, which occurred in all LC-yes patients and was significantly different from the other groups.

CONCLUSION:  Fatigue/postexertional malaise was found in all cases of LC, and the electrophysiological findings did not indicate the muscle fiber or the NMJ as a relevant factor in this condition.}, } @article {pmid39990570, year = {2025}, author = {Jayavelu, ND and Samaha, H and Wimalasena, ST and Hoch, A and Gygi, JP and Gabernet, G and Ozonoff, A and Liu, S and Milliren, CE and Levy, O and Baden, LR and Melamed, E and Ehrlich, LIR and McComsey, GA and Sekaly, RP and Cairns, CB and Haddad, EK and Schaenman, J and Shaw, AC and Hafler, DA and Montgomery, RR and Corry, DB and Kheradmand, F and Atkinson, MA and Brakenridge, SC and Higuita, NIA and Metcalf, JP and Hough, CL and Messer, WB and Pulendran, B and Nadeau, KC and Davis, MM and Geng, LN and Sesma, AF and Simon, V and Krammer, F and Kraft, M and Bime, C and Calfee, CS and Erle, DJ and Langelier, CR and , and Guan, L and Maecker, HT and Peters, B and Kleinstein, SH and Reed, EF and Diray-Arce, J and Rouphael, N and Altman, MC}, title = {Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.12.25322164}, pmid = {39990570}, abstract = {The post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID, remain a significant health issue that is incompletely understood. Predicting which acutely infected individuals will go on to develop long COVID is challenging due to the lack of established biomarkers, clear disease mechanisms, or well-defined sub-phenotypes. Machine learning (ML) models offer the potential to address this by leveraging clinical data to enhance diagnostic precision. We utilized clinical data, including antibody titers and viral load measurements collected at the time of hospital admission, to predict the likelihood of acute COVID-19 progressing to long COVID. Our machine learning models achieved median AUROC values ranging from 0.64 to 0.66 and AUPRC values between 0.51 and 0.54, demonstrating their predictive capabilities. Feature importance analysis revealed that low antibody titers and high viral loads at hospital admission were the strongest predictors of long COVID outcomes. Comorbidities, including chronic respiratory, cardiac, and neurologic diseases, as well as female sex, were also identified as significant risk factors for long COVID. Our findings suggest that ML models have the potential to identify patients at risk for developing long COVID based on baseline clinical characteristics. These models can help guide early interventions, improving patient outcomes and mitigating the long-term public health impacts of SARS-CoV-2.}, } @article {pmid39990549, year = {2025}, author = {Li, H and Yang, Y and Ding, P and Xu, R}, title = {Causal association of long COVID with brain structure changes: Findings from a 2-sample Mendelian randomization study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.12.25322170}, pmid = {39990549}, abstract = {Nearly 7.5% U.S. adults have long COVID. Recent epidemiological studies indicated that long COVID, is significantly associated with subsequent brain structure changes. However, it remains unknown if long COVID is causally associated with brain structure change. Here we applied two Mendelian Randomization (MR) methods - Inverse Variance Weighting MR method (IVW) for correlated instrument variables and Component analysis-based Generalized Method of Moments (PC-GMM) - to examine the potential causal relationships from long COVID to brain structure changes. The MR study was based on an instrumental variable analysis of data from a recent long COVID genome-wide association study (GWAS) (3,018 cases and 994,582 controls), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) (Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). We found no significant causal relationship between long COVID and brain structure changes. As we gain more insights into long COVID and its long-term health outcomes, future works are necessary to validate our findings and understand the mechanisms underlying the observed associations, though not causal, of long COVID with subsequent brain structure changes.}, } @article {pmid39990545, year = {2025}, author = {Song, Y and Mehl, F and Muehling, LM and Canderan, G and Enfield, K and Sun, J and Yin, MT and Ratcliffe, SJ and Wilson, JM and Kadl, A and Woodfolk, J and Zeichner, SL}, title = {ACE-2-like Enzymatic Activity in COVID-19 Convalescent Patients with Persistent Pulmonary Symptoms Associated with Immunoglobulin.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.12.25322167}, pmid = {39990545}, abstract = {Many difficult to understand clinical features characterize COVID-19 and Post-Acute Sequelae of COVID-19 (PASC or Long COVID, LC). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein Receptor Binding Domain (RBD) binds Angiotensin Converting Enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some patients may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some acute COVID-19 patients had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some COVID-19 patients indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 patients or whether ACE2-like abzymes could also be identified in convalescent COVID-19 patients. Here we show that some convalescent COVID-19 patients attending a clinic for patients with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test.}, } @article {pmid39990442, year = {2025}, author = {Gabernet, G and Maciuch, J and Gygi, JP and Moore, JF and Hoch, A and Syphurs, C and Chu, T and Jayavelu, ND and Corry, DB and Kheradmand, F and Baden, LR and Sekaly, RP and McComsey, GA and Haddad, EK and Cairns, CB and Rouphael, N and Fernandez-Sesma, A and Simon, V and Metcalf, JP and Agudelo Higuita, NI and Hough, CL and Messer, WB and Davis, MM and Nadeau, KC and Pulendran, B and Kraft, M and Bime, C and Reed, EF and Schaenman, J and Erle, DJ and Calfee, CS and Atkinson, MA and Brackenridge, SC and Melamed, E and Shaw, AC and Hafler, DA and Ozonoff, A and Bosinger, SE and Eckalbar, W and Maecker, HT and Kim-Schulze, S and Steen, H and Krammer, F and Westendorf, K and Network, I and Peters, B and Fourati, S and Altman, MC and Levy, O and Smolen, KK and Montgomery, RR and Diray-Arce, J and Kleinstein, SH and Guan, L and Ehrlich, LIR}, title = {Identification of a multi-omics factor predictive of long COVID in the IMPACC study.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.12.637926}, pmid = {39990442}, issn = {2692-8205}, abstract = {Following SARS-CoV-2 infection, ∼10-35% of COVID-19 patients experience long COVID (LC), in which often debilitating symptoms persist for at least three months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities. We utilized machine learning methods on biologic analytes and patient reported outcome surveys provided over 12 months after hospital discharge from >500 hospitalized COVID-19 patients in the IMPACC cohort to identify a multi-omics "recovery factor". IMPACC participants who experienced LC had lower recovery factor scores compared to participants without LC. Biologic characterization revealed increased levels of plasma proteins associated with inflammation, elevated transcriptional signatures of heme metabolism, and decreased androgenic steroids in LC patients. The recovery factor was also associated with altered circulating immune cell frequencies. Notably, recovery factor scores were predictive of LC occurrence in patients as early as hospital admission, irrespective of acute disease severity. Thus, the recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.}, } @article {pmid39990283, year = {2025}, author = {Ramli, Y and Prawiroharjo, P and Wiratman, W and Tenda, E and Ibrahim, N and Susilaradeya, D and Reza, A and Agatha, J and Siagian, R and Fauhan, H and Evelyn, F and Ugawa, Y and Yusuf, P}, title = {The relationship between cognitive function and neuropsychiatric disorders with quantitative electroencephalogram (qEEG) on long COVID syndrome patients.}, journal = {Brain, behavior, & immunity - health}, volume = {44}, number = {}, pages = {100954}, pmid = {39990283}, issn = {2666-3546}, abstract = {BACKGROUND: The COVID-19 pandemic has resulted in long-term consequences for a subset of affected individuals, known as long COVID syndrome. The neurological and psychiatric effects of this condition remain incompletely understood. This study aims to evaluate heightened common mental disorders in long COVID through assessing psychiatric, cognitive, neurophysiological aspects, and emphasizing lasting mental health impacts.

METHODS: This cross-sectional study compared patients with long COVID to those who had recovered from COVID-19 without residual symptoms using quantitative electroencephalogram (qEEG) analysis. We conducted qEEG analyses, and Montreal Cognitive Assessment (MoCA) and Self-Rating Questionnaire (SRQ) tests on participants. Analyses included brain spectrum examination, hemispheric asymmetry, and inter-electrode connectivity.

RESULTS: Analyses revealed lower MoCA scores in the memory domain were lower in the long COVID group (Mann Whitney Utest), indicating that individuals with long COVID experience more substantial cognitive deficits. There is no statistical difference for spectrum examination and hemispheric asymmetry observed in the qEEG data between the COVID and long COVID groups. Connectivity analysis showed statistically significant higher connectivity in temporal-occipital (T6-O2) in long COVID groups (Mann Whitney Utest).

CONCLUSION: Our findings underscore the persistent neuropsychiatric impact of COVID-19, particularly in long COVID patients. Notably, working memory deficits in MoCA scores were identified as one of the most frequent neuropsychological symptoms in these individuals. Decreased brain connectivity indicates cognitive-sensorimotor decline and is confirmed by the frequent brain fog symptoms in long COVID.}, } @article {pmid39990183, year = {2025}, author = {Łukomska, E and Kloc, K and Kowalska, M and Matjaszek, A and Joshi, K and Scholz, S and Van de Velde, N and Beck, E}, title = {Healthcare Resource Utilization (HCRU) and Direct Medical Costs Associated with Long COVID or Post-COVID-19 Conditions: Findings from a Literature Review.}, journal = {Journal of market access & health policy}, volume = {13}, number = {1}, pages = {7}, pmid = {39990183}, issn = {2001-6689}, abstract = {Approximately 10-20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6-13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4-10% increase in long-term total HCRU over 6-8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.}, } @article {pmid39987891, year = {2025}, author = {Rees, K and Aicheler, R and Butcher, L and Dodd, A and Geen, J and Lynch, C and Massey, I and Morris, K and Tennant, B and Webb, R}, title = {Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.}, journal = {Cytokine}, volume = {189}, number = {}, pages = {156884}, doi = {10.1016/j.cyto.2025.156884}, pmid = {39987891}, issn = {1096-0023}, abstract = {This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to long-COVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally). DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated. Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting 'summer' sub-cohort (but not the 'winter' sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes. While interpretation is complicated by seasonal variations, these findings may be of medical/biomedical value. Importantly, as IL-6 was higher in long-COVID sufferers than healthy controls, and rs2228145 AA genotype-bearing individuals within our 'summer' sub-cohort were at elevated risk of developing long-COVID, these findings point towards possible future use of IL-6 and/or rs2228145 genotype as biomarkers predictive of long-COVID risk, which may bring advantages regarding management and treatment of long-COVID.}, } @article {pmid39984803, year = {2025}, author = {Ivlev, I and Wagner, J and Phillips, T and Treadwell, JR}, title = {Interventions for Long COVID: A Narrative Review.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {39984803}, issn = {1525-1497}, support = {MSA-SOW#05-ECRI-ENG-11-07-2022/PCORI/Patient-Centered Outcomes Research Institute/United States ; }, abstract = {Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.}, } @article {pmid39983460, year = {2025}, author = {Nayyerabadi, M and Fourcade, L and Joshi, SA and Chandrasekaran, P and Chakravarti, A and Massé, C and Paul, ML and Houle, J and Boubekeur, AM and DuSablon, C and Boudreau, V and Bovan, D and Darbinian, E and Coleman, EA and Vinci, S and Routy, JP and Hétu, PO and Poudrier, J and Falcone, EL}, title = {Corrigendum to "Vaccination after developing long COVID: Impact on clinical presentation, viral persistence and immune responses" [International Journal of Infectious Diseases, volume 136 (2023), 136-145, doi:10.1016/j.ijid.2023.09.006].}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {153}, number = {}, pages = {107842}, doi = {10.1016/j.ijid.2025.107842}, pmid = {39983460}, issn = {1878-3511}, } @article {pmid39983332, year = {2025}, author = {Ilari, S and Nucera, S and Passacatini, LC and Caminiti, R and Mazza, V and Macrì, R and Serra, M and Scarano, F and Malafoglia, V and Palma, E and Oppedisano, F and Maiuolo, J and Tomino, C and Mollace, V and Muscoli, C}, title = {SIRT1: A likely key for future therapeutic strategies for pain management.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107670}, doi = {10.1016/j.phrs.2025.107670}, pmid = {39983332}, issn = {1096-1186}, abstract = {Sirtuin 1 (SIRT1), a NAD+ -dependent histone deacetylase, plays a crucial role in mitigating oxidative stress, regulating inflammation, and maintaining mitochondrial function. Reduced SIRT1 activity has been linked to elevated pro-inflammatory cytokines, mitochondrial dysfunction, and chronic pain, all of which are observed in long COVID pathology. Emerging evidence identifies mitochondrial dysfunction and oxidative stress as central contributors to these symptoms. Increases reactive oxygen species (ROS) such as superoxide, nitric oxide, and peroxynitrite, leading to oxidative damage, chronic inflammation, and central/peripheral sensitization. Nutraceuticals, particularly the polyphenolic fraction of bergamot (BPF), have demonstrated potent antioxidant, anti-inflammatory, and antiviral properties. This study highlights BPF's ability to modulate SIRT1 activity in a rat model of inflammation and hyperalgesia. It provides novel evidence of SIRT1 nitration within the nucleus as a key event in inflammatory pain pathogenesis. BPF administration preserved SIRT1 activity, reduced oxidative stress markers such as malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG), and minimized post-translational modifications of nuclear proteins, including nitration, acetylation, and carbonylation. Additionally, it alleviated hyperalgesia and allodynia. These findings underscore the therapeutic potential of polyphenols like BPF in reducing oxidative stress and inflammation-driven pain. By activating SIRT1, BPF may provide relief for pain conditions. Further research on SIRT1-targeted therapies is essential to combat inflammation and oxidative stress, preventing chronic conditions and enhancing treatment options.}, } @article {pmid39982603, year = {2025}, author = {Szabo, S and Muzyka, I and Muller, V and Szabo, AJ and Szijártó, A and Gyires, K and Doczi, T and Janszky, J and Stengel, A and Göpel, S and Trichopoulou, A and Diaz, R and Camacho, N and Malatinszky, G and Lambrecht, N and Zayachkivska, O}, title = {Long COVID has variable incidence and clinical presentations: our 6-country collaborative study.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {39982603}, issn = {1568-5608}, abstract = {Following the acute COVID-19 disease, many countries see long-time sequences of this infectious disease, commonly known as Long COVID. This seems to be a multi-organ inflammatory chronic condition of variable intensity and incidence, partly due to the retention of the virus or viral particles in several organs. Based on our 6-country (4 in Europe, 2 from North America) collaborative investigations, we found that the incidence of Long COVID varied from 46 (Mexico) to 17% (Ukraine), the average being 25%. In a summary evaluation of all 6 countries, we characterized as "general" the most frequent presenting signs and symptoms: fatigue (47%), hair loss (39.2%), and myalgia (35%), but no two countries demonstrated the same top 3 clinical signs/symptoms. Hence, we promote the following 3 key points: 1. to expand international collaborations to better understand not only the prevalence and incidence of Long COVID but also to gain insights into the pathogenesis, and identify predisposing factors and diagnostic biomarkers of Long COVID; 2. find or develop new drugs for the treatments of Long COVID and identify appropriate rehabilitation, potentially organ-specific strategies; 3. most importantly, to start long-term observational studies (e.g., for 5-10-15 years) to identify potential increased cancer incidence in any organ, especially, since we know that certain viruses are carcinogens.}, } @article {pmid39982452, year = {2025}, author = {Theobald, D and de Castro Braz, LE and Akula, SM and Eells, JB and Sriramula, S}, title = {Inhibition of kinin B1 receptor alleviates SARS-CoV-2 induced long-lasting cardiovascular complications.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpheart.00861.2024}, pmid = {39982452}, issn = {1522-1539}, support = {5R01HL153115//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL152297//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; //Federal COVID-19 Relief Funds to Brody School of Medicine/ ; }, abstract = {Long COVID has been associated with significant cardiovascular complications, including fibrosis, functional impairment, and chronic inflammatory and immune responses. However, the underlying mechanisms driving these cardiac pathologies following COVID-19 infection remain understudied. Previously, we characterized a mouse model of long COVID and observed enhanced expression of kinin B1 receptor (B1R) in the infected animals. Here, we investigated the role of B1R in mediating long COVID induced cardiac pathologies. K18-hACE2 transgenic mice were infected intranasally with SARS-CoV-2 and evaluated at 28 days post-infection (dpi) to model long COVID and the effects of pharmacological blockade of B1R were evaluated. Persistent upregulation of B1R expression was accompanied by apoptosis, disrupted cardiomyocyte architecture, fibrosis, impaired gap junction integrity, and sustained inflammation and immune cell infiltration. B1R blockade restored gap junction integrity, reduced fibrosis and apoptosis, and mitigated inflammation and immune activation. Together, these data indicate that B1R plays a critical role in long COVID induced cardiac remodeling and damage, highlighting its potential as a target for treating long-lasting cardiovascular complications following SARS-CoV-2 infection.}, } @article {pmid39981885, year = {2025}, author = {Zhang, Y and Chen, H and Li, Y and Luo, C and Zhu, Y and Zhou, X and Wang, R and He, J and Guo, H and Xu, X and Qiu, M and Li, J}, title = {Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.}, journal = {Journal of medical virology}, volume = {97}, number = {2}, pages = {e70237}, doi = {10.1002/jmv.70237}, pmid = {39981885}, issn = {1096-9071}, mesh = {Animals ; *Disease Models, Animal ; *COVID-19/epidemiology ; Humans ; Mice ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Primates ; Cricetinae ; Mesocricetus ; }, abstract = {Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses a significant ongoing threat to public health. Foundational scientific studies are needed to unravel the underlying mechanisms, with the ultimate goal of developing effective preventative and therapeutic strategies. Therefore, there is an urgent demand for animal models that can accurately replicate the clinical features of LC. This review integrates clinical epidemiological data to summarize the pathological changes in extrapulmonary systems involved in LC. Additionally, it critically examines the capacity of existing animal models, including nonhuman primates, genetically modified mice, and Syrian hamsters, to exhibit enduring postinfection symptoms that align with human clinical manifestations, and identifies key areas requiring further development. The objective is to offer insights that will aid in the development of next-generation animal models, thereby accelerating our understanding of how acute respiratory viral infections transition into chronic conditions, and ensuring preparedness for future pandemics.}, } @article {pmid39980359, year = {2025}, author = {Bistagnino, F and Subramanian, A and Tovani-Palone, MR}, title = {Navigating the (Post-) Pandemic Landscape: An Analysis of COVID-19's Current Status and Future Implications.}, journal = {Disaster medicine and public health preparedness}, volume = {19}, number = {}, pages = {e44}, doi = {10.1017/dmp.2025.10}, pmid = {39980359}, issn = {1938-744X}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Pandemics ; Public Health/methods/trends ; SARS-CoV-2 ; }, abstract = {Although it is true that the coronavirus disease 2019 (COVID-19) situation has improved significantly around the world, especially after the implementation of mass vaccination campaigns, there is still a lack of consensus both in the literature and among health authorities and other stakeholders about the current epidemiological situation. This, in turn, has been intensified after the World Health Organization declared the end of the public health emergency of international concern related to COVID-19. In this context, worrying questions have arisen, including a rampant dissemination of scientific misinformation coupled with increased resistance to the implementation and/or revocation of appropriate public health measures. In response to these challenges and hoping to contribute to their mitigation, this article addresses current aspects about the epidemiological situation of COVID-19, discusses long COVID and its controversies, the intensification of scientific misinformation as well as considerations on related health surveillance, and recommendations for improving the existing situation.}, } @article {pmid39979349, year = {2025}, author = {Kato, H and Ichihara, N and Saito, H and Fujitani, S and Ota, K and Takahashi, Y and Harada, T and Hattori, T and Komeya, M and Hosozawa, M and Muto, Y and Hori, M and Iba, A and Iso, H and Iso, H and , }, title = {Prevalence of erectile dysfunction as long-COVID symptom in hospitalized Japanese patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6279}, pmid = {39979349}, issn = {2045-2322}, support = {JPMH21HA2011//MHLW Research on Emerging and Re-emerging Infectious Diseases and Immunization/ ; }, mesh = {Humans ; Male ; *Erectile Dysfunction/epidemiology ; *COVID-19/epidemiology/complications/psychology ; Middle Aged ; Japan/epidemiology ; Prevalence ; Adult ; Case-Control Studies ; SARS-CoV-2/isolation & purification ; Aged ; Surveys and Questionnaires ; Hospitalization ; Depression/epidemiology ; Anxiety/epidemiology ; East Asian People ; }, abstract = {Coronavirus disease-2019 (COVID-19) is associated with a wide range of post-acute sequelae. The prevalence of erectile dysfunction (ED) that developed after COVID-19 and the associated underlying factors were analyzed based on a questionnaire survey, COVID-19 Recovery Study II in Japan. A case-control study was conducted with those with or without ED one and two years hospitalized with COVID-19 between March and September 2021. Six hundred and nine Japanese men, with a median age of 48 years, were analyzed. During the study period, 116 subjects (19.0%) had erectile dysfunction. The patients with ED responded with less subjective awareness of recovery and high breathless and fatigue scores compared to those without ED. The patients with ED also showed higher Hospital Anxiety and Depression Scale-D (depression) and the EuroQol 5-dimensions 5-level scores for pain/discomfort and anxiety/depression scores compared before COVID-19 infection. Sleep disturbance was suggested to be associated with erectile dysfunction using an exploratory clustering analysis in the one-year survey. There were no associations of COVID-19 severity, reinfection, vaccination frequency, antiviral treatment for COVID-19 with the presence of erectile dysfunction. It was considered that mental support for the subject with erectile dysfunction as a long-COVID symptom is warranted.}, } @article {pmid39978124, year = {2025}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Patients' experiences of long-covid neuropsychological symptoms: Comment.}, journal = {Atencion primaria}, volume = {57}, number = {8}, pages = {103241}, doi = {10.1016/j.aprim.2025.103241}, pmid = {39978124}, issn = {1578-1275}, } @article {pmid39977893, year = {2024}, author = {Salih, R and Hassan, R and Ibrahim, SN and Omer, H and Abdelsamad, A and Elmustafa, F and Elomeiri, L and Mahmoud, S and Ahmed, M and Alsamani, RH and Abdalla, R and Abdelrahman, N}, title = {The Neuro-cognitive Implications of COVID-19 Infection: A Systematic Review with an Insight into the Pathophysiology (P11-13.009).}, journal = {Neurology}, volume = {102}, number = {7_supplement_1}, pages = {6303}, doi = {10.1212/WNL.0000000000206382}, pmid = {39977893}, issn = {1526-632X}, mesh = {Humans ; *COVID-19/complications/psychology/physiopathology ; Cognitive Dysfunction/physiopathology/etiology ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: This study aimed to investigate the evidence of neuro-cognitive symptoms observed in COVID-19 patients and explore the underlying mechanisms.

BACKGROUND: The COVID-19 pandemic has been affecting millions globally. Besides other presentation of long covid, evidence shows persistent cognitive impact, imposing further clinical and psychosocial challenges.

DESIGN/METHODS: a systematic review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search in electronic databases using google scholar and pubmed from 2020 to 2023 was conducted.

RESULTS: Out of the initial 435 studies, 111 studies investigating the neurocognitive impact of COVID-19 and its pathophysiology were examined. Several neuro-cognitive symptoms were reported; namely, executive dysfunction, memory loss, attention deficit, fatigue, anxiety, delirium, and processing speed delay. Other symptoms were also identified. The exact pathophysiological mechanism behind the cognitive effects is not clear. However, the review collected evidence that suggests several potential mechanisms. The virus may enter the central nervous system (CNS) through the olfactory nerve, vascular endothelial cells, or immune cells, breaking the blood-brain barrier by binding to the ACE2 receptor. Once in the brain, the virus can cause direct and indirect damage through various mechanisms The review yielded that the combination of direct replication, immune-related inflammation involving cytokines as IL-6, TNFα, and IL-1β, immune dysregulation, vascular changes, low oxygen, brain hypometabolism, neurotransmitter imbalances, oxidative stress and amyloid deposit are responsible of the neurocognitive implications. Interestingly, many studies showed that the cognitive impacts correlate with disease severity and psychiatric manifestations. Also, the studies emphasized the role of neuroimaging including 18F FDG PET scans (Positron Emission Tomography scans), in understanding the cognitive effects of COVID-19.

CONCLUSIONS: Neuro-cognitive sequelae of covid-19 are well documented. Although several hypotheses on the mechanism have been published, more data is needed for the extended impact of COVID-19 including the use of validated cognitive tests before and after the infections. Disclosure: Ms. Salih has nothing to disclose. Dr. Hassan has nothing to disclose. Dr. Ibrahim has nothing to disclose. Dr. Omer has nothing to disclose. Dr. Abdelsamad has nothing to disclose. Dr. Elmustafa has nothing to disclose. Dr. Elomeiri has nothing to disclose. Dr. Mahmoud has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Hassan Alsamani has nothing to disclose. Dr. Abdalla has nothing to disclose. Dr. Abdelrahman has nothing to disclose.}, } @article {pmid39974559, year = {2025}, author = {Ewing, AG and Salamon, S and Pretorius, E and Joffe, D and Fox, G and Bilodeau, S and Bar-Yam, Y}, title = {Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.}, journal = {Medical review (2021)}, volume = {5}, number = {1}, pages = {66-75}, pmid = {39974559}, issn = {2749-9642}, abstract = {Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.}, } @article {pmid39973734, year = {2025}, author = {Jaber, F and Hoang, MA and Feldman, DE and Saunders, S and Mazer, B}, title = {Factors associated with changes in employment in individuals with long COVID.}, journal = {Work (Reading, Mass.)}, volume = {}, number = {}, pages = {10519815241300409}, doi = {10.1177/10519815241300409}, pmid = {39973734}, issn = {1875-9270}, abstract = {BACKGROUND: Long Covid symptoms are known to have an impact on function, however, their effect on employment and the associated demographic and clinical factors are not well understood.

OBJECTIVE: Our objectives were (1) To compare changes in employment status between those with Long Covid and those who recovered from their Covid-19 infection; and (2) To identify demographic factors, clinical factors, and occupational skill level associated with decreased employment status in those with Long Covid.

METHODS: We conducted an electronic survey (≥12 weeks post infection) with adult residents in Laval, Quebec, Canada who tested positive for Covid-19 between March 2020 and January 2022, regarding Long Covid symptoms and their functional impact. This analysis focuses on employment status: pre-covid, prior to infection, and current, and was recorded as full-time, part-time, or not working due to illness or for other reasons. Change in employment status was categorized as no decrease or decreased.

RESULTS: Among 2764 respondents, 15.6% (95% CI: 13.3-17.9) with Long Covid (versus 5.4% (95% CI: 4.2-6.5) who recovered) experienced a decrease in employment (p < 0.001). Clinical factors associated with a decrease in employment include having been hospitalized for Covid-19, having ≥1 comorbid condition prior to infection, >12 months since infection, moderate to severe decline in physical and psychological health, and decline in global health. Demographic factors and occupational skill level were not associated with a change in employment.

CONCLUSIONS: Persons with Long Covid are more likely to experience a decrease in employment. Research is needed to determine whether rehabilitation for people with Long Covid could improve employment levels.}, } @article {pmid39973713, year = {2025}, author = {Aribou, ZM and Tan, AKW and Lim, SM and Lim, JW and Gan, WH and Ng, WT and Koh, DSQ}, title = {Assessing the impact of Long COVID on healthcare workers' work - role functioning in tertiary hospitals in Singapore.}, journal = {Work (Reading, Mass.)}, volume = {}, number = {}, pages = {10519815251319233}, doi = {10.1177/10519815251319233}, pmid = {39973713}, issn = {1875-9270}, abstract = {BACKGROUND: Understanding Long COVID's impact on healthcare workers (HCWs) is vital for patient safety and care quality. However, research on its prevalence among HCWs in Singapore and its work impact is lacking.

OBJECTIVE: This study aims to assess Long COVID prevalence and its impact on work role functioning among HCWs in two Singapore tertiary hospitals, filling a critical gap in the literature.

METHODS: Conducted from January to April 2023, this study evaluated Long COVID prevalence and its impact on HCWs' work-role functioning in two Singapore tertiary hospitals. HCWs over 21, having experienced ≥1 COVID-19 infection, participated in an online survey. Long COVID, defined by NICE criteria, entailed symptoms persisting for 4 or more weeks. Work-related functioning was assessed using WRFQv2.0. Descriptive analyses were conducted using STATA software.

RESULTS: Out of 15,882 eligible participants, 573 responded (3.6% response rate). Long COVID prevalence (symptoms persisting for ≥4 weeks) was 47.5%, notably higher among younger HCWs (<40 years old), those with moderate/severe infections, and multiple infections. HCWs with Long COVID had significantly lower WRFQv2.0 mean scores compared to those without (85.1 vs. 74.3, p < 0.05). Additionally, HCWs with symptoms for ≥12 weeks had significantly lower scores than those without Long COVID (85.6 vs. 74.3, p < 0.05).

CONCLUSION: This study underscores Long COVID's potential impact on HCWs' work role functioning, especially among those with prolonged symptoms. Tailored work adjustments are crucial for their successful return to pre-illness levels, highlighting the importance of addressing Long COVID in healthcare settings.}, } @article {pmid39972044, year = {2025}, author = {Lu, JY and Lu, JY and Wang, S and Duong, KS and Henry, S and Fisher, MC and Duong, TQ}, title = {Long term outcomes of patients with chronic kidney disease after COVID-19 in an urban population in the Bronx.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6119}, pmid = {39972044}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Renal Insufficiency, Chronic/epidemiology/complications ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; *Disease Progression ; Hospitalization ; Urban Population ; SARS-CoV-2/isolation & purification ; Cardiovascular Diseases/epidemiology/etiology ; Risk Factors ; New York City/epidemiology ; }, abstract = {We investigated the long-term kidney and cardiovascular outcomes of patients with chronic kidney disease (CKD) after COVID-19. Our retrospective cohort consisted of 834 CKD patients with COVID-19 and 6,167 CKD patients without COVID-19 between 3/11/2020 to 7/1/2023. Multivariate competing risk regression models were used to estimate risk (as adjusted hazard ratios (aHR) with 95% confidence intervals (CI)) of CKD progression to a more advanced stage (Stage 4 or 5) and major adverse kidney events (MAKE), and risk of major adverse cardiovascular events (MACE) at 6-, 12-, and 24-month follow up. Hospitalized COVID-19 patients at 12 and 24 months (aHR 1.62 95% CI[1.24,2.13] and 1.76 [1.30, 2.40], respectively), but not non-hospitalized COVID-19 patients, were at higher risk of CKD progression compared to those without COVID-19. Both hospitalized and non-hospitalized COVID-19 patients were at higher risk of MAKE at 6-, 12- and 24-months compared to those without COVID-19. Hospitalized COVID-19 patients at 6-, 12- and 24-months (aHR 1.73 [1.21, 2.50], 1.77 [1.34, 2.33], and 1.31 [1.05, 1.64], respectively), but not non-hospitalized COVID-19 patients, were at higher risk of MACE compared to those without COVID-19. COVID-19 increases the risk of long-term CKD progression and cardiovascular events in patients with CKD. These findings highlight the need for close follow up care and therapies that slow CKD progression in this high-risk subgroup.}, } @article {pmid39971694, year = {2025}, author = {Tsang, MS and Zhou, IW and Zhang, AL and Xue, CC}, title = {Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials.}, journal = {Journal of integrative medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.joim.2025.01.001}, pmid = {39971694}, issn = {2095-4964}, abstract = {BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted.

OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT).

SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023.

INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment.

DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I[2].

RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I[2] = 68%) and low certainty.

CONCLUSION: CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: a systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; Epub ahead of print.}, } @article {pmid39969545, year = {2025}, author = {Pfoser-Poschacher, V and Keilani, M and Steiner, M and Schmeckenbecher, J and Zwick, RH and Crevenna, R}, title = {Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue.}, journal = {Wiener klinische Wochenschrift}, volume = {}, number = {}, pages = {}, pmid = {39969545}, issn = {1613-7671}, abstract = {BACKGROUND: The COVID-19 pandemic has led to significant health challenges, with some individuals developing long COVID characterized by persistent symptoms such as fatigue, dyspnea and cognitive difficulties lasting weeks or months after infection. This condition predominantly affects women and may involve prolonged inflammation and autonomic nervous system dysfunction. Current treatments focus on symptom relief and vagus nerve stimulation (VNS) is being investigated for its potential therapeutic benefits.

METHODS: This pilot study was a prospective, blinded, randomized controlled trial involving 36 female long COVID patients aged 18-70 years. Participants were assigned to three groups receiving VNS at frequencies of 10 Hz, 25 Hz, or a control of 2 Hz for 3 months. Outcomes were assessed at baseline, after 4 and 12 weeks.

RESULTS: The study revealed that all VNS treatment groups experienced reduction in symptoms associated with long COVID, particularly in fatigue and dyspnea, after 12 weeks. Participants across all frequencies reported an improvement in health-related quality of life. Heart rate variability remained stable throughout the trial, and no significant changes in morning salivary cortisol levels were seen across groups.

DISCUSSION: Vagus nerve stimulation may offer therapeutic benefits for women with long COVID, particularly in reducing fatigue and dyspnea. The treatment was found to be safe, with no significant side effects reported; however, further research with larger study groups is needed to confirm these findings and examine the long-term effects of VNS on autonomic nervous system function.}, } @article {pmid39969268, year = {2024}, author = {Solopov, PA and Colunga Biancatelli, RML and Day, T and Gregory, B and Sharlow, ER and Lazo, JS and Catravas, JD}, title = {KVX-053, a protein tyrosine phosphatase 4A3 inhibitor, ameliorates SARS-CoV-2 spike protein subunit 1-induced acute lung injury in mice.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {392}, number = {3}, pages = {100022}, doi = {10.1124/jpet.124.002154}, pmid = {39969268}, issn = {1521-0103}, abstract = {Acute respiratory distress syndrome (ARDS), often preceded by acute lung injury (ALI), is characterized by the accumulation of inflammatory fluid in the lung alveoli, leaky alveolar epithelium and endothelium, and overexpression of proinflammatory cytokines. This progression from ALI to ARDS is a major contributor to the high mortality observed in patients with COVID-19. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to lung angiotensin-converting enzyme 2 (ACE2), and in addition to facilitating viral cell entry, it plays an important role in the development of ALI and ARDS, especially in the later phases of COVID-19 as well as long-COVID. Protein tyrosine phosphatase (PTP) 4A3 is a key mediator of ARDS pathology. This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19-associated ALI. Intratracheal administration of SARS-CoV-2 spike protein subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines, structural lung injury, and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings provide the first evidence supporting a role for PTP4A3 in the development of SARS-CoV-2-mediated ALI. SIGNIFICANCE STATEMENT: This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19-associated ALI/ARDS. Intratracheal administration of SARS-CoV-2 spike protein subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines and chemokines, structural lung injury, and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings suggest that this novel PTP4A3 inhibitor may be useful against COVID-19 and potentially other viral-induced ARDS.}, } @article {pmid39968869, year = {2025}, author = {Olsson-Åkefeldt, S and Luthander, J and Anmyr, L and Villard, L and Arnason, S and Kemani, MK and Wållgren, E and Röstlund, S and Tingborn, M and Pettersson, M and George, E and Ryd-Rinder, M and Hertting, O}, title = {Poor Association Between Clinical Characteristics and Seropositivity in Children With Suspected Long COVID-A Single-Centre Study.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.70034}, pmid = {39968869}, issn = {1651-2227}, support = {//Henry and Ella Margareta Stahl Foundation/ ; //The Pediatric Research Foundation at Astrid Lindgren Children's Hospital/ ; }, abstract = {AIM: We aimed to compare characteristics and clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody positive or negative children attending a specialist outpatient clinic for suspected paediatric long COVID.

METHODS: A cross-sectional study was conducted of 113 children and adolescents enrolled between 1 December 2020 to 14 September 2021 in a multidisciplinary programme. Clinical and epidemiological data were collected with standardised interviews and laboratory tests including SARS-CoV-2 spike antibody measurement.

RESULTS: A serological link to SARS-CoV-2 infection was found in 52%. Most patients (94.7%) reported several symptoms. Fatigue, post-exertional malaise, dizziness, nausea, headache, and concentration difficulties were the most common. Seronegative children had a higher number of individual symptoms. School absence and drop-out from leisure activities was substantial in both groups with higher numbers for the seronegative group. Self-reported health was low in both groups.

CONCLUSION: Children attending a specialist paediatric long COVID clinic experienced multiple symptoms and poor self-reported health. The symptomatology was similar regardless of serological status, implying multifactorial causes. A multidisciplinary assessment of this cohort was essential considering the broad spectrum of symptoms displayed and their substantial impact on everyday functioning.}, } @article {pmid39967901, year = {2024}, author = {Panesar, A and Gharanei, P and Khovanova, N and Young, L and Grammatopoulos, D}, title = {Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1477389}, pmid = {39967901}, issn = {1664-2392}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Thyroid Gland/physiopathology ; *SARS-CoV-2 ; Thyroid Diseases/complications/physiopathology ; Adult ; Post-Acute COVID-19 Syndrome ; Thyroid Function Tests ; Thyroid Hormones/blood ; Thyroiditis/etiology ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease. Long COVID may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.}, } @article {pmid39967803, year = {2025}, author = {Smadja, DM and Abreu, MM}, title = {Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1475376}, pmid = {39967803}, issn = {1662-4548}, abstract = {Neurodegenerative diseases (NDs) and Long COVID represent critical and growing global health challenges, characterized by complex pathophysiological mechanisms including neuronal deterioration, protein misfolding, and persistent neuroinflammation. The emergence of innovative therapeutic approaches, such as whole-body hyperthermia (WBH), offers promising potential to modulate underlying pathophysiological mechanisms in NDs and related conditions like Long COVID. WBH, particularly in fever-range, enhances mitochondrial function, induces heat shock proteins (HSPs), and modulates neuroinflammation-benefits that pharmacological treatments often struggle to replicate. HSPs such as HSP70 and HSP90 play pivotal roles in protein folding, aggregation prevention, and cellular protection, directly targeting pathological processes seen in NDs like Alzheimer's, Parkinson's, and Huntington's disease. Preliminary findings also suggest WBH's potential to alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent. Despite the absence of robust clinical trials, the therapeutic implications of WBH extend to immune modulation and the restoration of disrupted physiological pathways. However, the dual nature of hyperthermia's effects-balancing pro-inflammatory and anti-inflammatory responses-emphasizes the need for dose-controlled applications and stringent patient monitoring to minimize risks in vulnerable populations. While WBH shows potential interest, significant challenges remain. These include individual variability in response, limited accessibility to advanced hyperthermia technologies, and the need for standardized clinical protocols. Future research must focus on targeted clinical trials, biomarker identification, and personalized treatment strategies to optimize WBH's efficacy in NDs and Long COVID. The integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.}, } @article {pmid39966402, year = {2025}, author = {Appelman, B and Charlton, BT and Goulding, RP and Kerkhoff, TJ and Breedveld, EA and Noort, W and Offringa, C and Bloemers, FW and van Weeghel, M and Schomakers, B and Coelho, P and Posthuma, JJ and Aronica, E and Wiersinga, WJ and van Vugt, M and Wüst, RCI}, title = {Reply to: Should we be careful with exercise in post-exertional malaise after Long COVID?.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1725}, pmid = {39966402}, issn = {2041-1723}, } @article {pmid39966388, year = {2025}, author = {Saris, CGJ and van Engelen, BGM and Janssen, MCH and Kusters, B and Rodenburg, RJT and Sluijs, DE and Voet, NBM}, title = {Should we be careful with exercise in post-exertional malaise after long COVID?.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1724}, pmid = {39966388}, issn = {2041-1723}, } @article {pmid39966327, year = {2025}, author = {Barichello, T and Kluwe-Schiavon, B and Borba, LA and Pedro, LC and Niero, FS and Dos Santos, LN and Leonardo, LM and Ignácio, ZM and Morales, R and Ceretta, LB and Reus, GZ}, title = {Alterations in Gut Microbiome Composition and Increased Inflammatory Markers in Post-COVID-19 Individuals.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39966327}, issn = {1559-1182}, abstract = {Dysfunctions in the immune system and alterations in the microbiome composition following SARS-CoV-2 infection contribute to persistent neurological issues observed in long COVID-19 survivors. We hypothesize that alterations in the gut microbiome composition and peripheral inflammatory profile following COVID-19 may play pivotal roles in behavior changes among individuals experiencing long-term illness. This cross-sectional study included a sample of post-COVID-19 and non-COVID-19 subjects. We assessed the presence of psychiatric conditions utilizing standardized diagnostic criteria, Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression (HAM-D), Biological Rhythms in Neuropsychiatry Assessment Interview (BRIAN), and Functional Assessment Short Test (FAST). Plasma samples were analyzed to examine lipid and inflammatory profiles. Fecal samples were evaluated by 16S rRNA sequencing to identify the gut microbiome composition. Noteworthy findings include a significant increase in the myeloid progenitor inhibitory factor 1 (MPIF-1), interleukin (IL)-17, and triglyceride among post-COVID-19 individuals. While α-diversity in the gut microbiome composition showed no significant differences, β-diversity demonstrated a notable distinction between the healthy control and post-COVID-19 groups. Post-COVID-19 individuals exhibited a decreased abundance of phylum, class, and order of Verrucomicrobia, family, and genus of Akkermansia, a short-chain fatty acid producer and microbial group significantly associated with intestinal barrier homeostasis and the amelioration of metabolic diseases. No difference was found between the behavioral and clinical data. In post-COVID-19 individuals, there were elevated IL-17 and MPIF-1 levels, compared to non-COVID-19 individuals. Additionally, there were notable alterations in gut microbiome composition, as evidenced by changes in β-diversity and a decrease of Verrucomicrobia, family, and Akkermansia genus abundance.}, } @article {pmid39965723, year = {2025}, author = {Foreman, L and Child, B and Saywell, I and Collins-Praino, L and Baetu, I}, title = {Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {106067}, doi = {10.1016/j.neubiorev.2025.106067}, pmid = {39965723}, issn = {1873-7528}, abstract = {Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5,604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3,919 COVID-19 cases; 8,267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33% smaller among high CR individuals, and 33% greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.}, } @article {pmid39965512, year = {2025}, author = {Wallace, ZS and Lin, M and Srivatsan, S and King, A and Wang, X and Venkat, R and Kawano, Y and Negron, M and Hang, B and Schiff, A and Hanberg, J and Kowalski, EN and Johnson, C and Vanni, KMM and Williams, Z and Qian, G and Bolden, C and Mueller, KT and Bade, KJ and Saavedra, AA and Patel, NJ and Sparks, JA}, title = {Impact of long COVID on self-reported disease activity, disability, and quality of life in individuals with inflammatory arthritis.}, journal = {Seminars in arthritis and rheumatism}, volume = {71}, number = {}, pages = {152657}, doi = {10.1016/j.semarthrit.2025.152657}, pmid = {39965512}, issn = {1532-866X}, abstract = {BACKGROUND: People with inflammatory arthritis are at risk for poor COVID-19 outcomes. Little is known about the impact of long COVID on disease activity, disability, and quality of life in this population.

METHODS: We included participants with rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, or axial spondyloarthritis from RheumCARD, a prospective cohort study of people with rheumatic disease with and without prior COVID-19. Long COVID was defined as any symptom of acute COVID-19 for ≥90 days. Surveys include the Routine Assessment of Patient Index Data 3 (RAPID-3), modified health assessment questionnaire (MHAQ), short form-12 (SF-12), fatigue symptom inventory, and short form McGill Pain Questionnaire. We assessed the association of long COVID status with these outcomes.

RESULTS: We analyzed n = 59 with long COVID, n = 165 without long COVID, and n = 59 without prior COVID-19. The most common long COVID symptoms were fatigue (37.3 %), altered smell/taste (27.1 % and 25.4 %), difficulty breathing (20.3 %), and headache (15.3 %). Those with vs. without long COVID had worse mHAQ (median 0.4 vs. 0.1, p < 0.001), RAPID-3 (4.0 vs. 2.3, p = 0.0005), and physical and mental health (SF-12: 37.7 vs. 47.2, p = 0.0003 and 45.3 vs. 53.0, p = 0.003, respectively). Fatigue and pain were worse in those with vs. without long COVID (p < 0.05 for comparisons). Similar trends were observed in those with long COVID vs. those without prior COVID-19.

CONCLUSION: Long COVID may result in worsened pain, fatigue, and quality of life in people with inflammatory arthritis. Patient-reported outcomes should be interpreted with caution in people with inflammatory arthritis because of the impact of long COVID.}, } @article {pmid39964227, year = {2025}, author = {Gómez Bravo, R and Infanti, A and Billieux, J and Ritzen, M and Nischwitz, S and Erhardt, A and Staub, T and Huber, CG and Lang, U and Weidt, S and Wolff, K and Müller, J and Vögele, C and Benoy, C}, title = {Unmasking the Psychological Landscape of Long COVID: A Cluster-analytical Approach.}, journal = {Biopsychosocial science and medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/PSY.0000000000001380}, pmid = {39964227}, issn = {2998-8756}, support = {COVID-19/2021/16874342/Psy-Long-COVID//FNR/ ; }, abstract = {OBJECTIVE: Since the emergence of SARS-CoV-2, an increasing number of people report long-term physical and psychological impairments. Research on the immunological sequalae of long COVID (LC) is growing, though its relationship with mental health remains underexplored. We investigated the psychological impairments associated with LC, identify related psychological symptom clusters, and their relationship with physical symptoms and pandemic-related variables.

METHODS: Cross-sectional descriptive study, using an online questionnaire (September 2020 - December 2022) in German and French, assessing depression, anxiety, fatigue, stress, and somatic symptoms. Clusters were identified using hierarchical and machine learning techniques (Kmeans and AffinityPropagation) and compared based on LC symptoms, past physical and mental health, substance use, COVID-19 variant, and family dynamics.

RESULTS: Among 1218 LC participants (78.7% female), four clusters were identified using AffinityPropagation: (1) low anxiety, depression, and somatoform symptoms, (2) low anxiety and depression but moderate somatoform symptoms, (3) high anxiety and depression with high somatoform symptoms, and (4) high anxiety and depression with moderate somatoform symptoms. Cluster 3 reported the most severe physical and neurological symptoms, the largest life impact (including relationship deterioration and professional difficulties) and the highest prevalence of past mental disorders (depression and PTSD). Cluster 1 reported the least symptoms.

CONCLUSIONS: LC significantly impacts mental health, particularly through increased anxiety, depression, and somatoform symptoms, especially in patients with severe LC physical symptoms. Psychological interventions targeting distinct symptom clusters may improve both mental and physical outcomes. Early mental health screening and tailored interventions are recommended for LC assessment and treatment.}, } @article {pmid39963121, year = {2024}, author = {Marbaix, S and Simoens, S and Clevenbergh, P and Van Bleyenbergh, P and Liberman, K and Dehenau, D}, title = {Real-world cost-effectiveness of nirmatrelvir-ritonavir as treatment for SARS-CoV-2 infection in the Belgian setting with omicron variant.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1432821}, pmid = {39963121}, issn = {2296-2565}, mesh = {Humans ; *Cost-Benefit Analysis ; *Ritonavir/therapeutic use/economics ; Belgium ; *COVID-19 Drug Treatment ; *SARS-CoV-2 ; *Antiviral Agents/therapeutic use/economics ; *Quality-Adjusted Life Years ; Hospitalization/economics/statistics & numerical data ; Male ; Female ; Drug Combinations ; COVID-19/economics ; Middle Aged ; }, abstract = {BACKGROUND: Nirmatrelvir-ritonavir is an oral treatment for SARS-CoV-2 infection in patients who are at high risk of developing severe COVID-19 disease. This antiviral has proven to significantly reduce the risk of hospitalization and death compared to no anti-SARS-CoV-2 treatment in this target population. This paper aims to assess the cost-effectiveness of nirmatrelvir-ritonavir in Belgium using real-world evidence.

METHODS: A static decision tree model was developed to capture the health progression of patients infected with the SARS-CoV-2 virus. Outcomes were expressed in Quality Adjusted-Life Years (QALYs), hospitalizations, Intensive Care Unit (ICU) admissions, deaths and Long Covid cases, derived from epidemiological data over the first full year of the Omicron variant's circulation (2022). Costs were calculated for the year 2023 from the healthcare payer's perspective. Extensive sensitivity analyses were conducted to test the robustness of the cost-effectiveness results.

RESULTS: In a cohort of 1,000 patients, treatment with nirmatrelvir-ritonavir is projected to save 95 QALYs and €82,658 compared to no anti-SARS-CoV-2 treatment over a lifetime horizon. These savings primarily stem from the reduction in hospitalizations among vulnerable patients who typically require a longer recovery time. The analysis also indicates 5 fewer ICU admissions and 8 fewer premature deaths per 1,000 infected patients.

CONCLUSION: In the context of Omicron SARS-CoV-2 infection, administering nirmatrelvir-ritonavir to patients at high risk of severe disease improves health outcomes and reduces costs. Nirmatrelvir-ritonavir is 100% likely to be cost-effective at a willingness to pay of €2,000 per QALY.}, } @article {pmid39961398, year = {2025}, author = {Wilkinson, S and Wilkinson, J and Grace, A and Lyon, D and Mellor, M and Yunus, T and Manning, J and Dinsdale, G and Berks, M and Knight, S and Bakerly, N and Gebril, A and Dark, P and Herrick, A and Taylor, C and Dickinson, M and Murray, A}, title = {Imaging the microvasculature using nailfold capillaroscopy in patients with coronavirus disease-2019; A cross-sectional study.}, journal = {Microvascular research}, volume = {}, number = {}, pages = {104796}, doi = {10.1016/j.mvr.2025.104796}, pmid = {39961398}, issn = {1095-9319}, abstract = {OBJECTIVES: It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantitative nailfold capillaroscopy system in identifying microvascular changes in those confirmed with or having had COVID-19.

METHODS: Ninety-seven participants were enrolled into this study and grouped as follows: 52 participants with acute COVID-19 (further grouped by disease severity) and 45 participants with convalescent COVID-19 (further grouped into long COVID i.e. symptoms beyond 12 weeks, and fully recovered). Nailfold capillaroscopy images were obtained from the bilateral ring fingers using a Dino-Lite CapillaryScope 200 Pro, a small USB handheld microscope. Images were assessed quantitatively using bespoke automated measurement software and the number of haemorrhages noted for each participant.

RESULTS: Capillaries were predominantly 'normal' in appearance with narrow capillary loops and evenly distributed, but with an increased number of haemorrhages (40 % in the convalescent group and 17 % in the acute group, p = 0.007). There was no statistically significant difference in the mean width of capillaries (20.9-21.8 μm) or vessel density (9.6-9.9 caps/mm; acute and convalescent group, respectively).

CONCLUSIONS: This study has demonstrated the feasibility of nailfold capillaroscopy at the critical care bedside. Capillary structure appeared normal across all groups of individuals affected by COVID-19. Although the small differences in the microvasculature in recovered patients compared to in acutely unwell patients may suggest delayed structural change due to COVID-19, these differences are unlikely to be clinically relevant. Longitudinal studies would be required to explore this in more detail.}, } @article {pmid39961083, year = {2025}, author = {Hemmi, M and Kanda, N and Nakamura, K and Suganuma, S and Kawabata, K and Kato, H and Ichihara, N and Asami, T and Ide, K and Muto, Y and Hori, M and Iba, A and Hosozawa, M and Iso, H}, title = {The relationship between the phenotype of long COVID symptoms and one-year psychosocial outcomes: an exploratory clustering analysis.}, journal = {Psychology, health & medicine}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/13548506.2025.2465654}, pmid = {39961083}, issn = {1465-3966}, abstract = {The impact of Coronavirus Disease 2019 (COVID-19) is not limited to acute symptoms; it also extends to post-infection sequelae, such as long COVID and post-COVID conditions. These conditions are characterized by various symptoms, such as malaise, fatigue, and cognitive dysfunction, and are considered to reflect different underlying pathologies. Using a cluster analysis, we hypothesized that long COVID may have different psychosocial outcomes depending on the phenotype. This study is based on the COVID-19 RECOVERY STUDY II (CORES II) conducted in 20 centers in Japan. CORES II included patients aged 20 years and older who were hospitalized and discharged alive between April and September 2021. In CORES II, information collected at hospitalization was followed by an investigation one year after diagnosis into post-infection symptoms, physical and mental health, and patients' social circumstances. Long COVID symptoms, based on symptoms one month after infection, and psychosocial well-being, including anxiety, depression, post-traumatic stress disorder, and quality of life (QOL), one year after onset were assessed via questionnaires provided one year after diagnosis. We performed a cluster analysis based on long COVID symptoms. We also compared the psychosocial status between clusters. We identified five clusters of symptoms in 746 patients. These clusters were characterized by severe multi-organ dysfunction, olfactory and gustatory disturbances, shortness of breath, muscle weakness, and hair loss. The severe multi-organ dysfunction cluster included a large number of patients with malaise and who were more likely to have a poor psychosocial status one year after onset. In addition, the olfactory and gustatory disturbance cluster appeared to have the second highest depression and anxiety scores after the multi-organ dysfunction cluster. The results obtained on the five-symptom clusters suggest that the multi-organ dysfunction phenotype with malaise and olfactory and gustatory disturbances has psychosocial consequences. Patients with these phenotypes require more extensive follow-ups and interventions.}, } @article {pmid39960888, year = {2025}, author = {Chang, CC and Li, YH and Chang, ST and Chen, HH}, title = {Impact of Intravenous Laser Irradiation of Blood on Cognitive Function and Molecular Pathways in Long COVID Patients: A Pilot Study.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {}, number = {}, pages = {}, doi = {10.1093/qjmed/hcaf050}, pmid = {39960888}, issn = {1460-2393}, abstract = {BACKGROUND: Long COVID presents persistent neurological symptoms, including brain fog, with limited therapeutic options. Intravenous Laser Irradiation of Blood (ILIB) has been proposed as a potential intervention. This pilot study explores the efficacy of ILIB in alleviating brain fog symptoms and examines the underlying molecular mechanisms.

AIM: To evaluate the effectiveness of ILIB in improving cognitive function in long COVID patients with brain fog and to investigate the molecular pathways involved.

DESIGN: A prospective, single-center pilot study involving six long COVID patients with brain fog who underwent ILIB therapy.

METHODS: Patients received 30 ILIB sessions over eight weeks. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Athens Insomnia Scale (AIS) at baseline, post-treatment, and one-month follow-up. RNA sequencing and pathway enrichment analyses (KEGG, Gene Ontology) identified differentially expressed genes and molecular pathways influenced by ILIB.

RESULTS: MoCA and AIS scores significantly improved post-ILIB, suggesting enhanced cognitive function and sleep quality. RNA sequencing revealed 141 upregulated and 130 downregulated genes. Upregulated pathways were associated with mitochondrial electron transport and oxidative phosphorylation, while immune response and inflammatory pathways were downregulated. Notably, the glutathione metabolism pathway was significantly altered, suggesting reduced oxidative stress.

CONCLUSIONS: ILIB shows potential in alleviating brain fog symptoms in long COVID patients, possibly through modulation of oxidative stress, mitochondrial function, and inflammation. However, larger randomized controlled trials are needed to confirm these findings and establish ILIB as a viable therapeutic option.}, } @article {pmid39960432, year = {2025}, author = {Syed, AM and Karius, AK and Ma, J and Wang, PY and Hwang, PM}, title = {Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Physiology (Bethesda, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiol.00056.2024}, pmid = {39960432}, issn = {1548-9221}, support = {HL005101//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; }, abstract = {ME/CFS is a debilitating multisystem disorder of unclear etiology that affects many individuals worldwide. One of its hallmark symptoms is prolonged fatigue following exertion, a feature also observed in long COVID, suggesting an underlying dysfunction in energy production in both conditions. Here, mitochondrial dysfunction and its potential pathogenetic role in these disorders are reviewed.}, } @article {pmid39960228, year = {2025}, author = {Ryan, SJ and Wong, C and Sinclair, A and Ni, E and Wang, D}, title = {Living with Long COVID: A Narrative Study.}, journal = {Occupational therapy in health care}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/07380577.2025.2466223}, pmid = {39960228}, issn = {1541-3098}, abstract = {This qualitative narrative study describes the stories of persons with Long COVID. Four individuals participated in semi-structured interviews with photo elicitation. Thematic analysis yielded six themes: symptom complexity, deep emotional impact, changes to daily life, not being believed, navigating healthcare alone, and positive influence of social support illustrating that persons with Long COVID experience major changes in their bodies, routines, and relationships. The results can inform occupational therapy services by encouraging occupational therapy practitioners to pursue updated Long COVID-specific continuing education and address the functional limitations, role competencies, support systems, and life priorities of these clients.}, } @article {pmid39958473, year = {2025}, author = {Brambilla, M and Fumoso, F and Conti, M and Becchetti, A and Bozzi, S and Mencarini, T and Agostoni, P and Mancini, ME and Cosentino, N and Bonomi, A and Nallio, K and Galotta, A and Pengo, M and Tortorici, E and Bosco, M and Cernigliaro, F and Pinna, C and Andreini, D and Camera, M}, title = {Low-Grade Inflammation in Long COVID Syndrome Sustains a Persistent Platelet Activation Associated With Lung Impairment.}, journal = {JACC. Basic to translational science}, volume = {10}, number = {1}, pages = {20-39}, pmid = {39958473}, issn = {2452-302X}, abstract = {In the present study, we provide evidence on the potential mechanisms involved in the residual pulmonary impairment described in long COVID syndrome. Data highlight that lung damage is significantly associated with a proinflammatory platelet phenotype, characterized mainly by the formation of platelet-leukocyte aggregates. In ex vivo experiments, long COVID plasma reproduces the platelet activation observed in vivo and highlights low-grade inflammation as a potential underpinning mechanism, exploiting a synergistic activity between C-reactive protein and subthreshold concentrations of interleukin-6. The platelet-activated phenotype is blunted by anti-inflammatory and antiplatelet drugs, suggesting a potential therapeutic option in this clinical setting.}, } @article {pmid39958471, year = {2025}, author = {Roweth, HG}, title = {The Lung and Winding Road: Inflammation-Driven Platelet Reactivity in Long COVID.}, journal = {JACC. Basic to translational science}, volume = {10}, number = {1}, pages = {40-42}, pmid = {39958471}, issn = {2452-302X}, } @article {pmid39958365, year = {2025}, author = {Dochnal, SA and Cohen, SP and Hutchinson, MR and Miller, YI and Yaksh, TL}, title = {Virally-initiated pain states: phenotypes, mechanisms, and future directions.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {6}, number = {}, pages = {1527106}, pmid = {39958365}, issn = {2673-561X}, abstract = {The recent SARS-CoV-2 pandemic has underscored the significance of viral infections, affecting billions of lives and costing trillions of dollars globally. Even beyond SARS-CoV-2, common infections with viruses like influenza, HIV, and herpesviruses have profound impacts beyond their typical manifestations, often triggering acute and chronic pain syndromes that can be life-altering. These virally induced pain states can arise through direct viral replication within neurons, or indirectly, via immune responses to infection in both the contexts of afferent signaling in the dorsal root ganglion (DRG) or subsequent higher order integration in intracranial systems. Varicella-zoster virus (VZV), influenza virus, and SARS-CoV-2 each provide a unique lens through which to examine the interplay between viral activity and pain. This perspective paper is not meant to be an exhaustive review of virally-induced neuropathic pain states. It seeks to explore curated aspects of the complexities of these pain states, identify research gaps, and suggest solutions using nanoscale molecular understanding and psychoneuroimmunological and biopsychosocial frameworks. Each subheading is accompanied by a list of related issues for study which we think will lead to advances in our understanding of the vexing pain phenotype associated with viral infection.}, } @article {pmid39957507, year = {2025}, author = {Troll, M and Li, M and Chand, T and Machnik, M and Rocktäschel, T and Toepffer, A and Ballez, J and Finke, K and Güllmar, D and Reichenbach, JR and Walter, M and Besteher, B}, title = {Altered corticostriatal connectivity in long-COVID patients is associated with cognitive impairment.}, journal = {Psychological medicine}, volume = {55}, number = {}, pages = {e49}, doi = {10.1017/S0033291725000054}, pmid = {39957507}, issn = {1469-8978}, mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/physiopathology/etiology/diagnostic imaging ; *COVID-19/complications/physiopathology/psychology ; *Magnetic Resonance Imaging ; Middle Aged ; Caudate Nucleus/physiopathology/diagnostic imaging ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Cerebral Cortex/physiopathology/diagnostic imaging ; SARS-CoV-2 ; Case-Control Studies ; Corpus Striatum/physiopathology/diagnostic imaging ; Gyrus Cinguli/physiopathology/diagnostic imaging ; Connectome ; }, abstract = {BACKGROUND: The COVID-19 pandemic has had a significant impact on the health of millions of people worldwide, and many manifest new or persistent symptoms long after the initial onset of the infection. One of the leading symptoms of long-COVID is cognitive impairment, which includes memory loss, lack of concentration, and brain fog. Understanding the nature and underlying mechanisms of cognitive impairment in long-COVID is important for developing preventive and therapeutic interventions.

METHODS: Our present study investigated functional connectivity (FC) changes in patients with long-COVID and their associations with cognitive impairment. Resting-state functional MRI data from 60 long-COVID patients and 52 age- and sex-matched healthy controls were analyzed using seed-based functional connectivity analysis.

RESULTS: We found increased FC between the right caudate nucleus and both the left and right precentral gyri in long-COVID patients compared with healthy controls. In addition, elevated FC was observed between the right anterior globus pallidus and posterior cingulate cortex as well as the right temporal pole in long-COVID patients. Importantly, the magnitude of FC between the caudate and the left precentral gyrus showed a significant negative correlation with Montreal Cognitive Assessment (MoCA) scores and a negative correlation with Trail Making Test B performance in the patient group.

CONCLUSION: Patients with long-COVID present enhanced FC between the caudate and the left precentral gyrus. Furthermore, those FC alterations are related to the severity of cognitive impairment, particularly in the domain of executive functions.}, } @article {pmid39956285, year = {2025}, author = {Talwar, S and Harker, JA and Openshaw, PJM and Thwaites, RS}, title = {Autoimmunity in Long-COVID.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.02.005}, pmid = {39956285}, issn = {1097-6825}, abstract = {Long-COVID (also termed Post-Acute Sequelae of SARS-CoV-2 or PASC) affects up to 10% of people recovering from SARS-CoV-2 infection. Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, an incomplete understanding of pathogenesis, and the lack of validated treatments. In terms of pathogenesis, hypothesised causes include viral persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show pre-existing and/or de novo production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long-COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long-COVID.}, } @article {pmid39956089, year = {2025}, author = {Smith, DS and Postma, M and Fisman, D and Mould-Quevedo, J}, title = {Cost-effectiveness models assessing COVID-19 booster vaccines across eight countries: A review of methods and data inputs.}, journal = {Vaccine}, volume = {51}, number = {}, pages = {126879}, doi = {10.1016/j.vaccine.2025.126879}, pmid = {39956089}, issn = {1873-2518}, abstract = {Coronavirus disease 2019 (COVID-19) continues to cause serious health consequences globally. Policy makers now assess cost effectiveness (CE) when evaluating COVID-19 vaccines. A targeted literature review was performed to examine recent CE evidence for COVID-19 vaccines, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions from pandemic to endemic, to identify best practices. Data were from large EU countries (UK, Spain, Germany, France, and Italy), US, Canada, and Australia. Nine CE studies met the inclusion criteria. Studies evaluated booster vaccination, and mainly considered mRNA vaccines. CE studies reported that COVID-19 vaccines provided health benefits and were cost-effective or showed cost-savings. Benefits were more pronounced in older and high-risk populations based on higher rates of COVID-19 hospitalization and death. CE findings were most sensitive to estimates of incidence of COVID-19, SARS-CoV-2 transmissibility, vaccine effectiveness, waning/duration of vaccine protection, and hospitalization costs. Most data inputs were sourced from real-world evidence (RWE). Lack of inclusion of some parameters, such as transmission modeling, productivity losses, and the impact of long COVID may undervalue COVID-19 vaccines. As SARS-CoV-2 evolves and COVID-19 vaccines are updated, continuous generation of RWE is needed to demonstrate the CE of COVID-19 vaccines in an ongoing manner.}, } @article {pmid39955111, year = {2025}, author = {Ketharanathan, N and Dulfer, K and de Hoog, M and Otten, M and Buysse, C}, title = {Generation C: the scope and effects of paediatric long COVID.}, journal = {Lancet (London, England)}, volume = {405}, number = {10478}, pages = {541-542}, doi = {10.1016/S0140-6736(24)02622-9}, pmid = {39955111}, issn = {1474-547X}, } @article {pmid39954574, year = {2025}, author = {Soltsov, M and Jang, DH and Kim, JH and Keenan, A and Pain, K and Jaywant, A and Stilling, J}, title = {Understanding neural mechanisms and the use of targeted non-invasive brain stimulation for treatment of post-stroke fatigue: A scoping review.}, journal = {Journal of the neurological sciences}, volume = {470}, number = {}, pages = {123399}, doi = {10.1016/j.jns.2025.123399}, pmid = {39954574}, issn = {1878-5883}, abstract = {BACKGROUND: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF.

METHODS: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: >18 years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions.

RESULTS: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF.

CONCLUSION: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF.}, } @article {pmid39953331, year = {2025}, author = {Garbsch, R and Mooren, FC and Schmitz, B}, title = {No impairment of maximal oxygen uptake in patients diagnosed with long COVID?.}, journal = {European journal of applied physiology}, volume = {}, number = {}, pages = {}, pmid = {39953331}, issn = {1439-6327}, } @article {pmid39952011, year = {2025}, author = {Schurr, M and Graf, J and Junne, F and Giel, KE}, title = {Psychotherapy in patients with long/post-COVID - A systematic review on the feasibility, acceptability, safety, and efficacy of available and emerging interventions.}, journal = {Journal of psychosomatic research}, volume = {190}, number = {}, pages = {112048}, doi = {10.1016/j.jpsychores.2025.112048}, pmid = {39952011}, issn = {1879-1360}, abstract = {BACKGROUNDS: There is an urgent need for effective treatments for patients with long/post-COVID. Current recommendations for management favor a multimodal approach including psychotherapy and emphasize that interventions should also consider the mental health impact of living with long/post-COVID. This systematic review synthesizes psychotherapeutic interventions that currently target long/post-COVID complaints and summarizes data on the feasibility, acceptability, safety, and efficacy of psychotherapy for patients with long/post-COVID.

METHODS: This systematic review was conducted according to the PRISMA statement. Studies were retrieved from three databases (PubMed, PsycInfo, Web of Science) and independently assessed by two raters. Studies investigating patients of any age suffering from long/post-COVID were included if the intervention involved psychotherapeutic treatment and changes in long/post-COVID symptoms were reported. The review has been pre-registered on PROSPERO.

RESULTS: A total of 12 studies were included in the analysis. Of these, 10 were multimodal approaches with integrated psychotherapeutic interventions, and two were studies on stand-alone psychotherapy. The majority of studies were uncontrolled and demonstrate pre-post improvements in a range of long/post-COVID symptoms. Only one RCT could be identified, which supports the benefit of CBT for COVID-related fatigue. It was not possible to draw general conclusions regarding the efficacy of psychotherapy for long/post-COVID. However, data on feasibility, acceptability, and safety support the potential of psychotherapy as a treatment approach for long/post-COVID.

CONCLUSION: Future studies investigating the potential of psychotherapy approach for long/post-COVID which go beyond the pilot stage are needed to systematically assess feasibility, acceptability, safety, and efficacy in large-scale confirmatory trials.}, } @article {pmid39950320, year = {2025}, author = {Cappelletti, G and Brambilla, L and Strizzi, S and Limanaqi, F and Melzi, V and Rizzuti, M and Nizzardo, M and Saulle, I and Trabattoni, D and Corti, S and Clerici, M and Biasin, M}, title = {iPSC-derived human cortical organoids display profound alterations of cellular homeostasis following SARS-CoV-2 infection and Spike protein exposure.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {4}, pages = {e70396}, pmid = {39950320}, issn = {1530-6860}, support = {//Dino Ferrari Center/ ; 13-CUP-G43C2200260007-INF-ACT//PNRR-Spoke/ ; }, mesh = {Humans ; *Organoids/virology/metabolism ; *Induced Pluripotent Stem Cells/metabolism/virology ; *SARS-CoV-2/physiology/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; *COVID-19/metabolism/virology/pathology ; *Homeostasis ; Cerebral Cortex/metabolism/virology/cytology ; Angiotensin-Converting Enzyme 2/metabolism/genetics ; Neuropilin-1/metabolism/genetics ; }, abstract = {COVID-19 commonly leads to respiratory issues, yet numerous patients also exhibit a diverse range of neurological conditions, suggesting a detrimental impact of SARS-CoV-2 or the viral Spike protein on the central nervous system. Nonetheless, the molecular pathway behind neurological pathology and the presumed neurotropism of SARS-CoV-2 remains largely unexplored. We generated human cortical organoids (HCOs) derived from human induced pluripotent stem cells (hiPSC) to assess: (1) the expression of SARS-CoV-2 main entry factors; (2) their vulnerability to SARS-CoV-2 infection; and (3) the impact of SARS-CoV-2 infection and exposure to the Spike protein on their transcriptome. Results proved that (1) HCOs express the main SARS-CoV-2 receptors and co-receptors; (2) HCOs may be productively infected by SARS-CoV-2; (3) the viral particles released by SARS-CoV-2-infected HCOs are able to re-infect another cellular line; and (4) the infection resulted in the activation of apoptotic and stress pathways, along with inflammatory processes. Notably, these effects were recapitulated when HCOs were exposed to the Spike protein alone. The data obtained demonstrate that SARS-CoV-2 likely infects HCOs probably through the binding of ACE2, CD147, and NRP1 entry factors. Furthermore, exposure to the Spike protein alone proved sufficient to disrupt their homeostasis and induce neurotoxic effects, potentially contributing to the onset of long-COVID symptoms.}, } @article {pmid39949717, year = {2025}, author = {Salmam, I and Perreault, K and Best, KL and Zahouani, I and Drouin, G and Tittley, J and Desmeules, F and Campeau-Lecours, A and Beaulieu-Bonneau, S and Paquette, JS and Deslauriers, S and Brouillard, SM and Lepage, K and Roy, JS}, title = {Physical impairments in individuals with Long COVID.}, journal = {Frontiers in sports and active living}, volume = {7}, number = {}, pages = {1511942}, pmid = {39949717}, issn = {2624-9367}, abstract = {OBJECTIVE: The primary objective was to compare the physical capacities of individuals with Long COVID [Long COVID group (LCG)] to those who had COVID-19 but did not develop persistent symptoms [short COVID group (SCG)], and to individuals without a history of COVID-19 [control group (CG)]. The secondary objectives were to provide a comprehensive profile of sociodemographic and COVID-19 history of individuals with Long COVID, considering factors such as sex, gender, hospitalization, time since onset, and comorbidities, and b) identify self-reported and objective clinical measures explaining health-related quality of life (HRQoL) in individuals with Long COVID.

METHODS: A total of 120 adults were included in each of the groups. Participants completed self-reported assessments covering HRQoL, comorbidities, pain, sleep, and fatigue. Physical assessments included handgrip strength (HGS), Short Physical Performance Battery (SPPB), 6-minute-walk-test (6MWT), perceived exertion during the 6MWT (Modified-Borg Scale), and daily step count during a 7-day period.

RESULTS: Mean age (mean [SD]) for LCG, SCG, and CG was 44.2 [11.2], 42.1 [16.4], and 46[15.9], respectively. LCG showed significantly higher pain, comorbidities, and fatigue, along with lower HRQoL and sleep quality compared to the other groups. HGS, SPPB, and 6MWT performance were also significantly lower in LCG, while perceived exertion during 6MWT was higher. Finally, the number of steps per day was significantly lower in LCG. Higher prevalence of obesity and comorbidities were identified among those hospitalized after COVID-19. Fatigue, pain, comorbidities, and Step count were the variables explaining HRQoL for LCG (R2: 0.58; F = 35.9).

CONCLUSION: Long COVID individuals, on average 329 [146] days post-infection, experience enduring physical and health-related challenges, with significant implications for their overall well-being.}, } @article {pmid39949480, year = {2025}, author = {Georgopoulos, AP and James, LM and Peterson, PK}, title = {Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID.}, journal = {Journal of immunological sciences}, volume = {9}, number = {1}, pages = {1-3}, pmid = {39949480}, issn = {2578-3009}, abstract = {Here we offer a perspective on recent findings of persistent SARS-CoV-2 antigens in Long COVID[1] through the lens of immunogenetic risk and protection, namely in the context of the fundamental role of Human Leukocyte Antigen (HLA) in eliminating viral infections. Specifically, we attribute the persistence of viral antigens to the lack or weak protection conferred by HLA against SARS-CoV-2 in individuals carrying HLA alleles with low binding affinities to the virus. We suggest that determining the HLA Class I and II makeup of Long COVID patients will provide valuable new information in elucidating the cause for antigen persistence underlying the development of Long COVID and pave the way for successful interventions.}, } @article {pmid39948466, year = {2025}, author = {Yang, J and Rai, KK and Alfred, T and Massey, L and Massey, O and McGrath, L and Andersen, KM and Tritton, T and Tsang, C and Butfield, R and Reynard, C and Mendes, D and Nguyen, JL}, title = {The impact of COVID vaccination on incidence of long COVID and healthcare resource utilisation in a primary care cohort in England, 2021-2022.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {214}, pmid = {39948466}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; England/epidemiology ; Male ; Female ; *Primary Health Care/statistics & numerical data ; Middle Aged ; Aged ; Incidence ; Adult ; Cohort Studies ; *COVID-19 Vaccines/administration & dosage ; *SARS-CoV-2/immunology ; *Vaccination/statistics & numerical data ; Patient Acceptance of Health Care/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Young Adult ; Health Resources/statistics & numerical data ; Adolescent ; }, abstract = {BACKGROUND: Long COVID, a diverse set of symptoms that persist after a minimum of 4 weeks from the initial SARS-CoV-2 infection, has posed substantial burden to healthcare systems. There is some evidence that COVID-19 vaccination may be associated with lower risk of long COVID. However, little is known about the association between vaccination status and long COVID-associated healthcare resource utilisation (HCRU) and costs.

METHODS: We conducted a cohort study using primary care electronic health record data in England from the Clinical Practice Research Datalink (CPRD) Aurum dataset linked to Hospital Episode Statistics where available. Adult (≥ 18 years) patients were indexed on a COVID-19 diagnosis between 1st March 2021 and 1st December 2021. Vaccination status was assessed at index: unvaccinated or completed primary series (two doses for immunocompetent and three doses for immunocompromised patients). Covariate balance was conducted using entropy balancing. Weighted multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) for incident long COVID, and separately long COVID primary care resource use, by vaccination status. Patients were followed up to a maximum of 9-months post index.

RESULTS: A total of 35,713 patients who had completed primary series vaccination, and 75,522 unvaccinated patients were included. The weighted and adjusted IRR for long COVID among patients vaccinated with the primary series compared to being unvaccinated was 0.81 (95% CI: 0.77-0.86) in the overall cohort, 0.83 (95% CI: 0.78-0.88) in the immunocompetent cohort and 0.28 (95% CI: 0.13-0.58) in the immunocompromised cohort. Among those with long COVID, there was no association between the rate of primary care consultations and vaccination status in the overall and immunocompetent cohorts. Cost of primary care consultations was greater in the unvaccinated group than for those who completed primary series.

CONCLUSION: Vaccination against COVID-19 may reduce the risk of long COVID in both immunocompetent and immunocompromised patients. However, no association was found between frequency of primary care visits and vaccination among patients diagnosed in 2021. Future studies with larger sample size, higher vaccine uptake, and longer study periods during the pandemic are needed to further quantify the impact of vaccination on long COVID.}, } @article {pmid39947498, year = {2025}, author = {Wang, L and Yang, W}, title = {Higher Prevalence of Long COVID Observed in Cancer Survivors: Insights from a US Nationwide Survey.}, journal = {Annals of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.annepidem.2025.02.004}, pmid = {39947498}, issn = {1873-2585}, abstract = {BACKGROUND: Cancer and cancer treatments can weaken the body's immune system, making cancer patients particularly vulnerable to COVID-19. While evidence suggests that cancer patients may be at increased risk for severe outcomes after COVID-19 infection, there is a lack of population-based studies comparing long COVID prevalence between cancer survivors and non-cancer individuals.

METHODS: We utilized data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), analyzing a sample of 120,658 U.S. adults who had tested positive for COVID-19. Long COVID was defined as the presence of COVID-19 symptoms lasting three months or longer. The weighted prevalence of long COVID was compared between cancer survivors and non-cancer individuals. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Multiple imputation was employed to address missing data on COVID-19 vaccination.

RESULTS: Among 17,362 cancer survivors who tested positive for COVID-19, 4,009 reported having long COVID (weighted prevalence = 24.0%), compared to a weighted prevalence of 21.6% in non-cancer individuals (p < 0.001). After controlling for covariates and accounting for the complex sampling design, the adjusted OR was 1.17 (95% CI = 1.06-1.30, p = 0.002). In participants under 45 years old, cancer survivors had a notably higher prevalence of long COVID compared to non-cancer individuals (32.1% vs. 21.3%, p < 0.001), with an adjusted OR of 1.33 (95% CI = 1.07-1.66, p = 0.012). In participants aged 45 and above, the prevalence difference was not significant (22.7% vs. 21.9%, p = 0.324), with an adjusted OR of 1.14 (95% CI = 1.02-1.27, p = 0.024). Regarding the association of COVID-19 vaccination with long COVID, four or more doses were linked to a significant reduced odds of long COVID among cancer survivors (adjusted OR=0.55, 95%CI = 0.34-0.88, p = 0.013).

CONCLUSIONS: Cancer survivors are observed to have higher odds of developing long COVID, particularly younger survivors. The association of COVID-19 vaccination with long COVID varies between cancer survivors and non-cancer individuals, with cancer survivors requiring more doses to achieve significant reduction in the odds of long COVID.}, } @article {pmid39947217, year = {2025}, author = {Proal, AD and Aleman, S and Bomsel, M and Brodin, P and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Hewitt, SM and Iwasaki, A and Krumholz, HM and Locci, M and Marconi, VC and Mehandru, S and Muller-Trutwin, M and Painter, MM and Pretorius, E and Price, DA and Putrino, D and Qian, Y and Roan, NR and Salmon, D and Tan, GS and VanElzakker, MB and Wherry, EJ and Van Weyenbergh, J and Yonker, LM and Peluso, MJ}, title = {Targeting the SARS-CoV-2 reservoir in long COVID.}, journal = {The Lancet. Infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/S1473-3099(24)00769-2}, pmid = {39947217}, issn = {1474-4457}, abstract = {There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.}, } @article {pmid39946348, year = {2025}, author = {Ismail, H and Huam, ZS and Yew, SQ and Ahmad, H and David, CCH and Baharudin, MH and Muhd Aris, NA}, title = {Sickness absenteeism among nurses after the COVID-19 pandemic: A study protocol.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0314763}, doi = {10.1371/journal.pone.0314763}, pmid = {39946348}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Malaysia/epidemiology ; Cross-Sectional Studies ; *Absenteeism ; Surveys and Questionnaires ; Nurses/psychology ; SARS-CoV-2/isolation & purification ; Female ; Male ; Pandemics ; Risk Factors ; Adult ; Anxiety/epidemiology ; Depression/epidemiology ; Prevalence ; Workload/psychology ; Sick Leave/statistics & numerical data ; Stress, Psychological/epidemiology ; Occupational Stress/epidemiology ; }, abstract = {INTRODUCTION: Sickness absenteeism among the nurses in Malaysia is not fully understood. Complicated with the increase in workload and mental stress during the COVID-19 pandemic and the manifestation of long COVID-19 symptoms, there is a need for an updated insight on the prevalence and the risk factors of sickness absenteeism among nurses in Malaysia. As such, we designed a study protocol that assess the prevalence and risk factors of sickness absenteeism among nurses in Malaysia in the post-COVID-19 pandemic era.

MATERIALS AND METHODS: This is a correlational cross-sectional study. The sociodemographic and clinical questionnaire, sickness absenteeism questionnaire, job characteristics questionnaire, Demand-Control-Support Questionnaire (DCSQ), Work-Related Strain Inventory (WRSI), Work and Family Conflict Scale (WAFCS), the COVID-19-related workplace worries questionnaire, as well as the Depression, Anxiety, and Stress (DASS-21) questionnaire will be randomly distributed to 166 nurses from October 2024 to May 2025.

DISCUSSION: While physical illnesses, psychological disorders, job-related factors, and sociodemographic factors have been identified as risk factors to sickness absenteeism among healthcare professionals in general, the role of these risk factors in causing sickness absenteeism among the nurses remains unclear. Additionally, the increased stress and workload faced by nurses during the COVID-19 pandemic, as well as post-acute COVID-19 syndrome, may have further impacted sickness absenteeism.

CONCLUSION: By examining the various risk factors of sickness absenteeism, especially in the post-COVID-19 pandemic era, this research will inform future targeted interventions to reduce sickness absenteeism among Malaysian nurses and its associated consequences.}, } @article {pmid39944605, year = {2025}, author = {Zhang, T and Li, Z and Mei, Q and Walline, JH and Zhang, Z and Liu, Y and Zhu, H and Du, B}, title = {Cardiovascular outcomes in long COVID-19: a systematic review and meta-analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1450470}, pmid = {39944605}, issn = {2297-055X}, abstract = {INTRODUCTION: There is growing evidence that patients with SARS-CoV-2 (The severe acute respiratory syndrome coronavirus 2) may have a variety of cardiovascular complications in the post-acute phase of COVID-19, but these manifestations have not yet been comprehensively characterized.

METHODS: We performed a systematic review and meta-analysis of primary research papers which evaluated individuals at least four weeks after confirmed COVID-19 diagnosis and reported on cardiovascular disease prevalence. Systematic search conducted without language restrictions from December 1, 2019 to June 31, 2022 on PubMed, EMBASE, Web of Science, Cochrane library, ProQuest Coronavirus Research Database, COVID-19 Living Overview of the Evidence (L-OVE) subset of Episteminokos and the World Health Organization (WHO) Covid-19 databases. Study was reported according to MOOSE-lists and the PRISMA guidelines. The risk of bias was identified using the Newcastle-Ottawa Scale (NOS) for observational studies. Random-effects meta-analyses examined the pooled risk difference in the prevalence of each symptom or symptom combination in cases with confirmed SARS-coV-2 infection compared with controls.

RESULTS: Eight cohort studies were eligible, including nearly 10 million people. Long COVID-19 was associated with a higher risk of thromboembolic disorders [HR 3.12 (1.60, 6.08)], coronary heart disease [HR 1.61 (1.13, 2.31)], stroke [HR 1.71 (1.07,2.72)], arrhythmia [HR 1.60 (1.13, 2.26)], cardiomyopathy [HR 1.71 (1.12, 2.61)], myocarditis [HR 6.11 (4.17,8.94)], hypertension [HR 1.70 (1.56, 1.85)], heart failure [HR 1.72 (1.15,2.59)] and cardiogenic shock [HR 2.09 (1.53,2.86)] compared to non-COVID-19 controls. Pooled risk differences in long COVID cases compared to controls were significantly higher for cardiomyopathy [0.15% (0.06, 0.23)], deep vein thrombosis [0.45% (0.06, 0.83)] and hypertension (0.32%, (0.06, 0.58) but not for thromboembolic disorders, coronary disease, stroke, arrhythmia, cardiomyopathy, myocarditis, hypertension, heart failure or cardiogenic shock.

CONCLUSION: The risk of cardiovascular disease increased significantly four weeks or more after recovering from acute COVID-19. Care for survivors after an acute attack of COVID-19 should include paying close attention to cardiovascular health and disease.

PROSPERO [CRD42022353965].}, } @article {pmid39944180, year = {2025}, author = {Bellone, S and Siegel, ER and Santin, AD}, title = {N-acetylcysteine (NAC) supplementation improves dyspnea and may normalize von Willebrand plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID.}, journal = {Gynecologic oncology reports}, volume = {57}, number = {}, pages = {101682}, pmid = {39944180}, issn = {2352-5789}, abstract = {OBJECTIVES: A subset of COVID-infected cancer patients may develop post-acute sequelae of COVID-19 (PASC), also known as Long COVID (LC). While LC is considered multifactorial in its pathogenesis, growing evidence suggests that persistent microvascular inflammation (ie, spike-induced endotheliosis) causing chronically elevated levels of clotting factors including von Willebrand factor (vWF), clumping/clotting of red blood cells and platelets, and thrombotic complications may be at the root of PASC/LC symptoms. N-Acetylcysteine (NAC), a precursor of glutathione, is an inexpensive FDA-approved drug/supplement endowed with mucolytic, antioxidant, anti-inflammatory and thrombolytic properties. Multiple reports have recently demonstrated the potential clinical activity of NAC in COVID-19 patients. We retrospectively evaluated responses to NAC supplementation in a total of 9 PASC/LC patients, 3 of which reporting regular use of NAC, followed in our Gynecologic Oncology clinic.

METHODS: Gynecologic patients using NAC supplement (3 patients) vs controls (6 patients) with persistent LC/PASC symptoms and with elevated plasmatic vWF levels were identified in our Gynecologic Oncology clinic database and evaluated for improvement/normalization in LC/PASC symptoms and vWF levels.

RESULTS: Subjective improvement in shortness of breath, brain fog and fatigue with normalization of vWF levels were noted in 3 out of 3 PASC/LC patients using oral NAC (600-1200 mg BID) vs none of the randomly selected cancer control patients with PASC/LC (Fisher's exact P = 0.0119).

CONCLUSIONS: These preliminary results suggest that NAC may represent an inexpensive, safe and potentially effective supplement to improve many PASC/LC-related symptoms. Prospective randomized studies with NAC in PASC/LC patients are needed to confirm these findings.}, } @article {pmid39944089, year = {2025}, author = {Vink, M and Vink-Niese, A}, title = {CBT and graded exercise therapy studies have proven that ME/CFS and long COVID are physical diseases, yet no one is aware of that.}, journal = {Frontiers in human neuroscience}, volume = {19}, number = {}, pages = {1495050}, pmid = {39944089}, issn = {1662-5161}, } @article {pmid39943820, year = {2025}, author = {Dieter, RS and Kempaiah, P and Dieter, EG and Alcazar, A and Tafur, A and Gerotziafas, G and Gonzalez Ochoa, A and Abdesselem, S and Biller, J and Kipshidze, N and Vandreden, P and Guerrini, M and Dieter, RA and Durvasula, R and Singh, M and Fareed, J}, title = {Cardiovascular Symposium on Perspectives in Long COVID.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {31}, number = {}, pages = {10760296251319963}, doi = {10.1177/10760296251319963}, pmid = {39943820}, issn = {1938-2723}, mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Cardiovascular Diseases/etiology ; Pandemics ; Congresses as Topic ; COVID-19 Drug Treatment ; }, abstract = {Significant progress has been made in treating Coronavirus disease (COVID) - an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An ominous turn in the pandemic is the evolving public health crisis emanating from persistent SARS-CoV-2 infection and its associated long-term impact. Long COVID or post-COVID syndrome describes protean symptoms that persist at least 3 months after the onset of acute illness and last for at least 2 months in individuals with a history of confirmed SARS-CoV-2 infection. Long COVID has become a public health concern. Millions of infected individuals are now facing chronic multi-organ failures, including neuropsychiatric, cardiovascular, pulmonary, and kidney complications. In general, the cause of long COVID syndrome is unclear but factors such as prolonged activation of immune responses, and viral persistence triggering transcription dysregulation of genes associated with normal thrombotic disease may play a role in cardiovascular complications. Although inflammatory biomarkers are reported in other disorders, it remains unclear whether similar biomarkers are associated with cardiovascular manifestations following COVID. Medications such as sulodexide directed at glycocalyx and coagulation have demonstrated benefits for long COVID in smaller studies. Here, we describe the outcomes of the symposium on the underlying cardiovascular mechanisms of the long COVID.}, } @article {pmid39942772, year = {2025}, author = {Kell, DB and Pretorius, E}, title = {The Proteome Content of Blood Clots Observed Under Different Conditions: Successful Role in Predicting Clot Amyloid(ogenicity).}, journal = {Molecules (Basel, Switzerland)}, volume = {30}, number = {3}, pages = {}, doi = {10.3390/molecules30030668}, pmid = {39942772}, issn = {1420-3049}, mesh = {Humans ; *Proteome/metabolism/analysis ; *Thrombosis/metabolism ; *Amyloid/metabolism ; *Blood Coagulation ; COVID-19/metabolism ; Sepsis/metabolism/blood ; SARS-CoV-2/metabolism ; }, abstract = {A recent analysis compared the proteome of (i) blood clots seen in two diseases-sepsis and long COVID-when blood was known to have clotted into an amyloid microclot form (as judged by staining with the fluorogenic amyloid stain thioflavin T) with (ii) that of those non-amyloid clots considered to have formed normally. Such fibrinaloid microclots are also relatively resistant to fibrinolysis. The proteins that the amyloid microclots contained differed markedly both from the soluble proteome of typical plasma and that of normal clots, and also between the diseases studied (an acute syndrome in the form of sepsis in an ITU and a chronic disease represented by Long COVID). Many proteins in the amyloid microclots were low in concentration in plasma and were effectively accumulated into the fibres, whereas many other abundant plasma proteins were excluded. The proteins found in the microclots associated with the diseases also tended to be themselves amyloidogenic. We here ask effectively the inverse question. This is: can the clot proteome tell us whether the clots associated with a particular disease contained proteins that are observed uniquely (or are highly over-represented) in known amyloid clots relative to normal clots, and thus were in fact amyloid in nature? The answer is in the affirmative in a variety of major coagulopathies, viz., venous thromboembolism, pulmonary embolism, deep vein thrombosis, various cardiac issues, and ischaemic stroke. Galectin-3-binding protein and thrombospondin-1 seem to be especially widely associated with amyloid-type clots, and the latter has indeed been shown to be incorporated into growing fibrin fibres. These may consequently provide useful biomarkers with a mechanistic basis.}, } @article {pmid39942487, year = {2025}, author = {Honorato-Cia, C and Cacho-Asenjo, E and Martinez-Simon, A and Aquerreta, I and Núñez-Córdoba, JM}, title = {Long COVID Research, 2020-2024: A PubMed-Based Bibliometric Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/healthcare13030298}, pmid = {39942487}, issn = {2227-9032}, support = {0011-3638-2020-000001 and 49-2022//Gobierno de Navarra/ ; }, abstract = {Long COVID is a SARS-CoV-2 infection-associated chronic condition with great potential to impact health and socioeconomic outcomes. The research efforts to face the challenges related to long COVID have resulted in a substantial amount of publications, which warrants the need for bibliometric profiling. This is a large-scale PubMed-based bibliometric analysis of more than 390,000 COVID-19 publications. The overall aim was to update the profile of long COVID publications in comparison with the rest of the COVID-19 scientific literature through December 2024. The estimated proportion of long COVID publications was relatively low (2.3% of all COVID-19 publications), although the cumulative frequency (n = 8928) continues to pose a challenge for proper information management. Currently, "treatment" and "mechanism" appear to be the most predominant research topics in the long COVID literature. Interestingly, this evaluation revealed a distinctive profile of the long COVID literature, with a clear preponderance of "case report" and "mechanism" research topics when compared with other COVID-19 publications. This evaluation also identified and ranked the most prolific scientific journals in the production of long COVID-related publications. This study may improve the visibility of long COVID research and contribute to the management of the growing scientific knowledge on long COVID.}, } @article {pmid39942451, year = {2025}, author = {Yang, Z and Tang, Y and Kong, L and Wang, X and Li, J and Hao, Y and Wang, Z and Gu, J}, title = {Self-Reported Long COVID and Its Impact on COVID-19-Related Worries and Behaviors After Lifting the COVID-19 Restrictions in China.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/healthcare13030262}, pmid = {39942451}, issn = {2227-9032}, support = {2023A03J0463//Guangzhou Science, Technology and Innovation Commission/ ; }, abstract = {OBJECTIVE: Since the lifting of the COVID-19 restrictions in China in November 2022, there has been a notable surge in the COVID-19 infection rate. Little is known about the prevalence of long COVID among the general adult population and its impact on COVID-19-related worries and behaviors after the policy change.

METHODS: This cross-sectional study recruited 1530 adults with prior COVID-19 infection in Guangzhou from February to March 2023. Logistic regression analyses and trend analyses were performed to investigate the associations between long COVID- and COVID-19-related worries and preventive behaviors.

RESULTS: The estimated prevalence of long COVID among adults in China was 18.0% (95% confidence interval: 16.1% to 20.0%). Common long COVID symptoms included cough (60.7%), fatigue (47.6%), dyspnea (34.5%), palpitation (26.2%), and insomnia (25.1%). Adjusted for background variables, individuals with long COVID exhibited higher level of COVID-19-related worries compared to those who had fully recovered from the infection (reference: without long COVID; adjusted odds ratios ranged from 1.87 to 2.55, all p values < 0.001). Participants primarily expressed worries regarding the potential for COVID-19 reinfection, the impact of the pandemic on daily life, the increasing number of COVID-19 cases and deaths, and the capacity of the healthcare system. While long COVID did not statistically significantly affect their preventive behaviors.

CONCLUSIONS: Long COVID was prevalent among the general adult population in China after lifting the COVID-19 restrictions, and it had a significant impact on COVID-19-related worries. This study highlights the importance of monitoring the mental health of individuals with long COVID and developing targeted intervention strategies to improve their adherence to preventive measures.}, } @article {pmid39942417, year = {2025}, author = {de Brito, FAM and Laranjeira, C and Moroskoski, M and Salci, MA and Rossoni, SL and Baccon, WC and de Oliveira, RR and Marques, PG and de Freitas Góes, HL and Mello, FF and da Cruz Blaszczak, FRB and Vissoci, JRN and Puente Alcaraz, J and Facchini, LA and Carreira, L}, title = {Self-Reported Post-COVID Symptoms at 18 Months After Infection Among Adults in Southern Brazil: A Cross-Sectional Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, doi = {10.3390/healthcare13030228}, pmid = {39942417}, issn = {2227-9032}, support = {This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-grant number: 001/2023.//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; It was also supported by FCT-Fundação para a Ciência e a Tecnologia, I.P. (UIDB/05704/2020 and UIDP/05704/2020) and by the Scientific Employment Stimulus-Institutional Call - [https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 18 Octo//Fundação para a Ciência e Tecnologia/ ; }, abstract = {BACKGROUND/OBJECTIVES: Currently, there is a limited understanding of the long-term consequences following acute COVID-19, referred to as long COVID. This cross-sectional study aims to analyze the prevalence of persistent signs and symptoms of long COVID, 18 months after primary SARS-CoV-2 infection in adults in southern Brazil.

METHODS: Using two national databases (the digital registry of SARS-CoV-2 positive cases), 370 individuals living in the state of Paraná (Brazil) were recruited. Data were collected through telephone interviews conducted in 2021 and 2022.

RESULTS: The overall prevalence of long COVID was 66.2% among study participants. During the acute phase of infection, the most common symptom clusters included neurological symptoms (87.0%; n = 318), followed by respiratory (82.0%; n = 301), musculoskeletal (66.0%; n = 241), digestive (50.0%; n = 184), psychological (38.0%; n = 138), and endocrine symptoms (28.0%; n = 104). In the 18 month follow-up, the main persistent symptoms were memory loss (42.7%), fatigue (32.2%), anxiety (23.5%), dyspnea (19.7%), and hair loss (19.7%). The proportion of participants with long COVID was statistically higher in females (73.9%), those with a family income below two minimum wages (94.7%), those who do not practice physical activity (83.3%), those who report poor sleep quality (93.3%), those who use long-term medication (85.9%), those who needed health care in the previous six months (87.3%), those who required professional and/or family care (79.3%), those who were in the ICU (79.0%), and those who used ventilatory support (77.5%).

CONCLUSIONS: Long COVID is a complex condition that requires long-term monitoring and investment in health services due to its high prevalence and the health consequences in the population.}, } @article {pmid39941627, year = {2025}, author = {Kapusta, J and Sinnadurai, S and Babicki, M and Kałuzińska-Kołat, Ż and Meijers, WC and Kołat, D and Manintveld, OC and Jankowski, P and Chudzik, M}, title = {Predictors of Cardiovascular Symptoms Among Long COVID Patients: Data from the Polish Long COVID Cardiovascular (PoLoCOV-CVD) Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/jcm14030956}, pmid = {39941627}, issn = {2077-0383}, abstract = {Background and aims: Long COVID symptoms persist globally, with a notable rise in cardiovascular disease (CVD) among COVID-19 survivors, including those without prior risk factors or hospitalizations. This study aims to identify predictors of cardiovascular-related Long COVID symptoms. Methods: This study included subjects with post-SARS-CoV-2 infections, categorizing them into three groups: non-Long COVID (non-LC), Long COVID (LC), and Long COVID with cardiovascular symptoms (cardio-LC) as part of the Polish Long COVID Cardiovascular (PoLoCOV-CVD) study collected between the years 2020 and 2022, comprising 4000 participants. Chi-square tests and logistic regression were used to report the prevalence and determinants of quality of life in cardio-LC, based on patient self-reported data including comorbidities and medications. Results: Of the 704 patients analyzed, 71.9% were female with a median age of 54 years (IQR: 45-64). Cardio-LC patients had statistically significant differences relative to the non-LC group in terms of blood pressure, elevated LDL cholesterol (p = 0.010), and non-HDL cholesterol (p = 0.013). In addition, cardio-LC patients were more likely to be female (p < 0.001) who exhibited psychological conditions, such as sleep disturbances (p < 0.001), anxiety (p < 0.001), and depression (p < 0.001) compared to the non-LC group. However, the multivariable logistic regression analysis revealed that only the female gender and sleep disturbances remained an independent predictor associated with cardio-LC (OR: 1.66, CI 1.12-2.46; OR: 1.742, CI 1.12-2.70) compared to participants without Long COVID. Conclusions: The significant positive association of female gender and sleep disturbances with cardiovascular complications during Long COVID highlights critical demographic and psychological factors that deserve attention in clinical practice.}, } @article {pmid39941487, year = {2025}, author = {Masuda, Y and Otsuka, Y and Tokumasu, K and Honda, H and Sakurada, Y and Matsuda, Y and Nakano, Y and Takase, R and Omura, D and Hasegawa, T and Ueda, K and Otsuka, F}, title = {Interrelationships Between Plasma Levels of Brain Natriuretic Peptide and Prolonged Symptoms Due to Long COVID.}, journal = {Journal of clinical medicine}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/jcm14030817}, pmid = {39941487}, issn = {2077-0383}, support = {23fk0108585h0001//Japan Agency for Medical Research and Development/ ; 2024//Japanese Society of Hospital General Medicine/ ; }, abstract = {Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, ≤18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment.}, } @article {pmid39941459, year = {2025}, author = {Muys, M and Demulder, A and Besse-Hammer, T and Ghorra, N and Rozen, L}, title = {Exploring Hypercoagulability in Post-COVID Syndrome (PCS): An Attempt at Unraveling the Endothelial Dysfunction.}, journal = {Journal of clinical medicine}, volume = {14}, number = {3}, pages = {}, doi = {10.3390/jcm14030789}, pmid = {39941459}, issn = {2077-0383}, support = {Not applicable//Centre Hospitalier Universitaire Brugmann/ ; }, abstract = {Background: The lingering effects of SARS-CoV-2 infection, collectively known as post-COVID syndrome (PCS), affect a significant proportion of recovered patients, manifesting as persistent symptoms like fatigue, cognitive dysfunction, and exercise intolerance. Increasing evidence suggests that endothelial dysfunction and coagulation abnormalities play a central role in PCS pathophysiology. This study investigates hypercoagulability and endothelial dysfunction in PCS through thrombin generation and the von Willebrand factor (VWF)/ADAMTS13 axis. Methods: Plasma samples from 97 PCS patients recruited since October 2020 by the clinical research unit of the Brugmann University Hospital were analyzed. A thrombin generation test was performed on a St-Genesia[®] analyzer (Stago) using the Thromboscreen kit; VWF antigen was determined on a CS-2500 analyzer (Siemens); and ADAMTS-13 activity was determined using an ELISA kit (Technozym[®]) on an ElX808 plate reader. Results: Thrombin generation testing revealed elevated thrombin production in PCS patients, particularly when thrombomodulin was included. Although most PCS patients showed normalized VWF/ADAMTS13 ratios, 11.3% exhibited elevated ratios (≥1.5), associated with advanced age. Conclusions: Patients with PCS show a consistent pattern of prolonged thrombo-inflammatory dysregulation, highlighted by elevated in vitro thrombin generation and the persistence of abnormal VWF/ADAMTS-13 ratios in a subset of patients.}, } @article {pmid39940991, year = {2025}, author = {Marzetti, E and Coelho-Júnior, HJ and Calvani, R and Girolimetti, G and Di Corato, R and Ciciarello, F and Galluzzo, V and Di Mario, C and Tolusso, B and Santoro, L and Giampaoli, O and Tomassini, A and Aureli, W and Tosato, M and Landi, F and Bucci, C and Guerra, F and Picca, A}, title = {Mitochondria-Derived Vesicles and Inflammatory Profiles of Adults with Long COVID Supplemented with Red Beetroot Juice: Secondary Analysis of a Randomized Controlled Trial.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, doi = {10.3390/ijms26031224}, pmid = {39940991}, issn = {1422-0067}, support = {D1.2023//Università Cattolica del Sacro Cuore/ ; 2024//Università Cattolica del Sacro Cuore/ ; 2022YNENP3//Ministero dell'università e della ricerca/ ; N/A//Centro Studi Achille e Linda Lorenzon/ ; Ricerca Corrente 2024//Ministero della Salute/ ; Progetto della rete degli IRCCS Aging R.C.R. 2022//Ministero della Salute/ ; IG 2021 - ID. 25795//Italian Association for Cancer Research/ ; DM 1557 11.10.2022//European Commission/ ; }, mesh = {Humans ; Female ; *Beta vulgaris/chemistry ; Male ; *Fruit and Vegetable Juices/analysis ; Adult ; Middle Aged ; *DNA, Mitochondrial/blood ; *Mitochondria/metabolism/drug effects ; *Extracellular Vesicles/metabolism/chemistry ; *Inflammation ; *COVID-19/immunology ; *Dietary Supplements ; SARS-CoV-2/drug effects ; Biomarkers/blood ; Interleukin-1beta/blood ; }, abstract = {In a recent clinical trial, beetroot juice supplementation for 14 days yielded positive effects on systemic inflammation in adults with long COVID. Here, we explored the relationship between circulating markers of mitochondrial quality and inflammation in adults with long COVID as well as the impact of beetroot administration on those markers. We conducted secondary analyses of a placebo-controlled randomized clinical trial testing beetroot juice supplementation as a remedy against long COVID. Analyses were conducted in 25 participants, 10 assigned to placebo (mean age: 40.2 ± 11.5 years, 60% women) and 15 allocated to beetroot juice (mean age: 38.3 ± 7.7 years, 53.3% women). Extracellular vesicles were purified from serum by ultracentrifugation and assayed for components of the electron transport chain and mitochondrial DNA (mtDNA) by Western blot and droplet digital polymerase chain reaction (ddPCR), respectively. Inflammatory markers and circulating cell-free mtDNA were quantified in serum through a multiplex immunoassay and ddPCR, respectively. Beetroot juice administration for 14 days decreased serum levels of interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha, with no effects on circulating markers of mitochondrial quality control. Significant negative associations were observed between vesicular markers of mitochondrial quality control and the performance on the 6 min walk test and flow-mediated dilation irrespective of group allocation. These findings suggest that an amelioration of mitochondrial quality, possibly mediated by mitochondria-derived vesicle recycling, may be among the mechanisms supporting improvements in physical performance and endothelial function during the resolution of long COVID.}, } @article {pmid39940787, year = {2025}, author = {Olivares-Martínez, E and Hernández-Ramírez, DF and Núñez-Álvarez, CA and Meza-Sánchez, DE and Chapa, M and Méndez-Flores, S and Priego-Ranero, Á and Azamar-Llamas, D and Olvera-Prado, H and Rivas-Redonda, KI and Ochoa-Hein, E and López-Mosqueda, LG and Rojas-Castañeda, E and Urbina-Terán, S and Septién-Stute, L and Hernández-Gilsoul, T and Aguilar-León, D and Torres-Villalobos, G and Furuzawa-Carballeda, J}, title = {Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, doi = {10.3390/ijms26031018}, pmid = {39940787}, issn = {1422-0067}, mesh = {Humans ; *STAT1 Transcription Factor/metabolism ; *COVID-19/metabolism/virology ; Phosphorylation ; *Receptors, Immunologic/metabolism ; *Monocytes/metabolism ; *SARS-CoV-2/metabolism ; *Collagen Type I/metabolism ; *Down-Regulation ; Male ; Female ; THP-1 Cells ; Middle Aged ; Macrophages/metabolism ; Cytokines/metabolism ; Adult ; COVID-19 Drug Treatment ; }, abstract = {The intramuscular administration of polymerized type I collagen (PTIC) for adult symptomatic COVID-19 outpatients downregulated hyperinflammation and improved symptoms. We inferred that LAIR1 is a potential receptor for PTIC. Thus, a binding assay and surface plasmon resonance binding assay were performed to estimate the affinity of the interaction between LAIR1 and PTIC. M1 macrophages derived from THP-1 cells were cultured with 2-10% PTIC for 24 h. Lysates from PTIC-treated THP-1 cells, macrophage-like cells (MLCs), M1, M1 + IFN-γ, and M1 + LPS were analyzed by Western blot for NF-κB (p65), p38, STAT1, and pSTAT1 (tyrosine[701]). Serum cytokine levels and monocyte LAIR1 expressions (Mo1 and Mo2) were analyzed by luminometry and flow cytometry in symptomatic COVID-19 outpatients on PTIC treatment. PTIC-bound LAIR1 had a similar affinity to collagen in M1 macrophages. It downregulated pSTAT1 in IFN-γ-induced M1. COVID-19 patients under PTIC treatment showed a significant decrease in Mo1 percentages and cytokines (IP-10/MIF/eotaxin/IL-8/IL-1RA/M-CSF) associated with STAT1 and an increase in the Mo2 subset. The inflammatory mediators and Mo1 downregulation were related to better oxygen saturation and decreased dyspnea, chest pain, cough, and chronic fatigue syndrome in the acute and long-term phase of infection. PTIC is an agonist of LAIR1 and downregulates STAT-1 phosphorylation. PTIC could be relevant for treating STAT1-mediated inflammatory diseases, including COVID-19 and long COVID.}, } @article {pmid39940333, year = {2025}, author = {Dorczok, MC and Mittmann, G and Mossaheb, N and Schrank, B and Bartova, L and Neumann, M and Steiner-Hofbauer, V}, title = {Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systematic Review.}, journal = {Nutrients}, volume = {17}, number = {3}, pages = {}, doi = {10.3390/nu17030475}, pmid = {39940333}, issn = {2072-6643}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diet therapy/therapy ; *Dietary Supplements ; Fatigue ; Female ; Selenium/administration & dosage ; Carnitine/administration & dosage ; Treatment Outcome ; Ubiquinone/analogs & derivatives/administration & dosage ; Adult ; Male ; }, abstract = {Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmunological disorder with limited treatment options. Despite the widespread use of Dietary Supplements (DSs) among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. This systematic review aims to provide an updated synthesis of the efficacy of DS interventions and explore possible mechanisms underlying their therapeutic effects. Methods: This systematic review was conducted according to PRISMA guidelines. Several databases (Ebsco Host, PubMed, Scopus, Google Scholar) were used for the systematic search, which was based on the broad search terms ME/CFS and DS with a focus on publications between 1994 and 2024. The primary outcome was fatigue, with additional considerations including psychological well-being, physical activity, and biochemical markers. Two independent researchers screened the studies for eligibility in a multi-stage process and assessed quality and bias using Cochrane's risk of bias tools (RoB-2, ROBINS-I). Results: Fourteen studies (N = 809) of heterogeneous designs were included, showing a high risk of bias, mostly due to missing data and selection bias. While some interventions (L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10-selenium combination, NADH and NADH-CoQ10 combination) showed significant reductions in fatigue, methodological limitations, like small sample sizes and missing data, prevent firm conclusions. Mixed results were reported for secondary outcomes like cognitive function and inflammatory markers. Six studies noted adverse effects, including nausea and insomnia. Conclusions: Though some DSs showed potential in reducing fatigue in ME/CFS, methodological limitations and inconsistent results hinder definitive conclusions. Future research should improve diagnostic criteria and include more diverse populations.}, } @article {pmid39939334, year = {2025}, author = {Rodriguez-Torres, JF and Romero-Ibarguengoitia, ME and Garza-Silva, A and Rivera-Cavazos, A and Hurtado-Cabrera, M and Kalife-Assad, R and Villarreal-Parra, DL and Loose-Esparza, A and Gutierrez-Arias, JJ and Mata-Porras, YG and Ojeda-Salazar, DA and Morales-Rodriguez, DP and Sanz-Sánchez, MÁ and Gonzalez-Cantú, A}, title = {Association between Mexican vaccination schemes and the duration of long COVID syndrome symptoms.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {5301}, pmid = {39939334}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; Mexico/epidemiology ; *COVID-19/epidemiology/prevention & control ; Middle Aged ; Adult ; Cross-Sectional Studies ; *Vaccination ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/isolation & purification ; *COVID-19 Vaccines/administration & dosage ; Comorbidity ; Prevalence ; Risk Factors ; }, abstract = {The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to gauge the prevalence of Long COVID syndrome in northeastern Mexico, correlating it with patients' comorbidities and vaccination records. We carried out an observational cross-sectional approach, by administering a comprehensive questionnaire covering patients' medical history, demographics, vaccination status, COVID-related symptoms, their duration, and any treatment received. Our participant cohort included 804 patients, averaging 41.5 (SD 13.6) years in age, with 59.3% being women. Notably, 168 individuals (20.9%) met Long COVID criteria. Our analysis of COVID-19 long lasting compared vaccination schemes, unveiling a significant difference between vaccinated and unvaccinated groups (p = < 0.001). Through linear regression model, we found male gender (β = - 0.588, p < 0.001) and vaccination status (β = 0.221, p = 0.015) acted as protective factors against Long COVID symptom duration, while higher BMI was a risk factor (β = - 0.131, p = 0.026). We saw that the duration of Long COVID was different within vaccinated patients, and we did not find any association of comorbidities with an increase in the presence of symptoms. Even three years after the pandemic, a significant prevalence of Long COVID persists, and there is still a lack of standardized information and any possible treatment regarding this condition.}, } @article {pmid39938278, year = {2025}, author = {Motta, M and Callaghan, T and Padmanabhan, M and Ross, JC and Gargano, LM and Bowman, S and Yokum, D}, title = {Identifying and mitigating the public health consequences of meta-ignorance about "Long COVID" risks.}, journal = {Public health}, volume = {241}, number = {}, pages = {19-23}, doi = {10.1016/j.puhe.2025.02.003}, pmid = {39938278}, issn = {1476-5616}, abstract = {OBJECTIVES: While past work studies public concern about "Long COVID," fewer have asked what the public knows and/or purports to know about Long COVID. This is an important oversight, as low knowledge and/or "meta-ignorance" (Dunning Kruger Effect; DKE) concerning Long COVID might undermine public willingness to take action to protect themselves and others from endemic COVID-19.

STUDY DESIGN: In a nationally representative survey of US adults, we measure the correspondence between Americans' objective and perceived Long COVID knowledge.

METHODS: We estimate a series of multivariate regression models that assess (a) the socio-demographic correlates and (b) public health consequences of Long COVID meta-ignorance.

RESULTS: We detect prevalent meta-ignorance about Long COVID. Greater than one fifth of Americans express high confidence in their perceived Long COVID knowledge, despite exhibiting lower than average objective knowledge. The expression of DKE is associated with a series of deleterious public health and health policy outcomes, including: opposition to workplace COVID-19 vaccine mandates, annual COVID-19 vaccine hesitancy, and an increased likelihood of being sick with Long COVID.

CONCLUSION: Our work provides novel insights into the promises and potential limitations of health communication efforts to provide the public with basic facts about the causes and consequences of Long COVID.}, } @article {pmid39285063, year = {2025}, author = {Ehm, F and Tesch, F and Menzer, S and Loser, F and Bechmann, L and Vivirito, A and Wende, D and Batram, M and Buschmann, T and Ludwig, M and Roessler, M and Seifert, M and Sarganas Margolis, G and Reitzle, L and Koenig, C and Schulte, C and Ballesteros, P and Bassler, S and Bitterer, T and Riederer, C and Berner, R and Scheidt-Nave, C and Schmitt, J and Toepfner, N}, title = {Long/post-COVID in children and adolescents: symptom onset and recovery after one year based on healthcare records in Germany.}, journal = {Infection}, volume = {53}, number = {1}, pages = {415-426}, pmid = {39285063}, issn = {1439-0973}, support = {2521NIK705//Bundesministerium für Gesundheit/ ; }, mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; Adolescent ; Germany/epidemiology ; Child ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Infant ; *SARS-CoV-2 ; Infant, Newborn ; *Post-Acute COVID-19 Syndrome ; Incidence ; }, abstract = {PURPOSE: Evidence on the incidence and persistence of post-acute sequelae of COVID-19 (PASC) among children and adolescents is still limited.

METHODS: In this retrospective cohort study, 59,339 children and adolescents with laboratory-confirmed COVID-19 in 2020 and 170,940 matched controls were followed until 2021-09-30 using German routine healthcare data. Incidence rate differences (ΔIR) and ratios (IRR) of 96 potential PASC were estimated using Poisson regression. Analyses were stratified according to age (0-11, 12-17 years), and sex. At the individual level, persistence of diagnoses in patients with onset symptoms was tracked starting from the first quarter post-infection.

RESULTS: At 0-3 month follow-up, children and adolescents with a previous SARS-CoV-2 infection showed a 34% increased risk of adverse health outcome, and approximately 6% suffered from PASC in association with COVID-19. The attributable risk was higher among adolescents (≥ 12 years) than among children. For most common symptoms, IRRs largely persisted at 9-12 month follow-up. IRR were highest for rare conditions strongly associated with COVID-19, particularly inflammatory conditions among children 0-11 years, and chronic fatigue and respiratory insufficiency among adolescents. Tracking of diagnoses at the individual level revealed similar rates in the decline of symptoms among COVID-19 and control cohorts, generally leaving less than 10% of the patients with persistent diagnoses after 12 months.

CONCLUSION: Although very few patients presented symptoms for longer than 12 months, excess morbidity among children and, particularly, adolescents with a history of COVID-19 means a relevant burden for pediatric care.}, } @article {pmid39934846, year = {2025}, author = {Salzmann, S and de Vroege, L and Engelmann, P and Fink, P and Fischer, S and Frisch, S and Gormsen, LK and Hüfner, K and Kop, WJ and Köteles, F and Lehnen, N and Löwe, B and Pieh, C and Pitron, V and Rask, CU and Sainio, M and Schaefert, R and Shedden-Mora, M and Toussaint, A and von Känel, R and Werneke, U and Rief, W and , }, title = {Assessment of psychosocial aspects in adults in post-COVID-19 condition: the EURONET-SOMA recommendations on core outcome domains for clinical and research use.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {81}, pmid = {39934846}, issn = {1741-7015}, mesh = {Humans ; *COVID-19/psychology ; Adult ; SARS-CoV-2 ; Outcome Assessment, Health Care ; Europe ; Post-Acute COVID-19 Syndrome ; Consensus ; }, abstract = {BACKGROUND: Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.

METHODS: In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.

RESULTS: We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, "outcomes", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain "mechanisms" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, "risk factors", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.

CONCLUSIONS: The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.}, } @article {pmid39934662, year = {2025}, author = {Assis, GMCC and Veiga, IGD and Reis, RNR and Menezes, DC and Xavier, SS and Chaves, ECR and Sousa, JR and Quaresma, JAS and Falcão, LFM and Lima, PDL}, title = {Investigation of renal function in patients with long COVID in the Amazon region: a cross-sectional study.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {202}, pmid = {39934662}, issn = {1471-2334}, support = {13/2020'//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)/ ; #006/2020//Amazon Foundation for Research Support (FAPESPA)/ ; #09/2021//Secretary of Science, Technology, and Higher, Professional, and Technological Education (SECTET)/ ; INCT:406360/2022-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico-Brazil/ ; }, mesh = {Humans ; *COVID-19/physiopathology/epidemiology/complications ; Cross-Sectional Studies ; Male ; Middle Aged ; Female ; Aged ; Brazil/epidemiology ; Kidney/physiopathology ; SARS-CoV-2 ; Adult ; Kidney Function Tests ; Aged, 80 and over ; }, abstract = {BACKGROUND: COVID-19 became a pandemic disease in 2020, with multisystem involvement and high renal morbidity during the acute phase. Some affected patients began to present new or persistent symptoms in a condition known as Long COVID. The study aimed to evaluate renal function using clinical and laboratory findings, and to establish the frequency and staging of renal function decline in Long COVID patients, as well as the associated factors.

METHODS: This is a cross-sectional observational study that selected participants from a Long COVID clinical care program between 2020 and 2022.

RESULTS: A total of 246 patients were selected for this study, and renal function decline was found in 83 (33.7%). Patients over 60 years (29.6%) and those who developed glycaemic alterations (41.8%) exhibited a higher prevalence of renal outcomes in long COVID. Some laboratory test as LDH levels and glycated hemoglobin seems to have a statistic relation with a decrease in renal function (p < 0.05).

CONCLUSION: A decline in renal function was common in patients with Long COVID in this study, and older age and glycaemic alterations were relevant to this condition. Some laboratory markers can be used to predict this outcome.}, } @article {pmid39934118, year = {2025}, author = {Ranque, B and Garner, P and Allenbach, Y and Hupin, D and David, AS and Wade, D and Sharpe, M and Garcin, B and Little, P and Tinazzi, M and Fink, P and Hamilton, W and Peto, T and Lemogne, C and Wyller, VBB and Chalder, T and Coebergh, J}, title = {Reply: Muscle abnormalities in Long COVID.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1490}, pmid = {39934118}, issn = {2041-1723}, } @article {pmid39934110, year = {2025}, author = {Appelman, B and Charlton, BT and Goulding, RP and Kerkhoff, TJ and Breedveld, EA and Noort, W and Offringa, C and Bloemers, FW and van Weeghel, M and Schomakers, BV and Coelho, P and Posthuma, JJ and Aronica, E and Wiersinga, WJ and van Vugt, M and Wüst, RCI}, title = {Reply: Muscle abnormalities in Long COVID.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1491}, pmid = {39934110}, issn = {2041-1723}, } @article {pmid39933578, year = {2025}, author = {Barado, E and Carlos, S and Moreno-Galarraga, L and Amer, F and Escrivá, N and Torres, MG and Reina, G and Fernandez-Montero, A}, title = {Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Long COVID: A Retrospective Case-Control Study.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13908}, pmid = {39933578}, issn = {1365-2567}, abstract = {Long COVID is an emerging condition with an important impact on the quality of life of affected individuals. This study aims to analyse the association between complete vaccination prior to SARS-CoV-2 infection and the subsequent development of long COVID, including its symptoms and their frequency through a retrospective case-control study. Cases included participants with long COVID, while controls were participants without long COVID but who had a SARS-CoV-2 infection. Data were collected through a self-reported survey. The study demonstrates a significant association between vaccination and a lower incidence of long COVID, adjusted for sex, age, university education, body mass index, physical activity, race, tobacco use, alcohol intake, adherence to Mediterranean diet, previous illness, flu vaccination, health care worker, high-risk COVID worker and sleep hours and sedentarism (OR 0.49, CI 95% 0.28-0.87). Furthermore, there is a statistically significant association between vaccination and reduced symptoms such as anosmia, dysgeusia, myalgia or arthralgia, as well as a lower overall number, adjusted for the aforementioned variables. These findings suggest that the vaccine could be associated not only to a milder course of SARS-CoV-2 infection but also with an improvement in the state of long COVID and its symptoms.}, } @article {pmid39932650, year = {2025}, author = {di Filippo, L and Doga, M and Mangini, F and Gifuni, L and Sahagun, SJ and Rovere Querini, P and Rosen, CJ and Giustina, A}, title = {Morphometric vertebral fractures at hospitalization associate with Long COVID occurrence.}, journal = {Journal of endocrinological investigation}, volume = {}, number = {}, pages = {}, pmid = {39932650}, issn = {1720-8386}, abstract = {PURPOSE: Long COVID is a multisystemic syndrome leading to significant morbidity. To date, a comprehensive characterization of underlying risk factors is still being defined. Osteoporosis and vertebral fractures (VFs) were associated with worse acute COVID-19 and impaired respiratory recovery after hospitalization. Therefore, we aimed to assess the potential relationship between VFs and the occurrence of the Long COVID syndrome.

METHODS: Patients hospitalized for acute COVID-19 and subsequently seen in our outpatient follow-up clinic 6-months after discharge were evaluated. We retrospectively included patients with available lateral chest X-rays performed at admission suitable for VFs assessments. We excluded patients with active neoplasia, and those managed at home or those hospitalized in ICU. Long COVID was diagnosed with a multidisciplinary evaluation.

RESULTS: One-hundred sixty-two patients were included in the study. At least one VF was found in 42 patients at presentation (25.9%). Patients with VFs were significantly older and predominantly males. Long COVID was diagnosed in 25 patients (15.4%). No differences were found between patients with and without Long COVID regarding demographics and comorbidities; however, those with Long COVID were characterized by a higher prevalence of VFs at time of hospitalization for acute COVID-19 (48% vs. 22%, p = 0.01). After matching patients with and without VFs in a 1:1 ratio for demographics, comorbidities, and COVID-19 severity, a total of 84 patients were analysed and those presenting VFs were characterized by a significant higher prevalence of Long COVID (28.6% vs. 9.5%, p = 0.04) and VFs resulted as the only significant independent risk factor for Long COVID occurrence.

CONCLUSIONS: We observed that prevalent VFs detected at hospital admission were distinctive clinical features of patients presenting with Long COVID 6-months after discharge, independently from acute disease severity and other confounding factors. This highlights a potential detrimental association between skeletal fragility and the development of Long COVID.}, } @article {pmid39930426, year = {2025}, author = {DeVoss, R and Carlton, EJ and Jolley, SE and Perraillon, MC}, title = {Healthcare utilization patterns before and after a long COVID diagnosis: a case-control study.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {514}, pmid = {39930426}, issn = {1471-2458}, support = {P30CA046934/NH/NIH HHS/United States ; P30CA046934/NH/NIH HHS/United States ; P30CA046934/NH/NIH HHS/United States ; 1U18HS029943-01//Agency for Healthcare Research and Quality/ ; }, mesh = {Humans ; Female ; Male ; Case-Control Studies ; Middle Aged ; Colorado/epidemiology ; *COVID-19/epidemiology/diagnosis ; *Patient Acceptance of Health Care/statistics & numerical data ; Retrospective Studies ; Aged ; Adult ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Hospitalization/statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND: Documenting Long COVID cases has been challenging partly due to the lack of population-level data and uncertain diagnostic criteria, hindering the ability to ascertain healthcare utilization patterns over time. The objective of this study is to examine the characteristics and healthcare utilization patterns of Long COVID patients in Colorado pre- and post-diagnosis compared to controls.

METHODS: Retrospective, longitudinal case-control study using a 100% sample of Colorado's All-Payer Claims Database. The sample includes individuals 18 or older diagnosed with Long COVID between October 1, 2021, and August 1, 2022, with patients followed until August 2023. Long COVID was identified using the International Classification of Diseases, 10th Revision, U09.9 code in medical insurance claims. Analysis of healthcare utilization required one year of continuous enrollment before and after diagnosis. Controls were matched 2:1 on age group, sex, payer, and index month to account for contemporaneous trends in utilization.

RESULTS: 26,358 individuals were ever diagnosed with Long COVID, resulting in a claims-based prevalence of 674 per 100,000 during the study period (population 3,906,402 individuals). Of these, 12,698 individuals had continuous enrollment and a Long COVID diagnosis: mean (SD) age, 59.0 (17.1); 65.3% female; 60.1% white; 83.0% residing in urban areas. The Long COVID sample was matched with 25,376 controls. Before diagnosis, 17% of Long COVID patients were hospitalized at least once, and 40% visited an emergency department on at least one occasion. Within the year following diagnosis, utilization of acute healthcare services significantly decreased relative to controls: hospitalizations, -6.1percentage points (p.p.), emergency department visits, -7.7 p.p., whereas outpatient services and medications increased: office visits, 3.6 p.p.; specialist office visits, 4.7 p.p.; and 5.2 new medications, (controls: 2.8). Changes in diagnoses of some conditions (e.g., metastatic carcinomas and lung cancer) were similar between groups.

CONCLUSIONS AND RELEVANCE: Long COVID patients increased outpatient healthcare utilization following a diagnosis, switching from acute care settings. The change in service settings among this population suggests that diagnosis could lead to better patient management. Healthcare utilization among these patients is high, underscoring the need to understand the Long COVID burden on healthcare systems with population-level data.}, } @article {pmid39930413, year = {2025}, author = {Cordelli, E and Soda, P and Citter, S and Schiavon, E and Salvatore, C and Fazzini, D and Clementi, G and Cellina, M and Cozzi, A and Bortolotto, C and Preda, L and Francini, L and Tortora, M and Castiglioni, I and Papa, S and Sona, D and Alì, M}, title = {Correction: Machine learning predicts pulmonary long Covid sequelae using clinical data.}, journal = {BMC medical informatics and decision making}, volume = {25}, number = {1}, pages = {68}, doi = {10.1186/s12911-025-02918-8}, pmid = {39930413}, issn = {1472-6947}, } @article {pmid39929492, year = {2025}, author = {Pierce, CW and Raj, SR}, title = {Orthostatic hypotension and anemia.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {197}, number = {5}, pages = {E135}, doi = {10.1503/cmaj.151709-l}, pmid = {39929492}, issn = {1488-2329}, } @article {pmid39927297, year = {2025}, author = {Moritani, I and Yamanaka, K and Nakamura, T and Tanaka, J and Kainuma, K and Okamoto, M and Ieki, T and Wada, H and Shiraki, K}, title = {Prevalence of and risk factors for long COVID following infection with the COVID‑19 omicron variant.}, journal = {Medicine international}, volume = {5}, number = {2}, pages = {17}, pmid = {39927297}, issn = {2754-1304}, abstract = {The aim of the present study was to clarify the current status of persistent symptoms following omicron variants of COVID-19 [long COVID (LC)] and the risk factors associated with the development of LC. For this purpose, a cross-sectional survey of patients with COVID-19 treated at the authors' hospital and at four associated outpatient clinics was conducted. Questionnaires about a post-infection condition were sent by post to 3,399 patients. A comparison was made of patients infected when the omicron variant was prevalent (omicron group) and patients infected prior to that (pre-omicron group). Valid responses were received from 1,113 (32.7%) patients. The percentages of patients in whom some type of symptom or sequelae continued after 1, 3 and 6 months were 44, 37 and 28%, respectively, in the pre-omicron group, and 20, 12 and 9%, respectively, in the omicron group. The percentages were significantly lower in the omicron group. In the multivariate analysis of risk factors for LC at 3 months, significant risk factors were hospitalization [odds ratio (OR), 1.910; P<0.01] and old age (OR, 1.120; P<0.05). Conversely, the incidence of LC was lower with vaccination (OR, 0.830; P<0.01) and in the omicron group (OR, 0.490; P<0.01). In the omicron group, underlying disease (particularly emphysema, bronchial asthma, rheumatoid or collagen disease and hypertension) and hospitalization were significantly associated with LC (P<0.01). On the whole, the present study demonstrates that the incidence of LC was >10% even in the omicron group. Patients who required hospitalization and patients with underlying conditions require careful attention for the development of LC.}, } @article {pmid39925756, year = {2025}, author = {Alie, MS and Tesema, GA and Abebe, GF and Girma, D}, title = {The prolonged health sequelae "of the COVID-19 pandemic" in sub-Saharan Africa: a systematic review and meta-analysis.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1415427}, pmid = {39925756}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; Africa South of the Sahara/epidemiology ; *Quality of Life ; SARS-CoV-2 ; Survivors/statistics & numerical data ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Survivors of coronavirus disease 2019 (COVID-19) often face persistent and significant challenges that affect their physical, mental, and financial wellbeing, which can significantly diminish their overall quality of life. The emergence of new symptoms or the persistence of existing ones after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis has given rise to a complex clinical issue known as "long COVID-19" (LC). This situation has placed additional strain on global healthcare systems, underscoring the urgent need for ongoing clinical management of these patients. While numerous studies have been conducted on the long-term effects of COVID-19, our systematic review, and meta-analysis, is the first of its kind in sub-Saharan Africa, providing a comprehensive understanding of the situation in the region and highlighting the necessity for continuous clinical management.

OBJECTIVE: This study aimed to systematically synthesize evidence on the persistent sequelae of COVID-19 and their predictors in sub-Saharan Africa.

METHODS: A thorough search was conducted across multiple databases, including PubMed/MEDLINE, Web of Science, Google/Google Scholar, African online journals, and selected reference lists, from the inception of these databases until January 12, 2024. A meta-analysis of proportions was conducted using the random-effects restricted maximum-likelihood model. The association between various factors was also analyzed to determine the pooled factors that influence long COVID-19 outcomes.

RESULTS: Our comprehensive analysis of 16 research articles, involving a total of 18,104 participants revealed a pooled prevalence of COVID-19 sequelae at 42.1% (95% CI: 29.9-55.4). The long-term health sequelae identified in this review included persistent pulmonary sequelae (27.5%), sleep disturbance (22.5%), brain fog (27.4%), fatigue (17.4%), anxiety (22.3%), and chest pain (13.2%). We also found a significant association was observed between comorbidities and long COVID-19 sequelae [POR = 4.34 (95% CI: 1.28-14.72)], providing a comprehensive understanding of the factors influencing long COVID-19 outcomes.

CONCLUSION: COVID-19 can have long-lasting effects on various organ systems, even after a person has recovered from the infection. These effects can include brain fog, pulmonary symptoms, sleep disturbances, anxiety, fatigue, and other neurological, psychiatric, respiratory, cardiovascular, and general symptoms. It is crucial for individuals who have recovered from COVID-19 to receive careful follow-up care to assess and reduce any potential organ damage and maintain their quality of life.

Clinicaltrial.gov, identifier CRD42024501158.}, } @article {pmid39922599, year = {2025}, author = {}, title = {Correction: Defining and measuring long COVID fatigue: a scoping review.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e088530corr1}, doi = {10.1136/bmjopen-2024-088530corr1}, pmid = {39922599}, issn = {2044-6055}, } @article {pmid39921694, year = {2025}, author = {Hattori, F and Nishiyama, J and Hasuo, H}, title = {Correlation of Interferons and Autoimmune Aspects in Long COVID-19 Patients.}, journal = {International immunology}, volume = {}, number = {}, pages = {}, doi = {10.1093/intimm/dxaf008}, pmid = {39921694}, issn = {1460-2377}, abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a major global health challenge, with its underlying mechanisms remaining poorly understood despite substantial research and clinical trials. This study investigates the role of the interferon (IFN) axis in the pathogenesis of PASC, drawing parallels to systemic lupus erythematosus (SLE). The potential pathogenic role of IFNs was detected by meta-analyses of mRNA sequencing data comparing PASC patients to healthy controls. We analyzed serum samples from 39 PASC patients and found significant correlations among multiple IFN subtypes, including IFN alpha-2, beta, gamma, lambda-1, and lambda-2/3. The biological activity of IFNs in the serum was positively correlated with levels of both total and type III IFNs. Notably, we detected the widespread presence of anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies in these patients, with anti-dsDNA levels showing a strong correlation with IFN activity. Based on these findings, we propose a hypothetical autoimmune pathogenesis for PASC highlighting the crucial role of IFN signaling.}, } @article {pmid39921187, year = {2025}, author = {Pouliopoulou, DV and Hawthorne, M and MacDermid, JC and Billias, N and Miller, E and Quinn, K and Décary, S and Razak, FA and Cheung, A and Galiatsatos, P and Pereira, TV and Bobos, P}, title = {Prevalence and Impact of Post-Exertional Malaise on Recovery in Adults with Post COVID-19 Condition. A Systematic Review with Meta-Analysis.}, journal = {Archives of physical medicine and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.apmr.2025.01.471}, pmid = {39921187}, issn = {1532-821X}, abstract = {OBJECTIVE: To assess the prevalence of PEM in people with PCC; and the change in prevalence of PEM following rehabilitation interventions in people with PCC.

DATA SOURCES: We searched MEDLINE, Embase, Central, CINAHL, PsychINFO and Clinical Trial Registries from inception until January 12[th], 2024.

STUDY SELECTION: We included observational studies that measured the prevalence of PEM in adults with PCC and interventional studies that measured the change in prevalence of PEM following rehabilitation interventions in adults with PCC. Two independent researchers screened titles and abstracts. Any discrepancies underwent full text review. Two independent researchers screened the articles included at the full text level. Any discrepancies were resolved by consensus.

DATA EXTRACTION: Two independent researchers extracted data from eligible studies. We extracted point-prevalence from the cross-sectional studies; and period-prevalence from the longitudinal studies. Two independent reviewers assessed the risk of bias (ROB). Discrepancies were resolved with a senior research team member. For the prevalence studies we used the Cochrane Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool. For randomised controlled trials we used the Cochrane Risk of Bias tool II - (RoB2). For non-randomised interventional studies we used the Cochrane Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I)[1] to assess the non-randomised studies. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to grade the quality of the evidence DATA SYNTHESIS: We performed a single-arm proportional meta-analysis to synthesize prevalence estimates using logit transformation. We conducted a sensitivity analysis using multilevel-mixed-effects logistic regression. This study is registered with PROSPERO (CRD42024516682).The prevalence of PEM in community-dwelling adults living with PCC was 36% (95% CI: 0.19 to 0.57; 2,263 participants). Two of the included studies (61 patients) found a decrease in the frequency and intensity of PEM episodes in adults with PCC following a tailored rehabilitation program centered on integrating pacing approaches. None of the included studies reported an increase of PEM symptoms' frequency and intensity following an individually tailored rehabilitation program with a therapeutic exercise component (5 studies; 892 patients).

CONCLUSIONS: Our research confirms that there is a large burden of PEM in adults living with PCC, highlighting a critical challenge for healthcare systems and an urgent need for more inclusive and rigorous research, to offer safe and effective therapeutic solutions and meet the variable needs of people with PCC that experience PEM.There is a subgroup of patients with PCC that do not experience PEM; and there is limited evidence that supervised, individually tailored, symptom-titrated rehabilitation interventions with active exercise components may not trigger PEM in this subgroup of people with PCC. Our results are limited by the insufficient reporting of the percentage of PEM in the baseline before enrolling patients in the rehabilitation programs, and the large number of studies using non-validated, unstandardized tools to measure PEM in people with PCC, hence there is an urgent need to strengthen the methods of future trials.}, } @article {pmid39920063, year = {2025}, author = {Zeraatkar, D and Ling, M and Kirsh, S and Jassal, T and Pitre, T and Chakraborty, S and Turner, T and Turkstra, L and McIntyre, RS and Izcovich, A and Mbuagbaw, L and Agoritsas, T and Flottorp, SA and Garner, P and Couban, RJ and Busse, JW}, title = {Interventions for the management of post-COVID-19 condition (long COVID): protocol for a living systematic review and network meta-analysis.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e086407}, doi = {10.1136/bmjopen-2024-086407}, pmid = {39920063}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/therapy/complications ; *Systematic Reviews as Topic ; *Network Meta-Analysis as Topic ; *SARS-CoV-2 ; Fatigue/etiology/therapy ; Research Design ; Post-Acute COVID-19 Syndrome ; Meta-Analysis as Topic ; Myalgia/etiology/therapy ; }, abstract = {BACKGROUND: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.

OBJECTIVE: To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.

METHODS: Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.

CONCLUSION: This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.

ETHICS AND DISSEMINATION: The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.}, } @article {pmid39920062, year = {2025}, author = {Hersche, R and Weise, A and Riggi, E and Di Tanna, GL and Barbero, M}, title = {Energy management education for persons living with long COVID-related fatigue (EMERGE): protocol of a two-parallel arms target trial emulation study in a multicentre outpatient intervention setting with an online control group register.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e098574}, doi = {10.1136/bmjopen-2024-098574}, pmid = {39920062}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/therapy ; *Fatigue/therapy/etiology ; *Quality of Life ; Self Efficacy ; Self-Management/methods ; SARS-CoV-2 ; Patient Education as Topic/methods ; Cost-Benefit Analysis ; Occupational Therapy/methods ; Multicenter Studies as Topic ; Prospective Studies ; }, abstract = {INTRODUCTION: Energy management education (EME) is a manualised, evidence-based self-management education programme developed and delivered by occupational therapists for persons living with chronic disease-related fatigue. Studies have shown that EME can positively affect self-efficacy, fatigue impact and quality of life in persons with chronic conditions, while data on persons with long COVID are lacking.The primary aim is to evaluate if adding EME to the standard care improves outcomes in persons with long COVID-related fatigue. The secondary aim is to explore the energy management behavioural strategies applied in daily routines and investigate the influencing factors of implementing behavioural changes. The third aim is to perform a cost-effectiveness analysis of EME.

METHODS AND ANALYSIS: Using observational data, we will emulate a prospective two-parallel arms target trial to assess whether adding EME to the standard care is associated with improved outcomes in patients with long COVID-related fatigue. The estimated sample size to detect a post-intervention difference of 1.5 points in self-efficacy to implement energy conservation strategies with 90% power (0.05 alpha) is 122 people (1:1 ratio).Persons with long COVID-related fatigue who follow EME as part of their standard care will be recruited and included in the experimental group (EG), while potential participants for the control group (CG) will be recruited from a register and prospectively matched to a participant in the EG by applying the propensity score technique. The 'standard of care' of the CG will include any intervention, except occupational therapy-based EME in peer groups. The causal contrast of interest will be the per-protocol effect. Four self-reported questionnaires (fatigue impact, self-efficacy in performing energy management strategies, competency in performing daily activities, health-related quality of life) will be administered at baseline (T0; week 0), after lesson 7 (T1; week 6), post-intervention (T2; week 14) and follow-up (T3, week 24). Our main assessment will be at T2. Disease-related and productivity cost data will be collected, and a cost-effectiveness profile of the EME intervention will be compared with standard care.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the competent Swiss ethics commission.Findings will be reported (1) to the study participants; (2) to patient organisations and hospitals supporting EMERGE; (3) to funding bodies; (4) to the national and international occupational therapy community and healthcare policy; (5) will be presented at local, national, and international conferences and (6) will be disseminated by peer-review publications.}, } @article {pmid39919323, year = {2024}, author = {Eftekhari, H and Pearce, G and Staniszewska, S and Seers, K}, title = {Understanding the experiences of people who have Postural Orthostatic Tachycardia Syndrome (POTS) and the health professionals who care for them: A grounded theory study.}, journal = {International journal of nursing studies}, volume = {164}, number = {}, pages = {104986}, doi = {10.1016/j.ijnurstu.2024.104986}, pmid = {39919323}, issn = {1873-491X}, abstract = {UNLABELLED: Understanding the experiences of people who have postural orthostatic tachycardia syndrome (POTS) and the health professionals who care for them: a grounded theory study.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an under recognised, predominantly female condition. Awareness of this condition has increased due its association with Long-COVID. Understanding experiences informs areas for future study. Research into the experience of POTS is emerging, with no currently published studies including the experiences of health professionals.

AIM: This study aimed to understand experiences of POTS, its challenges, and aspects of care from the perspectives of people with the condition and health professionals who look after them.

DESIGN: A grounded theory approach was taken to develop a conceptual framework of the experience of POTS conceptualised through a critical realist lens.

SETTING: This United Kingdom based study included people with POTS from three national health care centres and a diverse range of health professionals.

PARTICIPANTS: Theoretical and purposive sampling recruited people with POTS, and snowball sampling recruited health professionals through a United Kingdom charity and arrhythmia nursing network. Health professionals were interviewed from a range of professions including nurses, secondary care consultants, primary care general practitioners, psychologists, physiotherapists, and an occupational therapist.

METHOD: Between September 2021 and September 2022 in-depth online semi-structured interviews were undertaken. Data were thematically analysed. Corbin and Strauss' Grounded Theory methods of constant comparison, memos, and a reflexive journal were used. Analysis moved from first open coding of health professional themes to more focused axial coding, data, and category linking. The study patient and public involvement group informed thematic development and theoretical sampling. The final themes were conceptualised through the critical realism's three layers of experience.

RESULTS: Forty-four participants were included, 19 people with POTS and 25 health professionals. Three core themes were found: 1) A challenging condition, 2) POTS healthcare provision - services by accident not design, and 3) The need to validate experiences. Health professionals experienced challenges in their clinical self-efficacy. POTS care was driven by individual human agency and interpersonal relationships. People with POTS took individual responsibility for their self-management but were impacted by gender inequalities, a medical model prioritising guidelines, and a poor evidence-base.

CONCLUSION: This is the first qualitative study to explore both people with POTS and health professional experiences of looking after people with this condition. Findings identified: 1) a need for empowering both people with POTS and health professionals through shared care and decision making, 2) the requirement for a system wide recognition of POTS to move the landscape away from one of individual responsibility, and 3) the need to develop the evidence-base.

REGISTRATION: Health Research Authority (IRAS: 281284). First recruitment: 13/09/2021.

TWEETABLE ABSTRACT: Understanding the experiences of people with POTS and the health professionals who see them. The findings of 44 in-depth interviews.}, } @article {pmid39917870, year = {2024}, author = {Aveling, EL and Caldas, B and Sabaine, B and Portela, MC and Soares, L and Cornish, F}, title = {A cycle of invisibilisation: a qualitative study of Brazilian health system factors shaping access to long COVID care.}, journal = {BMJ global health}, volume = {9}, number = {12}, pages = {}, doi = {10.1136/bmjgh-2024-017017}, pmid = {39917870}, issn = {2059-7908}, mesh = {Humans ; Brazil ; *Health Services Accessibility ; *COVID-19 ; *Qualitative Research ; SARS-CoV-2 ; Male ; Female ; Delivery of Health Care ; }, abstract = {INTRODUCTION: Long COVID (LC), an often-debilitating infection-associated chronic condition (IACC), affects millions of people globally. Globally, LC patients struggle to access timely, appropriate care, often experiencing disbelief, misunderstandings or being diverted from healthcare. Few studies have examined health system factors influencing LC healthcare access, especially in the Global South. Drawing on the concept of candidacy, we examine health system factors influencing access to LC care in Brazil's public healthcare system (Sistema Único de Saúde, SUS) and theorise implications for equitable access to public healthcare for IACCs globally.

METHODS: We conducted a patient-engaged, qualitative study in the city of Rio de Janeiro. 29 individual semi-structured interviews were conducted with SUS professionals from administrative leaders to multidisciplinary primary and specialist care staff (November 2022 to July 2023). Verbatim transcripts were analysed using a pragmatic thematic analysis.

RESULTS: LC patients' candidacy for care is invisibilised within SUS through multiple, interacting processes. Interplay of an over-burdened health system, prioritisation of resources in response to (flawed) evidence of demand, misalignment of LC patient capacities and demands of navigating fragmented services, complex referral processes, professionals' lack of LC knowledge and disregard of the severity and morbidity of a chronic condition amid acute demands, led to the under-recognition of LC by healthcare professionals. Professionals' under-recognition perpetuates administrators' de-prioritisiation of resources, policies and training necessary to ensure access to appropriate care, creating a cycle of invisibilisation.

CONCLUSION: Urgent action to disrupt a cycle of invisibilisation is essential to mitigate patients' suffering and intensification of inequalities. Disrupting this pernicious cycle requires more than narrow clinical education efforts. Improved surveillance, education, patient involvement, attention to moral injury and building on existing multidisciplinary strengths may enhance access to LC care. Doing so offers wider benefits beyond patients with LC. We call for a paradigm shift in clinical approaches to IACCs.}, } @article {pmid39917633, year = {2025}, author = {Kumar, M and Baig, MS and Bhardwaj, K}, title = {Advancements in the development of antivirals against SARS-Coronavirus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1520811}, pmid = {39917633}, issn = {2235-2988}, mesh = {*Antiviral Agents/pharmacology/therapeutic use ; Humans ; *SARS-CoV-2/drug effects ; Animals ; *COVID-19 Drug Treatment ; COVID-19/epidemiology ; Severe acute respiratory syndrome-related coronavirus/drug effects/pathogenicity ; Severe Acute Respiratory Syndrome/drug therapy/virology/epidemiology ; Drug Development ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.}, } @article {pmid39917434, year = {2024}, author = {Almeida, GG and Alkan, S and Hoepner, R and Euler, A and Diem, L and Wagner, F}, title = {Chronic fatigue and headache in post-COVID-19 syndrome: a radiological and clinical evaluation.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1526130}, pmid = {39917434}, issn = {1664-2295}, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused millions of infections and deaths globally. Post-COVID-19 syndrome, or long COVID is characterized by lingering symptoms such as chronic fatigue, headaches, and sleep disturbances. This study aimed to investigate the correlation between these symptoms and T2-hyperintense white matter lesions detected on magnetic resonance imaging (MRI) of the brain and spine in patients with post-COVID-19 syndrome.

METHODS: This retrospective, single-center study analyzed a sample of 96 patients from Bern University Hospital in Switzerland who presented with suspected post-COVID-19 syndrome between 2020 and 2022. Patients completed self-report questionnaires evaluating fatigue, emotional wellbeing, and daytime sleepiness. Brain and spine MRIs were independently rated by 2 neuroradiologists for T2-hyperintense lesions. The correlation between these lesions and symptoms of fatigue and headache was assessed.

RESULTS: The cohort consisted predominantly of women (73%) with an average age of 46 years. Chronic fatigue (90%), sleep disorders (51%), and headache (57%) were the most prevalent symptoms. The fatigue questionnaires indicated high levels of fatigue. Brain MRI revealed T2-hyperintense lesions in 72% of patients, whereas spine MRI showed these lesions in only 16%. There was no statistically significant correlation between the presence of cerebral T2-hyperintense lesions and symptoms of fatigue (p = 0.815) or headaches (p = 0.178). Similarly, no significant correlation was found when considering numbers of pathological brain lesions (fatigue: p = 0.557; headaches: p = 0.820).

CONCLUSION: While T2-hyperintense lesions are common in patients with post-COVID-19 syndrome, their presence does not correlate significantly with symptoms of fatigue or headaches. These findings suggest that T2-hyperintense brain lesions may not be directly related to the subjective experience of these symptoms. Further research with larger sample sizes and adjustment for potential confounding factors is necessary to better understand the relationship between MRI findings and post-COVID-19 syndrome symptoms.}, } @article {pmid39917335, year = {2025}, author = {Brandstetter Figueroa, E and Frosch, AEP and Burrack, KS and Dileepan, G and Goldsmith, R and Harris, M and Ikeogu, N and Jibrell, H and Thayalan, S and Dewar, RL and Shenoy, C and Sereti, I and Baker, JV}, title = {Viral Burden and Illness Severity During Acute SARS-CoV-2 Infection Predict Persistent Long COVID Symptoms.}, journal = {Open forum infectious diseases}, volume = {12}, number = {2}, pages = {ofaf048}, pmid = {39917335}, issn = {2328-8957}, abstract = {BACKGROUND: Long COVID is a common complication of infection with severe acute respiratory syndrome coronavirus 2, but the prevalence and predictors of the condition remain poorly characterized.

METHODS: We prospectively studied adults (≥18 years) with acute coronavirus disease 2019 (COVID-19) presenting to an urban safety net hospital and associated clinics between July 2020 and December 2022. Logistic regression models were used to evaluate the association between baseline demographic, clinical, and laboratory characteristics with long COVID status, defined as symptoms persisting at least 9 months after acute disease. Among unrecovered participants, we describe the prevalence of individual symptoms.

RESULTS: We enrolled 222 participants, 162 (73%) of whom had known recovery status by 9 months. Median age was 54 years, half (55%) were female, and the majority of participants (78%) had at least 1 comorbidity at the time of COVID-19 diagnosis. Based on acute illness characteristics, the adjusted odds ratio for long COVID was 3.0 (95% confidence interval [CI], 1.1-8.0) among those with detectable nucleocapsid antigen and 3.6 (95% CI, 1.2-11) for those who required supplemental oxygen. Of the 41% of participants with symptoms persisting at least 9 months, central nervous system and psychological symptoms were most commonly reported, with 57% reporting functional limitations due to their persistent symptoms.

CONCLUSIONS: The strong association with initial disease suggests a decreasing prevalence of long COVID as acute illnesses become milder. However, many contemporary patients still experience high viral burden with extended viral replication, even after vaccination. Our findings highlight the importance of properly characterizing long COVID as viral evolution shifts acute disease presentation.}, } @article {pmid39915384, year = {2025}, author = {Oberhofer, E}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {2}, pages = {12-13}, doi = {10.1007/s15006-025-4620-5}, pmid = {39915384}, issn = {1613-3560}, } @article {pmid39914274, year = {2025}, author = {Honda-Okubo, Y and Sajkov, D and Wauchope, B and Turner, JV and Vote, B and Antipov, A and André, G and Lebedin, Y and Petrovsky, N}, title = {Immunogenicity and safety study of a single dose of SpikoGen® vaccine as a heterologous or homologous intramuscular booster following a primary course of mRNA, adenoviral vector or recombinant protein COVID-19 vaccine in ambulatory adults.}, journal = {Vaccine}, volume = {49}, number = {}, pages = {126744}, doi = {10.1016/j.vaccine.2025.126744}, pmid = {39914274}, issn = {1873-2518}, abstract = {BACKGROUND: SpikoGen® is a subunit recombinant Wuhan spike protein produced in insect cells and formulated with Advax-CpG55.2™ adjuvant. It is approved for adult and pediatric use in the Middle East. This study tested the safety and immunogenicity of SpikoGen® as a 3rd, 4th or 5th dose booster following a primary immunisation course of mRNA, adenovirus or SpikoGen® vaccine.

METHODS: The trial recruited participants who had received a previous doses of COVID-19 vaccine more than 3 months prior. Each received a single intramuscular booster dose of SpikoGen® vaccine. Spike and nuclear protein antibody levels were measured at 1 and 3 months post-booster, together with collection of data on SARS-CoV-2 breakthrough infections and symptoms of long COVID.

RESULTS: One-month post-booster, anti-spike IgG, sVNT, and pVNT levels were increased in all groups and there was ∼4-fold neutralizing antibodies against the heterologous Omicron BA.2 and BA.4/5 strains. The SpikoGen®-prime group had the highest levels of anti-spike IgG3, consistent with the Advax-CpG adjuvant driving IgG3 induction. There was no effect of age on the vaccine response. The booster dose was well tolerated with no vaccine-associated serious adverse events. Nine participants (9/74, 12.2 %) had a breakthrough SARS-CoV-2 infection between 2 weeks and 3 months post-booster. No long COVID was observed after breakthrough infections. Breakthrough infection was negatively correlated with baseline anti-nuclear protein IgG seropositivity.

CONCLUSION: A single SpikoGen® booster was well tolerated and stimulated cross- antibody responses against Omicron variants, regardless of the primary vaccine course received. With SARS-CoV-2 variants continuing to evolve, ongoing research is needed into optimum booster strategies.

CLINICALTRIALS: gov registration. NCT05542862.}, } @article {pmid39914235, year = {2025}, author = {Calvani, R and Marzetti, E and Tosato, M and Giampaoli, O and De Rosa, M and Marini, F}, title = {Reply - Letter to the editor - 'Beetroot juice intake positively influenced gut microbiota and inflammation but failed to improve functional outcomes in adults with Long COVID'.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {46}, number = {}, pages = {133-135}, doi = {10.1016/j.clnu.2025.01.033}, pmid = {39914235}, issn = {1532-1983}, } @article {pmid39913532, year = {2025}, author = {Owen, R and Ashton, RE and Bewick, T and Copeland, RJ and Ferraro, FV and Kennerley, C and Phillips, BE and Maden-Wilkinson, T and Parkington, T and Skipper, L and Thomas, C and Arena, R and Formenti, F and Ozemek, C and Veluswamy, SK and Gururaj, R and Faghy, MA}, title = {Profiling the persistent and episodic nature of long COVID symptoms and the impact on quality of life and functional status: a cohort observation study.}, journal = {Journal of global health}, volume = {15}, number = {}, pages = {04006}, doi = {10.7189/jogh.15.04006}, pmid = {39913532}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Quality of Life ; Female ; Male ; Middle Aged ; Prospective Studies ; Aged ; *Post-Acute COVID-19 Syndrome ; *Functional Status ; Adult ; Patient Reported Outcome Measures ; Cohort Studies ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {BACKGROUND: Post-viral issues following acute infection with coronavirus disease 2019 (COVID-19), referred to widely as long COVID, are associated with episodic, persistent, and disabling symptoms affecting quality of life and functional status. Evidence demonstrates a significant impairment and long disease course, but there remains limited empirical data to profile and determine the fluctuating symptom profile of long COVID.

METHODS: We devised a 16-week, multicentre prospective cohort observation study to profile changes in patient-reported outcomes, and biological, physiological, psychological, and cognitive parameters following diagnosis and/or referral to an established long COVID clinic. Following baseline assessments, participants completed four face-to-face visits interspersed with telephone consultations. Face-to-face visits included physiological assessment, patient-reported outcome measures (PROMs), functional status, and respiratory function. Telephone consultations involved PROMs and symptom profiling.

RESULTS: Patient-reported outcomes improved from baseline to week sixteen, but demonstrated between visit fluctuations in frequency and severity. Further findings highlight the severity and frequency of long COVID symptom profiles and the extent of quality of life and functional status impairment.

CONCLUSIONS: The data presented here highlight the episodic and relapsing nature and should be used to help characterise long COVID disability. They can inform the development of long COVID-specific guidelines and support services that can adequately respond to the reductions in patient well-being.}, } @article {pmid39912705, year = {2025}, author = {Stodell, M}, title = {We still know little about long COVID.}, journal = {Journal of the Royal Society of Medicine}, volume = {}, number = {}, pages = {1410768241309753}, doi = {10.1177/01410768241309753}, pmid = {39912705}, issn = {1758-1095}, } @article {pmid39911555, year = {2024}, author = {Taube, M and Lesiņa, AA}, title = {Case report: Development of anxiety symptoms after receiving the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine: a case series.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1514428}, pmid = {39911555}, issn = {1664-0640}, abstract = {Severe acute respiratory sindrome - Coronavirus - 2 (SARS-CoV-2) (Coronavirus disease - 19 (COVID-19)) infection can result in long-term health consequences, such as long COVID. The clinical manifestations of long COVID include depression, anxiety, brain fog with cognitive dysfunction, memory issues, and fatigue. However, the links between vaccination and psychiatric disorders have been less studied. This article describes three patients who reported anxiety after receiving a complete course of the Pfizer-BioNTech BNT162b2 vaccine. It is important to explore the relationship between anxiety, other mental health disorders, and COVID-19 vaccination, as well as to investigate potential pathogenetic mechanisms.}, } @article {pmid39911045, year = {2025}, author = {Schmitz, S and Alvarez-Vaca, D and Weiss, J and Pires, SM and Masi, S and Debacker, M and Alkerwi, A}, title = {Widening the scope for the burden of COVID-19 - Comorbidities and long COVID: an analysis of the three pandemic years in Luxembourg.}, journal = {European review for medical and pharmacological sciences}, volume = {29}, number = {1}, pages = {39-52}, doi = {10.26355/eurrev_202501_37058}, pmid = {39911045}, issn = {2284-0729}, mesh = {*COVID-19/epidemiology ; Humans ; Luxembourg/epidemiology ; *Comorbidity ; *SARS-CoV-2 ; Cost of Illness ; Disability-Adjusted Life Years ; Male ; Female ; Pandemics ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; Mortality, Premature/trends ; }, abstract = {OBJECTIVE: Burden of disease studies evaluate the direct impact of disease in terms of morbidity and premature mortality over a given time horizon. The objective of this study was to estimate the burden of COVID-19 in Luxembourg during the first three years of the pandemic, with a particular focus on methodologies applied to two areas of high uncertainty: post-acute consequences (PAC) of COVID-19 and the disparity of associated pathologies to COVID-19 deaths compared to other causes of deaths.

MATERIALS AND METHODS: Epidemiological monitoring data on screening, hospital admission, and mortality associated with COVID-19 were used to estimate disability-adjusted life years (DALYs). Years of Life lost due to premature death (YLL) estimates have been adjusted for the impact of comorbidity profiles from cause-of-death data using the Charlson Comorbidity Index (CCI). In the absence of a PAC-specific disability weight, a symptom-based approach using data from a national cohort study was applied and compared with alternative weights used in the literature. A one-by-one sensitivity analysis was performed to evaluate the uncertainty associated with each model parameter.

RESULTS: The total burden of COVID-19, including PAC, over three years, was estimated at 17,801 DALYs, combining 14,903 YLLs and 2,898 YLDs (Years of Healthy Life lived with Disability). Comorbidity adjustment led to an average reduction of 9% in YLL estimates. Alternative choices for PAC led to an up to 3-fold increase in YLD compared to our base case estimates. Prevalence, disability weight, and duration of PAC were the most influential parameters identified in the sensitivity analysis.

CONCLUSIONS: The COVID-19 pandemic has produced a significant burden on the resident population in Luxembourg. Adjusting for comorbidities is an important step in assessing the burden of COVID-19. The uncertainty associated with PAC parameters has highlighted the need for further research to standardize the definition of the prevalence, duration, and severity of this condition. The suggested symptom-based approach presents a flexible option until PAC-specific disability weights are derived in the future.}, } @article {pmid39910970, year = {2025}, author = {Tudorache Pantazi, MA and Gadea-Doménech, M and Espert Tortajada, R}, title = {[Cognition and Long COVID: A PRISMA Systematic Review of Longitudinal Studies].}, journal = {Revista de neurologia}, volume = {79}, number = {12}, pages = {37385}, doi = {10.31083/RN37385}, pmid = {39910970}, issn = {1576-6578}, mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Cognition ; Cognitive Dysfunction/etiology ; Time Factors ; }, abstract = {INTRODUCTION: Long COVID is defined by National Institute for Health and Care Excellence (NICE) as the set of signs and symptoms that develop during or after a SARS-CoV-2 infection and continue for more than twelve weeks without any alternative diagnosis. One of the most frequent persistent symptoms reported by patients and verified in neuroimaging studies is cognitive dysfunction, due to a generalized hypoconnectivity and a diffuse axonal lesion in white matter. Therefore, the objectives of the present review are to determine how long cognitive functions remain affected during Long COVID and to explore which cognitive functions are most affected beyond three months of follow-up in patients up to 65 years of age without previous neuropsychological or psychiatric complications.

METHODS: A systematic review was performed using PRISMA criteria and 11 articles were included through a comprehensive search of five different databases: PubMed, Medline, Scopus, WOS and ProQuest. The risk of bias of the articles was assessed using the Newcastle-Ottawa scale.

RESULTS: Cognitive problems in Long COVID persist over time and improve slowly, although studies seem to agree that most areas improved significantly after one year. The cognitive functions that remained impaired the longest were processing speed and attention.

CONCLUSIONS: These cognitive alterations cause a reduction in the quality of life of the patients and a reduction in work capacity and manifest the need for a cognitive intervention.}, } @article {pmid39910549, year = {2025}, author = {Yang, XJ and Zhang, LB and Wang, LL and Deng, H and Li, YL and Zhao, RJ and Xu, JY and Yang, YC and Zhou, SJ}, title = {Status and risk factors for depression, anxiety, and insomnia symptoms among adolescents in the post-pandemic era.}, journal = {BMC public health}, volume = {25}, number = {1}, pages = {471}, pmid = {39910549}, issn = {1471-2458}, abstract = {BACKGROUND: Owing to their vulnerability to public health crises, adolescents' mental health status, and related risk factors in the post-pandemic era in China require examination. This study aimed to lay a foundation for subsequent interventions and mental disorder prevention among adolescents.

METHODS: An anonymous online survey was conducted January 8-18, 2023. The survey comprised two parts. The first part collected personal information. The second part included the nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder Scale, and Pittsburgh Sleep Quality Index.

RESULTS: Of 50,666 adolescent participants, 46.8% displayed depressive symptoms, 31.5% showed anxiety symptoms, and 47.9% experienced difficulties initiating sleep within 30 min, while 4.9% manifested depressive, anxiety, and insomnia symptoms simultaneously. Chi-square tests revealed significant variations in the prevalence of these conditions according to age, sex, coronavirus disease-2019 (COVID-19) infection status, family infection status, and increased screen time (P < 0.001). Logistic regression analysis indicated heightened rates of depression, anxiety, and insomnia symptoms among rural adolescents, females, those aged 16-18 years, individuals with a history of COVID-19, those with a long COVID-19 illness, and those with increased screen time (all P < 0.001).

CONCLUSION: The mental health status of adolescents in the post-pandemic era should be taken seriously, particularly that of females, high school students, and adolescents with increased use of electronic screens. Among such efforts, school administrators should strengthen their connection with psychologists, as early identification and intervention in adolescents are important for preventing school crises.}, } @article {pmid39909170, year = {2025}, author = {Low, ZXB and Yong, SJ and Alrasheed, HA and Al-Subaie, MF and Al Kaabi, NA and Alfaresi, M and Albayat, H and Alotaibi, J and Al Bshabshe, A and Alwashmi, ASS and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alharthi, H and Al Ali, HA and Almoumen, AA and Alqasimi, NA and AlSaihati, H and Rodriguez-Morales, AJ and Rabaan, AA}, title = {Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {111279}, doi = {10.1016/j.pnpbp.2025.111279}, pmid = {39909170}, issn = {1878-4216}, abstract = {RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.

OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.

RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.

CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.}, } @article {pmid39907931, year = {2025}, author = {Eastin, EF and Machnik, JV and Stiles, LE and Larsen, NW and Seliger, J and Geng, LN and Bonilla, H and Yang, PC and Miglis, MG}, title = {Chronic autonomic symptom burden in long-COVID: a follow-up cohort study.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {}, number = {}, pages = {}, pmid = {39907931}, issn = {1619-1560}, abstract = {PURPOSE: Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an established online cohort of participants with LC to assess duration and severity of autonomic dysfunction, impact on quality of life, risk factors of autonomic diagnoses including postural tachycardia syndrome (POTS), and efficacy of common treatments.

METHODS: Our international cohort included 526 adults with LC aged 20-65 years who previously completed baseline evaluations of LC symptoms, autonomic symptom burden, and quality of life. Participants repeated survey instruments and completed new instruments assessing risk factors and symptom mitigation strategies. A subset of individuals completed a 10-min active stand test. Multivariable logistic regression identified predictors of autonomic symptom burden and incident autonomic diagnoses including POTS.

RESULTS: A total of 71.9% of participants with LC had a Composite Autonomic Symptom Score-31 (COMPASS-31) score ≥ 20, suggestive of moderate-to-severe autonomic dysfunction. The median symptom duration was 36 [30-40] months, and 37.5% of participants could no longer work or had to drop out of school due to their illness. In addition, 40.5% of individuals with autonomic dysfunction were newly diagnosed with POTS, representing 33% of the total LC cohort. Female sex and joint hypermobility were associated with an increased risk of autonomic dysfunction.

CONCLUSIONS: Evidence of chronic moderate-to-severe autonomic dysfunction was seen in most participants with LC in our cohort and was significantly associated with reduced quality of life and functional disability. POTS was the most common post-COVID autonomic diagnosis.}, } @article {pmid39907495, year = {2025}, author = {Mandel, H and Yoo, YJ and Allen, AJ and Abedian, S and Verzani, Z and Karlson, EW and Kleinman, LC and Mudumbi, PC and Oliveira, CR and Muszynski, JA and Gross, RS and Carton, TW and Kim, C and Taylor, E and Park, H and Divers, J and Kelly, JD and Arnold, J and Geary, CR and Zang, C and Tantisira, KG and Rhee, KE and Koropsak, M and Mohandas, S and Vasey, A and Mohammad Mosa, AS and Haendel, M and Chute, CG and Murphy, SN and O'Brien, L and Szmuszkovicz, J and Guthe, N and Santana, JL and De, A and Bogie, AL and Halabi, KC and Mohanraj, L and Kinser, PA and Packard, SE and Tuttle, KR and Hirabayashi, K and Kaushal, R and Pfaff, E and Weiner, MG and Thorpe, LE and Moffitt, RA}, title = {Long-COVID incidence proportion in adults and children between 2020 and 2024.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf046}, pmid = {39907495}, issn = {1537-6591}, abstract = {BACKGROUND: Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes).

METHODS: This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis.

RESULTS: Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants.

CONCLUSION: Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management.}, } @article {pmid39907423, year = {2025}, author = {Araújo, FC and Amaral, ACD and Silva, HJ and Santos, JNV and Mendonça, VA and Oliveira, VC and Rocha-Vieira, E}, title = {Autoantibodies as potential prognostic factors for clinical outcomes related to COVID-19: a systematic review of inception prospective cohort studies with GRADE recommendations.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {58}, number = {}, pages = {e13965}, doi = {10.1590/1414-431X2024e13965}, pmid = {39907423}, issn = {1414-431X}, mesh = {Humans ; *COVID-19/immunology/mortality ; *Autoantibodies/blood ; Prognosis ; *SARS-CoV-2/immunology ; Prospective Studies ; }, abstract = {This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.}, } @article {pmid39907353, year = {2025}, author = {Prediger, KM and Ribeiro, AC and Uehara, SCDSA}, title = {Prevalent symptoms and characteristics of the Long COVID-19 population: a scoping review.}, journal = {Revista latino-americana de enfermagem}, volume = {33}, number = {}, pages = {e4479}, doi = {10.1590/1518-8345.7353.4479}, pmid = {39907353}, issn = {1518-8345}, mesh = {Female ; Humans ; Male ; *COVID-19/epidemiology ; Dyspnea/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Sex Factors ; }, abstract = {UNLABELLED: to map the scientific literature on the clinical and demographic characteristics of Long COVID-19. this is a scoping review based on the principles recommended by the JBI and the PRISMA guidelines for data extraction, carried out on four databases. The PCC strategy was used for data collection, and the results were described and diagrammed. The studies were selected after removing duplicates, individual and peer review. an analysis of the 13 articles selected showed that Long COVID affects all age groups and people of both sexes, presenting a multiplicity of symptoms, such as fatigue (61.5%), dyspnea (46.1%), changes in smell and/or taste (38.6%), anxiety (15.3%) and cognitive impairment (30.7%). Females were found to be at increased risk of developing Long COVID. identifying the symptoms prevalent in Long COVID contributes to public health strategies for diagnosing and assisting people affected by the disease. Future studies are recommended on the approach to the persistence of symptoms in Long COVID and the relationship between adherence to the vaccination schedule against COVID-19, gender, race/ethnicity, degree of susceptibility in the different age groups, level of education and income, as well as the most recurrent comorbidities in the population.

BACKGROUND: (1) It was found that Long COVID affects all age groups of both sexes. (2) Most common symptoms: fatigue, dyspnea and altered sense of smell and/or taste. (3) Risk factors: female gender, COVID-19 severity and comorbidities.}, } @article {pmid39906532, year = {2025}, author = {Sivan, M and Greenwood, DCC and Smith, T}, title = {Long covid as a long term condition.}, journal = {BMJ medicine}, volume = {4}, number = {1}, pages = {e001366}, pmid = {39906532}, issn = {2754-0413}, } @article {pmid39904524, year = {2025}, author = {Jones, F and Busse, M and Rowe, C and Domeney, A and Patel, I}, title = {We must recognise the collective wisdom of those with lived experience of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {388}, number = {}, pages = {r243}, doi = {10.1136/bmj.r243}, pmid = {39904524}, issn = {1756-1833}, } @article {pmid39904520, year = {2025}, author = {Soff, S and Yoo, YJ and Bramante, C and Reusch, JEB and Huling, JD and Hall, MA and Brannock, D and Sturmer, T and Butzin-Dozier, Z and Wong, R and Moffitt, R and , }, title = {Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C).}, journal = {BMJ open diabetes research & care}, volume = {13}, number = {1}, pages = {}, doi = {10.1136/bmjdrc-2024-004536}, pmid = {39904520}, issn = {2052-4897}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications ; *COVID-19/complications/mortality/epidemiology ; Female ; Male ; Middle Aged ; *Glycemic Control ; Retrospective Studies ; *Glycated Hemoglobin/analysis ; Aged ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Blood Glucose/analysis ; Risk Factors ; }, abstract = {INTRODUCTION: Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear.

OBJECTIVE: Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30-180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control.

RESULTS: Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to <10% (OR 1.20, 95% CI 1.02 to 1.41) and ≥10% (OR 1.40, 95% CI 1.14 to 1.72) compared with those with HbA1c 6.5% to <8%. This association was not seen in the COVID-negative group. Higher HbA1c levels were associated with increased risk of Long COVID symptoms, especially respiratory and brain fog. There was no association between HbA1c levels and risk of death within 30-180 days following COVID-19. NLP identified more patients with Long COVID symptoms compared with diagnosis codes.

CONCLUSION: Poor glycemic control (HbA1c≥8%) in people with T2D was associated with higher risk of Long COVID symptoms 30-180 days following COVID-19. Notably, this risk increased as HbA1c levels rose. However, this association was not observed in patients with T2D without a history of COVID-19. An NLP-based definition of Long COVID identified more patients than diagnosis codes and should be considered in future studies.}, } @article {pmid39902608, year = {2025}, author = {Tcheroyan, R and Makhoul, P and Simpson, S}, title = {An updated review of pulmonary radiological features of acute and chronic pulmonary COVID-19.}, journal = {Current opinion in pulmonary medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCP.0000000000001152}, pmid = {39902608}, issn = {1531-6971}, abstract = {PURPOSE OF REVIEW: Significant progress has been made in our understanding of the acute and chronic clinical and radiological manifestations of coronavirus-19 (COVID-19). This article provides an updated review on pulmonary COVID-19, while highlighting the key imaging features that can identify and distinguish acute COVID-19 pneumonia and its chronic sequelae from other diseases.

RECENT FINDINGS: Acute COVID-19 pneumonia typically presents with manifestations of organizing pneumonia on computed tomography (CT). In cases of severe disease, patients clinically progress to acute respiratory distress syndrome, which manifests as diffuse alveolar damage on CT. The most common chronic imaging finding is ground-glass opacities, which commonly resolves, as well as subpleural bands and reticulation. Pulmonary fibrosis is an overall rare complication of COVID-19, with characteristic features, including architectural distortion, and traction bronchiectasis.

SUMMARY: Chest CT can be a helpful adjunct tool in both diagnosing and managing acute COVID-19 pneumonia and its chronic sequelae. It can identify high-risk cases and guide decision-making, particularly in cases of severe or complicated disease. Follow-up imaging can detect persistent lung abnormalities associated with long COVID and guide appropriate management.}, } @article {pmid39902344, year = {2024}, author = {Schwendinger, F and Infanger, D and Maurer, DJ and Radtke, T and Carrard, J and Kröpfl, JM and Emmenegger, A and Hanssen, H and Hauser, C and Schwehr, U and Hirsch, HH and Ivanisevic, J and Leuzinger, K and Martinez, AE and Maurer, M and Sigrist, T and Streese, L and von Känel, R and Hinrichs, T and Schmidt-Trucksäss, A}, title = {Medium- to long-term health condition of patients post-COVID-19, exercise intolerance and potential mechanisms: A narrative review and perspective.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241296701}, pmid = {39902344}, issn = {2050-3121}, abstract = {BACKGROUND: Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.

RESULTS: Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6 months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.

CONCLUSION: Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.

CONDENSED ABSTRACT: This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.}, } @article {pmid39902266, year = {2025}, author = {}, title = {Erratum: "Effect of lactoferrin treatment on symptoms and physical performance in long COVID patients: a randomised, double-blind, placebo-controlled trial". Anne-Lotte Redel, Fatana Miry, Merel Elise Hellemons, Laurien Maria Amarentia Oswald and Gerrit Johannes Braunstahl. ERJ Open Res 2024; 10: 00031-2024.}, journal = {ERJ open research}, volume = {11}, number = {1}, pages = {}, doi = {10.1183/23120541.50031-2024}, pmid = {39902266}, issn = {2312-0541}, abstract = {[This corrects the article DOI: 10.1183/23120541.00031-2024.].}, } @article {pmid39901596, year = {2025}, author = {Öztürk, F and Emiroğlu, C and Aypak, C}, title = {The Relationship Between Long Covid Symptoms and Vaccination Status in COVID-19 Survivors.}, journal = {Journal of evaluation in clinical practice}, volume = {31}, number = {1}, pages = {e70004}, doi = {10.1111/jep.70004}, pmid = {39901596}, issn = {1365-2753}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Male ; Female ; Middle Aged ; Retrospective Studies ; *COVID-19 Vaccines/administration & dosage ; *SARS-CoV-2 ; Survivors ; Adult ; Aged ; Vaccination/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The positive effects of vaccination status on the course of Long COVID symptoms have not been fully elucidated. Our aim is to determine the most common Long COVID symptoms in patients monitored in the COVID-19 follow-up clinic and to examine whether there is a difference between the recovery rates of those who are vaccinated and those who are not vaccinated.

METHOD: Between December 1, 2020 and April 30, 2022, prospectively collected data of 916 patients who were admitted to the COVID-19 follow-up outpatient clinic of a tertiary hospital for the first time were evaluated as a retrospective cohort in this study. The frequencies of the ten most common symptoms in the first and last examinations of 478 patients with Long COVID symptoms were determined, and their recovery was compared. Patients were divided into two groups according to their vaccination status. The values showing the recovery rates obtained for these two groups were compared between themselves again.

RESULTS: The average age of the patients in the study group was 54.43 ± 11.71 years, and 255 (53.3%) were male. The median follow-up period was 10 months. 84.7% of patients had received at least one dose of vaccine. Statistically significant results were found for improvement in all ten symptoms in vaccinated patients compared to the never-vaccinated group. There was no statistically significant difference between the CoronaVac, BNT162b2, and heterologous (CoronaVac+ BNT162b2) vaccine groups. Factors affecting recovery for the three most common symptoms (dyspnea, fatigue, forgetfulness) were examined with univariate logistic regression analysis, and only vaccination or non-vaccination was found to be a significant risk factor.

CONCLUSION: This study showed that receiving vaccination may be effective in improving Long COVID symptoms. Although there were no statistically significant differences between the inactive vaccine CoronaVac, the mRNA vaccine BNT162b2, and the heterologous (CoronaVac+ BNT162b2) vaccine in terms of reducing Long COVID symptoms, higher recovery rates were detected in those who received the mRNA vaccine BNT162b2.}, } @article {pmid39901563, year = {2025}, author = {Mazer, B and Haynes, S and Ficara, V and Streib, A and St-Jean, D and Spiridigliozzi, AM and Minichiello, R and Ehrmann Feldman, D}, title = {Rehabilitation service utilization among individuals with long COVID in Laval, Canada.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/09638288.2025.2459894}, pmid = {39901563}, issn = {1464-5165}, abstract = {PURPOSE: (1) investigate utilization of rehabilitation services (Physical Therapy [PT], Occupational Therapy [OT], Speech Language Pathology [SLP], and Psychology [Psych]) among adults with long-COVID in Laval, Quebec; (2) determine unmet needs; (3) determine factors associated with receiving services; (4) examine satisfaction.

MATERIALS AND METHODS: Using an electronic survey, participants completed the Newcastle Post-COVID Syndrome Follow-Up Screening Questionnaire, COVID-19 Yorkshire Rehabilitation Scale, and the COVID-19 Rehabilitation Needs Questionnaire. Descriptive statistics were used to describe rehabilitation services received, reasons for unmet needs, and satisfaction. Bivariate analysis and multivariable logistic regression were used to determine factors associated with receiving services.

RESULTS: Of 1031 persons with long-COVID, 37(3.6%) accessed OT, 80(7.8%) PT, 2(0.2%) SLP, and 63(6.1%) Psych. One quarter of participants who did not access rehabilitation services reported needing them. Factors associated with receiving services included hospitalization, vaccination, comorbidities, ≥1 year since COVID-19, female, ≥55 years, married/living together, and unemployed. Reasons for unmet needs were not knowing who to turn to, no referral, and financial. Most were satisfied with the services they received (70-84%).

CONCLUSION: The majority of participants with long-COVID did not access rehabilitation services to address their impairments and disabilities. Accessible, multidisciplinary rehabilitation services to address the functional needs of people with long COVID is needed.}, } @article {pmid39901510, year = {2025}, author = {Pasculli, P and Antonacci, M and Zingaropoli, MA and Dominelli, F and Ciccone, F and Pandolfi, F and Fosso Ngangue, YC and Masci, GM and Campagna, R and Iafrate, F and Panebianco, V and Catalano, C and Turriziani, O and Galardo, G and Palange, P and Mastroianni, CM and Ciardi, M}, title = {SARS-CoV-2 vaccination influence in the development of Long-COVID clinical phenotypes.}, journal = {Epidemiology and infection}, volume = {}, number = {}, pages = {1-21}, doi = {10.1017/S0950268825000093}, pmid = {39901510}, issn = {1469-4409}, } @article {pmid39468840, year = {2025}, author = {Lee, K and Park, J and Lee, J and Lee, H and Ha, Y and Yon, DK}, title = {Correspondence to editorial on "Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: a multinational population-based cohort study from South Korea, Japan, and the UK".}, journal = {Clinical and molecular hepatology}, volume = {31}, number = {1}, pages = {e87-e89}, doi = {10.3350/cmh.2024.0935}, pmid = {39468840}, issn = {2287-285X}, } @article {pmid39901177, year = {2025}, author = {Polli, A and Godderis, L and Martens, DS and Patil, MS and Hendrix, J and Wyns, A and Van Campenhout, J and Richter, E and Fanning, L and Vandekerckhove, O and Claeys, E and Janssens, W and Lorent, N}, title = {Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {60}, pmid = {39901177}, issn = {1741-7015}, abstract = {BACKGROUND: Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.

METHODS: Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).

RESULTS: Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.

CONCLUSIONS: Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.}, } @article {pmid39900737, year = {2025}, author = {Wang, M and Ye, C and Yang, Y and Mukasa, D and Wang, C and Xu, C and Min, J and Solomon, SA and Tu, J and Shen, G and Tang, S and Hsiai, TK and Li, Z and McCune, JS and Gao, W}, title = {Printable molecule-selective core-shell nanoparticles for wearable and implantable sensing.}, journal = {Nature materials}, volume = {}, number = {}, pages = {}, pmid = {39900737}, issn = {1476-4660}, support = {R21DK13266//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA239373//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01GM129863//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; RSG-21-181-01-CTPS//American Cancer Society (American Cancer Society, Inc.)/ ; N00014-21-1-2483//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; N00014-21-1-2845//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/ ; W911NF-23-1-0041//United States Department of Defense | United States Army | U.S. Army Research, Development and Engineering Command | Army Research Office (ARO)/ ; 80NSSC20M0167//National Aeronautics and Space Administration (NASA)/ ; }, abstract = {Wearable and implantable biosensors are pioneering new frontiers in precision medicine by enabling continuous biomolecule analysis for fundamental investigation and personalized health monitoring. However, their widespread adoption remains impeded by challenges such as the limited number of detectable targets, operational instability and production scalability. Here, to address these issues, we introduce printable core-shell nanoparticles with built-in dual functionality: a molecularly imprinted polymer shell for customizable target recognition, and a nickel hexacyanoferrate core for stable electrochemical transduction. Using inkjet printing with an optimized nanoparticle ink formulation, we demonstrate the mass production of robust and flexible biosensors capable of continuously monitoring a broad spectrum of biomarkers, including amino acids, vitamins, metabolites and drugs. We demonstrate their effectiveness in wearable metabolic monitoring of vitamin C, tryptophan and creatinine in individuals with long COVID. Additionally, we validate their utility in therapeutic drug monitoring for cancer patients and in a mouse model through providing real-time analysis of immunosuppressants such as busulfan, cyclophosphamide and mycophenolic acid.}, } @article {pmid39899641, year = {2025}, author = {Funk, M and Reinke, M and Löwe, B and Engelmann, P}, title = {Development of an expectation management intervention for patients with Long COVID: A focus group study with affected patients.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0317905}, doi = {10.1371/journal.pone.0317905}, pmid = {39899641}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *COVID-19/psychology/therapy ; Middle Aged ; Aged ; *Focus Groups ; Adult ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: A significant number of individuals who have contracted SARS-CoV-2 report persistent somatic symptoms after the infection has resolved. Evidence-based treatment options for Long COVID are lacking to date. To ensure that an expectation management intervention, designed for the research project SOMA.COV, addresses relevant patient needs as well as to promote treatment acceptance and adherence, a participatory approach was chosen.

OBJECTIVE: The aim of the present study was to explore needs and wishes of patients with Long COVID regarding the preliminary version of an expectation management intervention and to thereby inform the further development of the treatment manual.

METHODS: Twenty-two patients affected by Long COVID participated in one of four focus groups in June and July 2023. Participants were presented with the draft content of a four-session expectation management intervention. Feedback was audio-recorded, transcribed, and analyzed using thematic analysis.

RESULTS: Thirteen themes relating to the main components of the intervention manual were developed. Large parts of the manual received overall positive feedback, including psychoeducation on the biopsychosocial etiology of the condition, elements of cognitive restructuring, and an imagination exercise. Patients' response to the presented vicious circle of fear and a behavior change exercise was mixed. Modifications to the manual were made in response to patients' feedback.

CONCLUSION: Patients with Long COVID provided positive feedback on an expectation management intervention while also highlighting important adaptations necessary for this patient group. The study results informed the finalization of the treatment manual within the SOMA.COV project, which investigates the effectiveness of this intervention for patients with Long COVID in a three-armed randomized controlled trial.}, } @article {pmid39899316, year = {2025}, author = {Ford, ND and Vahratian, A and Pratt, CQ and Yousaf, AR and Gregory, CO and Saydah, S}, title = {Long COVID Prevalence and Associated Activity Limitation in US Children.}, journal = {JAMA pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamapediatrics.2024.6206}, pmid = {39899316}, issn = {2168-6211}, } @article {pmid39896874, year = {2025}, author = {Livieratos, A and Lockley, SW and Sotirios Tsiodras, }, title = {Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.}, journal = {EClinicalMedicine}, volume = {80}, number = {}, pages = {103073}, pmid = {39896874}, issn = {2589-5370}, abstract = {Chronic fatigue syndrome (CFS) remains a subject of scientific research specifically with regards to its association with infections, including the more recently described Long COVID condition. Chronic fatigue and sleep disturbances in Long COVID are intricately linked to disruptions in circadian rhythms, driven by distinct molecular and cellular mechanisms triggered by SARS-CoV-2 infection. This can be driven by various mechanisms including dysregulation of key clock genes (CLOCK, BMAL1, PER2), mitochondrial dysfunction impairing oxidative phosphorylation, and cytokine-induced neuroinflammation (e.g., interleukin-6, tumor necrosis factor-alpha). Epigenetic changes, including DNA methylation at clock-related loci, particularly in peripheral tissues, further contribute to systemic circadian dysregulation. This work underscores the multifaceted molecular and systemic disruptions to circadian regulation in relation to fatigue and sleep disturbances identified as post-infectious sequelae, focusing on the Long COVID condition.}, } @article {pmid39896706, year = {2025}, author = {Wu, DJ and Liu, N}, title = {Association of cognitive deficits with sociodemographic characteristics among adults with post-COVID conditions: Findings from the United States household pulse survey.}, journal = {Biology methods & protocols}, volume = {10}, number = {1}, pages = {bpaf006}, pmid = {39896706}, issn = {2396-8923}, abstract = {People infected with coronavirus disease-19 (COVID-19) may continue to experience symptoms for several weeks or even months after acute infection, a condition known as long COVID. Cognitive problems such as memory loss are among the most commonly reported symptoms of long COVID. However, a comprehensive evaluation of the risks of cognitive decline following COVID-19 infection among different sociodemographic groups has not been undertaken at the national level in the USA. We conducted a secondary analysis on the datasets from the U.S. Census Bureau Household Pulse Survey, encompassing data collected from 1 June 2022 to 19 December 2022. Based on a cohort of 385 370 individuals aged 18 years or older, we employed logistic regression analysis to examine the association between self-reported cognitive deficits and different sociodemographic factors among individuals with long COVID conditions. We have demonstrated that individuals with long COVID had a significantly higher risk of cognitive deficits compared to those with no history of COVID infection. Cognitive deficits vary across sociodemographic groups. In individuals without long COVID, men, older adults, and those with higher education reported fewer cognitive deficits, while Hispanics and residents of the South reported more. Long COVID had similar impacts across genders and regions but appeared to have the smallest impact on Hispanics compared to other racial groups. Conversely, the effects of long COVID were most significant in older adults and individuals with higher education. The state-level analysis further suggests potential variation in long COVID's effects across different states. The risks of cognitive deficits among adults with post-COVID conditions are substantial. Various sociodemographic groups can have different risks of developing cognitive deficits after experiencing long COVID. The findings of this large-scale study can help identify sociodemographic groups at higher risk of cognitive deficits, facilitate medical interventions, and guide resource allocation to target populations at risk and prioritize areas with a high rate of cognitive decline.}, } @article {pmid39895557, year = {2025}, author = {Khan, MS and Miller, AJ and Ejaz, A and Molinger, J and Goyal, P and MacLeod, DB and Swavely, A and Wilson, E and Pergola, M and Tandri, H and Mills, CF and Raj, SR and Fudim, M}, title = {Cerebral Blood Flow in Orthostatic Intolerance.}, journal = {Journal of the American Heart Association}, volume = {}, number = {}, pages = {e036752}, doi = {10.1161/JAHA.124.036752}, pmid = {39895557}, issn = {2047-9980}, abstract = {Cerebral blood flow (CBF) is vital for delivering oxygen and nutrients to the brain. Many forms of orthostatic intolerance (OI) involve impaired regulation of CBF in the upright posture, which results in disabling symptoms that decrease quality of life. Because CBF is not easy to measure, rises in heart rate or drops in blood pressure are used as proxies for abnormal CBF. These result in diagnoses such as postural orthostatic tachycardia syndrome and orthostatic hypotension. However, in many other OI syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and long COVID, heart rate and blood pressure are frequently normal despite significant drops in CBF. This often leads to the incorrect conclusion that there is nothing hemodynamically abnormal in these patients and thus no explanation or treatment is needed. There is a need to measure CBF, as orthostatic hypoperfusion is the shared pathophysiology for all forms of OI. In this review, we examine the literature studying CBF dysfunction in various syndromes with OI and evaluate methods of measuring CBF including transcranial Doppler ultrasound, extracranial cerebral blood flow ultrasound, near infrared spectroscopy, and wearable devices.}, } @article {pmid39893704, year = {2025}, author = {Takefuji, Y}, title = {Letter to editor-Beetroot juice intake positively influenced gut microbiota and inflammation but failed to improve functional outcomes in adults with Long COVID.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {46}, number = {}, pages = {117-118}, doi = {10.1016/j.clnu.2025.01.027}, pmid = {39893704}, issn = {1532-1983}, } @article {pmid39892623, year = {2025}, author = {Hejazian, SS and Vemuri, A and Sadr, AV and Shahjouei, S and Bahrami, S and Abedi, V and Zand, R}, title = {The Health-Related Quality of Life Among Stroke Survivors With Post-COVID Conditions Living in the United States.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {}, number = {}, pages = {108246}, doi = {10.1016/j.jstrokecerebrovasdis.2025.108246}, pmid = {39892623}, issn = {1532-8511}, abstract = {BACKGROUND AND AIM: It is widely recognized that a considerable number of COVID-19 survivors continue to experience post-COVID conditions (PCCs). Given that stroke survivors face a heightened risk of PCCs compared to the general population, our objective was to assess the impact of PCCs on the health-related quality of life (HRQL) among stroke survivors in the United States.

METHOD: We used the Behavioral Risk Factor Surveillance System data 2022. Respondents with a history of COVID-19 infection and stroke were selected and classified based on whether they experienced PCCs. Finally, the HRQL-related items, including self-reported general health (SRGH), the number of days with compromised mental and physical health, and the daily efficiency, were compared between the two groups.

RESULTS: Overall, 3988 respondents (42.8% aged above 64 years old, 45.8% men) were enrolled. Compared to stroke survivors without PCCs, those with PCCs had significantly worse SRGH and a higher number of days with compromised mental and physical health. However, although multivariate regression analysis supported the adverse impact of PCCs on the SRGH of stroke survivors, the results were not statistically significant (aOR=1.32,CI95%:[0.98-1.78],p=0.070). Fatigue and dyspnea emerged as the most significantly associated symptoms with impaired SRGH. Additionally, lower education and annual household income level, smoking, lack of physical activity, and comorbidities including diabetes, heart, and pulmonary disease were associated with a higher prevalence of unfavorable SRGH among stroke survivors with PCCs.

CONCLUSION: Our study highlights that PCCs might be associated with worse SRGH. Lower education, income, and physical activity, smoking, and comorbidities were associated with a higher rate of unfavorable SRGH among stroke survivors with PCCs.}, } @article {pmid39891865, year = {2025}, author = {Li, Q and Shi, X and Tang, Y and Fu, Y and Fu, X}, title = {Shared genes and relevant potential molecular linkages between COVID-19 and chronic thromboembolic pulmonary hypertension (CTEPH).}, journal = {Journal of thrombosis and thrombolysis}, volume = {}, number = {}, pages = {}, pmid = {39891865}, issn = {1573-742X}, support = {82104638//National Natural Science Foundation of China/ ; 82260924//National Natural Science Foundation of China/ ; 82274374//National Natural Science Foundation of China/ ; 824MS068//Natural Science Foundation of Hainan Province/ ; }, abstract = {Chronic thromboembolic pulmonary hypertension (CTEPH) and COVID-19 share molecular pathways yet remain poorly understood in their interrelation. Using RNA-seq datasets (GSE130391 and GSE169687), we identified 645, 206, and 1,543 differentially expressed genes (DEGs) for long-COVID (16 and 24 weeks post-infection) and CTEPH, respectively. Weighted Gene Co-Expression Network Analysis (WGCNA) pinpointed 234 intersecting key module genes. Three hub genes-DNAJA1, NDUFA5, and SLC2A14-were identified with robust discriminatory capabilities (AUC ≥ 0.7). Enrichment analyses revealed shared pathways linked to immune modulation, oxidative stress, and metabolic dysfunction. Immune analysis highlighted activated CD8 T cells as critical regulators. Regulatory networks implicated TFs and miRNAs, including STAT1 and hsa-mir-23a-3p. Drug prediction identified potential therapeutic compounds with strong molecular docking interactions. These findings unravel critical molecular linkages, emphasizing shared pathogeneses and guiding experimental validations for improved diagnostic and therapeutic strategies in COVID-19 and CTEPH.}, } @article {pmid39891711, year = {2025}, author = {Berg, OK and Aagård, N and Helgerud, J and Brobakken, MF and Hoff, J and Wang, E}, title = {No impairment of maximal oxygen uptake, pulmonary function and walking economy in patients diagnosed with long COVID: consideration of disease severity.}, journal = {European journal of applied physiology}, volume = {}, number = {}, pages = {}, pmid = {39891711}, issn = {1439-6327}, } @article {pmid39890407, year = {2024}, author = {Lindbergh, CA and Altizer, R and Grady, JJ and Diniz, BS and Kamath, J and Steffens, DC and Morimoto, SS}, title = {Computerized cognitive remediation of Long COVID in older adults.}, journal = {International psychogeriatrics}, volume = {36}, number = {12}, pages = {1267-1269}, doi = {10.1017/S1041610224000139}, pmid = {39890407}, issn = {1741-203X}, } @article {pmid39890371, year = {2025}, author = {Marimuthu, Y and Nair, GC and Nagesh, U and Anand, A and Chopra, KK and Nagappa, B and Sharma, N and Sivashankar, G and Nagaraj, N}, title = {Prevalence of probable post-COVID cardiac sequelae and its health seeking behaviour among health care workers: A cross-sectional analytical study.}, journal = {The Indian journal of tuberculosis}, volume = {72}, number = {1}, pages = {5-11}, doi = {10.1016/j.ijtb.2023.06.008}, pmid = {39890371}, issn = {0019-5707}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; Cross-Sectional Studies ; Adult ; India/epidemiology ; *Health Personnel ; Prevalence ; *Patient Acceptance of Health Care/statistics & numerical data ; Middle Aged ; SARS-CoV-2 ; Young Adult ; Heart Diseases/epidemiology ; }, abstract = {BACKGROUND: Post-COVID Sequelae are considered as the signs and symptoms that develop during or after an infection consistent with COVID-19 which continue for more than 12 weeks and are not explained by alternative diagnosis. The prevalence of post-COVID cardiac sequelae ranges from 2% to 71% across the globe and it is reported to be around 22% in India. With this background, the study was conducted to assess the prevalence of probable post-COVID cardiac sequelae (PCCS) and delay in health-seeking for post-COVID cardiac sequelae among healthcare workers.

METHODS: A facility-based cross-sectional study was conducted among health workers and students in a medical educational institute in Karnataka from May 2022 to July 2022. Health workers and students who had a past history of COVID-19 during the COVID pandemic were included in the study. Socio-demographic details, clinical profile, symptoms of post-COVID cardiac sequelae, and health-seeking behavior were collected. Data were collected in Epicollect5 and analyzed using STATA statistical software. The prevalence of probable PCCS was expressed with 95% confidence interval. Univariate binomial logistic regression was done to assess the determinants of probable post-COVID sequelae.

RESULTS: A total of 336 health workers were included in the study with a mean (SD) age of 25.6 (8.6) years. A majority (68.2%) of them were females and only 25 (7.4%) belonged to the age group of 45-60 years. The prevalence of probable post-COVID cardiac sequelae among health workers and medical students was 11.9% (95% CI: 8.76-15.7). Among the 40 participants who had probable post-COVID cardiac sequelae, 55% (95% CI: 40%-70%) were not evaluated further which was their treatment-seeking behavior. Females, hypertensive individuals, and those who had moderate-severe disease during acute COVID-19 disease were at higher risk of developing probable post-COVID cardiac sequelae.

CONCLUSION: Around one out of ten individuals had experienced probable post-COVID cardiac sequelae, but only half of them got evaluated for it. An appropriate screening program for post-COVID cardiac sequelae needs to be implemented along with awareness-raising activities about long COVID to prevent the morbidity and mortality associated with it.}, } @article {pmid39890144, year = {2025}, author = {Pogreba Brown, K and Austhof, E and McFadden, CM and Scranton, C and Sun, X and Vujkovic-Cviji, I and Rodriguez, D and Falk, L and Heslin, KM and Arani, G and Obergh, V and Bessey, K and Cooper, K}, title = {Determining the incidence, risk factors and biological drivers of irritable bowel syndrome (IBS) as part of the constellation of postacute sequelae of SARS-CoV-2 infection (PASC) outcomes in the Arizona CoVHORT-GI: a longitudinal cohort study.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e095093}, doi = {10.1136/bmjopen-2024-095093}, pmid = {39890144}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; *Irritable Bowel Syndrome/epidemiology ; Longitudinal Studies ; Arizona/epidemiology ; *Post-Acute COVID-19 Syndrome ; Incidence ; Risk Factors ; *SARS-CoV-2 ; Male ; Female ; Biomarkers/blood ; Adult ; Middle Aged ; Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Postacute sequelae of SARS-CoV-2 infection (PASC) are extensive. Also known as long COVID, primary outcomes reported are neurologic, cardiac and respiratory in nature. However, several studies have also reported an increase in gastrointestinal (GI) symptoms and syndromes following COVID-19. This study of PASC will include extensive analyses of GI symptoms, determine if people with pre-existing irritable bowel syndrome (IBS) are at higher risk of developing PASC generally or PASC-GI, and which biomarkers are impacted and to what degree. This R01 study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK135483-01) from 2023 to 2028.

METHODS AND ANALYSES: This study combines a longitudinal epidemiologic cohort study and in-depth, novel biologic analyses. In collaboration with a pre-existing study, the Arizona CoVID-19 Cohort (CoVHORT)-GI will recruit participants based on the history of COVID infection(s), new or ongoing GI symptoms 3-6 months postinfection, and pre-existing or incident IBS diagnosis to represent five study groups for comparison and analyses. A subset (n=1000) of those recruited will submit both stool and blood samples. Both samples will undergo a novel method to quantitate humoral and mucosal immune responses to host-derived faecal communities in conjunction with magnetic bead-based separation and high-depth shotgun microbial sequencing. Stool samples will also undergo traditional microbiome analyses (diversity and abundance) and faecal calprotectin assays. Additional serum analyses will aim to determine if a proteomics-based signature exists that differentiates a unique biomarker compositional signature discriminating PASC-GI versus no PASC. All laboratory data will be linked with in-depth epidemiologic data on demographics, symptoms and chronic conditions.

ETHICS AND DISSEMINATION: This study involves human participants and was approved by the University of Arizona Institutional Review Board (IRB (#00002332) and has been deemed minimal risk. Participants gave informed consent to participate in the study before taking part. All publications from the study will be shared back to participants along with alternative lay summaries and webinars to communicate key findings. The data management plan has been published and is publicly available online, including protocols for data requests.}, } @article {pmid39889481, year = {2025}, author = {Saha, A and Choudhary, S and Walia, P and Kumar, P and Tomar, S}, title = {Transformative approaches in SARS-CoV-2 management: Vaccines, therapeutics and future direction.}, journal = {Virology}, volume = {604}, number = {}, pages = {110394}, doi = {10.1016/j.virol.2025.110394}, pmid = {39889481}, issn = {1096-0341}, abstract = {The global healthcare and economic challenges caused by the pandemic of COVID-19 reinforced the urgent demand for quick and effective therapeutic and preventative interventions. While vaccines served as the frontline of defense, antivirals emerged as adjunctive countermeasures, especially for people who developed infection, were immunocompromised, or were reluctant to be vaccinated. Beyond the serious complications of SARS-CoV-2 infection, the threats of long-COVID and the potential for zoonotic spillover continue to be significant health concerns that cannot be overlooked. Moreover, the incessant viral evolution, clinical safety issues, waning immune responses, and the emergence of drug-resistant variants pinpoint towards more severe viral threats in the future and call for broad-spectrum innovative therapies as a pre-pandemic preparedness measure. The present review provides a comprehensive up-to-date overview of the strategies utilized in the development of classical and next-generation vaccines against SARS-CoV-2, the clinical and experimental data obtained from clinical trials, while addressing safety risks that may arise. Besides vaccines, the review also covers recent breakthroughs in anti-SARS-CoV-2 drug discovery, emphasizing druggable viral and host targets, virus- and host-targeting antivirals, and highlighting mechanistically representative molecules that are either approved or are under clinical investigation. In conclusion, the integration of both vaccines and antiviral therapies, along with swift innovative strategies to address viral evolution and drug resistance is crucial to strengthen our preparedness against future viral outbreaks.}, } @article {pmid39888873, year = {2025}, author = {Vasconcelos, DSS and Pompeo, DA and Antonio-Viegas, MCR and Miasso, AI and Arruda, GO and Teston, EF and Saraiva, EF and Giacon-Arruda, BCC}, title = {Factors associated with long Covid in nursing professionals.}, journal = {Revista da Escola de Enfermagem da U S P}, volume = {58}, number = {}, pages = {e20240268}, doi = {10.1590/1980-220X-REEUSP-2024-0268en}, pmid = {39888873}, issn = {1980-220X}, mesh = {Humans ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Male ; Female ; Adult ; Middle Aged ; Prevalence ; Post-Acute COVID-19 Syndrome ; Resilience, Psychological ; Life Style ; Mental Health ; Sex Factors ; Young Adult ; }, abstract = {OBJECTIVE: To analyze the association between sociodemographic variables, lifestyle and mental health habits, and long Covid in nursing professionals.

METHOD: Quantitative, observational, cross-sectional and analytical study, with 109 nursing professionals who had Covid-19 between 2020 and 2022. Data collection was carried out using an online form, with the following variables of interest: resilience, subjective well-being, age, sex, professional category, vaccination, physical activity, presence of symptoms resulting from Covid-19 infection after the acute phase of the disease and long Covid. Data were analyzed descriptively and inferentially using Poisson regression with robust variance and a significance level of 5%.

RESULTS: Male sex, high resilience, and high positive affect decrease the prevalence of long Covid by 71% (RP = 0.29), 40% (RP = 0.60) and 43% (RP = 0.57), respectively, while being in the nursing technician category increases its prevalence by 74% (RP = 1.74).

CONCLUSION: The results emphasize the importance and support the development of promotion, prevention, treatment, and rehabilitation actions for individuals with long Covid. To achieve this, multidisciplinary care, centered on the person and directed at the context and work environment is required.}, } @article {pmid39888379, year = {2025}, author = {Braun, J}, title = {[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long COVID?-Part 2].}, journal = {Zeitschrift fur Rheumatologie}, volume = {}, number = {}, pages = {}, pmid = {39888379}, issn = {1435-1250}, abstract = {Acute and chronic pain play an important part in the care of patients with musculoskeletal diseases. For rheumatologists this represents a frequent challenge. For the management of chronic pain conditions in rheumatology those that cannot be explained by objective tissue damage are particularly important-which makes patients' subjective assessment of pain a central building block of the diagnosis. For the diagnosis of fibromyalgia (FM) standardized questionnaires such as the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS) are used. In connection with the recent global SARS-CoV‑2 pandemic protracted courses and health problems have been described, which have been termed long COVID syndrome and have some similarities but, as is shown in the following, also demonstrate some differences from FM. There has recently been an interesting scientific controversy that culminated in a pros and cons session at the EULAR congress 2024, following several publications. The arguments and citations exchanged have served as the basis for the overview produced here, which is intended to offer rheumatologists confronted with such clinical pictures assistance with the assessment of these diseases, even if the results of the studies presented are definitely controversial.}, } @article {pmid39888378, year = {2025}, author = {Braun, J}, title = {[Chronic pain syndrome in musculoskeletal diseases-how different are fibromyalgia and long Covid?-Part 1].}, journal = {Zeitschrift fur Rheumatologie}, volume = {}, number = {}, pages = {}, pmid = {39888378}, issn = {1435-1250}, abstract = {Chronic pain is a common problem in rheumatology. Nociceptive pain is distinguished from neuropathic and nociplastic pain. Mechanistically, the former is explained by persistent inflammation, for example. Included in the second category is nerve damage of various causes. In contrast, nociplastic pain is not caused by tissue damage or a lesion in the somatosensory nerve system. It is caused by an altered sensation of pain through the modulation of stimulus processing. The concept of central sensitization, together with further neurobiological and psychosocial mechanisms, best explains such pain conditions. Fibromyalgia (FM) plays a big part in rheumatology - on the one hand, as a differential diagnosis, and on the other, because the management of inflammatory rheumatic conditions is made more difficult by the simultaneous occurrence of FM. In the context of the coronavirus pandemic, persistent pain syndromes with similarities to FM have been described after COVID-19 infection. There is an increasing scientific controversy whether the so-called long Covid syndrome is an actual entity or "only" a variant of FM. This discussion and the current state of knowledge on the problem are the subject of this review.}, } @article {pmid39886482, year = {2025}, author = {Han, Y and Dai, Y and Wang, K and Zhang, X and Shao, Z and Zhu, X}, title = {Post-pandemic insights on COVID-19 and premature ovarian insufficiency.}, journal = {Open life sciences}, volume = {20}, number = {1}, pages = {20221028}, doi = {10.1515/biol-2022-1028}, pmid = {39886482}, issn = {2391-5412}, abstract = {The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection's inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as "long COVID," may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19's impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.}, } @article {pmid39885244, year = {2025}, author = {Prazanowska, KH and Kim, TH and Kang, JW and Jin, YH and Kwon, S and Lim, SB}, title = {A single-cell RNA sequencing dataset of peripheral blood cells in long COVID patients on herbal therapy.}, journal = {Scientific data}, volume = {12}, number = {1}, pages = {177}, pmid = {39885244}, issn = {2052-4463}, support = {2020R1A6A1A03043539//National Research Foundation of Korea (NRF)/ ; 2022R1C1C1004756//National Research Foundation of Korea (NRF)/ ; 2020M3A9D8037604//National Research Foundation of Korea (NRF)/ ; 2020R1A6A1A03043539//National Research Foundation of Korea (NRF)/ ; 2020M3A9D8037604//National Research Foundation of Korea (NRF)/ ; 2022R1C1C1004756//National Research Foundation of Korea (NRF)/ ; HR22C1734//Korea Health Industry Development Institute (KHIDI)/ ; HR22C1734//Korea Health Industry Development Institute (KHIDI)/ ; KSN2121220//Korea Institute of Oriental Medicine (KIOM)/ ; KSN2121220//Korea Institute of Oriental Medicine (KIOM)/ ; }, abstract = {Following the coronavirus disease 2019 (COVID-19) pandemic, the rise of long COVID, characterized by persistent respiratory and cognitive dysfunctions, has become a significant health concern. This leads to an increased role of complementary and alternative medicine in addressing this condition. However, our comprehension of the effectiveness and safety of herbal medicines for long COVID remains limited. Here, we present a single-cell RNA sequencing (scRNA-seq) dataset of peripheral whole blood cells derived from participants in a clinical study involving three commercially available herbal medicines, targeting fatigue and brain fog in long COVID. The dataset comprises 181,205 quality control (QC)-passed cells, along with clinical metadata, enabling a comparative analysis of immune cell populations before and after treatment. To ensure the technical validity of our dataset, we implemented rigorous quality checks throughout stages of the study, including sample preparation, sequencing, and bioinformatic data analysis levels. This transcriptomic data may serve as a resource to deepen our insights into the role of herbal medicines in management of long COVID.}, } @article {pmid39884720, year = {2025}, author = {Terry, P and Heidel, RE and Wilson, AQ and Dhand, R}, title = {Risk of long covid in patients with pre-existing chronic respiratory diseases: a systematic review and meta-analysis.}, journal = {BMJ open respiratory research}, volume = {12}, number = {1}, pages = {}, doi = {10.1136/bmjresp-2024-002528}, pmid = {39884720}, issn = {2052-4439}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Asthma/epidemiology/complications ; *Pulmonary Disease, Chronic Obstructive/epidemiology/complications ; *SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: An estimated 10-30% of people with COVID-19 experience debilitating long-term symptoms or long covid. Underlying health conditions associated with chronic inflammation may increase the risk of long covid.

METHODS: We conducted a systematic review and meta-analysis to examine whether long covid risk was altered by pre-existing asthma or chronic obstructive pulmonary disease (COPD) in adults. We identified studies by searching the PubMed and Embase databases from inception to 13 September 2024. We excluded studies that focused on children or defined long covid only in terms of respiratory symptoms. We used random-effects, restricted maximum likelihood models to analyse data pooled from 51 studies, which included 43 analyses of asthma and 30 analyses of COPD. The risk of bias was assessed using a ROBINS-E table.

RESULTS: We found 41% increased odds of long covid with pre-existing asthma (95% CI 1.29 to 1.54); pre-existing COPD was associated with 32% increased odds (95% CI 1.16 to 1.51). Pre-existing asthma, but not COPD, was associated with increased odds of long covid-associated fatigue. We observed heterogeneity in the results of studies of asthma related to hospitalisation status. Potential confounding and inconsistent measurement of exposure and outcome variables were among the identified limitations.

CONCLUSIONS: Our findings support the hypothesis that pre-existing asthma and COPD increase the risk of long covid, including chronic fatigue outcomes in patients with asthma. Because COVID-19 targets the respiratory tract, these inflammatory conditions of the lower respiratory tract could provide mechanistic clues to a common pathway for the development of long-term sequelae in patients with long covid.}, } @article {pmid39884431, year = {2025}, author = {Shimba, R and Hanai, S and Ito, R and Tanaka-Mabuchi, N and Maejima, Y and Harai, N and Tsuchiya, K and Nakagomi, D}, title = {Isolated adrenocorticotropic hormone deficiency manifested after COVID-19.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {}, number = {}, pages = {102635}, doi = {10.1016/j.jiac.2025.102635}, pmid = {39884431}, issn = {1437-7780}, abstract = {Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 and long COVID can present with nonspecific symptoms resembling adrenal insufficiency. This similarity of symptoms means that adrenal insufficiency hidden among nonspecific manifestations of COVID-19 may pass underrecognized. We present the case of a 53-year-old Japanese man who developed isolated adrenocorticotrophic hormone (ACTH) deficiency (IAD) and acute adrenal insufficiency after COVID-19, thus mimicking prolonged symptoms of COVID-19. The patient developed fever, cough, and sore throat and was diagnosed with COVID-19. After anti-viral treatment, fever, loss of appetite, and general fatigue persisted, and hyponatremia was observed. Endocrinological testing on admission showed baseline concentrations of 3.5 μg/dL for cortisol and <1.5 pg/mL for ACTH. No abnormalities of other pituitary hormones were evident. Standard ACTH stimulation tests showed a decreased peak serum cortisol concentration and corticotropin-releasing hormone stimulation tests revealed no ACTH secretory response. Magnetic resonance imaging of the pituitary revealed no abnormalities. Adrenal insufficiency due to IAD was diagnosed based on the results of endocrinological testing. Intravenous and oral hydrocortisone improved symptoms and hyponatremia. The patient has experienced no recurrence of adrenal insufficiency under hydrocortisone treatment. COVID-19 can mimic adrenal insufficiency. IAD should be considered when nonspecific symptoms persist after treatment for COVID-19.}, } @article {pmid39883551, year = {2025}, author = {Wilkins, D and Tapley, A and Dizon, J and Holliday, E and Davey, A and Fielding, A and Moad, D and van Driel, M and Ralston, A and Fisher, K and Magin, P and Stocks, N}, title = {General practice registrar evaluation of long COVID in patients presenting with fatigue.}, journal = {Australian journal of primary health}, volume = {31}, number = {}, pages = {}, doi = {10.1071/PY24163}, pmid = {39883551}, issn = {1836-7399}, mesh = {Humans ; *COVID-19/complications/diagnosis/epidemiology ; *Fatigue/diagnosis ; Male ; Female ; Middle Aged ; Adult ; General Practice/methods ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Australia/epidemiology ; Cohort Studies ; Diagnosis, Differential ; General Practitioners ; Aged ; }, abstract = {Background Long COVID is a new and prevalent condition defined by persistent symptoms following acute COVID-19 infection. While increasing resources are being directed to management, there is little evidence on how general practitioners (GPs) have changed their assessment and differential diagnosis of patients with potential long COVID symptoms including fatigue. This study aimed to examine how often GP registrars consider long COVID in patients presenting with fatigue, how often they think long COVID might be the cause for fatigue, and patient, registrar, practice, and consultation factors associated with these outcomes. Methods Data were collected through Registrar Clinical Encounters in Training (ReCEnT), an ongoing inception cohort study of GP registrars' in-consultation experiences, during two collection rounds in 2022-2023. Multivariable logistic regression was used to examine the relationship between predictor variables and outcomes. Results A total of 969 registrars recorded 3193 consultations where fatigue was a symptom. Registrars reported considering long COVID as a differential diagnosis in 2563 encounters (80%, 95% confidence interval (CI) 79-82%). Of these, registrars thought long COVID was the likely cause for fatigue in 465 encounters (18%, 95% CI 17-20%). While no patient variables were significantly associated with either outcome, multivariable associations included telehealth consultations having greater odds of both outcomes and Australian-trained registrars having lesser odds of considering long COVID likely. Conclusions Registrars report usually considering long COVID as a differential for fatigue and frequently considering it a likely diagnosis. Telehealth usage was significantly associated with both outcomes. Future work should explore GPs' diagnostic approaches to other potential long COVID symptoms.}, } @article {pmid39882499, year = {2025}, author = {Smith, AB and Greenwood, DC and Williams, P and Kwon, J and Petrou, S and Horton, M and Osborne, T and Milne, R and Sivan, M and , }, title = {Health-Related Quality of Life in Long COVID: Mapping the Condition-Specific C19-YRSm Measure Onto the EQ-5D-5L.}, journal = {Patient related outcome measures}, volume = {16}, number = {}, pages = {55-66}, pmid = {39882499}, issn = {1179-271X}, abstract = {BACKGROUND: Long COVID (LC) is a clinical syndrome with persistent, fluctuating symptoms subsequent to COVID-19 infection. LC has significant detrimental effects on health-related quality of life (HRQoL), activities of daily living (ADL), and work productivity. Condition-specific patient-reported outcome measures (PROMs), such as the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) do not provide the health utility data required for cost-utility analyses of LC interventions. The aim of this study was to derive a mapping algorithm for the C19-YRSm to enable health utilities to be generated from this PROM.

METHODS: Data were collected from a large study evaluating LC services in the UK. A total of 1434 people with LC had completed both the C19-YRSm and the EQ-5D. Correlation and linear regression analyses were applied to determine items from the C19-YRSm and covariates for inclusion in the algorithm. Model fit, mean differences across the range of EQ-5D-3L utility scores, and Bland-Altman plots were evaluated. Responsiveness (standardised response mean; SRM) of the mapped utilities was investigated on a subset of participants with repeat assessments.

RESULTS: There was a strong level of association between 8 items and one domain on the C19-YRSm with the EQ-5D single-item dimensions. Model fit was good (R[2] = 0.7). The mean difference between observed and mapped scores was <0.10 for the range from 0 to 1 indicating good targeting for positive values of the EQ-5D-3L. The SRM for the mapped EQ-5D-3L was 0.37 compared to 0.17 for the observed utility scores, suggesting the mapped EQ-5D-3L is more responsive to change.

CONCLUSION: A simple, responsive, and robust mapping algorithm was developed to generate enable EQ-5D-3L health utilities from the C19-YRSm. This will facilitate economic evaluations of LC interventions, treatment, and management, as well as further helping to describe and characterise patients with LC irrespective of any treatment and interventions.}, } @article {pmid39882453, year = {2024}, author = {Xu, H and Lu, T and Liu, Y and Yang, J and Ren, S and Han, B and Lai, H and Ge, L and Liu, J}, title = {Prevalence and risk factors for long COVID among cancer patients: a systematic review and meta-analysis.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1506366}, pmid = {39882453}, issn = {2234-943X}, abstract = {OBJECTIVE: The prevalence of long COVID among cancer patients remains unknown. This study aimed to determine the prevalence of long COVID and explore potential risk factors among cancer patients.

METHODS: A systematic search was performed on PubMed, Web of Science, and Embase from database inception until 21 March 2024, to identify studies that reported long COVID in cancer patients. Two investigators independently screened the studies and extracted all information about long COVID in cancer patients for subsequent analysis. Methodological quality was assessed using the "Joannagen Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data".

RESULTS: A total of 13 studies involving 6,653 patients were included. The pooled prevalence of long COVID was 23.52% [95% confidence interval (CI), 12.14% to 40.64%] among cancer patients reported experiencing long COVID after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The pooled prevalence of any long COVID in cancer patients was 20.51% (95% CI, 15.91% to 26.03%), 15.79% (95% CI, 11.39% to 21.47%), and 12.54% (95% CI, 6.38% to 23.18%) in 3, 6, and 12 months follow-up duration. Fatigue was the most common symptom, followed by respiratory symptoms, myalgia, and sleep disturbance. Patients with comorbidities had a significantly higher risk of experiencing long COVID [odds ratio (OR) = 1.72; 95% CI, 1.09 to 2.70; p = 0.019]. No statistically significant differences in sex, primary tumor, or tumor stage were detected.

CONCLUSION: Nearly a quarter of cancer patients will experience long COVID after surviving from SARS-CoV-2 infection, and this would even last for 1 year or longer. Fatigue, respiratory symptoms, myalgia, and sleep disturbance need to be more addressed and managed to reduce symptom burden on cancer patients and improve quality of life. Patients with comorbidities are at a high risk of developing long COVID. Further randomized controlled trials with rigorous methodological designs and large sample sizes are needed for future validation.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023456665.}, } @article {pmid39882369, year = {2024}, author = {Pierson, BC and Apilado, K and Franzos, MA and Allard, R and Mancuso, JD and Tribble, D and Saunders, D and Koehlmoos, TP}, title = {Oral medications for the treatment of postural orthostatic tachycardia syndrome; a systematic review of studies before and during the COVID-19 pandemic.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1515486}, pmid = {39882369}, issn = {1664-2295}, abstract = {BACKGROUND: Postural Orthostatic Tachycardia Syndrome (POTS) is a complex form of dysautonomia that presents with abnormal autonomic reflexes upon standing, leading to symptoms such as lightheadedness, tachycardia, fatigue, and cognitive impairment. The COVID-19 pandemic has brought renewed attention to POTS due to its overlap with post-acute sequelae of COVID-19 (PASC). Studies have found that a substantial percentage of COVID-19 survivors exhibit symptoms resembling POTS, elevating POTS diagnoses to previously unseen levels. We systematically reviewed the literature for existing high-quality evidence on potential interventions.

METHODS: A systematic review of the literature was performed to identify studies of oral medications for the management of POTS. We searched for published manuscripts on the medical management of POTS through 6 April 2024 which met pre-specified inclusion criteria. We conducted quality appraisal and assessed risk of bias before extracting the data and performing synthesis to determine the current state of the evidence; particularly in the context of PASC.

RESULTS: The study search and selection process identified 32 studies that met inclusion criteria, comprising randomized controlled trials, observational studies, and systematic reviews. Most included studies were judged to be of moderate to high quality, with largely low risk of bias. The most frequently studied medications were beta-blockers, ivabradine, and midodrine. Ivabradine and midodrine demonstrated the highest rate of symptomatic improvement, while beta-blockers showed the largest reduction in heart rate variability. Limited evidence was available for PASC-associated POTS, but findings suggest that treatments may have similar efficacy in both PASC and non-PASC cases.

CONCLUSION: Ivabradine, midodrine, and beta-blockers currently appear to be reasonable front-line choices in pharmacologic management of POTS (PASC associated and otherwise). Further RCTs that evaluate long term outcomes of medications are needed to further establish evidence based pharmacologic treatment approaches for POTS. Particular areas of inquiry include differential efficacy of recommended therapies based on POTS subtypes, and a need for treatments directly targeting the underlying autonomic nervous system dysfunction.

PROSPERO, identifier CRD42024505967, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=505967.}, } @article {pmid39882367, year = {2024}, author = {Li, Y and Liu, M and Zhang, R and Wang, Y and Liu, J}, title = {Long COVID-19-related and non-COVID-19 postviral olfactory dysfunction a comparative MRI study focusing on the olfactory cleft and bulbs.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1535699}, pmid = {39882367}, issn = {1664-2295}, abstract = {OBJECTIVE: To compare the magnetic resonance imaging (MRI) features of the olfactory cleft (OC) and olfactory bulbs (OBs) in patients with long COVID-19-related (LCOD) and non-COVID-19 postviral olfactory dysfunction (NCPVOD) to explore mechanisms underlying persistent olfactory dysfunction.

METHODS: This retrospective analysis included patients diagnosed with LCOD or NCPVOD at the China-Japan Friendship Hospital between February 2023 and July 2024. All patients underwent olfactory psychophysical testing (Sniffin' Sticks), a visual analogue scale (VAS) for olfactory function, and high-resolution MRI scans of the olfactory pathway. MRI features, including OC opacity, OB morphology, OB volume, and olfactory sulcus depth, were compared between groups. Correlations between MRI findings and olfactory test scores were assessed.

RESULTS: Seventy patients were included (35 LCOD, 35 NCPVOD). LCOD patients had significantly higher OC opacity scores than NCPVOD patients (p < 0.001). No significant differences were found in OB morphology, abnormal OB signals, OB volume reduction, or distances between OBs and surrounding structures (p > 0.05). LCOD patients had significantly greater right olfactory sulcus depth than NCPVOD patients (p = 0.026), with negative correlation to age (r = -0.25, p = 0.04). OB volumes positively correlated with TDI and VAS scores.

CONCLUSION: LCOD patients exhibited greater OC opacity than NCPVOD patients, suggesting OC inflammation may contribute to persistent olfactory dysfunction. Treating inflammation in the OC could improve long-term olfactory outcomes. OB volume reduction was common in both groups.}, } @article {pmid39881669, year = {2024}, author = {Al-Aly, Z}, title = {Long Covid is a significant health crisis in China too.}, journal = {The Lancet regional health. Western Pacific}, volume = {52}, number = {}, pages = {101223}, pmid = {39881669}, issn = {2666-6065}, } @article {pmid39881668, year = {2024}, author = {Qin, S and Zhang, Y and Li, Y and Huang, L and Yang, T and Si, J and Wang, L and Zhao, X and Ma, X and Gao, GF}, title = {Long COVID facts and findings: a large-scale online survey in 74,075 Chinese participants.}, journal = {The Lancet regional health. Western Pacific}, volume = {52}, number = {}, pages = {101218}, pmid = {39881668}, issn = {2666-6065}, abstract = {BACKGROUND: Research on long COVID in China is limited, particularly in terms of large-sample epidemiological data and the effects of recent SARS-CoV-2 sub-variants. China provides an ideal study environment owing to its large infection base, high vaccine coverage, and stringent pre-pandemic measures.

METHODS: This retrospective study used an online questionnaire to investigate SARS-CoV-2 infection status and long COVID symptoms among 74,075 Chinese residents over one year. The relationships between baseline characteristics, vaccination status, pathogenic infection, and long COVID were analyzed using multinomial logistic regression, and propensity matching.

FINDINGS: Analysis of 68,200 valid responses revealed that the most frequent long COVID symptoms include fatigue (30.53%), memory decline (27.93%), decreased exercise ability (18.29%), and brain fog (16.87%). These symptoms were less prevalent among those infected only once: fatigue (24.85%), memory decline (18.11%), and decreased exercise ability (12.52%), etc. Women were more likely to experience long COVID, with symptoms varying by age group, except for sleep disorders and muscle/joint pain, which were more common in older individuals. Northern China exhibits a higher prevalence of long COVID, potentially linked to temperature gradients. Risk factors included underlying diseases, alcohol consumption, smoking, and the severity of acute infection (OR > 1, FDR < 0.05). Reinfection was associated with milder symptoms but led to a higher incidence and severity of long COVID (OR > 1, FDR < 0.05). Vaccination, particularly multiple boosters, significantly reduced long-term symptoms by 30%-70% (OR < 1, FDR < 0.05). COVID-19 participants also self-reported more bacterial, influenza and mycoplasma infections, and 8%-10% of patients felt SARS-CoV-2-induced chronic diseases.

INTERPRETATION: This survey provides valuable insights into long COVID situation among Chinese residents, with 10%-30% (including repeated infection) reporting symptoms. Monitoring at-risk individuals based on identified risk factors is essential for public health efforts.

FUNDING: This study was funded by the China Postdoctoral Science Foundation (2022M723344, 2023M743729), Guangdong Basic and Applied Basic Research Foundation (2023A1515110489), and the Bill & Melinda Gates Foundation (INV-027420).}, } @article {pmid39880461, year = {2025}, author = {Seers, K and Nichols, VP and Bruce, J and Ennis, S and Heine, P and Patel, S and Sandhu, HK and Underwood, M and McGregor, G and , and , }, title = {Qualitative evaluation of the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) randomised controlled trial (RCT): 'you are not alone'.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e085950}, doi = {10.1136/bmjopen-2024-085950}, pmid = {39880461}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/psychology/rehabilitation ; Male ; Female ; Middle Aged ; *Qualitative Research ; *Exercise Therapy/methods ; Adult ; *SARS-CoV-2 ; England ; Aged ; Wales ; Social Support ; }, abstract = {BACKGROUND: This qualitative evaluation was embedded in the Rehabilitation Exercise and psycholoGical support After COVID-19 InfectioN (REGAIN) study, a randomised controlled trial (RCT) for those with post-COVID-19 condition ('long COVID') after hospital admission for COVID-19, comparing weekly home-based, live online supervised group exercise and psychological support sessions with 'best practice usual care' (a single session of advice).

OBJECTIVE: To increase our understanding of how and why the REGAIN programme might have worked and what helped or hindered this intervention.

DESIGN: A qualitative evaluation which utilised interviews with participants and practitioners delivering the intervention. Framework and thematic analysis were used to analyse the findings.

SETTING: England and Wales, UK.

PARTICIPANTS: Adults discharged from National Health Service (NHS) hospitals at least 3 months previously after COVID-19, with ongoing physical and/or mental health sequelae.

RESULTS: Twenty intervention participants, 20 control participants and five practitioners were interviewed.The themes from the group support sessions were: (1) you are not alone; (2) sharing experiences and addressing worries; (3) gaining new perspectives; (4) hope for progression; (5) peer support and bonding; (6) integration of facilitation skills; (7) modified activity pacing and goal setting, and (8) giving participants structure. The themes from group exercise were: (1) monitoring and modification of the online exercise; (2) catering for differing abilities; (3) feeling safe and confident to exercise; (4) progression of fitness; (5) optimal timing in the recovery trajectory; (6) group effect; (7) initial apprehension about exercise group; (8) gauging exercise capabilities; (9) translating exercises into life; and (10) on-demand supplementary videos. The 1:1 consultation sessions revealed patients needed to tell their stories.

CONCLUSION: Being listened to and being understood by someone 'who got it' was very important to people with post-COVID-19 condition. The group sessions of both exercise and psychological support were valued by participants, working together, and learning from each other in the face of a new disease within a global pandemic.}, } @article {pmid39879449, year = {2025}, author = {Andrade, RL and Braga, LCA and Reis, RS and Santos, FSD and Jesus, NR and Cruz Neto, J and Almeida, ÉS and Muniz, VO and Sousa, AR}, title = {[How did men report their long COVID experience? Health-Disease socio-anthropological meaning].}, journal = {Ciencia & saude coletiva}, volume = {30}, number = {1}, pages = {e05682023}, doi = {10.1590/1413-81232025301.05682023}, pmid = {39879449}, issn = {1678-4561}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Brazil/epidemiology ; Middle Aged ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Masculinity ; Qualitative Research ; }, abstract = {The study aims to explain the discourse of the collective subject of adult and elderly men about the experience of long COVID. Qualitative research, derived from a national multicenter clinical-virtual observatory involving 92 adult men, between 2022 and 2023 in Brazil. IRaMuTeQ software was used (data processing), the Collective Subject Discourse technique (analysis) and socio-anthropological references of the disease experience (interpretation). The results showed that the long COVID experience was marked by the prolongation of respiratory symptoms characteristic of COVID-19; systemic symptomatology in the physical-psychic body; and severe clinical complications. The experience of the long COVID-19 disease was shaped by gender relations and masculinities, constructed notions of health-disease, imaginaries about the capacity of the disease in the context of vaccination, the systemic character of syndromic events understood as sequelae left by the disease, resonating the sense of incapacity and stigmatization.}, } @article {pmid39878862, year = {2025}, author = {DeMars, J and Durand-Moreau, Q and Branton, E and Nowrouzi-Kia, B and Gross, DP and , }, title = {Improving Occupational Rehabilitation for People Living with Long COVID.}, journal = {Journal of occupational rehabilitation}, volume = {}, number = {}, pages = {}, pmid = {39878862}, issn = {1573-3688}, } @article {pmid39877136, year = {2025}, author = {Yousaf, R and Sultan, T}, title = {Experiences of south Asian key workers in COVID-19 lockdowns in the United Kingdom.}, journal = {Journal of migration and health}, volume = {11}, number = {}, pages = {100300}, pmid = {39877136}, issn = {2666-6235}, abstract = {BACKGROUND: This study aims to explore the experiences, challenges, and support given to South Asian Key Workers (food and necessary goods, Transport (delivery and taxi drivers,) working in the United Kingdom in times of the COVID-19 lockdowns between March 2020 to March 2021. The qualitative study aims to explore the experiences, challenges, and financial support given to South Asian Key Workers working in the United Kingdom in times of the COVID-19 lockdowns.

METHODS: A phenomenological approach was used to explore the experiences of key workers during the COVID-19 lockdowns in the UK. Snowball sampling was used to contact participants, who were South Asian key workers working in food, necessary goods and transport during COVID-19 lockdown in United Kingdom. Semi-structured, in-depth face to face and telephonic interviews were conducted with study participants in February and March 2021. Inductive qualitative approach was used for data analysis, and data analysis was done parallel with data collection.

RESULTS: Researcher interviewed 17 key workers. During the data analysis four theme categories emerged: 1) Precarious working conditions, 2) Coping with stress and fear, 3) Sustainability pressures, and 4) Insufficient support. Overall, the results show that the many participants had been working in close interaction with co-workers, customers and clients, poor protective measures to prevent catching infection, excessive workload, received limited support from employer, no access to furlough pay, restriction based on immigration status and limited economic support. Instead, they had to use self-devised strategies to cope with the increased workload, economic burdens and protection from infection.

CONCLUSION: The precarious working conditions exhausted participants physically and economically. They were holding a lot of grievances and hurt inside due to long existing inequalities in the society, where many highly educated and skilled individuals were unable to get stable and secure employments, despite the health vulnerabilities, South Asian key workers worked through the Covid-19 lockdowns to overcome difficulties stem from precarious work. Although currently coping with increased debts, economic burdens and long COVID symptoms, comprehensive job security and entitlement to secure contracts with provisions to sick leaves and pays should be made available to address economic vulnerabilities of south Asian key workers.}, } @article {pmid39875996, year = {2025}, author = {Cederström, A and Mkoma, GF and Benfield, T and Agyemang, C and Nørredam, M and Rostila, M}, title = {Long COVID and its risk factors in migrants: a nationwide register study from Sweden.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {53}, pmid = {39875996}, issn = {1741-7015}, abstract = {BACKGROUND: Many studies have found more severe COVID-19 outcomes in migrants and ethnic minorities throughout the COVID-19 pandemic, while recent evidence also suggests higher risk of longer-term consequences. We studied the risk of a long COVID diagnosis among adult residents in Sweden, dependent on country of birth and accounting for known risk factors for long COVID.

METHODS: We used linked Swedish administrative registers between March 1, 2020 and April 1, 2023, to estimate the risk of a long COVID diagnosis in the adult population that had a confirmed COVID-19 infection. Poisson regressions were used to calculate incidence rate ratios (IRR) of long COVID by country/region of birth. The contribution of sex, preexisting health status, disease severity, vaccination status, and socioeconomic factors to differences in long COVID diagnosis by country/region of birth were further investigated.

RESULTS: Of the 1,869,188 persons diagnosed with COVID-19 that were included, 7539 had received a long COVID diagnosis. Compared with residents born in Sweden, we found higher risks of long COVID among migrants from East Europe (IRR: 1.44 CI: 1.29-1.60), Finland (IRR: 1.36 CI: 1.15-1.61), South Asia (IRR: 1.28 CI: 1.03-1.59), Other Asia (IRR: 1.35 CI: 1.13-1.62), Other Africa (IRR: 1.48 CI: 1.17-1.87), and the Middle East (IRR: 1.43 CI: 1.27-1.63) in models adjusted for age and sex. We discovered that disease severity, i.e., whether the person was hospitalized (IRR: 18.6 CI: 17.3-20.0) or treated in an intensive care unit (IRR: 120.5 CI: 111.7-129.8), primarily contributed to the higher risk of long COVID found in migrants while the contribution of vaccinations and social conditions were moderate. Preexisting health problems did not contribute to the increased risk of long COVID in migrants.

CONCLUSIONS: The greater exposure and impact of the COVID-19 virus among migrants also affected longer-term consequences. Disease severity was the most important risk factor for long COVID in migrants. The findings emphasize the need for targeted health interventions for migrant communities during an infectious disease pandemic, such as strategic vaccination campaigns and extending social insurance schemes, focusing on reducing disease severity to mitigate the longer-term health consequences of an infection.}, } @article {pmid39874576, year = {2025}, author = {Rojas, NK and Martin, S and Cortina-Borja, M and Shafran, R and Fox-Smith, L and Stephenson, T and Ching, BCF and d'Oelsnitz, A and Norris, T and Xu, Y and McOwat, K and Dalrymple, E and Heyman, I and Ford, T and Chalder, T and Simmons, R and , and Pinto Pereira, SM}, title = {Health and Experiences During the COVID-19 Pandemic Among Children and Young People: Analysis of Free-Text Responses From the Children and Young People With Long COVID Study.}, journal = {Journal of medical Internet research}, volume = {27}, number = {}, pages = {e63634}, doi = {10.2196/63634}, pmid = {39874576}, issn = {1438-8871}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Child ; Adolescent ; Female ; Male ; *Pandemics ; *Mental Health ; England/epidemiology ; SARS-CoV-2 ; Stress, Psychological/psychology/epidemiology ; Emotions ; Social Support ; }, abstract = {BACKGROUND: The literature is equivocal as to whether the predicted negative mental health impact of the COVID-19 pandemic came to fruition. Some quantitative studies report increased emotional problems and depression; others report improved mental health and well-being. Qualitative explorations reveal heterogeneity, with themes ranging from feelings of loss to growth and development.

OBJECTIVE: This study aims to analyze free-text responses from children and young people participating in the Children and Young People With Long COVID study to get a clearer understanding of how young people were feeling during the pandemic.

METHODS: A total of 8224 free-text responses from children and young people were analyzed using InfraNodus, an artificial intelligence-powered text network analysis tool, to determine the most prevalent topics. A random subsample of 411 (5%) of the 8224 responses underwent a manual sentiment analysis; this was reweighted to represent the general population of children and young people in England.

RESULTS: Experiences fell into 6 main overlapping topical clusters: school, examination stress, mental health, emotional impact of the pandemic, social and family support, and physical health (including COVID-19 symptoms). Sentiment analysis showed that statements were largely negative (314/411, 76.4%), with a small proportion being positive (57/411, 13.9%). Those reporting negative sentiment were mostly female (227/314, 72.3%), while those reporting positive sentiment were mostly older (170/314, 54.1%). There were significant observed associations between sentiment and COVID-19 status as well as sex (P=.001 and P<.001, respectively) such that the majority of the responses, regardless of COVID-19 status or sex, were negative; for example, 84.1% (227/270) of the responses from female individuals and 61.7% (87/141) of those from male individuals were negative. There were no observed associations between sentiment and all other examined demographics. The results were broadly similar when reweighted to the general population of children and young people in England: 78.52% (negative), 13.23% (positive), and 8.24% (neutral).

CONCLUSIONS: We used InfraNodus to analyze free-text responses from a large sample of children and young people. The majority of responses (314/411, 76.4%) were negative, and many of the children and young people reported experiencing distress across a range of domains related to school, social situations, and mental health. Our findings add to the literature, highlighting the importance of specific considerations for children and young people when responding to national emergencies.}, } @article {pmid39874315, year = {2025}, author = {Bidhendi-Yarandi, R and Biglarian, A and Karlstad, JL and Moe, CF and Bakhshi, E and Khodaei-Ardakani, MR and Behboudi-Gandevani, S}, title = {Prevalence of depression, anxiety, stress, and suicide tendency among individual with long-COVID and determinants: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0312351}, doi = {10.1371/journal.pone.0312351}, pmid = {39874315}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Depression/epidemiology ; *Anxiety/epidemiology ; Prevalence ; *Stress, Psychological/epidemiology ; Suicidal Ideation ; Risk Factors ; SARS-CoV-2 ; Suicide/psychology/statistics & numerical data ; Mental Health ; Female ; }, abstract = {BACKGROUND: While mental health alterations during active COVID-19 infection have been documented, the prevalence of long-term mental health consequences remains unclear. This study aimed to determine the prevalence of mental health symptoms-depression, anxiety, stress, and suicidal tendencies-and to identify their trends and associated risk factors in individuals with long-COVID.

METHODS: We conducted a systematic literature search of databases including PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, Web of Science, and PsycINFO up to August 2024, targeting observational studies published in English. Study quality was assessed using structured standard tools. The primary outcome was the pooled prevalence of depression, anxiety, stress, and suicidal tendencies in individuals with long-COVID. Secondary outcomes included trends in these mental health problems over time and identification of associated determinants.

RESULTS: A total of 94 eligible studies were included in the analysis. The pooled prevalence estimates, regardless of follow up times duration, were as follows: depression, 25% (95%CI:22-28%; PI:1-59%); anxiety (adjusted via trim and fill method), 23%(95%CI:21-25%;PI:2-35%); composite outcomes of depression and/or anxiety, 25% (95%CI:23-27%;PI:2-51%); stress, 26%(95%CI:13-39%;PI:1-69%); and suicidality, 19%(95%CI:15-22%;PI:13-25%). The results of meta-regression analyses revealed a statistically significant trend showing a gradual decrease in the prevalence of the composite outcome of anxiety and/or depression over time (RD = -0.004,P = 0.022). Meta-regression results indicated that being female and younger age were significantly associated with a higher prevalence of mental health symptoms. Study design and study setting did not contribute to heterogeneity.

CONCLUSION: One-fourth of individual with long-COVID experience mental health symptoms, including depression, anxiety, and stress, which remain prevalent even two years post-infection despite a slight decreasing trend. Factors such as female gender and younger age were linked to higher rates of anxiety and depression. These findings indicate the need for ongoing mental health screening and early interventions to mitigate long-term psychological distress in long-COVID patients.}, } @article {pmid39872302, year = {2023}, author = {Liang, X and Wang, Y and Guo, T}, title = {Proteomics approaches to long COVID: status and outlooks.}, journal = {Life medicine}, volume = {2}, number = {3}, pages = {lnad023}, pmid = {39872302}, issn = {2755-1733}, } @article {pmid39868023, year = {2024}, author = {Schäfer, LN and Rief, W}, title = {The influence of expectations on shame, rumination and cognitive flexibility: an experimental investigation on affect-regulatory characteristics of deceptive placebos.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1502460}, pmid = {39868023}, issn = {1664-1078}, abstract = {BACKGROUND: Several studies identified affect-regulatory qualities of deceptive placebos within negative and positive affect. However, which specific characteristics of an affect-regulatory framing impacts the placebo effect has not yet been subject to empirical investigations. In particular, it is unclear whether placebo- induced expectations of direct emotion inhibition or emotion regulation after emotion induction elicit stronger effects in affect regulation.

PURPOSE: The aim of the study was to identify whether specifically framed expectations on the occurrence (antecedent-focused) vs. regulation capability (response-modulating) of affect, induced with an active placebo nasal-spray, have effects on affect-regulatory processes. Because personality traits have been suspected to influence placebo responses and affect regulation, an additional goal of the study was to examine modulating influences of shame proneness, level of depression, experiential avoidance, and emotional control.

METHODS: Healthy volunteers (n = 121) were randomized to either a deceptive placebo condition (antecedent-focused vs. response-modulating instruction) or a no-treatment control group before shame was experimentally induced via autobiographical recall. Groups were compared on outcomes of state shame, rumination, and cognitive flexibility.

RESULTS: Both antecedent-focused and response-modulating placebo framings influenced changes in state shame (b = 3.08, 95% CI = [0.80-5.92], p = 0.044), rumination (b = 4.80, 95% CI = [1.50-8.09], p ≤ 0.001) and cognitive flexibility outcomes (b = -3.63, 95% CI = [-6.75 - -0.51], p = 0.011) after shame-induction interventions. Only the antecedent-focused placebo response was modulated by personality traits. Experiential avoidance modulated shame experience (F(2,115) = 3.470, p = 0.031) whereas emotional control influenced the reports of state rumination (F(2,115) = 4.588, p = 0.012). No modulatory influences of levels of depression and shame proneness could be observed (ps > 0.05).

CONCLUSION: The results suggest that shame, rumination and cognitive flexibility can be positively influenced by placebo treatment in healthy subjects. Personality traits of emotional control and experiential avoidance influenced the placebo response of the antecedent-focused treatment rationale on outcomes individually.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05372744.}, } @article {pmid39867374, year = {2024}, author = {Jamal, A and Dalhuisen, T and Gallego Márquez, N and Dziarski, AD and Uy, J and Walch, SN and Thomas, SA and Fehrman, EA and Romero, AE and Zelaya, AS and Akasreku, EA and Adeagbo, TV and Pasetes, EC and Akbas, SY and Azola, AM and Deeks, SG and Kelly, JD and Martin, JN and Henrich, TJ and Landay, AL and Peluso, MJ and Antar, AAR}, title = {Post-SARS-CoV-2 Onset Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms in Two Cohort Studies of COVID-19 Recovery.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.08.24316976}, pmid = {39867374}, abstract = {OBJECTIVE: To determine how many people with long COVID also meet diagnostic criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

METHODS: We identified which participants with long COVID also met the Institute of Medicine (IOM) or the 2003 Canadian Consensus Criteria (CCC) for ME/CFS at approximately 6-8 months post-SARS-CoV-2 infection in two cohorts: (1) the JHU COVID Recovery cohort, which enrolled participants within 4 weeks of infection and (2) the Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort, which enriched for participants with long COVID. Neither study administered ME/CFS-specific surveys, so available data elements were mapped onto each ME/CFS diagnostic criteria.

RESULTS: Of 97 JHU participants with long COVID, 5 met IOM criteria and 2 met CCC criteria. Of 281 LIINC participants with long COVID, 51 met the IOM criteria and 29 met the CCC criteria. In LIINC, participants with long COVID meeting ME/CFS criteria were more likely to be female and report a greater number of post-COVID symptoms (p<0.001).

CONCLUSIONS: The co-occurrence of ME/CFS symptoms and long COVID suggests that SARS-CoV-2 is a cause of ME/CFS. ME/CFS-specific measures should be incorporated into studies of post-acute COVID-19 to advance studies of post-SARS-CoV-2 onset ME/CFS.}, } @article {pmid39865778, year = {2025}, author = {Du, S and Jin, J and Tang, C and Su, Z and Wang, L and Chen, X and Zhang, M and Zhu, Y and Wang, J and Ju, C and Song, X and Li, S}, title = {Airway Basal Stem Cells Inflammatory Alterations in COVID-19 and Mitigation by Mesenchymal Stem Cells.}, journal = {Cell proliferation}, volume = {}, number = {}, pages = {e13812}, doi = {10.1111/cpr.13812}, pmid = {39865778}, issn = {1365-2184}, support = {2023B111105006//Guangdong Key Area R&D Program Key Project/ ; 82202222//National Natural Science Foundation of China/ ; 82203883//National Natural Science Foundation of China/ ; //Guangdong Special Support Plan Project : Shiyue Li declared that he had received the Guangdong Special Support Plan Project/ ; 2022A1515110508//GuangDong Basic and Applied Basic Research Foundation/ ; 2024A1515011593//GuangDong Basic and Applied Basic Research Foundation/ ; 2024A03J1143//Guangzhou Joint Projects of University/ ; 2025A03J4307//Guangzhou Joint Projects of University/ ; QT-2024-038//Young Talent Support Project of Guangzhou Association for Science and Technology/ ; 2023A04J0573//Guangzhou Fundamental and Basic Fundamental Projects/ ; 2025A04J3626//Guangzhou Fundamental and Basic Fundamental Projects/ ; }, abstract = {SARS-CoV-2 infection and the resultant COVID-19 pneumonia cause significant damage to the airway and lung epithelium. This damage manifests as mucus hypersecretion, pulmonary inflammation and fibrosis, which often lead to long-term complications collectively referred to as long COVID or post-acute sequelae of COVID-19 (PASC). The airway epithelium, as the first line of defence against respiratory pathogens, depends on airway basal stem cells (BSCs) for regeneration. Alterations in BSCs are associated with impaired epithelial repair and may contribute to the respiratory complications observed in PASC. Given the critical role of BSCs in maintaining epithelial integrity, understanding their alterations in COVID-19 is essential for developing effective therapeutic strategies. This study investigates the intrinsic properties of BSCs derived from COVID-19 patients and evaluates the modulatory effects of mesenchymal stem cells (MSCs). Through a combination of functional assessments and transcriptomic profiling, we identified key phenotypic and molecular deviations in COVID-19 patient-derived BSCs, including goblet cell hyperplasia, inflammation and fibrosis, which may underlie their contribution to PASC. Notably, MSC co-culture significantly mitigated these adverse effects, potentially through modulation of the interferon signalling pathway. This is the first study to isolate BSCs from COVID-19 patients in the Chinese population and establish a COVID-19 BSC-based xenograft model. Our findings reveal critical insights into the role of BSCs in epithelial repair and their inflammatory alterations in COVID-19 pathology, with potential relevance to PASC and virus-induced respiratory sequelae. Additionally, our study highlights MSC-based therapies as a promising strategy to address respiratory sequelae and persistent symptoms.}, } @article {pmid39863949, year = {2024}, author = {Somboonviboon, D and Aramareerak, P and Lertamornpong, A and Piyavechviratana, K and Pirompanich, P}, title = {Persistent COVID-19 symptoms and associated factors in a tertiary hospital in Thailand.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {12.1}, pages = {S318-S325}, doi = {10.3855/jidc.19332}, pmid = {39863949}, issn = {1972-2680}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/complications ; Middle Aged ; Thailand/epidemiology ; Cross-Sectional Studies ; *Tertiary Care Centers/statistics & numerical data ; Adult ; Aged ; *Dyspnea/epidemiology/etiology ; SARS-CoV-2 ; Risk Factors ; Prevalence ; Myalgia/epidemiology/etiology ; Sleep Initiation and Maintenance Disorders/epidemiology/etiology ; }, abstract = {INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with long-term symptoms, but the spectrum of these symptoms remains unclear. We aimed to identify the prevalence and factors associated with persistent symptoms in patients at the post-COVID-19 outpatient clinic.

METHODOLOGY: This cross-sectional, observational study included hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients followed-up at a post-COVID-19 clinic between September 2021 and January 2022. Persistent symptoms, defined as lasting > 4 weeks after infection, were analyzed alongside symptom timing (28-90, 91-120, and > 120 days) and associated factors using multivariate analysis.

RESULTS: Among 277 patients, mean (SD) age was 56 (16.6) years, and 58.5% were male. Of these, 80.9% reported at least one persistent symptom. Common symptoms included dyspnea (48.2%), insomnia (42.4%), and myalgia (42.1%). In multivariate analysis, being female [odds ratio (OR) 3.41; 95% confidence interval (CI) 1.5-7.76], and oxygen therapy (OR 3.39; 95% CI 1.3-8.81) were independently associated factors with persistent symptoms. High-sensitivity C-reactive protein (HsCRP) (> 75 mg/dL) was an independent risk factor for dyspnea (adjusted OR 2.29; 95% CI 1.28-4.12), and fatigue (adjusted OR 2.24; 95% CI 1.25-4). Oxygen therapy was an independent risk factor for neurologic symptoms, i.e. insomnia (adjusted OR 2.05; 95% CI 1.15-3.65), and brain fog (adjusted OR 2.02; 95% CI 1.14-3.58).

CONCLUSIONS: There was a high prevalence of persistent COVID-19 symptoms. The most common symptom was dyspnea. Female gender and oxygen supplementation were independent associated factors. Continuous follow-up of these patients is still required.}, } @article {pmid39863942, year = {2024}, author = {Korkmaz, MF and Şenkan, GE and Elmas Bozdemir, Ş and Korkmaz, M and Koç, İ and Oral, B}, title = {Evaluation of long-term pulmonary functions after COVID-19 infection in children: a longitudinal observational cohort study.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {12.1}, pages = {S267-S274}, doi = {10.3855/jidc.20123}, pmid = {39863942}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Child ; Male ; Female ; Adolescent ; Longitudinal Studies ; *Respiratory Function Tests ; Prospective Studies ; *Lung/physiopathology ; SARS-CoV-2 ; Severity of Illness Index ; Spirometry ; Cohort Studies ; }, abstract = {INTRODUCTION: We aimed to present the changes that may occur in pulmonary functions in children who experienced more severe coronavirus disease 2019 (COVID-19) during long-term follow-up.

METHODOLOGY: A prospective longitudinal observational cohort study was conducted with 34 pediatric patients (7-18 years) who were hospitalized with COVID-19 infection (moderate n = 25, severe n = 9), and followed up at our Pediatric Infection Outpatient Clinic for approximately two years. Pulmonary function tests (PFTs) were performed using spirometry.

RESULTS: Data from the hospitalization period revealed no significant differences between the severity groups in terms of demographic, clinical, laboratory, radiological, treatment, and outcome (p > 0.05). The median time interval between COVID-19 infection and PFTs was 15 months (range 11-29 months), and there was no significant difference between severity groups (p = 0.878). Eight patients (24%) had abnormal pulmonary functions; among them, seven had an obstructive pattern (21%) and one had a restrictive pattern (3%). The severity groups had no statistical difference in pulmonary functions (p = 0.105). While forced expiratory volume in 1 second (FEV1) %, FEV1/forced vital capacity (FVC)%, and forced expiratory flow during the middle half of FVC (FEF25-75%) ratios were lower in the severe patient group, Z-scores were similar. Among the patients continuing polyclinic follow-up, 41% had persistent respiratory symptoms before PFTs. No differences were observed in PFTs when compared based on the presence of symptoms (p > 0.05).

CONCLUSIONS: We observed no significant long-term differences in pulmonary function between moderate and severe COVID-19 cases in children.}, } @article {pmid39863405, year = {2025}, author = {Miller, A and Song, N and Sivan, M and Chowdhury, R and Burke, MR}, title = {Exploring the experiences of cognitive symptoms in Long COVID: a mixed-methods study in the UK.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e084999}, doi = {10.1136/bmjopen-2024-084999}, pmid = {39863405}, issn = {2044-6055}, mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *COVID-19/psychology/epidemiology ; United Kingdom/epidemiology ; Aged ; *Cognitive Dysfunction/psychology ; *SARS-CoV-2 ; Focus Groups ; Post-Acute COVID-19 Syndrome ; Young Adult ; Activities of Daily Living ; Qualitative Research ; Cognition ; }, abstract = {OBJECTIVE: To explore the lived experiences and extent of cognitive symptoms in Long COVID (LC) in a UK-based sample.

DESIGN: This study implemented a mixed-methods design. Eight focus groups were conducted to collect qualitative data, and the Framework Analysis was used to reveal the experiences and impact of cognitive symptoms. A self-report questionnaire was used to collect the quantitative data to assess the perceived change and extent of symptomology post COVID-19.

SETTING: Focus groups were conducted in April 2023 online via Zoom and in-person at the University of Leeds, UK.

PARTICIPANTS: 25 people with LC living in the UK participated in the study. Participants were aged 19-76 years (M=43.6 years, SD=14.7) and included 17 women and 8 men.

RESULTS: Reduced cognitive ability was among the most prevalent symptoms reported by the study participants. Three key themes were identified from the qualitative data: (1) rich accounts of cognitive symptoms; (2) the impact on physical function and psychological well-being and (3) symptom management. Descriptions of cognitive symptoms included impairments in memory, attention, language, executive function and processing speed. Cognitive symptoms had a profound impact on physical functioning and psychological well-being, including reduced ability to work and complete activities of daily living. Strategies used for symptom management varied in effectiveness.

CONCLUSION: Cognitive dysfunction in LC appears to be exacerbated by vicious cycle of withdrawal from daily life including loss of employment, physical inactivity and social isolation driving low mood, anxiety and poor cognitive functioning. Previous evidence has revealed the anatomical and physiological biomarkers in the brain affecting cognition in LC. To synthesise these contributing factors, we propose the Long-COVID Interacting Network of factors affecting Cognitive Symptoms. This framework is designed to inform clinicians and researchers to take a comprehensive approach towards LC rehabilitation, targeting the neural, individual and lifestyle factors.}, } @article {pmid39862702, year = {2025}, author = {Lim, HX and Khalid, K and Abdullah, ADI and Lee, LH and Raja Ali, RA}, title = {Subphenotypes of Long COVID and the clinical applications of probiotics.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {183}, number = {}, pages = {117855}, doi = {10.1016/j.biopha.2025.117855}, pmid = {39862702}, issn = {1950-6007}, abstract = {As the number of infections and deaths attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to rise, it is now becoming apparent that the health impacts of the Coronavirus disease (COVID-19) may not be limited to infection and the subsequent resolution of symptoms. Reports have shown that patients with SARS-CoV-2 infection may experience multiple symptoms across different organ systems that are associated with adverse health outcomes and develop new cardiac, renal, respiratory, musculoskeletal, and nervous conditions, a condition known as Long COVID or the post-acute sequelae of COVID-19 (PASC). This review provides insights into distinct subphenotypes of Long COVID and identifies microbiota dysbiosis as a common theme and crucial target for future therapies. Another important finding is that Long COVID is associated with prolonged and increased inflammation, potentially attributable to immune system dysfunction. A promising solution lies in the potential of probiotics to mitigate Long COVID symptoms by restoring gut microbiota balance and modulating the immune response. By evaluating the current clinical development landscape of the use of probiotics to treat Long COVID symptoms, this paper provides recommendations for future research by stressing the need to understand the modulation of bacterium strains followed by probiotic therapy to understand the association of microbiota dysbiosis with Long COVID symptoms. This will facilitate the development of effective probiotic formulations that could serve as reliable therapies against Long COVID.}, } @article {pmid39861887, year = {2025}, author = {Vanderheiden, A and Diamond, MS}, title = {Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.}, journal = {Viruses}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/v17010098}, pmid = {39861887}, issn = {1999-4915}, support = {F32 NS128065/NH/NIH HHS/United States ; P01 AI168347/NH/NIH HHS/United States ; R01 AI157155/NH/NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/complications/virology ; *Disease Models, Animal ; Mice ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Humans ; Cricetinae ; Primates ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice. We focus on neurological, gastrointestinal, and cardiovascular PASC and highlight advances in mechanistic insight that have been made using these animal models, as well as discussing the sequelae that warrant continued and intensive research.}, } @article {pmid39861434, year = {2025}, author = {Atieh, O and Daher, J and Durieux, JC and Abboud, M and Labbato, D and Baissary, J and Koberssy, Z and Ailstock, K and Cummings, M and Funderburg, NT and McComsey, GA}, title = {Vitamins K2 and D3 Improve Long COVID, Fungal Translocation, and Inflammation: Randomized Controlled Trial.}, journal = {Nutrients}, volume = {17}, number = {2}, pages = {}, doi = {10.3390/nu17020304}, pmid = {39861434}, issn = {2072-6643}, support = {UM1TR004528//Clinical and Translational Science Collaborative of Northern Ohio/ ; 0//the Kimble Foundation/ ; 0//CanPrev Natural Health Products/ ; }, mesh = {Humans ; Female ; Male ; *Vitamin K 2/therapeutic use ; Middle Aged ; *Cholecalciferol/therapeutic use ; *Inflammation/drug therapy ; *COVID-19 ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; Adult ; COVID-19 Drug Treatment ; Fungi ; Biomarkers/blood ; Vitamins/therapeutic use ; }, abstract = {BACKGROUND: Long COVID (LC) is characterized by persistent symptoms at least 3 months after a SARS-COV-2 infection. LC has been associated with fungal translocation, gut dysfunction, and enhanced systemic inflammation. Currently, there is no approved treatment for this condition. The anti-inflammatory effect of vitamins K2 and D3 was shown to help attenuate the course of acute COVID-19 infection.

OBJECTIVE AND HYPOTHESIS: This trial aims to investigate the effects of vitamins K2/D3 on LC symptoms, as well as gut and inflammatory markers, in people with established long COVID. Our hypothesis is that by attenuating systemic inflammation, vitamins K2/D3 will improve long COVID symptoms.

METHODS: This single-site randomized controlled study enrolled adults experiencing ≥2 moderate LC symptoms at least 3 months after a COVID-19 infection. The RECOVER Long COVID Research Index and number and type of LC symptoms were considered. Participants were randomized 2:1 to daily 240 µg K2 (pure MK-7 form) and 2000 UI vitamin D3 or standard of care (SOC) for 24 weeks. The endpoints were changes in symptomatology and in select inflammatory, metabolic, and gut biomarkers at 24 weeks.

RESULTS: We enrolled 151 participants (n = 98 received vit K2/D3 and 53 received SOC). The median age was 46 years; 71% were female and 29% were non-white. Baseline demographics were balanced between groups. At 24 weeks, the active treatment group only had a sharp increase in 25(OH) D, indicating good treatment adherence. In the vitamin K2/D3 arm, there was a 7.1% decrease in the proportion who had an LC Index ≥12 (vs. a 7.2% increase in the SOC group; p = 0.01). The average number of LC symptoms remained stable in the vitamin K2/D3 arm but increased in the SOC arm (p = 0.03). Additionally, reductions in oxidized LDL, inflammatory markers sTNF-RI and sCD163, and fungal translocation marker (1,3)-β-d-glucan were observed in the vitamin K2/D3 arm compared to the SOC arm (p < 0.01) over 24 weeks.

CONCLUSIONS: Vitamins K2/D3 improved the RECOVER Long COVID Index, the number of LC symptoms, and several gut and inflammatory markers. Vitamins K2/D3 provide a promising safe intervention for people suffering from long COVID.}, } @article {pmid39860512, year = {2025}, author = {Guntinas-Lichius, O and Bitter, T and Takes, R and Lee, VHF and Saba, NF and Mäkitie, AA and Kowalski, LP and Nixon, IJ and Ferlito, A}, title = {Post COVID-19 and Long COVID Symptoms in Otorhinolaryngology-A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/jcm14020506}, pmid = {39860512}, issn = {2077-0383}, abstract = {Post/Long COVID (syndrome) is defined as a condition with symptoms persisting for more than 12 weeks after the onset of SARS-CoV-2 infection that cannot be explained otherwise. The prevalence of self-reported otorhinolaryngological Post/Long COVID symptoms is high. The aim of this review was to analyze the current literature regarding the actual prevalence, knowledge of the etiopathology, and evidence-based treatment recommendations of otorhinolaryngology-related Post/Long COVID symptoms. A systematic literature search of articles published since 2019 in PubMed and ScienceDirect was performed and resulted in 108 articles. These were the basis for this review and formed a comprehensive series of consented therapy statements on the most important of otorhinolaryngology-related Post/Long COVID symptoms. Otorhinolaryngological symptoms did not appear isolated but as part of a multi-organ syndrome. Self-reported otorhinolaryngology-related Post/Long COVID symptoms were often not confirmed by objective testing. The confirmed prevalence estimated for anosmia, dysgeusia, cough, facial palsy, hoarseness/dysphonia, acute hearing loss, tinnitus, and vertigo/dizziness was about 4%, 2%, 4-19%, 0%, 17-20%, 8%, 20%, and 5-26%, respectively. There are manifold theoretical concepts of the etiopathology of different symptoms, but there is no clear evidence-based proof. This certainly contributes to the fact that there is no effective specific treatment option for any of the symptoms mentioned. Healthcare pathways must be established so that otorhinolaryngological Post/Long COVID symptoms can be recognized and evaluated and otorhinolaryngologists can provide counseling. This would also help to establish and selectively include patients in clinical trials investigating specific therapeutic concepts.}, } @article {pmid39860412, year = {2025}, author = {Petrou, D and Marinaki, S and Kriki, P and Flouda, S and Venetsanopoulou, A and Voulgari, P and Sardeli, A and Drouzas, K and Panagoutsos, S and Liapis, G and Gakiopoulou, H and Lionaki, S}, title = {Safety Profile of SARS-CoV-2 Vaccination in Patients with Lupus Nephritis: A Retrospective Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/jcm14020406}, pmid = {39860412}, issn = {2077-0383}, abstract = {Objectives: Vaccination against SARS-CoV-2 has been vital in alleviating the spread of the recent pandemic. We aimed to estimate the frequency and type of adverse events related to SARS-CoV-2 vaccine in patients with lupus nephritis (LN), and assess its impact, if any, on the risk of subsequent reactivation of nephritis. Methods: This was a retrospective, multicenter study which included patients with biopsy-proven LN, who had received at least one vaccine dose. Patients who ended up with end-stage kidney disease (ESKD) prior to vaccination or were diagnosed with LN after vaccination were excluded. Adverse events, systemic or local, COVID-19 outcomes (full recovery, death, or long COVID-19), outcome of LN (remission, refractory disease, relapse, ESKD or death), demographics, laboratory measurements, and immunosuppressive regimens were recorded. Results: Sixty-seven patients were included. The median age was 33 (20-46) years. Induction therapy for LN was administered to 92.5% of patients and 74.6% received maintenance therapy. Of these, 94.02% were in remission at vaccination. The BNT162b2 mRNA vaccine was administered in 97.01% of cases, with mild systemic adverse symptoms in 28.35% (myalgias 17.91%, headache 13.43%, arthralgias 13.43%, and fever 10.44%) and local adverse effects in 35.82% (pain 25.37%, swelling 13.43%). Overall, among patients in remission upon vaccination, two (3.17%) experienced a LN relapse within 5.75 (±0.25) months, while 75% of those with active disease at vaccination achieved remission within 21 (±2) months. Conclusions: SARS-CoV-2 vaccination appears safe for LN patients without serious adverse events occurring, and there is no significant impact in the clinical course of the disease.}, } @article {pmid39860384, year = {2025}, author = {Basaca, DG and Jugănaru, I and Belei, O and Nicoară, DM and Asproniu, R and Stoicescu, ER and Mărginean, O}, title = {Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health-A Comprehensive Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/jcm14020378}, pmid = {39860384}, issn = {2077-0383}, abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies.}, } @article {pmid39859379, year = {2025}, author = {Dos Santos Brito, WR and de Brito, WB and Dos Santos Ferreira, F and Santana, EGM and da Costa Lopes, J and da Silva Graça Amoras, E and Lima, SS and Dos Santos, EF and da Costa, FP and de Sarges, KML and Cantanhede, MHD and de Brito, MTFM and da Silva, ALS and de Meira Leite, M and de Nazaré do Socorro de Almeida Viana, M and Rodrigues, FBB and da Silva, R and Viana, GMR and do Socorro Souza Chaves, T and de Oliveira Lameira Veríssimo, A and da Silva Carvalho, M and Henriques, DF and da Silva, CP and Nunes, JAL and Costa, IB and Brasil-Costa, I and Quaresma, JAS and Cayres-Vallinoto, IMV and Reis, LO and Falcão, LFM and Dos Santos, EJM and Vallinoto, ACR and Queiroz, MAF}, title = {Polymorphisms Influence the Expression of the Fas and FasL Genes in COVID-19.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, doi = {10.3390/ijms26020666}, pmid = {39859379}, issn = {1422-0067}, support = {n° 304835/2022-6, n° 401235/2020-3; n° 302935/2021-5; n° 303837/2023-3, n° 310135/2022-2//National Council for Scientific and Technological Development/ ; n° 406360/2022-7//Institute National Institute of Science and Technology in Emerging and Reemerging Viruses (INCT-VER)/ ; n° 005/2020//Amazon Foundation for Studies and Research of Pará (FAPESPA)/ ; n° 09/2021//Secretariat of Science, Technology and Higher Professional and Technological Education (SECTET)/ ; 88887.506617/2020-00 and 88887.657670/2021-00//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; *COVID-19/genetics/blood/virology ; *Fas Ligand Protein/genetics ; *fas Receptor/genetics ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; Aged ; Polymorphism, Single Nucleotide ; Genotype ; Adult ; Interferon-gamma/genetics/blood ; Severity of Illness Index ; }, abstract = {The apoptotic molecule Fas and its ligand FasL are involved in the process of T-lymphocyte death, which may lead to lymphopenia, a characteristic of severe coronavirus disease 2019 (COVID-19). In this study, we investigated the influence of polymorphisms in the FAS and FASL genes, FAS and FASL gene expression, and plasma cytokine levels on COVID-19 severity and long COVID occurrence. A total of 116 individuals with severe COVID-19 and 254 with the non-severe form of the disease were evaluated. In the post-COVID-19 period, samples from 196 individuals with long COVID and 67 from people who did not have long COVID were included. Genotyping and quantification of gene expression were performed via real-time PCR, and cytokine measurement was performed via flow cytometry. The AA genotype for FAS rs1800682 (A/G) and the TT genotype for FASL rs763110 (C/T) were associated with increased FAS and FASL gene expression, respectively (p < 0.005). Higher plasma IFN-γ levels were associated with higher FAS and FASL gene expression (p < 0.05). Among individuals with non-severe COVID-19, carriers of the AA genotype for FAS rs1800682 (A/G) had higher levels of FAS expression, more symptoms, and higher IFN-γ levels (p < 0.05). No association of the evaluated markers with long COVID were observed. The AA genotype of FAS rs1800682 (A/G) and the TT genotype of FASL rs763110 (C/T) influence the levels of FAS and FASL gene expression. Higher gene expression of FAS and FASL may lead to greater inflammation in COVID-19 patients, with higher levels of IFN-γ and T lymphocyte death.}, } @article {pmid39859348, year = {2025}, author = {Tsilioni, I and Kempuraj, D and Theoharides, TC}, title = {Nobiletin and Eriodictyol Suppress Release of IL-1β, CXCL8, IL-6, and MMP-9 from LPS, SARS-CoV-2 Spike Protein, and Ochratoxin A-Stimulated Human Microglia.}, journal = {International journal of molecular sciences}, volume = {26}, number = {2}, pages = {}, doi = {10.3390/ijms26020636}, pmid = {39859348}, issn = {1422-0067}, support = {1-2021//CAS BioSciences (Costa Mesa, CA)/ ; }, mesh = {Humans ; *Microglia/drug effects/metabolism/virology ; *Ochratoxins/pharmacology ; *Lipopolysaccharides/pharmacology ; *Flavones/pharmacology ; *Matrix Metalloproteinase 9/metabolism ; *Interleukin-6/metabolism ; *Interleukin-1beta/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism ; *SARS-CoV-2/drug effects ; *Flavanones/pharmacology ; *Interleukin-8/metabolism ; Cell Line ; COVID-19 Drug Treatment ; Anti-Inflammatory Agents/pharmacology ; COVID-19/virology/metabolism ; }, abstract = {Neuroinflammation is involved in various neurological and neurodegenerative disorders in which the activation of microglia is one of the key factors. In this study, we examined the anti-inflammatory effects of the flavonoids nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) and eriodictyol (3',4',5,7-tetraxydroxyflavanone) on human microglia cell line activation stimulated by either lipopolysaccharide (LPS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length Spike protein (FL-Spike), or the mycotoxin ochratoxin A (OTA). Human microglia were preincubated with the flavonoids (10, 50, and 100 µM) for 2 h, following which, they were stimulated for 24 h. The inflammatory mediators interleukin-1 beta (IL-1β), chemokine (C-X-C motif) ligand 8 (CXCL8), IL-6, and matrix metalloproteinase-9 (MMP-9) were quantified in the cell culture supernatant by enzyme-linked immunosorbent assay (ELISA). Both nobiletin and eriodictyol significantly inhibited the LPS, FL-Spike, and OTA-stimulated release of IL-1β, CXCL8, IL-6, and MMP-9 at 50 and 100 µM, while, in most cases, nobiletin was also effective at 10 µM, with the most pronounced reductions at 100 µM. These findings suggest that both nobiletin and eriodictyol are potent inhibitors of the pathogen-stimulated microglial release of inflammatory mediators, highlighting their potential for therapeutic application in neuroinflammatory diseases, such as long COVID.}, } @article {pmid39859068, year = {2025}, author = {Ülker Ekşi, B and Kısa, EP and Ertan Harputlu, Ö and Kara Kaya, B and Hoşbay, Z and Akıncı, B}, title = {Exploring Medium- and Long-Term Respiratory and Functional Sequelae in Young Adults Post-COVID-19.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {1}, pages = {}, doi = {10.3390/medicina61010086}, pmid = {39859068}, issn = {1648-9144}, support = {2020-01-19//Research Fund of Biruni University Biratto Directorate/ ; }, mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; Adult ; Young Adult ; Muscle Strength/physiology ; Adolescent ; Dyspnea/physiopathology/etiology ; SARS-CoV-2 ; Fatigue/etiology/physiopathology ; Post-Acute COVID-19 Syndrome ; Walk Test/methods ; Hand Strength/physiology ; Respiratory Function Tests ; Case-Control Studies ; }, abstract = {Background and Objectives: Long COVID-19 syndrome may cause difficulties in functionality during daily life in young people. Our objective was to investigate the respiratory and functional sequelae in young adults with asymptomatic or mild COVID-19 compared with healthy peers 3-6 months and 6-12 months after COVID-19 infection. Materials and Methods: Participants aged 18-25 who had COVID-19 within the last 3-6 months (Post-COVID Group 1, n = 25) and 6-12 months (Post-COVID Group 2, n = 25) and age-gender-matched healthy controls (n = 25) were included in this study. Respiratory functions and muscle strength were measured. Physical function was assessed with 6 min walking test (6MWT) and an Incremental Shuttle Walk Test (ISWT). The 1 min sit-to-stand test (1-MSTST) and hand grip strength (HGS) were used to assess muscle performance. Fatigue and dyspnea severity were questioned. Results: The FVC%pred (p = 0.023) and MEP (p = 0.034) were higher, and 1-MSTST repetitions were lower in Post-COVID Group-1 compared to Post-COVID Group-2 (p = 0.029). The PEF%pred (p = 0.025), MEP (p = 0.001), and ISWT distance were lower in Post-COVID Group-2 compared to healthy controls. The number of 1-MSTST repetitions and 6MWT distance were lower in Post-COVID Group-1 (p = 0.003, p = 0.001) and Post-COVID Group-2 (p = 0.003, p = 0.017) than in healthy controls. Exercise-induced blood lactate change during the ISWT, HGS, fatigue, and dyspnea were not significantly different between post-COVID groups and healthy controls. Conclusions: Young adults who pass asymptomatic or mild SARS-CoV-2 infection exhibit a decline in FVC%pred, PEF%pred, lower extremity muscle performance, and physical function within 3-6 months. In addition, the deterioration in respiratory and physical functions becomes apparent within 6-12 months.}, } @article {pmid39857859, year = {2024}, author = {Floridia, M and Buonsenso, D and Macculi, L and Weimer, LE and Giuliano, M and Pricci, F and Bianchi, L and Toraldo, DM and Onder, G and The Iss Long-Covid Study Group, }, title = {Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/children12010028}, pmid = {39857859}, issn = {2227-9067}, support = {I85F21003410005//Italian Ministry of Health/ ; }, abstract = {BACKGROUND: Few studies have evaluated long-COVID in adolescents.

METHODS: Cohort study. Demographics, clinical data, and the presence of 30 symptoms were collected with a modified WHO form. Mean values were compared by Student's t test and proportions by the chi-square test or Fisher test, with trends over time analysed using the chi-square test for trend. Potential risk factors independently associated with persisting symptoms were evaluated in a multivariable logistic regression model. Clustering of cases was analysed by two-step automatic clustering.

RESULTS: A total of 97 adolescents aged 12-17 (54.6% females, 45.4% males) were evaluated. After a mean interval of 96 days (SD 52) from acute infection, the mean number of symptoms (2.8 overall) was higher for pre-Omicron (3.2 vs. 2.5 in Omicron, p = 0.046) and moderate/severe acute infections (4.2 vs. 2.7 in mild, p = 0.023). Fatigue (62.9%) and dyspnea (43.3%) were the most common symptoms, followed by headache (28.9%), thoracic pain (22.7%), diarrhea (20.6%), palpitations/tachycardia (17.5%), articular pain (15.5%), difficult concentration (14.4%), muscle pain (12.4%), taste reduction (8.2%), smell reduction (8.2%), fever (6.2%), and skin disorders (5.2%). The symptom profile was similar in males and females but showed significant differences from that observed in concurrently followed adults. After a mean interval of 340 days from infection, 45.3% still presented symptoms, with persistence associated with higher number of initial symptoms. Two clusters were defined that differed in the phase of acute infection and the number and profile of symptoms.

CONCLUSIONS: Long-COVID manifestations in adolescents may differ from those observed in adults. Polisymptomaticity may predict long-term persistence.}, } @article {pmid39857750, year = {2025}, author = {Blitshteyn, S}, title = {Neuroinflammation at the Dorsolateral Inferior Medulla: A Possible Central Nervous System Localization for POTS and Long COVID.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/biomedicines13010166}, pmid = {39857750}, issn = {2227-9059}, abstract = {Both postural orthostatic tachycardia syndrome (POTS) and Long COVID are currently viewed as heterogeneous disorders with complex, multi-factorial and multi-systemic pathophysiology. POTS, one of the most common autonomic disorders, is a frequent sequela of SARS-CoV-2 infection. Both POTS and autonomic dysfunction, in general, are major pathophysiologic mechanisms of Long COVID. There is emerging evidence that neuroinflammation of the brainstem may be one of the mechanisms of POTS and Long COVID. This commentary argues that neuroinflammation at the dorsolateral inferior medulla is a possible central nervous system localization for POTS and Long COVID based on the limited scientific literature available to date and the neurologic manifestations of both disorders. Further studies involving advanced neuroimaging techniques and animal models with immunohistochemical brainstem tissue assessments are needed to understand how and why possible neuroinflammation at the dorsolateral inferior medulla may occur in patients with Long COVID, POTS and other disorders involving autonomic dysfunction.}, } @article {pmid39857653, year = {2024}, author = {Latifi, A and Flegr, J}, title = {Persistent Health and Cognitive Impairments up to Four Years Post-COVID-19 in Young Students: The Impact of Virus Variants and Vaccination Timing.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/biomedicines13010069}, pmid = {39857653}, issn = {2227-9059}, support = {22-20785S//Czech Science Foundation/ ; }, abstract = {Background: The long-term consequences of COVID-19 infection are becoming increasingly evident in recent studies. This repeated cross-sectional study aimed to explore the long-term health and cognitive effects of COVID-19, focusing on how virus variants, vaccination, illness severity, and time since infection impact post-COVID-19 outcomes. Methods: We examined three cohorts of university students (N = 584) and used non-parametric methods to assess correlations of various health and cognitive variables with SARS-CoV-2 infection, COVID-19 severity, vaccination status, time since infection, time since vaccination, and virus variants. Results: Our results suggest that some health and cognitive impairments may persist, with some even appearing to progressively worsen-particularly fatigue in women and memory in men-up to four years post-infection. The data further indicate that the ancestral SARS-CoV-2 variant may have the most significant long-term impact, while the Omicron variant appears to have the least. Interestingly, the severity of the acute illness was not correlated with the variant of SARS-CoV-2. The analysis also revealed that individuals who contracted COVID-19 after vaccination had better health and cognitive outcomes compared to those infected before vaccination. Conclusions: Overall, our results indicate that even in young individuals who predominantly experienced only mild forms of the infection, a gradual decline in health and fitness can occur over a span of four years post-infection. Notably, some negative trends-at least in men-only began to stabilize or even reverse during the fourth year, whereas in women, these trends showed no such improvement. These findings suggest that the long-term public health impacts of COVID-19 may be more severe and affect a much broader population than is commonly assumed.}, } @article {pmid39857502, year = {2024}, author = {Amaral, CMSSBD and Valente, J and Goulart, CDL and Silva, BMD and Neto, AS and Cubas-Vega, N and Rezende, AG and Fernandes, E and Borba, MGS and Sampaio, V and Monteiro, W and Melo, GC and Lacerda, M and Arêas, GPT and Almeida-Val, F}, title = {Impact of Respiratory Support During Hospitalization on Functional Outcomes in Long COVID: A Post-Hoc Analysis of a Prospective Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {22}, number = {1}, pages = {}, doi = {10.3390/ijerph22010049}, pmid = {39857502}, issn = {1660-4601}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/therapy ; Prospective Studies ; *Hospitalization/statistics & numerical data ; Adult ; *Respiration, Artificial/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Muscle Strength ; }, abstract = {Post-acute COVID-19 syndrome (PACS) is characterized by the persistence of one or more symptoms after the acute phase, leading to physical disabilities. This study aims to investigate whether the functional capacity and respiratory function 120 days post-COVID-19 differed according to the level of respiratory support needed during hospitalization in acute COVID-19 in the pre-vaccine rollout period. We followed up with 118 COVID-19 hospitalized patients in the acute phase until 120 days post-acute disease, with patients split into a Non-Invasive Oxygen Therapy Group (OTG, n = 72), Invasive Mechanical Ventilation Group (IMV, n = 12), and Room Air Group (RAG, n = 34), assessing the body composition, respiratory muscle strength, pulmonary function, functional capacity, and muscle strength at the follow-up visit. In total, 54 individuals (45.8%) were female, with a median age of 48 years old (IQR: 41-58). We found that the group with IMV was older (p < 0.001), had more admissions to the ICU (p < 0.001), and had longer hospital stays (p < 0.001). There were no statistically significant differences between groups (OTG, IMV, and RAG) for the spirometry function (p = 0.31), DASI score (p = 0.77), manovacuometry (MIP p = 0.74; MEP p = 0.23), 6MWT (p = 0.43), and handgrip (p = 0.19) outcomes. At D120, the IMV group had an important loss of body muscle mass (BMM) and a higher BMM than RAG (p = 0.02). Reduction in MIP (p = 0.01) and MEP (p = 0.02) in the IMV group and OTG group when compared to the RAG was also observed. Functional outcomes at 120 days from COVID-19 hospitalization were not found to be associated with the levels of oxygen supplementation during acute disease in this group of participants.}, } @article {pmid39857222, year = {2025}, author = {Onik, G and Knapik, K and Górka, D and Sieroń, K}, title = {Health Resort Treatment Mitigates Neuropsychiatric Symptoms in Long COVID Patients: A Retrospective Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/healthcare13020196}, pmid = {39857222}, issn = {2227-9032}, abstract = {BACKGROUND/OBJECTIVES: Among the neuropsychiatric symptoms of long COVID, the following may be listed: sleep disturbances, headaches, anxiety, depression, dizziness, numbness, memory loss, and concentration difficulties. Various therapies have been implemented to mitigate these symptoms; however, health resort treatments that utilize a wide range of modalities stimulating multidirectional biological reactions may also be effective. The aim of this study was to assess the severity of neuropsychiatric symptoms in long COVID patients who qualified for health resort treatment, evaluate the effectiveness of health resort treatment in this group of patients, and evaluate the effect of balneological factors in the treatment course.

METHODS: A retrospective analysis of the medical records of 120 people with long COVID (69 women and 51 men) aged 42-79 who underwent health resort treatment in 2021 was performed. People were eligible for treatment at a lowland health resort based on a valid referral from a doctor. The treatment included balneological therapies, physical medicine modalities, exercise programs, health education, and psychological support. Patients assessed the severity of persistent neuropsychiatric symptoms on a 0-10 point scale before and after treatment.

RESULTS: After the treatment, the greatest improvement was noted in sleep disorders (2.47 ± 2.23 points vs. 0.86 ± 1.25 points, p < 0.00001) and dizziness (1.39 ± 1.94 points vs. 0.34 ± 0.76 points, p < 0.00001). The lowest improvement was observed in memory disorders (2.68 ± 2.5 points vs. 1 ± 1.4 points, p < 0.00001).

CONCLUSIONS: Patients with long COVID who qualified for health resort treatment reported mild neuropsychiatric symptoms. Health resort treatment mitigates neuropsychiatric symptoms, as it is a complex approach. Treatment that includes balneological factors improves symptoms to a greater extent. This method of treatment should be integrated into the standard treatment for long COVID.}, } @article {pmid39857123, year = {2025}, author = {Ferrara, E and Scaramuzzino, M and Murmura, G and D'Addazio, G and Sinjari, B}, title = {Emerging Evidence on Balneotherapy and Thermal Interventions in Post-COVID-19 Syndrome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/healthcare13020096}, pmid = {39857123}, issn = {2227-9032}, abstract = {BACKGROUND: Post-COVID-19 syndrome affects 10-60% of SARS-CoV-2 survivors. While conventional treatments show limited efficacy, emerging evidence suggests the potential benefits of balneotherapy in managing persistent symptoms. We aimed to systematically evaluate the efficacy and safety of balneotherapy and thermal treatment interventions in treating post-COVID-19 syndrome.

METHODS: We conducted a systematic review following PRISMA guidelines, searching major databases through 31 January 2024. Eligible studies included randomized controlled trials, observational studies, and pilot studies investigating thermal spa treatments for adult post-COVID-19 patients.

RESULTS: Analysis of six eligible studies (n = 617) demonstrated significant therapeutic benefits. The largest cohort (n = 159) showed 47% reduction in fatigue and 48% reduction in muscle pain (p < 0.01). Comprehensive spa therapy achieved complete symptom resolution in one-third of the participants. Combined spa-ubiquinol therapy improved metabolic function (p < 0.05). All interventions demonstrated favorable safety profiles.

CONCLUSIONS: Preliminary evidence suggests balneotherapy effectively ameliorates multiple post-COVID-19 symptoms, particularly fatigue, muscle pain, and exercise intolerance. While safety profiles appear favorable, larger randomized controlled trials with standardized protocols are needed to establish definitive therapeutic recommendations.}, } @article {pmid39857114, year = {2025}, author = {Eldien, HMS and Almaeen, AH and El Fath, AA and Taha, AE and Ahmed, R and Elfadil, H and Hetta, HF}, title = {Unlocking the Potential of RNA Sequencing in COVID-19: Toward Accurate Diagnosis and Personalized Medicine.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/diagnostics15020229}, pmid = {39857114}, issn = {2075-4418}, support = {(DSR 2020-04-2621)//Deanship of Scientific Research at Jouf University through research/ ; }, abstract = {COVID-19 has caused widespread morbidity and mortality, with its effects extending to multiple organ systems. Despite known risk factors for severe disease, including advanced age and underlying comorbidities, patient outcomes can vary significantly. This variability complicates efforts to predict disease progression and tailor treatment strategies. While diagnostic and therapeutic approaches are still under debate, RNA sequencing (RNAseq) has emerged as a promising tool to provide deeper insights into the pathophysiology of COVID-19 and guide personalized treatment. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. We employed Medical Subject Headings (MeSH) terms and relevant keywords to identify studies that explored the role of RNAseq in COVID-19 diagnostics, prognostics, and therapeutics. RNAseq has proven instrumental in identifying molecular biomarkers associated with disease severity in patients with COVID-19. It allows for the differentiation between asymptomatic and symptomatic individuals and sheds light on the immune response mechanisms that contribute to disease progression. In critically ill patients, RNAseq has been crucial for identifying key genes that may predict patient outcomes, guiding therapeutic decisions, and assessing the long-term effects of the virus. Additionally, RNAseq has helped in understanding the persistence of viral RNA after recovery, offering new insights into the management of post-acute sequelae, including long COVID. RNA sequencing significantly improves COVID-19 management, particularly for critically ill patients, by enhancing diagnostic accuracy, personalizing treatment, and predicting therapeutic responses. It refines patient stratification, improving outcomes, and holds promise for targeted interventions in both acute and long COVID.}, } @article {pmid39854988, year = {2025}, author = {Moreno-Gabriel, E and Bielsa-Pascual, J and Verdaguer, M and Carmona-Cervelló, M and Lamonja Vicente, N and León Gómez, BB and Violan, C and Torán-Monserrat, P}, title = {[Patients' experiences of long-covid neuropsychological symptoms in Catalonia: A phenomenological study].}, journal = {Atencion primaria}, volume = {57}, number = {6}, pages = {103214}, doi = {10.1016/j.aprim.2024.103214}, pmid = {39854988}, issn = {1578-1275}, abstract = {The objective was to describe the experiences of people living with neuropsychological symptomatology associated with long-covid, as well as identifying the barriers they encounter in their daily lives and the strategies they develop to deal with them. This is a descriptive qualitative study following an interpretative phenomenological perspective wich was held in Primary Care cin the Northern Metropolitan Area of Barcelona and the Germans Trias i Pujol University Hospital (Badalona, Spain). A total of 34 adults with any persistent neuropsychological symptoms of covid-19 (>12 weeks since disease onset) participated. In-depth individual interviews were conducted following a script of open-ended questions to elicit their narratives around the research objective. A total of 3 clusters detailing the life impact of long-covid and its neuropsychological symptomatology were identified: long-covid as life-breaking and life-changing; coping strategies; and (ac)knowledge (of) the emerging subjectivity. From the participants' accounts and the existing literature emerges the relevance of critically integrating lessons learned from analogous syndromes such as fibromyalgia and chronic fatigue, as well as involving patients in the design and implementation (even at the consultation level) of clinical practices that raise awareness of these neuropsychological sequelae (psychoeducation) both to other patients and to caregivers and professionals. This would facilitate a greater and better specialised psychological approach and reduce the stigma that still accompanies the condition. .}, } @article {pmid39854889, year = {2025}, author = {Plastina, AF}, title = {Long COVID patients' reconstruction of medical gaslighting discourse in online epistemic communities.}, journal = {Patient education and counseling}, volume = {134}, number = {}, pages = {108665}, doi = {10.1016/j.pec.2025.108665}, pmid = {39854889}, issn = {1873-5134}, abstract = {OBJECTIVE: To analyse long COVID patients' reconstruction of medical gaslighting (MG) discourse in online epistemic communities in order to identify the MG types experienced and unfold root causes.

METHOD: The mixed-methods of corpus‑based critical discourse analysis was applied to an ad hoc corpus of 18 threads (n = 1176 posts) from two sub-communities on the social media site Reddit. Comparative concordance analyses were performed on the two sub-corpora to semantically code concordance lines as MG types. Critical discourse analysis was conducted to uncover power/ideological drivers of MG discourse.

RESULTS: Keyness log‑likelihood statistical measures displayed higher values for the pronouns I, me, you, it, they and the noun doctor(s). KWIC (Key Word in Context) output for these items exhibited seven main MG types: scapegoating, downplay, treatment refusal, psychosomatic disorder, disbelief, denial and dismissal. Concordance lines revealed three major sites of contention - epistemic knowledge, epistemic authority, long COVID indeterminacy - where MG tactics operate through epistemic injustice, ignorance, discrimination and lack of epistemic humility.

CONCLUSION: MG discourse is triggered by deep-seated ideologies rather than by mere doctor-patient interaction as a face-saving strategy which faults patients as epistemic agents.

PRACTICAL IMPLICATIONS: Patients' social media mobilisation helps unmask MG tactics, raising providers' awareness of the need for perspective-taking to build collaborative doctor-patient relationships.}, } @article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, doi = {10.1080/19490976.2025.2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *COVID-19/therapy/microbiology ; *Probiotics/therapeutic use ; *Dysbiosis/therapy/microbiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Prebiotics/administration & dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, } @article {pmid39853911, year = {2025}, author = {Hou, Z and Ming, Y and Liu, J and Wang, Z}, title = {Potential Biomarkers for Predicting the Risk of Developing Into Long COVID After COVID-19 Infection.}, journal = {Immunity, inflammation and disease}, volume = {13}, number = {1}, pages = {e70137}, doi = {10.1002/iid3.70137}, pmid = {39853911}, issn = {2050-4527}, support = {//This study was supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2023C063YLL) and National Major Scientific and Technological Special Project for "Significant New Drug Development" (2017ZX09301059)./ ; }, mesh = {Humans ; *COVID-19/genetics/immunology ; *SARS-CoV-2/physiology/immunology ; *Biomarkers ; Post-Acute COVID-19 Syndrome ; Transcriptome ; Gene Expression Profiling ; Gene Ontology ; }, abstract = {BACKGROUND: Long COVID, a heterogeneous condition characterized by a range of physical and neuropsychiatric presentations, can be presented with a proportion of COVID-19-infected individuals.

METHODS: Transcriptomic data sets of those within gene expression profiles of COVID-19, long COVID, and healthy controls were retrieved from the GEO database. Differentially expressed genes (DEGs) falling under COVID-19 and long COVID were identified with R packages, and contemporaneously conducted module detection was performed with the Modular Pharmacology Platform (http://112.86.129.72:48081/). The integration of both DEGs and differentially expressed module-genes (DEMGs) regarding long COVID and COVID-19 was intersected by following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA).

RESULTS: There were 11 and 62 differentially expressed modules, 1837 and 179 DEGs, as well as 103 and 508 DEMGs acquiring identified for both COVID-19 and long COVID, notably enriched in the immune-correlated signaling pathways. The immune infiltrating cells of long COVID and COVID-19 were comparatively and respectively assessed via CIBERSORT, ssGSEA, and xCell algorithms. Subsequently, the screening of hub genes involved employing the SVM-RFE, RF, XGBoost algorithms, and logistic regression analysis. Among the 67 candidate genes were processed with machine learning algorithms and logistic regression, a subgroup consisting of CEP55, CDCA2, MELK, and DEPDC1B, was at last identified as potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infections. The predicting performance of the potential biomarkers was quantified with a ROC value of 0.8762542, which proved the combination of potential biomarkers provided the highest performance.

CONCLUSIONS: In summary, we identified a subgroup of potential biomarkers for predicting the risk of the progression into long COVID after COVID-19 infection, which could be partly elucidation of the associated molecular mechanisms for long COVID.}, } @article {pmid39853360, year = {2025}, author = {Jebrini, T and Stubbe, HC and Ruzicka, M and Adorjan, K}, title = {Neurocognitive challenges Post-COVID: current perspectives and future solutions.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {39853360}, issn = {1433-8491}, } @article {pmid39852767, year = {2024}, author = {Blitshteyn, S and Ruhoy, IS and Natbony, LR and Saperstein, DS}, title = {Internal Tremor in Long COVID May Be a Symptom of Dysautonomia and Small Fiber Neuropathy.}, journal = {Neurology international}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/neurolint17010002}, pmid = {39852767}, issn = {2035-8385}, abstract = {Background/Objectives: Internal tremor (IT) is often reported by patients with post-acute sequelae of SARS-CoV-2, also known as Long COVID, as a distressing and disabling symptom. Similarly, physicians are typically perplexed by the nature and etiology of IT and find it extremely challenging to manage. Methods: We describe a patient with Long COVID who experienced IT as part of post-COVID postural orthostatic tachycardia syndrome (POTS) and small fiber neuropathy (SFN) and review the limited literature available on this topic. Results: Our patient's IT improved significantly after intravenous saline infusions, but there was no effect on IT with oral hydration, increased oral sodium chloride intake, neuropathic pain medications, muscle relaxants, or medications used for the treatment of POTS. Conclusions: Based on this case, our clinical experience, and the limited literature available to date, we believe IT is a manifestation of POTS and SFN, which may be driven by hypovolemia, cerebral hypoperfusion, sympathetic overactivity, neuropathic pain, and mast cell hyperactivation. Subjective description, objective findings, and diagnostic and therapeutic considerations in patients with IT and Long COVID are discussed.}, } @article {pmid39850323, year = {2024}, author = {Stefanou, MI and Panagiotopoulos, E and Palaiodimou, L and Bakola, E and Smyrnis, N and Papadopoulou, M and Moschovos, C and Paraskevas, GP and Rizos, E and Boutati, E and Tzavellas, E and Gatzonis, S and Mengel, A and Giannopoulos, S and Tsiodras, S and Kimiskidis, VK and Tsivgoulis, G}, title = {Current update on the neurological manifestations of long COVID: more questions than answers.}, journal = {EXCLI journal}, volume = {23}, number = {}, pages = {1463-1486}, pmid = {39850323}, issn = {1611-2156}, abstract = {Since the outbreak of the COVID-19 pandemic, there has been a global surge in patients presenting with prolonged or late-onset debilitating sequelae of SARS-CoV-2 infection, colloquially termed long COVID. This narrative review provides an updated synthesis of the latest evidence on the neurological manifestations of long COVID, discussing its clinical phenotypes, underlying pathophysiology, while also presenting the current state of diagnostic and therapeutic approaches. Approximately one-third of COVID-19 survivors experience prolonged neurological sequelae that persist for at least 12-months post-infection, adversely affecting patients' quality of life. Core neurological manifestations comprise fatigue, post-exertional malaise, cognitive impairment, headache, lightheadedness ('brain fog'), sleep disturbances, taste or smell disorders, dysautonomia, anxiety, and depression. Some of these features overlap substantially with those reported in post-intensive-care syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, and postural-orthostatic-tachycardia syndrome. Advances in data-driven research utilizing electronic-health-records combined with machine learning and artificial intelligence have propelled the identification of long COVID sub-phenotypes. Furthermore, the evolving definitions reflect the dynamic conceptualization of long COVID in both research and clinical contexts. Although the underlying pathophysiology remains incompletely elucidated, neuroinflammatory responses, endotheliopathy, and metabolic imbalances, rather than direct viral neuroinvasion, are implicated in neurological sequelae. Genetic susceptibility has also emerged as a potential risk factor. While major limitations remain with existing definitions, collaborative strategies to standardize diagnostic approaches are needed. Current therapeutic paradigms advocate for multimodal approaches, integrating pharmacological and non-pharmacological interventions along with comprehensive rehabilitation programs. Although preliminary evidence of therapeutic efficacy has been provided by a number of clinical trials, methodological constraints limit the generalizability of this evidence. Preventive measures, notably vaccination, have proven integral for reducing the global burden of long COVID. Considering the healthcare and socioeconomic repercussions incurred by long COVID worldwide, international collaborative initiatives are warranted to address the remaining challenges in diagnosing and managing patients presenting with neurological sequelae. See also the graphical abstract(Fig. 1).}, } @article {pmid39850015, year = {2025}, author = {Rao, S and Azuero-Dajud, R and Lorman, V and Landeo-Gutierrez, J and Rhee, KE and Ryu, J and Kim, C and Carmilani, M and Gross, RS and Mohandas, S and Suresh, S and Bailey, LC and Castro, V and Senathirajah, Y and Esquenazi-Karonika, S and Murphy, S and Caddle, S and Kleinman, LC and Castro-Baucom, L and Oliveira, CR and Klein, JD and Chung, A and Cowell, LG and Madlock-Brown, C and Geary, CR and Sills, MR and Thorpe, LE and Szmuszkovicz, J and Tantisira, KG and , and , }, title = {Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.}, journal = {EClinicalMedicine}, volume = {80}, number = {}, pages = {103042}, pmid = {39850015}, issn = {2589-5370}, abstract = {BACKGROUND: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

METHODS: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.S, using electronic health record (EHR) data. Our cohort included those with a positive SARS-CoV-2 molecular, serology or antigen test, or with a COVID-19, multisystem inflammatory disease in children, or PASC diagnosis from February 29, 2020 to August 1, 2022. We identified children/youth with at least 2 codes associated with respiratory and neurologic PASC. We measured associations between sociodemographic and clinical characteristics and respiratory and neurologic PASC using odds ratios and 95% confidence intervals estimated from multivariable logistic regression models adjusted for other sociodemographic characteristics, social vulnerability index or area deprivation index, time period of cohort entry, presence and complexity of chronic respiratory (respectively, neurologic) condition and healthcare utilization.

FINDINGS: Among 771,725 children in the cohort, 203,365 (26.3%) had SARS-CoV-2 infection. Among children with documented infection, 3217 children had respiratory PASC and 2009 children/youth had neurologic PASC. In logistic regression models, children <5 years (Odds Ratio [OR] 1.78, 95% CI 1.62-1.97), and of Hispanic White descent (OR 1.19, 95% CI 1.05-1.35) had higher odds of having respiratory PASC. Children/youth living in regions with higher area deprivation indices (OR 1.25, 95% CI 1.10-1.420 for 60-79th percentile) and with chronic complex respiratory conditions (OR 3.28, 95% CI 2.91-3.70) also had higher odds of respiratory PASC. In contrast, older (OR 1.57, 95% CI 1.40-1.77 for those aged 12-17 years), non-Hispanic White individuals and those with chronic pre-existing neurologic conditions (OR 2.04, 95% CI 1.78-2.35) were more likely to have a neurologic PASC diagnosis.

INTERPRETATION: Racial and ethnic differences in healthcare utilization for neurologic and respiratory PASC may reflect social drivers of health and inequities in access to care.

FUNDING: National Institutes of Health.}, } @article {pmid39849406, year = {2025}, author = {Iqbal, NT and Khan, H and Khalid, A and Mahmood, SF and Nasir, N and Khanum, I and de Siqueira, I and Van Voorhis, W}, title = {Chronic inflammation in post-acute sequelae of COVID-19 modulates gut microbiome: a review of literature on COVID-19 sequelae and gut dysbiosis.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {22}, pmid = {39849406}, issn = {1528-3658}, support = {3U01AI151698//Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *Dysbiosis ; *Gastrointestinal Microbiome ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/physiology ; *Brain-Gut Axis ; Inflammation ; }, abstract = {BACKGROUND: Long COVID or Post-acute sequelae of COVID-19 is an emerging syndrome, recognized in COVID-19 patients who suffer from mild to severe illness and do not recover completely. Most studies define Long COVID, through symptoms like fatigue, brain fog, joint pain, and headache prevailing four or more weeks post-initial infection. Global variations in Long COVID presentation and symptoms make it challenging to standardize features of Long COVID. Long COVID appears to be accompanied by an auto-immune multi-faceted syndrome where the virus or viral antigen persistence causes continuous stimulation of the immune response, resulting in multi-organ immune dysregulation.

MAIN TEXT: This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis. Two proposed mechanisms are discussed here. The first mechanism is related to the dysfunction of angiotensin-converting enzyme 2 receptor due to Severe Acute Respiratory Syndrome Corona Virus 2 infection, leading to impaired mTOR pathway activation, reduced AMP secretion, and causing dysbiotic changes in the gut. Secondly, gut-brain axis dysregulation accompanied by decreased production of short-chain fatty acids, impaired enteroendocrine cell function, and increased leakiness of the gut, which favors translocation of pathogens or lipopolysaccharide in circulation causing the release of pro-inflammatory cytokines. The altered Hypothalamic-Pituitary-Adrenal axis is accompanied by the reduced level of neurotransmitter, and decreased stimulation of the vagus nerve, which may cause neuroinflammation and dysregulation of serum cortisol levels. The dysbiotic microbiome in Long COVID patients is characterized by a decrease in beneficial short chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcus, Dorea, and Bifidobacterium) and an increase in opportunistic bacteria (Corynebacterium, Streptococcus, Enterococcus). This dysbiosis is transient and may be impacted by interventions including probiotics, and dietary supplements.

CONCLUSIONS: Further studies are required to understand the geographic variation, racial and ethnic differences in phenotypes of Long COVID, the influence of viral strains on existing and emerging phenotypes, to explore long-term effects of gut dysbiosis, and gut-brain axis dysregulation, as well as the potential role of diet and probiotics in alleviating those symptoms.}, } @article {pmid39849379, year = {2025}, author = {Saigal, A and Xiao, S and Siddique, O and Naran, P and Bintalib, HM and Niklewicz, CN and Seligmann, G and Naidu, SB and Shah, AJ and Ogbonnaya, C and Hurst, JR and Lipman, MC and Mandal, S}, title = {Predictors of specialist care referrals (SCR) following emergency department review or hospital admission in adults with previous acute COVID-19: a prospective UK cohort study.}, journal = {BMC emergency medicine}, volume = {25}, number = {1}, pages = {11}, pmid = {39849379}, issn = {1471-227X}, mesh = {Humans ; *Referral and Consultation/statistics & numerical data ; *COVID-19/epidemiology/therapy ; Female ; *Emergency Service, Hospital/statistics & numerical data ; Male ; Prospective Studies ; Middle Aged ; Adult ; Hospitalization/statistics & numerical data ; United Kingdom/epidemiology ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Specialization ; London/epidemiology ; }, abstract = {BACKGROUND: Long-COVID research to date focuses on outcomes in non-hospitalised vs. hospitalised survivors. However Emergency Department attendees (post-ED) presenting with acute COVID-19 may experience less supported recovery compared to people admitted and discharged from hospital (post-hospitalised group, PH).

OBJECTIVE: We evaluated outcomes and predictors of specialty care referrals (SCR) in those with ongoing symptomatic Long-COVID, comparing post-ED and PH adults.

METHODS: This prospective observational cohort study evaluates 800 PH and 484 post-ED adults from a single hospital in London, United Kingdom. Participants had either confirmed laboratory-positive SARS-CoV-2 infection or clinically suspected acute COVID-19 and were offered post-COVID clinical follow-up at approximately six weeks after their ED attendance or inpatient discharge, to assess ongoing symptoms and support recovery. Multiple logistic regression determined associations with specialist care referrals (SCR) to respiratory, cardiology, physiotherapy (including chest physiotherapy), and mental health services.

RESULTS: Presence of at least one Long-COVID symptom was lower in adults attending ED services with acute COVID-19 compared to those hospitalised (70.1% post-ED vs. 79.5% PH adults, p < 0.001). Total number of Long-COVID symptoms was associated with increased SCR in all patients (adjusted odds ratio (aOR) = 1.26, 95%CI:1.16, 1.36, p < 0.001), with post-ED adults more likely to need a SCR overall (aOR = 1.82, 95%CI:1.19, 2.79, p = 0.006). Post-ED adults had higher SCR to both physiotherapy (aOR = 2.59, 95%CI:1.35, 4.96, p = 0.004) and mental health services (aOR = 3.84, 95%CI:2.00, 7.37, p < 0.001), with pre-existing mental illness linked to the latter (aOR = 4.08, 95%CI:1.07, 15.6, p = 0.04).

CONCLUSIONS: We demonstrate greater specialist care referrals to mental health and physiotherapy services in patients attending the ED and discharged with acute COVID-19, compared to those admitted, despite lower ongoing COVID-19 symptom burden. Total number of symptoms, pre-existing co-morbidity such as smoking status, cardiac co-morbidities, and mental health illnesses may predict those requiring healthcare input. This information may enable better post-COVID support for ED attendees, a distinct group who should not be neglected when preparing for future pandemics.

TRIAL REGISTRATION: This study had HRA approval (20/HRA/4928).}, } @article {pmid39102190, year = {2024}, author = {Widmann, CN and Henkel, C and Seibert, S}, title = {"Brain Fog" After COVID-19 Infection: How the Field of Neuropsychology Can Help Clear the Air.}, journal = {Advances in experimental medicine and biology}, volume = {1458}, number = {}, pages = {59-76}, pmid = {39102190}, issn = {0065-2598}, mesh = {Humans ; Attention/physiology ; Brain/physiopathology/virology ; Cognition/physiology ; *Cognitive Dysfunction/physiopathology/psychology/rehabilitation/virology ; Executive Function/physiology ; *Mental Fatigue/physiopathology/psychology/rehabilitation/virology ; *Neuropsychology/methods ; Pandemics ; *Post-Acute COVID-19 Syndrome/physiopathology/psychology/rehabilitation/virology ; SARS-CoV-2/pathogenicity ; Telemedicine ; }, abstract = {The chapter explores the role of neuropsychology in understanding brain fog as a subjective complaint in the context of COVID-19. It discusses the historical and medical significance of the term "brain fog" and its psychological and neurological aspects. The chapter identifies the cognitive domains commonly affected by brain fog, such as attention, executive function, memory, and language. Additionally, it emphasizes the impact of societal changes during the COVID-19 pandemic on the general population as a crucial backdrop for understanding the issue. The chapter also highlights the important role of clinical and research neuropsychologists in gaining clarity on grouped data and individual patients' cognitive and emotional difficulties after COVID-19 infection. It discusses indications for neuropsychological rehabilitation and therapy and describes typical therapy phases and methods, including new approaches like telemedicine, virtual reality, and mobile app-based rehabilitation and self-tracking. The chapter underscores that experiences of brain fog can vary among COVID-19 patients and may change over time. It provides clinicians and interested parties with an in-depth understanding of brain fog and its manifestations, concomitant subtypes, and concrete strategies for addressing it. The chapter emphasizes the critical role of neuropsychology in scientifically examining brain fog and advocating for personalized approaches to cognitive rehabilitation.}, } @article {pmid39849116, year = {2025}, author = {Kovács, F and Posvai, T and Zsáry, E and Kolonics, F and Garai, R and Herczeg, V and Czárán, D and Takács, J and Szabó, AJ and Krivácsy, P and Csépányi-Kömi, R}, title = {Correction: Long COVID syndrome in children: neutrophilic granulocyte dysfunction and its correlation with disease severity.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41390-025-03888-3}, pmid = {39849116}, issn = {1530-0447}, } @article {pmid39849114, year = {2025}, author = {Buonsenso, D and Cotugno, N and Amodio, D and Pascucci, GR and Di Sante, G and Pighi, C and Morrocchi, E and Pucci, A and Olivieri, G and Colantoni, N and Romani, L and Rotili, A and Neri, A and Morello, R and Sali, M and Tremoulet, A and Raffaelli, F and Zampino, G and Rossi, P and Valentini, P and Palma, P}, title = {Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {39849114}, issn = {1530-0447}, abstract = {BACKGROUND: Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.

METHODS: We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age. Children were classified as Long COVID if symptoms persisted for at least 8 weeks since the initial infection, negatively impacted daily life and could not be explained otherwise.

RESULTS: 112 children were included in the study, including 34 children fulfilling clinical criteria of Long COVID, 32 acute SARS-CoV-2 infection, 27 MIS-C and 19 healthy controls. Compared with controls, pediatric Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. A Machine Learning model based on proteomic profile was able to identify LC with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97.

CONCLUSIONS: Pediatric Long COVID patients have a well distinct blood protein signature marked by increased ongoing general and endothelial inflammation, similarly as happens in adults.

IMPACT: Pediatric Long COVID has a distinct blood protein signature marked by increased ongoing general and endothelial inflammation. This is the first study studying and documenting proinflammatory profile in blood samples of children with long COVID. Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a. A proteomic profile was able to identify Long COVID with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97. These findings may inform development of future diagnostic tests.}, } @article {pmid39848792, year = {2025}, author = {Selvan, H and Rana, M}, title = {Recurrent nodular episcleritis as a manifestation of long COVID.}, journal = {BMJ case reports}, volume = {18}, number = {1}, pages = {}, doi = {10.1136/bcr-2024-262244}, pmid = {39848792}, issn = {1757-790X}, mesh = {Humans ; Female ; *Scleritis/virology/etiology/diagnosis/drug therapy ; *COVID-19/complications/diagnosis ; Middle Aged ; *Recurrence ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {A woman in her 50s presented with redness, eye pain, watering and photophobia of the left eye starting 1 week after she tested positive for COVID-19. She was diagnosed with left eye episcleritis and started on topical steroids. As the steroids were being gradually tapered, she developed a recurrence. The cycle of treatment-tapering-recurrence repeated itself such that nine episodes were noted within a span of 3 years. An exhaustive diagnostic work-up including infective and autoimmune blood tests, rheumatology assessment and COVID-19 conjunctival swabs and tear samples were done, and no underlying conditions or triggers could be identified, attributing 'long COVID' as the likely causative. Long COVID is the continuation or development of new symptoms after the initial COVID-19 infection, with no other explanation. It is estimated to affect nearly 65 million people worldwide, with >200 symptoms, involving different organ systems. The ocular manifestations of long COVID are less well-known.}, } @article {pmid39848702, year = {2025}, author = {León-Gómez, BB and Carmona-Cervelló, M and Dacosta-Aguayo, R and Lamonja-Vicente, N and Bielsa-Pascual, J and López-Lifante, VM and Zamora-Putin, V and Molist, G and Montero-Alia, P and Pachón-Camacho, A and Moreno-Gabriel, E and García-Sierra, R and Bermudo-Gallaguet, A and Chacón, C and Costa-Garrido, A and Muñoz-Moreno, JA and Mateu, L and Mataró, M and Prado, JG and Martínez-Cáceres, E and Massanella, M and Violán, C and Torán-Monserrat, P}, title = {Prevalence and severity of anxiety, stress, and depression in long COVID among adults in Barcelona.}, journal = {BJGP open}, volume = {}, number = {}, pages = {}, doi = {10.3399/BJGPO.2024.0098}, pmid = {39848702}, issn = {2398-3795}, abstract = {BACKGROUND: The COVID-19 pandemic's long-term mental health implications are increasingly concerning, especially among patients suffering post-acute sequelae of SARS-CoV-2 infection: Long COVID (LC) patients.

AIM: This study explores the presence and distribution of anxiety, depression, and stress in LC individuals with cognitive complaints in northern Barcelona (Spain).

DESIGN & SETTINGS: This cross-sectional study involved 155 diagnosed LC individuals from the "Aliança ProHEpiC-19 Cognitiu (APC)" project.

METHOD: Demographic data and health behavior variables were collected, and the Depression, Anxiety, and Stress Scale (DASS-21) was self-administered to assess mental health. Descriptive statistics, chi-squared tests, and Poisson regression models were used for data analysis.

RESULTS: 'Severe' stress and 'Extremely Severe' anxiety were prevalent in the sample. There were significant differences in anxiety and depression based on age and job role, with older individuals and non-healthcare workers showing higher relative risks.

CONCLUSIONS: Our study highlights the significant mental health burden in LC patients, underscoring the need for targeted interventions, especially among adults over 45 years old and non-healthcare workers. Further research is needed to better understand LC's complex mental health impacts and develop effective clinical management strategies.}, } @article {pmid39847900, year = {2025}, author = {Moullec, Y and Saint-Aubert, J and Lécuyer, A and Bidard, Q and Bonan, I and Cogné, M}, title = {Simulated breathing in virtual reality does not affect perceived effort during the physical rehabilitation of people with long COVID.}, journal = {Annals of physical and rehabilitation medicine}, volume = {68}, number = {4}, pages = {101922}, doi = {10.1016/j.rehab.2024.101922}, pmid = {39847900}, issn = {1877-0665}, abstract = {OBJECTIVE: To assess the effectiveness of simulated breathing in virtual reality (VR) for manipulating the level of perceived effort of people with long COVID during sessions of physical rehabilitation.

METHODS: We conducted a within-participants randomized prospective study during a cycling exercise in immersive VR with three counterbalanced conditions of simulated breathing: slower breathing, neutral breathing, and faster breathing compared to theirs. 37 participants with long COVID and deconditioning were included in the study, 36 of which could finish the experiment.

RESULTS: The study did not show any influence of the rate of the simulated breathing on participants' perceived effort, which was the primary judgment criterion. We did not find any effect of simulated breathing rate on perceived fatigue, cybersickness and embodiment (VR metrics), and preference. However, higher actual breathing rates were observed in the condition with faster simulated breathing.

CONCLUSION: The study did not show the effectiveness of using simulated breathing in VR to manipulate perceived effort during the physical rehabilitation of people with long COVID. Nevertheless, our results suggest that this technique is feasible, as only one participant dropped out due to their symptoms, as most participants had a good appreciation of the system, and reported feeling rather strong embodiment and weak cybersickness.}, } @article {pmid39846976, year = {2024}, author = {Rodríguez-Morán, M and Guerrero-Romero, F and Barragán-Zuñiga, J and Gamboa-Gómez, CI and Weyman-Vela, Y and Arce-Quiñones, M and Simental-Mendía, LE and Martínez-Aguilar, G}, title = {Combined oral supplementation with magnesium plus vitamin D alleviates mild to moderate depressive symptoms related to long-COVID: an open-label randomized, controlled clinical trial.}, journal = {Magnesium research}, volume = {37}, number = {3}, pages = {49-57}, doi = {10.1684/mrh.2024.0535}, pmid = {39846976}, issn = {1952-4021}, mesh = {Humans ; Middle Aged ; Male ; Female ; *Vitamin D/administration & dosage/blood/therapeutic use ; *Dietary Supplements ; *Depression/drug therapy/blood ; Adult ; *Magnesium/administration & dosage/therapeutic use/blood ; Administration, Oral ; COVID-19 ; Vitamin D Deficiency/drug therapy/blood ; Aged ; Magnesium Chloride/administration & dosage/therapeutic use ; }, abstract = {Individuals with long-COVID exhibit a higher frequency of hypomagnesemia, vitamin D deficiency, and depression. Objective. To evaluate the efficacy and safety of oral supplementation with magnesium chloride plus vitamin D in alleviating depressive symptoms related to long-COVID. A total of 60 subjects, aged 52.8±12.6 years, with a diagnosis of hypomagnesemia, vitamin D deficiency, and mild-to-moderate depression (MMD) related to long-COVID, were enrolled in an open-label randomized, controlled clinical trial. Participants were randomly allocated into an intervention group (n=30) that received magnesium chloride (1300 mg) plus vitamin D (4000 IU), or a control group (n=30) that received vitamin D (4000 IU), for four months. Using the Beck Depression Inventory (BDI), diagnosis of MMD was established based on a score of ≥11<30. The primary trial endpoint was improvement in depressive symptoms (BDI <11). Mild adverse events that did not require withdrawal from intervention were documented in six (20.0%) and three (10%) individuals of the intervention and control group, respectively. By comparing baseline vs. final measurements, the BDI score was significantly reduced in individuals in the intervention (28.8±3.7 to 9.2±7.5, p<0.01) and control (28.4±3.8 to 21.6±9.1, p<0.05) group. A total of 22 (73.2%) subjects in the intervention group and 10 (34.5%) in the control group reached a BDI <11, p=0.006. Our results show that, among patients with hypomagnesemia and vitamin D deficiency, combined oral supplementation with magnesium plus vitamin D is effective and safe in alleviating MMD related to long-COVID.}, } @article {pmid39846207, year = {2025}, author = {MacKinnon, C and Castro-Barquero, C and Kontis, A and Patrice, V and Nadarajah, M and Janaudis-Ferreira, T}, title = {Perspectives of Rehabilitation Professionals on Long COVID Interventions to Facilitate Return-to-Work.}, journal = {Canadian journal of occupational therapy. Revue canadienne d'ergotherapie}, volume = {}, number = {}, pages = {84174241312510}, doi = {10.1177/00084174241312510}, pmid = {39846207}, issn = {1911-9828}, abstract = {Background. The severe functional impact of long COVID presents a significant challenge for clients seeking to return to work. Despite emerging clinical management guidelines, long COVID remains a concern in the rehabilitation field. There is a need to establish optimal practices for sustainable rehabilitation paths that enhance the recovery of clients with long COVID, all while understanding the challenges faced by rehabilitation professionals working with this population. Purpose. This study aimed to explore the perspectives of rehabilitation professionals intervening in long COVID rehabilitation with the goal of returning to work. Methods. A qualitative study was conducted involving online semi-structured interviews with rehabilitation professionals in Quebec from public and private sectors across various regions who had experience treating individuals with long COVID. Thematic analysis was employed for data analysis. Findings. Nine rehabilitation professionals participated in the study, yielding five themes: (a) reassessment of RTW goals; (b) education and self-management as primary interventions; (c) gradually reintegrating daily activities and life habits; (d) progression of interventions and dealing with post-exertional malaise (PEM); and (e) challenges in long COVID rehabilitation. Conclusion. Education, gradual activation and self-management appear as central components in supporting patient recovery, however, achieving return to work remains challenging without proper accommodations.}, } @article {pmid39845978, year = {2024}, author = {Guerrera, G and Sambucci, M and Timperi, E and Picozza, M and Misiti, A and Placido, R and Corbisiero, S and D'Orso, S and Termine, A and Fabrizio, C and Gargano, F and Eleuteri, S and Marchioni, L and Bordoni, V and Coppola, L and Iannetta, M and Agrati, C and Borsellino, G and Battistini, L}, title = {Identification of an immunological signature of long COVID syndrome.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1502937}, pmid = {39845978}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *Post-Acute COVID-19 Syndrome ; Female ; Male ; *SARS-CoV-2/immunology ; Middle Aged ; *Adaptive Immunity ; *Immunity, Innate ; Immunophenotyping ; Aged ; Adult ; Biomarkers ; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/immunology ; }, abstract = {INTRODUCTION: Acute COVID-19 infection causes significant alterations in the innate and adaptive immune systems. While most individuals recover naturally, some develop long COVID (LC) syndrome, marked by persistent or new symptoms weeks to months after SARS-CoV-2 infection. Despite its prevalence, there are no clinical tests to distinguish LC patients from those fully recovered. Understanding the immunological basis of LC is essential for improving diagnostic and treatment approaches.

METHODS: We performed deep immunophenotyping and functional assays to examine the immunological profiles of LC patients, individuals with active COVID-19, recovered patients, and healthy donors. This analysis assessed both innate and adaptive immune features, identifying potential biomarkers for LC syndrome. A Binomial Generalized Linear Model (BGLM) was used to pinpoint immune features characterizing LC.

RESULTS: COVID-19 patients exhibited depletion of innate immune cell subsets, including plasmacytoid and conventional dendritic cells, classical, non-classical, and intermediate monocytes, and monocyte-derived inflammatory dendritic cells. Elevated basal inflammation was observed in COVID-19 patients compared to LC patients, whose immune profiles were closer to those of healthy donors and recovered individuals. However, LC patients displayed persistent immune alterations, including reduced T cell subsets (CD4, CD8, Tregs) and switched memory B cells, similar to COVID-19 patients. Through BGLM, a unique adaptive immune signature for LC was identified, featuring memory CD8 and gd T cells with low proliferative capacity and diminished expression of activation and homing receptors.

DISCUSSION: The findings highlight a unique immunological signature associated with LC syndrome, characterized by persistent adaptive immune dysregulation. While LC patients displayed recovery in innate immune profiles comparable to healthy and Recovered individuals, deficits in T cell and memory B cell populations were evident, differentiating LC from full recovery. These findings provide insights into LC pathogenesis and may support the development of diagnostic tools and targeted therapies.}, } @article {pmid39844222, year = {2025}, author = {Glover, J}, title = {The Latest Evidence.}, journal = {The American journal of nursing}, volume = {125}, number = {2}, pages = {13}, doi = {10.1097/AJN.0000000000000010}, pmid = {39844222}, issn = {1538-7488}, } @article {pmid39843672, year = {2025}, author = {Kaufmann, ND and Mazor, KM and Marathe, J and Linas, BP and Fisher, KA}, title = {Primary Care Physicians' Preparedness to Recognize and Evaluate Patients for Long COVID.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {39843672}, issn = {1525-1497}, support = {OT2HL158287/HL/NHLBI NIH HHS/United States ; }, } @article {pmid39843527, year = {2025}, author = {Rajai Firouzabadi, S and Mohammadi, I and Alinejadfard, M and Shafiee, A}, title = {E-cigarettes are not associated with post-acute COVID-19 syndrome among US adults.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {2870}, pmid = {39843527}, issn = {2045-2322}, mesh = {Humans ; Male ; Female ; Adult ; *COVID-19/epidemiology ; Middle Aged ; United States/epidemiology ; *Electronic Nicotine Delivery Systems/statistics & numerical data ; *Post-Acute COVID-19 Syndrome ; Vaping/adverse effects ; SARS-CoV-2/isolation & purification ; Young Adult ; Aged ; Adolescent ; Risk Factors ; Smoking/adverse effects ; Behavioral Risk Factor Surveillance System ; }, abstract = {The COVID-19 pandemic has resulted in many survivors experiencing post-acute COVID-19 syndrome (PCS) with symptoms including fatigue, breathlessness, and cognitive complaints. E-cigarette use has already been associated with increased susceptibility to COVID-19 because of its effects on ACE2 receptor expression and inflammation, raising concern that it might worsen the long-term outcomes of COVID-19, including PCS. While traditional smoking is associated with a higher risk of PCS, the role of e-cigarettes remains unclear due to conflicting evidence. Using 2022 Behavioral Risk Factor Surveillance System (BRFSS) data, this study investigated the association between e-cigarette use and PCS among US adults who tested positive for COVID-19. The final sample included 107,249 adults after the exclusion of respondents with missing information. It analyzed e-cigarette use (never, former, current) and controlled for key covariates such as age, gender, BMI, smoking, and chronic diseases. The results showed that female gender, obesity, current smoking, and a history of depression, asthma, and chronic obstructive pulmonary disease (COPD) were significantly associated with higher odds of PCS. Nevertheless, e-cigarette use was not related significantly to increased odds for PCS (current e-cigarette use: aOR = 1.07, 95 CI: 0.96, 1.20; former e-cigarette use: aOR = 1.03, 95 CI: 0.96, 1.12). The mediation analysis showed no indirect effect of the use of e-cigarettes on PCS via COPD. In conclusion our findings did not reveal an independent or indirect association between PCS with e-cigarette use.}, } @article {pmid39843379, year = {2025}, author = {Wu, S and Luo, Z and Liu, H and Zhu, J and Zhu, Y and Hou, D and Wei, T and Liu, T and Zheng, C and Zhu, Z and Huang, W and Bai, W and Yu, X and Yuan, H and Bao, W and Zhang, M and Niu, X}, title = {Multicentre, multitime, multidimension, prospective follow-up cohort study on patients during the first wave of COVID-19 in China: a study protocol.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e083023}, doi = {10.1136/bmjopen-2023-083023}, pmid = {39843379}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; China/epidemiology ; Prospective Studies ; *SARS-CoV-2 ; Follow-Up Studies ; Magnetic Resonance Imaging ; Multicenter Studies as Topic ; Research Design ; Male ; Neuroimaging ; Adult ; Female ; Biomarkers/blood ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: During the first wave of the COVID-19 outbreak in China, the surge of COVID-19 cases was rapid and drastic. Emerging evidence suggests that beyond the acute phase, patients with COVID-19 may experience a wide range of postacute or long COVID sequelae. However, the mechanism and burden of COVID-19, especially long COVID, have not yet been comprehensively clarified. To fill this knowledge gap, this large prospective follow-up study aims to investigate the short-term and long-term effects of COVID-19, explore the underlying biological mechanism and identify predictive neuroimaging and haematological biomarkers associated with these effects.

METHODS AND ANALYSIS: This multicentre study will recruit patients infected during the first wave of COVID-19 in China and healthy controls (HCs) with no history of COVID-19 infection from nine participating hospitals. Confirmed patients with mild or moderate COVID-19 will complete the following programmes during the acute infection phase and at 3, 12 and 24 months after infection: (a) blood test at the local laboratory, (b) multimodal brain and spine MRI scan and (c) the neuropsychological scales and questionnaires. Similarly, the uninfected HCs will complete the same programmes as the infected group mentioned above at the time of inclusion. At the first time point, 501 participants (418 patients and 83 HCs) from nine recruiting hospitals have been observed. Ultimately, all of these results will be analysed to explore the short-term and long-term effects of COVID-19.

ETHICS AND DISSEMINATION: Ethics approval was granted by Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-013). Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals.

TRIAL REGISTRATION NUMBER: NCT05745805.}, } @article {pmid39842946, year = {2025}, author = {Bartsch, SM and Chin, KL and Strych, U and John, DC and Shah, TD and Bottazzi, ME and O'Shea, KJ and Robertson, M and Weatherwax, C and Heneghan, J and Martinez, MF and Ciciriello, A and Kulkarni, S and Velmurugan, K and Dibbs, A and Scannell, SA and Shen, Y and Nash, D and Hotez, PJ and Lee, BY}, title = {The Current and Future Burden of Long COVID in the United States (U.S.).}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf030}, pmid = {39842946}, issn = {1537-6613}, abstract = {BACKGROUND: Long COVID, which affects an estimated 44.69-48.04 million people in the U.S., is an ongoing public health concern that will continue to grow as SARS-CoV-2 continues to spread.

METHODS: We developed a computational simulation model representing the clinical course, the health effects, and the associated costs of a person with Long COVID.

RESULTS: Simulations show that the average total cost of a Long COVID case can range from $5,084-$11,646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of Long COVID cases could end up costing society at least $2.01-$6.56 billion, employers at least $1.99-$6.49 billion in productivity losses, and third-party payers $21-68.5 million annually (6%-20% probability of developing Long COVID). These cases would accrue 35,808-121,259 QALYs lost and 13,484-45,468 DALYs. Moreover, each year, there may be an additional $698.5 million in total costs, 14,685 QALYs lost, and 5,628 DALYs, if the incidence of COVID is 100 per 10,000 persons (similar to that seen in 2023). Every 10-point increase in COVID incidence results in an additional $365 million in total costs, 5,070 QALYs lost, and 1,900 DALYs each year.

CONCLUSION: The current health and economic burden of Long COVID may already exceed that of a number of other chronic disease and will continue to grow each year as there are more and more COVID-19 cases. This could be a significant drain on businesses, third party payers, the healthcare system, and all of society.}, } @article {pmid39842849, year = {2025}, author = {Nguyen, D and Kavanagh, S and Bowe, S and Tan, E and Moodie, M and Gao, L}, title = {Impact of COVID-19 on hospitalization for heart failure: a perspective from Victoria, Australia.}, journal = {European journal of cardiovascular nursing}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjcn/zvae180}, pmid = {39842849}, issn = {1873-1953}, support = {//Institute for Health Transformation Category 1 Seed Funding Grant/ ; //Deakin University/ ; }, abstract = {AIMS: The COVID-19 pandemic disrupted healthcare systems and possibly impacted the management of heart failure (HF). This study examined the impact of the pandemic on HF hospitalization activities, outcomes, and costs in Victoria, Australia.

METHODS AND RESULTS: Data on HF hospitalizations were acquired from the Victorian Admitted Episodes Dataset. All consecutive patients hospitalized for HF in both public and private hospitals in Victoria between February 2019 and March 2021 were extracted using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification. Data were analysed using descriptive analysis and interrupted time series analysis. A total of 85 564 completed admissions were identified, of which 45 080 were hospitalized in the pre-COVID-19 period and 40 484 were hospitalized in the COVID-19 impacted period. A higher average cost per completed admission in the COVID-19 impacted period was observed, while average length of stay (LOS) was not different between the two periods. It was revealed that monthly total LOS and hospitalization activity cost across all HF admissions dropped at the beginning of the pandemic and continued to decrease until the end of the observation period. However, these changes were not statistically significant.

CONCLUSION: The impacts of COVID-19 on HF hospitalization activities and associated outcomes at the beginning of the pandemic appeared relatively small and were not sustained. Further studies using other data (i.e. linkage data) are required to understand if, or how, the pandemic impacted on HF management in Australia, especially in the long COVID-19 era.}, } @article {pmid39842842, year = {2025}, author = {Lu, Y and Lindaas, A and Izurieta, HS and Cozen, M and Menis, M and Shi, X and Steele, WR and Wernecke, M and Chillarige, Y and Kelman, JA and Forshee, RA}, title = {Lessons Learned From Characterizing Long COVID Among US Medicare Beneficiaries.}, journal = {Pharmacoepidemiology and drug safety}, volume = {34}, number = {2}, pages = {e70101}, doi = {10.1002/pds.70101}, pmid = {39842842}, issn = {1099-1557}, support = {02309-075-075-013007/FD/FDA HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; *COVID-19/epidemiology ; *Medicare/statistics & numerical data ; Aged ; Retrospective Studies ; Male ; Female ; Aged, 80 and over ; *Fee-for-Service Plans/statistics & numerical data ; Nursing Homes/statistics & numerical data ; Incidence ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: To characterize long-term effects of COVID-19 among older adults (aged ≥ 65 years).

METHODS: This retrospective descriptive study utilized Medicare Fee-for-Service beneficiaries' claims to characterize post-COVID condition diagnosis code usage, long COVID (defined as post-COVID condition diagnoses made ≥ 28 days after an initial COVID-19 diagnosis) incidence, patient demographics, and concurrent diagnoses.

RESULTS: During April 1, 2020 to May 21, 2022, 193 691 (0.6%) of 31 847 927 Medicare beneficiaries were diagnosed with post-COVID conditions using ICD-10-CM diagnosis codes U09.9 and B94.8, regardless of prior COVID-19 diagnosis. Post-COVID condition diagnosis rate was higher among nursing home residents (18.7 per 1000 person-years) than community-dwelling beneficiaries (2.8). Among community-dwelling beneficiaries with a post-COVID condition diagnosis, 17.5% did not have any prior COVID-19 diagnosis code U07.1 recorded. Among beneficiaries with COVID-19 diagnosis, there were no significant sex, age, or race/ethnicity differences between those with post-COVID conditions ≥ 28 days after COVID-19 (i.e., long COVID) and those without post-COVID conditions. Certain myopathies and interstitial pulmonary disease codes were disproportionately present concurrently with long COVID compared to COVID-19.

CONCLUSIONS: In this large study of 32 million Medicare beneficiaries, we found approximately 194 000 post-COVID condition diagnoses. Post-COVID condition diagnosis rate was higher among nursing home residents, highlighting the substantial burden of COVID-19 in this vulnerable population. Community-dwelling beneficiaries were less likely to seek medical care for COVID-19 events than nursing home residents, which may suggest differences in COVID-19 severity and respiratory disease detection between these populations. Long COVID risk after COVID-19 infection may be similar across demographic groups.}, } @article {pmid39841477, year = {2025}, author = {Shah, DP and Thaweethai, T and Karlson, EW and Bonilla, H and Horne, BD and Mullington, JM and Wisnivesky, JP and Hornig, M and Shinnick, DJ and Klein, JD and Erdmann, NB and Brosnahan, SB and Lee-Iannotti, JK and Metz, TD and Maughan, C and Ofotokun, I and Reeder, HT and Stiles, LE and Shaukat, A and Hess, R and Ashktorab, H and Bartram, L and Bassett, IV and Becker, JH and Brim, H and Charney, AW and Chopra, T and Clifton, RG and Deeks, SG and Erlandson, KM and Fierer, DS and Flaherman, VJ and Fonseca, V and Gander, JC and Hodder, SL and Jacoby, VL and Kotini-Shah, P and Krishnan, JA and Kumar, A and Levy, BD and Lieberman, D and Lin, JJ and Martin, JN and McComsey, GA and Moukabary, T and Okumura, MJ and Peluso, MJ and Rosen, CJ and Saade, G and Shah, PK and Sherif, ZA and Taylor, BS and Tuttle, KR and Urdaneta, AE and Wallick, JA and Wiley, Z and Zhang, D and Horwitz, LI and Foulkes, AS and Singer, NG and , }, title = {Sex Differences in Long COVID.}, journal = {JAMA network open}, volume = {8}, number = {1}, pages = {e2455430}, doi = {10.1001/jamanetworkopen.2024.55430}, pmid = {39841477}, issn = {2574-3805}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; Middle Aged ; Adult ; *SARS-CoV-2 ; Sex Factors ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Aged ; Risk Factors ; Prospective Studies ; }, abstract = {IMPORTANCE: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain.

OBJECTIVE: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection.

This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection.

EXPOSURE: Self-reported sex (male, female) assigned at birth.

MAIN OUTCOMES AND MEASURES: Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity.

RESULTS: Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants.

CONCLUSIONS AND RELEVANCE: In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID.}, } @article {pmid39841332, year = {2025}, author = {Hira, R and Baker, JR and Siddiqui, T and Patel, A and Valani, FGA and Lloyd, MG and Floras, JS and Morillo, CA and Sheldon, RS and Raj, SR and , }, title = {Attenuated cardiac autonomic function in patients with long-COVID with impaired orthostatic hemodynamics.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {}, number = {}, pages = {}, pmid = {39841332}, issn = {1619-1560}, support = {G4A- 177741/CAPMC/CIHR/Canada ; NIH UL1-TR000445//Vanderbilt Institute for Clinical and Translational Research/ ; }, abstract = {PURPOSE: Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes.

METHODS: Patients with long-COVID (n = 94; F = 76; 42 years [36, 53 years] with initial orthostatic hypotension: n = 40; F = 32; 49 years [39, 57 years]; postural orthostatic tachycardia syndrome: n = 29; F = 26; 39 years [33, 47 years]; or no abnormalities: n = 25; F = 18; 42 years [35, 49 years]), and healthy controls (n = 33; F = 25; 49 years [30, 62 years]) completed a 10-min active stand with beat-to-beat hemodynamics. Heart rate variability, blood pressure variability, and baroreflex sensitivity were calculated as indirect measures of cardiovascular autonomic health. Continuous data (median [95% confidence interval]) were analyzed with Mann-Whitney U tests or Kruskal-Wallis tests with Dunn's corrections.

RESULTS: Patients with long-COVID had lower upright high frequency heart rate variability (p = 0.04) and low frequency blood pressure variability (p = 0.001) than controls. Patients with initial orthostatic hypotension had lower supine baroreflex sensitivity compared with patients without abnormalities (p = 0.01), and lower supine baroreflex sensitivity (p = 0.001) and high frequency heart rate variability (p = 0.03) than patients with postural orthostatic tachycardia syndrome. Patients with postural orthostatic tachycardia syndrome had lower upright high frequency heart rate variability (p < 0.001) and baroreflex sensitivity (p < 0.001) compared with patients without abnormalities and lower upright low frequency blood pressure variability (p = 0.04) compared with controls.

CONCLUSIONS: Patients with long-COVID have attenuated cardiac autonomic function. Patients with initial orthostatic hypotension have lower supine baroreflex sensitivity. Patients with postural orthostatic tachycardia syndrome have lower upright vascular sympathetic and cardiac parasympathetic modulation. Long-COVID subgroups do not present with homogeneous pathophysiology, necessitating targeted treatment strategies.}, } @article {pmid39840178, year = {2024}, author = {Sarkar, A and Speiser, E and Dara, S and Ogedegbe, C and Chinnery, P and Estanbouli, MT and Kasselman, L and Kligler, B and Gourna Paleoudis, E and Parulekar, M}, title = {The Feasibility of Omega-3 Supplementation Compared to Placebo in the Management of Long COVID Symptoms Among Healthcare Workers: A Randomized Controlled Trial.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76148}, pmid = {39840178}, issn = {2168-8184}, abstract = {BACKGROUND: COVID-19 is known to cause significant multisystem inflammatory responses, leading to symptoms beyond the acute phase of illness. These "long COVID" symptoms affect quality of life and interfere with daily activities. This pilot study looks at the feasibility, tolerability, and safety of omega-3 (docosahexaenoic acid+eicosapentaenoic acid, EPA) among healthcare workers with long COVID symptoms in New Jersey.

METHODS:  This double-blind, randomized-controlled pilot trial used self-administered omega-3 vs. placebo for 12 weeks in healthcare workers. The enrollment period was from October 2021 to March 2023. Participants were monitored weekly for compliance and adverse effects. They completed the Symptoms and Quality of Life survey biweekly. Baseline and week-12 blood test for omega-3 levels and arachidonic acid (AA):EPA ratio was also measured and analyzed. Descriptive statistics were calculated for all variables at 12 weeks. An independent sample t-test was conducted to compare the ages of the treatment groups. Fisher's exact tests were conducted on each outcome by the treatment arm. No adjustments for multiple testing were included; therefore, significance was set at p ≤ 0.05. Analyses were conducted using R version 4.3.3 (R Core Team, Vienna, Austria).

RESULTS:  Thirty-two healthcare workers were recruited, and 18 completed the study. Feasibility was assessed based on enrollment and compliance with the study protocol. There was no significant difference in age between the placebo and treatment groups. The intervention group did not show significant improvement in the long COVID symptoms: shortness of breath (p = 0.39), cough (p = 0.76), fatigue (p = 0.57), lack of taste (p = 0.10), and lack of smell (p = 0.10). In the placebo group, baseline average omega-3 and AA:EPA ratio were 4.09 (standard deviation, SD = 0.85) and 23.9 (SD = 13.4), respectively, and week-12 omega-3 and AA:EPA ratio were 4.46 (SD = 0.95) and 20.8 (SD = 6.0), respectively. For the supplement group, baseline average omega 3 and AA:EPA ratio were 3.75 (SD = 0.48) and 23.1 (SD = 8.3), respectively, and week-12 omega-3 and AA:EPA ratio were 5.97 (SD = 1.93) and 11.8 (SD = 14.0), respectively. One supplement-treated participant and five placebo-treated participants experienced adverse events. No serious adverse events were reported.

CONCLUSIONS:  This pilot study successfully demonstrated the feasibility, safety, and tolerability of using omega-3 supplements for the treatment of long COVID syndrome. The study results did not show statistically significant improvement in the long COVID symptoms. The mean difference in the AA:EPA ratio in the placebo vs. supplement group showed a pronounced decline in inflammatory markers in the supplement group. However, our study did not show a connection between the decreased inflammatory markers and clinical symptoms. We may need a longer follow-up to understand the possible clinical benefits of the decreased AA:EPA ratio.}, } @article {pmid39839604, year = {2024}, author = {Nava, R and Benatti, B and Girone, N and Macellaro, M and Pellicioli, C and Maggioni, L and Marcatili, M and Dell'Osso, B and Clerici, M}, title = {Assessing the Fear of Covid-19 in Psychiatric Patients: Results from an Italian Multicentric Study.}, journal = {Clinical neuropsychiatry}, volume = {21}, number = {6}, pages = {529-537}, pmid = {39839604}, issn = {2385-0787}, abstract = {OBJECTIVE: Even though the COVID-19 emergency has concluded, its consequences are still relevant. Recent evidence suggests that a significant proportion of individuals experience persistent symptoms long after the initial infection has resolved, classified as "Long COVID" condition. Fear of COVID-19 increases anxiety and stress levels in healthy individuals and exacerbates the symptoms of those with pre-existing psychiatric disorders; therefore understanding the impact of the pandemic on psychiatric disorders remains of utmost importance. The present study aimed at assessing the prevalence and predictive factors of fear of COVID-19 in a sample of patients with different psychiatric conditions.

METHOD: A sample of 269 psychiatric patients were recruited from two different tertiary clinics in Italy and assessed with the Fear of COVID-19 Scale (FCV-19S). In order to compare patients with a significant fear of COVID-19 or without (Fear+ vs. Fear-) and to identify the main features in terms of clinical dimension, exploratory and predictive analysis were performed.

RESULTS: Female gender, age at illness onset, and insight levels emerged as positive predictors of FCV-19S. Conversely, current substance abuse emerged as a negative predictor of fear levels. Moreover, significantly lower FCV-19S scores were observed in patients with a diagnosis of schizophrenia spectrum disorders.

CONCLUSIONS: Specific sociodemographic and clinical factors predicted higher levels of fear of COVID-19 in psychiatric patients. Further studies are warranted to determine the potential long-term consequences of the COVID-19 impact on mental health.}, } @article {pmid39839305, year = {2024}, author = {Gonzalez Aleman, G and Vavougios, GD and Tartaglia, C and Uvais, NA and Guekht, A and Hosseini, AA and Lo Re, V and Ferreccio, C and D'Avossa, G and Zamponi, HP and Figueredo Aguiar, M and Yecora, A and Ul Haq Katshu, MZ and Stavrou, VT and Boutlas, S and Gourgoulianis, KI and Botero, C and González Insúa, F and Perez-Lloret, S and Zinchuk, M and Gersamija, A and Popova, S and Bryzgalova, Y and Sviatskaya, E and Russelli, G and Avorio, F and Wang, S and Edison, P and Niimi, Y and Sohrabi, HR and Mukaetova Ladinska, EB and Neidre, D and de Erausquin, GA}, title = {Age-dependent phenotypes of cognitive impairment as sequelae of SARS-CoV-2 infection.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1432357}, pmid = {39839305}, issn = {1663-4365}, abstract = {Cognitive changes associated with PASC may not be uniform across populations. We conducted individual-level pooled analyses and meta-analyses of cognitive assessments from eight prospective cohorts, comprising 2,105 patients and 1,432 controls from Argentina, Canada, Chile, Greece, India, Italy, Russia, and the UK. The meta-analysis found no differences by country of origin. The profile and severity of cognitive impairment varied by age, with mild attentional impairment observed in young and middle-aged adults, but memory, language, and executive function impairment in older adults. The risk of moderate to severe impairment doubled in older adults. Moderately severe or severe impairment was significantly associated with infection diagnoses (chi-square = 26.57, p ≤ 0.0001) and the severity of anosmia (chi-square = 31.81, p ≤ 0.0001). We found distinct age-related phenotypes of cognitive impairment in patients recovering from COVID-19. We identified the severity of acute illness and the presence of olfactory dysfunction as the primary predictors of dementia-like impairment in older adults.}, } @article {pmid39838139, year = {2025}, author = {Ruiz de Lazcano, A and Pérez-Núñez, P and Pallarès-Sastre, M and García-Sanchoyerto, M and García, I and Amayra, I}, title = {Long-COVID and postural orthostatic tachycardia syndrome: a preliminary comparison of neuropsychological performance.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {}, number = {}, pages = {}, pmid = {39838139}, issn = {1619-1560}, abstract = {PURPOSE: The aim of the study is to analyze and compare the cognitive profile between 59 patients with long-COVID [LC; 30 of them with and 29 without a positive coronavirus disease 2019 (COVID-19) confirmatory test] and 31 patients with postural orthostatic tachycardia syndrome (POTS) and a matched group of 39 healthy control participants.

METHODS: Participants were examined on a battery of neuropsychological tests, including verbal memory, visuospatial abilities, attention, processing speed, verbal fluency, working memory, and visual memory. Anxious-depressive symptomatology was also analyzed and then controlled for possible influence on cognitive performance.

RESULTS: Patients with LC and POTS showed significantly lower performance compared with healthy peers. Differences on anxious and depressive symptoms were also found between the clinical and control groups, resulting in LC without a positive confirmatory test group exhibiting the highest rates of anxious symptoms. After controlling the effects of anxious-depressive symptomatology, the differences were eliminated for some of the cognitive variables, but additional differences were found between patients with LC and POTS after post hoc analysis.

CONCLUSIONS: Findings from the present study contribute toward the reinforcement of the evidence on cognitive alterations associated with LC and POTS. Anxious-depressive symptomatology has to be considered in both clinical groups since it could be affecting cognitive performance.}, } @article {pmid39838062, year = {2025}, author = {Garcia-Molina, G and Guzenko, D and DeFranco, S and Aloia, MS and Mills, R and Mushtaq, F and Somers, VK and Van Cauter, E}, title = {Sleep and cardiorespiratory function assessed by a smart bed over 10 weeks post COVID-19 infection.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {2724}, pmid = {39838062}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/physiopathology/epidemiology/complications ; Male ; Middle Aged ; Female ; *Sleep/physiology ; Adult ; *SARS-CoV-2/isolation & purification ; *Heart Rate/physiology ; Bradycardia/physiopathology ; Beds ; Respiratory Rate ; }, abstract = {Inadequate information exists regarding physiological changes post-COVID-19 infection. We used smart beds to record biometric data following COVID-19 infection in nonhospitalized patients. Recordings of daily biometric signals over 14 weeks in 59 COVID-positive participants' homes in 2020 were compared with the same participants' data from 2019. Participants completed a survey of demographic information, health conditions, COVID exposure and testing, and symptom prevalence/subjective severity. Mean age was 47.5 years (standard deviation [SD] 9.5), mean body mass index was 30.1 kg/m[2] (SD 7.1), and 46% were men. During acute infection, 64% exhibited 5-6 h increased sleep duration, 51% had increased movement, and 64% had increased breathing rate (BR). Nearly 34% had paradoxical bradycardia (decreased heart rate by ~ 10 BPM concomitant with elevated BR and/or fever), with more-severe symptoms. Smart beds can detect physiological changes during COVID-19. A subtype of acute response (paradoxical bradycardia) may predict delay recovery from COVID-19.}, } @article {pmid39837753, year = {2025}, author = {Li, S and Dong, W and Dai, B and Wang, W and Tan, W}, title = {Telerehabilitation in patients with long COVID-19 syndrome.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2025.01.010}, pmid = {39837753}, issn = {1879-0828}, } @article {pmid39837387, year = {2025}, author = {Mendes, S and Guimarães, LC and de Oliveira, LC and Costa, PAC and da Silva, NJA and Pereira, GSAP and Fernandez, CC and Figueiredo, MM and Dos Santos, RAS and Teixeira, MM and Costa, VV and Guimarães, PPG and Frézard, F}, title = {Intranasal liposomal remdesivir induces SARS-CoV-2 clearance in K18-hACE2 mice and ensures survival.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jconrel.2025.01.044}, pmid = {39837387}, issn = {1873-4995}, abstract = {A huge challenge after the emergence of COVID-19 has been the discovery of effective antiviral drugs. Although remdesivir (RDV) emerged as one of the most promising drugs, its pharmaceutical formulation Veklury® is limited by moderate efficacy, high toxicity and need for parenteral administration. The aim of the present work was to develop a liposomal formulation of RDV for pulmonary administration and evaluate its efficacy in models of COVID-19. Liposomal RDV nanoformulation (LRDV) was selected based on high drug encapsulation efficiency, sustained drug release property and high in vitro selectivity index. A pharmacokinetic study of intranasal LRDV in mice demonstrated effective delivery of the drug to the lungs. LRDV was then evaluated for its efficacy in SARS-CoV-2-infected K18-hACE2 mice after repeated intranasal administration at 10 mg/kg/bid for 5 days. Veklury® given intraperitoneally at 20 mg/kg/bid was used for comparison. Mice receiving LRDV remained alive up to 15 days post-infection (dpi). On the other hand, the control groups receiving PBS and empty liposomes showed 100 % death at 6 dpi and the Veklury® group had 62.5 % death at 8 dpi. Intranasal LRDV also promoted a strong reduction in viral loads in the brain and lungs of mice and prevented the inflammatory response induced by SARS-CoV-2 in the lungs. This is in contrast with Veklury®, which did not significantly reduce the viral titer in the brain and was poorly effective in preventing the inflammatory response in the lungs. Intranasal LRDV emerges as a promising therapeutic strategy for COVID-19, including "Long COVID".}, } @article {pmid39836023, year = {2025}, author = {Baig, AM and Rosko, S and Jaeger, B and Gerlach, J}, title = {Strategic Inhibition of CHRM Autoantibodies: Molecular Insights and Therapeutic Potentials in Long COVID.}, journal = {Journal of medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jmedchem.4c00691}, pmid = {39836023}, issn = {1520-4804}, abstract = {In addition to the conventional symptoms reported for COVID-19, it is becoming increasingly clear that patients with long COVID are exhibiting new symptoms due to the emergence of autoantibodies against G-protein-coupled receptors, among which human muscarinic cholinergic receptors (CHRMs) have been prominently reported. With a chronic condition such as long COVID, additional symptoms caused by anti-CHRM autoantibodies (AAbs) have proven to be an added burden on these patients. The origins of these AAbs, their interactions with, and effects on the function of neural and non-neural cells within the nervous system have remained unknown. Furthermore, the specific symptom complex to which they contribute has not been clearly understood. In this context, we address these issues here and suggest methods to combat the autoantibodies that contribute to neurological symptoms in long COVID.}, } @article {pmid39835117, year = {2024}, author = {Galipeau, Y and Cooper, C and Langlois, MA}, title = {Autoantibodies in COVID-19: implications for disease severity and clinical outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1509289}, doi = {10.3389/fimmu.2024.1509289}, pmid = {39835117}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology ; *SARS-CoV-2/immunology ; *Severity of Illness Index ; Autoimmunity ; Autoimmune Diseases/immunology ; }, abstract = {Few pathogens have historically been subjected to as intense scientific and clinical scrutiny as SARS-CoV-2. The genetic, immunological, and environmental factors influencing disease severity and post-infection clinical outcomes, known as correlates of immunity, remain largely undefined. Clinical outcomes of SARS-CoV-2 infection vary widely, ranging from asymptomatic cases to those with life-threatening COVID-19 symptoms. While most infected individuals return to their former health and fitness within a few weeks, some develop debilitating chronic symptoms, referred to as long-COVID. Autoimmune responses have been proposed as one of the factors influencing long-COVID and the severity of SARS-CoV-2 infection. The association between viral infections and autoimmune pathologies is not new. Viruses such as Epstein-Barr virus and cytomegalovirus, among others, have been shown to induce the production of autoantibodies and the onset of autoimmune conditions. Given the extensive literature on SARS-CoV-2, here we review current evidence on SARS-CoV-2-induced autoimmune pathologies, with a focus on autoantibodies. We closely examine mechanisms driving autoantibody production, particularly their connection with disease severity and long-COVID.}, } @article {pmid39834716, year = {2025}, author = {Gharibzadeh, S and Routen, A and Razieh, C and Zaccardi, F and Lawson, C and Gillies, C and Heller, S and Davies, M and Atkins, H and Bain, SC and Lone, NL and Poinasamy, K and Peto, T and Robertson, E and Young, B and Johnston, D and Quint, J and Valabhji, J and Ismail, K and Marks, M and Horsley, A and Docherty, A and Harrison, E and Chalmers, J and Ho, LP and Raman, B and Brightling, C and Elneima, O and Evans, R and Greening, N and Harris, VC and Houchen-Wolloff, L and Sereno, M and Shikotra, A and Singapuri, A and Wain, L and Langenberg, C and Dennis, J and Petrie, J and Sattar, N and Leavy, O and Richardson, M and Saunders, RM and McArdle, A and McASuley, H and Yates, T and Khunti, K and , }, title = {Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {103005}, doi = {10.1016/j.eclinm.2024.103005}, pmid = {39834716}, issn = {2589-5370}, abstract = {BACKGROUND: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.

METHODS: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions.

FINDINGS: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions.

INTERPRETATION: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes.

FUNDING: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).}, } @article {pmid39832327, year = {2024}, author = {Ramírez-García, SA and Hernández-Osorio, LA and Montero-Toledo, E}, title = {Reply to the letter "New perspectives in the management of SARS-CoV-2 Pirola variants and the development of long COVID syndrome: anti-Ro52/TRIM21 antibodies and qRT-PCR".}, journal = {Gaceta medica de Mexico}, volume = {160}, number = {4}, pages = {452-453}, doi = {10.24875/GMM.M24000923}, pmid = {39832327}, issn = {0016-3813}, } @article {pmid39832320, year = {2024}, author = {Rabadán-Martínez, CE}, title = {New perspectives in the management of SARS-CoV-2 Pirola variants and the development of long COVID syndrome: anti-Ro52/TRIM21 antibodies and qRT-PC.}, journal = {Gaceta medica de Mexico}, volume = {160}, number = {4}, pages = {450-451}, doi = {10.24875/GMM.M24000922}, pmid = {39832320}, issn = {0016-3813}, } @article {pmid39832242, year = {2024}, author = {Ozkan, MB and Ozsahin, A and Emre, N and Edirne, T and Kınacı Çimen, Y}, title = {Ongoing post-COVID-19 symptoms and complaints among healthcare professionals.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {12}, pages = {1846-1854}, doi = {10.3855/jidc.19368}, pmid = {39832242}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Male ; Female ; *Health Personnel/statistics & numerical data ; Adult ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fatigue/etiology ; Young Adult ; }, abstract = {INTRODUCTION: Post-COVID-19 syndrome refers to the occurrence of symptoms lasting more than 4 weeks in individuals who have recovered from COVID-19. This study aims to investigate the post-COVID-19 symptoms in healthcare professionals.

METHODOLOGY: This descriptive study included 166 healthcare professionals who had tested positive for COVID-19 via PCR at least four weeks prior and subsequently presented to the Family Medicine Clinic at Pamukkale University Training and Research Hospital. Participants` demographic data, medical history, COVID-19 history and ongoing or newly emerged complaints and symptoms were evaluated, and physical examinations were carried out and recorded on a patient information form. Blood tests were conducted, and the results were analyzed.

RESULTS: The most common post-COVID-19 symptoms and complaints observed in our study were difficulty in performing daily activities (32.5%; n = 54), fatigue (26.5%; n = 44), forgetfulness (25.9%; n = 43) and weakness (24.1%; n = 40), respectively. Smoking, alcohol use, hospitalization, the need for oxygen support and having comorbidities such as asthma, diabetes, hypertension and rheumatism were found to be associated with various post-acute symptoms. Post-acute symptoms were most frequently observed in individuals vaccinated with Sinovac (38.5%), followed by those who were unvaccinated (35.7%). Least symptoms were seen in individuals vaccinated with only Biontech (15.4%).

CONCLUSIONS: The most common post-COVID-19 symptoms observed in our study were difficulty in performing daily activities, fatigue, forgetfulness and weakness. Having comorbidities was found to be associated with various post-COVID-19 symptoms.}, } @article {pmid39832090, year = {2025}, author = {Niewiadomski, P and Ortega-Ortega, M and Łyszczarz, B}, title = {Productivity Losses due to Health Problems Arising from COVID-19 Pandemic: A Systematic Review of Population-Level Studies Worldwide.}, journal = {Applied health economics and health policy}, volume = {}, number = {}, pages = {}, pmid = {39832090}, issn = {1179-1896}, support = {2022/47/B/HS4/00081//Narodowe Centrum Nauki/ ; 2022/47/B/HS4/00081//Narodowe Centrum Nauki/ ; }, abstract = {AIM: To systematically review the evidence on productivity losses due to health problems arising from the COVID-19 pandemic based on evidence from population-level studies.

METHODS: Following PRISMA statement, we conducted a systematic review using Medline, Embase, Scopus, Web of Science, EconLit, WHO COVID-19 Research and EuropePMC databases and a grey literature search. We included population-level studies using secondary data and qualitatively assessed eligible studies. For a quantitative cross-study comparison, we calculated losses in 2020 international dollars and as a share of gross domestic product. PROSPERO registration number: CRD42023478059.

RESULTS: Thirty-eight studies were eligible for review, most of which reported losses in high-income countries and the European region. COVID-19 was a focus of 33 studies while 3 studies investigated losses from both long COVID and excess mortality. The Human Capital Approach dominated (30 studies) and no study used the Friction Cost Approach. Most studies (84%) reported on premature mortality losses and a quarter provided estimates of losses due to absenteeism. Of the 33 studies eligible for quantitative comparison, we found that the productivity losses ranged from 0 to 2.1% of gross domestic product; the greatest losses were in the high-income countries and for those aged 40-59 years; and losses among men contributed to around 3/4 of the total burden.

CONCLUSION: The available evidence on the topic is limited, particularly considering the methodological approaches used. Thus, more research is needed to reach a more comprehensive understanding of economy-level productivity losses resulting from the recent COVID-19 pandemic.}, } @article {pmid39830383, year = {2024}, author = {Liu, W and Feng, Q and Yuan, X and Lu, C and Wang, S and Yuan, Y}, title = {Diagnostic value of lung function tests in long COVID: analysis of positive bronchial provocation test outcomes.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1512658}, doi = {10.3389/fmed.2024.1512658}, pmid = {39830383}, issn = {2296-858X}, abstract = {BACKGROUND: Long COVID patients are prone to bronchial hyperresponsiveness and respiratory symptoms like coughing and breathing difficulties, often with positive bronchial provocation test (BPT) results.

OBJECTIVE: This study aims to evaluate the diagnostic value of various lung function tests in patients with long-term COVID-19, explicitly focusing on positive BPT outcomes.

METHODS: Our study analyzed the BPT outcomes and various pulmonary function parameters of all 9,406 COVID-19 patients who met the inclusion criteria and visited our hospital between February 24, 2022, and April 28, 2024. Key indicators included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and single-breath diffusing capacity for carbon monoxide (DLCOc SB). A logistic regression model was employed to identify factors influencing positive BPT results, while the receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of these indicators.

RESULTS: A total of 4211 valid samples were analyzed, with 3388 patients (80.46%) testing positive for BPT. Significant differences were observed between positive and negative groups regarding age, gender, smoking status (all P < 0.05), and specific lung function indicators, including FVC, FEV1/FVC ratio, maximum of vital capacity (VC max), and DLCOc SB (all P < 0.001). Logistic regression identified age, MEF50, and DLCOc SB as independent factors influencing positive BPT results. The area under the ROC curve for all assessed factors was <0.700, indicating limited diagnostic value.

CONCLUSION: Age, the small airway function indicator MEF50, and the pulmonary diffusion function indicator DLCOc SB are independent influencing factors for BPT positivity in long-term COVID patients. However, baseline data and lung function indicators have limited utility for diagnosing positive BPT in this population, highlighting the complex nature of post-COVID respiratory symptoms.}, } @article {pmid39830235, year = {2025}, author = {Hou, Y and Gu, T and Ni, Z and Shi, X and Ranney, ML and Mukherjee, B}, title = {Global Prevalence of Long COVID, its Subtypes and Risk factors: An Updated Systematic Review and Meta-Analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.01.24319384}, pmid = {39830235}, abstract = {IMPORTANCE: Updated knowledge regarding the global prevalence of long COVID (or post-COVID-19 condition), its subtypes, risk factors, and variations across different follow-up durations and geographical regions is necessary for informed public health recommendations and healthcare delivery.

OBJECTIVE: The primary objective of this systematic review is to evaluate the global prevalence of long COVID and its subtypes and symptoms in individuals with confirmed COVID-19 diagnosis, while the secondary objective is to assess risk factors for long COVID in the same population.

DATA SOURCES: Studies on long COVID published from July 5, 2021, to May 29, 2024, searched from PubMed, Embase, and Web of Science were used for this systematic review. Supplemental updates to the original search period were made.

STUDY SELECTION: There were four inclusion criteria: (1) human study population with confirmed COVID-19 diagnosis; (2) appropriate index diagnosis date; (3) outcome must include either prevalence, risk factors, duration, or symptoms of long COVID; and (4) follow-up time of at least two months after the index date. The exclusion criteria were: (1) non-human study population; (1) case studies or reviews; (2) studies with imaging, molecular, and/or cellular testing as primary results; (3) studies with specific populations such as healthcare workers, residents of nursing homes, and/or those living in long-term care facilities; and (4) studies that did not meet the sample size threshold needed to estimate overall prevalence with margin of error of 0.05.

DATA EXTRACTION AND SYNTHESIS: Two screeners independently performed screenings and data extraction, and decision conflicts were collectively resolved. The data were pooled using a random-effects meta-analysis framework with a DerSimonian-Laird inverse variance weighted estimator.

MAIN OUTCOMES AND MEASURES: The primary estimand (target population parameter of interest) was the prevalence of long COVID and its subtypes among individuals with confirmed COVID-19 diagnoses, and the secondary estimand was effect sizes corresponding to ten common risk factors of long COVID in the same population.

RESULTS: A total of 442 studies were included in this mega-systematic review, and 429 were meta-analyzed for various endpoints, avoiding duplicate estimates from the same study. Of the 442 studies, 17.9% of the studies have a high risk of bias. Heterogeneity is evident among meta-analyzed studies, where the I [2] statistic is nearly 100% in studies that estimate overall prevalence. Global estimated pooled prevalence of long COVID was 36% among COVID-19 positive individuals (95% confidence interval [CI] 33%-40%) estimated from 144 studies. Geographical variation was observed in the estimated pooled prevalence of long COVID: Asia at 35% (95% CI 25%-46%), Europe at 39% (95% CI 31%-48%), North America at 30% (95% CI 24%-38%), and South America at 51% (95% CI 35%-66%). Stratifying by follow-up duration, the estimated pooled prevalence for individuals with longer follow-up periods of 1 to 2 years (47% [95% CI 37%-57%]) compared to those with follow-up times of less than 1 year (35% [95% CI 31%-39%]) had overlapping CI and were therefore not statistically distinguishable. Top five most prevalent long COVID subtypes among COVID-19 positive cases were respiratory at 20% (95% CI 14%-28%) estimated from 31 studies, general fatigue at 20% (95% CI 18%-23%) estimated from 121 studies, psychological at 18% (95% CI 11%-28%) estimated from 10 studies, neurological at 16% (95% CI 8%-30%) estimated from 23 studies, and dermatological at 12% (95% CI 8%-17%) estimated from 10 studies. The most common symptom based on estimated prevalence was memory problems estimated at 11% (95% CI 7%-19%) meta-analyzed from 12 studies. The three strongest risk factors for long COVID were being unvaccinated for COVID-19, pre-existing comorbidity, and female sex. Individuals with any of these risk factors had higher odds of having long COVID with pooled estimated odds ratios of 2.34 (95% CI 1.49-3.67) meta-analyzed from 6 studies, 1.59 (95% CI 1.28-1.97) from 13 studies, and 1.55 (95% CI 1.25-1.92) from 22 studies, respectively.

CONCLUSIONS AND RELEVANCE: This study shows long COVID is globally prevalent in the COVID-19 positive population with highly varying estimates. The prevalence of long COVID persists over extended follow-up, with a high burden of symptoms 1 to 2 years post-infection. Our findings highlight long COVID and its subtypes as a continuing health challenge worldwide. The heterogeneity of the estimates across populations and geographical regions argues for the need for carefully designed follow-up with representative studies across the world.

KEY POINTS: Question: What are the prevalence and patterns of long COVID and its subtypes, and what are the risk factors of long COVID?Results: Meta-analysis of 429 studies published from 2021-2024 estimated a pooled global long COVID prevalence of 36% in COVID-19 positive individuals. Variations in geographical regions showed that South America had the highest pooled prevalence of 51% (95% CI: 35%-66%), and the prevalence does not seem to diminish with extended follow-up (less than 1 year: 35%, 95% CI: 31%-39% vs. 1 to 2 years: 47%, 95% CI: 37%-57%). The estimated pooled prevalence of eight major long COVID subtypes in COVID-19 positive individuals were 20% (respiratory), 20% (general fatigue), 18% (psychological), 16% (neurological), 12% (dermatological), 10% (cardiovascular), 9% (musculoskeletal) and 5% (gastrointestinal).Meaning: Quantitative evidence shows a persistent prevalence of long COVID globally, with a significant burden of symptoms 1 to 2 years post-infection, underscoring the need for having accurate and standardized diagnostic tests and biomarkers for long COVID, a better understanding of the physiology of the condition, its treatment, and its potential effect on healthcare needs and workforce participation. The heterogeneity and wide range of the prevalence estimates call for representative samples in well-designed follow-up studies of long COVID across the world.}, } @article {pmid39826380, year = {2025}, author = {Hu, LY and Cai, AQ and Li, B and Sun, YQ and Li, Z and Liu, JP and Cao, HJ}, title = {Prevalence and risk factors for long COVID in China: A systematic review and meta-analysis of observational studies.}, journal = {Journal of infection and public health}, volume = {18}, number = {3}, pages = {102652}, doi = {10.1016/j.jiph.2025.102652}, pmid = {39826380}, issn = {1876-035X}, abstract = {BACKGROUND: With the outbreak of COVID-19 in China, a large number of COVID-19 patients are at risk of long COVID after recovery. The purpose of our research is to systematically review the existing clinical studies to understand the current prevalence and related risk factors of long COVID in COVID-19 patients in China.

METHODS: The protocol of this systematic review was registered on PROSPERO (CRD42024519375). We searched six electronic databases from 1st January 2020-1st March 2024. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included studies was evaluated by AHRQ and NOS. The meta-analysis was performed by R software 4.2.3 to derive the prevalence of long COVID and risk factors.

RESULTS: Overall, 50 studies with 65880 participants were included. The results showed that the prevalence of long COVID (with at least one symptom) among the COVID-19 patients was approximately 50 % (95 %Confidence Interval (CI) 42-58 %) in China. Although we conducted meta-regression and subgroup analysis, the heterogeneity of the study was high. But the Omicron BA.2 variant had a statistically significant effect on the prevalence of long COVID (P = 0.0004). The three most common symptoms of long COVID were fatigue (0.33, 95 %CI 0.28-0.39), cognitive decline (0.30, 95 %CI 0.14-0.46) and shortness of breath (0.29, 95 %CI 0.15-0.43). Patients with severe acute phase of COVID-19 (Odds Ratio (OR) 1.57, 95 % CI 1.39-1.77), combined 2 comorbidities (OR 1.80, 95 % CI 1.40-2.32), combined 3 comorbidities (OR 2.13, 95 % CI 1.64-2.77), advanced age (OR 1.02, 95 % CI 1.01-1.04), female (OR 1.58, 95 % CI 1.44-1.73) were the risk factors for long COVID prevalence.

CONCLUSION: Current systematic review found that nearly half of COVID-19 patients may suffering from long COVID in China. Establishing a long COVID recovery-support platform and regular follow-up would help to long-term monitor and manage the patients, especially those high-risk population.}, } @article {pmid39823918, year = {2025}, author = {Wu, D and Manhas, A and Noishiki, C and Tripathi, D and Liu, L and Turbes, N and Thomas, D and Sallam, K and Lee, JT and Sayed, N}, title = {Generation of induced pluripotent stem cell line from a patient with long COVID.}, journal = {Stem cell research}, volume = {83}, number = {}, pages = {103652}, doi = {10.1016/j.scr.2025.103652}, pmid = {39823918}, issn = {1876-7753}, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection, leads to vascular dysfunction, which contributes to the chronic multi-organ damage often seen in affected patients. Long COVID, a global health concern is associated with increased thrombotic risk, also known as COVID-19-associated coagulopathy (CAC). Here, we derived an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a long COVID patient. This iPSC line showed normal morphology, maintained pluripotency, had a stable karyotype, and demonstrated the ability to differentiate into the three germ layers (ectoderm, endoderm, and mesoderm). This line provides a valuable tool for modeling long COVID and exploring mechanisms underlying multi-organ dysfunction.}, } @article {pmid39821993, year = {2025}, author = {Metzmacher, M}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {1}, pages = {32-33}, doi = {10.1007/s15006-024-4450-x}, pmid = {39821993}, issn = {1613-3560}, } @article {pmid39821741, year = {2025}, author = {Jebrini, T and Ruzicka, M and Völk, F and Fonseca, GJI and Pernpruner, A and Benesch, C and Valdinoci, E and von Baum, M and Weigl, M and Subklewe, M and von Bergwelt-Baildon, M and Roider, J and Mayerle, J and Heindl, B and Adorjan, K and Stubbe, HC}, title = {Predicting work ability impairment in post COVID-19 patients: a machine learning model based on clinical parameters.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {39821741}, issn = {1439-0973}, abstract = {The Post COVID-19 condition (PCC) is a complex disease affecting health and everyday functioning. This is well reflected by a patient's inability to work (ITW). In this study, we aimed to investigate factors associated with ITW (1) and to design a machine learning-based model for predicting ITW (2) twelve months after baseline. We selected patients from the post COVID care study (PCC-study) with data on their ability to work. To identify factors associated with ITW, we compared PCC patients with and without ITW. For constructing a predictive model, we selected nine clinical parameters: hospitalization during the acute SARS-CoV-2 infection, WHO severity of acute infection, presence of somatic comorbidities, presence of psychiatric comorbidities, age, height, weight, Karnofsky index, and symptoms. The model was trained to predict ITW twelve months after baseline using TensorFlow Decision Forests. Its performance was investigated using cross-validation and an independent testing dataset. In total, 259 PCC patients were included in this analysis. We observed that ITW was associated with dyslipidemia, worse patient reported outcomes (FSS, WHOQOL-BREF, PHQ-9), a higher rate of preexisting psychiatric conditions, and a more extensive medical work-up. The predictive model exhibited a mean AUC of 0.83 (95% CI: 0.78; 0.88) in the 10-fold cross-validation. In the testing dataset, the AUC was 0.76 (95% CI: 0.58; 0.93). In conclusion, we identified several factors associated with ITW. The predictive model performed very well. It could guide management decisions and help setting mid- to long-term treatment goals by aiding the identification of patients at risk of extended ITW.}, } @article {pmid39820838, year = {2025}, author = {Boscolo-Rizzo, P and Zandonella Callegher, R and Cancellieri, E and Pellegrini, L and Tirelli, G and Albert, U}, title = {Association between psychophysically measured olfactory dysfunction and mental health status in long COVID patients.}, journal = {Rhinology}, volume = {}, number = {}, pages = {}, doi = {10.4193/Rhin24.295}, pmid = {39820838}, issn = {0300-0729}, abstract = {BACKGROUND: Long COVID frequently presents with persistent olfactory dysfunction (OD), affecting both physical and psychological well-being. This study aims to evaluate the mental health consequences of OD in long COVID patients.

METHODOLOGY: A cross-sectional study involved 86 adult patients. Participants presented OD for at least three months post-COVID- 19 and were evaluated using the extended battery of Sniffin' Sticks test (SST). Psychological assessments included the Impact of Event Scale-Revised (IES-R), Beck Hopelessness Scale (BHS), Depression, Anxiety, and Stress Scale-21 (DASS-21), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

RESULTS: Significant differences in mental health factors were observed between patients with and without OD: in comparison to normosmic patients, hyposmic patients showed higher IES-R Total, Avoidance, and Hyperarousal scores, along with increased DASS-21 Anxiety scores and BHS total scores.

CONCLUSIONS: OD in long COVID patients were significantly associated with increased post-traumatic stress symptoms, anxiety symptoms and hopelessness, and with lower quality of life. Limited sample size, inability to determine causation and exploratory nature of the study may limit the generalizability of results. Comprehensive management addressing both physical and mental health should be assessed in long COVID patients.}, } @article {pmid39820631, year = {2025}, author = {Minassie, BB and Degu, WA and Etissa, EK and Asfeha, NF and Alemayehu, ST and Huluka, DK}, title = {Attributes and factors associated with long covid in patients hospitalized for acute COVID-19: A retrospective cohort study.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0317512}, doi = {10.1371/journal.pone.0317512}, pmid = {39820631}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Hospitalization ; Adult ; *SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; Aged ; Risk Factors ; }, abstract = {BACKGROUND: It is now recognized that many patients have persistent symptoms after recovery from acute COVID-19 infection, an infection caused by the coronavirus SARS-CoV-2. This constellation of symptoms known as 'Long COVID' may manifest with a wide range of physical and cognitive/psychological symptoms. Few data are available on the prevalence, attributes, and factors associated with Long COVID in Africa.

METHOD: This was a retrospective review of patients' electronic medical records from Hallelujah General Hospital (one of the first private hospitals to treat COVID-19 patients). The hospital's database was searched for patients hospitalized for acute COVID-19 infection from March 2020 to December 2022. Two hundred and forty-seven participants who underwent follow-up beginning four weeks after symptom onset were assessed for Long COVID. Admission and follow-up data were collected using Kobo Toolbox and exported into SPSS 27 for analysis. The relationship between the independent and dependent variables was explored through binary logistic regression.

RESULTS: One hundred seventy-eight (72.1%) participants had at least one persisting symptom 4 weeks post-symptom onset, at a median follow-up time of 35 (IQR 32-40) days. The most frequently reported symptoms were fatigue (41.7%), shortness of breath (31.2%), cough (27.1%), and sleep disturbances (15%). Duration of symptoms more than 7 days before admission [aOR = 1.97; CI95% = 1.04 to 3.75; P = 0.038] and length of stay more than 10 days in the hospital [aOR = 2.62; CI95% = 1.20 to 5.72; P = 0.016] were found to be significantly associated with Long COVID.

CONCLUSION: There is a high prevalence of Long COVID among patients hospitalized for acute COVID-19. Those who had a longer duration of symptoms before admission and a longer stay in the hospital appear to have a higher risk.}, } @article {pmid39820198, year = {2025}, author = {Anderer, S}, title = {Cognitive Behavioral Therapy Approach May Improve Long COVID Symptoms, Boost Physical Function.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2024.27437}, pmid = {39820198}, issn = {1538-3598}, } @article {pmid39820003, year = {2025}, author = {Andrade, A and Bastos, ACRF and D'Oliveira, A and Vilarino, GT}, title = {Association between physical activity practice and sleep quality of older people in social isolation during the COVID-19 pandemic and Health Guidelines and future studies for the post-COVID period: a systematic review.}, journal = {Aging}, volume = {null}, number = {}, pages = {}, doi = {10.18632/aging.206180}, pmid = {39820003}, issn = {1945-4589}, abstract = {PURPOSE: Physical activity (PA) is considered an alternative to mitigate the negative impacts of the COVID-19 pandemic on the sleep of older adults. The objective was to verify the association between physical activity and the sleep quality of older people in social isolation during the COVID-19 pandemic, to analyze the Health Guidelines, and suggest future studies for the post-COVID period.

METHODS: This systematic review followed PRISMA recommendations, and the protocol was registered in PROSPERO (CRD 42023406471). The search for articles occurred in April 2024 in the databases PubMed, Web of Science, SCOPUS, and gray literature. Data were extracted and checked in a Microsoft Excel[®] spreadsheet. The quality assessment was performed using tools from the National Institutes of Health.

RESULTS: In total, 1582 studies were found in the databases, of which nine were included in the analyses. Four studies reported a negative association of reduced levels of PA during the pandemic with sleep quality, while one study showed a positive association of PA with sleep quality. Four studies demonstrated no association.

CONCLUSIONS: PA was associated with the sleep quality of older adults during the COVID-19 pandemic and reduced levels of PA during this period demonstrated a negative association with sleep quality. Practice of PA is recommended for this post-COVID scenario, as a measure to reduce social isolation and its negative effects and improve the quality of sleep in older adults.}, } @article {pmid39819953, year = {2025}, author = {Sculthorpe, NF and McLaughlin, M and Cerexhe, L and Macdonald, E and Dello Iacono, A and Sanal-Hayes, NEM and Ingram, J and Meach, R and Carless, D and Ormerod, J and Hayes, LD}, title = {Tracking Persistent Symptoms in Scotland (TraPSS): a longitudinal prospective cohort study of COVID-19 recovery after mild acute infection.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e086646}, doi = {10.1136/bmjopen-2024-086646}, pmid = {39819953}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Scotland/epidemiology ; Male ; Female ; Prospective Studies ; Middle Aged ; Longitudinal Studies ; Adult ; *SARS-CoV-2 ; Fatigue/etiology/epidemiology ; Aged ; Post-Acute COVID-19 Syndrome ; Cough/etiology ; Sex Factors ; Age Factors ; }, abstract = {BACKGROUND: COVID-19 disease results in disparate responses between individuals and has led to the emergence of long coronavirus disease (Long-COVID), characterised by persistent and cyclical symptomology. To understand the complexity of Long-COVID, the importance of symptom surveillance and prospective longitudinal studies is evident.

METHODS: A 9-month longitudinal prospective cohort study was conducted within Scotland (n=287), using a mobile app to determine the proportion of recovered individuals and those with persistent symptoms and common symptoms, and associations with gender and age.

RESULTS: 3.1% of participants experienced symptoms at month 9, meeting the criteria for Long-COVID, as defined by the National Institute for Health and Care Excellence terminology. The random effects model revealed a significant time (month) effect for infection recovery (p<0.001, estimate=0.07). Fatigue, cough and muscle pain were the most common symptoms at baseline, with fatigue persisting the longest, while symptoms like cough improved rapidly. Older age increased the likelihood of reporting pain (p=0.028, estimate=0.07) and cognitive impairment (p<0.001, estimate=0.93). Female gender increased the likelihood of headaches (p=0.024, estimate=0.53) and post-exertional malaise (PEM) frequency (p=0.05, estimate=137.68), and increased time x gender effect for PEM frequency (p=0.033, estimate=18.96).

CONCLUSIONS: The majority of people fully recover from acute COVID-19, although often slowly. Age and gender play a role in symptom burden and recovery rates, emphasising the need for tailored approaches to Long-COVID management. Further analysis is required to determine the characteristics of the individuals still reporting ongoing symptoms months after initial infection to identify risk factors and potential predictors for the development of Long-COVID.}, } @article {pmid39818331, year = {2025}, author = {Mohammadi, M and Faghihi, SH}, title = {Drug-resistant tuberculosis is an important challenge in long COVID patients.}, journal = {Journal of global antimicrobial resistance}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgar.2024.12.027}, pmid = {39818331}, issn = {2213-7173}, } @article {pmid39817917, year = {2025}, author = {Bachelet, VC and Carroza, B and Morgado, B and Silva-Ayarza, I}, title = {A systematic analysis of the literature on the post-COVID-19 condition in Latin America focusing on epidemiology, clinical characteristics, and risk of bias.}, journal = {Medwave}, volume = {25}, number = {1}, pages = {e3014}, doi = {10.5867/medwave.2025.01.3014}, pmid = {39817917}, issn = {0717-6384}, mesh = {Humans ; *COVID-19/epidemiology ; Latin America/epidemiology ; *Bias ; Caribbean Region/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Intensive Care Units/statistics & numerical data ; }, abstract = {This analysis article aimed to identify and analyze all articles published on the post-COVID-19 condition in Latin America and the Caribbean, focusing on epidemiology, clinical characteristics, and risk of bias. We did a systematic survey of the literature with broad inclusion criteria. The only exclusion criteria were articles referring to post-acute COVID-19 sequelae after an intensive care unit stay, which we distinguish from the post-COVID-19 condition. We searched MEDLINE/PubMed, LILACS, SciELO, Scopus, Web of Science, and Epistemonikos. We included 55 records, of which 48 were original articles (44 were observational research, 29 of which had a comparison group; and four reviews). Various definitions for long COVID were reported, or none, and few used the World Health Organization criteria. None of the included studies reported prevalence rates for the region. We extracted the reported signs and symptoms of long COVID for our region. Using the Johanna Briggs Institute critical appraisal tools for observational analytic research, we found that most included studies were prone to limitations and biases. We conclude that more research should be done on the post-COVID-19 condition in Latin America and the Caribbean, using rigorous study designs to inform public health strategies.}, } @article {pmid39817308, year = {2025}, author = {Calabrese, LH and Putman, M and Sparks, JA and Wallace, Z and Kim, AHJ and Winthrop, KL and Calabrese, C}, title = {The National Academies' 2024 Diagnostic Criteria for Long COVID: Concerns that Could Affect the Rheumatology Community.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.43114}, pmid = {39817308}, issn = {2326-5205}, } @article {pmid39815057, year = {2025}, author = {Diez-Cirarda, M and Yus-Fuertes, M and Delgado-Alonso, C and Gil-Martínez, L and Jiménez-García, C and Gil-Moreno, MJ and Gómez-Ruiz, N and Oliver-Mas, S and Polidura, C and Jorquera, M and Gómez-Pinedo, U and Arrazola, J and Sánchez-Ramón, S and Matias-Guiu, J and Gonzalez-Escamilla, G and Matias-Guiu, JA}, title = {Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39815057}, issn = {1476-5578}, abstract = {Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered. In this sense, the choroid plexus (ChP) volume has been proposed as a marker of neuroinflammation in immune-mediated conditions and the ChP epithelium has been found particularly susceptible to the effects of SARS-CoV-2. The objective was to investigate the ChP in PCC and evaluate its relationships with cognition, brain, and immunological alterations. One-hundred and twenty-nine patients with PCC after a mean of 14.79 ± 7.17 months of evolution since the infection and 36 healthy controls were recruited. Participants underwent a neuropsychological, and neuroimaging assessment and immunological markers evaluation. Results revealed ChP volume enlargement in PCC compared to healthy controls. The ChP enlargement was associated with cognitive dysfunction, grey matter volume reduction in frontal and subcortical areas, white matter integrity and diffusivity changes and functional connectivity changes. These ChP changes were also related to intermediate monocytes levels. Findings suggest that the ChP integrity may play a relevant role in the pathophysiology of cognitive deficits and the observed brain changes in PCC. The previously documented function of the ChP in maintaining brain homeostasis and regulating the entry of immune cells into the brain supports the presence of neuroinflammatory mechanisms in this disorder.}, } @article {pmid39814621, year = {2025}, author = {Martins, RHG and de Azevedo, ES and Müller, JVC and Loli, A}, title = {Dysphonia and COVID-19: A Review.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2024.11.034}, pmid = {39814621}, issn = {1873-4588}, abstract = {INTRODUCTION: Vocal symptoms are frequent in patients with coronavirus disease 2019 (COVID-19) and may occur during or after infection.

OBJECTIVE: To conduct a descriptive review on the topic "dysphonia and COVID-19" in order to alert specialists to these symptoms associated with the virus and sequelae.

METHODOLOGY: A literature review was carried out in the main databases: Web of Science, PubMed, Google Scholar, and Scopus, between April 2020 and April 2024 using descriptors that related COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) to voice disorders.

RESULTS: In total, 41 studies, 13 case reports, 6 retrospective, and 22 prospective, 5139 patients (2131 M, 2991 F), mean age of 51 years. The prevalence of dysphonia ranged from 0.39% to 79%. The most prevalent vocal symptoms were hoarseness, cough, dry throat, sore throat, reflux, aphonia, phonasthenia, stridor, and hypersecretion. Videolaryngoscopic findings: unilateral paralysis (145), bilateral paralysis (16), erythema (84), benign lesions (56), muscle tension dysphonia (54), granulomas (33), edema (31), stenosis (22), atrophy (19), incomplete glottal closure (12), and ventricular hypertrophy (6). Auditory-perceptual analyses identified mild/moderate vocal impairment in infected patients and persistence of changes in the long-COVID period. Acoustic analyses indicated significant changes in Jitter, Shimmer, harmonic-to-noise ratio (NHR), and maximum phonation time in patients with COVID-19.

CONCLUSION: Dysphonia caused by COVID-19 infection is common, both in the acute and chronic phases of the disease. The main causes include vocal fold paralysis, inflammatory laryngitis, and muscle tension dysphonia. All patients who present vocal symptoms after COVID-19 infection should undergo videolaryngoscopy and subjective and acoustic vocal analyses to identify sequelae of the disease.}, } @article {pmid39812499, year = {2024}, author = {Bętkowska-Korpała, B and Olszewska-Turek, K and Pastuszak-Draxler, A and Laskowska-Wronarowicz, A and Walczewska, J and Starowicz-Filip, A and Dudek, D}, title = {Co-occurrence of psychopathological symptom severity and personality predisposition in post-traumatic stress disorder in patients several months after hospitalisation due to COVID-19.}, journal = {Psychiatria polska}, volume = {}, number = {}, pages = {1-19}, doi = {10.12740/PP/OnlineFirst/183127}, pmid = {39812499}, issn = {2391-5854}, abstract = {OBJECTIVES: The study's aim was to determine co-occurrence of psychopathological symptoms and personality predispositions in post-traumatic stress disorder (PTSD) and its dimensions several months after hospitalisation of patients with severe COVID-19 during the 2nd and 3rd waves of the epidemic.

METHODS: At 7-8 months after admission, 138 patients completed the PCL-5 and TIPI questionnaires, as well as the HADS and AIS scales. Correlation analysis and stepwise multiple regression analysis were used in the models.

RESULTS: 22.5% of patients met the PTSD criteria. There were no significant differences between women and men in terms of severity of anxiety, depression, sleep disorders, distress and PTSD. Anxiety, sleep disorders and depression co-occurred with PTSD severity. All dimensions of PTSD were associated with anxiety. Intrusion, changes in arousal and reactivity correlated with sleep disorders. Changes in arousal and reactivity were explained by subjective assessment of distress. Negative changes in cognition and mood were related to depression and low levels of extraversion.

CONCLUSIONS: There is a co-occurrence of the severity of psychopathological symptoms: anxiety, depression, distress and sleep disorders with the severity of PTDS and its dimensions among patients who have undergone severe COVID-19 in the recent past. A protective factor against post-hospitalisation PTSD is higher level of extraversion.}, } @article {pmid39812099, year = {2024}, author = {Salai, G and Tekavec-Trkanjec, J and Kovačević, I and Tomasović-Lončarić, Č and Pačić, A and Vergles, M and Ljubičić, Đ and Cvetković-Kučić, D and Lukšić, I and Baršić, B}, title = {Lung long distance: histopathological changes in lung tissue after COVID-19 pneumonia.}, journal = {Croatian medical journal}, volume = {65}, number = {6}, pages = {501-509}, pmid = {39812099}, issn = {1332-8166}, mesh = {Humans ; *COVID-19/pathology/complications ; Male ; Cross-Sectional Studies ; Female ; *Lung/pathology ; Middle Aged ; Biopsy ; Aged ; SARS-CoV-2 ; Adult ; }, abstract = {AIM: To investigate histopathological changes in the lung tissue of long-COVID patients.

METHODS: In this cross-sectional study, transbronchial lung biopsy was performed in long-COVID patients with persisting symptoms and radiological abnormalities. Histopathologic analyses were performed by using hematoxylin-eosin, Martius, Scarlet and Blue, Movat's, thyroid transcription factor 1, CD34, and CD68 staining.

RESULTS: Adequate biopsy samples were obtained from 29/32 patients. The median (Q1-Q3) time from disease onset to biopsy was 13 (9-20) weeks. We observed several histopathologic patterns: DAD with vascular abnormalities (VA) (n=8); VA with inflammatory pattern (n=4); inflammatory pattern (n=13), and fibrotic pattern (n=4). VA included capillary thrombi, dilated venules, and dissection of small pulmonary arteries. DAD with VA was detected up to the 9th week from the onset of disease; inflammatory pattern from the 8th to 28th week (4 patients with this pattern biopsied in the 11th-13th week had accompanying VA); and a predominantly fibrotic pattern was found at weeks 8, 10, 48, and 49.

CONCLUSION: Our study observed a slow recovery of lung tissue with long-lasting DAD and VA, likely followed by interstitial inflammation or focal fibrosis. These findings might be the underlying cause of the slow recovery of long-COVID patients.}, } @article {pmid39811236, year = {2024}, author = {Razzak, AN and Kaizu, Y and Starkey, J}, title = {A Comparative Review of the Terms Epipharyngitis and Nasopharyngitis in Medical Literature.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75738}, pmid = {39811236}, issn = {2168-8184}, abstract = {This review explores the usage of the term "epipharyngitis" in medical literature, particularly in non-English-speaking contexts. The term, although rarely used in contemporary English-language medical literature, may lead to confusion due to its overlap with more commonly used terms like "nasopharyngitis." This review aims to trace the origins of the term, analyze its usage across different languages, and discuss the implications of term differences in clinical practice and medical education.}, } @article {pmid39810272, year = {2025}, author = {Tsuruoka, M and Huynh, MK and Toizumi, M and Hoang, TT and Nguyen, TB and Dao, AT and Nguyen, LD and Le, HX and Le, CT and Dang, AQ and Do, HT and Yoshida, LM}, title = {Characteristics and long-term health outcomes of the first domestic COVID-19 outbreak cases in Da Nang, Vietnam: a longitudinal cohort study.}, journal = {Tropical medicine and health}, volume = {53}, number = {1}, pages = {6}, pmid = {39810272}, issn = {1348-8945}, support = {JP21wm0125006//Japan Program for Infectious Diseases Research and Infrastructure, Japan Agency for Medical Research and Development (AMED)/ ; 27-Ippan-17//Joint Usage / Research Centre on Tropical Disease, Institute of Tropical Medicine, Nagasaki University/ ; }, abstract = {BACKGROUND: Vietnam experienced the first COVID-19 domestic outbreak due to the Wuhan strain (B.1.1) in Da Nang from July 2020. COVID-19 can cause acute as well as long-term health problems. We aimed to characterise clinical features and risk factors related to severe illness of COVID-19 among Da Nang outbreak cases and to describe long-term health outcomes among survivors of this outbreak.

METHODS: We conducted an ambidirectional cohort study. Study subjects were all hospitalised cases with positive real-time PCR test of SARS-CoV-2 in the three major hospitals in Da Nang from 25 July to 28 August 2020. Clinical and demographic information was retrospectively collected from medical charts. Then, the survivors were followed-up prospectively at 6 and 16 months after acute infection to assess their health status via standardized questionnaires, physical examinations, chest X-rays and pulmonary function tests.

RESULTS: A total of 362 cases including 20 fatal cases were enrolled into the study retrospectively. The median age of the participants included in the medical chart review was 46.5 years and 60.8% were female. Overall, 7.8% of the participants required respiratory support during hospitalisation and 20 of them died. Compared to the survivors, the fatal cases were significantly older (median age of survivors 45.0 yr vs fatal cases 66.5 yr, P < 0.001) and more likely to have underlying conditions. The proportions of participants who had at least one long COVID symptom within the 7 days of each follow-up at 6 and 16 months were 72.0% (134/186) and 63.5% (47/74), respectively. We also found that females and adults reported symptoms more often in the follow-up surveys, 78.9% (90/114) [females] vs 61.1% (44/72) [males] at 6 months, P = 0.008; 68.7% (46/67) [ ≥ 20 years] vs 14.3% (1/7) [ < 20 years] at 16 months, P = 0.004.

CONCLUSIONS: In the first domestic COVID-19 outbreak in Vietnam, the mortality rate was approximately 6% and associated with underlying medical conditions. In the follow-up surveys, a substantial proportion of participants reported long COVID related health problems, although the prevalence declined over time. Females and adults reported symptoms more often, which might be due to the pathophysiological differences according to sex and age.}, } @article {pmid39809593, year = {2025}, author = {Drover, H and Singh, SJ and Orme, MW and Daynes, E}, title = {Pulmonary rehabilitation healthcare professionals understanding and experiences of the protected characteristics of service users: A qualitative analysis.}, journal = {Chronic respiratory disease}, volume = {22}, number = {}, pages = {14799731241307253}, doi = {10.1177/14799731241307253}, pmid = {39809593}, issn = {1479-9731}, mesh = {Humans ; Female ; Male ; *Qualitative Research ; Adult ; *Attitude of Health Personnel ; Middle Aged ; Health Personnel/psychology ; Health Services Accessibility ; Healthcare Disparities ; Interviews as Topic ; Age Factors ; Physical Therapists ; Gender Identity ; Pregnancy ; Occupational Therapists/psychology ; }, abstract = {BACKGROUND: Health inequalities can affect access and uptake to pulmonary rehabilitation (PR). An individual's protected characteristics (age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion or belief, sex and sexual orientation) may contribute to health inequalities. Healthcare professionals (HCPs) experiences of the inclusivity and representativeness of PR services and knowledge of protected characteristics are unknown, however are vital for the identification and resolution of health inequalities. This qualitative study explored HCPs understanding of protected characteristics and their perception of the inclusivity, representativeness and equitable benefit of their PR services.

METHODS: Semi-structured qualitative interviews were conducted in person or via videoconferencing with HCPs involved in PR from two healthcare providers. Interviews were analysed using reflexive thematic analysis.

RESULTS: 12 interviews were conducted with physiotherapists (n = 6), occupational therapists (n = 2), nurses (n = 2) and exercise physiologists (n = 2). Participants had a median (IRQ) age of 43 (13) and 75% (n = 9) were female. Four themes were generated. 1: 'I don't really know as much as I should' [about protected characteristics]; 2: It's uncomfortable collecting protected characteristics…; 3: 'I don't think [service users] are as representative as they could be'; 4: A conventional rehabilitation programme does not meet the needs of all.

CONCLUSIONS: This study highlighted several challenges in HCPs understanding of protected characteristics and the representativeness of PR that must be addressed to ensure equity. Strategies, to understand barriers in accessing PR that limit representativeness should be explored.}, } @article {pmid39808169, year = {2024}, author = {Šerý, O and Dziedzinska, R}, title = {Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.}, journal = {Physiological research}, volume = {73}, number = {S3}, pages = {S655-S669}, pmid = {39808169}, issn = {1802-9973}, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/metabolism ; *SARS-CoV-2/pathogenicity ; *Angiotensin-Converting Enzyme 2/metabolism ; Animals ; Myocytes, Cardiac/metabolism/virology/pathology ; Virus Internalization ; Myocardium/metabolism/pathology ; }, abstract = {The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.}, } @article {pmid39806627, year = {2024}, author = {Baalmann, AK and Blome, C and Stoletzki, N and Donhauser, T and Apfelbacher, C and Piontek, K}, title = {Patient-reported outcome measures for post-COVID-19 condition: a systematic review of instruments and measurement properties.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e084202}, doi = {10.1136/bmjopen-2024-084202}, pmid = {39806627}, issn = {2044-6055}, mesh = {Humans ; *Patient Reported Outcome Measures ; *COVID-19 ; *Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Post-COVID-19 condition (PCC), also referred to as Long COVID, has become an emerging public health issue requiring adequate prevention, treatment and management strategies. Evaluating these strategies from the patients' perspective using patient-reported outcome measures (PROMs) is critical. In this systematic review, we aimed to critically appraise and summarise the quality of existing PROMs for PCC, and to identify PROMs that can be recommended for use in future research.

DESIGN: Systematic review using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology.

DATA SOURCES: PubMed and Web of Science were searched on 16 January 2023 and again on 23 July 2024.

ELIGIBILITY CRITERIA: We included studies reporting on the development and/or validation of any disease-specific PROMs for PCC.

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the results for eligibility. The methodological quality of each included study was assessed using the COSMIN Risk of Bias Checklist. We further evaluated the quality of measurement properties per PROM and study according to the criteria for good measurement properties as outlined in the COSMIN manual, and graded the evidence of the synthesised results. Based on the overall evidence, we derived recommendations for the use of the identified instruments.

RESULTS: We identified 23 studies reporting on 11 PROMs measuring functional status (COVID-19 Yorkshire Rehabilitation Scale, C19-YRS; Modified COVID-19 Yorkshire Rehabilitation Scale, C19-YRSm; Functional Impairment Checklist, FIC; Post-COVID-19 Functional Status Scale, PCFS), symptom burden and impact (Long COVID Symptom and Severity Score, LC-SSS; Long COVID Symptom Tool, LCST; Long COVID Impact Tool, LCIT; Symptom Burden Questionnaire Long COVID, SBQ-LC), quality of life (Post-acute COVID-19 Quality of Life instrument, PAC-19QoL) and stigma (Long COVID Stigma Scale, LCSS; Post-COVID-19 Condition Stigma Questionnaire, PCCSQ). Sample sizes of the included studies ranged from 29 to 1969 participants. Overall, 95 single studies on measurement properties were evaluated. Among the identified instruments, the Long Covid Stigma Scale (LCSS) showed sufficient content validity and internal consistency and can be recommended for use according to COSMIN criteria. Our assessment of measurement properties revealed significant evidence gaps for all PROMs, indicating the need for further validation studies to make an adequate decision on the recommendation for their use. Content validity is a major shortcoming of all included instruments.

CONCLUSION: The LCSS measuring stigma can be recommended for use in future research. For the assessment of PCC symptoms and impact, no instrument with sufficient measurement properties is currently available. Further validation of all identified PROMs is indicated, in particular comprehensive assessments of content validity involving experts and patients.

PROSPERO REGISTRATION NUMBER: CRD42023391238.}, } @article {pmid39804864, year = {2025}, author = {Thapaliya, K and Marshall-Gradisnik, S and Eaton-Fitch, N and Barth, M and Inderyas, M and Barnden, L}, title = {Hippocampal subfield volume alterations and associations with severity measures in long COVID and ME/CFS: A 7T MRI study.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0316625}, doi = {10.1371/journal.pone.0316625}, pmid = {39804864}, issn = {1932-6203}, mesh = {Humans ; *Hippocampus/diagnostic imaging/pathology ; *Magnetic Resonance Imaging/methods ; Female ; Male ; *COVID-19/diagnostic imaging/pathology/complications ; Middle Aged ; Adult ; *Fatigue Syndrome, Chronic/diagnostic imaging/pathology ; SARS-CoV-2 ; Severity of Illness Index ; Case-Control Studies ; Organ Size ; }, abstract = {Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients share similar symptoms including post-exertional malaise, neurocognitive impairment, and memory loss. The neurocognitive impairment in both conditions might be linked to alterations in the hippocampal subfields. Therefore, this study compared alterations in hippocampal subfields of 17 long COVID, 29 ME/CFS patients, and 15 healthy controls (HC). Structural MRI data was acquired with sub-millimeter isotropic resolution on a 7 Telsa MRI scanner and hippocampal subfield volumes were then estimated for each participant using FreeSurfer software. Our study found significantly larger volumes in the left hippocampal subfields of both long COVID and ME/CFS patients compared to HC. These included the left subiculum head (long COVID; p = 0.01, ME/CFS; p = 0.002,), presubiculum head (long COVID; p = 0.004, ME/CFS; p = 0.005), molecular layer hippocampus head (long COVID; p = 0.014, ME/CFS; p = 0.011), and whole hippocampal head (long COVID; p = 0.01, ME/CFS; p = 0.01). Notably, hippocampal subfield volumes were similar between long COVID and ME/CFS patients. Additionally, we found significant associations between hippocampal subfield volumes and severity measures of 'Pain', 'Duration of illness', 'Severity of fatigue', 'Impaired concentration', 'Unrefreshing sleep', and 'Physical function' in both conditions. These findings suggest that hippocampal alterations may contribute to the neurocognitive impairment experienced by long COVID and ME/CFS patients. Furthermore, our study highlights similarities between these two conditions.}, } @article {pmid39804551, year = {2025}, author = {Vernon, SD and Zheng, T and Do, H and Marconi, VC and Jason, LA and Singer, NG and Natelson, BH and Sherif, ZA and Bonilla, HF and Taylor, E and Mullington, JM and Ashktorab, H and Laiyemo, AO and Brim, H and Patterson, TF and Akintonwa, TT and Sekar, A and Peluso, MJ and Maniar, N and Bateman, L and Horwitz, LI and Hess, R and , }, title = {Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {39804551}, issn = {1525-1497}, support = {OTA OT2HL161841/HL/NHLBI NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; OT2HL156812/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may occur after infection. How often people develop ME/CFS after SARS-CoV-2 infection is unknown.

OBJECTIVE: To determine the incidence and prevalence of post-COVID-19 ME/CFS among adults enrolled in the Researching COVID to Enhance Recovery (RECOVER-Adult) study.

RECOVER-Adult is a longitudinal observational cohort study conducted across the U.S. We included participants who had a study visit at least 6 months after infection and had no pre-existing ME/CFS, grouped as (1) acute infected, enrolled within 30 days of infection or enrolled as uninfected who became infected (n=4515); (2) post-acute infected, enrolled greater than 30 days after infection (n=7270); and (3) uninfected (1439).

MEASUREMENTS: Incidence rate and prevalence of post-COVID-19 ME/CFS based on the 2015 Institute of Medicine ME/CFS clinical diagnostic criteria.

RESULTS: The incidence rate of ME/CFS in participants followed from time of SARS-CoV-2 infection was 2.66 (95% CI 2.63-2.70) per 100 person-years while the rate in matched uninfected participants was 0.93 (95% CI 0.91-10.95) per 100 person-years: a hazard ratio of 4.93 (95% CI 3.62-6.71). The proportion of all RECOVER-Adult participants that met criteria for ME/CFS following SARS-CoV-2 infection was 4.5% (531 of 11,785) compared to 0.6% (9 of 1439) in uninfected participants. Post-exertional malaise was the most common ME/CFS symptom in infected participants (24.0%, 2830 of 11,785). Most participants with post-COVID-19 ME/CFS also met RECOVER criteria for long COVID (88.7%, 471 of 531).

LIMITATIONS: The ME/CFS clinical diagnostic criteria uses self-reported symptoms. Symptoms can wax and wane.

CONCLUSION: ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection. RECOVER provides an unprecedented opportunity to study post-COVID-19 ME/CFS.}, } @article {pmid39802657, year = {2024}, author = {Wei, Y and Gu, H and Ma, J and Mao, X and Wang, B and Wu, W and Yu, S and Wang, J and Zhao, H and He, Y}, title = {Proteomic and metabolomic profiling of plasma uncovers immune responses in patients with Long COVID-19.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1470193}, pmid = {39802657}, issn = {1664-302X}, abstract = {Long COVID is an often-debilitating condition with severe, multisystem symptoms that can persist for weeks or months and increase the risk of various diseases. Currently, there is a lack of diagnostic tools for Long COVID in clinical practice. Therefore, this study utilizes plasma proteomics and metabolomics technologies to understand the molecular profile and pathophysiological mechanisms of Long COVID, providing clinical evidence for the development of potential biomarkers. This study included three age- and gender-matched cohorts: healthy controls (n = 18), COVID-19 recovered patients (n = 17), and Long COVID patients (n = 15). The proteomics results revealed significant differences in proteins between Long COVID-19 patients and COVID-19 recovered patients, with dysregulation mainly focused on pathways such as coagulation, platelets, complement cascade reactions, GPCR cell signal transduction, and substance transport, which can participate in regulating immune responses, inflammation, and tissue vascular repair. Metabolomics results showed that Long COVID patients and COVID-19 recovered patients have similar metabolic disorders, mainly involving dysregulation in lipid metabolites and fatty acid metabolism, such as glycerophospholipids, sphingolipid metabolism, and arachidonic acid metabolism processes. In summary, our study results indicate significant protein dysregulation and metabolic abnormalities in the plasma of Long COVID patients, leading to coagulation dysfunction, impaired energy metabolism, and chronic immune dysregulation, which are more pronounced than in COVID-19 recovered patients.}, } @article {pmid39802304, year = {2025}, author = {Pouliopoulou, DV and Billias, N and MacDermid, JC and Miller, E and O'Brien, KK and Quinn, KL and Malvankar-Mehta, MS and Pereira, TV and Cheung, AM and Razak, F and Stranges, S and Bobos, P}, title = {Prevalence of post-acute sequelae of SARS-CoV-2 infection in people living with HIV: a systematic review with meta-analysis.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {102993}, pmid = {39802304}, issn = {2589-5370}, abstract = {BACKGROUND: Given the chronic immune activation and inflammatory milieu associated with Long COVID and HIV, we assessed the prevalence of Long COVID in adults living with HIV; and investigated whether adults living with HIV were associated with increased chance of developing Long COVID compared to adults living without HIV.

METHODS: In this systematic review and meta-analysis, we searched Medline, EMBASE, CINHAL, PubMed and CENTRAL from inception until June 14th, 2024, for observational studies that measured the prevalence of Long COVID in adults living with HIV and the odds of developing Long COVID following a SARS-CoV-2 infection in people living with HIV compared to people living without HIV. Reviews, case reports, randomised control trials and editorials were excluded. The search was conducted without language restrictions. We performed meta-analysis of proportions to synthesise prevalence estimates using logit transformation and a sensitivity analysis using mixed-effects logistic regression. We used random-effects meta-analyses to summarize the odds ratio (OR) of developing Long COVID in adults living with HIV compared to adults living without HIV and conducted a sensitivity analysis including only studies with covariate-adjusted estimates that was planned a-priori. We used ROBINS-E for the risk of bias assessment and GRADE to rate the certainty of evidence. We identified statistical heterogeneity using Cochran's Q test and quantified it using the I[2] statistic. For the Q test, a P < 0.10 was considered statistically significant. PROSPERO registration: CRD42024577616.

FINDINGS: Our search returned 831 results, of which 8 studies (4489 participants) were deemed eligible for inclusion in the systematic review and meta-analysis. The prevalence of Long COVID in adults with HIV was 43% (95% CI: 32-54%, 8 studies; 1227 participants; low certainty, I[2] < 0.0001). The association of HIV status with Long COVID was inconclusive, with wide confidence intervals (OR: 1.16, 95% CI: 0.58-2.29; 4 studies; 3556 participants, low certainty, I[2] = 0.013). When the analysis was restricted to studies reporting covariate-adjusted estimates, adults living with HIV were associated with a higher odds of Long COVID than those not living with HIV (OR: 2.21, 95% CI: 1.12-4.36; 2 studies; 374 participants, low certainty, I[2] = 0.51).

INTERPRETATION: Current evidence indicates that the prevalence of Long COVID in adults living with HIV may be high, suggesting the need for increased awareness and education of healthcare providers and policy makers. Evidence on whether HIV positivity increases the risk of Long COVID is limited and inconclusive, highlighting a need for further research to clarify this potential association.

FUNDING: None.}, } @article {pmid39800813, year = {2025}, author = {Mohd Yusoff, H and Yew, SQ and Mohammed Nawi, A and Htwe, O and Mohd Tohit, N and Mohamed, Z and Muhamad Noordin, MA and Che Mohamed, N and Mohd, FH}, title = {Prevalence and symptoms of Long Covid-19 in the workplace.}, journal = {Occupational medicine (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/occmed/kqae128}, pmid = {39800813}, issn = {1471-8405}, support = {UKMP-S230424//National Institute of Occupational Safety and Health (NIOSH) Malaysia/ ; }, abstract = {BACKGROUND: The symptoms of Long coronavirus disease 2019 (Covid-19) are heterogeneous, creating uncertainty for employers regarding the diagnosis. The prevalence of Long Covid-19 in the workforce is also unknown. Furthermore, workers affected by Long Covid-19 encounter considerable difficulties in ensuring work safety and returning to their jobs due to this condition.

AIMS: This review is aimed to identify the prevalence of Long Covid-19 in the workplace and to determine the various symptoms of Long Covid-19 experienced by the workers.

METHODS: A meta-analysis was conducted to calculate the pooled estimates for the prevalence of Long Covid-19. Heterogeneity among the estimates was evaluated using the I² statistic.

RESULTS: The pooled prevalence of Long Covid-19 among workers across the 11 studies was 38% (95% CI 23-56). A total of 43 symptoms associated with Long Covid-19 were identified in the workplace, with the top five symptoms being dyspnoea at moderate activity (51%, 95% CI 39-62), mental symptoms (38%, 95% CI 6-87), dyspnoea at mild activity (35%, 95% CI 25-47), fatigue (26%, 95% CI 3-78) and effort intolerance (24%, 95% CI 15-35).

CONCLUSIONS: The review indicates a significant burden of long-lasting symptoms within the workforce. The top five reported symptoms of Long Covid-19 were dyspnoea during mild and moderate activities, mental symptoms, fatigue and effort intolerance.}, } @article {pmid39800769, year = {2025}, author = {Alonso Domínguez, J and Martínez Barros, I and Viéitez, I and Peleteiro, M and Calderón-Cruz, B and González-Nóvoa, JA and Pérez González, A and Leiro Fernández, V and López López, A and Poveda López, E}, title = {SARS-CoV-2 Viral Load and Cytokine Dynamics Profile as Early Signatures of Long COVID Condition in Hospitalized Individuals.}, journal = {Influenza and other respiratory viruses}, volume = {19}, number = {1}, pages = {e70068}, doi = {10.1111/irv.70068}, pmid = {39800769}, issn = {1750-2659}, support = {P19/00747//Instituto de Salud Carlos III (ISCIII)/ ; PI22/01341//Instituto de Salud Carlos III (ISCIII)/ ; FI23/00006//Instituto de Salud Carlos III (ISCIII)/ ; }, mesh = {Humans ; *Viral Load ; *COVID-19/virology/blood/diagnosis ; *SARS-CoV-2/isolation & purification/genetics ; *Cytokines/blood ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Adult ; Hospitalization ; RNA, Viral/blood ; Post-Acute COVID-19 Syndrome ; Nasopharynx/virology ; }, abstract = {BACKGROUND: The global pandemic caused by SARS-CoV-2 has resulted in millions of people experiencing long COVID condition, a range of persistent symptoms following the acute phase, with an estimated prevalence of 27%-64%.

MATERIALS AND METHODS: To understand its pathophysiology, we conducted a longitudinal study on viral load and cytokine dynamics in individuals with confirmed SARS-CoV-2 infection. We used reverse transcriptase droplet digital PCR to quantify viral RNA from nasopharyngeal swabs and employed multiplex technology to measure plasma cytokine levels in a cohort of people with SARS-CoV-2 infection. Our study included individuals with long COVID condition and those without, all of whom had at least three nasopharyngeal and plasma samples collected within 55 days after diagnosis of SARS-CoV-2 infection.

RESULTS: Individuals affected with long COVID symptoms had delayed viral clearance and lower viral loads at diagnosis compared to those without symptoms. Additionally, cytokine analysis revealed variations in IL-18, MIG, and IP-10 levels, with delayed normalization in individuals affected by long COVID syndrome. Correlation analysis indicated associations between viral load and IP-10 and interrelations among cytokines IL-1β, IL-18, MIG, and IP-10.

CONCLUSION: Our study provides insights into the association between nasopharyngeal viral load, cytokine dynamics, and the development of long COVID syndrome, providing an early signature of this condition.}, } @article {pmid39799876, year = {2025}, author = {Muzaffar-Ur-Rehman, M and Chougule, KS and Chandu, A and Kuthe, PV and Garg, M and Sankaranarayanan, M and Vasan, SS}, title = {In silico evaluation of bisphosphonates identifies leading candidates for SARS-CoV-2 RdRp inhibition.}, journal = {Journal of molecular graphics & modelling}, volume = {136}, number = {}, pages = {108939}, doi = {10.1016/j.jmgm.2024.108939}, pmid = {39799876}, issn = {1873-4243}, abstract = {The novel coronavirus disease (COVID-19) pandemic has resulted in 777 million confirmed cases and over 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Post Acute Sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. In this study, we have investigated all bisphosphonates (BPs) on the ChEMBL database which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies in Japan with minodronate could be valuable.}, } @article {pmid39799724, year = {2025}, author = {Betancourt-Peña, J and Rodriguez-Castro, J and Perez-Hortua, V and Ávila-Valencia, JC and Benavides-Córdoba, V}, title = {[Post-COVID-19 Functional status scale: Concordance between evaluator-administered versus self-assessed version in patients with post-COVID-19 syndrome].}, journal = {Rehabilitacion}, volume = {59}, number = {1}, pages = {100878}, doi = {10.1016/j.rh.2024.100878}, pmid = {39799724}, issn = {1578-3278}, abstract = {INTRODUCTION: Patients diagnosed with COVID-19 may present sequelae which are called Post COVID-19 Syndrome or Long COVID in which physical, psychological and/or social complications are evident. The objective of this study was to evaluate the agreement of the Post-COVID-19 Functional Status Scale (PCFS) of the evaluator-administered version vs patient self-assessed in post-COVID-19 patients.

METHODS: Observational study in patients diagnosed with COVID-19 with subsequent recovery. Once the project was approved by the ethics committee and the patients signed the informed consent, a survey was carried out to collect sociodemographic and clinical data and the application of the PCFS scale, in its two forms, self-administered and by an evaluator.

RESULTS: 97 patients entered the study, 57.7% being women. The agreement analysis determined a concordance index of 0.857 95% CI (0.7-0.934) (almost perfect agreement). The agreement for women was 0.817 95% CI 0.700-0.934 and for men 0.907 95% CI (0.806-1).

CONCLUSION: The use of the Spanish version of the PCFS scale carried out by the health professional compared to the version self-assessed by patients, demonstrates adequate agreement.}, } @article {pmid39799217, year = {2025}, author = {Charles James, J and Schulze, H and Siems, N and Prehn, C and Quast, DR and Trampe, N and Gold, R and Faissner, S}, title = {Neurological post-COVID syndrome is associated with substantial impairment of verbal short-term and working memory.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1695}, pmid = {39799217}, issn = {2045-2322}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/psychology/complications/epidemiology ; *Neuropsychological Tests ; *Memory, Short-Term ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Cognitive Dysfunction/etiology ; SARS-CoV-2/isolation & purification ; Fatigue/etiology ; }, abstract = {A substantial proportion of patients suffer from Post-COVID Syndrome (PCS) with fatigue and impairment of memory and concentration being the most important symptoms. We here set out to perform in-depth neuropsychological assessment of PCS patients referred to the Neurologic PCS clinic compared to patients without sequelae after COVID-19 (non-PCS) and healthy controls (HC) to decipher the most prevalent cognitive deficits. We included n = 60 PCS patients with neurologic symptoms, n = 15 non-PCS patients and n = 15 healthy controls. Basic socioeconomic data and subjective complaints were recorded. This was followed by a detailed neuropsychological test battery, including assessments of general orientation, motor and cognitive fatigue, screening of depressive and anxiety symptoms, information processing speed, concentration, visuomotor processing speed, attention, verbal short-term and working memory, cognitive flexibility, semantic and phonematic word fluency, as well as verbal and visual memory functions. Neurologic PCS patients had more complaints with significantly higher fatigue scores as well as higher levels of depressive and anxiety symptoms compared to Non-PCS and HC. Deep neuropsychological assessment showed that neurologic PCS patients performed worse in a general screening of cognitive deficits compared to HC. Neurologic PCS patients showed impaired mental flexibility as an executive subfunction, verbal short-term memory, working memory and general reactivity (prolonged reaction time). Multiple regression showed fatigue affected processing speed; depression did not. Self-reported cognitive deficits of patients with neurologic PCS including fatigue, concentration, and memory deficits, are well mirrored in impaired performance of cognitive domains of concentration and working memory. The present results should be considered to optimize treatment algorithms for therapy and rehabilitation programs of PCS patients with neurologic symptoms.}, } @article {pmid39798903, year = {2025}, author = {Park, S and Lee, YW and Choi, S and Jo, H and Kim, N and Cho, S and Lee, E and Choi, EB and Park, I and Jeon, Y and Noh, H and Seok, SH and Oh, SH and Choi, YK and Kwon, HK and Seo, JY and Nam, KT and Park, JW and Choi, KS and Lee, HY and Yun, JW and Seong, JK}, title = {Post-COVID metabolic enzyme alterations in K18-hACE2 mice exacerbate alcohol-induced liver injury through transcriptional regulation.}, journal = {Free radical biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2025.01.015}, pmid = {39798903}, issn = {1873-4596}, abstract = {Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Despite reports of liver injury during viral disease, the occurrence and detailed mechanisms underlying the development of secondary exogenous liver injury, particularly in relation to changes in metabolic enzymes, remain to be fully elucidated. Therefore, this study was aimed to investigate the mechanisms underlying SARS-CoV-2-induced molecular alterations in hepatic metabolism and the consequent secondary liver injury resulting from alcohol exposure. We investigated the potential effects of SARS-CoV-2 infection on alcohol-induced liver injury in Keratin 18 promoter-human angiotensin converting enzyme 2 (K18-hACE2) transgenic mice. Mice were intranasally infected with 1×10[2] PFU of SARS-CoV-2. Following a 14 d recovery period from infection, the recovered mice were orally administered alcohol at 6 g/kg. Prior SARS-CoV-2 infection aggravated alcohol-induced liver injury based on increased alanine aminotransferase levels and cytoplasmic vacuolation. Interestingly, infected mice exhibited lower blood alcohol levels and higher levels of acetaldehyde, a toxic alcohol metabolite, compared to uninfected mice after the same period of alcohol consumption. Along with alterations of several metabolic process-related terms identified through RNA sequencing, notably, upregulation of cytochrome P450 2E1 (CYP2E1) and CYP1A2 was observed in infected mice compared to control value prior to alcohol exposure, with no significant impact of SARS-CoV-2 on intestinal damage. Tumor necrosis factor-alpha persistently showed upregulated expression in the infected mice; it also enhanced aryl hydrocarbon receptor and Sp1 expressions and their binding activity to Cyp1a2 and Cyp2e1 promoters, respectively, in hepatocytes, promoting the upregulation of their transcription. Our findings suggest that SARS-CoV-2 infection exacerbates alcohol-induced liver injury through the transcriptional activation of Cyp1a2 and Cyp2e1, providing valuable insights for the development of clinical recommendations on long COVID.}, } @article {pmid39798220, year = {2025}, author = {Vo, HT and Dao, TV and Do, TX and Do, BN and Nguyen, TT and Pham, KM and Vu, VH and Pham, LV and Nguyen, LTH and Le, LTH and Nguyen, HC and Tran, TV and Nguyen, TH and Nguyen, AT and Nguyen, HV and Nguyen, PB and Pham, TTM and Dao, TD and Le, TT and Nguyen, TTP and Tran, CQ and Nguyen, KT and Duong, TV}, title = {Association between underlying health conditions and long COVID among non-hospitalized and hospitalized individuals as modified by health literacy: A multi-center study.}, journal = {Public health}, volume = {239}, number = {}, pages = {87-93}, doi = {10.1016/j.puhe.2024.12.032}, pmid = {39798220}, issn = {1476-5616}, abstract = {OBJECTIVES: We investigated the effect modification of health literacy (HL) in ameliorating the negative impact of underlying health conditions (UHC) on long COVID among non-hospitalized and hospitalized survivors.

STUDY DESIGN: An online cross-sectional study was conducted in Vietnam from December 2021 to October 2022.

METHODS: A sample of 4507 participants recruited from 18 hospitals and health centers were those aged 18 or older, had contracted COVID-19 for at least 28 days, and were not in the acute phase of reinfection. Participants reported their long COVID symptoms, UHC, health literacy, socio-demographics, clinical parameters, the COVID-19 impact battery disability scale, and health-related behaviors. The logistic regression models were used to examine the associations and interactions.

RESULTS: Underlying health conditions were associated with a higher likelihood of long COVID in non-hospitalized participants (adjusted odds ratio, aOR = 2.10 [1.61, 2.61]; p < 0.001), and hospitalized ones (aOR = 2.26 [1.87, 2.73]; p < 0.001). In non-hospitalized participants, higher HL scores were significantly linked to a reduced likelihood of experiencing long COVID (aOR = 0.96 [0.95, 0.97]; p < 0.001). Furthermore, HL moderated the adverse effect of underlying health conditions (UHC) on long COVID in this group (aOR = 0.97 [0.94-0.99]; p = 0.042). In hospitalized participants, although higher HL scores were also associated with a lower risk of long COVID (aOR = 0.99 [0.98-0.99]; p = 0.036), HL did not significantly mitigate the negative impact of UHC on long COVID (aOR = 1.01 [0.99-1.03]; p = 0.332).

CONCLUSIONS: In non-hospitalized individuals, high health literacy ameliorated the negative impact of UHC on long COVID. Such effects of health literacy were not observed in hospitalized COVID-19 survivors.}, } @article {pmid39797180, year = {2024}, author = {Godfrey, B and Shardha, J and Witton, S and Bodey, R and Tarrant, R and Greenwood, DC and Sivan, M}, title = {A Personalised Pacing and Active Rest Rehabilitation Programme for Post-Exertional Symptom Exacerbation and Health Status in Long COVID (PACELOC): A Prospective Cohort Study.}, journal = {Journal of clinical medicine}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/jcm14010097}, pmid = {39797180}, issn = {2077-0383}, abstract = {Background: Post-COVID-19 Syndrome or long COVID (LC) is a novel public health crisis and, when persistent (>2 years), is a long-term condition. Post-exertional symptom exacerbation (PESE) is a characteristic symptom of LC and can be improved in a structured pacing rehabilitation programme. Aims: To evaluate the effect of an 8-week structured World Health Organisation (WHO) Borg CR-10 pacing protocol on PESE episodes, LC symptoms, and quality of life in a cohort of individuals with long-term LC. Methods: Participants received weekly telephone calls with a clinician to discuss their activity phase, considering their PESE symptoms that week. They completed the Leeds PESE questionnaire (LPQ), C19-YRS (Yorkshire Rehabilitation Scale), and EQ-5D-5L at the beginning of the programme (0 weeks), the end of programme (8 weeks), and at final follow-up (12 weeks). Results: Thirty-one participants (duration of LC symptoms: 29 months) completed the programme. The PESE episodes decreased in number each week (15% fewer each week, 95% CI: 11% to 20%, p < 0.001) and were of shorter duration and milder severity each week. The changes in C19YRS symptom severity and functional disability (0-12 weeks) were statistically significant but not clinically significant. The EQ5D-5L index score change was not statistically significant. Conclusions: A structured pacing protocol effectively reduced PESE episode frequency, duration, and severity but did not produce clinically significant changes in LC symptoms, reflecting the long-term nature of the condition in this cohort.}, } @article {pmid39796218, year = {2025}, author = {Yip, JMX and Chiang, GSH and Lee, ICJ and Lehming-Teo, R and Dai, K and Dongol, L and Wang, LY and Teo, D and Seah, GT and Lehming, N}, title = {Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, doi = {10.3390/ijms26010364}, pmid = {39796218}, issn = {1422-0067}, support = {A-8000724-00-00//Ministry of Education/ ; }, mesh = {Humans ; *Drug Repositioning/methods ; *Mitochondria/metabolism/drug effects ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; Metformin/therapeutic use/pharmacology ; SARS-CoV-2/drug effects ; COVID-19/metabolism/virology ; Off-Label Use ; Diabetes Mellitus/drug therapy/metabolism ; Animals ; }, abstract = {This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.}, } @article {pmid39795908, year = {2024}, author = {Luzak, B and Golanski, J and Rozalski, M}, title = {Complex Pattern of Platelet Activation/Reactivity After SARS-CoV-2 Infection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {1}, pages = {}, doi = {10.3390/ijms26010049}, pmid = {39795908}, issn = {1422-0067}, support = {503/6-020-01/503-61-001//Medical University of Lodz, Poland/ ; }, mesh = {Humans ; *COVID-19/blood/virology/immunology ; *Platelet Activation ; *SARS-CoV-2 ; *Blood Platelets/metabolism ; Platelet Aggregation ; Platelet Function Tests ; }, abstract = {COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology. Elevated levels of soluble markers of platelet activation (P selectin, PF4), increased platelet aggregates, and platelet-derived microparticles suggest the activation of platelets circulating in the bloodstream of COVID-19 patients. Similarly, platelets isolated from COVID-19 patients demonstrate increased reactivity in response to collagen, thrombin, and ADP. By contrast, an analysis of whole blood from COVID-19 patients indicates the reduced activation of the fibrinogen receptor. Similarly, some in vitro studies report potential targets for SARS-CoV-2 in platelets, whereas others do not indicate any direct effect of the virus on platelets. The aim of this work is to review and evaluate the reliability of the methodology for testing platelet function after contact with SARS-CoV-2. Despite the diversity of methods yielding varying results and the influence of plasma components or blood cells, it can be concluded that platelets play an important role in the development of thrombotic complications after exposure to SARS-CoV-2.}, } @article {pmid39791670, year = {2025}, author = {Berti, LC and Gauy, M and da Silva, LCS and Rios, JVV and Morais, VB and Almeida, TC and Sossolete, LS and Quirino, JHM and Martins, CFP and Fernandes-Svartman, FR and Raposo de Medeiros, B and Queiroz, M and Gazzola, M and Finger, M}, title = {Acoustic Characteristics of Voice and Speech in Post-COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/healthcare13010063}, pmid = {39791670}, issn = {2227-9032}, support = {Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; 306919/2023-0//National Council for Scientific and Technological Development/ ; 2023/00488-5; 2022/16374-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {BACKGROUND/OBJECTIVES: The aim of this paper was to compare voice and speech characteristics between post-COVID-19 and control subjects. The hypothesis was that acoustic parameters of voice and speech may differentiate subjects infected by COVID-19 from control subjects. Additionally, we expected to observe the persistence of symptoms in women.

METHODS: In total, 134 subjects participated in the study, were selected for convenience and divided into two groups: 70 control subjects and 64 post-COVID-19 subjects, with an average time of 8.7 months after infection. The recordings were made using the SPIRA software (v.1.0.) on cell phones, based on three verbal tasks: sustained production of the vowel/a/, reading a sentence, and producing a rhyme. Acoustic analyses of speech and voice were carried out with the PRAAT software (v.4.3.18), based on the following parameters: total sentence duration, number of pauses, pause duration, f0, f0SD, jitter, shimmer, and harmonics-to-noise ratio (HNR).

RESULTS: Regarding the acoustic characteristics of speech, there were no differences between the groups or between the sexes. Regarding the acoustic characteristics of voice, jitter, shimmer, and HNR, significant differences between the groups were found. Differences between sexes were observed in the following frequency-related parameters: f0, f0SD, and jitter.

CONCLUSIONS: Some acoustic characteristics of the patients' voice may show a deteriorated condition even after exacerbation of the disease. These characteristics are compatible with some of the symptoms reported by post-COVID-19 subjects, such as the presence of tension and fatigue. These voice acoustic parameters could be used as biomarkers to screen voice disorders in long-COVID, using artificial intelligence (AI), accelerating the search for diagnosis by specialists.}, } @article {pmid39791609, year = {2024}, author = {Anastácio, ZC and Fernandes, SC and Alves, RF and Antão, CM and Carvalho, PO and Benevides Ferreira, SM and Condessa, MIC}, title = {Relation Between COVID-19 Infection and Vaccine and Menstrual Cycle Changes of Portuguese Adolescents in Higher Education.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/healthcare13010002}, pmid = {39791609}, issn = {2227-9032}, support = {CIEC, University of Minho, UIDB/00317/2020 and UIDP/00317/2020//FCT, Foundation for Science and Technology/ ; }, abstract = {UNLABELLED: In a period globally known as long COVID, several post-acute infection sequelae and vaccination effects have been discussed.

OBJECTIVES: This study aimed to identify the effects of COVID-19 infection and vaccines on the menstrual cycle of adolescents attending higher education and to verify the association between personal health factors and changes in their menstrual cycle after contact with the virus SARS-CoV-2 via infection or via the vaccine.

METHODS: A cross-sectional study was conducted using a questionnaire for data collection, applied online to Portuguese higher education adolescents aged between 18 and 24. The sample included 401 individuals. The statistical analysis of data was performed using SPSS.

RESULTS: More than half of the sample had a COVID-19 infection only once and took two doses of the vaccine. The mRNA Comirnaty 30 µg BioNTech vaccine was administered to 73.1%. The most common menstrual changes were an increase in blood clots, the blood becoming darker, shorter menstrual cycles, scarcer blood flow, and more irregular cycles. Menstrual changes correlated significantly with vaccination but not with infection.

CONCLUSIONS: This study showed a lower percentage of women affected than other studies carried out closer to the pandemic period, which could mean that the effects are diminishing over time. Thus, adolescents' menstrual health should be monitored.}, } @article {pmid39790367, year = {2025}, author = {Kuon, CP}, title = {I'm Not the Doctor for You: Cognitive Bias, Complex Illness, and a Moral Imperative.}, journal = {Global advances in integrative medicine and health}, volume = {14}, number = {}, pages = {27536130241311594}, pmid = {39790367}, issn = {2753-6130}, abstract = {Cognitive Bias and the Treatment of Complex Illnesses: A Reflection on Substance Use Disorder and Long COVID. Physicians use anchoring and confirmation bias every day to make snap decisions about patient care. However, in the case of poorly understood complex illness, cognitive bias can lead to poor outcomes for the patient. This article explores how recognizing and overcoming cognitive bias leads to increased personal career satisfaction, and improved patient outcomes. In an era where health disparities are increasingly recognized, and in the post-COVID era in particular, there's a need to recognize cognitive bias against complex illnesses such as Long COVID and Chronic Fatigue Syndrome. It may even be a moral imperative.}, } @article {pmid39789478, year = {2025}, author = {Du, M and Yang, P and Li, M and Yu, X and Wang, S and Li, T and Huang, C and Liu, M and Song, C and Liu, J}, title = {Effects of sleep quality on the risk of various long COVID symptoms among older adults following infection: an observational study.}, journal = {BMC geriatrics}, volume = {25}, number = {1}, pages = {20}, pmid = {39789478}, issn = {1471-2318}, support = {C202012016//Yunnan Province-Chunchenjihua/ ; XDYC-MY-2022-0071//Yunnan Province-Xingdian talent support program/ ; 71934002, 72122001//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Aged ; Female ; *Sleep Quality ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; China/epidemiology ; Risk Factors ; Sleep Wake Disorders/epidemiology ; Prevalence ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The long-term sequelae of coronavirus disease 2019 (COVID-19) and its recovery have becoming significant public health concerns. Therefore, this study aimed to enhance the limited evidence regarding the relationship between sleep quality on long COVID among the older population aged 60 years or old.

METHODS: Our study included 4,781 COVID-19 patients enrolled from April to May 2023, based on the Peking University Health Cohort. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) scale. Long COVID was evaluated by well-trained health professionals through patients' self-reported symptoms. Binary logistic regression models were employed to calculate odds ratios (OR) and 95% confidence intervals (95% CI).

RESULTS: The prevalence of long COVID among older adults was 57.4% (2,743/4,781). Specifically, the prevalence of general symptoms, cardiovascular symptoms, respiratory symptoms, gastrointestinal symptoms, and neurological and psychiatric symptoms was 47.7% (2,282/4,781), 3.4% (163/4,781), 35.2% (1683/4,781), 8.7% (416/4,781) and 5.8% (279/4,781), respectively. For each one-point increase in PSQI scores, the risk of long COVID, general symptoms, cardiovascular symptoms, gastrointestinal symptoms, and neurological and psychiatric symptoms increased by 3% (95% CI: 1.01, 1.06), 3% (95% CI: 1.01, 1.06), 7% (95% CI: 1.01, 1.13), 11% (95% CI: 1.07, 1.15), and 20% (95% CI: 1.15, 1.25), respectively. In multivariate models, compared with good sleepers, COVID-19 patients with poor sleep quality exhibited an increased risk of general symptoms (aOR = 1.17; 95% CI: 1.03, 1.33), cardiovascular symptoms (aOR = 1.50; 95% CI: 1.06, 2.14), gastrointestinal symptoms (aOR = 2.03; 95% CI: 1.61, 2.54), and neurological and psychiatric symptoms (aOR = 2.57; 95% CI = 1.96, 3.37).

CONCLUSIONS: Our findings indicate that poor sleep quality is related to various manifestations of long COVID in older populations. A comprehensive assessment and multidisciplinary management of sleep health and long COVID may be essential to ensure healthy aging in the future.}, } @article {pmid39787064, year = {2025}, author = {Jacobs, JJL and Beekers, I and Verkouter, I and Richards, LB and Vegelien, A and Bloemsma, LD and Bongaerts, VAMC and Cloos, J and Erkens, F and Gradowska, P and Hort, S and Hudecek, M and Juan, M and Maitland-van der Zee, AH and Navarro-Velázquez, S and Ngai, LL and Rafiq, QA and Sanges, C and Tettero, J and van Os, HJA and Vos, RC and de Wit, Y and van Dijk, S}, title = {A data management system for precision medicine.}, journal = {PLOS digital health}, volume = {4}, number = {1}, pages = {e0000464}, pmid = {39787064}, issn = {2767-3170}, abstract = {Precision, or personalised medicine has advanced requirements for medical data management systems (MedDMSs). MedDMS for precision medicine should be able to process hundreds of parameters from multiple sites, be adaptable while remaining in sync at multiple locations, real-time syncing to analytics and be compliant with international privacy legislation. This paper describes the LogiqSuite software solution, aimed to support a precision medicine solution at the patient care (LogiqCare), research (LogiqScience) and data science (LogiqAnalytics) level. LogiqSuite is certified and compliant with international medical data and privacy legislations. This paper evaluates a MedDMS in five types of use cases for precision medicine, ranging from data collection to algorithm development and from implementation to integration with real-world data. The MedDMS is evaluated in seven precision medicine data science projects in prehospital triage, cardiovascular disease, pulmonology, and oncology. The P4O2 consortium uses the MedDMS as an electronic case report form (eCRF) that allows real-time data management and analytics in long covid and pulmonary diseases. In an acute myeloid leukaemia, study data from different sources were integrated to facilitate easy descriptive analytics for various research questions. In the AIDPATH project, LogiqCare is used to process patient data, while LogiqScience is used for pseudonymous CAR-T cell production for cancer treatment. In both these oncological projects the data in LogiqAnalytics is also used to facilitate machine learning to develop new prediction models for clinical-decision support (CDS). The MedDMS is also evaluated for real-time recording of CDS data from U-Prevent for cardiovascular risk management and from the Stroke Triage App for prehospital triage. The MedDMS is discussed in relation to other solutions for privacy-by-design, integrated data stewardship and real-time data analytics in precision medicine. LogiqSuite is used for multi-centre research study data registrations and monitoring, data analytics in interdisciplinary consortia, design of new machine learning / artificial intelligence (AI) algorithms, development of new or updated prediction models, integration of care with advanced therapy production, and real-world data monitoring in using CDS tools. The integrated MedDMS application supports data management for care and research in precision medicine.}, } @article {pmid39781525, year = {2025}, author = {Peramaiyan, R and Anthony, J and Varalakshmi, S and Sekar, AK and Ali, EM and A, AHS and Abdallah, BM}, title = {Comparison of the role of vitamin D in normal organs and those affected by COVID-19.}, journal = {International journal of medical sciences}, volume = {22}, number = {2}, pages = {240-251}, pmid = {39781525}, issn = {1449-1907}, mesh = {Humans ; *COVID-19/immunology ; *Vitamin D ; *Vitamin D Deficiency/immunology/complications ; *SARS-CoV-2/immunology ; Dietary Supplements ; }, abstract = {The outbreak of COVID-19 has opened up new avenues for exploring the importance of vitamin D in immunity, in addition to its role in calcium absorption. Recently, vitamin D supplementation has been found to enhance T regulatory lymphocytes, which are reduced in individuals with COVID-19. Increased risk of pneumonia and increases in inflammatory cytokines have been reported to be major threats associated with vitamin-D deficiency. Although vaccination reduces the threat of COVID-19 to a certain extent, herd immunity is the long-term solution to overcoming such diseases. Co-administration of vitamin D with certain inactivated vaccines has been reported to enhance the systemic immune response through stimulation of the production of antigen-specific mucosal immunity. COVID-19 was found to induce multiple organ damage, and vitamin D has a beneficial role in various organs, such as the intestines, pancreas, prostate, kidneys, liver, heart, brain, and immune cells. The consequences that occur after COVID-19 infection known as long COVID-19 are also a concern as they accumulate and target multiple organs, leading to immune dysregulation. The present review covers the overall role and impact of vitamin D and its deficiency for various organs in normal conditions and after COVID-19 infection, which is still a serious issue.}, } @article {pmid39779922, year = {2025}, author = {Combet, E and Haag, L and Richardson, J and Haig, CE and Cunningham, Y and Fraser, HL and Brosnahan, N and Ibbotson, T and Ormerod, J and White, C and McIntosh, E and O'Donnell, CA and Sattar, N and McConnachie, A and Lean, MEJ and Blane, DN}, title = {Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {39779922}, issn = {1546-170X}, support = {COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; COV-LT2-0059//DH | National Institute for Health Research (NIHR)/ ; }, abstract = {Long COVID (LC) is a complex multisymptom condition with no known disease-modifying treatments. This wait-list-controlled open-label trial tested whether a remotely delivered structured weight management program could improve respective LC symptoms in people living with overweight. Adults with LC (symptoms >12 weeks) and body mass index >27 kg m[-2] (>25 kg m[-2] for South Asians) were randomized (n = 234, 1:1) to control (n = 116, usual care) or the remotely delivered structured weight management (n = 118, total diet replacement (850 kcal per day) for 12 weeks, followed by food reintroduction and weight loss maintenance support) via minimization and randomization (80:20) to balance dominant LC symptom, sex, age, ethnicity and postcode-based index of multiple deprivation between groups. The control group received the intervention after 6 months. Participants selected the dominant LC symptom they would most like to improve (fatigue, breathlessness, pain, anxiety/depression or other) as the prespecified respective primary outcome. Individual symptoms were assessed using validated questionnaires and a visual analog scale for those without prespecified scales. At 6 months, the primary outcome improved in the intervention group (change -1.16 (s.d. 1.42), n = 97 analyzed) compared with the control group (change -0.83 (s.d. 1.14), n = 117 analyzed) with a treatment effect of -0.34 (95% confidence interval -0.67 to -0.01), with no excess of serious adverse events. International Standard Randomised Controlled Trial Number Registry registration: ISRCTN 12595520 .}, } @article {pmid39778322, year = {2024}, author = {Dal-Pizzol, F and Kluwe-Schiavon, B and Dal-Pizzol, HR and da Silveira Prestes, G and Dominguini, D and Girardi, CS and Santos, L and Moreira, JCF and Gelain, DP and Walz, R and Barichello, T and Ritter, C}, title = {Association of systemic inflammation and long-term dysfunction in COVID-19 patients: A prospective cohort.}, journal = {Psychoneuroendocrinology}, volume = {172}, number = {}, pages = {107269}, doi = {10.1016/j.psyneuen.2024.107269}, pmid = {39778322}, issn = {1873-3360}, abstract = {COVID-19 has significant long-term impacts, including a chronic syndrome known as long-COVID, characterized by persistent symptoms post-recovery. The inflammatory response during acute infection is hypothesized to influence long-term outcomes. This study aimed to identify inflammatory biomarkers predictive of functional outcomes one year after hospital discharge. A prospective cohort study was conducted with 213 COVID-19 patients admitted to ICUs in Southern Brazil between June and November 2020. After exclusions and follow-ups, 109 patients were evaluated for one-year post-discharge. Plasma levels of Th1 (TNF-α, INF-γ, IL-12), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17, IL-22) cytokines were measured. Functional outcomes in psychiatric, cognitive, general health, and health perception domains were assessed. Statistical analyses included multivariate regression, regularized partial correlation network analysis, and K-means clustering. We demonstrate that plasma levels of various cytokines, along with demographic and clinical characteristics, can predict four distinct domains of functional outcomes one year following hospital discharge due to COVID-19 and that an hyperinflammatory phenotype was associated with the occurrence of a worse in psychiatric, general health, and health perception domains. The network analysis highlighted complex interconnections among immune markers and clinical variables, elucidating their roles in long-term health. These findings support using biomarkers for patient stratification and indicate potential targets for therapeutic interventions.}, } @article {pmid39777702, year = {2025}, author = {Fekete, M and Lehoczki, A and Szappanos, Á and Toth, A and Mahdi, M and Sótonyi, P and Benyó, Z and Yabluchanskiy, A and Tarantini, S and Ungvari, Z}, title = {Cerebromicrovascular mechanisms contributing to long COVID: implications for neurocognitive health.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39777702}, issn = {2509-2723}, support = {RRF-2.3.1-21-2022-00003//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; TKP2021-NKTA-47//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; }, abstract = {Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.}, } @article {pmid39777257, year = {2025}, author = {Mukherjee, S and Singer, T and Venkatesh, A and Choudhury, NA and Perez Giraldo, GS and Jimenez, M and Miller, J and Lopez, M and Hanson, BA and Bawa, AP and Batra, A and Liotta, EM and Koralnik, IJ}, title = {Vaccination prior to SARS-CoV-2 infection does not affect the neurologic manifestations of long COVID.}, journal = {Brain communications}, volume = {7}, number = {1}, pages = {fcae448}, pmid = {39777257}, issn = {2632-1297}, abstract = {Persistent symptoms after COVID-19 constitute the long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). COVID-19 vaccines reduce the gravity of ensuing SARS-CoV-2 infections. However, whether vaccines also have an impact on PASC remain unknown. We investigated whether vaccination prior to infection alters the subsequent neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). We studied prospectively the first consecutive 200 post-hospitalization Neuro-PASC (PNP) and 1100 non-hospitalized Neuro-PASC (NNP) patients evaluated at our neuro-COVID-19 clinic between May 2020 and January 2023. Among PNP patients, 87% had a pre-vaccination infection and 13% had a breakthrough infection post-vaccination. Among the NNP patients, 70.7% had a pre-vaccination infection and 29.3% had a breakthrough infection. Both PNP and NNP breakthrough infection patients had more frequent pre-existing depression/anxiety than their respective pre-vaccination infection groups, and NNP breakthrough infection patients also had more frequent comorbidities of headache, lung and gastrointestinal diseases than the NNP pre-vaccination infection group. An average of 10 months after symptom onset, the three most common neurological symptoms for PNP patients were brain fog (86.5%), numbness/tingling (56.5%) and headache (56.5%). Of all Neuro-PASC symptoms, PNP breakthrough infection more frequently reported anosmia compared to PNP pre-vaccination infection patients (69.2 versus 37.9%; P = 0.005). For NNP patients, the three most common neurological symptoms were brain fog (83.9%), headache (70.9%) and dizziness (53.8%). NNP pre-vaccination infection reported anosmia (56.6 versus 39.1%; P < 0.0001) and dysgeusia (53.3 versus 37.3%; P < 0.0001) more frequently than breakthrough infection patients. NNP breakthrough infection more frequently reported dizziness compared to NNP pre-vaccination infection patients (61.5 versus 50.6%; P = 0.001). Both PNP and NNP patients had impaired quality-of-life in cognitive, fatigue, sleep, anxiety and depression domains with no differences between pre-vaccination infection and breakthrough infection groups. PNP patients performed worse on National Institutes of Health Toolbox tests of processing speed, attention, executive function and working memory than a US normative population whereas NNP patients had lower results in processing, speed, attention and working memory, without differences between pre-vaccination infection and breakthrough infection groups. These results indicate that vaccination prior to SARS-CoV-2 infection does not affect the neurologic manifestations of long COVID in either PNP or NNP patients. Minor differences in neurologic symptoms between pre-vaccination infection and breakthrough infection groups may be caused by SARS-CoV-2 strains evolution. Patients developing Neuro-PASC after breakthrough infection have a higher burden of comorbidities, highlighting different risk factors warranting targeted management.}, } @article {pmid39775442, year = {2025}, author = {Giannakopoulos, S and Pak, J and Bakse, J and Ward, MA and Nerurkar, VR and Tallquist, MD and Verma, S}, title = {SARS-CoV-2-induced cytokine storm drives prolonged testicular injury and functional impairment in mice that are mitigated by dexamethasone.}, journal = {PLoS pathogens}, volume = {21}, number = {1}, pages = {e1012804}, pmid = {39775442}, issn = {1553-7374}, mesh = {Animals ; Male ; Mice ; *COVID-19/complications/immunology ; *Dexamethasone/pharmacology/therapeutic use ; *Testis/pathology/virology/drug effects/metabolism ; *SARS-CoV-2 ; *Cytokine Release Syndrome/drug therapy ; Testosterone ; Disease Models, Animal ; COVID-19 Drug Treatment ; Humans ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {Compromised male reproductive health, including reduced testosterone and sperm count, is one of the long COVID symptoms in individuals recovering from mild-severe disease. COVID-19 patients display testicular injury in the acute stage and altered serum fertility markers in the recovery phase, however, long-term implications on the testis remain unknown. This study characterized the consequences of SARS-CoV-2 on testis function. The K18-hACE2 mice that survived SARS-CoV-2 infection were followed for one month after infection and the testicular injury and function markers were assessed at different stages of infection and recovery. The long-term impact of infection on key testes function-related hormones and male fertility was measured. The efficacy of inflammation-suppressing drug in preventing testicular injury was also evaluated. The morphological defects like sloughing of spermatids into the lumen and increased apoptotic cells sustained for 2-4 weeks after infection and correlated with testicular inflammation and immune cell infiltration. Transcriptomic analysis revealed dysregulation of inflammatory, cell death, and steroidogenic pathways. Furthermore, reduced testosterone levels associated with a transient reduction in sperm count and male fertility. Most testicular impairments resolved within one month of infection. Importantly, dexamethasone treatment attenuated testicular damage, inflammation, and immune infiltration. Our results implicate virus-induced cytokine storm as the major driver of testicular injury and functional impairments, timely prevention of which limits testis damage. These findings serve as a model for evaluating therapeutics in long COVID patients and may guide clinical strategies to improve male reproductive health outcomes post-SARS-CoV-2 infection.}, } @article {pmid39773837, year = {2025}, author = {Artemiadis, A and Tofarides, AG and Liampas, A and Ioannou, C and Christodoulou, K and Louka, R and Vavougios, G and Zis, P and Bargiotas, P and Hadjigeorgiou, G}, title = {Factors associated with quality of life in long-COVID syndrome.}, journal = {International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation}, volume = {}, number = {}, pages = {}, doi = {10.1097/MRR.0000000000000654}, pmid = {39773837}, issn = {1473-5660}, abstract = {Approximately 10% of patients experience persistent symptoms following COVID-19, known as long-COVID syndrome. This cross-sectional study explored factors of quality of life (QoL) in 53 long-COVID patients. QoL was measured using the World Health Organization-Five Well-Being Index, fatigue with the Fatigue Visual Analogue Scale, and psychological health with the Depression-Anxiety-Stress-21 questionnaire. Six neuropsychological tests assessed information processing speed, verbal memory, visual memory, working memory, attention, language, fluency, recall, and visuospatial function with a composite score calculated by averaging z scores. Patients (76% female, mean age: 54.1 years) were assessed 8.7 months postinfection. Cognitive impairment, present in 49% of the sample, was not associated with QoL. In multiple linear regression, gender, fatigue, and psychological distress accounted for 42% of QoL variance, with fatigue and distress contributing 7% and 11%, respectively. Further studies are needed to determine if fatigue and psychological distress are causally related to QoL in long-COVID and could be treatment targets.}, } @article {pmid39772268, year = {2024}, author = {Valkov, T and Argirova, R and Dimitrov, G}, title = {SARS-CoV-2 Infection of the Central Nervous System: A Case Report.}, journal = {Viruses}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/v16121962}, pmid = {39772268}, issn = {1999-4915}, mesh = {Humans ; Female ; *COVID-19/complications/diagnosis ; *SARS-CoV-2 ; Aged, 80 and over ; }, abstract = {Central nervous system (CNS) infections caused by SARS-CoV-2 are uncommon. This case report describes the clinical progression of a 92-year-old female who developed a persistent neuroinfection associated with SARS-CoV-2. The patient initially presented with progressive fatigue, catarrhal symptoms, and a fever (38.6 °C). Initial laboratory findings revealed hypoxemia (O2 saturation 79.8%), acidosis (pH 7.3), an elevated C-reactive protein (CRP) level of 14.8 mg/L, and a high D-dimer level (2.15 µg/mL). Nasopharyngeal (NP) antigen and RT-PCR tests confirmed SARS-CoV-2 infection, and an NP swab also detected penicillin- and ampicillin-resistant Staphylococcus aureus. She was admitted for conservative management, including oxygen supplementation, IV fluids, and prophylactic anticoagulation. Subsequently, she developed neurological symptoms-lethargy, discoordination, and impaired communication-without signs of meningism. Cerebrospinal fluid (CSF) analysis identified SARS-CoV-2 RNA (Ct = 29) on RT-PCR, while bacterial cultures remained negative. Treatment was intensified to include 10% mannitol, dexamethasone, and empiric ceftriaxone. Despite these interventions, the patient remained somnolent, with a Glasgow Coma Scale (GCS) score of 10. Upon discharge, her GCS had improved to 14; however, she continued to experience lethargy and cognitive issues, commonly described as "brain fog". Inflammatory markers remained elevated (CRP 23 mg/L) and repeat RT-PCR of CSF confirmed a persistent SARS-CoV-2 presence (Ct = 31). This case underscores the potential for SARS-CoV-2 to cause prolonged CNS involvement, leading to persistent neurological impairment despite standard therapy. Further research is essential to clarify the pathophysiology of and determine optimal management for SARS-CoV-2 neuroinfections.}, } @article {pmid39772261, year = {2024}, author = {Joseph, G and Margalit, I and Weiss-Ottolenghi, Y and Rubin, C and Murad, H and Gardner, RC and Barda, N and Ben-Shachar, E and Indenbaum, V and Gilboa, M and Alroy-Preis, S and Kreiss, Y and Lustig, Y and Regev-Yochay, G}, title = {Persistence of Long COVID Symptoms Two Years After SARS-CoV-2 Infection: A Prospective Longitudinal Cohort Study.}, journal = {Viruses}, volume = {16}, number = {12}, pages = {}, pmid = {39772261}, issn = {1999-4915}, support = {no grant number//Ministry of Health Israel/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Middle Aged ; Female ; Male ; Adult ; *SARS-CoV-2/immunology ; Aged ; Longitudinal Studies ; Prospective Studies ; Young Adult ; Biomarkers/blood ; Adolescent ; Post-Acute COVID-19 Syndrome ; Antibodies, Viral/blood ; Antibodies, Neutralizing/blood ; Prevalence ; Surveys and Questionnaires ; }, abstract = {BACKGROUND/OBJECTIVES: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID-including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell-that have persisted for at least two years after acute infection, which we define as "persistent Long COVID". Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms.

METHODS: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18-79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz-Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID.

RESULTS: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7-26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID.

CONCLUSIONS: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed.}, } @article {pmid39772223, year = {2024}, author = {Loutsidi, NE and Politou, M and Vlahakos, V and Korakakis, D and Kassi, T and Nika, A and Pouliakis, A and Eleftheriou, K and Balis, E and Pappas, AG and Kalomenidis, I}, title = {Hypercoagulable Rotational Thromboelastometry During Hospital Stay Is Associated with Post-Discharge DLco Impairment in Patients with COVID-19-Related Pneumonia.}, journal = {Viruses}, volume = {16}, number = {12}, pages = {}, pmid = {39772223}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications/blood ; Male ; Female ; *Thrombelastography ; Middle Aged ; Prospective Studies ; Aged ; *Thrombophilia/etiology/blood ; *SARS-CoV-2 ; Patient Discharge ; Hospitalization ; Blood Coagulation ; }, abstract = {Hypercoagulation is central to the pathogenesis of acute and post-acute COVID-19. This prospective observational study explored whether rotational thromboelastometry (ROTEM), a method that unveils coagulation status, predicts outcomes of hospitalized patients with COVID-19 pneumonia. We investigated 62 patients using ROTEM that was conducted at enrollment, clinical deterioration, discharge and follow-up visits 1 and 3 months post-discharge. A hypercoagulable ROTEM was more common at clinical deterioration than at enrollment and the levels of hypercoagulable ROTEM indices correlated with the clinical severity score. Hypercoagulable ROTEM at enrollment was not associated with in-hospital death. Patients with hypercoagulable ROTEM at enrollment, discharge and 1 month post-discharge had an increased risk of persistent symptoms 1 and 3 months after discharge. Patients with hypercoagulable ROTEM at enrollment, discharge, and 1 month after discharge were more likely to have lung diffusion capacity (DLco) impairment 3 months after discharge. High levels of hypercoagulable ROTEM indices were associated with the increased risk of persistent symptoms at later stages of the disease. In a multivariate analysis, (i) hypercoagulable ROTEM at discharge and female gender were linked to the presence of symptoms at one month post-discharge, (ii) hypercoagulable ROTEM at one month after discharge was linked to the presence of symptoms at three months post-discharge, (iii) hypercoagulable ROTEM at enrollment and at discharge and female gender were linked to the presence of impaired DLco at three months post-discharge. Excessive coagulation may contribute to long-COVID pathogenesis and ROTEM findings during hospitalization may predict post-acute-COVID-19 sequelae in patients with COVID-19-related pneumonia.}, } @article {pmid39772122, year = {2024}, author = {Pacnejer, AM and Butuca, A and Dobrea, CM and Arseniu, AM and Frum, A and Gligor, FG and Arseniu, R and Vonica, RC and Vonica-Tincu, AL and Oancea, C and Mogosan, C and Popa Ilie, IR and Morgovan, C and Dehelean, CA}, title = {Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies.}, journal = {Viruses}, volume = {16}, number = {12}, pages = {}, pmid = {39772122}, issn = {1999-4915}, support = {LBUS-IRG-2023/No. 3523, 24 July 2023//Lucian Blaga University of Sibiu/ ; }, mesh = {Humans ; *COVID-19/physiopathology/psychology/virology ; *SARS-CoV-2 ; Mental Disorders/therapy/etiology ; Nervous System Diseases/virology/physiopathology ; Angiotensin-Converting Enzyme 2/metabolism ; }, abstract = {The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.}, } @article {pmid39772087, year = {2024}, author = {Quach, TC and Miglis, MG and Tian, L and Bonilla, H and Yang, PC and Grossman, L and Paleru, A and Xin, V and Tiwari, A and Shafer, RW and Geng, LN}, title = {Post-COVID-19 Vaccination and Long COVID: Insights from Patient-Reported Data.}, journal = {Vaccines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/vaccines12121427}, pmid = {39772087}, issn = {2076-393X}, abstract = {INTRODUCTION: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed.

METHODS: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484).

FINDINGS: Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort.

CONCLUSIONS: Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC.}, } @article {pmid39772040, year = {2024}, author = {Platschek, B and Boege, F}, title = {The Post-Acute COVID-19-Vaccination Syndrome in the Light of Pharmacovigilance.}, journal = {Vaccines}, volume = {12}, number = {12}, pages = {}, pmid = {39772040}, issn = {2076-393X}, abstract = {Background/Objectives: Clinical studies show that SARS-CoV-2 vaccination sometimes entails a severe and disabling chronic syndrome termed post-acute-COVID-19-vaccination syndrome (PACVS). PACVS shares similarities with long COVID. Today, PACVS is still not officially recognised as a disease. In contrast, long COVID was registered by health authorities in December 2021. Here, we address possible reasons for that discrepancy. Methods: We analyse whether common symptoms of PACVS have been registered by European pharmacovigilance as adverse vaccination reactions and which consequences have been drawn thereof. Results: (i) PACVS is distinguished from normal vaccination reactions solely by prolonged duration. (ii) Symptom duration is poorly monitored by post-authorisation pharmacovigilance. (iii) PACVS-specific signals were faithfully recorded by pharmacovigilance systems but have not prompted appropriate reactions of health authorities. (iv) The most widely applied SARS-CoV-2 mRNA-vaccine has been modified after roll-out without renewed phase III evaluation; the modification has increased DNA contaminations suspected to extend the spectrum of adverse events. (v) Crossing of pharmacovigilance data with corresponding estimates of applied vaccine doses suggest a PACVS prevalence of 0.003% in the general population. In contrast, occupational surveillance studies suggest a PACVS prevalence of 0.9% in young and middle-aged persons. Conclusions: (a) Denial of official recognition of PACVS is unjustified. (b) PACVS seems to target preferentially young and middle-aged persons. (c) Without official disease recognition, access to public healthcare and welfare services is made difficult for PACVS-affected persons, which creates considerable socio-economic problems. (d) Without official disease recognition, development and evaluation of PACVS therapies is impaired.}, } @article {pmid39770368, year = {2024}, author = {Nakayama, EE and Shioda, T}, title = {Detrimental Effects of Anti-Nucleocapsid Antibodies in SARS-CoV-2 Infection, Reinfection, and the Post-Acute Sequelae of COVID-19.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/pathogens13121109}, pmid = {39770368}, issn = {2076-0817}, support = {JM00000160//Center for Infectious Disease Education and Research, CiDER/ ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology ; *Reinfection/immunology/virology ; *Antibodies, Neutralizing/immunology ; *Antibody-Dependent Enhancement/immunology ; Cytokines/immunology/metabolism ; Receptors, Fc/immunology ; Nucleocapsid/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing antibodies in individuals infected with dengue virus are known to be associated with severe disease upon reinfection with a different dengue virus serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types of ADE have been proposed: (1) Fc receptor-dependent ADE of infection in cells expressing Fc receptors, such as macrophages by anti-spike antibodies, (2) Fc receptor-independent ADE of infection in epithelial cells by anti-spike antibodies, and (3) Fc receptor-dependent ADE of cytokine production in cells expressing Fc receptors, such as macrophages by anti-nucleocapsid antibodies. This review focuses on the Fc receptor-dependent ADE of cytokine production induced by anti-nucleocapsid antibodies, examining its potential role in severe COVID-19 during reinfection and its contribution to the post-acute sequelae of COVID-19, i.e., prolonged symptoms lasting at least three months after the acute phase of the disease. We also discuss the protective effects of recently identified anti-spike antibodies that neutralize Omicron variants.}, } @article {pmid39768836, year = {2024}, author = {Strumiliene, E and Urbonienė, J and Jurgauskiene, L and Zeleckiene, I and Bliudzius, R and Malinauskiene, L and Zablockiene, B and Samuilis, A and Jancoriene, L}, title = {Long-Term Pulmonary Sequelae and Immunological Markers in Patients Recovering from Severe and Critical COVID-19 Pneumonia: A Comprehensive Follow-Up Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {12}, pages = {}, pmid = {39768836}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/immunology/complications/physiopathology/diagnostic imaging ; Middle Aged ; Male ; Female ; Prospective Studies ; Follow-Up Studies ; *Respiratory Function Tests ; Lithuania ; *SARS-CoV-2 ; *Lung/diagnostic imaging/physiopathology ; Tomography, X-Ray Computed ; Biomarkers/blood ; Vital Capacity ; Aged ; Severity of Illness Index ; }, abstract = {Background and Objectives: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological changes, and some immune parameters in survivors of severe and critical COVID-19 up to 12 months after hospital discharge. Materials and Methods: This prospective observational cohort study followed 85 adult patients who were hospitalized with severe or critical COVID-19 pneumonia at a tertiary care hospital in Vilnius, Lithuania, for 12 months post-discharge. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusion capacity for carbon monoxide (DLCO), were conducted at 3, 6, and 12 months. High-resolution chest computed tomography (CT) scans assessed residual inflammatory and profibrotic/fibrotic abnormalities. Lymphocyte subpopulations were evaluated via flow cytometry during follow-up visits to monitor immune status. Results: The median age of the cohort was 59 years (IQR: 51-64). Fifty-three (62.4%) patients had critical COVID-19 disease. Pulmonary function improved significantly over time, with increases in FVC, FEV1, VC, TLC, and DLCO. Residual volume (RV) did not change significantly over time, suggesting that some aspects of lung function, such as air trapping, remained stable and may require attention in follow-up care. The percentage of patients with restrictive spirometry patterns decreased from 24.71% at 3 months to 14.8% at 12 months (p < 0.05). Residual inflammatory changes on CT were present in 77.63% at 6 months, decreasing to 69.62% at 12 months (p < 0.001). Profibrotic changes remained prevalent, affecting 82.89% of patients at 6 months and 73.08% at 12 months. Lymphocyte counts declined significantly from 3 to 12 months (2077 cells/µL vs. 1845 cells/µL, p = 0.034), with notable reductions in CD3+ (p = 0.040), CD8+ (p = 0.007), and activated CD3HLA-DR+ cells (p < 0.001). This study found that higher CD4+ T cell counts were associated with worse lung function, particularly reduced total lung capacity (TLC), while higher CD8+ T cell levels were linked to improved pulmonary outcomes, such as increased forced vital capacity (FVC) and vital capacity (VC). Multivariable regression analyses revealed that increased levels of CD4+/CD28+/CD192+ T cells were associated with worsening lung function, while higher CD8+/CD28+/CD192+ T cell counts were linked to better pulmonary outcomes, indicating that immune dysregulation plays a critical role in long-term respiratory recovery. Conclusions: Survivors of severe and critical COVID-19 pneumonia continue to experience significant long-term impairments in lung function and immune system health. Regular monitoring of pulmonary function, radiological changes, and immune parameters is essential for guiding personalized post-COVID-19 care and improving long-term outcomes. Further research is needed to explore the mechanisms behind these complications and to develop targeted interventions for long COVID-19.}, } @article {pmid39768752, year = {2024}, author = {Bielecka-Dabrowa, A and Kapusta, J and Sakowicz, A and Banach, M and Jankowski, P and Chudzik, M}, title = {The Influence of Long COVID on the Cardiovascular System and Predictors of Long COVID in Females: Data from the Polish Long COVID Cardiovascular (PoLoCOV-CVD) Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {24}, pages = {}, pmid = {39768752}, issn = {2077-0383}, abstract = {Background/Objectives: Female sex is one of the Long COVID (LC) risk factors; however, the LC predictors in females have not been established. This study was conducted to assess the influence of LC on the cardiovascular system and to assess the age-independent predictors of LC in females. Methods: Patient information and the course of the disease with symptoms were collected in women at least 12 weeks after COVID-19 recovery. The study participants were followed for 12 months. ECG monitoring, 24 h ECG monitoring, 24 h blood pressure monitoring, echocardiography, and biochemical tests were performed. Results: We studied 1946 consecutive female patients (age 53.0 [43.0-63.0] vs. 52.5 [41.0-63.0], p = 0.25). A more frequent occurrence of LC was observed in females with a severe SARS-CoV-2 infection (p = 0.0001). Women with LC compared to the control group had higher body mass index (p = 0.001), lower level of HDL cholesterol (p = 0.015), higher level of TG (p < 0.001) and higher TG/HDL ratio (p < 0.001), more often myocardial damage (p < 0.001), and lower LVEF (p = 0.01). LC women had more often QRS fragmentation, longer QTcB, and one of the ECG abnormalities. In a multivariate analysis in younger females with BMI > 24.8 kg/m[2], TG/HDL ratio > 1.89 and severe course of COVID-19 and in older females, TG/HDL ratio > 1.89, lower LVEF, and also severe course of infection were independent LC predictors. Conclusions: Independent predictors of LC occurrence in women, regardless of age, are severe course of COVID-19 and TG/HDL ratio > 1.89. The presence of comorbidities and lifestyle before COVID-19 had no impact on the occurrence of LC in females regardless of age.}, } @article {pmid39767737, year = {2024}, author = {Malioukis, A and Snead, RS and Marczika, J and Ambalavanan, R}, title = {Pathophysiological, Neuropsychological, and Psychosocial Influences on Neurological and Neuropsychiatric Symptoms of Post-Acute COVID-19 Syndrome: Impacts on Recovery and Symptom Persistence.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767737}, issn = {2227-9059}, abstract = {Although the impact of post-acute COVID-19 syndrome (PACS) on patients and public health is undeniably significant, its etiology remains largely unclear. Much research has been conducted on the pathophysiology, shedding light on various aspects; however, due to the multitude of symptoms and clinical conditions that directly or indirectly define PACS, it is challenging to establish definitive causations. In this exploration, through systematically reviewing the latest pathophysiological findings related to the neurological symptoms of the syndrome, we aim to examine how psychosocial and neuropsychological symptoms may overlap with neurological ones, and how they may not only serve as risk factors but also contribute to the persistence of some primary symptoms of the disorder. Findings from our synthesis suggest that psychological and psychosocial factors, such as anxiety, depression, and loneliness, may interact with neurological symptoms in a self-reinforcing feedback loop. This cycle seems to be affecting both physical and psychological distress, potentially increasing the persistence and severity of PACS symptoms. By pointing out this interaction, in this review study, we attempt to offer a new perspective on the interconnected nature of psychological, psychosocial, and neurological factors, emphasizing the importance of integrated treatment approaches to disrupt this cycle and improve outcomes when possible.}, } @article {pmid39767601, year = {2024}, author = {Baalbaki, N and Verbeek, ST and Bogaard, HJ and Blankestijn, JM and van den Brink, VC and Cornelissen, MEB and Twisk, JWR and Golebski, K and Maitland-van der Zee, AH and , }, title = {Pharmacotherapy from Pre-COVID to Post-COVID: Longitudinal Trends and Predictive Indicators for Long COVID Symptoms.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, pmid = {39767601}, issn = {2227-9059}, support = {LSHM20104; LSHM20068//Health-Holland, Top Sector Life Sciences & Health/ ; }, abstract = {BACKGROUND/OBJECTIVES: A significant number of COVID-19 cases experience persistent symptoms after the acute infection phase, a condition known as long COVID or post-acute sequelae of COVID-19. Approved prevention and treatment options for long COVID are currently lacking. Given the heterogeneous nature of long COVID, a personalized medicine approach is essential for effective disease management. This study aimed to describe trends in pharmacotherapy from pre-COVID to post-COVID phases to gain insights into COVID-19 treatment strategies and assess whether pre-COVID pharmacotherapy can predict long COVID symptoms as a health status indicator.

METHODS: In the Precision Medicine for more Oxygen (P4O2) COVID-19 study, 95 long COVID patients were comprehensively evaluated through post-COVID outpatient clinics and study visits. This study focused on descriptive analysis of the pharmacotherapy patterns across different phases: pre-COVID-19, acute COVID, and post-COVID. Furthermore, associations between pre-COVID medication and long COVID outcomes were analyzed with regression analyses.

RESULTS: We observed peaks in the use of certain medications during the acute infection phase, including corticosteroids and antithrombotic agents, with a decrease in the use of renin-angiotensin system inhibitors. Consistently high use of alimentary tract medications was found across all phases. Pre-COVID respiratory medications were associated with fatigue symptoms, while antiinfectives and cardiovascular drugs were linked to fewer persisting long COVID symptom categories.

CONCLUSION: Our findings provide longitudinal, descriptive pharmacotherapy insights and suggest that medication history can be a valuable health status indicator in characterizing patients for personalized disease management strategies, considering the heterogeneous nature of long COVID.}, } @article {pmid39767173, year = {2024}, author = {Lazar, M and Barbu, EC and Chitu, CE and Buzoianu, M and Petre, AC and Tiliscan, C and Arama, SS and Arama, V and Ion, DA and Olariu, MC}, title = {Surviving COVID-19 and Battling Fibrosis: A Retrospective Cohort Study Across Three Pandemic Waves.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, pmid = {39767173}, issn = {2075-4418}, abstract = {BACKGROUND/OBJECTIVES: We aimed to characterize the fibrosis following COVID-19 pneumonia, using quantitative analysis, after three months and subsequently, after two years of patients' release from the hospital, and to identify the risk factors for pulmonary fibrosis.

METHODS: We performed a retrospective, observational cohort study on 420 patients with severe forms of COVID-19. For all patients, we registered demographic, inflammatory and biochemical parameters, complete blood count and D-dimers; all patients underwent three computed tomography scans (at admittance, at 3 months and at 2 years).

RESULTS: We found fibrosis in 67.9% of patients at the 3-month evaluation and in 42.4% of patients at the 2-year evaluation, registering a significant decrease in the severe and moderate fibrosis cases, with a slight increase in the mild fibrosis cases. The risk of fibrosis was found to be proportional to the values of age, duration of hospital stay, inflammatory markers (ESR, fibrinogen), cytolytic markers (LDH, AST) and D-dimers. The highest correlations with lung fibrosis were registered for interstitial pulmonary involvement (for the 3-month evaluation) and total pulmonary involvement (for the 2-year evaluation).

CONCLUSIONS: Lung fibrosis represents a significant post-COVID-19 complication found in 42% of patients with severe forms of pneumonia at the 2-year evaluation. A significant overall decrease in the severity of lung fibrosis was registered at the 2-year evaluation compared to the 3-month evaluation. We consider that the amount of interstitial pulmonary involvement represents the optimal parameter to estimate the risk of lung fibrosis following SARS-CoV-2 pneumonia.}, } @article {pmid39767163, year = {2024}, author = {Gul Ates, E and Coban, G and Karakaya, J}, title = {Diagnostic Models for Differentiating COVID-19-Related Acute Ischemic Stroke Using Machine Learning Methods.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, pmid = {39767163}, issn = {2075-4418}, abstract = {Backgrounds: Although COVID-19 is primarily known as a respiratory disease, there is growing evidence of neurological complications, such as ischemic stroke, in infected individuals. This study aims to evaluate the impact of COVID-19 on acute ischemic stroke (AIS) using radiomic features extracted from brain MR images and machine learning methods. Methods: This retrospective study included MRI data from 57 patients diagnosed with AIS who presented to the Department of Radiology at Hacettepe University Hospital between March 2020 and September 2021. Patients were stratified into COVID-19-positive (n = 30) and COVID-19-negative (n = 27) groups based on PCR results. Radiomic features were extracted from brain MR images following image processing steps. Various feature selection algorithms were applied to identify the most relevant features, which were then used to train and evaluate machine learning classification models. Model performance was evaluated using a range of classification metrics, including measures of predictive accuracy and diagnostic reliability, with 95% confidence intervals provided to enhance reliability. Results: This study assessed the performance of dimensionality reduction and classification algorithms in distinguishing COVID-19-negative and COVID-19-positive cases using radiomics data from brain MR scans. Without feature selection, ANN achieved the highest AUC of 0.857 (95% CI: 0.806-0.900), demonstrating strong discriminative power. Using the Boruta method for feature selection, the k-NN classifier attained the best performance, with an AUC of 0.863 (95% CI: 0.816-0.904). LASSO-based feature selection showed comparable results across k-NN, RF, and ANN classifiers, while SVM exhibited excellent specificity and high PPV. The RFE method yielded the highest overall performance, with the k-NN classifier achieving an AUC of 0.882 (95% CI: 0.838-0.924) and an accuracy of 79.1% (95% CI: 73.6-83.8). Among the methods, RFE provided the most consistent results, with k-NN and the ANN identified as the most effective classifiers for COVID-19 detection. Conclusions: The proposed radiomics-based classification model effectively distinguishes AIS associated with COVID-19 from brain MRI. These findings demonstrate the potential of AI-driven diagnostic tools to identify high-risk patients, support optimized treatment strategies, and ultimately improve clinical implications.}, } @article {pmid39767135, year = {2024}, author = {Pakan, R and Hadidchi, R and Al-Ani, Y and Piskun, H and Duong, KS and Henry, S and Wang, S and Maurer, CW and Duong, TQ}, title = {Long-Term Outcomes of Patients with Pre-Existing Essential Tremor After SARS-CoV-2 Infection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, pmid = {39767135}, issn = {2075-4418}, abstract = {BACKGROUND/OBJECTIVES: Although COVID-19 has been linked to worse outcomes in patients with neurological disorders, its impact on those with essential tremor (ET) remains unclear. To investigate clinical outcomes of ET patients with and without COVID-19 three and a half years post-pandemic.

METHODS: 1074 ET patients were evaluated in this retrospective study in the Montefiore Health System from January 2016 to July 2023. Comparisons between ET patients with and without a positive SARS-CoV-2 polymerase chain reaction test were made. Outcomes included post-index date major adverse cardiovascular events (MACEs), new-onset sleep disturbances, fatigue, dyspnea, first-time fall, new-onset anxiety, new-onset depression, headache, new-onset imbalance, new-onset mild cognitive impairment, and all-cause mortality, adjusted hazard ratios (aHR) adjusting for covariates were calculated.

RESULTS: ET patients with COVID-19 had higher prevalence of pre-existing type-2 diabetes, depression, and anxiety compared to ET patients without COVID-19. COVID-19 was significantly associated with higher risk of MACEs, (aHR = 2.39 [1.49, 3.82]), new-onset sleep disturbance, (aHR = 2.12 [1.44, 3.13]), fatigue, (aHR = 1.83 [1.27, 2.65]), dyspnea, (aHR = 1.98 [1.40, 2.80]), first-time fall, (aHR = 4.76 [2.24, 10.14]), new-onset anxiety, (aHR = 3.66 [2.02, 6.64]), and new-onset depression, (aHR = 2.38 [1.20, 4.70]). COVID-19 was not associated with all-cause mortality.

CONCLUSIONS: In patients with ET, COVID-19 significantly increases the risk of several long-term adverse health outcomes, but not mortality.}, } @article {pmid39766476, year = {2024}, author = {Saak, TM and Tervo, JP and Vilarello, BJ and Jacobson, PT and Caruana, FF and Spence, MDA and Gallagher, LW and Gudis, DA and Motter, JN and Devanand, DP and Overdevest, JB}, title = {Depression, Anxiety, and Neuropsychiatric Symptom Burden in a Longitudinal Cohort with Persistent Psychophysical Post-COVID Olfactory Dysfunction.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766476}, issn = {2076-3425}, support = {K23DC019678; UL1TR001873//National Institute on Deafness and other Communication Disorders (National Institutes of Health); National Center for Advancing Translational Sciences (National Institute of Health, Clinical and Translational Science Award Program at Columbia University I/ ; }, abstract = {BACKGROUND/OBJECTIVES: Olfactory dysfunction (OD) is associated with a variety of neurologic deficits and impacts socialization decisions, mood, and overall quality of life. As a common symptom comprising the long COVID condition, persistent COVID-19-associated olfactory dysfunction (C19OD) may further impact the presentations of neuropsychiatric sequelae. Our study aims to characterize the longitudinal burden of depression, anxiety, and neuropsychiatric symptoms in a population with C19OD.

METHODS: Individuals with perceived C19OD completed a psychophysical screening evaluation of their sense of smell using the comprehensive Sniffin' Sticks olfactory assessment. Only those with validated psychophysical OD were included in this prospective longitudinal study for baseline and one-year follow-up. Participants also completed PHQ-9, Beck Anxiety Inventory (BAI), and neuropsychiatric symptom questionnaires at each time point. Anxiety, depression, and neuropsychiatric symptom prevalence was calculated and compared between time points with Pearson's chi-squared, Fisher's exact, and Wilcoxon rank sum tests.

RESULTS: Each neuropsychiatric symptom evaluated in this study was reported by 13-49% of longitudinal cohort participants at both baseline and follow-up, except for seizure (0% at baseline and follow-up) and word-finding difficulty (61-68% at baseline and follow-up). Word-finding and focus difficulties were the most commonly reported symptoms. In total, 41% of participants reported some level of depression at baseline and 38% of participants reported depression at one-year follow-up, while 29% and 27% of participants reported some level of anxiety at respective time points.

CONCLUSIONS: Individuals with C19OD are at risk for developing persistent neuropsychiatric conditions. These neurologic and psychiatric sequelae are persistent with repeated longitudinal assessment, even at nearly 2.5 years following initial COVID-19 diagnosis.}, } @article {pmid39766411, year = {2024}, author = {Russo, S and Fiani, F and Napoli, C}, title = {Remote Eye Movement Desensitization and Reprocessing Treatment of Long-COVID- and Post-COVID-Related Traumatic Disorders: An Innovative Approach.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766411}, issn = {2076-3425}, abstract = {Background/Objectives: The COVID-19 pandemic has led to increased mental health issues, particularly among long-COVID patients, who experience persistent symptoms post-recovery, potentially leading to chronic conditions. The psychological impact of long-COVID is still largely unknown, but it may contribute to mental disorders like Post-Traumatic Stress Disorder (PTSD). Given the global rise in anxiety and depression, exploring therapies like Eye Movement Desensitization and Reprocessing (EMDR) for long-COVID traumatic disorders is crucial. This study explores the effectiveness of remote EMDR therapy for PTSD-like symptoms in long-COVID conditions (LCC), assessing their emergence, the impact of LCC on mental health, and identifying key commonalities. It also examines the potential advantages of an artificial intelligence (AI)-powered platform for EMDR treatments for both therapists and patients, evaluating the response differences between remote and in-person treatment. Methods: We enrolled a total of 160 participants divided into two groups of 80, with the experimental group receiving EMDR treatment for PTSD-like symptoms via a remote AI-powered platform, and the control group receiving traditional in-person therapy. We compared the ANOVA for Subjective Units of Disturbance (SUDs) scores, PTSD Checklist for DSM-5 (PCL-5) scores, and Impact of Event Scale-Revised (IES-R) scores between our two groups for three cases: pre-treatment, post-treatment, and decrement. Results: Statistical significance analysis showed a consistent absence of significant differences between online AI-powered platforms and traditional in-presence sessions. This effectively confirms our hypothesis and highlights that no significant differences were observed between the two groups. Conclusions: The AI-supported remote platform demonstrates comparable efficacy in delivering EMDR therapy, confirming its potential as an effective alternative to traditional in-person methods while providing added advantages in accessibility and adaptability (e.g., remote areas, hikikomori, natural disasters).}, } @article {pmid39766408, year = {2024}, author = {Rudroff, T and Klén, R and Rainio, O and Tuulari, J}, title = {The Untapped Potential of Dimension Reduction in Neuroimaging: Artificial Intelligence-Driven Multimodal Analysis of Long COVID Fatigue.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, pmid = {39766408}, issn = {2076-3425}, abstract = {This perspective paper explores the untapped potential of artificial intelligence (AI), particularly machine learning-based dimension reduction techniques in multimodal neuroimaging analysis of Long COVID fatigue. The complexity and high dimensionality of neuroimaging data from modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) pose significant analytical challenges. Deep neural networks and other machine learning approaches offer powerful tools for managing this complexity and extracting meaningful patterns. The paper discusses current challenges in neuroimaging data analysis, reviews state-of-the-art AI approaches for dimension reduction and multimodal integration, and examines their potential applications in Long COVID research. Key areas of focus include the development of AI-based biomarkers, AI-informed treatment strategies, and personalized medicine approaches. The authors argue that AI-driven multimodal neuroimaging analysis represents a paradigm shift in studying complex brain disorders like Long COVID. While acknowledging technical and ethical challenges, the paper emphasizes the potential of these advanced techniques to uncover new insights into the condition, which might lead to improved diagnostic and therapeutic strategies for those affected by Long COVID fatigue. The broader implications for understanding and treating other complex neurological and psychiatric conditions are also discussed.}, } @article {pmid39766328, year = {2024}, author = {Owens, CD and Pinto, CB and Szarvas, Z and Muranyi, M and da C Pinaffi-Langley, AC and Peterfi, A and Mukli, P and Detwiler, S and Olay, L and Kaposzta, Z and Smith, K and Kirkpatrick, AC and Saleh Velez, F and Tarantini, S and Csiszar, A and Ungvari, ZI and Prodan, CI and Yabluchanskiy, A}, title = {COVID-19 Exacerbates Neurovascular Uncoupling and Contributes to Endothelial Dysfunction in Patients with Mild Cognitive Impairment.}, journal = {Biomolecules}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biom14121621}, pmid = {39766328}, issn = {2218-273X}, support = {R01AG075834/GF/NIH HHS/United States ; R21AG080775/GF/NIH HHS/United States ; 966924, 24CDA1276855, and 24DIVSUP1282484//American Heart Association/ ; RF1AG072295, R01AG068295, K01AG073614, and R03AG070479/AG/NIA NIH HHS/United States ; Merit award numbers CX002578 and CX000340//U.S. Department of Veterans Affairs/ ; R01CA255840)/CA/NCI NIH HHS/United States ; U54GM104938//National Institutes of Health; the Oklahoma Shared Clinical and Translational Resources program/ ; T32AG052363//NIA-funded Geroscience Training Program in Oklahoma/ ; }, mesh = {Humans ; *Cognitive Dysfunction/physiopathology/virology/etiology ; *COVID-19/complications/physiopathology ; Male ; Aged ; Female ; *Neurovascular Coupling ; Cross-Sectional Studies ; SARS-CoV-2 ; Middle Aged ; Endothelium, Vascular/physiopathology/virology ; Spectroscopy, Near-Infrared ; }, abstract = {Mild cognitive impairment (MCI) affects nearly 20% of older adults worldwide, with no targetable interventions for prevention. COVID-19 adversely affects cognition, with >70% of older adults with Long COVID presenting with cognitive complaints. Neurovascular coupling (NVC), an essential mechanism of cognitive function, declines with aging and is further attenuated in neurocognitive disorders. The effect of COVID-19 on NVC responses has yet to be addressed in older adults who are vulnerable to dementia progression. Participants with MCI and a history of COVID-19 (COV+, N = 31) and MCI participants with no history of infection (COV- N = 11) participated in this cross-sectional study to determine if COVID-19 affects cerebrocortical NVC responses and vascular function. Functional near-infrared spectroscopy was used to measure cerebrocortical NVC responses, and endothelial function was assessed via insonation of the brachial artery during a flow-mediated dilation protocol. NVC responses were elicited by the working memory n-back paradigm. NVC in the left dorsolateral prefrontal cortex and endothelial function was decreased in the COV+ group compared to the COV- group. These data provide mechanistic insight into how COVID-19 may exacerbate long-term cognitive sequela seen in older adults, highlighting the urgent need for further research and clinical trials to explore novel therapeutic interventions aimed at preserving/restoring NVC.}, } @article {pmid39766256, year = {2024}, author = {Colonna, G}, title = {Interactomic Analyses and a Reverse Engineering Study Identify Specific Functional Activities of One-to-One Interactions of the S1 Subunit of the SARS-CoV-2 Spike Protein with the Human Proteome.}, journal = {Biomolecules}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/biom14121549}, pmid = {39766256}, issn = {2218-273X}, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; *Proteome/metabolism ; *SARS-CoV-2/metabolism ; COVID-19/virology/metabolism ; Protein Interaction Maps ; Protein Binding ; }, abstract = {The S1 subunit of SARS-CoV-2 Spike is crucial for ACE2 recognition and viral entry into human cells. It has been found in the blood of COVID-19 patients and vaccinated individuals. Using BioGRID, I identified 146 significant human proteins that interact with S1. I then created an interactome model that made it easier to study functional activities. Through a reverse engineering approach, 27 specific one-to-one interactions of S1 with the human proteome were selected. S1 interacts in this manner independently from the biological context in which it operates, be it infection or vaccination. Instead, when it works together with viral proteins, they carry out multiple attacks on single human proteins, showing a different functional engagement. The functional implications and tropism of the virus for human organs/tissues were studied using Cytoscape. The nervous system, liver, blood, and lungs are among the most affected. As a single protein, S1 operates in a complex metabolic landscape which includes 2557 Biological Processes (GO), much more than the 1430 terms controlled when operating in a group. A Data Merging approach shows that the total proteins involved by S1 in the cell are over 60,000 with an average involvement per single biological process of 26.19. However, many human proteins become entangled in over 100 different biological activities each. Clustering analysis showed significant activations of many molecular mechanisms, like those related to hepatitis B infections. This suggests a potential involvement in carcinogenesis, based on a viral strategy that uses the ubiquitin system to impair the tumor suppressor and antiviral functions of TP53, as well as the role of RPS27A in protein turnover and cellular stress responses.}, } @article {pmid39765324, year = {2025}, author = {Chopra, A and Franko, N and Chow, EJ}, title = {Navigating neurologic post-COVID-19 conditions in adults: Management strategies for cognitive dysfunction, headaches and neuropathies.}, journal = {Life sciences}, volume = {}, number = {}, pages = {123374}, doi = {10.1016/j.lfs.2025.123374}, pmid = {39765324}, issn = {1879-0631}, abstract = {This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as "long COVID"), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment ("Brain Fog"), headaches, and neuropathies are specifically reviewed.}, } @article {pmid39764743, year = {2025}, author = {Wu, HS and Pathak, D and Hall, M and Given, CW}, title = {Tracking Survivors With Long COVID: Method, Implementation, and Results of an Observational Study.}, journal = {Research in nursing & health}, volume = {}, number = {}, pages = {}, doi = {10.1002/nur.22437}, pmid = {39764743}, issn = {1098-240X}, support = {//This research was supported by the Blue Cross Blue Shield of Michigan Foundation./ ; }, abstract = {While the coronavirus disease 2019 (COVID-19) pandemic has declined, many survivors continue to suffer debilitating symptoms, such as fatigue, pain, and foggy thoughts. Sustained COVID-19 symptoms, or Long COVID, challenge health care resources and economic recovery. This article describes the methodology, implementation, and results of an observational study investigating how time since diagnosis may affect lingering symptoms among the adult COVID-19 population. The descriptive distribution and overall symptoms experience by individuals' characteristics were examined. Random samples from two patient cohorts (n = 147 in 2020-2021 and n = 137 in 2021-2022) were recruited from a COVID-19 patient registry in mid-Michigan. Samples were drawn from a pool of patients ≥ 3 months following their COVID-19 diagnosis. Overall symptoms experience (number, severity, interference) was self-reported using a comprehensive symptom inventory. The findings showed that 66% of the 2020-2021 cohort and 47% of the 2021-2022 cohort reported ≥ 1 lingering symptom with an average of 11.2 (±3.0) and 8.9 (±3.3) months, respectively, after COVID-19 diagnosis. Females reported significantly more symptoms (p = 0.018), higher symptom severity (p = 0.008) and interference (p = 0.007) compared to males. Compared to patients admitted to emergency departments, outpatients reported significantly lower symptom severity (p = 0.020) and less symptom interference (p = 0.018). Our analyses showed that a moderate proportion (43%) of adults remained symptomatic nearly a year after COVID-19 infection and time since diagnosis did not affect symptom experience in either cohort. Female sex and admission setting are important factors to consider for managing and studying Long COVID.}, } @article {pmid39764180, year = {2024}, author = {Engelmann, P and Reinke, M and Stein, C and Salzmann, S and Löwe, B and Toussaint, A and Shedden-Mora, M}, title = {Psychological factors associated with Long COVID: a systematic review and meta-analysis.}, journal = {EClinicalMedicine}, volume = {74}, number = {}, pages = {102756}, pmid = {39764180}, issn = {2589-5370}, abstract = {BACKGROUND: Despite the immense impact of Long COVID on public health and those affected, its aetiology remains poorly understood. Findings suggest that psychological factors such as depression contribute to symptom persistence alongside pathophysiological mechanisms, but knowledge of their relative importance is limited. This study aimed to synthesise the current evidence on psychological factors potentially associated with Long COVID and condition-relevant outcomes like quality of life.

METHODS: In this systematic review and meta-analysis, MEDLINE, PsycINFO, and the Cochrane Database of Systematic Reviews were searched for peer-reviewed studies published in English from 2019 to January 2, 2024. Studies providing cross-sectional or longitudinal data on the association between at least one psychological variable and the presence of Long COVID (primary outcome) or condition-relevant secondary outcomes (symptom severity, impairment, quality of life, and healthcare utilisation) were included. Psychological constructs with at least five comparisons were pooled as odds ratio (OR) for categorical data and standardised mean difference (SMD) for continuous data in random-effects meta-analyses of cross-sectional studies with control groups. This review is registered with PROSPERO, CRD42023408320.

FINDINGS: 113 studies (n = 312,831 patients with Long COVID) provided data on at least one psychological variable, 63 in cross-sectional group comparisons, 53 in cross-sectional associations, and 18 longitudinal. Most reported findings related to depression and anxiety, and - less frequently - to physical activity, posttraumatic stress disorder, stress, and history of mental illness. Depression (OR 2.35; 95% CI, 1.49-3.70) and anxiety (OR 2.53; 95% CI, 1.76-3.61) were significantly associated with Long COVID and higher in affected patients than controls (depression: SMD 0.88; 95% CI, 0.66-1.11; anxiety: SMD 0.74; 95% CI, 0.50-0.99), while results for physical activity and stress were non-significant. In most prospective studies, the investigated psychological constructs significantly predicted Long COVID.

INTERPRETATION: Evidence suggests depression and anxiety to be co-occurring phenomena and predictive factors of Long COVID. Future studies should prospectively investigate psychological constructs such as emotion regulation or dysfunctional symptom expectations, which are well-known risk factors and therapeutic targets of persistent somatic symptoms in other medical conditions, but are so far understudied in Long COVID.

FUNDING: None.}, } @article {pmid39764167, year = {2024}, author = {Zhao, X and Lv, J and Wu, M and Wu, Q}, title = {Clinical characteristics and risk factors for Mycoplasma pneumoniae pneumonia in children.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1438631}, pmid = {39764167}, issn = {2296-2360}, abstract = {BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common pathogens of community-acquired pneumonia (CAP) in children. Although Mycoplasma pneumoniae pneumonia (MPP) is considered a self-limiting disease, severe MPP (SMPP) occurs in some cases. This study aims to analyze clinical features of MPP and to explore predictive indicators in the early stage of M. pneumoniae infection.

METHODS: We retrospectively enrolled patients with MPP and non-MPP (NMPP) hospitalized to the Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2023 to 2024. A total of 757 children with CAP were divided into MPP group and NMPP group. Patients with MPP included SMPP group and mild MPP (MMPP) group. Demographic and clinical characteristics as well as laboratory and imaging tests were deemed to be baseline data within 24 h after admission. We compared differences between MPP group and NMPP group as well as SMPP group and MMPP group. To exclude the impacts of age and gender, analysis of covariance and Logical regression was used to account for the baseline differences in the probability between MPP group and NMPP group, SMPP group and MMPP group. Logistic regression analysis was used to screen markers as potential early clinical predictors. ROC curves were applied to estimate the diagnostic and predictive value of different indicators for SMPP group.

RESULTS: Among the 757 cases of CAP, 464 cases were MPP group and 226 cases were SMPP group. There were significant differences in hospital stay and fever duration between the MPP and NMPP groups. Compared to NMPP group, MPP group exhibited higher levels of platelet count (PLT), heparin-binding protein (HBP), erythrocyte sedimentation rate (ESR), immunoglobulin G (IgG) (P < 0.05). The levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin (SF), prothrombin time (PT), fibrinogen (Fg), interleukin-5 (IL-5) and Gamma interferon (IFN-γ) were significantly increased in SMPP group compared to MMPP group. PT, Fg, SF, IL-5 and IFN-γ were independent risk factors for SMPP group. Significantly, IL-5 and IFN-γ served as reliable predictive indices of SMPP.

CONCLUSIONS: Notable differences were observed in both clinical characteristics and serum inflammatory markers between the MPP group and the NMPP group, as well as between the SMPP group and the MMPP group. Consequently, PT, Fg, SF, IL-5 and IFN-γ hold the potential to be employed as efficacious predictors for SMPP.}, } @article {pmid39764158, year = {2024}, author = {Liu, VY and Godfrey, M and Dunn, M and Fowler, R and Guthrie, L and Dredge, D and Holmes, S and Johnston, AM and Simoneau, T and Fasano, A and Ericson, D and Yonker, LM}, title = {Diagnostic challenges of long COVID in children: a survey of pediatric health care providers' preferences and practices.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1484941}, pmid = {39764158}, issn = {2296-2360}, abstract = {INTRODUCTION: Given the challenges in diagnosing children with long COVID, we sought to explore diagnostic practices and preferences among clinicians.

METHODS: A ten-question survey assessed pediatric providers' clinical decision making for identifying and evaluating long COVID in children. Of the 120 survey respondents, 84 (70%) were physicians, 31 (26%) nurse practitioners, and 5 (4%) physician assistants.

RESULTS: The most common categories of symptoms identified as raising suspicion for long COVID in children included cardiopulmonary symptoms, selected by 119 (99%) of pediatric providers, and neurocognitive symptoms, selected by 118 (98%) of providers. However, there was more ambiguity on the primary feature of long COVID, with providers selecting a range of key symptoms. Of all physical exam findings, postural orthostatic tachycardia, was most suggestive of long COVID [identified by 49 (41%) of pediatric providers], whereas one-third of providers reported no specific identifiable exam finding.

DISCUSSION: Pediatric providers report variable decision making in the clinical evaluation of long COVID, with patient demographics and clinical factors impacting whether a diagnosis of long COVID is considered. This variation in diagnosing pediatric long COVID reflects ambiguity in the definition of long COVID in children and the absence of clinical guidelines to support providers in the identification of disease and treatment. This study highlights an area of need for future clinical advances in pediatric long COVID.}, } @article {pmid39763676, year = {2024}, author = {Maciel, ABS and Pinto, AS and Maia Silva, B and Goulart, CL and Silva, LFA and Chaves, AS and Mouta, GS and Sato, CMS and Valente, J and Mwangi, VI and de Melo, GC and Monteiro, W and Lacerda, M and Arêas, GPT and Sampaio, VS and Costa, AG and Almeida-Val, F}, title = {Inflammatory discoveries two years after acute severe COVID-19: a longitudinal biomarker profile assessment in long COVID individuals in the Brazilian Amazon.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1520193}, pmid = {39763676}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/blood ; Male ; *Biomarkers/blood ; Female ; Brazil/epidemiology ; Middle Aged ; *Cytokines/blood ; *SARS-CoV-2/immunology ; Adult ; Inflammation/blood/immunology ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines/immunology ; Aged ; Fatigue/blood ; }, abstract = {BACKGROUND: In SARS-CoV-2 infection, cytokines and laboratory biomarkers play a key role in disease progression and their long-term levels have been associated with the outcome of long COVID-19.

OBJECTIVES: I) study the levels of cytokines, hematological and biochemical biomarkers in the acute and post-acute phases of COVID-19 disease; and II) assess the impact of COVID-19 vaccine doses on fatigue symptoms.

METHODS: This study is an exploratory cohort nested within a clinical and laboratory follow-up of surviving participants after pre-vaccine acute COVID-19 infection with severe clinical manifestations. We analyzed the inflammatory biomarker profiles of fifty SARS-Cov-2 negative healthy controls from before the COVID-19 pandemic, and eighty patients in the acute phase (Day 1, Day 7 and Day 14), and during 4 months and 2 years after hospitalization.

RESULTS: Four months after hospitalization, 91.3% (73/80) of patients exhibited onset of long COVID symptoms, which persisted in 63.7% (51/80) after 2 years. Comparing the baseline values of the cytokines in the controls versus the follow-up times, the cytokines IL-6, IL-8 and IL-10 were high in the acute phase, declining over time after the individual's recovery, while IL-1β showed an inverse variation, remaining high after 2 years. IL-1β, IL-10, and TNF increased over time post-acute infection, indicating a long-term inflammatory response. Vaccination with four doses, compared to three doses, showed a slight protective effect against fatigue symptoms in the male population (IRR 0.48, 95% CI 0.22 - 1.02; p=0.054). Neutrophil and leukocyte counts showed a significant reduction 2 years after hospitalization. However, platelet count was the laboratory biomarker that best reflects the prediction of long COVID symptoms up for to 2 years.

CONCLUSION: Although the frequency of long COVID symptoms declines over time after the acute illness, symptoms continue to persist 2 years after hospital discharge. Vaccination with a fourth dose booster appears to significantly influence reduction of symptoms associated with long COVID fatigue among the males. We further identified important laboratory biomarkers for long COVID. Elevated levels of IL-1β, IL-10, and TNF, along with low levels of IL-6, IL-18, and IL-12p70, also offer new insights into the inflammatory state in long COVID.}, } @article {pmid39763550, year = {2024}, author = {Worden, L and Wannier, R and Archer, H and Blumberg, S and Kwan, A and Sears, D and Porco, TC}, title = {COVID-19 Reproduction Numbers and Long COVID Prevalences in California State Prisons.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.14.24319022}, pmid = {39763550}, abstract = {Prisons have been hotspots for COVID-19 and likely an important driver of racial disparity in disease burden. From the first COVID-19 case detected through March 25, 2022, 66,684 of 196,652 residents of California's state prison system were infected, most of them in two large winter waves of outbreaks that reached all 35 of the state prisons. We used individual-level data on disease timing and nightly room assignments in these prisons to reconstruct locations and pathways of transmission statistically, and from that estimated reproduction numbers, locations of unobserved infection events, and the subsequent magnitude and distribution of long COVID prevalence. Where earlier work has recommended smaller cells over large dormitory housing to reduce transmission, recommended use of cells with solid doors over those with bars only, and cautioned against reliance on solid doors (e.g., in cold months when HVAC systems can circulate aerosols), we found evidence of substantial transmission in both dorms and cells regardless of the door and season. Effective reproduction numbers were found to range largely between 0 and 5, in both cells and dorms of all door types. Our estimates of excess case rates suggest that as a result of disparities in incarceration, prison outbreaks contributed to disproportionate disease burden on Black and Indigenous people in California. We estimated that 9,100-11,000 people have developed long COVID as a result of infection in these prison outbreaks, 1,700-2,000 of them with disabling consequences, and that this burden is disproportionately on Black and Indigenous people in comparison to the state as a whole. We urge high-quality medical care for prison residents affected by long COVID, and decarceration to reduce the risk of future outbreaks of both COVID-19 and other diseases.}, } @article {pmid39763475, year = {2025}, author = {Magalhães, BK and Silva, VPS and Machado, MN and Nakazone, MA}, title = {Prognostic value of Chagas heart disease on short- and long-term clinical outcomes in patients hospitalized for COVID-19.}, journal = {Transactions of the Royal Society of Tropical Medicine and Hygiene}, volume = {}, number = {}, pages = {}, doi = {10.1093/trstmh/trae141}, pmid = {39763475}, issn = {1878-3503}, support = {#2022/06733-9//FAPESP/ ; #121755/2022-3//CNPq/ ; }, abstract = {BACKGROUND: Immunological similarities led us to explore potential interactions between Chagas heart disease (CHD) and coronavirus disease 2019 (COVID-19). We evaluated CHD's impact on the short- and long-term clinical courses of COVID-19 patients.

METHODS: The CHD group comprised consecutive hospitalized patients (March 2020-March 2022), while the controls were selected through genetic matching based on COVID complications predictors. Cox proportional hazards models were used to assess the predictive value of CHD.

RESULTS: Among 114 patients (50.9% male, 82.5% Caucasian, median age 66 y), prevalent comorbidities included cardiovascular diseases (84.2%) and type 2 diabetes (15.8%). Over a 22-month follow-up, no significant difference in the composite outcome (death and decompensated heart failure) was found between CHD patients (68.4%) and controls (72.6%, p=0.709). In-hospital and post-discharge clinical courses showed similarities in presentation, exams, respiratory support, long-COVID manifestations and death (p>0.05). Cox models identified age (every 10 y) (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.31 to 2.20], p<0.001) and normal lymphocyte count (800-1600/mm3) (HR 0.94 [95% CI 0.89 to 0.98], p=0.007) as independent predictors of mortality.

CONCLUSIONS: CHD does not significantly impact clinical presentation, in-hospital outcomes or long-COVID manifestations. Age and lymphocyte count are independent predictors of mortality, emphasizing their prognostic significance in COVID-19 complications, regardless of comorbidities.}, } @article {pmid39763448, year = {2025}, author = {Gonzalez-Ochoa, AJ and Szolnoky, G and Hernandez-Ibarra, AG and Fareed, J}, title = {Treatment with Sulodexide Downregulates Biomarkers for Endothelial Dysfunction in Convalescent COVID-19 Patients.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {31}, number = {}, pages = {10760296241297647}, pmid = {39763448}, issn = {1938-2723}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Biomarkers/blood ; C-Reactive Protein/metabolism/analysis ; Convalescence ; *COVID-19/blood/complications ; *COVID-19 Drug Treatment ; Double-Blind Method ; Down-Regulation ; *Endothelium, Vascular/drug effects ; Fibrin Fibrinogen Degradation Products/analysis/metabolism ; *Glycosaminoglycans/therapeutic use ; Interleukin-6/blood ; Mexico ; *Thrombomodulin/blood ; }, abstract = {INTRODUCTION: Persistent elevation of biomarkers associated with endothelial dysfunction in convalescent COVID-19 patients has been linked to an increased risk of long-term cardiovascular complications, including long COVID syndrome. Sulodexide, known for its vascular endothelial affinity, has demonstrated pleiotropic protective properties. This study aims to evaluate the impact of sulodexide on serum levels of endothelial dysfunction biomarkers in patients during the convalescent phase of COVID-19.

METHODS: We conducted a double-blind, single-center, randomized, placebo-controlled trial in Mexico, comparing sulodexide (250 LRU orally, twice daily) with placebo over 8 weeks in adult patients during early COVID-19 convalescence. Differences in serum biomarkers between the groups were analyzed using repeated measures and post hoc tests, with Thrombomodulin (TM) as the primary endpoint.

RESULTS: Among 206 analyzed patients (103 in each group), at week 8, the sulodexide group exhibited significantly lower mean levels of Thrombomodulin (TM) (25.2 ± 7.9 ng/mL vs 29.9 ± 14.7 ng/mL, P = .03), von Willebrand Factor (vWF) (232 ± 131 U/dL vs 266 ± 122 U/dL, P = .02) and Interleukin-6 (IL-6) (12.5 ± 13.2 pg/mL vs 16.2 ± 16.5 pg/mL, P = .03) compared to the placebo group. D-dimer and C reactive protein (CRP) in the sulodexide group were also lowered. No significant differences were observed for P-selectin, fibrinogen, VCAM-1, or ICAM-1 levels.

CONCLUSIONS: Patients in the convalescent phase of COVID-19 who received sulodexide for eight weeks showed a reduction in TM, vWF, D-dimer, CRP, and IL-6 serum levels compared to placebo. These findings suggest a potential protective effect of sulodexide against thromboinflammation and endothelial damage.}, } @article {pmid39762934, year = {2024}, author = {Seo, JW and Song, JY}, title = {Reply: How Can Chronic COVID (Long-COVID Syndrome) Be Diagnosed and Treated?.}, journal = {Infection & chemotherapy}, volume = {56}, number = {4}, pages = {561-563}, pmid = {39762934}, issn = {2093-2340}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, } @article {pmid39762933, year = {2024}, author = {Finsterer, J}, title = {How Can Chronic COVID (Long-COVID Syndrome) Be Diagnosed and Treated?.}, journal = {Infection & chemotherapy}, volume = {56}, number = {4}, pages = {559-560}, pmid = {39762933}, issn = {2093-2340}, } @article {pmid39762640, year = {2025}, author = {Cohen, AK and Jaudon, TW and Schurman, EM and Kava, L and Vogel, JM and Haas-Godsil, J and Lewis, D and Crausman, S and Leslie, K and Bligh, SC and Lizars, G and Davids, JD and Sran, S and Peluso, M and McCorkell, L}, title = {Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {261}, pmid = {39762640}, issn = {2730-664X}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir.

METHODS: We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.5-30 days) of oral nirmatrelvir/ritonavir outside (n = 11) of and within (n = 2) the context of an acute SARS-CoV-2 infection. Participants reported on symptoms and health experiences before, during, and after their use of nirmatrelvir/ritonavir.

RESULTS: Among those who take an extended course of nirmatrelvir/ritonavir outside of the context of an acute infection, some experience a meaningful reduction in symptoms, although not all benefits persist. Others experience no effect on symptoms. One participant stopped early due to intense stomach pain. For the two participants who took an extended course of nirmatrelvir/ritonavir within the context of an acute reinfection, both report eventually returning to their pre-re-infection baseline.

CONCLUSIONS: Extended courses of nirmatrelvir/ritonavir may have meaningful benefits for some people with Long COVID but not others. We encourage researchers to study how and why nirmatrelvir/ritonavir benefits some and what course length is most effective, with the goal of informing clinical recommendations for using nirmatrelvir/ritonavir and/or other antivirals as a potential treatment for Long COVID.}, } @article {pmid39762108, year = {2025}, author = {Al-Oraibi, A and Martin, CA and Woolf, K and Bryant, L and Nellums, LB and Tarrant, C and Khunti, K and Pareek, M}, title = {Prevalence of and factors associated with long COVID among diverse healthcare workers in the UK: a cross-sectional analysis of a nationwide study (UK-REACH).}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e086578}, doi = {10.1136/bmjopen-2024-086578}, pmid = {39762108}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Ethnicity/statistics & numerical data ; *Health Personnel/statistics & numerical data ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prevalence ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: To assess the prevalence of UK healthcare workers (HCWs) who reported symptoms of COVID-19 lasting for longer than 5 weeks and examine associated factors with experiencing long COVID in an ethnically diverse cohort.

DESIGN: A cross-sectional study using data from the UK Research study into Ethnicity And COVID-19 Outcomes in HCWs cohort study.

SETTING: Data were collected electronically between December 2020 and March 2021.

PARTICIPANTS: Individuals aged 16 years or older, residing in the UK, and working as HCWs or ancillary workers in a healthcare setting and/or registered with one of the seven major UK healthcare professional regulators.

The main outcome was long COVID (symptoms>5 weeks). The primary exposure of interest was self-reported ethnicity. We employed univariable and multivariable logistic regression to identify associations. We adjusted for demographic information, health status and existing long-term conditions in our multivariate analysis.

RESULTS: In our analysis of 11 513 HCWs, we found that 2331 (20.25%) reported COVID-19, of whom 525 (22.52%) experienced long COVID. There were no significant differences in risk of long COVID by ethnic group. In terms of other demographic characteristics, the majority of those experiencing long COVID were female (80.0%) and were slightly older than those who did not experience long COVID (median age 46 (IQR 36-54)). In multivariable analyses of those who reported having had COVID-19, HCWs in nursing/midwifery roles (adjusted OR (aOR) 1.76, 95% CI 1.26 to 2.46; p=0.001) and allied health professions (aOR 1.42, 95% CI 1.05 to 1.93; p=0.023) had higher odds of experiencing long COVID compared with those in medical roles. Other factors significantly associated with long COVID included self-reported psychological conditions (eg, depression and anxiety) and respiratory conditions (eg, asthma).

CONCLUSIONS: In this large ethnically diverse cohort study, more than one in five UK HCWs reported experiencing long COVID after acute COVID-19 during the first year of the pandemic. We found that specific demographic (older age and female gender) and occupational factors (nursing/midwifery and allied health professions) were associated with higher odds of long COVID. Notably, there were no significant differences in the risk of long COVID by ethnic group. Further research and collaborative efforts are urgently needed to address these factors effectively, develop targeted interventions and understand the temporal and longitudinal dynamics of the condition.}, } @article {pmid39762090, year = {2025}, author = {Honchar, O and Ashcheulova, T and Chumachenko, T and Chumachenko, D}, title = {Early prediction of long COVID-19 syndrome persistence at 12 months after hospitalisation: a prospective observational study from Ukraine.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e084311}, doi = {10.1136/bmjopen-2024-084311}, pmid = {39762090}, issn = {2044-6055}, mesh = {Humans ; Female ; Male ; Prospective Studies ; *COVID-19/epidemiology/complications ; Middle Aged ; *Hospitalization ; Ukraine/epidemiology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cross-Sectional Studies ; Prognosis ; Aged ; Self Report ; }, abstract = {OBJECTIVE: To identify the early predictors of a self-reported persistence of long COVID syndrome (LCS) at 12 months after hospitalisation and to propose the prognostic model of its development.

DESIGN: A combined cross-sectional and prospective observational study.

SETTING: A tertiary care hospital.

PARTICIPANTS: 221 patients hospitalised for COVID-19 who have undergone comprehensive clinical, sonographic and survey-based evaluation predischarge and at 1 month with subsequent 12-month follow-up. The final cohort included 166 patients who had completed the final visit at 12 months.

MAIN OUTCOME MEASURE: A self-reported persistence of LCS at 12 months after discharge.

RESULTS: Self-reported LCS was detected in 76% of participants at 3 months and in 43% at 12 months after discharge. Patients who reported incomplete recovery at 1 year were characterised by a higher burden of comorbidities (Charlson index of 0.69±0.96 vs 0.31±0.51, p=0.001) and residual pulmonary consolidations (1.56±1.78 vs 0.98±1.56, p=0.034), worse blood pressure (BP) control (systolic BP of 138.1±16.2 vs 132.2±15.8 mm Hg, p=0.041), renal (estimated glomerular filtration rate of 59.5±14.7 vs 69.8±20.7 mL/min/1.73 m[2], p=0.007) and endothelial function (flow-mediated dilation of the brachial artery of 10.4±5.4 vs 12.4±5.6%, p=0.048), higher in-hospital levels of liver enzymes (alanine aminotransferase (ALT) of 76.3±60.8 vs 46.3±25.3 IU/L, p=0.002) and erythrocyte sedimentation rate (ESR) (34.3±12.1 vs 28.3±12.6 mm/h, p=0.008), slightly higher indices of ventricular longitudinal function (left ventricular (LV) global longitudinal strain (GLS) of 18.0±2.4 vs 17.0±2.3%, p=0011) and higher levels of Hospital Anxiety and Depression Scale anxiety (7.3±4.2 vs 5.6±3.8, p=0.011) and depression scores (6.4±3.9 vs 4.9±4.3, p=0.022) and EFTER-COVID study physical symptoms score (12.3±3.8 vs 9.2±4.2, p<0.001). At 1 month postdischarge, the persisting differences included marginally higher LV GLS, mitral E/e' ratio and significantly higher levels of both resting and exertional physical symptoms versus patients who reported complete recovery. Logistic regression and machine learning-based binary classification models have been developed to predict the persistence of LCS symptoms at 12 months after discharge.

CONCLUSIONS: Compared with post-COVID-19 patients who have completely recovered by 12 months after hospital discharge, those who have subsequently developed 'very long' COVID were characterised by a variety of more pronounced residual predischarge abnormalities that had mostly subsided by 1 month, except for steady differences in the physical symptoms levels. A simple artificial neural networks-based binary classification model using peak ESR, creatinine, ALT and weight loss during the acute phase, predischarge 6-minute walk distance and complex survey-based symptoms assessment as inputs has shown a 92% accuracy with an area under receiver-operator characteristic curve 0.931 in prediction of LCS symptoms persistence at 12 months.}, } @article {pmid39760348, year = {2025}, author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D}, title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part II.}, journal = {Pediatric annals}, volume = {54}, number = {1}, pages = {e40-e44}, doi = {10.3928/19382359-20241106-01}, pmid = {39760348}, issn = {1938-2359}, mesh = {Humans ; *COVID-19/complications ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems-neurology, psychiatry, endocrinology, hematology, and oncology-under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [Pediatr Ann. 2025;54(1):e40-e44.].}, } @article {pmid39755001, year = {2025}, author = {Lukanov, T and Mihaylova, A and Al Hadra, B and Lesichkova, S and Georgieva, A and Popov, T and Krasteva, Y and Mondeshki, T and Naumova, E}, title = {HLA-DQB1*05:03 is associated with an increased risk of COVID-19 progression in the Bulgarian population.}, journal = {Human immunology}, volume = {86}, number = {1}, pages = {111228}, doi = {10.1016/j.humimm.2024.111228}, pmid = {39755001}, issn = {1879-1166}, abstract = {The SARS-CoV-2 outbreak represents a global health problem. The different infection rates are heavily influenced by host genetic factors, such as variability in the HLA region. The aim of our study was to investigate whether certain HLA alleles in the Bulgarian population contribute to COVID-19 progression and their role in anti-SARS-CoV-2 immunity. We evaluated 76 patients diagnosed with COVID-19 and classified them according to severity as mild, moderate, and severe. Data from a population cohort (n = 539), representative of the Bulgarian population, was used for comparisons. We found that the HLA-DQB1*05:03 (OR = 3.13, pc = 0.0008) allele was significantly associated with COVID-19 severity. Several other class I and class II alleles showed a promising association with a predisposition to disease severity or a protective role in its progression. This is the first study to assess the association between HLA and COVID-19 progression in the Bulgarian population. Despite some limitations, our results suggest that certain HLA alleles play a role in the severity of SARS-CoV-2 infection and it would be interesting to further trace their effect in the context of long COVID.}, } @article {pmid39754403, year = {2025}, author = {Nawa, H and Murakami, M}, title = {Neurobiology of COVID-19-Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling.}, journal = {Neuropsychopharmacology reports}, volume = {45}, number = {1}, pages = {e12520}, pmid = {39754403}, issn = {2574-173X}, support = {//Grant for Joint Research Program of the Institute for Genetic Medicine, Hokkaido University/ ; 21K18242//Grant-in-Aid for Challenging Exploratory Research/ ; 22H02728//Grant-in-Aid for Scientific Research (B)/ ; JP20fk0108471//AMED/ ; JP21fk0108489//AMED/ ; JP22ek0510030h0003//AMED/ ; JP223fa627005h0001//AMED/ ; JP20ek0510030h0001//AMED/ ; JP19ek0210125h0001//AMED/ ; JP21zf0127004h0001//AMED/ ; JP20H00502//Scientific Research (A)/ ; JP21K19364//Challenging Exploratory Research/ ; JPMXS0120330644//MEXT Quantum LEAP Flagship Program/ ; JP20fk010847h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; JP21fk0108489h0001//Research Program on Emerging and Re-emerging Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/complications/metabolism ; *ErbB Receptors/metabolism ; *Schizophrenia/metabolism/physiopathology/drug therapy ; Animals ; *Signal Transduction ; *Psychotic Disorders/metabolism/physiopathology/etiology/drug therapy ; SARS-CoV-2 ; Brain/metabolism/virology ; }, abstract = {COVID-19 exhibits not only respiratory symptoms but also neurological/psychiatric symptoms rarely including delirium/psychosis. Pathological studies on COVID-19 provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role in the progression of viral replication and lung fibrosis. Of note, SARS-CoV-2 virus (specifically, S1 spike domain) mimics EGF and directly transactivates EGFR, preceding the inflammatory process. In agreement, the anticancer drugs targeting EGFR such as Nimotuzumab and tyrosine kinase inhibitors are markedly effective on COVID-19. However, these data might raise a provisional caution regarding implication of psychiatric disorder such as schizophrenia. The author's group has been investigating the etiologic and neuropathologic associations of EGFR signaling with schizophrenia. There are significant molecular associations between schizophrenia and EGFR ligand levels in blood as well as in the brain. In addition, perinatal challenges of EGFR ligands and intraventricular administration of EGF to rodents and monkeys both resulted in severe behavioral and/or electroencephalographic endophenotypes relevant to this disorder. These animal models also display postpubertal abnormality in soliloquy-like self-vocalization as well as in intercortical functional connectivity. Here, we discuss neuropsychiatric implication of coronavirus infection and its interaction with the EGFR system, by searching related literatures in PubMed database as of the end of 2023.}, } @article {pmid39752161, year = {2025}, author = {Rytz, CL and King, JA and Saad, N and Ronksley, PE and Somayaji, R and Raj, SR and Dumanski, SM and Newbert, AM and Peace, LD and Ahmed, SB}, title = {Validating a Case Definition for Transgender Adults Using Administrative Data.}, journal = {JAMA network open}, volume = {8}, number = {1}, pages = {e2451700}, pmid = {39752161}, issn = {2574-3805}, mesh = {Humans ; *Transgender Persons/statistics & numerical data ; Male ; Female ; Adult ; Cohort Studies ; Middle Aged ; Alberta ; Self Report ; Young Adult ; Gender Identity ; }, abstract = {IMPORTANCE: Administrative health data serve as promising data sources to study transgender health at a population level in the absence of self-reported gender identity.

OBJECTIVE: To develop and validate case definitions identifying transgender adults in administrative data compared with the reference standard of self-reported gender identity in a universal health care setting.

In this cohort study conducted in Alberta, Canada, data from provincial administrative health data sources including inpatient hospitalizations, emergency department encounters, primary care visits, prescription drug dispensations, and the provincial health insurance registry were linked and used to develop 15 case definitions (9 for transgender women and 6 for transgender men). Participants aged 18 years or older with a provincial health care number between April 1, 1994, and March 31, 2021, were included and stratified by sex marker (eg, female or male) at study entry. Data analysis was from December 2023 to March 2024.

MAIN OUTCOMES AND MEASURES: For each case definition, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated against the reference standard of self-reported gender identity.

RESULTS: In this cohort study of 5 375 735 individuals, the reference standard consisted of 141 self-identified transgender women, 174 self-identified transgender men, 111 self-identified cisgender women, and 65 self-identified cisgender men. The final cohort representing transgender women participants who met at least 1 case definition and/or were part of the standard reference totaled 63 977. Combining a case definition employing male sex registry identification and 2 or more dispensations of estrogen or a case definition employing male sex registry identification and at least 1 gender-related diagnostic code demonstrated a sensitivity of 86.6% (95% CI, 79.9%-91.7%), specificity of 62.5% (95% CI, 51.5%-72.6%), PPV of 78.8% (95% CI, 71.6%-85.0%), and NPV of 74.3% (95% CI, 62.8%-83.8%). The final cohort representing transgender men participants who met at least 1 case definition and/or were part of the standard reference totaled 26 852. Combining a case definition employing female sex registry identification and 2 or more dispensations of testosterone or a case definition employing female sex registry identification and at least 1 gender-related diagnostic code demonstrated a sensitivity of 78.2% (95% CI, 71.3%-84.1%), specificity of 89.2% (95% CI, 82.2%-94.1%), PPV of 91.3% (95% CI, 85.5%-95.3%), and NPV of 73.8% (95% CI, 65.8%-80.7%).

CONCLUSION AND RELEVANCE: These findings suggest that case definitions using transgender-related diagnostic codes and gender-affirming hormone prescriptions can be used to study the epidemiology, disease burden, and health care utilization of transgender populations.}, } @article {pmid39750036, year = {2025}, author = {Mazer, B and Feldman, DE}, title = {Demographic and clinical factors associated with functional changes in Long-Covid.}, journal = {American journal of physical medicine & rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1097/PHM.0000000000002686}, pmid = {39750036}, issn = {1537-7385}, abstract = {Many people experience symptoms months or years following COVID-19 infection. The impact of these symptoms on daily functioning and factors associated with functional decline are not well understood. This study aimed to describe functional changes among persons with Long-Covid and explore associated sociodemographic and clinical factors. 2764 adults who tested positive for COVID-19 were recruited at >12 weeks after diagnosis. Participants responded to an electronic survey [Newcastle Post-COVID Syndrome Questionnaire (symptoms); COVID-19 Yorkshire Rehabilitation Screen (activities; perceived global health, mobility, personal care, daily activities)]. 37.8% were classified as having Long-Covid based on the positive response to "Are you still troubled by symptoms?". The majority of them reported a decline in global health, mobility, and participation in daily activities. Common changes in function included fatigue, breathlessness upon climbing stairs and when dressing, decline in participation in usual activities, anxiety, pain/discomfort, and reduced concentration. Having COVID-19 > 1 year prior was associated with change in perceived global health (OR = 1.5). Being infected >12 months prior (OR = 1.5), hospitalized for COVID-19 (OR = 2.2-2.4), >1 chronic comorbid conditions (OR = 1.6), and obesity (OR = 1.6) were associated with functional decline. Many of those infected with COVID-19 experience long-lasting symptoms impacting daily functioning. Multidisciplinary medical and rehabilitation services are needed to help improve recovery and maximize functioning.}, } @article {pmid39747636, year = {2025}, author = {Wirtz, AL and Reisner, SL and Cole, SW and Adams, D and Davids, JD and Cohen, AK and Brown, C and Miller, M and Poteat, TC}, title = {Long COVID in transgender and gender nonbinary people in the United States.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {383}, pmid = {39747636}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; United States/epidemiology ; *Transgender Persons/statistics & numerical data ; Adult ; Cross-Sectional Studies ; Middle Aged ; Young Adult ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; Adolescent ; Prevalence ; Gender Identity ; Aged ; Sexual and Gender Minorities/statistics & numerical data ; }, abstract = {Despite recommendations in the US National Research Action Plan on Long COVID, gender identity is rarely reported in research and surveillance used to guide public health programming and clinical care. We analyzed data from a cross-sectional study of COVID-19 in a nationwide sample of transgender and nonbinary (TNB) people (N = 2,134). Participants were surveyed between June 14, 2021 and May 1, 2022. Data were restricted to 817 participants who reported confirmed or suspected COVID-19 to estimate the prevalence of long COVID, defined as symptoms persisting for ≥ 3 months. Ten percent of participants with a history of COVID-19 reported symptom duration consistent with long COVID, ranging from 4.8% to 12.9% across gender identities. Long COVID was most common in transmasculine and nonbinary people assigned female sex at birth. There was no evidence of an association with reported hormone therapy, supporting current recommendations that prioritize gender-affirming care during treatment for long COVID. As a condition which profoundly impacts health and productivity, long COVID is likely to exacerbate existing disparities. Principles of equity demand that we reduce barriers to prevention, diagnosis, and care for long COVID, and ensure that research and surveillance are inclusive of TNB people and disaggregate findings by gender identity.}, } @article {pmid39747631, year = {2025}, author = {Zhang, D and Chen, C and Xie, Y and Zhou, S and Li, D and Zeng, F and Huang, S and Lv, Y and Huang, X and Mao, F and Kuang, J and Gan, J and Xu, X and Chen, S and Chen, R and Zhang, X and Xu, S and Zeng, M and Ren, H and Bai, F}, title = {Prevalence and risk factors of long COVID-19 persisting for 2 years in Hainan Province: a population-based prospective study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {369}, pmid = {39747631}, issn = {2045-2322}, support = {Qhyb2022-133//Hainan Provincial Postgraduate Innovation Research Project/ ; hnjg2024-67//Hainan Province Education Reform Project/ ; hnjg2024-67//Hainan Province Education Reform Project/ ; YSPTZX202313//The specific research fund of The Innovation Platform for Academicians of Hainan Province/ ; 202330//National Clinical Key Speciality Capacity Building Project/ ; WSJK2024MS150//Joint Project on Health Science and Technology Innovation in Hainan Province/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; China/epidemiology ; Male ; Female ; Middle Aged ; Risk Factors ; Prevalence ; Aged ; Adult ; Prospective Studies ; *SARS-CoV-2/isolation & purification ; Fatigue/epidemiology ; Young Adult ; Cough/epidemiology ; Dizziness/epidemiology ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to persistent symptoms, sequelae, and other medical complications that may last for weeks or months after recovery. The aim of the study is to assess the prevalence and risk factors of long COVID-19 persisting for 2 years in Hainan Province, China, to aid in its recognition, prevention, and treatment. Between July and August 2022, 960 individuals with confirmed SARS-CoV-2 infection in Hainan, China, were recruited. An epidemiological questionnaire was conducted via phone interviews to assess participants' recovery status after 2 years. Among the participants, 120 patients (12.5%) experienced at least one long COVID-19 complication. The most common symptoms were cough (33.3%, 40/120), followed by fatigue (25.9%, 31/120), hair loss (23.3%, 28/120), and dizziness (20.8%, 25/120). Independent risk factors included age over 65, moderate to severe infection, chronic diseases, irregular diet, late sleeping, anxiety, and fewer than 2 vaccinations (p < 0.05). While most individuals infected with COVID-19 fully recover, approximately 12.5% experience intermediate or long-term effects. This study is the first to identify the incidence and associated risk factors of long COVID-19 with the longest follow-up time, providing valuable insights for the timely restoration of pre-COVID-19 health.}, } @article {pmid39745850, year = {2025}, author = {Clark, PA and Horn, S and Wang, N and Lyketsos, CG and Parker, AM and Oh, ES and Vannorsdall, TD}, title = {Rates and Predictors of Performance Validity Test Failure in Adults Treated for Post-COVID-19 Condition: a Brief Report.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {}, number = {}, pages = {}, doi = {10.1093/arclin/acae122}, pmid = {39745850}, issn = {1873-5843}, support = {P30AG066507//Johns Hopkins Alzheimer's Disease Research Center/ ; R01AG057725/NH/NIH HHS/United States ; }, abstract = {>OBJECTIVE: Cognitive dysfunction is a common symptom of post-COVID-19 condition (PCC). Few studies have examined rates and predictors of cognitive performance validity test (PVT) failure in patients seeking treatment for PCC.

>METHODS: We report the rates of PVT failure in 323 patients who received care in a long-COVID-19 clinic for any post-COVID-19 health concern and underwent routine telephone cognitive testing that included two embedded PVTs. Binary logistic regressions examined the demographic, illness, and psychological variables associated with PVT failure.

>RESULTS: The prevalence of single PVT failure ranged from 4.7% to 26.1% whereas failure on both PVTs occurred in just 6.3%. Illness characteristics, subjective cognitive dysfunction, and most demographic and psychological variables were unrelated to single PVT failure. Males and those with anxiety were more likely to fail both PVTs.

>CONCLUSION: Failure across multiple PVTs was not common and was unrelated to COVID-19 severity or cognitive complaints.}, } @article {pmid39744674, year = {2024}, author = {Menezes, F and Palmeira, JDF and Oliveira, JDS and Argañaraz, GA and Soares, CRJ and Nóbrega, OT and Ribeiro, BM and Argañaraz, ER}, title = {Unraveling the SARS-CoV-2 spike protein long-term effect on neuro-PASC.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1481963}, pmid = {39744674}, issn = {1662-5102}, abstract = {The persistence or emergence of long-term symptoms following resolution of primary SARS-CoV-2 infection is referred to as long COVID or post-acute sequelae of COVID-19 (PASC). PASC predominantly affects the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Among these, the central nervous system (CNS) is significantly impacted, leading to a spectrum of symptoms, including fatigue, headaches, brain fog, cognitive impairment, anosmia, hypogeusia, neuropsychiatric symptoms, and peripheral neuropathy (neuro-PASC). However, the risk factors and pathogenic mechanisms responsible for neuro-PASC remain unclear. This review hypothesis discusses the leading hypotheses regarding the pathophysiological mechanisms involved in long COVID/PASC, focusing on neuro-PASC. We propose vascular dysfunction mediated by activation of astrocytes and pericytes followed by blood-brain barrier (BBB) disruption as underlying pathophysiological mechanisms of neurological manifestations. Additionally, we provide insights into the role of spike protein at the blood-brain interface. Finally, we explore the potential pathogenic mechanisms initiated by the interaction between the spike protein and cellular receptors at the brain endothelial and tissue levels.}, } @article {pmid39744372, year = {2024}, author = {Miranda, ALDC and Costa, VLDS and da Paixão, ART and Martins, MB and Polaro, SHI and Cunha, CLF and Botelho, EP and Pedroso, AO and Silva, ACOE and Reis, RK and Ferreira, GRON}, title = {Factors associated with access to health services among people with long COVID in the Brazilian Amazon.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1503907}, pmid = {39744372}, issn = {2296-2565}, mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology ; Cross-Sectional Studies ; *Health Services Accessibility/statistics & numerical data ; Female ; Male ; Middle Aged ; Adult ; Surveys and Questionnaires ; Aged ; SARS-CoV-2 ; Young Adult ; Adolescent ; Logistic Models ; }, abstract = {BACKGROUND: Access to healthcare services for the population with long COVID is a challenge, as healthcare systems have been tasked with responding effectively to the extensive clinical heterogeneity of this disease.

OBJECTIVE: To analyze the factors associated with access to health services among people with long COVID in the Brazilian Amazon.

METHODS: This is a cross-sectional study using a quantitative method, conducted through an online survey between May 2023 and January 2024. The study included participants aged 18 years or older, residing in the northern region of Brazil, with a confirmed diagnosis of COVID-19 and who experienced long COVID. Participants completed an adapted version of the questionnaire on the Research Electronic Data Capture platform. Data were analyzed by multiple logistic regression.

RESULTS: A total of 364 people with long COVID participated in the study, of which only 167 (45.88%) had access to healthcare to treat the symptoms of this clinical condition. In the final multiple logistic regression model, only factors related to the need for services were associated with healthcare access. Participants with symptoms of dermatological alterations (AOR = 2.57; p = 0.01), a pre-COVID-19 diagnosis of chronic disease (AOR = 5.62; p = 0.04), those who treated their most severe COVID-19 infection with the assistance of a healthcare professional (AOR = 4.97; p = 0.01), and those who used antibiotics during their most severe COVID-19 infection (AOR = 3.24; p = 0.01) were more likely to access healthcare services for treating long COVID.

CONCLUSION: Factors related to the need for services were the only ones associated in this population. It is important to know these aspects to identify the most affected populations and propose measures.}, } @article {pmid39741599, year = {2024}, author = {Kakavand, B and Centner, S and Centner, A}, title = {Association Between COVID-19 and Orthostatic Intolerance in Children: A Retrospective Study.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e74857}, pmid = {39741599}, issn = {2168-8184}, abstract = {Introduction SARS-CoV-2 infection (COVID-19) and the COVID-19 vaccine have been linked to the development of persistent symptoms, including orthostatic intolerance (OI) and postural orthostatic tachycardia syndrome (POTS), in both children and adults. POTS is characterized by excessive tachycardia and other symptoms upon standing, significantly impacting quality of life. This study aims to evaluate the clinical and laboratory findings in pediatric patients with post-COVID-19 or post-COVID-19 vaccine OI and POTS. Methods This retrospective chart review included pediatric patients under 18 years of age with chronic dizziness or syncope following COVID-19 infection or vaccination. Autonomic studies, including the tilt table test, Valsalva maneuver, deep breathing test, and Quantitative Sudomotor Axon Reflex Test (QSART), were conducted to assess autonomic function. Data on clinical symptoms, autonomic testing results, and sweat production were collected and analyzed. Results In total, 16 patients (mean age 15 ± 3 years) were included in the study, with 14 patients developing symptoms post-COVID-19 infection and two post-vaccination. Ten patients (62.5%) met the criteria for POTS, with an average delta heart rate of 49 bpm on tilt table testing. Seven patients (43.75%) showed abnormal results on the Valsalva maneuver, and 50% (four patients) of those who underwent QSART demonstrated small fiber neuropathy. The mean standing norepinephrine level was 520 picograms per milliliter (pg/mL), with some patients showing markedly elevated levels. Conclusion This study highlights the growing incidence of POTS and other forms of OI in pediatric patients following COVID-19 infection and vaccination, supporting the link between COVID-19 and autonomic dysfunction in children. Our findings contribute to the growing body of literature on Long-COVID and emphasize the need for greater awareness, as well as further research into its long-term autonomic effects.}, } @article {pmid39738536, year = {2024}, author = {Changela, S and Ashraf, S and Lu, JY and Duong, KE and Henry, S and Wang, SH and Duong, TQ}, title = {New-onset gastrointestinal disorders in COVID-19 patients 3.5 years post-infection in the inner-city population in the Bronx.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31850}, pmid = {39738536}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; *Gastrointestinal Diseases/epidemiology/virology/complications ; Retrospective Studies ; Aged ; Risk Factors ; Adult ; SARS-CoV-2/isolation & purification ; Incidence ; New York City/epidemiology ; Urban Population ; Proportional Hazards Models ; }, abstract = {This study examined the incidence, characteristics, and risk factors of new gastrointestinal disorders (GID) associated with SARS-CoV-2 infection up to 3.5 years post-infection. This retrospective study included 35,102 COVID-19 patients and 682,594 contemporary non-COVID-19 patients without past medical history of GID (controls) from the Montefiore Health System in the Bronx (3/1/2020 to 7/31/2023). Comparisons were made with unmatched and propensity-matched (1:2) controls. The primary outcome was new GID which included peptic ulcer, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, diverticulitis, and biliary disease. Multivariate Cox proportional hazards model analysis was performed with adjustment for covariates. There were 2,228 (6.34%) COVID-19 positive patients who developed new GID compared to 38,928 (5.70%) controls. COVID-19 patients had an elevated risk of developing new GID (adjusted HR = 1.18 (95% CI 1.12-1.25) compared to propensity-matched controls, after adjusting for confounders that included smoking, obesity, diabetes, hypertension. These findings underscore the need for additional research and follow-up of at-risk individuals for developing GID post infection.}, } @article {pmid39737451, year = {2024}, author = {Ng, QX and Wee, LE and Lim, YL and Ong, RHS and Ong, C and Venkatachalam, I and Liew, TM}, title = {Piecing together the narrative of #longcovid: an unsupervised deep learning of 1,354,889 X (formerly Twitter) posts from 2020 to 2023.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1491087}, pmid = {39737451}, issn = {2296-2565}, mesh = {*Social Media ; Humans ; *COVID-19/epidemiology ; *Deep Learning ; Narration ; SARS-CoV-2 ; Unsupervised Machine Learning ; }, abstract = {OBJECTIVE: To characterize the public conversations around long COVID, as expressed through X (formerly Twitter) posts from May 2020 to April 2023.

METHODS: Using X as the data source, we extracted tweets containing #long-covid, #long_covid, or "long covid," posted from May 2020 to April 2023. We then conducted an unsupervised deep learning analysis using Bidirectional Encoder Representations from Transformers (BERT). This method allowed us to process and analyze large-scale textual data, focusing on individual user tweets. We then employed BERT-based topic modeling, followed by reflexive thematic analysis to categorize and further refine tweets into coherent themes to interpret the overarching narratives within the long COVID discourse. In contrast to prior studies, the constructs framing our analyses were data driven as well as informed by the tenets of social constructivism.

RESULTS: Out of an initial dataset of 2,905,906 tweets, a total of 1,354,889 unique, English-language tweets from individual users were included in the final dataset for analysis. Three main themes were generated: (1) General discussions of long COVID, (2) Skepticism about long COVID, and (3) Adverse effects of long COVID on individuals. These themes highlighted various aspects, including public awareness, community support, misinformation, and personal experiences with long COVID. The analysis also revealed a stable temporal trend in the long COVID discussions from 2020 to 2023, indicating its sustained interest in public discourse.

CONCLUSION: Social media, specifically X, helped in shaping public awareness and perception of long COVID, and the posts demonstrate a collective effort in community building and information sharing.}, } @article {pmid39736592, year = {2024}, author = {Alkhormani, AA and Alghamdi, RA and Damdam, YA and Almaghrabi, ME and Alamri, FF and Khan, MA and Hakami, AY}, title = {Post-COVID-19 manifestations among college students: shedding the light on young adults' health.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {3613}, pmid = {39736592}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Cross-Sectional Studies ; Saudi Arabia/epidemiology ; Young Adult ; *Students/statistics & numerical data/psychology ; Adult ; Universities ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Adolescent ; Prevalence ; Depression/epidemiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID-19 syndrome refers to a variety of symptoms that affect different organs in the body and can persist 28 days following exposure to COVID-19. Previous studies have shown that COVID-19 affects not only elderly individuals but also young adults. However, the influence of post-COVID-19 syndrome on young adults has not been studied sufficiently. Therefore, the aim of this study was to determine the prevalence and characteristics of post-COVID-19 manifestations in young adults.

METHODS: An analytical cross-sectional online questionnaire was distributed from July 2022 to July 2023 to health sciences students in Saudi Arabia. The study used a non-probability convenience sampling technique, and the sample size was calculated to be 464. The survey included questions about the participants' demographics, health records, COVID-19 results, duration of infection, and previous and current COVID-19 symptoms. Illness severity and management were evaluated using the COVID Experiences (COVEX) Symptoms and Diagnoses module, and Patient Health Questionnaire (PHQ-9) was used to assess depression.

RESULTS: According to the inclusion criteria, 428 participants were divided into three groups: those who fully recovered within 14 days of the acute phase (76.4%), those with prolonged symptoms that resolved within 28 days (16.8%), and those with persistent symptoms for more than 28 days (6.8%). The symptom development frequency during the acute phase significantly differed among the three groups: headache (p = 0.038), loss of smell and taste (p = < 0.001), and fatigue (p = 0.009). The symptoms that significantly differed between the prolonged group and persistent group during the post-COVID-19 syndrome phase were loss of smell and taste (p = < 0.001) and shortness of breath (p = < 0.001). The study results revealed that females are susceptible to long-COVID-19. This study revealed that the overall severity of post-COVID-19 symptoms was mild in this age group. The PHQ-9 score when comparing the three groups showed a significant association with depression (p = 0.035).

CONCLUSION: The study results support the perception that not only can the geriatric population suffer from post-COVID-19 syndrome but also that young adults are prone to persistent symptoms such as loss of smell and taste, which may affect their mental health status.}, } @article {pmid39735263, year = {2024}, author = {Camici, M and Del Duca, G and Brita, AC and Antinori, A}, title = {Connecting dots of long COVID-19 pathogenesis: a vagus nerve- hypothalamic-pituitary- adrenal-mitochondrial axis dysfunction.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1501949}, pmid = {39735263}, issn = {2235-2988}, mesh = {Humans ; *Mitochondria/metabolism ; *Hypothalamo-Hypophyseal System/metabolism/virology ; *COVID-19/immunology/physiopathology/virology ; *Vagus Nerve/physiopathology ; *SARS-CoV-2 ; *Pituitary-Adrenal System/virology ; Post-Acute COVID-19 Syndrome ; Hydrocortisone/metabolism ; Acetylcholine/metabolism ; }, abstract = {The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function.}, } @article {pmid39733211, year = {2024}, author = {Karkabayeva, A and Mirakhmedova, K and Khusinova, S and Mamasaidov, A and Baimukhamedov, C}, title = {COVID-19 is a trigger of autoimmune rheumatic diseases: a hypothesis tested over time.}, journal = {Rheumatology international}, volume = {45}, number = {1}, pages = {11}, pmid = {39733211}, issn = {1437-160X}, mesh = {Humans ; *COVID-19/epidemiology ; *Rheumatic Diseases/epidemiology/immunology ; *Autoimmune Diseases/epidemiology ; *SARS-CoV-2 ; Greece/epidemiology ; Prevalence ; Incidence ; }, abstract = {We discuss the paper recently published in Rheumatology Internationa. This article reflects on the prevalence of autoimmune rheumatic diseases (ARD) during the COVID-19 pandemic (2020-2023) and compares the same with the pre-pandemic period (2016-2019). We assume that SARS-CoV-2 triggers ARD. This study concerns the 10 million population of Greece, and this work convincingly confirms our hypothesis. Besides, four large cohort studies have demonstrated an increased incidence of autoimmune diseases after surviving COVID-19. Compared to the prepandemic period, all ARD increased, and RA growth in the index study reached a level of more than 20% during the pandemic. A similar trend was observed in our report covering four Central Asian republics, namely Kazakhstan, Kyrgyzstan, Uzbekistan, and Tajikistan. The alarming growth of ARDs due to the consequences of the pandemic can still be predicted for the coming years. Healthcare professionals worldwide should be aware of this hypothesis to plan their COVID-19, long COVID, and ARD diagnostic and therapeutic strategies. We agree with the authors of the index article that more resources and research studies are warranted to optimize the diagnosis and treatment of ARDs in this challenging time.}, } @article {pmid39733164, year = {2024}, author = {Lu, JY and Lu, JY and Wang, SH and Duong, KS and Hou, W and Duong, TQ}, title = {New-onset cardiovascular diseases post SARS-CoV-2 infection in an urban population in the Bronx.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31451}, pmid = {39733164}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Cardiovascular Diseases/epidemiology/etiology ; Male ; Female ; Middle Aged ; Aged ; Incidence ; *SARS-CoV-2/isolation & purification ; Urban Population/statistics & numerical data ; Adult ; New York City/epidemiology ; Risk Factors ; Hospitalization ; Aged, 80 and over ; }, abstract = {This study investigated the incidence of new-onset cardiovascular disorders up to 3.5 years post SARS-CoV-2 infection for 56,400 individuals with COVID-19 and 1,093,904 contemporary controls without COVID-19 in the Montefiore Health System (03/11/2020 to 07/01/2023). Outcomes were new incidence of major adverse cardiovascular event (MACE), arrhythmias, inflammatory heart disease, thrombosis, cerebrovascular disorders, ischemic heart disease and other cardiac disorders between 30 days and (up to) 3.5 years post index date. Results were also compared with a pre-pandemic cohort over similar observation duration (N = 64,541). Cumulative incidence and hazard ratios adjusted for competitive risks were analyzed. Compared to contemporary controls, hospitalized COVID-19 patients had significantly higher risk of developing MACE (aHR = 2.29, 95% confidence interval [2.27, 2.31], p < 0.001), arrhythmias (aHR = 2.54[2.50, 2.58], p < 0.001), inflammatory heart disease (aHR = 5.34[4.79, 5.96], p < 0.001), cerebrovascular (aHR = 2.05[2.00, 2.11], p < 0.001), other cardiac disorders (aHR = 2.31[2.26, 2.35], p < 0.001), thrombosis (aHR = 4.25[4.15, 4.36], p < 0.001), and ischemic heart disease (aHR = 1.89[1.86, 1.92], p < 0.001). Non-hospitalized COVID-19 patients had slightly higher risk of developing MACE (aHR = 1.04[1.03, 1.06], p < 0.001), arrhythmias (aHR = 1.10[1.08, 1.12], p < 0.001), inflammatory heart disease (aHR = 2.29 [2.03, 2.59], p < 0.001), cerebrovascular (aHR = 1.11[1.07, 1.15], p < 0.001), and ischemic heart disease (aHR = 1.10[1.08, 1.13], p < 0.001). Race and ethnicity were mostly not associated with increased risks (p > 0.05). aHRs with contemporary controls as a reference were similar to those with pre-pandemic cohort as a reference. We concluded that new incident cardiovascular disorders in COVID-19 patients, especially those hospitalized for COVID-19, were higher than those in controls. Identifying risk factors for developing new-onset cardiovascular disorders may draw clinical attention for the need for careful follow-up in at-risk individuals.}, } @article {pmid39732395, year = {2024}, author = {Wee, LE and Lim, JT and Jin Tan, JY and Li, J and Chiew, C and Yung, CF and Chong, CY and Lye, DC and Tan, KB}, title = {Long-term multi-systemic complications following SARS-CoV-2 Omicron and Delta infection in children: a retrospective cohort study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.12.017}, pmid = {39732395}, issn = {1469-0691}, abstract = {OBJECTIVES: Most studies on long-term sequelae of SARS-CoV-2-infection in children were conducted pre-Omicron and pre-dated vaccination rollout. We examined long-term risk of new-incident multi-systemic sequelae after SARS-CoV-2 Delta/Omicron infection in a multi-ethnic Asian pediatric population.

METHODS: Retrospective cohort study of Singaporean children aged 1- 17 years infected during Delta/Omicron BA.1/2 transmission, and contemporaneous test-negative groups. Cox-regression was utilized to estimate risks of new-incident sequelae at 31-300 days post-infection.

RESULTS: 267,952 SARS-CoV-2-infected children were included, together with 273,517 test-negatives. ≥95% were infected during Omicron. During Delta, 23.6% of infected cases were fully-vaccinated; during Omicron, 60.4% were fully-vaccinated. ≥98% had mild infection not requiring hospitalisation. Overall, there was modestly increased risk of long-term respiratory sequelae (adjusted-hazard-ratio,aHR=1.09[95%CI=1.01-1.18]) and specifically bronchitis (aHR=1.17[95%CI=1.06-1.29]) in the SARS-CoV-2-infected group versus test-negatives. During Delta, increased risk of endocrine conditions (eg. diabetes) was observed (aHR=3.63[95%CI=1.25-10.50]); while during Omicron, increased risk of bronchitis (aHR=1.09[95%CI=1.02-1.20]) was observed in COVID-19 cases versus test-negatives. Elevated risk of bronchitis was observed amongst unvaccinated COVID-19 cases (aHR=1.17[95%CI=1.06-1.29]) versus test-negatives, but not in individuals who had received ≥1 vaccine dose. Risks of chronic sequelae following COVID-19 hospitalisation were comparable to those following historical influenza hospitalisation; albeit reduced when compared to respiratory sequelae following historical hospitalisations for respiratory-syncytial-virus (RSV).

CONCLUSION: Evidence of chronic sequelae in organ systems other than the respiratory system was limited in a pediatric cohort predominantly infected with mild SARS-CoV-2 Omicron infection. Risks of chronic sequelae in hospitalized COVID-19 cases did not substantially differ from historical influenza hospitalisations. Elevated risk of bronchitis was observed following SARS-CoV-2 infection in children, versus test-negatives; similarly, increased risk of respiratory sequelae was documented post-RSV hospitalisation, including children under-5.}, } @article {pmid39731899, year = {2024}, author = {Serafim, LM and Guimarães, RF and Martins, LV and Freitas, GKF and Liberato, FMG and de Morais Giglio, GP and Rizzi, PHB and Moreira, HC and Martins, LA and de Souza Cruz, SC and da Silva, VA and Paro, FM}, title = {Mobile application development to improve the active search for functional impairment and persistent symptoms in individuals post-COVID-19.}, journal = {Semergen}, volume = {51}, number = {4}, pages = {102430}, doi = {10.1016/j.semerg.2024.102430}, pmid = {39731899}, issn = {1578-8865}, abstract = {OBJECTIVES: This study aimed to develop a mobile application (App) to be used by primary care teams in the active search for functional impairment, long-term symptoms, and disabilities in individuals who have recovered from COVID-19, contributing to early treatment and referrals for multidisciplinary care and rehabilitation. This experimental study used the minimum viable product (MVP) methodology to develop an App named ReabilitaCOVID.

METHODS: This methodology involves ideation, content creation, prototype creation, usability tests, and adjustments based on feedback. The study was conducted in Brazil, and the population of the study included community health workers, who were the App's target users, and individuals from the community who had previously had COVID-19 and were at risk of developing PCS.

RESULTS: The App included a sociodemographic questionnaire, a clinical questionnaire, the post-COVID-19 Functional Status Scale (PCFS), the Modified Medical Research Council (MRC) Dyspnea Scale, and a flowchart. Usability tests were conducted, with feedback collected and adjustments made for improvements. Barriers to community health workers' use of the application were identified.

CONCLUSION: A tailored app was developed for primary care teams to use in the active search for PCS. Functional and usability tests were performed in simulated and real environments. The App has the potential to facilitate referrals for multidisciplinary care and rehabilitation efficiently, and it will be available freely to public health care services. MVP is a suitable approach for developing a tailored App for healthcare teams.}, } @article {pmid39731771, year = {2024}, author = {Pribylov, SA and Maslova, TA and Pribylov, VS and Leonidova, KO and Pribylova, NN and Kuts, AP}, title = {[Long-COVID, severe course, with congenital bronchiectasis, Williams-Campbell syndrome. Case report].}, journal = {Terapevticheskii arkhiv}, volume = {96}, number = {11}, pages = {1089-1095}, doi = {10.26442/00403660.2024.11.202997}, pmid = {39731771}, issn = {0040-3660}, mesh = {Humans ; Female ; *COVID-19/complications/diagnosis/therapy ; *Bronchiectasis/diagnosis ; Adolescent ; SARS-CoV-2 ; Lung Transplantation/methods ; Williams Syndrome/diagnosis/complications ; Lung/abnormalities/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; }, abstract = {We present a clinical observation of an 18-year-old female patient with congenital bronchiectasis combined with congenital cystic degeneration of the upper lobes of both lungs, Williams-Campbell syndrome, long-COVID, severe course. The patient was treated in infectious disease department (three times), with subsequent transfer to pulmonology department of Kursk Regional Multi-Purpose Clinical Hospital from 31.01.2023 to 02.05.2023. The patient was going to have lung transplantation, registered in Shumakov Federal Research Center of Transplantology and Artificial Organs earlier. The patient was transported by air ambulance escorted by the resuscitation team to the Shumakov Federal Research Center of Transplantology and Artificial Organs on 02.05.2023 with negative PCR COVID-19 test. The literature data on the frequency of association of these diseases, clinical features, criteria for diagnosis and treatment, indications for lung transplantation are presented.}, } @article {pmid39730204, year = {2024}, author = {Liang, KH and Chen, YC and Hsu, CY and Kao, ZK and Tsai, PH and Huang, HY and Chu, YC and Ho, HL and Liao, YC and Lee, YC and Huang, CC and Wei, TC and Liao, YJ and Lu, YH and Kuo, CT and Chiou, SH}, title = {Predictive biosignatures for hospitalization in patients with virologically confirmed COVID-19.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001203}, pmid = {39730204}, issn = {1728-7731}, abstract = {BACKGROUND: COVID-19, caused by the SARS-CoV-2 virus, presents with varying severity among individuals. Both viral and host factors can influence the severity of acute and chronic COVID-19, with chronic COVID-19 commonly referred to as long COVID. SARS-CoV-2 infection can be properly diagnosed by performing real-time reverse transcription PCR analysis of nasal swab samples. Pulse oximetry, chest X-ray, and complete blood count (CBC) analysis can be used to assess the condition of the patient to ensure that the appropriate medical care is delivered. This study aimed to develop biosignatures that can be used to distinguish between patients who are likely to develop severe disease and require hospitalization from patients who can be safely monitored in less intensive settings.

METHODS: A retrospective investigation was conducted on 7897 adult patients with virologically confirmed SARS-CoV-2 infection between January 26, 2020, and November 30, 2023; all patients underwent comprehensive CBC testing at Taipei Veterans General Hospital). Among them, 1867 patients were independently recruited for a population study involving genome-wide genotyping of approximately 424 000 genomic variants. Therefore, the participants were divided into two patient cohorts, one with genomic data (n = 1867) and one without (n = 6030) for model validation and training, respectively.

RESULTS: We constructed and validated a biosignature model by using a combination of CBC measurements to predict subsequent hospitalization events (hazard ratio [95% confidence interval] = 3.38, [3.07, 3.73] for the training cohort and 3.03 [2.46, 3.73] for the validation cohort; both p < 10-8). The obtained scores were used to identify the top quartile of patients, who formed the "very high risk" group with a significantly higher cumulative incidence of hospitalization (log-rank p < 10-8 in both the training and validation cohorts). The "very high risk" group exhibited a cumulative hospitalization rate of >60%, whereas the rate for the other patients was approximately 30% over a 1.5-year period, providing a binary classification of patients with distinct hospitalization risks. To investigate the genetic factors mediating this risk, we conducted a genome-wide association study. Specific regions in chromosomes 7 and 10 and the mitochondrial chromosome (M), harboring IKZF1, ABLIM1 and MT-ND3, exhibited prominent associations with binary risk classification. The identified exonic variants of IKZF1 are linked to several autoimmune diseases. Notably, people with different genotypes of the leading variants (rs4132601, rs141492519, and Affx-120744614) exhibited varying cumulative hospitalization rates following infection.

CONCLUSION: We successfully developed and validated a biosignature model of COVID-19 severe disease in virologically confirmed patients. The identified genomic variants provide new insights for infectious disease research and medical care.}, } @article {pmid39727505, year = {2024}, author = {Pour Mohammadi, S and Etesamipour, R and Mercado Romero, F and Peláez, I}, title = {A Step Forward in Long COVID Research: Validating the Post-COVID Cognitive Impairment Scale.}, journal = {European journal of investigation in health, psychology and education}, volume = {14}, number = {12}, pages = {3001-3018}, pmid = {39727505}, issn = {2254-9625}, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection, includes a variety of enduring symptoms that endure beyond the acute phase of the illness, impacting multiple facets of patients' psychological and physical health. The persistent symptoms encompass fatigue, breathing difficulties, musculoskeletal pain, and cognitive impairments, which can significantly affect daily functioning and overall quality of life. The objective of this study was to create and validate the accuracy of the Post-COVID Cognitive Impairment Scale, which is used to evaluate cognitive impairments resulting from a COVID-19 infection. This study was conducted in Iran between January and September 2023. It consisted of three phases: developing the scale, evaluating its content validity with experts, and validating its structure with 454 participants using exploratory and confirmatory factor analysis. The exploratory factor analysis revealed two variables, namely memory and attention, which accounted for 40.38% of the variation. Confirmatory factor analysis verified the model's fit, with indices indicating satisfactory alignment: CMIN/DF = 2.80, RMSEA = 0.06, SRMR = 0.05, CFI = 0.93, and TLI = 0.92. The factor loadings were statistically significant (p < 0.001), and Cronbach's Alpha values indicated strong internal consistency (working memory = 0.81, attention = 0.80). These results affirm the Post-COVID Cognitive Impairment Scale is a valid and reliable instrument for evaluating cognitive deficiencies in individuals with long COVID. Its application in clinical and research environments aids in the prompt detection and tracking of the treatment of such impairments.}, } @article {pmid39727052, year = {2025}, author = {Scheibenbogen, C and Wirth, KJ}, title = {Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {1}, pages = {e13669}, pmid = {39727052}, issn = {2190-6009}, support = {//Weidenhammer Zoebele Foundation/ ; //Lost Voices Foundation/ ; //MECFS Research Foundation/ ; //Fatigatio e.V./ ; //German Research Foundation/ ; //German Ministry of Education and Science/ ; //German Ministry of Health (BMG)/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology ; Mitochondria/metabolism ; *Muscle, Skeletal/cytology/physiopathology ; *Post-Acute COVID-19 Syndrome/physiopathology/virology ; SARS-CoV-2/pathogenicity ; }, abstract = {BACKGROUND: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.

METHODS: We collect, summarize and discuss the current state of knowledge for the key role of skeletal muscle pathophysiology. We try to explain which risk factors and mechanisms are responsible for a subgroup of patients with post COVID syndrome (PCS) to develop ME/CFS (PC-ME/CFS).

RESULTS: Mitochondrial dysfunction is a long-held assumption to explain cardinal symptoms of ME/CFS. However, mitochondrial dysfunction could not be convincingly shown in leukocytes. By contrast, recent studies provide strong evidence for mitochondrial dysfunction in skeletal muscle tissue in ME/CFS. An electron microscopy study could directly show damage of mitochondria in skeletal muscle of ME/CFS patients with a preferential subsarcolemmal localization but not in PCS. Another study shows signs of skeletal muscle damage and regeneration in biopsies taken one day after exercise in PC-ME/CFS. The simultaneous presence of necroses and signs of regeneration supports the concept of repeated damage. Other studies correlated diminished hand grip strength (HGS) with symptom severity and prognosis. A MRI study showed that intracellular sodium in muscles of ME/CFS patients is elevated and that levels correlate inversely with HGS. This finding corroborates our concept of sodium and consecutive calcium overload as cause of muscular and mitochondrial damage caused by enhanced proton-sodium exchange due to anaerobic metabolism and diminished activity of the sodium-potassium-ATPase. The histological investigations in ME/CFS exclude ischemia by microvascular obstruction, viral presence or immune myositis. The only known exercise-induced mechanism of damage left is sodium induced calcium overload. If ionic disturbance and mitochondrial dysfunction is severe enough the patient may be captured in a vicious circle. This energy deficit is the most likely cause of exertional intolerance and post exertional malaise and is further aggravated by exertion.

CONCLUSION: Based on this pathomechanism, future treatment approaches should focus on normalizing the cause of ionic disbalance. Current treatment strategies targeting hypoperfusion have the potential to improve the dysfunction of ion transporters.}, } @article {pmid39726863, year = {2024}, author = {Mallari, P and Taulier, T and Kamal, MA}, title = {Recovery From Long COVID: The Role of Bioelectric Meridian Therapy in Restoring Health and Well-Being.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76279}, pmid = {39726863}, issn = {2168-8184}, abstract = {This case report explores the journey to a healthier life of a 57-year-old man who stayed athletic after contracting COVID-19 during a trip to a foreign country. He had minimal symptoms in the beginning. He started with a dull cough, but the symptoms then progressed to loss of taste and smell, mental fatigue, and nerve problems. In this case study, traditional cures helped only to some extent. Out of frustration with these symptoms, the patient started bioelectric meridian therapy (BMT) in August 2021 and benefited from it. The patient described progressive sensation, cognition, and muscle power enhancement during six months of BMT sessions. The therapy relieved the muscles' stiffness and regulated the bio-energy circulation to improve the general quality of life and ease physical exertion operations. The case affirms how supportive modalities such as BMT help handle the after-effects of COVID-19. The patients' recovery involved precise mental concentration, return of appetite, and regained vigor, which improved the patient's life. This case report shows how integrative approaches may be helpful when it comes to the reactivation of health processes after virus infection.}, } @article {pmid39724975, year = {2024}, author = {Skevaki, C and Moschopoulos, CD and Fragkou, PC and Grote, K and Schieffer, E and Schieffer, B}, title = {Long-COVID - pathophysiology, current concepts and future directions.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2024.12.1074}, pmid = {39724975}, issn = {1097-6825}, abstract = {Long-COVID, an umbrella term referring to a variety of symptoms and clinical presentations, which emerge in a subset of patients after SARS-CoV-2 infection, has a significant impact on an individual's quality of life and places a substantial burden on healthcare systems worldwide, straining financial and human resources. The pathophysiology of long-COVID remains incompletely understood, though several hypotheses have been proposed to explain different aspects of this complex condition. SARS-CoV-2 persistence, direct organ damage, innate and adaptive immune system pertubation, autoimmunity, latent viruses reactivation, endothelial dysfunction, and microbiome disturbances are among the most relevant avenues for elucidating the evolution, complexity, and mechanisms of long-COVID. Active investigation regarding potential biomarkers for long-COVID and its associated disease endotypes highlights the role of inflammatory mediators, immunophenotyping and multi-omics approaches. Further advances in understanding long-COVID are needed to inform current and future therapeutics.}, } @article {pmid39723824, year = {2024}, author = {Mai, X and Hu, Y and Wu, Z and Guo, X and Dong, M and Jia, L and Ren, J}, title = {Self-Assembly of Human Fibrinogen into Microclot-Mimicking Antifibrinolytic Amyloid Fibrinogen Particles.}, journal = {ACS applied bio materials}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsabm.4c01651}, pmid = {39723824}, issn = {2576-6422}, abstract = {Recent clinical studies have highlighted the presence of microclots in the form of amyloid fibrinogen particles (AFPs) in plasma samples from Long COVID patients. However, the clinical significance of these abnormal, nonfibrillar self-assembly aggregates of human fibrinogen remains debated due to the limited understanding of their structural and biological characteristics. In this study, we present a method for generating mimetic microclots in vitro. Using this approach, the self-assembly process, structural organization of AFPs, and their interactions with human plasma components were elucidated. The amyloid transition of fibrinogen occurs under acidic conditions within a pH range of 2.3-3.2. Well-dispersed amyloid oligomers of fibrinogen, ranging in size from 1 to 5 μm, can be prepared at pH 2.8 after 1 h of incubation. We tracked the dynamic self-assembly process at the single-molecule level using high-speed atomic force microscopy (HS-AFM). The arrangement of amyloid oligomers manifests as well-ordered, stacked nanodomains with striped patterns, growing perpendicular to the primary axis of the fibrinogen monomer. Upon transfer to physiological solution conditions or human plasma, these amyloid oligomers further aggregate into nonfibrillar structures at the micrometer scale, resembling the microclots observed in the bloodstream of Long COVID patients. Notably, these AFPs exhibit characteristics consistent with microclots, including positive staining in thioflavin T (ThT) assays and resistance to fibrinolysis. Proteomic analysis suggests that AFPs interact with various components of human plasma and have an enhanced binding affinity with complement C3 compared to native fibrinogen. This study enables the in vitro preparation of mimetic microclots exhibiting amyloid features. It is anticipated to facilitate further researches on the mechanisms, detection, and treatment of diseases associated with fibrinogen amyloidogenesis.}, } @article {pmid39723582, year = {2024}, author = {Luedke, JC and Vargas, G and Malone, LA and Parker, KH and Ng, R}, title = {Utility of teleneuropsychology services among pediatric patients with long COVID.}, journal = {The Clinical neuropsychologist}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/13854046.2024.2445269}, pmid = {39723582}, issn = {1744-4144}, abstract = {Objective: To determine the clinical utility of teleneuropsychology (teleNP) services in screening for cognitive concerns in a population of children and adolescents presenting with long COVID. Method: This cross-sectional study evaluated 76 pediatric patients (64% female, Mage = 13.48, SD = 2.97, range = 5 to 18 years) with long COVID referred for a neuropsychological evaluation due to persistent cognitive symptoms following their COVID infection. Of these 76 patients, 33 were tested in person, while 43 were tested via teleNP at home. Patients were administered a brief testing battery designed for use in-person or through teleNP services. Tests administered included the WASI-II (Intellectual Functioning), D-KEFS Verbal Fluency (Executive Functioning/Shifting), Oral Version of the Symbol Digit Modalities Test (Processing Speed), ChAMP List (Learning and Memory), WAIS-IV/WISC-V Digit Span (Working Memory), and TEA-Ch Score and Score DT (Sustained Auditory Attention and Divided Attention). Differences in scores between those evaluated in-person or teleNP were computed using analyses of variance and Bayesian statistics across measures. Differences in the proportion of those scoring in the below average range (< 9[th] percentile) were also computed. Results: Findings revealed similar performance for patients tested in-person and patients tested by teleNP modality across measures. Conclusions: The present study provides preliminary evidence for the clinical utility of teleNP services in pediatric long COVID patients on a cognitive screening battery. These results lend support for expanding teleNP services to pediatric patients with long COVID to assess neurocognitive functioning, which is particularly important given scarcity of specialty long COVID clinics.}, } @article {pmid39722909, year = {2024}, author = {Mukhida, S and Khan, S}, title = {Does long covid-19 affect the quality of life only to Covid-19 patients or family member also?.}, journal = {Journal of family medicine and primary care}, volume = {13}, number = {11}, pages = {5442-5443}, pmid = {39722909}, issn = {2249-4863}, } @article {pmid39722811, year = {2024}, author = {Matviichuk, A and Yerokhovych, V and Zemskov, S and Ilkiv, Y and Gurianov, V and Shaienko, Z and Falalyeyeva, T and Sulaieva, O and Kobyliak, N}, title = {Unveiling risk factors for post-COVID-19 syndrome development in people with type 2 diabetes.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1459171}, pmid = {39722811}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/epidemiology ; *COVID-19/complications/epidemiology ; Female ; Male ; Middle Aged ; Risk Factors ; *Post-Acute COVID-19 Syndrome ; Aged ; Adult ; Ukraine/epidemiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Post-COVID-19 syndrome (PCS) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated chronic condition characterized by long-term violations of physical and mental health. People with type 2 diabetes (T2D) are at high risk for severe COVID-19 and PCS.

AIM: The current study aimed to define the predictors of PCS development in people with T2D for further planning of preventive measures and improving patient outcomes.

MATERIALS AND METHODS: The data were collected through the national survey targeting persons with T2D concerning the history of COVID-19 course and signs and symptoms that developed during or after COVID-19 and continued for more than 12 weeks and were not explained by an alternative diagnosis. In total, 469 patients from different regions of Ukraine were enrolled in the study. Among them, 227 patients reported PCS development (main group), while 242 patients did not claim PCS symptoms (comparison group). Stepwise multivariate logistic regression and probabilistic neural network (PNN) models were used to select independent risk factors.

RESULTS: Based on the survey data, 8 independent factors associated with the risk of PCS development in T2D patients were selected: newly diagnosed T2D (OR 4.86; 95% CI 2.55-9.28; p<0.001), female sex (OR 1.29; 95% CI 0.86-1.94; p=0.220), COVID-19 severity (OR 1.35 95% CI 1.05-1.70; p=0.018), myocardial infarction (OR 2.42 95% CI 1.26-4.64; p=0.002) and stroke (OR 3.68 95% CI 1.70-7.96; p=0.001) in anamnesis, HbA1c above 9.2% (OR 2.17 95% CI 1.37-3.43; p=0.001), and the use of insulin analogs (OR 2.28 95% CI 1.31-3.94; p=0.003) vs human insulin (OR 0.67 95% CI 0.39-1.15; p=0.146). Although obesity aggravated COVID-19 severity, it did not impact PCS development. In ROC analysis, the 8-factor multilayer perceptron (MLP) model exhibited better performance (AUC 0.808; 95% CІ 0.770-0.843), allowing the prediction of the risk of PCS development with a sensitivity of 71.4%, specificity of 76%, PPV of 73.6% and NPV of 73.9%.

CONCLUSIONS: Patients who were newly diagnosed with T2D, had HbA1c above 9.2%, had previous cardiovascular or cerebrovascular events, and had severe COVID-19 associated with mechanical lung ventilation were at high risk for PCS.}, } @article {pmid39721883, year = {2024}, author = {Chang, LY and Ang, MF and Salim, MS and Musib, AF}, title = {Evaluation of Vocal and Pulmonary Health Through Acoustic Analysis of Voice and Respiratory Measurements in People With Long COVID-19 Symptoms.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2024.11.018}, pmid = {39721883}, issn = {1873-4588}, abstract = {BACKGROUND/OBJECTIVES: The coronavirus disease (COVID-19) pandemic has significantly impacted global health, with Malaysia reporting over 5 million cases as of May 2024. While symptoms like fatigue and breathlessness are commonly reported among COVID-19 patients, limited research exists on the vocal and pulmonary conditions of individuals with long COVID symptoms. This study aims to assess vocal impairments and pulmonary function differences between long COVID patients and healthy controls, addressing gaps in understanding how long COVID affects vocal and respiratory health. Additionally, it seeks to identify gender-specific differences to inform targeted rehabilitation programs.

METHODS: The study included 140 participants, divided into two groups: an experimental group (long COVID patients) and a control group (healthy individuals). Participants completed questionnaires and underwent acoustic voice and pulmonary/lung function measurements in a controlled environment at Universiti Putra Malaysia (UPM). Vocal parameters measured were F0, F0SD, jitter, shimmer, harmonic-to-noise ratio, cepstral peak prominence (CPP), H1-H2, maximum phonation time (MPT), and number of voice break (NVB), while pulmonary function was assessed using forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the FEV1/FVC ratio.

RESULTS: Significant differences were found between the long COVID and control groups in several vocal acoustic parameters (F0, jitter, shimmer, CPP, MPT, and H1-H2) and pulmonary function measures (FEV1, FEV1/FVC ratio). Gender-specific differences included males showing significant differences in shimmer, CPP, H1-H2, MPT, and FVC (combined obstructive and restrictive conditions), while females showed differences in F0, jitter, shimmer, and H1-H2. Both genders exhibited obstructive lung conditions.

CONCLUSION: The study investigated vocal and pulmonary function impairments in individuals experiencing long COVID symptoms compared with healthy controls. Significant differences in vocal acoustic and pulmonary parameters were observed between the two groups. This study identified changes in vocal acoustic and pulmonary parameters associated with long COVID, highlighting the need for targeted rehabilitation programs to support recovery in affected patients, providing insights into potential rehabilitation programs for long COVID patients.}, } @article {pmid39721744, year = {2024}, author = {Takaoka, H and Kawada, I and Hiruma, G and Nagashima, K and Terai, H and Ishida, N and Namkoong, H and Asakura, T and Masaki, K and Miyata, J and Chubachi, S and Ohgino, K and Otsuka, K and Miyao, N and Odani, T and Watase, M and Baba, R and Okamori, S and Arai, D and Nakachi, I and Kuwahara, N and Fujiwara, A and Okada, T and Ishiguro, T and Isono, T and Ishii, M and Sato, Y and Fukunaga, K}, title = {Long COVID among the first three waves of COVID-19 in Japan: a multicentre cohort study.}, journal = {BMJ open respiratory research}, volume = {11}, number = {1}, pages = {}, pmid = {39721744}, issn = {2052-4439}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Japan/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Prospective Studies ; *SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Adult ; Comorbidity ; Risk Factors ; Aged, 80 and over ; Cohort Studies ; }, abstract = {OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 significantly impacts Japan with a high number of infections and deaths reported. Long coronavirus disease (COVID) characterised by persistent symptoms after COVID-19 has gained recognition but varies across studies. This study aimed to investigate the differences in long COVID among patients hospitalised during Japan's first three waves of the pandemic.

DESIGN: Multicentre prospective cohort study.

SETTING: 26 medical facilities across Japan between February 2020 and February 2021.

PARTICIPANTS: In total, 1066 hospitalised patients diagnosed with COVID-19 were included with 206, 301 and 559 patients in the first, second and third waves, respectively. Data were collected using electronic data capture and patient-reported outcome forms.

Long COVID was assessed at 3, 6 and 12 months after COVID-19 diagnosis.

RESULTS: Significant differences were observed between the waves in various baseline and clinical characteristics such as age, body mass index (BMI), comorbidities, the severity of COVID-19, complications and treatment during hospitalisation. Long COVID, particularly dyspnoea, was most prevalent in the first wave. Multivariate logistic regression analysis confirmed a significant positive association between the first wave and long COVID including dyspnoea after adjusting for age, sex, BMI, smoking status and COVID-19 severity.

CONCLUSIONS: Patients hospitalised during the first wave had a higher risk of experiencing long COVID, especially dyspnoea, than those hospitalised during the other waves. These findings underscore the need for continued monitoring and managing long COVID in COVID-19 survivors, particularly in those hospitalised during the first wave.

TRIAL REGISTRATION NUMBER: UMIN000042299.}, } @article {pmid39721309, year = {2024}, author = {Frisk, B and Jürgensen, M and Espehaug, B and Søfteland, E and Kvale, G}, title = {Sustained improvements in sick leave, fatigue and functional status following a concentrated micro-choice based treatment for patients with long COVID: A 1 year prospective uncontrolled study.}, journal = {Journal of psychosomatic research}, volume = {189}, number = {}, pages = {112023}, doi = {10.1016/j.jpsychores.2024.112023}, pmid = {39721309}, issn = {1879-1360}, abstract = {BACKGROUND: Long COVID has affected approximately 200 million people globally, with substantial consequences for the individuals, healthcare systems and society. Treatment guidelines lack clear recommendations regarding increased activity. This study aimed to evaluate primary outcomes as patients' satisfaction, illness perception and patient activation. In addition, potential changes in functional levels, sick leave, fatigue, dyspnea, and exercise capacity from baseline to 12-month follow-up after a concentrated micro-choice-based intervention in patients with long COVID.

METHODS: This prospective interventional study, study start 26 May 2021, with 12-month follow-up included 78 patients with long COVID aged 19-67 years, mean age 40.3 ± 12.0 years. The intervention was structured into three equally important phases: pre-treatment preparation, a 3-day concentrated micro-choice-based intervention and integrating the changes into everyday living.

RESULTS: At 3 and 12-month follow-ups, 71 (91 %) and 65 (83 %) patients, respectively completed questionnaires and physical tests. The patients reported significant enhancements in illness perception and health activation. Sick leave decreased significantly from 63 % at baseline to 43 % and 23 % at 3 and 12-month, respectively (p < 0.001). Fatigue decreased significantly at 3-month (mean difference (MD) = -5.5, 95 % CI: -6.6 to -4.3) and at 12-month (MD = -7.0, CI: -8.3 to -5.7). Functional level and exercise capacity increased (p < 0.001), and dyspnea decreased (p < 0.001), at both follow-ups regardless of baseline fatigue severity.

CONCLUSION: The micro-choice-based intervention for patients with long COVID was safe, highly satisfactory and significantly enhanced health activation alongside rapid improvements in functional levels and fatigue which continued improving throughout the follow-up year, together with significant reduction in sick leave.}, } @article {pmid39721163, year = {2024}, author = {Ridge, DT and Broom, A and Alwan, NA and Chew-Graham, CA and Smyth, N and Gopal, D and Kingstone, T and Gaszczyk, P and Begum, S}, title = {Medical ambivalence and Long Covid: The disconnects, entanglements, and productivities shaping ethnic minority experiences in the UK.}, journal = {Social science & medicine (1982)}, volume = {366}, number = {}, pages = {117603}, doi = {10.1016/j.socscimed.2024.117603}, pmid = {39721163}, issn = {1873-5347}, abstract = {Structural violence - related to 'isms' like racism, sexism, and ableism - pertains to the ways in which social institutions harm certain groups. Such violence is critical to institutional indifference to the plight of ethnic minority people living with long-term health conditions. With only emergent literature on the lived experiences of ethnic minorities with Long Covid, we sought to investigate experiences around the interplay of illness and structural vulnerabilities. Thirty-one semi-structured interviews with a range of UK-based participants of varying ethnic minorities, ages and socio-economic situations were undertaken online between June 2022 and June 2023. A constant comparison analysis was used to develop three over-arching themes: (1) Long Covid and social recognition; (2) The violence of medical ambivalence; and (3) Pathways to recognition and support. Findings showed that while professional recognition and support were possible, participants generally faced the spectre and deployment of a particular mode of structural violence, namely 'medical ambivalence'. The contours of medical ambivalence in the National Health Service (NHS) as an institution had consequences, including inducing or accentuating suffering via practices of care denial. Despite multiple structurally shaped ordeals (like healthcare, community stigma, and sexism), many participants were nevertheless able to gain recognition for their condition (e.g. online, religious communities). Participants with more resources were in the best position to 'cobble together' their own approaches to care and support, despite structural headwinds.}, } @article {pmid39720706, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {The impact of COVID-19 on accelerating of immunosenescence and brain aging.}, journal = {Frontiers in cellular neuroscience}, volume = {18}, number = {}, pages = {1471192}, pmid = {39720706}, issn = {1662-5102}, abstract = {The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.}, } @article {pmid39720603, year = {2025}, author = {Wu, Q and Zhang, B and Tong, J and Bailey, LC and Bunnell, HT and Chen, J and Chrischilles, EA and Christakis, DA and Downs, SM and Hirabayashi, K and Mishkin, AD and Mosa, ASM and Pajor, NM and Rao, S and Razzaghi, H and Schwenk, HT and Sills, MR and Wang, H and Wang, L and Wang, Y and Zhang, D and Zhou, T and Jhaveri, R and Tchetgen Tchetgen, EJ and Morris, JS and Forrest, CB and Chen, Y and , }, title = {Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescents.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {102962}, pmid = {39720603}, issn = {2589-5370}, abstract = {BACKGROUND: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis.

METHODS: We conducted real-world vaccine effectiveness study and mediation analysis using data from twenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Three independent cohorts were constructed including adolescents (12-20 years) during the Delta phase (July 1-November 30, 2021), children (5-11 years) and adolescents (12-20 years) during the Omicron phase (January 1-November 30, 2022). The intervention is first dose of the BNT162b2 vaccine in comparison with no receipt of COVID-19 vaccine. The outcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)∗100 and mediating effects were reported as relative risks.

FINDINGS: 112,590 adolescents (88,811 vaccinated) were included in the cohort for the analysis against Delta variant, and 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) were included for the analysis against Omicron variant. During the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9%-97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3%-73.5%) and 75.1% (95% CI: 50.4%-87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimated relative risk of 1.08 (95% CI: 0.75-1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92-1.66) among children and 0.91 (95% CI: 0.69-1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03-0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23-0.42) among children and 0.21 (95% CI: 0.16-0.27) among adolescents during the Omicron period.

INTERPRETATION: Our study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccine's effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection.

FUNDING: National Institutes of Health.}, } @article {pmid39720104, year = {2025}, author = {Miwa, K}, title = {Oral minocycline therapy as first-line treatment in patients with Myalgic encephalomyelitis and long COVID: A pilot study.}, journal = {eNeurologicalSci}, volume = {38}, number = {}, pages = {100537}, pmid = {39720104}, issn = {2405-6502}, abstract = {BACKGROUND: Myalgic encephalomyelitis (ME) is associated with long COVID and also untoward sequelae after anti-coronavirus vaccination. Recently, oral minocycline therapy has been reported to ameliorate symptoms in patients with ME, particularly at the initial stage of the disease.

METHODS: Oral minocycline (100 mg × 2 on the first day, followed by 100 mg/day for 41 days) was administered to 55 patients with ME that emerged during the "Corona era," including 19 patients with long COVID and 5 patients diagnosed with untoward sequalae following coronavirus vaccination.

RESULTS: Acute adverse effects including nausea and/or dizziness caused four (7 %) patients to discontinue treatment in the first few days. Among the other 51 patients who completed therapy, favorable effects were observed, including a decrease in performance status score or index for restricted activities of daily living ≥2 points in 41 (80 %) patients. Disease duration was inversely associated with the favorable therapeutic effects (p = 0.02) and the disease duration within 6 months was significantly associated with the favorable therapeutic effects (27/30, 90 %, p = 0.02, hazard ratio: 3.6, 95 % confidence interval, 1.2-10.6). The favorable effects were observed in 16 (89 %) of 18 patients with long COVID. Significant amelioration of subjective symptoms of fatigue, post-exertional malaise, unrefreshing sleep, brain fog, disequilibrium, orthostatic intolerance, and neuropathic pain were observed.

CONCLUSIONS: Oral minocycline was effective at ameliorating symptoms in patients with ME including long COVID and post-coronavirus vaccination sequalae. It represents an effective first-line therapeutic option for these patients in the initial stage.}, } @article {pmid39719753, year = {2024}, author = {Li, Y and Xi, L and Wang, D and Fan, G and Li, X and Shi, Y and Chen, H and Deng, C and Chen, H and Luo, Q and Cheng, Z and Zhang, S and Zhang, Z and Zhang, Y and Gao, Q and Huang, Q and Xie, W and Zhai, Z and Wang, C and , }, title = {Risk of bleeding in pulmonary embolism patients concomitant with COVID-19 undergoing extended anticoagulation: A multicenter cohort study.}, journal = {Thrombosis research}, volume = {246}, number = {}, pages = {109237}, doi = {10.1016/j.thromres.2024.109237}, pmid = {39719753}, issn = {1879-2472}, abstract = {INTRODUCTION: The impact of Coronavirus disease 2019 (COVID-19) on clinical outcomes in pulmonary embolism (PE) patients receiving extended anticoagulation therapy is not fully understood. The study aimed to investigate the impact of the Omicron outbreak on patients with PE receiving extended anticoagulation therapy.

MATERIALS AND METHODS: This prospective multicenter cohort study was conducted during the Omicron pandemic. Patients diagnosed with PE between January 1, 2016, and September 1, 2022, who were on extended anticoagulation therapy, were recruited. The study compared VTE recurrence and bleeding events between COVID-19 and non-COVID-19 patients, using the propensity score weighting with overlap weights (PSOW) method for the final analysis.

RESULTS: A total of 521 patients with PE receiving extended anticoagulation therapy were enrolled. Patients suffering from COVID-19 had significantly higher bleeding rates (10.5 % vs 2.1 %, p = 0.001), with consistent results after PSOW (OR = 4.79, 95%CI [1.04-22.21], p = 0.045). No significant differences in VTE recurrence were observed between these two groups before and after weighting. During follow-up, 31 % of patients developed long COVID, with higher bleeding rates (14.6 % vs 3.5 %, p < 0.001). After PSOW, there was a significantly increased bleeding risk in patients with long COVID (HR = 3.29, 95%CI [1.28, 8.49]); Log-Rank test p < 0.001). Furthermore, a prior history of active malignancy (OR = 9.3; 95%CI [1.38, 59.98]), chronic kidney disease (OR = 13.98; 95%CI [1.59, 122.27]) and bleeding occurred during the acute phase of COVID-19 (OR = 23.73; 95%CI [5.20, 108.35]) were independent predictors of bleeding in patients with long COVID.

CONCLUSIONS: COVID-19 and long COVID are associated with an increased bleeding risk in PE patients undergoing extended anticoagulation therapy. This study emphasizes the need for close monitoring and optimization of anticoagulation strategies in PE patients.}, } @article {pmid39719158, year = {2024}, author = {Lemogne, C and Vedrines, CO and Capuron, L and Hoertel, N}, title = {Inflammation and Depressive Mood.}, journal = {Joint bone spine}, volume = {}, number = {}, pages = {105832}, doi = {10.1016/j.jbspin.2024.105832}, pmid = {39719158}, issn = {1778-7254}, } @article {pmid39718501, year = {2024}, author = {Parraga, G and Eddy, RL}, title = {Power Outage: Mitochondrial Dysfunction in Long COVID Measured Using [1]H and [31]P MR Spectroscopy.}, journal = {Radiology}, volume = {313}, number = {3}, pages = {e242833}, doi = {10.1148/radiol.242833}, pmid = {39718501}, issn = {1527-1315}, } @article {pmid39718498, year = {2024}, author = {Finnigan, LEM and Cassar, MP and Jafarpour, M and Sultana, A and Ashkir, Z and Azer, K and Neubauer, S and Tyler, DJ and Raman, B and Valkovič, L}, title = {[1]H and [31]P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.}, journal = {Radiology}, volume = {313}, number = {3}, pages = {e233173}, pmid = {39718498}, issn = {1527-1315}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Male ; Female ; Prospective Studies ; Adult ; *Magnetic Resonance Spectroscopy/methods ; *COVID-19/diagnostic imaging/metabolism/complications ; *Muscle, Skeletal/diagnostic imaging/metabolism ; Middle Aged ; Fatigue/metabolism/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mitochondria, Muscle/metabolism ; Phosphorus Isotopes ; Phosphocreatine/metabolism ; }, abstract = {Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms. MR spectroscopy was performed using a 3-T MRI system, measuring hydrogen 1 ([1]H) and phosphorus 31 ([31]P) during exercise and recovery in the gastrocnemius muscle. General linear models were used to compare the phosphocreatine recovery rate time constant (hereafter, τPCr) and maximum oxidative flux, also known as mitochondrial capacity (hereafter, Qmax), between groups. Pearson correlations were used to assess the relationship between MR spectroscopic parameters and fatigue scores. Results A total of 41 participants with PCC (mean age, 44 years ± 9 [SD]; 23 male) (mean body mass index [BMI], 26 ± 4) and 29 healthy control participants (mean age, 34 years ± 11; 18 male) (mean BMI, 23 ± 3) were included in the study. Participants with PCC showed higher resting phosphocreatine levels (mean difference, 4.10 mmol/L; P = .03). Following plantar flexion exercise in situ (3-5 minutes), participants with PCC had a higher τPCr (92.5 seconds ± 35.3) compared with controls (51.9 seconds ± 31.9) (mean difference, 40.6; 95% CI: 24.3, 56.6; P ≤ .001), and Qmax was higher in the control group, with a mean difference of 0.16 mmol/L per second (95% CI: 0.07, 0.26; P = .008). There was no correlation between MR spectroscopic parameters and fatigue scores (r ≤ 0.25 and P ≥ .10 for all). Conclusion Participants with PCC showed differences in τPCr and Qmax compared with healthy controls, suggesting potential mitochondrial dysfunction. This finding did not correlate with fatigue scores. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Parraga and Eddy in this issue.}, } @article {pmid39717873, year = {2025}, author = {Patel, AMR and Gilpin, G and Koniotes, A and Warren, C and Xu, C and Burgess, PW and Chan, D}, title = {Clinic evaluation of cognitive impairment in post-COVID syndrome: Performance on legacy pen-and-paper and new digital cognitive tests.}, journal = {Brain, behavior, & immunity - health}, volume = {43}, number = {}, pages = {100917}, pmid = {39717873}, issn = {2666-3546}, abstract = {BACKGROUND: Cognitive impairment, colloquially termed "brain fog", is one of the most prevalent manifestations of post-Covid syndrome and a major contributor to impaired daily function and reduced quality of life. However, despite the high numbers of affected individuals presenting to clinical services with cognitive impairment, little work has been undertaken to date on the suitability of current memory clinic tests for identifying the cognitive deficits in this new acquired cognitive disorder.The aim of this study was therefore to determine the performance of people with post-Covid syndrome presenting with cognitive impairment on the Addenbrooke's Cognitive Examination-III (ACE-III), a cognitive test used widely in memory clinics. A subset of individuals also underwent testing on a novel battery of short digital tests assessing attention, speed of information processing and executive function, representing the domains primarily implicated in post-Covid cognitive dysfunction.

METHODS: 102 individuals with post-Covid syndrome presenting with subjective cognitive complaints were recruited from a specialist cognitive long Covid clinic at University Hospitals Sussex NHS Trust. All participants completed self-report questionnaires on depression, anxiety, sleep and fatigue. Cognitive performance was assessed using the ACE-III, with 20 participants also being tested on the digital Long COVID Assessment Battery (LCCAB) (N = 20).

RESULTS: The overall sample had a mean ACE-III score of 91/100 (SD 6) with 15.7% (16/102) scoring at or below the cut-off score considered to represent objective cognitive impairment. Of the 20 individuals who also completed the LCCAB, 89.47% were impaired on at least one task, primarily in the domains of attention, executive function and processing speed. Cognitive performance was not associated with depression, anxiety, sleep quality or fatigue.

CONCLUSION: The vast majority of individuals with post-Covid syndrome presenting with subjective cognitive complaints do not exhibit impaired performance on the ACE-III. This likely reflects the historical use of ACE-III and other pen and paper cognitive tests to detect cognitive impairment in diseases causing dementia, but they are ill-equipped to identify impairment in those cognitive domains affected in post-Covid syndrome. The LCCAB detected cognitive impairments in nearly 90% of participants, primarily affecting attention, executive function, and processing speed. These observations highlight the need for alternative cognitive tests for use in routine clinical practice to detect the impairments in new acquired cognitive disorders that are not adequately captured by legacy tests.}, } @article {pmid39717862, year = {2025}, author = {Konishi, S and Masaki, K and Shimamoto, K and Ibuka, Y and Goto, R and Namkoong, H and Chubachi, S and Terai, H and Asakura, T and Miyata, J and Azekawa, S and Nakagawara, K and Tanaka, H and Morita, A and Harada, N and Sasano, H and Nakamura, A and Kusaka, Y and Ohba, T and Nakano, Y and Nishio, K and Nakajima, Y and Suzuki, S and Yoshida, S and Tateno, H and Fukunaga, K}, title = {The relationship between long COVID, labor productivity, and socioeconomic losses in Japan: A cohort study.}, journal = {IJID regions}, volume = {14}, number = {}, pages = {100495}, pmid = {39717862}, issn = {2772-7076}, abstract = {OBJECTIVES: We examined shifts in labor productivity and their economic ramifications among adult patients with long COVID in Japan.

METHODS: A total of 396 patients were categorized into three groups based on symptom progression: non-long COVID, long COVID recovered, and long COVID persistent. Patient-reported outcomes were assessed at three time intervals: 3, 6, and 12 months after COVID-19 diagnosis. Labor productivity was gauged through presenteeism and absenteeism, measured using the World Health Organization Health and Work Performance Questionnaire.

RESULTS: Long COVID was observed in 52.7% of patients, and 29.3% of all the patients continued to experience long COVID symptoms 1 year after diagnosis. At all three time points (3, 6, and 12 months after diagnosis), the long COVID persistent group showed a statistically significant difference in absolute presenteeism compared with the non-long COVID and long COVID recovered groups (P <0.01). Economic loss owing to decrease in labor productivity was calculated as $21,659 per year in the long COVID persistent group and $9008 per year in the long COVID recovered group (P <0.01).

CONCLUSION: The study's results revealed a notable decline in labor productivity over time, underscoring the importance of early detection and intervention to mitigate the socio-economic repercussions of long COVID, in addition to its health implications.}, } @article {pmid39717772, year = {2024}, author = {Vojdani, A and Yaqinuddin, A and Beretta, A and Reche, PA}, title = {Editorial: Cross-reactive immunity and COVID-19.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1509379}, pmid = {39717772}, issn = {1664-3224}, } @article {pmid39717543, year = {2024}, author = {Yi, J and Liu, Z and Cao, X and Pi, L and Zhou, C and Mu, H}, title = {Development of a prediction nomogram for IgG levels among asymptomatic or mild patients with COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1477585}, pmid = {39717543}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/immunology/diagnosis/blood ; *Nomograms ; *Immunoglobulin G/blood ; Male ; Female ; Middle Aged ; Retrospective Studies ; Adult ; *SARS-CoV-2/immunology ; *Interleukin-6/blood ; Aged ; Immunoglobulin M/blood ; ROC Curve ; Antibodies, Viral/blood ; Asymptomatic Infections ; Age Factors ; COVID-19 Vaccines/immunology ; Procalcitonin/blood ; }, abstract = {OBJECTIVE: COVID-19 has evolved into a seasonal coronavirus disease, characterized by prolonged infection duration and repeated infections, significantly increasing the risk of patients developing long COVID. Our research focused on the immune responses in asymptomatic and mild cases, particularly the critical factors influencing serum immunoglobulin G (IgG) levels and their predictive value.

METHODS: We conducted a retrospective analysis on data from 1939 asymptomatic or mildly symptomatic COVID-19 patients hospitalized between September 2022 and June 2023. Spearman methods were used to test the correlation between serum IgG and age, immunoglobulin M (IgM), procalcitonin (PCT), interleukin-6 (IL-6), nucleic acid conversion time, and BMI. Univariate and multivariate logistic regression analyses identified independent key factors influencing serum IgG levels, which were integrated and visualized in a nomogram. Finally, receiver operating characteristic (ROC) curves were plotted to predict the model's diagnostic performance by calculating the AUC.

RESULTS: Mild patients showed higher levels of IgG, IgM, and longer nucleic acid conversion times than asymptomatic patients, and a lower proportion of them had received ≥ 3 COVID-19 vaccine doses. Serum IgG was positively correlated with serum IgM and negatively correlated with age, PCT, IL-6, and BMI. Notably, it showed a moderate negative correlation with nucleic acid conversion time (r = -0.578, P < 0.001). Logistic regression results showed that younger age, lower IL-6 levels, ≥ 3 doses of vaccine, and no comorbidities were independent predictors of serum IgG levels ≥ 21.08 g/L. We used age, IL-6 levels, vaccine doses, and comorbidities to create a nomogram for predicting serum IgG levels, with the area under the ROC curve reaching 0.772.

CONCLUSION: Age, IL-6 levels, vaccination status, and comorbidities were independent predictors of serum IgG levels in asymptomatic or mild COVID-19 patients, facilitating risk stratification and clinical decision-making. Notably, receiving ≥3 doses of the COVID-19 vaccine was the most beneficial factor for elevated serum IgG levels.}, } @article {pmid39717071, year = {2024}, author = {Zambrano, K and Castillo, K and Peñaherrera, S and Vasconez, HC and Caicedo, A and Gavilanes, AWD}, title = {Understanding Post-COVID-19: Mechanisms, Neurological Complications, Current Treatments, and Emerging Therapies.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {6303-6321}, pmid = {39717071}, issn = {1178-7074}, abstract = {COVID-19, a highly infectious disease, caused a worldwide pandemic in early 2020. According to the World Health Organization (WHO), COVID-19 has resulted in approximately 774 million cases and around 7 million deaths. The effects of COVID-19 are well known; however, there is a lack of information on the pathophysiological mechanisms underlying the symptoms that comprise Post-Acute COVID-19 Syndrome (PACS) or Long COVID-19. Neurological sequelae are common, with cognitive dysfunction being one of the foremost symptoms. Research indicates that elevated inflammatory levels and increased oxidative stress may play a role in the etiology and severity of PACS. Treatment options are extremely limited, and there is no consensus among the medical and scientific communities on how to manage the disease. Nevertheless, many scientists advocate for using antioxidants for symptomatic therapy and cognitive behavior therapy for supportive care. Additionally, current research aims to ameliorate several aspects of the inflammatory cascade. This review highlights the intracellular and extracellular pathways crucial to the neurological manifestations of PACS, providing valuable information for healthcare professionals and scientists. Given the complex nature of PACS, understanding these pathways is essential for developing new treatment options. Assessing PACS is challenging, and reviewing current therapeutic options while proposing a triad of potential therapeutic elements will add value to clinical assays and guidelines. Current therapeutic strategies, such as antioxidants/vitamin supplements, neurogenic stem cell therapy, and mitochondrial therapy, could be combined to enhance their effectiveness. Future research should focus on validating these approaches and exploring new avenues for the effective treatment of PACS.}, } @article {pmid39715694, year = {2025}, author = {Cáceres, E and Divani, AA and Viñan-Garces, AE and Olivella-Gomez, J and Quintero-Altare, A and Pérez, S and Reyes, LF and Sasso, N and Biller, J}, title = {Tackling persistent neurological symptoms in patients following acute COVID-19 infection: an update of the literature.}, journal = {Expert review of neurotherapeutics}, volume = {25}, number = {1}, pages = {67-83}, doi = {10.1080/14737175.2024.2440543}, pmid = {39715694}, issn = {1744-8360}, mesh = {Humans ; *COVID-19/complications/therapy ; *Nervous System Diseases/therapy ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered. Researchers started to recognize those persisting symptoms as a new entity termed 'Long COVID,' where neurological symptoms are evident and have a major impact on quality of life.

AREAS COVERED: The main purpose of this narrative review is to analyze and synthesize the current literature regarding Long COVID, its relation to the nervous system, and to explore the evidence on treatments for persistent neurological symptoms. The most common reported and observed neurologic manifestations include fatigue, cognitive impairment, pain, polyneuropathy, and neuropsychiatric disorders. A variety of pharmacologic and non-pharmacologic therapies have been evaluated and yielded mixed results. Many of them focused on immunomodulation and none currently have U.S. FDA approval.

EXPERT OPINION: Challenges remain in terms of clinical characterization and prognosis of Long COVID, besides understanding its pathophysiology. Standardization of biomarkers and diagnostic criteria will allow the use of common nomenclature and data elements in the design of future clinical studies.}, } @article {pmid39713294, year = {2024}, author = {Oliveira, KX and Suzuki, YJ}, title = {Angiotensin peptides enhance SARS-CoV-2 spike protein binding to its host cell receptors.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.12.628247}, pmid = {39713294}, issn = {2692-8205}, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that caused the Coronavirus Disease 2019 (COVID-19) pandemic, has a spike glycoprotein that is involved in recognizing and fusing to host cell receptors, such as angiotensin-converting enzyme 2 (ACE2), neuropilin-1 (NRP1), and AXL tyrosine-protein kinase. Since the major spike protein receptor is ACE2, an enzyme that regulates angiotensin II (1-8), this study tested the hypothesis that angiotensin II (1-8) influences the binding of the spike protein to its receptors. While angiotensin II (1-8) did not influence spike-ACE2 binding, we found that it significantly enhances spike-AXL binding. Our experiments showed that longer lengths of angiotensin, such as angiotensin I (1-10), did not significantly affect spike-AXL binding. In contrast, shorter lengths of angiotensin peptides, in particular, angiotensin IV (3-8), strongly increased spike-AXL binding. Angiotensin IV (3-8) also enhanced spike protein binding to ACE2 and NRP1. The discovery of the enhancing effects of angiotensin peptides on spike-host cell receptor binding may suggest that these peptides could be pharmacological targets to treat COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), which is also known as long COVID.}, } @article {pmid39713288, year = {2024}, author = {Comba, IY and Mars, RAT and Yang, L and Dumais, M and Chen, J and Van Gorp, TM and Harrington, JJ and Sinnwell, JP and Johnson, S and Holland, LA and Khan, AK and Lim, ES and Aakre, C and Athreya, AP and Gerber, GK and O'Horo, JC and Lazaridis, KN and Kashyap, PC}, title = {Gut Microbiome Signatures During Acute Infection Predict Long COVID.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.10.626852}, pmid = {39713288}, issn = {2692-8205}, abstract = {Long COVID (LC), manifests in 10-30% of non-hospitalized individuals post-SARS-CoV-2 infection leading to significant morbidity. The predictive role of gut microbiome composition during acute infection in the development of LC is not well understood, partly due to the heterogeneous nature of disease. We conducted a longitudinal study of 799 outpatients tested for SARS-CoV-2 (380 positive, 419 negative) and found that individuals who later developed LC harbored distinct gut microbiome compositions during acute infection, compared with both SARS-CoV-2-positive individuals who did not develop LC and negative controls with similar symptomatology. However, the temporal changes in gut microbiome composition between the infectious (0-1 month) and post-infectious (1-2 months) phases was not different between study groups. Using machine learning, we showed that microbiome composition alone more accurately predicted LC than clinical variables. Including clinical data only marginally enhanced this prediction, suggesting that microbiome profiles during acute infection may reflect underlying health status and immune responses thus, help predicting individuals at risk for LC. Finally, we identified four LC symptom clusters, with gastrointestinal and fatigue-only groups most strongly linked to gut microbiome alterations.}, } @article {pmid39712068, year = {2024}, author = {Hultgren, NW and Petcherski, A and Torriano, S and Komirisetty, R and Sharma, M and Zhou, T and Burgess, BL and Ngo, J and Osto, C and Shabane, B and Shirihai, OS and Kelesidis, T and Williams, DS}, title = {Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences.}, journal = {PNAS nexus}, volume = {3}, number = {12}, pages = {pgae500}, pmid = {39712068}, issn = {2752-6542}, abstract = {As the SARS-CoV-2 coronavirus continues to evolve and infect the global population, many individuals are likely to suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Manifestations of PASC include vision symptoms, but little is known about the ability of SARS-CoV-2 to infect and impact the retinal cells. Here, we demonstrate that SARS-CoV-2 can infect and perturb the retinal pigment epithelium (RPE) in vivo, after intranasal inoculation of a transgenic mouse model of SARS-CoV-2 infection, and in cell culture. Separate lentiviral studies showed that SARS-CoV-2 Spike protein mediates viral entry and replication in RPE cells, while the Envelope and ORF3a proteins induce morphological changes. Infection with major variants of SARS-CoV-2 compromised the RPE barrier function and phagocytic capacity. It also caused complement activation and production of cytokines and chemokines, resulting in an inflammatory response that spread across the RPE layer. This inflammatory signature has similarities to that associated with the onset of age-related macular degeneration (AMD), a major cause of human blindness, resulting from RPE pathology that eventually leads to photoreceptor cell loss. Thus, our findings suggest that post-acute sequelae of SARS-CoV-2 infection of the RPE may have long-term implications for vision, perhaps comparable to the increased occurrence of AMD found among individuals infected by HIV, but with greater public health consequences due to the much larger number of SARS-CoV-2 infections.}, } @article {pmid39711472, year = {2024}, author = {Thompson, CM and Gerlikovski, E and Babu, S and McGuire, M and Robieson, I and Ranallo, A}, title = {A Longitudinal Interview Study of People with Long COVID: Uncertainties, Liminality, and Processes of Becoming.}, journal = {Health communication}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/10410236.2024.2442684}, pmid = {39711472}, issn = {1532-7027}, abstract = {Current estimates indicate around 6% of US adults have experienced long COVID symptoms. Given the novelty of both COVID and long COVID, those who continue to be ill after an initial SARS-CoV-2 infection have little precedence on which to rely when navigating the medical (e.g. diagnoses, treatment options), social (e.g. others' reactions, isolation), and personal (e.g. roles, identities) sources of uncertainty that accompany the illness. In this study, we explore uncertainty as a process of liminality, a heuristically useful lens for demonstrating how uncertainties intertwine, compound, contradict, and change across time, and how people are continually in a process of "becoming." We interviewed 19 people with long COVID five times during the middle stages of the pandemic (Summer 2021 to Summer 2022; 89 total interviews). Findings illustrate how liminality is a body-self dialectic characterized by physical changes that bear upon valued identities and how this dialectic is shaped by a sociocultural and historical context comprising medical, social, political, and mediated spheres of life. We discuss the contributions of this research for theorizing about uncertainty, conducting longitudinal qualitative research, and living with chronic illness.}, } @article {pmid39711218, year = {2024}, author = {Rohn, H and Elischer, F and Larbig, L and Jansen, S and Schramm, S and Otte, M and Konik, M and Paniskaki, K and Weber, P and Reinold, J and Gäckler, A and Krawczyk, A and Wilde, B and Trilling, M and Michita, RT and Möhlendick, B and Siffert, W and Brenner, T and Dinse, H and Skoda, EM and Horn, PA and Witzke, O and Rebmann, V}, title = {Influence of HLA-G 3' Untranslated Region Haplotypes and SNP +3422 Gene Variants as Host Genetic Factors on the Outcomes of SARS-CoV-2 Infection During Acute and Post-Acute Phases in a German Cohort.}, journal = {HLA}, volume = {104}, number = {6}, pages = {e15799}, pmid = {39711218}, issn = {2059-2310}, support = {//Rudolf Ackermann Foundation/ ; 422744262-TRR289//Deutsche Forschungsgemeinschaft DFG Projektnummer/ ; //Gilead Science Grant/ ; //Ministerium für Kultur und Wissenschaft des Landes NRW/ ; //Stiftung Universitätsmedizin Essen/ ; }, mesh = {Humans ; *COVID-19/genetics/immunology/virology ; *3' Untranslated Regions ; *Haplotypes ; *SARS-CoV-2/immunology ; *Polymorphism, Single Nucleotide ; *HLA-G Antigens/genetics ; Male ; Female ; Middle Aged ; Germany ; Aged ; Cohort Studies ; Adult ; Genetic Predisposition to Disease ; Prognosis ; }, abstract = {HLA-G, an important immune-checkpoint (IC) molecule that exerts inhibitory signalling on immune effector cells, has been suggested to represent a key player in regulating the immune response to Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2). Since specific single-nucleotide polymorphisms (SNP) in the HLA-G 3'untranslated region (UTR), which arrange as haplotypes, are crucial for the regulation of HLA-G expression, we analysed the contribution of these genetic variants as host factors in SARS-CoV-2 infection during acute and post-acute phases. HLA-G gene polymorphisms in the 3'UTR were investigated by sequencing in an unvaccinated Coronavirus Disease 2019 (COVID-19) cohort during acute SARS-CoV-2 infection (N = 505) and in the post-acute phase (N = 253). The HLA-G 3'UTR haplotype known as UTR-3 (p = 0.002) and the variant rs17875408 (also known as +3422) T variant (p = 0.004) are independent prognostic risk factors for fatal COVID-19. The +3422T variant (p = 0.006) predicted also the early loss of neutralising SARS-CoV-2 antibodies. In addition, the HLA-G 3'UTR haplotype UTR-7 (p = 0.023) emerged as an independent prognostic factor for increased susceptibility to Long-COVID symptoms after SARS-CoV-2 infection. Our study highlights that due to the variability of the 3'UTR genetic background, HLA-G has the potential to contribute to the progression of SARS-CoV-2 infection, extending to the development of Long-COVID symptoms, despite the likely alterations in the microenvironment and associated HLA-G-specific regulatory elements over the course of the disease. By spotlighting HLA-G, the importance of the genetic background of IC and their pivotal role in modulating immune responses during and after COVID-19 are emphasised.}, } @article {pmid39710927, year = {2024}, author = {Heidari, F and Farahighasreaboonasr, F and Mohammad Hassan, Z and Fazeli, P and Hosseini, M and Ebtekar, M}, title = {Annual SZ: An Alternative Immunotherapy for COVID-19 and Long COVID.}, journal = {Infectious disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715265323116241104052004}, pmid = {39710927}, issn = {2212-3989}, abstract = {Since the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 and early 2020, the identification of drugs to control severe acute respiratory syndrome coro-navirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing focus of research. Cytokine storm and acute respiratory distress syndrome (ARDS) are the leading causes of mortality following infection. In this review, we discuss immune pathogenesis and four medications, including Remdesivir, Tocilizumab, Dexamethasone, and Annual SZ for COVID-19. A comparison of the effectiveness and therapeutic usage of drugs as reported in clinical trials and reports was made at different disease levels as well. Clinical studies indicate that Annual SZ with mild side effects was more affordable and might be more effective than other medications. Additionally, Annual SZ was capable of reducing the lev-els of pro-inflammatory cytokines as well as viral attachment and RNA replication.}, } @article {pmid39710703, year = {2024}, author = {Duncan, A and Veli, I and Tsosie, D and Koffler, E}, title = {Probable collagenous gastritis via Epstein-Barr virus reactivation in the setting of coronavirus disease 2019: a case report.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {605}, pmid = {39710703}, issn = {1752-1947}, mesh = {Humans ; Male ; Middle Aged ; *COVID-19/complications ; *Epstein-Barr Virus Infections/complications/drug therapy/diagnosis ; *Gastritis/virology/drug therapy ; *Herpesvirus 4, Human ; SARS-CoV-2 ; *Virus Activation ; }, abstract = {BACKGROUND: Recent biomedical research has shown the unusual, multisystem effects of coronavirus disease 2019 in humans. One specific sequela of a primary severe acute respiratory syndrome coronavirus 2 infection is the reactivation of latent viruses in various tissues, such as Epstein-Barr virus. Epstein-Barr virus has been identified in many inflammatory gastrointestinal lesions, such as microscopic gastritides and colitides. One subtype of these diseases is collagenous disease. "Long COVID" may be related to the reactivation of these latent viruses, and the following case describes a patient who developed vague symptoms consistent with "long COVID."

CASE PRESENTATION: A non-Hispanic white male in his 50s, with previous collagenous gastritis and colitis, developed a 10-kg weight loss and diffuse leg cramps over 3 months. The patient had coronavirus disease 2019 about 3 months prior to presentation. He had iron deficiency and tested positive for human immunodeficiency virus antibody. His heterophile antibody was also positive. Confirmatory testing for human immunodeficiency virus was negative, and his Epstein-Barr virus antibody panel was positive for early antigen immunoglobulin G. His Epstein-Barr virus viral load was undetectable. Minimal improvement was achieved with a 4-week course of oral budesonide, and upper endoscopy showed diffuse gastritis. He is now improving with proton pump inhibitor therapy and ferrous sulfate supplementation.

CONCLUSION: This case report explores outpatient management of microscopic gastritides and colitides. The evidence around coronavirus disease 2019 causing reactivation of Epstein-Barr virus, and Epstein-Barr virus' presence in chronic gastrointestinal inflammatory lesions, is discussed. Practice recommendations include corticosteroid and acid-suppression therapy for patients suspected of having a recurrence of inflammatory lesions.}, } @article {pmid39710280, year = {2024}, author = {Brown, SA and Holland, J and Gaynor, K and Bramham, J and O'Keeffe, F and O'Flanagan, S and Savinelli, S and Mallon, P and Feeney, E and Kenny, G and McCann, K and Boyd, C}, title = {A psychological model of predictive factors of distress following long COVID.}, journal = {Journal of affective disorders}, volume = {373}, number = {}, pages = {394-402}, doi = {10.1016/j.jad.2024.12.049}, pmid = {39710280}, issn = {1573-2517}, abstract = {BACKGROUND: Long COVID, described as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection", is estimated to affect at least 10-20 % of all cases of acute SARS-CoV-2 infection. Because of its novelty, information regarding the experience of Long COVID is still emerging.

METHODS: This study examines psychological distress in two long COVID populations, and their experience of fatigue, cognitive failures, experiential avoidance, rumination, and perceived injustice. Participants were recruited via a long COVID hospital clinic and online self-diagnosing samples. Participants completed a battery of scales to measure psychological distress, fatigue, cognitive dysfunction, avoidance and rumination behaviours and the experience of injustice.

RESULTS: It was found that the regression model tested accounted for a significant amount of the variance in psychological distress (R[2] = 0.675). Cognitive failures, avoidance, rumination, and injustice experiences significantly contributed to the experience of psychological distress and a moderated mediation accounted for the effect of fatigue on psychological distress.

LIMITATIONS: The self-report measures in this study did not include objective measures of symptom severity. Cross-sectional data collected at a single time-point may not capture the dynamic nature of long COVID symptoms.

CONCLUSIONS: These findings identify contributing factors to the experience of psychological distress in the long COVID population, providing direction to explore supportive interventions.}, } @article {pmid39709886, year = {2024}, author = {Kohn, ER and Bohlke, M and Almeida, A and Janelli, L and Sardinha, LMV and Wehrmeister, FC and Hallal, PC}, title = {A post-pandemic snapshot of the magnitude of COVID-19 in Brazil: A countrywide study.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {29}, number = {1}, pages = {104496}, doi = {10.1016/j.bjid.2024.104496}, pmid = {39709886}, issn = {1678-4391}, abstract = {OBJECTIVE: To outline the features of COVID-19 in Brazil through a countrywide telephone survey.

METHODS: Data from the Telephone Survey of Risk Factors for Chronic Noncommunicable Diseases During the Pandemic (Covitel), a telephone survey of individuals aged 18 years or older from all macro-regions of Brazil, were used. The questionnaire included sociodemographic characteristics and outcomes related to COVID-19 infection, severity, vaccination, and use of masks.

RESULTS: Data revealed that 34.7 % (95 %CI 32.4 - 37.1) of the population had been diagnosed with COVID-19, and 10.1 % (95 %CI 7.9 - 12.7) of those required hospital admission. The prevalence of COVID-19 diagnosis increased with education level: <8 years (26.6 % [95 %CI 23.1 - 30.7]), 9-11 years (33.4 % [95 %CI 29.4 - 37.7]), and >11 years (53.2 % [95 % CI 49.7 - 56.8]). Nevertheless, the hospitalization rate of Brazilians with more than eleven years of education was lower (5.8 % [95 %CI 4.3 - 7.6]). In 2023, 92.9 % (95 %CI 90.9 - 94.4) of the Brazilian population was fully vaccinated against COVID-19, but only 37.2 % (95 %CI 33.5 - 40.9) have received the updated vaccinal scheme (two doses and two boosters). During the pandemic outbreak, 81.9 % (95 %CI 79.4 - 84.2) reported always using face masks. However, only 16.1 % (95 %CI 13.5 - 19.0) maintained this practice in 2023.

CONCLUSION: There were inequalities in COVID-19 testing in Brazil. Testing and vaccination policies implemented in the COVID-19 pandemic must be reevaluated by the Brazilian government.}, } @article {pmid39709062, year = {2024}, author = {McNeill, R and Marshall, R and Fernando, SA and Harrison, O and Machado, L}, title = {COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students.}, journal = {Brain, behavior, and immunity}, volume = {125}, number = {}, pages = {58-67}, doi = {10.1016/j.bbi.2024.12.002}, pmid = {39709062}, issn = {1090-2139}, abstract = {To date, 770 million people worldwide have contracted COVID-19, with many reporting long-term "brain fog". Concerningly, young adults are both overrepresented in COVID-19 infection rates and may be especially vulnerable to prolonged cognitive impairments following infection. This calls for focused research on this population to better understand the mechanisms underlying cognitive impairment post-COVID-19. Addressing gaps in the literature, the current study investigated differences in neuropsychological performance and cerebral haemodynamic activity following COVID-19 infection in undergraduate students. 94 undergraduates (age in years: M = 20.58, SD = 3.33, range = 18 to 46; 89 % female) at the University of Otago reported their COVID-19 infection history before completing a neuropsychological battery while wearing a multichannel near-infrared spectroscopy (NIRS) device to record prefrontal haemodynamics. We observed that 40 % retrospectively self-reported cognitive impairment (brain fog) due to COVID-19 and 37 % exhibited objective evidence of cognitive impairment (assessed via computerised testing), with some suggestion that executive functioning may have been particularly affected; however, group-level analyses indicated preserved cognitive performance post COVID-19, which may in part reflect varying compensatory abilities. The NIRS data revealed novel evidence that previously infected students exhibited distinct prefrontal haemodynamic patterns during cognitive engagement, reminiscent of those observed in adults four decades older, and this appeared to be especially true if they reported experiencing brain fog due to COVID-19. These results provide new insights into the potential neuropathogenic mechanisms influencing cognitive impairment following COVID-19.}, } @article {pmid39707582, year = {2024}, author = {Yusoff, HM and Mohamed, NC and Yew, SQ and Nawi, AM and Rashidah Ismail, OH and Tohit, NM and Mohamed, Z and Noordin, MAM and Mohd, FH and Shariff, MIA and Shaharum, MH and Rahman, AA and Dapari, R}, title = {Prevalence and risk factors of long covid and its associated adverse work outcomes among workers in the manufacturing sector in Malaysia - a mixed-methods study protocol.}, journal = {Journal of health, population, and nutrition}, volume = {43}, number = {1}, pages = {194}, pmid = {39707582}, issn = {2072-1315}, support = {UKMP-S230424//National Institute of Occupational Safety and Health (NIOSH) Malaysia/ ; }, mesh = {Humans ; Malaysia/epidemiology ; *COVID-19/epidemiology ; Risk Factors ; Prevalence ; SARS-CoV-2 ; Female ; Focus Groups ; Male ; Manufacturing Industry ; Surveys and Questionnaires ; Adult ; Work Performance ; Quality of Life ; }, abstract = {BACKGROUND: The manufacturing sector in Malaysia has been severely impacted by the COVID-19 pandemic. This is further exacerbated by Long COVID-19 symptoms among the manufacturing workers, which are proven to influence work performance and quality of life. Of note, there is currently a lack of knowledge regarding the burden of Long COVID-19 in the Malaysian manufacturing sector. As such, our study aims to investigate the prevalence and risk factors of Long COVID-19 symptoms among the manufacturing workers, and subsequently assess the prevalence and risk factors of adverse work outcomes among the workers with Long Covid-19 symptoms.

METHODS: This is an exploratory mixed-methods study. In phase 1 (qualitative phase), three groups of participants (i.e., clinicians, employers, and workers) will be invited to participate to focus group discussions (FGDs) until thematic saturation. The aim of the FGDs is to explore the understanding, experience, and potential risk factors of Long Covid-19 among manufacturing workers. Findings from the FGDs will be analysed thematically. Themes generated from the FGDs will be used to generate items in a new questionnaire. The newly developed questionnaire will be validated using a fuzzy Delphi study, which will also be conducted among clinicians, employers, and workers. Phase 2 is a cross-sectional study that will be conducted among manufacturing workers across all states in Malaysia to identify the prevalence and risk factors of Long COVID-19, as well as the prevalence and risk factors of adverse work outcomes among workers with Long COVID-19. A multistage cluster sampling will be used to collect data from 4500 manufacturing workers in Malaysia. Logistic regression will be performed to determine the association between risk factors with both Long COVID-19 and adverse work outcomes.

CONCLUSION: Once the prevalence and risk factors of Long COVID and its associated adverse work outcome are identified, timely support and effective interventions could be provided to manufacturing workers to maintain their health and productivity.

ETHICAL CONSIDERATIONS: Ethical approval has been granted by the Research Ethics Committee of the National University of Malaysia (JEP-2023-607) and the Medical Research and Ethics Committee (MREC) Malaysia (NMRR ID-23-03310-H3E).}, } @article {pmid39707044, year = {2024}, author = {Schlegtendal, A and Maier, C and Stein, J and Höpner, J and Petersmann, A and Drinka, D and Berner, R and Lücke, T and Toepfner, N and Brinkmann, F}, title = {Post-coronavirus disease 2019-associated symptoms among children and adolescents in the SARS-CoV-2 Omicron era.}, journal = {European journal of pediatrics}, volume = {184}, number = {1}, pages = {96}, pmid = {39707044}, issn = {1432-1076}, support = {BMBF 01KX2121//German Federal Ministry of Education and Research/ ; }, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/complications ; Child ; Adolescent ; Male ; Female ; Cross-Sectional Studies ; *Quality of Life ; Child, Preschool ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Germany/epidemiology ; Cohort Studies ; Case-Control Studies ; }, abstract = {PURPOSE: Lack of a control group(s) and selection bias were the main criticisms of previous studies investigating the prevalence of post-coronavirus disease 2019 (COVID-19) syndrome (PCS). There are insufficient data regarding paediatric PCS, particularly in the SARS-CoV-2 Omicron era. As such, our study investigated PCS-associated symptoms in a representative control-matched cohort.

METHODS: This multicentre, cross-sectional, cohort study within the "Immunebridge" project of the German Network University Medicine (NUM) recruited children and adolescents (five to 17 years old) between July and October 2022. Children with polymerase chain reaction-confirmed SARS-CoV-2 infection in 2022 (COVID-19 group) were compared with those without history of SARS-CoV-2 infection and negative for SARS-CoV-2 antibodies. Queries included vaccinations, quality of life (QoL), and mental and physical symptoms potentially associated with PCS in the previous three months. An additional composite item, "physical performance", was created from the responses.

RESULTS: The number of children with ≥ 1 PCS symptom(s) was comparable between the COVID-19 (n = 114 [62.1%]) and control (n = 66 [64.9%]) groups. Concentration disorders were reported more frequently in the COVID-19 group (12.3% versus 1.5%; p = 0.012) and "physical performance" was significantly impaired (p = 0.016) regardless of age, sex, and SARS-CoV-2 vaccination. The frequencies of other symptoms were similar in both groups. The COVID-19 group rated their fitness as worse, with otherwise equal QoL ratings regarding general and mental health. Conclusion Children with and without previous infections did not differ in most PCS-associated symptoms. Exceptions included physical performance and cognitive problems, which appeared to be more impaired after Omicron infection than in controls.

WHAT IS KNOWN: • Mainly due to too few controlled studies, knowledge about the prevalence of individual symptoms in paediatric post-COVID-19 syndrome (PCS) for the Omicron era is poor.

WHAT IS NEW: • In a representative control-matched cohort most parent-reported PCS-associated symptoms and quality of life scores in children and adolescents with PCR-confirmed SARS-CoV-2 infection did not differ from those without infection. • Exceptions were physical performance and cognitive problems, which were apparently more severely impaired after SARS-CoV-2-Omicron infection than in the control subjects.}, } @article {pmid39706670, year = {2025}, author = {Hayes, LD}, title = {Introduction to the Long COVID Mechanisms, Risk Factors, and Recovery: From Cells to Society.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {87}, doi = {10.1016/j.amjmed.2024.11.001}, pmid = {39706670}, issn = {1555-7162}, } @article {pmid39706056, year = {2025}, author = {Culiat, C and Soni, D and Malkes, W and Wienhold, M and Zhang, LH and Henry, E and Dragan, M and Kar, S and Angeles, DM and Eaker, S and Biswas, R}, title = {NELL1 variant protein (NV1) modulates hyper-inflammation, Th-1 mediated immune response, and the HIF-1α hypoxia pathway to promote healing in viral-induced lung injury.}, journal = {Biochemical and biophysical research communications}, volume = {744}, number = {}, pages = {151198}, doi = {10.1016/j.bbrc.2024.151198}, pmid = {39706056}, issn = {1090-2104}, mesh = {*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Humans ; Animals ; *Lung Injury/immunology/virology/pathology/metabolism ; Th1 Cells/immunology ; Inflammation/metabolism/immunology ; COVID-19/immunology/virology/metabolism ; Calcium-Binding Proteins/metabolism/genetics ; Mice ; Signal Transduction ; Cytokines/metabolism/immunology ; SARS-CoV-2/immunology ; Wound Healing ; Mice, Inbred C57BL ; }, abstract = {Research underscores the urgent need for technological innovations to treat lung tissue damage from viral infections and the lasting impact of COVID-19. Our study demonstrates the effectiveness of recombinant human NV1 protein in promoting a pro-healing extracellular matrix that regulates homeostasis in response to excessive tissue reactions caused by infection and injury. NV1 achieves this by calibrating multiple biological mechanisms, including reducing hyperinflammatory cytokine levels (e.g., IFN-γ, TNF-α, IL-10, and IP-10), enhancing the production of proteins involved in viral inactivation and clearance through endocytosis and phagocytosis (e.g., IL-9, IL-1α), regulating pro-clotting and thrombolytic pathways (e.g., downregulates SERPINE 1 and I-TAC during Th1-mediated inflammation), maintaining cell survival under hypoxic conditions via HIF-1α regulation through the M3K5-JNK-AP-1 and TSC2-mTOR pathways, and promoting blood vessel formation. Our findings reveal NV1 as a potential therapeutic candidate for treating severe lung injuries caused by inflammatory and hypoxic conditions from viral infections and related diseases.}, } @article {pmid39705503, year = {2024}, author = {Konkle, SL and Magleby, R and Bonacci, RA and Segaloff, HE and Dimitrov, LV and Mahale, P and Katic, B and Nji, M and Cadwell, B and Ko, JY and Bushman, D and Rushmore, J and Cope, J and Saydah, S}, title = {Post-COVID Condition Risk Factors and Symptom Clusters and Associations with Return to Pre-COVID Health-Results from a 2021 Multi-State Survey.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciae632}, pmid = {39705503}, issn = {1537-6591}, abstract = {BACKGROUND: Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual's return to pre-COVID health.

METHODS: We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual's return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March-December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters.

FINDINGS: Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March-December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8-60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health.

INTERPRETATION: Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.}, } @article {pmid39705022, year = {2024}, author = {Anderer, S}, title = {Women's Immune Systems May Explain Increased Long COVID Diagnoses.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2024.25505}, pmid = {39705022}, issn = {1538-3598}, } @article {pmid39704834, year = {2024}, author = {Smadja, DM and Günther, S and Cavagna, P and Renaud, B and Salmon, D and Hermann, B and Ranque, B and Lemogne, C and Diehl, JL and Philippe, A}, title = {Circulating endothelial cells: a key biomarker of persistent fatigue after hospitalization for COVID-19.}, journal = {Angiogenesis}, volume = {28}, number = {1}, pages = {8}, pmid = {39704834}, issn = {1573-7209}, } @article {pmid39704047, year = {2024}, author = {Krishna, B and Metaxaki, M and Perera, M and Wills, M and Sithole, N}, title = {Comparison of different T cell assays for the retrospective determination of SARS-CoV-2 infection.}, journal = {The Journal of general virology}, volume = {105}, number = {12}, pages = {}, doi = {10.1099/jgv.0.002055}, pmid = {39704047}, issn = {1465-2099}, mesh = {Humans ; *COVID-19/diagnosis/immunology/virology ; *SARS-CoV-2/immunology ; *Sensitivity and Specificity ; Retrospective Studies ; *T-Lymphocytes/immunology ; Enzyme-Linked Immunosorbent Assay/methods ; Antibodies, Viral/blood/immunology ; Memory T Cells/immunology ; }, abstract = {It is important to be able to retrospectively determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections with high accuracy, both for post-coronavirus disease 2019 (COVID-19) epidemiological studies, and to distinguish between Long COVID and other multi-syndromic diseases that have overlapping symptoms. Although serum antibody levels can be measured to retrospectively diagnose SARS-CoV-2 infections, peptide stimulation of memory T cell responses is a more sensitive approach. This is because robust memory T cells are generated after SARS-CoV-2 infection and persist even after antibodies wane below detectability thresholds. In this study, we compare T cell responses using FluoroSpot-based methods and overnight stimulation of whole blood with SARS-CoV-2 peptides followed by an ELISA. Both approaches have comparable sensitivity and specificity but require different equipment and samples to be used. Furthermore, the elimination of peptides that cross-react with other coronaviruses increases the assay specificity but trades off some sensitivity. Finally, this approach can be used on archival, cryopreserved PBMCs. This work shows comparative advantages for several methods to measure SARS-CoV-2 T cell responses that could be utilized by any laboratory studying the effects of the coronavirus disease 2019 pandemic.}, } @article {pmid39703612, year = {2024}, author = {Mathew, J and Nugent, K}, title = {Post-Acute Sequelae of SARS-CoV-2 Infections: Exercise Limitation and Rehabilitation.}, journal = {The Yale journal of biology and medicine}, volume = {97}, number = {4}, pages = {463-472}, pmid = {39703612}, issn = {1551-4056}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Exercise/physiology ; Exercise Tolerance/physiology ; Exercise Therapy/methods ; }, abstract = {Patients with prior SARS-CoV-2 infections can develop chronic symptoms; this clinical presentation has been called post-acute sequelae of SARS-CoV-2 infection, post-COVID condition, and long COVID. It can develop in both outpatient cases and in hospital cases; the frequency depends on the severity of infection and comorbidity. Many of these patients have exercise limitation when tested using cardiopulmonary exercise tests. The potential explanations for reduced exercise capacity include cardiac limitations, respiratory limitations, skeletal muscle weakness, deconditioning, and limiting symptoms out of proportion to any measured physiological limitation, and many patients have more than one explanation for the exercise limitation. Since these patients may have required prolonged hospitalization, deconditioning has been considered a potential explanation for their post-hospitalization limitations. Patients with deconditioning have a low oxygen uptake per minute (VO2) maximum with no obvious cardiac or respiratory limitation, but some do have measurable muscle weakness. One complex study reported that these patients had a high proportion of high-fatigable glycolytic fibers, reduced mitochondrial function, atrophic fibers, and focal necrosis in skeletal muscle. Some post-COVID patients have chronic fatigue and post-exertional malaise and meet the clinical criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Most patients with post-COVID syndrome do improve with conventional cardiopulmonary rehabilitation. However, patients with post-exertional malaise need special attention to their exercise programs and careful monitoring for adverse effects. In summary, patients with long COVID can have complex presentations with a broad range of symptoms and several possible exercise limitations. Their rehabilitation program should be based on their physical capacity and their symptom profile.}, } @article {pmid39703608, year = {2024}, author = {Zollner, A and Meyer, M and Jukic, A and Adolph, T and Tilg, H}, title = {The Intestine in Acute and Long COVID: Pathophysiological Insights and Key Lessons.}, journal = {The Yale journal of biology and medicine}, volume = {97}, number = {4}, pages = {447-462}, pmid = {39703608}, issn = {1551-4056}, mesh = {Humans ; *COVID-19/physiopathology/virology/immunology ; *Gastrointestinal Microbiome/physiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Brain-Gut Axis/physiology ; Intestines/virology/physiopathology/microbiology ; }, abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.}, } @article {pmid39703524, year = {2024}, author = {Fernández-Pedruelo, D and Juárez-Vela, R and Ruiz de Viñaspre-Hernández, R and Alonso-Alonso, J and Criado-Gutiérrez, JM and Sancho-Sánchez, C}, title = {Influence of smoking and obesity on post-COVID-19 sequelae and risk of hospitalization.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1499239}, pmid = {39703524}, issn = {2296-858X}, abstract = {INTRODUCTION: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted the global healthcare system, with particularly harmful effects on the human respiratory system. Beyond the acute symptoms, there is growing concern about persistent symptoms that last for weeks or months after the initial infection, known as long COVID syndrome. This study focuses on investigating the relationship between smoking, obesity, and the presence of post-COVID-19 sequelae, as well as their influence on the risk of hospitalization.

MATERIALS AND METHODS: An observational and retrospective study was conducted using medical records of patients diagnosed with COVID-19 in Castilla y León, Spain, between November 1 and 30, 2020. The patients were divided into three groups: smoking (current and former), obesity/overweight, and control group. Various variables were analyzed, including age, sex, and the presence of post-COVID-19 sequelae, chronic pathologies, cardiovascular diseases, psychological conditions, and hospitalization. Descriptive statistics and Odds Ratio analysis were used for comparisons.

RESULTS: The results revealed that obesity was significantly associated with a higher risk of post-COVID-19 sequelae, particularly memory disorders and neurological, mental, or psychological symptoms. In contrast, smoking was correlated with an increase in memory problems but did not show a direct influence on post-COVID-19 sequelae or hospitalization. Additionally, women were found to have a higher prevalence of obesity in the studied population.

CONCLUSION: This study provides evidence that obesity increases the risk of post-COVID-19 sequelae, especially in terms of memory disorders and neuropsychological symptoms. On the other hand, smoking is related to memory problems. Regarding cardiovascular pathologies, there was not enough statistical evidence for analysis, while for hospitalization, it was determined that smoking and obesity do not have a direct influence on these post-COVID consequences.}, } @article {pmid39702051, year = {2024}, author = {Avinir, A and Kupershmidt, A and Amsterdam, D and Choshen, G and Ablin, JN and Elkana, O}, title = {Personality and neuropsychiatric symptoms in individuals diagnosed with long COVID.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1449}, pmid = {39702051}, issn = {1471-2334}, mesh = {Humans ; Female ; Male ; *COVID-19/psychology/complications ; Middle Aged ; *Cognitive Dysfunction ; *Personality ; Aged ; Surveys and Questionnaires ; Adult ; Neuroticism ; Sleep Wake Disorders/epidemiology ; SARS-CoV-2 ; Psychological Distress ; Post-Acute COVID-19 Syndrome ; Anxiety Disorders/psychology ; Social Support ; }, abstract = {OBJECTIVE: This study investigates persistent physical and neuropsychiatric symptoms in Long COVID, focusing on their severity and assessing risk/resilience factors, including conscientiousness and neuroticism. The study utilizes a mediation model to explore the potential role of psychological distress in mediating its impact on cognitive decline.

METHODS: In an online survey, 114 participants diagnosed with Long COVID completed assessments, including the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) for psychological distress, Subjective Cognitive Decline (SCD) questionnaire for cognitive decline, Pittsburgh Sleep Quality Index (PSQI) for sleep disorders, and Multidimensional Scale of Perceived Social Support (MSPSS) with "BIG-5 inventory" subscales for risk/resilience factors.

RESULTS: Findings showed high rates of depressive disorders (45.6%), generalized anxiety disorders (21%), sleep disturbances (76.3%), and reported cognitive changes (94.7%). Conscientiousness negatively correlated with psychological distress (p < .001, r = - .48) and cognitive decline (p < .001, r = - .36), while neuroticism positively correlated (p < .001, r = .62 and p < .001, r = .41, respectively). Social support negatively correlated with psychological distress (p < .001, r = - .52) and cognitive decline (p < .001, r = - .41). Psychological distress fully mediated personality traits and cognitive decline correlations, with significant full mediation for neuroticism [95% CI = (0.22, 0.48)] and conscientiousness [95% CI = (-0.33, -0.07)], controlling for age, gender, other chronic morbidity and social support.

CONCLUSION: The study underscores the significance of incorporating psychological interventions into treatment plans to alleviate distress symptoms associated with cognitive decline in conditions like Long COVID.}, } @article {pmid39701919, year = {2025}, author = {Alderman, JE and Palmer, J and Laws, E and McCradden, MD and Ordish, J and Ghassemi, M and Pfohl, SR and Rostamzadeh, N and Cole-Lewis, H and Glocker, B and Calvert, M and Pollard, TJ and Gill, J and Gath, J and Adebajo, A and Beng, J and Leung, CH and Kuku, S and Farmer, LA and Matin, RN and Mateen, BA and McKay, F and Heller, K and Karthikesalingam, A and Treanor, D and Mackintosh, M and Oakden-Rayner, L and Pearson, R and Manrai, AK and Myles, P and Kumuthini, J and Kapacee, Z and Sebire, NJ and Nazer, LH and Seah, J and Akbari, A and Berman, L and Gichoya, JW and Righetto, L and Samuel, D and Wasswa, W and Charalambides, M and Arora, A and Pujari, S and Summers, C and Sapey, E and Wilkinson, S and Thakker, V and Denniston, A and Liu, X}, title = {Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.}, journal = {The Lancet. Digital health}, volume = {7}, number = {1}, pages = {e64-e88}, pmid = {39701919}, issn = {2589-7500}, mesh = {Humans ; Algorithms ; Artificial Intelligence ; Bias ; *Consensus ; Datasets as Topic ; *Delphi Technique ; }, abstract = {Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective.}, } @article {pmid39700666, year = {2024}, author = {Palladini, M and Mazza, MG and De Lorenzo, R and Spadini, S and Aggio, V and Bessi, M and Calesella, F and Bravi, B and Rovere-Querini, P and Benedetti, F and , }, title = {Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors.}, journal = {Cytokine}, volume = {186}, number = {}, pages = {156839}, doi = {10.1016/j.cyto.2024.156839}, pmid = {39700666}, issn = {1096-0023}, abstract = {Growing evidence suggests the neurobiological mechanism upholding post-COVID-19 depression mainly relates to immune response and subsequent unresolved low-grade inflammation. Herein we exploit a broad panel of cytokines serum levels measured in COVID-19 survivors at one- and three-month since infection to predict post-COVID-19 depression. 87 COVID survivors were screened for depressive symptomatology at one- and three-month after discharge through the Beck Depression Inventory (BDI-13) and the Zung Self-Rating Depression Scale (ZSDS) at San Raffaele Hospital. Blood samples were collected at both timepoints and analyzed through Luminex. We entered one-month 42 inflammatory compounds into two separate penalized logistic regression models to evaluate their reliability in identifying COVID-19 survivors suffering from clinical depression at the two timepoints, applied within a machine learning routine. Delta values of analytes lowering between timepoints were entered in a third model predicting presence long-term depression. 5000 bootstraps were computed to determine significance of predictors. The cross-sectional model reached a balance accuracy (BA) of 76 % and a sensitivity of 70 %. Post-COVID-19 depression was predicted by high levels of CCL17, CCL22. On the other hand, CXCL10, CCL2, CCL3, CCL8, CXCL5, CCL15, CCL23, CXCL13, and GM-CSF showed protective effects. The longitudinal model obtained good performance as well (BA = 74 % and sensitivity = 68 %), revealing CXCL16 and CCL25 as additional drivers of clinical depression. Moreover, dynamic changes of analytes over time accurately predicted long-term depression (BA = 76 % and sensitivity = 75 %). Our findings unveil a putative immune profile upholding post-COVID-19 depression, thus reinforcing the need to deepen molecular mechanisms to appropriately target depression.}, } @article {pmid39700491, year = {2024}, author = {Dassaye, R and Chetty, T and Daniels, B and Gaffoor, Z and Spooner, E and Ramraj, T and Mthethwa, N and Nsibande, DF and Pillay, S and Bhana, A and Magasana, V and Reddy, T and Mohlabi, K and Moore, PL and Burgers, WA and de Oliveira, T and Msomi, N and Goga, A}, title = {SARS-CoV-2 Infections in a Triad of Primary School Learners (Grades 1-7), Their Parents, and Teachers in KwaZulu-Natal, South Africa: Protocol for a Cross-Sectional and Nested Case-Cohort Study.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e52713}, pmid = {39700491}, issn = {1929-0748}, mesh = {Humans ; *COVID-19/epidemiology/transmission ; South Africa/epidemiology ; Cross-Sectional Studies ; Child ; *Parents ; *School Teachers ; *Schools ; Cohort Studies ; Male ; Female ; Students/statistics & numerical data ; SARS-CoV-2/immunology ; Pilot Projects ; Seroepidemiologic Studies ; Adolescent ; Adult ; }, abstract = {BACKGROUND: In low- and middle-income countries (LMICs) such as South Africa, there is paucity of data on SARS-CoV-2 infections among children attending school, including seroprevalence and transmission dynamics.

OBJECTIVE: This pilot study aims to assess (1) the prevalence of self-reported or confirmed SARS-CoV-2 prior infections, COVID-19 symptoms (including long COVID), seroprevalence of SARS-CoV-2 antibodies, and general/mental health, (2) longitudinal changes in SARS-CoV-2 seroprevalence, and (3) SARS-CoV-2 acute infections, immune responses, transmission dynamics, and symptomatic versus asymptomatic contacts in a unique cohort of unvaccinated primary school learners, their parents, teachers, and close contacts in semirural primary school settings.

METHODS: Learners (grades 1-7) from primary schools in KwaZulu-Natal, South Africa, their parents, and teachers will be invited to enroll into the COVID kids school study (CoKiDSS). CoKiDSS comprises 3 parts: a cross-sectional survey (N=640), a follow-up survey (n=300), and a nested case-cohort substudy. Finger-prick blood and saliva samples will be collected for serological and future testing, respectively, in the cross-sectional (451 learners:147 parents:42 teachers) and follow-up (210 learners:70 parents:20 teachers) surveys. The nested case-cohort substudy will include cases from the cross-sectional survey with confirmed current SARS-CoV-2 infection (n=30) and their close contacts (n=up to 10 per infected participant). Finger-prick blood (from all substudy participants), venous blood (from cases), and nasal swabs (from cases and contacts) will be collected for serological testing, immunological testing, and viral genome sequencing, respectively. Questionnaires covering sociodemographic and general and mental health information, prior and current SARS-CoV-2 symptoms and testing information, vaccination status, preventative behavior, and lifestyle will be administered. Statistical methods will include generalized linear mixed models, intracluster correlation, descriptive analysis, and graphical techniques.

RESULTS: A total of 645 participants were enrolled into the cross-sectional survey between May and August 2023. A subset of 300 participants were followed up in the follow-up survey in October 2023. Screening of the participants into the nested case-cohort substudy is planned between November 2023 and September 2024. Data cleanup and analysis for the cross-sectional survey is complete, while those for the follow-up survey and nested case substudy will be completed by the third quarter of 2024. The dissemination and publication of results is anticipated for the fourth quarter of 2024.

CONCLUSIONS: This study provides data from an LMIC setting on the impact of SARS-CoV-2 on school-attending learners, their parents, and teachers 3 years after the SARS-CoV-2 pandemic was declared and 21-24 months after resumption of normal school attendance. In particular, this study will provide data on the prevalence of self-reported or confirmed SARS-CoV-2 prior infection, prior and current symptoms, seroprevalence, changes in seroprevalence, SARS-CoV-2 transmission, SARS-CoV-2 adaptive immune responses, and symptoms of long COVID and mental health among a triad of learners, their parents, and teachers.

DERR1-10.2196/52713.}, } @article {pmid39700067, year = {2024}, author = {Ford, ND and Agedew, A and Dalton, AF and Pratt, C and Gregory, CO and Saydah, S}, title = {Notes from the Field: Long COVID and Significant Long COVID-Associated Activity Limitation Among Adults, by Jurisdiction - United States, 2023.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {73}, number = {50}, pages = {1142-1143}, pmid = {39700067}, issn = {1545-861X}, } @article {pmid39699129, year = {2024}, author = {Deng, Y and Tong, Y and Zhang, Y and Liu, M}, title = {The Effects of COVID-19 on Anxiety and Depressive Symptoms Among Chinese College Students: Chain Mediation of Three Long COVID-19 Symptoms.}, journal = {The Journal of psychology}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/00223980.2024.2437382}, pmid = {39699129}, issn = {1940-1019}, abstract = {Long COVID has become a public health issue, and anxiety and depressive symptoms have been on the rise among young people since the COVID-19 pandemic. The primary purpose of this study was to survey the status of COVID-19 infection, long COVID, and mental health among Chinese college students after China lifted the dynamic zero-COVID policy on December 7, 2022. The secondary purpose was to explore the mediation effect of long COVID on the relationship between COVID-19 and anxiety and depressive symptoms. A total of 958 Chinese college students (Mage = 18.68, ages 16-22, 78.2% were female) completed measures of the severity of COVID-19, long COVID somatic symptom, insomnia, fatigue, anxiety, and depressive symptoms. Four potential chain mediation models was used to examine the role of long COVID somatic symptoms, insomnia, and fatigue as mediators between COVID-19 and anxiety and depressive symptoms. The results showed that ∼80% of Chinese college students suffered COVID-19 in late 2022 and early 2023, and 47.8, 35.4, 43.8, 37, and 54.3% of the participants had at least one somatic symptom, insomnia, fatigue, anxiety, and depressive symptoms, respectively, about 2-3 months after onset. This study revealed that the influence of COVID-19 on anxiety and depressive symptoms is not determined by the severity of COVID-19 in acute phase but by long COVID. Long COVID somatic symptoms, insomnia, and fatigue played mediation effects in different degree between COVID-19 and anxiety and depressive symptoms. Interventions that target long COVID may improve anxiety and depressive symptoms of Chinese college students who have had COVID-19.}, } @article {pmid39698216, year = {2024}, author = {Joshi, SH and Siddarth, P and Lavretsky, H}, title = {Structural MRI correlates of cognitive and neuropsychiatric symptoms in Long COVID: a pilot study.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1412020}, pmid = {39698216}, issn = {1664-0640}, abstract = {Approximately 7% of COVID-19 patients (1.3% children) have exhibited symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, and 20% of those present with neuropsychiatric symptoms. While a large number of MRI-based neuroimaging studies in this population have shown cortical atrophy in terms of gray matter volume and cortical thickness in patients, there is a growing body of work showing brain volume enlargements or thickness increases in patients compared to COVID negative controls. To investigate this further, we used structural magnetic resonance imaging (MRI) to examine differences in gray matter thickness for the cortical limbic and the dorsolateral prefrontal cortical regions between patients with Long COVID and healthy controls. Results showed increased cortical thickness in the caudal anterior, isthmus, and the posterior cingulate gyrus as well as the rostral middle frontal gyrus respectively along with higher gray matter volume in the posterior cingulate and the isthmus cingulate in patients with Long COVID. Cortical thickness and gray matter volumes for regions of interest (ROIs) were also associated with the severity measures, clinical dementia rating, and anxiety scores in the Long COVID group. Our findings provide supporting evidence for cortical hypertrophy in Long COVID.}, } @article {pmid39697632, year = {2024}, author = {Fanelli, M and Petrone, V and Chirico, R and Radu, CM and Minutolo, A and Matteucci, C}, title = {Flow cytometry for extracellular vesicle characterization in COVID-19 and post-acute sequelae of SARS-CoV-2 infection.}, journal = {Extracellular vesicles and circulating nucleic acids}, volume = {5}, number = {3}, pages = {417-437}, pmid = {39697632}, issn = {2767-6641}, abstract = {Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection.}, } @article {pmid39696010, year = {2024}, author = {Lin, F and Hao, S and Xiao, X and Li, X}, title = {Association between Hepatitis B virus infection and COVID-19: outcomes from clinical analysis and online survey from Beijing, China.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1438}, pmid = {39696010}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; *Hepatitis B, Chronic/complications/epidemiology/drug therapy ; Adult ; *SARS-CoV-2 ; Beijing/epidemiology ; Antiviral Agents/therapeutic use ; Incidence ; Surveys and Questionnaires ; Aged ; Hepatitis B virus/isolation & purification ; DNA, Viral ; China/epidemiology ; }, abstract = {OBJECTIVE: We aim to investigate whether Coronavirus disease 2019 (COVID-19) worsens chronic hepatitis B virus(HBV)infection and explore the incidence of long COVID symptoms in patients with chronic hepatitis B virus infection.

METHODS: Patients with chronic HBV infection and COVID-19 patients attending the hepatitis clinic or fever clinic were included in the study. Clinical manifestations of COVID-19 and information about long COVID were collected for all patients. For patients with chronic hepatitis B virus infection, laboratory test results such as HBV-DNA, liver function, and kidney function were collected three months before and after COVID-19.

RESULTS: A total of 940 patients with COVID-19 were included in this study. These patients were divided into two groups: the hepatitis B virus infection group with 189 patients and the non-hepatitis B group with 751 patients. Further matching analysis was conducted, selecting 156 patients from each group. Within the hepatitis B group, patients were further divided into two subgroups based on whether they received antiviral therapy: 90 patients in the antiviral therapy group and 99 patients in the non-antiviral therapy group. Neither group experienced a significant increase in HBV-DNA after COVID-19. There were significant differences between the two groups regarding BMI and symptoms of sore throat, loss of smell, and nasal congestion during COVID-19. The incidence of long COVID symptoms was higher in the hepatitis B group compared to the non-hepatitis B group (64.1% vs. 48.7%, p < 0.001), with the top five symptoms being cough, fatigue, palpitations, insomnia, and memory impairment.

CONCLUSION: Patients with chronic HBV infection did not show a significant rise in HBV DNA after COVID-19 in this study. They had a lower incidence of COVID-19 symptoms but experienced a higher incidence of long COVID symptoms.}, } @article {pmid39694730, year = {2024}, author = {Charlton, BT and Goulding, RP and Jaspers, RT and Appelman, B and van Vugt, M and Wüst, RCI}, title = {Skeletal muscle adaptations and post-exertional malaise in long COVID.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tem.2024.11.008}, pmid = {39694730}, issn = {1879-3061}, abstract = {When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.}, } @article {pmid39693583, year = {2025}, author = {Nath, A and Kolson, DL}, title = {Reemerging Infectious Diseases and Neuroimmunologic Complications.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {12}, number = {1}, pages = {e200356}, pmid = {39693583}, issn = {2332-7812}, support = {R01 NS122570/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Animals ; *Communicable Diseases, Emerging ; COVID-19/complications ; }, abstract = {During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.}, } @article {pmid39693079, year = {2024}, author = {Geng, LN and Erlandson, KM and Hornig, M and Letts, R and Selvaggi, C and Ashktorab, H and Atieh, O and Bartram, L and Brim, H and Brosnahan, SB and Brown, J and Castro, M and Charney, A and Chen, P and Deeks, SG and Erdmann, N and Flaherman, VJ and Ghamloush, MA and Goepfert, P and Goldman, JD and Han, JE and Hess, R and Hirshberg, E and Hoover, SE and Katz, SD and Kelly, JD and Klein, JD and Krishnan, JA and Lee-Iannotti, J and Levitan, EB and Marconi, VC and Metz, TD and Modes, ME and Nikolich, JŽ and Novak, RM and Ofotokun, I and Okumura, MJ and Parthasarathy, S and Patterson, TF and Peluso, MJ and Poppas, A and Quintero Cardona, O and Scott, J and Shellito, J and Sherif, ZA and Singer, NG and Taylor, BS and Thaweethai, T and Verduzco-Gutierrez, M and Wisnivesky, J and McComsey, GA and Horwitz, LI and Foulkes, AS and , }, title = {2024 Update of the RECOVER-Adult Long COVID Research Index.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2024.24184}, pmid = {39693079}, issn = {1538-3598}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {IMPORTANCE: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.

OBJECTIVE: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.

Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: Presence of LC and participant-reported symptoms.

RESULTS: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures.

CONCLUSIONS AND RELEVANCE: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.}, } @article {pmid39692474, year = {2024}, author = {Herbert, C and Antar, AAR and Broach, J and Wright, C and Stamegna, P and Luzuriaga, K and Hafer, N and McManus, DD and Manabe, YC and Soni, A}, title = {Relationship Between Acute Severe Acute Respiratory Syndrome Coronavirus 2 Viral Clearance and Long Coronavirus 2019 (Long COVID) Symptoms: A Cohort Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciae539}, pmid = {39692474}, issn = {1537-6591}, support = {/NH/NIH HHS/United States ; 3U54HL143541-02S2//Rapid Acceleration of Diagnostics (RADx) Tech program/ ; }, abstract = {BACKGROUND: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics during acute infection and the development of long coronavirus disease 2019 (COVID-19), or "long COVID," is largely unknown.

METHODS: Between October 2021 and February 2022, 7361 people not known to have COVID-19 self-collected nasal swab samples for SARS-CoV-2 reverse-transcription polymerase chain reaction testing every 24-48 hours for 10-14 days. Participants whose first known SARS-CoV-2 infection was detected were surveyed for long COVID in August 2023. Their slopes of viral clearance were modeled using linear mixed effects models with random slopes and intercepts, and the relative risk (RR) of long COVID based on viral slopes was calculated using a log binomial model, adjusted for age, symptoms, and variant. Sex-based interaction terms were also evaluated for significance.

RESULTS: A total of 172 participants were eligible for analyses, and 59 (34.3%) reported long COVID. The risk of long COVID with 3-4 symptoms (adjusted RR, 2.44 [95% confidence interval, .88-6.82]) and ≥5 symptoms (4.97 [1.90-13.0]) increased with each unit increase in slope of viral clearance. While the probability of long COVID increased with slowed viral clearance among women, the same relationship was not observed among men (interaction term: P = .02). Acute SARS-CoV-2 symptoms of abdominal pain (adjusted RR, 5.41 [95% confidence interval, 2.44-12.0]), nausea (3.01 [1.31-6.89]), and body aches (2.58 [1.26-5.30]) were most strongly associated with long COVID.

CONCLUSIONS: We observed that slower viral clearance rates during acute COVID-19 were associated with increased risk and more symptoms of long COVID . Early viral-host dynamics appear to be mechanistically linked to the development of long COVID.}, } @article {pmid39691709, year = {2024}, author = {Missailidis, D and Ebrahimie, E and Dehcheshmeh, MM and Allan, C and Sanislav, O and Fisher, P and Gras, S and Annesley, SJ}, title = {A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1450853}, pmid = {39691709}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/genetics/immunology/virology/diagnosis ; Male ; *SARS-CoV-2/physiology/genetics/immunology ; Female ; *Leukocytes, Mononuclear/metabolism/virology/immunology ; Middle Aged ; *RNA, Messenger/genetics ; Transcriptome ; Pilot Projects ; Biomarkers ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Gene Expression Profiling ; }, abstract = {INTRODUCTION: Long COVID is a debilitating condition that lasts for more than three months post-infection by SARS-CoV-2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.

METHODS: In this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.

RESULTS: Seventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as ICOS (FDR p = 0.024) and S1PR1 (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors LILRB1 (FDR p = 0.005) and LILRB2 (FDR p = 0.027). PCA analysis demonstrated that LILRB1 and LILRB2 expression discriminated all of the Long COVID samples from COVID recovered samples.

DISCUSSION: Downregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. LILRB1 and LILRB2 should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions.}, } @article {pmid39688913, year = {2024}, author = {Tsao, T and Buck, AM and Grimbert, L and LaFranchi, BH and Altamirano Poblano, B and Fehrman, EA and Dalhuisen, T and Hsue, PY and Kelly, JD and Martin, JN and Deeks, SG and Hunt, PW and Peluso, MJ and Aguilar, OA and Henrich, TJ}, title = {Long COVID is associated with lower percentages of mature, cytotoxic NK cell phenotypes.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI188182}, pmid = {39688913}, issn = {1558-8238}, } @article {pmid39686622, year = {2024}, author = {Hadidchi, R and Pakan, R and Alamuri, T and Cercizi, N and Al-Ani, Y and Wang, SH and Henry, S and Duong, TQ}, title = {Long COVID-19 outcomes of patients with pre-existing dementia.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877241303934}, doi = {10.1177/13872877241303934}, pmid = {39686622}, issn = {1875-8908}, abstract = {BACKGROUND: Although COVID-19 has been linked to worse acute outcomes in patients with some neurodegenerative disorders, its long-term impact on dementia remains unclear.

OBJECTIVE: To investigate the outcomes of COVID-19 survivors with dementia.

METHODS: This retrospective study evaluated 9806 patients with dementia in the Montefiore Health System (January 2016 to July 2023). Comparisons were made between dementia patients with and without a positive SARS-CoV-2 polymerase-chain-reaction test who had a follow-up at least two weeks post-infection. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), new-onset dysphagia, dyspnea, fatigue, new-onset sleep disturbances, altered mental status, first-time fall, headache, new-onset depression, and new-onset anxiety. Adjusted hazard ratios (aHR) were computed adjusting for age, sex, race, ethnicity, and pre-existing comorbidities.

RESULTS: Dementia patients with COVID-19 were younger, more likely to be male, and had a higher prevalence of major pre-existing comorbidities compared to those without COVID-19. Patients who survived acute COVID-19 were more likely to die than non-COVID controls after adjusting for covariates (aHR = 1.65 [1.43, 1.91]). COVID-19 was significantly associated with higher risk of MACE (aHR = 1.58 [1.41, 1.78]), new-onset dysphagia (aHR = 1.64 [1.42, 1.91]), dyspnea (aHR = 1.27 [1.12, 1.44]), fatigue (aHR = 1.42 [1.22, 1.65]), new-onset sleep disturbances (aHR = 1.36 [1.15, 1.60]), altered mental status (aHR = 1.36 [1.16, 1.59]), and first-time fall (aHR = 1.34 [1.09, 1.65]).

CONCLUSIONS: COVID-19 increases the risk of mortality and other adverse health outcomes in dementia patients. These findings highlight the need for closer follow-up and management strategies for dementia patients post-COVID-19.}, } @article {pmid39685729, year = {2024}, author = {Azar, G and Abdelmassih, Y and Bonnin, S and Guindolet, D and Vasseur, V and Behar Cohen, F and Salmon, D and Mauget-Faÿsse, M}, title = {Endothelial Glycocalyx Anomalies and Ocular Manifestations in Patients with Post-Acute COVID-19.}, journal = {Journal of clinical medicine}, volume = {13}, number = {23}, pages = {}, pmid = {39685729}, issn = {2077-0383}, abstract = {Objectives: To report ophthalmological and microvascular findings in patients with post-acute COVID-19. Methods: In this prospective, monocentric cohort study, we included patients with post-acute COVID-19 who presented with ophthalmological symptoms. All patients underwent indocyanine green angiography (ICGA), OCT, OCT-angiography, adaptive optics, and GlycoCheck assessments. Results: We included 44 patients, predominantly female (81.8%), with a mean age of 47.5 ± 11.5 years. Key ICGA findings revealed hyperreflective dots in 32 eyes (36.4%) and hemangioma-like lesions in 7 eyes (8.0%). Capillary non-perfusion in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was observed in 42 eyes (47.7%) and 21 eyes (23.9%), respectively. Eyes with hyperreflective dots exhibited a lower perfused boundary region (PBR), while those with superficial punctate keratitis showed a higher PBR (p = 0.02 and p = 0.002, respectively). Eyes with capillary non-perfusion in the SCP displayed lower capillary densities (CD4, CD5, and CD4-6; p = 0.001, 0.03, and 0.03, respectively), and eyes with non-perfusion in the DCP had lower CD4 (p = 0.03). A negative correlation was identified between capillary density and the wall-to-lumen ratio. Conclusions: Patients with post-acute COVID-19 demonstrate both retinal and choroidal vascular anomalies. Ocular pathology was associated with reduced capillary density. These injuries appear to stem more from microvascular disruptions than from persistent glycocalyx abnormalities.}, } @article {pmid39685583, year = {2024}, author = {Serapide, F and Talarico, M and Rotundo, S and Pascale, V and Serraino, R and Trecarichi, EM and Russo, A}, title = {Lights and Shadows of Long COVID: Are Latent Infections the Real Hidden Enemy?.}, journal = {Journal of clinical medicine}, volume = {13}, number = {23}, pages = {}, pmid = {39685583}, issn = {2077-0383}, abstract = {Long COVID-19 (LC) is a poorly understood, multifactorial condition that persists for at least three months following SARS-CoV-2 infection. The underlying pathophysiological mechanisms responsible for the wide range of associated symptoms-including fatigue, brain fog, and respiratory issues-remain unclear. However, emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may significantly contribute to the complexity of LC. These latent viruses can be reactivated by SARS-CoV-2, contributing to a chronic inflammatory state that prolongs symptomatology. This review confirms the potential involvement of latent viral infections in LC and examines whether these infections play an independent role or act synergistically with other factors. In addition, recent studies have highlighted viral persistence and immune dysregulation as key elements in LC. Our findings suggest that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, show potential in reducing LC risk by preventing viral reactivation. However, tailored diagnostic and therapeutic strategies targeting these latent infections are urgently needed. Identifying biomarkers of viral reactivation, particularly for high-risk populations, could be considered another effective strategy to mitigate LC severity. Further research is crucial to better understand the interactions between SARS-CoV-2 and latent infections, and to improve the prevention and treatment of LC.}, } @article {pmid39684966, year = {2024}, author = {Onik, G and Knapik, K and Dąbrowska-Galas, M and Sieroń, K}, title = {Health Resort Treatment Improves Functioning and Physical Performance in Long COVID Patients: A Retrospective Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {23}, pages = {}, pmid = {39684966}, issn = {2227-9032}, abstract = {BACKGROUND/OBJECTIVES: The physical performance and functional status of individuals with long COVID may be altered. Health resort treatment comprises balneology, exercises, physical medicine modalities, and climate therapy. Complex treatment in a sanatorium may have a positive effect on long COVID patients. This study assessed functional status, physical performance, and fatigue in people with long COVID that qualified for the health resort treatment and its efficacy in this group of patients.

METHODS: A retrospective review of the medical records of 116 patients (66 women and 50 men) undergoing health resort treatment for long COVID in 2021 at the Rehabilitation Hospital and Sanatorium "Gwarek" in Goczałkowice-Zdrój (Poland) was conducted. Data were collected between March and May 2024. Their functional status, physical performance, and level of fatigue were assessed twice: before and after the treatment.

RESULTS: After the health resort treatment, their physical performance (10.41 points ± 1.84 points vs. 11.57 points ± 0.94 points; p < 0.00001) and functional status (2.13 points ± 0.88 points vs. 1.23 points ± 0.62 points; p < 0.00001) improved. Their fatigue (4.83 points ± 2.38 points vs. 2.15 points ± 1.31 points; p < 0.00001) level was diminished after the treatment.

CONCLUSIONS: Fatigue was of moderate intensity in the long COVID patients that qualified for the health resort treatment. Most of the long COVID patients reported mild functional limitations, whereas their physical performance was undisturbed. Health resort treatment improved functioning in patients with persistent COVID-19 symptoms by reducing fatigue, improving their functional capacity and physical performance. It should be recommended as a supplement to the standard treatment because of its complexity.}, } @article {pmid39684943, year = {2024}, author = {Sun, X and Di Fusco, M and Lupton, LL and Yehoshua, A and Alvarez, MB and Allen, KE and Puzniak, L and Lopez, SMC and Cappelleri, JC}, title = {Predictors of Long COVID Among Symptomatic US Adults Testing Positive for SARS-CoV-2 at a National Retail Pharmacy.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {23}, pages = {}, pmid = {39684943}, issn = {2227-9032}, support = {not available//Pfizer Inc./ ; }, abstract = {BACKGROUND: Long COVID remains a significant public health concern. This study investigated risk factors for long COVID in outpatient settings.

METHODS: A US-based prospective survey study (clinicaltrials.gov NCT05160636) was conducted in 2022 and replicated in 2023. Symptomatic adults testing positive for SARS-CoV-2 at CVS Pharmacies were recruited. CDC-based long COVID symptoms were collected at Week 4, Month 3, and Month 6 following SARS-CoV-2 testing. Logistic regression was used to develop a predictive model for long COVID using data from the 2022 cohort. The model was validated with data from the 2023 cohort. Model performance was evaluated with c-statistics.

RESULTS: Patients characteristics were generally similar between the 2022 (N = 328) and 2023 (N = 505) cohorts. The prevalence of long COVID defined as ≥3 symptoms at Month 6 was 35.0% and 18.2%, respectively. The risk factors associated with long COVID were older age, female sex, lack of up-to-date vaccination, number of acute symptoms on the day of SARS-CoV-2 testing, increase in symptoms at Week 1, underlying comorbidities and asthma/chronic lung disease. The c-statistic was 0.79, denoting good predictive power.

CONCLUSIONS: A predictive model for long COVID was developed for an outpatient setting. This research could help differentiate at-risk groups and target interventions.}, } @article {pmid39683627, year = {2024}, author = {Kawabata, K and Nakamura, K and Kanda, N and Hemmi, M and Suganuma, S and Muto, Y and Iba, A and Hori, M and Hosozawa, M and Iso, H and , }, title = {Risk Factors for Long-Term Nutritional Disorders One Year After COVID-19: A Post Hoc Analysis of COVID-19 Recovery Study II.}, journal = {Nutrients}, volume = {16}, number = {23}, pages = {}, pmid = {39683627}, issn = {2072-6643}, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Middle Aged ; Risk Factors ; Aged ; *SARS-CoV-2 ; *Malnutrition/etiology/epidemiology ; Nutrition Disorders/etiology ; Adult ; Nutritional Status ; Body Mass Index ; Hospitalization ; Time Factors ; }, abstract = {Background/Objectives: COVID-19 patients develop various clinical symptoms, including malnutrition. However, the risk factors for long-term nutritional disorders remain unclear. Identifying these factors is crucial for preventing nutritional disorders by initiating early nutritional interventions. Methods: This was a post hoc analysis of COVID-19 Recovery Study II (CORESII). The study included adult patients hospitalized for COVID-19 and discharged from the hospital. Information, including post-COVID-19 symptoms one month after onset and changes in daily life during the first year, was collected using a self-administered questionnaire sent one year after hospital discharge. We examined the association between baseline characteristics, disease severity, and symptoms that persisted one month after onset with malnutrition disorders one year after onset, defined as a Malnutrition Universal Screening Tool score ≥1, using a logistic regression analysis. Results: A total of 1081 patients (mean age of 56.0 years; 34% females; 38% admitted to the intensive care unit) were analyzed. Of these patients, 266 patients (24.6%) had malnutrition one year after onset. In a multivariable logistic regression analysis using variables that were significant in a univariate logistic regression analysis, the following factors were independently associated with malnutrition: BMI < 18.5 kg/m[2] (odds ratio [95% confidence interval (CI)], 48.9 [14.3-168]), 18.5 ≤ BMI ≤ 20 (10.5 [5.89-18.8]), 30 < BMI (2.64 [1.84-3.75]), length of hospital stay (1.01 [1.00-1.02]), maintenance dialysis (3.19 [1.19-8.61]), and difficulty concentrating one month after onset (1.73 [1.07-2.79]). Conclusions: Being underweight or obese, prolonged hospitalization, maintenance dialysis, and difficulty concentrating one month after onset were associated with a risk of malnutrition one year post-illness. Patients with these factors may be at a high risk of long-term nutritional disorders.}, } @article {pmid39682075, year = {2024}, author = {Kakad, UU and Khopkar-Kale, PS and Tripathy, SP and Bhawalkar, JS}, title = {Potential of melatonin as a treatment option for long COVID: A call for research.}, journal = {British journal of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bcp.16375}, pmid = {39682075}, issn = {1365-2125}, } @article {pmid39681609, year = {2024}, author = {Barz, A and Berger, J and Speicher, M and Morsch, A and Wanjek, M and Rissland, J and Jäger, J}, title = {Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition - a randomized controlled trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {30511}, pmid = {39681609}, issn = {2045-2322}, mesh = {Humans ; *Quality of Life ; Female ; Male ; *Fatigue/therapy ; Middle Aged ; *Exercise Therapy/methods ; *COVID-19/psychology ; Adult ; Aged ; SARS-CoV-2/isolation & purification ; Hand Strength ; Post-Acute COVID-19 Syndrome ; Exercise ; }, abstract = {Fatigue is the most prevalent symptom within the post-COVID condition (PCC). Furthermore, many patients suffer from decreased physical performance capacity and post-exertional malaise. Although exercise has been proposed as an effective therapeutic strategy for PCC, there is limited evidence on individualised and symptom-titrated exercise interventions in patients with fatigue and PEM. Therefore, we conducted a multi-centre randomised controlled trial to investigate the effectiveness of an individualised and symptom-titrated exercise program. We measured fatigue, health-related quality of life, hand-grip strength, endurance capacity and PEM before and after the 10-week intervention. A total of 118 individuals with PCC were included in the final intention-to-treat analysis. All tests and training sessions took place in commercial fitness and health facilities. We found significant effects on fatigue severity, health-related quality of life and physical performance capacity. Adjusting the individual exercise load to daily fatigue has proven to be an effective and safe strategy in PCC patients with fatigue. Under the guidance of qualified professionals and by utilising symptom-titrated training recommendations, commercial fitness and health facilities present an appropriate setting for outpatient exercise rehabilitation in PCC.}, } @article {pmid39681396, year = {2024}, author = {Rossman, JS and van der Togt, V}, title = {Recovery is missing in the pandemic treaty.}, journal = {BMJ (Clinical research ed.)}, volume = {387}, number = {}, pages = {q2827}, doi = {10.1136/bmj.q2827}, pmid = {39681396}, issn = {1756-1833}, } @article {pmid39680873, year = {2024}, author = {Díaz de León-Martínez, L and Flores-Rangel, G and Alcántara-Quintana, LE and Mizaikoff, B}, title = {A Review on Long COVID Screening: Challenges and Perspectives Focusing on Exhaled Breath Gas Sensing.}, journal = {ACS sensors}, volume = {}, number = {}, pages = {}, doi = {10.1021/acssensors.4c02280}, pmid = {39680873}, issn = {2379-3694}, abstract = {Long COVID (LC) is a great global health concern, affecting individuals recovering from SARS-CoV-2 infection. The persistent and varied symptoms across multiple organs complicate diagnosis and management, and an incomplete understanding of the condition hinders advancements in therapeutics. Current diagnostic methods face challenges related to standardization and completeness. To overcome this, new technologies such as sensor-based electronic noses are being explored for LC assessment, offering a noninvasive screening approach via volatile organic compounds (VOC) sensing in exhaled breath. Although specific LC-associated VOCs have not been fully characterized, insights from COVID-19 research suggest their potential as biomarkers. Additionally, AI-driven chemometrics are promising in identifying and predicting outcomes; despite challenges, AI-driven technologies hold the potential to enhance LC evaluation, providing rapid and accurate diagnostics for improved patient care and outcomes. This review underscores the importance of emerging and sensing technologies and comprehensive diagnostic strategies to address screening and treatment challenges in the face of LC.}, } @article {pmid39679736, year = {2024}, author = {Chan, YJ and Chen, CC and Tu, YK and Hsu, WH and Tsai, YW and Liu, TH and Huang, PY and Chuang, MH and Hung, KC and Lee, MC and Yu, T and Lai, CC and Weng, TC and Wu, JY}, title = {The Effectiveness of COVID-19 Vaccination on Post-Acute Sequelae of SARS-CoV-2 Infection Among Geriatric Patients.}, journal = {Journal of medical virology}, volume = {96}, number = {12}, pages = {e70119}, doi = {10.1002/jmv.70119}, pmid = {39679736}, issn = {1096-9071}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/prevention & control/mortality/epidemiology ; Aged ; Male ; Female ; Retrospective Studies ; *COVID-19 Vaccines/administration & dosage/immunology ; Aged, 80 and over ; *SARS-CoV-2/immunology ; *Vaccination/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {This study aims to evaluate the effectiveness of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing the post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as long COVID, and reducing all-cause mortality among older patients. A retrospective cohort study was conducted using the TriNetX database. The study cohort consisted of older patients (age ≥ 65 years) with their first COVID-19 illness between January 1, 2022, and May 31, 2024. Participants were divided into vaccinated and unvaccinated groups based on their vaccination status. Propensity score matching (PSM) was used to balance baseline characteristics. Cox regression models and log-rank tests were applied to estimate the hazard ratio (HR) for PASC and all-cause mortality during 30-180 days of follow-up. The study included 189 059 geriatric patients who contracted SARS-CoV-2, with 5615 vaccinated and 183 444 unvaccinated. After PSM, each group contained 5615 patients. Vaccinated patients exhibited a significantly lower incidence of PASC symptoms (HR = 0.852, 95% CI: 0.778-0.933, p = 0.0005), particularly anxiety and depression, with a HR of 0.710 (95% CI: 0.575-0.878, p = 0.0015). Vaccination was also significantly associated with reduced all-cause mortality (HR = 0.231, 95% CI: 0.136-0.394, p < 0.0001). The findings highlight the effectiveness of COVID-19 vaccination in mitigating the development of PASC and decreasing mortality among older patients.}, } @article {pmid39679484, year = {2024}, author = {Grassi, T and Tiple, D and Villa, M and Grisetti, T and Pricci, F and Floridia, M and Giuliano, M and Castriotta, L and Rosolen, V and Beorchia, Y and Fanizza, C and Bisceglia, L and Francesconi, P and Profili, F and Bonaccorsi, G and Bruschi, M and Onder, G}, title = {[Analysis of the long-term effects of COVID-19 infection (long-COVID) in Italy during and after the pandemic emergency and response strategy].}, journal = {Epidemiologia e prevenzione}, volume = {48}, number = {6}, pages = {438-448}, doi = {10.19191/EP24.6.A786.135}, pmid = {39679484}, issn = {1120-9763}, mesh = {*COVID-19/epidemiology ; Humans ; Italy/epidemiology ; *Pandemics ; *SARS-CoV-2 ; *Hospitalization/statistics & numerical data ; Female ; Male ; Aged ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Adult ; Time Factors ; Health Resources/supply & distribution ; Aged, 80 and over ; }, abstract = {BACKGROUND: the long-COVID condition is gaining increasing relevance in terms of public health, but few studies have evaluated its impact on use of healthcare resources and the organizational responses of healthcare systems. Although many studies have evaluated case studies of individuals with long-COVID, the clinical spectrum of symptoms is still poorly defined due to the heterogeneity of the populations studied, the variability of the definitions used, and the absence of disease markers. In this context, in 2022, a project was designed and implemented in cooperation between the National Centre for Prevention and Control of the Italian Ministry of Health and the Italian National Health Institute (Istituto Superiore di Sanità, ISS).

OBJECTIVES AND METHODS: this project was articulated into five main objectives: 1. definition of the health care dimensions of the long-COVID phenomenon. This objective included an analysis of regional data flows to measure use of hospitalization services (acute, rehabilitation, long-term care), resource consumption (specialist visits and drug consumption), and the rate of institutionalization in patients with a history of COVID-19; 2. definition of number, characteristics, and distribution of long-COVID centres across the national territory. This objective has been implemented through a national survey of long-COVID diagnosis and assistance centres; 3. definition of clinical good practices about the management of long-COVID condition by a multidisciplinary group of experts; 4. definition of a long-COVID surveillance system; including the definition of a specific data set of information and the identification of a sample of clinical centres that deal with the care of subjects with long-term effects of COVID-19 and the setup of a dedicated online platform; a phone survey based on more than 1,000 interviews assessed the spectrum of symptoms reported; 5. structuring a national network and providing information, which included networking of the centres participating in the study with the dissemination of periodic information and update workshops or webinars; the creation of a website dedicated to the long-COVID condition, with general information for citizens and a section dedicated to the project; training activities.

RESULTS: Objective 1: a cohort study of over 600,000 individuals showed that people exposed to SARS-CoV-2 infection, particularly those who were hospitalized, appear to use more healthcare resources in the 6 months following infection than those who were not exposed. Individuals hospitalized in intensive care showed rates of outpatient visits 3 times higher than those who were not exposed and over 4 times higher rates for diagnostic imaging tests and hospitalizations. The case-control study found an increased risk of initiating antidepressant therapy among individuals exposed to SARS-CoV-2 infection compared to those who were not exposed, particularly among those who were hospitalized during acute infection. Furthermore, COVID-19 vaccination may play a protective role in this context. Objective 2: 124 clinical centres completed the questionnaire developed to define the patterns of clinical care for patients with long-COVID. Most centres provided care through outpatient visits or day hospital services with scheduled visits or referral to primary care and had specialist skills that allowed a multidisciplinary approach to the subject with suspected long-COVID condition. Objective 3: a multidisciplinary team, representative of the multi-systemic nature of long-COVID, with the participation of 16 experts, developed recommendations for the management of patients with long-COVID, based on current knowledge on the topic, with the aim of contributing to standardizing the activities of clinical centres throughout Italy. Objective 4: the clinical surveillance system has allowed the collection of data from over 1,200 patients from 30 clinical centres for the definition of symptom, their aggregation in clusters, and associated factors. Information on symptom profile was also assessed through a phone survey of more than 1,000 participants. Objective 5: the ISS website on long COVID provided information on the long-COVID condition and illustrated the CCM project, with links to webinars and workshops. In addition, a FAD course - entitled 'long-COVID: a new clinical scenario' - was implemented on the EDU-ISS platform, with over 14,000 participants.

CONCLUSIONS: the results of this study show that long-COVID is a frequent condition in our country, which, due to the amplitude of numbers and the spectrum of symptoms, has a substantial impact on resource consumption. This demonstrates that it will be necessary to implement, guarantee and monitor well-defined care standards for this condition.}, } @article {pmid39679212, year = {2024}, author = {Zhu, X and Li, Y and Wang, J and Gao, W}, title = {Clinical Features of Long COVID Patients Coinfected With Mycoplasma pneumoniae.}, journal = {The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2024}, number = {}, pages = {7213129}, pmid = {39679212}, issn = {1712-9532}, abstract = {Background: Since the SARS-CoV-2 pandemic, many patients have suffered prolonged complications, called "long COVID." Mycoplasma pneumoniae is a common respiratory pathogen. Reports of simultaneous long COVID and M. pneumoniae infections are rare in the literature. Methods: We analyzed the clinical data of patients with long COVID-19 who visited the Respiratory Clinic of The Affiliated Hospital of Hangzhou Normal University between January 1 and January 31, 2023, together with their laboratory and radiographic findings, with Pearson's χ [2] test. Results: Fifty-two patients diagnosed with both long COVID and M. pneumoniae infection and 77 with long COVID only were compared. The ages, clinical symptoms, and comorbidities of the two groups did not differ significantly (p > 0.05). However, sex and imaging findings differed between the groups. Conclusions: Our study showed that long COVID-M. pneumoniae coinfection was more commonly seen in females and patients with typical chest computed tomography (CT) images.}, } @article {pmid39678231, year = {2024}, author = {Khan, MWZ and Ahmad, M and Qudrat, S and Afridi, F and Khan, NA and Afridi, Z and Fahad, and Azeem, T and Ikram, J}, title = {Vagal nerve stimulation for the management of long COVID symptoms.}, journal = {Infectious medicine}, volume = {3}, number = {4}, pages = {100149}, pmid = {39678231}, issn = {2772-431X}, abstract = {This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms following acute SARS-CoV-2 infection. Long COVID manifests as ongoing fatigue, cognitive impairment, and autonomic dysfunction, hypothesized to arise from sustained inflammatory and neurological dysregulation. The vagus nerve, central to modulating systemic inflammation and autonomic homeostasis, represents a promising therapeutic target for symptom alleviation through VNS. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies evaluating VNS in the context of long COVID. Preliminary evidence from small-scale pilot studies suggests VNS may attenuate systemic inflammation through activation of the cholinergic anti-inflammatory pathway (CAP), thus restoring autonomic balance and ameliorating symptoms such as fatigue, cognitive dysfunction, and anxiety. In targeting the inflammatory cascade that underlies both acute COVID-19 pathophysiology and its prolonged sequelae, VNS holds potential as an innovative intervention for persistent post-viral symptoms. While these initial findings indicate promise, current data remain limited in scope and robustness, underscoring the need for larger, controlled trials to validate the efficacy and mechanisms of VNS in long COVID management. Establishing a clearer understanding of VNS's impact on inflammation and autonomic regulation in this context is crucial to inform clinical guidelines and therapeutic strategies for long COVID, potentially offering a targeted approach for mitigating this disabling condition.}, } @article {pmid39677538, year = {2024}, author = {Brunckhorst, B and Cojocaru, A and Kim, YS and Kugler, M}, title = {Long COVID: The evolution of household welfare in developing countries during the pandemic.}, journal = {World development}, volume = {175}, number = {}, pages = {106485}, pmid = {39677538}, issn = {0305-750X}, abstract = {This study examines household welfare dynamics during the COVID-19 pandemic, using harmonized data from over 300 phone surveys in 80 countries during 2020 and 2021, representing more than 2.5 billion people. The analysis traces out the evolution of employment and income across and within countries as restrictions on economic activity were relaxed. We show some groups initially experiencing higher rates of employment loss - including women, informal workers, and those with less education - also recovered jobs at a slower pace. Based on panel regressions, changes in policy stringency were associated with unequal employment outcomes. Labor market transitions were toward jobs of inferior quality on average, especially for workers with less education. Household income dynamics suggest uneven impacts in the intensive margin of employment consistent with these transitions. Lower wages were not offset by additional social assistance. Taken together, these dynamics may amplify the inequality impacts of the pandemic over the medium to long term.}, } @article {pmid39677088, year = {2024}, author = {Barata, A and Sebastião, M and Sampaio, N and Lima, L and Cruz, I and Antunes, I}, title = {Long COVID Following Mild SARS-CoV-2 Infection: A Retrospective Study in a Portuguese Primary Health Care Unit.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73655}, pmid = {39677088}, issn = {2168-8184}, abstract = {INTRODUCTION: Long COVID is a recent pathological entity. Its manifestations and impact on health and quality of life and, on a larger scale, at an economic and social level may be very significant, reflecting a challenge for the future. The family doctor plays a major role in the care of these patients and must be aware of this new reality. With this study, we aim to determine the prevalence of long COVID in the adult population registered in a Portuguese Primary Healthcare Unit, called USF Amatus, and identify the most frequent symptoms, its duration, and impact on the quality of life of individuals.

METHODS: This is a retrospective study based on the analysis of the national database of COVID-19 (Trace COVID-19), selecting patients ≥ 18 years old registered in USF Amatus, diagnosed with mild COVID-19, in the period between March 2020 and March 2022. The selected patients were submitted to a telephone interview to fill a questionnaire adapted from the World Health Organization "Report Form for Post COVID Condition" to the Portuguese population by the Directorate-General of Health (DGS). The collected data were analyzed using statistical software (R Development Core Team; Vienna, Austria) and the package "ggplot2".

RESULTS: A total sample of 334 (56% female) was recruited for this study. The prevalence of long COVID was found to be 145 (43.4%) cases in the near months (≥ 3 months) following COVID-19 and 57 (17.1%) cases after two years. The most frequently reported symptoms were fatigue, persistent muscle pain, post-exercise malaise, memory loss, leg/arm weakness, and dizziness/lightheadedness. About 58 (17.4%) patients reported that their self-care capacity became worse after COVID-19. In the further evaluation of functional status, 56 (16.8%) patients reported that walking a distance of at least 1 km is more difficult nowadays, and 29 (8.7%) reported that performing household tasks became harder.

CONCLUSION: This study demonstrates the relevance of long COVID. The findings reveal a significant prevalence of symptomatic patients even two years after the infection with SARS-CoV-2. The most commonly reported symptom was fatigue. Other prevalent symptoms were neurocognitive, muscular, and physical exercise intolerance. It is also important to mention the relevant impact of long COVID on the quality of life of these patients. Further research is needed in order to better understand long COVID and, consequently, develop more directed and effective interventions for these patients, contributing to their well-being at an individual, familial, and social level.}, } @article {pmid39674281, year = {2024}, author = {Albastaki, E}, title = {Letter to the Editor on Improving quality in adult long covid services. Implementing discrete event simulation, a quality improvement proposition.}, journal = {Clinical medicine (London, England)}, volume = {}, number = {}, pages = {100280}, doi = {10.1016/j.clinme.2024.100280}, pmid = {39674281}, issn = {1473-4893}, } @article {pmid39673304, year = {2024}, author = {Akgun, Y}, title = {The potential of plasma exchange in treating Chronic Fatigue Syndrome and long COVID: Targeting autoimmune and inflammatory mechanisms.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.18099}, pmid = {39673304}, issn = {1537-2995}, } @article {pmid39673203, year = {2024}, author = {Grant, A and Adams, NN and MacIver, E and Skåtun, D and Scott, N and Kennedy, C and Douglas, F and Hernandez-Santiago, V and Torrance, N}, title = {Long COVID in healthcare workers: longitudinal mixed-methods study.}, journal = {Occupational medicine (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/occmed/kqae113}, pmid = {39673203}, issn = {1471-8405}, abstract = {BACKGROUND: Healthcare workers (HCWs) report higher rates of long coronavirus disease (COVID) (LC) than other occupational groups. It is still unclear whether LC is a lifelong condition. Workforce shortfalls are apparent due to sick leave, reduced hours and lower productivity.

AIMS: To investigate the lived experience of LC on a range of HCWs, including impact on health-related quality-of-life (HRQL), use of health services, working and personal lives and household finances.

METHODS: Longitudinal mixed methods with online surveys and qualitative interviews 6-months apart. HCWs including healthcare professionals, ancillary and administration staff who self-report LC were recruited through social media and National Health Service channels. Interviewees were purposively sampled from survey responses.

RESULTS: The first survey was completed by 471 HCWs (S1) and 302 (64%) the follow-up (S2). A total of 50 HCWs were interviewed initially and 44 at second interview. All participants experienced various relapsing, remitting, changing and prolonged LC symptoms (mean 7.1 [SD 4.8] at S2) and a third reported day-to-day activities 'limited a lot'. Most participants were working in a reduced capacity: reduced hours, different role or location. Healthcare was limited, and often unsatisfactory. Participants feared reinfection, their future, ability to work and financial security (59% (n = 174) at S2). They experienced stigma, distress, grief for their former self and some felt unsupported, however, as awareness of LC grew some experienced improved understanding and support.

CONCLUSIONS: Most participants continued working, managing complex and dynamic symptoms effecting their everyday life and ability to work. Most did not report significant improvements over time and feared for their future and financial security.}, } @article {pmid39673190, year = {2025}, author = {Sepic, A and Tryfonos, A and Rundqvist, H and Lundberg, TR and Gustafsson, T and Pourhamidi, K}, title = {Non-Hospitalized Patients With Post-COVID Condition and Myopathic Electromyography Findings Show no Difference in Symptom Severity and Clinical Manifestations Compared to Those Without Myopathic Findings.}, journal = {Muscle & nerve}, volume = {71}, number = {2}, pages = {223-228}, pmid = {39673190}, issn = {1097-4598}, support = {//Magnus Bergvalls Stiftelse/ ; //Tore Nilsons Foundation/ ; //Hannover Foundation/ ; //Torespiran Foundation/ ; //Lars Hiertas Minne Foundation/ ; //Dr Margaretha Nilssons Foundation/ ; //Åke Wibergs Foundation/ ; //Center for Innovative Medicine/ ; }, mesh = {Humans ; Male ; *Electromyography ; Female ; *COVID-19/complications/physiopathology ; Middle Aged ; *Severity of Illness Index ; *Quality of Life ; Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Muscular Diseases/physiopathology/diagnosis ; Hand Strength/physiology ; SARS-CoV-2 ; Fatigue/physiopathology/etiology/diagnosis ; Neural Conduction/physiology ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has resulted in a post-infectious syndrome designated as long-COVID or post-COVID condition (PCC) that presents with numerous symptoms including fatigue and myalgias. This study evaluated myopathic electromyography (EMG) findings in non-hospitalized PCC patients in relation to symptom severity, quality of life (QoL), and physical function.

METHODS: Twenty-nine PCC patients with persistent symptoms ≥ 3 months after laboratory-confirmed SARS-CoV-2 infection, without hospitalization or comorbidities, were included. EMG, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed. Symptom severity was measured with visual analog scales, QoL with validated questionnaires, and physical function with the 6-min walk test, cardiopulmonary exercise testing, handgrip strength, and isokinetic dynamometry.

RESULTS: Myopathic findings on EMG were present in 62% of PCC patients (n = 18). Symptom severity (muscle pain and fatigue) and QoL (physical function and fatigue) were similar between patients with and without myopathic EMG findings. The 6-min walk test (457 ± 81 vs. 459 ± 86 m) and peak VO2 (29 ± 9 vs. 28 ± 6 mL/kg/min) were similar between patients with and without myopathic EMG findings. Handgrip strength (32 [29-43] vs. 33 [29-50] kg) and quadriceps muscle strength (136 [111-191] vs. 136 [114-184] Nm) were comparable between the groups. NCS and QST results were normal in all patients.

DISCUSSION: Myopathic findings on EMG are common in PCC patients, but no significant differences in symptom severity, QoL, or physical function were found between those with and without myopathic EMG findings. Myopathic EMG changes in PCC patients should be interpreted with caution, considering the overall clinical context.}, } @article {pmid39673054, year = {2024}, author = {Braun, S and Laemmer, C and Schulte, S and Gohlke, B}, title = {Retrospective longitudinal study on the long-term impact of COVID-19 infection on polysomnographic evaluation in patients with Prader-Willi syndrome.}, journal = {Orphanet journal of rare diseases}, volume = {19}, number = {1}, pages = {461}, pmid = {39673054}, issn = {1750-1172}, mesh = {Humans ; *Prader-Willi Syndrome/physiopathology ; *COVID-19/epidemiology ; Female ; Male ; Retrospective Studies ; Child ; *Polysomnography/methods ; Adolescent ; Longitudinal Studies ; Child, Preschool ; Young Adult ; SARS-CoV-2 ; Adult ; }, abstract = {BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) on polysomnographic evaluation in patients with Prader-Willi syndrome (PWS).

PATIENTS AND METHODS: A retrospective cohort study of two consecutive overnight polysomnograms (PSG) in 92 PWS patients (mean age 9.1, range 3.1-22 years). 57/92 participants (35 female) had a COVID-19 infection between the two consecutive examinations. 35 patients (21 female) had no infection (control group). Distribution of genetics was as follows: 13/57 (22.8%) deletion, 19/57 (33.3%) uniparental disomy, 2/57 (3,5%) imprinting defect, 3/57 (5.3%) non-deletion, 20/57 (35.1%) diagnosed by analyses of the methylation pattern of chromosome 15q11-13. Mean time interval between COVID-19 infection and post-COVID-19 evaluation was 96.2 days.

RESULTS: Course of COVID-19 infection was asymptomatic 8/82 (9.8%), mild 63/82 (76.8%), medium 11/84 (13.4%). The five most frequently experienced symptoms in PWS patients were fever (56.1%); headache (45.1%); cold (42.7%); cough (31.7%) and body aches (21.95%). PWS patients who had COVID-19 infection had significantly lower mean oxygen saturation (SpO2) measured by pulse oximetry (post 94.8% vs. pre 95.7%, p = 0.001), lower detected lowermost SpO2 (post 86.2 vs. pre 87.3%, p = 0.003), and higher occurrence of hypopnoea (post 13.9 vs. pre 10.7, p = 0.001). Time in optimal SpO2 (95-100%) decreased significantly (post 54.3% vs. pre 73.8%, p = 0.001), whereas an increase was observed in time in suboptimal SpO2 (90-95%) (post 45.5% vs. 25.8%, p = 0.001) and in time in poor SpO2 (< 90%) (post 0.7% vs. pre 0.2%, p = 0.030). Body-Mass-Index (BMI)-SDS for PWS showed no differences between the groups at any time. BMI-SDS-differences showed no influence on differences in SpO2 evaluations. In the genetic subgroup with deletion there was a statistically significant effect on an increased number of OSA (p = 0.027). The genetic subgroup with uniparental disomy (UPD) was associated with a reduced risk of higher HF (p = 0.035) and less hypopnea (p = 0.011).

CONCLUSION: PWS patients predominantly experienced only mild to medium symptoms during COVID-19 infection without necessity of hospitalisation. However, on average three months after infection, differences in PSG evaluations were still apparent, manifesting in lower SpO2 and more frequent hypopnea. A long-lasting impairment of the pulmonary system due to the COVID-19 infection might be responsible.}, } @article {pmid39673005, year = {2024}, author = {Tso, WWY and Wang, Y and Fong, DYT and Kwan, MYW and Ip, P and Chan, JFW and Leung, LK and Chan, JYK and Tsao, SSL and Chau, CSK and Yip, KM and Hui, KY and Duque, JSR and Lau, YL and Lee, TMC}, title = {Development and validation of the Post-COVID Symptom Scale for Children/Youth (PCSS-C/Y).}, journal = {European journal of pediatrics}, volume = {184}, number = {1}, pages = {81}, pmid = {39673005}, issn = {1432-1076}, support = {202111159117,//Seed Fund for Basic Research (HKU University Research Committee)/ ; 17600924//Hong Kong Research Grants Council General Research Fund (GRF)/ ; C7149-20//Hong Kong Research Grants Council Collaborative Research Fund/ ; C7060-21G//Hong Kong Research Grants Council Collaborative Research Fund/ ; }, mesh = {Humans ; Adolescent ; *COVID-19/diagnosis ; Child ; Male ; Female ; *Quality of Life ; Surveys and Questionnaires ; Young Adult ; Reproducibility of Results ; Self Report ; Psychometrics/methods ; Post-Acute COVID-19 Syndrome ; Parents/psychology ; SARS-CoV-2 ; }, abstract = {This study aims to develop and validate the Post-COVID Symptom Scale for Children/Youth (PCSS-C/Y), which is a comprehensive tool for measuring the symptom burden of post-COVID-19 conditions-persistent symptoms after SARS-CoV-2 infection, commonly known as Long COVID-and its impact on health-related quality of life among children and adolescents. Parents of children and adolescents, adolescents, and young adults with and without a history of COVID-19 were invited to fill in a questionnaire from October 2022 to June 2023. There were 386 valid parent proxy-reported responses, 433 valid adolescent self-reported responses, and 324 valid young adult self-reported responses included in the final analysis. The PCSS-C/Y demonstrated stable factor structure and good internal consistency in different sampling groups. The scale score was negatively associated with Paediatric Quality of Life Inventory (PedsQL) scores (young adult self-report, adjusted R[2] = 0.394; adolescent self-report, adjusted R[2] = 0.219; parent-report, adjusted R[2] = 0.292), while it was positively associated with Strengths and Difficulties Questionnaire (SDQ) scores (young adult self-report, adjusted R[2] = 0.195; adolescent self-report, adjusted R[2] = 0.154; parent-report, adjusted R[2] = 0.239). The scale can also discriminate the post-infected cases and control cases, Cohen's d = 0.41, 0.50, and 0.38 for adult self-report, adolescent self-report, and parent-report, respectively. Conclusions: The PCSS-C/Y is a valid and reliable tool for quantifying the diverse symptomatology of post-COVID-19 conditions in children and adolescents. It provides quantifiable measurements that enable clinicians to monitor post-COVID-19 symptoms in children and young people and facilitates the development of interventions for post-COVID-19 conditions.}, } @article {pmid39671588, year = {2024}, author = {Shao, H and Chen, H and Xu, K and Gan, Q and Chen, M and Zhao, Y and Yu, S and Li, YK and Chen, L and Cai, B}, title = {Investigating the Associations Between COVID-19, Long COVID, and Sleep Disturbances: Cross-Sectional Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e53522}, pmid = {39671588}, issn = {2369-2960}, mesh = {Humans ; *COVID-19/epidemiology/psychology/complications ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; *Sleep Wake Disorders/epidemiology ; China/epidemiology ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Surveys and Questionnaires ; Sleep Quality ; }, abstract = {BACKGROUND: COVID-19 has not only resulted in acute health issues but also led to persistent symptoms known as long COVID, which have been linked to disruptions in sleep quality.

OBJECTIVE: This study aims to investigate the associations between COVID-19, long COVID, and sleep disturbances, focusing on demographic, socioeconomic, and psychological factors among a Chinese population.

METHODS: This cross-sectional study included 1062 participants from China. Demographic, socioeconomic, and clinical data were collected through web-based questionnaires. Participants were divided into 2 groups based on COVID-19 infection status: infected and noninfected. Within the infected group, participants were further categorized into those with long COVID and those without long COVID. Noninfected participants were included in the non-long COVID group for comparison. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while depression and anxiety were evaluated using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7) scales, respectively. Multivariable linear regression was conducted to examine the associations between COVID-19, long COVID, and sleep quality, adjusting for demographic and psychosocial factors.

RESULTS: COVID-19 infection was confirmed in 857 participants, with 273 of them developing long COVID. No significant sex disparities were observed in infection rates (P=.63). However, a marginal statistical difference was noted in the prevalence of long COVID among females (P=.051). Age was significantly associated with both infection rates (P<.001) and long COVID (P=.001). Participants aged 60-70 years were particularly vulnerable to both outcomes. Sleep latency was significantly longer in the infected group (mean 1.73, SD 0.83) compared to the uninfected group (mean 1.57, SD 0.78; P=.01), and PSQI scores were higher (mean 8.52, SD 4.10 vs. 7.76, SD 4.31; P=.02). Long COVID participants had significantly worse sleep outcomes across all metrics (P<.001), except for sleep medication use (P=.17).

CONCLUSIONS: Our findings indicate that long COVID is strongly associated with significant sleep disturbances, while initial COVID-19 infection shows a more moderate association with sleep issues. Long COVID-related sleep disturbances were exacerbated by factors such as age, income, and chronic health conditions. The study highlights the need for targeted interventions that address the multifaceted impacts of long COVID on sleep, especially among vulnerable groups such as older adults and those with lower socioeconomic status. Future research should use longitudinal designs to better establish the temporal relationships and causal pathways between COVID-19 and sleep disturbances.}, } @article {pmid39671200, year = {2024}, author = {Vahratian, A and Saydah, S and Bertolli, J and Unger, ER and Gregory, CO}, title = {Prevalence of Post-COVID-19 Condition and Activity-Limiting Post-COVID-19 Condition Among Adults.}, journal = {JAMA network open}, volume = {7}, number = {12}, pages = {e2451151}, pmid = {39671200}, issn = {2574-3805}, } @article {pmid39669584, year = {2024}, author = {Li, Q and Ma, Y and He, P and Chen, D and Zhang, T and Wang, X and Xu, Y and Li, P and Wen, W and Wang, Z}, title = {Long COVID symptoms 6 months after acute infection among people living with HIV and people not living with HIV.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1430214}, pmid = {39669584}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/blood/immunology/complications ; Male ; Female ; Middle Aged ; *HIV Infections/immunology/complications/blood ; *SARS-CoV-2 ; Case-Control Studies ; Adult ; *Cytokines/blood ; Biomarkers/blood ; Antibodies, Neutralizing/blood ; Post-Acute COVID-19 Syndrome ; Intercellular Adhesion Molecule-1/blood ; }, abstract = {BACKGROUND: Chronic viral infections, such as Human Immunodeficiency Virus (HIV), and their reactivation are considered potential contributing factors to Long-Corona Virus Disease (LC). However, research on the long-term sequelae of Long-COVID in individuals with HIV is limited.

METHODS: We conducted a case-control study involving a total of 84 participants categorized into two groups: people living with HIV (PLWH) and people not living with HIV (PNLWH) within the six-month post-infection LC population. Differences in sequelae symptoms, cardiovascular biomarkers (VCAM-1, ICAM-1, and ACE2), Severe Acute Respiratory Syndrome Coronavirus 2 neutralization antibodies (SARS-CoV-2 nAb) and cytokines (IFN-γ, IL-6, and IL-17) were analyzed between the two groups.

RESULTS: After 6 months of infection, PLWH exhibited significantly higher serum levels of ACE2, VCAM-1, and ICAM-1 (P < 0.01, respectively) compared to PNLWH with COVID-19. Additionally, sequelae symptoms were more pronounced in PNLWH, and there were no differences in serum levels of IFN-γ, TNF-α, IL-6, and IL-17 between the two groups (P > 0.05, respectively).

CONCLUSION: PLWH had lower symptoms of LC and reduced frequency of symptoms, increased cardiovascular risk factors, and no differences in levels of inflammation or SARS-CoV-2 nAb levels when compared to PNLWH.}, } @article {pmid39667631, year = {2024}, author = {Couto Amendola, F and Roncete, G and Aguiar Monteiro Borges, S and Castanho de Almeida Rocca, C and de Pádua Serafim, A and Salim de Castro, G and Seelaender, M and Constantino Miguel, E and Busatto Filho, G and Forlenza, OV and Furlan Damiano, R}, title = {A Two-Year cohort study examining the impact of cytokines and chemokines on cognitive and psychiatric outcomes in Long-COVID-19 patients.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.12.006}, pmid = {39667631}, issn = {1090-2139}, abstract = {This study investigates the relationship between clinical, sociodemographic, and neuropsychological symptoms and serum cytokine concentrations with long-term cognitive and psychiatric outcomes in long-COVID-19 patients. We reassessed 108 adults who survived moderate to severe COVID-19 at two intervals post-discharge (T1, mean 6.9 months; T2, mean 23.5 months). Baseline sociodemographic and clinical data were collected from hospital records, while cognitive and mental health assessments included psychometric tests such as the Hospital Anxiety and Depression Scale (HADS) and Immediate and Delayed Recall Tests from the CERAD Battery. Serum cytokine levels were measured at T1. Generalized Additive Models (GAMs), Elastic Net Regression (NET), and Psychological Network Analysis (PNA) were used to analyze the data. The GAM analysis revealed significant associations between acute COVID-19 severity and Epworth Sleepiness Score with persistent anxiety symptoms at T2. For depression, both WHO severity class and Eotaxin levels were significant predictors. The Anti-inflammatory Index showed a marginally significant relationship with immediate recall, while age was marginally associated with delayed recall performance. In NET, only anxiety was significantly associated with Epworth Sleepiness Score, WHO severity class, and Proinflammatory Index. PNA did not reveal direct connections between cytokines and neuropsychological outcomes in the graphical model. However, centrality measures indicated that the Proinflammatory Index and VEGF were more central within the network, suggesting they might be important components of the overall system. This study provides insights into the complex role of cytokines and inflammation in long-COVID-19 outcomes, potentially aiding in the identification of biomarkers for diagnosis and prognosis.}, } @article {pmid39667587, year = {2025}, author = {Romanet, C and Wormser, J and Cachanado, M and Santiago, MG and Chatellier, G and Valenza, MC and Philippart, F}, title = {Effectiveness of physiotherapy modalities on persisting dyspnoea in long COVID: A systematic review and meta-analysis.}, journal = {Respiratory medicine}, volume = {236}, number = {}, pages = {107909}, doi = {10.1016/j.rmed.2024.107909}, pmid = {39667587}, issn = {1532-3064}, mesh = {Adult ; Humans ; *Dyspnea/etiology/psychology/therapy ; *Physical Therapy Modalities ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {BACKGROUND: Dyspnoea is often found months and years later in the "long-covid" syndrome, impairing quality of life and further perpetuating anxiety and post-traumatic stress disorders. Physiotherapy was recommended as a treatment in long-covid, but there is still insufficient evidence on its effectiveness.

METHODS: We conducted a systematic literature search on MEDLINE, PEDro, WOS, Scopus, VHL and the Cochrane Library until July 2023 (PROSPERO registration number: CRD42023427464). We selected comparative trials including adults with persistent breathlessness following COVID-19, regardless of the initial severity, for whom physiotherapy was implemented as a treatment for dyspnoea. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the PEDro Scale.

RESULTS: 19 studies that included 1292 adults fulfilled the inclusion criteria, of which 15 were randomised controlled trials and 4 non-randomised controlled trials. As for the rehabilitation modalities, 6 studies used respiratory muscle training, 6 studies used low to moderate intensity rehabilitation, 6 used high intensity rehabilitation and one used passive rehabilitation. The methods used between and within each group differed greatly, leading to an expected high heterogeneity of results. Nethertheless the random-effects model found a significant difference favouring physiotherapy (SMD -0.63, 95 CI [-1.03; -0.24], p < 0.001, I[2] = 88 %). Subgroup analysis showed a significant effect in the high intensity rehabilitation group alone, with null heterogeneity.

CONCLUSION: In people suffering from dyspnoea following a SARS-CoV-2 infection, physiotherapy and especially pulmonary rehabilitation may help alleviate respiratory symptoms. Future studies will need to provide more consistent rehabilitation methods and better descriptions of them so as to reveal clear effects and avoid the confusion caused by using too many rehabilitation modalities.}, } @article {pmid39667116, year = {2024}, author = {Niemczak, CE and Ford, JC and Roth, RM and Leigh, SM and Parsonnet, J and Martin, C and Soule, SO and Haron, TM and Buckey, JC and Wylie, GR}, title = {Neuroimaging markers of cognitive fatigue in individuals with post-acute sequelae of SARS-CoV-2 infection.}, journal = {Brain and cognition}, volume = {183}, number = {}, pages = {106254}, doi = {10.1016/j.bandc.2024.106254}, pmid = {39667116}, issn = {1090-2147}, support = {L30 DC020601/DC/NIDCD NIH HHS/United States ; }, abstract = {Persistent cognitive fatigue (CF) is the most reported symptom in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), but little is known about its underlying neural basis. This pilot study examined fMRI brain activation patterns during a fatiguing task in those with and without PASC. We hypothesized that individuals with PASC would show changes in CF-related brain activation within fatigue network. Participants were 10 adults with PASC and persistent CF and 10 age- and gender-matched healthy controls. The 2-back working memory task was used during fMRI to induce CF. Patients with PASC reported greater CF, as measured using a Visual Analogue Scale of Fatigue (VAS-F), throughout the task. The relationship of brain activation in the fatigue network to increased CF during the fatiguing task did not differ between groups. There were, however, more areas inside and outside the fatigue network that were activated in the PASC group as reported CF increased. The relationship between brain activation and scores on the 2-back did differ between groups, with the PASC group showing more frontal activation. Findings suggest that individuals with PASC and CF may need to exert greater mental effort during demanding cognitive tasks, reflected in recruitment of a broader network of brain regions.}, } @article {pmid39665720, year = {2024}, author = {Brahimi, N and Croitoru, D and Saidoune, F and Zabihi, H and Gilliet, M and Piguet, V}, title = {From Viral Infection to Skin Affliction: Unveiling Mechanisms of Cutaneous Manifestations in COVID-19 and Post-COVID Conditions.}, journal = {The Journal of investigative dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jid.2024.03.047}, pmid = {39665720}, issn = {1523-1747}, abstract = {COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses. We will also review the emerging insights into post-COVID conditions (also termed long COVID) and how they may be implicated in the persistence of COVID-19-associated skin diseases.}, } @article {pmid39664544, year = {2024}, author = {Li, B and Zhou, Y and Zhang, T and Ma, A and Hao, W}, title = {Effectiveness of a scenario-based, community-based intervention in containing COVID-19 in China.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1449305}, pmid = {39664544}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; China/epidemiology ; *SARS-CoV-2 ; Pandemics/prevention & control ; }, abstract = {BACKGROUND: Given the significant impact of the more than three-year-long COVID-19 pandemic on people's health, social order, and economic performance, as well as the potential re-emergence of a new variant and the epidemic "Disease X," it is crucial to examine its developmental trends and suggest countermeasures to address community epidemics of severe respiratory infectious diseases.

METHODS: The epidemiological characterization of various strains of COVID-19 was modeled using an improved Susceptible-Exposed-Infectious-Recovered (SEIR) model to simulate the infections of different strains of COVID-19 under different scenarios, taking as an example an urban area of a prefecture-level city in Shandong Province, China, with a resident population of 2 million. Scenarios 1-5 are scenario-based simulations the Omicron strain, and 6-8 simulate the original COVID-19 strain, with different parameters for each scenario. Scenarios 1 and 6 do not consider community NPIs and represent natural epidemic scenarios. Scenarios 2-4 assess the impact of different NPIs on the original COVID-19 strain. Scenarios 1-4 and 6-8 compare the effects of the same measures on different strains. Scenario 5 simulates the effects of implementing NPIs after an outbreak has spread widely. Compare scenarios 4 and 9 to analyze the effect of high grades versus dynamic clearing of NPIs. By analyzing the time at which the peak number of cases was reached and the maximum number of cases, we were able to calculate the effectiveness of urban community control measures (NPIs) and the impact of vaccination on disease trends. Based on our research into the degree of restriction of social activities in different levels of control areas during real-world epidemics, we categorized the NPIs into three levels, with controls becoming increasingly stringent from levels 1 to 3 as low-, medium-, and high-risk areas are, respectively, controlled.

RESULTS: In simulation scenarios 1-5 and 9, where the epidemic strain is Omicron and the susceptible population receives three doses of vaccine, it was found that the real-time peak number of cases in scenario 2, which implemented level 1 controls, was reduced by 18.19%, and in scenario 3, which implemented level 2 controls, it was reduced by 38.94%, compared with scenario 1, where no control measures were taken. Level 1 and level 2 controls do not block transmission but significantly reduce peak incidence and delay the peak time. In scenario 5, even with a high number of initial cases, the implementation of level 3 controls can still control the outbreak quickly, but it requires a longer period of time. However, Omicron has a low rate of severe illness, and the existing beds in City A could largely cope even if the control measures had not been implemented. Analyzing scenarios 4 and 9, level 3 community control and dynamic zeroing of the three zones were similarly successful in interrupting the spread of the epidemic. In simulation scenarios 6-8, where the prevalent strain was the original COVID-19 strain, only level 3 community control was able to rapidly extinguish the outbreak. Unchecked, the outbreak is severe, characterized by high peaks and substantial medical stress. Although level 2 controls reduced real-time incidence and peak new infections by 39.81 and 61.33%, and delayed the peaks by 55 and 52 days, respectively, the high rate of severe illnesses may still overwhelm the medical system.

CONCLUSION: Control effects are related to the level, timing and virus characteristics. Level 3 and dynamic zeroing measures can interrupt community transmission in the early stages of an outbreak. During a pandemic, different NPIs must be implemented, considering the virus's status and cost of control, and ensuring that medical resources are sufficient to maintain medical order.}, } @article {pmid39664211, year = {2024}, author = {}, title = {Correction to: Long Covid-a cause of concern for surgical training.}, journal = {Journal of hip preservation surgery}, volume = {11}, number = {3}, pages = {233}, doi = {10.1093/jhps/hnae023}, pmid = {39664211}, issn = {2054-8397}, abstract = {[This corrects the article DOI: 10.1093/jhps/hnac039.].}, } @article {pmid39663632, year = {2024}, author = {Batool-Anwar, S and Fashanu, OS and Quan, SF}, title = {Long-term Effects of COVID-19 on Sleep Patterns.}, journal = {Thoracic research and practice}, volume = {1}, number = {1}, pages = {}, doi = {10.5152/ThoracResPract.2024.24013}, pmid = {39663632}, issn = {2979-9139}, abstract = {To examine the long-term impact of Coronavirus Disease 2019 (COVID-19) on sleep patterns and prevalence of sleep disorders and to increase public health awareness of long COVID. MATERIAL AND Using the centralized Massachusetts General Brigham Research Patient Data Registry (RPDR), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications was obtained through chart review. Two hundred forty-six completed surveys were analyzed. The average age was 53.3 ± 16.3 years, and participants were predominantly non-Hispanic White (84.1%) and female (74.3%). The average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion were non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating sleep (39 ± 49% vs 31 ± 46% prior to COVID infection, P = .01). Similarly, the participants reported difficulty maintaining sleep after COVID infection (57% vs 43% prior to infection P < .001). Additionally, there was an increase in the use of sleep aids (30% vs 24% before the infection, P = .003). The participants also reported a decrease in feeling rested and an increase in the need for napping (58% vs. 36%, P < .0001) and (27% vs. 40%, P < .0001), respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants. Infection by SARS-CoV-2 was shown to have negative effects on sleep, and a significant proportion of adults experienced insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.}, } @article {pmid39663173, year = {2024}, author = {Thomas, B and Pattinson, R and Edwards, D and Dale, C and Jenkins, B and Lande, H and Bundy, C and Davies, J}, title = {Defining and measuring long COVID fatigue: a scoping review.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e088530}, pmid = {39663173}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/complications ; *Fatigue/etiology/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Long COVID encompasses a range of symptoms in which fatigue is one of the most prevalents. It is clear from other conditions that the definition and measurement of fatigue can be complex, but it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.

DESIGN: Scoping review following JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews.

DATA SOURCES: Medline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertation & Theses Database were searched from January 2020 to May 2023.

ELIGIBILITY CRITERIA: This review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.

DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the title, abstracts and full texts of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.

RESULTS: The search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were identified: 21 self-report measures (eg, Fatigue Assessment Scale) and five fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in force generating capacity of a muscle).

CONCLUSIONS: The definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which were problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.

REVIEW REGISTRATION: The protocol has been registered on open science framework (https://doi.org/10.17605/OSF.IO/HNF8Z).}, } @article {pmid39662824, year = {2024}, author = {Górska, A and Canziani, LM and Rinaldi, E and Pana, ZD and Beale, S and Bai, F and Boxma-de Klerk, BM and de Bruijn, S and Donà, D and Ekkelenkamp, MB and Incardona, F and Mallon, P and Marchetti, GC and Puhan, M and Riva, A and Simensen, VC and Vaillant, M and van der Zalm, MM and van Kuijk, SMJ and Wingerden, SV and Judd, A and Tacconelli, E and Peñalvo, JL}, title = {Learning from post-COVID-19 condition for epidemic preparedness: a variable catalogue for future post-acute infection syndromes.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.12.001}, pmid = {39662824}, issn = {1469-0691}, abstract = {SCOPE: The emergence of post-COVID-19 condition (PCC) after SARS-CoV-2 infection underscores the critical need for preparedness in addressing future post-acute infection syndromes (PAIS), particularly those linked to epidemic outbreaks. The lack of standardized clinical and epidemiological data during the COVID-19 pandemic has significantly hindered timely diagnosis and effective treatment of PCC, highlighting the necessity of pre-emptively standardizing data collection in clinical studies to better define and manage future PAIS. In response, the Cohort Coordination Board, a consortium of European-funded COVID-19 research projects, has reviewed data from PCC studies conducted by its members. This paper leverages the Cohort Coordination Board's expertise to propose a standardized catalogue of variables, informed by the lessons learned during the pandemic, intended for immediate use in the design of future observational studies and clinical trials for emerging infections of epidemic potential.

RECOMMENDATIONS: The early implementation of standardized data collection, facilitated by the PAIS data catalogue, is essential for accelerating the identification and management of PAIS in future epidemics. This approach will enable more precise syndrome definitions, expedite diagnostic processes, and optimize treatment strategies, while also supporting long-term follow-up of affected individuals. The availability of harmonized data collection protocols will enhance preparedness across European and international cohort studies, and trials enabling a prompt and coordinated response, as well as more efficient resource allocation, in the event of emerging infections and associated PAIS.}, } @article {pmid39662181, year = {2024}, author = {Wang, Y and Alcalde-Herraiz, M and Güell, KL and Chen, L and Mateu, L and Li, C and Ali, R and Wareham, N and Paredes, R and Prieto-Alhambra, D and Xie, J}, title = {Refinement of post-COVID condition core symptoms, subtypes, determinants, and health impacts: a cohort study integrating real-world data and patient-reported outcomes.}, journal = {EBioMedicine}, volume = {111}, number = {}, pages = {105493}, pmid = {39662181}, issn = {2352-3964}, abstract = {BACKGROUND: Post-COVID-19 condition (PCC) affects millions of people, and is an essential component of the long-term impact of COVID-19 during the post-pandemic era. Yet, consensus on clinical case definition and core components of PCC remains lacking, affecting our ability to inform research and evidence-based management. Our study aims 1) to identify the most specific symptoms for PCC, and identify clinical subtypes; 2) to evaluate both virus- and host-related determinants of PCC, and 3) assess the impact of PCC on physical and mental health.

METHODS: We studied participants from UK Biobank who completed a health and wellbeing survey between June and September 2022. Participants reported the current conditions of the presence, duration, and functional limitations of 45 symptoms, using an online questionnaire designed specifically for COVID-19 research. SARS-CoV-2 infection status and disease history were obtained through linkage to surveillance data and electronic medical records, respectively. Participants reporting symptoms within 30 days after infection (acute phase) were excluded. The most specific PCC symptoms were defined using two criteria: statistical significance (P < 0.05 after Bonferroni correction) and clinical relevance (absolute risk increase > 5%). Propensity score weighting was used to control for confounding. Subtypes of PCC were then defined based on the specific symptoms among the COVID-19 infected individuals. A multivariable regression was used to study pathogen- and host-related risk factors for PCC, and its impact on 13 physical and 4 mental health patient-reported functional outcomes.

FINDINGS: 172,303 participants (mean age 68.9, 57.4% female) were included in the analysis, of whom 43,395 had PCR-confirmed COVID-19. We identified 10 most specific symptoms and classified four PCC subtypes: ENT subtype (30.1%), characterized by alterations in smell, taste, and hearing loss; cardiopulmonary subtype (10.4%), characterized by shortness of breath, postural tachycardia, chest tightness, and chest pressure; neurological subtype (23.5%), characterized by brain fog and difficulty speaking; and general fatigue subtype (38.0%), characterized by mild fatigue. A higher PCC risk was observed for patients with Wild-type variant, multiple infections, and severe acute COVID-19 illness, consistently across the four PCC subtypes. In addition, a range of factors, including socioeconomic deprivation, higher BMI, unhealthy lifestyle, and multiple chronic health conditions, were associated with increased PCC risk, except for age and sex. Conversely, vaccination was associated with a largely reduced PCC risk, particularly for the cardiopulmonary subtypes. Individuals with PCC experienced a much worse physical and mental health. Specifically, the cardiopulmonary subtype had the most pronounced adverse impact on function impairments, followed by neurological, mild fatigue, and ENT subtype. The most affected functions included the ability to concentrate, participate in day-to-day work, and emotional vulnerability to health problems.

INTERPRETATION: PCC can be categorized into four distinct subtypes based on ten core symptoms. These subtypes appeared to share a majority of pathogen and host-related risk factors, but their impact on health varied markedly by subtype. Our findings could help refine current guidelines for precise PCC diagnosis and progression, enhance the identification of PCC subgroups for targeted research, and inform evidence-based policy making to tackle this new and debilitating condition.

FUNDING: NIHR Senior Research Fellowship (grant SRF-2018-11-ST2-004).}, } @article {pmid39661840, year = {2024}, author = {Rebouças, ERN and Ramos, TR and Sousa, BG and Costa, RFD and Gouveia, SSV and Silva, IC and Mont'Alverne, DGB and Campos, NG}, title = {Long COVID: a cross-sectional study of respiratory muscle strength, lung function, and persistent symptoms at one year after hospital discharge.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {50}, number = {5}, pages = {e20240246}, pmid = {39661840}, issn = {1806-3756}, } @article {pmid39660133, year = {2024}, author = {O'Niel, A and Pederson, A and Saltontall, E and Nguyen, K and Pantoja, M and Chaudhari, M and Sandholm, P and Yoon, E and Harrison, HF and Boutros, S and Hirsch, AJ and Raber, J}, title = {Effects of COVID-19 virus-like particles on the behavioral and cognitive performance of human apolipoprotein E targeted replacement mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1473366}, pmid = {39660133}, issn = {1664-3224}, support = {R21 AG065914/AG/NIA NIH HHS/United States ; R21 AG079158/AG/NIA NIH HHS/United States ; RF1 AG059088/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Mice ; Humans ; *COVID-19 ; *SARS-CoV-2/physiology ; *Apolipoproteins E/genetics ; Cognition ; Behavior, Animal ; Mice, Transgenic ; Male ; Disease Models, Animal ; Female ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; }, abstract = {INTRODUCTION: The effects of viral infections might be apolipoprotein E (apoE) isoform-dependent. In humans, there are three major apoE isoforms, E2, E3, and E4. E4 is associated with the enhanced entry of several viruses into the brain and their disease progression. A concern of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the development of post-acute COVID-19 syndrome, also known as long COVID. Genetic risk factors for developing long COVID were reported.

METHODS: In this study, we used virus-like particles (VLPs) that include expression of the SARS-CoV-2 nucleocapsid (N), membrane (M), and envelope (E) structural proteins together with S. In the current study, we used human E2, E3, and E4 targeted replacement mice to assess whether these VLPs affect body weight, behavioral and cognitive performance, and circadian body temperatures. Using VLPs allow working outside an ABSL-3 facility.

RESULTS: The effects of VLPs on some behavioral measures were apoE isoform-dependent, with the E2 mice being more affected than E3 or E4 mice. The overall decreased activity in the open field containing objects in week 2 indicate that VLPs can also reduce activity levels in an apoE isoform-independent fashion.

DISCUSSION: The results of the current study indicate that even in the absence of viral replication, detrimental effects of VLPs on behavioral measures and circadian body temperatures are seen.}, } @article {pmid39660101, year = {2025}, author = {Toussaint, A and Weigel, A and Löwe, B and , }, title = {The overlooked burden of persistent physical symptoms: a call for action in European healthcare.}, journal = {The Lancet regional health. Europe}, volume = {48}, number = {}, pages = {101140}, pmid = {39660101}, issn = {2666-7762}, abstract = {Regardless of their cause, persistent physical symptoms are distressing somatic complaints that occur on most days for at least several months. They are common in patients with somatic diseases, functional somatic disorders, mental disorders, and undiagnosed medical conditions and are often associated with significant impairment and medical costs. Despite their prevalence and impact, persistent physical symptoms are often overlooked in medical care. This Personal View stresses the importance of recognising persistent physical symptoms as a European health issue. It advocates improvements in research, clinical management, public health, and policy. Efforts should prioritise integrating models of symptom perception and biopsychosocial perspectives into medical care and education, fostering interdisciplinary collaboration, and developing standardised guidelines to enhance patient care, reduce stigma, and improve clinical outcomes. Increased research funding can accelerate progress in understanding and effectively managing persistent physical symptoms. Addressing these priorities will support patients and healthcare professionals, ensuring adequate care and a higher quality of life for affected individuals.}, } @article {pmid39659735, year = {2024}, author = {McNaughton, CD and Austin, PC and Li, Z and Sivaswamy, A and Fang, J and Abdel-Qadir, H and Udell, JA and Wodchis, WP and Lee, DS and Mostarac, I and Atzema, CL}, title = {Higher Post-Acute Health Care Costs Following SARS-CoV-2 Infection Among Adults in Ontario, Canada.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {5749-5761}, pmid = {39659735}, issn = {1178-2390}, abstract = {PURPOSE AND INTRODUCTION: Growing evidence suggests SARS-CoV-2 infection increases the risk of long term cardiovascular, neurological, and other effects. However, post-acute health care costs following SARS-CoV-2 infection are not known.

Beginning 56 days following SARS-CoV-2 polymerase chain reaction (PCR) testing, we compared person-specific total and component health care costs (2020 CAD$) for the first year of follow-up at the mean and 99[th] percentiles of health care costs for matched test-positive and test-negative adults in Ontario, Canada, between January 1, 2020, and March 31, 2021. Matching included demographics, baseline clinical characteristics, and two-week time blocks.

RESULTS: For 531,182 people, mean person-specific total health care costs were $513.83 (95% CI $387.37-$638.40) higher for test-positive females and $459.10 (95% CI $304.60-$615.32) higher for test-positive males, which were driven by hospitalization, long-term care, and complex continuing care costs. At the 99[th] percentile of each subgroup, person-specific health care costs were $12,533.00 (95% CI $9008.50-$16,473.00) higher for test-positive females and $14,604.00 (95% CI $9565.50-$19,506.50) for test-positive males, driven by hospitalization, specialist (males), and homecare costs (females). Cancer costs were lower. Six-month and 1-year cost differences were similar.

CONCLUSION: Post-acute health care costs after a positive SARS-CoV-2 PCR test were significantly higher than matched test-negative individuals, and these increased costs persisted for at least one year. The largest increases health care costs came from hospitalizations, long-term care, complex continuing care, followed by outpatient specialists (for males) and homecare costs (for women). Given the magnitude of ongoing viral spread, policymakers, clinicians, and patients should be aware of higher post-acute health care costs following SARS-CoV-2 infection.}, } @article {pmid39659719, year = {2024}, author = {Tai, Y and Jain, N and Kim, G and Husain, FT}, title = {Tinnitus and COVID-19: effect of infection, vaccination, and the pandemic.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1508607}, pmid = {39659719}, issn = {2296-2565}, mesh = {Humans ; *Tinnitus/etiology/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; *SARS-CoV-2 ; COVID-19 Vaccines/administration & dosage ; Surveys and Questionnaires ; Aged ; Risk Factors ; Vaccination/statistics & numerical data ; Pandemics ; Hearing Loss/epidemiology/etiology ; Self Report ; }, abstract = {INTRODUCTION: The COVID-19 pandemic, which began worldwide around March 2020, has had an impact on hearing health, specifically tinnitus and hearing loss. Physiologically, COVID-19 infection, or medication used to treat the infection, has been reported to be a potential risk factor for tinnitus onset. In addition, tinnitus was reported to be a long COVID symptom or to occur after a COVID-19 vaccination in some cases. With most reports focused on the clinical population, this study aimed to investigate how the onset of tinnitus is associated with COVID-19 infection, long COVID, and COVID-19 vaccination in the general population based on self-report, while accounting for otologic and psychological symptoms.

METHODS: In this study, a cross-sectional online survey that included general demographic questions, questions about tinnitus, hearing loss, hyperacusis, emotional status, and the Tinnitus Functional Index (TFI) was conducted.

RESULTS: Completed survey data of 1,511 respondents who reported having tinnitus or believed to have COVID-associated tinnitus were included in the analysis. Participants were categorized into four groups based on their judgment regarding the etiology of their tinnitus: (1) COVID infection group, (2) long COVID group, (3) COVID vaccination group, and (4) pre-existing tinnitus group. The results suggest that tinnitus severity (estimated using TFI scores) was significantly lower in the pre-existing tinnitus group than in any of the COVID-associated tinnitus groups. While varying factors were found to contribute to tinnitus severity among the COVID-associated groups, overall, depression and/or anxiety accounted for the most variance in predicting tinnitus severity.

DISCUSSION: The findings highlight the need to evaluate the impact of varying otologic and psychological symptoms in individuals with COVID-associated tinnitus for better patient-centered care.}, } @article {pmid39659228, year = {2024}, author = {Zheng, C and Yu, FY and Chan, PS and Sun, F and Chen, XK and Huang, WY and Wong, SH and Fang, Y and Wang, Z}, title = {Receiving three doses of inactivated or mRNA COVID-19 vaccines was associated with lower odds of long COVID symptoms among people with a history of SARS-CoV-2 infection in Hong Kong, China: a cross-sectional survey study.}, journal = {Epidemiology and infection}, volume = {152}, number = {}, pages = {e166}, pmid = {39659228}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Hong Kong/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Adult ; Middle Aged ; *COVID-19 Vaccines/administration & dosage ; *Vaccines, Inactivated/administration & dosage ; Young Adult ; *SARS-CoV-2/immunology ; Aged ; Adolescent ; mRNA Vaccines ; }, abstract = {High prevalence of long COVID symptoms has emerged as a significant public health concern. This study investigated the associations between three doses of COVID-19 vaccines and the presence of any and ≥3 types of long COVID symptoms among people with a history of SARS-CoV-2 infection in Hong Kong, China. This is a secondary analysis of a cross-sectional online survey among Hong Kong adult residents conducted between June and August 2022. This analysis was based on a sub-sample of 1,542 participants with confirmed SARS-CoV-2 infection during the fifth wave of COVID-19 outbreak in Hong Kong (December 2021 to April 2022). Among the participants, 40.9% and 16.1% self-reported having any and ≥3 types of long COVID symptoms, respectively. After adjusting for significant variables related to sociodemographic characteristics, health conditions and lifestyles, and SARS-CoV-2 infection, receiving at least three doses of COVID-19 vaccines was associated with lower odds of reporting any long COVID symptoms comparing to receiving two doses (adjusted odds ratio [AOR]: 0.69, 95% CI: 0.54, 0.87, P = .002). Three doses of inactivated and mRNA vaccines had similar protective effects against long COVID symptoms. It is important to strengthen the coverage of COVID-19 vaccination booster doses, even in the post-pandemic era.}, } @article {pmid39658729, year = {2024}, author = {Treadwell, JR and Wagner, J and Reston, JT and Phillips, T and Hedden-Gross, A and Tipton, KN}, title = {Treatments for Long COVID autonomic dysfunction: a scoping review.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {}, number = {}, pages = {}, pmid = {39658729}, issn = {1619-1560}, support = {MSA-SOW#06-ECRI-ENG-10-02-2023/PCORI/Patient-Centered Outcomes Research Institute/United States ; }, abstract = {PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guidelines, and unpublished/ongoing studies.

METHODS: We first interviewed 11 stakeholders (clinicians, clinician/researchers, payors, patient advocates) to gain clinical insights and identify key areas of focus. We searched Embase, CINAHL, Medline, PsycINFO, and PubMed databases for relevant English-language articles published between 1 January 2020 and 30 April 2024. We also searched several other resources for additional relevant guidelines (e.g., UpToDate) and unpublished/ongoing studies (e.g., the International Clinical Trials Registry Platform). All information was summarized narratively.

RESULTS: We included 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a nutraceutical (SIM01) on fatigue and gastrointestinal upset. The 11 guidelines and position statements addressed numerous aspects of treatment, but primarily exercise/rehabilitation, fluid/salt intake, and the use of compression garments. The 15 unpublished/ongoing studies are testing nine different interventions, most prominently ivabradine and intravenous immunoglobulin.

CONCLUSION: Existing studies on the treatment of Long COVID autonomic dysfunction are often small and uncontrolled, making it unclear whether the observed pre-post changes were due solely to the administered treatments. Guidelines display some overlap, and we identified no direct contradictions. Unpublished/ongoing studies may shed light on this critical area of patient management.}, } @article {pmid39657791, year = {2024}, author = {Beams, AB and Earn, DJD and Colijn, C}, title = {Uncertainty in COVID-19 transmission could undermine our ability to predict long COVID.}, journal = {Journal of the Royal Society, Interface}, volume = {21}, number = {221}, pages = {20240438}, pmid = {39657791}, issn = {1742-5662}, support = {//Canadian Institutes of Health Research (CIHR) Grant 2021-2024/ ; //Natural Sciences and Engineering Research Council of Canada (NSERC) Grant/ ; }, mesh = {Humans ; *COVID-19/transmission/epidemiology/prevention & control/immunology ; *SARS-CoV-2/immunology ; Uncertainty ; Post-Acute COVID-19 Syndrome ; Pandemics ; Models, Theoretical ; COVID-19 Vaccines/therapeutic use/immunology ; }, abstract = {As SARS-CoV-2 has transitioned from a novel pandemic-causing pathogen into an established seasonal respiratory virus, focus has shifted to post-acute sequelae of COVID-19 (PASC, colloquially 'long COVID'). We use compartmental mathematical models simulating emergence of new variants to help identify key sources of uncertainty in PASC trajectories. Some parameters (such as the duration and equilibrium prevalence of infection, as well as the fraction of infections that develop PASC) matter more than others (such as the duration of immunity and secondary vaccine efficacy against PASC). Even if newer variants carry the same risk of PASC as older types, the dynamics of selection can give rise to greater PASC prevalence. However, identifying plausible PASC prevalence trajectories requires accurate knowledge of the transmission potential of COVID-19 variants in the endemic phase. Precise estimates for secondary vaccine efficacy and duration of immunity will not greatly improve forecasts for PASC prevalence. Researchers involved with Living Evidence Synthesis, or other similar initiatives focused on PASC, are well advised to ascertain primary efficacy against infection, duration of infection and prevalence of active infection in order to facilitate predictions.}, } @article {pmid39657574, year = {2024}, author = {Fernández-García, JM and Romero-Secin, A and Rubín-García, M}, title = {[Association between obesity and Long-Covid: A narrative review].}, journal = {Semergen}, volume = {51}, number = {3}, pages = {102390}, doi = {10.1016/j.semerg.2024.102390}, pmid = {39657574}, issn = {1578-8865}, abstract = {To analyze the evidence in the scientific literature that relates Long-Covid and obesity, a narrative review of articles published in English and Spanish in Medline and Embase in the last 5years has been carried out. Infection with the SARS-CoV-2 virus causes a systemic inflammatory state increasing nutritional demand that favors sarcopenia in Long-Covid syndrome. It also causes endothelial dysfunction and a prothrombotic state that favors the formation of microthrombi and tissue hypoxia. A healthy and balanced diet is essential to treat obesity in addition to modifying the microbiota in Long-Covid and promoting physical and mental well-being. Obesity is an independent risk factor that increases the need for hospitalization, cardiovascular risk and mortality, as well as susceptibility to Long-Covid. Adipose tissue is a good reservoir of the virus, enhancing the comorbidities associated with obesity (high blood pressure, diabetes mellitus, dyslipidemia or fatty liver). There is insufficient evidence to recommend nutritional supplements to improve Long-Covid symptoms.}, } @article {pmid39655430, year = {2024}, author = {West, J and Kwan, ATH and Teopiz, KM and Guo, Z and Le, GH and Badulescu, S and Rhee, TG and Wong, S and Cao, B and Ho, R and Rosenblat, JD and Mansur, RB and Phan, L and Subramaniapillai, M and McIntyre, RS}, title = {Impact of depressive symptoms on motivation in persons with post-COVID-19 condition.}, journal = {CNS spectrums}, volume = {}, number = {}, pages = {1-5}, doi = {10.1017/S1092852924000440}, pmid = {39655430}, issn = {1092-8529}, support = {//H. Lundbeck A/S/ ; }, abstract = {OBJECTIVE: The World Health Organization (WHO) has defined Post-COVID-19 Condition (PCC) as the onset of symptoms within three months after resolution of an acute SARS-CoV-2 infection, wherein symptoms persist for at least two months and cannot be explained by another medical/psychiatric condition. Persons living with PCC report debilitating symptoms including, but not limited to, depressive symptoms and motivational deficits. The aim of this post-hoc analysis was to evaluate the association between depressive symptoms and motivation in adults with PCC.

METHODS: We conducted a post-hoc analysis of an 8-week, double-blind, randomized, placebo-controlled trial evaluating adults (18 years or older) in Canada with WHO-defined PCC and cognitive symptoms. This post-hoc analysis is comprised of baseline data that evaluates the association between depressive symptom severity measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) and motivational systems measured by the Behavioral Inhibition System/Behavioral Activation System Questionnaire (BIS/BAS).

RESULTS: There was a statistically significant association between depressive symptoms and BIS (β = -0.041 95% CI [-0.066, -0.016], p<0.05), BAS reward responsiveness (β = 0.043 95% CI [0.012, 0.074], p<0.05), sex (β = -0.137 95% CI [-0.266, -0.008], p<0.05), and confirmed COVID-19 infection (β = 0.196 95% CI [0.061, 0.332], p<0.05).

CONCLUSIONS: Depressive symptoms were associated with motivational deficits in persons living with PCC. Optimizing treatment for depressive symptoms may potentially improve aspects of motivational impairment amongst persons with PCC. All patients presenting with MDD and a history of COVID-19 infection should be assessed for the presence of PCC.}, } @article {pmid39655234, year = {2024}, author = {Chadda, KR and Roberts, SA and Lugg, ST and Faniyi, AA and Faustini, SE and Webster, C and Duffy, JE and Hewison, M and Shields, A and Richter, AG and Parekh, D and Scott, A and Thickett, DR}, title = {Vitamin D deficiency and duration of COVID-19 symptoms in UK healthcare workers.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1494129}, pmid = {39655234}, issn = {2296-858X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {OBJECTIVES: Vitamin D has a role in the innate immunity against pathogens and is also involved in mechanisms for reducing inflammation. VD deficiency (VDD) may increase COVID-19 infection susceptibility, however research is limited on the association between VDD and COVID-19 symptom prevalence and duration. The study aimed to determine whether VDD is a risk factor for the presence and extended duration of COVID-19 symptoms.

METHODS: Data was analyzed from NHS healthcare workers who isolated due to COVID-19 symptoms as a part of the COVID-19 convalescent immunity study between 12th to 22nd May 2020. Participants self-reported the presence and duration of viral symptoms. Anti-SARS-CoV-2 antibodies and vitamin D (25(OH)D3) serum levels were measured on day of recruitment. VDD was defined as 25(OH)D3 levels of < 30 nmol/l.

RESULTS: Of the 392 participants, 15.6% (n = 61) had VDD. VDD participants had more symptoms overall (p = 0.0030), including body aches (p = 0.0453), and extended duration of body aches (p = 0.0075) and fatigue (p = 0.0127). Binary logistic regression found that both VDD (OR 3.069, 95% CI 1.538-6.124; p = 0.001) and age (OR 1.026, 95% CI 1.003-1.049; p = 0.025) were independently associated with extended durations of body aches. VDD (OR 2.089, 95% CI 1.087-4.011; p = 0.027), age (OR 1.036, 95% CI 1.016-1.057; p < 0.001) and seroconversion (OR 1.917, 95% CI 1.203-3.056; p = 0.006), were independently associated with extended durations of fatigue.

CONCLUSION: VDD is a significant independent risk factor for extended durations of body aches and fatigue in healthcare workers who isolated for COVID-19 viral symptoms. Vitamin D supplementation may reduce symptom duration and is thus an area for future research.}, } @article {pmid39654800, year = {2024}, author = {Li, R and Liu, W and Liu, D and Jin, X and Wang, S}, title = {The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {5}, number = {}, pages = {1486851}, pmid = {39654800}, issn = {2673-561X}, abstract = {In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues.}, } @article {pmid39653343, year = {2024}, author = {Gupte, A and Sriram, S and Gunasekaran, V and Chaudhari, K and Kamat, D}, title = {The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID-Part I.}, journal = {Pediatric annals}, volume = {53}, number = {12}, pages = {e473-e477}, doi = {10.3928/19382359-20241003-03}, pmid = {39653343}, issn = {1938-2359}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Systemic Inflammatory Response Syndrome/diagnosis/physiopathology ; Child ; Infant ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mucocutaneous Lymph Node Syndrome/diagnosis ; }, abstract = {The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [Pediatr Ann. 2024;53(12):e473-e477.].}, } @article {pmid39652555, year = {2024}, author = {Morita, S and Tokumasu, K and Otsuka, Y and Honda, H and Nakano, Y and Sunada, N and Sakurada, Y and Matsuda, Y and Soejima, Y and Ueda, K and Otsuka, F}, title = {Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0315385}, pmid = {39652555}, issn = {1932-6203}, mesh = {Humans ; Female ; *Fatigue Syndrome, Chronic/epidemiology ; Male ; *COVID-19/epidemiology ; Japan/epidemiology ; Middle Aged ; Retrospective Studies ; Prevalence ; Adult ; SARS-CoV-2/isolation & purification ; Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023.

METHODS: Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria.

RESULTS: The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period.

CONCLUSION: The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words).}, } @article {pmid39652387, year = {2024}, author = {AbuRaed, AGT and Prikryl, EA and Carenini, G and Janjua, NZ}, title = {Long COVID Discourse in Canada, the United States, and Europe: Topic Modeling and Sentiment Analysis of Twitter Data.}, journal = {Journal of medical Internet research}, volume = {26}, number = {}, pages = {e59425}, pmid = {39652387}, issn = {1438-8871}, mesh = {*Social Media/statistics & numerical data ; *COVID-19/epidemiology/psychology ; Canada/epidemiology ; Humans ; United States/epidemiology ; Europe ; Pandemics ; Public Opinion ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Social media serves as a vast repository of data, offering insights into public perceptions and emotions surrounding significant societal issues. Amid the COVID-19 pandemic, long COVID (formally known as post-COVID-19 condition) has emerged as a chronic health condition, profoundly impacting numerous lives and livelihoods. Given the dynamic nature of long COVID and our evolving understanding of it, effectively capturing people's sentiments and perceptions through social media becomes increasingly crucial. By harnessing the wealth of data available on social platforms, we can better track the evolving narrative surrounding long COVID and the collective efforts to address this pressing issue.

OBJECTIVE: This study aimed to investigate people's perceptions and sentiments around long COVID in Canada, the United States, and Europe, by analyzing English-language tweets from these regions using advanced topic modeling and sentiment analysis techniques. Understanding regional differences in public discourse can inform tailored public health strategies.

METHODS: We analyzed long COVID-related tweets from 2021. Contextualized topic modeling was used to capture word meanings in context, providing coherent and semantically meaningful topics. Sentiment analysis was conducted in a zero-shot manner using Llama 2, a large language model, to classify tweets into positive, negative, or neutral sentiments. The results were interpreted in collaboration with public health experts, comparing the timelines of topics discussed across the 3 regions. This dual approach enabled a comprehensive understanding of the public discourse surrounding long COVID. We used metrics such as normalized pointwise mutual information for coherence and topic diversity for diversity to ensure robust topic modeling results.

RESULTS: Topic modeling identified five main topics: (1) long COVID in people including children in the context of vaccination, (2) duration and suffering associated with long COVID, (3) persistent symptoms of long COVID, (4) the need for research on long COVID treatment, and (5) measuring long COVID symptoms. Significant concern was noted across all regions about the duration and suffering associated with long COVID, along with consistent discussions on persistent symptoms and calls for more research and better treatments. In particular, the topic of persistent symptoms was highly prevalent, reflecting ongoing challenges faced by individuals with long COVID. Sentiment analysis showed a mix of positive and negative sentiments, fluctuating with significant events and news related to long COVID.

CONCLUSIONS: Our study combines natural language processing techniques, including contextualized topic modeling and sentiment analysis, along with domain expert input, to provide detailed insights into public health monitoring and intervention. These findings highlight the importance of tracking public discourse on long COVID to inform public health strategies, address misinformation, and provide support to affected individuals. The use of social media analysis in understanding public health issues is underscored, emphasizing the role of emerging technologies in enhancing public health responses.}, } @article {pmid39651728, year = {2024}, author = {Francavilla, F and Intranuovo, F and La Spada, G and Lacivita, E and Catto, M and Graps, EA and Altomare, CD}, title = {Inflammaging and Immunosenescence in the Post-COVID Era: Small Molecules, Big Challenges.}, journal = {ChemMedChem}, volume = {}, number = {}, pages = {e202400672}, doi = {10.1002/cmdc.202400672}, pmid = {39651728}, issn = {1860-7187}, abstract = {Aging naturally involves a decline in biological functions, often triggering a disequilibrium of physiological processes. A common outcome is the altered response exerted by the immune system to counteract infections, known as immunosenescence, which has been recognized as a primary cause, among others, of the so-called long-COVID syndrome. Moreover, the uncontrolled immunoreaction leads to a state of subacute, chronic inflammatory state known as inflammaging, responsible in turn for the chronicization of concomitant pathologies in a self-sustaining process. Anti-inflammatory and immunosuppressant drugs are the current choice for the therapy of inflammaging in post-COVID complications, with contrasting results. The increasing knowledge of the biochemical pathways of inflammaging led to disclose new small molecules-based therapies directed toward different biological targets involved in inflammation, immunological response, and oxidative stress. Herein, paying particular attention to recent clinical data and preclinical literature, we focus on the role of endocannabinoid system in inflammaging, and the promising therapeutic option represented by the CB2R agonists, the role of novel ligands of the formyl peptide receptor 2 and ultimately the potential of newly discovered monoamine oxidase (MAO) inhibitors with neuroprotective activity in the treatment of immunosenescence.}, } @article {pmid39651165, year = {2024}, author = {Wang, K and Nie, Y and Maguire, C and Syphurs, C and Sheen, H and Karoly, M and Lapp, L and Gygi, JP and Jayavelu, ND and Patel, RK and Hoch, A and , and Corry, D and Kheradmand, F and McComsey, GA and Fernandez-Sesma, A and Simon, V and Metcalf, JP and Higuita, NIA and Messer, WB and Davis, MM and Nadeau, KC and Kraft, M and Bime, C and Schaenman, J and Erle, D and Calfee, CS and Atkinson, MA and Brackenridge, SC and Hafler, DA and Shaw, A and Rahman, A and Hough, CL and Geng, LN and Ozonoff, A and Haddad, EK and Reed, EF and van Bakel, H and Kim-Schultz, S and Krammer, F and Wilson, M and Eckalbar, W and Bosinger, S and Langelier, CR and Sekaly, RP and Montgomery, RR and Maecker, HT and Krumholz, H and Melamed, E and Steen, H and Pulendran, B and Augustine, AD and Cairns, CB and Rouphael, N and Becker, PM and Fourati, S and Shannon, CP and Smolen, KK and Peters, B and Kleinstein, SH and Levy, O and Altman, MC and Iwasaki, A and Diray-Arce, J and Ehrlich, LIR and Guan, L}, title = {Unraveling SARS-CoV-2 Host-Response Heterogeneity through Longitudinal Molecular Subtyping.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.22.624784}, pmid = {39651165}, issn = {2692-8205}, abstract = {Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery. We confirmed that unresolved systemic inflammation and T-cell dysfunctions were hallmarks of increased severity and further distinguished patients with similar acute respiratory severity by their distinct immune profiles, which correlated with differences in demographic and clinical complications. Notably, one critical subtype (SubF) was uniquely characterized by early excessive inflammation, insufficient anticoagulation, and fatty acid dysregulation, alongside higher incidences of hematologic, cardiac, and renal complications, and an elevated risk of long COVID. Among the severe subtypes, significant differences in viral clearance and early antiviral responses were observed, with one subtype (SubC) showing strong early T-cell cytotoxicity but a poor humoral response, slower viral clearance, and greater risks of chronic organ dysfunction and long COVID. These findings provide crucial insights into the complex and context-dependent nature of COVID-19 immune responses, highlighting the importance of personalized therapeutic strategies to improve both acute and long-term outcomes.}, } @article {pmid39650838, year = {2024}, author = {An, H and Li, T and Zhang, X and Hu, H and Zhang, C and Wang, Y and Jin, S and Li, M}, title = {Persistent CD19[+] B cell lymphopenia in critically ill COVID-19 patients 50 days after symptom onset.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1488607}, pmid = {39650838}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/immunology ; *Lymphopenia/immunology ; *Critical Illness ; Male ; Female ; Middle Aged ; *B-Lymphocytes/immunology ; *SARS-CoV-2/immunology ; Aged ; *Antigens, CD19 ; Lymphocyte Count ; *Killer Cells, Natural/immunology ; Adult ; }, abstract = {INTRODUCTION: Long COVID (LC) poses a persistent challenge in clinical practice due to limited understanding of its etiology. LC is hypothesized to stem from aberrant immune responses in COVID-19. Vaccinations, which boost immune cells to restore function, could help ease LC symptoms.

METHODS: To exclude the impact of vaccination, we examined the immune cell profiles of recovering COVID-19 patients before vaccines were available. White blood cell differentials were monitored in ninety-twohealthy unvaccinated controls. Seventy-six unvaccinated COVID-19 patients were monitored upon admission and on the 50th day post-symptom onset (DPSO50). Peripheral lymphocyte subsets were analyzed using flow cytometry.

RESULTS: Mild cases showed no significant changes in lymphocyte counts or subsets from admission to DPSO50. By DPSO50, severe and critical cases showed almost complete recovery from lymphopenia, with critical cases having CD19+ B-cell counts approximately 45% lower than the mild group. Severe and critical cases exhibited reduced B-cell frequencies, with critical cases displaying around 48% higher natural killer (NK) cell counts. In mild cases, NK cell counts negatively correlated with B-cell counts (r=-0.528, p=0.02). Additionally, critical cases showed positive correlations between NK cell counts and CD4+ T-cell counts (r=0.83, p<0.01), and between NK cell counts and CD8+ T-cell counts (r=0.74, p<0.01). Severe cases demonstrated decreased counts of CD4+CD25+CD127lowFoxP3+ regulatory T-cells (Tregs), which positively correlated with B-cell counts (r=0.37, p<0.05).

DISCUSSION: Our findings indicate that aberrant immune cell profiles in COVID-19 patients change dynamically during recovery, depending on disease severity. This study suggests that convalescent patients from critical COVID-19 may experience long-lasting B-cell lymphopenia.}, } @article {pmid39644590, year = {2024}, author = {Rosolen, V and Beorchia, Y and Castriotta, L and Fanizza, C and Profili, F and Floridia, M and Giuliano, M and Pricci, F and Villa, M and Grisetti, T and Grassi, T and Tiple, D and Silenzi, A and Francesconi, P and Bisceglia, L and Barbone, F and Brusaferro, S and Onder, G}, title = {Insight into potential long COVID effects: Antidepressant use in post SARS-CoV-2 Infection scenarios. A multiregional nested case-control study.}, journal = {Psychiatry research}, volume = {344}, number = {}, pages = {116290}, doi = {10.1016/j.psychres.2024.116290}, pmid = {39644590}, issn = {1872-7123}, abstract = {This study aimed to investigate the impact of previous SARS-CoV-2 infection and the role of vaccination in the onset of neuropsychiatric conditions, evaluated through antidepressant prescriptions. This case-control study evaluated the risk of new antidepressant prescriptions in relation to previous exposure to SARS-CoV-2 infection and vaccination. It was conducted in three Italian Regions on adults who did not receive antidepressant prescriptions in the year preceding the study period. Individuals with newly prescribed antidepressants (cases) were matched by sex and age to non-users of antidepressants (controls). Pooled estimates of regional Odds Ratios (ORs) were obtained through a meta-analysis. Findings showed that individuals previously infected with SARS-CoV-2 had a higher risk of receiving a new prescription of antidepressants. Moreover, this association was stronger among subjects hospitalized due to infection, and SARS-CoV-2 vaccination may have acted as an effect modifier by reducing that risk. In fact, the pooled OR for receiving a new antidepressant prescription was higher for unvaccinated individuals than for those vaccinated. The results of this study confirm the role of SARS-CoV-2 infection as a risk factor for the onset of neuropsychiatric symptoms. Antidepressant treatment initiation was much more likely after severe COVID-19 infection but vaccination reduced such a risk.}, } @article {pmid39644382, year = {2024}, author = {Song, Z and Liu, C and Liu, Y and Bian, Z and Sun, Q and He, T and Su, R and Huang, S and Dai, N and Zhao, KL and Li, Y and Liang, K}, title = {Long-term dysregulation of plasma peptidome in mild and multiple COVID-19 recovered patients revealed by a novel efficient peptidomics workflow.}, journal = {Analytical and bioanalytical chemistry}, volume = {}, number = {}, pages = {}, pmid = {39644382}, issn = {1618-2650}, support = {202000205//Mountain Climbing Plan from the Foshan Hospital of TCM/ ; 2220001005517//Innovation Project of Science and Technology from Foshan City/ ; XDB38010200//Strategic Priority Research Program of Chinese Academy of Sciences/ ; 2022A1515110537//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2022YFF0713003//Key Research & Development Plan from the Chinese Ministry of Science and Technology/ ; KFJ-BRP-004//Biological Resources Programme of Chinese Academy of Sciences/ ; }, abstract = {After recovering from COVID-19, many patients experience "long COVID" symptoms. Existing research has predominantly focused on moderate to severe cases, with limited studies examining mild cases and recurrent infections. The circulating low-molecular-weight (LMW) peptidome, involving lipid metabolism, coagulation, and immune pathways, is crucial for understanding COVID-19's long-term effects. We developed a peptidomics workflow utilizing solid-phase extraction with highly wrinkled GO-Fe3O4 composite materials (HWGO-F) and nanoLC-MS/MS detection. By altering the pH, HWGO-F enhances plasma peptide adsorption and purification. Compared to traditional methods, our workflow offers improved detection depth and reproducibility for over 70% of peptide signals with CV < 20%. We investigated plasma peptide profiles in mild COVID-19 patients post-recovery from single or second infections. The findings indicate persistent abnormalities in initial COVID-19 infections' plasma peptide profiles, gradually diminishing over time. Secondary infections prolong recovery. Disrupted functions include lipid metabolism, coagulation and complement cascades, and infection-related pathways. Lipid metabolism may normalize within 3 months, while coagulation and immune abnormalities can last 3-6 months. After secondary infections, lipid metabolism irregularities may last at least 1 month, with extended coagulation and immune imbalances. These results provide a theoretical foundation for understanding the widespread occurrence of long COVID and guide recovery care for mild cases.}, } @article {pmid39642090, year = {2024}, author = {Rattanawijit, M and Samutpong, A and Apiwattanakul, N and Assawawiroonhakarn, S and Techasaensiri, C and Boonsathorn, S and Chaisavaneeyakorn, S}, title = {Rates, Risk Factors and Outcomes of Complications After COVID-19 in Children.}, journal = {The Pediatric infectious disease journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/INF.0000000000004649}, pmid = {39642090}, issn = {1532-0987}, support = {P-20-50966//the National Science and Technology Development Agency, Thailand, the Royal College of Pediatricians of Thailand and Pediatric Society of Thailand/ ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to various complications, including multisystem inflammatory syndrome in children (MIS-C) and post-COVID-19 conditions (long COVID). This study aimed to determine the rates, risk factors and outcomes of MIS-C and long COVID in children previously diagnosed with COVID-19.

METHODS: This study was a combined retrospective and prospective cohort study. Patients 0-18 years of age diagnosed with COVID-19 or another respiratory virus infection were enrolled between October 2021 and April 2022. Demographic and clinical data were reviewed. Information on persisting symptoms and their impacts were recorded at 1-3, 3-6 and 6-12 months after infection. Laboratory investigations and chest imaging examinations were performed during follow-up. MIS-C and long COVID were defined according to the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) definitions.

RESULTS: A total of 618 patients were enrolled, comprising 437 (70.7%) with COVID-19 and 181 (29.3%) with another respiratory virus infection. At 1-3 months, the rate of persisting symptoms was 16.5% in patients with COVID-19, compared with 1.1% in patients with another respiratory virus infection. The rate of MIS-C was 0.7%. The rate of long COVID according to the CDC and WHO definitions were 20.4% and 13.0%, respectively. Respiratory systems were most affected in long COVID. Age 5-18 years, anosmia during COVID-19, history of pneumonia and infection during the delta and omicron waves were associated with long COVID in children.

CONCLUSIONS: Long COVID after COVID-19 in children is uncommon. Children with anosmia and a history of pneumonia during COVID-19 require follow-up for long COVID.}, } @article {pmid39641021, year = {2024}, author = {Birtolo, LI and Di Pietro, G and Ciuffreda, A and Improta, R and Monosilio, S and Prosperi, S and Cimino, S and Galea, N and Severino, P and Galardo, G and Colaiacomo, MC and Pasculli, P and Petroianni, A and Palange, P and Mastroianni, CM and de Vito, L and Catalano, C and Pugliese, F and Ciardi, MR and Celli, P and Badagliacca, R and Fedele, F and Vizza, CD and Maestrini, V and Mancone, M and , }, title = {The impact of vaccination status on post-acute sequelae in hospitalized COVID-19 survivors using a multi-disciplinary approach: An observational single center study.}, journal = {Heliyon}, volume = {10}, number = {22}, pages = {e40409}, pmid = {39641021}, issn = {2405-8440}, abstract = {BACKGROUND: COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach.

METHODS: After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated "post-COVID-19 Outpatient Clinic". The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed.

RESULTS: Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results.

CONCLUSIONS: COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence.}, } @article {pmid39639960, year = {2024}, author = {Miller, CM and Borre, C and Green, A and Funaro, M and Oliveira, CR and Iwasaki, A}, title = {Postacute Sequelae of COVID-19 in Pediatric Patients Within the United States: A Scoping Review.}, journal = {American journal of medicine open}, volume = {12}, number = {}, pages = {100078}, pmid = {39639960}, issn = {2667-0364}, abstract = {A subset of children and adolescents experience recurrent or persistent symptoms following SARS-CoV-2 infection, known as postacute sequelae of COVID-19 (PASC), however, the clinical epidemiology within the United States (US) is not yet well understood. This scoping review aims to synthesize the clinical epidemiology of pediatric PASC in the US. A comprehensive literature search was conducted and databases were queried from inception until January 29, 2024. Studies including US children and adolescents <21 years old were considered. From 1028 studies identified, 29 met the inclusion criteria. Prevalence of PASC ranged from less than 1%-27%. Risk factors included older age, female sex, asthma, obesity, and severe initial infection. Common symptoms were dyspnea, fatigue, headaches, and chest pain. A multidisciplinary approach for diagnosis and management was common across studies. Most studies had a high risk of bias and were limited by a lack of standardized definitions and short follow-up duration. This review establishes a foundation for understanding pediatric PASC and highlights the critical need for continued research to optimize prevention and treatment strategies.}, } @article {pmid39639607, year = {2024}, author = {Adilović, M and Hromić-Jahjefendić, A and Mahmutović, L and Šutković, J and Rubio-Casillas, A and Redwan, EM and Uversky, VN}, title = {Intrinsic Factors Behind the Long-COVID: V. Immunometabolic Disorders.}, journal = {Journal of cellular biochemistry}, volume = {}, number = {}, pages = {e30683}, doi = {10.1002/jcb.30683}, pmid = {39639607}, issn = {1097-4644}, abstract = {The complex link between COVID-19 and immunometabolic diseases demonstrates the important interaction between metabolic dysfunction and immunological response during viral infections. Severe COVID-19, defined by a hyperinflammatory state, is greatly impacted by underlying chronic illnesses aggravating the cytokine storm caused by increased levels of Pro-inflammatory cytokines. Metabolic reprogramming, including increased glycolysis and altered mitochondrial function, promotes viral replication and stimulates inflammatory cytokine production, contributing to illness severity. Mitochondrial metabolism abnormalities, strongly linked to various systemic illnesses, worsen metabolic dysfunction during and after the pandemic, increasing cardiovascular consequences. Long COVID-19, defined by chronic inflammation and immune dysregulation, poses continuous problems, highlighting the need for comprehensive therapy solutions that address both immunological and metabolic aspects. Understanding these relationships shows promise for effectively managing COVID-19 and its long-term repercussions, which is the focus of this review paper.}, } @article {pmid39639510, year = {2024}, author = {Stave, GM}, title = {Long-Term Health Effects of COVID-19: Disability and Function Following SARS-CoV-2 Infection and A Long COVID Definition: A Chronic, Systemic Disease State with Profound Consequences.}, journal = {Journal of occupational and environmental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1097/JOM.0000000000003288}, pmid = {39639510}, issn = {1536-5948}, } @article {pmid39638836, year = {2024}, author = {Pham, A and Smith, J and Card, KG and Byers, KA and Khor, E}, title = {Exploring social determinants of health and their impacts on self-reported quality of life in long COVID-19 patients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {30410}, pmid = {39638836}, issn = {2045-2322}, support = {831887//Provincial Health Services Authority (Provincial Health Services Authority, British Columbia)/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Quality of Life ; Male ; Female ; Middle Aged ; *Social Determinants of Health ; Aged ; *Self Report ; Adult ; Retrospective Studies ; *SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; Depression/psychology ; British Columbia/epidemiology ; Anxiety/psychology ; Young Adult ; }, abstract = {This study explores the health-related quality of life (HRQoL) experienced by patients with Long COVD-19 using data from British Columbia's post-COVID-19 Recovery Clinics. A retrospective cohort of 3463 patients was analyzed to assess HRQoL through the EQ-5D-5L questionnaire which includes five dimensions (mobility, self-care, usual activities, physical health, and mental health) administered to patients; responses were analyzed using the Visual Analogue Score (VAS). Notably, 95% of participants reported HRQoL scores below 90, with 50% scoring under 60, indicating significant impacts on their well-being. The analysis revealed that HRQoL is significantly influenced by various social determinants of health (SDoH), including age, sex, employment status, and ethnicity, each showing distinct correlations with HRQoL dimensions and overall VAS scores. Specifically, older age was associated with decreased mobility and increased pain/discomfort but less anxiety and depression, highlighting varying impacts across the age spectrum. The study highlights the multifaceted impacts of Long COVID on the lives of patients and underscores the necessity of targeted strategies to improve HRQoL among diverse groups, considering specific SDoH. Such a comprehensive approach could lead to more equitable health outcomes and support the development of tailored public health policies aimed at the recovery and rehabilitation of Long COVID sufferers.}, } @article {pmid39635815, year = {2024}, author = {Tényi, D and Tényi, T and Janszky, J}, title = {[Long COVID - neurological or somatoform disease?].}, journal = {Ideggyogyaszati szemle}, volume = {77}, number = {11-12}, pages = {397-405}, doi = {10.18071/isz.77.0397}, pmid = {39635815}, issn = {0019-1442}, mesh = {Humans ; *COVID-19/complications/psychology ; *Somatoform Disorders/psychology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Nervous System Diseases/virology ; }, abstract = {BACKGROUND AND PURPOSE:

Post-COVID condition (also known as long COVID) is a syndrome characterized by persistent symptoms following a suspected or confirmed SARS-CoV-2 infection, lasting for at least two months and are not attributable to other conditions. The most common symptoms include fatigue, diffuse pain, post-exertional malaise and &ldquo;brain fog&rdquo; (impairment of memory and concentration). The pathomechanism of long COVID is the subject of ongoing, intensive research. Our purpose was to review the literature on the pathomechanism of long COVID.

.

METHODS:

We reviewed original and review articles in Hungarian and English on the pathomechanism of long COVID, published between January 2019 and June 2024, in the PubMed and Google Scholar databases.

.

RESULTS:

Potential underlying causes of the symptoms are outlined in three main theories. 1) The concept of &ldquo;long COVID as a distinct neurological disease&rdquo; suggests that direct viral neuroinvasion, apoptosis, and demyelination processes are responsible for the symptoms. 2) The theory of &ldquo;long COVID as a systemic disease with neurological symptoms&rdquo; is based on the virus induced, prolonged cytokine and chemokine release, as well as the reactivation of latent viral infections. 3) According to the concept of &ldquo;long COVID as a somatoform disorder&rdquo;, the disease results from abnormal activation of the proinflammatory cytokine network leading to central nervous system sensitization, a well-known psychoneuroimmunological mechanism. Our study highlighted significant overlaps between long COVID and conditions such as chronic fatigue syndrome/myalgic encephalomyelitis, a group of symptoms not defined as a distinct mental disorder in DSM-5, but commonly referred to as Gulf War syndrome, chronic Lyme disease and somatic symptom disorder.

.

CONCLUSION:

The pathomechanism of long COVID, which presents with a wide range of nonspecific symptoms, remains unknown, and no reproducible disease-specific biomarker has been identified to date. Clarifying the etiology of the disease is crucial for determining adequate and effective therapeutic methods.

.}, } @article {pmid39635598, year = {2024}, author = {Khan, MH and Becker, RC}, title = {Bridging the gap: strategies for recognizing and managing post-COVID conditions.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1395420}, pmid = {39635598}, issn = {2296-858X}, abstract = {Post-COVID conditions (PCC), pose significant challenges for healthcare providers, employers, community leaders, and patients because of their wide-ranging, fluctuating, or persisting symptoms without well-established diagnostic tests to secure a diagnosis. Estimates suggest that up to 20-30% of adults recovering from COVID-19 develop PCC, potentially affecting millions or tens of millions of people in the United States alone. The ongoing endemic coupled with the prevalence of PCC underscores an urgent need for awareness and an understanding of potentially associated conditions, long-term management strategies, and cost-effective screening approaches for cardiovascular health. Individuals experiencing PCC present with a wide array of symptoms. Prevalence of chronic conditions such as post-infectious pulmonary fibrosis, cardiomyopathy, and accelerated coronary artery, cerebrovascular, and peripheral vascular disease further emphasizes the need for community-wide policies and practices. Screening for PCC is recommended, particularly among high-risk individuals, including those with comorbid conditions and exposure to specific SARS-CoV-2 variants, to facilitate early diagnosis, counseling, targeted interventions, and improved quality of life. The aim of this review is to highlight the urgent need for awareness, understanding and management of PCC, focusing on development of screening strategies and targeted interventions to help facilitate early diagnosis and enhance the quality of life for affected individuals. In our view early detection and management of PCC not only improves the quality of life but also improves psychosocial health. Patient-centered approaches, standardized screening tools, and initiatives aimed at enhancing understanding and treatment options, such as the RECOVER and N3C programs, are essential for effective management of PCC.}, } @article {pmid39633013, year = {2024}, author = {Stephenson, T and Pinto Pereira, SM and Nugawela, MD and Dalrymple, E and Harnden, A and Whittaker, E and Heyman, I and Ford, T and Segal, T and Chalder, T and Ladhani, SN and McOwat, K and Simmons, R and Xu, L and Fox-Smith, L and , and Shafran, R}, title = {A 24-month National Cohort Study examining long-term effects of COVID-19 in children and young people.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {255}, pmid = {39633013}, issn = {2730-664X}, support = {COVLT0022//DH | National Institute for Health Research (NIHR)/ ; MR/P020372/1//RCUK | Medical Research Council (MRC)/ ; MR/Y009398/1//RCUK | Medical Research Council (MRC)/ ; }, abstract = {BACKGROUND: Some children and young people (CYP) infected with SARS-COV-2 experience impairing symptoms post-infection, known as post-COVID-19 condition (PCC). Using data from the National Long COVID in Children and Young People (CloCk) study, we report symptoms and their impact up to 24-months post-infection.

METHODS: CloCk is a cohort of CYP in England aged 11-to-17-years when they had a SARS-CoV-2 PCR-test (between September 2020 and March 2021). Of 31,012 eligible CYP 24-months post-PCR test, 12,632 participated (response = 40.7%). CYP were grouped by infection status: 'initial test-negatives; no subsequent positive-test' (NN); 'initial test-negatives; subsequent positive-test' (NP); 'initial test-positives; no reported re-infection' (PN); and 'initial test-positives; reported re-infection' (PP). The Delphi research definition of PCC in CYP was operationalised; symptom severity/impact and validated scales (e.g., Chalder Fatigue Scale) were recorded. We examine symptom profiles 24-month post-index-test by infection status.

RESULTS: 7.2% of CYP consistently fulfil the PCC definition at 3-, 6-, 12- and 24-months. These CYPs have a median of 5-to-6 symptoms at each time-point. Between 20% and 25% of all infection status groups report 3+ symptoms 24-months post-testing; 10-25% experience 5+ symptoms. The reinfected group has more symptoms than the other positive groups; the NN group has the lowest symptom burden (p < 0.001). PCC is more common in older CYPs and in the most deprived. Symptom severity/impact is higher in those fulfilling the PCC definition.

CONCLUSIONS: The discrepancy in the proportion of CYP fulfilling the Delphi PCC definition at 24-months and those consistently fulfilling the definition across time, highlights the importance of longitudinal studies and the need to consider clinical impairment and range of symptoms.}, } @article {pmid39631854, year = {2024}, author = {Mahase, E}, title = {Long covid: 70% of 11-17 year olds recover within two years, study reports.}, journal = {BMJ (Clinical research ed.)}, volume = {387}, number = {}, pages = {q2713}, doi = {10.1136/bmj.q2713}, pmid = {39631854}, issn = {1756-1833}, } @article {pmid39631631, year = {2024}, author = {Tang, CH and Yang, YF and Fung Poon, KC and Man Wong, HY and Hei Lai, KK and Li, CK and Yan Chan, JW and Wing, YK and Dou, Q and Yung Tham, CC and Pang, CP and Lung Chong, KK}, title = {Virtual Reality-based Infrared Pupillometry (VIP) for long COVID.}, journal = {Ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ophtha.2024.11.026}, pmid = {39631631}, issn = {1549-4713}, abstract = {OBJECTIVE: To evaluate the use of virtual reality-based infrared pupillometry (VIP) to detect individuals suffering long COVID.

DESIGN: Prospective, case-control cross-sectional study.

PARTICIPANTS: Participants aged 20-60 were recruited from a community eye screening programme.

METHODS: Pupillary Light Responses (PLR) were recorded in response to 3 intensities of light stimuli (L6, L7 and L8) using a virtual reality head-mount display (VR-HMD). 9 PLR waveform features for each stimulus, were extracted by 2 masked observers and statistically analyzed. We also use various methods on the whole PLR waveform including trained, validated and tested (6:3:1) by machine learning models including Multi-layer Perceptron, Support Vector Machine, K-nearest Neighbors, Logistic Regression, Decision Tree, Random Forest and Long Short-Term Memory (LSTM) models for two and three-class classification into long-COVID (LCVD), post-COVID (PCVD) or control.

MAIN OUTCOME MEASURES: Accuracies/AUC of individual or combination of PLR features and ML models using PLR features or whole pupillometric waveform.

RESULTS: PLR from a total of 185 subjects including 112 LCVD, 44 PCVD and 29 age/sex-matched controls were analysed. Models examined the independent effects of age and sex. Constriction Time(CT) after the brightest stimulus(L8) is significantly associated with LCVD status(two-way ANOVA, false discovery rate(FDR)<0.001; multinominal logistic regression, FDR<0.05). The overall accuracy/AUC of CT-L8 alone in differentiating LCVD from control or from PCVD were 0.7808/0.8711 and 0.8654/0.8140 respectively. Using cross-validated backward stepwise variable selection, CT-L8, CT-L6, Constriction Velocity(CV)-L6 were most useful to detect LCVD while CV-L8 for PCVD from other groups. The accuracy/AUC of selected features were 0.8000/0.9000 (control versus LCVD) and 0.9062/0.9710 (PCVD versus LCVD), better than when all 27 pupillometric features were combined. An LSTM model analyzing whole pupillometric waveform achieved the highest accuracy/AUC at 0.9375/1.000 in differentiating LCVD from PCVD and a slightly lower accuracy of 0.7838 for three-class classification (LCVD-PCVD-control).

CONCLUSIONS: We reported, for the first time, specific pupillometric signatures in differentiating LCVD from PCVD or control subjects using a VR-HMD. Combining statistical methods to identify specific pupillometric features and ML algorithms to analyse the performance further enhance the performance of VIP as a non-intrusive, low-cost, portable and objective method to detect and monitor long COVID.}, } @article {pmid39631173, year = {2024}, author = {Shaver, JLF and Woods, NF and Von Ah, D and Alexander, IM}, title = {Persistent post COVID-19: Implications for women's health research and policy from members of the Women's Health Expert Panel of the American Academy of Nursing.}, journal = {Nursing outlook}, volume = {73}, number = {1}, pages = {102341}, doi = {10.1016/j.outlook.2024.102341}, pmid = {39631173}, issn = {1528-3968}, abstract = {BACKGROUND: Despite that globally the percent of women and men who tested positive for COVID-19 appears equal and that men with COVID-19 were 60% more likely than women to be severely ill and to die from complications (Rozenberg et al., 2020), studies of sex differences show that women compared with men are more likely to manifest persistent post-COVID-19 syndrome (PPCS).

PURPOSE: In this paper, we address some of the extant evidence for impact of the PPCS on women's health and well-being to underpin our suggestions for research and policy considerations.

METHODS: We assessed key papers in the extant literature to formulate views on needed health-related research and policies.

DISCUSSION: We discuss how key PPCS manifestations vary by sex, resemble sequelae uncovered for other chronically fatiguing or serious postinfectious trauma conditions, influence women's reproductive health (e.g., menstrual cycle, fertility, pregnancy, and menopause transition), impair women's social function and economic productivity, and challenge what is required for influential treatment and prevention.

CONCLUSION: To inform effective diagnosis, management and prevention of the significantly prevalent and debilitating PPCS, high on research and policy agendas should be uncovering multidimensional evidence of the impact on women, especially on their overall and reproductive health, well-being, social function and economic productivity.}, } @article {pmid39628664, year = {2024}, author = {An, H and Li, T and Yang, L and Zhang, X and Hu, H and Zhang, C and Wang, Y and Jin, S and Li, M}, title = {Unveiling the hidden link: elevated platelets and T cell subsets in 5% of moderate COVID-19 patients 48 days post-onset.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1498491}, pmid = {39628664}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/immunology/blood/complications ; Male ; Female ; Middle Aged ; *Blood Platelets/immunology ; Longitudinal Studies ; *T-Lymphocyte Subsets/immunology ; *SARS-CoV-2/immunology ; Platelet Count ; Adult ; Aged ; CD8-Positive T-Lymphocytes/immunology ; }, abstract = {INTRODUCTION: Platelets are hyperactived during acute COVID-19, promoting clotting and modulating immune-cell responses. Immune thrombocytopenia in adults can manifest as an uncommon complication resulting from various viral infections or as a rare adverse event associated with vaccination. However, their role in convalescent COVID-19 patients remains underexplored. This study examines platelet dynamics early in the pandemic, 48 days post-symptom onset, in unvaccinated patients.

METHODS: This longitudinal study included 298 unvaccinated COVID-19 patients (17 mild, 281 moderate) from multiple centers. Clinical evaluations and peripheral lymphocyte subset analyses via flow cytometry were conducted upon admission and on day 48 post-symptom onset (DPSO 48).

RESULTS: At DPSO 48, 5.3% of moderate COVID-19 patients exhibited high platelet counts (>300×10[9]/L), associated with elevated total T-cells (26.4%), CD4 T-cells (24.4%), CD8 T-cells (36.9%), and Tregs (33.9%) compared to patients with normal platelet counts. However, the CD4/CD8 T-cell ratio and T-cell subset frequencies remained unaffected, indicating ongoing T-cell homeostasis restoration. Additionally, a significant positive correlation (r=0.636, p=0.03) was found between platelet counts and B cells in patients with elevated platelet counts.

DISCUSSION: Platelets may play a pivotal role in immune regulation during the recovery phase of COVID-19. Targeting platelets and their secreted mediators could improve immune balance in patients with immune disorders, highlighting a potential therapeutic approach for enhancing recovery in post-COVID-19 patients.}, } @article {pmid39628552, year = {2024}, author = {Dehghan, M and Mirzohreh, ST and Kaviani, R and Yousefi, S and Pourmehran, Y}, title = {A deeper look at long-term effects of COVID-19 on myocardial function in survivors with no prior heart diseases: a GRADE approach systematic review and meta-analysis.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1458389}, pmid = {39628552}, issn = {2297-055X}, abstract = {OBJECTIVES: The COVID-19 pandemic has challenged global health systems since December 2019, with the novel virus SARS-CoV-2 causing multi-systemic disease, including heart complications. While acute cardiac effects are well-known, long-term implications are understudied. This review hopes to fill a gap in the literature and provide valuable insights into the long-term cardiac consequences of the virus, which can inform future public health policies and clinical practices.

METHODS: This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. A meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked.

RESULTS: Sixty-six studies were included in this review. Thirty-two of them enrolled in meta-analysis and the rest in qualitative synthesis. Most outcomes showed a moderate certainty of evidence according to the GRADE framework. Post-COVID individuals with no prior heart diseases showed significant changes in left ventricular (LV) and right ventricular (RV) echocardiographic indices compared to controls. These significant findings were seen in both post-acute and long-COVID survivors regardless of the severity of initial infection.

CONCLUSION: This review implies that individuals recovering from post-acute and long-term effects of COVID-19 may experience changes in myocardial function as a result of the novel coronavirus. These changes, along with cardiac symptoms, have been observed in patients without prior heart diseases or comorbidities.

PROSPERO, identifier (CRD42024481337).}, } @article {pmid39628270, year = {2025}, author = {Duong-Quy, S and Nguyen Hai, C and Huynh-Anh, T and Nguyen-Nhu, V}, title = {Tackling pulmonary fibrosis risks in post-COVID-19: cutting-edge treatments.}, journal = {Expert opinion on pharmacotherapy}, volume = {26}, number = {1}, pages = {75-84}, doi = {10.1080/14656566.2024.2438322}, pmid = {39628270}, issn = {1744-7666}, mesh = {Humans ; *Pulmonary Fibrosis/etiology/drug therapy ; *COVID-19/complications ; Antifibrotic Agents/therapeutic use ; Tomography, X-Ray Computed ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) post-COVID-19 has been identified as an important complication of Long-COVID, especially in patients with severe respiratory symptoms. High-resolution computed tomography (HRCT) is the main tool for detecting fibrotic lesions in patients with PF post-COVID-19.

AREAS COVERED: We conducted a systematic review with the following objectives: (1) to summarize the incidence and disease burden of post‑COVID‑19 pulmonary fibrosis, (2) to provide information on available therapies and drugs for its management, (3) to comprehensively evaluate the initial treatment efficacy of these drugs, and (4) to identify the limitations and challenges associated with current treatment approaches.

EXPERT OPINION: Cutting-edge treatments for PF post-COVID-19 are focused on the complex and multifactorial nature of the disease progreession during Long COVID, which involves chronic inflammation, fibroblast activation, and excessive extracellular matrix deposition leading to stiffening and fibrosis of lung tissue. While traditional antifibrotic drugs with nintedanid and pirfenidone are being used, novel therapies with anti-interleukines, mesenchymal stem cells, and Rho-kinase inhibitors promise the new treatment approaches for patients with PF post-COVID-19. Further research and clinical trials are needed to determine the most effective strategies for managing this complex condition, with the goal of improving patient outcomes and quality of life.}, } @article {pmid39625700, year = {2024}, author = {Blondeau, JM}, title = {Long COVID: a consequence of chronic post-infectious inflammation!.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {12}, pages = {939-945}, doi = {10.1080/17476348.2024.2438104}, pmid = {39625700}, issn = {1747-6356}, mesh = {Humans ; *COVID-19/immunology/complications ; *Inflammation/immunology/virology ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/immunology ; }, abstract = {INTRODUCTION: Long COVID defines persistence of symptoms in patients that recovered from acute COVID-19 infections. This manuscript is a brief update on current thinking on long COVID and potential causes and consequences.

AREAS COVERED: The extent of long COVID varies between patients with some 200 symptoms described and of different severities. Persistent inflammatory or persistent viral infections or both may be the cause of long COVID but sorting this out will take years.

EXPERT OPINION: Long COVID is an unfortunate consequence of COVID-19 infection and it remains uncertain why some people are afflicted and others not and as with other infectious diseases, it may be both a function of the virus strain, the host or both. Direct organ damage during acute infection versus inflammatory mediated damage over time are important questions to address. The disease outcome and chronic sequelae are likely related to the strains of infectious agent and/or host immunity and genetic predisposition.}, } @article {pmid39624957, year = {2024}, author = {Haihong, L and Nannan, X and Xiangzhu, M and Gang, W}, title = {A clinical case study of seven patients of autonomic dysfunction in post COVID-19 conditions with fever as the main clinical symptom: a case series.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2402943}, pmid = {39624957}, issn = {1365-2060}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Autonomic Nervous System Diseases/physiopathology/diagnosis ; *COVID-19/complications/physiopathology ; Fever/physiopathology/virology/etiology ; Fever of Unknown Origin/etiology/physiopathology/virology ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: Many publications have reported that acute COVID-19 infection can cause autonomic dysfunction. In this series, we described seven patients who had recurrent fever after acute COVID-19 infection, and the possible pathophysiological basis is autonomic dysfunction.

PATIENTS: This was a retrospective study conducted at the Qilu Hospital of Shandong University from January 2023 to March 2023. Patients who were hospitalized in the Department of Infectious Diseases with a diagnosis of fever of unknown origin.

RESULTS: Between January and March 2023, a total of seven patients with autonomic dysfunction in post-COVID condition, who had recurrent fever accompanied by electrolyte imbalances and other manifestations of autonomic dysfunction. The median age of these patients was relatively high, and they were mostly indoor workers with comorbidities such as diabetes and chronic hypertension. Physical cooling and correction of electrolyte imbalances with medication were effective treatments.

CONCLUSIONS: The COVID-19 infection can lead to autonomic dysfunction, which manifests not only as tachycardia and blood pressure abnormalities, but may also be the pathophysiological mechanism underlying recurrent fever in post-COVID cases.}, } @article {pmid39624781, year = {2025}, author = {Georgakopoulou, VE and Taskou, C and Spandidos, DA and Sarantaki, A}, title = {Long COVID‑19 and pregnancy: A systematic review.}, journal = {Biomedical reports}, volume = {22}, number = {1}, pages = {15}, pmid = {39624781}, issn = {2049-9442}, abstract = {The impact of post-acute sequelae of SARS-CoV-2 infection, or Long coronavirus disease 2019 (COVID-19), on pregnant women remains a growing concern. The present systematic review synthesizes current evidence on the prevalence, risk factors and clinical outcomes of Long COVID-19 in pregnant women to improve understanding of its burden and implications for maternal health. A systematic search was conducted in PubMed, Scopus and Google Scholar for studies published between January 2020 and October 2024. Eligible studies included pregnant or postpartum women diagnosed with COVID-19 and followed for at least four weeks post-infection. Data extraction and quality assessment were performed using standardized tools, and the findings were narratively synthesized due to heterogeneity in study designs and outcome measures. A total of 13 studies encompassing 13,729 participants were included. The prevalence of Long COVID-19 varied widely, ranging from 9.3-93%. The most reported symptoms included fatigue, cognitive dysfunction, respiratory symptoms and psychological disturbances, with fatigue being the most prevalent. Severe acute COVID-19, obesity, pre-existing mental health conditions, and non-vaccination were identified as key risk factors for developing Long COVID-19. Several studies reported that women with Long COVID-19 were at a higher risk for adverse maternal and neonatal outcomes, such as preterm birth and increased need for neonatal intensive care. The severity of acute infection and the presence of comorbidities significantly influenced the risk and severity of Long COVID-19. Long COVID-19 is a prevalent condition among pregnant women, with significant variability in reported prevalence rates. It is associated with a range of symptoms that can impact maternal health and pregnancy outcomes. The findings highlight the need for targeted follow-up and management strategies in this population. Standardized definitions and longitudinal studies are essential to further elucidate the long-term impact of COVID-19 during pregnancy.}, } @article {pmid39624484, year = {2024}, author = {LaCourse, C}, title = {Utilizing HCoV-OC43 to better understand the neurological impact of COVID-19.}, journal = {Brain, behavior, & immunity - health}, volume = {42}, number = {}, pages = {100905}, pmid = {39624484}, issn = {2666-3546}, abstract = {As the COVID-19 pandemic enters its fifth year, research tools to study the SARS-CoV-2 (CoV-2) virus are critical, and many researchers have turned to another beta coronavirus: HCoV-OC43 (OC43). OC43 is a ubiquitous pathogen that now causes a common cold, but its emergence in 1890 closely coincided with and likely produced the catastrophic Russian Flu pandemic. Beyond their historical parallels, OC43 and CoV-2 share similar genetics and disease sequelae. Both viruses induce respiratory symptoms. Additionally, OC43 infection can result in acute neurological dysfunction in children, and exposure to OC43 has been linked to long-term neurological disorders in adults. Similarly, CoV-2 can produce acute neuropathology and the phenomenon of prolonged symptoms known as Long-COVID that typically impacts the brain. Mouse models have been developed to study the pathogenesis of both OC43 and CoV-2, thereby facilitating research on the neurological sequelae associated with either infection. These models have been further utilized to test therapeutic interventions against both viruses, as researchers seek to establish the potential for using OC43 as a proxy for CoV-2. Further, because mouse models of the two betacoronaviruses exhibit neurological sequelae, using OC43 likely could provide insight into the impact of COVID-19 on the brain. OC43 requires a lower biosafety level than CoV-2, which makes it accessible to more researchers resulting in expeditious scientific progress in the ongoing COVID-19 pandemic.}, } @article {pmid39624388, year = {2024}, author = {Oo, A and Chu, JJH}, title = {Precision disease management: prognostic biomarker for chronic lung damage in long COVID.}, journal = {ERJ open research}, volume = {10}, number = {6}, pages = {}, pmid = {39624388}, issn = {2312-0541}, abstract = {Early detection of potential severe disease progression facilitates implementation of relevant precise disease management strategies. MMP-7 is a reliable prognostic biomarker for long COVID persistent lung damage that should be considered for clinical use. https://bit.ly/3Ccxozg.}, } @article {pmid39619281, year = {2024}, author = {Sun, L and Li, N and Li, H and Zhang, Q and Bao, S and Li, X}, title = {A Potential Therapeutic Effect of Suxiao Jiuxin Pills in Treating Postacute Sequelae of COVID-19: Case Report.}, journal = {Case reports in infectious diseases}, volume = {2024}, number = {}, pages = {4713552}, pmid = {39619281}, issn = {2090-6625}, abstract = {Postacute Sequelae of COVID-19 Cardiovascular Syndrome (PASC-CVS) refers to a broad spectrum of cardiovascular symptoms that manifest four weeks or more after infection with COVID-19, which cannot be diagnosed as cardiovascular disease through standard examinations. Common symptoms include exercise intolerance and tachycardia, alongside persistent issues such as chest pain, chest tightness, and difficulty breathing. PASC-CVS significantly affects patients' quality of life; however, effective treatments for this condition are currently lacking. In this report, we present two cases of PASC-CVS patients who experienced well-controlled cardiovascular symptoms following treatment with Suxiao Jiuxin Pills. Our findings may offer a novel approach to the clinical management of PASC-CVS.}, } @article {pmid39618261, year = {2024}, author = {Datta, BK and Fazlul, I and Khan, MM}, title = {Long COVID and financial hardship: A disaggregated analysis at income and education levels.}, journal = {Health services research}, volume = {}, number = {}, pages = {}, doi = {10.1111/1475-6773.14413}, pmid = {39618261}, issn = {1475-6773}, support = {//No external funding was received for this project./ ; }, abstract = {OBJECTIVES: To examine how long COVID is associated with financial hardship (food insecurity, inability to pay bills, or threat of losing service) across income and education levels, and to assess the role of employment loss or reduced work hours in this hardship.

DATA SOURCE AND STUDY SETTING: We used nationally representative data on 271,076 adults from the 2022 Behavioral Risk Factor Surveillance System (BRFSS).

STUDY DESIGN: We used multivariable binomial logistic regression models to estimate the average marginal effect of long COVID on financial hardships across multiple income and education groups.

PRINCIPAL FINDINGS: In general, we found a significant positive association between long COVID and the three measures of financial hardships across income and education groups (1-11 percentage points increase, 95% CI 0.00-0.02 and 0.07-0.14, respectively). Mediation analysis showed that lost or reduced hours of employment accounted for a significant portion (6%-20%) of the changes in financial distress.

CONCLUSIONS: Long COVID has affected the economic wellbeing of people from all socioeconomic statuses, although at a higher rate for lower income groups. Policy attention is needed to address its economic impacts across income and education levels.}, } @article {pmid39615603, year = {2024}, author = {Shahbaz, S and Rezaeifar, M and Syed, H and Redmond, D and Terveart, JWC and Osman, M and Elahi, S}, title = {Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.11.032}, pmid = {39615603}, issn = {1090-2139}, abstract = {A substantial portion of patients infected with SARS-CoV-2 experience prolonged complications, known as Long COVID (LC). A subset of these patients exhibits the most debilitating symptoms, similar to those defined in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We performed bulk RNA sequencing (RNAseq) on the whole blood of LC with ME/CFS, at least 12 months post-onset of the acute disease, and compared them with controls. We found that LC patients had a distinct transcriptional profile compared to controls. Key findings include the upregulation of genes involved in immune dysregulation and neuronal development, such as Fezf2, BRINP2, HOXC12, MEIS2, ZFHX3, and RELN. These genes are linked to neuroinflammatory responses, cognitive impairments, and hematopoietic disturbances, suggesting ongoing neurological and immune disturbances in LC patients. RELN, encoding the Reelin protein, was notably elevated in LC patients, potentially serving as a biomarker for LC pathogenesis due to its role in inflammation and neuronal function. Immune cell analysis showed altered profiles in LC patients, with increased activated memory CD4 + T cells and neutrophils, and decreased regulatory T cells and NK cells, reflecting immune dysregulation. Changes in cytokine and chemokine expression further underscore the chronic inflammatory state in LC patients. Notably, a unique upregulation of olfactory receptors (ORs) suggest alternative roles for ORs in non-olfactory tissues. Pathway analysis revealed upregulation in ribosomal RNA processing, amino acid metabolism, protein synthesis, cell proliferation, DNA repair, and mitochondrial pathways, indicating heightened metabolic and immune demands. Conversely, downregulated pathways, such as VEGF signaling and TP53 activity, point to impaired tissue repair and cellular stress responses. Overall, our study underscores the complex interplay between immune and neuronal dysfunction in LC patients, providing insights into potential diagnostic biomarkers and therapeutic targets. Future research is needed to fully understand the roles and interactions of these genes in LC pathophysiology.}, } @article {pmid39615487, year = {2024}, author = {Rong, Z and Mai, H and Ebert, G and Kapoor, S and Puelles, VG and Czogalla, J and Hu, S and Su, J and Prtvar, D and Singh, I and Schädler, J and Delbridge, C and Steinke, H and Frenzel, H and Schmidt, K and Braun, C and Bruch, G and Ruf, V and Ali, M and Sühs, KW and Nemati, M and Hopfner, F and Ulukaya, S and Jeridi, D and Mistretta, D and Caliskan, ÖS and Wettengel, JM and Cherif, F and Kolabas, ZI and Molbay, M and Horvath, I and Zhao, S and Krahmer, N and Yildirim, AÖ and Ussar, S and Herms, J and Huber, TB and Tahirovic, S and Schwarzmaier, SM and Plesnila, N and Höglinger, G and Ondruschka, B and Bechmann, I and Protzer, U and Elsner, M and Bhatia, HS and Hellal, F and Ertürk, A}, title = {Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.}, journal = {Cell host & microbe}, volume = {32}, number = {12}, pages = {2112-2130.e10}, doi = {10.1016/j.chom.2024.11.007}, pmid = {39615487}, issn = {1934-6069}, mesh = {*COVID-19/metabolism/virology ; Animals ; *Spike Glycoprotein, Coronavirus/metabolism ; Humans ; Mice ; *SARS-CoV-2 ; *Brain/virology/metabolism ; *Disease Models, Animal ; *Meninges/virology/metabolism ; *Skull/virology ; Male ; Female ; Proteomics ; Stroke/metabolism/virology ; Neuroinflammatory Diseases/metabolism/virology ; Mice, Inbred C57BL ; Brain Injuries, Traumatic/metabolism/virology ; }, abstract = {SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.}, } @article {pmid39611942, year = {2024}, author = {Berg, OK and Aagård, N and Helgerud, J and Brobakken, MF and Hoff, J and Wang, E}, title = {Maximal oxygen uptake, pulmonary function and walking economy are not impaired in patients diagnosed with long COVID.}, journal = {European journal of applied physiology}, volume = {}, number = {}, pages = {}, pmid = {39611942}, issn = {1439-6327}, abstract = {INTRODUCTION: SARS-CoV-2 may result in the development of new symptoms, known as long COVID, a few months after the original infection.

PURPOSE: It is elusive to what extent physical capacity in patients diagnosed with long COVID is impacted.

METHODS: We compared maximal oxygen uptake (V̇O2max), one of the single most important factors for cardiovascular health and mortality, expired lung volumes and air flow, oxygen cost of walking and 6-min-walking-test (6MWT), in 20 patients diagnosed with long COVID (11 males and 9 females; 44 ± 16 years (SD); 26.7 ± 3.8BMI, duration of acute phase 1.7 ± 1.2 weeks, tested 4 ± 3 months after long COVID diagnosis) with 20 healthy age and sex matched controls (11 males and 9 females; 44 ± 16 years; 25.9 ± 4.0BMI).

RESULTS: Long COVID patients had a V̇O2max of 41.4 ± 16.2 mL∙kg[-1]∙min[-1](men) and 38.2 ± 7.5 (women) and this was not different from controls. Similarly, mean spirometry measures in the patient group (VC; FVC; FEV1; FEV1/FVC) were also not different (85-106%) from predicted healthy values. Finally, inclined treadmill (5%, 4 km∙h[-1]) walking economy was not different between the groups (long COVID: 15.2 ± 1.1 mL∙kg[-1]∙min[-1]; controls: 15.2 ± 1.2 mL∙kg[-1]∙min[-1]), while the 6MWT revealed a difference (long COVID: 606 ± 118 m; controls: 685 ± 85 m; p = 0.036).

CONCLUSION: V̇O2max, oxygen cost of walking, and spirometry measurements did not appear to be impaired in patients diagnosed with long COVID with a prior mild to moderate SARS-CoV-2 infection. The typical outcomes in these essential factors for health and longevity implies that while long COVID can present with a range of symptoms, caution should be made when attributing these symptoms directly to compromised pulmonary function or V̇O2max.}, } @article {pmid39611465, year = {2024}, author = {Igarashi, Y and Tateishi, S and Harada, A and Hino, A and Tsuji, M and Ando, H and Matsuda, S and Fujino, Y and Mori, K}, title = {Association of workplace stressors prior to infection and the development of Long COVID among workers during the COVID-19 pandemic: a cohort study in Japan.}, journal = {Journal of occupational health}, volume = {66}, number = {1}, pages = {}, pmid = {39611465}, issn = {1348-9585}, support = {//University of Occupational and Environmental Health/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Japan/epidemiology ; Male ; Female ; Adult ; *Occupational Stress/epidemiology/psychology ; Prospective Studies ; Middle Aged ; *Workplace/psychology ; Surveys and Questionnaires ; SARS-CoV-2 ; Risk Factors ; Social Support ; Cohort Studies ; }, abstract = {OBJECTIVES: Long COVID is a global health concern. Although various risk factors are known, the link between workplace factors and Long COVID is underexplored. We conducted a cohort study to examine the impact of preinfection workplace stressors on Long COVID among Japanese workers, with the aim of improving understanding of its disease process and inform workplace management.

METHODS: This prospective cohort study used online survey data collected in December 2020 and December 2022 from 1539 participants with no initial infection history but later reported COVID-19. Workplace stressors were assessed at baseline using the Job Content Questionnaire, which measured job demands, job control, and social support. At the follow-up survey, COVID-19 infection was determined by self-reported positive SARS-CoV-2 test by polymerase chain reaction or antigen, and development of Long COVID was defined as symptoms persisting for over 2 months. Univariate and multivariate logistic regression analyses estimated odds ratios (ORs) for the association between workplace stressors and the development of Long COVID.

RESULTS: Of the participants, 248 reported Long COVID. Univariate analysis showed that both high job demands (OR: 1.55; 95% CI, 1.09-2.20) and poor job control (OR: 1.50; 95% CI, 1.04-2.18) increased the odds. Poor supervisor support (OR: 1.73; 95% CI, 1.16-2.58) and co-worker support (OR: 1.59; 95% CI, 1.13-2.23) were also significant. On multivariate analysis, job demands remained significantly associated with Long COVID.

CONCLUSIONS: Our findings indicate that preinfection workplace stressors may contribute to Long COVID development in workers. Managing workplace stressors effectively could be a preventive measure.}, } @article {pmid39611127, year = {2024}, author = {Chiang, YF and Jiang, RS}, title = {Effect of oral zinc and steroids on long COVID hyposmia and hypogeusia.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241301894}, pmid = {39611127}, issn = {2050-3121}, abstract = {OBJECTIVE: We studied the prognosis of olfactory and gustatory dysfunctions in patients with long COVID (Coronavirus Disease 2019) after treatment with oral zinc and steroids.

METHODS: We measured olfactory and gustatory functions of long COVID patients at their first visits, and after 2-4 months of treatment with oral zinc and steroids using the traditional Chinese version of the University of Pennsylvania Smell Identification Test and the Waterless Empirical Taste Test. We also assessed by phone the recovery of olfactory and gustatory functions at a mean of about 10 months of follow-up.

RESULTS: Among our 71 long COVID patients, 34 complained of loss of smell and taste. Their objective test results showed 88.2% hyposmic, 23.5% hypogeusic at the first visit. After treatment, 77.8% of the patients were hyposmic, and 16.7% were hypogeusic. After a mean follow-up of 10.35 months, 91.2% of the patients reported improvement in their olfactory function. Among the 36 patients who had complained only of smell loss, the objective test results showed 75% hyposmic at their first visit. After treatment, 71.4% of the patients were hyposmic. After a mean of 10.42 months of follow-up, 77.8% of the patients reported improvement in their olfactory function. Only one patient complained of taste loss.

CONCLUSIONS: We found that olfactory dysfunction in most long COVID patients persisted for more than 10 months.}, } @article {pmid39610330, year = {2024}, author = {Graninger, M and Endmayr, V and Kühner, LM and Berger, SM and Rommer, P and Klotz, S and Gelpi, E and Vietzen, H and Höftberger, R and Puchhammer-Stöckl, E}, title = {Association Between NK Cell Genetic Variants and the Development of Long COVID Associated- and Prepandemic Small Fiber Neuropathy.}, journal = {Journal of medical virology}, volume = {96}, number = {12}, pages = {e70091}, pmid = {39610330}, issn = {1096-9071}, support = {//The study was supported by Medical and Scientific Fund of the Mayor of the Federal Capital of Vienna, Austria and Center for Virology, Medical University of Vienna, Austria./ ; }, mesh = {Humans ; *COVID-19/immunology/genetics/virology ; *Killer Cells, Natural/immunology ; Male ; Middle Aged ; Female ; Aged ; *Small Fiber Neuropathy/genetics/immunology ; SARS-CoV-2/immunology ; Adult ; NK Cell Lectin-Like Receptor Subfamily C/genetics ; Receptors, IgG/genetics ; Cytomegalovirus/immunology/genetics ; Genetic Variation ; }, abstract = {Long coronavirus disease 2019 (COVID) (LC) symptoms including pain and autonomic dysfunction are in some patients associated with small-fiber neuropathy (SFN). The pathomechanisms underlying SFN are mostly unclear. Natural killer (NK) cells play a crucial role in immune regulation, viral clearance and nerve metabolism. The aim of this study was to identify associations between development of small-fiber dysfunction dependent and independent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and human genetic markers associated with specific NK cell functions. The genetic markers assessed in all cohorts included: FCGR3A, IGHG1, HLA-E, NKG2C, and rs9916629. Genotyping was performed using TaqMan assays, Sanger sequencing and touchdown polymerase chain reaction. We assessed human cytomegalovirus (HCMV) IgG serostatus in all participants, and screened for anti-neuronal, anti-glial and anti-ganglioside autoantibodies in both patient cohorts. We included 50 LC patients with newly-emerged symptoms of small-fiber dysfunction after SARS-CoV-2 infection, 27 prepandemic SFN patients and 320 control persons. Markers associated with low NKG2C response, that is, deletion of the NKG2C gene and lack of prior HCMV infection (IgG seronegativity), occurred significantly more frequently in prepandemic SFN patients compared to LC patients and controls (p = 0.0109 and 0.0005, respectively). In conclusion, markers of impaired NKG2C pathways are associated with prepandemic SFN, but not with Long COVID-associated small-fiber dysfunction.}, } @article {pmid39609032, year = {2024}, author = {Stevenson, FA and Pfeffer, P and Walker, S and Ismaila, H and Jegatheesan, V and Mohammad, I and Blandford, A and Linke, S and Hurst, JR and Ricketts, W and Hamilton, FL and Sunkersing, D and Bradbury, K and Goodfellow, H}, title = {Using normalisation process theory to evaluate the implementation of a digital health intervention in community and secondary care long COVID clinics.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e092824}, pmid = {39609032}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; *Secondary Care/organization & administration ; *Telemedicine/organization & administration ; Qualitative Research ; SARS-CoV-2 ; Community Health Services/organization & administration ; Post-Acute COVID-19 Syndrome ; Self-Management/methods ; Mobile Applications ; Digital Health ; }, abstract = {OBJECTIVES: The potential and expected benefits of digital health interventions (DHI) have long been discussed, yet substantial challenges are associated with deploying DHI at scale. Insights are presented concerning the implementation of a DHI consisting of a patient-facing app and a digital dashboard for clinicians providing supported self-management for long COVID to support both clinicians and patients.

DESIGN: Qualitative reflexive thematic analysis, mapped against Normalisation Process Theory.

SETTING: Fifty-five and a half hours of zoom recordings of meetings between clinicians in community and secondary care long COVID clinics and members of the research team.

PARTICIPANTS: Allied health professionals, service delivery managers and members of the core team, including representatives from industry partners.

RESULTS: The DHI fitted with contextual circumstances and the design supported flexibility to suit circumstances in different trusts. The DHI also aligned with existing ways of working.Healthcare professionals worked together to support the implementation of the DHI, requiring flexibility to take account of local circumstances. The DHI was appraised in both positive and negative terms by healthcare professionals. Using DHIs was said to have the potential to complement care but not be a replacement for face-to-face clinical input. The DHI was judged to have demonstrated the potential to affect long-established patterns and organisational structures of engagement between healthcare professionals and patients in terms of access to care.

CONCLUSIONS: NPT provided a framework for considering both individual agency and the organisation context, enabling reflections to be made at the level of the structure of services as well as people's experiences. The discipline of considering first the context, then the work and finally the practical effects helped place order on the 'mess' involved in the rapid cycle of developing, refining and implementing a DHI in an atypical environment (a pandemic).}, } @article {pmid39609006, year = {2024}, author = {Amah, A and Kumar, P and Ejalonibu, H and Chavda, B and Aburub, A and Greene, R and Kemp, D and Frederick, DE and Mazurik, K and , and Slagerman, S and Dumitrescu, DI and Groot, G}, title = {Development of a minimum data set for long COVID: a Delphi study protocol.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e090304}, pmid = {39609006}, issn = {2044-6055}, mesh = {Humans ; *Delphi Technique ; *COVID-19/epidemiology ; *Quality of Life ; Canada/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Research Design ; Consensus ; }, abstract = {INTRODUCTION: Previous consensus-based long COVID research has focused on establishing research priorities, developing clinical definitions, core outcomes and a list of recommendations of patient-reported outcome measures that can be used to assess and characterise long COVID. Complementing and extending this work, the proposed study will bring together diverse knowledge users to prioritise concepts of care, quality of life and symptoms to inform a national patient registry on long COVID.

METHODS AND ANALYSIS: We will conduct a Delphi process involving Canadians with lived experiences and/or professional expertise with long COVID (including clinicians, policymakers, caregivers and community leaders). A pool of long COVID survey questions has been established through an environmental scan; these questions were coded by topic and will be presented via a series of online, anonymous survey questionnaires to a diverse cohort of 100 participants. Over the course of three Delphi rounds, participants will prioritise and recommend topics related to care, quality of life and symptoms. We will use the prioritised topics to develop a list of core questions as a minimum data set to standardise data collection and inform a national patient registry on long COVID in Canada.

ETHICS AND DISSEMINATION: This study has been approved by the University of Saskatchewan Behavioural Research Ethics Board (BEH #4296). Findings will be shared at national conferences and will be published in an open-access peer-reviewed journal. In addition, the minimum data set will be shared with key knowledge users as recommendations to inform a national long COVID patient registry.}, } @article {pmid39607208, year = {2024}, author = {Sakamoto, JS and Lopes-Santos, LE and Lacerda, KJCC and Trevisan, AC and Alexandre-Santos, L and Fukumori, OY and Bellissimo-Rodrigues, F and Wichert-Ana, L}, title = {Changes in cerebral glucose metabolism among mild long COVID patients: an [18F]FDG PET/CT study.}, journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas}, volume = {57}, number = {}, pages = {e14228}, pmid = {39607208}, issn = {1414-431X}, mesh = {Humans ; *COVID-19/diagnostic imaging/metabolism ; *Fluorodeoxyglucose F18 ; *Positron Emission Tomography Computed Tomography ; Male ; Female ; Middle Aged ; *Glucose/metabolism ; *Brain/metabolism/diagnostic imaging ; *Radiopharmaceuticals ; Adult ; SARS-CoV-2 ; Aged ; Case-Control Studies ; }, abstract = {COVID-19, caused by SARS-CoV-2, presents diverse symptoms, including neurological manifestations. This study investigated COVID-19's neurological sequelae, focusing on the central nervous system's involvement through cerebral glycolytic metabolism assessed via PET/CT. Twenty-two patients with mild long COVID cognitive symptoms and 20 healthy volunteers without cognitive, psychiatric, or neurological impairments and no history of COVID-19 infection underwent cerebral PET/CT scans using [18F]FDG to assess cerebral metabolism. The study meticulously evaluated the uptake of [18F]FDG in various brain regions, employing the CortexID Suite software for quantitative analysis. The analysis focused on identifying areas of hypometabolism and hypermetabolism, indicative of altered glucose metabolism possibly related to COVID-19's neurological impact. No statistically significant differences were found between the mild COVID and healthy groups. Although our sample was too small to generate a statistical difference between groups, future studies should explore some findings, such as hypometabolism in 15 regions and hypermetabolism in 11 regions in the mild COVID group. These changes, especially in areas linked to executive functions, sensory perception, and emotional regulation, suggest nuanced alterations in brain function. Our study did not find significant glycolytic metabolic changes in patients with mild long COVID. However, areas of glycolytic hypometabolism and hypermetabolism found in some patients showed biological plausibility with the cognitive and affective symptoms they presented. Future investigations with a larger sample size should be correlated with neuropsychological and neuropsychiatric examinations to confirm this relationship.}, } @article {pmid39606594, year = {2024}, author = {Nolberczak, D and Lesiak, A and Czajkowski, R and Bednarski, IA and Narbutt, J}, title = {LED-emitted blue light improves quality of life and reduces fatigue after COVID-19 infection.}, journal = {Postepy dermatologii i alergologii}, volume = {41}, number = {5}, pages = {515-520}, pmid = {39606594}, issn = {1642-395X}, abstract = {INTRODUCTION: Despite multiple clinical presentations of long COVID, the most common symptom encountered by the patients is fatigue which significantly impacts daily functioning and quality of life. There are, however, multiple unanswered questions regarding the treatment of fatigue among long COVID patients. Several studies highlighted that repetitive exposure to blue light may alleviate the fatigue in different groups of patients but the studies on the efficacy of blue light therapy in treatment of fatigue in long COVID patients are lacking.

AIM: To evaluate the effects of blue light therapy in treatment of fatigue among COVID-19 survivors.

MATERIAL AND METHODS: The study comprised of 43 adults who underwent COVID-19 infection with a subjective feeling of fatigue 4 weeks after the infection. All participants underwent 10 full-body blue light irradiation for 15 min a day for 5 consecutive days each week. All participants were assessed using the Fatigue Severity Scale (FSS), Short Form 36 Vitality Subscale (SF-36) and Dermatology Life Quality Index (DLQI). Serum samples were taken to measure the levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid and serotonin before and after irradiation.

RESULTS: Irradiation with blue light resulted in a significant decrease in FSS and DLQI as well as in an increase in SF-36 and serum levels of tryptophan, kynurenine and serotonin.

CONCLUSIONS: Our study shows that blue light therapy could be used as adjunctive treatment of fatigue and provide an opportunity for further scientific inquiries.}, } @article {pmid39605478, year = {2024}, author = {Maguire, C and Chen, J and Rouphael, N and Pickering, H and Phan, HV and Glascock, A and Chu, V and Dandekar, R and Corry, D and Kheradmand, F and Baden, LR and Selaky, R and McComsey, GA and Haddad, EK and Cairns, CB and Pulendran, B and Fernandez-Sesma, A and Simon, V and Metcalf, JP and Higuita, NIA and Messer, WB and David, MM and Nadeau, KC and Kraft, M and Bime, C and Schaenman, J and Erle, D and Calfee, CS and Atkinson, MA and Brackenridge, SC and Ehrlich, LIR and Montgomery, RR and Shaw, AC and Hough, CL and Geng, LN and Hafler, DA and Augustine, AD and Becker, PM and Peters, B and Ozonoff, A and Kim-Schulze, SH and Krammer, F and Bosinger, S and Eckalbar, W and Altman, MC and Wilson, M and Guan, L and Kleinstein, SH and , and Smolen, KK and Reed, EF and Levy, O and Maecker, H and Hunt, P and Steen, H and Diray-Arce, J and Langelier, CR and Melamed, E}, title = {Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39605478}, issn = {2692-8205}, support = {U19 AI090023/AI/NIAID NIH HHS/United States ; U19 AI128913/AI/NIAID NIH HHS/United States ; U19 AI118608/AI/NIAID NIH HHS/United States ; U54 AI142766/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI062629/AI/NIAID NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; U19 AI128910/AI/NIAID NIH HHS/United States ; R01 AI104870/AI/NIAID NIH HHS/United States ; T32 DA018926/DA/NIDA NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01 AI145835/AI/NIAID NIH HHS/United States ; R01 AI122220/AI/NIAID NIH HHS/United States ; U19 AI077439/AI/NIAID NIH HHS/United States ; R01 AI135803/AI/NIAID NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, abstract = {Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested that SARS-CoV-2 infection can lead to reactivation of latent viruses such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent and impact of viral reactivation in COVID-19 and its effect on the host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis of viral reactivation of all known chronically infecting viruses in 1,154 hospitalized COVID-19 patients, from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, who were followed prospectively for twelve months. We reveal significant reactivation of Herpesviridae, Enteroviridae, and Anelloviridae families during acute stage of COVID-19 (0-40 days post-hospitalization), each exhibiting distinct temporal dynamics. We also show that viral reactivation correlated with COVID-19 severity, demographic characteristics, and clinical outcomes, including mortality. Integration of cytokine profiling, cellular immunophenotyping, metabolomics, transcriptomics, and proteomics demonstrated virus-specific host responses, including elevated pro-inflammatory cytokines (e.g. IL-6, CXCL10, and TNF), increased activated CD4+ and CD8+ T-cells, and upregulation of cellular replication genes, independent of COVID-19 severity and SARS-CoV-2 viral load. Notably, persistent Anelloviridae reactivation during convalescence (≥3 months post-hospitalization) was associated with Post-Acute Sequelae of COVID-19 (PASC) symptoms, particularly physical function and fatigue. Our findings highlight a remarkable prevalence and potential impact of chronic viral reactivation on host responses and clinical outcomes during acute COVID-19 and long term PASC sequelae. Our data provide novel immune, transcriptomic, and metabolomic biomarkers of viral reactivation that may inform novel approaches to prognosticate, prevent, or treat acute COVID-19 and PASC.}, } @article {pmid39604990, year = {2024}, author = {Stubbs, E and Exley, J and Wittenberg, R and Mays, N}, title = {How to establish and sustain a disease registry: insights from a qualitative study of six disease registries in the UK.}, journal = {BMC medical informatics and decision making}, volume = {24}, number = {1}, pages = {361}, pmid = {39604990}, issn = {1472-6947}, support = {PR-PRU-1217-20602//National Institute for Health and Care Research/ ; PR-PRU-1217-20602//National Institute for Health and Care Research/ ; PR-PRU-1217-20602//National Institute for Health and Care Research/ ; PR-PRU-1217-20602//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Registries ; United Kingdom ; *COVID-19/epidemiology ; *Qualitative Research ; Chronic Disease ; }, abstract = {BACKGROUND: The advent of new chronic conditions such as long COVID-19 raises the question of whether and, if so, how best to establish new disease registries for such conditions. Prompted by the potential need for a long COVID-19 registry, we examined experiences of existing UK disease registries to understand barriers and enablers to establishing and sustaining a register, and how these have changed over time.

METHODS: We undertook semi-structured interviews between November 2022 and April 2023 with individuals representing six disease registries that collect individual-level longitudinal data on people diagnosed with a chronic condition.

RESULTS: Registries examined were developed by a few individuals, usually clinicians, to gain a greater understanding of the disease. Patient voices were largely absent from initial agenda setting processes, but, over time, all registries sought to increase patient involvement. Securing long-term funding was cited as the biggest challenge; due to limited funds, one of the registries examined no longer actively recruits patients. Charities devoted to the diseases in question were key funders, though most registries also sought commercial opportunities. Inclusion on the NIHR Clinical Research Network Portfolio was also considered a vital resource to support recruitment and follow-up of participants. All registries have sought to minimise the primary data collected to reduce the burden on clinicians and patients, increasingly relying on linkage to other data sources. Several registries have developed consent procedures that enable participants to be contacted for additional data collection. In some cases, the initial patient consent and data sharing permissions obtained had limited the flexibility to adapt the registry to changing data needs. Finally, there was a need to foster buy-in from the community of patients and clinicians who provide and/or use the data.

CONCLUSION: We identified six key considerations when establishing a sustainable disease registry: (1) include a diverse set of stakeholders; (2) involve patients at every stage; (3) collect a core data set for all participants; (4) ensure the data system is flexible and interoperable with the wider data landscape; (5) anticipate changing data needs over time; and (6) identify financial opportunities to sustain the registry's activities for the long term.}, } @article {pmid39604988, year = {2024}, author = {Cordelli, E and Soda, P and Citter, S and Schiavon, E and Salvatore, C and Fazzini, D and Clementi, G and Cellina, M and Cozzi, A and Bortolotto, C and Preda, L and Francini, L and Tortora, M and Castiglioni, I and Papa, S and Sona, D and Alì, M}, title = {Machine learning predicts pulmonary Long Covid sequelae using clinical data.}, journal = {BMC medical informatics and decision making}, volume = {24}, number = {1}, pages = {359}, pmid = {39604988}, issn = {1472-6947}, mesh = {Humans ; *Machine Learning ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Male ; Female ; Middle Aged ; }, abstract = {Long COVID is a multi-systemic disease characterized by the persistence or occurrence of many symptoms that in many cases affect the pulmonary system. These, in turn, may deteriorate the patient's quality of life making it easier to develop severe complications. Being able to predict this syndrome is therefore important as this enables early treatment. In this work, we investigated three machine learning approaches that use clinical data collected at the time of hospitalization to this goal. The first works with all the descriptors feeding a traditional shallow learner, the second exploits the benefits of an ensemble of classifiers, and the third is driven by the intrinsic multimodality of the data so that different models learn complementary information. The experiments on a new cohort of data from 152 patients show that it is possible to predict pulmonary Long Covid sequelae with an accuracy of up to 94 % . As a further contribution, this work also publicly discloses the related data repository to foster research in this field.}, } @article {pmid39604720, year = {2024}, author = {Chakraborty, C and Bhattacharya, M and Alshammari, A and Albekairi, NA and Lee, SS}, title = {Mapping the Potential Genes and Associated Pathways Involved in Long COVID-Associated Brain Fog Using Integrative Bioinformatics and Systems Biology Strategy.}, journal = {Molecular biotechnology}, volume = {}, number = {}, pages = {}, pmid = {39604720}, issn = {1559-0305}, abstract = {One of the recent emerging global health issues is long COVID. Among long COVID patients, long COVID-associated brain fog is an important area. We noted an immense gap in understanding the genes and associated pathways involved in long COVID-associated brain fog. Therefore, the study has been selected to understand the genes and pathways involved in patients with long COVID-associated brain fog. A GEO dataset, which was developed through the RNA-seq, was used for the analysis. The dataset encompasses 22 human samples of PBMC. The dataset (human samples of PBMC) was grouped into four cohorts for this study: healthy cohort, COVID convalescent, long COVID, and long COVID brain fog. Therefore, the selection criteria for the 22 PBMC samples were based on the individual infection type (COVID convalescent, long COVID, and long COVID brain fog) and the healthy cohort. Using DEG profile evaluation, we revealed 250 top-ranked DEGs with P values, Padj, baseMean, etc. From the top-ranked DEGs, we listed 24 significant DEGs and some significant DEGs are SMAD3 (P value = 6.34e-07), PF4 (P value = 1.88e-05), TNFAIP3 (P value = 3.70e-06), CXCL5 (P value = 1.22e-08), etc. Among the top-ranked DEGs, we found some genes linked with different biological functions, such as inflammatory cytokine secretion, inflammation, microclot formation, and BBB disruption. From our investigation, we found some genes that are associated with this condition, namely PF4, SMAD3, CXCL5, TNFAIP3, etc. From the literature survey and functional pathway enrichment analysis, we noted the function of the genes such as PF4, SMAD3, and CXCL5. We found that PF4 assists in clot formation, and SMAD3 is associated with neuroinflammation. Similarly, CXCL5 is an inflammatory marker associated with neuroinflammation and BBB damage. At the same time, the study with functional pathway enrichment analysis reflects that DEGs of long COVID-related brain fog might be associated with several biological pathways and processes, cell signatures, and gene-disease associations. It reflects that the disease is a highly complex one. Our study will provide an understanding of the genes and associated pathways in long COVID-related brain fog, which will assist in the next-generation biomarker discovery and therapeutics for these patients.}, } @article {pmid39603702, year = {2024}, author = {Zeraatkar, D and Ling, M and Kirsh, S and Jassal, T and Shahab, M and Movahed, H and Talukdar, JR and Walch, A and Chakraborty, S and Turner, T and Turkstra, L and McIntyre, RS and Izcovich, A and Mbuagbaw, L and Agoritsas, T and Flottorp, SA and Garner, P and Pitre, T and Couban, RJ and Busse, JW}, title = {Interventions for the management of long covid (post-covid condition): living systematic review.}, journal = {BMJ (Clinical research ed.)}, volume = {387}, number = {}, pages = {e081318}, pmid = {39603702}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/rehabilitation/therapy/complications ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cognitive Behavioral Therapy/methods ; Randomized Controlled Trials as Topic ; Exercise ; }, abstract = {OBJECTIVE: To compare the effectiveness of interventions for the management of long covid (post-covid condition).

DESIGN: Living systematic review.

DATA SOURCES: Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.

ELIGIBILITY CRITERIA: Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.

RESULTS: 24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation. Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference -8.4, 95% confidence interval (CI) -13.11 to -3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference -5.2, -7.97 to -2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment). Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference -1.50, -2.41 to -0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range -0.022-1; higher scores indicate less impairment). Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment). No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.

CONCLUSION: Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.

Open Science Framework https://osf.io/9h7zm/.

READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.}, } @article {pmid39603665, year = {2024}, author = {Gardiner, L and Young, HML and Drover, H and Morgan-Selvaratnam, E and Natt, M and Smith, N and Daynes, E and Orme, MW and Taylor, RS and Singh, SJ and Evans, RA}, title = {Reporting of pre-existing multiple long-term conditions in physical rehabilitation for long COVID: a scoping review.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {33}, number = {174}, pages = {}, pmid = {39603665}, issn = {1600-0617}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Physical Therapy Modalities ; SARS-CoV-2 ; Time Factors ; Chronic Disease ; Treatment Outcome ; }, abstract = {BACKGROUND: Physical rehabilitation may improve health and wellbeing outcomes for some adults living with long COVID. However, individuals living with pre-existing multiple long-term conditions (MLTCs) and long COVID may have additional rehabilitation challenges. This scoping review aims to identify the available evidence describing physical rehabilitation interventions for adults living with long COVID, to systematically map the reporting of pre-existing MLTCs, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing long-term conditions (LTCs) and long COVID.

METHODS: MEDLINE, CINAHL, Scopus, APA PsycInfo, medRxiv, OpenGrey and MedNar were searched from January 2020 to July 2023. Eligibility criteria included adults with long COVID, rehabilitation interventions including a physical component in any setting and any study design investigating interventions or intervention content except case series/reports.

RESULTS: Of 5326 unique records, 50 articles met the inclusion criteria, of which 25 (50%) made reference to pre-existing LTCs. These articles included four protocols and one consensus statement. Four of the remaining 20 studies (20%) reported the number of pre-existing LTCs, enabling the differentiation of individuals with MLTCs. One study reported outcomes of individuals with MLTCs separately to those without. The interventions described (k=24) typically consisted of combined aerobic and strength exercises (k=17 (71%)) in an outpatient setting (k=13 (54%)).

CONCLUSIONS: There is limited and inconsistent reporting of the presence of MLTCs in studies of physical rehabilitation for adults with long COVID. Clarity and consistency of reporting of MLTCs is required to enable evaluation and adaptation of interventions to improve health and wellbeing for this population.}, } @article {pmid39603265, year = {2024}, author = {Mu, Y and Dashtban, A and Mizani, MA and Tomlinson, C and Mohamed, M and Ashworth, M and Mamas, M and Priedon, R and Petersen, S and Kontopantelis, E and Horstmanshof, K and Pagel, C and Hocaoğlu, M and Khunti, K and Williams, R and Thygesen, J and Lorgelly, P and Gomes, M and Heightman, M and Banerjee, A and , }, title = {Healthcare utilisation of 282,080 individuals with long COVID over two years: a multiple matched control, longitudinal cohort analysis.}, journal = {Journal of the Royal Society of Medicine}, volume = {117}, number = {11}, pages = {369-381}, pmid = {39603265}, issn = {1758-1095}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Male ; Female ; Middle Aged ; Aged ; Case-Control Studies ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Longitudinal Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; Primary Health Care/statistics & numerical data ; Aged, 80 and over ; Health Care Costs/statistics & numerical data ; Pandemics ; Hospitalization/statistics & numerical data ; Cohort Studies ; }, abstract = {OBJECTIVES: To investigate healthcare utilisation and cost in individuals with long COVID (LC) at population level.

DESIGN: Case-control cohort analysis with multiple age-, sex-, ethnicity-, deprivation-, region- and comorbidity-matched control groups: (1) COVID only, no LC; (2) pre-pandemic; (3) contemporary non-COVID; and (4) pre-LC (self-controlled, pre-COVID pandemic).

SETTING: National, population-based, linked UK electronic health records (British Heart Foundation/NHS England Secure Data Environment).

PARTICIPANTS: Adults aged ≥18 years with LC between January 2020 and January 2023.

MAIN OUTCOME MEASURES: Healthcare utilisation (number of consultations/visits per person: primary care (general practitioner [GP]), secondary care (outpatient [OP], inpatient [IP] and emergency department [ED], investigations and procedures) and inflation-adjusted cost (£) for LC and control populations per month, calendar year and pandemic year for each category.

RESULTS: A total of 282,080 individuals with LC were included between January 2020 and January 2023. The control groups were COVID only, no LC (n = 1,112,370), pre-pandemic (n = 1,031,285), contemporary non-COVID (n = 1,118,360) and pre-LC (n = 282,080). Healthcare utilisation per person (per month/year) was higher in LC than controls across GP, OP and ED. For IP, LC had higher healthcare utilisation than pre-LC and contemporary non-COVID (all p < 0.0001). Healthcare utilisation of the LC group increased progressively between 2020 and 2023, compared with controls. Median cost per patient/year was also higher in individuals with LC than all control groups.

CONCLUSIONS: LC has been associated with substantial, persistent healthcare utilisation and cost over the last three years. Future funding, resources and staff for LC prevention, treatment and research must be prioritised to reduce sustained primary and secondary healthcare utilisation and costs.}, } @article {pmid39602373, year = {2024}, author = {Connor, C and Kranert, M and Mckelvie, S and Clutterbuck, D and McFarland, S and Alwan, NA}, title = {A critical analysis of UK media characterisations of Long Covid in children and young people.}, journal = {PLOS global public health}, volume = {4}, number = {11}, pages = {e0003126}, pmid = {39602373}, issn = {2767-3375}, abstract = {Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice. We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were unmentioned. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologising Long Covid, and overemphasised psychological components. CYP were rarely consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promotes stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents' credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists.}, } @article {pmid39601588, year = {2024}, author = {Saucy, A and Espinosa, A and Iraola-Guzmán, S and Castaño-Vinyals, G and Harding, BN and Karachaliou, M and Ranzani, O and De Cid, R and Garcia-Aymerich, J and Kogevinas, M}, title = {Environmental Exposures and Long COVID in a Prospective Population-Based Study in Catalonia (COVICAT Study).}, journal = {Environmental health perspectives}, volume = {132}, number = {11}, pages = {117701}, pmid = {39601588}, issn = {1552-9924}, } @article {pmid39600394, year = {2024}, author = {Ismaila, H and Blandford, A and Sunkersing, D and Stevenson, F and Goodfellow, H}, title = {Comparative insights into clinic onboarding and interaction practices for patient engagement in long COVID digital health care.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241294101}, pmid = {39600394}, issn = {2055-2076}, abstract = {OBJECTIVES: This study explores the influence of clinic-led onboarding and interaction processes on patient engagement within a digital health program for long COVID care, the Living with COVID Recovery (LWCR) program. We compared clinical practices and patient engagement levels across seven clinics utilising LWCR, gaining insights that could optimise digital health interventions (DHIs) for long COVID care.

METHODS: Using a mixed-methods approach, we conducted qualitative interviews with clinicians from seven clinics (out of thirty five) to understand their onboarding and interaction strategies for the LWCR program. We also performed a descriptive quantitative analysis of patient and clinic usage data to rank and classify patient engagement. These rankings were then compared against qualitative insights to explore the influence of clinic-led strategies on patient engagement. Additionally, we conducted interviews with 12 patients under the care of seven clinics to complement our mixed-method analysis.

RESULTS: Four key practices were identified in clinics with higher patient engagement: pre-assessment onboarding, proactive communication, patient education and the involvement of clinically experienced staff. Clinics that integrated these interdependent practices into a cohesive strategy demonstrated notably higher patient engagement levels.

CONCLUSION: This study highlights the critical role of integrating multiple, interdependent clinic-led strategies to optimise patient engagement in DHIs, particularly for long COVID care. These findings provide actionable insights for healthcare providers and policymakers, suggesting that a comprehensive approach is essential for maximising patient engagement and improving care outcomes. The study lays the groundwork for future research to explore the broader applicability of these strategies across different healthcare contexts.}, } @article {pmid39600184, year = {2024}, author = {Merhavy, ZI and Junor, T and Gonzalez, A and De Filippis, SM and Oveisitork, S and Rivera, E and Ndukwu, I and Bhatara, K}, title = {Long COVID: A Comprehensive Overview of the Signs and Symptoms across Multiple Organ Systems.}, journal = {Korean journal of family medicine}, volume = {45}, number = {6}, pages = {305-316}, pmid = {39600184}, issn = {2005-6443}, abstract = {Long coronavirus disease (COVID), also known as the post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), is a significant concern since the end of the COVID-19 pandemic, as it still manifests in individuals with persistent symptoms and complications beyond the acute phase of infection. Defining this disease is challenging, as it manifests as a spectrum of symptoms varying in severity among individuals who have previously tested positive for COVID-19. Long COVID is more prevalent in hospitalized COVID-19 patients and presents in various ways, ranging from pulmonary to extrapulmonary symptoms. This literature review examines the current body of research on long COVID with a focus on its effects on the cardiovascular, hematological, respiratory, renal, and neurological systems with systematically analyzed, peer-reviewed articles retrieved from the PubMed database. There have been several proposed pathophysiological mechanisms by which severe acute respiratory syndrome coronavirus 2 affects the aforementioned organ systems; however, research on the definite mechanisms is lacking, especially when considering the management of long COVID in the perioperative setting. The impact of post-COVID sequelae necessitates individualized management strategies tailored to each symptomatic profile, particularly in patients with comorbidities. The COVID-19 pandemic affected millions of people and had a profound impact on those who developed PASC, lowering their quality of life and increasing potential surgical risks. However, there is still uncertainty regarding the specific risk factors for long COVID and who is most susceptible to it. Further research is required to fill these gaps and explore potential avenues for preventing PASC.}, } @article {pmid39599909, year = {2024}, author = {Livieratos, A and Gogos, C and Akinosoglou, K}, title = {Beyond Antivirals: Alternative Therapies for Long COVID.}, journal = {Viruses}, volume = {16}, number = {11}, pages = {}, pmid = {39599909}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; Metformin/therapeutic use ; COVID-19 Drug Treatment ; Anti-Inflammatory Agents/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use ; Fatty Acids, Omega-3/therapeutic use ; Dexamethasone/therapeutic use ; Naltrexone/therapeutic use ; }, abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is a condition characterized by numerous lingering symptoms that persist for weeks to months following the viral illness. While treatment for PASC is still evolving, several therapeutic approaches beyond traditional antiviral therapies are being investigated, such as immune-modulating agents, anti-inflammatory drugs, and various supportive interventions focusing at alleviating symptoms and enhancing recovery. We aimed to summarize the breadth of available evidence, identify knowledge gaps, and highlight promising non-antiviral therapies for Long COVID/PASC. We followed the framework of a scoping methodology by mapping existing evidence from a range of studies, including randomized clinical trials, observational research, and case series. Treatments evaluated include metformin, low-dose naltrexone (LDN), dexamethasone, statins, omega-3 fatty acids, L-arginine, and emerging therapies like intravenous immunoglobulin (IVIg) and therapeutic apheresis. Early findings suggest that metformin has the strongest clinical evidence, particularly from large phase 3 trials, while LDN and dexamethasone show potential based on observational studies. However, many treatments lack robust, large-scale trials. This review emphasizes the need for further research to confirm the efficacy of these treatments and guide clinical practice for Long COVID management.}, } @article {pmid39599883, year = {2024}, author = {Mendes, LT and Gama-Almeida, MC and Reis, DL and Silva, ACPE and Neris, RLS and Galliez, RM and Castiñeiras, TMPP and On Behalf Of The Ufrj Covid-Working Group, and Ludwig, C and Valente, AP and Costa Dos Santos Junior, G and El-Bacha, T and Assunção-Miranda, I}, title = {Longitudinal [1]H NMR-Based Metabolomics in Saliva Unveils Signatures of Transition from Acute to Post-Acute Phase of SARS-CoV-2 Infection.}, journal = {Viruses}, volume = {16}, number = {11}, pages = {}, pmid = {39599883}, issn = {1999-4915}, support = {E-26/210.658/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/211.509/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/201.152/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/210.785/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 01.20.0029.000462/20//Financiadora de Estudos e Projetos/ ; 404096/2020-4//National Council for Scientific and Technological Development/ ; }, mesh = {Humans ; *COVID-19/metabolism/virology ; Male ; *Saliva/metabolism/virology ; Female ; *Metabolomics/methods ; Adult ; *SARS-CoV-2 ; Middle Aged ; Proton Magnetic Resonance Spectroscopy/methods ; Longitudinal Studies ; Metabolome ; Viral Load ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a [1]H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH3)3 choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.}, } @article {pmid39599809, year = {2024}, author = {Alghamdi, F and Mokbel, K and Meertens, R and Obotiba, AD and Alharbi, M and Knapp, KM and Strain, WD}, title = {Bone Mineral Density, Bone Biomarkers, and Joints in Acute, Post, and Long COVID-19: A Systematic Review.}, journal = {Viruses}, volume = {16}, number = {11}, pages = {}, pmid = {39599809}, issn = {1999-4915}, mesh = {Humans ; *COVID-19 ; *Bone Density ; *Biomarkers ; *SARS-CoV-2 ; Joints/virology ; Osteoporosis/metabolism ; Bone and Bones/metabolism/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 is highly transmissible and affects the respiratory system. People with COVID-19 are at higher risk of physical and mental health conditions, which could impact bone health. The aim of this review was to explore the effects of COVID-19 on BMD, BTMs, and joints. An electronic search of the PubMed, Web of Science, Scopus, and Ovid Medline databases considered studies published between 1 January 2020 and 1 November 2023. The search was limited to English, original studies in adult humans. The title and abstract of the identified papers were screened, followed by a full-text review using inclusion and exclusion criteria. The data extracted included the study and participant characteristics, BTMs, BMD, and joint abnormalities. The Newcastle-Ottawa scale quality assessment tool was used to assess the risk of bias. Five studies involving 305 out of 495 infected individuals observed a reduced BMD after COVID-19, with the most significant reduction occurring a year later. Both bone resorption and bone formation markers decreased, while regulatory markers showed higher levels in infected patients. COVID-19 may harm bone health by increasing bone regulatory markers and reducing bone formation and absorption, leading to a lower BMD. Elderly, frail, and osteopenic or osteoporotic individuals are at higher risk and should be regularly monitored for bone loss if they have long COVID.}, } @article {pmid39598316, year = {2024}, author = {Bejan, I and Popescu, CP and Ruta, SM}, title = {Insights into the Risk Factors and Outcomes of Post-COVID-19 Syndrome-Results from a Retrospective, Cross-Sectional Study in Romania.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {39598316}, issn = {2075-1729}, abstract = {Post-Coronavirus Disease 2019 (post-COVID-19) syndrome represents a cluster of persistent symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that can severely affect quality of life. The pathogenic mechanisms and epidemiology in different regions are still under evaluation. To assess the outcomes of post-COVID-19 syndrome, we performed a questionnaire-based, cross-sectional study in previously infected individuals. Out of 549 respondents, (male:female ratio: 0.32), 29.5% had persistent symptoms at 3 months, 23.5% had persistent symptoms at 6 months, and 18.3% had persistent symptoms at 12 months after the initial infection. The most common symptoms included fatigue (8.7%), sleep disturbances (7.1%), and cognitive impairment (6.4%). The risk of developing post-COVID-19 syndrome increased for those with more symptoms in the acute phase (OR 4.24, p < 0.001) and those experiencing reinfections (OR 2.405, p < 0.001), while SARS-CoV-2 vaccination halved the risk (OR = 0.489, p = 0.004). Individuals with post-COVID-19 syndrome had a 5.7-fold higher risk of being diagnosed with a new chronic condition, with 44% reporting cardiovascular disease, and a 6.8-fold higher likelihood of needing medical care or leave. Affected individuals reported significant impairments in mobility, pain/discomfort, and anxiety/depression, with 20.7% needing to adjust their work schedules. Overall, patients with post-COVID-19 syndrome require ongoing monitoring and rehabilitation, and further socio-economic impact studies are needed.}, } @article {pmid39597960, year = {2024}, author = {Chowdary, H and Riley, N and Patel, P and Gossweiler, AG and Running, CA and Srinivasan, M}, title = {Reduced Salivary Gustin and Statherin in Long-COVID Cohort with Impaired Bitter Taste.}, journal = {Journal of clinical medicine}, volume = {13}, number = {22}, pages = {}, pmid = {39597960}, issn = {2077-0383}, support = {44-761-54//Delta Dental Research Foundation/ ; }, abstract = {Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While the majority of those affected reported recovery over time, emerging data suggest that 20-25% of individuals experience persistent taste dysfunction, constituting a common symptom of long COVID. Gustation is mediated by continuously renewing taste bud cells. A balance between the counteracting processes of cell generation and cell death maintains the homeostatic turnover. Sonic hedgehog (SHH) is a morphogenic protein that promotes taste cell proliferation and differentiation. Enzymatic proteins such as gustin modulate the environment around the taste receptors and influence taste perception. Hence, we hypothesized that increased taste cell turnover and reduced taste-related salivary proteins contribute to the taste dysfunction in long COVID. Methods: Unstimulated whole saliva (UWS) was collected from individuals with long COVID experiencing taste dysfunction after obtaining informed consent. The normal control included archived saliva samples catalogued prior to 2019. Taste perception was objectively determined by the waterless empirical taste test. The SHH, gustin, and inflammatory cytokines in UWS were determined with ELISA. The expressions of epithelial and taste-cell-specific markers in cellular saliva were assessed by immunoflurorescence. Results: Impaired bitter taste was the most common dysfunction in the long-COVID cohort. Salivary gustin was significantly lower in those with long COVID and correlated with lower bitter taste score. Cellular saliva showed keratin-10- and small-proline-rich protein-positive epithelial cells as well as SHH-, occluding- and KCNQ1-positive taste cells. Conclusions: Salivary gustin could be a marker for impaired bitter taste in long COVID.}, } @article {pmid39597891, year = {2024}, author = {Trimble, KZ and Switzer, JN and Blitshteyn, S}, title = {Exercise in Postural Orthostatic Tachycardia Syndrome: Focus on Individualized Exercise Approach.}, journal = {Journal of clinical medicine}, volume = {13}, number = {22}, pages = {}, pmid = {39597891}, issn = {2077-0383}, abstract = {Exercise is a vital component of health and is commonly utilized as a non-pharmacologic therapy for many disorders, including postural orthostatic tachycardia syndrome (POTS). However, exercise intolerance is a key feature of POTS and other autonomic disorders and, therefore, presents a major barrier for many patients. Despite exercise being uniformly recommended as a therapeutic intervention, a majority of patients with POTS, especially those with severe orthostatic intolerance and fatigue, are unable to complete or sustain rigorous exercise programs or successfully integrate them into their daily routine. In this narrative review, we discuss the current literature on exercise and POTS and our clinical experience with a home-based exercise approach developed at the Dysautonomia Clinic. We conclude that individualized exercise programs that are delivered remotely by a certified physical therapist may be convenient, easily accessible, and safe for patients with POTS, especially those with severe symptoms who may be home- or bedbound. Future randomized controlled studies are needed to quantify and characterize the benefits of home-based exercise programs delivered remotely compared to standard therapy.}, } @article {pmid39596903, year = {2024}, author = {Grau, M and Presche, A and Krüger, AL and Bloch, W and Haiduk, B}, title = {Red Blood Cell Morphology Is Associated with Altered Hemorheological Properties and Fatigue in Patients with Long COVID.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596903}, issn = {2079-7737}, support = {No grant number provided//S.P.O.R.T. Institut/ ; }, abstract = {BACKGROUND: SARS-CoV-2 infection adversely affects rheological parameters, particularly red blood cell (RBC) aggregation and deformability, but whether these changes persist in patients suffering from Long-COVID (LC) and whether these changes are related to RBC morphology remain unknown.

METHODS: Venous blood was collected from n = 30 diagnosed LC patients and n = 30 non-LC controls and RBC deformability, RBC aggregation, and hematological parameters were measured. In addition, RBCs were examined microscopically for morphological abnormalities. The mechanical sensitivity index (MS) was assessed in n = 15 LC and n = 15 non-LC samples.

RESULTS: Hematological parameters did not differ between the groups. However, LC showed higher aggregation-related parameters. Although RBC deformability was higher in LC, MS, reflecting the functional capacity to deform, was limited in this group. RBCs from LC showed significantly more morphological abnormalities. The extent of morphological abnormalities correlated with MS and the FACIT-Fatigue score of the LC patients.

CONCLUSION: RBCs from LC show a high degree of morphological abnormalities, which might limit the blood flow determining RBC properties and also be related to fatigue symptomatology in LC. Approaches are now needed to understand the underlying cause of these alterations and to ameliorate these permanent changes.}, } @article {pmid39596862, year = {2024}, author = {Petrella, C and Ferraguti, G and Tarani, L and Tarani, F and Messina, MP and Fiore, M}, title = {Nerve Growth Factor and Brain-Derived Neurotrophic Factor in COVID-19.}, journal = {Biology}, volume = {13}, number = {11}, pages = {}, pmid = {39596862}, issn = {2079-7737}, abstract = {Neurotrophins (NTs) constitute a family of small protein messengers that play a fundamental role in both the central and peripheral nervous systems. In particular, the nerve growth factor (NGF) and the brain-derived neurotrophic factor (BDNF) play a subtle role in the survival, differentiation, and functioning of neuronal populations, as well as in the fine regulation of immune functions. The SARS-CoV-2 infection was characterized by a sequela of symptoms (serious respiratory pathology, inflammatory storm, neurological discomfort, up to the less serious flu-like symptoms), which caused, at the end of 2023, more than 7 million deaths worldwide. Despite the official end of the pandemic, the physical and psychological consequences are currently the object of scientific research, both acute and chronic/long-lasting (Long-COVID-19). Given the multifactorial nature of the outcomes of SARS-CoV-2 infection in adults and children, several studies have investigated the potential involvement of the NGF and BDNF systems in the pathology. This narrative review aims to summarize the most recent evidence on this crucial topic.}, } @article {pmid39596552, year = {2024}, author = {Signore, IA and Donoso, G and Bocchieri, P and Tobar-Calfucoy, EA and Yáñez, CE and Carvajal-Silva, L and Silva, AX and Otth, C and Cappelli, C and Valenzuela Jorquera, H and Zapata-Contreras, D and Espinosa-Parrilla, Y and Zúñiga-Pacheco, P and Fuentes-Guajardo, M and Monardes-Ramírez, VA and Kochifas Velasquez, P and Muñoz, CA and Dorador, C and García-Araya, J and Campillay-Véliz, CP and Echeverria, C and Santander, RA and Cerpa, LC and Martínez, MF and Quiñones, LA and Lamoza Galleguillos, ER and Saez Hidalgo, J and Nova-Lamperti, E and Sanhueza, S and Giacaman, A and Acosta-Jamett, G and Verdugo, C and Plaza, A and Verdugo, C and Selman, C and Verdugo, RA and Colombo, A}, title = {The Chilean COVID-19 Genomics Network Biorepository: A Resource for Multi-Omics Studies of COVID-19 and Long COVID in a Latin American Population.}, journal = {Genes}, volume = {15}, number = {11}, pages = {}, pmid = {39596552}, issn = {2073-4425}, support = {ANID COVID0961, ANID COVID0789, ANID COVID1005, ANID COVID0585, ACT210085, FONDECYT 1170446, FONDECYT 1211480//Agencia Nacional de Investigación y Desarrollo/ ; MAG1995//Ministry of Education/ ; RED21193//Interuniversity Center for Healthy Aging/ ; VRID220.085.041-INI//University of Concepción/ ; }, mesh = {Humans ; *COVID-19/genetics/virology/epidemiology ; Chile ; *Biological Specimen Banks ; *Genomics/methods ; *SARS-CoV-2/genetics ; Male ; Female ; Adult ; Middle Aged ; Aged ; Latin America ; Multiomics ; }, abstract = {Although a lack of diversity in genetic studies is an acknowledged obstacle for personalized medicine and precision public health, Latin American populations remain particularly understudied despite their heterogeneity and mixed ancestry. This gap extends to COVID-19 despite its variability in susceptibility and clinical course, where ethnic background appears to influence disease severity, with non-Europeans facing higher hospitalization rates. In addition, access to high-quality samples and data is a critical issue for personalized and precision medicine, and it has become clear that the solution lies in biobanks. The creation of the Chilean COVID-19 Biorepository reported here addresses these gaps, representing the first nationwide multicentric Chilean initiative. It operates under rigorous biobanking standards and serves as one of South America's largest COVID cohorts. A centralized harmonization strategy was chosen and included unified standard operating procedures, a sampling coding system, and biobanking staff training. Adults with confirmed SARS-CoV-2 infection provided broad informed consent. Samples were collected to preserve blood, plasma, buffy coat, and DNA. Quality controls included adherence to the standard preanalytical code, incident reporting, and DNA concentration and absorbance ratio 260/280 assessments. Detailed sociodemographic, health, medication, and preexisting condition data were gathered. In five months, 2262 participants were enrolled, pseudonymized, and sorted by disease severity. The average Amerindian ancestry considering all participant was 44.0% [SD 15.5%], and this value increased to 61.2% [SD 19.5%] among those who self-identified as Native South Americans. Notably, 279 participants self-identified with one of 12 ethnic groups. High compliance (>90%) in all assessed quality controls was achieved. Looking ahead, our team founded the COVID-19 Genomics Network (C19-GenoNet) focused on identifying genetic factors influencing SARS-CoV-2 outcomes. In conclusion, this bottom-up collaborative effort aims to promote the integration of Latin American populations into global genetic research and welcomes collaborations supporting this endeavor. Interested parties are invited to explore collaboration opportunities through our catalog, accessible online.}, } @article {pmid39595587, year = {2024}, author = {Aziz, M and Popa, I and Zia, A and Fischer, A and Khan, SA and Hamedani, AF and Asif, AR}, title = {KnowVID-19: A Knowledge-Based System to Extract Targeted COVID-19 Information from Online Medical Repositories.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595587}, issn = {2218-273X}, support = {16KIS1292//Federal Ministry of Education and Research/ ; }, mesh = {*COVID-19/virology/epidemiology ; Humans ; *Data Mining/methods ; *SARS-CoV-2 ; *Knowledge Bases ; *Machine Learning ; Software ; PubMed ; }, abstract = {We present KnowVID-19, a knowledge-based system that assists medical researchers and scientists in extracting targeted information quickly and efficiently from online medical literature repositories, such as PubMed, PubMed Central, and other biomedical sources. The system utilizes various open-source machine learning tools, such as GROBID, S2ORC, and BioC to streamline the processes of data extraction and data mining. Central to the functionality of KnowVID-19 is its keyword-based text classification process, which plays a pivotal role in organizing and categorizing the extracted information. By employing machine learning techniques for keyword extraction-specifically RAKE, YAKE, and KeyBERT-KnowVID-19 systematically categorizes publication data into distinct topics and subtopics. This topic structuring enhances the system's ability to match user queries with relevant research, improving both the accuracy and efficiency of the search results. In addition, KnowVID-19 leverages the NetworkX Python library to construct networks of the most relevant terms within publications. These networks are then visualized using Cytoscape software, providing a graphical representation of the relationships between key terms. This network visualization allows researchers to easily track emerging trends and developments related to COVID-19, long COVID, and associated topics, facilitating more informed and user-centered exploration of the scientific literature. KnowVID-19 also provides an interactive web application with an intuitive, user-centered interface. This platform supports seamless keyword searching and filtering, as well as a visual network of term associations to help users quickly identify emerging research trends. The responsive design and network visualization enables efficient navigation and access to targeted COVID-19 literature, enhancing both the user experience and the accuracy of data-driven insights.}, } @article {pmid39595012, year = {2024}, author = {Kieffer, S and Krüger, AL and Haiduk, B and Grau, M}, title = {Individualized and Controlled Exercise Training Improves Fatigue and Exercise Capacity in Patients with Long-COVID.}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595012}, issn = {2227-9059}, abstract = {(1) Background: Long-term health effects after SARS-CoV-2 infections can manifest in a plethora of symptoms, significantly impacting the quality of life of affected individuals. (2) Aim: The present paper aimed to assess the effects of an individualized and controlled exercise intervention on fatigue and exercise capacity among Long-COVID (LC) patients in an ambulatory setting. (3) Methods: Forty-one (n = 41) LC patients performed an exercise protocol with an individualized control of the patients' training intensity during the study period based on the individual's ability to achieve the target criteria. The program was carried out two to three times a week, each session lasted 30 min, and the study parameters were recorded at the beginning of the program, as well as after 6 and 12 weeks, respectively. These included both patient-reported (PCFS questionnaire, FACIT-Fatigue questionnaire) and objective (one-minute sit-to-stand test (1MSTST), workload) outcomes. (4) Results: The exercise training intervention resulted in significant improvements in the FACIT-Fatigue (F(2, 80) = 18.08, p < 0.001), 1MSTST (χ2(2) = 19.35, p < 0.001) and workload scores (χ2(2) = 62.27, p < 0.001), while the PCFS scores remained unchanged. Changes in the workload scores were dependent on the frequency of the completed exercise sessions and were higher in the LC patients with a moderate Post COVID Syndrome Score (PCS) compared to a severe PCS. (5) Conclusions: The individualized and controlled training approach demonstrated efficacy in reducing fatigue and enhancing exercise capacity among outpatient LC patients. However, for complete regeneration, a longer, possibly indefinite, treatment is required, which in practice would be feasible within the framework of legislation.}, } @article {pmid39594500, year = {2024}, author = {Cuevas-Sierra, A and de la O, V and Higuera-Gómez, A and Chero-Sandoval, L and de Cuevillas, B and Martínez-Urbistondo, M and Moreno-Torres, V and Pintos-Pascual, I and Castejón, R and Martínez, JA}, title = {Mediterranean Diet and Olive Oil Redox Interactions on Lactate Dehydrogenase Mediated by Gut Oscillibacter in Patients with Long-COVID-19 Syndrome.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {39594500}, issn = {2076-3921}, support = {Y2020/6600//goverment of madrid/ ; }, abstract = {Chronic viral inflammation is associated with oxidative stress and changes in gut microbiota. The Mediterranean diet (MD), with recognized anti-inflammatory and antioxidant properties, modulates gut microorganisms, specifically on the interaction between extra virgin olive oil, a key component of the MD with well-documented antioxidant effects. This study investigated the influence of adherence to MD and antioxidant-rich foods (extra virgin olive oil) on biochemical, inflammatory, and microbiota profiles in patients with chronic inflammation defined as a prolonged inflammatory response due to immune dysregulation following the acute phase of the viral infection. Participants were classified into low (n = 54) and high (n = 134) MD adherence groups (cut-off of 7 points based on previous studies utilizing the same threshold in the assessment of MD adherence). Gut microbiota was sequenced using the 16S technique, and the adherence to MD was assessed using a validated questionnaire for a Spanish population. High adherence to the MD was linked to significant improvements in inflammatory and oxidative stress markers, including reductions in LDL-cholesterol, glucose, and lactate dehydrogenase (LDH) levels, an indicative of redox balance, as well as a significant higher consumption of antioxidant foods. Moreover, gut microbiota analysis revealed distinct compositional shifts and a lower abundance of the Oscillibacter genus in the high adherence group. Notably, a significant interaction was observed between MD adherence and extra virgin olive oil consumption, with Oscillibacter abundance influencing LDH levels, suggesting that the MD antioxidant properties may modulate inflammation through gut microbiota-mediated mechanisms. These findings provide new evidence that adherence to the Mediterranean diet can reduce inflammatory markers in patients with long-COVID-19, a population that has not been extensively studied, while also highlighting the potential role of the bacterial genus Oscillibacter in modulating this effect.}, } @article {pmid39592773, year = {2024}, author = {Kovács, F and Posvai, T and Zsáry, E and Kolonics, F and Garai, R and Herczeg, V and Czárán, D and Takács, J and Szabó, AJ and Krivácsy, P and Csépányi-Kömi, R}, title = {Long COVID syndrome in children: neutrophilic granulocyte dysfunction and its correlation with disease severity.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {39592773}, issn = {1530-0447}, abstract = {BACKGROUND: Many children suffer from lingering symptoms after COVID-19, known as long COVID syndrome (LCS), otherwise called Post COVID-19 Condition (PCC). Despite extensive research, the prevalence of symptoms, its impact on quality of life, and underlying mechanisms still need to be fully understood. As neutrophilic granulocytes play an essential role in COVID-19, and their prolonged disruption was found to cause immunological diseases, we hypothesized their ongoing disturbed functionality in LCS.

METHODS: We studied 129 children with LCS, 32 convalescent children (CG+), and 8 uninfected children (CG-). Online questionnaires and in-person examinations assessed symptoms, quality of life, and functioning (QoL-F). Effector functions of neutrophilic granulocytes obtained from the venous blood of 29 LCS and 17 CG+ children were also investigated.

RESULTS: Persistent fatigue was the most common symptom in children with LCS, while both control groups complained about anxiety most frequently. LCS children experienced significantly more symptoms, impairing their QoL-F compared to CG+. Neutrophilic granulocyte dysfunction was found in LCS children, with decreased superoxide-producing activity and phagocytosis compared to CG+. The number of complaints of children with LCS correlated significantly with altered neutrophil effector functions.

CONCLUSION: Neutrophil dysfunction in children with LCS may be part of the disease pathogenesis or a predisposing factor.

IMPACT: Using online questionnaires validated during in-person medical examinations and including two different control groups, our study compellingly supports and adds to previous clinical observations in the field. Our study provides valuable insights into the prevalence and characteristics of pediatric LCS, highlighting the significant quality of life and functioning impairment compared to control groups. By detecting neutrophilic granulocyte dysfunction in children with LCS, we shed light on a previously overlooked pathophysiological component of the condition. We demonstrate a significant correlation between clinical symptoms and superoxide production, further enhancing our understanding of the underlying mechanisms of pediatric LCS.}, } @article {pmid39592027, year = {2025}, author = {Danieli, MG and Antonelli, E and Gammeri, L and Longhi, E and Cozzi, MF and Palmeri, D and Gangemi, S and Shoenfeld, Y}, title = {Intravenous immunoglobulin as a therapy for autoimmune conditions.}, journal = {Autoimmunity reviews}, volume = {24}, number = {1}, pages = {103710}, doi = {10.1016/j.autrev.2024.103710}, pmid = {39592027}, issn = {1873-0183}, mesh = {Humans ; *Autoimmune Diseases/immunology/therapy ; COVID-19/immunology/therapy ; *Immunoglobulins, Intravenous/therapeutic use ; }, abstract = {Intravenous immunoglobulin (IVIg) is a medical preparation used as replacement therapy for patients with immunodeficiencies. Over time, IVIg's anti-inflammatory and immunomodulatory effects have been recognized, which have led to the approval of this therapy in the treatment of various pathologies, such as Kawasaki disease, immune thrombocytopenia, and Guillain-Barré syndrome. There are numerous studies in the literature regarding the off-label use of IVIg in the treatment of autoimmune diseases (e.g. myositis and vasculitis), and hematological disorders. Since the role of immunoglobulins in fields other than replacement therapy is now consolidated, in this study we carried out a review of the literature to evaluate the main uses of IVIg therapy. We have focused our attention on the treatment of autoimmune, neurological, hematological, dermatological and pediatric diseases. Furthermore, our analysis of the literature also extended to the potential use of IVIg as an adjuvant treatment of long COVID-19. From our analysis, we found consistent data about IVIg's effectiveness in treating numerous clinical conditions. Treatment with IVIg represents a second-line approach or a valid adjuvant to standard therapies capable of positively influencing the clinical course of many pathologies and reducing or avoiding side effects of standard therapies, with a good safety profile.}, } @article {pmid39590834, year = {2024}, author = {Machado, L and Prudente, R and Franco, E and Gatto, M and Mota, G and Pagan, L and Brizola, L and Dos Santos, M and Cunha, T and Sabino-Silva, R and Goulart, L and Martins, M and Santos, P and Maia, L and Albuquerque, A and Ferreira, E and Baldi, B and Okoshi, M and Tanni, S}, title = {Salivary Metabolomics in Patients with Long COVID-19 Infection.}, journal = {Metabolites}, volume = {14}, number = {11}, pages = {}, pmid = {39590834}, issn = {2218-1989}, abstract = {Background: Long COVID-19 has been characterized by the presence of symptoms lasting longer than 4 weeks after the acute infection. The pathophysiology of clinical manifestations still lacks knowledge. Objective: The objective of this paper was to evaluate metabolite abundance in the saliva of long COVID patients 60 days after hospital discharge. Methods: A convenience sample was composed of 30 post-discharge patients with long COVID and seven non-COVID-19 controls. All COVID-19 patients were evaluated by demographic characteristics, spirometry, 6 min walk test (6mWT), Saint George Respiratory Questionnaire (SGRQ), and body composition. Metabolomics was performed on saliva. Results: The long COVID-19 patients were 60.4 ± 14.3 years-old, and 66% male. Their lean body mass was 30.7 ± 7.3 kg and fat mass, 34.4 ± 13.7 kg. Spirometry evaluation showed forced vital capacity (FVC) of 3.84 ± 0.97 L with 96.0 ± 14.0% of the predicted value, and forced expiratory volume in the first second (FEV1) of 3.11 ± 0.83 L with 98.0 ± 16.0 of the predicted value. The long COVID-19 patients had reduced maximal inspiratory (90.1 ± 31.6 cmH2O) and maximal expiratory (97.3 ± 31.0 cmH2O) pressures. SGRQ showed domain symptoms of 32.3 ± 15.2, domain activities of 41.9 ± 25.6, and domain impact 13.7 ± 11.4, with a mean of 24.3 ± 14.9%. Physical capacity measured by distance covered in the 6mWT was 418.2 ± 130 m with a 73.3% (22.3-98.1) predictive value. The control group consisted of 44.1 ± 10.7-year-old men with a body mass index of 26.5 ± 1.66 Kg/m[2]. Metabolomics revealed 19 differentially expressed metabolites; expression was lower in 16 metabolites, and 2 metabolites were absent in the COVID-19 patients compared to controls. Calenduloside G methyl ester (p = 0.03), Gly Pro Lys (p = 0.0001), and creatine (p = 0.0001) expressions were lower in patients than controls. Conclusions: Long COVID-19 patients present less abundance of calenduloside G methyl ester, Gly Pro Lys, and creatine in saliva than healthy controls. Lower creatine abundance may be related to reduced physical capacity and fatigue.}, } @article {pmid39589967, year = {2024}, author = {Krüger, AL and Haiduk, B and Grau, M}, title = {Identifying Factors That Might Affect Outcomes of Exercise-Based Therapies in Long-COVID.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {39589967}, issn = {2079-9721}, abstract = {BACKGROUND: Long-COVID, which might develop after a SARS-CoV-2 infection, is a rather new disease without standardized treatment strategies. A large number of approaches that integrate physical activity have been described in the literature, and this systematic review aims to examine changes in symptom severity, physical fitness, respiratory symptoms and quality of life during training and identify factors that might influence the respective outcomes.

METHODS: A literature search was conducted using the databases Pubmed, PEDro, BioMed Central, EBSCOhost, ProQuest and the ZBSport from 13 February 2024 to 27 February 2024, and 39 studies fulfilled the search criteria.

RESULTS: The analyzed study designs varied regarding the type of intervention (isolated vs. multidisciplinary), duration and intensity of training sessions and overall length of the program. Individualized holistic concepts of physical activity paralleled by additional approaches demonstrated high effectiveness. However, many of the participants continue to suffer from Long-COVID after the intervention.

CONCLUSIONS: Long-COVID treatment should be individualized, multifactorial and not limited in time and should consider each patient's pre-existing conditions and individual course of the disease to provide the best possible support and care.}, } @article {pmid39587352, year = {2024}, author = {Sigal, A and Neher, RA and Lessells, RJ}, title = {The consequences of SARS-CoV-2 within-host persistence.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {39587352}, issn = {1740-1534}, abstract = {SARS-CoV-2 causes an acute respiratory tract infection that resolves in most people in less than a month. Yet some people with severely weakened immune systems fail to clear the virus, leading to persistent infections with high viral titres in the respiratory tract. In a subset of cases, persistent SARS-CoV-2 replication results in an accelerated accumulation of adaptive mutations that confer escape from neutralizing antibodies and enhance cellular infection. This may lead to the evolution of extensively mutated SARS-CoV-2 variants and introduce an element of chance into the timing of variant evolution, as variant formation may depend on evolution in a single person. Whether long COVID is also caused by persistence of replicating SARS-CoV-2 is controversial. One line of evidence is detection of SARS-CoV-2 RNA and proteins in different body compartments long after SARS-CoV-2 infection has cleared from the upper respiratory tract. However, thus far, no replication competent virus has been cultured from individuals with long COVID who are immunocompetent. In this Review, we consider mechanisms of viral persistence, intra-host evolution in persistent infections, the connection of persistent infections with SARS-CoV-2 variants and the possible role of SARS-CoV-2 persistence in long COVID. Understanding persistent infections may therefore resolve much of what is still unclear in COVID-19 pathophysiology, with possible implications for other emerging viruses.}, } @article {pmid39585134, year = {2024}, author = {Moratalla-Cebrian, ML and Marcilla-Toribio, I and Berlanga-Macias, C and Perez-Moreno, A and Garcia-Martinez, M and Martinez-Andres, M}, title = {Perceptions of Long COVID Patients Regarding Health Assistance: Insights from a Qualitative Study in Spain.}, journal = {Nursing reports (Pavia, Italy)}, volume = {14}, number = {4}, pages = {3361-3377}, pmid = {39585134}, issn = {2039-4403}, abstract = {OBJECTIVE: This study investigates the perceptions of Long COVID patients in Spain regarding the healthcare they receive to identify demands and areas for improvement.

METHODS: Using a qualitative descriptive phenomenological approach, the study included 27 participants selected through non-probabilistic convenience sampling. Data were collected via online semi-structured interviews and analyzed using thematic analysis.

RESULTS: The findings reveal three key themes: (i) health status and challenges in healthcare during the initial COVID-19 infection; (ii) perceptions about healthcare as Long COVID patients; and (iii) demand for and aspects of improving quality of healthcare. The participants, predominantly women (66.67%) with a median age of 51 years, experienced symptoms that they generally perceived as severe, although only 14.81% required hospitalization. The participants reported initial self-management of symptoms at home, which was influenced by familial responsibilities and hospital overcrowding, and the persistence of a wide range of Long COVID symptoms that significantly impacted their daily lives. Satisfaction with healthcare services varied, with frustrations over systemic inefficiencies and long waiting times.

CONCLUSIONS: The study highlights the need for timely access to medical care, comprehensive and empathetic healthcare services, and specialized Long COVID units. The results emphasize the importance of patient-centered approaches and multidisciplinary care to address the complex nature of Long COVID effectively. These findings provide crucial insights for improving healthcare protocols and systems to better support Long COVID patients. This study was prospectively registered with the Ethics Committee for Research on Medicines of the Albacete Integrated Health Care Management System (registry) on 22 February 2022 with registration number 2022/001.}, } @article {pmid39582104, year = {2024}, author = {Zhao, H and Zhang, S and Ma, W}, title = {Agenda Setting in Outpatient Consultation of Older Adults With Long-COVID.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {6}, pages = {e70101}, pmid = {39582104}, issn = {1369-7625}, support = {//This study was supported by the Project of the National Social Science Fund of China 21BYY020, the Key Project of the National Social Science Fund of China 22AZD155, Humanities and Social Sciences Youth Foundation, Ministry of Education of the People's, Republic of China 22YJC740100, and the Project of China Disabled Persons' Federation 2022CDPFHS-18./ ; }, mesh = {Humans ; *COVID-19 ; Aged ; Female ; Male ; *Physician-Patient Relations ; Referral and Consultation ; Aged, 80 and over ; Communication ; Outpatients ; SARS-CoV-2 ; Qualitative Research ; Middle Aged ; }, abstract = {INTRODUCTION: Agenda setting in doctor-patient interaction refers to the process when various agendas are presented and responded to. This study revealed how Long-COVID (LC) agenda items are managed by older adults and doctors during outpatient consultations.

METHODS: Based on audio recordings, we adopted Conversation Analysis (CA) to unveil under what circumstances the patient or the doctor set the agenda and how they collaboratively work to develop an LC topic. Data was transcribed in accordance with the transcription conventions developed by Jefferson.

RESULTS: Agendas were divided into three categories, namely primary, additional, and unmet agenda items. LC agendas were identified with specific characteristics based on qualitative analysis and older adults tended to seek more medical assistance, particularly concerning their chronic diseases. We observed that patients initiate agendas more often than doctors and it could happen at any stage of the visit, both parties can resist expanding the agenda, mostly in an indirect way, and agendas that contain more information with simpler turn-constructions are more likely to be well-addressed.

CONCLUSIONS: Better quality of consultation was found when doctors sensitively detect the emotional change and the potential issues of the patients when they prevaricate to avoid the relevance of the previous infection. The findings also suggested that understanding the dynamics of agenda setting in consultations could lead to improvements in medical visit outcomes.

Patients and doctors in the study were colleagues in a university hospital. They were involved in various stages of this study to ensure it addresses real-world concerns and improves healthcare outcomes. Throughout data collection, patients contributed by allowing their consultations to be recorded and providing feedback on their experiences. Findings were discussed with a patient advisory group to ensure the interpretations aligned with patient perspectives. Doctors were also actively engaged in disseminating the results through later consultations, ensuring broad accessibility and practical application of the research outcomes.}, } @article {pmid39581785, year = {2024}, author = {Mozaffaripour, A and Matheson, AM and Rahman, O and Sharma, M and Kooner, HK and McIntosh, MJ and Rayment, J and Eddy, RL and Svenningsen, S and Parraga, G}, title = {Pulmonary [129]Xe MRI: CNN Registration and Segmentation to Generate Ventilation Defect Percent with Multi-center Validation.}, journal = {Academic radiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.acra.2024.10.029}, pmid = {39581785}, issn = {1878-4046}, abstract = {RATIONALE AND OBJECTIVES: Hyperpolarized [129]Xe MRI quantifies ventilation-defect-percent (VDP), the ratio of [129]Xe signal-void to the anatomic [1]H MRI thoracic-cavity-volume. VDP is associated with airway inflammation and disease control and serves as a treatable trait in therapy studies. Semi-automated VDP pipelines require time-intensive observer interactions. Current convolutional neural network (CNN) approaches for quantifying VDP lack external validation, which limits multicenter utilization. Our objective was to develop an automated and externally validated deep-learning pipeline to quantify pulmonary [129]Xe MRI VDP.

MATERIALS AND METHODS: [1]H and [129]Xe MRI data from the primary site (Site1) were used to train and test a CNN segmentation and registration pipeline, while two independent sites (Site2 and Site3) provided external validation. Semi-automated and CNN-based registration error was measured using mean-absolute-error (MAE) while segmentation error was measured using generalized-Dice-similarity coefficient (gDSC). CNN and semi-automated VDP were compared using linear regression and Bland-Altman analysis.

RESULTS: Training/testing used data from 205 participants (healthy volunteers, asthma, COPD, long-COVID; mean age=54 ± 16y; 119 females) from Site1. External validation used data from 71 participants. CNN and semi-automated [1]H and [129]Xe registrations agreed (MAE=0.3°, R[2] =0.95 rotation; 1.1%, R[2] =0.79 scaling; 0.2/0.5px, R[2] =0.96/0.95, x/y-translation; all p < .001). Thoracic-cavity and ventilation segmentations were also spatially corresponding (gDSC=0.92 and 0.88, respectively). CNN VDP correlated with semi-automated VDP (Site1 R[2]/ρ = .97/.95, bias=-0.5%; Site2 R[2]/ρ = .85/.93, bias=-0.9%; Site3 R[2]/ρ = .95/.89, bias=-0.8%, all p < .001).

CONCLUSION: An externally validated CNN registration/segmentation model demonstrated strong agreement with low error compared to the semi-automated method. CNN and semi-automated registrations, thoracic-cavity-volume and ventilation-volume segmentations were highly correlated with high gDSC for the datasets.}, } @article {pmid39580703, year = {2024}, author = {Scoullar, MJ and Khoury, G and Majumdar, SS and Tippett, E and Crabb, BS}, title = {Towards a cure for long COVID: the strengthening case for persistently replicating SARS-CoV-2 as a driver of post-acute sequelae of COVID-19.}, journal = {The Medical journal of Australia}, volume = {221}, number = {11}, pages = {587-590}, pmid = {39580703}, issn = {1326-5377}, } @article {pmid39580341, year = {2025}, author = {Salvato, M and Doria, A and Giollo, A}, title = {The overlooked epidemic: Fibromyalgia in the shadows of long COVID.}, journal = {Seminars in arthritis and rheumatism}, volume = {70}, number = {}, pages = {152596}, doi = {10.1016/j.semarthrit.2024.152596}, pmid = {39580341}, issn = {1532-866X}, } @article {pmid39580033, year = {2024}, author = {Chow, NKN and Tsang, CYW and Chan, YH and Telaga, SA and Ng, LYA and Chung, CM and Yip, YM and Cheung, PP}, title = {The effect of pre-COVID and post-COVID vaccination on long COVID: A systematic review and meta-analysis.}, journal = {The Journal of infection}, volume = {89}, number = {6}, pages = {106358}, doi = {10.1016/j.jinf.2024.106358}, pmid = {39580033}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/complications/immunology/prevention & control ; *COVID-19 Vaccines/administration & dosage ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention & control/virology ; Quality of Life ; SARS-CoV-2/immunology ; *Vaccination/statistics & numerical data ; }, abstract = {BACKGROUND: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO's definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID.

METHODS: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence.

FINDINGS: We included data from 25 observational studies (n = 14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066).

INTERPRETATION: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID.}, } @article {pmid39579089, year = {2024}, author = {Walters, KM and Clark, M and Dard, S and Hong, SS and Kelly, E and Kostka, K and Lee, AM and Miller, RT and Morris, M and Palchuk, MB and Pfaff, ER}, title = {National COVID Cohort Collaborative Data Enhancements: A Path for Expanding Common Data Models.}, journal = {Journal of the American Medical Informatics Association : JAMIA}, volume = {}, number = {}, pages = {}, doi = {10.1093/jamia/ocae299}, pmid = {39579089}, issn = {1527-974X}, abstract = {INTRODUCTION: To support long COVID research in National COVID Cohort Collaborative (N3C), the N3C Phenotype and Data Acquisition team created data designs to aid contributing sites in enhancing their data. Enhancements include: long COVID specialty clinic indicator; Admission, Discharge, and Transfer (ADT) transactions; patient-level social determinants of health; and in-hospital use of oxygen supplementation.

METHODS: For each enhancement, we defined the scope and wrote guidance on how to prepare and populate the data in a standardized way.

RESULTS: As of June 2024, 29 sites have added at least one data enhancement to their N3C pipeline.

DISCUSSION: The use of common data models is critical to the success of N3C; however, these data models cannot account for all needs. Project-driven data enhancement is required. This should be done in a standardized way in alignment with CDM specifications. Our approach offers a useful pathway for enhancing data to improve fit for purpose.}, } @article {pmid39578604, year = {2024}, author = {Zeuzem, A and Kumar, SD and Oltmanns, C and Witte, M and Mischke, J and Drick, N and Fuge, J and Pink, I and Tauwaldt, J and Debarry, J and Illig, T and Wedemeyer, H and Maasoumy, B and Li, Y and Kraft, ARM and Cornberg, M}, title = {Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29013}, pmid = {39578604}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/immunology/blood/virology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; *Inflammation Mediators/blood/metabolism ; Cross-Sectional Studies ; Hepatitis C/immunology/blood/virology ; Hepatitis C, Chronic/immunology/blood/virology ; Hepacivirus ; Aged ; }, abstract = {Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3-9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection.}, } @article {pmid39576781, year = {2024}, author = {Lee, YS and Kim, H and Kwon, S and Kim, TH}, title = {Association between long COVID and nonsteroidal anti-inflammatory drug use by patients with acute-phase COVID-19: A nationwide Korea National Health Insurance Service cohort study.}, journal = {PloS one}, volume = {19}, number = {11}, pages = {e0312530}, pmid = {39576781}, issn = {1932-6203}, mesh = {Humans ; *Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; *COVID-19/epidemiology ; Republic of Korea/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Case-Control Studies ; Adult ; SARS-CoV-2 ; National Health Programs/statistics & numerical data ; Cohort Studies ; }, abstract = {INTRODUCTION: Long coronavirus disease (COVID) poses a significant burden following the coronavirus disease 2019 (COVID-19) pandemic. Debate persists regarding the impact of nonsteroidal anti-inflammatory drug (NSAID) administration during acute-phase COVID-19 on the development of long COVID. Hence, this study aimed to assess the potential association between NSAID use and long COVID using data from patients with COVID-19 in Korea's National Health Insurance Service.

METHODS: This nested case-control study defined the study cohort as patients diagnosed with COVID-19 for the first time between 2020 and 2021. The primary exposure investigated was NSAID prescriptions within 14 days of the initial COVID-19 diagnosis. We used propensity score matching to create three control patients matched to each patient in the NSAID exposure group. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after the adjustment for demographics, Charlson Comorbidity Index, and existing comorbidities.

RESULTS: Among the 225,458 patients diagnosed with COVID-19, we analyzed data from 254 with long COVID. The adjusted OR (aOR) for NSAID exposure during acute-phase COVID-19 was higher in long COVID cases versus controls (aOR, 1.79; 95% CI, 1.00-3.19), suggesting a potential relationship. However, a sensitivity analysis revealed that the increased odds of NSAID exposure in the acute phase became statistically non-significant (aOR, 1.64; 95% CI, 0.90-2.99) when COVID-19 self-quarantine duration was included as a covariate. Additionally, acetaminophen exposure was not significantly associated (aOR, 1.12; 95% CI, 0.75-1.68), while antiviral drugs demonstrated a stronger association (aOR, 3.75; 95% CI, 1.66-8.48).

CONCLUSION: Although this study suggests a possible link between NSAID use in the acute COVID-19 infection stage and a higher risk of long COVID as well as both NSAID and acetaminophen use during the chronic COVID-19 period and a lower risk of long COVID, the association was not statistically significant. Further research is needed to determine the causal relationship between the various treatment options for acute COVID-19 and the development of long COVID.}, } @article {pmid39576127, year = {2024}, author = {Anshori, I and Marcius, D and Syaifie, PH and Siregar, KAAK and Syakuran, LA and Jauhar, MM and Arda, AG and Shalannanda, W and Mardliyati, E}, title = {Therapeutic Potential of Propolis Extract in Managing Hyperinflammation and Long COVID-19: A Bioinformatics Study.}, journal = {Chemistry & biodiversity}, volume = {}, number = {}, pages = {e202401947}, doi = {10.1002/cbdv.202401947}, pmid = {39576127}, issn = {1612-1880}, support = {//The authors express their gratitude for the financial grants provided by the Bandung Institute of Technology. Additionally, the authors extend our thanks to the Nano Center Indonesia for their support in conducting the research./ ; }, abstract = {Hyperinflammation is a significant factor in long COVID, impacting over 65 million post-COVID-19 individuals globally. Herbal remedies, including propolis, show promise in reducing severity and pro-inflammatory cytokines. However, the natural pharmacological role of propolis in COVID-19 management remains underexplored. Employing network pharmacology and in silico techniques, we assessed propolis extract's potential in countering SARS-CoV-2-induced inflammation. We identified 80 flavonoids via LC-MS/MS QTOF and employed 11 anti-inflammatory drugs as references for inflammation target fishing. Utilizing in silico techniques encompassing target fishing, molecular docking, and dynamics, we examined propolis' effects. We identified 1105 gene targets connected to inflammation through multiple validated target predictors. By integrating SARS-CoV-2 DEGs from GSE147507 with these targets, we identify 25 inflammation-COVID-19-associated propolis targets, including STAT1, NOS2, CFB, EIF2K2, NPY5R, and BTK. Enrichment analyses highlighted primary pharmacological pathways related to Epstein-Barr virus infection and COVID-19. Molecular docking validated isokaempferide, iristectorigenin B, 3'-methoxypuerarin, cosmosiin, and baicalein-7-O-β-d-glucopyranoside, which exhibited strong binding affinity and stability with relevant genes. Moreover, our findings indicate that propolis ligands could potentially suppress reactivation of Epstein-Barr Virus infections in post-COVID-19 cases. However, this study has a limitation in that the concentration of each propolis compound has not been quantified. Therefore, further exploration of propolis compounds quantification and experimental validation are needed to support these findings.}, } @article {pmid39575994, year = {2024}, author = {Somerton, A and Jeffrey, H}, title = {'It's that camaraderie': Experiences of a Long-COVID peer support group for staff working in health, social care and emergency services.}, journal = {Journal of health psychology}, volume = {}, number = {}, pages = {13591053241296184}, doi = {10.1177/13591053241296184}, pmid = {39575994}, issn = {1461-7277}, abstract = {Health, social care and emergency services staff, continue to feel the impact of Long-COVID. Using quantitative and qualitative methods, this study aims to evaluate the experience of UK health and social care staff who participated in a virtual Long-COVID peer support group between May 2021 and May 2023. The outcome measures (SWEMWBS and PHQ9) show an improvement in post-group scores, suggesting participation in the peer support group is linked to improved wellbeing. Thematic analysis identified five key themes: finding connectedness, reciprocity, effective facilitation, filling the gaps and virtual format. This evaluation shows how peer support groups provided space for reciprocity and the positive outcomes associated with this. This evaluation highlights the importance of co-produced, needs-based services providing Long-COVID peer support.}, } @article {pmid39575583, year = {2024}, author = {Choudhury, NA and Mukherjee, S and Singer, T and Venkatesh, A and Perez Giraldo, GS and Jimenez, M and Miller, J and Lopez, M and Hanson, BA and Bawa, AP and Batra, A and Liotta, EM and Koralnik, IJ}, title = {Neurologic Manifestations of Long COVID Disproportionately Affect Young and Middle-Age Adults.}, journal = {Annals of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ana.27128}, pmid = {39575583}, issn = {1531-8249}, support = {K23 AG078705/AG/NIA NIH HHS/United States ; R21 AG086751/AG/NIA NIH HHS/United States ; K23AG078705 to EML//NIH/NIA/ ; R21AG086751 to AB//NIH/NIA/ ; }, abstract = {OBJECTIVE: To investigate neurologic manifestations of post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients across the adult lifespan.

METHODS: Cross-sectional study of the first consecutive 200 PNP and 1,100 NNP patients evaluated at a Neuro-coronavirus disease 2019 (COVID-19) clinic between May 2020 and March 2023. Patients were divided into younger (18-44 years), middle-age (45-64 years), and older (65+ years) age groups.

RESULTS: Younger and middle-age individuals accounted for 142 of 200 (71%) of PNP and 995 of 1100 (90.5%) of NNP patients. Significant age-related differences in the frequencies of comorbidities and abnormal neurologic findings demonstrated higher prevalence in older patients. Conversely, 10 months from COVID-19 onset, we found significant age-related differences in Neuro-PASC symptoms indicating lower prevalence, and therefore, symptom burden, in older individuals. Moreover, there were significant age-related differences in subjective impression of fatigue (median [interquartile range (IQR)] patient-reported outcomes measurement information system [PROMIS] score: younger 64 [57-69], middle-age 63 [57-68], older 60.5 [50.8-68.3]; p = 0.04) and sleep disturbance (median [IQR] PROMIS score: younger 57 [51-63], middle-age 56 [53-63], older 54 [46.8-58]; p = 0.002) in the NNP group, commensurate with higher impairment in quality of life (QoL) among younger patients. Finally, there were significant age-related differences in objective executive function (median [IQR] National Institutes of Health [NIH] toolbox score: younger 48 [35-63], middle-age 49 [38-63], older 54.5 [45-66.3]; p = 0.01), and working memory (median [IQR] NIH toolbox score: younger 47 [40-53], middle-age 50 [44-57], older 48 [43-58]; p = 0.0002) in NNP patients, with the worst performance coming from the younger group.

INTERPRETATION: Younger and middle-age individuals are disproportionally affected by Neuro-PASC regardless of acute COVID-19 severity. Although older people more frequently have abnormal neurologic findings and comorbidities, younger and middle-age patients suffer from a higher burden of Neuro-PASC symptoms and cognitive dysfunction contributing to decreased QoL. Neuro-PASC principally affects adults in their prime, contributing to profound public health and socioeconomic impacts warranting dedicated resources for prevention, diagnosis and interventions. ANN NEUROL 2024.}, } @article {pmid39575513, year = {2024}, author = {Ramírez-Vélez, R and Oteiza, J and Legarra-Gorgoñon, G and Oscoz-Ochandorena, S and García-Alonso, N and García-Alonso, Y and Correa-Rodríguez, M and Soto-Mota, A and Izquierdo, M}, title = {Exercise training in long COVID: the EXER-COVID trial.}, journal = {European heart journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurheartj/ehae721}, pmid = {39575513}, issn = {1522-9645}, support = {PID2020-113098RB-I00//Proyectos de I+D+i/ ; }, } @article {pmid39574837, year = {2024}, author = {Kanu, JS and Vandi, MA and Bangura, B and Draper, K and Gorina, Y and Foster, MA and Harding, JD and Ikoona, EN and Jambai, A and Kamara, MAM and Kaitibi, D and Moffett, DB and Singh, T and Redd, JT}, title = {Promoting Awareness of Data Confidentiality and Security During the COVID-19 Pandemic in a Low-Income Country-Sierra Leone.}, journal = {Public health reviews}, volume = {45}, number = {}, pages = {1607540}, pmid = {39574837}, issn = {0301-0422}, abstract = {OBJECTIVES: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders.

METHODS: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge.

RESULTS: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders.

CONCLUSION: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited.}, } @article {pmid39574217, year = {2024}, author = {Xia, S and Liang, E and Xu, L and Tan, L and Guo, X and Cheng, K}, title = {Ultrasensitive Chemiluminescence Probes Designed from Covalent Inhibitors for SRAS-CoV-2 M[pro] Detection.}, journal = {Analytical chemistry}, volume = {96}, number = {49}, pages = {19641-19650}, doi = {10.1021/acs.analchem.4c04774}, pmid = {39574217}, issn = {1520-6882}, mesh = {*SARS-CoV-2/isolation & purification/enzymology/drug effects ; Humans ; *Luminescent Measurements/methods ; Coronavirus 3C Proteases/antagonists & inhibitors/metabolism ; Limit of Detection ; COVID-19/virology/diagnosis ; Protease Inhibitors/pharmacology/chemistry/analysis ; Animals ; }, abstract = {In the postpandemic era, the emergence of "long COVID" from SARS-CoV-2 has brought ongoing negative impacts on individual health and society. The development of more efficient methods for drug screening and monitoring viral activity remains a critical need. The main protease (M[pro]), due to its important role in the virus lifecycle, high conservation, and specificity, is considered an ideal biomarker for SARS-CoV-2. Herein, we have developed several chemiluminescence probes based on different substrates modified from covalent inhibitors targeted at M[pro]. Among these, the best probe, MPCL-2, exhibits a rapid response (<20 min), an extremely low limit of detection (LoD; 0.11 nM), great selectivity, and chemical stability. After validating the probe's mechanism of action, MPCL-2 can also be used for real-time, in-situ imaging of enzymes in cells infected with the authentic virus and has the potential for real-time, in-situ M[pro] imaging in vivo. Compared to other methods reported to date, the probe demonstrates superior performance and broader applicability, such as in drug screening or virus activity monitoring. Further, the unique design strategy for the substrate can be adopted to develop sensitive probes for other pathogens.}, } @article {pmid39572348, year = {2024}, author = {Wolfschmidt, A and Ott, S and Richter, S and Schmidt, J and Uter, W and Drexler, H and Finkenzeller, T}, title = {[Long-/Post-COVID symptoms in a hotspot collective of the first wave of the SARS-CoV-2 pandemic in Germany].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {190-191}, number = {}, pages = {13-19}, doi = {10.1016/j.zefq.2024.10.002}, pmid = {39572348}, issn = {2212-0289}, mesh = {Humans ; *COVID-19/epidemiology ; Germany ; Female ; Male ; Adult ; Middle Aged ; *Pandemics ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Aged ; }, abstract = {INTRODUCTION: Despite a high number of long/post-COVID cases and an enormous psychological strain on the part of the patients, no scientific consensus has yet been reached on a clearly defined disease entity. The comprehensive media coverage has made the public more sensitive to this topic, which makes it more difficult to take an objective perspective.

METHODS: We report on long/post-COVID symptoms in a hotspot collective of the first SARS-CoV-2 wave of infections in Germany; these infections began in Spring 2020 and therefore preceded the start of an intensive media coverage. In June/July 2021, 122 employees of the Kliniken Nordoberpfalz AG who tested positive for SARS-CoV-2 during the first wave of the pandemic were asked about their infection and its consequences using a standardised questionnaire.

RESULTS: 82 participants (67 %) complained of persistent symptoms (post-COVID: 29 %). Long/post-COVID symptoms occurred more frequently in those who had experienced symptoms during the acute phase of the infection. Patients with stomach pain as an acute symptom more frequently reported a symptom duration of > 12 weeks. The probability of symptoms persisting > 12 weeks was reduced if throat pain or sniffling had been reported as an acute symptom. Emergence and duration of symptoms were independent of any demographic or occupational factors or of pre-existing conditions.

DISCUSSION: Due to having been infected in a hotspot region during the first wave of the pandemic, the study collective exhibits certain peculiarities which must be considered when interpreting the results. The lack of evidence for many risk factors discussed in the literature, together with the challenges facing scientific studies, seems to suggest a more differentiated approach to dealing with post-COVID.}, } @article {pmid39571342, year = {2024}, author = {Calvani, R and Giampaoli, O and Marini, F and Del Chierico, F and De Rosa, M and Conta, G and Sciubba, F and Tosato, M and Picca, A and Ciciarello, F and Galluzzo, V and Gervasoni, J and Di Mario, C and Santoro, L and Tolusso, B and Spagnoli, M and Tomassini, A and Aureli, W and Toto, F and Pane, S and Putignani, L and Miccheli, A and Marzetti, E and Landi, F and , }, title = {Beetroot juice intake positively influenced gut microbiota and inflammation but failed to improve functional outcomes in adults with long COVID: A pilot randomized controlled trial.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {344-358}, doi = {10.1016/j.clnu.2024.11.023}, pmid = {39571342}, issn = {1532-1983}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; *Beta vulgaris/chemistry ; *Fruit and Vegetable Juices ; Pilot Projects ; Adult ; Double-Blind Method ; Middle Aged ; *COVID-19 ; *Inflammation ; Dietary Supplements ; Nitrates ; SARS-CoV-2 ; Young Adult ; }, abstract = {BACKGROUND & AIMS: Long-term effects of coronavirus disease 2019 (long COVID) develop in a substantial number of people following an acute COVID-19 episode. Red beetroot juice may have positive effects on multiple pathways involved in long COVID. The aim of this pilot study was to explore the impact of beetroot juice supplementation on physical function, gut microbiota, and systemic inflammation in adults with long COVID.

METHODS: A single-center, double-blind, placebo-controlled randomized trial was conducted to test the effects of 14 days of beetroot juice supplementation, rich in nitrates and betalains, on functional and biological outcomes in adults aged between 20 and 60 years with long COVID. Participants were randomized 1:1 to receive either daily oral supplementation with 200 mL beetroot juice (∼600 mg nitrate) or placebo (∼60 mg nitrate) for 14 days. The primary endpoint was the change from baseline to day 14 in a fatigue resistance test. Secondary outcomes included the distance walked on the 6-min walk test, handgrip strength, and flow-mediated dilation. Secondary endpoints also included changes from baseline in circulating inflammatory mediators and metagenomic and fecal water metabolomic profiles. Partial least squares discriminant analysis (PLS-DA) models were built to evaluate the differences in biological variables associated with the interventions.

RESULTS: Thirty-one participants were randomized in the study. Twenty-five of them (median (interquartile range) age 40 (10), 14 [56 %] women), received either beetroot juice (15) or placebo (10) and completed the study. At 14 days, fatigue resistance significantly improved from baseline (mean difference [standard error]: +21.8 [3.7] s; p < 0.001) with no significant differences between intervention groups. A significant increase from baseline in the distance walked on the 6-min walk test was observed (mean difference [standard error]: +30.0 [9.4] m; p = 0.03), which was not different between groups. Flow-mediated dilation did not differ between participants who received beetroot juice and those on placebo. PLS-DA models allowed correct classification of participants with 92.2 ± 4.4 % accuracy. Those who ingested red beetroot juice had a greater abundance of bacteria with well-known beneficial effects, including Akkermansia, Oscillospira, Prevotella, Roseburia, Ruminococcaceae, and Turicibacter, compared with placebo. Participants allocated to beetroot juice supplementation were also characterized by significantly higher levels of fecal nicotinate, trimethylamine, and markers of beetroot juice intake (e.g., 5,6-dihydroxyindole). Finally, higher levels of interferon gamma and macrophage inflammatory protein-1β were found in participants who consumed beetroot juice.

CONCLUSION: Beetroot juice supplementation for two weeks did not to induce significant improvements in functional outcomes in adults with long COVID compared with placebo. Beneficial effects were observed in both gut microbiota composition (i.e., increase in probiotic species) and inflammatory mediators.

TRIAL REGISTRATION: Trial was registered under ClinicalTrials.gov. Identifier no. NCT06535165.}, } @article {pmid39569188, year = {2024}, author = {Dai, R and Peng, W and Xu, N and Qin, P and Ding, L and Hua, Q and Jiang, J and He, F and Zhang, H}, title = {Clinical characteristics and antibody response to Omicron variants among solid carcinoma patients in China on the 2022.12-2023.4 wave of the COVID-19 pandemic.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1476186}, pmid = {39569188}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/virology/epidemiology ; *SARS-CoV-2/immunology ; Male ; Female ; China/epidemiology ; Middle Aged ; *Antibodies, Viral/blood/immunology ; Cross-Sectional Studies ; *Neoplasms/immunology ; Adult ; Aged ; Immunoglobulin G/blood/immunology ; Antibodies, Neutralizing/blood/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Carcinoma/immunology/virology ; Pandemics ; }, abstract = {BACKGROUND: China experienced a surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants after adjusting its zero-coronavirus disease 2019 (COVID-19) policy. Although infections with Omicron variants are generally less severe than infections with previous SARS-CoV-2 variants, the clinical characteristics, persistent symptoms, and antibody responses in solid carcinoma patients (SCPs) with COVID-19 during the Omicron wave are unclear.

METHODS: We conducted a cross-sectional study in April 2023, recruiting healthy controls (HCs) from the community and SCPs from Zhejiang Provincial People's Hospital. Serum samples were collected, and a questionnaire was used to assess SARS-CoV-2 infection status, including demographic characteristics, clinical manifestations, and "long COVID" symptoms. Humoral immune responses were analyzed by enzyme-linked immunosorbent assays (ELISAs) targeting immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD; Omicron BA.4/5) protein and cell culture-based neutralization assays against Omicron variants (BA.4/5, BF.7, XBB.1.5, and EG.5).

RESULTS: In total, 298 SCPs and 258 HCs were enrolled. Self-reported COVID-19 case rates were significantly lower in SCPs than in HCs (78.5% vs. 93.8%, P<0.001). Common COVID-19 symptoms were similar between the two groups, primarily comprising general (92.6% vs. 84.9%) and respiratory symptoms (51.9% vs. 48.2%) after acute infection. There was no significant difference in persistent symptoms at 1-3 months post-infection (P=0.353); fatigue was the most common symptom (45.0% vs. 44.8%). SCPs exhibited lower anti-RBD-IgG titers compared with HCs (1.061 vs. 1.978, P=0.001). The 50% pseudovirus neutralization titer (pVNT50) values for prevalent Omicron strains (BA.4/5 and BF.7) were lower in SCPs than in HCs (621.0 [288.8, 1333.0] vs. 894.1 [458.5, 1637.0] and 529.6 [215.3, 1264.5] vs. 463.1 [185.2, 914.0], respectively). Levels of antibodies against subsequent variants (XBB.1.5 and EG.5) also were reduced. There were no significant differences among carcinoma types in the levels of antibodies against Omicron variants. However, SCPs who received the SARS-CoV-2 vaccine or had COVID-19 during the Omicron wave displayed higher antibody levels.

CONCLUSIONS: This study elucidated the clinical and immunological characteristics of SCPs during the Omicron wave in China after the shift away from a zero-COVID-19 policy. Our findings provide insights regarding factors that influence COVID-19 symptoms and antibody levels in this population.}, } @article {pmid39569098, year = {2024}, author = {Bhargav, H and Raghavan, V and Rao, NP and Gulati, K and Binumon, KV and Anu, KN and Ravi, S and Jasti, N and Holla, B and Varambally, S and Ramachandran, P}, title = {Validation and efficacy of a tele-yoga intervention for improving psychological stress, mental health and sleep difficulties of stressed adults diagnosed with long COVID: a prospective, multi-center, open-label single-arm study.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1436691}, pmid = {39569098}, issn = {1664-1078}, abstract = {The objective of this study was to validate and test the efficacy of a 16-week tele-yoga intervention for perceived stress, anxiety, depression, and insomnia in individuals who had had COVID-19 infection in the previous year, and had reported moderately high levels of psychological stress (PSS ≥14). 25 and 50-min versions of the program were developed. They were then validated using Lawshe's content validity ratio after obtaining feedback from 20 yoga therapy experts. The safety and efficacy of the two programs were subsequently tested in a prospective, multicenter, open-label single-arm study. Eighty-six adults (18 male, 68 female) were recruited from two tertiary mental healthcare institutions, 48 in NIMHANS, Bengaluru; and 38 in SCARF, Chennai. Participants were assessed at weeks zero, 4, and 16 using validated tools. Data were analyzed using a Mixed Model, Intention to Treat approach. After week 16, 31 subjects remained in the trial and continued to practice yoga without any side effects. Subjects who adhered in the trial had significantly higher levels of baseline anxiety and depression as compared to subjects who dropped out. Results at week 4 included significant reductions in levels of perceived stress, anxiety, and insomnia; improvements were maintained at week 16. Correlations between number of yoga sessions and post-intervention PSS scores were negative (r = -0.49), and significant (p< 0.05). Both tele-yoga programs proved safe, useful tools to counteract perceived stress, anxiety and insomnia. Future trials should explore the utility of tele-yoga as a tool to enhance well-being and manage stress.}, } @article {pmid39568467, year = {2024}, author = {Wu, Q and Pajor, NM and Lu, Y and Wolock, CJ and Tong, J and Lorman, V and Johnson, KB and Moore, JH and Forrest, CB and Asch, DA and Chen, Y}, title = {A latent transfer learning method for estimating hospital-specific post-acute healthcare demands following SARS-CoV-2 infection.}, journal = {Patterns (New York, N.Y.)}, volume = {5}, number = {11}, pages = {101079}, pmid = {39568467}, issn = {2666-3899}, abstract = {The long-term complications of COVID-19, known as the post-acute sequelae of SARS-CoV-2 infection (PASC), significantly burden healthcare resources. Quantifying the demand for post-acute healthcare is essential for understanding patients' needs and optimizing the allocation of valuable medical resources for disease management. Driven by this need, we developed a heterogeneous latent transfer learning framework (Latent-TL) to generate critical insights for individual health systems in a distributed research network. Latent-TL enhances learning in a specific health system by borrowing information from all other health systems in the network in a data-driven fashion. By identifying subpopulations with varying healthcare needs, our Latent-TL framework can provide more effective guidance for decision-making. Applying Latent-TL to electronic health record (EHR) data from eight health systems in PEDSnet, a national learning health system in the US, revealed four distinct patient subpopulations with heterogeneous post-acute healthcare demands following COVID-19 infections, varying across subpopulations and hospitals.}, } @article {pmid39562810, year = {2024}, author = {Chaves, ECR and Quaresma, JAS and Rodrigues, MHC and de Menezes, DC and de Lima, IC and de Sousa, JR and Galúcio, VCA and Queiroz, MAF and Brasil-Costa, I and Barros, MC and Ribeiro-Dos-Santos, Â and Vallinoto, ACR and Falcão, LFM and de Lima, PDL}, title = {Altered leukocyte pattern and inflammatory markers in unvaccinated long covid patients: a cross-sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28617}, pmid = {39562810}, issn = {2045-2322}, support = {005/2020//Amazon Research Foundation (FAPESPA)/ ; 006/2020//Amazon Research Foundation (FAPESPA)/ ; #401235/2020-3//The National Council for Scientific and Technological Development/ ; 09/2021//Secretariat for Science, Technology and Higher, Professional and Techno-logical Education/ ; Financial code 001, notice no. 13/2020//Coordination for the Improvement of Higher Education Personnel - Brazil/ ; 406360/2022-7//National Council for Scientific and Technological Development - Brazil/ ; }, mesh = {Humans ; *COVID-19/blood/immunology ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; *Cytokines/blood ; *Biomarkers/blood ; Aged ; *SARS-CoV-2/isolation & purification ; Leukocyte Count ; Leukocytes/metabolism ; Adult ; Inflammation/blood ; Brazil/epidemiology ; Monocytes/immunology ; }, abstract = {Long Covid results from the damage caused by SARS-CoV-2, involving the release of cytokines and the continuous activation of immune cells. This cross-sectional study investigates leukocyte and cytokine profiles in Long Covid patients in the Amazon, a region where such studies are limited. Blood samples were analysed for differential leukocyte counts and cytokine levels. We suggest elevated lymphocyte counts in hospitalised patients and those with severe COVID-19. Higher eosinophil counts were observed in patients with up to three months of Long Covid, and increased monocyte counts in those with up to six months. IL-2 levels were higher in patients with fewer symptoms and Long Covid duration of more than three months, whereas IL-10 may remain elevated for up to 12 months. We suggest positive correlations between neutrophils, monocytes, eosinophils, and lymphocytes with different cytokines (IFN-γ, IL-6, IL-4, IL-17a, IL-2). Women were associated with lower hospitalisation rates and longer durations of Long Covid; increased lymphocyte counts were linked to hospitalisation due to COVID-19, while higher monocyte counts were associated with Long Covid durations of up to six months. We suggest that Long Covid patients may exhibit alterations in inflammatory markers, indicating a persistently pro-inflammatory microenvironment that tends to diminish after 12 months of Long Covid.}, } @article {pmid39560821, year = {2024}, author = {Carosi, G and Cremaschi, A and Giavoli, C and Ferrante, E and Mantovani, G}, title = {Hypopituitarism and COVID-19.}, journal = {Pituitary}, volume = {27}, number = {6}, pages = {925-934}, pmid = {39560821}, issn = {1573-7403}, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Hypopituitarism/etiology ; *SARS-CoV-2 ; Pituitary Gland ; Pandemics ; }, abstract = {PURPOSE: This review aims to collect and examine recent research findings regarding hypopituitarism and COVID-19, focusing on the virus's impact on the pituitary gland and the outcomes for infected patients with hormonal deficiencies.

METHODS: Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Pituitary" and "Hypopituitarism".

RESULTS: Many studies have aimed to evaluate the function of the pituitary gland in infected patients, revealing variable degrees of deficiencies. The results are very heterogenous mostly because many different tests and hormonal cut-off have been adopted. It is unclear whether primary virus damage or the inflammatory response is responsible for these hormonal alterations. Interestingly, pituitary defects may persist long after the initial infection, possibly contributing to the "Long COVID syndrome". However, data on the recovery of pituitary function and long-term follow-up are not yet available. On the other hand, although findings are not consistent, patients with hypopituitarism may be at a higher risk for COVID-19 infection rate, complications, and mortality.

CONCLUSION: The COVID-19 pandemic presented challenges for endocrinologists. The endocrine system appears to be involved in both the acute phase of infection and the recovery period. Hypopituitarism can be a consequence of SARS-COV-2 infection, and patients with existing hypopituitarism may face higher risks of complications. It is advisable to educate these patients on how to adjust their replacement therapies. Long-term follow-up data on pituitary function after recovery from COVID-19 are needed.}, } @article {pmid39560319, year = {2025}, author = {Jalalizadeh, M and Buosi, K and Giacomelli, CF and Leme, PAF and Ferrari, KL and Dionato, FAV and Brito, WRS and Brunetti, NS and Maia, AR and Morari, J and Pagliarone, AC and Farias, AS and Velloso, LA and Queiroz, MAF and Vallinoto, ACR and Bajgelman, MC and Reis, LO}, title = {Therapeutic BCG vaccine protects against long COVID: The BATTLE randomized clinical trial.}, journal = {Journal of internal medicine}, volume = {297}, number = {1}, pages = {60-78}, doi = {10.1111/joim.20033}, pmid = {39560319}, issn = {1365-2796}, support = {88887.506617/2020-00//Coordination for the Improvement of Higher Education Personnel, CAPES, Federal Government, Brazil/ ; 88887.657670/2021-00//Coordination for the Improvement of Higher Education Personnel, CAPES, Federal Government, Brazil/ ; //General Coordination of the National Immunization Program - CGPNI/DEIDT/SVS/MS/ ; 465/2020//Ministry of Health, Brazil/ ; 304747/2018-1//National Council for Scientific and Technological Development-CNPq, Research Productivity/ ; 310135/2022-2//National Council for Scientific and Technological Development-CNPq, Research Productivity/ ; 302935/2021-5//National Council for Scientific and Technological Development-CNPq, Research Productivity/ ; }, mesh = {Humans ; *BCG Vaccine/therapeutic use ; Male ; Female ; *COVID-19/prevention & control/immunology ; Double-Blind Method ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Bacillus Calmette-Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.

OBJECTIVES: To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.

METHODS: Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial.

INTERVENTION: BCG intradermal vaccine and placebo.

PATIENTS: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up.

MEASUREMENTS: Long COVID symptoms and mechanistic analyses.

RESULTS: BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages.

CONCLUSION: Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex.

LIMITATIONS: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months.}, } @article {pmid39559920, year = {2024}, author = {Doehner, W and Fischer, A and Alimi, B and Muhar, J and Springer, J and Altmann, C and Schueller, PO}, title = {Intermittent Hypoxic-Hyperoxic Training During Inpatient Rehabilitation Improves Exercise Capacity and Functional Outcome in Patients With Long Covid: Results of a Controlled Clinical Pilot Trial.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {15}, number = {6}, pages = {2781-2791}, pmid = {39559920}, issn = {2190-6009}, mesh = {Humans ; Female ; *COVID-19/rehabilitation/complications ; Male ; Middle Aged ; Pilot Projects ; *SARS-CoV-2 ; Prospective Studies ; Aged ; Treatment Outcome ; Inpatients ; Quality of Life ; Exercise Tolerance ; Exercise Therapy/methods ; Hypoxia/rehabilitation ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID-19 illness is a severely disabling disease with shortness of breath, weakness and fatigue as leading symptoms, resulting in poor quality of life and substantial delay in return to work. No specific respiratory therapy has been validated for patients with long COVID. The intermittent hypoxia-hyperoxia training (IHHT) is a respiratory therapeutic modality to improve exercise performance via controlled respiratory conditioning. The purpose of the present study is to investigate the therapeutic effect of IHHT on functional and symptomatic recovery of patients with long COVID syndrome.

METHODS: A prospective, controlled, open-treatment interventional study was conducted in patients with long COVID who were admitted to an inpatient rehabilitation programme. Patients were assigned nonrandomized to receive IHHT in addition to the standardized rehabilitation programme (IHHT group) or standard rehabilitation alone (control group). The IHHT group received supervised sessions of intermittent hypoxic (10-12% O2) and hyperoxic (30-35% O2) breathing three times per week throughout the rehabilitation period. Primary endpoint was improved walking distance in a 6-min walk test (6MWT) between study groups. Secondary endpoints were change in stair climbing power, dyspnoea (Borg dyspnoea Scale), fatigue assessment scale (FAS) and change in health-related quality of life (HRQoL) assessed by patient global assessment (PGA), EQ-5D analogue scale and the MEDIAN Corona Recovery Score (MCRS). Further assessments included maximum handgrip strength, nine hole peg test, timed up-and-go, respiratory function and functional ambulation category (FAC), serum analyses and safety of the intervention.

RESULTS: A total of 145 patients were included in the study (74% female, mean age 53 ± 12 years) and assigned to IHHT (n = 70) or standard care (n = 75). The 6MWT distance improved 2.8-fold in the IHHT group compared to the control group (91.7 ± 50.1 m vs. 32.6 ± 54.2 m, ANCOVA p < 0.001). Stair climbing power improved 3.7-fold in the IHHT group compared to controls (-1.91 ± 2.23 s vs. -0.51 ± 1.93 s, p < 0.001). Secondary endpoints on dyspnoea, fatigue and HRQoL (PGA, EQ-5D and MCRS) improved significantly in the IHHT group compared to controls. The IHHT group exhibited a significant decrease in blood pressure, heart rate and increase in haemoglobin levels that was not observed in the control group. No adverse events were observed.

CONCLUSION: Respiratory treatment with IHHT in addition to a multidisciplinary rehabilitation programme improves functional capacity, symptomatic status and quality of life in patients with disabling long COVID. IHHT has been demonstrated to be safe, well tolerated and feasible to be integrated in an inpatient rehabilitation programme to improve outcome in long COVID.}, } @article {pmid39559556, year = {2024}, author = {Chen, YH and Hsieh, YS}, title = {A Narrative Review of Impact of Incentive Spirometer Respiratory Training in Long COVID.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {5233-5246}, pmid = {39559556}, issn = {1178-7074}, abstract = {Long COVID refers to symptoms that appear 3 months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of Coronavirus disease 2019 (COVID-19), and last for at least 2 months, not attributable to other diagnoses. This health issue significantly burdens patients' quality of life, the economy, and society. Improving the af-termath of COVID-19 is a crucial global health issue in the post-pandemic era. According to current results, it is evident that developing a simple, low-cost respiratory training method that can be easily used at home by themselves with long Coronavirus disease 2019 symptoms (long COVID) is an important and urgent issue. The incentive spirometer is widely used in physical, speech, and respiratory therapy, as well as in preventing postoperative pulmonary infections and improving sputum clearance. However, to date, the role of incentive spirometer respiratory training in long COVID symptoms is still limited. In this literature review is presented to explore the effectiveness of incentive spirometer respiratory training in alleviating symptoms among individuals recovering from long COVID. We also compile non-invasive assessment methods, with the aim to enable individuals to undergo training and assessments conveniently at home or in the community. In this review, a literature review approach was utilized to explore the effectiveness of incentive spirometer intervention in alleviating long-term COVID symptoms. This study is to synthesize the findings of articles published during January 2019 and December 2023 retrieved from PubMed/CINAHL/MEDLINE/ Google Scholar without re-strictions on study type. We ultimately identified seven articles and have summarized similar past studies. This review could contribute to improving symptoms related to long COVID by incentive spirometer respiratory training and serve as practical reference material for clinical medical staff and provide insights for healthcare policymakers in de-veloping guidelines for future research directions, clinical guidance, and educational strategies in the context of nursing care.}, } @article {pmid39558820, year = {2024}, author = {de Miguel-Perez, D and Arroyo-Hernandez, M and La Salvia, S and Gunasekaran, M and Pickering, EM and Avila, S and Gebru, E and Becerril-Vargas, E and Monraz-Perez, S and Saharia, K and Grazioli, A and McCurdy, MT and Frieman, M and Miorin, L and Russo, A and Cardona, AF and García-Sastre, A and Kaushal, S and Hirsch, FR and Atanackovic, D and Sahoo, S and Arrieta, O and Rolfo, C}, title = {Extracellular vesicles containing SARS-CoV-2 proteins are associated with multi-organ dysfunction and worse outcomes in patients with severe COVID-19.}, journal = {Journal of extracellular vesicles}, volume = {13}, number = {11}, pages = {e70001}, pmid = {39558820}, issn = {2001-3078}, support = {U54CA260560//NCI-SERONET/ ; CEIRR//NIAID-funded Center of Excellence for Influenza Research and Response/ ; 75N93021C00014/AI/NIAID NIH HHS/United States ; R01 DK125856/DK/NIDDK NIH HHS/United States ; R01HL140469//NIH-NHLBI/ ; R01HL148786//NIH-NHLBI/ ; U19AI135972/AI/NIAID NIH HHS/United States ; U19AI168631/AI/NIAID NIH HHS/United States ; //Evox Therapeutics, UK/ ; //CRIPT (Center for Research on Influenza Pathogenesis and Transmission)/ ; }, mesh = {Humans ; *COVID-19/complications/blood/metabolism ; *Extracellular Vesicles/metabolism ; *SARS-CoV-2 ; Female ; Male ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Aged ; *Multiple Organ Failure/etiology/blood ; Biomarkers/blood ; Spike Glycoprotein, Coronavirus/metabolism ; Interleukin-6/blood/metabolism ; Coronavirus Nucleocapsid Proteins/metabolism ; Severity of Illness Index ; Phosphoproteins/metabolism/blood ; COVID-19 Drug Treatment ; Adult ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL-6 with severe cases led to the early evaluation of the anti-IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID-19 sequelae, and biomarkers are needed to understand and anticipate these processes. Because extracellular vesicles (EVs) play an important role in viral infection and immune response, they could potentially serve as predictive and prognostic biomarkers. We isolated EVs from 39 patients with severe COVID-19, from which 29 received tocilizumab and 10 were considered controls. Blood samples, which were collected at hospitalisation before treatment, at Day 7, and Day 15 during follow-up, were assessed by immunoblot for longitudinal expression of spike (S) and nucleocapsid (N) proteins. Dynamic expression was calculated and compared with clinicopathological and experimental variables. Expression of EV S was validated by immunogold and imaging flow-cytometry, revealing an enrichment in CD9+ EVs. As a result, decreasing expression of EV viral proteins was observed in patients treated with tocilizumab. Moreover, higher increase in EV S was observed in patients with lower antibody response, hyperfibrinogenemia, lower respiratory function, higher blood pressure and shorter outcomes. These findings lay the foundation for future studies characterizing the role of EVs in multiorgan assessment and identifying biomarkers in patients with severe COVID-19 and possible long COVID.}, } @article {pmid39558292, year = {2024}, author = {Gennaro, FD and Veronese, N and Segala, FV and Frallonardo, L and Guido, G and Cormio, M and Romita, G and Parisi, A and Marrone, E and Ciuppa, ME and Carrubba, A and Carruba, L and Licata, A and Cavallaro, G and Pagliuso, V and Maino, T and Lollo, S and Latino, L and Solimeo, LT and Ianniello, A and Montalbò, D and Bavaro, DF and Fiorella, ML and Barbagallo, M and Saracino, A}, title = {Protective role of vaccination on the development of long COVID: data from a large, multicenter, prospective cohort study.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1313}, pmid = {39558292}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Italy/epidemiology ; *SARS-CoV-2/immunology ; Incidence ; Risk Factors ; Vaccination/statistics & numerical data ; COVID-19 Vaccines/administration & dosage ; Post-Acute COVID-19 Syndrome ; Adult ; Hospitalization/statistics & numerical data ; }, abstract = {BACKGROUND: Long COVID, a highly heterogeneous syndrome affecting millions of people worldwide, is emerging as an urgent public health threat, but data on the predictors of specific clinical manifestations over long follow-up periods are limited. The aim of this study is to investigate the role of viral variants and other predictors in long COVID incidence and clinical manifestations.

METHODS: All COVID-19 patients aged > 18 years and hospitalized from March 1 2020 to April 2022 in two Italian University Hospitals were enrolled. Incidence and clinical presentation of long COVID were assessed through structured questionnaires delivered by phone calls. The association between possible risk factors collected during hospitalization and long COVID was reported using an adjusted logistic regression and reported as odds ratios (ORs) with their 95% confidence intervals (CIs).

RESULTS: Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Overall, 54% reported long COVID symptomatology between 18 and 24 months. Multivariate analysis suggested that being vaccinated against SARS-CoV-2 was associated with reduced odds of reporting any long COVID symptomatology (OR: 0.34; 95% CI: 0.21-0.58), while infection with the Delta variant was a strong predictor (OR: 9.61, p < 0.0001) for the development of post-COVID conditions characterized by neuropsychiatric symptoms.

CONCLUSIONS: In this study long COVID symptoms were still highly prevalent after 18-24 months of follow-up and, when compared to wild-type virus, infection with the Delta variant was associated with a higher risk of developing a neurological post-COVID condition.}, } @article {pmid39558250, year = {2024}, author = {Cataldo, SA and Micciulli, A and Margulis, L and Cibeyra, M and Defeo, S and Horovitz, SG and Martino, A and Melano, R and Mena, M and Parisi, F and Santoro, D and Sarmiento, F and Belzunce, MA}, title = {Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina.}, journal = {BMC neurology}, volume = {24}, number = {1}, pages = {450}, pmid = {39558250}, issn = {1471-2377}, support = {FITBA-B06//Ministerio de Producción, Ciencia e Innovación Tecnológica de la Provincia de Buenos Aires, Argentina/ ; PICT-PRH-2022-01//Agencia Nacional de Promoción Científica y Tecnológica, Argentina/ ; }, mesh = {Humans ; Argentina/epidemiology ; *COVID-19/complications/diagnostic imaging/psychology/pathology ; Cross-Sectional Studies ; Male ; Female ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Brain/diagnostic imaging/pathology/virology ; *Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/etiology/diagnostic imaging/pathology ; Cohort Studies ; Aged ; Adult ; Cognition/physiology ; }, abstract = {OBJECTIVE: Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina.

METHODS: We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons.

RESULTS: Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02).

CONCLUSIONS: This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.}, } @article {pmid39557995, year = {2024}, author = {Enichen, EJ and Heydari, K and Wang, S and Nickel, GC and Kvedar, JC}, title = {The utility of personal wearable data in long COVID and personalized patient care.}, journal = {NPJ digital medicine}, volume = {7}, number = {1}, pages = {326}, pmid = {39557995}, issn = {2398-6352}, abstract = {Radin et al.’s recent study on patients with long COVID demonstrates that personal wearable data can provide critical insight into complex conditions. This editorial argues that research insights gained through personal wearables support the integration of personal wearables into healthcare. Challenges in incorporating wearable data in the clinic point towards AI data sorting, data sharing, device interoperability, FDA oversight, and expanded insurance coverage as first steps towards addressing these challenges.}, } @article {pmid39556251, year = {2024}, author = {Jeffrey, K and Hammersley, V and Maini, R and Crawford, A and Woolford, L and Batchelor, A and Weatherill, D and White, C and Millington, T and Kerr, R and Basetti, S and Macdonald, C and Quint, JK and Kerr, S and Shah, SA and Kurdi, A and Simpson, CR and Katikireddi, SV and Rudan, I and Robertson, C and Ritchie, L and Sheikh, A and Daines, L}, title = {Deriving and validating a risk prediction model for long COVID: a population-based, retrospective cohort study in Scotland.}, journal = {Journal of the Royal Society of Medicine}, volume = {117}, number = {12}, pages = {402-414}, pmid = {39556251}, issn = {1758-1095}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Scotland/epidemiology ; Male ; Female ; Retrospective Studies ; Middle Aged ; Adult ; Risk Factors ; Aged ; Risk Assessment ; SARS-CoV-2 ; Body Mass Index ; Age Factors ; Electronic Health Records ; Young Adult ; }, abstract = {OBJECTIVES: Using electronic health records, we derived and internally validated a prediction model to estimate risk factors for long COVID and predict individual risk of developing long COVID.

DESIGN: Population-based, retrospective cohort study.

SETTING: Scotland.

PARTICIPANTS: Adults (≥18 years) with a positive COVID-19 test, registered with a general medical practice between 1 March 2020 and 20 October 2022.

MAIN OUTCOME MEASURES: Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for predictors of long COVID, and patients' predicted probabilities of developing long COVID.

RESULTS: A total of 68,486 (5.6%) patients were identified as having long COVID. Predictors of long COVID were increasing age (aOR: 3.84; 95% CI: 3.66-4.03 and aOR: 3.66; 95% CI: 3.27-4.09 in first and second splines), increasing body mass index (BMI) (aOR: 3.17; 95% CI: 2.78-3.61 and aOR: 3.09; 95% CI: 2.13-4.49 in first and second splines), severe COVID-19 (aOR: 1.78; 95% CI: 1.72-1.84); female sex (aOR: 1.56; 95% CI: 1.53-1.60), deprivation (most versus least deprived quintile, aOR: 1.40; 95% CI: 1.36-1.44), several existing health conditions. Predictors associated with reduced long COVID risk were testing positive while Delta or Omicron variants were dominant, relative to when the Wild-type variant was dominant (aOR: 0.85; 95% CI: 0.81-0.88 and aOR: 0.64; 95% CI: 0.61-0.67, respectively) having received one or two doses of COVID-19 vaccination, relative to unvaccinated (aOR: 0.90; 95% CI: 0.86-0.95 and aOR: 0.96; 95% CI: 0.93-1.00).

CONCLUSIONS: Older age, higher BMI, severe COVID-19 infection, female sex, deprivation and comorbidities were predictors of long COVID. Vaccination against COVID-19 and testing positive while Delta or Omicron variants were dominant predicted reduced risk.}, } @article {pmid39554298, year = {2024}, author = {Tsuchida, T and Hirose, M and Fujii, H and Hisatomi, R and Ishizuka, K and Inoue, Y and Katayama, K and Nakagama, Y and Kido, Y and Matsuda, T and Ohira, Y}, title = {Evaluation of diseases complicating long COVID: A retrospective chart review.}, journal = {Journal of general and family medicine}, volume = {25}, number = {6}, pages = {324-332}, pmid = {39554298}, issn = {2189-7948}, abstract = {BACKGROUND: Evidence for the pathogenesis and treatment of postacute coronavirus disease 2019 (COVID-19) (long COVID) is lacking. As long COVID symptoms are predicted to have an impact on the global economy, clarification of the pathogenesis is urgently needed. Our experiences indicated that some symptoms were complicated by diseases established before the COVID-19 pandemic.

METHODS: Using a retrospective, cross-sectional study, we aimed to evaluate the diseases complicating long COVID. Using the medical records of patients with confirmed COVID-19 exhibiting residual symptoms lasting ≥60 days postinfection who visited our clinic in January 2021-February 2023, we investigated the symptoms and diseases observed. We identified diseases that occurred after COVID-19 and excluded those that were exacerbations of existing diseases.

RESULTS: During the first visit, the most common symptoms reported in a total of 798 patients were fatigue (523 patients), anxiety (349 patients), and lack of motivation (344 patients). Complicating diseases were observed in 452 patients (57%). There were 115, 65, and 60 patients with postural tachycardia syndrome, postural syndrome without tachycardia, and mood disorders, respectively. Some diseases requiring immediate treatment included pulmonary thromboembolism, purulent shoulder arthritis, cerebellopontine angle tumors, myasthenia gravis, and cervical myelopathy.

CONCLUSION: Not all symptoms that occur after COVID-19 should be treated as long COVID. Similar to normal medical treatment, a list of differential diagnoses should be maintained based on symptoms to obtain definitive diagnoses.}, } @article {pmid39553000, year = {2024}, author = {Hung, LW and Liu, MY and Yu, T and Hung, KC and Tsai, YW and Lai, CC and Wu, JY}, title = {Zinc Deficiency and Post-acute Outcomes in Patients With COVID-19: A Six-Month Retrospective Cohort Analysis of 3,726 Patients.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e71609}, pmid = {39553000}, issn = {2168-8184}, abstract = {Background Previous studies have suggested that zinc deficiency (ZD) may increase the risk of short-term mortality in patients with coronavirus disease 2019 (COVID-19). However, the relationship between zinc status and post-acute COVID-19 outcomes remains unclear. This study aimed to determine the association between ZD and long-term outcomes in patients with COVID-19. Methodology We conducted a retrospective cohort study using the TriNetX database, including patients aged 18 years or older diagnosed with COVID-19 between January 1, 2022, and July 31, 2023. Patients had documented serum or plasma zinc levels within three months before COVID-19 diagnosis and were not deceased or hospitalized in the first month of infection. They were categorized into ZD (zinc levels <70 μg/dL) and control (zinc levels ≥70 μg/dL) groups. After 1:1 propensity score matching for demographic and clinical variables, outcomes were assessed from 30 to 180 days post-diagnosis, including all-cause hospitalization, all-cause mortality, and four subphenotypes of post-acute COVID-19. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results After matching, each group included 1,863 patients with balanced baseline characteristics. The ZD group had a higher incidence of all-cause hospitalization (25.3% vs. 20.3%; HR = 1.314; 95% CI = 1.148-1.505; p < 0.001) and all-cause mortality (3.8% vs. 2.2%; HR = 1.735; 95% CI = 1.180-2.551; p = 0.045) compared to the control group during the follow-up period. Among the four subphenotypes, only the cardiac and renal subphenotype showed a significantly higher risk in the ZD group (HR = 1.099; 95% CI = 1.002-1.205; p = 0.004). Conclusions ZD is associated with increased risks of long-term hospitalization, mortality, and increased risk in COVID-19 patients with cardiac and renal comorbidities. Monitoring and managing zinc levels may be important for improving long-term outcomes. Further research is warranted to explore the potential benefits of zinc supplementation in COVID-19 patients with ZD.}, } @article {pmid39552393, year = {2024}, author = {Monistrol-Mula, A and Felez-Nobrega, M and Byrne, EM and Lind, PA and Hickie, IB and Martin, NG and Medland, SE and Colodro-Conde, L and Mitchell, BL}, title = {The effect of polygenic liability to mental disorders on COVID-19 outcomes in people with depression: the mediating role of anxiety.}, journal = {Psychological medicine}, volume = {54}, number = {15}, pages = {1-10}, pmid = {39552393}, issn = {1469-8978}, abstract = {BACKGROUND: Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression.

METHODS: Data from three assessments of the Australian Genetics of Depression Study (N = 4405; 52.2 years ± 14.9; 76.2% females) were analyzed. Outcomes included COVID-19 clinical outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and long COVID, noting the low incidence of COVID-19 cases in Australia at that time) and COVID-19 psychological outcomes (COVID-related stress and COVID-19 burnout). Predictors included PRS for depression, bipolar disorder, schizophrenia, and anxiety. The associations between these PRSs and the outcomes were assessed with adjusted linear/logistic/multinomial regressions. Mediation (N = 4338) and moderation (N = 3326) analyses were performed to explore the potential influence of anxiety symptoms and resilience on the identified associations between the PRSs and COVID-19 psychological outcomes.

RESULTS: None of the selected PRS predicted SARS-CoV-2 infection or long COVID. In contrast, the depression PRS predicted higher levels of COVID-19 burnout. Anxiety symptoms fully mediated the association between the depression PRS and COVID-19 burnout. Resilience did not moderate this association.

CONCLUSIONS: A higher genetic risk for depression predicted higher COVID-19 burnout and this association was fully mediated by anxiety symptoms. Interventions targeting anxiety symptoms may be effective in mitigating the psychological effects of a pandemic among people with depression.}, } @article {pmid39551951, year = {2024}, author = {Yao, L and Devotta, H and Li, J and Lunjani, N and Sadlier, C and Lavelle, A and Albrich, WC and Walter, J and O'Toole, PW and O'Mahony, L}, title = {Dysrupted microbial tryptophan metabolism associates with SARS-CoV-2 acute inflammatory responses and long COVID.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2429754}, pmid = {39551951}, issn = {1949-0984}, mesh = {Humans ; *Tryptophan/metabolism/blood ; *COVID-19/immunology/microbiology ; *Gastrointestinal Microbiome ; Male ; Female ; *SARS-CoV-2/immunology ; *Cytokines/blood/metabolism ; Middle Aged ; Aged ; *Feces/microbiology/virology ; Post-Acute COVID-19 Syndrome ; Indoles/metabolism ; Indoleacetic Acids/metabolism/blood ; Inflammation ; Adult ; Dysbiosis/microbiology ; }, abstract = {Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of long COVID has been associated with the depletion or over-abundance of specific taxa within the gut microbiome. However, the microbial mechanisms mediating these effects are not yet known. We hypothesized that altered microbial production of tryptophan and its downstream derivatives might contribute to inappropriate immune responses to viral infection. In patients hospitalized with COVID-19 (n = 172), serum levels of tryptophan and indole-3-propionate (IPA) negatively correlated with serum levels of many proinflammatory mediators (including C-reactive protein and Serum amyloid A), while C-glycosyltryptophan (C-Trp), indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) levels were positively correlated with levels of acute phase proteins, proinflammatory cytokines, alarmins and chemokines. A similar pattern was observed in long COVID patients (n = 20) where tryptophan and IPA were negatively associated with a large number of serum cytokines, while C-Trp and IAA were positively associated with circulating cytokine levels. Metagenomic analysis of the fecal microbiota showed the relative abundance of genes encoding the microbial enzymes required for tryptophan production (e.g. anthranilate synthase) and microbial tryptophan metabolism was significantly lower in patients hospitalized with COVID-19 (n = 380) compared to healthy controls (n = 270). Microbial tryptophan metabolites reduced innate cell proinflammatory responses to cytosolic DNA sensor Stimulator of interferon genes (STING), toll-like receptor (TLR)-3 and TLR-4 stimulation in vitro, while IL-10 secretion was enhanced. Microbial tryptophan metabolites also modified ex vivo human lymphocyte responses by limiting the production of TH1 and TH17 associated cytokines, while enhancing secretion of IL-22. These data suggest that lower levels of tryptophan production and tryptophan metabolism by gut microbes may increase the risk of severe and chronic outcomes to SARS-CoV-2 infection due to impaired innate and adaptive responses to infection. Screening patients for lower-level microbiome capacity for tryptophan metabolism may help identify at-risk individuals.}, } @article {pmid39551591, year = {2024}, author = {Luedtke, L and Haller-Wolf, J and Kriston, L and Koch, U and Nienhaus, A and Härter, M}, title = {Post-COVID in healthcare workers and its consequences on quality of life, activities, participation, need for rehabilitation and care experiences: protocol of a cohort study.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e083422}, pmid = {39551591}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology/rehabilitation/psychology ; *Quality of Life ; *Health Personnel/psychology ; Cohort Studies ; *SARS-CoV-2 ; Germany/epidemiology ; Male ; Post-Acute COVID-19 Syndrome ; Female ; Health Status ; Adult ; }, abstract = {INTRODUCTION: Healthcare workers (HCWs) have been of particular relevance for overcoming the SARS-CoV-2 pandemic. At the same time they have been affected by SARS-CoV-2 infections with above average probability. Around 6.5% of the overall infected persons are likely to develop persistent symptoms resulting from the infection, known as long-COVID or post-COVID syndrome (PCS). The aim of this study is (1) to investigate the prevalence, course and characteristics of PCS in German HCWs, (2) to examine its effects on psychosocial variables, (3) to identify rehabilitation and healthcare needs and (4) to analyse treatment experiences.

METHODS AND ANALYSIS: In a cohort study with a randomised selection of participants (N=20 000) from the Employer's Liability Insurance Association for Health and Welfare Care, the health status of HCWs, who had COVID-19 in their professional context will be examined. There will be two measurement points: baseline (T1) and a 12-month follow-up (T2). The outcome measures are the health status with a particular focus on persistent or newly occurring symptoms after a SARS-CoV-2 infection, health-related quality of life, functional capacity, the subjective need for and utilisation of healthcare services. Pre-existing conditions, the course of the acute infection and sociodemographic factors are considered as predictors. An advisory board made up of affected HCWs supports the study by contributing to the surveys' contents.

ETHICS AND DISSEMINATION: The study has been approved by the Local Ethics Committee of the Center for Psychosocial Medicine at the University Hospital Hamburg-Eppendorf (LPEK-0518). For dissemination, the results will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders in general and rehabilitation medicine.

TRAIL REGISTRATION NUMBER: https://drks.de/search/de/trial/DRKS00029314.}, } @article {pmid39551439, year = {2024}, author = {Wurm, J and Ritz, N and Zimmermann, P}, title = {Coronavirus disease 2019 (COVID-19) in children: Evolving epidemiology, immunology, symptoms, diagnostics, treatment, post-COVID-19 conditions, prevention strategies, and future directions.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2024.11.012}, pmid = {39551439}, issn = {1097-6825}, abstract = {The epidemiology of coronavirus disease 2019 (COVID-19) in children has evolved throughout the pandemic, with initially low infection rates rising significantly as a result of the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The immune response in children leads to milder symptoms compared to adults, with fever and cough being most frequent; tough symptoms vary by SARS-CoV-2 variant and age. Diagnostic methods to confirm current or past infection include reverse transcription PCR, rapid antigen tests, and serology. Treatment is mainly supportive, with antivirals and glucocorticoids reserved for severe cases. While serious conditions like multisystem inflammatory syndrome in children and other post-COVID-19 conditions are rare, they require careful management. Vaccination has proven effective in reducing severe disease and protecting against post-COVID-19 conditions. Continued surveillance, including wastewater monitoring and universal or pooled testing, remains crucial for controlling community spread. Key questions remain regarding the duration and quality of immunity after reinfection or vaccination, the impact of coinfections, and optimal treatment protocols for different pediatric populations.}, } @article {pmid39550783, year = {2024}, author = {Reyes, Z and Stovall, MC and Punyamurthula, S and Longo, M and Maraganore, D and Solch-Ottaiano, RJ}, title = {The impact of gut microbiome and diet on post-acute sequelae of SARS-CoV-2 infection.}, journal = {Journal of the neurological sciences}, volume = {467}, number = {}, pages = {123295}, doi = {10.1016/j.jns.2024.123295}, pmid = {39550783}, issn = {1878-5883}, mesh = {Humans ; Brain-Gut Axis/immunology ; *COVID-19/complications/diet therapy/immunology/virology ; *Diet, Mediterranean ; *Gastrointestinal Microbiome/immunology ; *Post-Acute COVID-19 Syndrome/immunology/microbiology/prevention & control ; SARS-CoV-2/immunology/pathogenicity ; }, abstract = {Long COVID, also known as Post COVID-19 condition by the World Health Organization or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is defined as the development of symptoms such as post-exertional malaise, dysgeusia, and partial or full anosmia three months after initial SARS-CoV-2 infection. The multisystem effects of PASC make it difficult to distinguish from its mimickers. Further, a comprehensive evaluation of the gut microbiome, nutrition, and PASC has yet to be studied. The gut-brain axis describes bidirectional immune, neural, endocrine, and humoral modulatory interactions between the gut microbiome and brain function. We explore recent studies that support an association between alterations in gut microbiome diversity and the severity of acute-phase COVID-19, and how these may be affected by diets rich in antioxidants and fiber. The Mediterranean Diet (MeDi) has demonstrated promising neuroprotective effects through its anti-inflammatory processes. Further, diets rich in fiber increase gut diversity and increase the amount of short-chain fatty acids (SCFAs) within the body-both shown to protect from acute COVID-19 complications. Long-term changes to the gut microbiome persist after acute infection and may increase susceptibility to PASC. This study builds on existing knowledge of determinants of PASC and highlights a relationship between nutrition, gut microbiome, acute-phase COVID-19, and, subsequently, PASC susceptibility.}, } @article {pmid39550693, year = {2024}, author = {Reagin, KL and Lee, RL and Williams, LA and Cocciolone, L and Funk, KE}, title = {Compromised CD8+ T cell immunity in the aged brain increases severity of neurotropic coronavirus infection and postinfectious cognitive impairment.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14409}, doi = {10.1111/acel.14409}, pmid = {39550693}, issn = {1474-9726}, support = {R00AG053412/AG/NIA NIH HHS/United States ; R00AG053412-04S1/AG/NIA NIH HHS/United States ; }, abstract = {Advanced age increases the risk of severe disease from SARS-CoV-2 infection, as well as incidence of long COVID and SARS-CoV-2 reinfection. We hypothesized that perturbations in the aged antiviral CD8[+] T cell response predisposes elderly individuals to severe coronavirus infection, re-infection, and postinfectious cognitive sequelae. Using MHV-A59 as a murine model of respiratory coronavirus, we found that aging increased CNS infection and lethality to MHV infection. This was coupled with increased CD8[+] T cells within the aged CNS but reduced antigen specificity. Aged animals also displayed a decreased proportion of CD103[+] resident memory cells (TRM), which correlated with increased severity of secondary viral challenge. Using a reciprocal adoptive transfer paradigm, data show that not only were fewer aged CD8[+] T cells retained within the adult brain post-infection, but also that adult CD8[+] cells expressed lower levels of TRM marker CD103 when in the aged microenvironment. Furthermore, aged animals demonstrated spatial learning impairment following MHV infection, which worsened in both aged and adult animals following secondary viral challenge. Spatial learning impairment was accompanied by increased TUNEL positivity in hippocampal neurons, suggestive of neuronal apoptosis. Additionally, primary cell coculture showed that activated CD8[+] T cells induced TUNEL positivity in neurons, independent of antigen-specificity. Altogether, these results show that non-antigen specific CD8[+] T cells are recruited to the aged brain and cause broad neuronal death without establishing a TRM phenotype that confers lasting protection against a secondary infection.}, } @article {pmid39550105, year = {2025}, author = {Calabrese, LH and Calabrese, C}, title = {Long COVID for the Rheumatologist: Current Understanding and Approach to Management.}, journal = {Rheumatic diseases clinics of North America}, volume = {51}, number = {1}, pages = {29-43}, doi = {10.1016/j.rdc.2024.08.004}, pmid = {39550105}, issn = {1558-3163}, mesh = {Humans ; *COVID-19/complications/therapy ; *Post-Acute COVID-19 Syndrome ; *Rheumatic Diseases/therapy ; Rheumatologists ; SARS-CoV-2 ; Rheumatology/methods ; Fibromyalgia/therapy ; }, abstract = {There are estimated tens of millions of individuals throughout the world suffering from a variety of postinfectious sequela following infection with severe acute respiratory syndrome coronavirus 2 also commonly referred to as long coronavirus disease (COVID). Long COVID is providing an opportunity for the field of rheumatology to explore the relationship between similar syndromes including fibromyalgia seen in patients with underlying inflammatory and noninflammatory rheumatic diseases, as well as other postacute infectious sequela and bring our field's traditional skill sets to bear on improving our understanding of these disorders and the care of such patients.}, } @article {pmid39549937, year = {2025}, author = {Mauro, M and Bestiaco, N and Zulian, E and Markežič, MM and Bignolin, I and Larese Filon, F}, title = {Manual dexterity, tactile perception and inflammatory profile in HCWs affected by long Covid: A case - control study.}, journal = {Life sciences}, volume = {360}, number = {}, pages = {123234}, doi = {10.1016/j.lfs.2024.123234}, pmid = {39549937}, issn = {1879-0631}, } @article {pmid39549783, year = {2025}, author = {de Bruijn, S and Tulen, AD and Rodenburg, J and Boshuizen, H and Schipper, M and Mutubuki, EN and Knoop, H and Franz, E and van der Maaden, T and van den Hof, S and van Hoek, AJ and van den Wijngaard, CC}, title = {Post-acute sequelae of COVID-19 3 to 12 months after infection: Delta vs Omicron.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {150}, number = {}, pages = {107302}, doi = {10.1016/j.ijid.2024.107302}, pmid = {39549783}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology/complications ; *SARS-CoV-2 ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Prospective Studies ; Aged ; Prevalence ; Netherlands/epidemiology ; Fatigue/etiology/epidemiology ; Dyspnea/epidemiology/etiology/virology ; Cognitive Dysfunction/epidemiology/virology/etiology ; Case-Control Studies ; Time Factors ; Severity of Illness Index ; }, abstract = {OBJECTIVES: Studies have shown temporal changes in post-acute sequelae of COVID-19 (PASC) prevalence for early SARS-CoV-2 variants, although often lacking controls. This prospective study assesses the prevalence of symptoms in Delta- and Omicron-infected cases up to 12 months compared with population controls.

METHODS: Adult participants filled out surveys every 3 months (T0-T12) between July 2021 and August 2023. Cases were recruited with a positive SARS-CoV-2 test during the Delta or Omicron domination. Population controls were randomly invited from the Dutch Personal Records Database. Participants indicated the presence of 13 PASC-associated symptoms, and severity scores of fatigue, cognitive impairment, dyspnea, and pain. PASC prevalence was defined as the excess prevalence of havingat least one PASC-associated symptom in cases compared with population controls.

RESULTS: PASC prevalence was 34.3% at T3 and decreased to 21.7% at T12 for Delta and decreased from 18.7% at T3 to 16.7% at T12 for Omicron. At T12, the difference between Delta and Omicron was not significant. Delta cases generally had higher excess symptom scores for fatigue, dyspnea, and cognitive impairment than Omicron.

CONCLUSIONS: In the first 9 months after infection, PASC prevalence was higher for Delta than Omicron, but the difference reduced over time and approximated after 12 months.}, } @article {pmid39547729, year = {2025}, author = {Vrettou, CS and Jolley, SE and Mantziou, V and Dimopoulou, I}, title = {Clinical Comparison of Post-intensive Care Syndrome and Long Coronavirus Disease.}, journal = {Critical care clinics}, volume = {41}, number = {1}, pages = {89-102}, doi = {10.1016/j.ccc.2024.08.009}, pmid = {39547729}, issn = {1557-8232}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Critical Care ; Post-Acute COVID-19 Syndrome ; Critical Illness ; Cognitive Dysfunction/etiology/physiopathology ; Risk Factors ; }, abstract = {Post-intensive care syndrome (PICS) encompasses persistent physical, psychological, and cognitive impairments. The coronavirus disease of 2019 (COVID-19) pandemic highlighted parallels between PICS and "long COVID". There is an overlap between the 2 in risk factors, symptoms, and pathophysiology. Physical impairments in both include weakness and fatigue. Cognitive impairments include executive dysfunction in PICS and "brain fog" in long COVID. Mental health issues consist of depression, anxiety, and posttraumatic stress disorder in both disease states. Long COVID and PICS impact families, with multifaceted effects on physical health, mental well-being, and socioeconomic stability. Understanding these syndromes is crucial for comprehensive patient care and family support.}, } @article {pmid39545965, year = {2024}, author = {Pawlik, MT and Rinneberg, G and Koch, A and Meyringer, H and Loew, TH and Kjellberg, A}, title = {Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1797-1817}, pmid = {39545965}, issn = {1433-8491}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *COVID-19/therapy/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.}, } @article {pmid39544193, year = {2024}, author = {Leitner, BP and Joseph, P and Quast, AF and Ramirez, MA and Heerdt, PM and Villalobos, JG and Singh, I}, title = {The metabolic and physiologic impairments underlying long COVID associated exercise intolerance.}, journal = {Pulmonary circulation}, volume = {14}, number = {4}, pages = {e70009}, pmid = {39544193}, issn = {2045-8932}, abstract = {Data from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO2), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO2 and exercise capacity (VO2) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO2 with reduced peak VO2 (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO2 [88% predicted (IQR 81% - 108%) vs. 70% predicted (IQR 64% - 89%); p = 0.02] and EO2 [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection. In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO2 was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO2 and consequently peak VO2 impact long COVID patients in a severity dependent manner. Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.}, } @article {pmid39543596, year = {2024}, author = {Floridia, M and Giuliano, M and Weimer, LE and Ciardi, MR and Agostoni, P and Palange, P and Rovere Querini, P and Zucco, S and Tosato, M and Lo Forte, A and Bonfanti, P and Lacedonia, D and Barisione, E and Figliozzi, S and Andreozzi, P and Damiano, C and Pricci, F and Onder, G and , }, title = {Symptom profile, case and symptom clustering, clinical and demographic characteristics of a multicentre cohort of 1297 patients evaluated for Long-COVID.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {532}, pmid = {39543596}, issn = {1741-7015}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/diagnosis ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; *SARS-CoV-2 ; Aged ; Retrospective Studies ; Cluster Analysis ; Cohort Studies ; Prospective Studies ; Fatigue/epidemiology ; Severity of Illness Index ; Dyspnea/epidemiology/physiopathology ; }, abstract = {BACKGROUND: Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity.

METHODS: Multicentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering.

RESULTS: The study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile.

CONCLUSIONS: The findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations.}, } @article {pmid39542232, year = {2025}, author = {Park, E and Liu, E and Baker, AJ}, title = {In vivo characterization of ACE2 expression in Sprague-Dawley rats and cultured primary brain pericytes highlights the utility of Rattus norvegicus in the study of COVID-19 brain pathophysiology.}, journal = {Brain research}, volume = {1848}, number = {}, pages = {149333}, doi = {10.1016/j.brainres.2024.149333}, pmid = {39542232}, issn = {1872-6240}, mesh = {Animals ; *Pericytes/metabolism/virology ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; *COVID-19/metabolism/pathology ; *Brain/metabolism ; Rats ; *Rats, Sprague-Dawley ; *SARS-CoV-2/pathogenicity ; Cells, Cultured ; Spike Glycoprotein, Coronavirus/metabolism ; Male ; Humans ; Disease Models, Animal ; Endothelial Cells/metabolism ; }, abstract = {A high number of COVID-19 patients report ongoing neurological impairments including headache, fatigue and memory impairments. Our understanding of COVID-19 disease mechanisms in the brain is limited and relies on post-mortem human tissues, in vitro studies in various cell lines (both human and animal) as well as preclinical studies in a variety of species. Notably the use of rats in the study of COVID-19 has been scarce in part due to early reports of low infectivity of the original Wuhan strain in mice and rats. Evidence has shown that subsequent strains that have mutated from the original strain are capable of infection in rats. Here we present an immunohistological characterization of ACE2 expression in the rat brain perivascular region. We found ACE2 to be expressed in pericytes but not endothelial cells or astrocytes in the perivascular space. We further examined the uptake of Omicron variants 1.1.529 and BA.2 receptor binding domains (RBD) of the SARS-CoV2 spike protein in primary brain pericytes derived from rats. We demonstrate that rat primary brain pericytes are susceptible to SARS-CoV2 spike protein uptake and induce functional changes in pericytes associated with a reduction in tight junction protein expression. These data provide evidence that rat primary cell responses to SARS-CoV2 infection are consistent with reports of infectivity in other species (transgenic mice expressing hACE2, ferrets, hamsters) and supports the use of this model organism with a long history of use in the study of disease which should be leveraged for study of COVID-19 in the brain.}, } @article {pmid39540209, year = {2024}, author = {Lee, A and Davido, B and Beck, E and Demont, C and Joshi, K and Kohli, M and Maschio, M and Uhart, M and El Mouaddin, N}, title = {Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France.}, journal = {Human vaccines & immunotherapeutics}, volume = {20}, number = {1}, pages = {2423474}, pmid = {39540209}, issn = {2164-554X}, mesh = {Humans ; *COVID-19/prevention & control/economics/immunology/epidemiology ; France/epidemiology ; *Immunocompromised Host ; *Hospitalization/economics/statistics & numerical data ; *SARS-CoV-2/immunology ; *BNT162 Vaccine/immunology/economics ; Middle Aged ; Adult ; *2019-nCoV Vaccine mRNA-1273/immunology/economics ; *Cost of Illness ; *COVID-19 Vaccines/economics/immunology/administration & dosage ; *Quality-Adjusted Life Years ; Aged ; Vaccine Efficacy ; Female ; Male ; Cost-Benefit Analysis ; Incidence ; }, abstract = {An evaluation was conducted to predict the economic and clinical burden of vaccinating all immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines versus BNT162b2 variant-adapted vaccines in Fall 2023 and Spring 2024 in France. The number of symptomatic SARS-CoV-2 infections, hospitalizations or deaths due to COVID-19, and long COVID cases, costs and quality-adjusted life years (QALYs) were estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from the original and BA.4/5 variant-adapted vaccines, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were evaluated in sensitivity analyses. In an ideal situation where 100% coverage is achieved, the mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs gained. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.}, } @article {pmid39537445, year = {2024}, author = {Obraitis, D and Li, D}, title = {Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities.}, journal = {Current opinion in virology}, volume = {68-69}, number = {}, pages = {101437}, doi = {10.1016/j.coviro.2024.101437}, pmid = {39537445}, issn = {1879-6265}, mesh = {*Fatigue Syndrome, Chronic/virology/blood ; Humans ; *Virome ; *COVID-19/virology ; SARS-CoV-2/genetics ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with a complex clinical presentation and an unknown etiology. Various viral infections have been proposed as potential triggers of ME/CFS onset, but no specific pathogen has been identified in all cases of postinfectious ME/CFS. The symptomatology of the postacute sequelae of SARS-CoV-2, or long COVID, mirrors that of ME/CFS, with nearly half of long COVID patients meeting ME/CFS diagnostic criteria. The influx of newly diagnosed patients has reinvigorated interest in ME/CFS pathogenesis research, with an emphasis on viral triggers. This review summarizes the current understanding of ME/CFS research on viral triggers, including blood virome screening studies. To further elucidate the molecular basis of ME/CFS, there is a need to develop innovative bioinformatics tools capable of analyzing complex virome data and integrating multiomics information.}, } @article {pmid39537389, year = {2024}, author = {Wang, J and Goodfellow, H and Walker, S and Blandford, A and Pfeffer, P and Hurst, JR and Sunkersing, D and Bradbury, K and Robson, C and Henley, W and Gomes, M}, title = {Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e088538}, pmid = {39537389}, issn = {2044-6055}, mesh = {Humans ; *Quality of Life ; *COVID-19/economics ; Male ; Female ; Longitudinal Studies ; Middle Aged ; *Fatigue ; Cost of Illness ; Health Care Costs/statistics & numerical data ; Adult ; SARS-CoV-2 ; Aged ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

DESIGN: A population-based longitudinal cohort study using real-time user data.

SETTING: 35 specialised long COVID clinics in the UK.

PARTICIPANTS: 4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

MAIN OUTCOME MEASURES: Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

RESULTS: The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was -0.86 (95% CI -1.32, -0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

CONCLUSIONS: Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.}, } @article {pmid39536394, year = {2024}, author = {Wang, L and Yin, Y and Glampson, B and Peach, R and Barahona, M and Delaney, BC and Mayer, EK}, title = {Transformer-based deep learning model for the diagnosis of suspected lung cancer in primary care based on electronic health record data.}, journal = {EBioMedicine}, volume = {110}, number = {}, pages = {105442}, pmid = {39536394}, issn = {2352-3964}, mesh = {Humans ; *Electronic Health Records ; *Lung Neoplasms/diagnosis ; *Primary Health Care ; *Deep Learning ; Case-Control Studies ; Female ; Early Detection of Cancer/methods ; Male ; Middle Aged ; Aged ; ROC Curve ; }, abstract = {BACKGROUND: Due to its late stage of diagnosis lung cancer is the commonest cause of death from cancer in the UK. Existing epidemiological risk models in clinical usage, which have Positive Predictive Values (PPV) of less than 10%, do not consider the temporal relations expressed in sequential electronic health record (EHR) data. We aimed to build a model for lung cancer early detection in primary care using machine learning with deep 'transformer' models on EHR data to learn from these complex sequential 'care pathways'.

METHODS: We split the Whole Systems Integrated Care (WSIC) dataset into 70% training and 30% validation. Within the training set we created a case-control study with lung cancer cases and control cases of 'other' cancers or respiratory conditions or 'other' non cancer conditions. Based on 3,303,992 patients from January 1981 to December 2020 there were 11,847 lung cancer cases. 5789 cases and 7240 controls were used for training and 50,000 randomly selected patients out of the whole validation population of 368,906 for validation. GP EHR data going back three years from the date of diagnosis less the most recent one months were semantically pre-processed by mapping from more than 30,000 terms to 450. Model building was performed using ALBERT with a Logistic Regression Classifier (LRC) head. Clustering was explored using k-means. An additional regression model alone was built on the pre-processed data as a comparator.

FINDINGS: Our model achieved an AUROC of 0.924 (95% CI 0.921-0.927) with a PPV of 3.6% (95% CI 3.5-3.7) and Sensitivity of 86.6% (95% CI 85.3-87.8) based on the three year's data prior to diagnosis less the immediate month before index diagnosis. The comparator regression model achieved a PPV of 3.1% (95% CI 3.0-3.1) and AUROC of 0.887 (95% CI 0.884-0.889). We interpreted our model using cluster analysis and have identified six groups of patients exhibiting similar lung cancer progression patterns and clinical investigation patterns.

INTERPRETATION: Capturing temporal sequencing between cancer and non-cancer pathways to diagnosis enables much more accurate models. Future work will focus on external dataset validation and integration into GP clinical systems for evaluation.

FUNDING: Cancer Research UK.}, } @article {pmid39536123, year = {2024}, author = {Marrazzo, J and Gibbons, GH and Koroshetz, W}, title = {Initiating Long Covid RECOVERy.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eadr9971}, doi = {10.1126/scitranslmed.adr9971}, pmid = {39536123}, issn = {1946-6242}, mesh = {*COVID-19/epidemiology/virology ; Humans ; United States/epidemiology ; *National Institutes of Health (U.S.) ; *SARS-CoV-2/isolation & purification ; }, abstract = {The NIH's RECOVER Initiative aims to ease the suffering of those living with Long Covid.}, } @article {pmid39536122, year = {2024}, author = {Saydah, SH and Campbell, AP and Randolph, AG}, title = {Consequences beyond acute SARS-CoV-2 infection in children.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2099}, doi = {10.1126/scitranslmed.ado2099}, pmid = {39536122}, issn = {1946-6242}, mesh = {Humans ; *COVID-19/epidemiology/virology/complications ; Child ; *Systemic Inflammatory Response Syndrome ; *SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although most children are spared from developing complications from SARS-CoV-2 infection, some may suffer consequences including Long Covid and multisystem inflammatory syndrome in children (MIS-C). Although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention.}, } @article {pmid39536121, year = {2024}, author = {Peluso, MJ and Hanson, MR and Deeks, SG}, title = {Infection-associated chronic conditions: Why Long Covid is our best chance to untangle Osler's web.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2101}, doi = {10.1126/scitranslmed.ado2101}, pmid = {39536121}, issn = {1946-6242}, mesh = {Humans ; Chronic Disease ; *COVID-19/complications/virology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation & purification ; }, abstract = {The recognition of Long Covid has renewed efforts to understand other infection-associated chronic conditions (IACCs). Here, we describe how studies of Long Covid and other IACCs might inform one another. We argue for the importance of a coordinated research agenda addressing these debilitating illnesses.}, } @article {pmid39536120, year = {2024}, author = {Silva, J and Iwasaki, A}, title = {Sex differences in postacute infection syndromes.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2102}, doi = {10.1126/scitranslmed.ado2102}, pmid = {39536120}, issn = {1946-6242}, mesh = {Female ; Humans ; Male ; *Post-Acute COVID-19 Syndrome/epidemiology/virology ; Prevalence ; SARS-CoV-2/isolation & purification/pathogenicity ; *Sex Factors ; }, abstract = {Postacute infection syndromes like Long Covid disproportionately affect females, differing in prevalence, symptoms, and potential causes from males. This Viewpoint highlights these sex differences, gaps in current understanding, and the critical need for sex-based research.}, } @article {pmid39536118, year = {2024}, author = {Schäfer, A and Leist, SR and Powers, JM and Baric, RS}, title = {Animal models of Long Covid: A hit-and-run disease.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2104}, doi = {10.1126/scitranslmed.ado2104}, pmid = {39536118}, issn = {1946-6242}, mesh = {Animals ; *COVID-19/immunology/virology ; *Disease Models, Animal ; *SARS-CoV-2 ; Humans ; *Post-Acute COVID-19 Syndrome ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.}, } @article {pmid39536117, year = {2024}, author = {Hamlin, RE and Pienkos, SM and Chan, L and Stabile, MA and Pinedo, K and Rao, M and Grant, P and Bonilla, H and Holubar, M and Singh, U and Jacobson, KB and Jagannathan, P and Maldonado, Y and Holmes, SP and Subramanian, A and Blish, CA}, title = {Sex differences and immune correlates of Long Covid development, symptom persistence, and resolution.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eadr1032}, doi = {10.1126/scitranslmed.adr1032}, pmid = {39536117}, issn = {1946-6242}, mesh = {Humans ; *COVID-19/immunology ; Female ; Male ; *SARS-CoV-2/immunology ; *Sex Characteristics ; Middle Aged ; Adult ; NF-kappa B/metabolism ; Transforming Growth Factor beta/metabolism ; Post-Acute COVID-19 Syndrome ; Sex Factors ; Signal Transduction ; }, abstract = {Sex differences have been observed in acute coronavirus disease 2019 (COVID-19) and Long Covid (LC) outcomes, with greater disease severity and mortality during acute infection in males and greater proportions of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to LC pathogenesis. To investigate the immunologic underpinnings of LC development and symptom persistence, we performed multiomic analyses on blood samples obtained during acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 3 and 12 months after infection in a cohort of 45 participants who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Males who would later develop LC exhibited increases in transforming growth factor-β (TGF-β) signaling during acute infection, whereas females who would go on to develop LC had reduced TGFB1 expression. Females who developed LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, during acute infection compared with females who recovered. Many immune features of LC were also conserved across sexes, such as alterations in monocyte phenotype and activation state. Nuclear factor κB (NF-κB) transcription factors were up-regulated in many cell types at acute and convalescent time points. Those with ongoing LC demonstrated reduced ETS1 expression across lymphocyte subsets and elevated intracellular IL-4 in T cell subsets, suggesting that ETS1 alterations may drive aberrantly elevated T helper cell 2-like responses in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics.}, } @article {pmid39536116, year = {2024}, author = {Antar, AAR and Cox, AL}, title = {Translating insights into therapies for Long Covid.}, journal = {Science translational medicine}, volume = {16}, number = {773}, pages = {eado2106}, doi = {10.1126/scitranslmed.ado2106}, pmid = {39536116}, issn = {1946-6242}, mesh = {Humans ; *COVID-19/therapy/immunology/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Animals ; Translational Research, Biomedical ; }, abstract = {Long Covid is defined by a wide range of symptoms that persist after the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported symptoms include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other symptoms reported. Symptom range, duration, and severity are highly variable and partially overlap with symptoms of myalgic encephalomyelitis/chronic fatigue syndrome and other post-acute infectious syndromes, highlighting opportunities to define shared mechanisms of pathogenesis. Potential mechanisms of Long Covid are diverse, including persistence of viral reservoirs, dysregulated immune responses, direct viral damage of tissues targeted by SARS-CoV-2, inflammation driven by reactivation of latent viral infections, vascular endothelium activation or dysfunction, and subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, and microbiota dysbiosis. The heterogeneity of symptoms and baseline characteristics of people with Long Covid, as well as the varying states of immunity and therapies given at the time of acute infection, have made etiologies of Long Covid difficult to determine. Here, we examine progress on preclinical models for Long Covid and review progress being made in clinical trials, highlighting the need for large human studies and further development of models to better understand Long Covid. Such studies will inform clinical trials that will define treatments to benefit those living with this condition.}, } @article {pmid39534773, year = {2024}, author = {Nigro, M and Valenzuela, C and Arancibia, F and Cohen, M and Lam, DCL and Maves, RC and Rath, B and Simpson, SQ and Song, Y and Tsiodras, S and Chalmers, JD and Aliberti, S}, title = {A worldwide look into long COVID-19 management: an END-COVID survey.}, journal = {ERJ open research}, volume = {10}, number = {6}, pages = {}, pmid = {39534773}, issn = {2312-0541}, abstract = {BACKGROUND: Long COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide.

METHODS: A survey-based study investigating long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID and PATS). A global analysis of the results is provided here, alongside sub-population analysis based on continents, national income levels, type of involved healthcare professional and inclusion or exclusion of paediatric patients.

FINDINGS: 1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre.

INTERPRETATION: Long COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included.}, } @article {pmid39534771, year = {2024}, author = {Choi, H}, title = {A worldwide perspective of long COVID management: how can we END-COVID?.}, journal = {ERJ open research}, volume = {10}, number = {6}, pages = {}, pmid = {39534771}, issn = {2312-0541}, abstract = {A global survey revealed marked heterogeneity in long COVID management worldwide https://bit.ly/4dVTJ2t.}, } @article {pmid39529893, year = {2024}, author = {Meach, R and Carless, D and Sanal-Hayes, NEM and Mclaughlin, M and Hayes, LD and Mair, JL and Ormerod, J and Hilliard, N and Ingram, J and Sculthorpe, NF}, title = {An Adaptive Pacing Intervention for Adults Living With Long COVID: A Narrative Study of Patient Experiences of Using the PaceMe app.}, journal = {Journal of patient experience}, volume = {11}, number = {}, pages = {23743735241272158}, pmid = {39529893}, issn = {2374-3735}, abstract = {Adaptive pacing (AP) is a self-management technique which seeks to balance energy and rest in individuals with chronic health conditions. Adaptive pacing can help people with myalgic encephalomyelitis/chronic fatigue syndrome learn how to manage their energy expenditure thereby reducing their risk of post-exertional malaise (PEM) and other symptoms. Given some symptom similarity, AP also has rehabilitation potential for people experiencing disability from long COVID. The purpose of this study was to explore patient experiences of an AP intervention (the "PaceMe" app) to determine its value for individuals experiencing long COVID. Twenty-five participants each took part in two narrative interviews (at intervention start point and at 3-6 months). Data were analyzed using narrative thematic analysis. Our analysis identified 4 themes relating to key benefits of the PaceMe app: (1) PEM management, (2) Support, (3) Validation, and (4) Control and Agency. By illuminating the critical facts and centring patient voices, these findings contribute a better understanding of the experiences and needs of those with long COVID and highlight the value of a digital health intervention as a vital component of rehabilitation.}, } @article {pmid39526116, year = {2024}, author = {Kyriakopoulos, AM and Nigh, G and McCullough, PA and Seneff, S}, title = {Clinical rationale for dietary lutein supplementation in long COVID and mRNA vaccine injury syndromes.}, journal = {F1000Research}, volume = {13}, number = {}, pages = {191}, pmid = {39526116}, issn = {2046-1402}, mesh = {Humans ; *COVID-19/prevention & control ; COVID-19 Drug Treatment ; *COVID-19 Vaccines/administration & dosage/adverse effects ; *Dietary Supplements ; *Lutein/administration & dosage/therapeutic use ; mRNA Vaccines ; Olive Oil ; Oxidative Stress/drug effects ; Post-Acute COVID-19 Syndrome ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. High dietary intake of lutein is beneficial against eye disease, improves cardiometabolic health, protects from neurodegenerative diseases, and is beneficial for liver, kidney, and respiratory health. Lutein protects against oxidative and nitrosative stress, both of which play a major role in long COVID and mRNA vaccination injury syndromes. Lutein is an important natural agent for therapeutic use against oxidative and nitrosative stress in chronic illnesses such as cardiovascular and neurodegenerative diseases and cancer. It can also potentially inhibit spike protein-induced inflammation. Rich dietary supplementation of lutein, naturally derived in non-biodegradable Extra Virgin Olive Oil (EVOO), can most optimally be used against oxidative and nitrosative stress during post-COVID and mRNA vaccination injury syndromes. Due to its high oleic acid (OA) content, EVOO supports optimal absorption of dietary lutein. The main molecular pathways by which the SARS-CoV-2 spike protein induces pathology, nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and activated protein (AP)-1, can be suppressed by lutein. Synergy with other natural compounds for spike protein detoxification is likely.}, } @article {pmid39524912, year = {2024}, author = {Grach, SL and Dudenkov, DV and Pollack, B and Fairweather, D and Aakre, CA and Munipalli, B and Croghan, IT and Mueller, MR and Overgaard, JD and Bruno, KA and Collins, NM and Li, Z and Hurt, RT and Tal, MC and Ganesh, R and Knight, DTR}, title = {Overlapping conditions in Long COVID at a multisite academic center.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1482917}, pmid = {39524912}, issn = {1664-2295}, abstract = {BACKGROUND: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

METHODS: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

RESULTS: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

CONCLUSION: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.}, } @article {pmid39524607, year = {2024}, author = {Wang, WK and Jeong, H and Hershkovich, L and Cho, P and Singh, K and Lederer, L and Roghanizad, AR and Shandhi, MMH and Kibbe, W and Dunn, J and , }, title = {Tree-based classification model for Long-COVID infection prediction with age stratification using data from the National COVID Cohort Collaborative.}, journal = {JAMIA open}, volume = {7}, number = {4}, pages = {ooae111}, pmid = {39524607}, issn = {2574-2531}, abstract = {OBJECTIVES: We propose and validate a domain knowledge-driven classification model for diagnosing post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID, using Electronic Health Records (EHRs) data.

MATERIALS AND METHODS: We developed a robust model that incorporates features strongly indicative of PASC or associated with the severity of COVID-19 symptoms as identified in our literature review. The XGBoost tree-based architecture was chosen for its ability to handle class-imbalanced data and its potential for high interpretability. Using the training data provided by the Long COVID Computation Challenge (L3C), which was a sample of the National COVID Cohort Collaborative (N3C), our models were fine-tuned and calibrated to optimize Area Under the Receiver Operating characteristic curve (AUROC) and the F1 score, following best practices for the class-imbalanced N3C data.

RESULTS: Our age-stratified classification model demonstrated strong performance with an average 5-fold cross-validated AUROC of 0.844 and F1 score of 0.539 across the young adult, mid-aged, and older-aged populations in the training data. In an independent testing dataset, which was made available after the challenge was over, we achieved an overall AUROC score of 0.814 and F1 score of 0.545.

DISCUSSION: The results demonstrated the utility of knowledge-driven feature engineering in a sparse EHR data and demographic stratification in model development to diagnose a complex and heterogeneously presenting condition like PASC. The model's architecture, mirroring natural clinician decision-making processes, contributed to its robustness and interpretability, which are crucial for clinical translatability. Further, the model's generalizability was evaluated over a new cross-sectional data as provided in the later stages of the L3C challenge.

CONCLUSION: The study proposed and validated the effectiveness of age-stratified, tree-based classification models to diagnose PASC. Our approach highlights the potential of machine learning in addressing the diagnostic challenges posed by the heterogeneity of Long-COVID symptoms.}, } @article {pmid39524261, year = {2024}, author = {Agarwala, S and Vijayvargiya, M and Upadhyay, A}, title = {Transient Osteoporosis of Hip as a Part of "Long COVID-19": A Case Series.}, journal = {Journal of orthopaedic case reports}, volume = {14}, number = {11}, pages = {220-224}, pmid = {39524261}, issn = {2250-0685}, abstract = {INTRODUCTION: Transient osteoporosis of the hip (TOH) presents with symptoms such as groin pain, discomfort, and the presence of bone edema detected on magnetic resonance imaging (MRI) scans. We have observed an increase in the occurrence of TOH in patients following the COVID-19 pandemic.

CASE REPORT: In this series, we present four cases of TOH that developed after COVID-19 infection. The average cumulative dose of prednisolone exposure in these cases was 788 mg (range 300-1050 mg). The mean duration between diagnosis and COVID-19 infection was 102 days (range 90-123 days). The average duration from the resolution of symptoms to the initiation of bisphosphonate therapy was 98 days (range 90-120 days).

CONCLUSION: Bisphosphonate therapy appears to be an effective pharmacological treatment for TOH, providing rapid pain relief and shortening the disease's natural course. This study demonstrates positive outcomes, including normalized MRI results and no progression to avascular necrosis, suggesting bisphosphonates as a promising management option for TOH patients.}, } @article {pmid39532773, year = {2024}, author = {Dörr, T and Strahm, C and Güsewell, S and Ballouz, T and Kocan, E and Cusini, A and Goppel, S and Grässli, F and Möller, JC and Puhan, MA and Risch, L and Ruetti, M and Schlegel, M and Stocker, R and von Kietzell, M and Vuichard-Gysin, D and Kuster, SP and Kahlert, CR and Kohler, P and , }, title = {Burden of post-acute COVID-19 sequelae in healthcare workers and its course over a 30-month period-results from a prospective multicentre cohort.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {39532773}, issn = {1439-0973}, support = {YTCR 12/22//Schweizerische Akademie der Medizinischen Wissenschaften/ ; 31CA30_196544//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {PURPOSE: As healthcare workers (HCW) have been disproportionally affected by COVID-19, its post-acute sequelae (PASC) in HCW can impact healthcare systems. We assessed the burden and course of PASC in HCW over a 30-month period.

METHODS: In a prospective multicentre HCW cohort in Switzerland, PASC surveys were conducted in 03/2021, 09/2021, 06/2022, 04/2023, and 10/2023. Stratified by viral variant at first infection, the prevalence of PASC symptoms, self-experienced PASC and the Post-COVID Functional Status (PCFS) were analysed cross-sectionally in 10/2023, self-perceived success of therapeutic measures used was assessed. The evolution of PASC symptoms and PCFS in Wild-type and non-Wild-type infected HCW compared to uninfected controls was analysed longitudinally across all surveys.

RESULTS: In cross-sectional analysis, 1704 HCW (median age 47 years, 82.2% female) were included. Thereof, 30.7% reported ≥ 1 PASC symptom in 10/2023, with 115 (6.7%) stating to have or have had PASC. Both were most common after Wild-type infection compared to other variants. Overall, 17/115 (15%) indicated relevant/severe restrictions in their daily activities and of 85 (74%) that tried ≥ 1 measure against their symptoms, 69 (81%) reported having benefitted. Longitudinal analysis (n = 653) showed a significantly higher proportion of Wild-type infected HCW to report PASC symptoms compared to controls in 03/2021 (+ 21%, 95% CI 4-39), with decreasing trend (+ 7%, 95%CI -10-25 in 10/2023). This effect was not evident for non-Wild-type infected HCW.

CONCLUSIONS: Over a 30 month period, overall PASC burden in our HCW cohort decreased, although 1% still experience relevant restrictions in their daily life; Wild-type infected individuals show the highest disease burden.}, } @article {pmid39531278, year = {2024}, author = {Bock, J and Kung, S and Ganesh, R and Hurt, RT and Lapid, MI}, title = {Evaluating Repetitive Transcranial Magnetic Stimulation for Neuropsychiatric Symptoms in Long COVID: A Case Series.}, journal = {The journal of ECT}, volume = {}, number = {}, pages = {}, doi = {10.1097/YCT.0000000000001072}, pmid = {39531278}, issn = {1533-4112}, abstract = {OBJECTIVE: To describe the immediate clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in treating long COVID symptoms. Long COVID currently impacts approximately 5.3% of US adults, presenting with persistent fatigue, depression, anxiety, cognitive impairments, and social function decline. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has improved these symptoms in some studies.

METHODS: Five patients (ages 52-63 years, 3 female patients) underwent accelerated rTMS using intermittent theta burst stimulation (600 pulses over 3 minutes 20 seconds, 80%-120% of resting motor threshold) to the left dorsolateral prefrontal cortex. The treatment consisted of twice-daily sessions over 20-30 treatments. Outcomes were measured using the Patient-Reported Outcomes Measurement and Information System (PROMIS) questionnaires, assessing fatigue, depression, anxiety, cognitive function, and social function at baseline and immediately posttreatment.

RESULTS: One patient discontinued immediately due to intolerable scalp pain. Posttreatment PROMIS scores showed the following: fatigue decreased from 74.5 to 61.8, depression from 60.3 to 51.5, and anxiety from 62.0 to 54.0. Scores increased for cognitive (26.8 to 32.3) and social (31.0 to 32.5) function. These changes, although not statistically significant, indicate a trend toward symptom reduction. Subjectively, 3 of 4 patients who completed the rTMS course reported improvements.

CONCLUSION: This case series suggests that rTMS may offer symptomatic relief in long COVID patients. Although the observed improvements in PROMIS were not statistically significant, even minimal improvements are clinically significant for patients enduring prolonged suffering. These preliminary findings are encouraging and underscore the need for further research with larger cohorts to validate the efficacy of rTMS in long COVID symptom relief.}, } @article {pmid39529266, year = {2024}, author = {Natafgi, N and Parris, K and Walker, E and Gartner, T and Coffin, J and Mitcham, A and Ferrer, LS and Patel, MK and Wymbs, H and Kennedy, AB}, title = {Through Their Eyes: Using Photovoice to Capture the Capacity-Building Journey of Long Covid Patient Experts.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {6}, pages = {e70094}, pmid = {39529266}, issn = {1369-7625}, support = {//This study was supported by Patient-Centered Outcomes Research Institute (PCORI) Award (EASC-COVID-00293)./ ; }, mesh = {Humans ; *COVID-19 ; *Capacity Building ; *Photography ; *Patient Participation ; Female ; Male ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Middle Aged ; South Carolina ; Adult ; }, abstract = {BACKGROUND: Long Covid, characterised by persistent symptoms following the coronavirus disease 2019 (COVID-19) infection, significantly impacts the quality of life. Engaging patients in research and care through participatory methods can enhance a shared understanding of illness and improve the relevance of research.

OBJECTIVE: We define Patient Experts (PEs) as persons (including patients, caregivers and providers) who have completed a series of training sessions on team building, research methods and communication at the Patient Engagement Studio, University of South Carolina (PES USC). This study explores the use of photovoice to document the experiences and capacity-building journey of Long Covid PEs within PES USC.

METHODS: The study employed photovoice within the COVID-19-Focused Virtual Patient Engagement Studio (CoVIP Studio). PEs submitted photographs and narratives at two distinct time points. Among the 18 PEs who participated in the project, 47 photos were collected during the training, and 31 were collected at the project's conclusion. Thematic analysis was conducted to capture changes in patient perspectives and engagement.

RESULTS: Initial themes identified were "Hope through Community," "Collaborative Education and Research" and "Strength and Endurance." By the project's end, themes had evolved to "Working as a Team to Share and Acquire Knowledge," "Enhanced Confidence in the Future of Care" and "Perseverance and Progress." These findings highlight the transformative impact of patient engagement and the utility of photovoice in documenting longitudinal shifts in patient perspectives.

CONCLUSION: Photovoice effectively engaged Long Covid patients and captured their evolving roles and perceptions as PEs. The study underscores the value of patient-led participatory methods in enhancing the relevance and applicability of clinical research, advocating for their broader adoption to improve patient-centred care and research outcomes.

A CoVIP Studio stakeholder advisory board (CoVIP SAB) guided the co-development and implementation of this project. The CoVIP SAB comprised nine members with complementary skills and expertise, including three patients, three clinicians who provide care to patients with COVID-19 and three researchers with expertise in patient-centred research, COVID-19 and/or patient engagement and collaborate with patients as co-investigators. The board contributed to project design and implementation, refining photovoice prompts and shaping dissemination strategies. In addition, one PE who actively participated in all phases of the project contributed to the writing of this paper and is a coauthor. All project activities involved patients and/or caregivers with lived experience of Long Covid.}, } @article {pmid39527314, year = {2024}, author = {Chen, D and Li, X and Xiao, C and Xiao, W and Lou, L and Gao, Z}, title = {Identifying influencing factors and constructing a prediction model for long COVID-19 in hemodialysis patients.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, pmid = {39527314}, issn = {1573-2584}, abstract = {PURPOSE: This study aimed to identify the potential influencing factors and construct a prediction model for long COVID in hemodialysis patients.

METHODS: We retrospectively reviewed 115 patients undergoing hemodialysis in a tertiary hospital between December 2022 and January 2023. Both univariate and multivariate logistic regression models were applied to identify potential influencing factors, and the prediction model was constructed using an ROC curve.

RESULTS: Of the 115 included patients, 60 experienced long COVID, with a prevalence of 52.2%. The univariate analysis found that a three-dose COVID-19 vaccination was associated with a reduced risk of long COVID (OR: 0.10; 95%CI: 0.01-0.86; P = 0.036). However, severe COVID (OR: 9.49; 95%CI: 1.14-78.90; P = 0.037), undergoing CT examination (OR: 3.01; 95%CI: 1.34-6.78; P = 0.008), and abnormal neutrophil (OR: 5.95; 95%CI: 1.26-28.19; P = 0.025), and platelet (OR: 2.39; 95%CI: 1.11-5.13; P = 0.025) counts were associated with a higher risk of long COVID. After adjusting for potential confounding factors, undergoing CT examination (OR: 2.60; 95%CI: 1.02-6.64; P = 0.046) and having abnormal neutrophil (OR: 8.16; 95%CI: 1.57-42.38; P = 0.013) and monocyte (OR: 17.77; 95%CI: 1.30-242.29; P = 0.031) counts were associated with a higher risk of long COVID. The prediction model constructed based on these factors showed a relatively better predictive value (AUC: 0.738; 95%CI: 0.648-0.828; P < 0.001).

CONCLUSIONS: The risk of long COVID-19 in hemodialysis patients was significantly related to undergoing CT examination and having abnormal neutrophil and monocyte counts, and the prediction model constructed using these factors showed a moderate predictive value.}, } @article {pmid39522688, year = {2024}, author = {Almulla, AF and Maes, M and Zhou, B and Al-Hakeim, HK and Vojdani, A}, title = {Brain-targeted autoimmunity is strongly associated with Long COVID and its chronic fatigue syndrome as well as its affective symptoms.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.011}, pmid = {39522688}, issn = {2090-1224}, abstract = {INTRODUCTION: Autoimmune responses contribute to the pathophysiology of Long COVID, affective symptoms and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

OBJECTIVES: To examine whether Long COVID, and its accompanying affective symptoms and CFS are associated with immunoglobulin (Ig)A/IgM/IgG directed at neuronal proteins including myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), synapsin, α + β-tubulin, neurofilament protein (NFP), cerebellar protein-2 (CP2), and the blood-brain-barrier-brain-damage (BBD) proteins claudin-5 and S100B.

METHODS: IgA/IgM/IgG to the above neuronal proteins, human herpes virus-6 (HHV-6) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were measured in 90 Long COVID patients and 90 healthy controls, while C-reactive protein (CRP), and advanced oxidation protein products (AOPP) in association with affective and CFS ratings were additionally assessed in a subgroup thereof.

RESULTS: Long COVID is associated with significant increases in IgG directed at tubulin (IgG-tubulin), MBP, MOG and synapsin; IgM-MBP, MOG, CP2, synapsin and BBD; and IgA-CP2 and synapsin. IgM-SARS-CoV-2 and IgM-HHV-6 antibody titers were significantly correlated with IgA/IgG/IgM-tubulin and -CP2, IgG/IgM-BBD, IgM-MOG, IgA/IgM-NFP, and IgG/IgM-synapsin. Binary logistic regression analysis shows that IgM-MBP and IgG-MBP are the best predictors of Long COVID. Multiple regression analysis shows that IgG-MOG, CRP and AOPP explain together 41.7 % of the variance in the severity of CFS. Neural network analysis shows that IgM-synapsin, IgA-MBP, IgG-MOG, IgA-synapsin, IgA-CP2, IgG-MBP and CRP are the most important predictors of affective symptoms due to Long COVID with a predictive accuracy of r = 0.801.

CONCLUSION: Brain-targeted autoimmunity contributes significantly to the pathogenesis of Long COVID and the severity of its physio-affective phenome.}, } @article {pmid39521013, year = {2024}, author = {Alwan, NA and Al-Aly, Z}, title = {Learning from long COVID: conceptualising action to tackle infection-associated non-communicable diseases.}, journal = {Lancet (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1016/S0140-6736(24)02256-6}, pmid = {39521013}, issn = {1474-547X}, } @article {pmid39520983, year = {2024}, author = {Azhir, A and Hügel, J and Tian, J and Cheng, J and Bassett, IV and Bell, DS and Bernstam, EV and Farhat, MR and Henderson, DW and Lau, ES and Morris, M and Semenov, YR and Triant, VA and Visweswaran, S and Strasser, ZH and Klann, JG and Murphy, SN and Estiri, H}, title = {Precision phenotyping for curating research cohorts of patients with unexplained post-acute sequelae of COVID-19.}, journal = {Med (New York, N.Y.)}, volume = {}, number = {}, pages = {100532}, doi = {10.1016/j.medj.2024.10.009}, pmid = {39520983}, issn = {2666-6340}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; R01 AI165535/AI/NIAID NIH HHS/United States ; U24 TR004111/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews to tune and validate the algorithm.

FINDINGS: The PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying PASC cohorts compared to the ICD-10-CM code U09.9. The algorithm identified a cohort of over 24,000 patients with 79.9% precision. Our estimated prevalence of PASC was 22.8%, which is close to the national estimates for the region. We also provide in-depth analyses, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC.

CONCLUSIONS: PASC precision phenotyping boasts superior precision and prevalence estimation while exhibiting less bias in identifying patients with PASC. The cohort derived from this algorithm will serve as a springboard for delving into the genetic, metabolomic, and clinical intricacies of PASC, surmounting the constraints of prior PASC cohort studies.

FUNDING: This research was funded by the US National Institute of Allergy and Infectious Diseases (NIAID).}, } @article {pmid39520297, year = {2024}, author = {Carvajal, R and Rodríguez-Acevedo, B and García-Vasco, L and Zabalza, A and Ariño, H and Bollo, L and Cabello-Clotet, N and Castilló, J and Cobo-Calvo, Á and Comabella, M and Falcó-Roget, A and Galán, I and García-Sarreón, A and Gómez-Estévez, I and Granados, G and La Puma, D and Mato Chain, G and Midaglia, L and Nieto-García, A and Otero-Romero, S and Pappolla, A and Rodriguez, M and Sansano, I and Río, J and Tagliani, P and Tur, C and Vidal-Jordana, Á and Vilaseca, A and Villar, A and Sastre-Garriga, J and Oreja-Guevara, C and Tintoré, M and Montalban, X and Arrambide, G}, title = {Secondary organising pneumonia associated to COVID-19 infection in patients with central nervous system inflammatory demyelinating diseases treated with anti-CD20 therapies.}, journal = {Multiple sclerosis (Houndmills, Basingstoke, England)}, volume = {30}, number = {14}, pages = {1788-1801}, doi = {10.1177/13524585241297038}, pmid = {39520297}, issn = {1477-0970}, mesh = {Humans ; Female ; *COVID-19/complications/immunology ; Middle Aged ; Male ; *Rituximab/therapeutic use/adverse effects ; Retrospective Studies ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use ; *SARS-CoV-2 ; Immunologic Factors/therapeutic use ; Neuromyelitis Optica/drug therapy/immunology ; Multiple Sclerosis/drug therapy ; Pneumonia, Viral/complications/drug therapy/immunology ; Demyelinating Autoimmune Diseases, CNS/drug therapy/immunology ; Antigens, CD20/immunology ; Pandemics ; Coronavirus Infections/complications/drug therapy/immunology ; Organizing Pneumonia ; }, abstract = {BACKGROUND: Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited.

AIM: To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20.

METHODS: Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023.

RESULTS: Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID.

CONCLUSIONS: In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered.}, } @article {pmid39518964, year = {2024}, author = {Paranga, TG and Mitu, I and Pavel-Tanasa, M and Rosu, MF and Miftode, IL and Constantinescu, D and Obreja, M and Plesca, CE and Miftode, E}, title = {Cytokine Storm in COVID-19: Exploring IL-6 Signaling and Cytokine-Microbiome Interactions as Emerging Therapeutic Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, pmid = {39518964}, issn = {1422-0067}, support = {158/2022//Grigore T. Popa University of Medicine and Pharmacy of Iasi/ ; POC/448/1/1/127606 CENEMED project no. 367/390043/2021//Grigore T. Popa University of Medicine and Pharmacy of Iasi/ ; }, mesh = {Humans ; *COVID-19/immunology ; *Cytokine Release Syndrome/immunology/drug therapy ; *Interleukin-6/metabolism/immunology ; *Signal Transduction ; *SARS-CoV-2/immunology ; *Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; COVID-19 Drug Treatment ; }, abstract = {IL-6 remains a key molecule of the cytokine storms characterizing COVID-19, exerting both proinflammatory and anti-inflammatory effects. Emerging research underscores the significance of IL-6 trans-signaling over classical signaling pathways, which has shifted the focus of therapeutic strategies. Additionally, the synergistic action of TNF-α and IFN-γ has been found to induce inflammatory cell death through PANoptosis, further amplifying the severity of cytokine storms. Long COVID-19 patients, as well as those with cytokine storms triggered by other conditions, exhibit distinct laboratory profiles, indicating the need for targeted approaches to diagnosis and management. Growing evidence also highlights the gut microbiota's crucial role in modulating the immune response during COVID-19 by affecting cytokine production, adding further complexity to the disease's immunological landscape. Targeted intervention strategies should focus on specific cytokine cutoffs, though accurate cytokine quantification remains a clinical challenge. Current treatment strategies are increasingly focused on inhibiting IL-6 trans-signaling, which offers promise for more precise therapeutic approaches to manage hyperinflammatory responses in COVID-19. In light of recent discoveries, this review summarizes key research findings on cytokine storms, particularly their role in COVID-19 and other inflammatory conditions. It explores emerging therapeutic strategies targeting cytokines like IL-6, TNF-α, and IFN-γ, while also addressing open questions, such as the need for better biomarkers to detect and manage cytokine storms. Additionally, the review highlights ongoing challenges in developing targeted treatments that mitigate hyperinflammation without compromising immune function, emphasizing the importance of continued research in this field.}, } @article {pmid39518632, year = {2024}, author = {Pietranis, KA and Kostro, AM and Dzięcioł-Anikiej, Z and Moskal-Jasińska, D and Kuryliszyn-Moskal, A}, title = {Impact of COVID-19 on Diaphragmatic Function: Understanding Multiorgan Involvement and Long-Term Consequences.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518632}, issn = {2077-0383}, abstract = {The COVID-19 pandemic has brought significant attention to the respiratory system, with much focus on lung-related disorders. However, the diaphragm, a crucial component of respiratory physiology, has not been adequately studied, especially in the context of long COVID. This review explores the multipotential role of the diaphragm in both respiratory health and disease, emphasizing its involvement in long-term complications following SARS-CoV-2 infection. The diaphragm's fundamental role in respiratory physiology and its impact on balance and posture control, breathing patterns, and autonomic nervous system regulation are discussed. This review examines complications arising from COVID-19, highlighting the diaphragm's involvement in neurological, musculoskeletal, and inflammatory responses. Particular attention is given to the neuroinvasive impact of SARS-CoV-2, the inflammatory response, and the direct viral effects on the diaphragm. The diaphragm's role in long COVID is explored, with a focus on specific symptoms such as voice disorders, pelvic floor dysfunction, and sleep disturbances. Diagnostic challenges, current methods for assessing diaphragmatic dysfunction, and the complexities of differentiating it from other conditions are also explored. This article is the first to comprehensively address diaphragmatic dysfunction resulting from COVID-19 and long COVID across various physiological and pathological aspects, offering a new perspective on its diagnosis and treatment within a multisystem context.}, } @article {pmid39518437, year = {2024}, author = {Chero-Sandoval, L and Martínez-Urbistondo, M and Cuevas-Sierra, A and Higuera-Gómez, A and Martin-Domenech, E and Castejón, R and Mellor-Pita, S and Moreno-Torres, V and Ramos-Lopez, O and de Luis, D and Vargas, JA and Martínez, JA}, title = {Comparison of Metabolic Syndrome, Autoimmune and Viral Distinctive Inflammatory Related Conditions as Affected by Body Mass Index.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, pmid = {39518437}, issn = {2077-0383}, support = {Y2020/6600//Government of Madrid/ ; }, abstract = {Background: Metabolic inflammation (MI), long COVID (LC) and systemic lupus erythematosus (SLE) share some metabolic common manifestations and inflammatory pathophysiological similarities. Health-related quality of life (HRQoL) and metabolic age are indicators of health status. The "METAINFLAMMATION-CM Y2020/BIO-6600" project, a prospective controlled study, aimed to identify differential diagnostic tools and clinical features among three inflammatory conditions by comparing obesity status (low BMI vs. high BMI). Methods: A total of 272 adults of both Caucasian and Hispanic descent, diagnosed with MI, LC or SLE, and a range of BMI, were recruited. Clinical and phenotypic traits were measured to analyze body composition, metabolic and inflammatory markers, HRQoL data, metabolic age and lifestyle habits using a 3 × 2 (disease × BMI) factorial design. Results: Some inflammatory related variables, such as fibrinogen, RDW (red cell blood distribution width), ESR (erythrocyte sedimentation rate) and NLR (neutrophil/lymphocyte ratio), showed effect modifications depending on the BMI and disease type. In relation to HRQoL, the Physical Component Summary (PCS12) showed no relevant changes, while the Mental Component Summary (MCS12) showed a significant effect modification according to the disease type and BMI (p < 0.05). Furthermore, a significant interaction was identified between the disease type and BMI in relation to metabolic age (p = 0.02). Conclusions: Assessing the impact of BMI on these three inflammatory diseases may help to prevent clinical complications and to design personalized treatments, especially for patients with SLE, who have a worse prognosis with an increased BMI compared to the other two inflammatory diseases.}, } @article {pmid39516956, year = {2024}, author = {Berentschot, JC and Bek, LM and Heijenbrok-Kal, MH and van Bommel, J and Ribbers, GM and Aerts, JGJV and Hellemons, ME and van den Berg-Emons, HJG and , }, title = {Long-term health outcomes of COVID-19 in ICU- and non-ICU-treated patients up to 2 years after hospitalization: a longitudinal cohort study (CO-FLOW).}, journal = {Journal of intensive care}, volume = {12}, number = {1}, pages = {47}, pmid = {39516956}, issn = {2052-0492}, support = {10430022010026/ZONMW_/ZonMw/Netherlands ; }, abstract = {BACKGROUND: Many patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19.

METHODS: The CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected.

RESULTS: 650 patients (median age 60.0 [IQR 53.0-67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes.

CONCLUSIONS: 73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery.

TRIAL REGISTRATION: NL8710, registration date 12-06-2020.}, } @article {pmid39516880, year = {2024}, author = {Aiyegbusi, OL and McMullan, C and Hughes, SE and Turner, GM and Haroon, S and Hotham, R and Brown, K and Alder, Y and Agyen, L and Buckland, L and Camaradou, J and Chong, A and Jeyes, F and Matthews, KL and Moore, P and Ormerod, J and Price, G and Saint-Cricq, M and Stanton, D and Walker, A and Calvert, MJ}, title = {Implementation of patient and public involvement and engagement (PPIE) for the therapies for long COVID in non-hospitalised individuals (TLC) project.}, journal = {Research involvement and engagement}, volume = {10}, number = {1}, pages = {120}, pmid = {39516880}, issn = {2056-7529}, support = {COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//National Institute for Health and Care Research/ ; COV-LT-0013//National Institute for Health and Care Research/ ; }, abstract = {BACKGROUND: Patients, their family members and caregivers have firsthand experiences of living with or supporting someone living with a disease or medical condition. This knowledge by experience cannot be replaced by the knowledge acquired by clinicians, researchers, or other professionals through study and/or work. The Therapies for Long COVID in non-hospitalised individuals (TLC) research project was funded in the UK by the National Institute for Health and Care Research (NIHR) and UK Research and Innovation to investigate the impact of long COVID on affected individuals. This article focuses on the implementation of PPIE for the TLC project. It provides details on the methodological approach that was adopted, the evaluation and reporting of the PPIE for the project and some previously unreported challenges we faced.

MAIN BODY: A PPIE Lead was appointed to coordinate PPIE for the project and facilitate communication and relationship building with the patient partners. Our overarching approach was collaborative with patient partners actively involved in the various work packages of the project.. This was achieved by recruiting PPIE members from (1) direct contacts, (2) long COVID support groups (3) a local general practitioner (GP) surgery. Although we were unable to hold face-to-face meetings due to the social restrictions during the COVID-19 pandemic, we offered patients the choice of using virtual platforms like Zoom, telephone calls, and emails for communication. We adopted a 4-tiered model for the PPIE group with each tier providing different opportunities for contributing to the project. This model helped the PPIE Lead to effectively co-ordinate PPIE activities for the project as well as provide all patient partners the opportunity to contribute to the project whilst managing their condition. PPIE for the TLC project was co-evaluated with patient partners.

CONCLUSIONS: Despite the challenges we encountered with the pandemic, the TLC project provided a valuable opportunity for patients to shape the design, conduct and dissemination of the research findings. The information provided in this article may be useful to other researchers and patients when planning PPIE for future health research. The implementation of PPIE in healthcare research could help ensure that the outcomes of research are those valued by and relevant to the needs of patients and other end users.}, } @article {pmid39516528, year = {2024}, author = {Zulbaran-Rojas, A and Bara, RO and Lee, M and Bargas-Ochoa, M and Phan, T and Pacheco, M and Camargo, AF and Kazmi, SM and Rouzi, MD and Modi, D and Shaib, F and Najafi, B}, title = {Transcutaneous electrical nerve stimulation for fibromyalgia-like syndrome in patients with Long-COVID: a pilot randomized clinical trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {27224}, pmid = {39516528}, issn = {2045-2322}, mesh = {Humans ; *Transcutaneous Electric Nerve Stimulation/methods ; *Fibromyalgia/therapy ; Female ; Pilot Projects ; Middle Aged ; Male ; *COVID-19/complications/therapy ; Adult ; Fatigue/therapy/etiology ; Treatment Outcome ; Aged ; SARS-CoV-2 ; Gait ; }, abstract = {This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease in BPI-I compared to the PG (mean difference = 2.61, p = 0.008), and improved in gait parameters including stride time (4-8%, test condition dependent), cadence (4-10%, depending on condition), and double-support phase (12% in dual-task) when compared to baseline. A sub-group meeting the 2010 American College of Rheumatology Fibromyalgia diagnostic criteria undergoing high-dose TENS showed GFI improvement at 4-weeks from baseline (mean change = 6.08, p = 0.005). Daily TENS therapy showed potential in reducing functional interference from pain, fatigue, and gait alterations in long-COVID individuals. The study's limited power could affect the confirmation of certain observations. Extending the intervention period may improve treatment effectiveness.}, } @article {pmid39516425, year = {2025}, author = {Narayanan, SN and Padiyath, S and Chandrababu, K and Raj, L and P S, BC and Ninan, GA and Sivadasan, A and Jacobs, AR and Li, YW and Bhaskar, A}, title = {Neurological, psychological, psychosocial complications of long-COVID and their management.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {46}, number = {1}, pages = {1-23}, pmid = {39516425}, issn = {1590-3478}, mesh = {Humans ; *COVID-19/psychology/complications ; *Nervous System Diseases/etiology/psychology/therapy ; *Post-Acute COVID-19 Syndrome ; Mental Disorders/etiology/therapy/psychology ; SARS-CoV-2 ; }, abstract = {Since it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed 'long-COVID'. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms. A concise account of the clinical relevance of the neurological and psychosocial impacts of long-COVID, the effects on long-term morbidity, and varied approaches in managing patients with significant chronic neurological symptoms and conditions was extracted from the literature, analysed and reported. A comprehensive account of plausible pathophysiological mechanisms involved in the development of long-COVID, its management, and future research needs have been discussed.}, } @article {pmid39515869, year = {2024}, author = {Portela, MC and de Vasconcellos, MTL and Lima, SML and Caldas, BDN and Martins, M and de Andrade, CLT and Amaral, TLM and Amaral, CA and Bernardino, M and Soares, L and Stelson, E and Aveling, EL and Rosenthal, MB}, title = {Protocol for an ambidirectional cohort study on long COVID and the healthcare needs, use and barriers to access health services in a large city in Southeast Brazil.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e086656}, doi = {10.1136/bmjopen-2024-086656}, pmid = {39515869}, issn = {2044-6055}, mesh = {Humans ; Brazil/epidemiology ; *Health Services Accessibility ; *COVID-19/epidemiology/therapy ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Health Services Needs and Demand ; Research Design ; Adult ; Quality of Life ; Retrospective Studies ; Cohort Studies ; }, abstract = {INTRODUCTION: Post-COVID-19 condition, or syndrome, also known as long COVID, is an infection-associated chronic condition that can develop after a SARS-CoV-2 infection and last at least 3 months to years. Despite representing a high burden for the Unified Health System (SUS), which has affected millions of Brazilians, it has received limited attention in Brazil. Prevalence studies to date have failed to include a broad representation of the population, and there has been insufficient exploration of the impact on people's lives and the burden of and barriers to accessing health services. This article presents the research protocol for the quantitative component of a mixed methods project to produce evidence to inform SUS's provision of care for long COVID. The protocol was designed to study long COVID in SUS patients hospitalised for COVID-19 in a large city in Southeast Brazil to capture symptoms and factors associated with the syndrome, effects on quality of life and employment, health needs, use of health services and barriers to accessing necessary healthcare.

METHODS AND ANALYSIS: An ambidirectional cohort study to capture data retrospectively and prospectively from adults previously discharged from SUS hospitals for COVID-19. The study involves up to two telephone surveys with the patients or proxies selected from a sampling plan for population estimates. Survey questions include baseline and follow-up data on demographic, socioeconomic, comorbidities, work status, health-related quality of life, vaccination status, long COVID symptoms, healthcare needs, use and barriers to access. Descriptive and appropriate multivariable analyses will be employed.

ETHICS AND DISSEMINATION: The project was approved by the Research Ethics Committees of participant institutions and by the Brazilian National Research Ethics Commission. All participants provided verbal consent. We plan to publish articles in scientific journals and multimedia resources for SUS professionals and the general population.}, } @article {pmid39512484, year = {2024}, author = {Downer, MB and Tucker, E and Fraser, E and Pick, A}, title = {CHARACTERIZATION OF BASELINE SYMPTOMS AND FUNCTIONAL IMPAIRMENTS IN A LARGE COHORT OF OUTPATIENTS ATTENDING A LONG COVID REHABILITATION CLINIC IN THE UNITED KINGDOM.}, journal = {Journal of rehabilitation medicine. Clinical communications}, volume = {7}, number = {}, pages = {39984}, pmid = {39512484}, issn = {2003-0711}, abstract = {OBJECTIVE: In response to the high prevalence and morbidity associated with long COVID (LC), outpatient rehabilitation programmes were created across jurisdictions. We aimed to characterize baseline symptoms and impairments of patients attending outpatient LC rehabilitation.

DESIGN: This study was a retrospective quality-improvement analysis.

SUBJECTS/PATIENTS: Patients attending outpatient LC rehabilitation at the Oxfordshire Post-Covid Service.

METHODS: Data included age/sex and 6 questionnaires performed at baseline: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Dyspnoea-12 (D12), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Assessment-7 (GAD-7), Visual Analogue Scale (VAS) of self-rated health, and the Work And Social Adjustment Scale (WSAS). All scores were dichotomized (indicating presence/absence of clinically significant pathology). Potential differences between age (
RESULTS: A total of 422 patients were included (mean/standard deviation [SD] age = 47.1/13.2;132/31.3% male). A total of 76% had significant fatigue (FACIT-F), 69% had breathlessness (D12), 55% had depression (PHQ-9), 34% had anxiety (GAD-7), 41% self-reported poor health (VAS), and 57% had work/social life dysfunction (WSAS). D12 scores differed between age groups (older > younger, χ[2] = 3.19/p = 0.048), with no differences observed on other scales.

CONCLUSION: In this preliminary study, a high proportion of LC outpatients had significant impairments across domains. The findings of this study reaffirm the need for high-quality, multidisciplinary LC rehabilitation, and may be used to help build a standardized set of outcome measures moving forward.}, } @article {pmid39511637, year = {2024}, author = {Nugawela, MD and Stephenson, T and Shafran, R and Chalder, T and Dalrymple, E and Ford, T and Fox-Smith, L and Harnden, A and Heyman, I and Ladhani, SN and McOwat, K and Simmons, R and Swann, O and Whittaker, E and , and Pinto Pereira, SM}, title = {Predicting post-COVID-19 condition in children and young people up to 24 months after a positive SARS-CoV-2 PCR-test: the CLoCk study.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {520}, pmid = {39511637}, issn = {1741-7015}, support = {COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//National Institute for Health and Care Research/ ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/diagnosis ; Male ; Child ; Female ; Adolescent ; *SARS-CoV-2/genetics ; Child, Preschool ; COVID-19 Nucleic Acid Testing/methods ; Post-Acute COVID-19 Syndrome ; Young Adult ; Infant ; Risk Factors ; }, abstract = {BACKGROUND: Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP.

METHODS: CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting.

RESULTS: While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064-1.142; C-statistic: 0.724-0.755).

CONCLUSIONS: To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.}, } @article {pmid39511549, year = {2024}, author = {Wojczewski, S and Mayrhofer, M and Szabo, N and Rabady, S and Hoffmann, K}, title = {"A bit of a cough, tired, not very resilient - is that already Long-COVID?" perceptions and experiences of GPs with Long-COVID in year three of the pandemic. a qualitative interview study in Austria.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {3078}, pmid = {39511549}, issn = {1471-2458}, mesh = {Humans ; Austria/epidemiology ; *COVID-19/epidemiology ; *General Practitioners/psychology ; *Qualitative Research ; Male ; Female ; Middle Aged ; Adult ; *Interviews as Topic ; Attitude of Health Personnel ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Primary Health Care ; Pandemics ; Health Knowledge, Attitudes, Practice ; Aged ; }, abstract = {BACKGROUND: Long-COVID is a new multisectoral healthcare challenge. This study aims at understanding experiences, knowledge, attitudes and (information) needs that GPs had and have in relation to Long-COVID and how these evolved since the beginning of the COVID-19 pandemic.

METHODS: The study used an exploratory qualitative research design using semistructured interviews. A total of 30 semistructured interviews with GPs in different primary care settings (single practices, group practices, primary care centres) were conducted between February and July 2022. The data were analysed using qualitative thematic content analysis with the software Atlas.ti.

RESULTS: This is the first study that empirically investigated Long-COVID management by GPs in Austria during the third year of the pandemic. All GPs indicated having experience with Long-COVID. In cities, GPs tended to have slightly better networks with specialists. The GPs who already worked in teams tended to find the management of Long-COVID easier. The symptoms that the physicians described as Long-COVID symptoms corresponded to those described in the international literature, but it is unclear whether syndromes and symptomes such as Post-Exertional-Malaise, autonomic dysfunction such as postural tachycardia syndrome or Mast-Cell-Overactivation-Syndrom, and cognitive dysfunctions were also recognized and correctly classified since they were never mentioned. Most GPs reacted quickly by granting the needed sick leaves and by seeing and discussing with the patients often.The treatment of the patients is described as an enormous challenge and frustrating for patient and GP if the treatment does not yield to significantly improved health also due to the high costs for the patient.

CONCLUSION: Long-COVID will continue to preoccupy our health care systems for a long time to come, as new variants of COVID-19 will continue to produce new patients without adequate prevention strategies. Therefore, it is not a question of if but when good support for GPs and adequate care pathways for people with Long-COVID will be implemented. Specific contact points that are familiar with therapy-refractory postacute infection syndromes like the postacute COVID condition as a subgroup of Long-COVID are urgently needed.}, } @article {pmid39511082, year = {2024}, author = {Diener, HC}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {19}, pages = {27}, doi = {10.1007/s15006-024-4439-5}, pmid = {39511082}, issn = {1613-3560}, } @article {pmid39510798, year = {2024}, author = {Christ, W and Kapell, S and Sobkowiak, MJ and Mermelekas, G and Evertsson, B and Sork, H and Saher, O and Bazaz, S and Gustafsson, O and Cardenas, EI and Villa, V and Ricciarelli, R and Sandberg, JK and Bergquist, J and Sturchio, A and Svenningsson, P and Malm, T and Espay, AJ and Pernemalm, M and Lindén, A and Klingström, J and El Andaloussi, S and Ezzat, K}, title = {SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion.}, journal = {ACS chemical neuroscience}, volume = {15}, number = {22}, pages = {4095-4104}, doi = {10.1021/acschemneuro.4c00636}, pmid = {39510798}, issn = {1948-7193}, mesh = {Humans ; *Herpesvirus 1, Human ; *SARS-CoV-2 ; *COVID-19 ; Amyloid/metabolism ; Protein Aggregates/physiology ; }, abstract = {The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as APLP1 (amyloid β precursor like protein 1), ApoE, clusterin, α2-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin, and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Additionally, viral amyloid induction led to a dramatic drop in the soluble protein concentration in the CSF. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF and result in soluble protein depletion, thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.}, } @article {pmid39510792, year = {2024}, author = {Kim, C and Lin, C and Wong, M and Al Hamour Al Jarad, S and Gao, A and Kaufman, N and McDuff, K and Brown, DA and Cobbing, S and Minor, A and Chan Carusone, S and O'Brien, KK}, title = {Experiences of physiotherapists working with adults living with Long COVID in Canada: a qualitative study.}, journal = {BMJ open}, volume = {14}, number = {11}, pages = {e086357}, pmid = {39510792}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Physical Therapists ; *Qualitative Research ; Male ; Cross-Sectional Studies ; Canada ; Adult ; SARS-CoV-2 ; Middle Aged ; Attitude of Health Personnel ; Health Knowledge, Attitudes, Practice ; }, abstract = {OBJECTIVES: To explore experiences of physiotherapists working with adults living with Long COVID in Canada.

DESIGN: Cross-sectional descriptive qualitative study involving online semi-structured interviews.

PARTICIPANTS: We recruited physiotherapists in Canada who self-identified as having clinically treated one or more adults living with Long COVID in the past year.

DATA COLLECTION: Using an interview guide, we inquired about physiotherapists' knowledge of Long COVID, assessment and treatment experiences, perspectives on physiotherapists' roles, contextual and implementation factors influencing rehabilitative outcomes, and their recommendations for Long COVID rehabilitation. Interviews were audio-recorded, transcribed verbatim and analysed using a group-based thematic analytical approach. We administered a demographic questionnaire to describe sample characteristics.

RESULTS: 13 physiotherapists from five provinces participated; most were women (n=8; 62%) and practised in urban settings (n=11; 85%). Participants reported variable amounts of knowledge of existing guidelines and experiences working with adults living with Long COVID in the past year. Physiotherapists characterised their experiences working with adults living with Long COVID as a dynamic process involving: (1) a disruption to the profession (encountering a new patient population and pivoting to new models of care delivery), followed by (2) a cyclical process of learning curves and evolving roles of physiotherapists working with persons living with Long COVID (navigating uncertainty, keeping up with rapidly emerging evidence, trial and error, adapting mindset and rehabilitative approaches and growing prominence of roles as advocate and collaborator). Participants recommended the need for education and training, active and open-minded listening with patients, interdisciplinary models of care, and organisational- and system-level improvements to foster access to care.

CONCLUSIONS: Physiotherapists' experiences involved a disruption to the profession followed by a dynamic process of learning curves and evolving roles in Long COVID rehabilitation. Not all participants demonstrated an in-depth understanding of existing Long COVID rehabilitation guidelines. Results may help inform physiotherapy education in Long COVID rehabilitation.}, } @article {pmid39510073, year = {2024}, author = {Ouonkap, SVY and Palaniappan, M and Pryze, K and Jong, E and Foteh Ali, M and Styler, B and Althiab Almasaud, R and Harkey, AF and Reid, RW and Loraine, AE and Smith, SE and Pease, JB and Muday, GK and Palanivelu, R and Johnson, MA}, title = {Enhanced pollen tube performance at high temperature contributes to thermotolerant fruit and seed production in tomato.}, journal = {Current biology : CB}, volume = {34}, number = {22}, pages = {5319-5333.e5}, pmid = {39510073}, issn = {1879-0445}, support = {P01 CA095616/CA/NCI NIH HHS/United States ; R35 GM139609/GM/NIGMS NIH HHS/United States ; }, mesh = {*Solanum lycopersicum/growth & development/physiology ; *Pollen Tube/growth & development/physiology ; *Thermotolerance ; *Fruit/growth & development ; *Seeds/growth & development/physiology ; *Hot Temperature ; }, abstract = {Rising temperature extremes during critical reproductive periods threaten the yield of major grain and fruit crops. Flowering plant reproduction depends on the ability of pollen grains to generate a pollen tube, which elongates through the pistil to deliver sperm cells to female gametes for double fertilization. We used tomato as a model fruit crop to determine how high temperature affects the pollen tube growth phase, taking advantage of cultivars noted for fruit production in exceptionally hot growing seasons. We found that exposure to high temperature solely during the pollen tube growth phase limits fruit biomass and seed set more significantly in thermosensitive cultivars than in thermotolerant cultivars. Importantly, we found that pollen tubes from the thermotolerant Tamaulipas cultivar have enhanced growth in vivo and in vitro under high temperature. Analysis of the pollen tube transcriptome's response to high temperature allowed us to define two response modes (enhanced induction of stress responses and higher basal levels of growth pathways repressed by heat stress) associated with reproductive thermotolerance. Importantly, we define key components of the pollen tube stress response, identifying enhanced reactive oxygen species (ROS) homeostasis and pollen tube callose synthesis and deposition as important components of reproductive thermotolerance in Tamaulipas. Our work identifies the pollen tube growth phase as a viable target to enhance reproductive thermotolerance and delineates key pathways that are altered in crop varieties capable of fruiting under high-temperature conditions.}, } @article {pmid39508631, year = {2024}, author = {Roshanzamir, Z and Mohammadi, F and Yadegar, A and Naeini, AM and Hojabri, K and Shirzadi, R}, title = {An Overview of Pediatric Pulmonary Complications During COVID-19 Pandemic: A Lesson for Future.}, journal = {Immunity, inflammation and disease}, volume = {12}, number = {11}, pages = {e70049}, pmid = {39508631}, issn = {2050-4527}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications/prevention & control ; Child ; *SARS-CoV-2 ; Pandemics ; Child, Preschool ; Respiratory Distress Syndrome/etiology/epidemiology ; }, abstract = {BACKGROUND: The pediatric community is considered a suitable target for controlling the spread and mortality of viral diseases. In late December 2019, a respiratory disease due to the novel coronavirus, later COVID-19, hit the globe. The COVID-19 global disruption had direct and indirect impacts on different aspects of child health. Therefore, surveillance, preventive approaches, and treatment plans for children came into the spotlight.

OBJECTIVE: This study aims to discuss the clinical pictures as well as laboratory and radiological findings of the infected children during the COVID-19 pandemic. The focus of this study is to express the clinical manifestations of respiratory disease in pediatric SARS-CoV-2, available therapeutic options, vaccine recommendations, and long COVID sequelae in affected children. This review could serve as a hint for upcoming challenges in pediatric care during future pandemics.

RESULTS: The clinical presentation of COVID-19 in pediatrics can range from mild pulmonary disease to acute respiratory distress syndrome (ARDS). Supportive care is a crucial component of the management of pediatric COVID-19. However, the importance of specializing in how to treat patients with more severe conditions cannot be overstated. Additionally, clinicians must consider prevention strategies as well as potential complications.

CONCLUSION: Although the infected patients are dipping day by day, there is a lack of clinical guidelines for pediatric SARS-CoV-2-associated pulmonary diseases. Understanding of the physicians about all aspects of pediatric care during the COVID-19 pandemic could lead to enhanced quality of future patient care and safety, reduced costs of health policies, and surveil the risk that patients with respiratory viruses can expose to society.}, } @article {pmid39507661, year = {2024}, author = {Westermeier, F and Sepúlveda, N}, title = {Editorial: On the cusp of the silent wave of the long COVID pandemic: why, what and how should we tackle this emerging syndrome in the clinic and population?.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1483693}, pmid = {39507661}, issn = {2296-2565}, } @article {pmid39507365, year = {2024}, author = {Porter, CK and Beckett, CG and Cooper, E and White, L and Wallace, D and Jakubski, S and Boulifard, D and Schilling, M and Sun, P and Marayag, J and Marrone, A and Nunez-Hernandez, EO and Vangeti, S and Miller, C and Ge, Y and Ramos, I and Goforth, C and Sealfon, SC and Letizia, AG}, title = {Clinical and functional assessment of SARS-CoV-2 sequelae among young marines - a panel study.}, journal = {Lancet regional health. Americas}, volume = {39}, number = {}, pages = {100909}, pmid = {39507365}, issn = {2667-193X}, abstract = {BACKGROUND: Long-term SARS-CoV-2 adverse health outcomes are of significant concern, especially among young adults with the potential for the greatest long-term morbidity. We sought to assess and characterize these outcomes in a cohort of Marines.

METHODS: We used a cohort of US Marines from a previous longitudinal, prospective observational study of acute SARS-CoV-2, most of whom were enrolled prior to infection. A panel study was established to assess for post-acute sequelae of COVID-19 (PASC), defined as symptoms at least 4 weeks after symptom onset or diagnosis. Symptoms were assessed through questionnaires and validated quality of health metrics. Periodic US Marine Corps fitness testing metrics provided an additional standardized functional assessment and were compared to a pre-pandemic cohort.

FINDINGS: Globally dispersed Marine participants (n = 899) seen an average of 330 days following initial enrollment were predominately male (n = 825, 91.7%), White (n = 613, 71.6%) or Black (n = 149, 17.4%) with a median age of 18 years (interquartile range: 18-19). Among 798 SARS-CoV-2 infected participants, 197 (24.7%) developed PASC. The most prevalent symptoms were loss of taste and/or smell (n = 82; 41.6%), shortness of breath (n = 74; 37.6%), and cough (n = 45; 22.8%). Those with PASC had higher rates and severity of somatic (p < 0.0001), general depressive (p < 0.0001), and anxiety (p = 0.005) symptoms. Compared to a historic cohort of Marines, participants with PASC scored worse on their physical fitness assessments due to slower run times (p = 0.002). Those with PASC continued to have decreased physical performance one year after completing initial training.

INTERPRETATION: In this population of healthy young adult US Marines with mostly either asymptomatic or mild acute COVID-19, one fourth reported physical, cognitive, or psychiatric long-term sequelae of infection. The Marines affected with PASC showed evidence of long-term decrease in functional performance suggesting that SARS-CoV-2 infection may negatively affect health for a significant proportion of young adults.

FUNDING: Defense Health Agency and Defense Advanced Research Projects Agency.}, } @article {pmid39507087, year = {2024}, author = {Sirotiak, Z and Lee, DC and Brellenthin, AG}, title = {Associations between physical activity, long COVID symptom intensity, and perceived health among individuals with long COVID.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1498900}, pmid = {39507087}, issn = {1664-1078}, abstract = {INTRODUCTION: Physical activity (PA) is associated with better perceived health among individuals with chronic conditions. However, PA's relationship with perceived health in people with long COVID is unclear and may be modified by long COVID symptom burden.

METHODS: Participants with self-reported long COVID (N = 379) responded to an online survey cross-sectionally assessing PA levels, perceived physical and mental health, and intensity of CDC-defined long COVID symptoms on a 0-100 scale. Linear regression analyses assessed the associations between PA and perceived physical and mental health, after accounting for sociodemographic, health behavior, and long COVID intensity variables, with post-hoc analyses comparing health across PA levels.

RESULTS: Increasing levels of PA were associated with increases in perceived physical health (β = 0.27, p < 0.001) and mental health (β = 0.19, p < 0.001) after accounting for sociodemographic and health behavior variables. PA remained significantly associated with perceived physical health (β = 0.15, p < 0.001) but not perceived mental health (β = 0.09, p = 0.067) after the adding long COVID intensity to the model. Insufficiently active and active groups reported significant better physical and mental health than the inactive group (ps < 0.05), while the highly active group did not significantly differ from any other group on perceived physical or mental health (ps > 0.05). Inactive individuals reported significantly greater long COVID symptom burden compared to each other PA level (ps < 0.05).

CONCLUSION: Higher levels of PA may be associated with better physical health among individuals with long COVID, even after accounting for symptom intensity. However, long COVID symptom intensity may confound the relationship between PA and mental health among individuals with long COVID.}, } @article {pmid39506902, year = {2024}, author = {Skonieczny, G and Skowrońska, M and Dolacińska, A and Ratajczak, B and Sulik, P and Doroba, O and Kotula, A and Błażejowska, E and Staniszewska, I and Domaszk, O and Pruszczyk, P}, title = {Cardiovascular sequelae in symptomatic SARS-CoV-2 infection survivors.}, journal = {Cardiology journal}, volume = {}, number = {}, pages = {}, doi = {10.5603/cj.99538}, pmid = {39506902}, issn = {1898-018X}, abstract = {BACKGROUND: SARS-CoV-2 infection may lead to myocardial and endothelial damage. The present study sought to characterize the cardiovascular sequel in a large group of consecutive patients admitted for out-patient cardiovascular follow-up after a symptomatic COVID-19 infection.

METHODS: The aims of this study were as follows: to evaluate the presence of post-covid cardiovascular symptoms in an unselected population of outpatients referred to a post-COVID outpatient cardiology clinic and to characterize the long-term abnormalities associated with a more severe COVID-19 infection clinical course. A total of 914 patients were included in this single-center, observational, cross-sectional study, of which 163 were hospitalized and 149 required mechanical ventilation for COVID-19 pneumonia. Patients were analyzed at follow-up according to the care setting during the initial presentation.

RESULTS: The median time to follow-up was 126 days. At that time, only 3.5% of patients reported no persistent dyspnea, chest pain, or fatigue on exertion. In a follow-up echocardiographic assessment, patients who required hospitalization showed slight alterations in the pulmonary acceleration time and the tricuspid regurgitation pressure gradient, as well as reduced exercise tolerance during treadmill exercise testing when compared to patients with a benign clinical course. 24-hour Holter EKG monitoring or 24-hour blood pressure monitoring did not identify significant differences between the analyzed subgroups.

CONCLUSIONS: The current study reports on an association between COVID-19 severity and the presence of cardiovascular alterations at follow-up. A simple diagnostic protocol, comprising an exercise treadmill test and transthoracic echocardiography is useful in identifying patients who may benefit from regular, structured cardiovascular medical care.}, } @article {pmid39504683, year = {2025}, author = {Kim, SA and Maeda, M and Murata, F and Fukuda, H}, title = {Effect of COVID-19 vaccination on the risk of developing post-COVID conditions: The VENUS study.}, journal = {Vaccine}, volume = {43}, number = {Pt 2}, pages = {126497}, doi = {10.1016/j.vaccine.2024.126497}, pmid = {39504683}, issn = {1873-2518}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Male ; Female ; Retrospective Studies ; Japan/epidemiology ; Middle Aged ; *COVID-19 Vaccines/administration & dosage/immunology ; Incidence ; *SARS-CoV-2/immunology ; Aged ; *Vaccination ; Adult ; Post-Acute COVID-19 Syndrome ; Proportional Hazards Models ; Risk Factors ; }, abstract = {INTRODUCTION: Post-COVID-19 conditions have emerged as a global health challenge. This study examined the long-term effects of COVID-19 vaccination on the incidence and risk of post-COVID-19 conditions in Japan.

METHODS: This retrospective cohort study was conducted using a database comprising medical claims, COVID-19 case information, and vaccination records of persons residing in four Japanese municipalities. The cohort included COVID-19 cases diagnosed between August 2020 and December 2022. Participants were classified according to the duration between their most recent COVID-19 vaccination and COVID-19 occurrence (≥365 days, 150-364 days, and 14-149 days). The incidences of 36 post-COVID-19 conditions were monitored for 3, 5, and 8 months after infection. Cox proportional hazards models were used to calculate the risk of developing each post-COVID-19 condition within 8 months after infection according to vaccination status.

RESULTS: From among 84,464 participants, 9642 (11.4 %) developed post-COVID-19 conditions over 8 months. The 8-month risks of developing 28 (including various respiratory conditions, cardiovascular conditions, inflammatory and immune diseases, physical conditions, psychiatric conditions, and endocrine disorders) of the 36 target conditions were significantly lower when individuals had been recently vaccinated (14-149 days) before infection.

CONCLUSIONS: COVID-19 vaccination can reduce the incidence and risk of post-COVID-19 conditions if administered within 5 months before infection. Despite having the highest mean age and prevalence of comorbidities, individuals who were most recently vaccinated had a lower risk of developing post-COVID-19 conditions. These results provide important evidence for future COVID-19 vaccination strategies.}, } @article {pmid39500939, year = {2024}, author = {Baraniuk, JN and Thapaliya, K and Inderyas, M and Shan, ZY and Barnden, LR}, title = {Stroop task and practice effects demonstrate cognitive dysfunction in long COVID and myalgic encephalomyelitis / chronic fatigue syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26796}, pmid = {39500939}, issn = {2045-2322}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology/virology/physiopathology ; Female ; Male ; *COVID-19/psychology/complications ; *Stroop Test ; Adult ; *Cognitive Dysfunction/physiopathology ; Middle Aged ; *Reaction Time/physiology ; SARS-CoV-2 ; Cognition/physiology ; Case-Control Studies ; }, abstract = {BACKGROUND: The Stroop task was used to investigate differences in cognitive function between Long COVID (LC), Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and healthy control subjects.

METHODS: Subjects viewed four color words or neutral (XXXX) stimuli with the same (congruent) or different color ink (incongruent). Cognitive conflict was inferred from response times for pairings of prestimuli and subsequent stimuli. Overall effects were assessed by univariate analysis with time courses determined for binned response times.

RESULTS: LC and ME/CFS had significantly longer response times than controls indicating cognitive dysfunction. Initial response times were ranked LC > ME > HC, and decreased according to power functions. At the end of the task (900s), times were ranked LC = ME > HC. Response times were significantly slower for stimuli following an incongruent prestimulus. Time series for Stroop effect, facilitation, interference, surprise index and practice power law parameters were generally similar in LC, ME/CFS and HC suggesting comparable patterns for recruitment of cognitive resources. The prestimulus data were analyzed and generated positive Stroop and interference effects that were distinct from stimulus effects.

CONCLUSION: LC and ME/CFS have global slowing of response times that cannot be overcome by practice suggesting impaired communications between network nodes during problem solving. Analysis of matched prestimulus - stimulus effects adds a new dimension for understanding cognitive conflict.

BRIEF SUMMARY: Cognitive dysfunction in Long COVID and ME/CFS was demonstrated using the Stroop task which found global slowing of response times and limitations of practice effects.}, } @article {pmid39500905, year = {2024}, author = {Yelin, D and Ghantous, N and Awwad, M and Daitch, V and Kalfon, T and Mor, M and Buchrits, S and Shafir, Y and Shapira-Lichter, I and Leibovici, L and Yahav, D and Margalit, I and Shitenberg, D}, title = {Pulmonary diffusing capacity among individuals recovering from mild to moderate COVID-19: a cross-sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26767}, pmid = {39500905}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; *Pulmonary Diffusing Capacity ; Adult ; Dyspnea/physiopathology ; SARS-CoV-2/isolation & purification ; Severity of Illness Index ; Respiratory Function Tests ; Lung/physiopathology ; Aged ; }, abstract = {Impaired pulmonary diffusing capacity for carbon monoxide (DLCO) following COVID-19 has been consistently reported among individuals recovering from severe-critical infection. However, most long COVID cases follow non-severe COVID-19. We assessed DLCO among individuals with long COVID recovering from mild to moderate acute illness. A cross-sectional study of adults with long COVID, assessed at a COVID recovery clinic > 3 months following the onset of acute infection, during 2020-2021. Participants subjectively ranked their dyspnea severity based on its impact on their daily living and underwent comprehensive pulmonary function testing (PFT). Clinical correlates for impaired DLCO (defined as < 80%) were assessed using multivariable logistic regression models. A total of 458 individuals, their mean age 45 (SD 16) and 246 (54%) of whom are women, were evaluated at an average of ~ 4 months following acute COVID-19. The most frequent PFT impairment was reduced DLCO, identified among 67 (17%) of the cohort. Clinical correlates of impaired DLCO included women (odds ration [OR] 3.64, 95% confidence interval [CI] 1.78-7.45, p < 0.001), cigarette smoking (OR 2.25, 95% CI 1.14-4.43, p = 0.019), and moderate-severe dyspnea (OR 2.77, 95% CI 1.39-5.50, p = 0.004). BMI inversely correlated with DLCO (OR 0.90, 95% CI 0.85-0.96 per 1 unit, p = 0.002). Impaired DLCO was not uncommon among individuals recovering from mild to moderate COVID-19. Women are at a greater risk, and subjective dyspnea correlated with impaired DLCO. Clinicians can rely on self-reported significant dyspnea to guide further assessment.}, } @article {pmid39500417, year = {2025}, author = {Bremner, JD and Russo, SJ and Gallagher, R and Simon, NM}, title = {Acute and long-term effects of COVID-19 on brain and mental health: A narrative review.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {928-945}, doi = {10.1016/j.bbi.2024.11.007}, pmid = {39500417}, issn = {1090-2139}, mesh = {Humans ; *COVID-19/psychology/complications ; *Brain/diagnostic imaging ; *Mental Health ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Anxiety ; Anosmia/etiology/physiopathology ; Depression/psychology ; Fatigue/etiology/psychology ; Cognitive Dysfunction/etiology/physiopathology/psychology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome.

METHODS: This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression.

RESULTS: Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas.

CONCLUSIONS: Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.}, } @article {pmid39499751, year = {2024}, author = {Li, S and Sun, XC and Wu, ZF and Hu, L and Wang, JJ and Yin, M and Cheng, L and Wang, DH}, title = {Nasal irrigation for the prevention and treatment of upper respiratory tract infection by SARS-CoV-2: a narrative review.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {9.1}, pages = {S81-S91}, doi = {10.3855/jidc.19234}, pmid = {39499751}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/prevention & control/therapy ; *Nasal Lavage/methods ; *SARS-CoV-2 ; *Respiratory Tract Infections/prevention & control/virology/therapy ; }, abstract = {INTRODUCTION: The World Health Organization declared an end to the global emergency status of COVID-19 in May of 2023. However, the impact of COVID-19 is far from over. Individuals who have recovered from COVID-19 continue to experience physiological, psychological, or cognitive symptoms, such as fatigue, shortness of breath, dizziness, and loss of smell or taste, known as long COVID. This review aims to describe the clinical characteristics of the upper respiratory tract infection (URTI) caused by SARS-CoV-2, and provide evidence for the prevention and treatment of SARS-CoV-2 infection by using nasal irrigation. COVID-19 and nasal irrigation: Nasal irrigation presents a promising adjunct to standard COVID-19 prevention and treatment protocols. This practice is theorized to diminish viral presence in the upper respiratory tract, a region identified as a primary site for SARS-CoV-2 replication and shedding. By facilitating the removal of viral particles and enhancing mucociliary clearance, nasal irrigation could potentially lessen the severity of URTI symptoms and slow transmission rates. The review consolidates current evidence of the efficacy and safety of this approach across various populations, underscoring its practicality in both preventive and therapeutic contexts.

CONCLUSIONS: We recommend that saline nasal irrigation is an effective, safe and convenient strategy to prevent the transmission of SARS-CoV-2 and alleviate the symptoms of URTI across various age groups.}, } @article {pmid39499692, year = {2024}, author = {Gagnon, C and Vincent, T and Bherer, L and Gayda, M and Cloutier, SO and Nozza, A and Guertin, MC and Blaise, P and Cloutier, I and Kamada, A and Glezer, S and Denault, A and Tardif, JC}, title = {Oxygen supplementation and cognitive function in long-COVID.}, journal = {PloS one}, volume = {19}, number = {11}, pages = {e0312735}, pmid = {39499692}, issn = {1932-6203}, mesh = {Humans ; Male ; Female ; *Cognition ; Middle Aged ; *COVID-19/psychology ; *Cross-Over Studies ; Oxygen/metabolism ; Pilot Projects ; Aged ; Oxygen Saturation ; Oxygen Inhalation Therapy/methods ; SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Patients can experience persistent cognitive complaints and deficits in long-COVID. Inflammation and capillary damage may contribute to symptoms by interfering with tissue oxygenation.

METHODS: This was an exploratory pilot crossover study designed to describe the effects of supplemental oxygen (portable oxygen concentrator, POC) on cognitive performance and peripheral and cerebral oxygen saturation at rest and exercise. Participants with long-COVID (n = 21) were randomized 1:1 to: 1) POC (3h/day) for 2 weeks followed by standard of care (Control) for 2 weeks or 2) Control for 2 weeks then POC (3h/day) for 2 weeks, with a 1-week washout. Cognitive assessment (global cognition [Montreal Cognitive Assessment, MoCA], episodic memory [Hopkins], working memory [Digit Span], executive function [Verbal fluency]) was performed at baseline and after each treatment period. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 were completed. Peripheral and cerebral oxygen saturation were measured at rest and exercise (treadmill) at baseline and after each treatment period. Statistical analyses were descriptive without formal testing.

RESULTS: MoCA scores were similar under POC (26.45±2.31) and Control (26.37±2.85); overall POC-Control difference was -0.090 (95% CI [-1.031, 0.850]). Because of a learning effect, post-hoc analyses were performed for Period 1, where the MoCA score difference was 1.705 [0.140, 3.271]. MoCA subscores suggested better performance with POC for Visuospatial/executive (0.618 [-0.106, 1.342]) and Attention (0.975 [0.207, 1.743]). POC trended to have better scores on Digit Span backward (difference: 0.822 [-0.067, 1.711]) and self-reported depressive symptoms (difference: -1.335 [-3.166, 0.495]). For specific PHQ-9 items, POC tended to have lower (better) scores for Q1 (Little interest/pleasure) and Q7 (Trouble concentrating). Cerebral oxygen saturations at end of exercise showed no difference between POC and Control. Peripheral saturations during exercise were similar under POC and Control (difference: 0.519% [-1.675, 2.714]).

CONCLUSION: An advantage of POC over Control was observed for global cognition, attention, visuospatial/executive performance and depressive symptoms. Results need to be validated in a larger study.}, } @article {pmid39498382, year = {2024}, author = {Shen, XL and Jiang, YH and Li, SJ and Xie, XY and Cheng, Y and Wu, L and Shen, J and Chen, W and Liu, JR}, title = {Clinical features and predictive nomogram for fatigue sequelae in non-severe patients infected with SARS-CoV-2 Omicron variant in Shanghai, China.}, journal = {Brain, behavior, & immunity - health}, volume = {42}, number = {}, pages = {100889}, pmid = {39498382}, issn = {2666-3546}, abstract = {BACKGROUND: Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking.

OBJECTIVE: To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms.

METHODS: 223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue.

RESULTS: A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (n = 37,16.6%), cough (n = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56[+] cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae.

CONCLUSION: Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56[+] NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.}, } @article {pmid39497750, year = {2024}, author = {Lionaki, S and Dounousi, E and Marinaki, S and Kantartzi, K and Papasotiriou, M and Galitsiou, D and Bellos, I and Sardeli, A and Kalogeropoulos, P and Liakopoulos, V and Mpintas, C and Goumenos, D and Flouda, S and Venetsanopoulou, A and Voulgari, P and Andronikidi, E and Moustakas, G and Panagoutsos, S and Boletis, I}, title = {The clinical course of SARS-CoV-2 infection in patients with glomerular diseases and evaluation of the subsequent risk of relapse.}, journal = {Frontiers in nephrology}, volume = {4}, number = {}, pages = {1472294}, pmid = {39497750}, issn = {2813-0626}, abstract = {INTRODUCTION: This study aimed to describe the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with glomerular diseases (GDs) and its impact on the probability of relapse.

METHODS: Patients with biopsy-proven GD and positive PCR test for SARS-CoV-2 from glomerular clinics across Greece were studied retrospectively. Those who received the GD diagnosis after the SARS-CoV-2 vaccination or coronavirus disease 2019 (COVID-19) or ended in ESKD prior to infection were excluded. Demographics, histopathological diagnoses, past medical history, immunosuppression, and GD activity status were recorded.

RESULTS: A total of 219 patients with GDs and documented SARS-CoV-2 infection were included. The mean time from the diagnostic kidney biopsy to SARS-CoV-2 infection was 67.6 (± 59.3) months. Among the participants, 82.5% had been vaccinated against SARS-CoV-2 with three doses (range: 2.5-3) without subsequent GD reactivation in 96.2% of them. Twenty-two patients (10%) were hospitalized for COVID-19 and one (0.5%) required mechanical ventilation. Four (1.8%) died due to COVID-19 and one (0.5%) had long COVID-19 symptoms. Among patients in remission prior to SARS-CoV-2 infection, 22 (11.2%) experienced a GD relapse within 2.2 (range: 1.5-3.7) months from the diagnostic test. The relapse-free survival after COVID-19 was significantly shorter for patients with minimal change disease, pauci-immune glomerulonephritis, and focal segmental glomerulosclerosis. No difference was observed in the relapse-free survival post-COVID-19 based on the history of SARS-CoV-2 vaccination.

CONCLUSIONS: SARS-CoV-2 infection appears to have a symptomatic but uncomplicated sequence in vaccinated patients with GDs, with a significant impact on the clinical course of GD, associated with an increased probability of relapse in certain histopathological types.}, } @article {pmid39497519, year = {2024}, author = {Wang, H and Wei, Y and Lin, G and Boyer, C and Jia, KM and Hung, CT and Jiang, X and Li, C and Yam, CHK and Chow, TY and Wang, Y and Zhao, S and Guo, Z and Li, K and Yang, A and Mok, CKP and Hui, DSC and Chong, KC and Yeoh, EK}, title = {COVID-19 vaccination modified the effect of nirmatrelvir-ritonavir on post-acute mortality and rehospitalization: a retrospective cohort study.}, journal = {Emerging microbes & infections}, volume = {13}, number = {1}, pages = {2421397}, pmid = {39497519}, issn = {2222-1751}, mesh = {Humans ; *Ritonavir/therapeutic use/administration & dosage ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *COVID-19/prevention & control/mortality ; *SARS-CoV-2/immunology ; *Antiviral Agents/therapeutic use ; COVID-19 Vaccines/administration & dosage/immunology ; Vaccination ; Adult ; Hong Kong/epidemiology ; Drug Combinations ; Lopinavir/therapeutic use/administration & dosage ; Hospitalization/statistics & numerical data ; Patient Readmission/statistics & numerical data ; Aged, 80 and over ; }, abstract = {While previous research examined coronavirus disease 2019 (COVID-19) antiviral-vaccine interactions through exploratory subgroup analysis, none specifically designed for examining this interaction or its impact on post-acute outcomes. This study examined the interaction between nirmatrelvir-ritonavir and complete COVID-19 vaccination on reducing the risk of post-acute outcomes among COVID-19 patients. We followed COVID-19 patients hospitalized between 11 March 2022 and 10 October 2023, until 31 October 2023 in Hong Kong. Exposure groups were based on nirmatrelvir-ritonavir usage and vaccination status (fully or not fully vaccinated). Post-acute death and all-cause rehospitalization were the study outcomes. Propensity score weighting was applied to balance covariates among exposure groups, including age, sex, Charlson Comorbidity Index, and concomitant treatments. Multiplicative and additive interactions between nirmatrelvir-ritonavir and vaccination status were assessed. A total of 50,438 COVID-19 patients were included in this study and arranged into four exposure groups. Significant additive interaction on post-acute rehospitalization was observed (relative excess risk, 0.10; 95% CI, 0.02-0.19; p-value, 0.018; attributable proportion, 0.07; 95% CI, 0.01-0.12; p-value, 0.017; synergy index, 1.26; 95% CI, 1.02-1.55; p-value, 0.032). The interaction on post-acute mortality was marginally significant. In the subgroup analysis, the interaction effect is more pronounced in older adults, female, and CoronaVac recipients. In conclusion, our study demonstrated an additive interaction between nirmatrelvir-ritonavir and complete vaccination on post-acute outcomes, suggesting greater long-term benefits of the antiviral for fully vaccinated individuals compared to not fully vaccinated patients.}, } @article {pmid39497076, year = {2024}, author = {Szewczyk, W and Fitzpatrick, AL and Fossou, H and Gentile, NL and Sotoodehnia, N and Vora, SB and West, TE and Bertolli, J and Cope, JR and Lin, JS and Unger, ER and Vu, QM}, title = {Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1241}, pmid = {39497076}, issn = {1471-2334}, support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; *Quality of Life ; Female ; Male ; Middle Aged ; *Cognitive Dysfunction/epidemiology ; Aged ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Adult ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support.

METHODS: We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12.

RESULTS: Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46-1.52; all p ≤ 0.05), those without a bachelor's degree (RR = 1.33; 95% CI = 1.03-1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11-1.90; p < 0.01).

CONCLUSIONS: Long COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.}, } @article {pmid39497009, year = {2024}, author = {Gaetano, C and Atlante, S and Gottardi Zamperla, M and Barbi, V and Gentilini, D and Illi, B and Malavolta, M and Martelli, F and Farsetti, A}, title = {The COVID-19 legacy: consequences for the human DNA methylome and therapeutic perspectives.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39497009}, issn = {2509-2723}, support = {SAC.002.173//IMMUNAGE/ ; RF-2019-12368521//Ministero della Salute Ricerca Corrente 2024 1.07.128/ ; POS-T4 CAL.HUB.RIA T4-AN-09//Ministero della Salute/ ; EU-NRRP M6C2 Inv. 2.1 PNRRMAD-2022-12375790//European Commission/ ; EU PNRR/2022/C9/MCID/I8//European Commission/ ; }, abstract = {The COVID-19 pandemic has left a lasting legacy on human health, extending beyond the acute phase of infection. This article explores the evidence suggesting that SARS-CoV-2 infection can induce persistent epigenetic modifications, particularly in DNA methylation patterns, with potential long-term consequences for individuals' health and aging trajectories. The review discusses the potential of DNA methylation-based biomarkers, such as epigenetic clocks, to identify individuals at risk for accelerated aging and tailor personalized interventions. Integrating epigenetic clock analysis into clinical management could mark a new era of personalized treatment for COVID-19, possibly helping clinicians to understand patient susceptibility to severe outcomes and establish preventive strategies. Several valuable reviews address the role of epigenetics in infectious diseases, including the Sars-CoV-2 infection. However, this article provides an original overview of the current understanding of the epigenetic dimensions of COVID-19, offering insights into the long-term health implications of the pandemic. While acknowledging the limitations of current data, we emphasize the need for future research to unravel the precise mechanisms underlying COVID-19-induced epigenetic changes and to explore potential approaches to target these modifications.}, } @article {pmid39496842, year = {2024}, author = {Pérez Catalán, I and Roig Martí, C and Folgado Escudero, S and Segura Fábrega, A and Varea Villanueva, M and Fabra Juana, S and Domínguez Bajo, E and Herrero Rodríguez, G and Esteve Gimeno, MJ and Palomo de la Sota, D and Cardenal Álvarez, A and Mateu Campos, ML and Usó Blasco, J and Ramos Rincón, JM}, title = {Presence of COVID-19 self-reported symptoms at 12 months in patients discharged from hospital in 2020-2021: a Spanish cross-sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26575}, pmid = {39496842}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Spain/epidemiology ; *Patient Discharge ; Aged ; *Self Report ; Adult ; *SARS-CoV-2/isolation & purification ; Retrospective Studies ; Anxiety/epidemiology ; }, abstract = {The long-term effects of SARS-CoV-2 infection, and their determinants, are still unknown. This study aimed to assess symptoms one year after admission for COVID-19, according to the organ/system involved, and to identify factors. Cross-sectional study with retrospective data collection from March 2020 to February 2021. Inclusion criteria: aged ≥ 18 years and admitted for COVID-19. Exclusion criteria: death, not localized, refusal to participate, cognitive impairment or language barrier. A telephone survey was conducted on long COVID-related symptoms one year after hospital discharge. n = 486. The most frequent symptom groups were neurological (n = 225; 46.3%) and respiratory (n = 201; 41.4%). Multivariable analysis showed that a history of anxiety was significantly associated with psychiatric symptoms (ORa = 2.04, 95%CI = 1.02-4.06), fibromyalgia/chronic fatigue with general symptoms (ORa = 11.59, 95%CI = 1.47-9.34) and obesity with respiratory (ORa 1.90, 95%CI = 1.27-2.83) and musculoskeletal symptoms (ORa 1.96, 95%CI = 1.30-2.96). Male sex was associated with a significantly lower risk of neurological (ORa 0.64, 95%CI = 0.44-0.93), respiratory (ORa 0.45, 95%CI = 0.31-0.67), general (ORa 0.43, 95%CI = 0.29-0.63), psychiatric (ORa 0.34, 95%CI = 0.22-0.51), musculoskeletal (ORa 0.47, 95%CI = 0.32-0.70), dermatological (ORa 0.24, 95%CI = 0.14-0.42) and digestive (ORa 0.38, 95%CI = 0.20-0.73) symptoms. Advanced age (≥ 71 years) also had a protective effect against general (ORa 0.60, 95%CI = 0.39-0.95), psychiatric (ORa 0.39, 95%CI = 0.23-0.64), and dermatological (ORa 0.47, 95%CI = 0.24-0.92) symptoms. Patients admitted for SARS-CoV-2 infection frequently experience symptoms at one year, especially neurological and respiratory symptoms. Female sex, obesity, a history of anxiety and fibromyalgia/chronic fatigue were independent risk factors for presenting symptoms. Advanced age acted as a protective factor.}, } @article {pmid39496183, year = {2024}, author = {Selinger, S}, title = {Patients surviving COVID-19 had lower risk for long COVID in the Omicron vs. earlier eras.}, journal = {Annals of internal medicine}, volume = {177}, number = {11}, pages = {JC131}, doi = {10.7326/ANNALS-24-02441-JC}, pmid = {39496183}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/epidemiology/mortality/prevention & control ; *SARS-CoV-2 ; Male ; Middle Aged ; Female ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Aged ; Pandemics ; Survivors ; }, abstract = {Xie Y, Choi T, Al-Aly Z. Postacute sequelae of SARS-CoV-2 infection in the pre-Delta, Delta, and Omicron eras. N Engl J Med. 2024;391:515-525. 39018527.}, } @article {pmid39495479, year = {2024}, author = {Szögi, T and Borsos, BN and Masic, D and Radics, B and Bella, Z and Bánfi, A and Ördög, N and Zsiros, C and Kiricsi, Á and Pankotai-Bodó, G and Kovács, Á and Paróczai, D and Botkáné, AL and Kajtár, B and Sükösd, F and Lehoczki, A and Polgár, T and Letoha, A and Pankotai, T and Tiszlavicz, L}, title = {Novel biomarkers of mitochondrial dysfunction in Long COVID patients.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39495479}, issn = {2509-2723}, support = {NKFI-FK 132080//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; RRF-2.3.1-21-2022-00003//Nemzeti Kutatási Fejlesztési és Innovációs Hivatal/ ; 739593//Horizon 2020 Framework Programme/ ; TKP-2021-EGA-05//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; 2022-2.1.1-NL-2022-00005//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; TKP2021-NKTA-47//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; POST-COVID2021-36//Magyar Tudományos Akadémia/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30-40% experience persistent symptoms collectively known as Long COVID, post-COVID-19 syndrome, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). These enduring symptoms, including fatigue, respiratory difficulties, body pain, short-term memory loss, concentration issues, and sleep disturbances, can persist for months. According to recent studies, SARS-CoV-2 infection causes prolonged disruptions in mitochondrial function, significantly altering cellular energy metabolism. Our research employed transmission electron microscopy to reveal distinct mitochondrial structural abnormalities in Long COVID patients, notably including significant swelling, disrupted cristae, and an overall irregular morphology, which collectively indicates severe mitochondrial distress. We noted increased levels of superoxide dismutase 1 which signals oxidative stress and elevated autophagy-related 4B cysteine peptidase levels, indicating disruptions in mitophagy. Importantly, our analysis also identified reduced levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in these patients, serving as a novel biomarker for the condition. These findings underscore the crucial role of persistent mitochondrial dysfunction in the pathogenesis of Long COVID. Further exploration of the cellular and molecular mechanisms underlying post-viral mitochondrial dysfunction is critical, particularly to understand the roles of autoimmune reactions and the reactivation of latent viruses in perpetuating these conditions. This comprehensive understanding could pave the way for targeted therapeutic interventions designed to alleviate the chronic impacts of Long COVID. By utilizing circulating ccf-mtDNA and other novel mitochondrial biomarkers, we can enhance our diagnostic capabilities and improve the management of this complex syndrome.}, } @article {pmid39493634, year = {2024}, author = {Salvador-Ruiz, AJ and Moral-Munoz, JA and Salazar, A and Lucena-Anton, D and De Sola, H and Failde, I and Dueñas, M}, title = {Enhancing exercise intervention for patients with post-acute COVID-19 syndrome using mobile health technology: The COVIDReApp randomised controlled trial protocol.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241247936}, pmid = {39493634}, issn = {2055-2076}, abstract = {OBJECTIVES: To analyse the effectiveness of a physical exercise programme guided by a mobile health technology system (COVIDReApp) for patients with post-acute COVID-19 syndrome. This syndrome is a multisystem disease that occurs in people with a history of COVID-19 between 1 and 3 months after the onset of the disease. This study will assess the impact of the intervention on fatigue, post-exertional dyspnoea, quality of life, pain severity, physical fitness, anxiety, depression and cognitive function. We also aim to analyse whether there are associations between the variables studied and the evolution of these associations during follow-up.

DESIGN: A single-blind randomised controlled trial.

METHODS: One hundred patients diagnosed with post-acute COVID-19 will be enrolled and randomly assigned to two groups. The experimental group will perform the intervention through a physical exercise programme guided by the COVIDReApp system, whereas the control group will perform the programme in paper format. Study outcomes will be collected at baseline and at 4, 12 and 24 weeks. Student's t-tests or Mann-Whitney U-tests will be used to analyse differences between groups, mixed ANOVA for differences over time and longitudinal structural equations for associations between variables at follow-up.

DISCUSSION: This study is based on current evidence regarding exercise prescription recommendations for patients with post-acute COVID-19 syndrome. Our intervention is supported by a solid theoretical framework; however, challenges include tailoring the physical exercise programme to everyone's predominant symptoms and ensuring adherence to the programme.

TRIAL REGISTRATION NUMBER: NCT05725538.}, } @article {pmid39493249, year = {2024}, author = {Buonsenso, D and Yonker, LM}, title = {Physical and cognitive stressors exacerbate symptoms in long COVID: more evidence triggering new research and therapeutic needs.}, journal = {The Lancet regional health. Europe}, volume = {46}, number = {}, pages = {101109}, pmid = {39493249}, issn = {2666-7762}, } @article {pmid39493003, year = {2024}, author = {Tabacof, L and Chiplunkar, M and Canori, A and Howard, R and Wood, J and Proal, A and Putrino, D}, title = {Distinguishing pain profiles among individuals with long COVID.}, journal = {Frontiers in rehabilitation sciences}, volume = {5}, number = {}, pages = {1448816}, pmid = {39493003}, issn = {2673-6861}, abstract = {BACKGROUND: For many people with long COVID (LC), new-onset pain is a debilitating consequence. This study examined the nature of new-onset pain and concomitant symptoms in patients with LC to infer mechanisms of pain from the relationships between pain and health-related factors.

METHODS: Pain and other symptoms were evaluated in 153 individuals with LC using the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs, EuroQoL Visual Analog Scale, and Quality of Life in Neurological Disorders. The relationships between pain and patient factors were analyzed using Chi Square and independent t-tests.

RESULTS: 20.3% of individuals who reported new-onset pain had neuropathic pain, which was associated with lower quality of life and higher rates of cognitive dysfunction compared to those with non-neuropathic pain. Other symptoms were similar between groups, however heart-related symptoms were more prevalent in individuals with neuropathic pain and mood swings were more prevalent for individuals with non-neuropathic pain.

CONCLUSIONS: Characterizing the relationships between NP and quality of life in individuals with LC can aid in developing better clinical management strategies. Understanding the associations between NP and cognitive dysfunction provides the imperative foundation for future studies further examining the pathophysiological mechanisms underlying pain development in LC.}, } @article {pmid39491570, year = {2025}, author = {Bensamoun, SF and McGee, KP and Chakouch, M and Pouletaut, P and Charleux, F}, title = {Monitoring of lung stiffness for long-COVID patients using magnetic resonance elastography (MRE).}, journal = {Magnetic resonance imaging}, volume = {115}, number = {}, pages = {110269}, doi = {10.1016/j.mri.2024.110269}, pmid = {39491570}, issn = {1873-5894}, mesh = {Humans ; *Elasticity Imaging Techniques/methods ; *COVID-19/diagnostic imaging ; Male ; *Lung/diagnostic imaging ; Female ; Middle Aged ; Adult ; *Magnetic Resonance Imaging/methods ; SARS-CoV-2 ; Tomography, X-Ray Computed/methods ; Phantoms, Imaging ; Aged ; }, abstract = {PURPOSE: Transaxial CT imaging is the main clinical imaging modality for the assessment of COVID-induced lung damage. However, this type of data does not quantify the functional properties of the lung. The objective is to provide non-invasive personalized cartographies of lung stiffness for long-COVID patients using MR elastography (MRE) and follow-up the evolution of this quantitative mapping over time.

METHODS: Seven healthy and seven long-COVID participants underwent CT and MRE imaging at total lung capacity. After CT test, a senior radiologist visually analyzed the lung structure. Less than one month later, a first MRI (1.5 T, GRE sequence) lung density test followed by a first MRE (SE-EPI sequence) test were performed. Gadolinium-doped water phantom and a pneumatic driver (vibration frequency: 50 Hz), placed on the sternum, were used for MRI and MRE tests, respectively. Personalized cartographies of the stiffness were obtained, by two medical imaging engineers, using a specific post processing (MMDI algorithm). The monitoring (lung density, stiffness) was carried out no later than 11 months for each COVID patient. Wilcoxon's tests and an intra-class correlation coefficient (ICC) were used for statistical analysis.

RESULTS: The density for long-COVID patients was significantly (P = 0.047) greater (170 kg.m[-3]) compared to healthy (125 kg.m[-3]) subjects. After the first MRE test, the stiffness measured for the healthy subjects was in the same range (median value (interquartile range, IQR): 0.93 (0.09) kPa), while the long-COVID patients showed a larger stiffness range (from 1.39 kPa to 2.05 kPa). After a minimum delay of 5 months, the second MRE test showed a decrease of stiffness (from 22 % to 40 %) for every long-COVID patient. The inter-operator agreement was excellent (intra-class correlation coefficient: 0.93 [0.78-0.97]).

CONCLUSION: The MRE test is sensitive enough to monitor disease-induced change in lung stiffness (increase with COVID symptoms and decrease with recovery). This non-invasive modality could yield complementary information as a new imaging biomarker to follow up long-COVID patients.}, } @article {pmid39490617, year = {2025}, author = {Gattoni, C and Abbasi, A and Ferguson, C and Lanks, CW and Decato, TW and Rossiter, HB and Casaburi, R and Stringer, WW}, title = {Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.}, journal = {Respiratory physiology & neurobiology}, volume = {331}, number = {}, pages = {104362}, doi = {10.1016/j.resp.2024.104362}, pmid = {39490617}, issn = {1878-1519}, mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/physiopathology/diagnosis/complications ; *Exercise Test/methods ; Adult ; Oxygen Consumption/physiology ; Post-Acute COVID-19 Syndrome ; Aged ; Respiratory Function Tests ; Exercise Tolerance/physiology ; }, abstract = {BACKGROUND: Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.

METHODS: 15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m[2]] performed a pulmonary function test and two ramp-incremental CPETs separated by 24 hr. CPET variables included gas exchange threshold (GET), peak oxygen uptake (V̇O2peak) and peak work rate (WRpeak). Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0-10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).

RESULTS: mDSQ revealed PEM in 80 % of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40 % of patients (V̇O2peak <80 % predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).

CONCLUSION: PEM symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24 hours, suggests that PEM is not due to impaired recovery of exercise capacity between days.}, } @article {pmid39490027, year = {2024}, author = {An, Y and Guo, Z and Fan, J and Luo, T and Xu, H and Li, H and Wu, X}, title = {Prevalence and measurement of post-exertional malaise in post-acute COVID-19 syndrome: A systematic review and meta-analysis.}, journal = {General hospital psychiatry}, volume = {91}, number = {}, pages = {130-142}, doi = {10.1016/j.genhosppsych.2024.10.011}, pmid = {39490027}, issn = {1873-7714}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology/diagnosis ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVE: Post-exertional malaise (PEM) is a common and debilitating symptom of post-acute COVID-19 syndrome (PACS), and it is also included in the core outcome set for PACS. Our aims are to determine the prevalence of PEM in patients with PACS, and to review the measurement tools utilized in studies assessing PEM among these patients.

METHODS: A systematic literature search was conducted up to 29 February 2024 across four databases: PubMed, EMBASE, Web of Science, and Cochrane Library. Studies were included if they evaluated PACS individuals who had at least one persistent symptom, with the mean or median follow-up duration of at least 3 months after COVID-19 diagnosis or hospital discharge, and specially reported on PEM or any measurement tools utilized to assess PEM. Data extraction and quality assessment were performed independently by two authors.

RESULTS: After screening 953 articles, 12 studies comprising 2665 patients were included in the meta-analysis, and 16 studies were included in the narrative review. The pooled prevalence of PEM among PACS patients at 3 months or more after COVID-19 diagnosis was 0.55 (95 % CI, 0.38, 0.71). Moreover, narrative review identified seven questionnaires used to assess PEM in PACS individuals, with the DePaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) being the most frequently utilized instrument.

CONCLUSION: Our findings indicate that over half of the PACS individuals experience PEM, and seven questionnaires have been identified for researchers to assess PEM. It is imperative to develop effective intervention strategies to treat and alleviate the burden of PEM.}, } @article {pmid39489523, year = {2024}, author = {Holmes, A and Emerson, L and Irving, LB and Tippett, E and Pullin, JM and Young, J and Watters, DA and Hamilton, A}, title = {Persistent symptoms after COVID-19: an Australian stratified random health survey on long COVID.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S12-S17}, doi = {10.5694/mja2.52473}, pmid = {39489523}, issn = {1326-5377}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Female ; Male ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; *Health Surveys ; *SARS-CoV-2 ; Aged ; Quality of Life ; Australia/epidemiology ; Victoria/epidemiology ; Young Adult ; Depression/epidemiology ; Adolescent ; Anxiety/epidemiology ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVE: To determine the impact of persistent symptoms after coronavirus disease 2019 (COVID-19) in an Australian population.

DESIGN, SETTING, PARTICIPANTS: We conducted a statewide health survey of a stratified random sample of adults who had had a confirmed acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19-positive group) and their close contacts (control group). The sample was drawn from Victoria's COVID-19 database between January 2020 and October 2022. Data were collected from 12 688 survey respondents between September 2022 and April 2023 (11 174 in the COVID-19-positive group and 1514 in the control group).

MAIN OUTCOME MEASURES: Persistent new symptoms, recovery, and daily function using validated questionnaires for fatigue, neurocognitive symptoms, anxiety, depression and quality of life.

RESULTS: At a mean of 12.6 months after infection, 4560 respondents in the COVID-19-positive group (39.1%; 95% CI, 37.9-40.3%) reported at least one persistent new symptom, compared with 216 respondents in the control group (20.8%; 95% CI, 18.5-23.1%). A total of 1656 respondents (14.2%; 95% CI, 13.4-15.0%) were classified as having clinical long COVID using the criteria of at least one persistent new symptom and less than 80% recovery three months after the infection. Of the respondents with clinical long COVID, 535 (3.2%; 95% CI, 2.6-3.8%) reported at least moderate problems with usual activities at 12 months after their infection. The proportion of respondents with clinical long COVID was lower for those with more recent infections. The risk factors for clinical long COVID were female sex, age 40-49 years, infection severity, chronic illness, and past anxiety or depression. Factors associated with a decreased risk of having clinical long COVID included infection when the Omicron strain was dominant and infection when the Delta strain was dominant, as compared with when the ancestral strain of the virus was dominant.

CONCLUSION: Persistent symptoms after COVID-19 are common, though with a lower incidence following infection from less virulent strains. Although long COVID can be largely managed in primary care, a minority of people who have persistent symptoms and impaired function may require specialist care pathways, the effectiveness of which should be a focus of future research.}, } @article {pmid39489522, year = {2024}, author = {Watters, DA and Emerson, L}, title = {Long COVID in Victoria.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S3-S4}, doi = {10.5694/mja2.52467}, pmid = {39489522}, issn = {1326-5377}, } @article {pmid39489520, year = {2024}, author = {Kamalakkannan, A and Prgomet, M and Thomas, J and Pearce, C and McGuire, P and Mackintosh, F and Georgiou, A}, title = {Factors associated with general practitioner-led diagnosis of long COVID: an observational study using electronic general practice data from Victoria and New South Wales, Australia.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S18-S22}, doi = {10.5694/mja2.52458}, pmid = {39489520}, issn = {1326-5377}, mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; *COVID-19/epidemiology/diagnosis ; Retrospective Studies ; Victoria/epidemiology ; New South Wales/epidemiology ; Case-Control Studies ; Aged ; Young Adult ; General Practice/statistics & numerical data ; Comorbidity ; General Practitioners/statistics & numerical data ; Practice Patterns, Physicians'/statistics & numerical data ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: To investigate associations between sociodemographic factors, pre-existing chronic comorbidities, and general practitioner-led diagnosis of long COVID.

DESIGN, SETTING, PATIENTS: We conducted a retrospective observational case-control study using de-identified electronic general practice data, recorded between January 2020 and March 2023, from 869 general practice clinics across four primary health networks in Victoria and New South Wales.

MAIN OUTCOME MEASURES: Sociodemographic factors and pre-existing chronic comorbidities associated with general practitioner-led diagnosis of long COVID.

RESULTS: A total of 1588 patients had a recorded general practitioner-led long COVID diagnosis. Females exhibited a higher likelihood of general practitioner-led long COVID diagnosis (adjusted odds ratio [aOR], 1.58; adjusted confidence interval [aCI], 1.35-1.85) compared with males. Patients aged 40-59 years had a higher likelihood of general practitioner-led long COVID diagnosis (aOR, 1.68; aCI, 1.40-2.03) compared with patients aged 20-39 years. The diagnosis was more likely in patients of high socio-economic status (aOR, 1.37; aCI, 1.05-1.79) compared with those of mid socio-economic status. Mental health conditions (aOR, 2.69; aCI, 2.25-3.21), respiratory conditions (aOR, 2.25; aCI, 1.85-2.75), cancer (aOR, 1.64; aCI, 1.15-2.33) and musculoskeletal conditions (aOR, 1.50; aCI, 1.20-1.88) were all significantly associated with general practitioner-led long COVID diagnosis.

CONCLUSIONS: Female sex, middle age, high socio-economic status and pre-existing comorbidities, including mental health conditions, respiratory conditions, cancer and musculoskeletal conditions, were associated with general practitioner-led long COVID diagnosis among general practice patients. These factors largely parallel the emerging international evidence on long COVID and highlight the patient characteristics that practitioners should be cognisant of when patients present with symptoms of long COVID.}, } @article {pmid39489519, year = {2024}, author = {Angeles, MR and Dinh, TTN and Zhao, T and de Graaff, B and Hensher, M}, title = {The economic burden of long COVID in Australia: more noise than signal?.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S31-S39}, doi = {10.5694/mja2.52468}, pmid = {39489519}, issn = {1326-5377}, mesh = {Humans ; Australia/epidemiology ; *Cost of Illness ; *COVID-19/economics/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; Middle Aged ; Fatigue Syndrome, Chronic/economics/epidemiology ; Employment/economics/statistics & numerical data ; Female ; Male ; }, abstract = {OBJECTIVE: To estimate the potential economic burden of long COVID in Australia.

DESIGN: A stock-and-flow model of weekly estimated numbers of people with long COVID (January 2021 to June 2023); application of proxy cost estimates from people living with myalgic encephalomyelitis/chronic fatigue syndrome; time series analysis of labour market and social security datasets.

SETTING: The working age Australian population.

MAIN OUTCOME MEASURES: The likely number of Australians severely impacted by long COVID; the economic cost of long COVID; and the impacts of long COVID, determined by analysis of labour market data.

RESULTS: At its peak in late 2022, between 181 000 and 682 000 Australians may have experienced some long COVID symptoms, of whom 40 000-145 000 may have been severely affected. Severe cases potentially decreased to affecting 10 000-38 000 people by June 2023. The likely economic burden of long COVID in Australia during 2022 was between $1.7 billion and $6.3 billion (some 0.07% to 0.26% of gross domestic product). Labour market data suggest that between 25 000 (February 2023) and 103 000 (June 2023) more working age Australians reported being unable to work due to long term sickness than would have been predicted based on pre-COVID-19 trends. This does not appear to have translated into increased claims for Disability Support Pensions, but numbers of working age Carer Allowance recipients have grown markedly since 2022.

CONCLUSIONS: Long COVID likely imposed a small but significant aggregate toll on the Australian economy, while exposing tens of thousands of Australians to substantial personal economic hardship and contributing to labour market supply constraints. Yet while some signal from long COVID is discernible in the labour force data, Australia lacks adequate direct surveillance data to securely guide policy making.}, } @article {pmid39489518, year = {2024}, author = {Adhikari, A and Maddumage, J and Eriksson, EM and Annesley, SJ and Lawson, VA and Bryant, VL and Gras, S}, title = {Beyond acute infection: mechanisms underlying post-acute sequelae of COVID-19 (PASC).}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S40-S48}, doi = {10.5694/mja2.52456}, pmid = {39489518}, issn = {1326-5377}, support = {1159272//National Health and Medical Research Council/ ; }, mesh = {Humans ; *COVID-19/complications/immunology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Gastrointestinal Microbiome ; }, abstract = {Immune dysregulation is a key aspect of post-acute sequelae of coronavirus disease 2019 (PASC), also known as long COVID, with sustained activation of immune cells, T cell exhaustion, skewed B cell profiles, and disrupted immune communication thereby resulting in autoimmune-related complications. The gut is emerging as a critical link between microbiota, metabolism and overall dysfunction, potentially sharing similarities with other chronic fatigue conditions and PASC. Immunothrombosis and neurological signalling dysfunction emphasise the complex interplay between the immune system, blood clotting, and the central nervous system in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clear research gaps in the design of PASC studies, especially in the context of longitudinal research, stand out as significant areas of concern.}, } @article {pmid39489515, year = {2024}, author = {Flannigan, KM and Flannigan, GM}, title = {Living with long COVID and its impact on family and society: a couple's view.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S10-S11}, doi = {10.5694/mja2.52466}, pmid = {39489515}, issn = {1326-5377}, } @article {pmid39489514, year = {2024}, author = {Wrench, JM and Seidel Marks, LR}, title = {An allied health model of care for long COVID rehabilitation.}, journal = {The Medical journal of Australia}, volume = {221 Suppl 9}, number = {}, pages = {S5-S9}, doi = {10.5694/mja2.52457}, pmid = {39489514}, issn = {1326-5377}, } @article {pmid39489282, year = {2025}, author = {Epstein-Shuman, A and Hunt, JH and Caturegli, P and Winguth, P and Fernandez, RE and Rozek, GM and Zhu, X and DiRico, NA and Jamal, A and Hsieh, YH and Manabe, YC and Redd, AD and Reynolds, SJ and Antar, AAR and Laeyendecker, O}, title = {Autoantibodies directed against interferon alpha, nuclear antigens, cardiolipin, and beta 2 glycoprotein 1 are not induced by SARS-CoV-2 or associated with long COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {150}, number = {}, pages = {107289}, doi = {10.1016/j.ijid.2024.107289}, pmid = {39489282}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/immunology ; Male ; *SARS-CoV-2/immunology ; *Autoantibodies/blood/immunology ; Female ; Middle Aged ; Adult ; *beta 2-Glycoprotein I/immunology ; Aged ; *Interferon-alpha/immunology/blood ; Cardiolipins/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Autoantibodies (AAbs) directed against interferon alpha (aIFNα), nuclear antigens (ANAs), anti-cardiolipin (aCL), and anti-beta 2 glycoprotein 1 (aβ2GP1), have been demonstrated to significantly correlate with the severity of acute Coronavirus Disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces these AAbs and whether they are associated with long COVID remains unclear.

METHODS: The potential induction of aIFNα, ANAs, aCL, and aβ2GP1 by SARS-CoV-2 was assessed by measuring these AAbs in 224 pre- and post-infection paired serum samples from the Johns Hopkins Hospital Emergency Department (JHHED). The relationship between these AAbs and long COVID was assessed using 60 serum samples from participants in the Outpatient SARS-CoV-2 Mild and Asymptomatic Infection Response and Transmission study.

RESULTS: We found no evidence that these AAbs were induced in the JHHED cohort and no significant difference in their prevalence between patients with (n = 30) and without (n = 30) long COVID in the OutSMART cohort.

CONCLUSION: These findings do not support the hypotheses that SARS-CoV-2 induces these AAbs or that they are related to long COVID.}, } @article {pmid39483438, year = {2024}, author = {Brightman, L and Huang, HC and Georgousopoulou, E}, title = {Predictors of ongoing attendance at an Australian publicly funded specialist obesity service.}, journal = {Obesity science & practice}, volume = {10}, number = {6}, pages = {e70010}, pmid = {39483438}, issn = {2055-2238}, abstract = {INTRODUCTION: There is a demand for publicly funded specialist obesity services in Australia. A range of factors can impact on patient attendance which can result in poorer health outcomes.

OBJECTIVE: To identify patient factors that predict ongoing in-person attendance following initial medical assessment at the Canberra Obesity Management Service.

METHODS: Data were collated from two retrospective reviews (July 2016-June 2017 and July 2018-June 2019). Predictive modeling was used to determine the likelihood of ongoing attendance.

RESULTS: A total of 396 patients were identified. Mean age was 45.4 years (SD 13.1), mean weight was 139.5 kg (SD 27.8) and mean Body Mass Index was 49.87 kg/m[2] (SD 8.7). Demographics and anthropometrics were not predictive of ongoing attendance. Patients with a higher comorbidity burden were more likely to continue attending (p < 0.001). Patients with obstructive sleep apnea (OSA) were 4.9 times more likely to continue attending (p < 0.001). Hypertension was more common among patients who continued attending (p = 0.005); however, this relationship was no longer significant when using a multi-adjusted model. Comorbid depression and/or anxiety diagnoses were not predictive of ongoing attendance although the p-value for anxiety severity classification approached significance.

CONCLUSIONS: Findings are consistent with existing evidence linking OSA and attendance at specialist obesity services. Hypertension was predictive of ongoing attendance and warrants further research. Determining if anxiety is a true barrier to attendance at specialist obesity services may have implications in terms of optimizing diagnosis and treatment prior to referral or in the early stages of obesity management.}, } @article {pmid39482691, year = {2024}, author = {Nwankwo, H and Mason, J and Underwood, M and Bruce, J and Lall, R and Ji, C and Ratna, M and McGregor, G}, title = {Cost-effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-COVID-19 condition after hospitalisation for COVID-19: the REGAIN RCT.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {1326}, pmid = {39482691}, issn = {1472-6963}, support = {NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; NIHR132046//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/rehabilitation/economics/epidemiology ; *Cost-Benefit Analysis ; Male ; United Kingdom ; Female ; Adult ; Hospitalization/economics ; Quality-Adjusted Life Years ; Quality of Life ; Middle Aged ; SARS-CoV-2 ; State Medicine/economics ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Following the COVID-19 pandemic, millions of people continue to experience ongoing physical and mental health sequelae after recovery from acute infection. There is currently no specific treatment for the diverse symptoms associated with post-COVID-19 condition. Physical and mental health rehabilitation may help improve quality of life in such patients. This study reports the cost-effectiveness of a programme of physical and mental health rehabilitation compared to best practice usual care in people with post-COVID-19 condition who were previously hospitalised.

METHODS: We conducted an economic evaluation within a randomised controlled trial from the perspective of the UK national health service (NHS) and personnel social services perspective (PSS). Resource used and health-related quality of life were collected using bespoke questionnaire and the EQ-5D-5 L questionnaire at three, six, and 12 months. Incremental costs and quality adjusted life years accrued over the follow-up period were estimated and reported as the incremental cost-effectiveness ratio. Estimate uncertainty was managed by multiple imputation and bootstrapping cost-effectiveness estimates; and displayed graphically on the cost-effectiveness plane.

RESULTS: Over a 12-month time horizon, incremental costs and QALYs were £305 (95% CI: -123 to 732) and 0.026 (95% CI: -0.005 to 0.052) respectively. The ICER was £11,941 per QALY indicating cost-effective care. Sensitivity analyses supported the base case findings. The probability of the intervention being cost-effective at a £30,000 per QALY willingness-to-pay threshold was 84%.

CONCLUSION: The within-trial economic evaluation suggested that people with post-COVID-19 condition after hospitalisation should be offered a programme of physical and mental health rehabilitation as it likely reflects a cost-effective use of NHS resources. Hospitalisation for COVID-19 has become less commonplace: further evaluation in non-hospitalised patients may be worthwhile.

TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448 23rd November 2020.}, } @article {pmid39488359, year = {2024}, author = {Leung, DYM}, title = {Post-pandemic, long COVID persists.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {133}, number = {5}, pages = {489-490}, doi = {10.1016/j.anai.2024.08.031}, pmid = {39488359}, issn = {1534-4436}, } @article {pmid39488240, year = {2024}, author = {Lukkunaprasit, T and Satapornpong, P and Kulchanawichien, P and Prawang, A and Limprasert, C and Saingam, W and Permsombut, C and Panidthananon, W and Vutthipong, A and Lawanprasert, Y and Pourpongpan, P and Wongwiwatthananukit, S and Songsak, T and Pradubyat, N}, title = {Impact of combined plant extracts on long COVID: An exploratory randomized controlled trial.}, journal = {Complementary therapies in medicine}, volume = {87}, number = {}, pages = {103107}, doi = {10.1016/j.ctim.2024.103107}, pmid = {39488240}, issn = {1873-6963}, mesh = {Humans ; Male ; *Plant Extracts/therapeutic use/pharmacology ; Female ; Middle Aged ; Double-Blind Method ; *Quality of Life ; Adult ; *COVID-19 Drug Treatment ; *C-Reactive Protein/analysis ; Thailand ; COVID-19 ; SARS-CoV-2/drug effects ; Post-Acute COVID-19 Syndrome ; Alpinia/chemistry ; Piper nigrum/chemistry ; Citrus/chemistry ; Aged ; Phytotherapy/methods ; }, abstract = {BACKGROUND: Long COVID have posed a global health burden since the COVID-19 pandemic. This study aimed to evaluate the efficacy and safety of a combined plant extract (CPE) formulation, containing Citrus aurantifolia, Tiliacora triandra, Cannabis sativa, Alpinia galanga, and Piper nigrum, in participants with long COVID. A newly developed long COVID symptom questionnaire was used to evaluate outcomes.

METHODS: This randomized, double-blinded, placebo-controlled trial was conducted at the College of Pharmacy, Rangsit University, Thailand. Participants were randomly assigned to receive either a CPE supplement (4500 mg/day) or a placebo for 7 days. Primary outcomes were changes in C-reactive protein (CRP) levels and the total symptom score (ranging from 0 to 57 points). Secondary outcomes included full recovery/improvement of long COVID symptoms, health-related quality of life (HRQOL), and adverse events.

RESULTS: A total of 66 participants were enrolled, with 33 in each group. The CPE supplement did not significantly reduce CRP levels, with a median difference (MD) (95 % CI) of -0.05 (-0.49, 0.39) mg/L compared to placebo. However, the CPE group showed a reduction in the total symptom score [MD (95 % CI) of -4.00 (-7.58, -0.42)], and a reduction in overall moderate to severe symptoms [RR (95 % CI) of 0.57 (0.35, 0.91)], moderate to severe fatigue [RR (95 % CI) of 0.25 (0.08, 0.81)], and moderate to severe post-exertional malaise (PEM) [RR (95 % CI) of 0.35 (0.16, 0.78)]. Changes in HRQOL scores did not differ significantly between groups. Adverse events were mostly mild and resolved by the end of the follow-up period.

CONCLUSIONS: Our study suggests potential benefits of the CPE in alleviating moderate to severe long COVID symptoms, particularly fatigue and PEM, with an acceptable safety profile. However, larger-scale trials are necessary to validate these findings, and assessing the reliability of the long COVID symptom questionnaire is essential before its application in future studies.

TRIAL REGISTRATION NUMBER: TCTR20230131004 (Registration date: 2023-01-31, Thai Clinical Trials Registry).}, } @article {pmid39485894, year = {2024}, author = {Borghi-Silva, A and Goulart, CDL and Silva, RN and Back, GD and Camargo, PF and Trimer, R and Teles, SN and Sampaio, LMM}, title = {Impact of COVID-19 on Exercise-Based Pulmonary Rehabilitation: What Lessons Have We Learned?.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {44}, number = {6}, pages = {409-416}, pmid = {39485894}, issn = {1932-751X}, mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Exercise Therapy/methods ; SARS-CoV-2 ; Pulmonary Disease, Chronic Obstructive/rehabilitation ; Telerehabilitation ; Pandemics ; }, abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic had a major global impact on health care, including the delivery, modality, and importance of outcomes in pulmonary rehabilitation (PR). This review discusses the impact of the pandemic on PR and the changes that were required to maintain its delivery. This article reviews the current evidence on PR during the COVID-19 pandemic period, focusing on delivery models, modalities, outcomes, perspectives, and barriers. A search of the MEDLINE, Embase, and SciELO databases and the Cochrane Library on this topic was conducted between December 1, 2019 and August 1, 2023. Studies were reviewed and relevant topics were included in this narrative. Rehabilitation of patients with severe acute COVID-19 and symptoms of long COVID has been challenging. The number of rehabilitation programs worldwide is still low, and community-based programs are still rare. Integrated programs with a multidisciplinary approach and exercise therapy with individualized prescription based on symptoms have been an interesting strategy. Telerehabilitation and outpatient rehabilitation are both effective in the treatment of patients with chronic obstructive pulmonary disease. However, the uptake of PR remains considerably low, and technological barriers for patients and lack of technological resources in low-income countries affect the delivery of these services in much of the world.}, } @article {pmid39485635, year = {2024}, author = {Zakaria, D and Demers, A and Cheta, N and Aziz, S and Abdullah, P}, title = {Factors associated with the development, severity, and resolution of post COVID-19 condition in adults living in Canada, January 2020 to August 2022.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {}, number = {}, pages = {}, pmid = {39485635}, issn = {1920-7476}, abstract = {OBJECTIVES: We aimed to characterize the burden of post COVID-19 condition (PCC) among adults in Canada and identify factors associated with its occurrence, severity, and resolution.

METHODS: We used self-report data from a population-based cross-sectional probability survey of adults in Canada conducted between April and August 2022. Incidence and prevalence of PCC were estimated using confirmed infections, as well as confirmed and suspected combined. Multivariable modeling using confirmed cases identified associated factors.

RESULTS: As of August 2022, 17.2% (95% CI 15.7, 18.8) of adults with confirmed infections and 16.7% (95% CI 15.5, 18.0) of adults with confirmed or suspected infections experienced PCC, translating to 3.3% (95% CI 3.0, 3.6) and 4.4% (95% CI 4.1, 4.8) of all adults, respectively. Age less than 65 years (aORs of 1.75 to 2.14), more pre-existing comorbidities (aORs of 1.75 to 3.57), and a more severe initial infection (aORs of 3.52 to 9.69) were all associated with higher odds of PCC, while male sex at birth (aOR = 0.54, 95% CI 0.41, 0.70), identifying as Black (aOR = 0.23, 95% CI 0.11, 0.51), and being infected after 2020 (aORs of 0.24 to 0.55) were associated with lower odds. Those residing in a rural area (aOR = 2.31, 95% CI 1.35, 3.93), or reporting a disability (aOR = 2.87, 95% CI 1.14, 7.25), pre-existing chronic lung condition (aOR = 5.47, 95% CI 1.85, 16.12) or back problem (aOR = 2.34, 95% CI 1.26, 4.36), or PCC headache (aOR = 2.47, 95% CI 1.60, 3.83) or weakness (aOR = 2.27, 95% CI 1.41, 3.68) had higher odds of greater limitations in daily activities, while males had lower odds (aOR = 0.54, 95% CI 0.34, 0.85). Two or more pre-existing chronic conditions (aHRs from 0.33 to 0.38), or PCC symptoms relating to the heart (aHR = 0.25, 95% CI 0.07, 0.90), brain fog (aHR = 0.44, 95% CI 0.23, 0.86), or stress/anxiety (aHR = 0.48, 95% CI 0.24, 0.96) were associated with a decreased rate of symptom resolution.

CONCLUSION: Over the first two and a half years of the pandemic, a substantial proportion of infected adults in Canada reported PCC. Females and people with comorbidities were disproportionately impacted.}, } @article {pmid39482903, year = {2024}, author = {Pagliuca, A and Kaul, S and Goodyear, CS and Lee, L}, title = {Prevention is better than cure: immunocompromised people need COVID-19 prevention therapies now.}, journal = {Infectious diseases (London, England)}, volume = {56}, number = {12}, pages = {1107-1110}, doi = {10.1080/23744235.2024.2405210}, pmid = {39482903}, issn = {2374-4243}, mesh = {Humans ; *COVID-19/prevention & control/immunology ; *Immunocompromised Host ; United Kingdom ; *SARS-CoV-2/immunology ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; }, abstract = {Immunocompromised people are facing ongoing inequality in health outcomes because of COVID-19. Let's remain ambitious and improve availability and access to COVID-19 prevention therapies that protect patients and aid management. This article brings together opinions from four experts based in the United Kingdom who specialise in immunology, solid organ transplantation, respiratory medicine and critical care, oncology and haematology. In this article, they communicate the impact of SARS-CoV-2 infection on vulnerable patients with underlying conditions and the need for immediate policies to protect vulnerable people from COVID-19.}, } @article {pmid39482218, year = {2025}, author = {Guedj, E and Cionca, A and Péron, JA and Ayubcha, C and Assal, F and Horowitz, T and Alavi, A}, title = {Long Coronavirus Disease and the Brain: Molecular Neuroimaging Insights into Neurologic and Psychiatric Sequelae.}, journal = {PET clinics}, volume = {20}, number = {1}, pages = {39-55}, doi = {10.1016/j.cpet.2024.09.013}, pmid = {39482218}, issn = {1879-9809}, mesh = {Humans ; *Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Mental Disorders/diagnostic imaging/etiology ; *Neuroimaging/methods ; Positron-Emission Tomography/methods ; *Post-Acute COVID-19 Syndrome/complications/diagnostic imaging ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has led to a variety of health challenges, with "long COVID" emerging as a widespread and debilitating post-acute syndrome among a considerable number of infected patients. This PET review synthesizes current evidence of the neurologic and psychiatric sequelae of COVID. This review also explores the pathophysiological mechanisms of these results, including astrocyte dysfunction and glutamate dysregulation, as well as the multimodal comparison to MR imaging findings. The findings underscore the potential for long-term brain injury. Additionally, the authors discuss the role of advanced imaging multimodal techniques in diagnosing, monitoring, and guiding treatment strategies for long COVID.}, } @article {pmid39479770, year = {2024}, author = {Kohli, M and Maschio, M and Lee, A and Joshi, K and Carroll, S and Balogh, O and Van de Velde, N and Beck, E}, title = {The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2024 vaccines in the United Kingdom.}, journal = {Journal of medical economics}, volume = {27}, number = {1}, pages = {1359-1372}, doi = {10.1080/13696998.2024.2413288}, pmid = {39479770}, issn = {1941-837X}, mesh = {Humans ; *Cost-Benefit Analysis ; United Kingdom/epidemiology ; *COVID-19/prevention & control/epidemiology/economics ; *COVID-19 Vaccines/economics ; *Quality-Adjusted Life Years ; Middle Aged ; Adult ; Aged ; *SARS-CoV-2 ; Adolescent ; Young Adult ; Child ; Hospitalization/economics/statistics & numerical data ; Child, Preschool ; Infant ; Male ; Female ; mRNA Vaccines ; }, abstract = {AIMS: To estimate the potential clinical impact and cost-effectiveness of a United Kingdom (UK) Autumn 2024 vaccination campaign with an updated Moderna COVID-19 vaccine in adults ≥65 years and eligible persons 6 months to 64 years of age over a 1-year time horizon (September 2024-August 2025).

MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was adapted to reflect COVID-19 cases in the UK. Numbers of symptomatic infections, COVID-19-related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) were predicted using a decision tree. The incremental cost-effectiveness ratio (ICER) of an updated Moderna mRNA vaccine (Moderna Autumn 2024 Campaign) was compared to No Autumn 2024 vaccine and to an updated Pfizer-BioNTech mRNA Autumn 2024 vaccine, from a healthcare perspective.

RESULTS: The Moderna Autumn 2024 Vaccination Campaign is predicted to decrease the expected 8.3 million symptomatic infections with no vaccination by 19% to 6.7 million. Hospitalizations, long COVID cases, and deaths are expected to decline by 27,000 (-38%), 59,000 (-19%), and 6,000 (-43%), respectively. The Moderna Autumn 2024 Campaign will increase QALYs by 78,000 and costs by £665 million, yielding an ICER of £8,500/QALY gained. Sensitivity analyses suggest that vaccine effectiveness (VE) and waning, symptomatic infection incidence, hospitalization rates, and mortality rates drive cost-effectiveness. Vaccination remains cost-effective when lowering the target population to ≥50 years. Use of the Moderna vaccine is expected to prevent 8,000 more hospitalizations and 1,700 more deaths than the updated Pfizer-BioNTech vaccine.

CONCLUSIONS: Vaccination of the eligible population would contribute to significant reductions in hospitalizations, deaths, and long COVID in the UK in the 2024-2025 season. Expanding the target population continues to be cost-effective. Use of the Moderna Autumn 2024 Campaign is predicted to reduce SARS-CoV-2 infections and associated outcomes in a cost-effective manner and will contribute to a more resilient healthcare system in the UK.}, } @article {pmid39479090, year = {2024}, author = {Feiz, H and Castellano, C and Feiz, L}, title = {Complications of Long COVID: Unraveling a Case of Very-Late-Onset Myasthenia Gravis.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e70552}, pmid = {39479090}, issn = {2168-8184}, abstract = {Myasthenia gravis (MG) is defined as an autoimmune neuromuscular disorder where autoantibodies disrupt synaptic transmission at the neuromuscular junction by targeting the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or other proteins related to the AChR complex. This disruption leads to characteristic muscle weakness and rapid fatigability. Clinically, MG is classified based on the age of onset into three distinct categories: early-onset MG (younger than 50 years), late-onset MG (between 50 and 64 years), and very-late-onset MG (65 years and older). We present a rare case of an 81-year-old man who presented with dysarthria, shortness of breath, diplopia, and oropharyngeal dysphagia to both solids and liquids for approximately seven days and was noted to be more progressive in the last 48 hours prior to his presentation to the emergency room. Upon arrival at the emergency room, he complained of shortness of breath and diplopia. Of note, approximately four months prior to this admission, he was diagnosed with COVID-19 pneumonia and was treated appropriately with remdesivir and corticosteroids. He had an uneventful COVID-19 pneumonia hospitalization and was discharged home. Given the progressive nature of his symptomatology, particularly dyspnea, he was transferred to the ICU for further evaluation and treatment. Laboratory results were positive for AChR binding, blocking, and modulating antibodies, confirming the diagnosis of MG. The patient received treatment consisting of pyridostigmine, a pulse dose of methylprednisolone, and intravenous immunoglobulin (IVIG) therapy. This case is unique and highlights a case of a very late onset of MG and the manifestation of new-onset MG four months following COVID-19. Additionally, this patient had a very delayed onset of MG symptoms, as he presented four months after his infection with COVID-19, compared to the average onset of reported cases of post-COVID MG being four to eight weeks post-infection with COVID-19. This uniquely delayed onset, occurring beyond a three-month window post-COVID-19 infection, aligns with the criteria established by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) for a diagnosis of "Post-COVID Condition," also known as "Long COVID." This case illustrates the intricate link between post-viral states and autoimmune responses, particularly in geriatric patients. The pathophysiology linking COVID-19 to MG primarily involves immune dysregulation triggered by the viral infection, which may disrupt immune tolerance and lead to clinical autoimmunity. This case stresses the need for vigilance in diagnosis and managing neurological complications in the context of viral respiratory illnesses, particularly in vulnerable populations.}, } @article {pmid39478809, year = {2024}, author = {Mfouth Kemajou, P and Besse-Hammer, T and Lebouc, C and Coppieters, Y}, title = {Cluster analysis identifies long COVID subtypes in Belgian patients.}, journal = {Biology methods & protocols}, volume = {9}, number = {1}, pages = {bpae076}, pmid = {39478809}, issn = {2396-8923}, abstract = {Severe acute respiratory syndrome coronavirus infection presents complications known as long COVID, a multisystemic organ disease which allows multidimensional analysis. This study aims to uncover clusters of long COVID cases and establish their correlation with the clinical classification developed at the Clinical Research Unit of Brugmann University Hospital, Brussels. Such an endeavour is instrumental in customizing patient management strategies tailored to the unique needs of each distinct group. A two-stage multidimensional exploratory analysis was performed on a retrospective cohort of 205 long COVID patients, involving a factorial analysis of mixed data, and then hierarchical clustering post component analysis. The study's sample comprised 76% women, with an average age of 44.5 years. Three clinical forms were identified: long, persistent, and post-viral syndrome. Multidimensional analysis using demographic, clinical, and biological variables identified three clusters of patients. Biological data did not provide sufficient differentiation between clusters. This emphasizes the importance of identifying or classifying long COVID patients according to their predominant clinical syndrome. Long COVID phenotypes, as well as clinical forms, appear to be associated with distinct pathophysiological mechanisms or genetic predispositions. This underscores the need for further research.}, } @article {pmid39478711, year = {2024}, author = {Jitpanya, C and Maninet, S and Saengkham, P}, title = {Prevalence and Predictors of Fatigue among Thai Women after COVID-19 Infection.}, journal = {Iranian journal of nursing and midwifery research}, volume = {29}, number = {5}, pages = {563-567}, pmid = {39478711}, issn = {1735-9066}, abstract = {BACKGROUND: Several people suffered from fatigue after recovering from coronavirus disease 2019 (COVID-19). However, limited studies focused on fatigue in women who recovered from COVID-19 infection. This study aimed to investigate the prevalence of fatigue among Thai women after COVID-19 infection and to identify predictive factors, including depression, anxiety, fear, and insomnia.

MATERIALS AND METHODS: A cross-sectional research design using convenience sampling was conducted from October 2022 to January 2023. A total of 142 Thai women after COVID-19 infection were recruited from two urban communities located in the Bangkok Metropolitan area, Thailand. The participants completed self-reported questionnaires, including the demographic and illness-related data questionnaire, the Depress Anxiety Stress Scales, the Insomnia Severity Index, the Fear of Progression Questionnaire, and the Fatigue Severity Scale. Data were analyzed using mean, standard deviation, range, Pearson's product-moment correlations, and stepwise multiple regression.

RESULTS: All (100%) participants returned the questionnaires. After recovering from COVID-19 infection for at least 1 month or longer, 39.40% of the participants reported fatigue. The multiple regression analysis revealed that fear, anxiety, and insomnia collectively contributed to 47% of the variance in the participants' fatigue (R[2] = 0.47; p < 0.001).

CONCLUSIONS: Nearly two-quarters of Thai women after recovering from COVID-19 infection experienced fatigue. To prevent fatigue among Thai women after COVID-19 infection, it is necessary to help them overcome feelings of fear and anxiety. Furthermore, nursing interventions aiming to alleviate insomnia should be implemented.}, } @article {pmid39477428, year = {2024}, author = {Moldovan, AF and Ghitea, TC and Babeș, K and Manole, F}, title = {Long-term Impacts of Long COVID: Increased Incidence of Cardiomyopathies, Joint Diseases, and Psychoanxiety Disorders.}, journal = {In vivo (Athens, Greece)}, volume = {38}, number = {6}, pages = {3022-3032}, pmid = {39477428}, issn = {1791-7549}, mesh = {Humans ; *COVID-19/epidemiology/psychology/complications ; Male ; Female ; Aged ; Middle Aged ; Incidence ; *Anticoagulants/therapeutic use ; *Cardiomyopathies/epidemiology/psychology ; *SARS-CoV-2 ; Thromboembolism/etiology/epidemiology ; Vitamin K/antagonists & inhibitors ; Aged, 80 and over ; Adult ; }, abstract = {BACKGROUND/AIM: The COVID-19 pandemic has intensified inquiries into the interplay between diabetes and disease severity, and the long-term impact of long-COVID. This study specifically explored the implications of different antithrombotic treatments on COVID-19 patients. It aimed to assess the long-term efficacy and safety of Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) in mitigating thromboembolic complications in COVID-19 patients.

PATIENTS AND METHODS: We conducted a study on 157 patients diagnosed with COVID-19 from August 2021 to August 2023. The study evaluated shifts in anticoagulant therapy recommendations, tracking the transition from VKA to DOACs, and analyzed associated health outcomes.

RESULTS: A significant shift from VKA to DOACs prescriptions was observed, especially in high-risk patients. Despite the change in antithrombotic treatments, incidences of varices and varices with hemorrhoids increased by 2.6% and 3.2%, respectively. Long-COVID was also linked to higher occurrences of diabetes and gastrointestinal diseases. Joint diseases rose by 14%, indicating persistent inflammation. Cardiomyopathies increased by 3.9%, predominantly in high-risk groups, and psychoanxiety disorders surged by 39.5%, highlighting the need for further research. DOAC usage was more common in older age groups, with a 10.2% increase in recommendations among high-risk patients (p<0.05).

CONCLUSION: The study underscores the evolving landscape of antithrombotic therapy in managing COVID-19 complications. Despite the increased use of DOACs, the rise in various health conditions suggests the necessity for personalized treatment strategies tailored to patient risk profiles.}, } @article {pmid39475394, year = {2024}, author = {Curvelo, RD and Ribeiro, AC and da Silva André Uehara, SC}, title = {Health care for patients with long COVID: a scoping review.}, journal = {Revista da Escola de Enfermagem da U S P}, volume = {58}, number = {}, pages = {e20240056}, pmid = {39475394}, issn = {1980-220X}, mesh = {Humans ; *COVID-19/therapy ; Delivery of Health Care/organization & administration ; Post-Acute COVID-19 Syndrome ; Physical Therapy Modalities ; Telerehabilitation/organization & administration ; }, abstract = {OBJECTIVE: To map the scientific evidence on the care offered to health service users with Long Covid-19.

METHOD: This is a scoping review based on the methods of the Joanna Briggs Institute. Primary studies were included, in Portuguese, English and Spanish, published between December 2019 and June 2023, in the Virtual Health Library, Web of Science, Scopus, PUBMED, SciELO and LITCovid LongCovid databases.

RESULTS: Of the ١٣ articles analyzed, it stands out that the care provided to patients with Long Covid is associated with drug prescription, indication of physical exercises, telerehabilitation and physiotherapy.

CONCLUSION: A fragmentation was identified in the care provided to users of health services with Long Covid, with care directed only at isolated symptoms, without addressing the biopsychosocial care that people with this condition need.}, } @article {pmid39474404, year = {2024}, author = {Bistagnino, F and Pizzi, D and Mantovani, F and Antonino, JR and Tovani-Palone, MR}, title = {Long COVID and gut candidiasis: What is the existing relationship?.}, journal = {World journal of gastroenterology}, volume = {30}, number = {37}, pages = {4104-4114}, pmid = {39474404}, issn = {2219-2840}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Candidiasis/epidemiology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Diseases/virology/epidemiology/microbiology/physiopathology ; }, abstract = {Since the beginning of the coronavirus disease (COVID) 2019 pandemic, thousands of articles on the topic have been published, and although there is a growing trend of research on another associated condition, long coronavirus disease, important points still remain to be clarified in this respect. Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID. However, one of the existing gaps that requires further investigation concerns a possible relationship between gut candidiasis and long COVID. While recent studies also suggest an interplay between the occurrence of these two conditions, it is not yet fully clear how this may happen, as well as the specifics regarding the possible pathophysiological mechanisms involved. In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID, a better understanding of the clinical presentation, pathophysiology and clinical management of such a relationship should be essential and useful for both, additional advances towards more targeted research and appropriate case management. Knowing more about the signs, symptoms, and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population. In light of this and the need for better outcomes, here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis, as well as suggest propositions for future related research.}, } @article {pmid39474148, year = {2024}, author = {Bergaglio, T and Synhaivska, O and Nirmalraj, PN}, title = {3D Holo-tomographic Mapping of COVID-19 Microclots in Blood to Assess Disease Severity.}, journal = {Chemical & biomedical imaging}, volume = {2}, number = {3}, pages = {194-204}, pmid = {39474148}, issn = {2832-3637}, abstract = {The coronavirus disease 2019 (COVID-19) has impacted health globally. Cumulative evidence points to long-term effects of COVID-19 such as cardiovascular and cognitive disorders, diagnosed in patients even after the recovery period. In particular, micrometer-sized blood clots and hyperactivated platelets have been identified as potential indicators of long COVID. Here, we resolve microclot structures in the plasma of patients with different subphenotypes of COVID-19 in a label-free manner, using 3D digital holo-tomographic microscopy (DHTM). Based on 3D refractive index (RI) tomograms, the size, dry mass, and prevalence of microclot composites were quantified and then parametrically differentiated from fibrin-rich microclots and platelet aggregates in the plasma of COVID-19 patients. Importantly, fewer microclots and platelet aggregates were detected in the plasma of healthy controls compared to COVID-19 patients. Our imaging and analysis workflow is built around a commercially available DHT microscope capable of operation in clinical settings with a 2 h time period from sample preparation and data acquisition to results.}, } @article {pmid39473828, year = {2024}, author = {Dolin, G and Saitwal, H and Bertodatti, K and Mueller, S and Bierman, AS and Suls, J and Brandt, K and Camara, DS and Leppry, S and Jones, E and Gallego, E and Carlson, D and Norton, J}, title = {Establishing data elements and exchange standards to support long COVID healthcare and research.}, journal = {JAMIA open}, volume = {7}, number = {3}, pages = {ooae095}, pmid = {39473828}, issn = {2574-2531}, abstract = {OBJECTIVE: The Multiple Chronic Conditions (MCCs) Electronic Care (e-Care) Plan project aims to establish care planning data standards for individuals living with MCCs. This article reports on the portion of the project focused on long COVID and presents the process of identifying and modeling data elements using the HL7 Fast Healthcare Interoperability Resources (FHIR) standard.

MATERIALS AND METHODS: Critical data elements for managing long COVID were defined through a consensus-driven approach involving a Technical Expert Panel (TEP). This involved 2 stages: identifying data concepts and establishing electronic exchange standards.

RESULTS: The TEP-identified and -approved long COVID data elements were mapped to the HL7 US Core FHIR profiles for syntactic representation, and value sets from standard code systems were developed for semantic representation of the long COVID concepts.

DISCUSSION: Establishing common long COVID data standards through this process, and representing them with the HL7 FHIR standard, facilitates interoperable data collection, benefiting care delivery and patient-centered outcomes research (PCOR) for long COVID. These standards may support initiatives including clinical and pragmatic trials, quality improvement, epidemiologic research, and clinical and social interventions.By building standards-based data collection, this effort accelerates the development of evidence to better understand and deliver effective long COVID interventions and patient and caregiver priorities within the context of MCCs and to advance the delivery of coordinated, person-centered care.

CONCLUSION: The open, collaborative, and consensus-based approach used in this project will enable the sharing of long COVID-related health concerns, interventions, and outcomes for patient-centered care coordination across diverse clinical settings and will facilitate the use of real-world data for long COVID research.}, } @article {pmid39472619, year = {2024}, author = {Saheb Sharif-Askari, F and Ali Hussain Alsayed, H and Saheb Sharif-Askari, N and Al Sayed Hussain, A and Al-Muhsen, S and Halwani, R}, title = {Nirmatrelvir plus ritonavir reduces COVID-19 hospitalization and prevents long COVID in adult outpatients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25901}, pmid = {39472619}, issn = {2045-2322}, mesh = {*Ritonavir/therapeutic use ; Humans ; Female ; Male ; Middle Aged ; *COVID-19 Drug Treatment ; *Hospitalization/statistics & numerical data ; Retrospective Studies ; Adult ; *SARS-CoV-2/drug effects ; *COVID-19/epidemiology/virology/prevention & control ; Aged ; Leucine/therapeutic use ; Antiviral Agents/therapeutic use ; Outpatients ; Drug Therapy, Combination ; Proline/analogs & derivatives/therapeutic use ; Lactams ; Nitriles ; }, abstract = {Nirmatrelvir plus ritonavir received Emergency Use Authorization for treating mild to moderate COVID-19 in high-risk patients. Its efficacy against the Omicron variant of SARS-CoV-2 remains uncertain. This retrospective cohort study assessed the effect of nirmatrelvir-ritonavir in preventing severe disease progression and long COVID symptoms after acute COVID-19 in non-hospitalized adults. SALAMA medical records from Dubai's COVID-19 healthcare centers between May 22, 2022, and April 30, 2023, were used to identify 7290 eligible patients, 9.6% of whom received nirmatrelvir-ritonavir. Treatment was associated with a notable reduction in COVID-19-related hospitalizations (adjusted hazard ratio [HR] of 0.39; 95% CI, 0.18-0.85) by day 28 of symptom onset. Moreover, nirmatrelvir-ritonavir was associated with fewer long COVID symptoms (adjusted HR of 0.42; 95% CI, 0.19-0.95). This suggests the significant effectiveness of nirmatrelvir-ritonavir against the Omicron variant, reducing both severe and long-term COVID-19 symptoms.}, } @article {pmid39472233, year = {2024}, author = {Guidry, JPD and Laestadius, LI and Burton, CW and Miller, CA and Perrin, PB and Campos-Castillo, C and Chelimsky, T and Gharbo, R and Carlyle, KE}, title = {Patient-provider relationships and long COVID: A cross-sectional survey about impact on quality of life.}, journal = {Disability and health journal}, volume = {}, number = {}, pages = {101722}, doi = {10.1016/j.dhjo.2024.101722}, pmid = {39472233}, issn = {1876-7583}, abstract = {BACKGROUND: In the United States (U.S.), it is estimated that 17.6 % of adults have experienced Long COVID, a condition where symptoms newly develop and linger after initial COVID-19 infection. Long COVID is associated with significantly reduced quality of life (QoL), and patient-provider relationships have been shown to influence QoL for patients in general.

OBJECTIVE: The objective for this study was to better understand the role of patient-provider relationships in shaping QoL among U.S. adults with Long COVID.

METHODS: This study carried out an online survey among U.S. adult with Long COVID (N = 792).

RESULTS: Respondents with at least a bachelor's degree reported higher QoL, and older respondents were more likely to report lower QoL; trust in providers was a significant predictor of higher QoL, while dismissal of Long COVID symptoms was associated with lower QoL (all p < .05).

CONCLUSIONS: Healthcare providers should be aware of the importance of trust in the relationship with their Long COVID patients and the impact this may have on patients' QoL. Researchers and policy makers should include an increasing focus on training for providers who treat patients with Long COVID in order to strengthen patient-provider relationships.}, } @article {pmid39471195, year = {2024}, author = {Aldhawyan, AF and BuSaad, MA and Alamri, BA and Alsaihati, MI and Alanazi, BS and Alanazi, RA and Bahamdan, AS}, title = {Evaluating the Predictors of Persistent Long COVID Symptoms and Their Severity in COVID-19 Survivors 1 Year After Infection.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241295686}, pmid = {39471195}, issn = {2150-1327}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; Saudi Arabia/epidemiology ; *Survivors ; Adult ; *Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Aged ; SARS-CoV-2 ; Alopecia/epidemiology ; Young Adult ; Memory Disorders/etiology/epidemiology ; }, abstract = {INTRODUCTION/OBJECTIVE: As the coronavirus disease 2019 (COVID-19) pandemic progressed, the virus was found to cause long-term health complications known as long COVID (LC). This study aimed to investigate LC symptom severity and the factors associated with the likelihood of persistence beyond 1 year among COVID-19 survivors in Saudi Arabia.

METHODS: This descriptive, cross-sectional, questionnaire-based study was conducted via convenience sampling between December 1, 2023, and March 1, 2024. In-person interviews were performed, and 845 individuals with persistent symptoms after acute COVID-19 were included.

RESULTS: Hair loss and memory impairment were the most reported symptoms. In predicting LC persistence beyond 12 months, women were found to have higher odds of being symptomatic than men, and individuals from moderate-to-high-income households were more likely to report persistent symptoms than those from low-income households. Each additional acute COVID-19 symptom increased the likelihood of persistent symptoms by 1.14 times. Reporting more symptoms in the first 6 months post-infection significantly reduced the odds of long-term symptoms by approximately 30%.

CONCLUSION: LC symptom severity varies among patients, and sociodemographic and clinical factors influence the likelihood of experiencing symptoms beyond 1 year. Understanding these factors can provide insights and help optimize management, leading to improved patient outcomes.}, } @article {pmid39469684, year = {2024}, author = {Vergori, A and Del Duca, G and Borrelli, P and Brita, AC and Pinnetti, C and Mastrorosa, I and Camici, M and Mondi, A and Mazzotta, V and Chinello, P and Mencarini, P and Giancola, ML and Abdeddaim, A and Girardi, E and Antinori, A}, title = {Cognitive outcomes and psychological symptoms in an Italian cohort with post-acute COVID-19 condition (PACC).}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e39431}, pmid = {39469684}, issn = {2405-8440}, abstract = {BACKGROUND: We aim to investigate the proportion of patients (pts) with long-term cognitive outcomes (CO) of PACC and identify associated features.

METHODS: We assessed participants through a neuropsychological assessment. The chi-square test was used for comparisons according with time of NPA (within or beyond 6 months since COVID19) and with previously hospitalization status (hospitalized patients, PH; not hospitalized patients, nPH).

RESULTS: 520 participants: mean age 54 years (SD 12), 53 % female, 14 years of education (SD 3.4), 35 % with >1 comorbidity, 48 % previously hospitalized. Overall, we found CO in 89 % of pts, in particular 88 % evaluated in w6M and 89 % in b6M (p = 0.801) while 90 % and 87 % in nPH and PH, respectively (p = 0.239). By fitting multivariable analysis, PH for COVID19 and female gender were associated with an increased risk of an altered PSQI [Odd Ratio, OR 2.48, 95 % CI 1.54 to 3.99, p < 0.001 and OR 2.59, 95 % CI 1.60 to 4.17, p < 0.001, respectively) and BAI [F vs M: OR 1.67, 95 % CI 1.16 to 2.40, p = 0.005).

CONCLUSIONS: We show a substantial proportion of PACC-CO; hospitalization leads to impaired memory, anxiety and sleep disorders. Women seem to be at higher risk for anxious-depressive symptoms and worse sleep quality than men.}, } @article {pmid39469144, year = {2024}, author = {Li, T and He, B and Liu, Y and Wang, C}, title = {Accumulated subcutaneous fat in abdomen is associated with long COVID-19 symptoms among non-hospitalized patients: a prospective observational study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1410559}, pmid = {39469144}, issn = {2296-858X}, abstract = {INTRODUCTION: Long COVID-19 symptoms may have a variety of potential overlapping causes. In this study, we aimed to investigate the potential correlation between abdominal adipose tissue and long COVID-19 symptoms in non-hospitalized patients in China.

METHODS: This is a prospective observational study. 424 subjects, recovered from COVID-19 for 2-4 weeks, were enrolled and 408 subjects were finished the follow-up investigation at baseline, 8[th] week and 12[th] week. Physical measurements were collected. Kaplan-Meier analysis and cox regression analysis were carried out to assess the correlation.

RESULTS: A total of 72 subjects reported the long COVID-19 symptoms. The adjusted Kaplan-Meier analysis and Cox regression analysis revealed a significant correlation with accumulated subcutaneous fat (SFA ≥ 2.0 dm[2]) and the long COVID-19 symptoms (HR = 2.63, P < 0.001 for male, HR = 1.52, P = 0.048 for female). However, overweight and central obesity showed positive correlation only in women.

DISCUSSION: This study suggested that accumulated subcutaneous fat in abdomen (SFA ≥ 2.0 dm[2]) was an important positive factor associated with long COVID-19 symptoms among Chinese non-hospitalized patients. Large investigation and prospective studies are needed to validate the correlation in the future.}, } @article {pmid39468707, year = {2024}, author = {Zhou, D and Luo, Y and Ma, Q and Xu, Y and Yao, X}, title = {The characteristics of TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients.}, journal = {Virulence}, volume = {15}, number = {1}, pages = {2421987}, pmid = {39468707}, issn = {2150-5608}, mesh = {Humans ; *COVID-19/immunology/prevention & control ; *Complementarity Determining Regions/genetics/immunology ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology/genetics ; *Receptors, Antigen, T-Cell/immunology/genetics ; T-Lymphocytes/immunology ; High-Throughput Nucleotide Sequencing ; }, abstract = {The COVID-19 pandemic and large-scale administration of multiple SARS-CoV-2 vaccines have attracted global attention to the short-term and long-term effects on the human immune system. An analysis of the "traces" left by the body's T-cell immune response is needed, especially for the prevention and treatment of breakthrough infections and long COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections. T-cell receptor complementarity determining region 3 (TCR CDR3) repertoire serves as a target molecule for monitoring the effects, mechanisms, and memory of the T-cell response. Furthermore, it has been extensively applied in the elucidation of the infectious mechanism and vaccine refinement of hepatitis B virus (HBV), influenza virus, human immunodeficiency virus (HIV), and SARS-CoV. Laboratories worldwide have utilized high-throughput sequencing (HTS) and scTCR-seq to characterize, share, and apply the TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients. This article focuses on the comparative analysis of the diversity, clonality, V&J gene usage and pairing, CDR3 length, shared CDR3 sequences or motifs, and other characteristics of TCR CDR3 repertoire. These findings provide molecular targets for evaluating T-cell response effects and short-term and long-term impacts on the adaptive immune system following SARS-CoV-2 infection or vaccination and establish a comparative archive of T-cell response "traces."}, } @article {pmid39468090, year = {2024}, author = {Wilk, P and Cuschieri, S}, title = {Effect of the COVID-19 pandemic on the well-being of middle-aged and older Europeans.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25796}, pmid = {39468090}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology/psychology ; Europe/epidemiology ; European People ; Longitudinal Studies ; Pandemics ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome/epidemiology/psychology ; *Psychological Well-Being ; }, abstract = {The COVID-19 pandemic has been associated with a general decline in well-being. However, there is limited evidence on the effect of the pandemic on the general population, and especially among the ageing population. We assessed the overall impact of the pandemic on the well-being of middle-aged and older adults residing in 27 European countries, focusing on the time-period before summer 2021. We used a sample of 46,209 respondents from the two population-based longitudinal Corona Surveys collected during summer 2020 and summer 2021. To test our hypotheses, we used latent change score models. All analyses were stratified by sex. The COVID-19 pandemic affected middle-aged and older Europeans' well-being irrespective of their sex. Being infected by the COVID-19 virus at the start of the pandemic had a negative impact on well-being. As expected, adults with Long COVID experienced the most pronounced decline in well-being. A novel finding was the decline in the level of well-being among adults not infected by the COVID-19 virus. Support should be provided at community levels with specific attention towards individuals with Long COVID symptoms and those infected with COVID-19 at earlier stages of the pandemic.}, } @article {pmid39465803, year = {2024}, author = {Xiao, N and Xiao, J and Tang, Q and Pan, G and Wei, K and Zhao, H and Wang, J}, title = {Is detrusor underactivity the urodynamic characteristic of long-COVID in patients with benign prostate hyperplasia?.}, journal = {Medicine}, volume = {103}, number = {41}, pages = {e40156}, pmid = {39465803}, issn = {1536-5964}, support = {2021SK52002//Planned projects of Guiding technological innovation of Hunan Province/ ; 20210218-2//Guilin Science and Technology Development Program/ ; S2020105//Scientific Research Project of Guangxi Health Commission/ ; }, mesh = {Humans ; Male ; *Prostatic Hyperplasia/complications/physiopathology ; *COVID-19/complications/physiopathology ; *Urodynamics ; Aged ; Middle Aged ; *Urinary Bladder, Underactive/physiopathology/etiology ; *Ultrasonography/methods ; Urinary Bladder/physiopathology/diagnostic imaging ; SARS-CoV-2 ; Retrospective Studies ; }, abstract = {Although coronavirus disease 19 (COVID-19) was reported to involve with multiple organs, COVID-19 reports focusing on urinary system mostly evaluated the association between lower urinary tract symptoms and COVID-19 using questionnaire score. In this study, sonography video urodynamic studies was first conducted to explore the effects of COVID-19 on contractility of bladder detrusor of patients with benign prostate hyperplasia (BPH). Clinical data was respectively reviewed and compared between BPH patients with previous COVID-19 infection (COVID-19 group) and without previous COVID-19 (non-COVID-19 group). The incidence of detrusor underactivity (DU) was compared between 2 groups. Comparison of age and noninvasive parameters was conducted between BPH patients with DU and without DU in COVID-19 group. Correlation coefficient between noninvasive parameters and detrusor contractility was determined and receiver operating characteristic curve of noninvasive parameters was used to choose the most appropriate cutoff for detection of DU in COVID-19 group. Beside a significant increase in the incidence of DU in BPH patients of COVID-19 group, a lower detrusor contractility and a greater bladder wall thick was detected compared to that of patients in non-COVID-19 group. Post-voiding residual urine was found to have a linear correlation with detrusor contractility in COVID-19 group. It was suggested that COVID-19 infection would further exacerbate impairment of detrusor previously resulted from bladder outlet obstruction in BPH patients. DU may be a urodynamic characteristic of long-COVID.}, } @article {pmid39464351, year = {2024}, author = {Sharma, A and Jakhar, RK and Kakkar, V and Singal, G}, title = {Persistent ENT Manifestations in Individuals who Recovered from COVID-19: A Systematic Review.}, journal = {International archives of otorhinolaryngology}, volume = {28}, number = {4}, pages = {e697-e701}, pmid = {39464351}, issn = {1809-9777}, abstract = {Introduction Long coronavirus disease (COVID) refers to the persistence of symptoms long after the recovery from the acute phase of the illness, and it is due to the interplay of various inflammatory mechanisms. This has led to emergence of new deficits, including otorhinolaryngological symptoms, in patients wo have recovered from COVID. The plethora of otorhinolaryngological symptoms associated with long COVID are tinnitus, sensorineural hearing loss (SNHL), vertigo, nasal congestion, sinonasal discomfort, hyposmia/anosmia, dysgeusia, sore throat, dry cough, dyspnea, dysphagia, and hoarseness of voice. Objective To evaluate the possible ENT symptoms in patients wo have recovered from COVID and to combine those findings with our experience. Data Synthesis We conducted a search on the PubMed, ENT Cochrane, Web of Science, and Google Scholar databases, and a total of 44 studies were selected for the present review. Conclusion Otorhinolaryngological complications such as tinnitus, SNHL, vertigo, nasal congestion, sinonasal discomfort, hyposmia/anosmia, dysgeusia, sore throat, dry cough, dyspnea, dysphagia, and hoarseness of voice have been widely reported among in long-COVID patients.}, } @article {pmid39459851, year = {2024}, author = {Mohammed, I and Podhala, S and Zamir, F and Shiyam, S and Salameh, AR and Salahuddin, Z and Salameh, H and Kim, C and Sinan, Z and Kim, J and Al-Abdulla, D and Laws, S and Mushannen, M and Zakaria, D}, title = {Gastrointestinal Sequelae of COVID-19: Investigating Post-Infection Complications-A Systematic Review.}, journal = {Viruses}, volume = {16}, number = {10}, pages = {}, pmid = {39459851}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; *Gastrointestinal Diseases/etiology/virology ; *SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Pancreatitis/complications/etiology ; Gastrointestinal Tract/virology/pathology ; Colitis, Ulcerative/complications ; }, abstract = {Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized. These complications range from severe acute pancreatitis to colitis, adding complexity to diagnosis and management. A comprehensive database search was conducted using several databases. Our inclusion criteria encompassed studies reporting severe and long-term GI complications of COVID-19. Digestive disorders were categorized into infections, inflammatory conditions, vascular disorders, structural abnormalities, other diagnoses, and undiagnosed conditions. Of the 73 studies that were selected for full-text review, only 24 met our inclusion criteria. The study highlights a broad range of gastrointestinal complications following COVID-19 infection (excluding liver complications, which are examined separately), including inflammatory conditions, such as ulcerative colitis (UC), acute pancreatitis, and multisystem inflammatory syndrome in children (MIS-C). Other GI complications were reported such as vascular disorders, including diverse thrombotic events and structural abnormalities, which ranged from bowel perforations to adhesions. Additionally, undiagnosed conditions like nausea and abdominal pain were prevalent across different studies involving 561 patients. The findings emphasize the substantial impact of COVID-19 on the GI tract. Ongoing research and monitoring are crucial to understanding the long-term effects and developing effective management strategies for these complications.}, } @article {pmid39459041, year = {2024}, author = {Umsumarng, S and Dissook, S and Arjsri, P and Srisawad, K and Thippraphan, P and Sangphukieo, A and Thongkumkoon, P and Dejkriengkraikul, P}, title = {Inhibitory Effect of Luteolin on Spike S1 Glycoprotein-Induced Inflammation in THP-1 Cells via the ER Stress-Inducing Calcium/CHOP/MAPK Pathway.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {10}, pages = {}, pmid = {39459041}, issn = {1424-8247}, support = {FF063/2567//the Fundamental Fund 2024, Chiang Mai University, Thailand./ ; }, abstract = {BACKGROUND/OBJECTIVES: The global SARS-CoV-2 outbreak has escalated into a critical public health emergency, with the spike glycoprotein S1 subunit of SARS-CoV-2 (spike-S1) linked to inflammation in lung tissue and immune cells. Luteolin, a flavone with anti-inflammatory properties, shows promise, but research on its effectiveness against long-COVID-related inflammation and spike protein-induced responses remains limited. This study aims to elucidate the underlying mechanisms of inflammation in THP-1 cells induced by the spike-S1. Additionally, it seeks to assess the potential of luteolin in mitigating inflammatory responses induced by the spike-S1 in a THP-1 macrophage model.

METHODS: The gene expression profiles of spike-S1 in THP-1 cells were analyzed by transcriptome sequencing. The inhibitory effect of luteolin on ER stress and inflammation in spike-S1-induced THP-1 cells was investigated using Western blotting, RT-PCR, and ELISA.

RESULTS: The candidate genes (CAMK2A, SIGLEC7, PPARGC1B, SEC22B, USP28, IER2, and TIRAP) were upregulated in the spike-S1-induced THP-1 group compared to the control group. Among these, calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) was identified as the most promising molecule in spike-S1-induced THP-1 cells. Our results indicate that the spike S1 significantly increased the expression of ER-stress markers at both gene and protein levels. Luteolin significantly reduced ER stress by decreasing the expression of ER-stress marker genes and ER-stress marker proteins (p < 0.01). Additionally, luteolin exhibited anti-inflammatory properties upon spike S1-induction in THP-1 cells by significantly suppressing IL-6, IL-8, and IL-1β cytokine secretion in a dose-dependent manner (p < 0.05). Furthermore, our results revealed that luteolin exhibited the downregulation of the MAPK pathway, as evidenced by modulating the phosphorylation of p-ERK1/2, p-JNK and p-p38 proteins (p < 0.05).

CONCLUSIONS: The results from this study elucidate the mechanisms by which the spike S1 induces inflammation in THP-1 cells and supports the use of naturally occurring bioactive compounds, like luteolin, against inflammation-related SARS-CoV-2 infection.}, } @article {pmid39458187, year = {2024}, author = {Maritescu, A and Crisan, AF and Pescaru, CC and Stoicescu, ER and Oancea, C and Iacob, D}, title = {Effectiveness of Combined Pulmonary Rehabilitation and Progressive Muscle Relaxation in Treating Long-Term COVID-19 Symptoms: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {13}, number = {20}, pages = {}, pmid = {39458187}, issn = {2077-0383}, abstract = {Background: The aim of this study was to investigate the effects of pulmonary rehabilitation (PR) and additional progressive muscle relaxation (PMR) techniques in patients with long-term COVID-19 symptoms. Methods: We included 61 patients with long COVID-19 symptoms and randomly assigned them to two groups: PR only (group 1 with 30 subjects) and PR with PMR (group 2 with 31 subjects). The PR program consisted of gradual aerobic conditioning, strength training, and breathing exercises. Group 2 received additional 20 min daily sessions of progressive muscle relaxation techniques. Results: Following a 21-day intervention, it was observed that both groups had noteworthy improvements in lung function, exercise capacity, and sleep quality with statistical significance (p < 0.0001). Group 2 showed significant improvements in overall health (as measured by the General Health Questionnaire-12), patient health (as assessed by the Patient Health Questionnaire-9), general anxiety levels (as indicated by the Generalized Anxiety Disorders Scale-7), and sleep quality (as measured by the Pittsburgh Sleep Quality Index), with statistical significance (p < 0.0001), compared to group 1. Moreover, the statistical analysis demonstrated no significant difference in exercise capacity improvement between group 1 and group 2, as indicated by a p-value of 0.1711. Conclusions: The addition of progressive muscle relaxation to pulmonary rehabilitation significantly enhances mental health outcomes, particularly in reducing anxiety and improving sleep quality, for patients with long-term COVID-19 symptoms. These findings suggest that incorporating PMR into PR programs offers a valuable non-pharmacological approach to improving overall patient well-being during long-term COVID-19 recovery.}, } @article {pmid39457567, year = {2024}, author = {Mauro, M and Zulian, E and Bestiaco, N and Polano, M and Larese Filon, F}, title = {Slow-Paced Breathing Intervention in Healthcare Workers Affected by Long COVID: Effects on Systemic and Dysfunctional Breathing Symptoms, Manual Dexterity and HRV.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457567}, issn = {2227-9059}, support = {FRA 2022//University of Trieste/ ; }, abstract = {BACKGROUND: Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention.

METHODS: 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments.

RESULTS: After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.}, } @article {pmid39457358, year = {2024}, author = {Cunha, ACR and Silva, JC and Garcês, CP and Sisconeto, TM and Nascimento, JLR and Amaral, AL and Cunha, TM and Mariano, IM and Puga, GM}, title = {Online and Face-to-Face Mat Pilates Training for Long COVID-19 Patients: A Randomized Controlled Trial on Health Outcomes.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {10}, pages = {}, pmid = {39457358}, issn = {1660-4601}, support = {CNPq 404549/2021-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; *COVID-19 ; Male ; Female ; Middle Aged ; *Exercise Movement Techniques/methods ; SARS-CoV-2 ; Fatigue ; Body Composition ; Muscle Strength ; Adult ; }, abstract = {This study investigated the impacts of online and face-to-face Mat Pilates training in adults with persistent symptoms of long COVID on health outcomes. Forty-nine patients (52 ± 5.85 yr.) diagnosed with long COVID related to fatigue symptoms were randomly included in three groups: online Mat Pilates training (n = 16), face-to-face Mat Pilates training (n = 15), and a control group (n = 18) without training. Mat Pilates training was conducted three times a week for 12 weeks. Fatigue, functional capacity, anthropometrics, body composition, and cardiometabolic markers were assessed before and after the interventions. Two-factor Generalized Estimating Equation analyses identified significant differences with Bonferroni post hoc testing (p < 0.05). After the intervention, only the face-to-face Mat Pilates training group had an improved total, physical and mental fatigue, trunk isometric strength, upper limb muscle endurance strength, and aerobic capacity (p < 0.05). No changes were found in fat mass, muscle mass, free fat mass, % of fat, body mass, body mass index, or waist and hip circumferences. No significant changes were observed in blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, or blood pressure (p > 0.05). Our results highlight the potential of face-to-face Mat Pilates training as an effective intervention to mitigate persistent symptoms of long COVID related to fatigue and functional capacities.}, } @article {pmid39457356, year = {2024}, author = {Graham, EL and D'Isabel, S and Lofrano-Porto, A and Smith, DL}, title = {Musculoskeletal, Pulmonary, and Cardiovascular COVID-19 Sequelae in the Context of Firefighter Occupational Health: A Narrative Review.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {10}, pages = {}, pmid = {39457356}, issn = {1660-4601}, support = {EMW-2020-FP-00243//Federal Emergency Management Agency/ ; }, mesh = {Humans ; *COVID-19/complications ; *Firefighters ; Occupational Health ; SARS-CoV-2 ; Cardiovascular Diseases/etiology ; Musculoskeletal Diseases/etiology/virology ; Lung Diseases/etiology/physiopathology/virology ; }, abstract = {For most individuals infected with SARS-CoV-2, the acute illness resolves completely. However, for millions of people, symptoms or sequelae from COVID-19 recur or persist for months to years after infection. Post-COVID-19 sequelae are wide-ranging, often affecting the musculoskeletal, pulmonary, and cardiovascular systems. All who experience post-COVID-19 sequelae face significant challenges navigating home and work life. Occupations such as firefighting, however, are of particular concern given the strenuous nature of a job that relies on a healthy musculoskeletal, pulmonary, and cardiovascular system. Research has documented significant musculoskeletal impairment (including muscle weakness, pain, and fatigue), respiratory dysfunction (including reduced lung function, interstitial disease, and diffusion abnormalities), cardiovascular conditions (including cardiac events, ischemic disease, dysrhythmias, and infectious diseases), and diminished cardiorespiratory fitness that continues for months to years in some individuals. These persistent post-COVID-19 conditions may affect a firefighter's ability to return to work, function at full capacity while at work, and potentially compromise firefighter health and public safety. This review, therefore, explores musculoskeletal, pulmonary, and cardiovascular sequelae post-COVID-19 and the impact of these sequelae on firefighter health and occupational readiness.}, } @article {pmid39457266, year = {2024}, author = {Goulart, CDL and Arêas, GPT and Milani, M and Borges, FFDR and Magalhães, JR and Back, GD and Borghi-Silva, A and Oliveira, LFL and de Paula, AR and Marinho, CC and Prado, DP and Almeida, CN and Dias, CMCC and Gomes, VA and Ritt, LEF and Franzoni, LT and Stein, R and Neto, MG and Cipriano Junior, G and Almeida-Val, F}, title = {Sex-Based Differences in Pulmonary Function and Cardiopulmonary Response 30 Months Post-COVID-19: A Brazilian Multicentric Study.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {10}, pages = {}, pmid = {39457266}, issn = {1660-4601}, mesh = {Humans ; Female ; *COVID-19/physiopathology ; Male ; Brazil ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Respiratory Function Tests ; Sex Factors ; Muscle Strength ; Respiratory Muscles/physiopathology ; Cardiorespiratory Fitness/physiology ; Exercise Test ; SARS-CoV-2 ; Lung/physiopathology ; }, abstract = {Aim: (I) to verify if there are sex differences in respiratory function, respiratory muscle strength, and effort limitation in individuals recovered from severe acute COVID-19 30 months after the initial infection, and (II) to evaluate the influence of length of stay on cardiorespiratory capacity among men and women. Methods: Cross-sectional observational multicentric study with participants from five Brazilian states (São Paulo, Amazonas, Minas Gerais, Bahia, and Brasília). We assessed lung function and respiratory muscle strength by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and cardiorespiratory fitness by cardiopulmonary exercise test (CPET). Results: 86 individuals were stratified by sex (48 women and 38 men). Females had significantly longer hospitalization for acute COVID-19 (p < 0.05) and showed a marked reduction in MIP (cmH2O and % predicted). Regarding the CPET, women presented lower V˙O2% predicted, O2 pulse, and oxygen uptake efficiency slope (OUES, % predicted) (p < 0.05). In addition, women also had greater abnormal combinations between RER < 1.10, OUES < 80% predicted, VE/VVM < 15% [3 (6.2%)] and V˙O2% predicted < 80%, V˙E/V˙CO2 slope and V˙O2/workload < 8.4 mL/min/W [8 (17%)]. The regression analysis showed a significant influence of age, length of hospitalization (< and >10 days), and FEV1/FVC (%) on the V˙O2 peak (mL·kg[-1]·min[-1]). Secondarily, we found that women hospitalized for more than 10 days had worse O2 pulse (p = 0.03), OUES % predicted (p < 0.001), and worse V˙O2% predicted (p < 0.009). Conclusion: Women exhibited more pronounced impairments in several key indicators of cardiopulmonary function 30 months post-infection.}, } @article {pmid39456822, year = {2024}, author = {Papadopoulou, P and Polissidis, A and Kythreoti, G and Sagnou, M and Stefanatou, A and Theoharides, TC}, title = {Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, Olea europaea L., in Long COVID and Other Conditions Involving Cognitive Impairment.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39456822}, issn = {1422-0067}, mesh = {*Olea/chemistry ; *Polyphenols/pharmacology/therapeutic use/chemistry ; Humans ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Cognitive Dysfunction/drug therapy ; *Anti-Inflammatory Agents/pharmacology/therapeutic use/chemistry ; *COVID-19 ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects ; Animals ; Plant Extracts/pharmacology/therapeutic use/chemistry ; Alzheimer Disease/drug therapy ; }, abstract = {The European olive tree, Olea europaea L., and its polyphenols hold great therapeutic potential to treat neuroinflammation and cognitive impairment. This review examines the evidence for the anti-inflammatory and neuroprotective actions of olive polyphenols and their potential in the treatment of long COVID and neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Key findings suggest that olive polyphenols exhibit antioxidant, anti-inflammatory, neuroprotective, and antiviral properties, making them promising candidates for therapeutic intervention, especially when formulated in unique combinations. Recommendations for future research directions include elucidating molecular pathways through mechanistic studies, exploring the therapeutic implications of olive polyphenol supplementation, and conducting clinical trials to assess efficacy and safety. Investigating potential synergistic effects with other agents addressing different targets is suggested for further exploration. The evidence reviewed strengthens the translational value of olive polyphenols in conditions involving cognitive dysfunction and emphasizes the novelty of new formulations.}, } @article {pmid39456253, year = {2024}, author = {Gopalaswamy, R and Aravindhan, V and Subbian, S}, title = {The Ambivalence of Post COVID-19 Vaccination Responses in Humans.}, journal = {Biomolecules}, volume = {14}, number = {10}, pages = {}, pmid = {39456253}, issn = {2218-273X}, mesh = {Humans ; 2019-nCoV Vaccine mRNA-1273/immunology ; BNT162 Vaccine/immunology ; *COVID-19/prevention & control ; *COVID-19 Vaccines/adverse effects/immunology ; Vaccination ; }, abstract = {The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases of clinical trials and include the whole virus or its parts like DNA, mRNA, or protein subunits administered directly or through vectors. Beginning in 2020, a few mRNA (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and adenovirus-based (AstraZeneca ChAdOx1-S and the Janssen Ad26.COV2.S) vaccines were recommended by WHO for emergency use before the completion of the phase 3 and 4 trials. These vaccines were mostly administered in two or three doses at a defined frequency between the two doses. While these vaccines, mainly based on viral nucleic acids or protein conferred protection against the progression of SARS-CoV-2 infection into severe COVID-19, and prevented death due to the disease, their use has also been accompanied by a plethora of side effects. Common side effects include localized reactions such as pain at the injection site, as well as systemic reactions like fever, fatigue, and headache. These symptoms are generally mild to moderate and resolve within a few days. However, rare but more serious side effects have been reported, including allergic reactions such as anaphylaxis and, in some cases, myocarditis or pericarditis, particularly in younger males. Ongoing surveillance and research efforts continue to refine the understanding of these adverse effects, providing critical insights into the risk-benefit profile of COVID-19 vaccines. Nonetheless, the overall safety profile supports the continued use of these vaccines in combating the pandemic, with regulatory agencies and health organizations emphasizing the importance of vaccination in preventing COVID-19's severe outcomes. In this review, we describe different types of COVID-19 vaccines and summarize various adverse effects due to autoimmune and inflammatory response(s) manifesting predominantly as cardiac, hematological, neurological, and psychological dysfunctions. The incidence, clinical presentation, risk factors, diagnosis, and management of different adverse effects and possible mechanisms contributing to these effects are discussed. The review highlights the potential ambivalence of human response post-COVID-19 vaccination and necessitates the need to mitigate the adverse side effects.}, } @article {pmid39455598, year = {2024}, author = {Martins, SM and Adams, R and Rodrigues, EM and Stelmach, R and Adab, P and Chi, C and Cheng, KK and Cooper, BG and Correia-de-Sousa, J and Dickens, AP and Enocson, A and Farley, A and Gale, N and Jolly, K and Jordan, RE and Jowett, S and Maglakelidze, M and Maghlakelidze, T and Sitch, A and Stavrikj, K and Turner, AM and Williams, S and Nascimento, VB}, title = {Living with COPD and its psychological effects on participating in community-based physical activity in Brazil: a qualitative study. Findings from the Breathe Well group.}, journal = {NPJ primary care respiratory medicine}, volume = {34}, number = {1}, pages = {33}, pmid = {39455598}, issn = {2055-1010}, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/psychology/therapy ; Male ; Female ; *Exercise/psychology ; *COVID-19/psychology/epidemiology/prevention & control ; Brazil ; *Qualitative Research ; Middle Aged ; Aged ; *Quality of Life ; Depression/psychology ; Anxiety/psychology ; SARS-CoV-2 ; Health Knowledge, Attitudes, Practice ; Adult ; }, abstract = {Physical activity (PA) improves dyspnoea, psychological wellbeing and quality of life (QoL) for people with COPD reducing their risk of exacerbation. However, engagement in PA is low especially amongst those with anxiety and depression, and PA programmes are limited in countries with limited resources such as Brazil. We explored perceptions of 21 people with COPD about the impact of their disease on taking part in community-based PA programmes in Sao Paulo, Brazil through semi-structured telephone interviews from October 2020 to April 2021. Discussions were audio-recorded, transcribed, and analysed using the Framework method. Five themes were identified: Knowledge about COPD and its management; Self-perception of life with COPD; Knowledge and experiences of depression and anxiety; Opinions on PA and repercussions of COVID-19. PA was considered to be important in bringing physical and mental health benefits but there were barriers in accessibility of formal PR programmes and therefore local community PA programmes were considered to be important. People with mental health conditions tended to view PA more negatively. COVID-19 had reduced PA opportunities, access to COPD treatment and social interaction, and was associated with more exacerbations and emotional suffering. In general, this study showed an urgent need to improve knowledge about COPD and its risk factors and management among both patients, the public and primary healthcare professionals. We provide important content for the formulation of public policies for the implementation of specific activity programmes for people with COPD in community spaces using local resources and intersectoral partnerships.}, } @article {pmid39455248, year = {2024}, author = {Burnett, DM}, title = {Supporting Evidence For Pulmonary Rehabilitation in the Treatment of Long COVID.}, journal = {Respiratory care}, volume = {69}, number = {11}, pages = {1477-1479}, pmid = {39455248}, issn = {1943-3654}, } @article {pmid39454992, year = {2024}, author = {Yu, LC}, title = {Gastrointestinal pathophysiology in long COVID: Exploring roles of microbiota dysbiosis and serotonin dysregulation in post-infectious bowel symptoms.}, journal = {Life sciences}, volume = {358}, number = {}, pages = {123153}, doi = {10.1016/j.lfs.2024.123153}, pmid = {39454992}, issn = {1879-0631}, mesh = {Animals ; Humans ; *Dysbiosis/metabolism/microbiology/physiopathology/virology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology/physiopathology/virology ; *Irritable Bowel Syndrome/physiopathology/microbiology/metabolism/virology ; *Post-Acute COVID-19 Syndrome/metabolism/microbiology/physiopathology/virology ; SARS-CoV-2 ; *Serotonin/metabolism ; }, abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.}, } @article {pmid39454250, year = {2024}, author = {Tebeka, S and Coste, J and Makovski, TT and Alleaume, C and Delpierre, C and Gallay, A and Pignon, B and Gouraud, C and Ouazana Vedrines, C and Pitron, V and Robineau, O and Steichen, O and Lemogne, C}, title = {Dissecting the association between long COVID and depressive symptoms in a nationally representative population from France.}, journal = {Journal of psychosomatic research}, volume = {187}, number = {}, pages = {111961}, doi = {10.1016/j.jpsychores.2024.111961}, pmid = {39454250}, issn = {1879-1360}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/psychology ; Middle Aged ; Cross-Sectional Studies ; France/epidemiology ; Adult ; *Post-Acute COVID-19 Syndrome ; *Depression/epidemiology ; Prevalence ; SARS-CoV-2 ; Aged ; Depressive Disorder, Major/epidemiology ; }, abstract = {OBJECTIVE: Depressive symptoms may overlap with those of long COVID. This cross-sectional study aims to compare the prevalence of depressive symptoms among individuals infected with SARS-CoV-2 with versus without long COVID and to explore specific associations with each of the nine core symptoms of major depression.

METHODS: Data regarding age, gender, SARS-CoV-2 infections, current symptoms, their date of onset, impact on daily functioning, and consideration of alternative diagnoses were collected through phone interviews between September and December 2022 in a nationally representative sample of adults aged ≥18. Data on chronic health conditions and depressive symptoms (PHQ-9) were collected online in infected participants with or without long COVID, according to the WHO definition of the post-COVID-19 condition.

RESULTS: Among 1247 participants (mean age (SD): 48.3 (14.3) years, 53.3 % of women), 12.8 % had long COVID and 87.2 % experienced SARS-CoV-2 infection at least 3 months prior to the survey without long COVID. Participant with long COVID were four-fold more likely to have a PHQ-9 score ≥ 10 than those without (44.0 % versus 11.1 %). Three symptoms out of nine were independently associated with long COVID: little interest or pleasure (aOR [95 % CI]: 2.01 [1.03-3.92]), feeling tired or having little energy (1.92 [1.10-3.33]), and poor attention/concentration (2.02 [1.03-3.96]).

CONCLUSION: Clinicians should screen patients with long COVID for major depression but associations with specific depressive symptoms suggest some clinical overlap. Future studies should consider the course of each depressive symptom separately and focus on those less prone to overlap with symptoms of long COVID.}, } @article {pmid39451987, year = {2024}, author = {Costanza, A and Amerio, A and Aguglia, A and Rossi, M and Parise, A and Magnani, L and Serafini, G and Amore, M and Martins, D and Nguyen, KD}, title = {Reactive Astrocytosis-A Potential Contributor to Increased Suicide in Long COVID-19 Patients?.}, journal = {Brain sciences}, volume = {14}, number = {10}, pages = {}, pmid = {39451987}, issn = {2076-3425}, abstract = {BACKGROUND: Long COVID-19 is an emerging chronic illness of significant public health concern due to a myriad of neuropsychiatric sequelae, including increased suicidal ideation (SI) and behavior (SB).

METHODS: This review provides a concise synthesis of clinical evidence that points toward the dysfunction of astrocytes, the most abundant glial cell type in the central nervous system, as a potential shared pathology between SI/SB and COVID-19.

RESULTS: Depression, a suicide risk factor, and SI/SB were both associated with reduced frequencies of various astrocyte subsets and complex proteomic/transcriptional changes of astrocyte-related markers in a brain-region-specific manner. Astrocyte-related circulating markers were increased in depressed subjects and, to a less consistent extent, in COVID-19 patients. Furthermore, reactive astrocytosis was observed in subjects with SI/SB and those with COVID-19.

CONCLUSIONS: Astrocyte dysfunctions occurred in depression, SI/SB, and COVID-19. Reactive-astrocyte-mediated loss of the blood-brain barrier (BBB) integrity and subsequent neuroinflammation-a factor previously linked to SI/SB development-might contribute to increased suicide in individuals with long COVID-19. As such, the formulation of new therapeutic strategies to restore astrocyte homeostasis, enhance BBB integrity, and mitigate neuroinflammation may reduce SI/SB-associated neuropsychiatric manifestations among long COVID-19 patients.}, } @article {pmid39451477, year = {2024}, author = {Son, HE and Hong, YS and Lee, S and Son, H}, title = {Prevalence, Risk Factors, and Impact of Long COVID Among Adults in South Korea.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {20}, pages = {}, pmid = {39451477}, issn = {2227-9032}, support = {2022R1F1A106619512//The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; }, abstract = {OBJECTIVES: This study aimed to identify the prevalence, risk factors, and impact of long COVID in a community-based representative sample of patients with COVID-19 aged 19-64 years.

METHODS: A total of 975 participants completed online or telephone surveys at 1 and 3 months post-diagnosis, covering persistent symptoms, daily activity limitations, vaccination status, and underlying diseases.

RESULTS: Long COVID, as defined by the WHO criteria, had a prevalence of 19.7-24.9% in females and 12.7% in males. Logistic regression revealed that the odds of having long COVID symptoms were higher among females compared to males (OR, 2.43; 95% CI, 1.53-3.87), and higher in those aged ≥ 30 years compared to those aged 19-29 years: 30-39 years (OR, 2.91; 95% CI, 1.59-5.33), 40-49 years (OR, 2.72; 95% CI, 1.51-4.89), and 50-64 years (OR, 1.96; 95% CI, 1.10-3.49). Additionally, patients with underlying diseases had higher odds of long COVID symptoms compared to those without underlying diseases (OR, 1.81; 95% CI, 1.24-2.64). Among those with long COVID, 54.2% experienced daily activity limitations, and 40.6% received treatment. Furthermore, lower income groups faced greater daily activity limitations but had similar treatment rates to higher income groups.

CONCLUSIONS: These findings emphasize the need for interest in and the development of programs to support these low-income populations.}, } @article {pmid39450880, year = {2024}, author = {Silver, SR and Li, J and Ford, ND and Saydah, SH}, title = {Functional disabilities and adverse well-being by COVID-19 and Long COVID history and employment status: 2022 Behavioral Risk Factor Surveillance System.}, journal = {American journal of industrial medicine}, volume = {67}, number = {12}, pages = {1089-1107}, pmid = {39450880}, issn = {1097-0274}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Middle Aged ; Adult ; *Behavioral Risk Factor Surveillance System ; Male ; Female ; United States/epidemiology ; *Employment/statistics & numerical data ; Prevalence ; *Disabled Persons/statistics & numerical data ; *SARS-CoV-2 ; Depression/epidemiology ; }, abstract = {BACKGROUND: Long COVID can lead to functional disabilities and decreased well-being and limit the ability to work. No study has yet assessed associations of SARS-CoV-2-infection and Long COVID with specific measures of well-being and functional disabilities among workers by employment status.

METHODS: Using data from the U.S. Behavioral Risk Factor Surveillance System, we assessed the prevalence of functional disabilities and well-being measures among adults of prime working age (25-54 years) by employment status and self-reported COVID-19 and Long COVID history. Within each employment status, we generated adjusted prevalence ratios (aPRs) comparing respondents from each 2022 COVID-19/Long COVID category to respondents in that employment status before the pandemic (2019).

RESULTS: In 2022, prevalences of each functional disability except vision and all adverse well-being measures were highest among the 9.2% of respondents reporting a history of Long COVID. For each outcome, prevalences were lowest for workers and highest among those unable to work. 2022 prevalence of cognitive disability (16.4% of employees, 21.4% of the self-employed) and depression (31.2% and 36.4%, respectively) among workers reporting a history of Long COVID were more than double 2019 levels. Increases in cognitive disability and depression were lower but statistically significant among workers not reporting a history of Long COVID.

CONCLUSIONS: The high prevalence of functional disabilities and adverse well-being among workers reporting a history of Long COVID have implications for workers and employers. Also concerning are smaller increases among workers not reporting a history of Long COVID, given the large number of affected workers. Mitigating the effects of Long COVID on workers will involve efforts in multiple domains: reducing incidence, increasing healthcare practitioner awareness, improving diagnosis and treatments, and increasing employer awareness of best practices for accommodating workers with Long COVID.}, } @article {pmid39450181, year = {2024}, author = {Matula, Z and Király, V and Bekő, G and Gönczi, M and Zóka, A and Steinhauser, R and Uher, F and Vályi-Nagy, I}, title = {High prevalence of long COVID in anti-TPO positive euthyroid individuals with strongly elevated SARS-CoV-2-specific T cell responses and moderately raised anti-spike IgG levels 23 months post-infection.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1448659}, pmid = {39450181}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/epidemiology ; *SARS-CoV-2/immunology ; *Immunoglobulin G/blood/immunology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; *Antibodies, Viral/blood/immunology ; *T-Lymphocytes/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; Autoantibodies/immunology/blood ; Post-Acute COVID-19 Syndrome ; Iodide Peroxidase/immunology ; Prevalence ; Aged ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), causes post-acute infection syndrome in a surprisingly large number of cases worldwide. This condition, also known as long COVID or post-acute sequelae of COVID-19, is characterized by extremely complex symptoms and pathology. There is a growing consensus that this condition is a consequence of virus-induced immune activation and the inflammatory cascade, with its prolonged duration caused by a persistent virus reservoir.

METHODS: In this cross-sectional study, we analyzed the SARS-CoV-2-specific T cell response against the spike, nucleocapsid, and membrane proteins, as well as the levels of spike-specific IgG antibodies in 51 healthcare workers, categorized into long COVID or convalescent control groups based on the presence or absence of post-acute symptoms. Additionally, we compared the levels of autoantibodies previously identified during acute or critical COVID-19, including anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-neutrophil cytoplasmic antibodies, and anti-thyroid peroxidase (anti-TPO). Furthermore, we analyzed the antibody levels targeting six nuclear antigens within the ENA-6 S panel, as positivity for certain anti-nuclear antibodies has recently been shown to associate not only with acute COVID-19 but also with long COVID. Finally, we examined the frequency of diabetes in both groups. Our investigations were conducted at an average of 18.2 months (convalescent control group) and 23.1 months (long COVID group) after confirmed acute COVID-19 infection, and an average of 21 months after booster vaccination.

RESULTS: Our results showed significant differences between the two groups regarding the occurrence of acute infection relative to administering the individual vaccine doses, the frequency of acute symptoms, and the T cell response against all structural SARS-CoV-2 proteins. A statistical association was observed between the incidence of long COVID symptoms and highly elevated anti-TPO antibodies based on Pearson's chi-squared test. Although patients with long COVID showed moderately elevated anti-SARS-CoV-2 spike IgG serum antibody levels compared to control participants, and further differences were found regarding the positivity for anti-nuclear antibodies, anti-dsDNA, and HbA1c levels between the two groups, these differences were not statistically significant.

DISSCUSSION: This study highlights the need for close monitoring of long COVID development in patients with elevated anti-TPO titers, which can be indicated by strongly elevated SARS-CoV-2-specific T cell response and moderately raised anti-spike IgG levels even long after the acute infection. However, our results do not exclude the possibility of new-onset thyroid autoimmunity after COVID-19, and further investigations are required to clarify the etiological link between highly elevated anti-TPO titers and long COVID.}, } @article {pmid39449339, year = {2024}, author = {Qian, CY and Hu, SN and Huadong, L and Liu, JJ}, title = {Potential Mechanisms of Covid-19 Related Nervous System Damage and Effects on Female Fertility.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673333968241011092801}, pmid = {39449339}, issn = {1875-533X}, abstract = {Signs and symptoms that persist or worsen beyond the "acute COVID-19" stage are referred to as long-COVID. These patients are more likely to suffer from multiple organ failure, readmission, and mortality. According to a recent theory, long-lasting COVID-19 symptoms may be caused by abnormal autonomic nervous system (ANS) activity, such as hypovolemia, brain stem involvement, and autoimmune reactions. Furthermore, COVID-19 can also cause impaired fertility in women, which may also be related to inflammation and immune responses. Currently, few treatments are available for long-COVID symptoms. This article reviews the major effects of COVID-19 on the nervous system and female fertility, as well as offers potential treatment approaches.}, } @article {pmid39449018, year = {2024}, author = {Pallan, M and Murphy, M and Morrison, B and Sitch, A and Adamson, A and Bartington, S and Dobell, A and Duff, R and Frew, E and Griffin, T and Hurley, K and Lancashire, E and McLeman, L and Passmore, S and Pokhilenko, I and Rowland, M and Ravaghi, V and Spence, S and Adab, P}, title = {National school food standards in England: a cross-sectional study to explore compliance in secondary schools and impact on pupil nutritional intake.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {21}, number = {1}, pages = {123}, pmid = {39449018}, issn = {1479-5868}, support = {17/92/39//Public Health Research Programme/ ; }, mesh = {Humans ; Cross-Sectional Studies ; England ; *Schools ; Male ; Female ; *Food Services/standards ; *Nutrition Policy ; Adolescent ; Child ; *Students/statistics & numerical data ; Diet/standards ; Nutritive Value ; Guideline Adherence/statistics & numerical data ; Energy Intake ; }, abstract = {BACKGROUND: Many countries have introduced school food standards to improve the dietary intakes of school-aged children. England has school food standards (SFS) legislation in place but little is known about how well secondary schools comply with this. We aimed to assess compliance with the SFS legislation in English secondary schools and explore the impact of the SFS on pupils' nutritional intake.

METHODS: We conducted a cross-sectional study with English secondary schools from 2019 to 2022. We compared SFS compliance and pupil nutritional intake in schools mandated or not mandated to comply with the SFS legislation, and explored the association between school compliance and pupil nutritional intake. We assessed the percentage of SFS (%SFS) complied with by reviewing school food menus and observing food served in school canteens. We assessed pupil nutritional intake using a 24-hour dietary recall measure (Intake24) and estimated intakes of free sugar (primary outcome) and other nutrients/foods. We used adjusted multilevel models to compare pupil intakes in the SFS-mandated and SFS-non-mandated schools, and to explore the association between school SFS compliance and pupil intakes.

RESULTS: 36 schools (23 not mandated and 13 mandated to comply with the SFS) and 2,273 pupils participated. The median %SFS complied with was 63.9% (interquartile range 60.0-70.0%). This was similar for SFS-non-mandated (64.5%) and SFS-mandated schools (63.3%). Compliance was highest for standards applying to lunchtime (median = 81.3%) and lowest for those applying across the whole school day (median = 41.7%). It was also lower for standards restricting high fat, sugar and energy-dense items (median = 26.1%) than for standards aiming to increase dietary variety (median = 92.3%). Pupils from SFS-mandated schools had a lower mean lunchtime intake of free sugar (g) (adjusted mean difference: -2.78g; 95% CI: -4.66g to -0.90g). There were few significant associations between %SFS complied with and pupil nutritional intake.

CONCLUSIONS: English secondary schools do not fully comply with SFS legislation regardless of whether they are mandated to comply. Schools and caterers may require monitoring and support to fully comply. There is little evidence that SFS compliance is associated with better pupil nutritional intake. Food environments outside of school also need to be considered.

STUDY REGISTRATION: ISRCTN68757496 (17-10-2019).}, } @article {pmid39447830, year = {2024}, author = {Nador, E and Mausser, E and Marathe, JG and Politch, JA and Thurman, AR and Whaley, KJ and Anderson, DJ}, title = {Antibody-dependent complement-mediated sperm cytotoxicity in the endocervix is a dominant contraceptive mechanism of ZB-06 vaginal film.}, journal = {Fertility and sterility}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.fertnstert.2024.10.026}, pmid = {39447830}, issn = {1556-5653}, } @article {pmid39446250, year = {2024}, author = {Akase, IE and Agabi, OP and Ojo, OO and Anyanwu, RA and Awodumila, S and Ayilara, S and Ede, OJ and Ghajiga, P and Kalejaiye, O and Nwanmah, C and Nwaokorie, F and Ogbenna, A and Olajide, M and Perez-Giraldo, GS and Orban, ZS and Jimenez, M and Koralnik, IJ and Okubadejo, NU}, title = {A systematic analysis of neurologic manifestations of Long COVID in Nigeria.}, journal = {Journal of neurovirology}, volume = {}, number = {}, pages = {}, pmid = {39446250}, issn = {1538-2443}, support = {Catalyzer award # 1055//Robert J. Havey Institute for Global Health, Northwestern University, Feinberg School of Medicine/ ; }, abstract = {Long COVID, also called post-acute sequelae of SARS-CoV-2 infection (PASC) affects millions of people in the world. The neurologic manifestations of PASC (Neuro-PASC) are among the most debilitating but they are largely unreported in Africa. We sought to compare the demographics, symptoms and cognitive profile of post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients in Nigeria. In this cross-sectional study performed at the Lagos University Teaching Hospital, 106/2319 (4.6%) SARS-CoV-2 positive individuals contacted via telephone reported Neuro-PASC symptoms with a higher frequency in PNP than in NNP individuals ((23/200 (11.5%) vs. 83/2119 (3.9%), p = < 0.0001). The predominant neurologic symptoms at any time during the disease course were difficulty remembering / brain fog (63/106; 59.4%), fatigue (59/106; 55.7%), sleep problems (34/106; 32%), headache (33/106; 31%), paresthesia (12/106; 11.3%), and myalgia (10/106; 9.4%). Of 66 participants with Neuro-PASC who underwent in-person neurological evaluation and cognitive screening, all had normal scores on the Intervention for Dementia in Elderly Africans cognition screen, while 11/65 (16.9%) that completed the Montreal Cognitive Assessment had results consistent with mild cognitive impairment (3/16 PNP (18.8%) and 8/49 NNP (16.3%); p = 1.0). Finally, 47/66 (71.2%) had digit span test scores consistent with mild cognitive dysfunction (12/16 PNP (75%) and 35/50 (70%) NNP; p = 1.0). Our findings reveal the previously unrecognized occurrence of Neuro-PASC among COVID-19 survivors in Nigeria and highlight the need for improved screening and diagnosis of Neuro-PASC in our population. Development of cognitive support services for persons suffering from Neuro-PASC in Nigeria is warranted.}, } @article {pmid39446164, year = {2024}, author = {Ramzi, A and Maya, S and Balousha, N and Amin, M and Shiha, MR}, title = {Pentoxifylline in COVID-19 and considerations for its research in long COVID.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {73}, number = {12}, pages = {2057-2068}, pmid = {39446164}, issn = {1420-908X}, mesh = {*Pentoxifylline/therapeutic use ; Humans ; *COVID-19 Drug Treatment ; *COVID-19 ; SARS-CoV-2/drug effects ; Length of Stay ; }, abstract = {INTRODUCTION: Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research.

METHODS: Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19.

RESULTS: Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration.

CONCLUSION: This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms.}, } @article {pmid39445819, year = {2024}, author = {Eberhardt, J and Gibson, B and Portman, RM and Carthy, N and Rowlands, S and Batchelor, R and Kane, L and Kılınç, S}, title = {Psychosocial Aspects of the Lived Experience of Long COVID: A Systematic Review and Thematic Synthesis of Qualitative Studies.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {5}, pages = {e70071}, pmid = {39445819}, issn = {1369-7625}, support = {//The authors received no specific funding for this work./ ; }, mesh = {Humans ; Adaptation, Psychological ; *Post-Acute COVID-19 Syndrome/psychology/rehabilitation ; Qualitative Research ; SARS-CoV-2 ; *Social Support ; Uncertainty ; }, abstract = {BACKGROUND: Despite increasing recognition of long COVID, the psychosocial impacts of the lived experience on individuals remain underexplored. This systematic review sought to fill this gap by identifying key themes that describe the psychosocial dimensions of long COVID.

OBJECTIVE: The aim of this study is to identify key themes illustrating the psychosocial aspects of individuals' lived experience of long COVID.

SEARCH STRATEGY: Searches were conducted in multiple databases and grey literature sources for qualitative studies published between November 2019 and June 2024.

INCLUSION CRITERIA: Eligible studies involved adult participants self-reporting long COVID. The studies needed to provide qualitative data that could be synthesised thematically.

DATA EXTRACTION AND SYNTHESIS: Data extraction and thematic synthesis were conducted by at least two independent reviewers at each stage. Quality appraisal was performed using the Critical Appraisal Skills Programme tool.

RESULTS: The review included 34 studies. Thematic synthesis yielded five themes: 'Debilitation', 'Uncertainty', 'Sources of Support', 'Meaning Making: Adjusting to a New Normal' and 'Experiences with Healthcare Services'. Individuals with long COVID reported experiencing physical, economic, and social challenges. Uncertainty and scepticism from others caused anxiety. Support from healthcare services, friends and online groups played an important role. Acceptance and gratitude were found to be meaningful in adjusting to the new normal. Experiences with healthcare services varied.

DISCUSSION AND CONCLUSIONS: This review provides valuable insights into the psychosocial impact of long COVID, highlighting the profound changes and challenges that individuals face. Healthcare services should adopt a holistic approach to integrate psychosocial support within their management strategies, to improve overall patient outcomes.}, } @article {pmid39445814, year = {2024}, author = {Grant, A and Stage, E and Blane, D and Goss, H and Ormerod, J and McIver, S and Duncan, E and Patel, G and Campbell, A and Manson, P and Subramanian, G and Cooper, K}, title = {Four Years in, What Are the Research Priorities for Long COVID? A Research Priority-Setting Partnership Between People With Lived Experience, Carers, Clinicians and Researchers.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {5}, pages = {e70072}, pmid = {39445814}, issn = {1369-7625}, support = {//This study was funded by Robert Gordon University./ ; }, mesh = {Humans ; *COVID-19/therapy ; *Caregivers/psychology ; *Health Personnel/psychology ; Research Personnel/psychology ; Post-Acute COVID-19 Syndrome ; Health Priorities ; SARS-CoV-2 ; Research ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Long COVID is a life-limiting condition that affects 65 million people worldwide. It devastates lives with uncertain illness trajectories, and yet, there are many research uncertainties as there is a lack of understanding of its causes, effective treatments and management plans. We set out to identify current research priorities for people with Long COVID, carers, healthcare professionals and researchers.

METHODS: A systematic literature review and previous Long COVID priority-setting exercises identified three broad under-researched areas of Long COVID research within the fields of Public Health and Health Services Research: symptoms; managing day-to-day life; and the emotional impact of Long COVID. We disseminated an elicitation survey that asked for research questions in these areas; responses were analysed and summarised into 42 research questions. A survey was then disseminated, asking respondents to prioritise these 42 questions. Workshops were held with people with Long COVID, carers, healthcare professionals and researchers to analyse responses and agree the top 10 priorities.

RESULTS: The top priorities in order were pharmacological treatment of Long COVID; understanding the pathophysiology; nonpharmacological symptom management; improving public and professional understanding of Long COVID; understanding of the long-term risks of Long COVID; improving financial and social supports; improving understanding of postviral syndromes; diagnostics; service redesign/pathways; and the well-being of children with Long COVID.

CONCLUSION: Four years into the pandemic, there is an emphasis on the need for research on treatment, understanding and support for people living with Long COVID.

People with Long COVID and carers were involved in the study design, survey design, dissemination, data analysis, interpretation and reviewing and editing the manuscript.}, } @article {pmid39444797, year = {2024}, author = {Guo, M and Shang, S and Li, M and Cai, G and Li, P and Chen, X and Li, Q}, title = {Understanding autoimmune response after SARS-CoV-2 infection and the pathogenesis/mechanisms of long COVID.}, journal = {Medical review (2021)}, volume = {4}, number = {5}, pages = {367-383}, pmid = {39444797}, issn = {2749-9642}, abstract = {COVID-19 posed a major challenge to the healthcare system and resources worldwide. The popularization of vaccines and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 pandemic. However, successive occurrence of autoimmune diseases in patients with COVID-19 cannot be overlooked. Long COVID has been the major focus of research due to the long duration of different symptoms and the variety of systems involved. Autoimmunity may play a crucial role in the pathogenesis of long COVID. Here, we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.}, } @article {pmid39444752, year = {2024}, author = {Wang, W and Li, R and Li, C and Liang, Q and Gao, X}, title = {Advances in VNS efficiency and mechanisms of action on cognitive functions.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1452490}, pmid = {39444752}, issn = {1664-042X}, abstract = {OBJECTIVE: This systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer's disease, and other neurological disorders.

METHODS: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords "vagus nerve stimulation," "cognitive enhancement," "emotional processing," "executive function," "learning and memory," "epilepsy," "depression," "Alzheimer's disease," "neurological disorders," "attention-deficit/hyperactivity disorder," "sleep disorders," and "long COVID." The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.

RESULTS: A comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer's disease.

CONCLUSION: VNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.}, } @article {pmid39444602, year = {2024}, author = {He, X and Zhang, X and Zhong, W}, title = {Emerging small-molecule antiviral agents in long COVID prevention.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1457672}, pmid = {39444602}, issn = {1663-9812}, abstract = {Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2 months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention-particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir-may effectively reduce the incidence of long COVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients.}, } @article {pmid39443935, year = {2024}, author = {Gamillscheg, P and Łaszewska, A and Kirchner, S and Hoffmann, K and Simon, J and Mayer, S}, title = {Barriers and facilitators of healthcare access for long COVID-19 patients in a universal healthcare system: qualitative evidence from Austria.}, journal = {International journal for equity in health}, volume = {23}, number = {1}, pages = {220}, pmid = {39443935}, issn = {1475-9276}, support = {SO68900010//Medizinische Universität Wien/ ; SO68900010//Universität Wien/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Austria ; *Health Services Accessibility ; Male ; Female ; *Qualitative Research ; Middle Aged ; Adult ; SARS-CoV-2 ; Focus Groups ; Aged ; Universal Health Care ; Social Stigma ; Healthcare Disparities ; Socioeconomic Factors ; }, abstract = {BACKGROUND: Long COVID-19 challenges health and social systems globally. International research finds major inequalities in prevalence and healthcare utilization as patients describe difficulties with accessing health care. In order to improve long-term outcomes it is vital to understand any underlying access barriers, for which relevant evidence on long COVID-19 is thus far lacking in a universal healthcare system like Austria. This study aims to comprehensively identify access barriers and facilitators faced by long COVID-19 patients in Austria and explore potential socioeconomic and demographic drivers in health and social care access.

METHODS: Applying an exploratory qualitative approach, we conducted semi-structured interviews with 15 experts including medical professionals and senior health officials as well as focus groups with 18 patients with confirmed long COVID-19 diagnosis reflecting varying participant characteristics (age, gender, urbanicity, occupation, education, insurance status) (July-Nov 2023). Data were analysed following a thematic framework approach, drawing on a comprehensive 'access to health care' model.

RESULTS: Based on expert and patient experiences, several access barriers and facilitators emerged along all dimensions of the model. Main themes included scepticism and stigma by medical professionals, difficulties in finding knowledgeable doctors, limited specialist capacities in the ambulatory care sector, long waiting times for specialist care, and limited statutory health insurance coverage of treatments resulting in high out-of-pocket payments. Patients experienced constant self-organization of their patient pathway as stressful, emphasizing the need for multidisciplinary care and centralized coordination. Facilitators included supportive social environments, telemedicine, and informal information provided by a nationwide patient-led support group. Differences in patient experiences emerged, among others, as women and younger patients faced gender- and age-based stigmatization. Complementary health insurance reduced the financial strain, however, did not ease capacity constraints, which were particularly challenging for those living in rural areas.

CONCLUSIONS: The findings of this study indicate a call for action to improve the long COVID-19 situation in Austria by empowering both providers and patients via increased information offerings, strengthened interdisciplinary treatment structures and telemedicine offerings as well as research funding. Our insights on potentially relevant socioeconomic and demographic drivers in access barriers lay the necessary foundation for future quantitative inequality research.}, } @article {pmid39441526, year = {2024}, author = {Quan, SF and Weaver, MD and Czeisler, MÉ and Booker, LA and Jackson, ML and Robbins, R and Howard, ME and Varma, P and Rajaratnam, SMW}, title = {Sleep disturbances are associated with multiple definitions of long COVID.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {}, number = {}, pages = {}, doi = {10.5664/jcsm.11448}, pmid = {39441526}, issn = {1550-9397}, } @article {pmid39438966, year = {2024}, author = {White, RA and Zhang, C and Valcarcel Salamanca, B and Angelsen, A and Zakiudin, DP and Andries, A and Kabashi, S and Moberg, LL}, title = {Aberrations in medically certified sick leave and primary healthcare consultations in Norway in 2023 compared to pre-COVID-19-pandemic trends.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {82}, number = {1}, pages = {187}, pmid = {39438966}, issn = {0778-7367}, abstract = {BACKGROUND: Since 2022, Norway has employed a vaccine-only COVID-19 strategy. Primary healthcare in Norway uses International Classification of Primary Care version 2 (ICPC-2) codes. This study aims to systematically compare medically certified sick leave and primary healthcare consultations in 2023 with the pre-pandemic 2010-2019 trends, and subsequently estimate the magnitude of these changes.

METHODS: For the respective outcomes of (A) working person-years lost to medically certified sick leave (WYLSL) and (B) number of primary healthcare consultations, 556 and 85 ICPC-2 code combinations were extracted from the Norwegian Labour and Welfare Administration's sick leave registry and the Norwegian Syndromic Surveillance System. For each ICPC-2 code combination, a Bayesian linear regression was performed using data between 2010 and 2019 to estimate an expected baseline for 2023, which was then used to calculate the deviation from the pre-pandemic trend. A false discovery rate of 5% was used to account for multiple testing.

RESULTS: All years from 2020 to 2023 had excess WYLSL, corresponding to 14,491 (90% PI: 8,935 to 20,016) in 2020, 12,911 (90% PI: 5,916 to 19,996) in 2021, 21,263 (90% PI: 12,627 to 29,864) in 2022, and 24,466 (90% PI: 14,023 to 34,705) in 2023. This corresponded to an economic loss of approximately 1.5 billion USD in 2023. Excess WYLSL due to A* (General and unspecified) increased from 2020 to 2023, with an estimated excess of 4,136 WYLSL in 2023 (69% higher than expected). More than half of this increase was explained by A04 (Weakness/tiredness general), whose excess WYLSL in 2023 were estimated at 2,640 (80% higher than expected). The excess in A04 (Weakness/tiredness general) corresponded to an economic loss of 161 million USD and accounted for 11% of the total excess WYLSL in 2023. The excess WYLSL in R* (Respiratory) in 2023 was 3,408, which correspond to an economic loss of 207 million USD and accounted for 14% of the total excess in 2023.

CONCLUSIONS: Significant excesses in working person-years lost to medically certified sick leave and primary healthcare consultations in 2023. A sizable proportion of the excesses were due to diseases/symptoms associated with acute and post-acute sequelae of COVID-19.}, } @article {pmid39438926, year = {2024}, author = {Willis, GL and Endo, T and Sakoda, S}, title = {Circadian re-set repairs long-COVID in a prodromal Parkinson's parallel: a case series.}, journal = {Journal of medical case reports}, volume = {18}, number = {1}, pages = {496}, pmid = {39438926}, issn = {1752-1947}, mesh = {Humans ; Male ; Female ; *Parkinson Disease/complications/physiopathology ; *COVID-19/complications/therapy ; Middle Aged ; Aged ; Adult ; Phototherapy/methods ; Prodromal Symptoms ; Sleep Initiation and Maintenance Disorders/etiology ; SARS-CoV-2 ; Circadian Rhythm/physiology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; }, abstract = {BACKGROUND: In this case series, results from daily visual exposure to intense polychromatic light of 2000 to 4000 LUX is presented. Bright light treatment is a standard procedure for treating seasonal affective disorder and prodromal Parkinson's disease with high success. With the post-encephalitic symptoms of long-COVID closely approximating those of prodromal Parkinson's disease, we treated insomnia and sleep-related parameters in these patients, including total sleep, number of awakenings, tendency to fall back to sleep, and fatigue, to determine whether mending sleep could improve quality of life.

CASE PRESENTATION: We present three female and two male Caucasian patients aged 42-70 years with long-COVID that persisted from 12 weeks to 139 weeks after contracting coronavirus disease.

CONCLUSION: A light presentation protocol was adapted for long-COVID that not only restored sleep in all patients, but also unexpectedly repaired the depression, anxiety, and cognitive changes (brain fog) as well. A robust pattern of recovery commencing 4-5 days after treatment and was maintained for weeks to months without relapse. These preliminary findings represent a novel, minimally invasive approach for managing the most debilitating symptoms of long-COVID, making it an ideal candidate for the drug hypersensitive, post-encephalitic brain. That a compromised circadian mechanism seen in Parkinson's disease may also underlie post-encephalitic long-COVID implicates a compromised role of the circadian system in these disorders.}, } @article {pmid39438198, year = {2024}, author = {Warrayat, A and Ali, A and Waked, J and Tocci, D and Speth, RC}, title = {Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2024.10.001}, pmid = {39438198}, issn = {1471-499X}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID. This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients. Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.}, } @article {pmid39438144, year = {2024}, author = {Setiabudi, D and Azhali, BA and Tirtosudiro, MA and Ramadhan, MH and Rinaldhi, M and Nataprawira, HM}, title = {Long COVID or Post-Acute Sequelae of COVID-19 (PASC) in Children and Adolescents.}, journal = {Clinical medicine & research}, volume = {22}, number = {3}, pages = {131-137}, pmid = {39438144}, issn = {1554-6179}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Child ; Adolescent ; Female ; Male ; Cross-Sectional Studies ; Child, Preschool ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Introduction: Few studies of children with long COVID (post-COVID-19 condition) or post-acute sequelae of SARS CoV-2 (PASC) have been reported. Those terms describe symptoms that persist for weeks or months or as new symptoms that develop after SARS-CoV-2 infection. This condition might be found to various degrees in the severity of COVID-19. This study aimed to describe long COVID in confirmed SARS-CoV-2-infected children.Design: An observational cross-sectional study.Setting: Tertiary care hospital between January and November 2021.Participants: Children, age 5-17 years, with virologically confirmed COVID?19.Methods: This study was conducted by completing an electronic form after informed consent was obtained. The subject's characteristics and parent's or guardian's phone numbers were retrieved from the pediatric COVID-19 registry. Parents were contacted to complete a structured electronic questionnaire about the long COVID symptoms noticed in their children. Descriptive statistics were displayed in percentages and median.Results: Parent contact numbers were documented in 125/135 children who fulfilled the study criteria. There were 61 parents (48.8%) who gave consent, while the rest either did not respond or refused. There were 16 children reported as deceased primarily due to chronic renal disease and leukemia. Of the 45 children enrolled, the median (IQR) age was 11 years (5.3-17.6); 51.1% were female; and 75.6% had comorbidities. Two-thirds developed long COVID symptoms, most frequently in the age 5-9 years group, and mostly fatigue (45.2%), decreased appetite (38.7%), and muscle aches (32.3%). All patients with moderate to severe and more than half asymptomatic to mild COVID-19 developed long COVID.Conclusion: Most children had long COVID symptoms similar to adults despite being otherwise asymptomatic or having mild COVID-19.}, } @article {pmid39436613, year = {2024}, author = {Di Fusco, M and Cappelleri, JC and Yehoshua, A and Craig, KJT and Alvarez, MB and Allen, KE and Porter, TM and Lopez, SMC and Puzniak, L and Sun, X}, title = {Associations between symptom-based long COVID clusters and long-term quality of life, work and daily activities among individuals testing positive for SARS-CoV-2 at a national retail pharmacy.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {122}, pmid = {39436613}, issn = {2509-8020}, support = {Not applicable//Pfizer/ ; }, mesh = {Humans ; *Quality of Life ; Male ; Female ; *COVID-19/epidemiology/psychology ; Middle Aged ; Prospective Studies ; Adult ; *SARS-CoV-2 ; *Activities of Daily Living/psychology ; Longitudinal Studies ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; BNT162 Vaccine ; Pharmacies ; Absenteeism ; Efficiency ; }, abstract = {BACKGROUND: Evidence on long COVID symptom clustering patterns among patients with COVID-19 is limited. We summarized long COVID symptoms in clusters defined by number of symptoms co-occurring together, and we assessed Health-Related Quality of Life (HQRoL), Work Productivity and Activity Impairment (WPAI) outcomes across these clusters over time. We assessed associations between the clusters and BNT162b2 vaccination status.

METHODS: A prospective longitudinal patient-reported outcomes (PRO) study recruited laboratory-confirmed symptomatic COVID-19 patients seeking testing from a national retail pharmacy. Long COVID-19 symptoms were self-reported by participants at 4-week, 3-month and 6-month surveys. Patient classes identified via latent class analysis (LCA) with long COVID-19 symptoms were simplified into clusters based on number of symptoms. HRQoL and WPAI outcomes were collected using EQ-ED-5L and WPAI: GH questionnaires. Mixed models for repeated measures analyses were conducted to examine associations between exposure groups and outcomes.

RESULTS: The study included 328 participants that were segmented into three groups of long COVID-19 symptoms based on LCA and then simplified by the number of symptoms (Cluster 1 low, <2; Cluster 2 moderate, 2-6; and Cluster 3 high, >6 symptoms). The number of long COVID-19 symptoms was negatively associated with HRQoL and WPAI, whereby participants with high symptom burden (>6 symptoms) had the lowest HRQoL and WPAI scores assessed by absenteeism, presenteeism, work productivity loss, activity impairment, and hours worked metrics. Compared with those unvaccinated and not up-to-date with COVID-19 vaccination, subjects boosted with BNT162b2 consistently reported less symptom burden during the follow-up, regardless of their symptom-based cluster.

CONCLUSION: Three distinct patient clusters based on frequency of long COVID symptoms experienced different HRQoL and WPAI outcomes over 6 months. The cluster with more concomitant symptoms experienced greater burden than the others. Participants up-to-date with BNT162b2 reported lower symptom burden across all clusters and timeframes.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT05160636.}, } @article {pmid39436440, year = {2024}, author = {Kundi, M}, title = {A short story of long COVID.}, journal = {Wiener klinische Wochenschrift}, volume = {136}, number = {21-22}, pages = {587-589}, pmid = {39436440}, issn = {1613-7671}, } @article {pmid39436395, year = {2024}, author = {Kadl, A and Davis, EM and Oliver, SF and Lazoff, SA and Popovich, J and Atya, AAE and Enfield, KB and Quigg, M}, title = {Prevalence and associations of insomnia after COVID-19 infection.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {}, number = {}, pages = {}, doi = {10.5664/jcsm.11420}, pmid = {39436395}, issn = {1550-9397}, abstract = {STUDY OBJECTIVES: Sleep disturbances in "long COVID" are common, but the associations between the severity of sleep problems and the severity of COVID infection are unclear. We evaluated the prevalence, persistence, comorbidities, and clinical effects of insomnia following recovery from acute COVID-19 infection in a COVID-specific clinic.

METHODS: Inpatients discharged after COVID infection and outpatients referred for persistent post-COVID symptoms were surveyed on insomnia severity (Insomnia Severity Index, ISI), other neuropsychological symptoms, cardiopulmonary symptoms and physiological functions (6 minute walk distance and others), and functional outcome and quality of life (QOL). Multivariable regression models evaluated the severity of ISI against independent variables.

RESULTS: A total of 280 patients met criteria at the initial visit. The prevalence of significant insomnia at the initial visit was 50% and 42% at the subsequent visit (obtained in 78 of the 280 patients). Lower age, female sex, non-white race, and non-Hispanic ethnicity were significantly associated with worse initial ISI scores. More severe symptoms of anxiety and depression were strong correlates with worse ISI scores. Interval improvements in insomnia severity correlated with improvements in anxiety and post-traumatic stress disorder (PTSD) scores. Physiological sequelae of infection did not correlate with insomnia at any stage.

CONCLUSIONS: Initial and persistent insomnia is common in long COVID. Treatment for insomnia with the use of evidence based approaches (such as cognitive behavioral therapy for insomnia) may best suit this particular post-COVID symptom.}, } @article {pmid39435694, year = {2024}, author = {Shekhar Patil, M and Richter, E and Fanning, L and Hendrix, J and Wyns, A and Barrero Santiago, L and Nijs, J and Godderis, L and Polli, A}, title = {Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.}, journal = {Expert reviews in molecular medicine}, volume = {26}, number = {}, pages = {e29}, pmid = {39435694}, issn = {1462-3994}, mesh = {Humans ; *DNA Methylation ; *Epigenesis, Genetic ; MicroRNAs/genetics ; *Post-Acute COVID-19 Syndrome/genetics ; SARS-CoV-2/pathogenicity ; }, abstract = {BACKGROUND: Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic.

METHODS: We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results.

RESULTS: Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID.

CONCLUSION: Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.}, } @article {pmid39435656, year = {2024}, author = {Eaton-Fitch, N and Rudd, P and Er, T and Hool, L and Herrero, L and Marshall-Gradisnik, S}, title = {Immune exhaustion in ME/CFS and long COVID.}, journal = {JCI insight}, volume = {9}, number = {20}, pages = {}, pmid = {39435656}, issn = {2379-3708}, mesh = {Humans ; *COVID-19/immunology ; Male ; Female ; Middle Aged ; *Fatigue Syndrome, Chronic/immunology/virology ; Adult ; *SARS-CoV-2/immunology ; Leukocytes, Mononuclear/immunology/metabolism ; Cytokines/metabolism ; Post-Acute COVID-19 Syndrome ; Aged ; Signal Transduction/immunology ; Case-Control Studies ; Immune System Exhaustion ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are debilitating multisystemic conditions sharing similarities in immune dysregulation and cellular signaling pathways contributing to the pathophysiology. In this study, immune exhaustion gene expression was investigated in participants with ME/CFS or long COVID concurrently. RNA was extracted from peripheral blood mononuclear cells isolated from participants with ME/CFS (n = 14), participants with long COVID (n = 15), and healthy controls (n = 18). Participants with ME/CFS were included according to Canadian Consensus Criteria. Participants with long COVID were eligible according to the case definition for "Post COVID-19 Condition" published by the World Health Organization. RNA was analyzed using the NanoString nCounter Immune Exhaustion gene expression panel. Differential gene expression analysis in ME/CFS revealed downregulated IFN signaling and immunoglobulin genes, and this suggested a state of immune suppression. Pathway analysis implicated dysregulated macrophage activation, cytokine production, and immunodeficiency signaling. Long COVID samples exhibited dysregulated expression of genes regarding antigen presentation, cytokine signaling, and immune activation. Differentially expressed genes were associated with antigen presentation, B cell development, macrophage activation, and cytokine signaling. This investigation elucidates the intricate role of both adaptive and innate immune dysregulation underlying ME/CFS and long COVID, emphasizing the potential importance of immune exhaustion in disease progression.}, } @article {pmid39435149, year = {2024}, author = {Cui, H and Sun, F and Yu, N and Cao, Y and Wang, X and Zhang, D and Chen, Z and Wang, N and Yuan, B and Liu, P and Duan, W and Qiu, W and Yin, X and Ma, C}, title = {TLR2/NF-κB signaling in macrophage/microglia mediated COVID-pain induced by SARS-CoV-2 envelope protein.}, journal = {iScience}, volume = {27}, number = {10}, pages = {111027}, pmid = {39435149}, issn = {2589-0042}, abstract = {Pain has become a major symptom of long COVID-19 without effective therapy. Apart from viral infection pathological process, SARS-CoV-2 membranal proteins (envelope [S2E], spike [S2S] and membrane [S2M]) also present pro-inflammatory feature independently. Here, we aim to uncover the neuroinflammatory mechanism of COVID-pain induced by SARS-CoV-2 membranal proteins. We detected the three proteins in both peripheral sensory ganglions and spinal dorsal horn of COVID-19 donors. After intradermal and intrathecal injection, only S2E triggered pain behaviors, accompanied with upregulated-phosphorylation nuclear factor kappa B (NF-κB), which was significantly attenuated by minocycline in mice. We further identified Toll-like receptor 2 (TLR2) among TLRs as the target of S2E to evoke inflammatory responses leading to COVID-pain. This study identified the nociceptive effect of S2E through directly interacting with macrophage/microglia TLR2 and inducing the following NF-κB inflammatory storm. Clearing away S2E and inhibiting macrophage/microglia TLR2 served as perspective therapeutic strategies for COVID-19 pain.}, } @article {pmid39434957, year = {2024}, author = {Kell, DB and Khan, MA and Pretorius, E}, title = {Fibrinaloid microclots in long COVID: assessing the actual evidence properly.}, journal = {Research and practice in thrombosis and haemostasis}, volume = {8}, number = {7}, pages = {102566}, pmid = {39434957}, issn = {2475-0379}, } @article {pmid39434919, year = {2024}, author = {Blanchard, M and Venerito, V and Ming Azevedo, P and Hügle, T}, title = {Generative AI-based knowledge graphs for the illustration and development of mHealth self-management content.}, journal = {Frontiers in digital health}, volume = {6}, number = {}, pages = {1466211}, pmid = {39434919}, issn = {2673-253X}, abstract = {BACKGROUND: Digital therapeutics (DTx) in the form of mobile health (mHealth) self-management programs have demonstrated effectiveness in reducing disease activity across various diseases, including fibromyalgia and arthritis. However, the content of online self-management programs varies widely, making them difficult to compare.

AIM: This study aims to employ generative artificial intelligence (AI)-based knowledge graphs and network analysis to categorize and structure mHealth content at the example of a fibromyalgia self-management program.

METHODS: A multimodal mHealth online self-management program targeting fibromyalgia and post-viral fibromyalgia-like syndromes was developed. In addition to general content, the program was customized to address specific features and digital personas identified through hierarchical agglomerative clustering applied to a cohort of 202 patients with chronic musculoskeletal pain syndromes undergoing multimodal assessment. Text files consisting of 22,150 words divided into 24 modules were used as the input data. Two generative AI web applications, ChatGPT-4 (OpenAI) and Infranodus (Nodus Labs), were used to create knowledge graphs and perform text network analysis, including 3D visualization. A sentiment analysis of 129 patient feedback entries was performed.

RESULTS: The ChatGPT-generated knowledge graph model provided a simple visual overview with five primary edges: "Mental health challenges", "Stress and its impact", "Immune system function", "Long COVID and fibromyalgia" and "Pain management and therapeutic approaches". The 3D visualization provided a more complex knowledge graph, with the term "pain" appearing as the central edge, closely connecting with "sleep", "body", and "stress". Topical cluster analysis identified categories such as "chronic pain management", "sleep hygiene", "immune system function", "cognitive therapy", "healthy eating", "emotional development", "fibromyalgia causes", and "deep relaxation". Gap analysis highlighted missing links, such as between "negative behavior" and "systemic inflammation". Retro-engineering of the self-management program showed significant conceptual similarities between the knowledge graph and the original text analysis. Sentiment analysis of free text patient comments revealed that most relevant topics were addressed by the online program, with the exception of social contacts.

CONCLUSION: Generative AI tools for text network analysis can effectively structure and illustrate DTx content. Knowledge graphs are valuable for increasing the transparency of self-management programs, developing new conceptual frameworks, and incorporating feedback loops.}, } @article {pmid39434281, year = {2024}, author = {Al-Rubaey, MG and Salman, AA}, title = {Factors affecting symptom duration and recovery among home-treated COVID- 19 patients in Baghdad-Iraq: a cross-sectional study.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {74}, number = {10 (Supple-8)}, pages = {S95-S99}, doi = {10.47391/JPMA-BAGH-16-22}, pmid = {39434281}, issn = {0030-9982}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Male ; Female ; Adult ; Middle Aged ; Cross-Sectional Studies ; Iraq/epidemiology ; Aged ; *SARS-CoV-2 ; Adolescent ; Young Adult ; Time Factors ; Comorbidity ; Prevalence ; Fatigue/epidemiology ; }, abstract = {OBJECTIVE: To determine the prevalence of Long COVID among home-treated coronavirus disease-2019 cases, and the factors that may influence the duration of symptoms.

METHODS: The cross-sectional study was conducted from February to July 2021 at 20 primary healthcare centres in 10 health districts of Baghdad, Iraq, after approval from the ethics review committee of the College of Medicine, Mustansiriyah University, Baghdad. Those included were adults of both genders who previously had coronavirus disease-2019 infection as diagnosed through on polymerase chain reaction test, and received supportive treatment during isolation at home. Data was collected through direct interview using a questionnaire which consisted of demographic characteristics, comorbidities, smoking history and symptoms of coronavirus disease-2019 along with their duration. Measurement of weight and height was also done for each subject. Data was analysed using SPSS 27.

RESULTS: Of the 400 participants, 248(62%) were males and 152(38%) were females. The overall mean age was 40.8±12.8 years (range: 18-71 years). Of the total, 121(30.25%) subjects had persistent symptoms for >4 weeks. The mean duration of illness was 4.2±3.6 weeks (range: 1-16 weeks). The symptoms that lasted for >4 weeks were fatigue 94(23.5%), loss of smell or taste 59(14.75%), and cough 8(2%). Age, smoking status, comorbidities and the total number of initial symptoms showed a significant association with the duration of illness (p<0.05).

CONCLUSIONS: A substantial number of mild to moderate coronavirus disease-2019 cases suffered from persistent symptoms. The duration of illness could have been influenced by age, comorbidities, smoking status and total number of initial symptoms.}, } @article {pmid39434179, year = {2024}, author = {Vanova, M and Patel, AMR and Scott, I and Gilpin, G and Manning, EN and Ash, C and Wittenberg, P and Lim, J and Hoare, Z and Evans, R and Bray, N and Kipps, CM and Devine, C and Ahmed, S and Dunne, R and Koniotes, A and Warren, C and Chan, D and Suarez-Gonzalez, A}, title = {Telehealth-delivered cognitive rehabilitation for people with cognitive impairment as part of the post-COVID syndrome: protocol for a randomised controlled trial as part of the CICERO (Cognitive Impairment in Long COVID: Phenotyping and Rehabilitation) study.}, journal = {Trials}, volume = {25}, number = {1}, pages = {704}, pmid = {39434179}, issn = {1745-6215}, mesh = {Humans ; *COVID-19/rehabilitation/psychology ; *Cognitive Dysfunction/rehabilitation/psychology/diagnosis ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Randomized Controlled Trials as Topic ; Adult ; SARS-CoV-2 ; Quality of Life ; Multicenter Studies as Topic ; Female ; Male ; Telemedicine ; Treatment Outcome ; Cognition ; Telerehabilitation ; England ; Cognitive Behavioral Therapy/methods ; Cognitive Training ; }, abstract = {BACKGROUND: Between 25 and 75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. Despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care.

METHODS: This is a multi-centre, parallel-group, individually randomised controlled trial, comparing standard clinical care with and without cognitive rehabilitation. We will recruit 120 non-hospitalised adults (aged 30-60 years) from three NHS sites in England with a history of COVID-19 infection and cognitive impairment persisting more than 3 months after the acute infection. Participants will be randomised (1:1) to the intervention or control groups, with the latter represented as a provision of standard clinical care without cognitive rehabilitation. The cognitive rehabilitation programme consists of ten 1-hour sessions, delivered weekly. Outcomes will be collected at baseline, 3, and 6 months, with participant-defined goal-attainment scores, relating to functional goals, at 3 months as the primary outcome measure. Secondary outcomes will be cognitive function, measures of quality of life, social functioning, mental health, fatigue, sleep, post-exertional malaise, and social and health care service use. We will also evaluate the health-economic benefits of cognitive rehabilitation in this population.

DISCUSSION: Cognitive impairment in PASC is a major cause of functional disability with no effective treatment. Accordingly, we will undertake an RCT of cognitive rehabilitation, the protocol of which is published here. If this trial is successful in delivering improvements in trial outcomes, it will address a major unmet need relating to this emergent disorder, with a significant impact on affected individuals and the wider health economy.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05731570. Registered on February 16, 2023.}, } @article {pmid39433997, year = {2024}, author = {Moreels, S and Bensemmane, S and De Schreye, R and Cuschieri, S}, title = {Caring for Long Covid patients in primary healthcare: a cross-sectional study on general practitioners' knowledge, perception and experience in Belgium and Malta.}, journal = {BMC primary care}, volume = {25}, number = {1}, pages = {375}, pmid = {39433997}, issn = {2731-4553}, mesh = {Humans ; Belgium/epidemiology ; *COVID-19/epidemiology/psychology ; Malta/epidemiology ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; *General Practitioners ; Adult ; *Primary Health Care ; *Health Knowledge, Attitudes, Practice ; SARS-CoV-2 ; Surveys and Questionnaires ; Practice Patterns, Physicians' ; Attitude of Health Personnel ; Clinical Competence ; }, abstract = {BACKGROUND: At least 10% of Covid-19 recovered individuals experience persistent symptoms (Long Covid). Primary healthcare and general practitioners (GPs) are at the forefront in their care. In this study, GPs' knowledge, perceptions and experiences with Long Covid, and the definition used in two countries, are investigated to provide insight into GPs' care for Long Covid patients at a cross-country level.

METHODS: A cross-sectional study targeted towards GPs was conducted in Belgium and Malta during spring and early summer 2022. An online survey consisting of 15 questions on Long Covid was disseminated. Additionally, country-specific practice and demographic characteristics were collected. Descriptive and logistic regression analyses were performed.

RESULTS: A total of 150 GPs (Belgium = 105; Malta = 45) responded. Female GPs represented 58.0%, median age was 49 years (IQR: 37-61). Concerning GPs' knowledge and perception on Long Covid, in both countries, most GPs reported insufficient scientific knowledge and information on Long Covid diagnosis and treatment. Access to educational material was limited and an awareness-rising campaign on Long Covid was deemed necessary. Moreover, two out of three GPs stated that Long Covid patients were not well followed up by primary healthcare in mid-2022. For diagnosing Long Covid, 54.7% required a positive Covid-19 test, more often among Belgian GPs than Maltese (64.3% vs. 45.2%, p = 0.036). To assess Long Covid, GPs mainly applied diagnostic criteria by themselves (47.3%) in combination with persistent symptoms (4 weeks to 5 months). Most GPs had experience with Long Covid patients in their practice, regardless of practice type and GPs' country, sex or age (p = 0.353; p = 0.241; p = 0.194; p = 0.058). Although most GPs (94.7%) stated that Long Covid patients should follow multidisciplinary approach, 48.3% reported providing care for these patients themselves or with GP colleagues and only 29.8% by multidisciplinary cooperation.

CONCLUSIONS: GPs frequently provide (multidisciplinary) care to Long Covid patients and GPs' care showed similarities at cross-country level. Although GPs perceive lack of scientific knowledge and educational material on Long Covid, similar diagnostic criteria among GPs were noted. Uniform evidence-based guidelines, scientific support and training for GP across Europe must be a priority to enhance their treatment approach to Long Covid.}, } @article {pmid39433942, year = {2024}, author = {O'Neil, ST and Madlock-Brown, C and Wilkins, KJ and McGrath, BM and Davis, HE and Assaf, GS and Wei, H and Zareie, P and French, ET and Loomba, J and McMurry, JA and Zhou, A and Chute, CG and Moffitt, RA and Pfaff, ER and Yoo, YJ and Leese, P and Chew, RF and Lieberman, M and Haendel, MA and , }, title = {Finding Long-COVID: temporal topic modeling of electronic health records from the N3C and RECOVER programs.}, journal = {NPJ digital medicine}, volume = {7}, number = {1}, pages = {296}, pmid = {39433942}, issn = {2398-6352}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UM1 TR004360/TR/NCATS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; TR002306//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; OT2HL161847-01//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.}, } @article {pmid39433402, year = {2024}, author = {Pazukhina, E and Garcia-Gallo, E and Reyes, LF and Kildal, AB and Jassat, W and Dryden, M and Holter, JC and Chatterjee, A and Gomez, K and Søraas, A and Puntoni, M and Latronico, N and Bozza, FA and Edelstein, M and Gonçalves, BP and Kartsonaki, C and Kruglova, O and Gaião, S and Chow, YP and Doshi, Y and Duque Vallejo, SI and Ibáñez-Prada, ED and Fuentes, YV and Hastie, C and O'Hara, ME and Balan, V and Menkir, T and Merson, L and Kelly, S and Citarella, BW and Semple, MG and Scott, JT and Munblit, D and Sigfrid, L and , }, title = {Long Covid: a global health issue - a prospective, cohort study set in four continents.}, journal = {BMJ global health}, volume = {9}, number = {10}, pages = {}, pmid = {39433402}, issn = {2059-7908}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Prospective Studies ; Middle Aged ; Adult ; *Global Health ; *SARS-CoV-2 ; *Developing Countries ; *Post-Acute COVID-19 Syndrome ; Europe/epidemiology ; Prevalence ; Asia/epidemiology ; Developed Countries ; Africa/epidemiology ; South America/epidemiology ; Cohort Studies ; }, abstract = {INTRODUCTION: A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).

METHODS: A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium's Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.

RESULTS: Of 11 860 participants (median age: 52 (IQR: 41-62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.

CONCLUSION: Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.}, } @article {pmid39430651, year = {2024}, author = {McGill, SC}, title = {Preprint pointers from a long COVID scoping review: considerations for source selection and searching.}, journal = {The journal of the Canadian Health Libraries Association}, volume = {45}, number = {2}, pages = {88-97}, pmid = {39430651}, issn = {1708-6892}, abstract = {This paper describes the search approach for preprints for a post COVID-19 condition (i.e., long COVID) scoping review, including source selection, search strategy development, challenges, and insights throughout a project life cycle. With the growth of medical preprints since the COVID-19 pandemic, information professionals and researchers should be aware that preprints are possible sources of evidence and be prepared to manage them in evidence reviews for COVID-19 topics and beyond. Preprints are not peer-reviewed but can include important evidence about emerging topics. Because of the importance of preprints to the scoping review, a preprint search of Europe PubMed Central (PMC) was added. Europe PMC and similar aggregators combine multiple preprint servers and often have Boolean search, but sometimes limited search functionalities or few export options. Strategy translation encountered challenges such as varying and inconsistent terminology for post-COVID-19 condition, a complex search, and negotiating large numbers of preprints with resource constraints. Europe PMC identified additional preprints for inclusion due to additional preprint server coverage. It was helpful to limit the preprint search to the title and abstract fields, and to run an extra Internet search for publication of included study preprints. Challenges and potential solutions are summarized to support those conducting preprint searches for COVID-19 and other topics.}, } @article {pmid39430594, year = {2024}, author = {Aldhawyan, AF and BuSaad, MA and Almaghlouth, NE and Alnasser, AH and Alnasser, JA and Almansour, AH and AlHarkan, KS}, title = {Understanding long COVID: prevalence, characteristics, and risk factors in the Eastern Province of Saudi Arabia.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1459583}, pmid = {39430594}, issn = {2296-858X}, abstract = {BACKGROUND: The COVID-19 pandemic has significantly raised public health concerns and efforts to limit its spread, impacting societies and health systems worldwide. As challenges persist, the emergence of Long COVID (LC) marks a turning point in understanding the pandemic's long-term effects.

AIM: This study aimed to determine the prevalence of LC in the Eastern Province of the Kingdom of Saudi Arabia (KSA) and explore factors contributing to its persistence.

METHODS: This descriptive, cross-sectional, questionnaire-based study was carried out between December 1, 2023, and March 1, 2024, involving 1,355 patients who recovered from COVID-19. Participants were conveniently chosen and information was gathered through in-person interviews in public settings after obtaining consent.

RESULTS: A majority of the patients (N = 1,355; 47.5% female; 93.8% Saudis; mean Age ± SD 33.13 ± 12.60 years) had received three COVID-19 vaccine doses (89.5%). Women experienced 17.4% more LC symptoms than men (p < 0.001). The risk of having a higher symptom count increased by 42.5% 12 months after acute COVID-19 infection compared with baseline (<3 months, p < 0.001). A higher body mass index (BMI) was associated with more symptoms (1.1% increase per unit, p = 0.004). More acute-phase symptoms correlated with more LC symptoms (p < 0.001). Higher educational attainment reduced LC risk by 33% (p < 0.001). Finally, age and vaccination status had no effect on LC symptoms count (p > 0.05).

CONCLUSION: Sociodemographic and clinical factors contribute differently to the chances of having LC and the count of symptoms. Awareness of such factors could provide insight into improving management, leading to better health outcomes.}, } @article {pmid39429966, year = {2024}, author = {Prosperini, L and Arrambide, G and Celius, EG and Goletti, D and Killestein, J and Kos, D and Lavorgna, L and Louapre, C and Sormani, MP and Stastna, D and Ziemssen, T and Di Filippo, M}, title = {COVID-19 and multiple sclerosis: challenges and lessons for patient care.}, journal = {The Lancet regional health. Europe}, volume = {44}, number = {}, pages = {100979}, pmid = {39429966}, issn = {2666-7762}, abstract = {During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trigger the initial demyelinating event or exacerbate disease activity. Another major concern was the safety and efficacy of the COVID-19 vaccines, especially for patients undergoing specific treatments that could weaken their antibody responses. In the post-infection phase, identifying long COVID in patients with MS has been complicated due to the large overlap between post-infection sequelae and MS symptoms. In addition, disruptions in health and rehabilitation services have made it difficult for MS patients to access care. This Series article explores current evidence on the interaction between MS and SARS-CoV-2, identifies the challenges posed by the COVID-19 pandemic in the care of patients with MS, and discusses the significant adoption of digital health solutions, including telemedicine and new technology-based rehabilitation approaches. Based on lessons learned, recommendations and future directions are offered for managing patients with MS, rethinking healthcare systems and improving health outcomes in the post-COVID-19 pandemic era.}, } @article {pmid39429741, year = {2024}, author = {Zhang, S and Wu, Y and Mprah, R and Wang, M}, title = {COVID-19 and persistent symptoms: implications for polycystic ovary syndrome and its management.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1434331}, pmid = {39429741}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/therapy/complications ; *COVID-19/complications/therapy/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has left a profound mark on global health, leading to substantial morbidity and mortality worldwide. Beyond the immediate symptoms of infection, the emergence of "long COVID", the long-term effects of SARS-CoV-2, has become a significant public health concern. Long COVID is a multifaceted condition affecting various organs and systems, including the cardiovascular, digestive, nervous, and endocrine systems. Individuals diagnosed with polycystic ovary syndrome (PCOS) may face an increased risk of severe COVID-19 symptoms and infection. It is crucial to comprehend how long COVID affects PCOS patients to devise effective treatment and care strategies. Here, we review the detrimental effects of COVID-19 and its long-term effects on reproductive health, endocrine function, inflammation, metabolism, cardiovascular health, body composition, lifestyle, and mental health in patients with PCOS. We offer recommendations for the post-covid-19 management of PCOS, emphasizing the necessity of a comprehensive, multidisciplinary approach to patient care. Furthermore, we discuss prospective research directions, highlighting the significance of continued investigations and clinical trials to evaluate treatment approaches for long COVID and its ramifications in individuals with PCOS.}, } @article {pmid39429336, year = {2024}, author = {Bohac, M and Chotárová, M and Mitevová, D and Mayer, A}, title = {COVID-19 Infection and Vaccination Effects on Breast Implant Illness: A Case Report.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69772}, pmid = {39429336}, issn = {2168-8184}, abstract = {Breast implant illness (BII) is a term used to describe a range of symptoms associated with silicone breast implants. This condition suggests that silicone may trigger symptoms in individuals who are immunologically predisposed, and the spectrum of symptoms may be linked to autonomic dysregulation in these patients. We present the case of a female patient in her mid-40s with a history of autoimmune thyroiditis who had not required prior therapy. She underwent breast augmentation and subsequently developed gradual difficulties. After recovering from a COVID-19 infection, her nonspecific symptoms, consistent with BII, worsened. These symptoms included chronic fatigue, hair loss, dry skin, petechiae, low-grade fever, and frequent urination. Additionally, she developed symptoms associated with long COVID. A subsequent Pfizer-BioNTech COVID-19 vaccination further exacerbated her symptoms and overall condition. Due to the broad spectrum of nonspecific symptoms, the patient underwent numerous screenings over an 18-month period, which were inconclusive. We hypothesize that the vaccination and previous infection had a synergistic effect on her ongoing BII symptoms, contributing to the worsening of her condition. An isolated right-sided seroma with left-sided lymphadenopathy appeared to be a side effect of the vaccine. Additionally, the patient developed a newly diagnosed allergy to polyethylene glycol and other allergic manifestations, such as chronic urticaria, which are consistent with autonomic nervous system dysregulation and long COVID. These symptoms resolved within three weeks of explantation with en bloc capsulectomy. It is noteworthy that the patient was unaware of BII until an MRI revealed a suspected intracapsular implant rupture on the right side, which led to the decision to remove the implants.}, } @article {pmid39429158, year = {2024}, author = {Elneima, O and McAuley, HJC and Leavy, OC and Chalmers, JD and Horsley, A and Ho, LP and Marks, M and Poinasamy, K and Raman, B and Shikotra, A and Singapuri, A and Sereno, M and Harris, VC and Houchen-Wolloff, L and Saunders, RM and Greening, NJ and Richardson, M and Quint, JK and Briggs, A and Docherty, AB and Kerr, S and Harrison, EM and Lone, NI and Thorpe, M and Heaney, LG and Lewis, KE and Aul, R and Beirne, P and Bolton, CE and Brown, JS and Choudhury, G and Bakerly, ND and Easom, N and Echevarria, C and Fuld, J and Hart, N and Hurst, JR and Jones, MG and Parekh, D and Pfeffer, P and Rahman, NM and Rowland-Jones, SL and Thompson, AR and Jolley, C and Shah, AM and Wootton, DG and Chalder, T and Davies, MJ and De Soyza, A and Geddes, JR and Greenhalf, W and Heller, S and Howard, LS and Jacob, J and Jenkins, RG and Lord, JM and Man, WD and McCann, GP and Neubauer, S and Openshaw, PJ and Porter, JC and Rowland, MJ and Scott, JT and Semple, MG and Singh, SJ and Thomas, DC and Toshner, M and Smith, N and Sheikh, A and Brightling, CE and Wain, LV and Evans, RA and , }, title = {Cohort Profile: Post-Hospitalisation COVID-19 (PHOSP-COVID) study.}, journal = {International journal of epidemiology}, volume = {53}, number = {1}, pages = {}, pmid = {39429158}, issn = {1464-3685}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1//National Institute of Health Research/ ; 209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; //UK Research and Innovation/ ; }, } @article {pmid39428555, year = {2024}, author = {Park, ES and Shin, CY and Jeon, SJ and Ham, BJ}, title = {Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.}, journal = {Biomolecules & therapeutics}, volume = {32}, number = {6}, pages = {659-684}, pmid = {39428555}, issn = {1976-9148}, abstract = {Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.}, } @article {pmid39426876, year = {2024}, author = {Gaudry, C and Dhersin, R and Dubée, V}, title = {[Mechanisms of prolonged symptoms following acute COVID-19: Some pathophysiological pathways].}, journal = {Revue des maladies respiratoires}, volume = {41}, number = {9}, pages = {660-668}, doi = {10.1016/j.rmr.2024.07.009}, pmid = {39426876}, issn = {1776-2588}, mesh = {Humans ; Dyspnea/epidemiology/immunology/physiopathology/virology ; Fatigue/epidemiology/immunology/physiopathology/virology ; France/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/physiopathology/virology ; *SARS-CoV-2/immunology ; }, abstract = {INTRODUCTION: Following the Omicron wave in early 2022, an estimated 60-70% of the French population was infected with the SARS-CoV-2 virus. One out of ten infected subjects could have persistent symptoms three months after infection, representing a public health challenge.

CURRENT STATE OF KNOWLEDGE: The persistent symptoms may be secondary to diverse entities with distinct mechanisms. While organic infection sequelae occur mainly after severe COVID-19, some symptoms appear to be essentially psychological in origin; in addition, many subjects present stereotyped symptoms of fluctuating intensity with no identified anatomical or psychic substratum, often in the aftermath of a benign infection. The most frequent complaints are fatigue, pain, dyspnea and difficulty concentrating.

PERSPECTIVES: The hypotheses explored to explain these symptoms include: persistent immune dysfunction, inducted autoimmunity, and microbiome disturbances. Persistent viral antigens may lie at the crossroads of these mechanisms. To date, these different etiological avenues have yet to lead to the development of diagnostic tests or specific therapeutic strategies.

CONCLUSION: Prolonged symptoms after COVID-19 correspond to heterogeneous nosological entities with poorly understood mechanisms.}, } @article {pmid39426837, year = {2024}, author = {Payne, AB and Watts, JA and Mitchell, PK and Dascomb, K and Irving, SA and Klein, NP and Grannis, SJ and Ong, TC and Ball, SW and DeSilva, MB and Natarajan, K and Sheffield, T and Bride, D and Arndorfer, J and Naleway, AL and Koppolu, P and Fireman, B and Zerbo, O and Timbol, J and Goddard, K and Dixon, BE and Fadel, WF and Rogerson, C and Allen, KS and Rao, S and Mayer, D and Barron, M and Reese, SE and Rowley, EAK and Najdowski, M and Ciesla, AA and Mak, J and Reeves, EL and Akinsete, OO and McEvoy, CE and Essien, IJ and Tenforde, MW and Fleming-Dutra, KE and Link-Gelles, R}, title = {Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis.}, journal = {Lancet (London, England)}, volume = {404}, number = {10462}, pages = {1547-1559}, doi = {10.1016/S0140-6736(24)01738-0}, pmid = {39426837}, issn = {1474-547X}, mesh = {Humans ; *Respiratory Syncytial Virus Infections/prevention & control/epidemiology ; *Hospitalization/statistics & numerical data ; *Respiratory Syncytial Virus Vaccines/immunology ; Male ; Middle Aged ; Female ; United States/epidemiology ; *Emergency Service, Hospital/statistics & numerical data ; Aged ; *Vaccine Efficacy ; Respiratory Syncytial Virus, Human/immunology ; Aged, 80 and over ; }, abstract = {BACKGROUND: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years.

METHODS: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region.

FINDINGS: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type.

INTERPRETATION: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved.

FUNDING: The Centers for Disease Control and Prevention.}, } @article {pmid39425101, year = {2024}, author = {Moniz, M and Ruivinho, C and Goes, AR and Soares, P and Leite, A}, title = {Correction: Long COVID is not the same for everyone: a hierarchical cluster analysis of long COVID symptoms 9 and 12 months after SARS-CoV-2 test.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1178}, pmid = {39425101}, issn = {1471-2334}, } @article {pmid39425012, year = {2024}, author = {Dwiputra, B and Ambari, AM and Triangto, K and Supriami, K and Kesuma, TW and Zuhdi, N and Phowira, J and Radi, B}, title = {The home-based breathing and chest mobility exercise improves cardiorespiratory functional capacity in long COVID with cardiovascular comorbidities: a randomized study.}, journal = {BMC cardiovascular disorders}, volume = {24}, number = {1}, pages = {574}, pmid = {39425012}, issn = {1471-2261}, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Middle Aged ; Single-Blind Method ; Aged ; *Breathing Exercises/methods ; *Cardiac Rehabilitation/methods ; *Cardiovascular Diseases/physiopathology/diagnosis ; *Cardiorespiratory Fitness ; Exercise Tolerance ; Quality of Life ; Exercise Therapy/methods ; Treatment Outcome ; Home Care Services ; Comorbidity ; Time Factors ; Recovery of Function ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Beyond the acute phase, a considerable proportion of patients recovering from the coronavirus disease 2019 (COVID-19) experience long-term sequelae that profoundly impact their quality of life, particularly their physical fitness. This study aims to assess the effect of home-based breathing and chest mobility exercise on the cardiorespiratory functional capacity of long COVID with cardiovascular comorbidity.

METHODS: In this randomized, controlled, single-blind clinical trial, 46 long COVID with cardiovascular comorbidities were randomly assigned to either intervention or control group. The intervention group (n = 23) received additional home-based breathing and chest mobility exercise 3x/week for 12 weeks supervised by attending physicians, whereas the control group only received a home-based cardiac rehabilitation program. Baseline and post-intervention assessments consisted of laboratory (D-Dimer and CRP levels) and functional capacity, assessed through 6-minute walking test (6-MWT), exercise stress test's metabolic equivalents (METS), and predicted peak oxygen consumption (VO2 peak), peak expiratory flow rate (PEFR), peak cough flow (PCF), chest expansion, and EuroQoL's quality of life. Intention to treat analysis was performed.

RESULTS: At the 12th week, intervention subjects had significantly greater functional capacity with higher mean PEFR (p = .031) and PCF (p = .016). Similarly, 6-MWT was higher in the group receiving home-based breathing and chest mobility training (p = .032). The bottom part of the chest circumference was statistically different between the two groups (p = .01). METS and predicted VO2 peak were also higher in the intervention group. However, laboratory parameters and quality of life did not differ markedly (p > .05).

CONCLUSIONS: Home-based respiratory and chest mobility exercise could be an adjunct to cardiac rehabilitation in long COVID with cardiovascular comorbidities for improving cardiorespiratory functional capacity.

TRIAL REGISTRATION: The study protocol was registered at http://ClinicalTrial.gov.id NCT05077943 (14/10/2021).}, } @article {pmid39424264, year = {2024}, author = {Almulla, AF and Thipakorn, Y and Zhou, B and Vojdani, A and Paunova, R and Maes, M}, title = {The tryptophan catabolite or kynurenine pathway in long COVID disease: A systematic review and meta-analysis.}, journal = {Neuroscience}, volume = {563}, number = {}, pages = {268-277}, doi = {10.1016/j.neuroscience.2024.10.021}, pmid = {39424264}, issn = {1873-7544}, mesh = {Humans ; *Kynurenine/metabolism/analogs & derivatives ; *Tryptophan/metabolism ; *COVID-19/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Recent studies confirm the involvement of activated immune-inflammatory responses and increased oxidative and nitrosative stress in Long COVID (LC) disease. However, the influence of these pathways on the metabolism of tryptophan (TRP) through the TRP catabolite (TRYCAT) pathway and their mediating effects on LC pathophysiology, has not been fully explored.

OBJECTIVE: This meta-analysis investigates peripheral TRP and TRYCAT levels and the TRYCAT pathway in patients with LC disease.

METHOD: This review utilized systematic searches of PubMed, Google Scholar, SCOPUS and SciFinder, including 14 full-text articles and 1,167 participants, consisting of 480 patients with LC and 687 normal controls.

RESULTS: The results indicated a significant increase in the kynurenine (KYN)/TRP ratio, with a large effect size (standardized mean difference, SMD = 0.755; confidence intervals, CI: 0.119;1.392), in LC patients compared to normal controls. Additionally, LC patients exhibited a significant decrease in TRP levels (SMD = -0.520, CI: -0.793; -0.246) and an increase in KYN levels after imputing missing studies (SMD = 1.176, CI: 0.474; 1.877), suggesting activation of the indoleamine 2,3-dioxygenase (IDO) enzyme and upregulation of the TRYCAT pathway. No significant elevation in TRYCAT-related neurotoxicity, kynurenic acid (KA)/KYN and 3-hydroxykynurenine (3-HK)/KYN ratios were observed in LC patients compared to normal controls.

CONCLUSION: The current findings suggest that an activated TRYCAT pathway, characterized by decreased TRP levels and maybe elevated KYN levels, plays a significant role in the pathophysiology of LC.}, } @article {pmid39423876, year = {2024}, author = {Meirman, TD and Shapira, B and Balicer, RD and Rokach, L and Dagan, N}, title = {Trends of common laboratory biomarkers after SARS-CoV-2 infection.}, journal = {The Journal of infection}, volume = {89}, number = {6}, pages = {106318}, doi = {10.1016/j.jinf.2024.106318}, pmid = {39423876}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/blood/diagnosis ; *Biomarkers/blood ; Male ; Female ; Middle Aged ; Retrospective Studies ; *SARS-CoV-2 ; Adult ; Aged ; Leukocyte Count ; Young Adult ; }, abstract = {BACKGROUND: Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers.

METHODS: We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences.

RESULTS: The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1-4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7-8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3-5 months. Vaccinated individuals' data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis.

CONCLUSIONS: This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.}, } @article {pmid39423759, year = {2024}, author = {Garbsch, R and Schäfer, H and Mooren, FC and Schmitz, B}, title = {Analysis of fat oxidation capacity during cardiopulmonary exercise testing indicates long-lasting metabolic disturbance in patients with post-covid-19 syndrome.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {26-35}, doi = {10.1016/j.clnu.2024.10.010}, pmid = {39423759}, issn = {1532-1983}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Exercise Test/methods ; Exercise Tolerance/physiology ; *Fatigue/physiopathology/etiology ; Lipid Metabolism ; Mitochondria/metabolism ; *Oxidation-Reduction ; *Post-Acute COVID-19 Syndrome/complications/physiopathology ; Prospective Studies ; }, abstract = {BACKGROUND & AIMS: Post-COVID-19 Syndrome (PCS) is characterized by symptoms including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. The mechanisms underlying the onset and severity of PCS point to mitochondrial dysfunction as significant contributor. This study examined fat oxidation as a function of mitochondrial capacity during exercise.

METHODS: Single-center prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and assessment of fatigue using questionnaires were performed at admission and discharge. Detailed spirometric breath-by-breath data were used to calculate substrate oxidation rates.

RESULTS: Patients (N = 187; 38 % women; 49.7 ± 11.4 years) were referred to rehabilitation 253.4 ± 130.6 days after infection. Lead symptoms included fatigue/exercise intolerance (79.9 %), shortness of breath (77.0 %), and cognitive dysfunction (55.1 %). Fat oxidation capacity was disturbed in PCS patients overall (AUC: 11.3 [10.7-11.9]) compared to healthy controls (p < 0.0001), with hospitalization during acute infection predicting the level of disturbance (p < 0.0001). Low exercise capacity and high fatigue scores resulted in reduced fat oxidation (both p < 0.0001). In particular, younger males were affected by significantly reduced fat oxidation capacity (sex: p = 0.002; age: p < 0.001). Metabolic disturbance was significantly improved during exercise-based rehabilitation (AUC: 14.9 [14.4-15.4]; p < 0.0001), even for the group of younger impaired males (+44.2 %; p < 0.0001). Carbohydrate oxidation was not impaired.

CONCLUSIONS: PCS-specific restrictions in fat oxidation may indicate persistent mitochondrial dysfunction. Clinical assessment of PCS patients should include detailed breath-by-breath analysis during exercise to identify metabolic alterations especially in the group of younger males identified in this report. Exercise-based rehabilitation results in improved exercise capacity and fat oxidation and thus likely mitochondrial function.

CLINICAL TRIALS: NCT06468722.}, } @article {pmid39423742, year = {2024}, author = {Zhou, M and Zhu, Q and Xu, Y and Zhou, Z and Guo, C and Lin, Z and Zhang, X and Yang, Z and Li, X and Lin, W}, title = {A nomogram to predict long COVID risk based on pre- and post-infection factors: Results from a cross-sectional study in South China.}, journal = {Public health}, volume = {237}, number = {}, pages = {176-183}, doi = {10.1016/j.puhe.2024.09.023}, pmid = {39423742}, issn = {1476-5616}, mesh = {Humans ; *COVID-19/epidemiology ; Cross-Sectional Studies ; China/epidemiology ; Male ; Female ; Middle Aged ; *Nomograms ; Retrospective Studies ; Risk Factors ; Adult ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Long COVID has received much attention as a complex multi-system disease due to its serious impact on quality of life. However, there remains inconsistent results in terms of risk factors, and a prediction model for the accurate prediction of long COVID is still lacking.

STUDY DESIGN: Cross-sectional study.

METHODS: In this retrospective study, a community population from the Futian District of Shenzhen, Guangdong Province, China, were included. Data were collected from September to December 2023 using an electronic questionnaire. Logistic regression analyses were used to identify predictors of long COVID. Pre-infection and post-infection prediction models (with/without post-infection characteristics) were developed, and the C-index was used to evaluate accuracy.

RESULTS: In total, 420 patients infected COVID-19 were included. The prevalence of long COVID was 32.9 %. The most common symptoms of long COVID were weakness/fatigue, persistent cough and cognitive dysfunction. Independent predictors of long COVID included in the pre-infection model were age, long-term medication, and psychological problems such as stress and doing things without enthusiasm/interest before COVID-19 infection (C-index: 0.721). Independent predictors included in the post-infection model were age, inability to concentrate before COVID-19 infection, and symptoms of weakness/fatigue, abnormal smell/taste, diarrhoea, eye conjunctivitis and headache/dizziness during the acute-phase (C-index: 0.857).

CONCLUSIONS: Age, psychological problems before COVID-19 infection and acute-phase symptoms were important risk factors of long COVID. Results from the pre-infection model provide guidance for non-infected individuals on how to prevent long COVID. Results from the post-infection model can be used to accurately predict individuals who are at high risk of long COVID and help design treatment plans for patients in the acute phase.}, } @article {pmid39422912, year = {2024}, author = {Rothman, RL and Stewart, TG and Mourad, A and Boulware, DR and McCarthy, MW and Thicklin, F and Garcia Del Sol, IT and Garcia, JL and Bramante, CT and Shah, NS and Singh, U and Williamson, JC and Rebolledo, PA and Jagannathan, P and Schwasinger-Schmidt, T and Ginde, AA and Castro, M and Jayaweera, D and Sulkowski, M and Gentile, N and McTigue, K and Felker, GM and DeLong, A and Wilder, R and Collins, S and Dunsmore, SE and Adam, SJ and Hanna, GJ and Shenkman, E and Hernandez, AF and Naggie, S and Lindsell, CJ and , }, title = {Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo: The ACTIV-6 Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {7}, number = {10}, pages = {e2439332}, pmid = {39422912}, issn = {2574-3805}, mesh = {Humans ; *Acetates/therapeutic use ; Female ; Male ; *Sulfides ; *Quinolines/therapeutic use ; *Cyclopropanes/therapeutic use ; Middle Aged ; *COVID-19 Drug Treatment ; *COVID-19 ; *SARS-CoV-2 ; Adult ; Outpatients/statistics & numerical data ; Hospitalization/statistics & numerical data ; Treatment Outcome ; Aged ; Double-Blind Method ; Leukotriene Antagonists/therapeutic use ; }, abstract = {IMPORTANCE: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain.

OBJECTIVE: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.

This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites.

INTERVENTIONS: Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis.

RESULTS: Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04885530.}, } @article {pmid39421860, year = {2024}, author = {Saloma, CP and Ayes, MEC and Taracatac, PS and Asa, MRQ}, title = {Long-term COVID-19 sequelae by Theta and SARS-CoV-2 variants in a Philippine cohort.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1455729}, pmid = {39421860}, issn = {2296-858X}, abstract = {INTRODUCTION: Millions have been infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since its emergence in 2019, but most patients make a full recovery. The long-term consequences of the infection are anticipated to unravel in the succeeding years with reports of patients experiencing chronic, debilitating sequelae post-infection commonly referred to as Long COVID. Various Variants of Concern (VoCs) have emerged as the SARS-CoV-2 virus evolved displaying increased infectivity and immune evasiveness. We investigate whether the infecting VoCs affect the sequelae of Long COVID in a Philippine cohort.

METHODS: SARS-CoV-2 cases confirmed using RT-PCR followed by Next Generation Sequencing were identified from selected regions of the Philippines and recruited through a retrospective-prospective cohort design. Participants were divided based on the initial infecting VoC or Variant of Interest (VoI) and were subsequently interviewed regarding the presence, intensity, and frequency of key Long COVID symptoms, and followed up on two more separate sessions at least three (3) months apart for a total of three (3) data collection points (S1, S2, S3) to document changes in symptoms throughout the year-long study period.

RESULTS: Long COVID symptoms were reported in 88, 82, and 68% of participants in S1, S2, and S3, respectively, showing declining incidence with elapsed time since the first reported infection. General symptoms including headache, fatigue, and post-exertional malaise were the most frequently reported symptoms, while neuropsychiatric symptoms were the second most frequently reported symptoms. In all three (3) sessions, intermittent brain fog, fatigue, and headache were the most frequently reported symptoms in all SARS-CoV-2 variant cohorts. Factors such as age, sex, comorbidities, and disease severity influenced symptom frequency, providing insight into the risk factors that contribute to the prevalence of this disease.

CONCLUSION: A large proportion (>68%) of cases in this Philippine cohort previously infected with different SARS-CoV-2 variants presented with long-term complications of COVID-19 characterized by a highly heterogeneous set of debilitating symptoms. The study highlights the need for long-term monitoring of Long COVID and its impact on human health and the need for our health systems to adopt policy response strategies.}, } @article {pmid39420307, year = {2024}, author = {Krongthaeo, S and Partiprajak, S and Piaseu, N and Ckumdee, S and Taaon, C and Kongsuwan, A}, title = {Prevalence and exploratory factor analysis of long COVID-19 symptoms among experienced infected population in Bangkok, Thailand.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2863}, pmid = {39420307}, issn = {1471-2458}, mesh = {Humans ; Thailand/epidemiology ; Female ; Male ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; Prevalence ; Factor Analysis, Statistical ; Severity of Illness Index ; Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; SARS-CoV-2 ; Fatigue/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Patients with long COVID may experience various concomitant symptoms caused by inflammation, which affect their lives and well-being. In this study, we aimed to (1) investigate the prevalence of long COVID; (2) explore the levels of symptom severity and functional disability owing to long COVID, overall health, and their relationship; and (3) conduct exploratory factor analysis of long COVID-19 symptoms among experienced infected population in the capital of Thailand.

METHODS: A cross-sectional research design was used and a sample of 337 community members with previously COVID-19 infection in Bangkok, Thailand was recruited for this study. Purposive sampling was used. Data collection was performed using an online and a paper-based questionnaire. Descriptive statistics (number, percentage), odds ratio, exploratory factor analysis, and Spearman's rank correlation coefficient were used for the data analysis.

RESULTS: The prevalence of long COVID was 32.9%. The main reported symptoms included anxiety (28.5%), fatigue (26.1%), and dyspnea (13.4%). There was a significant relationship between symptom severity and functional disability (rs=0.385, p value < 0.01). Overall health was negatively correlated with symptom severity (rs = - 0.291, p < .01) and functional disability (rs = - 0.108, p < .05). Using principal component analysis with Promax rotation, three clusters were identified, explaining 71.44% of the total variance. The Clusters comprised (1) common symptoms of long COVID and communication, (2) fatigue, functioning, and nutritional concerns, and (3) psychosocial impacts.

CONCLUSIONS: The present results might help multidisciplinary care teams understand the concurrent symptoms of patients with long COVID and develop rehabilitation care programs to ease all symptoms simultaneously and improve patients' quality of life.}, } @article {pmid39419616, year = {2024}, author = {Adeyinka, DA and Amah, A and Husband, A and Miller, L and Hedlund, D and Alphonsus, KB and Groot, G}, title = {Mapping the landscape of mental health and long COVID: a protocol for scoping review.}, journal = {BMJ open}, volume = {14}, number = {10}, pages = {e087436}, pmid = {39419616}, issn = {2044-6055}, mesh = {Humans ; Mental Disorders/epidemiology/therapy ; *Mental Health ; *Post-Acute COVID-19 Syndrome/epidemiology/psychology ; Research Design ; SARS-CoV-2 ; Systematic Reviews as Topic ; Review Literature as Topic ; }, abstract = {INTRODUCTION: Mental health concerns are prevalent among adult patients with long COVID (LC), but the current state of knowledge regarding mental health in the context of LC is not fully understood. The objective of this scoping review is to map and summarise the existing research on mental health conditions among LC patients and highlight the knowledge gaps. This review aims to provide a comprehensive overview of the evolving landscape of research in the area.

METHODS AND ANALYSIS: The concept of interest is mental health in adult LC patients. This scoping review will be guided by the Joanna Briggs Institute Manual for Evidence Synthesis and reported according to the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines. Using predefined search parameters, a comprehensive search of two electronic databases (Medline and APA PsycINFO) and grey literature sources identified 3104 potentially eligible articles published from 1 January 2020 to 4 April 2024. Following the removal of duplicates, 2767 articles were imported for screening in Covidence. The study selection process involves screening titles, abstracts and full text of potentially relevant articles, which will then be analysed using thematic analysis. Data will be extracted using a predefined extraction form.

ETHICS AND DISSEMINATION: Ethical approval is not required because this study does not involve human participants or primary data collection. The findings from this review will be disseminated through a peer-reviewed publication, conference presentations and professional networks. In addition, a summary of the results will be shared with patient partners and other relevant stakeholders.

PUBLIC HEALTH IMPLICATIONS: The findings from this scoping review will contribute to a better understanding of mental health issues arising in LC patients and inform future research directions and public health interventions in this area.}, } @article {pmid39419470, year = {2024}, author = {Brunel, J and Paganini, J and Galloux, M and Charvet, B and Perron, H}, title = {HERV-W ENV transcription in B cells predicting symptomatic COVID-19 and risk for long COVID can express a full-length protein despite stop codon in mRNA from chromosome X via a ribosome readthrough.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105431}, doi = {10.1016/j.micinf.2024.105431}, pmid = {39419470}, issn = {1769-714X}, abstract = {The human genome comprises 8 % of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-W ENV-U3R RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-W ENV RNA origin in these patients but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.}, } @article {pmid39419167, year = {2024}, author = {Ellingjord-Dale, M and Nygaard, AB and Støer, NC and Bø, R and Landrø, NI and Brunvoll, SH and Istre, M and Kalleberg, KT and Dahl, JA and Geng, L and Tsilidis, K and Riboli, E and Ursin, G and Søraas, A}, title = {Temporal trajectories of long-COVID symptoms in adults with 22 months follow-up in a prospective cohort study in Norway.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {149}, number = {}, pages = {107263}, doi = {10.1016/j.ijid.2024.107263}, pmid = {39419167}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; Norway/epidemiology ; Adult ; Male ; Middle Aged ; Female ; Aged ; Prospective Studies ; Follow-Up Studies ; *SARS-CoV-2 ; Young Adult ; Aged, 80 and over ; Adolescent ; Post-Acute COVID-19 Syndrome ; Fatigue ; Anosmia/epidemiology/physiopathology ; }, abstract = {OBJECTIVES: There is a lack of large studies on long-COVID symptoms with symptoms measurements before the onset of COVID-19. Therefore, long-COVID is still poorly defined.

METHODS: The Norwegian COVID-19 Cohort Study is a population-based, open cohort of adult participants (aged 18-96 years) from Norway. From March 27, 2020, participants were recruited through social media, invitations, and nationwide media coverage. Fourteen somatic and cognitive symptoms were assessed at baseline and four follow-ups for up to 22 months. SARS-CoV-2 test status was obtained from a mandatory national registry or from self-report.

RESULTS: After follow-up, 15 737 participants had a SARS-CoV-2-positive test, 67 305 had a negative test, and 37 563 were still untested. Persistent symptoms reported more frequently by positive compared with negative participants one month after infection, were memory problems (3-6 months: adjusted odds ratio (aOR) = 6.8, CI = 5.7-8.1; >18 months: aOR = 9.4, CI = 4.1-22), and concentration problems (3-6 months: aOR = 4.1, CI = 3.5-4.7; >18 months: aOR = 4.4, CI = 2.0-9.7) as well fatigue, dyspnea, anosmia and dysgeusia.

CONCLUSIONS: COVID-19 was associated with cognitive symptoms, anosmia, dysgeusia, dyspnea, and fatigue as well as worsening of overall health up to 22 months after a SARS-CoV-2 test, even when correcting for symptoms before the onset of COVID-19.}, } @article {pmid39418956, year = {2024}, author = {Fuller, T and Flores Mamani, R and Ferreira Pinto Santos, H and Melo Espíndola, O and Guaraldo, L and Lopes Melo, C and Borges Da Silva, MF and Amaral Calvet, G and Soares Bastos, L and Carvalho, MS and Brasil, P}, title = {Sex, vaccination status, and comorbidities influence long COVID persistence.}, journal = {Journal of infection and public health}, volume = {17}, number = {11}, pages = {102562}, doi = {10.1016/j.jiph.2024.102562}, pmid = {39418956}, issn = {1876-035X}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/immunology ; Prospective Studies ; Adult ; Middle Aged ; *SARS-CoV-2/immunology ; *Comorbidity ; Risk Factors ; Sex Factors ; *Immunoglobulin G/blood ; Fatigue/epidemiology ; Antibodies, Viral/blood ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BACKGROUND: There is interest in the public health impact of Long COVID, defined as symptoms that persist or begin after SARS-CoV-2 infection. We aimed to identify demographic and clinical risk factors associated with Long COVID over time in an Upper Middle-Income Country (UMIC) and potential biomarkers predictive of symptom trajectory.

METHODS: Prospective cohort study of adults with mild SARS-COV-2 during the Omicron period. We tracked symptom persistence and IgG antibody titers against the spike S1 subunit.

RESULTS: Of 383 participants, 276 had confirmed SARS-CoV-2 infection. Long COVID persisted for ≥ two months in 21 % and ≥ 12 months in 5 %. The most common symptoms were fatigue, upper respiratory symptoms, and myalgia/arthralgia: 15 % had fatigue for ≥ one month, 10 % for ≥ two months, and 5 % ≥ three months. Upper respiratory symptoms lasted ≥ one month in 17 %, ≥ two months in 7 %, and ≥ three months in 3 %. Fully 9 % reported myalgia/arthralgia lasting ≥ one month, 6 % ≥ two months, and 4 % ≥ three months. Risk factors for symptom persistence included female sex, not being fully vaccinated, and comorbidities. Participants experiencing persistent fatigue had lower anti-S1 IgG titers.

CONCLUSIONS: In this population, symptom persistence declined after the acute phase, but 5 % of participants did not fully recover. Even in a population that was almost fully vaccinated, women, individuals with comorbidities, and the few remaining people who were unvaccinated were at greater risk for Long COVID. Immunoglobulins may have utility as a biomarker of Long COVID fatigue in this population.}, } @article {pmid39418782, year = {2025}, author = {Lim, SH and Lim, YC and Ahmad Zaki, R and Megat Johari, B and Chang, CY and Syed Omar, SF and Azzeri, A and Dahlui, M and Kamarulzaman, A}, title = {Effect of Long COVID on Work Performance and Annual Monetary Loss Among Infected Health Care Workers at a Tertiary Hospital in Malaysia.}, journal = {Journal of occupational and environmental medicine}, volume = {67}, number = {1}, pages = {44-50}, doi = {10.1097/JOM.0000000000003256}, pmid = {39418782}, issn = {1536-5948}, mesh = {Humans ; *COVID-19/economics/epidemiology ; Retrospective Studies ; Male ; Female ; *Presenteeism/economics/statistics & numerical data ; Adult ; Malaysia/epidemiology ; *Absenteeism ; *Tertiary Care Centers ; *SARS-CoV-2 ; *Work Performance ; *Health Personnel ; Middle Aged ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The aim of the study is to assess and compare the work performance loss (absenteeism and presenteeism) and the estimated annual monetary loss among health care workers with and without long COVID.

METHODS: A retrospective cohort study was conducted between October 2022 and April 2024 using an online questionnaire. The shortened version of the Health and Work Performance Questionnaire was used to estimate the work performance effect among health care workers with a history of COVID-19 infection.

RESULTS: Health care workers with long COVID have a significantly lower absolute presenteeism and higher annual monetary loss of presenteeism. The mean annual monetary loss of presenteeism was higher in those with long COVID (MYR 10,866.61) compared to those without (MYR 9243.85).

CONCLUSIONS: Implementing supportive work strategies in hospital settings is recommended to reduce absolute presenteeism and the annual monetary loss of presenteeism.}, } @article {pmid39418080, year = {2024}, author = {Wu, M and Yan, J and Qiao, C and Yan, C}, title = {Impact of Concurrent Media Exposure on Professional Identity: Cross-Sectional Study of 1087 Medical Students During Long COVID.}, journal = {Journal of medical Internet research}, volume = {26}, number = {}, pages = {e50057}, pmid = {39418080}, issn = {1438-8871}, mesh = {Humans ; *Students, Medical/psychology/statistics & numerical data ; *COVID-19/psychology/epidemiology ; Cross-Sectional Studies ; *Social Media ; Male ; *Social Identification ; Female ; Social Support ; China ; SARS-CoV-2 ; Young Adult ; Surveys and Questionnaires ; Adult ; Mass Media/statistics & numerical data ; Pandemics ; Media Exposure ; }, abstract = {BACKGROUND: Long COVID has widened the health gap across society and highlighted the vulnerabilities and risks faced by health care systems. For instance, the global trend of medical workers resigning has become a prominent topic on social media. In response to this severe social problem in global public health within the digital society, it is urgent to investigate how the professional identity of medical students, who are digital natives and the future workforce of medical practitioners, is affected by the media environment.

OBJECTIVE: This study aims to examine how media exposure relates to medical students' perceptions of informational and emotional support, and how these perceptions further influence the development of their professional identity.

METHODS: Building on the Stimulus-Organism-Response (SOR) framework, this study develops a theoretical model to illustrate how media exposure affects medical students' professional identity through the mediation of social support. Specifically, media exposure was assessed through online news media and social media exposure; social support was evaluated in terms of informational and emotional support; and professional identity was measured through medical students' sense of belonging and professional commitment. A survey was conducted at a medical school in China, yielding 1087 valid responses that were analyzed using SmartPLS 4.0.

RESULTS: Consistent with our expectations, online news media exposure was positively associated with both informational support (β=.163; P<.001) and emotional support (β=.084; P=.007). Similarly, social media exposure showed positive associations with informational support (β=.122; P<.001) and emotional support (β=.235; P<.001). Thereafter, informational support (β=.228; P<.001) and emotional support (β=.344; P<.001) were positively associated with students' sense of belonging. Meanwhile, both informational support (β=.245; P<.001) and emotional support (β=.412; P<.001) positively impacted medical students' professional commitment. In addition, a mediation test was conducted. The results confirmed that informational support and emotional support partially mediated the effect of online news media, while fully mediating the effect of social media on medical students' sense of belonging and professional commitment.

CONCLUSIONS: This study finds that exposure to online news media and social media can enhance medical students' sense of belonging and professional commitment through the formation of informational and emotional support. It expands the discussion on the role of media in providing social support and facilitating the development of medical students' professional identity. This is a valuable contribution to addressing complex public health crises through effective media governance in the network era.}, } @article {pmid39417730, year = {2024}, author = {Stimart, HL and Hipkins, B}, title = {The negative effects of long COVID-19 on cardiovascular health and implications for the presurgical examination.}, journal = {Journal of osteopathic medicine}, volume = {}, number = {}, pages = {}, pmid = {39417730}, issn = {2702-3648}, abstract = {CONTEXT: In 2019, emergence of the novel and communicable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection took scientific communities by surprise and imposed significant burden on healthcare systems globally. Although the advent of this disease piqued the interest of academic centers, healthcare systems, and the general public, there is still much yet to be elucidated regarding epidemiology, pathophysiology, and long-term impacts of coronavirus disease 2019 (COVID-19). It has been established that long COVID-19 can impact multiple organ systems, including the cardiovascular system, unfavorably. Although the pathophysiology of this damage is not well understood, adverse sequelae may range from chest pain and arrhythmias to heart failure (HF), myocardial infarction, or sudden cardiac death. For any postacute COVID-19 patient requiring a surgical procedure, the potential for cardiac injury secondary to long COVID-19 must be considered in the preoperative cardiac examination.

OBJECTIVES: This literature review serves to add to the growing body of literature exploring postacute cardiovascular outcomes of COVID-19, with a focus on presurgical cardiac clearance in the adult patient. Specifically, this review studies the prevalence of cardiovascular symptomatology including chest pain, arrhythmias, blood pressure changes, myo-/pericarditis, HF, cardiomyopathy, orthostatic intolerance, and thromboembolism. Although current evidence is scarce in both quality and quantity, it is the goal that this review will highlight the negative impacts of long COVID-19 on cardiovascular health and encourage providers to be cognizant of potential sequelae in the context of the presurgical examination.

METHODS: For this study, peer-reviewed and journal-published articles were selected based on established inclusion and exclusion criteria to address the question "How does long COVID-19 impact the presurgical cardiac examination of an adult scheduled to undergo a noncardiac procedure?" Inclusion criteria included human studies conducted in adult patients and published in peer-reviewed journals up until May 2024 examining the effects of long-COVID-19 infection on the cardiovascular system. Exclusion criteria eliminated unpublished reports, preprints, duplicate articles, literature regarding coronavirus strains other than COVID-19, studies regarding post-COVID-19 vaccination complications, animal studies, and studies conducted in people younger than 18 years of age. A total of 6,675 studies were retrieved from PubMed and Google Scholar. Following screening, 60 studies were included in final consideration.

RESULTS: Cardiovascular symptoms of postacute COVID-19 infection were encountered with the following percentages prevalence (total numbers of articles mentioning symptom/total number of articles [60]): chest pain (83.3), arrhythmias (88.3), hypertension (40.0), hypotension (16.7), myocarditis (80.0), pericarditis (51.7), HF (70.0), cardiomyopathy (55.0), orthostatic intolerance (56.7), and thromboembolic events (85.0).

CONCLUSIONS: The presence of persisting COVID symptoms may negatively impact the patient's physical examination, blood tests, electrocardiogram (ECG), imaging, and/or echocardiogram. Cardiac conditions associated with long COVID require special attention in the context of the presurgical candidate due to an increased risk of sudden cardiac death, myocarditis, stroke, and myocardial infarction - even in those who were healthy prior to acute COVID-19 infection. Until more specific scientific evidence comes to light, care of these patients should be viewed through the prism of the best practices already in use and clinicians should maintain a low threshold to pursue more extensive cardiac workup prior to surgery.}, } @article {pmid39417642, year = {2024}, author = {Feuth, T}, title = {Interactions between sleep, inflammation, immunity and infections: A narrative review.}, journal = {Immunity, inflammation and disease}, volume = {12}, number = {10}, pages = {e70046}, pmid = {39417642}, issn = {2050-4527}, mesh = {Humans ; *Inflammation/immunology ; *Sleep/immunology ; *Infections/immunology ; Immunity, Innate ; Animals ; Sleep Wake Disorders/immunology ; }, abstract = {BACKGROUND: Over the past decades, it has become increasingly evident that sleep disturbance contributes to inflammation-mediated disease, including depression, mainly through activation of the innate immune system and to an increased risk of infections.

METHODS: A comprehensive literature search was performed in PubMed to identify relevant research findings in the field of immunity, inflammation and infections, with a focus on translational research findings from the past 5 years.

RESULTS: Physiological sleep is characterized by a dynamic interplay between the immune system and sleep architecture, marked by increased innate immunity and T helper 1 (Th1) -mediated inflammation in the early phase, transitioning to a T helper 2 (Th2) response dominating in late sleep. Chronic sleep disturbances are associated with enhanced inflammation and an elevated risk of infections, while other inflammatory diseases may also be affected. Conversely, inflammation in response to infection can also disrupt sleep patterns and architecture. This narrative review summarizes current data on the complex relationships between sleep, immunity, inflammation and infections, while highlighting translational aspects. The bidirectional nature of these interactions are addressed within specific conditions such as sleep apnea, HIV, and other infections. Furthermore, technical developments with the potential to accelerate our understanding of these interactions are identified, including advances in wearable devices, artificial intelligence, and omics technology. By integrating these tools, novel biomarkers and therapeutic targets for sleep-related immune dysregulation may be identified.

CONCLUSION: The review underscores the importance of understanding and addressing immune imbalance related to sleep disturbances to improve disease outcomes.}, } @article {pmid39416495, year = {2024}, author = {Kaddoussi, R and Rejeb, H and Kalai, A and Zaara, E and Rouetbi, N and Salah Frih, ZB and Zmijewski, P and Ben Saad, H}, title = {Effects of a cardiopulmonary rehabilitation programme on submaximal exercise in Tunisian patients with long-COVID19: A randomized clinical trial.}, journal = {Biology of sport}, volume = {41}, number = {4}, pages = {197-217}, pmid = {39416495}, issn = {0860-021X}, abstract = {There is a lack of randomized clinical trials (RCTs) exploring the outcomes of cardiopulmonary rehabilitation programmes (CPRPs) on submaximal aerobic capacity of long COVID-19 patients (LC19Ps). This RCT aimed to evaluate the effect of an ambulatory CPRP on the 6-min walk test (6MWT) data (main outcome: 6-min walk distance (6MWD)) of LC19Ps. Conducted as a single-blinded RCT, the study included Tunisian LC19Ps with persistent dyspnoea (i.e. modified medical research council (mMRC) level ≥2) at least three months postdiagnosis. LC19Ps were randomly assigned to the intervention (IG, n = 20) or control (CG, n = 10) groups. Pre- and post-CPRP evaluations included dyspnoea assessments (Borg and mMRC scales), anthropometric data, spirometry, and 6MWT. The CPRP (i.e. 18 sessions over six weeks) encompassed warm-up, aerobic training, resistance training, respiratory exercises, and therapeutic education. The CPRP significantly improved i) dyspnoea, i.e. IG exhibited larger reductions compared to the CG in Borg (-3.5 ± 2.0 vs. -1.3 ± 1.5) and mMRC (-1.5 ± 0.8 vs. -0.1 ± 0.3) scales, and ii) 6MWD, i.e. IG demonstrated larger improvements compared to the CG in 6MWD (m, %) (168 ± 99 vs. 5 ± 45 m, 28 ± 8 vs. 1 ± 8%, respectively), and resting heart rate (bpm, % maximal predicted heart rate) (-9 ± 9 vs. 1 ± 7 bpm; -5 ± 6 vs. 0 ± 4%, respectively), with small effect sizes. In the IG, the 1.5-point decrease in mMRC and the 168 m increase in 6MWD exceeded the recommended minimal clinical important differences of 1 point and 30 m, respectively. CPRP appears to be effective in enhancing the submaximal exercise capacity of LC19Ps, particularly in improving 6MWD, dyspnoea, and resting heart rate. RCT registration: www.pactr.org; PACTR202303849880222.}, } @article {pmid39415747, year = {2024}, author = {Grout, L}, title = {Use of Complementary and Integrative Health Approaches in Adults with Long COVID in the US, a Nationally Representative Survey.}, journal = {Journal of integrative and complementary medicine}, volume = {}, number = {}, pages = {}, doi = {10.1089/jicm.2024.0283}, pmid = {39415747}, issn = {2768-3613}, abstract = {Background: Long COVID is a serious, complex condition that has affected the lives of millions of people globally. Complementary and integrative health (CIH) approaches offer a wide range of potential therapies for the management of long COVID symptoms. However, there is limited information available about the utilization of CIH among long COVID patients. Methods: Nationally representative cross-sectional data from the United States 2022 National Health Interview Survey (NHIS, response rate 47.7%, n = 27,651) were used to investigate prevalence and predictors of CIH use in the past 12 months among individuals who experienced long COVID. The 12-month prevalence of CIH use was descriptively analyzed for those with long COVID versus those without using chi-squared tests or unpaired t-tests. Independent predictors of CIH use among individuals with long COVID were analyzed using a stepwise multiple logistic regression analysis. Results: A weighted total of 17,610,801 US adults (19.7%) who had a confirmed case of coronavirus disease 2019 (COVID-19) developed long COVID symptoms. A slightly greater proportion of individuals with long COVID (44.4%) than those without (40.9%) used CIH approaches in the past 12 months. The most used approaches were meditation, yoga, and massage therapy. CIH use by those with long COVID was significantly associated with younger age, female sex, higher education level, having health insurance coverage, higher household income level, receiving three or more COVID-19 vaccination doses, ever having asthma, and ever having an anxiety or depression diagnosis. Conclusions: Long COVID represents a major challenge for patients, health care providers, health care systems, economies, and global public health. CIH approaches may play an important role in symptom management for some patients, and additional research is needed to identify which modalities are most effective. Patients and health care providers may benefit from better information about the available options for treatment.}, } @article {pmid39415455, year = {2024}, author = {Wu, TY and Hoffman, JL and Lally, S and Hartl, B and Malinowski-Fahner, T and Roche, R and Washington, VL and Yang, J}, title = {Training Community Health Workers to Respond to Public Health Demands.}, journal = {Journal of community health nursing}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/07370016.2024.2403555}, pmid = {39415455}, issn = {1532-7655}, abstract = {BACKGROUND: Community health workers (CHWs) connect individuals to community resources and build individual competence in an effort to improve overall community/public health. There is a need for more research on how community health nurse (CHN)-led training programs are needed to help train and support CHWs.

PURPOSE: The purpose was to describe the development and evaluation of a series of CHN-led CHW trainings on CHW role, boundaries, and motivational interviewing; diabetes; mental health and long COVID; sexually transmitted infections; and lead poisoning prevention and treatment.

DESIGN: This study utilized a one-group pretest-posttest design in which quantitative and qualitative data were collected.

METHODS: The sample consisted of CHWs representing White/Caucasian, Black/African American, Hispanic/Latinx, and Asian American populations who for each topic, completed a pretest one week prior to the training, the training, and a posttest one week after the training. The quantitative and qualitative data collected during winter and spring/summer 2023 underwent statistical and thematic analysis, respectively.

FINDINGS: The results suggest that the CHW trainings were effective overall at increasing participants' knowledge and confidence in their knowledge levels, as well as comfort with educating community members on various public health topics. Information learned and found most helpful, and application and utilization plans for this knowledge in their work were revealed.

CONCLUSIONS: CHWs are important for disseminating health communication and education among members of their communities, and play a key role in reducing health disparities among at-risk populations.

CLINICAL EVIDENCE: CHN-led educational intervention is a strategy to improve CHWs' knowledge, confidence, and comfort.}, } @article {pmid39409138, year = {2024}, author = {Kell, DB and Pretorius, E}, title = {Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39409138}, issn = {1422-0067}, mesh = {Humans ; *Proteomics/methods ; *Amyloid/metabolism ; Amyloidosis/metabolism ; Fibrin/metabolism ; Proteome/metabolism ; Amyloidogenic Proteins/metabolism ; Blood Coagulation ; }, abstract = {In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena can occur in blood from individuals with circulating inflammatory molecules (and also some originating from viruses and bacteria). Such pathological clotting can result in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We thus provide evidence against such a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant quantitative overlap with the normal plasma proteome and no correlation between plasma protein abundance and their presence in fibrinaloid microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand factor are well represented. Using bioinformatic tools, including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots' resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders.}, } @article {pmid39407877, year = {2024}, author = {Bodey, R and Grimaldi, J and Tait, H and Godfrey, B and Witton, S and Shardha, J and Tarrant, R and Sivan, M}, title = {How Long Is Long COVID? Evaluation of Long-Term Health Status in Individuals Discharged from a Specialist Community Long COVID Service.}, journal = {Journal of clinical medicine}, volume = {13}, number = {19}, pages = {}, pmid = {39407877}, issn = {2077-0383}, abstract = {Background: Post COVID-19 syndrome or long COVID (LC) is a novel fluctuating condition with a protracted course in some patients. Specialist LC services have been operational in the UK since 2020 and deal with a high caseload of patients. Aims: To evaluate long-term outcomes in patients discharged from a community-based LC specialist service. Methods: A service evaluation study that included patients who were well engaged in the services [completed the standard Patient Reported Outcome Measures (PROMs) and received intervention from clinician(s)] and had been discharged for at least 3 months from the service. They consented to the study and completed standard PROMs: COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), EQ-5D-5L and National Institute for Health and Care Excellence (NICE) criteria for myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS). Results: Out of 460 patients contacted, 112 (average of 37.6 months since infection and 9.8 months post-discharge) completed the PROMs. Of these, 90.2% patients continued to experience LC symptoms and disability and had not returned to their pre-COVID-19 health status. The average EQ-5D-5L index score was 0.53 (SD 0.29), highlighting a significant disability and that LC had become a long-term condition (LTC) in the majority of patients who responded to the survey. Of these patients, 43% met the criteria for suspected ME/CFS. Conclusions: A proportion of LC patients develop persistent long COVID (PLC) consistent with a LTC and had a significant overlap with ME/CFS.}, } @article {pmid39404791, year = {2024}, author = {Martini, AL and Carli, G and Caminiti, SP and Kiferle, L and Leo, A and Perani, D and Sestini, S}, title = {Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {}, number = {}, pages = {}, pmid = {39404791}, issn = {1619-7089}, abstract = {PURPOSE: Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients.

METHODS: We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent FDG-PET scans, and classified to timing infection as follows: acute (7 pts), subacute (17 pts), long-term (20 pts) phases. Interregional correlation analysis (IRCA) and ROI-based IRCA were applied on FDG-PET data to extract metabolic connectivity in resting state networks (ADMN, PDMN, EXN, ATTN, LIN, ASN) of neuro-COVID pts in acute/subacute and long-term groups compared with healthy controls (HCs). Univariate approach was used to investigate metabolic alterations from the acute to sub-acute and long-term phase.

RESULTS: The acute/subacute phase was characterized by hyperconnectivity in EXN and ATTN networks; the same networks showed hypoconnectivity in the chronic phase. EXN and ATTN hypoconnectivity was consistent with clinical findings in long-COVID patients, e.g. altered performances in neuropsychological tests of executive and attention domains. The ASN and LIN presented hyperconnectivity in acute/subacute phase and normalized in long-term phase. The ADMN and PDMN presented a preseverved connectivity. Univariate analysis showed hypometabolism in fronto-insular cortex in acute phase, which reduced in sub-acute phase and disappeared in long-term phase.

CONCLUSION: A compensatory EXN and ATTN hyperconnectivity was found in the acute/subacute phase and hypoconnectivity in long-term. Hypoconnectivity and absence of hypometabolism suggest that connectivity derangement in frontal networks could be related to protraction of neurological symptoms in long-term COVID patients.}, } @article {pmid39403255, year = {2024}, author = {Kempuraj, D and Tsilioni, I and Aenlle, KK and Klimas, NG and Theoharides, TC}, title = {Long COVID elevated MMP-9 and release from microglia by SARS-CoV-2 Spike protein.}, journal = {Translational neuroscience}, volume = {15}, number = {1}, pages = {20220352}, pmid = {39403255}, issn = {2081-3856}, abstract = {OBJECTIVE: Long COVID is a major health concern because many patients develop chronic neuropsychiatric symptoms, but the precise pathogenesis is unknown. Matrix metalloproteinase-9 (MMP-9) can disrupt neuronal connectivity and be elevated in patients with long COVID.

METHODS: In this study, MMP-9 was measured in the serum of long COVID patients and healthy controls, as well as in the supernatant fluid of cultured human microglia cell line stimulated by recombinant severe acute respiratory syndrome coronavirus 2 Spike protein, as well as lipopolysaccharide (LPS) and neurotensin (NT) used as positive controls. MMP-9 was measured by commercial enzyme-linked immunosorbent assay.

RESULTS: MMP-9 was significantly elevated in the serum of long COVID patients compared to healthy controls. Moreover, there was significant release of MMP-9 from a cultured human microglia cell line stimulated by LPS, NT, or Spike protein. We further show that pretreatment with the flavonoids luteolin and tetramethoxyluteolin (methlut) significantly inhibited the release of MMP-9 stimulated by the Spike protein.

CONCLUSION: MMP-9 from Spike protein-stimulated microglia could contribute to the development of long COVID and may serve as a target for treatment including the use of luteolin.}, } @article {pmid39402811, year = {2024}, author = {Chang, KC and Ahorsu, DK and Tsai, HC and Strong, C and Ko, NY and Chen, JS and Yen, CF and Üztemur, S and Griffiths, MD and Lin, CY}, title = {Parallel Mediating Effects of Sleep Quality, Psychological Distress, and Self-Stigma in the Associations Between Long COVID Symptoms and Quality of Life Among Taiwanese Individuals With Mental Health Illness.}, journal = {Brain and behavior}, volume = {14}, number = {10}, pages = {e70094}, pmid = {39402811}, issn = {2162-3279}, support = {NSTC112-2321-B-006-008//National Science and Technology Council, Taiwan/ ; NSTC112-2314-B-695-001//National Science and Technology Council, Taiwan/ ; TCRD111A069//Tzu-Chi General Hospital/ ; //Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK)/ ; }, mesh = {Humans ; *Quality of Life/psychology ; Male ; Taiwan/epidemiology ; *COVID-19/psychology/epidemiology ; Female ; Middle Aged ; Adult ; *Psychological Distress ; *Social Stigma ; *Sleep Quality ; *Mental Disorders/psychology/physiopathology/epidemiology ; Aged ; Post-Acute COVID-19 Syndrome ; Self Concept ; SARS-CoV-2 ; Stress, Psychological/psychology ; }, abstract = {BACKGROUND: Long COVID symptoms (i.e., experiencing symptoms of COVID-19 for 3 months post-COVID-19) affect individuals' health and their quality of life (QoL). However, the pathways through which it does so are not fully known.

AIM: The present study examined the mediating roles of sleep quality, psychological distress, and self-stigma in the associations between long COVID symptoms and QoL among individuals with mental illness.

METHOD: Individuals with mental illness (n = 333) were recruited from a psychiatric center in southern Taiwan to participate in the study. Data were collected regarding sleep quality, psychological distress, self-stigma, and QoL. Independent t-tests, Pearson correlations, and regression with Hayes' Process Macro were used to compare groups, examine relationships, and parallel mediation models, respectively.

RESULTS: Participants with long COVID symptoms had significantly worse sleep quality, psychological distress, physical QoL, and psychological QoL compared to those without symptoms. There were significant relationships between sleep quality, psychological distress, self-stigma, and QoL. Sleep quality significantly mediated the associations between long COVID symptoms and physical and social QoL. Psychological distress significantly mediated the associations between long COVID symptoms and all domains of QoL, but not self-stigma.

CONCLUSION: There are alternative pathways (e.g., sleep quality and psychological distress) through which long COVID symptoms may affect the QoL of individuals with mental illness. The findings suggest that individuals with long COVID symptoms have a higher chance of having poor QoL. Therefore, there may be the need for counseling and possible therapy for those who contract COVID-19, especially among individuals who already have mental illness.}, } @article {pmid39402206, year = {2024}, author = {Thomas, D and Noishiki, C and Gaddam, S and Wu, D and Manhas, A and Liu, Y and Tripathi, D and Kathale, N and Adkar, SS and Garhyan, J and Liu, C and Xu, B and Ross, EG and Dalman, RL and Wang, KC and Oro, AE and Sallam, K and Lee, JT and Wu, JC and Sayed, N}, title = {CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.}, journal = {Nature cardiovascular research}, volume = {3}, number = {10}, pages = {1249-1265}, pmid = {39402206}, issn = {2731-0590}, support = {R01 HL161002/HL/NHLBI NIH HHS/United States ; K01 HL135455/HL/NHLBI NIH HHS/United States ; K99 HL163443-01//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 869015//American Heart Association (American Heart Association, Inc.)/ ; }, mesh = {Humans ; *COVID-19/metabolism/complications ; Animals ; *Angiotensin-Converting Enzyme 2/metabolism/genetics ; *Chemokine CCL2/metabolism/genetics ; *SARS-CoV-2 ; *Endothelial Cells/metabolism/virology/pathology ; Mice, Transgenic ; Mice ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Aged ; Myocytes, Cardiac/metabolism/virology/pathology ; Organoids/metabolism ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; Heart Diseases/metabolism/pathology/virology/etiology ; }, abstract = {Evidence linking the endothelium to cardiac injury in long coronavirus disease (COVID) is well documented, but the underlying mechanisms remain unknown. Here we show that cytokines released by endothelial cells (ECs) contribute to long-COVID-associated cardiac dysfunction. Using thrombotic vascular tissues from patients with long COVID and induced pluripotent stem cell-derived ECs (iPSC-ECs), we modeled endotheliitis and observed similar dysfunction and cytokine upregulation, notably CCL2. Cardiac organoids comprising iPSC-ECs and iPSC-derived cardiomyocytes showed cardiac dysfunction after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, driven by CCL2. Profiling of chromatin accessibility and gene expression at a single-cell resolution linked CCL2 to 'phenotype switching' and cardiac dysfunction, validated by high-throughput proteomics. Disease modeling of cardiac organoids and exposure of human ACE2 transgenic mice to SARS-CoV-2 spike proteins revealed that CCL2-induced oxidative stress promoted post-translational modification of cardiac proteins, leading to cardiac dysfunction. These findings suggest that EC-released cytokines contribute to cardiac dysfunction in long COVID, highlighting the importance of early vascular health monitoring in patients with long COVID.}, } @article {pmid39402205, year = {2024}, author = {Foster, SR and Hudson, JE}, title = {Endothelial cells as paracrine mediators of long COVID.}, journal = {Nature cardiovascular research}, volume = {3}, number = {10}, pages = {1181-1183}, pmid = {39402205}, issn = {2731-0590}, mesh = {Humans ; *COVID-19 ; *Endothelial Cells/virology/metabolism ; *Paracrine Communication ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid39400651, year = {2024}, author = {Alharbi, A and Almogbel, F and Rabbani, U and Memish, ZA}, title = {Long COVID-19 and Coexistence of Fatigue and Depression: A Cross-sectional Study from Saudi Arabia.}, journal = {Journal of epidemiology and global health}, volume = {14}, number = {4}, pages = {1602-1608}, pmid = {39400651}, issn = {2210-6014}, mesh = {Humans ; Female ; Saudi Arabia/epidemiology ; *COVID-19/epidemiology/psychology ; Cross-Sectional Studies ; Male ; *Fatigue/epidemiology/etiology ; Adult ; *Depression/epidemiology/diagnosis ; Middle Aged ; Prevalence ; SARS-CoV-2 ; Comorbidity ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with various manifestations even after infection resolution. This study aimed to assess the prevalence of post-COVID-19 fatigue and its predictors.

METHODS: We conducted a nationwide cross-sectional study among Polymerase Chain Reaction test confirmed COVID-19 cases in Saudi Arabia from July 2021 to February 2022. We collected data through telephonic interviews covering socio-demographics, comorbidities, body mass index, smoking, illness severity, and COVID-19 vaccination status. We assessed fatigue using Fatigue Severity Scale while depression was assessed using Patient Health Questionnaire-2. Logistic regression was employed to analyze the relationship between post-COVID-19 fatigue and depression.

RESULTS: The analysis included 361 participants with a mean age of 37 ± 10.5 years, among whom 43% were female. Approximately 10% had comorbidities, and 21% were current smokers. Nearly two-thirds (68%) of the participants reported mild illness. The prevalence of perceived fatigue was 22.7%, while fatigue measured by the Fatigue Severity Scale was 14.4%. The multivariable logistic regression model revealed that COVID-19 severity and depression were significant predictors of post-COVID-19 fatigue; adjusted odds ratio 1.87 (95% CI: 1.10 to 3.18) and 14.3 (95% CI: 4.55 to 45.0), respectively.

CONCLUSION: Our findings suggest a higher prevalence of perceived fatigue compared to that measured by the Fatigue Severity Scale, underscoring the importance of using a valid assessment tool for fatigue among COVID-19 patients to ensure proper management. The significant association between post-COVID-19 fatigue and depression highlights the need for psychological assessment of COVID-19 patients to enhance their post-infection quality of life.}, } @article {pmid39400062, year = {2024}, author = {Keřková, B and Kolenič, M and Knížková, K and Hrubý, A and Večeřová, M and Šustová, P and Španiel, F and Rodriguez, M}, title = {Exploring the effects of COVID-19 on verbal memory function in schizophrenia: Multiple case study and brief literature review.}, journal = {Applied neuropsychology. Adult}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/23279095.2024.2416061}, pmid = {39400062}, issn = {2327-9109}, abstract = {Individuals recovering from COVID-19 may experience persistent impairment in verbal memory performance, potentially due to illness-related hippocampal injury. Although verbal memory dysfunction is central to schizophrenia, the interactions between this vulnerability and COVID-19 remain unclear, with no imaging studies addressing the issue to-date. To explore this gap and generate hypotheses for future research, we adopted a multiple case study approach. Two pairs of individuals with an ICD-10 diagnosis of schizophrenia were selected, each consisting of one case with a positive COVID-19 anamnesis and one without. We calculated the Reliable Change Index to estimate the clinical significance of verbal memory performance changes, with annualized change rates in hippocampal volumes assessed against normative data. Compared to their matches, COVID-19 positive cases did not show mutually consistent changes in verbal memory performance: one case experienced a significant decline in verbal memory and learning, while the other showed a general normalization of test scores. Left hippocampal volumes showed a comparatively slowed increase, while the right hippocampi decreased in volume, although these atrophy rates did not exceed those expected in general population samples. Based on these findings, we hypothesize that COVID-19 alone does not lead to verbal memory decline in schizophrenia. Instead, the relationship between the diseases may depend on additional factors. Our case pairs differed in body mass index, systolic blood pressure, sex, phase of illness, and whole grey matter volume trajectories, leading us to hypothesize that these variables represent additional predictors or moderators of this relationship.}, } @article {pmid39399934, year = {2024}, author = {Mirofsky, M and Catalano, H}, title = {Long COVID: a new disease?.}, journal = {Medicina}, volume = {84}, number = {5}, pages = {937-945}, pmid = {39399934}, issn = {1669-9106}, mesh = {Humans ; *COVID-19/complications/prevention & control ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chronic Disease ; Fibromyalgia ; }, abstract = {The definition of quaternary prevention as the set of interventions that avoids or mitigates the consequences of unnecessary or excessive activity of medical interventionism and the health system. The definition of a new disease is a complex process that involves the identification, characterization and description of a medical condition that has not been previously recognized or documented. Since mid-2020, the term chronic COVID/long COVID has been used to describe the presence of signs and symptoms after an acute SARS-CoV-2 infection, with multiple terminologies and definitions in international literature. Post-infectious syndromes, myalgia encephalomyelitis and fibromyalgia, are some of the diseases that have similarities with chronic COVID. This article presents an analysis relating the concepts of new disease and quaternary prevention with chronic COVID and other diseases described in the literature.}, } @article {pmid39399920, year = {2024}, author = {Pignon, B and Wiernik, E and Ranque, B and Robineau, O and Carrat, F and Severi, G and Touvier, M and Gouraud, C and Ouazana Vedrines, C and Pitron, V and Hoertel, N and Kab, S and Tebeka, S and Goldberg, M and Zins, M and Lemogne, C}, title = {SARS-CoV-2 infection and the risk of depressive symptoms: a retrospective longitudinal study from the population-based CONSTANCES cohort.}, journal = {Psychological medicine}, volume = {54}, number = {14}, pages = {1-10}, pmid = {39399920}, issn = {1469-8978}, abstract = {BACKGROUND: Should COVID-19 have a direct impact on the risk of depression, it would suggest specific pathways for prevention and treatment. In this retrospective population-based study, we aimed to examine the association of prior SARS-CoV-2 infection with depressive symptoms, distinguishing self-reported v. biologically confirmed COVID-19.

METHODS: 32 007 participants from the SAPRIS survey nested in the French CONSTANCES cohort were included. COVID-19 was measured as followed: ad hoc serologic testing, self-reported PCR or serology positive test results, and self-reported COVID-19. Depressive symptoms were measured with the Center of Epidemiologic Studies-Depression Scale (CES-D). Outcomes were depressive symptoms (total CES-D score, its four dimensions, and clinically significant depressive symptoms) and exposure was prior COVID-19 (no COVID-19/self-reported unconfirmed COVID-19/biologically confirmed COVID-19).

RESULTS: In comparison to participants without COVID-19, participants with self-reported unconfirmed COVID-19 and biologically confirmed COVID-19 had higher CES-D scores (β for one interquartile range increase [95% CI]: 0.15 [0.08-0.22] and 0.09 [0.05-0.13], respectively) and somatic complaints dimension scores (0.15 [0.09-0.21] and 0.10 [0.07-0.13]). Only those with self-reported but unconfirmed COVID-19 had higher depressed affect dimension scores (0.08 [0.01-0.14]). Accounting for ad hoc serologic testing only, the CES-D score and the somatic complaints dimension were only associated with the combination of self-reported COVID-19 and negative serology test results.

CONCLUSIONS: The association between COVID-19 and depressive symptoms was merely driven by somatic symptoms of depression and did not follow a gradient consistent with the hypothesis of a direct impact of SARS-CoV-2 infection on the risk of depression.}, } @article {pmid39398460, year = {2024}, author = {Chan, HY}, title = {Wearable Devices for Long COVID: Prospects, Challenges and Options.}, journal = {Asian bioethics review}, volume = {16}, number = {4}, pages = {757-769}, pmid = {39398460}, issn = {1793-9453}, abstract = {Post COVID-19 infections resulting in long COVID symptoms remain persistent yet neglected in healthcare priorities. Although long COVID symptoms are expected to decline after some time, many people continue to endure its debilitating effects affecting their daily lives. The diversity of characteristics amongst long COVID patients adds to the complexity of communicating personal health predicaments to healthcare providers. Recent research towards building an evidence base for long COVID with the aim of delivering responsive healthcare interventions for long COVID patients has utilised datasets generated from wearable devices. This paper examines the prospects presented by wearable devices for long COVID patients and physicians. It highlights distinct ethical and legal challenges arising from their use in practice. Several recommendations aiming to support their usage amongst long COVID patients are outlined for future research using wearable devices for long COVID treatment.}, } @article {pmid39398386, year = {2024}, author = {Liu, Y and Lou, X}, title = {The Bidirectional Association Between Metabolic Syndrome and Long-COVID-19.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {3697-3710}, pmid = {39398386}, issn = {1178-7007}, abstract = {BACKGROUND: The rapid global spread of a new coronavirus disease known as COVID-19 has led to a significant increase in mortality rates, resulting in an unprecedented worldwide pandemic.

METHODS: The impact of COVID-19, particularly its long-term effects, has also had a profound effect on the health and well-being of individuals.Metabolic syndrome increases the risk of heart and brain diseases, presenting a significant danger to human well-being.

PURPOSE: The prognosis of long COVID and the progression of metabolic syndrome interact with each other, but there is currently a lack of systematic reports.In this paper, the pathogenesis, related treatment and prognosis of long COVID and metabolic syndrome are systematically reviewed.}, } @article {pmid39396825, year = {2024}, author = {Ramalhosa, F and Lunardi, F and Bernardinello, N and Gori, S and Pezzuto, F and Tauro, V and Del Vecchio, C and Giraudo, C and Balestro, E and Calabrese, F}, title = {Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait.}, journal = {Archives of pathology & laboratory medicine}, volume = {}, number = {}, pages = {}, doi = {10.5858/arpa.2024-0043-OA}, pmid = {39396825}, issn = {1543-2165}, abstract = {CONTEXT.—: Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited.

OBJECTIVE.—: To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised).

DESIGN.—: This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data.

RESULTS.—: Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients.

CONCLUSIONS.—: Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.}, } @article {pmid39395470, year = {2024}, author = {Braga, J and Kuik, EJY and Lepra, M and Rusjan, PM and Kish, SJ and Vieira, EL and Nasser, Z and Verhoeff, N and Vasdev, N and Chao, T and Bagby, M and Boileau, I and Kloiber, S and Husain, MI and Kolla, N and Koshimori, Y and Faiz, K and Wang, W and Meyer, JH}, title = {Astrogliosis Marker [[11]C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms.}, journal = {Biological psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biopsych.2024.09.027}, pmid = {39395470}, issn = {1873-2402}, abstract = {BACKGROUND: After acute COVID-19, 5% of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID, but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective of the current study was to measure [[11]C]SL25.1188 total distribution volume ([[11]C]SL25.1188 VT), an index of monoamine oxidase B density and a marker of astrogliosis, with positron emission tomography in participants with COVID-DC and compare with healthy control participants.

METHODS: In 21 COVID-DC cases and 21 healthy control participants, [[11]C]SL25.1188 VT was measured in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum. Depressive symptoms were measured with the Beck Depression Inventory-II, and cognitive symptoms were measured with neuropsychological tests.

RESULTS: [[11]C]SL25.1188 VT was higher in participants with COVID-DC in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum than in healthy control participants. Depressive symptom severity negatively correlated with [[11]C]SL25.1188 VT across prioritized brain regions. More recent acute COVID-19 positively correlated with [[11]C]SL25.1188 VT, reflecting higher values since predominance of the Omicron variant. Exploratory analyses found greater [[11]C]SL25.1188 VT in the hippocampus, dorsal putamen, and ventral striatum of COVID-DC participants than control participants with a major depressive episode with no history of COVID-19, and there was no relationship to cognitive testing in prioritized regions.

CONCLUSIONS: Results strongly support the presence of monoamine oxidase B-labeled astrogliosis in COVID-DC throughout the regions assessed, although the association of greater astrogliosis with fewer symptoms raises the possibility of a protective role. The magnitude of astrogliosis in COVID-DC is greater since the emergence of the Omicron variant.}, } @article {pmid39388147, year = {2024}, author = {Menson, KE and Dowman, L}, title = {Pulmonary Rehabilitation for Diseases Other Than COPD.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {44}, number = {6}, pages = {425-431}, pmid = {39388147}, issn = {1932-751X}, support = {R01 DA059562/DA/NIDA NIH HHS/United States ; U54 DA036114/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/rehabilitation ; SARS-CoV-2 ; Quality of Life ; Exercise Therapy/methods ; Asthma/rehabilitation/complications ; Exercise Tolerance/physiology ; Hypertension, Pulmonary/rehabilitation/physiopathology ; Pulmonary Disease, Chronic Obstructive/rehabilitation/physiopathology ; Bronchiectasis/rehabilitation/physiopathology ; Lung Neoplasms/rehabilitation/complications ; Lung Diseases/rehabilitation/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Review the current literature regarding pulmonary rehabilitation (PR) for non-chronic obstructive pulmonary disease (COPD) diagnoses and what the evidence is regarding expected outcomes based on disease manifestations. Literature search was performed using PubMed database from March 2024 to June 2024. Terms included "pulmonary rehabilitation" and "exercise training" in conjunction with key words "interstitial lung disease (ILD)," "idiopathic pulmonary fibrosis," "asthma," "bronchiectasis," "post-acute sequalae of SARS-CoV-2 (PASC)," "long COVID," "pulmonary hypertension (PH)," and "lung cancer." Results were filtered for English language, randomized controlled trial, clinical trial, observational trial, meta-analysis, and guidelines. Emphasis was placed on more recent publications since prior reviews, where applicable. The abundance of literature involved ILD, where studies have demonstrated significant improvements in exercise capacity, health-related quality of life (HRQoL), and dyspnea, despite heterogeneity of diseases; benefits are similar to those seen with COPD. Those with milder disease have more sustained benefits longer term. Patients with asthma benefit in severe disease, lower exercise activity, elevated body mass index, or when comorbid conditions are present, and breathing exercises can improve symptoms of breathlessness. Patients with PASC have a multitude of symptoms and lack benefits in HRQoL measurements; PR improves performance on post-COVID-19 functional status scale, a more comprehensive measurement of symptoms. Those with bronchiectasis benefit from PR when airflow limitation or exacerbations are impacting symptoms and HRQoL. Those with stable PH can improve their exertional capacity without change in disease severity. PR reduces perioperative complications in those with lung cancer and preserve fitness during treatment.}, } @article {pmid39393059, year = {2024}, author = {Wiertz, CMH and van Meulenbroek, T and Lamper, C and Hemmen, B and Sep, S and Huijnen, I and Goossens, MEJB and Burgers, J and Verbunt, J}, title = {Effectiveness of a Person-Centered Interdisciplinary Rehabilitation Treatment of Post-COVID-19 Condition: Protocol for a Single-Case Experimental Design Study.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e63951}, pmid = {39393059}, issn = {1929-0748}, mesh = {Humans ; *COVID-19/rehabilitation/psychology ; *Patient-Centered Care ; *Quality of Life/psychology ; Netherlands ; Adult ; Male ; Female ; Activities of Daily Living/psychology ; Middle Aged ; Patient Care Team ; SARS-CoV-2 ; Treatment Outcome ; Research Design ; }, abstract = {BACKGROUND: Patients with post-COVID-19 condition (PCC) experience a wide range of complaints (physical, cognitive, and mental), sometimes with high levels of disability in daily activities. Evidence of effective interdisciplinary rehabilitation treatment is lacking. A person-centered, biopsychosocial, interdisciplinary rehabilitation program, adapted to expert opinions and the patient's needs, was therefore developed.

OBJECTIVE: This study aims to present a study protocol for a clinical trial to evaluate the effect of a new, person-centered, interdisciplinary rehabilitation treatment for PCC. It is aimed at improving participation in society and health-related quality of life in patients with PCC who perceive a high level of disability in daily activities or participation.

METHODS: A total of 20 Dutch adults, aged 18 years or older, with high levels of disability in daily activities and participation in society will be included in this replicated and randomized single-case experimental design study, from October 2023 onward. The replicated and randomized single-case experimental design consists of 3 phases. The baseline phase is the observational period, in which no specific treatment will be given. In the intervention phase, patients will receive the new outpatient treatment 3 times a week for 12 weeks, followed by a 12-week follow-up phase. During the intervention phase, the treatment will be personalized according to the patient's physical, mental, and cognitive symptoms and goals. The treatment team can consist of a rehabilitation physician, physiotherapist, occupational therapist, speech therapist, and psychologist. The primary outcomes of the study are daily diaries, which consist of 8 questions selected from validated questionnaires (Utrecht Scale for Evaluation of Rehabilitation-Participation, EQ-5D-5L, and the Hospital Anxiety and Depression Scale). The other primary outcome measurements are participation in society (Utrecht Scale for Evaluation of Rehabilitation-Participation) and health-related quality of life (EQ-5D-5L). The secondary outcomes are physical tests and validated questionnaires aimed at physical, mental, and cognitive complaints. Effect evaluation based on daily assessments will include visual analysis, calculation of effect sizes (Nonoverlap of All Pairs), randomization tests, and multilevel analysis. In addition, other analyses will be based on ANOVA or a 2-tailed Student t test.

RESULTS: Data collection for this study started in October 2023 and is planned to be completed in July 2024. The results will be published in peer-reviewed journals and presented at international conferences.

CONCLUSIONS: This is the first study investigating the effect of an interdisciplinary rehabilitation treatment with a person-centered, biopsychosocial approach in patients with PCC. Our findings will help to improve the treatment and support of patients with PCC.

TRIAL REGISTRATION: German Clinical Trials Register DRKS00032636; https://drks.de/search/en/trial/DRKS00032636.

DERR1-10.2196/63951.}, } @article {pmid39392878, year = {2024}, author = {Redondo-Calvo, FJ and Rabanal-Ruiz, Y and Verdugo-Moreno, G and Bejarano-Ramírez, N and Bodoque-Villar, R and Durán-Prado, M and Illescas, S and Chicano-Galvez, E and Gómez-Romero, FJ and Martinez-Alarcón, J and Arias-Pardilla, J and Lopez-Juarez, P and Padin, JF and Peinado, JR and Serrano-Oviedo, L}, title = {Longitudinal Assessment of Nasopharyngeal Biomarkers Post-COVID-19: Unveiling Persistent Markers and Severity Correlations.}, journal = {Journal of proteome research}, volume = {23}, number = {11}, pages = {5064-5084}, pmid = {39392878}, issn = {1535-3907}, mesh = {Humans ; *COVID-19/virology/complications/diagnosis ; *Biomarkers/analysis/metabolism ; *Nasopharynx/virology/metabolism ; *Severity of Illness Index ; *SARS-CoV-2/isolation & purification ; Male ; Female ; Longitudinal Studies ; Middle Aged ; Adult ; Aged ; }, abstract = {SARS-CoV-19 infection provokes a variety of symptoms; most patients present mild/moderate symptoms, whereas a small proportion of patients progress to severe illness with multiorgan failure accompanied by metabolic disturbances requiring ICU-level care. Given the importance of the disease, researchers focused on identifying severity-associated biomarkers in infected patients as well as markers associated with patients suffering long-COVID. However, little is known about the presence of biomarkers that remain a few years after SARS-CoV-2 infection once the patients fully recover of the symptoms. In this study, we evaluated the presence of persistent biomarkers in the nasopharyngeal tract two years after SARS-Cov-2 infection in fully asymptomatic patients, taking into account the severity of their infection (mild/moderate and severe infections). In addition to the direct identification of several components of the Coronavirus Infection Pathway in those individuals that suffered severe infections, we describe herein 371 proteins and their associated canonical pathways that define the different adverse effects of SARS-CoV-2 infections. The persistence of these biomarkers for up to two years after infection, along with their ability to distinguish the severity of the infection endured, highlights the surprising presence of persistent nasopharyngeal exudate changes in fully recovered patients.}, } @article {pmid39392635, year = {2024}, author = {Reyes, KP and Rafique, Z and Chinnock, B and Kumar, VA and Gottlieb, M and Rising, KL and Rodriguez, RM}, title = {Long COVID Among Undocumented Latino Immigrant Populations in the Emergency Department.}, journal = {JAMA network open}, volume = {7}, number = {10}, pages = {e2438806}, pmid = {39392635}, issn = {2574-3805}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Emergency Service, Hospital/statistics & numerical data ; *Hispanic or Latino ; *Undocumented Immigrants ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome/ethnology ; }, } @article {pmid39392098, year = {2025}, author = {Silver, SR and Li, J and Ford, ND and Shi, D and Saydah, SH}, title = {Prevalence of COVID-19 and Long COVID by Industry and Occupation: Behavioral Risk Factor Surveillance System 2022.}, journal = {American journal of industrial medicine}, volume = {68}, number = {1}, pages = {26-52}, pmid = {39392098}, issn = {1097-0274}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Behavioral Risk Factor Surveillance System ; Prevalence ; United States/epidemiology ; *Occupations/statistics & numerical data ; Adult ; Male ; Middle Aged ; *Industry/statistics & numerical data ; Female ; SARS-CoV-2 ; Young Adult ; Adolescent ; Guam/epidemiology ; }, abstract = {BACKGROUND: Workers in healthcare and other essential occupations had elevated risks for COVID-19 infection early in the pandemic. No survey of U.S. workers to date has comprehensively assessed the prevalence of both COVID-19 and Long COVID across industries and occupations (I&O) at a detailed level.

METHODS: Behavioral Risk Factor Surveillance System data for 2022 from 39 states, Guam, and the U.S. Virgin Islands were used to estimate prevalence of self-reported history of COVID-19 and Long COVID, as well as the prevalence of Long COVID among those reporting prior COVID-19, by broad and detailed I&O. Adjusted prevalence ratios were used to compare outcome prevalence in each I&O to prevalence among all other workers combined.

RESULTS: By broad I&O, workers in healthcare, protective services, and education had elevated prevalences of COVID-19. The prevalence of Long COVID was elevated in healthcare and protective service but not education workers. Detailed I&O with significantly elevated prevalences of COVID-19 but not Long COVID included Dairy Product Manufacturing industry workers and subsets of mining workers. Both COVID-19 and Long COVID were elevated among bartenders/drinking places and personal care and appearance workers. The prevalence of Long COVID was elevated among farmworkers who reported having had COVID-19.

CONCLUSIONS: Industries and occupations with elevated levels of COVID-19 or Long COVID in this study may warrant increased measures to prevent transmission of airborne respiratory viruses. Accommodations are a key component for supporting workers in all workplaces. This new information about the distribution of Long COVID by I&O suggests where employer understanding and implementation of tailored workplace supports and accommodations are most needed to support continued employment of affected workers.}, } @article {pmid39391784, year = {2024}, author = {Cirkel, A and Göbel, H and Göbel, C and Alkatout, I and Khalil, A and Baum, S and Brüggemann, N and Rody, A and Cirkel, C}, title = {Endometriosis Patients Have an Increased Risk of Experiencing Long-Covid Symptoms: Results from a Cross-Sectional Multicenter Study.}, journal = {Women's health reports (New Rochelle, N.Y.)}, volume = {5}, number = {1}, pages = {671-679}, pmid = {39391784}, issn = {2688-4844}, abstract = {BACKGROUND: Women are more at risk for developing long-term symptoms after a COVID-19 infection. Only limited data are available for patients with coexisting endometriosis and/or menstrual pain symptoms.

STUDY DESIGN: A total of 840 premenopausal women with menstrual pain and/or endometriosis were included in this observational cross-sectional study using an online survey platform.

RESULTS: A total of 840 women with menstrual pain (mean age 30.7 ± 6.9, 15-54 years) were studied. Of these, 714 (84.2%) had a COVID-19 infection, 123 did not (14.5%). A total of 312 subjects had acute COVID-19 (AC) with symptoms ≤4 weeks (43.7%), 132 (18.5%) developed postacute COVID-19 syndrome (PC), and 88 (12.3%) had "long Covid" (LC). There were no statistical differences regarding number of vaccination shots between the three groups AC, PC, and LC. A total of 582 patients with surgically confirmed endometriosis (SCE) showed a twofold increased risk of LC [odds ratio (OR): 2.12, 2.18-3.84] in comparison with AC subjects. In SCE the comorbidity anxiety disorder (OR: 2.08, 1.14-3.81) and depression (OR: 2.02, 1.15-3.56) further increased the risk of LC. LC subjects had a significantly higher disturbance level of menstrual pain (p = 0.002), were more restricted in job (p < 0.001), leisure (p = 0.002), and family activities (p < 0.001), and had a higher number of endometriosis surgeries (p = 0.003).

CONCLUSION: Subjects with SCE had a twofold increased risk of LC (in comparison to subjects with nonconfirmed endometriosis menstrual pain). In patients with SCE concomitant diagnosis of depression or anxiety disorder further twice-fold increased risk of LC. Further studies are needed if it is possible to reduce LC risk by improving the treatment of those secondary diagnoses and whether the type of endometriosis treatment can reduce LC occurrence (holistic, coanalgetic, hormonal).}, } @article {pmid39391697, year = {2024}, author = {Chatatikun, M and Indo, HP and Imai, M and Kawakami, F and Kubo, M and Kitagawa, Y and Ichikawa, H and Udomwech, L and Phongphithakchai, A and Sarakul, O and Sukati, S and Somsak, V and Ichikawa, T and Klangbud, WK and Nissapatorn, V and Tangpong, J and Majima, HJ}, title = {Potential of traditional medicines in alleviating COVID-19 symptoms.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1452616}, pmid = {39391697}, issn = {1663-9812}, abstract = {This review discusses the prevention and treatment of coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in its spike glycoprotein have driven the emergence of variants with high transmissibility and immune escape capabilities. Some antiviral drugs are ineffective against the BA.2 subvariant at the authorized dose. Recently, 150 natural metabolites have been identified as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than those of existing therapeutic agents. Botanical drug-derived bioactive molecules have shown promise in dampening the COVID-19 cytokine storm and thus preventing pulmonary fibrosis, as they exert a strong binding affinity for viral proteins and inhibit their activity. The Health Ministry of Thailand has approved Andrographis paniculata (Jap. Senshinren) extracts to treat COVID-19. In China, over 85% of patients infected with SARS-CoV-2 receive treatments based on traditional Chinese medicine. A comprehensive map of the stages and pathogenetic mechanisms related to the disease and effective natural products to treat and prevent COVID-19 are presented. Approximately 10% of patients with COVID-19 are affected by long COVID, and COVID-19 infection impairs mitochondrial DNA. As the number of agents to treat COVID-19 is limited, adjuvant botanical drug treatments including vitamin C and E supplementation may reduce COVID-19 symptoms and inhibit progression to long COVID.}, } @article {pmid39391317, year = {2024}, author = {Kanwal, A and Zhang, Z}, title = {Exploring common pathogenic association between Epstein Barr virus infection and long-COVID by integrating RNA-Seq and molecular dynamics simulations.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1435170}, pmid = {39391317}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/virology/genetics ; *Epstein-Barr Virus Infections/genetics/virology ; *Herpesvirus 4, Human/physiology/genetics ; *Molecular Dynamics Simulation ; *RNA-Seq ; *SARS-CoV-2/physiology/genetics ; *Protein Interaction Maps ; Molecular Docking Simulation ; Leukocytes, Mononuclear/metabolism/virology ; }, abstract = {The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein-Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors. We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein-Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method. Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of -8.3 kcal/mol) with the lowest total binding energy of -18.48 kcal/mol. In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation.}, } @article {pmid39390854, year = {2024}, author = {Shah, M and Kakar, A and Gogia, A and Byotra, S and Taneja, V}, title = {Persistence of Coronavirus Disease 2019 Symptoms in Postacute Phase: Does Age, Sex, Comorbidities, and Severity of Infection Have an Impact?.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {10}, pages = {19-23}, doi = {10.59556/japi.72.0576}, pmid = {39390854}, issn = {0004-5772}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; *Comorbidity ; Middle Aged ; *Severity of Illness Index ; Prospective Studies ; India/epidemiology ; Adult ; Age Factors ; Risk Factors ; Sex Factors ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Young Adult ; }, abstract = {BACKGROUND AND OBJECTIVE: Post-coronavirus disease (COVID) persistence of symptoms and the development of complications have become frequently encountered clinical problems due to multiple waves of the pandemic over the past 3 years across the world. Identifying risk factors would enable us to direct our limited resources toward the subgroups requiring long-term follow-up and treatment. With this prospective observational study, we aim to establish a statistical correlation between the persistence of symptoms and four of the most attributed risk factors for prolonged recovery: severity of acute illness, elderly age, presence of multiple comorbidities, and female gender in the Indian population.

MATERIALS AND METHODS: Three hundred patients with positive COVID reverse transcription polymerase chain reaction (RTPCR) or antigen tests were enrolled over 10 months (from December 2020, after obtaining ethical clearance, to October 2021). Symptoms were recorded at baseline and followed up with a predesigned questionnaire to assess their persistence at 1-, 2-, and 4-month intervals post-COVID recovery. Appropriate statistical analysis [Pearson's correlation/analysis of variance (ANOVA) test] was used to establish the correlation between the persistence of symptoms and their severity with the presence of risk factors.

RESULTS: Severity of acute illness was the single most important determining factor of persistence of symptoms as well as their severity in our study (p < 0.001) at each follow-up interval. The correlation observed between average number or severity of persistent symptoms increased with female gender, increasing age-group and presence of multiple comorbidities was not significant statistically (p > 0.05) with exception of persistent fatigue in females at 2-month interval.

INTERPRETATION AND CONCLUSION: Persistent symptoms and its prevalence recorded so far represents tip of the iceberg of patients suffering with long COVID. Patients with history of severe acute illness should be followed up closely for prompt identification and rehabilitation of these cases as it had maximum bearing on the outcome of these patients.}, } @article {pmid39390853, year = {2024}, author = {Mittal, K and Khedar, RS and Gupta, R and Bharati, S and Sharma, KK and Gupta, JB and Mathur, A}, title = {Incidence of Long COVID-19 at 12-18 Months Following Delta Wave of Coronavirus Disease 2019: Hospital-based Prospective Registry.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {10}, pages = {13-18}, doi = {10.59556/japi.72.0609}, pmid = {39390853}, issn = {0004-5772}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Incidence ; Prospective Studies ; Middle Aged ; India/epidemiology ; *Registries ; Hospitalization/statistics & numerical data ; Adult ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {BACKGROUND AND OBJECTIVE: Long coronavirus disease 2019 (COVID-19) has emerged as an important consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify its incidence 12-18 months following hospitalization in patients with COVID-19, we performed a prospective study.

METHODS: Virologically confirmed successive patients with moderate-to-severe COVID-19, hospitalized during the delta wave in India, were recruited. Data on clinical features, investigations, and outcomes were obtained. Long COVID-19 was diagnosed using the European quality of life questionnaire (EQ-5D) and Birmingham symptom burden questionnaire (SBQ) at 12-18-month follow-up.

RESULTS: During the study period (January-July 2021), we evaluated 8,680 suspected COVID-19 patients, of whom 1,641 were confirmed virologically and 388 were hospitalized. Men accounted for 64.4%, individuals aged >60 years for 41.5%, hypertension for 42.8%, diabetes for 38.4%, and cardiovascular disease for 17.3%. At admission, there was a high prevalence of cough (71.1%), fever (86.6%), and oxygen requirement (38.6%). Proning was deployed in 89.2% of cases, nasal cannula in 36.3%, nonrebreather masks in 15.7%, noninvasive ventilation in 14.4%, and invasive ventilation in 16.2%. In-hospital deaths totaled 75 (19.3%), with 310 discharged for home care and eligible for follow-up. At a median follow-up of 15 months, 9 patients had died, 40 were lost to follow-up, and 264 were evaluated. The incidence of Long COVID-19 was 45 [17.0%, 95% confidence of interval (CI) 12.6-21.9%]. The median EQ-5D score was 5.0, with >5 observed in only 11 patients (0.6%). Using the SBQ, new-onset dyspnea on exertion was noted in 13 (4.9%), rest dyspnea in 7 (2.6%), fatigue in 31 (11.7%), feverishness in 18 (6.8%), and low energy in 16 (6.1%). Long COVID-19 was significantly more prevalent in women and older individuals. In Long COVID-19 compared to controls, the mean duration of oxygen requirement (5.46 ± 9.8 vs 2.46 ± 4.5 days, p = 0.002), use of nonrebreather masks (17.8 vs 7.3%, p = 0.026), noninvasive ventilation (11.1 vs 3.2%, p = 0.020), and duration of intensive care unit (ICU) stay (13.5, 8.7-17.3 vs 8.0, 5.0-11.0 days, p = 0.028) were significantly higher.

CONCLUSION: The incidence of Long COVID-19 at 12-18 months follow-up is 17.0%. It is significantly higher in women, older age groups, and patients requiring longer oxygenation, nonrebreather oxygen masks, noninvasive respiratory support, and extended stays in the ICU.}, } @article {pmid39389403, year = {2024}, author = {Montes-Ibarra, M and Godziuk, K and Thompson, RB and Chan, CB and Pituskin, E and Gross, DP and Lam, G and Schlögl, M and Felipe Mota, J and Ian Paterson, D and Prado, CM}, title = {Protocol for a pilot study: Feasibility of a web-based platform to improve nutrition, mindfulness, and physical function in people living with Post COVID-19 condition (BLEND).}, journal = {Methods (San Diego, Calif.)}, volume = {231}, number = {}, pages = {186-194}, doi = {10.1016/j.ymeth.2024.10.004}, pmid = {39389403}, issn = {1095-9130}, mesh = {Humans ; Male ; *COVID-19/psychology/therapy ; *Feasibility Studies ; Internet ; Internet-Based Intervention ; *Mindfulness/methods ; Nutritional Status ; Pilot Projects ; *Quality of Life ; SARS-CoV-2 ; Telemedicine ; Randomized Controlled Trials as Topic ; }, abstract = {Individuals with Post COVID-19 condition (PCC), or long COVID, experience symptoms such as fatigue, muscle weakness, and psychological distress, including anxiety, depression, or sleep disorders that persist after recovery from COVID-19. These ongoing symptoms significantly compromise quality of life and diminish functional capacity and independence. Multimodal digital interventions targeting behavioural factors such as nutrition and mindfulness have shown promise in improving health outcomes of people with chronic health conditions and may be beneficial for those with PCC. The BLEND study (weB-based pLatform to improve nutrition, mindfulnEss, and physical function, in patients with loNg COVID) study is an 8-week pilot randomized controlled trial evaluating the feasibility of a digital wellness platform compared to usual care among individuals with PCC. The web-based wellness platform employed in this study, My Viva Plan (MVP)®, integrates a holistic, multicomponent approach to promote wellness. The intervention group receives access to the digital health platform for 8 weeks with encouragement for frequent interactions to improve dietary intake and mindfulness. The control group receives general content focusing on improvements in dietary intake and mindfulness. Assessments are conducted at baseline and week 8. The primary outcome is the feasibility of platform use. Secondary and exploratory outcomes include a between-group comparison of changes in body composition, nutritional status, quality of life, mindfulness, physical activity, and physical performance after 8 weeks. Findings of this study will inform the development of effective web-based wellness programs tailored for individuals with PCC to promote sustainable behavioural changes and improved health outcomes.}, } @article {pmid39389388, year = {2025}, author = {Morse, BA and Motovilov, K and Michael Brode, W and Michael Tee, F and Melamed, E}, title = {A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {725-738}, doi = {10.1016/j.bbi.2024.10.006}, pmid = {39389388}, issn = {1090-2139}, mesh = {Humans ; *Immunoglobulins, Intravenous/therapeutic use/administration & dosage ; *COVID-19/immunology/complications/therapy ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Guillain-Barre Syndrome/therapy/immunology/drug therapy ; }, abstract = {Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation. In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients. This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.}, } @article {pmid39388619, year = {2024}, author = {Neuman, N and Lövestam, E and Karlén, J and Sandvik, P}, title = {Sensing Sociality: Disruptions of Social Life When Living With Chemosensory Dysfunctions After COVID-19.}, journal = {Qualitative health research}, volume = {}, number = {}, pages = {10497323241278551}, doi = {10.1177/10497323241278551}, pmid = {39388619}, issn = {1049-7323}, abstract = {Taste and smell are of direct importance in most social interactions. Radical disruptions in these senses can, therefore, substantially disrupt sociality. This paper focuses on the experiences of a particular type of disruption: persistent chemosensory dysfunctions after COVID-19. We conducted semi-structured interviews with 30 patients undergoing treatment for chemosensory dysfunctions and analyzed the ways in which their experiences have influenced social relations and activities, particularly regarding food and eating. The findings reveal that these dysfunctions have made the participants markedly aware that food and eating are pivotal to full participation in social life. As is smell, both surrounding smells and the perception of one's own smell, with dysfunctions leading to several social consequences. Such problems are handled through both avoidance behavior and adaptations. While adaptations facilitate interactions, they come at the cost of feeling a burden to others or not fully appreciating an event (e.g., a shared meal). Social support is of great importance, ranging from minor practical assistance, such as a friend checking if the milk is sour, to the profound emotional relief felt from empathic treatment and recognition that the problems are real. Here, healthcare professionals can play a vital role, even in the (perceived) absence of clinical effectiveness of the treatment. The experiences expressed are partially in line with other manifestations of Long COVID and with chemosensory dysfunctions due to other illnesses, but only partially, since this is a patient group with needs and experiences that are unique, in that sociality is so strongly affected solely by disruptions in sensory abilities.}, } @article {pmid39386803, year = {2024}, author = {Wu, H and Zhang, Y and Tang, W and Lv, M and Chen, Z and Meng, F and Zhao, Y and Xu, H and Dai, Y and Xue, J and Wang, J and Dong, L and Wu, D and Zhang, S and Xue, R}, title = {Liver function abnormality on admission predicts long COVID syndrome in digestive system.}, journal = {Heliyon}, volume = {10}, number = {19}, pages = {e37664}, pmid = {39386803}, issn = {2405-8440}, abstract = {BACKGROUND: Clinical practice showed that many patients with SARS-CoV-2 infection presented with long COVID syndrome in digestive system. We sought to investigate the factor affecting the incidence of long COVID syndrome in digestive system.

METHODS AND RESULTS: Patients with SARS-CoV-2 infection diagnosed at two centers of Zhongshan Hospital and one center of Shanghai Pudong Hospital from March 01, 2022 to May 31, 2022 were enrolled, collected in the hospital database, and followed up until March 30, 2023. The primary outcome of the study was the occurrence of post-acute sequelae of COVID-19 in the digestive system (long COVID syndrome). Modified Poisson regression was used to calculate the relative risk (RR). This cohort study included 494 patients with SARS-CoV-2 infection, 144 (29.1 %) patients developed liver function abnormality on admission. During the follow-up period, the primary study outcome occurred in 30 (20.8 %) of the group presenting with liver function abnormality on admission and in 20 (5.7 %) of the group without liver function abnormality on admission (adjusted, RR = 3.550, 95%CI: 2.099-6.006, P ≤ 0.001).

CONCLUSION: Our study suggests that patients with COVID-19 who experience liver function abnormality on admission have an increased risk of developing long COVID syndrome in the digestive system.}, } @article {pmid39386210, year = {2024}, author = {Elahi, S and Rezaeifar, M and Osman, M and Shahbaz, S}, title = {Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1443363}, pmid = {39386210}, issn = {1664-3224}, mesh = {Humans ; *Galectins/blood ; *Biomarkers/blood ; *Fatigue Syndrome, Chronic/blood/diagnosis/etiology ; *COVID-19/blood/complications/immunology/diagnosis ; Male ; Female ; Middle Aged ; Adult ; *Nerve Tissue Proteins/blood ; *SARS-CoV-2 ; *Inflammation/blood ; Cognition ; Antigens, Neoplasm ; Biomarkers, Tumor ; }, abstract = {This study aimed to assess plasma galectin-9 (Gal-9) and artemin (ARTN) concentrations as potential biomarkers to differentiate individuals with Long COVID (LC) patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) from SARS-CoV-2 recovered (R) and healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis determined a cut-off value of plasma Gal-9 and ARTN to differentiate LC patients from the R group and HCs in two independent cohorts. Positive correlations were observed between elevated plasma Gal-9 levels and inflammatory markers (e.g. SAA and IP-10), as well as sCD14 and I-FABP in LC patients. Gal-9 also exhibited a positive correlation with cognitive failure scores, suggesting its potential role in cognitive impairment in LC patients with ME/CFS. This study highlights plasma Gal-9 and/or ARTN as sensitive screening biomarkers for discriminating LC patients from controls. Notably, the elevation of LPS-binding protein in LC patients, as has been observed in HIV infected individuals, suggests microbial translocation. However, despite elevated Gal-9, we found a significant decline in ARTN levels in the plasma of people living with HIV (PLWH). Our study provides a novel and important role for Gal-9/ARTN in LC pathogenesis.}, } @article {pmid39385068, year = {2024}, author = {Sangkaew, S and Tumviriyakul, H and Cheranakhorn, C and Songumpai, N and Pinpathomrat, N and Seeyankem, B and Yasharad, K and Loomcharoen, P and Pakdee, W and Changawej, C and Dumrongkullachart, D and Limheng, A and Dorigatti, I}, title = {Unveiling Post-COVID-19 syndrome: incidence, biomarkers, and clinical phenotypes in a Thai population.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1132}, pmid = {39385068}, issn = {1471-2334}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; MR/X020258/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Biomarkers/blood ; Incidence ; Phenotype ; Prospective Studies ; Quality of Life ; Risk Factors ; Southeast Asian People ; Survivors/statistics & numerical data ; Thailand/epidemiology ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Post-COVID- 19 syndrome (PCS) significantly impacts the quality of life of survivors. There is, however, a lack of a standardized approach to PCS diagnosis and management. Our bidirectional cohort study aimed to estimate PCS incidence, identify risk factors and biomarkers, and classify clinical phenotypes for enhanced management to improve patient outcomes.

METHODS: A bidirectional prospective cohort study was conducted at five medical sites in Hatyai district in Songkhla Province, Thailand. Participants were randomly selected from among the survivors of COVID-19 aged≥18 years between May 15, 2022, and January 31, 2023. The selected participants underwent a scheduled outpatient visit for symptom and health assessments 12 to 16 weeks after the acute onset of infection, during which PCS was diagnosed and blood samples were collected for hematological, inflammatory, and serological tests. PCS was defined according to the World Health Organization criteria. Univariate and multiple logistic regression analyses were used to identify biomarkers associated with PCS. Moreover, three clustering methods (agglomerative hierarchical, divisive hierarchical, and K-means clustering) were applied, and internal validation metrics were used to determine clustering and similarities in phenotypes.

FINDINGS: A total of 300 survivors were enrolled in the study, 47% of whom developed PCS according to the World Health Organization (WHO) definition. In the sampled cohort, 66.3% were females, and 79.4% of them developed PCS (as compared to 54.7% of males, p-value <0.001). Comorbidities were present in 19% (57/300) of all patients, with 11% (18/159) in the group without PCS and 27.7% (39/141) in the group with PCS. The incidence of PCS varied depending on the criteria used and reached 13% when a quality of life indicator was added to the WHO definition. Common PCS symptoms were hair loss (22%) and fatigue (21%), while mental health symptoms were less frequent (insomnia 3%, depression 3%, anxiety 2%). According to our univariate analysis, we found significantly lower hematocrit and IgG levels and greater ALP levels in PCS patients than in patients who did not develop PCS (p-value < 0.05). According to our multivariable analysis, adjusted ALP levels remained a significant predictor of PCS (OR 1.02, p-value= 0.005). Clustering analysis revealed four groups characterized by severe clinical symptoms and mental health concerns (Cluster 1, 4%), moderate physical symptoms with predominant mental health issues (Cluster 2, 9%), moderate mental health issues with predominant physical symptoms (Cluster 3, 14%), and mild to no PCS (Cluster 4, 77%). The quality of life and ALP levels varied across the clusters.

INTERPRETATION: This study challenges the prevailing diagnostic criteria for PCS, emphasizing the need for a holistic approach that considers quality of life. The identification of ALP as a biomarker associated with PCS suggests that its monitoring could be used for early detection of the onset of PCS. Cluster analysis revealed four distinct clinical phenotypes characterized by different clinical symptoms and mental health concerns that 'exhibited varying impacts on quality of life. This finding suggested that accounting for the reduced quality of life in the definition of PCS could enhance its diagnosis and management and that moving toward personalized interventions could both improve patient outcomes and help reduce medicalization and optimally target the available resources.

FUNDING: The research publication received funding support from Medical Council of Thailand (Police General Dr. Jongjate Aojanepong Foundation), Hatyai Hospital Charity and Wellcome Trust.}, } @article {pmid39384321, year = {2024}, author = {Hawke, LD and Nguyen, ATP and Wang, W and Brown, EE and Xu, D and Deuville, S and Goulding, S and Ski, CF and Rossell, SL and Thompson, DR and Rodak, T and Strudwick, G and Castle, D}, title = {Systematic review of interventions for mental health, cognition and psychological well-being in long COVID.}, journal = {BMJ mental health}, volume = {27}, number = {1}, pages = {}, pmid = {39384321}, issn = {2755-9734}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Mental Health ; *Cognition ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Psychosocial Intervention/methods ; Psychological Well-Being ; }, abstract = {AIMS: This systematic review aims to identify and synthesise the publicly available research testing treatments for mental health, cognition and psychological well-being in long COVID.

METHODS: The following databases and repositories were searched in October-November 2023: Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Internet, WANFANG Data, Web of Science's Preprint Citation Index, The Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Articles were selected if they described participants with long COVID symptoms at least 4 weeks after SAR-CoV-19 infection, reported primary outcomes on mental health, cognition and/or psychological well-being, and were available with at least an English-language summary. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews were followed.

RESULTS: Thirty-three documents representing 31 studies were included. Seven tested psychosocial interventions, five pharmaceutical interventions, three natural supplement interventions, nine neurocognitive interventions, two physical rehabilitation interventions and five integrated interventions. While some promising findings emerged from randomised controlled trials, many studies were uncontrolled; a high risk of bias and insufficient reporting were also frequent.

CONCLUSIONS: The published literature on treatments for mental health, cognition and psychological well-being in long COVID show that the interventions are highly heterogeneous and findings are inconclusive to date. Continued scientific effort is required to improve the evidence base. Regular literature syntheses will be required to update and educate clinicians, scientists, interventionists and the long COVID community.}, } @article {pmid39382809, year = {2024}, author = {Costa, D and Grandolfo, S and Birreci, D and Angelini, L and Passaretti, M and Cannavacciuolo, A and Martini, A and De Riggi, M and Paparella, G and Fasano, A and Bologna, M}, title = {Impact of SARS-CoV-2 Infection on Essential Tremor: A Retrospective Clinical and Kinematic Analysis.}, journal = {Cerebellum (London, England)}, volume = {23}, number = {6}, pages = {2477-2486}, pmid = {39382809}, issn = {1473-4230}, mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Female ; Male ; *Essential Tremor/physiopathology/epidemiology ; Retrospective Studies ; Aged ; Biomechanical Phenomena ; Middle Aged ; Aged, 80 and over ; Accelerometry ; SARS-CoV-2 ; }, abstract = {In the past few years, SARS-CoV-2 infection has substantially impacted public health. Alongside respiratory symptoms, some individuals have reported new neurological manifestations or a worsening of pre-existing neurological conditions. We previously documented two cases of essential tremor (ET) who experienced a deterioration in tremor following SARS-CoV-2 infection. However, the effects of SARS-CoV-2 on ET remain largely unexplored. This study aims to evaluate the impact of SARS-CoV-2 infection on a relatively broad sample of ET patients by retrospectively comparing their clinical and kinematic data collected before and after the exposure to SARS-CoV-2. We surveyed to evaluate the impact of SARS-CoV-2 infection on tremor features in ET. Subsequently, we retrospectively analysed clinical and kinematic data, including accelerometric recordings of postural and kinetic tremor. We included 36 ET patients (14 females with a mean age of 71.1 ± 10.6 years). Among the 25 patients who reported SARS-CoV-2 infection, 11 (44%) noted a subjective worsening of tremor. All patients reporting subjective tremor worsening also exhibited symptoms of long COVID, whereas the prevalence of these symptoms was lower (50%) in those without subjective exacerbation. The retrospective analysis of clinical data revealed a tremor deterioration in infected patients, which was not observed in non-infected patients. Finally, kinematic analysis revealed substantial stability of tremor features in both groups. The study highlighted a potential correlation between the SARS-CoV-2 infection and clinical worsening of ET. Long COVID contributes to a greater impact of tremor on the daily life of ET patients.}, } @article {pmid39382736, year = {2024}, author = {Huynh, DTN and Nguyen, HT and Hsieh, CM}, title = {Taiwan Chingguan Yihau may improve post-COVID-19 respiratory complications through PI3K/AKT, HIF-1, and TNF signaling pathways revealed by network pharmacology analysis.}, journal = {Molecular diversity}, volume = {}, number = {}, pages = {}, pmid = {39382736}, issn = {1573-501X}, abstract = {The emergence of new SARS-CoV-2 variants with a higher contagious capability and faster transmissible speed has imposed an incessant menace on global health and the economy. The SARS-CoV-2 infection might reoccur and last much longer than expected. Thence, there is a high possibility that COVID-19 can cause long-term health problems. This condition needs to be investigated thoroughly, especially the post-COVID-19 complications. Respiratory tract disorders are common and typical complications after recovery. Until now, there has been a lack of data on specialized therapeutic medicine for post-COVID-19 complications. The clinical efficacy of NRICM101 has been demonstrated in hospitalized COVID-19 patients. This herbal medicine may also be a promising therapy for post-COVID-19 complications, thanks to its phytochemical constituents. The potential pharmacological mechanisms of NRICM101 in treating post-COVID-19 respiratory complications were investigated using network pharmacology combined with molecular docking, and the results revealed that NRICM101 may exert a beneficial effect through the three primary pathways: PI3K/AKT, HIF-1, and TNF signaling pathways. Flavonoids (especially quercetin) have a predominant role and synergize with other active compounds to produce therapeutic effectiveness. Most of the main active compounds exist in three chief herbal ingredients, including Liquorice root (Glycyrrhiza glabra), Scutellaria root (Scutellaria baicalensis), and Mulberry leaf (Morus alba). To our knowledge, this is the first study of the NRICM101 effect on post-COVID-19 respiratory complications. Our findings may provide a better understanding of the potential mechanisms of NRICM101 in treating SARS-CoV-2 infection and regulating the immunoinflammatory response to improve post-COVID-19 respiratory complications.}, } @article {pmid39382470, year = {2024}, author = {Sharma, SK and Mohan, A and Upadhyay, V}, title = {Long COVID syndrome: An unfolding enigma.}, journal = {The Indian journal of medical research}, volume = {159}, number = {6}, pages = {585-600}, pmid = {39382470}, issn = {0971-5916}, mesh = {Humans ; *COVID-19/epidemiology/complications/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Risk Factors ; }, abstract = {Post-acute sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19), called as long COVID syndrome, is a major global public health issue after recovery from COVID-19. The disease occurs in symptomatic patients irrespective of illness severity. The symptoms continue after four wk of recovery from acute illness and persist beyond three months. Risk factors for long COVID include older age, female gender, multiple co-morbidities including diabetes mellitus, prior chronic respiratory illnesses, hospitalized patients with severe disease, especially receiving assisted ventilation, high viral load, reactivation of Epstein Barr (EB) virus and human herpes virus 6 (HH6), circulating auto antibodies against various organs and type I interferon. The prevalence varies from 10 to 20 per cent, and most data have been reported from high-income countries. Any system can get involved in long COVID. The symptoms include fatigue, cognition impairment, cough and dyspnoea, anosmia, hair loss and diarrhoea, among others. While there are no laboratory tests for confirmation of diagnosis, reduced complement C7 complexes at six months, and a two-gene biomarker including FYN and SARS-CoV-2 antisense ribonucleic acid (RNA) are emerging as potentially useful biomarkers for long COVID. There should be no alternative disease to explain various symptoms. Vaccination against SARS-CoV-2 and early use of oral antiviral nirmatrelvir within the first five days in patients with acute mild disease having various risk factors for progression to severe disease help in preventing long COVID. Several clinical trials are underway for the treatment of long COVID and the results of these are eagerly awaited. Physical and mental rehabilitation at home, at community level or in the hospital setting as appropriate is essential in patients with long COVID.}, } @article {pmid39381546, year = {2024}, author = {Greenwood, DC and Mansoubi, M and Bakerly, ND and Bhatia, A and Collett, J and Davies, HE and Dawes, J and Delaney, B and Ezekiel, L and Leveridge, P and Mir, G and Muhlhausen, W and Rayner, C and Read, F and Scott, JT and Sivan, M and Tucker-Bell, I and Vashisht, H and Ward, T and O'Connor, DB and Dawes, H and , }, title = {Physical, cognitive, and social triggers of symptom fluctuations in people living with long COVID: an intensive longitudinal cohort study.}, journal = {The Lancet regional health. Europe}, volume = {46}, number = {}, pages = {101082}, pmid = {39381546}, issn = {2666-7762}, abstract = {BACKGROUND: Symptom fluctuations within and between individuals with long COVID are widely reported, but the extent to which severity varies following different types of activity and levels of exertion, and the timing of symptoms and recovery, have not previously been quantified. We aimed to characterise timing, severity, and nature of symptom fluctuations in response to effortful physical, social and cognitive activities, using Ecological Momentary Assessments.

METHODS: We recorded activity, effort, and severity of 8 core symptoms every 3 h for up to 24 days, in cohorts from both clinic and community settings. Symptom severities were jointly modelled using autoregressive and moving average processes.

FINDINGS: Consent was received from 376 participants providing ≥1 week's measurements (273 clinic-based, 103 community-based). Severity of all symptoms was elevated 30 min after all categories of activity. Increased effort was associated with increased symptom severity. Fatigue severity scores increased by 1.8/10 (95% CI: 1.6-1.9) following the highest physical exertions and by 1.5 (1.4-1.7) following cognitive efforts. There was evidence of only mild delayed fatigue 3 h (0.3, 0.2-0.5) or one day later (0.2, 0.0- 0.5). Fatigue severity increased as the day progressed (1.4, 1.0-1.7), and cognitive dysfunction was 0.2 lower at weekends (0.1-0.3).

INTERPRETATION: Cognitive, social, self-care and physical activities all triggered increased severity across every symptom, consistent with associated common pathways as potential therapeutic targets. Clear patterns of symptom fluctuations emerged that support more targeted self-management.

FUNDING: National Institute for Health and Care Research.}, } @article {pmid39381125, year = {2024}, author = {Eslami, Z and Joshaghani, H}, title = {Investigating the Role of Serotonin Levels in Cognitive Impairments Associated with Long COVID-19.}, journal = {Chonnam medical journal}, volume = {60}, number = {3}, pages = {141-146}, pmid = {39381125}, issn = {2233-7385}, abstract = {This study aimed to investigate the activation of the inflammation process, triggered as an immune response to combat the invasion by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named 'coronavirus disease 2019' (COVID-19). Several mechanisms contribute to the reduction in serotonin levels, such as the impaired absorption of dietary tryptophan, hindered serotonin transport via platelets, and increased activity of an enzyme responsible for breaking down serotonin. Individuals seeking treatment for long COVID-19 had lower serotonin levels in their blood than those who had fully recovered from the infection. Furthermore, patients with long COVID-19 also had reduced tryptophan levels. The potential benefits of dietary supplementation with tryptophan or the use of selective serotonin reuptake inhibitors (SSRIs) to improve cognitive impairments and depressive and anxiety disorders in long-term COVID-19 patients. The findings support the immune response's pivotal role in modulating serotonin levels and further highlight the intricate connection between the immune system and neurotransmitter regulation.}, } @article {pmid39380657, year = {2024}, author = {Delpino, MV and Quarleri, J}, title = {Aging mitochondria in the context of SARS-CoV-2: exploring interactions and implications.}, journal = {Frontiers in aging}, volume = {5}, number = {}, pages = {1442323}, pmid = {39380657}, issn = {2673-6217}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented global challenges with a diverse clinical spectrum, including severe respiratory complications and systemic effects. This review explores the intricate relationship between mitochondrial dysfunction, aging, and obesity in COVID-19. Mitochondria are vital for cellular energy provision and resilience against age-related macromolecule damage accumulation. They manage energy allocation in cells, activating adaptive responses and stress signals such as redox imbalance and innate immunity activation. As organisms age, mitochondrial function diminishes. Aging and obesity, linked to mitochondrial dysfunction, compromise the antiviral response, affecting the release of interferons, and worsening COVID-19 severity. Furthermore, the development of post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID has been associated with altered energy metabolism, and chronic immune dysregulation derived from mitochondrial dysfunction. Understanding the interplay between mitochondria, aging, obesity, and viral infections provides insights into COVID-19 pathogenesis. Targeting mitochondrial health may offer potential therapeutic strategies to mitigate severe outcomes and address long-term consequences in infected individuals.}, } @article {pmid39380062, year = {2024}, author = {Butzin-Dozier, Z and Ji, Y and Deshpande, S and Hurwitz, E and Anzalone, AJ and Coyle, J and Shi, J and Mertens, A and van der Laan, MJ and Colford, JM and Patel, RC and Hubbard, AE and , }, title = {SSRI use during acute COVID-19 and risk of long COVID among patients with depression.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {445}, pmid = {39380062}, issn = {1741-7015}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Selective Serotonin Reuptake Inhibitors/therapeutic use ; Female ; Male ; Middle Aged ; *SARS-CoV-2/drug effects ; Adult ; Aged ; Depression/drug therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; Coronavirus Infections/drug therapy/epidemiology/complications ; Betacoronavirus/drug effects ; Pneumonia, Viral/drug therapy/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.

METHODS: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.

RESULTS: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).

CONCLUSIONS: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.}, } @article {pmid39379918, year = {2024}, author = {Garbsch, R and Schäfer, H and Kotewitsch, M and Mooren, JM and Waranski, M and Teschler, M and Vereckei, K and Böll, G and Mooren, FC and Schmitz, B}, title = {Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {446}, pmid = {39379918}, issn = {1741-7015}, mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/rehabilitation/physiopathology/complications ; Prospective Studies ; Adult ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Exercise Therapy/methods ; Sex Factors ; Cardiorespiratory Fitness/physiology ; SARS-CoV-2 ; Fatigue/rehabilitation/physiopathology ; Respiratory Function Tests ; Exercise Test/methods ; }, abstract = {BACKGROUND: Post-COVID-19 Syndrome (PCS) entails a spectrum of symptoms, including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. Given the effectiveness of exercise-based rehabilitation for PCS, this study examined the efficacy of rehabilitation for PCS patients, focusing on sex-specific differences.

METHODS: Prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and spirometry were performed at admission and discharge. Questionnaires were used to assess fatigue, health-related quality of life, wellbeing, and workability for up to 6 months.

RESULTS: 145 patients (36% female, 47.1 ± 12.7 years; 64% male, 52.0 ± 9.1 years; p = 0.018) were referred to rehabilitation 262.0 ± 128.8 days after infection (female, 285.5 ± 140.6 days; male, 248.8 ± 112.0 days; p = 0.110). Lead symptoms included fatigue/exercise intolerance (81.4%), shortness of breath (74.5%), and cognitive dysfunction (52.4%). Women presented with higher relative baseline exercise capacity (82.0 ± 14.3%) than males (68.8 ± 13.3%, p < 0.001), but showed greater improvement in submaximal workload (p = 0.026). Men exhibited higher values for FEV1, FEV1/VC, PEF, and MEF and lower VC at baseline (p ≤ 0.038), while FEV1/VC improvement more in women (p = 0.027). Higher baseline fatigue and lower wellbeing was detected in women and correlated with impaired pulmonary function (p < 0.05). Disease perception including fatigue, health-related quality of life, wellbeing and workability improved with rehabilitation for up to six-month.

CONCLUSIONS: Rehabilitation improves cardiopulmonary fitness, pulmonary function and disease burden in women and men with long-term PCS. Women with PCS may benefit from intensified respiratory muscle training. Clinical assessment should include cardiopulmonary exercise testing and pulmonary function tests and fatigue assessments for all PCS patients to document limitations and tailor therapeutical strategies.}, } @article {pmid39379779, year = {2024}, author = {MacEwan, SR and Rahurkar, S and Tarver, WL and Eiterman, LP and Melnyk, H and Olvera, RG and Eramo, JL and Teuschler, L and Gaughan, AA and Rush, LJ and Stanwick, S and Burpee, SB and McConnell, E and Schamess, A and McAlearney, AS}, title = {The Impact of Long COVID on Employment and Well-Being: A Qualitative Study of Patient Perspectives.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {39379779}, issn = {1525-1497}, support = {U54 CA260582/CA/NCI NIH HHS/United States ; U54CA260582/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Exploring the experiences of Long COVID patients who face challenges with employment may inform improvements in how healthcare systems can provide holistic care for this patient population.

OBJECTIVE: Understand perspectives about the impact of Long COVID on employment and well-being among patients seeking healthcare for Long COVID.

DESIGN: Qualitative study involving one-on-one interviews.

PARTICIPANTS: Eligible participants were 18 years of age or older, spoke English, self-reported as doing well in daily life before having COVID-19, and reported that COVID-19 was still having a significant impact on their life three or more months following an acute infection.

APPROACH: Participants were recruited from a post-COVID recovery clinic at an academic medical center. Interviews were conducted from August to September 2022.

KEY RESULTS: Among all participants (N = 21), most described that they were not able to work at a capacity equivalent to their norm pre-COVID-19. For those who continued working after their COVID-19 infection, the effort and energy required for work left little capacity to participate in other life activities and made it difficult to attend recommended healthcare appointments. Participants reported financial impacts of changes in employment including loss of income and changes in insurance, which were compounded by high healthcare costs. Changes in employment resulted in emotional repercussions including feelings of loss of self-identity and fear of judgement at work. Participants discussed issues surrounding access to strategies to address challenges posed by the impact of Long COVID on employment, including strategies learned from healthcare providers to cope with Long COVID symptoms at work and efforts to seek disability benefits or workplace accommodations.

CONCLUSIONS: Patients with Long COVID may face significant challenges due to changes in their ability to work. Healthcare providers can support these patients by connecting them to financial assistance resources, facilitating appropriate mental health treatment, and expediting workplace accommodation requests.}, } @article {pmid39379681, year = {2024}, author = {Rutjanawech, S and Sritipsukho, P and Sritipsukho, S}, title = {Long COVID at 3 and 6 months after covid-19 infection in Thailand.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {23441}, pmid = {39379681}, issn = {2045-2322}, support = {65-050//Health Systems Research Institute, Thailand/ ; 65-050//Health Systems Research Institute, Thailand/ ; 65-050//Health Systems Research Institute, Thailand/ ; }, mesh = {Humans ; Thailand/epidemiology ; *COVID-19/epidemiology/virology ; Female ; Male ; Middle Aged ; Adult ; *SARS-CoV-2/isolation & purification ; Prevalence ; Risk Factors ; Aged ; Post-Acute COVID-19 Syndrome ; Time Factors ; }, abstract = {"Long COVID", which describes a diverse set of symptoms or conditions that persist or develop after four weeks from the onset of initial SARS-CoV-2 infection has been introduced. However, the true prevalence varies worldwide. This study aimed to determine the point prevalence and clinical characteristics of long COVID at three and six months after acute COVID-19 infection in Thailand. Methods All adult patients who were diagnosed with COVID-19 by positive nasopharyngeal RT-PCR for SARS-CoV-2 at Thammasat University Hospital between October and December 2021 were recruited and followed for long COVID symptoms by telephone interviews at 3 and 6 months after an acute infection. Among 1,400 eligible COVID-19 cases, interviews were complete for 1,129 and 932 individuals at 3 and 6 months, respectively. Of those, 431 and 314 reported at least one symptom consistent with long COVID. The point prevalence was 38.2% (95% confidence interval: 35.3-41.1%) and 33.7% (95% confidence interval: 30.7-36.7%) respectively. Female gender, disease severity, and symptomatic acute infection were identified as independent risk factors. Conclusion Based on the reported symptoms, long COVID is commonly observed either at 3 or 6 months in our study.}, } @article {pmid39377521, year = {2025}, author = {Mohammadifard, N and Arefian, M and Najafian, J and Shahsanaei, A and Javanbakht, S and Mahmoudi, S and Nouri, F and Sayyah, M and Nilforoushzadeh, F and Ahmadian, M and Haghighatdoost, F and Sarrafzadegan, N}, title = {Association of obesity status and the risk of long-COVID: Isfahan COVID cohort study.}, journal = {Clinical obesity}, volume = {15}, number = {1}, pages = {e12708}, doi = {10.1111/cob.12708}, pmid = {39377521}, issn = {1758-8111}, support = {199093//Isfahan University of Medical Sciences/ ; }, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology/complications ; *Body Mass Index ; Middle Aged ; *Obesity/complications/epidemiology ; Adult ; *SARS-CoV-2 ; Risk Factors ; *Waist Circumference ; Iran/epidemiology ; Cohort Studies ; Obesity, Abdominal/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {People with COVID-19 infection continue to have their symptoms or develop new ones after recovery. This is called long-COVID syndrome. We aimed to examine the association of general and abdominal obesity with long COVID. This study was conducted using Isfahan COVID Cohort (ICC). Totally 4008 including 3213 hospitalized and 795 non-hospitalized patients with positive RT-PCR were included. Body mass index (BMI) and waist circumference (WC) were calculated. BMI >25 kg/m[2] and WC >88 cm in women and 102 cm in men were considered generally and abdominally obese, respectively. By using an open-ended questionnaire, subjects were asked whether they had any new or persistent symptom. Reported symptoms were categorized in three different fields including general, cardiac, and respiratory symptoms. Higher BMI and WC tended to increase general symptoms (odds ratio [OR] for BMI = 1.16, 95 % confidence interval (95% CI): 0.97, 1.38, and OR for WC = 1.14, 95% CI: 0.99, 1.32). Higher BMI significantly increased cardiovascular (OR = 1.38, 95% CI: 1.14, 1.67) and respiratory symptoms (OR = 1.43, 95% CI: 1.15, 1.78). Compared with patients with normal WC, the risk of cardiovascular (OR = 1.44, 95% CI: 1.24, 1.69) and respiratory symptoms was significantly higher in subjects with abdominal obesity (OR = 1.31, 95% CI: 1.10, 1.56). We found that general and abdominal obesity were associated with increased risk of cardiovascular and respiratory symptoms in patients with long-COVID symptoms. However, only general obesity was associated with increased risk of general symptoms.}, } @article {pmid39376493, year = {2024}, author = {Fernández-de-Las-Peñas, C and Arendt-Nielsen, L}, title = {Editorial: Updating long COVID: mechanisms, risk factors, and treatment.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1490242}, pmid = {39376493}, issn = {1662-5161}, } @article {pmid39374820, year = {2025}, author = {Edgell, H and Pereira, TJ and Kerr, K and Bray, R and Tabassum, F and Sergio, L and Badhwar, S}, title = {Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: A pilot study.}, journal = {Respiratory physiology & neurobiology}, volume = {331}, number = {}, pages = {104360}, doi = {10.1016/j.resp.2024.104360}, pmid = {39374820}, issn = {1878-1519}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Autonomic Nervous System/physiopathology ; *Breathing Exercises/methods ; *COVID-19/complications/physiopathology ; *Fatigue Syndrome, Chronic/physiopathology/rehabilitation/therapy ; Heart Rate/physiology ; Pilot Projects ; *Post-Acute COVID-19 Syndrome ; *Respiratory Muscles/physiopathology ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are debilitating post-viral conditions with many symptomatic overlaps, including exercise intolerance and autonomic dysfunction. Both conditions are growing in prevalence, and effective safe treatment strategies must be investigated. We hypothesized that inspiratory muscle training (IMT) could be used in PASC and mild to moderate ME/CFS to mitigate symptoms, improve exercise capacity, and improve autonomic function. We recruited healthy controls (n=12; 10 women), people with PASC (n=9; 8 women), and people with mild to moderate ME/CFS (n=12; 10 women) to complete 8 weeks of IMT. This project was registered as a clinical trial (NCT05196529) with clinicaltrials.gov. After completion of IMT, all groups experienced improvements in inspiratory muscle pressure (p<0.001), 6-minute walk distance (p=0.002), resting heart rate (p=0.037), heart rate variability (p<0.05), and symptoms related to sleep (p=0.009). In the ME/CFS group only, after completion of IMT, there were additional improvements with regard to vascular function (p=0.001), secretomotor function (p=0.023), the total weighted score (p=0.005) of the COMPASS 31 autonomic questionnaire, and symptoms related to pain (p=0.016). We found that after 8 weeks of IMT, people with PASC and/or ME/CFS could see some overall improvements in their autonomic function and symptomology.}, } @article {pmid39374592, year = {2024}, author = {D'Souza, AN and Granger, CL and Calulo Rivera, Z and Burke, A and Ngwenya, R and Struck, C and Merrett, M and Fazio, TN and Juj, G and Peiris, CL}, title = {Feasibility of an allied health led, workplace delivered Long COVID service for hospital staff: a mixed-methods study.}, journal = {Australian health review : a publication of the Australian Hospital Association}, volume = {48}, number = {6}, pages = {729-738}, doi = {10.1071/AH24146}, pmid = {39374592}, issn = {1449-8944}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Female ; Male ; Middle Aged ; *Feasibility Studies ; Adult ; SARS-CoV-2 ; Personnel, Hospital/psychology ; Surveys and Questionnaires ; Workplace ; Allied Health Personnel/psychology ; Interviews as Topic ; }, abstract = {Objective This study aimed to evaluate the feasibility of a workplace-delivered outpatient multidisciplinary service (ReCOV) for staff experiencing post COVID-19 condition ('Long COVID'). Methods A mixed-methods study of staff at a large, tertiary hospital with Long COVID who attended the service was conducted. Participants completed questionnaires to determine baseline symptoms and were offered allied health appointments for up to 12weeks each based on clinical indication. Acceptability, implementation, practicality and limited efficacy were evaluated via one-on-one semi-structured interviews and analysed using inductive thematic analysis. Limited efficacy was evaluated via pre- and post-questionnaires and demand via multidisciplinary utilisation. Results Twenty-three (median age 37 [interquartile range 30-45] years, 52% female) participants were included. Participants had appointments with a median of 4 [3-5] different professions; most commonly exercise physiology (n =19, 83%), occupational therapy (n =17, 74%) and neuropsychology (n =15, 65%). Median time spent on the ReCOV service was 15 [9-19] weeks. Thirteen semi-structured interviews were completed and analysed. Participants valued ReCOV for being a COVID-19 specific, convenient, flexible and multidisciplinary service at their workplace. Participants preferred the service to have been available for longer than 12weeks to achieve further benefits as many participants perceived little change in physical health. Conclusions Attending a multidisciplinary service located at their workplace was feasible for staff to manage post COVID-19 symptoms. Further research is required to confirm the efficacy on patient outcomes.}, } @article {pmid39374300, year = {2024}, author = {Sepúlveda, N and Malato, J and Winck, JC and Vaz Carneiro, A and Serra Hoffman, J and Branco, J}, title = {Post-Infection Fatigue Syndromes in the Era of Long COVID: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Acta medica portuguesa}, volume = {37}, number = {12}, pages = {819-822}, doi = {10.20344/amp.21845}, pmid = {39374300}, issn = {1646-0758}, } @article {pmid39372835, year = {2024}, author = {Sakai, K and Tarutani, S and Okamura, T and Yoneda, H and Kawasaki, T and Takeda, M}, title = {Comparing personality traits of healthcare workers with and without long COVID: Cross-sectional study.}, journal = {PCN reports : psychiatry and clinical neurosciences}, volume = {3}, number = {4}, pages = {e70017}, pmid = {39372835}, issn = {2769-2558}, abstract = {AIM: Pathological mechanisms of "long COVID" after recovery from the main symptoms of COVID-19 are unclear. We compared psychological differences between individuals with and without long COVID symptoms after initial COVID-19 infections.

METHODS: This study includes medical workers with and without history of COVID-19. We assessed the degree of depression, health-related quality of life (HRQOL), the degree of anxiety and fear of COVID-19, and we used an original questionnaire. In the COVID-19 group, we also assessed personality traits and anxiety. The COVID-19 group was subclassified into those with and without long COVID to examine differences in circumstantial and psychological examinations.

RESULTS: Of 310 participants (141 men, 169 women, median age: 40 years), 167 had history of COVID-19 (83/84, 37 years) and 143 did not (58 men/85 women, 46 years). In the COVID-19 group, 26 had long COVID (12/14, 32 years) and 141 did not (58/85, 46 years). Fewer participants in the COVID-19 group had had COVID-19 vaccinations. The long COVID group had higher number of symptoms at the time of illness and higher NEO Five Factor Inventory Neuroticism scores than the non-long COVID group. They also had poorer mental health according to HRQOL than those without.

CONCLUSION: Risk factors for long COVID may include the number of symptoms at the time of illness and neurotic tendency on NEO Five Factor Inventory. Participants with long COVID had poorer mental health according to HRQOL. People with long COVID might be especially sensitive to and pessimistic about the symptoms that interfere with their daily lives, resulting in certain cognitive and behavioral patterns. They may benefit from early psychiatric intervention.}, } @article {pmid39372136, year = {2024}, author = {He, N and Tunala, S and Wu, R and Zhao, C and Wuren, T and Hushuud, C}, title = {Knowledge, Attitudes, and Practices Among Community Populations Toward Long COVID in China.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {4455-4463}, pmid = {39372136}, issn = {1178-7074}, abstract = {PURPOSE: This study aimed to assess the knowledge, attitudes and practices (KAP) among community populations toward Long COVID.

PATIENTS AND METHODS: This cross-sectional study was conducted between March 2023 and June 2023 at the Ordos Mongolian hospital and Ordos Central Hospital in Ordos, Inner Mongolia, China, employing a self-designed questionnaire to collect demographic data from community populations and evaluate their knowledge, attitudes, and practices toward Long COVID.

RESULTS: A total of 591 participants were enrolled in this study. Among them, 343 (58.04%) were female and 317 (53.64%) aged 40 to 59 years. The mean knowledge, attitudes and practices scores were 6.02±1.19 (possible range: 0-7), 26.83±2.96 (possible range: 7-35), and 45.91±7.20 (possible range: 11-55), respectively. The Pearson's correlation analysis indicated significant positive correlations between knowledge and attitudes (r=0.210, P<0.001), and attitudes and practices (r=0.476, P<0.001). The structural equation model demonstrated that knowledge positively affect attitudes, as indicated by a path coefficient of 1.028 (P<0.001), and attitudes positively affect practices, with a path coefficient of 0.817 (P<0.001).

CONCLUSION: Although our findings indicate that community populations generally have adequate knowledge, active attitudes, and proactive practices regarding Long COVID, there is still a need for healthcare providers to further enhance Long COVID awareness in the community. This involves fostering positive attitudes through open communication, emphasizing the importance of early intervention and treatment adherence, and encouraging continued adherence to preventive measures.}, } @article {pmid39371163, year = {2024}, author = {Lorman, V and Bailey, LC and Song, X and Rao, S and Hornig, M and Utidjian, L and Razzaghi, H and Mejias, A and Leikauf, JE and Brill, SB and Allen, A and Bunnell, HT and Reedy, C and Mosa, ASM and Horne, BD and Geary, CR and Chuang, CH and Williams, DA and Christakis, DA and Chrischilles, EA and Mendonca, EA and Cowell, LG and McCorkell, L and Liu, M and Cummins, MR and Jhaveri, R and Blecker, S and Forrest, CB}, title = {Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39371163}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.}, } @article {pmid39370158, year = {2024}, author = {Thomas, J and Prgomet, M and Weeding, S and McGuire, P and Goodger, B and Joss, N and Mackintosh, CF and McLeod, A and Georgiou, A}, title = {A qualitative study of the general practice experience of diagnosing and managing long COVID: Challenges and practical recommendations.}, journal = {Australian journal of general practice}, volume = {53}, number = {10}, pages = {732-736}, doi = {10.31128/AJGP-10-23-6983}, pmid = {39370158}, issn = {2208-7958}, mesh = {Humans ; *COVID-19/diagnosis/therapy ; *Qualitative Research ; *General Practice/methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND OBJECTIVES: Patients with prolonged symptoms following COVID-19 infection(s) will increasingly present to general practice. Our research objective was to understand the general practice experience of diagnosing and managing long COVID and to explore recommendations for contributing to the safety and quality of the long COVID response.

METHOD: A two-hour qualitative session involving 11 project stakeholders was held in March 2023. The stakeholders included general practitioners as well as representatives from four Primary Health Networks, Outcome Health and the funding body. Transcripts were analysed using qualitative content analysis.

RESULTS: Key challenges and practical recommendations emerged relating to diagnosing long COVID, documentation of COVID-19 infections, ongoing management, screening tools and the need for public health messaging.

DISCUSSION: General practices need more accurate definitions and information about the diagnosis of long COVID. Supporting general practitioners with information to diagnose and manage patients with long COVID is essential. General practice voices need to be heard to enhance our understanding of long COVID and inform policy decisions.}, } @article {pmid39370044, year = {2024}, author = {Crucianelli, S and Mariano, A and Valeriani, F and Cocomello, N and Gianfranceschi, G and Baseggio Conrado, A and Moretti, F and Scotto d'Abusco, A and Mennuni, G and Fraioli, A and Del Ben, M and Romano Spica, V and Fontana, M}, title = {Effects of sulphur thermal water inhalations in long-COVID syndrome: Spa-centred, double-blinded, randomised case-control pilot study.}, journal = {Clinical medicine (London, England)}, volume = {24}, number = {6}, pages = {100251}, pmid = {39370044}, issn = {1473-4893}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Administration, Inhalation ; Case-Control Studies ; COVID-19 ; Double-Blind Method ; Pilot Projects ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; *Sulfur/administration & dosage ; Water ; }, abstract = {BACKGROUND: The long-COVID syndrome is characterised by a plethora of symptoms. Given its social and economic impact, many studies have stressed the urgency of proposing innovative strategies other than hospital settings. In this double-blinded, randomised, case-control trial, we investigate the effects of sulphur thermal water inhalations, rich in H2S, compared to distilled water inhalations on symptoms, inflammatory markers and nasal microbiome in long-COVID patients.

METHODS: About 30 outpatients aged 18-75 with positive diagnosis for long-COVID were randomised in two groups undergoing 12 consecutive days of inhalations. The active group (STW) received sulphur thermal water inhalations whereas the placebo group received inhalations of sterile distilled non-pyrogenic water (SDW). Each participant was tested prior treatment at day 1 (T0), after the inhalations at day 14 (T1) and at 3 months follow-up (T2). At each time point, blood tests, nasal swabs for microbiome sampling, pulmonary functionality tests (PFTs) and pro-inflammatory marker measure were performed.

RESULTS: The scores obtained in the administered tests (6MWT, Borg score and SGRQ) at T0 showed a significant variation in the STW group, at T1 and T2. Serum cytokine levels and other inflammatory biomarkers reported a statistically significant decrease. Some specific parameters of PFTs showed ameliorations in the STW group only. Changes in the STW nasopharyngeal microbiota composition were noticed, especially from T0 to T2.

CONCLUSIONS: Inhalations of sulphur thermal water exerted objective and subjective improvements on participants affected by long-COVID. Significant reduction of inflammatory markers, dyspnoea scores and quantitative and qualitative changes in the nasopharyngeal microbiome were also assessed.}, } @article {pmid39369845, year = {2024}, author = {Tang, CC and Chang, JC and Ho, SJ and Liu, WD and Pan, MY and Chang, SC and Wang, WS and Yeh, YC and Chen, CH and Wu, WW}, title = {Exploring the characteristics and antecedents of clinically significant long COVID: A longitudinal cohort study.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123114}, doi = {10.1016/j.lfs.2024.123114}, pmid = {39369845}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/epidemiology/psychology/complications ; Female ; Male ; Longitudinal Studies ; Middle Aged ; Adult ; *Quality of Life ; *Survivors ; SARS-CoV-2 ; Aged ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Cohort Studies ; Dyspnea/physiopathology ; }, abstract = {BACKGROUND: A significant number of coronavirus disease 2019 (COVID-19) survivors are experiencing long COVID, with symptoms lasting beyond three months. While diverse long COVID symptoms are established, there are gaps in understanding its long-term trends, intensity, and risk factors, requiring further investigation.

AIMS: This study aimed to investigate the long COVID characteristics and associated factors by following COVID-19 survivors for one year post-infection and comparing them with healthy counterparts.

MAIN METHODS: In this longitudinal, correlational study, COVID-19 survivors diagnosed between November 2021 and February 2023 were monitored every three months for a year. Participants aged ≥18 years who had reported a positive COVID-19 test were recruited via social media and healthcare provider referrals.

KEY FINDINGS: Out of 182 survivors who initially agreed to participate, 176 completed the study. The mean age was 47.56 years (SD = 16.2), and 51.1 % were female. There was a clinically significant decline in cognitive function and health-related quality of life over time, with symptoms like shortness of breath, reduced physical fitness, and increased health concerns. Those with severe acute COVID-19 symptoms experienced greater cognitive and physical declines and more shortness of breath a year later. Lower financial status was linked to poorer health-related quality of life and increased health concerns.

SIGNIFICANCE: A year post-infection, COVID-19's impact on cognitive function and health-related quality of life remains significant, affecting individuals and communities. Survivors with severe initial symptoms and economic disadvantages need more attention. Future research should identify additional predictors of severe long COVID.}, } @article {pmid39369712, year = {2024}, author = {Gallo, A and Murace, CA and Corbo, MM and Sarlo, F and De Ninno, G and Baroni, S and Fancello, G and Masucci, L and Covino, M and Tosato, M and Landi, F and Montalto, M and , }, title = {Intestinal Inflammation and Permeability in Patients Recovered from SARS-CoV-2 Infection.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-10}, doi = {10.1159/000540381}, pmid = {39369712}, issn = {1421-9875}, abstract = {INTRODUCTION: Different works suggest a close link between long COVID gastrointestinal (GI) manifestations and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae.

METHODS: Eighty-six subjects attending the post-COVID service and recovered from SARS-CoV-2 infection for 6 months were investigated for long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC) and permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and the Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants.

RESULTS: Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p = 0.03), although remaining quite close to the normal range. No significant differences were shown regarding the assessment of intestinal permeability. By GIQLI, long-term GI sequelae were inversely correlated with quality of life (p = 0.009).

CONCLUSION: Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post-COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.}, } @article {pmid39369205, year = {2024}, author = {Bhimani, P and Scheinfeld, A and Rajan, M}, title = {Emergency department utilization among children with Long COVID symptoms: a COVID-19 research consortium study.}, journal = {BMC pediatrics}, volume = {24}, number = {1}, pages = {635}, pmid = {39369205}, issn = {1471-2431}, mesh = {Humans ; *COVID-19/epidemiology ; *Emergency Service, Hospital/statistics & numerical data ; Female ; Child ; Male ; Child, Preschool ; Adolescent ; Infant ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; United States/epidemiology ; Databases, Factual ; }, abstract = {BACKGROUND AND OBJECTIVES: Long COVID, characterized by persistent symptoms beyond the acute infection phase, remains poorly characterized in children. Our study aim is to determine if children who exhibit any symptoms/conditions associated with Long COVID after acute COVID-19 infection have higher Emergency Department (ED) utilization compared to those who do not exhibit these symptoms.

METHODS: Data from the HealthJump ambulatory database from the COVID-19 Research Database Consortium was utilized to identify pediatric COVID-19 cases from March 2020 to May 2023. Long COVID cases were defined based on symptoms/conditions occurring 30-180 days after initial COVID diagnosis. Descriptive statistics and multivariable logistic regression models were used to model the relationship between Long COVID and child ED utilization.

RESULTS: Out of 130,010 children diagnosed with COVID-19, 43,645 (33.6%) exhibited at least one Long COVID symptom/condition. Children with Long COVID symptoms/conditions had 152% higher odds (OR: 2.52, CI: 2.32-2.73) of ED visits, while those with specific symptoms including "chest pain" had 255% higher odds (AOR: 3.55, CI: 2.73-4.54) and "fluid and electrolyte disturbances" had 229% higher odds (AOR: 3.29, CI: 2.23-4.73) compared to those without those symptoms/conditions.

CONCLUSION: This study reveals that children with Long COVID symptoms had notably higher odds of ED visits, with chest pain, fluid imbalances, and generalized pain being most closely linked to such visits. This study highlights the burden of Long COVID on ED providers and underscores the importance of improved guidance for managing Long COVID symptoms in children.}, } @article {pmid39369190, year = {2024}, author = {Hermann, A and Benke, C and Blecker, CR and de Haas, B and He, Y and Hofmann, SG and Iffland, JR and Jengert-Stahl, J and Kircher, T and Leinweber, K and Linka, M and Mulert, C and Neudert, MK and Noll, AK and Melzig, CA and Rief, W and Rothkopf, C and Schäfer, A and Schmitter, CV and Schuster, V and Stark, R and Straube, B and Zimmer, RI and Kirchner, L}, title = {Study protocol TransTAM: Transdiagnostic research into emotional disorders and cognitive-behavioral therapy of the adaptive mind.}, journal = {BMC psychiatry}, volume = {24}, number = {1}, pages = {657}, pmid = {39369190}, issn = {1471-244X}, support = {LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; LOEWE1/16/519/03/09.001(0009)/98//LOEWE Center DYNAMIC/ ; SFB/TRR393//German Research Foundation/ ; SFB/TRR393//German Research Foundation/ ; SFB/TRR393//German Research Foundation/ ; }, mesh = {Humans ; *Cognitive Behavioral Therapy/methods ; Adult ; Anxiety Disorders/therapy/diagnosis ; Germany ; Female ; Male ; Prospective Studies ; Depressive Disorder/therapy/diagnosis ; }, abstract = {BACKGROUND: Emotional disorders such as depression and anxiety disorders share substantial similarities in their etiology and treatment. In recent decades, these commonalities have been increasingly recognized in classification systems and treatment programs crossing diagnostic boundaries.

METHODS: To examine the prospective effects of different transdiagnostic markers on relevant treatment outcomes, we plan to track a minimum of N = 200 patients with emotional disorders during their routine course of cognitive behavioral therapy at two German outpatient clinics. We will collect a wide range of transdiagnostic markers, ranging from basic perceptual processes and self-report measures to complex behavioral and neurobiological indicators, before entering therapy. Symptoms and psychopathological processes will be recorded before entering therapy, between the 20th and 24th therapy session, and at the end of therapy.

DISCUSSION: Our results could help to identify transdiagnostic markers with high predictive power, but also provide deeper insights into which patient groups with which symptom clusters are less likely to benefit from therapy, and for what reasons.

TRIAL REGISTRATION: The trial was preregistered at the German Clinical Trial Register (DRKS-ID: DRKS00031206; 2023-05-09).}, } @article {pmid39368535, year = {2024}, author = {Raza, ML and Imam, MH and Zehra, W and Jamil, S}, title = {Neuro-inflammatory pathways in COVID-19-induced central nervous system injury: Implications for prevention and treatment strategies.}, journal = {Experimental neurology}, volume = {382}, number = {}, pages = {114984}, doi = {10.1016/j.expneurol.2024.114984}, pmid = {39368535}, issn = {1090-2430}, mesh = {Humans ; *COVID-19/complications/immunology ; *Neuroinflammatory Diseases/etiology/immunology ; *SARS-CoV-2 ; Cytokine Release Syndrome/etiology/prevention & control ; Blood-Brain Barrier ; Animals ; Microglia ; }, abstract = {This review explores the neuroinflammatory pathways underlying COVID-19-induced central nervous system (CNS) injury, with a focus on mechanisms of brain damage and strategies for prevention. A comprehensive literature review was conducted to summarize current knowledge on the pathways by which SARS-CoV-2 reaches the brain, the neuroinflammatory responses triggered by viral infection, neurological symptoms and long COVID. Results: We discuss the mechanisms of neuroinflammation in COVID-19, including blood-brain barrier disruption, cytokine storm, microglial activation, and peripheral immune cell infiltration. Additionally, we highlight potential strategies for preventing CNS injury, including pharmacological interventions, immunomodulatory therapies, and lifestyle modifications. Conclusively, Understanding the neuroinflammatory pathways in COVID-19-induced CNS injury is crucial for developing effective prevention and treatment strategies to protect brain health during and after viral infection.}, } @article {pmid39367848, year = {2024}, author = {Edwards, DL and Shah, MM and Shi, DS and Ford, ND and Rinsky, JL and Jones, JM and Spencer, B and Haynes, J and Saydah, SH}, title = {Occupational and industry prevalence of new long-term symptoms within American Red Cross blood donors with and without history of SARS-CoV-2 infection.}, journal = {American journal of industrial medicine}, volume = {67}, number = {12}, pages = {1108-1120}, doi = {10.1002/ajim.23670}, pmid = {39367848}, issn = {1097-0274}, support = {/CC/CDC HHS/United States ; 75D30121P11093//American Red Cross/ ; /CC/CDC HHS/United States ; }, mesh = {Humans ; *Blood Donors/statistics & numerical data ; *COVID-19/epidemiology ; Male ; Female ; Adult ; *Red Cross ; Middle Aged ; Prevalence ; United States/epidemiology ; *SARS-CoV-2 ; Occupations/statistics & numerical data ; Adolescent ; Young Adult ; Self Report ; Industry/statistics & numerical data ; Aged ; Surveys and Questionnaires ; }, abstract = {PURPOSE: Limited information is known about the burden of Long COVID by occupation and industry. This study compares the occurrence of self-reported new long-term symptoms lasting 4 weeks or longer among blood donors with and without prior SARS-CoV-2 infection by occupation and industry.

METHODS: The American Red Cross invited blood donors 18 years and older who donated during May 4-December 31, 2021 to participate in online surveys. New long-term symptoms lasting 4 weeks or longer were assessed by self-reported occurrence of any of 35 symptoms since March 2020. SARS-CoV-2 infection status was determined by serological testing and self-report. We describe the prevalence of new long-term symptoms by SARS-CoV-2 infection status. We calculate the difference in reported new long-term symptoms by SARS-CoV-2 infection status within occupation and industry categories.

RESULTS: Data were collected from 27,907 employed adults - 9763 were previously infected and 18,234 were never infected with SARS-CoV-2. New long-term symptoms were more prevalent among those previously infected compared to the never-infected respondents (45% vs 24%, p < 0.05). Among all respondents, new long-term symptoms by occupation ranged from 26% (installation, maintenance, and repair) to 41% (healthcare support) and by industry ranged from 26% (mining) to 55% (accommodation and food services). New long-term neurological and other symptoms were commonly reported by those previously infected with SARS-CoV-2.

DISCUSSION: New long-term symptoms are more prevalent among certain occupation and industry groups, which likely reflects differential exposure to SARS-CoV-2. These findings highlight potential need for workplace accommodations in a variety of occupational settings to address new long-term symptoms.}, } @article {pmid39367278, year = {2024}, author = {Hasenöhrl, T and Scharer, B and Steiner, M and Schmeckenbecher, J and Jordakieva, G and Crevenna, R}, title = {Facilitators and barriers of long-term exercise adherence in healthcare workers formerly suffering from post-COVID-19 syndrome : A qualitative 1-year follow-up and quantitative pilot study of the COFIT trial.}, journal = {Wiener klinische Wochenschrift}, volume = {136}, number = {21-22}, pages = {608-618}, pmid = {39367278}, issn = {1613-7671}, mesh = {Humans ; *COVID-19/psychology/prevention & control ; Pilot Projects ; Male ; Female ; Adult ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Exercise Therapy/methods ; Follow-Up Studies ; Health Personnel/psychology ; SARS-CoV-2 ; Exercise/psychology ; Qualitative Research ; Patient Compliance/statistics & numerical data/psychology ; }, abstract = {BACKGROUND: Early exercise intervention studies showed promising positive effects of physical exercising on post-COVID-19 symptoms; however, little is known about long-term training adherence and what influences it.

MATERIAL AND METHODS: Semi-structured interviews were conducted with 17 participants of the 8‑week original exercise intervention study. Facilitators and barriers were identified via thematic analysis and compared between those participants who continued their regular exercise behavior (continuous exercise group, CEG, n = 7) and those who stopped exercising (discontinuous exercise group, DEG, n = 10). Physical performance parameters and questionnaires regarding psychological health dimensions and work ability were assessed analogously to the original study.

RESULTS: Qualitative analysis showed that two of the top three facilitators, (improving physical and mental health, sport has high priority) were the same in both groups. The respective third of the top three facilitators was (re)build physical and cognitive performance in the CEG and training in the group in the DEG. The top three barriers (exhaustion, sport has little priority, procrastination) were not only the same in both groups but also in the same order.

CONCLUSION: The strongest post-COVID-19 associated facilitator for long-term exercise adherence is when the need for further reconditioning is felt. The strongest post-COVID-19 associated barrier is exhaustion. Availability of exercising in a group is a key factor in increasing long-term exercise adherence.}, } @article {pmid39366339, year = {2024}, author = {Fitzgerald, ML and Cohen, AK and Jaudon, TW and Vogel, JM and Koppes, AN and Santos, L and Robles, R and Lin, J and Davids, JD and McWilliams, C and Redfield, S and Banks, KP and Richardson, M and Tindle Akintonwa, TT and Pollack, B and Spier, E and Weiss, A and Assaf, G and Davis, H and McCorkell, L}, title = {A call from patient-researchers to advance research on long COVID.}, journal = {Cell}, volume = {187}, number = {20}, pages = {5490-5496}, doi = {10.1016/j.cell.2024.09.011}, pmid = {39366339}, issn = {1097-4172}, mesh = {Humans ; *COVID-19/virology/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Biomedical Research ; Research Personnel ; }, abstract = {Long COVID is a chronic and often disabling illness with long-term consequences. Although progress has been made in the clinical characterization of long COVID, no approved treatments exist and disconnects between patients and researchers threaten to hinder future progress. Incorporating patients as active collaborators in long COVID research can bridge the gap and accelerate progress toward treatments and cures.}, } @article {pmid39365220, year = {2024}, author = {Gross, M and Lansang, N and Gopaul, U and Yoney, K and Ogawa, EF and Heyn, PC and Sood, P and Omar, Z and Zanwar, PP and Schwertfeger, J and Faieta, J}, title = {What Do I Need to Know About Long COVID-related Breathing Problems?.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {12}, pages = {2401-2405}, doi = {10.1016/j.apmr.2024.06.024}, pmid = {39365220}, issn = {1532-821X}, } @article {pmid39364804, year = {2024}, author = {Laguarta-Val, S and Carratalá-Tejada, M and Molina-Rueda, F and Moreta-Fuentes, R and Fernández-Vázquez, D and López-González, R and Jiménez-Antona, C and Moreta-Fuentes, C and Fidalgo-Herrera, AJ and Miangolarra-Page, JC and Navarro-López, V}, title = {Effects of a plank-based strength training programme on muscle activation in patients with long COVID: a case series.}, journal = {Anales del sistema sanitario de Navarra}, volume = {47}, number = {3}, pages = {}, pmid = {39364804}, issn = {2340-3527}, mesh = {Humans ; Female ; Middle Aged ; *COVID-19 ; Male ; Adult ; *Resistance Training/methods ; *Electromyography ; Muscle Strength/physiology ; Muscle, Skeletal/physiology ; Muscle Fatigue/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: This study aimed to analyse the effects of a plank-based strength training programme on muscle activation in patients with long COVID.

SUBJECTS AND METHODS: Case series study that included patients with long COVID who participated in a 12-week trunk and pelvic muscle strength training programme. Clinical variables and the modified fatigue impact scale (MFIS) were used to assess fatigue levels. Percentage of muscle activation during a core muscle plank was measured via surface electromyography. Pre- and post-intervention results were compared using the Wilcoxon signed-rank test and evaluated with Cohen's D effect size (ES).

RESULTS: Twenty-one subjects participated in the study; 81% female, mean age 47.5 years (range: 28-55 years), and median duration of symptoms 21 months (range: 5-24 months); 90.5% of the participants experienced fatigue (MFIS score = 38). Muscle activation during plank exercises improved across all muscles after the intervention, with significant increases in the left (p = 0.011, medium ES) and right external oblique (p =0.039, small ES) muscles and the right latissimus dorsi muscle (p = 0.039, small ES). Additionally, significant reductions in fatigue were observed in the total MFIS score (p = 0.004, medium ES) and in the physical (p < 0.001, large ES) and psychosocial subscales (p = 0.033, small ES).

CONCLUSIONS: Results suggest that a plank-based strength training programme may be effective in enhancing trunk and pelvic muscle activation in individuals with long COVID.}, } @article {pmid39363376, year = {2024}, author = {Bai, B and Xu, M and Zhou, H and Liao, Y and Liu, F and Liu, Y and Yuan, Y and Geng, Q and Ma, H}, title = {Effects of aerobic training on cardiopulmonary fitness in patients with long COVID-19: a randomized controlled trial.}, journal = {Trials}, volume = {25}, number = {1}, pages = {649}, pmid = {39363376}, issn = {1745-6215}, mesh = {Humans ; *COVID-19 ; Male ; Female ; Middle Aged ; *Cardiorespiratory Fitness ; Adult ; Aged ; *Exercise Therapy/methods ; SARS-CoV-2 ; Treatment Outcome ; Young Adult ; Adolescent ; Exercise ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID-19 is characterized by systemic deterioration of the entire body, leading to significant physical and mental disorders. Exercise training has the potential to improve persistent symptoms and cardiopulmonary functions.

METHOD: This was a single-center, randomized, controlled trial. Twenty-four patients aged 18 to 75 years who had a history of SARS-CoV-2 infection and long COVID symptoms. Patients were randomly allocated in a 1:1 ratio to receive either a 4-week exercise training program or an attention control group. The training group participated in 12 supervised aerobic sessions on a cycling ergometer over 4 weeks. The outcomes were to assess the impact of a 4-week aerobic exercise on the persistent symptoms and cardiopulmonary fitness, the surrogate endpoints of COVID-19 recovery and cardiopulmonary health.

RESULTS: After the 4-week intervention, significant reductions were observed in the total number of symptoms in the training group. Specifically, 67.8% of patients in the training group exhibited reduced or completely resolved symptoms, in comparison to 16.7% in the control group (P = 0.013). After adjusting for gender, significant improvements in the training group were observed for exercise time (Pgroup*time = 0.028), maximum load (Pgroup*time = 0.01), and peak VO2 (Pgroup*time = 0.001), as well as O2 pulse (Pgroup*time = 0.042) and maximum heart rate (Pgroup*time = 0.007). The score of Short Form-12, depression, anxiety, perceived stress, and insomnia did not show significant changes between groups (Pgroup*time > 0.05).

CONCLUSION: A supervised aerobic training program has the potential to alleviate persistent symptoms and improve exercise tolerance in patients with long COVID-19. Further research is necessary to confirm these effects in a large population. This intervention could be easily implemented in non-hospital settings, potentially benefiting a broader range of individuals.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05961462. Registered on July 25, 2023.}, } @article {pmid39361178, year = {2024}, author = {Specktor, P and Hadar, D and Cohen, H}, title = {Glucocorticoid treatment during COVID-19 infection: does it affect the incidence of long COVID?.}, journal = {Inflammopharmacology}, volume = {32}, number = {6}, pages = {3707-3715}, pmid = {39361178}, issn = {1568-5608}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; *Glucocorticoids/therapeutic use/adverse effects ; Middle Aged ; Aged ; Incidence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Adult ; Retrospective Studies ; Sex Factors ; SARS-CoV-2 ; Aged, 80 and over ; }, abstract = {BACKGROUND: Long COVID (LC) is a frequent complication of COVID infection. It usually results in cognitive impairment, myalgia, headache and fatigue. No effective treatment has been found yet. We aimed to explore the effect of glucocorticoid (GC) treatment during COVID-19 infection on the later development of LC.

METHODS: We examined electronic health records from Clalit Health Services for documentation of COVID-19, GC treatment, and LC frequency. Background diagnoses, demographic data, hospitalization rates, and the use of anti-COVID drugs were recorded.

RESULTS: 1,322,599 cases of COVID-19 infection met the inclusion criteria; 13,530 patients (1.02%) received GC treatment. 149,272 patients, 11.29% of COVID-19 patients were diagnosed with LC. Age and female gender were prognostic risk factors for LC (OR 1.06 for age, OR 1.4 for female gender; p value < 0.0001). Background psychiatric diagnoses, migraine, backache and irritable bowel syndrome were predisposing conditions for LC (OR 2.7, p value < .0001). Higher BMI was associated with a greater probability of LC (OR of 1.25 for obese population). COVID patients who received GC were diagnosed with LC more frequently: 2294 cases (16.95%) compared to 146,978 cases (11.23%) in the non-GC group; (adjusted OR of 1.28 ± 0.07, 95% CI, p < 0.0001).

CONCLUSIONS: GC treatment during COVID-19 is correlated with the development of LC. In vivo and animal models may be used to explore the mechanism of this correlation. Future directions include prospective studies as well.}, } @article {pmid39361124, year = {2024}, author = {Weigel, B and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S}, title = {A pilot cross-sectional investigation of symptom clusters and associations with patient-reported outcomes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {12}, pages = {3229-3243}, pmid = {39361124}, issn = {1573-2649}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology/physiopathology ; Female ; Male ; *Patient Reported Outcome Measures ; Adult ; Middle Aged ; *COVID-19/complications/psychology ; Cross-Sectional Studies ; Pilot Projects ; *Quality of Life ; SARS-CoV-2 ; Australia ; Aged ; Young Adult ; Adolescent ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Cluster Analysis ; }, abstract = {BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with long-term disability and poor quality of life (QoL). Cardinal ME/CFS symptoms (including post-exertional malaise, cognitive dysfunction and sleep disturbances) have been observed in Post COVID-19 Condition (PCC). To gain further insight into the potential role of ME/CFS as a post-COVID-19 sequela, this study investigates associations between symptoms and patient-reported outcomes, as well as symptom clusters.

METHODS: Participants included Australian residents aged between 18 and 65 years formally diagnosed with ME/CFS fulfilling the Canadian or International Consensus Criteria or PCC meeting the World Health Organization case definition. Validated, self-administered questionnaires collected participants' sociodemographic and illness characteristics, symptoms, QoL and functional capacity. Associations between symptoms and patient-reported outcomes were investigated with multivariate linear regression models. Hierarchical cluster analysis was performed to identify symptom clusters.

RESULTS: Most people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) were female (n = 48/60, 80.0% and n = 19/30, 63.3%, respectively; p = 0.12). PwME/CFS were significantly younger (x̄=41.75, s = 12.91 years) than pwPCC (x̄=48.13, s =10.05 years; p =0.017). Autonomic symptoms (notably dyspnoea) were associated with poorer scores in most patient-reported outcome domains for both cohorts. None of the four symptom clusters identified were unique to ME/CFS or PCC. Clusters were largely delineated by the presence of gastrointestinal and neurosensory symptoms, illness duration, ME/CFS criteria met and total symptoms.

CONCLUSIONS: Illness duration may explain differences in symptom burden between pwME/CFS and pwPCC. PCC diagnostic criteria must be refined to distinguish pwPCC at risk of long-term ME/CFS-like illness and subsequently deliver necessary care and support.}, } @article {pmid39360869, year = {2024}, author = {Kleebayoon, A and Wiwanitkit, V}, title = {Sleep and long COVID.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {}, number = {}, pages = {}, doi = {10.5664/jcsm.11410}, pmid = {39360869}, issn = {1550-9397}, } @article {pmid39360535, year = {2024}, author = {Amdani, S and Altman, CA and Chowdhury, D and Ronai, C and Soma, D and Archer, JM and Tierney, S and Renno, MS and Miller, J and Nguyen, QT and Glickstein, JS and Orr, WB}, title = {Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection.}, journal = {Current pediatric reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115733963314978240923110844}, pmid = {39360535}, issn = {1875-6336}, abstract = {The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-- CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.}, } @article {pmid39358980, year = {2024}, author = {Baz, SA and Woodrow, M and Clutterbuck, D and Fang, C and Mullard, J and Banerjee, A and Barley-McMullen, S and Carpentieri, J and Donskoy, AL and Faux-Nightingale, A and Lewis-Jackson, S and O'Hara, ME and Rai, T and Sherwood, O and Smyth, N and Stanley, K and Welsh, V and Mir, G and Alwan, NA}, title = {Long COVID and Health Inequalities: What's Next for Research and Policy Advocacy?.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {5}, pages = {e70047}, pmid = {39358980}, issn = {1369-7625}, support = {//The CONVALESCENCE project funding (funders UKRI MC_PC_20051 and National Institute for Health and Care Research [NIHR] COV-LT-0009) funded the QLC network special theme workshop on 'Long Covid and Health Inequalities'./ ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Health Policy ; Post-Acute COVID-19 Syndrome ; Health Services Accessibility/organization & administration ; Social Stigma ; Healthcare Disparities ; Health Status Disparities ; Health Inequities ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Organised by the 'Qualitative Long Covid Network', a workshop for qualitative Long COVID (LC) researchers, LC charity representatives and people with LC took place in June 2023, where research on the intersectional inequalities affecting LC prevalence, recognition and care was shared and discussed.

METHODS: Five key themes were drawn up from presentations, discussions and reflections during the workshop, which are presented in this study.

RESULTS: The following five themes are discussed: the unfairness of LC, difficulties in accessing care, mistrust of the healthcare system, a lack of understanding of LC and experiences of stigma and discrimination. Factors that widen or narrow inequalities related to LC were identified.

CONCLUSION: A call to action is proposed to investigate and address inequalities through a robust LC research agenda that speaks with conviction to policy and decision-makers. We argue that there needs to be a strong investment in research and evidence-based policy and practice to mitigate the worst effects of the condition and address the inequalities in experience, treatment and support, which are experienced more often and more acutely by some of society's most vulnerable and disadvantaged individuals.

Projects included in this article had PPI ongoing activity to inform their research. A member of the CONVALESCENCE PPI group presented at the QLC Network 'Long Covid and Health Inequalities' workshop, as did members of Long COVID Kids, Long COVID Support and Long COVID SOS charities. They were all invited to be co-authors of this article.}, } @article {pmid39358973, year = {2024}, author = {Adams, NN and MacIver, E and Douglas, F and Kennedy, C and Skåtun, D and Hernandez Santiago, V and Torrance, N and Grant, A}, title = {Disrupted Candidacy: A Longitudinal Examination of the Constrained Healthcare-Access Journeys of National Health Service Workers in Scotland Seeking Supports for Long COVID Illness.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {5}, pages = {e70050}, pmid = {39358973}, issn = {1369-7625}, support = {//This study was supported by the Chief Scientist Office (Grant Reference: COV/LTE/20/32)./ ; }, mesh = {Humans ; Scotland ; *State Medicine ; *COVID-19/psychology ; Longitudinal Studies ; Male ; Female ; *Qualitative Research ; *Health Personnel/psychology ; *Health Services Accessibility ; Adult ; Middle Aged ; Interviews as Topic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Evidence examines how persons experiencing Long COVID (LC) struggle to secure healthcare for symptoms. However, few studies examine healthcare workers experiencing LC, nor the complex and multiple difficulties faced when seeking and receiving healthcare.

METHODS: This study is based on two phases of longitudinally conducted qualitative interviews, 6 months apart, with National Health Service (NHS) workers experiencing LC, from different occupational roles at NHS locales in Scotland (first interviews, n = 50; second interviews, n = 44).

RESULTS: Multiple factors restricted healthcare access, including worries about pressuring the NHS and concerns over LC being legitimised. When healthcare was sought, workers struggled to secure support, referrals and treatment. The following reasons were included: (1) context: the restrictive pandemic healthcare context; (2) illness climate: low GP knowledge surrounding LC and how this could be treated, trends for ascribing symptoms to other causes and reluctance to diagnose LC; (3) sense-making of LC: healthcare availability linked to occupational role identity. To visualise and examine healthcare barriers, candidacy theory is applied, drawing inferences between healthcare context, illness climate, sense-making and identities.

CONCLUSION: NHS workers' complex journeys represent Disrupted Candidacy, intersecting challenges across candidacy domains, restricting the seeking and receiving of LC healthcare. Findings provide insights into why NHS workers resisted and withdrew from healthcare-seeking, and the barriers they faced when attempting to secure LC support. This study presents a pathway for future LC illness research to use a modified candidacy theory framework.

This research focuses on amplifying and learning from lived experiences, and the voices of NHS workers in Scotland experiencing LC. Interviews represent primary data for this study; thus, participants and their healthcare journeys are centred in this research and all aspects of production, reporting and output. Explicit discussions of stakeholder group involvement are highlighted in the methods section.}, } @article {pmid39358543, year = {2024}, author = {Victoria, LW and Oberlin, LE and Ilieva, IP and Jaywant, A and Kanellopoulos, D and Mercaldi, C and Stamatis, CA and Farlow, DN and Kollins, SH and Tisor, O and Joshi, S and Doreste-Mendez, R and Perlis, RH and Gunning, FM}, title = {A digital intervention for cognitive deficits following COVID-19: a randomized clinical trial.}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {50}, number = {2}, pages = {472-479}, pmid = {39358543}, issn = {1740-634X}, mesh = {Humans ; Female ; Male ; *COVID-19/complications/psychology ; Middle Aged ; *Cognitive Dysfunction/etiology/therapy/psychology ; Adult ; Executive Function/physiology ; Telemedicine ; Treatment Outcome ; Attention ; }, abstract = {Post-COVID-19 cognitive deficits are common, persistent, and disabling. Evidence on effective treatments is limited. The goal of this study was to investigate the efficacy of a digital intervention to reduce cognitive and functional deficits in adults with persistent post-COVID-19 cognitive dysfunction. We used the remotely-delivered intervention in a randomized clinical trial conducted from July 13, 2021 to April 26, 2023. We hypothesized that participants in the intervention group would improve in measures of cognition and daily functioning. Participants were adults with cognitive deficits persisting >4 weeks following acute COVID-19 illness. Of 183 participants screened, 110 were enrolled; 98 participants (78.6% female; mean age = 48.1) completed at least one study visit. Participants were randomized 1:1 to the intervention (AKL-T01) or waitlist control. AKL-T01 is a digital therapeutic using a videogame interface to target attention and executive control. The intervention was delivered remotely for 6 weeks. The primary outcome was change in performance on a sustained attention measure (Digit Symbol Matching Task). The difference in the primary outcome between the intervention (n = 49) and controls (n = 49) was not statistically significant (F [3,261] = 0.12, p = 0.95). Secondary cognitive outcomes of task-switching (F[3,262] = 2.78, p = 0.04) and processing speed (F[3,267] = 4.57, p = 0.004) improved in the intervention relative to control. Secondary measures of functioning also improved in the intervention relative to control, including disability (F[1,82] = 4.02, p = 0.05) and quality of life (F[3,271] = 2.66, p = 0.05). Exploratory analyses showed a greater reduction in total fatigue (F[1,85] = 4.51, p = 0.04), cognitive fatigue (F[1,85] = 7.20, p = 0.009), and anxiety (F[1,87] = 7.42, p = 0.008) in the intervention relative to control. Despite the lack of improvement in sustained attention, select post-COVID-19 cognitive deficits may be ameliorated by targeted cognitive training with AKL-T01, with associated improvements in quality of life and fatigue. If replicated, the scalable nature of this digital intervention may help address substantial need for accessible, effective treatments among individuals with long COVID.}, } @article {pmid39358535, year = {2024}, author = {Peluso, MJ and Ely, EW}, title = {How long COVID could lift the fog on neurocognitive disorders.}, journal = {Nature}, volume = {634}, number = {8032}, pages = {S11}, doi = {10.1038/d41586-024-03047-4}, pmid = {39358535}, issn = {1476-4687}, mesh = {Humans ; *Neurocognitive Disorders/virology/etiology ; *Post-Acute COVID-19 Syndrome/complications/virology ; Mental Fatigue/etiology/virology ; *Biomedical Research/trends ; }, } @article {pmid39357795, year = {2024}, author = {King, LR}, title = {Gastrointestinal manifestations of long COVID.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123100}, doi = {10.1016/j.lfs.2024.123100}, pmid = {39357795}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications ; *Gastrointestinal Diseases/etiology/virology/physiopathology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; Dysbiosis/complications ; Gastrointestinal Tract/virology/physiopathology ; Irritable Bowel Syndrome/etiology/physiopathology/virology ; }, abstract = {Long COVID is estimated to have affected 6.9 % of US adults, 17.8 million people in the US alone, as of early 2023. While SARS-CoV-2 is primarily considered a respiratory virus, gastrointestinal (GI) symptoms are also frequent in patients with coronavirus disease 2019 (COVID-19) and in patients with Long COVID. The risk of developing GI symptoms is increased with increasing severity of COVID-19, the presence of GI symptoms in the acute infection, and psychological distress both before and after COVID-19. Persistence of the virus in the GI tract, ensuing inflammation, and alteration of the microbiome are all likely mediators of the effects of SARS Co-V-2 virus on the gut. These factors may all increase intestinal permeability and systemic inflammation. GI inflammation and dysbiosis can change the absorption and metabolism of tryptophan, an important neurotransmitter. Long COVID GI symptoms resemble a Disorder of Gut Brain Interaction (DGBI) such as post infection Irritable Bowel Syndrome (IBS). Current standards of treatment for IBS can guide our treatment of Long COVID patients. Dysautonomia, a frequent Long COVID condition affecting the autonomic nervous system, can also affect the GI tract, and must be considered in Long COVID patients with GI symptoms. Long COVID symptoms fall within the broader category of Infection Associated Chronic Conditions (IACCs). Research into the GI symptoms of Long COVID may further our understanding of other post infection chronic GI conditions, and elucidate the roles of therapeutic options including antivirals, probiotics, neuromodulators, and treatments of dysautonomia.}, } @article {pmid39353473, year = {2024}, author = {Dehlia, A and Guthridge, MA}, title = {The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis.}, journal = {The Journal of infection}, volume = {89}, number = {6}, pages = {106297}, doi = {10.1016/j.jinf.2024.106297}, pmid = {39353473}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/complications/physiopathology/virology ; *Fatigue Syndrome, Chronic/diagnosis/physiopathology/virology ; *Post-Acute COVID-19 Syndrome/diagnosis/physiopathology/virology ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.

METHODS: Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.

RESULTS: We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.

CONCLUSIONS: Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.}, } @article {pmid39356507, year = {2024}, author = {Guttuso, T and Zhu, J and Wilding, GE}, title = {Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {7}, number = {10}, pages = {e2436874}, pmid = {39356507}, issn = {2574-3805}, mesh = {Humans ; Female ; Male ; Middle Aged ; Double-Blind Method ; *Fatigue/drug therapy/etiology ; *Cognitive Dysfunction/drug therapy/etiology ; *COVID-19/complications ; *Aspartic Acid ; Aged ; Adult ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; }, abstract = {IMPORTANCE: Neurologic post-COVID-19 condition (PCC), or long COVID, symptoms of fatigue and cognitive dysfunction continue to affect millions of people who have been infected with SARS-CoV-2. There currently are no effective evidence-based therapies available for treating neurologic PCC.

OBJECTIVE: To assess the effects of lithium aspartate therapy on PCC fatigue and cognitive dysfunction.

A randomized, double-blind, placebo-controlled trial (RCT) enrolling participants in a neurology clinic from November 28, 2022, to June 29, 2023, with 3 weeks of follow-up, was conducted. Subsequently, an open-label lithium dose-finding study with 6 weeks of follow-up was performed among the same participants enrolled in the RCT. Eligible individuals needed to report new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19, Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or greater, Beck Depression Inventory-II score less than 24, and no history of a condition known to cause fatigue or cognitive dysfunction. All participants in the RCT were eligible for the dose-finding study, except for those who responded to the placebo. Intention-to-treat analysis was used.

INTERVENTION: Lithium aspartate, 10 to 15 mg/d, or identically appearing placebo for 3 weeks followed by open-label lithium aspartate, 10 to 15 mg/d, for 2 weeks. In the subsequent dose-finding study, open-label lithium aspartate dosages up to 45 mg/d for 6 weeks were given.

MAIN OUTCOMES AND MEASURES: Change in sum of FSS-7 and BFSS scores. The scores for each measure range from 7 to 49, with higher scores indicating more severe symptoms. Secondary outcomes included changes from baseline in the scores of additional questionnaires.

RESULTS: Fifty-two participants were enrolled (30 [58%] males; mean [SD] age, 58.54 [14.34] years) and 26 were randomized to treatment with lithium aspartate (10 females) and 26 to placebo (12 female). Two participants assigned to lithium aspartate were lost to follow-up and none withdrew. No adverse events were attributable to lithium therapy. There were no significant intergroup differences for the primary outcome (-3.6; 95% CI, -16.6 to 9.5; P = .59) or any secondary outcomes. Among 3 patients completing a subsequent dose-finding study, open-label lithium aspartate, 40 to 45 mg/d, was associated with numerically greater reductions in fatigue and cognitive dysfunction scores than 15 mg/d, particularly in 2 patients with serum lithium levels of 0.18 and 0.49 mEq/L compared with 1 patient with a level of 0.10 mEq/L.

CONCLUSIONS AND RELEVANCE: In this RCT, therapy with lithium aspartate, 10 to 15 mg/d, was ineffective for neurologic PCC fatigue and cognitive dysfunction. Another RCT is required to assess the potential benefits of higher lithium dosages for treating neurologic PCC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05618587 and NCT06108297.}, } @article {pmid39355045, year = {2023}, author = {Kimura, RH and Iagaru, A and Guo, HH}, title = {Mini review of first-in-human integrin αvβ6 PET tracers.}, journal = {Frontiers in nuclear medicine}, volume = {3}, number = {}, pages = {1271208}, pmid = {39355045}, issn = {2673-8880}, abstract = {This mini review of clinically-evaluated integrin αvβ6 PET-tracers reveals distinct differences in human-biodistribution patterns between linear peptides, including disulfide-stabilized formats, compared to head-to-tail cyclized peptides. All PET tracers mentioned in this mini review were able to delineate disease from normal tissues, but some αvβ6 PET tracers are better than others for particular clinical applications. Each αvβ6 PET tracer was validated for its ability to bind integrin αvβ6 with high affinity. However, all the head-to-tail cyclized peptide PET-tracers reviewed here did not accumulate in the GI-tract, in striking contrast to the linear and disulfide-bonded counterparts currently undergoing clinical evaluation in cancer, IPF and long COVID. Multiple independent investigators have reported the presence of β6 mRNA as well as αvβ6 protein in the GI-tract. Currently, there remains further need for biochemical, clinical, and structural data to satisfactorily explain the state-of-the-art in human αvβ6-imaging.}, } @article {pmid39354691, year = {2024}, author = {Matsubayashi, T and Yokoyama, K and Tateishi, U and Yokota, T and Sanjo, N}, title = {Specifically Decreased Thalamic Blood Flow Following COVID-19 Infection.}, journal = {Clinical nuclear medicine}, volume = {49}, number = {11}, pages = {1041-1043}, doi = {10.1097/RLU.0000000000005478}, pmid = {39354691}, issn = {1536-0229}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; Female ; Adult ; *Thalamus/diagnostic imaging/blood supply/physiopathology ; *Cerebrovascular Circulation ; *Tomography, Emission-Computed, Single-Photon ; }, abstract = {Although long COVID refers to numerous COVID-19-related symptoms after infection, including depression, fatigue, anosmia, sleep disturbances, and brain fog, the etiology of long COVID remains largely unknown. A 41-year-old woman presented with a 3-week history of complete insomnia without drowsiness throughout the day after contracting COVID-19. SPECT using N -isopropyl-p-[ 123 I] iodoamphetamine showed a significant regional cerebral blood flow reduction in the bilateral thalamus. We diagnosed her as having insomnia accompanied by thalamic hypoperfusion related to COVID-19 infection. To our knowledge, this is the first case of reduced regional cerebral blood flow specifically confined to the thalamus.}, } @article {pmid39354396, year = {2024}, author = {Abbas, U and Ahmed, I and Afshan, S and Jogezai, ZH and Kumar, P and Ahsan, A and Rehan, F and Hussain, N and Faheem, S and Baloch, IA and Yameen, M}, title = {Impact of SARS-CoV-2 viral load on restrictive spirometry patterns in mild COVID-19 recovered middle-aged individuals: a six-month prospective study.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1089}, pmid = {39354396}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/physiopathology/virology/diagnosis ; Male ; Female ; Middle Aged ; *Spirometry ; *Viral Load ; Prospective Studies ; Adult ; *SARS-CoV-2 ; Lung/physiopathology/virology ; }, abstract = {BACKGROUND: Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6-8 months of acute infection.

METHODS: This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30-60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6-8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection.

RESULTS: We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23).

CONCLUSION: In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6-8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid39354320, year = {2025}, author = {Mamani-Huanca, M and Martínez, S and López-López, Á and López-Gonzálvez, Á and Albóniga, OE and Gradillas, A and Barbas, C and González-Ruiz, V}, title = {CE-MS-Based Clinical Metabolomics of Human Plasma.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2855}, number = {}, pages = {389-423}, pmid = {39354320}, issn = {1940-6029}, mesh = {Humans ; *Electrophoresis, Capillary/methods ; *Metabolomics/methods ; *Mass Spectrometry/methods ; *COVID-19/blood/diagnosis ; SARS-CoV-2/metabolism ; Plasma/chemistry/metabolism ; }, abstract = {Capillary electrophoresis coupled to mass spectrometry (CE-MS) has emerged as a powerful analytical technique with significant implications for clinical research and diagnostics. The integration of information from CE and MS strengthens confidence in the identification of compounds present in clinical samples. The ability of CE to separate molecules based on their electrophoretic mobility coupled to MS enables the accurate identification and quantification of analytes, even in complex biological matrices such as human plasma.Here, we present a detailed protocol for an untargeted metabolomics study using CE-MS and its application in a study on human plasma from patients suffering Long COVID syndrome. The protocol ranges from sample preparation to biological interpretation, detailing a workflow enabling the analysis of cationic and anionic compounds, metabolite identification, and data processing.}, } @article {pmid39352725, year = {2024}, author = {Hirschtick, JL and Slocum, E and Xie, Y and Power, LE and Elliott, MR and Orellana, RC and Fleischer, NL}, title = {Associations Between Acute COVID-19 Symptom Profiles and Long COVID Prevalence: Population-Based Cross-Sectional Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e55697}, pmid = {39352725}, issn = {2369-2960}, support = {U01 CK000510/CK/NCEZID CDC HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Prevalence ; Middle Aged ; Michigan/epidemiology ; Adult ; *Post-Acute COVID-19 Syndrome ; Aged ; Young Adult ; Adolescent ; Symptom Assessment/statistics & numerical data ; }, abstract = {BACKGROUND: Growing evidence suggests that severe acute COVID-19 illness increases the risk of long COVID (also known as post-COVID-19 condition). However, few studies have examined associations between acute symptoms and long COVID onset.

OBJECTIVE: This study aimed to examine associations between acute COVID-19 symptom profiles and long COVID prevalence using a population-based sample.

METHODS: We used a dual mode (phone and web-based) population-based probability survey of adults with polymerase chain reaction-confirmed SARS-CoV-2 between June 2020 and May 2022 in the Michigan Disease Surveillance System to examine (1) how acute COVID-19 symptoms cluster together using latent class analysis, (2) sociodemographic and clinical predictors of symptom clusters using multinomial logistic regression accounting for classification uncertainties, and (3) associations between symptom clusters and long COVID prevalence using modified Poisson regression.

RESULTS: In our sample (n=4169), 15.9% (n=693) had long COVID, defined as new or worsening symptoms at least 90 days post SARS-CoV-2 infection. We identified 6 acute COVID-19 symptom clusters resulting from the latent class analysis, with flu-like symptoms (24.7%) and fever (23.6%) being the most prevalent in our sample, followed by nasal congestion (16.4%), multi-symptomatic (14.5%), predominance of fatigue (10.8%), and predominance of shortness of breath (10%) clusters. Long COVID prevalence was highest in the multi-symptomatic (39.7%) and predominance of shortness of breath (22.4%) clusters, followed by the flu-like symptom (15.8%), predominance of fatigue (14.5%), fever (6.4%), and nasal congestion (5.6%) clusters. After adjustment, females (vs males) had greater odds of membership in the multi-symptomatic, flu-like symptom, and predominance of fatigue clusters, while adults who were Hispanic or another race or ethnicity (vs non-Hispanic White) had greater odds of membership in the multi-symptomatic cluster. Compared with the nasal congestion cluster, the multi-symptomatic cluster had the highest prevalence of long COVID (adjusted prevalence ratio [aPR] 6.1, 95% CI 4.3-8.7), followed by the predominance of shortness of breath (aPR 3.7, 95% CI 2.5-5.5), flu-like symptom (aPR 2.8, 95% CI 1.9-4.0), and predominance of fatigue (aPR 2.2, 95% CI 1.5-3.3) clusters.

CONCLUSIONS: Researchers and clinicians should consider acute COVID-19 symptom profiles when evaluating subsequent risk of long COVID, including potential mechanistic pathways in a research context, and proactively screen high-risk patients during the provision of clinical care.}, } @article {pmid39352145, year = {2025}, author = {Buonsenso, D and Camporesi, A and Di Sante, G and Sali, M and Boza, MDCP and Morello, R and Valentini, P and Raffaelli, F and Rodriguez, L and Gonzalez, L and Johnsson, A and Mugabo, CH and Lakshmikanth, T and Brodin, P}, title = {Cytokine Profile in Children Following SARS-CoV-2 Infection: Preliminary Findings.}, journal = {The Pediatric infectious disease journal}, volume = {44}, number = {1}, pages = {54-57}, pmid = {39352145}, issn = {1532-0987}, mesh = {Humans ; *COVID-19/immunology/blood ; Child ; Female ; Male ; *Cytokines/blood ; *SARS-CoV-2/immunology ; Adolescent ; Child, Preschool ; }, abstract = {We provide preliminary evidence that, also in children, Long coronavirus disease (COVID) may be characterized by a proinflammatory signature. Ten Long COVID patients, 7 convalescent subjects after COVID infection and 4 healthy controls were enrolled. When adjusted for sex, children with long COVID had statistically significant differences in the levels of Flt3L, CD5, uPA, CCL23, CD40 and TGFα. When adjusted for age, CCL23 levels remained statistically significant.}, } @article {pmid39351379, year = {2024}, author = {Leavy, OC and Russell, RJ and Harrison, EM and Lone, NI and Kerr, S and Docherty, AB and Sheikh, A and Richardson, M and Elneima, O and Greening, NJ and Harris, VC and Houchen-Wolloff, L and McAuley, HJC and Saunders, RM and Sereno, M and Shikotra, A and Singapuri, A and Aul, R and Beirne, P and Bolton, CE and Brown, JS and Choudhury, G and Diar Bakerly, N and Easom, N and Echevarria, C and Fuld, J and Hart, N and Hurst, JR and Jones, M and Parekh, D and Pfeffer, P and Rahman, NM and Rowland-Jones, S and Shah, AM and Wootton, DG and Jolley, C and Thompson, AAR and Chalder, T and Davies, MJ and De Soyza, A and Geddes, JR and Greenhalf, W and Heller, S and Howard, L and Jacob, J and Jenkins, RG and Lord, JM and Man, WD and McCann, GP and Neubauer, S and Openshaw, PJM and Porter, J and Rowland, MJ and Scott, JT and Semple, MG and Singh, SJ and Thomas, D and Toshner, M and Lewis, K and Heaney, LG and Briggs, A and Zheng, B and Thorpe, M and Quint, JK and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Raman, B and Wain, LV and Brightling, CE and Evans, RA}, title = {1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.}, journal = {ERJ open research}, volume = {10}, number = {5}, pages = {}, pmid = {39351379}, issn = {2312-0541}, abstract = {BACKGROUND: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge.

METHODS: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias.

FINDINGS: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups.

INTERPRETATION: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.}, } @article {pmid39350480, year = {2025}, author = {Chuang, YC and Cheng, YH and Tsai, MJ and Lu, YJ and Fuh, JL}, title = {The neuropsychological impacts of coronavirus disease 2019 in nonhospitalized patients with long coronavirus disease and brain fog.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {88}, number = {1}, pages = {58-64}, doi = {10.1097/JCMA.0000000000001175}, pmid = {39350480}, issn = {1728-7731}, mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; *Neuropsychological Tests ; Adult ; Cognitive Dysfunction/etiology ; SARS-CoV-2 ; Executive Function ; Cognition ; Aged ; Brain ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) causes persistent symptoms, including brain fog. Based on limited research on the long-term consequences of mild COVID-19, which has yielded inconsistent results, we investigated which cognitive functions were most affected by COVID-19 in nonhospitalized Asian patients with long-term COVID and subjective cognitive complaints.

METHODS: Fifty-five nonhospitalized patients with subjective cognitive complaints after COVID infection (24 males and 31 females, mean age: 45.6 ± 14.6 years, mean duration of education: 14.4 ± 3.0 years) finished the study. Neuropsychological assessments included screening tests for overall cognition, and comprehensive tests for memory, executive function, processing speed, and subjective emotional and disease symptoms. Cognitive test scores were converted into Z -scores. Moreover, principal component analysis (PCA) was used to define cognitive domains across subtest scores.

RESULTS: Comprehensive assessments revealed cognitive impairment in 69.1% of patients (<1.5 SD in at least one test). The processing speed (27.3%), memory recall (21.8%), memory learning (20.0%), and inhibitory control (18.2%) were the most affected areas. Self-reported anxiety and depression were observed in 35% and 33% of patients, respectively. Furthermore, the degree of anxiety was predictive of learning performance.

CONCLUSION: Nearly 70% of patients with subjective cognitive complaints and long COVID had objective cognitive impairments. A comprehensive evaluation is essential for these patients, even when they present with mild symptoms.}, } @article {pmid39350082, year = {2024}, author = {Sarani, M and Motamed, N and Hatami, G and Namvar, A and Ravanipour, M}, title = {Long COVID in children and adolescents: a historical cohort study with a population-based control group from Iran.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1074}, pmid = {39350082}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Iran/epidemiology ; Female ; Child ; Adolescent ; *SARS-CoV-2 ; Cohort Studies ; Hospitalization/statistics & numerical data ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Child, Preschool ; Pandemics ; Fatigue/epidemiology ; }, abstract = {BACKGROUND: After recovering from the acute phase of COVID-19, some of the infected children manifest long COVID symptoms. The present study aims to identify long COVID symptoms in children and adolescents admitted to hospitals in Bushehr, Iran, during 2021 to 2023, and compare them with the non-affected group.

METHODS: This historical cohort study with a population-based control group was conducted on 141 children and adolescents with COVID-19 hospitalized in Bushehr city hospitals and 141 non-affected peers. Out of 10 comprehensive health service centers in Bushehr city, 5 centers were selected by random sampling and the non-Covid-19 group was chosen from them (matched by gender and age with the affected group). The data were collected using the data recorded in the patients' records, conducting telephone interviews and completing the prevalent long COVID symptom form. Data were analyzed using SPSS version 18. Descriptive statistics, Chi-square/Fisher's exact tests, and stepwise logistic regression were used. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with p < 0.05 as the significance level.

RESULTS: The mean age of the hospitalized children with COVID-19 was 79 ± 5.24 months old, 57.4% of whom were boys. Also, 46 individuals of the COVID-19 group (32.6%) manifested long COVID symptoms. The most prevalent symptoms included fatigue (54.3%), impaired attention or concentration (41.3%) and depression or anxiety symptoms (34.7%). Among the hospitalized children experiencing long-term COVID symptoms, 65.2% exhibited moderate disease severity. A significant relationship was identified between disease severity and muscle and joint pain (P = 0.025), as well as between the length of hospital stay and cough (P = 0.022), weight loss (P = 0.047), and symptoms of depression or anxiety (P = 0.008). Older age [(6-11 y; OR = 3.18, CI = 1.03-9.88); (12 ≥ y; OR = 4.57, CI = 1.40-14.96)] and having history of smoking or being exposed to secondhand smoke (OR = 12.45, CI = 3.14-49.36) were considered as risk factors for long COVID.

CONCLUSIONS: The variables of age and history of exposure to tobacco smoke exhibited a significant independent relationship with the occurrence of long-term COVID symptoms in children hospitalized due to COVID-19. Specifically, as age increases and the history of tobacco smoke exposure rises, the likelihood of experiencing long-term COVID symptoms also increases.}, } @article {pmid39349924, year = {2024}, author = {Nuber-Champier, A and Breville, G and Voruz, P and Jacot de Alcântara, I and Cionca, A and Allali, G and Lalive, PH and Benzakour, L and Lövblad, KO and Braillard, O and Nehme, M and Coen, M and Serratrice, J and Reny, JL and Pugin, J and Guessous, I and Landis, BN and Assal, F and Péron, JA}, title = {Systemic cytokines related to memory function 6-9 months and 12-15 months after SARS-CoV-2 infection.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22660}, pmid = {39349924}, issn = {2045-2322}, support = {220041/WT_/Wellcome Trust/United Kingdom ; 220041/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/blood/immunology ; Middle Aged ; Male ; Female ; Aged ; Adult ; *SARS-CoV-2 ; *Cytokines/blood ; *Interleukin-1beta/blood ; Interleukin-6/blood ; Memory, Episodic ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {Cognitive symptoms persisting beyond the acute phase of COVID-19 infection are commonly described for up to 2 years after infection. The relationship between cognitive performance, in particular episodic memory processes observed chronically after infection, and cytokine levels in the acute phase of COVID-19 has not yet been identified in humans. To determine whether the levels of cytokines IL1β, IL-6 and TNFα secreted in the acute phase of SARS-CoV-2 infection are associated and predict verbal and visuospatial episodic memory performance in humans 6 to 9 months and 12 to 15 months post-infection. The associations and predictive value of the concentration of cytokines measured in acute phase (IL-1β, IL-6, TNFα) from plasma samples of N = 33 hospitalized COVID-19 patients (mean age 61 years, 39-78, 65% in intensive care) in relation to their verbal and visuospatial episodic memory performance measured at 6-9 months and 12-15 months post-infection were analyzed. To do this, we used Spearman correlations and generalised linear mixed models. IL-1β levels were associated with verbal episodic memory total recall scores 6-9 months post-infection. At 12-15 months post-infection IL-6 predicted verbal episodic memory score. This study demonstrated that the severity of inflammatory reaction at acute phase of SARS-CoV-2 infection predicts verbal episodic memory performance in the long-term post-infection.}, } @article {pmid39349781, year = {2024}, author = {Zubchenko, S and Havrylyuk, A and Kril, I and Nadishko, O and Kolinkovskyi, O and Chopyak, V}, title = {Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).}, journal = {Rheumatology international}, volume = {44}, number = {12}, pages = {2873-2883}, pmid = {39349781}, issn = {1437-160X}, mesh = {Humans ; *Herpesvirus 6, Human/immunology ; Male ; Female ; *COVID-19/immunology ; *Killer Cells, Natural/immunology ; Middle Aged ; Adult ; Pilot Projects ; Aged ; Young Adult ; SARS-CoV-2/immunology ; Fas Ligand Protein/blood ; Adolescent ; Roseolovirus Infections/immunology ; }, abstract = {Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65 years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.}, } @article {pmid39349557, year = {2024}, author = {Zhu, S and McCullough, K and Pry, JM and Jain, S and White, LA and León, TM}, title = {Modeling the burden of long COVID in California with quality adjusted life-years (QALYS).}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22663}, pmid = {39349557}, issn = {2045-2322}, support = {U01 CK000539/CK/NCEZID CDC HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; California/epidemiology ; *Quality-Adjusted Life Years ; Adolescent ; Adult ; Middle Aged ; Aged ; Child ; Child, Preschool ; Young Adult ; Infant ; *SARS-CoV-2/isolation & purification ; Male ; Female ; Severity of Illness Index ; Infant, Newborn ; Cost of Illness ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; }, abstract = {Individuals infected with SARS-CoV-2 may develop post-acute sequelae of COVID-19 ("long COVID") even after asymptomatic or mild acute illness. Including time varying COVID symptom severity can provide more informative burden estimates for public health response. Using a compartmental model driven by confirmed cases, this study estimated long COVID burden by age group (0-4, 5-17, 18-49, 50-64, 65+) in California as measured by the cumulative and severity-specific proportion of quality-adjusted life years (QALYs) lost. Long COVID symptoms were grouped into severe, moderate, and mild categories based on estimates from the Global Burden of Disease study, and symptoms were assumed to decrease in severity in the model before full recovery. All 10,945,079 confirmed COVID-19 cases reported to the California Department of Public Health between March 1, 2020, and December 31, 2022, were included in the analysis. Most estimated long COVID-specific QALYs [59,514 (range: 10,372-180,257)] lost in California were concentrated in adults 18-49 (31,592; 53.1%). Relative to other age groups, older adults (65+) lost proportionally more QALYs from severe long COVID (1,366/6,984; 20%). Due to changing case ascertainment over time, this analysis might underestimate the actual total burden. In global sensitivity analysis, estimates of QALYs lost were most sensitive to the proportion of individuals that developed long COVID and proportion of cases with each initial level of long COVID symptom severity (mild/moderate/severe). Models like this analysis can help translate observable metrics such as cases and hospitalizations into quantitative estimates of long COVID burden that are currently difficult to directly measure. Unlike the observed relationship between age and incident severe outcomes for COVID-19, this study points to the potential cumulative impact of mild long COVID symptoms in younger individuals.}, } @article {pmid39349473, year = {2024}, author = {Chapman, M and Durbaba, S and Tydeman, F and Friend, M and Duly, L and Moore, J and Curcin, V and Wang, Y and Jolley, CJ and Kaltsakas, G and Chalder, T and Hart, N and Ashworth, M}, title = {Long COVID demographic and secondary care referral characteristics in primary care: analysis of anonymised primary care data from a multiethnic, deprived urban area in the UK.}, journal = {NPJ primary care respiratory medicine}, volume = {34}, number = {1}, pages = {25}, pmid = {39349473}, issn = {2055-1010}, support = {COV210802//NHS Charities Together and Guy's and St Thomas' Charity/ ; COV210802//NHS Charities Together and Guy's and St Thomas' Charity/ ; COV210802//NHS Charities Together and Guy's and St Thomas' Charity/ ; NIHR203988//UK Research and Innovation: 'MELD-B'/ ; MR/X009742//Medical Research Council: 'Born in South London (eLIXIR)'/ ; EDDPGM-May22\100002//CRUK: 'CANDETECT'/ ; }, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age Factors ; Comorbidity ; Ethnicity/statistics & numerical data ; *Primary Health Care/statistics & numerical data ; *Referral and Consultation/statistics & numerical data ; *Secondary Care/statistics & numerical data ; United Kingdom/epidemiology ; Urban Population ; *Post-Acute COVID-19 Syndrome/epidemiology/therapy ; }, abstract = {Once the nature and number of patients with Long COVID was more fully understood, UK secondary care developed services to investigate, treat and support these patients. We aimed to identify evidence for demographic health inequalities based on general practitioner (GP) Long COVID referrals to available secondary care services. Despite Long COVID demographics broadly reflecting the multiethnic and socially disadvantaged profile of the study population, we found that secondary care referral was mainly focussed on older age patients and those born in the UK with co-morbid anxiety; although co-morbid diabetes was associated with reduced referrals.}, } @article {pmid39348850, year = {2024}, author = {Kruger, A and Joffe, D and Lloyd-Jones, G and Khan, MA and Šalamon, Š and Laubscher, GJ and Putrino, D and Kell, DB and Pretorius, E}, title = {Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.}, journal = {Seminars in thrombosis and hemostasis}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0044-1790603}, pmid = {39348850}, issn = {1098-9064}, abstract = {Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.}, } @article {pmid39348500, year = {2024}, author = {Rahemtoola, SA and Rahemtoola, MS}, title = {In Reply: Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study.}, journal = {The Pediatric infectious disease journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/INF.0000000000004559}, pmid = {39348500}, issn = {1532-0987}, } @article {pmid39348452, year = {2024}, author = {Ueland, GÅ and Ernes, T and Madsen, TV and Sandberg, S and Åsvold, BO and Løvaas, KF and Cooper, JG}, title = {Women Suffered More Than Men Both During and After the COVID-19 Pandemic-A Cross-Sectional Study Among 29,079 Patients With Type 2 Diabetes.}, journal = {Endocrinology, diabetes & metabolism}, volume = {7}, number = {6}, pages = {e70004}, pmid = {39348452}, issn = {2398-9238}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Diabetes Mellitus, Type 2/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Aged ; Norway/epidemiology ; Sex Factors ; Surveys and Questionnaires ; SARS-CoV-2 ; Adult ; Pandemics ; Depression/epidemiology/etiology ; Registries ; Anxiety/epidemiology/etiology ; Comorbidity ; COVID-19 Vaccines/administration & dosage ; }, abstract = {OBJECTIVE: To investigate the gender differences and the disparities between infected and noninfected patients with type 2 diabetes (T2D) regarding patient-reported experiences during the COVID-19 pandemic in Norway.

METHOD: Register study using questionnaires sent electronically to patients with T2D, June 2022. The questionnaire included 82 questions covering COVID-19 disease, symptoms, medications, comorbidities, hospital care, possibility of working from home and information received from health authorities. Clinical and demographic data were collected from the Norwegian diabetes registry for adults.

RESULTS: A total of 29,079 T2D patients participated, of whom 38.1% were women. Patients infected with COVID-19 were younger, had shorter diabetes duration and less comorbidities than noninfected (p < 0.01). Women reported significantly more anxiety, depression and fear of not getting their diabetes medication than men did. Most patients were vaccinated against COVID-19 (98.3%), whereas approximately 60% had received seasonal flu vaccine, and only 27.2% the pneumococcal vaccine. Women described more vaccine adverse effects and long Covid symptoms. Overall, 14% experienced vaccine complications and 27.3% of infected individuals reported long Covid symptoms. 2.4% of the infected patients needed hospital admission. Patients were satisfied with the follow-up of their diabetes, and with information from the government during the pandemic.

CONCLUSION: Female patients were more likely to experience a prolonged Covid course, and higher degree of adverse effects from the COVID-19 vaccine than male patients. Also, long Covid symptoms were significantly more often reported among female patients, while men were more prone to be hospitalised when infected. Hospitalised patients, both men and women, had significantly higher HbA1C than those who were not hospitalised. T2D patients had a surprisingly low pneumococcal vaccination coverage, despite recommendations in national guidelines.}, } @article {pmid39346769, year = {2024}, author = {Dacosta-Aguayo, R and Torán-Monserrat, P and Carmona-Cervelló, M and León-Gómez, BB and Mataró, M and Puig, J and Monté-Rubio, G and López-Lifante, VM and Maria Manresa-Domínguez, J and Zamora-Putin, V and Montero-Alia, P and Chacón, C and Bielsa-Pascual, J and Moreno-Gabriel, E and García-Sierra, R and Rodríguez-Pérez, MC and Costa-Garrido, A and Prado, JG and Martínez-Cáceres, E and Mateu, L and Massanella, M and Violán, C and Lamonja-Vicente, N}, title = {Multimodal neuroimaging in Long-COVID and its correlates with cognition 1.8 years after SARS-CoV-2 infection: a cross-sectional study of the Aliança ProHEpiC-19 Cognitiu.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1426881}, pmid = {39346769}, issn = {1664-2295}, abstract = {INTRODUCTION: There is a growing interest in the effect of Long-COVID (LC) on cognition, and neuroimaging allows us to gain insight into the structural and functional changes underlying cognitive impairment in LC. We used multimodal neuroimaging data in combination with neuropsychological evaluations to study cognitive complaints in a cohort of LC patients with mild to moderate severity symptoms.

METHODS: We conducted a 3T brain magnetic resonance imaging (MRI) study with diffusion tensor imaging (DTI) and functional MRI (fMRI) sequences on 53 LC patients 1.8 years after acute COVID-19 onset. We administered neuropsychological tests to evaluate cognitive domains and examined correlations with Tract-Based Spatial Statistics (TBSS) and resting state.

RESULTS: We included 53 participants with LC (mean age, 48.23 years; 88.7% females). According to the Frascati criteria, more than half of the participants had deficits in the executive (59%) and attentional (55%) domains, while 40% had impairments in the memory domain. Only one participant (1.89%) showed problems in the visuospatial and visuoconstructive domain. We observed that increased radial diffusivity in different white matter tracts was negatively correlated with the memory domain. Our results showed that higher resting state activity in the fronto-parietal network was associated with lower memory performance. Moreover, we detected increased functional connectivity among the bilateral hippocampus, the right hippocampus and the left amygdala, and the right hippocampus and the left middle temporal gyrus. These connectivity patterns were inversely related to memory and did not survive false discovery rate (FDR) correction.

DISCUSSION: People with LC exhibit cognitive impairments linked to long-lasting changes in brain structure and function, which justify the cognitive alterations detected.}, } @article {pmid39345344, year = {2024}, author = {Bellis, RT and Cooper, F and Knoeff, R and McGuire, C and Parry, M and Tybjerg, K and Verwaal, RE and Woods, A}, title = {History at the heart of medicine.}, journal = {Wellcome open research}, volume = {9}, number = {}, pages = {249}, pmid = {39345344}, issn = {2398-502X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {With a focus on the challenges of today and tomorrow in the critical medical humanities the role of history is often overlooked. Yet history and medicine are closely intertwined. Right now, with the surfacing of knotty problems such as changing demographics, chronic pain, loneliness and Long Covid - and the consequent necessity to change directions and policies - history seems more urgent than ever. However, historians of medicine have sometimes been reticent to play a role in medicine and policymaking. The recent and welcome development of the critical medical humanities has intervened in medicine in important ways, but often without clear engagement with the history of medicine. In this letter, we make a renewed case for coherence and collaboration between history of medicine, medicine, and medical humanities, emphasising the continuity and links between all three. The skills and focus of the historian of medicine bring crucial historical context to the table, enabling better understanding of medical collecting, new imaginative futures, profound critiques of key medical concepts, and understandings of the body through time. By emphasising what historians can do for medicine and medical humanities, we call for building historical work into how medicine, illness and health are understood now and in the future. We suggest three potential roles for historians: keepers of memories, conversation partners, and futurist thinkers.}, } @article {pmid39345136, year = {2024}, author = {Zhang, C and Gerzanich, V and Cruz-Cosme, R and Zhang, J and Tsymbalyuk, O and Tosun, C and Sallapalli, BT and Liu, D and Keledjian, K and Papadimitriou, JC and Drachenberg, CB and Nasr, M and Zhang, Y and Tang, Q and Simard, JM and Zhao, RY}, title = {SARS-CoV-2 ORF3a induces COVID-19-associated kidney injury through HMGB1-mediated cytokine production.}, journal = {mBio}, volume = {15}, number = {11}, pages = {e0230824}, pmid = {39345136}, issn = {2150-7511}, support = {R01NS102589, R01NS105633//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; I01BX004652//U.S. Department of Veterans Affairs (VA)/ ; SC170199//U.S. Department of Defense (DOD)/ ; G12MD007597//HHS | NIH | National Institute on Minority Health and Health Disparities (NIMHD)/ ; R01 NS105633/NS/NINDS NIH HHS/United States ; I01 BX004652/BX/BLRD VA/United States ; SC1AI112785//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; I01RX003060 ,I01BX004652//U.S. Department of Veterans Affairs (VA)/ ; R01 NS107262/NS/NINDS NIH HHS/United States ; R01 NS102589/NS/NINDS NIH HHS/United States ; I01 RX003060/RX/RRD VA/United States ; G12 MD007597/MD/NIMHD NIH HHS/United States ; R01NS107262//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21 AI175931/AI/NIAID NIH HHS/United States ; R01HL082517//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01 HL082517/HL/NHLBI NIH HHS/United States ; R21AI175931//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; SC1 AI112785/AI/NIAID NIH HHS/United States ; }, mesh = {*HMGB1 Protein/metabolism/genetics ; *COVID-19/complications/metabolism/virology ; Animals ; Humans ; Mice ; *SARS-CoV-2/genetics ; *Cytokines/metabolism ; *Viroporin Proteins/genetics/metabolism ; Acute Kidney Injury/metabolism/virology/genetics ; Kidney/pathology/virology/metabolism ; Apoptosis ; Epithelial Cells/virology/metabolism ; Mice, Inbred C57BL ; Male ; }, abstract = {UNLABELLED: The primary challenge posed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19-related mortality, often exacerbated by additional medical complications, such as COVID-19-associated kidney injuries (CAKIs). Up to half of COVID-19 patients experience kidney complications, with those facing acute respiratory failure and kidney injury having the worst overall prognosis. Despite the significant impact of CAKI on COVID-19-related mortality and its enduring effects in long COVID, the underlying causes and molecular mechanisms of CAKI remain elusive. In this study, we identified a functional relationship between the expression of the SARS-CoV-2 ORF3a protein and inflammation-driven apoptotic death of renal tubular epithelial cells in patients with CAKI. We demonstrate in vitro that ORF3a independently induces renal cell-specific apoptotic cell death, as evidenced by the elevation of kidney injury molecule-1 (KIM-1) and the activation of NF-kB-mediated proinflammatory cytokine (TNFα and IL-6) production. By examining kidney tissues of SARS-CoV-2-infected K18-ACE2 transgenic mice, we observed a similar correlation between ORF3a-induced cytopathic changes and kidney injury. This correlation was further validated through reconstitution of the ORF3a effects via direct adenoviral injection into mouse kidneys. Through medicinal analysis, we identified a natural compound, glycyrrhizin (GL4419), which not only blocks viral replication in renal cells, but also mitigates ORF3a-induced renal cell death by inhibiting activation of a high mobility group box 1 (HMGB1) protein, leading to a reduction of KIM-1. Moreover, ORF3a interacts with HMGB1. Overproduction or downregulation of hmgb1 expression results in correlative changes in renal cellular KIM-1 response and respective cytokine production, implicating a crucial role of HMGB1 in ORF3a-inflicted kidney injuries. Our data suggest a direct functional link between ORF3a and kidney injury, highlighting ORF3a as a unique therapeutic target contributing to CAKI.

IMPORTANCE: The major challenge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the pandemic is COVID-19-related mortality, which has tragically claimed millions of lives. COVID-19-associated morbidity and mortality are often exacerbated by pre-existing medical conditions, such as chronic kidney diseases (CKDs), or the development of acute kidney injury (AKI) due to COVID-19, collectively known as COVID-19-associated kidney injuries (CAKIs). Patients who experience acute respiratory failure with CAKI have the poorest clinical outcomes, including increased mortality. Despite these alarming clinical findings, there is a critical gap in our understanding of the underlying causes of CAKI. Our study establishes a direct correlation between the expression of the SARS-CoV-2 viral ORF3a protein and kidney injury induced by ORF3a linking to CAKI. This functional relationship was initially observed in our clinical studies of COVID-19 patients with AKI and was further validated through animal and in vitro cellular studies, either by expressing ORF3a alone or in the context of viral infection. By elucidating this functional relationship and its underlying mechanistic pathways, our research deepens the understanding of COVID-19-associated kidney diseases and presents potential therapeutic avenues to address the healthcare challenges faced by individuals with underlying conditions.}, } @article {pmid39343334, year = {2024}, author = {Bilc, M and Cramer, H}, title = {Use of Complementary Medicine Among US Adults with Post-COVID-19: Results from the 2022 National Health Interview Survey.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.09.023}, pmid = {39343334}, issn = {1555-7162}, abstract = {OBJECTIVE: The aim of this study was to investigate the prevalence and type of complementary medicine (CM) use as well as potential factors related to CM use in a representative sample of US adults with self-reported post-COVID-19.

METHODS: This secondary data analysis was based on data from the 2022 National Health Interview Survey 2022 about presence of post-COVID-19 symptoms and CM use in a representative adult sample (weighted n = 89,437,918).

RESULTS: Our estimates indicate that 19.7% of those who reported having a symptomatic SARS-CoV-2 infection experienced post-COVID-19 symptoms, and 46.2% of those reported using any type of CM in the last 12 months. Specifically, post-COVID-19 respondents most often used mind-body medicine (32.0%), followed by massage (16.1%), chiropractic (14.4%), acupuncture (3.4%), naturopathy (2.2%), and art or music therapy (2.1%). Reporting post-COVID-19 was associated with an increased likelihood of using any CM in the last 12 months (adjusted odds ratio [AOR] 1.18; 95% confidence interval [CI]. 1.03-1.34; P = .014) and specifically, to visit an art or music therapist (AOR 2.56; 95% CI, 1.58-4.41; P < .001). The overall use of any CM was more likely among post-COVID-19 respondents under 65 years old, females, those with an ethnic background other than Hispanic, African-American, Asian, or non-Hispanic Whites, having a higher educational level, living in large metropolitan areas, and having private health insurance.

CONCLUSIONS: Our findings show a high prevalence of CM use among post-COVID-19 respondents, which highlights the need for further investigations on effectiveness, safety, and possible mechanisms of action.}, } @article {pmid39342666, year = {2024}, author = {Matsuyama, E and Miyata, J and Terai, H and Miyazaki, N and Iwasaki, T and Nagashima, K and Watase, M and Sunata, K and Namkoong, H and Asakura, T and Masaki, K and Chubachi, S and Ohgino, K and Kawada, I and Minami, K and Hagiwara, R and Ueda, S and Yoshiyama, T and Kokuto, H and Kusumoto, T and Oashi, A and Miyawaki, M and Saito, F and Tani, T and Ishioka, K and Takahashi, S and Nakamura, M and Ishii, M and Sato, Y and Fukunaga, K}, title = {Chronic obstructive pulmonary disease, asthma, and mechanical ventilation are risk factors for dyspnea in patients with long COVID: A Japanese nationwide cohort study.}, journal = {Respiratory investigation}, volume = {62}, number = {6}, pages = {1094-1101}, doi = {10.1016/j.resinv.2024.09.009}, pmid = {39342666}, issn = {2212-5353}, mesh = {Humans ; *Dyspnea/etiology ; *COVID-19/complications ; Risk Factors ; Japan/epidemiology ; *Pulmonary Disease, Chronic Obstructive/complications/therapy ; Male ; Female ; *Respiration, Artificial ; Aged ; *Asthma/complications/therapy/epidemiology ; Middle Aged ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; Adult ; Time Factors ; East Asian People ; }, abstract = {BACKGROUND: Patients often experience multiple prolonged symptoms following acute coronavirus disease 2019 (COVID-19) recovery, defined as long coronavirus disease (COVID). Patients with long COVID may experience dyspnea during acute and post-acute phases. Therefore, this study aimed to identify specific risk factors for dyspnea in patients with long COVID.

METHODS: Hospitalized patients with COVID-19, aged ≥18 years, were enrolled in this multicenter cohort study conducted at 26 medical institutions across Japan. Clinical data during hospitalization and patient-reported outcomes after discharge at the 3, 6, and 12-month follow-ups were retrieved from medical records and paper-based or smartphone application-based questionnaires, respectively.

RESULTS: Generalized linear mixed model (GLMM) analysis of prolonged dyspnea at each time point during follow-up showed that this symptom was associated with chronic obstructive pulmonary disease (COPD) (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.31-5.74), asthma (OR, 2.21; 95%CI, 1.17-4.16), and ventilator management (OR, 3.10; 95%CI, 1.65-5.83). In addition, patients with COPD (44.4%) and ventilator management (25.0%) were more frequently associated with delayed dyspnea onset. The generalized estimating equations analysis results with multiple imputed datasets, conducted as a sensitivity analysis, confirmed the adjusted GLMM analysis results.

CONCLUSIONS: Prolonged dyspnea was associated with COPD, asthma, and severe infection that required mechanical ventilation in the Japanese population with long COVID. Further investigation is needed to clarify its mechanism and develop prophylactic and therapeutic strategies for dyspnea in patients with long COVID.}, } @article {pmid39340624, year = {2024}, author = {Masala, C and Porcu, M and Orofino, G and Defazio, G and Pinna, I and Solla, P and Ercoli, T and Suri, JS and Spinato, G and Saba, L}, title = {Neuroimaging evaluations of olfactory, gustatory, and neurological deficits in patients with long-term sequelae of COVID-19.}, journal = {Brain imaging and behavior}, volume = {18}, number = {6}, pages = {1480-1490}, pmid = {39340624}, issn = {1931-7565}, mesh = {Humans ; *COVID-19/complications/physiopathology/diagnostic imaging ; Male ; Female ; Adult ; *Magnetic Resonance Imaging/methods ; *Olfaction Disorders/etiology/physiopathology/diagnostic imaging ; Middle Aged ; *Brain/diagnostic imaging/physiopathology ; Anosmia/etiology/physiopathology ; Taste Disorders/etiology/physiopathology ; Smell/physiology ; Neuroimaging/methods ; Olfactory Perception/physiology ; Post-Acute COVID-19 Syndrome ; Sensory Thresholds/physiology ; }, abstract = {The World Health Organization indicated that around 36 million of patients in the European Region showed long COVID associated with olfactory and gustatory deficits. The precise mechanism underlying long COVID clinical manifestations is still debated. The aim of this study was to evaluate potential correlations between odor threshold, odor discrimination, odor identification, and the activation of specific brain areas in patients after COVID-19. Sixty subjects, 27 patients (15 women and 12 men) with long COVID and a mean age of 40.6 ± 13.4 years, were compared to 33 age-matched healthy controls (20 women and 13 men) with a mean age of 40.5 ± 9.8 years. Our data showed that patients with long COVID symptoms exhibited a significant decrease in odor threshold, odor discrimination, odor identification, and their sum TDI score compared to age-matched healthy controls. In addition, our results indicated significant correlations between odor discrimination and the increased activation in the right hemisphere, in the frontal pole, and in the superior frontal gyrus. This study indicated that the resting-state fMRI in combination with the objective evaluation of olfactory and gustatory function may be useful for the evaluation of patients with long COVID associated with anosmia and hyposmia.}, } @article {pmid39339976, year = {2024}, author = {Bai, F and Santoro, A and Hedberg, P and Tavelli, A and De Benedittis, S and de Morais Caporali, JF and Marinho, CC and Leite, AS and Santoro, MM and Ceccherini Silberstein, F and Iannetta, M and Juozapaité, D and Strumiliene, E and Almeida, A and Toscano, C and Ruiz-Quiñones, JA and Mommo, C and Fanti, I and Incardona, F and Cozzi-Lepri, A and Marchetti, G and , }, title = {The Omicron Variant Is Associated with a Reduced Risk of the Post COVID-19 Condition and Its Main Phenotypes Compared to the Wild-Type Virus: Results from the EuCARE-POSTCOVID-19 Study.}, journal = {Viruses}, volume = {16}, number = {9}, pages = {}, pmid = {39339976}, issn = {1999-4915}, support = {European Union´s Horizon Europe Research and Innovation Programme under Grant Agreement No 101046016//Horizon 2020/ ; }, mesh = {Humans ; *COVID-19/virology/epidemiology ; *SARS-CoV-2/genetics/pathogenicity ; Female ; Male ; Middle Aged ; Aged ; *Phenotype ; Adult ; Intensive Care Units ; Post-Acute COVID-19 Syndrome ; Hospitalization/statistics & numerical data ; Risk Factors ; }, abstract = {Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020-June 2023); a subset of participants with ≥1 visit over the year after clinical recovery were analyzed. Variants were observed or estimated using Global Data Science Initiative (GISAID) data. Because patients returning for a post COVID-19 visit may have a higher PCC risk, and because the variant could be associated with the probability of returning, we used weighted logistic regressions. We estimated the proportion of the effect of wild-type (WT) virus vs. Omicron on PCC, which was mediated by Intensive Care Unit (ICU) admission, through a mediation analysis. In total, 1317 patients returned for a post COVID visit at a median of 2.6 (IQR 1.84-3.97) months after clinical recovery. WT was present in 69.6% of participants, followed by the Alpha (14.4%), Delta (8.9%), Gamma (3.9%) and Omicron strains (3.3%). Among patients with PCC, the most common manifestations were fatigue (51.7%), brain fog (32.7%) and respiratory symptoms (37.2%). Omicron vs. WT was associated with a reduced risk of PCC and PCC clusters; conversely, we observed a higher risk with the Delta and Alpha variants vs. WT. In total, 42% of the WT effect vs. Omicron on PCC risk appeared to be mediated by ICU admission. A reduced PCC risk was observed after Omicron infection, suggesting a possible reduction in the PCC burden over time. A non-negligible proportion of the variant effect on PCC risk seems mediated by increased disease severity during the acute disease.}, } @article {pmid39338165, year = {2024}, author = {Man, DE and Andor, M and Buda, V and Kundnani, NR and Duda-Seiman, DM and Craciun, LM and Neagu, MN and Carlogea, IS and Dragan, SR}, title = {Insulin Resistance in Long COVID-19 Syndrome.}, journal = {Journal of personalized medicine}, volume = {14}, number = {9}, pages = {}, pmid = {39338165}, issn = {2075-4426}, abstract = {Background: The COVID-19 pandemic has caused severe health issues worldwide and contributed to huge financial losses. Key comorbidities linked to an increased risk of severe COVID-19 and higher mortality rates include cardio-metabolic disorders such as type 1 and type 2 diabetes mellitus (T1DM and T2DM), atherosclerotic cardiovascular disease, chronic kidney disease, hypertension, heart failure, and obesity. The persistence of symptoms even after the acute phase is over is termed long COVID-19 syndrome. This study aimed to evaluate the relationship between long COVID-19 syndrome and the development of insulin resistance in previously non-diabetic patients. Methods: A prospective observational study was performed on 143 non-diabetic patients who had tested positive for SARS-CoV-2 infection by a PCR test and were hospitalized in our hospital between January 2020 and December 2022. The clinical and para-clinical data at 0, 4, and 12 months of hospital admission for post-COVID-19 infection follow-up was collected and labeled as t0, t4, and t12. Blood glucose, insulin, and C-peptide levels were measured at the beginning and further at 2, 5, 10, and 30 min after the intravenous arginine stimulation test. Similarly, BMI was calculated, and hs-CRP and ESR levels were noted. The results obtained were statistically analyzed. Results: More than one-third (30.7%) of the included patients developed long COVID-19 syndrome. It was found that 75% of patients with long COVID-19 hospitalized in our clinic developed diabetes within a year of acute infection with COVID-19; therefore, it can be said that the presence of long COVID-19 is a major risk for an altered metabolic status, which can cause diabetes. When comparing the glycemia levels (106 mg/dL) with the BMI at t0, t4, and t12 time intervals, the p-values were found to be 0.214, 0.042, and 0.058, respectively. Almost 62% of the patients having BMI > 30 kg/m[2] were found to have an increase in blood glucose levels at 1 year. Similarly, insulin resistance was noted during this interval. A negative correlation of 0.40 for hsCRP and 0.38 for ESR was noted when compared with acute infection with COVID-19. Conclusions: The association between long COVID-19 and insulin resistance highlights the varied and widespread impacts of SARS-CoV-2 infection. Addressing the complexities of long COVID-19 requires a holistic strategy that encompasses both respiratory and metabolic considerations, which is crucial for enhancing the well-being of those enduring this persistent condition.}, } @article {pmid39338088, year = {2024}, author = {Goldhaber, NH and Ramesh, K and Horton, LE and Longhurst, CA and Huang, E and Horgan, S and Jacobsen, GR and Sandler, BJ and Broderick, RC}, title = {The Long Haul to Surgery: Long COVID Has Minimal Burden on Surgical Departments.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {9}, pages = {}, pmid = {39338088}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Surgery Department, Hospital/statistics & numerical data ; Surgical Procedures, Operative/statistics & numerical data ; }, abstract = {Many patients infected with the SARS-CoV-2 virus (COVID-19) continue to experience symptoms for weeks to years as sequelae of the initial infection, referred to as "Long COVID". Although many studies have described the incidence and symptomatology of Long COVID, there are little data reporting the potential burden of Long COVID on surgical departments. A previously constructed database of survey respondents who tested positive for COVID-19 was queried, identifying patients reporting experiencing symptoms consistent with Long COVID. Additional chart review determined whether respondents had a surgical or non-routine invasive procedure on or following the date of survey completion. Outcomes from surgeries on patients reporting Long COVID symptoms were compared to those from asymptomatic patients. A total of 17.4% of respondents had surgery or a non-routine invasive procedure in the study period. A total of 48.8% of these patients reported experiencing symptoms consistent with Long COVID. No statistically significant differences in surgical outcomes were found between groups. The results of this analysis demonstrate that Long COVID does not appear to have created a significant burden of surgical disease processes on the healthcare system despite the wide range of chronic symptoms and increased healthcare utilization by this population. This knowledge can help guide surgical operational resource allocation as a result of the pandemic and its longer-term sequelae.}, } @article {pmid39337879, year = {2024}, author = {Ciobica, ML and Sandulescu, BA and Sotcan, MA and Dumitrescu, LM and Eftimie, LG and Calin, CI and Iordache, M and Cuzino, D and Carsote, M and Nistor, C and Radu, AM}, title = {Superficial Vein Thrombosis in an Asymptomatic Case of Cholangiocarcinoma with Recent History of COVID-19.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39337879}, issn = {2075-1729}, abstract = {The COVID-19 pandemic brought into prominence several emergent medical and surgical entities, but, also, it served as trigger and contributor for numerous apparently unrelated ailments such as arterial and venous thromboembolic complications. Additional risk factors for these thrombotic traits may be concurrent (known or unknown) malignancies, including at hepatic level. Among these, cholangiocarcinoma (CCA), a rare cancer of intra- and extra-hepatic biliary ducts, represents a very aggressive condition that typically associates local and distant advanced stages on first presentation requiring a prompt diagnosis and a stratified management. This neoplasia has been reported to present a large spectrum of paraneoplastic syndromes in terms of dermatologic, renal, systemic, neurologic, endocrine, and cardiovascular settings, that, overall, are exceptional in their epidemiologic impact when compared to other cancers. Our aim was to introduce a most unusual case of CCA-associated distant thrombosis in a male adult who initially was considered to experience COVID-19-related thrombotic features while having a history of obesity and bariatric surgery. This is a hybrid type of paper: this clinical vignette is accompanied by two distinct sample-focused analyses as a basis for discussion; they each had different methods depending on their current level of statistical evidence. We only included English-published articles in PubMed, as follows: Firstly, we conducted a search of reports similar to the present case, regarding distant vein thrombosis in CCA, from inception until the present time. We performed a literature search using the keywords "cholangiocarcinoma", "thrombosis", and "Trousseau's syndrome" and identified 20 cases across 19 original papers; hence, the current level of evidence remains very low Secondly, we searched for the highest level of statistical evidence concerning the diagnosis of venous thrombosis/thromboembolism in patients who underwent COVID-19 infection (key search terms were "COVID-19", alternatively, "coronavirus", and "SARS-CoV-2", and "thrombosis", alternatively, "thromboembolism") and included the most recent systematic reviews and meta-analyses that were published in 2024 (from 1 January 2024 until 8 July 2024). After excluding data on vaccination against coronavirus or long COVID-19 syndrome, we identified six such articles. To conclude, we presented a probably unique case of malignancy with an initial manifestation consisting of recurrent superficial vein thrombosis under anticoagulation therapy, with no gastrointestinal manifestations, in a patient with a notable history for multiple episodes of SARS-CoV-2 infection and a prior endocrine (gastric) surgery. To our knowledge, this is the first identification of a CCA under these specific circumstances.}, } @article {pmid39337860, year = {2024}, author = {Koutsiaris, AG}, title = {A Blood Supply Pathophysiological Microcirculatory Mechanism for Long COVID.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {39337860}, issn = {2075-1729}, abstract = {BACKGROUND: The term "Long COVID" is commonly used to describe persisting symptoms after acute COVID-19. Until now, proposed mechanisms for the explanation of Long COVID have not related quantitative measurements to basic laws. In this work, a common framework for the Long COVID pathophysiological mechanism is presented, based on the blood supply deprivation and the flow diffusion equation.

METHODS: Case-control studies with statistically significant differences between cases (post-COVID patients) and controls, from multiple tissues and geographical areas, were gathered and tabulated. Microvascular loss (ML) was quantified by vessel density reduction (VDR), foveal avascular zone enlargement (FAZE), capillary density reduction (CDR), and percentage of perfused vessel reduction (PPVR). Both ML and hemodynamic decrease (HD) were incorporated in the tissue blood supply reduction (SR) estimation.

RESULTS: ML data were found from 763 post-COVID patients with an average VDR, FAZE, CDR, and PPVR of 16%, 31%, 14%, and 21%, respectively. The average HD from 72 post-COVID patients was 37%. The estimated SR for multiple tissues with data from 634 post-COVID patients reached a sizeable 47%. This large SR creates conditions of lower mass diffusion rates, hypoxia, and undernutrition, which at a multi-tissue level, for a long time, can explain the wide variety of the Long COVID symptoms.

CONCLUSIONS: Disruption of peripheral tissue blood supply by the contribution of both ML and HD is proposed here to be the principal cause of the mechanism leading to Long COVID symptoms.}, } @article {pmid39337465, year = {2024}, author = {Eisenreich, W and Leberfing, J and Rudel, T and Heesemann, J and Goebel, W}, title = {Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337465}, issn = {1422-0067}, support = {EI 384/16 and RU631/17//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *SARS-CoV-2/metabolism/physiology ; *COVID-19/metabolism/virology ; Host-Pathogen Interactions ; Glycolysis ; Virus Replication ; Pentose Phosphate Pathway ; Citric Acid Cycle ; }, abstract = {Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply of nucleotides, amino acids, and lipids since these metabolic products are crucial for efficient viral proliferation. In detail, however, this manipulation may affect multiple sites and regulatory mechanisms of host-cell metabolism, depending not only on the specific viruses but also on the type of infected host cells. In this review, we report metabolic situations and reprogramming in different human host cells, tissues, and organs that are favorable for acute and persistent SARS-CoV-2 infection. This knowledge may be fundamental for the development of host-directed therapies.}, } @article {pmid39337096, year = {2024}, author = {Boccatonda, A and D'Ardes, D and Tallarico, V and Guagnano, MT and Cipollone, F and Schiavone, C and Piscaglia, F and Serra, C}, title = {Role of Lung Ultrasound in the Detection of Lung Sequelae in Post-COVID-19 Patients: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337096}, issn = {2077-0383}, abstract = {Background: During the COVID-19 pandemic, several studies demonstrated the effectiveness of lung ultrasound (LUS) as a frontline tool in diagnosing and managing acute SARS-CoV-2 pneumonia. However, its role in detecting post-COVID-19 lung sequelae remains to be fully determined. This study aims to evaluate the diagnostic accuracy of LUS in identifying lung parenchymal damage, particularly fibrotic-like changes, following COVID-19 pneumonia, comparing its performance to that of CT. Methods: Relevant studies published before July 2024 were identified through a comprehensive search of PubMed, Embase, and Cochrane library. The search terms were combinations of the relevant medical subject heading (MeSH) terms, key words and word variants for "lung", "post-COVID", "long-COVID", and "ultrasound". The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve were used to examine the accuracy of CEUS. The selected works used different thresholds for the detection and counting of B-lines by ultrasound. This led to dividing our analysis into two models, the first based on the lower thresholds for detection of B-lines found in the works, and the second on data obtained using a higher detection threshold. Results: In terms of the diagnostic accuracy of LUS in detecting residual fibrotic-like changes in patients post-COVID-19 infection, a low-threshold model displayed a pooled sensitivity of 0.98 [95% confidence interval (CI): 0.95-0.99] and a pooled specificity of 0.54 (95% CI: 0.49-0.59). The DOR was 44.9 (95% CI: 10.8-187.1). The area under the curve (AUC) of SROC was 0.90. In the second analysis, the model with the higher threshold to detect B-lines showed a pooled sensitivity of 0.90 (95% CI: 0.85-0.94) and a pooled specificity of 0.88 (95% CI: 0.84-0.91). The DOR was 50.4 (95% CI: 15.9-159.3). The AUC of SROC was 0.93. Conclusions: In both analyses (even using the high threshold for the detection of B-lines), excellent sensitivity (98% in model 1 and 90% in model 2) is maintained. The specificity has a significant variation between the two models from 54 (model 1) to 87% (model 2). The model with the highest threshold for the detection of B-lines displayed the best diagnostic accuracy, as confirmed by the AUC values of the SROC (0.93).}, } @article {pmid39337079, year = {2024}, author = {Abbasi, A and Gattoni, C and Iacovino, M and Ferguson, C and Tosolini, J and Singh, A and Soe, KK and Porszasz, J and Lanks, C and Rossiter, HB and Casaburi, R and Stringer, WW}, title = {A Pilot Study on the Effects of Exercise Training on Cardiorespiratory Performance, Quality of Life, and Immunologic Variables in Long COVID.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337079}, issn = {2077-0383}, support = {--N/A//Pulmonary Education and Research Foundation/ ; N/A//UCLA David Geffen School of Medicine (DGSoM) - Ventura County Community Foundation (VCCF) Long COVID 19 Research Award/ ; }, abstract = {Objectives: Fatigue is a prominent feature of long COVID (LC) and may be related to several pathophysiologic mechanisms, including immune hyperstimulation. Aerobic endurance exercise training may be a useful therapy, with appropriate attention to preventing post-exertional malaise. Methods: Fourteen participants completed a pilot study of aerobic exercise training (twenty 1.5 h sessions of over 10 weeks). Cardiorespiratory fitness, 6 min walk distance, quality of life, symptoms, 7-day physical activity, immunophenotype, and inflammatory biomarkers were measured before and after exercise training. Results: The participant characteristics at baseline were as follows: 53.5 ± 11.6 yrs, 53% f, BMI 32.5 ± 8.4, 42% ex-smokers, 15.1 ± 8.8 months since initial COVID-19 infection, low normal pulmonary function testing, V.O2peak 19.3 ± 5.1 mL/kg/min, 87 ± 17% predicted. After exercise training, participants significantly increased their peak work rate (+16 ± 20 W, p = 0.010) and V.O2peak (+1.55 ± 2.4 mL/kg/min, p = 0.030). Patients reported improvements in fatigue severity (-11%), depression (-42%), anxiety (-29%), and dyspnea level (-46%). There were no changes in 6MW distance or physical activity. The circulating number of CD3+, CD4+, CD19+, CD14++CD16, and CD16++CD14+ monocytes and CD56+ cells (assessed with flow cytometry) increased with acute exercise (rest to peak) and was not diminished or augmented by exercise training. Plasma concentrations of TNF-α, IL-6, IL-8, IL-10, INF-γ, and INF-λ were normal at study entry and not affected by training. Conclusions: Aerobic endurance exercise training in individuals with LC delivered beneficial effects on cardiorespiratory fitness, quality of life, anxiety, depression, and fatigue without detrimental effects on immunologic function.}, } @article {pmid39337048, year = {2024}, author = {Onik, G and Knapik, K and Sieroń, K}, title = {Long COVID Cardiopulmonary Symptoms and Health Resort Treatment: A Retrospective Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337048}, issn = {2077-0383}, abstract = {Background/Objectives: Long COVID covers many cardio-pulmonary symptoms, worsening individuals' health status. Health resort treatment applies balneological factors, physical medicine modalities, climate actions, and exercises that may be beneficial for COVID-19 survivors. This study aimed to assess the severity of the cardiopulmonary symptoms in people qualified for health resort treatment and its efficacy in this group of patients. Methods: Medical records of 239 people attending health resort treatment were analysed. A total of 122 people (71 women and 51 men) with a mean age of 64.35 years ± 8.66 years were enrolled in the analysis. The cardiopulmonary symptoms of long COVID were assessed twice: before and after health resort treatment. Results: Persisting COVID-19 symptoms do not differentiate between women and men. Health resort treatment reduces symptoms severity in both sexes. Age does not mediate the efficacy of health resort treatment. Conclusions: The persistent symptoms of COVID-19 are of low intensity in people qualified for health resort treatment and are independent of gender. Health resort treatment effectively mitigates dyspnoea, tightness of chest, and sputum in long COVID patients, so it should be implemented into the standard treatment course for COVID-19 survivors as a continuation of therapy.}, } @article {pmid39335603, year = {2024}, author = {Siwy, J and Keller, F and Banasik, M and Peters, B and Dudoignon, E and Mebazaa, A and Gülmez, D and Spasovski, G and Lazo, MS and Rajzer, MW and Fuławka, Ł and Dzitkowska-Zabielska, M and Mischak, H and Hecking, M and Beige, J and Wendt, R and UriCoV Working Group, }, title = {Mortality Risk and Urinary Proteome Changes in Acute COVID-19 Survivors in the Multinational CRIT-COV-U Study.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335603}, issn = {2227-9059}, support = {25323FSB114//Federal Ministry of Health/ ; 01KU2309//Federal Ministry of Education and Research/ ; 2022-00542//VINNOVA/ ; PerMed/V/162/UriCov/2023//National Centre for Research and Development/ ; I 6464//FWF Austrian Science Fund/ ; ANR-22-PERM-0014//Agence Nationale de la Recherche/ ; I 6471//FWF Austrian Science Fund/ ; }, abstract = {BACKGROUND/OBJECTIVES: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated.

METHODS: Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets.

RESULTS: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death.

CONCLUSIONS: The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.}, } @article {pmid39335578, year = {2024}, author = {Lebbe, A and Aboulwafa, A and Bayraktar, N and Mushannen, B and Ayoub, S and Sarker, S and Abdalla, MN and Mohammed, I and Mushannen, M and Yagan, L and Zakaria, D}, title = {New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335578}, issn = {2227-9059}, abstract = {The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.}, } @article {pmid39335455, year = {2024}, author = {Compeer, B and Neijzen, TR and van Lelyveld, SFL and Martina, BEE and Russell, CA and Goeijenbier, M}, title = {Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC).}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335455}, issn = {2227-9059}, abstract = {The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively. Here, in this review, we offer a virologist's perspective on PASC, highlighting the dynamics of SARS-CoV-2 viral loads, cytokines, and chemokines in different organs of patients across the full clinical spectrum of acute-phase disease. We underline that the probability of severe or critical disease progression correlates with increased viral load levels detected in the upper respiratory tract (URT), lower respiratory tract (LRT), and plasma. Acute-phase viremia is a clear, although not unambiguous, predictor of PASC development. Moreover, both the quantity and diversity of functions of cytokines and chemokines increase with acute-phase disease severity. Specific cytokines remain or become elevated in the PASC phase, although the driving factor of ongoing inflammation found in patients with PASC remains to be investigated. The key findings highlighted in this review contribute to a further understanding of PASC and their differences and overlap with acute disease.}, } @article {pmid39335454, year = {2024}, author = {Khoja, O and Mulvey, M and Astill, S and Tan, AL and Sivan, M}, title = {New-Onset Chronic Musculoskeletal Pain Following COVID-19 Infection Fulfils the Fibromyalgia Clinical Syndrome Criteria: A Preliminary Study.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335454}, issn = {2227-9059}, abstract = {New-onset chronic musculoskeletal (MSK) pain (>3 months duration) is a common symptom of post-COVID-19 syndrome (PCS). This study aimed to characterise new-onset chronic MSK pain in patients with PCS and its overlap with Fibromyalgia Syndrome (FMS). We enrolled patients with new-onset chronic MSK pain post-COVID-19 and assessed the nature of the pain and associated symptoms using the C19-YRS (Yorkshire Rehabilitation Scale). The FMS assessment was conducted as part of a standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria: (1) Widespread Pain Index (WPI) ≥ 7 and symptoms severity (SS) score ≥ 5, or WPI between 3 and 6 and SS score ≥ 9, (2) symptoms consistent for at least 3 months, and (3) no alternative diagnosis. Of the eighteen patients (average age 49.6 (SD 11.8) years; BMI 31.7 (SD 8.6)), twelve were female. The average symptom duration was 27.9 (SD 6.97) months post-infection. Thirteen patients (72.2%) met the FMS criteria, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant quality of life impacts. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions.}, } @article {pmid39334847, year = {2024}, author = {Slama Schwok, A and Henri, J}, title = {Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334847}, issn = {2218-273X}, support = {COVNUCLEOVIR//Sorbonne Université/ ; }, mesh = {Humans ; *COVID-19/therapy/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Inflammation ; }, abstract = {Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include a variety of symptoms, such as fatigue, loss of smell (anosmia), and neurological-cognitive sequelae, such as memory loss, anxiety, brain fog, acute encephalitis, and stroke, collectively called long neuro-COVID-19 (long neuro-COVID). They also include cardiopulmonary sequelae, such as myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, and vascular endothelial dysregulation, and the onset of new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand the mechanisms of the pathophysiologic sequelae, in particular the neurological symptoms. This mini-review presents the main mechanistic hypotheses considered to explain the multiple long neuro-COVID symptoms, namely immune dysregulation and prolonged inflammation, persistent viral reservoirs, vascular and endothelial dysfunction, and the disruption of the neurotransmitter signaling along various paths. We suggest that the nucleoprotein N of SARS-CoV-2 constitutes a "hub" between the virus and the host inflammation, immunity, and neurotransmission.}, } @article {pmid39334765, year = {2024}, author = {Yutani, R and Venketaraman, V and Sheren, N}, title = {Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer's Disease: The Potential Role of a Novel Nano-Compound-The Transdermal Glutathione-Cyclodextrin Complex.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39334765}, issn = {2076-3921}, abstract = {Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants-primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer's disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach.}, } @article {pmid39333538, year = {2024}, author = {Danielle, RCS and Débora, DM and Alessandra, NLP and Alexia, SSZ and Débora, MCR and Elizabel, NV and Felipe, AM and Giulia, MG and Henrique, PR and Karen, RMB and Layane, SB and Leandro, AB and Livia, CM and Raquel, SRT and Lorena, SCA and Lyvia, NRA and Mariana, TR and Matheus, CC and Vinícius, DPV and Yasmin, MG and Iúri, DL}, title = {Correlating COVID-19 severity with biomarker profiles and patient prognosis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22353}, pmid = {39333538}, issn = {2045-2322}, support = {485/2021 - 44770.706.17823.29042021//FUNDAÇÃO DE AMPARO A PESQUISA DO ESPÍRITO SANTO/ ; 485/2021 - 44770.706.17823.29042021//FUNDAÇÃO DE AMPARO A PESQUISA DO ESPÍRITO SANTO/ ; 408777/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 408777/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; *COVID-19/blood ; Female ; Male ; *Biomarkers/blood ; Middle Aged ; *Severity of Illness Index ; Prognosis ; *von Willebrand Factor/metabolism/analysis ; Adult ; Aged ; *SARS-CoV-2/isolation & purification ; Factor VIII/metabolism/analysis ; Fibrin Fibrinogen Degradation Products/analysis/metabolism ; }, abstract = {COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001), MTHFR gene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.}, } @article {pmid39333196, year = {2024}, author = {McMullan, C and Haroon, S and Turner, G and Aiyegbusi, OL and Subramanian, A and Hughes, SE and Flanagan, S and Nirantharakumar, K and Davies, EH and Frost, C and Jackson, L and Guan, N and Alder, Y and Chong, A and Buckland, L and Jeyes, F and Stanton, D and Calvert, M}, title = {Key considerations for digital decentralised clinical trials from a feasibility study assessing pacing interventions for long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22083}, pmid = {39333196}, issn = {2045-2322}, support = {COV-LT-0013//NIHR/ ; }, mesh = {Humans ; *Feasibility Studies ; *COVID-19/therapy/epidemiology ; Post-Acute COVID-19 Syndrome ; Male ; SARS-CoV-2 ; Female ; Middle Aged ; Clinical Trials as Topic ; Aged ; Adult ; Patient Selection ; }, abstract = {Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management. We co-produced a mixed methods feasibility study to evaluate a multi-arm digital decentralised clinical trial (DCT) platform to assess non-pharmacological interventions for Long COVID, using pacing interventions as an exemplar. The study demonstrated that the platform was able to successfully e-consent participants, randomise them into one of four intervention arms, capture baseline data, and capture outcomes relevant to a health economic evaluation. The study also highlighted several challenges, including difficulties with recruitment, imposter participants, and high attrition rates. We highlight how these challenges can potentially be mitigated to make a fully powered DCT more feasible.}, } @article {pmid39332491, year = {2024}, author = {Herring, TE and Chopra, A and Friedly, JL and Bender, JA and Gentile, NL and Knowles, LM}, title = {Post traumatic stress and sleep disorders in long COVID: Patient management and treatment.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123081}, pmid = {39332491}, issn = {1879-0631}, support = {K23 HD111628/HD/NICHD NIH HHS/United States ; U18 HS029905/HS/AHRQ HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/therapy ; *Stress Disorders, Post-Traumatic/therapy/physiopathology ; *Sleep Wake Disorders/therapy ; SARS-CoV-2 ; Risk Factors ; }, abstract = {Post traumatic stress disorder (PTSD) and sleep disorders are prevalent among patients with long COVID. The intersection of PTSD and/or sleep disorders with long COVID is complex. Thus, use of a biopsychosocial lens for assessment and treatment along with a trauma-informed approach to clinical care is recommended. This review provides an overview of the literature on PTSD and sleep disorders among patients with long COVID, including prevalence rates, risk factors, and potential pathophysiology. Pharmacological and non-pharmacological treatment options are reviewed. Also, we provide actionable steps clinicians can integrate into their practice to help effectively assess and treat PTSD and sleep disorders, including validated symptom assessments, recommended referrals, and specific components of non-pharmacological interventions.}, } @article {pmid39329868, year = {2024}, author = {Nica, S and Nica, RI and Nica, HA and Miricescu, D and Abdelfatah, MAAK and Schiopu, OM and Nedelcu, IC and Cimponeriu, DG and Stefani, C and Stanescu-Spinu, II and Ciornei, MC}, title = {Characteristics of Patients with Persistent COVID-19 Symptoms and Unscheduled Return Visits to a Centre for COVID-19 Evaluation.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {39329868}, issn = {2079-9721}, abstract = {Background: This retrospective study aimed to evaluate the characteristics of patients with long COVID syndrome. Methods: This study included 457 adults who had at least one persistent symptom after COVID-19 infection. Results: The median time interval between the last SARS-CoV-2 infection and emergency room presentation was 3 months. Older patients had comorbidities (61.7 vs. 44.9 years, p < 0.0001), moderate or severe forms of COVID-19 (61.2 vs. 50.9 years, p < 0.0001), and respiratory symptoms (56.1 vs. 52.0 years, p = 0.0027). Non-vaccinated patients were older than vaccinated patients (56.0 vs. 51.5 years, p = 0.0008) and had residual lung abnormalities following COVID-19 infection (51.5% vs. 36.8%, p < 0.003). The time interval between the last SARS-CoV-2 infection and the hospital evaluation was shorter for vaccinated patients (3.2 vs. 3.9 months, p < 0.0001) and those with mild forms (3.3 vs. 4.12 months, p = 0.0001) versus non-vaccinated individuals. After the last SARS-CoV-2 infection, 107 patients developed impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus, being patients with already known chronic diseases (p = 0.0002), or hypertension (p = 0.001). Conclusions: Our study pointed out the heterogeneity of symptoms following COVID-19, and they are associated with age, vaccination status, or severity of SARS-CoV-2 infection.}, } @article {pmid39328557, year = {2024}, author = {Kim, TH and Yoon, J and Kim, S and Kang, BK and Kang, JW and Kwon, S}, title = {Herbal medicines for long COVID: A phase 2 pilot clinical study.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37920}, pmid = {39328557}, issn = {2405-8440}, abstract = {BACKGROUND: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction in patients with long COVID.

METHODS: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikgi-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient's symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored.

RESULTS: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80 %, 53.33 %, and 46.67 % in the BIT, KOG, and CBD groups, respectively. However, cognitive dysfunction symptoms showed less improvement, with treatment success rates of 40 %, 46.67 %, and 13.33 % in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence.

CONCLUSIONS: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and cognitive dysfunction.}, } @article {pmid39328154, year = {2024}, author = {Melillo, A and Perrottelli, A and Caporusso, E and Coltorti, A and Giordano, GM and Giuliani, L and Pezzella, P and Bucci, P and Mucci, A and Galderisi, S and Maj, M}, title = {Research evidence on the management of the cognitive impairment component of the post-COVID condition: a qualitative systematic review.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {67}, number = {1}, pages = {e60}, pmid = {39328154}, issn = {1778-3585}, mesh = {Humans ; *Cognitive Dysfunction/therapy/etiology ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; }, abstract = {BACKGROUND: Cognitive impairment (CI) is one of the most prevalent and burdensome consequences of COVID-19 infection, which can persist up to months or even years after remission of the infection. Current guidelines on post-COVID CI are based on available knowledge on treatments used for improving CI in other conditions. The current review aims to provide an updated overview of the existing evidence on the efficacy of treatments for post-COVID CI.

METHODS: A systematic literature search was conducted for studies published up to December 2023 using three databases (PubMed-Scopus-ProQuest). Controlled and noncontrolled trials, cohort studies, case series, and reports testing interventions on subjects with CI following COVID-19 infection were included.

RESULTS: After screening 7790 articles, 29 studies were included. Multidisciplinary approaches, particularly those combining cognitive remediation interventions, physical exercise, and dietary and sleep support, may improve CI and address the different needs of individuals with post-COVID-19 condition. Cognitive remediation interventions can provide a safe, cost-effective option and may be tailored to deficits in specific cognitive domains. Noninvasive brain stimulation techniques and hyperbaric oxygen therapy showed mixed and preliminary results. Evidence for other interventions, including pharmacological ones, remains sparse. Challenges in interpreting existing evidence include heterogeneity in study designs, assessment tools, and recruitment criteria; lack of long-term follow-up; and under-characterization of samples in relation to confounding factors.

CONCLUSIONS: Further research, grounded on shared definitions of the post-COVID condition and on the accurate assessment of COVID-related CI, in well-defined study samples and with longer follow-ups, is crucial to address this significant unmet need.}, } @article {pmid39327301, year = {2024}, author = {Bonnet, U and Kuhn, J}, title = {Antidepressants can help to prevent and manage long COVID depression, anxiety, brain fog and fatigue.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {39327301}, issn = {1433-8491}, } @article {pmid39327264, year = {2024}, author = {Poethko-Müller, C and Schaffrath Rosario, A and Sarganas, G and Ordonez Cruickshank, A and Scheidt-Nave, C and Schlack, R}, title = {[Fatigue in the general population: results of the "German Health Update 2023" study].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {67}, number = {11}, pages = {1208-1221}, pmid = {39327264}, issn = {1437-1588}, mesh = {Humans ; Germany/epidemiology ; Adult ; Male ; Female ; Middle Aged ; *Fatigue/epidemiology ; Aged ; Young Adult ; Adolescent ; Prevalence ; *COVID-19/epidemiology ; Health Surveys ; Risk Factors ; Age Distribution ; SARS-CoV-2 ; Sex Distribution ; }, abstract = {BACKGROUND: Fatigue is an unspecific symptom complex characterized by tiredness, lack of energy, and lack of concentration and is of considerable public health relevance, due to its links with incapacity for work, risk of accidents, and increased need for healthcare.

METHODS: The analyses are based on data from 9766 adults of the telephone survey "Gesundheit in Deutschland aktuell (GEDA)" 2023. Fatigue was recorded using the Fatigue Assessment Scale (FAS), a validated instrument with 10 questions for self-assessment of fatigue. The scale was dichotomized into yes (at least mild to moderate fatigue) versus no (no fatigue). Population-weighted prevalences of fatigue and associated sociodemographic and health-related factors were calculated in descriptive analyses and multivariable Poisson regression.

RESULTS: The overall prevalence of fatigue in adults in Germany is 29.7% (95% CI 28.1-31.2), is highest in 18- to 29-year-olds (39.6% (95% CI 35.0-44.4)), and decreases in the age groups up to 65-79 years (20.6% (95% CI 18.2-23.3)). It is higher again in the very old age group (33.2% (95% CI 28.9-37.7)). Women have a higher risk of fatigue than men (aRR 1.19 (95% CI 1.08-1.32)). Fatigue is significantly associated with age, lower education, chronic illness, depression, and long COVID, regardless of covariates.

DISCUSSION: GEDA 2023 is one of the few population-based studies to have collected data on fatigue. The results allow estimates to be made for Germany on the frequency of fatigue and the significance of physical, psychological, and social influencing factors. They can be used as a reference or as a basis for trends over time as part of continuous health monitoring in Germany.}, } @article {pmid39327204, year = {2024}, author = {Magrini, E and Garlanda, C}, title = {COVID-19 thromboinflammation: adding inflammatory fibrin to the puzzle.}, journal = {Trends in immunology}, volume = {45}, number = {10}, pages = {721-723}, doi = {10.1016/j.it.2024.09.003}, pmid = {39327204}, issn = {1471-4981}, mesh = {*COVID-19/immunology ; Humans ; *Fibrin/metabolism ; Animals ; *SARS-CoV-2/immunology ; *Spike Glycoprotein, Coronavirus/immunology/metabolism ; Thromboinflammation/immunology/metabolism ; Mice ; Fibrinogen/metabolism ; Blood Coagulation ; }, abstract = {Thromboinflammation is a peculiar and key component of acute COVID-19 pathogenesis, which contributes to long COVID. In a recent study, Ryu et al. demonstrate that the SARS-CoV-2 spike protein interacts with fibrinogen, promoting fibrin polymerization and its inflammatory activity. Targeting the inflammatory fibrin peptide protected mice from spike-dependent fibrin clotting and neuropathology.}, } @article {pmid39327050, year = {2024}, author = {Wang, Y and Li, M and Zhang, B and Feng, Y and Yu, Y and Guo, L and Du, M and Yan, W and Liu, Q and Qin, C and Deng, J and Song, C and Liu, J}, title = {Interaction between economic status and healthy lifestyle in long COVID among Chinese older population: a cross-sectional study.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e082314}, pmid = {39327050}, issn = {2044-6055}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology ; Cross-Sectional Studies ; East Asian People ; *Economic Status ; Exercise ; Health Behavior ; *Healthy Lifestyle ; Pandemics ; Smoking/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology ; }, abstract = {OBJECTIVES: To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2.

DESIGN: A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan.

SETTING: All primary health institutions in Anning, Yunnan Province, China, from April to May 2023.

PARTICIPANTS: A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study.

Long COVID was measured by participants' self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants' ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term.

RESULTS: We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction <0.001) in long COVID.

CONCLUSION: The interaction between ES and healthy lifestyle in long COVID was prominent. Comprehensive strengthened economic support for patients recovering from COVID-19, especially for those with low healthy lifestyle, should be implemented to prevent and manage long COVID symptoms.}, } @article {pmid39326914, year = {2024}, author = {Gerayeli, FV and Park, HY and Milne, S and Li, X and Yang, CX and Tuong, J and Eddy, RL and Vahedi, SM and Guinto, E and Cheung, CY and Yang, JSW and Gilchrist, C and Yehia, D and Stach, T and Dang, H and Leung, C and Shaipanich, T and Leipsic, J and Koelwyn, GJ and Leung, JM and Sin, DD}, title = {Single-cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID.}, journal = {The European respiratory journal}, volume = {64}, number = {5}, pages = {}, pmid = {39326914}, issn = {1399-3003}, mesh = {Humans ; *COVID-19/genetics/virology ; *Single-Cell Analysis ; Male ; Female ; Middle Aged ; Aged ; *SARS-CoV-2 ; *Respiratory Mucosa/metabolism/virology ; Bronchoscopy ; Neutrophils/metabolism ; Post-Acute COVID-19 Syndrome ; Transcriptome ; Case-Control Studies ; Adult ; }, abstract = {AIM: To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms.

METHOD: Adults with and without long COVID were recruited from the general community in Greater Vancouver, Canada. The cohort was divided into those with pulmonary long COVID, which was defined as persons with new or worsening respiratory symptoms following ≥12 weeks from their initial acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (n=9); and control subjects defined as SARS-CoV-2 infected persons whose acute respiratory symptoms had fully resolved or individuals who had no history of acute coronavirus disease 2019 (COVID-19) (n=9). These participants underwent bronchoscopy from which a single cell suspension was created from bronchial brush samples and then sequenced.

RESULTS: A total of 56 906 cells were recovered for the downstream analysis, with 34 840 cells belonging to the pulmonary long COVID group, which strikingly showed a unique cluster of neutrophils in the pulmonary long COVID group (p<0.05). Ingenuity Pathway Analysis revealed that the neutrophil degranulation pathway was enriched across epithelial cell clusters. Differential gene expression analysis between the pulmonary long COVID and control groups demonstrated upregulation of inflammatory chemokines and epithelial barrier dysfunction across epithelial cell clusters, as well as over-expression of mucin genes across secretory cell clusters.

CONCLUSION: A single-cell transcriptomic landscape of the small airways suggest that neutrophils may play a significant role in mediating the chronic small airway inflammation driving pulmonary symptoms of long COVID.}, } @article {pmid39326440, year = {2025}, author = {Bonnet, U and Juckel, G}, title = {News on the Role of Antidepressants in and for COVID-19 and Long COVID.}, journal = {Pharmacopsychiatry}, volume = {58}, number = {1}, pages = {41-44}, doi = {10.1055/a-2381-2117}, pmid = {39326440}, issn = {1439-0795}, } @article {pmid39326415, year = {2024}, author = {Peluso, MJ and Deeks, SG}, title = {Mechanisms of long COVID and the path toward therapeutics.}, journal = {Cell}, volume = {187}, number = {20}, pages = {5500-5529}, pmid = {39326415}, issn = {1097-4172}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/virology/complications/therapy ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Animals ; COVID-19 Drug Treatment ; }, abstract = {Long COVID, a type of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) defined by medically unexplained symptoms following infection with SARS-CoV-2, is a newly recognized infection-associated chronic condition that causes disability in some people. Substantial progress has been made in defining its epidemiology, biology, and pathophysiology. However, there is no cure for the tens of millions of people believed to be experiencing long COVID, and industry engagement in developing therapeutics has been limited. Here, we review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. Progress toward preventing and curing long COVID and other infection-associated chronic conditions will require deep and sustained investment by funders and industry.}, } @article {pmid39326207, year = {2024}, author = {Li, C and Xiao, N and Song, W and Lam, AH and Liu, F and Cui, X and Ye, Z and Chen, Y and Ren, P and Cai, J and Lee, AC and Chen, H and Ou, Z and Chan, JF and Yuen, KY and Chu, H and Zhang, AJ}, title = {Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters.}, journal = {EBioMedicine}, volume = {108}, number = {}, pages = {105363}, pmid = {39326207}, issn = {2352-3964}, mesh = {Animals ; *COVID-19/pathology/virology/metabolism ; *SARS-CoV-2/physiology ; *Cell Proliferation ; Male ; Cricetinae ; Disease Models, Animal ; Pulmonary Alveoli/pathology/virology/metabolism ; Lung/pathology/virology/metabolism ; Signal Transduction ; Pneumonia/virology/metabolism/pathology ; Receptors, Notch/metabolism/genetics ; Humans ; }, abstract = {BACKGROUND: Post-acute sequalae of COVID-19 defines a wide range of ongoing symptoms and conditions long after SARS-CoV-2 infection including respiratory diseases. The histopathological changes in the lung and underlying mechanism remain elusive.

METHODS: We investigated lung histopathological and transcriptional changes in SARS-CoV-2-infected male hamsters at 7, 14, 42, 84 and 120dpi, and compared with A (H1N1)pdm09 infection.

FINDINGS: We demonstrated viral residue, inflammatory and fibrotic changes in lung after SARS-CoV-2 but not H1N1 infection. The most prominent histopathological lesion was multifocal alveolar-bronchiolization observed in every SARS-CoV-2 infected hamster (31/31), from 42dpi to 120dpi. Proliferating (Ki67+) CK14+ basal cells accumulated in alveoli adjacent to bronchioles at 7dpi, where they proliferated and differentiated into SCGB1A+ club cell or Tubulin+ ciliated cells forming alveolar-bronchiolization foci. Molecularly, Notch pathway significantly upregulated with intensive Notch3 and Hes1 protein expression in alveolar-bronchiolization foci at 42 and 120dpi, suggesting Notch signaling involving the persistence of alveolar-bronchiolization. This is further demonstrated by spatial transcriptomic analysis. Intriguingly, significant upregulation of some cell-growth promoting pathways and genes such as Tubb4b, Stxbp4, Grb14 and Mlf1 were spatially overlapping with bronchiolization lesion.

INTERPRETATION: Incomplete resolution of SARS-CoV-2 infection in lung with viral residue, chronic inflammatory and fibrotic damage and alveolar-bronchiolization impaired respiratory function. Aberrant activation of CK14+ basal cells during tissue regeneration led to persistent alveolar-bronchiolization due to sustained Notch signaling. This study advances our understanding of respiratory PASC, sheds light on disease management and highlights the necessity for monitoring disease progression in people with respiratory PASC.

FUNDING: Funding is listed in the Acknowledgements section.}, } @article {pmid39324686, year = {2024}, author = {Quan, SF and Weaver, MD and Czeisler, MÉ and Barger, LK and Booker, LA and Howard, ME and Jackson, ML and Lane, RI and McDonald, CF and Ridgers, A and Robbins, R and Varma, P and Wiley, JF and Rajaratnam, SMW and Czeisler, CA}, title = {Sleep and long COVID: preexisting sleep issues and the risk of PASC in a large general population using 3 different model definitions.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {}, number = {}, pages = {}, doi = {10.5664/jcsm.11322}, pmid = {39324686}, issn = {1550-9397}, abstract = {STUDY OBJECTIVES: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

METHODS: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC. Three definitions of PASC were used based on post COVID-19 clinical features: COPE (≥3), NICE (≥1), and RECOVER (scoring algorithm).

RESULTS: Prevalence rates of PASC were 21.9%, 38.9%, 15.5% for COPE, NICE and RECOVER PASC definitions, respectively. PASC was associated with insomnia in all 3 models after full adjustment with odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models.

CONCLUSIONS: Insomnia, poor sleep quality and short sleep duration are cross-sectionally associated with PASC and may be potential risk factors. Further longitudinal studies should be conducted.}, } @article {pmid39324381, year = {2024}, author = {Lowe, A and Sabati, A and Bhatia, R}, title = {Use of cardiopulmonary exercise testing to identify mechanisms of exertional symptoms in children with long COVID.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1002/pmrj.13263}, pmid = {39324381}, issn = {1934-1563}, abstract = {BACKGROUND: Little is known about the mechanisms of exercise intolerance and exertional symptoms in children with long COVID. Through utilization of cardiopulmonary exercise testing (CPET), this study is the first of its kind to evaluate exertional symptoms and attempt to identify potential mechanism of long COVID-19 in children.

OBJECTIVE: To determine if CPET will uncover potential reasons for persistent symptoms of long COVID when there is no indication of cardiopulmonary or upper airway disease.

METHODS: We performed a retrospective chart review study involving children 6-17 years of age with symptoms of long COVID at Phoenix Children''s Hospital from January 1, 2021, to June 1, 2022. Symptoms included but were not limited to exercise intolerance, fatigue, shortness of breath, dyspnea on exertion, and chest pain. We recorded any measurable abnormalities present on CPET after comparing it to established normal reference ranges. Range, median, and SD of data points were calculated and p values were determined using the Mann-Whitney U and Fisher's exact test.

RESULTS: Twenty-three children with exertional symptoms consistent with long COVID were identified. The most frequent symptoms reported during exercise include dyspnea on exertion (35%), followed by chest pain (30%) and dizziness (13%). Nearly half of the children (47%) demonstrated decreased exercise capacity with 30% displaying limitations due to deconditioning, 22% limited by body habitus, and 13% due to bronchospasm. Other contributing factors include ventilation to perfusion mismatch and volitional hyperventilation.

CONCLUSION: Decreased aerobic activity due to multiple factors was found in 47% of children with a history of COVID-19. This study illustrates the importance of ongoing research into this phenomenon to elucidate its mechanism and assist physicians in making decisions regarding referral to specialists for further testing.}, } @article {pmid39323692, year = {2024}, author = {Hameed, M and Abbasi, MA and Noor, F and Fatima, A and Ibrahim, M and Bano, S and Hamza, A and Rasool Malik, AA and Saeed, MA and Iqbal, S}, title = {Exploring Neurocognitive and Emotional Outcomes of Long COVID: A Study Among Pakistani Patients.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67815}, pmid = {39323692}, issn = {2168-8184}, abstract = {Background and objective Coronavirus disease 2019 (COVID-19), primarily a respiratory illness, also significantly impacts neurocognitive and emotional health, particularly in its long-term manifestation known as long COVID. This study aimed to investigate the neurocognitive and emotional outcomes of long-term COVID-19 in Pakistani patients, to address the persisting symptoms and their effects on mental health and cognitive function. Methods A cross-sectional study involving 100 adult participants who had been COVID-19-free was conducted in Islamabad between March 2022 and March 2023. Participants were assessed using the Mini-Mental State Examination (MMSE), attention-deficit/hyperactivity disorder (ADHD) Self-Report Questionnaire, Satisfaction with Life Scale (SWLS), and Punishing Allah Reappraisal Scale. Data were analyzed using SPSS Statistics v26 (IBM Corp., Armonk, NY), employing chi-square tests, t-tests, and ANOVA. Results The study revealed significant correlations between COVID-19 symptoms and psychological variables. COVID-19 symptoms showed a negative correlation with MMSE scores (r = -0.04, p<0.01) and positive correlations with ADHD (r = 0.13, p<0.05), depression (r = 0.14, p<0.05), and anxiety (r = 0.25, p<0.05). Females reported higher levels of depression [mean: 1.21, standard deviation (SD): 0.83] and anxiety (mean: 1.33, SD: 0.86) compared to males. Conclusions Our findings highlight the extensive impact of long-term COVID-19 on neurocognitive and emotional health, with significant gender differences observed in emotional outcomes. These results emphasize the need for integrated mental health services in post-COVID-19 care plans, as well as gender-sensitive interventions.}, } @article {pmid39322885, year = {2024}, author = {Diener, HC}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {16}, pages = {27-28}, doi = {10.1007/s15006-024-4305-5}, pmid = {39322885}, issn = {1613-3560}, mesh = {Humans ; *COVID-19/epidemiology ; *Mental Disorders/epidemiology/psychology/therapy ; SARS-CoV-2 ; Germany ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid39322271, year = {2024}, author = {}, title = {Long COVID in children and adolescents. What is it?.}, journal = {Archives of disease in childhood}, volume = {109}, number = {10}, pages = {867}, doi = {10.1136/archdischild-2024-327935}, pmid = {39322271}, issn = {1468-2044}, mesh = {Humans ; Child ; Adolescent ; *COVID-19/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; }, } @article {pmid39321500, year = {2024}, author = {Bergquist, T and Loomba, J and Pfaff, E and Xia, F and Zhao, Z and Zhu, Y and Mitchell, E and Bhattacharya, B and Shetty, G and Munia, T and Delong, G and Tariq, A and Butzin-Dozier, Z and Ji, Y and Li, H and Coyle, J and Shi, S and Philips, RV and Mertens, A and Pirracchio, R and van der Laan, M and Colford, JM and Hubbard, A and Gao, J and Chen, G and Velingker, N and Li, Z and Wu, Y and Stein, A and Huang, J and Dai, Z and Long, Q and Naik, M and Holmes, J and Mowery, D and Wong, E and Parekh, R and Getzen, E and Hightower, J and Blase, J and , and , }, title = {Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.}, journal = {EBioMedicine}, volume = {108}, number = {}, pages = {105333}, pmid = {39321500}, issn = {2352-3964}, mesh = {Humans ; *COVID-19/epidemiology ; *Machine Learning ; *SARS-CoV-2/isolation & purification ; United States/epidemiology ; Algorithms ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Crowdsourcing ; }, abstract = {BACKGROUND: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID.

METHODS: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.).

FINDINGS: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events.

INTERPRETATION: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions.

FUNDING: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.}, } @article {pmid39320278, year = {2024}, author = {Rodriguez, RM and Reyes, K and Kumar, VA and Chinnock, B and Eucker, SA and Rising, KL and Rafique, Z and Gottlieb, M and Nichol, G and Morse, D and Molina, M and Arreguin, MI and Shughart, L and Conn, C and Eckstrand, S and Mesbah, H and Chakraborty, L and Welch, RD}, title = {Long COVID Illness: Disparities in Understanding and Receipt of Care in Emergency Department Populations.}, journal = {Annals of emergency medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.annemergmed.2024.07.009}, pmid = {39320278}, issn = {1097-6760}, abstract = {STUDY OBJECTIVE: Most long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms.

METHODS: This study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID illness were measured. Prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms were also assessed.

RESULTS: Of 1,618 eligible patients, 1455 (89.9%) agreed to participate, including 33.4% African Americans and 30.9% Latino/a. Of the patients, 17.1% lacked primary care. In total, 33.2% had persistent COVID-19 symptoms lasting >1 month, and 20.3% had symptoms >3 months. Moreover, 49.8% with long COVID symptoms missed work/school because of symptoms; 30.3% of all participants and 33.5% of participants who had long COVID symptoms had prior awareness and self-declared understanding of long COVID. Characteristics associated with poor understanding of long COVID were African American race (adjusted odds ratio [aOR] 3.68, 95% confidence interval [CI] 2.66 to 5.09) and Latino/a ethnicity (aOR 3.16, 95% CI 2.15 to 4.64). Participants lacking primary care were less likely to have received long COVID care (24.6% versus 51.2%; difference 26.6%; 95% CI 13.7% to 36.9%).

CONCLUSIONS: Despite high prevalence and impact on school/work attendance of long COVID symptoms, most of this ED population had limited awareness and self-declared understanding of long COVID, and many had not received care. EDs should consider the development of protocols for diagnosis, education, and treatment of long COVID illness.}, } @article {pmid39319349, year = {2024}, author = {Devkota, S and Garg, M and Debi, U and Dhooria, S and Dua, A and Prabhakar, N and Soni, S and Maralakunte, M and Gulati, A and Singh, T and Sandhu, MS}, title = {Evaluating Lung Changes in Long COVID: Ultra-Low-Dose vs. Standard-Dose CT Chest.}, journal = {British journal of biomedical science}, volume = {81}, number = {}, pages = {13385}, pmid = {39319349}, issn = {2474-0896}, mesh = {Humans ; *COVID-19/diagnostic imaging ; Male ; Female ; Middle Aged ; *Tomography, X-Ray Computed/methods ; *Lung/diagnostic imaging/pathology ; *Radiation Dosage ; Adult ; Prospective Studies ; Aged ; SARS-CoV-2 ; Signal-To-Noise Ratio ; }, abstract = {BACKGROUND: Frequent chest CTs within a short period during follow-up of long COVID patients may increase the risk of radiation-related health effects in the exposed individuals. We aimed to assess the image quality and diagnostic accuracy of ultra-low-dose CT (ULDCT) chest compared to standard-dose CT (SDCT) in detecting lung abnormalities associated with long COVID.

METHODS: In this prospective study, 100 long COVID patients with respiratory dysfunction underwent SDCT and ULDCT chest that were compared in terms of objective (signal-to-noise ratio, SNR) and subjective image quality (image graininess, sharpness, artifacts, and diagnostic accuracy along with the European guidelines on image quality criteria for CT chest), detection of imaging patterns of long COVID, CT severity score, and effective radiation dose. Additionally, the diagnostic performance of ULDCT was compared among obese (BMI≥30 kg/m[2]) and non-obese (BMI<30 kg/m[2]) subjects.

RESULTS: The mean age of study participants was 53 ± 12.9 years, and 68% were male. The mean SNR was 31.4 ± 5.5 and 11.3 ± 4.6 for SDCT and ULDCT respectively (p< 0.0001). Common findings seen on SDCT included ground-glass opacities (GGOs, 77%), septal thickening/reticulations (67%), atelectatic/parenchymal bands (63%) and nodules (26%). ULDCT provided sharp images, with no/minimal graininess, and high diagnostic confidence in 81%, 82% and 80% of the cases respectively. The sensitivity of ULDCT for various patterns of long COVID was 72.7% (GGOs), 71.6% (interlobular septal thickening/reticulations), 100% (consolidation), 81% (atelectatic/parenchymal bands) and 76.9% (nodules). ULDCT scans in non-obese subjects exhibited a significantly higher sensitivity (88% vs. 60.3%, p < 0.0001) and diagnostic accuracy (97.7% vs. 84.9%, p < 0.0001) compared to obese subjects. ULDCT showed very strong correlation with SDCT in terms of CT severity score (r = 0.996, p < 0.0001). The mean effective radiation dose with ULDCT was 0.25 ± 0.02 mSv with net radiation dose reduction of 94.8% ± 1.7% (p < 0.0001) when compared to SDCT (5.5 ± 1.96 mSv).

CONCLUSION: ULDCT scans achieved comparable diagnostic accuracy to SDCT for detecting long COVID lung abnormalities in non-obese patients, while significantly reducing radiation exposure.}, } @article {pmid39317338, year = {2024}, author = {Liu, T and Kang, H}, title = {The risk factors for long term cardiovascular symptoms in patients after coronavirus disease 2019 infection.}, journal = {Annals of medicine}, volume = {56}, number = {1}, pages = {2407065}, pmid = {39317338}, issn = {1365-2060}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Retrospective Studies ; *Cardiovascular Diseases/epidemiology/etiology ; Risk Factors ; *SARS-CoV-2 ; Aged ; C-Reactive Protein/analysis/metabolism ; Adult ; Anxiety/epidemiology ; Fibrin Fibrinogen Degradation Products/analysis/metabolism ; Depression/epidemiology ; China/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Presently, numerous studies have demonstrated that long-term cardiovascular changes after Coronavirus Disease 2019(COVID-19) infection should be considered. The study was aimed to explore the risk factors for post COVID-19 long-term cardiovascular symptoms.

METHODS: This retrospective observational cross-sectional study involved 204 COVID-19 patients who were admitted to Yantaishan Hospital from January 1, 2023 to January 31, 2023. Demographic and laboratory data were collected and compared between patients who experienced post COVID-19 long-term cardiovascular symptoms and those who did not. Logistic regression analysis was used to identify the risk factors associated with the occurrence of post COVID-19 long-term cardiovascular symptoms.

RESULTS: Fifty-two participants presented Post COVID-19 cardiovascular symptoms, while the remaining 152 individuals did not show any such symptoms including chest pain, chest tightness, shortness of breath, palpitations, dyspnea, exercise intolerance, and postural tachycardia syndrome. In comparison to the group without post COVID-19 long-term cardiovascular symptoms, the group with post COVID-19 long-term cardiovascular symptoms exhibited a significantly higher prevalence of anxiety and depression (25.0% vs. 4.6%, p = 0.000), as well as significantly elevated C-reactive protein (42.3 mg/L vs. 20.3 mg/L, p = 0.014) and D-dimer (0.3 mg/L vs. 0.22 mg/L, p = 0.024). Anxiety and depression (odds ratio [OR] = 6.403, 95% confidence interval [CI]:2.180-18.809, p = 0.001), C-reactive protein (OR = 1.009, 95%CI:1.003-1.015, p = 0.006), D-dimer (OR = 1.455, 95%CI:1.004-2.109, p = 0.048), and LDL-C (OR = 1.780, 95%CI:1.043-3.040, p = 0.035) were identified as independent risk factors for post COVID-19 long-term cardiovascular symptoms.

CONCLUSION: Anxiety and depression, C-reactive protein, D-dimer, and LDL-C levels are associated with the development of post COVID-19 long-term cardiovascular symptoms.}, } @article {pmid39317274, year = {2024}, author = {Nelson, BK and Farah, LN and Grier, A and Su, W and Chen, J and Sossi, V and Sekhon, MS and Stoessl, AJ and Wellington, C and Honer, WG and Lang, D and Silverberg, ND and Panenka, WJ}, title = {Differences in brain structure and cognitive performance between patients with long-COVID and those with normal recovery.}, journal = {NeuroImage}, volume = {300}, number = {}, pages = {120859}, doi = {10.1016/j.neuroimage.2024.120859}, pmid = {39317274}, issn = {1095-9572}, mesh = {Humans ; *COVID-19/pathology/diagnostic imaging ; Male ; Female ; *Diffusion Tensor Imaging/methods ; Adult ; Middle Aged ; *Brain/diagnostic imaging/pathology ; *Cognition/physiology ; White Matter/diagnostic imaging/pathology ; SARS-CoV-2 ; Neuropsychological Tests ; Aged ; Post-Acute COVID-19 Syndrome ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: The pathophysiology of protracted symptoms after COVID-19 is unclear. This study aimed to determine if long-COVID is associated with differences in baseline characteristics, markers of white matter diffusivity in the brain, and lower scores on objective cognitive testing.

METHODS: Individuals who experienced COVID-19 symptoms for more than 60 days post-infection (long-COVID) (n = 56) were compared to individuals who recovered from COVID-19 within 60 days of infection (normal recovery) (n = 35). Information regarding physical and mental health, and COVID-19 illness was collected. The National Institute of Health Toolbox Cognition Battery was administered. Participants underwent magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). Tract-based spatial statistics were used to perform a whole-brain voxel-wise analysis on standard DTI metrics (fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity), controlling for age and sex. NIH Toolbox Age-Adjusted Fluid Cognition Scores were used to compare long-COVID and normal recovery groups, covarying for Age-Adjusted Crystallized Cognition Scores and years of education. False discovery rate correction was applied for multiple comparisons.

RESULTS: There were no significant differences in age, sex, or history of neurovascular risk factors between the groups. The long-COVID group had significantly (p < 0.05) lower mean diffusivity than the normal recovery group across multiple white matter regions, including the internal capsule, anterior and superior corona radiata, corpus callosum, superior fronto-occiptal fasciculus, and posterior thalamic radiation. However, the effect sizes of these differences were small (all β<|0.3|) and no significant differences were found for the other DTI metrics. Fluid cognition composite scores did not differ significantly between the long-COVID and normal recovery groups (p > 0.05).

CONCLUSIONS: Differences in diffusivity between long-COVID and normal recovery groups were found on only one DTI metric. This could represent subtle areas of pathology such as gliosis or edema, but the small effect sizes and non-specific nature of the diffusion indices make pathological inference difficult. Although long-COVID patients reported many neuropsychiatric symptoms, significant differences in objective cognitive performance were not found.}, } @article {pmid39317224, year = {2024}, author = {Granana, N and Tarulla, A and Calandri, I and Carli, A and Rivas, B and Festa, JM and Vacirca, S and Lis, M and Worff, I and Allegri, R}, title = {Impact on the nervous system of long COVID-19 infection in children.}, journal = {Arquivos de neuro-psiquiatria}, volume = {82}, number = {9}, pages = {1-7}, doi = {10.1055/s-0044-1789224}, pmid = {39317224}, issn = {1678-4227}, mesh = {Humans ; *COVID-19/complications ; Child ; Female ; Male ; Adolescent ; Child, Preschool ; SARS-CoV-2 ; Nervous System Diseases/virology ; Risk Factors ; Time Factors ; Pandemics ; Infant ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact, raising concerns about its long-term effects, particularly neurological complications. While studies have highlighted such complications in adults, there is a paucity of research focusing on children.

OBJECTIVE:  To examine the medium- to long-term neurological and cognitive symptoms in 18 year old children and below with positive versus negative COVID-19 antigens and to identify the probable risk factors to promote specific health actions.

METHODS:  An observational study was carried out to determine neurological symptoms in the medium and long terms after COVID 19. A random sample of 124 children, both symptomatic or asymptomatic, tested positive or negative for COVID-19 through swab tests.

RESULTS:  Neurological symptoms were assessed between 6 to 12 months and 2 years after the infection. Acute symptoms, including headache, anosmia, ageusia, and myalgia, were observed in more than 20% of the children, but they generally resolved within 6 to 12 months. Persistent functional difficulties, such as in studying, paying attention, and socializing, were reported in 3% of the cases. Behavioral symptoms at baseline were noted in 7.8% of children, but they were remitted in most cases, except for those with prior involvement.

CONCLUSION:  These findings underscore the need for continued monitoring of children following COVID-19 infection and the importance of tailored health interventions.}, } @article {pmid39316344, year = {2024}, author = {Goodwill, JR and Ajibewa, TA}, title = {A Mixed Methods Analysis of Long COVID Symptoms in Black Americans: Examining Physical and Mental Health Outcomes.}, journal = {Journal of racial and ethnic health disparities}, volume = {}, number = {}, pages = {}, pmid = {39316344}, issn = {2196-8837}, abstract = {BACKGROUND: While several reports confirm that long COVID is associated with poorer health, few studies explore how long COVID directly impacts the lives of Black Americans who experienced higher mortality rates early in the pandemic. Even fewer studies utilize both quantitative and qualitative methods to identify pertinent long COVID symptoms. The current study, therefore, sought to identify points of overlap and divergence when comparing qualitative vs. quantitative descriptions of long COVID experiences among Black adults in the United States.

METHODS: We analyzed cross-sectional surveys collected from the AmeriSpeak panel through the National Opinion Research Center (NORC) at the University of Chicago. This panel includes a probability-based sample of adults across the United States. Respondents completed online surveys between April and June 2022. We compared outcomes among participants who reported experiencing post-acute sequelae of COVID-19 (i.e., long COVID) to those who reported experiencing SARS-CoV-2 without long COVID.

RESULTS: Nearly all qualitative responses focused on matters of physical health like prolonged coughing, cardiovascular concerns, troubled breathing, fatigue, headaches, memory loss, and bodily pains. Quantitative results, however, showed that Black adults living with long COVID reported significantly more anxiety, depressive symptoms, and hopelessness. Persons with long COVID were also significantly more likely to report experiencing psychosis, suicidal ideation, suicide plans, and suicide attempts within the last year.

CONCLUSIONS: Black adults with long COVID experienced worse outcomes across all mental health measures. Despite the COVID-19 Public Health Emergency expiration in May 2023, urgent efforts are still required to not only treat both the physical and mental health needs of persons living with long COVID, but to effectively prevent the spread and transmission of COVID-19.}, } @article {pmid39315181, year = {2024}, author = {Zhang, X and Wen, R and Chen, H and Liu, J and Wu, Y and Xu, M and Wang, R and Zeng, X}, title = {COVID-19 and diabetes research: Where are we now and what does the future hold? A bibliometric visualization analysis.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37615}, pmid = {39315181}, issn = {2405-8440}, abstract = {BACKGROUND & OBJECTIVE: The extensive spread of Coronavirus disease 2019 (COVID-19) worldwide has caused a dramatic negative impact on many individuals' health. This study aims to systematically and comprehensively analyze the current status and possible future directions of diabetes mellitus (DM) and COVID-19 research.

METHODS: We obtained publications about COVID-19 and DM from the Web of Science Core Collection (WoSCC) using the search terms "COVID-19″ and similar terms combined with "DM" and similar terms, with a date range of January 2020 to May 2024. And we used CiteSpace V 6.3.R2 to perform the bibliometric visualization analysis.

RESULTS: The search enrolled 6266 publications. The USA is a country with the most publications; Harvard University was the most productive institution in this field. The highest-ranked journal was the PLOS ONE, and the most cited journal was Lancet. The 20 most cited journals have all been cited 28754 times, accounting for 28 % of the total cites; the range of those journals was 790-3197. Publications on COVID-19 and DM research exhibited a distinct trajectory, shifting from an initial emphasis on understanding the impact of diabetes on COVID-19 infection and its associated pathophysiological mechanisms to a focus on analyzing the differential responses of diverse patient populations. Subsequently, research has progressed to examine the effects of medications and vaccines, as well as the long-term consequences of COVID-19 in diabetic individuals. Throughout this research endeavor, the exploration of diverse therapeutic interventions, their efficacy, and ultimate outcomes have consistently remained a paramount focus. And " metabolic syndrome," " long COVID," and " gestational diabetes" are still likely to be the hotspots and frontiers of research in the future.

CONCLUSIONS: This bibliometric analysis related to DM in COVID-19 illuminates the current research situation and developmental trends, supporting researchers in the exploration of prospective directions for research.}, } @article {pmid39314791, year = {2024}, author = {Bowie, C and Friston, K}, title = {A follow up report validating long term predictions of the COVID-19 epidemic in the UK using a dynamic causal model.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1398297}, pmid = {39314791}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology/transmission/mortality ; United Kingdom/epidemiology ; *SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Follow-Up Studies ; Forecasting ; }, abstract = {BACKGROUND: This paper asks whether Dynamic Causal modelling (DCM) can predict the long-term clinical impact of the COVID-19 epidemic. DCMs are designed to continually assimilate data and modify model parameters, such as transmissibility of the virus, changes in social distancing and vaccine coverage-to accommodate changes in population dynamics and virus behavior. But as a novel way to model epidemics do they produce valid predictions? We presented DCM predictions 12 months ago, which suggested an increase in viral transmission was accompanied by a reduction in pathogenicity. These changes provided plausible reasons why the model underestimated deaths, hospital admissions and acute-post COVID-19 syndrome by 20%. A further 12-month validation exercise could help to assess how useful such predictions are.

METHODS: we compared DCM predictions-made in October 2022-with actual outcomes over the 12-months to October 2023. The model was then used to identify changes in COVID-19 transmissibility and the sociobehavioral responses that may explain discrepancies between predictions and outcomes over this period. The model was then used to predict future trends in infections, long-COVID, hospital admissions and deaths over 12-months to October 2024, as a prelude to future tests of predictive validity.

FINDINGS: Unlike the previous predictions-which were an underestimate-the predictions made in October 2022 overestimated incidence, death and admission rates. This overestimation appears to have been caused by reduced infectivity of new variants, less movement of people and a higher persistence of immunity following natural infection and vaccination.

INTERPRETATION: despite an expressive (generative) model, with time-dependent epidemiological and sociobehavioral parameters, the model overestimated morbidity and mortality. Effectively, the model failed to accommodate the "law of declining virulence" over a timescale of years. This speaks to a fundamental issue in long-term forecasting: how to model decreases in virulence over a timescale of years? A potential answer may be available in a year when the predictions for 2024-under a model with slowly accumulating T-cell like immunity-can be assessed against actual outcomes.}, } @article {pmid39314212, year = {2024}, author = {Oropeza-Valdez, JJ and Padron-Manrique, C and Vázquez-Jiménez, A and Soberon, X and Resendis-Antonio, O}, title = {Exploring metabolic anomalies in COVID-19 and post-COVID-19: a machine learning approach with explainable artificial intelligence.}, journal = {Frontiers in molecular biosciences}, volume = {11}, number = {}, pages = {1429281}, pmid = {39314212}, issn = {2296-889X}, abstract = {The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant challenges worldwide, including diverse clinical outcomes and prolonged post-recovery symptoms known as Long COVID or Post-COVID-19 syndrome. Emerging evidence suggests a crucial role of metabolic reprogramming in the infection's long-term consequences. This study employs a novel approach utilizing machine learning (ML) and explainable artificial intelligence (XAI) to analyze metabolic alterations in COVID-19 and Post-COVID-19 patients. Samples were taken from a cohort of 142 COVID-19, 48 Post-COVID-19, and 38 control patients, comprising 111 identified metabolites. Traditional analysis methods, like PCA and PLS-DA, were compared with ML techniques, particularly eXtreme Gradient Boosting (XGBoost) enhanced by SHAP (SHapley Additive exPlanations) values for explainability. XGBoost, combined with SHAP, outperformed traditional methods, demonstrating superior predictive performance and providing new insights into the metabolic basis of the disease's progression and aftermath. The analysis revealed metabolomic subgroups within the COVID-19 and Post-COVID-19 conditions, suggesting heterogeneous metabolic responses to the infection and its long-term impacts. Key metabolic signatures in Post-COVID-19 include taurine, glutamine, alpha-Ketoglutaric acid, and LysoPC a C16:0. This study highlights the potential of integrating ML and XAI for a fine-grained description in metabolomics research, offering a more detailed understanding of metabolic anomalies in COVID-19 and Post-COVID-19 conditions.}, } @article {pmid39313202, year = {2024}, author = {Bonnet, U and Juckel, G}, title = {[The Impact of Antidepressants on COVID-19 and Post-Acute COVID-19 Syndrome: A Scoping-Review Update].}, journal = {Fortschritte der Neurologie-Psychiatrie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2374-2218}, pmid = {39313202}, issn = {1439-3522}, abstract = {UNLABELLED: Introduction Preclinically, fluvoxamine and other antidepressants (AD) exerted antiviral and anti-inflammatory properties also against SARS-COV-2. Therfore, It makes sense to test the clinical effect of AD against COVID-19 and Long COVID.

METHODS: On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses.

RESULTS: COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue.

CONCLUSION: Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.}, } @article {pmid39311897, year = {2024}, author = {Pinto Pereira, SM and Newlands, F and Anders, J and Banerjee, A and Beale, S and Blandford, A and Brown, K and Bu, F and Fong, WLE and Gilpin, G and Hardelid, P and Kovar, J and Lim, J and Park, C and Raveendran, V and Shah, AD and Shao, X and Wong, A and Stephenson, T and Shafran, R}, title = {Long COVID: what do we know now and what are the challenges ahead?.}, journal = {Journal of the Royal Society of Medicine}, volume = {117}, number = {7}, pages = {224-228}, pmid = {39311897}, issn = {1758-1095}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; }, } @article {pmid39311385, year = {2024}, author = {Timofeeva, AM and Nikitin, AO and Nevinsky, GA}, title = {Circulating miRNAs in the Plasma of Post-COVID-19 Patients with Typical Recovery and Those with Long-COVID Symptoms: Regulation of Immune Response-Associated Pathways.}, journal = {Non-coding RNA}, volume = {10}, number = {5}, pages = {}, pmid = {39311385}, issn = {2311-553X}, support = {22-15-00103//Russian Science Foundation/ ; 0245-2021-0009 (121031300041-4)//Russian State-funded budget project of ICBFM SB RAS/ ; }, abstract = {Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways.}, } @article {pmid39311110, year = {2024}, author = {Vontetsianos, A and Chynkiamis, N and Anagnostopoulou, C and Lekka, C and Zaneli, S and Anagnostopoulos, N and Rovina, N and Kampolis, CF and Papaioannou, AI and Kaltsakas, G and Vogiatzis, I and Stratakos, G and Bakakos, P and Koulouris, N}, title = {Small Airways Dysfunction and Lung Hyperinflation in Long COVID-19 Patients as Potential Mechanisms of Persistent Dyspnoea.}, journal = {Advances in respiratory medicine}, volume = {92}, number = {5}, pages = {329-337}, pmid = {39311110}, issn = {2543-6031}, mesh = {Humans ; *COVID-19/physiopathology/complications ; *Dyspnea/physiopathology/etiology ; Middle Aged ; Male ; Female ; *Respiratory Function Tests ; Lung/physiopathology/diagnostic imaging ; SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BACKGROUND: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19.

AIM: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness.

METHODS: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W).

RESULTS: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010).

CONCLUSIONS: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.}, } @article {pmid39311094, year = {2024}, author = {Hori, M and Hayama-Terada, M and Kitamura, A and Hosozawa, M and Muto, Y and Iba, A and Takayama, Y and Kimura, T and Iso, H}, title = {Risk factors for post-coronavirus disease condition in the Alpha-, Delta-, and Omicron-dominant waves among adults in Japan: A population-based matched case-control study.}, journal = {Journal of medical virology}, volume = {96}, number = {9}, pages = {e29928}, doi = {10.1002/jmv.29928}, pmid = {39311094}, issn = {1096-9071}, support = {JPMH21HA2011//This study was supported by the Ministry of Health, Labour and Welfare Research Program on Emerging and Re-emerging Infectious Diseases/ ; }, mesh = {Humans ; Middle Aged ; Adult ; Female ; Male ; *COVID-19/epidemiology ; Case-Control Studies ; Japan/epidemiology ; Risk Factors ; Aged ; *SARS-CoV-2/immunology ; Young Adult ; Adolescent ; COVID-19 Vaccines/administration & dosage ; Vaccination/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Registries ; }, abstract = {Vaccination is associated with a reduced risk of post-coronavirus disease (COVID-19) condition (PCC). Here, risk factors including vaccination for PCC in the Omicron-dominant waves among Japanese adults were investigated. This was a registry-based matched case-control study of individuals aged 18-79 years diagnosed with COVID-19 registered in a National database between March 2021 and April 2022 and matched noninfected individuals living in Yao City, Japan. A self-administered questionnaire was used to assess persistent symptoms and their risk factors. The COVID-19 vaccination status was obtained from the Vaccination Registry. PCC risk factors were analyzed using logistic regression after adjusting for potential confounding factors. Overall, 4185 infected (cases) and 3382 noninfected (controls) individuals were included in the analysis. The mean ages and proportions of women were 44.7 years and 60.2% and 45.5 years and 60.7% for cases and controls, respectively. A total of 3805 (90.9%) participants had asymptomatic or mild acute symptoms at the median (range) follow-up of 271 (185-605) days. The prevalence of PCC was 15.0% for cases while that of persistent symptoms was 4.4% for controls; among the cases, it was 27.0% in the Alpha- and Delta-dominant waves and 12.8% in the Omicron-dominant wave. Female sex, comorbidities, and hospitalization were positively associated with PCC. One or more vaccine doses of vaccination were inversely associated with PCC; the inverse association was stronger in the Alpha- and Delta-dominant waves (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.12-0.73) than in the Omicron-dominant wave (aOR: 0.79, 95% CI: 0.59-1.07).}, } @article {pmid39310121, year = {2024}, author = {Zhai, X and Wu, W and Zeng, S and Miao, Y}, title = {Advance in the mechanism and clinical research of myalgia in long COVID.}, journal = {American journal of clinical and experimental immunology}, volume = {13}, number = {4}, pages = {142-164}, pmid = {39310121}, issn = {2164-7712}, abstract = {As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, mortality rates of coronavirus disease 2019 (COVID-19) have significantly decreased. However, a variable proportion of patients exhibit persistent prolonged symptoms of COVID-19 infection (long COVID). This virus primarily attacks respiratory system, but numerous individuals complain persistent skeletal muscle pain or worsening pre-existing muscle pain post COVID-19, which severely affects the quality of life and recovery. Currently, there is limited research on the skeletal muscle pain in long COVID. In this brief review, we review potential pathological mechanisms of skeletal muscle pain in long COVID, and summarize the various auxiliary examinations and treatments for skeletal muscle pain in long COVID. We consider abnormal activation of inflammatory response, myopathy, and neurological damages as pivotal pathological mechanisms of skeletal muscle pain in long COVID. A comprehensive examination is significantly important in order to work out effective treatment plans and relieve skeletal muscle pain. So far, rehabilitation interventions for myalgia in long COVID contain but are not limited to drug, nutraceutical therapy, gut microbiome-targeted therapy, interventional therapy and strength training. Our study provides a potential mechanism reference for clinical researches, highlighting the importance of comprehensive approach and management of skeletal muscle pain in long COVID. The relief of skeletal muscle pain will accelerate rehabilitation process, improve activities of daily living and enhance the quality of life, promoting individuals return to society with profound significance.}, } @article {pmid39308483, year = {2024}, author = {Gautier, SCZ and Coneti, V and Horton, DB and Greenberg, P and Andrews, T and Barrett, ES and Carson, JL and Blaser, MJ and Panettieri, RA and Rawal, S}, title = {Long-term recovery of taste and smell following acute COVID-19 infection in a New Jersey cohort.}, journal = {Science talks}, volume = {11}, number = {}, pages = {}, pmid = {39308483}, issn = {2772-5693}, support = {R01 AI158911/AI/NIAID NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; }, abstract = {Loss of taste and smell is one of the most troubling symptoms of long COVID and may be permanent for some. Correlation between subjectively and objectively assessed olfactory and gustatory impairment is low, leading to uncertainty about how many people are affected, how many recover, and to what extent. We prospectively investigated the effects of COVID-19 on long-term chemosensory function in a university and hospital-based cohort in NJ. We followed 856 participants from March 2020 through April 2022, of which 58 were diagnosed with COVID-19 and completed the NHANES 2013-2014 taste and smell protocol, including a chemosensory questionnaire, whole-mouth taste tests, and an 8-item odor identification test at and/or before acute COVID-19 infection. Of these, 29 repeated taste and smell assessments at 6 months (183.0 ± 54.6) follow-up. Total overall smell score significantly improved from baseline to 6-month follow up (6.9 ± 1.4 vs 7.6 ± 0.8; p = .01). Taste intensity also improved across 6 months, but not significantly. Our study is the first to show psychophysically-assessed and self-reported long-term recovery of olfactory and gustatory function in the same population after acute COVID-19.}, } @article {pmid39305184, year = {2025}, author = {Prem, B and Liu, DT and Boehme, K and Maurer, MT and Renner, B and Mueller, CA}, title = {Factors Associated With Persisting Olfactory Dysfunction After COVID-19.}, journal = {Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery}, volume = {50}, number = {1}, pages = {53-61}, pmid = {39305184}, issn = {1749-4486}, support = {22194//Medical Scientific Fund of the Mayor of the City of Vienna/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Female ; Male ; *Olfaction Disorders/etiology/virology/diagnosis/physiopathology ; Adult ; Middle Aged ; *SARS-CoV-2 ; Surveys and Questionnaires ; Longitudinal Studies ; Aged ; }, abstract = {BACKGROUND: Fortunately, the majority of COVID-19 patients recover from olfactory dysfunction (OD) within the first couple of weeks. However, from approximately 5% up to 20% continue to suffer from OD even more than 1 year after the onset. Nonetheless, factors associated with long-lasting OD are hardly known. The aim of this study was to identify favourable and disadvantageous markers of persisting OD in COVID-19 patients.

METHODOLOGY: Sixty-six patients (46 female; mean age: 39.9 years) that suffer from OD longer than 6 months due to laboratory-confirmed SARS-CoV-2 infection have participated in this longitudinal study. Participants completed comprehensive psychophysical chemosensory tests (i.e., Sniffin' Sticks = TDI) and questionnaires twice at our department-on average 219 ± 80 (T-1) and 489 ± 89 (T-2) days after the onset of symptoms, respectively. Olfactory recovery rates were associated with demographic factors and questionnaires using linear regression analysis.

RESULTS: Patients below 40 years of age improved better (TDI: 4.1 ± 4.3 vs. 0.7 ± 5.8; p = 0.008) and achieved statistically significant higher scores (TDI: 31.5 ± 4.0 vs. 27.3 ± 6.7; p = 0.033) regarding psychophysical chemosensory tests. Furthermore, linear regression analysis revealed that parosmia was associated with worse orthonasal smell function (T-1: β = -0.346, p = 0.004; T-2: β = -0.384, p = 0.001), especially concerning identification subtest (T-1: β = -0.395, p = 0.001; T-2: β = -0.398, p < 0.001). Moreover, increasing parosmia between T-1and T-2 led to worse orthonasal olfactory function (β = -0.294, p = 0.016).

CONCLUSIONS: Older age and parosmia seem to be unfavourable factors of persisting OD in COVID-19 patients.}, } @article {pmid39301475, year = {2024}, author = {Ganesh, R and Munipalli, B}, title = {Long COVID and hypermobility spectrum disorders have shared pathophysiology.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1455498}, pmid = {39301475}, issn = {1664-2295}, abstract = {Hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS) are the most common joint hypermobility conditions encountered by physicians, with hypermobile and classical EDS accounting for >90% of all cases. Hypermobility has been detected in up to 30-57% of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, postural orthostatic tachycardia syndrome (POTS), and long COVID (LC) compared to the general population. Extrapulmonary symptoms, including musculoskeletal pain, dysautonomia disorders, cognitive disorders, and fatigue, are seen in both LC and HSD. Additionally, ME/CFS has overlapping symptoms with those seen in HSD. Mast cell activation and degranulation occurring in both LC and ME/CFS may result in hyperinflammation and damage to connective tissue in these patients, thereby inducing hypermobility. Persistent inflammation may result in the development or worsening of HSD. Hence, screening for hypermobility and other related conditions including fibromyalgia, POTS, ME/CFS, chronic pain conditions, joint pain, and myalgia is essential for individuals experiencing LC. Pharmacological treatments should be symptom-focused and geared to a patient's presentation. Paced exercise, massage, yoga, and meditation may also provide benefits.}, } @article {pmid39300811, year = {2024}, author = {Zhao, X and Chen, L and Huo, L and Wang, M and Gao, Z and Jiang, H and Wei, L}, title = {Prevalence and risk factors of long COVID among maintenance hemodialysis patients post SARS-CoV-2 infection: A one-year follow-up study in China.}, journal = {Journal of medical virology}, volume = {96}, number = {9}, pages = {e29932}, doi = {10.1002/jmv.29932}, pmid = {39300811}, issn = {1096-9071}, support = {82301749//National Natural Science Foundation of China/ ; 82170755//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; *Renal Dialysis/adverse effects ; Male ; China/epidemiology ; Risk Factors ; Middle Aged ; Follow-Up Studies ; Prevalence ; Aged ; *SARS-CoV-2 ; Adult ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Comorbidity ; Surveys and Questionnaires ; Fatigue/epidemiology ; }, abstract = {Patients undergoing maintenance hemodialysis (MHD) are a high-risk group susceptible to SARS-CoV-2 infection and long-COVID syndrome appearance. However, there is limited and unclear evidence for long COVID in MHD patients. We collected the general information, symptoms, signs and laboratory indices of 366 MHD patients infected with COVID-19 and conducted 12 months follow-up with a series of questionnaires. As a result, 285 MHD patients had long COVID, with the most common symptoms were fatigue (84.69%) and muscle weakness (72.45%). Mobility problem (p < 0.001), anxiety/depression (p = 0.002) and breathlessness (p < 0.001) were more prevalent in long COVID patients than in non-long COVID patients. Persistent long COVID people were more likely to report all domains problems of the EQ-5D-5L. Age, female, inadequate dialysis (Kt/V < 1.2), coagulation abnormalities (d-dimer > 1 mg/L) and more comorbidities were risk factors for the development of long COVID. In addition to these factors, elevated inflammatory markers (CRP > 10 mg/L) represent an extra risk factor for the persistence of long COVID symptoms in MHD patients. And more than 80% of long COVID symptoms would resolve after 1 year in MHD patients, of which the sixth month after COVID-19 infection is a critical turning point. In conclusion, more than 68% of MHD patients have long COVID, which has a poor impact on their health status and quality of life. These risk factors for the development and persistence of long COVID deserve the attention of clinicians.}, } @article {pmid39298002, year = {2024}, author = {Gupta, MK and Gouda, G and Vadde, R}, title = {Deciphering the role of FOXP4 in long COVID: exploring genetic associations, evolutionary conservation, and drug identification through bioinformatics analysis.}, journal = {Functional & integrative genomics}, volume = {24}, number = {5}, pages = {167}, pmid = {39298002}, issn = {1438-7948}, mesh = {Humans ; *Forkhead Transcription Factors/genetics/metabolism ; *COVID-19/genetics/virology ; *SARS-CoV-2/metabolism/genetics ; Computational Biology/methods ; Evolution, Molecular ; }, abstract = {Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the FOXP4 gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates FOXP4's role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of FOXP4 across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that FOXP4 experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from Streptomyces sp, and Cucurbitacin B from Begonia nantoensis as promising candidates. Overall, our research contributes to understanding how FOXP4 may serve as a therapeutic target for mitigating the impact of LC.}, } @article {pmid39302562, year = {2024}, author = {Varghese, JS and Ali, MK and Guo, Y and Donahoo, WT and Chakkalakal, RJ}, title = {Risk of New-Onset Diabetes Before and During the COVID-19 Pandemic: A Real-World Cohort Study.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {39302562}, issn = {1525-1497}, support = {3R01DK120814-05S1/DK/NIDDK NIH HHS/United States ; P30DK111024/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Studies of new-onset diabetes as a post-acute sequela of SARS-CoV-2 infection are difficult to generalize to all socio-demographic subgroups.

OBJECTIVE: To study the risk of new-onset diabetes after SARS-CoV-2 infection in a socio-demographically diverse sample.

DESIGN: Retrospective cohort study of electronic health record (EHR) data available from the OneFlorida + clinical research network within the National Patient-Centered Clinical Research Network (PCORnet).

SUBJECTS: Persons aged 18 or older were included as part of an Exposed cohort (positive SARS-CoV-2 test or COVID-19 diagnosis between 1 March 2020 and 29 January 2022; n = 43,906), a contemporary unexposed cohort (negative SARS-CoV-2 test; n = 162,683), or an age-sex matched historical control cohort (index visits between 2 Mar 2018 and 30 Jan 2020; n = 40,957).

MAIN MEASURES: The primary outcome was new-onset type 2 diabetes ≥ 30 days after index visit. Hazard ratios and cases per 1000 person-years of new-onset diabetes were studied using target trial approaches for observational data. Associations were reported by sex, race/ethnicity, age, and hospitalization status subgroups.

KEY RESULTS: The sample was 62% female, 21.4% non-Hispanic Black, and 21.4% Hispanic; mean age was 51.8 (SD, 18.9) years. Relative to historical controls (cases, 28.2 [26.0-30.5]), the unexposed (HR, 1.28 [95% CI, 1.18-1.39]; excess cases, [5.1-10.3]), and exposed cohorts (HR, 1.64 [95% CI, 1.50-1.80]; excess cases, 17.3 [13.7-20.8]) had higher risk of new-onset T2DM. Relative to the unexposed cohort, the exposed cohort had a higher risk (HR, 1.28 [1.19-1.37]); excess cases, 9.5 [6.4-12.7]). Findings were similar across subgroups.

CONCLUSION: The pandemic period was associated with increased T2DM cases across all socio-demographic subgroups; the greatest risk was observed among individuals exposed to SARS-CoV-2.}, } @article {pmid39299663, year = {2024}, author = {Hejazian, SS and Sadr, AV and Shahjouei, S and Vemuri, A and Shouhao, Z and Abedi, V and Zand, R}, title = {Prevalence and determinant of long-term Post-COVID conditions among stroke survivors in the United States.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {33}, number = {12}, pages = {108007}, doi = {10.1016/j.jstrokecerebrovasdis.2024.108007}, pmid = {39299663}, issn = {1532-8511}, mesh = {Humans ; Male ; Female ; United States/epidemiology ; *COVID-19/epidemiology ; Prevalence ; Middle Aged ; Cross-Sectional Studies ; Aged ; *Stroke/epidemiology/diagnosis ; Retrospective Studies ; Risk Factors ; Time Factors ; *Survivors ; Adult ; Aged, 80 and over ; Myocardial Infarction/epidemiology ; Risk Assessment ; Behavioral Risk Factor Surveillance System ; Cancer Survivors ; }, abstract = {BACKGROUND: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US.

METHOD: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer.

RESULTS: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6 %, compared to 22.4 %, 29.2 %, and 24.6 % among non-stroke (p < 0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95 %CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95 %CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95 %CI:[1.53-2.92]), and depression (aOR:1.55, 95 %CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95 %CI: [0.41-0.86]).

CONCLUSION: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions.}, } @article {pmid39299642, year = {2024}, author = {Pasculli, P and Zingaropoli, MA and Dominelli, F and Solimini, AG and Masci, GM and Birtolo, LI and Pasquariello, L and Paribeni, F and Iafrate, F and Panebianco, V and Galardo, G and Mancone, M and Catalano, C and Pugliese, F and Palange, P and Mastroianni, CM and Ciardi, MR}, title = {Insights into Long COVID: Unraveling Risk Factors, Clinical Features, Radiological Findings, Functional Sequelae and Correlations: A Retrospective Cohort Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.09.006}, pmid = {39299642}, issn = {1555-7162}, abstract = {BACKGROUND: The long-term symptomatology of COVID-19 has yet to be comprehensively described. The aim of the study was to describe persistent COVID-19 symptoms in a cohort of hospitalized and home-isolated patients.

METHODS: A retrospective cohort study was conducted on long COVID patients. Long COVID symptoms were identified, and patients were divided into hospitalized (in-patients) and home-isolated (out-patients), as well as according to the number of symptoms. Patients were examined by a multidisciplinary medical team. Blood tests, high resolution chest computed tomography (CT), and physical and infectious examinations were performed. Finally, in-patients were evaluated at 2 time-points: on hospital admission (T0) and 3 months after discharge (Tpost).

RESULTS: There were 364 COVID-19 patients enrolled; 82% of patients reported one or more symptoms. The most reported symptom was fatigue. Chest CT showed alteration in 76% of patients, and pulmonary function alterations were observed in 44.7% of patients. A higher risk of presenting at least one symptom was seen in patients treated with corticosteroid, and a higher risk of presenting chest CT residual lesion was observed in hospitalized patients and in patients that received hydroxychloroquine treatment. Moreover, a higher risk of altered pulmonary function was observed in older patients.

CONCLUSION: Long-term sequelae are present in a remarkable number of long COVID patients and pose a new challenge to the health care system to identify long-lasting effects and improve patients' well-being. Multidisciplinary teams are crucial to develop preventive measures, and clinical management strategies.}, } @article {pmid39299386, year = {2024}, author = {Schultz, KR and McGrath, S and Keary, TA and Meng, CK and Batchos, E and Evans, L and Fields, D and Cummings, A and Fornalski, N}, title = {A multidisciplinary approach to assessment and management of long COVID cognitive concerns.}, journal = {Life sciences}, volume = {357}, number = {}, pages = {123068}, doi = {10.1016/j.lfs.2024.123068}, pmid = {39299386}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/complications/psychology/therapy ; *Cognitive Dysfunction/therapy/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Patient Care Team ; Practice Guidelines as Topic ; }, abstract = {Cognitive dysfunction is a commonly reported feature of Long COVID (LC). With the overlap of assessment and treatment for cognitive concerns across multiple disciplines, coupled with current guidelines supporting interdisciplinary care, the aim of this clinically focused article is to provide a review of current guidelines and research related to assessment and interventions to address LC-related cognitive concerns within clinical practice from a multidisciplinary perspective, incorporating best practices for collaboration among Clinical Neuropsychologists, Rehabilitation Psychologists, and Speech-Language Pathologists. Current guidelines for assessment and interventions for cognitive functioning are provided, with clinical suggestions for best practices offered. Additional considerations related to diversity and variable patient presentations are identified. This article provides guidance based on current research and practice standards regarding the utilization of a multidisciplinary, collaborative approach to provide comprehensive assessment and treatment for individuals with LC-related cognitive concerns.}, } @article {pmid39299352, year = {2025}, author = {Marwick, TH and Wexler, N and Smith, J and Wright, L and Ho, F and Oreto, M and Sherriff, AG and Allwood, R and Sata, Y and Manca, S and Howden, E and Huynh, Q}, title = {Cardiac Function and Functional Capacity in Patients With Long COVID: A Comparison to Propensity-Matched Community Controls.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {38}, number = {1}, pages = {16-23.e1}, doi = {10.1016/j.echo.2024.09.006}, pmid = {39299352}, issn = {1097-6795}, mesh = {Humans ; *COVID-19/physiopathology/epidemiology/complications ; Male ; Female ; Middle Aged ; *Echocardiography/methods ; *SARS-CoV-2 ; *Propensity Score ; *Post-Acute COVID-19 Syndrome ; Aged ; Prevalence ; Case-Control Studies ; Risk Factors ; }, abstract = {BACKGROUND: Cardiac impairment has been associated with acute COVID-19 since the earliest reports of the pandemic. However, its role in postacute sequelae of COVID-19 ("long COVID") is undefined, and many existing observations about cardiovascular involvement in postacute sequelae of COVID-19 are uncontrolled.

OBJECTIVE: To compare the prevalence of cardiac dysfunction in patients with long COVID and noninfected controls from the same community and explore their association with functional capacity.

METHODS: Echocardiography was used to assess cardiac structure and function, including the measurement of global longitudinal strain (GLS), in 190 participants with long COVID. All underwent assessment of functional impairment by subjective (Duke Activity Status Index) and objective tests (6-minute walk test). The 190 participants from the long COVID group were matched with those from 979 patients who underwent the same tests in the pre-COVID-19 era, using a propensity score.

RESULTS: The 190 patients with long COVID had similar age and risk factor profiles to those of their matched controls. Left ventricular dimensions and geometry, but not diastolic parameters, were significantly altered in the long COVID group. The long COVID group had subclinical systolic dysfunction (GLS 18.5% ± 2.6% vs 19.3% ± 2.7%, P = .005), and more long COVID patients had abnormal (<16%) GLS (13% vs 8%, P = .035). The association of long COVID with abnormal GLS (odds ratio, 1.49 [1.04, 2.45]) was independent of-and had a similar or greater effect size than-age and risk factors. There was no interaction of long COVID with the association of risk factors with GLS. As expected, the long COVID group had significant subjective (<85% predicted METS; 72% vs 5%, P < .001) and objective functional impairment (29% vs 24%, P = .026), but GLS was only weakly associated with both subjective (r = 0.30, P = .005) and objective (r = 0.21, P = .05) functional impairment. The presence of long COVID was independently associated with subjective (odds ratio = 159.7 [95% CI, 61.6-414.2]) and objective functional impairment (odds ratio = 2.8 [95% CI, 1.5-5.2]).

CONCLUSIONS: Impaired GLS and left ventricular dimensions are the echocardiographic features that are overrepresented in long COVID, and this association is similar to and independent of other risk factors. Impaired GLS is weakly associated with functional impairment.}, } @article {pmid39298620, year = {2024}, author = {Zaremba, S and Miller, AJ and Ovrom, EA and Senefeld, JW and Wiggins, CC and Dominelli, PB and Ganesh, R and Hurt, RT and Bartholmai, BJ and Welch, BT and Ripoll, JG and Joyner, MJ and Ramsook, AH}, title = {Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {137}, number = {5}, pages = {1168-1174}, pmid = {39298620}, issn = {1522-1601}, support = {Postdoctoral Fellowship//Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; F32 HL154320/HL/NHLBI NIH HHS/United States ; R35 HL139854/HL/NHLBI NIH HHS/United States ; 5R35HL139854//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; F32HL154320//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; }, mesh = {Humans ; *COVID-19/physiopathology/complications ; Female ; Male ; Retrospective Studies ; Middle Aged ; Case-Control Studies ; *Bronchi/diagnostic imaging/physiopathology ; *Tomography, X-Ray Computed/methods ; Aged ; Trachea/diagnostic imaging/physiopathology ; SARS-CoV-2 ; Adult ; Lung/diagnostic imaging/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, P > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, P < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.NEW & NOTEWORTHY Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.}, } @article {pmid39296896, year = {2024}, author = {Sperl, L and Stamm, T and Mosor, E and Ritschl, V and Sivan, M and Hoffmann, K and Gantschnig, B}, title = {Translation and cultural adaptation of the COVID-19 Yorkshire Rehabilitation Scale into German.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1401491}, pmid = {39296896}, issn = {2296-858X}, abstract = {BACKGROUND: Experts estimate that in up to 10% of the infected, SARS-CoV-2 would cause persistent symptoms, activity limitations and reduced quality of life. Referred to as long COVID, these conditions might, in the future, specifically impact German-speaking countries due to their higher rates of unvaccinated people compared to other Western countries. Accurate measurement of symptom burden and its consequences is needed to manage conditions such as long COVID, and several tools have been developed to do so. However, no patient-reported instrument existed in the German language at the time of writing.

OBJECTIVE: This study, therefore, aimed to develop a German version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS).

METHODS: We conducted a translation and qualitative evaluation, including cultural adaptation, of the C19-YRS and assessed its face validity. After creating a preliminary version, 26 individuals (14 women [53%]) participated in cognitive interviews (January 2022 to March 2022). Using cognitive debriefing interviews, we ensured the content's comprehensibility. The matrix-framework method guided the qualitative data analysis.

RESULTS: Compared to the original English version, adaptations were necessary, resulting in changes to the introductory text, while the items for recording persistent symptoms were hardly changed.

CONCLUSION: The German version of the C19-YRS is expected to support standardized long COVID care.}, } @article {pmid39296584, year = {2024}, author = {Camporesi, A and Morello, R and La Rocca, A and Zampino, G and Vezzulli, F and Munblit, D and Raffaelli, F and Valentini, P and Buonsenso, D}, title = {Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study.}, journal = {EClinicalMedicine}, volume = {76}, number = {}, pages = {102815}, pmid = {39296584}, issn = {2589-5370}, abstract = {BACKGROUND: Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases.

METHODS: Children aged 0-18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection.

FINDINGS: 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P < 0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P = 0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P < 0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P < 0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P = 0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P = 0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P < 0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P = 0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection.

INTERPRETATION: This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics.

FUNDING: This study has been funde by Pfizer non-competitive grant, granted to DB (#65925795).}, } @article {pmid39294767, year = {2024}, author = {León-Herrera, S and Oliván-Blázquez, B and Sánchez-Recio, R and Méndez-López, F and Magallón-Botaya, R and Sánchez-Arizcuren, R}, title = {Effectiveness of an online multimodal rehabilitation program in long COVID patients: a randomized clinical trial.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {82}, number = {1}, pages = {159}, pmid = {39294767}, issn = {0778-7367}, support = {PI21/01356//Instituto de Salud Carlos III/ ; }, abstract = {BACKGROUND: Digital interventions are expected to facilitate the treatment of patients suffering from Long COVID. This trial assesses the effectiveness of a multimodal rehabilitation program -comprising both online and synchronous components- in managing the characteristic symptoms of Long COVID and, consequently, in improving quality of life. It also aims to identify which changes in measured variables from baseline (T0) to post-intervention (T1) predict an improvement in quality of life.

METHODS: A blind randomized controlled trial was conducted with two parallel groups: (1) the control group, which received usual treatment from the primary care physician and (2) the intervention group, which received usual treatment in addition to an online multimodal rehabilitation program. The data were collected at two time points: prior to the start of the intervention and three months after it. The main outcome variable was quality of life, encompassing both mental health and physical health-related quality of life. Sociodemographic and clinical variables were collected as secondary variables.

RESULTS: A total of 134 participants (age 48.97 ± 7.64; 84.33% female) were included and randomized into the control group (67 participants) and the intervention group (67 participants). Comparative analyses conducted before and after the intervention showed a significant improvement in the mental health-related quality of life of the participants who received the intervention, with a mean increase of 1.98 points (p < 0.05). Linear regression analyses revealed that both received the intervention (b = 3.193; p < 0.05) and an increased self-efficacy (b = 0.298; p < 0.05) were predictors of greater improvement in mental health-related quality of life.}, } @article {pmid39294567, year = {2024}, author = {Moniz, M and Ruivinho, C and Goes, AR and Soares, P and Leite, A}, title = {Long COVID is not the same for everyone: a hierarchical cluster analysis of Long COVID symptoms 9 and 12 months after SARS-CoV-2 test.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1001}, pmid = {39294567}, issn = {1471-2334}, support = {2020.09525.BD//Fundação para a Ciência e a Tecnologia/ ; CEECINST/00049/2021/CP2817/CT0001//Fundação para a Ciência e a Tecnologia/ ; UIDP/04923/2020//Comprehensive Health Research Center/ ; UIDP/04923/2020//Comprehensive Health Research Center/ ; UIDP/04923/2020//Comprehensive Health Research Center/ ; UIDP/04923/2020//Comprehensive Health Research Center/ ; UIDP/04923/2020//Comprehensive Health Research Center/ ; }, mesh = {Humans ; Female ; Middle Aged ; *COVID-19/epidemiology/diagnosis ; Male ; Cross-Sectional Studies ; Adult ; Cluster Analysis ; *SARS-CoV-2/genetics ; *Post-Acute COVID-19 Syndrome ; Portugal/epidemiology ; Aged ; COVID-19 Testing/methods ; }, abstract = {BACKGROUND: Identifying symptom clusters in Long COVID is necessary for developing effective therapies for this diverse condition and improving the quality of life of those affected by this heterogeneous condition. In this study, we aimed to identify and compare symptom clusters at 9 and 12 months after a SARS-CoV-2 positive test and describe each cluster regarding factors at infection.

METHODS: This is a cross-sectional study with individuals randomly selected from the Portuguese National System of Epidemiological Surveillance (SINAVE) database. Individuals who had a positive RT-PCR SARS-CoV-2 test in August 2022 were contacted to participate in a telephonic interview approximately 9 and 12 months after the test. A hierarchical clustering analysis was performed, using Euclidean distance and Ward's linkage. Clustering was performed in the 35 symptoms reported 9 and 12 months after the SARS-CoV-2 positive test and characterised considering age, sex, pre-existing health conditions and symptoms at time of SARS-CoV-2 infection.

RESULTS: 552 individuals were included at 9 months and 458 at 12 months. The median age was 52 years (IQR: 40-64 years) and 59% were female. Hypertension and high cholesterol were the most frequently reported pre-existing health conditions. Memory loss, fatigue or weakness and joint pain were the most frequent symptoms reported 9 and 12 months after the positive test. Four clusters were identified at both times: no or minor symptoms; multi-symptoms; joint pain; and neurocognitive-related symptoms. Clusters remained similar in both times, but, within the neurocognitive cluster, memory loss and concentration issues increased in frequency at 12 months. Multi-symptoms cluster had older people, more females and more pre-existing health conditions at 9 months. However, at 12 months, older people and those with more pre-existing health conditions were in joint pain cluster.

CONCLUSIONS: Our results suggest that Long COVID is not the same for everyone. In our study, clusters remained similar at 9 and 12 months, except for a slight variation in the frequency of symptoms that composed each cluster. Understanding Long COVID clusters might help identify treatments for this condition. However, further validation of the observed clusters and analysis of its risk factors is needed.}, } @article {pmid39293561, year = {2025}, author = {Romanowska-Kocejko, M and Braczko, A and Jędrzejewska, A and Żarczyńska-Buchowiecka, M and Kocejko, T and Kutryb-Zając, B and Hellmann, M}, title = {Follow-up assessment of the microvascular function in patients with long COVID.}, journal = {Microvascular research}, volume = {157}, number = {}, pages = {104748}, doi = {10.1016/j.mvr.2024.104748}, pmid = {39293561}, issn = {1095-9319}, mesh = {Humans ; *Microcirculation ; Male ; Female ; *COVID-19/blood/physiopathology/diagnosis/complications ; Middle Aged ; Aged ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Time Factors ; Hypoxia-Inducible Factor 1, alpha Subunit/blood ; Follow-Up Studies ; Skin/blood supply ; Biomarkers/blood ; Arginine/blood/analogs & derivatives ; SARS-CoV-2 ; Microvessels/physiopathology ; COVID-19 Drug Treatment ; Adult ; }, abstract = {Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microvascular function was assessed in long COVID patients (n = 33) and healthy controls (n = 30) using flow-mediated skin fluorescence technique (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Microcirculatory function readings were taken twice, 3 months apart. In addition, we quantified biochemical markers such as the serum L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) to assess their relation with microvascular parameters evaluated in vivo. In patients with long COVID, serum HIF1α was significantly correlated to IRindex (r = -0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HRmax (r = -0.343, p < 0.05) and HRindex (r = -0.335, p < 0.05). The IR parameters were found lower or negative in long COVID patients and recovered in three-month follow-up. Hypoxia sensitivity value was significantly higher in long COVID patients examined after three months of treatment based on the combination of ACE-inhibitors and beta-adrenolytic compared to baseline condition (85.2 ± 73.8 vs. 39.9 ± 51.7 respectively, p = 0.009). This study provides evidence that FMSF is a sensitive, non-invasive technique to track changes in microvascular function that was impaired in long COVID and recovered after 3 months, especially in patients receiving a cardioprotective therapy.}, } @article {pmid39293298, year = {2024}, author = {Pry, JM and McCullough, K and Lai, KW and Lim, E and Mehrotra, ML and Lamba, K and Jain, S}, title = {Defining long COVID using a population-based SARS-CoV-2 survey in California.}, journal = {Vaccine}, volume = {42}, number = {26}, pages = {126358}, doi = {10.1016/j.vaccine.2024.126358}, pmid = {39293298}, issn = {1873-2518}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; California/epidemiology ; Female ; Male ; Middle Aged ; Adult ; Cross-Sectional Studies ; Adolescent ; Young Adult ; *SARS-CoV-2/immunology ; Prevalence ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Aged ; COVID-19 Vaccines/administration & dosage ; }, abstract = {BACKGROUND: More than four years after the start of the COVID-19 pandemic, understanding of SARS-CoV-2 burden and post-acute sequela of COVID (PASC), or long COVID, continues to evolve. However, prevalence estimates are disparate and uncertain. Leveraging survey responses from a large serosurveillance study, we assess prevalence estimates using five different long COVID definitions among California residents.

METHODS: The California Department of Public Health (CDPH) conducted a cross-sectional survey that included questions about acute COVID-19 infection and recovery. A random selection of California households was invited to participate in a survey that included demographic information, clinical symptoms, and COVID-19 vaccination history. We assessed prevalence and predictors of long COVID among those previously testing positive for SARS-CoV-2 across different definitions using logistic regression.

FINDINGS: A total of 2883 participants were included in this analysis; the majority identified as female (62.5 %), and the median age was 39 years (interquartile range: 17-55 years). We found a significant difference in long COVID prevalence across definitions with the highest prevalence observed when participants were asked about incomplete recovery (20.9 %, 95 % confidence interval [CI]: 19.4-22.5) and the lowest prevalence was associated with severe long COVID affecting an estimated 4.9 % (95 % CI 4.1-5.7) of the participant population. Individuals that completed the primary vaccination series had significantly lower prevalence of long COVID compared to those that did not receive COVID vaccination.

INTERPRETATION: There were significant differences in the estimated prevalence of long COVID across different definitions. People who experience a severe initial COVID-19 infection should be considered at a higher probability for developing long COVID.

FUNDING: Centers for Disease Control and Prevention - Epidemiology and Laboratory Capacity.}, } @article {pmid39291997, year = {2024}, author = {Pang, Z and Tang, A and He, Y and Fan, J and Yang, Q and Tong, Y and Fan, H}, title = {Neurological complications caused by SARS-CoV-2.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {4}, pages = {e0013124}, pmid = {39291997}, issn = {1098-6618}, support = {82202492//MOST | National Natural Science Foundation of China (NSFC)/ ; 2020YFA0712102//MOST | National Key Research and Development Program of China (NKPs)/ ; QNTD2023-01//MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities)/ ; 2023BINCMCF28//Nutrition and Care of Maternal & Child Research Project of Biotime Institute of Nutrition & Care/ ; }, mesh = {Humans ; Central Nervous System/virology/pathology ; *COVID-19/complications/virology ; *Nervous System Diseases/pathology/virology ; *SARS-CoV-2/pathogenicity ; }, abstract = {SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.}, } @article {pmid39290777, year = {2024}, author = {Swift, MD and Breeher, LE and Dierkhising, R and Hickman, J and Johnson, MG and Roellinger, DL and Virk, A}, title = {Association of COVID-19 Vaccination With Risk of Medically Attended Postacute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae495}, pmid = {39290777}, issn = {2328-8957}, abstract = {BACKGROUND: Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent postacute sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies based on symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings.

METHODS: In this retrospective cohort of patients with an initial SARS-CoV-2 infection who were continually empaneled for primary care in a large US health system, the electronic health record was queried for preinfection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection and between vaccination status and hospitalization for SARS-CoV-2 infection.

RESULTS: During the observation period, 6.9% of patients experienced medically attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients and those vaccinated with either 2 doses of an mRNA vaccine or >2 doses.

CONCLUSIONS: We found no association between vaccination status at the time of infection and development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.}, } @article {pmid39289865, year = {2024}, author = {Parums, DV}, title = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and the Urgent Need to Identify Diagnostic Biomarkers and Risk Factors.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {30}, number = {}, pages = {e946512}, pmid = {39289865}, issn = {1643-3750}, mesh = {Humans ; *Biomarkers/blood ; Cognitive Dysfunction/blood/diagnosis/immunology/virology ; *COVID-19/complications/immunology/virology ; Dyspnea/blood/diagnosis/immunology/virology ; Fatigue/blood/diagnosis/immunology/virology ; *Post-Acute COVID-19 Syndrome/blood/diagnosis/immunology/virology ; Risk Factors ; SARS-CoV-2/immunology/pathogenicity ; }, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.}, } @article {pmid39287394, year = {2024}, author = {Johnson, SG and Abedian, S and Stürmer, T and Huling, JD and Lewis V, C and Buse, JB and Brosnahan, SB and Mudumbi, PC and Erlandson, KM and McComsey, GA and Arnold, J and Wiggen, TD and Wong, R and Murphy, S and Rosen, C and Kaushal, R and Weiner, MG and Bramante, C and , }, title = {Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program.}, journal = {Diabetes care}, volume = {47}, number = {11}, pages = {1930-1940}, pmid = {39287394}, issn = {1935-5548}, support = {P30DK124723//NC Diabetes Research Center/ ; K23 DK124654/DK/NIDDK NIH HHS/United States ; OT2HL16184701/HL/NHLBI NIH HHS/United States ; AG056479/AG/NIA NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; P30 DK124723/DK/NIDDK NIH HHS/United States ; R01 AG056479/AG/NIA NIH HHS/United States ; DK124654/DK/NIDDK NIH HHS/United States ; UM1TR004406/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Metformin/therapeutic use ; *COVID-19/epidemiology/mortality ; *Diabetes Mellitus, Type 2/drug therapy/epidemiology ; Female ; Male ; Middle Aged ; Retrospective Studies ; *Electronic Health Records ; Aged ; *Hypoglycemic Agents/therapeutic use ; Incidence ; Adult ; SARS-CoV-2 ; Cohort Studies ; }, abstract = {OBJECTIVE: Studies show metformin use before and during SARS-CoV-2 infection reduces severe COVID-19 and postacute sequelae of SARS-CoV-2 (PASC) in adults. Our objective was to describe the incidence of PASC and possible associations with prevalent metformin use in adults with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS: This is a retrospective cohort analysis using the National COVID Cohort Collaborative (N3C) and Patient-Centered Clinical Research Network (PCORnet) electronic health record (EHR) databases with an active comparator design that examined metformin-exposed individuals versus nonmetformin-exposed individuals who were taking other diabetes medications. T2DM was defined by HbA1c ≥6.5 or T2DM EHR diagnosis code. The outcome was death or PASC within 6 months, defined by EHR code or computable phenotype.

RESULTS: In the N3C, the hazard ratio (HR) for death or PASC with a U09.9 diagnosis code (PASC-U09.0) was 0.79 (95% CI 0.71-0.88; P < 0.001), and for death or N3C computable phenotype PASC (PASC-N3C) was 0.85 (95% CI 0.78-0.92; P < 0.001). In PCORnet, the HR for death or PASC-U09.9 was 0.87 (95% CI 0.66-1.14; P = 0.08), and for death or PCORnet computable phenotype PASC (PASC-PCORnet) was 1.04 (95% CI 0.97-1.11; P = 0.58). Incident PASC by diagnosis code was 1.6% metformin vs. 2.0% comparator in the N3C, and 2.1% metformin vs. 2.5% comparator in PCORnet. By computable phenotype, incidence was 4.8% metformin and 5.2% comparator in the N3C and 24.7% metformin vs. 26.1% comparator in PCORnet.

CONCLUSIONS: Prevalent metformin use is associated with a slightly lower incidence of death or PASC after SARS-CoV-2 infection. PASC incidence by computable phenotype is higher than by EHR code, especially in PCORnet. These data are consistent with other observational analyses showing prevalent metformin is associated with favorable outcomes after SARS-CoV-2 infection in adults with T2DM.}, } @article {pmid39287023, year = {2024}, author = {Scheithauer, TPM and Montijn, RC and Mieremet, A}, title = {Gut microbe-host interactions in post-COVID syndrome: a debilitating or restorative partnership?.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402544}, pmid = {39287023}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/microbiology/virology ; *Post-Acute COVID-19 Syndrome ; *Host Microbial Interactions ; *Probiotics/therapeutic use ; *SARS-CoV-2/physiology ; Brain-Gut Axis/physiology ; Animals ; Dysbiosis/microbiology ; Lung/microbiology/virology ; }, abstract = {Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.}, } @article {pmid39285602, year = {2024}, author = {Lenning, OB and Jonsson, G and Grimstad, T and Janssen, EAM and Braut, GS and Berven, F and Omdal, R}, title = {No signs of mast cell involvement in long-COVID: A case-control study.}, journal = {Scandinavian journal of immunology}, volume = {100}, number = {5}, pages = {e13407}, doi = {10.1111/sji.13407}, pmid = {39285602}, issn = {1365-3083}, support = {SDAM_HEL45920//EkstraStiftelsen Helse og Rehabilitering (Stiftelsen Dam)/ ; //Norwegian Brain Council/ ; }, mesh = {Humans ; *Mast Cells/immunology ; *COVID-19/immunology/blood ; Male ; Case-Control Studies ; Female ; Middle Aged ; *Tryptases/blood ; *SARS-CoV-2/immunology ; Adult ; Aged ; *Carboxypeptidases A/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID caused by SARS-CoV-2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells-evolutionary old "multipurpose" innate immune cells-was reported recently in studies of acute infection and post-acute-COVID-19 syndrome. Mast cell activity has been suggested in long-COVID. In this case-control study, we compared data from 24 individuals with long-COVID (according to the NICE criteria) and 24 age- and sex-matched healthy individuals with a history of SARS-CoV-2 infection without developing sequelae. Serum levels of the proteases beta-tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance. TPSB2 and CPA3 levels were median (range) 26.9 (2.0-1000) and 5.8 (1.5-14.0) ng/mL, respectively, in the long-COVID group. The corresponding values in the control group were 10.9 (2.0-1000) (p = 0.93) and 5.3 (3.5-12.9) ng/mL (p = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF-36, 3.1-3.10 were revealed. We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long-COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long-term pathogenesis of long-COVID, at least in the majority of patients.}, } @article {pmid39285080, year = {2024}, author = {Janko, RK and Haussmann, I and Patel, A}, title = {A Longitudinal Investigation of the Prevalence and Incidence of Self-Reported COVID-19 Disease and the Pandemic's Impact Among Seventh-day Adventist and Non-Adventists Living in the UK.}, journal = {Journal of religion and health}, volume = {}, number = {}, pages = {}, pmid = {39285080}, issn = {1573-6571}, abstract = {This research investigated the prevalence and incidence of COVID-19 infection among Seventh-day Adventist Christians in the UK compared to non-Adventists and assessed the pandemic's impact on their health and dietary intake. Seventh-day Adventists and non-Adventists in the UK completed an online survey, including a Food Frequency Questionnaire, a 24-h dietary recall, and health and lifestyle questions. Participants were followed for 2 years to determine COVID-19 incidence rates. The baseline survey was completed by 170 people, 86 of whom were Adventists. The follow-up at 2 years showed a significantly lower self-reported COVID-19 incidence among Adventists (OR 0.45, 95% CI 0.2, 1.0, p = 0.05). The incidence rate among Adventists was 65.48 per 1000 person-years versus 121.79 per 1000 person-years among non-Adventists. Adventists were less likely to experience long COVID (OR 0.30, 95% CI 0.12, 0.78, p = 0.01). Despite being older, Adventists had a significantly lower COVID-19 incidence rate. The Adventist lifestyle, including healthy eating habits, fasting, a plant-based diet, and abstaining from alcohol and coffee, was prevalent in this sample. More research is needed to explore the association between the Adventist lifestyle and infectious disease.}, } @article {pmid39284068, year = {2024}, author = {Rowntree, LC and Audsley, J and Allen, LF and McQuilten, HA and Hagen, RR and Chaurasia, P and Petersen, J and Littler, DR and Tan, HX and Murdiyarso, L and Habel, JR and Foo, IJH and Zhang, W and Ten Berge, ERV and Ganesh, H and Kaewpreedee, P and Lee, KWK and Cheng, SMS and Kwok, JSY and Jayasinghe, D and Gras, S and Juno, JA and Wheatley, AK and Kent, SJ and Rossjohn, J and Cheng, AC and Kotsimbos, TC and Trubiano, JA and Holmes, NE and Pang Chan, KK and Hui, DSC and Peiris, M and Poon, LLM and Lewin, SR and Doherty, PC and Thevarajan, I and Valkenburg, SA and Kedzierska, K and Nguyen, THO}, title = {SARS-CoV-2-specific CD8[+] T cells from people with long COVID establish and maintain effector phenotype and key TCR signatures over 2 years.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {39}, pages = {e2411428121}, pmid = {39284068}, issn = {1091-6490}, support = {1173871//DHAC | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Humans ; *CD8-Positive T-Lymphocytes/immunology ; *SARS-CoV-2/immunology ; *COVID-19/immunology ; *Receptors, Antigen, T-Cell/immunology/metabolism ; Epitopes, T-Lymphocyte/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Middle Aged ; Male ; Female ; Post-Acute COVID-19 Syndrome ; Phenotype ; B-Lymphocytes/immunology ; Immunologic Memory/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; Aged ; }, abstract = {Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8[+] and CD4[+] T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a- and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8[+] and CD4[+] T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8[+] T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID.}, } @article {pmid39283441, year = {2024}, author = {Zeigler, Z and Acevedo, A}, title = {Obesity, Physical Activity, and COVID-19.}, journal = {Advances in experimental medicine and biology}, volume = {1457}, number = {}, pages = {431-446}, doi = {10.1007/978-3-031-61939-7_24}, pmid = {39283441}, issn = {0065-2598}, mesh = {*COVID-19/epidemiology/prevention & control ; Humans ; *Obesity/epidemiology/physiopathology ; *Exercise ; *Sedentary Behavior ; *SARS-CoV-2 ; Risk Factors ; Comorbidity ; }, abstract = {Estimates suggest that over 80% of people with COVID-19 may experience mild to no symptoms. The Centers for Disease Control and Prevention (CDC) reported that around 7-8% of positive COVID-19 cases were hospitalized in the first year of the pandemic. A substantial body of evidence points to obesity, sedentary behavior, and low physical activity levels as risk factors for susceptibility to the virus and the severity of symptoms. Obese individuals are 46% more likely to contract the virus than those of normal weight, and those who are physically active have an 11% reduced risk of contracting the virus. Medical experts have also identified obesity, sedentary behavior, and physical inactivity as risk factors for severe COVID-19 symptoms and long COVID. Evidence from bariatric surgery suggests that weight loss decreases the susceptibility and severity of COVID-19. The mechanisms linking obesity, sedentary behavior, and physical activity to COVID-19 are somewhat similar. Obesity, sedentary behavior, and low physical activity are all linked to inflammation, immune dysfunction, and comorbidities such as diabetes and cardiovascular disease that increase COVID-19 risk. Additionally, achieving the recommended 150 min of moderate-intensity exercise seems to be the desired dose for protection from COVID-19.}, } @article {pmid39283425, year = {2024}, author = {Celeghin, A and Stanziano, M and Palermo, S}, title = {Addressing Long COVID Sequelae and Neurocovid: Neuropsychological Scenarios and Neuroimaging Findings.}, journal = {Advances in experimental medicine and biology}, volume = {1457}, number = {}, pages = {143-164}, pmid = {39283425}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/psychology/complications ; *Neuroimaging/methods ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/diagnostic imaging/physiopathology/psychology ; Quality of Life ; Brain/diagnostic imaging/physiopathology ; Neuropsychological Tests ; }, abstract = {In the face of increasing reports of CNS involvement in COVID-19 cases, it is likely that the current epidemic may be accompanied by a significant increase in the prevalence of neurological sequelae, cognitive dysfunction, and long-term behavioural alterations affecting quality of life and autonomy in daily life. This is consequential to the neuroinvasion and multi-organ dysfunction, but also to the psychological distress and socioeconomic changes that occur. Long COVID and neurocovid are now an established concept worldwide. However, the clinical features of these two entities are still debated. The chapter provides information about the nosographic framing, associated pathophysiological mechanisms, alterations in the central and peripheral nervous systems, and the associated neurocognitive profile, indications about predictor and clinical evaluation according to a patient-centred multidimensional immuno-behavioural approach.}, } @article {pmid39283418, year = {2024}, author = {Yazdanpanah, N and Sedikides, C and Ochs, HD and Camargo, CA and Darmstadt, GL and Cerda, A and Cauda, V and Peters, GJ and Sellke, F and Wong, ND and Comini, E and Jimeno, AR and Glover, V and Hatziargyriou, N and Vincenot, CE and Bordas, SPA and Rao, IM and Abolhassani, H and Gharehpetian, GB and Weiskirchen, R and Gupta, M and Chandel, SS and Olusanya, BO and Cheson, B and Pomponio, A and Tanzer, M and Myles, PS and Ma, WX and Bella, F and Ghavami, S and Moein Moghimi, S and Pratico, D and Hernandez, AM and Martinez-Urbistondo, M and Urbistondo, DM and Fereshtehnejad, SM and Ali, I and Kimura, S and Wallace Hayes, A and Cai, W and Ernest, CKJ and Thomas, S and Rahimi, K and Sorooshian, A and Schreiber, M and Kato, K and Luong, JHT and Pluchino, S and Lozano, AM and Seymour, JF and Kosik, KS and Hofmann, SG and McIntyre, RS and Perc, M and Leemans, A and Klein, RS and Ogino, S and Wlezien, C and Perry, G and Nieto, JJ and Levin, L and Klionsky, DJ and Mobasher, B and Dorigo, T and Rezaei, N and , }, title = {Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.}, journal = {Advances in experimental medicine and biology}, volume = {1457}, number = {}, pages = {1-31}, pmid = {39283418}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control/transmission ; *Global Health/economics/statistics & numerical data ; *Pandemics/economics/prevention & control/statistics & numerical data ; }, abstract = {Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community.}, } @article {pmid39282763, year = {2024}, author = {Silva, MMD and Benites, MN and Castro, YM and Moura, PV and Zhang, L}, title = {Prevalence of symptoms of post-COVID-19 condition (long COVID) in children hospitalized with COVID-19: A systematic review of observational studies.}, journal = {Pediatric pulmonology}, volume = {59}, number = {12}, pages = {3159-3169}, doi = {10.1002/ppul.27257}, pmid = {39282763}, issn = {1099-0496}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Child ; Prevalence ; *Observational Studies as Topic ; *Hospitalization/statistics & numerical data ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Adolescent ; Child, Preschool ; }, abstract = {This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I[2] = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I[2] = 0%), psychological disorders (10%, 95% CI: 1%-25%, I[2] = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I[2] = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I[2] = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I[2] = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.}, } @article {pmid39280695, year = {2024}, author = {Schaustz, EB and Secco, JCP and Barroso, JM and Ferreira, JR and Tortelly, MB and Pimentel, AL and Figueiredo, ACBS and Albuquerque, DC and Sales, ARK and Rosado de-Castro, PH and Pinheiro, MVT and Souza, OF and Medei, E and Luiz, RR and Silvestre-Sousa, A and Camargo, GC and Moll-Bernardes, R}, title = {Cardiac remodeling and inflammation detected by magnetic resonance imaging in COVID-19 survivors.}, journal = {International journal of cardiology. Heart & vasculature}, volume = {54}, number = {}, pages = {101499}, pmid = {39280695}, issn = {2352-9067}, abstract = {BACKGROUND: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19.

METHODS: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity.

RESULTS: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced.

CONCLUSION: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high.}, } @article {pmid39280382, year = {2024}, author = {Jatiya, L and Marie Feula, J and R, L and R, V and Rajesh, J}, title = {Autonomic Imbalance and Elevated Inflammatory Cytokines in Long COVID: A Cross-Sectional Study.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66971}, pmid = {39280382}, issn = {2168-8184}, abstract = {INTRODUCTION: Following an infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), many individuals fully recover. On the other hand, a few have symptoms that last for weeks, months, or even years after their initial diagnosis. Symptoms of COVID-19 persisting for four weeks and more are termed long COVID.

AIM: To assess the long-term cardiovascular morbidity by battery of cardiac autonomic function tests as well as the persistence of inflammation in COVID-recovered patients three months after initial infection.  Methodology: 150 patients were selected who had recovered from COVID-19 at least three months prior to the study. After obtaining informed written consent, a throat swab was tested for COVID-19, and those with negative reverse transcription polymerase chain reaction (RT-PCR) results were subjected to autonomic function testing. Serum interleukin-6 and C-reactive protein levels were determined by enzyme-linked immunosorbent assay (ELISA) test.

RESULTS: Out of 150 subjects 36 were found to have autonomic dysfunction graded according to Ewing's criteria. Individuals with autonomic dysfunction also had significantly increased inflammatory biomarker levels. There was also significant correlation between inflammatory markers and autonomic function test and heart rate variability parameters.

CONCLUSION: Even years after the COVID-19 pandemic was declared, new symptom patterns and syndromes such as 'long COVID' are appearing. A better understanding of the pathophysiological mechanisms of post-COVID manifestations that affect the autonomic nervous system, as well as customized therapeutic care, should help reduce COVID-19 sequelae, particularly if we act early in the disease.}, } @article {pmid39277496, year = {2024}, author = {van der Feltz-Cornelis, CM and Turk, F and Sweetman, J and Khunti, K and Gabbay, M and Shepherd, J and Montgomery, H and Strain, WD and Lip, GYH and Wootton, D and Watkins, CL and Cuthbertson, DJ and Williams, N and Banerjee, A}, title = {Corrigendum to "Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis" [General Hospital Psychiatry volume 88 (2024)10-22 10.1016/j.genhosppsych.2024.02.009].}, journal = {General hospital psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.genhosppsych.2024.09.006}, pmid = {39277496}, issn = {1873-7714}, } @article {pmid39276663, year = {2024}, author = {Furlanis, G and Buoite Stella, A and Torresin, G and Michelutti, M and Ajčević, M and Manganotti, P}, title = {Neurological long-COVID: Associations among fatigue, dysautonomia, depression, and subjective memory complaints.}, journal = {Clinical neurology and neurosurgery}, volume = {246}, number = {}, pages = {108522}, doi = {10.1016/j.clineuro.2024.108522}, pmid = {39276663}, issn = {1872-6968}, mesh = {Humans ; *Fatigue/etiology/psychology/epidemiology ; Male ; Female ; Middle Aged ; *Depression/psychology/epidemiology ; *COVID-19/complications/psychology ; *Primary Dysautonomias/complications ; *Memory Disorders/psychology ; Adult ; *Post-Acute COVID-19 Syndrome ; Aged ; Surveys and Questionnaires ; Cognitive Dysfunction/psychology ; }, abstract = {INTRODUCTION: Long-COVID is a multisystem disease characterized by a varied presentation of symptoms. According to most recent research, the most common symptom of long-COVID is fatigue, which up to this date lacks a universally accepted definition. This study aimed to investigate neurocognitive and physical manifestations of neurological long-COVID, particularly fatigue and its relation with autonomic disfunction, cognitive impairment (known as, brain fog), and depressive symptoms. Furthermore, the study provided insights into predictors of fatigue in long-COVID.

METHODS: The included patients (n=141) were referred to the neuro-long-COVID ambulatory service of Trieste from 30 September 2021-02 March 2022. Patients were given self-reporting questionnaires to screen for fatigue, autonomic dysfunction, cognitive impairment and depressive symptoms. The questionnaires adopted for these conditions to be assessed were Fatigue Severity Scale (FSS), COMPASS-31, Prospective-Retrospective Memory Questionnaire (PRMQ), and Beck Depression Inventory (BDI). Participants were divided into two groups, fatigued and non-fatigued patients, based on FSS scoring (scores > 4.67 indicate fatigued patients). The questionnaire scores of the two groups were then compared.

RESULTS: Fatigued patients had significantly higher scores in COMPASS (p<0.001, Cohen's d=1.077), BDI (p<0.001, Cohen's d=0.862), and PRMQ (p<0.001, Cohen's d=1.159). Furthermore, the multivariate regression analysis showed that predictors of fatigue in long-COVID were symptomatological burden in acute infection (OR=1.38, 95 % CI 1.020-1.887, p=0.037) and in long-COVID (OR=1.78, 95 % CI 1.133-2.2824, p=0.013), COMPASS-31>16 (OR=3.44, 95 % CI 1240-9.560, p=0.018) and BDI>15 (OR=5.1, 95 % CI 1.715-15.164, p=0.003).

CONCLUSION: This study showed associations between fatigue, dysautonomia and depression, as well as with symptom burden in acute and long-COVID.}, } @article {pmid39274232, year = {2024}, author = {Baba, K and Kawai, S and Iwase, S and Ushida, T and Tamura, Y and Arimoto, M and Nojiri, M and Watanabe, D and Ban, N}, title = {Symptoms, Course, and Factors Related to Long-Term Morbidity, Including Differences between Infection Strains, in Patients with Long COVID in a Primary Care Clinic in Japan: An Observational Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {17}, pages = {}, pmid = {39274232}, issn = {2077-0383}, abstract = {Objectives: The objectives were to investigate the clinical characteristics and course of long COVID, defined as the persistence of symptoms at least one month after the onset of COVID-19, in outpatients and to clarify differences in symptoms between SARS CoV-2 mutant strains. Methods: Our observational study in a primary care institution in Japan included 1053 patients with long COVID who visited our outpatient clinic between April 2021 and March 2023. Symptom distribution, performance status, and patient background at the time of the first outpatient visit were compared between infectious strains (Delta and before group and Omicron group). Background factors and symptoms related to time to remission were also analyzed. Results: The severity of COVID-19 in the acute phase was mild, moderate, and severe in 82.2%, 14.9%, and 2.9% in the Delta and before group; and in 97.6%, 1.7%, and 0.4% in the Omicron group, respectively. Vaccination coverage was significantly different between the Delta and before (37.1%) and Omicron groups (73.1%) (p < 0.001), probably due to the period of vaccine unavailability in the former group. Symptoms of fatigue and headache occurred most frequently, irrespective of infectious strain. The mean number of symptoms per patient was significantly higher in the Delta and before group than the Omicron group (3.4 vs. 2.7, p < 0.0001). The median time overall to remission of long COVID was 169 days. Cox hazard model analysis identified female sex, high body mass index, and dyspnea (but not infectious strain) as significant factors prolonging the time to remission (p < 0.05). Conclusions: Differences in the number of symptoms between infectious strains may be related to differences in viral virulence and/or vaccination coverage. However, the clinical course was found to be minimally influenced by the infectious strain. The present results should improve the understanding of prognosis in patients with long COVID from both the clinical and social perspectives.}, } @article {pmid39274228, year = {2024}, author = {Duraníková, O and Horváthová, S and Sabaka, P and Minár, M and Boleková, V and Straka, I and Valkovič, P}, title = {Prevalence and Risk Factors of Headache Associated with COVID-19.}, journal = {Journal of clinical medicine}, volume = {13}, number = {17}, pages = {}, pmid = {39274228}, issn = {2077-0383}, support = {VEGA 2/0076/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; }, abstract = {Background: Headache is a prevalent and disabling non-respiratory symptom of COVID-19, posing a persistent challenge in post-COVID syndrome. This study aimed to determine the prevalence, phenotypes, risk factors and biomarkers associated with COVID-related headaches. Methods: A retrospective analysis of 634 hospitalized COVID-19 patients was conducted, with 295 participants being followed up 12-15 months post-discharge via telephone call. Initial laboratory workups, including complete blood count and various biochemical parameters, were compared between headache and non-headache groups. Results: One-third of hospitalized patients experienced headaches, predominantly younger individuals (p < 0.001) and women (p = 0.002). Non-dominant headaches were characterized as dull (56.9%) and holocranial (26.5%), while dominant headaches were unilateral (31.3%) with photophobia (34.3%) and nausea (56.3%). Persistent headaches were unilateral (40%) and pulsating (38%) with phonophobia (74%). Decreased CD4 T cells independently predicted COVID-associated headaches, with elevated IL-6 levels noted in the dominant-headache group (p = 0.040). Remarkably, 50% of patients reported persistent headaches 12-15 months post-infection. Dexamethasone administration significantly reduced the likelihood of long-COVID headaches (52% vs. 73%, p = 0.029). Conclusions: Headache was present in one-third of patients with heterogenous phenotypes: tension headache in the non-dominant group, and migraine in the dominant and persistent headache groups. Persistent headache remains a challenge, with dexamethasone showing potential in reducing its incidence, emphasizing the need for tailored approaches in managing long-COVID headaches.}, } @article {pmid39273608, year = {2024}, author = {Santana-de Anda, K and Torres-Ruiz, J and Mejía-Domínguez, NR and Alcalá-Carmona, B and Maravillas-Montero, JL and Páez-Franco, JC and Vargas-Castro, AS and Lira-Luna, J and Camacho-Morán, EA and Juarez-Vega, G and Meza-Sánchez, D and Núñez-Álvarez, C and Rull-Gabayet, M and Gómez-Martín, D}, title = {Novel Clinical, Immunological, and Metabolic Features Associated with Persistent Post-Acute COVID-19 Syndrome.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273608}, issn = {1422-0067}, support = {IRE-2152-17-23-1//Fondo de Apoyo a Proyectos de Investigación en el Campo de la Salud/ ; }, mesh = {Humans ; Female ; *COVID-19/immunology/metabolism/complications ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; *SARS-CoV-2 ; Risk Factors ; Biomarkers ; Metabolomics/methods ; Aged ; Metabolome ; Interleukin-8/metabolism ; }, abstract = {The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.}, } @article {pmid39271927, year = {2024}, author = {Radin, JM and Vogel, JM and Delgado, F and Coughlin, E and Gadaleta, M and Pandit, JA and Steinhubl, SR}, title = {Long-term changes in wearable sensor data in people with and without Long Covid.}, journal = {NPJ digital medicine}, volume = {7}, number = {1}, pages = {246}, pmid = {39271927}, issn = {2398-6352}, support = {UL1TR002550//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; }, abstract = {To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions.Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020 .}, } @article {pmid39271699, year = {2024}, author = {Veras Florentino, PT and Araújo, VO and Zatti, H and Luis, CV and Cavalcanti, CRS and de Oliveira, MHC and Leão, AHFF and Bertoldo Junior, J and Barbosa, GGC and Ravera, E and Cebukin, A and David, RB and de Melo, DBV and Machado, TM and Bellei, NCJ and Boaventura, V and Barral-Netto, M and Smaili, SS}, title = {Text mining method to unravel long COVID's clinical condition in hospitalized patients.}, journal = {Cell death & disease}, volume = {15}, number = {9}, pages = {671}, pmid = {39271699}, issn = {2041-4889}, mesh = {Humans ; *Data Mining/methods ; *COVID-19/epidemiology/virology ; Electronic Health Records ; Hospitalization ; SARS-CoV-2/isolation & purification ; Brazil/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is characterized by persistent that extends symptoms beyond established timeframes. Its varied presentation across different populations and healthcare systems poses significant challenges in understanding its clinical manifestations and implications. In this study, we present a novel application of text mining technique to automatically extract unstructured data from a long COVID survey conducted at a prominent university hospital in São Paulo, Brazil. Our phonetic text clustering (PTC) method enables the exploration of unstructured Electronic Healthcare Records (EHR) data to unify different written forms of similar terms into a single phonemic representation. We used n-gram text analysis to detect compound words and negated terms in Portuguese-BR, focusing on medical conditions and symptoms related to long COVID. By leveraging text mining, we aim to contribute to a deeper understanding of this chronic condition and its implications for healthcare systems globally. The model developed in this study has the potential for scalability and applicability in other healthcare settings, thereby supporting broader research efforts and informing clinical decision-making for long COVID patients.}, } @article {pmid39271627, year = {2024}, author = {Xu, WT and An, XB and Chen, MJ and Ma, J and Wang, XQ and Yang, JN and Wang, Q and Wang, DY and Wu, Y and Zeng, L and Qu, Y and Zhao, B and Ai, J}, title = {A Gene Cluster of Mitochondrial Complexes Contributes to the Cognitive Decline of COVID-19 Infection.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39271627}, issn = {1559-1182}, support = {2022ZD0211804//National Science and Technology Innovation 2030/ ; 81870849//National Natural Science/ ; GA21C009//the Key Research and Development Program of Heilongjiang Province/ ; }, abstract = {"Brain fog," a persistent cognitive impairment syndrome, stands out as a significant neurological aftermath of coronavirus disease 2019 (COVID-19). Yet, the underlying mechanisms by which COVID-19 induces cognitive deficits remain elusive. In our study, we observed an upregulation in the expression of genes linked to the inflammatory response and oxidative stress, whereas genes associated with cognitive function were downregulated in the brains of patients infected with COVID-19. Through single-nucleus RNA sequencing (snRNA-seq) analysis, we found that COVID-19 infection triggers the immune responses in microglia and astrocytes and exacerbates oxidative stress in oligodendrocytes, oligodendrocyte progenitors (OPCs), and neurons. Further investigations revealed that COVID-19 infection elevates LUC7L2 expression, which inhibits mitochondrial oxidative phosphorylation (OXPHOS) and suppresses the expression of mitochondrial complex genes such as MT-ND1, MT-ND2, MT-ND3, MT-ND4L, MT-CYB, MT-CO3, and MT-ATP6. A holistic approach to protect mitochondrial complex function, rather than targeting a single molecular, should be an effective therapeutic strategy to prevent and treat the long-term consequences of "long COVID."}, } @article {pmid39270616, year = {2024}, author = {Burch, E and Khan, SA and Stone, J and Asgharzadeh, A and Dawe, J and Ward, Z and Brooks-Pollock, E and Christensen, H}, title = {Early mathematical models of COVID-19 vaccination in high-income countries: a systematic review.}, journal = {Public health}, volume = {236}, number = {}, pages = {207-215}, doi = {10.1016/j.puhe.2024.07.029}, pmid = {39270616}, issn = {1476-5616}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; *COVID-19 Vaccines/administration & dosage ; *Developed Countries ; *Models, Theoretical ; SARS-CoV-2 ; Vaccination/statistics & numerical data ; }, abstract = {OBJECTIVES: Since COVID-19 first emerged in 2019, mathematical models have been developed to predict transmission and provide insight into disease control strategies. A key research need now is for models to inform long-term vaccination policy. We aimed to review the early modelling methods utilised during the pandemic period (2019-2023) in order to identify gaps in the literature and highlight areas for future model development.

STUDY DESIGN: This study was a systematic review.

METHODS: We searched PubMed, Embase and Scopus from 1 January 2019 to 6 February 2023 for peer-reviewed, English-language articles describing age-structured, dynamic, mathematical models of COVID-19 transmission and vaccination in high-income countries that include waning immunity or reinfection. We extracted details of the structure, features and approach of each model and combined them in a narrative synthesis.

RESULTS: Of the 1109 articles screened, 47 were included. Most studies used deterministic, compartmental models set in Europe or North America that simulated a time horizon of 3.5 years or less. Common outcomes included cases, hospital utilisation and deaths. Only nine models included long COVID, costs, life years or quality of life-related measures. Two studies explored the potential impact of new variants beyond Omicron.

CONCLUSIONS: This review demonstrates a need for long-term models that focus on outcome measures such as quality-adjusted life years, the population-level effects of long COVID and the cost effectiveness of future policies - all of which are essential considerations in the planning of long-term vaccination strategies.}, } @article {pmid39269503, year = {2024}, author = {Pisanic, N and Antar, AAR and Hetrich, MK and Demko, ZO and Zhang, X and Spicer, K and Kruczynski, KL and Detrick, B and Clarke, W and Knoll, MD and Thomas, DL and Dawood, FS and Veguilla, V and Karron, RA and Manabe, YC and Heaney, CD}, title = {Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiae447}, pmid = {39269503}, issn = {1537-6613}, abstract = {BACKGROUND: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration.

METHODS: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022.

RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001).

CONCLUSION: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.}, } @article {pmid39268246, year = {2024}, author = {Umakanthan, S and Katwaroo, AR and Bukelo, M and Bg, S and Boralingaiah, P and Ranade, AV and Rangan, P and Shashidhar, S and Kini, JR and Kini, G}, title = {Post-Acute Sequelae of Covid-19: A System-wise Approach on the Effects of Long-Covid-19.}, journal = {American journal of medicine open}, volume = {12}, number = {}, pages = {100071}, pmid = {39268246}, issn = {2667-0364}, abstract = {The SARS-CoV-2 virus responsible for the COVID-19 pandemic has profoundly impacted global health, economics, and society. This review seeks to encompass an overview of current knowledge on COVID-19, including its transmission, pathogenesis, and clinical presentation related to various systems within the human body. COVID-19 is a highly contagious illness that has rapidly spread worldwide. As of August 4, 2023, the WHO reported over 570 million confirmed cases of COVID-19 and over 6.3 million deaths. Although the virus is most common in adults, children can also be infected. Respiratory droplets that are produced when an infected person coughs or sneezes are the primary transmission mode for COVID-19. Additionally, the virus can be disseminated via contact with contaminated surfaces or objects, as it can remain viable for several hours or days. SARS-CoV-2 is a respiratory virus that enters cells by bonding with the angiotensin-converting enzyme 2 (ACE2) receptor. Once inside the cell, the virus replicates and produces new particles that can infect other cells. Interestingly, the effects of post-acute sequelae of SARS-CoV-2 infection (PASC) encompass more than just respiratory system. The findings presented in the data suggest that PASC significantly impacts multiple organs and their respective physiological processes. In light of these observations, we aim to provide a detailed discussion of the relevant findings in this paper. Through our review, we hope to provide healthcare professionals with a deeper understanding of the effects of PASC on the human body, which could ultimately lead to improved patient outcomes and treatment strategies.}, } @article {pmid39267034, year = {2024}, author = {Sprague Martinez, L and Sharma, N and John, J and Battaglia, TA and Linas, BP and Clark, CR and Hudson, LB and Lobb, R and Betz, G and Ojala O'Neill, SO and Lima, A and Doty, R and Rahman, S and Bassett, IV}, title = {Publisher Correction: Long COVID impacts: the voices and views of diverse Black and Latinx residents in Massachusetts.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2483}, doi = {10.1186/s12889-024-19890-z}, pmid = {39267034}, issn = {1471-2458}, } @article {pmid39266971, year = {2024}, author = {Chen, H and Qian, Y and Lu, B and Ma, R and Miao, P and Fu, M and Guo, H and Shen, Y and Shen, Z and Li, Y and Xu, B and Zhang, Y and Xu, J and Chen, B}, title = {Prevalence and factors influencing long COVID among primary healthcare workers after epidemic control policy adjustment in Jiangsu, China.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {964}, pmid = {39266971}, issn = {1471-2334}, support = {No. 2022A02//Jiangsu Provincial Primary Health Development and General Practice Medical Education Research Center/ ; ZKX22019//Health Commission of Nanjing/ ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; China/epidemiology ; Male ; Female ; Adult ; *Health Personnel/statistics & numerical data ; Prevalence ; Middle Aged ; Surveys and Questionnaires ; *SARS-CoV-2 ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: The persistent symptoms arising from COVID-19 infection pose a substantial threat to patients' health, carrying significant implications. Amidst the evolving COVID-19 control strategies in China, healthcare workers (HCWs) endure considerable stress. This study aims to evaluate the prevalence of long COVID infections and their influencing factors among primary HCWs after epidemic control policy adjustment in Jiangsu.

METHODS: A self-designed questionnaire was administered through on-site surveys among primary HCWs in five counties and districts within Jiangsu Province from July 4 to July 20, 2023. Logistic regression analysis was employed to identify factors associated with long COVID.

RESULTS: The prevalence of long COVID among primary HCWs stood at 12.61%, with a 95% confidence interval (CI) of 11.67-13.55%. Among those affected, the most common long COVID symptoms were hypomnesia (4.90%, 95%CI: 4.29-5.51%), sleep difficulties (2.73%, 95%CI: 2.27-3.19%), fatigue (2.35%, 95%CI: 1.92-2.78%), disturbances in the reproductive system (1.93%, 95%CI: 1.54-2.32%), hair loss (1.85%, 95%CI: 1.47-2.23%), and myalgia/arthralgia (1.51%, 95%CI: 1.16-1.86%). Multivariate logistic regression revealed that older age groups (30-45 years (adjusted odds ratio (aOR) = 1.93, 95%CI: 1.44-2.58), 45-60 years (aOR = 2.82, 95%CI: 2.07-3.84)), females (aOR = 1.26, 95%CI: 1.03-1.55), and higher work stress (high stress (aOR = 1.52, 95%CI: 1.24-1.86), extremely high stress (aOR = 1.37, 95%CI: 1.03-1.82)) were more prone to long COVID. Conversely, individuals with educational attainment below the bachelor's degree (aOR = 0.67, 95%CI: 0.55-0.82) and those who received four or more doses of the COVID-19 vaccine (aOR = 0.55, 95%CI: 0.33-0.92) were at a reduced risk.

CONCLUSION: This study investigates the prevalence of long COVID among primary HCWs and identifies key influencing factors. These findings are crucial for assisting in the early identification of COVID-19 patients at risk for long-term complications, developing targeted interventions aimed at optimizing healthcare resource allocation and enhancing the work conditions and quality of life of HCWs. To mitigate the prevalence of long COVID, healthcare providers and local authorities should implement effective measures, such as optimizing work-rest schedules and actively advocating for vaccination.}, } @article {pmid39266315, year = {2024}, author = {Brodén, M and Welfordsson, P and Niemi, M and Diwan, V and Shah, K and Pattanadara, V and Hallgren, M}, title = {Effects of yoga compared with health promotion on health-related quality of life in adults with post-COVID-19 condition: protocol for a randomised controlled trial.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e085525}, pmid = {39266315}, issn = {2044-6055}, mesh = {Humans ; *Yoga ; *Quality of Life ; *COVID-19/psychology/therapy ; Adult ; *Health Promotion/methods ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; Female ; Male ; Fatigue/therapy/etiology ; Exercise ; Post-Acute COVID-19 Syndrome ; Middle Aged ; }, abstract = {INTRODUCTION: Post-COVID-19 condition (post COVID, also known as long COVID) is a global public health issue estimated to affect over 100 million people. Common symptoms include fatigue, dyspnoea and cognitive dysfunction ('brain fog'). Over time, these symptoms have an adverse effect on mental health, physical activity and quality of life (QoL). The condition requires innovative and feasible treatment approaches that can be effective and self-managed. Physical activity is essential for good health; however, aerobic exercise or weightlifting may not be suitable for post COVID patients who experience fatigue or breathlessness. The benefits of yoga include improved flexibility, mobility, body strength and balance. It is also shown to reduce symptoms of fatigue and improve breathing efficiency, mental health and QoL. This study protocol describes the rationale and methods for a randomised controlled trial (RCT) of a yoga-based intervention designed for adults with post COVID.

METHODS AND ANALYSIS: A two-group, parallel, RCT with blinded follow-up assessments. Participants will be randomised with a 1:1 allocation to either a 12-week yoga-based intervention or a 12-week health promotion (active comparison) intervention. In total, 88 participants aged 30-65 years will be recruited and randomised. The primary outcome is health-related QoL (36-item Short-Form). Secondary outcomes are dyspnoea, fatigue, sleep quality, cognitive functions, mental fatigue, depression, anxiety, physical activity, demographic data and physical health measures. Data will be analysed as intention-to-treat basis, using linear mixed modelling. All assessments are conducted at Karolinska Institutet in Stockholm, Sweden. The yoga-based intervention will take place at a yoga studio centrally located in Stockholm city.

ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority, reference number 2023/06518-01. All participants must sign written informed consent before enrolment and are free to withdraw from the study at any point. Key results will be available through research articles and seminars.

TRIAL REGISTRATION NUMBER: German Clinical Trials Register, DRKS00032837.}, } @article {pmid39263197, year = {2024}, author = {Levey, AO and Chen, GH and Ngyuen, A and Ostrosky-Zeichner, L and Hasoon, J and Saroukhani, S and Lin, M}, title = {The Effectiveness and Safety of Stellate Ganglion Block in the Treatment of Symptoms from Long COVID-19: A Pilot Study.}, journal = {Psychopharmacology bulletin}, volume = {54}, number = {4}, pages = {8-17}, pmid = {39263197}, issn = {2472-2448}, mesh = {Humans ; Pilot Projects ; *Stellate Ganglion/drug effects ; Male ; Female ; *Autonomic Nerve Block/methods ; Middle Aged ; *COVID-19 ; Aged ; Treatment Outcome ; Adult ; Post-Acute COVID-19 Syndrome ; Heart Rate/physiology ; }, abstract = {PURPOSE: Pilot study to evaluate the safety and effectiveness of stellate ganglion blocks in the treatment of symptoms related to long COVID infection.

MATERIALS AND METHODS: A total of 17 patients who underwent stellate ganglion block for the treatment of their long COVID symptoms were included. COMPASS-31, GAD-7, PCL-5, and Fatigue Severity Score (FSS) pre and post intervention surveys and data on baseline heartrate and post- block heart rate recorded in the EMR.

RESULTS: A total of 94% of patients reported moderate-to-severe autonomic dysfunction pre-procedure as measured by COMPASS-31. All patients reported some degree of symptomatic improvement from the block. Specifically, patients had significantly lower FSS scores (P = 0.002) and heart rate post-procedure (P = 0.008). Although the decrease in PCL-5 scores after the procedure was clinically meaningful, this change was not statistically significant (P = 0.159). No significant difference was found in pre and post procedure GAD-7 scores (P = 0.101).

CONCLUSIONS: Stellate ganglion block is a safe, low-risk, minimally invasive, and effective procedure in the treatment of symptoms for long COVID. It should be evaluated as an adjunctive treatment of select patients in this population.}, } @article {pmid39262242, year = {2024}, author = {Xu, Y and Zhong, J and Yang, Y and Xie, Y}, title = {Investigation of the potential molecular mechanisms of acupuncture in the treatment of long COVID: a bioinformatics approach.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {8}, pages = {193-200}, doi = {10.14715/cmb/2024.70.8.27}, pmid = {39262242}, issn = {1165-158X}, mesh = {Humans ; *Acupuncture Therapy/methods ; *Computational Biology/methods ; *Protein Interaction Maps/genetics ; *COVID-19/therapy/genetics/virology ; *SARS-CoV-2/genetics ; *Gene Ontology ; Post-Acute COVID-19 Syndrome ; Medicine, Chinese Traditional/methods ; }, abstract = {Long COVID is a poorly understood condition characterized by persistent symptoms following the acute phase of COVID-19, including fatigue, cognitive impairment, and joint pain. Acupuncture, a key component of traditional Chinese medicine treatment, has shown potential in alleviating long COVID symptoms. However, the molecular mechanisms underlying its therapeutic effects remain largely unknown. In this study, we employed bioinformatics approaches to explore the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms. We screened protein targets of active ingredients produced by the body after acupuncture and identified potential therapeutic targets of long COVID. Protein-protein interaction networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify key targets and pathways. Our findings provide valuable insights into the potential molecular mechanisms of acupuncture's therapeutic effects on long COVID symptoms and may contribute to the development of targeted therapies for managing this challenging condition.}, } @article {pmid39261313, year = {2024}, author = {Adorjan, K and Martins-de-Souza, D and Walter, M}, title = {Post-COVID syndrome - novel clinical findings.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1783-1785}, pmid = {39261313}, issn = {1433-8491}, } @article {pmid39259895, year = {2024}, author = {}, title = {What Exactly Is Long Covid?: ITT Episode 37.}, journal = {The New England journal of medicine}, volume = {391}, number = {10}, pages = {e17}, doi = {10.1056/NEJMp2407614}, pmid = {39259895}, issn = {1533-4406}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/complications/diagnosis/economics/psychology ; Disability Evaluation ; Sick Leave/legislation & jurisprudence ; }, } @article {pmid39259107, year = {2024}, author = {Koo, BJ and Choi, HC and Choi, HY and Shin, HS and Won, JH and Hong, SJ and Yang, WJ and Ahn, JK and Park, MJ}, title = {Prolonged loss of intercostal muscle mass and its predictors in COVID-19 patients: A retrospective study from tertiary hospital.}, journal = {Medicine}, volume = {103}, number = {22}, pages = {e38284}, pmid = {39259107}, issn = {1536-5964}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Intercostal Muscles/diagnostic imaging ; *Sarcopenia/diagnostic imaging/epidemiology/etiology ; *Tomography, X-Ray Computed ; Aged ; *Tertiary Care Centers ; SARS-CoV-2 ; Adult ; }, abstract = {Sarcopenia is a contributing factor in the development of long-COVID syndrome. We aimed to investigate how intercostal muscle mass changes over 3 months compared to other chest wall muscles following COVID-19 infection, along with identifying factors contributing to intercostal muscle loss during follow-up. We retrospectively studied 110 COVID-19 patients, analyzing muscle masses in the intercostal, pectoralis, and thoracic 12th vertebra level (T12) on initial and follow-up CT scans. Muscle mass was quantitatively assessed using density histogram analysis. We calculated the muscle difference ratio (MDR) as the following formula: (initial muscle mass - follow-up muscle mass)/initial muscle mass. Patients were categorized into 2 groups: <3 months follow-up (n = 53) and ≥ 3 months follow-up (n = 57). We employed stepwise logistic regression, using intercostal MDR ≥ 25% in follow-up as an independent variable and age < 65 years, ventilator use, steroid use, follow-up > 3 months, hospital stay > 13 days, body mass index < 18.5 kg/m[2], and female gender as dependent variables. The loss of intercostal muscle was the most severe among the 3 chest wall muscles in the CT follow-up. Intercostal MDR was significantly higher in the ≥ 3 months follow-up group compared to the < 3 months group (32.5 ± 23.6% vs 19.0 ± 21.1%, P = .002). There were no significant differences in pectoralis MDR or T12 MDR between the 2 groups. Stepwise logistic regression identified steroid use (3.494 (1.419-8.604), P = .007) and a follow-up period > 3 months [3.006 (1.339-6.748), P = .008] as predictors of intercostal MDR ≥ 25%. The intercostal muscle wasting was profound compared to that in the pectoralis and T12 skeletal muscles in a follow-up CT scan, and the intercostal muscle wasting was further aggravated after 3 months of COVID-19 infection. The use of steroids and a follow-up period exceeding 3 months were significant predictors for ≥ 25% of intercostal muscle wasting in follow-up.}, } @article {pmid39258503, year = {2024}, author = {Rasmussen, IE and Løk, M and Durrer, CG and Lytzen, AA and Foged, F and Schelde, VG and Budde, JB and Rasmussen, RS and Høvighoff, EF and Rasmussen, V and Lyngbæk, M and Jønck, S and Krogh-Madsen, R and Lindegaard, B and Jørgensen, PG and Køber, L and Vejlstrup, N and Pedersen, BK and Ried-Larsen, M and Lund, MAV and Berg, RMG and Christensen, RH}, title = {Impact of a 12-week high-intensity interval training intervention on cardiac structure and function after COVID-19 at 12-month follow-up.}, journal = {Experimental physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/EP092099}, pmid = {39258503}, issn = {1469-445X}, support = {101390//TrygFonden (Tryg Foundation)/ ; 20045//TrygFonden (Tryg Foundation)/ ; N/A//Rigshospitalet/ ; MFE-176582//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; }, abstract = {In patients previously hospitalised for COVID-19, a 12-week high-intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12-month follow-up. In this investigator-blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID-19. At inclusion and at 12-month follow-up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (DLCOc, secondary outcome) was examined by the single-breath method. Symptom severity and functional status were examined by the Post-COVID-19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12-month follow-up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between-group difference of 9.68 [95% CI: 1.72, 17.64] g (P = 0.0182). There was no differences in change from baseline to 12-month follow-up between groups in DLCOc % predicted (-2.45 [-11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID-19, a 12-week supervised HIIT scheme resulted in a preserved LVM at 12-month follow-up but did not affect pulmonary diffusing capacity or symptom severity.}, } @article {pmid39258051, year = {2024}, author = {Mukkawar, RV and Reddy, H and Rathod, N and Kumar, S and Acharya, S}, title = {The Long-Term Cardiovascular Impact of COVID-19: Pathophysiology, Clinical Manifestations, and Management.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66554}, pmid = {39258051}, issn = {2168-8184}, abstract = {The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has resulted in a substantial global health crisis, with effects extending far beyond the acute phase of infection. This review aims to provide a comprehensive overview of the long-term cardiovascular impact of COVID-19, focusing on the pathophysiology, clinical manifestations, diagnostic approaches, management strategies, and future research directions. SARS-CoV-2 induces cardiovascular complications through mechanisms such as inflammation, endothelial dysfunction, and direct myocardial injury, leading to conditions like myocarditis, heart failure, arrhythmias, and thromboembolic events. These long-term effects, collectively called "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC), present significant challenges for healthcare systems and patient management. Diagnostic approaches include imaging techniques and laboratory tests to identify and monitor cardiovascular complications. Management strategies emphasize a holistic approach, incorporating pharmacological treatments and lifestyle modifications. Special attention is required for vulnerable populations, including those with pre-existing cardiovascular conditions. Ongoing research is essential to understand the full spectrum of long-term cardiovascular impacts and to develop effective treatments. This review highlights the critical need for continued vigilance, multidisciplinary care, and research to address the cardiovascular sequelae of COVID-19 and improve long-term health outcomes for survivors.}, } @article {pmid39257875, year = {2024}, author = {Fischer, A and Aguayo, G and Pinker, I and Oustric, P and Lachaise, T and Wilmes, P and Larché, J and Benoy, C and Fagherazzi, G}, title = {Co-design of a voice-based app to monitor long COVID symptoms with its end-users: A mixed-method study.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241272671}, pmid = {39257875}, issn = {2055-2076}, abstract = {BACKGROUND: People living with Long COVID (PWLC), which is still a poorly understood disease, often face major issues accessing proper care and frequently feel abandoned by the healthcare system. PWLC frequently report impaired quality of life because of the medical burden, the variability and intensity of symptoms, and insecurity toward the future. These particular needs justify the development of innovative, minimally disruptive solutions to facilitate the monitoring of this complex and fluctuating disease. Voice-based interactions and vocal biomarkers are promising digital approaches for such health monitoring.

METHODS: Based on a mixed-method approach, this study describes the entire co-design process of Long COVID Companion, a voice-based digital health app to monitor Long COVID symptoms. Potential end-users of the app, both PWLC and healthcare professionals (HCP) were involved to (1) understand the unmet needs and expectations related to Long COVID care and management, (2) to assess the barriers and facilitators regarding a health monitoring app, (3) to define the app characteristics, including future potential use of vocal biomarkers and (4) to develop a first version of the app.

RESULTS: This study revealed high needs and expectations regarding a digital health app to monitor Long COVID symptoms and the readiness to use vocal biomarkers from end-users. The main expectations included improved care and daily life, and major concerns were linked to accessibility and data privacy. Long COVID Companion was developed as a web application and is composed of a health monitoring component that allows auto-evaluation of symptoms, global health, and scoring relevant symptoms and quality of life using standardized questionnaires.

CONCLUSIONS: The Long COVID Companion app will address a major gap and provide day-to-day support for PWLC. However, further studies will be needed following its release, to evaluate its acceptability, usability and effectiveness.}, } @article {pmid39257640, year = {2024}, author = {Kandel, D and Knulst, AJ and Riggsbee, J and Riggsbee, SO and Tamang, S and Bhattarai, HB and Karn, M}, title = {Use of Locally Produced Novel Low-Cost 3D Printed Respiratory Muscle Strength Trainer Device (RMSTD) for Long COVID-Rehabilitation: An Innovative Case Report.}, journal = {Case reports in medicine}, volume = {2024}, number = {}, pages = {8877421}, pmid = {39257640}, issn = {1687-9627}, abstract = {Introduction. This article details the development and use of a low-cost, custom RMST device for a patient with long COVID who had received positive airway flow support during ICU treatment. By sharing our successful management of respiratory muscle weakness in a severe COVID-19 patient, we aim to contribute to the broader conversation around effective long COVID management. Case Description. A patient with respiratory muscle weakness used a hospital-made RMST device. The training involved ten short forced exhalations per cycle for five cycles, followed by five long forced exhalations held for five seconds. Additionally, the patient learned lower abdominal and box breathing techniques. The patient showed significant improvement, using the RMST device without supplemental oxygen within 24 hours and completely weaned off by day 5. By discharge, the patient could complete the RMST exercise regime and achieved 290 meters in the 6MWT. After six weeks of outpatient therapy, the patient used the RMST device at 80 cm H2O and increased their 6MWT distance to 390 meters. Device Description. The RMST device was designed for in-house production with a 3D-printed PETG cap, base, and plunger, and a standard pen spring. Its design mimicked a standard PEEP valve with a different geometry. The spring closed the valve until a pressure threshold was reached, allowing airflow. The adjustable pressure threshold ranged from -40 to +40 cm H2O, calibrated in 10 cm H2O increments by measuring displaced water column height. Discussion and Limitation. COVID-19 can cause long-term respiratory issues needing proper management and rehabilitation. Inspiratory muscle training benefits those recovering from severe COVID-19 who were weaned from mechanical ventilation. However, the device's design and production method are unsuitable for large-scale and commercial production. Rehabilitation centers should prepare for postintensive care syndrome in post-COVID-19 individuals, with interprofessional teams addressing various recovery aspects. Early medical attention and therapy can improve patients' quality of life.}, } @article {pmid39257263, year = {2024}, author = {Hristova, M and Massaldjieva, R and Chervenkov, L and Atanassova, P}, title = {Cognitive functions in a 29-year-old male with post-COVID syndrome and long-term psoriasis - a case study.}, journal = {Folia medica}, volume = {66}, number = {4}, pages = {587-591}, doi = {10.3897/folmed.66.e124311}, pmid = {39257263}, issn = {1314-2143}, mesh = {Humans ; Male ; *Psoriasis/complications/psychology ; *COVID-19/complications/psychology ; *Post-Acute COVID-19 Syndrome ; Adult ; Cognition ; }, abstract = {Post-acute COVID syndrome (PACS), or long COVID, is a newly defined condition emerging as a widespread post-pandemic diagnosis with prevalent neuro-psychiatric symptoms and possible neuroinflammation-associated pathogenetic mechanisms.}, } @article {pmid39255548, year = {2024}, author = {Cázares-Lara, JO and Ordinola-Navarro, A and Carmona-Aguilera, Z and Benitez-Altamirano, GM and Beltran-Ontiveros, LD and Ramirez-Hinojosa, JP and Lopez-Vejar, C and Lopez-Luis, BA}, title = {Main Predictors of Decreasing in Quality of Life in Patients With Post-COVID-19: A Cross-Sectional Study.}, journal = {Value in health regional issues}, volume = {45}, number = {}, pages = {101039}, doi = {10.1016/j.vhri.2024.101039}, pmid = {39255548}, issn = {2212-1102}, abstract = {OBJECTIVE: We aimed to assess physical and psychosomatic manifestations of patients with long COVID and their association with a decreased patient's quality of life (QOL) or different times elapsed since the COVID-19 diagnosis.

METHODS: This is a cross-sectional study. We retrospectively collected the clinical characteristics of adult patients who had tested positive for SARS-CoV-2 and had symptoms at least as early as 4 weeks after COVID-19 in México City between April 2020 and February 2021. A total of 179 were included. They answered questions to define chronic symptoms. The Sniffin' Sticks Screening 12 test olfactory evaluation was performed. The diminish of QOL was defined by ≥10 points in the EuroQol visual analog scale between pre- and post-COVID-19, and each dimension of EQ-5D-5L test was evaluated. Chi-square test, Fisher's exact test, Student t test, Wilcoxon rank-sum, and signed-rank test were used as required. A backward stepwise logistic regression analysis determined the factors associated with a decrease in QOL. All analyses were performed using R software version 3.6.3 (R Foundation).

RESULTS: In the multivariable analysis, post-COVID-19 pain/discomfort (adjusted odds ratio [aOR] 2.5 [1.66-9.68]; P = .01), anxiety/depression (aOR 13 [1.44-17.23]; P = .03), and persistence of ≥3 symptoms (aOR 2.6 [0.96-7.47]; P = .05) remained statistically significant associated with decreased QOL.

CONCLUSIONS: Patients with long COVID-19 have decreased QOL mainly associated with pain/discomfort, anxiety/depression, and ≥3 persistent symptoms. Our findings enhanced the notion of a strong psychosomatic factors involved with long COVID-19. Therefore, these patients might benefit from neuropsychological rehabilitation, although the effect of such interventions should be evaluated.}, } @article {pmid39254484, year = {2024}, author = {Pineros-Garcia, LN and Gonzalez-Sanchez, NI and Calvo-Henrique, C and Rojas-Lechuga, MJ and Hopkins, C and Mullol, J and Alobid, I}, title = {SNOT-22 in general population, a Spanish cohort study with an updated meta-analysis.}, journal = {Rhinology}, volume = {62}, number = {6}, pages = {700-709}, doi = {10.4193/Rhin24.233}, pmid = {39254484}, issn = {0300-0729}, mesh = {Humans ; *COVID-19/complications ; *Olfaction Disorders/physiopathology ; Female ; Prospective Studies ; Male ; Middle Aged ; *SARS-CoV-2 ; Spain ; Adult ; Aged ; Smell/physiology ; Cohort Studies ; }, abstract = {BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL.

METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas.

RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥ 5.5 points), compared to 22% of non-adherents. In retronasal olfactory identification, 56% of adherents achieved a clinically significant improvement (≥4 points), compared to 16% of non-adherents.

CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.}, } @article {pmid39253580, year = {2024}, author = {Zhou, J and Wang, Y and Xu, R}, title = {Association of COVID-19 infection and the risk of new incident diabetes: a systematic review and meta-analysis.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1429848}, pmid = {39253580}, issn = {1664-2392}, mesh = {Humans ; *COVID-19/epidemiology ; *Diabetes Mellitus, Type 1/epidemiology ; *Diabetes Mellitus, Type 2/epidemiology ; Incidence ; Risk Factors ; }, abstract = {BACKGROUND: As the world population recovers from the COVID-19 infection, a series of acute sequelae emerge including new incident diabetes. However, the association between COVID-19 infection and new incident diabetes is not fully understood. We purpose to determine the risk of new incident diabetes after COVID-19 infection.

METHODS: PubMed, Embase, and Cochrane Library were used as databases to search for cohort studies published from database inception to February 4, 2024. Two reviewers independently conducted the study screening, data extraction, and risk of bias assessment. A random-effects model was adopted to pool the hazard ratio (HR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted to explore the potential influencing factors.

RESULTS: A total of 20 cohort studies with over 60 million individuals were included. The pooling analysis illustrates the association between COVID-19 infection and an increased risk of new incident diabetes (HR = 1.46; 95% CI: 1.38-1.55). In subgroup analysis, the risk of type 1 diabetes was HR=1.44 (95% CI: 1.13-1.82), and type 2 diabetes was HR=1.47 (95% CI: 1.36-1.59). A slightly higher risk of diabetes was found in males (HR=1.37; 95% CI: 1.30-1.45) than in females (HR=1.29; 95% CI: 1.22-1.365). The risk of incident diabetes is associated with hospitalization: non-hospitalized patients have an HR of 1.16 (95% CI: 1.07-1.26), normal hospitalized patients have an HR of 2.15 (95% CI: 1.33-3.49), and patients receiving intensive care have the highest HR of 2.88 (95% CI: 1.73-4.79).

CONCLUSIONS: COVID-19 infection is associated with an elevated risk of new incident diabetes. Patients ever infected with COVID-19 should be recognized as a high-risk population with diabetes.

https://www.crd.york.ac.uk/prospero, identifier CRD42024522050.}, } @article {pmid39252866, year = {2024}, author = {Evering, TH and Moser, C and Jilg, N and Ritz, J and Wohl, DA and Li, JZ and Margolis, D and Javan, AC and Eron, JJ and Currier, JS and Daar, ES and Smith, DM and Hughes, MD and Chew, KW and , }, title = {Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial.}, journal = {EClinicalMedicine}, volume = {75}, number = {}, pages = {102787}, pmid = {39252866}, issn = {2589-5370}, support = {UM1 AI069423/AI/NIAID NIH HHS/United States ; UM1 AI069424/AI/NIAID NIH HHS/United States ; UM1 AI069419/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; UM1 AI069412/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID.

METHODS: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo.

FINDINGS: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.

INTERPRETATION: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.

FUNDING: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.}, } @article {pmid39252826, year = {2024}, author = {Fumagalli, RM and Voci, D and Bikdeli, B and Bingisser, R and Colucci, G and Forgo, G and Gerardi, T and Gerber, B and Grigorean, A and Klok, FA and Righini, M and Robert-Ebadi, H and Stortecky, S and Ulrich, S and Wolf, S and Wyss, D and Hobohm, L and Kucher, N and Barco, S and , }, title = {Long-term course of ambulatory patients with COVID-19 initially treated with enoxaparin vs no anticoagulation: final analysis of the OVID (enoxaparin for outpatients with COVID-19) randomized trial.}, journal = {Research and practice in thrombosis and haemostasis}, volume = {8}, number = {5}, pages = {102534}, pmid = {39252826}, issn = {2475-0379}, abstract = {BACKGROUND: Early thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown.

OBJECTIVES: To assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients.

METHODS: The OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post-COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale.

RESULTS: Of 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group).

CONCLUSION: Early thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19.}, } @article {pmid39252682, year = {2024}, author = {Ra, SH and Chang, E and Kwon, JS and Kim, JY and Son, J and Kim, W and Jang, CY and Jang, HM and Bae, S and Jung, J and Kim, MJ and Chong, YP and Lee, SO and Choi, SH and Kim, YS and Lee, KH and Kim, SH}, title = {Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).}, journal = {Journal of Korean medical science}, volume = {39}, number = {35}, pages = {e237}, pmid = {39252682}, issn = {1598-6357}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, mesh = {Humans ; *COVID-19/immunology/diagnosis/blood ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology/isolation & purification ; Prospective Studies ; Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Coronavirus Nucleocapsid Proteins/immunology ; Phosphoproteins/blood ; Cytokines/blood ; }, abstract = {BACKGROUND: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC.

METHODS: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis.

RESULTS: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range.

CONCLUSION: Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.}, } @article {pmid39252604, year = {2024}, author = {Yang, X and Shi, F and Zhang, H and Giang, WA and Kaur, A and Chen, H and Li, X}, title = {Long COVID among people with HIV: A systematic review and meta-analysis.}, journal = {HIV medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/hiv.13708}, pmid = {39252604}, issn = {1468-1293}, support = {/NH/NIH HHS/United States ; R21AI170159-01A1//University of South Carolina/ ; }, abstract = {BACKGROUND: People with HIV might be at an increased risk of long COVID (LC) because of their immune dysfunction and chronic inflammation and alterations in immunological responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]). This systematic review aimed to evaluate the association between HIV infection and LC and the prevalence and characteristics of and risk factors for LC among people with HIV.

METHODS: Multiple databases, including Embase, PubMed, PsycINFO, Web of Science, and Sociological Abstracts, were searched to identify articles published before June 2023. Published articles were included if they presented at least one LC outcome measure among people with HIV and used quantitative or mixed-methods study designs. For effects reported in three or more studies, meta-analyses using random-effects models were performed using R software.

RESULTS: We pooled 39 405 people with HIV and COVID-19 in 17 eligible studies out of 6158 publications in all the databases. It was estimated that 52% of people with HIV with SARS-CoV-2 infection developed at least one LC symptom. Results from the random-effects model showed that HIV infection was associated with an increased risk of LC (odds ratio 2.20; 95% confidence interval 1.25-3.86). The most common LC symptoms among people with HIV were cough, fatigue, and asthenia. Risk factors associated with LC among people with HIV included a history of moderate-severe COVID-19 illness, increased interferon-gamma-induced protein 10 or tumour necrosis factor-α, and decreased interferon-β, among others.

CONCLUSIONS: The COVID-19 pandemic continues to exacerbate health inequities among people with HIV because of their higher risk of developing LC. Our review is informative for public health and clinical communities to develop tailored strategies to prevent aggravated LC among people with HIV.}, } @article {pmid39251404, year = {2024}, author = {Theresa, C and Katebe, B and Shibao, CA and Kirabo, A}, title = {Arterial stiffness in adults with Long COVID in sub-Saharan Africa.}, journal = {Physiological reports}, volume = {12}, number = {17}, pages = {e70029}, pmid = {39251404}, issn = {2051-817X}, support = {R01 HL144941/HL/NHLBI NIH HHS/United States ; R01HL144941//National Institutes of Health grants/ ; R01HL147818//National Institutes of Health grants/ ; }, mesh = {Humans ; *Vascular Stiffness/physiology ; Male ; Female ; *COVID-19/physiopathology ; Adult ; *Pulse Wave Analysis ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Africa South of the Sahara/epidemiology ; Young Adult ; Carotid Arteries/physiopathology ; }, abstract = {Severe acute coronavirus-2 (SARS-CoV-2) infection has been associated with endothelial damage, and impaired nitric oxide production, which results in arterial stiffness and increased risk of cardiovascular disease. Long COVID is a term used to describe the persistence or the development of new symptoms that can occur after an acute infection. Little is known about the association between arterial stiffness and Long COVID. An observational, cross-sectional study in which arterial stiffness was measured with pulse wave velocity (PWV) was carried out in 74 participants between 19 and 40 years old (53 with Long COVID, 21 age and gender-matched controls). Data was collected from participants between 1 and 9 months after acute COVID-19 infection using the Complior analyze unit protocol. The Long COVID group had higher carotid-radial-PWV (crPWV) than controls (10 m/s interquartile range [IQR] 8.5-11.2 m/s) versus 8.8 m/s (IQR 7.7-9.2 m/s) as was their carotid-radial-arterial stiffness index (crASI) (2.26 cm/ms (IQR 1.9-2.56 cm/ms) vs. 2.01 cm/ms (IQR 1.82-2.27 cm/ms); p < 0.05) in both. They also had more type-A waveforms, indicating increased arterial stiffening. Peripheral arterial stiffness was higher in adults with Long COVID than in controls who were never infected with SARS-CoV-2 as noted by the elevated levels of crPWV and crASI among adults with Long COVID.}, } @article {pmid39249604, year = {2024}, author = {Garland, E}, title = {New Chaotic Reality: Creative Writing Workshops for Long COVID Patients.}, journal = {The Journal of medical humanities}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10912-024-09891-9}, pmid = {39249604}, issn = {1573-3645}, abstract = {In a widely cited 2017 study, Robinson et al. (2017) found that 'emotionally expressive' writing makes physical wounds heal faster when compared to writing that did not engage the emotions. The Writing Long COVID project at Aberystwyth University engaged similar territory in a recent pilot study. Participants' writing activities explored how literary production can affect a person's experience of this new chronic condition, as well as contribute to our understanding of its symptoms. In this short essay, I show how we designed a course of short-duration online workshops that increased accessibility for people with Long COVID-related fatigue. I also argue that future Long COVID creative activities should let their timing, venue, content, and structure be influenced by the preferences of the Long COVID patient. The preliminary study suggests that the traditional parameters of the writing workshop, including its duration, could deter participation in potentially beneficial creative activities.}, } @article {pmid39248006, year = {2024}, author = {Kohler, H}, title = {Immune Jumping in Autoimmune Long-Covid.}, journal = {Monoclonal antibodies in immunodiagnosis and immunotherapy}, volume = {43}, number = {5}, pages = {131-134}, doi = {10.1089/mab.2024.0006}, pmid = {39248006}, issn = {2167-9436}, mesh = {Humans ; *Autoimmune Diseases/immunology/virology ; *Post-Acute COVID-19 Syndrome/immunology/virology ; *SARS-CoV-2/immunology ; Autoantigens/immunology ; *Antibodies, Viral/immunology ; }, abstract = {This Long-Covid disease, mild or severe, is multiorgan or system-wide, spanning from fatigue to clotting abnormalities and autoantibody. The spectrum of different symptoms in Long-Covid diseases makes it difficult to point to a common immunopathogenic etiology. Different immune pathways are presented and critically evaluated. A hypothesis is advanced that indicates autoimmune reactions as cause for Long-Covid disease. The immune network pathway describes a redirection of the nominal anti-SARS-CoV response towards an autoimmune target. Several therapeutic interventions are suggested to suppress the autoimmune pathway.}, } @article {pmid39247972, year = {2024}, author = {Karachaliou, M and Ranzani, O and Espinosa, A and Iraola-Guzmán, S and Castaño-Vinyals, G and Vidal, M and Jiménez, A and Bañuls, M and Nogués, EA and Aguilar, R and Garcia-Aymerich, J and de Cid, R and Dobaño, C and Moncunill, G and Kogevinas, M}, title = {Antibody responses to common viruses according to COVID-19 severity and postacute sequelae of COVID-19.}, journal = {Journal of medical virology}, volume = {96}, number = {9}, pages = {e29862}, doi = {10.1002/jmv.29862}, pmid = {39247972}, issn = {1096-9071}, support = {//RYC 2020-029886 I/ AEI/10.13039/501100011033/ ; //Fundació Privada Daniel Bravo Andreu/ ; //Generalitat de Catalunya through the Centres de Recerca de Catalunya (CERCA)/ ; //END-VOC Project (Horizon 2021-2024)/ ; //Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 programme (CEX2018-000806-S)/ ; //Acción de Dinamización del ISCIII-MINECO/ ; ADE 10/00026//Ministry of Health of the Generalitat of Catalunya/ ; SGR 01537//Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)/ ; PI18/01512//Spanish National/ ; TED2021-130626B-I00//Spanish National/ ; La MaratoTV3 167/C/2021//Spanish National/ ; 101046314//European Union/ ; //MENARINI/ ; }, mesh = {Humans ; *COVID-19/immunology/virology ; *Antibodies, Viral/blood ; Male ; Female ; Middle Aged ; *Immunoglobulin G/blood ; Adult ; Severity of Illness Index ; Aged ; SARS-CoV-2/immunology ; Immunoglobulin A/blood ; Antibody Formation ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; }, abstract = {Limited research suggests that certain viruses reactivate in severe-acute-respiratory-syndrome-coronavirus 2 infection, contributing to the development of postacute sequelae of COVID-19 (PASC). We examined 1083 infected individuals from a population-based cohort, and assessed differences in plasma immunoglobulin (Ig)G and immunoglobulin A levels against Epstein-Barr virus (EBV), cytomegalovirus, varicella zoster virus (VZV), BK polyomavirus, KI polyomavirus, WU polyomavirus (WUPyV), respiratory syncytial virus, and Adv-36 according to the severity of previous COVID-19 and PASC history. Individuals who had experienced severe COVID-19 had higher antibody responses to latent viruses. Ever PASC, active persistent PASC, and PASC with neuropsychiatric symptoms were associated with higher immnoglobulin G to EBV early antigen-diffuse, VZV, and WUPyV even among individuals without previous severe COVID-19.}, } @article {pmid39245151, year = {2024}, author = {McDonald, E and Pittet, LF and Barry, SE and Bonten, M and Campbell, J and Croda, J and Croda, MG and Dalcolmo, MP and Davidson, A and de Almeida E Val, FF and Dos Santos, G and Gardiner, K and Gell, G and Gwee, A and Krastev, A and Lacerda, MVG and Lucas, M and Lynn, DJ and Manning, L and McPhate, N and Perrett, KP and Post, JJ and Prat-Aymerich, C and Quinn, LE and Richmond, PC and Wood, NJ and Messina, NL and Curtis, N and , }, title = {Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: Insights from prospectively collected data in the BRACE trial.}, journal = {The Journal of infection}, volume = {89}, number = {5}, pages = {106267}, pmid = {39245151}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Respiratory Tract Infections/virology/epidemiology ; Health Personnel/statistics & numerical data ; }, abstract = {BACKGROUND: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospectively collected data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illness, to identify factors associated with the risk of PACS, and to explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.

METHODS: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms.

FINDINGS: Compared to those with a non-COVID-19 illness, participants with COVID-19 had significantly more severe illness (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age 40-59 years (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath).

INTERPRETATION: Healthcare workers with COVID-19 were more likely to have severe and longer-lasting symptoms than those with a non-COVID-19 respiratory illness, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19.}, } @article {pmid39244203, year = {2024}, author = {Lopes-Santos, LE and de Lacerda Ferreira, D and de Angelis, G and Foss, MP and Trevisan, AC and de Lacerda, KJCC and Tumas, V and Bellissimo-Rodrigues, F and Wichert-Ana, L}, title = {How Mild Is the Mild Long COVID? A Comprehensive Neuropsychological Assessment of Patients with Cognitive Complaints.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {}, number = {}, pages = {}, doi = {10.1093/arclin/acae071}, pmid = {39244203}, issn = {1873-5843}, support = {2021/12671-3//São Paulo Research Foundation/ ; }, abstract = {The global impact of the Coronavirus Disease (COVID-19) pandemic has extended beyond physical health, leading to widespread mental health issues. Beyond respiratory symptoms, there is a growing concern about long-term cognitive effects, particularly in individuals who experienced mild cases of the infection. We aimed to investigate the neuropsychological aspects of long-term COVID-19 in non-hospitalized adults compared with a control group. This cross-sectional study included 42 participants, 22 individuals with a history of mild COVID, and 20 healthy controls. The participants were recruited from the community and underwent a comprehensive neuropsychological assessment. Participants from the mild COVID group reported cognitive symptoms persisting for an average of 203.86 days and presented a higher frequency of psychological treatment history (81.8%) compared with the control group (25.0%). History of anxiety disorders was more prevalent in the mild COVID group (63.6%) than in the control group (20.0%). Significant reductions in verbal working memory were observed in the mild COVID group. Levels of anxiety were found to have a significant impact on difficulties with visual recognition memory. This study reveals important neuropsychological alterations in individuals following mild COVID-19, emphasizing executive functions deficits. Our findings underscore the persistence of these deficits even in non-hospitalized cases, suggesting potential inflammatory mechanisms in the central nervous system. The study highlights the need for comprehensive assessments and targeted interventions to address the diverse cognitive impacts on individuals recovering from COVID-19.}, } @article {pmid39243076, year = {2024}, author = {Brus, IM and Spronk, I and Polinder, S and Loohuis, AGMO and Tieleman, P and Heemskerk, SCM and Biere-Rafi, S and Haagsma, JA}, title = {Self-perceived barriers to healthcare access for patients with post COVID-19 condition.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {1035}, pmid = {39243076}, issn = {1472-6963}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Health Services Accessibility ; Middle Aged ; Adult ; Netherlands ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Patient Acceptance of Health Care/statistics & numerical data/psychology ; Young Adult ; }, abstract = {BACKGROUND: Many patients with post COVID-19 condition (PCC) require healthcare services. However, qualitative studies indicate that patients with PCC encounter many barriers to healthcare access. This cross-sectional study aimed to determine how many PCC patients report barriers to healthcare access and which barriers are reported, and to explore differences between subgroups.

METHODS: Data were collected via an online survey from 10,462 adult patients with a confirmed or suspected COVID-19 infection in the Netherlands, who experienced persisting symptoms ≥ 3 months after the initial infection. To study self-perceived barriers, a list of eleven possible barriers was used, covering multiple aspects of healthcare access. Differences between subgroups based on sociodemographic characteristics, medical characteristics, PCC symptoms (fatigue, dyspnoea, cognitive problems, anxiety and depression), and healthcare use (general practitioner, paramedical professional, medical specialist, occupational physician and mental health professional) were studied through multivariable multinomial (0 vs. 1 vs. > 1 barrier) and binomial regression analyses (for each individual barrier).

RESULTS: A total of 83.2% of respondents reported at least one barrier to healthcare access. Respondents reported a median of 2.0 (IQR = 3.0) barriers. The barriers "I didn't know who to turn to for help" (50.9%) and "No one with the right knowledge/skills was available" (36.8%) were most frequently reported. Respondents with younger age, higher educational level, not hospitalized during acute COVID-19 infection, longer disease duration, who had more severe PCC symptoms, and who did not consult an occupational physician or paramedical professional, were more likely to report barriers. Analyses per barrier showed that women were more likely to report financial and help-seeking barriers, while men were more likely to report barriers related to availability of care. Hospitalized respondents were less likely to report barriers related to availability of care, but not less likely to report financial or help-seeking barriers.

CONCLUSIONS: This study shows that the majority of patients with PCC experiences barriers to healthcare access. Particular attention should be paid to younger, non-hospitalized patients with a long disease duration and severe PCC symptoms. Efforts to remove barriers should focus not only on improving availability of care, but also on helping patients navigate care pathways.}, } @article {pmid39242614, year = {2024}, author = {Lee, YR and Liou, CW and Liu, IH and Chang, JM}, title = {A nonadjuvanted HLA-restricted peptide vaccine induced both T and B cell immunity against SARS-CoV-2 spike protein.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20579}, pmid = {39242614}, issn = {2045-2322}, mesh = {*Spike Glycoprotein, Coronavirus/immunology ; Animals ; Humans ; Mice ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; *Vaccines, Subunit/immunology/administration & dosage ; *B-Lymphocytes/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; *COVID-19/immunology/prevention & control ; Female ; HLA Antigens/immunology ; Mice, Inbred BALB C ; Protein Subunit Vaccines ; }, abstract = {During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2. The specific lysis activity assay of T cells was performed for direct activation of cytotoxic T lymphocytes by UC peptides. Mice were immunized for immunogenicity of UC peptides in vivo and immunized sera was assay for complement cytotoxicity assay. Results appeared that through the engagement of UC peptides and immune molecules, HLA-I and II, that CTLs elicited cytotoxic activity by recognizing SARS-CoV-2 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides also showed immunogenicity and generated a specific antibody in mice by both intramuscular injection and oral delivery without adjuvant formulation. In conclusion, a T-cell vaccine could provide long-lasting protection against SARS-CoV-2 either during reinfection or during SARS-CoV-2 rebound. Due to its ability to eradicate SARS-CoV-2 virus-infected cells, a COVID-19 T-cell vaccine might provide a solution to lower COVID-19 severity and long COVID-19.}, } @article {pmid39241905, year = {2024}, author = {Tudoran, C and Tudoran, M and Abu-Awwad, A and Abu-Awwad, SA and Faur, C and Crisan-Vida, M and Stoicu-Tivadar, L and Voiţă-Mekereş, F}, title = {Sex-related differences concerning the profile and evolution of cardiovascular complications in patients with post-acute COVID-19 syndrome.}, journal = {Life sciences}, volume = {356}, number = {}, pages = {123044}, doi = {10.1016/j.lfs.2024.123044}, pmid = {39241905}, issn = {1879-0631}, mesh = {Humans ; Male ; Female ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; Middle Aged ; Adult ; *Echocardiography ; Sex Factors ; SARS-CoV-2 ; Cardiovascular Diseases/etiology ; Ventricular Dysfunction, Left/physiopathology ; Sex Characteristics ; Ventricular Dysfunction, Right/physiopathology/diagnostic imaging ; Ventricular Function, Left ; }, abstract = {BACKGROUND: During the COVID-19 pandemic sex-related differences concerning the spectrum of cardiovascular complications have been observed in the acute infection, and during recovery. This study aims to emphasize sex-related disparities regarding left ventricular systolic function (LVSF), right ventricular function (RVF), diastolic dysfunction (DD), and pericardial pathologies during the post-COVID-19 syndrome.

METHODS: 274 patients with post-acute COVID-19 syndrome, 127 men and 147 women, aged under 55, were evaluated within 90 days after the acute illness and followed at 3 and 6 months.

RESULTS: Based on detailed transthoracic echocardiography (TTE), we identified significantly more frequently (p˂0.001) altered LVSF in men, while in women impaired RVF, and DD were significantly more common (p˂0.001). Pericardial impairment did not seem to be influenced by gender. The TTE parameters characterizing these patterns were correlated with the severity of the initial infection and the time elapsed since and alleviated in time. The multivariate regression analysis confirmed these sex-related associations and their impact on patients' functional status.

CONCLUSIONS: Male patients had a higher tendency to develop altered LVSF, while female subjects had more frequently impaired RVF and DD. These abnormalities alleviated in time and exerted a significant influence on patients' functional status.}, } @article {pmid39240571, year = {2024}, author = {Anderer, S}, title = {NIH: Routine Lab Tests Not a Reliable Way to Diagnose Long COVID.}, journal = {JAMA}, volume = {332}, number = {13}, pages = {1043-1044}, doi = {10.1001/jama.2024.17608}, pmid = {39240571}, issn = {1538-3598}, } @article {pmid39240544, year = {2024}, author = {Rubin, R}, title = {The Latest Research About Paxlovid: Effectiveness, Access, and Possible Long COVID Benefits.}, journal = {JAMA}, volume = {332}, number = {13}, pages = {1040-1042}, doi = {10.1001/jama.2024.16432}, pmid = {39240544}, issn = {1538-3598}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology/prevention & control ; *COVID-19 Drug Treatment/methods/statistics & numerical data ; Drug Combinations ; *Antiviral Agents/therapeutic use ; Lactams/therapeutic use ; Leucine/therapeutic use ; Nitriles/therapeutic use ; Proline/therapeutic use ; Ritonavir/therapeutic use ; Severity of Illness Index ; Health Inequities ; *Post-Acute COVID-19 Syndrome/drug therapy/epidemiology/prevention & control ; Drug Prescriptions/statistics & numerical data ; }, } @article {pmid39240511, year = {2024}, author = {di Filippo, L and Franzese, V and Santoro, S and Doga, M and Giustina, A}, title = {Long COVID and pituitary dysfunctions: a bidirectional relationship?.}, journal = {Pituitary}, volume = {27}, number = {6}, pages = {955-969}, pmid = {39240511}, issn = {1573-7403}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *SARS-CoV-2 ; *Hypothalamo-Hypophyseal System/physiopathology/metabolism ; Post-Acute COVID-19 Syndrome ; Pituitary-Adrenal System/physiopathology/metabolism ; Hypogonadism/physiopathology/epidemiology ; Pituitary Diseases/physiopathology/epidemiology/complications ; Adrenal Insufficiency/physiopathology/epidemiology ; Hypothyroidism/physiopathology/epidemiology/complications ; Pituitary Gland/physiopathology/metabolism ; }, abstract = {Long COVID is a novel emerging syndrome known to affect multiple health areas in patients previously infected by SARS-CoV-2 markedly impairing their quality of life. The pathophysiology of Long COVID is still largely poorly understood and multiple mechanisms were proposed to underlie its occurrence, including alterations in the hormonal hypothalamic-pituitary axes. Aim of this review is to present and discuss the potential negative implications of these hormonal dysfunctions in promoting and influencing the Long COVID syndrome. To date, the hypothalamic-pituitary-adrenal axis is the mostly investigated and several studies have reported a prolonged impairment leading to mild and subclinical forms of central adrenal insufficiency. Few data are also available regarding central hypogonadism, central hypothyroidism and growth hormone (GH) deficiency. A high prevalence of central hypogonadism in COVID-19 survivors several months after recovery was consistently reported in different cohorts. Conversely, very few data are available on the hypothalamic-pituitary-thyroid axis function that was mainly shown to be preserved in COVID-19 survivors. Finally, a potential impairment of the hypothalamic-GH axis in Long COVID has also been reported. These data altogether may suggest a novel possible pituitary-centred pathophysiological view of Long COVID syndrome which if confirmed by large clinical studies may have relevant implication for the diagnostic and therapeutic approach at least in a subset of patients with the syndrome.}, } @article {pmid39240417, year = {2024}, author = {Haunhorst, S and Dudziak, D and Scheibenbogen, C and Seifert, M and Sotzny, F and Finke, C and Behrends, U and Aden, K and Schreiber, S and Brockmann, D and Burggraf, P and Bloch, W and Ellert, C and Ramoji, A and Popp, J and Reuken, P and Walter, M and Stallmach, A and Puta, C}, title = {Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Infection}, volume = {}, number = {}, pages = {}, pmid = {39240417}, issn = {1439-0973}, abstract = {BACKGROUND: A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated.

PURPOSE AND METHODS: In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM.

RESULTS: Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.}, } @article {pmid39238844, year = {2024}, author = {}, title = {Correction to: Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae509}, doi = {10.1093/ofid/ofae509}, pmid = {39238844}, issn = {2328-8957}, abstract = {[This corrects the article DOI: 10.1093/ofid/ofae462.].}, } @article {pmid39238359, year = {2024}, author = {Deng, J and Qin, C and Lee, M and Lee, Y and You, M and Liu, J}, title = {Effects of rehabilitation interventions for old adults with long COVID: A systematic review and meta-analysis of randomised controlled trials.}, journal = {Journal of global health}, volume = {14}, number = {}, pages = {05025}, pmid = {39238359}, issn = {2047-2986}, mesh = {Aged ; Humans ; Middle Aged ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome/diagnosis/psychology/rehabilitation ; }, abstract = {BACKGROUND: There is limited evidence on the effectiveness of the existing rehabilitation interventions for old adults with long coronavirus disease (COVID), which is of particular concern among old adults.

METHODS: We systematically searched studies published in PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases from their inception to 15 November 2023. Randomised controlled trials (RCTs) compared rehabilitation interventions with other controls in old adults (mean/median age of 60 or older) with long COVID were included. We performed a meta-analysis to compare the effects of the rehabilitation interventions with the common control group. Mean difference (MD) or standardised mean difference (SMD) with its 95% confidence intervals (CI) were used as summary statistics. Moreover, subgroup analyses based on the intervention programmes, the severity of acute infection, and the age of participants were carried out.

RESULTS: A total of 11 RCTs involving 832 participants (64.37 ± 7.94 years, 52.2% were men) were included in the analysis. Compared with the control groups, rehabilitation interventions significantly improved 6-minute walking test (6 MWT; MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand test (MD = 4.11 number of stands (n), 95% CI = 2.46, 5.76, P < 0.001), all aspects of quality of life, independence in activities of daily living (SMD = 0.31, 95% CI = 0.14, 0.48, P < 0.001), and relieved fatigue (SMD = -0.66, 95% CI = -1.13, -0.19, P < 0.01), depression (SMD = -0.89, 95% CI = -1.76, -0.02, P < 0.05) and anxiety (SMD = -0.81, 95% CI = -1.58, -0.05, P < 0.05). However, the improvement of hand grip strength and pulmonary function was not statistically significant (P > 0.05). Subgroup analyses showed that improvements in 6 MWT, fatigue, anxiety, and depression were more pronounced in old patients who received exercise training, while those who received respiratory rehabilitation had more pronounced improvements in pulmonary function and quality of life.

CONCLUSIONS: Old adults with long COVID who underwent rehabilitation interventions experienced significant improvement in functional capacity, fatigue, quality of life, independence in activities of daily living, and mental health outcomes compared with usual/standard care. These findings suggest that screening, management, and rehabilitation interventions for long COVID in older adults should be strengthened to improve their complete health status and functional status, thereby reducing the long-term disease burden caused by long COVID and fostering healthy aging during the post-pandemic era.}, } @article {pmid39237310, year = {2024}, author = {Robinson, A}, title = {Identifying long covid in children … and other research.}, journal = {BMJ (Clinical research ed.)}, volume = {386}, number = {}, pages = {q1912}, doi = {10.1136/bmj.q1912}, pmid = {39237310}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/epidemiology ; Child ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid39237107, year = {2024}, author = {Letícia, A and Neves, RG and Vieira, YP and Gonzales, TN and Marochi, M and Reis, RZ and Machado, KP and Duro, SMS and de Oliveira Saes, M}, title = {Long COVID symptoms and sleep problems: a population-based study.}, journal = {Journal of sleep research}, volume = {}, number = {}, pages = {e14327}, doi = {10.1111/jsr.14327}, pmid = {39237107}, issn = {1365-2869}, support = {21/2551-0000107-0//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; }, abstract = {To investigate the association between symptoms of long-term effects of coronavirus disease 2019 (long COVID) and sleep problems in a sample population from southern Brazil. This cross-sectional study used data from the SULcovid-19 survey, developed in the municipality of Rio Grande, RS, Brazil. The outcome, long COVID, was investigated through the presence of 18 symptoms, and the exposure variable was sleep problems. Poisson regression with robust adjustment for variance was used to estimate crude and adjusted prevalence ratios for the outcome-exposure relationship. Odds ratio was calculated through multinomial regression of the relationship between the number of symptoms of long COVID and sleep problems. Analyses were adjusted for sex, age, marital status, income, body mass index, smoking status, comorbidities, and hospital admission. A total of 2919 adults and older adults were interviewed. The prevalence of long COVID was 48.3% (95% confidence interval [CI] 46.5-50.1%) and sleep problems were reported by 41.2% of the sample (95% CI 39.4-43.0%). Individuals with sleep problems were more likely to exhibit altered sensitivity (prevalence ratio [PR] 3.27; 95% CI 1.96-5.45), nasal congestion (PR 2.75; 95% CI 1.53-4.94), musculoskeletal symptoms (PR 1.75; 95% CI 1.48-2.06), respiratory issues (PR 1.58; 95% CI 1.24-2.01), and one or more symptom of long COVID (PR 1.27; 95% CI 1.15-1.39). Approximately one-half of the population analysed had long COVID, and four of 10 reported experiencing sleep problems. In addition, the sample tended to have experienced a greater number of symptoms compared with those who reported to sleep well.}, } @article {pmid39236463, year = {2024}, author = {Coelho, FMS and Czuma, R and Ticotsky, A and Maley, J and Mullington, JM and Thomas, RJ}, title = {Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.}, journal = {Sleep medicine}, volume = {123}, number = {}, pages = {37-41}, doi = {10.1016/j.sleep.2024.08.030}, pmid = {39236463}, issn = {1878-5506}, mesh = {Humans ; *COVID-19/complications/diagnosis/epidemiology ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Sleep Wake Disorders/epidemiology/etiology/diagnosis ; Adult ; Aged ; Sleep Initiation and Maintenance Disorders/etiology/diagnosis ; SARS-CoV-2 ; Disorders of Excessive Somnolence/etiology/diagnosis ; }, abstract = {INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness.

METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses.

RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity.

CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.}, } @article {pmid39234483, year = {2024}, author = {Wu, K and Van Name, J and Xi, L}, title = {Cardiovascular abnormalities of long-COVID syndrome: Pathogenic basis and potential strategy for treatment and rehabilitation.}, journal = {Sports medicine and health science}, volume = {6}, number = {3}, pages = {221-231}, pmid = {39234483}, issn = {2666-3376}, abstract = {Cardiac injury and sustained cardiovascular abnormalities in long-COVID syndrome, i.e. post-acute sequelae of coronavirus disease 2019 (COVID-19) have emerged as a debilitating health burden that has posed challenges for management of pre-existing cardiovascular conditions and other associated chronic comorbidities in the most vulnerable group of patients recovered from acute COVID-19. A clear and evidence-based guideline for treating cardiac issues of long-COVID syndrome is still lacking. In this review, we have summarized the common cardiac symptoms reported in the months after acute COVID-19 illness and further evaluated the possible pathogenic factors underlying the pathophysiology process of long-COVID. The mechanistic understanding of how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages the heart and vasculatures is critical in developing targeted therapy and preventive measures for limiting the viral attacks. Despite the currently available therapeutic interventions, a considerable portion of patients recovered from severe COVID-19 have reported a reduced functional reserve due to deconditioning. Therefore, a rigorous and comprehensive cardiac rehabilitation program with individualized exercise protocols would be instrumental for the patients with long-COVID to regain the physical fitness levels comparable to their pre-illness baseline.}, } @article {pmid39234310, year = {2024}, author = {Chowdhury, MMH and Fontaine, MN and Lord, SE and Quenum, AJI and Limoges, MA and Rioux-Perreault, C and Lucier, JF and Cliche, DO and Levesque, D and Boisvert, FM and Cantin, AM and Allard-Chamard, H and Menendez, A and Ilangumaran, S and Piché, A and Dionne, IJ and Ramanathan, S}, title = {Impact of a tailored exercise regimen on physical capacity and plasma proteome profile in post-COVID-19 condition.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1416639}, pmid = {39234310}, issn = {1664-042X}, abstract = {BACKGROUND: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases.

METHODS: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated.

RESULTS: Bicep Curl (+15% vs 4%; p = 0.040) and Sit-to-Stand test (STS-30 (+31% vs +11%; p = 0.043)) showed improvement in the exercise group when compared to the non-exercise group. An interaction effect was also observed for the level of physical activity (p =0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response decreasing in the exercise group.

CONCLUSIONS: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.}, } @article {pmid39233251, year = {2024}, author = {Menzies, V and Webb, F and Lyon, DE and Pruinelli, L and Kelly, DL and Jacobs, M}, title = {Anxiety and depression among individuals with long COVID: Associations with social vulnerabilities.}, journal = {Journal of affective disorders}, volume = {367}, number = {}, pages = {286-296}, doi = {10.1016/j.jad.2024.08.214}, pmid = {39233251}, issn = {1573-2517}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anxiety/ethnology ; Anxiety Disorders/ethnology ; *Depression/ethnology ; Employment/statistics & numerical data ; Ethnicity/psychology ; Social Vulnerability ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome/ethnology/psychology ; Racial Groups/psychology ; }, abstract = {BACKGROUND: We examined the association between symptoms of anxiety and depression among individuals with long COVID and five social vulnerabilities (expenses, employment, food insufficiency, housing, and insurance).

METHODS: Data from the Census Bureau's Household Pulse Survey (HPS) detailing COVID incidence, duration, and symptoms between June 1st and November 14th, 2022 contained versions of the Generalized Anxiety Disorder (GAD-2) and the Patient Health Questionnaire (PHQ-2) questionnaires. Associations between anxiety, depression, and the five social vulnerabilities among respondents from different racial and ethnic groups experiencing long COVID were evaluated using generalized binomial logistic regression. Structural equation models tested whether social vulnerabilities mediated the pathway between race/ethnicity and anxiety/depression.

RESULTS: Blacks, Asians/others, and Hispanics with long COVID were significantly more likely to report anxiety and depression and various social vulnerabilities than Whites. Anxiety among Blacks was significantly associated with difficulty with expenses [Odds Ratio (OR) = 1.743, 95 % Confidence Interval (CI) = 1.739, 1.747], employment (OR = 1.519, 95 % CI = 1.516, 1.523), and housing (OR = 1.192, 95 % CI = 1.19, 1.194). Anxiety among Hispanics was significantly associated with food insufficiency (OR = 1.048, 95 % CI = 1.044, 1.052). Depression among Blacks was significantly associated with trouble with expenses (OR = 1.201, 95 % CI = 1.198, 1.205) and employment (OR = 1.129, 95 % CI = 1.127, 1.132). Mediation analysis showed that the number of social vulnerabilities partially mediated the association between race and anxiety.

LIMITATIONS: This retrospective study utilized secondary, observational, self-reported data from the HPS. Therefore, results may not be generalizable outside of the context in which they were collected.

CONCLUSIONS: The development of tailored programs for population health should address the differential associations of anxiety and depression with social difficulties among racial and ethnic groups.}, } @article {pmid39232821, year = {2024}, author = {Sarker, AH and Kabir, MF and Hossain, KMA and Jahan, S and Hossain, MZ and Hossain, T and Ahmed, S and Ahmed, R and Islam, MW and Jahid, IK}, title = {Two-year epidemiology of post-COVID-19 conditions in Bangladesh: a cohort study of post-COVID-19 from 12,925 SARS-CoV-2 cases between July and December 2021-2023 in Bangladesh.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {82}, number = {1}, pages = {148}, pmid = {39232821}, issn = {0778-7367}, support = {23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; 23-FoBST-06//Jashore University of Science and Technology through the University Grants Commission (UGC)/ ; }, abstract = {BACKGROUND: Post-COVID-19 conditions (PCCs), also known as long COVID, is persistently debilitating disorders that need investigation on their incidence, morbidity, and case-fatality rate.

PURPOSE: The objectives of this cohort study were to determine the incidence, characteristics, case-fatality, morbidity, and recovery of post-COVID-19 symptoms throughout a two-year period of observation.

METHODS: This was a population-based cohort study of post-COVID-19 cases among 12,925 SARS-CoV-2 positive individuals in eight administrative districts of Bangladesh between July and December 2021-2023. PCC was diagnosed according to WHO clinical diagnostic criteria, and the screening procedure was completed through a household screening process.

RESULTS: The incidence of PCC was 3.6%, the case-fatality rate was 1.92%, and the recovery rate was 9.0%. The significant predictors of PCC morbidity were geographical distribution, vaccination, comorbidities, and a longer duration of symptoms or multiple symptoms (p < 0.05).

CONCLUSION: Nearly 465 out of 522 people suffering from PCC are persistent and have a significant disability. However, the rate of recovery was 9.0%. It is necessary to investigate approaches to improve the recovery of PCC in Bangladesh.}, } @article {pmid39232616, year = {2024}, author = {Abu Jawdeh, BG and Vikram, HR}, title = {Coronavirus Disease 2019 in Kidney Transplantation - A 2024 Update.}, journal = {Advances in kidney disease and health}, volume = {31}, number = {5}, pages = {458-465}, doi = {10.1053/j.akdh.2024.03.004}, pmid = {39232616}, issn = {2949-8139}, mesh = {Humans ; *Kidney Transplantation ; *COVID-19/epidemiology/prevention & control/immunology ; SARS-CoV-2 ; Telemedicine ; COVID-19 Vaccines/administration & dosage ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 has led to the death of about 7 million people worldwide. When infected, older individuals and those with diabetes, hypertension, cardiovascular disease, and compromised immune system are at higher risk for unfavorable outcomes. These comorbidities are prevalent in kidney transplant candidates and recipients making them inherently vulnerable to severe acute respiratory syndrome coronavirus 2 infection, hence, the significant burden the pandemic has exerted on kidney transplant programs. With the swift discovery and wide-scale availability of vaccines and therapeutics against severe acute respiratory syndrome coronavirus 2, the pandemic is currently behind us allowing transplant programs to relieve their restrictions and resume normal pre-COVID-19 operations. In the aftermath of the pandemic, we discuss the implications for immunosuppression and vaccination, COVID-19-induced kidney injury phenotypes and long COVID-19 symptoms. We also discuss some of the operational aspects the pandemic brought about - mainly the utilization of telemedicine - that are now here to stay.}, } @article {pmid39232147, year = {2024}, author = {Lakshmikanth, T and Consiglio, C and Sardh, F and Forlin, R and Wang, J and Tan, Z and Barcenilla, H and Rodriguez, L and Sugrue, J and Noori, P and Ivanchenko, M and Piñero Páez, L and Gonzalez, L and Habimana Mugabo, C and Johnsson, A and Ryberg, H and Hallgren, Å and Pou, C and Chen, Y and Mikeš, J and James, A and Dahlqvist, P and Wahlberg, J and Hagelin, A and Holmberg, M and Degerblad, M and Isaksson, M and Duffy, D and Kämpe, O and Landegren, N and Brodin, P}, title = {Immune system adaptation during gender-affirming testosterone treatment.}, journal = {Nature}, volume = {633}, number = {8028}, pages = {155-164}, pmid = {39232147}, issn = {1476-4687}, mesh = {Adult ; Female ; Humans ; Male ; Datasets as Topic ; Dendritic Cells/immunology/metabolism/drug effects ; Immune System/drug effects/metabolism ; Interferon Type I/immunology/metabolism ; Interferon-gamma/immunology/metabolism ; Interleukin-15/immunology/metabolism ; Killer Cells, Natural/immunology/drug effects ; Monocytes/immunology/drug effects/metabolism ; NF-kappa B/metabolism ; Sex Characteristics ; *Testosterone/adverse effects/immunology/pharmacology/therapeutic use ; *Transgender Persons ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID[1], similar to observations in other infections[2]. Females respond more strongly to vaccines, and adverse reactions are more frequent[3], like most autoimmune diseases[4]. Immunological sex differences stem from genetic, hormonal and behavioural factors[5] but their relative importance is only partially understood[6-8]. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.}, } @article {pmid39232125, year = {2024}, author = {Rosa-Souza, FJ and Freire, YA and Galliano, LM and Dalton-Alves, F and de Lima Pinto, JCB and Godtsfriedt, CES and Delevatti, RS and Gerage, AM and Rech, CR and Ritti-Dias, RM and Costa, EC}, title = {Association of physical symptoms with accelerometer-measured movement behaviors and functional capacity in individuals with Long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20652}, pmid = {39232125}, issn = {2045-2322}, support = {0057/2022.//Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES) through the EDITAL IMPACTOS DA PANDEMIA/ ; }, mesh = {Humans ; Male ; Female ; *Accelerometry ; *COVID-19/physiopathology/complications ; Cross-Sectional Studies ; Middle Aged ; *Fatigue/physiopathology ; *Exercise ; Aged ; *Dyspnea/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation & purification ; Movement ; Surveys and Questionnaires ; Myalgia/physiopathology ; Adult ; }, abstract = {Long COVID has been linked to a decline in physical activity and functional capacity. However, it remains unclear which physical symptoms are associated with specific aspects of movement behaviors and functional capacity. We aimed to investigate the associations of fatigue, dyspnea, post-exertional malaise, myalgia, and the co-occurrence of symptoms with movement behaviors and functional capacity in individuals with Long COVID. A cross-sectional multicenter study was conducted. Questionnaires were used to assess fatigue, dyspnea, post-exertional malaise, and myalgia. Accelerometry was employed to assess sedentary time, steps per day, light physical activity, and moderate-to-vigorous physical activity. The six-minute walk test, 30-s chair stand test, and timed up and go were used to assess functional capacity. One hundred and two community-dwelling individuals who had been living with Long COVID for 15 ± 10 months participated in the study. Fatigue, post-exertional malaise, and the co-occurrence of physical symptoms showed a negative association with step count, while post-exertional malaise was also negatively associated with moderate-to-vigorous physical activity. Dyspnea showed a negative association with the functional score, including all tests. Our findings suggest that fatigue, post-exertional malaise, and the co-occurrence of physical symptoms are negatively associated with physical activity, while dyspnea is negatively associated with functional capacity in individuals with Long COVID.}, } @article {pmid39228407, year = {2024}, author = {Sunkersing, D and Goodfellow, H and Mu, Y and Ramasawmy, M and Murali, M and Adams, L and FitzGerald, TJ and Blandford, A and Stevenson, F and Bindman, J and Robson, C and Banerjee, A}, title = {Long COVID symptoms and demographic associations: A retrospective case series study using healthcare application data.}, journal = {JRSM open}, volume = {15}, number = {7}, pages = {20542704241274292}, pmid = {39228407}, issn = {2054-2704}, abstract = {OBJECTIVES: To investigate long COVID (LC) symptoms self-reported via a digital application. Explore associations between various demographic factors and intensity of LC symptoms.

DESIGN: A retrospective case series study. We analysed self-reported symptoms from 1008 individuals with LC between November 30, 2020, and March 23, 2022.

SETTING: England and Wales.

PARTICIPANTS: Individuals with LC using the healthcare application in 31 post-COVID-19 clinics and self-reporting LC symptoms.

MAIN OUTCOME MEASURES: Highest reported LC symptoms, associations with demographic factors and intensity of symptoms.

RESULTS: 109 symptom categories were identified, with pain (26.5%), neuropsychological issues (18.4%), fatigue (14.3%) and dyspnoea (7.4%) the most prevalent. The intensity of reported symptoms increased by 3.3% per month since registration. Age groups 68-77 and 78-87 experienced higher symptom intensity (32.8% and 86% higher, respectively) compared to the 18-27 age group. Women reported 9.2% more intense symptoms than men, and non-white individuals with LC reported 23.5% more intense symptoms than white individuals with LC. Higher education levels (national vocational qualification (NVQ) 3 to NVQ 5) were associated with less symptom intensity (27.7%, 62.8% and 44.7% less, respectively) compared to the least educated (NVQ 1-2). People in less deprived areas had less intense symptoms than those in the most deprived area. No significant association was found between index of multiple deprivation (IMD) decile and number of symptoms.

CONCLUSION: Treatment plans must prioritise addressing prevalent LC symptoms; we recommend sustained support for LC clinics. Demographic factors significantly influence symptom severity, underlining the need for targeted interventions. These findings can inform healthcare policies to better manage LC.}, } @article {pmid39226091, year = {2024}, author = {Valdivieso-Martinez, B and Lopez-Sanchez, V and Sauri, I and Diaz, J and Calderon, JM and Gas-Lopez, ME and Lidon, L and Philibert, J and Lopez-Hontangas, JL and Navarro, D and Cuenca, L and Forner, MJ and Redon, J}, title = {Impact of Long SARS-CoV-2 Omicron Infection on the Health Care Burden: Comparative Case-Control Study Between Omicron and Pre-Omicron Waves.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e53580}, pmid = {39226091}, issn = {2369-2960}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Male ; Case-Control Studies ; Female ; Adult ; Adolescent ; Retrospective Studies ; Middle Aged ; Child ; Young Adult ; Aged ; SARS-CoV-2 ; Child, Preschool ; COVID-19 Vaccines/administration & dosage ; Pandemics ; Cost of Illness ; Infant ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Following the initial acute phase of COVID-19, health care resource use has escalated among individuals with SARS-CoV-2 infection.

OBJECTIVE: This study aimed to compare new diagnoses of long COVID and the demand for health services in the general population after the Omicron wave with those observed during the pre-Omicron waves, using similar assessment protocols for both periods and to analyze the influence of vaccination.

METHODS: This matched retrospective case-control study included patients of both sexes diagnosed with acute SARS-CoV-2 infection using reverse transcription polymerase chain reaction or antigen tests in the hospital microbiology laboratory during the pandemic period regardless of whether the patients were hospitalized. We included patients of all ages from 2 health care departments that cover 604,000 subjects. The population was stratified into 2 groups, youths (<18 years) and adults (≥18 years). Patients were followed-up for 6 months after SARS-CoV-2 infection. Previous vaccination, new diagnoses, and the use of health care resources were recorded. Patients were compared with controls selected using a prospective score matched for age, sex, and the Charlson index.

RESULTS: A total of 41,577 patients with a history of prior COVID-19 infection were included, alongside an equivalent number of controls. This cohort encompassed 33,249 (80%) adults aged ≥18 years and 8328 (20%) youths aged <18 years. Our analysis identified 40 new diagnoses during the observation period. The incidence rate per 100 patients over a 6-month period was 27.2 for vaccinated and 25.1 for unvaccinated adults (P=.09), while among youths, the corresponding rates were 25.7 for vaccinated and 36.7 for unvaccinated individuals (P<.001). Overall, the incidence of new diagnoses was notably higher in patients compared to matched controls. Additionally, vaccinated patients exhibited a reduced incidence of new diagnoses, particularly among women (P<.001) and younger patients (P<.001) irrespective of the number of vaccine doses administered and the duration since the last dose. Furthermore, an increase in the use of health care resources was observed in both adult and youth groups, albeit with lower figures noted in vaccinated individuals. In the comparative analysis between the pre-Omicron and Omicron waves, the incidence of new diagnoses was higher in the former; however, distinct patterns of diagnosis were evident. Specifically, depressed mood (P=.03), anosmia (P=.003), hair loss (P<.001), dyspnea (<0.001), chest pain (P=.04), dysmenorrhea (P<.001), myalgia (P=.011), weakness (P<.001), and tachycardia (P=.015) were more common in the pre-Omicron period. Similarly, health care resource use, encompassing primary care, specialist, and emergency services, was more pronounced in the pre-Omicron wave.

CONCLUSIONS: The rise in new diagnoses following SARS-CoV-2 infection warrants attention due to its potential implications for health systems, which may necessitate the allocation of supplementary resources. The absence of vaccination protection presents a challenge to the health care system.}, } @article {pmid39225854, year = {2024}, author = {Kepp, KP and Bardosh, K and De Bie, T and Emilsson, L and Greaves, J and Lallukka, T and Muka, T and Rangel, JC and Sandström, N and Schippers, MC and Schmidt-Chanasit, J and Vaillancourt, T}, title = {Zero-covid advocacy during the COVID-19 pandemic: a case study of views on Twitter/X.}, journal = {Monash bioethics review}, volume = {42}, number = {2}, pages = {169-199}, pmid = {39225854}, issn = {1836-6716}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; *Social Media ; *SARS-CoV-2 ; *Pandemics ; }, abstract = {During the COVID-19 pandemic, many advocacy groups and individuals criticized governments on social media for doing either too much or too little to mitigate the pandemic. In this article, we review advocacy for COVID-19 elimination or "zero-covid" on the social media platform X (Twitter). We present a thematic analysis of tweets by 20 influential co-signatories of the World Health Network letter on ten themes, covering six topics of science and mitigation (zero-covid, epidemiological data on variants, long-term post-acute sequelae (Long COVID), vaccines, schools and children, views on monkeypox/Mpox) and four advocacy methods (personal advice and promoting remedies, use of anecdotes, criticism of other scientists, and of authorities). The advocacy, although timely and informative, often appealed to emotions and values using anecdotes and strong criticism of authorities and other scientists. Many tweets received hundreds or thousands of likes. Risks were emphasized about children's vulnerability, Long COVID, variant severity, and Mpox, and via comparisons with human immunodeficiency viruses (HIV). Far-reaching policies and promotion of remedies were advocated without systematic evidence review, or sometimes, core field expertise. We identified potential conflicts of interest connected to private companies. Our study documents a need for public health debates to be less polarizing and judgmental, and more factual. In order to protect public trust in science during a crisis, we suggest the development of mechanisms to ensure ethical guidelines for engagement in "science-based" advocacy, and consideration of cost-benefit analysis of recommendations for public health decision-making.}, } @article {pmid39223870, year = {2024}, author = {Mehrotra-Varma, S and Lu, JY and Boparai, MS and Henry, S and Wang, SH and Duong, TQ}, title = {Patients with type 1 diabetes are at elevated risk of developing new hypertension, chronic kidney disease and diabetic ketoacidosis after COVID-19: Up to 40 months' follow-up.}, journal = {Diabetes, obesity & metabolism}, volume = {26}, number = {11}, pages = {5368-5375}, doi = {10.1111/dom.15900}, pmid = {39223870}, issn = {1463-1326}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Diabetic Ketoacidosis/epidemiology ; *Diabetes Mellitus, Type 1/complications/epidemiology ; Female ; Male ; *Hypertension/epidemiology/complications ; *Renal Insufficiency, Chronic/epidemiology/complications ; Adult ; Middle Aged ; Incidence ; Follow-Up Studies ; SARS-CoV-2 ; Risk Factors ; Retrospective Studies ; }, abstract = {AIM: The aim was to investigate whether COVID-19 increases new incidence of hypertension (HTN), chronic kidney disease (CKD) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) up to 40 months post-infection.

MATERIALS AND METHODS: Three groups of patients from the Montefiore Health System in the Bronx (1 March 2020 to 1 July 2023) were studied: T1D patients hospitalized for COVID-19 (H-COVID-19, n = 511), T1D patients with COVID-19 but not hospitalized for COVID-19 (NH-COVID-19, n = 306) and T1D patients without a positive COVID-19 test on record (non-COVID-19, n = 1547). COVID-19 patients were those with a positive polymerase-chain-reaction test on record, and non-COVID-19 patients were either tested negative or not tested on record. Cumulative incidences and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were computed with adjustment for competing risks.

RESULTS: Compared to non-COVID-19 patients, both H-COVID-19 (unadjusted 19.72% vs. 3.14%, p < 0.001; aHR = 7.55 [3.33, 17.06], p < 0.001) and NH-COVID-19 (10.26% vs. 3.14%, p = 0.004; aHR = 5.08 [2.19, 11.78], p < 0.001) patients were more likely to develop new HTN. Compared to non-COVID-19 patients, both H-COVID-19 (11.41% vs. 1.14%, p < 0.001; aHR = 9.76 [4.248, 22.25], p < 0.001) and NH-COVID-19 (7.69% vs. 1.14%, p < 0.001; aHR = 6.54 [2.91, 14.67], p < 0.001) patients were more likely to develop new CKD. Compared to non-COVID-19 patients, both H-COVID-19 (4.09% vs. 1.06%, p < 0.001; aHR = 12.24 [4.09, 36.59], p < 0.001) and NH-COVID-19 (3.06% vs. 1.06%, p = 0.035; aHR = 12.94 [4.09, 40.89], p < 0.001) patients were more likely to develop new DKA at follow-up.

CONCLUSION: T1D patients with COVID-19 are at higher risk of developing new HTN, CKD and DKA compared to T1D patients without COVID-19.}, } @article {pmid39223825, year = {2024}, author = {Clausen, TM and Fargen, KM and Primiani, CT and Sattur, M and Amans, MR and Hui, FK}, title = {Post-acute sequelae of COVID infection and cerebral venous outflow disorders: Overlapping symptoms and mechanisms?.}, journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences}, volume = {}, number = {}, pages = {15910199241273946}, pmid = {39223825}, issn = {2385-2011}, abstract = {Neurological long Covid (NLC) is a major post-acute sequela of SARS-CoV-2 infection, affecting up to 10% of infected patients. The clinical presentation of patients with NLC is varied, but general NLC symptoms have been noted to closely mimic symptoms of cerebral venous outflow disorders (CVD). Here we review key literature and discuss evidence supporting this comparison. We also aimed to describe the similarity between CVD symptomatology and neuro-NLC symptoms from two perspectives: a Twitter-distributed survey for long covid sufferers to estimate nature and frequency of neurological symptoms, and through a small cohort of patients with long covid who underwent CVD work up per our standard workflow. Over 700 patients responded, and we argue that there is a close symptom overlap with those of CVD. CVD workup in a series of 6 patients with neurological long COVID symptoms showed jugular vein stenosis by CT venography and varying degrees of increased intracranial pressure. Finally, we discuss the potential pathogenic association between vascular inflammation, associated with COVID-19 infection, venous outflow congestion, and its potential involvement in NLC.}, } @article {pmid39223749, year = {2024}, author = {Wechsler, JB and Berken, JA and Keeley, K and Singer, W and Jhaveri, R and Katz, BZ and Fortunato, JE and Saps, M}, title = {Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID-19.}, journal = {Neurogastroenterology and motility}, volume = {36}, number = {11}, pages = {e14909}, doi = {10.1111/nmo.14909}, pmid = {39223749}, issn = {1365-2982}, support = {//Campaign Urging Research for Eosinophilic Disease/ ; }, mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; Child ; Adolescent ; Female ; Male ; *Gastrointestinal Diseases/psychology/diagnosis ; *Severity of Illness Index ; Quality of Life ; SARS-CoV-2 ; Cohort Studies ; Surveys and Questionnaires ; Nausea/physiopathology ; Brain-Gut Axis ; }, abstract = {BACKGROUND: Post-infectious disorders of gut-brain interaction (PI-DGBI) have significant impact on children and adolescents. The effect of COVID-19 on PI-DGBI-associated symptoms in this population, however, is unknown.

METHODS: We performed electronic medical record searches to identify patients 8-17 years old with a SARS-CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April-October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms-Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID-19 test or the test result.

RESULTS: One hundred and ninety-six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self-reported their child's COVID-19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID-19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID-19 testing that was highest among patients with a positive COVID-19 test. Abdominal pain and diarrhea prior to COVID-19 testing predicted higher NP scores.

CONCLUSIONS: Among symptomatic COVID-19 tested children, we found increased severity of nausea-associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID-19 test.}, } @article {pmid39221567, year = {2024}, author = {Kooner, HK and Wyszkiewicz, PV and Matheson, AM and McIntosh, MJ and Abdelrazek, M and Dhaliwal, I and Nicholson, JM and Kirby, M and Svenningsen, S and Parraga, G}, title = {Chest CT Airway and Vascular Measurements in Females with COPD or Long-COVID.}, journal = {COPD}, volume = {21}, number = {1}, pages = {2394129}, doi = {10.1080/15412555.2024.2394129}, pmid = {39221567}, issn = {1541-2563}, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; Ex-Smokers ; Lung/blood supply/diagnostic imaging/physiopathology ; *Pulmonary Disease, Chronic Obstructive/diagnostic imaging/physiopathology ; *Quality of Life ; *Tomography, X-Ray Computed ; Post-Acute COVID-19 Syndrome/diagnostic imaging/physiopathology ; Longitudinal Studies ; Prospective Studies ; }, abstract = {Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID. Our objective was to evaluate CT airway and pulmonary vascular and quality-of-life measurements in females with COPD as compared to ex-smokers and patients with long-COVID. Chest CT was acquired 3-months post-COVID-19 infection in females with long-COVID for comparison with the same inspiratory CT in female ex-smokers and COPD patients. TAC, LA, WT, and pulmonary vascular measurements were quantified. Linear regression models were adjusted for confounders including age, height, body-mass-index, lung volume, pack-years and asthma diagnosis. Twenty-one females (53 ± 14 years) with long-COVID, 17 female ex-smokers (69 ± 9 years) and 13 female COPD (67 ± 6 years) patients were evaluated. In the absence of differences in quality-of-life scores, females with long-COVID reported significantly different LA (p = 0.006) compared to ex-smokers but not COPD (p = 0.7); WT% was also different compared to COPD (p = 0.009) but not ex-smokers (p = 0.5). In addition, there was significantly greater pulmonary small vessel volume (BV5) in long-COVID as compared to female ex-smokers (p = 0.045) and COPD (p = 0.003) patients and different large (BV10) vessel volume as compared to COPD (p = 0.03). In females with long-COVID and highly abnormal quality-of-life scores, there was CT evidence of airway remodelling, similar to ex-smokers and patients with COPD, but there was no evidence of pulmonary vascular remodelling.Clinical Trial Registration: www.clinicaltrials.gov NCT05014516 and NCT02279329.}, } @article {pmid39221194, year = {2024}, author = {McAlearney, AS and Eiterman, LP and Mayers, E and Eramo, JL and MacEwan, SR}, title = {A Journey Through Grief: Experiences of Loss Among Patients With Long COVID.}, journal = {Journal of patient experience}, volume = {11}, number = {}, pages = {23743735241272267}, pmid = {39221194}, issn = {2374-3735}, abstract = {Long COVID is a growing health concern with data continuing to emerge about the psychosocial consequences of this new chronic condition. We aimed to improve understanding of the experiences of patients with Long COVID, focusing on emotional impacts arising from experiences of loss and grief caused by persistent physical symptoms and changes in lifestyle and social support. Patients (n = 21) were recruited August to September 2022 from a post-COVID recovery clinic to participate in semistructured interviews. We found that Long COVID patients (1) reported experiencing loss across multiple domains including loss of physical health, mental health, social support and connections, roles in their families, and self-identities, and (2) described experiences of grief that mirrored the 5 stages of grief in the Kubler-Ross model: denial, anger, bargaining, depression, and for some, acceptance. Our findings highlight the importance of evaluating the experiences of loss and grief among Long COVID patients as well as support systems for this patient population. Providers may be encouraged to incorporate mental health and bereavement support resources to address critical needs of Long COVID patients.}, } @article {pmid39221179, year = {2024}, author = {Galgut, O and Ashford, F and Deeks, A and Ghataure, A and Islam, M and Sambhi, T and Ker, YW and Duncan, CJA and de Silva, TI and Hopkins, S and Hall, V and Klenerman, P and Dunachie, S and Richter, A}, title = {COVID-19 vaccines are effective at preventing symptomatic and severe infection among healthcare workers: A clinical review.}, journal = {Vaccine: X}, volume = {20}, number = {}, pages = {100546}, pmid = {39221179}, issn = {2590-1362}, abstract = {INTRODUCTION: Health care workers (HCWs) have been at increased risk of infection during the SARS-CoV-2 pandemic and as essential workers have been prioritised for vaccination. Due to increased exposure HCW are considered a predictor of what might happen in the general population, particularly working age adults. This study aims to summarise effect of vaccination in this 'at risk' cohort.

METHODS: Ovid MEDLINE and Embase were searched, and 358 individual articles were identified. Of these 49 met the inclusion criteria for review and 14 were included in a meta-analysis.

RESULTS: Participants included were predominantly female and working age. Median time to infection was 51 days. Reported vaccine effectiveness against infection, symptomatic infection, and infection requiring hospitalisation were between 5 and 100 %, 34 and 100 %, and 65 and 100 % (respectively). No vaccinated HCW deaths were recorded in any study. Pooled estimates of protection against infection, symptomatic infection, and hospitalisation were, respectively, 84.7 % (95 % CI 72.6-91.5 %, p < 0.0001), 86.0 % (95 % CI 67.2 %-94.0 %; p < 0.0001), and 96.1 % (95 % CI 90.4 %-98.4 %). Waning protection against infection was reported by four studies, although protection against hospitalisation for severe infection persists for at least 6 months post vaccination.

CONCLUSIONS: Vaccination against SARS-CoV2 in HCWs is protective against infection, symptomatic infection, and hospitalisation. Waning protection is reported but this awaits more mature studies to understand durability more clearly. This study is limited by varying non-pharmacological responses to COVID-19 between included studies, a predominantly female and working age population, and limited information on asymptomatic transmission or long COVID protection.}, } @article {pmid39220656, year = {2024}, author = {Griffin, DO}, title = {Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae462}, pmid = {39220656}, issn = {2328-8957}, abstract = {While the acute manifestations of infectious diseases are well known, in some individuals, symptoms can either persist or appear after the acute period. Postviral fatigue syndromes are recognized with other viral infections and are described after coronavirus disease 2019 (COVID-19). We have a growing number of individuals with symptoms that persist for weeks, months, and years. Here, we share the evidence regarding the abnormalities associated with postacute sequelae of COVID-19 (PASC) and therapeutics. We describe physiological and biochemical abnormalities seen in individuals reporting PASC. We describe the several evidence-based interventions to offer patients. It is expected that this growing understanding of the mechanisms driving PASC and the benefits seen with certain therapeutics may not only lead to better outcomes for those with PASC but may also have the potential for understanding and treating other postinfectious sequelae.}, } @article {pmid39220224, year = {2024}, author = {Liu, X and Pan, F and Wang, Q and Wang, S and Zhang, J}, title = {Traditional Chinese Rehabilitation Exercise (TCRE) for Myofascial Pain: Current Evidence and Further Challenges.}, journal = {Journal of pain research}, volume = {17}, number = {}, pages = {2801-2810}, pmid = {39220224}, issn = {1178-7090}, abstract = {Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.}, } @article {pmid39218998, year = {2024}, author = {Cheng, X and Cao, M and Yeung, WF and Cheung, DST}, title = {The effectiveness of exercise in alleviating long COVID symptoms: A systematic review and meta-analysis.}, journal = {Worldviews on evidence-based nursing}, volume = {21}, number = {5}, pages = {561-574}, doi = {10.1111/wvn.12743}, pmid = {39218998}, issn = {1741-6787}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; Dyspnea ; Exercise ; *Exercise Therapy/methods ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long COVID is prevalent in the general population. Exercise is a promising component of rehabilitation for long COVID patients.

AIM: This study examined the effects of exercise interventions on managing long COVID symptoms.

METHODS: In this systematic review and meta-analysis, a systematic search was conducted through June 2023 using keywords such as "long COVID" and "post-acute COVID-19 syndrome" among major electronic databases. Randomized controlled trials that examined the effect of exercise on patients suffering from long COVID were included. Nine studies involving 672 individuals were included in this study.

RESULTS: The main outcomes for exercise interventions in patients with long COVID were fatigue, dyspnea, anxiety, depression, and cognitive impairment. The exercise interventions comprised aerobic exercise, multimodal exercise, breathing exercise, and Taichi. Most of the included studies (6/9) were at high risk of bias. According to the meta-analyses, exercise significantly improved long COVID fatigue (ES = 0.89, 95% CI: 0.27 to 1.50) and dyspnea (ES = 1.21, 95% CI [0.33, 2.09]), whereas no significant effect was identified on long COVID anxiety, depression, and cognitive impairment. According to subgroup analyses, multimodal exercise had the broadest spectrum of benefits on long COVID symptoms (including fatigue, dyspnea, and depression), and supervised exercise, intervention frequency ≤4 times a week, the passive control group also showed a positive effect on some long COVID symptoms.}, } @article {pmid39218877, year = {2024}, author = {Ma, S and Wei, D and Hu, W and Xi, M and Zhang, Y and Chen, X and Chen, J}, title = {A case report of prolonged viral shedding of SARS-CoV-2 in a patient who receive ibrutinib for CLL therapy.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {895}, pmid = {39218877}, issn = {1471-2334}, mesh = {Female ; Humans ; *Adenine/analogs & derivatives/therapeutic use ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; *COVID-19/virology ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; *Piperidines/therapeutic use ; Pyrazoles/therapeutic use ; Pyrimidines/therapeutic use ; *SARS-CoV-2 ; *Virus Shedding ; }, abstract = {Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.}, } @article {pmid39217829, year = {2024}, author = {Steinmann, LA and Claaß, LV and Rau, M and Massag, J and Diexer, S and Klee, B and Gottschick, C and Binder, M and Sedding, D and Frese, T and Girndt, M and Hoell, J and Moor, I and Rosendahl, J and Gekle, M and Mikolajczyk, R and Opel, N}, title = {Differential associations between SARS-CoV-2 infection, perceived burden of the pandemic and mental health in the German population-based cohort for digital health research.}, journal = {Psychiatry research}, volume = {341}, number = {}, pages = {116140}, doi = {10.1016/j.psychres.2024.116140}, pmid = {39217829}, issn = {1872-7123}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Germany/epidemiology ; Male ; Female ; Middle Aged ; Adult ; *Mental Health ; Aged ; Cohort Studies ; SARS-CoV-2 ; Young Adult ; Cost of Illness ; Surveys and Questionnaires ; Retrospective Studies ; Pandemics ; Digital Health ; }, abstract = {Understanding the potential adverse effects of the COVID-19-pandemic on mental health remains a challenge for public health. Differentiation between potential consequences of actual infection with SARS-CoV-2 and the subjective burden of the pandemic due to measures and restrictions to daily life still remains elusive. Therefore, we investigated the differential association between infection with SARS-Cov-2 and subjective burden of the pandemic in a study cohort of 7601 participants from the German population-based cohort for digital health research (DigiHero), who were recruited between March 4th and April 25th 2022. Data was collected using the online survey tool LimeSurvey® between March and October 2022 in consecutive surveys, which included questionnaires on infection status and symptoms following COVID-19 as well as retrospective assessment of the subjective burden of the pandemic. We observed an association of a past SARS-CoV-2 infection on deteriorated mental health related symptoms, whereas no association or interaction with burden of the pandemic occurred. The association was driven by participants with persistent symptoms 12 weeks after infection. On a symptom specific level, neuropsychiatric symptoms such as exhaustion and fatigue, concentration deficits and problems with memory function were the primary drivers of the association with small effect sizes between 0.048 and 0.062 ηp[2].}, } @article {pmid39215662, year = {2024}, author = {Martins, BAA and Garcia, ALH and Borges, MS and Picinini, J and Serpa, ET and Nobles, DDR and Silva, LL and Dalberto, D and Hansen, AW and Spilki, FR and Schuler-Faccini, L and Rampelotto, PH and Da Silva, J}, title = {Exploring the relationship between genetic instability and health outcomes in acute and chronic post-COVID syndrome.}, journal = {Mutagenesis}, volume = {39}, number = {6}, pages = {287-300}, doi = {10.1093/mutage/geae022}, pmid = {39215662}, issn = {1464-3804}, support = {408831/2022-7//National Council for Scientific and Technological Development/ ; }, mesh = {Humans ; Male ; Female ; *COVID-19/genetics/psychology/complications/epidemiology ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Genomic Instability ; Adult ; *SARS-CoV-2 ; DNA Damage/genetics ; Chronic Disease ; Aged ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae.}, } @article {pmid39211818, year = {2024}, author = {Jacobs, M and Ellis, C and Estores, I}, title = {Multilevel Determinants of Long COVID and Potential for Telehealth Intervention.}, journal = {Ethnicity & disease}, volume = {34}, number = {3}, pages = {155-164}, pmid = {39211818}, issn = {1945-0826}, mesh = {Humans ; *Telemedicine ; Female ; Male ; Middle Aged ; *COVID-19/epidemiology ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; Young Adult ; Adolescent ; Social Determinants of Health ; SARS-CoV-2 ; Socioeconomic Factors ; Internet Use/statistics & numerical data ; }, abstract = {BACKGROUND: Post-coronavirus disease 2019 (COVID-19) syndrome, or long COVID, has a variety of symptoms, but little is known about the condition. This study evaluated the association between individual factors, social determinants of health, and the likelihood of long COVID by assessing internet usage as an indicator of viable access to telehealth.

METHODS: Data from the 2022 National Health Interview Survey identified adults who (1) reported a previous COVID-19-positive test and/or diagnosis and (2) experienced long COVID. A 2-stage selection model predicted COVID-19 infection in the first stage and long COVID in the second stage. To test the potential use of telehealth, binary dependent variable regression evaluated internet usage among respondents with long COVID.

RESULTS: About 40% (N=10,318) of respondents had tested positive/been diagnosed with COVID-19, but less than 20% of them (N=1797) had long COVID. Although older respondents were less likely to have COVID (odds ratio [OR]=0.48; 95% confidence interval [CI]=0.44, 0.53), they were more likely to experience long COVID (OR=1.63; CI=1.37, 1.93). Relative to White individuals, Black individuals were less likely to have COVID (OR=0.78; CI=0.69, 0.89) but significantly more likely (OR=1.21; CI=1.09, 1.64) to experience long COVID. Long COVID was also more likely among low-income earners (first income-to-poverty ratio quartile OR=1.40, CI=1.14, 1.72; second income-to-poverty ratio OR=1.37, CI=1.14, 1.64) and those without a college degree (OR=1.42; CI=1.01, 1.66). There were no statistically significant differences in internet access between racial, geographic, or income groups.

CONCLUSION: Long COVID is significantly more likely among Black individuals and low-income households than among their counterparts, but with few recourses available, telehealth service delivery could be a feasible intervention mechanism.}, } @article {pmid39215197, year = {2024}, author = {Britton, PN and Burrell, R and Chapman, E and Boyle, J and Alexander, S and Belessis, Y and Dalby-Payne, J and Knight, K and Lau, C and McMullan, B and Milne, B and Paull, M and Nguyen, J and Selvadurai, H and Dale, R and Baillie, A}, title = {Post COVID-19 conditions in an Australian pediatric cohort, 3 months following a Delta outbreak.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {39215197}, issn = {1530-0447}, abstract = {BACKGROUND: Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents.

METHODS: The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment.

FINDINGS: 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID.

INTERPRETATION: During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention.

IMPACT: Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity.}, } @article {pmid39214645, year = {2024}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Nirmatrelvir/Ritonavir Compared With Placebo/Ritonavir for Long COVID: A Comment.}, journal = {The American journal of medicine}, volume = {137}, number = {9}, pages = {e173}, doi = {10.1016/j.amjmed.2024.05.007}, pmid = {39214645}, issn = {1555-7162}, mesh = {Humans ; *Ritonavir/therapeutic use ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; }, } @article {pmid39214528, year = {2024}, author = {Gunter, J}, title = {The vacuum of information about covid's prevalence puts me at risk-bring back better data collection.}, journal = {BMJ (Clinical research ed.)}, volume = {386}, number = {}, pages = {q1905}, doi = {10.1136/bmj.q1905}, pmid = {39214528}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Prevalence ; *SARS-CoV-2 ; Data Collection/methods/standards ; }, } @article {pmid39214242, year = {2024}, author = {Foulkes, S and Evans, J and Neill, C and Bishop, J and Khawam, J and Islam, J and Atti, A and Brown, CS and Hopkins, S and Price, L and Hall, V and , }, title = {Prevalence and impact of persistent symptoms following SARS-CoV-2 infection among healthcare workers: A cross-sectional survey in the SIREN cohort.}, journal = {The Journal of infection}, volume = {89}, number = {4}, pages = {106259}, doi = {10.1016/j.jinf.2024.106259}, pmid = {39214242}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Male ; Female ; *Health Personnel/statistics & numerical data ; Prevalence ; Middle Aged ; Adult ; *SARS-CoV-2 ; United Kingdom/epidemiology ; Surveys and Questionnaires ; Cohort Studies ; Vaccination/statistics & numerical data ; COVID-19 Vaccines/administration & dosage ; }, abstract = {INTRODUCTION: Following SARS-CoV-2 infection, some patients experience a range of long-lasting symptoms, with a specific burden on their lives and ability to work.

AIM: We describe the prevalence and impact of persistent symptoms pre-/post-vaccination in SIREN study participants.

METHODS: A cross-sectional study of SARS-CoV-2 positive participants was carried out within SIREN, a frequently tested UK healthcare worker cohort with vaccination and demographic data available. Participants with a SARS-CoV-2 positive PCR or anti-SARS-CoV-2 sample between 01 March 2020 and 31 September 2022 were asked via a questionnaire about symptoms and days absent from work following infection. Responses were excluded if infection dates were inconsistent with study records or missing key data. Symptom type/duration and whether infection occurred pre-/post-vaccination and during which variant period were described. Logistic regression was used to estimate factors associated with persistent symptoms (>12 weeks), adjusting for vaccination and demographic factors. The median days absent from work were also determined.

RESULTS: Of 16,599 invitations, 6677 participants responded, and 5053 were included in the analysis. The prevalence of persistent symptoms (symptoms lasting over 12 weeks) differed by infection episode; highest for first infections (32.7%; 1557/4767) compared to second (21.6%; 214/991) and third infections (21.6%; 16/74). Most frequently reported symptoms were fatigue, tiredness, shortness of breath and difficulty concentrating. A higher prevalence of persistent symptoms was reported during the Wild-type variant period compared to the other variant periods (52.9% Wild-type vs. 20.7% Omicron, for any symptom reported during their first infection). Overall, persistent symptoms were higher among unvaccinated participants (unvaccinated 38.1% vs vaccinated 22.0%). Multivariable analysis showed that participants were less likely to report persistent symptoms in infections occurring after vaccination compared to those with an infection before vaccination in the Alpha/Delta and Omicron periods (Alpha/Delta: adjusted Odds Ratio (aOR) 0.66, CI 95% 0.51-0.87, p = aOR 0.07, CI 95% 0.01-0.65, p = 0.02). About half of participants reported that their persistent symptoms impacted their day-to-day (51.8%) and work-related (42.1%) activities 'a little', and 24.0% and 14.4% reported that the impact was 'A lot'. 8.9% reported they had reduced their working hours, and 13.9% had changed their working pattern.

DISCUSSION: Persistent symptoms were frequent in our cohort, and there was a reduction in symptom duration in those with multiple infection episodes during later variant periods and post-vaccination. The impact of persistent symptoms resulting in reducing working hours or adjusting working patterns has important implications for workforce resilience. UK healthcare workers were highly exposed during the pandemic, demonstrating a significant burden.}, } @article {pmid39214187, year = {2025}, author = {Wee, LE and Lim, JT and Tay, AT and Chiew, CJ and Young, BE and Wong, B and Lim, R and Lee, CL and Tan, J and Vasoo, S and Lye, DC and Tan, KB}, title = {Nirmatrelvir/ritonavir treatment and risk for postacute sequelae of COVID-19 in older Singaporeans.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {1}, pages = {93-100}, doi = {10.1016/j.cmi.2024.08.019}, pmid = {39214187}, issn = {1469-0691}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Antiviral Agents/therapeutic use ; Cardiovascular Diseases/epidemiology ; *COVID-19/epidemiology/complications/prevention & control ; COVID-19 Drug Treatment ; *Drug Combinations ; Lopinavir/therapeutic use ; Retrospective Studies ; Risk Factors ; *Ritonavir/therapeutic use/adverse effects ; Singapore/epidemiology ; }, abstract = {OBJECTIVES: Significant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans.

METHODS: National COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022-4 August 2023). The cohort was divided into nirmatrelvir/ritonavir-treated and untreated groups. Between-group differences in baseline characteristics were adjusted using overlap weighting. Risks of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses and postacute symptoms (31-180 days) after SARS-CoV-2 infection were contrasted in treated/untreated groups using competing risks regressions (adjusted for demographics/vaccination status/comorbidities).

RESULTS: A total of 188 532 older Singaporeans were included; 5.8% (10 905/188 532) received nirmatrelvir/ritonavir. No significantly decreased risk of postacute sequelae (any sequelae: adjusted hazards ratio [aHR], 1.06; 0.94-1.19; cardiovascular sequelae: aHR, 1.01; 0.83-1.24; neurological sequelae: aHR, 1.09; 0.95-1.27; respiratory sequelae: aHR, 1.14; 0.84-1.55; autoimmune sequelae: aHR, 0.76; 0.53-1.09; or any postacute symptom: aHR, 0.97; 0.80-1.18) was observed up to 180 days post-infection in nirmatrelvir/ritonavir-treated individuals vs. untreated cases. Across all vaccination and age subgroups, no significantly decreased risk of any postacute diagnosis/symptom or any cardiovascular, neurological, respiratory, and autoimmune complications up to 180 days post-infection was observed.

DISCUSSION: Early outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.}, } @article {pmid39212724, year = {2024}, author = {Chen, G and Liu, Q and Chen, J and Cai, G and Tan, C and Zhao, Y and Hu, Q and Yang, X and Xu, G and Lan, Y}, title = {Long COVID patients' brain activation is suppressed during walking and severer symptoms lead to stronger suppression.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1887-1901}, pmid = {39212724}, issn = {1433-8491}, support = {2022YFC2009700//Natural Key Research and Development Program of China/ ; 81974357//National Natural Science Foundation of China/ ; 82072548//National Natural Science Foundation of China/ ; 202206010197//Guangzhou Municipal Science and Technology Project/ ; 202201020378//Guangzhou Municipal Science and Technology Project/ ; SL2023A03J00983//Guangzhou Municipal Science and Technology Project/ ; }, mesh = {Humans ; *COVID-19/physiopathology ; Male ; Female ; Middle Aged ; *Walking/physiology ; Cross-Sectional Studies ; Adult ; *Brain/diagnostic imaging/physiopathology ; *Post-Acute COVID-19 Syndrome ; Aged ; Spectroscopy, Near-Infrared ; SARS-CoV-2 ; Cognition/physiology ; Severity of Illness Index ; }, abstract = {This research aims to study the factors contributing to Long COVID and its effects on motor and cognitive brain regions using population surveys and brain imaging. The goal is to provide new insights into the neurological effects of the illness and establish a basis for addressing neuropsychiatric symptoms associated with Long COVID. Study 1 used a cross-sectional design to collect data on demographic characteristics and factors related to Long COVID symptoms in 551 participants. In Study 2, subjects with Long COVID and SARS-CoV-2 uninfected individuals underwent fNIRS monitoring while performing various tasks. Study 1 found that gender, age, BMI, Days since the first SARS-CoV-2 infection, and Symptoms at first onset influenced Long COVID performance. Study 2 demonstrated that individuals in the SARS-CoV-2 uninfected group exhibited greater activation of cognitive function-related brain regions than those in the Long COVID group while performing a level walking task. Furthermore, individuals in the Long COVID group without functional impairment displayed higher activation of brain regions associated with motor function during a weight-bearing walking task than those with functional impairment. Among individuals with Long COVID, those with mild symptoms at onset exhibited increased activation of brain regions linked to motor and cognitive function relative to those with moderate symptoms at onset. Individuals with Long COVID exhibited decreased activation in brain regions associated with cognitive and motor function compared to SARS-CoV-2 uninfected individuals. Moreover, those with more severe initial symptoms or functional impairment displayed heightened inhibition in these brain regions.}, } @article {pmid39212062, year = {2024}, author = {Šmíd, M and Barusová, T and Jarkovský, J and Májek, O and Pavlík, T and Přibylová, L and Weinerová, J and Zajíček, M and Trnka, J}, title = {Post-vaccination, post-infection and hybrid immunity against severe cases of COVID-19 and long COVID after infection with SARS-CoV-2 Omicron subvariants, Czechia, December 2021 to August 2023.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {29}, number = {35}, pages = {}, pmid = {39212062}, issn = {1560-7917}, mesh = {Humans ; *COVID-19/immunology/prevention & control/epidemiology ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology/administration & dosage ; Female ; Male ; Middle Aged ; Vaccination ; Adult ; Czech Republic/epidemiology ; Immunization, Secondary ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BackgroundCOVID-19 remains a major infectious disease with substantial implications for individual and public health including the risk of a post-infection syndrome, long COVID. The continuous changes in dominant variants of SARS-CoV-2 necessitate a careful study of the effect of preventative strategies.AimWe aimed to estimate the effectiveness of post-vaccination, post-infection and hybrid immunity against severe cases requiring oxygen support caused by infections with SARS-CoV-2 variants BA1/2 and BA4/5+, and against long COVID in the infected population and their changes over time.MethodsWe used a Cox regression analysis with time-varying covariates and calendar time and logistic regression applied to national-level data from Czechia from December 2021 until August 2023.ResultsRecently boosted vaccination, post-infection and hybrid immunity provide significant protection against a severe course of COVID-19, while unboosted vaccination more than 10 months ago has a negligible protective effect. The post-vaccination immunity against the BA1/2 or BA4/5+ variants, especially based on the original vaccine types, appears to wane rapidly compared with post-infection and hybrid immunity. Once infected, however, previous immunity plays only a small protective role against long COVID.ConclusionVaccination remains an effective preventative measure against a severe course of COVID-19 but its effectiveness wanes over time thus highlighting the importance of booster doses. Once infected, vaccines may have a small protective effect against the development of long COVID.}, } @article {pmid39211746, year = {2024}, author = {Daodu, TB and Rugel, EJ and Lear, SA}, title = {Impact of Long COVID-19 on Health Outcomes Among Adults With Preexisting Cardiovascular Disease and Hypertension: A Systematic Review.}, journal = {CJC open}, volume = {6}, number = {8}, pages = {939-950}, pmid = {39211746}, issn = {2589-790X}, abstract = {BACKGROUND: This review summarizes the impact of long COVID (LC) on the health of adults with preexisting cardiovascular disease (CVD) and hypertension.

METHODS: We searched Medline, Web of Science (Core Collection), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), without language restrictions, for articles published from December 1, 2019 through October 10, 2023, to ensure all relevant studies were captured. We included studies that enrolled adults (aged ≥18 years) diagnosed with CVD prior to COVID-19 infection whose infection was subsequently determined to be LC per the World Health Organization definition. We excluded studies with adults diagnosed with CVD concurrent with or subsequent to COVID-19 or with those who solely self-reported LC. We used a custom-built data extraction form to collect a range of study characteristics. Study quality was assessed using modified versions of the National Heart, Lung, and Blood Institute quality-assessment tools.

RESULTS: A total of 13,779 studies were identified; 53 were included in the final analysis. Of these, 27 were of good quality and 26 were of fair quality. Health outcomes consisted of the presence of prolonged symptoms of LC (n = 29), physiological health outcomes (n = 20), lifestyle behaviours (n = 19), psycho-social outcomes (n = 13), CVD complications (n = 5), and death and hospital readmission (n = 5). Thirty-four studies incorporated 2 or more outcomes, and 19 integrated only 1.

CONCLUSIONS: Given the significant impact of LC among individuals with preexisting CVD, specially tailored clinical management is needed for members of this population. Additional studies on the impact of LC among those with CVD and other underlying conditions also would be beneficial.}, } @article {pmid39210399, year = {2024}, author = {Fleischmann-Struzek, C and Joost, FEA and Pletz, MW and Weiß, B and Paul, N and Ely, EW and Reinhart, K and Rose, N}, title = {How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature.}, journal = {Critical care (London, England)}, volume = {28}, number = {1}, pages = {283}, pmid = {39210399}, issn = {1466-609X}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Sepsis/complications ; Post-Acute COVID-19 Syndrome ; Critical Care/methods ; Critical Illness ; }, abstract = {Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.}, } @article {pmid39210315, year = {2024}, author = {Gourgoura, K and Rivadeneyra, P and Stanghellini, E and Caroni, C and Bartolucci, F and Curcio, R and Bartoli, S and Ferranti, R and Folletti, I and Cavallo, M and Sanesi, L and Dominioni, I and Santoni, E and Morgana, G and Pasticci, MB and Pucci, G and Vaudo, G}, title = {Modelling the long-term health impact of COVID-19 using Graphical Chain Models brief heading: long COVID prediction by graphical chain models.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {885}, pmid = {39210315}, issn = {1471-2334}, support = {#20414//Fondazione Cassa di Risparmio di Perugia/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Italy/epidemiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Hospitalization ; Survivors ; Risk Factors ; }, abstract = {BACKGROUND: Long-term sequelae of SARS-CoV-2 infection, namely long COVID syndrome, affect about 10% of severe COVID-19 survivors. This condition includes several physical symptoms and objective measures of organ dysfunction resulting from a complex interaction between individual predisposing factors and the acute manifestation of disease. We aimed at describing the complexity of the relationship between long COVID symptoms and their predictors in a population of survivors of hospitalization for severe COVID-19-related pneumonia using a Graphical Chain Model (GCM).

METHODS: 96 patients with severe COVID-19 hospitalized in a non-intensive ward at the "Santa Maria" University Hospital, Terni, Italy, were followed up at 3-6 months. Data regarding present and previous clinical status, drug treatment, findings recorded during the in-hospital phase, presence of symptoms and signs of organ damage at follow-up were collected. Static and dynamic cardiac and respiratory parameters were evaluated by resting pulmonary function test, echocardiography, high-resolution chest tomography (HRCT) and cardiopulmonary exercise testing (CPET).

RESULTS: Twelve clinically most relevant factors were identified and partitioned into four ordered blocks in the GCM: block 1 - gender, smoking, age and body mass index (BMI); block 2 - admission to the intensive care unit (ICU) and length of follow-up in days; block 3 - peak oxygen consumption (VO2), forced expiratory volume at first second (FEV1), D-dimer levels, depression score and presence of fatigue; block 4 - HRCT pathological findings. Higher BMI and smoking had a significant impact on the probability of a patient's admission to ICU. VO2 showed dependency on length of follow-up. FEV1 was related to the self-assessed indicator of fatigue, and, in turn, fatigue was significantly associated with the depression score. Notably, neither fatigue nor depression depended on variables in block 2, including length of follow-up.

CONCLUSIONS: The biological plausibility of the relationships between variables demonstrated by the GCM validates the efficacy of this approach as a valuable statistical tool for elucidating structural features, such as conditional dependencies and associations. This promising method holds potential for exploring the long-term health repercussions of COVID-19 by identifying predictive factors and establishing suitable therapeutic strategies.}, } @article {pmid39209506, year = {2024}, author = {Gartmann, J and Sturm, C and Boekel, A}, title = {Physiotherapy interventions in post- and long-COVID-19: a scoping review protocol.}, journal = {BMJ open}, volume = {14}, number = {8}, pages = {e077420}, pmid = {39209506}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; *Physical Therapy Modalities ; Post-Acute COVID-19 Syndrome/rehabilitation ; Research Design ; Review Literature as Topic ; }, abstract = {INTRODUCTION: Post- or long-COVID-19 conditions manifest with a spectrum of symptoms reminiscent of pulmonary, musculoskeletal, psychological and neurological disorders. Individuals with post- or long-COVID-19 syndrome often present with myalgia, pulmonary problems and fatigue, which significantly impact their daily functioning. Physiotherapy interventions are an accepted medical remedy for these symptoms. This scoping review aims to outline the evidence of physiotherapy interventions documented in the scientific literature, specifically focusing on hands-on therapy.

METHODS AND ANALYSIS: This scoping review conforms to the methodological framework established by the Joanna Briggs Institute (JBI). The procedure for drafting a scoping review involves several steps, starting with defining the research question and the inclusion and exclusion criteria. Eligible studies are those analysing physiotherapy treatment parameters for direct patient interaction in post- and long-COVID-19 patients. Telemedicine and entirely home-based workouts will be excluded aligning with the context of outpatient physiotherapy in Germany. The literature search will be conducted in PubMed, EBSCO research, Scopus, Web of Science, Embase, PEDRO, Cochrane and WISO databases by two independent researchers. Screening, data extraction and a critical appraisal will be performed by these researchers using assessment tools provided by the JBI. Extracted data will encompass demographic characteristics, definitions of post- or long-COVID-19 conditions, descriptions of interventions, their treatment parameters and treatment outcome. Subsequently, findings will be disseminated through a scoping review article or conference presentation.

ETHICS AND DISSEMINATION: Given that this review does not involve human participants, ethical committee approval is deemed unnecessary. The results will be published in peer-reviewed journals and presented at academic and physiotherapeutic conferences.}, } @article {pmid39209348, year = {2024}, author = {Twycross, A and Hughes, B and Hargrave, K}, title = {Building an NHS that truly supports people living with long COVID and ME: government action needed now.}, journal = {Evidence-based nursing}, volume = {27}, number = {4}, pages = {125-126}, doi = {10.1136/ebnurs-2024-104177}, pmid = {39209348}, issn = {1468-9618}, mesh = {Humans ; *COVID-19 ; *State Medicine/organization & administration ; United Kingdom ; *SARS-CoV-2 ; Pandemics ; }, } @article {pmid39209013, year = {2024}, author = {Skare, TL and de Carvalho, JF and de Medeiros, IRT and Shoenfeld, Y}, title = {Ear abnormalities in chronic fatigue syndrome (CFS), fibromyalgia (FM), Coronavirus-19 infectious disease (COVID) and long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/inflammatory syndrome induced by adjuvants (ASIA): A systematic review.}, journal = {Autoimmunity reviews}, volume = {23}, number = {10}, pages = {103606}, doi = {10.1016/j.autrev.2024.103606}, pmid = {39209013}, issn = {1873-0183}, mesh = {Humans ; Autoimmune Diseases/etiology ; *COVID-19/complications/prevention & control ; COVID-19 Vaccines/adverse effects ; *Fatigue Syndrome, Chronic/complications ; *Fibromyalgia/complications ; Post-Acute COVID-19 Syndrome/complications ; *Postural Orthostatic Tachycardia Syndrome/complications ; SARS-CoV-2 ; }, abstract = {Chronic fatigue syndrome (CFS), fibromyalgia (FM), silicone breast implants (SBI), Coronavirus-19 infectious disease (COVID), COVID-19 vaccination (post-COVIDvac-syndrome), Long-COVID syndrome (PCS), sick-building syndrome (SBS), post-orthostatic tachycardia syndrome (PoTS), and autoimmune/ inflammatory syndrome induced by adjuvants (ASIA) are a cluster of poorly understood medical conditions that have in common a group of ill-defined symptoms and dysautonomic features. Most of the clinical findings of this group of diseases are unspecific, such as fatigue, diffuse pain, cognitive impairment, paresthesia, tachycardia, anxiety, and depression. Hearing disturbances and vertigo have also been described in this context, the underlying pathophysiologic process for these conditions might rely on autonomic autoimmune dysbalance. The authors procced a literature review regarding to hearing and labyrinthic disturbances in CSF, FM, SBI, COVID, post-COVIDvac-syndrome, PCS, SBS, POTS, and ASIA. The PRISMA guidelines were followed, and the literature reviewed encompassed papers from January 1990 to January 2024. After the initial evaluation of the articles found in the search through Pubmed, Scielo and Embase, a total of 172 articles were read and included in this review. The prevalence of hearing loss, dizziness, vertigo and tinnitus was described and correlated with the diseases investigated in this study. There are great variability in the frequencies of symptoms found, but cochlear complaints are the most frequent in most studies. Vestibular symptoms are less reported. The main pathophysiological mechanisms are discussed. Direct effects of the virus in the inner ear or nervous pathways, impaired vascular perfusion, cross-reaction or autoimmune immunoreactivity, oxidative stress, DNA methylation, epigenetic modifications and gene activation were implicated in the generation of the investigated symptoms. In clinical practice, all patients with these autoimmune conditions who have any audiological complaint an ENT consultation followed by an audiometry are needed.}, } @article {pmid39208773, year = {2024}, author = {Oh, J and Chung, EJ and Jung, JH and Lee, JS and Oh, SI}, title = {Characteristics and Impact of Long COVID at a Neurology Clinic.}, journal = {European neurology}, volume = {87}, number = {5-6}, pages = {230-241}, pmid = {39208773}, issn = {1421-9913}, mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/complications/psychology ; Retrospective Studies ; Aged ; *Nervous System Diseases/etiology/virology/epidemiology ; Adult ; *Anxiety/etiology ; *Fatigue/etiology ; *Depression/etiology/epidemiology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Republic of Korea/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Neurology ; }, abstract = {INTRODUCTION: Long COVID can also lead to neurological sequelae that affect existing diseases. This study explored how COVID-19 infection affects neurological patients and the relationship between long COVID and exacerbating factors.

METHODS: This retrospective study was conducted on 85 patients with neurological diseases after COVID-19 at the Neurology Department, Inje University Busan Paik Hospital, Korea. The data were collected between August and October 2022. The patients had a medical history, including COVID-19 infection, and completed symptom questionnaires. A long COVID questionnaire consisting of 35 inquiries in 10 categories was completed. Anxiety, depression, fatigue, functional difficulties, QOL, and health status changes were assessed.

RESULTS: The analysis comprised 85 participants (age: 56.4 ± 15.2 years; 63.5% women). Of the categories, neurological symptoms (68.2%) were the most prevalent, followed by systemic symptoms (64.7%) and cardiopulmonary symptoms (56.5%). Anxiety, depression, and fatigue symptoms were reported by 36.5%, 34.1%, and 42.4% of the participants. Subjective neurological deterioration after COVID-19 was reported in 28 participants (28/81, 34.6%). Anxiety, depression, and fatigue were influenced by long COVID symptoms and the subjective deterioration of neurological conditions.

CONCLUSION: This study analyzed the long COVID symptoms in patients with preexisting neurological conditions and their impact on mental health and quality of life. One-third of the participants reported a subjective worsening of their preexisting neurological conditions. This study highlights the need for comprehensive follow-ups and a multidisciplinary approach for patients with neurological conditions and prolonged COVID-19 symptoms.}, } @article {pmid39208357, year = {2024}, author = {Hall, JP and Kurth, NK and McCorkell, L and Goddard, KS}, title = {Long COVID Among People With Preexisting Disabilities.}, journal = {American journal of public health}, volume = {114}, number = {11}, pages = {1261-1264}, pmid = {39208357}, issn = {1541-0048}, mesh = {Humans ; *Disabled Persons/statistics & numerical data ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Male ; Female ; Prevalence ; Middle Aged ; Adult ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; Health Services Accessibility/statistics & numerical data ; SARS-CoV-2 ; }, abstract = {Objectives. To document the prevalence of long COVID among a sample of survey respondents with long-term disabilities that existed before 2020 and to compare the prevalence among this group with that among the general population. Methods. We conducted a cross-sectional, descriptive study using data from the 2022 National Survey on Health and Disability (n = 2262) and comparative data for the general population from the federal Household Pulse Survey (HPS). Results. The prevalence of long COVID was higher among people with preexisting disabilities than in the general population (40.6% vs 18.9%). Conclusions. People with preexisting disabilities experienced and continue to experience increased exposure to COVID-19 and barriers to accessing health care, COVID-19 vaccines, and COVID-19 tests. These barriers, combined with long-standing health disparities in this population, may have contributed to the greater prevalence of long COVID among people with disabilities. Public Health Implications. The needs of people with disabilities must be centered in the response to the COVID-19 pandemic and future pandemics. (Am J Public Health. 2024;114(11):1261-1264. https://doi.org/10.2105/AJPH.2024.307794).}, } @article {pmid39207648, year = {2024}, author = {Gáspár, Z and Szabó, BG and Ceglédi, A and Lakatos, B}, title = {Human herpesvirus reactivation and its potential role in the pathogenesis of post-acute sequelae of SARS-CoV-2 infection.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39207648}, issn = {2509-2723}, abstract = {The emergence of SARS-CoV-2 has precipitated a global pandemic with substantial long-term health implications, including the condition known as post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID. PASC is marked by persistent symptoms such as fatigue, neurological issues, and autonomic dysfunction that persist for months beyond the acute phase of COVID-19. This review examines the potential role of herpesvirus reactivation, specifically Epstein-Barr virus (EBV) and cytomegalovirus (CMV), in the pathogenesis of PASC. Elevated antibody titers and specific T cell responses suggest recent herpesvirus reactivation in some PASC patients, although viremia is not consistently detected. SARS-CoV-2 exhibits endothelial trophism, directly affecting the vascular endothelium and contributing to microvascular pathologies. These pathologies are significant in PASC, where microvascular dysfunction may underlie various chronic symptoms. Similarly, herpesviruses like CMV also exhibit endothelial trophism, which may exacerbate endothelial damage when reactivated. Evidence suggests that EBV and CMV reactivation could indirectly contribute to the immune dysregulation, immunosenescence, and autoimmune responses observed in PASC. Additionally, EBV may play a role in the genesis of neurological symptoms through creating mitochondrial dysfunction, though direct confirmation remains elusive. The reviewed evidence suggests that while herpesviruses may not play a direct role in the pathogenesis of PASC, their potential indirect effects, especially in the context of endothelial involvement, warrant further investigation.}, } @article {pmid39206795, year = {2024}, author = {Jiang, Y and Neal, J and Sompol, P and Yener, G and Arakaki, X and Norris, CM and Farina, FR and Ibanez, A and Lopez, S and Al-Ezzi, A and Kavcic, V and Güntekin, B and Babiloni, C and Hajós, M}, title = {Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {20}, number = {10}, pages = {7296-7319}, pmid = {39206795}, issn = {1552-5279}, support = {I21 RX003173/RX/RRD VA/United States ; P30 AG072946/AG/NIA NIH HHS/United States ; 1220995//ANID/FONDECYT Regular/ ; 1210176//ANID/FONDECYT Regular/ ; P01 AG078116/AG/NIA NIH HHS/United States ; 101071485//Marie Skłodowska-Curie Doctoral Networks/ ; R01AG057234//National Institute of Aging/ ; R01 AG057234/AG/NIA NIH HHS/United States ; P30AG072946//National Institute of Aging/ ; R56 AG063857/AG/NIA NIH HHS/United States ; 5I21RX003173//United States Department of Veterans Affairs/ ; R21 AG046637/AG/NIA NIH HHS/United States ; 1R21AG046637//National Institute of Aging/ ; R01 AG054484/AG/NIA NIH HHS/United States ; P01AG078116//National Institute of Aging/ ; R01AG063857//National Institute of Aging/ ; HAT-07-60437/ALZ/Alzheimer's Association/United States ; R56 AG060608/AG/NIA NIH HHS/United States ; //Tau Consortium/ ; AARF-21-848281/ALZ/Alzheimer's Association/United States ; R56AG060608//National Institute of Aging/ ; R01 AG063857/AG/NIA NIH HHS/United States ; 2010SH7H3F//Italian Ministry of University, Scientific and Technological Research/ ; //MULTI-PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA/ ; ACT210096//ANID/PIA/ANILLOS/ ; SG-20-725707/ALZ/Alzheimer's Association/United States ; 1210195//ANID/FONDECYT Regular/ ; P50 AG005144/AG/NIA NIH HHS/United States ; PNRR-MAD-2022-12376415//Marie Skłodowska-Curie Doctoral Networks/ ; CW2680521//Takeda/ ; 15150012//ANID/FONDAP/ ; H2021-MSCA-DN-2021//HORIZON 2021/ ; R01AG054484//National Institute of Aging/ ; ID22I10029//FONDEF/ ; //United States National Institute of Health/ ; //Global Brain Health Institute/ ; ID20I10152//FONDEF/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Alzheimer Disease/physiopathology ; *Electroencephalography ; *SARS-CoV-2 ; Dementia/physiopathology ; Cognitive Dysfunction/physiopathology/etiology ; Brain/physiopathology ; }, abstract = {Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.}, } @article {pmid39205608, year = {2024}, author = {Lee, K and Park, J and Lee, J and Lee, M and Kim, HJ and Son, Y and Rhee, SY and Smith, L and Rahmati, M and Kang, J and Lee, H and Ha, Y and Yon, DK}, title = {Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {4}, pages = {943-958}, pmid = {39205608}, issn = {2287-285X}, support = {RS-2023-00248157//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; IITP-2024-RS-2024-00438239//Institute for Information & Communications Technology Planning & Evaluation/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Female ; Male ; Middle Aged ; Republic of Korea/epidemiology ; *Gastrointestinal Diseases/epidemiology ; *SARS-CoV-2/isolation & purification ; United Kingdom/epidemiology ; *Liver Diseases/epidemiology/diagnosis ; Adult ; Aged ; Japan/epidemiology ; Cohort Studies ; Biliary Tract Diseases/epidemiology ; }, abstract = {BACKGROUND/AIMS: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities.

METHODS: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls.

RESULTS: The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08-1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09-1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01-1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort.

CONCLUSION: The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.}, } @article {pmid39205240, year = {2024}, author = {McMillan, P and Turner, AJ and Uhal, BD}, title = {Mechanisms of Gut-Related Viral Persistence in Long COVID.}, journal = {Viruses}, volume = {16}, number = {8}, pages = {}, pmid = {39205240}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/virology/immunology ; *SARS-CoV-2/physiology/pathogenicity ; *Post-Acute COVID-19 Syndrome ; Gastrointestinal Microbiome ; Gastrointestinal Tract/virology ; }, abstract = {Long COVID (post-acute sequelae of COVID-19-PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that long-term dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.}, } @article {pmid39205230, year = {2024}, author = {da Silva, R and Vallinoto, ACR and Dos Santos, EJM}, title = {The Silent Syndrome of Long COVID and Gaps in Scientific Knowledge: A Narrative Review.}, journal = {Viruses}, volume = {16}, number = {8}, pages = {}, pmid = {39205230}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2/genetics ; *Post-Acute COVID-19 Syndrome ; Risk Factors ; Prognosis ; }, abstract = {COVID-19 is still a major public health concern, mainly due to the persistence of symptoms or the appearance of new symptoms. To date, more than 200 symptoms of long COVID (LC) have been described. The present review describes and maps its relevant clinical characteristics, pathophysiology, epidemiology, and genetic and nongenetic risk factors. Given the currently available evidence on LC, we demonstrate that there are still gaps and controversies in the diagnosis, pathophysiology, epidemiology, and detection of prognostic and predictive factors, as well as the role of the viral strain and vaccination.}, } @article {pmid39204279, year = {2024}, author = {Jenkins, F and Mapulanga, T and Thapa, G and da Costa, KAS and Temperton, NJ}, title = {Conference Report: LPMHealthcare Emerging Viruses 2023 (EVOX23): Pandemics-Learning from the Past and Present to Prepare for the Future.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39204279}, issn = {2076-0817}, abstract = {The emergence of SARS-CoV-2 has meant that pandemic preparedness has become a major focus of the global scientific community. Gathered in the historic St Edmund Hall college in Oxford, the one-day LPMHealthcare conference on emerging viruses (6 September 2023) sought to review and learn from past pandemics-the current SARS-CoV-2 pandemic and the Mpox outbreak-and then look towards potential future pandemics. This includes an emphasis on monitoring the "traditional" reservoirs of viruses with zoonotic potential, as well as possible new sources of spillover events, e.g., bats, which we are coming into closer contact with due to climate change and the impacts of human activities on habitats. Continued vigilance and investment into creative scientific solutions is required for issues including the long-term physical and psychological effects of COVID-19, i.e., long COVID. The evaluation of current systems, including environmental monitoring, communication (with the public, regulatory authorities, and governments), and training; assessment of the effectiveness of the technologies/assays we have in place currently; and lobbying of the government and the public to work with scientists are all required in order to build trust moving forward. Overall, the SARS-CoV-2 pandemic has shown how many sectors can work together to achieve a global impact in times of crisis.}, } @article {pmid39204242, year = {2024}, author = {Parás-Bravo, P and Fernández-de-Las-Peñas, C and Ferrer-Pargada, D and Izquierdo-Cuervo, S and Fernández-Cacho, LM and Cifrián-Martínez, JM and Druet-Toquero, P and Pellicer-Valero, O and Herrero-Montes, M}, title = {Serological Biomarkers in Individuals with Interstitial Lung Disease after SARS-CoV-2 Infection and Association with Post-COVID-19 Symptoms.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39204242}, issn = {2076-0817}, abstract = {Patients with interstitial lung disease (ILD) represent a vulnerable population against an acute SARS-CoV-2 infection. It has been observed that up to 80% of patients with ILD can develop post-COVID-19 symptomatology one year after. This secondary analysis aimed to, 1, compare serological biomarkers before and after surpassing a SARS-CoV-2 infection in individuals with interstitial lung disease (ILD) and, 2, to compare serological biomarkers between ILD patients who develop and those who do not develop post-COVID-19 symptoms. Seventy-six patients with ILD (40.4% women, age: 69, SD: 10.5 years) who survived a SARS-CoV-2 infection participated. High-resolution computerized tomography (CT) of the lungs, two pulmonary function tests (forced vital capacity (FVC) and diffusion value of carbon monoxide (DLCO)) and fourteen serological biomarkers were collected before and after SARS-CoV-2 infection. Participants were asked for the presence of post-COVID-19 symptomatology a mean of twelve (SD: eight) months after infection. Sixty patients (79%) showed post-COVID-19 symptoms (mean: 3.5, SD 1.1), with fatigue (68.4%), dyspnea (31.5%), and concentration loss (27.6%) being the most prevalent. Creatine phosphokinase (CPK) was the only biomarker showing differences in our study. In fact, CPK levels were higher after the acute SARS-CoV-2 infection (mean difference: 41.0, 95%CI 10.1 to 71.8, p = 0.03) when compared to before the infection. Thus, CPK levels were also higher in ILD patients with post-COVID-19 fatigue (mean difference: 69.7, 95%CI 12.7 to 126.7, p = 0.015) or with post-COVID-19 dyspnea (mean difference: 34.8, 95%CI 5.2 to 64.4, p = 0.025) than those patients without these post-COVID-19 symptoms. No significant changes in CT or functional pulmonary tests were observed after COVID-19 in patients with ILD. In conclusion, patients with ILD exhibited an increase in CPK levels after SARS-CoV-2 infection, albeit no changes in other serological biomarkers were identified. Similarly, the presence of post-COVID-19 fatigue or dyspnea was also associated with higher CPK levels in ILD patients. Studies investigating long COVID mechanisms in vulnerable populations such as ILD are needed.}, } @article {pmid39202695, year = {2024}, author = {Rettew, A and Garrahy, I and Rahimian, S and Brown, R and Sangha, N}, title = {COVID-19 Coagulopathy.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, pmid = {39202695}, issn = {2075-1729}, abstract = {Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite being a primary respiratory illness, it is commonly complicated by systemic involvement of the vasculature leading to arterial and venous thrombosis. In this review, we will focus on the association between COVID-19 and thrombosis. We will highlight the pathophysiology of COVID-19 coagulopathy. The clinical manifestations of COVID-19 vasculopathy will be discussed with a focus on venous and arterial thromboembolic events. COVID-19 vasculopathy and disseminated intravascular coagulation (DIC) are distinguished within, as well as areas of controversy, such as "long COVID". Finally, the current professional guidelines on prevention and treatment of thrombosis associated with SARS-CoV-2 infection will be discussed.}, } @article {pmid39202641, year = {2024}, author = {Cozma, A and Sitar-Tăut, AV and Orășan, OH and Leucuța, DC and Pocol, TC and Sălăgean, O and Crișan, C and Sporiș, ND and Lazar, AL and Mălinescu, TV and Ganea, AM and Vlad, CV and Horvat, M and Lupșe, MS and Briciu, V}, title = {The Impact of Long COVID on the Quality of Life.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {8}, pages = {}, pmid = {39202641}, issn = {1648-9144}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications ; *Quality of Life ; Prospective Studies ; Adult ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Romania/epidemiology ; *SARS-CoV-2 ; Surveys and Questionnaires ; Fatigue/etiology ; Headache/etiology ; Cough/etiology/physiopathology ; }, abstract = {Background and Objectives: The term long COVID refers to patients with a history of confirmed COVID-19 infection, who present symptoms that last for at least 2 months and cannot be explained by another diagnosis. Objectives: The present study aims to determine the most common symptoms of the long COVID syndrome and their impact on the quality of life. Materials and Methods: A prospective observational study was conducted on patients diagnosed with mild and moderate COVID-19 (based on a positive SARS-CoV-2 molecular diagnostic or rapid antigen test and severity form definition) at the Clinical Hospital of Infectious Diseases, Cluj-Napoca, Romania. Clinical examinations with detailed questions about symptoms were performed at the time of the diagnosis of COVID-19 and the six-month follow-up. Two years after COVID-19 infection, patients were invited to complete an online quality-of-life questionnaire regarding long COVID symptoms. Results: A total of 103 patients (35.92% males) with a mean age of 41.56 ± 11.77 were included in this study. Of the total number of patients, 65.04% presented mild forms of COVID-19. Data regarding the vaccination status showed that 83.5% were vaccinated against SARS-CoV-2. The most common symptoms at diagnosis were cough (80.6%), fatigue (80.4%), odynophagia (76.7%), and headaches (67.6%), with female patients being statistically more likely to experience it (p = 0.014). Patients with moderate forms of the disease had higher levels of both systolic (p = 0.008) and diastolic (p = 0.037) blood pressure at diagnosis, but no statistical difference was observed in the 6-month follow-up. The most common symptoms at 2 years (in 29 respondent subjects) were represented by asthenia (51.7%), headache (34.5%), memory disorders (27.6%), abdominal meteorism (27.6%), and arthralgia (27.6%). In terms of cardiovascular symptoms, fluctuating blood pressure values (20.7%), palpitations (17.2%), and increased heart rate values (17.2%) were recorded. Conclusions: If at the time of diagnosis, the most frequent manifestations of the disease were respiratory, together with headache and fatigue, at re-evaluation, asthenia, decreased effort tolerance, and neuropsychiatric symptoms prevailed. Regarding the cardiovascular changes as part of the long COVID clinical picture, some patients developed prehypertension, palpitations, and tachycardia.}, } @article {pmid39201991, year = {2024}, author = {Davenport, TE and Blitshteyn, S and Clague-Baker, N and Davies-Payne, D and Treisman, GJ and Tyson, SF}, title = {Long COVID Is Not a Functional Neurologic Disorder.}, journal = {Journal of personalized medicine}, volume = {14}, number = {8}, pages = {}, pmid = {39201991}, issn = {2075-4426}, abstract = {Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID. The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID. We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.}, } @article {pmid39201907, year = {2024}, author = {Rothensteiner, M and Leeb, F and Götzinger, F and Tebruegge, M and Zacharasiewicz, A}, title = {Long COVID in Children and Adolescents: A Critical Review.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {39201907}, issn = {2227-9067}, abstract = {(1) Background: Data on persisting symptoms after SARS-CoV-2 infection in children and adolescents are conflicting. Due to the absence of a clear pathophysiological correlate and a definitive diagnostic test, the diagnosis of Long COVID currently rests on consensus definitions only. This review aims to summarise the evidence regarding Long COVID in children and adolescents, incorporating the latest studies on this topic. (2) Methods: We designed a comprehensive search strategy to capture all relevant publications using Medline via the PubMed interface, with the initial literature search conducted in April 2023. To be included, publications had to present original data and include >50 participants with Long COVID symptoms aged between 0 and18 years. (3) Results: A total of 51 studies met the inclusion criteria, with most studies originating from Europe (n = 34; 66.7%), followed by the Americas (n = 8; 15.7%) and Asia (n = 7; 13.7%). Various study designs were employed, including retrospective, cross-sectional, prospective, or ambispective approaches. Study sizes varied significantly, with 18/51 studies having fewer than 500 participants. Many studies had methodological limitations: 23/51 (45.1%) studies did not include a control group without prior COVID-19 infection. Additionally, a considerable number of papers (33/51; 64.7%) did not include a clear definition of Long COVID. Other limitations included the lack of PCR- or serology-based confirmation of SARS-CoV-2 infection in the study group. Across different studies, there was high variability in the reported prevalence of Long COVID symptoms, ranging from 0.3% to 66.5%, with the majority of studies included in this review reporting prevalences of approximately 10-30%. Notably, the two studies with the highest prevalences also reported very high prevalences of Long COVID symptoms in the control group. There was a relatively consistent trend for Long COVID prevalence to decline substantially over time. The prevalence of Long COVID appeared to differ across different paediatric age groups, with teenagers being more commonly affected than younger children. Furthermore, data suggest that children and adolescents are less commonly affected by Long COVID compared to adults. In children and adolescents, Long COVID is associated with a very broad range of symptoms and signs affecting almost every organ system, with the respiratory, cardiovascular, and neuropsychiatric systems being most commonly affected. (4) Conclusions: The heterogeneity and limitations of published studies on Long COVID in children and adolescents complicate the interpretation of the existing data. Future studies should be rigorously designed to address unanswered questions regarding this complex disease.}, } @article {pmid39201736, year = {2024}, author = {Ward, C and Schlichtholz, B}, title = {Post-Acute Sequelae and Mitochondrial Aberration in SARS-CoV-2 Infection.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201736}, issn = {1422-0067}, support = {71-01415/0004604//Gdańsk Medical University/ ; }, mesh = {Humans ; *COVID-19/virology/metabolism/pathology ; *Mitochondria/metabolism ; *SARS-CoV-2/metabolism ; *Immunity, Innate ; *Post-Acute COVID-19 Syndrome ; Proteomics/methods ; }, abstract = {This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection, while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to the interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in the sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to the resolution of questions regarding the pathogenesis of PASC.}, } @article {pmid39201353, year = {2024}, author = {Cozma, A and Sitar-Tăuț, AV and Orășan, OH and Briciu, V and Leucuța, D and Sporiș, ND and Lazăr, AL and Mălinescu, TV and Ganea, AM and Sporiș, BM and Vlad, CV and Lupșe, M and Țâru, MG and Procopciuc, LM}, title = {VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201353}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/genetics/virology ; *Vascular Endothelial Growth Factor A/genetics ; Male ; Female ; Middle Aged ; *Polymorphism, Single Nucleotide ; Aged ; SARS-CoV-2/genetics ; Echocardiography ; Atherosclerosis/genetics ; }, abstract = {The COVID-19 pandemic has raised awareness of the virus's long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040-7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624-7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E'ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients.}, } @article {pmid39200898, year = {2024}, author = {Finamore, P and Arena, E and Lupoi, D and Savito, L and Di Nunzio, F and Furbatto, M and Dragonieri, S and Antonelli Incalzi, R and Scarlata, S}, title = {Long COVID Syndrome: A Narrative Review on Burden of Age and Vaccination.}, journal = {Journal of clinical medicine}, volume = {13}, number = {16}, pages = {}, pmid = {39200898}, issn = {2077-0383}, abstract = {Background/Objective: The COVID-19 pandemic has led to the emergence of post-acute COVID-19 syndrome, also known as long COVID, which presents a significant challenge due to its varied symptoms and unpredictable course, particularly in older adults. Similar to COVID-19 infections, factors such as age, pre-existing health conditions, and vaccination status may influence the occurrence and severity of long COVID. The objective is to analyze the role of aging in the context of long COVID and to investigate prevalence rates and vaccination efficacy to improve prevention strategies and treatment in this age group. Methods: Four researchers independently conducted a literature search of the PubMed database to trace studies published between July 2020 and July 2024. Results: Aging influences both the likelihood of developing long COVID and the recovery process, due to age-related physiological changes, immune system alterations, and the presence of comorbidities. Vaccination plays a key role in reducing the risk of long COVID by attenuating the inflammatory responses associated with its symptoms. Conclusions: Despite the protection vaccines offer against severe infection, hospitalization, and post-infection sequelae, vaccine hesitancy remains a major obstacle, worsening the impact of long COVID. Promising treatments for this condition include antivirals although further research is needed.}, } @article {pmid39200834, year = {2024}, author = {Khodanovich, M and Svetlik, M and Kamaeva, D and Usova, A and Kudabaeva, M and Anan'ina, T and Vasserlauf, I and Pashkevich, V and Moshkina, M and Obukhovskaya, V and Kataeva, N and Levina, A and Tumentceva, Y and Vasilieva, S and Schastnyy, E and Naumova, A}, title = {Demyelination in Patients with POST-COVID Depression.}, journal = {Journal of clinical medicine}, volume = {13}, number = {16}, pages = {}, pmid = {39200834}, issn = {2077-0383}, support = {R24 NS104098/NS/NINDS NIH HHS/United States ; 22-15-00481//Russian Science Foundation/ ; }, abstract = {Background: Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression (PCD) using the recently proposed MRI method, macromolecular proton fraction (MPF) mapping. Methods: The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, and 2 severe) at 13.5 ± 10.0 months post-recovery, with matched controls without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n = 38) included participants with neurological COVID-19 complications, excluding clinical depression. Results: Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination, but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of Hamilton scores, PCD presence, and severity. The number of post-COVID symptoms was a significant predictor of PCD presence, while the number of acute symptoms was a significant predictor of PCD severity. Conclusions: This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.}, } @article {pmid39200685, year = {2024}, author = {Schäfer, IC and Krehbiel, J and Adler, W and Borho, A and Herold, R and Greiner, B and Reuner, M and Morawa, E and Erim, Y}, title = {Three-Month Follow-Up of the Post-COVID Syndrome after Admission to a Specialised Post-COVID Centre-A Prospective Study Focusing on Mental Health with Patient Reported Outcome Measures (PROMs).}, journal = {International journal of environmental research and public health}, volume = {21}, number = {8}, pages = {}, pmid = {39200685}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/psychology ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; *Mental Health ; *Post-Acute COVID-19 Syndrome ; *Patient Reported Outcome Measures ; Follow-Up Studies ; Aged ; SARS-CoV-2 ; Depression/epidemiology/etiology ; Surveys and Questionnaires ; Anxiety/epidemiology ; Fatigue/etiology ; }, abstract = {BACKGROUND AND OBJECTIVE: The impairments and duration of PASC (post-acute sequelae of COVID-19) symptoms in mental health have, to date, not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course.

METHODS: The mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID Syndrome Score), depression (Patient Health Questionnaire-9), somatic symptoms (Patient Health Questionnaire-15), anxiety (Generalized Anxiety Disorder-7), fatigue (Fatigue Severity Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional Malaise Screening) was conducted in the home environment.

RESULTS: In total, 80% of patients experienced severe PASC at follow-up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% of patients, respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained at an unchanged high level. The risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre.

CONCLUSIONS: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for the mental health implications of PASC is needed for the planning of health services and disease prevention.}, } @article {pmid39200127, year = {2024}, author = {Fernández-de-Las-Peñas, C and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Franco-Moreno, A and Ryan-Murua, P and Torres-Macho, J and Pellicer-Valero, OJ and Arendt-Nielsen, L and Giordano, R}, title = {Post-COVID-19 Pain Is Not Associated with DNA Methylation Levels of the ACE2 Promoter in COVID-19 Survivors Hospitalized Due to SARS-CoV-2 Infection.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, pmid = {39200127}, issn = {2227-9059}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {One of theories explaining the development of long-lasting symptoms after an acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include changes in the methylation pattern of the host. The current study aimed to investigate whether DNA methylation levels associated with the angiotensin-converting enzyme 2 (ACE2) promoter are different when comparing individuals previously hospitalized due to COVID-19 who then developed long-lasting post-COVID pain with those previously hospitalized due to COVID-19 who did not develop post-COVID-19 pain symptoms. Non-stimulated saliva samples were obtained from a cohort of 279 (mean age: 56.5, SD: 13.0 years old, 51.5% male) COVID-19 survivors who needed hospitalization. Clinical data were collected from hospital medical records. Participants were asked to disclose pain symptoms developed during the first three months after hospital admission due to COVID-19 and persisting at the time of the interview. Methylations of five CpG dinucleotides in the ACE2 promoter were quantified (as percentages). Participants were evaluated up to 17.8 (SD: 5.3) months after hospitalization. Thus, 39.1% of patients exhibited post-COVID-19 pain. Most patients (77.05%) in the cohort developed localized post-COVID-19 pain. Headache and pain in the lower extremity were experienced by 29.4% of the patients. Seven patients received a post-infection diagnosis of fibromyalgia based on the presence of widespread pain characteristics (11.6%) and other associated symptoms. No significant differences in methylation percentages at any CpG location of the ACE2 promoter were identified when comparing individuals with and without post-COVID-19 pain. The current study did not observe differences in methylation levels of the ACE2 promoter depending on the presence or absence of long-lasting post-COVID-19 pain symptoms in individuals who needed hospitalization due to COVID-19 during the first wave of the pandemic.}, } @article {pmid39199522, year = {2024}, author = {Rudroff, T and Rainio, O and Klén, R}, title = {Leveraging Artificial Intelligence to Optimize Transcranial Direct Current Stimulation for Long COVID Management: A Forward-Looking Perspective.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199522}, issn = {2076-3425}, abstract = {Long COVID (Coronavirus disease), affecting millions globally, presents unprecedented challenges to healthcare systems due to its complex, multifaceted nature and the lack of effective treatments. This perspective review explores the potential of artificial intelligence (AI)-guided transcranial direct current stimulation (tDCS) as an innovative approach to address the urgent need for effective Long COVID management. The authors examine how AI could optimize tDCS protocols, enhance clinical trial design, and facilitate personalized treatment for the heterogeneous manifestations of Long COVID. Key areas discussed include AI-driven personalization of tDCS parameters based on individual patient characteristics and real-time symptom fluctuations, the use of machine learning for patient stratification, and the development of more sensitive outcome measures in clinical trials. This perspective addresses ethical considerations surrounding data privacy, algorithmic bias, and equitable access to AI-enhanced treatments. It also explores challenges and opportunities for implementing AI-guided tDCS across diverse healthcare settings globally. Future research directions are outlined, including the need for large-scale validation studies and investigations of long-term efficacy and safety. The authors argue that while AI-guided tDCS shows promise for addressing the complex nature of Long COVID, significant technical, ethical, and practical challenges remain. They emphasize the importance of interdisciplinary collaboration, patient-centered approaches, and a commitment to global health equity in realizing the potential of this technology. This perspective article provides a roadmap for researchers, clinicians, and policymakers involved in developing and implementing AI-guided neuromodulation therapies for Long COVID and potentially other neurological and psychiatric conditions.}, } @article {pmid39199439, year = {2024}, author = {Simonetti, A and Restaino, A and Calderoni, C and De Chiara, E and D'Onofrio, AM and Lioniello, S and Camardese, G and Janiri, D and Tosato, M and Landi, F and Sani, G}, title = {The Interplay between Gender and Duration of Hospitalization Modulates Psychiatric Symptom Severity in Subjects with Long COVID-19.}, journal = {Brain sciences}, volume = {14}, number = {8}, pages = {}, pmid = {39199439}, issn = {2076-3425}, abstract = {Long COVID-19 is characterized by ongoing symptoms or prolonged or long-term complications of SARS-CoV-2 contraction which persist beyond 4 weeks from the initial onset of symptoms. Gender and duration of hospitalization (DH) are key risk factors for developing long COVID-19 syndrome, but their impact and interplay need further study. This research involved 996 long COVID-19 patients, and we compared the levels of general psychopathology, depression, agitated depression, anxiety, and medication use between hospitalized and non-hospitalized males and females. In the hospitalized patients, multivariate regressions assessed the impact of gender, DH, and the interaction of these variables. The females had higher levels of long COVID-19 symptoms, psychotropic drug use, depression, anxiety, and general psychopathology than the males. The non-hospitalized females exhibited more severe agitated depression than the non-hospitalized males. In females, DH was more strongly correlated with the number of psychotropic medications used during long COVID-19. A negative correlation was found between DH and severity of agitated depression in the female patients only. These results highlight that the gender-specific relationship between DH and agitated depression severity should be explored further.}, } @article {pmid39199353, year = {2024}, author = {Yanai, H and Adachi, H and Hakoshima, M and Katsuyama, H and Sako, A}, title = {The Significance of Endothelial Dysfunction in Long COVID-19 for the Possible Future Pandemic of Chronic Kidney Disease and Cardiovascular Disease.}, journal = {Biomolecules}, volume = {14}, number = {8}, pages = {}, pmid = {39199353}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Renal Insufficiency, Chronic/epidemiology/metabolism ; *Endothelium, Vascular/metabolism/physiopathology ; *Cardiovascular Diseases/epidemiology/metabolism/etiology ; *SARS-CoV-2 ; *Angiotensin-Converting Enzyme 2/metabolism ; Male ; Female ; Biomarkers/metabolism ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Pandemics ; }, abstract = {Various symptoms have been reported to persist beyond the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred to as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 are largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction is a strong candidate explaining the induction of long COVID-19. The angiotensin-converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for atherosclerotic cardiovascular disease (ASCVD) and a history of ASCVD raise the risk of severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with the development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in the development of ASCVD. We consider the influence of long COVID-19 on the development of chronic kidney disease (CKD) and ASCVD. Future assessments of the outcomes of long COVID-19 in patients resulting from therapeutic interventions that improve endothelial function may imply the significance of endothelial dysfunction in the development of long COVID-19.}, } @article {pmid39198643, year = {2024}, author = {Ryu, JK and Yan, Z and Montano, M and Sozmen, EG and Dixit, K and Suryawanshi, RK and Matsui, Y and Helmy, E and Kaushal, P and Makanani, SK and Deerinck, TJ and Meyer-Franke, A and Rios Coronado, PE and Trevino, TN and Shin, MG and Tognatta, R and Liu, Y and Schuck, R and Le, L and Miyajima, H and Mendiola, AS and Arun, N and Guo, B and Taha, TY and Agrawal, A and MacDonald, E and Aries, O and Yan, A and Weaver, O and Petersen, MA and Meza Acevedo, R and Alzamora, MDPS and Thomas, R and Traglia, M and Kouznetsova, VL and Tsigelny, IF and Pico, AR and Red-Horse, K and Ellisman, MH and Krogan, NJ and Bouhaddou, M and Ott, M and Greene, WC and Akassoglou, K}, title = {Fibrin drives thromboinflammation and neuropathology in COVID-19.}, journal = {Nature}, volume = {633}, number = {8031}, pages = {905-913}, pmid = {39198643}, issn = {1476-4687}, support = {K99 AI163868/AI/NIAID NIH HHS/United States ; T32 AI007334/AI/NIAID NIH HHS/United States ; RF1 AG064926/AG/NIA NIH HHS/United States ; R01 HL128503/HL/NHLBI NIH HHS/United States ; S10 RR028962/RR/NCRR NIH HHS/United States ; R01 GM138780/GM/NIGMS NIH HHS/United States ; T32 HL094274/HL/NHLBI NIH HHS/United States ; U24 NS120055/NS/NINDS NIH HHS/United States ; K99 NS126707/NS/NINDS NIH HHS/United States ; R00 NS126707/NS/NINDS NIH HHS/United States ; U19 AI135990/AI/NIAID NIH HHS/United States ; R35 NS097976/NS/NINDS NIH HHS/United States ; R24 GM137200/GM/NIGMS NIH HHS/United States ; S10 OD021784/OD/NIH HHS/United States ; }, mesh = {Mental Fatigue ; Male ; *COVID-19/immunology/pathology/virology/complications ; Neuroinflammatory Diseases/complications/immunology/pathology/virology ; Antibodies, Monoclonal/immunology/pharmacology ; Immunity, Innate ; Spike Glycoprotein, Coronavirus/metabolism ; Macrophage Activation/drug effects ; *Fibrin/antagonists & inhibitors/metabolism ; Fibrinogen/metabolism ; *Inflammation/complications/immunology/pathology/virology ; Oxidative Stress ; Animals ; *Brain/drug effects/immunology/pathology/virology ; Microglia/immunology/pathology ; Female ; Humans ; Killer Cells, Natural/immunology ; Post-Acute COVID-19 Syndrome/immunology/virology ; *Thrombosis/complications/immunology/pathology/virology ; Mice ; Lung/drug effects/immunology/pathology/virology ; SARS-CoV-2/immunology/pathogenicity ; Neurons/pathology/virology ; }, abstract = {Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection[1-4]. Despite the clinical evidence[1,5-7], the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits[1,5,8-10]. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.}, } @article {pmid39197231, year = {2024}, author = {Salzmann, S and Herrmann, M and Henning, M and Schwertner, L and Euteneuer, F and Goldau, L and Bahr, C and Berwanger, C and Rief, W}, title = {Side-effect expectations are associated with disability, physical fitness, and somatic symptoms 3 months after post-COVID neurological inpatient rehabilitation.}, journal = {Journal of psychosomatic research}, volume = {186}, number = {}, pages = {111902}, doi = {10.1016/j.jpsychores.2024.111902}, pmid = {39197231}, issn = {1879-1360}, mesh = {Humans ; Male ; *COVID-19/psychology/rehabilitation ; Female ; Middle Aged ; *Neurological Rehabilitation/methods ; *Physical Fitness ; Fatigue/psychology/etiology ; Adult ; SARS-CoV-2 ; Aged ; Depression/psychology/etiology ; Inpatients/psychology ; Medically Unexplained Symptoms ; Anxiety/psychology/etiology ; Cohort Studies ; Disabled Persons/psychology/rehabilitation ; }, abstract = {INTRODUCTION: The COVID-19 pandemic, caused by SARS-CoV-2, has led to long-term health issues known as post-COVID-19 condition, including fatigue and cognitive disruptions. Despite its recognition as a public health concern, the efficacy of therapeutic interventions, especially in neurological rehabilitation, remains unclear. This study examines how treatment expectations are associated with psychological and physical outcomes in post-COVID-19 condition neurological rehabilitation.

METHODS: In an observational cohort study 61 patients with confirmed post-COVID-19 condition were included. Baseline (T0) data on treatment and side effect expectations were collected, before participants underwent a 4-6 week multidisciplinary rehabilitation program. Primary outcome was illness-related disability (Pain Disability Index). Secondary outcomes included depressive symptoms (PHQ-9), anxiety levels (GAD-7), functional status (PCFS), fatigue (CFS), and physical fitness (6MWT). Regression models analyzed the associations of baseline expectations with outcomes at the end of rehabilitation (T1) and three months post-rehabilitation (T2).

RESULTS: After adjusting for multiple testing, higher baseline side-effect expectations were associated with greater illness-related disability (β = 0.42, p = 0.007), reduced physical fitness (β = - 0.24, p = 0.04), and more somatic symptoms (β = 0.33, p = 0.006) at follow-up (T2). Positive treatment expectations were associated with poorer functional status (β = 0.35, p = 0.011) at T2.

CONCLUSION: This study highlights the associations of side-effect expectations with post-COVID-19 condition rehabilitation outcomes. Higher side-effect expectations were associated to poorer outcomes, indicating a nocebo effect. Surprisingly, positive expectations were linked to worse outcomes, possibly due to unrealistic optimism. Managing patient expectations realistically and addressing side-effect concerns seems crucial for optimizing rehabilitation outcomes.}, } @article {pmid39197160, year = {2024}, author = {Tacchini-Jacquier, N and Monnay, S and Coquoz, N and Bonvin, E and Verloo, H}, title = {Patient-Reported Experiences of Persistent Post-COVID-19 Conditions After Hospital Discharge During the Second and Third Waves of the Pandemic in Switzerland: Cross-Sectional Questionnaire Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e47465}, pmid = {39197160}, issn = {2369-2960}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; *Patient Discharge/statistics & numerical data ; Adult ; Aged ; Surveys and Questionnaires ; Switzerland/epidemiology ; *Self Report ; Pandemics ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND: Hospitalized patients infected with SARS-CoV-2 should recover within a few weeks. However, even those with mild versions can experience symptoms lasting 4 weeks or longer. These post-COVID-19 condition (PCC) comprise various new, returning, or ongoing symptoms that can last for months or years and cause disability. Few studies have investigated PCC using self-reports from discharged patients infected with SARS-CoV-2 to complement clinical and biomarker studies.

OBJECTIVE: This study aimed to investigate self-reported, persistent PCC among patients infected with SARS-CoV-2 who were discharged during the second and third waves of the COVID-19 pandemic.

METHODS: We designed, pretested, and posted an ad hoc paper questionnaire to all eligible inpatients discharged between October 2020 and April 2021. At 4 months post discharge, we collected data on PCC and scores for the Multidimensional Fatigue Inventory (MFI), the Patient Health Questionnaire-4 (PHQ-4), a Brief Memory Screening Scale (Q3PC), and a posttraumatic stress disorder scale (PCL-5). Descriptive, inferential, and multivariate linear regression statistics assessed PCC symptomatology, associations, and differences regarding sociodemographic characteristics and hospital length of stay (LOS). We examined whether our variables of interest significantly predicted MFI scores.

RESULTS: Of the 1993 valid questionnaires returned, 245 were from discharged patients with SARS-CoV-2 (median age 71, IQR 62.7-77 years). Only 28.2% (69/245) of respondents were symptom-free after 4 months. Women had significantly more persistent PCC symptoms than men (P≤.001). Patients with a hospital LOS ≥11 days had more PCC symptoms as well (P<.001)-women had more symptoms and longer LOS. No significant differences were found between age groups (18-64, 65-74, and ≥75 years old; P=.50) or between intensive care units and other hospitalization units (P=.09). Patients self-reported significantly higher PHQ-4 scores during their hospitalization than at 4 months later (P<.001). Three-fourth (187/245, 76.4%) of the respondents reported memory loss and concentration disorders (Q3PC). No significant differences in the median MFI score (56, IQR 1-3, range 50-60]) were associated with sociodemographic variables. Patients with a hospital LOS of ≥11 days had a significantly higher median PCL-5 score (P<.001). Multivariate linear regression allowed us to calculate that the combination of PHQ-4, Q3PC, and PCL-5 scores, adjusted for age, sex, and LOS (of either ≥11 days [median 2 symptoms, IQR 1-5] or <11 days), did not significantly predict MFI scores (R[2]=0.09; F4,7 =1.5; P=.22; adjusted R[2]=0.06).

CONCLUSIONS: The majority of inpatients infected with SARS-CoV-2 presented with PCC 4 months after discharge, with complex clinical pictures. Only one-third of them were symptom-free during that time. Based on our findings, MFI scores were not directly related to self-reported depression, anxiety, or posttraumatic scores adjusted for age, sex, or LOS. Further research is needed to explore PCC and fatigue based on self-reported health experiences of discharged inpatients infected with SARS-CoV-2.}, } @article {pmid39197062, year = {2024}, author = {Al Masoodi, WTM and Radhi, SW and Al-Hakeim, HK and Abdalsada, HK}, title = {Electrolytes as predictors of fibro fatigue scores in Long-COVID patients.}, journal = {PloS one}, volume = {19}, number = {8}, pages = {e0309348}, pmid = {39197062}, issn = {1932-6203}, mesh = {Humans ; Female ; *COVID-19/blood/complications/diagnosis ; Male ; Middle Aged ; *Electrolytes/blood ; *C-Reactive Protein/analysis/metabolism ; *Biomarkers/blood ; *Fatigue/blood ; Adult ; Calcium/blood/metabolism ; SARS-CoV-2/isolation & purification ; Aged ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; Magnesium/blood/analysis ; Case-Control Studies ; ROC Curve ; }, abstract = {BACKGROUND: The complex effects of Long-COVID, a syndrome marked by enduring symptoms after COVID-19 infection, with an emphasis on patients' differing degrees of fibro fatigue (FF). Electrolyte disturbances may affect the severity of FF and may be used as a predictive tool for severe FF in Long-COVID patients.

OBJECTIVE: The aim is to use the electrolyte levels for prediction of the Long-COVID patients with high FF levels.

METHODS: The electrolyte levels, calcium, and magnesium, as well as albumin and C-reactive protein levels were measured in 120 Long-COVID patients and 60 controls. FF scale was used for scoring the fatigue severity in all subjects. Patients were divided into high-FF (FF score>25) and moderate-FF group (FF score<25).

RESULTS: FF is the major effector on the serum biomarker levels. High-FF group had older people, longer disease durations, lower SpO2, higher CRP, and higher peak temperatures than the control group. High-FF group has a significant decrease in serum total and ionized calcium compared with the controls and low-FF group. After controlling the cofounders, the major factor controlling the levels of the measured biomarkers is the FF value (Partial η2 = 0.468). The ROC-AUC analysis showed that the peak body temperature, Low-SpO2, high-CRP, and low electrolytes can predict the high-FF in a patient with Long-COVID with a moderate sensitivity and specificities (61.6-70%).

CONCLUSION: Long-COVID patients have an elevation in FF score. The decline in electrolytes can predict the severity of FF with moderate sensitivities and specificities.}, } @article {pmid39196964, year = {2024}, author = {Gross, RS and Thaweethai, T and Kleinman, LC and Snowden, JN and Rosenzweig, EB and Milner, JD and Tantisira, KG and Rhee, KE and Jernigan, TL and Kinser, PA and Salisbury, AL and Warburton, D and Mohandas, S and Wood, JC and Newburger, JW and Truong, DT and Flaherman, VJ and Metz, TD and Karlson, EW and Chibnik, LB and Pant, DB and Krishnamoorthy, A and Gallagher, R and Lamendola-Essel, MF and Hasson, DC and Katz, SD and Yin, S and Dreyer, BP and Carmilani, M and Coombs, K and Fitzgerald, ML and Güthe, N and Hornig, M and Letts, RJ and Peddie, AK and Taylor, BD and Balaraman, V and Bogie, A and Bukulmez, H and Dozor, AJ and Eckrich, D and Elliott, AJ and Evans, DN and Farkas, JS and Faustino, EVS and Fischer, L and Gaur, S and Harahsheh, AS and Hasan, UN and Hsia, DS and Huerta-Montañez, G and Hummel, KD and Kadish, MP and Kaelber, DC and Krishnan, S and Kosut, JS and Larrabee, J and Lim, PPC and Michelow, IC and Oliveira, CR and Raissy, H and Rosario-Pabon, Z and Ross, JL and Sato, AI and Stevenson, MD and Talavera-Barber, MM and Teufel, RJ and Weakley, KE and Zimmerman, E and Bind, MC and Chan, J and Guan, Z and Morse, RE and Reeder, HT and Akshoomoff, N and Aschner, JL and Bhattacharjee, R and Cottrell, LA and Cowan, K and D'Sa, VA and Fiks, AG and Gennaro, ML and Irby, K and Khare, M and Guttierrez, JL and McCulloh, RJ and Narang, S and Ness-Cochinwala, M and Nolan, S and Palumbo, P and Ryu, J and Salazar, JC and Selvarangan, R and Stein, CR and Werzberger, A and Zempsky, WT and Aupperle, R and Baker, FC and Banich, MT and Barch, DM and Baskin-Sommers, A and Bjork, JM and Bookheimer, SY and Brown, SA and Casey, BJ and Chang, L and Clark, DB and Dale, AM and Dapretto, M and Ernst, TM and Fair, DA and Feldstein Ewing, SW and Foxe, JJ and Freedman, EG and Friedman, NP and Garavan, H and Gee, DG and Gonzalez, R and Gray, KM and Heitzeg, MM and Herting, MM and Jacobus, J and Laird, AR and Larson, CL and Lisdahl, KM and Luciana, M and Luna, B and Madden, PAF and McGlade, EC and Müller-Oehring, EM and Nagel, BJ and Neale, MC and Paulus, MP and Potter, AS and Renshaw, PF and Sowell, ER and Squeglia, LM and Tapert, S and Uddin, LQ and Wilson, S and Yurgelun-Todd, DA and Foulkes, AS and Stockwell, MS and , and , }, title = {Characterizing Long COVID in Children and Adolescents.}, journal = {JAMA}, volume = {332}, number = {14}, pages = {1174-1188}, pmid = {39196964}, issn = {1538-3598}, abstract = {IMPORTANCE: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

OBJECTIVE: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: PASC and 89 prolonged symptoms across 9 symptom domains.

RESULTS: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

CONCLUSIONS AND RELEVANCE: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.}, } @article {pmid39196796, year = {2024}, author = {Zalaquett, N and Lutchman, K and Iliaki, E and Buley, J and Nathan, N and Sotos Prieto, M and Kales, SN and Lan, FY}, title = {Findings Associated With Prolonged COVID-19 Recovery Among Boston Healthcare Workers.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {12}, pages = {962-969}, doi = {10.1097/JOM.0000000000003221}, pmid = {39196796}, issn = {1536-5948}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Cross-Sectional Studies ; *Health Personnel/psychology/statistics & numerical data ; Female ; Adult ; Middle Aged ; Boston/epidemiology ; *SARS-CoV-2 ; Surveys and Questionnaires ; *Quality of Life ; Anxiety/epidemiology ; Depression/epidemiology ; Time Factors ; }, abstract = {OBJECTIVE: This study aimed to evaluate the long-term, symptomatic recovery of healthcare workers from acute COVID-19 infections up to 3 years after the initial COVID-19 outbreak.

METHODS: A cross-sectional study was performed among employees of a community-based healthcare system in Massachusetts who had a recorded positive COVID-19 test. Survey responses were collected between September 2022 and January 2023. The survey included validated questionnaires: WHOQOL-BREF, EQ-5D-5 L, DASS-21, FCV-19S, K6+, and the Insomnia Severity Index. We compared the long-COVID (ie, symptoms lasting >28 days) and non-long-COVID groups.

RESULTS: Among the 280 respondents (15.2% response rate), those with long COVID (73.4%) reported significantly worse quality of life and greater levels of depression, anxiety, and stress metrics. However, no significant difference was found between the two groups' fear of COVID-19.

CONCLUSIONS: Targeted support for healthcare workers with prolonged symptoms after COVID-19 is warranted.}, } @article {pmid39196199, year = {2024}, author = {Forte, E}, title = {Abnormal complement activation is a sign of long COVID.}, journal = {Nature cardiovascular research}, volume = {3}, number = {2}, pages = {95}, doi = {10.1038/s44161-024-00434-y}, pmid = {39196199}, issn = {2731-0590}, } @article {pmid39195858, year = {2024}, author = {Tsai, DH and Harmon, E and Goelen, J and Barry, HE and Chen, LY and Hsia, Y}, title = {Evaluating the Risk-Benefit Profile of Corticosteroid Therapy for COVID-19 Patients: A Scoping Review.}, journal = {Pharmacy (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {39195858}, issn = {2226-4787}, abstract = {BACKGROUND: The 2019 coronavirus (COVID-19) outbreak was declared a global pandemic in March 2020. It quickly spread across all continents, causing significant social, environmental, health, and economic impacts. During the pandemic, there has been consideration of repurposing and repositioning of medications, such as corticosteroids, for the treatment of hospitalised COVID-19 patients.

OBJECTIVE: To assess and summarise corticosteroid regimens used for hospitalised COVID-19 patients, focusing on dosage, route of administration, and clinical outcome from clinical trials.

METHODS: PubMed and Embase databases and the grey literature were searched to identify randomised controlled trials (RCTs) that evaluated the efficacy of corticosteroids in hospitalised patients with COVID-19 between January 2020 and January 2023. This scoping review was conducted in line with the PRISMA extension for scoping reviews (PRISMA-ScR) checklist.

KEY FINDINGS: A total of 24 RCTs were eligible for inclusion. There was variation in the steroid regimens used for treatment across COVID-19 trials. Despite the heterogeneity of included RCTs, the overall results have shown the benefits of improving lung function and a lower all-cause mortality rate in hospitalised COVID-19 patients treated with systematic corticosteroids.

CONCLUSIONS: Corticosteroids have proven to be an effective treatment for COVID-19 patients in critical condition. However, comparative effectiveness studies should be conducted to assess the efficacy and safety of optimal corticosteroid treatment at the population level. Moreover, the global burden of long COVID is significant, affecting millions with persistent symptoms and long-term health complications. Thus, it is also necessary to evaluate the optimal steroid regimen for long COVID treatment.}, } @article {pmid39195566, year = {2024}, author = {Almeria, M and Cejudo, JC and Deus, J and Krupinski, J}, title = {Long Neurocognitive and Neuropsychiatric Sequelae in Participants with Post-COVID-19 Infection: A Longitudinal Study.}, journal = {Neurology international}, volume = {16}, number = {4}, pages = {853-868}, pmid = {39195566}, issn = {2035-8385}, abstract = {OBJECTIVE: To evaluate and characterize the cognitive changes in COVID-19 participants at 6-month follow-up, and to explore a possible association with clinical symptoms, emotional disturbance and disease severity.

METHODS: This single-center longitudinal cohort study included participants aged 20 and 60 years old to exclude cognitive impairment age-associated with confirmed COVID-19 infection. The initial evaluation occurred 10 to 30 days after hospital or ambulatory discharge, with a subsequent follow-up at 6 months. Patients who had a history of cognitive impairment, neurological conditions, or serious psychiatric disorders were not included. Information on demographics and laboratory results was gathered from medical records. Cognitive outcomes were assessed with a neuropsychological battery including attention, verbal and visual memory, language and executive function tests.

RESULTS: A total of 200 participants were included in the study, and 108 completed the follow-up visit. At the 6-month follow-up, comparing the means from baseline with those of the follow-up evaluation, significant overall improvement was observed in verbal and visual memory subtests (p = 0.001), processing speed (p = 0.001), executive function (p = 0.028; p = 0.016) and naming (p = 0.001), independently of disease severity and cognitive complaints. Anxiety and depression were significantly higher in groups with Subjective Cognitive Complaints (SCC) compared to those without (p < 0.01 for both).

CONCLUSIONS: Persistent symptoms are common regardless of disease severity and are often linked to cognitive complaints. Six months after COVID-19, the most frequently reported symptoms included headache, dyspnea, fatigue, cognitive complaints, anxiety, and depression. No cognitive impairment was found to be associated with the severity of COVID-19. Overall, neuropsychological and psychopathological improvement was observed at 6 months regardless of disease severity and cognitive complaints.}, } @article {pmid39192882, year = {2024}, author = {Hurtado, C and Rojas-Gualdrón, DF and Pérez Giraldo, GS and Villegas Arbelaez, E and Mantilla, SEM and Campuzano-Sierra, M and Ospina-Patino, S and Arroyave-Bustamante, M and Uribe-Vizcarra, V and Restrepo-Arbelaez, D and Cardona, P and Llano-Piedrahita, J and Vásquez-Builes, S and Agudelo-Quintero, E and Vélez-Arroyave, J and Menges, S and Jimenez, M and Miller, J and Quique, YM and Koralnik, IJ}, title = {Neurologic manifestations of Long COVID in Colombia: a comparative analysis of post-hospitalization vs. non-hospitalized patients.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1450110}, pmid = {39192882}, issn = {1662-5161}, abstract = {OBJECTIVE: To analyze patient-reported outcomes, cognitive function, and persistent symptoms in patients with neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) in Colombia.

METHODS: We recruited patients with laboratory-confirmed COVID-19 and PASC symptoms lasting more than 6 weeks at the CES University and CES Clinic (Medellín, Colombia). We included 50 post-hospitalization Neuro-PASC (PNP) and 50 non-hospitalized Neuro-PASC (NNP) patients. Long-COVID symptoms, cognitive (NIH Toolbox v2.1-Spanish for 18+), patient-reported (PROMIS) outcomes, and relevant medical history were evaluated. Statistical analyses were performed via generalized linear models.

RESULTS: Overall, brain fog (60%), myalgia (42%), and numbness or tingling (41%) were the most common neurological symptoms, while fatigue (74%), sleep problems (46%), and anxiety (44%) were the most common non-neurological symptoms. Compared to NNP, PNP patients showed a higher frequency of abnormal neurological exam findings (64% vs. 42%, p = 0.028). Both groups had impaired quality of life (QoL) in domains of cognition, fatigue, anxiety depression and sleep disturbance, and performed worse on processing speed and attention than a normative population. In addition, NNP patients performed worse on executive function than PNP patients (T-score 42.6 vs. 48.5, p = 0.012). PASC symptoms of anxiety and depression were associated with worse QoL and cognitive outcomes. Brain fog and fatigue remained persistent symptoms across all durations of Long COVID.

CONCLUSION: Our findings highlight the high incidence and heterogeneity of the neurologic symptoms and impacts of Long COVID even more than 2 years from disease onset. Early detection, emotional support and targeted management of Neuro-PASC patients are warranted.}, } @article {pmid39192351, year = {2024}, author = {Xavier, DM and Abreu, RAL and Corrêa, FG and Silva, WT and Silva, SN and Galvão, EL and Junior, MGDN}, title = {Effects of respiratory muscular training in post-covid-19 patients: a systematic review and meta-analysis of randomized controlled trials.}, journal = {BMC sports science, medicine & rehabilitation}, volume = {16}, number = {1}, pages = {181}, pmid = {39192351}, issn = {2052-1847}, abstract = {BACKGROUND: Post-Covid-19 syndrome is defined as non-self-sustaining signs and/or symptoms lasting more than 12 weeks, occurring during or after a Covid-19 infection. The primary outcome was the analysis of the respiratory muscle training (RMT) result in respiratory muscle strength, (maximum inspiratory pressure (MIP) e maximum expiratory pressure (MEP)); and the secondary results were the analysis of lung function, dyspnea, quality of life (QoL), fatigue and functional performance.

METHODS: The PICO description for this research was: P: patients diagnosed with post-Covid-19; I: RMT; C: Sham or simulated inspiratory or expiratory muscle training and usual care; O: MIP, MEP, Lung Function, level of dyspnea, QoL and functional performance. On January 15, 2024, the following databases were consulted: PubMed, Lilacs, Cochrane Library, PEDro and EMBASE. Randomized clinical trials were included without restrictions on year of publication or language. The data selection and extraction steps were carried out by two independent reviewers.

RESULTS: The search in the databases resulted in a total of 14,216 studies, and after the eligibility process, 7 studies were included with a sample of 527 patients. The MIP results suffered a statistically significant increase, that is, the RMT was favorable to improve the MIP (MD = 29.55cmH2O IC 95%: 7.56cmH2O to 51.54cmH2O, p = 0,00001). For the MEP outcome, the results were statistically significant in favor of RMT (MD = 10.93cmH2O CI 95%: 3.65cmH2O to 18.21cmH2O, p = 0.00001). We also noticed a significant improvement for the group that received the RMT in the distance covered in the 6-Minute Walk Test (6MWT) MD = 40.70 m CI 95%: 18.23 m to 65.17 m%, p = 0.01).

CONCLUSION: We noticed that RMT is being used in patients with respiratory diseases, including post-Covid-19. Our systematic review observed that this training provides an increase in inspiratory and expiratory muscle strength, a reduction in dyspnea levels, and an increase in the distance covered in the 6MWT and improved QoL in post-covid patients after intervention.}, } @article {pmid39191462, year = {2024}, author = {Gardner, E and Lockrey, A and Stoesser, KL and Leiser, JP and Brown, J and Kiraly, B and Ose, DJ}, title = {Challenges in Receiving Care for Long COVID: A Qualitative Interview Study Among Primary Care Patients About Expectations and Experiences.}, journal = {Annals of family medicine}, volume = {22}, number = {5}, pages = {369-374}, pmid = {39191462}, issn = {1544-1717}, mesh = {Humans ; Female ; Male ; *Primary Health Care ; Middle Aged ; *COVID-19/psychology/therapy ; *Qualitative Research ; Adult ; Aged ; SARS-CoV-2 ; Interviews as Topic ; Post-Acute COVID-19 Syndrome ; Physician-Patient Relations ; }, abstract = {BACKGROUND: For many patients with post-COVID-19 condition (long COVID), primary care is the first point of interaction with the health care system. In principle, primary care is well situated to manage long COVID. Beyond expressions of disempowerment, however, the patient's perspective regarding the quality of long COVID care is lacking. Therefore, this study aimed to analyze the expectations and experiences of primary care patients seeking treatment for long COVID.

METHODS: A phenomenological approach guided this analysis. Using purposive sampling, we conducted semistructured interviews with English-speaking, adult primary care patients describing symptoms of long COVID. We deidentified and transcribed the recorded interviews. Transcripts were analyzed using inductive qualitative content analysis.

RESULTS: This article reports results from 19 interviews (53% female, mean age = 54 years). Patients expected their primary care practitioners (PCPs) to be knowledgeable about long COVID, attentive to their individual condition, and to engage in collaborative processes for treatment. Patients described 2 areas of experiences. First, interactions with clinicians were perceived as positive when clinicians were honest and validating, and negative when patients felt dismissed or discouraged. Second, patients described challenges navigating the fragmented US health care system when coordinating care, treatment and testing, and payment.

CONCLUSION: Primary care patients' experiences seeking care for long COVID are incongruent with their expectations. Patients must overcome barriers at each level of the health care system and are frustrated by the constant challenges. PCPs and other health care professionals might increase congruence with expectations and experiences through listening, validating, and advocating for patients with long COVID.Annals Early Access article.}, } @article {pmid39191351, year = {2025}, author = {Vyas, CM and Wang, S and Menor, AM and Kubzansky, LD and Slopen, N and Rich-Edwards, J and Chavarro, JE and Kang, JH and Roberts, AL}, title = {Association between childhood abuse and risk of post-COVID-19 conditions: Results from three large prospective cohort studies.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {143-150}, pmid = {39191351}, issn = {1090-2139}, support = {R01 HD057368/HD/NICHD NIH HHS/United States ; U01 HL145386/HL/NHLBI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; R24 ES028521/ES/NIEHS NIH HHS/United States ; R01 HD094725/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Prospective Studies ; Adult ; Male ; Middle Aged ; Risk Factors ; *SARS-CoV-2 ; Child ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Adult Survivors of Child Abuse/psychology ; Child Abuse/psychology ; Aged ; Cohort Studies ; Life Style ; Child Abuse, Sexual/psychology ; Anxiety/epidemiology/psychology ; Asthma/epidemiology/psychology ; }, abstract = {BACKGROUND: Significant early life adversities, such as childhood sexual and physical/emotional abuse, are associated with risk of poor health outcomes but are understudied risk factors for post-COVID-19 conditions. In this prospective study, we examined the associations between combined exposure to sexual and physical/emotional abuse during childhood with risk of post-COVID-19 conditions in adulthood. Additionally, we explored the extent to which lifestyle, health-related and psychological factors explain this association.

METHODS: We used data from three large, ongoing cohorts: Nurses' Health Study (NHS)-II, NHS3, and the Growing Up Today Study. Between April 2020 and November 2021, participants responded to periodic COVID-19 surveys. Participants were included if they responded to a questionnaire about childhood abuse, subsequently tested positive for SARS-CoV-2 infection and responded to questions about post-COVID-19 conditions. Childhood sexual abuse was measured before the COVID-19 pandemic with the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale, and physical/emotional abuse was measured with the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire. Post-COVID-19 conditions, defined as COVID-19-related symptoms lasting 4 weeks or longer (e.g., fatigue, dyspnea), were self-reported in the final COVID-19 questionnaire in November 2021. Sexual abuse and physical/emotional abuse were examined separately and jointly in relation to post-COVID-19 conditions. Data on key lifestyle (e.g., cigarette smoking), health-related (e.g., asthma, diabetes), and psychological factors (e.g., depression and anxiety) were obtained.

RESULTS: Of 2851 participants, the mean age (range) was 55.8 (22.0-75.0) years; 2789 (97.8 %) were females, and 2750 (96.5 %) were whites. We observed a dose-dependent relationship between severity of childhood abuse and post-COVID conditions (p-trend:<0.0001); participants with severe versus no childhood abuse had a 42 % higher subsequent risk of post-COVID conditions [relative risk (95 % confidence interval): 1.42 (1.25 to 1.61)]. Key lifestyle, health-related, and psychological factors mediated 25.5 % of this association. Both sexual and physical/emotional abuse, were independently associated with post-COVID conditions.

CONCLUSIONS: In this prospective study of 2851 participants, childhood abuse was significantly associated with increased risk of post-COVID conditions. Biological pathways connecting childhood abuse with subsequent risk of post-COVID conditions should be investigated.}, } @article {pmid39190040, year = {2024}, author = {Kwan, ATH and Lakhani, M and Le, GH and Singh, G and Teopiz, KM and Ceban, F and Nijjar, CS and Meshkat, S and Badulescu, S and Ho, R and Rhee, TG and Di Vincenzo, JD and Gill, H and McIntyre, RS}, title = {Subjective and objective measures of cognitive function are correlated in persons with Post-COVID-19 Condition: a secondary analysis of a Randomized Controlled Trial.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1959-1966}, pmid = {39190040}, issn = {1433-8491}, support = {H. Lundbeck A/S//H. Lundbeck A/S/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cognition/physiology ; Cognitive Dysfunction/etiology/physiopathology ; *COVID-19/complications ; Double-Blind Method ; *Neuropsychological Tests ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications.

METHODS: This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively.

RESULTS: A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version, NcombinedDSST), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (β = -0.003, p = 0.002) and TMT-B (β = 0.003, p = 0.008) scores, but not with TMT-A scores (β = -0.001, p = 0.751).

CONCLUSIONS: Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.}, } @article {pmid39189651, year = {2024}, author = {Thierry, AR and Salmon, D}, title = {Inflammation-, immunothrombosis,- and autoimmune-feedback loops may lead to persistent neutrophil self-stimulation in long COVID.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29887}, doi = {10.1002/jmv.29887}, pmid = {39189651}, issn = {1096-9071}, support = {//SIRIC Montpellier Cancer/ ; //Société Française des Acides Nucléiques Circulants/ ; //INSERM/ ; }, mesh = {*Inflammation/immunology ; *Thromboinflammation/immunology ; *Autoimmunity ; *Feedback, Physiological ; *Neutrophils/immunology ; *Post-Acute COVID-19 Syndrome/immunology/physiopathology ; Extracellular Traps/immunology ; Communicable Diseases/pathology ; }, abstract = {Understanding the pathophysiology of long COVID is one of the most intriguing challenges confronting contemporary medicine. Despite observations recently made in the relevant molecular, cellular, and physiological domains, it is still difficult to say whether the post-acute sequelae of COVID-19 directly correspond to the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This work hypothesizes that neutrophils and neutrophil extracellular traps (NETs) production are at the interconnection of three positive feedback loops which are initiated in the acute phase of SARS-CoV-2 infection, and which involve inflammation, immunothrombosis, and autoimmunity. This phenomenon could be favored by the fact that SARS-CoV-2 may directly bind and penetrate neutrophils. The ensuing strong neutrophil stimulation leads to a progressive amplification of an exacerbated and uncontrolled NETs production, potentially persisting for months beyond the acute phase of infection. This continuous self-stimulation of neutrophils leads, in turn, to systemic inflammation, micro-thromboses, and the production of autoantibodies, whose significant consequences include the persistence of endothelial and multiorgan damage, and vascular complications.}, } @article {pmid39189008, year = {2024}, author = {Krishna, BA and Metaxaki, M and Sithole, N and Landín, P and Martín, P and Salinas-Botrán, A}, title = {Cardiovascular disease and covid-19: A systematic review.}, journal = {International journal of cardiology. Heart & vasculature}, volume = {54}, number = {}, pages = {101482}, pmid = {39189008}, issn = {2352-9067}, abstract = {BACKGROUND: Cardiovascular complications of COVID-19 are numerous and aspects of this phenomenon are not well known. The main objective of this manuscript is a systematic review of the acute and chronic cardiovascular complications secondary to COVID-19.

METHODS: A systematic review of the literature through Medline via PubMed was conducted (2020-2024).

RESULTS: There is a plethora of effects of COVID-19 on the heart in the acute setting. Here we discuss pathophysiology, myocardial infarctions, heart failure, Takotsubo Cardiomyopathy, myocardial injury, myocarditis and arrhythmias that are caused by COVID-19. Additionally, these cardiovascular injuries can linger and may be an underlying cause of some Long COVID symptoms.

CONCLUSIONS: Cardiovascular complications of COVID-19 are numerous and life-threatening. Long COVID can affect cardiovascular health. Microclotting induced by SARS-CoV-2 infection could be a therapeutic target for some aspects of Long Covid.}, } @article {pmid39188722, year = {2024}, author = {Jang, S and Hong, W and Moon, Y}, title = {Obesity-compromised immunity in post-COVID-19 condition: a critical control point of chronicity.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1433531}, pmid = {39188722}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/complications ; *Obesity/immunology/complications ; *SARS-CoV-2/immunology/physiology ; Inflammation/immunology ; Chronic Disease ; Adipose Tissue/immunology/metabolism ; T-Lymphocytes/immunology ; Immunity, Humoral ; }, abstract = {Post-COVID-19 condition is recognized as a multifactorial disorder, with persistent presence of viral antigens, discordant immunity, delayed viral clearance, and chronic inflammation. Obesity has emerged as an independent risk factor for both SARS-CoV-2 infection and its subsequent sequelae. In this study, we aimed to predict the molecular mechanisms linking obesity and post-COVID-19 distress. Viral antigen-exposed adipose tissues display remarkable levels of viral receptors, facilitating viral entry, deposition, and chronic release of inflammatory mediators and cells in patients. Subsequently, obesity-associated inflammatory insults are predicted to disturb cellular and humoral immunity by triggering abnormal cell differentiation and lymphocyte exhaustion. In particular, the decline in SARS-CoV-2 antibody titers and T-cell exhaustion due to chronic inflammation may account for delayed virus clearance and persistent activation of inflammatory responses. Taken together, obesity-associated defective immunity is a critical control point of intervention against post-COVID-19 progression, particularly in subjects with chronic metabolic distress.}, } @article {pmid39188336, year = {2024}, author = {Motilal, S and Rampersad, R and Adams, M and Goon Lun, S and Ramdhanie, A and Ruiz, T and Shah, A and Wilkinson, A and Lewis, J}, title = {Randomized Controlled Trials for Post-COVID-19 Conditions: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e67603}, pmid = {39188336}, issn = {2168-8184}, abstract = {Post-coronavirus disease 2019 (COVID-19) syndrome or condition (PCS) is defined as new onset symptoms for at least three months following COVID-19 infection that has persisted for at least two months. Given the global sequelae of COVID-19, there is an urgent need for effective PCS interventions. The aim of this study was to systematically review all interventions for PCS tested in randomized controlled trials. In this International Prospective Register of Systematic Reviews (PROSPERO) registered (CRD42023415835) systematic review, PubMed, Google Scholar, and ClinicalTrials.gov databases were searched between 1st January 2020 and 30th April 2023. Inclusion criteria were (1) randomized controlled trials that tested interventions for (2) PCS as defined above. Studies were independently reviewed, and final decisions regarding extracted data and risk of bias were made by consensus. Trial findings were summarized qualitatively. The review included 23 trials with 1,916 subjects (mean age 44.9, 25.8% males) from 10 countries. The predominant symptom or function targeted by the interventions were general long COVID-19 symptoms (35%), fatigue (30%), breathlessness (17%), olfactory (17%), and brain function (9%). Overall, the majority of trials (74%) were at high risk of bias. A range of interventions were identified, including physical therapies, dietary and regenerative treatments, electrical stimulation, and digital wellness programs with variable effects. While a diverse range of interventions for PCS have been tested, their effectiveness varies, with threats to validity in most studies. Trials focusing on PCS mental health disorders, musculoskeletal complaints, and children are needed. Well-designed RCTs are needed to establish definitive interventions for PCS.}, } @article {pmid39187623, year = {2024}, author = {Kow, CS and Ramachandram, DS and Hasan, SS and Thiruchelvam, K}, title = {The potential role of factor XI inhibitors in managing long COVID.}, journal = {Journal of thrombosis and thrombolysis}, volume = {57}, number = {8}, pages = {1363-1364}, pmid = {39187623}, issn = {1573-742X}, } @article {pmid39187577, year = {2024}, author = {Patterson, BK and Guevara-Coto, J and Mora, J and Francisco, EB and Yogendra, R and Mora-Rodríguez, RA and Beaty, C and Lemaster, G and Kaplan DO, G and Katz, A and Bellanti, JA}, title = {Long COVID diagnostic with differentiation from chronic lyme disease using machine learning and cytokine hubs.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {19743}, pmid = {39187577}, issn = {2045-2322}, mesh = {Humans ; *Machine Learning ; *COVID-19/diagnosis ; *Lyme Disease/diagnosis ; Diagnosis, Differential ; *Cytokines/metabolism ; Chronic Disease ; Sensitivity and Specificity ; Male ; Female ; Algorithms ; SARS-CoV-2/isolation & purification ; Middle Aged ; Post-Lyme Disease Syndrome/diagnosis ; Adult ; }, abstract = {The absence of a long COVID (LC) or post-acute sequelae of COVID-19 (PASC) diagnostic has profound implications for research and potential therapeutics given the lack of specificity with symptom-based identification of LC and the overlap of symptoms with other chronic inflammatory conditions. Here, we report a machine-learning approach to LC/PASC diagnosis on 347 individuals using cytokine hubs that are also capable of differentiating LC from chronic lyme disease (CLD). We derived decision tree, random forest, and gradient-boosting machine (GBM) classifiers and compared their diagnostic capabilities on a dataset partitioned into training (178 individuals) and evaluation (45 individuals) sets. The GBM model generated 89% sensitivity and 96% specificity for LC with no evidence of overfitting. We tested the GBM on an additional random dataset (106 LC/PASC and 18 Lyme), resulting in high sensitivity (97%) and specificity (90%) for LC. We constructed a Lyme Index confirmatory algorithm to discriminate LC and CLD.}, } @article {pmid39187064, year = {2024}, author = {Snowden, J and Weakley, K}, title = {Diagnosing, managing, and studying long-COVID syndromes in children and adolescents in rural and underserved populations.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {133}, number = {5}, pages = {516-521}, doi = {10.1016/j.anai.2024.08.028}, pmid = {39187064}, issn = {1534-4436}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/therapy ; Child ; Adolescent ; *Rural Population ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Vulnerable Populations ; Health Services Accessibility ; Medically Underserved Area ; Pandemics ; }, abstract = {The COVID-19 pandemic has arguably had its greatest impact in rural and other historically hard-to-reach populations. Families in rural and underserved communities experienced COVID-19 infections at a higher rate than did their peers in other groups and experienced disproportionate morbidity and mortality. Without careful design and implementation of resources, children in these areas are also at risk of being disproportionately affected by long-term sequelae of SARS-CoV-2 infections, such as "long COVID" syndromes. Increased frequency and severity of COVID-19 infections, decreased access to health care and supporting services, environmental and social structure factors that exacerbate post-acute sequelae of COVID-19, and increased baseline frequency of health disorders that may complicate post-COVID issues, such as higher rates of obesity, asthma, diabetes, and mental health disorders, all place children and adolescents in under-resourced areas at significant risk. Unfortunately, children and adolescents in these areas have been historically under-represented in clinical research. Not only are fewer studies published with participants in rural and underserved communities, but these studies more often exhibit lower quality, with fewer randomized controlled trials and multicenter studies. This gap not only deprives people in rural and underserved areas of the country of access to cutting-edge therapy, but it also risks "evidence-based" solutions that are not generalizable because they cannot be implemented in the areas disproportionately affected by many health conditions such as long COVID. These factors significantly impede our ability to provide appropriate medical care for underserved communities. This review will discuss the impact of COVID-19 in rural and underserved communities and the factors that must be considered in designing evidence-based long-COVID solutions for children and adolescents in these areas.}, } @article {pmid39186606, year = {2024}, author = {Visvabharathy, L and Dalil, N and Leonor, L and Zhu, C and Orban, ZS and Jimenez, M and Lim, PH and Penaloza-MacMaster, P and Koralnik, IJ}, title = {Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC.}, journal = {ImmunoHorizons}, volume = {8}, number = {8}, pages = {577-585}, pmid = {39186606}, issn = {2573-7732}, support = {DP2 DA051912/DA/NIDA NIH HHS/United States ; U54 EB027049/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology/blood ; Male ; *SARS-CoV-2/immunology ; Female ; Middle Aged ; Adult ; Aged ; Autoimmunity/immunology ; Fatigue/immunology ; Antibodies, Viral/blood/immunology ; Breakthrough Infections ; }, abstract = {Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.}, } @article {pmid39186150, year = {2024}, author = {Ejalonibu, H and Amah, A and Aburub, A and Kumar, P and Frederick, DE and Groot, G}, title = {A review of Patient Reported Outcome Measures (PROMs) for characterizing Long COVID (LC)-merits, gaps, and recommendations.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {101}, pmid = {39186150}, issn = {2509-8020}, support = {Strategy for Patient-Oriented Research//Strategy for Patient-Oriented Research/ ; }, mesh = {*Patient Reported Outcome Measures ; Humans ; *COVID-19/epidemiology/psychology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Psychometrics/methods/instrumentation ; Quality of Life ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Individuals may experience a range of symptoms after the clearance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This condition is termed long COVID (LC) or Post-COVID-19 condition (PCC). Despite the appreciable number of symptoms documented to date, one key challenge remains in the robust characterization of LC outcomes. This review aimed to assess the properties, identify gaps, and provide recommendations for relevant descriptive and evaluative Patient-Reported Outcome Measurement (PROM) instruments that can be used to comprehensively characterize LC.

METHODS: To achieve this objective, we identified and reviewed descriptive and evaluative PROM instruments that have been developed and validated to date with people living with LC. Our review assessed their properties, identified gaps, and recommended PROMs suitable for characterizing LC. To ensure a comprehensive and robust characterization of LC, we next identified, reviewed, and selected (with the input of patient partners) PROMs associated with the most frequently reported LC symptoms. The evaluation criteria included psychometric evidence, mode of delivery, cost, and administration time.

RESULTS: Traditional matrix mapping revealed Post-COVID Functional Status Scale (PCFS) as a choice instrument for capturing LC outcomes largely because of the comprehensive domains it covered, and the number of psychometric evidence reported in literatures. This instrument can be effectively paired with the Fatigue Severity Scale (FSS), Montreal Cognitive Assessment (MoCA), Patient Health Questionnaire (PHQ-9), Headache Impact Test (HIT), Pittsburgh Sleep Quality Index (PSQI), and DePaul Symptom Questionnaire (DSQ-PEM) to characterize fatigue, cognitive impairment, depression/anxiety, headache, sleeplessness, and post-exertional malaise respectively.

CONCLUSION: Our paper identified appropriate PROM instruments that can effectively capture the diverse impacts of LC. By utilizing these validated instruments, we can better understand and manage LC.}, } @article {pmid39185970, year = {2024}, author = {Roush, K}, title = {New Report Highlights the Impact of Long COVID.}, journal = {The American journal of nursing}, volume = {124}, number = {9}, pages = {12}, doi = {10.1097/01.NAJ.0001050764.33521.df}, pmid = {39185970}, issn = {1538-7488}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; SARS-CoV-2 ; }, abstract = {Debilitating symptoms, affecting multiple organ systems, can last years.}, } @article {pmid39185419, year = {2024}, author = {Sumi, T and Harada, K}, title = {Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1329162}, pmid = {39185419}, issn = {1664-3224}, mesh = {Humans ; *Antiviral Agents/therapeutic use ; *SARS-CoV-2/immunology/physiology ; *COVID-19/prevention & control/immunology/complications ; *Post-Acute COVID-19 Syndrome ; *COVID-19 Vaccines/immunology ; *Viral Load ; COVID-19 Drug Treatment ; Vaccination ; Models, Theoretical ; }, abstract = {INTRODUCTION: Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency.

METHODS: A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed.

RESULTS AND DISCUSSION: Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC.}, } @article {pmid39185269, year = {2024}, author = {Stewart, S and Heald, A and Pyne, Y and Bakerly, ND}, title = {Menopause symptom prevalence in three post-COVID-19 syndrome clinics in England: A cross-sectional analysis.}, journal = {IJID regions}, volume = {12}, number = {}, pages = {100405}, pmid = {39185269}, issn = {2772-7076}, abstract = {OBJECTIVES: There is an overlap between symptoms of perimenopause/menopause and post-COVID syndrome and there is a concern that some female patients referred to post-COVID syndrome clinics may have undiagnosed perimenopause/menopause. However, the prevalence of such symptoms in this population is unknown.

METHODS: Cross-sectional analysis of 122 women's health questionnaires as part of a service improvement project in three National Health Service post-COVID syndrome clinics in England. The primary outcomes were prevalence of menopause symptoms and association between the total menopause symptom questionnaire (MSQ) score and the key predictors.

RESULTS: Age group 40-54 years showed the highest prevalence of most individual symptoms and the highest mean total MSQ score (36.4; confidence interval [CI] 32.3-40.6), correlating clinically with the onset of perimenopause/menopause. Regression modeling shows a significant positive parabolic relationship between age and total MSQ score. Age group 40-54 years is associated with a 6.60-point higher (CI 1.31-11.9) total MSQ score than the age group 55-79 years; an increase of one index of multiple deprivation quintile is associated with a 2.85-point lower (CI -1.24 to -4.45) total MSQ score; presence of a gynecologic diagnosis is associated with a 6.31-point higher (CI 1.32-11.3) total MSQ score. A total of 51% of patients who menstruate reported menstrual disturbance with COVID-19 infection and 21% with COVID-19 vaccination.

CONCLUSIONS: Symptoms possibly attributable to perimenopause and menopause were highly prevalent among female patients attending post-COVID syndrome clinics in Greater Manchester, England. Our findings provide key prevalence estimates and significant predictors of MSQ scores that are vital for future research, clinical practice, and policy.}, } @article {pmid39183848, year = {2024}, author = {Bhuvaneshwar, K and Madhavan, S and Gusev, Y}, title = {Integrative genomic analysis of the lung tissue microenvironment in SARS-CoV-2 and NL63 patients.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e32772}, pmid = {39183848}, issn = {2405-8440}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected over 700 million people, and caused over 7 million deaths throughout the world as of April 2024, and continues to affect people through seasonal waves. While over 675 million people have recovered from this disease globally, the lingering effects of the disease are still under study. Long term effects of SARS-CoV-2 infection, known as 'long COVID,' include a wide range of symptoms including fatigue, chest pain, cellular damage, along with a strong innate immune response characterized by inflammatory cytokine production. Three years after the pandemic, data about long covid studies are finally emerging. More clinical studies and clinical trials are needed to understand and determine the factors that predispose individuals to these long-term side effects. In this methodology paper, our goal was to apply data driven approaches in order to explore the multidimensional landscape of infected lung tissue microenvironment to better understand complex interactions between viral infection, immune response and the lung microbiome of patients with (a) SARS-CoV-2 virus and (b) NL63 coronavirus. The samples were analyzed with several machine learning tools allowing simultaneous detection and quantification of viral RNA amount at genome and gene level; human gene expression and fractions of major types of immune cells, as well as metagenomic analysis of bacterial and viral abundance. To contrast and compare specific viral response to SARS-COV-2, we analyzed deep sequencing data from additional cohort of patients infected with NL63 strain of corona virus. Our correlation analysis of three types of RNA-seq based measurements in patients i.e. fraction of viral RNA (at genome and gene level), Human RNA (transcripts and gene level) and bacterial RNA (metagenomic analysis), showed significant correlation between viral load as well as level of specific viral gene expression with the fractions of immune cells present in lung lavage as well as with abundance of major fractions of lung microbiome in COVID-19 patients. Our methodology-based proof-of-concept study has provided novel insights into complex regulatory signaling interactions and correlative patterns between the viral infection, inhibition of innate and adaptive immune response as well as microbiome landscape of the lung tissue. These initial findings could provide better understanding of the diverse dynamics of immune response and the side effects of the SARS-CoV-2 infection and demonstrates the possibilities of the various types of analyses that could be performed from this type of data.}, } @article {pmid39183811, year = {2024}, author = {Zhang, X and Anzalone, AJ and Dai, D and Cochran, G and Dai, R and Rupp, ME and , }, title = {Chronic Lung Disease as a Risk Factor for Long COVID in Patients Diagnosed With Coronavirus Disease 2019: A Retrospective Cohort Study.}, journal = {Open forum infectious diseases}, volume = {11}, number = {8}, pages = {ofae424}, pmid = {39183811}, issn = {2328-8957}, support = {U54 GM104942/GM/NIGMS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) often experience persistent symptoms, known as postacute sequelae of COVID-19 or long COVID, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Chronic lung disease (CLD) has been identified in small-scale studies as a potential risk factor for long COVID.

METHODS: This large-scale retrospective cohort study using the National COVID Cohort Collaborative data evaluated the link between CLD and long COVID over 6 months after acute SARS-CoV-2 infection. We included adults (aged ≥18 years) who tested positive for SARS-CoV-2 during any of 3 SARS-CoV-2 variant periods and used logistic regression to determine the association, considering a comprehensive list of potential confounding factors, including demographics, comorbidities, socioeconomic conditions, geographical influences, and medication.

RESULTS: Of 1 206 021 patients, 1.2% were diagnosed with long COVID. A significant association was found between preexisting CLD and long COVID (adjusted odds ratio [aOR], 1.36). Preexisting obesity and depression were also associated with increased long COVID risk (aOR, 1.32 for obesity and 1.29 for depression) as well as demographic factors including female sex (aOR, 1.09) and older age (aOR, 1.79 for age group 40-65 [vs 18-39] years and 1.56 for >65 [vs 18-39] years).

CONCLUSIONS: CLD is associated with higher odds of developing long COVID within 6 months after acute SARS-CoV-2 infection. These data have implications for identifying high-risk patients and developing interventions for long COVID in patients with CLD.}, } @article {pmid39183264, year = {2024}, author = {Suski, M and Olszanecka, A and Stachowicz, A and Kiepura, A and Terlecki, M and Madej, J and Rajzer, M and Olszanecki, R}, title = {Alterations in plasma proteome during acute COVID-19 and recovery.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {131}, pmid = {39183264}, issn = {1528-3658}, support = {SZPITALE-JEDNOIMIENNE/18/2020//Narodowe Centrum Badań i Rozwoju/ ; }, mesh = {Humans ; *COVID-19/blood ; *Proteome/metabolism ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; *Blood Proteins/metabolism/analysis ; Aged ; Adult ; Proteomics/methods ; Acute-Phase Proteins/metabolism ; }, abstract = {BACKGROUND: The severe course of COVID-19 causes cardiovascular injuries, although the mechanisms involved are still not fully recognized, linked, and understood. Their characterization is of great importance with the establishment of the conception of post-acute sequelae of COVID-19, referred to as long COVID, where blood clotting and endothelial abnormalities are believed to be the key pathomechanisms driving circulatory system impairment.

METHODS: The presented study investigates temporal changes in plasma proteins in COVID-19 patients during hospitalization due to SARS-CoV-2 infection and six months after recovery by targeted SureQuant acquisition using PQ500 panel.

RESULTS: In total, we identified 167 proteins that were differentially regulated between follow-up and hospitalization, which functionally aggregated into immune system activation, complement and coagulation cascades, interleukins signalling, platelet activation, and extracellular matrix organization. Furthermore, we found that temporal quantitative changes in acute phase proteins correlate with selected clinical characteristics of COVID-19 patients.

CONCLUSIONS: In-depth targeted proteome investigation evidenced substantial changes in plasma protein composition of patients during and recovering from COVID-19, evidencing a wide range of functional pathways induced by SARS-CoV-2 infection. In addition, we show that a subset of acute phase proteins, clotting cascade regulators and lipoproteins could have clinical value as potential predictors of long-term cardiovascular events in COVID-19 convalescents.}, } @article {pmid39183058, year = {2024}, author = {Dempsey, B and Madan, I and Stevelink, SAM and Lamb, D}, title = {Long COVID among healthcare workers: a narrative review of definitions, prevalence, symptoms, risk factors and impacts.}, journal = {British medical bulletin}, volume = {151}, number = {1}, pages = {16-35}, pmid = {39183058}, issn = {1471-8391}, support = {NIHR300592//National Institute for Health and Care Research/ ; //Maudsley NHS Foundation Trust/ ; //National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre/ ; CF/01/22//Colt Foundation/ ; }, mesh = {Humans ; *Health Personnel/statistics & numerical data ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID (LC) occurs when people experience symptoms for weeks, months or even years after a COVID-19 infection. This review looks at research exploring the LC definitions, prevalence, symptoms, risk factors, and associated impacts in research on healthcare workers (HCWs).

DATA SOURCES: We systematically searched five electronic databases (CINAHL, EMBASE, Medline, PsycInfo and PubMed) and compiled a narrative literature review based on 56 relevant studies.

AREAS OF AGREEMENT: LC is prevalent among HCWs who become infected by COVID-19. Many of the most frequent symptoms associated with LC in the general population are also reported among HCWs. Some risk factors for LC are also similar to those in the general population, such as female sex, older age, and having a pre-existing respiratory illness.

AREAS OF CONTROVERSY: The mechanism(s) responsible for LC remains unknown. A variety of terms, timeframes and symptoms are used to define LC, creating difficulties in comparing results across studies. Much of the research is cross-sectional and fails to explore the impacts that prolonged symptoms have on HCWs' personal and professional lives.

GROWING POINTS: The need to support HCWs with LC is clear. Identifying the mechanism(s) responsible for LC is a key priority, as this will inform treatments.

AREAS FOR DEVELOPING RESEARCH: Future research should move towards a standard definition for LC. Greater attention should be paid to longitudinal and qualitative studies, which could give insights into prognosis, lived experience and work participation. Finally, studies evaluating treatments suitable for people with LC are timely.}, } @article {pmid39182422, year = {2024}, author = {Ohira, M and Osada, T and Kimura, H and Sano, T and Takao, M}, title = {Post-acute sequelae of SARS-CoV-2 mimic: An important neurological condition.}, journal = {Journal of the neurological sciences}, volume = {465}, number = {}, pages = {123199}, doi = {10.1016/j.jns.2024.123199}, pmid = {39182422}, issn = {1878-5883}, mesh = {Humans ; *COVID-19/complications/diagnosis ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Aged ; SARS-CoV-2 ; Nervous System Diseases/etiology/diagnosis ; Antibodies, Viral/blood ; }, abstract = {BACKGROUND AND OBJECTIVES: In 2024, the sequalae of the acute phase of coronavirus disease-19 (COVID-19) infection, which include neurological symptoms and are commonly referred to as long COVID or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), continue to be a substantial health concern; however, similar symptoms are observed in individuals with no previous COVID-19 infection.

METHODS: This was a single-center, retrospective, descriptive case series study. Data were obtained from patients who visited our outpatient clinic specializing in PASC between June 1, 2021, and May 31, 2023. We compared antibody test results between patients with confirmed acute phase infection and those without. We compared differences in demographic and clinical characteristics between patients with positive results during the acute phase of COVID-19 infection and positive anti-SARS-CoV-2 antibody tests (true-PASC), and those with neither (PASC-mimic).

RESULTS: Of 437 patients diagnosed with PASC according to World Health Organization criteria, 222 underwent COVID-19 antibody tests. Of these, 193 patients (86.9%) had a history of confirmed acute phase infection, whereas 29 (13.1%) did not. Of the former, 186 patients (96.4%) were seropositive for anti-nucleotide SARS-CoV-2 antibodies (true-PASC), whereas 19 of the latter tested seronegative for anti-nucleotide SARS-CoV-2 antibodies (PASC-mimic). There were no significant differences in symptom characteristics between true-PASC and PASC-mimic participants.

CONCLUSIONS: It was difficult to identify any clinical features to aid in diagnosing PASC without confirmation of acute COVID-19 infection. The findings indicate the existence of a "PASC-mimic" condition that should be acknowledged and excluded in future PASC-related research studies.}, } @article {pmid39182371, year = {2024}, author = {Nkengue, MJ and Zeng, X and Koehl, L and Tao, X and Dassonville, F and Dumont, N and Ye-Lehmann, S and Akwa, Y and Ye, H}, title = {An intelligent garment for long COVID-19 real-time monitoring.}, journal = {Computers in biology and medicine}, volume = {181}, number = {}, pages = {109067}, doi = {10.1016/j.compbiomed.2024.109067}, pmid = {39182371}, issn = {1879-0534}, mesh = {Humans ; *COVID-19 ; *Wearable Electronic Devices ; *SARS-CoV-2 ; *Electrocardiography ; *Heart Rate/physiology ; Monitoring, Physiologic/instrumentation/methods ; Signal Processing, Computer-Assisted ; Male ; Machine Learning ; Oxygen Saturation ; Female ; Body Temperature ; }, abstract = {As monitoring and diagnostic tools for long COVID-19 cases, wearable systems and supervised learning-based medical image analysis have proven to be useful. Current research on these two technical roadmaps has various drawbacks, despite their respective benefits. Wearable systems allow only the real-time monitoring of physiological parameters (heart rate, temperature, blood oxygen saturation, or SpO2). Therefore, they are unable to conduct in-depth investigations or differentiate COVID-19 from other illnesses that share similar symptoms. Medical image analysis using supervised learning-based models can be used to conduct in-depth analyses and provide precise diagnostic decision support. However, these methods are rarely used for real-time monitoring. In this regard, we present an intelligent garment combining the precision of supervised learning-based models with real-time monitoring capabilities of wearable systems. Given the relevance of electrocardiogram (ECG) signals to long COVID-19 symptom severity, an explainable data fusion strategy based on multiple machine learning models uses heart rate, temperature, SpO2, and ECG signal analysis to accurately assess the patient's health status. Experiments show that the proposed intelligent garment achieves an accuracy of 97.5 %, outperforming most of the existing wearable systems. Furthermore, it was confirmed that the two physiological indicators most significantly affected by the presence of long COVID-19 were SpO2 and the ST intervals of ECG signals.}, } @article {pmid39181334, year = {2024}, author = {Darbyshire, J and Greenhalgh, T and Bakerly, ND and Balasundaram, K and Baley, S and Ball, M and Bullock, E and Cooper, R and Davies, H and De Kock, JH and Echevarria, C and Elkin, S and Evans, R and Falope, Z and Flynn, C and Fraser, E and Halpin, S and Jones, S and Lardner, R and Lee, C and Lovett, A and Masey, V and Master, H and Mir, G and Mosley, A and Mullard, J and O'Connor, RJ and Parkin, A and Pick, A and Scott, J and Smith, N and Tucker, E and Williams, P and Winch, D and Wood, C and Sivan, M and , }, title = {Improving quality in adult long covid services: Findings from the LOCOMOTION quality improvement collaborative.}, journal = {Clinical medicine (London, England)}, volume = {24}, number = {5}, pages = {100237}, pmid = {39181334}, issn = {1473-4893}, mesh = {Humans ; *COVID-19/epidemiology ; *Quality Improvement/organization & administration ; SARS-CoV-2 ; United Kingdom ; Post-Acute COVID-19 Syndrome ; Adult ; }, abstract = {The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales. The NIHR-funded LOCOMOTION project implemented a UK-wide quality improvement collaborative involving ten of these clinics, which ran from 2021 to 2023. At regular online meetings held approximately 8-weekly, participants prioritised topics, discussed research evidence and guidelines, and presented exemplar case histories and clinic audits. A patient advisory group also held a priority-setting exercise, participated in quality meetings and undertook a service evaluation audit. The goal of successive quality improvement cycles aimed at changing practice to align with evidence was sometimes hard to achieve because definitive evidence did not yet exist in this new condition; many patients had comorbidities; and clinics were practically constrained in various ways. Nevertheless, much progress was made and a series of 'best practice' guides was produced, covering general assessment and management; breathing difficulties; orthostatic tachycardia and other autonomic symptoms; fatigue and cognitive impairment; and vocational rehabilitation. This paper summarises key findings with the frontline clinician in mind.}, } @article {pmid39180988, year = {2024}, author = {Kananian, S and Nemani, A and Stangier, U}, title = {Risk and protective factors for the severity of long COVID - A network analytic perspective.}, journal = {Journal of psychiatric research}, volume = {178}, number = {}, pages = {291-297}, doi = {10.1016/j.jpsychires.2024.08.031}, pmid = {39180988}, issn = {1879-1379}, mesh = {Humans ; *COVID-19 ; Male ; Female ; Adult ; Middle Aged ; *Protective Factors ; Risk Factors ; Severity of Illness Index ; Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Young Adult ; Mental Disorders/epidemiology ; Depression/epidemiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND AND OBJECTIVES: In light of the late stage of COVID-19 pandemic, the occurrence of persistent symptoms after COVID-19 infection has become more frequent. To date, there are no standardized treatments. Underlying mechanisms, risk and protective factors for severe persisting symptoms should be investigated to develop effective interventions.

METHODS: An online questionnaire was used to assess gender, presence of prior mental disorder, severity of COVID-19 infection, and social connectedness (SCS-R) to determine their influence on symptom severity of persisting symptoms. The sample used to examine risk and protective factors consisted of 693 participants.

RESULTS: The analysis revealed no significant gender differences for severity of persisting symptoms. However, prior mental health condition was associated with severity of persisting symptoms. Moreover, there was a positive association between symptom severity during COVID-19 infection and Post COVID 19. Social connectedness was found to be negatively associated with Post COVID 19 symptoms. Social connectedness was shown to be negatively associated with depressive symptoms and disordered self-organization. The symptoms of energy loss and concentration had the highest centrality.

CONCLUSION: The results of the study indicate that severity of post-covid symptoms is associated with higher levels of psychopathological symptoms and a lower level of social connectedness. In conclusion, social connectedness may be an important factor in the development of post-COVID symptoms and should be considered for future interventions. The results from the network analyses provide a first step for a more granular syndrome profile.}, } @article {pmid39180511, year = {2024}, author = {Smith, MM and Melrose, J}, title = {Impaired instructive and protective barrier functions of the endothelial cell glycocalyx pericellular matrix is impacted in COVID-19 disease.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {16}, pages = {e70033}, pmid = {39180511}, issn = {1582-4934}, support = {//Melrose Personal Research Fund/ ; }, mesh = {Humans ; *Glycocalyx/metabolism ; *COVID-19/metabolism/pathology/virology ; *Endothelial Cells/metabolism/pathology ; *SARS-CoV-2/metabolism/drug effects ; *Blood-Brain Barrier/metabolism/drug effects ; Glycosaminoglycans/metabolism ; }, abstract = {The aim of this study was to review the roles of endothelial cells in normal tissue function and to show how COVID-19 disease impacts on endothelial cell properties that lead to much of its associated symptomatology. This places the endothelial cell as a prominent cell type to target therapeutically in the treatment of this disorder. Advances in glycosaminoglycan analytical techniques and functional glycomics have improved glycosaminoglycan mimetics development, providing agents that can more appropriately target various aspects of the behaviour of the endothelial cell in-situ and have also provided polymers with potential to prevent viral infection. Thus, promising approaches are being developed to combat COVID-19 disease and the plethora of symptoms this disease produces. Glycosaminoglycan mimetics that improve endothelial glycocalyx boundary functions have promising properties in the prevention of viral infection, improve endothelial cell function and have disease-modifying potential. Endothelial cell integrity, forming tight junctions in cerebral cell populations in the blood-brain barrier, prevents the exposure of the central nervous system to circulating toxins and harmful chemicals, which may contribute to the troublesome brain fogging phenomena reported in cognitive processing in long COVID disease.}, } @article {pmid39179487, year = {2024}, author = {Hromić-Jahjefendić, A and Mahmutović, L and Sezer, A and Bećirević, T and Rubio-Casillas, A and Redwan, EM and Uversky, VN}, title = {The intersection of microbiome and autoimmunity in long COVID-19: Current insights and future directions.}, journal = {Cytokine & growth factor reviews}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cytogfr.2024.08.002}, pmid = {39179487}, issn = {1879-0305}, abstract = {Long COVID-19 affects a significant percentage of patients and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system referring to the ability of immune system to constantly monitor the body for signs of infection, disease, or abnormal cells; altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes-interventions that target the microbiome-may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. More research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.}, } @article {pmid39179415, year = {2024}, author = {Solopov, PA and Colunga Biancatelli, RML and Day, T and Gregory, B and Sharlow, ER and Lazo, JS and Catravas, JD}, title = {KVX-053, a Protein Tyrosine Phosphatase 4A3 inhibitor, ameliorates SARS-CoV-2 Spike protein subunit 1 - induced acute lung injury in mice.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1124/jpet.124.002154}, pmid = {39179415}, issn = {1521-0103}, support = {P30 CA044579/CA/NCI NIH HHS/United States ; R43 HL158409/HL/NHLBI NIH HHS/United States ; }, abstract = {The Acute Respiratory Distress Syndrome (ARDS), often preceded by acute lung injury (ALI), is characterized by the accumulation of inflammatory fluid in the lung alveoli, leaky alveolar epithelium and endothelium, and overexpression of pro-inflammatory cytokines. This progression from ALI to ARDS is a major contributor to the high mortality observed in COVID-19 patients. The Spike protein of SARS-CoV-2 binds to lung ACE2 and, in addition to facilitating viral cell entry, it plays an important role in the development of ALI and ARDS, especially in the later phases of COVID-19 as well as long COVID. Protein tyrosine phosphatase (PTP) 4A3 is a key mediator of ARDS pathology. This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19 associated ALI. Intratracheal administration of SARS-CoV-2 Spike protein Subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines, structural lung injury and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings provide the first evidence supporting a role for PTP4A3 in the development of SARS-CoV-2- mediated ALI. Significance Statement This study tested the hypothesis that targeting PTP4A3 would prevent COVID-19 associated ALI/ARDS. Intratracheal administration of SARS-CoV-2 Spike protein Subunit 1 to K18-hACE2 transgenic mice expressing human ACE2 elicited pulmonary and systemic inflammation, leaky alveoli, overexpression of cytokines and chemokines, structural lung injury and lung dysfunction; all these symptoms were ameliorated by the selective, allosteric inhibitor of PTP4A3, KVX-053. These findings suggest that this novel PTP4A3 inhibitor may be useful against COVID-19 and potentially other viral-induced ARDS.}, } @article {pmid39179099, year = {2024}, author = {Elliott, MR and O'Connor, AE and Marshall, GD}, title = {Inflammatory pathways in patients with post-acute sequelae of COVID-19: The role of the clinical immunologist.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {133}, number = {5}, pages = {507-515}, pmid = {39179099}, issn = {1534-4436}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; U19 AT010838/AT/NCCIH NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; *Inflammation/immunology ; }, abstract = {As the SARS-CoV-2 pandemic progressed, some survivors noted prolonged symptoms after acute infection, termed post-acute sequelae of COVID-19 (PASC) or "long COVID." PASC is a significant clinical and public health concern that adversely affects patients' quality of life, income, and health care expenses. Moreover, PASC symptoms are highly heterogeneous, the most common being fatigue and cognitive impairment, and they likely reflect a spectrum of clinical phenotypes. The proposed role of persistent inflammation is one of leading pathophysiological theories. This review article addresses these proposed mechanisms of persistent and aberrant inflammation, their clinical evaluation, and theoretical approaches to management. A review of public databases was used to collect literature for the review. The literature supports a prominent role of persistent and aberrant inflammation as a major contributor to the symptoms of PASC. Proposed mechanisms for persistent inflammation include reactivation of latent viruses, viral persistence, loss of immunoregulatory pathways, autoimmune mechanisms, and/or mast cell dysregulation. Persistent inflammation may result in constitutional symptoms such as fatigue, brain fog, body aches, and/or organ-specific dysfunction, such as gastrointestinal dysregulation and myocardial inflammation. There are no approved or even proven therapies for PASC at this time, but some studies have identified therapeutic options that may either reduce the risk for progression to PASC or decrease symptom burden. Laboratory evaluation and therapeutic options are limited and require further investigation to establish their clinical value. A more refined definition of PASC is needed to address the wide variety of clinical presentations, pathophysiology, and therapeutic options.}, } @article {pmid39178603, year = {2024}, author = {Noij, KS and Babu, V and Drews, M and Lockshaw, S and Hermann, L and Malone, LA and Jenks, CM}, title = {Persistent postural perceptual dizziness (PPPD) in pediatric patients after COVID-19 infection.}, journal = {International journal of pediatric otorhinolaryngology}, volume = {184}, number = {}, pages = {112076}, doi = {10.1016/j.ijporl.2024.112076}, pmid = {39178603}, issn = {1872-8464}, support = {U18 HS029920/HS/AHRQ HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Adolescent ; *Dizziness/diagnosis/therapy/etiology ; Child ; Postural Balance/physiology ; SARS-CoV-2 ; Cognitive Behavioral Therapy/methods ; Physical Therapy Modalities ; Post-Acute COVID-19 Syndrome ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Patients with long-COVID suffer from symptoms that continue or develop after a COVID-19 or SARS-CoV-2 infection and are present for four or more weeks after the initial infection. This case series describes a group of previously healthy adolescent patients with long-COVID who were seen in a pediatric vestibular clinic for evaluation of severe dizziness and were diagnosed with persistent postural-perceptual dizziness (PPPD). By presenting their symptoms, management and treatment effects, this study aims to provide a diagnostic and therapeutic framework for providers who encounter these patients.

METHODS: Patient records were reviewed for past medical history, symptoms, physical exam findings, results of audiometric and vestibular testing, dizziness handicap inventory for patient caregiver (DHI-pc) scores, and treatment recommendations. Parents of patients were contacted for a follow up survey to assess treatment adherence and outcomes including changes in symptoms and return to activity.

RESULTS: A series of 9 adolescent patients were referred from a multidisciplinary long-COVID clinic and diagnosed with PPPD. Recommended treatment included vestibular physical therapy, selective serotonin reuptake inhibitor medication, and cognitive behavioral therapy. The majority of patients experienced an improvement in their symptoms, and all patients had improved activity levels and DHI-pc scores after treatment.

CONCLUSION: To the best of our knowledge, no previous reports exist discussing PPPD in long-COVID patients. This case series provides insight into symptom evolution and treatment efficacy in this patient population.}, } @article {pmid39178421, year = {2024}, author = {Farinetti, A and Manenti, A and Mattioli, AV}, title = {Letter: Long COVID in Patients With Peripheral Arterial Disease; the Need for Further Research.}, journal = {Angiology}, volume = {}, number = {}, pages = {33197241278131}, doi = {10.1177/00033197241278131}, pmid = {39178421}, issn = {1940-1574}, } @article {pmid39177216, year = {2024}, author = {Koterba, CH and Considine, CM and Becker, JH and Hoskinson, KR and Ng, R and Vargas, G and Basso, MR and Puente, AE and Lippa, SM and Whiteside, DM}, title = {Neuropsychology practice guidance for the neuropsychiatric aspects of Long COVID.}, journal = {The Clinical neuropsychologist}, volume = {}, number = {}, pages = {1-29}, doi = {10.1080/13854046.2024.2392943}, pmid = {39177216}, issn = {1744-4144}, abstract = {Objective: The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a profound global impact on individual health and well-being in adults and children. While most fully recover from COVID-19, a relatively large subgroup continues to experience persistent physical, cognitive, and emotional/behavioral symptoms beyond the initial infection period. The World Health Organization has termed this phenomenon "Post-COVID-19 Condition" (PCC), better known as "Long COVID." Due to the cognitive and psychosocial symptoms, neuropsychologists often assess and recommend treatment for individuals with Long COVID. However, guidance for neuropsychologists' involvement in clinical care, policy-making, and research has not yet been developed. The authors of this manuscript convened to address this critical gap and develop guidance for clinical neuropsychologists working with patients presenting with Long COVID. Method: Authors include pediatric and adult neuropsychologists with expertise in Long COVID and behavioral health. All authors have been engaged in clinical and research efforts examining the impact of COVID-19. Authors summarized the literature-to-date pertinent to the neuropsychiatric sequelae of Long COVID and developed guidance for neuropsychologists working with individuals with Long COVID. Conclusions: Research findings regarding neuropsychiatric symptoms associated with Long COVID are mixed and limited by methodological differences. As they practice and conduct research, neuropsychologists should remain mindful of the evolving and tenuous nature of the literature.}, } @article {pmid39177056, year = {2024}, author = {Wang, Y and Yang, Z and Zheng, X and Liang, X and Wu, L and Wu, C and Dai, J and Cao, Y and Li, M and Zhou, F}, title = {Cerebral blood flow alterations and host genetic association in individuals with long COVID: A transcriptomic-neuroimaging study.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {}, number = {}, pages = {271678X241277621}, pmid = {39177056}, issn = {1559-7016}, abstract = {Neuroimaging studies have indicated that altered cerebral blood flow (CBF) was associated with the long-term symptoms of postacute sequelae of SARS-CoV-2 infection (PASC), also known as "long COVID". COVID-19 and long COVID were found to be strongly associated with host gene expression. Nevertheless, the relationships between altered CBF, clinical symptoms, and gene expression in the central nervous system (CNS) remain unclear in individuals with long COVID. This study aimed to explore the genetic mechanisms of CBF abnormalities in individuals with long COVID by transcriptomic-neuroimaging spatial association. Lower CBF in the left frontal-temporal gyrus was associated with higher fatigue and worse cognition in individuals with long COVID. This CBF pattern was spatially associated with the expression of 2,178 genes, which were enriched in the molecular functions and biological pathways of COVID-19. Our study suggested that lower CBF is associated with persistent clinical symptoms in long COVID individuals, possibly as a consequence of the complex interactions among multiple COVID-19-related genes, which contributes to our understanding of the impact of adverse CNS outcomes and the trajectory of development to long COVID.}, } @article {pmid39176880, year = {2024}, author = {Katika, A and Zoulias, E and Koufi, V and Malamateniou, F}, title = {Greek Tweets on Long COVID: Topic Modelling Following Sentiment Analysis and ChatGPT Interpretation.}, journal = {Studies in health technology and informatics}, volume = {316}, number = {}, pages = {1977-1978}, doi = {10.3233/SHTI240821}, pmid = {39176880}, issn = {1879-8365}, mesh = {*Social Media ; *COVID-19 ; Greece ; Humans ; Natural Language Processing ; SARS-CoV-2 ; }, abstract = {Long COVID is a disease that makes it hard for patients to get an official diagnosis while it impacts their quality of life. Many people are turning to social networks such as Facebook, WhatsApp, Twitter (now X) to express their opinions and feelings regarding Long COVID. In this paper, positive (or neutral) and negative text messages in the Greek language, posted on the Twitter platform in 2022, regarding Long COVID are analyzed and popular discussion topics are extracted. Analysis revealed that when topic modelling follows sentiment analysis more coherent topics are created. Furthermore, ChatGPT is used to assign a label to each topic that, in turn, is assessed by a human expert.}, } @article {pmid39176874, year = {2024}, author = {Knak, AK and Roheger, M and Wulff, A}, title = {Challenges in Daily Computerized Assessment of Cognitive Functions of Post-COVID Patients.}, journal = {Studies in health technology and informatics}, volume = {316}, number = {}, pages = {1950-1954}, doi = {10.3233/SHTI240815}, pmid = {39176874}, issn = {1879-8365}, mesh = {Humans ; *COVID-19 ; Cognitive Dysfunction ; Diagnosis, Computer-Assisted/methods ; SARS-CoV-2 ; Fatigue ; Post-Acute COVID-19 Syndrome ; Cognition ; }, abstract = {While it would be quite helpful to learn more about the daily fluctuations of fatigue and cognitive impairments of post-COVID patients, their condition can make investigating these especially challenging. By discussing these issues with post-COVID patients and clinical practitioners, we identified six challenges that specifically apply to daily computerized assessment of cognitive functions of post-COVID patients. We proposed solutions for each of the challenges which can be summarized as offering a carefully planned and flexible study design to participants and monitoring their well-being throughout the assessments. We argue that when the proposed precautions are taken, it is feasible to conduct a study that will generate valuable insights into the trajectories of (cognitive) post-COVID symptoms.}, } @article {pmid39175757, year = {2024}, author = {van Lith, TJ and Li, H and van der Wijk, MW and Wijers, NT and Sluis, WM and Wermer, MJH and de Leeuw, FE and Meijer, FJA and Tuladhar, AM}, title = {White matter integrity in hospitalized COVID-19 patients is not associated with short- and long-term clinical outcomes.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1440294}, pmid = {39175757}, issn = {1664-2295}, abstract = {OBJECTIVES: SARS-CoV-2 infection is associated with a decline in functional outcomes; many patients experience persistent symptoms, while the underlying pathophysiology remains unclear. This study investigated white matter (WM) integrity on brain MRI in hospitalized COVID-19 patients and its associations with clinical outcomes, including long COVID.

MATERIALS AND METHODS: We included hospitalized COVID-19 patients and controls from CORONavirus and Ischemic Stroke (CORONIS), an observational cohort study, who underwent MRI-DWI imaging at baseline shortly after discharge (<3 months after positive PCR) and 3 months after baseline scanning. We assessed WM integrity using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) and performed comparisons between groups and within patients. Clinical assessment was conducted at 3 and 12 months with functional outcomes such as modified Rankin Scale (mRS), Post-COVID-19 Functional Status scale (PCFS), Visual Analogue Scale (VAS), and long COVID, cognitive assessment was conducted by the Modified Telephone Interview for Cognitive Status (TICS-M), and the Hospital Anxiety and Depression Scale (HADS) was used to assess mood disorder. Associations between WM integrity and clinical outcomes were evaluated using logistic regression and linear regression.

RESULTS: A total of 49 patients (mean age 59.5 years) showed higher overall peak width of skeletonized mean diffusivity (PSMD) (p = 0.030) and lower neurite density index (NDI) in several WM regions compared with 25 controls at the baseline (p < 0.05; FWE-corrected) but did not remain statistically significant after adjusting for WM hyperintensities. Orientation dispersion index (ODI) increased after 3-month follow-up in several WM regions within patients (p < 0.05), which remained significant after correction for changes in WMH volume. Patients exhibited worse clinical outcomes compared with controls. Low NDI at baseline was associated with worse performance on the Post-COVID-19 Functional Status scale after 12 months (p = 0.018).

CONCLUSION: After adjusting for WMH, hospitalized COVID-19 patients no longer exhibited lower WM integrity compared with controls. WM integrity was generally not associated with clinical assessments as measured shortly after discharge, suggesting that factors other than underlying WM integrity play a role in worse clinical outcomes or long COVID.}, } @article {pmid39175748, year = {2024}, author = {Kiatratdasakul, S and Noisumdaeng, P and Niyomdecha, N}, title = {Biological factors associated with long COVID and comparative analysis of SARS-CoV-2 spike protein variants: a retrospective study in Thailand.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17898}, pmid = {39175748}, issn = {2167-8359}, mesh = {Humans ; Thailand/epidemiology ; *Spike Glycoprotein, Coronavirus/genetics ; *COVID-19/epidemiology/virology ; *SARS-CoV-2/genetics ; Retrospective Studies ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; Mutation ; Aged ; Prevalence ; Young Adult ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (long COVID) refers to the persistence of COVID-19 symptoms or exceptional symptoms following recovery. Even without conferring fatality, it represents a significant global public health burden. Despite many reports on long COVID, the prevalence and data on associated biological factors remain unclear and limited. This research aimed to determine the prevalence of long COVID during the two distinct epidemic periods in Thailand, due to the Delta and Omicron variants of SARS-CoV-2, and to investigate the biological factors associated with long COVID. In addition, the spike protein amino acid sequences of the Delta and Omicron variants were compared to determine the frequency of mutations and their potential biological implications.

METHODS: A retrospective cross-sectional study was established to recruit confirmed COVID-19 participants at Maharat Nakhon Ratchasima Hospital who had recovered for at least three months and were infected between June 2021 and August 2022. The demographic data and long COVID experience were collected via telephone interview. The biological factors were analyzed through binary logistic regression. The datasets of the SARS-CoV-2 spike protein amino acid sequence of the Delta and Omicron variants in Thailand were retrieved from GIDSAID to determine mutation frequencies and to identify possible roles of the mutations based on published data.

RESULTS: Data was collected from a total of 247 participants comprising 106 and 141 participants of the Delta and Omicron epidemic periods, respectively. Apart from the COVID-19 severity and health status, the baseline participant data of the two time periods were remarkably similar. The prevalence of long COVID observed in the Omicron period was higher than in the Delta period (74.5% vs. 66.0%). The biological factors associated with long COVID were epidemic variant, age, treatment with symptomatic medicines, and vaccination status. When the spike protein sequence data of the two variants were compared, it was observed that the Omicron variant exhibited a greater quantity of amino acid changes in its receptor-binding domain (RBD) and receptor-binding motif (RBM). The critical changes of the Omicron variant within these regions had a significant function in enhancing virus transmissibility and host immune response resistance.

CONCLUSION: This study revealed informative data associated with long COVID in Thailand. More attention should be given to long COVID caused by unique virus variants and other biological factors to prepare a healthcare management strategy for COVID-19 patients after recovery.}, } @article {pmid39175159, year = {2024}, author = {Milne, A and Arnold, D and Moore, A}, title = {Understanding post-hospitalised patients' experiences of long-COVID - the PELCO study.}, journal = {Journal of health psychology}, volume = {}, number = {}, pages = {13591053241272233}, doi = {10.1177/13591053241272233}, pmid = {39175159}, issn = {1461-7277}, abstract = {Despite significant advances in long COVID research, many aspects of the condition remain unknown. There is a persisting need for further research to improve the management of long COVID symptoms. This study aimed to explore the experiences and psychological needs of patients who were previously hospitalised with COVID-19, and who subsequently developed long COVID symptoms. Twelve patients with long COVID were interviewed between October 2021 and June 2022. Transcripts were analysed thematically. An overarching theme of 'Existential Crisis' was developed, incorporating three interconnecting sub-themes: 'Facing Psychological Threat', 'Seeking Legitimisation' and 'Forging a Path Through Uncertainty'. Findings suggest that the psychological impact of emergency hospitalisation for COVID-19 can be severe, particularly for those with ongoing long COVID symptoms, and that early psychological intervention should be available. Our findings also suggest the importance of further planning for future pandemics to ensure the presence of patient advocates during hospitalisation at points of critical decision-making.}, } @article {pmid39172652, year = {2024}, author = {Ghorra, N and Popotas, A and Besse-Hammer, T and Rogiers, A and Corazza, F and Nagant, C}, title = {Cytokine Profile in Patients with Postacute Sequelae of COVID-19.}, journal = {Viral immunology}, volume = {37}, number = {7}, pages = {346-354}, doi = {10.1089/vim.2024.0025}, pmid = {39172652}, issn = {1557-8976}, mesh = {Humans ; *COVID-19/immunology/blood ; *Cytokines/blood ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Cytokine Release Syndrome/blood/immunology ; Toll-Like Receptors/blood ; Toll-Like Receptor 4/blood ; }, abstract = {The enduring impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease manifestation, COVID-19, on public health remains significant. Postacute sequelae of SARS-CoV-2 infection (PASC) affect a considerable number of patients, impairing their quality of life. While the role of the cytokine storm in acute COVID-19 is well established, its contribution to the pathophysiology of PASC is not fully understood. This study aimed to analyze the cytokine profile of patients with PASC following in vitro stimulation of Toll-like receptor (TLR) pathways, comparing them with a healthy control group. From October 2020 till March 2021, Brugmann University Hospital's clinical research unit included patients with PASC in the study. Whole blood samples were collected from 50 patients and 25 healthy volunteers. After in vitro stimulation under five different conditions, cytokine levels were measured using a multiplex method. Significantly decreased cytokine levels were observed in patients with PASC compared with healthy volunteers, particularly after TLR4 (interleukin [IL]-1α, IL-1β, IL-2, IL-10, interferon (IFN)α, IFNγ, IFNω, and tumor necrosis factor (TNF)α) and TLR7/8 (IL-1α, IL-1β, IFNα, IFNω, IFNγ, and TNFα) pathway stimulation. Principal component analysis identified two distinct clusters, suggesting a likely dysregulation of immunity involving TLR4 and TLR7/8 pathways in patients with PASC. Our study suggests that TLR4 and TLR7/8 pathways play a role in the pathophysiology of PASC. Continuous basal activation of immunity could explain the high basal concentrations of cytokines described in these patients and the decreased amplitude of response of these signaling pathways following specific stimulation.}, } @article {pmid39172559, year = {2024}, author = {Tajer, C and Martínez, MJ and Straw, C and Tajer, D and Riveiro, M and Antonietti, L}, title = {Analysis of long COVID in health personnel: comparing gender and work factors.}, journal = {Medicina}, volume = {84}, number = {4}, pages = {605-618}, pmid = {39172559}, issn = {1669-9106}, mesh = {Humans ; Female ; Cross-Sectional Studies ; Male ; *COVID-19/epidemiology ; *Health Personnel/statistics & numerical data ; Adult ; Sex Factors ; Argentina/epidemiology ; Middle Aged ; Prevalence ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: This study aimed to describe the reported prevalence of post-COVID-19 syndrome and its characteristics by gender, profession, and other determinants among health care workers.

METHODS: A cross-sectional study was conducted among health workers with a history of COVID-19 in Latin America, and the 2030 responses from Argentina were selected for this analysis. Sociodemographic information, as well as data on initial course of COVID-19, and the persistence of 21 symptoms beyond the first month, their severity, clinical evolution, and health care demands were collected.

RESULTS: The reported prevalence of post-COVID-19 syndrome was higher in women for each of the symptom clusters studied. Severity of the initial symptoms, female gender, nursing profession, multi-employment, and working in emergency areas were all independent variables.

DISCUSSION: The greater strain of health care workers during the pandemic -highly feminized- and the associated gender conditions may partially explain these findings.}, } @article {pmid39172356, year = {2024}, author = {Hill, MJ and Huebinger, RM and Ebna Mannan, I and Yu, H and Wisk, LE and O'Laughlin, KN and Gentile, NL and Stephens, KA and Gottlieb, M and Weinstein, RA and Koo, K and Santangelo, M and Saydah, S and Spatz, ES and Lin, Z and Schaeffer, K and Kean, E and Montoy, JCC and Rodriguez, RM and Idris, AH and McDonald, S and Elmore, JG and Venkatesh, A}, title = {Race, Ethnicity, and Gender Differences in Patient Reported Well-Being and Cognitive Functioning Within 3 Months of Symptomatic Illness During COVID-19 Pandemic.}, journal = {Journal of racial and ethnic health disparities}, volume = {}, number = {}, pages = {}, pmid = {39172356}, issn = {2196-8837}, abstract = {BACKGROUND: Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being.

METHODS: This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3 months and change in outcomes from baseline to 3 months among groups with different races, ethnicities, and/or sexes.

RESULTS: Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3 months and experienced more improvement in fatigue over 3 months (- 2.7 [- 4.7, - 0.8]). At 3 months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3 months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference.

CONCLUSIONS: Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.}, } @article {pmid39171285, year = {2023}, author = {Liu, Y and Gu, X and Li, H and Zhang, H and Xu, J}, title = {Mechanisms of long COVID: An updated review.}, journal = {Chinese medical journal pulmonary and critical care medicine}, volume = {1}, number = {4}, pages = {231-240}, pmid = {39171285}, issn = {2772-5588}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 3 years, with an enormous impact on global health and economies. In some patients, symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which cannot be explained by an alternate diagnosis; this condition has been defined as long COVID. Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants. The most common symptoms include fatigue, dyspnea, and other symptoms involving multiple organs. Vaccination results in lower rates of long COVID. To date, the mechanisms of long COVID remain unclear. In this narrative review, we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.}, } @article {pmid39170602, year = {2024}, author = {Yin, Y and Yang, G and Wang, N and Zeng, M and Jiang, H and Yuan, S and Wu, J and Zhang, J and Cui, J and Zhou, G and Yang, X and Zhang, Y and Sun, Z and Yuan, J and Lin, J and Chen, J and Tang, M and Chen, J}, title = {Exploring the prevalence and chest CT predictors of Long COVID in children: a comprehensive study from Shanghai and Linyi.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1420196}, pmid = {39170602}, issn = {2296-2360}, abstract = {INTRODUCTION: COVID-19 constitutes a pandemic of significant detriment to human health. This study aimed to investigate the prevalence of Long COVID following SARS-CoV-2 infection, analyze the potential predictors of chest CT for the development of Long COVID in children.

METHODS: A cohort of children who visited the respiratory outpatient clinics at Shanghai Children's Medical Center or Linyi Maternal and Child Health Care Hospital from December 2022 to February 2023 and underwent chest CT scans within 1 week was followed up. Data on clinical characteristics, Long COVID symptoms, and chest CT manifestations were collected and analyzed. Multivariate logistic regression models and decision tree models were employed to identify factors associated with Long COVID.

RESULTS: A total of 416 children were included in the study. Among 277 children who completed the follow-up, the prevalence of Long COVID was 23.1%. Chronic cough, fatigue, brain fog, and post-exertional malaise were the most commonly reported symptoms. In the decision tree model for Long COVID, the presence of increased vascular markings, the absence of normal CT findings, and younger age were identified as predictors associated with a higher likelihood of developing Long COVID in children. However, no significant correlation was found between chest CT abnormality and the occurrence of Long COVID.

DISCUSSION: Long COVID in children presents a complex challenge with a significant prevalence rate of 23.1%. Chest CT scans of children post-SARS-CoV-2 infection, identified as abnormal with increased vascular markings, indicate a higher risk of developing Long COVID.}, } @article {pmid39169314, year = {2024}, author = {Sprague Martinez, L and Sharma, N and John, J and Battaglia, TA and Linas, BP and Clark, CR and Hudson, LB and Lobb, R and Betz, G and Ojala O'Neill, SO and Lima, A and Doty, R and Rahman, S and Bassett, IV}, title = {Long COVID impacts: the voices and views of diverse Black and Latinx residents in Massachusetts.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2265}, pmid = {39169314}, issn = {1471-2458}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/psychology ; *COVID-19/ethnology/psychology ; Focus Groups ; *Hispanic or Latino/psychology ; Massachusetts ; *Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To understand how Long COVID is impacting the health and social conditions of the Black and Latinx communities.

BACKGROUND: Emerging research on Long COVID has identified three distinct characteristics, including multi-organ damage, persistent symptoms, and post-hospitalization complications. Given Black and Latinx communities experienced significantly higher COVID rates in the first phase of the pandemic they may be disproportionately impacted by Long COVID.

METHODS: Eleven focus groups were conducted in four languages with diverse Black and Latinx individuals (n = 99) experiencing prolonged symptoms of COVID-19 or caring for family members with prolonged COVID-19 symptoms. Data was analyzed thematically.

RESULTS: Most participants in non-English language groups reported they were unfamiliar with the diagnosis of long COVID, despite experiencing symptoms. Long COVID impacts spanned financial and housing stability to physical and mental health impacts. Participants reported challenging encounters with health care providers, a lack of support managing symptoms and difficulty performing activities of daily living including work.

CONCLUSIONS: There is a need for multilingual, accessible information about Long COVID symptoms, improved outreach and healthcare delivery, and increased ease of enrollment in long-term disability and economic support programs.}, } @article {pmid39167485, year = {2024}, author = {Rao, S}, title = {Uncovering Long COVID in Children.}, journal = {JAMA}, volume = {}, number = {}, pages = {}, doi = {10.1001/jama.2024.13551}, pmid = {39167485}, issn = {1538-3598}, } @article {pmid39164752, year = {2024}, author = {Calzari, L and Dragani, DF and Zanotti, L and Inglese, E and Danesi, R and Cavagnola, R and Brusati, A and Ranucci, F and Di Blasio, AM and Persani, L and Campi, I and De Martino, S and Farsetti, A and Barbi, V and Gottardi Zamperla, M and Baldrighi, GN and Gaetano, C and Parati, G and Gentilini, D}, title = {Epigenetic patterns, accelerated biological aging, and enhanced epigenetic drift detected 6 months following COVID-19 infection: insights from a genome-wide DNA methylation study.}, journal = {Clinical epigenetics}, volume = {16}, number = {1}, pages = {112}, pmid = {39164752}, issn = {1868-7083}, support = {RCR-2020-23670065//Ricerca Corrente Reti 2020/ ; RCR-2020-23670065//Ricerca Corrente Reti 2020/ ; RCR-2020-23670065//Ricerca Corrente Reti 2020/ ; RCR-2020-23670065//Ricerca Corrente Reti 2020/ ; RCR-2021-23671212//Ricerca Corrente Reti 2021/ ; RCR-2021-23671212//Ricerca Corrente Reti 2021/ ; RCR-2021-23671212//Ricerca Corrente Reti 2021/ ; RCR-2021-23671212//Ricerca Corrente Reti 2021/ ; }, mesh = {Humans ; *DNA Methylation/genetics ; *COVID-19/genetics ; *Epigenesis, Genetic/genetics ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; *CpG Islands/genetics ; Adult ; Aging/genetics ; Aged ; Genome-Wide Association Study/methods ; Post-Acute COVID-19 Syndrome ; Italy ; }, abstract = {BACKGROUND: The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. The existence of long-COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless of initial infection severity. The mechanisms behind long-COVID are unclear, but virus-induced epigenetic changes could play a role.

METHODS AND RESULTS: Our study explores the lasting epigenetic impacts of SARS-CoV-2 infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort of 96 patients 6 months after COVID-19 exposure, comparing them to 191 healthy controls. We identified 42 CpG sites with significant methylation differences (FDR < 0.05), primarily within CpG islands and gene promoters. Dysregulated genes highlighted potential links to glutamate/glutamine metabolism, which may be relevant to PASC symptoms. Key genes with potential significance to COVID-19 infection and long-term effects include GLUD1, ATP1A3, and ARRB2. Furthermore, Horvath's epigenetic clock showed a slight but significant age acceleration in post-COVID-19 patients. We also observed a substantial increase in stochastic epigenetic mutations (SEMs) in the post-COVID-19 group, implying potential epigenetic drift. SEM analysis identified 790 affected genes, indicating dysregulation in pathways related to insulin resistance, VEGF signaling, apoptosis, hypoxia response, T-cell activation, and endothelin signaling.

CONCLUSIONS: Our study provides valuable insights into the epigenetic consequences of COVID-19. Results suggest possible associations with accelerated aging, epigenetic drift, and the disruption of critical biological pathways linked to insulin resistance, immune response, and vascular health. Understanding these epigenetic changes could be crucial for elucidating the complex mechanisms behind long-COVID and developing targeted therapeutic interventions.}, } @article {pmid39164284, year = {2024}, author = {Palmer, CS and Perdios, C and Abdel-Mohsen, M and Mudd, J and Datta, PK and Maness, NJ and Lehmicke, G and Golden, N and Hellmers, L and Coyne, C and Moore Green, K and Midkiff, C and Williams, K and Tiburcio, R and Fahlberg, M and Boykin, K and Kenway, C and Russell-Lodrigue, K and Birnbaum, A and Bohm, R and Blair, R and Dufour, JP and Fischer, T and Saied, AA and Rappaport, J}, title = {Non-human primate model of long-COVID identifies immune associates of hyperglycemia.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6664}, pmid = {39164284}, issn = {2041-1723}, support = {P51OD011104//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 75N95020D00007/DA/NIDA NIH HHS/United States ; R01 DK123733/DK/NIDDK NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; 3P51OD011104-61S1//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; R01 NS117458/NS/NINDS NIH HHS/United States ; 75N98020D00007/NH/NIH HHS/United States ; R01 AI165079/AI/NIAID NIH HHS/United States ; UC7 AI180314/AI/NIAID NIH HHS/United States ; S10 OD026800/OD/NIH HHS/United States ; R01 DE032291/DE/NIDCR NIH HHS/United States ; R01 AA029859/AA/NIAAA NIH HHS/United States ; 75N99020D00007/OF/ORFDO NIH HHS/United States ; 75N94020D00007/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Hyperglycemia/immunology ; *COVID-19/immunology/virology/blood ; *Disease Models, Animal ; Chlorocebus aethiops ; *SARS-CoV-2/immunology ; *Liver/virology/metabolism/immunology ; Glycogen/metabolism ; Blood Glucose/metabolism ; Humans ; Male ; Pancreas/virology/immunology/pathology/metabolism ; Chemokines/metabolism/blood ; Female ; Virus Replication ; }, abstract = {Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.}, } @article {pmid39163793, year = {2024}, author = {Munipalli, B and Smith, A and Baird, AR and Dobrowolski, CS and Allman, ME and Thomas, LG and Bruce, BK}, title = {A description of the development of an innovative multi-component long COVID treatment program based on central sensitization with preliminary patient satisfaction data.}, journal = {Journal of psychosomatic research}, volume = {185}, number = {}, pages = {111884}, doi = {10.1016/j.jpsychores.2024.111884}, pmid = {39163793}, issn = {1879-1360}, mesh = {Humans ; *COVID-19/psychology/therapy ; Female ; Male ; *Patient Satisfaction ; Middle Aged ; Cross-Sectional Studies ; Adult ; *Depression/therapy/psychology ; *Cognitive Behavioral Therapy/methods ; Aged ; Central Nervous System Sensitization ; Catastrophization/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Estimates of the prevalence of Long COVID in the United States or worldwide are imprecise, but millions of people are thought to be affected. No effective treatment exists for the often devastating symptoms of Long COVID. Central Sensitization has been postulated as a causal/explanatory mechanism for developing Long COVID. No treatment to date has targeted Central Sensitization. The present cross-sectional study describes the first 140 patients treated in a multi-component treatment program that targets Central Sensitization to reduce symptom burden, improve functioning, and lower the psychological distress observed in these patients.

METHODS: 140 patients diagnosed with Long COVID after an extensive medical evaluation were assessed for function, depression, and pain catastrophizing using questionnaires and patient satisfaction measures after completion of a 16-h Cognitive Behavioral Therapy treatment program focused on Central Sensitization.

RESULTS: Upon admission, patients diagnosed with Long COVID were significantly impaired in their ability to function due to their symptoms. Further, 70% of the patients were depressed. Pain catastrophizing was observed in up to 20% of patients.

CONCLUSION: Patient satisfaction measures were high for the sample at the end of the treatment program suggesting that a multicomponent treatment program targeting Central Sensitization is acceptable to patients. Further research is needed to explore the effectiveness and durability of this treatment approach.}, } @article {pmid39163767, year = {2024}, author = {Vlaming-van Eijk, LE and Bulthuis, MLC and van der Gun, BTF and Wold, KI and Veloo, ACM and Vincenti González, MF and de Borst, MH and den Dunnen, WFA and Hillebrands, JL and van Goor, H and Tami, A and Bourgonje, AR}, title = {Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals.}, journal = {Redox biology}, volume = {76}, number = {}, pages = {103310}, pmid = {39163767}, issn = {2213-2317}, mesh = {Humans ; *Oxidative Stress ; *COVID-19/blood/complications/virology ; Female ; Male ; Middle Aged ; *SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; Sulfhydryl Compounds/blood ; Aged ; Biomarkers/blood ; Longitudinal Studies ; }, abstract = {BACKGROUND: Post-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R-SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R-SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19.

METHODS: Baseline serum R-SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R-SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS.

RESULTS: Baseline albumin-adjusted serum R-SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R-SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = -9.48, p = 0.023).

CONCLUSION: Non-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R-SH as a monitoring biomarker and a potential therapeutic target in the development of PCS.}, } @article {pmid39163143, year = {2025}, author = {Gómez-Carballa, A and Pischedda, S and Pardo-Seco, J and Gómez-Rial, J and Martinón-Torres, F and Salas, A}, title = {Interferon gene expression declines over time post-COVID infection and in long COVID patients.}, journal = {Infectious diseases (London, England)}, volume = {57}, number = {1}, pages = {35-48}, doi = {10.1080/23744235.2024.2389481}, pmid = {39163143}, issn = {2374-4243}, mesh = {Humans ; *COVID-19/genetics ; *Interferons ; Female ; Male ; Middle Aged ; *SARS-CoV-2/genetics ; Cohort Studies ; Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Autoimmune Diseases/genetics ; Gene Expression ; }, abstract = {BACKGROUND: Interferons (IFNs) represent a first-line defense against viruses and other pathogens. It has been shown that an impaired and uncontrolled release of these glycoproteins can result in tissue damage and explain severe progression of coronavirus disease 2019 (COVID-19). However, their potential role in Long-COVID syndrome (LC) remains debateable.

OBJECTIVES: The objective of the present study is to shed further light on the possible role of IFNs (and related genes) gene expression patterns in the progression of COVID-19 and LC patients.

METHODS: We carried out a multi-cohort study by analyzing the IFN gene expression patterns (using different IFN gene signatures) in five cohorts of acute COVID-19 (n = 541 samples) and LC patients (n = 188), and compared them to patterns observed in three autoimmune diseases (systemic lupus erythematous [n = 242], systemic sclerosis [n = 91], and Sjögren's syndrome [n = 282]).

RESULTS: The data show that, while the interferon signatures are strongly upregulated in severe COVID-19 patients and autoimmune diseases, it decays with the time from symptoms onset and in LC patients. Differential pathway analysis of IFN-related terms indicates an over activation in autoimmune diseases (IFN-I/II) and severe COVID-19 (IFN-I/II/III), while these pathways are mostly inactivated or downregulated in LC (IFN-I/III). By analyzing six proteomic LC datasets, we did not find evidence of a role of IFNs in this condition.

CONCLUSION: Our findings suggest a potential role of cytokine exhaustion mediated by IFN gene expression inactivation as a possible driver of LC.}, } @article {pmid39162988, year = {2024}, author = {Farrell, A and O'Flynn, J and Jennings, A}, title = {An investigation into General Practitioners' experience with Long Covid.}, journal = {Irish journal of medical science}, volume = {193}, number = {6}, pages = {2869-2873}, pmid = {39162988}, issn = {1863-4362}, mesh = {Humans ; *General Practitioners/statistics & numerical data ; *COVID-19 ; Ireland ; Surveys and Questionnaires ; Female ; Male ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Attitude of Health Personnel ; Referral and Consultation/statistics & numerical data ; Adult ; Clinical Competence/statistics & numerical data ; Middle Aged ; }, abstract = {BACKGROUND: Long Covid (LC) is the continuation or development of new symptoms after initial COVID-19 infection. Little is known about General Practitioners' (GP) experience of managing patients with LC.

AIMS: The aim of this study is to establish GP experiences with LC.

METHODS: A survey was designed and piloted in three training practices prior to distribution. The survey was completed by doctors working in GP training scheme practices in Cork, Ireland.

RESULTS: Fifty-three of one hundred and sixty invited GPs completed the survey, indicating a 33% response rate. 8% (4/53) of participants agreed and 0% (0/53) strongly agreed with the statement they were "confident in diagnosing Long Covid". 81% (43/53) were not confident in treating patients with LC. 70% (37/53) were unaware of indications for referral to secondary care. 38% (20/53) were aware of the referral pathways to local LC clinics. 93% (49/53) agreed there were educational deficits regarding LC.

CONCLUSIONS: There was a lack of confidence in the diagnosis and management of LC, and in the interface with secondary care. There is demand for educational interventions to assist GPs with their care of patients with this emerging condition.}, } @article {pmid39161542, year = {2024}, author = {Maher, A and Bennett, M and Huang, HC and Gaughwin, P and Johnson, M and Brady, M and Patterson, K and Buettikofer, T and Morris, J and Rainbird, VM and Mitchell, I and Bissett, B}, title = {Personalized Exercise Prescription in Long COVID: A Practical Toolbox for a Multidisciplinary Approach.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {3981-3991}, pmid = {39161542}, issn = {1178-2390}, abstract = {OBJECTIVE: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature.

BACKGROUND: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia's few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation.

METHODS: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer's presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4-6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual's progress, at an intensity 4-6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥50% of their maximum inspiratory pressure).

DISCUSSION: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts.

CONCLUSION: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual's symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.}, } @article {pmid39159783, year = {2024}, author = {Cox, ER and Plotnikoff, RC and Gibson, PG and Keating, SE and Acharya, S and Lewthwaite, H}, title = {Prevalence of Long COVID and the Impact on Diabetes Management and Physical Activity Participation in Adults With Type 2 Diabetes: An Australia-wide Cross-sectional Online Survey.}, journal = {Canadian journal of diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcjd.2024.08.004}, pmid = {39159783}, issn = {2352-3840}, abstract = {OBJECTIVES: The aim of this research was to understand the prevalence and impact of long COVID on adults with type 2 diabetes (T2D). Specifically, we sought to identify the proportion of adults with T2D who have had COVID-19 and experienced long COVID symptoms. We also explored how these ongoing symptoms impact diabetes management and physical activity participation.

METHODS: Our study was carried out using an online survey of adults in Australia with T2D who had confirmed COVID-19 ≥12 weeks before participation. Respondents were asked to report the presence (and severity) of long COVID-19 symptoms, and, for those with long COVID, the impact of their symptoms on diabetes management (blood glucose, body weight) and physical activity participation (activities of daily living, work/study, exercise).

RESULTS: Survey responses were provided by 1,046 adults with T2D (median age 61.0 [interquartile range 49.8 to 70.0] years; 56.0% men, 42.1% women, and 1% nonbinary/transgender; median T2D duration 10.0 [5.0 to 18.0] years and median time since COVID-19 infection 33.0 [20.3 to 36.1] weeks). Almost one third (30%) of respondents reported long COVID symptoms (present ≥12 weeks after most recent infection); 40% of respondents with long COVID symptoms reported a worsening of their diabetes management since their COVID-19 infection, with 29% reporting trouble controlling their blood glucose and 43% reporting a higher body weight. Two thirds of respondents with ongoing symptoms reported that these symptoms moderately to severely impacted their ability to perform activities of daily living, work, and/or exercise. The majority of those with long COVID reported reducing the frequency, duration, and/or intensity of exercise since their COVID-19 infection, with 36.1% not yet returning to their preinfection exercise levels; 66% cited ongoing symptoms as the primary reason for these limitations.

CONCLUSIONS: Physical activity is a crucial component of diabetes management. However, the high prevalence of long COVID is hindering participation in this population, as well as deleteriously impacting diabetes management. Developing strategies to support adults with T2D and long COVID to recommence safe levels of physical activity is of critical importance.}, } @article {pmid39159607, year = {2024}, author = {Gorenshtein, A and Leibovitch, L and Liba, T and Stern, S and Stern, Y}, title = {Gender Disparities in Neurological Symptoms of Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Neuroepidemiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1159/000540919}, pmid = {39159607}, issn = {1423-0208}, abstract = {BACKGROUND: Female gender is a known risk factor for long COVID. With the increasing number of COVID-19 cases, the corresponding number of survivors is also expected to rise. To the best of our knowledge, no systematic review has specifically addressed the gender differences in neurological symptoms of long COVID.

METHODS: We included studies on female individuals who presented with specific neurological symptoms at least 12 weeks after confirmed COVID-19 diagnosis from PubMed, Central, Scopus, and Web of Science. The search limit was put for after January 2020 until June 15, 2024. We excluded studies that did not provide sex-specific outcome data, those not in English, case reports, case series, and review articles Results: A total of 5,632 eligible articles were identified. This article provides relevant information from 12 studies involving 6,849 patients, of which 3,414 were female. The sample size ranged from 70 to 2,856, with a maximum follow-up period of 18 months. The earliest publication date was September 16, 2021, while the latest was June 11, 2024. The following neurological symptoms had a significant difference in the risk ratio (RR) for female gender: fatigue RR 1.40 (95% confidence interval [CI]: 1.22-1.60, p < 0.001), headache RR 1.37 (95% CI: 1.12-1.67, p = 0.002), brain-fog RR 1.38 (95% CI 1.08-1.76, p = 0.011) depression RR 1.49 (95% CI: 1.2-1.86, p < 0.001), and anosmia RR 1.61 (95% CI: 1.36-1.90, p < 0.001). High heterogenicity was found for fatigue, brain fog, and anxiety due to the diverse methodologies employed in the studies.

CONCLUSION: Our findings suggest that women are at a higher risk for long-COVID neurological symptoms, including fatigue, headaches, brain fog, depression, and anosmia, compared to men. The prevalence of these symptoms decreases after 1 year, based on limited data from the small number of studies available beyond this period.}, } @article {pmid39159474, year = {2024}, author = {Oaklander, AL}, title = {Increasing associations of long-COVID with small-fiber neuropathy.}, journal = {Pain}, volume = {165}, number = {9}, pages = {e93-e95}, pmid = {39159474}, issn = {1872-6623}, support = {R01 NS093653/NS/NINDS NIH HHS/United States ; U01 FD007769/FD/FDA HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Small Fiber Neuropathy/physiopathology/diagnosis ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid39159462, year = {2024}, author = {}, title = {Correction: Long COVID Definitions and Models of Care.}, journal = {Annals of internal medicine}, volume = {177}, number = {9}, pages = {1294-1295}, doi = {10.7326/ANNALS-24-01431}, pmid = {39159462}, issn = {1539-3704}, } @article {pmid39158581, year = {2024}, author = {Boscolo-Rizzo, P and Hummel, T and Menini, A and Maniaci, A and Uderzo, F and Bigolin, L and Tirelli, G}, title = {Adherence to olfactory training improves orthonasal and retronasal olfaction in post-COVID-19 olfactory loss.}, journal = {Rhinology}, volume = {62}, number = {6}, pages = {681-688}, doi = {10.4193/Rhin24.233}, pmid = {39158581}, issn = {0300-0729}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Male ; Female ; *Olfaction Disorders/rehabilitation/physiopathology/etiology/virology ; Prospective Studies ; Middle Aged ; Smell/physiology ; SARS-CoV-2 ; Aged ; Adult ; Patient Compliance ; Olfactory Training ; }, abstract = {BACKGROUND: Olfactory loss (OL) has emerged as one of the most prevalent and debilitating symptoms of SARS-CoV-2 infection and long-COVID-19. The present prospective observational study aimed to evaluate the efficacy of olfactory training (OT) on orthonasal and retronasal olfactory function in a cohort of individuals with persistent post-COVID-19 OL.

METHODOLOGY: Participants with post-COVID-19 olfactory impairment underwent 4 months of OT, self-assessing their smell perception and undergoing comprehensive psychophysical evaluation of orthonasal and retronasal olfaction at baseline and after training. Orthonasal olfactory function was assessed using the extended Sniffin' Sticks test battery. Retronasal olfactory function was tested with powdered aromas.

RESULTS: Among 114 participants with post-COVID-19 olfactory loss, adherence to OT was 60%. In adherents, the average increase in composite TDI score was 6.0 points compared to 2.6 points in non-adherents. Fifty-seven percent of adherent participants achieved a clinically significant improvement in TDI score (≥ 5.5 points), compared to 22% of non-adherents. In retronasal olfactoryidentification, 56% of adherents achieved a clinically significant improvement (≥ 4 points), compared to 16% of non-adherents.

CONCLUSION: Adherence to a 4-month OT regimen can yield clinically meaningful improvements in both orthonasal and retronasal olfactory function among individuals with persistent post-COVID-19 olfactory dysfunction.}, } @article {pmid39158051, year = {2024}, author = {Maes, M and Almulla, AF and Tang, X and Stoyanova, K and Vojdani, A}, title = {From human herpes virus-6 reactivation to autoimmune reactivity against tight junctions and neuronal antigens, to inflammation, depression, and chronic fatigue syndrome due to Long COVID.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29864}, doi = {10.1002/jmv.29864}, pmid = {39158051}, issn = {1096-9071}, support = {HEA663000016//Thailand Science Research, and Innovation Fund/ ; 64.310/436/2565//Chulalongkorn University/ ; RA66/016//Sompoch Endowment Fund (Faculty of Medicine) MDCU/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/immunology/virology ; *Herpesvirus 6, Human/immunology ; Female ; Male ; Middle Aged ; *Tight Junctions/immunology ; *COVID-19/immunology ; *Autoimmunity ; *Inflammation/immunology ; Adult ; Occludin ; Depression/immunology ; SARS-CoV-2/immunology ; Aged ; Immunoglobulin G/blood ; Post-Acute COVID-19 Syndrome ; Immunoglobulin A/blood ; Lipopolysaccharides/immunology ; Autoantibodies/blood/immunology ; Antibodies, Viral/blood ; Roseolovirus Infections/immunology/complications/virology ; Haptoglobins ; Protein Precursors ; }, abstract = {Inflammation and autoimmune responses contribute to the pathophysiology of Long COVID, and its affective and chronic fatigue syndrome symptoms, labeled "the physio-affective phenome." To investigate whether Long COVID and its physio-affective phenome are linked to autoimmunity to the tight junction proteins, zonulin and occludin (ZOOC), and immune reactivity to lipopolysaccharides (LPS), and whether the latter are associated with signs of human herpes virus-6 (HHV-6) reactivation, autoimmunity directed against oligodendrocyte and neuronal proteins, including myelin basic protein. IgA/IgM/IgG responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HHV-6, ZOOC, and neuronal proteins, C-reactive protein (CRP), and advanced oxidation protein products (AOPPs), were measured in 90 Long COVID patients and 90 healthy controls. The physio-affective phenome was conceptualized as a factor extracted from physical and affective symptom domains. Neural network identified IgA directed to LPS (IgA-LPS), IgG-ZOOC, IgG-LPS, and IgA-ZOOC as important variables associated with Long COVID diagnosis with an area under the ROC curve of 0.755. Partial Least Squares analysis showed that 40.9% of the variance in the physio-affective phenome was explained by CRP, IgA-myelin basic protein (MBP), and IgG-MBP. A large part of the variances in both autoimmune responses to MBP (36.3%-39.7%) was explained by autoimmunity (IgA and IgG) directed to ZOOC. The latter was strongly associated with indicants of HHV-6 reactivation, which in turn was associated with increased IgM-SARS-CoV-2. Autoimmunity against components of the tight junctions and increased bacterial translocation may be involved in the pathophysiology of Long COVID's physio-affective phenome.}, } @article {pmid39155763, year = {2024}, author = {Kaya, Ç and Yalta, K}, title = {Is Constrictive Pericarditis Associated with Long COVID, Its Vaccine, or Both?.}, journal = {Balkan medical journal}, volume = {41}, number = {5}, pages = {411-412}, pmid = {39155763}, issn = {2146-3131}, mesh = {Humans ; *Pericarditis, Constrictive/etiology ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; Male ; }, } @article {pmid39154907, year = {2024}, author = {Tavee, J}, title = {Current concepts in long COVID-19 brain fog and postural orthostatic tachycardia syndrome.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {133}, number = {5}, pages = {522-530}, doi = {10.1016/j.anai.2024.08.008}, pmid = {39154907}, issn = {1534-4436}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/physiopathology/therapy ; *COVID-19/complications/physiopathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Cognitive Dysfunction/etiology/physiopathology ; Quality of Life ; Cognitive Behavioral Therapy ; }, abstract = {Neurologic complications of long COVID-19 syndrome are one of the leading causes of global disability. In particular, post-COVID-19 cognitive dysfunction and dysautonomia in the form of postural orthostatic tachycardia syndrome (POTS) markedly affect patient quality of life and ability to return to work. The underlying pathophysiology of post-COVID-19 neurologic complications is unknown but is likely multifactorial with immune dysregulation and microvascular dysfunction playing central roles. Specific pathogenic factors with supportive evidence to date include cytokine-mediated inflammation, autoantibodies, immune exhaustion, disruption of the renin-angiotensin system, reduced serotonin levels, and microglial activation. The prevalence of post-COVID-19 cognitive dysfunction ranges from 10% to 88% and is affected by viral variant and hospitalization status among other factors, whereas that of long COVID-19 POTS is unknown due to referral bias and varying definitions. Treatment is largely supportive and often incorporates combined modalities. Marginal benefits with cognitive behavioral therapy, hyperbaric oxygen therapy, and supplements have been found for post-COVID-19 brain fog, whereas established POTS therapies aimed at improving venous return and reducing heart rate may reduce symptoms of long COVID-19 POTS. Although significant recovery has been noted for many cases of post-COVID-19 brain fog and POTS, prospective studies have revealed evidence of persistent symptoms and neurologic deficits a year after infection in some patients. Further studies that provide insight into the underlying pathophysiology of long COVID-19 are needed for development of target directed therapy.}, } @article {pmid39154330, year = {2024}, author = {Kupovits, TR}, title = {[Symptoms and options in rehabilitation of post-COVID-19 syndrome (long-COVID)].}, journal = {Orvosi hetilap}, volume = {165}, number = {33}, pages = {1266-1274}, doi = {10.1556/650.2024.33107}, pmid = {39154330}, issn = {1788-6120}, mesh = {Humans ; Pandemics ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/rehabilitation/virology ; SARS-CoV-2 ; }, } @article {pmid39154292, year = {2024}, author = {Costantino, V and Grafton, Q and Kompas, T and Chu, L and Honeyman, D and Notaras, A and MacIntyre, CR}, title = {The public health and economic burden of long COVID in Australia, 2022-24: a modelling study.}, journal = {The Medical journal of Australia}, volume = {221}, number = {4}, pages = {217-223}, doi = {10.5694/mja2.52400}, pmid = {39154292}, issn = {1326-5377}, support = {#2016907//National Health and Medical Research Council/ ; //Balvi Filantropik fund/ ; }, mesh = {Humans ; Australia/epidemiology ; *COVID-19/epidemiology/economics ; Adult ; Middle Aged ; *Cost of Illness ; Child, Preschool ; Aged ; Child ; Adolescent ; Infant ; Young Adult ; Public Health/economics ; SARS-CoV-2 ; Gross Domestic Product ; Infant, Newborn ; Post-Acute COVID-19 Syndrome ; Female ; Male ; }, abstract = {OBJECTIVE: To estimate the number of people in Australia with long COVID by age group, and the associated medium term productivity and economic losses.

STUDY DESIGN: Modelling study: a susceptible-exposed-infected-recovered (SEIR) model to estimate the number of people with long COVID over time following single infections, and a labour supply model to estimate productivity losses as a proportion of gross domestic product (GDP).

SETTING: Australia, 2022-2024.

MAIN OUTCOME MEASURES: Estimated number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during 2022-2023 (based on serosurvey data) who have long COVID, 2022-2024, by age group; estimated GDP loss during 2022 caused by reduced labour supply attributable to long COVID.

RESULTS: Our model projected that the number of people with long COVID following a single infection in 2022 would peak in September 2022, when 310 341-1 374 805 people (1.2-5.4% of Australians) would have symptoms of long COVID, declining to 172 530-872 799 people (0.7-3.4%) in December 2024, including 7902-30 002 children aged 0-4 years (0.6-2.2%). The estimated mean labour loss attributable to long COVID in 2022 was projected to be 102.4 million (95% confidence interval [CI], 50.4-162.2 million) worked hours, equivalent to 0.48% (95% CI, 0.24-0.76%) of total worked hours in Australia during the 2020-21 financial year. The estimated mean GDP loss caused by the projected decline in labour supply and reduced use of other production factors was $9.6 billion (95% CI, $4.7-15.2 billion), or 0.5% of GDP. The estimated labour loss was greatest for people aged 30-39 years (27.5 million [95% CI, 16.0-41.0 million] hours; 26.9% of total labour loss) and people aged 40-49 years (24.5 million [95% CI, 12.1-38.7 million] hours; 23.9% of total labour loss).

CONCLUSION: Widespread SARS-CoV-2 infections in Australia mean that even a small proportion of infected people developing long COVID-related illness and disability could have important population health and economic effects. A paradigm shift is needed, from a sole focus on the immediate effects of coronavirus disease 2019 (COVID-19) to preventing and treating COVID-19 and treating long COVID, with implications for vaccine and antiviral policy and other mitigation of COVID-19.}, } @article {pmid39151826, year = {2024}, author = {Song, XD and Gao, HX and Tan, H and Xie, YY and Zhang, X and Zhang, CM and Wang, YL and Dai, EH}, title = {Prevalence of infection and reinfection among health care workers in a hospital of Northern China between BA.5/BF.7 and XBB.1.5 wave.}, journal = {American journal of infection control}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajic.2024.08.009}, pmid = {39151826}, issn = {1527-3296}, abstract = {BACKGROUND: To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs).

METHODS: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions.

RESULTS: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs.

CONCLUSIONS: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services.}, } @article {pmid39151680, year = {2024}, author = {Xu, J and Wu, D and Yang, J and Zhao, Y and Liu, X and Chang, Y and Tang, Y and Sun, F and Zhao, Y}, title = {Adult Outpatients with Long COVID Infected with SARS-CoV-2 Omicron Variant. Part 1: Oral Microbiota Alterations.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.07.030}, pmid = {39151680}, issn = {1555-7162}, abstract = {BACKGROUND: Many individuals experience long COVID after SARS-CoV-2 infection. As microbiota can influence health, it may change with COVID-19. This study investigated differences in oral microbiota between COVID-19 patients with and without long COVID.

METHODS: Based on a prospective follow-up investigation, this nested case-control study evaluated the differences in oral microbiota in individuals with and without long COVID (Symptomatic and Asymptomatic groups), which were assessed by 16S rRNA sequencing on tongue coating samples. A predictive model was established using machine learning based on specific differential microbial communities.

RESULTS: One-hundred-and-eight patients were included (n=54 Symptomatic group). The Symptomatic group had higher Alpha diversity indices (observed_otus, Chao1, Shannon, and Simpson indices), differences in microbial composition (Beta diversity), and microbial dysbiosis with increased diversity and relative abundance of pathogenic bacteria. Marker bacteria (c__Campylobacterota, o__Coriobacteriales, o__Pseudomonadales, and o__Campylobacterales) were associated with long COVID by linear discriminant analysis effect size and receiver operating characteristic curves (AUC 0.821).

CONCLUSION: There were distinct variations in oral microbiota between COVID-19 patients with and without long COVID. Changes in oral microbiota may indicate long COVID.}, } @article {pmid39151482, year = {2024}, author = {Salzano, A and Cittadini, A}, title = {Utility of cardiopulmonary exercise testing in the complexity of the long COVID syndrome. Novel findings from specific sub-groups of patients.}, journal = {International journal of cardiology}, volume = {415}, number = {}, pages = {132449}, doi = {10.1016/j.ijcard.2024.132449}, pmid = {39151482}, issn = {1874-1754}, mesh = {Humans ; *Exercise Test/methods ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; }, } @article {pmid39150750, year = {2024}, author = {El-Toukhy, S and Hegeman, P and Zuckerman, G and Das, AR and Moses, N and Troendle, J and Powell-Wiley, TM}, title = {Study of Postacute Sequelae of COVID-19 Using Digital Wearables: Protocol for a Prospective Longitudinal Observational Study.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e57382}, pmid = {39150750}, issn = {1929-0748}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Prospective Studies ; Longitudinal Studies ; Adult ; Male ; Middle Aged ; Female ; *Wearable Electronic Devices ; Aged ; Young Adult ; Post-Acute COVID-19 Syndrome ; Adolescent ; }, abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC) remain understudied in nonhospitalized patients. Digital wearables allow for a continuous collection of physiological parameters such as respiratory rate and oxygen saturation that have been predictive of disease trajectories in hospitalized patients.

OBJECTIVE: This protocol outlines the design and procedures of a prospective, longitudinal, observational study of PASC that aims to identify wearables-collected physiological parameters that are associated with PASC in patients with a positive diagnosis.

METHODS: This is a single-arm, prospective, observational study of a cohort of 550 patients, aged 18 to 65 years, male or female, who own a smartphone or a tablet that meets predetermined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a health care professional within 5 days before enrollment. The primary end point is long COVID-19, defined as ≥1 symptom at 3 weeks beyond the first symptom onset or positive diagnosis, whichever comes first. The secondary end point is chronic COVID-19, defined as ≥1 symptom at 12 weeks beyond the first symptom onset or positive diagnosis. Participants must be willing and able to consent to participate in the study and adhere to study procedures for 6 months.

RESULTS: The first patient was enrolled in October 2021. The estimated year for publishing the study results is 2025.

CONCLUSIONS: This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. The study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of the use of wearables as population-level monitoring health tools for communicable diseases.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04927442; https://clinicaltrials.gov/study/NCT04927442.

DERR1-10.2196/57382.}, } @article {pmid39150728, year = {2024}, author = {Anderer, S}, title = {Vaccines Lowered Risk of Long COVID in US Veterans, but Not Completely.}, journal = {JAMA}, volume = {332}, number = {10}, pages = {781}, doi = {10.1001/jama.2024.15518}, pmid = {39150728}, issn = {1538-3598}, } @article {pmid39150062, year = {2024}, author = {Gordon, JI and Brummel, NE}, title = {Implications of frailty before and after intensive care unit admission.}, journal = {Current opinion in critical care}, volume = {30}, number = {5}, pages = {472-478}, doi = {10.1097/MCC.0000000000001197}, pmid = {39150062}, issn = {1531-7072}, mesh = {Humans ; *COVID-19/epidemiology ; *Intensive Care Units ; *Frailty ; *Delirium ; *Critical Illness ; *SARS-CoV-2 ; Aged ; Frail Elderly ; Geriatric Assessment/methods ; }, abstract = {PURPOSE OF REVIEW: In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19.

RECENT FINDINGS: A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons.

SUMMARY: Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.}, } @article {pmid39146534, year = {2024}, author = {Butzin-Dozier, Z and Ji, Y and Li, H and Coyle, J and Shi, J and Phillips, RV and Mertens, AN and Pirracchio, R and van der Laan, MJ and Patel, RC and Colford, JM and Hubbard, AE and , }, title = {Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner: Cohort Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e53322}, pmid = {39146534}, issn = {2369-2960}, support = {U24 TR002306/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Cohort Studies ; Female ; Male ; United States/epidemiology ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; Adult ; Risk Factors ; Machine Learning ; }, abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited.

OBJECTIVE: Using a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States.

METHODS: We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites.

RESULTS: We were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis.

CONCLUSIONS: The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment.

RR2-10.1101/2023.07.27.23293272.}, } @article {pmid39146373, year = {2024}, author = {Su, H and Thompson, HJ and Figuracion, KC and Patel, MB and Needham, DM}, title = {Comparative analysis of financial toxicity between SARS-CoV-2 infection and common comorbidities.}, journal = {PloS one}, volume = {19}, number = {8}, pages = {e0309116}, pmid = {39146373}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/economics/epidemiology ; Male ; Female ; Middle Aged ; *Comorbidity ; Adult ; United States/epidemiology ; Cross-Sectional Studies ; Aged ; *SARS-CoV-2 ; Cost of Illness ; Young Adult ; Health Care Costs ; Post-Acute COVID-19 Syndrome ; Adolescent ; }, abstract = {Financial toxicity is common in individuals with COVID-19 and Long COVID. However, the extent of financial toxicity experienced, in comparison to other common comorbidities, is uncertain. Contributing factors exacerbating financial challenges in Long COVID are also unclear. These knowledge gaps are addressed via a cross-sectional analysis utilizing data from the 2022 National Health Interview Survey (NHIS), a representative sample drawn from the United States. COVID-19 cases were identified through self-reported positive testing or physician diagnoses. Long COVID was defined as experiencing COVID-19-related symptoms for more than three months. Comorbidity was assessed based on self-reported diagnoses of ten doctor-diagnosed conditions (Yes/No). Financial toxicity was defined as having difficulty paying medical bills, cost-related medication nonadherence, delaying healthcare due to cost, and/or not obtained healthcare due to cost. A total of 27,492 NHIS 2022 respondents were included in our analysis, representing 253 million U.S. adults. In multivariable logistic regression models, adults with Long COVID (excluding respondents with COVID-19 but not Long COVID), showed increased financial toxicity compared to those with other comorbidities, such as epilepsy (OR [95% CI]: 1.69 [1.22, 2.33]), dementia (1.51 [1.01, 2.25]), cancer (1.43 [1.19, 1.71]) or respiratory/cardiovascular conditions (1.18 [1.00, 1.40]/1.23 [1.02, 1.47]). Long COVID-related financial toxicity was associated with female sex, age <65 years, lack of medical insurance, current paid employment, residence region, food insecurity, fatigue, mild to severe depression symptoms experienced during the survey completion, visits to hospital emergency rooms, presence of arthritis, cardiovascular or respiratory conditions, and social activity limitations. In conclusion, American adults with Long COVID, but not those who had prior COVID-19 infection without Long COVID, exhibited a higher prevalence of financial toxicity compared to individuals with common comorbidities. Vulnerable populations were at greater risk for financial toxicity. These findings emphasize the importance of evaluating strategies to reduce economic burden and increase awareness of the effect of Long COVID-related financial toxicity on patient's healthcare and health status.}, } @article {pmid39145102, year = {2024}, author = {Haag, L and Richardson, J and Haig, C and Cunningham, Y and Fraser, H and Brosnahan, N and Ibbotson, T and Ormerod, J and White, C and McIntosh, E and O'Donnell, K and Sattar, N and McConnachie, A and Lean, M and Blane, D and Combet, E}, title = {Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT).}, journal = {NIHR open research}, volume = {4}, number = {}, pages = {7}, pmid = {39145102}, issn = {2633-4402}, abstract = {BACKGROUND: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC.

METHODS: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m [2]. The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention.

RESULTS: Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m [2] (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg).

CONCLUSIONS: Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented.

TRIAL REGISTRATION: ISRCTN registry (ISRCTN12595520, 25/11/2021).}, } @article {pmid39142509, year = {2024}, author = {Brode, WM and Melamed, E}, title = {A practical framework for Long COVID treatment in primary care.}, journal = {Life sciences}, volume = {354}, number = {}, pages = {122977}, doi = {10.1016/j.lfs.2024.122977}, pmid = {39142509}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *Primary Health Care ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; }, abstract = {Long COVID is a complex, multisystem illness with a poorly understood pathophysiology, absence of specific diagnostic tests or criteria, or evidence-based treatments. With over 200 identified symptoms and approximately 10% of COVID-19 cases resulting in Long COVID, it is a challenge to provide comprehensive treatment at a scale commensurate with the illness burden. The diverse manifestations of Long COVID, encompassing numerous medical specialties, typically place primary care providers (PCPs) at the forefront of management, navigating an evolving landscape of research and lack of evidence-based guidelines. This paper presents a pragmatic, structured framework for Long COVID management in primary care, integrating current knowledge and best practices. The approach is individualized, addressing Long COVID's broad symptomatology through a four-step framework. The first step focuses on energy management strategies, emphasizing the prevention of post-exertional malaise, a cardinal feature of Long COVID. The second step, intentional rehabilitation, employs carefully titrated multidisciplinary modalities to address physical, cognitive, and emotional domains. The third step utilizes symptomatic management through both pharmacological and non-pharmacological interventions, targeting debilitating symptoms like fatigue, insomnia, and chronic pain. The fourth step outlines an approach to trialing experimental, targeted therapies that may impact Long COVID's underlying pathophysiology. These treatments, while experimental and lacking quality evidence in Long COVID, may be available off-label on an individual basis following a thorough risk-benefit discussion. This stepwise framework can equip PCPs to effectively address the most common and disabling symptoms of Long COVID, individualize care, and remain attuned to the evolving scientific understanding of the condition.}, } @article {pmid39142505, year = {2024}, author = {Vogel, JM and Pollack, B and Spier, E and McCorkell, L and Jaudon, TW and Fitzgerald, M and Davis, H and Cohen, AK}, title = {Designing and optimizing clinical trials for long COVID.}, journal = {Life sciences}, volume = {355}, number = {}, pages = {122970}, doi = {10.1016/j.lfs.2024.122970}, pmid = {39142505}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; *Clinical Trials as Topic ; *Research Design ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Drug Repositioning/methods ; }, abstract = {Long COVID is a debilitating, multisystemic illness following a SARS-CoV-2 infection whose duration may be indefinite. Over four years into the pandemic, little knowledge has been generated from clinical trials. We analyzed the information available on ClinicalTrials.gov, and found that the rigor and focus of trials vary widely, and that the majority test non-pharmacological interventions with insufficient evidence. We highlight promising trials underway, and encourage the proliferation of clinical trials for treating Long COVID and other infection-associated chronic conditions and illnesses (IACCIs). We recommend several guidelines for Long COVID trials: First, pharmaceutical trials with potentially curative, primary interventions should be prioritized, and both drug repurposing and new drug development should be pursued. Second, study designs should be both rigorous and accessible, e.g., triple-blinded randomized trials that can be conducted remotely, without participants needing to leave their homes. Third, studies should have multiple illness comparator cohorts for IACCIs such as myalgic encephalomyelitis (ME/CFS) and dysautonomia, and screen for the full spectrum of symptomatology and pathologies of these illnesses. Fourth, studies should consider inclusion/exclusion criteria with an eye towards equity and breadth of representation, including participants of all races, ethnicities, and genders most impacted by COVID-19, and including all levels of illness severity. Fifth, involving patient-researchers in all aspects of studies brings immensely valuable perspectives that will increase the impact of trials. We also encourage the development of efficient clinical trial designs including methods to study several therapies in parallel.}, } @article {pmid39142425, year = {2024}, author = {Neuhouser, ML and Butt, HI and Hu, C and Shadyab, AH and Garcia, L and Follis, S and Mouton, C and Harris, HR and Wactawski-Wende, J and Gower, EW and Vitolins, M and Von Ah, D and Nassir, R and Karanth, S and Ng, T and Paskett, E and Manson, JE and Chen, Z}, title = {Risk factors for long COVID syndrome in postmenopausal women with previously reported diagnosis of COVID-19.}, journal = {Annals of epidemiology}, volume = {98}, number = {}, pages = {36-43}, pmid = {39142425}, issn = {1873-2585}, support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; HHSN268201100046C/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; HHSN261201700010C/CA/NCI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19/epidemiology/diagnosis ; *Postmenopause ; Risk Factors ; *Post-Acute COVID-19 Syndrome ; Aged ; *SARS-CoV-2 ; Aged, 80 and over ; Middle Aged ; United States/epidemiology ; }, abstract = {PURPOSE: Long COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.

METHODS: Data are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.

RESULTS: Of n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).

CONCLUSIONS: Knowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.}, } @article {pmid39142233, year = {2024}, author = {Chesdachai, S and Rivera, CG and Rosedahl, JK and Philpot, LM and Dholakia, R and Borah, BJ and Draper, EW and Arndt, R and Ganesh, R and Larsen, JJ and Destro Borgen, MJ and Razonable, RR}, title = {Outpatient remdesivir treatment program for hospitalized patients with coronavirus disease-2019: Patient perceptions, process and economic impact.}, journal = {Healthcare (Amsterdam, Netherlands)}, volume = {12}, number = {4}, pages = {100750}, doi = {10.1016/j.hjdsi.2024.100750}, pmid = {39142233}, issn = {2213-0772}, mesh = {Humans ; *Adenosine Monophosphate/analogs & derivatives/therapeutic use/economics ; *Alanine/analogs & derivatives/therapeutic use/economics ; Male ; Female ; Middle Aged ; *COVID-19 Drug Treatment ; *Antiviral Agents/therapeutic use/economics ; Aged ; Hospitalization/statistics & numerical data/economics ; COVID-19/economics ; Ambulatory Care/economics/statistics & numerical data ; SARS-CoV-2 ; Adult ; Patient Satisfaction/statistics & numerical data ; Outpatients/statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In a prior work, patients who continued remdesivir in an outpatient setting experienced better 28-day clinical outcomes. Here, we assessed patients' perspectives and the economic impact of this outpatient practice.

METHODS: Hospitalized patients who received remdesivir for COVID-19 at Mayo Clinic, Rochester, from 11/6/2020 to 11/5/2021 and were dismissed to continue remdesivir in the outpatient setting were surveyed. The cost of care was compared between those who remained hospitalized versus those who were dismissed.

RESULTS: 93 (19.8 %) among 470 eligible patients responded to the electronic survey. Responders were older than non-responders. The majority (70.5 %) had symptoms resolved by the time of the survey. Ten (11.4 %) patients had persistent symptoms attributed to long COVID-19. The majority were satisfied with the quality of care (82.3 %) and overall experience (76.0 %) in the infusion clinic. After adjusting for gender, comorbidity score, and WHO severity scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p < .01). An estimate of 1,077 hospital bed-days were made available to other patients as a result of this transition to outpatient.

CONCLUSION: An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital beds for other patients needing critical services.}, } @article {pmid39141921, year = {2024}, author = {Mwangi, J and Siegelman, JN}, title = {Long-Term Effects of COVID-19: The Stories of 2 Physicians Who Became Patients.}, journal = {Topics in antiviral medicine}, volume = {32}, number = {2}, pages = {431-436}, pmid = {39141921}, issn = {2161-5853}, mesh = {Humans ; *COVID-19/complications ; Physicians ; SARS-CoV-2 ; Male ; Female ; Post-Acute COVID-19 Syndrome ; Middle Aged ; }, abstract = {Approximately 10% of patients who survive COVID-19 will proceed to have lasting, often debilitating effects, known as "long COVID." These symptoms can take various forms, most commonly including postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, diminished sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Here, 2 physician-patients present their own experiences with long COVID and share their perspectives on the experience. One key insight is that patients who are not familiar with long COVID may not attribute ongoing symptoms to their illness. Diagnosis requires an astute, compassionate physician who understands long COVID and can appropriately situate the symptoms within the evolving understanding of the condition, leading the patient toward recovery.}, } @article {pmid39138793, year = {2024}, author = {Fekete, M and Liotta, EM and Molnar, T and Fülöp, GA and Lehoczki, A}, title = {The role of atrial fibrillation in vascular cognitive impairment and dementia: epidemiology, pathophysiology, and preventive strategies.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39138793}, issn = {2509-2723}, support = {RRF-2.3.1-21-2022-00003//Nemzeti Kutatási, Fejlesztési és Innovaciós Alap/ ; }, abstract = {The aging population in Europe faces a substantial burden from dementia, with vascular cognitive impairment and dementia (VCID) being a preventable cause. Atrial fibrillation (AF), a common cardiac arrhythmia, increases the risk of VCID through mechanisms such as thromboembolism, cerebral hypoperfusion, and inflammation. This review explores the epidemiology, pathophysiology, and preventive strategies for AF-related VCID. Epidemiological data indicate that AF prevalence rises with age, affecting up to 12% of individuals over 80. Neuroimaging studies reveal chronic brain changes in AF patients, including strokes, lacunar strokes, white matter hyperintensities (WMHs), and cerebral microbleeds (CMHs), while cognitive assessments show impairments in memory, executive function, and attention. The COVID-19 pandemic has exacerbated the underdiagnosis of AF, leading to an increase in undiagnosed strokes and cognitive impairment. Many elderly individuals did not seek medical care due to fear of exposure, resulting in delayed diagnoses. Additionally, reduced family supervision during the pandemic contributed to missed opportunities for early detection of AF and related complications. Emerging evidence suggests that long COVID may also elevate the risk of AF, further complicating the management of this condition. This review underscores the importance of early detection and comprehensive management of AF to mitigate cognitive decline. Preventive measures, including public awareness campaigns, patient education, and the use of smart devices for early detection, are crucial. Anticoagulation therapy, rate and rhythm control, and addressing comorbid conditions are essential therapeutic strategies. Recognizing and addressing the cardiovascular and cognitive impacts of AF, especially in the context of the COVID-19 pandemic, is essential for advancing public health.}, } @article {pmid39138096, year = {2024}, author = {Stewart, C and Ranjan, Y and Conde, P and Sun, S and Zhang, Y and Rashid, Z and Sankesara, H and Cummins, N and Laiou, P and Bai, X and Dobson, RJB and Folarin, AA}, title = {Physiological presentation and risk factors of long COVID in the UK using smartphones and wearable devices: a longitudinal, citizen science, case-control study.}, journal = {The Lancet. Digital health}, volume = {6}, number = {9}, pages = {e640-e650}, doi = {10.1016/S2589-7500(24)00140-7}, pmid = {39138096}, issn = {2589-7500}, mesh = {Humans ; Male ; Female ; Case-Control Studies ; United Kingdom/epidemiology ; *Smartphone ; Risk Factors ; *COVID-19/epidemiology ; Middle Aged ; *Wearable Electronic Devices ; Adult ; Longitudinal Studies ; *Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The emergence of long COVID as a COVID-19 sequela was largely syndromic in characterisation. Digital health technologies such as wearable devices open the possibility to study this condition with passive, objective data in addition to self-reported symptoms. We aimed to quantify the prevalence and severity of symptoms across collected mobile health metrics over 12 weeks following COVID-19 diagnosis and to identify risk factors for the development of post-COVID-19 condition (also known as long COVID).

METHODS: The Covid Collab study was a longitudinal, self-enrolled, community, case-control study. We recruited participants from the UK through a smartphone app, media publications, and promotion within the Fitbit app between Aug 28, 2020, and May 31, 2021. Adults (aged ≥18 years) who reported a COVID-19 diagnosis with a positive antigen or PCR test before Feb 1, 2022, were eligible for inclusion. We compared a cohort of 1200 patients who tested positive for COVID-19 with a cohort of 3600 sex-matched and age-matched controls without a COVID-19 diagnosis. Participants could provide information on COVID-19 symptoms and mental health through self-reported questionnaires (active data) and commercial wearable fitness devices (passive data). Data were compared between cohorts at three periods following diagnosis: acute COVID-19 (0-4 weeks), ongoing COVID-19 (4-12 weeks), and post-COVID-19 (12-16 weeks). We assessed sociodemographic and mobile health risk factors for the development of long COVID (defined as either a persistent change in a physiological signal or self-reported symptoms for ≥12 weeks after COVID-19 diagnosis).

FINDINGS: By Aug 1, 2022, 17 667 participants had enrolled into the study, of whom 1200 (6·8%) cases and 3600 (20·4%) controls were included in the analyses. Compared with baseline (65 beats per min), resting heart rate increased significantly during the acute (0·47 beats per min; odds ratio [OR] 1·06 [95% CI 1·03-1·09]; p<0·0001), ongoing (0·99 beats per min; 1·11 [1·08-1·14]; p<0·0001), and post-COVID-19 (0·52 beats per min; 1·04 [1·02-1·07]; p=0·0017) phases. An increased level of historical activity in the period from 24 months to 6 months preceding COVID-19 diagnosis was protective against long COVID (coefficient -0·017 [95% CI -0·030 to -0·003]; p=0·015). Depressive symptoms were persistently elevated following COVID-19 (OR 1·03 [95% CI 1·01-1·06]; p=0·0033) and were a potential risk factor for developing long COVID (1·14 [1·07-1·22]; p<0·0001).

INTERPRETATION: Mobile health technologies and commercial wearable devices might prove to be a useful resource for tracking recovery from COVID-19 and the prevalence of its long-term sequelae, as well as representing an abundant source of historical data. Mental wellbeing can be impacted negatively for an extended period following COVID-19.

FUNDING: National Institute for Health and Care Research (NIHR), NIHR Maudsley Biomedical Research Centre, UK Research and Innovation, and Medical Research Council.}, } @article {pmid39136010, year = {2024}, author = {Noviello, M and De Lorenzo, R and Chimienti, R and Maugeri, N and De Lalla, C and Siracusano, G and Lorè, NI and Rancoita, PMV and Cugnata, F and Tassi, E and Dispinseri, S and Abbati, D and Beretta, V and Ruggiero, E and Manfredi, F and Merolla, A and Cantarelli, E and Tresoldi, C and Pastori, C and Caccia, R and Sironi, F and Marzinotto, I and Saliu, F and Ghezzi, S and Lampasona, V and Vicenzi, E and Cinque, P and Manfredi, AA and Scarlatti, G and Dellabona, P and Lopalco, L and Di Serio, C and Malnati, M and Ciceri, F and Rovere-Querini, P and Bonini, C}, title = {The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1381091}, pmid = {39136010}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/mortality ; Male ; Female ; Middle Aged ; *Severity of Illness Index ; *SARS-CoV-2/immunology ; Prognosis ; Aged ; Longitudinal Studies ; Adult ; Biomarkers/blood ; CD8-Positive T-Lymphocytes/immunology ; Adaptive Immunity ; Killer Cells, Natural/immunology ; Immunity, Innate ; }, abstract = {INTRODUCTION: SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

METHODS: We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms.

RESULTS: More than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14[+]CD91[+] monocytes, and high CD8[+] Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability.

DISCUSSION: These results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms.}, } @article {pmid39135572, year = {2024}, author = {Brock, MV and Bosmans, F}, title = {A MULTI-HIT MODEL OF LONG COVID PATHOPHYSIOLOGY: THE INTERACTION BETWEEN IMMUNE TRIGGERS AND NERVOUS SYSTEM SIGNALING.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {134}, number = {}, pages = {149-164}, pmid = {39135572}, issn = {0065-7778}, support = {R01 NS126398/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/physiopathology/virology/genetics ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2/immunology ; Signal Transduction ; Genetic Predisposition to Disease ; Primary Dysautonomias/physiopathology/immunology ; Inflammation/immunology/physiopathology ; }, abstract = {Early in the pandemic, clinicians recognized an overlap between Long COVID symptoms and dysautonomia, suggesting autonomic nervous system (ANS) dysfunction. Our clinical experience at Johns Hopkins with primary dysautonomia suggested heritability of sympathetic dysfunction, manifesting primarily as hyperhidrosis and as other dysautonomia symptoms. Whole exome sequencing revealed mutations in genes regulating electrical signaling in the nervous system, thus providing a genetic basis for the sympathetic overdrive observed. We hypothesize that dysautonomia in Long COVID requires two molecular hits: a genetic vulnerability to prime the ANS and a SARS-CoV-2 infection, as an immune trigger, to further disrupt ANS function resulting in increased sympathetic activity. Indeed, Long COVID patients show signs of chronic inflammation and autoimmunity. We have translated this two-hit concept to the clinic using ion channel inhibitors to target genetic susceptibility and immunomodulators to treat inflammation. This multi-hit hypothesis shows promise for managing Long COVID and merits further study.}, } @article {pmid39135185, year = {2024}, author = {Lin, K and Cai, J and Guo, J and Zhang, H and Sun, G and Wang, X and Zhu, K and Xue, Q and Zhu, F and Wang, P and Yuan, G and Sun, Y and Wang, S and Ai, J and Zhang, W}, title = {Multi-omics landscapes reveal heterogeneity in long COVID patients characterized with enhanced neutrophil activity.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {753}, pmid = {39135185}, issn = {1479-5876}, support = {82341033//National Natural Science Foundation of China/ ; 82041010//National Natural Science Foundation of China/ ; SSIII-202305//Autonomous deployment project of Shanghai Sci-Tech InnoCenter for Infection and Immunity/ ; 2022YFC2009801//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *COVID-19/immunology/virology/blood ; *Neutrophils/immunology ; *SARS-CoV-2 ; Male ; Female ; Middle Aged ; *Proteomics ; Transcriptome/genetics ; Antibodies, Neutralizing/blood/immunology ; Adult ; Post-Acute COVID-19 Syndrome ; Viral Load ; Aged ; Gene Expression Profiling ; Neutrophil Activation ; Multiomics ; }, abstract = {BACKGROUND: Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations.

METHODS: We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning.

RESULTS: No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19.

CONCLUSION: The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.}, } @article {pmid39135051, year = {2024}, author = {Mouat, IC and Zhu, L and Aslan, A and McColl, BW and Allan, SM and Smith, CJ and Buckwalter, MS and McCulloch, L}, title = {Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue.}, journal = {Journal of inflammation (London, England)}, volume = {21}, number = {1}, pages = {30}, pmid = {39135051}, issn = {1476-9255}, support = {/WT_/Wellcome Trust/United Kingdom ; 19PABHI34580007//American Heart Institute / Allen Frontiers Group Brain Health Award/ ; 220755/Z/20/Z//Wellcome Sir Henry Dale Fellowship/ ; 19CVD01//Leducq Stroke-IMPaCT Transatlantic Network of Excellence/ ; }, abstract = {BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.

AIMS: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.

METHODS: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher's exact test for categorical data.

RESULTS: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 10[5] ± 4.44 × 10[4] high fatigue versus 4.60 × 10[5] ± 9.28 × 10[4] low fatigue; P = 0.288).

CONCLUSIONS: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.}, } @article {pmid39133926, year = {2024}, author = {Antar, AAR and Auwaerter, PG}, title = {Long COVID Diagnostics: An Unconquered Challenge.}, journal = {Annals of internal medicine}, volume = {177}, number = {9}, pages = {1279-1280}, doi = {10.7326/M24-0892}, pmid = {39133926}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/diagnosis ; *SARS-CoV-2 ; COVID-19 Testing ; Pandemics ; }, } @article {pmid39133715, year = {2024}, author = {Boutry, C and Patel, P and Holmes, J and Radford, K and Bolton, CE and Evangelou, N and das Nair, R and Morriss, R}, title = {Returning to work with long covid in the UK during lockdown and other COVID-19 restrictions: A qualitative study.}, journal = {PloS one}, volume = {19}, number = {8}, pages = {e0307062}, pmid = {39133715}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Return to Work/psychology ; Female ; Male ; United Kingdom/epidemiology ; Middle Aged ; Adult ; *SARS-CoV-2 ; *Qualitative Research ; Fatigue ; }, abstract = {Few previous studies have considered the experiences of people with long covid returning to work beyond symptoms in terms of employer and other support factors. The aim of this research was to understand the experience of returning to work for those with long covid symptoms in contrast to the non-long covid group who had not experienced COVID-19 during the time restrictions were imposed to limit the spread of COVID-19 infection. Twenty-one participants with long covid and 13 participants who had not had COVID-19 were interviewed. Themes were identified from transcripts using framework analysis. Participants with long covid experienced difficulties returning to work, particularly from fatigue, cognitive symptoms and breathlessness. Symptoms were heterogeneous and fluctuated in severity over time. A lack of understanding from colleagues and managers sometimes led to a premature return to work without adequate support, associated with further long covid relapse. Outside-of-work, support was salient for a successful return to work. The standard phased return offered by employers may be too short and rigid for some people with long covid. They may benefit from a tailored intervention to support a return to work that targets symptom management, and engages with work colleagues, managers, and family members.}, } @article {pmid39133434, year = {2024}, author = {Saxena, A and Mautner, J}, title = {A Disease Hidden in Plain Sight: Pathways and Mechanisms of Neurological Complications of Post-acute Sequelae of COVID-19 (NC-PASC).}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39133434}, issn = {1559-1182}, abstract = {The global impact of coronavirus disease 2019 (COVID-19) marked by numerous pandemic peaks is attributed to its high variability and infectious nature, transforming it into a persistent global public health concern. With hundreds of millions of cases reported globally, the illness is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its initial classification as an acute respiratory illness, recent evidence indicates that lingering effects on various bodily systems, such as cardiovascular, pulmonary, nervous, gastrointestinal (GI), and musculoskeletal, may endure well beyond the acute phase. These persistent manifestations following COVID-19, commonly known as long COVID, have the potential to affect individuals across the entire range of illness severity, with a tendency to be more prevalent in mild to moderate cases. At present, there are no established criteria for diagnosing long COVID. Nonetheless, it is conceptualized as a multi-organ disorder encompassing a diverse array of clinical manifestations. The most common, persistent, and debilitating symptoms of long COVID may be neurological, known as neurological complications of post-acute sequelae of COVID-19 (NC-PASC). More than one-third of individuals with a prior SARS-CoV-2 infection show involvement of both the central nervous system (CNS) and peripheral nervous system (PNS), as evidenced by an approximately threefold higher incidence of neurological symptoms in observational studies. The persistent neurological symptoms of long COVID encompass fatigue, headache, cognitive decline, "brain fog", dysautonomia, neuropsychiatric issues, loss of smell (anosmia), loss of taste (ageusia), and peripheral nerve problems (peripheral neuropathy). Reported pathogenic mechanisms encompass viral persistence and neuro-invasion by SARS-CoV-2, neuroinflammation, autoimmunity, coagulopathy, and endotheliopathy. Raising awareness of potential complications is crucial for preventing and alleviating the long-term effects of long COVID and enhancing the prognosis for affected patients. This review explores the hypothetical pathophysiological mechanisms and pathways of NC-PASC with a sole aim to increase awareness about this crippling disease.}, } @article {pmid39132241, year = {2024}, author = {Khakshooy, A and Chiappelli, F}, title = {Post-acute CoVid-19 syndrome (PACS) linked cardiovascular symptoms.}, journal = {Bioinformation}, volume = {20}, number = {5}, pages = {412-414}, pmid = {39132241}, issn = {0973-2063}, abstract = {Officials have marked the end of the CoVid-19 pandemic, yet we continue to learn more about the SARS-CoV2 virus itself and its lasting multidimensional effects after acute infection. Long COVID, or the post-acute CoViD-19 syndrome (PACS), manifests as a wide range of prolonged physical, mental, and emotional symptoms over at least 1 to 12 months after SARS-CoV2 infection. Here, we describe certain pervasive clinical consequences of PACS on the cardiovascular system, and insight on the potentially improved prognoses in heart failure patients.}, } @article {pmid39130813, year = {2024}, author = {Rodriguez-Nava, G and El Kamari, V and Chang, H and Egoryan, G and Bonilla, HF}, title = {New-onset sarcoidosis in a patient with long COVID.}, journal = {Clinical case reports}, volume = {12}, number = {8}, pages = {e9186}, pmid = {39130813}, issn = {2050-0904}, abstract = {Long COVID, often following SARS-CoV-2 infection, may stem from sustained inflammation, overlapping with autoimmune diseases like sarcoidosis. Though specific treatments lack, this link could shape future diagnostic and therapeutic methods.}, } @article {pmid39129752, year = {2024}, author = {Ritter, O and Noureddine, S and Laurent, L and Roux, P and Westeel, V and Barnig, C}, title = {Unraveling persistent dyspnea after mild COVID: insights from a case series on hyperventilation provocation tests.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1394642}, pmid = {39129752}, issn = {1664-042X}, abstract = {Dyspnea is a common yet poorly understood symptom of long COVID, affecting many patients. This brief report examines the role of dysfunctional breathing in persistent dyspnea among patients with mild post-COVID-19 using hyperventilation provocation tests (HVPT). In this case series, six patients with unexplained dyspnea and normal cardiopulmonary function underwent HVPT. Despite normal exercise testing results, all patients exhibited delayed PETCO2 recovery, indicative of a hyperventilation pattern consistent with chronic hyperventilation syndrome, without typical symptomatic manifestations. These findings suggest underlying post-COVID respiratory dysregulation, emphasizing the importance of targeted diagnostic and therapeutic approaches for persistent respiratory symptoms in long COVID patients.}, } @article {pmid39129538, year = {2024}, author = {Xu, Z and Wang, W and Zhang, D and Tam, KW and Li, Y and Chan, DCC and Yang, Z and Wong, SYS}, title = {Excess risks of long COVID symptoms compared with identical symptoms in the general population: A systematic review and meta-analysis of studies with control groups.}, journal = {Journal of global health}, volume = {14}, number = {}, pages = {05022}, pmid = {39129538}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is important to understand the excess risks of symptoms of long COVID when compared to the same symptoms in the general population. We aimed to evaluate the association between coronavirus disease 2019 (COVID-19) infection and various long-term symptoms.

METHODS: We conducted a systematic review and meta-analysis of studies measuring long COVID symptoms lasting for at least three months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in comparison to non-COVID-19 control groups. We searched MEDLINE and Embase (via Ovid), CINAHL (via EBSCOhost), the ProQuest Coronavirus Research Database, and the World Health Organization COVID-19 Research Database for relevant literature on 14 February 2023. The symptom list had 10 categories with 29 symptoms, including general, neurologic, respiratory, cardiac, dermatologic, eye, ear, musculoskeletal, psychiatric, and gastrointestinal symptoms. We performed random-effects meta-analysis and summarised the results using odds ratios (OR) and 95% confidence intervals (CI), after which we conducted subgroup analyses.

RESULTS: We included 51 studies with 17 901 204 participants (range of mean age: 5.9-65.4 years; range of proportion of women: 11.2-96.0%). In the primary analysis, participants with COVID-19 had a significantly higher risk of having at least one long COVID symptom (OR = 2.032; 95% CI = 1.787-2.310). Specifically, they had higher risks of 25 symptoms, the highest of which were for smell (OR = 8.474; 95% CI = 6.357-11.295), taste (OR = 5.881; 95% CI = 3.818-9.059), post-exertional malaise (OR = 3.187; 95% CI = 2.602-3.904), shortness of breath (OR = 2.497; 95% CI = 2.125-2.935), brain fog (OR = 2.093; 95% CI = 1.362-3.218), hair loss (OR = 2.082; 95% CI = 1.291-3.358), chest pain (OR = 2.056; 95% CI = 1.692-2.498), cognitive decline (OR = 1.992; 95% CI = 1.560-2.544), palpitations (OR = 1.986; 95% CI = 1.647-2.395), and fatigue (OR = 1.971; 95% CI = 1.781-2.182). We found significant differences between studies with different follow-up times in cognitive decline, dizziness, palpitations, and sleep problems (P < 0.05). Adults had significantly higher risks of cognitive decline, hair loss, and joint pain than children (P < 0.05).

CONCLUSIONS: We found that COVID-19 can significantly increase the risk of many long COVID symptoms, without differences due to gender, age, or decrease over time after three months post-infection. This highlights that services and interventions for long COVID symptoms are needed.

REGISTRATION: PROSPERO (CRD42023409847).}, } @article {pmid39128056, year = {2024}, author = {Tunçay, E and Moçin, Ö and Ediboğdu, Ö and Adıgüzel, N and Güngör, S and İşcanlı, İ and Er, B and Mendil, NA and Usalan, A and Yılmaz, D and Keskin, H and Dönmez, GE and Yılmaz, B and Kargın, F and Saraçoğlu, KT and Temel, Ş and Dal, HC and Turan, S and Talan, L and Hoşgün, D and Aydemir, S and Sungurtekin, H}, title = {Evaluation of Long-Coronavirus Disease 2019 Cases Readmitted to Intensive Care Units Due to Acute Respiratory Failure: Point Prevalence Study.}, journal = {Thoracic research and practice}, volume = {25}, number = {4}, pages = {162-167}, pmid = {39128056}, issn = {2979-9139}, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused morbidity and mortality worldwide. Besides the acute effects, subacute and long-term effects are defined as long-COVID causing morbidity. The intensive care unit (ICU) data of long-COVID-19 cases were evaluated with the participation of 11 centers.

MATERIAL AND METHODS:  Study was designed by Turkish Thoracic Society Respiratory Failure and Intensive Care Working Group to evaluate long COVID-19 patients. All patients followed up in the ICU with long-COVID diagnosis were included in point prevelance study.

RESULTS:  A total of 41 long COVID-19 patients from 11 centers were included in the study. Half of the patients were male, mean age was 66 ± 14, body mass index was 27 ± 5. Hypertension, diabetes mellitus, lung cancer, malignancy, and heart failure rates were 27%, 51%, 34%, 34%, and 27%, respectively. Eighty percent had received COVID vaccine. Patients had moderate hypoxemic respiratory failure. APACHE II, SOFA score was 18 (14-26), 6 (3-8), respectively. Forty-six percent received invasive mechanical ventilator support, 42% were sepsis, 17% were septic shock. Bilateral (67%), interstitial involvement (37%) were most common in chest x-ray. Fibrosis (27%) was detected in thorax tomography. Seventy-one percent of patients received antibiotherapy (42% carbapenem, 22% linezolid). Sixty-one percent of the patients received corticosteroid treatment.

CONCLUSION:  More than half of the patients had pneumonia and the majority of them used broad-spectrum antibiotics. Presence of comorbidities and malignancies, intensive care severity scores, intubation, and sepsis rates were high. Receiving corticosteroid treatment and extensive bilateral radiologic involvement due to COVID-19 might be the reasons for the high re-admission rate for the ICUs.}, } @article {pmid39127990, year = {2024}, author = {Hoffmann, K and Stingl, M and O'Mahony, L and Untersmayr, E}, title = {A Practical Approach to Tailor the Term Long COVID for Diagnostics, Therapy and Epidemiological Research for Improved Long COVID Patient Care.}, journal = {Infectious diseases and therapy}, volume = {13}, number = {9}, pages = {1921-1928}, pmid = {39127990}, issn = {2193-8229}, abstract = {The term long COVID (LC) effectively describes the broad long-term disease burden of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections, encompassing individual suffering and significant socioeconomic impacts. However, its general use hampers precise epidemiological research, diagnostics and therapeutic strategies. Misinterpretations occur, for example, when population surveys are compared to studies using health record data, because both refer to these data as LC. This also emphasizes the need for different terminology. The National Institute for Health and Care Excellence (NICE) rapid guideline differentiates ongoing symptomatic COVID-19 from post-COVID conditions, yet real-world observations challenge these two subgroup definitions. We propose refining the term LC into three subgroups: ongoing symptomatic COVID-19, SARS-CoV-2 induced or exacerbated diseases and post-acute COVID condition. This stratification aids targeted diagnostics, treatment and epidemiological research. Subgroup-specific documentation using the International Classification of Diseases, Tenth Revision (ICD-10) codes ensures accurate tracking and understanding of long-term effects. The subgroup of post-acute COVID condition again includes various symptoms, syndromes and diseases like post-exertional malaise (PEM), dysautonomia or cognitive dysfunctions. In this regard, differentiation, especially considering PEM, is crucial for effective diagnostics and treatment.}, } @article {pmid39127446, year = {2024}, author = {Shrestha, A and Chen, R and Kunasekaran, M and Honeyman, D and Notaras, A and Sutton, B and Quigley, A and MacIntyre, CR}, title = {The risk of cognitive decline and dementia in older adults diagnosed with COVID-19: A systematic review and meta-analysis.}, journal = {Ageing research reviews}, volume = {101}, number = {}, pages = {102448}, doi = {10.1016/j.arr.2024.102448}, pmid = {39127446}, issn = {1872-9649}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Cognitive Dysfunction/epidemiology/psychology/diagnosis/etiology ; *COVID-19/psychology/complications/epidemiology ; *Dementia/diagnosis/epidemiology/etiology/psychology ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Cognitive impairment can be caused by infections with various pathogens, including SARS-CoV-2. Research has yet to determine the true incidence and course of cognitive impairment in older adults following COVID-19. Furthermore, research has theorised that COVID-19 is associated with dementia progression and diagnosis but this association has yet to be fully described.

METHODS: A systematic review was registered in Prospero and conducted on the databases PubMed, Embase, Ovid, CENTRAL and Cochrane Library. Studies reporting cognitive impairment and dementia outcomes in post-acute and post-COVID-19 patients aged ≥65 years, and which included control data, were included in this review.

RESULTS: 15,124 articles were identified by the search strategy. After eliminating duplicate titles and completing title, abstracts and full-text review, 18 studies were included comprising of 412,957 patients with COVID-19 (46.63 % male) and 411,929 patients without COVID-19 (46.59 % male). The overall mean Montreal Cognitive Assessment (MoCA) score in COVID-19 patients was 23.34 out of 30 (95 % CI [22.24, 24.43]). indicating cognitive impairment. The overall proportion of patients identified as having new onset cognitive impairment was 65 % (95 % CI [44,81]). Subgroup analyses indicated that time since infection significantly improves overall MoCA score and reduces proportion of patients with cognitive impairment.

CONCLUSION: This study indicates that cognitive impairment may be an important sequela of COVID-19. Further research with adequate sample sizes is warranted regarding COVID-19's association with new-onset dementia and dementia progression, and the effect of repeat infections. There is a need for development of diagnostic and management protocols for COVID-19 patients with cognitive impairment.}, } @article {pmid39127387, year = {2024}, author = {Goldberg, J and Rabinovitch, N and Bender, B}, title = {Long COVID in pediatric patients with chronic health issues: How to assess and support.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {133}, number = {5}, pages = {491-492}, doi = {10.1016/j.anai.2024.08.003}, pmid = {39127387}, issn = {1534-4436}, } @article {pmid39127120, year = {2024}, author = {Brihmat, N and Bayram, MB and Bheemreddy, A and Saleh, S and Yue, GH and Forrest, GF}, title = {Insights into COVID-19 pathophysiology from a longitudinal multisystem report during acute infection.}, journal = {Experimental neurology}, volume = {380}, number = {}, pages = {114917}, doi = {10.1016/j.expneurol.2024.114917}, pmid = {39127120}, issn = {1090-2430}, mesh = {Humans ; *COVID-19/complications/physiopathology ; Longitudinal Studies ; *Post-Acute COVID-19 Syndrome ; Male ; SARS-CoV-2 ; Female ; Acute Disease ; Middle Aged ; Adult ; Magnetic Resonance Imaging ; }, abstract = {The Coronavirus disease 2019 (COVID-19), an illness caused by a SARS-CoV-2 viral infection, has been associated with neurological and neuropsychiatric disorders, revealing its impact beyond the respiratory system. Most related research involved individuals with post-acute or persistent symptoms of COVID-19, also referred to as long COVID or Post-Acute Sequelae of COVID-19 (PASC). In this longitudinal unique report, we aimed to describe the acute supraspinal and corticospinal changes and functional alterations induced by a COVID-19 infection using neuroimaging, neurophysiological and clinical assessment of a participant during acute infection, as compared to three other visits where the participant had no COVID-19. The results favor a multisystem impairment, impacting cortical activity, functional connectivity, and corticospinal excitability, as well as motor and cardiovascular function. The report suggests pathophysiological alteration and impairment already present at the acute stage, that if resolved tend to lead to a full clinical recovery. Such results could be also insightful into PASC symptomatology.}, } @article {pmid39127088, year = {2024}, author = {Almulla, AF and Thipakorn, Y and Zhou, B and Vojdani, A and Maes, M}, title = {Immune activation and immune-associated neurotoxicity in Long-COVID: A systematic review and meta-analysis of 103 studies comprising 58 cytokines/chemokines/growth factors.}, journal = {Brain, behavior, and immunity}, volume = {122}, number = {}, pages = {75-94}, doi = {10.1016/j.bbi.2024.07.036}, pmid = {39127088}, issn = {1090-2139}, mesh = {Humans ; C-Reactive Protein/metabolism ; *Chemokines/immunology ; *COVID-19/immunology ; *Cytokines/immunology ; *Intercellular Signaling Peptides and Proteins/metabolism ; Neurotoxicity Syndromes/immunology ; *Post-Acute COVID-19 Syndrome/immunology ; }, abstract = {BACKGROUND: Multiple studies have shown that Long COVID (LC) disease is associated with heightened immune activation, as evidenced by elevated levels of inflammatory mediators. However, there is no comprehensive meta-analysis focusing on activation of the immune inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS) along with other immune phenotypes in LC patients.

OBJECTIVES: This meta-analysis is designed to explore the IRS and CIRS profiles in LC patients, the individual cytokines, chemokines, growth factors, along with C-reactive protein (CRP) and immune-associated neurotoxicity.

METHODS: To gather relevant studies for our research, we conducted a thorough search using databases such as PubMed, Google Scholar, and SciFinder, covering all available literature up to July 5th, 2024.

RESULTS: The current meta-analysis encompassed 103 studies that examined multiple immune profiles, C-reactive protein, and 58 cytokines/chemokines/growth factors in 5502 LC patients versus 5962 normal controls (NC). LC patients showed significant increases in IRS/CIRS ratio (standardized mean difference (SMD: 0.156, confidence interval (CI): 0.062;0.250), IRS (SMD: 0.338, CI: 0.236;0.440), M1 macrophage (SMD: 0.371, CI: 0.263;0.480), T helper (Th)1 (SMD: 0.316, CI: 0.185;0.446), Th17 (SMD: 0.439, CI: 0.302;0.577) and immune-associated neurotoxicity (SMD: 0.384, CI: 0.271;0.497). In addition, CRP and 21 different cytokines displayed significantly elevated levels in LC patients compared to NC.

CONCLUSION: LC disease is characterized by IRS activation and increased immune-associated neurotoxicity.}, } @article {pmid39127085, year = {2024}, author = {Zha, S and Liu, X and Yao, Y and He, Y and Wang, Y and Zhang, Q and Zhang, J and Yi, Y and Xiao, R and Hu, K}, title = {Short-term intermittent hypoxia exposure for dyspnea and fatigue in post-acute sequelae of COVID-19: A randomized controlled study.}, journal = {Respiratory medicine}, volume = {232}, number = {}, pages = {107763}, doi = {10.1016/j.rmed.2024.107763}, pmid = {39127085}, issn = {1532-3064}, mesh = {Humans ; *Dyspnea/physiopathology/etiology ; Male ; Female ; *COVID-19/complications/physiopathology ; *Fatigue/etiology/physiopathology ; Middle Aged ; Prospective Studies ; *Post-Acute COVID-19 Syndrome ; *Hypoxia/physiopathology ; Adult ; Walk Test/methods ; Aged ; Spirometry/methods ; China ; }, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC.

METHODS: This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565).

FINDINGS: Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported.

INTERPRETATION: IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.}, } @article {pmid39125881, year = {2024}, author = {Lizcano-Álvarez, Á and Varillas-Delgado, D and Cano-de-la-Cuerda, R and Jiménez-Antona, C and Melián-Ortiz, A and Molero-Sánchez, A and Laguarta-Val, S}, title = {The Association of Genetic Markers Involved in Muscle Performance Responding to Lactate Levels during Physical Exercise Therapy by Nordic Walking in Patients with Long COVID Syndrome: A Nonrandomized Controlled Pilot Study.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125881}, issn = {1422-0067}, mesh = {Humans ; Male ; *Exercise Therapy/methods ; Female ; *COVID-19/genetics/therapy ; Pilot Projects ; Middle Aged ; *Walking ; *Actinin/genetics ; *Lactic Acid/blood ; Aged ; SARS-CoV-2 ; Genetic Markers ; AMP Deaminase/genetics ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Single Nucleotide ; Post-Acute COVID-19 Syndrome ; Muscle, Skeletal/metabolism ; Genotype ; }, abstract = {Several genetic markers have shown associations with muscle performance and physical abilities, but the response to exercise therapy is still unknown. The aim of this study was to test the response of patients with long COVID through an aerobic physical therapy strategy by the Nordic walking program and how several genetic polymorphisms involved in muscle performance influence physical capabilities. Using a nonrandomized controlled pilot study, 29 patients who previously suffered from COVID-19 (long COVID = 13, COVID-19 = 16) performed a Nordic walking exercise therapy program for 12 sessions. The influence of the ACE (rs4646994), ACTN3 (rs1815739), AMPD1 (rs17602729), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms, genotyped by using single nucleotide primer extension (SNPE) in lactic acid concentration was established with a three-way ANOVA (group × genotype × sessions). For ACE polymorphism, the main effect was lactic acid (p = 0.019). In ACTN3 polymorphism, there were no main effects of lactic acid, group, or genotype. However, the posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CT and TT genotypes (all p < 0.05). For AMPD1 polymorphism, there were main effects of lactic acid, group, or genotype and lactic acid × genotype or lactic acid × group × genotype interactions (all p < 0.05). The posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CC and CT genotypes (all p < 0.05). Physical therapy strategy through Nordic walking enhanced physical capabilities during aerobic exercise in post-COVID19 patients with different genotypes in ACTN3 c.1729C>T and AMPD1 c.34C>T polymorphisms. These findings suggest that individuals who reported long COVID who presumably exercised less beforehand appeared to be less able to exercise, based on lactate levels, and the effect of aerobic physical exercise enhanced physical capabilities conditioned by several genetic markers in long COVID patients.}, } @article {pmid39125722, year = {2024}, author = {Chung, YS and Lam, CY and Tan, PH and Tsang, HF and Wong, SC}, title = {Comprehensive Review of COVID-19: Epidemiology, Pathogenesis, Advancement in Diagnostic and Detection Techniques, and Post-Pandemic Treatment Strategies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125722}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/virology ; *SARS-CoV-2/isolation & purification ; Pandemics ; COVID-19 Testing/methods ; }, abstract = {At present, COVID-19 remains a public health concern due to the ongoing evolution of SARS-CoV-2 and its prevalence in particular countries. This paper provides an updated overview of the epidemiology and pathogenesis of COVID-19, with a focus on the emergence of SARS-CoV-2 variants and the phenomenon known as 'long COVID'. Meanwhile, diagnostic and detection advances will be mentioned. Though many inventions have been made to combat the COVID-19 pandemic, some outstanding ones include multiplex RT-PCR, which can be used for accurate diagnosis of SARS-CoV-2 infection. ELISA-based antigen tests also appear to be potential diagnostic tools to be available in the future. This paper also discusses current treatments, vaccination strategies, as well as emerging cell-based therapies for SARS-CoV-2 infection. The ongoing evolution of SARS-CoV-2 underscores the necessity for us to continuously update scientific understanding and treatments for it.}, } @article {pmid39123312, year = {2024}, author = {Morrow, AK and Villatoro, C and Kokorelis, C and Rowe, PC and Malone, LA}, title = {Orthostatic Intolerance in Children With Long COVID Utilizing a 10-Minute Passive Standing Test.}, journal = {Clinical pediatrics}, volume = {}, number = {}, pages = {99228241272053}, doi = {10.1177/00099228241272053}, pmid = {39123312}, issn = {1938-2707}, support = {U18 HS029920/HS/AHRQ HHS/United States ; }, abstract = {Despite there being a wide variety of symptoms reported in pediatric long COVID, one condition that has become increasingly recognized is orthostatic intolerance (OI), which can cause significant morbidity, limiting activities of daily living. This study examines rates of OI in 92 children with long COVID who underwent a bedside passive standing test in a pediatric post-COVID-19 rehabilitation clinic. Seventy-one percent met criteria for an orthostatic condition, including postural orthostatic tachycardia syndrome (POTS), orthostatic tachycardia (OT), classic orthostatic hypotension (OH), delayed OH, and orthostatic hypertension. Our findings suggest that OI is common in pediatric long COVID, necessitating appropriate clinical screening and treatment.}, } @article {pmid39122965, year = {2024}, author = {Al-Aly, Z and Davis, H and McCorkell, L and Soares, L and Wulf-Hanson, S and Iwasaki, A and Topol, EJ}, title = {Long COVID science, research and policy.}, journal = {Nature medicine}, volume = {30}, number = {8}, pages = {2148-2164}, pmid = {39122965}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Health Policy ; Global Health ; Biomedical Research/trends ; }, abstract = {Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system and can be severely disabling. The cumulative global incidence of long COVID is around 400 million individuals, which is estimated to have an annual economic impact of approximately $1 trillion-equivalent to about 1% of the global economy. Several mechanistic pathways are implicated in long COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, endothelial inflammation and microbiome dysbiosis. Long COVID can have devastating impacts on individual lives and, due to its complexity and prevalence, it also has major ramifications for health systems and economies, even threatening progress toward achieving the Sustainable Development Goals. Addressing the challenge of long COVID requires an ambitious and coordinated-but so far absent-global research and policy response strategy. In this interdisciplinary review, we provide a synthesis of the state of scientific evidence on long COVID, assess the impacts of long COVID on human health, health systems, the economy and global health metrics, and provide a forward-looking research and policy roadmap.}, } @article {pmid39121972, year = {2024}, author = {Wang, HI and Doran, T and Crooks, MG and Khunti, K and Heightman, M and Gonzalez-Izquierdo, A and Qummer Ul Arfeen, M and Loveless, A and Banerjee, A and Van Der Feltz-Cornelis, C}, title = {Prevalence, risk factors and characterisation of individuals with long COVID using Electronic Health Records in over 1.5 million COVID cases in England.}, journal = {The Journal of infection}, volume = {89}, number = {4}, pages = {106235}, pmid = {39121972}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; *Electronic Health Records ; England/epidemiology ; Risk Factors ; Middle Aged ; Prevalence ; Adult ; Aged ; Longitudinal Studies ; *SARS-CoV-2 ; Young Adult ; Adolescent ; Post-Acute COVID-19 Syndrome ; Hospitalization/statistics & numerical data ; Aged, 80 and over ; Child ; }, abstract = {OBJECTIVES: This study examines clinically confirmed long-COVID symptoms and diagnosis among individuals with COVID in England, aiming to understand prevalence and associated risk factors using electronic health records. To further understand long COVID, the study also explored differences in risks and symptom profiles in three subgroups: hospitalised, non-hospitalised, and untreated COVID cases.

METHODS: A population-based longitudinal cohort study was conducted using data from 1,554,040 individuals with confirmed SARS-CoV-2 infection via Clinical Practice Research Datalink. Descriptive statistics explored the prevalence of long COVID symptoms 12 weeks post-infection, and Cox regression models analysed the associated risk factors. Sensitivity analysis was conducted to test the impact of right-censoring data.

RESULTS: During an average 400-day follow-up, 7.4% of individuals with COVID had at least one long-COVID symptom after acute phase, yet only 0.5% had long-COVID diagnostic codes. The most common long-COVID symptoms included cough (17.7%), back pain (15.2%), stomach-ache (11.2%), headache (11.1%), and sore throat (10.0%). The same trend was observed in all three subgroups. Risk factors associated with long-COVID symptoms were female sex, non-white ethnicity, obesity, and pre-existing medical conditions like anxiety, depression, type II diabetes, and somatic symptom disorders.

CONCLUSIONS: This study is the first to investigate the prevalence and risk factors of clinically confirmed long-COVID in the general population. The findings could help clinicians identify higher risk individuals for timely intervention and allow decision-makers to more efficiently allocate resources for managing long-COVID.}, } @article {pmid39120254, year = {2024}, author = {Rodríguez-Pérez, MP and Pérez-de-Heredia-Torres, M and Rodríguez-Ledo, P and Fernández-Gómez, G and García-Bravo, C and Cano-de-la-Cuerda, R and Sánchez-Herrera-Baeza, P}, title = {Post-COVID-19 Condition: How Sociodemographic Factors, Physical Well-Being and Functionality Influence Quality of Life and Mental Health Symptoms.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {15}, pages = {}, pmid = {39120254}, issn = {2227-9032}, abstract = {BACKGROUND: Long COVID-19 syndrome remains a global public health problem, with more than 145 million people affected with multisystemic symptoms. Addressing the requirements of individuals impacted by a syndrome characterised by a complex and variable clinical presentation is of utmost importance. Identifying the variables that can exert influence and understanding their progression is essential for directing treatment strategies aimed at enhancing both independence and quality of life. Therefore, the aim of this study was to analyse the influence of sociodemographic and clinical variables on existence and their relationship with asthenia, anxiety symptoms and low mood.

METHODS: An analytical study secondary to an observational cross-sectional descriptive study.

RESULTS: Logistic regression showed significant univariate effects on asthenia [sex (p = 0.034); age (p = 0.042); Activities of Daily Living Questionnaire [ADQL (p = 0.002)] [physical functioning (p < 0.001) and general health (p = 0.014)] and multivariate [sex (p = 0.019), adult age (p = 0.01) and physical functioning (p = 0.04)]]; low mood [time of evolution (p = 0.028) and multivariate [time course (p = 0.007), ADLQ (p = 0.011), role physical (p = 0.013) and general health (p = 0.001)]] and anxiety [physical functioning (p = 0.046) and multivariate [physical functioning (p = 0.034), age (p = 0.011), time of evolution (p = 0.001) and ADQL (p = 0.011)]].

CONCLUSIONS: Increased age, gender and longer evolution time seem to favour the prevalence and occurrence of mental health symptoms; greater independence and good physical functioning are protective factors with respect to the occurrence of mental health-related symptoms in patients affected by post-COVID-19 condition.}, } @article {pmid39120242, year = {2024}, author = {Jia, G and Su, CH}, title = {Tailored Physical Activity Interventions for Long COVID: Current Approaches and Benefits-A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {15}, pages = {}, pmid = {39120242}, issn = {2227-9032}, support = {Grant No. HXXM-18-10-006//Beijing Jingti da Culture Development Co. , Ltd./ ; }, abstract = {This narrative review explores the essential role of physical activity in managing long COVID, which is characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. In this context, "physical activity" includes various exercises, such as aerobic and resistance training, as well as flexibility and balance exercises, thereby encompassing the subset known as "exercise". The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 to June 2024 focusing on long COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like the Consensus on Exercise Reporting Template (CERT), and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity or exercise programs in standard care for long COVID to improve patient outcomes and quality of life.}, } @article {pmid39117999, year = {2024}, author = {Mustonen, T and Kanerva, M and Luukkonen, R and Lantto, H and Uusitalo, A and Piirilä, P}, title = {Cardiopulmonary exercise testing in long covid shows the presence of dysautonomia or chronotropic incompetence independent of subjective exercise intolerance and fatigue.}, journal = {BMC cardiovascular disorders}, volume = {24}, number = {1}, pages = {413}, pmid = {39117999}, issn = {1471-2261}, mesh = {Humans ; *COVID-19/complications/diagnosis/physiopathology ; Male ; Female ; *Exercise Tolerance ; Middle Aged ; *Exercise Test ; *Primary Dysautonomias/physiopathology/diagnosis ; *Fatigue/physiopathology/diagnosis/etiology ; *Heart Rate ; Aged ; Post-Acute COVID-19 Syndrome ; Adult ; Oxygen Consumption ; Time Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: After COVID-19 infection, 10-20% of patients suffer from varying symptoms lasting more than 12 weeks (Long COVID, LC). Exercise intolerance and fatigue are common in LC. The aim was to measure the maximal exercise capacity of the LC patients with these symptoms and to analyze whether this capacity was related to heart rate (HR) responses at rest and during exercise and recovery, to find out possible sympathetic overactivity, dysautonomia or chronotropic incompetence.

METHODS: Cardiopulmonary exercise test was conducted on 101 LC patients, who were admitted to exercise testing. The majority of them (86%) had been treated at home during their acute COVID-19 infection. Peak oxygen uptake (VO2peak), maximal power during the last 4 min of exercise (Wlast4), HRs, and other exercise test variables were compared between those with or without subjective exercise intolerance, fatigue, or both.

RESULTS: The measurements were performed in mean 12.7 months (SD 5.75) after COVID-19 infection in patients with exercise intolerance (group EI, 19 patients), fatigue (group F, 31 patients), their combination (group EI + F, 37 patients), or neither (group N, 14 patients). Exercise capacity was, in the mean, normal in all symptom groups and did not significantly differ among them. HRs were higher in group EI + F than in group N at maximum exercise (169/min vs. 158/min, p = 0.034) and 10 min after exercise (104/min vs. 87/min, p = 0.028). Independent of symptoms, 12 patients filled the criteria of dysautonomia associated with slightly decreased Wlast4 (73% vs. 91% of sex, age, height, and weight-based reference values p = 0.017) and 13 filled the criteria of chronotropic incompetence with the lowest Wlast4 (63% vs. 93%, p < 0.001), VO2peak (70% vs. 94%, p < 0.001), the lowest increase of systolic blood pressure (50 mmHg vs. 67 mmHg, p = 0.001), and the greatest prevalence of slight ECG-findings (p = 0.017) compared to patients without these features. The highest prevalence of chronotropic incompetence was seen in the group N (p = 0.022).

CONCLUSIONS: This study on LC patients with different symptoms showed that cardiopulmonary exercise capacity was in mean normal, with increased sympathetic activity in most patients. However, we identified subgroups with dysautonomia or chronotropic incompetence with a lowered exercise capacity as measured by Wlast4 or VO2peak. Subjective exercise intolerance and fatigue poorly foresaw the level of exercise capacity. The results could be used to plan the rehabilitation from LC and for selection of the patients suitable for it.}, } @article {pmid39117891, year = {2024}, author = {Rofail, D and Somersan-Karakaya, S and Mylonakis, E and Choi, JY and Przydzial, K and Marquis, S and Zhao, Y and Hussein, M and Norton, TD and Podolanczuk, AJ and Geba, GP}, title = {The symptoms evolution of long COVID‑19 (SE-LC19): a new patient-reported content valid instrument.}, journal = {Journal of patient-reported outcomes}, volume = {8}, number = {1}, pages = {87}, pmid = {39117891}, issn = {2509-8020}, support = {N/A//Regeneron Pharmaceuticals/ ; HHSO100201700020C//Department of Health and Human Services, Office of the Administration for Strategic Preparedness and Response, and Biomedical Advanced Research and Development Authority/ ; }, mesh = {Humans ; *COVID-19/psychology ; *Patient Reported Outcome Measures ; Female ; Male ; *Psychometrics/methods/instrumentation ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Aged ; Adult ; Reproducibility of Results ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID‑19 (SE-LC19), and establish its content validity.

METHODS: The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID. A 2-part mixed-method approach was employed. Part 1: Qualitative interviews with a purposive sample of 41 patients with confirmed long COVID were conducted for the content validation of SE-LC19. During cognitive debriefing interviews, patients were asked to describe their understanding of the instrument's instructions, specific symptoms, response options, and recall period to ensure its relevance and comprehensiveness. Five clinicians of different medical specialties who regularly treated patients with long COVID were also interviewed to obtain their clinical expert opinions on SE-LC19. Part 2: Exploratory Rasch Measurement Theory (RMT) analysis was conducted to evaluate the psychometric properties of the SE-LC19 data collected during the interviews.

RESULTS: Overall, patients reported that the instructions, questions, recall period, and response options for SE-LC19 were comprehensive and relevant. Minor conceptual gaps reported by patients captured nuances in the experience of some symptoms that could be considered in future studies. Some patients suggested a revision of the recall period from 24 h to 7 days to be able to capture more symptoms given the waxing and waning nature of some symptoms. Clinicians found the instrument comprehensive with minimal suggestions regarding its content. Exploratory RMT analyses provided evidence that the SE-LC19 questionnaire performed as intended.

CONCLUSION: The present mixed-methods study in patients with confirmed long COVID supports the content validity and applicability of the SE-LC19 instrument to evaluate the symptoms of patients with long COVID. Further research is warranted to explore the psychometric properties of the instrument and refine a meaningful and robust patient-relevant endpoint for use in different settings such as clinical trials and clinical practice to track the onset, severity, and recovery of long COVID.}, } @article {pmid39117068, year = {2024}, author = {Sun, G and Lin, K and Ai, J and Zhang, W}, title = {'The efficacy of antivirals, corticosteroids, and mAbs as acute COVID treatments in reducing the incidence of long COVID' - Author's reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {12}, pages = {1618-1619}, doi = {10.1016/j.cmi.2024.07.023}, pmid = {39117068}, issn = {1469-0691}, } @article {pmid39116863, year = {2024}, author = {Carpio-Orantes, LD and Trelles-Hernández, D and García-Méndez, S and Sánchez-Díaz, JS and Aguilar-Silva, A and López-Vargas, ER}, title = {Clinical-epidemiological characterization of patients with long COVID in Mexico.}, journal = {Gaceta medica de Mexico}, volume = {160}, number = {2}, pages = {136-143}, doi = {10.24875/GMM.M24000875}, pmid = {39116863}, issn = {0016-3813}, mesh = {Humans ; Mexico/epidemiology ; *COVID-19/epidemiology ; Female ; Male ; Adult ; Middle Aged ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Young Adult ; Aged ; COVID-19 Vaccines ; Obesity/epidemiology/complications ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Long COVID is defined as the persistence of COVID-19 symptoms four weeks after having undergone acute infection, according to the most recent CDC definition. It is estimated that there are 65 million people affected by this entity, although other figures speak of 200 million.

OBJECTIVE: To characterize the population affected by long COVID in Mexico.

MATERIAL AND METHODS: Patients older than 18 years who agreed to answer an online survey and who met the criteria for long COVID were included.

RESULTS: Data from 203 subjects were included, with 138 (68.0%) being found to be females, and average age to be 41.8 years; 29.6% had severe disease, and 70.4%, mild to moderate disease; 89.7% had received prior COVID-19 vaccination: 6.9% had received one dose; 31.5%, two doses; and 51.2%, three or more doses. The main risk factors were diabetes, overweight or obesity, and hypertension. The most commonly reported symptom was fatigue, followed by other neuropsychiatric manifestations.

CONCLUSION: It is important for the population affected by long COVID to be characterized in order to generate diagnostic and treatment protocols.}, } @article {pmid39116840, year = {2024}, author = {Fessler, SN and Liu, L and Chang, Y and Johnston, CS}, title = {Body Mass Index Is Associated with Post-Acute Elevations in Biomarkers of Platelet Activation and Inflammation in Unvaccinated Adults Diagnosed with COVID-19 in the Previous 8 Weeks.}, journal = {Obesity facts}, volume = {17}, number = {6}, pages = {652-657}, pmid = {39116840}, issn = {1662-4033}, mesh = {Humans ; *COVID-19/blood/complications ; *Body Mass Index ; *Biomarkers/blood ; Male ; Adult ; Female ; *Inflammation/blood ; *Obesity/blood/complications ; Middle Aged ; *Platelet Activation ; SARS-CoV-2 ; Interleukin-6/blood ; Young Adult ; C-Reactive Protein/metabolism ; }, abstract = {INTRODUCTION: Obesity has arisen as a prominent risk factor for COVID-19 severity and long COVID, potentially owed in part to the obesity-induced proinflammatory state. This study aimed to examine relationships among circulating inflammatory biomarkers and body mass index in nonhospitalized adults recently diagnosed with COVID-19.

METHODS: This analysis included participants who completed a randomized placebo-controlled trial conducted in October 2020-March 2021. Participants (19-53 years) were unvaccinated and enrolled following COVID-19 diagnosis as allowed by CDC return-to-work guidance. Anthropometrics and biomarkers were assessed at study baseline and week four. We examined the associations between body mass index (BMI) and inflammatory biomarkers via multiple regression models.

RESULTS: At study baseline (i.e., the point of enrollment following COVID-19 diagnosis) across all participants (N = 60), a higher BMI was associated with elevations in several inflammatory biomarkers including IL-6 (β = 7.63, 95% CI = 3.54, 11.89, p = 0.0004), ferritin (β = 6.31, 95% CI = 1.97, 10.83, p = 0.0047), high sensitivity C-reactive protein (β = 13.1, 95% CI = 8.03, 18.42, p = < 0.0001), tumor necrosis factor-α (β = 3.23, 95% CI = 0.91, 5.60, p = 0.0069), IL-12p40 (β = 3.69, 95% CI = 0.93, 6.52, p = 0.0094), IL-13 (β = 5.11, 95% CI = 1.00, 9.40, p = 0.0154), and IL-1Ra (β = 7.57, 95% CI = 3.61, 11.70, p = 0.0003). In control group participants (n = 30) after 4 weeks, a higher BMI was associated with elevations in IL-4 (β = 17.8, 95% CI = 0.84, 37.6, p = 0.0397) and sP-selectin (β = 1.16, 95% CI = 0.22, 2.11, p = 0.0182), controlling for baseline and covariates.

CONCLUSIONS: Here, BMI was positively associated with circulating biomarkers of platelet activation and inflammation in adults recently diagnosed with COVID-19 after 4 weeks. The shift in post-acute COVID-19 inflammatory biomarkers associated with an increasing BMI noted here shares similarities to biomarkers of LC reported in the literature.}, } @article {pmid39114821, year = {2024}, author = {Paterson, DI and White, JA and Beaulieu, C and Sherrington, R and Prado, CM and Tandon, P and Halloran, K and Smith, S and McCombe, JA and Ritchie, B and Pituskin, E and Haykowsky, MJ and Coulden, R and Emery, D and Tsui, AK and Wu, KY and Oudit, GY and Ezekowitz, JA and Thompson, RB}, title = {Rationale and design of the multi organ inflammation with serial testing study: a comprehensive assessment of functional and structural abnormalities in patients with recovered COVID-19.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1392169}, pmid = {39114821}, issn = {2296-858X}, abstract = {INTRODUCTION: Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15-20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear.

METHODS: A multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3-6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized.

DISCUSSION: Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease.

STUDY REGISTRATION: clinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).}, } @article {pmid39114613, year = {2024}, author = {Kinugasa, Y and Llamas-Covarrubias, MA and Ozaki, K and Fujimura, Y and Ohashi, T and Fukuda, K and Higashiue, S and Nakamura, Y and Imai, Y}, title = {Author's Response to Letter to the Editor: "A Deep Dive into Japan's State of Emergency: How Political Decisions Affected Post-COVID-19 Syndrome".}, journal = {JMA journal}, volume = {7}, number = {3}, pages = {455-456}, pmid = {39114613}, issn = {2433-3298}, } @article {pmid39111695, year = {2024}, author = {Datta, BK and Phillips, S}, title = {Long COVID and the Higher Risk of Food Insecurity Among Participants and Nonparticipants of Food Assistance Programs in the United States.}, journal = {Journal of the Academy of Nutrition and Dietetics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jand.2024.07.171}, pmid = {39111695}, issn = {2212-2672}, abstract = {BACKGROUND: In the aftermath of the COVID-19 public health emergency, it is important to understand the extent of socioeconomic burdens of long COVID, defined as continuation of symptoms after initial infection, including food insecurity.

OBJECTIVE: This study aimed to assess the association between long COVID and family food insecurity among low-income individuals (or any of their family members living with them) who were participants and nonparticipants in public food assistance programs (Supplemental Nutrition Assistance Program [SNAP], Special Supplemental Nutrition Program for Women, Infants, and Children [WIC], and National School Lunch Program [NSLP]) in the United States.

DESIGN: The study used an observational cross-sectional design.

PARTICIPANTS/SETTING: Data on 7151 adults (aged 18+ years), with family income of < 200% of the Federal Poverty line, from the 2022 National Health Interview Survey, were analyzed.

MAIN OUTCOME MEASURES: Level of family food security, based on responses to a set of 10 questions measuring family's food security during the past 30 days.

Multinomial logistic regression models were estimated to obtain relative risk ratios of marginal and low/very low food security, relative to the base outcome of high food security, for long COVID status. Multivariable models were estimated separately for the full sample and for subgroups of food assistance participants and nonparticipants. A seemingly unrelated regression (SUR) specification was estimated to assess whether the estimates were different across the participant and nonparticipant subgroups.

RESULTS: Compared with individuals who never had COVID-19, the adjusted relative risks of experiencing marginal and low/very low food security were 1.42 (95% CI, 1.00-2.02) and 1.43 (95% CI, 1.08-1.91) times higher, respectively, for individuals who had long COVID. Although the adjusted risks were not observed to be statistically significant in the participant subgroup, among nonparticipants, adjusted relative risk ratios were 2.34 (95% CI, 1.43-3.82) and 1.56 (95% CI, 1.02-2.39), respectively. SUR results showed that relationships between long COVID and food insecurity were only different for marginal and not low/very low levels of food security between food assistance participant and nonparticipant groups.

CONCLUSIONS: Study findings highlight a significantly higher risk of marginal and low/very low- food security among low-income adults who had long COVID, especially those who were nonparticipants in public food assistance programs. Further research is warranted to explore the causal pathways of this relationship for informing policies to mitigate the burden of long COVID.}, } @article {pmid39109239, year = {2024}, author = {Buzaglo, AV and Vieira, CMAG and Ciurleo, GCV and Belayev, L and Oriá, RB}, title = {Do APOE4, malnutrition, and long COVID-19 compound the risk factors for stroke in adverse environments?.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1422218}, pmid = {39109239}, issn = {2296-861X}, } @article {pmid39106653, year = {2024}, author = {Tang, X and Hou, K and Chen, X and Fan, W and Wu, H and Lu, C and He, GX}, title = {Discovery of macrocyclic covalent inhibitors for severe acute respiratory syndrome coronavirus 2 3CL protease.}, journal = {Bioorganic & medicinal chemistry}, volume = {111}, number = {}, pages = {117846}, doi = {10.1016/j.bmc.2024.117846}, pmid = {39106653}, issn = {1464-3391}, mesh = {*Coronavirus 3C Proteases/antagonists & inhibitors/metabolism ; Humans ; *SARS-CoV-2/drug effects ; *Macrocyclic Compounds/chemistry/pharmacology/chemical synthesis/pharmacokinetics ; *Antiviral Agents/pharmacology/chemistry/chemical synthesis/pharmacokinetics ; Microsomes, Liver/metabolism ; Peptidomimetics/pharmacology/chemistry/chemical synthesis ; Drug Discovery ; COVID-19 Drug Treatment ; Protease Inhibitors/pharmacology/chemistry/chemical synthesis/pharmacokinetics ; Structure-Activity Relationship ; }, abstract = {The coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spread worldwide for more than 3 years. Although the hospitalization rate and mortality have decreased dramatically due to wide vaccination effort and improved treatment options, the disease is still a global health issue due to constant viral mutations, causing negative impact on social and economic activities. In addition, long COVID and complications arising from COVID-19 weeks after infection have become a concern for public health experts. Therefore, better treatments for COVID-19 are still needed. Herein, we describe a class of macrocyclic peptidomimetic compounds that are potent inhibitors of SARS-Cov-2 3CL protease (3CL[pro]). Significantly, some of the compounds showed a higher stability against human liver microsomes (HLM t1/2 > 180 min) and may be suitable for oral administration without the need for a pharmacokinetic (PK) boosting agent such as ritonavir.}, } @article {pmid39106427, year = {2024}, author = {Docampo, MJ and Batruch, M and Oldrati, P and Berenjeno-Correa, E and Hilty, M and Leventhal, G and Lutterotti, A and Martin, R and Sospedra, M}, title = {Clinical and Immunologic Effects of Paraprobiotics in Long-COVID Patients: A Pilot Study.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {11}, number = {5}, pages = {e200296}, pmid = {39106427}, issn = {2332-7812}, mesh = {Humans ; Pilot Projects ; Male ; *COVID-19/immunology/complications/therapy ; *Probiotics/pharmacology/administration & dosage ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; *Gastrointestinal Microbiome ; Adult ; Quality of Life ; }, abstract = {BACKGROUND AND OBJECTIVES: After the enormous health burden during the acute stages of the COVID-19 pandemic, we are now facing another important challenge, that is, long-COVID, a clinical condition with often disabling signs and symptoms of the neuropsychiatric, gastrointestinal, respiratory, cardiovascular, and immune systems. While the pathogenesis of this syndrome is still poorly understood, alterations of immune function and the gut microbiota seem to play important roles. Because affected individuals are frequently unable to work for prolonged periods and suffer numerous health compromises, effective treatments represent a major unmet medical need. Multiple potential therapies have been tried, but none is approved yet. Approaches that are able to influence the immune system and gut microbiota such as probiotics and paraprobiotics, i.e., nonviable probiotics, seem promising candidates. We, therefore, evaluated the clinical and immunologic effects of paraprobiotics in a small pilot study.

METHODS: A total of 6 patients with long-COVID were followed systematically for more than 12 months after disease onset using standardized validated questionnaires, a smartphone app, and wearable sensors to assess neurocognitive function, fatigue, depressiveness, autonomic nervous system alterations, and quality of life. We then offered patients defined paraprobiotics for 4 weeks and evaluated them at the end of the treatment period using the same questionnaires, smartphone app, and wearable sensors. In addition, a comprehensive immunophenotyping and gut microbiota analysis was performed before and after treatment.

RESULTS: Improvements in several of the neurologic symptoms such as dysautonomia, fatigue, and depression were documented using both patient-reported outcomes and data from the smartphone app and wearable sensors. Of interest, the expression of activation markers on some immune cell populations such as B cells and nonclassical monocytes and the expression of toll-like receptor 2 (TLR2) on T cells were reduced after paraprobiotics treatment.

DISCUSSION: Our results suggest that paraprobiotics might exert positive effects in patients with long-COVID most likely by modulating immune cell activation and expression of TLR2 on T cells. Further studies with paraprobiotics should confirm the promising observations of this small pilot study and hopefully not only improve the outcome of long-COVID but also unravel the pathomechanisms of this condition.

CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that paraprobiotics increase the probability of favorable changes of clinical and immunologic markers in patients with long-COVID.}, } @article {pmid39106232, year = {2024}, author = {Segneri, L and Babina, N and Hammerschmidt, T and Fronzetti Colladon, A and Gloor, PA}, title = {Too much focus on your health might be bad for your health: Reddit user's communication style predicts their Long COVID likelihood.}, journal = {PloS one}, volume = {19}, number = {8}, pages = {e0308340}, pmid = {39106232}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Social Media ; *Communication ; Female ; SARS-CoV-2/isolation & purification ; Male ; Adult ; Risk Factors ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long Covid is a chronic disease that affects more than 65 million people worldwide, characterized by a wide range of persistent symptoms following a Covid-19 infection. Previous studies have investigated potential risk factors contributing to elevated vulnerability to Long Covid. However, research on the social traits associated with affected patients is scarce. This study introduces an innovative methodological approach that allows us to extract valuable insights directly from patients' voices. By analyzing written texts shared on social media platforms, we aim to collect information on the psychological aspects of people who report experiencing Long Covid. In particular, we collect texts of patients they wrote BEFORE they were afflicted with Long Covid. We examined the differences in communication style, sentiment, language complexity, and psychological factors of natural language use among the profiles of 6.107 Reddit users, distinguishing between those who claim they have never contracted Covid -19, those who claim to have had it, and those who claim to have experienced Long Covid symptoms. Our findings reveal that people in the Long Covid group frequently discussed health-related topics before the pandemic, indicating a greater focus on health-related concerns. Furthermore, they exhibited a more limited network of connections, lower linguistic complexity, and a greater propensity to employ emotionally charged expressions than the other groups. Using social media data, we can provide a unique opportunity to explore potential risk factors associated with Long Covid, starting from the patient's perspective.}, } @article {pmid39106091, year = {2024}, author = {Thomas, B and Pattinson, R and Bundy, C and Davies, JL}, title = {Somatosensory processing in long COVID fatigue and its relations with physiological and psychological factors.}, journal = {Experimental physiology}, volume = {109}, number = {10}, pages = {1637-1649}, pmid = {39106091}, issn = {1469-445X}, support = {HS 22 33/HCRW/HCRW_/United Kingdom ; HS 22 33/HCRW/HCRW_/United Kingdom ; }, mesh = {Humans ; *COVID-19/physiopathology/psychology ; *Fatigue/physiopathology/psychology ; Male ; Female ; Adult ; Middle Aged ; Affect/physiology ; Autonomic Nervous System/physiopathology ; SARS-CoV-2 ; Physical Exertion/physiology ; }, abstract = {Fatigue is prevalent amongst people with long COVID, but is poorly understood. The sensory attenuation framework proposes that impairments in sensory processing lead to heightened perception of effort, driving fatigue. This study aims to investigate the role of somatosensory processing impairments in long COVID fatigue and quantify how sensory processing relates to other prominent symptoms of long COVID including autonomic dysfunction, mood and illness beliefs in driving the experience of fatigue. We will recruit 44 individuals with long COVID fatigue and 44 individuals with neither long COVID nor fatigue (controls). Our primary objective is to compare baseline somatosensory processing between individuals with long COVID fatigue and controls. Additionally, we will explore the associations between somatosensory processing, fatigability and the level of fatigue induced by cognitive and physical exertion. Due to the complex nature of fatigue, we will also investigate how long COVID, state fatigue, perceived effort, mood, illness beliefs, autonomic symptoms and autonomic nervous system function interact to predict trait fatigue. This comprehensive investigation aims to elucidate how sensory processing and other prominent symptoms interact to impact the experience of fatigue.}, } @article {pmid39105048, year = {2024}, author = {Milic, G and Ristic, M and Milosevic, M and Mitovic, N and Dimitrijevic, L and Jesic Petrovic, T and Salovic, B}, title = {Post-COVID-19 Syndrome Associated With Multiple Autoimmune Diseases (DM I-LADA, Chronic Autoimmune Thyroiditis and Pernicious Anemia): Case Report.}, journal = {Clinical medicine insights. Endocrinology and diabetes}, volume = {17}, number = {}, pages = {11795514241267185}, pmid = {39105048}, issn = {1179-5514}, abstract = {COVID-19, a global epidemic of infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only initially refers to acute manifestations but also chronic symptoms known as Long COVID-19. Long COVID-19 represents a significant burden to healthcare systems worldwide. This syndrome encompasses a wide range of continuing health problems with variable durations and consequences for patients' everyday lives. A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc., but with unclear evidence of associated disease occurrence. We present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection.}, } @article {pmid39103842, year = {2024}, author = {Han, T and Dai, C and Liang, Y and Lin, X and Gao, M and Liu, X and Wu, X and Lu, Y and Xi, X and Tian, F and Zhao, C and Sun, X and Yuan, H}, title = {PFC/M1 activation and excitability: a longitudinal cohort study on fatigue symptoms in healthcare workers post-COVID-19.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {720}, pmid = {39103842}, issn = {1479-5876}, support = {82272591//National Natural Science Foundation of China/ ; 82072534//National Natural Science Foundation of China/ ; XJZT23XG35;XJZT23XG46//Clinical Research Program on COVID-19 of Xijing Hospital in 2023/ ; XJZT24JC19//Medical Staff Training & Boost Project of Xijing Hospital/ ; XJZT24LY11//Medical Staff Training & Boost Project of Xijing Hospital/ ; XJZT24QN20//Medical Staff Training & Boost Project of Xijing Hospital/ ; }, mesh = {Humans ; *COVID-19/physiopathology ; *Fatigue/physiopathology ; Male ; *Health Personnel ; Female ; Longitudinal Studies ; Adult ; *Prefrontal Cortex/physiopathology/diagnostic imaging ; *Transcranial Magnetic Stimulation ; *Motor Cortex/physiopathology ; Middle Aged ; SARS-CoV-2/isolation & purification ; Prospective Studies ; Spectroscopy, Near-Infrared ; Cohort Studies ; }, abstract = {BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection.

METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course.

RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients.

CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation.

TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.}, } @article {pmid39103829, year = {2024}, author = {Low, EV and Pathmanathan, MD and Ten, YY and Chidambaram, SK and Kim, WR and Lee, WJ and Teh, ZW and Appannan, MR and Ismail, M and Samad, AA and Peariasamy, KM}, title = {Nirmatrelvir/ritonavir treatment and the risk of post-COVID condition over 180 days in Malaysia.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {780}, pmid = {39103829}, issn = {1471-2334}, support = {NIH/800-3/2/2 Jilid 13 (182)//Ministry of Health Malaysia Research Grant/ ; }, mesh = {Humans ; *Ritonavir/therapeutic use ; Male ; Female ; Adult ; Retrospective Studies ; Middle Aged ; *Quality of Life ; Malaysia/epidemiology ; *COVID-19 Drug Treatment ; COVID-19/prevention & control ; SARS-CoV-2 ; Aged ; Antiviral Agents/therapeutic use ; }, abstract = {BACKGROUND: The effect of nirmatrelvir/ritonavir on preventing post-COVID condition (PCC) in the BA4, BA5, and XBB Omicron predominant periods is not well understood. The purpose of this study was to assess how nirmatrelvir/ritonavir treatment affected both PCC and health-related quality of life.

METHODS: This retrospective cohort study enrolled 2,524 adults aged 18 years and older who were eligible for nirmatrelvir/ritonavir between July 14 to November 14, 2022. All outcomes were observed from the patient's first visit to the primary health clinic, 1 week, 1 month, 3 months, and 6 months after testing positive for COVID-19. The primary outcome was the presence of PCC. Secondary outcomes included the effects on health-related quality of life, such as walking, bathing and dressing, activities, cause adverse emotions or signs that prevent individuals from leading normal lives over a 180-day observation period.

RESULTS: There were no significant differences observed between the nirmatrelvir/ritonavir and those not administered (control group) in terms of PCC symptoms at 3 months (OR 0.71 95% CI 0.31, 1.64) and 6 months (OR 1.30 95% CI 0.76, 2.21). At 3 months, the use of nirmatrelvir/ritonavir was associated with a 26% reduction in symptoms causing negative emotions (OR 0.74 95% CI 0.60, 0.92) and an increased likelihood of symptoms limiting walking (OR 1.58 95% CI 1.10, 2.27). However, there were no significant differences between the nirmatrelvir/ritonavir and the control group in terms of the impact of PCC on health-related quality of life at 6 months.

CONCLUSIONS: Our study indicates that the administration of nirmatrelvir/ritonavir does not significantly reduce PCC after 3 months and 6 months in a population with high vaccination coverage.}, } @article {pmid39103645, year = {2024}, author = {Thomas, C and Faghy, MA and Chidley, C and Phillips, BE and Bewick, T and Ashton, RE}, title = {Blood Biomarkers of Long COVID: A Systematic Review.}, journal = {Molecular diagnosis & therapy}, volume = {28}, number = {5}, pages = {537-574}, pmid = {39103645}, issn = {1179-2000}, mesh = {Humans ; *COVID-19/blood/diagnosis ; *Biomarkers/blood ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition.

Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were ≥ 18 years old and group sizes ≥ 10 participants, and were compared against a control group without any known co-morbidities.

METHODS: A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies.

RESULTS: A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities.

DISCUSSION AND CONCLUSIONS: Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.}, } @article {pmid39102426, year = {2024}, author = {Li, H and Wan, L and Liu, M and Ma, E and Huang, L and Yang, Y and Li, Q and Fang, Y and Li, J and Han, B and Zhang, C and Sun, L and Hou, X and Li, H and Sun, M and Qian, S and Duan, X and Zhao, R and Yang, X and Chen, Y and Wu, S and Zhang, X and Zhang, Y and Cheng, G and Chen, G and Gao, Q and Xu, J and Hou, L and Wei, C and Zhong, H}, title = {SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.}, journal = {PLoS pathogens}, volume = {20}, number = {8}, pages = {e1012291}, pmid = {39102426}, issn = {1553-7374}, mesh = {*Heart Failure/metabolism/virology ; *SARS-CoV-2 ; Animals ; *Giant Cells/virology/metabolism/pathology ; *COVID-19/metabolism/complications/virology/pathology ; Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; Mice ; *Cellular Senescence ; Extracellular Vesicles/metabolism ; }, abstract = {SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.}, } @article {pmid39102196, year = {2024}, author = {Fuller, H and King-Okoye, M}, title = {Improving Pathways to Care for Ethnic Minority Communities.}, journal = {Advances in experimental medicine and biology}, volume = {1458}, number = {}, pages = {157-173}, pmid = {39102196}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control/therapy ; COVID-19 Vaccines/therapeutic use ; *Ethnic and Racial Minorities ; *Health Services Accessibility ; *Healthcare Disparities ; Pandemics/prevention & control ; *Social Determinants of Health ; }, abstract = {It is well established that the COVID-19 pandemic has had a substantial impact on ethnic minority communities and has worsened existing health inequalities experienced by these populations globally. Individuals from ethnic minority backgrounds have not only been more likely to become infected with COVID-19 throughout the pandemic, but they have also higher risk of adverse symptoms and death following infection. Factors responsible for these discrepancies are wide reaching and encompass all aspects of the social determinants of health (SDoH). Although always an area of concern among healthcare professionals, barriers to health care experienced by ethnic minority populations became a more pertinent issue during the COVID-19 pandemic when all individuals required sufficient and sustained access to a healthcare system (whether this be for COVID-19 testing, vaccination or treatment). These healthcare barriers exacerbated the increased COVID-19 burden experienced by minority populations and will continue to detrimentally impact the health of these populations during future COVID-19 waves or indeed, future novel pandemics. This chapter aims to summarise the major healthcare barriers experienced by minority populations throughout the COVID-19 pandemic, including COVID-19 prevention, vaccine rollout, care during hospitalisation and post-COVID care for long COVID patients. To end, this chapter will summarise lessons learned and future directions that need to be taken to improve health disparities and healthcare access for minority populations in relation to the COVID pandemic and beyond.}, } @article {pmid39102189, year = {2024}, author = {Sher, L}, title = {Long COVID-19 and Suicide.}, journal = {Advances in experimental medicine and biology}, volume = {1458}, number = {}, pages = {51-57}, pmid = {39102189}, issn = {0065-2598}, mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Suicide/psychology/statistics & numerical data ; *SARS-CoV-2/pathogenicity ; Suicidal Ideation ; Risk Factors ; Suicide Prevention ; Post-Acute COVID-19 Syndrome ; Depression/psychology/epidemiology ; Anxiety/psychology/epidemiology ; Mental Disorders/psychology/epidemiology ; }, abstract = {Suicide is a significant public health problem around the world. More than 90% of individuals who die by suicide have a diagnosable psychiatric disorder, and most persons who attempt suicide also have a psychiatric illness. Depression, anxiety, posttraumatic symptoms, sleep disturbances, decreased energy, and cognitive abnormalities are the most frequently reported psychiatric symptoms of long COVID. All these conditions are associated with suicidal ideation and behavior. Therefore, individuals with long COVID may be at increased risk of suicide. Recent studies of patients with long COVID confirm that individuals with long COVID are at increased suicide risk. It is vital to educate clinicians taking care of long COVID individuals that patients with long COVID may be suicidal, that it is essential to screen patients with long COVID for suicidality, and if needed, suicide prevention interventions should be employed.}, } @article {pmid39100241, year = {2024}, author = {Azambuja, P and Bastos, LSL and Batista-da-Silva, AA and Ramos, GV and Kurtz, P and Dias, CMC and da Silva, EP and Arouca, LE and Soares, J and Sejvar, JJ and Sigfrid, L and Ranzani, OT and Hamacher, S and Bozza, FA}, title = {Prevalence, risk factors, and impact of long COVID in a socially vulnerable community in Brazil: a prospective cohort study.}, journal = {Lancet regional health. Americas}, volume = {37}, number = {}, pages = {100839}, pmid = {39100241}, issn = {2667-193X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Long COVID is an emerging global public health issue. Socially vulnerable communities in low- and-middle-income countries were severely impacted by the pandemic and are underrepresented in research. This prospective study aimed to determine the prevalence of long COVID, its impact on health, and associated risk factors in one such community in Rio de Janeiro, Brazil.

METHODS: A total of 710 individuals aged 18 and older, with confirmed SARS-CoV-2 infection at least three months prior, were enrolled between November 25, 2021, and May 5, 2022. Participants were assessed via telephone or in person using a standardized questionnaire to evaluate their perception of recovery, symptoms, quality of life, and functional status.

FINDINGS: Twenty percent of participants did not feel fully recovered, 22% experienced new or persistent symptoms, 26% had worsened functional status, 18% had increased dyspnoea, and 32% reported a worse quality of life. Persistent symptoms included headache, cough, fatigue, muscle pain, and shortness of breath. Dyspnoea during the acute phase was the strongest independent predictor of worsening outcomes. Females and individuals with comorbidities were more likely to report worse recovery, functioning, dyspnoea, and quality of life.

INTERPRETATION: Our findings reveal a high burden of severe and persistent physical and mental health sequelae in a socially vulnerable community following COVID-19.

FUNDING: UK Foreign, Commonwealth and Development Office and Wellcome Trust Grant (222048/Z/20/Z), Fundação Oswaldo Cruz (FIOCRUZ), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the Centers for Disease Control and Prevention (CDC).}, } @article {pmid39100135, year = {2024}, author = {Khoja, O and Silva-Passadouro, B and Cristescu, E and McEwan, K and Doherty, D and O'Connell, F and Ponchel, F and Mulvey, M and Astill, S and Tan, AL and Sivan, M}, title = {Clinical Characterization of New-Onset Chronic Musculoskeletal Pain in Long COVID: A Cross-Sectional Study.}, journal = {Journal of pain research}, volume = {17}, number = {}, pages = {2531-2550}, pmid = {39100135}, issn = {1178-7090}, abstract = {PURPOSE: New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life.

PATIENTS AND METHODS: Thirty adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire-short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L).

RESULTS: New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro-inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores.

CONCLUSION: New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.}, } @article {pmid39100091, year = {2024}, author = {Xian, SP and Li, ZY and Li, W and Yang, PF and Huang, SH and Liu, Y and Tang, L and Lai, J and Zeng, FM and He, JZ and Liu, Y}, title = {Spatial immune landscapes of SARS-CoV-2 gastrointestinal infection: macrophages contribute to local tissue inflammation and gastrointestinal symptoms.}, journal = {Frontiers in cell and developmental biology}, volume = {12}, number = {}, pages = {1375354}, pmid = {39100091}, issn = {2296-634X}, abstract = {BACKGROUND: In some patients, persistent gastrointestinal symptoms like abdominal pain, nausea, and diarrhea occur as part of long COVID-19 syndrome following acute respiratory symptoms caused by SARS-CoV-2. However, the characteristics of immune cells in the gastrointestinal tract of COVID-19 patients and their association with these symptoms remain unclear.

METHODOLOGY: Data were collected from 95 COVID-19 patients. Among this cohort, 11 patients who exhibited gastrointestinal symptoms and underwent gastroscopy were selected. Using imaging mass cytometry, the gastrointestinal tissues of these patients were thoroughly analyzed to identify immune cell subgroups and investigate their spatial distribution.

RESULTS: Significant acute inflammatory responses were found in the gastrointestinal tissues, particularly in the duodenum, of COVID-19 patients. These alterations included an increase in the levels of CD68[+] macrophages and CD3[+]CD4[+] T-cells, which was more pronounced in tissues with nucleocapsid protein (NP). The amount of CD68[+] macrophages positively correlates with the number of CD3[+]CD4[+] T-cells (R = 0.783, p < 0.001), additionally, spatial neighborhood analysis uncovered decreased interactions between CD68[+] macrophages and multiple immune cells were noted in NP-positive tissues. Furthermore, weighted gene coexpression network analysis was employed to extract gene signatures related to clinical features and immune responses from the RNA-seq data derived from gastrointestinal tissues from COVID-19 patients, and we validated that the MEgreen module shown positive correlation with clinical parameter (i.e., Total bilirubin, ALT, AST) and macrophages (R = 0.84, p = 0.001), but negatively correlated with CD4[+] T cells (R = -0.62, p = 0.004). By contrast, the MEblue module was inversely associated with macrophages and positively related with CD4[+] T cells. Gene function enrichment analyses revealed that the MEgreen module is closely associated with biological processes such as immune response activation, signal transduction, and chemotaxis regulation, indicating its role in the gastrointestinal inflammatory response.

CONCLUSION: The findings of this study highlight the role of specific immune cell groups in the gastrointestinal inflammatory response in COVID-19 patients. Gene coexpression network analysis further emphasized the importance of the gene modules in gastrointestinal immune responses, providing potential molecular targets for the treatment of COVID-19-related gastrointestinal symptoms.}, } @article {pmid39099965, year = {2024}, author = {Mdivnishvili, M and Mdinaradze, D and Virkovi, K and Gogashvili, G}, title = {A Case Report of Long COVID or Post-COVID-19 Symptoms and Characteristics.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e63876}, pmid = {39099965}, issn = {2168-8184}, abstract = {The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global health crisis. Long COVID refers to a debilitating condition characterized by severe symptoms that may arise after the initial acute phase of COVID-19. Significant attention has been directed toward the acute phase of the respiratory system while overshadowing the understanding and management of long-term complications, often referred to as "long COVID." This case focuses on a 19-year-old female who experienced the multisystemic manifestation of COVID-19 syndrome several months after the initial infection, spanning cardiovascular, respiratory, endocrine, central nervous system, and multi-skeletal domains. This study aims to describe the patient's experience and recovery process with a specific emphasis on the long COVID experience.}, } @article {pmid39099786, year = {2024}, author = {Lam, WC and Wei, D and Li, H and Yao, L and Zhang, S and Lai, MXY and Zheng, Y and Yeung, JWF and Lau, AYL and Lyu, A and Bian, Z and Cheung, AM and Zhong, LLD}, title = {The use of acupuncture for addressing neurological and neuropsychiatric symptoms in patients with long COVID: a systematic review and meta-analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1406475}, pmid = {39099786}, issn = {1664-2295}, abstract = {IMPORTANCE: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID.

OBJECTIVE: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients.

DATA SOURCES: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers.

STUDY SELECTION: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included.

DATA EXTRACTION AND SYNTHESIS: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I[2]. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940).

MAIN OUTCOMES AND MEASURES: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia.

RESULTS: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01).

CONCLUSION AND RELEVANCE: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms.

PROSPERO, identifier [CRD42022354940].}, } @article {pmid39099780, year = {2024}, author = {Jose, C and Rudroff, T and Chamard-Witkowski, L}, title = {Editorial: The NeuroCOVID-19 syndrome: cognitive and psychological profiles, physiopathology, and impact on neurologically vulnerable populations.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1452895}, pmid = {39099780}, issn = {1664-2295}, } @article {pmid39098684, year = {2024}, author = {Pawar, P and Akolkar, K and Saxena, V}, title = {An integrated bioinformatics approach reveals the potential role of microRNA-30b-5p and let-7a-5p during SARS CoV-2 spike-1 mediated neuroinflammation.}, journal = {International journal of biological macromolecules}, volume = {277}, number = {Pt 4}, pages = {134329}, doi = {10.1016/j.ijbiomac.2024.134329}, pmid = {39098684}, issn = {1879-0003}, mesh = {Humans ; Computational Biology/methods ; COVID-19/genetics/virology ; Cytokines/metabolism/genetics ; Gene Expression Regulation/drug effects ; Gene Regulatory Networks/drug effects ; Microglia/metabolism/drug effects ; *MicroRNAs/genetics/metabolism ; Neuroinflammatory Diseases/genetics ; Protein Interaction Maps ; *SARS-CoV-2/chemistry/physiology ; Signal Transduction/drug effects ; *Spike Glycoprotein, Coronavirus/genetics/metabolism ; }, abstract = {SARS-CoV-2 induced neuroinflammation contributing to neurological sequelae is one of the critical outcomes of long-COVID, however underlying regulatory mechanisms involved therein are poorly understood. We deciphered the profile of dysregulated microRNAs, their targets, associated pathways, protein-protein interactions (PPI), transcription factor-hub genes interaction networks, hub genes-microRNA co-regulatory networks in SARS-CoV-2 Spike-1 (S1) stimulated microglial cells along with candidate drug prediction using RNA-sequencing and multiple bioinformatics approaches. We identified 11 dysregulated microRNAs in the S1-stimulated microglial cells (p < 0.05). KEGG analysis revealed involvement of important neuroinflammatory pathways such as MAPK signalling, PI3K-AKT signalling, Ras signalling and axon guidance. PPI analysis further identified 11 hub genes involved in these pathways. Real time PCR validation confirmed a significant upregulation of microRNA-30b-5p and let-7a-5p; proinflammatory cytokines- IL-6, TNF-α, IL-1β, GM-CSF; and inflammatory genes- PIK3CA and AKT in the S1-stimulated microglial cells, while PTEN and SHIP1 expression was decreased as compared to the non-stimulated cells. Drug prediction analysis further indicated resveratrol, diclofenac and rapamycin as the potential drugs based on their degree of interaction with hub genes. Thus, targeting of these microRNAs and/or their intermediate signalling molecules would be a prospective immunotherapeutic approach in alleviating SARS-CoV-2-S1 mediated neuroinflammation; and needs further investigations.}, } @article {pmid39098596, year = {2024}, author = {Strongin, SR and Stelson, E and Soares, L and Sukhatme, V and Dasher, P and Schito, M and Challa, AP and Geng, LN and Walker, TA}, title = {Using real-world data to accelerate the search for long COVID therapies.}, journal = {Life sciences}, volume = {353}, number = {}, pages = {122940}, doi = {10.1016/j.lfs.2024.122940}, pmid = {39098596}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Clinical Trials as Topic ; Quality of Life ; }, abstract = {Long COVID, a spectrum of symptoms and syndromes that can develop after SARS-COV-2 infection, can significantly affect patients' health, quality of life and impact their ability to productively function in society. There is currently no approved therapy for Long COVID and there is an urgent need for rigorous clinical trials to find such treatments. Although research into the pathophysiology of Long COVID is advancing, investigations into treatment for patients remain underfunded and, as a result, understudied. Owing to the urgency of the Long COVID pandemic and as a research collaborative across a diversity of biomedical innovation value propositions, we are calling for a new approach that parallelizes pathophysiologic and therapeutic research into this condition, leveraging patient-centered research and real-world data to generate hypotheses to assess the effectiveness of existing FDA approved drugs. Accelerated discovery of therapeutics for Long COVID can then be confirmed through efficient and cost-effective adaptive platform clinical trials.}, } @article {pmid39097692, year = {2024}, author = {Ye, L and Zhang, F and Wang, L and Chen, Y and Shi, J and Cai, T}, title = {Identification of the risk factors for insomnia in nurses with long COVID-19.}, journal = {BMC nursing}, volume = {23}, number = {1}, pages = {532}, pmid = {39097692}, issn = {1472-6955}, support = {Y202043652//The General Research Project of Zhejiang Provincial Department of Education/ ; }, abstract = {PURPOSE: To investigate the prevalence of insomnia among nurses with long COVID-19, analyze the potential risk factors and establish a nomogram model.

METHODS: Nurses in Ningbo, China, were recruited for this study. General demographic information and insomnia, burnout, and stress assessment scores were collected through a face-to face questionnaire survey administered at a single center from March to May 2023. We used LASSO regression to identify potential factors contributing to insomnia. Then, a nomogram was plotted based on the model chosen to visualize the results and evaluated by receiver operating characteristic curves and calibration curves.

RESULTS: A total of 437 nurses were recruited. 54% of the nurses had insomnia according to the Insomnia Severity Index (ISI) score. Eleven variables, including family structure, years of work experience, relaxation time, respiratory system sequelae, nervous system sequelae, others sequelae, attitudes toward COVID-19, sleep duration before infection, previous sleep problems, stress, and job burnout, were independently associated with insomnia. The R-squared value was 0.464, and the area under the curve was 0.866. The derived nomogram showed that neurological sequelae, stress, job burnout, sleep duration before infection, and previous sleep problems contributed the most to insomnia. The calibration curves showed significant agreement between the nomogram models and actual observations.

CONCLUSION: This study focused on insomnia among nurses with long COVID-19 and identified eleven risk factors related to nurses' insomnia. A nomogram model was established to illustrate and visualize these factors, which will be instrumental in future research for identifying nurses with insomnia amid pandemic normalization and may increase awareness of the health status of healthcare workers with long COVID-19.}, } @article {pmid39096931, year = {2024}, author = {Taquet, M and Skorniewska, Z and De Deyn, T and Hampshire, A and Trender, WR and Hellyer, PJ and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Raman, B and Leavy, OC and Richardson, M and Elneima, O and McAuley, HJC and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Rogers, N and Houchen-Wolloff, L and Greening, NJ and Mansoori, P and Harrison, EM and Docherty, AB and Lone, NI and Quint, J and Brightling, CE and Wain, LV and Evans, RA and Geddes, JR and Harrison, PJ and , }, title = {Cognitive and psychiatric symptom trajectories 2-3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK.}, journal = {The lancet. Psychiatry}, volume = {11}, number = {9}, pages = {696-708}, doi = {10.1016/S2215-0366(24)00214-1}, pmid = {39096931}, issn = {2215-0374}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Male ; United Kingdom/epidemiology ; Middle Aged ; Longitudinal Studies ; Prospective Studies ; *Hospitalization/statistics & numerical data ; Adult ; Cognitive Dysfunction/epidemiology/psychology/etiology ; Aged ; Depression/epidemiology/psychology ; SARS-CoV-2 ; Cognition ; Anxiety/psychology/epidemiology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning.

METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study.

FINDINGS: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20).

INTERPRETATION: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19.

FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.}, } @article {pmid39096925, year = {2024}, author = {Greenhalgh, T and Sivan, M and Perlowski, A and Nikolich, JŽ}, title = {Long COVID: a clinical update.}, journal = {Lancet (London, England)}, volume = {404}, number = {10453}, pages = {707-724}, doi = {10.1016/S0140-6736(24)01136-X}, pmid = {39096925}, issn = {1474-547X}, mesh = {Humans ; *COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/therapy ; }, abstract = {Post-COVID-19 condition (also known as long COVID) is generally defined as symptoms persisting for 3 months or more after acute COVID-19. Long COVID can affect multiple organ systems and lead to severe and protracted impairment of function as a result of organ damage. The burden of this disease, both on the individual and on health systems and national economies, is high. In this interdisciplinary Review, with a coauthor with lived experience of severe long COVID, we sought to bring together multiple streams of literature on the epidemiology, pathophysiology (including the hypothesised mechanisms of organ damage), lived experience and clinical manifestations, and clinical investigation and management of long COVID. Although current approaches to long COVID care are largely symptomatic and supportive, recent advances in clinical phenotyping, deep molecular profiling, and biomarker identification might herald a more mechanism-informed and personally tailored approach to clinical care. We also cover the organisation of services for long COVID, approaches to preventing long COVID, and suggestions for future research.}, } @article {pmid39094376, year = {2024}, author = {González-Vides, L and Hernández-Verdejo, JL and Gómez-Pedrero, JA and Ruiz-Pomeda, A and Cañadas-Suárez, P}, title = {Oculomotor Behaviour in Individuals with Long COVID-19.}, journal = {Clinical rehabilitation}, volume = {38}, number = {10}, pages = {1372-1381}, doi = {10.1177/02692155241265886}, pmid = {39094376}, issn = {1477-0873}, mesh = {Humans ; *COVID-19 ; Male ; Female ; Middle Aged ; Case-Control Studies ; *Eye Movements/physiology ; *SARS-CoV-2 ; Adult ; Eye-Tracking Technology ; Fixation, Ocular/physiology ; Aged ; Pandemics ; Spain ; }, abstract = {OBJECTIVE: To determine, the impact of long COVID-19 on oculomotor behaviour.

DESIGN: A case-control study.

SETTING: Spanish Association of Persistent COVID.

PARTICIPANT: Participants were 75 cases (64 women, 11 men, mean age 46.4 years ±8.9) and 42 controls (22 women, 20 men, mean age 53.5 years ±13.13).

INTERVENTION: An eye-tracking test based on visual search paradigm and the Adult Developmental Eye Movement Test were used to evaluate the participants.

MAIN MEASURES: The primary outcomes in the Adult Developmental Eye Movement Test were horizontal reading time, vertical reading time, and their ratio. And for the eye-tracking test the time to find the target, the duration, and the number of eye fixations.

RESULTS: In cases and controls, eye movement test results were horizontal(Hadj) reading time 74.2 ± 22.7 s vs 52.0 ± 6.1 s (p < .0001); vertical(Vadj) reading time 67.6 ± 17.8 s vs 50.4 ± 6.9 s (p < .0001); Hadj/Vadj ratio 0.9 ± 0.1 vs 1.0 ± 0 (p = .0032), respectively; and eye-tracking test results were fixation number 11.3 ± 3.07 vs 3.51 ± 2.57 (p < .0001); fixation duration 2.01 ± 0.79 s vs 1.5 ± 0.4 s (p = .0013), and time to find target 24.5 ± 8.0 vs 18 ± 9.4 (p = .0034), respectively.

CONCLUSIONS: Data showed a lower performance in oculomotor behaviour in people with long COVID-19, compared to healthy individuals. It cannot be affirmed an ocular musculature dysfunction; the differentiated behaviour could be associated to cognitive alterations affected in these people. Both tests used could be an useful tool for the clinical assessment of these participants. Further studies are needed to explore the utility of these procedures.}, } @article {pmid39094122, year = {2024}, author = {Günter, M and Mueller, KAL and Salazar, MJ and Gekeler, S and Prang, C and Harm, T and Gawaz, MP and Autenrieth, SE}, title = {Immune signature of patients with cardiovascular disease predicts increased risk for a severe course of COVID-19.}, journal = {European journal of immunology}, volume = {54}, number = {11}, pages = {e2451145}, doi = {10.1002/eji.202451145}, pmid = {39094122}, issn = {1521-4141}, support = {374031971-TRR 240//German Research Foundation (DFG)/ ; //Ministry of Science, Research and the Arts of the State of Baden-Württemberg: Long-COVID Funding/ ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *Cardiovascular Diseases/immunology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/immunology ; Aged ; *Killer Cells, Natural/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Adult ; Immunophenotyping ; Monocytes/immunology ; Natural Killer T-Cells/immunology ; Receptors, IgG/immunology ; Prospective Studies ; }, abstract = {Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. So far, however, there are hardly any strategies for predicting the course of SARS-CoV-2 infection in CVD patients at hospital admission. Thus, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 nonvaccinated participants, including uninfected and acutely SARS-CoV-2-infected CVD patients and healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4[+] T cells, and plasmablasts but fewer dendritic cells, CD16[+] monocytes, innate lymphoid cells, and CD8[+] T-cell subsets. Moreover, we identified an immune signature characterised by CD161[+] T cells, intermediate effector CD8[+] T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.}, } @article {pmid39093955, year = {2024}, author = {Clark, RA}, title = {Enough already: T cell inflammation and SARS-CoV-2 virus persist in Long Covid.}, journal = {Science immunology}, volume = {9}, number = {98}, pages = {eadr9661}, doi = {10.1126/sciimmunol.adr9661}, pmid = {39093955}, issn = {2470-9468}, mesh = {*COVID-19/immunology ; Humans ; *SARS-CoV-2/immunology ; *Inflammation/immunology ; *T-Lymphocytes/immunology ; }, abstract = {Virus and T cell inflammation persist in the tissues of patients with Long Covid.}, } @article {pmid39093104, year = {2024}, author = {Gustavson, AM and Rauzi, MR and Rasmussen, A and Raja, B and Kim, J and Davenport, TE}, title = {Leveraging and learning from the long COVID experience: Translating telerehabilitation into practice.}, journal = {Work (Reading, Mass.)}, volume = {79}, number = {3}, pages = {1567-1571}, pmid = {39093104}, issn = {1875-9270}, mesh = {Humans ; *COVID-19/epidemiology/rehabilitation ; *Telerehabilitation ; SARS-CoV-2 ; Pandemics ; Telemedicine/organization & administration ; }, abstract = {BACKGROUND: Telerehabilitation, or the delivery of rehabilitation services through telehealth platforms, has existed since the late 1990 s. Telerehabilitation was characterized by unprecedented, exponential growth at the beginning of the novel coronavirus-2019 (COVID-19) pandemic. Medical systems sought to reduce the likelihood of disease transmission by using telerehabilitation to limit physical proximity during routine care. This dramatic change in how medical care was delivered forced many professions to adapt processes and practices. Following the change, debates sparked regarding the best path to move forward for the betterment of patients, clinicians, systems, and society. Long COVID has emerged as a complex chronic health condition arising from COVID-19. The unique needs and dynamic disease process of Long COVID has incentivized medical systems to create equitable ways for patients to safely access interdisciplinary care.

OBJECTIVES: The purpose of this commentary is to describe what medical systems must consider when deploying high-quality telerehabilitation to deliver rehabilitation through asynchronous (e.g., text, portal) and synchronous modalities (e.g., phone or video). We highlight lessons learned to help guide decision-makers on key actions to support their patients and clinicians.

METHODS: Not applicable.

RESULTS: Not applicable.

CONCLUSIONS: Key action steps from our lessons learned may be used to address complex chronic health conditions such as Long COVID and prepare for future challenges that may disrupt medical systems.}, } @article {pmid39092750, year = {2024}, author = {Giannakopoulos, S and Park, J and Pak, J and Tallquist, MD and Verma, S}, title = {Post-COVID pulmonary injury in K18-hACE2 mice shows persistent neutrophils and neutrophil extracellular trap formation.}, journal = {Immunity, inflammation and disease}, volume = {12}, number = {8}, pages = {e1343}, pmid = {39092750}, issn = {2050-4527}, support = {U54MD007601//Ola HAWAII/ ; R21 AI140248/AI/NIAID NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; RS-2023-00266015//Ministry of Health & Welfare, Republic of Korea/ ; U54 GM138062/GM/NIGMS NIH HHS/United States ; //Hawaii Community Foundation/ ; R21AI140248/GF/NIH HHS/United States ; }, mesh = {Animals ; *Extracellular Traps/immunology ; *COVID-19/immunology/complications ; Mice ; *Neutrophils/immunology ; *SARS-CoV-2/immunology/physiology ; *Disease Models, Animal ; *Lung/pathology/immunology/virology ; Lung Injury/immunology/virology/pathology/etiology ; Angiotensin-Converting Enzyme 2/metabolism/genetics ; Neutrophil Infiltration/immunology ; Humans ; Pulmonary Fibrosis/immunology/pathology/etiology ; }, abstract = {The involvement of neutrophils in the lungs during the recovery phase of coronavirus disease 2019 (COVID-19) is not well defined mainly due to the limited accessibility of lung tissues from COVID-19 survivors. The lack of an appropriate small animal model has affected the development of effective therapeutic strategies. We here developed a long COVID mouse model to study changes in neutrophil phenotype and association with lung injury. Our data shows persistent neutrophil recruitment and neutrophil extracellular trap formation in the lungs for up to 30 days post-infection which correlates with lung fibrosis and inflammation.}, } @article {pmid39091579, year = {2024}, author = {Clark, P and Rosenberg, P and Oh, ES and Parker, A and Vannorsdall, T and Azola, A and Nickles, E and Galiatsatos, P and Malik, M}, title = {Methylphenidate for the Treatment of Post-COVID Cognitive Dysfunction (Brain Fog).}, journal = {Journal of medical cases}, volume = {15}, number = {8}, pages = {195-200}, pmid = {39091579}, issn = {1923-4163}, abstract = {A substantial number of patients develop cognitive dysfunction after contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significantly contributing to long-coronavirus disease (COVID) morbidity. Despite the urgent and overwhelming clinical need, there are currently no proven interventions to treat post-COVID cognitive dysfunction (PCCD). Psychostimulants like methylphenidate may enhance both noradrenergic and dopaminergic pathways in mesolimbic and pre-frontal areas, thus improving memory and cognition. We present a case series of six patients who were treated at the Johns Hopkins Post-Acute COVID-19 Team (PACT) clinic for PCCD with methylphenidate 5 - 20 mg in the context of routine clinical care and followed for 4 to 8 weeks. Baseline and post-treatment outcomes included subjective cognitive dysfunction and objective performance on a battery devised to measure cognitive dysfunction in long-COVID patients. Three out of the six patients reported subjective improvement with methylphenidate, one patient described it as "notable" and another as "marked" improvement in memory and concentration. We also found significant pre-treatment subjective complaints of cognitive dysfunction; however, formal cognitive assessment scores were not severely impaired. A statistically significant difference in pre and post scores, favoring intervention, was found for the following cognitive assessments: Hopkins verbal learning test (HVLT) immediate recall, HVLT delayed recall and category-cued verbal fluency. The current series demonstrates promising neurocognitive effects of methylphenidate for long-COVID cognitive impairment, particularly in recall and verbal fluency domains.}, } @article {pmid39090746, year = {2024}, author = {Barnekow, T and Peters, C and Dulon, M and Nienhaus, A}, title = {Impact of pre-existing conditions on the severity of post-COVID syndrome among workers in healthcare and social services in Germany.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {19}, number = {1}, pages = {32}, pmid = {39090746}, issn = {1745-6673}, abstract = {BACKGROUND: The underlying mechanisms of post-COVID syndrome (PCS) are still not fully understood. While pre-existing conditions have been described as a risk factor for severe PCS in the general population, data specific to different occupational groups in this context is lacking. This study aimed to investigate the impact of pre-existing conditions on severe post-COVID syndrome among the occupational group of healthcare and social services employees.

METHODS: Baseline data from a longitudinal, observational study were analysed. In February 2021, health workers who had a COVID-19 infection in 2020 were surveyed about sequelae of the infection. Factors influencing severe PCS with at least one persistent symptom categorised as severe were subjected to a multivariate logistic regression analysis.

RESULTS: Of a total of 2,053 participants, 21.5% had severe PCS. Underlying respiratory (OR 1.94; CI 1.44-2.61), cardiovascular (OR 1.35; CI 1.04-1.77) and urogenital (OR 1.79; CI 1.10-2.91) disease were risk factors for severe PCS overall. Respiratory and mental illnesses had a statistically significant impact on persistent fatigue/exhaustion, concentration/memory difficulties and shortness of breath categorised as severe. Urogenital disease was associated with severe fatigue/exhaustion. Other significant risk factors for severe PCS were female sex, smoking, physical exercise and hospitalisation due to COVID-19 infection.

CONCLUSION: Workers in healthcare and social services with pre-existing conditions may face a higher risk of developing severe PCS. Additional analyses performed as part of the longitudinal study will show if and how this result changes over time.}, } @article {pmid39090638, year = {2024}, author = {Tran, PT and Amill-Rosario, A and dosReis, S}, title = {Antidepressant treatment initiation among children and adolescents with acute versus long COVID: a large retrospective cohort study.}, journal = {Child and adolescent psychiatry and mental health}, volume = {18}, number = {1}, pages = {95}, pmid = {39090638}, issn = {1753-2000}, abstract = {BACKGROUND: Child and adolescent antidepressant use increased post-pandemic, but it is unknown if this disproportionally affected those who develop post-acute sequelae of coronavirus disease 2019 (COVID) or long COVID. This study compared the risk of antidepressant initiation among children and adolescents with long COVID with those who had COVID but did not have evidence of long COVID.

METHODS: Our retrospective cohort study of children and adolescents aged 3-17 years at the first evidence of COVID or long COVID from October 1, 2021 through April 4, 2022 was conducted within Komodo's Healthcare Map[™] database. The index date was the earliest date of a medical claim associated with a COVID (COVID comparators) or long COVID diagnosis (long COVID cases). The baseline period was six months before the index date. The outcome was antidepressant initiation within twelve months after the index date. Due to the large number of COVID relative to long COVID cases, COVID comparators were randomly selected with a ratio of 2 COVID to 1 long COVID. We used propensity score matching to control for confounding due to imbalances in the baseline covariates. Log-binomial models estimated the relative risk (RR) of antidepressant initiation in the propensity score matched sample. We conducted several sensitivity analyses to test the robustness of our findings to several assumptions.

RESULTS: Our child and adolescent sample included 18 274 with COVID and 9137 with long COVID. Compared with those with COVID, a larger proportion of long COVID children and adolescents had psychiatric disorders, psychotropic use, medical comorbidities, were previously hospitalized, or visited the emergency department. In the propensity score-adjusted analysis, the long COVID group had a statistically significant higher risk of antidepressant initiation relative to the COVID comparator (adjusted-RR: 1.40, 95% CI = 1.20, 1.62). Our findings were robust across sensitivity analyses.

CONCLUSIONS: The increased risk of antidepressant initiation following long COVID warrants further study to better understand the underlying reasons for this higher risk. Emerging evidence of long COVID's impact on child mental health has important implications for prevention and early interventions.}, } @article {pmid39090598, year = {2024}, author = {Su, Z and Li, Y and Xie, Y and Huang, Z and Cheng, A and Zhou, X and Li, J and Qin, R and Wei, X and Liu, Y and Xia, X and Song, Q and Zhao, L and Liu, Z and Xiao, D and Wang, C}, title = {Acute and long COVID-19 symptoms and associated factors in the omicron-dominant period: a nationwide survey via the online platform Wenjuanxing in China.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2086}, pmid = {39090598}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology ; Middle Aged ; Male ; Female ; China/epidemiology ; Adult ; Cross-Sectional Studies ; Aged ; Risk Factors ; *SARS-CoV-2 ; Surveys and Questionnaires ; Acute Disease ; }, abstract = {BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors.

METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models.

RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period.

CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.}, } @article {pmid39090366, year = {2024}, author = {Ignacio, M and Oesterle, S and Rodriguez-González, N and Lopez, G and Ayers, S and Carver, A and Wolfersteig, W and Williams, JH and Sabo, S and Parthasarathy, S}, title = {Limited Awareness of Long COVID Despite Common Experience of Symptoms Among African American/Black, Hispanic/Latino, and Indigenous Adults in Arizona.}, journal = {Journal of racial and ethnic health disparities}, volume = {}, number = {}, pages = {}, pmid = {39090366}, issn = {2196-8837}, support = {OT2 HL158287/HL/NHLBI NIH HHS/United States ; OT2HL158287/HL/NHLBI NIH HHS/United States ; }, abstract = {OBJECTIVES: Communities of color might disproportionately experience long-term consequences of COVID-19, known as Long COVID. We sought to understand the awareness of and experiences with Long COVID among African American/Black (AA/B), Hispanic/Latino (H/L), and Indigenous (Native) adults (18 + years of age) in Arizona who previously tested positive for COVID-19.

METHODS: Between December 2022 and April 2023, the Arizona Community Engagement Alliance (AZCEAL) conducted 12 focus groups and surveys with 65 AA/B, H/L and Native community members. Data from focus groups were analyzed using thematic analysis to identify emerging issues. Survey data provided demographic information about participants and quantitative assessments of Long COVID experiences were used to augment focus group data.

RESULTS: Study participants across all three racial/ethnic groups had limited to no awareness of the term Long COVID, yet many described experiencing or witnessing friends and family endure physical symptoms consistent with Long COVID (e.g., brain fog, loss of memory, fatigue) as well as associated mental health issues (e.g., anxiety, worry, post-traumatic stress disorder). Participants identified a need for Long COVID mental health and other health resources, as well as increased access to Long COVID information.

CONCLUSION: To prevent Long COVID health inequities among AA/B, H/L, and Native adults living in AZ, health-related organizations and providers should increase access to culturally relevant, community-based Long COVID-specific information, mental health services, and other health resources aimed at serving these populations.}, } @article {pmid39089276, year = {2024}, author = {Gonevski, M}, title = {RATIONALE AND ANALYSIS OF THE EFFECT OF HBOT THERAPY IN THE RECOVERY OF LONG COVID PATIENTS.}, journal = {Georgian medical news}, volume = {}, number = {350}, pages = {82-87}, pmid = {39089276}, issn = {1512-0112}, mesh = {Humans ; *COVID-19/therapy/complications ; Male ; Middle Aged ; *Hyperbaric Oxygenation/methods ; Female ; Adult ; Aged ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fatigue/therapy ; Young Adult ; Treatment Outcome ; Dyspnea/therapy/virology ; }, abstract = {Long COVID is a common occurrence after an infection with COVID-19. Most frequent symptoms are fatigue, shortness of breath, and cognitive dysfunction. Options for treatment are limited, mainly symptomatic. There is a solid theoretical background for the successful treatment with Hyperbaric Oxygen Therapy (HBOT) of the pathophysiological changes caused by the COVID-19 infection and their reversal. Case presentation: The data presented was collected from the test results of total of 63 male and female patients, treated from 15th January 2021 to 19th April 2022, aged 22 to 74 years old, all of them presenting with symptoms of Long COVID. A standard 2.4 ATA HBOT treatment table for approved elective HBOT indications was used for the treatment of Long COVID patients, with a course duration of 10 or 15 sessions. The key concept is that HBOT works on a cellular level, specifically affecting the oxidative phosphorylation and energy metabolism in the mitochondria. Results: Hyperbaric Oxygen Therapy delivered positive results in all observed Long COVID related symptoms, particularly those associated with the nervous system, cognitive function, psychological well-being, and physical fatigue. Approximately 90% of all patients improved compared to their initial state, in most cases significantly. No adverse effects were reported. Feedback received three months after treatment demonstrated that the benefits were persistent.}, } @article {pmid39087973, year = {2024}, author = {Ren, Y and Zhang, Z and Li, HP and Zhang, PJ and Duo, J and Kong, H}, title = {A Comprehensive Overview of the Stellate Ganglion Block Throughout the Past Three Decades: A Bibliometric Analysis.}, journal = {Pain physician}, volume = {27}, number = {5}, pages = {E597-E610}, pmid = {39087973}, issn = {2150-1149}, mesh = {*Bibliometrics ; *Stellate Ganglion ; Humans ; *Autonomic Nerve Block/methods ; }, abstract = {BACKGROUND: Over the past 3 decades, clinicians and scholars have used and studied the stellate ganglion block (SGB) extensively, making this field a highly anticipated research hot spot. To the best of our knowledge, there has been no bibliometric analysis of the SGB until now.

OBJECTIVE: Our study aimed to complete multiple tasks regarding SGB research: identify the collaboration and impact of countries, institutions, journals, and authors, evaluate the knowledge base, trace the trends in hot spots, and explore the emerging topics relevant to the field.

STUDY DESIGN: A bibliometric analysis.

METHODS: Publications that were associated with the SGB and published between the years of 1993 and 2022 were retrieved from the Web of Science Core Collection on September 21st, 2023. CiteSpace 6.1.R6 and VOSviewer 1.6.18 were used to perform bibliometric and knowledge-map analyses.

RESULTS: This study found a total of 837 publications originating from 51 countries and 1006 institutions. These articles were published in 393 journals. The United States was the country that produced the most articles focused on SGB, and the University of California, Los Angeles was the institution associated with the greatest number of publications. The anesthesiology and cardiology journals surveyed for this study published the most articles and received the most citations. Among the authors whose works were examined, Kitajima T had the greatest number of published articles, and Lipov E was the most frequently cited co-author. Five main domains of SGB research included electrical storm and refractory ventricular arrhythmia, breast cancer and climacteric medicine, post-traumatic stress disorder, pain management, and cerebrovascular diseases. The latest hot topics involving this field focused on SGB's anti-arrhythmic and anti-cerebral vasospasm effects and its treatment of long COVID syndrome.

LIMITATIONS: Data were retrieved only from the WoSCC; therefore, publications in other databases might have been missed.

CONCLUSION: This comprehensive bibliometric analysis conducted a complete overview of SGB research, which was helpful in furthering our understanding of research trends and locating research hot spots and gaps in this domain. This field is developing rapidly and will garner significant and continuous attention from future scholars.}, } @article {pmid39087731, year = {2024}, author = {Kehl-Floberg, K and Pop-Vicas, A and Giles, G and Edwards, D}, title = {The Functional Consequences of Long COVID Need to Be Addressed by Occupational Therapists.}, journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}, volume = {78}, number = {5}, pages = {}, doi = {10.5014/ajot.2024.050707}, pmid = {39087731}, issn = {0272-9490}, mesh = {Humans ; *COVID-19 ; *Occupational Therapy ; *Post-Acute COVID-19 Syndrome ; *Activities of Daily Living ; SARS-CoV-2 ; Quality of Life ; Occupational Therapists ; }, abstract = {Long COVID-persistent health complications after recovery from coronavirus disease 2019 infection-is associated with activity limitations in nearly 48 million U.S. adults, affecting work, leisure, family, and community functioning. Occupational therapists are experts in customizing interventions to maximize performance of daily routines, and often treat individuals who experience similar functional impacts to those observed in long COVID. The large number of people experiencing new disability, as well as a lack of medical treatment options, make occupational therapy a crucial component of long-COVID research and multidisciplinary management. In this column, we discuss actionable steps occupational therapists can take to place them at the forefront of maximizing functional and quality-of-life outcomes for people with long COVID.}, } @article {pmid39086937, year = {2024}, author = {Lofrano-Porto, A and D'Isabel, S and Smith, DL}, title = {Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1387499}, pmid = {39086937}, issn = {2296-858X}, abstract = {In the wake of the COVID-19 pandemic, millions worldwide are still struggling with persistent or recurring symptoms known as long COVID. Fatigue is one of the most prevalent symptoms associated with long COVID, and for many it can be debilitating. Understanding the potential pathological processes that link fatigue to long COVID is critical to better guide treatment. Challenges with diagnosis and treatment are reviewed, recognizing that post-COVID fatigue does not always present with corroborating clinical evidence, a situation that is frustrating for both patients and healthcare providers. Firefighters are a group of public safety workers who are particularly impacted by long COVID-related fatigue. Firefighters must be able to engage in strenuous physical activity and deal with demanding psychological situations, both of which may be difficult for those suffering from fatigue. Disruption in public safety worker health can potentially impact community welfare. This review creates a framework to explain the clinical-pathological features of fatigue resulting from long COVID, addresses diagnosis and treatment challenges, and explores the unique impact fatigue may pose for public safety workers and their organizations.}, } @article {pmid39085687, year = {2024}, author = {Za, P and Papalia, GF and Gregori, P and Vasta, S and Papalia, R}, title = {Osteonecrosis as a manifestation of Long-COVID Syndrome: a systematic review.}, journal = {Musculoskeletal surgery}, volume = {}, number = {}, pages = {}, pmid = {39085687}, issn = {2035-5114}, abstract = {Purpose SARS-CoV-2 is an RNA virus responsible for COVID-19 pandemic. Some authors described the set of persistent symptoms COVID-related as "Long-COVID Syndrome." Several cases of post-COVID-19 osteonecrosis (ON) are described. Our primary aim was to study the hypothetical correlation between SARS-CoV-2 infection and ON; our secondary aim was to understand if ON can be considered part of Long-COVID. Materials and methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines. Because COVID-19 is a recently described disease, we included all levels of evidence studies. We excluded studies lacking specification regarding the use of corticosteroids (CCS) and studies not related to COVID-19. The variables extracted were age, sex, risk factors, affected joints, signs and symptoms, magnetic resonance imaging (MRI) and X-ray features, histology, treatment of COVID-19, dose and duration of treatment with CCS, treatment of ON, follow-up, and treatment outcome. Results A total of 13 studies were included, involving 95 patients and 159 joints. Time between the diagnosis of COVID-19 and the onset of symptoms related to ON was 16 weeks on average. Time between the onset of symptoms and the MRI was 6 weeks. An average of 926.4 mg of prednisolone equivalent per patient were administered. On average, CCS were administered for 20.6 days. Conclusions Patients with a history of COVID-19 infection developed osteonecrosis prematurely and with a lower dose of CCS than usually reported in the literature. Symptoms of osteonecrosis occur within the interval of the period described as Long-COVID. Surgeons should not underestimate the persistence of arthralgia when a history of SARS-CoV-2 infection and use of CCS is reported.}, } @article {pmid39085662, year = {2024}, author = {Fioravanti, A and Antonelli, M and Vitale, M}, title = {Advances in modern Balneology: new evidence-based indications from recent studies.}, journal = {International journal of biometeorology}, volume = {68}, number = {11}, pages = {2447-2452}, pmid = {39085662}, issn = {1432-1254}, mesh = {Humans ; *Balneology/methods/trends ; }, abstract = {Balneotherapy (BT) is a therapeutic approach that utilizes various forms of water-based treatments to promote health and well-being. BT possesses a rich historical heritage and has garnered recognition from esteemed institutions such as the World Health Organization (WHO). Recent scientific research enables the identification of relevant diseases (obesity, metabolic diseases, sleep disorders, mental health conditions, Long-COVID-19, and cancer rehabilitation) that could potentially benefit from balneo-therapeutic treatments, thereby presenting new avenues of opportunity for SPA ("Salus per Aquam") medicine. These conditions exemplify the potential benefits of BT for ailments beyond the traditional scope of treatment associated with BT (most commonly osteoarthritis, fibromyalgia, rheumatic back pain, and chronic inflammatory respiratory or skin disorders). Overall, the current scientific evidence suggests that BT holds significant potential for enhancing both individual wellbeing and public health. However, further high-quality clinical trials are essential to corroborate these preliminary findings and to provide critical insights into the therapeutic benefits of BT, paving the way for its broader integration into healthcare practices and public health initiatives.}, } @article {pmid39084516, year = {2024}, author = {Li, B and Bai, J and Xiong, Y and Guo, D and Fu, B and Deng, G and Wu, H}, title = {Understanding the mechanisms and treatments of long COVID to address future public health risks.}, journal = {Life sciences}, volume = {353}, number = {}, pages = {122938}, doi = {10.1016/j.lfs.2024.122938}, pmid = {39084516}, issn = {1879-0631}, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; *Public Health ; }, abstract = {The 2019 coronavirus disease (COVID-19), triggered by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has seen numerous individuals undergo and recover from it, drawing extensive attention to their health conditions. Extensive studies indicate that even after surpassing the acute phase of infection, patients continue to experience persistent symptoms such as fatigue, pain, depression, weakening, and anosmia. COVID-19 appears not to have concluded but rather to persist long-term in certain individuals, termed as "long COVID." This represents a heterogeneous ailment involving multiple organ systems, with a perceived complex and still elusive pathogenesis. Among patients with long COVID, observations reveal immune dysregulation, coagulation impairments, and microbial dysbiosis, considered potential mechanisms explaining sustained adverse outcomes post COVID-19. Based on the multifactorial nature, varied symptoms, and heterogeneity of long COVID, we have summarized several categories of current therapeutic approaches. Furthermore, the symptoms of long COVID resemble those of other viral illnesses, suggesting that existing knowledge may offer novel insights into long-term COVID implications. Here, we provide an overview of existing literature associated with long COVID and summarize potential mechanisms, treatment modalities, and other analogous conditions. Lastly, we underscore the inadequacies in long COVID treatment approaches and emphasize the significance of conducting further research and clinical trials.}, } @article {pmid39083764, year = {2024}, author = {Ely, EW and Brown, LM and Fineberg, HV and , }, title = {Long Covid Defined.}, journal = {The New England journal of medicine}, volume = {391}, number = {18}, pages = {1746-1753}, pmid = {39083764}, issn = {1533-4406}, } @article {pmid39083202, year = {2024}, author = {Huang, Y and Wang, W and Liu, Y and Wang, Z and Cao, B}, title = {COVID-19 vaccine updates for people under different conditions.}, journal = {Science China. Life sciences}, volume = {67}, number = {11}, pages = {2323-2343}, pmid = {39083202}, issn = {1869-1889}, mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *COVID-19/prevention & control/immunology/epidemiology ; *SARS-CoV-2/immunology ; Vaccine Efficacy ; Immunocompromised Host/immunology ; }, abstract = {SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.}, } @article {pmid39081653, year = {2024}, author = {Dębski, M and Tsampasian, V and Vassiliou, VS}, title = {Post-COVID Condition in Patients With Cardiovascular Disease: Are Antivirals the Answer?.}, journal = {JACC. Advances}, volume = {3}, number = {6}, pages = {100962}, pmid = {39081653}, issn = {2772-963X}, } @article {pmid39081650, year = {2024}, author = {Patel, R and Dani, SS and Khadke, S and Kumar, A and Ahmad, J and Saji, AM and Shah, J and Mehta, N and Wener, K and McQuillen, DP and Abraham, G and Faust, J and Maley, J and Patel, S and Mullington, J and Wachter, RM and Mosenthal, A and Sax, PE and Ganatra, S}, title = {Nirmatrelvir-Ritonavir for Acute COVID-19 in Patients With Cardiovascular Disease and Postacute Sequelae of SARS-CoV-2 Infection.}, journal = {JACC. Advances}, volume = {3}, number = {6}, pages = {100961}, pmid = {39081650}, issn = {2772-963X}, abstract = {BACKGROUND: There is limited evidence of association of nirmatrelvir-ritonavir (NMV-r) and incidence of postacute sequelae of SARS-CoV-2 infection (PASC) in patients with pre-existing cardiovascular disease (CVD).

OBJECTIVES: The objective of this study was to assess the association of NMV-r in nonhospitalized, vaccinated patients with pre-existing CVD and occurrence of PASC.

METHODS: We conducted a retrospective cohort study utilizing the TriNetX research network, including vaccinated patients with pre-existing CVD who developed COVID-19 between December 2021 and December 2022. Two cohorts were created based on NMV-r administration within 5 days of diagnosis: NMV-r and non-NMV-r cohort. The main outcome was presence of PASC, assessed between 30 to 90 days and 90 to 180 days after index COVID-19 infection. After propensity score matching, both cohorts were compared using t-test and chi-square test for continuous and categorical variables, respectively.

RESULTS: A total of 26,953 patients remained in each cohort after propensity score matching. Broadly defined PASC occurred in 6,925 patients (26%) in the NMV-r cohort vs 8,150 patients (30.6%) in the non-NMV-r cohort (OR: 0.80; 95% CI: 0.76-0.82; P < 0.001) from 30 to 90 days and in 6,692 patients (25.1%) as compared to 8,910 patients (33.5%) (OR: 0.25, 95% CI: 0.23-0.29; P < 0.001) from 90 to 180 days. Similarly, narrowly defined PASC occurred in 5,335 patients (20%) in the NMV-r cohort vs 6,271 patients (23.6%) in the non-NMV-r cohort between 30 and 90 days (OR: 0.81, 95% CI: 0.78-0.84, P < 0.001) and in 5,121 patients (19.2%) as compared to 6,964 patients (26.1%) (OR: 0.67, 95% CI: 0.64-0.70, P < 0.001) between 90 and 180 days.

CONCLUSIONS: NMV-r in nonhospitalized vaccinated patients with pre-existing CVD with COVID-19 was associated with a reduction in PASC and health care utilization.}, } @article {pmid39081420, year = {2024}, author = {Gollapudi, S and Chimurkar, V}, title = {Comprehensive Insights Into the Multi-faceted Manifestations of COVID-19: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e63493}, pmid = {39081420}, issn = {2168-8184}, abstract = {The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the ensuing COVID-19 pandemic had far-reaching and multifaceted effects on global health. This paper provides a comprehensive overview of the physical, extrapulmonary, and psychological manifestations associated with COVID-19. It highlights the wide-ranging impact of the virus on various organ systems, including the respiratory, cardiovascular, renal, gastrointestinal, ocular, dermatologic, and nervous systems. Additionally, it explores the complex connections between COVID-19 infection and neuropsychiatric symptoms, shedding light on the potential underlying mechanisms. The paper also delves into the phenomenon of "long COVID," a condition characterized by persistent symptoms extending well beyond the disease's acute phase. It discusses the diverse and often debilitating symptoms that individuals with long COVID may experience, encompassing physical, cognitive, and psychological aspects. The complexity and variability of long COVID underscore the challenges it poses to healthcare professionals and the importance of ongoing research to understand its underlying mechanisms. Furthermore, the paper touches on the current state of knowledge regarding the aetiology of long COVID and the various approaches to symptom management and treatment. While a definitive cure remains elusive, efforts are underway to alleviate the burden of long COVID through pharmacological interventions, physical therapy, cognitive-behavioral therapy, and support networks. This paper comprehensively explores COVID-19's far-reaching effects, emphasizing the need for a holistic and interdisciplinary approach to understanding and managing the diverse manifestations of this global health challenge. Ongoing research and collaborative efforts are essential in addressing the complex and evolving nature of COVID-19 and its aftermath.}, } @article {pmid39081289, year = {2024}, author = {Ghosh, P and Niesen, MJM and Pawlowski, C and Bandi, H and Yoo, U and Lenehan, PJ and Kumar-M, P and Nadig, M and Ross, J and Ardhanari, S and O'Horo, JC and Venkatakrishnan, AJ and Rosen, CJ and Telenti, A and Hurt, RT and Soundararajan, V}, title = {Case-control study on post-COVID-19 conditions reveals severe acute infection and chronic pulmonary disease as potential risk factors.}, journal = {iScience}, volume = {27}, number = {8}, pages = {110406}, pmid = {39081289}, issn = {2589-0042}, abstract = {Post-COVID-19 conditions (long COVID) has impacted many individuals, yet risk factors for this condition are poorly understood. This retrospective analysis of 88,943 COVID-19 patients at a multi-state US health system compares phenotypes, laboratory tests, medication orders, and outcomes for 1,086 long-COVID patients and their matched controls. We found that history of chronic pulmonary disease (CPD) (odds ratio: 1.9, 95% CI: [1.5, 2.6]), migraine (OR: 2.2, [1.6, 3.1]), and fibromyalgia (OR: 2.3, [1.3, 3.8]) were more common for long-COVID patients. During the acute infection phase long COVID patients exhibited high triglycerides, low HDL cholesterol, and a high neutrophil-lymphocyte ratio; and were more likely hospitalized (5% vs. 1%). Our findings suggest severity of acute infection and history of CPD, migraine, chronic fatigue syndrome (CFS), or fibromyalgia as risk factors for long COVID. These results suggest that suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.}, } @article {pmid39081145, year = {2024}, author = {Galúcio, VCA and de Menezes, DC and Chaves, ECR and van den Berg, AVS and de Lima, PDL and da Costa Vasconcelos, PF and Quaresma, JAS and Falcão, LFM}, title = {Laboratory profiling of patients with long COVID in the Brazilian Amazon region: A cross-sectional study.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29828}, doi = {10.1002/jmv.29828}, pmid = {39081145}, issn = {1096-9071}, support = {006/2020//Amazon Foundation for Research Support (FAPESPA)/ ; 09/2021//Secretary of Science, Technology, and Higher, Professional and Technological Education (SECTET)/ ; 13/2020//Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES)/ ; 406360/2022-7//National Council for Scientific and Technological Development-Brazil (CNPq)/ ; }, mesh = {Humans ; *COVID-19/blood/epidemiology/diagnosis ; Brazil/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Aged ; Adult ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; C-Reactive Protein/analysis ; Aged, 80 and over ; }, abstract = {The condition commonly referred to as long coronavirus disease (COVID) is characterized by the continuation of symptoms, sometimes accompanied by new symptoms that persist after the resolution of acute coronavirus disease 2019 (COVID-19). This observational cross-sectional study investigated 332 patients with long COVID in the Brazilian Amazon region. The study aimed to elucidate the systemic interactions associated with long COVID by compiling the findings related to hematological, coagulation, immunological, metabolic, hepatic, renal, and muscular profiles. Participants with long COVID were identified using rigorous criteria and underwent thorough laboratory examinations. The obtained data were subsequently analyzed, allowing for comparisons, associations, and correlations between findings within distinct groups in the study. Significant associations were observed between hospitalization during the acute phase and persistent laboratory abnormalities, suggesting a potential link between acute severity and long-term effects. Notably, individuals with long COVID for over a year exhibited elevated levels of monocytes, prolonged prothrombin times, reduced prothrombin activity, high levels of lactate dehydrogenase, and an increased frequency of qualitative C-reactive protein detection. This study provides valuable insights into the laboratory risk profile of patients with long COVID, particularly in the unique context of the Amazon region, where patients exhibit persistent symptoms lasting up to 1261 days.}, } @article {pmid39080694, year = {2024}, author = {Newlands, F and Fox-Smith, L and Balakrishnan, S and Lord, G and Chalder, T and Dalrymple, E and Ford, T and Harnden, A and Heyman, I and Ladhani, SN and Pereira, SMP and Segal, TY and Stephenson, T and Whittaker, E and Shafran, R}, title = {Using a novel methodology to map Post-COVID services for children and young people in England: a web-based systematic search.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {863}, pmid = {39080694}, issn = {1472-6963}, support = {Award number: 183885//Beryl Alexander Charity/ ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Humans ; Child Health Services/organization & administration ; *COVID-19/epidemiology/therapy ; England/epidemiology ; Health Services Accessibility ; *Internet ; }, abstract = {BACKGROUND: Post-COVID Condition (PCC), also known as 'Long COVID,' refers to persistent symptoms following a coronavirus 2 (SARS-CoV-2) infection. The prevalence of PCC in children and adolescents varies, impacting multiple body systems and affecting daily functioning. Specialised paediatric hubs were established in England to address the needs of young individuals with PCC. Additional local services also emerged, yet patients report challenges accessing services. To better understand the landscape of paediatric PCC services, we used a novel methodology using a web-based systematic search.

METHODS: A web-based search was conducted in July 2023 using DEVONagent Pro. Search terms related to Long COVID and Pediatrics in England. Eligible sources providing information on PCC services for children and young people were included. A supplementary manual search and NHS England Post-COVID Network were also consulted. Data extraction included service location, characteristics, and referral pathways. Population estimates were derived from UK Census data.

RESULTS: Among 342 identified records, 27 services met eligibility criteria, distributed unevenly across regions. Specialised hubs covered 13 locations, while additional services were concentrated in the South of England and London. Services varied in team composition, age range treated, and support offered. A lack of standardised approaches for paediatric PCC was evident.

DISCUSSION: We used a novel methodology for systematically mapping online resources, providing valuable insights into service accessibility and aiding the identification of potential gaps. We observed geographical disparities in access to paediatric PCC services and the absence of standardised approaches in managing symptoms. Given the challenges faced by young individuals seeking support for their PCC the need for equitable and standardised care became apparent. The study contributes to closing the research-practice gap and calls for further research to identify effective treatments for paediatric PCC, acknowledging the diversity of reported symptoms and the importance of tailored approaches.}, } @article {pmid39079687, year = {2024}, author = {Jung, F and Zülke, A and Wirkner, K and Reusche, M and Engel, C and Sander, C and Witte, V and Zeynalova, S and Loeffler, M and Villringer, A and Saur, D and Schomerus, G and Luppa, M and Riedel-Heller, SG}, title = {[Health Literacy, Contact Points, Unmet Subjective Needs and Treatment Satisfaction of those Affected by Long Covid with Long-Lasting Neuropsychiatric Symptoms].}, journal = {Psychiatrische Praxis}, volume = {51}, number = {8}, pages = {418-425}, doi = {10.1055/a-2334-1822}, pmid = {39079687}, issn = {1439-0876}, mesh = {Humans ; *Health Literacy ; *COVID-19/psychology ; Female ; Male ; Middle Aged ; *Patient Satisfaction/statistics & numerical data ; Germany ; Aged ; Adult ; *Mental Disorders/therapy/psychology ; Health Services Needs and Demand/statistics & numerical data ; SARS-CoV-2 ; Chronic Disease ; Needs Assessment ; }, abstract = {OBJECTIVE: The bejective was to determine health literacy (HL) and care aspects of those affected by Long-COVID.

METHOD: 407 patients with Long-COVID and long-term neuropsychiatric symptoms were interviewed in the LIFE study center. In addition to descriptive analyses, regression models were calculated to examine the relationships between health literacy (HLS-EU-Q16) and various aspects of care (RehaQ-N1).

RESULTS: The results show that 35.8% had problematic and 17.9% had inadequate HL. The majority of subjective needs were unmet and 47.7% of those affected were dissatisfied with the therapy they received.

DISCUSSION: Among those affected by Long-COVID, subjective HL is rather reduced. The healthcare system appears to be unprepared for these patients, which is reflected in unmet needs and low treatment satisfaction. This was even more pronounced among those exhibiting lower HL.}, } @article {pmid39079463, year = {2024}, author = {Walker, J}, title = {Medical narrative: Finding my new "Normal" with Sjogren's Syndrome.}, journal = {Journal of medical imaging and radiation sciences}, volume = {55}, number = {3}, pages = {101731}, doi = {10.1016/j.jmir.2024.101731}, pmid = {39079463}, issn = {1876-7982}, mesh = {Female ; Humans ; *Sjogren's Syndrome ; }, } @article {pmid39079061, year = {2024}, author = {Schröeder, N and Feter, N and Caputo, EL and Delpino, FM and da Silva, LS and Rocha, JQS and Paz, IA and da Silva, CN and da Cunha, LL and Vieira, YP and Reichert, FF and Silva, MC and Rombaldi, AJ}, title = {Association between food insecurity and long COVID in adults from southern Brazil: findings of the PAMPA cohort.}, journal = {Journal of public health (Oxford, England)}, volume = {46}, number = {4}, pages = {e623-e631}, doi = {10.1093/pubmed/fdae134}, pmid = {39079061}, issn = {1741-3850}, support = {21/2551-0002071-7//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; 405496/2021-4//National Council for Scientific and Technological Development/ ; }, mesh = {Humans ; Brazil/epidemiology ; Female ; Male ; *Food Insecurity ; Adult ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Surveys and Questionnaires ; Socioeconomic Factors ; }, abstract = {BACKGROUND: Social and economic factors, such as food insecurity, contribute to long coronavirus disease (COVID). During the pandemic, a significant rise in food insecurity was observed, both in Brazil and worldwide. We aimed to investigate the association between food insecurity and long COVID in Brazilian adults.

METHODS: Cross-sectional study nested within the Prospective study About Mental and Physical Health in Adults (PAMPA) Cohort. Participants completed an online questionnaire in June 2022. We assessed food insecurity using the Brazilian Scale of Food Insecurity. Long COVID was defined as any post-coronavirus disease 2019 symptoms that persisted for at least 3 months after infection.

RESULTS: A total of 956 participants were included (74.0% female, median age 36 (Interquartile Range [IQR] (29-45.7). The prevalence of food insecurity was 29.4%, and 77.8% had long COVID. Food insecurity was associated with an increased probability of long COVID (prevalence ratio [PR]: 1.15, 95% confidence interval [CI]: 1.08-1.22). Participants in food insecurity situations had a higher likelihood of experiencing neurological (PR: 1.19, 95% CI: 1.10-1.28), pulmonary (PR: 1.33, 95% CI: 1.17-1.52) and gastrointestinal (PR: 1.57, 95% CI: 1.31-1.88) symptoms after infection.

CONCLUSIONS: Food insecurity was associated with long COVID. Governments must plan public policies to mitigate the effects of long COVID and food insecurity.}, } @article {pmid39078547, year = {2024}, author = {Schwartz, CE and Borowiec, K and Rapkin, BD}, title = {The faces of Long-COVID: interplay of symptom burden with socioeconomic, behavioral and healthcare factors.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {10}, pages = {2855-2867}, pmid = {39078547}, issn = {1573-2649}, mesh = {Humans ; Female ; *COVID-19/psychology/epidemiology ; Male ; Middle Aged ; *Quality of Life/psychology ; *SARS-CoV-2 ; *Socioeconomic Factors ; Adult ; Cost of Illness ; Aged ; Post-Acute COVID-19 Syndrome ; Adaptation, Psychological ; Comorbidity ; Stress, Psychological ; Symptom Burden ; }, abstract = {AIMS: The long-term effects of COVID-19 (Long COVID) include 19 symptoms ranging from mild to debilitating. We examined multidimensional correlates of Long COVID symptom burden.

METHODS: This study focused on participants who reported having had COVID in Spring 2023 (n = 656; 85% female, mean age = 55, 59% college). Participants were categorized into symptom-burden groups using Latent Profile Analysis of 19 Long-COVID symptoms. Measures included demographics; quality of life and well-being (QOL); and COVID-specific stressors. Bivariate and multivariate associations of symptom burden were examined.

RESULTS: A three-profile solution reflected low, medium, and high symptom burden, aligning with diagnosis confirmation and treatment by a healthcare provider. Higher symptom burden was associated with reporting more comorbidities; being unmarried, difficulty paying bills, being disabled from work, not having a college degree, younger age, higher body mass index, having had COVID multiple times, worse reported QOL, greater reported financial hardship and worry; maladaptive coping, and worse healthcare disruption, health/healthcare stress, racial-inequity stress, family-relationship problems, and social support. Multivariate modeling revealed that financial hardship, worry, risk-taking, comorbidities, health/healthcare stress, and younger age were risk factors for higher symptom burden, whereas social support and reducing substance use were protective factors.

CONCLUSIONS: Long-COVID symptom burden is associated with substantial, modifiable social and behavioral factors. Most notably, financial hardship was associated with more than three times the risk of high versus low Long-COVID symptom burden. These findings suggest the need for multi-pronged support in the absence of a cure, such as symptom palliation, telehealth, social services, and psychosocial support.}, } @article {pmid39076533, year = {2024}, author = {Redel, AL and Miry, F and Hellemons, ME and Oswald, LMA and Braunstahl, GJ}, title = {Effect of lactoferrin treatment on symptoms and physical performance in long COVID patients: a randomised, double-blind, placebo-controlled trial.}, journal = {ERJ open research}, volume = {10}, number = {4}, pages = {}, pmid = {39076533}, issn = {2312-0541}, abstract = {BACKGROUND: Long COVID is a heterogeneous condition with a variety of symptoms that persist at least 3 months after SARS-CoV-2 infection, often with a profound impact on quality of life. Lactoferrin is an iron-binding glycoprotein with anti-inflammatory and antiviral properties. Current hypotheses regarding long COVID aetiology include ongoing immune activation, viral persistence and auto-immune dysregulation. Therefore, we hypothesised that long COVID patients may potentially benefit from lactoferrin treatment. The aims of the present study were to investigate the effect of lactoferrin on various long COVID domains: fatigue, anxiety, depression, cognitive failure and muscle strength.

METHODS: We performed a randomised, double-blind, placebo-controlled trial in long COVID patients aged 18-70 years within 12 months after proven SARS-CoV-2 infection. Patients were randomised (1:1) to 6 weeks of lactoferrin (1200 mg daily) or placebo. At three hospital visits (T0, T6 and T12 weeks), patient-reported outcome measures were collected, physical performance tests were performed and blood was drawn. The difference in fatigue at T6 was the primary outcome.

RESULTS: 72 participants were randomised to lactoferrin (n=36) or placebo (n=36). We found a significant decrease in fatigue, as measured with the Fatigue Assessment Scale, between T0 and T6 in both study arms, but without significant difference between the study arms (lactoferrin: 3.9, 95% CI 2.3-5.5, p=0.007; placebo: 4.1, 95% CI 2.3-5.9, p=0.013). No significant differences were found in any of the other outcomes in favour of the lactoferrin arm at T6 or T12.

CONCLUSION: Although both long COVID arms showed improved clinical outcomes at T6, the improvement did not continue until T12. Lactoferrin provided no benefit in terms of fatigue, other patient-reported outcome measures or physical functioning.}, } @article {pmid39074096, year = {2024}, author = {Venkatesh, AK and Yu, H and Malicki, C and Gottlieb, M and Elmore, JG and Hill, MJ and Idris, AH and Montoy, JCC and O'Laughlin, KN and Rising, KL and Stephens, KA and Spatz, ES and Weinstein, RA and , }, title = {The association between prolonged SARS-CoV-2 symptoms and work outcomes.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0300947}, pmid = {39074096}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Adult ; Middle Aged ; *SARS-CoV-2/isolation & purification ; Prospective Studies ; Return to Work/statistics & numerical data ; United States/epidemiology ; Employment ; Self Report ; Pandemics ; Absenteeism ; Young Adult ; }, abstract = {While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed a baseline and three-month electronic survey. At three months post-infection, 40.8% of participants reported at least one SARS-CoV-2 symptom and 9.6% of participants reported five or more SARS-CoV-2 symptoms. When asked about missed work due to their SARS-CoV-2 infection at three months, 7.2% of participants reported missing ≥10 workdays and 13.9% of participants reported not returning to work since their infection. At three months, participants with ≥5 symptoms had a higher adjusted odds ratio of missing ≥10 workdays (2.96, 95% CI 1.81-4.83) and not returning to work (2.44, 95% CI 1.58-3.76) compared to those with no symptoms. Prolonged SARS-CoV-2 symptoms were common, affecting 4-in-10 participants at three-months post-infection, and were associated with increased odds of work loss, most pronounced among adults with ≥5 symptoms at three months. Despite the end of the federal Public Health Emergency for COVID-19 and efforts to "return to normal", policymakers must consider the clinical and economic implications of the COVID-19 pandemic on people's employment status and work absenteeism, particularly as data characterizing the numerous health and well-being impacts of Long COVID continue to emerge. Improved understanding of risk factors for lost work time may guide efforts to support people in returning to work.}, } @article {pmid39073834, year = {2024}, author = {Scheperjans, F and Levo, R and Bosch, B and Lääperi, M and Pereira, PAB and Smolander, OP and Aho, VTE and Vetkas, N and Toivio, L and Kainulainen, V and Fedorova, TD and Lahtinen, P and Ortiz, R and Kaasinen, V and Satokari, R and Arkkila, P}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {925-938}, pmid = {39073834}, issn = {2168-6157}, mesh = {Humans ; *Parkinson Disease/therapy ; Middle Aged ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Aged ; Double-Blind Method ; Adult ; Treatment Outcome ; Dysbiosis/therapy ; }, abstract = {IMPORTANCE: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.

OBJECTIVE: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.

This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.

INTERVENTION: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.

MAIN OUTCOMES AND MEASURES: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).

RESULTS: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.

CONCLUSIONS AND RELEVANCE: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04854291.}, } @article {pmid39073768, year = {2024}, author = {Ćorović, A and Zhao, X and Huang, Y and Newland, SR and Gopalan, D and Harrison, J and Giakomidi, D and Chen, S and Yarkoni, NS and Wall, C and Peverelli, M and Sriranjan, R and Gallo, A and Graves, MJ and Sage, A and Lyons, PA and Sithole, N and Bennett, MR and Rudd, JHF and Mallat, Z and Zhao, TX and Nus, M and Tarkin, JM}, title = {Coronavirus disease 2019-related myocardial injury is associated with immune dysregulation in symptomatic patients with cardiac magnetic resonance imaging abnormalities.}, journal = {Cardiovascular research}, volume = {120}, number = {14}, pages = {1752-1767}, pmid = {39073768}, issn = {1755-3245}, support = {/WT_/Wellcome Trust/United Kingdom ; //Cambridge British Heart Foundation/ ; 18/1/34212//(BHF) Centre of Research Excellence/ ; }, mesh = {Humans ; *COVID-19/immunology/complications ; Female ; Male ; Middle Aged ; Prospective Studies ; Adult ; *Magnetic Resonance Imaging ; SARS-CoV-2/immunology ; Myocardium/pathology/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Edema, Cardiac/diagnostic imaging/immunology/pathology ; Predictive Value of Tests ; Aged ; }, abstract = {AIMS: While acute cardiovascular complications of coronavirus disease 2019 (COVID-19) are well described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19.

METHODS AND RESULTS: Twenty-one participants {mean age 47 [standard deviation (SD) 13] years, 71% female} with long COVID-19 (n = 17), raised troponin (n = 2), or unexplained new-onset heart failure (n = 2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment, were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers were performed. Nine of the 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and two had severe left ventricular (LV) impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23, and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αβ cells showed higher proportions of cytotoxic granzyme B+(GZB+)-secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a least absolute shrinkage and selection operator regression model (composite area under the curve 0.96, 95% confidence interval 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r = 0.47, P = 0.04).

CONCLUSION: COVID-19-related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.}, } @article {pmid39073192, year = {2024}, author = {Deng, X and Cui, H and Liang, H and Wang, X and Yu, H and Wang, J and Wang, W and Liu, D and Zhang, Y and Dong, E and Tang, Y and Xiao, H}, title = {SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID.}, journal = {Journal of internal medicine}, volume = {296}, number = {3}, pages = {291-297}, doi = {10.1111/joim.20000}, pmid = {39073192}, issn = {1365-2796}, support = {2021YFF0501401//National Key Research and Development Program of China/ ; 2023YFA1800902//National Key Research and Development Program of China/ ; 81830009//National Natural Science Foundation of China/ ; 82030072//National Natural Science Foundation of China/ ; 82070235//National Natural Science Foundation of China/ ; 82300295//National Natural Science Foundation of China/ ; 2021-I2M-5-003//CAMS Innovation Fund for Medical Sciences/ ; 22HHXBSS00007//Haihe Laboratory of Cell Ecosystem Innovation Fund/ ; }, mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/complications/metabolism ; Male ; *SARS-CoV-2 ; Female ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Aged ; Molecular Docking Simulation ; Myocytes, Cardiac/metabolism/drug effects ; Adrenergic beta-Agonists/pharmacology/therapeutic use ; }, abstract = {BACKGROUND: Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown.

METHODS AND RESULTS: Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β1- and β2-AR, but not to D1-dopamine receptor. These interactions were blocked by β1- and β2-AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs.

CONCLUSION: Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS.}, } @article {pmid39071772, year = {2024}, author = {Polizzi, J and Tosto-Mancuso, J and Tabacof, L and Wood, J and Putrino, D}, title = {Resonant breathing improves self-reported symptoms and wellbeing in people with Long COVID.}, journal = {Frontiers in rehabilitation sciences}, volume = {5}, number = {}, pages = {1411344}, pmid = {39071772}, issn = {2673-6861}, abstract = {INTRODUCTION: Long COVID involves debilitating symptoms, many of which mirror those observed with dysautonomia, and care must be taken with rehabilitation for autonomic dysfunction to avoid post-exertional malaise/post-exertional symptom exacerbation. Resonant breathing (breathing slowly at a defined rate of breaths per minute) requires less exertion and can potentially improve autonomic function. The objective of this work was to report on the impact of a resonant breathing program on self-reported symptoms and wellbeing in people with Long COVID.

METHODS: A retrospective analysis of de-identified data was completed in a convenience sample of people with Long COVID, who participated in the Meo Health (formerly known as Stasis HP) resonant breathing program. Participants completed baseline and follow up surveys.

RESULTS: Data were available for 99 participants. Most measures of symptoms and wellbeing improved at follow up, with the largest differences per participant seen in sense of wellness (47.3%, p < 0.0001), ability to focus (57.5%, p < 0.0001), ability to breathe (47.5%, p < 0.0001), ability to control stress (61.8%, p < 0.0001) and sleep quality (34.9%, p = 0.0002). Most (92%) participants reported improvement at follow up on the Patient Global Impression of Change Scale.

CONCLUSION: Self-reported symptoms and wellbeing improved in people with Long COVID completing resonant breathing. Resonant breathing can be considered as an option within the broader treatment plan of people with Long COVID.}, } @article {pmid39070174, year = {2024}, author = {Zhou, J and Li, X and Zhang, T and Liu, Z and Li, P and Yu, N and Wang, W}, title = {Pre-existing sleep disturbances and risk of COVID-19: a meta-analysis.}, journal = {EClinicalMedicine}, volume = {74}, number = {}, pages = {102719}, pmid = {39070174}, issn = {2589-5370}, abstract = {BACKGROUND: Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19.

METHODS: We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518).

FINDINGS: A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07-1.18), hospitalization (OR = 1.25, 95% CI 1.15-1.36), mortality (OR = 1.45, 95% CI 1.19-1.78), and long COVID (OR = 1.36 95% CI 1.17-1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia.

INTERPRETATION: Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19.

FUNDING: The National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province.}, } @article {pmid39069361, year = {2024}, author = {Gott, D and Orsillo, K and Ticotsky, A}, title = {Connecting the Dots: Unveiling the Overlapping Realities of Long Coronavirus Disease and Post-Intensive Care Syndrome.}, journal = {Critical care nursing clinics of North America}, volume = {36}, number = {3}, pages = {427-436}, doi = {10.1016/j.cnc.2023.12.006}, pmid = {39069361}, issn = {1558-3481}, mesh = {Humans ; *COVID-19 ; Intensive Care Units ; Post-Acute COVID-19 Syndrome ; Critical Care Nursing ; Critical Care ; Critical Illness ; }, abstract = {Critical care areas saw an unprecedented number of patients throughout the coronavirus disease 2019 (COVID-19) pandemic. Unfortunately, many of these patients continue to experience lingering symptoms long after their discharge from the intensive care unit, related to post-intensive care syndrome and/or post-acute sequelae of COVID-19. Nurses should be aware of these often invisible illnesses and attentive to the fact that this patient population requires ongoing support via multidisciplinary, coordinated care.}, } @article {pmid39069330, year = {2024}, author = {Okuducu, YK and Mall, MA and Yonker, LM}, title = {COVID-19 in Pediatric Populations.}, journal = {Clinics in chest medicine}, volume = {45}, number = {3}, pages = {675-684}, doi = {10.1016/j.ccm.2024.02.019}, pmid = {39069330}, issn = {1557-8216}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Child ; *SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/epidemiology/therapy ; Child, Preschool ; Risk Factors ; Age Factors ; }, abstract = {The COVID-19 pandemic reshaped the landscape of respiratory viral illnesses, causing common viruses to fade as SARS-CoV-2 took precedence. By 2023, more than 96% of the children in the United States were estimated to have been infected with SARS-CoV-2, with certain genetic predispositions and underlying health conditions posing risk factors for severe disease in children. Children, in general though, exhibit immunity advantages, protecting against aspects of the SARS-CoV-2 infection known to drive increased severity in older adults. Post-COVID-19 complications such as multisystem inflammatory syndrome in children and long COVID have emerged, underscoring the importance of vaccination. Here, we highlight the risks of severe pediatric COVID-19, age-specific immunoprotection, comparisons of SARS-CoV-2 with other respiratory viruses, and factors contributing to post-COVID-19 complications in children.}, } @article {pmid39069199, year = {2024}, author = {Zhou, T and Sawano, M and Arun, AS and Caraballo, C and Michelsen, T and McAlpine, LS and Bhattacharjee, B and Lu, Y and Khera, R and Huang, C and Warner, F and Herrin, J and Iwasaki, A and Krumholz, HM}, title = {Internal Tremors and Vibrations in Long COVID: A Cross-Sectional Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.07.008}, pmid = {39069199}, issn = {1555-7162}, abstract = {BACKGROUND: Internal tremors and vibrations are symptoms previously described as part of neurologic disorders but not fully described as a part of long COVID. This study compared pre-pandemic comorbidities, new-onset conditions, and long COVID symptoms between people with internal tremors and vibrations as part of their long COVID symptoms and people with long COVID but without these symptoms.

METHODS: The Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study surveyed 423 adults who had long COVID between May 12, 2022 and June 1, 2023. The exposure variable was long COVID symptoms of internal tremors and vibrations. The outcome variables were demographic characteristics, pre-pandemic comorbidities, new-onset conditions, other symptoms, and quality of life.

RESULTS: Among study participants with long COVID, median age was 46 years (IQR, 38-56), 74% were female, 87% were Non-Hispanic White, and 158 (37%) reported "internal tremors, or buzzing/vibration" as a long COVID symptom. The two groups reported similar pre-pandemic comorbidities, but participants with internal tremors reported worse health as measured by the Euro-QoL visual analogue scale (median: 40 points [IQR, 30-60] vs. 50 points [IQR, 35-62], P = .007) and had higher rates of new-onset mast cell disorders (11% [95% CI, 7.1-18] vs. 2.6% [1.2-5.6], P = .008) and neurologic conditions (22% [95% CI, 16-29] vs. 8.3% [5.4-12], P = .004).

CONCLUSIONS: Among people with long COVID, those with internal tremors and vibrations had different conditions and symptoms and worse health status compared with others who had long COVID without these symptoms.}, } @article {pmid39067516, year = {2024}, author = {Li, H and Wang, X and Zeng, G}, title = {Re: 'The efficacy of antivirals, corticosteroids, and monoclonal antibodies as acute COVID-19 treatments in reducing the incidence of long COVID-19' by Sun et al.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {12}, pages = {1616-1617}, doi = {10.1016/j.cmi.2024.07.016}, pmid = {39067516}, issn = {1469-0691}, } @article {pmid39066303, year = {2024}, author = {Maham, S and Yoon, MS}, title = {Clinical Spectrum of Long COVID: Effects on Female Reproductive Health.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066303}, issn = {1999-4915}, support = {No. HV22C0128//the Korea Health Industry Development Institute (KHIDI)/ ; GCU-202103040001//Gachon University Research Fund of 2020/ ; }, mesh = {Humans ; Female ; *COVID-19/epidemiology/virology/immunology ; *Reproductive Health ; *SARS-CoV-2 ; Menstrual Cycle ; Post-Acute COVID-19 Syndrome ; Fertility ; }, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on the impact of SARS-CoV-2 on the menstrual cycle, ovarian function, fertility, and overall gynecological health. This study emphasizes the role of angiotensin-converting enzyme receptors in viral entry and the subsequent tissue-specific pathological effects. It also explores the potential influence of long COVID on hormonal balance and immune responses, contributing to menstrual irregularities and impaired ovarian function. The findings indicate a higher prevalence of long-term COVID-19 among women, highlighting the substantial implications for reproductive health and the need for sex-sensitive longitudinal studies. Enhanced surveillance and targeted research are essential to develop effective interventions that prioritize women's reproductive well-being following SARS-CoV-2 infection. This review advocates for a sex-informed approach to ongoing COVID-19 research and healthcare strategies, aiming to provide up-to-date and pertinent data for healthcare providers and the general public, ultimately improving outcomes for females affected by long COVID.}, } @article {pmid39066250, year = {2024}, author = {Durieux, JC and Zisis, SN and Mouchati, C and Labbato, D and Abboud, M and McComsey, GA}, title = {Sex Modifies the Effect of COVID-19 on Arterial Elasticity.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066250}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/physiopathology ; Female ; Male ; Middle Aged ; *SARS-CoV-2 ; Sex Factors ; Adult ; Aged ; Elasticity ; Vascular Stiffness ; Arteries/physiopathology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Fibrin Fibrinogen Degradation Products/analysis ; }, abstract = {There is limited long-term evidence on the effects of COVID-19 on vascular injury between male and female sex. An adult cohort of COVID-19 survivors (COVID+) and confirmed SARS-CoV-2 antibody-negative participants (COVID-) were prospectively enrolled. COVID+ participants who have documented the presence of persistent symptoms four weeks following infection were considered to have post-acute sequelae of COVID-19 (PASC). Non-invasive, FDA-approved EndoPAT (Endo-PAT2000) was used for endothelial assessment. COVID-(n = 94) were 1:1 propensity score matched to COVID+ (n = 151) on baseline covariates including sex. Among COVID+, 66.2% (n = 100) had PASC. Higher levels of coagulation marker, D-dimer (p = 0.001), and gut permeability marker, zonulin (p = 0.001), were associated with female sex. Estimated differences in augmentation index (AI) between COVID- (0.9 ± 17.2) and COVID+ (8.4 ± 15.7; p = 0.001) and between female and male sex (12.9 ± 1.9; p < .0001) were observed. Among COVID+ with PASC, the average AI (10.5 ± 1.6) was 9.7 units higher than COVID- (p < .0001) and 6.2 units higher compared to COVID+ with no PASC (p = 0.03). COVID+ PASC+ female sex had the highest AI (14.3 ± 1.9). The effects of SARS-CoV-2 infection on vascular function varies across strata of sex and female sex in the post-acute phase of COVID-19 have the worse arterial elasticity (highest AI).}, } @article {pmid39066223, year = {2024}, author = {Donald, J and Bilasy, SE and Yang, C and El-Shamy, A}, title = {Exploring the Complexities of Long COVID.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066223}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Risk Factors ; Comorbidity ; Prevalence ; Female ; Male ; Dysbiosis ; }, abstract = {Since the emergence of the SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 million deaths have been reported globally. Despite most individuals recovering within four weeks, the Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such as age, gender, comorbidities, initial COVID-19 severity, and vaccine interactions, and delves into potential mechanisms, including immune responses, viral persistence, and gut dysbiosis. Moreover, we conclude that women, advanced age, comorbidities, non-vaccination, and low socioeconomic status all appear to be risk factors. The reasons for these differences are still not fully understood and likely involve a complex relationship between social, genetic, hormonal, and other factors. Furthermore, individuals with Long COVID-19 seem more likely to endure economic hardship due to persistent symptoms. In summary, our findings further illustrate the multifaceted nature of Long COVID and underscore the importance of understanding the epidemiological factors and potential mechanisms needed to develop effective therapeutic strategies and interventions.}, } @article {pmid39066191, year = {2024}, author = {Arango-Ibanez, JP and Córdoba-Melo, BD and Gutiérrez Posso, JM and Barbosa-Rengifo, MM and Herrera, CJ and Quintana Da Silva, MA and Buitrago, AF and Coronel Gilio, ML and Pow-Chong-Long, F and Gómez-Mesa, JE}, title = {Long COVID Clusters of Symptoms Persist beyond Two Years after Infection: Insights from the CARDIO COVID 20-21 Registry.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066191}, issn = {1999-4915}, support = {TQ-2021-1756//Tecnoquimicas S.A./ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Middle Aged ; Female ; Aged ; *Fatigue/etiology ; *SARS-CoV-2 ; *Myalgia/etiology/physiopathology ; *Registries ; *Post-Acute COVID-19 Syndrome ; *Arthralgia/virology/etiology ; Prospective Studies ; Prevalence ; Cluster Analysis ; Ageusia/epidemiology/etiology/virology ; Anosmia/epidemiology/etiology ; Dyspnea/physiopathology/virology/etiology ; Follow-Up Studies ; Cough ; Time Factors ; Cohort Studies ; }, abstract = {Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.}, } @article {pmid39066184, year = {2024}, author = {Vu, TT and Nguyen, KC and Nguyen, HT and Hoang, A and Ngu, ND and Tran, DN and Phan, HB and Nguyen, HTT and Pham, TQ and Vogt, F}, title = {Prevalence and Symptom Profile of Long COVID among Schoolchildren in Vietnam.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066184}, issn = {1999-4915}, support = {NA//The Australian National University/ ; }, mesh = {Humans ; Vietnam/epidemiology ; Child ; *COVID-19/epidemiology ; Adolescent ; Female ; Male ; Prevalence ; Cross-Sectional Studies ; *SARS-CoV-2 ; *Quality of Life ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is a recognized condition that can follow SARS-CoV-2 infection. It has been primarily observed and studied in adults. Evidence on long COVID among children is scarce. We aimed to estimate its prevalence and symptom profile among schoolchildren, and its effects on studying, daily activities, and quality of life.

METHODS: We conducted a cross-sectional online survey among caregivers of 2226 schoolchildren aged 12-17 in Thai Nguyen, Vietnam, from 11 April to 16 May 2023 using WHO definitions and a validated quality of life questionnaire.

RESULTS: Among 1507 children with confirmed SARS-CoV-2 infection ≥ 5 months prior, 85 (5.6%) had long COVID. Memory loss (85.9%), poor concentration capacity (58.8%), and fatigue (57.6%) were their most common symptoms. They reported more frequent interference with their studies, observed differences in school absence rates, reduced daily activities, worsened overall health status, and relatively higher utilization of health services compared with children who only suffered from acute COVID-19 symptoms after infection.

CONCLUSIONS: Given the near-ubiquitous exposure to SARS-CoV-2 among children at this stage of the pandemic, our findings contribute invaluable evidence of an emerging public health burden among the pediatric population in Vietnam and globally. Concerted public health measures are needed to reduce long-term impacts on health, education, and wellbeing.}, } @article {pmid39065072, year = {2024}, author = {Fernández-de-Las-Peñas, C and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Torres-Macho, J and Ryan-Murua, P and Franco-Moreno, A and Pellicer-Valero, OJ and Arendt-Nielsen, L and Giordano, R}, title = {DNA Methylation Levels of the ACE2 Promoter Are Not Associated with Post-COVID-19 Symptoms in Individuals Who Had Been Hospitalized Due to COVID-19.}, journal = {Microorganisms}, volume = {12}, number = {7}, pages = {}, pmid = {39065072}, issn = {2076-2607}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {It is known that SARS-CoV-2 can translocate via membrane ACE2 exopeptidase into the host cells, and thus hypomethylation of ACE2 possibly upregulates its expression, enhancing the risk of SARS-CoV-2 infection. This study investigated if DNA methylation levels of the ACE2 promoter are associated with the development of post-COVID-19 symptomatology in a cohort of COVID-19 survivors who had been previously hospitalized. Non-stimulated saliva samples were obtained from 279 (51.5 male, mean age: 56.5 ± 13.0 years old) COVID-19 survivors who were hospitalized during the first wave of the pandemic. A face-to-face interview in which patients described the presence of post-COVID-19 symptoms (defined as a symptom that started no later than three months after SARS-CoV-2 infection) that they suffered from to an experienced healthcare trainer was conducted. Methylation of five CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. The percentage of methylation (%) was associated with the presence of the following reported post-COVID-19 symptoms: fatigue, dyspnea at rest, dyspnea at exertion, brain fog, memory loss, concentration loss, or gastrointestinal problems. Participants were assessed a mean of 17.8 (SD: 5.3) months after hospitalization. At that time, 88.1% of the patients experienced at least one post-COVID-19 symptom (mean number for each patient: 3.0; SD: 1.9 post-COVID-19 symptoms). Dyspnea at exertion (67.3%), fatigue (62.3%), and memory loss (31.2%) were the most frequent post-COVID-19 symptoms in the sample. Overall, the analysis did not reveal any difference in the methylation of the ACE2 promoter in any of the CpG locations according to the presence or absence of fatigue, dyspnea at rest, dyspnea at exertion, memory loss, brain fog, concentration loss, and gastrointestinal problems. This study did not find an association between methylation of ACE2 promoter and the presence of post-COVID-19 fatigue, dyspnea, cognitive or gastrointestinal problems in previously hospitalized COVID-19 survivors.}, } @article {pmid39064240, year = {2024}, author = {De Luca, R and Bonanno, M and Maggio, MG and Todaro, A and Rifici, C and Mento, C and Muscatello, MRA and Castorina, MV and Tonin, P and Quartarone, A and Pugliese, ME and Calabrò, RS}, title = {Compassion Fatigue in a Cohort of South Italian Nurses and Hospital-Based Clinical Social Workers Following COVID-19: A Cross-Sectional Survey.}, journal = {Journal of clinical medicine}, volume = {13}, number = {14}, pages = {}, pmid = {39064240}, issn = {2077-0383}, support = {//Current Research Funds, 2024, Ministry of Health, Italy/ ; }, abstract = {Background/Objective: The COVID-19 pandemic has led to a significant increase in the workloads of healthcare workers (HCWs). The fear of contracting the new virus with the frequent medical consequences has affected their mental health. As a result, they are at high risk of compassion fatigue (CF). In this multicentric study, as a primary objective, we evaluate the incidence and/or prevalence of CF in a cohort of Italian nurses and HCWs (hospital-based clinical social workers of neurological patients) who have contracted SARS-CoV-2 infection. Our secondary aim is to evaluate the difference in experiencing CF between subjects with and without long-term COVID. Methods: In this study, 101 HCWs attending three different neurorehabilitation settings (the Neurorehabilitation Unit of the "Bonino Pulejo" Neurolesi Center of Messina, the Neurorehabilitation Department of Crotone, and the Psychiatric Unit of the University Hospital of Messina) were enrolled from May 2021 to May 2023. Data were collected through self-administered semi-structured interviews. Results: We observed high percentages of CF difficulties in both nurses and HCWs, related to mood alteration in 57.7%, headaches in 44.4%, and fatigue in 62%. Higher percentages were found in individuals with long-term COVID-19, including mood alteration in 93.9%, headache in 88.6%, and memory-related problems in 98.5%. Conclusions: The complexity of a patient's care pathway, especially in chronic disease situations, requires an enormous commitment that can lead to burnout and CF, which should be considered to initiate preventive interventions aimed at helping "those who help", for the well-being of patients, healthcare teams, and healthcare organizations.}, } @article {pmid39064183, year = {2024}, author = {Vontetsianos, A and Chynkiamis, N and Gounaridi, MI and Anagnostopoulou, C and Lekka, C and Zaneli, S and Anagnostopoulos, N and Oikonomou, E and Vavuranakis, M and Rovina, N and Papaioannou, AI and Kaltsakas, G and Koulouris, N and Vogiatzis, I}, title = {Exercise Intolerance Is Associated with Cardiovascular Dysfunction in Long COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {13}, number = {14}, pages = {}, pmid = {39064183}, issn = {2077-0383}, abstract = {Background/Objectives: Cardiorespiratory complications are commonly reported among patients with long COVID-19 syndrome. However, their effects on exercise capacity remain inconclusive. We investigated the impact of long COVID-19 on exercise tolerance combining cardiopulmonary exercise testing (CPET) with resting echocardiographic data. Methods: Forty-two patients (55 ± 13 years), 149 ± 92 days post-hospital discharge, and ten healthy age-matched participants underwent resting echocardiography and an incremental CPET to the limit of tolerance. Left ventricular global longitudinal strain (LV-GLS) and the left ventricular ejection fraction (LVEF) were calculated to assess left ventricular systolic function. The E/e' ratio was estimated as a surrogate of left ventricular end-diastolic filling pressures. Tricuspid annular systolic velocity (SRV) was used to assess right ventricular systolic performance. Through tricuspid regurgitation velocity and inferior vena cava diameter, end-respiratory variations in systolic pulmonary artery pressure (PASP) were estimated. Peak work rate (WRpeak) and peak oxygen uptake (VO2peak) were measured via a ramp incremental symptom-limited CPET. Results: Compared to healthy participants, patients had a significantly (p < 0.05) lower LVEF (59 ± 4% versus 49 ± 5%) and greater left ventricular end-diastolic diameter (48 ± 2 versus 54 ± 5 cm). In patients, there was a significant association of E/e' with WRpeak (r = -0.325) and VO2peak (r = -0.341). SRV was significantly associated with WRpeak (r = 0.432) and VO2peak (r = 0.556). LV-GLS and PASP were significantly correlated with VO2peak (r = -0.358 and r = -0.345, respectively). Conclusions: In patients with long COVID-19 syndrome, exercise intolerance is associated with left ventricular diastolic performance, left ventricular end-diastolic pressure, PASP and SRV. These findings highlight the interrelationship of exercise intolerance with left and right ventricular performance in long COVID-19 syndrome.}, } @article {pmid39064139, year = {2024}, author = {Yokoyama, S and Honda, H and Otsuka, Y and Tokumasu, K and Nakano, Y and Sakurada, Y and Matsuda, Y and Sunada, N and Hasegawa, T and Takase, R and Omura, D and Soejima, Y and Ueda, K and Kishida, M and Otsuka, F}, title = {Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan.}, journal = {Journal of clinical medicine}, volume = {13}, number = {14}, pages = {}, pmid = {39064139}, issn = {2077-0383}, support = {23fk0108585h0001//Japan Agency for Medical Research and Development/ ; }, abstract = {Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m[2]; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID.}, } @article {pmid39063618, year = {2024}, author = {Cerfoglio, S and Verme, F and Capodaglio, P and Rossi, P and Cvetkova, V and Boldini, G and Galli, M and Cimolin, V}, title = {Motor and Respiratory Tele-Rehabilitation in Patients with Long COVID-19 after Hospital Discharge: An Interventional Study.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {39063618}, issn = {2075-1729}, abstract = {The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for individuals with long COVID-19 after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e., baseline, at discharge from in-hospital rehabilitation and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Additionally, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p < 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that the proposed home-based tele-rehabilitation shows potential in enhancing motor and respiratory function in patients with long COVID. Despite limitations such as the small sample size, lack of control group and the preliminary nature of the outcomes observed, the overall findings seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Nevertheless, further research is needed to validate these findings and explore tele-rehabilitation's potential in broader and different patient populations.}, } @article {pmid39063534, year = {2024}, author = {D'Souza, AN and Merrett, M and Griffin, H and Tran-Duy, A and Struck, C and Fazio, TN and Juj, G and Granger, CL and Peiris, CL}, title = {Recovering from COVID-19 (ReCOV): Feasibility of an Allied-Health-Led Multidisciplinary Outpatient Rehabilitation Service for People with Long COVID.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {7}, pages = {}, pmid = {39063534}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/rehabilitation ; Female ; Male ; Middle Aged ; *Feasibility Studies ; Adult ; SARS-CoV-2 ; Cohort Studies ; Outpatients/statistics & numerical data ; Patient Care Team ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: A multidisciplinary approach is required for the management of long COVID. The aim of this study was to determine the feasibility (demand, implementation, practicality, acceptability, and limited efficacy) of an allied-health-led multidisciplinary symptom management service (ReCOV) for long COVID.

METHODS: A single-group observational cohort feasibility study was conducted to determine demand (referrals), acceptability (survey), implementation (waitlist times, health professions seen), practicality (adverse events), and limited efficacy (admission and discharge scores from the World Health Organization Disability Assessment Scale, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire, and EuroQol 5D-5L). Data are presented as median [interquartile range] or count (percentage).

RESULTS: During the study, 143 participants (aged 42.00 [32.00-51.00] years, 68% women) participated in ReCOV. Participants were waitlisted for 3.86 [2.14-9.86] weeks and engaged with 5.00 [3.00-6.00] different health professionals. No adverse events occurred. The thematic analysis revealed that ReCOV was helpful but did not fully meet the needs of all participants. Limited efficacy testing indicated that participants had improved understanding and control (p < 0.001) of symptoms (BIPQ) and a small improvement in EQ VAS score (median difference 5.50 points [0.00-25.00], p = 0.004]).

CONCLUSIONS: A multidisciplinary service was safe and mostly acceptable to participants for the management of long COVID. Further research should investigate the clinical and cost effectiveness of such a service, including optimal service duration and patient outcomes.}, } @article {pmid39062904, year = {2024}, author = {Pacheco-García, U and Varela-López, E and Serafín-López, J}, title = {Immune Stimulation with Imiquimod to Best Face SARS-CoV-2 Infection and Prevent Long COVID.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062904}, issn = {1422-0067}, support = {Not applied//Instituto Nacional de Cardiología Ignacio Chávez/ ; Not Applied//Instituto Nacional de Cardiología Ignacio Chávez/ ; }, mesh = {Humans ; *Imiquimod ; *COVID-19/immunology/prevention & control/complications ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Adjuvants, Immunologic/therapeutic use ; Cytokines/metabolism ; COVID-19 Vaccines/immunology ; }, abstract = {Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus and accelerated recovery times for those infected. Nonetheless, a significant demographic, comprising around 20% to 30% of the adult population, remains unimmunized due to diverse factors. Furthermore, alongside those recovered from the infection, there is a subset of the population experiencing persistent symptoms referred to as Long COVID. This condition is more prevalent among individuals with underlying health conditions and immune system impairments. Some Long COVID pathologies stem from direct damage inflicted by the viral infection, whereas others arise from inadequate immune system control over the infection or suboptimal immunoregulation. There are differences in the serum cytokines and miRNA profiles between infected individuals who develop severe COVID-19 or Long COVID and those who control adequately the infection. This review delves into the advantages and constraints associated with employing imiquimod in human subjects to enhance the immune response during SARS-CoV-2 immunization. Restoration of the immune system can modify it towards a profile of non-susceptibility to SARS-CoV-2. An adequate immune system has the potential to curb viral propagation, mitigate symptoms, and ameliorate the severe consequences of the infection.}, } @article {pmid39062780, year = {2024}, author = {Wei, L and Song, L and Dunker, AK and Foster, JA and Uversky, VN and Goh, GK}, title = {A Comparative Experimental and Computational Study on the Nature of the Pangolin-CoV and COVID-19 Omicron.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062780}, issn = {1422-0067}, support = {32161143027//National Natural Science Foundation of China/ ; }, mesh = {*SARS-CoV-2/pathogenicity ; Animals ; *COVID-19/virology/transmission ; *Pangolins/virology ; Humans ; Intrinsically Disordered Proteins/metabolism/chemistry ; Coronavirus Nucleocapsid Proteins/metabolism ; Computational Biology/methods ; Phosphoproteins ; }, abstract = {The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have an abnormally hard outer shell (low M disorder, i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far has been found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2, especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 and later in Omicron, is associated with attenuation according to the Shell-Disorder Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.}, } @article {pmid39062549, year = {2024}, author = {Ashmawy, R and Hammouda, EA and El-Maradny, YA and Aboelsaad, I and Hussein, M and Uversky, VN and Redwan, EM}, title = {Interplay between Comorbidities and Long COVID: Challenges and Multidisciplinary Approaches.}, journal = {Biomolecules}, volume = {14}, number = {7}, pages = {}, pmid = {39062549}, issn = {2218-273X}, mesh = {Humans ; *COVID-19/epidemiology/immunology ; *Comorbidity ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology ; }, abstract = {Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.}, } @article {pmid39062061, year = {2024}, author = {Saloň, A and De Boever, P and Goswami, N}, title = {Microvascular Changes during Viral Infections: A Systematic Review of Studies Using Retinal Vessel Diameter Assessments.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062061}, issn = {2227-9059}, abstract = {Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical non-invasive method to assess the structure and function of the retinal microcirculation, a proxy for the microcirculatory system, retinal fundus imaging can be used. We examined the impact of viral infections on retinal vessel diameters and performed a systematic analysis of the literature. Our search was carried out on PubMed using predefined search queries. After a methodological filtering process, we were able to reduce the corpus of 363 publications to 16 studies that met the search parameters. We used a narrative review style to summarise the observations. Six studies covered COVID-19, seven described HIV, and three were included in the subgroup called others, covering viruses, such as Dengue Fever and Crimean-Congo Haemorrhagic Fever. Analysis of the literature showed that viral infections are associated with alterations in the retinal vessels' vasoactivity. COVID-19 and other infections cause inflammation-associated the vasodilatation of microvasculature as a short-term effect of the infection. Long COVID-19 as well as HIV are the cause of chronic inflammation impacting microvascular morphology via retinal vessel diameter narrowing. The review emphasises the importance of the understudied area of viral infections' effects on retinal microcirculation. Continuous research in this area is needed to further verify retinal fundus imaging as an innovative tool for the optimal diagnosis of microvascular changes. As changes in the microvasculature precede changes in bigger arteries, the early detection of microvascular changes can go a long way in reducing the morbidity and mortality associated with cardiovascular diseases.}, } @article {pmid39062021, year = {2024}, author = {Nuguri, SM and Hackshaw, KV and Castellvi, SL and Wu, Y and Gonzalez, CM and Goetzman, CM and Schultz, ZD and Yu, L and Aziz, R and Osuna-Diaz, MM and Sebastian, KR and Brode, WM and Giusti, MM and Rodriguez-Saona, L}, title = {Surface-Enhanced Raman Spectroscopy Combined with Multivariate Analysis for Fingerprinting Clinically Similar Fibromyalgia and Long COVID Syndromes.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062021}, issn = {2227-9059}, support = {R61NS117211//National Institute of Health/ ; GR122808//National Institute of Health/ ; CHE-2117225//National Science Foundation/ ; }, abstract = {Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC share similarities with regard to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface-enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCAs) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n = 48 FM and n = 46 LC) and volumetric absorptive micro-sampling tips (VAMS, n = 39 FM and n = 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra were acquired using SERS with gold nanoparticles (AuNPs). Soft independent modelling of class analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity, achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNP SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.}, } @article {pmid39062017, year = {2024}, author = {Homma, ST and Wang, X and Frere, JJ and Gower, AC and Zhou, J and Lim, JK and tenOever, BR and Zhou, L}, title = {Respiratory SARS-CoV-2 Infection Causes Skeletal Muscle Atrophy and Long-Lasting Energy Metabolism Suppression.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062017}, issn = {2227-9059}, support = {R21 AR081655/AR/NIAMS NIH HHS/United States ; T32 GM146636/GM/NIGMS NIH HHS/United States ; 5R21AR081655-02//National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; UL1TR001430//National Institutes of Health, Clinical and Translational Science Award/ ; }, abstract = {Muscle fatigue represents the most prevalent symptom of long-term COVID, with elusive pathogenic mechanisms. We performed a longitudinal study to characterize histopathological and transcriptional changes in skeletal muscle in a hamster model of respiratory SARS-CoV-2 infection and compared them with influenza A virus (IAV) and mock infections. Histopathological and bulk RNA sequencing analyses of leg muscles derived from infected animals at days 3, 30, and 60 post-infection showed no direct viral invasion but myofiber atrophy in the SARS-CoV-2 group, which was accompanied by persistent downregulation of the genes related to myofibers, ribosomal proteins, fatty acid β-oxidation, tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation complexes. While both SARS-CoV-2 and IAV infections induced acute and transient type I and II interferon responses in muscle, only the SARS-CoV-2 infection upregulated TNF-α/NF-κB but not IL-6 signaling in muscle. Treatment of C2C12 myotubes, a skeletal muscle cell line, with combined IFN-γ and TNF-α but not with IFN-γ or TNF-α alone markedly impaired mitochondrial function. We conclude that a respiratory SARS-CoV-2 infection can cause myofiber atrophy and persistent energy metabolism suppression without direct viral invasion. The effects may be induced by the combined systemic interferon and TNF-α responses at the acute phase and may contribute to post-COVID-19 persistent muscle fatigue.}, } @article {pmid39061679, year = {2024}, author = {Ursescu, C and Teodoru, G and Bucurica, S and Nica, RI and Lazăr, ȘD and Popescu, MN and Ciobanu, I and Berteanu, M}, title = {Using the ClinFIT COVID-19 Instrument to Assess the Functional Impairments Specific to Post-COVID-19 Patients in Romania.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {14}, pages = {}, pmid = {39061679}, issn = {2075-4418}, support = {Publish not perish//Carol Davila University of Medicine and Pharmacy/ ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has led to approximately 3.5 million cases in Romania, causing systemic inflammation and over 200 symptoms affecting various body systems. This complexity has challenged rehabilitation systems, necessitating personalized plans tailored to each patient's illness stage and impairment level. The ISPRM-developed ClinFIT COVID-19 instrument, aligned with the ICF categories, assists in assessing patients during acute, post-acute, and long-term phases.

OBJECTIVE: This study aimed to evaluate and assess functional impairments in post-COVID-19 patients in Romania, with a secondary goal of generating rehabilitation directions.

METHODS: Data were collected from patients at two Bucharest medical centers, including those with persistent symptoms post-acute phase. Participants were assessed using the adapted ClinFIT COVID-19 instrument, and descriptive statistics were applied.

CONCLUSIONS: Findings revealed diverse functional impairments in physical, psychological, and social domains among post-COVID-19 patients, with severe impairments more common in those with long-term COVID-19. Complete impairment in complex movement and paid work was noted, affecting one-third of salaried employees and forcing some to retire. In the acute phase, the most frequent functional impairments were sleep, attention, pain sensation, and exercise tolerance functions. In contrast, the most severely affected functions were exercise tolerance and mobility joint functions. Age did not positively correlate with any of the analyzed functions. In the post-acute phase, sleep, energy, and drive functions remained the most frequently affected functions, while the most severely affected was, by far, the moving around function. In the post-acute period, respiratory and respiratory muscle functions strongly correlated with all tasks related to physical activity. In the long COVID-19 phase, remunerative employment was the most severely affected function, while attention functions remained the most frequently affected, similar to the acute phase. The ClinFIT COVID-19 instrument effectively captured these impairments, underscoring the need for comprehensive rehabilitation strategies.}, } @article {pmid39061051, year = {2024}, author = {Askarian, M and Taherifard, E and Jazzabi, F and Shayan, Z and Assadian, O and Groot, G and Hatam, N and Askarian, A and Faghihi, SM and Taherifard, E}, title = {Epidemiological and clinical characteristics of long COVID-19 among Iranians: A community-based study in southern Iran.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {2007}, pmid = {39061051}, issn = {1471-2458}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Incidence ; Iran/epidemiology ; Middle Eastern People ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: The study aimed to evaluate the prevalence and pattern of long COVID-19 (LC) symptoms among individuals who had contracted COVID-19, to calculate the incidence of LC, and to provide insights into risk factors associated with developing LC in this population.

METHODS: This population-based cross-sectional survey was conducted in Fars province in 2023. Adult participants with a history of COVID-19 were recruited using a cluster random sampling method, alongside a control group with similar characteristics through the same methodology. Data were collected through in-person interviews using two researcher-developed data collection forms focused on demographic and clinical information.

RESULTS: A total of 2010 participants, comprising 1561 (77.7%) and 449 (22.3%) individuals with and without a previous history of COVID-19 were included. Among those with COVID-19 history, the prevalence of experiencing any symptoms was 93.7% (95% CI of 92.3%-94.8%) during the disease acute phase and 36.4% (95% CI of 34.0%-38.8%) after recovery. The incidence of symptoms specifically related to COVID-19, calculated by comparing the symptom rates between participants with and without a history of COVID-19, was found to be 13%. Factors such as older age, previous hospitalization for COVID-19, presence of cardiovascular disease, and use of steroids/chemotherapy were associated with LC symptoms.

CONCLUSIONS: Our investigation sheds light on long-term aspects of COVID-19, demonstrating a significant prevalence of LC with diverse manifestations. It also underscores the importance of establishing standardized criteria and control groups in research on LC to address challenges related to heterogeneity and potential overestimation of symptoms.}, } @article {pmid39061026, year = {2024}, author = {Venkatraman, S and Salinero, JMG and Scheinfeld, A and Houghton, S and Redmond, D and Safford, M and Rajan, M}, title = {Clusters of long COVID among patients hospitalized for COVID-19 in New York City.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1994}, pmid = {39061026}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; New York City/epidemiology ; Male ; Female ; *Hospitalization/statistics & numerical data ; Middle Aged ; Cluster Analysis ; *Social Isolation/psychology ; Aged ; *Loneliness/psychology ; Adult ; Post-Acute COVID-19 Syndrome ; Unsupervised Machine Learning ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Recent studies have demonstrated that individuals hospitalized due to COVID-19 can be affected by "long-COVID" symptoms for as long as one year after discharge.

OBJECTIVES: Our study objective is to identify data-driven clusters of patients using a novel, unsupervised machine learning technique.

METHODS: The study uses data from 437 patients hospitalized in New York City between March 3rd and May 15th of 2020. The data used was abstracted from medical records and collected from a follow-up survey for up to one-year post-hospitalization. Hospitalization data included demographics, comorbidities, and in-hospital complications. The survey collected long-COVID symptoms, and information on general health, social isolation, and loneliness. To perform the analysis, we created a graph by projecting the data onto eight principal components (PCs) and running the K-nearest neighbors algorithm. We then used Louvain's algorithm to partition this graph into non-overlapping clusters.

RESULTS: The cluster analysis produced four clusters with distinct health and social connectivity patterns. The first cluster (n = 141) consisted of patients with both long-COVID neurological symptoms (74%) and social isolation/loneliness. The second cluster (n = 137) consisted of healthy patients who were also more socially connected and not lonely. The third cluster (n = 96) contained patients with neurological symptoms who were socially connected but lonely, and the fourth cluster (n = 63) consisted entirely of patients who had traumatic COVID hospitalization, were intubated, suffered symptoms, but were socially connected and experienced recovery.

CONCLUSION: The cluster analysis identified social isolation and loneliness as important features associated with long-COVID symptoms and recovery after hospitalization. It also confirms that social isolation and loneliness, though connected, are not necessarily the same. Physicians need to be aware of how social characteristics relate to long-COVID and patient's ability to cope with the resulting symptoms.}, } @article {pmid39060438, year = {2024}, author = {Schwabenland, M and Hasavci, D and Frase, S and Wolf, K and Deigendesch, N and Buescher, JM and Mertz, KD and Ondruschka, B and Altmeppen, H and Matschke, J and Glatzel, M and Frank, S and Thimme, R and Beck, J and Hosp, JA and Blank, T and Bengsch, B and Prinz, M}, title = {High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains.}, journal = {Acta neuropathologica}, volume = {148}, number = {1}, pages = {11}, pmid = {39060438}, issn = {1432-0533}, mesh = {Humans ; *COVID-19/immunology ; *Immunity, Innate/immunology ; *Brain/immunology/pathology ; Male ; Female ; Middle Aged ; Aged ; Microglia/immunology/pathology ; Adult ; CD8-Positive T-Lymphocytes/immunology ; SARS-CoV-2/immunology ; Cicatrix/immunology/pathology ; Machine Learning ; }, abstract = {The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119[+]P2RY12[+]CD68[+]Iba1[+]HLA-DR[+]CD11c[+]SCAMP2[+] microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8[+] parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.}, } @article {pmid39060203, year = {2024}, author = {Ataullahjan, A and Piche-Renaud, PP and Shahrbabak, EK and Fadaleh, SA and Di Chiara, C and Rodriguez, DA and Peresin, J and Morris, SK}, title = {Weighing the risks and benefits: Parental perspectives on COVID-19 vaccines for 5- to 11-year-old children.}, journal = {Vaccine}, volume = {42}, number = {25}, pages = {126154}, doi = {10.1016/j.vaccine.2024.126154}, pmid = {39060203}, issn = {1873-2518}, mesh = {Humans ; *Parents/psychology ; Child ; *COVID-19/prevention & control/epidemiology ; Child, Preschool ; *COVID-19 Vaccines/adverse effects/administration & dosage ; Female ; Male ; *Vaccination/psychology/adverse effects ; *Focus Groups ; *SARS-CoV-2/immunology ; *Decision Making ; Risk Assessment ; Qualitative Research ; Adult ; Health Knowledge, Attitudes, Practice ; }, abstract = {BACKGROUND: Parents are the primary decision makers for their children's vaccination, yet, we have limited knowledge on what influences their decision making related to COVID-19 vaccination. The study aimed to understand these different considerations that shape the decisions of parents of children aged 5-11 years old.

METHODS: We conducted a qualitative study that included online focus group discussions (FGDs) with parents of children aged 5-11 years old. Data was collected between July 26th, 2022, and February 15th, 2023. A total of eight FGDs were conducted, audio-recorded and transcribed verbatim. Thematic analysis was conducted, and peer debriefing was used to ensure methodological rigor.

RESULTS: Findings revealed that parents of vaccinated and unvaccinated children employed language of risk-benefit analysis to inform their decision-making. Parents of vaccinated children highlighted concerns about spreading COVID-19, family member's health, and long COVID-19. For parents of unvaccinated children, they perceived potential vaccine side effects as more harmful than the risks associated with COVID-19. Participants contended that there was a lack of transparency from the government and public health agencies, highlighting inconsistent messaging which had fractured their trust in COVID-19-related recommendations and mandates.

CONCLUSIONS: Our results indicate that improved transparency on how evidence is developed and why recommendations and mandates shift during the pandemic would foster trust in the government and public health agencies. Open communication with health providers on the potential risks and benefits would also improve caregivers confidence in the vaccine.}, } @article {pmid39059998, year = {2024}, author = {Sherwood, O}, title = {Covid-19 inquiry: We must not ignore the long term health impacts of covid.}, journal = {BMJ (Clinical research ed.)}, volume = {386}, number = {}, pages = {q1679}, doi = {10.1136/bmj.q1679}, pmid = {39059998}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *SARS-CoV-2 ; Pandemics ; }, } @article {pmid39058743, year = {2024}, author = {Foppiani, A and Montanari, C and Zanelli, S and Lombardo, MDM and Calcaterra, V and Zuccotti, G}, title = {Long-COVID symptom monitoring: Insights from a two-year telemedicine study.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0307834}, pmid = {39058743}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/virology/diagnosis ; *Telemedicine ; Female ; Male ; Middle Aged ; *SARS-CoV-2/isolation & purification ; Aged ; Adult ; Follow-Up Studies ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; }, abstract = {BACKGROUND: The diverse manifestations of Long-COVID have become increasingly important due to their significant impact on patients' lives. Telemedicine has emerged as an important tool for post COVID-19 follow-up. This study is part of a large cohort study involving COVID-positive patients monitored by the COD19 telemedicine platform operations center. We recontacted patients who were initially monitored from February 2020 to May 2020 to assess the presence of Long-COVID symptoms at a 2-year follow-up.

METHODS: We conducted interviews to evaluate Long-COVID symptoms at the 2-year mark and investigated whether patients had contracted a second COVID-19 infection between the 1-year and 2-year follow-ups, and recorded their vaccination status.

RESULTS: Out of 165 patients, 139 (84%) reported symptoms at the 1-year follow-up, while only 101 (61%) reported symptoms at the 2-year follow-up. Among patients with Long-COVID symptoms at the 2-year follow-up, the majority (80, 49%) had experienced Long-COVID at the 1-year follow-up, received the SARS-CoV-2 vaccine, and had not experienced a second infection between the two follow-ups. Both having Long-COVID at the 1-year follow-up and contracting a second infection were significant risk factors for presenting with Long-COVID at the 2-year follow-up.

CONCLUSIONS: To the best of our knowledge, this study stands out as one of the few that includes a 2-year follow-up on Long-COVID symptoms using telemedicine. Telemedicine has proven to be an effective and innovative tool for long-term patient monitoring, early diagnosis, and treatment. Telemedicine represents a significant future challenge for healthcare.}, } @article {pmid39057605, year = {2024}, author = {Weng, CT and Wei, KC and Yang, CC}, title = {The Need to Analyze Telogen Effluvium and Alopecia Areata Parallelly in Long COVID Studies.}, journal = {Influenza and other respiratory viruses}, volume = {18}, number = {7}, pages = {e13356}, pmid = {39057605}, issn = {1750-2659}, mesh = {Humans ; *Alopecia Areata/etiology ; *COVID-19/epidemiology/complications ; *SARS-CoV-2 ; Female ; }, } @article {pmid39057586, year = {2024}, author = {Salci, MA and Carreira, L and Oliveira, NN and Pereira, ND and Covre, ER and Pesce, GB and Oliveira, RR and Höring, CF and Baccon, WC and Puente Alcaraz, J and Santos, GA and Bolsoni, LLM and Gutiérrez Carmona, A and Vissoci, JRN and Facchini, LA and Laranjeira, C}, title = {Long COVID among Brazilian Adults and Elders 12 Months after Hospital Discharge: A Population-Based Cohort Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {14}, pages = {}, pmid = {39057586}, issn = {2227-9032}, support = {This work was funded by Ministério da Ciência, Tecnologia, Inovações e Comunicações (FNDCT/MCTIC), Ministério da Saúde (MS) and Conselho Nacional de Desenvolvimento Cientí-ficoTecnológico (CNPq)  Processo n.° 402,882/2020-2. It was supported by FCT-Funda//Fundação para a Ciência e Tecnologia/ ; }, abstract = {The persistence of symptoms for more than three months following infection with severe acute respiratory syndrome coronavirus 2 is referred to as "Long COVID". To gain a deeper understanding of the etiology and long-term progression of symptoms, this study aims to analyze the prevalence of Long COVID and its associated factors in a cohort of Brazilian adults and elders, twelve months after hospital discharge. An observational, prospective, and follow-up study was performed with a cohort of adults and older adults diagnosed with COVID-19 in 2020 in the State of Paraná, Brazil. Twelve months after hospital discharge, patients answered a phone questionnaire about the persistence of symptoms after three levels of exposure to COVID-19's acute phase (ambulatory, medical ward, and intensive care unit). According to the characteristics of participants, the prevalence of Long COVID-19 was calculated, and logistic regression analyses were conducted. We analyzed data from 1822 participants (980 adults [≥18-<60 years] and 842 older people [≥60 years]) across three exposure levels. The overall Long COVID prevalence was 64.2%. Long COVID was observed in 646 adults (55%; of which 326 were women) and 523 older people (45%; of which 284 were women). Females had a higher prevalence of long-term symptoms (52%) compared with men. The most common post-COVID-19 conditions in the 12-month follow-up were neurological (49.8%), followed by musculoskeletal (35.1%) and persistent respiratory symptoms (26.5%). Male individuals were less likely to develop Long COVID (aOR = 0.50). Other determinants were also considered risky, such as the presence of comorbidities (aOR = 1.41). Being an adult and having been hospitalized was associated with the development of Long COVID. The risk of developing Long COVID was twice as high for ward patients (aOR = 2.53) and three times as high for ICU patients (aOR = 3.56) when compared to non-hospitalized patients. Presenting clinical manifestations of digestive (aOR = 1.56), endocrine (aOR = 2.14), cutaneous (aOR = 2.51), musculoskeletal (aOR = 2.76) and psychological systems (aOR = 1.66) made adults more likely to develop Long COVID. Long COVID was present in a large proportion of people affected by the SARS-CoV-2 infection. Presence of Long COVID symptoms displayed a dose-response relationship with the level of disease exposure, with a greater prevalence of symptoms associated with the severe form in the acute period.}, } @article {pmid39056479, year = {2024}, author = {Lasalvia, A and Bodini, L and Pace, D and Colombi, M and Caruson, MM and Van Bortel, T and Bonetto, C}, title = {Experienced discrimination and internalized stigma among people infected with SARS-CoV-2 and surviving COVID-19: Association with anxiety, depression, and insomnia symptoms.}, journal = {Journal of community psychology}, volume = {52}, number = {7}, pages = {910-928}, doi = {10.1002/jcop.23136}, pmid = {39056479}, issn = {1520-6629}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Male ; *Social Stigma ; *Sleep Initiation and Maintenance Disorders/psychology/epidemiology ; Adult ; Middle Aged ; *Depression/psychology ; *Anxiety/psychology ; *SARS-CoV-2 ; Surveys and Questionnaires ; Aged ; Young Adult ; Social Discrimination/psychology ; }, abstract = {People surviving COVID-19 may experience social stigma related to their condition even after clinical recovery. This study aimed to: (1) investigate COVID-19-related experienced discrimination and internalized stigma, and (2) explore their association with symptoms of anxiety, depression, and insomnia. We conducted an online survey of people who survived COVID-19. Perception of stigma was assessed using the COVID-19 Experienced Discrimination Scale and the COVID-19 Internalized Stigma Scale. Depression, anxiety, and insomnia were assessed using, respectively, the Patient Health Questionnaire-9, the General Anxiety Disorder Scale-7, and the Insomnia Severity Index. Multivariable logistic regression analyses for each psychopathological domain were performed. A total of 579 participants participated in this study. Overall, 25% reported some degree of experienced discrimination, and 23% reported some degree of internalized stigma. Adjusted odds ratio showed that scoring higher on internalized stigma related significantly to higher symptoms of depression (2.14; 95% confidence interval [CI], 1.35-3.39), anxiety (2.30; 95% CI, 1.48-3.59), and insomnia (2.54; 95% CI, 1.64-3.95), whereas experienced discrimination was associated to anxiety (1.55; 95% CI, 1.06-2.28) and insomnia (1.82; 95% CI, 1.24-2.69). Experiences of social stigmatization are frequent among people surviving COVID-19 and seem to be associated with levels of psychological disturbances. Further research is required to elucidate the direction of these relationships to implement effective treatment strategies.}, } @article {pmid39056206, year = {2024}, author = {Jiang, X and Gao, X and Ding, J and Pang, B and Pei, Y and Zhao, Z and Zhao, N and Wang, Z and Chen, C and Gao, D and Yan, F and Wang, F and Liu, C and Zhang, Z and Li, Z and Zhao, Z}, title = {Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29812}, doi = {10.1002/jmv.29812}, pmid = {39056206}, issn = {1096-9071}, support = {//Construction Funds of Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment from The First Hospital of Hebei Medical University; and other Hebei Province Projects/ ; //National Natural Science Foundation of China/ ; //The Natural Science Foundation of Hebei/ ; //Hebei Provincial Department of Human Resources and Social Security/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *COVID-19/therapy/complications ; *Diarrhea/therapy/microbiology/virology ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Depression/therapy ; Prospective Studies ; Adult ; Aged ; Feces/microbiology/virology ; SARS-CoV-2 ; Treatment Outcome ; Aspartate Aminotransferases/blood ; Gastrointestinal Microbiome ; }, abstract = {Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.}, } @article {pmid39056070, year = {2024}, author = {Zhang, Y and Ba, DM and Risher, K and Liao, D and Parent, LJ and Ghahramani, N and Chinchilli, VM}, title = {Effects of ACE inhibitor/ARB therapy and long COVID on kidney disease: a retrospective cohort study using real-world data.}, journal = {Clinical kidney journal}, volume = {17}, number = {7}, pages = {sfae164}, pmid = {39056070}, issn = {2048-8505}, abstract = {BACKGROUND: The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID.

METHODS: A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers.

RESULTS: Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings.

CONCLUSIONS: ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.}, } @article {pmid39055942, year = {2024}, author = {Wang, J and Liang, X and Zheng, Y and Zhu, Y and Zhou, K and Wu, X and Sun, R and Hu, Y and Zhu, X and Chi, H and Chen, S and Lyu, M and Xie, Y and Yi, X and Liu, W and Cai, X and Li, S and Zhang, Q and Wu, C and Shi, Y and Wang, D and Peng, M and Zhang, Y and Liu, H and Zhang, C and Quan, S and Kong, Z and Kang, Z and Zhu, G and Zhu, H and Chen, S and Liang, J and Yang, H and Pang, J and Fang, Y and Chen, H and Li, J and Xu, J and Guo, T and Shen, B}, title = {Pulmonary and renal long COVID at two-year revisit.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110344}, pmid = {39055942}, issn = {2589-0042}, abstract = {This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.}, } @article {pmid39055310, year = {2024}, author = {Garg, M and Prabhakar, N and Devkota, S and Dhooria, S and Debi, U and Dua, A and Singh, T and Malarakunte, M and Bhatia, H and Sandhu, MS}, title = {Chest CT Findings at Six Months Following COVID-19 ARDS - Correlation With the mMRC Dyspnea Scale and Pulmonary Function Tests.}, journal = {British journal of biomedical science}, volume = {81}, number = {}, pages = {12871}, pmid = {39055310}, issn = {2474-0896}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; Male ; Female ; *Dyspnea/diagnostic imaging/physiopathology ; Middle Aged ; *Respiratory Function Tests ; Prospective Studies ; *Tomography, X-Ray Computed/methods ; Lung/diagnostic imaging/physiopathology ; SARS-CoV-2 ; Aged ; Respiratory Distress Syndrome/diagnostic imaging/physiopathology ; Adult ; Severity of Illness Index ; Vital Capacity ; }, abstract = {Background: Many survivors of severe COVID-19 pneumonia experience lingering respiratory issues. There is limited research on follow-up chest imaging findings in patients with COVID-19 ARDS, particularly in relation to their mMRC dyspnea scores and pulmonary function tests (PFTs). This study addresses this gap by investigating the clinical characteristics, mMRC dyspnea scores, PFTs, and chest CT findings of COVID-19 ARDS patients at the 6 months post-recovery. By analyzing these variables together, we aim to gain a better understanding of the long-term health consequences of COVID-19 ARDS. Methods: This prospective observational study included 56 subjects with COVID-19 ARDS with dyspnea at the six-month follow-up visits. These patients were evaluated by chest CT, mMRC dyspnea scale, and PFT. The CT severity score was calculated individually for each of the four major imaging findings - ground glass opacities (GGOs), parenchymal/atelectatic bands, reticulations/septal thickening, and consolidation - using a modified CT severity scoring system. Statistics were carried out to find any association between individual CT chest findings and the mMRC dyspnea scale and forced vital capacity (FVC). p values < 0.05 were considered statistically significant. Results: Our study population had a mean age of 55.86 ± 9.60 years, with 44 (78.6%) being men. Grades 1, 2, 3, and 4 on the mMRC dyspnea scale were seen in 57.1%, 30.4%, 10.7%, and 1.8% of patients respectively. Common CT findings observed were GGOs (94.6%), reticulations/septal thickening (96.4%), parenchymal/atelectatic bands (92.8%), and consolidation (14.3%). The mean modified CT severity scores for GGOs, reticulations/septal thickening, parenchymal/atelectatic bands, and consolidation were 10.32 ± 5.51 (range: 0-21), 7.66 ± 4.33 (range: 0-19), 4.77 ± 3.03 (range: 0-14) and 0.29 ± 0.91 (range 0-5) respectively. Reticulations/septal thickening (p = 0.0129) and parenchymal/atelectatic bands (p = 0.0453) were associated with an increased mMRC dyspnea scale. Parenchymal/atelectatic bands were also associated with abnormal FVC (<80%) (p = 0.0233). Conclusion: Six-month follow-up chest CTs of COVID-19 ARDS survivors with persistent respiratory problems showed a statistically significant relationship between increased mMRC dyspnea score and imaging patterns of reticulations/septal thickening and parenchymal/atelectatic bands; while parenchymal/atelectatic bands also showed a statistically significant correlation with reduced FVC.}, } @article {pmid39053954, year = {2024}, author = {Lewandowska, K and Lipski, D and Uruski, P and Narkiewicz, K and Januszewicz, A and Wolf, J and Prejbisz, A and Rajzer, M and Więcek, A and Tykarski, A}, title = {Randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome: the ALL-VASCOR study protocol.}, journal = {BMJ open}, volume = {14}, number = {7}, pages = {e075741}, pmid = {39053954}, issn = {2044-6055}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Allopurinol/therapeutic use ; *Cardiovascular Diseases/prevention & control ; *COVID-19/complications ; Double-Blind Method ; Heart Disease Risk Factors ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality.

METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland.

ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences.

PROTOCOL VERSION NUMBER: 01-15 November 2022.

TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.}, } @article {pmid39053941, year = {2024}, author = {Zapata, T and Gosling, J and McFarland, S}, title = {We can do better for young people with long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {386}, number = {}, pages = {q1664}, doi = {10.1136/bmj.q1664}, pmid = {39053941}, issn = {1756-1833}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Adolescent ; *SARS-CoV-2 ; Young Adult ; Post-Acute COVID-19 Syndrome ; United Kingdom/epidemiology ; }, } @article {pmid39052056, year = {2024}, author = {Gutzeit, J and Weiß, M and Nürnberger, C and Lemhöfer, C and Appel, KS and Pracht, E and Reese, JP and Lehmann, C and Polidori, MC and Hein, G and Deckert, J}, title = {Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {39052056}, issn = {1433-8491}, abstract = {Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.}, } @article {pmid39051280, year = {2024}, author = {Centorbi, M and Di Martino, G and Della Valle, C and Iuliano, E and Di Claudio, G and Mascioli, A and Calcagno, G and di Cagno, A and Buonsenso, A and Fiorilli, G}, title = {Regular Physical Activity Can Counteract LONG COVID Symptoms in Adults over 40.}, journal = {Journal of functional morphology and kinesiology}, volume = {9}, number = {3}, pages = {}, pmid = {39051280}, issn = {2411-5142}, abstract = {UNLABELLED: Three years after the SARS-CoV-19 pandemic, a chronic post-COVID syndrome "LONG COVID" persists, causing fatigue and shortness of breath, along with distress, anxiety, and depression.

AIM: To assess the impact of physical activity on the management and rehabilitation of LONG COVID, as well as to investigate the persistence of LONG COVID symptomatology in individuals over 40 years, beyond the pandemic.

METHODS: A total of 1004 participants (aged 53.45 ± 11.35) were recruited through an online snowball sampling strategy to complete a web-based survey. The following questionnaires were administered: Physical Activity Scale for Elderly (PASE), Shortness of Breath Questionnaire (SOBQ), Patient Health Questionnaire-9 item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), and Fatigue Scale for Motor and Cognitive Functions (FSMC).

RESULTS: Significant gender differences were discovered, with women reporting higher symptoms than men (p < 0.001). Significant age differences were also found, with participants under 55 showing higher values than those over 55 (p < 0.001). No significant differences were found between aerobic and mixed physical activity (p > 0.05) while significant results emerged between physical activity groups and the no activity group (p < 0.001). The low-frequency group reported higher symptoms than the high-frequency group (all ps < 0.001).

CONCLUSION: Regardless of the type of physical activity performed, our survey identified the frequency of training as a crucial factor to overcome LONG COVID symptoms; the challenge lies in overcoming the difficulties due to the persistent feelings of inefficiency and fatigue typical of those who have contracted the infection.}, } @article {pmid39051242, year = {2024}, author = {Sideratou, CM and Papaneophytou, C}, title = {Persistent Vascular Complications in Long COVID: The Role of ACE2 Deactivation, Microclots, and Uniform Fibrosis.}, journal = {Infectious disease reports}, volume = {16}, number = {4}, pages = {561-571}, pmid = {39051242}, issn = {2036-7430}, abstract = {Angiotensin-converting enzyme 2 (ACE2), a key regulator in vasoregulation and the renin-angiotensin system, is hypothesized to be downregulated in patients with COVID-19, leading to a cascade of cardiovascular complications. This deactivation potentially results in increased blood pressure and vessel injury, contributing to the formation and persistence of microclots in the circulation. Herein, we propose a hypothesis regarding the prolonged vascular complications observed in long COVID, focusing on the role of ACE2 deactivation and/or shedding, the persistence of microclots, and the unique pattern of fibrosis induced by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Furthermore, we propose that the distinctive, uniform fibrosis associated with COVID-19, which is challenging to detect through conventional X-ray imaging, exacerbates vascular injury and impairs oxygenation. The persistence of these microclots and the unique fibrosis pattern are suggested as key factors in the extended duration of vascular complications post-COVID-19 infection, regardless of the initial disease severity. Moreover, plasma ACE2 activity has the potential to serve as prognostic or diagnostic biomarkers for monitoring disease severity and managing long COVID symptoms. Elucidating the role of ACE2 deactivation and the consequent events is vital for understanding the long-term effects of COVID-19. The experimental verification of this hypothesis through in vitro studies, clinical longitudinal studies, and advanced imaging techniques could yield significant insights into the pathophysiological mechanisms underlying long COVID, thereby improving the management of patients, particularly those with cardiovascular complications.}, } @article {pmid39049529, year = {2024}, author = {O'Brien, KK and McDuff, K and Chattu, VK and Churchill, K and Colantonio, A and Davenport, TE and Gross, DP and Jaglal, S and Kho, M and Leighton, J and Premnazeer, M and Rendely, A and Scali, O and Skoretz, S and Wasilewski, M and Cameron, JI}, title = {A framework of research priorities in COVID rehabilitation from the Rehabilitation Science Research Network for COVID: an international consultation involving qualitative and quantitative research.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/09638288.2024.2382904}, pmid = {39049529}, issn = {1464-5165}, abstract = {PURPOSE: To identify research priorities related to COVID rehabilitation from the perspectives of persons with lived experiences, clinicians, researchers, community organization and policy representatives.

MATERIALS & METHODS: We conducted five international consultations to identify key issues and research priorities in COVID rehabilitation using (i) web-based questionnaires, (ii) synchronous discussions, and (iii) content analysis of COVID rehabilitation research conference presentations. We collated responses and notes and then analyzed data using content analytical techniques.

RESULTS: The Framework of Research Priorities in COVID Rehabilitation includes five priorities that span health and disability across COVID-19 and Long COVID illness trajectories: (1) understanding experiences of episodic disability; (2) assessing episodic disability; (3) identifying and examining safe approaches to rehabilitation; (4) examining the role, implementation, and impact of models of rehabilitation care; and (5) examining access to safe, timely and appropriate rehabilitation and other health care provider services. The Framework identifies target populations, methodological considerations, and highlights the importance of integrated knowledge translation and exchange in advancing scientific evidence, clinical education, practice, and COVID rehabilitation policy.

CONCLUSIONS: This Framework provides a foundation to advance COVID, disability and rehabilitation research to advance the health and well-being of persons with COVID-19, Long COVID, and their caregivers.Implications for rehabilitationPersons with COVID-19 or Long COVID and their caregivers may experience multi-dimensional forms of disability spanning physical, cognitive, emotional health challenges, difficulties with daily function, and social inclusion, which individually and/or collectively may be unpredictable, episodic and/or chronic in nature.Rehabilitation has a role in preventing or mitigating disability and enhancing health outcomes for persons with COVID-19, Long COVID and their caregivers.The Framework of Research Priorities COVID Rehabilitation includes five overlapping research priorities spanning health and disability across COVID trajectories: (1) understanding experiences of episodic disability; (2) assessing episodic disability; (3) identifying and examining safe approaches to rehabilitation; (4) examining the role, implementation, and impact of models of rehabilitation care; and (5) examining access to safe, timely and appropriate rehabilitation and other health care provider services.The research priorities in the Framework represent a comprehensive approach to examine disability and rehabilitation across COVID illness trajectories and the broad continuums of rehabilitation care to provide a coordinated and collaborative approach to advancing evidence in COVID disability and rehabilitation.This Framework provides a foundation for international and interdisciplinary collaborations, to advance COVID disability and rehabilitation research to enhance health outcomes of persons with COVID-19, Long COVID, and their caregivers.}, } @article {pmid39048833, year = {2024}, author = {Schild, AK and Scharfenberg, D and Regorius, A and Klein, K and Kirchner, L and Yasemin, G and Lülling, J and Meiberth, D and Schweitzer, F and Fink, GR and Jessen, F and Franke, C and Onur, OA and Jost, ST and Warnke, C and Maier, F}, title = {Six-month follow-up of multidomain cognitive impairment in non-hospitalized individuals with post-COVID-19 syndrome.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1945-1957}, pmid = {39048833}, issn = {1433-8491}, mesh = {Humans ; Male ; Female ; *Cognitive Dysfunction/etiology/physiopathology ; *COVID-19/complications ; Middle Aged ; Follow-Up Studies ; *Neuropsychological Tests ; *Post-Acute COVID-19 Syndrome ; Aged ; Adult ; Quality of Life ; }, abstract = {Some people infected with SARS-CoV-2 report persisting symptoms following acute infection. If these persist for over three months, they are classified as post-COVID-19 syndrome (PCS). Although PCS is frequently reported, detailed longitudinal neuropsychological characterization remains scarce. We aimed to describe the trajectory of cognitive and neuropsychiatric PCS symptoms. 42 individuals with persisting cognitive deficits after asymptomatic to mild/moderate acute COVID-19 at study inclusion received neuropsychological assessment at baseline (BL) and follow-up (FU; six months after BL). Assessments included comprehensive testing of five neurocognitive domains, two cognitive screening tests, and questionnaires on depression, anxiety, sleep, fatigue, and health-related quality of life. Results showed high rates of subjective cognitive complaints at BL and FU (95.2% versus 88.1%) without significant change over time. However, objectively measured neurocognitive disorder (NCD) decreased (61.9% versus 42.9%). All cognitive domains were affected, yet most deficits were found in learning and memory, followed by executive functions, complex attention, language, and perceptual motor functions. In individuals with NCD, the first three domains mentioned improved significantly over time, while the last two domains remained unchanged. Cognitive screening tests did not prove valuable in detecting impairment. Neuropsychiatric symptoms remained constant except for quality of life, which improved. This study emphasizes the importance of comprehensive neuropsychological assessment in longitudinal research and provides valuable insights into the trajectory of long-term neuropsychological impairments in PCS. While cognitive performance significantly improved in many domains, neuropsychiatric symptoms remained unchanged.}, } @article {pmid39047785, year = {2024}, author = {Gandjour, A}, title = {Evaluating the Usefulness of Population-Wide COVID-19 Testing in the Omicron Era: Insights from a German Model.}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {86}, number = {12}, pages = {776-782}, pmid = {39047785}, issn = {1439-4421}, mesh = {*COVID-19/epidemiology/transmission/prevention & control/diagnosis ; Germany/epidemiology ; Humans ; *SARS-CoV-2 ; *COVID-19 Testing/statistics & numerical data ; Mass Screening/statistics & numerical data ; Pandemics/prevention & control ; Incidence ; Adult ; Middle Aged ; Seasons ; Aged ; }, abstract = {BACKGROUND: The Omicron variant of SARS-CoV-2, which has become dominant worldwide since late 2021, presents a unique challenge due to its high rate of asymptomatic transmission. This study evaluates the efficacy and value of population-wide testing, including self-testing, in the context of COVID-19, particularly under the Omicron variant, using data from Germany.

METHODS: A decision-analytical model and secondary data was used for assessing the impact of systematic screening and testing for COVID-19. Various scenarios were taken into consideration including seasonal patterns of COVID-19 transmission and the potential for annual waves. The model assessed the clinical benefits of testing against the backdrop of vaccine effectiveness, transmission rates, and the potential to prevent severe clinical events, including death, ICU admission, and long COVID syndrome.

RESULTS: The study found that the value of mass testing and self-testing for private use was highly contingent on the transmission rate and the scenario of COVID-19 waves (seasonal vs. continuous). For winter waves, a very high incidence rate was required to justify testing, while for continuous waves, testing could be valuable for those in contact with individuals in their last decade of life. The analysis highlighted the limitations of mass testing when community transmission rates were low and the potential value of testing in high-risk contacts or amidst new outbreaks.

CONCLUSION: The findings suggest that the resumption of testing during winter waves is unlikely to provide significant clinical benefits given the current understanding of Omicron's transmission and immunity waning. This study underscores the need for a nuanced approach to COVID-19 testing policies, considering both the epidemiological context and the practical implications of testing strategies.}, } @article {pmid39045815, year = {2024}, author = {Wu, PF and Summers, C and Panesar, A and Kaura, A and Zhang, L}, title = {AI Hesitancy and Acceptability-Perceptions of AI Chatbots for Chronic Health Management and Long COVID Support: Survey Study.}, journal = {JMIR human factors}, volume = {11}, number = {}, pages = {e51086}, pmid = {39045815}, issn = {2292-9495}, mesh = {Humans ; *Artificial Intelligence ; *COVID-19/psychology/epidemiology ; Middle Aged ; Chronic Disease/therapy/psychology ; Male ; Female ; Surveys and Questionnaires ; Aged ; Adult ; Self-Management/psychology/methods ; }, abstract = {BACKGROUND: Artificial intelligence (AI) chatbots have the potential to assist individuals with chronic health conditions by providing tailored information, monitoring symptoms, and offering mental health support. Despite their potential benefits, research on public attitudes toward health care chatbots is still limited. To effectively support individuals with long-term health conditions like long COVID (or post-COVID-19 condition), it is crucial to understand their perspectives and preferences regarding the use of AI chatbots.

OBJECTIVE: This study has two main objectives: (1) provide insights into AI chatbot acceptance among people with chronic health conditions, particularly adults older than 55 years and (2) explore the perceptions of using AI chatbots for health self-management and long COVID support.

METHODS: A web-based survey study was conducted between January and March 2023, specifically targeting individuals with diabetes and other chronic conditions. This particular population was chosen due to their potential awareness and ability to self-manage their condition. The survey aimed to capture data at multiple intervals, taking into consideration the public launch of ChatGPT, which could have potentially impacted public opinions during the project timeline. The survey received 1310 clicks and garnered 900 responses, resulting in a total of 888 usable data points.

RESULTS: Although past experience with chatbots (P<.001, 95% CI .110-.302) and online information seeking (P<.001, 95% CI .039-.084) are strong indicators of respondents' future adoption of health chatbots, they are in general skeptical or unsure about the use of AI chatbots for health care purposes. Less than one-third of the respondents (n=203, 30.1%) indicated that they were likely to use a health chatbot in the next 12 months if available. Most were uncertain about a chatbot's capability to provide accurate medical advice. However, people seemed more receptive to using voice-based chatbots for mental well-being, health data collection, and analysis. Half of the respondents with long COVID showed interest in using emotionally intelligent chatbots.

CONCLUSIONS: AI hesitancy is not uniform across all health domains and user groups. Despite persistent AI hesitancy, there are promising opportunities for chatbots to offer support for chronic conditions in areas of lifestyle enhancement and mental well-being, potentially through voice-based user interfaces.}, } @article {pmid39044822, year = {2024}, author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A}, title = {Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1422940}, pmid = {39044822}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects/immunology ; *Fatigue Syndrome, Chronic/immunology/etiology/virology ; HLA-DRB1 Chains/genetics/immunology ; *Post-Acute COVID-19 Syndrome/immunology ; }, abstract = {Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.}, } @article {pmid39043760, year = {2024}, author = {Kato, A and Tokumasu, K and Yamamoto, K and Otsuka, Y and Nakano, Y and Honda, H and Sunada, N and Sakurada, Y and Matsuda, Y and Hasegawa, T and Takase, R and Ueda, K and Otsuka, F}, title = {Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {17025}, pmid = {39043760}, issn = {2045-2322}, support = {22fk0108517h0001//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology/blood ; *Orthostatic Intolerance/physiopathology/blood ; Male ; Female ; Middle Aged ; Adult ; *Heart Rate ; Aged ; *Blood Pressure ; SARS-CoV-2/isolation & purification ; Hydrocortisone/blood ; Post-Acute COVID-19 Syndrome ; Young Adult ; }, abstract = {Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.}, } @article {pmid39043712, year = {2024}, author = {Caohuy, H and Eidelman, O and Chen, T and Mungunsukh, O and Yang, Q and Walton, NI and Pollard, BS and Khanal, S and Hentschel, S and Florez, C and Herbert, AS and Pollard, HB}, title = {Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16895}, pmid = {39043712}, issn = {2045-2322}, support = {HU00012120068//U.S. Department of Defense (United States Department of Defense)/ ; HU00011920047//U.S. Department of Defense (United States Department of Defense)/ ; R01 HL167048/HL/NHLBI NIH HHS/United States ; IAA-AA-HL-14-007//U.S. Department of Health and Human Services | National Institutes of Health (NIH)/ ; 1RO1HL167048//U.S. Department of Health and Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)/ ; 1RO1HL167048//U.S. Department of Health and Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *Signal Transduction ; *COVID-19/metabolism/virology ; *SARS-CoV-2/physiology ; *Inflammation/metabolism ; NF-kappa B/metabolism ; Epithelial Sodium Channels/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Ouabain/pharmacology ; }, abstract = {SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper-proinflammatory immune response in the host airway. This hyper-proinflammatory state involves activation of signaling by NFκB, and unexpectedly, ENaC, the epithelial sodium channel. Post-infection inflammation may also contribute to "Long COVID"/PASC. Enhanced signaling by NFκB and ENaC also marks the airway of patients suffering from cystic fibrosis, a life-limiting proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 spike protein, and therefore activation of both NFκB and ENaC signaling. We used western blot and electrophysiological techniques, and an organoid model of normal airway epithelia, differentiated on an air-liquid-interface (ALI). We found that CFTR protein expression and CFTR cAMP-activated chloride channel activity were lost when the model epithelium was exposed to SARS-CoV-2 spike proteins. As hypothesized, the absence of CFTR led to activation of both TNFα/NFκB signaling and α and γ ENaC. We had previously shown that the cardiac glycoside drugs digoxin, digitoxin and ouabain blocked interaction of spike protein and ACE2. Consistently, addition of 30 nM concentrations of the cardiac glycoside drugs, prevented loss of both CFTR protein and CFTR channel activity. ACE2 and CFTR were found to co-immunoprecipitate in both basal cells and differentiated epithelia. Thus spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane. Thus, failure of CFTR recovery from endosomal recycling might be a mechanism for spike-dependent loss of CFTR. Finally, we found that authentic SARS-CoV-2 virus infection induced loss of CFTR protein, which was rescued by the cardiac glycoside drugs digitoxin and ouabain. Based on experiments with this organoid model of small airway epithelia, and comparisons with 16HBE14o- and other cell types expressing normal CFTR, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by the SARS-CoV-2 spike protein, thus inducing a cystic fibrosis-like clinical phenotype. To our knowledge this is the first time COVID-19 airway inflammation has been experimentally traced in normal subjects to a contribution from SARS-CoV-2 spike-dependent inhibition of CFTR signaling.}, } @article {pmid39043345, year = {2024}, author = {Frank, MG and Ball, JB and Hopkins, S and Kelley, T and Kuzma, AJ and Thompson, RS and Fleshner, M and Maier, SF}, title = {SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids.}, journal = {Brain, behavior, and immunity}, volume = {121}, number = {}, pages = {87-103}, doi = {10.1016/j.bbi.2024.07.034}, pmid = {39043345}, issn = {1090-2139}, mesh = {Animals ; Rats ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; Male ; *Neuroinflammatory Diseases/immunology ; *Lipopolysaccharides/pharmacology ; *Spike Glycoprotein, Coronavirus/immunology/metabolism ; Brain/immunology/metabolism/drug effects ; Adrenal Cortex Hormones/pharmacology ; Rats, Sprague-Dawley ; Inflammation/immunology/metabolism ; }, abstract = {Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 antigens (e.g., spike S1 subunit) are found in the circulation of Long COVID patients, have been detected in post-mortem brain of COVID patients, and exhibit neuroinflammatory properties. Considering recent observations of chronic neuroinflammation in Long COVID patients, the present study explores the idea that antigens derived from SARS-CoV-2 might produce a long-term priming or sensitization of neuroinflammatory processes, thereby potentiating the magnitude and/or duration of the neuroinflammatory response to future inflammatory insults. Rats were administered S1 or vehicle intra-cisterna magna and 7d later challenged with vehicle or LPS. The neuroinflammatory, physiological, and behavioral responses to LPS were measured at various time points post-LPS. We found that prior S1 treatment potentiated many of these responses to LPS suggesting that S1 produces a protracted priming of these processes. Further, S1 produced a protracted reduction in basal brain corticosteroids. Considering the anti-inflammatory properties of corticosteroids, these findings suggest that S1 might disinhibit innate immune processes in brain by reducing anti-inflammatory drive, thereby priming neuroinflammatory processes. Given that hypocortisolism is observed in Long COVID, we propose that similar S1-induced innate immune priming processes might play role in the pathophysiology of Long COVID.}, } @article {pmid39042286, year = {2024}, author = {Maiti, AK}, title = {Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome.}, journal = {Immunogenetics}, volume = {76}, number = {5-6}, pages = {279-290}, pmid = {39042286}, issn = {1432-1211}, mesh = {Humans ; Black or African American/genetics ; *Computational Biology/methods ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Hispanic or Latino/genetics ; *Polymorphism, Single Nucleotide ; *Post-Acute COVID-19 Syndrome/genetics ; }, abstract = {Long or Post COVID-19 is a condition of collected symptoms persisted after recovery from COVID-19. Host genetic factors play a crucial role in developing Long COVID-19, and GWAS studies identified several SNPs/genes in various ethnic populations. In African-American population two SNPS, rs10999901 (C>T, p = 3.6E-08, OR = 1.39, MAF-0,27, GRCH38, chr10:71584799 bp) and rs1868001 (G>A, p = 6.7E-09, OR = 1.40, MAF-0.46, GRCH38, chr10:71587815 bp) and in Hispanic population, rs3759084 (A>C, p = 9.7E-09, OR = 1.56, MAF-0.17, chr12: 81,110,156 bp) are strongly associated with Long COVID-19. All these three SNPs reside in noncoding regions implying their regulatory function in the genome. In silico dissection suggests that rs10999901 and rs1868001 physically interact with the CDH23 and C10orf105 genes. Both SNPs act as distant enhancers and bind with several transcription factors (TFs). Further, rs10999901 SNP is a CpG that is methylated in CD4++ T cells and monocytes and loses its methylation due to transition from C>T. rs3759084 is located in the promoter (- 687 bp) of MYF5, acts as a distant enhancer, and physically interacts with PTPRQ. These results offer plausible explanations for their association and provide the basis for experiments to dissect the development of symptoms of Long COVID-19.}, } @article {pmid39040593, year = {2024}, author = {Daynes, E and Baldwin, MM and Annals, M and Gardiner, N and Chaplin, E and Ward, S and Greening, NJ and Evans, RA and Singh, SJ}, title = {Changes in fatigue symptoms following an exercise-based rehabilitation programme for patients with long COVID.}, journal = {ERJ open research}, volume = {10}, number = {4}, pages = {}, pmid = {39040593}, issn = {2312-0541}, abstract = {BACKGROUND: There is evidence to support COVID-19 rehabilitation programmes improving persistent COVID-19 symptoms; however, there is concern that therapies that include an exercise component may increase fatigue and post-exertional symptom exacerbation (PESE). The objectives of the present study were to determine the effect of a 6-week COVID-19 rehabilitation programme on fatigue and PESE in individuals with ongoing COVID-19 symptoms.

METHODS: After a routine medical assessment, individuals with persistent COVID-19 symptoms were enrolled on a 6-week COVID-19 specific rehabilitation programme. The programme included symptom-titrated exercise, education and self-management advice. Fatigue was assessed pre- and post-programme using the Functional Assessment Chronic Illness Therapy Fatigue questionnaire (FACIT). Exercise capacity (Incremental and Endurance Shuttle Walking Test (ISWT and ESWT)) and PESE (DePaul Symptom Questionnaire (DSQ)) were also assessed pre- and post-programme. Composite scores were calculated for the frequency and severity domains of the DSQ.

RESULTS: 148 patients (median (IQR) age 59 (49-72) years, 82 (55%) female, 81 (54%) hospitalised) completed the COVID-19 rehabilitation programme. FACIT score was reduced pre- to post-programme by a mean (CI) change of -5 (-7- -4); p<0.01. Exercise capacity increased by 82 (65-99) m for the ISWT and 398 (333-462) s for the ESWT (n=148). PESE was assessed in 44 patients. The DSQ frequency and severity composite score improved by 20 (13-28) and 19 (13-26) points, respectively (p<0.01, n=44).

CONCLUSION: These data demonstrate the potential benefits of a COVID-19 rehabilitation programme in improving fatigue, exercise capacity and symptom exacerbation in those with persistent COVID-19 symptoms.}, } @article {pmid39040197, year = {2024}, author = {Uswatte, G and Taub, E and Ball, K and Mitchell, BS and Blake, JA and McKay, S and Biney, F and Iosipchuk, O and Hempfling, P and Harris, E and Dickerson, A and Lokken, K and Knight, AJ and Mark, VW and Agnihotri, S and Cutter, G}, title = {Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39040197}, support = {R01 AG070049/AG/NIA NIH HHS/United States ; }, abstract = {PURPOSE: Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study's objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

DESIGN: Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

RESULTS: Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p<.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048.

CONCLUSIONS: CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.}, } @article {pmid39040190, year = {2024}, author = {Menkir, TF and Citarella, BW and Sigfrid, L and Doshi, Y and Reyes, LF and Calvache, JA and Kildal, AB and Nygaard, AB and Holter, JC and Panda, PK and Jassat, W and Merson, L and Donnelly, CA and Santillana, M and Buckee, C and Verguet, S and Hejazi, NS and , }, title = {Modeling the relative influence of socio-demographic variables on post-acute COVID-19 quality of life.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39040190}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 GM130668/GM/NIGMS NIH HHS/United States ; T32 AI007535/AI/NIAID NIH HHS/United States ; }, abstract = {IMPORTANCE: Post-acute sequelae of SARS-CoV-2, referred to as "long COVID", are a globally pervasive threat. While their many clinical determinants are commonly considered, their plausible social correlates are often overlooked.

OBJECTIVE: To compare social and clinical predictors of differences in quality of life (QoL) with long COVID. Additionally, to measure how much adjusted associations between social factors and long COVID-associated quality of life are unexplained by important clinical intermediates.

Data from the ISARIC long COVID multi-country prospective cohort study. Subjects from Norway, the United Kingdom (UK), and Russia, aged 16 and above, with confirmed acute SARS-CoV-2 infection reporting >= 1 long COVID-associated symptoms 1+ month following infection.

EXPOSURE: The social exposures considered were educational attainment (Norway), employment status (UK and Russia), and female vs male sex (all countries).

MAIN OUTCOME AND MEASURES: Quality of life-adjusted days, or QALDs, with long COVID.

RESULTS: This cohort study included a total of 3891 participants. In all three countries, educational attainment, employment status, and female sex were important predictors of long COVID QALDs. Furthermore, a majority of the estimated relationships between each of these social correlates and long COVID QALDs could not be attributed to key long COVID-predicting comorbidities. In Norway, 90% (95% CI: 77%, 100%) of the adjusted association between the top two quintiles of educational attainment and long COVID QALDs was not explained by clinical intermediates. The same was true for 86% (73%, 100%) and 93% (80%,100%) of the adjusted associations between full-time employment and long COVID QALDs in the United Kingdom (UK) and Russia. Additionally, 77% (46%,100%) and 73% (52%, 94%) of the adjusted associations between female sex and long COVID QALDs in Norway and the UK were unexplained by the clinical mediators.

CONCLUSIONS AND RELEVANCE: This study highlights the role of socio-economic status indicators and female sex, in line with or beyond commonly cited clinical conditions, as predictors of long COVID-associated QoL, and further reveal that other (non-clinical) mechanisms likely drive their observed relationships. Our findings point to the importance of COVID interventions which go further than an exclusive focus on comorbidity management in order to help redress inequalities in experiences with this chronic disease.}, } @article {pmid39039531, year = {2024}, author = {Laestadius, LI and Guidry, JPD and Wahl, MM and Perrin, PB and Carlyle, KE and Dong, X and Gharbo, R and Campos-Castillo, C}, title = {Correction: "The dream is that there's one place you go": a qualitative study of women's experiences seeking care from Long COVID clinics in the USA.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {305}, pmid = {39039531}, issn = {1741-7015}, } @article {pmid39039269, year = {2024}, author = {Prasanth, MI and Wannigama, DL and Reiersen, AM and Thitilertdecha, P and Prasansuklab, A and Tencomnao, T and Brimson, S and Brimson, JM}, title = {Author Correction: A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16774}, doi = {10.1038/s41598-024-67936-4}, pmid = {39039269}, issn = {2045-2322}, } @article {pmid39038980, year = {2024}, author = {Velásquez, EE and Kamdar, NS and Rehkopf, DH and Saydah, S and Bull-Otterson, L and Hao, S and Vala, A and Chu, I and Bazemore, AW and Phillips, RL and Boehmer, T}, title = {Post-COVID Conditions in US Primary Care: A PRIME Registry Comparison of Patients With COVID-19, Influenza-Like Illness, and Wellness Visits.}, journal = {Annals of family medicine}, volume = {22}, number = {4}, pages = {279-287}, pmid = {39038980}, issn = {1544-1717}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; *Registries ; Female ; United States/epidemiology ; *Primary Health Care/statistics & numerical data ; Middle Aged ; *Influenza, Human/epidemiology ; Adult ; *SARS-CoV-2 ; Aged ; Prevalence ; Chronic Disease/epidemiology ; }, abstract = {PURPOSE: COVID-19 is a condition that can lead to other chronic conditions. These conditions are frequently diagnosed in the primary care setting. We used a novel primary care registry to quantify the burden of post-COVID conditions among adult patients with a COVID-19 diagnosis across the United States.

METHODS: We used the American Family Cohort, a national primary care registry, to identify study patients. After propensity score matching, we assessed the prevalence of 17 condition categories individually and cumulatively, comparing patients having COVID-19 in 2020-2021 with (1) historical control patients having influenza-like illness in 2018 and (2) contemporaneous control patients seen for wellness or preventive visits in 2020-2021.

RESULTS: We identified 28,215 patients with a COVID-19 diagnosis and 235,953 historical control patients with influenza-like illness. The COVID-19 group had higher prevalences of breathing difficulties (4.2% vs 1.9%), type 2 diabetes (12.0% vs 10.2%), fatigue (3.9% vs 2.2%), and sleep disturbances (3.5% vs 2.4%). There were no differences, however, in the postdiagnosis monthly trend in cumulative morbidity between the COVID-19 patients (trend = 0.026; 95% CI, 0.025-0.027) and the patients with influenza-like illness (trend = 0.026; 95% CI, 0.023-0.027). Relative to contemporaneous wellness control patients, COVID-19 patients had higher prevalences of breathing difficulties and type 2 diabetes.

CONCLUSIONS: Our findings show a moderate burden of post-COVID conditions in primary care, including breathing difficulties, fatigue, and sleep disturbances. Based on clinical registry data, the prevalence of post-COVID conditions in primary care practices is lower than that reported in subspecialty and hospital settings.}, } @article {pmid39038507, year = {2024}, author = {Wesley, UV and Dempsey, RJ}, title = {Neuro-molecular perspectives on long COVID-19 impacted cerebrovascular diseases - a role for dipeptidyl peptidase IV.}, journal = {Experimental neurology}, volume = {380}, number = {}, pages = {114890}, doi = {10.1016/j.expneurol.2024.114890}, pmid = {39038507}, issn = {1090-2430}, mesh = {Humans ; *Dipeptidyl Peptidase 4/metabolism ; *COVID-19/complications ; *Cerebrovascular Disorders ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) has caused immense devastation globally with many outcomes that are now extending to its long-term sequel called long COVID. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects not only lungs, but also the brain and heart in association with endothelial cell dysfunction, coagulation abnormalities, and thrombosis leading to cardio-cerebrovascular health issues. Fatigue, cognitive decline, and brain fog are common neurological symptoms in persisting long COVID. Neurodegenerative processes and SARS-CoV-2 infection manifest overlapping molecular mechanisms, such as cytokine dysregulation, inflammation, protein aggregation, mitochondrial dysfunction, and oxidative stress. Identifying the key molecules in these processes is of importance for prevention and treatment of this disease. In particular, Dipeptidyl peptidase IV (DPPIV), a multifunctional peptidase has recently drawn attention as a potential co-receptor for SARS-CoV-2 infection and cellular entry. DPPIV is a known co-receptor for some other COVID viruses including MERS-Co-V. DPPIV regulates the immune responses, obesity, glucose metabolism, diabetes, and hypertension that are associated with cerebrovascular manifestations including stroke. DPPIV likely worsens persisting COVID-19 by disrupting inflammatory signaling pathways and the neurovascular system. This review highlights the neurological, cellular and molecular processes concerning long COVID, and DPPIV as a potential key factor contributing to cerebrovascular dysfunctions following SARS-CoV-2 infection.}, } @article {pmid39037494, year = {2024}, author = {Boruch, A and Branchaw, G and O'Connor, PJ and Cook, DB}, title = {Physical Activity and Fatigue Symptoms: Neurotypical Adults and People with Chronic Multisymptom Illnesses.}, journal = {Current topics in behavioral neurosciences}, volume = {67}, number = {}, pages = {281-308}, pmid = {39037494}, issn = {1866-3370}, mesh = {Adult ; Humans ; Chronic Disease ; *Exercise/physiology ; *Fatigue/physiopathology ; *Fatigue Syndrome, Chronic/physiopathology ; Persian Gulf Syndrome/physiopathology ; Post-Acute COVID-19 Syndrome/physiopathology ; }, abstract = {For neurotypical adults, a single bout of low-to-moderate intensity physical activity usually transiently improves feelings of energy. Similar bouts of exercise have the opposite effect of increased feelings of fatigue when performed by samples with chronic multisymptom illnesses (CMIs) such as Long-COVID, Gulf War Illness (GWI), or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The short-term adoption of regular moderate intensity physical activity (typical experiments are 1 to 6 months) among neurotypical adults results in small-to-moderate improvements in self-reported feelings of fatigue, energy, and vitality. Small improvements in these feelings, or no change at all, occur for CMIs, but limited data precludes strong conclusions. The mechanisms of exercise effects on fatigue, whether acute or chronic, are poorly understood but likely involve multiple neural circuits and associated transmitters. For CMIs, the mechanisms of acute worsening of fatigue with exercise may be driven by the yet unknown pathophysiological mechanisms of the disease (perhaps involving brain, immune and autonomic system dysfunction, and their interactions). Likewise, fatigue improvements may depend on whether chronic physical activity is a disease-modifying treatment.}, } @article {pmid39037125, year = {2024}, author = {Zerón-Rugerio, MF and Zaragozá, MC and Domingo, JC and Sanmartín-Sentañes, R and Alegre-Martin, J and Castro-Marrero, J and Cambras, T}, title = {Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study.}, journal = {Chronobiology international}, volume = {41}, number = {8}, pages = {1104-1115}, doi = {10.1080/07420528.2024.2380020}, pmid = {39037125}, issn = {1525-6073}, mesh = {Humans ; Female ; Male ; *Fatigue Syndrome, Chronic/physiopathology ; *Circadian Rhythm/physiology ; Middle Aged ; Adult ; Prospective Studies ; *Sleep/physiology ; *COVID-19/complications/physiopathology ; Heart Disease Risk Factors ; Cardiovascular Diseases/physiopathology ; Post-Acute COVID-19 Syndrome ; Actigraphy ; Risk Factors ; SARS-CoV-2 ; Biomarkers/blood ; Vascular Cell Adhesion Molecule-1/blood ; }, abstract = {This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.}, } @article {pmid39036098, year = {2024}, author = {Carmona-Cervelló, M and León-Gómez, BB and Dacosta-Aguayo, R and Lamonja-Vicente, N and Montero-Alía, P and Molist, G and Ayet, A and Chacón, C and Costa-Garrido, A and López-Lifante, VM and Zamora-Putin, V and Liutsko, L and García-Sierra, R and Fornés, A and Moreno-Gabriel, E and Massanella, M and Muñoz-Moreno, JA and Rodríguez-Pérez, MC and Mateu, L and Prats, A and Mataró, M and Boigues, M and Quirant, B and Prado, JG and Martínez-Cáceres, E and Violán, C and Torán-Monserrat, P and , }, title = {Long COVID: cognitive, balance, and retina manifestations.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1399145}, pmid = {39036098}, issn = {2296-858X}, abstract = {BACKGROUND: The neurological symptoms of Long COVID (LC) and the impact of neuropsychological manifestations on people's daily lives have been extensively described. Although a large body of literature describes symptoms, validating this with objective measures is important. This study aims to identify and describe the effects of Long COVID on cognition, balance, and the retinal fundus, and determine whether the duration of symptoms influences cognitive impairment.

METHODS: This cross-sectional study involved LC volunteers with cognitive complaint from public health centers in northern Barcelona who participated between January 2022 and March 2023. This study collected sociodemographic characteristics, information on substance use, comorbidities, and clinical data related to COVID-19. We measured five cognitive domains using a battery of neuropsychological tests. Balance was assessed through posturography and retinal vascular involvement by retinography.

RESULTS: A total of 166 people with LC and cognitive complaints participated, 80.72% were women and mean age was 49.28 ± 8.39 years. The most common self-reported symptoms were concentration and memory deficit (98.80%), brain fog (82.53%) and insomnia (71.17%). The 68.67% presented cognitive deficit in at least one domain, with executive functions being the most frequent (43.98%). The 51.52% of the participants exhibited a dysfunctional pattern in balance, and 9.2% showed some alteration in the retina. There were no statistically significant differences between cognitive impairment and symptom duration.

CONCLUSION: Our findings contribute to a more comprehensive understanding of the pathology associated with Long COVID. They highlight the diversity of self-reported symptoms, the presence of abnormal balance patterns, and some cognitive impairment. These findings underscore the necessity of addressing the clinical management of this condition in primary care through follow-up and the pursuit of multidisciplinary and comprehensive treatment.}, } @article {pmid39035011, year = {2024}, author = {Notarte, KI and Carandang, THDC and Velasco, JV and Pastrana, A and Ver, AT and Manalo, GN and Ng, JA and Grecia, S and Lippi, G and Henry, BM and Fernández-de-Las-Peñas, C}, title = {Autoantibodies in COVID-19 survivors with post-COVID symptoms: a systematic review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1428645}, pmid = {39035011}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology ; *Autoantibodies/immunology/blood ; *SARS-CoV-2/immunology ; *Survivors ; }, abstract = {OBJECTIVE: The long-lasting persistence of autoantibodies stands as one of the hypotheses explaining the multisystemic manifestations seen in individuals with post-COVID-19 condition. The current review offers restricted insights into the persistence of autoantibodies in plasma/serum in people with post-COVID symptoms.

METHODS: PubMed/MEDLINE, CINAHL, EMBASE, and Web of Science databases, as well as on medRxiv and bioRxiv preprint servers were searched up to January 5[th], 2024. Papers investigating the presence of autoantibodies in plasma/serum samples in people with post-COVID symptoms were included. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality.

RESULTS: From 162 identified records, five articles met all inclusion criteria; four studies included infected controls with no post-COVID symptoms whereas all five studies included non-infected controls (410 COVID-19 survivors with post-COVID symptoms, 223 COVID-19 survivors with no post-COVID symptoms as controls and 266 non-infected healthy controls). Four studies concluded that the presence of autoantibodies had a potential (but small) role in post-COVID-19 condition whereas one study concluded that autoantibodies were not associated. Quality assessment showed all studies had high methodological quality.

CONCLUSION: Although evidence suggests that persistent autoantibodies can be associated with post-COVID symptoms, the clinical relevance of their presence seems modest at this stage. Current results highlight further research to clarify the role of autoantibodies in the development of post-COVID symptoms, guiding the development of tailored diagnostic and treatment approaches to enhance patient outcomes.

https://osf.io/vqz28.}, } @article {pmid39034937, year = {2024}, author = {Kozłowski, P and Leszczyńska, A and Ciepiela, O}, title = {Long COVID Definition, Symptoms, Risk Factors, Epidemiology and Autoimmunity: A Narrative Review.}, journal = {American journal of medicine open}, volume = {11}, number = {}, pages = {100068}, pmid = {39034937}, issn = {2667-0364}, abstract = {The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, and the global economy. In order to save as many lives as possible, precautions such as social distancing, quarantine, and testing policies were implemented, and effective vaccines were developed. A growing amount of data collected worldwide allowed the characterization of this new disease, which turned out to be more complex than other common respiratory tract infections. An increasing number of convalescents presented with a variety of nonspecific symptoms emerging after the acute infection. This possible new global health problem was identified and labelled as long COVID. Since then, a great effort has been made by clinicians and the scientific community to understand the underlying mechanisms and to develop preventive measures and effective treatment. The role of autoimmunity induced by SARS-CoV-2 infection in the development of long COVID is discussed in this review. We aim to deliver a description of several conditions with an autoimmune background observed in COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome and related thrombosis, and Kawasaki disease highlighting a relationship between SARS-CoV-2 infection and the development of autoimmunity. However, further studies are required to determine its true clinical significance.}, } @article {pmid39034480, year = {2024}, author = {Hyland, ME and Antonacci, Y and Bacon, AM}, title = {Comparison of the symptom networks of long-COVID and chronic fatigue syndrome: From modularity to connectionism.}, journal = {Scandinavian journal of psychology}, volume = {65}, number = {6}, pages = {1132-1140}, doi = {10.1111/sjop.13060}, pmid = {39034480}, issn = {1467-9450}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology/diagnosis ; Female ; Male ; Adult ; Cross-Sectional Studies ; *COVID-19/psychology/complications ; Middle Aged ; *Fibromyalgia/psychology ; *Irritable Bowel Syndrome/psychology/diagnosis ; Medically Unexplained Symptoms ; Surveys and Questionnaires ; Asthma/psychology/complications ; }, abstract = {The objective was to compare the symptom networks of long-COVID and chronic fatigue syndrome (CFS) in conjunction with other theoretically relevant diagnoses in order to provide insight into the etiology of medically unexplained symptoms (MUS). This was a cross-sectional comparison of questionnaire items between six groups identified by clinical diagnosis. All participants completed a 65-item psychological and somatic symptom questionnaire (GSQ065). Diagnostically labelled groups were long-COVID (N = 107), CFS (N = 254), irritable bowel syndrome (IBS, N = 369), fibromyalgia (N = 1,127), severe asthma (N = 100) and healthy group (N = 207). The 22 symptoms that best discriminated between the six groups were selected for network analysis. Connectivity, fragmentation and number of symptom clusters (statistically related symptoms) were assessed. Compared to long-COVID, the symptom networks of CFS, IBS and fibromyalgia had significantly lower connectivity, greater fragmentation and more symptom clusters. The number of clusters varied between 9 for CFS and 3 for severe asthma, and the content of clusters varied across all groups. Of the 33 symptom clusters identified over the six groups 30 clusters were unique. Although the symptom networks of long-COVID and CFS differ, the variation of cluster content across the six groups is inconsistent with a modular causal structure but consistent with a connectionist (network, parallel distributed processing) biological basis of MUS. A connectionist structure would explain why symptoms overlap and merge between different functional somatic syndromes, the failure to discover a biological diagnostic test and how psychological and behavioral interventions are therapeutic.}, } @article {pmid39033016, year = {2024}, author = {Twycross, A and Barnard, M}, title = {Patient-centred approaches are key to improving Long Covid healthcare access.}, journal = {Evidence-based nursing}, volume = {}, number = {}, pages = {}, doi = {10.1136/ebnurs-2024-104070}, pmid = {39033016}, issn = {1468-9618}, } @article {pmid39032365, year = {2024}, author = {Allen, SF and van der Feltz-Cornelis, CM}, title = {Social pain. Comment on 'Environmental factors and their impact on chronic pain development and maintenance' by Morena Brazil Sant'Anna, Louise Faggionato Kimura, Willians Fernando Vieira, Vanessa Olzon Zambelli, Leonardo Santana Novaes, Natália Gabriele Hösch, Gisele Picolo.}, journal = {Physics of life reviews}, volume = {50}, number = {}, pages = {120-122}, doi = {10.1016/j.plrev.2024.07.004}, pmid = {39032365}, issn = {1873-1457}, mesh = {Humans ; *Chronic Pain ; Environment ; }, } @article {pmid39119366, year = {2023}, author = {Kow, CS and Ramachandram, DS and Hasan, SS}, title = {Management of long COVID fatigue: the overlooked impact of anemia.}, journal = {Hippokratia}, volume = {27}, number = {3}, pages = {117}, pmid = {39119366}, issn = {1108-4189}, } @article {pmid39324014, year = {2023}, author = {Oladejo, SO and Watson, LR and Watson, BW and Rajaratnam, K and Kotze, MJ and Kell, DB and Pretorius, E}, title = {Data sharing: A Long COVID perspective, challenges, and road map for the future.}, journal = {South African journal of science}, volume = {119}, number = {5-6}, pages = {73-80}, pmid = {39324014}, issn = {0038-2353}, support = {U01 MH127704/MH/NIMH NIH HHS/United States ; }, abstract = {'Long COVID' is the term used to describe the phenomenon in which patients who have survived a COVID-19 infection continue to experience prolonged SARS-CoV-2 symptoms. Millions of people across the globe are affected by Long COVID. Solving the Long COVID conundrum will require drawing upon the lessons of the COVID-19 pandemic, during which thousands of experts across diverse disciplines such as epidemiology, genomics, medicine, data science, and computer science collaborated, sharing data and pooling resources to attack the problem from multiple angles. Thus far, there has been no global consensus on the definition, diagnosis, and most effective treatment of Long COVID. In this work, we examine the possible applications of data sharing and data science in general with a view to, ultimately, understand Long COVID in greater detail and hasten relief for the millions of people experiencing it. We examine the literature and investigate the current state, challenges, and opportunities of data sharing in Long COVID research.}, } @article {pmid39177849, year = {2023}, author = {Strumann, C and von Meißner, WCG and Blickle, PG and Steinhäuser, J}, title = {The ambulatory care of patients with post-acute sequelae of COVID-19.}, journal = {Research in health services & regions}, volume = {2}, number = {1}, pages = {4}, pmid = {39177849}, issn = {2730-9827}, abstract = {BACKGROUND: There is an increasing number of patients that do not make a rapid or full recovery from a SARS-CoV-2 infection, the Coronavirus Disease 2019 (COVID-19) and suffer from the so-called "long-COVID" or post-acute sequelae of COVID-19 (PASC). The long-term implications for health services are expected to be substantial. The objective of this analysis was to estimate the utilization of outpatient services from primary and secondary care. Further, we evaluated the multidisciplinary ambulatory care management of PASC patients in Germany.

METHODS: All members of the Physician network "MEDI Baden-Württemberg e.V.", i.e., 1,263 primary care physicians (PCPs) and 1,772 specialists working in secondary care were invited to participate in a questionnaire surveying routine data regarding the general care situation at the physician practice level of patients suffering from PASC. Bivariate analyses were applied to consider potential differences between primary and secondary care.

RESULTS: In total, 194 physicians participated in this survey (response rates of 9.6% (primary care) and 4.1% (secondary care). On average, each physician treated 31.9 PASC patients. Most PASC patients (61.2%) had three or more long-COVID symptoms. On average, 10.6 PASC patients visited a physicians' practice per quarter. The additional consulting effort for treating PASC patients was 34.1 min (median: 20 min) and higher in primary care. Most PCPs (71.1%) integrated secondary care in the treatment of their PASC patients. Less than half of the PASC patients (42.0%) sought secondary care with a referral from primary care. 5.7 patients visited the physicians' practices per week, who were concerned about suffering from PASC without any following medical confirmation. This caused an average additional effort for the physicians of 17.5 min per visit. There were no differences between rural and urban areas.

CONCLUSION: Our results reveal that there is a substantial additional consulting effort for treating PASC patients that is especially high in primary care. The additional consulting effort results from the consultation of a particular high number of patients that are concerned about suffering from PACS without a following medical confirmation. To guarantee a high quality and adequate provision of care for a potentially further increasing number of concerned patients, the ambulatory health services should be strengthened and adequately compensated.}, } @article {pmid39076856, year = {2023}, author = {Kusumawardhani, NY and Putra, ICS and Kamarullah, W and Afrianti, R and Pramudyo, M and Iqbal, M and Prameswari, HS and Achmad, C and Tiksnadi, BB and Akbar, MR}, title = {Cardiovascular Disease in Post-Acute COVID-19 Syndrome: A Comprehensive Review of Pathophysiology and Diagnosis Approach.}, journal = {Reviews in cardiovascular medicine}, volume = {24}, number = {1}, pages = {28}, pmid = {39076856}, issn = {2153-8174}, abstract = {Long COVID or post-acute Coronavirus disease 2019 (COVID-19), a malady defined by the persistence of COVID-19 symptoms for weeks or even months, is expected to affect the lives of millions of individuals worldwide significantly. Cardiopulmonary symptoms such as chest discomfort, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia syndrome, and arrhythmias are prevalent and widely recognized. A variety of cardiovascular problems, including myocardial inflammation, myocardial infarction, ventricular dysfunction, and endothelial dysfunction, have been described in individuals following the initial acute phase. With over 10,000 published publications on COVID-19 and the cardiovascular system, presenting an unbiased thorough analysis of how SARS-CoV-2 affects the system is essentially challenging. This review will provide an overview of frequent cardiovascular manifestations, emphasizing consequences, proposed pathophysiology, and clinical diagnostic manifestation strategy.}, } @article {pmid39086962, year = {2022}, author = {Brock, S and Jackson, DB and Soldatos, TG and Hornischer, K and Schäfer, A and Diella, F and Emmert, MY and Hoerstrup, SP}, title = {Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms.}, journal = {Frontiers in molecular medicine}, volume = {2}, number = {}, pages = {1035290}, pmid = {39086962}, issn = {2674-0095}, abstract = {Infection with SARS-CoV-2 coronavirus causes systemic, multi-faceted COVID-19 disease. However, knowledge connecting its intricate clinical manifestations with molecular mechanisms remains fragmented. Deciphering the molecular basis of COVID-19 at the whole-patient level is paramount to the development of effective therapeutic approaches. With this goal in mind, we followed an iterative, expert-driven process to compile data published prior to and during the early stages of the pandemic into a comprehensive COVID-19 knowledge model. Recent updates to this model have also validated multiple earlier predictions, suggesting the importance of such knowledge frameworks in hypothesis generation and testing. Overall, our findings suggest that SARS-CoV-2 perturbs several specific mechanisms, unleashing a pathogenesis spectrum, ranging from "a perfect storm" triggered by acute hyper-inflammation, to accelerated aging in protracted "long COVID-19" syndromes. In this work, we shortly report on these findings that we share with the community via 1) a synopsis of key evidence associating COVID-19 symptoms and plausible mechanisms, with details presented within 2) the accompanying "COVID-19 Explorer" webserver, developed specifically for this purpose (found at https://covid19.molecularhealth.com). We anticipate that our model will continue to facilitate clinico-molecular insights across organ systems together with hypothesis generation for the testing of potential repurposing drug candidates, new pharmacological targets and clinically relevant biomarkers. Our work suggests that whole patient knowledge models of human disease can potentially expedite the development of new therapeutic strategies and support evidence-driven clinical hypothesis generation and decision making.}, } @article {pmid39726831, year = {2023}, author = {Williams, N}, title = {Covid-19, Diagnostic History and Mortality from Medicare 1999-2021, In an All-Cause Mortality Approach.}, journal = {Archives of internal medicine research}, volume = {6}, number = {4}, pages = {74-85}, pmid = {39726831}, issn = {2688-5654}, support = {Z99 LM999999/ImNIH/Intramural NIH HHS/United States ; }, abstract = {INTRODUCTION: SARS-CoV-2 infections co-occurred with other diverse pre-existing clinical conditions in mortality cases. We use encounter level health data to evaluate the impact of non-Covid-19 diagnostic events on all-cause mortality observed among Covid-19 positive cases billing Medicare. We further investigate prior diagnostic codes which occur in pre-pandemic study years among cases presenting to Medicare clinically with Covid-19 and cases with Covid-19 who experience all-cause mortality to inform patient population management.

METHODS: We aggregated encounter level records sourced from all Medicare beneficiaries from 1999-2021. Odds ratios were constructed using diagnostic history, age decile, study year and survival status.We used Generalized Linear Model (GLM) to predict the Decedent Observation Odds Ratio (DOOR) from study year, case observation odds ratio, age decile, non-covid conditions within counts of distinct covid-ever cases and their decedents. Odds ratios are relative to covid-never cases, or cases who did not present with Covid-19 clinically.

RESULTS: High explanatory DOOR measures are observed for diagnostic codes commonly associated with inpatient Covid-19 mortality. High DOOR measures are also observed for individuals living with specific kinds of cancers, experiencing cardiac arrest or acute tubular necrosis.

CONCLUSION: Covid-ever mortality is influenced by primary infection itself and exacerbations of pre-existing conditions. Consequences of primary infection are observable in GLM, as well as meaningful prior clinical risk factors such as cancer, diabetes, cardiac and respiratory disease. Long-covid conditions require surviving Covid-19 clinical presentation and are predictable from GLM models.}, } @article {pmid39354971, year = {2022}, author = {Lopes van den Broek, S and García-Vázquez, R and Andersen, IV and Valenzuela-Nieto, G and Shalgunov, V and Battisti, UM and Schwefel, D and Modhiran, N and Kramer, V and Cheuquemilla, Y and Jara, R and Salinas-Varas, C and Amarilla, AA and Watterson, D and Rojas-Fernandez, A and Herth, MM}, title = {Development and evaluation of an [18]F-labeled nanobody to target SARS-CoV-2's spike protein.}, journal = {Frontiers in nuclear medicine}, volume = {2}, number = {}, pages = {1033697}, pmid = {39354971}, issn = {2673-8880}, abstract = {COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) - a small, engineered protein derived from alpacas - and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to [18]F-label the NB under mild conditions once the NBs were successfully modified with trans-cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.}, } @article {pmid39044915, year = {2022}, author = {Wannasewok, K and Suraaroonsamrit, B and Jeungsiragulwit, D and Udomratn, P}, title = {Development of Community Mental Health Infrastructure in Thailand: From the Past to the COVID-19 Pandemic.}, journal = {Consortium psychiatricum}, volume = {3}, number = {3}, pages = {95-106}, pmid = {39044915}, issn = {2713-2919}, abstract = {Thailand is an upper middle-income country located in the center of mainland Southeast Asia with a population of 66.17 million as of 2021. The aim of this review article is to illustrate the development of community mental health in our country. We have divided the article into five main sections: namely, the mental health service infrastructure, the community mental health system, human resources, mental health financing, public education, and links to other sectors. Mental health care has been integrated into primary care since 1982, resulting in a major shift in focus on mental health at the community level; however, mental health problems and the mental health gap in service accessibility remain present, especially during the current COVID-19 pandemic. Community mental health care has been extended to networks outside the health care system, including the community authorities. It has been provided with psychiatric care and rehabilitation, together with the promotion of mental health and prevention of mental disorders for improving accessibility to services, especially during a pandemic situation. Finally, future challenges to face community mental health have been outlined, such as insufficient staff to develop rehabilitation service facilities for people with chronic, serious mental illnesses; identifying supporting funding from other stakeholders; and mental health care for persons with long COVID living in the community.}, } @article {pmid39483361, year = {2022}, author = {Colombo, J and Weintraub, MI and Munoz, R and Verma, A and Ahmad, G and Kaczmarski, K and Santos, L and DePace, NL}, title = {Long COVID and the Autonomic Nervous System: The Journey from Dysautonomia to Therapeutic Neuro-Modulation through the Retrospective Analysis of 152 Patients.}, journal = {NeuroSci}, volume = {3}, number = {2}, pages = {300-310}, pmid = {39483361}, issn = {2673-4087}, abstract = {INTRODUCTION: The severity and prevalence of Post-Acute COVID-19 Sequela (PACS) or long-COVID syndrome (long COVID) should not be a surprise. Long-COVID symptoms may be explained by oxidative stress and parasympathetic and sympathetic (P&S) dysfunction. This is a retrospective, hypothesis generating, outcomes study.

METHODS: From two suburban practices in northeastern United States, 152 long COVID patients were exposed to the following practices: (1) first, they were P&S tested (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) prior to being infected with COVID-19 due to other causes of autonomic dysfunction; (2) received a pre-COVID-19 follow-up P&S test after autonomic therapy; (3) then, they were infected with COVID-19; (4) P&S tested within three months of surviving the COVID-19 infection with long-COVID symptoms; and, finally, (5) post-COVID-19, follow-up P&S tested, again, after autonomic therapy. All the patients completed autonomic questionnaires with each test. This cohort included 88 females (57.8%), with an average age of 47.0 years (ranging from 14 to 79 years), and an average BMI of 26.9 #/in[2].

RESULTS: More pre-COVID-19 patients presented with sympathetic withdrawal than parasympathetic excess. Post-COVID-19, these patients presented with this ratio reversed and, on average, 49.9% more autonomic symptoms than they did pre-COVID-19.

DISCUSSION: Both parasympathetic excess and sympathetic withdrawal are separate and treatable autonomic dysfunctions and autonomic treatment significantly reduces the prevalence of autonomic symptoms.

CONCLUSION: SARS-CoV-2, via its oxidative stress, can lead to P&S dysfunction, which, in turn, affects the control and coordination of all systems throughout the whole body and may explain all of the symptoms of long-COVID syndrome. Autonomic therapy leads to positive outcomes and patient quality of life may be restored.}, } @article {pmid39195986, year = {2022}, author = {Giacca, M and Shah, AM}, title = {The pathological maelstrom of COVID-19 and cardiovascular disease.}, journal = {Nature cardiovascular research}, volume = {1}, number = {3}, pages = {200-210}, pmid = {39195986}, issn = {2731-0590}, support = {MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; RE/18/2/34213//British Heart Foundation (BHF)/ ; RG/19/11/34633//British Heart Foundation (BHF)/ ; CH/1999001/11735//British Heart Foundation (BHF)/ ; 787971//EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a consequence of infection of the upper and lower respiratory tract with severe acute respiratory syndrome coronavirus 2 but often becomes a systemic disease, with important involvement of other organs. A bidirectional relationship exists between COVID-19 and cardiovascular disease. On the one hand, preexisting comorbidities, in particular high prevalence of cardiovascular risk factors such as hypertension and diabetes and chronic cardiovascular conditions predispose to severe disease. On the other hand, biomarkers of myocardial injury are frequently raised in patients with COVID-19, along with arrhythmia and heart failure. Localized thrombosis is a common finding in the lungs but can also increase the occurrence of thrombotic events systemically. Thrombosis is consequent to different pathogenic mechanisms, which include endothelial dysfunction and immunothrombosis. Thrombocytopenia is common in patients with COVID-19 and alterations in platelet function participate in the pro-thrombotic phenotype. Involvement of the cardiovascular system in COVID-19 has important consequences during recovery from infection and the development of long COVID.}, } @article {pmid39031491, year = {2024}, author = {Greenhalgh, T and Darbyshire, J and Ladds, E and Van Dael, J and Rayner, C}, title = {Working knowledge, uncertainty and ontological politics: An ethnography of UK long covid clinics.}, journal = {Sociology of health & illness}, volume = {46}, number = {8}, pages = {1881-1900}, doi = {10.1111/1467-9566.13819}, pmid = {39031491}, issn = {1467-9566}, support = {COV-LT-0016//National Institute for Health and Care Research/ ; }, mesh = {Humans ; United Kingdom ; *COVID-19/psychology ; *Anthropology, Cultural ; Uncertainty ; *SARS-CoV-2 ; Politics ; Post-Acute COVID-19 Syndrome ; Patient Care Team ; }, abstract = {Long covid (persistent COVID-19) is a new disease with contested aetiology and variable prognosis. We report a 2-year ethnography of UK long covid clinics. Using a preformative lens, we show that multidisciplinary teams (MDTs) built working knowledge based on shared practices, mutual trust, distributed cognition (e.g. emails, record entries), relational knowledge of what was at stake for the patient, and harnessing uncertainty to open new discursive spaces. Most long covid MDTs performed the working knowledge of 'rehabilitation', a linked set of practices oriented to ensuring that the patient understood and strove to 'correct' maladaptive physiological responses (e.g. through breathing exercises) and pursued recovery goals, supported by physiotherapists, psychologists and generalist clinicians. Some MDTs with a higher proportion of doctors (e.g. cardiologists, neurologists, immunologists) enacted the working knowledge of 'microscopic damage', seeking to elucidate and rectify long covid's underlying molecular and cellular pathology. They justified non-standard investigations and medication in selected patients by co-constructing an evidentiary narrative based on biological mechanisms. Working knowledge was ontologically concordant within MDTs but sometimes discordant between MDTs. Overt ontological conflict occurred mostly when patients attending 'rehabilitation' clinics invoked the working knowledge of microscopic damage that had been generated and circulated in online support communities.}, } @article {pmid39029889, year = {2024}, author = {Beugelink, JW and Hóf, H and Janssen, BJC}, title = {CRTAC1 has a Compact β-propeller-TTR Core Stabilized by Potassium Ions.}, journal = {Journal of molecular biology}, volume = {436}, number = {18}, pages = {168712}, doi = {10.1016/j.jmb.2024.168712}, pmid = {39029889}, issn = {1089-8638}, mesh = {Humans ; Calcium/metabolism/chemistry ; *Calcium-Binding Proteins/chemistry/metabolism/genetics ; Crystallography, X-Ray ; Ions/metabolism/chemistry ; Models, Molecular ; *Potassium/metabolism/chemistry ; Protein Conformation ; }, abstract = {Cartilage acidic protein-1 (CRTAC1) is a secreted glycoprotein with roles in development, function and repair of the nervous system. It is linked to ischemic stroke, osteoarthritis and (long) COVID outcomes, and has suppressive activity in carcinoma and bladder cancer. Structural characterization of CRTAC1 has been complicated by its tendency to form disulfide-linked aggregates. Here, we show that CRTAC1 is stabilized by potassium ions. Using x-ray crystallography, we determined the structure of CRTAC1 to 1.6 Å. This reveals that the protein consists of a three-domain fold, including a previously-unreported compact β-propeller-TTR combination, in which an extended loop of the TTR plugs the β-propeller core. Electron density is observed for ten bound ions: six calcium, three potassium and one sodium. Low potassium ion concentrations lead to changes in tryptophan environment and exposure of two buried free cysteines located on a β-blade and in the β-propeller-plugging TTR loop. Mutating the two free cysteines to serines prevents covalent intermolecular interactions, but not aggregation, in absence of potassium ions. The potassium ion binding sites are located between the blades of the β-propeller, explaining their importance for the stability of the CRTAC1 fold. Despite varying in sequence, the three potassium ion binding sites are structurally similar and conserved features of the CRTAC protein family. These insights into the stability and structure of CRTAC1 provide a basis for further work into the function of CRTAC1 in health and disease.}, } @article {pmid39029739, year = {2024}, author = {Nugent, K and Berdine, G}, title = {Dyspnea and long COVID patients.}, journal = {The American journal of the medical sciences}, volume = {368}, number = {4}, pages = {399-404}, doi = {10.1016/j.amjms.2024.07.024}, pmid = {39029739}, issn = {1538-2990}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Dyspnea/etiology/physiopathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Respiratory Function Tests ; Exercise Test ; }, abstract = {Patients with prior COVID-19 infections often develop chronic post-COVID symptoms, such as fatigue and dyspnea. Some patients have residual pulmonary disorders with abnormal pulmonary function tests and/or chest radiographs to explain their dyspnea. However, other patients appear to have dyspnea that is out of proportion to any measurable change in lung function. Some of these patients have abnormal cardiopulmonary exercise testing with definite cardiac or respiratory limits. However, others have normal cardiopulmonary exercise testing based on VO2 measurement but pronounced dyspnea during this testing. These patients often have abnormal respiratory patterns, referred to as dysfunctional breathing, with irregular and variable respiratory rates and/or tidal volumes. Consequently, their control of breathing is impaired, and this may represent residual effects from prior COVID-19 infection involving the central nervous system. Alternatively, patients may have acquired "a memory" of respiratory symptoms during their infection which persists post-infection. These patients should participate in pulmonary rehabilitation and breathing retraining.}, } @article {pmid39028694, year = {2024}, author = {Leibel, SL and McVicar, RN and Murad, R and Kwong, EM and Clark, AE and Alvarado, A and Grimmig, BA and Nuryyev, R and Young, RE and Lee, JC and Peng, W and Zhu, YP and Griffis, E and Nowell, CJ and James, B and Alarcon, S and Malhotra, A and Gearing, LJ and Hertzog, PJ and Galapate, CM and Galenkamp, KMO and Commisso, C and Smith, DM and Sun, X and Carlin, AF and Sidman, RL and Croker, BA and Snyder, EY}, title = {A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {30}, pages = {e2408109121}, pmid = {39028694}, issn = {1091-6490}, support = {R01 HL157985/HL/NHLBI NIH HHS/United States ; R01 CA207189/CA/NCI NIH HHS/United States ; DISC2COVID19-12022//California Institute for Regenerative Medicine (CIRM)/ ; T32 HL166127/HL/NHLBI NIH HHS/United States ; AI036214//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; S10 OD026929/OD/NIH HHS/United States ; P30 AI036214/AI/NIAID NIH HHS/United States ; 3R01CA207189-05S1//HHS | NIH | National Cancer Institute (NCI)/ ; }, mesh = {Humans ; *SARS-CoV-2/physiology/immunology ; *COVID-19/immunology/virology ; *Lung/virology/immunology/pathology ; *Virus Internalization ; *Organoids/virology ; COVID-19 Drug Treatment ; Induced Pluripotent Stem Cells/virology ; Angiotensin-Converting Enzyme 2/metabolism ; Inflammation ; Cytokines/metabolism ; Apoptosis ; }, abstract = {The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic.}, } @article {pmid39027374, year = {2024}, author = {Hurler, L and Mescia, F and Bergamaschi, L and , and Kajdácsi, E and Sinkovits, G and Cervenak, L and Prohászka, Z and Lyons, PA and Toonen, EJM}, title = {sMR and PTX3 levels associate with COVID-19 outcome and survival but not with Long COVID.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110162}, pmid = {39027374}, issn = {2589-0042}, abstract = {Biomarkers for monitoring COVID-19 disease course are lacking. Study aim was to identify biomarkers associated with disease severity, survival, long-term outcome, and Long COVID. As excessive macrophages activation is a hallmark of COVID-19 and complement activation is key in this, we selected the following proteins involved in these processes: PTX3, C1q, C1-INH, C1s/C1-INH, and sMR. EDTA-plasma concentrations were measured in 215 patients and 47 controls using ELISA. PTX3, sMR, C1-INH, and C1s/C1-INH levels were associated with disease severity. PTX3 and sMR were also associated with survival and long-term immune recovery. Lastly, sMR levels associate with ICU admittance. sMR (AUC 0.85) and PTX3 (AUC 0.78) are good markers for disease severity, especially when used in combination (AUC 0.88). No association between biomarker levels and Long COVID was observed. sMR has not previously been associated with COVID-19 disease severity, ICU admittance or survival and may serve as marker for disease course.}, } @article {pmid39027081, year = {2024}, author = {Deng, S and Yin, M and Chen, Z and Deng, J and Wang, Z and Li, Y and Lyu, M and Zhang, B and Zhu, S and Hu, S and Nassis, GP and Li, Y}, title = {SARS-CoV-2 infection decreases cardiorespiratory fitness and time-trial performance even two months after returning to regular training - Insights from a longitudinal case series of well-trained kayak athletes.}, journal = {Journal of exercise science and fitness}, volume = {22}, number = {4}, pages = {350-358}, pmid = {39027081}, issn = {1728-869X}, abstract = {OBJECTIVE: The aims of this study were to examine the effect of SARS-CoV-2 infection on cardiorespiratory fitness (CRF) and time-trial performance in vaccinated well-trained young kayak athletes.

METHODS: This is a longitudinal observational study. Sixteen (7 male, 9 female) vaccinated kayakers underwent body composition assessment, maximal graded exercise test, and 1000-m time-trial tests 21.9 ± 1.7 days before and 66.0 ± 2.2 days after the SARS-CoV-2 infection. The perception of training load was quantified with Borg's CR-10 scale before and after the infection return to sport period.

RESULTS: There were significant decreases in peak oxygen uptake (-9.7 %; effect size [ES] = 1.38), peak oxygen pulse (-5.7 %; ES = 0.96), and peak heart rate (-1.9 %; ES = 0.61). Peak minute ventilation, and minute ventilation/carbon dioxide production slope were unchanged after infection compared to the pre-infection values. In the entire 1000-m, the impaired tendencies were found in completion time, mean power, and mean speed (-2.4 to 1.2 %; small ESs = -0.40 to 0.47) as well as significant changes in stroke rate and stroke length (-4.5 to 3.7 %; ESs = -0.60 to 0.73).

CONCLUSION: SARS-CoV-2 infection decreased CRF and time-trial performance even two months after return to regular training in vaccinated athletes.}, } @article {pmid39026549, year = {2024}, author = {Grippo, F and Minelli, G and Crialesi, R and Marchetti, S and Pricci, F and Onder, G}, title = {Deaths related to post-COVID in Italy: a national study based on death certificates.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1401602}, pmid = {39026549}, issn = {2296-858X}, abstract = {INTRODUCTION: SARS-CoV-2 infection has been associated with the onset or persistence of symptoms in the long-term after the acute infection is resolved. This condition known as Post-COVID, might be particularly severe and potentially life-threatening. However, little is known on the impact of post-COVID condition on mortality. Aim of the present study is to assess and quantify Post-COVID deaths in Italy in years 2020 and 2021, based on an analysis of death certificates.

METHODS: Data from the Italian National Cause of Death Register were analyzed. ICD-10 code U09.9, released by the World Health Organization in September 2020, was used to identify the 'Post-COVID' condition. Numbers of post-COVID deaths from October 2020 to December 2021 were analyzed. Rates of post-COVID deaths were calculated for the year 2021.

RESULTS: Between October 2020 and December 2021, 4,752 death certificates reporting post-COVID condition were identified. Of these, 14.9% (n = 706) occurred between October and December 2020 and 85.1% (n = 4,046) in 2021. In 46.0% of post-COVID-related deaths, the underlying cause of death was COVID-19. Other frequent underlying causes were heart disease (14.3% of cases), neoplasms (9.2%), cerebrovascular diseases (6.3%) and Alzheimer's disease and other dementias (5.5%). The mortality rate related to post-COVID conditions in year 2021 was 5.1 deaths per 100 thousand inhabitants and it increased with increasing age. Men showed a higher mortality rate than women (4.3 deaths per 100 thousand in women and 6.0 deaths per 100 thousand in men).

DISCUSSION: Post-COVID conditions contributed to a substantial number of deaths in Italy. Strategies to identify the population at risk of severe long-term consequences of SARS-CoV-2 infection and interventions aimed at reducing this risk must be developed.}, } @article {pmid39026070, year = {2024}, author = {Kudiabor, H}, title = {Long COVID lung damage linked to immune system response.}, journal = {Nature}, volume = {631}, number = {8022}, pages = {717-718}, pmid = {39026070}, issn = {1476-4687}, mesh = {Animals ; Humans ; Mice ; *Immune System/drug effects/immunology/virology ; *Lung/drug effects/immunology/pathology/virology ; *Post-Acute COVID-19 Syndrome/complications/drug therapy/immunology/pathology ; SARS-CoV-2/immunology/pathogenicity ; *Inflammation/drug therapy/etiology/immunology/virology ; *Interferon-gamma/antagonists & inhibitors ; }, } @article {pmid39025516, year = {2024}, author = {Soriano, JB and Ancochea, J}, title = {Murder, she wrote: a long story on long COVID is being written.}, journal = {The European respiratory journal}, volume = {64}, number = {1}, pages = {}, doi = {10.1183/13993003.00916-2024}, pmid = {39025516}, issn = {1399-3003}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Homicide ; Post-Acute COVID-19 Syndrome ; Female ; }, } @article {pmid39025107, year = {2024}, author = {Oliveira, DN and Tavares-Júnior, JWL and Feitosa, WLQ and Cunha, LCV and Gomes, CMP and Moreira-Nunes, CA and Silva, JBSD and Sousa, AVM and Gaspar, SB and Sobreira, EST and Oliveira, LLB and Montenegro, RC and Moraes, MEA and Sobreira-Neto, MA and Braga-Neto, P}, title = {Long-COVID olfactory dysfunction: allele E4 of apolipoprotein E as a possible protective factor.}, journal = {Arquivos de neuro-psiquiatria}, volume = {82}, number = {9}, pages = {1-7}, doi = {10.1055/s-0044-1788272}, pmid = {39025107}, issn = {1678-4227}, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Middle Aged ; Prospective Studies ; *Olfaction Disorders/genetics ; Cross-Sectional Studies ; *Alleles ; Apolipoprotein E4/genetics ; Aged ; Adult ; Protective Factors ; Apolipoproteins E/genetics ; Polymorphism, Genetic ; SARS-CoV-2 ; Genotype ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity. As far as we know, no publications found significant associations between this disease's severity, OD, and APOE polymorphisms (E2, E3, and E4).

OBJECTIVE:  To analyze the epidemiology of OD and its relationship with APOE polymorphisms in a cohort of Long-COVID patients.

METHODS:  We conducted a prospective cohort study with patients followed in a post-COVID neurological outpatient clinic, with OD being defined as a subjective reduction of olfactory function after infection, and persistent OD being defined when the complaint lasted more than 3 months after the COVID-19 infection resolution. This cross-sectional study is part of a large research with previously reported data focusing on the cognitive performance of our sample.

RESULTS:  The final sample comprised 221 patients, among whom 186 collected blood samples for APOE genotyping. The persistent OD group was younger and had a lower hospitalization rate during the acute phase of the disease (p < 0.001). Furthermore, the APOE variant E4 allele frequency was lower in this group (p = 0.035). This study evaluated OD in an outpatient population with COVID-19. In the current literature on this disease, anosmia is associated with better clinical outcomes and the E4 allele is associated with worse outcomes.

CONCLUSION:  Our study provides new information to these correlations, suggesting APOE E4 as a protective factor for OD.}, } @article {pmid39024001, year = {2024}, author = {Benny, D and Giacobini, M and Catalano, A and Costa, G and Gnavi, R and Ricceri, F}, title = {A Multimorbidity Analysis of Hospitalized Patients With COVID-19 in Northwest Italy: Longitudinal Study Using Evolutionary Machine Learning and Health Administrative Data.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e52353}, pmid = {39024001}, issn = {2369-2960}, mesh = {Humans ; *COVID-19/epidemiology ; *Multimorbidity ; *Machine Learning ; Italy/epidemiology ; Male ; Female ; Aged ; *Hospitalization/statistics & numerical data ; Middle Aged ; Longitudinal Studies ; Aged, 80 and over ; }, abstract = {BACKGROUND: Multimorbidity is a significant public health concern, characterized by the coexistence and interaction of multiple preexisting medical conditions. This complex condition has been associated with an increased risk of COVID-19. Individuals with multimorbidity who contract COVID-19 often face a significant reduction in life expectancy. The postpandemic period has also highlighted an increase in frailty, emphasizing the importance of integrating existing multimorbidity details into epidemiological risk assessments. Managing clinical data that include medical histories presents significant challenges, particularly due to the sparsity of data arising from the rarity of multimorbidity conditions. Also, the complex enumeration of combinatorial multimorbidity features introduces challenges associated with combinatorial explosions.

OBJECTIVE: This study aims to assess the severity of COVID-19 in individuals with multiple medical conditions, considering their demographic characteristics such as age and sex. We propose an evolutionary machine learning model designed to handle sparsity, analyzing preexisting multimorbidity profiles of patients hospitalized with COVID-19 based on their medical history. Our objective is to identify the optimal set of multimorbidity feature combinations strongly associated with COVID-19 severity. We also apply the Apriori algorithm to these evolutionarily derived predictive feature combinations to identify those with high support.

METHODS: We used data from 3 administrative sources in Piedmont, Italy, involving 12,793 individuals aged 45-74 years who tested positive for COVID-19 between February and May 2020. From their 5-year pre-COVID-19 medical histories, we extracted multimorbidity features, including drug prescriptions, disease diagnoses, sex, and age. Focusing on COVID-19 hospitalization, we segmented the data into 4 cohorts based on age and sex. Addressing data imbalance through random resampling, we compared various machine learning algorithms to identify the optimal classification model for our evolutionary approach. Using 5-fold cross-validation, we evaluated each model's performance. Our evolutionary algorithm, utilizing a deep learning classifier, generated prediction-based fitness scores to pinpoint multimorbidity combinations associated with COVID-19 hospitalization risk. Eventually, the Apriori algorithm was applied to identify frequent combinations with high support.

RESULTS: We identified multimorbidity predictors associated with COVID-19 hospitalization, indicating more severe COVID-19 outcomes. Frequently occurring morbidity features in the final evolved combinations were age>53, R03BA (glucocorticoid inhalants), and N03AX (other antiepileptics) in cohort 1; A10BA (biguanide or metformin) and N02BE (anilides) in cohort 2; N02AX (other opioids) and M04AA (preparations inhibiting uric acid production) in cohort 3; and G04CA (Alpha-adrenoreceptor antagonists) in cohort 4.

CONCLUSIONS: When combined with other multimorbidity features, even less prevalent medical conditions show associations with the outcome. This study provides insights beyond COVID-19, demonstrating how repurposed administrative data can be adapted and contribute to enhanced risk assessment for vulnerable populations.}, } @article {pmid39022666, year = {2024}, author = {Zheng, C and Chen, JJ and Dai, ZH and Wan, KW and Sun, FH and Huang, JH and Chen, XK}, title = {Physical exercise-related manifestations of long COVID: A systematic review and meta-analysis.}, journal = {Journal of exercise science and fitness}, volume = {22}, number = {4}, pages = {341-349}, pmid = {39022666}, issn = {1728-869X}, abstract = {OBJECTIVE: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors.

METHODS: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis.

RESULTS: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO2max), and anaerobic threshold were impaired in COVID-19 survivors 3 months post-infection compared with non-COVID-19 controls in exercise testing, while VO2 were comparable between the two groups at rest. In contrast, no differences were observed in SpO2, heart rate, blood pressure, fatigue, and dyspnea between COVID-19 survivors and non-COVID-19 controls in exercise testing.

CONCLUSION: The findings suggest an underestimation of the manifestations of PASC. COVID-19 survivors also harbor physical exercise-related symptoms of PASC that can be determined by the exercise testing and are distinct from those observed at rest. Exercise testing should be included while evaluating the symptoms of PASC in COVID-19 survivors.}, } @article {pmid39022434, year = {2024}, author = {Paramita, N and Santoso, DIS and Nusdwinuringtyas, N and Rasmin, M and Kartinah, NT and Jusman, SWA and Abdullah, M and Tinduh, D and Widjanantie, SC and Harini, M and Sianipar, IR and Nugraha, B and Gutenbrunner, C and Widaty, S}, title = {The Delphi Method: Developing a Telerehabilitation Practice Guideline for Patients in Indonesia with Long COVID.}, journal = {International journal of telerehabilitation}, volume = {16}, number = {1}, pages = {e6610}, pmid = {39022434}, issn = {1945-2020}, abstract = {Telerehabilitation has the potential to help expand the reach of rehabilitation intervention. An online questionnaire-based Delphi method set out to develop a telerehabilitation guideline for patients in Indonesia with Long COVID. A Delphi panel comprised of 24 experts was selected from all relevant disciplines. Over two rounds of Delphi testing, panelists gave opinions and indicated their level of agreement with each recommendation. Key elements of consensus for a telerehabilitation guideline for patients with Long COVID includes: the benefit of telerehabilitation, types of rehabilitation intervention needed, methods of intervention, criteria for home-based self-exercise training, set-up of rehabilitation prescription, exercise monitoring, evaluation of rehabilitation intervention and duration of rehabilitation intervention. Further research is needed to determine the feasibility and effectiveness of this guideline.}, } @article {pmid39022343, year = {2024}, author = {Porntharukchareon, T and Dechates, B and Sirisreetreerux, S and Therawit, P and Tawinprai, K}, title = {The existence of adrenal insufficiency in patients with COVID-19 pneumonia.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1337652}, pmid = {39022343}, issn = {1664-2392}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology/blood ; Male ; Middle Aged ; *Adrenal Insufficiency/epidemiology/blood ; Cross-Sectional Studies ; Aged ; *Hydrocortisone/blood ; SARS-CoV-2 ; Adult ; Prevalence ; Adrenocorticotropic Hormone/blood ; }, abstract = {INTRODUCTION: Infection with SARS-CoV-2 virus may result in long COVID, a syndrome characterized by symptoms such as dyspnea, cardiac abnormalities, cognitive impairment, and fatigue. One potential explanation for these symptoms is hypocortisolism.

OBJECTIVE: To evaluate the prevalence of hypocortisolism in patients with a history of COVID-19 pneumonia.

METHODS: Cross-sectional study of patients who were aged ≥18 years and had a 3-month history of radiography-confirmed COVID-19 pneumonia. Exclusion criteria included current or previous treatment with glucocorticoids and use of an oral contraceptive. Adrenal function was evaluated using a low dose (1ug) corticotropin stimulation test (CST). Serum cortisol levels were measured at 0, 30, and 60 minutes, and baseline plasma ACTH was also measured.

RESULTS: Of the 41 patients enrolled, the median age was 62 years, 17 (42%) were female, and all 41 (100%) had severe pneumonia at baseline. Eleven patients (27%) had hypocortisolism, as evidenced by peak cortisol of less than 402.81 nmol/l after low dose (1 µg) CST. Of these 11 patients, 10 (91%) had secondary hypocortisolism (median ACTH 6.27 pmol/L, range 4.98-9.95 pmol/L) and one had primary hypocortisolism (mean ACTH 32.78 pmol/L). Six of the 11 patients with hypocortisolism (54.5%) reported symptoms of persistent fatigue and 5 (45.5%) required regular glucocorticoid replacement.

CONCLUSIONS: Our results suggest that hypocortisolism, predominantly caused by pituitary disruption, may emerge after SARS-CoV-2 infection and should be considered in patients with a history of COVID-19 pneumonia with or without clinical hypocortisolism.}, } @article {pmid39022309, year = {2024}, author = {Lubarsky, D and Clark, DE and Crum, K and Karpinos, A and Austin, ED and Soslow, JH}, title = {Quantifying the impact of post-acute sequelae of coronavirus on the cardiopulmonary endurance of athletes.}, journal = {Pulmonary circulation}, volume = {14}, number = {3}, pages = {e12413}, pmid = {39022309}, issn = {2045-8932}, abstract = {Post-acute sequelae of Coronavirus (PASC), or Long COVID, has emerged as a critical health concern. The clinical manifestations of PASC have been described, but studies have not quantified the cardiopulmonary effects. The goal of this study was to quantify PASC cardiopulmonary changes among endurance athletes. Endurance athletes were recruited via social media; 45 met inclusion criteria, 32 had PASC and 13 were asymptomatic at 3 months (control). Comprehensive interviews were conducted to assess: cardiopulmonary symptoms at 3 months; quantitative and qualitative changes in cardiovascular endurance; exercise hours per week at baseline and 3 months; and Modified Oslo, Dyspnea, and EQ-5D-5L scales. All collected data was based on self-reported symptoms. Wilcoxon rank sum compared PASC with control to distinguish the effects of PASC vs effects of COVID infection/lockdown. PASC subjects were more likely to be female (Table). The most common 3-month symptoms in PASC were fatigue and shortness of breath. Based on self-reported data, subjects endorsed a median decrease of 27% in cardiopulmonary endurance levels compared with 0% in controls (p = 0.0019). PASC subjects exercised less hours and had worse self-reported health as compared with controls. PASC subjects also had significantly worse Modified Oslo, Dyspnea, and EQ-5D-5L scores. Of the 32 PASC patients, 10 (31%) reported a complete inability to engage in any cardiovascular endurance exercise at 3 months. PASC leads to a significant, quantifiable decrease in cardiopulmonary health and endurance.}, } @article {pmid39019602, year = {2024}, author = {Tokumasu, K and Matsuki, N and Fujikawa, H and Sakamoto, Y and Otsuka, F}, title = {Reliability and Validity of the Japanese Version of the Fatigue Assessment Scale.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.4101-24}, pmid = {39019602}, issn = {1349-7235}, abstract = {Objective General fatigue is one of the most frequent chief complaints in primary care, and an accurate assessment of fatigue has a direct impact on a patient's quality of life and treatment decisions. The Fatigue Assessment Scale (FAS), a measure of general fatigue, is useful for assessing fatigue in diverse cultures and diseases. However, there has been no study showing the reliability and validity of the scale in the Japanese context. The present study assessed the reliability and validity of the Japanese version of the FAS. Methods This study was conducted on 649 patients with long COVID who had a high frequency of general fatigue. To test the structural validity of the FAS, the patients were randomly divided into two groups: one in which an exploratory factor analysis (EFA) was conducted and one in which a confirmatory factor analysis (CFA) was conducted. Cronbach's alpha was calculated to assess internal consistency reliability. Results As 58 patients had missing values, we analyzed the data of 591 patients. The EFA led to an FAS comprising two factors. The CFA showed an acceptable fit for this two-factor model. The internal consistency was found to be good (Cronbach's alpha =0.89). Conclusion This study verified the structural validity and internal consistency and reliability of the Japanese version of the FAS. The results indicate that the Japanese version of the FAS is useful for assessing general fatigue in patients with long COVID in Japan.}, } @article {pmid39019092, year = {2024}, author = {Jeon, D and Kim, SH and Kim, J and Jeong, H and Uhm, C and Oh, H and Cho, K and Cho, Y and Park, IH and Oh, J and Kim, JJ and Hwang, JY and Lee, HJ and Lee, HY and Seo, JY and Shin, JS and Seong, JK and Nam, KT}, title = {Discovery of a new long COVID mouse model via systemic histopathological comparison of SARS-CoV-2 intranasal and inhalation infection.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {7}, pages = {167347}, doi = {10.1016/j.bbadis.2024.167347}, pmid = {39019092}, issn = {1879-260X}, mesh = {Animals ; *COVID-19/pathology/virology ; *SARS-CoV-2 ; Mice ; *Disease Models, Animal ; *Lung/pathology/virology ; Angiotensin-Converting Enzyme 2/metabolism/genetics ; Olfactory Bulb/pathology/virology ; Humans ; Administration, Intranasal ; Female ; Olfactory Receptor Neurons/virology/metabolism ; }, abstract = {Intranasal infection is commonly used to establish a SARS-CoV-2 mouse model due to its non-invasive procedures and a minimal effect from the operation itself. However, mice intranasally infected with SARS-CoV-2 have a high mortality rate, which limits the utility of this model for exploring therapeutic strategies and the sequelae of non-fatal COVID-19 cases. To resolve these limitations, an aerosolised viral administration method has been suggested. However, an in-depth pathological analysis comparing the two models is lacking. Here, we show that inhalation and intranasal SARS-CoV-2 (10[6] PFU) infection models established in K18-hACE2 mice develop unique pathological features in both the respiratory and central nervous systems, which could be directly attributed to the infection method. While the inhalation-infection model exhibited relatively milder pathological parameters, it closely mimicked the prevalent chest CT pattern observed in COVID-19 patients with focal, peripheral lesions and fibrotic scarring in the recuperating lung. We also found the evidence of direct neuron-invasion from the olfactory receptor neurons to the olfactory bulb in the intranasal model and showed the trigeminal nerve as an alternative route of transmission to the brain in inhalation infected mice. Even after viral clearance confirmed at 14 days post-infection, mild lesions were still found in the brain of inhalation-infected mice. These findings suggest that the inhalation-infection model has advantages over the intranasal-infection model in closely mimicking the pathological features of non-fatal symptoms of COVID-19, demonstrating its potential to study the sequelae and possible interventions for long COVID.}, } @article {pmid39018529, year = {2024}, author = {Rosen, CJ}, title = {Viral Variants, Vaccinations, and Long Covid - New Insights.}, journal = {The New England journal of medicine}, volume = {391}, number = {6}, pages = {561-562}, doi = {10.1056/NEJMe2407575}, pmid = {39018529}, issn = {1533-4406}, mesh = {Humans ; *COVID-19/complications/immunology/prevention & control/virology ; *COVID-19 Vaccines/administration & dosage ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention & control/virology ; *SARS-CoV-2/genetics/immunology/pathogenicity ; Vaccination ; Pandemics/prevention & control ; Incidence ; }, } @article {pmid39018475, year = {2024}, author = {Buonsenso, D and Sorrentino, S and Ferretti, A and Morello, R and Valentini, P and Di Gennaro, L and De Candia, E}, title = {Circulating Activated Platelets in Children With Long Covid: A Case-Controlled Preliminary Observation.}, journal = {The Pediatric infectious disease journal}, volume = {43}, number = {12}, pages = {e430-3}, pmid = {39018475}, issn = {1532-0987}, abstract = {We investigated if children with Long Covid (n=14) have activated platelets compared with healthy controls (n=14). Platelet activation and secretion markers were investigated by flow cytometry using MoAbs directed against P-selectin, CD63, and PAC-1 in quiescent platelets and in platelets stimulated with 10-µM adenosine diphosphate and 25-µM protease activated receptor 1-activating peptide. Circulating platelets of patients with Long Covid had significantly increased expression of the activation marker cytometry using MoAbs directed against P-selectin (P = 0.019).}, } @article {pmid39016279, year = {2024}, author = {Stufano, A and Lucchese, G and Schino, V and Plantone, D and de Maria, L and Vimercati, L and Floel, A and Iavicoli, I and Lovreglio, P}, title = {Psychological General Well-being, Cognitive Failure, and Inflammation Biomarkers Among Workers 4 Months After a Mild/Asymptomatic SARS-CoV-2 Infection.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {10}, pages = {793-802}, doi = {10.1097/JOM.0000000000003174}, pmid = {39016279}, issn = {1536-5948}, mesh = {Humans ; *COVID-19/psychology ; Male ; Cross-Sectional Studies ; *Biomarkers/blood ; Adult ; *Cognitive Dysfunction/blood/diagnosis ; Middle Aged ; *Inflammation/blood ; Female ; *SARS-CoV-2 ; Depression ; }, abstract = {OBJECTIVE: To investigate the relationship between cognitive complaints, systemic inflammatory biomarkers, and psychological general well-being (PGWB) after mild/asymptomatic SARS-CoV-2 infection, according to the presence of long COVID and work tasks.

METHODS: University employees and metal workers were recruited in a cross-sectional study 4 months after SARS-CoV-2 infection to assess cognitive impairment, individual PGWB index, inflammatory biomarkers, namely platelet-lymphocyte, neutrophil-lymphocyte, and lymphocyte-monocyte ratios, and the presence of long COVID symptoms.

RESULTS: A significant increase in the levels of inflammatory biomarkers was observed in subjects with long COVID. Furthermore, the PGWB index was influenced by long COVID symptoms and subjective cognitive and depressive symptoms, but not by work activity.

CONCLUSIONS: In occupational settings, it is crucial to detect the presence of long COVID symptoms and systemic inflammation early, as they may be associated with lower PGWB.}, } @article {pmid39014958, year = {2024}, author = {Shen, Z and Li, Q and Wu, J and Zhu, D and Bai, J and Ren, R and Zhang, J and Li, Y and Wang, M and Gu, J and Li, Y and Dong, W and Wang, H and Sun, T and Yang, F and Zhou, X and Yang, J and Tarimo, CS and Ma, M and Feng, Y and Miao, Y}, title = {Dynamic evolution of COVID-19 vaccine hesitancy over 2021-2023 among Chinese population: Repeated nationwide cross-sectional study.}, journal = {Journal of medical virology}, volume = {96}, number = {7}, pages = {e29800}, doi = {10.1002/jmv.29800}, pmid = {39014958}, issn = {1096-9071}, support = {//National Social Science Fund of China/ ; //Collaborative Innovation Key Project of Zhengzhou/ ; }, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology ; *COVID-19/prevention & control/epidemiology ; *COVID-19 Vaccines/administration & dosage ; Cross-Sectional Studies ; East Asian People ; Surveys and Questionnaires ; Vaccination/psychology/statistics & numerical data ; *Vaccination Hesitancy/statistics & numerical data/psychology ; }, abstract = {Globally, the rollout of COVID-19 vaccine had been faced with a significant barrier in the form of vaccine hesitancy. This study adopts a multi-stage perspective to explore the prevalence and determinants of COVID-19 vaccine hesitancy, focusing on their dynamic evolutionary features. Guided by the integrated framework of the 3Cs model (complacency, confidence, and convenience) and the EAH model (environmental, agent, and host), this study conducted three repeated national cross-sectional surveys. These surveys carried out from July 2021 to February 2023 across mainland China, targeted individuals aged 18 and older. They were strategically timed to coincide with three critical vaccination phases: universal coverage (stage 1), partial coverage (stage 2), and key population coverage (stage 3). From 2021 to 2023, the surveys examined sample sizes of 29 925, 6659, and 5407, respectively. The COVID-19 vaccine hesitation rates increased from 8.39% in 2021 to 29.72% in 2023. Urban residency, chronic condition, and low trust in vaccine developer contributed to significant COVID-19 vaccine hesitancy across the pandemic. Negative correlations between the intensity of vaccination policies and vaccine hesitancy, and positive correlations between vaccine hesitancy and long COVID, were confirmed. This study provides insights for designing future effective vaccination programs for emerging vaccine-preventable infectious X diseases.}, } @article {pmid39012668, year = {2024}, author = {Villacampa, A and Shamoon, L and Valencia, I and Morales, C and Figueiras, S and de la Cuesta, F and Sánchez-Niño, D and Díaz-Araya, G and Sánchez-Pérez, I and Lorenzo, Ó and Sánchez-Ferrer, CF and Peiró, C}, title = {SARS-CoV-2 S Protein Reduces Cytoprotective Defenses and Promotes Human Endothelial Cell Senescence.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.0405}, pmid = {39012668}, issn = {2152-5250}, abstract = {Premature vascular aging and endothelial cell senescence are major risk factors for cardiovascular diseases and atherothrombotic disturbances, which are main complications of both acute and long COVID-19. The S protein of SARS-CoV2, which acts as the receptor binding protein for the viral infection, is able to induce endothelial cells inflammation and it has been found as an isolated element in the circulation and in human tissues reservoirs months after infection. Here, we investigated whether the S protein is able to directly induce endothelial cell senescence and deciphered some of the mechanisms involved. In primary cultures of human umbilical vein endothelial cells (HUVEC), SARS-CoV-2 S protein enhanced in a concentration-dependent manner the cellular content of senescence and DNA damage response markers (senescence-associated-β galactosidase, γH2AX), as well as growth-arrest effectors (p53, p21, p16). In parallel, the S protein reduced the availability of cytoprotective proteins, such as the anti-aging protein klotho, Nrf2 or heme oxygenase-1, and caused functional harm by impairing ex vivo endothelial-dependent vasorelaxation in murine microvessels. These effects were prevented by the pharmacological inhibition of the NLRP3 inflammasome with MCC950. Furthermore, the supplementation with either recombinant klotho or angiotensin-(1-7), equally protected against the pro-senescence, pro-inflammatory and pro-oxidant action of the S protein. Globally, this study proposes novel mechanisms of disease in the context of COVID-19 and its vascular sequelae and provides pharmacological clues in order to prevent such complications.}, } @article {pmid39012495, year = {2024}, author = {Elmer, N and Reißhauer, A and Brehm, K and Drebinger, D and Schaller, SJ and Schwedtke, C and Liebl, ME}, title = {Functional outcome after interdisciplinary, acute rehabilitation in COVID-19 patients: a retrospective study.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1993-2001}, pmid = {39012495}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/rehabilitation ; Male ; Retrospective Studies ; Female ; Middle Aged ; Aged ; *Activities of Daily Living ; Adult ; Treatment Outcome ; Recovery of Function/physiology ; Aged, 80 and over ; }, abstract = {BACKGROUND: Survivors of severe COVID-19 often exhibit a variety of sequelae including loss of mobility and ADL (activities of daily living) capacity. Acute rehabilitation (AR) is an interdisciplinary rehabilitation intervention applied early while still in a hospital setting. The goal of AR is to improve functional limitations and to increase functional independence at discharge. It is established in the treatment of patients with other severe diseases such as sepsis, polytrauma, or stroke. Data concerning AR in COVID-19 are sparse.

AIM: To evaluate the changes in physical function during AR in patients after severe COVID-19.

METHODS: This monocentric, retrospective observational study examined the functional outcomes of a sample of COVID-19-patients who received interdisciplinary AR at a university hospital. Inclusion criteria were a positive SARS-CoV-2 test in 05/2020-01/2022 and transfer to AR after intensive care treatment. 87 patients were elegible for evaluation, 3 of whom were excluded because of death during AR. Data were extracted from the hospital information system. In a pre-post analysis, mobility (Charité Mobility Index), ADL (Barthel Index), and oxygen demand were assessed. In addition, discharge location after AR, factors associated with AR unit length of stay, and functional improvements were analyzed.

RESULTS: Data of 84 patients were analyzed. Mobility increased significantly from a median of 4 [1.25-6] CHARMI points at admission to a median of 9 [8.25-9] at discharge (p < 0.001). ADL increased significantly from a median of 52.5 [35.0-68.75] Barthel Index points at admission to a median of 92.5 [85-95] at discharge (p < 0.001). Oxygen demand decreased from 80.7 to 30.5% of patients. The majority (55.9%) of patients were discharged home, while 36.9% received direct follow-up rehabilitation. Older age correlated significantly with lower scores on the discharge assessment for mobility (Spearman's ϱ = -0.285, p = 0.009) and ADL (Spearman's ϱ = -0.297, p = 0.006).

CONCLUSION: Acute rehabilitation is a viable option for COVID-19 patients with severe functional deficits after ICU treatment to achieve functional progress in mobility and ADL, reduce oxygen requirements and enable follow-up rehabilitation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: Trial registration number: DRKS00025239. Date of registration: 08 Sep 2021.}, } @article {pmid39011957, year = {2024}, author = {Agrawal, P and Giron, LB and Singh, S and Haw, NJ and Goldman, AR and Elkaeid, M and Macatangay, B and Palella, FJ and Alcaide, ML and Moran, CA and Kassaye, SG and Erdmann, N and Chew, KW and Floris-Moore, M and Chandran, A and Augenbraun, MH and Sharma, A and Palmer, C and Landay, AL and Peluso, MJ and Keshavarzian, A and Brown, TT and Tien, PC and Abdel-Mohsen, M}, title = {Prepandemic Metabolic Correlates of Coronavirus Disease 2019 (COVID-19) Severity and Long COVID Incidence in People Living With HIV.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {4}, pages = {912-918}, doi = {10.1093/infdis/jiae362}, pmid = {39011957}, issn = {1537-6613}, support = {R01AA029859/GF/NIH HHS/United States ; 1UM1Al126620//to Cure HIV-1 Infection by Combination Immunotherapy/ ; P30 AI 045008 to//Penn Center for AIDS Research/ ; //TUHS Auxiliary Endowment for Excellence/ ; //BEAT-HIV Martin Delaney Collaboratory/ ; U01 HL146202/HL/NHLBI NIH HHS/United States ; //American Lung Association/ ; //at TNRPC/ ; }, mesh = {Humans ; *COVID-19/metabolism/complications/epidemiology ; *HIV Infections/complications ; Male ; Incidence ; Female ; Middle Aged ; *Severity of Illness Index ; *SARS-CoV-2 ; Tryptophan/metabolism ; Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Host metabolic dysregulation, especially in tryptophan metabolism, is intricately linked to coronavirus disease 2019 (COVID-19) severity and its postacute sequelae (long COVID). People living with human immunodeficiency virus (HIV; PLWH) experience similar metabolic dysregulation and face an increased risk of developing long COVID. However, whether preexisting HIV-associated metabolic dysregulations contribute in predisposing PLWH to severe COVID-19 outcomes remains underexplored. Analyzing prepandemic samples from PLWH with documented postinfection outcomes, we found specific metabolic alterations, including increased tryptophan catabolism, predicting an elevated risk of severe COVID-19 and the incidence of long COVID. These alterations warrant further investigation for their potential prognostic and mechanistic significance in determining COVID-19 complications.}, } @article {pmid39011859, year = {2024}, author = {Zelek, WM}, title = {Is Long COVID a Complement Dysregulation Disease?.}, journal = {Clinical chemistry}, volume = {70}, number = {12}, pages = {1398-1401}, doi = {10.1093/clinchem/hvae088}, pmid = {39011859}, issn = {1530-8561}, } @article {pmid39009459, year = {2024}, author = {Sinha, K and Gutacker, N and Gu, Y and Haagsma, J and Kumar, K and Aghdaee, M}, title = {Protocol for a longitudinal study examining the trajectory of COVID-19, post-COVID, multidimensional disadvantage and health-related quality of life in India: the IndiQol Project.}, journal = {BMJ open}, volume = {14}, number = {7}, pages = {e080985}, pmid = {39009459}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; India/epidemiology ; *Quality of Life ; Longitudinal Studies ; *SARS-CoV-2 ; Adult ; Research Design ; Male ; Female ; Vulnerable Populations ; Pandemics ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has raised concerns about the persistence of symptoms after infection, commonly referred to as 'post-COVID' or 'long-COVID'. While countries in high-resource countries have highlighted the increased risk of disadvantaged communities, there is limited understanding of how COVID-19 and post-COVID conditions affect marginalised populations in low-income and middle-income countries. We study the longitudinal patterns of COVID-19, post-COVID symptoms and their impact on the health-related quality of life through the IndiQol Project.

METHODS AND ANALYSIS: The IndiQol Project conducts household surveys across India to collect data on the incidence of COVID-19 and multidimensional well-being using a longitudinal design. We select a representative sample across six states surveyed over four waves. A two-stage sampling design was used to randomly select primary sampling units in rural and urban areas of each State. Using power analysis, we select an initial sample of 3000 household and survey all adult household members in each wave. The survey data will be analysed using limited dependent variable models and matching techniques to provide insights into the impact of COVID-19 pandemic and post-COVID on health and well-being of individuals in India.

ETHICS AND DISSEMINATION: Ethics approval for the IndiQol Project was obtained from the Macquarie University Human Research Ethics Committee in Sydney, Australia and Institutional Review Board of Morsel in India. The project results will be published in peer-reviewed journals. Data collected from the IndiQol project will be deposited with the EuroQol group and will be available to use by eligible researchers on approval of request.}, } @article {pmid39008486, year = {2024}, author = {Wynberg, E and Han, AX and van Willigen, HDG and Verveen, A and van Pul, L and Maurer, I and van Leeuwen, EM and van den Aardweg, JG and de Jong, MD and Nieuwkerk, P and Prins, M and Kootstra, NA and de Bree, GJ and , }, title = {Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0304990}, pmid = {39008486}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/blood/immunology/epidemiology ; Female ; Male ; Middle Aged ; Prospective Studies ; *Cytokines/blood ; *SARS-CoV-2/isolation & purification ; Adult ; Inflammation/blood ; Netherlands/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BACKGROUND: After initial COVID-19, immune dysregulation may persist and drive post-acute sequelae of COVID-19 (PASC). We described longitudinal trajectories of cytokines in adults up to 6 months following SARS-CoV-2 infection and explored early predictors of PASC.

METHODS: RECoVERED is a prospective cohort of individuals with laboratory-confirmed SARS-CoV-2 infection between May 2020 and June 2021 in Amsterdam, the Netherlands. Serum was collected at weeks 4, 12 and 24 of follow-up. Monthly symptom questionnaires were completed from month 2 after COVID-19 onset onwards; lung diffusion capacity (DLCO) was tested at 6 months. Cytokine concentrations were analysed by human magnetic Luminex screening assay. We used a linear mixed-effects model to study log-concentrations of cytokines over time, assessing their association with socio-demographic and clinical characteristics that were included in the model as fixed effects.

RESULTS: 186/349 (53%) participants had ≥2 serum samples and were included in current analyses. Of these, 101/186 (54%: 45/101[45%] female, median age 55 years [IQR = 45-64]) reported PASC at 12 and 24 weeks after COVID-19 onset. We included 37 reference samples (17/37[46%] female, median age 49 years [IQR = 40-56]). In a multivariate model, PASC was associated with raised CRP and abnormal diffusion capacity with raised IL10, IL17, IL6, IP10 and TNFα at 24 weeks. Early (0-4 week) IL-1β and BMI at COVID-19 onset were predictive of PASC at 24 weeks.

CONCLUSIONS: Our findings indicate that immune dysregulation plays an important role in PASC pathogenesis, especially among individuals with reduced pulmonary function. Early IL-1β shows promise as a predictor of PASC.}, } @article {pmid39006446, year = {2024}, author = {Haddad, NS and Morrison-Porter, A and Quehl, H and Capric, V and Lamothe, PA and Anam, F and Runnstrom, MC and Truong, AD and Dixit, AN and Woodruff, MC and Chen, A and Park, J and Nguyen, DC and Hentenaar, I and Kim, CY and Kyu, S and Stewart, B and Wagman, E and Geoffroy, H and Sanz, D and Cashman, KS and Ramonell, RP and Cabrera-Mora, M and Alter, DN and Roback, JD and Horwath, MC and O'Keefe, JB and Dretler, AW and Gripaldo, R and Yeligar, SM and Natoli, T and Betin, V and Patel, R and Vela, K and Hernandez, MR and Usman, S and Varghese, J and Jalal, A and Lee, S and Le, SN and Amoss, RT and Daiss, JL and Sanz, I and Lee, FE}, title = {MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39006446}, support = {T32 HL116271/HL/NHLBI NIH HHS/United States ; U19 AI109962/AI/NIAID NIH HHS/United States ; R01 AI172254/AI/NIAID NIH HHS/United States ; R01 AI121252/AI/NIAID NIH HHS/United States ; T32 GM095442/GM/NIGMS NIH HHS/United States ; P01 AI125180/AI/NIAID NIH HHS/United States ; T32 AI074492/AI/NIAID NIH HHS/United States ; U01 AI045969/AI/NIAID NIH HHS/United States ; U54 CA260563/CA/NCI NIH HHS/United States ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present. It is also positive after vaccination when spike proteins elicit an acute immune response. Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflammation only in PASC. Additionally, in PASC patients, MENSAs are also positive for Epstein-Barr Virus (EBV) in 37%, Human Cytomegalovirus (CMV) in 23%, and herpes simplex virus 2 (HSV2) in 15% compared to 17%, 4%, and 4% in CR controls respectively. Combined, a total of 60% of PASC patients have a positive MENSA for SARS2, EBV, CMV, and/or HSV2. MENSA offers a unique antibody snapshot to reveal the underlying viral drivers in long-COVID thus demonstrating the persistence of SARS2 and reactivation of viral herpes in 60% of PASC patients.}, } @article {pmid39006431, year = {2024}, author = {Pietzner, M and Denaxas, S and Yasmeen, S and Ulmer, MA and Nakanishi, T and Arnold, M and Kastenmüller, G and Hemingway, H and Langenberg, C}, title = {Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39006431}, support = {U19 AG074879/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; R01 AG081322/AG/NIA NIH HHS/United States ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; R01 AG069901/AG/NIA NIH HHS/United States ; }, abstract = {Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses, including common, but non-fatal diseases are scarce, but may help to understand severe COVID-19 among patients at supposedly low risk. Here, we systematically harmonized >12 million primary care and hospitalisation health records from ~500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID. We identified a total of 679 diseases associated with an increased risk for severe COVID-19 (n=672) and/or Long COVID (n=72) that spanned almost all clinical specialties and were strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we established consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This included a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observed partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis (e.g., MUC5B, NPNT, and PSMD3) or rheumatoid arthritis (e.g., TYK2), possibly indicating a segregation of disease mechanisms. Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple - including non-fatal - conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.}, } @article {pmid39006428, year = {2024}, author = {Herbert, C and Antar, AAR and Broach, J and Wright, C and Stamegna, P and Luzuriaga, K and Hafer, N and McManus, DD and Manabe, YC and Soni, A}, title = {Relationship between acute SARS-CoV-2 viral clearance with Long COVID Symptoms: a cohort study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39006428}, support = {TL1 TR001454/TR/NCATS NIH HHS/United States ; U54 HL143541/HL/NHLBI NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: The relationship between SARS-CoV-2 viral dynamics during acute infection and the development of long COVID is largely unknown.

METHODS: A total of 7361 asymptomatic community-dwelling people enrolled in the Test Us at Home parent study between October 2021 and February 2022. Participants self-collected anterior nasal swabs for SARS-CoV-2 RT-PCR testing every 24-48 hours for 10-14 days, regardless of symptom or infection status. Participants who had no history of COVID-19 at enrollment and who were subsequently found to have ≥1 positive SARS-CoV-2 RT-PCR test during the parent study were recontacted in August 2023 and asked whether they had experienced long COVID, defined as the development of new symptoms lasting 3 months or longer following SARS-CoV-2 infection. Participant's cycle threshold values were converted into viral loads, and slopes of viral clearance were modeled using post-nadir viral loads. Using a log binomial model with the modeled slopes as the exposure, we calculated the relative risk of subsequently developing long COVID with 1-2 symptoms, 3-4 symptoms, or 5+ symptoms, adjusting for age, number of symptoms, and SARS-CoV-2 variant. Adjusted relative risk (aRR) of individual long COVID symptoms based on viral clearance was also calculated.

RESULTS: 172 participants were eligible for analyses, and 59 (34.3%) reported experiencing long COVID. The risk of long COVID with 3-4 symptoms and 5+ symptoms increased by 2.44 times (aRR: 2.44; 95% CI: 0.88-6.82) and 4.97 times (aRR: 4.97; 95% CI: 1.90-13.0) per viral load slope-unit increase, respectively. Participants who developed long COVID had significantly longer times from peak viral load to viral clearance during acute disease than those who never developed long COVID (8.65 [95% CI: 8.28-9.01] vs. 10.0 [95% CI: 9.25-10.8]). The slope of viral clearance was significantly positively associated with long COVID symptoms of fatigue (aRR: 2.86; 95% CI: 1.22-6.69), brain fog (aRR: 4.94; 95% CI: 2.21-11.0), shortness of breath (aRR: 5.05; 95% CI: 1.24-20.6), and gastrointestinal symptoms (aRR: 5.46; 95% CI: 1.54-19.3).

DISCUSSION: We observed that longer time from peak viral load to viral RNA clearance during acute COVID-19 was associated with an increased risk of developing long COVID. Further, slower clearance rates were associated with greater number of symptoms of long COVID. These findings suggest that early viral-host dynamics are mechanistically important in the subsequent development of long COVID.}, } @article {pmid39005628, year = {2024}, author = {Feng, J and Chen, J and Li, X and Ren, X and Chen, J and Li, Z and Wu, Y and Zhang, Z and Yang, R and Li, J and Lu, Y and Liu, Y}, title = {Mendelian randomization and Bayesian model averaging of autoimmune diseases and Long COVID.}, journal = {Frontiers in genetics}, volume = {15}, number = {}, pages = {1383162}, pmid = {39005628}, issn = {1664-8021}, abstract = {BACKGROUND: Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.

METHODS: Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn's disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).

RESULTS: The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00-1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01-1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03-1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.

CONCLUSION: This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.}, } @article {pmid39003005, year = {2024}, author = {Broussard, CA and Azola, A and Rowe, PC}, title = {Post-Acute Sequelae of SARS-CoV-2 Infection and Its Impact on Adolescents and Young Adults.}, journal = {Pediatric clinics of North America}, volume = {71}, number = {4}, pages = {613-630}, doi = {10.1016/j.pcl.2024.04.004}, pmid = {39003005}, issn = {1557-8240}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Adolescent ; Young Adult ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {This review discusses the varying definitions for post-acute sequelae of SARS CoV-2 infection (PASC) in adolescents and young adults (AYAs), symptom profiles of AYAs with PASC, and assessment and management strategies when AYAs present with symptoms concerning for PASC. Additionally, it reviews the impact that PASC can have on AYAs and includes strategies for providers to support AYAs with PASC. Finally, it concludes with a discussion around equity in the care of AYAs with possible PASC.}, } @article {pmid39002665, year = {2024}, author = {Sun, G and Lin, K and Ai, J and Zhang, W}, title = {The efficacy of antivirals, corticosteroids, and monoclonal antibodies as acute COVID-19 treatments in reducing the incidence of long COVID: a systematic review and meta-analysis.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {12}, pages = {1505-1513}, doi = {10.1016/j.cmi.2024.07.006}, pmid = {39002665}, issn = {1469-0691}, mesh = {Aged ; Female ; Humans ; Male ; *Adrenal Cortex Hormones/therapeutic use ; *Antibodies, Monoclonal/therapeutic use ; *Antiviral Agents/therapeutic use ; *COVID-19/complications/immunology/virology ; *COVID-19 Drug Treatment/methods ; Incidence ; *Post-Acute COVID-19 Syndrome/epidemiology/immunology/prevention & control/virology ; SARS-CoV-2/immunology ; Treatment Outcome ; }, abstract = {BACKGROUND: Whether treatment during acute COVID-19 results in protective efficacy against long COVID incidence remains unclear.

OBJECTIVES: To assess the relationship between acute COVID-19 treatments of antivirals, corticosteroids, and monoclonal antibodies (mAbs) and long COVID incidence, and their effects in different populations and individual symptoms.

METHODS: A systematic review and meta-analysis.

DATA SOURCES: Searches were conducted up to January 29, 2024 in PubMed, Medline, Web of Science, and Embase.

STUDY ELIGIBILITY CRITERIA: Articles that reported long COVID incidence post-acute COVID with a follow-up of at least 30 days with no language restrictions.

PARTICIPANTS: Patients with a COVID-19 diagnosis history.

INTERVENTIONS: Patients treated with antivirals, corticosteroids or mAbs.

ASSESSMENT OF RISK OF BIAS: Quality assessment was based on the Newcastle-Ottawa scale, risk of bias in nonrandomized studies of interventions-I and Cochrane risk of bias tool.

METHODS OF DATA SYNTHESIS: Basic characteristics were documented for each study. Random forest model and meta-regression were used to evaluate the correlation between treatments and long COVID.

RESULTS: Our search identified 2363 records, 32 of which were included in the qualitative synthesis and 25 included into the meta-analysis. Effect size from 14 papers investigating acute COVID-19 antiviral treatment concluded its protective efficacy against long COVID (OR, 0.61; 95% CI, 0.48-0.79; p 0.0002); however, corticosteroid (OR, 1.57; 95% CI, 0.80-3.09; p 0.1913), and mAbs treatments (OR, 0.94; 95% CI, 0.56-1.56; p 0.8012) did not generate such effect. Subsequent subgroup analysis revealed that antivirals provided stronger protection in the aged, male, unvaccinated and nondiabetic populations. Furthermore, antivirals effectively reduced 8 out of the 22 analysed long COVID symptoms.

CONCLUSIONS: Our meta-analysis determined that antivirals reduced long COVID incidence across populations and should thus be recommended for acute COVID-19 treatment. There was no relationship between mAbs treatment and long COVID, but studies should be conducted to clarify acute COVID-19 corticosteroids' potential harmful effects on the post-acute phase of COVID-19.}, } @article {pmid39000027, year = {2024}, author = {Currie, C and Myklebust, TÅ and Bjerknes, C and Framroze, B}, title = {Assessing the Potential of an Enzymatically Liberated Salmon Oil to Support Immune Health Recovery from Acute SARS-CoV-2 Infection via Change in the Expression of Cytokine, Chemokine and Interferon-Related Genes.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000027}, issn = {1422-0067}, support = {20CCHH/OP110921//Hofseth BioCare/ ; }, mesh = {Humans ; *Fish Oils/pharmacology/therapeutic use ; *COVID-19/immunology/virology ; Male ; *Interferons/metabolism/genetics ; *SARS-CoV-2/immunology ; *Cytokines/metabolism ; Female ; Middle Aged ; *Chemokines/metabolism/genetics ; Adult ; COVID-19 Drug Treatment ; Fatty Acids, Omega-3/pharmacology ; }, abstract = {Cytokines, chemokines, and interferons are released in response to viral infection with the ultimate aim of viral clearance. However, in SARS-CoV-2 infection, there is an imbalanced immune response, with raised cytokine levels but only a limited interferon response with inefficient viral clearance. Furthermore, the inflammatory response can be exaggerated, which risks both acute and chronic sequelae. Several observational studies have suggested a reduced risk of progression to severe COVID-19 in subjects with a higher omega-3 index. However, randomized studies of omega-3 supplementation have failed to replicate this benefit. Omega-3 fats provide important anti-inflammatory effects; however, fatty fish contains many other fatty acids that provide health benefits distinct from omega-3. Therefore, the immune health benefit of whole salmon oil (SO) was assessed in adults with mild to moderate COVID-19. Eleven subjects were randomized to best supportive care (BSC) with or without a full spectrum, enzymatically liberated SO, dosed at 4g daily, for twenty-eight days. Nasal swabs were taken to measure the change in gene expression of markers of immune response and showed that the SO provided both broad inflammation-resolving effects and improved interferon response. The results also suggest improved lung barrier function and enhanced immune memory, although the clinical relevance needs to be assessed in longer-duration studies. In conclusion, the salmon oil was well tolerated and provided broad inflammation-resolving effects, indicating a potential to enhance immune health.}, } @article {pmid38999517, year = {2024}, author = {Roland, A and Staring, L and Van Puyvelde, M and McGlone, F and Mairesse, O}, title = {Sleep, Mental Health, and the Need for Physical and Real-Life Social Contact with (Non-)Family Members during the COVID-19 Pandemic: A Bayesian Network Analysis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {13}, pages = {}, pmid = {38999517}, issn = {2077-0383}, support = {11N8923N//Fonds Wetenschappelijk Onderzoek/ ; 11M0123N//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {Background/Objectives: The forced social isolation implemented to prevent the spread of the COVID-19 virus was accompanied by a worsening of mental health, an increase in insomnia symptoms, and the emergence of 'skin hunger'-an increased longing for personal touch. This study aimed to enhance our understanding of the interconnection between sleep, mental health, and the need for physical (NPC) and real-life social contact (NRL-SC). Methods: A total of 2827 adults participated in an online survey during the second COVID-19 lockdown. A Bayesian Gaussian copula graphical model (BGCGM) and a Bayesian-directed acyclic graph (DAG) were estimated, and mixed ANOVAs were carried out. Results: NPC with non-family members (t(2091) = 12.55, p < 0.001, d = 0.27) and relational lifestyle satisfaction (t(2089) = 13.62, p < 0.001, d = 0.30) were lower during the second lockdown than before the pandemic. In our BGCGM, there were weak positive edges between the need for PC and RL-SC on one hand and sleep and mental health on the other. Conclusions: During the second lockdown, people craved less physical contact with non-family members and were less satisfied with their relational lifestyle than before the pandemic. Individuals with a greater need for PC and RL-SC reported poorer mental health (i.e., worry, depression, and mental fatigue).}, } @article {pmid38999375, year = {2024}, author = {Matsuda, Y and Sakurada, Y and Otsuka, Y and Tokumasu, K and Nakano, Y and Sunada, N and Honda, H and Hasegawa, T and Takase, R and Omura, D and Ueda, K and Otsuka, F}, title = {Changes in Working Situations of Employed Long COVID Patients: Retrospective Study in Japanese Outpatient Clinic.}, journal = {Journal of clinical medicine}, volume = {13}, number = {13}, pages = {}, pmid = {38999375}, issn = {2077-0383}, support = {23fk0108585h0001//Japan Agency for Medical Research and Development/ ; }, abstract = {Purpose: The present study aimed to uncover the impact of long COVID on the working situations of Japanese patients. Methods: Changes in the working situations of the patients who visited our long COVID clinic were evaluated from medical records for the aspects of physical status, quality of life (QOL), and mental conditions. Results: Of 846 long COVID patients who visited our clinic from February 2021 to December 2023, 545 employed patients aged between 18 and 65 years were included in this study. A total of 295 patients (54.1%) with long COVID (median age: 43 years, female: 55.6%) experienced changes in their working status. Those patients included 220 patients (40.4%) who took a leave of absence, 53 patients (9.7%) who retired, and 22 patients (4%) with reduced working hours. Most of the patients (93.2%) with changes in working conditions had mild disease severity in the acute phase of COVID-19. The majority of those patients with mild disease severity (58.8%) were infected in the Omicron-variant phase and included 65.3% of the female patients. The major symptoms in long COVID patients who had changes in their working situations were fatigue, insomnia, headache, and dyspnea. Scores indicating fatigue and QOL were worsened in long COVID patients who had changes in their working situations. In addition, 63.7% of the long COVID patients with changes in their working situations had decreases in their incomes. Conclusions: Changes in the working situation of long COVID patients who were employed had a negative impact on the maintenance of their QOL.}, } @article {pmid38996944, year = {2024}, author = {Loo, C and Treacy, MG and Toerien, L and Msellati, A and Catanzano, T}, title = {Emergency Presentations of Coronavirus Disease (COVID-19): A Review of the Literature and Radiologic Perspective.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {332-338}, doi = {10.1053/j.sult.2024.07.003}, pmid = {38996944}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging ; *SARS-CoV-2 ; Tomography, X-Ray Computed/methods ; Emergency Service, Hospital ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the debilitating global pandemic known as Coronavirus disease (COVID-19). In this paper, we highlight the widespread manifestations and complications across disease systems. In addition, we present their relevant imaging findings to inform appropriate investigations and management in patients presenting to the Emergency Department with COVID-19 and its respective sequalae. Of note, we outline considerations for diagnosis of long COVID, an important medium to long term sequalae in patients with previous COVID-19 infections.}, } @article {pmid38995582, year = {2024}, author = {Walbert, H}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {12}, pages = {35}, doi = {10.1007/s15006-024-4072-3}, pmid = {38995582}, issn = {1613-3560}, mesh = {Humans ; *COVID-19 ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Germany ; }, } @article {pmid38994492, year = {2024}, author = {Cahan, J and Finley, JA and Cotton, E and Orban, ZS and Jimenez, M and Weintraub, S and Sorets, T and Koralnik, IJ}, title = {Cognitive functioning in patients with neuro-PASC: the role of fatigue, mood, and hospitalization status.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1401796}, pmid = {38994492}, issn = {1664-2295}, abstract = {This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients' subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with Neuro-PASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study.}, } @article {pmid38992084, year = {2024}, author = {Hadley, E and Yoo, YJ and Patel, S and Zhou, A and Laraway, B and Wong, R and Preiss, A and Chew, R and Davis, H and Brannock, MD and Chute, CG and Pfaff, ER and Loomba, J and Haendel, M and Hill, E and , and Moffitt, R}, title = {Insights from an N3C RECOVER EHR-based cohort study characterizing SARS-CoV-2 reinfections and Long COVID.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {129}, pmid = {38992084}, issn = {2730-664X}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; OTA OT2HL161847//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, abstract = {BACKGROUND: Although the COVID-19 pandemic has persisted for over 3 years, reinfections with SARS-CoV-2 are not well understood. We aim to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection.

METHODS: We use an electronic health record study cohort of over 3 million patients from the National COVID Cohort Collaborative as part of the NIH Researching COVID to Enhance Recovery Initiative. We calculate summary statistics, effect sizes, and Kaplan-Meier curves to better understand COVID-19 reinfections.

RESULTS: Here we validate previous findings of reinfection incidence (6.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present findings that the proportion of Long COVID diagnoses is higher following initial infection than reinfection for infections in the same epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between initial infection and reinfection (chi-squared value: 25,697, p-value: <0.0001) with a medium effect size (Cramer's V: 0.20, DoF = 3). Individuals who experienced severe initial and first reinfection were older in age and at a higher mortality risk than those who had mild initial infection and reinfection.

CONCLUSIONS: In a large patient cohort, we find that the severity of reinfection appears to be associated with the severity of initial infection and that Long COVID diagnoses appear to occur more often following initial infection than reinfection in the same epoch. Future research may build on these findings to better understand COVID-19 reinfections.}, } @article {pmid38992068, year = {2024}, author = {Zang, C and Hou, Y and Schenck, EJ and Xu, Z and Zhang, Y and Xu, J and Bian, J and Morozyuk, D and Khullar, D and Nordvig, AS and Shenkman, EA and Rothman, RL and Block, JP and Lyman, K and Zhang, Y and Varma, J and Weiner, MG and Carton, TW and Wang, F and Kaushal, R}, title = {Identification of risk factors of Long COVID and predictive modeling in the RECOVER EHR cohorts.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {130}, pmid = {38992068}, issn = {2730-664X}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: SARS-CoV-2-infected patients may develop new conditions in the period after the acute infection. These conditions, the post-acute sequelae of SARS-CoV-2 infection (PASC, or Long COVID), involve a diverse set of organ systems. Limited studies have investigated the predictability of Long COVID development and its associated risk factors.

METHODS: In this retrospective cohort study, we used electronic healthcare records from two large-scale PCORnet clinical research networks, INSIGHT (~1.4 million patients from New York) and OneFlorida+ (~0.7 million patients from Florida), to identify factors associated with having Long COVID, and to develop machine learning-based models for predicting Long COVID development. Both SARS-CoV-2-infected and non-infected adults were analysed during the period of March 2020 to November 2021. Factors associated with Long COVID risk were identified by removing background associations and correcting for multiple tests.

RESULTS: We observed complex association patterns between baseline factors and a variety of Long COVID conditions, and we highlight that severe acute SARS-CoV-2 infection, being underweight, and having baseline comorbidities (e.g., cancer and cirrhosis) are likely associated with increased risk of developing Long COVID. Several Long COVID conditions, e.g., dementia, malnutrition, chronic obstructive pulmonary disease, heart failure, PASC diagnosis U099, and acute kidney failure are well predicted (C-index > 0.8). Moderately predictable conditions include atelectasis, pulmonary embolism, diabetes, pulmonary fibrosis, and thromboembolic disease (C-index 0.7-0.8). Less predictable conditions include fatigue, anxiety, sleep disorders, and depression (C-index around 0.6).

CONCLUSIONS: This observational study suggests that association patterns between investigated factors and Long COVID are complex, and the predictability of different Long COVID conditions varies. However, machine learning-based predictive models can help in identifying patients who are at risk of developing a variety of Long COVID conditions.}, } @article {pmid38991485, year = {2024}, author = {Jokela-Pansini, M and Greenhough, B and Cousins, O and Dainow, J}, title = {When you can't find the words: Using body mapping to communicate patients' experiences of Long Covid.}, journal = {Health & place}, volume = {89}, number = {}, pages = {103302}, doi = {10.1016/j.healthplace.2024.103302}, pmid = {38991485}, issn = {1873-2054}, mesh = {Humans ; *COVID-19/psychology ; Communication ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; London ; }, abstract = {The aim of this paper is to reflect on the value of body mapping in supporting patients to communicate their everyday experiences of Long Covid. Body maps are life-sized drawings of bodies and body mapping is used to discuss experiences through guided questions and answering those questions using colours, images and other prompts. This short paper focuses on the first of four body mapping workshops of this study, which was conducted in June 2023 in London with 4 participants in collaboration with Long Covid Support. Our preliminary results suggest i) body mapping can offer novel insights into patients' experiences of Long Covid, ii) the method may be effectively applied as a tool for patients to communicate their symptoms and overall experiences to practitioners, friends, and family members, and iii) body mapping may be adapted to offer peer support as part of Long Covid advocacy. This has significant potential application as a resource for healthcare professionals and patient-led peer support and Long Covid advocacy work.}, } @article {pmid38989751, year = {2024}, author = {Ulusoy, BO and Babaoglu, H and Aypak, BAA and Akinci, E and Kucuksahin, O and Erten, AOS and Erden, A}, title = {Baseline capillaroscopy provides no evidence of microvascular changes to predict long-COVID syndrome.}, journal = {Bratislavske lekarske listy}, volume = {125}, number = {8}, pages = {497-502}, doi = {10.4149/BLL_2024_77}, pmid = {38989751}, issn = {0006-9248}, mesh = {Humans ; *Microscopic Angioscopy/methods ; Male ; *COVID-19/complications ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; SARS-CoV-2 ; Aged ; Microvessels/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Long-COVID refers to a variety of symptoms that continue for at least 4 weeks following the onset of acute COVID-19 infection. "Microclots/microvasculopathy" is a potential cutting-edge theory. Nailfold capillaroscopy is a non-invasive method used to assess microvascularity. In this study, we aimed to compare baseline characteristics and capillaroscopic findings of patients with and without long-COVID syndrome.

METHODS: Baseline clinical characteristics of 53 patients who tested positive for SARS-CoV-2 were recorded. At the time of COVID-19 diagnosis, patients underwent nailfold capillaroscopy. One year later, patients were rescreened for long-COVID symptoms. Comparisons were made between patients with and without long-COVID syndrome in terms of their baseline characteristics and capillaroscopic findings.

RESULTS: There were 35 individuals (66%) with long-COVID syndrome. The most common symptoms related to long-COVID were fatigue (43.4%), myalgia (34%), arthralgia (20.8%), dyspnea (20.8%). In total, 22 patients (41.5%) had abnormal capillaroscopy findings. Like other baseline characteristics, the proportion of patients with abnormal capillaroscopic findings (40% vs 44%, p=0.76) was similar between patients with and without long-COVID syndrome.

CONCLUSION: Microvasculopathy and microthrombotic vascular damage are among the strongest hypotheses discussed in this regard. Our results may suggest that factors, rather than baseline microvasculopathy, may drive pathophysiological mechanism underlying the poorly understood long-COVID syndrome (Tab. 2, Ref. 35).}, } @article {pmid38989384, year = {2024}, author = {Kumar, T and White, AM}, title = {Diagnosis of Graves' Disease and Methimazole-Induced Lupus Erythematosus in an Adolescent Male During the COVID-19 Era: A Case Report.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62023}, pmid = {38989384}, issn = {2168-8184}, abstract = {Graves' disease is the most common form of hyperthyroidism in the pediatric population. Methimazole is the recommended regimen that is well-tolerated in most patients. Treatment with methimazole leading to drug-induced lupus erythematosus (DILE) is not well reported in the pediatric population, especially in the COVID-19 era. We present a case of a 14-year-old Caucasian male who presented with concerns of long COVID due to shortness of breath, hypertension, and fatigue. He was not noted to have significant weight loss, exophthalmos, or sleeping difficulties. He was followed by his general pediatrician, pediatric endocrinologist, cardiologist, and rheumatologist. Laboratory tests confirmed the diagnosis of Graves' disease, and treatment was initiated with methimazole and atenolol. One month into treatment, the patient developed polyarthritis, urticarial rash, and difficulty with gait. Based on clinical suspicion and antibody panels, he was diagnosed with DILE secondary to treatment with methimazole. The patient was then started on a potassium iodide (Lugol) solution to promote the euthyroid state and proceed with total thyroidectomy. Post surgery, the patient developed hypothyroidism, which was managed with oral levothyroxine, to which the patient responded well. By discussing the clinical presentation and treatment of this patient, the goal is to raise awareness and increase clinical suspicion in diagnosing Graves' and DILE in adolescents with upper respiratory presentations.}, } @article {pmid38988667, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1384996}, pmid = {38988667}, issn = {2297-055X}, abstract = {Aging leads to physiological changes, including inflammaging-a chronic low-grade inflammatory state with significant implications for various physiological systems, particularly for cardiovascular health. Concurrently, immunosenescence-the age-related decline in immune function, exacerbates vulnerabilities to cardiovascular pathologies in older individuals. Examining the dynamic connections between immunosenescence, inflammation, and cardiovascular aging, this mini-review aims to disentangle some of these interactions for a better understanding of their complex interplay. In the context of cardiovascular aging, the chronic inflammatory state associated with inflammaging compromises vascular integrity and function, contributing to atherosclerosis, endothelial dysfunction, arterial stiffening, and hypertension. The aging immune system's decline amplifies oxidative stress, fostering an environment conducive to atherosclerotic plaque formation. Noteworthy inflammatory markers, such as the high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, and tumor necrosis factor-alpha emerge as key players in cardiovascular aging, triggering inflammatory signaling pathways and intensifying inflammaging and immunosenescence. In this review we aim to explore the molecular and cellular mechanisms underlying inflammaging and immunosenescence, shedding light on their nuanced contributions to cardiovascular diseases. Furthermore, we explore the reciprocal relationship between immunosenescence and inflammaging, revealing a self-reinforcing cycle that intensifies cardiovascular risks. This understanding opens avenues for potential therapeutic targets to break this cycle and mitigate cardiovascular dysfunction in aging individuals. Furthermore, we address the implications of Long COVID, introducing an additional layer of complexity to the relationship between aging, immunosenescence, inflammaging, and cardiovascular health. Our review aims to stimulate continued exploration and advance our understanding within the realm of aging and cardiovascular health.}, } @article {pmid38987743, year = {2024}, author = {Sha'ari, NI and Ismail, A and Abdul Aziz, AF and Suddin, LS and Azzeri, A and Sk Abd Razak, R and Mad Tahir, NS}, title = {Cardiovascular diseases as risk factors of post-COVID syndrome: a systematic review.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1846}, pmid = {38987743}, issn = {1471-2458}, support = {FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; FRGS/1/2022/SKK04/UKM/02/2//Fundamental Research Grant Scheme (FRGS) under Ministry of Higher Education (MoHE) Malaysia/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Cardiovascular Diseases/epidemiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Survivors/statistics & numerical data ; }, abstract = {BACKGROUND: A growing proportion of people experience incomplete recovery months after contracting coronavirus disease 2019 (COVID-19). These COVID-19 survivors develop a condition known as post-COVID syndrome (PCS), where COVID-19 symptoms persist for > 12 weeks after acute infection. Limited studies have investigated PCS risk factors that notably include pre-existing cardiovascular diseases (CVD), which should be examined considering the most recent PCS data. This review aims to identify CVD as a risk factor for PCS development in COVID-19 survivors.

METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist, systematic literature searches were performed in the PubMed, Scopus, and Web of Science databases from the earliest date available to June 2023. Data from observational studies in English that described the association between CVD and PCS in adults (≥ 18 years old) were included. A minimum of two authors independently performed the screening, study selection, data extraction, data synthesis, and quality assessment (Newcastle-Ottawa Scale). The protocol of this review was registered under PROSPERO (ID: CRD42023440834).

RESULTS: In total, 594 studies were screened after duplicates and non-original articles had been removed. Of the 11 included studies, CVD including hypertension (six studies), heart failure (three studies), and others (two studies) were significantly associated with PCS development with different factors considered. The included studies were of moderate to high methodological quality.

CONCLUSION: Our review highlighted that COVID-19 survivors with pre-existing CVD have a significantly greater risk of developing PCS symptomology than survivors without pre-existing CVD. As heart failure, hypertension and other CVD are associated with a higher risk of developing PCS, comprehensive screening and thorough examinations are essential to minimise the impact of PCS and improve patients' disease progression.}, } @article {pmid38984895, year = {2024}, author = {Judy, J and Yehoshua, A and Gouveia-Pisano, J and Brook, RA and Kleinman, NL and Drnach, AA and Rosenberg, EM and Ghanjanasak, T and Winter, DA and Dai, F and Escobar, JM and Sell, H}, title = {Impact of COVID-19 on work loss in the United States- A retrospective database analysis.}, journal = {Journal of medical economics}, volume = {27}, number = {1}, pages = {941-951}, doi = {10.1080/13696998.2024.2379056}, pmid = {38984895}, issn = {1941-837X}, mesh = {Humans ; *COVID-19/epidemiology/economics ; United States ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; *Sick Leave/statistics & numerical data/economics ; SARS-CoV-2 ; Insurance Claim Review ; Databases, Factual ; Young Adult ; Absenteeism ; }, abstract = {OBJECTIVES: This study investigates the utilization of work absence benefits among United States (US) employees diagnosed with COVID-19, examining frequency, duration, cost, and types of work loss benefits used.

METHODS: This retrospective analysis of the Workpartners Research Reference Database (RRDb) included employees eligible for short- and long-term disability (STD and LTD employer-sponsored benefits, respectively), and other paid work absence benefits from 2018 to 2022. Workpartners RRDb includes over 3.5 million employees from over 500 self-insured employers across the US. Employees were identified by codes from adjudicated medical and disability claims for COVID-19 (2020-2022) and influenza, as well as prescription claims for COVID-19 treatments. Associated payments were quantified for each absence reason.

RESULTS: Approximately 1 million employees were eligible for employer-sponsored paid leave benefits between January 2018 and December 2022. The mean age was 37 years (22% >50 years), and 49.4% were females. COVID-19 was the 2nd most common reason for an STD claim (6.9% of all STD claims) and 13th for an LTD claim (1.7% of all LTD claims) from 2020-2022. The mean duration for COVID-19 STD claims was 24 days (N = 3,731, mean claim=$3,477) versus 10 days for influenza (N = 283, mean claim=$1,721). The mean duration for an LTD claim for COVID-19 was 153 days (N = 11, mean claim=$19,254). Only 21.5% of employees with STD claims in the COVID-19 cohort had prior COVID-19-associated medical or pharmacy claims; over half (range 53%-61%) had documented high risk factors for severe COVID-19.

CONCLUSION: COVID-19 and influenza have the potential to cause work loss in otherwise healthy employees. In this analysis, COVID-19 was the second most frequent reason for an STD claim at the start of the pandemic and remained high (ranked 5th) in 2022. These results highlight the impact of COVID-19 on work loss beyond the acute phase. Comprehensively evaluating work loss implications may help employers prioritize strategies, such as vaccinations and timely treatments, to mitigate the impact of COVID-19 on employees and their companies.}, } @article {pmid38984497, year = {2024}, author = {Avelino-Silva, VI and Bruhn, R and Zurita, KG and Deng, X and Yu, EA and Grebe, E and Stone, M and Lanteri, MC and Spencer, BR and Busch, MP and Custer, B}, title = {SARS-CoV-2 antibody levels and long COVID occurrence in blood donors.}, journal = {Transfusion}, volume = {64}, number = {9}, pages = {1719-1731}, doi = {10.1111/trf.17952}, pmid = {38984497}, issn = {1537-2995}, support = {75D30120C08170/CC/CDC HHS/United States ; 75D30120C08170/CC/CDC HHS/United States ; }, mesh = {Humans ; *Blood Donors/statistics & numerical data ; *COVID-19/immunology/epidemiology/blood ; *SARS-CoV-2/immunology ; Male ; Female ; *Antibodies, Viral/blood ; Middle Aged ; Adult ; Immunoglobulin G/blood ; Post-Acute COVID-19 Syndrome ; Spike Glycoprotein, Coronavirus/immunology ; Aged ; }, abstract = {BACKGROUND: Long COVID is a common condition lacking consensus definition; determinants remain incompletely understood. Characterizing immune profiles associated with long COVID could support the development of preventive and therapeutic strategies.

METHODS: We used a survey to investigate blood donors' infection/vaccination history and acute/persistent symptoms following COVID-19. The prevalence of long COVID was evaluated using self-report and an adapted definition from the RECOVER study. We evaluated factors associated with long COVID, focusing on anti-spike and anti-nucleocapsid SARS-CoV-2 antibodies. Lastly, we investigated long COVID clinical subphenotypes using hierarchical clustering.

RESULTS: Of 33,610 participants, 16,003 (48%) reported having had COVID-19; 1853 (12%) had self-reported long COVID, 685 (4%) met an adapted RECOVER definition, and 2050 (13%) met at least one definition. Higher anti-nucleocapsid levels measured 12-24 weeks post-infection were associated with higher risk of self-reported and RECOVER long COVID. Higher anti-spike IgG levels measured 12-24 weeks post-infection were associated with lower risk of self-reported long COVID. Higher total anti-spike measured 24-48 weeks post-infection was associated with lower risk of RECOVER long COVID. Cluster analysis identified four clinical subphenotypes; patterns included neurological and psychiatric for cluster 1; neurological and respiratory for cluster 2; multi-systemic for cluster 3; and neurological for cluster 4.

DISCUSSION: Long COVID prevalence in blood donors varies depending on the adopted definition. Anti-SARS-CoV-2 antibodies were time-dependently associated with long COVID; higher anti-nucleocapsid levels were associated with higher risk; and higher anti-spike levels were associated with lower risk of long COVID. Different underlying pathophysiologic mechanisms may be associated with distinct clinical subphenotypes.}, } @article {pmid38981586, year = {2024}, author = {Frederick, R and Ierino, F and Lopez, R and Goodman, D}, title = {Impact of cultural diversity on COVID-19 vaccination hesitancy in kidney transplant recipients.}, journal = {Nephrology (Carlton, Vic.)}, volume = {29}, number = {9}, pages = {600-606}, doi = {10.1111/nep.14351}, pmid = {38981586}, issn = {1440-1797}, mesh = {Humans ; Male ; *Kidney Transplantation/adverse effects ; Middle Aged ; Female ; *COVID-19/prevention & control/epidemiology ; Retrospective Studies ; *Vaccination Hesitancy/statistics & numerical data/psychology ; *COVID-19 Vaccines/administration & dosage ; Cultural Diversity ; Aged ; SARS-CoV-2 ; Vaccination/statistics & numerical data ; Transplant Recipients/statistics & numerical data/psychology ; Australia/epidemiology ; Adult ; }, abstract = {AIM: To study COVID-19 vaccination status in kidney transplant recipients (KTRs), reasons for incomplete vaccination and the clinical impact of vaccination on patient outcomes.

METHODS: A single-centre retrospective analysis of KTR (n = 543) conducted between 1970 and December 2022. Data included baseline demographics, number of vaccinations, reason for incomplete vaccination and patient outcomes following COVID-19 infection. A completed course of COVID-19 vaccination was defined as four or more vaccine doses.

EXCLUSION CRITERIA: those deceased prior December 2019, managed by another health service, failed graft, or deceased secondary to non-COVID cause.

RESULTS: 273 of 543 patients met inclusion criteria. Mean age was 58.1 ± 12.2 years, 66% were male. 58.2% of patients were fully vaccinated, 22.7% received three doses, 7.7% received two doses, 0.7% received one dose, 0.7% received zero doses, and 10% incomplete records. The most common reasons for incomplete vaccination were COVID-19 infection, concern for side effects, and patient unawareness of booster recommendations. Vaccination uptake was greater in Australian born patients compared with those born overseas, odds ratio 0.40 (95% CI 0.23-0.69). KTR with incomplete vaccination had poorer outcomes, higher rate of AKI, long COVID, and increased hospitalization.

CONCLUSION: The majority of KTR were fully vaccinated. KTR with incomplete vaccination status had poorer outcomes with COVID-19 infection and other issues. Patient education is a major area for improvement targeting patients born overseas and better information regarding side effects. Potential interventions need to address improved communication, cultural relevancy, and language.}, } @article {pmid38979547, year = {2024}, author = {Budikayanti, A and Hakim, M and Mutiani, F and Handayani, S and Lailiyya, N and Khosama, H and Jehosua, SY and Puspitasari, V and Gunawan, PY and Hambarsari, Y and Islamiyah, WR and Gofir, A and Vidyanti, AN and Devicaesaria, A and Ibonita, R and Suryawati, H and Tedjasukmana, R}, title = {The Impact of Post-COVID-19 Conditions on Sleep and Quality of Life in Indonesia: A Nationwide Cross-Sectional Study.}, journal = {Nature and science of sleep}, volume = {16}, number = {}, pages = {907-916}, pmid = {38979547}, issn = {1179-1608}, abstract = {BACKGROUND: Sleep disturbances are included in the six most commonly cited complaints in post-COVID-19 conditions. In order to find the optimal management approach and enhance Quality of Life (QoL), we intend to explore sleep disturbances that occur in post-COVID-19 conditions.

METHODS: This was a cross-sectional study conducted with interviews and questionnaires using the Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, Insomnia Severity Index (ISI) for assessing insomnia, Epworth Sleepiness Scale (ESS) for assessing Excessive Daytime Sleepiness (EDS), STOP-BANG questionnaire for assessing Obstructive Sleep Apnea (OSA), and Short Form 36 (SF-36) for assessing QoL. We recruited respondents from several cities in Indonesia and performed an analysis to find the relationship between sleep disturbance and its association with QoL.

RESULTS: This study involved 757 respondents. They were predominantly female, with a median age of 39 years, no comorbidities, and had exhibited mild COVID-19 severity. Subjects with post-COVID-19 conditions experienced insomnia, poor sleep quality, normal sleepiness, and low risk of OSA. Sleep quality caused role limitations due to decreased physical and mental health. Insomnia caused role limitations due to emotional and social functioning problems. Meanwhile, OSA only affected physical functioning.

CONCLUSION: Numerous aspects of patients' QoL are affected by sleep disturbance in post-COVID-19 conditions. A comprehensive approach and coordinated care pathways must be effectively managed to improve QoL among individuals experiencing sleep disturbance.}, } @article {pmid38979186, year = {2024}, author = {Xiong, R and Fleming, E and Caldwell, R and Vernon, SD and Kozhaya, L and Gunter, C and Bateman, L and Unutmaz, D and Oh, J}, title = {BioMapAI: Artificial Intelligence Multi-Omics Modeling of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979186}, issn = {2692-8205}, support = {R01 AR078634/AR/NIAMS NIH HHS/United States ; U19 AI142733/AI/NIAID NIH HHS/United States ; U54 NS105539/NS/NINDS NIH HHS/United States ; R21 AR075174/AR/NIAMS NIH HHS/United States ; DP2 GM126893/GM/NIGMS NIH HHS/United States ; }, abstract = {Chronic diseases like ME/CFS and long COVID exhibit high heterogeneity with multifactorial etiology and progression, complicating diagnosis and treatment. To address this, we developed BioMapAI, an explainable Deep Learning framework using the richest longitudinal multi-'omics dataset for ME/CFS to date. This dataset includes gut metagenomics, plasma metabolome, immune profiling, blood labs, and clinical symptoms. By connecting multi-'omics to asymptom matrix, BioMapAI identified both disease- and symptom-specific biomarkers, reconstructed symptoms, and achieved state-of-the-art precision in disease classification. We also created the first connectivity map of these 'omics in both healthy and disease states and revealed how microbiome-immune-metabolome crosstalk shifted from healthy to ME/CFS. Thus, we proposed several innovative mechanistic hypotheses for ME/CFS: Disrupted microbial functions - SCFA (butyrate), BCAA (amino acid), tryptophan, benzoate - lost connection with plasma lipids and bile acids, and activated inflammatory and mucosal immune cells (MAIT, γδT cells) with INFγ and GzA secretion. These abnormal dynamics are linked to key disease symptoms, including gastrointestinal issues, fatigue, and sleep problems.}, } @article {pmid38978683, year = {2024}, author = {Li, L and Zhou, T and Lu, Y and Chen, J and Lei, Y and Wu, Q and Arnold, J and Becich, MJ and Bisyuk, Y and Blecker, S and Chrischilles, E and Christakis, DA and Geary, CR and Jhaveri, R and Lenert, L and Liu, M and Mirhaji, P and Morizono, H and Mosa, ASM and Onder, AM and Patel, R and Smoyer, WE and Taylor, BW and Williams, DA and Dixon, BP and Flynn, JT and Gluck, C and Harshman, LA and Mitsnefes, MM and Modi, ZJ and Pan, CG and Patel, HP and Verghese, PS and Forrest, CB and Denburg, MR and Chen, Y}, title = {Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38978683}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; UM1 TR004400/TR/NCATS NIH HHS/United States ; }, abstract = {We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m[2], End Stage Kidney Disease diagnosis, dialysis, or transplant.}, } @article {pmid38978664, year = {2024}, author = {Jiang, S and Loomba, J and Zhou, A and Sharma, S and Sengupta, S and Liu, J and Brown, D}, title = {A Bayesian Survival Analysis on Long COVID and non Long COVID patients: A Cohort Study Using National COVID Cohort Collaborative (N3C) Data.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38978664}, support = {75N99023D00001/OF/ORFDO NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; 75N95021D00001/DA/NIDA NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; 75N92023D00001/HL/NHLBI NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; 75N90023D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Since the outbreak of COVID-19 pandemic in 2020, numerous researches and studies have focused on the long-term effects of COVID infection. The Centers for Disease Control (CDC) implemented an additional code into the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for reporting 'Post COVID-19 condition, unspecified (U09.9)' effective on October 1st 2021, representing that Long COVID is a real illness with potential chronic conditions. The National COVID Cohort Collaborative (N3C) provides researchers with abundant electronic health records (EHR) data by aggregating and harmonizing EHR data across different clinical organizations in the United States, making it convenient to build up a survival analysis on Long COVID patients and non Long COVID patients among large amounts of COVID positive patients.}, } @article {pmid38978145, year = {2024}, author = {Tang, L and Wang, Y and Li, X and Yang, L and Luo, Y and Li, C and He, Y}, title = {Epidemiological characteristics of first-time SARS-CoV-2 Omicron infection among hospital staff in Chengdu, China.}, journal = {Journal of health, population, and nutrition}, volume = {43}, number = {1}, pages = {104}, pmid = {38978145}, issn = {2072-1315}, mesh = {Humans ; *COVID-19/epidemiology ; China/epidemiology ; Female ; Male ; Adult ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Personnel, Hospital/statistics & numerical data ; Surveys and Questionnaires ; Incidence ; Disease Outbreaks ; Risk Factors ; COVID-19 Vaccines/administration & dosage ; Young Adult ; }, abstract = {BACKGROUND: After China ended its 'dynamic zero-COVID policy' on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected.

METHODS: All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection.

RESULTS: A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07-1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57-16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19-0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23-0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22-0.97 for within 1-3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms.

CONCLUSION: Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China's deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.}, } @article {pmid38977844, year = {2024}, author = {Pietzner, M and Denaxas, S and Yasmeen, S and Ulmer, MA and Nakanishi, T and Arnold, M and Kastenmüller, G and Hemingway, H and Langenberg, C}, title = {Complex patterns of multimorbidity associated with severe COVID-19 and long COVID.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {94}, pmid = {38977844}, issn = {2730-664X}, support = {U19 AG074879/AG/NIA NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; R01 AG081322/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses are scarce but may help to understand severe COVID-19 among patients at supposedly low risk.

METHODS: We systematically harmonized >12 million primary care and hospitalisation health records from ~500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID.

RESULTS: Here we identify 679 diseases associated with an increased risk for severe COVID-19 (n = 672) and/or Long COVID (n = 72) that span almost all clinical specialties and are strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we establish consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This includes a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observe partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis or rheumatoid arthritis, possibly indicating a segregation of disease mechanisms.

CONCLUSIONS: Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple - including non-fatal - conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.}, } @article {pmid38977629, year = {2024}, author = {Pszczołowska, M and Walczak, K and Miśków, W and Antosz, K and Batko, J and Karska, J and Leszek, J}, title = {Correction to: Molecular cross‑talk between long COVID‑19 and Alzheimer's disease.}, journal = {GeroScience}, volume = {46}, number = {5}, pages = {5393}, doi = {10.1007/s11357-024-01271-4}, pmid = {38977629}, issn = {2509-2723}, } @article {pmid38975933, year = {2024}, author = {Jastifer, JR and Jastifer, EJ and Hoffman, MD}, title = {COVID-19 Infection in Ultramarathon Runners: Findings of the Ultrarunners Longitudinal TRAcking Study.}, journal = {Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine}, volume = {34}, number = {6}, pages = {597-602}, doi = {10.1097/JSM.0000000000001252}, pmid = {38975933}, issn = {1536-3724}, mesh = {Humans ; *COVID-19/epidemiology ; Longitudinal Studies ; Male ; Middle Aged ; *Marathon Running ; Adult ; Female ; SARS-CoV-2 ; Fatigue/etiology ; Aged ; Running ; Hospitalization/statistics & numerical data ; }, abstract = {OBJECTIVE: Ultramarathon runners are a unique patient population who have been shown to have a lower rate of severe chronic medical conditions. This study aimed to determine the effect that COVID-19 infection has had on this population and their running behavior.

DESIGN: The Ultrarunners Longitudinal TRAcking (ULTRA) Study is a large longitudinal study of ultramarathon runners. Questions on health status, running behavior, and COVID-19 infection were included in the most recent survey.

SETTING: Community survey.

PARTICIPANTS: Seven hundred thirty-four ultramarathon runners participated in the study.

INTERVENTIONS: None.

MAIN OUTCOME MEASURES: Personal, exercise, and COVID-19 infection history.

RESULTS: 52.7% of study participants reported having been symptomatic from a COVID-19 infection, with 6.7% testing positive multiple times. Participants required a total of 4 days of hospitalization. The most common symptoms included fever (73.6%), fatigue (68.5%), sore throat (68.2%), runny nose (67.7%), and cough (67.4%). Cardiovascular symptoms, which are of particular interest in the running population, included shortness of breath (46.3%), tachycardia (44.7%), chest pain (36.2%), and wheezing (33.3%). A total of 50 subjects (6.8%) reported long COVID (symptoms lasting more than 12 weeks).

CONCLUSIONS: Severe COVID-19 infection has been rare in this population of ultramarathon runners, although symptomatic infection that affects running is common. To support the well-being of this group of highly active athletes, clinicians should appreciate that cardiovascular symptoms are common and the long-term significance of these symptoms in runners is unknown.

LEVEL OF EVIDENCE: Level 2 prospective study.}, } @article {pmid38975007, year = {2024}, author = {Seostianin, M and Burchardt, P}, title = {Myocardial involvement in post-COVID-19 condition: a note from the surgical approach.}, journal = {Cardiovascular diagnosis and therapy}, volume = {14}, number = {3}, pages = {314-317}, pmid = {38975007}, issn = {2223-3652}, } @article {pmid38973985, year = {2024}, author = {Dalmau, R and Alanazi, AM and Arora, M and Banerjee, A and Bianco, E and Gaalema, DE and Goma, FM and Hasegawa, K and Komiyama, M and Pérez Ríos, M and Willett, J and Wang, Y}, title = {A Complex Interplay: Navigating the Crossroads of Tobacco Use, Cardiovascular Disease, and the COVID-19 Pandemic: A WHF Policy Brief.}, journal = {Global heart}, volume = {19}, number = {1}, pages = {55}, pmid = {38973985}, issn = {2211-8179}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Cardiovascular Diseases/epidemiology/prevention & control ; *Tobacco Use/epidemiology ; *SARS-CoV-2 ; Pandemics ; Risk Factors ; Health Policy ; }, abstract = {The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans.}, } @article {pmid38972603, year = {2024}, author = {Yotsuyanagi, H and Ohmagari, N and Doi, Y and Yamato, M and Fukushi, A and Imamura, T and Sakaguchi, H and Sonoyama, T and Sanaki, T and Ichihashi, G and Tsuge, Y and Uehara, T and Mukae, H}, title = {Prevention of post COVID-19 condition by early treatment with ensitrelvir in the phase 3 SCORPIO-SR trial.}, journal = {Antiviral research}, volume = {229}, number = {}, pages = {105958}, doi = {10.1016/j.antiviral.2024.105958}, pmid = {38972603}, issn = {1872-9096}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Antiviral Agents/therapeutic use ; *COVID-19 Drug Treatment ; Double-Blind Method ; Indazoles ; *Post-Acute COVID-19 Syndrome/prevention & control ; *SARS-CoV-2/drug effects ; Treatment Outcome ; Triazines ; Triazoles ; }, abstract = {This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 h of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.6-36.5 years; men, 53.3%-58.3%). On days 85, 169, and 337, ensitrelvir 125-mg treatment showed 32.7% (95% confidence interval [CI]: -30.6, 66.1), 21.5% (95% CI: -37.3, 55.6), and 24.6% (95% CI: -43.7, 60.9) reductions versus placebo, respectively, in the risk of any of the 14 acute-phase COVID-19 symptoms (at least one mild, moderate, or severe symptom with general health not returning to the usual level). Ensitrelvir 250-mg treatment showed 10.9% (95% CI: -67.0, 52.8), 9.5% (95% CI: -56.6, 48.0), and 30.6% (95% CI: -36.2, 65.5) risk reductions versus placebo on days 85, 169, and 337, respectively. Risk reductions were observed in any of the 4 neurological symptoms and were more pronounced among patients with high acute-phase symptom scores at baseline and among those with a baseline body mass index ≥25 kg/m[2]. Ensitrelvir treatment in the acute phase of COVID-19 may reduce the risk of various symptoms associated with PCC. TRIAL REGISTRATION NUMBER: jRCT2031210350.}, } @article {pmid38971080, year = {2024}, author = {Gao, Y and Shen, Q and Zang, Y and Miao, T and Yang, M and Liu, Y and Zheng, X and Shen, S and Wu, W}, title = {COVID-19 vaccination and long COVID among 50 years older and above European: The role of chronic multimorbidity.}, journal = {Archives of gerontology and geriatrics}, volume = {126}, number = {}, pages = {105554}, doi = {10.1016/j.archger.2024.105554}, pmid = {38971080}, issn = {1872-6976}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Male ; Female ; *Multimorbidity ; Aged ; Europe/epidemiology ; Middle Aged ; Cross-Sectional Studies ; *COVID-19 Vaccines/administration & dosage ; Vaccination/statistics & numerical data ; SARS-CoV-2 ; Chronic Disease/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; }, abstract = {BACKGROUND AND AIMS: We aimed to explore the association between coronavirus disease-19 (COVID-19) vaccination and long COVID according to the status of chronic multimobidity.

METHODS: A total of 1913 participants were recruited in the cross-sectional study on the basis of the Survey of Health and Retirement in Europe. COVID-19 vaccination was defined as vaccination within the last 12 months. Chronic multimorbidity was defined as history of 2 + chronic disease. The study outcome was long COVID during the 12-month follow-up. Multivariable logistic models were performed to estimate the influence of chronic multimorbidity on the association of vaccination with long COVID. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated.

RESULTS: Chronic multimorbidity significantly modified the association of COVID-19 vaccination with long COVID (Pinteraction = 0.024). The rates of study outcome were significantly lower among vaccinated participants in the chronic multimorbidity subgroup, but not in the other subgroup. Multivariable odds ratios (95 % confidence intervals) of study outcome for unvaccination vs. vaccination were 1.494 (1.013-2.203) in those with multimorbidity and 0.915 (0.654-1.280) in those without multimorbidity, respectively. Adding COVID-19 vaccination to a model containing conventional risk factors significantly improved risk reclassification for study outcome among those with chronic multimobidity (continuous NRI was 25.39 % [P = 0.002] and IDI was 0.42 % [P = 0.075]) CONCLUSION: An inverse association of COVID-19 vaccination with long COVID was found among participants with chronic multimorbidity, but not among those without chronic multimorbidity. Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years.}, } @article {pmid38970653, year = {2024}, author = {Rudroff, T}, title = {Frontal-striatal glucose metabolism and fatigue in patients with multiple sclerosis, long COVID, and COVID-19 recovered controls.}, journal = {Experimental brain research}, volume = {242}, number = {9}, pages = {2125-2136}, pmid = {38970653}, issn = {1432-1106}, support = {Roy J. and Lucille A. Carver College of Medicine, University of Iowa//Roy J. and Lucille A. Carver College of Medicine, University of Iowa/ ; Instrumentation Grant 1S10OD025025-01.//Instrumentation Grant 1S10OD025025-01./ ; RAMCHARGE (Colorado State University)//RAMCHARGE (Colorado State University)/ ; Colorado Translational Research Imaging Center (C-TRIC) at University of Colorado School of Medicine, Denver, CO.//Colorado Translational Research Imaging Center (C-TRIC) at University of Colorado School of Medicine, Denver, CO./ ; }, mesh = {Humans ; *COVID-19/complications/metabolism ; Female ; Male ; Middle Aged ; *Multiple Sclerosis/metabolism/complications/diagnostic imaging/physiopathology ; *Fatigue/metabolism/physiopathology/diagnostic imaging/etiology ; *Positron-Emission Tomography ; Adult ; *Glucose/metabolism ; *Corpus Striatum/metabolism/diagnostic imaging ; Fluorodeoxyglucose F18 ; Frontal Lobe/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7-1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses.}, } @article {pmid38970055, year = {2024}, author = {Löhn, M and Wirth, KJ}, title = {Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {630}, pmid = {38970055}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/drug therapy ; *TRPM Cation Channels/metabolism ; *Naltrexone/therapeutic use/pharmacology/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Treatment Outcome ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurological, cardiovascular, microvascular, and skeletal muscular findings, no biomarkers have been identified. The Transient receptor potential melastatin 3 (TRPM3) channel, involved in pain transduction, thermosensation, transmitter and neuropeptide release, mechanoregulation, vasorelaxation, and immune defense, shows altered function in ME/CFS. Dysfunction of TRPM3 in natural killer (NK) cells, characterized by reduced calcium flux, has been observed in ME/CFS and PCS patients, suggesting a role in ineffective pathogen clearance and potential virus persistence and autoimmunity development. TRPM3 dysfunction in NK cells can be improved by naltrexone in vitro and ex vivo, which may explain the moderate clinical efficacy of low-dose naltrexone (LDN) treatment. We propose that TRPM3 dysfunction may have a broader involvement in ME/CFS pathophysiology, affecting other organs. This paper discusses TRPM3's expression in various organs and its potential impact on ME/CFS symptoms, with a focus on small nerve fibers and the brain, where TRPM3 is involved in presynaptic GABA release.}, } @article {pmid38969238, year = {2024}, author = {Halme, ALE and Laakkonen, S and Rutanen, J and Nevalainen, OPO and Sinisalo, M and Horstia, S and Mustonen, JMJ and Pourjamal, N and Vanhanen, A and , and Rosberg, T and Renner, A and Perola, M and Paukkeri, EL and Patovirta, RL and Parkkila, S and Paajanen, J and Nykänen, T and Mäntylä, J and Myllärniemi, M and Mattila, T and Leinonen, MK and Külmäsu, A and Kuutti, P and Kuitunen, I and Kreivi, HR and Kilpeläinen, TP and Kauma, H and Kalliala, IEJ and Järvinen, P and Hankkio, R and Hammarén, T and Feuth, T and Ansakorpi, H and Ala-Karvia, R and Guyatt, GH and Tikkinen, KAO}, title = {Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial.}, journal = {The Journal of infection}, volume = {89}, number = {3}, pages = {106217}, doi = {10.1016/j.jinf.2024.106217}, pmid = {38969238}, issn = {1532-2742}, mesh = {Humans ; *Imatinib Mesylate/therapeutic use ; Female ; Male ; Middle Aged ; *Quality of Life ; *COVID-19/mortality ; *Hospitalization/statistics & numerical data ; Aged ; *SARS-CoV-2 ; *COVID-19 Drug Treatment ; Treatment Outcome ; Adult ; }, abstract = {OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients.

METHODS: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients.

RESULTS: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence).

CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.}, } @article {pmid38967606, year = {2024}, author = {Marcinkiewicz, J}, title = {Increase in the incidence of invasive bacterial infections following the COVID-19 pandemic: potential links with decreased herd trained immunity - a novel concept in medicine.}, journal = {Polish archives of internal medicine}, volume = {134}, number = {9}, pages = {}, doi = {10.20452/pamw.16794}, pmid = {38967606}, issn = {1897-9483}, mesh = {Humans ; *COVID-19/immunology/epidemiology ; Incidence ; Immunity, Herd ; Immunity, Innate ; Bacterial Infections/immunology/epidemiology ; SARS-CoV-2/immunology ; Pandemics ; Streptococcal Infections/immunology/epidemiology ; Streptococcus pyogenes/immunology ; Trained Immunity ; }, abstract = {A global increase in the incidence of various infectious diseases has been observed since the end of the COVID‑19 pandemic. This may be due to 2 independent phenomena. One of them is impaired immunity of long‑COVID patients. The second (major) one is associated with long‑term isolation of many people during the global pandemic‑related lockdown, resulting in an extreme reduction of exposure to natural environmental human microbiota. This, in turn, led to a silencing state of the body's defense systems, including a decline of the prepandemic trained immunity (innate memory), which only persists for weeks to months after exposure to a pathogen. This decrease in the performance of trained immunity may be especially important for morbidity of infectious diseases without currently available vaccines, such as invasive group A Streptococcus pyogenes (GAS) infections, primarily streptococcal toxic shock syndrome. This review discusses data that support an important role of trained macrophages in host defense, and demonstrates the potential clinical implications of β‑glucan, the major inducer of trained macrophages, for prophylactic and therapeutic use in individuals with impaired personal innate immunity. Altogether, it might be speculated that trained innate immunity within an entire population can lead to the development of herd trained immunity (HTI), a newly‑coined medical term. HTI can supplement classic, antigen‑specific herd immunity (memory B and T cells), and it plays a key role in preventing the spread of various infectious diseases, including invasive GAS infections. Unfortunately, the global HTI has been overthrown during the COVID‑19 pandemic; however, it should be restored shortly.}, } @article {pmid38967104, year = {2024}, author = {Thurgur, H and Lynskey, M and Schlag, AK and Croser, C and Nutt, DJ and Iveson, E}, title = {Authors' response to letter 'On the use of open-label studies for the evaluation of cannabis-based products for the treatment of long-COVID'.}, journal = {British journal of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bcp.16174}, pmid = {38967104}, issn = {1365-2125}, } @article {pmid38966550, year = {2024}, author = {Joung, JY and Lee, JS and Choi, Y and Kim, YJ and Oh, HM and Seo, HS and Son, CG}, title = {Evaluating myelophil, a 30% ethanol extract of Astragalus membranaceus and Salvia miltiorrhiza, for alleviating fatigue in long COVID: a real-world observational study.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1394810}, pmid = {38966550}, issn = {1663-9812}, abstract = {BACKGROUND: Persistent post-infectious symptoms, predominantly fatigue, characterize Long COVID. This study investigated the efficacy of Myelophil (MYP), which contains metabolites extracted from Astragalus membranaceus and Salvia miltiorrhiza using 30% ethanol, in alleviating fatigue among subjects with Long COVID.

METHODS: In this prospective observational study, we enrolled subjects with significant fatigue related to Long COVID, using criteria of scores of 60 or higher on the modified Korean Chalder Fatigue scale (mKCFQ11), or five or higher on the Visual Analog Scale (VAS) for brain fog. Utilizing a single-arm design, participants were orally administered MYP (2,000 mg daily) for 4 weeks. Changes in fatigue severity were assessed using mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain fog. In addition, changes in quality of life using the short form 12 (SF-12) were also assessed along with plasma cortisol levels.

RESULTS: A total of 50 participants (18 males, 32 females) were enrolled; 49 were included in the intention-to-treat analysis with scores of 66.9 ± 11.7 on mKCFQ11 and 6.3 ± 1.5 on the brain fog VAS. After 4 weeks of MYP administration, there were statistically significant improvements in fatigue levels: mKCFQ11 was measured at 34.8 ± 17.1 and brain fog VAS at 3.0 ± 1.9. Additionally, MFI-20 decreased from 64.8 ± 9.8 to 49.3 ± 10.8, fatigue VAS dropped from 7.4 ± 1.0 to 3.4 ± 1.7, SF-12 scores rose from 53.3 ± 14.9 to 78.6 ± 14.3, and plasma cortisol levels also elevated from 138.8 ± 50.1 to 176.9 ± 62.0 /mL. No safety concerns emerged during the trial.

CONCLUSION: Current findings underline MYP's potential in managing Long COVID-induced fatigue. However, comprehensive studies remain imperative.

CLINICAL TRIAL REGISTRATION: https://cris.nih.go.kr, identifier KCT0008948.}, } @article {pmid38966504, year = {2024}, author = {Sarfraz, A and Sarfraz, Z and Bano, S and Sarfraz, M and Jaan, A and Minhas, A and Razzack, AA and Patel, G and Manish, KC and Makkar, SS and Garimella, R and Pandav, K and Almonte, J and Paul, T and Almonte, T and Jimenez, L and Pantoga, JC and El Mazboudi, N and Yatzkan, G and Michel, G and Michel, J}, title = {Global Perspective on COVID-19 Therapies, Cardiovascular Outcomes, and Implications for Long COVID: A State-of-the-Art Review.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {14}, number = {2}, pages = {58-66}, pmid = {38966504}, issn = {2000-9666}, abstract = {The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.}, } @article {pmid38966282, year = {2024}, author = {Perez, O and Santibañez, M and Rasines, L and Castillo, JM and Aginagalde-Llorente, AH}, title = {Long-Term Patient Symptoms and Quality of Life in Adults After COVID-19: A Real Life Study.}, journal = {Open respiratory archives}, volume = {6}, number = {3}, pages = {100336}, pmid = {38966282}, issn = {2659-6636}, abstract = {OBJECTIVE: To characterize long-term patient-reported symptoms and quality of life, in adults after COVID-19.

MATERIAL AND METHODS: Cross-sectional study in Cantabria (Northern Spain) including adults with PCR-confirmed SARS-CoV-2 infection (n = 694) with a time period between 4.7 and 24 month post-SARS-CoV-2 diagnosis, and their close contacts (n = 663) (PCR negative and without suspected infection) obtained from simple random sampling of a total of 47,773 cases and 94,301 close contacts. The ISARIC survey was used as screening tool with self-reported "non-feeling fully recovery (NFFR)" defined as primary outcome.

RESULTS: 16.57% (n = 115/694) reported NFFR. Most prevalent symptoms were in order of frequency: Fatigue (54.8%); Loss of smell (40.9%); Problems speaking or communicating (29.6%); Loss of taste (28.7%); Confusion/lack of concentration (27.8%); Persistent muscle pain (24.3%) and Shortness of breath/breathlessness (23.5%). When comparing the three ordinal groups (Close contacts, COVID-19 feeling recovered, and COVID-19 NFFR) the prevalence of these symptoms was increasingly higher among each ordinal group (p < 0.001). Female gender was significantly associated with NFFR: (adjusted odds ratio (aOR) = 1.56); as well as older age: aOR per 10 year increment = 1.15. Lastly, they scored on average 9.63 points less in Euroquol.

CONCLUSIONS: More than 15% of patients in our real-life population-based study, reported NFFR, being female sex and older age independent predictors of this condition. Most symptoms in these patients were in accordance with WHO definition of post COVID-19 condition in adults, and were less prevalent in COVID-19 feeling recovered and close contact respectively, with a statistically significant dose-response pattern, and with a large decrease in quality of life according to Euroquol.}, } @article {pmid38965890, year = {2024}, author = {Volcic, M and Nchioua, R and Pastorio, C and Zech, F and Haußmann, I and Sauter, D and Read, C and Walther, P and Kirchhoff, F}, title = {Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model.}, journal = {Journal of medical virology}, volume = {96}, number = {7}, pages = {e29783}, doi = {10.1002/jmv.29783}, pmid = {38965890}, issn = {1096-9071}, support = {//SA 2676/3-1/ ; //Deutsche Forschungsgemeinschaft (DFG) under CRC1279/ ; }, mesh = {Humans ; *SARS-CoV-2/pathogenicity ; Caco-2 Cells ; *Virus Replication ; *COVID-19/virology/pathology ; *Intestinal Mucosa/virology/pathology ; *Tight Junctions/virology ; Alanine/analogs & derivatives ; Zonula Occludens-1 Protein/metabolism/genetics ; Antiviral Agents/pharmacology ; HT29 Cells ; Occludin/metabolism/genetics ; Adenosine Monophosphate/analogs & derivatives ; }, abstract = {Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function is thought to play a key role in Long COVID. Despite its importance, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin, and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir, the fusion inhibitor EK1 and the transmembrane serine protease 2 inhibitor Camostat inhibited SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.}, } @article {pmid38965510, year = {2024}, author = {Sk Abd Razak, R and Ismail, A and Abdul Aziz, AF and Suddin, LS and Azzeri, A and Sha'ari, NI}, title = {Post-COVID syndrome prevalence: a systematic review and meta-analysis.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1785}, pmid = {38965510}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Since the Coronavirus disease 2019 (COVID-19) pandemic began, the number of individuals recovering from COVID-19 infection have increased. Post-COVID Syndrome, or PCS, which is defined as signs and symptoms that develop during or after infection in line with COVID-19, continue beyond 12 weeks, and are not explained by an alternative diagnosis, has also gained attention. We systematically reviewed and determined the pooled prevalence estimate of PCS worldwide based on published literature.

METHODS: Relevant articles from the Web of Science, Scopus, PubMed, Cochrane Library, and Ovid MEDLINE databases were screened using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic search process. The included studies were in English, published from January 2020 to April 2024, had overall PCS prevalence as one of the outcomes studied, involved a human population with confirmed COVID-19 diagnosis and undergone assessment at 12 weeks post-COVID infection or beyond. As the primary outcome measured, the pooled prevalence of PCS was estimated from a meta-analysis of the PCS prevalence data extracted from individual studies, which was conducted via the random-effects model. This study has been registered on PROSPERO (CRD42023435280).

RESULTS: Forty eight studies met the eligibility criteria and were included in this review. 16 were accepted for meta-analysis to estimate the pooled prevalence for PCS worldwide, which was 41.79% (95% confidence interval [CI] 39.70-43.88%, I[2] = 51%, p = 0.03). Based on different assessment or follow-up timepoints after acute COVID-19 infection, PCS prevalence estimated at ≥ 3rd, ≥ 6th, and ≥ 12th months timepoints were each 45.06% (95% CI: 41.25-48.87%), 41.30% (95% CI: 34.37-48.24%), and 41.32% (95% CI: 39.27-43.37%), respectively. Sex-stratified PCS prevalence was estimated at 47.23% (95% CI: 44.03-50.42%) in male and 52.77% (95% CI: 49.58-55.97%) in female. Based on continental regions, pooled PCS prevalence was estimated at 46.28% (95% CI: 39.53%-53.03%) in Europe, 46.29% (95% CI: 35.82%-56.77%) in America, 49.79% (95% CI: 30.05%-69.54%) in Asia, and 42.41% (95% CI: 0.00%-90.06%) in Australia.

CONCLUSION: The prevalence estimates in this meta-analysis could be used in further comprehensive studies on PCS, which might enable the development of better PCS management plans to reduce the effect of PCS on population health and the related economic burden.}, } @article {pmid38965271, year = {2024}, author = {Danzer, B and Jukic, M and Dunkel, A and Andersen, G and Lieder, B and Schaudy, E and Stadlmayr, S and Lietard, J and Michel, T and Krautwurst, D and Haller, B and Knolle, P and Somoza, M and Lingor, P and Somoza, V}, title = {Impaired metal perception and regulation of associated human foliate papillae tongue transcriptome in long-COVID-19.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {15408}, pmid = {38965271}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/virology/genetics/metabolism ; Male ; Female ; *Transcriptome ; Adult ; *SARS-CoV-2 ; Middle Aged ; *Tongue/metabolism/virology/pathology ; Immunoglobulin G ; Metals/metabolism ; Taste Buds/metabolism ; Taste Perception/genetics ; Taste ; Receptors, Odorant/genetics/metabolism ; Olfactory Perception ; }, abstract = {Chemosensory impairment is an outstanding symptom of SARS-CoV-2 infections. We hypothesized that measured sensory impairments are accompanied by transcriptomic changes in the foliate papillae area of the tongue. Hospital personnel with known SARS-CoV-2 immunoglobulin G (IgG) status completed questionnaires on sensory perception (n = 158). A subcohort of n = 141 participated in forced choice taste tests, and n = 43 participants consented to donate tongue swabs of the foliate papillae area for whole transcriptome analysis. The study included four groups of participants differing in IgG levels (≥ 10 AU/mL = IgG[+]; < 10 AU/mL = IgG[-]) and self-reported sensory impairment (SSI[±]). IgG[+] subjects not detecting metallic taste had higher IgG[+] levels than IgG[+] participants detecting iron gluconate (p = 0.03). Smell perception was the most impaired biological process in the transcriptome data from IgG[+]/SSI[+] participants subjected to gene ontology enrichment. IgG[+]/SSI[+] subjects demonstrated lower expression levels of 166 olfactory receptors (OR) and 9 taste associated receptors (TAS) of which OR1A2, OR2J2, OR1A1, OR5K1 and OR1G1, as well as TAS2R7 are linked to metallic perception. The question raised by this study is whether odorant receptors on the tongue (i) might play a role in metal sensation, and (ii) are potential targets for virus-initiated sensory impairments, which needs to be investigated in future functional studies.}, } @article {pmid38964752, year = {2024}, author = {Gorbenko, AA and Cohen, AA}, title = {On the use of open-label studies for the evaluation of cannabis-based products for the treatment of long COVID.}, journal = {British journal of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bcp.16169}, pmid = {38964752}, issn = {1365-2125}, } @article {pmid38963942, year = {2024}, author = {Francavilla, B and Velletrani, G and Fiorelli, D and Maurantonio, S and Passali, FM and Schirinzi, T and Bernardini, S and Di Girolamo, S and Nuccetelli, M}, title = {Circulating calprotectin as a potential biomarker of persistent olfactory dysfunctions in Post-COVID-19 patients.}, journal = {Cytokine}, volume = {181}, number = {}, pages = {156688}, doi = {10.1016/j.cyto.2024.156688}, pmid = {38963942}, issn = {1096-0023}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anosmia/blood ; *Biomarkers/blood ; *COVID-19/blood/complications ; *Leukocyte L1 Antigen Complex/blood ; Longitudinal Studies ; Olfaction Disorders/blood/diagnosis ; Prospective Studies ; }, abstract = {BACKGROUND: This longitudinal prospective study aims to investigate the potential of circulating calprotectin (cCLP) as a biomarker in persistent olfactory dysfunctions following COVID-19 infection.

METHODS: Thirty-six patients with persistent hyposmia or anosmia post COVID-19 were enrolled (HT0) and re-evaluated after three months of olfactory training (HT1). Two control groups included 18 subjects without olfactory defects post COVID-19 (CG1) and 18 healthy individuals (CG2). Nasal brushing of the olfactory cleft and blood collection were performed to assess circulating calprotectin levels.

RESULTS: Higher calprotectin levels were observed in serum and nasal supernatant of hyposmic patients (HT0) compared to control groups (CG1 and CG2). Post-olfactory training (HT1), olfactory function improved significantly, paralleled by decreased calprotectin levels in serum and nasal samples. Circulating calprotectin holds potential as a biomarker in persistent olfactory dysfunctions after COVID-19. The decrease in calprotectin levels post-olfactory training implies a role in monitoring and evaluating treatment responses.

DISCUSSION AND CONCLUSIONS: These findings contribute to the growing literature on potential biomarkers in post-COVID-19 olfactory dysfunctions and underscore the importance of investigating novel biomarkers for personalized patient management. Nevertheless, further studies are needed to validate the application of calprotectin assay in nasal diseases and its correlation with nasal cytology.}, } @article {pmid38962781, year = {2024}, author = {Schwartz, CE and Borowiec, K and Waldman, AH and Sutherland, T and Contreras, B and Abatan, E and Huang, IC and Rohde, G and Rapkin, BD and Skolasky, RL}, title = {Emerging priorities and concerns in the wake of the COVID-19 pandemic: qualitative and quantitative findings from a United States national survey.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1365657}, pmid = {38962781}, issn = {2296-2565}, support = {P01 AG066603/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Cross-Sectional Studies ; Male ; Female ; United States/epidemiology ; Middle Aged ; Adult ; *Quality of Life/psychology ; Surveys and Questionnaires ; Aged ; SARS-CoV-2 ; Pandemics ; }, abstract = {PURPOSE: The present study examines how the coronavirus disease 2019 (COVID-19) experience affected values and priorities.

METHODS: This cross-sectional study collected data between January and April 2023, from 1,197 individuals who are chronically ill or part of a general population sample. Using open-ended prompts and closed-ended questions, we investigated individuals' perceptions about COVID-19-induced changes in what quality of life means to them, what and who are important, life focus, and changes in norms and stressors. Data analyses included content and psychometric analysis, leading to latent profile analysis (LPA) to characterize distinct groups, and analysis of variance and chi-squared to compare profile groups' demographic characteristics.

RESULTS: About 75% of the study sample noted changes in values and/or priorities, particularly in the greater prominence of family and friends. LPA yielded a four-profile model that fit the data well. Profile 1 (Index group; 64% of the sample) had relatively average scores on all indicators. Profile 2 (COVID-Specific Health & Resignation to Isolation Attributable to COVID-19; 5%) represented COVID-19-specific preventive health behaviors along with noting the requisite isolation and disengagement entailed in the social distancing necessary for COVID-19 prevention. Profile 3 (High Stress, Low Trust; 25%) represented high multi-domain stress, with the most elevated scores both on focusing on being true to themselves and perceiving people to be increasingly uncivil. Profile 4 (Active in the World, Low Trust; 6%) was focused on returning to work and finding greater meaning in their activities. These groups differed on race, marital status, difficulty paying bills, employment status, number of times they reported having had COVID-19, number of COVID-19 boosters received, whether they had Long COVID, age, BMI, and number of comorbidities.

CONCLUSION: Three years after the beginning of the worldwide COVID-19 pandemic, its subjective impact is notable on most study participants' conceptualization of quality of life, priorities, perspectives on social norms, and perceived stressors. The four profile groups reflected distinct ways of dealing with the long-term effects of COVID-19.}, } @article {pmid38961833, year = {2024}, author = {Shigematsu, L and Kimura, R and Terai, H and Mimura, Y and Ito, D and Bun, S and Namkoong, H and Asakura, T and Chubachi, S and Masaki, K and Ohgino, K and Miyata, J and Kawada, I and Ishii, M and Takemura, R and Ueda, S and Yoshiyama, T and Kokuto, H and Kusumoto, T and Oashi, A and Miyawaki, M and Saito, F and Tani, T and Ishioka, K and Takahashi, S and Nakamura, M and Sato, Y and Fukunaga, K}, title = {Social impact of brain fog and analysis of risk factors: Long COVID in Japanese population.}, journal = {Annals of clinical and translational neurology}, volume = {11}, number = {8}, pages = {2188-2200}, pmid = {38961833}, issn = {2328-9503}, support = {JP 21fk0108431//Japan Agency for Medical Research and Development/ ; JP 21fk0108553//Japan Agency for Medical Research and Development/ ; JP 21fk0108563//Japan Agency for Medical Research and Development/ ; JP 21fk0108573//Japan Agency for Medical Research and Development/ ; JP 22fk0108510//Japan Agency for Medical Research and Development/ ; JP 22fk0108513//Japan Agency for Medical Research and Development/ ; JP 22fk0108573//Japan Agency for Medical Research and Development/ ; JP 22wm0325031//Japan Agency for Medical Research and Development/ ; JP20fk0108415//Japan Agency for Medical Research and Development/ ; JP20fk0108452//Japan Agency for Medical Research and Development/ ; JP20nk0101612//Japan Agency for Medical Research and Development/ ; 20CA2054//Ministry of Health, Labour and Welfare/ ; JPMH21HA2011//Ministry of Health, Labour and Welfare/ ; JPMH23HA2011//Ministry of Health, Labour and Welfare/ ; JPMJCR20H2//Core Research for Evolutional Science and Technology/ ; JPMJPR21R7//Precursory Research for Embryonic Science and Technology/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cohort Studies ; *COVID-19/epidemiology/psychology ; East Asian People ; Hospitalization/statistics & numerical data ; Japan/epidemiology ; Memory Disorders/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; *Mental Fatigue/virology ; }, abstract = {OBJECTIVE: To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID-19).

METHODS: We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID-19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration.

RESULTS: The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C-reactive protein and elevated D-dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores.

INTERPRETATIONS: This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.}, } @article {pmid38961771, year = {2024}, author = {de Souza, ITC and Dos Santos, EGG and da Costa, RVA and Ferreira, WDN and Santana, KJ and Felix, JVDS and Brandão, CBF and Candeia, AA and Nascimento, LMDS and da Silva, ACT and Ferreira, CAS and Queiroz, MHBS and Silva, JS and Lima, JHM and Pedrosa, R and Onofre, T and de França, EET}, title = {Effects of high-definition transcranial direct current stimulation combined with inspiratory muscle training for treating respiratory sequelae of long COVID: A case series.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {3}, pages = {e2109}, doi = {10.1002/pri.2109}, pmid = {38961771}, issn = {1471-2865}, mesh = {Humans ; Female ; Male ; *Breathing Exercises ; *COVID-19 ; Middle Aged ; Aged ; *Transcranial Direct Current Stimulation ; Adult ; *Respiratory Muscles/physiopathology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Treatment Outcome ; Muscle Strength/physiology ; Respiratory Function Tests ; }, abstract = {INTRODUCTION: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High-definition transcranial direct current stimulation (HD-tDCS) has been tested in patients with COVID-19; however, previous studies did not investigate the HD-tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID.

CASE PRESENTATION: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD-tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention.

HD-tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID.}, } @article {pmid38961383, year = {2024}, author = {Neu, F and Nay, S and Schuchardt, S and Klawonn, F and Skripuletz, T and Suehs, KW and Pessler, F}, title = {Targeted metabolomics identifies accurate CSF metabolite biomarkers for the differentiation between COVID-19 with neurological involvement and CNS infections with neurotropic viral pathogens.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {620}, pmid = {38961383}, issn = {1479-5876}, mesh = {Humans ; *COVID-19/cerebrospinal fluid/virology ; *Biomarkers/cerebrospinal fluid ; *Metabolomics/methods ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; Aged ; Adult ; Central Nervous System Infections/cerebrospinal fluid/virology ; Diagnosis, Differential ; }, abstract = {BACKGROUND: COVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis.

METHODS: To assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls.

RESULTS: Standard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0-12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation.

CONCLUSIONS: The results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.}, } @article {pmid38961009, year = {2024}, author = {Weigel, B and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S}, title = {Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {9}, pages = {2489-2507}, pmid = {38961009}, issn = {1573-2649}, support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Buxton Foundation/ ; 4879//Henty Community/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Fatigue Syndrome, Chronic/psychology ; *COVID-19/psychology/complications ; Male ; Female ; *Quality of Life ; Middle Aged ; Pilot Projects ; Adult ; Australia ; *SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; }, abstract = {PURPOSE: Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC.

METHODS: Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC.

RESULTS: Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants' SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001).

CONCLUSION: This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes.}, } @article {pmid38961007, year = {2024}, author = {Debie, Y and Palte, Z and Salman, H and Verbruggen, L and Vanhoutte, G and Chhajlani, S and Raats, S and Roelant, E and Vandamme, T and Peeters, M and van Dam, PA}, title = {Long-term effects of the COVID-19 pandemic for patients with cancer.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {10}, pages = {2845-2853}, pmid = {38961007}, issn = {1573-2649}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Male ; Female ; *Neoplasms/psychology ; *Quality of Life ; Middle Aged ; Aged ; *SARS-CoV-2 ; Surveys and Questionnaires ; Adult ; Anxiety ; Fatigue ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Pandemics ; }, abstract = {INTRODUCTION: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10-20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort.

METHODS: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection.

RESULTS: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes.

CONCLUSION: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve.}, } @article {pmid38960797, year = {2024}, author = {García-Meléndez, DD and Presa, RM and Castro, PQ and Calleja, BS and Calvo, SR and Morales-Casado, MI}, title = {Comparative imaging study of patients with persistent olfactory dysfunction due to mild COVID-19 using structural and functional MRI.}, journal = {Medicina clinica}, volume = {163}, number = {6}, pages = {286-290}, doi = {10.1016/j.medcli.2024.04.021}, pmid = {38960797}, issn = {1578-8989}, mesh = {Humans ; *Magnetic Resonance Imaging ; *COVID-19/complications/diagnostic imaging ; Adult ; Male ; *Olfaction Disorders/etiology/diagnostic imaging ; Female ; *Olfactory Bulb/diagnostic imaging/pathology ; Case-Control Studies ; Middle Aged ; Neuroimaging ; }, abstract = {INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging.

MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function.

RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively.

CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.}, } @article {pmid38960664, year = {2024}, author = {Pastorello, A and Meyer, L and Coste, J and Davisse-Paturet, C and de Lamballerie, X and Melchior, M and Novelli, S and Rahib, D and Bajos, N and Vuillermoz, C and Franck, JE and Manto, C and Rouquette, A and Warszawski, J and EpiCov Study Group, FT}, title = {Temporal changes in the risk of six-month post-covid symptoms: a national population-based cohort study.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwae174}, pmid = {38960664}, issn = {1476-6256}, abstract = {It is unclear how the risk of post-covid symptoms evolved during the pandemic, especially before the spread of Severe Acute Respiratory Syndrome Coronavirus 2 variants and the availability of vaccines. We used modified Poisson regressions to compare the risk of six-month post-covid symptoms and their associated risk factors according to the period of first acute covid: during the French first (March-May 2020) or second (September-November 2020) wave. Non-response weights and multiple imputation were used to handle missing data. Among participants aged 15 or more in a national population-based cohort, the risk of post-covid symptoms was 14.6% (95% CI: 13.9%, 15.3%) in March-May 2020, versus 7.0% (95% CI: 6.3%, 7.7%) in September-November 2020 (adjusted RR: 1.36, 95% CI: 1.20, 1.55). For both periods, the risk was higher in the presence of baseline physical condition(s), and it increased with the number of acute symptoms. During the first wave, the risk was also higher for women, in the presence of baseline mental condition(s), and it varied with educational level. In France in 2020, the risk of six-month post-covid symptoms was higher during the first than the second wave. This difference was observed before the spread of variants and the availability of vaccines.}, } @article {pmid38960014, year = {2024}, author = {Oscoz-Ochandorena, S and Legarra-Gorgoñon, G and García-Alonso, Y and García-Alonso, N and Izquierdo, M and Ramírez-Vélez, R}, title = {Reduced autonomic function in patients with long-COVID-19 syndrome is mediated by cardiorespiratory fitness.}, journal = {Current problems in cardiology}, volume = {49}, number = {9}, pages = {102732}, doi = {10.1016/j.cpcardiol.2024.102732}, pmid = {38960014}, issn = {1535-6280}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Heart Rate/physiology ; *Post-Acute COVID-19 Syndrome ; *Autonomic Nervous System/physiopathology ; SARS-CoV-2 ; Adult ; Case-Control Studies ; Exercise Tolerance/physiology ; Muscle Strength/physiology ; Autonomic Nervous System Diseases/physiopathology/diagnosis/etiology ; Oxygen Consumption/physiology ; }, abstract = {BACKGROUND: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity-mediated disruption of the ANS resulting particularly in exercise intolerance.

METHODS: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO2), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO2, and HRV indicators. Two-sided p < 0.05 was considered as significant.

RESULTS: The HRV parameters-RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2-were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO2 and RMSSD (mediation effect = 24.4%) as well as peak VO2 and SDNN (mediation effect = 25.1%) in the LCS patients.

CONCLUSIONS: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO2 observed in long COVID-19 patients.}, } @article {pmid38959327, year = {2024}, author = {Peluso, MJ and Ryder, D and Flavell, RR and Wang, Y and Levi, J and LaFranchi, BH and Deveau, TM and Buck, AM and Munter, SE and Asare, KA and Aslam, M and Koch, W and Szabo, G and Hoh, R and Deswal, M and Rodriguez, AE and Buitrago, M and Tai, V and Shrestha, U and Lu, S and Goldberg, SA and Dalhuisen, T and Vasquez, JJ and Durstenfeld, MS and Hsue, PY and Kelly, JD and Kumar, N and Martin, JN and Gambhir, A and Somsouk, M and Seo, Y and Deeks, SG and Laszik, ZG and VanBrocklin, HF and Henrich, TJ}, title = {Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.}, journal = {Science translational medicine}, volume = {16}, number = {754}, pages = {eadk3295}, pmid = {38959327}, issn = {1946-6242}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AI145806/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 NS136197/NS/NINDS NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/virology/pathology ; *RNA, Viral ; *SARS-CoV-2 ; *T-Lymphocytes/immunology ; Male ; Middle Aged ; Female ; *Lymphocyte Activation ; *Positron-Emission Tomography ; Adult ; Aged ; Lung/virology/pathology/diagnostic imaging ; Time Factors ; }, abstract = {The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [[18]F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [[18]F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.}, } @article {pmid38958890, year = {2024}, author = {Chikopela, T and Mwesigwa, N and Masenga, SK and Kirabo, A and Shibao, CA}, title = {The Interplay of HIV and Long COVID in Sub-Saharan Africa: Mechanisms of Endothelial Dysfunction.}, journal = {Current cardiology reports}, volume = {26}, number = {9}, pages = {859-871}, pmid = {38958890}, issn = {1534-3170}, support = {AHA 967054//American Heart Association/ ; }, mesh = {Humans ; *HIV Infections/physiopathology/complications/epidemiology ; *COVID-19/physiopathology/epidemiology/complications ; *Endothelium, Vascular/physiopathology ; Africa South of the Sahara/epidemiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Oxidative Stress ; Cardiovascular Diseases/physiopathology/epidemiology ; }, abstract = {PURPOSE OF REVIEW: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV.

RECENT FINDINGS: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region.}, } @article {pmid38958213, year = {2024}, author = {Müllenmeister, C and El-Sayed, I and Heinemann, S and Schröder, D and Müller, F and Hummers, E and Stölting, A and Happle, C and Dopfer-Jablonka, A and Marotzki, U and Schmachtenberg, T}, title = {Navigating uncertainty: occupational therapists' experiences of Long COVID management in Germany, Austria and Switzerland.}, journal = {Disability and rehabilitation}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/09638288.2024.2367603}, pmid = {38958213}, issn = {1464-5165}, abstract = {PURPOSE: Long COVID presents global challenges for healthcare professionals. Occupational therapists responded by seeking effective treatment strategies. The approaches of occupational therapists supporting long-haulers in German-speaking countries remain under-explored. The purpose of this study is to explore how occupational therapists in Germany, Austria and Switzerland navigate and apply profession-specific strategies in the new clinical landscape of Long COVID care.

MATERIALS AND METHODS: This study used qualitative-descriptive design and content analysis to extract insights from seven semi-structured interviews with occupational therapists in inpatient and outpatient settings from three countries.

RESULTS: Four overarching themes emerged: how Long COVID was encountered within the scope of occupational therapy, the multifaceted repertoire experts used to support long haulers, triumphs and challenges that emerged in Long COVID treatment, and recommendations and opportunities for occupational therapy practice. The results underscore the complex support needed for long-haulers, achieved through a multifaceted occupational therapy repertoire, incorporating client-centred, occupation-focused, and context-referencing strategies with shared decision-making and collaborative therapy planning.

CONCLUSIONS: Occupational therapy concepts, with their focus on human occupation, may offer new treatment options and strategies for managing emerging conditions such as Long COVID.}, } @article {pmid38958179, year = {2024}, author = {Maccarone, MC and Coraci, D and Regazzo, G and Masiero, S}, title = {Symptoms patterns and health-related quality of life in a real-life cohort of Long COVID patients: understanding the complexity to optimize the rehabilitation treatment.}, journal = {American journal of physical medicine & rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1097/PHM.0000000000002578}, pmid = {38958179}, issn = {1537-7385}, abstract = {OBJECTIVE: We wanted to identify prevalent symptoms and patterns of Long COVID syndrome, assess the impact on health-related quality of life, and explore factors linked to lower quality of life, including vaccination status and symptom count, in a real-life cohort.

DESIGN: observational retrospective study.

RESULTS: We assessed 133 patients and 85 completed the evaluations. The most common symptoms reported were motor deficit (95.29%) and fatigue (94.12%), while respiratory symptoms, cognitive deficits and weakness (76.47%) were less frequent. Many patients experienced multiple symptoms, with the majority reporting 5 to 8 symptoms simultaneously, most associated with fatigue. However, the number of symptoms did not correlate with health-related quality of life as measured by the 12-Item Short Form Survey (SF-12) questionnaire. Finally, vaccination status did not significantly affect SF-12 scores or the number of reported symptoms.

CONCLUSION: Our analysis highlighted the presence of diverse multisystemic symptoms in Long COVID patients. Many individuals experienced multiple associated symptoms, negatively affecting their overall quality of life. Neither vaccination status nor the number of symptoms appeared to influence reported quality of life. This emphasizes the need for a comprehensive, early, and multi-disciplinary approach to address the syndrome's diverse symptoms.}, } @article {pmid38954891, year = {2024}, author = {Le, GH and Kwan, ATH and Guo, Z and Teopiz, KM and Wong, S and Meshkat, S and d'Andrea, G and Ho, R and Rhee, TG and Cao, B and Badulescu, S and Phan, L and Rosenblat, JD and Mansur, RB and Subramaniapillai, M and McIntyre, RS}, title = {Impact of vortioxetine on depressive symptoms moderated by symptoms of anxiety in persons with post-COVID-19 condition: A secondary analysis.}, journal = {Psychiatry research}, volume = {339}, number = {}, pages = {116068}, doi = {10.1016/j.psychres.2024.116068}, pmid = {38954891}, issn = {1872-7123}, mesh = {Humans ; *Vortioxetine/pharmacology/therapeutic use ; Male ; Female ; Middle Aged ; *Anxiety/drug therapy ; *Depression/drug therapy/etiology ; Double-Blind Method ; Adult ; *COVID-19/complications/psychology ; Quality of Life ; Anxiety Disorders/drug therapy ; Aged ; Antidepressive Agents/therapeutic use/pharmacology ; }, abstract = {OBJECTIVE: Recovery from a COVID-19 infection can lead to post-COVID-19 condition (PCC), which causes a multitude of debilitating symptoms that negatively affect an individual's health-related quality of life, including depressive and anxiety symptoms. We aim to examine the mediatory effects of anxiety on depressive symptoms in persons with PCC receiving vortioxetine.

METHODS: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial investigating vortioxetine treatment on cognitive functioning in persons with PCC. Anxiety and depressive symptoms were measured by the 7-Item Generalized Anxiety Disorder (GAD-7) Scale and the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR-16), respectively.

RESULTS: Based on data of 147 participants, GAD-7 scores were significantly positively associated with QIDS-SR-16 scores (β=0.038, 95 % CI [0.029,0.047], p < 0.001). After adjusting for covariates, a significant group (χ[2]=176.786, p < 0.001), time (χ[2]=8.914, p = 0.003), and treatment x time x GAD-7 score interaction (χ[2]=236.483, p < 0.001) effect was observed. Vortioxetine-treated participants had a significant difference in overall change in depressive symptoms (mean difference=-3.15, SEM=0.642, 95 % CI [-4.40,-1.89], p < 0.001).

CONCLUSION: Anxiety symptoms were significantly associated with depressive symptoms in persons with PCC. Antidepressant efficacy on ameliorating depressive symptoms is dependent on improving anxiety symptoms, underscoring significant implications in improving treatment efficacy and patient quality of life.}, } @article {pmid38954717, year = {2024}, author = {Malambo, W and Chanda, D and Besa, L and Engamba, D and Mwiinga, L and Mwitumwa, M and Matibula, P and Naik, N and Sivile, S and Agolory, S and Auld, A and Mulenga, L and Hines, JZ and Fwoloshi, S}, title = {Clinical characteristics and factors associated with long COVID among post-acute COVID-19 clinic patients in Zambia, August 2020 to January 2023: A cross-sectional and longitudinal study design.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0306131}, pmid = {38954717}, issn = {1932-6203}, mesh = {Humans ; Zambia/epidemiology ; *COVID-19/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Longitudinal Studies ; Adult ; Middle Aged ; *SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; Aged ; Young Adult ; Adolescent ; Comorbidity ; Risk Factors ; Prevalence ; }, abstract = {INTRODUCTION: A number of seroprevalence studies in Zambia document the extent of spread of acute SARS-CoV-2 infection, yet knowledge gaps still exist on symptoms and conditions that continue or develop after acute COVID-19 (long COVID). This is an important gap given the estimated prevalence of long COVID in other African countries. We assessed factors associated with long COVID at the initial visit to a post-acute COVID-19 (PAC-19) clinic and longitudinally among a cohort of patients with ≥2 review visits.

METHODS: We implemented a cross-sectional and longitudinal analysis of PAC-19 clinic patients from Aug-2020 to Jan-2023. The study outcome was long COVID; defined as the presence of new, relapsing, or persistent COVID-19 symptoms that interfere with the ability to function at home or work. Explanatory variables were demographic and clinical characteristics of patients which included sex, age group, presence of new onset medical conditions, presence of pre-existing comorbidities, vaccination status and acute COVID-19 episode details. We fitted logistic and mixed effects regression models to assess for associated factors and considered statistical significance at p<0.05.

RESULTS: Out of a total 1,359 PAC-19 clinic patients in the cross-sectional analysis, 548 (40.3%) patients with ≥2 PAC-19 clinic visits were in the longitudinal analysis. Patients' median age was 53 (interquartile range [IQR]: 41-63) years, 919 (67.6%) were hospitalized for acute COVID-19, and of whom 686 (74.6%) had severe acute COVID-19. Overall, 377 (27.7%) PAC-19 clinic patients had long COVID. Patients with hospital length of stay ≥15 days (adjusted odds ratio [aOR]: 5.37; 95% confidence interval [95% CI]: 2.99-10.0), severe acute COVID-19 (aOR: 3.22; 95% CI: 1.68-6.73), and comorbidities (aOR:1.50; 95% CI: 1.02-2.21) had significantly higher chance of long COVID. Longitudinally, long COVID prevalence significantly (p<0.001) declined from 75.4% at the initial PAC-19 visit to 26.0% by the final visit. The median follow-up time was 7 (IQR: 4-12) weeks.

CONCLUSION: Factors associated with long COVID in Zambia were consistent both cross-sectionally at the initial visit to PAC-19 clinics and longitudinally across subsequent review visits. This highlights the importance of ongoing monitoring and tailored interventions for patients with comorbidities and severe COVID-19 to mitigate the long-term impacts of COVID-19.}, } @article {pmid38954402, year = {2024}, author = {Liao, S and Teopiz, KM and Kwan, ATH and Le, GH and Wong, S and Ballum, H and Rhee, TG and Badulescu, S and Cao, B and Guo, Z and Meshkat, S and Phan, L and Subramaniapillai, M and Ho, R and McIntyre, RS}, title = {Relationship between anhedonia and psychosocial functioning in post-COVID-19 condition: a post-hoc analysis.}, journal = {Current medical research and opinion}, volume = {40}, number = {8}, pages = {1407-1411}, doi = {10.1080/03007995.2024.2374510}, pmid = {38954402}, issn = {1473-4877}, mesh = {Humans ; Female ; Male ; *Anhedonia ; *COVID-19/psychology/complications ; *Psychosocial Functioning ; Middle Aged ; Adult ; Double-Blind Method ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {BACKGROUND: Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e. reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of individuals with PCC.

METHODS: This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption.

RESULTS: Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI).

DISCUSSIONS: Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.}, } @article {pmid38953987, year = {2024}, author = {Baldassarro, VA and Alastra, G and Cescatti, M and Quadalti, C and Lorenzini, L and Giardino, L and Calzà, L}, title = {SARS-CoV-2-related peptides induce endothelial-to-mesenchymal transition in endothelial capillary cells derived from different body districts: focus on membrane (M) protein.}, journal = {Cell and tissue research}, volume = {397}, number = {3}, pages = {241-262}, pmid = {38953987}, issn = {1432-0878}, support = {FISR2020IP_01778//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/virology/pathology ; *Endothelial Cells/metabolism/virology ; *Epithelial-Mesenchymal Transition ; Coronavirus M Proteins ; Spike Glycoprotein, Coronavirus/metabolism ; Peptides/pharmacology ; Lung/virology/pathology ; Human Umbilical Vein Endothelial Cells/metabolism ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19, may lead to multiple organ dysfunctions and long-term complications. The induction of microvascular dysfunction is regarded as a main player in these pathological processes. To investigate the possible impact of SARS-CoV-2-induced endothelial-to-mesenchymal transition (EndMT) on fibrosis in "long-COVID" syndrome, we used primary cultures of human microvascular cells derived from the lungs, as the main infection target, compared to cells derived from different organs (dermis, heart, kidney, liver, brain) and to the HUVEC cell line. To mimic the virus action, we used mixed SARS-CoV-2 peptide fragments (PepTivator[®]) of spike (S), nucleocapsid (N), and membrane (M) proteins. TGFβ2 and cytokine mix (IL-1β, IL-6, TNFα) were used as positive controls. The percentage of cells positive to mesenchymal and endothelial markers was quantified by high content screening. We demonstrated that S+N+M mix induces irreversible EndMT in all analyzed endothelial cells via the TGFβ pathway, as demonstrated by ApoA1 treatment. We then tested the contribution of single peptides in lung and brain cells, demonstrating that EndMT is triggered by M peptide. This was confirmed by transfection experiment, inducing the endogenous expression of the glycoprotein M in lung-derived cells. In conclusion, we demonstrated that SARS-CoV-2 peptides induce EndMT in microvascular endothelial cells from multiple body districts. The different peptides play different roles in the induction and maintenance of the virus-mediated effects, which are organ-specific. These results corroborate the hypothesis of the SARS-CoV-2-mediated microvascular damage underlying the multiple organ dysfunctions and the long-COVID syndrome.}, } @article {pmid38951002, year = {2024}, author = {Burton, A and Bone, JK and Lawrence-Lunniss, K and Philip, KE}, title = {Acceptability and feasibility of a theatre-based wellness programme to support people living with long COVID: a single-arm feasibility study.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e083224}, pmid = {38951002}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/psychology ; *Feasibility Studies ; Male ; Female ; Middle Aged ; Aged ; *Quality of Life ; *Health Promotion/methods ; *SARS-CoV-2 ; Drama ; Loneliness/psychology ; Patient Acceptance of Health Care/psychology ; Adult ; Social Support ; }, abstract = {OBJECTIVES: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and well-being of people with long COVID.

DESIGN: Single-group, repeated-measures feasibility study.

SETTING: Community centre and online.

PARTICIPANTS: Adults with diagnosed long COVID experiencing breathlessness, pain and/or loneliness.

INTERVENTION: Six-week participatory creative programme delivered to one online and one in-person group facilitated by movement, voice and drama consultants using breathing, visualisation, singing, poetry, storytelling and movement exercises.

PRIMARY OUTCOME MEASURES: Programme acceptability and feasibility measured via uptake, reasons for non-attendance and barriers to engagement.

SECONDARY OUTCOME MEASURES: Feasibility of recruitment and data collection procedures measured through proportion of missing data and follow-up rates, mechanisms of action of the programme identified through qualitative interviews, changes in mental health, well-being, quality of life, loneliness, social support, fatigue, breathlessness and post-COVID-19 functional status at 8-week follow-up.

RESULTS: 21 people expressed interest in participating, 20 people took part in the programme, 19 completed baseline and 16 completed follow-up assessments. Participants attended an average of 4.8 of 6 sessions (SD=1.5, range 2-6). Exploratory analyses demonstrated significant improvements in self-rated health (t-test mean difference=0.12, 95% CI=0.00, 0.23, p=0.04) and chronic fatigue symptoms (mean difference=-3.50, 95% CI=-6.97, -0.03, p=0.05) at 8 weeks. Key mechanisms of action that supported health and well-being included: increased sense of community, illness acceptance, experiencing joy, increased confidence in managing everyday life, increased ability to relax and reconnection with previous identity. Barriers to engagement included: activities being outside of the participant's comfort zone, ongoing long COVID symptoms, emotional consequences of sharing experiences and connectivity and connecting online.

CONCLUSIONS: A 6-week theatre-based programme was perceived as acceptable to most participants and resulted in some positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development and scale-up of this and related arts programmes to support people living with long COVID.}, } @article {pmid38948732, year = {2024}, author = {Hamlin, RE and Pienkos, SM and Chan, L and Stabile, MA and Pinedo, K and Rao, M and Grant, P and Bonilla, H and Holubar, M and Singh, U and Jacobson, KB and Jagannathan, P and Maldonado, Y and Holmes, SP and Subramanian, A and Blish, CA}, title = {Sex differences and immune correlates of Long COVID development, persistence, and resolution.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38948732}, issn = {2692-8205}, support = {K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI076614/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; T32 AI007502/AI/NIAID NIH HHS/United States ; T32 AI007290/AI/NIAID NIH HHS/United States ; }, abstract = {Sex differences have been observed in acute COVID-19 and Long COVID (LC) outcomes, with greater disease severity and mortality during acute infection in males and a greater proportion of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to the pathogenesis of LC. To investigate the immunologic underpinnings of LC development and persistence, we used single-cell transcriptomics, single-cell proteomics, and plasma proteomics on blood samples obtained during acute SARS-CoV-2 infection and at 3 and 12 months post-infection in a cohort of 45 patients who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Specifically, males who would develop LC at 3 months had widespread increases in TGF-β signaling during acute infection in proliferating NK cells. Females who would develop LC demonstrated increased expression of XIST, an RNA gene implicated in autoimmunity, and increased IL1 signaling in monocytes at 12 months post infection. Several immune features of LC were also conserved across sexes. Both males and females with LC had reduced co-stimulatory signaling from monocytes and broad upregulation of NF-κB transcription factors. In both sexes, those with persistent LC demonstrated increased LAG3, a marker of T cell exhaustion, reduced ETS1 transcription factor expression across lymphocyte subsets, and elevated intracellular IL-4 levels in T cell subsets, suggesting that ETS1 alterations may drive an aberrantly elevated Th2-like response in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics.}, } @article {pmid38947233, year = {2024}, author = {Dietz, TK and Brondstater, KN}, title = {Long COVID management: a mini review of current recommendations and underutilized modalities.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1430444}, pmid = {38947233}, issn = {2296-858X}, abstract = {Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.}, } @article {pmid38947091, year = {2024}, author = {Santos Guedes de Sa, K and Silva, J and Bayarri-Olmos, R and Brinda, R and Alec Rath Constable, R and Colom Diaz, PA and Kwon, DI and Rodrigues, G and Wenxue, L and Baker, C and Bhattacharjee, B and Wood, J and Tabacof, L and Liu, Y and Putrino, D and Horvath, TL and Iwasaki, A}, title = {A causal link between autoantibodies and neurological symptoms in long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38947091}, support = {R01 AI157488/AI/NIAID NIH HHS/United States ; }, abstract = {Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.}, } @article {pmid38947087, year = {2024}, author = {O'Neil, ST and Madlock-Brown, C and Wilkins, KJ and McGrath, BM and Davis, HE and Assaf, GS and Wei, H and Zareie, P and French, ET and Loomba, J and McMurry, JA and Zhou, A and Chute, CG and Moffitt, RA and Pfaff, ER and Yoo, YJ and Leese, P and Chew, RF and Lieberman, M and Haendel, MA}, title = {Finding Long-COVID: Temporal Topic Modeling of Electronic Health Records from the N3C and RECOVER Programs.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38947087}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UM1 TR004360/TR/NCATS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.}, } @article {pmid38947041, year = {2024}, author = {Quan, SF and Weaver, MD and Czeisler, MÉ and Barger, LK and Booker, LA and Howard, ME and Jackson, ML and Lane, RI and McDonald, CF and Ridgers, A and Robbins, R and Varma, P and Wiley, JF and Rajaratnam, SMW and Czeisler, CA}, title = {Sleep and long COVID: Preexisting sleep issues and the risk of PASC in a large general population using 3 different model definitions.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38947041}, support = {K01 HL150339/HL/NHLBI NIH HHS/United States ; R01 OH011773/OH/NIOSH CDC HHS/United States ; R56 HL151637/HL/NHLBI NIH HHS/United States ; }, abstract = {STUDY OBJECTIVES: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

METHODS: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC.

RESULTS: Prevalence rates of PASC among previously COVID-19 infected participants for three definitions of PASC were COPE (21.9%), NICE (38.9%) and RECOVER PASC Score (15.3%). PASC was associated with insomnia in all 3 models in fully adjusted models with adjusted odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models.

CONCLUSIONS: Insomnia, poor sleep quality and short sleep duration are potential risk factors for PASC. Interventions to improve sleep may decrease the development of PASC.}, } @article {pmid38947026, year = {2024}, author = {Wang, F and Zang, C and Li, H and Khullar, D and Zhang, Y and Strobel, S and Chen, Y and Sala, M and Patel, P and Comellas, A and Wylam, A and Weiner, M and Forrest, C and Carton, T and Kaushal, R}, title = {Real-World Effectiveness of Nirmatrelvir in Protecting Long COVID for Outpatient Adult Patients - A Large-Scale Observational Cohort Study from the RECOVER Initiative.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38947026}, issn = {2693-5015}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.}, } @article {pmid38945306, year = {2024}, author = {Shafqat, A and Masters, MC and Tripathi, U and Tchkonia, T and Kirkland, JL and Hashmi, SK}, title = {Long COVID as a disease of accelerated biological aging: An opportunity to translate geroscience interventions.}, journal = {Ageing research reviews}, volume = {99}, number = {}, pages = {102400}, doi = {10.1016/j.arr.2024.102400}, pmid = {38945306}, issn = {1872-9649}, mesh = {Humans ; *COVID-19 ; *Aging ; SARS-CoV-2 ; Geroscience ; Post-Acute COVID-19 Syndrome ; }, abstract = {It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the quality of life of an increasing number of COVID-19 survivors without any approved therapy and a paucity of clinical trials addressing its biological root causes. Notably, many of the symptoms of long COVID are typically seen with advancing age. Leveraging this similarity, we posit that Geroscience-which aims to target the biological drivers of aging to prevent age-associated conditions as a group-could offer promising therapeutic avenues for long COVID. Bearing this in mind, this review presents a translational framework for studying long COVID as a state of effectively accelerated biological aging, identifying research gaps and offering recommendations for future preclinical and clinical studies.}, } @article {pmid38944141, year = {2024}, author = {Joyce, MKP and Uchendu, S and Arnsten, AFT}, title = {Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control.}, journal = {Biological psychiatry}, volume = {}, number = {}, pages = {}, pmid = {38944141}, issn = {1873-2402}, support = {R01 MH130538/MH/NIMH NIH HHS/United States ; RF1 AG083090/AG/NIA NIH HHS/United States ; }, abstract = {Most mental disorders involve dysfunction of the dorsolateral prefrontal cortex (dlPFC), a recently evolved brain region that subserves working memory, abstraction, and the thoughtful regulation of attention, action, and emotion. For example, schizophrenia, depression, long COVID, and Alzheimer's disease are all associated with dlPFC dysfunction, with neuropathology often being focused in layer III. The dlPFC has extensive top-down projections, e.g., to the posterior association cortices to regulate attention and to the subgenual cingulate cortex via the rostral and medial PFC to regulate emotional responses. However, the dlPFC is particularly dependent on arousal state and is very vulnerable to stress and inflammation, which are etiological and/or exacerbating factors for most mental disorders. The cellular mechanisms by which stress and inflammation impact the dlPFC are a topic of current research and are summarized in this review. For example, the layer III dlPFC circuits that generate working memory-related neuronal firing have unusual neurotransmission, depending on NMDA receptor and nicotinic α7 receptor actions that are blocked under inflammatory conditions by kynurenic acid. These circuits also have unusual neuromodulation, with the molecular machinery to magnify calcium signaling in spines needed to support persistent firing, which must be tightly regulated to prevent toxic calcium actions. Stress rapidly weakens layer III connectivity by driving feedforward calcium-cAMP (cyclic adenosine monophosphate) opening of potassium channels on spines. This is regulated by postsynaptic noradrenergic α2A adrenergic receptor and mGluR3 (metabotropic glutamate receptor 3) signaling but dysregulated by inflammation and/or chronic stress exposure, which contribute to spine loss. Treatments that strengthen the dlPFC via pharmacological (the α2A adrenergic receptor agonist, guanfacine) or repetitive transcranial magnetic stimulation manipulation provide a rational basis for therapy.}, } @article {pmid38944016, year = {2024}, author = {Zülke, AE and Luppa, M and Wirkner, K and Reusche, M and Sander, C and Büchner, R and Schomerus, G and Then Bergh, F and Lehmann, J and Witte, AV and Villringer, A and Zeynalova, S and Löffler, M and Engel, C and Riedel-Heller, SG}, title = {Cognitive performance in adults with post-COVID syndrome: Results from a German case-control study.}, journal = {Journal of psychiatric research}, volume = {176}, number = {}, pages = {377-383}, doi = {10.1016/j.jpsychires.2024.06.036}, pmid = {38944016}, issn = {1879-1379}, mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/complications ; Germany/epidemiology ; Case-Control Studies ; *Cognitive Dysfunction/etiology/physiopathology ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Neuropsychological Tests ; Depression/epidemiology/etiology ; }, abstract = {Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (Mage: 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings.}, } @article {pmid38943790, year = {2024}, author = {Casula, EP and Esposito, R and Dezi, S and Ortelli, P and Sebastianelli, L and Ferrazzoli, D and Saltuari, L and Pezzopane, V and Borghi, I and Rocchi, L and Ajello, V and Trinka, E and Oliviero, A and Koch, G and Versace, V}, title = {Reduced TMS-evoked EEG oscillatory activity in cortical motor regions in patients with post-COVID fatigue.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {165}, number = {}, pages = {26-35}, doi = {10.1016/j.clinph.2024.06.008}, pmid = {38943790}, issn = {1872-8952}, mesh = {Humans ; *Transcranial Magnetic Stimulation/methods ; *COVID-19/physiopathology/complications ; Male ; Female ; *Motor Cortex/physiopathology ; Middle Aged ; *Fatigue/physiopathology/etiology ; *Electroencephalography/methods ; Adult ; *Evoked Potentials, Motor/physiology ; Beta Rhythm/physiology ; Aged ; }, abstract = {OBJECTIVE: Persistent fatigue is a major symptom of the so-called 'long-COVID syndrome', but the pathophysiological processes that cause it remain unclear. We hypothesized that fatigue after COVID-19 would be associated with altered cortical activity in premotor and motor regions.

METHODS: We used transcranial magnetic stimulation combined with EEG (TMS-EEG) to explore the neural oscillatory activity of the left primary motor area (l-M1) and supplementary motor area (SMA) in a group of sixteen post-COVID patients complaining of lingering fatigue as compared to a sample of age-matched healthy controls. Perceived fatigue was assessed with the Fatigue Severity Scale (FSS) and Fatigue Rating Scale (FRS).

RESULTS: Post-COVID patients showed a remarkable reduction of beta frequency in both areas. Correlation analysis exploring linear relation between neurophysiological and clinical measures revealed a significant inverse correlation between the individual level of beta oscillations evoked by TMS of SMA with the individual scores in the FRS (r(15) = -0.596; p = 0.012).

CONCLUSIONS: Post-COVID fatigue is associated with a reduction of TMS-evoked beta oscillatory activity in SMA.

SIGNIFICANCE: TMS-EEG could be used to identify early alterations of cortical oscillatory activity that could be related to the COVID impact in central fatigue.}, } @article {pmid38943168, year = {2024}, author = {Ramírez-Toscano, Y and Torres-Ibarra, L and Carnalla, M and Basto-Abreu, A and Vidaña-Perez, D and Colchero, MA and Bautista-Arredondo, S and Saydah, S and Barrientos-Gutiérrez, T}, title = {Prevalence of Post-COVID conditions among Mexican COVID-19 survivors: a nationwide cross-sectional study.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1729}, pmid = {38943168}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology ; Mexico/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; Prevalence ; Aged ; *Survivors/statistics & numerical data ; Young Adult ; Hypertension/epidemiology ; Adolescent ; Diabetes Mellitus, Type 2/epidemiology ; Sociodemographic Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: There are limited population-representative data that describe the potential burden of Post-COVID conditions (PCC) in Mexico. We estimated the prevalence of PCC overall and by sociodemographic characteristics among a representative sample of adults previously diagnosed with COVID-19 in Mexico. We additionally, characterized the PCC symptoms, and estimated the association between diagnosed type-2 diabetes and hypertension with PCC.

METHODS: We used data from the 2021 National Health and Nutrition Survey in Mexico, a nationally and regionally representative survey, from August 1st to October 31st, 2021. Using the WHO definition, we estimated the prevalence of PCC by sociodemographics and prevalence of PCC symptoms. We fit multivariable log-binomial regression models to estimate the associations.

RESULTS: The prevalence of PCC was 37.0%. The most common persistent symptoms were fatigue (56.8%), myalgia or arthralgia (47.5%), respiratory distress and dyspnea (42.7%), headache (34.0%), and cough (25.7%). The prevalence was higher in older people, women, and individuals with low socioeconomic status. There was no significant association between hypertension and PCC or diabetes and PCC prevalence.

CONCLUSIONS: About one-third of the adult Mexican population who had COVID-19 in 2021 had Post-COVID conditions. Our population-based estimates can help assess potential priorities for PCC-related health services, which is critical in light of our weak health system and limited funding.}, } @article {pmid38942167, year = {2024}, author = {Dashtban, A and Mizani, MA and Pasea, L and Tomlinson, C and Mu, Y and Islam, N and Rafferty, S and Warren-Gash, C and Denaxas, S and Horstmanshof, K and Kontopantelis, E and Petersen, S and Sudlow, C and Khunti, K and Banerjee, A and , }, title = {Vaccinations, cardiovascular drugs, hospitalization, and mortality in COVID-19 and Long COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {146}, number = {}, pages = {107155}, doi = {10.1016/j.ijid.2024.107155}, pmid = {38942167}, issn = {1878-3511}, mesh = {Humans ; *Hospitalization/statistics & numerical data ; *COVID-19/mortality/prevention & control/epidemiology ; Aged ; Male ; Middle Aged ; Female ; *Cardiovascular Diseases/mortality/prevention & control ; Adult ; *COVID-19 Vaccines/administration & dosage ; England/epidemiology ; *SARS-CoV-2 ; *Vaccination ; Aged, 80 and over ; Adolescent ; Young Adult ; *Cardiovascular Agents/therapeutic use ; Child, Preschool ; Child ; Infant ; Influenza, Human/mortality/prevention & control/epidemiology ; Infant, Newborn ; Influenza Vaccines/administration & dosage ; Risk Factors ; }, abstract = {OBJECTIVE: To identify highest-risk subgroups for COVID-19 and Long COVID(LC), particularly in contexts of influenza and cardiovascular disease(CVD).

METHODS: Using national, linked electronic health records for England (NHS England Secure Data Environment via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals (of all ages) with COVID-19 and LC (2020-2023). We compared all-cause hospitalization and mortality by prior CVD, high CV risk, vaccination status (COVID-19/influenza), and CVD drugs, investigating impact of vaccination and CVD prevention using population preventable fractions.

RESULTS: Hospitalization and mortality were 15.3% and 2.0% among 17,373,850 individuals with COVID-19 (LC rate 1.3%), and 16.8% and 1.4% among 301,115 with LC. Adjusted risk of mortality and hospitalization were reduced with COVID-19 vaccination ≥ 2 doses(COVID-19:HR 0.36 and 0.69; LC:0.44 and 0.90). With influenza vaccination, mortality was reduced, but not hospitalization (COVID-19:0.86 and 1.01, and LC:0.72 and 1.05). Mortality and hospitalization were reduced by CVD prevention in those with CVD, e.g., anticoagulants- COVID:19:0.69 and 0.92; LC:0.59 and 0.88; lipid lowering- COVID-19:0.69 and 0.86; LC:0.68 and 0.90. COVID-19 vaccination averted 245044 of 321383 and 7586 of 8738 preventable deaths after COVID-19 and LC, respectively.

INTERPRETATION: Prior CVD and high CV risk are associated with increased hospitalization and mortality in COVID-19 and LC. Targeted COVID-19 vaccination and CVD prevention are priority interventions.

FUNDING: NIHR. HDR UK.}, } @article {pmid38941608, year = {2024}, author = {Malireddi, RKS and Sharma, BR and Kanneganti, TD}, title = {Innate Immunity in Protection and Pathogenesis During Coronavirus Infections and COVID-19.}, journal = {Annual review of immunology}, volume = {42}, number = {1}, pages = {615-645}, pmid = {38941608}, issn = {1545-3278}, support = {R35 CA253095/CA/NCI NIH HHS/United States ; R01 AI101935/AI/NIAID NIH HHS/United States ; R01 AI124346/AI/NIAID NIH HHS/United States ; R37 AI101935/AI/NIAID NIH HHS/United States ; R01 AI160179/AI/NIAID NIH HHS/United States ; R01 AR056296/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Immunity, Innate ; *COVID-19/immunology ; *SARS-CoV-2/immunology/physiology ; Cytokine Release Syndrome/immunology ; Cytokines/metabolism ; Animals ; Coronavirus Infections/immunology/virology/prevention & control ; Immune Evasion ; }, abstract = {The COVID-19 pandemic was caused by the recently emerged β-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.}, } @article {pmid38941308, year = {2024}, author = {Kabir, MF and Nyein Yin, K and Htwe, O and Saffree Jeffree, M and Binti Ahmedy, F and Faizal Zainudin, M and Jahan, S and Hossain, MZ and Hossain, KMA and Islam, MW and Hossain, T}, title = {Symptom response and episodic disability of long COVID in people with spinal cord injury: A case-control study.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0304824}, pmid = {38941308}, issn = {1932-6203}, mesh = {Humans ; *Spinal Cord Injuries/complications/epidemiology ; Male ; Female ; *COVID-19/complications/epidemiology ; Case-Control Studies ; Adult ; Middle Aged ; Bangladesh/epidemiology ; *Disabled Persons ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal, cardiovascular and respiratory complications.

PURPOSE: This study aimed to identify the symptom responses and disease burden of long COVID in individuals with spinal cord injury.

METHODS: This case-control study was conducted on patients with SCI residing at a specialised rehabilitation centre in Bangladesh. Forty patients with SCI with and without long COVID symptoms (LCS) were enrolled in this study at a 1:1 ratio according to WHO criteria.

RESULT: Twelve LCS were observed in patients with SCI, including fatigue, musculoskeletal pain, memory loss, headache, respiratory problems, anxiety, depression, insomnia, problem in ADL problem in work, palpitation, and weakness. The predictors of developing long COVID include increasing age (p<0.002), increasing BMI (p<0.03), and longer duration of spinal cord injury (p<0.004). A significant difference (p<0.01) in overall years of healthy life lost due to disability (YLD) for non-long COVID cases was 2.04±0.596 compared to long COVID (LC) cases 1.22±2.09 was observed.

CONCLUSION: Bangladeshi patients of SCI presented 12 long COVID symptoms and have a significant disease burden compared to non long COVID cases.}, } @article {pmid38940402, year = {2024}, author = {Onay, ZR and Oksay, SC and Mavi Tortop, D and Bilgin, G and Ayhan, Y and Durankus, F and Girit, S}, title = {Impact of Long COVID on Lung Function in Children.}, journal = {Medeniyet medical journal}, volume = {39}, number = {2}, pages = {74-84}, pmid = {38940402}, issn = {2149-2042}, abstract = {OBJECTIVE: While the coronavirus disease-2019 (COVID-19) pandemic has generally resulted in milder illness among children than adults, persistent respiratory symptoms have been increasingly reported in this population.

METHODS: We conducted a prospective, single-center cohort study focusing on children experiencing prolonged respiratory symptoms after contracting COVID-19. Spirometry, 6- minute walk tests (6MWTs), and tests of lung volume, the diffusing capacity of the lungs for carbon monoxide (DLCO), and fractional exhaled nitric oxide (FeNO) were performed on COVID-19 survivors at least 4 weeks after infection and a group of healthy control subjects.

RESULTS: Fifty-five children with long-term COVID and 55 healthy control subjects were recruited. The weight, height, and body mass index Z-scores were similar in the groups. Within a median duration of 85 days (minimummaximum: 35-194) following COVID-19 infection, a restrictive pattern was observed to be more common in the study group (p=0.021). In children with long COVID, 6MWT distances, DLCO Z-scores, and the predicted values of spirometry and lung volume tests were found to be significantly lower but in the normal range. The average predicted values for DLCO, FeNO, and 6MWT were similar in the two groups.

CONCLUSIONS: Prolonged respiratory symptoms often persist long after COVID-19 infection, necessitating comprehensive evaluation of affected children. Close monitoring, including spirometry and lung volume assessments, is crucial for children with abnormalities in lung imaging. However, FeNO measurements were found to be ineffective in monitoring long COVID.}, } @article {pmid38940108, year = {2024}, author = {Gerkowicz, A and Bartosińska, J and Krakowski, P and Karpiński, R and Krasowska, D and Raczkiewicz, D and Kwasny, M and Krasowska, D}, title = {Red LED light therapy for telogen effluvium in the course of long COVID in patients with and without androgenetic alopecia.}, journal = {Annals of agricultural and environmental medicine : AAEM}, volume = {31}, number = {2}, pages = {239-247}, doi = {10.26444/aaem/177238}, pmid = {38940108}, issn = {1898-2263}, mesh = {Humans ; *Alopecia/radiotherapy/etiology/therapy ; Retrospective Studies ; Female ; Middle Aged ; *COVID-19/complications ; Male ; Adult ; SARS-CoV-2 ; Low-Level Light Therapy/methods ; Aged ; Hair/radiation effects ; Treatment Outcome ; Phototherapy/methods ; }, abstract = {INTRODUCTION AND OBJECTIVE: Photobiomodulation with the use of light-emitting diodes (LEDs) seems to be a promising option for long COVID. This retrospective study evaluates the efficiency of LED irradiation in the treatment of TE in the course of long COVID in patients with and without androgenetic alopecia.

MATERIAL AND METHODS: A retrospective single-centre chart review of patients with post-COVID hair loss was performed. 140 patients enrolled to the study were divided into four groups depending on the type of alopecia and treatment: 1) telogen effluvium with LED therapy (TE LED+), 2) telogen effluvium without LED therapy (TE LED-), 3) telogen effluvium and androgenetic alopecia with LED therapy (TE+AGA LED+), and 4) telogen effluvium and androgenetic alopecia without LED therapy (TE+AGA LED-). Clinical and trichoscopic parameters were compared.

RESULTS: After 12 weeks, cessation of hair loss and a negative hair pull test were more common in TE LED+ and TE+AGA LED+ in comparison to the patients without LED therapy (p<0.001, p=0.035, respectively). An increased number of thick hairs and an increased number of hairs within follicular units were more common in patients treated with LED irradiation, regardless of the type of alopecia, compared to the patients without LED therapy.

CONCLUSIONS: The study revealed that LED therapy is safe, well tolerated and seems to be a promising therapeutic option for TE in patients with long COVID. It can be used as adjuvant therapy leading to faster reduction of hair loss, enhancing hair regrowth as well as hair shaft thickness and density.}, } @article {pmid38939436, year = {2023}, author = {Chahal, CAA and Siripanthong, B}, title = {The Risk of Cardiovascular Sequelae in Post-Acute COVID-19: Comorbidity or COVID?.}, journal = {JACC. Advances}, volume = {2}, number = {6}, pages = {100455}, pmid = {38939436}, issn = {2772-963X}, } @article {pmid38938823, year = {2024}, author = {Kozor, R and Khor, L}, title = {No Coronary Microvascular Dysfunction After Mild COVID-19 Infection: So What Causes Long COVID Cardiac Symptoms?.}, journal = {JACC. Advances}, volume = {3}, number = {3}, pages = {100837}, pmid = {38938823}, issn = {2772-963X}, } @article {pmid38937639, year = {2024}, author = {Qian, J and Zhang, G and Wu, H and Sha, L}, title = {Impact of the COVID-19 infection on children with allergic diseases in China.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {38937639}, issn = {1530-0447}, abstract = {BACKGROUND: The COVID-19 pandemic has prompted investigations into the association between this novel virus and allergic diseases, particularly asthma in children. However, the nature of this relationship remains poorly established.

OBJECTIVE: This study aims to determine the clinical characteristics of children with allergic diseases who have contracted COVID-19.

METHODS: A retrospective study was conducted at the Children's Hospital Affiliated to the Capital Institute of Pediatrics from January to March 2023. A total of 568 children aged 0-17 years diagnosed with asthma and COVID-19 infection were included. A comparative analysis of clinical characteristics was conducted between asthma and non-asthma groups.

RESULTS: Asthmatic children with COVID-19 infection showed significantly higher frequencies of cough, wheezing, expectoration, and long-term symptoms compared to those without asthma (P < 0.05). Subgroups with poor therapy compliance exhibited elevated proportions of cough, chest tightness, and wheezing compared to good therapy compliance (P < 0.05). Multivariate logistic regression identified poor therapy compliance as a risk factor for long COVID in asthmatic children.

CONCLUSION: Children with asthma secondary to COVID-19 infection were more prone to developing coughs, expectoration, and wheezing. Poor therapy compliance emerged as a significant risk factor for long COVID-19 in these individuals.

IMPACT: Asthmatic children with COVID-19 infection showed significantly higher frequencies of cough, wheezing, expectoration. Poor therapy compliance was the risk factor for long COVID in asthmatic children. This article supplements the effects of different therapeutic drugs on the condition of children with asthma after infection with COVID-19 as well as the possible risk factors for the long COVID. The results of our study have important implications for public health policy makers and healthcare professionals. To understand the impact of COVID-19 on children with asthma will help guide appropriate management strategies and ensure access to necessary healthcare resources.}, } @article {pmid38936655, year = {2024}, author = {Choi, YJ and Kim, HN and Lee, J and Nham, E and Seong, H and Yoon, JG and Noh, JY and Song, JY and Cheong, HJ and Kim, WJ}, title = {Erythema nodosum as an unusual skin manifestation of long COVID: A case report.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {146}, number = {}, pages = {107152}, doi = {10.1016/j.ijid.2024.107152}, pmid = {38936655}, issn = {1878-3511}, mesh = {Humans ; *Erythema Nodosum/diagnosis/etiology/drug therapy ; Female ; Middle Aged ; *COVID-19/complications/diagnosis ; *SARS-CoV-2 ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Post-Acute COVID-19 Syndrome ; Skin/pathology/virology ; }, abstract = {Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.}, } @article {pmid38936427, year = {2024}, author = {Llana, T and Garces-Arilla, S and Juan, MC and Mendez-Lopez, M and Mendez, M}, title = {An immersive virtual reality-based object-location memory task reveals spatial long-term memory alterations in Long-COVID.}, journal = {Behavioural brain research}, volume = {471}, number = {}, pages = {115127}, doi = {10.1016/j.bbr.2024.115127}, pmid = {38936427}, issn = {1872-7549}, mesh = {Humans ; *Virtual Reality ; Male ; Female ; *COVID-19 ; Middle Aged ; *Spatial Memory/physiology ; *Memory, Long-Term/physiology ; Adult ; Neuropsychological Tests ; Aged ; Memory Disorders/etiology ; }, abstract = {Object-location memory (OLM) is a type of declarative memory for spatial information and consists of the individual's ability to establish accurate associations between objects and their spatial locations. Long-COVID describes the long-term effects of the COVID-19 disease. Long-COVID patients show medial temporal lobe dysfunction and neuropsychological alterations affecting memory. This study aimed to assess OLM in a group of Long-COVID patients, n=66, and a Control group of healthy individuals with similar age and sex composition, n=21, using an immersive virtual reality (iVR)-based OLM task. We also explored associations between the performance in the iVR-based OLM task and general cognitive function (MoCA), and both verbal (VSTM) and visuospatial (SSTM) span. The Long-COVID group showed fewer correct responses, made more task attempts, and invested more time in the iVR-based OLM task than the Control group. Delayed memory was more severely altered than immediate memory in Long-COVID participants. Better MoCA scores of the Long-COVID group were strongly associated with shorter times to complete the immediate recall of the iVR-based OLM task. Besides, the months elapsed since the COVID-19 infection were slightly associated with fewer correct responses in the immediate and 24-hour recalls. These results corroborate previous findings of memory alterations in the Long-COVID syndrome using an iVR-based OLM task, adding new evidence on spatial memory and long-term memory in this population. Implementing spatial iVR tasks to clinical research may improve our understanding of neuropsychological disorders.}, } @article {pmid38936313, year = {2024}, author = {Gomes-Neto, M and Almeida, KO and Correia, HF and Santos, JC and Gomes, VA and Serra, JPC and Durães, AR and Carvalho, VO}, title = {Determinants of cardiorespiratory fitness measured by cardiopulmonary exercise testing in COVID-19 survivors: a systematic review with meta-analysis and meta‑regression.}, journal = {Brazilian journal of physical therapy}, volume = {28}, number = {4}, pages = {101089}, pmid = {38936313}, issn = {1809-9246}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; *COVID-19/physiopathology ; *Exercise Test/methods ; Oxygen Consumption/physiology ; SARS-CoV-2 ; *Survivors ; }, abstract = {BACKGROUND: The relationship between cardiorespiratory fitness and its possible determinants in post-COVID-19 survivors has not been systematically assessed.

OBJECTIVES: To identify and summarize studies comparing cardiorespiratory fitness measured by cardiopulmonary exercise testing in COVID-19 survivors versus non-COVID-19 controls, as well as to determine the influence of potential moderating factors.

METHODS: We conducted a systematic search of MEDLINE/PubMed, Cochrane Library, EMBASE, Google Scholar, and SciELO since their inceptions until June 2022. Mean differences (MD), standard mean differences (SMD), and 95% confidence intervals (CI) were calculated. Subgroup and meta-regression analyses were used to evaluate potential moderating factors.

RESULTS: 48 studies (3372 participants, mean age 42 years, and with a mean testing time of 4 months post-COVID-19) were included, comprising a total of 1823 COVID-19 survivors and 1549 non-COVID-19 controls. After data pooling, VO2 peak (SMD=1.0 95% CI: 0.5, 1.5; 17 studies; N = 1273) was impaired in COVID-19 survivors. In 15 studies that reported VO2 peak values in mL/min/kg, non-COVID-19 controls had higher peak VO2 values than COVID-19 survivors (MD=6.2, 95% CI: 3.5, 8.8; N = 905; I[2]=84%). In addition, VO2 peak was associated with age, time post-COVID-19, disease severity, presence of dyspnea, and reduced exercise capacity.

CONCLUSION: This systematic review provides evidence that cardiorespiratory fitness may be impaired in COVID-19 survivors, especially for those with severe disease, presence of dyspnea, and reduced exercise capacity. Furthermore, the degree of reduction of VO2 peak is inversely associated with age and time post-COVID.}, } @article {pmid38934345, year = {2024}, author = {Kondo, T and Higa, R and Kuniba, M and Shinzato, H and Takaesu, Y}, title = {Successful treatment with guanfacine in a long-COVID case manifesting marked cognitive impairment.}, journal = {Neuropsychopharmacology reports}, volume = {44}, number = {3}, pages = {585-590}, pmid = {38934345}, issn = {2574-173X}, mesh = {Humans ; Female ; Adult ; *Cognitive Dysfunction/drug therapy/etiology ; *Guanfacine/therapeutic use/administration & dosage ; *COVID-19/complications ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Adrenergic alpha-2 Receptor Agonists/administration & dosage/therapeutic use ; Neuropsychological Tests ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Persistent cognitive impairment is a serious consequence of the post-COVID condition. However, there have been no established effective treatments for this pathophysiology supported by sufficient evidence.

CASE PRESENTATION: A 32-year-old woman became aware of difficulty in word recalling, reading, and writing as well as difficulty in completing various household multitasks 3 weeks after the COVID-19 infection. Although blood tests, magnetic resonance imaging, electroencephalography, and Kohs block design test were all within normal limits, completion time by trail making test (TMT) A or B was markedly delayed. Finally, she was referred to our hospital 3 months after the infection. At baseline, the THINC integrated tool (THINC-it), a digital battery consisting of the five-item version of the perceived deficit questionnaire (PDQ-5), choice reaction time (CRT), 1-back test, digit symbol substitution test (DSST), and TMT-B, revealed poor capability in attention, working memory, and executive function. Also, near-infrared spectroscopy (NIRS) demonstrated no activation in frontal or temporal regions during verbal fluency task. Extended-release guanfacine (GXR) 2 mg/day was initiated and a month later was elevated up to 4 mg/day as a maintenance dose. The PDQ-5, CRT, 1-back test, DSST, and TMT-B were dramatically improved 1 month after GXR treatment. NIRS finding was also normalized after 2 months of treatment. These effects were successfully maintained throughout the 6-month follow-up period.

CONCLUSION: GXR may be helpful in improving subjective/objective cognitive functioning and frontotemporal brain activity in long-COVID patients manifesting apparent cognitive impairment.}, } @article {pmid38932420, year = {2024}, author = {Claus, J and Ten Doesschate, T and Taks, E and Debisarun, PA and Smits, G and van Binnendijk, R and van der Klis, F and Verhagen, LM and de Jonge, MI and Bonten, MJM and Netea, MG and van de Wijgert, JHHM}, title = {Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.}, journal = {Vaccines}, volume = {12}, number = {6}, pages = {}, pmid = {38932420}, issn = {2076-393X}, support = {10430 01 201 0026//Netherlands Organisation for Health Research and Development/ ; }, abstract = {SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.}, } @article {pmid38932418, year = {2024}, author = {Romeiser, JL and Schoeneck, K}, title = {COVID-19 Booster Vaccination Status and Long COVID in the United States: A Nationally Representative Cross-Sectional Study.}, journal = {Vaccines}, volume = {12}, number = {6}, pages = {}, pmid = {38932418}, issn = {2076-393X}, abstract = {Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 US National Health Interview Survey data to investigate how vaccination status correlates with COVID-19 infection severity and long COVID among previously infected individuals. Participants were categorized into three groups: those who had received at least one booster, those with only the initial complete vaccination series, and those with either an incomplete series or no vaccinations. Out of 9521 survey respondents who reported a past positive COVID-19 test, 51.2% experienced moderate/severe infections, and 17.6% experienced long COVID. Multivariable regression models revealed that receiving at least one booster shot was associated with lower odds of experiencing moderate/severe symptoms (aOR = 0.78, p < 0.001) compared to those unvaccinated or with an incomplete series. Additionally, having at least one booster reduced long COVID odds by 24% (aOR = 0.76, p = 0.003). Completing only the primary vaccine series did not significantly decrease the likelihood of severe illness or long COVID. These findings support the continued promotion of booster vaccinations to mitigate long COVID risks in vulnerable populations.}, } @article {pmid38932408, year = {2024}, author = {Martín-Martín, C and Del Riego, ES and Castiñeira, JRV and Zapico-Gonzalez, MS and Rodríguez-Pérez, M and Corte-Iglesias, V and Saiz, ML and Diaz-Bulnes, P and Escudero, D and Suárez-Alvarez, B and López-Larrea, C}, title = {Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8[+] T-Cell Response in Patients with Severe Symptoms.}, journal = {Vaccines}, volume = {12}, number = {6}, pages = {}, pmid = {38932408}, issn = {2076-393X}, support = {PI19/00184, PI20/00639 and PI22/00738//Instituto de Salud Carlos III (ISCIII) through projects co-funded by the European Union/ ; IFEQ21/00203//European Union through Next Generation EU funds, which support the actions of the Mecanismo de Recuperación y Resiliencia (MRR)./ ; Grant IDI/2021/000032//PCTI-Plan de Ciencia, Tecnología e Innovación 2021-2023 from the Gobierno del Principado de Asturias/ ; }, abstract = {Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8[+] T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8[+] T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8[+] T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8[+] T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.}, } @article {pmid38932398, year = {2024}, author = {Nguyen, KH and Bao, Y and Chen, S and Bednarczyk, RA and Vasudevan, L and Corlin, L}, title = {Prior COVID-19 Diagnosis, Severe Outcomes, and Long COVID among U.S. Adults, 2022.}, journal = {Vaccines}, volume = {12}, number = {6}, pages = {}, pmid = {38932398}, issn = {2076-393X}, support = {R37 CA234119/CA/NCI NIH HHS/United States ; }, abstract = {Given the increase in COVID-19 emergency department visits and hospitalizations during the winter of 2023-2024, identifying groups that have a high prevalence of COVID-19 cases, severity, and long-term symptoms can help increase efforts toward reducing disparities and prevent severe COVID-19 outcomes. Using data from the 2022 National Health Interview Survey (n = 27,651), we assessed the prevalence of COVID-19 outcomes (prior diagnosis, moderate/severe COVID-19, and long COVID) by sociodemographic characteristics and factors associated with each COVID-19 outcome. Approximately one third of adults reported a prior COVID-19 diagnosis (30.7%), while one half (51.6%) who had COVID-19 reported moderate or severe symptoms, and one fifth (19.7%) who had COVID-19 symptoms reported long COVID. The following were associated with higher odds of moderate/severe COVID-19 and long COVID: havinga high-risk condition (aOR = 1.20, OR = 1.52); having anxiety or depression (OR = 1.46, OR = 1.49); having a disability (OR = 1.41, OR = 1.60); and having a food insecurity (OR = 1.37, OR = 1.50) compared to a lack of these conditions. Having two or more COVID-19 vaccinations was associated with lower odds of a COVID-19 diagnosis (OR = 0.75), moderate/severe COVID-19 (OR = 0.86), and long COVID (OR = 0.82). Improving vaccination coverage and reducing disparities in COVID-19 outcomes could advance health equities and protect against future resurgence of disease.}, } @article {pmid38932339, year = {2024}, author = {Hamzaraj, K and Han, E and Hasimbegovic, E and Poschenreiter, L and Vavrikova, A and Lukovic, D and Kastrati, L and Bergler-Klein, J and Gyöngyösi, M}, title = {Impact of Circulating Anti-Spike Protein Antibody Levels on Multi-Organ Long COVID Symptoms.}, journal = {Vaccines}, volume = {12}, number = {6}, pages = {}, pmid = {38932339}, issn = {2076-393X}, support = {KLI 1064-B//FWF Austrian Science Fund/ ; 21176//Medical Scientific Fund of the Mayor of the City of Vienna/ ; }, abstract = {Patients with long COVID syndrome present with various symptoms affecting multiple organs. Vaccination before or after SARS-CoV-2 infection appears to reduce the incidence of long COVID or at least limit symptom deterioration. However, the impact of vaccination on the severity and extent of multi-organ long COVID symptoms and the relationship between the circulating anti-spike protein antibody levels and the severity and extent of multi-organ symptoms are unclear. This prospective cohort study included 198 patients with previous PCR-verified SARS-CoV-2 infection who met the criteria for long COVID syndrome. Patients were divided into vaccinated (n = 138, 69.7%) or unvaccinated (n = 60, 30.3%) groups. Anti-spike protein antibody levels were determined at initial clinical presentation and compared between the groups. Long COVID symptoms were quantified on the basis of the number of affected organs: Class I (mild) with symptoms in three organs, Class II (moderate) with symptoms in four to five organs, and Class III (severe) with symptoms in six or more organ systems. Associations between time to infection and vaccination with anti-spike protein antibody levels were assessed. The anti-spike protein antibody levels were 1925 ± 938 vs. 481 ± 768 BAU/mL (p < 0.001) in the vaccinated vs. unvaccinated patients. The circulating anti-spike antibody cutoff of 665.5 BAU/mL allowed us to differentiate the vaccinated from the unvaccinated patients. Vaccinated patients had fewer class II and class III multi-organ symptoms (Class II 39.9% vs. 45.0%; Class III 10.1% vs. 23.3%, p-value 0.014). Anti-spike antibody level correlated negatively with multi-organ symptom classes (p = 0.016; 95% CI -1.229 to -0.126). Anti-spike antibody levels in unvaccinated patients declined markedly with time, in contrast to the persistence of high anti-spike antibody levels in the vaccinated patients. Multi-organ symptoms were lower in vaccinated long-COVID patients, especially in those with higher anti-spike antibody levels (≥665.5 BAU/mL). Classifying the symptoms on the basis of the number of affected organs enables a more objective symptom quantification.}, } @article {pmid38932239, year = {2024}, author = {Fernández-de-Las-Peñas, C and Franco-Moreno, A and Ruiz-Ruigómez, M and Arrieta-Ortubay, E and Ryan-Murua, P and Lumbreras-Bermejo, C and Del-Valle-Loarte, P and Pellicer-Valero, OJ and Giordano, R and Arendt-Nielsen, L and Martín-Garrido, I and Torres-Macho, J}, title = {Is Antiviral Treatment with Remdesivir at the Acute Phase of SARS-CoV-2 Infection Effective for Decreasing the Risk of Long-Lasting Post-COVID Symptoms?.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932239}, issn = {1999-4915}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, mesh = {Humans ; *Alanine/analogs & derivatives/therapeutic use/administration & dosage ; *Adenosine Monophosphate/analogs & derivatives/therapeutic use/administration & dosage ; Female ; Male ; *Antiviral Agents/therapeutic use ; *COVID-19 Drug Treatment ; Middle Aged ; *SARS-CoV-2/drug effects ; *COVID-19/complications ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Adult ; Aged ; }, abstract = {The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256-0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270-0.590), pain (OR0.368, 95% CI 0.248-0.548), dyspnea at rest (OR0.580, 95%CI 0.361-0.933), concentration loss (OR0.368, 95%CI 0.151-0.901), memory loss (OR0.399, 95%CI 0.270-0.590), hair loss (OR0.103, 95%CI 0.052-0.207), and skin rashes (OR0.037, 95%CI 0.005-0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors.}, } @article {pmid38932130, year = {2024}, author = {Elumalai, N and Hussain, H and Sampath, N and Shamaladevi, N and Hajjar, R and Druyan, BZ and Rashed, AB and Ramamoorthy, R and Kenyon, NS and Jayakumar, AR and Paidas, MJ}, title = {SPIKENET: An Evidence-Based Therapy for Long COVID.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932130}, issn = {1999-4915}, support = {0000//University of Miami Miller School of Medicine Department Obstetrics, Gynecology and Repro-ductive Sciences/ ; 0000//Muriel, Murray & Robert Smith Foundation COVID-19 Research Fund/ ; 0000//University of Miami Miller School of Medicine Team Science Award/ ; 0000//Charles M. Vallee Foundation/ ; }, mesh = {*SARS-CoV-2/drug effects ; Humans ; *COVID-19/therapy/virology ; Animals ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; Mice ; Post-Acute COVID-19 Syndrome ; Angiotensin-Converting Enzyme 2/metabolism ; Peptides/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19 Drug Treatment ; }, abstract = {The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.}, } @article {pmid38932125, year = {2024}, author = {Hussain, H and Elumalai, N and Sampath, N and Shamaladevi, N and Hajjar, R and Druyan, BZ and Rashed, AB and Ramamoorthy, R and Kenyon, NS and Jayakumar, AR and Paidas, MJ}, title = {Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932125}, issn = {1999-4915}, mesh = {Animals ; Mice ; *COVID-19/pathology/virology/immunology ; *Disease Models, Animal ; *Murine hepatitis virus/pathogenicity ; *SARS-CoV-2/pathogenicity ; Intestinal Mucosa/pathology/virology ; Intestines/pathology/virology ; Intestine, Small/virology/pathology ; Female ; }, abstract = {The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.}, } @article {pmid38931912, year = {2024}, author = {Frank, N and Dickinson, D and Lovett, G and Liu, Y and Yu, H and Cai, J and Yao, B and Jiang, X and Hsu, S}, title = {Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment.}, journal = {Pharmaceutics}, volume = {16}, number = {6}, pages = {}, pmid = {38931912}, issn = {1999-4923}, support = {1R41DC020678-01/GF/NIH HHS/United States ; }, abstract = {UNLABELLED: Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to these symptoms, leading to a USD 50 billion annual loss of salary. Neurological symptoms associated with long COVID result from persistent infection with SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous system (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in olfactory mucosa. Recently published clinical data demonstrate that only 5% of long COVID anosmia patients have fully recovered during the past 2 years, and 10.4% of COVID patients are still symptomatic 18 months post-infection. Our group demonstrated that epigallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activity against human coronavirus, suggesting that this green-tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to restoration of neurologic functions. The objective of the current study was to evaluate the mucociliary safety of the EC16m nasal nanoformulations and their efficacy against human coronavirus.

METHODS: Nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using the MucilAir human nasal model; contact antiviral activity and post-infection inhibition against the OC43 viral strain were assessed by the TCID50 assay for cytopathic effect on MRC-5 cells.

RESULTS: The saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference compared to saline (0.9% NaCl) with respect to tissue integrity, cytotoxicity, and cilia beat frequency. A 5 min contact resulted in 99.9% inactivation of β-coronavirus OC43. OC43 viral replication was inhibited by >90% after infected MRC-5 cells were treated with the formulations.

CONCLUSION: The saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety properties comparable to saline, a solution widely used for nasal applications.}, } @article {pmid38930148, year = {2024}, author = {Nantakool, S and Sa-Nguanmoo, P and Konghakote, S and Chuatrakoon, B}, title = {Effects of Exercise Rehabilitation on Cardiorespiratory Fitness in Long-COVID-19 Survivors: A Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {12}, pages = {}, pmid = {38930148}, issn = {2077-0383}, abstract = {Background: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise rehabilitation, such as cardiopulmonary exercise, is used for long-COVID-19 survivors, the effects of exercise on CRF in this population remain inconclusive. In this study, we aim to systematically summarise and synthesise whether exercise rehabilitation improves CRF among long-COVID-19 survivors. Methods: A comprehensive search was performed through PubMed, CINAHL, Embase, Scopus, and the Cochrane Library (since their inception to November 2023) and study reference lists. Studies presenting the effects of exercise rehabilitation on CRF (peak oxygen consumption (VO2peak) and six-minute walk distance (6MWD)) in long-COVID-19 survivors were identified. The standardised mean difference (SMD), mean difference (MD), and 95% confidence interval (CI) were used for analyses. The certainty of evidence was measured using a Grading of Recommendation Assessment, Development and Evaluation approach. Results: Twelve eligible studies (five RCTs and seven non-RCTs) with 682 participants were analysed. The meta-analysis showed significantly improved 6MWDs (MD 76.47, 95% CI 59.19-93.71, low certainty) and significantly greater 6MWDs (SMD 0.85, 95% CI 0.11-1.59, very low certainty) in the exercise rehabilitation group compared to the control group. A significantly improved 6MWD was found in subgroups of young to middle-aged adults and subgroups of patients who undertook aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. Conclusions: Exercise rehabilitation is effective for improving CRF, as measured by the 6MWD in long-COVID-19 survivors. Improvements are likely to be more pronounced in specific subgroups of young to middle-aged adults and patients undertaking aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. However, recommendations for clinical practice are limited due to the very low evidence certainty.}, } @article {pmid38929912, year = {2024}, author = {Zalewska, A and Gałczyk, M}, title = {Fatigue, Internet Addiction and Symptoms of Long COVID-A Cross-Sectional Study of Polish Students.}, journal = {Journal of clinical medicine}, volume = {13}, number = {12}, pages = {}, pmid = {38929912}, issn = {2077-0383}, abstract = {Introduction: Fatigue is the most persistent symptom in patients with long COVID. Moreover, Internet addiction itself has become a pandemic long-term effect. The aim of this study was to investigate the degree of fatigue and Internet addiction in a group of students with COVID-19 and to determine the relationship between fatigue and addiction in students with and without long COVID symptoms. Material and methods: A cross-sectional study was conducted among 402 Polish students aged 19-26. The 183 students who had COVID-19 signaled the presence of long COVID symptoms, which corresponded to 45.5% of the surveyed group. The Modified Fatigue Impact Scale was used to assess the level of fatigue, and the Kimberly Young questionnaire was used to assess the level of Internet addiction. Results: 19.7% (95% c.i.: 15.9-23.9%) of the students surveyed had a moderate level of Internet dependence (Internet addiction measure value of 50 points or more). Most of them did not complain of high levels of fatigue. Higher levels of dependence and fatigue were observed in subjects with long COVID symptoms (MFIS mean value was 26.5 in this group vs. 17.7 in the others; p = 0.0000 ***). The higher the respondents' level of dependence, the more they tended to feel tired (correlations were stronger in those with long COVID symptoms: rS = 0.23; p = 0.0017 **). Conclusions: In view of the results obtained, the study presented here has the potential to contribute to the international debate on the long-term health consequences of the COVID-19 pandemic and strategies to address them. The study provides data that may be useful in the development of educational and health policies that target the psychophysical well-being of patients with long COVID symptoms. This process should be considered as a long-term endeavor.}, } @article {pmid38929823, year = {2024}, author = {Leone, V and Freuer, D and Goßlau, Y and Kirchberger, I and Warm, T and Hyhlik-Dürr, A and Meisinger, C and Linseisen, J}, title = {Symptom Clusters in Acute SARS-CoV-2 Infection and Long COVID Fatigue in Male and Female Outpatients.}, journal = {Journal of personalized medicine}, volume = {14}, number = {6}, pages = {}, pmid = {38929823}, issn = {2075-4426}, support = {NA//Bavarian state funding for SARS-CoV-2 research projects 2020/ ; }, abstract = {(1) Background: After an acute SARS-CoV-2 infection, patients are at risk of developing Long COVID, with fatigue as a frequent and serious health problem. Objectives: To identify symptom clusters in acute SARS-CoV-2 infections and investigate their associations with the development of Long COVID fatigue, and to examine sex-specific differences. (2) Methods: The analysis included a total of 450 COVID-19 outpatients, of whom 54.4% were female. The median ages of the men and women were 51 years (IQR 36.0; 60.0) and 48 years (IQR 33.0; 57.0), respectively. Data collection took place between November 2020 and May 2021, with a median time between acute SARS-CoV-2 infection and examination in the study center of 240 days (IQR 133; 326). The Fatigue Assessment Scale (FAS) was used to identify fatigue and its severity. A multiple correspondence analysis was used to group forty-two COVID-19 symptoms into seven symptom clusters. Logistic and log-linear regressions were used to investigate associations between acute symptom clusters and Long COVID fatigue as dichotomous and continuous outcome, respectively. (3) Results: Fatigue occurred more frequently in women than in men (45% vs. 25%) and the median FAS score, indicating severity of fatigue, was higher in women than in men. The comparison between men and women revealed notable differences in four out of seven clusters. The strongest associations between symptom clusters in infection and Long COVID fatigue were identified for the cluster "cognitive and mental symptoms". In the log-linear regression model, each additional symptom in this cluster was associated with an increase of the FAS score by 5.13% (95% CI: [0.04; 0.07]; p < 0.001). The results of the logistic regression models supported this finding. Each additional symptom in this symptom cluster increased the odds of fatigue by 42% (95% CI: [1.23; 1.66]; p < 0.001). (4) Conclusions: In our study in COVID-19 outpatients, a strong association was observed between the number of symptoms in the cluster "cognitive and mental symptoms" during acute SARS-CoV-2 infection and the risk of developing fatigue months later. The consequent use of preventive and therapeutic strategies is necessary to decrease the burden of fatigue in the context of Long COVID.}, } @article {pmid38929561, year = {2024}, author = {Gutiérrez-Canales, LG and Muñoz-Corona, C and Barrera-Chávez, I and Viloria-Álvarez, C and Macías, AE and Martínez-Navarro, LJ and Alvarez, JA and Scavo-Montes, DA and Guaní-Guerra, E}, title = {Persistence of COVID-19 Symptoms and Quality of Life at Three and Twelve Months after Hospital Discharge.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {6}, pages = {}, pmid = {38929561}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/psychology ; *Quality of Life ; Female ; Male ; Middle Aged ; Prospective Studies ; *Patient Discharge ; Longitudinal Studies ; Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; Myalgia ; Time Factors ; Cough/psychology ; Alopecia/psychology ; }, abstract = {Background and Objectives: Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease burden. Objectives: We aimed to describe the persistence of COVID-19 symptoms and QoL among patients at three and twelve months after their discharge from the hospital. Materials and Methods: We conducted an observational, prospective, and longitudinal analytic study from September 2021 to April 2022. To measure QoL, we used a validated version of the 36-item Short-Form Health Survey (SF-36). Results: We included 68 patients in the study. A total of 54 (79.4%) patients reported at least one persistent symptom at three months vs. 52 (76.4%) at twelve months (p = 0.804). Some persistent symptoms (myalgia, alopecia, and cough) decreased significantly at twelve months (50% vs. 30.9%, 29.4% vs. 13.2%, and 23.5% vs. 7.4%; respectively, p = 0.007); in contrast, other persistent symptoms (sleep-wake and memory disorders) were more frequent (5.9% vs. 32.4% and 4.4% vs. 20.6%; respectively, p = ≤0.001). Regarding QoL, a statistically significant improvement was observed in some scores over time, p = ≤0.037. At twelve months, dyspnea, myalgia, and depression were risk factors associated with a poor physical component summary (PCS), p = ≤0.027, whereas anxiety, depression, and fatigue were associated with a poor mental component summary (MCS), p = ≤0.015. Conclusion: As the proportion of persistent symptoms at twelve months is high, we suggest that patients must continue under long-term follow up to reclassify, diagnose, and treat new onset symptoms/diseases.}, } @article {pmid38928701, year = {2024}, author = {Berger, L and Wolf, J and Kalbitz, S and Kellner, N and Lübbert, C and Borte, S}, title = {Comparative Analysis of Lymphocyte Populations in Post-COVID-19 Condition and COVID-19 Convalescent Individuals.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, pmid = {38928701}, issn = {2075-4418}, support = {program of Open Access Publishing//University of Leipzig/ ; JMF Leipzig//Jeffrey Modell Foundation for Primary Immunodeficiencies/ ; }, abstract = {Reduced lymphocyte counts in peripheral blood are one of the most common observations in acute phases of viral infections. Although many studies have already examined the impact of immune (dys)regulation during SARS-CoV-2 infection, there are still uncertainties about the long-term consequences for lymphocyte homeostasis. Furthermore, as persistent cellular aberrations have been described following other viral infections, patients with "Post-COVID-19 Condition" (PCC) may present similarly. In order to investigate cellular changes in the adaptive immune system, we performed a retrospective analysis of flow cytometric data from lymphocyte subpopulations in 106 patients with confirmed SARS-CoV-2 infection who received medical care at our institution. The patients were divided into three groups according to the follow-up date; laboratory analyses of COVID-19 patients were compared with 28 unexposed healthy controls. Regarding B lymphocyte subsets, levels of IgA + CD27+, IgG + CD27+, IgM + CD27- and switched B cells were significantly reduced at the last follow-up compared to unexposed healthy controls (UHC). Of the 106 COVID-19 patients, 56 were clinically classified as featuring PCC. Significant differences between PCC and COVID-19 convalescents compared to UHC were observed in T helper cells and class-switched B cells. However, we did not detect specific or long-lasting immune cellular changes in PCC compared to the non-post-COVID-19 condition.}, } @article {pmid38928604, year = {2024}, author = {Almeria, M and Cejudo, JC and Deus, J and Krupinski, J}, title = {Neurocognitive and Neuropsychiatric Sequelae in Long COVID-19 Infection.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928604}, issn = {2076-3425}, abstract = {Objective: To characterize the cognitive profile of long COVID-19 subjects and its possible association with clinical symptoms, emotional disturbance, biomarkers, and disease severity. Methods: We performed a single-center cross-sectional cohort study. Subjects between 20 and 60 years old with confirmed COVID-19 infection were included. The assessment was performed 6 months following hospital or ambulatory discharge. Excluded were those with prior neurocognitive impairment and severe neurological/neuropsychiatric disorders. Demographic and laboratory data were extracted from medical records. Results: Altogether, 108 participants were included, 64 were male (59.25%), and the mean age was 49.10 years. The patients were classified into four groups: non-hospitalized (NH, n = 10), hospitalized without Intensive Care Unit (ICU) or oxygen therapy (HOSPI, n = 21), hospitalized without ICU but with oxygen therapy (OXY, n = 56), and ICU (ICU, n = 21) patients. In total, 38 (35.18%) reported Subjective Cognitive Complaints (SCC). No differences were found considering illness severity between groups. Females had more persistent clinical symptoms and SCC than males. Persistent dyspnea and headache were associated with higher scores in anxiety and depression. Persistent fatigue, anxiety, and depression were associated with worse overall cognition. Conclusions: No cognitive impairment was found regarding the severity of post-COVID-19 infection. SCC was not associated with a worse cognitive performance, but with higher anxiety and depression. Persistent clinical symptoms were frequent independent of illness severity. Fatigue, anxiety, and depression were linked to poorer cognitive function. Tests for attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients.}, } @article {pmid38928587, year = {2024}, author = {Rudroff, T}, title = {Long COVID in Brain Health Research: A Call to Action.}, journal = {Brain sciences}, volume = {14}, number = {6}, pages = {}, pmid = {38928587}, issn = {2076-3425}, abstract = {The COVID-19 pandemic has brought attention to the long-term consequences of the virus, particularly the persistent symptoms that characterize long COVID. This syndrome, which can last for months after the initial infection, includes a range of neurological and neuropsychiatric manifestations that have significant implications for brain health and dementia research. This review explores the current understanding of long COVID's cognitive, neurological, and psychiatric symptoms and their potential impact on brain stimulation and neuroimaging studies. It argues that researchers must adapt their study designs and screening processes to account for the confounding effects of long COVID and ensure the accuracy and reliability of their findings. To advance the understanding of this condition and its long-term effects on brain health, the review proposes a series of strategies, including the development of standardized screening tools, the investigation of underlying mechanisms, and the identification of risk factors and protective factors. It also emphasizes the importance of collaborative research efforts and international data sharing platforms in accelerating the pace of discovery and developing targeted interventions for individuals with long COVID. As the prevalence of this condition continues to grow, it is imperative that the neuroscience community comes together to address this challenge and support those affected by long COVID.}, } @article {pmid38928096, year = {2024}, author = {Gusev, E and Sarapultsev, A}, title = {Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement.}, journal = {International journal of molecular sciences}, volume = {25}, number = {12}, pages = {}, pmid = {38928096}, issn = {1422-0067}, support = {122020900136-4//Institute of Immunology and Physiology/ ; }, mesh = {Humans ; *COVID-19/physiopathology/complications/virology/pathology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Inflammation ; }, abstract = {Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.}, } @article {pmid38927489, year = {2024}, author = {Pietruszka-Wałęka, E and Rząd, M and Rożyńska, R and Miklusz, P and Zieniuk-Lesiak, E and Żabicka, M and Jahnz-Różyk, K}, title = {Quality of Life in Follow-Up up to 9 Months after COVID-19 Hospitalization among the Polish Population-A Prospective Single Center Study.}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927489}, issn = {2227-9059}, abstract = {The consequences of COVID-19 constitute a significant burden to healthcare systems worldwide. Conducting an HRQoL assessment is an important aspect of the evaluation of the impact of the disease. The aim of this study was to investigate the prevalence of persistent symptoms and their impact on HRQoL and health status in COVID-19 convalescents. The study group consists of 46 patients who required hospitalization due to respiratory failure and who were subsequently evaluated 3 and 9 months after hospital discharge. At the follow-up visits, the patients were asked to assess their HRQoL using the EQ-5D-5L questionnaire. The results of chest CT, 6MWT, as well as the severity of the course of COVID-19 were also considered in the analysis. The obtained results have identified fatigue as the most common persistent symptom. The majority of the convalescents reported an impairment of HRQoL in at least one domain (80% and 82% after 3 and 9 months, respectively), of which the most common was that of pain/discomfort. The presence of ongoing symptoms may affect HRQoL in particular domains. The 6MWT outcome correlates with HRQoL 3 months after hospital discharge. Therefore, it may be useful in identifying patients with reduced HRQoL, allowing early interventions aimed at its improvement.}, } @article {pmid38927466, year = {2024}, author = {Filev, R and Lyubomirova, M and Bogov, B and Kalinov, K and Hristova, J and Svinarov, D and Garev, A and Rostaing, L}, title = {Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) for Patients-3-Year Follow-Up of Patients with Chronic Kidney Disease.}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927466}, issn = {2227-9059}, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. Data were collected from both CKD and non-CKD patients who survived SARS-CoV-2 infection and were followed for three years as part of a research study on the impact, prognosis, and consequences of COVID-19 infection in CKD patients. In this prospective cohort study, we analyzed clinical records, laboratory findings, and patient-reported outcomes assessed at intervals during follow-up. The results indicated no permanent changes in renal function in any of the groups analyzed, although patients without CKD exhibited faster recovery over time. Furthermore, we examined the effect of RAAS-blocker therapy over time, finding no influence on PASC symptoms or renal function recovery. Regarding PASC symptoms, most patients recovered within a short period, but some required prolonged follow-up and specialized post-recovery management. Following up with patients in the post-COVID-19 period is crucial, as there is still insufficient information and evidence regarding the long-term effects, particularly in relation to CKD.}, } @article {pmid38927441, year = {2024}, author = {Bazdar, S and Bloemsma, LD and Baalbaki, N and Blankestijn, JM and Cornelissen, MEB and Beijers, RJHCG and Sondermeijer, BM and van Wijck, Y and Downward, GS and Maitland-van der Zee, AH and , }, title = {Hemoglobin and Its Relationship with Fatigue in Long-COVID Patients Three to Six Months after SARS-CoV-2 Infection.}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927441}, issn = {2227-9059}, support = {LSHM20104; LSHM20068//Health Holland/ ; }, abstract = {Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the association between hemoglobin and fatigue in a cohort of Long-COVID patients. Methods: This prospective cohort study in the Netherlands evaluated 95 (mostly hospitalized) patients, aged 40-65 years, 3-6 months post SARS-CoV-2 infection, examining their venous hemoglobin concentration, anemia (hemoglobin < 7.5 mmol/L in women and <8.5 mmol/L in men), inflammatory blood biomarkers, average FSS (Fatigue Severity Score), demographics, and clinical features. Follow-up hemoglobin was compared against hemoglobin during acute infection. Spearman correlation was used for assessing the relationship between hemoglobin concentrations and inflammatory biomarkers, and the association between hemoglobin and fatigue was examined using logistic regression. Results: In total, 11 (16.4%) participants were suffering from anemia 3-6 months after SARS-CoV-2 infection. The mean hemoglobin value increased by 0.3 mmol/L 3-6 months after infection compared to the hemoglobin during the acute phase (p-value = 0.003). Whilst logistic regression showed that a 1 mmol/L greater increase in hemoglobin is related to a decrease in experiencing fatigue in Long-COVID patients (adjusted OR 0.38 [95%CI 0.13-1.09]), we observed no correlations between hemoglobin and any of the inflammatory biomarkers examined. Conclusion: Our results indicate that hemoglobin impairment might play a role in developing Long-COVID fatigue. Further investigation is necessary to identify the precise mechanism causing hemoglobin alteration in these patients.}, } @article {pmid38927430, year = {2024}, author = {Chang, MH and Park, JH and Lee, HK and Choi, JY and Koh, YH}, title = {SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of Metformin.}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927430}, issn = {2227-9059}, support = {2021-NI-020-02//Research of Korea Centers for Disease Control and Prevention/ ; 2020-NI-024-02//Research of Korea Centers for Disease Control and Prevention/ ; }, abstract = {Abnormal aggregation of α-synuclein is the hallmark of neurodegenerative diseases, classified as α-synucleinopathies, primarily occurring sporadically. Their onset is associated with an interaction between genetic susceptibility and environmental factors such as neurotoxins, oxidative stress, inflammation, and viral infections. Recently, evidence has suggested an association between neurological complications in long COVID (sometimes referred to as 'post-acute sequelae of COVID-19') and α-synucleinopathies, but its underlying mechanisms are not completely understood. In this study, we first showed that SARS-CoV-2 Spike protein 1 (S1) induces α-synuclein aggregation associated with activation of microglial cells in the rodent model. In vitro, we demonstrated that S1 increases aggregation of α-synuclein in BE(2)M-17 dopaminergic neurons via BV-2 microglia-mediated inflammatory responses. We also identified that S1 directly affects aggregation of α-synuclein in dopaminergic neurons through increasing mitochondrial ROS, though only under conditions of sufficient α-Syn accumulation. In addition, we observed a synergistic effect between S1 and the neurotoxin MPP+ S1 treatment. Combined with a low dose of MPP+, it boosted α-synuclein aggregation and mitochondrial ROS production compared to S1 or the MPP+ treatment group. Furthermore, we evaluated the therapeutic effects of metformin. The treatment of metformin suppressed the S1-induced inflammatory response and α-synucleinopathy. Our findings demonstrate that S1 promotes α-synucleinopathy via both microglia-mediated inflammation and mitochondrial ROS, and they provide pathological insights, as well as a foundation for the clinical management of α-synucleinopathies and the onset of neurological symptoms after the COVID-19 outbreak.}, } @article {pmid38927395, year = {2024}, author = {Fernández-de-Las-Peñas, C}, title = {Special Issue "Latest Research in Post-COVID (Long COVID): Pathological and Treatment Studies of Sequelae and Complications".}, journal = {Biomedicines}, volume = {12}, number = {6}, pages = {}, pmid = {38927395}, issn = {2227-9059}, abstract = {The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen provoked the most unprecedented sanitary outbreak of the current century by causing coronavirus disease 2019 (COVID-19), which has led to approximately 775 million confirmed cases and more than 7 million deaths globally [...].}, } @article {pmid38927239, year = {2024}, author = {D'Anna, SE and Vitale, AM and D'Amico, G and Caruso Bavisotto, C and Ambrosino, P and Cappello, F and Maniscalco, M and Marino Gammazza, A}, title = {Autoimmunity against Nucleus Ambiguous Is Putatively Possible in Both Long-COVID-19 and Vaccinated Subjects: Scientific Evidence and Working Hypothesis.}, journal = {Biology}, volume = {13}, number = {6}, pages = {}, pmid = {38927239}, issn = {2079-7737}, abstract = {As reported by the World Health Organization (WHO), about 10-20% of people have experienced mid- to long-term effects following SARS-CoV-2 infection, collectively referred to as post-COVID-19 condition or long-COVID, including some neurovegetative symptoms. Numerous findings have suggested that the onset of these neurovegetative symptoms upon viral infection may be caused by the production of autoantibodies through molecular mimicry phenomena. Accordingly, we had previously demonstrated that 22 of the human proteins sharing putatively immunogenic peptides with SARS-CoV-2 proteins are expressed in the dorsal motor nucleus and nucleus ambiguous. Therefore, if molecular mimicry occurs following severe forms of COVID-19, there could be transitory or permanent damage in some vagal structures, resulting in a lower vagal tone and all the related clinical signs. We investigated the presence of autoantibodies against two proteins of vagal nuclei sharing a peptide with SARS-CoV-2 spike glycoprotein using an immunoassay test on blood obtained from patients with cardiorespiratory symptoms in patients affected by ongoing symptomatic COVID-19 (long-COVID), subjects vaccinated without a history of SARS-CoV-2 infection, and subjects not vaccinated without a history of SARS-CoV-2 infection. Interestingly, putative autoantibodies were present in both long-COVID-19 and vaccinated groups, opening interesting questions about pathogenic mechanisms of the disease.}, } @article {pmid38924100, year = {2024}, author = {Ponce, J and Anzalone, AJ and Schissel, M and Bailey, K and Sayles, H and Timmerman, M and Jackson, M and Tefft, J and Hanson, C and , }, title = {Association between malnutrition and post-acute COVID-19 sequelae: A retrospective cohort study.}, journal = {JPEN. Journal of parenteral and enteral nutrition}, volume = {48}, number = {8}, pages = {906-916}, pmid = {38924100}, issn = {1941-2444}, support = {U54 GM115458/GM/NIGMS NIH HHS/United States ; U54GM115458//The project described was supported by the National Institute of General Medical Sciences/ ; R25AA020818//The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Other support for this project was provided by the NIAAA/ ; I01 CX001714/CX/CSRD VA/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; I01CX001714//The Department of Veterans Affairs/ ; U24 TR002306/TR/NCATS NIH HHS/United States ; R24 AA019661/AA/NIAAA NIH HHS/United States ; I01 BX006049/BX/BLRD VA/United States ; R25 AA020818/AA/NIAAA NIH HHS/United States ; U54GM104942//The project described was supported by the National Institute of General Medical Sciences/ ; R24AA019661//The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Other support for this project was provided by the NIAAA/ ; }, mesh = {Humans ; *COVID-19/complications/mortality/epidemiology ; *Malnutrition/epidemiology/complications ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Hospitalization ; Nutritional Status ; Risk Factors ; Cohort Studies ; Quality of Life ; }, abstract = {BACKGROUND: Long coronavirus disease consists of health problems people experience after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These can be severe and include respiratory, neurological, and gastrointestinal symptoms, with resulting detrimental impacts on quality of life. Although malnutrition has been shown to increase risk of severe disease and death during acute infection, less is known about its influence on post-acute COVID-19 outcomes. We addressed this critical gap in knowledge by evaluating malnutrition's impact on post-COVID-19 sequelae.

METHODS: This study leveraged the National COVID Cohort Collaborative to identify a cohort of patients who were at least 28 days post-acute COVID-19 infection. Multivariable Cox proportional hazard models evaluated the impact of malnutrition on the following postacute sequelae of SARS-CoV-2: (1) death, (2) long COVID diagnosis, (3) COVID-19 reinfection, and (4) other phenotypic abnormalities. A subgroup analysis evaluated these outcomes in a cohort of hospitalized patients with COVID-19 with hospital-acquired (HAC) malnutrition.

RESULTS: The final cohort included 4,372,722 individuals, 78,782 (1.8%) with a history of malnutrition. Individuals with malnutrition had a higher risk of death (adjusted hazard ratio [aHR]: 2.10; 95% CI: 2.04-2.17) and SARS-CoV-2 reinfection (aHR: 1.52; 95% CI: 1.43-1.61) in the postacute period than those without malnutrition. In the subgroup, those with HAC malnutrition had a higher risk of death and long COVID diagnosis.

CONCLUSION: Nutrition screening for individuals with acute SARS-CoV-2 infection may be a crucial step in mitigating life-altering, negative postacute outcomes through early identification and intervention of patients with malnutrition.}, } @article {pmid38924025, year = {2024}, author = {Reuschke, D and Houston, D and Sissons, P}, title = {Impacts of Long COVID on workers: A longitudinal study of employment exit, work hours and mental health in the UK.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0306122}, pmid = {38924025}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; United Kingdom/epidemiology ; *Mental Health ; Longitudinal Studies ; *Employment ; Male ; Female ; Adult ; Middle Aged ; SARS-CoV-2/isolation & purification ; Pandemics ; Adolescent ; Young Adult ; }, abstract = {BACKGROUND: The COVID-19 pandemic has had enormous implications for the world of work. However, there has been relatively little focus on the employment and workforce challenges of the virus in relation to workforce health, beyond the immediate management of the spread of the disease. There is an important gap in understanding the ongoing workforce issues created by the significant incidence of Long COVID in the population.

AIM: This paper examines the effects of Long COVID on employment and workers' mental health to contribute to understanding of work-limiting health conditions and to offer policy implications for COVID-19 and similar health conditions on employment and the workforce.

METHODS: A large national panel study for the UK is used to estimate the likelihood of exiting employment as well as on changes in working hours and general mental health and happiness of those who remain in work. The sample includes individuals 16 years and older who were in employment in January/February 2020 and followed during the pandemic 2020-2021. Long COVID is self-reported in the data. Informed by conceptual consideration of employment protection in the UK, two groups of individuals with Long COVID are defined based on the duration of symptoms. Group 1 has Long COVID 5-28 weeks after an infection with COVID-19, which is up to the maximum length of Statutory Sick Pay in the UK. Group 2 has symptoms for 29+ weeks, which is beyond the statutory entitlement to sickness pay. Panel regression models are fitted both with fixed-effects and random-effects. Individual and job characteristics are used as controls Those with no COVID-19 symptoms are the reference group.

RESULTS: In between-person comparison, Group 2 is at higher risk of exiting employment compared to those with no COVID-19 symptoms. Between-person estimates of mental health and well-being show negative effects of Long COVID for both groups but these are greatest in Group 2. Within-person estimates suggest that factors associated with earnings mediate the negative Long COVID effects on mental health in Group 1 and that Group 2 adapts to working with Long COVID. Group 1 is at risk of working zero hours (i.e. being on sick leave) but neither Group 1 nor Group 2 have a higher probability of working fewer hours compared to those with no COVID-19 symptoms. The negative impact of Long COVID on working hours stems primarily from working zero hours (sickness leave) rather than working fewer hours, suggesting a lack of accommodation by employers of Long COVID at work.

POLICY IMPLICATIONS: The extension of Statutory Sickness Pay and greater flexibility to manage partial (returns to) work would help preserve employment and mental health. Those with Long COVID for 12 months are likely to meet the definition of disability and so have a right to receive reasonable workplace adjustments.}, } @article {pmid38924005, year = {2024}, author = {Broughan, J and Sietiņš, E and Emily Siu, KY and Clendennen, N and Collins, C and Fawsitt, R and Lambert, JS and Savinelli, S and Skeffington, S and McCombe, G and Cullen, W}, title = {Enhancing long COVID care in general practice: A qualitative study.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0306077}, pmid = {38924005}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/therapy/psychology ; Female ; Male ; Middle Aged ; *General Practice ; Adult ; *General Practitioners/psychology ; *Qualitative Research ; Surveys and Questionnaires ; SARS-CoV-2 ; Physician-Patient Relations ; }, abstract = {INTRODUCTION: Research suggests that general practice can play an important role in managing long COVID. However, studies investigating the perspectives of general practitioners (GPs) and patients are lacking and knowledge regarding optimal long COVID care in general practice is therefore limited.

AIM: To investigate GPs' and patients' perspectives on the topic of long COVID and its management in general practice.

METHODS: Brief questionnaires (GP n = 11, Patient n = 7) and in-depth semi-structured interviews (GP n = 10, Patient n = 7) were conducted with GPs and patients from Irish general practices during July 2022-January 2023. Interviews were conducted via telephone and audio recordings were transcribed. A phenomenological analysis involving reflexive thematic analysis and constant comparison techniques was adopted.

RESULTS: Analysis of interviews with GPs (male = 7, female = 3; median age = 50yrs (IQR = 39.5-56)) and patients (males = 2, female = 5; median age = 58yrs (IQR = 45-62yrs) generated four themes. These were (1) Complex presentations (2) the value of standardising care, (3) choosing the right path, and (4) supportive and collaborative doctor-patient relationships. Strong agreement was observed among GPs and patients regarding the need for holistic and integrated multidisciplinary care. Supportive and collaborative doctor-patient relationships were largely well received by GPs and patients also. GPs strongly endorsed standardising long COVID care operations.

CONCLUSION: GPs and patients indicated that structured, integrated, and collaborative care can help optimise long COVID management in general practice. GPs are advised to incorporate these elements into their long COVID care practices going forward. Future research examining stakeholder's perspectives using larger and longitudinal samples is advised to enhance the generalisability of evidence in this area.}, } @article {pmid38923603, year = {2024}, author = {Gupta, A and Nicholas, R and McGing, JJ and Nixon, AV and Mallinson, JE and McKeever, TM and Bradley, CR and Piasecki, M and Cox, EF and Bonnington, J and Lord, JM and Brightling, CE and Evans, RA and Hall, IP and Francis, ST and Greenhaff, PL and Bolton, CE}, title = {DYNamic Assessment of Multi-Organ level dysfunction in patients recovering from COVID-19: DYNAMO COVID-19.}, journal = {Experimental physiology}, volume = {109}, number = {8}, pages = {1274-1291}, pmid = {38923603}, issn = {1469-445X}, mesh = {Humans ; *COVID-19/physiopathology ; Female ; Male ; Middle Aged ; *Insulin Resistance/physiology ; SARS-CoV-2 ; Blood Glucose/metabolism ; Fatigue/physiopathology ; Glucose Tolerance Test ; Adult ; Muscle Strength/physiology ; Aged ; Muscle, Skeletal/physiopathology/metabolism ; }, abstract = {We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.}, } @article {pmid38921807, year = {2024}, author = {Biondi, MJ and Addo, M and Zahoor, MA and Salvant, E and Yip, P and Barber, B and Smookler, D and Wasif, S and Gaete, K and Kandel, C and Feld, JJ and Tsui, H and Kozak, RA}, title = {Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, pmid = {38921807}, issn = {2076-0817}, support = {OV5-170347/CAPMC/CIHR/Canada ; }, abstract = {Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.}, } @article {pmid38920258, year = {2024}, author = {Mancini, D and Maffoni, M and Torlaschi, V and Gorini, A and La Rovere, MT and Fundarò, C and Fanfulla, F and Bussotti, M and Masnaghetti, S and Pierobon, A}, title = {Post-Acute Sequelae of COVID-19 Checklist (PASC-C): a screening tool for Long COVID physical, psychological, and cognitive symptoms.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {60}, number = {1}, pages = {47-54}, doi = {10.4415/ANN_24_01_07}, pmid = {38920258}, issn = {2384-8553}, mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; *Checklist ; Middle Aged ; Aged ; *Post-Acute COVID-19 Syndrome ; *Anxiety/etiology/psychology ; Fatigue/etiology/psychology ; Dyspnea/etiology/psychology ; Aged, 80 and over ; SARS-CoV-2 ; Adult ; }, abstract = {BACKGROUND: The management of Long COVID symptoms is necessary. This study proposes a screening tool for psycho-physical COVID-19 sequelae. Patients' experiences after COVID-19 are also described.

METHOD: 84 COVID-19 patients (66.2±11.0 years old; 71.4% male) underwent a phone interview 1-2 years after the disease using the ad-hoc "Post-Acute Sequelae of COVID-19 Checklist (PASC-C)". It explores 30 physical, psychological, and cognitive symptoms clustered into 10 areas, with possible clinical recommendations in case of high severity scores (>50) of a symptom or the presence of two or more ones within the same area.

RESULTS: Overall, fatigue (69%), dyspnea (52.4%), memory disturbances (44%), joint-muscle pain (41.7%), vision/hearing loss (40.5%), anxiety (40.5%) persist one-two years after COVID-19 disease. Being a survivor was primarily defined in terms of being "lucky".

CONCLUSIONS: PASC-C seems promising in monitoring psycho-physical sequelae of Long COVID and providing tailored suggestions to care for the patient over time.}, } @article {pmid38920203, year = {2023}, author = {Li, J and Nadua, K and Chong, CY and Yung, CF}, title = {Long COVID prevalence, risk factors and impact of vaccination in the paediatric population: A survey study in Singapore.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {52}, number = {10}, pages = {522-532}, doi = {10.47102/annals-acadmedsg.2023238}, pmid = {38920203}, issn = {2972-4066}, support = {PAEDSACPTCL/2022/RES/002//Tan Cheng Lim (TCL) Research and Education Grant/ ; }, mesh = {Humans ; Singapore/epidemiology ; *COVID-19/epidemiology/prevention & control ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Prevalence ; Infant ; Risk Factors ; SARS-CoV-2 ; Surveys and Questionnaires ; Vaccination/statistics & numerical data ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Infant, Newborn ; Case-Control Studies ; }, abstract = {INTRODUCTION: Information on the quality of health of children and younger persons (CYPs) after SARS-COV-2 infection remains scarce, especially from Asia. In this study, we utilised an online survey to investigate Long COVID prevalence in CYPs in Singapore.

METHOD: The study was an anonymised online survey of physical and functional symptoms, made available from 14 October 2022 to 15 January 2023. Caregivers of CYPs aged 0 to 18 years were invited to complete the survey on behalf of their CYPs. Participants provided demographic information and their history of SARS-CoV-2 infection status to allow classification into cases and controls for analysis.

RESULTS: A total of 640 completed responses were analysed, 471 (73.6%) were cases and 169 (26.4%) were controls. The prevalence of Long COVID ≥3 months post-infection was 16.8%. This decreased to 8.7% ≥6 months post-infection. Cases had higher odds of developing Long COVID (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.31-4.74). The most common symptoms of Long COVID were persistent cough (7.4%), nasal congestion (7.6%) and fatigue (3.0%). Male gender was significantly associated with higher odds of Long COVID (adjusted OR 1.71 [1.04-2.83]). Vaccinated CYPs had lower odds of Long COVID but this was not statically significant (adjusted OR 0.65, 95% CI 0.34-1.25).

CONCLUSION: About 1 in 6 CYPs in Singapore developed Long COVID with persistence of 1 or more symptoms ≥3 months post-infection, and approximately half will recover by 6 months. Male gender was associated with higher odds of Long COVID, and vaccination could potentially be protective against Long COVID in CYPs.}, } @article {pmid38919940, year = {2024}, author = {Delfino, C and Poli, MC and Vial, C and Vial, PA and Martínez, G and Riviotta, A and Arbat, C and Mac-Guire, N and Hoppe, J and Carvajal, C and Muñoz Venturelli, P}, title = {Post-COVID-19 condition: a sex-based analysis of clinical and laboratory trends.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1376030}, pmid = {38919940}, issn = {2296-858X}, abstract = {BACKGROUND AND AIM: Post-COVID-19 condition (PCC) encompasses long-lasting symptoms in individuals with COVID-19 and is estimated to affect between 31-67% of patients, with women being more commonly affected. No definitive biomarkers have emerged in the acute stage that can help predict the onset of PCC, therefore we aimed at describing sex-disaggregated data of PCC patients from a local cohort and explore potential acute predictors of PCC and neurologic PCC.

METHODS: A local cohort of consecutive patients admitted with COVID-19 diagnosis between June 2020 and July 2021 were registered, and clinical and laboratory data were recorded. Only those <65 years, discharged alive and followed up at 6 and 12 months after admission were considered in these analyses. Multivariable logistic regression analysis was performed to explore variables associated with PCC (STATA v 18.0).

RESULTS: From 130 patients in the cohort, 104 were contacted: 30% were women, median age of 42 years. At 6 months, 71 (68%) reported PCC symptoms. Women exhibited a higher prevalence of any PCC symptom (87 vs. 60%, p = 0.007), lower ferritin (p = 0.001) and procalcitonin (p = 0.021) and higher TNF levels (p = 0.042) in the acute phase compared to men. Being women was independently associated to 7.60 (95% CI 1.27-45.18, p = 0.026) higher risk for PCC. Moreover, women had lower return to normal activities 6 and 12 months.

CONCLUSION: Our findings highlight the lasting impact of COVID-19, particularly in young women, emphasising the need for tailored post-COVID care. The lower ferritin levels in women are an intriguing observation, warranting further research. The study argues for comprehensive strategies that address sex-specific challenges in recovery from COVID-19.}, } @article {pmid38918633, year = {2024}, author = {Khunti, K and Banerjee, A and Evans, RA and Calvert, M}, title = {Long COVID research in minority ethnic populations may be lost in translation.}, journal = {Nature medicine}, volume = {30}, number = {9}, pages = {2390-2391}, pmid = {38918633}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/epidemiology/ethnology/virology ; Ethnic and Racial Minorities ; *Post-Acute COVID-19 Syndrome ; Translational Research, Biomedical ; }, } @article {pmid38918517, year = {2024}, author = {Kim, S and Lee, H and Lee, J and Lee, SW and Kwon, R and Kim, MS and Koyanagi, A and Smith, L and Fond, G and Boyer, L and Rahmati, M and López Sánchez, GF and Dragioti, E and Cortese, S and Shin, JY and Choi, A and Suh, HS and Lee, S and Solmi, M and Min, C and Shin, JI and Yon, DK and Fusar-Poli, P}, title = {Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan.}, journal = {Nature human behaviour}, volume = {8}, number = {8}, pages = {1530-1544}, pmid = {38918517}, issn = {2397-3374}, support = {RS-2023-00248157//National Research Foundation of Korea (NRF)/ ; HI22C1976//Korea Health Industry Development Institute (KHIDI)/ ; 21153MFDS601//Ministry of Food and Drug Safety (MFDS)/ ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Republic of Korea/epidemiology ; Male ; Female ; Middle Aged ; Japan/epidemiology ; Adult ; Aged ; Cohort Studies ; Mental Disorders/epidemiology ; SARS-CoV-2 ; Risk Factors ; }, abstract = {We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.}, } @article {pmid38918248, year = {2024}, author = {Zeiler, K and Jämterud, SM and Bredström, A and Divanoglou, A and Levi, R}, title = {A Qualitative Phenomenological Philosophy Analysis of Affectivity and Temporality in Experiences of COVID-19 and Remaining Symptoms after COVID-19 in Sweden.}, journal = {The Journal of medical humanities}, volume = {}, number = {}, pages = {}, pmid = {38918248}, issn = {1573-3645}, abstract = {This article explores affectivity, temporality, and their interrelation in patients who contracted COVID-19 during the first wave of the pandemic in Sweden and with symptoms indicative of post-COVID-19 Condition (PCC) that remained one year after the infection. It offers a qualitative phenomenological philosophy analysis, showing how being ill with acute COVID-19 and with symptoms indicative of PCC can entail a radically altered self-world relation. We identify two examples of pre-intentional (existential) feelings: that of listlessness and that of not being able to sense what is real and not real, both of which, in different ways, imply a changed self-world relation. We offer an analysis of intentional feelings: how the fear of not "returning" to one's previous self and the hope of such a return weave together the present and the absent, as well as the past and the future, in ways that make the future appear as constricted, disquieting, or lost. We argue that a phenomenological differentiation among experiences of living with symptoms indicative of PCC-through attention to the way intentional affectivity and pre-intentional affectivity help shape the embodied self's attunement to the world-is apt to yield a better understanding of the variations within these experiences and contribute to clinical practice.}, } @article {pmid38917451, year = {2025}, author = {Besnier, F and Malo, J and Mohammadi, H and Clavet, S and Klai, C and Martin, N and Bérubé, B and Lecchino, C and Iglesies-Grau, J and Vincent, T and Gagnon, C and Gaudreau-Majeau, F and Juneau, M and Simard, F and L'Allier, P and Nigam, A and Gayda, M and Bherer, L}, title = {Effects of Cardiopulmonary Rehabilitation on Cardiorespiratory Fitness and Clinical Symptom Burden in Long COVID: Results From the COVID-Rehab Randomized Controlled Trial.}, journal = {American journal of physical medicine & rehabilitation}, volume = {104}, number = {2}, pages = {163-171}, doi = {10.1097/PHM.0000000000002559}, pmid = {38917451}, issn = {1537-7385}, mesh = {Humans ; Male ; *COVID-19/rehabilitation/physiopathology/complications ; Middle Aged ; Female ; *Cardiorespiratory Fitness/physiology ; *Quality of Life ; *Cardiac Rehabilitation/methods ; SARS-CoV-2 ; Exercise Therapy/methods ; Exercise Test ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; Symptom Burden ; }, abstract = {OBJECTIVE: The aim of the study is to investigate the effectiveness of an 8-wk cardiopulmonary rehabilitation program on cardiorespiratory fitness (VO 2 peak) and key cardiopulmonary exercise test measures, quality of life, and symptom burden in individuals with long COVID.

DESIGN: Forty individuals with long COVID (mean age 53 ± 11 yrs), were randomized into two groups: (1) rehabilitation group: center-based individualized clinical rehabilitation program (8 wks, 3 sessions per week of aerobic and resistance exercises, and daily inspiratory muscle training) and (2) control group: individuals maintained their daily habits during an 8-wk period.

RESULTS: There was a significant difference between groups in mean VO 2 peak improvement (P = 0.003). VO 2 peak improved significantly in the rehab group (+2.7 mL.kg.min; 95% CI = +1.6 to +3.8; P < 0.001) compared to the control group (+0.3 mL.kg.min; 95% CI = -0.8 to +1.3 P = 0.596), along with VE/VCO 2 slope (P = 0.032) (-2.4; 95% CI = -4.8 to +0.01; P = 0.049 and +1.3; 95% CI = -1.0 to +3.6; P = 0.272, respectively) and VO 2 at first ventilatory threshold (P = 0.045). Furthermore, all symptom impact scales improved significantly in the rehabilitation group compared to the control group (P < 0.05).

CONCLUSIONS: An individualized and supervised cardiopulmonary rehabilitation program was effective in improving cardiorespiratory fitness, ventilatory efficiency, and symptom burden in individuals with long COVID. Careful monitoring of symptoms is important to appropriately tailor and adjust rehabilitation sessions.}, } @article {pmid38916431, year = {2024}, author = {Epsi, NJ and Chenoweth, JG and Blair, PW and Lindholm, DA and Ganesan, A and Lalani, T and Smith, A and Mody, RM and Jones, MU and Colombo, RE and Colombo, CJ and Schofield, C and Ewers, EC and Larson, DT and Berjohn, CM and Maves, RC and Fries, AC and Chang, D and Wyatt, A and Scher, AI and Byrne, C and Rusiecki, J and Saunders, DL and Livezey, J and Malloy, A and Bazan, S and Maldonado, C and Edwards, MS and Mende, K and Simons, MP and O'Connell, RJ and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and Richard, SA}, title = {Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiae318}, pmid = {38916431}, issn = {1537-6613}, abstract = {BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints.

METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms.

RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms.

CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.}, } @article {pmid38916092, year = {2024}, author = {Glace, BW and Kremenic, IJ and Hogan, DE and Kwiecien, SY and McHUGH, MP}, title = {Habitual physical activity and COVID-19.}, journal = {The Journal of sports medicine and physical fitness}, volume = {64}, number = {7}, pages = {685-693}, doi = {10.23736/S0022-4707.24.15516-8}, pmid = {38916092}, issn = {1827-1928}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; *Exercise/physiology ; Adult ; SARS-CoV-2 ; Surveys and Questionnaires ; Hospitalization/statistics & numerical data ; Fatigue/physiopathology ; Aged ; }, abstract = {BACKGROUND: Physical activity (PA) is known to decrease COVID-19 risk factors and can attenuate symptoms of viral infections. However, difficulty exercising and fatigue are common complaints after COVID-19. It is unknown whether prior habitual PA will improve outcomes and what the time course is until full recovery of PA after COVID-19.

METHODS: Invitations were emailed to 21,933 adults who were SARS-CoV-2 positive between March 2020 and February 2021. Participants completed intake surveys and the Physical Activity History (PAH) questionnaire regarding PA during the 3-month prior to infection. Monthly thereafter, for up to 23 months, participants were emailed surveys. Scores were computed for moderate and heavy PA. Long COVID (LC) was defined as having recurring/persistent symptoms 9 months after diagnosis.

RESULTS: Overall, 993 patients completed the intake survey (age 50.7±15.8 years, BMI 27.3±9.2, 58% women); 28% had been hospitalized. One-third had recovered to their pre-infection level of PA at 9 months post-infection; this increased to 65% at one year, and 90% at two years. Higher pre-diagnosis PA reduced odds of hospitalization (P<0.05) but not of LC. Factors predictive of poor PA recovery were higher pre-diagnosis PA, shortness of breath and fatigue during acute illness, and fatigue chronically. Participants who reported ongoing symptoms had consistently poorer recovery of habitual PA compared to those not reporting chronic symptoms.

CONCLUSIONS: Habitual PA reduced odds of hospitalization but not of LC. Thirty-five percent had not returned to pre-COVID-19 levels of PA one year after infection, representing a major public health threat.}, } @article {pmid38915595, year = {2024}, author = {Yang, S and Datta, D and Krienen, FM and Ling, E and Woo, E and May, A and Anderson, GM and Galvin, VC and Gonzalez-Burgos, G and Lewis, DA and McCarroll, SA and Arnsten, AF and Wang, M}, title = {Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.13.598842}, pmid = {38915595}, issn = {2692-8205}, abstract = {Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, and have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may cause higher cognitive deficits in these disorders. The current study found that KYNA and its synthetic enzyme, KAT II, have greatly expanded expression in primate dlPFC in both glia and neurons. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys, suggesting a therapeutic avenue for the treatment of cognitive deficits in neuroinflammatory disorders.}, } @article {pmid38914852, year = {2024}, author = {Rueb, M and Ruzicka, M and Fonseca, GJI and Valdinoci, E and Benesch, C and Pernpruner, A and von Baum, M and Remi, J and Jebrini, T and Schöberl, F and Straube, A and Stubbe, HC and Adorjan, K}, title = {Headache severity in patients with post COVID-19 condition: a case-control study.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1935-1943}, pmid = {38914852}, issn = {1433-8491}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Adult ; Case-Control Studies ; Middle Aged ; *Headache/epidemiology ; *Severity of Illness Index ; Quality of Life ; Germany/epidemiology ; Post-Acute COVID-19 Syndrome ; Fatigue/etiology/epidemiology/physiopathology ; }, abstract = {Post COVID-19 conditions (PCC) present with a wide range of symptoms. Headache is one of the most frequently reported neurological symptoms by patients with PCC. We aimed to assess the prevalence of headache in patients with PCC who attended the Post-COVID[LMU] outpatient department at LMU University Hospital in Munich. We hypothesized that headaches occur more frequently in patients with PCC than in the control group. Patients answered a questionnaire containing sociodemographic characteristics, their current symptoms, and prior psychiatric and somatic diagnoses, the WHO Quality of Life assessment (WHOQOL-BREF), 9-item Patient Health Questionnaire (PHQ-9), and the Fatigue Severity Scale (FSS). 188 PCC patients were included in this study and compared to a control group of patients with a history of COVID-19 or a different infectious disease - but no consecutive post-infectious condition (nc=27). 115 (61%) of our PCC patients were female. The median age was 41 years. 60 (32%, p = 0.001) had a pre-existing psychiatric diagnosis. PCC was associated with worse outcomes in all four domains of the WHOQOL-BREF (p < 0.001), high levels of fatigue (FSS; p < 0.001), and a higher likeliness for symptoms of depression (PHQ-9; p < 0.001). We were able to confirm that psychiatric disorders are more frequently associated with headaches in PCC patients. Headache should be assessed and treated in the context of PCC not only by neurologists but by multi-professional teams and regarding all PCC symptoms.}, } @article {pmid38914457, year = {2025}, author = {Hunt, J}, title = {Will psychology ever 'join hands' with disability studies? Opportunities and challenges in working towards structurally competent and disability-affirmative psychotherapy for energy limiting conditions.}, journal = {Medical humanities}, volume = {50}, number = {4}, pages = {728-739}, doi = {10.1136/medhum-2023-012877}, pmid = {38914457}, issn = {1473-4265}, mesh = {Humans ; *Disabled Persons/psychology ; *Psychotherapy/methods ; COVID-19 ; Psychology ; Chronic Disease/therapy ; }, abstract = {Despite sustained efforts among critically informed scholars to integrate thinking from disability studies into psychology, the psy disciplines continue to largely neglect the lived experience of disabled people and overlook disability as a form of social inequity and valued culture. In this article, I make a renewed case for integrating thinking from disability studies into psy, in particular within the psychotherapy professions and in the case of 'energy limiting conditions', a grass-roots concept that includes clinically and socially marginalised chronic illness such as Long COVID. Drawing on my experience as a disabled practitioner, and situating this within extant literature on disability and psy, I take an autoethnographic approach to exploring opportunities and challenges in bridging the interdisciplinary divide. I argue that unacknowledged institutional ableism within psy reproduces and is reinforced by physical and attitudinal barriers for disabled practitioners and service users, engendering under-representation of disability in psychotherapy professions and lacunae in disability-affirmative conceptual resources. Additionally, I propose that hermeneutical lacunae are bolstered by documented defensive clinical practices pertaining to disability. After discussing a wealth of opportunities for integration offered by disability studies, and noting the institutional failure within psy to embrace disability-related demographic and epistemic diversity, I question whether ongoing epistemic and social exclusions within the psy disciplines constitute a case of 'willful epistemic ableism'. Drawing on theorising vis-à-vis epistemic injustice and epistemologies of ignorance, I signal a form of systematic, actively maintained and structurally incentivised (motivated) non-knowing that results in collective failure among dominant groups to recognise established hermeneutical resources of the disabled community and allies. I conclude with suggestions of how this form of epistemic injustice might be mitigated.}, } @article {pmid38914428, year = {2024}, author = {Hargrave, KL}, title = {Long covid: I'd rather have a well researched and well informed doctor than "become my own physician".}, journal = {BMJ (Clinical research ed.)}, volume = {385}, number = {}, pages = {q1398}, doi = {10.1136/bmj.q1398}, pmid = {38914428}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; SARS-CoV-2 ; Physicians/psychology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38912617, year = {2024}, author = {Pietrzak, P and Hanke, W}, title = {The long COVID and its mental health manifestations - the review of literature.}, journal = {International journal of occupational medicine and environmental health}, volume = {37}, number = {3}, pages = {360-380}, pmid = {38912617}, issn = {1896-494X}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; SARS-CoV-2 ; Depression/epidemiology ; Anxiety/epidemiology ; Mental Disorders/epidemiology ; Suicide, Attempted/statistics & numerical data/psychology ; Post-Acute COVID-19 Syndrome ; Mental Health ; Prevalence ; }, abstract = {This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental disorders such as depression, anxiety, rate of suicide attempts, and long COVID (LC) infections in the general population during COVID-19 pandemic. Analysis of the literature (in English, Polish and Spanish language) on topics related to COVID-19, mental disorders (suicide attempts, depression, anxiety) and LC infection published during the 4 years (2020-2023) was done using Pubmed and PubMed Central search engine. Keywords such as "COVID-19," "mental disorders," "long COVID infection," "depression," "anxiety," "suicide attempts" were used during the search. The conduct of this review/comment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, which corresponds to a checklist of 27 items designed to facilitate the development and reporting of a robust protocol for systematic reviews or meta-analyses. Overall 35 studies were selected and analyzed in the review on topics: including among others LC (14 studies), suicide attempts (7 studies), mental disorders (depression, anxiety) (14 studies). The main issues raised in the articles were: higher risk of LC symptoms in women, fatigue and brain fog listed as frequently encountered patient's complaints together with anxiety, depression, loneliness, especially in younger age groups and in women. Issues regarding LC, mental disorders and suicide attempts requires further research as the results vary in different countries. Int J Occup Med Environ Health. 2024;37(3):360-80.}, } @article {pmid38911850, year = {2024}, author = {Carvajal, JJ and García-Castillo, V and Cuellar, SV and Campillay-Véliz, CP and Salazar-Ardiles, C and Avellaneda, AM and Muñoz, CA and Retamal-Díaz, A and Bueno, SM and González, PA and Kalergis, AM and Lay, MK}, title = {New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1363572}, pmid = {38911850}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/immunology/epidemiology ; *SARS-CoV-2 ; Angiotensin-Converting Enzyme 2/metabolism ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.}, } @article {pmid38911448, year = {2024}, author = {Baker, S}, title = {New Long-Covid Randomized Controlled Study Offers Hope to Patients.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {23}, number = {2}, pages = {14-18}, pmid = {38911448}, issn = {1546-993X}, } @article {pmid38911226, year = {2024}, author = {Alim-Marvasti, A and Ciocca, M and Kuleindiren, N and Lin, A and Selim, H and Mahmud, M}, title = {Subjective brain fog: a four-dimensional characterization in 25,796 participants.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1409250}, pmid = {38911226}, issn = {1662-5161}, abstract = {IMPORTANCE: Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been systematically characterised.

OBJECTIVE: To characterise self-reported brain fog.

DESIGN: We systematically studied the cross-sectional associations between 29 a priori variables with the presence of "brain fog." The variables were grouped into four categories: demographics, symptoms and functional impairments, comorbidities and potential risk factors (including lifestyle factors), and cognitive score. Univariate methods determined the correlates of brain fog, with long-COVID and non-long-COVID subgroups. XGBoost machine learning model retrospectively characterised subjective brain fog. Bonferroni-corrected statistical significance was set at 5%.

SETTING: Digital application for remote data collection.

PARTICIPANTS: 25,796 individuals over the age of 18 who downloaded and completed the application.

RESULTS: 7,280 of 25,796 individuals (28.2%) reported experiencing brain fog, who were generally older (mean brain fog 35.7 ± 11.9 years vs. 32.8 ± 11.6 years, p < 0.0001) and more likely to be female (OR = 1.2, p < 0.001). Associated symptoms and functional impairments included difficulty focusing or concentrating (OR = 3.3), feeling irritable (OR = 1.6), difficulty relaxing (OR = 1.2, all p < 0.0001), difficulty following conversations (OR = 2.2), remembering appointments (OR = 1.9), completing paperwork and performing mental arithmetic (ORs = 1.8, all p < 0.0001). Comorbidities included long-COVID-19 (OR = 3.8, p < 0.0001), concussions (OR = 2.4, p < 0.0001), and higher migraine disability assessment scores (MIDAS) (+34.1%, all p < 0.0001). Cognitive scores were marginally lower with brain fog (-0.1 std., p < 0.001). XGBoost achieved a training accuracy of 85% with cross-validated accuracy of 74%, and the features most predictive of brain fog in the model were difficulty focusing and following conversations, long-COVID, and severity of migraines.

CONCLUSIONS AND RELEVANCE: This is the largest study characterising subjective brain fog as an impairment of concentration associated with functional impairments in activities of daily living. Brain fog was particularly associated with a history of long-COVID-19, migraines, concussion, and with 0.1 standard deviations lower cognitive scores, especially on modified Stroop testing, suggesting impairments in the ability to inhibit cognitive interference. Further prospective studies in unselected brain fog sufferers should explore the full spectrum of brain fog symptoms to differentiate it from its associated conditions.}, } @article {pmid38909338, year = {2024}, author = {Penrose, K and Srivastava, A and Shen, Y and Robertson, MM and Kulkarni, SG and Allen, KE and Porter, TM and Puzniak, L and McLaughlin, JM and Nash, D}, title = {Perceived Risk for Severe COVID-19 and Oral Antiviral Use Among Antiviral-Eligible US Adults.}, journal = {Infectious diseases and therapy}, volume = {13}, number = {8}, pages = {1743-1757}, pmid = {38909338}, issn = {2193-8229}, abstract = {INTRODUCTION: Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low for reasons that are not entirely understood. Our study aimed to assess the association between perceived risk for severe COVID-19 outcomes and oral antiviral use among those who were eligible for treatment based on Centers for Disease Control and Prevention (CDC) guidelines.

METHODS: We surveyed 4034 non-institutionalized US adults in April 2023, and report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 and no current long COVID symptoms. Survey weights were used to yield nationally representative estimates. The primary exposure of interest was whether participants perceived themselves to be "at high risk for severe COVID-19." The primary outcome was use of a COVID-19 oral antiviral within 5 days of suspected SARS-CoV-2 infection.

RESULTS: Only 18.5% of antiviral-eligible adults considered themselves to be at high risk for severe COVID-19 and 16.8% and 15.9% took oral antivirals at any time or within 5 days of SARS-CoV-2 infection, respectively. In contrast, 79.8% were aware of antiviral treatments for COVID-19. Perceived high-risk status was associated with being more likely to be aware (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03-1.20]), to be prescribed (aPR 1.47 [95% CI 1.08-2.01]), and to take oral antivirals at any time (aPR 1.61 [95% CI 1.16-2.24]) or within 5 days of infection (aPR 1.72 [95% CI 1.23-2.40]).

CONCLUSIONS: Despite widespread awareness of the availability of COVID-19 oral antivirals, more than 80% of eligible US adults did not receive them. Our findings suggest that differences between perceived and actual risk for severe COVID-19 (based on current CDC guidelines) may partially explain this low uptake.}, } @article {pmid38904974, year = {2024}, author = {Rocker, J and Weiss, C}, title = {COVID-19, MIS-C, and long COVID in pediatric patients: an update.}, journal = {Pediatric emergency medicine practice}, volume = {21}, number = {7}, pages = {1-28}, pmid = {38904974}, issn = {1549-9669}, mesh = {Humans ; *COVID-19/complications/therapy ; *Systemic Inflammatory Response Syndrome/therapy/diagnosis ; Child ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19, the disease caused by SARS-CoV-2, has been disruptive worldwide. It was primarily a respiratory disease that affected many of the medically vulnerable, but the true impact of postacute sequelae of SARS-CoV-2 (PASC), which has been demonstrated to involve all organ systems, is now coming to light. In addition, a new disease entity emerged, multisystem inflammatory syndrome in children (MIS-C), which has had significant morbidity and mortality associated with it. This issue reviews the presentation, evaluation, and management of patients with COVID-19, MIS-C, and PASC. Additionally, the current literature supporting public health measures, as well as COVID-19 vaccinations and their complications are discussed.}, } @article {pmid38904142, year = {2024}, author = {Wentz, E and Ni, Z and Yenokyan, K and Vergara, C and Pahwa, J and Kammerling, T and Xiao, P and Duggal, P and Lau, B and Mehta, SH}, title = {Cohort profile: the Johns Hopkins COVID Long Study (JHCLS)-a US nationwide prospective cohort study.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e077742}, pmid = {38904142}, issn = {2044-6055}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Prospective Studies ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; United States/epidemiology ; Aged ; Hospitalization/statistics & numerical data ; Young Adult ; Self Report ; Health Status ; }, abstract = {PURPOSE: COVID-19 continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short-term and long-term consequences of COVID-19 in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey.

PARTICIPANTS: 16 764 adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey.

FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16 764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a very good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported hospitalisation and 63% were defined as having long COVID using the WHO definition.

FUTURE PLANS: Analysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.}, } @article {pmid38904135, year = {2024}, author = {Miller, A and Song, N and Sivan, M and Chowdhury, R and Burke, MR}, title = {Identifying the needs of people with long COVID: a qualitative study in the UK.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e082728}, pmid = {38904135}, issn = {2044-6055}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; United Kingdom ; *Qualitative Research ; *COVID-19/epidemiology ; *Focus Groups ; Needs Assessment ; SARS-CoV-2 ; Young Adult ; Post-Acute COVID-19 Syndrome ; Health Services Needs and Demand ; }, abstract = {OBJECTIVES: To identify the needs of people with long COVID (LC) in the UK.

DESIGN: Qualitative study using the Framework Analysis to analyse focus group discussions.

PARTICIPANTS: 25 adults with LC aged 19-76 years including 17 men and 8 women. Average disease duration was 80.1 weeks.

SETTING: Eight focus groups were conducted in April 2023 online and in-person at the University of Leeds (UoL), UK. Recruitment routes included advertisement via Leeds Community Healthcare services, the English National Opera Breathe Programme and within the UoL.

RESULTS: Three key themes/needs were identified. (Theme 1) Support systems including community groups, disability benefits, clinical services and employment support should be accessible and tailored to the needs of people with LC. (Theme 2) Research should investigate the physiology of symptoms, new clinical tests and treatment interventions to improve clinical understanding of the condition and symptom management. (Theme 3) Societal awareness should be promoted via local and national initiatives to educate the public about the condition and reduce stigma.

CONCLUSIONS: Participants experienced varied and individual challenges to daily life due to LC. There is a need for government acknowledgement of LC as a disability to ensure people with LC have access to disability support and legal protection. Policy development should be patient-driven and acknowledge the individual needs of people with LC in order to improve their quality of life.}, } @article {pmid38903385, year = {2024}, author = {Bohlen, B and Franzen, D}, title = {Cardiac Damage After SARS-CoV2 Infection.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60641}, pmid = {38903385}, issn = {2168-8184}, abstract = {COVID-19 is a viral disease that can manifest acutely in the respiratory tract and other organs. In this study, we aimed to investigate potential long-term damage to the heart from COVID-19. For this study, we divided 97 consecutive unselected COVID-19 patients aged 18-80 years at a cardiology practice in Cologne, Germany, into two groups based on the severity of their infection. We performed a resting ECG and a resting transthoracic echocardiography three and six months after SARS-CoV2 infection. The key discriminator determining disease severity was bed confinement or hospital admission. Group 1 included patients with less severe COVID-19, whereas group 2 contained more severe cases. Heart rate as the primary ECG endpoint was lower by a statistically significant amount for the entire study population (p=0.024), subdivided by gender (pwomen <0.001, pmen <0.001) and in group 1 p =0.003 compared to three months. QTc time and repolarization disturbances as primary ECG endpoints and the echocardiographic primary endpoints, left ventricular ejection fraction, and left ventricular end-diastolic diameter (LVEDD), showed no relevant difference between the subgroups at three and six months or between the measurements taken at each point. In contrast, LVEDD normalized to body surface area was statistically significantly lower at six months in women in group 1 compared to group 2 (p=0.048) and in the overall study population at six months compared with the data after three months (p=0.034). E/E' was statistically lower at six months than at three months in the whole population (p=0.004) and in women (p=0.031). All measured echocardiographic and electrocardiographic mean values were within the normal range in all groups and follow-up controls. Overall, the prospective study conducted showed no significant evidence of long-term cardiac damage from COVID-19 disease, as evidenced by electrocardiographic and echocardiographic examinations at three and six months after infection.}, } @article {pmid38903009, year = {2024}, author = {Rutsch, M and Buhr-Schinner, H and Gross, T and Schüller, PO and Deck, R}, title = {Pulmonary rehabilitation in follow-up and inpatient rehabilitation for Long COVID: twelve months of follow-up.}, journal = {European journal of physical and rehabilitation medicine}, volume = {60}, number = {4}, pages = {716-728}, pmid = {38903009}, issn = {1973-9095}, mesh = {Humans ; *COVID-19/rehabilitation ; Female ; Male ; Middle Aged ; Adult ; Germany ; *Quality of Life ; Follow-Up Studies ; Longitudinal Studies ; Prospective Studies ; Aged ; SARS-CoV-2 ; Rehabilitation Centers ; Pandemics ; Adolescent ; Inpatients ; }, abstract = {BACKGROUND: Individuals with persistent impairments due to Coronavirus disease 2019 (COVID-19) can receive pulmonary rehabilitation in Germany. To date, there is no evidence of the medium- or long-term effects of pulmonary rehabilitation on Long COVID.

AIM: This study examined changes in health and occupational outcomes over time and described the therapeutic content of pulmonary rehabilitation and aftercare. This analysis also compared two rehabilitation groups after COVID-19 who had different levels of access to rehabilitation.

DESIGN: Longitudinal observational study with multicenter and prospective data collection.

SETTING: Pulmonary rehabilitation in four different rehabilitation facilities in Germany.

POPULATION: Individuals with a mild course of disease and long-lasting impairments (inpatient rehabilitation, IR) and patients with a severe course after hospitalization (follow-up rehabilitation, FuR). Participants had to be between 18 and 65 years of age.

METHODS: Written questionnaires were administered at the beginning and end of rehabilitation, as well as six and twelve months after rehabilitation. Health-related quality of life (HrQoL), fatigue, participation restrictions, COVID-19 symptoms, mental and physical health were assessed, as well as occupational outcomes and questions about rehabilitation and aftercare.

RESULTS: IR patients were predominantly female (68.0%) and 52 years of age on average, while 66.1% of Long COVID rehabilitees in FuR were male and three years older. Over the course of rehabilitation, most COVID-19 symptoms decreased with statistical significance. The subjective health scales showed improvements with medium to large effect sizes (ES) over time in IR (P<0.01; ES between 0.55 (cognitive fatigue) and 1.40 (physical fatigue)) and small to large effects in FuR (P<0.01; ES between 0.45 (anxiety) and 1.32 (physical fatigue)). One year after rehabilitation, most effects remained at a moderate level. After twelve months, an increase in neurocognitive symptoms was observed in FuR patients. More than 80% of employed people returned to work one year after rehabilitation, although FuR patients returned to work a median of four weeks later (P<0.01).

CONCLUSIONS: The comparative analysis showed that rehabilitees in different forms of rehabilitation attended rehabilitation with different impairments and rehabilitation goals, which are partly considered in treatment and aftercare.

To provide needs-based rehabilitation to different rehabilitation groups with Long COVID, knowledge of their health histories and preferences is necessary.}, } @article {pmid38902726, year = {2024}, author = {Lin, LY and Henderson, AD and Carlile, O and Dillingham, I and Butler-Cole, BFC and Marks, M and Briggs, A and Jit, M and Tomlinson, LA and Bates, C and Parry, J and Bacon, SCJ and Goldacre, B and Mehrkar, A and MacKenna, B and , and Eggo, RM and Herrett, E}, title = {Healthcare utilisation in people with long COVID: an OpenSAFELY cohort study.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {255}, pmid = {38902726}, issn = {1741-7015}, support = {MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; MR/V015737/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Male ; Female ; *Patient Acceptance of Health Care/statistics & numerical data ; Middle Aged ; *COVID-19/epidemiology/therapy ; Cohort Studies ; Aged ; Adult ; England/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged, 80 and over ; Health Care Costs/statistics & numerical data ; Young Adult ; State Medicine/economics/statistics & numerical data ; }, abstract = {BACKGROUND: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined.

METHODS: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records.

RESULTS: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60-£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group.

CONCLUSIONS: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.}, } @article {pmid38902696, year = {2024}, author = {Sun, Y and Sun, J and Chen, X and Wang, Y and Gao, X}, title = {EEG signatures of cognitive decline after mild SARS-CoV-2 infection: an age-dependent study.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {257}, pmid = {38902696}, issn = {1741-7015}, mesh = {Humans ; *COVID-19/physiopathology ; *Electroencephalography ; Child ; Adolescent ; Male ; *Cognitive Dysfunction/physiopathology/etiology/virology ; Female ; Young Adult ; Cohort Studies ; Age Factors ; Adult ; *SARS-CoV-2 ; Child, Preschool ; Brain/physiopathology/virology ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: Current research on the neurological impact of SARS-CoV-2 primarily focuses on the elderly or severely ill individuals. This study aims to explore the diverse neurological consequences of SARS-CoV-2 infection, with a particular focus on mildly affected children and adolescents.

METHODS: A cohort study was conducted to collect pre- and post-infection resting-state electroencephalogram (EEG) data from 185 participants and 181 structured questionnaires of long-term symptoms across four distinct age groups. The goal was to comprehensively evaluate the impact of SARS-CoV-2 infection on these different age demographics. The study analyzed EEG changes of SARS-CoV-2 by potential biomarkers across age groups using both spatial and temporal approaches.

RESULTS: Spatial analysis indicated that children and adolescents exhibit smaller changes in brain network and microstate patterns post-infection, implying a milder cognitive impact. Sequential linear analyses showed that SARS-CoV-2 infection is associated with a marked rise in low-complexity, synchronized neural activity within low-frequency EEG bands. This is evidenced by a significant increase in Hjorth activity within the theta band and Hjorth mobility in the delta band. Sequential nonlinear analysis indicated a significant reduction in the Hurst exponent across all age groups, pointing to increased chaos and complexity within the cognitive system following infection. Furthermore, linear regression analysis based on questionnaires established a significant positive relationship between the magnitude of changes in these neural indicators and the persistence of long-term symptoms post-infection.

CONCLUSIONS: The findings underscore the enduring neurological impacts of SARS-CoV-2 infection, marked by cognitive decline and increased EEG disarray. Although children and adolescents experienced milder effects, cognitive decline and heightened low-frequency electrical activity were evident. These observations might contribute to understanding potential anxiety, insomnia, and neurodevelopmental implications.}, } @article {pmid38902672, year = {2024}, author = {Rojas, NK and De Stavola, BL and Norris, T and Cortina-Borja, M and Nugawela, MD and Hargreaves, D and Dalrymple, E and McOwat, K and Simmons, R and Stephenson, T and Shafran, R and , and Pereira, SMP}, title = {Developing survey weights to ensure representativeness in a national, matched cohort study: results from the children and young people with Long Covid (CLoCk) study.}, journal = {BMC medical research methodology}, volume = {24}, number = {1}, pages = {134}, pmid = {38902672}, issn = {1471-2288}, support = {COVLT0022//NIHR and UKRI/ ; COVLT0022//NIHR and UKRI/ ; MR/P020372/1//UK Medical Research Council/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Child ; Adolescent ; Female ; *SARS-CoV-2 ; Male ; Cohort Studies ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; Logistic Models ; Child, Preschool ; Prevalence ; Young Adult ; }, abstract = {BACKGROUND: Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP.

METHODS: Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall 'envisioned population' survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census.

RESULTS: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings.

CONCLUSIONS: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.}, } @article {pmid38901797, year = {2024}, author = {Kattner, AA}, title = {And those who were seen dancing: Human interactions with fungi and vice versa.}, journal = {Biomedical journal}, volume = {47}, number = {3}, pages = {100755}, pmid = {38901797}, issn = {2320-2890}, mesh = {Humans ; *Fungi ; COVID-19 ; }, abstract = {This issue of the Biomedical Journal features a special section exploring mycobiota. Three articles examine the role of fungi in common metabolic disorders in, Clostridium difficile infection, and in immunocompromised patients. Additionally, the potential and challenges of the metaverse in healthcare are reviewed, alongside a holistic approach to improve patient outcomes in pancreatic cancer. In this issue also possible mechanism contributing to long COVID are discussed, as well as biomarkers that effectively predict sepsis outcomes, and key targets in osteosarcoma progression. Moreover, factors leading to peri-intubation cardiac arrest are analyzed, healthcare strategies from various regions are employed to predict cardiovascular events in Asian populations, two approaches to cavernous sinus dural arteriovenous fistula are compared, and a combination therapy against soft tissue sarcoma is presented.}, } @article {pmid38901570, year = {2024}, author = {Provenzale, G and Barbieri, L and Tumminello, G and Carugo, S and Guazzi, M}, title = {Exercise response in post-acute coronary syndrome patients survived to COVID-19 infection.}, journal = {International journal of cardiology}, volume = {411}, number = {}, pages = {132285}, doi = {10.1016/j.ijcard.2024.132285}, pmid = {38901570}, issn = {1874-1754}, mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology ; Male ; *Acute Coronary Syndrome/physiopathology ; Female ; Middle Aged ; Cross-Sectional Studies ; Aged ; *Exercise Test/methods ; Case-Control Studies ; *Exercise Tolerance/physiology ; Oxygen Consumption/physiology ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; }, abstract = {AIMS: Many studies evaluated the functional response in post-Covid-19 patients; however, they systematically excluded patients with concomitant acute coronary syndrome (ACS). We evaluated the long-term functional capacity assessed by cardiopulmonary exercise test (CPET) in patients hospitalized for ACS and concomitant SARS-CoV2 infection. The secondary aim was to investigate the functional response in patients with symptoms related to "long COVID-19 syndrome" (LCS).

METHODS: This cross-sectional case-control study compared 20 patients with ACS and concomitant SARS-COV2 infection with 20 patients without COVID-19. At the follow-up visit (between 6 and 12 months after revascularization procedure) all patients underwent a CPET.

RESULTS: Patients with previous ACS and concomitant COVID-19 showed a reduced O2 consumption than controls (predicted peak V̇O2 74.00% vs 86.70%; p = 0.01) with a high degree of ventilatory inefficiency (VE/ V̇CO2 slope 38.04 vs 30.31; p = 0.002). 50% of subjects with previous COVID-19 disease showed symptoms related to "LCS"; this subgroup demarcates the characteristic reduced exercise capacity found in the entire COVID + group.

CONCLUSIONS: This study is the first in literature having analyzed the long-term functional capacity phenotype in a population of ACS patients and concomitant SARS-CoV2 infection. Severe ventilatory inefficiency emerged as the functional signature of these patients. Moreover, the subset of patients with symptoms related to LCS has the most compromised long term reduced exercise capacity and an altered ventilation control.}, } @article {pmid38901177, year = {2024}, author = {Duricka, D and Liu, L}, title = {Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study.}, journal = {Autonomic neuroscience : basic & clinical}, volume = {254}, number = {}, pages = {103195}, doi = {10.1016/j.autneu.2024.103195}, pmid = {38901177}, issn = {1872-7484}, mesh = {Humans ; Retrospective Studies ; *COVID-19/complications ; *Stellate Ganglion ; Male ; *Autonomic Nerve Block/methods ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; Adult ; }, abstract = {The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as "Long COVID" or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021-2022) in our clinic. Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection. This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.}, } @article {pmid38901051, year = {2024}, author = {Mackay, A}, title = {The long COVID conundrum from a New Zealand perspective.}, journal = {The New Zealand medical journal}, volume = {137}, number = {1597}, pages = {79-85}, doi = {10.26635/6965.6419}, pmid = {38901051}, issn = {1175-8716}, mesh = {Humans ; New Zealand/epidemiology ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38900132, year = {2024}, author = {Sunami, Y and Sugaya, K and Takahashi, K}, title = {G protein-coupled receptors related to autoimmunity in postural orthostatic tachycardia syndrome.}, journal = {Immunological medicine}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/25785826.2024.2370079}, pmid = {38900132}, issn = {2578-5826}, abstract = {Postural orthostatic tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia in the absence of orthostatic hypotension. The pathophysiology of POTS may involve hypovolemia, autonomic neuropathy, a hyperadrenergic state, and cardiovascular deconditioning, any of which can co-occur in the same patient. Furthermore, there is growing evidence of the role of autoimmunity in a subset of POTS cases. In recent years, investigators have described an increased rate of autoimmune comorbidities as evidenced by the finding of several types of neural receptor autoantibody and non-specific autoimmune marker in patients with POTS. In particular, the association of the disease with several types of anti-G protein-coupled receptor (GPCR) antibodies and POTS has frequently been noted. A previous study reported that autoantibodies to muscarinic AChRs may play an important role in POTS with persistent, gastrointestinal symptoms. To date, POTS is recognized as one of the sequelae of coronavirus disease 2019 (COVID-19) and its frequency and pathogenesis are still largely unknown. Multiple autoantibody types occur in COVID-related, autonomic disorders, suggesting the presence of autoimmune pathology in these disorders. Herein, we review the association of anti-GPCR autoantibodies with disorders of the autonomic nervous system, in particular POTS, and provide a new perspective for understanding POTS-related autoimmunity.}, } @article {pmid38900060, year = {2024}, author = {Johnson, SM and Penner, J and Issitt, R and Kmentt, L and Grant, K and Pandey, A and Champsas, D and Abdel-Mannan, O and Maillard, S and McKenzie, K and Golding, E and Kucera, F and Hacohen, Y and Moshal, K}, title = {One- and Two-year Multidisciplinary Follow-Up of MIS-C at a Tertiary Hospital: A Retrospective Cohort Study.}, journal = {The Pediatric infectious disease journal}, volume = {43}, number = {10}, pages = {980-986}, doi = {10.1097/INF.0000000000004430}, pmid = {38900060}, issn = {1532-0987}, support = {FS/19/52/34563/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/complications ; Child ; Male ; Female ; *Tertiary Care Centers/statistics & numerical data ; Retrospective Studies ; *Systemic Inflammatory Response Syndrome/diagnosis/epidemiology ; Follow-Up Studies ; *SARS-CoV-2 ; United Kingdom/epidemiology ; Adolescent ; Hospitalization/statistics & numerical data ; }, abstract = {BACKGROUND: Although 6-month follow-up of patients with multisystem inflammatory syndrome in children (MIS-C) was reassuring, there is scant data on long-term sequelae, including whether changing variants affect clinical severity and outcomes.

METHODS: Children (<18 years of age) admitted to Great Ormond Street Hospital between April 4, 2020, and January 2023, meeting diagnostic criteria for MIS-C were included. Admission and follow-up data were categorized by the predominant SARS-CoV-2 circulating variant in the United Kingdom.

RESULTS: One hundred and sixty children [median age, 10.1 (interquartile range, 7.9-12.6) years] were included. There was no difference in the time of symptom onset to diagnosis between waves (P =0.23) or hospitalization days across all waves (P =0.32). Inflammatory markers were normal for up to 2 years in all patients except one. Eleven patients (6.9%) remain in follow-up: cardiology (n=5), gastroenterology (n=5) and nephrology (n=1). The main self-reported symptoms at 2 years were abdominal pain (n=5) and myalgia (n=2). Fatigue was present in approximately a quarter of patients at admission; this reduced to 14 (9%), (2%) and 1 (2%) at 6-month, 1-year and 2-year follow-ups, respectively. Chronic fatigue or long-COVID symptomatology was rare (n=1) even with high rates of concurrent Epstein-Barr virus positivity (49/134). All patients had sustained neurological recovery with no new neurological pathology observed.

CONCLUSIONS: Patients with MIS-C have a sustained recovery, which is reassuring for positive long-term outcomes. Across waves, time from symptom onset to diagnosis and treatment, symptomatology and length of stay were similar. Sustained recovery is reassuring for clinicians and parents alike. Differentiating long-COVID symptomatology from that of MIS-C is important in formulating an individualized treatment plan.}, } @article {pmid38899432, year = {2024}, author = {Tang, Y and Zou, X and Liu, P and Dai, Y and Wang, S and Su, X and Yu, Y and Tang, W and Zhou, J and Li, C and Mei, H and Xiao, N and Ou, Y and Wang, J and Lu, G and Lin, G and Cheng, L}, title = {Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID.}, journal = {Journal of medical virology}, volume = {96}, number = {6}, pages = {e29757}, doi = {10.1002/jmv.29757}, pmid = {38899432}, issn = {1096-9071}, support = {2020SK3016//The Emergency Projects for COVID-19 by the Science and Technology Department of Hunan Province/ ; 2023SK2001//The Emergency Projects for COVID-19 by the Science and Technology Department of Hunan Province/ ; }, mesh = {Humans ; *COVID-19/therapy/immunology ; *Mesenchymal Stem Cell Transplantation/methods ; Male ; Female ; Middle Aged ; *Umbilical Cord/cytology ; Mesenchymal Stem Cells ; Aged ; Treatment Outcome ; Adult ; SARS-CoV-2 ; T-Lymphocytes, Regulatory/immunology ; B-Lymphocytes/immunology ; Interleukin-6/blood ; }, abstract = {No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.}, } @article {pmid38899267, year = {2024}, author = {Singh, MM and Sharma, H and Bhatnagar, N and Borle, AL and Rao, S and Mishra, S and Singh, G and Singh, T and Kapoor, M and Kumar, N}, title = {Burden of Long COVID-19 in a Cohort of Recovered COVID-19 Patients in Delhi, India.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60652}, pmid = {38899267}, issn = {2168-8184}, abstract = {BACKGROUND: The long COVID phase is characterized by signs and symptoms persisting for at least three months after recovery from acute COVID-19 illness. There is limited data on comprehensive long-term clinical follow-up of COVID-19 patients.

AIMS: This study aims to explore the burden and symptomatology of long COVID syndrome and its association with various health parameters.

SETTINGS AND DESIGN: This prospective observational study was conducted in Delhi from May 2022 to March 2023.

METHODS AND MATERIAL: A total of 553 adult patients who had recovered from COVID-19 were enrolled in the study. A sociodemographic and clinical profile was obtained using validated questionnaires, along with an evaluation of biochemical parameters to assess the associated factors.

STATISTICAL ANALYSIS USED: Chi-square test, unpaired t-test, and bivariate regression analysis were applied using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY). A p value of <0.05 was considered significant.

RESULTS: A total of 252 patients (45.6%) had long COVID syndrome, which was significantly associated with the presence of any pre-existing comorbidity (OR=1.46 (1.02-2.09); p=0.039), previous history of hypertension (OR=1.82 (1.07-3.09); p=0.027), and vaccination against COVID-19 (OR=1.392 (1.171-1.656); p=0.003). The most common symptoms reported were persistent fatigue (33.3%) and persistent dry cough (28.5%). Patients with long COVID syndrome are also reported to have poorer sleep quality. Biochemical findings showed abnormal T lymphocytes (9.3%) and raised HbA1c (11.9%).

CONCLUSIONS: Multiple risk factors and symptoms associated with long COVID syndrome were identified in this study. Research efforts and knowledge regarding the pattern of illness will aid in long-term monitoring and development of interventional strategies and guidelines for the care of recovered COVID-19 patients.}, } @article {pmid38898594, year = {2024}, author = {Kalfas, M and Jolley, C and Hart, N and Rafferty, GF and Duncan, EL and Nicholson, T and Ashworth, M and Brewin, D and Barrett, B and Witard, OC and Ridge, D and Chalder, T}, title = {Exploring the Experiences of Living With the Post-COVID Syndrome: A Qualitative Study.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {3}, pages = {e14108}, pmid = {38898594}, issn = {1369-7625}, support = {COV210803//Guy's and St Thomas' Charity/ ; }, mesh = {Humans ; Female ; Male ; *Qualitative Research ; *COVID-19/psychology ; Middle Aged ; *Quality of Life ; Adult ; United Kingdom ; Aged ; Post-Acute COVID-19 Syndrome ; Interviews as Topic ; SARS-CoV-2 ; Sex Factors ; }, abstract = {INTRODUCTION: Many people experience persistent symptoms for more than 12 weeks following SARS-CoV-2 infection, which is known as post-COVID-19 condition (PCS) or Long COVID (LC). PCS can impair people's quality of life and daily functioning. However, there is a lack of in-depth research exploring the PCS patient journey, as well as gendered aspects of patients' experiences.

METHODS: Nineteen semi-structured qualitative interviews were conducted with people living with PCS in the United Kingdom (13 women, 6 men). Interviews were transcribed verbatim and analysed inductively using reflexive thematic analysis.

RESULTS: Five main themes were identified: 'Symptom dismissal', 'Lack of information and support', 'Life before and after Long COVID', 'Psychological impact' and 'Acceptance'. A shift overtime to self-management of symptoms was evident. These themes represent different stages of patients' PCS journey. Narratives indicated that women highlighted dismissal by healthcare professionals (HCPs), which was not as prominent in men's narratives. In addition, women went into more detail about the psychological impact of PCS compared to men.

CONCLUSION: Women with PCS reported symptom dismissal by HCPs, which may have delayed their diagnosis and negatively affected their well-being. We were not able to explore the experiences of people from non-conforming gender groups. Raising awareness of these issues among HCPs, particularly general practitioners, could improve patient care in PCS.

Patient and public involvement consisted of people who took part in the interviews and commented on the themes' interpretation and study conclusions.}, } @article {pmid38895641, year = {2024}, author = {Ach, T and Ben Haj Slama, N and Gorchane, A and Ben Abdelkrim, A and Garma, M and Ben Lasfar, N and Bellazreg, F and Debbabi, W and Hachfi, W and Chadli Chaieb, M and Zaouali, M and Letaief, A and Ach, K}, title = {Response to Letter to the Editor From Josef Finsterer: "Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis".}, journal = {Journal of the Endocrine Society}, volume = {8}, number = {7}, pages = {bvae087}, pmid = {38895641}, issn = {2472-1972}, } @article {pmid38893693, year = {2024}, author = {Song, X and Song, W and Cui, L and Duong, TQ and Pandy, R and Liu, H and Zhou, Q and Sun, J and Liu, Y and Li, T}, title = {A Comprehensive Review of the Global Epidemiology, Clinical Management, Socio-Economic Impacts, and National Responses to Long COVID with Future Research Directions.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {38893693}, issn = {2075-4418}, abstract = {Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID's epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management; Conclusions: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Addressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.}, } @article {pmid38892564, year = {2024}, author = {Tomasa-Irriguible, TM and Monfà, R and Miranda-Jiménez, C and Morros, R and Robert, N and Bordejé-Laguna, L and Vidal, S and Torán-Monserrat, P and Barriocanal, AM}, title = {Preventive Intake of a Multiple Micronutrient Supplement during Mild, Acute SARS-CoV-2 Infection to Reduce the Post-Acute COVID-19 Condition: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892564}, issn = {2072-6643}, support = {IIR IMP 21806//IGTP-HUGTP/ ; }, mesh = {Humans ; Female ; *COVID-19/prevention & control/epidemiology/complications ; Male ; Double-Blind Method ; Middle Aged ; *Dietary Supplements ; *Micronutrients/administration & dosage ; *SARS-CoV-2 ; Adult ; Spain/epidemiology ; Post-Acute COVID-19 Syndrome ; Aged ; Betacoronavirus ; }, abstract = {Patients hospitalized with COVID-19 have low levels of vitamins and trace elements. This could lead to a post-acute COVID-19 condition (PCC) that can worsen a patient's quality of life. We aimed to study the baseline micronutrient status of patients and assess whether a multiple micronutrient supplement (MMS) taken for 2 weeks at the first sign of COVID-19 symptoms would be able to reduce the incidence of PCC. This double-blind, placebo-controlled, randomized clinical trial was conducted in adult outpatients with acute COVID-19, recruited between 2021 and 2023 in Spain. Of the 285 patients assessed for eligibility, 267 were randomized and 246 were included in the intent-to-treat population. The mean age was 46.8 years, and 68% were female. Overall, 54.6% had micronutrient deficiencies in the acute phase of COVID-19 at baseline, and 26.2% had PCC after 180 days of follow-up (D180). The most frequently recorded PCC symptoms were neurological (14.1%), with 24% patients scoring worse in the cognitive tests compared to their baseline status. The rate of PCC at D180 was similar between the placebo (25.0%) and intervention (27.7%) groups, without significant differences (p = 0.785). Age over 50 years was the most relevant risk factor for developing PCC, followed by female sex. The most important protective factor against PCC was SARS-CoV-2 vaccination. In this population of predominantly middle-aged, white women with acute COVID-19 not requiring hospital admission, MMS intake for 14 days at symptom onset did not prevent PCC nor improve their micronutrient status at D180.}, } @article {pmid38892479, year = {2024}, author = {Jurek, JM and Castro-Marrero, J}, title = {A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892479}, issn = {2072-6643}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy ; *Gastrointestinal Microbiome ; *COVID-19/complications/immunology ; *Probiotics/therapeutic use ; *Dysbiosis ; SARS-CoV-2 ; Dietary Supplements ; Synbiotics/administration & dosage ; Brain-Gut Axis ; }, abstract = {Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), and long COVID are complex, multisystemic and long-term disabling conditions characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and long COVID suggest that the use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis, may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation and neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and long COVID.}, } @article {pmid38892110, year = {2024}, author = {Paroli, M and Gioia, C and Accapezzato, D and Caccavale, R}, title = {Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892110}, issn = {1422-0067}, mesh = {Animals ; Humans ; Autoimmune Diseases/immunology/complications ; *Autoimmunity ; *COVID-19/immunology/complications/virology ; *Fibromyalgia/immunology ; *Inflammation/immunology ; SARS-CoV-2/immunology ; }, abstract = {Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.}, } @article {pmid38890133, year = {2024}, author = {Goldenberg, JZ and Wright, TJ and Batson, RD and Wexler, RS and McGovern, KA and Venugopal, NK and Ward, WW and Randolph, KM and Urban, RJ and Pyles, RB and Sheffield-Moore, M}, title = {What is the association between the microbiome and cognition? An umbrella review protocol.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e077873}, pmid = {38890133}, issn = {2044-6055}, mesh = {Humans ; *Systematic Reviews as Topic ; *Cognitive Dysfunction/microbiology ; Cognition ; Microbiota ; Dysbiosis ; Research Design ; Alzheimer Disease/microbiology ; COVID-19/psychology ; Parkinson Disease/microbiology ; }, abstract = {INTRODUCTION: Cognitive impairment is reported in a variety of clinical conditions including Alzheimer's disease, Parkinson's and 'long-COVID'. Interestingly, many of these clinical conditions are also associated with microbial dysbiosis. This comanifestation of cognitive and microbiome findings in seemingly unrelated maladies suggests that they could share a common mechanism and potentially presents a treatment target. Although a rapidly growing body of literature has documented this comorbid presentation within specific conditions, an overview highlighting potential parallels across healthy and clinical populations is lacking. The objective of this umbrella review, therefore, is to summarise and synthesise the findings of these systematic reviews.

METHODS AND ANALYSIS: On 2 April 2023, we searched MEDLINE (Pubmed), Embase (Ovid), the Web of Science (Core Collection), the Cochrane Library of Systematic Reviews and Epistemonikos as well as grey literature sources, for systematic reviews on clinical conditions and interventions where cognitive and microbiome outcomes were coreported. An updated search will be conducted before completion of the project if the search-to-publication date is >1 year old. Screening, data abstraction and quality assessment (AMSTAR 2, A MeaSurement Tool to Assess systematic Reviews) will be conducted independently and in duplicate, with disagreements resolved by consensus. Evidence certainty statements for each review's conclusions (eg, Grading of Recommendations Assessment, Development and Evaluation (GRADE)) will be extracted or constructed de novo. A narrative synthesis will be conducted and delineated by the review question. Primary study overlap will be visualised using a citation matrix as well as calculated using the corrected covered area method.

ETHICS AND DISSEMINATION: No participant-identifying information will be used in this review. No ethics approval was required due to our study methodology. Our findings will be presented at national and international conferences and disseminated via social media and press releases. We will recruit at least one person living with cognitive impairment to collaborate on writing the plain language summary for the review.

PROSPERO REGISTRATION NUMBER: CRD42023412903.}, } @article {pmid38890022, year = {2024}, author = {Hammer, S and Schmidt, J and Conrad, A and Nos, C and Gellert, C and Ellert, C and Nuding, U and Pochaba, I}, title = {["The idea of rehabilitation will have to be completely rethought for this illness" - Qualitative results of an online survey on patients' experiences with inpatient rehabilitation for post COVID-19 condition (long COVID)].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {188}, number = {}, pages = {14-25}, doi = {10.1016/j.zefq.2024.05.007}, pmid = {38890022}, issn = {2212-0289}, mesh = {Humans ; *COVID-19/rehabilitation ; Germany ; Male ; Middle Aged ; Female ; Aged ; Adult ; Retrospective Studies ; Evidence-Based Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; Patient Satisfaction ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: In Germany, an estimated number of 70,000 people diagnosed with long COVID or post-COVID syndrome (PCS) had received inpatient medical rehabilitation by the end of 2022. Due to the heterogeneity of the clinical picture, the variability of interventions and inconsistent endpoints, previous studies on the effectiveness of rehabilitation are of limited value. It therefore remains unclear whether and to what extent rehabilitation measures established for, e.g., pulmonary, cardiovascular, or neurological diseases are suitable for patients with PCS.

OBJECTIVES: To identify the experiences and perspectives of those affected by PCS, in relation to inpatient rehabilitation and to describe patients' values and wishes with respect to evidence-based medicine.

METHODS: In January/February 2023, the German initiative "Long COVID Deutschland" conducted a retrospective online survey (39 closed items, two open answer fields) among adult PCS sufferers on their experiences with inpatient rehabilitation. Recruitment was carried out via social media and websites of patient initiatives. The open answers were analyzed using a structuring and summarizing qualitative content analysis according to Mayring, supplemented by descriptive representations of the distribution of standardized information.

RESULTS: Of 1,191 participants in the survey, 733 used open response formats to additionally explain their experiences and the effects of individual measures on their general condition. 366 (50%) reported that their state of health deteriorated, mainly because of strength or endurance training and too extensive treatment plans. The presence of a post-exertional malaise (PEM) or its insufficient consideration during rehabilitation was described as the main barrier. Recognition and acceptance of individual performance limits, flexible and coordinated individual treatment plans tailored to the patient's limitations, and support in coping with the disease were described as supportive factors. From the participants' perspective, learning strategies to avoid deterioration in their state of health due to overexertion, the so-called pacing, should be the core treatment goal for patients affected by PEM.

DISCUSSION: The results are not statistically representative but ensure systematic insights into the subjective perspectives of those affected, the consideration of which represents one of the three principles of evidence-based medicine. The results show that for PCS patients with PEM, even minimum requirements for rehabilitation measures can lead to overexertion and aggravation.

CONCLUSIONS: Common subject-specific rehabilitation concepts appear to be only partially suitable for dealing with the symptoms and the heterogeneity of the disease. Aims and interventions should be individually adapted, and the focus should be on pacing, disease coping and management. A reliable test for PEM and rehabilitation ability before the start of rehabilitation is needed to ensure safety for those affected. To adequately classify studies on the effectiveness of rehabilitation, risks and side effects should be disclosed.}, } @article {pmid38888186, year = {2024}, author = {Fontana, CE and Parreira, L and Pinheiro, S}, title = {Photobiomodulation in the Treatment of Dysgeusia in Patients with Long COVID: A Single-Blind, Randomized Controlled Trial.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {42}, number = {6}, pages = {438}, doi = {10.1089/pho.2024.0045}, pmid = {38888186}, issn = {2578-5478}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/complications ; *Dysgeusia/etiology ; *Low-Level Light Therapy ; SARS-CoV-2 ; Single-Blind Method ; Randomized Controlled Trials as Topic ; }, } @article {pmid38887284, year = {2024}, author = {Arron, HE and Marsh, BD and Kell, DB and Khan, MA and Jaeger, BR and Pretorius, E}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1386607}, pmid = {38887284}, issn = {1664-3224}, mesh = {*Fatigue Syndrome, Chronic/diagnosis/immunology/therapy/etiology ; Humans ; Neglected Diseases ; Dysbiosis ; Animals ; Gastrointestinal Microbiome/immunology ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available. Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease's multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. This comprehensive model not only advances our understanding of ME/CFS's pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease's complexity and the multifaceted approach required for its study and management.}, } @article {pmid38886814, year = {2024}, author = {Knowles, LM and Grewal, M and Drever, SA and Hoffman, JM and Friedly, JL and Herring, TE}, title = {A pilot randomized controlled trial of a telemedicine psychosocial intervention to improve symptom management in adults with long COVID: the COPE study protocol.}, journal = {Pilot and feasibility studies}, volume = {10}, number = {1}, pages = {93}, pmid = {38886814}, issn = {2055-5784}, support = {K23HD111628//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, abstract = {BACKGROUND: Long COVID is a serious public health concern due to its high prevalence and potentially debilitating symptoms. Symptoms may include fatigue, dyspnea, cognitive problems, insomnia, anxiety, and depression. There is currently no cure for long COVID, and the average length of recovery and proportion of patients who fully recover are still unknown. Subsequently, there is a critical need to improve function. Research in other chronic conditions suggests that psychosocial self-management interventions reduce symptom severity and interference with functioning. We describe the design of our study to examine the feasibility, acceptability, appropriateness, and preliminary efficacy of an intervention designed to improve symptom management and coping in adults with long COVID.

METHODS: This pilot trial (N = 50) uses a pragmatic, randomized two-group parallel design set within the University of Washington Post-COVID Rehabilitation and Recovery Clinic. The self-management intervention is a 6-week, group-based telemedicine intervention that teaches evidence-based strategies to manage common symptoms and improve stress management as well as communication and self-advocacy. The comparator is a wait-list control. Participants complete self-report measures of the primary and secondary outcomes at baseline and post-treatment/wait-list. Primary outcomes include intervention feasibility, acceptability, and appropriateness. Secondary outcomes include Patient-Reported Outcomes Measurement Information System measures of fatigue, sleep disturbance, cognitive difficulties, self-efficacy, pain interference, depression and anxiety symptoms, and a measure of long COVID symptoms and impression of change. At post-intervention, intervention participants also complete a qualitative interview to inform intervention refinement. Quantitative data will be examined using descriptive and statistical analysis including t-tests and chi-square tests to compare the intervention and wait-list groups on secondary outcomes. Qualitative data will be analyzed using the rigorous and accelerated data reduction technique (RADaR).

DISCUSSION: Results of this pilot randomized controlled trial will characterize the feasibility, acceptability, and appropriateness of the self-management intervention and inform intervention refinement necessary prior to further testing. Long COVID is a public health concern, and rehabilitation approaches that equip patients to manage symptoms may improve patient function and quality of life and reduce burden on the health care system.

TRIAL REGISTRATION: NCT05658536. December 16, 2022.}, } @article {pmid38884994, year = {2024}, author = {Oelsner, EC and Sun, Y and Balte, PP and Allen, NB and Andrews, H and Carson, A and Cole, SA and Coresh, J and Couper, D and Cushman, M and Daviglus, M and Demmer, RT and Elkind, MSV and Gallo, LC and Gutierrez, JD and Howard, VJ and Isasi, CR and Judd, SE and Kanaya, AM and Kandula, NR and Kaplan, RC and Kinney, GL and Kucharska-Newton, AM and Lackland, DT and Lee, JS and Make, BJ and Min, YI and Murabito, JM and Norwood, AF and Ortega, VE and Pettee Gabriel, K and Psaty, BM and Regan, EA and Sotres-Alvarez, D and Schwartz, D and Shikany, JM and Thyagarajan, B and Tracy, RP and Umans, JG and Vasan, RS and Wenzel, SE and Woodruff, PG and Xanthakis, V and Zhang, Y and Post, WS}, title = {Epidemiologic Features of Recovery From SARS-CoV-2 Infection.}, journal = {JAMA network open}, volume = {7}, number = {6}, pages = {e2417440}, pmid = {38884994}, issn = {2574-3805}, support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; R01 HL093009/HL/NHLBI NIH HHS/United States ; R21 HL165405/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; *SARS-CoV-2 ; Prospective Studies ; Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Pandemics ; United States/epidemiology ; }, abstract = {IMPORTANCE: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.

OBJECTIVE: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.

For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.

EXPOSURE: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.

MAIN OUTCOMES AND MEASURES: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.

RESULTS: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.

CONCLUSIONS AND RELEVANCE: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.}, } @article {pmid38883877, year = {2024}, author = {Kennedy, AB and Mitcham, A and Parris, K and Albertson, F and Sanchez Ferrer, L and O'Boyle, C and Patel, MK and Gartner, T and Broomer, AM and Katzman, E and Coffin, J and Grier, JT and Natafgi, N}, title = {Wonderings to research questions: Engaging patients in long COVID research prioritization within a learning health system.}, journal = {Learning health systems}, volume = {8}, number = {Suppl 1}, pages = {e10410}, pmid = {38883877}, issn = {2379-6146}, abstract = {BACKGROUND: An integral component of research within a learning health system is patient engagement at all stages of the research process. While there are well-defined best practices for engaging with patients on predetermined research questions, there is little specific methodology for engaging patients at the stage of research question formation and prioritization. Further, with an emerging disease such as Long COVID, population-specific strategies for meaningful engagement have not been characterized.

METHODS: The COVID-19 Focused Virtual Patient Engagement Studio (CoVIP studio) was a virtual panel created to facilitate patient-centered studies surrounding the effects of long-term COVID ("Long COVID") also known as post-acute SARS-CoV-2 syndrome (PASC). A diverse group of panelists was recruited and trained in several different areas of knowledge, competencies, and abilities regarding research and Long COVID. A three-step approach was developed that consisted of recording panelists' broad wonderings to generate patient-specific research questions.

RESULTS: The "wonderings" discussed in panelists' training sessions were analyzed to identify specific populations, interventions, comparators, outcomes, and timeframes (PICOT) elements, which were then used to create a survey to identify the elements of greatest importance to the panel. Based on the findings, 10 research questions were formulated using the PICOT format. The panelists then ranked the questions on perceived order of importance and distributed one million fictional grant dollars between the five chosen questions in the second survey. Through this stepwise prioritization process, the project team successfully translated panelists' research wonderings into investigable research questions.

CONCLUSION: This methodology has implications for the advancement of patient-engaged prioritization both within the scope of Long COVID research and in research on other rare or emerging diseases.}, } @article {pmid38883639, year = {2024}, author = {Omori, T and Hanafusa, M and Kondo, N and Miyazaki, Y and Okada, S and Fujiwara, T and Kuramochi, J}, title = {Specific sequelae symptoms of COVID-19 of Omicron variant in comparison with non-COVID-19 patients: a retrospective cohort study in Japan.}, journal = {Journal of thoracic disease}, volume = {16}, number = {5}, pages = {3170-3180}, pmid = {38883639}, issn = {2072-1439}, abstract = {BACKGROUND: The specific long-term sequela of coronavirus disease 2019 (COVID-19), also known as long COVID of the Omicron variant remain unclear, due to a lack of cohort studies that include non-COVID patients with cold-like symptoms. The study was conducted to examine specific sequelae symptoms after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which is considered the Omicron variant, compared with patients who were never-infected.

METHODS: In this retrospective cohort study, we sent questionnaires in November 2022, targeting those who visited our fever outpatient unit of a single institution from July to September 2022. SARS-CoV-2 infection status was determined by SARS-CoV-2 polymerase chain reaction (PCR) test results during the study period collected in electronic medical records. Clinical characteristics at 30 days or more since the date of SARS-CoV-2 PCR test were assessed by the questionnaires. Multiple logistic regression was performed to investigate the independent association between SARS-CoV-2 infection and possible sequelae symptoms.

RESULTS: In total, valid responses were received from 4,779 patients (mean age: 41.4 years, standard deviation: 19.8 years old). Among them, 3,326 (69.6%) and 1,453 (30.4%) were SARS-CoV-2 PCR test positive and never-infected, respectively. We found that patients with SARS-CoV-2 infection were more likely to have a loss of taste or smell [odds ratio (OR) 4.55, 95% confidence interval (CI): 1.93, 10.71], hair loss (OR 3.19, 95% CI: 1.67, 6.09), neurocognitive symptoms (OR 1.95, 95% CI: 1.43, 2.65), and respiratory symptoms (OR 1.23, 95% CI: 1.03, 1.47) than never-infected patients. SARS-CoV-2 infection was not associated with common cold symptoms, chronic physical distress, or diarrhea as sequelae symptoms. Further, SARS-CoV-2 vaccination showed protective effects on sequelae of loss of taste or smell and hair loss.

CONCLUSIONS: Loss of taste or smell, hair loss, neurocognitive symptoms, and respiratory symptoms were found to be specific sequelae of the SARS-CoV-2 Omicron variant. It is important not to miss these symptoms that follow SARS-CoV-2 infection and to recognize and manage the long COVID.}, } @article {pmid38881905, year = {2024}, author = {Landolina, N and Ricci, B and Veneziani, I and Alicata, C and Mariotti, FR and Pelosi, A and Quatrini, L and Mortari, EP and Carsetti, R and Vacca, P and Tumino, N and Azzarone, B and Moretta, L and Maggi, E}, title = {TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1368946}, pmid = {38881905}, issn = {1664-3224}, mesh = {Humans ; Angiotensin-Converting Enzyme 2/genetics/immunology ; *COVID-19/immunology/virology ; Cytokines/immunology ; *Killer Cells, Natural/immunology ; Lymphocyte Activation/immunology ; *SARS-CoV-2/immunology ; *Spike Glycoprotein, Coronavirus/immunology ; *Toll-Like Receptor 2/immunology ; *Toll-Like Receptor 4/immunology ; }, abstract = {BACKGROUND: In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated or exhausted. The aim of this paper was to establish whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger NK cells and through which receptor(s).

METHODS: SP-stimulated human NK cells have been evaluated for the expression of activation markers, cytokine release, and cytotoxic activity, as well as for gene expression profiles and NF-kB phosphorylation, and they have been silenced with specific small interfering RNAs.

RESULTS: SPs from the Wuhan strain and other variants of concern (VOCs) directly bind and stimulate purified NK cells by increasing activation marker expression, cytokine release, and cytolytic activity, prevalently in the CD56[bright]NK cell subset. VOC-SPs differ in their ability to activate NK cells, G614, and Delta-Plus strains providing the strongest activity in the majority of donors. While VOC-SPs do not trigger ACE2, which is not expressed on NK cells, or other activating receptors, they directly and variably bind to both Toll-like receptor 2 (TLR2) and TLR4. Moreover, SP-driven NK cell functions are inhibited upon masking such receptors or silencing the relative genes. Lastly, VOC-SPs upregulate CD56[dim]NK cell functions in COVID-19 recovered, but not in non-infected, individuals.

CONCLUSIONS: TLR2 and TLR4 are novel activating receptors for SP in NK cells, suggesting a new role of these cells in orchestrating the pathophysiology of SARS-CoV-2 infection. The pathogenic relevance of this finding is highlighted by the fact that free SP providing NK cell activation is frequently detected in a SARS-CoV-2 inflamed environment and in plasma of infected and long-COVID-19 subjects.}, } @article {pmid38881733, year = {2024}, author = {Tyrkalska, SD and Pérez-Sanz, F and Franco-Martínez, L and Rubio, CP and Tvarijonaviciute, A and Martínez-Subiela, S and Méndez-Hernández, M and González-Aumatell, A and Carreras-Abad, C and Domènech-Marçal, È and Cerón, JJ and Cayuela, ML and Mulero, V and Candel, S}, title = {Salivary biomarkers as pioneering indicators for diagnosis and severity stratification of pediatric long COVID.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1396263}, pmid = {38881733}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/diagnosis ; *Saliva/chemistry/virology ; *Biomarkers/analysis ; Child ; Female ; Male ; *SARS-CoV-2/isolation & purification ; *Severity of Illness Index ; Child, Preschool ; Adolescent ; }, abstract = {INTRODUCTION: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection. This disease is especially worrying in children since it can seriously alter their development. Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms post-acute infection.

METHODS: We measured the levels of 13 biomarkers in 105 saliva samples (49 from children with long COVID and 56 controls), and the Pearson correlation coefficient was used to analyse the correlations between the levels of the different salivary biomarkers. Multivariate logistic regression analyses were performed to determine which of the 13 analysed salivary biomarkers were useful to discriminate between children with long COVID and controls, as well as between children with mild and severe long COVID symptoms.

RESULTS: Pediatric long COVID exhibited increased oxidant biomarkers and decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms.

DISCUSSION: This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unravelling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals.}, } @article {pmid38881657, year = {2024}, author = {Li, Y and Han, M and Li, X}, title = {Clinical and prognostic implications of hyaluronic acid in patients with COVID-19 reinfection and first infection.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1406581}, pmid = {38881657}, issn = {1664-302X}, abstract = {OBJECTIVE: Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear.

METHODS: Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed.

RESULTS: The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05).

CONCLUSION: Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.}, } @article {pmid38881555, year = {2024}, author = {Whyler, N and Atkins, L and Hogg, P and Leong, A and Metcalfe, J and Scoullar, M and Tippett, E}, title = {Harnessing the Benefits of Telehealth in Long COVID Service Provision.}, journal = {Public health reviews}, volume = {45}, number = {}, pages = {1606948}, pmid = {38881555}, issn = {0301-0422}, } @article {pmid38881113, year = {2024}, author = {Muley, A and Mitra, S and Bhaliya, B and Soni, S and Joshi, A}, title = {A Systematic Review and Meta-analysis to Identify Risk Factors for Developing Long COVID-19.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {5}, pages = {68-74}, doi = {10.59556/japi.72.0528}, pmid = {38881113}, issn = {0004-5772}, mesh = {Humans ; *COVID-19/epidemiology ; Risk Factors ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Sex Factors ; }, abstract = {AIM: This systematic review and meta-analysis was undertaken to identify the risk factors of long coronavirus disease 2019 (COVID-19) to provide insight for selecting cases for more aggressive monitoring and treatment after COVID-19 infection and reduce morbidity due to long COVID-19.

MATERIALS AND METHODS: All relevant studies published till July 2022 were searched for in PubMed, Trip database, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library). Reference lists of the studies selected for appraisal were also considered. The National Institute of Health Clinical Database and Google Scholar were searched for unpublished studies. All cohort studies which studied risk factors for long COVID-19 in adults (>18 years age-group) were included. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction and bias assessment were. The outcomes were risk factors identified as being related with persistent symptoms 3 months after recovery from COVID-19. Random-effects model (RevMan 5.3) was used to pool the data.

RESULTS: Total nine studies were included with overall quality scores ranging from 16 to 19 out of the maximum 22. Pooled results demonstrated statistically significant association of long COVID-19 with female gender [odds ratio (OR) -1.67; 95% confidence interval (CI) 1.33-2.09], need of hospitalization (OR -1.80; 95% CI 1.22-2.64), and hospital stay (OR 2.41; 95% CI 0.75-4.07).

CONCLUSION: Female gender, need for hospitalization and duration of hospitalization during acute COVID-19 infection are the risk factors for later development of long COVID-19. There should be specific guidelines for monitoring and treatment of this population after acute COVID-19 infection.}, } @article {pmid38880718, year = {2024}, author = {Goddard, K and Myers, A and Ipsen, C}, title = {The hidden crisis: Long COVID's association with housing stability and home accessibility among people with disabilities.}, journal = {Disability and health journal}, volume = {17}, number = {4}, pages = {101650}, doi = {10.1016/j.dhjo.2024.101650}, pmid = {38880718}, issn = {1876-7583}, mesh = {Humans ; *Disabled Persons/statistics & numerical data ; *Housing/statistics & numerical data ; *COVID-19/epidemiology ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; *Architectural Accessibility ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged ; }, abstract = {BACKGROUND: The COVID-19 pandemic has given rise to the emerging phenomenon known as Long COVID, characterized by persistent symptoms long after the acute infection has passed. However, the relationship of Long COVID on housing stability and home accessibility remains underexplored.

OBJECTIVE: This manuscript aims to comprehensively examine the association of Long COVID on housing stability and accessibility, identifying challenges faced by people with Long COVID and potential strategies to address them.

METHODS: The study employs a cross-sectional mixed-methods approach, combining quantitative and qualitative methods. It analyzes data from 1533 people with disabilities, 514 with Long COVID and 1019 without Long COVID, to compare demographics, housing stability, financial concerns, housing problems, and home accessibility. Qualitative analysis extracts thematic insights from 13 participant narratives.

RESULTS: Individuals with Long COVID exhibit significantly higher rates of housing instability (21.1 % v. 8.1 %, p < 0.001) and financial concerns, such as worries about high rent or mortgage (50.4 % v. 40.0 %, p < 0.001), compared to those without Long COVID. They also report more frequent issues with pests (30.0 % v. 23.5 %, p < 0.01) and mold (22.0 % v. 12.7 %, p < 0.001) in their homes. Qualitative analysis reveals financial setbacks, difficulties in obtaining support, and the challenges of home accessibility.

CONCLUSIONS: Associations between Long COVID and challenges related to housing stability and home accessibility highlight the need for systemic changes, financial support, and advocacy. This research contributes to understanding Long COVID's challenges, informing policy development, and promoting compassionate responses, ensuring the well-being of people with Long COVID.}, } @article {pmid38880435, year = {2024}, author = {Caldas, B and Portela, M and Stelson, E and Singer, S and Amaral, T and Amaral, C and Escosteguy, C and Martins, M and de Andrade, CLT and Soares, L and Cornish, F and Rosenthal, M and Aveling, EL}, title = {Promoting equity, diversity, and inclusion in surveys: insights from a patient-engaged study to assess long COVID health-care needs in Brazil.}, journal = {Journal of clinical epidemiology}, volume = {173}, number = {}, pages = {111423}, doi = {10.1016/j.jclinepi.2024.111423}, pmid = {38880435}, issn = {1878-5921}, mesh = {Humans ; Brazil ; *COVID-19 ; Female ; Male ; Middle Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Health Services Accessibility/statistics & numerical data ; SARS-CoV-2 ; Patient Participation/statistics & numerical data ; Health Equity ; Longitudinal Studies ; Aged ; Health Services Needs and Demand ; Quality of Life ; Healthcare Disparities/statistics & numerical data ; Diversity, Equity, Inclusion ; }, abstract = {BACKGROUND AND OBJECTIVE: Long COVID (LC) refers to persistent symptoms after acute COVID-19 infection, which may persist for months or years. LC affects millions of people globally, with substantial impacts on quality of life, employment, and social participation. Ensuring access to effective, patient-centered care for LC demands evidence, grounded in inclusive representation of those affected by the condition. Yet survey studies frequently under-represent people with the most disabling disease presentations and racially and socioeconomically marginalized groups. We aimed to describe a patient-engaged approach to developing a survey to inform public LC health care and to assess its implementation in terms of enabling participation by diverse LC patients in Brazil.

METHODS: Survey development was iterative, achieved through an interdisciplinary collaboration among researchers including people living with LC, and grounded in 3 guiding principles: (1) evidence-based; (2) inclusive, intersectional, and patient-centered understanding of chronic illness and research participation; and (3) sensitivity to the context of health-care access.

RESULTS: The product of our collaboration was a longitudinal survey using a questionnaire assessing: LC symptoms; their clinical and functional evolution; and impacts on quality of life, household income, health service access, utilization, and out-of-pocket expenses. We illustrate how we operationalized our 3 principles through survey content, instrument design, and administration. Six hundred fifty-one participants with diverse LC symptoms, demography, and socioeconomic status completed the survey. We successfully included participants experiencing disabling symptoms, Black and mixed race participants, and those with lower education and income.

CONCLUSION: By centering patient experience, our novel, principles-based approach succeeded in promoting equity, diversity, and inclusion in LC survey research. These principles guiding patient-engaged collaboration have broad transferability. We encourage survey researchers working on chronic illness and in other contexts of marginalization and inequality to adopt them.}, } @article {pmid38879786, year = {2024}, author = {Faux-Nightingale, A and Somayajula, G and Bradbury, C and Bray, L and Burton, C and Chew-Graham, CA and Gardner, A and Griffin, A and Twohig, H and Welsh, V}, title = {Coproducing Health Information Materials With Young People: Reflections and Lessons Learned.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {3}, pages = {e14115}, pmid = {38879786}, issn = {1369-7625}, support = {686//National Institute of Health and Social Care Research, School of Primary Care Research/ ; }, mesh = {Humans ; *COVID-19 ; Adolescent ; Child ; Female ; Male ; Social Media ; Consumer Health Information ; SARS-CoV-2 ; }, abstract = {BACKGROUND: This paper describes and critically reflects on how children and young people (CYP) acted as public advisors to coproduce health information materials about Long Covid for younger audiences. This work was underpinned by the Lundy model, a framework which provides guidance on facilitating CYP to actively contribute to matters which affect them.

METHODS: Coproduction activity sessions took place with CYP in schools as well as video conferences with a CYP stakeholder group and CYP with Long Covid. Activities encouraged CYP to focus on the content, format, and design of materials and used problem-based and collaborative learning to encourage engagement with the project. Using a range of methods and open discussion, CYP codesigned a series of Long Covid health information materials for younger audiences.

RESULTS: Sixty-six CYP (aged 10-18), and two young adults were involved. CYP codesigned specifications for the final materials and provided feedback on early designs. The project led to the development of a series of health information materials targeted at CYP: a short social media campaign with six short videos and a 12-page illustrated leaflet about Long Covid; released on social media and distributed in local area. All the CYP were positive about the project and their involvement.

DISCUSSION: Involving CYP led to the development of innovative and engaging information materials (influence). Developing rapport was important when working with CYP and this was facilitated by using approaches and activities to establish an environment (space) where the CYP felt comfortable sharing their views (voice) and being listened to (audience) by the adults in the project. Working with external groups who are willing to share their expertise can help the meaningful involvement of voices 'less heard'.

PUBLIC CONTRIBUTION: One CYP coapplicant contributed to the project design and facilitation of PPIE sessions, 64 CYP were involved in the PPIE sessions to design and feedback on materials. Two young adult media producers worked with CYP to produce these materials, another CYP supported this process. Three public contributors were involved in the preparation of this manuscript.}, } @article {pmid38879571, year = {2024}, author = {Radtke, T and Künzi, L and Kopp, J and Rasi, M and Braun, J and Zens, KD and Winter, B and Anagnostopoulos, A and Puhan, MA and Fehr, JS}, title = {Effects of Pycnogenol® in people with post-COVID-19 condition (PYCNOVID): study protocol for a single-center, placebo controlled, quadruple-blind, randomized trial.}, journal = {Trials}, volume = {25}, number = {1}, pages = {385}, pmid = {38879571}, issn = {1745-6215}, mesh = {Humans ; *Plant Extracts/therapeutic use/adverse effects ; *Flavonoids/therapeutic use ; Randomized Controlled Trials as Topic ; Quality of Life ; COVID-19 ; Treatment Outcome ; SARS-CoV-2/drug effects ; Health Status ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Adult ; Female ; Male ; Antioxidants/therapeutic use/adverse effects ; Anti-Inflammatory Agents/therapeutic use/adverse effects ; }, abstract = {BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC.

METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study.

DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC.

TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.}, } @article {pmid38874912, year = {2024}, author = {Harris, E}, title = {Review Calls for Standardized Long COVID Definition.}, journal = {JAMA}, volume = {332}, number = {2}, pages = {97}, doi = {10.1001/jama.2024.10343}, pmid = {38874912}, issn = {1538-3598}, mesh = {Humans ; *COVID-19 ; *Post-Acute COVID-19 Syndrome/diagnosis ; SARS-CoV-2 ; *Terminology as Topic ; United States ; }, } @article {pmid38874693, year = {2024}, author = {Russell, SJ and Parker, K and Lehoczki, A and Lieberman, D and Partha, IS and Scott, SJ and Phillips, LR and Fain, MJ and Nikolich, JŽ}, title = {Post-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults.}, journal = {GeroScience}, volume = {46}, number = {6}, pages = {6563-6581}, pmid = {38874693}, issn = {2509-2723}, support = {R25AG076387/AG/NIA NIH HHS/United States ; R37AG020719/AG/NIA NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; R25 AG076387/AG/NIA NIH HHS/United States ; OT2HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; *Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; Aging/physiology ; }, abstract = {Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people worldwide. Many aspects of this condition are incompletely understood. Among them is how this condition may manifest itself in older adults and how it might impact the older population. Here, we briefly review the current understanding of PASC in the adult population and examine what is known on its features with aging. Finally, we outline the major gaps and areas for research most germane to older adults.}, } @article {pmid38874226, year = {2024}, author = {Kim, H and Kyung, S and Park, J and Lee, H and Lee, M and Smith, L and Rahmati, M and Shin, JY and Kang, J and Jacob, L and Papadopoulos, NG and Rhee, SY and Lee, J and Kim, HJ and Lee, H and Yon, DK}, title = {Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.}, journal = {Journal of medical virology}, volume = {96}, number = {6}, pages = {e29740}, doi = {10.1002/jmv.29740}, pmid = {38874226}, issn = {1096-9071}, support = {//National Research Foundation/ ; }, mesh = {Humans ; *COVID-19/epidemiology/immunology ; Middle Aged ; Male ; Female ; Republic of Korea/epidemiology ; United Kingdom/epidemiology ; Japan/epidemiology ; Adult ; Aged ; Cohort Studies ; SARS-CoV-2/immunology ; COVID-19 Vaccines/adverse effects/immunology ; Risk Factors ; Proportional Hazards Models ; Young Adult ; Skin Diseases/epidemiology ; }, abstract = {Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.}, } @article {pmid38873510, year = {2024}, author = {Rodrigues, AN and Paranhos, ACM and da Silva, LCM and Xavier, SS and Silva, CC and da Silva, R and de Vasconcelos, LA and Peixoto, IVP and Panzetti, TMN and Tavares, PR and Reis, CS and Launé, BF and Palácios, VRDCM and Vasconcelos, PFDC and Quaresma, JAS and Falcão, LFM}, title = {Effect of long COVID-19 syndrome on health-related quality of life: a cross-sectional study.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1394068}, pmid = {38873510}, issn = {1664-1078}, abstract = {PURPOSE: This study aimed to assess the association of anxiety, headache, and insomnia on the QoL of patients with long COVID-19.

METHODS: We conducted a cross-sectional survey between August 2020 and March 2023. A total of 200 participants were eligible, 53 were excluded and 147 patients with long COVID were included. QoL was evaluated across eight domains using the 36-Item Short Form Health Survey (SF-36). Standardized protocols including the Beck Anxiety Inventory (BAI) (n = 103), Pittsburgh Sleep Quality Index (PSQI) (n = 73), and Migraine Disability Assessment (MIDAS) (n = 67) were also used.

RESULTS: Participants with sleep disorders had significantly lower Vitality (p < 0.001). Participants with anxiety disorders had significantly lower Vitality (p = 0.001), poorer Mental Health (p = 0.008), and more severe Bodily Pain (p = 0.008). Participants with headache had significantly lower Vitality (p = 0.032), poorer Mental Health (p = 0.036), and poorer Physical Functioning (p = 0.016). Participants with both headache and anxiety had significantly lower Vitality (p = 0.005) and Mental Health (p = 0.043) domain scores. Correlation analysis revealed that higher scores for anxiety, sleep disorder, and headache were independently correlated with poorer QoL across various domains. The presence of sleep disorder was associated with a fourfold increase in risk of experiencing diminished Vitality (odds ratio [OR]4.47; 95% CI 1.01-19.69; p = 0.048).

CONCLUSION: Participants with anxiety, sleep, and headache disorders tended to have a worse QoL. The Vitality and Mental Health domains were the most adversely affected in patients with long COVID. Sleep disorders were associated with a fourfold increase in the risk of poor Vitality.}, } @article {pmid38873310, year = {2024}, author = {Fisher, KA and Mazor, KM and Epstein, MM and Goldthwait, L and Abu Ghazaleh, H and Zhou, Y and Crawford, S and Marathe, J and Linas, BP}, title = {Long COVID awareness and receipt of medical care: a survey among populations at risk for disparities.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1360341}, pmid = {38873310}, issn = {2296-2565}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *COVID-19/epidemiology ; Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; *Healthcare Disparities/statistics & numerical data ; Hispanic or Latino/statistics & numerical data ; SARS-CoV-2 ; Surveys and Questionnaires ; United States ; Black or African American ; White ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has been characterized by disparities in disease burden and medical care provision. Whether these disparities extend to long COVID awareness and receipt of medical care is unknown. We aimed to characterize awareness of long COVID and receipt of medical care for long COVID symptoms among populations who experience disparities in the United States (US).

METHODS: We conducted a cross-sectional survey among a national sample of US adults between January 26-February 5, 2023. We surveyed approximately 2,800 adults drawn from the Ipsos probability-based KnowledgePanel® who identify as White, Black, or Hispanic, with over-sampling of Black, Hispanic, and Spanish-proficient adults. Awareness of long COVID was assessed with the question, "Have you heard of long COVID? This is also referred to as post-COVID, Long-haul COVID, Post-acute COVID-19, or Chronic COVID." Respondents reporting COVID-19 symptoms lasting longer than 1 month were classified as having long COVID and asked about receipt of medical care.

RESULTS: Of the 2,828 respondents, the mean age was 50.4 years, 52.8% were female, 40.2% identified as Hispanic, 29.8% as Black, and 26.7% as White. 18% completed the survey in Spanish. Overall, 62.5% had heard of long COVID. On multivariate analysis, long COVID awareness was lower among respondents who identified as Black (OR 0.64; 95% CI 0.51, 0.81), Hispanic and completed the survey in English (OR 0.59; 95% CI 0.46, 0.76), and Hispanic and completed the survey in Spanish (OR 0.31, 95% C.I. 0.23, 0.41), compared to White respondents (overall p < 0.001). Long COVID awareness was also associated with educational attainment, higher income, having health insurance, prior history of COVID-19 infection, and COVID-19 vaccination. Among those reporting symptoms consistent with long COVID (n = 272), 26.8% received medical care. Older age, longer symptom duration and greater symptom impact were associated with receipt of medical care for long COVID symptoms. Of those who received care, most (77.8%) rated it as less than excellent on a 5-point scale.

DISCUSSION: This survey reveals limited awareness of long COVID and marked disparities in awareness according to race, ethnicity, and language. Targeted public health campaigns are needed to raise awareness.}, } @article {pmid38873142, year = {2024}, author = {Li, Z and Xia, Q and Feng, J and Chen, X and Wang, Y and Ren, X and Wu, S and Yang, R and Li, J and Liu, Y and Lu, Y and Chen, J}, title = {The causal role of gut microbiota in susceptibility of Long COVID: a Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1404673}, pmid = {38873142}, issn = {1664-302X}, abstract = {BACKGROUND: Long COVID is a major challenge facing the public. Gut microbiota is closely related to Long COVID. However, the causal effects between gut microbiota and Long COVID remains unclear.

METHODS: Using summary statistics from Genome-Wide Association Studies (GWAS), Mendelian randomization (MR) analyses were performed to investigate the relationship between gut microbiota and Long COVID. The primary statistical method employed was Inverse Variance Weighted (IVW). Sensitivity analyses were then conducted to evaluate the reliability of the findings and account for potential confounding variables. Finally, a reverse MR analysis was conducted to examine potential associations between Long COVID and genetically predicted gut microbiota compositions.

RESULTS: There were 2 positive and 1 negative causal effect between gut microbiota and Long COVID. Meta-analysis results show that genus Parasutterella (OR = 1.145, 95%CI = 1.035 ∼ 1.266, P = 0.008) and genus Oscillospira (OR = 1.425, 95%CI = 1.235 ∼ 1.645, P < 0.001) significantly increased the risk of Long COVID. And genus Eisenbergiella (OR = 0.861, 95%CI = 0.785 ∼ 0.943, P = 0.001) significantly decreased the risk of Long COVID. Neither the pleiotropy nor the heterogeneity was observed. Reverse causal effect does not hold.

CONCLUSION: Our research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and Long COVID, supporting the role of the gut microbiota in Long COVID. It is possible that different taxa play a role in the development of Long COVID. The causal relationships identified in this study require further investigation.}, } @article {pmid38871876, year = {2024}, author = {Wong, C}, title = {What causes long COVID? Case builds for rogue antibodies.}, journal = {Nature}, volume = {630}, number = {8018}, pages = {798-799}, pmid = {38871876}, issn = {1476-4687}, mesh = {Humans ; *Antibodies, Viral/adverse effects/blood/immunology ; *Post-Acute COVID-19 Syndrome/blood/etiology/immunology/physiopathology ; SARS-CoV-2/immunology ; Animals ; Mice ; }, } @article {pmid38871773, year = {2024}, author = {van der Feltz-Cornelis, CM and Sweetman, J and Turk, F and Allsopp, G and Gabbay, M and Khunti, K and Williams, N and Montgomery, H and Heightman, M and Lip, GYH and Crooks, MG and Strain, WD and Loveless, A and Hishmeh, L and Smith, N and Banerjee, A}, title = {Integrated care policy recommendations for complex multisystem long term conditions and long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13634}, pmid = {38871773}, issn = {2045-2322}, support = {COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; COV-LT2-0043//National Institute of Health Research (NIHR)/ ; }, mesh = {Humans ; *COVID-19/epidemiology/therapy ; *Delivery of Health Care, Integrated/organization & administration ; SARS-CoV-2/isolation & purification ; Male ; Female ; United Kingdom/epidemiology ; Health Policy ; Delphi Technique ; Consensus ; Middle Aged ; Adult ; Pandemics ; }, abstract = {The importance of integrated care for complex, multiple long term conditions was acknowledged before the COVID pandemic but remained a challenge. The pandemic and consequent development of Long COVID required rapid adaptation of health services to address the population's needs, requiring service redesigns including integrated care. This Delphi consensus study was conducted in the UK and found similar integrated care priorities for Long COVID and complex, multiple long term conditions, provided by 480 patients and health care providers, with an 80% consensus rate. The resultant recommendations were based on more than 1400 responses from survey participants and were supported by patients, health care professionals, and by patient charities. Participants identified the need to allocate resources to: support integrated care, provide access to care and treatments that work, provide diagnostic procedures that support the personalization of treatment in an integrated care environment, and enable structural consultation between primary and specialist care settings including physical and mental health care. Based on the findings we propose a model for delivering integrated care by a multidisciplinary team to people with complex multisystem conditions. These recommendations can inform improvements to integrated care for complex, multiple long term conditions and Long COVID at international level.}, } @article {pmid38871766, year = {2024}, author = {Meijsen, J and Hu, K and Krebs, MD and Athanasiadis, G and Washbrook, S and Zetterberg, R and Avelar E Silva, RN and Shorter, JR and Gådin, JR and Bergstedt, J and Howard, DM and Ye, W and Lu, Y and Valdimarsdóttir, UA and Ingason, A and Helenius, D and Plana-Ripoll, O and McGrath, JJ and Micali, N and Andreassen, OA and Werge, TM and Fang, F and Buil, A}, title = {Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5064}, pmid = {38871766}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 MH123724/MH/NIMH NIH HHS/United States ; U01 MH094432/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Comorbidity ; *Mental Disorders/genetics/epidemiology ; Male ; Denmark/epidemiology ; Sweden/epidemiology ; Female ; *Cardiovascular Diseases/genetics/epidemiology ; Autism Spectrum Disorder/genetics/epidemiology ; Metabolic Diseases/genetics/epidemiology ; Adult ; Gene-Environment Interaction ; Schizophrenia/genetics/epidemiology ; Middle Aged ; Attention Deficit Disorder with Hyperactivity/genetics/epidemiology ; Scandinavians and Nordic People ; }, abstract = {Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.}, } @article {pmid38870106, year = {2024}, author = {Morgenstern, C and Laydon, DJ and Whittaker, C and Mishra, S and Haw, D and Bhatt, S and Ferguson, NM}, title = {The interaction of disease transmission, mortality, and economic output over the first 2 years of the COVID-19 pandemic.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0301785}, pmid = {38870106}, issn = {1932-6203}, support = {MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/mortality/epidemiology/transmission/economics ; Humans ; *Gross Domestic Product ; Europe/epidemiology ; *Pandemics ; *Bayes Theorem ; *SARS-CoV-2 ; Travel ; }, abstract = {BACKGROUND: The COVID-19 pandemic has caused over 7.02 million deaths as of January 2024 and profoundly affected most countries' Gross Domestic Product (GDP). Here, we study the interaction of SARS-CoV-2 transmission, mortality, and economic output between January 2020 and December 2022 across 25 European countries.

METHODS: We use a Bayesian mixed effects model with auto-regressive terms to estimate the temporal relationships between disease transmission, excess deaths, changes in economic output, transit mobility and non-pharmaceutical interventions (NPIs) across countries.

RESULTS: Disease transmission intensity (logRt) decreases GDP and increases excess deaths, where the latter association is longer-lasting. Changes in GDP as well as prior week transmission intensity are both negatively associated with each other (-0.241, 95% CrI: -0.295 - -0.189). We find evidence of risk-averse behaviour, as changes in transit and prior week transmission intensity are negatively associated (-0.055, 95% CrI: -0.074 to -0.036). Our results highlight a complex cost-benefit trade-off from individual NPIs. For example, banning international travel is associated with both increases in GDP (0.014, 0.002-0.025) and decreases in excess deaths (-0.014, 95% CrI: -0.028 - -0.001). Country-specific random effects, such as the poverty rate, are positively associated with excess deaths while the UN government effectiveness index is negatively associated with excess deaths.

INTERPRETATION: The interplay between transmission intensity, excess deaths, population mobility and economic output is highly complex, and none of these factors can be considered in isolation. Our results reinforce the intuitive idea that significant economic activity arises from diverse person-to-person interactions. Our analysis quantifies and highlights that the impact of disease on a given country is complex and multifaceted. Long-term economic impairments are not fully captured by our model, as well as long-term disease effects (Long COVID).}, } @article {pmid38869167, year = {2025}, author = {Özçelik, N and Özyurt, S and Topaloğlu, EŞ and Gümüş, A and Hocaoğlu, Ç and Şahin, Ü}, title = {Long COVID: A risk factor for anxiety, depression, and suicidality?.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {73}, number = {1}, pages = {67-74}, doi = {10.1177/10815589241261291}, pmid = {38869167}, issn = {1708-8267}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Male ; *Depression/psychology ; *Anxiety/psychology ; Risk Factors ; *Suicidal Ideation ; Middle Aged ; Adult ; Cross-Sectional Studies ; SARS-CoV-2 ; Surveys and Questionnaires ; Aged ; }, abstract = {In many COVID-19 survivors, symptoms continue for a long time. This study aims to examine the relationship between the long-term effects of COVID-19, levels of anxiety and depression, and suicidal ideation with sociodemographic factors and symptoms. A cross-sectional study was conducted on patients who came for control at least 3 months after having COVID-19 disease, in the stable period, and still have symptoms after COVID-19. Demographic characteristics, symptoms, The Beck Depression Scale (BDS), The Beck Anxiety Scale (BAS), and suicidal ideation were assessed with face-to-face questionnaires. A total of 490 patients participated in the study. Thirty percent of patients scored positive on the BDS and 46% scored high on the BAS. Female sex was found to be a risk factor. Anxiety and depression were found to be significantly associated with long COVID symptoms. Both BAS and BDS scores were significantly higher in people with suicidality compared to others, and long-term symptoms were found to be statistically associated with this situation. Depression and anxiety are common in cases of long COVID. It is important for healthcare professionals to be aware of these potential mental health consequences, especially suicidality, and to provide appropriate support and interventions for individuals with long COVID.}, } @article {pmid38868283, year = {2024}, author = {Rathod, N and Kumar, S and Chavhan, R and Acharya, S and Rathod, S}, title = {Navigating the Long Haul: A Comprehensive Review of Long-COVID Sequelae, Patient Impact, Pathogenesis, and Management.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60176}, pmid = {38868283}, issn = {2168-8184}, abstract = {Long COVID, characterized by persistent symptoms following a SARS-CoV-2 infection, presents a significant public health challenge with wide-ranging implications. This comprehensive review explores the epidemiology, clinical manifestations, pathogenesis, risk factors, diagnosis, patient impact, management strategies, and long-term prognosis of COVID. Despite a varied symptomatology that spans multiple organ systems, including respiratory, neurological, and cardiovascular systems, this condition is primarily associated with chronic inflammation and potential viral persistence. Prevalence varies, influenced by the initial infection severity, demographic factors, and pre-existing conditions. The review emphasizes the necessity for healthcare systems to adapt to the needs of long-COVID patients by developing standardized diagnostic criteria and personalized, multidisciplinary treatment approaches. Current research gaps and future directions are identified, highlighting the urgent need for further studies on pathophysiological mechanisms and effective therapeutic interventions. This review aims to inform healthcare providers, researchers, and policymakers, enhancing patient care and guiding ongoing and future research initiatives. The continuing global focus and collaborative efforts offer hope for improved outcomes for those affected by long COVID, marking an essential step towards addressing this emergent condition comprehensively.}, } @article {pmid38868140, year = {2023}, author = {Otani, K and Yoshikawa, R and Naito, A and Fukushima, H and Matsuishi, K}, title = {Remorse-related suicide attempts among young mothers after COVID-19 infection.}, journal = {PCN reports : psychiatry and clinical neurosciences}, volume = {2}, number = {2}, pages = {e116}, pmid = {38868140}, issn = {2769-2558}, abstract = {BACKGROUND: In Japan, there is a tendency to view COVID-19 infection as one's own responsibility, which may result in more feelings of guilt than in other countries. During the COVID-19 pandemic, the curfew imposed by COVID-19 restricted social behavior and increased anxiety and loneliness, which may have increased the risk of suicide among young women, especially mothers who were highly stressed regarding COVID-19 infection in their children.

CASE PRESENTATION: This is a case report of two Japanese mothers who developed feelings of guilt following infection with COVID-19, leading to suicide attempts. They feared stigma or denial due to the infection, which they were unable to explain to others, leading to a heightened sense of self-blame and suicide attempts. In addition, Japanese women have a heavy burden of housework, despite their dual roles at home and at work; the pandemic's behavioral restrictions led to increased time at home and stress. These women were also more affected by the economic crisis in the early stages of the pandemic than men. Relatedly, neuropsychiatric symptoms that persisted after recovering from COVID-19, such as depression, anxiety, fatigue, and pain, namely postacute COVID-19 syndrome or long COVID, may have precipitated the suicidal ideation in these cases. Moreover, the complication of bipolar disorder by COVID-19 could have led to suicide attempts caused by infection-related neuropsychiatric symptoms and the exacerbation of the bipolar disorder by restrictions imposed during the pandemic.

CONCLUSION: Suicide prevention measures need to be taken more seriously among mothers during or after the COVID-19 pandemic.}, } @article {pmid38867247, year = {2024}, author = {Laestadius, LI and Guidry, JPD and Wahl, MM and Perrin, PB and Carlyle, KE and Dong, X and Gharbo, R and Campos-Castillo, C}, title = {"The dream is that there's one place you go": a qualitative study of women's experiences seeking care from Long COVID clinics in the USA.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {243}, pmid = {38867247}, issn = {1741-7015}, mesh = {Humans ; Female ; *COVID-19/psychology/epidemiology ; Middle Aged ; Adult ; *Qualitative Research ; United States ; *Patient Acceptance of Health Care/psychology ; Aged ; Health Services Accessibility ; SARS-CoV-2 ; Ambulatory Care Facilities ; Post-Acute COVID-19 Syndrome ; Interviews as Topic ; Young Adult ; }, abstract = {BACKGROUND: Seeking and obtaining effective health care for Long COVID remains a challenge in the USA. Women have particularly been impacted, as they are both at higher risk of developing Long COVID and of facing gendered barriers to having symptoms acknowledged. Long COVID clinics, which provide multidisciplinary and coordinated care, have emerged as a potential solution. To date, however, there has been little examination of U.S. patient experiences with Long COVID clinics and how patients may or may not have come to access care at a Long COVID clinic.

METHODS: We conducted semi-structured interviews with 30 U.S. women aged 18 or older who had experienced Long COVID symptoms for at least 3 months, who had not been hospitalized for acute COVID-19, and who had seen at least one medical provider about their symptoms. Participants were asked about experiences seeking medical care for Long COVID. Long COVID clinic-related responses were analyzed using qualitative framework analysis to identify key themes in experiences with Long COVID clinics.

RESULTS: Of the 30 women, 43.3% (n = 13) had been seen at a Long COVID clinic or by a provider affiliated with a Long COVID clinic and 30.0% (n = 9) had explored or attempted to see a Long COVID clinic but had not been seen at time of interview. Participants expressed five key themes concerning their experiences with seeking care from Long COVID clinics: (1) Access to clinics remains an issue, (2) Clinics are not a one stop shop, (3) Not all clinic providers have sufficient Long COVID knowledge, (4) Clinics can offer validation and care, and (5) Treatment options are critical and urgent.

CONCLUSIONS: While the potential for Long COVID clinics is significant, findings indicate that ongoing barriers to care and challenges related to quality and coordination of care hamper that potential and contribute to distress among women seeking Long COVID care. Since Long COVID clinics are uniquely positioned and framed as being the place to go to manage complex symptoms, it is critical to patient wellbeing that they be properly resourced to provide a level of care that complies with emerging best practices.}, } @article {pmid38866353, year = {2024}, author = {Fox, J and Verduzco-Gutierrez, M and Sanchez, S and Lopez, M and Ali, F and Quesada, O and Henry, TD and Shah, SA}, title = {Enhanced External Counterpulsation Improves Long COVID-Associated Symptoms.}, journal = {The American journal of cardiology}, volume = {224}, number = {}, pages = {12-13}, pmid = {38866353}, issn = {1879-1913}, support = {K23 HL151867/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Counterpulsation/methods ; Male ; *SARS-CoV-2 ; Female ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38865966, year = {2024}, author = {Hamlin, RE and Blish, CA}, title = {Challenges and opportunities in long COVID research.}, journal = {Immunity}, volume = {57}, number = {6}, pages = {1195-1214}, pmid = {38865966}, issn = {1097-4180}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; T32 AI007502/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Biomarkers ; Biomedical Research ; *COVID-19/immunology/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/physiology/immunology ; }, abstract = {Long COVID (LC) is a condition in which patients do not fully recover from the initial SARS-CoV-2 infection but rather have persistent or new symptoms for months to years following the infection. Ongoing research efforts are investigating the pathophysiologic mechanisms of LC and exploring preventative and therapeutic treatment approaches for patients. As a burgeoning area of investigation, LC research can be structured to be more inclusive, innovative, and effective. In this perspective, we highlight opportunities for patient engagement and diverse research expertise, as well as the challenges of developing definitions and reproducible studies. Our intention is to provide a foundation for collaboration and progress in understanding the biomarkers and mechanisms driving LC.}, } @article {pmid38865773, year = {2024}, author = {Kukreti, S and Yeh, CY and Chen, YJ and Lu, MT and Li, MC and Lai, YY and Li, CY and Ko, NY}, title = {Unveiling long COVID symptomatology, co-occurrence trends, and symptom distress post SARS-CoV-2 infection.}, journal = {Journal of infection and public health}, volume = {17}, number = {7}, pages = {102464}, doi = {10.1016/j.jiph.2024.05.052}, pmid = {38865773}, issn = {1876-035X}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; Taiwan/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Aged ; Latent Class Analysis ; Prevalence ; Psychological Distress ; Stress, Psychological/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Long COVID, an emerging public health issue, is characterized by persistent symptoms following SARS-CoV-2 infection. This study aims to explore the relationship between post-COVID-19 symptomatology and patient distress employing Latent Class Analysis to uncover symptom co-occurrence patterns and their association with distress.

METHODS: A cross-sectional study was conducted using an online survey among 240 participants from a university and affiliated hospital of southern Taiwan. The survey quantified distress due to persistent symptoms and assessed the prevalence of Long COVID, symptom co-occurrence, and latent symptom classes. Latent Class Analysis (LCA) identified distinct symptom patterns, and multiple regression models evaluated associations between symptom patterns, distress, and demographic factors.

RESULTS: The study found that 80 % of participants experienced Long COVID, with symptoms persisting for over three months. Individuals with multiple COVID-19 infections showed a significant increase in general (β = 1.79), cardiovascular (β = 0.61), and neuropsychological symptoms (β = 2.18), and higher total distress scores (β = 6.35). Three distinct symptomatology classes were identified: "Diverse", "Mild", and "Severe" symptomatology. The "Mild Symptomatology" class was associated with lower distress (-10.61), while the "Severe Symptomatology" class showed a significantly higher distress due to symptoms (13.32).

CONCLUSION: The study highlights the significant impact of Long COVID on individuals, with distinct patterns of symptomatology and associated distress. It emphasizes the cumulative effect of multiple COVID-19 infections on symptom severity and the importance of tailored care strategies.}, } @article {pmid38865213, year = {2024}, author = {Sharma, S and El-Alfi, V and Greene, D}, title = {Maintaining and Improving Virtual Call Centers for Public Health: The CUNY Recovery Corps Experience.}, journal = {Journal of public health management and practice : JPHMP}, volume = {30}, number = {6}, pages = {869-878}, doi = {10.1097/PHH.0000000000001959}, pmid = {38865213}, issn = {1550-5022}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; New York City ; *SARS-CoV-2 ; *Public Health/methods ; Pandemics/prevention & control ; }, abstract = {CONTEXT: In the early stages of the COVID-19 pandemic in New York City, individuals who tested positive, exposed contacts, and their families faced significant challenges in accessing essential resources for successful quarantine and isolation. These resources included alternative housing, food access, grocery delivery, missed wage assistance, transportation for household members, medical care, and more.

PROGRAM: The City University of New York (CUNY) Recovery Corps emerged as an innovative virtual resource navigation service to connect New Yorkers to essential resources and later to vaccinations, treatment, and services for Long COVID. The program prioritized reaching people living in underserved and under-resourced neighborhoods. Over 3 years, it made a substantial impact, reaching 374 728 New Yorkers and connecting 135 147 to crucial resources.

IMPLEMENTATION: Implementing a successful virtual navigation center amidst a global pandemic posed unique challenges. It required well-established systems to provide services, manage staff, build community, and both assure and improve service quality.

EVALUATION: Continuous quality assurance and process improvement efforts resulted in a nearly 10-point increase in successful client-resource connections program-wide, with individual navigators showing improvements of up to 20%. Staff-led initiatives, such as population-specific resource guides and incentive awards, boosted morale and cohesion. Providing continuous professional development opportunities and requested training including trauma-informed care, self-care, and strategies for managing grief contributed to staff retention and improved client interactions.

DISCUSSION: The CUNY Recovery Corps provides a blueprint for setting up navigation services for emergency response and supporting health and social services. The current paper delves into the intensive quality improvement efforts, program management infrastructure, and staff support that made this program a success. By applying these lessons on establishing and maintaining a virtual call center prioritizing the client's well-being and staff strengths, policymakers and social service leaders can effectively address various health and social service needs proactively rather than rebuilding after each disaster.}, } @article {pmid38865058, year = {2024}, author = {Pajuelo, D and Dezortova, M and Hajek, M and Ibrahimova, M and Ibrahim, I}, title = {Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients.}, journal = {Magma (New York, N.Y.)}, volume = {37}, number = {5}, pages = {937-946}, pmid = {38865058}, issn = {1352-8661}, support = {NU22-A-124//Ministerstvo Zdravotnictví Ceské Republiky/ ; IKEM//Ministerstvo Zdravotnictví Ceské Republiky/ ; IN 00023001//Ministerstvo Zdravotnictví Ceské Republiky/ ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/metabolism ; *Corpus Callosum/diagnostic imaging/metabolism ; Male ; Female ; Middle Aged ; Adult ; *Choline/metabolism ; *Aspartic Acid/analogs & derivatives/metabolism ; *Creatine/metabolism ; *SARS-CoV-2 ; Aged ; *Proton Magnetic Resonance Spectroscopy/methods ; Inositol/metabolism ; Case-Control Studies ; Magnetic Resonance Spectroscopy/methods ; }, abstract = {OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID.

MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies.

RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91).

DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.}, } @article {pmid38864760, year = {2024}, author = {Hunt, K and Maclean, A and Locock, L and O'Dwyer, C and Nettleton, S and Ziebland, S and Wild, C}, title = {Young adults' experiences of biographical retrogression whilst living with long COVID.}, journal = {Sociology of health & illness}, volume = {46}, number = {8}, pages = {1526-1546}, doi = {10.1111/1467-9566.13798}, pmid = {38864760}, issn = {1467-9566}, support = {COV/LTE/20/04/CSO_/Chief Scientist Office/United Kingdom ; COV-LT2-0005//National Institute for Health Research/ ; //Girdlers' New Zealand Health Research Council Fellowship/ ; COV/LTE/04/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; *COVID-19/psychology ; Male ; Female ; United Kingdom ; Adult ; Young Adult ; *SARS-CoV-2 ; Interviews as Topic ; Narration ; Qualitative Research ; Adaptation, Psychological ; }, abstract = {During the early years (2020-2021) of the COVID-19 pandemic, relatively little attention focused on experiences of people with long-lasting symptoms, particularly young adults who were commonly understood to be invulnerable to serious effects of the virus. Drawing on narrative interviews with 15 adults in their twenties and living in the UK when they became ill with long COVID, we explore contextual factors which made their long COVID illness experience, and the wholescale disruption to their lives, challenging. We propose that existing adaptations of the concept of biographical disruption are problematic for this group, and instead suggest that 'biographical retrogression' may more accurately reflect these young adults' experiences. For many of these young adults, their illness occurred at a crucial stage in forming or solidifying (presumed) adult trajectories. Secondly, the recency of long COVID did not allow for comparison with an existing 'grand narrative' of recovery, so the future course of their illness was not just unknown for them as individuals; there was no prognostic map against which to assess their symptoms. Thirdly, the lives of people with long COVID have been disrupted in the context of global societal disruption by the same virus, rendering their experiences both topical yet invisible.}, } @article {pmid38863829, year = {2024}, author = {Raj, ST and Bruce, AW and Anbalagan, M and Srinivasan, H and Chinnappan, S and Rajagopal, M and Khanna, K and Chandramoorthy, HC and Mani, RR}, title = {COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1384939}, pmid = {38863829}, issn = {2235-2988}, mesh = {*COVID-19/immunology/complications/therapy ; Humans ; *Dysbiosis ; *Gastrointestinal Microbiome ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; Gastrointestinal Tract/microbiology ; COVID-19 Drug Treatment ; }, abstract = {The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.}, } @article {pmid38863076, year = {2024}, author = {Thankachen, SS and Devasenapathy, N and Bassi, A and Ghosh, A and Arfin, S and Gummidi, B and Basheer, A and Bangi, A and Sahu, D and Bhalla, A and Blesson, M and Jain, M and Jha, V}, title = {Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.}, journal = {Trials}, volume = {25}, number = {1}, pages = {378}, pmid = {38863076}, issn = {1745-6215}, support = {ECD/CSTPU/Adhoc/COVID-19/13/2021-22//Indian Council of Medical Research/ ; }, mesh = {Humans ; *Colchicine/therapeutic use/adverse effects ; Double-Blind Method ; *COVID-19/complications ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anti-Inflammatory Agents/therapeutic use/adverse effects ; Inflammation/drug therapy ; Cardiovascular Diseases/prevention & control ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Adult ; }, abstract = {BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID.

METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared.

DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice.

TRIAL REGISTRATION: This clinical trial has been registered prospectively on www.

CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.}, } @article {pmid38862978, year = {2024}, author = {Honein-AbouHaidar, G and Rizkallah, C and Bou Akl, I and Morgano, GP and Vrbová, T and van Deventer, E and Del Rosario Perez, M and Akl, EA}, title = {Understanding contextual and practical factors to inform WHO recommendations on using chest imaging to monitor COVID-19 pulmonary sequelae: a qualitative study exploring stakeholders' perspective.}, journal = {Health research policy and systems}, volume = {22}, number = {1}, pages = {67}, pmid = {38862978}, issn = {1478-4505}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *COVID-19 ; *Qualitative Research ; Male ; *World Health Organization ; Female ; *SARS-CoV-2 ; Adult ; Middle Aged ; Stakeholder Participation ; Aged ; Lung/diagnostic imaging ; Health Personnel ; }, abstract = {BACKGROUND: A recommendation by the World Health Organization (WHO) was issued about the use of chest imaging to monitor pulmonary sequelae following recovery from COVID-19. This qualitative study aimed to explore the perspective of key stakeholders to understand their valuation of the outcome of the proposition, preferences for the modalities of chest imaging, acceptability, feasibility, impact on equity and practical considerations influencing the implementation of using chest imaging.

METHODS: A qualitative descriptive design using in-depth interviews approach. Key stakeholders included adult patients who recovered from the acute illness of COVID-19, and providers caring for those patients. The Evidence to Decision (EtD) conceptual framework was used to guide data collection of contextual and practical factors related to monitoring using imaging. Data analysis was based on the framework thematic analysis approach.

RESULTS: 33 respondents, including providers and patients, were recruited from 15 different countries. Participants highly valued the ability to monitor progression and resolution of long-term sequelae but recommended the avoidance of overuse of imaging. Their preferences for the imaging modalities were recorded along with pros and cons. Equity concerns were reported across countries (e.g., access to resources) and within countries (e.g., disadvantaged groups lacked access to insurance). Both providers and patients accepted the use of imaging, some patients were concerned about affordability of the test. Facilitators included post- recovery units and protocols. Barriers to feasibility included low number of specialists in some countries, access to imaging tests among elderly living in nursing homes, experience of poor coordination of care, emotional exhaustion, and transportation challenges driving to a monitoring site.

CONCLUSION: We were able to demonstrate that there is a high value and acceptability using imaging but there were factors influencing feasibility, equity and some practical considerations associated with implementation. We had a few suggestions to be considered by the expert panel in the formulation of the guideline to facilitate its implementation such as using validated risk score predictive tools for lung complications to recommend the appropriate imaging modality and complementary pulmonary function test.}, } @article {pmid38862619, year = {2024}, author = {Horowitz, T and Dudouet, P and Campion, JY and Kaphan, E and Radulesco, T and Gonzalez, S and Cammilleri, S and Ménard, A and Guedj, E}, title = {Persistent brain metabolic impairment in long COVID patients with persistent clinical symptoms: a nine-month follow-up [[18]F]FDG-PET study.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {51}, number = {11}, pages = {3215-3222}, pmid = {38862619}, issn = {1619-7089}, support = {2007/09//PHRC/ ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/complications/metabolism ; *Fluorodeoxyglucose F18 ; Male ; Female ; Middle Aged ; *Brain/diagnostic imaging/metabolism ; *Positron-Emission Tomography ; Aged ; Adult ; Follow-Up Studies ; Retrospective Studies ; Radiopharmaceuticals/pharmacokinetics ; }, abstract = {PURPOSE: A hypometabolic profile involving the limbic areas, brainstem and cerebellum has been identified in long COVID patients using [[18]F]fluorodeoxyglucose (FDG)-PET. This study was conducted to evaluate possible recovery of brain metabolism during the follow-up of patients with prolonged symptoms.

METHODS: Fifty-six adults with long COVID who underwent two brain [[18]F]FDG-PET scans in our department between May 2020 and October 2022 were retrospectively analysed, and compared to 51 healthy subjects. On average, PET1 was performed 7 months (range 3-17) after acute COVID-19 infection, and PET2 was performed 16 months (range 8-32) after acute infection, because of persistent severe or disabling symptoms, without significant clinical recovery. Whole-brain voxel-based analysis compared PET1 and PET2 from long COVID patients to scans from healthy subjects (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected) and PET1 to PET2 (with the same threshold, and secondarily with a less constrained threshold of p-voxel < 0.005 uncorrected, p-cluster < 0.05 uncorrected). Additionally, a region-of-interest (ROI) semiquantitative anatomical approach was performed for the same comparisons (p < 0.05, corrected).

RESULTS: PET1 and PET2 revealed voxel-based hypometabolisms consistent with the previously reported profile in the literature. This between-group analysis comparing PET1 and PET2 showed minor improvements in the pons and cerebellum (8.4 and 5.2%, respectively, only significant under the less constrained uncorrected p-threshold); for the pons, this improvement was correlated with the PET1-PET2 interval (r = 0.21, p < 0.05). Of the 14,068 hypometabolic voxels identified on PET1, 6,503 were also hypometabolic on PET2 (46%). Of the 7,732 hypometabolic voxels identified on PET2, 6,094 were also hypometabolic on PET1 (78%). The anatomical ROI analysis confirmed the brain hypometabolism involving limbic region, the pons and cerebellum at PET1 and PET2, without significant changes between PET1 and PET2.

CONCLUSION: Subjects with persistent symptoms of long COVID exhibit durable deficits in brain metabolism, without progressive worsening.}, } @article {pmid38862591, year = {2024}, author = {Prasanth, MI and Wannigama, DL and Reiersen, AM and Thitilertdecha, P and Prasansuklab, A and Tencomnao, T and Brimson, S and Brimson, JM}, title = {A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13462}, pmid = {38862591}, issn = {2045-2322}, support = {Sys_66_007_3700_001//the Ratchadaprisk Sompoch Endowment Fund (2023) Chulalongkorn University/ ; }, mesh = {*Fluvoxamine/therapeutic use ; Humans ; *COVID-19 Drug Treatment ; *COVID-19/mortality ; *SARS-CoV-2/isolation & purification/drug effects ; Treatment Outcome ; Clinical Deterioration ; Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects/administration & dosage ; }, abstract = {There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes.}, } @article {pmid38862569, year = {2024}, author = {Bland, AR and Barraclough, M and Trender, WR and Mehta, MA and Hellyer, PJ and Hampshire, A and Penner, IK and Elliott, R and Harenwall, S}, title = {Profiles of objective and subjective cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve individuals.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13368}, pmid = {38862569}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; *Cognition ; SARS-CoV-2/isolation & purification ; Fatigue ; Neuropsychological Tests ; Surveys and Questionnaires ; Stress, Psychological ; Cognitive Dysfunction/etiology/virology/physiopathology ; Aged ; Self Report ; }, abstract = {Post-COVID Syndrome has emerged as a significant public health concern worldwide with increasing evidence to suggest that individuals who have had an acute COVID-19 infection report lingering memory and attention difficulties, even in individuals who have fully recovered and no longer experiencing symptoms of COVID-19. The present study sought to investigate the profile of objective and subjective cognitive difficulties in people who have Post-COVID Syndrome, people who have fully recovered from an acute COVID infection and people who have never had COVID-19. We further sought to explore the extent to which self-reported fatigue and stress are related to subjective and objective cognitive difficulties. 162 participants including 50 people living with Post-COVID Syndrome, 59 people who have had COVID-19 but have fully recovered and 53 people who have never experienced symptoms of COVID-19 and had never tested positive for COVID-19 were recruited from Academic Prolific to complete a series of online questionnaires and neurocognitive tasks. Subjective cognitive function was measured using the Cognitive Failures Questionnaire and objective cognitive function was measured using the Cognitron cognitive test battery. We found that objective and subjective measures of cognitive function were not significantly related, suggesting that self-reports of "brain fog" are not reflecting objectively measured cognitive dysfunction. A MANOVA revealed that subjective cognitive deficits were driven by heightened perceived stress and fatigue and not significantly related to COVID-19 status. Objective cognitive function, however, was significantly related to perceived stress and COVID status whereby we observed significant objective cognitive deficits in people who have been exposed to an acute COVID-19 infection regardless of whether they had Post-COVID Syndrome or had fully recovered, as compared to people who had never had COVID-19. This suggests that an acute infection can have long term effects on cognitive function, even without persistent COVID-19 symptoms. Encouragingly, objective cognitive function was significantly associated with time since initial infection showing that cognitive deficits improved over time for people who had recovered from COVID-19. However, we did not observe the same improvement in individuals with Post-COVID Syndrome and observed that cognitive dysfunction was significantly related to the number of neurological symptoms presently experienced. These results add to the accumulating literature that COVID-19 is associated with significant cognitive difficulties following a COVID-19 infection, which appear to improve over time for those who have recovered from COVID-19 yet persist in people living with Post-COVID Syndrome.}, } @article {pmid38861652, year = {2024}, author = {Barth, S and Kulie, P and Monroe, A and Horberg, M and Castel, A and , }, title = {Prevalence and risk factors for post-COVID conditions of COVID-19 among persons with HIV in Washington, DC.}, journal = {AIDS care}, volume = {}, number = {}, pages = {1-11}, pmid = {38861652}, issn = {1360-0451}, support = {R24 AI152598/AI/NIAID NIH HHS/United States ; UM1 AI069503/AI/NIAID NIH HHS/United States ; }, abstract = {Post-COVID conditions (long COVID) are defined as COVID symptoms persisting 28 days post-initial infection. The limited research available on the prevalence and experiences of post-COVID conditions among persons with HIV (PWH) indicates potential increased risk for post-COVID conditions. The purpose of this study was to characterize prevalence, symptom clustering, impact, and potential risk factors of post-COVID conditions among PWH. Data come from the COVID-19 survey, conducted as a sub-study of the DC Cohort Longitudinal HIV Study, an ongoing study of over 12,000 PWH living in Washington, DC. Survey data were matched to electronic medical record data. Prevalence estimates and multivariable logistic regression analyses were calculated comparing those with and without post-COVID conditions. The prevalence of post-COVID conditions among PWH was 46% with no significant differences among demographic or HIV measures. Those with history of asthma were more likely to report post-COVID conditions symptoms. Among those with post-COVID conditions, 81% reported three or more initial COVID symptoms. Retired/disabled PWH were more likely to report post-COVID conditions compared to employed (aOR = 2.37, 95% CI = 1.06, 5.33). Post-COVID conditions significantly limited activities of daily living. Programs are needed to address the long-term impact of post-COVID conditions on activities of daily living among PWH.}, } @article {pmid38860901, year = {2024}, author = {Teopiz, KM and Kwan, ATH and Le, GH and Guo, Z and Badulescu, S and Ceban, F and Meshkat, S and Di Vincenzo, JD and d'Andrea, G and Cao, B and Ho, R and Rhee, TG and Dev, DA and Phan, L and Subramaniapillai, M and Mansur, RB and Rosenblat, JD and McIntyre, RS}, title = {Association between fatigue and depressive symptoms in persons with post-COVID-19 condition: a post hoc analysis.}, journal = {Current medical research and opinion}, volume = {40}, number = {7}, pages = {1203-1209}, doi = {10.1080/03007995.2024.2360647}, pmid = {38860901}, issn = {1473-4877}, mesh = {Humans ; Female ; Male ; *Fatigue/etiology ; *COVID-19/complications/psychology ; Middle Aged ; *Depression/epidemiology ; Adult ; Post-Acute COVID-19 Syndrome ; Double-Blind Method ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; }, abstract = {OBJECTIVE: Post-COVID-19 Condition (PCC) is a prevalent, persistent and debilitating phenomenon occurring three or more months after resolution of acute COVID-19 infection. Fatigue and depressive symptoms are commonly reported in PCC. We aimed to further characterize PCC by assessing the relationship between fatigue and depressive symptom severity in adults with PCC.

METHODS: A post hoc analysis was conducted on data retrieved from a randomized, double-blinded, placebo-controlled study evaluating vortioxetine for cognitive deficits in persons with PCC. We sought to determine the relationship between baseline fatigue [i.e. Fatigue Severity Scale (FSS) total score] and baseline depressive symptom severity [i.e. 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16) total score] in adults with PCC.

RESULTS: The statistical analysis included baseline data from 142 participants. After adjusting for age, sex, education, employment status, history of major depressive disorder (MDD) diagnosis, self-reported physical activity, history of documented acute SARS-CoV-2 infection and body mass index (BMI), baseline FSS was significantly correlated with baseline QIDS-SR-16 (β = 0.825, p = .001).

CONCLUSION: In our sample, baseline measures of fatigue and depressive symptoms are correlated in persons living with PCC. Individuals presenting with PCC and fatigue should be screened for the presence and severity of depressive symptoms. Guideline-concordant care should be prescribed for individuals experiencing clinically significant depressive symptoms. Fatigue and depressive symptom severity scores were not pre-specified as primary objectives of the study. Multiple confounding factors (i.e. disturbance in sleep, anthropometrics and cognitive impairment) were not collected nor adjusted for in the analysis herein.

TRIAL REGISTRATION: Unrestricted Research Grant from H. Lundbeck A/S, Copenhagen, Denmark. ClinicalTrials.gov Identifier: NCT05047952.}, } @article {pmid38860630, year = {2024}, author = {Parkin, A and Rayner, C and Mir, G and O'Connor, RJ}, title = {Vocational rehabilitation for Long Covid: a roadmap for recovery.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {4}, pages = {262-265}, doi = {10.1093/occmed/kqae020}, pmid = {38860630}, issn = {1471-8405}, mesh = {Humans ; *COVID-19/rehabilitation/prevention & control ; *Rehabilitation, Vocational/methods ; *SARS-CoV-2 ; Return to Work ; }, } @article {pmid38860534, year = {2024}, author = {}, title = {Correction to: De-black-boxing health AI: demonstrating reproducible machine learning computable phenotypes using the N3C-RECOVER Long COVID model in the All of Us data repository.}, journal = {Journal of the American Medical Informatics Association : JAMIA}, volume = {31}, number = {8}, pages = {1799}, doi = {10.1093/jamia/ocae154}, pmid = {38860534}, issn = {1527-974X}, } @article {pmid38857785, year = {2024}, author = {Vinson, AJ and Schissel, M and Anzalone, AJ and Dai, R and French, ET and Olex, AL and Lee, SB and Ison, M and Mannon, RB and , }, title = {The prevalence of postacute sequelae of coronavirus disease 2019 in solid organ transplant recipients: Evaluation of risk in the National COVID Cohort Collaborative.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {24}, number = {9}, pages = {1675-1689}, pmid = {38857785}, issn = {1600-6143}, support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; K23 DK124654/DK/NIDDK NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; *Organ Transplantation/adverse effects ; *Transplant Recipients/statistics & numerical data ; Aged ; *SARS-CoV-2 ; Adult ; Prevalence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; United States/epidemiology ; Retrospective Studies ; Immunocompromised Host ; Propensity Score ; }, abstract = {Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status.}, } @article {pmid38855289, year = {2024}, author = {Pandey, S and Bapat, V and Abraham, JN and Abraham, NM}, title = {Long COVID: From olfactory dysfunctions to viral Parkinsonism.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {10}, number = {2}, pages = {137-147}, pmid = {38855289}, issn = {2589-1081}, abstract = {Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019 (COVID-19). This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges. Historically, the surge of neurological disorders followed the viral pandemics, for example, the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza. During and after COVID-19 infection, the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease. These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications. In this manuscript, we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective. Further, we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.}, } @article {pmid38855287, year = {2024}, author = {Tervo, JP and Jacobson, PT and Vilarello, BJ and Saak, TM and Caruana, FF and Gallagher, LW and Gary, JB and Gudis, DA and Joseph, PV and Devanand, DP and Goldberg, TE and Overdevest, JB}, title = {Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {10}, number = {2}, pages = {79-87}, pmid = {38855287}, issn = {2589-1081}, abstract = {OBJECTIVES: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD.

METHODS: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available.

RESULTS: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004).

CONCLUSIONS: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.}, } @article {pmid38855286, year = {2024}, author = {Kim, S and Finlay, JB and Ko, T and Goldstein, BJ}, title = {Long-term olfactory loss post-COVID-19: Pathobiology and potential therapeutic strategies.}, journal = {World journal of otorhinolaryngology - head and neck surgery}, volume = {10}, number = {2}, pages = {148-155}, pmid = {38855286}, issn = {2589-1081}, abstract = {An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the early phases of the COVID-19 pandemic. In most COVID-19 patients, olfaction recovers over the course of a few weeks. However, a lasting partial or complete loss of smell, often associated with distorted olfactory perceptions termed parosmia, has emerged as a widespread problem impacting at least 5%-10% of those who experience anosmia due to COVID-19. Our inability to offer effective therapies to this hyposmic or anosmic population, comprising millions of patients, highlights an enormous unmet need for the medical system. Here, we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection, focusing on how the virus interacts with the peripheral olfactory system, a major site of viral infection. We also explore the problem of long-COVID olfactory dysfunction, which may accompany other persistent systemic disorders collectively termed postacute sequelae of COVID-19. Specifically, we discuss an emerging model focused on unresolved immune cell activity driving ongoing dysfunction. Finally, we review current and future therapeutic approaches aimed at restoring olfactory function.}, } @article {pmid38854872, year = {2024}, author = {Igarashi, S and Okita, K and Hayashi, D and Yamazaki, R and Matsuda, Y and Noda, T and Watanabe, K and Kito, S}, title = {Neuroinflammatory Alterations in Treatment-Resistant Depression Secondary to Long COVID by Repetitive Transcranial Magnetic Stimulation (rTMS): A Case Report.}, journal = {Psychiatric research and clinical practice}, volume = {6}, number = {2}, pages = {63-64}, pmid = {38854872}, issn = {2575-5609}, } @article {pmid38850628, year = {2024}, author = {Panagea, E and Messinis, L and Petri, MC and Liampas, I and Anyfantis, E and Nasios, G and Patrikelis, P and Kosmidis, M}, title = {Neurocognitive Impairment in Long COVID: A Systematic Review.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {}, number = {}, pages = {}, doi = {10.1093/arclin/acae042}, pmid = {38850628}, issn = {1873-5843}, abstract = {OBJECTIVE: Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome.

METHODS: A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included.

RESULTS: Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated.

CONCLUSIONS: In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.}, } @article {pmid38850204, year = {2024}, author = {Mullard, J and Mir, G and Herbert, C and Evans, S and , }, title = {'You're just a Guinea pig': Exploring the barriers and impacts of living with long COVID-19: A view from the undiagnosed.}, journal = {Sociology of health & illness}, volume = {46}, number = {8}, pages = {1602-1625}, doi = {10.1111/1467-9566.13795}, pmid = {38850204}, issn = {1467-9566}, support = {COV-LT2-0016//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/psychology ; United Kingdom ; *SARS-CoV-2 ; Qualitative Research ; Post-Acute COVID-19 Syndrome ; Female ; Male ; Interviews as Topic ; Pandemics ; }, abstract = {The COVID-19 pandemic had a disproportionate impact on ethnically minoritised and other marginalised communities, yet little is known about the impacts of long COVID-19 (LC) on this group. Living with LC takes its toll both physically, emotionally and financially and even more so when a diagnosis is hard to come by. By using qualitative interviews centring the view of undiagnosed and marginalised communities already classed as 'underserved' in the medical literature, we show the range of barriers and impacts faced by these groups in the UK, and the strategies of resilience they use. Whether trapped on a 'diagnostic odyssey' at the level of primary care, struggling to maintain employment and businesses, or managing family commitments, we argue many minoritised communities are caught in a liminal space of misrecognition, invalidation and ambiguity. We show how these impacts are generated by tensions and challenges in the process and categorisation of diagnosis, and how this effects the daily lives of many individuals already on the receiving end of health inequity. We also offer some examples and suggestions for best practices.}, } @article {pmid38849462, year = {2024}, author = {Xue, P and Merikanto, I and Delale, EA and Bjelajac, A and Yordanova, J and Chan, RNY and Korman, M and Mota-Rolim, SA and Landtblom, AM and Matsui, K and Reis, C and Penzel, T and Inoue, Y and Nadorff, MR and Holzinger, B and Morin, CM and Espie, CA and Plazzi, G and De Gennaro, L and Chung, F and Bjorvatn, B and Wing, YK and Dauvilliers, Y and Partinen, M and Benedict, C}, title = {Associations between obesity, a composite risk score for probable long COVID, and sleep problems in SARS-CoV-2 vaccinated individuals.}, journal = {International journal of obesity (2005)}, volume = {48}, number = {9}, pages = {1300-1306}, pmid = {38849462}, issn = {1476-5497}, mesh = {Humans ; *Obesity/complications/epidemiology ; Female ; *COVID-19/prevention & control/epidemiology/immunology/complications ; Adult ; Male ; Middle Aged ; *SARS-CoV-2/immunology ; Aged ; *COVID-19 Vaccines ; *Sleep Wake Disorders/epidemiology ; Adolescent ; Young Adult ; Aged, 80 and over ; Body Mass Index ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Vaccination/statistics & numerical data ; }, abstract = {BACKGROUND: Preliminary data suggests that obesity might hasten the decline in mRNA vaccine-induced immunity against SARS-CoV-2. However, whether this renders individuals with obesity more susceptible to long COVID symptoms post-vaccination remains uncertain. Given sleep's critical role in immunity, exploring the associations between obesity, probable long COVID symptoms, and sleep disturbances is essential.

METHODS: We analyzed data from a survey of 5919 adults aged 18 to 89, all of whom received two SARS-CoV-2 mRNA vaccinations. Participants were categorized into normal weight, overweight, and obesity groups based on ethnicity-specific BMI cutoffs. The probability of long COVID was evaluated using the Post-Acute Sequelae of SARS-CoV-2 (PASC) score, as our survey did not permit confirmation of acute SARS-CoV-2 infection through methods such as antibody testing. Additionally, sleep patterns were assessed through questionnaires.

RESULTS: Participants with obesity exhibited a significantly higher adjusted odds ratio (OR) of having a PASC score of 12 or higher, indicative of probable long COVID in our study, compared to those with normal weight (OR: 1.55, 95% CI: 1.05, 2.28). No significant difference was observed for overweight individuals (OR: 0.92 [95% CI: 0.63, 1.33]). Both obesity and probable long COVID were associated with increased odds of experiencing a heightened sleep burden, such as the presence of obstructive sleep apnea or insomnia (P < 0.001). However, no significant interaction between BMI and probable long COVID status was found.

CONCLUSIONS: Even post-vaccination, individuals with obesity may encounter a heightened risk of experiencing prolonged COVID-19 symptoms. However, confirming our observations necessitates comprehensive studies incorporating rigorous COVID infection testing, such as antibody assays - unavailable in our anonymous survey. Additionally, it is noteworthy that the correlation between probable long COVID and sleep disturbances appears to be independent of BMI.}, } @article {pmid38848177, year = {2024}, author = {Tavares-Júnior, JWL and Ciurleo, GCV and Feitosa, EAAF and Oriá, RB and Braga-Neto, P}, title = {The Clinical Aspects of COVID and Alzheimer's Disease: A Round-Up of Where Things Stand and Are Headed.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {99}, number = {4}, pages = {1159-1171}, doi = {10.3233/JAD-231368}, pmid = {38848177}, issn = {1875-8908}, mesh = {Humans ; *Alzheimer Disease ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cognitive Dysfunction/etiology ; }, abstract = {The link between long COVID-19 and brain/cognitive impairments is concerning and may foster a worrisome worldwide emergence of novel cases of neurodegenerative diseases with aging. This review aims to update the knowledge, crosstalk, and possible intersections between the Post-COVID Syndrome (PCS) and Alzheimer's disease (AD). References included in this review were obtained from PubMed searches conducted between October 2023 and November 2023. PCS is a very heterogenous and poorly understood disease with recent evidence of a possible association with chronic diseases such as AD. However, more scientific data is required to establish the link between PCS and AD.}, } @article {pmid38848092, year = {2024}, author = {Fang, Z and Ahrnsbrak, R and Rekito, A}, title = {Evidence Mounts That About 7% of US Adults Have Had Long COVID.}, journal = {JAMA}, volume = {332}, number = {1}, pages = {5-6}, doi = {10.1001/jama.2024.11370}, pmid = {38848092}, issn = {1538-3598}, mesh = {Adult ; Humans ; COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; United States/epidemiology ; Male ; Female ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Hispanic or Latino ; Asian ; White ; Black or African American ; }, } @article {pmid38847905, year = {2024}, author = {Brandes, LE and Orme, D and Bermeo-Ovalle, A and Sierra Morales, F}, title = {Clinical and diagnostic features of long-COVID patients presenting with neurologic symptoms in Chicago.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {131}, number = {8}, pages = {961-969}, pmid = {38847905}, issn = {1435-1463}, mesh = {Humans ; *COVID-19/complications/diagnosis ; Chicago/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Nervous System Diseases/etiology/diagnosis ; Adult ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; }, abstract = {Long COVID, a condition characterized by persistent symptoms after COVID-19 infection, is increasingly being recognized worldwide. Neurologic symptoms are frequently reported in survivors of COVID-19, making it crucial to better understand this phenomenon both on a societal scale and for the quality of life of these patients. Between January 1, 2020, and July 31, 2022, Illinois (IL) had a standardized cumulative death rate that ranked it 24th out of the 51 states in the United States (US). However, the US had one of the highest per capita COVID-19 death rates among large, high-income countries. [Bollyky T. et al. 2023] As a result of the increased number of COVID-19 infections, there was a rise in the number of patients experiencing Long COVID. At our neuro-infectious disease clinic in Chicago (IL), we observed an increasing number of patients presenting with cognitive and other neurologic symptoms after contracting COVID-19. Initially, we needed to provide these individuals with a better understanding of their condition and expected outcomes. We were thus motivated to further evaluate this group of patients for any patterns in presentation, neurologic findings, and diagnostic testing that would help us better understand this phenomenon. We aim to contribute to the growing body of research on Long COVID, including its presentation, diagnostic testing results, and outcomes to enlighten the long COVID syndrome. We hypothesize that the neurological symptoms resulting from long COVID persist for over 12 months. We conducted a retrospective analysis of clinical data from 44 patients with long-COVID. Cognitive symptoms were the most common presenting concern. Abnormalities in Montreal Cognitive Assessment, electroencephalogram, serum autoantibody testing, and cerebrospinal fluid were found in minority subsets of our cohort. At 12 months, most patients continue to experience neurologic symptoms, though more than half reported moderate or marked improvement compared to initial presentation. Although most of the patients in this study did not show a consistent occurrence of symptoms suggesting a cohesive underlying etiology, our clinical data demonstrated some features of Long COVID patients in Chicago (IL) that could lead to new research avenues, helping us better understand this syndrome that affects patients worldwide.}, } @article {pmid38846912, year = {2024}, author = {Jose, C}, title = {Breaking through the noise: how to unveil the cognitive impact of long COVID on pre-existing conditions with executive dysfunctions?.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1390214}, pmid = {38846912}, issn = {1664-0640}, } @article {pmid38846354, year = {2024}, author = {Zhang, Y and Chen, S and Tian, Y and Fu, X}, title = {Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1407261}, pmid = {38846354}, issn = {2235-2988}, mesh = {Humans ; *COVID-19/virology ; *SARS-CoV-2/pathogenicity ; *Virus Replication ; *Host-Pathogen Interactions ; Antiviral Agents/therapeutic use ; Host Microbial Interactions ; }, abstract = {SARS-CoV-2 is the causative virus of the devastating COVID-19 pandemic that results in an unparalleled global health and economic crisis. Despite unprecedented scientific efforts and therapeutic interventions, the fight against COVID-19 continues as the rapid emergence of different SARS-CoV-2 variants of concern and the increasing challenge of long COVID-19, raising a vast demand to understand the pathomechanisms of COVID-19 and its long-term sequelae and develop therapeutic strategies beyond the virus per se. Notably, in addition to the virus itself, the replication cycle of SARS-CoV-2 and clinical severity of COVID-19 is also governed by host factors. In this review, we therefore comprehensively overview the replication cycle and pathogenesis of SARS-CoV-2 from the perspective of host factors and host-virus interactions. We sequentially outline the pathological implications of molecular interactions between host factors and SARS-CoV-2 in multi-organ and multi-system long COVID-19, and summarize current therapeutic strategies and agents targeting host factors for treating these diseases. This knowledge would be key for the identification of new pathophysiological aspects and mechanisms, and the development of actionable therapeutic targets and strategies for tackling COVID-19 and its sequelae.}, } @article {pmid38845871, year = {2024}, author = {Zhao, LM and Lancaster, AC and Patel, R and Zhang, H and Duong, TQ and Jiao, Z and Lin, CT and Healey, T and Wright, T and Wu, J and Bai, HX}, title = {Association of clinical and imaging characteristics with pulmonary function testing in patients with Long-COVID.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e31751}, pmid = {38845871}, issn = {2405-8440}, abstract = {PURPOSE: The purpose of this study is to identify clinical and imaging characteristics associated with post-COVID pulmonary function decline.

METHODS: This study included 22 patients recovering from COVID-19 who underwent serial spirometry pulmonary function testing (PFT) before and after diagnosis. Patients were divided into two cohorts by difference between baseline and post-COVID follow-up PFT: Decline group (>10 % decrease in FEV1), and Stable group (≤10 % decrease or improvement in FEV1). Demographic, clinical, and laboratory data were collected, as well as PFT and chest computed tomography (CT) at the time of COVID diagnosis and follow-up. CTs were semi-quantitatively scored on a five-point severity scale for disease extent in each lobe by two radiologists. Mann-Whitney U-tests, T-tests, and Chi-Squared tests were used for comparison. P-values <0.05 were considered statistically significant.

RESULTS: The Decline group had a higher proportion of neutrophils (79.47 ± 4.83 % vs. 65.45 ± 10.22 %; p = 0.003), a higher absolute neutrophil count (5.73 ± 2.68 × 10[9]/L vs. 3.43 ± 1.74 × 10[9]/L; p = 0.031), and a lower proportion of lymphocytes (9.90 ± 4.20 % vs. 21.21 ± 10.97 %; p = 0.018) compared to the Stable group. The Decline group also had significantly higher involvement of ground-glass opacities (GGO) on follow-up chest CT [8.50 (4.50, 14.50) vs. 3.0 (1.50, 9.50); p = 0.032] and significantly higher extent of reticulations on chest CT at time of COVID diagnosis [6.50 (4.00, 9.00) vs. 2.00 (0.00, 6.00); p = 0.039] and follow-up [5.00 (3.00, 13.00) vs. 2.00 (0.00, 5.00); p = 0.041]. ICU admission was higher in the Decline group than in the Stable group (71.4 % vs. 13.3 %; p = 0.014).

CONCLUSIONS: This study provides novel insight into factors influencing post-COVID lung function, irrespective of pre-existing pulmonary conditions. Our findings underscore the significance of neutrophil counts, reduced lymphocyte counts, pulmonary reticulation on chest CT at diagnosis, and extent of GGOs on follow-up chest CT as potential indicators of decreased post-COVID lung function. This knowledge may guide prediction and further understanding of long-term sequelae of COVID-19 infection.}, } @article {pmid38844389, year = {2024}, author = {Monteiro, S and Dessenne, C and Perquin, M}, title = {Long COVID cognitive sequelae 6 months postinfection and beyond: a scoping review protocol.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e084798}, pmid = {38844389}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *SARS-CoV-2 ; Cognitive Dysfunction/etiology ; Research Design ; Systematic Reviews as Topic ; Cognition ; }, abstract = {INTRODUCTION: The novel and expanding field of long COVID research has undergone diverse methodological approaches in recent years. This protocol lays out the methodological approach, which aims at identifying nuances in current research. It underscores the necessity for a more precise understanding of prolonged cognitive sequelae and their relation to initial disease severity. The findings will add valuable insights for the development of targeted rehabilitation, healthcare interventions and thereby aid patients, clinicians, policymakers and researchers. Our upcoming research is introduced here.

METHODS AND ANALYSIS: To map current research in the field, a scoping review will be conducted and documented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review Extension standards. A systematic search of scientific databases (PubMed, EMBASE), presented 1409 eligible results, published up to 21 December 2023. After removal of duplicates, 925 articles were extracted for screening. Two independent reviewers will screen for titles, abstracts and full texts, to extract data, which will then be organised using charting software. Data for various variables, that is, journal info, studied population demographics, study design, long COVID related data, cognitive outcomes and neuropsychological tests will be gathered. Descriptive analyses, evidence gap maps, heat map quantifications and narrative synthesis will be conducted for reporting of results.This scoping review has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/JHFX6).

ETHICS AND DISSEMINATION: Ethical approval is not required, as the study does not involve human participants. The findings will be disseminated through a publication in a scientific journal and within the professional network.}, } @article {pmid38843604, year = {2024}, author = {Pham, T and Morin, L and Savale, L and Colle, R and Figueiredo, S and Harrois, A and Gasnier, M and Lecoq, AL and Meyrignac, O and Noel, N and Abdo, A and Baudry, E and Bellin, MF and Beurnier, A and Choucha, W and Corruble, E and Dortet, L and Gosset, E and Hardy-Leger, I and Quinque, M and Radiguer, F and Sportouch, S and Verny, C and Wyplosz, B and Zaidan, M and Becquemont, L and Montani, D and Monnet, X}, title = {Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19.}, journal = {Respiratory medicine and research}, volume = {86}, number = {}, pages = {101099}, doi = {10.1016/j.resmer.2024.101099}, pmid = {38843604}, issn = {2590-0412}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cognitive Dysfunction/epidemiology/etiology ; Cohort Studies ; *COVID-19/epidemiology/complications ; Depression/epidemiology ; Dyspnea/epidemiology/etiology ; Fatigue/etiology/epidemiology ; *Hospitalization/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Prevalence ; Respiratory Function Tests ; Time Factors ; }, abstract = {BACKGROUND AND OBJECTIVES: Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19.

METHODS: A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge. Patients with relevant symptoms at 16 months, patients who presented symptoms at four months, and all intensive care unit patients were invited for assessment at an outpatient facility. At telephone consultation, respiratory, cognitive, and functional symptoms were assessed. Patients underwent pulmonary function tests, lung CT scans, and psychometric and cognitive tests at the outpatient facility.

RESULTS: Among 478 patients evaluated four months after discharge, 317 (67 %) were assessed at telephone consultation and 124 at ambulatory assessment. At telephone assessment, ≥1 new symptom was reported by 216 patients (68 %), mainly fatigue (53 %), dyspnea (37 %), and memory difficulties (24 %). Seventy-nine patients (25 %) were asymptomatic at four months but declared ≥1 symptom one year later. In patients evaluated twice, the prevalence of cognitive impairment was 45 % at four months and 40 % at 16 months. Depression and post-traumatic symptoms prevalence remained stable, and the prevalence of anxiety significantly decreased. Dysfunctional breathing was detected in 32 % of patients. At 16 months after discharge, lung CT-scan exhibited abnormalities in 30/80 patients (38 %), compared to 52/85 patients (61 %) at four months.

CONCLUSION: At 16 months after hospitalization for COVID-19, 68 % of patients declared symptoms, including patients whose symptoms appeared between 4 and 16 months.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT04704388.}, } @article {pmid38843555, year = {2024}, author = {Jeffreys, M and McKenzie, F and Irurzun Lopez, M and Russell, L and Ellison-Loschmann, L}, title = {Long COVID impacts people's ability to work: cross-sectional study in Aotearoa New Zealand.}, journal = {The New Zealand medical journal}, volume = {137}, number = {1596}, pages = {102-104}, doi = {10.26635/6965.6530}, pmid = {38843555}, issn = {1175-8716}, support = {//New Zealand Ministry of Health/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; New Zealand/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Adult ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Employment/statistics & numerical data ; }, } @article {pmid38843198, year = {2024}, author = {Binswanger, IA and Palmer-Toy, DE and Barrow, JC and Narwaney, KJ and Bruxvoort, KJ and Kraus, CR and Lyons, JA and Lam, JA and Glanz, JM}, title = {Assessing the association between antibody status and symptoms of long COVID: A multisite study.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0304262}, pmid = {38843198}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *COVID-19/immunology/epidemiology ; Middle Aged ; *Antibodies, Viral/blood ; *SARS-CoV-2/immunology ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Colorado/epidemiology ; Cohort Studies ; RNA, Viral/blood ; California/epidemiology ; Immunity, Humoral ; }, abstract = {The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12-18). Three quarters (74.5%) reported having had COVID-19. Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function. As expected, physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19). Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.}, } @article {pmid38841775, year = {2024}, author = {Ronconi, G and Codazza, S and Ariani, M and LA Cagnina, F and Scrima, R and Coraci, D and Ferrara, PE}, title = {An update of the literature about rehabilitation tools used in the treatment of COVID-19-related disabilities: a systematic review of literature.}, journal = {Panminerva medica}, volume = {66}, number = {3}, pages = {309-316}, doi = {10.23736/S0031-0808.24.05098-5}, pmid = {38841775}, issn = {1827-1898}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; Quality of Life ; Telerehabilitation ; Exercise Therapy/methods ; SARS-CoV-2 ; Electric Stimulation Therapy/methods ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Physical Therapy Modalities ; Virtual Reality ; }, abstract = {INTRODUCTION: The role of rehabilitation during and after the COVID-19 pandemia was influenced by the progressive acquisition of knowledge on the pathology with the adaptation of the rehabilitative instruments to the heterogeneous impairments of the patients. The aim of this systematic review is to describe the effects of the rehabilitation tools applied in the last three years in the different phases of the COVID-19 disease.

EVIDENCE ACQUISITION: A literature search of MEDLINE (PubMed), Scopus and Physiotherapy Evidence Database (PEDro) was conducted. 2994 participants were included in this systematic review: 1225 patients for acute-COVID, 1331 patients for post-COVID, 438 patients for long-COVID.

EVIDENCE SYNTHESIS: Of the initial 907 hits only 45 randomized controlled trials were included. The Cochrane library assessment tool was used to evaluate the risk of bias. The trials selected studied the effects of respiratory rehabilitation alone or in association with exercises, tele-rehabilitation, endurance training, virtual reality, electrostimulations in different settings and phases of the infection with the evaluation of clinical, quality of life and impairment outcome measures.

CONCLUSIONS: All the rehabilitations tool were used based on the experts' opinion and on the rules of good clinical practice, during and after the pandemic period. Despite the heterogeneity of the studies, the different outcome measures and the small sample sizes, pulmonary rehabilitation, tele-rehabilitation and low/moderate intensity aerobic and endurance exercises seemed to improve clinical and quality of life outcomes at short (8 weeks) and mean time (2 months) after treatments in all phases of the infection.}, } @article {pmid38841730, year = {2024}, author = {Granvik, C and Andersson, S and Andersson, L and Brorsson, C and Forsell, M and Ahlm, C and Normark, J and Edin, A}, title = {Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up.}, journal = {Brain and behavior}, volume = {14}, number = {6}, pages = {e3574}, pmid = {38841730}, issn = {2162-3279}, support = {2020-06235//Swedish Research Council/ ; 2016-06514//Swedish Research Council/ ; 20200325//Hjärt-Lungfonden/ ; 20210078//Hjärt-Lungfonden/ ; VC-2020-0015//Knut och Alice Wallenbergs Stiftelse/ ; VLL 1925-2017//Knut och Alice Wallenbergs Stiftelse/ ; FS 2.1.6-849-20//Knut och Alice Wallenbergs Stiftelse/ ; RV-938855//County Council of Västerbotten/ ; RV-939393//County Council of Västerbotten/ ; }, mesh = {Humans ; *COVID-19/complications/diagnosis ; Male ; Female ; *Olfaction Disorders/etiology/diagnosis/physiopathology ; Middle Aged ; *Quality of Life ; Prospective Studies ; *Neuropsychological Tests ; Aged ; Follow-Up Studies ; Adult ; Cognitive Dysfunction/etiology/physiopathology/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life.

METHODS: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1-3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year.

RESULTS: Objectively assessed olfactory dysfunction at 1-3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+.

CONCLUSION: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.}, } @article {pmid38836048, year = {2024}, author = {Olawore, O and Turner, LE and Evans, MD and Johnson, SG and Huling, JD and Bramante, CT and Buse, JB and Stürmer, T and , }, title = {Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications.}, journal = {Clinical epidemiology}, volume = {16}, number = {}, pages = {379-393}, pmid = {38836048}, issn = {1179-1349}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users.

METHODS: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023. Participants were adults ≥ 18 years with T2DM who had at least one outpatient healthcare encounter in health institutions in the United States prior to COVID-19 diagnosis. The outcome of PASC was defined based on the presence of a diagnosis code for the illness or using a predicted probability based on a machine learning algorithm. We estimated the 3-month and 6-month risk of PASC and calculated crude and weighted risk ratios (RR), risk differences (RD), and differences in mean predicted probability.

RESULTS: We identified 5596 (mean age: 61.1 years; SD: 12.6) and 1451 (mean age: 64.9 years; SD 12.5) eligible prevalent users of metformin and SU/DPP4i respectively. We did not find a significant difference in risk of PASC at 3 months (RR = 0.86 [0.56; 1.32], RD = -3.06 per 1000 [-12.14; 6.01]), or at 6 months (RR = 0.81 [0.55; 1.20], RD = -4.91 per 1000 [-14.75, 4.93]) comparing prevalent users of metformin to prevalent users of SU/ DPP4i. Similar observations were made for the outcome definition using the ML algorithm.

CONCLUSION: The observed estimates in our study are consistent with a reduced risk of PASC among prevalent users of metformin, however the uncertainty of our confidence intervals warrants cautious interpretations of the results. A standardized clinical definition of PASC is warranted for thorough evaluation of the effectiveness of therapies under assessment for the prevention of PASC.}, } @article {pmid38834017, year = {2024}, author = {Donnelly, SC}, title = {Effective early strategy to prevent persistent olfactory and gustatory dysfunction in the long COVID syndrome: a randomized controlled trial.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {117}, number = {5}, pages = {311-312}, doi = {10.1093/qjmed/hcae079}, pmid = {38834017}, issn = {1460-2393}, mesh = {Humans ; *COVID-19/complications ; Female ; *Olfaction Disorders/etiology ; *Post-Acute COVID-19 Syndrome ; Male ; *Taste Disorders/etiology ; Middle Aged ; SARS-CoV-2 ; Aged ; }, } @article {pmid38833277, year = {2024}, author = {Talanki, AS and Bajaj, N and Trehan, T and Thirunavukkarasu, S}, title = {Incidence, Risk, and Clinical Course of New-Onset Diabetes in Long COVID: Protocol for a Systematic Review and Meta-Analysis of Cohort Studies.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e54853}, pmid = {38833277}, issn = {1929-0748}, mesh = {Humans ; *COVID-19/epidemiology ; *Systematic Reviews as Topic ; Incidence ; *Diabetes Mellitus/epidemiology ; *Meta-Analysis as Topic ; Cohort Studies ; Risk Factors ; SARS-CoV-2 ; Pandemics ; }, abstract = {BACKGROUND: COVID-19, an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors endure the lingering health effects of SARS-CoV-2, the pathogen that causes COVID-19. One of the diseases manifesting as a postacute sequela of COVID-19 (also known as "long COVID") is new-onset diabetes.

OBJECTIVE: The aim of this study is to examine the incidence of new-onset diabetes in patients with long COVID and assess the excess risk compared with individuals who tested negative for COVID-19. The study also aims to estimate the population-attributable fraction for COVID-19 as a risk factor for new-onset diabetes in long COVID and investigate the clinical course of new-onset diabetes cases.

METHODS: This is a protocol for a systematic review and meta-analysis. PubMed, MEDLINE, Embase, Scopus, and Web of Science databases will be systematically searched to identify articles published between December 2019 and July 2024. A comprehensive search strategy for each database will be developed using a combination of Medical Subject Headings terms, subject headings, and text words to identify eligible studies. Cohort studies and randomized controlled trials (only control arms) involving patients with COVID-19 of any age, with follow-up data on new-onset diabetes in long COVID, will be considered for inclusion. Controls will comprise individuals who tested negative for COVID-19, with or without other respiratory tract infections. Three independent reviewers (AST, NB, and TT) will perform article selection, data extraction, and quality assessment of the studies. A fourth reviewer (ST) will review the identified studies for final inclusion in the analysis. The random-effects DerSimonian-Laird models will be used to estimate the pooled incidence proportion (%), incidence rate of diabetes (per 1000 person-years), and risk ratio (with 95% CIs) for diabetes incidence.

RESULTS: A total of 1972 articles were identified through the initial search conducted in August 2023. After excluding duplicates, conducting title and abstract screening, and completing full-text reviews, 41 articles were found to be eligible for inclusion. The search will be updated in July 2024. Currently, data extraction is underway, and the meta-analysis is expected to be completed in August 2024. Publication of the study findings is anticipated by the end of 2024.

CONCLUSIONS: The study findings should provide valuable insights to inform both clinical practice and public health policies regarding the effective management of new-onset diabetes in patients with long COVID.

DERR1-10.2196/54853.}, } @article {pmid38833210, year = {2024}, author = {Dal Negro, RW and Turco, P and Povero, M}, title = {mRNA vaccines protect from the lung microvasculature injury and the capillary blood volume loss occurring in SARS-CoV-2 paucisymptomatic infections.}, journal = {Multidisciplinary respiratory medicine}, volume = {19}, number = {1}, pages = {}, pmid = {38833210}, issn = {1828-695X}, abstract = {INTRODUCTION: The reduction of lung capillary blood volume (Vc) had been identified as the microvascular injury mostly underlying the respiratory Long-COVID syndrome following post-COVID-19 pneumonia. The same kind of injury have been recently also found in several individuals after milder paucisymptomatic SARS-CoV-2 infections. Though current guidelines strongly recommend vac-cination, studies aimed to investigate the in vivo protection of anti-SARS-CoV-2 vaccines on lung microvascular targets still are missing to our best knowledge.

AIM: to assess the protection of mRNA vaccines from the reduction of lung capillary blood volume (Vc) caused by pauci-symptomatic SARS.CoV-2 infections in vaccinated compared to unvaccinated individuals.

METHODS: Non-smoking individuals with recent paucisymptomatic SARS-CoV-2 infection were divided into vaccinated and unvaccinated groups. Lung function parameters, including single-breath diffusing capacity and microvascular blood volume, were compared between groups.

RESULTS: fifty vaccinated and twenty-five unvaccinated well-matched individuals were studied. Differently than usual lung function parameters, only the single-breath simultaneous assessment of sDLCO, sDLNO/sDLCO ratio and Vc allowed to identify the occurrence of the lung microvascular injury with high sensitivity and specificity (p<0.001).

CONCLUSION: mRNA vaccines proved to exert a high protection from the loss of lung capillary blood volume (Vc) induced by SARS.CoV-2 paucisymptomatic infections (p<0.001). The availability of this non-invasive investigational model should be regarded as a very helpful tool for assessing and comparing in vivo the protective effect of mRNA vaccines on the human microvascular structures of the deep lung.}, } @article {pmid38831970, year = {2024}, author = {Dutra, LS and Shigaeff, N}, title = {Proposed protocol for post COVID-19 cognitive rehabilitation for attention and memory.}, journal = {Dementia & neuropsychologia}, volume = {18}, number = {}, pages = {e20230109}, pmid = {38831970}, issn = {1980-5764}, abstract = {UNLABELLED: Since the beginning of the COVID-19 pandemic, many people suffered from Long Covid Syndrome, in which affected individuals do not recover immediately after the end of the infectious and inflammatory process caused by the virus. The most common neuropsychological symptoms of this syndrome are: memory decline, lack of attention, anxiety and depression.

OBJECTIVE: The purpose of this study was to develop a proposed cognitive rehabilitation protocol for post-COVID individuals with cognitive symptoms.

METHODS: A rehabilitation proposed protocol focusing on attention and memory was developed, based on the tests used in the neuropsychological evaluation of affected patients. Researchers held weekly sessions for six months, each lasting 60 minutes. Homework activities were also assigned and corrected in the following session. The attention and memory sessions were conducted with activities based on the applied tests.

RESULTS: Despite the methodological separation of attention and memory, the activities indirectly affect other cognitive functions and abilities, such as executive function, language, reasoning, execution strategies, and cognitive flexibility. A computer, a sheet of paper, and a pen were used to present the slides for the activities. Attention training included all types of attention: sustained, alternating, selective and divided. Memory training sessions included activities that stimulated both short-term and long-term memory. With each session, the difficulty of the activities was gradually increased.

CONCLUSION: Cognitive rehabilitation already has more consolidated evidence about its effectiveness for the treatment of other pathologies, so it can be thought that it will also be a promising strategy for COVID-19 too.}, } @article {pmid38831890, year = {2024}, author = {Zou, XY and Liu, XH and Lu, CL and Jin, XY and He, BX and Liao, YL and Liu, T and Dai, YD and Qi, SH and Sheng, ZJ and Yan, ZF and Yang, GY and Stub, T and Liu, JP}, title = {Traditional Chinese medicine for post-viral olfactory dysfunction: A systematic review.}, journal = {Integrative medicine research}, volume = {13}, number = {2}, pages = {101045}, pmid = {38831890}, issn = {2213-4220}, abstract = {BACKGROUND: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD.

METHODS: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis.

RESULTS: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection).

CONCLUSIONS: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit.

PROTOCOL REGISTRATION: The protocol of this review was registered at PROSPERO: CRD42022366776.}, } @article {pmid38830512, year = {2024}, author = {Blankestijn, JM and Baalbaki, N and Bazdar, S and Beekers, I and Beijers, RJHCG and van den Bergh, JP and Bloemsma, LD and Cornelissen, MEB and Dekker, T and Duitman, JW and Houweling, L and Jacobs, JJL and van der Lee, I and Linders, PMA and Noij, LCE and Nossent, EJ and van de Pol, MA and Sondermeijer, BM and Geelhoed, JJM and Weersink, EJM and Golebski, K and Abdel-Aziz, MI and Maitland-van der Zee, AH and , }, title = {Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response.}, journal = {The Journal of allergy and clinical immunology}, volume = {154}, number = {3}, pages = {807-818}, doi = {10.1016/j.jaci.2024.04.032}, pmid = {38830512}, issn = {1097-6825}, mesh = {Humans ; *COVID-19/immunology/blood ; Male ; Female ; Middle Aged ; *Transcriptome ; *SARS-CoV-2/immunology ; Aged ; *Lung/immunology ; Respiratory Function Tests ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood.

OBJECTIVES: We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease.

METHODS: Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment.

RESULTS: Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV1/forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2.

CONCLUSIONS: This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.}, } @article {pmid38829442, year = {2024}, author = {Finsterer, J}, title = {Post-COVID depression and anxiety are multicausal and not necessarily due to SARS-CoV-2 infection.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {38829442}, issn = {1433-8491}, } @article {pmid38829253, year = {2024}, author = {Julide, T and Cigdem, T and Baris, T}, title = {Cognitive impairment in long-COVID.}, journal = {Ideggyogyaszati szemle}, volume = {77}, number = {5-6}, pages = {151-159}, doi = {10.18071/isz.77.0151}, pmid = {38829253}, issn = {0019-1442}, mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/physiopathology/virology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, abstract = {BACKGROUND AND PURPOSE:

Long Covid is a complex con&shy;dition characterised by symptoms that per&shy;sist for weeks and months after the Co&shy;vid infection, accompanied by cognitive im&shy;pairment that negatively affects daily life. Understanding this complex condition is im&shy;portant for the development of diagnostic and therapeutic strategies.

This article aims to provide a comprehensive overview of cognitive impairment in long-COVID, including its definition, symptoms, pathophysiology, risk factors, assessment tools, imaging abnormalities, potential biomarkers, management strategies, long-term outcomes, and future directions for research.




.

METHODS:

The search methodology used in this review aimed to include a wide range of research on cognitive impairment related to both COVID-19 and long-COVID. Systematic searches of PubMed and Google Scholar databases were conducted using a mixture of MeSH terms and keywords including ‘cognition’, ‘cognitive impairment’, ‘brain fog’, ‘COVID-19’ and ‘long-COVID’. The search was restricted to studies published in English between 1 January 2019 and 11 February 2024, which presented findings on neurological manifestations in human participants.

.

RESULTS:

Long-COVID is characterized by persistent symptoms following COVID-19 infection, with cognitive impairment being a prominent feature. Symptoms include brain fog, difficulties with concentration, memory issues, and executive function deficits. Pa&shy;tho&shy;physiological mechanisms involve vi&shy;ral persistence, immune responses, and vas&shy;cular damage. Risk factors include age, pre-existing conditions, and disease seve&shy;rity. Cognitive assessment tools such as the Montreal Cognitive Assessment (MoCA) are essential for diagnosis. Imaging studies, including MRI, PET, and SPECT, reveal structural and functional brain alterations. Potential biomarkers include C-reactive protein, interleukin-6, and neuron-specific enolase. Management strategies encompass cognitive rehabilitation, occupational therapy, medications, and lifestyle modifications.

.

CONCLUSION:

Long-COVID poses a multifaceted challenge, and cognitive impairment significantly impacts patients’ lives. A multi&shy;disciplinary approach, including cognitive rehabilitation and medication when appropriate, is essential for effective management. Future research should focus on validating biomarkers and understanding long-term cognitive outcomes.

Conclusion &ndash; Long-COVID is a global health concern, and cognitive impairment is a distressing symptom. While pharmacological interventions have potential, they require careful consideration. Continued research is crucial for improving the understanding and treatment of cognitive impairment in long-COVID.

.}, } @article {pmid38829234, year = {2024}, author = {Yee, FTL and Rajagopalan, A and Liang, DTC}, title = {COVID-19: When It Leaves Us Voiceless and Powerless.}, journal = {Psychodynamic psychiatry}, volume = {52}, number = {2}, pages = {173-188}, doi = {10.1521/pdps.2024.52.2.173}, pmid = {38829234}, issn = {2162-2604}, mesh = {Adult ; Female ; Humans ; Middle Aged ; Conversion Disorder/psychology ; *COVID-19/psychology ; COVID-19 Vaccines ; SARS-CoV-2 ; }, abstract = {Conversion disorder-called functional neurological symptom disorder in the DSM-5-has roots that trace back to antiquity. The term conversion, originating from psychoanalysis, signifies the appearance of physical symptoms as an effort to resolve or convey unconscious and distressing intrapsychic conflicts- "converting" them from manifesting in the mind to manifesting in the body. Despite efforts made in elucidating the neurobiological etiologies of functional neurological symptom disorder, a psychodynamic lens remains indispensable in understanding the patient. This article presents two patients who developed functional neurological symptom disorder, one after a COVID-19 vaccination and one in the context of long COVID. A discussion follows on the intrapersonal, interpersonal, and systemic etiological factors that predispose, precipitate, and perpetuate COVID-related functional neurological symptom disorder. We elaborate on psychodynamic psychological processes and conflicts that may unfold between patients with COVID-related functional neurological symptom disorder and their health care providers. We also share suggestions on how a consultation-liaison psychiatry team may offer support to the primary treating team to facilitate a therapeutic space within which patients with COVID-related functional neurological symptom disorder may recover.}, } @article {pmid38828830, year = {2024}, author = {Padmanabhan, P and Roberts, LH and Chancellor, MB and Peters, KM and Zwaans, BMM}, title = {Prospective follow-up of overactive bladder symptoms in patients with prior SARS-CoV-2 infection.}, journal = {Neurourology and urodynamics}, volume = {43}, number = {7}, pages = {1514-1522}, doi = {10.1002/nau.25509}, pmid = {38828830}, issn = {1520-6777}, mesh = {Humans ; *COVID-19/complications/diagnosis ; *Urinary Bladder, Overactive/diagnosis/physiopathology ; Female ; Male ; Middle Aged ; Prospective Studies ; Follow-Up Studies ; Aged ; Adult ; SARS-CoV-2 ; Disease Progression ; }, abstract = {PURPOSE: SARS-CoV-2 infection can result in genitourinary symptoms, such as frequency, urgency, nocturia, and pain/pressure. In this study, we followed the progression of overactive bladder (OAB) symptoms in patients that reported new or worsening OAB symptoms after coronavirus disease-19 (COVID-19) diagnosis.

MATERIALS AND METHODS: Individuals from a COVID-19 serology study were invited to participate in a follow-up study. Respondents were divided into three groups based on prior COVID-19 testing. Patients scored symptoms retrospectively before the pandemic, at study onset, and prospectively during 12-month follow-up. Genitourinary symptoms were assessed using international consultation on incontinence questionaire for OAB (ICIQ-OAB). Change in ICIQ-OAB scores from baseline were calculated. The minimal important difference of one on ICIQ-OAB is considered a significant change.

RESULTS: 26.0% of participants previously had positive COVID polymerase chain reaction (PCR) test (PCR+), 5.6% a positive serology test only (Ser+), and 65.5% were COVID naïve (COVID-). 23.8% of participants reported a significant increase in ICIQ-OAB score at study onset compared to prepandemic. ICIQ-OAB scores were similar at prepandemic but significantly higher at study start (p < 0.001) in PCR+ group. During follow-up, change in ICIQ-OAB scores from baseline remained unchanged for COVID- group, but gradually reduced for PCR+, reaching similar levels as COVID- group by 12 months. By 12 months, 71.4% of PCR+, 42.9% of Ser+, and 68.8% of COVID- participants still reported significant increase in ICIQ-OAB scores.

CONCLUSIONS: Most COVID-19 patients experienced return of symptoms to baseline, indicative of the potential resolution of COVID-associated cystitis. A subset of cases did not, raising questions about the underlying factors contributing to this outcome. Additional research is needed to assess long COVID on urological health.}, } @article {pmid38828796, year = {2024}, author = {Tang, CY and Gao, C and Prasai, K and Li, T and Dash, S and McElroy, JA and Hang, J and Wan, XF}, title = {Prediction models for COVID-19 disease outcomes.}, journal = {Emerging microbes & infections}, volume = {13}, number = {1}, pages = {2361791}, pmid = {38828796}, issn = {2222-1751}, support = {F30 AI172230/AI/NIAID NIH HHS/United States ; T32 LM012410/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/virology ; Male ; Female ; Middle Aged ; Adult ; Retrospective Studies ; *SARS-CoV-2/genetics/isolation & purification ; *Hospitalization/statistics & numerical data ; Cross-Sectional Studies ; Aged ; Missouri/epidemiology ; Young Adult ; Risk Assessment ; Machine Learning ; Adolescent ; }, abstract = {SARS-CoV-2 has caused over 6.9 million deaths and continues to produce lasting health consequences. COVID-19 manifests broadly from no symptoms to death. In a retrospective cross-sectional study, we developed personalized risk assessment models that predict clinical outcomes for individuals with COVID-19 and inform targeted interventions. We sequenced viruses from SARS-CoV-2-positive nasopharyngeal swab samples between July 2020 and July 2022 from 4450 individuals in Missouri and retrieved associated disease courses, clinical history, and urban-rural classification. We integrated this data to develop machine learning-based predictive models to predict hospitalization, ICU admission, and long COVID.The mean age was 38.3 years (standard deviation = 21.4) with 55.2% (N = 2453) females and 44.8% (N = 1994) males (not reported, N = 4). Our analyses revealed a comprehensive set of predictors for each outcome, encompassing human, environment, and virus genome-wide genetic markers. Immunosuppression, cardiovascular disease, older age, cardiac, gastrointestinal, and constitutional symptoms, rural residence, and specific amino acid substitutions were associated with hospitalization. ICU admission was associated with acute respiratory distress syndrome, ventilation, bacterial co-infection, rural residence, and non-wild type SARS-CoV-2 variants. Finally, long COVID was associated with hospital admission, ventilation, and female sex.Overall, we developed risk assessment models that offer the capability to identify patients with COVID-19 necessitating enhanced monitoring or early interventions. Of importance, we demonstrate the value of including key elements of virus, host, and environmental factors to predict patient outcomes, serving as a valuable platform in the field of personalized medicine with the potential for adaptation to other infectious diseases.}, } @article {pmid38827835, year = {2024}, author = {Petrakis, V and Rafailidis, P and Terzi, I and Dragoumani, I and Markatou, F and Papanas, N and Vradelis, S and Gouveri, E and Panopoulou, M and Papazoglou, D and Periklis, P}, title = {The prevalence of long COVID-19 syndrome in hospitalized patients with COVID-19 pneumonia.}, journal = {Le infezioni in medicina}, volume = {32}, number = {2}, pages = {202-212}, pmid = {38827835}, issn = {2532-8689}, abstract = {INTRODUCTION: Long COVID affects millions of individuals worldwide with a wide range of persistent symptoms. Pathogenesis, prevalence and clinical approach of this syndrome remain not well characterized.The aim of the study is the estimation of prevalence of long-COVID and identification of possible risk factors.

PATIENTS AND METHODS: This is an observational prospective study including COVID-19 patients hospitalized at the Department of Infectious Diseases of the University General Hospital of Alexandroupolis (Greece). Eligible COVID-19 patients were interviewed and examined 6, 12 and 18 months after COVID-19 symptoms onset and hospital discharge in order to evaluate the prevalence and consequences of long-COVID symptoms.

RESULTS: A total number of 995 patients were included. The median age at discharge was 55 years and 53% of patients were retired. The majority was males (57%). Vaccination against SARS-CoV-2 was completed in 52% (n=517) COVID-19 patients. More than 40% of COVID-19 patients had at least one symptom at 18 months after hospitalization. Intravenous antiviral 0treatment with remdesivir and complete vaccination status were found to lead to lower rates of Long-COVID.

CONCLUSIONS: More studies in larger patient cohorts are needed in order to identify the underlying biological mechanisms of long-COVID and create effective interventions for prevention and treatment.}, } @article {pmid38827682, year = {2024}, author = {Ranjan, A and Agarwal, R and Mudgal, SK and Bhattacharya, S and Kumar, B}, title = {Young hearts at risk: Unveiling novel factors in myocardial infarction susceptibility and prevention.}, journal = {Journal of family medicine and primary care}, volume = {13}, number = {4}, pages = {1200-1205}, pmid = {38827682}, issn = {2249-4863}, abstract = {The increasing incidence of acute myocardial infarction (AMI) among the young population represents a significant and emerging health concern, contributing substantially to both mortality and morbidity. Unlike myocardial infarctions occurring in older individuals, traditional risk factors such as diabetes and hypertension exhibit a weaker association in the younger demographic. Consequently, there is a pressing need for a deeper understanding of novel risk factors that contribute to AMI in young patients. In this review, we explore distinct risk factor profiles associated with young-onset AMI in comparison to older patients. Special attention is given to novel risk factors, examining their susceptibility factors and exploring preventive measures. The comprehensive risk profile of extremely young South Asians who develop early coronary arterial disease is not yet fully understood. There are many novel evolving risk factors associated with young AMI which need intervention to reduce morbidity and mortality. It has been seen that established inflammatory markers like lipoprotein (a), dyslipidaemia, long COVID, and new emerging risk factors like air pollution (micro- and nanoplastics), periodontitis, acute stress, energy drinks, misuse of recreational drugs may increase risk and influence treatment, and outcomes of AMI in this young population. Screening of emerging novel risk markers and their optimization is important in preventing young patients with AMI. The role of conventional risk factors should not be overlooked and should be treated aggressively. Sex and geographic-specific base approaches are required to reduce risk factors and prevent AMI in young. More prospective studies are needed to evaluate the increasing incidence of young AMI and its associated novel risk factors.}, } @article {pmid38827662, year = {2024}, author = {Mudgal, SK and Patidar, V and Kumar, S and Kumar, S and Gaur, R and Agarwal, R and Varikasuvu, SR and Gupta, P and Varshney, S}, title = {Long-COVID-19 Impact in non-hospitalized patients: Sleep and quality of life 24 months after SARS-CoV-2 infection.}, journal = {Journal of family medicine and primary care}, volume = {13}, number = {4}, pages = {1384-1392}, pmid = {38827662}, issn = {2249-4863}, abstract = {BACKGROUND AND AIMS: Sleep disruption and reduced quality of life are common long coronavirus disease (COVID) manifestations, affecting survivors irrespective of initial COVID-19 severity. Limited research investigates symptoms beyond 24 months post-infection. We aimed to address this gap by longitudinally studying sleep patterns and overall quality of life in non-hospitalized adults, 24 months after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

METHODS: This prospective observational study involved the enrolment of 337 adult non-hospitalized patients in a consecutive fashion. Individuals with past COVID-19 (from 15 April 2020 to 30 June 2021) were examined at two Government hospitals and completed a telephone interview between 1 May 2023 and 30 June 2023, located in Jharkhand, India. Participants were queried about their sleep patterns and quality of life, utilizing the DSM5 LEVEL 2 and EQ-ED-5L tool, respectively.

RESULTS: Among 337 non-hospitalized participants, 212 completed the survey. Within this group (59.4% men, mean age 38), 36 (17.0%) experienced sleep impairment. All five dimensions of quality of life (QoL) were adversely affected in long COVID patients. Advanced age, high income, residing in rural or semi-urban areas, and having comorbidities were associated with a higher likelihood of decreased quality of life across various domains. Conversely, participants who were married, employed in healthcare or government positions, and vaccinated exhibited a reduced likelihood of experiencing lower quality of life.

CONCLUSION: Long COVID-19 affects sleep and quality of life, with various demographic and clinical factors influencing outcomes. This study provides insights into the extended consequences of long COVID-19 and aids healthcare systems in addressing the challenges posed by this condition.}, } @article {pmid38827576, year = {2024}, author = {Liviero, F and Scapellato, ML and Volpin, A and Battistella, M and Fabris, L and Brischigliaro, L and Folino, F and Moretto, A and Mason, P and Pavanello, S}, title = {Long term follow-up of heart rate variability in healthcare workers with mild COVID-19.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1403551}, pmid = {38827576}, issn = {1664-2295}, abstract = {INTRODUCTION: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available.

METHODS: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded.

RESULTS: Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, n = 17), 13 months (subgroup-B, n = 37) and both at 6 and 13 months (subgroup-C, n = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) (t = 2.99, p = 0.009), a decrease in the normalized low frequency power (nLF) (t = 2.98, p = 0.009) and in the LF/HF ratio (t = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF (t = 2.54, p = 0.02); a decrease in nLF (t = 2.62, p = 0.01) and in the LF/HF ratio (t = 4.00, p = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively); lower in nLF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively), and in LF/HF (t = 1.92, p = 0.08 and (t = 2.43, p = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF (t = 2.19, p = 0.04); an increase in nLF (t = 2.15, p = 0.04) and in LF/HF (t = 3.49, p = 0.002).

CONCLUSION: These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.}, } @article {pmid38826995, year = {2024}, author = {Prusinski, C and Yan, D and Klasova, J and McVeigh, KH and Shah, SZ and Fermo, OP and Kubrova, E and Farr, EM and Williams, LC and Gerardo-Manrique, G and Bergquist, TF and Pham, SM and Engelberg-Cook, E and Hare, JM and March, KL and Caplan, AI and Qu, W}, title = {Multidisciplinary Management Strategies for Long COVID: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e59478}, pmid = {38826995}, issn = {2168-8184}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions.}, } @article {pmid38826986, year = {2024}, author = {Ono, R and Takayama, S and Abe, M and Arita, R and Abe, T and Ishii, T}, title = {Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e59433}, pmid = {38826986}, issn = {2168-8184}, abstract = {Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVID biomarkers in non-hospitalized patients. Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers. The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.}, } @article {pmid38826460, year = {2024}, author = {Botdorf, M and Dickinson, K and Lorman, V and Razzaghi, H and Marchesani, N and Rao, S and Rogerson, C and Higginbotham, M and Mejias, A and Salyakina, D and Thacker, D and Dandachi, D and Christakis, DA and Taylor, E and Schwenk, H and Morizono, H and Cogen, J and Pajor, NM and Jhaveri, R and Forrest, CB and Bailey, LC}, title = {EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38826460}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {OBJECTIVE: Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better.

METHODS: The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences.

RESULTS: The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74).

CONCLUSIONS: Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.}, } @article {pmid38825753, year = {2024}, author = {Reiersen, AM and Zorumski, CF and Lenze, EJ}, title = {Fluvoxamine and long COVID: Post-acute recovery.}, journal = {Reviews in medical virology}, volume = {34}, number = {4}, pages = {e2557}, doi = {10.1002/rmv.2557}, pmid = {38825753}, issn = {1099-1654}, support = {//Center for Brain Research in Mood Disorders at Washington University/ ; //The Bantly Foundation/ ; UL1TR002345/NH/NIH HHS/United States ; //COVID-19 Early Treatment Fund/ ; //Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine in St. Louis/ ; //Washington University Institute of Clinical and Translational Sciences/ ; UL1 TR002345/TR/NCATS NIH HHS/United States ; //Cures Within Reach/ ; //Mercatus Fast Grants/ ; }, mesh = {Humans ; *COVID-19 Drug Treatment ; *Fluvoxamine/therapeutic use ; *COVID-19/virology ; *SARS-CoV-2/drug effects ; Post-Acute COVID-19 Syndrome ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; }, } @article {pmid38825094, year = {2024}, author = {Piamonti, D and Panza, L and Flore, R and Baccolini, V and Pellegrino, D and Sanna, A and Lecci, A and Lo Muzio, G and Angelone, D and Mirabelli, FM and Morviducci, M and Onorati, P and Messina, E and Panebianco, V and Catalano, C and Bonini, M and Palange, P}, title = {Ventilatory efficiency in long-term dyspnoeic patients following COVID-19 pneumonia.}, journal = {Respiratory physiology & neurobiology}, volume = {327}, number = {}, pages = {104285}, doi = {10.1016/j.resp.2024.104285}, pmid = {38825094}, issn = {1878-1519}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; *Dyspnea/physiopathology/etiology ; Female ; Middle Aged ; Aged ; Exercise Test ; Tomography, X-Ray Computed ; Respiratory Function Tests ; Prospective Studies ; Lung/physiopathology/diagnostic imaging ; Spirometry ; SARS-CoV-2 ; Pulmonary Ventilation/physiology ; }, abstract = {BACKGROUND: Long COVID is defined as persistency of symptoms, such as exertional dyspnea, twelve weeks after recovery from SARS-CoV-2 infection.

OBJECTIVES: To investigate ventilatory efficiency by the use of cardiopulmonary exercise testing (CPET) in patients with exertional dyspnea despite normal basal spirometry after 18 (T18) and 36 months (T36) from COVID-19 pneumonia.

METHODS: One hundred patients with moderate-critical COVID-19 were prospectively enrolled in our Long COVID program. Medical history, physical examination and lung high-resolution computed tomography (HRCT) were obtained at hospitalization (T0), 3 (T3) and 15 months (T15). All HRCTs were revised using a semi-quantitative CT severity score (CSS). Pulmonary function tests were obtained at T3 and T15. CPET was performed in a subset of patients with residual dyspnea (mMRC ≥ 1), at T18 and at T36.

RESULTS: Remarkably, at CPET, ventilatory efficiency was reduced both at T18 (V'E/V'CO2 slope = 31.4±3.9 SD) and T36 (V'E/V'CO2 slope = 31.28±3.70 SD). Furthermore, we identified positive correlations between V'E/V'CO2 slope at T18 and T36 and both percentage of involvement and CSS at HRCT at T0, T3 and T15. Also, negative linear correlations were found between V'E/V'CO2 slope at T18 and T36 and DLCO at T3 and T15.

CONCLUSIONS: At eighteen months from COVID-19 pneumonia, 20 % of subjects still complains of exertional dyspnea. At CPET this may be explained by persistently reduced ventilatory efficiency, possibly related to the degree of lung parenchymal involvement in the acute phase of infection, likely reflecting a damage in the pulmonary circulation.}, } @article {pmid38825071, year = {2024}, author = {Martínez-Fleta, P and Marcos, MC and Jimenez-Carretero, D and Galván-Román, JM and Girón-Moreno, RM and Calero-García, AA and Arcos-García, A and Martín-Gayo, E and de la Fuente, H and Esparcia-Pinedo, L and Aspa, J and Ancochea, J and Alfranca, A and Sánchez-Madrid, F}, title = {Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {264}, number = {}, pages = {110267}, doi = {10.1016/j.clim.2024.110267}, pmid = {38825071}, issn = {1521-7035}, mesh = {Humans ; *Receptors, CCR6/immunology/metabolism ; *CD8-Positive T-Lymphocytes/immunology ; *COVID-19/immunology ; *CD4-Positive T-Lymphocytes/immunology ; *Receptors, CXCR3/immunology/metabolism ; *SARS-CoV-2/immunology ; *Interferon-gamma/immunology/metabolism ; Male ; Female ; Middle Aged ; Aged ; Adult ; }, abstract = {Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4[+] cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8[+] T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6[+] CD4[+] subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6[+] CD4[+] are decreased in LC patients, whereas CXCR3[+] CCR6[-] and CCR4[+] CCR6[-] CD4[+] T cells are increased. LC patients showed lower IFN-γ-secreting CD8[+] T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.}, } @article {pmid38824899, year = {2024}, author = {Lai, CY and Lin, CH and Chao, TC and Lin, CH and Chang, CC and Huang, CY and Chiang, SL}, title = {Effectiveness of a 12-week telerehabilitation training in people with long COVID: A randomized controlled trial.}, journal = {Annals of physical and rehabilitation medicine}, volume = {67}, number = {5}, pages = {101853}, doi = {10.1016/j.rehab.2024.101853}, pmid = {38824899}, issn = {1877-0665}, mesh = {Humans ; *Telerehabilitation ; Male ; Female ; *COVID-19/rehabilitation ; Middle Aged ; *Quality of Life ; *Self Efficacy ; Aged ; *Cardiorespiratory Fitness ; Exercise Therapy/methods ; Sleep Quality ; Exercise ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {BACKGROUND: Telerehabilitation has been developed and applied for years for cardiac and pulmonary diseases with good clinical outcomes. However, its application to participants with long COVID remains limited.

OBJECTIVES: To investigate the effectiveness of a 12-week telerehabilitation training program in participants with long COVID. The primary outcome was cardiorespiratory fitness (CRF), and secondary outcomes were physical activity (PA) amounts, exercise self-efficacy, sleep quality, and health-related quality of life (HRQOL).

METHODS: A parallel-group, randomized controlled trial was conducted. Eligible participants with long COVID (n = 182) were randomly assigned in a 1:1 ratio to either the experimental group (EG) or the control group (CG). The EG received 12 weeks of telerehabilitation training with weekly remote monitoring for exercise maintenance and support. The CG received PA counseling only. CRF, PA amounts, exercise self-efficacy, sleep quality, and HRQOL were assessed at baseline and 12 weeks. Generalized estimating equations were used to analyze the intervention effects by examining the interaction between time and group.

RESULTS: One hundred twenty-two participants (67 %) completed the study, and 182 were included in the intention-to-treat analysis. The EG had greater walking behavior (β = -763.3, p < 0.001), total amount of PA (β= -711, p = 0.003), exercise self-efficacy (β = -1.19, p < 0.001), and better sleep quality (β = 1.69, p = 0.012) after the 12-weeks of telerehabilitation training than the CG. However, there were no significant differences in any CRF parameters or HRQOL at 12 weeks between the EG and CG.

CONCLUSION: Telerehabilitation training offers a personalized and convenient approach that can increase exercise willingness and PA amounts and improve sleep quality. These findings underscore the potential benefits of telerehabilitation training for promoting healthier lifestyles and improving overall health outcomes.

CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05205460) on January 25, 2022.}, } @article {pmid38822405, year = {2024}, author = {Fang, LC and Ming, XP and Cai, WY and Hu, YF and Hao, B and Wu, JH and Tuohuti, A and Chen, X}, title = {Development and validation of a prognostic model for assessing long COVID risk following Omicron wave-a large population-based cohort study.}, journal = {Virology journal}, volume = {21}, number = {1}, pages = {123}, pmid = {38822405}, issn = {1743-422X}, support = {82071033//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; Prognosis ; Risk Factors ; Cohort Studies ; Aged ; *Nomograms ; Adult ; Hospitalization/statistics & numerical data ; Risk Assessment ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model.

METHODS: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4-8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA).

RESULTS: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort.

CONCLUSIONS: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID.}, } @article {pmid38822168, year = {2024}, author = {Grutman, AJ and Gilliam, K and Maremanda, AP and Able, C and Choi, U and Alshak, MN and Kohn, TP}, title = {Comparing risk of post infection erectile dysfunction following SARS Coronavirus 2 stratified by acute and long COVID, hospitalization status, and vasopressor administration: a U.S. large claims database analysis.}, journal = {International journal of impotence research}, volume = {}, number = {}, pages = {}, pmid = {38822168}, issn = {1476-5489}, abstract = {No study has yet assessed the risk of developing erectile dysfunction (ED) after a diagnosis of long COVID, defined by the Centers for Disease Control and Prevention as the persistence or presence of new symptoms at least 4 weeks after initial SARS-CoV-2 infection, when compared to those diagnosed with acute COVID or cases in which more severe treatment is required. To assess these risks, we queried the TriNetX COVID-19 Research Network from December 1st 2020 through June 2023. Men aged ≥ 18 diagnosed with long COVID were compared to those diagnosed with acute COVID and analyses were performed to compare men who were/were not hospitalized within 1 month of acute COVID diagnosis and men who did/did not need vasopressors. Cohorts were propensity score matched and compared for differences in new ED diagnosis and/or prescription of phosphodiesterase-5 inhibitors (PDE5i). After propensity score matching, the long and acute COVID cohorts included 2839 men with an average age of 54.5±16.7 and 55.1±17.1 years respectively (p = 0.21). Men with long COVID were more likely to develop ED or be prescribed PDE5i (3.63%) when compared to men with only acute COVID infections (2.61%) [RR 1.39; 95% CI 1.04, 1.87]. There was no statistically significant risk of developing ED or being prescribed PDE5i for individuals who received vasopressors [RR 0.92; 95% CI 0.77,1.10] or were hospitalized [RR 0.93; 95% CI 0.82,1.06].}, } @article {pmid38820895, year = {2024}, author = {Obeid, DA and Al-Qahtani, AA and Almaghrabi, RS and Alahideb, BM and Alharbi, LA and AlAbdulkareem, MA and Almadi, TM and Alsanea, MS and Althawadi, SI and Altamimi, SA and Alhamlan, FS}, title = {Characteristics and clinical manifestations of patients, including organ transplant patients, during the surge of JN.1: Insights from Saudi Arabia.}, journal = {Journal of infection and public health}, volume = {17}, number = {7}, pages = {102452}, doi = {10.1016/j.jiph.2024.05.040}, pmid = {38820895}, issn = {1876-035X}, mesh = {Humans ; Saudi Arabia/epidemiology ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; Adult ; Aged ; *SARS-CoV-2/genetics ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Aged, 80 and over ; *Transplant Recipients/statistics & numerical data ; *Organ Transplantation/adverse effects ; Risk Factors ; }, abstract = {BACKGROUND: Amidst the persistent global health threat posed by the evolving SARS-CoV-2 virus throughout the four-year-long COVID-19 pandemic, the focus has now turned to the Omicron variant and its subvariant, JN.1, which has rapidly disseminated worldwide. This study reports on the characteristics and clinical manifestations of patients during the surge of the JN.1 variant in Saudi Arabia; it also investigates the evolution of SARS-CoV-2 variants in organ transplant patients and identifies patient risk factors.

METHODS: A total of 151 nasopharyngeal samples from patients with PCR-confirmed SARS-CoV-2 infection were collected between September 2023 and January 2024. Demographic and clinical data of the patients were obtained from electronic health records. All confirmed positive samples underwent sequencing using Ion GeneStudio and the Ion AmpliSeq™ SARS-CoV-2 panel.

RESULTS: During the surge of the JN.1 variant, the average age of the patients was 40 years, ranging from 3 to 93 years, and nearly 50% of the patients were male. Our investigation revealed that the J.N variant predominantly infected patients with comorbidities or organ transplant recipients (57.6%). Moreover, patients with comorbidities or organ transplants exhibited a higher number of mutations. In our organ transplant cohort, an increased total number of spike mutations was associated with a lower risk of developing severe disease (OR = 0.96, 95% CI: 0.93-0.98).

CONCLUSIONS: Although JN.1 may not prove to be particularly harmful, it is crucial to recognize the persistent emergence of concerning variants, which create new pathways for the virus to evolve. The ongoing evolution of SARS-CoV-2 is evident in the continuous divergence of these variants from the original strain that marked the onset of the pandemic nearly four years ago.}, } @article {pmid38819890, year = {2024}, author = {Dalko, K and Elsuson, HA and Kalter, I and Zilezinski, M and Hofstetter, S and Stoevesandt, D and Paulicke, D and Jahn, P}, title = {Virtual Reality Applications for the Implementation of Domestic Respiratory Rehabilitation Programs for Patients With Long COVID and Post-COVID Condition: Scoping Review.}, journal = {JMIR serious games}, volume = {12}, number = {}, pages = {e52309}, pmid = {38819890}, issn = {2291-9279}, abstract = {BACKGROUND: Due to a high number of patients affected by long COVID or post-COVID condition, an essential step to address the long-term effects of COVID-19 lies in the development and implementation of flexible and accessible rehabilitation programs. Virtual reality (VR) technologies offer the potential to support traditional therapies with individualized at-home programs.

OBJECTIVE: This study aims to provide an overview of existing scientific evidence on the development and implementation of VR-assisted respiratory rehabilitation programs for patients with long COVID and post-COVID condition and to synthesize the results.

METHODS: We conducted a scoping review of studies from 6 databases. PubMed, CINAHL, Cochrane, ScienceDirect, Web of Science Social Sciences Citation Index, and PEDro were searched using an exploratory search strategy. The search, which was last updated in February 2024, included peer-reviewed studies on immersive VR applications providing respiratory rehabilitation programs for patients with chronic obstructive pulmonary disease and long COVID or post-COVID condition. Exclusion criteria were studies in clinical or inpatient settings, telemedicine, nonimmersive VR applications, and gray literature. Nine publications were included in this review. Findings were extracted and summarized from the studies according to the JBI (Joanna Briggs Institute) method and thematically categorized. Topics covered were study characteristics, physiotherapeutic concept, clinical parameters, as well as usability and acceptability.

RESULTS: The 9 publications included in the qualitative analysis were published in 2019-2023. Eight empirical studies were included: 4 followed a mixed methods design, 3 were qualitative studies, and 1 followed a quantitative method. One scoping review was included in the data analyses. Four of the included studies were on patients with chronic obstructive pulmonary disease. The 9 studies demonstrated that VR-supported respiratory rehabilitation programs result in positive initial outcomes in terms of physical as well as psychological parameters. Particularly noteworthy was the increased motivation and compliance of patients. However, adverse effects and lack of usability are the barriers to the implementation of this innovative approach.

CONCLUSIONS: Overall, VR is a promising technology for the implementation of individualized and flexible respiratory rehabilitation programs for patients with long COVID and post-COVID condition. Nevertheless, corresponding approaches are still under development and need to be more closely adapted to the needs of users. Further, the evidence was limited to pilot studies or a small number of patients, and no randomized controlled trials or long-term studies were part of the study selection. The included studies were performed by 4 groups of researchers: 3 from Europe and 1 from the United States.}, } @article {pmid38819528, year = {2024}, author = {Oguz-Akarsu, E and Gullu, G and Kilic, E and Dinç, Y and Akdag, G and Rehber, C and Karli, N}, title = {Beyond the acute: pain in long COVID survivors at 1.5 years.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {9}, pages = {4109-4117}, pmid = {38819528}, issn = {1590-3478}, mesh = {Humans ; *COVID-19/complications ; Female ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Headache/epidemiology/etiology ; Adult ; Myalgia/etiology/physiopathology ; Aged ; Survivors ; Neuralgia/etiology ; SARS-CoV-2 ; Cohort Studies ; Follow-Up Studies ; }, abstract = {OBJECTIVE: Long COVID, characterized by persistent symptoms post-acute COVID-19, remains a subject of intense investigation. This study focuses on pain, a common and notable symptom reported by long COVID patients.

METHOD: A cohort of 191 individuals, initially diagnosed with mild-to-moderate COVID-19, was followed up 1.5 years later to assess the frequency, clinical characteristics, and factors associated with pain persistence.

RESULTS: Our study revealed that 31.9% of participants experienced at least one persistent pain symptom after 1.5 years. Headache emerged as the most prevalent symptom (29.8%), followed by myalgia (5.8%) and neuropathic pain (4.2%). Factors such as female gender and the presence of neuropathic pain symptom were identified as predictors of long-term headaches. Myalgia, showed associations with headache, arthralgia, and low ferritin levels. Persistent neuropathic pain symptom (4.2%) was linked to older age, female gender, sore throat, and headache.

CONCLUSION: This study provides insights into the evolution of pain symptoms over time after COVID-19 infection, emphasizing the interconnection between different pain syndromes. This research contributes to understanding the diverse and evolving nature of pain in long COVID survivors, offering valuable insights for targeted interventions and further investigations into the underlying mechanisms of persistent pain.}, } @article {pmid38818469, year = {2024}, author = {Li, J and Huang, Q and Liang, Y and Jiang, J and Yang, Y and Feng, J and Tan, X and Li, T}, title = {The Potential Mechanisms of Arrhythmia in Coronavirus disease-2019.}, journal = {International journal of medical sciences}, volume = {21}, number = {7}, pages = {1366-1377}, pmid = {38818469}, issn = {1449-1907}, mesh = {Humans ; *COVID-19/complications/immunology/virology ; *Arrhythmias, Cardiac/etiology/virology/physiopathology ; *SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) leads to coronavirus disease-2019 (COVID-19) which can cause severe cardiovascular complications including myocardial injury, arrhythmias, acute coronary syndrome and others. Among these complications, arrhythmias are considered serious and life-threatening. Although arrhythmias have been associated with factors such as direct virus invasion leading to myocardial injury, myocarditis, immune response disorder, cytokine storms, myocardial ischemia/hypoxia, electrolyte abnormalities, intravascular volume imbalances, drug interactions, side effects of COVID-19 vaccines and autonomic nervous system dysfunction, the exact mechanisms of arrhythmic complications in patients with COVID-19 are complex and not well understood. In the present review, the literature was extensively searched to investigate the potential mechanisms of arrhythmias in patients with COVID-19. The aim of the current review is to provide clinicians with a comprehensive foundation for the prevention and treatment of arrhythmias associated with long COVID-19.}, } @article {pmid38818142, year = {2024}, author = {Aghaei, A and Qiao, S and Chi Tam, C and Yuan, G and Li, X}, title = {Role of self-esteem and personal mastery on the association between social support and resilience among COVID-19 long haulers.}, journal = {Heliyon}, volume = {10}, number = {10}, pages = {e31328}, pmid = {38818142}, issn = {2405-8440}, abstract = {Although the COVID-19 mortality rate is declining, the number of individuals dealing with persistent COVID-19 symptoms is increasing worldwide, making long COVID a global public health concern. People with long COVID (long haulers) often deal with physical and mental stressors. Long haulers' psychological resilience could play a key role in coping with these stressors in intercorrelation with psychosocial resources. The current study aims to test a hypothesized relationship between social support and its functions (i.e., instrumental and emotional) and the resilience of long haulers through serial mediation by personal mastery and self-esteem. A cross-sectional and self-administered online survey was conducted among 460 individuals with long COVID recruited from COVID-19 Facebook support groups in the United States. Analyzing data indicated a positive correlation between social support and the resilience of long haulers. Structural equation modeling suggested that self-esteem and personal mastery fully mediated the association between social (instrumental) support and resilience. Personal mastery also mediated the association between self-esteem and resilience in social (instrumental) support models. However, in the emotional support model, the indirect effect was non-significant for the mediation by personal mastery and self-esteem. Findings suggest that social support, mainly instrumental support, may protect long haulers by promoting their resilience through self-esteem and personal mastery. This study emphasizes the importance of including social support services in designing programs for COVID-19 long haulers.}, } @article {pmid38816726, year = {2024}, author = {Haslam, A and Prasad, V}, title = {Long COVID clinics and services offered by top US hospitals: an empirical analysis of clinical options as of May 2023.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {684}, pmid = {38816726}, issn = {1472-6963}, mesh = {Humans ; *COVID-19/therapy/epidemiology ; United States ; Cross-Sectional Studies ; *SARS-CoV-2 ; Hospitals/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Referral and Consultation/statistics & numerical data ; }, abstract = {BACKGROUND: The economic and health burden of COVID-19 has transformed the healthcare system in the US. Hospitals have adapted to the heterogeneity in long COVID symptoms, and the sheer number of people affected by this condition, by building long COVID centers and programs.

OBJECTIVE: We sought to describe characteristics, services, and clinical trials of long COVID centers at top US hospitals.

DESIGN: Cross-sectional analysis.

PARTICIPANTS: Long COVID treatment programs or centers at top US hospitals.

EXPOSURES: Frequency of long COVID centers, eligibility for being treated, the services they provide, specialist to whom the patients may be referred, and the long COVID clinical trials in which these hospitals participate.

FINDINGS: Most top hospitals in the US (n = 43/50; 86%) offer long COVID services. 65% (28/43) did not describe the services provided. 12 (28%) required a referral from a primary care physician. The most common services were meeting with a team member (n = 20; 47%), ordering lab and/or radiology services (n = 8; 18.6%), and administering a physical exam (n = 7; 16%). 7 (16%) centers/programs treated only adults; 5 (12%) treated both adults and children, and 31 (72%) did not specify. The most common specialists described were psychology (n = 25; 58%), neurology (n = 25; 58%), and pulmonary (n = 24; 56%). Sixty-three trials (of 134 long COVID clinical trials) had at least one top hospital listed as a study site. The median number of clinical trials that each hospital sponsored or was a study site was 2 (interquartile range: 1, 3).

CONCLUSIONS AND RELEVANCE: We find that services offered at long COVID clinics at top hospitals in the US often include meeting with a team member and referrals to a wide range of specialists. The diversity in long COVID services offered parallels the diversity in long COVID symptoms, suggesting a need for better consensus in developing and delivering treatment.}, } @article {pmid38816335, year = {2025}, author = {Mclaughlin, M and Cerexhe, L and Macdonald, E and Ingram, J and Sanal-Hayes, NEM and Meach, R and Carless, D and Sculthorpe, N}, title = {Erratum to A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long-COVID in Scotland: Part I.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {155}, doi = {10.1016/j.amjmed.2024.02.024}, pmid = {38816335}, issn = {1555-7162}, } @article {pmid38816141, year = {2024}, author = {Salgado, M and Gálvez, C and Nijhuis, M and Kwon, M and Cardozo-Ojeda, EF and Badiola, J and Gorman, MJ and Huyveneers, LEP and Urrea, V and Bandera, A and Jensen, BO and Vandekerckhove, L and Jurado, M and Raj, K and Schulze Zur Wiesch, J and Bailén, R and Eberhard, JM and Nabergoj, M and Hütter, G and Saldaña-Moreno, R and Oldford, S and Barrett, L and Ramirez, MLM and Garba, S and Gupta, RK and Revollo, B and Ferra-Coll, C and Kuball, J and Alter, G and Sáez-Cirión, A and Diez-Martin, JL and Duke, ER and Schiffer, JT and Wensing, A and Martinez-Picado, J and , }, title = {Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.}, journal = {The lancet. HIV}, volume = {11}, number = {6}, pages = {e389-e405}, pmid = {38816141}, issn = {2352-3018}, support = {P01 AI178376/AI/NIAID NIH HHS/United States ; UM1 AI164561/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *HIV Infections/immunology/virology ; Male ; Prospective Studies ; Female ; Adult ; Middle Aged ; HIV-1/immunology ; Transplantation, Homologous ; Biomarkers/blood ; Viral Load ; HIV Antibodies/blood ; }, abstract = {BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT.

METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT.

FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months).

INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT.

FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.}, } @article {pmid38815619, year = {2025}, author = {Oh, J and Kang, J and Yon, DK}, title = {Editorial: Mental Health Distress in Long COVID Condition Among the Pediatric Population: A Contemporary Medical Challenge.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {64}, number = {1}, pages = {27-29}, doi = {10.1016/j.jaac.2024.05.019}, pmid = {38815619}, issn = {1527-5418}, mesh = {Humans ; *COVID-19/psychology ; Child ; *Post-Acute COVID-19 Syndrome ; Adolescent ; SARS-CoV-2 ; Mental Disorders/epidemiology ; }, abstract = {As the coronavirus disease of 2019 (COVID-19) pandemic continues, a body of emerging evidence suggests that individuals who had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suffered from lingering adverse health consequences. Such long-term conditions, also known as "long COVID" or "post-acute COVID syndrome," are reported to bring both pulmonary and extrapulmonary manifestations.[1] The most common features of long COVID include fatigue and headache, which frequently occur with neuropsychiatric impairments. Given that the onset of mental disorders occurs primarily in late childhood and adolescence, it is essential to focus on the pediatric population to determine the risk of mental disorder diagnosis following SARS-CoV-2 infection.}, } @article {pmid38814888, year = {2024}, author = {Rahman, A and Russell, M and Zheng, W and Eckrich, D and Ahmed, I and , }, title = {SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C).}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0295891}, pmid = {38814888}, issn = {1932-6203}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Schizophrenia/epidemiology/diagnosis ; Male ; *Psychotic Disorders/epidemiology/diagnosis ; Female ; Adult ; Middle Aged ; Cohort Studies ; *SARS-CoV-2/isolation & purification ; United States/epidemiology ; Respiratory Distress Syndrome/epidemiology ; Aged ; Young Adult ; }, abstract = {Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.}, } @article {pmid38814744, year = {2024}, author = {Schröder, J and Dinse, H and Maria Jahre, L and Skoda, EM and Stettner, M and Kleinschnitz, C and Teufel, M and Bäuerle, A}, title = {Needs and Demands for e-Health Symptom Management Interventions in Patients with Post-COVID-19 Condition: A User-Centered Design Approach.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {30}, number = {8}, pages = {2194-2202}, doi = {10.1089/tmj.2024.0088}, pmid = {38814744}, issn = {1556-3669}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Telemedicine/organization & administration ; Middle Aged ; Adult ; *SARS-CoV-2 ; User-Centered Design ; Aged ; Surveys and Questionnaires ; Young Adult ; Smartphone ; Needs Assessment ; }, abstract = {Introduction: Post-COVID-19 is an increasing chronic disease for which potential treatment options require further development and examination. A well-established approach to symptom management in post-COVID-19 patients could be e-Health interventions. To enhance the implementation and utilization of e-Health interventions, the needs and demands of patients should be taken into consideration. The aim of this study was to investigate needs and demands of post-COVID-19 patients concerning e-Health symptom management interventions. Methods: A total of 556 patients participated in this cross-sectional online survey study. Recruitment was performed from January 19 to May 24, 2022. Data related to the needs and demands for e-Health interventions were analyzed, along with medical and sociodemographic information. Results: The majority of the patients preferred interventions accessible on smartphones (95.3%). The favored content formats were applications (82.7%), interactive training (69.3%), or audio and video materials (61.1%). Furthermore, the preferred session length was about 10-20 min. The most desired topics included "quality of life," "information about how intensively I may exert myself or do sports," "adjustment to new life situation," and "handling physical changes." Conclusions: This study provides a detailed framework for the content and design of e-Health interventions to support patients managing their post-COVID-19 symptoms. The findings could significantly influence the further development of tailored e-Health interventions to address this pressing global health concern.}, } @article {pmid38813984, year = {2024}, author = {Hurt, RT and Yadav, S and Schroeder, DR and Croghan, IT and Mueller, MR and Grach, SL and Aakre, CA and Gilman, EA and Stephenson, CR and Overgaard, J and Collins, NM and Lawson, DK and Thompson, AM and Natividad, LT and Mohamed Elfadil, O and Ganesh, R}, title = {Longitudinal Progression of Patients with Long COVID Treated in a Post-COVID Clinic: A Cross-Sectional Survey.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241258671}, pmid = {38813984}, issn = {2150-1327}, mesh = {Humans ; Cross-Sectional Studies ; *COVID-19/therapy ; Middle Aged ; Female ; Male ; *Post-Acute COVID-19 Syndrome ; Adult ; Surveys and Questionnaires ; Longitudinal Studies ; Disease Progression ; SARS-CoV-2 ; Aged ; }, abstract = {BACKGROUND: In addition to the morbidity and mortality associated with acute infection, COVID-19 has been associated with persistent symptoms (>30 days), often referred to as Long COVID (LC). LC symptoms often cluster into phenotypes, resembling conditions such as fibromyalgia, postural orthostatic tachycardiac syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). LC clinics have been established to best address the needs of LC patients and continuity of care. We developed a cross-sectional survey to assess treatment response through our LC Clinic (LCC).

METHODS: A 25-question survey (1-10 Likert scale) was expert- and content-validated by LCC clinicians, patients, and patient advocates. The survey assessed LC symptoms and the helpfulness of different interventions, including medications and supplements. A total of 852 LCC patients were asked to complete the survey, with 536 (62.9%) responding.

RESULTS: The mean time from associated COVID-19 infection to survey completion was 23.2 ± 6.4 months. The mean age of responders was 52.3 ± 14.1 (63% females). Self-reported symptoms were all significantly improved (P < .001) from the initial visit to the LCC (baseline) to the time of the follow-up survey. However, only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey, indicating low levels of full recovery in our cohort. The patients rated numerous interventions as being helpful, including low-dose naltrexone (45/77; 58%), vagal nerve stimulation (18/34; 53%), and fisetin (28/44; 64%).

CONCLUSIONS: Patients report general improvements in symptoms following the initial LCC visit, but complete recovery rates remain low at 23.2 ± 6.4 months.}, } @article {pmid38813452, year = {2024}, author = {Chopra, H and Furnish, T and Verduzco-Gutierrez, M and Jevotovsky, DS and Castellanos, J}, title = {Long-COVID symptoms improved after MDMA and psilocybin therapy: A case report.}, journal = {Clinical case reports}, volume = {12}, number = {6}, pages = {e8791}, pmid = {38813452}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: Long-COVID syndrome lacks effective holistic treatment options. We present a case of a 41-year-old fully vaccinated female with Long-COVID syndrome who obtained significant symptomatic relief after self-medicating with psilocybin and MDMA.

ABSTRACT: Long-COVID, a syndrome persisting after the acute phase of coronavirus disease 2019 (COVID-19), lacks effective holistic treatment options. We present a case of a 41-year-old fully vaccinated female with Long-COVID syndrome who obtained significant symptomatic relief by self-prescribing psilocybin and MDMA. Future research is needed to assess safety and efficacy.}, } @article {pmid38813442, year = {2024}, author = {Heald, AH and Williams, R and Jenkins, DA and Stewart, S and Bakerly, ND and Mccay, K and Ollier, W}, title = {The prevalence of long COVID in people with diabetes mellitus-evidence from a UK cohort.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102607}, pmid = {38813442}, issn = {2589-5370}, abstract = {BACKGROUND: It was apparent from the early phase of the SARS-CoV-2 virus (COVID-19) pandemic that a multi-system syndrome can develop in the weeks following a COVID-19 infection, now referred to as Long COVID. Given that people living with diabetes are at increased risk of hospital admission/poor outcomes following COVID-19 infection we hypothesised that they may also be more susceptible to developing Long COVID. We describe here the prevalence of Long COVID in people living with diabetes when compared to matched controls in a Northwest UK population.

METHODS: This was a retrospective cohort study of people who had a recorded diagnosis of type 1 diabetes (T1D) or type 2 diabetes (T2D) who were alive on 1st January 2020 and who had a proven COVID-19 infection. We used electronic health record data from the Greater Manchester Care Record collected from 1st January 2020 to 16th September 2023, we determined the prevalence of Long COVID in people with T1D and T2D vs matched individuals without diabetes (non-DM).

FINDINGS: There were 3087 T1D individuals with 14,077 non-diabetes controls and 3087 T2D individuals with 14,077 non-diabetes controls and 29,700 T2D individuals vs 119,951 controls. For T1D, there was a lower proportion of Long COVID diagnosis and/or referral to a Long COVID service at 0.33% vs 0.48% for matched controls. The prevalence of Long COVID In T2D individuals was 0.53% vs 1:3 matched controls 0.54%. For T2D, there were differences by sex in the prevalence of Long COVID in comparison with 1:3 matched controls. For Long COVID between males with T2D and their matched controls, the prevalence was lower in matched controls at 0.46%.vs 0.54% (0.008). When considering the prevalence of LC between females with T2D and their matched controls, the prevalence was higher in matched controls at 0.61% vs 0.53% (0.007). The prevalence of Long COVID in males with T2D vs females was not different. T2D patients at older vs younger age were at reduced risk of developing Long COVID (OR 0.994 [95% CI) [0.989, 0.999]). For females there was a minor increase of risk (OR 1.179, 95% CI [1.002, 1.387]). Presence of a higher body mass index (BMI) was also associated an increased risk of developing Long COVID (OR 1.013, 95% CI [1.001, 1.026]). The estimated general population prevalence of Long COVID based on general practice coding (not self-reported) of this diagnosis was 0.5% of people with a prior acute COVID-19 diagnosis.

INTERPRETATION: Recorded Long COVID was more prevalent in men with T2D than in matched non-T2D controls with the opposite seen for T2D women, with recorded Long COVID rates being similar for T2D men and women. Younger age, female sex and higher BMI were all associated with a greater likelihood of developing Long COVID when taken as individual variables. There remains an imperative for continuing awareness of Long COVID as a differential diagnosis for multi-system symptomatic presentation in the context of a previous acute COVID-19 infection.

FUNDING: The time of co-author RW was supported by the NIHR Applied Research Collaboration Greater Manchester (NIHR200174) and the NIHR Manchester Biomedical Research Centre (NIHR203308).}, } @article {pmid38813382, year = {2024}, author = {Patterson, BK and Yogendra, R and Guevara-Coto, J and Mora-Rodriguez, RA and Osgood, E and Bream, J and Parikh, P and Kreimer, M and Jeffers, D and Rutland, C and Kaplan, G and Zgoda, M}, title = {Corrigendum: Case Series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequalae of COVID (PASC).}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1375607}, doi = {10.3389/fmed.2024.1375607}, pmid = {38813382}, issn = {2296-858X}, abstract = {[This corrects the article DOI: 10.3389/fmed.2023.1122529.].}, } @article {pmid38813071, year = {2024}, author = {S, NM and G, R and Sampath, A and Gadwala, R and V, CG and Pakhare, AP and Joshi, R and Singhai, A and Mishra, VN and Khadanga, S}, title = {The Post-COVID-19 Haul on Pulmonary Function: A Prospective Cross-Sectional Study.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e61101}, pmid = {38813071}, issn = {2168-8184}, abstract = {BACKGROUND: Long COVID syndrome, characterized by symptoms like dyspnea, fatigue, and cough, persisting for weeks to months after the initial SARS-CoV-2 infection, poses significant challenges globally. Studies suggest a potential higher risk among females aged 40-50, with symptoms affecting individuals regardless of initial COVID-19 severity, underscoring the need for comprehensive understanding and management.

METHODS: A prospective longitudinal study was conducted at a teaching tertiary care institute in Central India, involving COVID-19 patients from May 2020 to September 2021. Participants, aged 18 or older, diagnosed with COVID-19 and surviving until the last follow-up, were monitored telephonically and during outpatient visits for treatment details and outcomes. Data analysis was done using R software 4.2.1.

RESULTS: The baseline characteristics of the study participants showed a majority of moderate COVID-19 severity (47.5%), with a higher proportion of males (64.8%) affected. Common comorbidities included diabetes (27.1%) and hypertension (22.9%). Long COVID-19 symptoms, notably breathlessness, were prevalent, with females exhibiting a significantly higher association. Pulmonary function abnormalities were associated with both long COVID-19 symptoms and higher COVID-19 severity categories, indicating lasting respiratory impact post-infection.

CONCLUSION: Long after the pandemic, COVID-19 continues to raise concerns due to persistent sequelae, with a majority experiencing long COVID symptoms, particularly those with severe initial illness, including breathlessness and abnormal lung function, highlighting prevalent restrictive lung pattern changes.}, } @article {pmid38812399, year = {2024}, author = {Gangemi, A and Suriano, R and Fabio, RA}, title = {Longitudinal Exploration of Cortical Brain Activity in Cognitive Fog: An EEG Study in Patients with and without Anosmia.}, journal = {Journal of integrative neuroscience}, volume = {23}, number = {5}, pages = {105}, doi = {10.31083/j.jin2305105}, pmid = {38812399}, issn = {0219-6352}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/complications/physiopathology ; Aged ; *Electroencephalography ; *Anosmia/physiopathology/etiology ; Longitudinal Studies ; *Cerebral Cortex/physiopathology ; *Cognitive Dysfunction/physiopathology/etiology ; Event-Related Potentials, P300/physiology ; Beta Rhythm/physiology ; }, abstract = {BACKGROUND: Long-Covid, characterized by persistent symptoms following acute Covid-19 infection, represents a complex challenge for the scientific community. Among the most common and debilitating manifestations, cognitive fog is a neurological disorder characterized by mental confusion and cognitive difficulties. In this study, we investigated the long-term effects of previous Covid-19 infection on cortical brain activity in patients experiencing cognitive fog symptoms in the medium and long term.

METHODS: A total of 40 subjects (20 females and 20 males) aged between 45 and 70 years (mean age (M) = 59.78, standard deviation (SD) = 12.93) participated in this study. This sample included individuals with symptoms of cognitive fog, both with and without anosmia, and a control group comprised of healthy subjects. All electroencephalography (EEG) data were collected in two sessions, 1 month and 8 months after recovery from Covid-19, to measure the neurophysiological parameters of P300 and beta band rhythms.

RESULTS: The results revealed significant differences in the neurophysiological parameters of P300 and beta band rhythms in subjects affected by cognitive fog, and these alterations persist even 8 months after recovery from Covid-19. Interestingly, no significant differences were observed between the participants with anosmia and without anosmia associated with cognitive fog.

CONCLUSIONS: These findings provide a significant contribution to understanding the long-term effects of Covid-19 on the brain and have important implications for future interventions aimed at managing and treating brain fog symptoms. The longitudinal assessment of cortical brain activity helps highlight the persistent impact of the virus on the neurological health of Long-Covid patients.}, } @article {pmid38810786, year = {2024}, author = {Tambling, RR and Hynes, KC and Carolan, K and Charles, D and Moynihan, L}, title = {The Long-COVID Well-Being Scale (LCOVID-WBS): Development of a nascent measure of long-COVID symptoms and impacts.}, journal = {Journal of affective disorders}, volume = {361}, number = {}, pages = {67-73}, doi = {10.1016/j.jad.2024.05.134}, pmid = {38810786}, issn = {1573-2517}, mesh = {Humans ; *COVID-19/psychology ; *Psychometrics ; Male ; Female ; Middle Aged ; Adult ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mental Health ; Surveys and Questionnaires ; Aged ; Factor Analysis, Statistical ; Quality of Life/psychology ; Reproducibility of Results ; }, abstract = {As is now well-known, COVID-19 is a highly contagious disease, which for some can cause symptoms that last long after initial infection. In 2021, a clinical set of symptoms referred to as long-COVID was identified. For many patients, long-COVID is a confusing and frightening multisystem disease, with the potential for myriad negative psychosocial effects, including significant impacts on employment and mental health, and requiring ongoing care. Research and treatment of long-COVID will be facilitated by a sound measure that addresses aspects of well-being, symptom experiences, and psychosocial impacts among long-COVID patients. The present work addresses this need by presenting the results of the development and preliminary psychometrics for the Long-COVID Well-Being Scale (LCOVID-WBS). In an exploratory factor analysis with a panel of 236 participants, researchers identified four factors: Emotional Strain, Physical Ability Strain, Control of Life, and Overall Evaluation of Health. The nascent measure represents the first step to measuring the impacts of long-COVID.}, } @article {pmid38810537, year = {2024}, author = {Tsai, RY and Gau, SY and Ho, YJ and Lin, SY and Ku, CY and Wang, SI and Wei, JC}, title = {Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.}, journal = {Psychiatry research}, volume = {337}, number = {}, pages = {115970}, doi = {10.1016/j.psychres.2024.115970}, pmid = {38810537}, issn = {1872-7123}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology/psychology ; Male ; Retrospective Studies ; *Substance-Related Disorders/epidemiology ; Middle Aged ; Adult ; *Taste Disorders/etiology/epidemiology ; *Olfaction Disorders/etiology/epidemiology/physiopathology ; Aged ; Anosmia/etiology/physiopathology/epidemiology ; Post-Acute COVID-19 Syndrome ; United States/epidemiology ; Young Adult ; }, abstract = {Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.}, } @article {pmid38808863, year = {2024}, author = {Ganesh, R and Yadav, S and Hurt, RT and Mueller, MR and Aakre, CA and Gilman, EA and Grach, SL and Overgaard, J and Snyder, MR and Collins, NM and Croghan, IT and Badley, AD and Razonable, RR and Salonen, BR}, title = {Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241254751}, pmid = {38808863}, issn = {2150-1327}, support = {R01 AI110173/AI/NIAID NIH HHS/United States ; R01 AI120698/AI/NIAID NIH HHS/United States ; R56 AI120698/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Female ; Middle Aged ; Male ; *Cytokines/blood ; *COVID-19/immunology/blood ; Adult ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Interleukin-1beta/blood ; Tumor Necrosis Factor-alpha/blood ; Interleukin-6/blood ; }, abstract = {BACKGROUND: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs.

METHODS: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants.

RESULTS: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α (P < .001) and interleukin 1β (P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs.

DISCUSSION: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.}, } @article {pmid38808823, year = {2024}, author = {Prata, TA and Leite, AS and Augusto, VM and Bretas, DC and Andrade, BH and Oliveira, JDGF and Batista, AP and Machado-Coelho, GLL and Mancuzo, E and Marinho, CC}, title = {Lung function and quality of life one year after severe COVID-19 in Brazil.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {50}, number = {2}, pages = {e20230261}, pmid = {38808823}, issn = {1806-3756}, mesh = {Humans ; *COVID-19/psychology/physiopathology ; *Quality of Life ; Male ; Middle Aged ; Female ; Cross-Sectional Studies ; Brazil/epidemiology ; Aged ; *Respiratory Function Tests ; *Dyspnea/physiopathology/psychology ; SARS-CoV-2 ; Severity of Illness Index ; Lung/physiopathology ; Surveys and Questionnaires ; Walk Test ; Time Factors ; Hospitalization/statistics & numerical data ; }, abstract = {OBJECTIVE: To evaluate symptoms, lung function, and quality of life of a cohort of patients hospitalized for severe COVID-19 12 months after hospital admission.

METHODS: This was a cross-sectional study. We included severe COVID-19 survivors hospitalized in one of three tertiary referral hospitals for COVID-19 in the city of Belo Horizonte, Brazil. Participants were submitted to lung function and six-minute walk tests and completed the EQ-5D-3L questionnaire.

RESULTS: The whole sample comprised 189 COVID-19 survivors (mean age = 59.6 ± 13.4 years) who had been admitted to a ward only (n = 96; 50.8%) or to an ICU (n = 93; 49.2%). At 12 months of follow-up, 43% of patients presented with dyspnea, 27% of whom had a restrictive ventilatory disorder and 18% of whom presented with impaired DLCO. There were no significant differences in FVC, FEV1, and TLC between the survivors with or without dyspnea. However, those who still had dyspnea had significantly more impaired DLCO (14.9% vs. 22.4%; p < 0.020) and poorer quality of life.

CONCLUSIONS: After one year, survivors of severe COVID-19 in a middle-income country still present with high symptom burden, restrictive ventilatory changes, and loss of quality of life. Ongoing follow-up is needed to characterize long COVID-19 and identify strategies to mitigate its consequences.}, } @article {pmid38808198, year = {2024}, author = {Tabarsi, P and Hemmatian, M and Moradi, M}, title = {Long COVID-19 leading to Good's syndrome diagnosis: A clinical case-report and literature review.}, journal = {Clinical case reports}, volume = {12}, number = {6}, pages = {e8962}, pmid = {38808198}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: Good's syndrome (GS) in conjunction with a severe COVID-19 infection, shedding light on the complexities of managing this rare condition that combines thymoma and immunodeficiency.

ABSTRACT: This study delves into the clinical presentation and management of a 63-year-old male diagnosed with Good's syndrome (GS) amid a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. GS, an uncommon association between thymoma and immunodeficiency, remains a clinical mystery, necessitating increased awareness and understanding. Our patient's intricate clinical course, marked by recurrent COVID-19 symptoms and multiple hospitalizations, exemplifies the challenges posed by GS. Through a systematic review of GS cases globally, we highlight its worldwide distribution, with a substantial proportion reported in Europe. Notably, the diagnosis of thymoma often precedes immunodeficiency, emphasizing the importance of vigilance in clinical assessments.}, } @article {pmid38808005, year = {2024}, author = {Dhiman, NR and Joshi, D and Singh, R and Gyanpuri, V and Kumar, A}, title = {Post-COVID-19 headache- NDPH phenotype: a systematic review of case reports.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {5}, number = {}, pages = {1376506}, pmid = {38808005}, issn = {2673-561X}, abstract = {BACKGROUND AND OBJECTIVES: Post-acute COVID-19 syndrome or "long COVID" affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection.

METHODS: Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis.

RESULTS: Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review.

CONCLUSION: NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted.

The review is registered in Prospero with no. Identifier (CRD42022354912).

https://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).}, } @article {pmid38807958, year = {2024}, author = {Antonelli, M and Donelli, D}, title = {Evaluating qigong as integrative support for COVID-19 and Long-COVID-19 rehabilitation: a systematic review.}, journal = {Frontiers in psychology}, volume = {15}, number = {}, pages = {1403130}, pmid = {38807958}, issn = {1664-1078}, abstract = {INTRODUCTION: Amidst the ongoing global impact of COVID-19 on public health, there is an increasing focus on holistic strategies encompassing integrative therapies and rehabilitation techniques, particularly in addressing the challenges posed by Long-COVID-19. This review investigates the potential of Qigong, an ancient Chinese practice characterized by gentle movements, controlled breathing, and meditative elements, within the context of COVID-19.

METHODS: A systematic search of PubMed, EMBASE, Web of Science, Scopus, and Google Scholar was conducted to identify pertinent clinical studies.

RESULTS: Following thorough database scrutiny, nine studies were identified as meeting the eligibility criteria. Across the spectrum of COVID-19 severity, individuals engaging in qigong practice exhibited notable enhancements in both physical and psychological wellbeing, evidenced by ameliorated respiratory symptoms, reduced anxiety levels, enhanced sleep quality, bolstered mental wellbeing, and augmented health-related quality of life. Moreover, qigong training, whether employed independently or in conjunction with other therapies, demonstrated beneficial effects on Long-COVID-19 symptoms, encompassing persistent respiratory issues, dizziness, sleep disturbances, and compromised health-related quality of life.

DISCUSSION: This review underscores the necessity for further investigation to quantify and standardize the contribution of Qigong to COVID-19 recovery and rehabilitation. Such endeavors aim to integrate this accessible and low-impact practice into public health strategies and comprehensive treatment regimens.

The review protocol was registered in the Open Science Framework under the following doi: 10.17605/OSF.IO/7K5X6 (URL: https://osf.io/7k5x6).}, } @article {pmid38806743, year = {2024}, author = {Tsai, J and Grace, A and Espinoza, R and Kurian, A}, title = {Correction: Incidence of long COVID and associated psychosocial characteristics in a large U.S. city.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {59}, number = {10}, pages = {1893}, doi = {10.1007/s00127-024-02687-1}, pmid = {38806743}, issn = {1433-9285}, } @article {pmid38806678, year = {2024}, author = {Buchholz, S and Di Meco, E and Bałkowiec-Iskra, EZ and Sepodes, B and Cavaleri, M}, title = {Generating clinical evidence for treatment and prevention options for long COVID.}, journal = {Nature medicine}, volume = {30}, number = {8}, pages = {2109-2110}, pmid = {38806678}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; }, } @article {pmid38806438, year = {2024}, author = {Li, Y and Lin, J and Gao, J and Tang, L and Liu, Y and Zhang, Z}, title = {Efficacy and safety of hyperbaric oxygen therapy for long COVID: a protocol for systematic review and meta-analysis.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e083868}, pmid = {38806438}, issn = {2044-6055}, mesh = {*Hyperbaric Oxygenation/methods ; Humans ; *Systematic Reviews as Topic ; *Meta-Analysis as Topic ; *COVID-19/therapy ; SARS-CoV-2 ; Research Design ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; }, abstract = {INTRODUCTION: There is still a lack of therapeutic options for long COVID. Several studies have shown the benefit of hyperbaric oxygen therapy (HBOT) on long COVID. However, the efficacy and safety of HBOT for long COVID remain unclear. Therefore, we will conduct this systematic review to assess the feasibility of HBOT as a primary or complemental therapy for long COVID.

METHODS AND ANALYSIS: Databases such as Web of Science, PubMed, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry Platform, Wanfang Database, China National Knowledge Infrastructure, SINOMED, VIP Database and the Chinese Clinical Trial Registry will be searched systematically from the establishment to 9 December 2023. All articles will be reviewed by two independent reviewers. Cochrane risk of bias tool will be used to assess the risk of bias in the study. We will evaluate heterogeneity using a visual inspection of the funnel plot. If an available number of studies are identified, we will perform a meta-analysis.

ETHICS AND DISSEMINATION: No ethical approval is required since this study is based on published articles. The findings will be published in a peer-reviewed journal or disseminated through conference presentations.

PROSPERO REGISTRATION NUMBER: CRD42023482523.}, } @article {pmid38806207, year = {2024}, author = {Smyth, N and Ridge, D and Kingstone, T and Gopal, DP and Alwan, NA and Wright, A and Chaudhry, A and Clark, S and Band, R and Chew-Graham, CA}, title = {People from ethnic minorities seeking help for long COVID: a qualitative study.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {74}, number = {749}, pages = {e814-e822}, pmid = {38806207}, issn = {1478-5242}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/epidemiology/ethnology ; *Ethnic and Racial Minorities ; Health Services Accessibility ; Interviews as Topic ; Patient Acceptance of Health Care/ethnology/psychology ; Post-Acute COVID-19 Syndrome ; Primary Health Care ; *Qualitative Research ; Social Stigma ; United Kingdom ; }, abstract = {BACKGROUND: People from ethnic minority groups are disproportionately affected by COVID-19, less likely to access primary health care, and have reported dissatisfaction with health care. Although the prevalence of long COVID in ethnic minority groups is unclear, such populations are underrepresented in long-COVID specialist clinics and long-COVID lived-experience research, which informed the original long-COVID healthcare guidelines.

AIM: To understand the lived experiences of long COVID in people from ethnic minority groups.

DESIGN AND SETTING: Qualitative study of people living with long COVID in the UK.

METHOD: Semi-structured interviews with people who self-disclosed long COVID were conducted between June 2022 and June 2023 via telephone or video call. Thematic analysis of the data was conducted. People who were living with long COVID, or caring for someone with long COVID, advised on all stages of the research.

RESULTS: Interviews were conducted with 31 participants representing diverse socioeconomic demographics. Help-seeking barriers included little awareness of long COVID or available support, and not feeling worthy of receiving care. Negative healthcare encounters were reported in primary health care; however, these services were crucial for accessing secondary or specialist care. There were further access difficulties and dissatisfaction with specialist care. Experiences of stigma and discrimination contributed to delays in seeking care and unsatisfactory experiences, resulting in feelings of mistrust in health care.

CONCLUSION: Empathy, validation of experiences, and fairness in recognition and support of healthcare needs are required to restore trust in health care and improve the experiences of people with long COVID.}, } @article {pmid38805803, year = {2024}, author = {Rzymski, P and Niedziela, J and Poniedziałek, B and Rosińska, J and Zarębska-Michaluk, D and Sobala-Szczygieł, B and Flisiak, R and Gąsior, M and Jaroszewicz, J}, title = {Humoral anti-SARS-CoV-2 response in patients with different long COVID phenotypes.}, journal = {Virology}, volume = {596}, number = {}, pages = {110118}, doi = {10.1016/j.virol.2024.110118}, pmid = {38805803}, issn = {1096-0341}, mesh = {Humans ; *COVID-19/immunology/virology ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Female ; Male ; Middle Aged ; *Immunoglobulin G/blood ; Aged ; *Immunity, Humoral ; Phenotype ; Post-Acute COVID-19 Syndrome ; Adult ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus/immunology ; Phosphoproteins/immunology ; }, abstract = {Long COVID (LC) is characterized by persistent symptoms following SARS-CoV-2 infection, with various mechanisms offered to explain its pathogenesis. This study explored whether adaptive humoral anti-SARS-CoV-2 responses differ in LC. Unvaccinated COVID-19 convalescents (n = 200) were enrolled, with 21.5% (n = 43) presenting LC three months post-infection. LC diagnosis was based on persistent symptom(s) and alterations in biochemical/clinical markers; three phenotypes were distinguished: cardiological, pulmonary, and psychiatric LC. All three phenotypes were characterized by significantly decreased seroprevalence of IgG antibodies against nucleocapsid (anti-NP). LC was associated with decreased odds of testing positive for anti-NP (OR = 0.35, 95%CI: 0.16-0.78, p = 0.001). Seropositive LC patients had lower anti-S1 and anti-S2 levels than individuals without LC, and those with pulmonary and psychological phenotypes also revealed decreased anti-RBD concentrations. The results indicate that LC can be characterized by diminished humoral response to SARS-CoV-2. The potential implication of this phenomenon in post-acute viral sequelae is discussed.}, } @article {pmid38805375, year = {2024}, author = {Schröder, D and Schmachtenberg, T and Heinemann, S and Müllenmeister, C and Roder, S and El-Sayed, I and Heesen, G and Königs, G and Dopfer-Jablonka, A and Hummers, E and Mikuteit, M and Dopfer, C and Grewendorf, S and Niewolik, J and Steffens, S and Doze, V and Klawonn, F and Müller, F}, title = {Parenting and Gender as Impact Factors for Social Participation, Quality of Life, and Mental Health in Long COVID.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241255592}, pmid = {38805375}, issn = {2150-1327}, mesh = {Humans ; *Quality of Life ; Male ; Female ; *COVID-19/psychology/epidemiology ; Middle Aged ; *Mental Health ; Cross-Sectional Studies ; Sex Factors ; Adult ; *Parenting/psychology ; *Social Participation ; Aged ; SARS-CoV-2 ; Qualitative Research ; Adaptation, Psychological ; Anxiety/psychology/epidemiology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: This study aims to investigate the impact of gender and parental tasks on social participation, health-related quality of life (hrQoL), and mental health in persons with long COVID.

METHODS: A mixed-methods approach was followed including a cross-sectional web-based survey and semi-structured interviews. Multivariable linear regressions were used to quantify the effect of gender and parenting tasks on social participation, hrQoL, and mental health. Qualitative data from interviews with participants experiencing long COVID symptoms was analyzed using content analysis.

RESULTS: Data from 920 participants in the quantitative study and 25 participants in the qualitative study was analyzed. Parenting tasks were associated with increased impairments in family and domestic responsibilities in persons with long COVID compared to lower impairments in persons without long COVID (P = .02). The qualitative data indicate that coping with long COVID and pursuing parenting tasks limit participants' ability to perform leisure activities and attend social gatherings. In long COVID, men had higher anxiety symptoms than women, and in those without long COVID, the opposite was observed (P < .001). In the qualitative study, participants expressed feelings of dejection and pessimism about their future private, occupational, and health situations. No differences between the genders could be observed.

CONCLUSIONS: Long COVID is associated with impairments in family and domestic responsibilities in individuals who have parenting tasks. Among participants with long COVID, anxiety symptoms are higher in men than women.}, } @article {pmid38804402, year = {2024}, author = {Stepanova, N and Korol, L and Ostapenko, T and Marchenko, V and Belousova, O and Snisar, L and Shifris, I and Kolesnyk, M}, title = {Pre-Infection Nutritional Status, Oxidative Stress, and One-Year-Long COVID Persistence in Patients Undergoing Hemodialysis: A Prospective Cohort Study.}, journal = {Clinics and practice}, volume = {14}, number = {3}, pages = {892-905}, pmid = {38804402}, issn = {2039-7275}, abstract = {BACKGROUND: Nutritional status's role in long COVID is evident in the general population, yet unexplored in patients undergoing hemodialysis (HD), posing a research gap. We hypothesized that pre-infection undernutrition in HD patients might impact long COVID persistence by accelerating oxidative stress. The present study aimed to investigate the association between pre-infection nutritional status, oxidative stress, and one-year-long COVID persistence in HD patients.

METHODS: This prospective observational cohort study enrolled 115 HD patients with confirmed COVID-19. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score twice: before infection and three months post-infection. Oxidative markers included malondialdehyde (MDAs), ceruloplasmin, transferrin, and sulfhydryl groups. The endpoint was one-year-long COVID persistence.

RESULTS: Moderate pre-infection CONUT scores were associated with heightened severe undernutrition risk (p < 0.0001), elevated MDAs (p < 0.0001), and reduced ceruloplasmin levels (p = 0.0009) at three months post-COVID-19 compared to light CONUT scores. Pre-infection CONUT score independently predicted post-COVID oxidative damage [OR 2.3 (95% CI 1.2; 4.6), p < 0.0001] and one-year-long COVID persistence [HR 4.6 (95% CI 1.4; 9.9), p < 0.0001], even after adjusting for potential confounders.

CONCLUSION: Moderate pre-infection undernutrition heightens post-COVID oxidative stress and increases the risk of one-year-long COVID persistence in HD patients.}, } @article {pmid38804045, year = {2024}, author = {Tang, Y and Xu, M and Luo, B and Wang, Y and Chen, Y and Yu, G and Yang, G and Gao, S and Wang, P}, title = {Highly sensitive detection of a long-COVID-related SNP in LZTFL1 allele with Pyrococcus furiosus Argonaute in point-of-care settings.}, journal = {Acta biochimica et biophysica Sinica}, volume = {56}, number = {7}, pages = {1089-1092}, pmid = {38804045}, issn = {1745-7270}, mesh = {*Polymorphism, Single Nucleotide ; Humans ; *COVID-19/virology/genetics ; *Pyrococcus furiosus/genetics ; *Alleles ; SARS-CoV-2/genetics/isolation & purification ; Argonaute Proteins/genetics/metabolism ; Point-of-Care Systems ; }, } @article {pmid38802702, year = {2024}, author = {Dehhaghi, M and Heydari, M and Panahi, HKS and Lewin, SR and Heng, B and Brew, BJ and Guillemin, GJ}, title = {The roles of the kynurenine pathway in COVID-19 neuropathogenesis.}, journal = {Infection}, volume = {52}, number = {5}, pages = {2043-2059}, pmid = {38802702}, issn = {1439-0973}, support = {Macquarie University Research Excellence Scholarship//Macquarie University/ ; APP1176660//National Health and Medical Research Council/ ; }, mesh = {*Kynurenine/metabolism ; Humans ; *COVID-19/metabolism ; *SARS-CoV-2 ; Cytokines/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Cytokine Release Syndrome ; Post-Acute COVID-19 Syndrome ; Tryptophan/metabolism ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.}, } @article {pmid38802280, year = {2024}, author = {Lawson, CA and Moss, AJ and Arnold, JR and Bagot, C and Banerjee, A and Berry, C and Greenwood, J and Hughes, AD and Khunti, K and Mills, NL and Neubauer, S and Raman, B and Sattar, N and Leavy, OC and Richardson, M and Elneima, O and McAuley, HJ and Shikotra, A and Singapuri, A and Sereno, M and Saunders, R and Harris, V and Houchen-Wolloff, L and Greening, NJ and Harrison, E and Docherty, AB and Lone, NI and Quint, JK and Chalmers, J and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Evans, R and Wain, LV and Brightling, C and McCann, GP and , }, title = {Long COVID and cardiovascular disease: a prospective cohort study.}, journal = {Open heart}, volume = {11}, number = {1}, pages = {}, pmid = {38802280}, issn = {2053-3624}, mesh = {Humans ; *COVID-19/epidemiology/complications/diagnosis ; Male ; Female ; *Cardiovascular Diseases/epidemiology/diagnosis ; Prospective Studies ; Middle Aged ; Aged ; Risk Factors ; Hospitalization/statistics & numerical data ; Time Factors ; SARS-CoV-2 ; Recovery of Function ; }, abstract = {BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.

OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.

METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.

RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).

CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.

TRAIL REGISTRATION NUMBER: ISRCTN10980107.}, } @article {pmid38802273, year = {2024}, author = {Adam, R and Lotankar, Y and Sas, C and Powell, D and Martinez, V and Green, S and Cooper, J and Bradbury, K and Sive, J and Hill, DL}, title = {Understanding patterns of fatigue in health and disease: protocol for an ecological momentary assessment study using digital technologies.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e081416}, pmid = {38802273}, issn = {2044-6055}, mesh = {Humans ; *Fatigue/etiology ; *COVID-19 ; *Ecological Momentary Assessment ; Heart Failure/physiopathology ; Digital Technology ; Multiple Myeloma/complications ; SARS-CoV-2 ; Self Report ; Research Design ; Wearable Electronic Devices ; }, abstract = {INTRODUCTION: Fatigue is prevalent across a wide range of medical conditions and can be debilitating and distressing. It is likely that fatigue is experienced differently according to the underlying aetiology, but this is poorly understood. Digital health technologies present a promising approach to give new insights into fatigue.The aim of this study is to use digital health technologies, real-time self-reports and qualitative interview data to investigate how fatigue is experienced over time in participants with myeloma, long COVID, heart failure and in controls without problematic fatigue. Objectives are to understand which sensed parameters add value to the characterisation of fatigue and to determine whether study processes are feasible, acceptable and scalable.

METHODS AND ANALYSIS: An ecological momentary assessment study will be carried out over 2 or 4 weeks (participant defined). Individuals with fatigue relating to myeloma (n=10), heart failure (n=10), long COVID (n=10) and controls without problematic fatigue or a study condition (n=10) will be recruited. ECG patches will measure heart rate variability, respiratory rate, body temperature, activity and posture. A wearable bracelet accompanied by environment beacons will measure physical activity, sleep and room location within the home. Self-reports of mental and physical fatigue will be collected via smartphone app four times daily and on-demand. Validated fatigue and affect questionnaires will be completed at baseline and at 2 weeks. End-of-study interviews will investigate experiences of fatigue and study participation. A feedback session will be offered to participants to discuss their data.Data will be analysed using multilevel modelling and machine learning. Interviews and feedback sessions will be analysed using content or thematic analyses.

ETHICS AND DISSEMINATION: This study was approved by the East of England-Cambridge East Research Ethics Committee (22/EE/0261). The results will be disseminated in peer-reviewed journals and at international conferences.

TRIAL REGISTRATION NUMBER: NCT05622669.}, } @article {pmid38800959, year = {2024}, author = {Calvache-Mateo, A and Reychler, G and Heredia-Ciuró, A and Martín-Núñez, J and Ortiz-Rubio, A and Navas-Otero, A and Valenza, MC}, title = {Respiratory training effects in Long COVID-19 patients: a systematic review and meta-analysis.}, journal = {Expert review of respiratory medicine}, volume = {18}, number = {3-4}, pages = {207-217}, doi = {10.1080/17476348.2024.2358933}, pmid = {38800959}, issn = {1747-6356}, mesh = {Humans ; *COVID-19 ; *Breathing Exercises ; *Muscle Strength ; *Respiratory Muscles/physiopathology ; Dyspnea/physiopathology ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: To date, it is unknown whether respiratory training interventions can benefit Long COVID-19 patients. The main objective was to analyze the effects of respiratory training on patients with Long COVID-19, concretely on respiratory muscle strength, lung function, dyspnea, and functional capacity.

METHODS: We performed a systematic review following PRISMA statement using PubMed, Scopus, and PEDro (last search November 2023). The risk of bias was assessed using the Cochrane tool. We included randomized controlled trials testing the effect of respiratory training interventions in Long COVID-19 patients versus no intervention, control, or placebo intervention. The data was pooled, and a meta-analysis was complete.

RESULTS: We selected 7 studies, which included 572 patients. Meta-analysis results show significant differences in favor of respiratory training in respiratory muscle strength (MD = 13.71; 95% CI = 5.41; 22; p = 0.001), dyspnea (SDM = 1.39; 95% CI = 0.33; 2.46; p = 0.01) and functional capacity (SDM = 0.90; 95% CI = 0.37; 1.43; p = 0.0009), but not in lung function (MD = 0.28; 95%CI = -0.27; 0.83; p = 0.32).

CONCLUSION: The results of this systematic review with meta-analysis suggest that respiratory training improves respiratory muscle strength and functional capacity in Long COVID-19 patients, as well as dyspnea if combined with therapeutic exercise. However, respiratory training does not improve lung function in these patients.

CRD42022371820.}, } @article {pmid38800803, year = {2024}, author = {Henderson, AD and Butler-Cole, BF and Tazare, J and Tomlinson, LA and Marks, M and Jit, M and Briggs, A and Lin, LY and Carlile, O and Bates, C and Parry, J and Bacon, SC and Dillingham, I and Dennison, WA and Costello, RE and Wei, Y and Walker, AJ and Hulme, W and Goldacre, B and Mehrkar, A and MacKenna, B and , and Herrett, E and Eggo, RM}, title = {Clinical coding of long COVID in primary care 2020-2023 in a cohort of 19 million adults: an OpenSAFELY analysis.}, journal = {EClinicalMedicine}, volume = {72}, number = {}, pages = {102638}, pmid = {38800803}, issn = {2589-5370}, abstract = {BACKGROUND: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England.

METHODS: With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models.

FINDINGS: We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5-179) and 100.5 in men (99.5-102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record.

INTERPRETATION: In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID.

FUNDING: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).}, } @article {pmid38800038, year = {2024}, author = {Sadowski, J and Klaudel, T and Rombel-Bryzek, A and Bułdak, RJ}, title = {Cognitive dysfunctions in the course of SARS‑CoV‑2 virus infection, including NeuroCOVID, frontal syndrome and cytokine storm (Review).}, journal = {Biomedical reports}, volume = {21}, number = {1}, pages = {103}, pmid = {38800038}, issn = {2049-9442}, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of patients. The present study discussed the impact of immunological processes on structural and functional changes in the central nervous system and the related cognitive disorders. The purpose of the present review was to analyse and discuss available information from the scientific literature considering the possible relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and cognitive impairment, including NeuroCOVID, frontal syndrome and cytokine storm. A systematic literature review was conducted using: Google Scholar, Elsevier and the PubMed database. When searching for materials, the following keywords were used: 'cognitive dysfunctions', 'SARS-CoV-2', 'COVID-19', 'Neuro-SARS2', 'NeuroCOVID', 'frontal syndrome', 'cytokine storm', 'Long COVID-19'. A total of 96 articles were included in the study. The analysis focused on the characteristics of each study's materials, methods, results and conclusions. SARS-CoV-2 infection may induce or influence existing cognitive disorders of various nature and severity. The influence of immunological factors related to the response against SARS-CoV-2 on the disturbance of cerebral perfusion, the functioning of nerve cells and the neuroprotective effect has been demonstrated. Particular importance is attached to the cytokine storm and the related difference between pro- and anti-inflammatory effects, oxidative stress, disturbances in the regulation of the hypothalamic-pituitary-adrenal axis and the stress response of the body.}, } @article {pmid38798861, year = {2024}, author = {Sinaga, BY and Siagian, P and Sinaga, JP and Samodra, YL}, title = {Fatigue in healthcare workers with mild COVID-19 survivors in Indonesia.}, journal = {Narra J}, volume = {4}, number = {1}, pages = {e656}, pmid = {38798861}, issn = {2807-2618}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology ; Adult ; *Fatigue/epidemiology/etiology ; Cross-Sectional Studies ; Indonesia/epidemiology ; *Health Personnel ; Risk Factors ; Middle Aged ; Young Adult ; Post-Acute COVID-19 Syndrome ; Survivors/statistics & numerical data ; SARS-CoV-2 ; }, abstract = {Persistent symptoms after the coronavirus disease 2019 (COVID-19, known as post-COVID syndrome (PCS), presented an ongoing health burden among COVID-19 survivors, including health workers. The existence of fatigue in mild COVID-19 survivors has not been widely reported. The aim of this study was to present the symptoms of fatigue in healthcare workers who experienced mild COVID-19 and the factors associated with fatigue. A cross-sectional study was conducted at H. Adam Malik General Hospital in Medan, Indonesia, from September to December 2022, included doctors, nurses, ancillary workers, and medical support workers who experienced mild COVID-19. Fatigue was measured by a fatigue assessment scale (FAS). The assessed possible risk factors were gender, age, vaccination history, comorbid, presence of PCS, duration of PCS symptoms, and number of PCS symptoms. The Chi-squared or Fisher's exact tests were used to assess the association between the incidence of fatigue and risk factors. A total of 100 healthcare workers of mild COVID-19 survivors were included. Most of them were nurses (58%), women (81%), and aged 19-30 years old (36%). The majority had incomplete vaccination history (64%), experienced PCS (71%), no comorbidities (61%), and experienced <3 months of PCS symptoms (55%). Mild to moderate fatigue was found in 23% of healthcare workers and only 1% experienced severe fatigue. No significant association was found between gender, vaccination history, and comorbidities with the incidence of fatigue. However, a significant association was observed between age (p=0.021), the presence of PCS (p=0.041), and the number of PCS symptoms (p=0.047) with fatigue incidence. Furthermore, there were significant associations between symptoms of PCS (confusion (p=0.004), insomnia (p=0.001), myalgia (p=0.035), arthralgia (p=0.028), throat pain (p=0.042), headache (p=0.042), and chest pain (p=0.011)) with fatigue. These findings can contribute to providing the necessary support for mild COVID-19 survivors and persistent fatigue.}, } @article {pmid38798608, year = {2024}, author = {Schuermans, A and Verstraete, A and Lammi, V and Nakanishi, T and Ardissino, M and Van den Eynde, J and Sun, B and Georgakis, MK and Guillen-Guio, B and Wain, LV and Brightling, CE and , and Van Weyenbergh, J and Lewandowski, AJ and Raman, B and Zeberg, H and Ollila, HM and Burgess, S and Natarajan, P and Honigberg, MC and Freson, K and Vanassche, T and Verhamme, P}, title = {Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.17.24307553}, pmid = {38798608}, abstract = {SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. Here, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (n cases =3,018; n controls =994,582). Primary analyses revealed that each unit increase in the log-odds of genetically predicted venous thromboembolism risk was associated with 1.21-fold odds of long COVID (95%CI: 1.08-1.35; P =1.2 × 10 [-3]). This association was independent of acute COVID-19 severity, robust across genetic instruments and methods, and replicated in external datasets for both venous thromboembolism and long COVID. Downstream analyses using gene-specific instruments, along with protein and gene expression data, suggested the protease-activated receptor 1 (PAR-1) as a potential molecular contributor to long COVID. These findings provide human genetic evidence implicating thromboembolism in long COVID pathogenesis. .}, } @article {pmid38798174, year = {2024}, author = {Muirhead, NL}, title = {Medical students highlight the importance of medical education, kindness, compassion and belief when learning about patients with myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {54}, number = {2}, pages = {118-119}, doi = {10.1177/14782715241255977}, pmid = {38798174}, issn = {2042-8189}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology ; *Empathy ; *Students, Medical/psychology ; Education, Medical ; Physician-Patient Relations ; }, } @article {pmid38797051, year = {2024}, author = {Saito, S and Shahbaz, S and Osman, M and Redmond, D and Bozorgmehr, N and Rosychuk, RJ and Lam, G and Sligl, W and Cohen Tervaert, JW and Elahi, S}, title = {Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome.}, journal = {Journal of autoimmunity}, volume = {147}, number = {}, pages = {103267}, doi = {10.1016/j.jaut.2024.103267}, pmid = {38797051}, issn = {1095-9157}, support = {//CIHR/Canada ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/immunology/blood ; *COVID-19/immunology/blood/complications ; Female ; Male ; Middle Aged ; *SARS-CoV-2/immunology ; Adult ; *Erythropoiesis/immunology ; Galectins/blood/immunology ; Cytokines/blood/metabolism ; Post-Acute COVID-19 Syndrome ; Inflammation/immunology ; Nerve Tissue Proteins/immunology/blood ; }, abstract = {A substantial number of patients recovering from acute SARS-CoV-2 infection present serious lingering symptoms, often referred to as long COVID (LC). However, a subset of these patients exhibits the most debilitating symptoms characterized by ongoing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). We specifically identified and studied ME/CFS patients from two independent LC cohorts, at least 12 months post the onset of acute disease, and compared them to the recovered group (R). ME/CFS patients had relatively increased neutrophils and monocytes but reduced lymphocytes. Selective T cell exhaustion with reduced naïve but increased terminal effector T cells was observed in these patients. LC was associated with elevated levels of plasma pro-inflammatory cytokines, chemokines, Galectin-9 (Gal-9), and artemin (ARTN). A defined threshold of Gal-9 and ARTN concentrations had a strong association with LC. The expansion of immunosuppressive CD71[+] erythroid cells (CECs) was noted. These cells may modulate the immune response and contribute to increased ARTN concentration, which correlated with pain and cognitive impairment. Serology revealed an elevation in a variety of autoantibodies in LC. Intriguingly, we found that the frequency of 2B4[+]CD160[+] and TIM3[+]CD160[+] CD8[+] T cells completely separated LC patients from the R group. Our further analyses using a multiple regression model revealed that the elevated frequency/levels of CD4 terminal effector, ARTN, CEC, Gal-9, CD8 terminal effector, and MCP1 but lower frequency/levels of TGF-β and MAIT cells can distinguish LC from the R group. Our findings provide a new paradigm in the pathogenesis of ME/CFS to identify strategies for its prevention and treatment.}, } @article {pmid38796360, year = {2024}, author = {Angelhoff, C and Duchen, K and Ertzgaard, P and Rytterström, P}, title = {Navigating an unfamiliar world - Parents' experiences of having a child with post COVID-19.}, journal = {Journal of pediatric nursing}, volume = {77}, number = {}, pages = {e565-e572}, doi = {10.1016/j.pedn.2024.05.023}, pmid = {38796360}, issn = {1532-8449}, mesh = {Humans ; *COVID-19/psychology ; *Parents/psychology ; Female ; Male ; *Qualitative Research ; Child ; Adult ; SARS-CoV-2 ; Child, Preschool ; Adaptation, Psychological ; Adolescent ; Parent-Child Relations ; Middle Aged ; }, abstract = {BACKGROUND: Post COVID-19 diagnosis in children has been difficult as there has been a lack of knowledge within the healthcare system, leading to uncertainty concerning how these children should be assessed and treated. To understand the aspects of how parents experience seeking care for their child with an array of symptoms and how the child's symptoms affect their everyday life and family situation, we need to listen to the parents' stories about having a child living with post COVID-19.

PURPOSE: To describe parents' experiences of seeking professional care for their child with post COVID-19 symptoms and what kinds of impacts there are on their children's daily life.

DESIGN AND METHODS: A qualitative study with an inductive and exploratory approach including seventeen parents of children with post COVID-19. Face-to-face interviews were conducted between October 2022 and March 2023 and analyzed with thematic analysis.

RESULTS: The findings describe how the parents' constant struggle for their child and how the child's symptoms affect their daily life and their family situation in three themes: Navigating the unknown, Navigating life with post COVID-19, and Navigating between fear and hope for an uncertain future.

CONCLUSIONS: This study corroborates the parents' struggle for acceptance of the children's problems in the health system.

PRACTICE IMPLICATIONS: It is important that health care focuses on the everyday world and the problems that the child and parents express to understand the family's perspective and the problems that arise in everyday life.}, } @article {pmid38796311, year = {2024}, author = {Reed, S and Pansini, M and Diamond, C and Banerjee, A and Thomaides Brears, H and Chowdhury, O}, title = {Multi-organ abnormalities assessed by a single MRI scan in individuals with blood cancer.}, journal = {European journal of internal medicine}, volume = {128}, number = {}, pages = {150-152}, doi = {10.1016/j.ejim.2024.05.025}, pmid = {38796311}, issn = {1879-0828}, mesh = {Humans ; Male ; Female ; *COVID-19/diagnostic imaging/complications ; Middle Aged ; Prospective Studies ; Aged ; *Hematologic Neoplasms/diagnostic imaging ; Adult ; SARS-CoV-2 ; Magnetic Resonance Imaging ; Case-Control Studies ; Multiple Organ Failure/diagnostic imaging/etiology ; }, abstract = {BACKGROUND: During the COVID-19 pandemic individuals with all blood cancers were classified as clinically vulnerable and at high risk of complications and death. Our study sought to determine if individuals with specific blood cancers were at a heightened risk of longer term organ impairment, secondary to SARS-CoV-2 infection.

METHODS: We set up a prospective observational study, utilising quantitative multi-parametric MRI to determine organ health over time in patients with specific blood cancers who had recovered from COVID-19.

RESULTS: Multi-organ abnormality was more prevalent in blood cancer patients than in healthy controls (42 % vs 6 % p < 0.001) but comparable to the long COVID controls (42 % vs 33 %, p > 0.05). At 6 month follow up scans, organ abnormalities persisted in most individuals with blood cancer (71 % ≥1 organ and 52 % multi-organ).

CONCLUSION: A multi-organ MRI platform offers the capacity to accurately evaluate organ health dynamically in blood cancers and detect asymptomatic organ impairment. The application of multi-organ MRI could aid early detection and longitudinal monitoring of organ impairment, potentially guiding more personalised treatment strategies and improving clinical outcomes in many rare diseases.}, } @article {pmid38795941, year = {2024}, author = {Mauro, M and Cegolon, L and Bestiaco, N and Zulian, E and Larese Filon, F}, title = {Heart Rate Variability Modulation Through Slow-Paced Breathing in Health Care Workers with Long COVID: A Case-Control Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.05.021}, pmid = {38795941}, issn = {1555-7162}, abstract = {BACKGROUND: Long COVID is a syndrome persisting 12+ weeks after COVID-19 infection, impacting life and work ability. Autonomic nervous system imbalance has been hypothesized as the cause. This study aims to investigate cardiovascular autonomic function in health care workers (HCWs) with Long COVID and the effectiveness of slow-paced breathing (SPB) on autonomic modulation.

METHODS: From December 1, 2022 to March 31, 2023, 6655 HCWs of the University Hospitals of Trieste (Northeast Italy) were asked to participate in the study by company-email. Inclusion/exclusion criteria were assessed. Global health status and psychosomatic disorders were evaluated through validated questionnaires. Heart rate variability was assessed by finger-photoplethysmography during spontaneous breathing and SPB, which stimulate vagal response. Long COVID HCWs (G1) were contrasted with Never infected (G2) and Fully recovered COVID-19 workers (G3).

RESULTS: There were 126 HCWs evaluated. The 58 Long COVID were assessed at a median time because COVID-19 of 419.5 days (interquartile range 269-730) and had significantly more psychosomatic symptoms and lower detectability of spontaneous systolic pressure oscillation at 0.1 Hz (Mayer wave - baroreflex arc) during spontaneous breathing compared with 53 never-infected and 14 fully-recovered HCWs (19%, 42%, and 40%, respectively, P = .027). During SPB, the increase in this parameter was close to controls (91.2%, 100%, and 100%, respectively, P = .09). No other differences in heart rate variability parameters were found among groups.

CONCLUSIONS: Resting vascular modulation was reduced in Long COVID, while during SPB, baroreflex sensitivity effectively improved. Long-term studies are needed to evaluate whether multiple sessions of breathing exercises can restore basal vascular reactivity and reduce cardiovascular risk in these patients.}, } @article {pmid38794850, year = {2025}, author = {Bai, X and Cai, X and Zhou, J and Yang, W}, title = {COVID-19 infection, resilience, and depressive symptoms: the protective role of family functioning for aging Chinese adults in Hong Kong.}, journal = {Aging & mental health}, volume = {29}, number = {1}, pages = {59-68}, doi = {10.1080/13607863.2024.2356874}, pmid = {38794850}, issn = {1364-6915}, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Aging/psychology ; *COVID-19/psychology/epidemiology ; *Depression/psychology/epidemiology ; East Asian People ; *Family Relations/psychology ; Hong Kong/epidemiology ; Protective Factors ; *Resilience, Psychological ; Sex Factors ; }, abstract = {OBJECTIVES: Older adults are at an elevated risk of experiencing long COVID, with post-COVID-19 depressive symptoms being prevalent. However, the protective factors against this remain understudied. This study examined (a) the role of resilience in the association between COVID-19 infection and depressive symptoms in aging adults; (b) the moderating role of family functioning in the relationships between COVID-19 and resilience and between resilience and depressive symptoms; and (c) potential gender differences in the moderation.

METHOD: Data were drawn from the first wave of the Panel Study of Active Ageing and Society, a representative survey of Hong Kong adults aged 50 or above. Mediation and moderated mediation analyses were conducted.

RESULTS: Approximately 35% of the participants had tested positive for COVID-19. Resilience significantly mediated the association between COVID-19 infection and post-COVID-19 depressive symptoms (p < 0.001). Family functioning was a significant moderator: the COVID-19-resilience association was stronger, and the resilience-depressive symptoms association was weaker among participants with higher family functioning. The moderating role of family functioning was more salient in women than in men.

CONCLUSION: Resilience can protect aging adults from post-COVID-19 depressive symptoms. Interventions for enhancing family functioning may promote the formation of resilience, especially among older women.}, } @article {pmid38794767, year = {2024}, author = {Tan, Y and Xie, Y and Dong, G and Yin, M and Shang, Z and Zhou, K and Bao, D and Zhou, J}, title = {The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial.}, journal = {Nutrients}, volume = {16}, number = {10}, pages = {}, pmid = {38794767}, issn = {2072-6643}, mesh = {Humans ; *Hydrogen ; *Dyspnea ; *Fatigue ; Male ; Female ; Single-Blind Method ; *COVID-19/complications ; Middle Aged ; Pilot Projects ; Water ; SARS-CoV-2 ; Adult ; Post-Acute COVID-19 Syndrome ; Aged ; }, abstract = {(1) Background: Hydrogen (H2) may be a potential therapeutic agent for managing Long COVID symptoms due to its antioxidant and anti-inflammatory properties. However, more scientific literature is needed to describe the effects of H2 administration on treating symptoms. A study aimed to investigate the impact of hydrogen-rich water (HRW) administration on the fatigue and dyspnea of Long-COVID patients for 14 consecutive days. (2) Methods: In this randomized, single-blind, placebo-controlled study, 55 participants were recruited, and 23 of them were excluded. A total of 32 eligible participants were randomized into a hydrogen-rich water (HRW) group (n = 16) and a placebo water (PW) group (n = 16) in which they were instructed to consume hydrogen-rich water or placebo water for 14 days, respectively. The participants completed the Fatigue Severity Scale (FSS), Six-Minute Walk Test (6MWT), 30 s Chair Stand Test (30s-CST), Modified Medical Research Council Dyspnea Rating Scale (mMRC), Pittsburgh Sleep Quality Index (PSQI), and depression anxiety stress scale (DASS-21) before and after the intervention. A linear mixed-effects model was used to analyze the effects of HRW. Cohen's d values were used to assess the effect size when significance was observed. The mean change with 95% confidence intervals (95% CI) was also reported. (3) Results: The effects of HRW on lowering FSS scores (p = 0.046, [95% CI = -20.607, -0.198, d = 0.696] and improving total distance in the 6WMT (p < 0.001, [95% CI = 41.972, 61.891], d = 1.010), total time for the 30s-CST (p = 0.002, [95% CI = 1.570, 6.314], d = 1.190), and PSQI scores (p = 0.012, [95% CI = -5.169, 0.742], d = 1.274) compared to PW were of a significantly moderate effect size, while there was no significant difference in mMRC score (p = 0.556) or DASS-21 score (p > 0.143). (4) Conclusions: This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients.}, } @article {pmid38793754, year = {2024}, author = {Nguyen, KH and McChesney, C and Patel, R and Bednarczyk, RA and Vasudevan, L and Corlin, L}, title = {Association between COVID-19 Booster Vaccination and COVID-19 Outcomes among U.S. Adults.}, journal = {Vaccines}, volume = {12}, number = {5}, pages = {}, pmid = {38793754}, issn = {2076-393X}, abstract = {Understanding the association between booster vaccination and COVID-19 outcomes can help strengthen post-pandemic messaging and strategies to increase vaccination and reduce severe and long-term consequences of COVID-19. Using the Household Pulse Survey data collected from U.S. adults from 9 December 2022 to 13 February 2023 (n = 214,768), this study assessed the relationship between COVID-19 booster vaccination and COVID-19 outcomes (testing positive for COVID-19, moderate/severe COVID-19, and long COVID). Disparities were found in COVID-19 outcomes (e.g., testing positive for COVID-19, moderate/severe COVID-19, and long COVID) by sociodemographic characteristics, region of residence, food insecurity status, mental health status, disability status, and housing type. Receipt of a COVID-19 booster vaccination was negatively associated with testing positive for COVID-19 (aOR = 0.75, 95%CI: 0.72,0.79), having moderate/severe COVID-19 (aOR = 0.92, 95%CI: 0.88, 0.97), or having long COVID (aOR = 0.86 (0.80, 0.91)). Even among those who tested positive for COVID-19, those who received the booster vaccine were less likely to have moderate/severe COVID-19 and less likely to have long COVID. Communicating the benefits of COVID-19 booster vaccination, integrating vaccination in patient visits, and reducing access barriers can increase vaccination uptake and confidence for all individuals and protect them against the severe negative outcomes of COVID-19.}, } @article {pmid38793710, year = {2024}, author = {Kumar, A and Tripathi, P and Kumar, P and Shekhar, R and Pathak, R}, title = {From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2.}, journal = {Vaccines}, volume = {12}, number = {5}, pages = {}, pmid = {38793710}, issn = {2076-393X}, abstract = {Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.}, } @article {pmid38793097, year = {2024}, author = {Michalas, M and Katsaras, S and Spetsioti, S and Spaggoulakis, D and Antonoglou, A and Asimakos, A and Katsaounou, P and Christakou, A}, title = {The Effect of Physiotherapy on Dyspnea, Muscle Strength and Functional Status in Patients with Long COVID Syndrome.}, journal = {Journal of personalized medicine}, volume = {14}, number = {5}, pages = {}, pmid = {38793097}, issn = {2075-4426}, abstract = {BACKGROUND: Patients who were infected with COVID-19 may experience Long COVID syndrome. We examined the effectiveness of physiotherapy on dyspnea, muscle strength, and functional status in Long COVID syndrome.

METHODS: The exercise group underwent an 8-week supervised physiotherapeutic program consisting of interval aerobic exercise and strengthening exercises, each lasting 30 min. The control group did not engage in any exercise. Dyspnea, muscle strength, and functional status were assessed at the beginning and end of the intervention in both groups.

RESULTS: No significant baseline differences were found between the two groups. The exercise group demonstrated improvements compared to baseline in dyspnea, quadriceps muscle strength, and functional status. Specifically, there was a significant increase of 3.7 lifts in the 60-s sit-to-stand test (p = 0.01), an increase of 5.86 kg in right quadriceps muscle strength (p = 0.03), an increase of 8.26 kg in left quadriceps muscle strength (p = 0.01), and a decrease in dyspnea score by 0.95 points (p = 0.02).

CONCLUSIONS: Similar studies have reported improvements in dyspnea, muscle strength, and functional status in the exercise group. However, further research with larger sample sizes is needed to confirm these findings.}, } @article {pmid38792452, year = {2024}, author = {Han, M and Chang, T and Chun, HR and Jo, S and Jo, Y and Yu, DH and Yoo, S and Cho, SI}, title = {Symptoms and Conditions in Children and Adults up to 90 Days after SARS-CoV-2 Infection: A Retrospective Observational Study Utilizing the Common Data Model.}, journal = {Journal of clinical medicine}, volume = {13}, number = {10}, pages = {}, pmid = {38792452}, issn = {2077-0383}, abstract = {Background/Objectives: There have been widespread reports of persistent symptoms in both children and adults after SARS-CoV-2 infection, giving rise to debates on whether it should be regarded as a separate clinical entity from other postviral syndromes. This study aimed to characterize the clinical presentation of post-acute symptoms and conditions in the Korean pediatric and adult populations. Methods: A retrospective analysis was performed using a national, population-based database, which was encoded using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). We compared individuals diagnosed with SARS-CoV-2 to those diagnosed with influenza, focusing on the risk of developing prespecified symptoms and conditions commonly associated with the post-acute sequelae of COVID-19. Results: Propensity score matching yielded 1,656 adult and 343 pediatric SARS-CoV-2 and influenza pairs. Ninety days after diagnosis, no symptoms were found to have elevated risk in either adults or children when compared with influenza controls. Conversely, at 1 day after diagnosis, adults with SARS-CoV-2 exhibited a significantly higher risk of developing abnormal liver function tests, cardiorespiratory symptoms, constipation, cough, thrombophlebitis/thromboembolism, and pneumonia. In contrast, children diagnosed with SARS-CoV-2 did not show an increased risk for any symptoms during either acute or post-acute phases. Conclusions: In the acute phase after infection, SARS-CoV-2 is associated with an elevated risk of certain symptoms in adults. The risk of developing post-acute COVID-19 sequelae is not significantly different from that of having postviral symptoms in children in both the acute and post-acute phases, and in adults in the post-acute phase. These observations warrant further validation through studies, including the severity of initial illness, vaccination status, and variant types.}, } @article {pmid38792428, year = {2024}, author = {Amsterdam, D and Kupershmidt, A and Avinir, A and Matalon, R and Ohana, O and Feder, O and Shtrozberg, S and Choshen, G and Ablin, JN and Elkana, O}, title = {Long COVID-19 Enigma: Unmasking the Role of Distinctive Personality Profiles as Risk Factors.}, journal = {Journal of clinical medicine}, volume = {13}, number = {10}, pages = {}, pmid = {38792428}, issn = {2077-0383}, abstract = {Background: The COVID-19 (Coronavirus disease 2019) pandemic has prompted extensive research into lingering effects, especially in 'Long COVID' patients. Despite exploration, contributing factors remain elusive; Objective: This study explores the potential link between distinctive personality profiles, particularly type D personality, and an increased risk of Long COVID; Methods: A retrospective cross-sectional study at Tel-Aviv Sourasky Medical Center's Post-COVID clinic analyzed data from 373 Long COVID patients through comprehensive questionnaires covering Long COVID syndrome, Fibromyalgia criteria, personality assessments, social support, and subjective evaluations of cognitive decline, health and life quality. In total, 116 out of 373 patients completed the questionnaire, yielding a 31% participation rate; Results: Cluster analysis revealed two groups, with Cluster 1 (N = 58) exhibiting Type D personality traits while Cluster 2 (N = 56) not meeting criteria for Type D personality. In comparison to Cluster 2, Cluster 1 patients reported heightened anxiety, depression, reduced social support, increased pain symptoms, manifestations of fibromyalgia, cognitive decline, and poor sleep quality, contributing to a diminished quality-of-life perception; Conclusions: findings highlight diverse personality profiles among Long COVID patients, emphasizing the need for tailored care. This approach shows potential for improving Long COVID patient care, aligning with the evolving personalized medicine paradigm.}, } @article {pmid38791759, year = {2024}, author = {Gebremeskel, TG and Romeo, F and Shama, AT and Bonevski, B and Trigg, J}, title = {Facilitators and Barriers to Lung Cancer Screening during Long COVID: A Global Systematic Review and Meta-Study Synthesis of Qualitative Research.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {5}, pages = {}, pmid = {38791759}, issn = {1660-4601}, mesh = {Humans ; *Lung Neoplasms/diagnosis/psychology ; *COVID-19/psychology ; *Early Detection of Cancer/psychology ; *Qualitative Research ; SARS-CoV-2 ; }, abstract = {Background: Participation in targeted screening reduces lung cancer mortality by 30-60%, but screening is not universally available. Therefore, the study aimed to synthesize the evidence and identify facilitators and barriers to lung cancer screening participation globally. Methods: Two reviewers screened primary studies using qualitative methods published up to February 2023. We used two-phase synthesis consistent with a meta-study methodology to create an interpretation of lung cancer screening decisions grounded in primary studies, carried out a thematic analysis of group themes as specific facilitators and barriers, systematically compared investigations for similarities and differences, and performed meta-synthesis to generate an expanded theory of lung cancer screening participation. We used the Social Ecological Model to organize and interpret the themes: individual, interpersonal, social/cultural, and organizational/structural levels. Results: Fifty-two articles met the final inclusion criteria. Themes identified as facilitating lung cancer screening included prioritizing patient education, quality of communication, and quality of provider-initiated encounter/coordination of care (individual patient and provider level), quality of the patient-provider relationship (interpersonal group), perception of a life's value and purpose (cultural status), quality of tools designed, and care coordination (and organizational level). Themes coded as barriers included low awareness, fear of cancer diagnosis, low perceived benefit, high perceived risk of low-dose computerized tomography, concern about cancer itself, practical obstacle, futility, stigma, lack of family support, COVID-19 fear, disruptions in cancer care due to COVID-19, inadequate knowledge of care providers, shared decision, and inadequate time (individual level), patient misunderstanding, poor rapport, provider recommendation, lack of established relationship, and confusing decision aid tools (interpersonal group), distrust in the service, fatalistic beliefs, and perception of aging (cultural level), and lack of institutional policy, lack of care coordinators, inadequate infrastructure, absence of insurance coverage, and costs (and organizational status). Conclusions: This study identified critical barriers, facilitators, and implications to lung cancer screening participation. Therefore, we employed strategies for a new digital medicine (artificial intelligence) screening method to balance the cost-benefit, "workdays" lost in case of disease, and family hardship, which is essential to improve lung cancer screening uptake.}, } @article {pmid38790912, year = {2024}, author = {Boruga, M and Septimiu-Radu, S and Nandarge, PS and Elagez, A and Doros, G and Lazureanu, VE and Stoicescu, ER and Tanase, E and Iacob, R and Dumitrescu, A and Bota, AV and Cotoraci, C and Bratu, ML}, title = {Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.}, journal = {Biomedicines}, volume = {12}, number = {5}, pages = {}, pmid = {38790912}, issn = {2227-9059}, abstract = {The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m[2] vs. 91.2 mL/min/1.73 m[2], p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.}, } @article {pmid38790527, year = {2024}, author = {Marcotullio, C and Attanasi, M and Porreca, A and Di Filippo, P and Matricardi, S and Venanzi, A and Schiavo, M and Paone, A and Rossi, N and Chiarelli, F and Prezioso, G}, title = {Neuropsychological Symptoms and Quality of Life during the COVID-19 Pandemic in Children: A Survey in a Pediatric Population in the Abruzzo Region, Italy.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {38790527}, issn = {2227-9067}, abstract = {BACKGROUND: The SARS-CoV-2 pandemic has significantly affected the pediatric population. Long-term sequelae (Long COVID-19) may particularly involve the central nervous system, with possible effects on psychological well-being and quality of life (QoL), aspects that were already influenced by the restrictive measures and general social impact of the pandemic.

METHODS: We conducted a cross-sectional survey that aims at investigating the neuropsychological effects and the QoL impairment of SARS-CoV-2 on a cohort of children and adolescents in the Abruzzo region (Italy). A questionnaire was submitted to caregivers with the help of the PEDIATOTEM platform. A control group of healthy subjects was also included to distinguish between the effects of infection from the general influence of the pandemic.

RESULTS: A total of 569 subjects responded: 396 COVID-19 patients (99 of whom had Long COVID-19) and 111 controls. After the pandemic, when compared with the COVID-19 group, the controls reported significantly increased appetite, sleeping habits, and time spent remotely with friends and a reduction in physical activity and time spent in person with friends. A significant higher rate of controls asked for psychological/medical support for emotional problems. On the other hand, the Long COVID-19 group showed more fatigue and emotional instability with respect to non-Long-COVID-19 subjects. No differences in QoL results (EuroQOL) were found between the COVID-19 patients and controls, while the Long-COVID-19 subgroup showed significantly higher rates of pain/discomfort and mood instability, as confirmed by the analysis of variation of responses from the pre-COVID-19 to the post-COVID-19 period.

CONCLUSIONS: Among COVID-19 patients, neuropsychological and QoL impairment was more evident in the Long COVID-19 subgroup, although emotional and relational issues were also reported by uninfected patients, with a growing request for specialist support as a possible consequence of social restriction.}, } @article {pmid38785750, year = {2024}, author = {Calcaterra, V and Zanelli, S and Foppiani, A and Verduci, E and Benatti, B and Bollina, R and Bombaci, F and Brucato, A and Cammarata, S and Calabrò, E and Cirnigliaro, G and Della Torre, S and Dell'osso, B and Moltrasio, C and Marzano, AV and Nostro, C and Romagnuolo, M and Trotta, L and Savasi, V and Smiroldo, V and Zuccotti, G}, title = {Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {38785750}, issn = {2079-9721}, abstract = {Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.}, } @article {pmid38785574, year = {2024}, author = {Lupo, R and Vitale, E and Panzanaro, L and Lezzi, A and Lezzi, P and Botti, S and Rubbi, I and Carvello, M and Calabrò, A and Puglia, A and Conte, L and De Nunzio, G}, title = {Effects of Long COVID on Psycho-Physical Conditions in the Italian Population: A Statistical and Large Language Model Combined Description.}, journal = {European journal of investigation in health, psychology and education}, volume = {14}, number = {5}, pages = {1153-1170}, pmid = {38785574}, issn = {2254-9625}, abstract = {BACKGROUND: Long COVID refers to the persistence or development of signs and symptoms well after the acute phase of COVID-19.

OBJECTIVE OF THE STUDY: To investigate the long-term outcomes of the SARS-CoV-2 infection in terms of psychological, social, and relational consequences within the Italian population.

MATERIALS AND METHODS: We conducted an observational, cross-sectional, and multicenter study using an online questionnaire distributed to a sample of the Italian population. By utilizing the Short Form 12 Health Survey (SF-12) and the Hikikomori scale, we assessed perceived quality of life and social isolation, respectively. The questionnaire also included an open-answer question: "What will you remember about the pandemic period?". We used generative artificial intelligence to analyze and summarize the corresponding answers.

RESULTS: A total of 1097 people participated in this study. A total of 79.3% (n = 870) of participants declared that they had been hospitalized and 62.8% (n = 689) received home care. Physical symptoms included headaches (43%, n = 472) and asthma (30.4%, n = 334). Additionally, 29.2% (n = 320) developed an addiction during the pandemic and, among these, 224 claimed internet addiction while 73 declared an emotional addiction. Furthermore, 51.8% (n = 568) experienced limitations in carrying out daily life activities. According to the Hikikomori scale, participants with positive SARS-CoV-2 infection exhibited higher levels of isolation compared to the others (p < 0.001). Participants without COVID-19 showed higher levels of emotional support (p < 0.001). Our semiautomatic analysis of the open-ended responses, obtained by a procedure based on a free large language model, allowed us to deduce and summarize the main feelings expressed by the interviewees regarding the pandemic.

CONCLUSIONS: The data collected emphasize the urgent need to investigate the consequences of long COVID in order to implement interventions to support psychological well-being.}, } @article {pmid38785545, year = {2024}, author = {Vavougios, GD and Mavridis, T and Doskas, T and Papaggeli, O and Foka, P and Hadjigeorgiou, G}, title = {SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer's Disease.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {4565-4579}, pmid = {38785545}, issn = {1467-3045}, support = {COVALENT and COGNATE studies (No grant number applicable)//Cyprus Academy of Letters and Arts/ ; }, abstract = {Type I interferon signaling (IFN-I) perturbations are major drivers of COVID-19. Dysregulated IFN-I in the brain, however, has been linked to both reduced cognitive resilience and neurodegenerative diseases such as Alzheimer's. Previous works from our group have proposed a model where peripheral induction of IFN-I may be relayed to the CNS, even in the absence of fulminant infection. The aim of our study was to identify significantly enriched IFN-I signatures and genes along the transolfactory route, utilizing published datasets of the nasal mucosa and olfactory bulb amygdala transcriptomes of COVID-19 patients. We furthermore sought to identify these IFN-I signature gene networks associated with Alzheimer's disease pathology and risk. Gene expression data involving the nasal epithelium, olfactory bulb, and amygdala of COVID-19 patients and transcriptomic data from Alzheimer's disease patients were scrutinized for enriched Type I interferon pathways. Gene set enrichment analyses and gene-Venn approaches were used to determine genes in IFN-I enriched signatures. The Agora web resource was used to identify genes in IFN-I signatures associated with Alzheimer's disease risk based on its aggregated multi-omic data. For all analyses, false discovery rates (FDR) <0.05 were considered statistically significant. Pathways associated with type I interferon signaling were found in all samples tested. Each type I interferon signature was enriched by IFITM and OAS family genes. A 14-gene signature was associated with COVID-19 CNS and the response to Alzheimer's disease pathology, whereas nine genes were associated with increased risk for Alzheimer's disease based on Agora. Our study provides further support to a type I interferon signaling dysregulation along the extended olfactory network as reconstructed herein, ranging from the nasal epithelium and extending to the amygdala. We furthermore identify the 14 genes implicated in this dysregulated pathway with Alzheimer's disease pathology, among which HLA-C, HLA-B, HLA-A, PSMB8, IFITM3, HLA-E, IFITM1, OAS2, and MX1 as genes with associated conferring increased risk for the latter. Further research into its druggability by IFNb therapeutics may be warranted.}, } @article {pmid38784593, year = {2024}, author = {Collins, E and Galipeau, Y and Arnold, C and Bhéreur, A and Booth, R and Buchan, AC and Cooper, C and Crawley, AM and McCluskie, PS and McGuinty, M and Pelchat, M and Rocheleau, L and Saginur, R and Gravel, C and Hawken, S and Langlois, MA and Little, J}, title = {Clinical and serological predictors of post COVID-19 condition-findings from a Canadian prospective cohort study.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1276391}, pmid = {38784593}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology/immunology/blood/diagnosis ; Male ; Female ; Prospective Studies ; Middle Aged ; Canada/epidemiology ; *Immunoglobulin G/blood ; *SARS-CoV-2/immunology ; Adult ; Antibodies, Viral/blood ; Aged ; Risk Factors ; Biomarkers/blood ; Post-Acute COVID-19 Syndrome ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {INTRODUCTION: More than 3 years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates.

METHODS: We compared clinical and serological predictors among COVID-19 survivors with (n = 102 cases) and without (n = 122 controls) persistent symptoms ≥12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori.

RESULTS: Similar proportions of PCC-cases (66.7%, n = 68) and infected-controls (71.3%, n = 87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n = 96) and anti-RBD (95.1%, n = 97) IgG, as compared with controls (anti-Spike: 89.3%, n = 109; anti-RBD: 84.4%, n = 103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11-4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64-7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p = 0.02), number of months post COVID-19 (OR 1.1, p < 0.01), allergies (OR 1.8, p = 0.04), and need for medical support (OR 4.1, p < 0.01).

CONCLUSION: Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings.}, } @article {pmid38784592, year = {2024}, author = {Gelhorn, HL and Ghafoori, P and Cutts, K and Birch, H and Savva, Y and Satram, S and Lloyd, E and Chen, WH}, title = {Characterizing health-related quality of life and identifying disease predictors among patients suspected of having long COVID: an analysis of COMET-ICE clinical trial data.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1278106}, pmid = {38784592}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; *Quality of Life ; Male ; Female ; Middle Aged ; Aged ; SARS-CoV-2 ; Adult ; Surveys and Questionnaires ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {INTRODUCTION: Long COVID affects health-related quality of life (HRQoL). Here, we investigate the extent to which symptoms experienced during the acute phase of COVID-19 are significant predictors of the presence of long COVID at 12 weeks.

METHODS: Post-hoc analysis of COMET-ICE trial data, which assessed sotrovimab vs. placebo for treatment of mild-to-moderate COVID-19 among high-risk patients. Patient-reported outcome measures were completed during the trial, including the inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus), the 12-Item Short Form (SF-12) Hybrid questionnaire, and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH). COVID-19 symptoms and impacts (measured by the FLU-PRO Plus) and HRQoL (measured by SF-12 Hybrid and WPAI:GH) were compared between the acute phase (Days 1-21 and 29) and long-COVID phase (at Week 12) among patients with and without long COVID based on COMET-ICE data. Subgroups experiencing long COVID were derived using "All," "Returning," and "Persisting" symptomatic definitions. Long-COVID predictors were identified using a multivariate logistic regression model; odds ratios (ORs) and 95% CIs were calculated.

RESULTS: Long-COVID subgroups had significantly higher baseline scores for most FLU-PRO Plus domains and Total Score compared with the non-long-COVID group. WPAI:GH and SF-12 Hybrid scores generally showed significantly more impairment for the long-COVID subgroups at baseline and Week 12 vs. the non-long-COVID group. In the univariate analyses, all FLU-PRO Plus domains were significant predictors of long COVID (all p < 0.05), with the exception of the Sense domain. Older age increased the risk of long COVID (OR 1.02, 95% CI 1.00-1.04, p < 0.05). Non-White patients were significantly less likely to have long COVID by the Returning and Persisting definitions vs. White patients (all p < 0.05). In the multivariate analysis, higher scores for the Nose domain (ORs 3.39-5.60, all p < 0.01) and having COPD (ORs 3.75-6.34, all p < 0.05) were significant long-COVID predictors.

CONCLUSION: Patients who progressed to long COVID had higher symptom severity during the acute disease phase and showed significantly greater negative impact on HRQoL over an extended time period from initial infection through at least the subsequent 3 months. The FLU-PRO Plus Nose domain and having COPD were significant predictors of long COVID.}, } @article {pmid38783782, year = {2024}, author = {Jones, F and Domeny, A and Fish, J and Leggat, F and Patel, I and McRae, J and Rowe, C and Busse, ME}, title = {Using co-design methods to develop new personalised support for people living with Long Covid: The 'LISTEN' intervention.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {3}, pages = {e14093}, pmid = {38783782}, issn = {1369-7625}, support = {Listen COV-LT2-0009//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/therapy ; *Self-Management/methods ; Female ; Male ; SARS-CoV-2 ; Middle Aged ; Adult ; United Kingdom ; Survivors/psychology ; Aged ; }, abstract = {INTRODUCTION: Many Covid-19 survivors are living with unresolved, relapsing and remitting symptoms and no 'one size' of treatment is likely to be effective for everyone. Supported self-management for the varied symptoms of Long Covid (LC) is recommended by the National Institute for Health and Care Excellence in the United Kingdom. We aimed to develop a new personalised support intervention for people living with LC using a structured co-design framework to guide replication and evaluation.

METHODS: We used the improvement methodology, Experience-Based Co-Design, in an accelerated form to harness the collective experiences of people with LC. Incorporating evidence from 'Bridges Self-Management' (Bridges) an approach in which healthcare professionals (HCPs)are trained to support knowledge, confidence and skills of individuals living with long term conditions. Co-designed resources are also central to Bridges. Adults who self-identified as living with or recovered from LC, from England or Wales, aged 18 years and over were recruited, and HCPs, with experience of supporting people with LC. Participants took part in a series of small co-design group meetings and larger mixed meetings to agree priorities, core principles and generate resources and intervention content.

RESULTS: People with LC (n = 28), and HCPs (n = 9) supported co-design of a book (hard-copy and digital form) to be used in 1:1 support sessions with a trained HCP. Co-design stages prioritised stories about physical symptoms first, and psychological and social challenges which followed, nonlinear journeys and reconceptualising stability as progress, rich descriptions of strategies and links to reputable advice and support for navigating healthcare services. Co-design enabled formulation of eight core intervention principles which underpinned the training and language used by HCPs and fidelity assessments.

CONCLUSION: We have developed a new personalised support intervention, with core principles to be used in one-to-one sessions delivered by trained HCPs, with a new co-designed book as a prompt to build personalised strategies and plans using narratives, ideas, and solutions from other people with LC. Effectiveness and cost effectiveness of the 'LISTEN' intervention will be evaluated in a randomised controlled trial set within the context of the updated Framework for Developing and Evaluating Complex Interventions.

The LISTEN Public and Patient Involvement (PPI) group comprised seven people living with LC. They all contributed to the design of this study and five members were part of a larger co-design community described in this paper. They have contributed to this paper by interpreting stages of intervention design and analysis of results. Three members of our PPI group are co-authors of this paper.}, } @article {pmid38782998, year = {2024}, author = {Rinaldi, L and Rigo, S and Pani, M and Bisoglio, A and Khalaf, K and Minonzio, M and Shiffer, D and Romeo, MA and Verzeletti, P and Ciccarelli, M and Bordoni, MG and Stranges, S and Riboli, E and Furlan, R and Barbic, F}, title = {Long-COVID autonomic syndrome in working age and work ability impairment.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11835}, pmid = {38782998}, issn = {2045-2322}, mesh = {Humans ; Male ; Middle Aged ; Female ; *COVID-19/complications/physiopathology/epidemiology/virology ; Prospective Studies ; Italy/epidemiology ; Adult ; SARS-CoV-2/isolation & purification ; Autonomic Nervous System Diseases/physiopathology/epidemiology ; Post-Acute COVID-19 Syndrome ; Return to Work ; Autonomic Nervous System/physiopathology ; Surveys and Questionnaires ; }, abstract = {Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.}, } @article {pmid38782355, year = {2024}, author = {Ramonfaur, D and Ayad, N and Liu, PHZ and Zhou, J and Wu, Y and Li, J and Chen, G}, title = {The global clinical studies of long COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {146}, number = {}, pages = {107105}, doi = {10.1016/j.ijid.2024.107105}, pmid = {38782355}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; Global Health ; COVID-19 Drug Treatment ; United States/epidemiology ; }, abstract = {People with long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions-31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guidelines for its treatment. With more and more nationwide projects funded by the government such as the RECOVER initiative in the United States and National Institute for Health Research funding in the United Kingdom, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the World Health Organization International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduced cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative, unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking.}, } @article {pmid38782246, year = {2024}, author = {Palacio, A and Bast, E and Klimas, N and Tamariz, L}, title = {Lessons Learned in Implementing a Multidisciplinary Long COVID Clinic.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.05.020}, pmid = {38782246}, issn = {1555-7162}, abstract = {The diagnosis and treatment of long COVID patients is challenging. Our aim is to share lessons learned using a multidisciplinary approach within the Veterans Affairs system. Our long COVID clinic is based in primary care but has imbedded rehabilitation specialists, nutrition, whole health, and different specialists within internal medicine. We conducted an extensive work-up to evaluate the presence of end-organ damage, ongoing inflammation, and dysautonomia. Our treatments are based on the prior experience that the Veterans Affairs system has on chronic fatigue syndrome and gulf war illness.}, } @article {pmid38779550, year = {2024}, author = {Tunnell, NC and Corner, SE and Roque, AD and Kroll, JL and Ritz, T and Meuret, AE}, title = {Biobehavioral approach to distinguishing panic symptoms from medical illness.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1296569}, pmid = {38779550}, issn = {1664-0640}, abstract = {Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.}, } @article {pmid38778362, year = {2024}, author = {Santos, JV and Padron-Monedero, A and Bikbov, B and Grad, DA and Plass, D and Mechili, EA and Gazzelloni, F and Fischer, F and Sulo, G and Ngwa, CH and Noguer-Zambrano, I and Peñalvo, JL and Haagsma, JA and Kissimova-Skarbek, K and Monasta, L and Ghith, N and Sarmiento-Suarez, R and Hrzic, R and Haneef, R and O'Caoimh, R and Cuschieri, S and Mondello, S and Kabir, Z and , and Freitas, A and Devleesschauwer, B}, title = {The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {1374}, pmid = {38778362}, issn = {1471-2458}, mesh = {Humans ; *European Union/statistics & numerical data ; *Global Burden of Disease/trends ; *Life Expectancy/trends ; *Disability-Adjusted Life Years/trends ; Male ; Health Status ; Female ; Cost of Illness ; }, abstract = {BACKGROUND: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010.

METHODS: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE).

RESULTS: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%).

CONCLUSIONS: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.}, } @article {pmid38777281, year = {2024}, author = {Boruch, AE and Barhorst, EE and Rayne, TJ and Roberge, GA and Brukardt, SM and Leitel, ZT and Coe, CL and Fleshner, M and Falvo, MJ and Cook, DB and Lindheimer, JB}, title = {Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose-response, crossover study.}, journal = {Brain, behavior, and immunity}, volume = {120}, number = {}, pages = {221-230}, pmid = {38777281}, issn = {1090-2139}, support = {IK2 CX001679/CX/CSRD VA/United States ; P51 OD011106/OD/NIH HHS/United States ; }, mesh = {Humans ; *Cross-Over Studies ; Male ; *Persian Gulf Syndrome ; *Veterans ; Middle Aged ; *Exercise/physiology ; Female ; Adult ; C-Reactive Protein/metabolism ; Cognition/physiology ; Cytokines/blood ; }, abstract = {UNLABELLED: Chronic multisymptom illnesses (CMI) such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Long-COVID, and Gulf War Illness (GWI) are associated with an elevated risk of post-exertional malaise (PEM), an acute exacerbation of symptoms and other related outcomes following exercise. These individuals may benefit from personalized exercise prescriptions which prioritize risk minimization, necessitating a better understanding of dose-response effects of exercise intensity on PEM.

METHODS: Veterans with GWI (n = 40) completed a randomized controlled crossover experiment comparing 20 min of seated rest to light-, moderate-, and vigorous-intensity cycling conditions over four separate study visits. Symptoms, pain sensitivity, cognitive performance, inflammatory markers (C-reactive protein and plasma cytokines) were measured before and within 1 h after exercise and seated rest. Physical activity behavior was measured ≥ 7 days following each study visit via actigraphy. Linear mixed effects regression models tested the central hypothesis that higher intensity exercise would elicit greater exacerbation of negative outcomes, as indicated by a significant condition-by-time interaction for symptom, pain sensitivity, cognitive performance, and inflammatory marker models and a significant main effect of condition for physical activity models.

RESULTS: Significant condition-by-time interactions were not observed for primary or secondary measures of symptoms, pain sensitivity, cognitive performance, and a majority of inflammatory markers. Similarly, a significant effect of condition was not observed for primary or secondary measures of physical activity.

CONCLUSIONS: Undesirable effects such as symptom exacerbation were observed for some participants, but the group-level risk of PEM following light-, moderate-, or vigorous-intensity exercise was no greater than seated rest. These findings challenge several prior views about PEM and lend support to a broader body of literature showing that the benefits of exercise outweigh the risks.}, } @article {pmid38776716, year = {2024}, author = {Svensson Akusjärvi, S and Zanoni, I}, title = {Yin and yang of interferons: lessons from the coronavirus disease 2019 (COVID-19) pandemic.}, journal = {Current opinion in immunology}, volume = {87}, number = {}, pages = {102423}, pmid = {38776716}, issn = {1879-0372}, support = {R01 DK115217/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology ; *Interferons/immunology/metabolism ; *SARS-CoV-2/immunology ; Pandemics ; Animals ; Yin-Yang ; }, abstract = {The host immune response against severe acute respiratory syndrome coronavirus 2 includes the induction of a group of natural antiviral cytokines called interferons (IFNs). Although originally recognized for their ability to potently counteract infections, the mechanistic functions of IFNs in patients with varying severities of coronavirus disease 2019 (COVID-19) have highlighted a more complex scenario. Cellular and molecular analyses have revealed that timing, location, and subtypes of IFNs produced during severe acute respiratory syndrome coronavirus 2 infection play a major role in determining disease progression and severity. In this review, we summarize what the COVID-19 pandemic has taught us about the protective and detrimental roles of IFNs during the inflammatory response elicited against a new respiratory virus across different ages and its longitudinal consequences in driving the development of long COVID-19.}, } @article {pmid38776311, year = {2024}, author = {Looker, KJ and McClenaghan, E and Judd, A and Pierotti, L and Downing, H and Phelan, J and Warren-Gash, C and Ngozi, K and Dawe, F and Relton, C and Christensen, H and Hay, AD and Mangtani, P and Nguipdop-Djomo, P and Denholm, R}, title = {Acute and long-term outcomes of SARS-CoV-2 infection in school-aged children in England: Study protocol for the joint analysis of the COVID-19 schools infection survey (SIS) and the COVID-19 mapping and mitigation in schools (CoMMinS) study.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0303892}, pmid = {38776311}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis ; Child ; England/epidemiology ; *Schools ; Adolescent ; *SARS-CoV-2/isolation & purification ; Male ; Female ; Retrospective Studies ; Risk Factors ; Case-Control Studies ; }, abstract = {BACKGROUND: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data.

AIMS: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP.

METHODS: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence.

RESULTS: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate.

CONCLUSION: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes.}, } @article {pmid38775379, year = {2024}, author = {Li, AY and Li, WX and Li, J}, title = {Emerging trends in management of long COVID with a focus on pulmonary rehabilitation: A review.}, journal = {The clinical respiratory journal}, volume = {18}, number = {5}, pages = {e13777}, pmid = {38775379}, issn = {1752-699X}, mesh = {Humans ; *COVID-19/epidemiology/rehabilitation ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Quality of Life ; Telemedicine/trends ; Dyspnea/etiology/rehabilitation ; Exercise Therapy/methods ; Critical Illness ; }, abstract = {Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.}, } @article {pmid38774424, year = {2024}, author = {Zhao, Y and Liang, Q and Jiang, Z and Mei, H and Zeng, N and Su, S and Wu, S and Ge, Y and Li, P and Lin, X and Yuan, K and Shi, L and Yan, W and Liu, X and Sun, J and Liu, W and van Wingen, G and Gao, Y and Tan, Y and Hong, Y and Lu, Y and Wu, P and Zhang, X and Wang, Y and Shi, J and Wang, Y and Lu, L and Li, X and Bao, Y}, title = {Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study.}, journal = {The Lancet regional health. Western Pacific}, volume = {47}, number = {}, pages = {101086}, pmid = {38774424}, issn = {2666-6065}, abstract = {BACKGROUND: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI).

METHODS: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated.

FINDINGS: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found.

INTERPRETATION: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection.

FUNDING: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.}, } @article {pmid38774167, year = {2024}, author = {Olumuyide, E and Agwuegbo, CC and Ahmed, EN}, title = {Exploring the Heart Failure Connection in Long COVID Patients: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e58694}, pmid = {38774167}, issn = {2168-8184}, abstract = {In this narrative review, we explore the relationship between long COVID patients and their risk of developing heart failure (HF). Patients with long COVID face a heightened risk of HF, a critical cardiovascular complication linked to the prolonged effects of COVID-19. Clinical manifestations of long COVID-associated HF present diagnostic challenges, complicating patient management. Multidisciplinary care is essential to address these complexities effectively. We found that long COVID can result in various cardiovascular issues including HF. The current view is long COVID leads to HF by activating systemic inflammation by causing endothelial dysfunction, which leads to activation of the complement pathways, tissue factor pathways, and Von Willebrand factor; activation of all these factors leads to venous and arterial thrombosis, which could lead to clogging of blood vessel of the heart leading to cardiovascular complications. The association between long COVID and HF can be challenging despite being recognized as comorbidity because biomarkers are not dependable in determining whether a patient had HF before or after contracting COVID-19. Emerging therapeutic modalities offer hope for improving outcomes, but further research is needed to refine management strategies and mitigate long-term cardiovascular consequences of COVID-19.}, } @article {pmid38773184, year = {2024}, author = {Cañas, A and Wolf, A and Mak, A and Ruddy, J and El-Sadek, S and Gomez, L and Furfaro, D and Fullilove, R and Burkart, KM and Zelnick, J and O'Donnell, MR}, title = {Racial and ethnic disparities post-hospitalization for COVID-19: barriers to access to care for survivors of COVID-19 acute respiratory distress syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11556}, pmid = {38773184}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Male ; Female ; Middle Aged ; *Healthcare Disparities ; *Health Services Accessibility ; Aged ; Adult ; *Survivors ; Retrospective Studies ; *Respiratory Distress Syndrome/therapy ; *Hospitalization/statistics & numerical data ; Cross-Sectional Studies ; New York City/epidemiology ; SARS-CoV-2 ; Ethnic and Racial Minorities ; Hispanic or Latino/statistics & numerical data ; }, abstract = {Racial and ethnic health disparities in the incidence and severity of Coronavirus Disease 2019 (COVID-19) have been observed globally and in the United States. Research has focused on transmission, hospitalization, and mortality among racial and ethnic minorities, but Long COVID-19 health disparities research is limited. This study retrospectively evaluated 195 adults who survived COVID-19 associated acute respiratory distress syndrome (C-ARDS) in New York City from March-April 2020. Among survivors, 54% met the criteria for Long COVID syndrome. Hispanic/Latinx patients, were more likely to be uninsured (p = 0.027) and were less frequently discharged to rehabilitation facilities (p < 0.001). A cross-sectional telephone survey and interview were conducted with a subset of survivors (n = 69). Among these, 11% reported a lack of follow-up primary care post-discharge and 38% had subsequent emergency room visits. Notably, 38% reported poor treatment within the health care system, with 67% attributing this to racial or ethnic bias. Thematic analysis of interviews identified four perceived challenges: decline in functional status, discrimination during hospitalization, healthcare system inequities, and non-healthcare-related structural barriers. Sources of resilience included survivorship, faith, and family support. This study highlights structural and healthcare-related barriers rooted in perceived racism and poverty as factors impacting post-COVID-19 care.}, } @article {pmid38772083, year = {2024}, author = {Silva-Passadouro, B and Tamasauskas, A and Khoja, O and Casson, AJ and Delis, I and Brown, C and Sivan, M}, title = {A systematic review of quantitative EEG findings in Fibromyalgia, Chronic Fatigue Syndrome and Long COVID.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {163}, number = {}, pages = {209-222}, doi = {10.1016/j.clinph.2024.04.019}, pmid = {38772083}, issn = {1872-8952}, mesh = {Humans ; *Fatigue Syndrome, Chronic/physiopathology/diagnosis ; *Fibromyalgia/physiopathology/diagnosis ; *COVID-19/physiopathology/complications ; *Electroencephalography/methods ; Brain/physiopathology ; }, abstract = {Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with difference in dominant symptoms in each individual. There is existing and emerging literature on possible functional alterations of the central nervous system in these conditions. This review aims to synthesise and appraise the literature on resting-state quantitative EEG (qEEG) in FMS, ME/CFS and LC, drawing on previous research on FMS and ME/CFS to help understand neuropathophysiology of the new condition LC. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Out of the initial 2510 studies identified, 17 articles were retrieved that met all the predetermined selection criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, differing to that found in ME/CFS. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns observed in FMS and ME/CFS. Our findings suggest different patterns of qEEG brainwave activity in FMS and ME/CFS. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or ME/CFS. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies tailored to each clinical syndrome.}, } @article {pmid38771423, year = {2024}, author = {Szarvas, Z and Fekete, M and Szollosi, GJ and Kup, K and Horvath, R and Shimizu, M and Tsuhiya, F and Choi, HE and Wu, HT and Fazekas-Pongor, V and Pete, KN and Cserjesi, R and Bakos, R and Gobel, O and Gyongyosi, K and Pinter, R and Kolozsvari, D and Kovats, Z and Yabluchanskiy, A and Owens, CD and Ungvari, Z and Tarantini, S and Horvath, G and Muller, V and Varga, JT}, title = {Optimizing cardiopulmonary rehabilitation duration for long COVID patients: an exercise physiology monitoring approach.}, journal = {GeroScience}, volume = {46}, number = {5}, pages = {4163-4183}, pmid = {38771423}, issn = {2509-2723}, support = {PC2022-3/2022//MTA COVID application/ ; }, mesh = {Humans ; *COVID-19/rehabilitation ; Male ; Female ; Middle Aged ; *Cardiac Rehabilitation/methods ; *Post-Acute COVID-19 Syndrome ; Aged ; Exercise Test/methods ; Quality of Life ; SARS-CoV-2 ; Exercise Therapy/methods ; }, abstract = {The presence of prolonged symptoms after COVID infection worsens the workability and quality of life. 200 adults with long COVID syndrome were enrolled after medical, physical, and mental screening, and were divided into two groups based on their performance. The intervention group (n = 100) received supervised rehabilitation at Department of Pulmonology, Semmelweis University with the registration number 160/2021 between 01/APR/2021-31/DEC/2022, while an age-matched control group (n = 100) received a single check-up. To evaluate the long-term effects of the rehabilitation, the intervention group was involved in a 2- and 3-month follow-up, carrying out cardiopulmonary exercise test. Our study contributes understanding long COVID rehabilitation, emphasizing the potential benefits of structured cardiopulmonary rehabilitation in enhancing patient outcomes and well-being. Significant difference was found between intervention group and control group at baseline visit in pulmonary parameters, as forced vital capacity, forced expiratory volume, forced expiratory volume, transfer factor for carbon monoxide, transfer coefficient for carbon monoxide, and oxygen saturation (all p < 0.05). Our follow-up study proved that a 2-week long, patient-centered pulmonary rehabilitation program has a positive long-term effect on people with symptomatic long COVID syndrome. Our data showed significant improvement between two and three months in maximal oxygen consumption (p < 0.05). Multidisciplinary, individualized approach may be a key element of a successful cardiopulmonary rehabilitation in long COVID conditions, which improves workload, quality of life, respiratory function, and status of patients with long COVID syndrome.}, } @article {pmid38771409, year = {2024}, author = {Baig, AM and Rosko, S and Jaeger, B and Gerlach, J and Rausch, H}, title = {Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols.}, journal = {Inflammopharmacology}, volume = {32}, number = {4}, pages = {2075-2090}, pmid = {38771409}, issn = {1568-5608}, mesh = {Humans ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/pathogenicity ; Genetic Predisposition to Disease ; COVID-19 Drug Treatment ; Autoimmunity ; }, abstract = {Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics.}, } @article {pmid38770235, year = {2024}, author = {Jirmanus, LZ and Valenti, RM and Griest Schwartzman, EA and Simon-Ortiz, SA and Frey, LI and Friedman, SR and Fullilove, MT}, title = {Too Many Deaths, Too Many Left Behind: A People's External Review of the U.S. Centers for Disease Control and Prevention's COVID-19 Pandemic Response.}, journal = {AJPM focus}, volume = {3}, number = {4}, pages = {100207}, pmid = {38770235}, issn = {2773-0654}, abstract = {The U.S. population has suffered worse health consequences owing to COVID-19 than comparable wealthy nations. COVID-19 had caused more than 1.1 million deaths in the U.S. as of May 2023 and contributed to a 3-year decline in life expectancy. A coalition of public health workers and community activists launched an external review of the Centers for Disease Control and Prevention's pandemic management from January 2021 to May 2023. The authors used a modified Delphi process to identify core pandemic management areas, which formed the basis for a survey and literature review. Their analysis yields 3 overarching shortcomings of the Centers for Disease Control and Prevention's pandemic management: (1) Centers for Disease Control and Prevention leadership downplays the serious impacts and aerosol transmission risks of COVID-19, (2) Centers for Disease Control and Prevention leadership has aligned public guidance with commercial and political interests over scientific evidence, and (3) Centers for Disease Control and Prevention guidance focuses on individual choice rather than emphasizing prevention and equity. Instead, the agency must partner with communities most impacted by the pandemic and encourage people to protect one another using layered protections to decrease COVID-19 transmission. Because emerging variants can already evade existing vaccines and treatments and Long COVID can be disabling and lacks definitive treatment, multifaceted, sustainable approaches to the COVID-19 pandemic are essential to protect people, the economy, and future generations.}, } @article {pmid38768621, year = {2024}, author = {Nielsen, G and Stone, J and Lee, TC and Goldstein, LH and Marston, L and Hunter, RM and Carson, A and Holt, K and Marsden, J and Le Novere, M and Nazareth, I and Noble, H and Reuber, M and Strudwick, AM and Santana Suarez, B and Edwards, MJ and , }, title = {Specialist physiotherapy for functional motor disorder in England and Scotland (Physio4FMD): a pragmatic, multicentre, phase 3 randomised controlled trial.}, journal = {The Lancet. Neurology}, volume = {23}, number = {7}, pages = {675-686}, doi = {10.1016/S1474-4422(24)00135-2}, pmid = {38768621}, issn = {1474-4465}, mesh = {Humans ; Male ; Female ; Scotland ; Middle Aged ; England ; *Physical Therapy Modalities ; Adult ; *COVID-19/epidemiology ; Aged ; Treatment Outcome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Functional motor disorder-the motor variant of functional neurological disorder-is a disabling condition that is commonly associated with poor health outcomes. Pathophysiological models have inspired new treatment approaches such as specialist physiotherapy, although evidence from large randomised controlled trials is absent. We aimed to assess the clinical effectiveness of a specialist physiotherapy intervention for functional motor disorder compared with treatment as usual.

METHODS: In this pragmatic, multicentre, phase 3 randomised controlled trial at 11 hospitals in England and Scotland, adults with a clinically definite diagnosis of functional motor disorder, diagnosed by a neurologist, were included. Participants were randomly assigned (1:1, stratified by site) using a remote web-based application to either specialist physiotherapy (a protocolised intervention of nine sessions plus follow-up) or treatment as usual (referral to local community neurological physiotherapy). Individuals working on data collection and analysis were masked to treatment allocation. The primary outcome was the physical functioning domain of the 36-item short form health questionnaire (SF36) at 12 months after randomisation. The primary analysis followed a modified intention-to-treat principle, using a complete case approach; participants who were unable to receive their randomised treatment due to the suspension of health-care services during the COVID-19 pandemic were excluded from the primary analysis. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN56136713, and is completed.

FINDINGS: Recruitment occurred between Oct 19, 2018, and March 11, 2020, pausing during the COVID-19 lockdown, and resuming from Aug 3, 2021, to Jan 31, 2022. Of 355 participants who were enrolled, 179 were randomly assigned to specialist physiotherapy and 176 to treatment as usual. 89 participants were excluded from the primary analysis due to COVID-19 interruption to treatment (27 were assigned to specialist physiotherapy and 62 to treatment as usual). After accounting for withdrawals (n=11) and loss to follow-up (n=14), the primary analysis included data from 241 participants (138 [91%] assigned specialist physiotherapy and 103 [90%] assigned treatment as usual). Physical functioning, as assessed by SF36, did not differ significantly between groups (adjusted mean difference 3·5, 95% CI -2·3 to 9·3; p=0·23). There were no serious adverse events related to the trial interventions. 35 serious adverse events were recorded in the specialist physiotherapy group by 24 participants (17·0%), and 24 serious adverse events were recorded in the treatment as usual group by 18 participants (17·0%); one death occurred in the specialist physiotherapy group (cause of death was recorded as suicide). All were considered unrelated to specialist physiotherapy.

INTERPRETATION: Although more participants who were assigned specialist physiotherapy self-rated their motor symptoms as improved and had better scores on subjective measures of mental health, the intervention did not result in better self-reported physical functioning at 12 months. Both the specialist and community neurological physiotherapy appeared to be a safe and a valued treatment for selected patients with functional motor disorder. Future research should continue to refine interventions for people with functional motor disorder and develop evidence-based methods to guide treatment triage decisions.

FUNDING: National Institute for Health and Care Research and Health Technology Assessment Programme.}, } @article {pmid38768458, year = {2024}, author = {Chou, R and Herman, E and Ahmed, A and Anderson, J and Selph, S and Dana, T and Williams, L and Ivlev, I}, title = {Long COVID Definitions and Models of Care : A Scoping Review.}, journal = {Annals of internal medicine}, volume = {177}, number = {7}, pages = {929-940}, doi = {10.7326/M24-0677}, pmid = {38768458}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Terminology as Topic ; Delivery of Health Care/organization & administration ; }, abstract = {BACKGROUND: Definitions of long COVID are evolving, and optimal models of care are uncertain.

PURPOSE: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models.

DATA SOURCES: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants.

STUDY SELECTION: Publications describing long COVID definitions or models of care, supplemented by models described by key informants.

DATA EXTRACTION: Data were extracted by one reviewer and verified for accuracy by another reviewer.

DATA SYNTHESIS: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified.

LIMITATIONS: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models.

CONCLUSION: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models.

PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).}, } @article {pmid38768451, year = {2024}, author = {}, title = {Annals Video Summary - Long COVID Definitions and Models of Care: A Scoping Review.}, journal = {Annals of internal medicine}, volume = {177}, number = {7}, pages = {eM240874}, doi = {10.7326/M24-0874}, pmid = {38768451}, issn = {1539-3704}, } @article {pmid38768449, year = {2024}, author = {Brode, WM}, title = {Long COVID: The Enduring Pandemic.}, journal = {Annals of internal medicine}, volume = {177}, number = {7}, pages = {978-979}, doi = {10.7326/M24-0879}, pmid = {38768449}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; *Pandemics ; }, } @article {pmid38768246, year = {2024}, author = {Connor, C and Taylor, HA}, title = {The Importance of Including Long COVID Outcomes When Developing Novel Treatments for Acute COVID-19.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {4}, pages = {789-796}, doi = {10.1093/infdis/jiae270}, pmid = {38768246}, issn = {1537-6613}, support = {//Intramural Research Program of the Clinical Center/ ; //National Institutes of Health./ ; }, mesh = {Humans ; *COVID-19/therapy ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Treatment Outcome ; Hospitalization ; Clinical Trials as Topic ; }, abstract = {Amid efforts to develop effective treatments for acute COVID-19, there is growing recognition of the need to address long COVID as a key outcome measure. We argue there are 7 compelling reasons to include long COVID measurements in clincal trials investigating acute COVID-19 treatments: (1) Long COVID is not rare. (2) Long COVID is debilitating to individuals and has a high societal cost. (3) Those at high risk of severe COVID-19 are also at higher risk of developing long COVID if they are infected with COVID-19. (4) Treatments for acute COVID-19 may reduce the risk of long COVID. (5) Measures exist to track long COVID. (6) Long COVID considerations are potentially important for acute COVID-19 treatment decision making. (7) Deaths and hospitalizations due to COVID-19 are increasingly rare. While not every trial needs to include assessments of long COVID, it is worth the research burden to include assessments where possible, as this could facilitate the uptake of acute COVID-19 treatments that lessen the societal burden of long COVID.}, } @article {pmid38767144, year = {2024}, author = {Akanchise, T and Angelov, B and Angelova, A}, title = {Nanomedicine-mediated recovery of antioxidant glutathione peroxidase activity after oxidative-stress cellular damage: Insights for neurological long COVID.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, pages = {e29680}, doi = {10.1002/jmv.29680}, pmid = {38767144}, issn = {1096-9071}, support = {//European Regional Development Fund/ ; //European Commission/ ; }, mesh = {Humans ; *Antioxidants/pharmacology ; COVID-19/metabolism ; *COVID-19 Drug Treatment ; *Ginkgolides/pharmacology ; *Glutathione Peroxidase/drug effects/metabolism ; Lactones/pharmacology ; *Nanomedicine/methods ; *Nanoparticles ; Neurons/drug effects/virology ; *Oxidative Stress/drug effects ; Quercetin/pharmacology ; Reactive Oxygen Species/metabolism ; SARS-CoV-2/drug effects ; *Post-Acute COVID-19 Syndrome/drug therapy/metabolism ; }, abstract = {Nanomedicine for treating post-viral infectious disease syndrome is at an emerging stage. Despite promising results from preclinical studies on conventional antioxidants, their clinical translation as a therapy for treating post-COVID conditions remains challenging. The limitations are due to their low bioavailability, instability, limited transport to the target tissues, and short half-life, requiring frequent and high doses. Activating the immune system during coronavirus (SARS-CoV-2) infection can lead to increased production of reactive oxygen species (ROS), depleted antioxidant reserve, and finally, oxidative stress and neuroinflammation. To tackle this problem, we developed an antioxidant nanotherapy based on lipid (vesicular and cubosomal types) nanoparticles (LNPs) co-encapsulating ginkgolide B and quercetin. The antioxidant-loaded nanocarriers were prepared by a self-assembly method via hydration of a lyophilized mixed thin lipid film. We evaluated the LNPs in a new in vitro model for studying neuronal dysfunction caused by oxidative stress in coronavirus infection. We examined the key downstream signaling pathways that are triggered in response to potassium persulfate (KPS) causing oxidative stress-mediated neurotoxicity. Treatment of neuronally-derived cells (SH-SY5Y) with KPS (50 mM) for 30 min markedly increased mitochondrial dysfunction while depleting the levels of both glutathione peroxidase (GSH-Px) and tyrosine hydroxylase (TH). This led to the sequential activation of apoptotic and necrotic cell death processes, which corroborates with the crucial implication of the two proteins (GSH-Px and TH) in the long-COVID syndrome. Nanomedicine-mediated treatment with ginkgolide B-loaded cubosomes and vesicular LNPs showed minimal cytotoxicity and completely attenuated the KPS-induced cell death process, decreasing apoptosis from 32.6% (KPS) to 19.0% (MO-GB), 12.8% (MO-GB-Quer), 14.8% (DMPC-PEG-GB), and 23.6% (DMPC-PEG-GB-Quer) via free radical scavenging and replenished GSH-Px levels. These findings indicated that GB-LNPs-based nanomedicines may protect against KPS-induced apoptosis by regulating intracellular redox homeostasis.}, } @article {pmid38766576, year = {2023}, author = {Köseoğlu, BF and Sonel Tur, B and Kutay Ordu Gökkaya, N and Güneş Gökmen, İ and Nur Kesiktaş, F and Bilir Kaya, B and Önal, R and Tuncay, F and Genç, A and Findikoglu, G and Koldaş Doğan, Ş and Tomruk Sütbeyaz, S and Sarıkaya, S and Tıkız, C and Özdemir, H and Demirbağ Kabayel, D and Örücü Atar, M and Atan, T and Yüksel, S}, title = {Applying the WHO ICF framework to long COVID patients with persistent respiratory symptoms.}, journal = {Turkish journal of physical medicine and rehabilitation}, volume = {69}, number = {4}, pages = {410-423}, pmid = {38766576}, issn = {2587-1250}, abstract = {OBJECTIVES: The aim of this study was to evaluate long COVID patients with persistent respiratory symptoms through the application of the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) framework.

PATIENTS AND METHODS: This national, prospective, multicenter, cross-sectional study was conducted with 213 patients (118 females, 95 males; median age 56 years; range, 20 to 85 years) with long COVID between February 2022 and November 2022. The ICF data were primarily collected through patient interviews and from the acute medical management records, physical examination findings, rehabilitation outcomes, and laboratory test results. Each parameter was linked to the Component Body Functions (CBF), the Component Body Structures (CBS), the Component Activities and Participation (CAP), the Component Environmental Factors (CEF), and Personal Factors according to the ICF linking rules. Analysis was made of the frequency of the problems encountered at each level of ICF category and by what percentage of the patient sample.

RESULTS: In the ICF, 21 categories for CBF, 1 category for CBS, and 18 categories of CAP were reported as a significant problem in a Turkish population of long COVID patients with persistent respiratory symptoms. Furthermore, eight categories for CEF were described as a facilitator, and four as a barrier.

CONCLUSION: These results can be of guidance and provide insight into the identification of health and health-related conditions of long COVID patients with persistent respiratory symptoms beyond the pathophysiological aspects, organ involvement, and damage of COVID-19. The ICF can be used in patients with long COVID to describe the types and magnitude of impairments, restrictions, special needs, and complications.}, } @article {pmid38766119, year = {2024}, author = {Duque-Wilckens, N and Maradiaga, N and Szu-Ying, Y and Joseph, D and Srinavasan, V and Thelen, K and Sotomayor, F and Durga, K and Nestler, E and Moeser, AJ and Robison, AJ}, title = {Activity-dependent FosB gene expression negatively regulates mast cell functions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.06.592755}, pmid = {38766119}, issn = {2692-8205}, abstract = {Mast cells are innate immune cells that play a crucial role in numerous physiological processes across tissues by releasing pre-stored and newly synthesized mediators in response to stimuli, an activity largely driven by changes in gene expression. Given their widespread influence, dysfunction in mast cells can contribute to a variety of pathologies including allergies, long COVID, and autoimmune and neuroinflammatory disorders. Despite this, the specific transcriptional mechanisms that control mast cell mediator release remain poorly understood, significantly hindering the development of effective therapeutic strategies. We found that the two proteins encoded by the transcription factor FosB, FOSB and the highly stable variant ΔFOSB, are robustly expressed upon stimulation in both murine and human mast cell progenitors. Motivated by these findings, we generated a novel mouse model with targeted ablation of FosB gene expression specifically in mast cells (MC [FosB-]) by crossing a mast cell-specific Cre reporter line (Mcpt5-Cre) with a Cre-dependent floxed FosB mouse lines. We found that mast cell progenitors derived from MC [FosB-] mice, compared to wild types (WT), exhibit baseline increased histamine content and vesicle numbers. Additionally, they show enhanced calcium mobilization, degranulation, and histamine release following allergy-related IgE-mediated stimulation, along with heightened IL-6 release in response to infection-like LPS stimulation. In vivo experiments with IgE- mediated and LPS challenges revealed that MC [FosB-] mice experience greater drops in body temperature, heightened activation of tissue-resident mast cells, and increased release of pro-inflammatory mediators compared to their WT counterparts. These findings suggest that FosB products play a crucial regulatory role in moderating stimulus-induced mast cell activation in response to both IgE and LPS stimuli. Lastly, by integrating CUT&RUN and RNAseq data, we identified several genes targeted by ΔFOSB that could mediate these observed effects, including Mir155hg, CLCF1, DUSP4, and Trib1. Together, this study provides the first evidence that FOSB/ΔFOSB modulate mast cell functions and provides a new possible target for therapeutic interventions aimed at ameliorating mast cell-related diseases.}, } @article {pmid38765222, year = {2024}, author = {Kalinowski, J and Hintz, EA and Izeogu, C}, title = {The Untapped Power of "We Don't Know": Epistemological Humility in the Era of COVID-19.}, journal = {Journal of patient experience}, volume = {11}, number = {}, pages = {23743735241252475}, pmid = {38765222}, issn = {2374-3735}, abstract = {The SARS-CoV-2 (COVID-19) pandemic introduced many challenges and nuances that have transformed medical practice and research. The uncertainty caused by COVID-19 led to inevitable challenges to patient-provider relationships. The ever-changing landscape of COVID-19 research and policy proved to be challenging for the medical community and patients. These challenges also exacerbated long-standing issues regarding patient-provider communication and trust. On the other hand, these challenges gave voice to a burgeoning patient advocacy community. Through social media, advocacy and patient organizing, patients harnessed their power and organized over challenges relating to COVID-19 fears and concerns, ramifications of "Long COVID," and much more. During this unprecedented pandemic, there was a realization that the science and research surrounding COVID-19 is evolving and that there may be a benefit to embracing the dynamic nature of research and the scientific process. We propose that providers and the medical community should consider epistemological humility, which acknowledges insufficiencies related to the state of medical knowledge with a sense of understanding and respect for not having all of the answers. We argue that there is untapped potential in saying, "We don't know" and explaining why. There is an implicit culture that providers should be responsible for knowing everything and solving every problem. Epistemological humility challenges this culture, and inherently gives credence and voice to patient perspectives. We assert that epistemological humility is necessity when addressing contemporary health challenges such as COVID-19.}, } @article {pmid38765079, year = {2024}, author = {Ho, WY and Shen, ZH and Chen, Y and Chen, TH and Lu, X and Fu, YS}, title = {Therapeutic implications of quercetin and its derived-products in COVID-19 protection and prophylactic.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30080}, pmid = {38765079}, issn = {2405-8440}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, which has triggered a global pandemic of the coronavirus infectious disease 2019 (COVID-19). Outbreaks of emerging infectious diseases continue to challenge human health worldwide. The virus conquers human cells through the angiotensin-converting enzyme 2 receptor-driven pathway by mostly targeting the human respiratory tract. Quercetin is a natural flavonoid widely represented in the plant kingdom. Cumulative evidence has demonstrated that quercetin and its derivatives have various pharmacological properties including anti-cancer, anti-hypertension, anti-hyperlipidemia, anti-hyperglycemia, anti-microbial, antiviral, neuroprotective, and cardio-protective effects, because it is a potential treatment for severe inflammation and acute respiratory distress syndrome. Furthermore, it is the main life-threatening condition in patients with COVID-19. This article provides a comprehensive review of the primary literature on the predictable effectiveness of quercetin and its derivatives docked to multi-target of SARS-CoV-2 and host cells via in silico and some of validation through in vitro, in vivo, and clinically to fight SARS-CoV-2 infections, contribute to the reduction of inflammation, which suggests the preventive and therapeutic latency of quercetin and its derived-products against COVID-19 pandemic, multisystem inflammatory syndromes (MIS), and long-COVID.}, } @article {pmid38765011, year = {2024}, author = {Sasso, EM and Muraki, K and Eaton-Fitch, N and Smith, P and Jeremijenko, A and Griffin, P and Marshall-Gradisnik, S}, title = {Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1264702}, pmid = {38765011}, issn = {1664-3224}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/immunology ; COVID-19 Drug Treatment ; Fatigue Syndrome, Chronic/drug therapy/immunology ; Killer Cells, Natural/immunology/metabolism ; Naltrexone/pharmacology/therapeutic use ; Patch-Clamp Techniques ; SARS-CoV-2/physiology ; *TRPM Cation Channels/metabolism ; }, abstract = {INTRODUCTION: Recently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.

METHODS: Whole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol.

RESULTS: This investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.

DISCUSSION: Our findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca[2+]) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.}, } @article {pmid38765009, year = {2024}, author = {Singh, A and Adam, A and Aditi, and Peng, BH and Yu, X and Zou, J and Kulkarni, VV and Kan, P and Jiang, W and Shi, PY and Samir, P and Cisneros, I and Wang, T}, title = {A murine model of post-acute neurological sequelae following SARS-CoV-2 variant infection.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1384516}, pmid = {38765009}, issn = {1664-3224}, support = {R01 AI176670/AI/NIAID NIH HHS/United States ; R01 NS125778/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; Mice ; *Disease Models, Animal ; *Post-Acute COVID-19 Syndrome ; Humans ; Brain/virology/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood/immunology ; Angiotensin-Converting Enzyme 2/genetics/metabolism ; Female ; }, abstract = {Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.}, } @article {pmid38763165, year = {2024}, author = {Spiesshoefer, J and Regmi, B and Senol, M and Jörn, B and Gorol, O and Elfeturi, M and Walterspacher, S and Giannoni, A and Kahles, F and Gloeckl, R and Dreher, M}, title = {Potential Diaphragm Muscle Weakness-related Dyspnea Persists 2 Years after COVID-19 and Could Be Improved by Inspiratory Muscle Training: Results of an Observational and an Interventional Clinical Trial.}, journal = {American journal of respiratory and critical care medicine}, volume = {210}, number = {5}, pages = {618-628}, pmid = {38763165}, issn = {1535-4970}, support = {//RWTH Aachen Faculty of Medicine/United States ; }, mesh = {Humans ; Male ; Female ; *Dyspnea/physiopathology/therapy/etiology ; Middle Aged ; *COVID-19/complications/physiopathology/therapy ; *Muscle Weakness/physiopathology/therapy/etiology ; *Diaphragm/physiopathology ; *Breathing Exercises/methods ; Respiratory Muscles/physiopathology ; SARS-CoV-2 ; }, abstract = {Rationale: Diaphragm muscle weakness might underlie persistent exertional dyspnea, despite normal lung and cardiac function in individuals who were previously hospitalized for acute coronavirus disease (COVID-19) illness. Objectives: The authors sought, first, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea 2 years after hospitalization for COVID-19 and, second, to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. Methods: Approximately 2 years after hospitalization for COVID-19, 30 individuals (11 women, 19 men; median age, 58 years; interquartile range [IQR] = 51-63) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT. Measurements and Main Results: At a median of 31 months (IQR = 23-32) after hospitalization, 21 of 30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure, 83 cm H2O [IQR = 75-91] vs. 100 cm H2O [IQR = 81-113], P = 0.02), inspiratory muscle fatiguability (time to task failure, 365 s [IQR = 284-701] vs. 983 s [IQR = 551-1,494], P = 0.05), diaphragm voluntary activation index (79% [IQR = 63-92] vs. 89% [IQR = 75-94], P = 0.03), and dyspnea (Borg score, 7 [IQR = 5.5-8] vs. 6 [IQR = 4-7], P = 0.03). Improvements persisted for 6 weeks after IMT completion. Conclusions: To the best of the authors' knowledge, this study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID and provide a possible pathophysiological explanation for the treatment benefit. Clinical trial registered with www.clinicaltrials.gov (NCT04854863, NCT05582642).}, } @article {pmid38762902, year = {2024}, author = {Rivas-Vazquez, RA and Carrazana, EJ and Rivas-Vazquez, EV and Quintana, A}, title = {Growing Evidence for Potential Use of Antidepressants for Long COVID.}, journal = {The primary care companion for CNS disorders}, volume = {26}, number = {3}, pages = {}, doi = {10.4088/PCC.23lr03690}, pmid = {38762902}, issn = {2155-7780}, mesh = {Humans ; *Antidepressive Agents/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38762206, year = {2024}, author = {Ford, ND and Slaughter, D and Dalton, AF and Edwards, D and Ma, K and King, H and Saydah, S}, title = {Health Insurance and Access to Care in U.S. Working-Age Adults Experiencing Long COVID.}, journal = {American journal of preventive medicine}, volume = {67}, number = {4}, pages = {530-539}, doi = {10.1016/j.amepre.2024.05.007}, pmid = {38762206}, issn = {1873-2607}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Adult ; *Health Services Accessibility/statistics & numerical data ; Middle Aged ; Male ; United States ; Female ; *Insurance, Health/statistics & numerical data ; *Insurance Coverage/statistics & numerical data ; Young Adult ; Adolescent ; Medically Uninsured/statistics & numerical data ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID encompasses a wide range of health problems that emerge, persist, or recur following acute coronavirus disease 2019 (COVID-19) illness. Given that the prevalence of self-reported Long COVID is highest among U.S. adults in their prime working years, it is important to identify unmet needs and gaps in healthcare access and coverage among working-age adults.

METHODS: Prevalences (95% confidence intervals [CI]) of health insurance coverage and access to care by Long COVID status were estimated among adults 18-64 years (n=18,117), accounting for survey design and weighted to the U.S. non-institutionalized population in the 2022 National Health Interview Survey. Analyses were conducted in 2023.

RESULTS: Overall, 3.7% (95% CI 3.4, 4.0) of respondents were experiencing Long COVID. Adults experiencing Long COVID were less likely to report being uninsured relative to adults not experiencing Long COVID (p=0.004); however, 49.0% (95% CI 43.2, 54.7) had high deductible health plans. Adjusting for sociodemographic characteristics, adults experiencing Long COVID were more likely to access healthcare compared to adults not experiencing Long COVID (p<0.01 for seeing a doctor, telemedicine appointments, ≥2 urgent care visits, ≥2 emergency department visits, and hospitalized overnight). Despite more frequent healthcare use, adults experiencing Long COVID were also more likely to abstain from and delay medical care, therapy, and prescriptions due to cost compared to adults not experiencing Long COVID (p<0.0001 for all comparisons).

CONCLUSIONS: These findings may be used to inform healthcare planning for adults experiencing Long COVID and highlight the ongoing need to improve access and affordability of quality and comprehensive care.}, } @article {pmid38761526, year = {2024}, author = {Goldenberg, DL}, title = {How to understand the overlap of long COVID, chronic fatigue syndrome/myalgic encephalomyelitis, fibromyalgia and irritable bowel syndromes.}, journal = {Seminars in arthritis and rheumatism}, volume = {67}, number = {}, pages = {152455}, doi = {10.1016/j.semarthrit.2024.152455}, pmid = {38761526}, issn = {1532-866X}, mesh = {Humans ; *Irritable Bowel Syndrome/physiopathology ; *Fibromyalgia/physiopathology ; *Fatigue Syndrome, Chronic/virology/physiopathology ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Long COVID should be limited to patients with multiple, persistent symptoms not related to well-defined organ damage. Once redefined, a focused review of long COVID demonstrates striking similarity to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), fibromyalgia (FM) and irritable bowel syndrome (IBS). Research in long COVID has revealed similar findings to those noted in CFS/ME and FM, characterized by central nervous system organ dysfunction. Long COVID, like CFS/ME, FM and IBS, is best understood as a bidirectional mind-body, neuroimmune illness.}, } @article {pmid38761171, year = {2024}, author = {Murphy, C and Dalton, P and Boateng, K and Hunter, S and Silberman, P and Trachtman, J and Schrandt, S and Naimi, B and Garvey, E and Joseph, PV and Frank, C and Albertazzi, A and Nyquist, G and Rawson, NE}, title = {Integrating the patient's voice into the research agenda for treatment of chemosensory disorders.}, journal = {Chemical senses}, volume = {49}, number = {}, pages = {}, pmid = {38761171}, issn = {1464-3553}, support = {F32 DC020658/DC/NIDCD NIH HHS/United States ; R01 AG062006/AG/NIA NIH HHS/United States ; R01AG062006-05/NH/NIH HHS/United States ; }, mesh = {Humans ; Middle Aged ; Adult ; *Olfaction Disorders/drug therapy ; Male ; *COVID-19/complications ; Female ; Adolescent ; Young Adult ; SARS-CoV-2/isolation & purification ; Aged ; Surveys and Questionnaires ; Taste Disorders/drug therapy ; Zinc/therapeutic use ; }, abstract = {World-wide some 658 million people were infected with coronavirus disease 2019 (COVID-19) and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients' perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the US Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18 to 24, 25 to 39, 40 to 60, and 60+ yrs. who were treated with nasal steroids, oral steroids, zinc, nasal rinse, smell training, theophylline, platelet-rich plasma, and Omega 3. The most consistent predictor was age, with the majority of those 40 to 60 and 60+ reporting that nasal steroids, oral steroids, zinc, nasal rinse, and smell training were only slightly effective or not effective at all. Many of these treatment strategies target regeneration and immune response, processes compromised by age. Only those under 40 reported more than slight efficacy of steroids or smell training. Findings emphasize the need to include patients of all ages in clinical trials. Older adults with olfactory impairment are at increased risk for Alzheimer's disease (AD). We speculate that olfactory impairment associated with long COVID introduces the potential for a significant rise in AD. Long COVID-associated chemosensory impairment increases the urgency for translational and clinical research on novel treatment strategies. Suggestions for high-priority areas for epidemiological, basic, and clinical research on chemosensory impairment follow.}, } @article {pmid38760030, year = {2024}, author = {Sunkersing, D and Ramasawmy, M and Alwan, NA and Clutterbuck, D and Mu, Y and Horstmanshof, K and Banerjee, A and Heightman, M}, title = {What is current care for people with Long COVID in England? A qualitative interview study.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e080967}, pmid = {38760030}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; England ; Male ; Female ; *Qualitative Research ; Middle Aged ; Aged ; *SARS-CoV-2 ; Adult ; Interviews as Topic ; Health Services Accessibility ; Primary Health Care/organization & administration ; Post-Acute COVID-19 Syndrome ; Health Personnel/psychology ; State Medicine ; }, abstract = {OBJECTIVE: To investigate current care for people with Long COVID in England.

DESIGN: In-depth, semistructured interviews with people living with Long COVID and Long COVID healthcare professionals; data analysed using thematic analysis.

SETTING: National Health Service England post-COVID-19 services in six clinics from November 2022 to July 2023.

PARTICIPANTS: 15 healthcare professionals and 21 people living with Long COVID currently attending or discharged (18 female; 3 male).

RESULTS: Health professionals and people with lived experience highlighted the multifaceted nature of Long COVID, including its varied symptoms, its impact on people's lives and the complexity involved in managing this condition. These impacts encompass physical, social, mental and environmental dimensions. People with Long COVID reported barriers in accessing primary care, as well as negative general practitioner consultations where they felt unheard or invalidated, though some positive interactions were also noted. Peer support or support systems proved highly valuable and beneficial for individuals, aiding their recovery and well-being. Post-COVID-19 services were viewed as spaces where overlooked voices found validation, offering more than medical expertise. Despite initial challenges, healthcare providers' increasing expertise in diagnosing and treating Long COVID has helped refine care approaches for this condition.

CONCLUSION: Long COVID care in England is not uniform across all locations. Effective communication, specialised expertise and comprehensive support systems are crucial. A patient-centred approach considering the unique complexities of Long COVID, including physical, mental health, social and environmental aspects is needed. Sustained access to post-COVID-19 services is imperative, with success dependent on offering continuous rehabilitation beyond rapid recovery, acknowledging the condition's enduring impacts and complexities.}, } @article {pmid38759575, year = {2024}, author = {Torres, F and Shedd, C and Kaza, V and Bollineni, S and Banga, A and Mohanka, MR and Ladikos, N and Wijesinha, M and Mahan, LD and Lawrence, A and Joerns, J and Terada, L and Timofte, I}, title = {Outpatient management of Post-COVID syndrome - single center experience.}, journal = {Heart & lung : the journal of critical care}, volume = {67}, number = {}, pages = {137-143}, doi = {10.1016/j.hrtlng.2024.05.004}, pmid = {38759575}, issn = {1527-3288}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Dyspnea/etiology/diagnosis ; SARS-CoV-2 ; Lung Diseases, Interstitial/drug therapy/complications/physiopathology/diagnosis ; Ambulatory Care/methods ; Tachycardia/etiology ; Post-Acute COVID-19 Syndrome ; Metoprolol/therapeutic use/administration & dosage ; }, abstract = {BACKGROUND: COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management.

OBJECTIVES: To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic.

METHODS: We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment.

RESULTS: In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea.

CONCLUSIONS: Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.}, } @article {pmid38757870, year = {2024}, author = {Kyung, S and Son, Y and Kim, M and Kang, J and Smith, L and Lee, H and Yon, DK}, title = {Risks of alopecia areata in long COVID: Binational population-based cohort studies from South Korea and Japan.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, pages = {e29668}, doi = {10.1002/jmv.29668}, pmid = {38757870}, issn = {1096-9071}, support = {RS-2023-00248157//National Research Foundation of Korea (NRF)/ ; }, mesh = {Humans ; *Alopecia Areata/epidemiology ; *COVID-19/epidemiology/complications ; Republic of Korea/epidemiology ; Male ; Female ; Japan/epidemiology ; Middle Aged ; Adult ; Cohort Studies ; Risk Factors ; Aged ; SARS-CoV-2 ; Young Adult ; Incidence ; }, abstract = {Previous studies have proposed alopecia areata (AA) as a potential outcome of COVID-19 infection among autoimmune diseases, yet the findings might be inconclusive and difficult to generalize due to limited sample sizes and evidence levels. Thus, we aimed to investigate in detail the long-term risk of AA following SARS-CoV-2 infection based on large, binational, general population-based cohort studies. Our study investigated the long-term AA risk after SARS-CoV-2 infection by analyzing bi-national, claim-based cohorts in South Korea and Japan: a Korean nationwide cohort (K-COV-N cohort; discovery cohort; total n = 10 027 506) and a Japanese claims-based cohort (JMDC cohort; validation cohort; total n = 12 218 680). AA was identified based on the international classification of diseases 10th revision code (L63) requiring at least three claims within 1 year. After exposure-driven propensity score matching, SARS-CoV-2 infection was associated with an increased risk of incident AA (aHR, 1.66; 95% CI, 1.38-1.99). This increased risk was observed and persisted for up to 6 months. A similar pattern was observed in the validation cohort. As modifiable factors, severe COVID-19 increased the risk of AA, whereas receiving two or more doses of the COVID-19 vaccine before infection decreased the risk of AA. Through a bi-national cohort study in South Korea and Japan, SARS-CoV-2 infection was associated with an elevated risk for incident AA in the aspect of long COVID.}, } @article {pmid38757616, year = {2024}, author = {Gandhi, RS and Raman, B}, title = {The complexity of cardiovascular long COVID: where we are.}, journal = {Cardiovascular research}, volume = {120}, number = {8}, pages = {e30-e32}, pmid = {38757616}, issn = {1755-3245}, support = {/WT_/Wellcome Trust/United Kingdom ; 302210/Z/23/Z//Wellcome Career Development Award/ ; }, mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/virology/epidemiology/physiopathology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, } @article {pmid38757107, year = {2024}, author = {Emiroglu, C and Dicle, M and Ozagar, SD and Gorpelioglu, S and Aypak, C}, title = {Evaluation of post-acute-COVID-19, and long-COVID symptoms with a questionnaire: Within one year, a longitudinal study.}, journal = {Northern clinics of Istanbul}, volume = {11}, number = {2}, pages = {105-114}, pmid = {38757107}, issn = {2536-4553}, abstract = {OBJECTIVE: Long-term consequences of COVID-19 vary widely, representing a growing global health challenge. The aim of this report was to define the presence of symptoms in post-acute-COVID-19 syndrome (PCS) patients and to assess the frequency, associated factors, and the spectrum of persistent symptoms.

METHODS: In this longitudinal study, 487 adults with a previously diagnosed "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) who admitted to COVID-19 follow-up outpatient clinic between December 1, 2020 and November 31, 2021 were interviewed face-to-face three times. Data was collected on patient demographics, comorbidities, and symptoms. A questionnaire of 160 questions was asked and organized into the following: identification and consent, socio-demographic/epidemiological characteristics, previous medical history, diagnosis and clinical presentation of acute COVID-19, as well as systematic symptoms. Data were evaluated using univariate comparisons and multiple logistic regression.

RESULTS: The most prevalent symptoms among all PCS patients during their initial visit were dyspnea, weakness, forgetfulness, fatigue, and arthralgia respectively. The most common symptoms in patients with 6 months or more time from discharge to follow-up at the first and second visits, appear to be persistent. While incidence rates decreased by the third visit, the five most common symptoms remained the same. The possibility of weakness and arthralgia was found to be higher in non-hospitalized patients. Females were associated with the most common persistent symptoms and the strongest association was with arthralgia.

CONCLUSION: A large number of COVID-19 survivors had continuing symptoms at the first year of post-COVID-19-infection. Neither the presence of comorbidities of the patient nor smoking status were associated with the severity of PCS symptoms. A better understanding of the mechanisms, predisposing factors and evaluation require a multidisciplinary team approach.}, } @article {pmid38756213, year = {2024}, author = {Zheng, ZS and Simonian, N and Wang, J and Rosario, ER}, title = {Transcutaneous vagus nerve stimulation improves Long COVID symptoms in a female cohort: a pilot study.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1393371}, pmid = {38756213}, issn = {1664-2295}, abstract = {BACKGROUND: Long COVID, also known as Post-COVID-19 syndrome, is characterized by multisystemic symptoms that persists for weeks to years beyond acute infection. It disproportionately affects women and those with pre-existing anxiety/depression, conditions more prevalent in females. The vagus nerve, with its extensive innervation and regulation of critical bodily functions, has become a focal point for therapeutic interventions. Transcutaneous vagus nerve stimulation (t-VNS) has emerged as a promising non-invasive treatment for COVID-19 conditions.

METHODS: This pilot study assessed the efficacy of t-VNS in 24 female Long COVID patients (45.8 ± 11.7 years old; 20.2 ± 7.1 months since infection), who underwent a 10-day t-VNS intervention at home (30 min/session, twice a day). Cognition was considered the primary outcome, with anxiety, depression, sleep, fatigue, and smell as secondary outcomes. Outcomes were measured at baseline, post-intervention, and 1-month follow-up.

RESULTS: Significant improvements were observed in various cognitive functions, anxiety, depression, and sleep at post-intervention, with benefits remaining or progressing at 1-month follow-up. Improvements in fatigue were delayed, reaching statistical significance at 1-month follow-up compared to baseline. No significant changes were noted in olfactory performance.

CONCLUSION: This pilot study provides preliminary evidence supporting the potential of t-VNS as a therapeutic intervention for female Long COVID patients. The encouraging results justify further rigorous investigation through larger, randomized controlled trials to confirm the efficacy of t-VNS, assess its generalizability to male cohorts, and explore biological markers to inform personalized treatment approaches. Our findings support the allocation of resources to conduct such trials and advance the understanding of t-VNS as a potential treatment for Long COVID.}, } @article {pmid38755688, year = {2024}, author = {Knopman, DS and Laskowitz, DT and Koltai, DC and Charvet, LE and Becker, JH and Federman, AD and Wisnivesky, J and Mahncke, H and Van Vleet, TM and Bateman, L and Kim, DY and O'Steen, A and James, M and Silverstein, A and Lokhnygina, Y and Rich, J and Feger, BJ and Zimmerman, KO}, title = {RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).}, journal = {Trials}, volume = {25}, number = {1}, pages = {326}, pmid = {38755688}, issn = {1745-6215}, support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; 1OT2HL156812-01 (OTA-20-011)/NH/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; *Cognitive Dysfunction/therapy/psychology/diagnosis ; Prospective Studies ; *SARS-CoV-2 ; *Multicenter Studies as Topic ; *Clinical Trials, Phase II as Topic ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Transcranial Direct Current Stimulation ; Cognition ; Treatment Outcome ; Cognitive Behavioral Therapy/methods ; Quality of Life ; }, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.

METHODS: RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English.

DISCUSSION: This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.}, } @article {pmid38755365, year = {2024}, author = {Berlit, P}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {9}, pages = {24}, doi = {10.1007/s15006-024-3936-x}, pmid = {38755365}, issn = {1613-3560}, mesh = {Humans ; *COVID-19/diagnosis ; *Biomarkers/blood ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38754738, year = {2024}, author = {Erinoso, O and Osibogun, O and Balakrishnan, S and Yang, W}, title = {Long COVID among US adults from a population-based study: Association with vaccination, cigarette smoking, and the modifying effect of chronic obstructive pulmonary disease (COPD).}, journal = {Preventive medicine}, volume = {184}, number = {}, pages = {108004}, pmid = {38754738}, issn = {1096-0260}, support = {K01 DA055127/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/epidemiology ; *COVID-19/prevention & control/epidemiology ; Male ; Female ; Middle Aged ; United States/epidemiology ; *Cigarette Smoking/epidemiology ; Aged ; Adult ; *COVID-19 Vaccines/administration & dosage ; *SARS-CoV-2 ; *Behavioral Risk Factor Surveillance System ; Risk Factors ; Vaccination/statistics & numerical data ; Prevalence ; }, abstract = {OBJECTIVE: Post-COVID Conditions (or Long COVID) have been widely reported, but population-based studies exploring the relationship between its risk factors are lacking. We examined the associations between Long COVID, chronic obstructive pulmonary disease [COPD], vaccination status, and cigarette smoking. We also tested for the modifying effect of COPD status.

METHODS: Data from the 2022 US nationwide Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Our primary outcome was Long COVID (Yes/No) after a positive COVID-19 diagnosis. Predictor variables were COPD, coronary heart disease (CHD), diabetes, asthma, body mass index, cigarette smoking status, and number of COVID-19 vaccinations (0-4). Weighted multivariable logistic regression models were used and adjusted for sociodemographic factors. Regression models were used to explore the modifying effects of COPD status.

RESULTS: The weighted prevalence of Long COVID among survivors (N = 121,379) was 21.8% (95%CI: 21.4, 22.3), with tiredness/fatigue (26.2% [95%:25.1, 27.2]) as the most common symptom. Respondents with COPD (aOR: 1.71 [95%CI: 1.45, 2.02]), current daily smokers (aOR: 1.23 [95%CI:1.01, 1.49]), and former smokers (aOR: 1.24 [95%CI:1.12, 1.38]) (vs. never established smokers) had higher odds of Long COVID. However, respondents who had received three (aOR: 0.75 [95%CI:0.65, 0.85]) and four (aOR: 0.71 [95%CI:0.58, 0.86]) vaccine doses (vs. no vaccine) had lower odds of Long COVID. COPD had a modifying effect on the relationship between cigarette smoking and Long COVID (p-value: 0.013).

CONCLUSION: Our findings underscore a complex interaction between COPD, cigarette smoking, and Long COVID. Further, COVID-19 vaccination may be protective against Long COVID.}, } @article {pmid38753568, year = {2024}, author = {Elizarrarás-Rivas, J and Ramirez-Garcia, SA and Hernández-Osorio, LA and Salas-Alfaro, R and Elizarrarás-Cruz, JD}, title = {Serum levels of anti-Ro52/TRIM21 antibodies in SARS-CoV-2 genetic variants and long COVID. Beyond their application in autoimmune diseases.}, journal = {Gaceta medica de Mexico}, volume = {160}, number = {1}, pages = {112-113}, doi = {10.24875/GMM.M24000851}, pmid = {38753568}, issn = {0016-3813}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Autoimmune Diseases/blood/immunology ; *Ribonucleoproteins/immunology ; Autoantibodies/blood ; }, } @article {pmid38750713, year = {2024}, author = {Sanal-Hayes, NEM and Mclaughlin, M and Hayes, LD and Berry, ECJ and Sculthorpe, NF}, title = {Examining Well-Being and Cognitive Function in People with Long COVID and ME/CFS, and Age-Matched Healthy Controls: A Case-Case-Control Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.041}, pmid = {38750713}, issn = {1555-7162}, abstract = {BACKGROUND: Well-being and cognitive function had not previously been compared between people with long COVID and people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Therefore, this study examined well-being and cognitive function in people with long COVID (∼16 months illness duration; n = 17) and ME/CFS (∼16 years illness duration; n = 24), versus age-matched healthy controls (n = 16).

METHODS: Well-being was examined using several questionnaires, namely the Health Visual Analogue Scale (VAS), Fatigue Severity Scale (FSS), post-exertional malaise (PEM), Pittsburgh Sleep Quality Index (PSQI), European Quality of Life-5 Domains (EQ-5D), MRC Dyspnoea, Self-Efficacy (SELTC), The Edinburgh Neurosymptoms Questionnaire (ENS), General Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9). Cognitive function was examined using Single Digit Modalities Test (SDMT), Stroop test and Trails A and B. These were delivered via a mobile application (app) built specifically for this remote data collection.

RESULTS: The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable on all well-being and cognitive function measures, but self-reported worse values for pain, fatigue, post-exertional malaise, sleep quality, general well-being in relation to mobility, usual activities, self-care, breathlessness, neurological symptoms, self-efficacy and other well-being such as anxiety and depression, compared to controls. There was no effect of group for cognitive function measures.

CONCLUSIONS: These data suggest that both people with long COVID and people with ME/CFS have similar impairment on well-being measures examined herein. Therefore, interventions that target well-being of people with ME/CFS and long COVID are required.}, } @article {pmid38750610, year = {2024}, author = {Gonçalves, D and Costa, JP and Silva, S and Tavares, M and Barros, H and Meireles, P}, title = {The association between probable post-COVID-19 condition and sleep-related parameters: a longitudinal study of non-hospitalised patients.}, journal = {Journal of sleep research}, volume = {33}, number = {6}, pages = {e14215}, pmid = {38750610}, issn = {1365-2869}, support = {613735895//Fundação para a Ciência e a Tecnologia (FCT)/ ; DFA/BD/8562/2020//Fundação para a Ciência e a Tecnologia (FCT)/ ; LA/P/0064/2020//Fundação para a Ciência e a Tecnologia (FCT)/ ; UIDB/04750/2020//Fundação para a Ciência e a Tecnologia (FCT)/ ; }, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Middle Aged ; Longitudinal Studies ; *Sleep Quality ; Adult ; Sleep Wake Disorders/etiology/epidemiology ; Aged ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Portugal/epidemiology ; }, abstract = {The long-term effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on sleep remain poorly known. We evaluated the association between probable post-COVID-19 condition and changes in sleep quality and quantity before and after SARS-CoV-2 infection in a consecutive sample of non-hospitalized adults. Individuals were identified with SARS-CoV-2 infection in 2020 at the central laboratory of a tertiary hospital in Porto and followed as outpatients. We included patients diagnosed with SARS-CoV-2 infection ≥3 months before this evaluation, with no missing data on key variables (n = 2445). Participants completed a questionnaire that included sociodemographic, clinical, and infection-related questions. We computed changes in sleep-related parameters referred to 1 month before diagnosis and 1 week before the questionnaire. Multinomial logistic regression models were fitted to compute crude and adjusted odds ratios and 95% confidence intervals (95% CIs). Compared to the pre-infection period, those with probable post-COVID-19 condition reported a greater decrease in hours of sleep, had a 2.60 (95% CI 2.02-3.34) higher adjusted odds of perceiving their sleep quality as worsened and experienced a significant increase in number of days with sleeping disturbances as defined according to multiple items. The association between post-COVID-19 condition and indicators of poor sleep health requires special attention from healthcare professionals and services. It is essential that appropriate multidisciplinary care is provided to mitigate the physical, psychological, social, and professional impact of sleeping problems in these already burdened patients.}, } @article {pmid38750527, year = {2024}, author = {Lo, PC and Feng, JY and Hsiao, YH and Su, KC and Chou, KT and Chen, YM and Ko, HK and Perng, DW}, title = {Long COVID symptoms after 8-month recovery: persistent static lung hyperinflation associated with small airway dysfunction.}, journal = {Respiratory research}, volume = {25}, number = {1}, pages = {209}, pmid = {38750527}, issn = {1465-993X}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/physiopathology/complications/epidemiology/diagnosis/immunology ; Prospective Studies ; *Post-Acute COVID-19 Syndrome ; *Lung/physiopathology ; *Respiratory Function Tests/methods ; Aged ; Adult ; Recovery of Function ; Time Factors ; Dyspnea/physiopathology/epidemiology/diagnosis ; Forced Expiratory Volume/physiology ; }, abstract = {BACKGROUND: Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue.

METHODS: 64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes.

RESULTS: SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue.

CONCLUSION: SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC.}, } @article {pmid38749696, year = {2024}, author = {Cooper, K and Duncan, E and Hart-Winks, E and Cowie, J and Shim, J and Stage, E and Tooman, T and Alexander, L and Love, A and Morris, JH and Ormerod, J and Preston, J and Swinton, P}, title = {Exploring the perceptions and experiences of community rehabilitation for Long COVID from the perspectives of Scottish general practitioners' and people living with Long COVID: a qualitative study.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e082830}, pmid = {38749696}, issn = {2044-6055}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Qualitative Research ; *COVID-19/rehabilitation/epidemiology ; Scotland ; *General Practitioners/psychology ; Adult ; Aged ; *SARS-CoV-2 ; Quality of Life ; Health Services Accessibility ; Attitude of Health Personnel ; Post-Acute COVID-19 Syndrome ; Community Health Services/organization & administration ; }, abstract = {OBJECTIVES: To explore the experience of accessing Long COVID community rehabilitation from the perspectives of people with Long COVID and general practitioners (GPs).

DESIGN: Qualitative descriptive study employing one-to-one semistructured virtual interviews analysed using the framework method.

SETTING: Four National Health Service Scotland territorial health boards.

PARTICIPANTS: 11 people with Long COVID (1 male, 10 female; aged 40-65 (mean 53) and 13 GPs (5 male, 8 female).

RESULTS: Four key themes were identified: (1) The lived experience of Long COVID, describing the negative impact of Long COVID on participants' health and quality of life; (2) The challenges of an emergent and complex chronic condition, including uncertainties related to diagnosis and management; (3) Systemic challenges for Long COVID service delivery, including lack of clear pathways for access and referral, siloed services, limited resource and a perceived lack of holistic care, and (4) Perceptions and experiences of Long COVID and its management, including rehabilitation. In this theme, a lack of knowledge by GPs and people with Long COVID on the potential role of community rehabilitation for Long COVID was identified. Having prior knowledge of rehabilitation or being a healthcare professional appeared to facilitate access to community rehabilitation. Finally, people with Long COVID who had received rehabilitation had generally found it beneficial.

CONCLUSIONS: There are several patient, GP and service-level barriers to accessing community rehabilitation for Long COVID. There is a need for greater understanding by the public, GPs and other potential referrers of the role of community rehabilitation professionals in the management of Long COVID. There is also a need for community rehabilitation services to be well promoted and accessible to the people with Long COVID for whom they may be appropriate. The findings of this study can be used by those (re)designing community rehabilitation services for people with Long COVID.}, } @article {pmid38749402, year = {2024}, author = {Anastassopoulou, C and Davaris, N and Ferous, S and Siafakas, N and Boufidou, F and Anagnostopoulos, K and Tsakris, A}, title = {The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.}, journal = {Lifestyle genomics}, volume = {17}, number = {1}, pages = {42-56}, doi = {10.1159/000539292}, pmid = {38749402}, issn = {2504-3188}, mesh = {*COVID-19/complications ; Humans ; *SARS-CoV-2 ; *Olfaction Disorders/physiopathology ; Anosmia/physiopathology ; Post-Acute COVID-19 Syndrome ; Olfactory Mucosa/virology/pathology ; Olfactory Receptor Neurons ; }, abstract = {Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.}, } @article {pmid38748355, year = {2024}, author = {Wang, J and Li, Y and Mu, Y and Huang, K and Li, D and Lan, C and Cui, Y and Wang, J}, title = {Missing microbes in infants and children in the COVID-19 pandemic: a study of 1,126 participants in Beijing, China.}, journal = {Science China. Life sciences}, volume = {67}, number = {8}, pages = {1739-1750}, pmid = {38748355}, issn = {1869-1889}, mesh = {Humans ; *COVID-19/epidemiology/microbiology/virology ; Infant ; *Gastrointestinal Microbiome ; Child, Preschool ; Female ; Male ; *RNA, Ribosomal, 16S/genetics ; Child ; *Feces/microbiology/virology ; SARS-CoV-2/isolation & purification/genetics ; Beijing/epidemiology ; Pandemics ; Bacterial Load ; Cohort Studies ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.}, } @article {pmid38747853, year = {2024}, author = {Campos, MDSB and Brito, GMG and Santos, KSDC and Santos, MAA and Martins-Filho, PR and Sousa, ACS}, title = {Chronotropic incompetence is associated with reduced aerobic conditioning and sedentary behavior in patients with post-acute COVID-19 syndrome.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {66}, number = {}, pages = {e32}, pmid = {38747853}, issn = {1678-9946}, mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Sedentary Behavior ; *Post-Acute COVID-19 Syndrome ; *Exercise/physiology ; Adult ; SARS-CoV-2 ; Exercise Tolerance/physiology ; Brazil/epidemiology ; Heart Rate/physiology ; Exercise Test ; Quality of Life ; }, abstract = {Post-acute COVID-19 syndrome, or long COVID, presents with persistent symptoms, including cough, dyspnea, and fatigue, extending beyond one month after SARS-CoV-2 infection. Cardiac complications such as chest pain and arrhythmias have raised concerns, with chronotropic incompetence (CI), an inadequate heart rate increase during exercise, emerging as a significant condition contributing to diminished exercise tolerance and quality of life. This study estimated the prevalence of CI and explored its association with aerobic capacity and physical activity levels in long COVID patients. A cross-sectional study was conducted at a private hospital in Sergipe, Brazil, involving 93 patients over 18 years old with persistent post-COVID-19 symptoms after confirmed SARS-CoV-2 infections. Exclusion criteria included beta-blocker use, inadequate respiratory exchange ratio, and inability to complete cardiopulmonary exercise testing (CPET). Clinical histories, CPET results, and chronotropic index calculation were used to identify CI, with logistic regression analyzing associated factors. Of the participants (mean age 45 years; average duration since COVID-19 diagnosis 120 days), 20.4% were diagnosed with CI. Logistic regression identified a strong association between CI and sedentary behavior (OR 11.80; 95% CI 2.54 to 54.78; p=0.001). Patients with CI showed lower predicted peak heart rates and maximal oxygen uptake. The prevalence of CI among long COVID patients in this study was approximately 20%, associated with decreased aerobic capacity and increased sedentary behavior. These findings highlight the need for timely diagnosis and therapeutic interventions, including cardiopulmonary rehabilitation, to enhance the quality of life in post-COVID patients with CI. The study's cross-sectional design and its specific context have limited causality inference and generalizability, underscoring the importance of further research in diverse settings.}, } @article {pmid38747018, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Ruiz-Ruigómez, M and Arrieta-Ortubay, E and Rodríguez-Rebollo, C and Akasbi-Moltalvo, M and Pardo-Guimerá, V and Ryan-Murua, P and Lumbreras-Bermejo, C and Pellicer-Valero, OJ and Giordano, R and Arendt-Nielsen, L and Franco-Moreno, A}, title = {Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms 2 years after hospitalization: The VIPER study.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, pages = {e29676}, doi = {10.1002/jmv.29676}, pmid = {38747018}, issn = {1096-9071}, support = {//Consejería de Sanidad, Comunidad de Madrid/ ; //Novo Nordisk Fonden/ ; DNRF121//Danish National Research Foundation/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; //Fondo Europeo De Desarrollo Regional-Recursos REACT-UE del Programa Operativo de Madrid 2014-2020/ ; }, mesh = {Humans ; *COVID-19/virology/complications ; Female ; Male ; *RNA, Viral/blood/genetics ; Middle Aged ; *SARS-CoV-2/genetics ; *Survivors ; *Nasopharynx/virology ; Adult ; *Hospitalization ; *Feces/virology ; Aged ; }, abstract = {The SARS-CoV-2 VIrus PERsistence (VIPER) study investigated the presence of long-lasting SARS-CoV-2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID-19 survivors. The presence of SARS-CoV-2 RNA reverse transcription polymerase chain reactions (RT-PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID-19 survivors with post-COVID symptoms and a comparison group of COVID-19 survivors without post-COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self-reported the presence of any post-COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty-seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID-19 survivors with post-COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS-CoV-2 infection without post-COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS-CoV-2 RNA was identified in three nasopharyngeal samples of patients with post-COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS-CoV-2 RNA was not identified in any sample of survivors without post-COVID symptoms. The most prevalent post-COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS-CoV-2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS-CoV-2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post-COVID symptoms. These results do not support the association between SARS-CoV-2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post-COVID symptomatology in the recruited population.}, } @article {pmid38747003, year = {2024}, author = {Qiao, H and Deng, X and Qiu, L and Qu, Y and Chiu, Y and Chen, F and Xia, S and Muenzel, C and Ge, T and Zhang, Z and Song, P and Bonnin, A and Zhao, Z and Yuan, W}, title = {SARS-CoV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, pages = {e29671}, pmid = {38747003}, issn = {1096-9071}, support = {//W. M. Keck Foundation/ ; R01 AG061288/AG/NIA NIH HHS/United States ; R01 NS122060/NS/NINDS NIH HHS/United States ; R21 AI149365/AI/NIAID NIH HHS/United States ; //Infectious Diseases Society of America/ ; R56 AG082361/AG/NIA NIH HHS/United States ; R01 NS110687/NS/NINDS NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; R01 NS126981/NS/NINDS NIH HHS/United States ; }, mesh = {*Blood-Brain Barrier/virology ; Animals ; *Choroid Plexus/virology/pathology ; *COVID-19/virology/pathology/complications/physiopathology ; Mice ; *SARS-CoV-2 ; Tight Junctions/virology ; Disease Models, Animal ; Angiotensin-Converting Enzyme 2/metabolism ; Inflammation/virology ; Humans ; Pericytes/virology/pathology ; }, abstract = {The coronavirus disease of 2019 (COVID-19) pandemic has led to more than 700 million confirmed cases and nearly 7 million deaths. Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains an important question, which is also centered on the mystery of whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to neurological complications both acutely and in long COVID.}, } @article {pmid38746454, year = {2024}, author = {Shankar, V and Wilhelmy, J and Curtis, EJ and Michael, B and Cervantes, L and Mallajosyula, VA and Davis, RW and Snyder, M and Younis, S and Robinson, WH and Shankar, S and Mischel, PS and Bonilla, H and Davis, MM}, title = {Oxidative Stress is a shared characteristic of ME/CFS and Long COVID.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.04.592477}, pmid = {38746454}, issn = {2692-8205}, support = {P01 AI153559/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; }, abstract = {More than 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition, wherein patients of all ages report fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). With no current treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in over 16 healthy controls, 15 ME/CFS, and 15 LC, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, relative to healthy controls, especially in the memory subset. Using a combination of flow cytometry, bulk RNA-seq analysis, mass spectrometry, and systems chemistry analysis, we also observed aberrations in ROS clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase levels, and glutathione peroxidase 4 mediated lipid oxidative damage. Critically, these changes in redox pathways show striking sex-specific trends. While females diagnosed with ME/CFS exhibit higher total ROS and mitochondrial calcium levels, males with an ME/CFS diagnosis have normal ROS levels, but larger changes in lipid oxidative damage. Further analyses show that higher ROS levels correlates with hyperproliferation of T cells in females, consistent with the known role of elevated ROS levels in the initiation of proliferation. This hyperproliferation of T cells can be attenuated by metformin, suggesting this FDA-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Thus, we report that both ME/CFS and LC are mechanistically related and could be diagnosed with quantitative blood cell measurements. We also suggest that effective, patient tailored drugs might be discovered using standard lymphocyte stimulation assays.}, } @article {pmid38746290, year = {2024}, author = {Mandel, H and Yoo, Y and Allen, A and Abedian, S and Verzani, Z and Karlson, E and Kleinman, L and Mudumbi, P and Oliveira, C and Muszynski, J and Gross, R and Carton, T and Kim, C and Taylor, E and Park, H and Divers, J and Kelly, J and Arnold, J and Geary, C and Zang, C and Tantisira, K and Rhee, K and Koropsak, M and Mohandas, S and Vasey, A and Weiner, M and Mosa, A and Haendel, M and Chute, C and Murphy, S and O'Brien, L and Szmuszkovicz, J and Güthe, N and Santana, J and De, A and Bogie, A and Halabi, K and Mohanraj, L and Kinser, P and Packard, S and Tuttle, K and Thorpe, L and Moffitt, R}, title = {Long COVID incidence in adults and children between 2020 and 2023: a real-world data study from the RECOVER Initiative.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38746290}, issn = {2693-5015}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Estimates of post-acute sequelae of SARS-CoV-2 infection (PASC) incidence, also known as Long COVID, have varied across studies and changed over time. We estimated PASC incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). Overall, 7% of children and 8.5%-26.4% of adults developed PASC, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 4% in children and ranged from 4-7% among adults, representing a lower-bound incidence estimation based on two control groups - contemporary COVID-19 negative and historical patients (2019). Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. Our findings indicate that preventing and mitigating Long COVID remains a public health priority. Examining temporal patterns and risk factors of PASC incidence informs our understanding of etiology and can improve prevention and management.}, } @article {pmid38746213, year = {2024}, author = {Stalker, G and Tudas, R and Garg, A and Graham, L and Thurman, AL and Wiblin, RT and Hamzeh, N and Blount, RJ and Villacreses, R and Zabner, J and Comellas, A and Cho, JL and Pezzulo, A}, title = {Long-COVID improves in 50% of patients after a year in a Midwestern cohort.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.30.24306497}, pmid = {38746213}, abstract = {BACKGROUND: Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.

RESEARCH QUESTION: This study aims to better understand the chronology of long-COVID symptoms.

STUDY DESIGN AND METHODS: We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.

RESULTS: Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/-14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.

INTERPRETATION: Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn't affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.}, } @article {pmid38746044, year = {2024}, author = {Chen, XY and Lu, CL and Wang, QY and Pan, XR and Zhang, YY and Wang, JL and Liao, JY and Hu, NC and Wang, CY and Duan, BJ and Liu, XH and Jin, XY and Hunter, J and Liu, JP}, title = {Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: A systematic review of randomized controlled trials.}, journal = {Integrative medicine research}, volume = {13}, number = {2}, pages = {101039}, pmid = {38746044}, issn = {2213-4220}, abstract = {BACKGROUND: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection.

METHODS: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).

RESULTS: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported.

CONCLUSIONS: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings.

STUDY REGISTRATION: The protocol of this review has been registered at PROSPERO: CRD42022384136.}, } @article {pmid38745674, year = {2024}, author = {Dhingra, S and Fu, J and Cloherty, G and Mallon, P and Wasse, H and Moy, J and Landay, A and Kenny, G}, title = {Identification of inflammatory clusters in long-COVID through analysis of plasma biomarker levels.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1385858}, pmid = {38745674}, issn = {1664-3224}, mesh = {Humans ; *Biomarkers/blood ; Male ; Female ; *COVID-19/immunology/blood ; Middle Aged ; *SARS-CoV-2/immunology ; *Inflammation/blood/immunology ; Aged ; Post-Acute COVID-19 Syndrome ; Cluster Analysis ; Adult ; }, abstract = {Mechanisms underlying long COVID remain poorly understood. Patterns of immunological responses in individuals with long COVID may provide insight into clinical phenotypes. Here we aimed to identify these immunological patterns and study the inflammatory processes ongoing in individuals with long COVID. We applied an unsupervised hierarchical clustering approach to analyze plasma levels of 42 biomarkers measured in individuals with long COVID. Logistic regression models were used to explore associations between biomarker clusters, clinical variables, and symptom phenotypes. In 101 individuals, we identified three inflammatory clusters: a limited immune activation cluster, an innate immune activation cluster, and a systemic immune activation cluster. Membership in these inflammatory clusters did not correlate with individual symptoms or symptom phenotypes, but was associated with clinical variables including age, BMI, and vaccination status. Differences in serologic responses between clusters were also observed. Our results indicate that clinical variables of individuals with long COVID are associated with their inflammatory profiles and can provide insight into the ongoing immune responses.}, } @article {pmid38745394, year = {2024}, author = {Brainin, M and Teuschl, Y and Gelpi, E}, title = {"Spanish flu," encephalitis lethargica, and COVID-19: Progress made, lessons learned, and directions for future research.}, journal = {European journal of neurology}, volume = {31}, number = {11}, pages = {e16312}, pmid = {38745394}, issn = {1468-1331}, mesh = {Humans ; *COVID-19/epidemiology ; History, 20th Century ; Parkinson Disease, Postencephalitic/history/therapy/epidemiology ; Influenza, Human/epidemiology/history/prevention & control/therapy ; Pandemics ; }, abstract = {One hundred years ago, an influenza pandemic swept across the globe that coincided with the development of a neurological condition, named "encephalitis lethargica" for the occurrence of its main symptom, the sudden onset of sleepiness that either developed into coma or gradually receded. Between 1917 and 1920, mortality of the flu was >20 million and of encephalitis lethargica approximately 1 million. For lessons to be learned from this pandemic, it makes sense to compare it with the COVID-19 pandemic, which occurred 100 years later. Biomedical progress had enabled testing, vaccinations, and drug therapies accompanied by public health measures such as social distancing, contact tracing, wearing face masks, and frequent hand washing. From todays' perspective, these public health measures are time honored but not sufficiently proven effective, especially when applied in the context of a vaccination strategy. Also, the protective effects of lockdowns of schools, universities, and other institutions and the restrictions on travel and personal visits to hospitals or old-age homes are not precisely known. Preparedness is still a demand for a future pandemic. Clinical trials should determine the comparative effectiveness of such public health measures, especially for their use as a combination strategy with vaccination and individual testing of asymptomatic individuals. It is important for neurologists to realize that during a pandemic the treatment possibilities for acute stroke and other neurological emergencies are reduced, which has previously led to an increase of mortality and suffering. To increase preparedness for a future pandemic, neurologists play an important role, as the case load of acute and chronic neurological patients will be higher as well as the needs for rehabilitation. Finally, new chronic forms of postviral disease will likely be added, as was the case for postencephalitic parkinsonism a century ago and now has occurred as long COVID.}, } @article {pmid38745298, year = {2024}, author = {Nasrullah, A and Virk, S and Javed, A and Shah, A and Ramanujam, D and Sharma, A and Gutierrez, L and Nauer, K and Maggio, M and Yin, Y and Bajwa, Y and Cheema, T and Disilvio, B}, title = {Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {231}, pmid = {38745298}, issn = {1471-2466}, mesh = {Humans ; *COVID-19/rehabilitation/psychology/complications ; Male ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Quality of Life ; Aged ; *SARS-CoV-2 ; Walk Test ; Dyspnea/etiology/rehabilitation/psychology/physiopathology ; Retrospective Studies ; }, abstract = {BACKGROUND: COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR's effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals.

METHODS: We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network's electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR.

RESULTS: The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR.

CONCLUSION: Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients' functional status should be investigated in the future.}, } @article {pmid38744274, year = {2024}, author = {Hu, WT and Kaluzova, M and Dawson, A and Sotelo, V and Papas, J and Lemenze, A and Shu, C and Jomartin, M and Nayyar, A and Hussain, S}, title = {Clinical and CSF single-cell profiling of post-COVID-19 cognitive impairment.}, journal = {Cell reports. Medicine}, volume = {5}, number = {5}, pages = {101561}, pmid = {38744274}, issn = {2666-3791}, mesh = {Humans ; *COVID-19/cerebrospinal fluid/pathology/complications ; Male ; *Single-Cell Analysis/methods ; Female ; *Cognitive Dysfunction/cerebrospinal fluid/pathology/virology/genetics ; Middle Aged ; *SARS-CoV-2/isolation & purification ; Aged ; Receptors, Immunologic/genetics ; Prospective Studies ; Adult ; Magnetic Resonance Imaging ; Membrane Glycoproteins ; Interleukin-8 ; }, abstract = {Natural history and mechanisms for persistent cognitive symptoms ("brain fog") following acute and often mild COVID-19 are unknown. In a large prospective cohort of people who underwent testing a median of 9 months after acute COVID-19 in the New York City/New Jersey area, we found that cognitive dysfunction is common; is not influenced by mood, fatigue, or sleepiness; and is correlated with MRI changes in very few people. In a subgroup that underwent cerebrospinal fluid analysis, there are no changes related to Alzheimer's disease or neurodegeneration. Single-cell gene expression analysis in the cerebrospinal fluid shows findings consistent with monocyte recruitment, chemokine signaling, cellular stress, and suppressed interferon response-especially in myeloid cells. Longitudinal analysis shows slow recovery accompanied by key alterations in inflammatory genes and increased protein levels of CXCL8, CCL3L1, and sTREM2. These findings suggest that the prognosis for brain fog following COVID-19 correlates with myeloid-related chemokine and interferon-responsive genes.}, } @article {pmid38741940, year = {2024}, author = {Finsterer, J}, title = {Letter to the Editor From J. Finsterer: "Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis".}, journal = {Journal of the Endocrine Society}, volume = {8}, number = {6}, pages = {bvae086}, pmid = {38741940}, issn = {2472-1972}, } @article {pmid38740499, year = {2024}, author = {Naik, H and Cooke, E and Boulter, T and Dyer, R and Bone, JN and Tsai, M and Cristobal, J and McKay, RJ and Song, X and Nacul, L}, title = {Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e085272}, pmid = {38740499}, issn = {2044-6055}, mesh = {Humans ; Double-Blind Method ; *Naltrexone/administration & dosage/therapeutic use ; British Columbia ; *Narcotic Antagonists/administration & dosage/therapeutic use ; COVID-19/complications ; Fatigue Syndrome, Chronic/drug therapy ; Prospective Studies ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; Male ; Clinical Trials, Phase II as Topic ; Female ; }, abstract = {INTRODUCTION: A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required.

METHODS AND ANALYSIS: A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire.

ETHICS AND DISSEMINATION: The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences.

TRIAL REGISTRATION NUMBER: NCT05430152.}, } @article {pmid38739455, year = {2024}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Photobiomodulation in the Treatment of Dysgeusia in Patients with Long COVID: Comment.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {}, number = {}, pages = {}, doi = {10.1089/photob.2024.0040}, pmid = {38739455}, issn = {2578-5478}, } @article {pmid38739435, year = {2024}, author = {Müllenmeister, C and Stoelting, A and Schröder, D and Schmachtenberg, T and Ritter, S and El-Sayed, I and Steffens, S and Klawonn, F and Klawitter, S and Homann, S and Mikuteit, M and Berg, C and Behrens, G and Hummers, E and Cook, A and Müller, F and Dopfer-Jablonka, A and Happle, C}, title = {Evaluating the Feasibility, Acceptance, and Beneficial Effects of Online Occupational Therapy for Post-COVID-19 Condition: Protocol for a Randomized Controlled Trial (ErgoLoCo Study).}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e50230}, pmid = {38739435}, issn = {1929-0748}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/psychology ; *Feasibility Studies ; Germany ; *Occupational Therapy/methods ; Pilot Projects ; SARS-CoV-2 ; Telemedicine ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID.

OBJECTIVE: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation.

METHODS: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints.

RESULTS: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024.

CONCLUSIONS: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS.

TRIAL REGISTRATION: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990.

PRR1-10.2196/50230.}, } @article {pmid38739263, year = {2024}, author = {Ruzicka, M and Sachenbacher, S and Heimkes, F and Uebleis, AO and Karch, S and Grosse-Wentrup, F and Ibarra Fonseca, GJ and Wunderlich, N and Bogner, J and Mayerle, J and von Bergwelt-Baildon, M and Falkai, P and Subklewe, M and Ruzicka, T and Benesch, C and Valdinoci, E and Pernpruner, A and Thomas, A and Heindl, B and Stubbe, HC and Adorjan, K}, title = {Characterization of cognitive symptoms in post COVID-19 patients.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1923-1934}, pmid = {38739263}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/complications ; Male ; Female ; Middle Aged ; *Neuropsychological Tests ; Adult ; *Cognitive Dysfunction/etiology/physiopathology ; Aged ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; Neuroimaging ; }, abstract = {Cognitive symptoms (CS) belong to the most common manifestations of the Post COVID-19 (PC) condition. We sought to objectify CS in PC patients using routine diagnostic assessments: neurocognitive testing (NCT) and brain imaging (BI). Further, we investigated possible associations of CS with patient reported outcomes (PROs), and risk factors for developing CS. Clinical data and PROs of 315 PC patients were assessed at a mean of 6 months after SARS-CoV-2 infection. 231 (73.3%) patients reported any sort of CS. Among them, 78 underwent NCT and 55 received BI. In NCT, the cognitive domains most affected were the working memory, attention, and concentration. Nonetheless, pathological thresholds were exceeded only in few cases. Neurocognitive performance did not differ significantly between patients complaining of severe (n = 26) versus non-severe (n = 52) CS. BI findings were abnormal in 8 (14.5%) cases with CS but were most likely not related to PC. Patients reporting high severity of CS scored worse in the PHQ-9, FSS, WHOQOL-BREF, were more likely to report impaired sleep, and had a higher prevalence of psychiatric diagnoses. Overall, NCT could confirm mild impairment in some but not all PC patients with CS, while BI studies were abnormal in only few cases. CS severity did not affect NCT results, but severe CS were associated with symptoms of depression (PHQ-9), fatigue (FSS), reduced quality of life (WHOQOL-BREF) and higher prevalence of psychiatric illnesses. These findings support the importance of NCT, BI, and neuro-psychological assessment in the work-up of PC patients reporting CS. TRIAL REGISTRATION: Trial registration number and date of registration: DRKS00030974, 22 Dec 2022, retrospectively registered.}, } @article {pmid38738103, year = {2024}, author = {Irie, Y and Wakabayashi, H and Matuzawa, Y and Hiruta, N and Kaneko, K}, title = {A Case of Anti-Synthetase Syndrome With Anti-Glycyl tRNA Synthetases Antibody Developed After COVID-19.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e58004}, pmid = {38738103}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory disease characterized by severe acute infection. In some cases, COVID-19 symptoms may persist for a long term, posing a significant social problem. Long-term COVID-19 symptoms resemble those observed in various autoimmune diseases, such as dermatomyositis and polymyositis. In this report, we present the case of a 55-year-old woman who had been experiencing persistent dyspnea on exertion since contracting COVID-19 a month ago and was subsequently diagnosed with anti-synthetase syndrome (ASS). The patient presented with fever, dyspnea, rash, mechanic's hands, and arthritis. Computed tomography imaging revealed findings indicative of interstitial pneumonia. Immunological test results were positive for anti-EJ antibody, leading to a diagnosis of ASS based on Solomon's established criteria. The patient's condition improved following treatment with prednisolone, tacrolimus, and intravenous cyclophosphamide. Pathological findings of transbronchial biopsy revealed nonspecific interstitial pneumonia with organizing pneumonia, leading to speculation that ASS had developed after COVID-19. Given the scarcity of reports on ASS development post COVID-19, we conducted a literature review and compared our present case to previous ones. This report highlights the importance of considering ASS in the differential diagnosis of patients with long-term COVID-19 symptoms.}, } @article {pmid38737442, year = {2024}, author = {Zhao, X and Wang, D and Chen, Y and Zhang, N and Li, T and Fan, R and Yang, L and Yang, C and Yang, J}, title = {Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study.}, journal = {Open medicine (Warsaw, Poland)}, volume = {19}, number = {1}, pages = {20240950}, pmid = {38737442}, issn = {2391-5463}, abstract = {BACKGROUND: COVID-19 sequelae are long-term symptoms of COVID-19. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection.

OBJECTIVES: The aim of this study is to investigate the cardiovascular system-related symptoms of outpatients and inpatients of the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine after recovery from novel coronavirus infection, analyze the influencing factors, and symptom characteristics of related symptoms, and thereby provide a basis for further formulating a reasonable diagnosis and treatment plan.

MATERIALS AND METHODS: From January 15, 2023 to February 15, 2023, 452 recovered patients with novel coronavirus infection who were admitted to the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine due to symptoms of the cardiovascular system (complaints of chest pain and palpitations) were involved in this study. A unified questionnaire was used to record the general information, past medical history, characteristics of chest pain or palpitations, and other COVID-19-related sequelae of the selected patients. All data were statistically analyzed by SPSS 26.0 statistical software.

RESULTS: A total of 226 patients with cardiovascular symptoms and 226 patients without cardiovascular symptoms were included in this study. After univariate and multivariate logistic regression analysis, women (OR 2.081, 95% CI = 1.358-3.189) and young people (OR 2.557, 95% CI = 1.44-4.54) had a higher risk of cardiovascular symptoms; prehypertension (OR 1.905, 95% CI = 1.091-3.329) and hypertension (OR 2.287, 95% CI = 1.433-3.649) increased the risk of cardiovascular symptoms; patients with history of previous cardiovascular disease (OR 1.862, 95% CI = 1.16-2.988) and history of diabetes (OR 2.138, 95% CI = 1.058-4.319) had a higher risk of developing cardiovascular symptoms. The main symptoms related to COVID-19 sequelae reported by all 452 patients were fatigue (76.8%), shortness of breath (54.2%), dry mouth and bitter mouth (46.0%), gastrointestinal symptoms (42.7%), sleep disturbances (37.4%), sweating (31.9%), chills (29%), dizziness (25.7%), confusion of brain fog (25.2%), and tinnitus (14.6%). Compared with patients without cardiovascular symptoms, patients with cardiovascular symptoms were more likely to have shortness of breath (OR 3.521, 95% CI = 2.226-5.472), gastrointestinal symptoms (OR 2.039, 95% CI = 1.226-3.393), and dry mouth and bitter mouth (OR 1.918, 95% CI = 1.229-2.992). The differences were statistically significant (P < 0.05).

CONCLUSION: In this new coronavirus infection, women, young people, the elderly, people with prehypertension, hypertension, and patients with a history of cardiovascular disease and diabetes have a higher risk of developing cardiovascular symptoms, and patients with cardiovascular symptoms are more likely to develop other COVID-19 sequelae.}, } @article {pmid38737315, year = {2024}, author = {Wodecka, L and Koulouglioti, C and Gonçalves, AC and Hill, A and Hodgson, L}, title = {Exploring the recovery journey of COVID-19 critical care survivors during the first year after hospital discharge.}, journal = {Journal of the Intensive Care Society}, volume = {25}, number = {2}, pages = {181-189}, pmid = {38737315}, issn = {1751-1437}, abstract = {OBJECTIVES: To explore the longitudinal recovery of patients admitted to critical care following COVID-19 over the year following hospital discharge. To understand the important aspects of the patients' recovery process and key elements of their caregivers' experiences during this time.

DESIGN: A longitudinal qualitative study using semi-structured interviews.

SETTING: Two acute hospitals in South East England and follow-up in the community.

PARTICIPANTS: Six COVID-19 critical care survivors from the first wave of the pandemic (March-May 2020) and five relatives were interviewed 3 months after hospital discharge. The same six survivors and one relative were interviewed again at 1 year. Interviews were transcribed verbatim, anonymised and a reflexive thematic analysis was conducted.

RESULTS: Three themes were developed: (1) 'The cycle of guilt, fear and stigma'; (2) 'Facing the uncertainties of recovery' and (3) 'Coping with lingering symptoms - the new norm'. The first theme highlights survivors' reluctance to share their experiences associated with contracting the disease. The second theme, explores challenges faced by the survivors and their relatives in navigating the recovery process, given the unknown nature of the illness. The final theme illustrates the mechanisms survivors develop to come to terms with the remnants of their illness and critical care stay.

CONCLUSIONS: The longitudinal nature of the study highlighted the persisting symptoms of long COVID-19, their impact on survivors and coping methods amidst the ongoing pandemic. Further research into the experiences of those affected in the first and subsequent waves of the COVID-19 pandemic, is desirable to help guide the formulation of the optimally supported recovery pathways.}, } @article {pmid38736712, year = {2024}, author = {Møller, M and Abelsen, T and Sørensen, AIV and Andersson, M and Hansen, LF and Dilling-Hansen, C and Kirkby, N and Vedsted, P and Mølbak, K and Koch, A}, title = {Exploring the dynamics of COVID-19 in a Greenlandic cohort: Mild acute illness and moderate risk of long COVID.}, journal = {IJID regions}, volume = {11}, number = {}, pages = {100366}, pmid = {38736712}, issn = {2772-7076}, abstract = {OBJECTIVES: This study aimed to explore how the Greenlandic population experienced the course of both acute and long-term COVID-19. It was motivated by the unique epidemiologic situation in Greenland, with delayed community transmission of SARS-CoV-2 relative to the rest of the world.

METHODS: In a survey among 310 Greenlandic adults, we assessed the association between previous SARS-CoV-2 infection and overall health outcomes by administering three repeated questionnaires over 12 months after infection, with a response rate of 41% at the 12-month follow-up. The study included 128 individuals with confirmed SARS-CoV-2 infection from January/February 2022 and 182 test-negative controls. Participants were recruited through personal approaches, phone calls, and social media platforms.

RESULTS: A total of 53.7% of 162 participants who were test-positive recovered within 4 weeks and 2.5% were hospitalized due to SARS-CoV-2. The most common symptoms were fatigue and signs of mild upper respiratory tract infection. Less than 5% reported sick leave above 2 weeks after infection. Compared with participants who were test-negative, there was an increased risk of reporting fatigue (risk differences 25.4%, 95% confidence interval 8.8-44.0) and mental exhaustion (risk differences 23.4%, 95% confidence interval 4.8-42.2) up to 12 months after a positive test.

CONCLUSIONS: Our results indicate that during a period dominated by the Omicron variant, Greenlanders experienced a mild acute course of COVID-19, with quick recovery, minimizing the impact on sick leave. Long COVID may be present in Greenlanders, with symptoms persisting up to 12 months after infection. However, it is important to consider the small sample size and modest response rate as limitations when interpreting the results.}, } @article {pmid38735864, year = {2024}, author = {Burton-Fisher, W and Gordon, K}, title = {Holding the hope? Therapist and client perspectives on long COVID recovery: A Q-methodology.}, journal = {British journal of health psychology}, volume = {29}, number = {3}, pages = {746-770}, doi = {10.1111/bjhp.12724}, pmid = {38735864}, issn = {2044-8287}, mesh = {Humans ; *COVID-19/psychology ; Female ; Male ; *Hope ; Adult ; Middle Aged ; United Kingdom ; Psychotherapy/methods ; SARS-CoV-2 ; Aged ; Attitude of Health Personnel ; }, abstract = {PURPOSE: Long COVID is a global health concern which has debilitating effects on the individual experiencing it. In the United Kingdom, psychological therapies are being offered to people with long COVID, although the evidence for these therapies is yet to be demonstrated. This research aimed to understand how therapists and clients define and understand recovery from long COVID, and use hope theory to interpret the results.

METHODS: An online Q-methodology was employed, where participants sorted a range of statements pertaining to long COVID recovery based on their level of agreement with them. These arranged statements (Q-sorts) were collated and factor analysed to explore and compare underlying perspectives.

RESULTS: Sixteen participants were recruited for the study, including eleven clients, four IAPT therapists and one therapist working in the broader long COVID pathway. A four-factor model is reported, including (1) Psychological Pathways to Recovery, (2) Social Context and Agency, (3) Physiological Goals of Recovery and (4) Personal Meaning Making. All IAPT therapists loaded onto the psychological pathways factor, whereas the remaining participants shared more diverse perspectives.

CONCLUSIONS: The belief that long COVID recovery was possible, taken as an indicator of hopefulness, was rated highest for Factor 1, Psychological Pathways to Recovery, and Factor 3, Physiological Recovery Goals. This suggested that having a clear definition of recovery, or clear guidance on how to intervene, promoted hopefulness and, theoretically, well-being. However, clients reported experiences of being invalidated and disbelieved by health professionals, with psychological explanations sometimes being experienced as dismissive and invalidating. Clinical implications and future research directions are discussed.}, } @article {pmid38735404, year = {2024}, author = {Foret-Bruno, P and Shafran, R and Stephenson, T and Nugawela, MD and Chan, D and Ladhani, S and McOwat, K and Mensah, A and Simmons, R and Fox Smith, L and D'oelsnitz, A and Xu, L and Dalrymple, E and Heyman, I and Ford, T and Segal, T and Chalder, T and Rojas, N and Pinto Pereira, SM and , }, title = {Prevalence and co-occurrence of cognitive impairment in children and young people up to 12-months post infection with SARS-CoV-2 (Omicron variant).}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {989-994}, doi = {10.1016/j.bbi.2024.05.001}, pmid = {38735404}, issn = {1090-2139}, mesh = {Humans ; *COVID-19/epidemiology/psychology/complications ; *Cognitive Dysfunction/epidemiology ; Male ; Female ; Adolescent ; Child ; Prevalence ; *SARS-CoV-2 ; Sleep Wake Disorders/epidemiology ; Young Adult ; Mental Fatigue/epidemiology ; Mental Health ; Child, Preschool ; }, abstract = {BACKGROUND: Cognitive impairment is often reported after SARS-CoV-2 infection, yet evidence gaps remain. We aimed to (i) report the prevalence and characteristics of children and young people (CYP) reporting "brain fog" (i.e., cognitive impairment) 12-months post PCR-proven SARS-CoV-2 infection and determine whether differences by infection status exist and (ii) explore the prevalence of CYP experiencing cognitive impairment over a 12-month period post-infection and investigate the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and sleep problems.

METHODS: The Omicron CLoCk sub-study, set up in January 2022, collected data on first-time PCR-test-positive and PCR-proven reinfected CYP at time of testing and at 3-, 6- and 12-months post-testing. We describe the prevalence of cognitive impairment at 12-months, indicating when it was first reported. We characterise CYP experiencing cognitive impairment and use chi-squared tests to determine whether cognitive impairment prevalence varied by infection status. We explore the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and trouble sleeping using validated scales. We examine associations at 3-, 6- and 12-months post-testing by infection status using Mann-Whitney U and chi-square tests.

RESULTS: At 12-months post-testing, 7.0 % (24/345) of first-positives and 7.5 % (27/360) of reinfected CYP experienced cognitive impairment with no difference between infection-status groups (p = 0.78). The majority of these CYP experienced cognitive impairment for the first time at either time of testing or 3-months post-test (no difference between the infection-status groups; p = 0.60). 70.8 % of first-positives experiencing cognitive impairment at 12-months, were 15-to-17-years-old as were 33.3 % of reinfected CYP experiencing cognitive impairment (p < 0.01). Consistently at all time points post-testing, CYP experiencing cognitive impairment were more likely to score higher on all Strengths and Difficulties Questionnaire subscales, higher on the Chalder Fatigue sub-scale for mental fatigue, lower on the Short Warwick-Edinburgh Mental Wellbeing Scale and report more trouble sleeping.

CONCLUSIONS: CYP have a fluctuating experience of cognitive impairment by 12-months post SARS-CoV-2-infection. Cognitive impairment is consistently correlated with poorer sleep, behavioural and emotional functioning over a 12-month period. Clinicians should be aware of cognitive impairment post-infection and its co-occurring nature with poorer sleep, behavioural and mental health symptoms.}, } @article {pmid38735354, year = {2024}, author = {Krumholz, HM and Sawano, M and Bhattacharjee, B and Caraballo, C and Khera, R and Li, SX and Herrin, J and Coppi, A and Holub, J and Henriquez, Y and Johnson, MA and Goddard, TB and Rocco, E and Hummel, AC and Al Mouslmani, M and Putrino, DF and Carr, KD and Carvajal-Gonzalez, S and Charnas, L and De Jesus, M and Ziegler, FW and Iwasaki, A}, title = {The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-Blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.030}, pmid = {38735354}, issn = {1555-7162}, abstract = {BACKGROUND: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID.

METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders.

CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.}, } @article {pmid38735020, year = {2024}, author = {Yang, C and Tan, Y and Li, Z and Hu, L and Chen, Y and Zhu, S and Hu, J and Huai, T and Li, M and Zhang, G and Rao, D and Fei, G and Shao, M and Ding, Z}, title = {Pulmonary redox imbalance drives early fibroproliferative response in moderate/severe coronavirus disease-19 acute respiratory distress syndrome and impacts long-term lung abnormalities.}, journal = {Annals of intensive care}, volume = {14}, number = {1}, pages = {72}, pmid = {38735020}, issn = {2110-5820}, support = {KJ2021A0306//Anhui Provincial Department of Education/ ; }, abstract = {BACKGROUND: COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities.

METHODS: Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge.

RESULTS: Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p < 0.001) and NT-PCP-III (p < 0.001), TGF-β1 (p < 0.001), GSSG (p < 0.001), and MDA (p < 0.001) concentrations on admission, while decreased SOD (p < 0.001) and GSH (p < 0.001) levels were observed in BALF. Both NT-PCP-III and TGF-β1 in BALF from COVID-19 ARDS group were directly correlated with GSSG (p < 0.001) and MDA (p < 0.001) and were inversely correlated with SOD (p < 0.001) and GSH (p < 0.001). Within COVID-19 ARDS group, non-survivors (n = 28) showed significant pulmonary fibroproliferation (p < 0.001) with more severe redox imbalance (p < 0.001) than survivors (n = 37). Furthermore, according to data from COVID-19 ARDS survivor follow-up (n = 37), radiographic residual pulmonary fibrosis and lung function impairment improved 3 months after discharge compared with discharge (p < 0.001) and were associated with early pulmonary fibroproliferation and redox imbalance (p < 0.01).

CONCLUSIONS: Pulmonary redox imbalance occurring early in COVID-19 ARDS patients drives fibroproliferative response and increases the risk of death. Long-term lung abnormalities post-COVID-19 are associated with early pulmonary fibroproliferation and redox imbalance.}, } @article {pmid38732609, year = {2024}, author = {Atieh, O and Durieux, JC and Baissary, J and Mouchati, C and Labbato, D and Thomas, A and Merheb, A and Ailstock, K and Funderburg, N and McComsey, GA}, title = {The Long-Term Effect of COVID-19 Infection on Body Composition.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732609}, issn = {2072-6643}, support = {UM1TR004528//Clinical and Translational Science Collaborative of Northern Ohio/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Female ; Male ; *Body Composition ; Adult ; Prospective Studies ; *Absorptiometry, Photon ; Middle Aged ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: The effect of COVID-19 infection versus the indirect effect of the pandemic on body composition remains unclear. This study investigates the long-term changes in body composition in COVID-19 survivors compared to a contemporary control group.

METHOD: This is a prospective study involving adults who underwent a pre-pandemic whole-body DXA scan (DXA#1) between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including their medical and COVID-19 history. Inflammation markers and fasting lipids were measured. For those participants who experienced a COVID-19 infection between the two DXAs, DXA#2 was acquired at least one year after COVID-19 infection.

RESULTS: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n = 80) of the participants experienced a COVID-19 infection between their two DXA scans (COVID-19+ group), and the other half had never had COVID-19. COVID-19-negative participants displayed an increase in annualized trunk fat (g) [922.5 vs. 159.7; p = 0.01], total fat (g) [1564.3 vs. 199.9; p = 0.2], and LBM (g) [974.9 vs. -64.5; p = 0.0002] when compared to the COVID-19+ group. However, among the COVID-19+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p > 0.05).

CONCLUSION: During the pandemic, both the COVID-19 survivors and the COVID-19-negative group exhibited increases in weight, total fat, and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19 survivors displayed a decline in lean body mass over the same period, regardless of PASC symptoms.}, } @article {pmid38732592, year = {2024}, author = {Sinopoli, A and Sciurti, A and Isonne, C and Santoro, MM and Baccolini, V}, title = {The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732592}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements ; *COVID-19/prevention & control/mortality ; *Vitamins/therapeutic use ; *Vitamin D/therapeutic use/administration & dosage ; *Randomized Controlled Trials as Topic ; *Ascorbic Acid/therapeutic use/administration & dosage ; *SARS-CoV-2 ; *Vitamin A/therapeutic use/administration & dosage ; COVID-19 Drug Treatment ; Vitamin B Complex/therapeutic use ; }, abstract = {This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.}, } @article {pmid38732160, year = {2024}, author = {Riou, M and Coste, F and Meyer, A and Enache, I and Talha, S and Charloux, A and Reboul, C and Geny, B}, title = {Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {9}, pages = {}, pmid = {38732160}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications/virology/pathology ; *SARS-CoV-2/pathogenicity ; Lung/blood supply/pathology/virology ; Pulmonary Embolism/virology/etiology ; Hypertension, Pulmonary/etiology/physiopathology/virology/pathology ; Post-Acute COVID-19 Syndrome ; Thrombosis/virology/etiology/pathology ; }, abstract = {Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.}, } @article {pmid38730998, year = {2024}, author = {Moustafa, IM and Ahbouch, A and Kader, RP and Shousha, TM and Alrahoomi, A}, title = {A Comparison of Sensorimotor Integration and Motor Fitness Components between Collegiate Athletes with and without Long COVID: A Cross-Sectional Study with Pair-Matched Controls.}, journal = {Journal of clinical medicine}, volume = {13}, number = {9}, pages = {}, pmid = {38730998}, issn = {2077-0383}, support = {2201050573//University of Sharjah/ ; }, abstract = {Background: Long COVID presents a concern for collegiate athletes, potentially impacting sensorimotor processing and motor fitness. This study aimed to assess these effects. Methods: This cross-sectional study involved 60 athletes diagnosed with Long COVID and 60 controls. Sensorimotor processing and integration were evaluated using neurophysiological variables (N13, P14, N20, P27, and N30), while motor fitness was assessed through balance, agility, and vertical jump testing. T-tests compared groups, and Pearson's correlations explored relationships. Results: Significant differences (p < 0.001) were observed in neurophysiological variables and motor fitness between Long COVID and control groups. Fatigue correlated positively (p < 0.001) with neurophysiological variables in Long COVID cases but not with motor fitness (p = 0.08, p = 0.07, p = 0.09). Conclusions: Collegiate athletes with Long COVID exhibit abnormal sensorimotor processing, integration, and diminished motor fitness compared to uninfected peers. The fatigue severity of Long COVID correlates with neurophysiological changes, suggesting a link between sensorimotor deficits and fatigue. Targeted interventions for sensorimotor deficits and fatigue management are crucial for athletes recovering from Long COVID. This study underscores the importance of addressing these issues to optimize the recovery and performance of collegiate athletes affected by Long COVID.}, } @article {pmid38729647, year = {2024}, author = {O'Connor, RJ and Parkin, A and Mir, G and Mullard, J and Baley, S and Ceolta-Smith, J and Rayner, C}, title = {Work and vocational rehabilitation for people living with long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {385}, number = {}, pages = {e076508}, doi = {10.1136/bmj-2023-076508}, pmid = {38729647}, issn = {1756-1833}, mesh = {Humans ; *COVID-19/rehabilitation ; *Rehabilitation, Vocational/methods ; *SARS-CoV-2 ; Return to Work ; Pandemics ; }, } @article {pmid38729195, year = {2024}, author = {Knuppel, A and Boyd, A and Macleod, J and Chaturvedi, N and Williams, DM}, title = {The long COVID evidence gap in England.}, journal = {Lancet (London, England)}, volume = {403}, number = {10440}, pages = {1981-1982}, doi = {10.1016/S0140-6736(24)00744-X}, pmid = {38729195}, issn = {1474-547X}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; England/epidemiology ; Evidence Gaps ; Evidence-Based Medicine ; *Post-Acute COVID-19 Syndrome/epidemiology ; }, } @article {pmid38728912, year = {2024}, author = {Argento, F and Donato, M and Villalba, D and Sarubbio, MG and Giménez, A and Ciapponi, A and Augustovski, F}, title = {Mortalidad, Secuelas Clínicas y Calidad de Vida Luego del Alta de Unidades de Cuidados Intensivos en Pacientes con COVID-19: Estudio Multicéntrico Descriptivo en Argentina.}, journal = {Value in health regional issues}, volume = {42}, number = {}, pages = {100989}, doi = {10.1016/j.vhri.2024.100989}, pmid = {38728912}, issn = {2212-1102}, mesh = {Humans ; *COVID-19/mortality/psychology/epidemiology ; Argentina/epidemiology ; Male ; *Quality of Life/psychology ; Female ; *Intensive Care Units ; Cross-Sectional Studies ; *Patient Discharge/statistics & numerical data ; Middle Aged ; Aged ; SARS-CoV-2 ; Patient Readmission/statistics & numerical data ; Adult ; Critical Illness ; }, abstract = {OBJECTIVE: Patients with COVID-19 who require hospitalization in an intensive care unit, in addition to being at risk of presenting premature death, have higher rates of complications. This study aimed to describe mortality, rehospitalizations, quality of life, and symptoms related to postintensive care syndrome (PICS) and prolonged COVID-19 in patients with COVID-19 discharged from the intensive care unit in hospitals in Argentina.

METHODS: A cross-sectional study was conducted in 4 centers in the Autonomous City and province of Buenos Aires as of December 2022. The variables of interest were mortality after discharge, rehospitalization, health-related quality of life, post-COVID-19-related symptoms, cognitive status, and PICS. Data collection was by telephone interview between 6 and 18 months after discharge.

RESULTS: A total of 124 patients/families were contacted. Mortality was 7.3% (95% CI: 3.87-13.22) at 14.46 months of follow-up after discharge. Patients reported a reduction of the EQ-5D-3L visual analog scale of 13.8 points, reaching a mean of 78.05 (95% CI: 73.7-82.4) at the time of the interview. Notably, 54.4% of patients (95% CI: 41.5-66.6) reported cognitive impairment and 66.7% (95% CI: 53.7-77.5) developed PICS, whereas 37.5% (95% CI: 26-50.9) had no symptoms of prolonged COVID-19.

CONCLUSION: The results showed a significant impact on the outcomes studied, consistent with international evidence.}, } @article {pmid38727085, year = {2024}, author = {Wu, JY and Chen, CC and Liu, MY and Hsu, WH and Tsai, YW and Liu, TH and Pin-Chien, S and Huang, PY and Chuang, MH and Lee, MC and Hung, KC and Yu, T and Lai, CC}, title = {Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.}, journal = {Journal of medical virology}, volume = {96}, number = {5}, pages = {e29662}, doi = {10.1002/jmv.29662}, pmid = {38727085}, issn = {1096-9071}, mesh = {Humans ; *Ritonavir/therapeutic use ; Male ; Female ; Child ; Retrospective Studies ; *COVID-19 Drug Treatment ; Adolescent ; Treatment Outcome ; *COVID-19/mortality ; Hospitalization/statistics & numerical data ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Drug Therapy, Combination ; Post-Acute COVID-19 Syndrome ; }, abstract = {This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.}, } @article {pmid38724258, year = {2024}, author = {Beale, S and Yavlinsky, A and Fong, WLE and Nguyen, VG and Kovar, J and Vos, T and Wulf Hanson, S and Hayward, AC and Abubakar, I and Aldridge, RW}, title = {Long-term outcomes of SARS-CoV-2 variants and other respiratory infections: evidence from the Virus Watch prospective cohort in England.}, journal = {Epidemiology and infection}, volume = {152}, number = {}, pages = {e77}, pmid = {38724258}, issn = {1469-4409}, support = {/WT_/Wellcome Trust/United Kingdom ; 206602/WT_/Wellcome Trust/United Kingdom ; MC_PC 19070/MRC_/Medical Research Council/United Kingdom ; MR/V028375/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; England/epidemiology ; *COVID-19/epidemiology/virology ; *SARS-CoV-2 ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; *Respiratory Tract Infections/virology/epidemiology ; Aged ; Young Adult ; Adolescent ; }, abstract = {This study compared the likelihood of long-term sequelae following infection with SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. Participants (n=5,630) were drawn from Virus Watch, a prospective community cohort investigating SARS-CoV-2 epidemiology in England. Using logistic regression, we compared predicted probabilities of developing long-term symptoms (>2 months) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. SARS-CoV-2 infection during early variant periods up to Omicron BA.1 was associated with greater probability of long-term sequalae (adjusted predicted probability (PP) range 0.27, 95% CI = 0.22-0.33 to 0.34, 95% CI = 0.25-0.43) compared with later Omicron sub-variants (PP range 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, all post-infection estimates substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00, 0.02 to 0.03, 95% CI 0.01-0.06). Variant was an important predictor of SARS-CoV-2 post-infection sequalae, with recent Omicron sub-variants demonstrating similar probabilities to other contemporaneous ARIs. Further aetiological investigation including between-pathogen comparison is recommended.}, } @article {pmid38724221, year = {2024}, author = {Smith, A and Greenwood, D and Horton, M and Osborne, T and Goodwin, M and Lawrence, RR and Winch, D and Williams, P and Milne, R and , and Sivan, M}, title = {Psychometric analysis of the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study.}, journal = {BMJ open respiratory research}, volume = {11}, number = {1}, pages = {}, pmid = {38724221}, issn = {2052-4439}, mesh = {Humans ; *Psychometrics ; *COVID-19/psychology ; Male ; Female ; Middle Aged ; Prospective Studies ; Reproducibility of Results ; Aged ; *Patient Reported Outcome Measures ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Severity of Illness Index ; Adult ; Quality of Life ; United Kingdom ; }, abstract = {BACKGROUND: Long COVID (LC) is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with LC.

OBJECTIVES: To evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with LC.

METHODS: 1314 patients attending 10 UK specialist LC clinics completed C19-YRSm and EuroQol 5D-5L (EQ-5D-5L) longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity (SS), Functional Disability (FD) and Overall Health (OH)) and internal consistency (Cronbach's alpha). Convergent validity was assessed using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Known groups validity was assessed for the Other Symptoms subscale as tertiles, as well as by hospitalisation and intensive care admission. Responsiveness and test-retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instrument's two-factor structure.

RESULTS: C19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 and 0.65 (for SS and FD), with good internal reliability (Cronbach's alphas>0.8). Item correlations between subscales ranged between 0.46 and 0.72. Convergent validity with FACIT was good (-0.46 to -0.62). The three subscales discriminated between different levels of symptom burden (p<0.001) and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) which was greater than for the EQ-5D-5L. Test-retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure.

CONCLUSIONS: The C19-YRSm is a condition-specific, reliable, valid and responsive patient-reported outcome measure for LC.}, } @article {pmid38724010, year = {2024}, author = {Wu, W and Zheng, X and Ding, H and Miao, T and Zang, Y and Shen, S and Gao, Y}, title = {Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.}, journal = {Human vaccines & immunotherapeutics}, volume = {20}, number = {1}, pages = {2345505}, pmid = {38724010}, issn = {2164-554X}, mesh = {Humans ; Cross-Sectional Studies ; *Influenza Vaccines/administration & dosage ; Male ; Female ; Middle Aged ; *COVID-19/prevention & control/epidemiology ; Europe/epidemiology ; Aged ; *Influenza, Human/prevention & control/epidemiology ; *Vaccination/statistics & numerical data ; *COVID-19 Vaccines/administration & dosage ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Aged, 80 and over ; European People ; }, abstract = {The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.}, } @article {pmid38723183, year = {2024}, author = {Falco, P and Litewczuk, D and Di Stefano, G and Galosi, E and Leone, C and De Stefano, G and Di Pietro, G and Tramontana, L and Ciardi, MR and Pasculli, P and Zingaropoli, MA and Arendt-Nielsen, L and Truini, A}, title = {Small fibre neuropathy frequently underlies the painful long-COVID syndrome.}, journal = {Pain}, volume = {165}, number = {9}, pages = {2002-2010}, doi = {10.1097/j.pain.0000000000003259}, pmid = {38723183}, issn = {1872-6623}, mesh = {Humans ; *Small Fiber Neuropathy/diagnosis/physiopathology ; Male ; Female ; Middle Aged ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Adult ; Aged ; Skin/pathology ; SARS-CoV-2 ; Biopsy ; }, abstract = {Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case-control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post-COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post-COVID-19 controls. This case-control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post-COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.}, } @article {pmid38722111, year = {2024}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Response to: Photobiomodulation in the Treatment of Dysgeusia in Patients with Long COVID: Comment.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {42}, number = {6}, pages = {437}, doi = {10.1089/pho.2024.0040}, pmid = {38722111}, issn = {2578-5478}, mesh = {Humans ; *COVID-19/complications ; *Dysgeusia/etiology ; *Low-Level Light Therapy ; SARS-CoV-2 ; }, } @article {pmid38719316, year = {2024}, author = {Sugawara, N and Tabuchi, T and Tokumitsu, K and Yasui-Furukori, N}, title = {Predictors of somatic symptoms during the COVID-19 pandemic: a national longitudinal survey in Japan.}, journal = {BMJ open}, volume = {14}, number = {5}, pages = {e082439}, pmid = {38719316}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Japan/epidemiology ; Male ; Female ; Longitudinal Studies ; Middle Aged ; Adult ; *Medically Unexplained Symptoms ; SARS-CoV-2 ; Aged ; Surveys and Questionnaires ; Pandemics ; Young Adult ; }, abstract = {OBJECTIVES: The COVID-19 pandemic has highlighted the long-term consequences of SARS-CoV-2 infection, termed long COVID. However, in the absence of comparative groups, the differentiation of disease progression remains difficult, as COVID-19 symptoms become indistinguishable from symptoms originating from alternative etiologies. This study aimed to longitudinally investigate the association between COVID-19 exposure and the somatic symptoms in the Japanese general population.

DESIGN: This was a longitudinal cohort study with 1-year follow-up.

SETTING AND PARTICIPANTS: Longitudinal data from 19 545 individuals who participated in the Japan Society and New Tobacco Internet Survey (JASTIS) 2022 and 2023 were included. In this study, we used data from the 2022 JASTIS as baseline data and the 2023 JASTIS as follow-up data. Based on questionnaire responses, respondents were classified into three categories of exposure to COVID-19.

OUTCOME MEASURES: The somatic symptoms were assessed by the Somatic Symptom Scale-8 (SSS-8). Using generalised linear models adjusted for baseline covariates, we calculated the ORs of having very high somatic symptoms assessed by SSS-8, attributable to COVID-19 exposure (no COVID-19 cases as the reference group).

RESULTS: Follow-up completers were divided into three groups according to COVID-19 exposure (no COVID-19, n=16 012; COVID-19 without O2 therapy, n=3201; COVID-19 with O2 therapy, n=332). After adjusting for all covariates, COVID-19 cases with O2 therapy had a significant positive association (OR 7.60, 95% CI 5.47 to 10.58) with a very high somatic symptoms burden while other COVID-19 exposure groups did not. Pre-existing physical and psychological conditions were also associated with increased risk of somatic symptoms.

CONCLUSION: The findings of our study suggest that the severity of COVID-19 symptoms requiring O2 therapy in the acute phase led to high somatic symptoms. Pre-existing conditions were also associated with a subsequent risk of somatic symptoms.}, } @article {pmid38718276, year = {2024}, author = {Newlands, F and Lewis, C and d'Oelsnitz, A and Pinto Pereira, SM and Stephenson, T and Chalder, T and Coughtrey, A and Dalrymple, E and Heyman, I and Harnden, A and Ford, T and Ladhani, SN and Powell, C and McOwat, K and Bhopal, R and Dudley, J and Kolasinska, P and Muhid, MZ and Nugawela, M and Rojas, NK and Shittu, A and Simmons, R and Shafran, R}, title = {"People don't have the answers": A qualitative exploration of the experiences of young people with Long COVID.}, journal = {Clinical child psychology and psychiatry}, volume = {29}, number = {3}, pages = {783-798}, pmid = {38718276}, issn = {1461-7021}, mesh = {Humans ; *COVID-19/psychology ; Adolescent ; Female ; Male ; *Qualitative Research ; Young Adult ; Post-Acute COVID-19 Syndrome ; Adaptation, Psychological ; Adult ; Health Services Accessibility ; }, abstract = {Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted (n = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study (n = 11) or its patient and public involvement and engagement (PPIE) group (n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID.}, } @article {pmid38716313, year = {2024}, author = {Yu, S and Xu, J and Yu, C and Zhang, X and Cheng, Y and Lin, D and Yan, C and Guo, M and Li, J and He, P and Cheng, W}, title = {Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.}, journal = {Cardiovascular diagnosis and therapy}, volume = {14}, number = {2}, pages = {251-263}, pmid = {38716313}, issn = {2223-3652}, abstract = {BACKGROUND: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue.

METHODS: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1β (IL-1β) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test.

RESULTS: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1β relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1β were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1β expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1β expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1β in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1β within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1β levels when compared to other patients.

CONCLUSIONS: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.}, } @article {pmid38715715, year = {2024}, author = {Mishra, SS and Pedersini, CA and Misra, R and Gandhi, TK and Rokers, B and Biswal, BB}, title = {Tracts in the limbic system show microstructural alterations post COVID-19 recovery.}, journal = {Brain communications}, volume = {6}, number = {3}, pages = {fcae139}, pmid = {38715715}, issn = {2632-1297}, abstract = {Delirium, memory loss, attention deficit and fatigue are frequently reported by COVID survivors, yet the neurological pathways underlying these symptoms are not well understood. To study the possible mechanisms for these long-term sequelae after COVID-19 recovery, we investigated the microstructural properties of white matter in Indian cohorts of COVID-recovered patients and healthy controls. For the cross-sectional study presented here, we recruited 44 COVID-recovered patients and 29 healthy controls in New Delhi, India. Using deterministic whole-brain tractography on the acquired diffusion MRI scans, we traced 20 white matter tracts and compared fractional anisotropy, axial, mean and radial diffusivity between the cohorts. Our results revealed statistically significant differences (PFWE < 0.01) in the uncinate fasciculus, cingulum cingulate, cingulum hippocampus and arcuate fasciculus in COVID survivors, suggesting the presence of microstructural abnormalities. Additionally, in a subsequent subgroup analysis based on infection severity (healthy control, non-hospitalized patients and hospitalized patients), we observed a correlation between tract diffusion measures and COVID-19 infection severity. Although there were significant differences between healthy controls and infected groups, we found no significant differences between hospitalized and non-hospitalized COVID patients. Notably, the identified tracts are part of the limbic system and orbitofrontal cortex, indicating microstructural differences in neural circuits associated with memory and emotion. The observed white matter alterations in the limbic system resonate strongly with the functional deficits reported in Long COVID. Overall, our study provides additional evidence that damage to the limbic system could be a neuroimaging signature of Long COVID. The findings identify targets for follow-up studies investigating the long-term physiological and psychological impact of COVID-19.}, } @article {pmid38715353, year = {2024}, author = {Morais, GD and Appelt, PA and Neto, EM and Bazan, R and Cabral, AM and Andrade, AO and Luvizutto, GJ and Sande de Souza, LAP}, title = {Nonlinear EEG Analysis During Motor and Cognitive Tasks in Patients With Long COVID: A Dynamic Systems Approach.}, journal = {Clinical EEG and neuroscience}, volume = {55}, number = {4}, pages = {518-525}, doi = {10.1177/15500594241252484}, pmid = {38715353}, issn = {2169-5202}, mesh = {Humans ; *COVID-19/physiopathology ; Male ; *Electroencephalography/methods ; Female ; Middle Aged ; *Cognition/physiology ; Aged ; Prospective Studies ; Brain/physiopathology ; SARS-CoV-2 ; Nonlinear Dynamics ; Adult ; }, abstract = {Introduction. Nonlinear EEG provides information about dynamic properties of the brain. This study aimed to compare nonlinear EEG parameters estimated from patients with Long COVID in different cognitive and motor tasks. Materials and Methods. This 12-month prospective cohort study included 83 patients with Long COVID: 53 symptomatic and 30 asymptomatic. Brain electrical activity was evaluated by EEG in 4 situations: (1) at rest, (2) during the Trail Making Test Part A (TMT-A), (3) during the TMT Part B (TMT-B), and (4) during a coordination task: the Box and Blocks Test (BBT). Nonlinear EEG parameters were estimated in the time domain (activity and complexity). Assessments were made at 0 to 3, 3 to 6, and 6 to 12 months after inclusion. Results. There was a decrease in activity and complexity during the TMT-A and TMT-B, and an increase of these parameters during the BBT in both groups. There was an increase in activity at rest and during the TMT-A in the COVID-19 group at 0 to 3 months compared to the control, an increase in activity in the TMT-B in the COVID-19 group at 3 to 6 months compared to the control, and reduced activity and complexity at rest and during the TMT-A at 6 to 12 months compared to the control. Conclusion. The tasks followed a pattern of increased activity and complexity in cognitive tasks, which decreased during the coordination task. It was also observed that an increase in activity at rest and during cognitive tasks in the early stages, and reduced activity and complexity at rest and during cognitive tasks in the late phases of Long COVID.}, } @article {pmid38713816, year = {2024}, author = {Baldi, F and De Rose, C and Mariani, F and Morello, R and Raffaelli, F and Valentini, P and Buonsenso, D}, title = {Cardiopulmonary Exercise Testing in Children With Long COVID: A Case-controlled Study.}, journal = {The Pediatric infectious disease journal}, volume = {43}, number = {8}, pages = {795-802}, pmid = {38713816}, issn = {1532-0987}, mesh = {Humans ; Child ; Male ; Case-Control Studies ; Female ; *COVID-19/physiopathology/diagnosis ; *Exercise Test ; Prospective Studies ; Adolescent ; SARS-CoV-2 ; Oxygen Consumption/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Cardiopulmonary exercise testing (CPET) is a noninvasive and nonexpensive diagnostic tool, that provides a comprehensive evaluation of the pulmonary, cardiovascular, and skeletal muscle systems' integrated reactions to exercise. CPET has been extensively used in adults with Long COVID (LC), while the evidence about its role in children with this condition is scarce.

METHODS: Prospective, case-controlled observational study. Children with LC and a control group of healthy children underwent CPET. CPET findings were compared within the 2 groups, and within the LC groups according to main clusters of persisting symptoms.

RESULTS: Sixty-one children with LC and 29 healthy controls were included. Overall, 90.2% of LC patients (55 of 61) had a pathologic test vs 10.3% (3/29) of the healthy control. Children with LC presented a statistically significant higher probability of having abnormal values of peak VO2 (P = 0.001), AT% pred (P <0.001), VO2/HR % (P = 0.03), VO2 work slope (P = 0.002), VE/VCO2 slope (P = 0.01). The mean VO2 peak was 30.17 (±6.85) in LC and 34.37 (±6.55) in healthy patients (P = 0.007).

CONCLUSIONS: Compared with healthy controls, children with LC have objective impaired functional capacity (expressed by a low VO2 peak), signs of deconditioning and cardiogenic inefficiency when assessed with CPET. As such, CPET should be routinely used in clinical practice to objectify and phenotype the functional limitations of children with LC, and to follow-up them.}, } @article {pmid38713673, year = {2024}, author = {Gross, RS and Thaweethai, T and Rosenzweig, EB and Chan, J and Chibnik, LB and Cicek, MS and Elliott, AJ and Flaherman, VJ and Foulkes, AS and Gage Witvliet, M and Gallagher, R and Gennaro, ML and Jernigan, TL and Karlson, EW and Katz, SD and Kinser, PA and Kleinman, LC and Lamendola-Essel, MF and Milner, JD and Mohandas, S and Mudumbi, PC and Newburger, JW and Rhee, KE and Salisbury, AL and Snowden, JN and Stein, CR and Stockwell, MS and Tantisira, KG and Thomason, ME and Truong, DT and Warburton, D and Wood, JC and Ahmed, S and Akerlundh, A and Alshawabkeh, AN and Anderson, BR and Aschner, JL and Atz, AM and Aupperle, RL and Baker, FC and Balaraman, V and Banerjee, D and Barch, DM and Baskin-Sommers, A and Bhuiyan, S and Bind, MC and Bogie, AL and Bradford, T and Buchbinder, NC and Bueler, E and Bükülmez, H and Casey, BJ and Chang, L and Chrisant, M and Clark, DB and Clifton, RG and Clouser, KN and Cottrell, L and Cowan, K and D'Sa, V and Dapretto, M and Dasgupta, S and Dehority, W and Dionne, A and Dummer, KB and Elias, MD and Esquenazi-Karonika, S and Evans, DN and Faustino, EVS and Fiks, AG and Forsha, D and Foxe, JJ and Friedman, NP and Fry, G and Gaur, S and Gee, DG and Gray, KM and Handler, S and Harahsheh, AS and Hasbani, K and Heath, AC and Hebson, C and Heitzeg, MM and Hester, CM and Hill, S and Hobart-Porter, L and Hong, TKF and Horowitz, CR and Hsia, DS and Huentelman, M and Hummel, KD and Irby, K and Jacobus, J and Jacoby, VL and Jone, PN and Kaelber, DC and Kasmarcak, TJ and Kluko, MJ and Kosut, JS and Laird, AR and Landeo-Gutierrez, J and Lang, SM and Larson, CL and Lim, PPC and Lisdahl, KM and McCrindle, BW and McCulloh, RJ and McHugh, K and Mendelsohn, AL and Metz, TD and Miller, J and Mitchell, EC and Morgan, LM and Müller-Oehring, EM and Nahin, ER and Neale, MC and Ness-Cochinwala, M and Nolan, SM and Oliveira, CR and Osakwe, O and Oster, ME and Payne, RM and Portman, MA and Raissy, H and Randall, IG and Rao, S and Reeder, HT and Rosas, JM and Russell, MW and Sabati, AA and Sanil, Y and Sato, AI and Schechter, MS and Selvarangan, R and Sexson Tejtel, SK and Shakti, D and Sharma, K and Squeglia, LM and Srivastava, S and Stevenson, MD and Szmuszkovicz, J and Talavera-Barber, MM and Teufel, RJ and Thacker, D and Trachtenberg, F and Udosen, MM and Warner, MR and Watson, SE and Werzberger, A and Weyer, JC and Wood, MJ and Yin, HS and Zempsky, WT and Zimmerman, E and Dreyer, BP and , }, title = {Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0285635}, pmid = {38713673}, issn = {1932-6203}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/virology ; Adolescent ; Child ; Child, Preschool ; Female ; Young Adult ; Adult ; Male ; Infant ; SARS-CoV-2/isolation & purification ; Infant, Newborn ; Prospective Studies ; Research Design ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.

CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.}, } @article {pmid38713158, year = {2024}, author = {Manglani, R and Fenster, M and Henson, T and Jain, A and Schluger, N}, title = {Clinical characteristics, imaging, and lung function among patients with persistent dyspnea of COVID-19: a retrospective observational cohort study.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {}, number = {}, pages = {}, doi = {10.4081/monaldi.2024.2733}, pmid = {38713158}, issn = {2532-5264}, abstract = {The available medical literature on lung function and corresponding clinical characteristics among symptomatic survivors of Corona Virus Disease 2019 (long COVID) is sparse. Primary physicians referred patients who manifested persistent dyspnea months after their index case of infection to a designated clinic. Patients underwent symptom-driven, quality-of-life, physical, and focused respiratory [pulmonary function tests and computed tomography (CT) of the chest] evaluations and were followed over time. In this paper, we present our findings. Patients with abnormal CT imaging were more likely to be of advanced age and to have been hospitalized during their COVID-19 infection. Forced exhaled volume in the first second, forced vital capacity (FVC), total lung capacity, and diffusion capacity of carbon monoxide measurements were found to be significantly lower in patients with abnormal CT imaging. Multivariate regression of clinical characteristics uncovered a significant association between FVC, body mass index, history of hospitalization, and diabetes mellitus. In conclusion, longer-term studies will help further our understanding of the risk factors, disease course, and prognosis of long COVID patients.}, } @article {pmid38712261, year = {2024}, author = {Wentz, E and Ni, Z and Yenokyan, K and Vergara, C and Pahwa, J and Kammerling, T and Xiao, P and Duggal, P and Lau, B and Mehta, SH}, title = {Cohort profile: the Johns Hopkins COVID Long Study (JHCLS), a United States Nationwide Prospective Cohort Study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38712261}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, abstract = {PURPOSE: COVID-19 disease continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short- and long-term consequences of COVID-19 disease in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey.

PARTICIPANTS: Sixteen thousand, seven hundred sixty-four adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey.

FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16,764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported a hospitalization, and 63% were defined as having long COVID using the WHO definition.

FUTURE PLANS: Analysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.}, } @article {pmid38711990, year = {2024}, author = {Zifko, U and Guendling, K and Seet, R and Kasper, S}, title = {Management of cognitive impairment associated with post-COVID-19 syndrome: recommendations for primary care.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1338235}, pmid = {38711990}, issn = {1663-9812}, abstract = {Introduction: Although post-COVID-19 syndrome (PCS) with cognitive impairment is increasingly encountered in primary care, evidence-based recommendations for its appropriate management are lacking. Methods: A systematic literature search evaluating the diagnosis and treatment of cognitive impairment associated with PCS was conducted. Practical recommendations for the management of PCS-associated cognitive impairment in primary care are summarized, based on an evaluation of pharmacological plausibility and clinical applications. Results: Currently, the pathology of cognitive impairment associated with PCS remains unclear with no high-quality data to support targeted interventions. Existing treatment approaches are directed towards symptom relief where counseling on the chronicity of the disease and regular reassessments at 4- to 8-week intervals is considered reasonable. Patients should be informed and encouraged to adopt a healthy lifestyle that centers around balanced nutrition and appropriate physical activities. They may also benefit from the intake of vitamins, micronutrients, and probiotics. The administration of Ginkgo biloba extract could offer a safe and potentially beneficial treatment option. Other non-pharmacological measures include physiotherapy, digitally supported cognitive training, and, if indicated, ergotherapy or speech therapy. In most patients, symptoms improve within 8 weeks. If serious, ambiguous, or when new symptoms occur, specialized diagnostic measures such as comprehensive neurocognitive testing or neuroimaging should be initiated. Very few patients would require inpatient rehabilitation. Conclusion: PCS with cognitive impairment is a debilitating condition that could affect daily functioning and reduce work productivity. Management in primary care should adopt a multidisciplinary approach, centering around physical, cognitive, and pharmacological therapies.}, } @article {pmid38710760, year = {2024}, author = {Gietl, M and Burkert, F and Hofer, S and Gostner, JM and Sonnweber, T and Tancevski, I and Pizzini, A and Sahanic, S and Schroll, A and Brigo, N and Egger, A and Bellmann-Weiler, R and Löffler-Ragg, J and Weiss, G and Kurz, K}, title = {Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {10388}, pmid = {38710760}, issn = {2045-2322}, support = {GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; GZ 75759//TYROLEAN REGIONAL GOVERNMENT/ ; }, mesh = {Humans ; *COVID-19/blood/complications/diagnosis ; Female ; Male ; Middle Aged ; *Severity of Illness Index ; *Biomarkers/blood ; *SARS-CoV-2/isolation & purification ; Aged ; Adult ; Physical Functional Performance ; Interleukin-6/blood ; C-Reactive Protein/metabolism/analysis ; Inflammation ; Tryptophan/blood/metabolism ; Neopterin/blood ; Phenylalanine/blood/metabolism ; Amino Acids/blood ; }, abstract = {Research into the molecular basis of disease trajectory and Long-COVID is important to get insights toward underlying pathophysiological processes. The objective of this study was to investigate inflammation-mediated changes of metabolism in patients with acute COVID-19 infection and throughout a one-year follow up period. The study enrolled 34 patients with moderate to severe COVID-19 infection admitted to the University Clinic of Innsbruck in early 2020. The dynamics of multiple laboratory parameters (including inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), neopterin] as well as amino acids [tryptophan (Trp), phenylalanine (Phe) and tyrosine (Tyr)], and parameters of iron and vitamin B metabolism) was related to disease severity and patients' physical performance. Also, symptom load during acute illness and at approximately 60 days (FU1), and one year after symptom onset (FU2) were monitored and related with changes of the investigated laboratory parameters: During acute infection many investigated laboratory parameters were elevated (e.g., inflammatory markers, ferritin, kynurenine, phenylalanine) and enhanced tryptophan catabolism and phenylalanine accumulation were found. At FU2 nearly all laboratory markers had declined back to reference ranges. However, kynurenine/tryptophan ratio (Kyn/Trp) and the phenylalanine/tyrosine ratio (Phe/Tyr) were still exceeding the 95th percentile of healthy controls in about two thirds of our cohort at FU2. Lower tryptophan concentrations were associated with B vitamin availability (during acute infection and at FU1), patients with lower vitamin B12 levels at FU1 had a prolonged and more severe impairment of their physical functioning ability. Patients who had fully recovered (ECOG 0) presented with higher concentrations of iron parameters (ferritin, hepcidin, transferrin) and amino acids (phenylalanine, tyrosine) at FU2 compared to patients with restricted ability to work. Persistent symptoms at FU2 were tendentially associated with IFN-γ related parameters. Women were affected by long-term symptoms more frequently. Conclusively, inflammation-mediated biochemical changes appear to be related to symptoms of patients with acute and Long Covid.}, } @article {pmid38710681, year = {2024}, author = {Naidu, AS and Wang, CK and Rao, P and Mancini, F and Clemens, RA and Wirakartakusumah, A and Chiu, HF and Yen, CH and Porretta, S and Mathai, I and Naidu, SAG}, title = {Author Correction: Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.}, journal = {NPJ science of food}, volume = {8}, number = {1}, pages = {26}, doi = {10.1038/s41538-024-00267-w}, pmid = {38710681}, issn = {2396-8370}, } @article {pmid38708693, year = {2024}, author = {Sadat Larijani, M and Bavand, A and Banifazl, M and Ashrafian, F and Moradi, L and Ramezani, A}, title = {Determination of COVID-19 Late Disorders as Possible Long-COVID and/or Vaccination Consequences.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241251941}, pmid = {38708693}, issn = {2150-1327}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/prevention & control/epidemiology ; *COVID-19 Vaccines/adverse effects/administration & dosage ; Immunization, Secondary ; Iran/epidemiology ; SARS-CoV-2 ; Vaccination/adverse effects/statistics & numerical data ; *Post-Acute COVID-19 Syndrome ; }, abstract = {In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.}, } @article {pmid38708532, year = {2024}, author = {Rinnenburger, D}, title = {[Breathless, without strength, forgetful: Long Covid, the pandemic within the pandemic.].}, journal = {Recenti progressi in medicina}, volume = {115}, number = {5}, pages = {215-217}, doi = {10.1701/4262.42400}, pmid = {38708532}, issn = {2038-1840}, mesh = {Humans ; *COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome ; Pandemics ; Memory Disorders/etiology/epidemiology ; }, abstract = {Following the Covid-19 pandemic, a new disease has emerged: Long Covid syndrome, about which we know little and on which too little research is being done. It is a chronic disease, which is diagnosed when Covid symptoms last more than 12 weeks. To date, there is no pharmacological or other approach to Long Covid. The main symptoms of Long Covid are pain similar to those of rheumatic and autoimmune diseases, headaches, concentration and memory disorders, sometimes also perceived as brain fog and fatigue. Research and education and sensible, bipartisan social policy, away from all ideologies, are needed to address this additional aspect of the SARS-CoV-2 pandemic.}, } @article {pmid38707697, year = {2024}, author = {Yamamoto, K and Nakagawa, K and Otsuka, F}, title = {Idiopathic ventricular tachycardia detected after coronavirus disease 2019.}, journal = {Journal of general and family medicine}, volume = {25}, number = {3}, pages = {164-165}, pmid = {38707697}, issn = {2189-7948}, abstract = {We present a 23-year-old woman with depression and long COVID in whom a diagnosis of idiopathic ventricular tachycardia (VT) was made. Although the relationship between idiopathic VT and long COVID remains unknown, this is the first report of idiopathic VT detected in a patient with long COVID.}, } @article {pmid38707018, year = {2024}, author = {Shweikeh, F and Hong, G and Rabeeah, S and Shabir, U and Sofi, A}, title = {COVID-19 and Its Sequelae Masquerading as Gastrointestinal Ailments: A Report of Gastroesophageal Reflux Disease (GERD) and Review of Recent Cases.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e57617}, pmid = {38707018}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) predominantly causes respiratory symptoms. However, a rare segment of patients recovering from COVID-19 may develop gastrointestinal (GI) symptoms. We describe a case of a female who presented with symptoms suggestive of refractory gastroesophageal reflux disease (GERD) for 18 months following COVID-19 infection. Her symptoms included epigastric and chest pain, coughing, and vomiting. Upper endoscopy and 24-hour pH monitoring were negative. Following hospital admission due to worsening symptoms, she was diagnosed with chronic pulmonary embolism (PE) presumed to be related to COVID-19. Her reflux symptoms resolved within two days of the initiation of anticoagulation. Our findings suggest that chronic PE should be considered in patients presenting with GERD refractory to treatment following COVID-19 infection. Generally, as COVID-19 and its sequelae may masquerade as GI conditions, they should be on the differential diagnosis, especially in the post-pandemic era when routine testing has significantly declined.}, } @article {pmid38704055, year = {2024}, author = {Altmayer, S and Leung, AN and de Oliveira, GS and Prodigios, J and Patel, P and Mohammed, TL and Verma, N and Hochhegger, B}, title = {Chronic Chest Computed Tomography Findings Following COVID-19 Pneumonia.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {298-308}, doi = {10.1053/j.sult.2024.02.008}, pmid = {38704055}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Tomography, X-Ray Computed/methods ; *SARS-CoV-2 ; *Lung/diagnostic imaging ; Radiography, Thoracic/methods ; }, abstract = {Respiratory symptoms are a frequent manifestation of patients with post-acute sequela of SARS-CoV-2 (PASC), also known as long-COVID. Many cohorts of predominantly hospitalized patients have shown that a significant subset may have persistent chest computed tomography findings for more than 12 months after the acute infection. Proper understanding of the evolving long-term imaging findings and terminology is crucial for accurate imaging interpretation and patient care. The goal of this article is to review the chronic chest computed tomography findings of patients with PASC and common pitfalls.}, } @article {pmid38700929, year = {2024}, author = {Maripuri, M and Dey, A and Honerlaw, J and Hong, C and Ho, YL and Tanukonda, V and Chen, AW and Panickan, VA and Wang, X and Zhang, HG and Yang, D and Samayamuthu, MJ and Morris, M and Visweswaran, S and Beaulieu-Jones, B and Ramoni, R and Muralidhar, S and Gaziano, JM and Liao, K and Xia, Z and Brat, GA and Cai, T and Cho, K}, title = {Characterization of Post-COVID-19 Definitions and Clinical Coding Practices: Longitudinal Study.}, journal = {Online journal of public health informatics}, volume = {16}, number = {}, pages = {e53445}, pmid = {38700929}, issn = {1947-2579}, support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Post-COVID-19 condition (colloquially known as "long COVID-19") characterized as postacute sequelae of SARS-CoV-2 has no universal clinical case definition. Recent efforts have focused on understanding long COVID-19 symptoms, and electronic health record (EHR) data provide a unique resource for understanding this condition. The introduction of the International Classification of Diseases, Tenth Revision (ICD-10) code U09.9 for "Post COVID-19 condition, unspecified" to identify patients with long COVID-19 has provided a method of evaluating this condition in EHRs; however, the accuracy of this code is unclear.

OBJECTIVE: This study aimed to characterize the utility and accuracy of the U09.9 code across 3 health care systems-the Veterans Health Administration, the Beth Israel Deaconess Medical Center, and the University of Pittsburgh Medical Center-against patients identified with long COVID-19 via a chart review by operationalizing the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) definitions.

METHODS: Patients who were COVID-19 positive with either a U07.1 ICD-10 code or positive polymerase chain reaction test within these health care systems were identified for chart review. Among this cohort, we sampled patients based on two approaches: (1) with a U09.9 code and (2) without a U09.9 code but with a new onset long COVID-19-related ICD-10 code, which allows us to assess the sensitivity of the U09.9 code. To operationalize the long COVID-19 definition based on health agency guidelines, symptoms were grouped into a "core" cluster of 11 commonly reported symptoms among patients with long COVID-19 and an extended cluster that captured all other symptoms by disease domain. Patients having ≥2 symptoms persisting for ≥60 days that were new onset after their COVID-19 infection, with ≥1 symptom in the core cluster, were labeled as having long COVID-19 per chart review. The code's performance was compared across 3 health care systems and across different time periods of the pandemic.

RESULTS: Overall, 900 patient charts were reviewed across 3 health care systems. The prevalence of long COVID-19 among the cohort with the U09.9 ICD-10 code based on the operationalized WHO definition was between 23.2% and 62.4% across these health care systems. We also evaluated a less stringent version of the WHO definition and the CDC definition and observed an increase in the prevalence of long COVID-19 at all 3 health care systems.

CONCLUSIONS: This is one of the first studies to evaluate the U09.9 code against a clinical case definition for long COVID-19, as well as the first to apply this definition to EHR data using a chart review approach on a nationwide cohort across multiple health care systems. This chart review approach can be implemented at other EHR systems to further evaluate the utility and performance of the U09.9 code.}, } @article {pmid38700879, year = {2024}, author = {Cogliandro, V and Bonfanti, P}, title = {Long COVID: lights and shadows on the clinical characterization of this emerging pathology.}, journal = {The new microbiologica}, volume = {47}, number = {1}, pages = {15-27}, pmid = {38700879}, issn = {1121-7138}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Fatigue Syndrome, Chronic/virology ; Risk Factors ; Quality of Life ; Postural Orthostatic Tachycardia Syndrome/physiopathology ; }, abstract = {More than 800 million individuals have contracted SARSCOV2 infection worldwide. It was estimated that almost 10-20% of these might suffer from Long COVID. It is a multisystemic syndrome, which negatively affects the quality of life with a significant burden of health loss compared to COVID negative individuals. Moreover, the risk of sequelae still remains high at 2 years in both nonhospitalized and hospitalized individuals. This review summarizes studies regarding long COVID and clarifies the definitions, the risk factors and the management of this syndrome. Finally, it delves into the most frequent long-term outcomes, especially postural orthostatic tachycardia syndrome" (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), brain fog, and their therapeutical possibilities.}, } @article {pmid38700658, year = {2024}, author = {Degli Antoni, M and Maifredi, G and Storti, S and Tiecco, G and Di Gregorio, M and Rossi, B and Gasparotti, C and Focà, E and Castelli, F and Quiros-Roldan, E}, title = {Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV.}, journal = {Infection}, volume = {52}, number = {6}, pages = {2339-2350}, pmid = {38700658}, issn = {1439-0973}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Retrospective Studies ; Middle Aged ; *HIV Infections/epidemiology/complications ; Italy/epidemiology ; Adult ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Aged ; Incidence ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence.

METHODS: We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models.

RESULTS: In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7-39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99-3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99-3.66). Notably, no viro-immunological variable modified the PCCs risk onset.

CONCLUSIONS: Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.}, } @article {pmid38700307, year = {2023}, author = {Karuturi, S}, title = {Long COVID-19: A Systematic Review.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {9}, pages = {82-94}, doi = {10.59556/japi.71.0337}, pmid = {38700307}, issn = {0004-5772}, mesh = {Humans ; COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/pathology/therapy ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019's (COVID-19's) wide dissemination casts long-term health jeopardy for millions. Long COVID-19, a lingering multisystem malady, weaves a complex array of symptoms. Understanding its full impact requires extensive research over months or years. The pace of recovery remains uncertain, challenging healthcare systems. An evidence-based symphony of medical care and support is urgently needed for long haulers. Understanding long COVID's genesis and advocating for patients is vital. Our comprehension remains limited, prompting a systematic scoping study to explore the existing knowledge and pave the way for future research, illuminating the enigma of "long COVID" and guiding the path towards understanding this relentless condition. How to cite this article: Karuturi S. Long COVID-19: A Systematic Review. J Assoc Physicians India 2023;71(9):82-94.}, } @article {pmid38699316, year = {2024}, author = {Azhir, A and Hügel, J and Tian, J and Cheng, J and Bassett, IV and Bell, DS and Bernstam, EV and Farhat, MR and Henderson, DW and Lau, ES and Morris, M and Semenov, YR and Triant, VA and Visweswaran, S and Strasser, ZH and Klann, JG and Murphy, SN and Estiri, H}, title = {Precision Phenotyping for Curating Research Cohorts of Patients with Post-Acute Sequelae of COVID-19 (PASC) as a Diagnosis of Exclusion.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.13.24305771}, pmid = {38699316}, abstract = {Scalable identification of patients with the post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms and the suboptimal accuracy, demographic biases, and underestimation of the PASC diagnosis code (ICD-10 U09.9). In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying research cohorts of PASC patients, defined as a diagnosis of exclusion. We used longitudinal electronic health records (EHR) data from over 295 thousand patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to exclude sequelae that prior conditions can explain. We performed independent chart reviews to tune and validate our precision phenotyping algorithm. Our PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying Long COVID patients compared to the U09.9 diagnosis code. Our algorithm identified a PASC research cohort of over 24 thousand patients (compared to about 6 thousand when using the U09.9 diagnosis code), with a 79.9 percent precision (compared to 77.8 percent from the U09.9 diagnosis code). Our estimated prevalence of PASC was 22.8 percent, which is close to the national estimates for the region. We also provide an in-depth analysis outlining the clinical attributes, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC. The PASC phenotyping method presented in this study boasts superior precision, accurately gauges the prevalence of PASC without underestimating it, and exhibits less bias in pinpointing Long COVID patients. The PASC cohort derived from our algorithm will serve as a springboard for delving into Long COVID's genetic, metabolomic, and clinical intricacies, surmounting the constraints of recent PASC cohort studies, which were hampered by their limited size and available outcome data.}, } @article {pmid38697866, year = {2024}, author = {Korapatti, C and Vera, L and Miller, K}, title = {Biosound Therapy as a treatment for long COVID patients: A pre-post pilot study.}, journal = {Explore (New York, N.Y.)}, volume = {20}, number = {5}, pages = {103000}, doi = {10.1016/j.explore.2024.04.004}, pmid = {38697866}, issn = {1878-7541}, mesh = {Humans ; Pilot Projects ; *COVID-19/therapy ; Middle Aged ; Male ; Adult ; Female ; Aged ; SARS-CoV-2 ; Biofeedback, Psychology/methods ; Post-Acute COVID-19 Syndrome ; Anxiety/therapy ; Music Therapy/methods ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: 43 % of people who are diagnosed with COVID-19 will experience persistent symptoms, also known as "long COVID," which lasts past the recovery of the acute infection. Long COVID symptoms overlap with symptoms that the Biosound Therapy System (BTS) has been shown to improve. The BTS is a multimodal treatment that includes biofeedback, vibroacoustic therapy synchronized with music that plays binaural beats, and video content. This study aimed to determine feasibility for a future full-scale Randomized Controlled Trial (RCT) and explore the impact of the BTS on long COVID symptoms.

METHODS: This pre-post pilot study was conducted in an outpatient mental health clinic. Adults aged 20-65 years old with persistent COVID-19 symptoms were screened and randomly assigned to the intervention or control group. The intervention group was given 8 Biosound Therapy sessions during a period of 4 weeks. All participants were assessed at baseline and at post-intervention using the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7), Cambridge Brain Sciences (CBS) tasks, and the COVID-19 Persistent Symptom Questionnaire. The feasibility outcomes were recruitment rates, retention rates, and open-ended questions about participants' experiences.

RESULTS: 15 participants enrolled in the study and 13 completed the study (9 intervention, 4 control). Trial recruitment ended prematurely due to the emergence of the Omicron variant of COVID-19. Participants responded to open-ended questions with only positive remarks and made no comments on the study not being feasible. A Wilcoxon signed-rank test indicated that compared to baseline, participants in the intervention group had significant improvement in their GAD-7 score, PHQ9 score, 2 Cambridge Brain Science tasks ("Odd" and "Double Trouble"), fatigue, and difficulties in concentrating or remembering (p < 0.05; 95 % CI).

CONCLUSION: The intervention group showed promising improvement without reported side effects. A full-scale RCT is feasible as long as the recruitment setting is changed to a location that allows access to more patients with long COVID. Results were limited due to the small sample size; therefore, a full-scale trial is needed.}, } @article {pmid38697594, year = {2024}, author = {Chao, TC and Chiang, SL and Lai, CY and Huang, CY and Lee, MS and Lin, CH and Chang, CC and Lin, CH}, title = {Association Between Physical Activity Amount and Cardiorespiratory Fitness, Sleep Quality, and Health-Related Quality of Life in Patients With Long COVID: A Cross-sectional Study.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {9}, pages = {1673-1681}, doi = {10.1016/j.apmr.2024.04.010}, pmid = {38697594}, issn = {1532-821X}, mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Quality of Life ; *COVID-19 ; *Cardiorespiratory Fitness/physiology ; *Exercise ; Adult ; Middle Aged ; *Sleep Quality ; Sex Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Age Factors ; }, abstract = {OBJECTIVE: To investigate the association between physical activity (PA) amount and gender differences on cardiorespiratory fitness (CRF), sleep quality, and health-related quality of life (HRQoL) in individuals with long COVID.

DESIGN: Cross-sectional study.

SETTING: An integrated outpatient clinic for post-COVID-19 at a medical center.

PARTICIPANTS: Convenience sample of patients (N=264) diagnosed with long COVID.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: PA amounts, sleep quality, and HRQoL were measured by the International Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, and the World Health Organization Questionnaire on Quality of Life: Short Form, respectively. CRF was evaluated through graded exercise testing.

RESULTS: The participants had a mean age of 42.5±13.5 years and a mean duration of post-COVID-19 symptoms of 12.7±6.8 weeks. More than half (n=149, 56.5%) were female patients. Female participants had significantly lower CRF than male participants (P<.05). Older age and higher body mass index were associated with worse CRF and HRQoL (P<.05). Less sitting behavior and greater amounts of vigorous-intensity PA (VPA) or total PA were associated with better CRF (P<.05). In addition, greater total PA and moderate-intensity PA (MPA) were associated with better sleep quality and HRQoL (P<.05), respectively.

CONCLUSIONS: Gender differences were found in CRF among patients with long COVID. Greater self-reported VPA or total PA was associated with better CRF, whereas greater total PA and MPA were associated with better sleep quality and HRQoL, respectively, in patients with long COVID. Further research is needed to explore these associations in longitudinal studies.}, } @article {pmid38696415, year = {2024}, author = {Hua, MJ and Butera, G and Akinyemi, O and Porterfield, D}, title = {Biases and limitations in observational studies of Long COVID prevalence and risk factors: A rapid systematic umbrella review.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0302408}, pmid = {38696415}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Risk Factors ; Prevalence ; *SARS-CoV-2/isolation & purification ; *Observational Studies as Topic ; Bias ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Observational studies form the foundation of Long COVID knowledge, however combining data from Long COVID observational studies has multiple methodological challenges. This umbrella review synthesizes estimates of Long COVID prevalence and risk factors as well as biases and limitations in the primary and review literatures.

METHODS AND FINDINGS: A systematic literature search was conducted using multiple electronic databases (PubMed, EMBASE, LitCOVID) from Jan 1, 2019 until June 9, 2023. Eligible studies were systematic reviews including adult populations assessed for at least one Long COVID symptom four weeks or more after SARS-CoV-2 infection. Overall and subgroup prevalence and risk factors as well as risk of bias (ROB) assessments were extracted and descriptively analyzed. The protocol was registered with PROSPERO (CRD42023434323). Fourteen reviews of 5-196 primary studies were included: 8 reported on Long COVID prevalence, 5 on risk/protective factors, and 1 on both. Prevalence of at least 1 Long COVID symptom ranged from 21% (IQR: 8.9%-35%) to 74.5% (95% CI: 55.6%-78.0%). Risk factor reviews found significant associations between vaccination status, sex, acute COVID-19 severity, and comorbidities. Both prevalence and risk factor reviews frequently identified selection and ascertainment biases. Using the AMSTAR 2 criteria, the quality of included reviews, particularly the prevalence reviews, were concerning for the adequacy of ROB assessments and justifications for conducting meta-analysis.

CONCLUSION: A high level of heterogeneity render the interpretation of pooled prevalence estimates of Long COVID challenging, further hampered by the lack of robust critical appraisals in the included reviews. Risk factor reviews were of higher quality overall and suggested consistent associations between Long COVID risk and patient characteristics.}, } @article {pmid38695969, year = {2024}, author = {Gorenshtein, A and Liba, T and Leibovitch, L and Stern, S and Stern, Y}, title = {Intervention modalities for brain fog caused by long-COVID: systematic review of the literature.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {7}, pages = {2951-2968}, pmid = {38695969}, issn = {1590-3478}, mesh = {Humans ; Brain ; *Cognitive Dysfunction/etiology/therapy/physiopathology ; COVID-19/complications ; Hyperbaric Oxygenation/methods ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; Transcranial Direct Current Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; *Mental Fatigue/therapy ; }, abstract = {Individuals suffering from long-COVID can present with "brain fog", which is characterized by a range of cognitive impairments, such as confusion, short-term memory loss, and difficulty concentrating. To date, several potential interventions for brain fog have been considered. Notably, no systematic review has comprehensively discussed the impact of each intervention type on brain fog symptoms. We included studies on adult (aged > 18 years) individuals with proven long- COVID brain-fog symptoms from PubMed, MEDLINE, Central, Scopus, and Embase. A search limit was set for articles published between 01/2020 and 31/12/2023. We excluded studies lacking an objective assessment of brain fog symptoms and patients with preexisting neurological diseases that affected cognition before COVID-19 infection. This review provided relevant information from 17 studies. The rehabilitation studies utilized diverse approaches, leading to a range of outcomes in terms of the effectiveness of the interventions. Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments.}, } @article {pmid38695877, year = {2024}, author = {Finsterer, J}, title = {All available diagnostic and therapeutic options should be fully exploited in order to quickly identify and optimally treat neuropathic pain in long-COVID.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {38695877}, issn = {1433-8491}, } @article {pmid38695461, year = {2024}, author = {Batista, KBC and Fernandez, MV and Barberia, LG and Silva, ETD and Pedi, VD and Pontes, BMLM and Araujo, G and Moreira, RDS and Pedrosa, M and Verotti, MP and Henriques, CMP and Florêncio, AC and Amorim, MMR}, title = {[Overview of long COVID in Brazil: a preliminary analysis of a survey to think about health policies].}, journal = {Cadernos de saude publica}, volume = {40}, number = {4}, pages = {e00094623}, pmid = {38695461}, issn = {1678-4464}, mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/prevention & control ; Adult ; Female ; Male ; *Post-Acute COVID-19 Syndrome ; *Health Policy ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2 ; Quality of Life ; Young Adult ; Aged ; Socioeconomic Factors ; Adolescent ; }, abstract = {Characterized by symptoms that remain or appear for the first time within three months of SARS-CoV-2 infection, long COVID can manifest itself in different ways, including in non-hospitalized or asymptomatic cases. Thus, this study offers an overview of long COVID in Brazil, especially of its diagnosis, symptoms, and challenges for new health management. Data from a study that investigated long COVID in people affected by COVID-19 were used. These original data stem from a survey with adult Brazilians (aged 18 years or older) who had COVID-19 that collected information from March 14 to April 14, 2022, by a questionnaire on social media. The questionnaire addressed sociodemographic characteristics, history of COVID-19 infections, vaccination against the disease, investigation of health status and quality of life before and after COVID-19, and search and access to treatment. Of the 1,728 respondents, 720 were considered eligible for analysis, of which 496 (69%) had long COVID. Individuals with long COVID reported clinical manifestations such as anxiety (80%), memory loss (78%), generalized pain (77%), lack of attention (75%), fatigue (73%), hair loss (71%), sleep changes (70%), mood swings (62%), malaise (60%), and joint pain (59%). Most sought health services during and after the acute phase of COVID-19 (94 and 80%, respectively), representing the need to structure the healthcare system for these patients.}, } @article {pmid38694270, year = {2024}, author = {Xavier de Brito, AS and Bronchtein, AI and Schaustz, EB and Glavam, AP and Pinheiro, MVT and Secco, JCP and Camargo, GC and Almeida, SA and Quintella, TA and Albuquerque, DC and Luiz, RR and Medei, E and Souza, OF and Sales, ARK and Sousa, AS and Rosado-de-Castro, PH and Moll-Bernardes, RJ}, title = {Value of [123]I-MIBG SPECT for the assessment of dysautonomia in patients with long COVID.}, journal = {International journal of cardiology. Heart & vasculature}, volume = {52}, number = {}, pages = {101413}, pmid = {38694270}, issn = {2352-9067}, } @article {pmid38693641, year = {2024}, author = {Apostolou, E and Rosén, A}, title = {Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.}, journal = {Journal of internal medicine}, volume = {296}, number = {1}, pages = {93-115}, doi = {10.1111/joim.13792}, pmid = {38693641}, issn = {1365-2796}, support = {4.3-2019-00201 GD-2020-138//Swedish Research Council/ ; 211832Pj01H2//Swedish Cancer Society/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/virology/genetics ; *Epigenesis, Genetic ; Virus Latency/genetics ; Herpesvirus 4, Human ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances-among a spectrum of symptoms-that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent-lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses-particularly Epstein-Barr virus-may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.}, } @article {pmid38693436, year = {2024}, author = {Văcăraş, V and Vulturar, R and Chiş, A and Damian, L}, title = {Inclusion body myositis, viral infections, and TDP-43: a narrative review.}, journal = {Clinical and experimental medicine}, volume = {24}, number = {1}, pages = {91}, pmid = {38693436}, issn = {1591-9528}, mesh = {*Myositis, Inclusion Body/virology ; Humans ; *Virus Diseases/immunology/virology ; *DNA-Binding Proteins/genetics/metabolism ; }, abstract = {The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.}, } @article {pmid38693285, year = {2024}, author = {Pinto Pereira, SM and Nugawela, MD and Stephenson, T and Foret-Bruno, P and Dalrymple, E and Xu, L and Whittaker, E and Heyman, I and Ford, T and Segal, T and Chalder, T and Ladhani, SN and Mensah, AA and McOwat, K and Simmons, R and , and Shafran, R}, title = {Post-Covid-19 condition (Long Covid) in children and young people 12 months after infection or reinfection with the Omicron variant: a prospective observational study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9957}, pmid = {38693285}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/virology/complications/epidemiology ; Child ; *SARS-CoV-2/isolation & purification ; Adolescent ; Male ; Female ; *Reinfection/virology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {Our previous study in children and young people (CYP) at 3- and 6-months post-infection showed that 12-16% of those infected with the Omicron (B.1.1.529) variant of SARS-CoV-2 met the research definition of Long Covid, with no differences between first-positive and reinfected CYP. The primary objective of the current study is to explore the impact of the Omicron variant of SARS-CoV-2 infection on young people 12 months post infection. 345 CYP aged 11-17 years with a first laboratory-confirmed infection with the Omicron variant and 360 CYP reinfected with the Omicron variant completed an online questionnaire assessing demographics, symptoms, and their impact shortly after testing and again at 3-, 6-and 12-months post-testing. Vaccination status was determined from information held at UKHSA. Comparisons between groups were made using chi-squared, Mann-Whitney U, and Kruskal-Wallis tests. The most common symptoms in first-positive and reinfected CYP 12-months post-testing were tiredness (35.7 and 33.6% respectively) and sleeping difficulties (27.5 and 28.3% respectively). Symptom profiles, severity and impact were similar in the two infection status groups. Overall, by 12-months, 17.4% of first-positives and 21.9% of reinfected CYP fulfilled the research consensus Long Covid definition (p = 0.13). 12-months post Omicron infection, there is little difference between first-positive and reinfected CYP with respect to symptom profiles and impact. Clinicians may not therefore need to consider number of infections and type of variant when developing treatment plans. Further studies are needed to assess causality of reported symptoms up to 12-months after SARS-CoV-2 infection.}, } @article {pmid38692805, year = {2024}, author = {Borczuk, AC}, title = {Pathology of COVID-19 Lung Disease.}, journal = {Surgical pathology clinics}, volume = {17}, number = {2}, pages = {203-214}, doi = {10.1016/j.path.2023.11.006}, pmid = {38692805}, issn = {1875-9157}, mesh = {Humans ; *COVID-19/pathology/complications ; *Lung/pathology ; *SARS-CoV-2 ; Lung Diseases/pathology ; }, abstract = {The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.}, } @article {pmid38691776, year = {2024}, author = {Kurakh, AV and Ahii, VI and Chopey, IV and Hechko, MM and Chubirko, KI}, title = {Characteristics of brain lesions found using MRI imaging in patients with post-COVID with signs of cognitive decline.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {77}, number = {3}, pages = {383-386}, doi = {10.36740/WLek202403102}, pmid = {38691776}, issn = {0043-5147}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging/psychology ; *Magnetic Resonance Imaging ; Female ; Male ; *Cognitive Dysfunction/diagnostic imaging/etiology ; Middle Aged ; *Brain/diagnostic imaging/pathology ; SARS-CoV-2 ; Aged ; Adult ; }, abstract = {OBJECTIVE: Aim: To describe and evaluate abnormalities of the brain in post-COVID patients with neurologic symptoms and cognitive deficits using MRI imaging of the brain.

PATIENTS AND METHODS: Materials and Methods: We included 21 patients with a previous positive PCR testing for SARS-CoV-2 and one or more of the following symptoms: memory and cognitive decline, dizziness, anxiety, depression, chronic headaches. All patients had MRI imaging done at onset of symptoms, but after at least 1 year after positive testing for COVID-19 based on the patient's previous medical history.

RESULTS: Results: All of the patients complained of lack of concentration, forgetfulness, hard to process information. 15 patients suffered from confusion, 10 from anxiety. Of the 21 patients 14 had isolated chronic headaches, 3 had isolated dizziness, 4 patients had both symptoms upon inclusion. All patients underwent MRI imaging as a part of the diagnostic workup and had varying degrees of neurodegeneration.

CONCLUSION: Conclusions: Our data correlates with existing research and shows tendency for cognitive decline in post-COVID patients. This provides groundwork for further research to determine correlation between acceleration of neurodegeneration and post-COVID.}, } @article {pmid38690892, year = {2024}, author = {Bramante, CT and Beckman, KB and Mehta, T and Karger, AB and Odde, DJ and Tignanelli, CJ and Buse, JB and Johnson, DM and Watson, RHB and Daniel, JJ and Liebovitz, DM and Nicklas, JM and Cohen, K and Puskarich, MA and Belani, HK and Siegel, LK and Klatt, NR and Anderson, B and Hartman, KM and Rao, V and Hagen, AA and Patel, B and Fenno, SL and Avula, N and Reddy, NV and Erickson, SM and Fricton, RD and Lee, S and Griffiths, G and Pullen, MF and Thompson, JL and Sherwood, NE and Murray, TA and Rose, MR and Boulware, DR and Huling, JD and , }, title = {Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {79}, number = {2}, pages = {354-363}, pmid = {38690892}, issn = {1537-6591}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; K23 DK124654-01-A1/NH/NIH HHS/United States ; OT2HL156812//National Heart, Lung, and Blood Institute of the NIH/ ; UL1 TR002494/TR/NCATS NIH HHS/United States ; //Institute for Engineering in Medicine/ ; //Minnesota's Rainwater Foundation Grant/ ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; //Fast Grants/ ; K23 HL133604/HL/NHLBI NIH HHS/United States ; //Olive View-/ ; //Edenbridge Pharmacy/ ; //Education and Research Institute/ ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; OT2HL161847//NIH RECOVER/ ; //National Cancer Institute of the NIH/ ; //Subaward of the University/ ; //Rainwater Charitable Foundation/ ; T32HL129956//National Heart, Lung, and Blood Institute of the NIH/ ; //Leidos Biomedical/ ; //Apotex Pharmacy/ ; 00086722//Minnesota Partnership for Biotechnology and Medical Genomics/ ; KL2TR002492//UnitedHealth Group Foundation/ ; //Parsemus Foundation/ ; R21 LM012744/LM/NLM NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Metformin/therapeutic use/pharmacology ; *Viral Load/drug effects ; Male ; *SARS-CoV-2/drug effects ; Female ; Middle Aged ; Double-Blind Method ; *COVID-19 Drug Treatment ; *Antiviral Agents/therapeutic use/pharmacology ; Adult ; *COVID-19/virology ; Ivermectin/therapeutic use/pharmacology ; Fluvoxamine/therapeutic use/pharmacology ; Aged ; }, abstract = {BACKGROUND: Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%.

METHODS: COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction.

RESULTS: The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo.

CONCLUSIONS: In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology.

CLINICAL TRIALS REGISTRATION: NCT04510194.}, } @article {pmid38690504, year = {2024}, author = {Amir-Kabirian, B and Annie, FH and Koontz, M and Ihle, R}, title = {Sinus Tachycardia Following COVID-19 and Its Implications.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e57320}, pmid = {38690504}, issn = {2168-8184}, abstract = {Background Within the cardiovascular system, sinus tachycardia has been a noted finding in patients with post-COVID-19 syndrome (symptoms persisting beyond 12 weeks post-infection). To better understand post-COVID-19 tachycardia, we examined the prevalence of sinus tachycardia 12-16 weeks after diagnosis of SARS-COV-2 infection and its correlation with intensive care utilization, ventilator use, and mortality in vaccinated and unvaccinated patients. Methods We identified adult patients in the TriNetX COVID-19 Research Network with confirmed SARS-COV-2 diagnosis from January 20th, 2020, to February 14th, 2022, and sinus tachycardia 12-16 weeks after diagnosis. Two cohorts were created: patients who developed tachycardia 12 weeks after initial diagnosis and patients without tachycardia. The tachycardia cohort was divided further based on vaccination status. Results Of 1,363,907 patients included, 30,705 (2.2%) developed tachycardia. The patients with tachycardia had more comorbidities. Using propensity score matching (PSM), two cohorts of 30,702 were created. The SARS-COV-2 tachycardic cohort had higher mortality (5.1% vs 2.1%, p<0.001), critical care utilization (5.8% vs 2.2%, p<0.001), and ventilator use (1.8% vs 0.5%, p<0.001). Out of 22,878 patients with persistent tachycardia and recorded vaccination status, 14,840 (65%) were not vaccinated. Mortality (5.9% vs 2.3%, p<0.001), critical care utilization (8.3% vs 3.6%, p<0.001), and ventilator use (3.8% vs 0.6%, p<0.001) were higher in the non-vaccinated patients compared with the vaccinated patients after PSM. Conclusion The prevalence of persistent tachycardia after SARS-COV-2 infection is notable at 2.2%. Patients with persistent tachycardia have higher mortality rates and demonstrate greater healthcare utilization at one year compared to patients without persistent tachycardia, particularly if unvaccinated.}, } @article {pmid38690133, year = {2024}, author = {Sun, K and Zhou, R and Xu, F and Lu, H and Asakawa, T}, title = {Proposal to apply a "Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA)" based approach to manage the COVID-19-related mental health problems in the era of long COVID.}, journal = {Global health & medicine}, volume = {6}, number = {2}, pages = {160-163}, pmid = {38690133}, issn = {2434-9194}, abstract = {Long COVID (LC)-related health problems are highly concerned. Many patients seem to have "recovered" from an acute SARS-CoV-2 infection, however, they might experience various symptoms, almost involving all organs and systems. Of those, neuropsychiatric symptoms like depression, anxiety, and post-traumatic stress disorder (PTSD) are not rare. These problems significantly impact the quality of life (QOL) of patients, family, and caregivers, even lead a tragic suicide outcome. Other than the conventional psychological and medical approaches, here, we proposal a positive emotion, engagement, relationships, meaning, and accomplishment (PERMA)-based approach to fight against these COVID-19-related mental health problems (CRMHPs). This approach is characterized by positive psychological interventions and self-achievements, which has been proved to be a powerful tool against mood disorders in common people. Nowadays, abolishment of certain prophylactic measures (such as isolation, lockdown, compulsorily wearing a mask and maintaining social distance, measures to avoid crowding) enables us to have more opportunities to contact patients and implement the PERMA-based approach to the patients with CRMHPs. We believe that application of PERMA-based approach is conducive to alleviate the influence of the CRMHPs and improve their QOL.}, } @article {pmid38689605, year = {2024}, author = {Carlile, O and Briggs, A and Henderson, AD and Butler-Cole, BFC and Tazare, J and Tomlinson, LA and Marks, M and Jit, M and Lin, LY and Bates, C and Parry, J and Bacon, SCJ and Dillingham, I and Dennison, WA and Costello, RE and Walker, AJ and Hulme, W and Goldacre, B and Mehrkar, A and MacKenna, B and , and Herrett, E and Eggo, RM}, title = {Impact of long COVID on health-related quality-of-life: an OpenSAFELY population cohort study using patient-reported outcome measures (OpenPROMPT).}, journal = {The Lancet regional health. Europe}, volume = {40}, number = {}, pages = {100908}, pmid = {38689605}, issn = {2666-7762}, abstract = {BACKGROUND: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems.

METHODS: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID.

FINDINGS: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72-5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37-30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss.

INTERPRETATION: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease.

FUNDING: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).}, } @article {pmid38688088, year = {2024}, author = {Kaplan, K and Mendenhall, E}, title = {Framing Long Covid through Patient activism in the United States: Patient, Provider, Academic, and Policymaker Views.}, journal = {Social science & medicine (1982)}, volume = {350}, number = {}, pages = {116901}, doi = {10.1016/j.socscimed.2024.116901}, pmid = {38688088}, issn = {1873-5347}, mesh = {Humans ; United States ; *COVID-19/psychology/epidemiology ; Male ; Female ; *Qualitative Research ; Post-Acute COVID-19 Syndrome ; Middle Aged ; Social Media ; Adult ; SARS-CoV-2 ; Patient Advocacy ; Interviews as Topic ; Aged ; }, abstract = {In 2020, when COVID-19 patients first recognized their complex and progressive symptoms, patient activists defined "Long Covid" on social media. While patient support groups are by no means new, the predominance of online support groups and those leveraging the power of social media has become a defining characteristic of Long Covid. In this article, we argue that naming Long Covid served as a powerful conduit of legitimacy for patient activists in media, medicine, and policy. We conducted 57 in-depth qualitative interviews with patients (n = 22), clinicians (n = 20), and policy and academic experts (n = 15). We found naming was not a primary area of contention. In contrast, patients found pride and a sense of identity within the terms. Many clinicians struggled with diagnostics because Long Covid lacks clear biological tests, while patients were consistently disappointed by the lack of positive tests and clarity around their symptomatology. The heterogeneity of the Long Covid experience, as well as the diversity of symptoms, further provides opportunities for contestation and disbelief among clinicians and policymakers not only in diagnostics but also in disability rights. Thus, the power of patient activism has transformed how the condition is perceived among and between patients, clinicians, policymakers, and the media in unprecedented ways that will likely have longstanding impacts on how IACCs are viewed in medicine and the public alike.}, } @article {pmid38687984, year = {2024}, author = {Resendez, S and Brown, SH and Ruiz Ayala, HS and Rangan, P and Nebeker, J and Montella, D and Elkin, PL}, title = {Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease: Population-Based Case-Crossover Study.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e49841}, pmid = {38687984}, issn = {2369-2960}, support = {R21 AA026954/AA/NIAAA NIH HHS/United States ; R25 LM014213/LM/NLM NIH HHS/United States ; T15 LM012495/LM/NLM NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Risk Factors ; Male ; *Post-Acute COVID-19 Syndrome ; Female ; *Cross-Over Studies ; Middle Aged ; United States/epidemiology ; Aged ; International Classification of Diseases ; Adult ; }, abstract = {BACKGROUND: There have been over 772 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID (post-COVID-19 condition) and its attendant morbidities and costs. Numerous life-altering complications have already been associated with the development of long COVID, including chronic fatigue, brain fog, and dangerous heart rhythms.

OBJECTIVE: We aim to derive an actionable long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support pandemic-related clinical, public health, research, and policy initiatives.

METHODS: This research employs a case-crossover population-based study using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) data generated at Veterans Affairs medical centers nationwide between January 1, 2020, and August 18, 2022. In total, 367,148 individuals with ICD-10-CM data both before and after a positive COVID-19 test were selected for analysis. We compared ICD-10-CM codes assigned 1 to 7 months following each patient's positive test with those assigned up to 6 months prior. Further, 350,315 patients had novel codes assigned during this window of time. We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of ≥1:1000, and they significantly increased in our entire cohort after a positive test. We present odds ratios with CIs for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based on a patient's demographics, Elixhauser score, vaccination status, and COVID-19 disease severity.

RESULTS: We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID-19 population. We defined 17 medical-specialty long COVID subtypes such as cardiology long COVID. Patients who were COVID-19-positive developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (268,320/449,450, based on a denominator of all patients who were COVID-19-positive). The long COVID cohort was 8 years older with more comorbidities (2-year Elixhauser score 7.97 in the patients with long COVID vs 4.21 in the patients with non-long COVID). Patients who had a more severe bout of COVID-19, as judged by their minimum oxygen saturation level, were also more likely to develop long COVID.

CONCLUSIONS: An actionable, data-driven definition of long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. This long COVID definition can also support public health, research, and policy initiatives. Patients with COVID-19 who are older or have low oxygen saturation levels during their bout of COVID-19, or those who have multiple comorbidities should be preferentially watched for the development of long COVID.}, } @article {pmid38686827, year = {2024}, author = {Blitshteyn, S and Verduzco-Gutierrez, M}, title = {Long COVID: A Major Public Health Issue.}, journal = {American journal of physical medicine & rehabilitation}, volume = {103}, number = {9}, pages = {e131-e132}, doi = {10.1097/PHM.0000000000002486}, pmid = {38686827}, issn = {1537-7385}, mesh = {Humans ; *COVID-19/epidemiology ; *Public Health ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid38684843, year = {2024}, author = {Delgado-Alonso, C and Delgado-Alvarez, A and Díez-Cirarda, M and Oliver-Mas, S and Cuevas, C and Montero-Escribano, P and Ramos-Leví, AM and Gil-Moreno, MJ and López-Carbonero, JI and Hermann, BP and Matias-Guiu, J and Matias-Guiu, JA}, title = {Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9806}, pmid = {38684843}, issn = {2045-2322}, support = {INT20/00079//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; INT23/00017//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CD22/00043//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; }, mesh = {Humans ; *Multiple Sclerosis/complications/psychology ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; *COVID-19/complications/psychology/virology ; *Fatigue ; *Neuropsychological Tests ; *Cognition ; *Cognitive Dysfunction ; Depression ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/isolation & purification ; }, abstract = {Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.}, } @article {pmid38684819, year = {2024}, author = {Jansen, EB and Ostadgavahi, AT and Hewins, B and Buchanan, R and Thivierge, BM and Sganzerla Martinez, G and Goncin, U and Francis, ME and Swan, CL and Scruten, E and Bell, J and Darbellay, J and Facciuolo, A and Falzarano, D and Gerdts, V and Fenton, ME and Hedlin, P and Kelvin, DJ and Kelvin, AA}, title = {PASC (Post Acute Sequelae of COVID-19) is associated with decreased neutralizing antibody titers in both biological sexes and increased ANG-2 and GM-CSF in females.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9854}, pmid = {38684819}, issn = {2045-2322}, support = {GA2-177714//Canadian Institutes for Health Research/ ; 6425//Saskatchewan Health Research Foundation/ ; }, mesh = {Humans ; *COVID-19/immunology/blood/virology ; Female ; *Antibodies, Neutralizing/blood/immunology ; Male ; Middle Aged ; *SARS-CoV-2/immunology/isolation & purification ; *Granulocyte-Macrophage Colony-Stimulating Factor/immunology/blood ; Adult ; *Antibodies, Viral/blood/immunology ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Aged ; Sex Factors ; Angiotensin-Converting Enzyme 2/metabolism ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) or the continuation of COVID-19 (Coronavirus disease 2019) symptoms past 12 weeks may affect as many as 30% of people recovering from a SARS-CoV-2 (severe acute respiratory coronavirus 2) infection. The mechanisms regulating the development of PASC are currently not known; however, hypotheses include virus reservoirs, pre-existing conditions, microblood clots, immune dysregulation, as well as poor antibody responses. Importantly, virus neutralizing antibodies are essential for COVID-19 recovery and protection from reinfection but there is currently limited information on these immune regulators and associated cytokines in PASC patients. Understanding the key drivers of general and specific symptoms associated with Long COVID and the presence of virus neutralizing antibodies in PASC will aid in the development of therapeutics, diagnostics, and vaccines which currently do not exist. We designed a cross-sectional study to investigate systemic antibody and cytokine responses during COVID-19 recovery and PASC. In total, 195 participants were recruited in one of four groups: (1) Those who never had COVID-19 (No COVID); (2) Those in acute COVID-19 recovery (Acute Recovery) (4-12 weeks post infection); (3) Those who recovered from COVID-19 (Recovered) (+ 12 weeks from infection); and (4) those who had PASC (PASC) (+ 12 weeks from infection). Participants completed a questionnaire on health history, sex, gender, demographics, experiences with COVID-19 acute and COVID-19 recovery/continuing symptoms. Serum samples collected were evaluated for antibody binding to viral proteins, virus neutralizing antibody titers, and serum cytokine levels using Ella SimplePlex Immunoassay™ panels. We found participants with PASC reported more pre-existing conditions (e.g. such as hypertension, asthma, and obesity), and PASC symptoms (e.g. fatigue, brain fog, headaches, and shortness of breath) following COVID-19 than COVID-19 Recovered individuals. Importantly, we found PASC individuals to have significantly decreased levels of neutralizing antibodies toward both SARS-CoV-2 and the Omicron BA.1 variant. Sex analysis indicated that female PASC study participants had sustained antibody levels as well as levels of the inflammatory cytokines GM-CSF and ANG-2 over time following COVID-19. Our study reports people experiencing PASC had lower levels of virus neutralizing antibodies; however, the results are limited by the collection time post-COVID-19 and post-vaccination. Moreover, we found females experiencing PASC had sustained levels of GM-CSF and ANG-2. With lower levels of virus neutralizing antibodies, this data suggests that PASC individuals not only have had a suboptimal antibody response during acute SARS-CoV-2 infection but may also have increased susceptibility to subsequent infections which may exacerbate or prolong current PASC illnesses. We also provide evidence suggesting GM-CSF and ANG-2 to play a role in the sex-bias of PASC. Taken together, our findings maybe important for understanding immune molecular drivers of PASC and PASC subgroups.}, } @article {pmid38684388, year = {2024}, author = {Slankamenac, J and Ranisavljev, M and Todorovic, N and Ostojic, J and Stajer, V and Candow, DG and Ratgeber, L and Betlehem, J and Acs, P and Ostojic, SM}, title = {Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.}, journal = {Journal of nutritional science and vitaminology}, volume = {70}, number = {2}, pages = {174-178}, doi = {10.3177/jnsv.70.174}, pmid = {38684388}, issn = {1881-7742}, mesh = {Humans ; *Creatine/administration & dosage ; Male ; Female ; Double-Blind Method ; *Dietary Supplements ; Adult ; *Glucose/administration & dosage ; Middle Aged ; *COVID-19/complications ; SARS-CoV-2 ; Fatigue/drug therapy ; Post-Acute COVID-19 Syndrome ; Brain/drug effects/metabolism ; Treatment Outcome ; }, abstract = {Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η[2]=0.72; left paracentral grey matter F=19.243, p=0.019; partial η[2]=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.}, } @article {pmid38683740, year = {2024}, author = {}, title = {Corrections to: COVID-19 and the Postviral Syndrome of Long COVID: Where We Have Come from and Where We Are Going.}, journal = {Health & social work}, volume = {49}, number = {2}, pages = {e1}, doi = {10.1093/hsw/hlae010}, pmid = {38683740}, issn = {1545-6854}, } @article {pmid38681774, year = {2023}, author = {Salihoğlu, R and Saraçoğlu, F and Sibai, M and Zengin, T and Abak Masud, B and Karasoy, O and Süzek, T}, title = {CompCorona: A web application for comparative transcriptome analyses of coronaviruses reveals SARS-CoV-2-specific host response.}, journal = {Turkish journal of biology = Turk biyoloji dergisi}, volume = {47}, number = {6}, pages = {393-405}, pmid = {38681774}, issn = {1303-6092}, abstract = {BACKGROUND/AIM: Understanding the mechanism of host transcriptomic response to infection by the SARS-CoV-2 virus is crucial, especially for patients suffering from long-term effects of COVID-19, such as long COVID or pericarditis inflammation, potentially linked to side effects of the SARS-CoV-2 spike proteins. We conducted comprehensive transcriptome and enrichment analyses on lung and peripheral blood mononuclear cells (PBMCs) infected with SARS-CoV-2, as well as on SARS-CoV and MERS-CoV, to uncover shared pathways and elucidate their common disease progression and viral replication mechanisms.

MATERIALS AND METHODS: We developed CompCorona, the first interactive online tool for visualizing gene response variance among the family Coronaviridae through 2D and 3D principal component analysis (PCA) and exploring systems biology variance using pathway plots. We also made preprocessed datasets of lungs and PBMCs infected by SARS-CoV-2, SARS-CoV, and MERS-CoV publicly available through CompCorona.

RESULTS: One remarkable finding from the lung and PBMC datasets for infections by SARS-CoV-2, but not infections by other coronaviruses (CoVs), was the significant downregulation of the angiogenin (ANG) and vascular endothelial growth factor A (VEGFA) genes, both directly involved in epithelial and vascular endothelial cell dysfunction. Suppression of the TNF signaling pathway was also observed in cells infected by SARS-CoV-2, along with simultaneous activation of complement and coagulation cascades and pertussis pathways. The ribosome pathway was found to be universally suppressed across all three viruses. The CompCorona online tool enabled the comparative analysis of 9 preprocessed host transcriptome datasets of cells infected by CoVs, revealing the specific host response differences in cases of SARS-CoV-2 infection. This included identifying markers of epithelial dysfunction via interactive 2D and 3D PCA, Venn diagrams, and pathway plots.

CONCLUSION: Our findings suggest that infection by SARS-CoV-2 might induce pulmonary epithelial dysfunction, a phenomenon not observed in cells infected by other CoVs. The publicly available CompCorona tool, along with the preprocessed datasets of cells infected by various CoVs, constitutes a valuable resource for further research into CoV-associated syndromes.}, } @article {pmid38678084, year = {2024}, author = {Gutman, EG and Salvio, AL and Fernandes, RA and Duarte, LA and Raposo-Vedovi, JV and Alcaraz, HF and Teixeira, MA and Passos, GF and de Medeiros, KQM and Hammerle, MB and Pires, KL and Vasconcelos, CCF and Leon, LAA and Figueiredo, CP and Alves-Leon, SV}, title = {Long COVID: plasma levels of neurofilament light chain in mild COVID-19 patients with neurocognitive symptoms.}, journal = {Molecular psychiatry}, volume = {29}, number = {10}, pages = {3106-3116}, pmid = {38678084}, issn = {1476-5578}, support = {E-26/210.254/2020//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro)/ ; E-26/210.657/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro)/ ; E-26/210.273/2018//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro)/ ; E-26/201.040/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro)/ ; E-26/201.406/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro)/ ; VPPCB-005-FIO-20-2-56//Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz (Centro de Pesquisas Aggeu Magalhães, FIOCRUZ)/ ; }, mesh = {Humans ; *COVID-19/blood/complications ; Middle Aged ; Male ; Female ; *Neurofilament Proteins/blood ; Adult ; *Cognitive Dysfunction/blood/etiology ; *Biomarkers/blood ; *SARS-CoV-2 ; Neuropsychological Tests ; Adolescent ; Young Adult ; Post-Acute COVID-19 Syndrome ; Fatigue/blood/etiology ; }, abstract = {It is well known the potential of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection to induce post-acute sequelae, a condition called Long COVID. This syndrome includes several symptoms, but the central nervous system (CNS) main one is neurocognitive dysfunction. Recently it has been demonstrated the relevance of plasma levels of neurofilament light chain (pNfL), as a biomarker of early involvement of the CNS in COVID-19. The aim of this study was to investigate the relationship between pNfL in patients with post-acute neurocognitive symptoms and the potential of NfL as a prognostic biomarker in these cases. A group of 63 long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the long COVID assessment and used for measurement of pNfL with the Single molecule array (SIMOA) assays. Levels of pNfL were significantly higher in long COVID patients with neurocognitive symptoms when compared to HC (p = 0.0031). Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive lost and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively). Previous reports suggested that pNfL levels are related with higher risk of severity and predict lethality of COVID-19. Our findings demonstrate that SARS-CoV-2 infection seems to have a long-term impact on the brain, even in patients who presented mild acute disease. NfL measurements might be useful to identify CNS involvement in long COVID associated with neurocognitive symptoms and to identify who will need continuous monitoring and treatment support.}, } @article {pmid38678079, year = {2024}, author = {Tangsathajaroenporn, W and Panumasvivat, J and Wangsan, K and Muangkaew, S and Kiratipaisarl, W}, title = {Factors affecting the work ability of nursing personnel with post-COVID infection.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9694}, pmid = {38678079}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Adult ; Retrospective Studies ; Middle Aged ; Surveys and Questionnaires ; SARS-CoV-2/isolation & purification ; Nurses ; }, abstract = {Post-COVID infection have raised concerns regarding their impact on nursing personnel's work ability. This study aimed to assess the relationship between post-COVID infection and work ability among nursing personnel. A retrospective observational study from December 2022 to January 2023 involved 609 nursing personnel with a history of COVID-19 infection at a tertiary hospital. An online questionnaire measured post-COVID infection, personal and working factors, and the Work Ability Index (WAI). Long COVID was defined as the continuation or development of new symptoms 1 month post COVID-19 infection. Of 609 personnel, 586 showed post-COVID symptoms (fatigue, cough, difficulty breathing, etc.), with 73.72% in the short COVID group and 26.28% in the long COVID group. A significant association was found between WAI and post-COVID infection (aOR: 3.64, 95% CI 1.59-8.30), with the short COVID group had a significantly higher WAI than the long COVID group (mean difference 2.25, 95% CI 1.44-3.05). The factors related to work ability in the long COVID group were chronic diseases, work limitation, low job control (P < 0.05). Post-COVID infection, especially long COVID, adversely affect nursing personnel's work ability. Enhancing job control and addressing work limitations are crucial for supporting their return to work.}, } @article {pmid38675974, year = {2024}, author = {Antia, A and Alvarado, DM and Zeng, Q and Casorla-Perez, LA and Davis, DL and Sonnek, NM and Ciorba, MA and Ding, S}, title = {SARS-CoV-2 Omicron BA.1 Variant Infection of Human Colon Epithelial Cells.}, journal = {Viruses}, volume = {16}, number = {4}, pages = {}, pmid = {38675974}, issn = {1999-4915}, support = {F30 AI181285/AI/NIAID NIH HHS/United States ; T32 DK007130/DK/NIDDK NIH HHS/United States ; R01 AI150796/AI/NIAID NIH HHS/United States ; R01 DK109384/DK/NIDDK NIH HHS/United States ; U19 AI116484/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; R01 AI167285/AI/NIAID NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2/genetics/physiology/pathogenicity ; *Colon/virology ; *COVID-19/virology ; *Epithelial Cells/virology ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; Virus Replication ; Interferon Lambda ; }, abstract = {The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms.}, } @article {pmid38675914, year = {2024}, author = {Nunes, JM and Kell, DB and Pretorius, E}, title = {Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Viruses}, volume = {16}, number = {4}, pages = {}, pmid = {38675914}, issn = {1999-4915}, support = {142142//National Research Foundation/ ; NNF10CC1016517//Novo Nordisk Foundation/ ; }, mesh = {Humans ; *Endothelial Cells/virology ; *Fatigue Syndrome, Chronic/virology/physiopathology ; Herpesviridae/physiology ; *Herpesviridae Infections/virology ; Virus Latency ; Post-Acute COVID-19 Syndrome/pathology/physiopathology ; }, abstract = {Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.}, } @article {pmid38675888, year = {2024}, author = {Thümmler, L and Beckmann, N and Sehl, C and Soddemann, M and Braß, P and Bormann, M and Brochhagen, L and Elsner, C and Hoertel, N and Cougoule, C and Ciesek, S and Widera, M and Dittmer, U and Lindemann, M and Horn, PA and Witzke, O and Kadow, S and Kamler, M and Gulbins, E and Becker, KA and Krawczyk, A}, title = {Fluoxetine and Sertraline Potently Neutralize the Replication of Distinct SARS-CoV-2 Variants.}, journal = {Viruses}, volume = {16}, number = {4}, pages = {}, pmid = {38675888}, issn = {1999-4915}, mesh = {*SARS-CoV-2/drug effects ; *Sertraline/pharmacology ; *Fluoxetine/pharmacology ; *Virus Replication/drug effects ; Humans ; *Antiviral Agents/pharmacology ; Chlorocebus aethiops ; Vero Cells ; *COVID-19/virology ; Animals ; COVID-19 Drug Treatment ; }, abstract = {The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.}, } @article {pmid38675423, year = {2024}, author = {Noce, A and Marrone, G and Di Lauro, M and Vita, C and Montalto, G and Giorgino, G and Chiaramonte, C and D'Agostini, C and Bernardini, S and Pieri, M}, title = {Potential Anti-Inflammatory and Anti-Fatigue Effects of an Oral Food Supplement in Long COVID Patients.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {4}, pages = {}, pmid = {38675423}, issn = {1424-8247}, abstract = {Long coronavirus disease (COVID) syndrome leads to chronic inflammatory state onset that can have a multisystem impact and compromise organ function. Moreover, long COVID syndrome is often characterized by the presence of chronic fatigue, which affects subjects' daily activities and worsens their quality of life. The aim of our double-blind, placebo-controlled randomized trial (protocol code RS 150.21, approved on 4 November 2021) was to evaluate the beneficial effects of the consumption of 2 cps/day, for two months, of an oral food supplement (OFS), based on Echinacea angustifolia, rosehip, propolis, royal jelly and zinc, in long COVID patients, compared to a two-month placebo period. The OFS's vitamin C content was equal to 22.17 mg/g (8.87 mg/capsule). The OFS's total polyphenol content was 43.98 mg/g gallic acid equivalents. At the end of the in vivo study, we highlighted a significant decrease in the inflammatory parameters in the OFS period, compared to the placebo period (neutrophil-to-lymphocyte ratio, p = 0.0455; monocyte to-lymphocyte ratio, p = 0.0005; C-reactive protein, p = 0.0145). Our study also highlighted a significant increase in vitamin D serum values (p = 0.0005) and, at the same time, an improvement in patients' life quality and a reduction in fatigue, monitored by the fatigue severity scale. This study showed the OFS's beneficial effects on the inflammatory state, fatigue and quality of life in long COVID patients.}, } @article {pmid38674588, year = {2024}, author = {Brogna, C and Bisaccia, DR and Costanzo, V and Lettieri, G and Montano, L and Viduto, V and Fabrowski, M and Cristoni, S and Prisco, M and Piscopo, M}, title = {Who Is the Intermediate Host of RNA Viruses? A Study Focusing on SARS-CoV-2 and Poliovirus.}, journal = {Microorganisms}, volume = {12}, number = {4}, pages = {}, pmid = {38674588}, issn = {2076-2607}, abstract = {The COVID-19 pandemic has sparked a surge in research on microbiology and virology, shedding light on overlooked aspects such as the infection of bacteria by RNA virions in the animal microbiome. Studies reveal a decrease in beneficial gut bacteria during COVID-19, indicating a significant interaction between SARS-CoV-2 and the human microbiome. However, determining the origins of the virus remains complex, with observed phenomena such as species jumps adding layers to the narrative. Prokaryotic cells play a crucial role in the disease's pathogenesis and transmission. Analyzing previous studies highlights intricate interactions from clinical manifestations to the use of the nitrogen isotope test. Drawing parallels with the history of the Poliovirus underscores the need to prioritize investigations into prokaryotic cells hosting RNA viruses.}, } @article {pmid38674318, year = {2024}, author = {Mujovic, N and Nikolic, D and Markovic, F and Stjepanovic, M and Zekovic, M and Ali, HSH and Zivanovic, D and Savic, M and Laban, M}, title = {The Effects of Six Weeks Pulmonary Rehabilitation on Functional and Psychological Outcomes in Long-COVID Patients: Preliminary Results from Serbian Single Center Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {4}, pages = {}, pmid = {38674318}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/rehabilitation/psychology ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; SARS-CoV-2 ; Treatment Outcome ; Walk Test ; Anxiety ; Adult ; }, abstract = {Background and Objectives: In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients. Material and Methods: The prospective clinical study included 46 patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO2, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot. Results: On discharge, in comparison with admission, the values of SpO2 were significantly lower (p = 0.007) before the 6MWT, and VAS scores were significantly higher (p = 0.036), while after the 6MWT, VAS scores were significantly lower (p < 0.001) as were Borg scores (p = 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (p = 0.005) before the StS test, and Borg scores were significantly lower (p = 0.001), while after the StS test, SpO2 levels were significantly higher (p = 0.036) and VAS scores were significantly lower (p < 0.001), as were Borg scores (p = 0.008). After discharge, the values of the StS test were significantly higher (p = 0.011), PHQ9 scores were significantly lower (p < 0.001) and GAD anxiety scores were significantly lower as well (p = 0.005), while the distances measured in meters on the 6MWT were significantly increased (p < 0.001). Conclusions: A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.}, } @article {pmid38673548, year = {2024}, author = {Blitshteyn, S and Lange, A and Corinaldi, C and Guy, P and Brook, J}, title = {Sexual Dysfunction in Postural Orthostatic Tachycardia Syndrome (POTS): A Cross-Sectional, Case-Control Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {8}, pages = {}, pmid = {38673548}, issn = {2077-0383}, support = {xx//Dysautonomia Information Network (DINET)/ ; }, abstract = {Background: We aimed to determine whether patients with postural orthostatic tachycardia syndrome (POTS) have sexual dysfunction compared to age-matched healthy controls. Methods: Utilizing online COMPASS-31 to evaluate dysautonomia symptom severity, Beck's Depression Inventory Second Edition (BDII), Female Sexual Function (FSF), and International Index of Erection Function (IIEF) questionnaires, we compared sexual function scores in patients with POTS to scores obtained from sex- and age-matched healthy controls via a cross-sectional case-control study. Results: A total of 160 women with POTS, mean age 30.2 ± 7.9 (range 21-50 years), had lower FSF scores than 62 healthy age-matched female controls. IIEF scores in 29 male patients with POTS with a mean age of 30.1 ± 6.0 (range 21-47) were significantly lower than in 27 healthy age-matched male controls. Female POTS patients had significantly lower scores in the sub-domains of desire, arousal, and satisfaction, while male POTS patients had significantly lower scores in erectile and orgasmic function, desire, and satisfaction than healthy controls. Predictive factors of sexual dysfunction were depression in women and age in men. The severity of autonomic symptoms correlated with sexual dysfunction in women, but this effect disappeared after controlling for depression. Conclusions: Compared to healthy controls, women and men with POTS have significant sexual dysfunction, which needs to be considered in the diagnostic and therapeutic approaches as part of comprehensive patient care.}, } @article {pmid38673514, year = {2024}, author = {Wiśniewska, A and Kijak, A and Nowak, K and Lulek, M and Skwarek, A and Małecka-Giełdowska, M and Śmiarowski, M and Wąsik, S and Ciepiela, O}, title = {Organ-Dysfunction Markers in Mild-to-Moderate COVID-19 Convalescents.}, journal = {Journal of clinical medicine}, volume = {13}, number = {8}, pages = {}, pmid = {38673514}, issn = {2077-0383}, abstract = {Background: A coronavirus disease 2019 (COVID-19) outbreak led to a worldwide pandemic. COVID-19 not only caused acute symptoms during the severe phase of the disease, but also induced long-term side effects on the functioning of many organs and systems. Symptoms that were associated with the disease and present at least 3 months after recovery were named long COVID. The aim of this study was to assess if mild-to-moderate COVID-19 may lead to the dysfunction of respiratory, cardiovascular, neural, and renal systems in healthy blood donors who recovered from the disease at least 6 months earlier. Methods: Here, we examined 294 adults among volunteer blood donors divided into convalescents (n = 215) and healthy controls (n = 79). Concentrations of soluble CD163, TGF beta, Lp-PLA2, NCAM-1, S100, NGAL, and creatinine were measured either by ELISA or automated methods. The probability value p < 0.05 was considered as statistically significant. Results: We found significant differences in Lp-PLA2, S100, and NCAM-1 between convalescents and never-infected subjects. Lp-PLA2 and NCAM-1 were lower, and S100 higher, in convalescents than in the control group. Conclusion: Mild-to-moderate COVID-19 convalescents are at a low risk of developing lung fibrosis or chronic kidney disease. However, they should regularly carry out their prophylaxis examinations for early detection of possible negative outcomes of COVID-19.}, } @article {pmid38673384, year = {2024}, author = {Diar Bakerly, N and Smith, N and Darbyshire, JL and Kwon, J and Bullock, E and Baley, S and Sivan, M and Delaney, B}, title = {Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {4}, pages = {}, pmid = {38673384}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets.

METHODS: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools.

RESULTS: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors.

CONCLUSIONS: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A 'treatable trait' approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.}, } @article {pmid38672973, year = {2024}, author = {Ferous, S and Siafakas, N and Boufidou, F and Patrinos, GP and Tsakris, A and Anastassopoulou, C}, title = {Investigating ABO Blood Groups and Secretor Status in Relation to SARS-CoV-2 Infection and COVID-19 Severity.}, journal = {Journal of personalized medicine}, volume = {14}, number = {4}, pages = {}, pmid = {38672973}, issn = {2075-4426}, abstract = {The ABO blood groups, Lewis antigens, and secretor systems are important components of transfusion medicine. These interconnected systems have been also shown to be associated with differing susceptibility to bacterial and viral infections, likely as the result of selection over the course of evolution and the constant tug of war between humans and infectious microbes. This comprehensive narrative review aimed to explore the literature and to present the current state of knowledge on reported associations of the ABO, Lewis, and secretor blood groups with SARS-CoV-2 infection and COVID-19 severity. Our main finding was that the A blood group may be associated with increased susceptibility to SARS-CoV-2 infection, and possibly also with increased disease severity and overall mortality. The proposed pathophysiological pathways explaining this potential association include antibody-mediated mechanisms and increased thrombotic risk amongst blood group A individuals, in addition to altered inflammatory cytokine expression profiles. Preliminary evidence does not support the association between ABO blood groups and COVID-19 vaccine response, or the risk of developing long COVID. Even though the emergency state of the pandemic is over, further research is needed especially in this area since tens of millions of people worldwide suffer from lingering COVID-19 symptoms.}, } @article {pmid38672710, year = {2024}, author = {Wu, BQ and Liu, DY and Shen, TC and Lai, YR and Yu, TL and Hsu, HL and Lee, HM and Liao, WC and Hsia, TC}, title = {Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {38672710}, issn = {2075-1729}, abstract = {The coronavirus disease (COVID-19) pandemic has resulted in an increasing population that is experiencing a wide range of long-lasting symptoms after recovery from the acute infection. Long COVID refers to this specific condition and is associated with diverse symptoms, such as fatigue, myalgias, dyspnea, headache, cognitive impairment, neurodegenerative symptoms, anxiety, depression, and a sense of despair. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. We conducted a literature search between 1 January 2019 and 30 October 2023, focusing on the clinical efficacy and utility of HBOT for treating long COVID and found ten clinical studies that fit the review topic, including one case report, five one-group pretest-posttest design studies, one safety report from a randomized controlled trial (RCT), and three complete reports of RCTs. Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations.}, } @article {pmid38672267, year = {2024}, author = {Golzardi, M and Hromić-Jahjefendić, A and Šutković, J and Aydin, O and Ünal-Aydın, P and Bećirević, T and Redwan, EM and Rubio-Casillas, A and Uversky, VN}, title = {The Aftermath of COVID-19: Exploring the Long-Term Effects on Organ Systems.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672267}, issn = {2227-9059}, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalised. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection.

RESULTS: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC.

CONCLUSIONS: Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed.}, } @article {pmid38672245, year = {2024}, author = {Kell, DB and Lip, GYH and Pretorius, E}, title = {Fibrinaloid Microclots and Atrial Fibrillation.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672245}, issn = {2227-9059}, abstract = {Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known 'risk factors' for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.}, } @article {pmid38672208, year = {2024}, author = {Casal-Guisande, M and Comesaña-Campos, A and Núñez-Fernández, M and Torres-Durán, M and Fernández-Villar, A}, title = {Proposal and Definition of an Intelligent Clinical Decision Support System Applied to the Prediction of Dyspnea after 12 Months of an Acute Episode of COVID-19.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672208}, issn = {2227-9059}, abstract = {Long COVID is a condition that affects a significant proportion of patients who have had COVID-19. It is characterised by the persistence of associated symptoms after the acute phase of the illness has subsided. Although several studies have investigated the risk factors associated with long COVID, identifying which patients will experience long-term symptoms remains a complex task. Among the various symptoms, dyspnea is one of the most prominent due to its close association with the respiratory nature of COVID-19 and its disabling consequences. This work proposes a new intelligent clinical decision support system to predict dyspnea 12 months after a severe episode of COVID-19 based on the SeguiCovid database from the Álvaro Cunqueiro Hospital in Vigo (Galicia, Spain). The database is initially processed using a CART-type decision tree to identify the variables with the highest predictive power. Based on these variables, a cascade of expert systems has been defined with Mamdani-type fuzzy-inference engines. The rules for each system were generated using the Wang-Mendel automatic rule generation algorithm. At the output of the cascade, a risk indicator is obtained, which allows for the categorisation of patients into two groups: those with dyspnea and those without dyspnea at 12 months. This simplifies follow-up and the performance of studies aimed at those patients at risk. The system has produced satisfactory results in initial tests, supported by an AUC of 0.75, demonstrating the potential and usefulness of this tool in clinical practice.}, } @article {pmid38672194, year = {2024}, author = {Urbiola-Salvador, V and Lima de Souza, S and Macur, K and Czaplewska, P and Chen, Z}, title = {Plasma Proteomics Elucidated a Protein Signature in COVID-19 Patients with Comorbidities and Early-Diagnosis Biomarkers.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672194}, issn = {2227-9059}, support = {decision numbers 325965, 335579//Research Council of Finland/ ; }, abstract = {Despite great scientific efforts, deep understanding of coronavirus-19 disease (COVID-19) immunopathology and clinical biomarkers remains a challenge. Pre-existing comorbidities increase the mortality rate and aggravate the exacerbated immune response against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which can result in more severe symptoms as well as long-COVID and post-COVID complications. In this study, we applied proteomics analysis of plasma samples from 28 patients with SARS-CoV-2, with and without pre-existing comorbidities, as well as their corresponding controls to determine the systemic protein changes caused by the SARS-CoV-2 infection. As a result, the protein signature shared amongst COVID-19 patients with comorbidities was revealed to be characterized by alterations in the coagulation and complement pathways, acute-phase response proteins, tissue damage and remodeling, as well as cholesterol metabolism. These altered proteins may play a relevant role in COVID-19 pathophysiology. Moreover, several novel potential biomarkers for early diagnosis of the SARS-CoV-2 infection were detected, such as increased levels of keratin K22E, extracellular matrix protein-1 (ECM1), and acute-phase response protein α-2-antiplasmin (A2AP). Importantly, elevated A2AP may contribute to persistent clotting complications associated with the long-COVID syndrome in patients with comorbidities. This study provides new insights into COVID-19 pathogenesis and proposes novel potential biomarkers for early diagnosis that could be facilitated for clinical application by further validation studies.}, } @article {pmid38672163, year = {2024}, author = {Maniaci, A and Lavalle, S and Masiello, E and Lechien, JR and Vaira, L and Boscolo-Rizzo, P and Musa, M and Gagliano, C and Zeppieri, M}, title = {Platelet-Rich Plasma (PRP) in the Treatment of Long COVID Olfactory Disorders: A Comprehensive Review.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672163}, issn = {2227-9059}, abstract = {Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual's quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort.}, } @article {pmid38671529, year = {2024}, author = {de Pádua Serafim, A and Saffi, F and Soares, ARA and Morita, AM and Assed, MM and de Toledo, S and Rocca, CCA and Durães, RSS}, title = {Cognitive performance of post-covid patients in mild, moderate, and severe clinical situations.}, journal = {BMC psychology}, volume = {12}, number = {1}, pages = {236}, pmid = {38671529}, issn = {2050-7283}, support = {2020/07957-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Cognition ; Severity of Illness Index ; Aged ; Attention ; Cognitive Dysfunction/psychology ; SARS-CoV-2 ; Depression/psychology ; Anxiety/psychology ; Neuropsychological Tests ; }, abstract = {BACKGROUND: Studying individuals with varying symptoms, from mild to severe, can provide valuable insights into the spectrum of cognitive outcomes after COVID-19. We investigated the cognitive performance of adults who recovered from the novel coronavirus disease (COVID-19) without prior cognitive complaints, considering mild (not hospitalized), moderate (ward), and severe (intensive care unit) symptoms.

METHODS: This cross-sectional study included 302 patients who recovered from COVID-19 (mild, n = 102; moderate, n = 102; severe, n = 98). We assessed intellectual quotient (IQ), attention, memory, processing speed, visual-constructive ability, as well as symptoms of depression, anxiety, and stress, at least eighteen months after infection. The mean length of hospitalization was Mdays=8.2 (SD = 3.9) and Mdays=14.4 (SD = 8.2) in the moderate and severe groups, respectively.

RESULTS: Cognitive difficulties were present in all three groups: mild (n = 12, 11.7%), moderate (n = 40, 39.2%), and severe (n = 48, 48.9%). Using Multinomial Logistic Regression and considering the odds ratio, our results indicated that a one-point increase in sustained attention, visual memory, and working memory might decrease the odds of being categorized in the severe group by 20%, 24%, and 77%, respectively, compared to the mild group.

CONCLUSIONS: Our findings provide empirical evidence regarding the long-term cognitive effects of COVID-19, particularly in individuals experiencing severe manifestations of the disease. We also highlighted the need for a comprehensive, multidimensional approach in rehabilitation programs to address the enduring cognitive impacts of COVID-19.}, } @article {pmid38671455, year = {2024}, author = {Ghasemiyeh, P and Mohammadi-Samani, S}, title = {Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development.}, journal = {Virology journal}, volume = {21}, number = {1}, pages = {98}, pmid = {38671455}, issn = {1743-422X}, mesh = {Humans ; *COVID-19/prevention & control/immunology ; *COVID-19 Vaccines/immunology/adverse effects/administration & dosage ; *SARS-CoV-2/immunology ; *Vaccine Development ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; Post-Acute COVID-19 Syndrome ; Drug Repositioning ; }, abstract = {About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.}, } @article {pmid38670844, year = {2024}, author = {Xie, Z and Stallings-Smith, S and Patel, S and Case, S and Hong, YR}, title = {COVID-19 booster vaccine uptake and reduced risks for long-COVID: A cross-sectional study of a U.S. adult population.}, journal = {Vaccine}, volume = {42}, number = {16}, pages = {3529-3535}, doi = {10.1016/j.vaccine.2024.04.070}, pmid = {38670844}, issn = {1873-2518}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology ; Adult ; Male ; Cross-Sectional Studies ; Female ; *Immunization, Secondary/statistics & numerical data ; Middle Aged ; United States/epidemiology ; *COVID-19 Vaccines/administration & dosage/immunology ; Young Adult ; *SARS-CoV-2/immunology ; Aged ; Adolescent ; Post-Acute COVID-19 Syndrome ; Prevalence ; }, abstract = {Long-COVID (having symptoms lasting 3 months or longer post-infection) is an emerging public health concern, yet research on whether COVID-19 booster vaccines can mitigate this condition is limited. This study examined associations between booster uptake and long-COVID prevalence among U.S. adults. Data were analyzed from 8757 adults aged 18 years or older with a history of COVID-19 infection from the 2022 National Health Interview Survey. Weighted prevalence and logistic regression models examined relationships between self-reported COVID-19 booster vaccination status and long-COVID, adjusting for sociodemographics and health factors. 19.5 % reported experiencing long-COVID. Individuals receiving the COVID-19 booster vaccine had significantly lower adjusted odds of long-COVID (OR 0.75, 95 % CI 0.61-0.93) compared to unvaccinated individuals. Overall, these findings suggest that COVID-19 booster vaccination is associated with a reduced prevalence of long-COVID among the U.S. adult population, underscoring the importance of optimizing booster uptake to mitigate the long-term impacts of COVID-19.}, } @article {pmid38670520, year = {2024}, author = {Velásquez García, HA and Wong, S and Jeong, D and Binka, M and Naveed, Z and Wilton, J and Hawkins, NM and Janjua, NZ}, title = {Risk of Major Adverse Cardiovascular Events After SARS-CoV-2 Infection in British Columbia: A Population-Based Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.010}, pmid = {38670520}, issn = {1555-7162}, abstract = {BACKGROUND: COVID-19 is associated with increased risk of post-acute cardiovascular outcomes. Population-based evidence for long periods of observation is still limited.

METHODS: This population-based cohort study was conducted using data (2020-2021) from the British Columbia COVID-19 Cohort. The exposure of interest was severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified through reverse transcription-polymerase chain reaction (RT-PCR) assay. Individuals who tested positive (exposed) on RT-PCR were matched to negative controls (unexposed) on sex, age, and RT-PCR collection date in a 1:4 ratio. Outcomes of interest were incident major adverse cardiovascular events and acute myocardial infarction, identified more than 30 days after RT-PCR collection date. The association between SARS-CoV-2 infection and cardiovascular risk was assessed through multivariable survival models. Population attributable fractions were computed from Cox models.

RESULTS: We included 649,320 individuals: 129,864 exposed and 519,456 unexposed. The median duration of follow-up was 260 days; 1,786 events (0.34%) took place among the unexposed, and 702 (0.54%) in the exposed. The risk of major adverse cardiovascular events was higher in the exposed (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI], 1.22-1.46), with greater risk observed in those who were hospitalized (aHR 3.81; 95% CI, 3.12-4.65) or required intensive care unit admission (aHR 6.25; 95% CI, 4.59-8.52) compared with the unexposed group. The fraction of cardiovascular events attributable to SARS-CoV-2 was 7.04% (95% CI, 4.67-9.41%). Comparable results were observed for acute myocardial infarction.

CONCLUSIONS: SARS-CoV-2 infection was associated with higher cardiovascular risk, with graded increase across the acute COVID-19 severity, contributing to 7% of incident major adverse cardiovascular events. These findings suggest that long-term monitoring of cardiovascular risk is required in COVID-19 survivors.}, } @article {pmid38669034, year = {2024}, author = {Bock, A}, title = {Researchers See Hope in Symptom-Guided Exercise for Long COVID With Postexertional Malaise.}, journal = {JAMA}, volume = {331}, number = {19}, pages = {1609-1611}, doi = {10.1001/jama.2024.7255}, pmid = {38669034}, issn = {1538-3598}, mesh = {Humans ; COVID-19/complications/rehabilitation ; *Exercise Therapy/methods ; *Post-Acute COVID-19 Syndrome/epidemiology/etiology/rehabilitation ; Sweden/epidemiology ; United States/epidemiology ; Symptom Flare Up ; }, } @article {pmid38668888, year = {2024}, author = {Molnar, T and Lehoczki, A and Fekete, M and Varnai, R and Zavori, L and Erdo-Bonyar, S and Simon, D and Berki, T and Csecsei, P and Ezer, E}, title = {Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.}, journal = {GeroScience}, volume = {46}, number = {5}, pages = {5267-5286}, pmid = {38668888}, issn = {2509-2723}, mesh = {Humans ; *COVID-19/complications/physiopathology/therapy ; *Post-Acute COVID-19 Syndrome ; *Mitochondria/metabolism ; SARS-CoV-2 ; Oxidative Stress/physiology ; Mitochondrial Diseases/therapy/physiopathology ; }, abstract = {The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition.}, } @article {pmid38668125, year = {2024}, author = {Rudroff, T}, title = {Decoding Post-Viral Fatigue: The Basal Ganglia's Complex Role in Long-COVID.}, journal = {Neurology international}, volume = {16}, number = {2}, pages = {380-393}, pmid = {38668125}, issn = {2035-8385}, abstract = {Long-COVID afflicts millions with relentless fatigue, disrupting daily life. The objective of this narrative review is to synthesize current evidence on the role of the basal ganglia in long-COVID fatigue, discuss potential mechanisms, and highlight promising therapeutic interventions. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases. Mounting evidence from PET, MRI, and functional connectivity data reveals basal ganglia disturbances in long-COVID exhaustion, including inflammation, metabolic disruption, volume changes, and network alterations focused on striatal dopamine circuitry regulating motivation. Theories suggest inflammation-induced signaling disturbances could impede effort/reward valuation, disrupt cortical-subcortical motivational pathways, or diminish excitatory input to arousal centers, attenuating drive initiation. Recent therapeutic pilots targeting basal ganglia abnormalities show provisional efficacy. However, heterogeneous outcomes, inconsistent metrics, and perceived versus objective fatigue discrepancies temper insights. Despite the growing research, gaps remain in understanding the precise pathways linking basal ganglia dysfunction to fatigue and validating treatment efficacy. Further research is needed to advance understanding of the basal ganglia's contribution to long-COVID neurological sequelae and offer hope for improving function across the expanding affected population.}, } @article {pmid38666878, year = {2024}, author = {Paradiso, B and Pauza, DH and Limback, C and Ottaviani, G and Thiene, G}, title = {From Psychostasis to the Discovery of Cardiac Nerves: The Origins of the Modern Cardiac Neuromodulation Concept.}, journal = {Biology}, volume = {13}, number = {4}, pages = {}, pmid = {38666878}, issn = {2079-7737}, abstract = {This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul". The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability", on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations.}, } @article {pmid38664674, year = {2024}, author = {Fang, C and Akhtar Baz, S and Sheard, L and Carpentieri, JD}, title = {Correction: "They seemed to be like cogs working in different directions": a longitudinal qualitative study on long COVID healthcare services in the United Kingdom from a person-centred lens.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {525}, doi = {10.1186/s12913-024-11015-x}, pmid = {38664674}, issn = {1472-6963}, } @article {pmid38664324, year = {2024}, author = {Noij, LCE and Blankestijn, JM and Lap, CR and van Houten, MA and Biesbroek, G and der Zee, AM and Abdel-Aziz, MI and van Goudoever, JB and Alsem, MW and Brackel, CLH and Oostrom, KJ and Hashimoto, S and Terheggen-Lagro, SWJ}, title = {Clinical-based phenotypes in children with pediatric post-COVID-19 condition.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {7}, pages = {682-691}, pmid = {38664324}, issn = {1867-0687}, mesh = {Humans ; Child ; Female ; *COVID-19/epidemiology ; Male ; Adolescent ; *Phenotype ; Child, Preschool ; Netherlands/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Pediatric post coronavirus disease 2019 (COVID-19) condition (PPCC) is a heterogeneous syndrome, which can significantly affect the daily lives of children. This study aimed to identify clinically meaningful phenotypes in children with PPCC, to better characterize and treat this condition.

METHODS: Participants were children with physician-diagnosed PPCC, referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March 2023. Demographic factors and information on post-COVID symptoms, comorbidities, and impact on daily life were collected. Clinical clusters were identified using an unsupervised and unbiased approach for mixed data types.

RESULTS: Analysis of 111 patients (aged 3-18 years) revealed three distinct clusters within PPCC. Cluster 1 (n = 62, median age = 15 years) predominantly consisted of girls (74.2%). These patients suffered relatively more from exercise intolerance, dyspnea, and smell disorders. Cluster 2 (n = 33, median age = 13 years) contained patients with an even gender distribution (51.5% girls). They suffered from relatively more sleep problems, memory loss, gastrointestinal symptoms, and arthralgia. Cluster 3 (n = 16, median age = 11 years) had a higher proportion of boys (75.0%), suffered relatively more from fever, had significantly fewer symptoms (median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively), and experienced a lower impact on daily life.

CONCLUSIONS: This study identified three distinct clinical PPCC phenotypes, with variations in sex, age, symptom patterns, and impact on daily life. These findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children.}, } @article {pmid38664068, year = {2024}, author = {Luedke, JC and Vargas, G and Jashar, DT and Malone, LA and Morrow, A and Ng, R}, title = {Neuropsychological functioning of pediatric patients with long COVID.}, journal = {The Clinical neuropsychologist}, volume = {38}, number = {8}, pages = {1855-1872}, pmid = {38664068}, issn = {1744-4144}, support = {P50 HD103538/HD/NICHD NIH HHS/United States ; U18 HS029920/HS/AHRQ HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Child ; Male ; *Neuropsychological Tests ; Adolescent ; *COVID-19/complications/psychology ; *Executive Function/physiology ; Child, Preschool ; Attention/physiology ; Post-Acute COVID-19 Syndrome ; Young Adult ; Depression/psychology ; Anxiety/psychology ; Cognitive Dysfunction/etiology/physiopathology ; Parents/psychology ; Affect ; }, abstract = {Objective: To determine the neurocognitive profile for youth with long COVID presenting with cognitive concerns. Method: This study is a case series of 54 pediatric patients (65% female, Mage = 13.48, SDage = 3.10, 5-19) with long COVID who were referred for neuropsychological testing from a post-COVID-19 multidisciplinary clinic. The outcomes of interest were neuropsychological test scores and parent ratings of mood, attention, and executive functioning. The percentage of patients with neuropsychological test scores below the 9th percentile (below average range) and those with at-risk or clinically significant scores (T-scores > 59) on parent-informant inventories were computed. Results: A portion of children with long COVID showed weaknesses in sustained attention (29%) and divided attention (35%). This portion of patients did not significantly differ when comparing patients with and without pre-existing attention and mood concerns. A high percentage of parents reported at-risk to clinically significant concerns for cognitive regulation (53%), depression (95%), anxiety (85%), and inattention (66%) on standardized questionnaires. Conclusions: The present case series showed that approximately a third of children with long COVID demonstrate objective weaknesses on sustained and divided attention tasks but were largely intact in other domains of neuropsychological functioning. Importantly, children with long COVID had similar difficulties in attention, regardless of pre-existing attention or mood concerns. Parents reported high rates of mood, anxiety, and executive functioning difficulties which likely impact daily functioning. Attention and emotional regulation should be closely monitored and treated as necessary in pediatric patients with long COVID to aid functional recovery.}, } @article {pmid38663887, year = {2024}, author = {Blankestijn, JM and Abdel-Aziz, MI and Baalbaki, N and Bazdar, S and Beekers, I and Beijers, RJHCG and Bloemsma, LD and Cornelissen, MEB and Gach, D and Houweling, L and Holverda, S and Jacobs, JJL and Jonker, R and van der Lee, I and Linders, PMA and Mohamed Hoesein, FAA and Noij, LCE and Nossent, EJ and van de Pol, MA and Schaminee, DW and Schols, AMWJ and Schuurman, LT and Sondermeijer, B and Geelhoed, JJM and van den Bergh, JP and Weersink, EJM and de Wit-van Wijck, Y and Maitland-van der Zee, AH and , }, title = {Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.}, journal = {BMJ open respiratory research}, volume = {11}, number = {1}, pages = {}, pmid = {38663887}, issn = {2052-4439}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Female ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *Phenotype ; *SARS-CoV-2 ; Aged ; Severity of Illness Index ; Adult ; Cohort Studies ; Respiratory Function Tests ; Cluster Analysis ; Forced Expiratory Volume ; Time Factors ; }, abstract = {BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient.

METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering.

RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category.

CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.}, } @article {pmid38663793, year = {2024}, author = {Sawano, M and Wu, Y and Shah, RM and Zhou, T and Arun, AS and Khosla, P and Kaleem, S and Vashist, A and Bhattacharjee, B and Ding, Q and Lu, Y and Caraballo, C and Warner, F and Huang, C and Herrin, J and Putrino, D and Michelsen, T and Fisher, L and Adinig, C and Iwasaki, A and Krumholz, HM}, title = {Long COVID Characteristics and Experience: A Descriptive Study From the Yale LISTEN Research Cohort.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.015}, pmid = {38663793}, issn = {1555-7162}, abstract = {BACKGROUND: The experience of people with long COVID needs further amplification, especially with a comprehensive focus on symptomatology, treatments, and the impact on daily life and finances. Our intent is to describe the experience of people with long COVID symptomatology and characterize the psychological, social, and financial challenges they experience.

METHODS: We collected data from individuals aged 18 and older reporting long COVID as participants in the Yale Listen to Immune, Symptom and Treatment Experiences Now study. The sample population included 441 participants surveyed between May 2022 and July 2023. We evaluated their demographic characteristics, socioeconomic and psychological status, index infection period, health status, quality of life, symptoms, treatments, prepandemic comorbidities, and new-onset conditions.

RESULTS: Overall, the median age of the participants with long COVID was 46 years (interquartile range [IQR]: 38-57 years); 74% were women, 86% were non-Hispanic White, and 93% were from the United States. Participants reported a low health status measured by the Euro-QoL visual analog scale, with a median score of 49 (IQR: 32-61). Participants documented a diverse range of symptoms, with all 96 possible symptom choices being reported. Additionally, participants had tried many treatments (median number of treatments: 19, IQR: 12-28). They were also experiencing psychological distress, social isolation, and financial stress.

CONCLUSIONS: Despite having tried numerous treatments, participants with long COVID continued to experience an array of health and financial challenges-findings that underscore the failure of the healthcare system to address the medical needs of people with long COVID. These insights highlight the need for crucial medical, mental health, financial, and community support services, as well as further scientific investigation to address the complex impact of long COVID.}, } @article {pmid38663424, year = {2024}, author = {Buonsenso, D and Tantisira, KG}, title = {Long COVID and SARS-CoV-2 persistence: new answers, more questions.}, journal = {The Lancet. Infectious diseases}, volume = {24}, number = {8}, pages = {796-798}, doi = {10.1016/S1473-3099(24)00216-0}, pmid = {38663424}, issn = {1474-4457}, mesh = {Humans ; *COVID-19/epidemiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38663423, year = {2024}, author = {Zuo, W and He, D and Liang, C and Du, S and Hua, Z and Nie, Q and Zhou, X and Yang, M and Tan, H and Xu, J and Yu, Y and Zhan, Y and Zhang, Y and Gu, X and Zhu, W and Zhang, H and Li, H and Sun, W and Sun, M and Liu, X and Liu, L and Cao, C and Li, R and Li, J and Zhang, Y and Zhang, Y and Guo, J and Zhao, L and Zhang, CP and Liu, H and Wang, S and Xiao, F and Wang, Y and Wang, Z and Li, H and Cao, B}, title = {The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China.}, journal = {The Lancet. Infectious diseases}, volume = {24}, number = {8}, pages = {845-855}, doi = {10.1016/S1473-3099(24)00171-3}, pmid = {38663423}, issn = {1474-4457}, mesh = {Humans ; *COVID-19/epidemiology/diagnosis/virology ; Cross-Sectional Studies ; *SARS-CoV-2/isolation & purification ; Male ; Female ; Middle Aged ; China/epidemiology ; Adult ; Cohort Studies ; Aged ; Lung/virology ; }, abstract = {BACKGROUND: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms.

METHODS: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms.

FINDINGS: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms.

INTERPRETATION: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms.

FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.}, } @article {pmid38662331, year = {2024}, author = {Mendes, D and Machira Krishnan, S and O'Brien, E and Padgett, T and Harrison, C and Strain, WD and Manca, A and Ustianowski, A and Butfield, R and Hamson, E and Reynard, C and Yang, J}, title = {Modelling COVID-19 Vaccination in the UK: Impact of the Autumn 2022 and Spring 2023 Booster Campaigns.}, journal = {Infectious diseases and therapy}, volume = {13}, number = {5}, pages = {1127-1146}, pmid = {38662331}, issn = {2193-8229}, abstract = {INTRODUCTION: The delivery of COVID-19 vaccines was successful in reducing hospitalizations and mortality. However, emergence of the Omicron variant resulted in increased virus transmissibility. Consequently, booster vaccination programs were initiated to decrease the risk of severe disease and death among vulnerable members of the population. This study aimed to estimate the effects of the booster program and alternative vaccination strategies on morbidity and mortality due to COVID-19 in the UK.

METHOD: A Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to assess the impact of several vaccination strategies on severe outcomes associated with COVID-19, including hospitalizations, mortality, National Health Service (NHS) capacity quantified by hospital general ward and intensive care unit (ICU) bed days, and patient productivity. The model accounted for age-, risk- and immunity-based stratification of the UK population. Outcomes were evaluated over a 48-week time horizon from September 2022 to August 2023 considering the actual UK autumn 2022/spring 2023 booster campaigns and six counterfactual strategies.

RESULTS: The model estimated that the autumn 2022/spring 2023 booster campaign resulted in a reduction of 18,921 hospitalizations and 1463 deaths, compared with a no booster scenario. Utilization of hospital bed days due to COVID-19 decreased after the autumn 2022/spring 2023 booster campaign. Expanding the booster eligibility criteria and improving uptake improved all outcomes, including averting twice as many ICU admissions, preventing more than 20% additional deaths, and a sevenfold reduction in long COVID, compared with the autumn 2022/spring 2023 booster campaign. The number of productive days lost was reduced by fivefold indicating that vaccinating a wider population has a beneficial impact on the morbidities associated with COVID-19.

CONCLUSION: Our modelling demonstrates that the autumn 2022/spring 2023 booster campaign reduced COVID-19-associated morbidity and mortality. Booster campaigns with alternative eligibility criteria warrant consideration in the UK, given their potential to further reduce morbidity and mortality as future variants emerge.}, } @article {pmid38661341, year = {2024}, author = {Reay, A and Dismore, L and Aujayeb, A and Dotchin, C and Tullo, E and Steer, J and Swainston, K}, title = {Analysing the patient experience of COVID-19: Exploring patients' experiences of hospitalisation and their quality of life post discharge.}, journal = {Journal of clinical nursing}, volume = {33}, number = {9}, pages = {3634-3641}, doi = {10.1111/jocn.17194}, pmid = {38661341}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Quality of Life/psychology ; Male ; *Patient Discharge ; Female ; Middle Aged ; *Hospitalization ; *Qualitative Research ; Aged ; SARS-CoV-2 ; Adult ; }, abstract = {AIMS AND OBJECTIVES: We sought to gain an understanding of the patient experience during their hospital stay for COVID-19, and the impact of COVID-19 on quality of life post discharge.

BACKGROUND: Symptoms of COVID-19 include a persistent cough, dyspnoea and fatigue. Individuals with comorbidities such as cardiovascular disease have a higher risk of contracting COVID-19 and approximately 20% of those diagnosed with COVID-19 are admitted to hospital. Following discharge from hospital, 40% of patients report a worsened quality of life and up to 87% of those discharged from hospital have experienced 'long COVID'.

DESIGN: A qualitative design was used to understand patient experience of hospitalisation following a diagnosis of COVID-19, and their experiences following discharge from hospital.

METHODS: Ten patients with a previous diagnosis of COVID-19 took part in semi-structured interviews regarding their experiences of hospitalisation and the impact on quality of life post-discharge.

RESULTS: The results identified three key themes from the interviews: communication and the inpatient experience, symptoms following discharge and regaining independence. Patients discussed their experience of hospitalisation and how this continued to impact their emotional well-being post-discharge. However, patients appeared to push themselves physically to improve their health, despite continued COVID-19 symptoms.

CONCLUSION: Patients hospitalised following a diagnosis of COVID-19 experienced psychological distress during their hospital stay, as well as 3-months post-discharge. We suggest the use of psychosocial interventions to support patients post-discharge.

The results of this study provide a greater understanding of the patient experience during their hospital stay, which can support nursing staff practice. Additionally, the study provides in depth knowledge of personal experiences of patients diagnosed with COVID-19 and the impact following hospital discharge.

Patient's took part in semi-structured interviews via telephone to support the aims and objectives of this study.}, } @article {pmid38659602, year = {2024}, author = {Metelkina-Fernandez, V and Dumas, LE and Vandersteen, C and Chirio, D and Gros, A and Fernandez, A and Askenazy, F and Manera, V}, title = {Psychiatric outcomes in outpatients affected by long COVID: A link between mental health and persistence of olfactory complaint.}, journal = {World journal of psychiatry}, volume = {14}, number = {4}, pages = {507-512}, pmid = {38659602}, issn = {2220-3206}, abstract = {BACKGROUND: Anosmia was one of the main symptoms of coronavirus disease 2019 (COVID-19). A psychiatric history (i.e., depression) may be an independent contributor to the risk of COVID-19 diagnosis, and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae (bidirectional association).

AIM: To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory complaints.

METHODS: We conducted a prospective case control study from March 2020 to May 2021. Patients recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint (visual analogue scale) for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by serology. Post-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology department. Psychiatric medical histories were collected by a psychiatrist during the assessments.

RESULTS: Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the study. Fifty percent of the patients were female (n = 17). The group's mean age was 40.5 ± 12.9 years. The control group included 32 participants, of which 34.4% were female (n = 11), and had a mean age of 61.2 ± 12.2 years. The rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher (41.7%) than among patients without (18.8%) (χ[2] = 5.9, P = 0.015).

CONCLUSION: The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent anosmia. It therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk patients. Further prospective, translational, and collaborative studies are needed to extrapolate these results to the general population.}, } @article {pmid38658821, year = {2024}, author = {Benny, D and Giacobini, M and Costa, G and Gnavi, R and Ricceri, F}, title = {Multimorbidity in middle-aged women and COVID-19: binary data clustering for unsupervised binning of rare multimorbidity features and predictive modeling.}, journal = {BMC medical research methodology}, volume = {24}, number = {1}, pages = {95}, pmid = {38658821}, issn = {1471-2288}, mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Multimorbidity ; Middle Aged ; Italy/epidemiology ; Cluster Analysis ; *SARS-CoV-2 ; Severity of Illness Index ; Hospitalization/statistics & numerical data ; Quality of Life ; Cohort Studies ; Machine Learning ; }, abstract = {BACKGROUND: Multimorbidity is typically associated with deficient health-related quality of life in mid-life, and the likelihood of developing multimorbidity in women is elevated. We address the issue of data sparsity in non-prevalent features by clustering the binary data of various rare medical conditions in a cohort of middle-aged women. This study aims to enhance understanding of how multimorbidity affects COVID-19 severity by clustering rare medical conditions and combining them with prevalent features for predictive modeling. The insights gained can guide the development of targeted interventions and improved management strategies for individuals with multiple health conditions.

METHODS: The study focuses on a cohort of 4477 female patients, (aged 45-60) in Piedmont, Italy, and utilizes their multimorbidity data prior to the COVID-19 pandemic from their medical history from 2015 to 2019. The COVID-19 severity is determined by the hospitalization status of the patients from February to May 2020. Each patient profile in the dataset is depicted as a binary vector, where each feature denotes the presence or absence of a specific multimorbidity condition. By clustering the sparse medical data, newly engineered features are generated as a bin of features, and they are combined with the prevalent features for COVID-19 severity predictive modeling.

RESULTS: From sparse data consisting of 174 input features, we have created a low-dimensional feature matrix of 17 features. Machine Learning algorithms are applied to the reduced sparsity-free data to predict the Covid-19 hospital admission outcome. The performance obtained for the corresponding models are as follows: Logistic Regression (accuracy 0.72, AUC 0.77, F1-score 0.69), Linear Discriminant Analysis (accuracy 0.7, AUC 0.77, F1-score 0.67), and Ada Boost (accuracy 0.7, AUC 0.77, F1-score 0.68).

CONCLUSION: Mapping higher-dimensional data to a low-dimensional space can result in information loss, but reducing sparsity can be beneficial for Machine Learning modeling due to improved predictive ability. In this study, we addressed the issue of data sparsity in electronic health records and created a model that incorporates both prevalent and rare medical conditions, leading to more accurate and effective predictive modeling. The identification of complex associations between multimorbidity and the severity of COVID-19 highlights potential areas of focus for future research, including long COVID and intervention efforts.}, } @article {pmid38658496, year = {2024}, author = {Gloeckl, R and Zwick, RH and Fürlinger, U and Schneeberger, T and Leitl, D and Jarosch, I and Behrends, U and Scheibenbogen, C and Koczulla, AR}, title = {Practical Recommendations for Exercise Training in Patients with Long COVID with or without Post-exertional Malaise: A Best Practice Proposal.}, journal = {Sports medicine - open}, volume = {10}, number = {1}, pages = {47}, pmid = {38658496}, issn = {2199-1170}, abstract = {People with long COVID may suffer from a wide range of ongoing symptoms including fatigue, exertional dyspnea, reduced exercise performance, and others. In particular, impaired exercise performance is a condition that can be recovered in many people through an individualized physical exercise training program. However, clinical experience has shown that the presence of post-exertional malaise (PEM) is a significant barrier to physical exercise training in people with long COVID. Currently, there is no guideline or consensus available on how to apply exercise training in this cohort. Therefore, we conducted a literature review in the PubMed library using the following search terms: "COVID", "post-COVID", "long COVID" and "exercise" searching for studies from January 2020 to January 2024. Data from 46 trials were included. Exercise training regimes were very heterogeneous and none of these studies reported on the management of PEM in the context of an exercise training program. Based on the feedback from an additional survey that was answered by 14 international experts in the field of exercise training in long COVID, combined with the authors´ own extensive practical experience, a best practice proposal for exercise training recommendations has been developed. This proposal differentiates exercise procedures according to the presence of no, mild/moderate or severe PEM in people with long COVID. These recommendations may guide allied healthcare professionals worldwide in initiating and adjusting exercise training programs for people with long COVID, stratified according to the presence and severity of PEM.}, } @article {pmid38657605, year = {2024}, author = {Su, Q and Lau, RI and Liu, Q and Li, MKT and Yan Mak, JW and Lu, W and Lau, ISF and Lau, LHS and Yeung, GTY and Cheung, CP and Tang, W and Liu, C and Ching, JYL and Cheong, PK and Chan, FKL and Ng, SC}, title = {The gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome.}, journal = {Cell host & microbe}, volume = {32}, number = {5}, pages = {651-660.e4}, doi = {10.1016/j.chom.2024.04.005}, pmid = {38657605}, issn = {1934-6069}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/microbiology ; *Post-Acute COVID-19 Syndrome ; Male ; *Phenotype ; Female ; *Machine Learning ; *SARS-CoV-2 ; Middle Aged ; Adult ; Bacteria/classification/isolation & purification/genetics ; Aged ; Feces/microbiology/virology ; Cohort Studies ; Longitudinal Studies ; }, abstract = {The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.}, } @article {pmid38657468, year = {2024}, author = {Rusu, EC and Monfort-Lanzas, P and Bertran, L and Barrientos-Riosalido, A and Solé, E and Mahmoudian, R and Aguilar, C and Briansó, S and Mohamed, F and Garcia, S and Camaron, J and Auguet, T}, title = {Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights.}, journal = {Computers in biology and medicine}, volume = {175}, number = {}, pages = {108507}, doi = {10.1016/j.compbiomed.2024.108507}, pmid = {38657468}, issn = {1879-0534}, mesh = {Humans ; *COVID-19/genetics ; *Transcriptome/genetics ; Male ; Female ; *SARS-CoV-2/genetics ; Sex Factors ; Post-Acute COVID-19 Syndrome ; Gene Expression Profiling ; }, abstract = {BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC.

METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns.

KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions.

CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.}, } @article {pmid38657236, year = {2024}, author = {Wang, D and Li, P and Huang, X and Liu, Y and Mao, S and Yin, H and Wang, N and Luo, Y and Sun, S}, title = {Exploring the Prevalence of Tinnitus and Ear-Related Symptoms in China After the COVID-19 Pandemic: Online Cross-Sectional Survey.}, journal = {JMIR formative research}, volume = {8}, number = {}, pages = {e54326}, pmid = {38657236}, issn = {2561-326X}, abstract = {BACKGROUND: Tinnitus is a complex and heterogeneous disease that has been identified as a common manifestation of COVID-19. To gain a comprehensive understanding of tinnitus symptoms in individuals following COVID-19 infection, we conducted an online survey called the China Ear Nose and Throat Symptom Survey in the COVID-19 Pandemic (CENTSS) among the Chinese population.

OBJECTIVE: Our objective was to investigate tinnitus and ear-related symptoms after COVID-19 infection in the Chinese population, with the aim of providing a solid empirical foundation for improved health care. The findings from CENTSS can contribute to the development of enhanced management strategies for tinnitus in the context of long COVID. By gaining a better understanding of the factors contributing to tinnitus in individuals with COVID-19, health care providers can tailor interventions to address the specific needs of affected patients. Furthermore, this study serves as a basis for research on the long-term consequences of COVID-19 infection and its associated tinnitus symptoms.

METHODS: A quantitative, online, cross-sectional survey study design was used to explore the impact of the COVID-19 pandemic on experiences with tinnitus in China. Data were collected through an online questionnaire designed to identify the presence of tinnitus and its impacts. Descriptive statistics were used to analyze individuals' demographic characteristics, COVID-19 infection-related ear symptoms, and the cognitive and emotional implications of tinnitus. Univariable and multivariable logistic regression analyses were used to model the cross-sectional baseline associations between demographic characteristics, noise exposure, educational level, health and lifestyle factors, and the occurrence of tinnitus.

RESULTS: Between December 19, 2022, and February 1, 2023, we obtained responses from 1262 Chinese participants representing 24 regions, with an average age of 37 years. Among them, 540 patients (42.8%) reported experiencing ear-related symptoms after COVID-19 infection. Only 114 (9%) of these patients sought medical attention specifically for their ear symptoms, while 426 (33.8%) did not seek hospital care. Tinnitus emerged as the most prevalent and impactful symptom among all ear-related symptoms experienced after COVID-19 infection. Of the respondents, female participants (688/888, 77.78%), younger individuals (<30 years), individuals with lower education levels, participants residing in western China, and those with a history of otolaryngology diseases were more likely to develop tinnitus following COVID-19 infection.

CONCLUSIONS: In summary, tinnitus was identified as the most common ear-related symptom during COVID-19 infection. Individuals experiencing tinnitus after COVID-19 infection were found to have poorer cognitive and emotional well-being. Different ear-related symptoms in patients post-COVID-19 infection may suggest viral invasion of various parts of the ear. It is therefore crucial to monitor and manage hearing-related changes resulting from COVID-19 as clinical services resume.}, } @article {pmid38657151, year = {2024}, author = {García-Dobarganes-Barlow, FE and Valadez-Soto, JM and Saavedra-Islas, N and García-Romo, VM and Mata-Coronado, J and Villavicencio-Ocampo, E and Encalada-Díaz, MI}, title = {[Avascular necrosis of the hip secondary to long-standing COVID].}, journal = {Acta ortopedica mexicana}, volume = {38}, number = {1}, pages = {48-51}, pmid = {38657151}, issn = {2306-4102}, mesh = {Humans ; Male ; *COVID-19/complications ; Adult ; *Femur Head Necrosis/etiology/surgery ; Time Factors ; Arthroplasty, Replacement, Hip ; Glucocorticoids/therapeutic use/administration & dosage ; }, abstract = {Long COVID is a term used to describe the long-terms effects of COVID-19 infection that continue for weeks or months after the patient has recovered from COVID-19. Long COVID is defined by the persistence of symptoms beyond 12 weeks from the onset of the disease. Corticosteroids are part of the treatment in this period with good results in controlling the disease; however, it is a predisposing factor for the development of avascular necrosis. We present a clinic case of a young man of 39 years old with diagnosis of avascular necrosis in his left hip, before the administration of corticosteroids for the treatment of COVID-19. There is a lack of consensus about the dosage and duration of steroids required to develop avascular necrosis. Some authors have reported that cumulative dose of 2,000 mg prednisone (or its equivalent) was required for avascular necrosis development. For patients with advanced avascular necrosis stages total hip arthroplasty is an attractive option with excellent outcomes in terms of pain relief and survivorship.}, } @article {pmid38656671, year = {2024}, author = {Li, H and Zhao, J and Xing, Y and Chen, J and Wen, Z and Ma, R and Han, F and Huang, B and Wang, H and Li, C and Chen, Y and Ning, X}, title = {Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients Using Machine Learning and Immune Cell Infiltration Analysis.}, journal = {Biochemical genetics}, volume = {}, number = {}, pages = {}, pmid = {38656671}, issn = {1573-4927}, support = {No. 2021E010//Health Research Project of Shaanxi Province/ ; No. 82270715//National Natural Science Foundation of China/ ; No.2023-ZDLSF-15//Key Research and Development Program of Shaanxi Province/ ; }, abstract = {Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.}, } @article {pmid38656063, year = {2024}, author = {Martins, WRM and Cardoso, TV and Oliveira, AL and Fernandes, GS and Fontes, IFL and Dantas, JG and Miranda, JS and Martins, JE and Antunes, LN and Leite, TG}, title = {Long COVID-19 and mnemonic effects: an integrative literature review.}, journal = {Revista da Associacao Medica Brasileira (1992)}, volume = {70}, number = {5}, pages = {e20231211}, pmid = {38656063}, issn = {1806-9282}, mesh = {Humans ; *COVID-19/prevention & control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid38655026, year = {2024}, author = {Gutfreund, MC and Kobayashi, T and Callado, GY and Pardo, I and Hsieh, MK and Lin, V and Perencevich, EN and Salinas, JL and Edmond, MB and Mendonça, E and Rizzo, LV and Marra, AR}, title = {The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: a systematic literature review and meta-analysis.}, journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE}, volume = {4}, number = {1}, pages = {e54}, pmid = {38655026}, issn = {2732-494X}, abstract = {OBJECTIVE: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) in the pediatric population.

DESIGN: Systematic literature review/meta-analysis.

METHODS: We searched PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to August 14, 2023, for studies evaluating the COVID-19 vaccine effectiveness against post-COVID conditions among vaccinated individuals < 21 years old who received at least 1 dose of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present 4 or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% CI) for post-COVID conditions between vaccinated and unvaccinated individuals.

RESULTS: Eight studies with 23,995 individuals evaluated the effect of vaccination on post-COVID conditions, of which 5 observational studies were included in the meta-analysis. The prevalence of children who did not receive COVID-19 vaccines ranged from 65% to 97%. The pooled prevalence of post-COVID conditions was 21.3% among those unvaccinated and 20.3% among those vaccinated at least once. The pooled DOR for post-COVID conditions among individuals vaccinated with at least 1 dose and those vaccinated with 2 doses were 1.07 (95% CI, 0.77-1.49) and 0.82 (95% CI, 0.63-1.08), respectively.

CONCLUSIONS: A significant proportion of children and adolescents were unvaccinated, and the prevalence of post-COVID conditions was higher than reported in adults. While vaccination did not appear protective, conclusions were limited by the lack of randomized trials and selection bias inherent in observational studies.}, } @article {pmid38654678, year = {2024}, author = {Wei, J and Lu, C and Ding, Y and Lu, Y and Yang, X and Zhang, X and Tang, G}, title = {Gustatory dysfunction and long COVID in Chinese patients with COVID-19: A 6-month follow-up study.}, journal = {Oral diseases}, volume = {30}, number = {8}, pages = {5397-5407}, doi = {10.1111/odi.14958}, pmid = {38654678}, issn = {1601-0825}, support = {SHSMU-ZLCX20212401//Innovative Research Team of High-level Local University in Shanghai/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology ; *COVID-19/complications ; Cross-Sectional Studies ; East Asian People ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Risk Factors ; *Taste Disorders/etiology ; }, abstract = {AIMS: To evaluate long COVID of gustatory dysfunction and the associated risk factors regarding onset and recovery in Chinese patients.

METHODS: We conducted a cross-sectional study of patients with SARS-CoV-2 Omicron infection at Changxing Mobile Cabin Hospital in Shanghai, China, from March to May 2022. A prospective follow-up of patients with gustatory dysfunction was conducted at 6 months after discharge.

RESULTS: In total, 18.48% (241/1304) reported gustatory dysfunction. The 6-month follow-up response rate was 89.63% (216/241) and 74.02% recovered their taste sense within 1-3 weeks. A total of 20.37% of patients (44/216) presented with long COVID. Symptoms persisted for 12 patients (5.56%) after 6 months. Having multiple taste impairments (OR, 2.364; 95% CI, 1.286-4.348; p = 0.006) was associated with a higher risk of gustatory dysfunction with long COVID. Having received a COVID-19 vaccine booster was positively associated with taste sensation recovery (HR, 1.344; 95% CI, 1.012-1.785; p = 0.041).

CONCLUSIONS: About 20.37% of patients with COVID-19 might develop long COVID of gustatory dysfunction and 5.56% with persisting changes in their sense of taste. Most patients recovered taste sensations within 1-3 weeks after COVID-19 symptom onset and receiving a booster shot of the COVID-19 vaccine presented a protective effect on the taste sensation recovery.}, } @article {pmid38652733, year = {2024}, author = {Wolf, FI and Trapani, V}, title = {Magnesium and vitamin D in long COVID syndrome; do they help?.}, journal = {Magnesium research}, volume = {0}, number = {0}, pages = {}, doi = {10.1684/mrh.2024.0521}, pmid = {38652733}, issn = {1952-4021}, abstract = {Since the start of the COVID-19 pandemic, it has become increasingly clear that the disease can have relevant multisystemic and long-term effects, and several studies have attempted to identify key determinants of the disease course. Here we discuss recent evidence suggesting that, in long COVID patients, combined magnesium and vitamin D deficiencies associate with a higher number of clinical manifestations, as compared to patients with normal levels of both nutrients. We highlight the potential synergistic effects of these deficiencies and propose that future studies should explore a causal link with the risk of developing long COVID. Most importantly, randomized clinical trials are needed to determine if magnesium and vitamin D supplementation can improve long COVID symptoms, providing a safe and affordable support therapy to the benefit of patients and society.}, } @article {pmid38652535, year = {2024}, author = {Patton, MJ and Benson, D and Robison, SW and Raval, D and Locy, ML and Patel, K and Grumley, S and Levitan, EB and Morris, P and Might, M and Gaggar, A and Erdmann, N}, title = {Characteristics and determinants of pulmonary long COVID.}, journal = {JCI insight}, volume = {9}, number = {10}, pages = {}, pmid = {38652535}, issn = {2379-3708}, support = {K08 AI129705/AI/NIAID NIH HHS/United States ; R01 AI156898/AI/NIAID NIH HHS/United States ; R01 HL149944/HL/NHLBI NIH HHS/United States ; R01 HL153113/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; Retrospective Studies ; *SARS-CoV-2 ; Aged ; *Post-Acute COVID-19 Syndrome ; *Lung/diagnostic imaging/physiopathology ; *Respiratory Function Tests ; Tomography, X-Ray Computed ; Dyspnea/physiopathology/etiology ; Cough/physiopathology ; }, abstract = {BACKGROUNDPersistent cough and dyspnea are prominent features of postacute sequelae of SARS-CoV-2 (also termed "long COVID"); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFT) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary long COVID.METHODSThis single-center retrospective study included 1,097 patients with clinically defined long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for 1 or more months after resolution of primary COVID infection.RESULTSAfter exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified as diffusion impairment and pulmonary restriction, as measured by percentage predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Longitudinal evaluation revealed diffusion impairment (DLCO ≤ 80%) and pulmonary restriction (TLC ≤ 80%) in 51% of the cohort overall (n = 479). In multivariable modeling regression analysis, invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary long COVID with diffusion impairment and restriction (adjusted odds ratio [aOR] = 9.89, 95% CI 3.62-26.9]). Finally, a subanalysis of CT imaging identified radiographic evidence of fibrosis in this patient population.CONCLUSIONLongitudinal PFTs revealed persistent diffusion-impaired restriction as a key feature of pulmonary long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of long COVID patients with prolonged pulmonary symptoms. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary long COVID patients.FUNDINGNational Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund at the University of Alabama at Birmingham.}, } @article {pmid38652515, year = {2024}, author = {Garrett, C and Aghaei, A and Aggarwal, A and Qiao, S}, title = {The Role of Social Media in the Experiences of COVID-19 Among Long-Hauler Women: Qualitative Study.}, journal = {JMIR human factors}, volume = {11}, number = {}, pages = {e50443}, pmid = {38652515}, issn = {2292-9495}, support = {R01 AI127203/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *COVID-19/epidemiology/psychology ; *Qualitative Research ; *Social Media ; Social Support ; Post-Acute COVID-19 Syndrome/epidemiology/psychology ; }, abstract = {BACKGROUND: The extant literature suggests that women are more vulnerable to COVID-19 infection and at higher risk for developing long COVID. Due to pandemic mitigation recommendations, social media was relied upon for various aspects of daily life, likely with differences of usage between genders.

OBJECTIVE: This study aimed to explore the role and functions of social media in the lives of long-hauler women.

METHODS: Participants were purposively snowball-sampled from an online health promotion intervention for long-hauler women with COVID-19 from March to June 2021. During this time, one-on-one, semistructured interviews were conducted online until data saturation was agreed to have been achieved (ie, 15 interviews). Interview transcripts and field notes were analyzed using an emergent, inductive approach.

RESULTS: In total, 15 women were enrolled. The main roles of social media included facilitating support group participation, experience sharing, interpersonal connections, and media consumption. Emergent themes demonstrated that participants rely on social media to fulfill needs of emotional support, social engagement, spirituality, health planning, information gathering, professional support, and recreationally for relaxation. As long-hauler women turn to social media to discuss symptom and health management as well as the intention to vaccinate, this study demonstrates both the associated benefits (ie, decreased isolation) and challenges (ie, misinformation, rumination, resentment, jealousy).

CONCLUSIONS: The public health implications of these findings support the development of gender-tailored health promotion interventions that leverage the benefits of social media, while mitigating the negative impacts, for women with long COVID.}, } @article {pmid38652364, year = {2024}, author = {Jasiczek, J and Doroszko, A and Trocha, T and Trocha, M}, title = {Role of the RAAS in mediating the pathophysiology of COVID-19.}, journal = {Pharmacological reports : PR}, volume = {76}, number = {3}, pages = {475-486}, pmid = {38652364}, issn = {2299-5684}, mesh = {Humans ; *Renin-Angiotensin System/physiology ; *COVID-19/physiopathology/metabolism ; *Angiotensin-Converting Enzyme 2/metabolism ; SARS-CoV-2 ; Animals ; }, abstract = {The renin-angiotensin-aldosterone system (RAAS) holds a position of paramount importance as enzymatic and endocrine homeostatic regulator concerning the water-electrolyte and acid-base balance. Nevertheless, its intricacy is influenced by the presence of various complementary angiotensins and their specific receptors, thereby modifying the primary RAAS actions. Angiotensin-converting enzyme 2 (ACE2) acts as a surface receptor for SARS-CoV-2, establishing an essential connection between RAAS and COVID-19 infection. Despite the recurring exploration of the RAAS impact on the trajectory of COVID-19 along with the successful resolution of many inquiries, its complete role in the genesis of delayed consequences encompassing long COVID and cardiovascular thrombotic outcomes during the post-COVID phase as well as post-vaccination, remains not fully comprehended. Particularly noteworthy is the involvement of the RAAS in the molecular mechanisms underpinning procoagulant processes throughout COVID-19. These processes significantly contribute to the pathogenesis of organ complications as well as determine clinical outcomes and are discussed in this manuscript.}, } @article {pmid38651133, year = {2024}, author = {Staub, K and Ballouz, T and Puhan, M}, title = {An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond).}, journal = {Public health reviews}, volume = {45}, number = {}, pages = {1606966}, pmid = {38651133}, issn = {0301-0422}, abstract = {Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected. Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918-1920 and later. Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years. Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.}, } @article {pmid38649285, year = {2024}, author = {Lelesi, PJ and Bono, L and Gurenlian, JR}, title = {A Protocol for Treating Patients with Post-Covid Conditions in Dental Settings.}, journal = {Journal of dental hygiene : JDH}, volume = {98}, number = {2}, pages = {7-20}, pmid = {38649285}, issn = {1553-0205}, mesh = {Humans ; *COVID-19/complications ; *Dental Hygienists ; *Qualitative Research ; Clinical Protocols ; SARS-CoV-2 ; Female ; Dental Care ; Male ; California ; Adult ; Health Services Accessibility ; Middle Aged ; }, abstract = {Purpose The relative newness of Post-COVID Conditions (PCC) has revealed a void in assessment protocols and treatment guidelines for dental settings. Providing oral health care practitioners with an assessment and treatment protocol could facilitate the delivery of comprehensive oral health care. The purpose of this study was to test a protocol for assessing and treating patients with PCC in dental practice settings.Methods A qualitative exploratory research design was used to conduct the study. A PCC assessment and treatment protocol (ATP) was developed and was used by dental hygienists in clinical practice in California for a period of 6 weeks. Following the use of the PCC ATP practitioners were invited to participate in individual interviews. Online individual interviews were comprised of 20 dental hygienists recruited via purposive sampling. Participant anonymity was preserved using pseudonyms. A qualitative analysis software program was used to identify codes and themes. Investigator triangulation, member checks, and saturation were used to validate responses.Results Fifty-six participants completed the six-week PCC ATP and twenty participants took part in the interview session. Four themes were identified: awareness, accessibility, resources, and complications. Within the accessibility theme, subthemes of ease of use and guidance emerged. The complications theme yielded three subthemes: time, clinician hesitation, and patient lack of cooperation.Conclusion This study demonstrated that a PCC ATP created awareness of the varied symptoms of PCC and is a useful resource for clinical practitioners. Providing dental hygienists with a treatment protocol supports efforts to provide person-centered evidence-based care.}, } @article {pmid38649004, year = {2024}, author = {Shah, KM and Shah, RM and Sawano, M and Wu, Y and Bishop, P and Iwasaki, A and Krumholz, HM}, title = {Factors Associated with Long COVID Recovery among US Adults.}, journal = {The American journal of medicine}, volume = {137}, number = {9}, pages = {896-899}, doi = {10.1016/j.amjmed.2024.04.017}, pmid = {38649004}, issn = {1555-7162}, mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age Factors ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Hispanic or Latino ; *Post-Acute COVID-19 Syndrome/epidemiology ; Sex Factors ; United States/epidemiology ; White ; }, abstract = {BACKGROUND: While factors associated with long COVID (LC) continue to be illuminated, little is known about recovery. This study used national survey data to assess factors associated with recovery from LC.

METHODS: We used data from the 2022 National Health Interview Survey, a cross-sectional sample of noninstitutionalized US adults. Survey analysis was used to account for oversampling and nonresponse bias and to obtain nationally representative estimates. A multivariable logistic regression model was used to identify potential predictors of LC recovery.

RESULTS: Among those reporting ever having COVID-19, 17.7% or an estimated 17.5 million American adults reported ever having LC, and among those with LC, 48.5% or an estimated 8.5 million reported having recovered. Multivariable logistic regression analysis showed that Hispanic adults were significantly more likely than White adults to report recovery from LC. At the same time, those with severe COVID-19 symptoms and those who had more than a high school degree, were aged 40 years or older, or were female were less likely to report recovery.

CONCLUSION: Significant variations in LC recovery were noted across age, sex, race and ethnicity, education, and severity of COVID-19 symptoms. Further work is needed to elucidate the causes of these differences and identify strategies to increase recovery rates.}, } @article {pmid38648998, year = {2024}, author = {Palau, P and Calvo, B and Sastre, C and Domínguez, E and Marín, P and Flor, C and Núñez, J and López, L}, title = {Unraveling the Mechanisms Behind Exercise Intolerance and Recovery in Long COVID.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.023}, pmid = {38648998}, issn = {1555-7162}, abstract = {BACKGROUND: Patients suffering from long COVID may exhibit autonomic dysregulation. However, the association between autonomic dysregulation and exercise intolerance and the impact of therapeutic interventions on its modulation remains unclear. This study investigated the relationship between heart rate recovery at the first minute (HRR1), a proxy for autonomic imbalance, and exercise intolerance in patients with long COVID. Additionally, the study aimed to assess the effects of a 12-week home-based inspiratory muscle training program on autonomic modulation in this patient population.

METHODS: This study is a post hoc subanalysis of a randomized trial in which 26 patients with long COVID were randomly assigned to receive either a 12-week inspiratory muscle training program or usual care alone (NCT05279430). The data were analyzed using Pearson's correlation and linear mixed regression analysis.

RESULTS: The mean age was 50.4 ± 12.2 years, and 11 (42.3%) were women. Baseline HRR1 was significantly correlated with maximal functional capacity (peakVO2) (r = 0.402, P = .041). Patients with lower baseline HRR1 (≤22 bpm) exhibited higher resting heart rates and lower peakVO2. Inspiratory muscle training led to a more substantial increase in peakVO2 in patients with lower HRR1 at baseline (P = .019). Additionally, a significant improvement in HRR1 was observed in the IMT group compared to the usual care group after 12-week (Δ +9.39, 95% CI = 2.4-16.4, P = .010).

CONCLUSION: Lower baseline HRR1 is associated with exercise intolerance in long COVID patients and may serve as a valuable criterion for identifying individuals likely to benefit more from a home-based inspiratory muscle training program.}, } @article {pmid38646896, year = {2024}, author = {Sun, C and Liu, Z and Li, S and Wang, Y and Liu, G}, title = {Impact of Long COVID on Health-Related Quality of Life Among Patients After Acute COVID-19 Infection: A Cross-Sectional Study.}, journal = {Inquiry : a journal of medical care organization, provision and financing}, volume = {61}, number = {}, pages = {469580241246461}, pmid = {38646896}, issn = {1945-7243}, mesh = {Humans ; *Quality of Life ; *COVID-19/psychology/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; China/epidemiology ; *SARS-CoV-2 ; Adult ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Propensity Score ; Aged ; }, abstract = {Concerns have been raised globally regarding the long-term effects of the novel coronavirus disease 2019 (COVID-19). This study aimed to investigate the impact of long COVID on the health of patients recovering from acute COVID-19 in China. We conducted a cross-sectional questionnaire survey from 1 February to 9 March 2023. Propensity score matching (PSM) was used to understand the differences in health utility values between individuals with and without long COVID. Factors associated with health-related quality of life (HRQoL) were determined using a multiple linear regression model. A chi-square test was used to compare differences between the 2 groups for each dimension of the EuroQoL-5 Dimension-5 Level (EQ-5D-5L) scale. In total, 307 participants were included in the analysis, of which 40.39% exhibited at least 1 persistent symptom. The common symptoms of long COVID were fatigue/weakness, coughing, memory decline, poor concentration, and phlegm in the throat. Most patients with long COVID reported mild effects from their symptoms. After propensity score matching, the long-COVID group had lower health utility scores than the non-long-COVID group (0.94 vs 0.97). In the multivariable linear regression analysis, persistent symptoms and low annual household income were associated with lower health utility values (P < .05). Anxiety/depression and pain/discomfort were the major problems experienced by the participants with long COVID. Long-COVID symptoms following acute COVID-19 infection have a serious impact on health-related quality of life. Therefore, it is necessary to implement interventions to improve patient health after the recovery from acute COVID-19.}, } @article {pmid38646658, year = {2024}, author = {Fernández-de-Las-Peñas, C and Pellicer-Valero, OJ and Martín-Guerrero, JD and Hernández-Barrera, V and Arendt-Nielsen, L}, title = {Investigating the fluctuating nature of post-COVID pain symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study.}, journal = {Pain reports}, volume = {9}, number = {3}, pages = {e1153}, pmid = {38646658}, issn = {2471-2531}, abstract = {OBJECTIVE: This cohort study used Sankey plots and exponential bar plots for visualizing the fluctuating nature and trajectory of post-COVID pain in previously hospitalized COVID-19 survivors.

METHODS: A cohort of 1266 subjects hospitalised because of COVID-19 during the first wave of the pandemic were scheduled for a telephone interview at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months in average after hospitalization for collecting data about post-COVID pain. Patients were asked for about pain symptomatology that was attributed to the infection. Hospitalization and clinical data were collected from medical records.

RESULTS: The prevalence of myalgia as COVID-19-associated symptom was 29.82% (n = 389) at hospitalization (T0). The prevalence of post-COVID pain was 41.07% (n = 520) at T1, 34.29% (n = 434) at T2, and 28.47% (n = 360) at T3. The recovery exponential curve revealed a decrease trend visualizing that post-COVID pain improved over the time span investigated. Pain in the lower extremity and widespread pain were the most prevalent locations. Female sex (OR 1.507, 95% CI 1.047-2.169), pre-existing pain symptoms (OR 1.724, 95% CI 1.237-2.403), headache as onset-symptom (OR 2.374, 95% CI 1.550-3.639), days at hospital (OR 1.012, 95% CI 1.000-1.025), and presence of post-COVID pain at T1 (OR 13.243, 95% CI 9.428-18.601) were associated with post-COVID pain at T2. Only the presence of post-COVID pain at T1 (OR 5.383, 95% CI 3.896-7.439) was associated with post-COVID pain at T3.

CONCLUSION: Current results show a fluctuating evolution with a decreasing tendency of post-COVID pain during the first years after hospitalization. The development of post-COVID pain soon after SARS-CoV-2 infection predispose for long-lasting chronic pain.}, } @article {pmid38646408, year = {2024}, author = {Masuko, T and Sasai-Masuko, H}, title = {Efficacy of Original Neurofeedback Treatment Method for Brain Fog From COVID-19: A Case Report.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e56519}, pmid = {38646408}, issn = {2168-8184}, abstract = {Brain fog is one of the most well-known sequelae of long COVID. It causes cognitive problems, mostly short-term memory disturbances, attention impairments, and problems with concentration. Although trials for treatment methods for brain fog have been carried out worldwide, effective methods have not yet been reported. Neurofeedback is effective for several common disorders and symptoms, including anxiety, depression, headaches, and pain. Neurofeedback is also reported to improve cognitive functions, such as processing speed and executive functions, including attention, planning, organization, problem-solving, and performance. Furthermore, neurofeedback is effective for "chemofog" and "chemobrain," which occur after chemotherapy and cause cognitive impairments in a similar manner to brain fog. However, there have been no reports of neurofeedback treatments for brain fog. Therefore, we have started to develop an original neurofeedback treatment method for brain fog using a Z-score neurofeedback technique. In this study, we present the first case report of a patient who has successfully recovered from brain fog via neurofeedback. Pain and psychological assessments revealed that the patient's pain improved and that the patient recovered from anxiety. Electroencephalograph data revealed several noble findings. C4 was thought to be the most affected site by brain fog, and this improved after treatment. The percentage increase at alpha wavelengths increased at almost all sites, and beta 1, beta 2, beta 3, and Hi beta decreased at almost all sites. The increased values at theta and alpha wavelengths after the 1st and 2nd sessions and the decreased values at higher beta wavelengths, such as beta 3 and Hi beta, were shown at all sessions.}, } @article {pmid38642615, year = {2024}, author = {VanElzakker, MB and Bues, HF and Brusaferri, L and Kim, M and Saadi, D and Ratai, EM and Dougherty, DD and Loggia, ML}, title = {Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [[11]C]PBR28 PET correlates with vascular disease measures.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {713-723}, pmid = {38642615}, issn = {1090-2139}, support = {S10 RR019307/RR/NCRR NIH HHS/United States ; R01 DA047088/DA/NIDA NIH HHS/United States ; R21 NS130283/NS/NINDS NIH HHS/United States ; S10 RR023043/RR/NCRR NIH HHS/United States ; S10 RR023401/RR/NCRR NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; Male ; *Positron-Emission Tomography/methods ; Female ; Middle Aged ; Adult ; *Neuroinflammatory Diseases/diagnostic imaging ; *SARS-CoV-2 ; *Brain/diagnostic imaging/metabolism ; Post-Acute COVID-19 Syndrome ; Vascular Diseases/diagnostic imaging ; Aged ; Pyridines ; Pyrimidines ; }, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [[11]C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.}, } @article {pmid38641935, year = {2024}, author = {Samerton, P and Apiwattanakul, N and Assawawiroonhakarn, S and Sahakijpicharn, T and Thongchai, R and Techasaensiri, C and Boonsathorn, S and Chaisavaneeyakorn, S}, title = {Severe acute respiratory syndrome coronavirus 2 infection rate among pediatric patients with respiratory symptoms.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {66}, number = {1}, pages = {e15740}, doi = {10.1111/ped.15740}, pmid = {38641935}, issn = {1442-200X}, support = {RF_64011//Mahidol University/ ; P2050966//National Science and Technology Development Agency/ ; }, mesh = {Humans ; Child ; Female ; Child, Preschool ; Male ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cross-Sectional Studies ; Prospective Studies ; Obesity ; Dyspnea ; Cough/epidemiology/etiology ; Chest Pain ; }, abstract = {BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in children has been increasing worldwide since the onset of the pandemic. This study examined the risk factors and characteristics of COVID-19 among pediatric patients compared to other respiratory viral infections.

METHODS: This was a prospective cross-sectional study. Patients aged 0-18 years presenting with respiratory symptoms from October 2020 to December 2021 were included. Demographic and clinical data were reviewed.

RESULTS: In total, 738 pediatric patients were enrolled. Of these, 48.5% had COVID-19, and 41.3% were infected with another respiratory virus. The COVID-19 incidence increased from 0.5% during the original strain outbreak (October 2020 to March 2021) to 56.5% and 73.4% during the alpha (April to June 2021) and delta (July to December 2021) periods, respectively. Children aged 6-18 years, being female, obesity, exposure to household members with COVID-19, and the delta period were risk factors for COVID-19. Being aged 1-5 years, obesity, shortness of breath, productive cough, and chest pain were associated with COVID-19 pneumonia. Children aged 5-18 years, underlying neurological disease, a history of COVID-19 pneumonia, and the delta period were associated with long COVID.

CONCLUSIONS: Pediatric COVID-19 patients presenting with respiratory symptoms who are obese or have been exposed to household members with COVID-19 should be tested for COVID-19. COVID-19 patients who are obese, younger than five years old, or who present with shortness of breath, productive cough, or chest pain should be evaluated for pneumonia. COVID-19 patients with a history of COVID-19 pneumonia or underlying neurological disease should receive follow-up for long COVID.}, } @article {pmid38641397, year = {2024}, author = {Wills, CP and Perez, B and Moore, J}, title = {Coronavirus Disease 2019: Past, Present, and Future.}, journal = {Emergency medicine clinics of North America}, volume = {42}, number = {2}, pages = {415-442}, doi = {10.1016/j.emc.2024.02.002}, pmid = {38641397}, issn = {1558-0539}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 is one of the most impactful diseases experienced in the past century. While the official national health emergency concluded in May of 2023, coronavirus disease 2019 (COVID-19) continues to mutate. As the summer of 2023, all countries were experiencing a new surge of cases from the EG.5 Omicron variant. Additionally, a new genetically distinct Omicron descendant BA2.86 had been detected in multiple countries including the United States. This article seeks to offer lessons learned from the pandemic, summarize best evidence for current management of patients with COVID-19, and give insights into future directions with this disease.}, } @article {pmid38641060, year = {2024}, author = {Ye, G and Zhu, Y and Bao, W and Zhou, H and Lai, J and Zhang, Y and Xie, J and Ma, Q and Luo, Z and Ma, S and Guo, Y and Zhang, X and Zhang, M and Niu, X}, title = {The Long COVID Symptoms and Severity Score: Development, Validation, and Application.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {27}, number = {8}, pages = {1085-1091}, doi = {10.1016/j.jval.2024.04.009}, pmid = {38641060}, issn = {1524-4733}, mesh = {Humans ; *COVID-19/diagnosis ; *Severity of Illness Index ; Reproducibility of Results ; Female ; Psychometrics ; Male ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; SARS-CoV-2 ; Adult ; Quality of Life ; Self Report ; Aged ; Factor Analysis, Statistical ; }, abstract = {OBJECTIVES: The primary focus of this research is the proposition of a methodological framework for the clinical application of the long COVID symptoms and severity score (LC-SSS). This tool is not just a self-reported assessment instrument developed and validated but serves as a standardized, quantifiable means to monitor the diverse and persistent symptoms frequently observed in individuals with long COVID.

METHODS: A 3-stage process was used to develop, validate, and establish scoring standards for the LC-SSS. Validation measures included correlations with other patient-reported measures, confirmatory factor analysis, Cronbach's α for internal consistency, and test-retest reliability. Scoring standards were determined using K-means clustering, with comparative assessments made against hierarchical clustering and the Gaussian Mixture Model.

RESULTS: The LC-SSS showed correlations with EuroQol 5-Dimension 5-Level (rs = -0.55), EuroQol visual analog scale (rs = -0.368), Patient Health Questionnaire-9 (rs = 0.538), Beck Anxiety Inventory (rs = 0.689), and Insomnia Severity Index (rs = 0.516), confirming its construct validity. Structural validity was good with a comparative fit index of 0.969, with Cronbach's α of 0.93 indicating excellent internal consistency. Test-retest reliability was also satisfactory (intraclass correlation coefficient 0.732). K-means clustering identified 3 distinct severity categories in individuals living with long COVID, providing a basis for personalized treatment strategies.

CONCLUSIONS: The LC-SSS provides a robust and valid tool for assessing long COVID. The severity categories established via K-means clustering demonstrate significant variation in symptom severity, informing personalized treatment and improving care quality for patients with long COVID.}, } @article {pmid38640090, year = {2024}, author = {Chaze, M and Mériade, L and Rochette, C and Bailly, M and Bingula, R and Blavignac, C and Duclos, M and Evrard, B and Fournier, AC and Pelissier, L and Thivel, D and , }, title = {Relying on the French territorial offer of thermal spa therapies to build a care pathway for long COVID-19 patients.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0302392}, pmid = {38640090}, issn = {1932-6203}, mesh = {Humans ; *Critical Pathways ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/therapy ; France/epidemiology ; Delivery of Health Care ; }, abstract = {BACKGROUND: Work on long COVID-19 has mainly focused on clinical care in hospitals. Thermal spa therapies represent a therapeutic offer outside of health care institutions that are nationally or even internationally attractive. Unlike local care (hospital care, general medicine, para-medical care), their integration in the care pathways of long COVID-19 patients seems little studied. The aim of this article is to determine what place french thermal spa therapies can take in the care pathway of long COVID-19 patients.

METHODS: Based on the case of France, we carry out a geographic mapping analysis of the potential care pathways for long COVID-19 patients by cross-referencing, over the period 2020-2022, the available official data on COVID-19 contamination, hospitalisations in intensive care units and the national offer of spa treatments. This first analysis allows us, by using the method for evaluating the attractiveness of an area defined by David Huff, to evaluate the accessibility of each French department to thermal spas.

RESULTS: Using dynamic geographical mapping, this study describes two essential criteria for the integration of the thermal spa therapies offer in the care pathways of long COVID-19 patients (attractiveness of spa areas and accessibility to thermal spas) and three fundamental elements for the success of these pathways (continuity of the care pathways; clinical collaborations; adaptation of the financing modalities to each patient). Using a spatial attractiveness method, we make this type of geographical analysis more dynamic by showing the extent to which a thermal spa is accessible to long COVID-19 patients.

CONCLUSION: Based on the example of the French spa offer, this study makes it possible to place the care pathways of long COVID-19 patients in a wider area (at least national), rather than limiting them to clinical and local management in a hospital setting. The identification and operationalization of two geographical criteria for integrating a type of treatment such as a spa cure into a care pathway contributes to a finer conceptualization of the construction of healthcare pathways.}, } @article {pmid38639670, year = {2024}, author = {Carstens, M and Trujillo, J and Dolmus, Y and Rivera, C and Calderwood, S and Lejarza, J and López, C and Bertram, K}, title = {Adipose-derived stromal vascular fraction cells to treat long-term pulmonary sequelae of coronavirus disease 2019: 12-month follow-up.}, journal = {Cytotherapy}, volume = {26}, number = {9}, pages = {1076-1083}, doi = {10.1016/j.jcyt.2024.03.491}, pmid = {38639670}, issn = {1477-2566}, mesh = {Humans ; *COVID-19/therapy/complications ; Male ; Female ; Middle Aged ; *Mesenchymal Stem Cell Transplantation/methods ; *SARS-CoV-2 ; Follow-Up Studies ; *Mesenchymal Stem Cells/cytology ; *Adipose Tissue/cytology ; *Lung/pathology/diagnostic imaging ; Aged ; Respiratory Function Tests ; Adult ; Transplantation, Autologous ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {BACKGROUND AIMS: Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID.

METHODS: Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung.

RESULTS: SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment.

CONCLUSIONS: It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID.}, } @article {pmid38638805, year = {2024}, author = {Ahuja, H and Badhwar, S and Edgell, H and Litoiu, M and Sergio, LE}, title = {Machine learning algorithms for detection of visuomotor neural control differences in individuals with PASC and ME.}, journal = {Frontiers in human neuroscience}, volume = {18}, number = {}, pages = {1359162}, pmid = {38638805}, issn = {1662-5161}, abstract = {The COVID-19 pandemic has affected millions worldwide, giving rise to long-term symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) infection, colloquially referred to as long COVID. With an increasing number of people experiencing these symptoms, early intervention is crucial. In this study, we introduce a novel method to detect the likelihood of PASC or Myalgic Encephalomyelitis (ME) using a wearable four-channel headband that collects Electroencephalogram (EEG) data. The raw EEG signals are processed using Continuous Wavelet Transform (CWT) to form a spectrogram-like matrix, which serves as input for various machine learning and deep learning models. We employ models such as CONVLSTM (Convolutional Long Short-Term Memory), CNN-LSTM, and Bi-LSTM (Bidirectional Long short-term memory). Additionally, we test the dataset on traditional machine learning models for comparative analysis. Our results show that the best-performing model, CNN-LSTM, achieved an accuracy of 83%. In addition to the original spectrogram data, we generated synthetic spectrograms using Wasserstein Generative Adversarial Networks (WGANs) to augment our dataset. These synthetic spectrograms contributed to the training phase, addressing challenges such as limited data volume and patient privacy. Impressively, the model trained on synthetic data achieved an average accuracy of 93%, significantly outperforming the original model. These results demonstrate the feasibility and effectiveness of our proposed method in detecting the effects of PASC and ME, paving the way for early identification and management of the condition. The proposed approach holds significant potential for various practical applications, particularly in the clinical domain. It can be utilized for evaluating the current condition of individuals with PASC or ME, and monitoring the recovery process of those with PASC, or the efficacy of any interventions in the PASC and ME populations. By implementing this technique, healthcare professionals can facilitate more effective management of chronic PASC or ME effects, ensuring timely intervention and improving the quality of life for those experiencing these conditions.}, } @article {pmid38638307, year = {2024}, author = {Zhao, J and Xia, F and Jiao, X and Lyu, X}, title = {Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1367974}, pmid = {38638307}, issn = {1664-2295}, abstract = {Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca[2+].}, } @article {pmid38638196, year = {2024}, author = {Antoncecchi, V and Antoncecchi, E and Orsini, E and D'Ascenzo, G and Oliviero, U and Savino, K and Aloisio, A and Casalino, L and Lillo, A and Chiuini, E and Santoro, G and Manfrè, V and Rizzo, V and Zito, GB}, title = {High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.}, journal = {International journal of cardiology. Cardiovascular risk and prevention}, volume = {21}, number = {}, pages = {200267}, pmid = {38638196}, issn = {2772-4875}, abstract = {BACKGROUND: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE).

RESULTS: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus.

CONCLUSION: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.}, } @article {pmid38637960, year = {2024}, author = {Van Laake, T and Hitch, D}, title = {Supporting rehabilitation practice for COVID-19 recovery: a descriptive qualitative analysis of allied health perspectives.}, journal = {Australian health review : a publication of the Australian Hospital Association}, volume = {48}, number = {4}, pages = {469-475}, doi = {10.1071/AH23210}, pmid = {38637960}, issn = {1449-8944}, mesh = {Humans ; *COVID-19/rehabilitation ; *Qualitative Research ; *Focus Groups ; Female ; Male ; SARS-CoV-2 ; Adult ; Allied Health Personnel/psychology ; Attitude of Health Personnel ; Middle Aged ; Interviews as Topic ; Rehabilitation/methods ; }, abstract = {Objective The study aimed to explore the perspective of healthcare workers on the resources they need to provide quality rehabilitation for people recovering from coronavirus disease 2019 (COVID-19) infection. Methods A descriptive qualitative approach using reflexive thematic analysis was employed. Focus groups and interviews were performed with nine healthcare workers (one intensive care unit physiotherapist, one respiratory therapist and seven occupational therapists) with experience treating patients recovering from COVID-19 infection within hospital and in the community. Verbatim transcripts were coded and analysed for themes. Results Healthcare workers perceive an urgent need for resources about recovery from COVID-19 infection to support quality care. They particularly want detailed guidance about potential trajectories of recovery, and what should be expected over time for people with long COVID. Many observed that this group of patients had higher oxygen requirement and experienced slower recovery than others with serious respiratory conditions. Supports for quality care do exist but were not perceived as sufficient by participants. They want any new resources developed to be accessible, quick to access and targeted to specific healthcare worker roles and services settings. Participants identified several barriers to accessing practice supports, including the time poor nature of health care and financial costs to both patients and healthcare workers. Conclusion Healthcare workers perceive an urgent need for the development of resources to support quality rehabilitation for people recovering from COVID-19 infection, to support best outcomes for this group of patients. Any resources developed must consider identified barriers to their access and use to maximise their impact.}, } @article {pmid38637239, year = {2024}, author = {Kooner, HK and Sharma, M and McIntosh, MJ and Dhaliwal, I and Nicholson, JM and Kirby, M and Svenningsen, S and Parraga, G}, title = {[129]Xe MRI Ventilation Textures and Longitudinal Quality-of-Life Improvements in Long-COVID.}, journal = {Academic radiology}, volume = {31}, number = {9}, pages = {3825-3836}, doi = {10.1016/j.acra.2024.03.014}, pmid = {38637239}, issn = {1878-4046}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Magnetic Resonance Imaging/methods ; Male ; Female ; Middle Aged ; *Quality of Life ; *Xenon Isotopes ; Aged ; Machine Learning ; Longitudinal Studies ; SARS-CoV-2 ; Lung/diagnostic imaging ; }, abstract = {RATIONALE AND OBJECTIVES: It remains difficult to predict longitudinal outcomes in long-COVID, even with chest CT and functional MRI. [129]Xe MRI reflects airway dysfunction, measured using ventilation defect percent (VDP) and in long-COVID patients, MRI VDP was abnormal, suggestive of airways disease. While MRI VDP and quality-of-life improved 15-month post-COVID infection, both remained abnormal. To better understand the relationship of airways disease and quality-of-life improvements in patients with long-COVID, we extracted [129]Xe ventilation MRI textures and generated machine-learning models in an effort to predict improved quality-of-life, 15-month post-infection.

MATERIALS AND METHODS: Long-COVID patients provided written-informed consent to 3-month and 15-month post-infection visits. Pyradiomics was used to extract [129]Xe ventilation MRI texture features, which were ranked using a Random-Forest classifier. Top-ranking features were used in classification models to dichotomize patients based on St. George's Respiratory Questionnaire (SGRQ) score improvement greater than the minimal-clinically-important-difference (MCID). Classification performance was evaluated using the area under the receiver-operator-characteristic-curve (AUC), sensitivity, and specificity.

RESULTS: 120 texture features were extracted from [129]Xe ventilation MRI in 44 long-COVID participants (54 ± 14 years), including 30 (52 ± 12 years) with ΔSGRQ≥MCID and 14 (58 ± 18 years) with ΔSGRQ
CONCLUSION: A machine learning model exclusively trained on [129]Xe MRI ventilation textures explained improved SGRQ-scores 12 months later, and outperformed clinical models. Their unique spatial-intensity information helps build our understanding about long-COVID airway dysfunction.}, } @article {pmid38637200, year = {2024}, author = {Lee, JD and Woodruff, TM}, title = {Complement(ing) long-COVID thromboinflammation and pathogenesis.}, journal = {Trends in immunology}, volume = {45}, number = {6}, pages = {397-399}, doi = {10.1016/j.it.2024.04.001}, pmid = {38637200}, issn = {1471-4981}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Complement System Proteins/immunology/metabolism ; Thromboinflammation/immunology ; Blood Coagulation/immunology ; Post-Acute COVID-19 Syndrome ; Complement Activation/immunology ; Antibodies, Viral/immunology ; }, abstract = {The persistence or recurrence of symptoms after acute SARS-CoV-2 infection, termed 'long COVID', presents a formidable challenge to global healthcare systems. Recent research by Cervia-Hasler and colleagues delves into the intricate immunological landscape in patients with long COVID, demonstrating an interplay between complement and coagulation, driven by antiviral antibodies and tissue damage.}, } @article {pmid38636655, year = {2024}, author = {Bradley, J and Xu, Q and Touloumes, N and Lusciks, E and Ali, T and Huang, EC and Chen, J and Ghafghazi, S and Arnold, FW and Kong, M and Huang, J and Cavallazzi, R and , }, title = {Association of pulmonary function test abnormalities and quality-of-life measures after COVID-19 infection.}, journal = {The American journal of the medical sciences}, volume = {368}, number = {2}, pages = {112-121}, pmid = {38636655}, issn = {1538-2990}, support = {P30 ES030283/ES/NIEHS NIH HHS/United States ; R01 AI172873/AI/NIAID NIH HHS/United States ; R01 HL158779/HL/NHLBI NIH HHS/United States ; U18 TR003787/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/psychology/physiopathology/epidemiology/complications ; *Quality of Life ; Male ; Female ; Middle Aged ; *Respiratory Function Tests ; Prospective Studies ; Aged ; Adult ; Surveys and Questionnaires ; SARS-CoV-2 ; Anxiety ; }, abstract = {BACKGROUND: Long-COVID is a multisystem disease that can lead to significant impairments in health-related quality of life (HRQoL). Following COVID-19 infection, abnormalities on pulmonary function tests (PFT) are common. The primary aim of this study is to evaluate for any correlation between PFT abnormalities and impairment in HRQoL scores following COVID-19 infection.

METHODS: This is an analysis of a prospective cohort of patients in Louisville, KY who were infected with COVID-19. Data collected included demographics, past medical history, laboratory tests, PFTs, and several HRQoL questionnaires such as the EuroQol 5 Dimension HRQoL questionnaire (EQ-5D-5 L), Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire (PHQ-9), and Posttraumatic stress disorder checklist for DSM-5 (PCL-5). Descriptive statistics were performed, comparing PFTs (normal vs abnormal) and time since COVID-19 infection (3- vs 6- vs ≥ 12 months).

RESULTS: There were no significant differences in FEV1, FVC, or the percentage of patients with abnormal PFTs over time after COVID-19 infection. Following COVID-19, patients with normal PFTs had worse impairment in mobility HRQoL scores and change in GAD-7 scores over time. There were no differences over time in any of the HRQoL scores among patients with abnormal PFTs.

CONCLUSIONS: Among patients with an abnormal PFT, there was no temporal association with HRQoL scores as measured by EQ-5D-5 L, GAD-7, PHQ-9, and PCL-5. Among patients with a normal PFT, mobility impairment and anxiety may be associated with COVID-19 infection. Following COVID-19 infection, impairment in HRQoL scores is not completely explained by the presence of abnormalities on spirometry.}, } @article {pmid38634418, year = {2024}, author = {Clutterbuck, D and Ramasawmy, M and Pantelic, M and Hayer, J and Begum, F and Faghy, M and Nasir, N and Causer, B and Heightman, M and Allsopp, G and Wootton, D and Khan, MA and Hastie, C and Jackson, M and Rayner, C and Brown, D and Parrett, E and Jones, G and Clarke, R and Mcfarland, S and Gabbay, M and Banerjee, A and Alwan, NA and , }, title = {Barriers to healthcare access and experiences of stigma: Findings from a coproduced Long Covid case-finding study.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {2}, pages = {e14037}, pmid = {38634418}, issn = {1369-7625}, support = {COV-LT2-0043//National Institute for Health Research (NIHR)/ ; NIHR300669//National Institute for Health Research (NIHR)/ ; //NIHR Applied Research Collaboration (ARC) Wessex/ ; //National Institute of Health and Care Research Applied Research Collaboration North West Coast (ARC NWC)/ ; }, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Social Stigma ; Mental Health ; Health Services Accessibility ; }, abstract = {BACKGROUND AND AIM: Long Covid is often stigmatised, particularly in people who are disadvantaged within society. This may prevent them from seeking help and could lead to widening health inequalities. This coproduced study with a Community Advisory Board (CAB) of people with Long Covid aimed to understand healthcare and wider barriers and stigma experienced by people with probable Long Covid.

METHODS: An active case finding approach was employed to find adults with probable, but not yet clinically diagnosed, Long Covid in two localities in London (Camden and Merton) and Derbyshire, England. Interviews explored the barriers to care and the stigma faced by participants and were analysed thematically. This study forms part of the STIMULATE-ICP Collaboration.

FINDINGS: Twenty-three interviews were completed. Participants reported limited awareness of what Long Covid is and the available pathways to management. There was considerable self-doubt among participants, sometimes reinforced by interactions with healthcare professionals (HCPs). Participants questioned their deservedness in seeking healthcare support for their symptoms. Hesitancy to engage with healthcare services was motivated by fear of needing more investigation and concerns regarding judgement about the ability to carry out caregiving responsibilities. It was also motivated by the complexity of the clinical presentation and fear of all symptoms being attributed to poor mental health. Participants also reported trying to avoid overburdening the health system. These difficulties were compounded by experiences of stigma and discrimination. The emerging themes reaffirmed a framework of epistemic injustice in relation to Long Covid, where creating, interpreting and conveying knowledge has varied credibility based on the teller's identity characteristics and/or the level of their interpretive resources.

CONCLUSION: We have codeveloped recommendations based on the findings. These include early signposting to services, dedicating protected time to listening to people with Long Covid, providing a holistic approach in care pathways, and working to mitigate stigma. Regardless of the diagnosis, people experiencing new symptoms must be encouraged to seek timely medical help. Clear public health messaging is needed among communities already disadvantaged by epistemic injustice to raise awareness of Long Covid, and to share stories that encourage seeking care and to illustrate the adverse effects of stigma.

This study was coproduced with a CAB made up of 23 members including HCPs, people with lived experience of Long Covid and other stakeholders.}, } @article {pmid38633561, year = {2023}, author = {Sarıcaoğlu, EM and Çınar, G and Azap, A and Bayar, MK and Togay-Işıkay, C and Kutlay, Ş and İbiş, S}, title = {Dark Side of the COVID-19 Pandemic; 'Long COVID'.}, journal = {Infectious diseases & clinical microbiology}, volume = {5}, number = {3}, pages = {205-211}, pmid = {38633561}, issn = {2667-646X}, abstract = {OBJECTIVE: Besides its morbidity and mortality all over the world, SARS-CoV-2 infection maintains its importance with prolonged symptoms after acute disease. The post-infectious period including a heterogeneous group of symptoms is named 'long COVID'. This study aimed to describe persisting symptoms three months after COVID-19 and risk factors associated with 'long COVID'.

MATERIALS AND METHODS: This cross-sectional retrospective study included COVID-19 patients diagnosed with SARS-CoV-2 PCR positivity in the first 18 months of the COVID-19 pandemic, between March 2020 and September 2021. We conducted a survey in 2022 to inquire about the participants' symptoms that lasted three months or more after their own COVID-19 period. All patients were employees of one of the biggest national banks in Turkey. Participants answered a total of 31 questions over the phone. The presence of one or more symptoms persisting ≥3 months was defined as 'long COVID'. The risk factors associated with 'long COVID' were determined.

RESULTS: A total of 1301 patients were included in our study. The median age of patients was 40 (22-57), and 558 (42.9%) were women. 257 (19.8%) patients had 'long COVID' symptoms. The most prevalent symptoms were myalgia (14.3%), arthralgia (14.1%), and back pain (13.8%). Female gender (p=0.000, OR=2.19 [95% CI=1.655-2.904]) and diabetes mellitus (p=0.016, OR=2.43 [95% CI=1.177-5.017]) were found as independent risk factors for 'long COVID' by multivariant logistic regression analysis.

CONCLUSION: Female gender and diabetes mellitus are risk factors for 'long COVID'. Detecting patients with a high risk for developing 'long COVID' is crucial for their management during the COVID and post-COVID periods.}, } @article {pmid38633559, year = {2023}, author = {Yalçın-Çolak, N and Kader, Ç and Eren-Gök, Ş and Erbay, A}, title = {Long-Term Symptoms and Quality of Life in Persons with COVID-19.}, journal = {Infectious diseases & clinical microbiology}, volume = {5}, number = {3}, pages = {212-220}, pmid = {38633559}, issn = {2667-646X}, abstract = {OBJECTIVE: After three years since the first cases of COVID-19, many people suffer from post-COVID symptoms, reducing their quality of life. In this study, we aimed to evaluate the symptoms and prevalence of long COVID and its effect on the quality of life and also the effect of SARS-CoV-2 vaccine on the quality of life.

MATERIALS AND METHODS: Patients with COVID-19 between April 01, 2020, and December 31, 2021, were evaluated with a survey at least three and at most 12 months (mean 7.43±3.3 months) after diagnosis. Patients answered the questions face-to-face or via telephone interview. The survey included questionnaires on demographic features, current complaints, and complaints that persisted or developed after recovery, Short Form 36 Health Survey (SF-36), and European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) Scale.

RESULTS: The study was conducted with 521 participants, 81% complaining of post-COVID symptoms. The most common symptoms were fatigue and shortness of breath. Long COVID was found to significantly reduce the quality of life in both sub-dimensions of the scale. Compared to SF-36 Turkish population norms, all participants showed a significant decrease in quality of life subscales. Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was found to improve quality of life and reduce long-term COVID-19 symptoms.

CONCLUSION: COVID-19 has significantly affected quality of life. Post-illness follow-up of people with COVID-19 is important to provide patients with medical, physical, and psychosocial rehabilitation support. SARS-COV-2 vaccine reduces the negative effects of COVID-19 on quality of life. For this reason, the community should be made aware of vaccination, and COVID-19 vaccination rates should be increased in the community.}, } @article {pmid38632311, year = {2024}, author = {Phetsouphanh, C and Jacka, B and Ballouz, S and Jackson, KJL and Wilson, DB and Manandhar, B and Klemm, V and Tan, HX and Wheatley, A and Aggarwal, A and Akerman, A and Milogiannakis, V and Starr, M and Cunningham, P and Turville, SG and Kent, SJ and Byrne, A and Brew, BJ and Darley, DR and Dore, GJ and Kelleher, AD and Matthews, GV}, title = {Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3315}, pmid = {38632311}, issn = {2041-1723}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; CD8-Positive T-Lymphocytes ; Quality of Life ; SARS-CoV-2 ; Antibodies, Viral ; }, abstract = {This study investigates the humoral and cellular immune responses and health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared to age and gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, and higher neutralizing capacity up to 8 months post-infection. Increased spike-specific and nucleocapsid-specific CD4[+] T cells, PD-1, and TIM-3 expression on CD4[+] and CD8[+] T cells were observed at 3 and 8 months, but these differences do not persist at 24 months. Some LC participants had detectable IFN-γ and IFN-β, that was attributed to reinfection and antigen re-exposure. Single-cell RNA sequencing at the 24 month timepoint shows similar immune cell proportions and reconstitution of naïve T and B cell subsets in LC and MC. No significant differences in exhaustion scores or antigen-specific T cell clones are observed. These findings suggest resolution of immune activation in LC and return to comparable immune responses between LC and MC over time. Improvement in self-reported health-related quality of life at 24 months was also evident in the majority of LC (62%). PTX3, CRP levels and platelet count are associated with improvements in health-related quality of life.}, } @article {pmid38631816, year = {2024}, author = {Matthews, B and Datey Chakrabarty, A and Chakrabarty, A}, title = {Long-term cognitive effects of COVID-19 studied with repeated neuropsychological testing.}, journal = {BMJ case reports}, volume = {17}, number = {4}, pages = {}, pmid = {38631816}, issn = {1757-790X}, mesh = {Female ; Humans ; *Attention Deficit Disorder with Hyperactivity/psychology ; Cognition/physiology ; *COVID-19/complications ; Executive Function/physiology ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; Middle Aged ; }, abstract = {COVID-19 has a wide range of clinical manifestations. Apart from respiratory symptoms, neurological manifestations and cognitive impairment are commonly seen. Due to lack of a clear consensus on the definition of long COVID a pragmatic approach of assessing change from neurological baseline has become prevalent. We present the case of a high functioning woman in her late 40s who had a mild course of acute illness but developed cognitive difficulties. No organic causes for her cognitive difficulties were found. Neuropsychological testing showed impairment in right frontal lobe functioning. The patient showed a response to empirical treatment with Attention deficit hyperactivity disorder (ADHD) medications. Repeat neuropsychological testing 1 year later showed continued dysfunction in executive functioning. We present the details of her test findings and discuss the proposed pathophysiology behind neurocognitive effects of long COVID.}, } @article {pmid38631806, year = {2024}, author = {Kane, AS and Godfrey, M and Noval Rivas, M and Arditi, M and Fasano, A and Yonker, LM}, title = {The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID.}, journal = {Annual review of virology}, volume = {11}, number = {1}, pages = {327-341}, doi = {10.1146/annurev-virology-093022-011839}, pmid = {38631806}, issn = {2327-0578}, mesh = {Humans ; *COVID-19/complications/immunology/virology ; *Systemic Inflammatory Response Syndrome/diagnosis/virology ; Child ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; *Dysbiosis ; Gastrointestinal Microbiome ; }, abstract = {The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.}, } @article {pmid38630952, year = {2024}, author = {McAlpine, L and Zubair, AS and Joseph, P and Spudich, S}, title = {Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {11}, number = {3}, pages = {e200244}, pmid = {38630952}, issn = {2332-7812}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Small Fiber Neuropathy ; Case-Control Studies ; Retrospective Studies ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Immunoglobulins, Intravenous ; *COVID-19 ; *Autonomic Nervous System Diseases ; }, abstract = {OBJECTIVES: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.

METHODS: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention.

RESULTS: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02).

DISCUSSION: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence. It is a retrospective cohort study.}, } @article {pmid38628706, year = {2024}, author = {Reier-Nilsen, T and Grønneberg, C and Røine, S and Nordlund, B}, title = {Assessment of lung function variability documents airflow limitation in many patients with long covid.}, journal = {Heliyon}, volume = {10}, number = {8}, pages = {e29261}, pmid = {38628706}, issn = {2405-8440}, abstract = {BACKGROUND: It is estimated that 65 million people worldwide suffer from long covid (LC). Many LC symptoms are also reported by patients with airflow limitation, used to confirm asthma. The primary aim was to detect airflow limitation in LC patients by a methacholine bronchial provocation test (BPT) and if negative, by evaluation of diurnal variability in forced expiratory flow in 1 second (FEV1) over a two-weeks' period. The second aim was to assess responsiveness to asthma treatment on diurnal FEV1 variability and LC symptoms.

METHODS: Patients with LC for at least six months were recruited in this open diagnostic study. Burden of LC symptoms were reported on a 10-point Likert scale (0 = not troubled, 10 = extremely troubled) at inclusion and after three weeks' asthma treatment. A positive methacholine BPT was defined by an accumulated provocation dose (PD20)<8 μmol causing 20% fall in FEV1. App-based spirometer was used for diurnal FEV1 variability, deemed positive by diurnalvariability in FEV1 ≥12%.

RESULTS: Airflow limitation was documented by positive methacholine BPT in 8/30 (27%), or by excessive diurnal variability in FEV1 in 21/22 (95%) of the BPT negative LC patients. One patient dropped out due to personal issues. Three weeks' asthma treatment normalised mean diurnal FEV1 variability from 18.0% to 7.3%, p < 0.001. Significant reductions were observed for fatigue and dyspnoea, from 8.3 to 6.1, p < 0.001, and 3.0 to 0, p < 0.001, respectively.

CONCLUSION: This study indicate that airflow limitation may be detected in many LC patients if evaluation of diurnal variability in FEV1 is included in the diagnostics.}, } @article {pmid38628604, year = {2024}, author = {Anderson, GM and Cook, EH and Blakely, RD and Sutcliffe, JS and Veenstra-VanderWeele, J}, title = {Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration.}, journal = {Journal of inflammation research}, volume = {17}, number = {}, pages = {2169-2172}, pmid = {38628604}, issn = {1178-7031}, abstract = {We believe there are serious problems with a recently published and highly publicized paper entitled "Serotonin reduction in post-acute sequelae of viral infection." The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement. In the "Discussion" section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, "Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment", it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs' effective inhibition of the platelet serotonin transporter. Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.}, } @article {pmid38628054, year = {2024}, author = {Bachrach, RL and Tighe, CA and Beyer, N and Hruska, K and Phares, A and Atchison, K and Baniak, L and Haas, G and Bramoweth, AD}, title = {Sleep and Alcohol Use Among Veterans Living With Long COVID.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241246992}, pmid = {38628054}, issn = {2150-1327}, support = {IK2 HX003087/HX/HSRD VA/United States ; IK2 RX003393/RX/RRD VA/United States ; }, mesh = {United States/epidemiology ; Humans ; *Veterans ; Post-Acute COVID-19 Syndrome ; United States Department of Veterans Affairs ; *COVID-19/epidemiology ; Ethanol ; *Sleep Wake Disorders/epidemiology ; Qualitative Research ; }, abstract = {OBJECTIVES: Study objectives were to: (1) better understand sleep experiences and unhealthy alcohol use among Veterans with long COVID and (2) explore providers' perceptions of barriers and facilitators to delivering evidence-based care for sleep problems and unhealthy alcohol use in patients with long COVID.

METHODS: VA electronic health records were used to conduct chart reviews (n = 57) of patients evaluated in a VA COVID-19 Recovery Clinic during 1 calendar year; semi-structured interviews were completed with Veterans (n = 5) and clinicians (n = 7) recruited from the clinic. Veteran participants also completed quantitative, self-report measures assessing sleep- and alcohol-related experiences and behaviors.

RESULTS: Data from chart reviews and interviews suggested that Veterans with long COVID often had pre-existing sleep problems that were exacerbated during long COVID. Patients and providers agreed that sleep interventions would be beneficial and acceptable in the COVID-19 Recovery clinic. Conversely, few Veterans with long COVID had a pre-existing alcohol use disorder (AUD) diagnosis; alcohol use occurred less frequently and was less often discussed between patients and providers. Providers had mixed viewpoints on delivering alcohol-related care in the clinic; some were highly amenable, others were unsure whether patients would be receptive.

CONCLUSIONS: This study is among the first to take a mixed-method approach to understanding experiences of sleep-wake behaviors and unhealthy alcohol use in Veterans with long COVID. Characterizing sleep and alcohol-related experiences, examining associations with functioning, and exploring perspectives on treatment approaches is critical to support efforts to refine, personalize, and optimize evidence-based sleep and alcohol care for Veterans living with long COVID.}, } @article {pmid38627595, year = {2024}, author = {Greene, C and Connolly, R and Brennan, D and Laffan, A and O'Keeffe, E and Zaporojan, L and O'Callaghan, J and Thomson, B and Connolly, E and Argue, R and Meaney, JFM and Martin-Loeches, I and Long, A and Cheallaigh, CN and Conlon, N and Doherty, CP and Campbell, M}, title = {Author Correction: Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.}, journal = {Nature neuroscience}, volume = {27}, number = {5}, pages = {1019}, doi = {10.1038/s41593-024-01644-0}, pmid = {38627595}, issn = {1546-1726}, support = {20/COV/0312//Science Foundation Ireland (SFI)/ ; 21/SPP/3732//Science Foundation Ireland (SFI)/ ; }, } @article {pmid38627327, year = {2024}, author = {Niewolik, J and Mikuteit, M and Klawitter, S and Schröder, D and Stölting, A and Vahldiek, K and Heinemann, S and Müller, F and Behrens, G and Klawonn, F and Dopfer-Jablonka, A and Steffens, S}, title = {Cluster analysis of long COVID symptoms for deciphering a syndrome and its long-term consequence.}, journal = {Immunologic research}, volume = {72}, number = {4}, pages = {605-613}, pmid = {38627327}, issn = {1559-0755}, support = {ZW7-85152953//European Regional Development Fund/ ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Cluster Analysis ; *SARS-CoV-2 ; Female ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Aged ; Severity of Illness Index ; }, abstract = {The long-term symptoms of COVID-19 are the subject of public and scientific discussions. Understanding how those long COVID symptoms co-occur in clusters of syndromes may indicate the pathogenic mechanisms of long COVID. Our study objective was to cluster the different long COVID symptoms. We included persons who had a COVID-19 and assessed long-term symptoms (at least 4 weeks after first symptoms). Hierarchical clustering was applied to the symptoms as well as to the participants based on the Euclidean distance h of the log-values of the answers on symptom severity. The distribution of clusters within our cohort is shown in a heat map.From September 2021 to November 2023, 2371 persons with persisting long COVID symptoms participated in the study. Self-assessed long COVID symptoms were assigned to three symptom clusters. Cluster A unites rheumatological and neurological symptoms, cluster B includes neuro-psychological symptoms together with cardiorespiratory symptoms, and a third cluster C shows an association of general infection signs, dermatological and otology symptoms. A high proportion of the participants (n = 1424) showed symptoms of all three clusters. Clustering of long COVID symptoms reveals similarities to the symptomatology of already described syndromes such as the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or rheumatological autoinflammatory diseases. Further research may identify serological parameters or clinical risk factors associated with the shown clusters and might improve our understanding of long COVID as a systemic disease. Furthermore, multimodal treatments can be developed and scaled for symptom clusters and associated impairments.}, } @article {pmid38627175, year = {2024}, author = {Mühlhauser, I and Pantel, J and Meyer, G}, title = {[Evaluation of the public health measures introduced during the coronavirus pandemic: Evidence-based risk communication must be a central topic].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {186}, number = {}, pages = {35-42}, doi = {10.1016/j.zefq.2024.03.004}, pmid = {38627175}, issn = {2212-0289}, mesh = {*COVID-19/prevention & control/epidemiology ; Humans ; Germany ; *Evidence-Based Medicine ; *Pandemics/prevention & control ; *SARS-CoV-2 ; Public Health ; Communication ; Risk Assessment ; Decision Making ; }, abstract = {Evidence-based and comprehensible health information is a key element of evidence-based medicine and public health. The goal is informed decision-making based on realistic estimations of health risks and accurate expectations about benefits and harms of interventions. In Germany, standards of evidence-based risk information were poorly followed during the COVID-19 pandemic. Frequently, public information was biased, fragmentary and misleading. Pandemic-related threat scenarios induced emotional distress and unnecessary anxiety. A systematic and comprehensive evaluation of the pandemic measures is crucial, but still pending in Germany. A critical analysis of risk communication by experts, politicians and the media during the pandemic should be a key element of the evaluation process. Evaluation of decision making and media reporting during the pandemic should improve preparedness for future crises.}, } @article {pmid38623400, year = {2024}, author = {Glover, NA and Ivanova, O and Sathar, F and Riess, F and Shambhu, RR and Mekota, AM and Zurba, L and Menezes, C and Alexandra van Blydenstein, S and Kalla, I and Hoelscher, M and Saathoff, E and Charalambous, S and Rachow, A}, title = {Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102588}, pmid = {38623400}, issn = {2589-5370}, abstract = {BACKGROUND: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV.

METHODS: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT.

FINDINGS: We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300 m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6% <80% predicted), DLCO (53.4% <80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200 cells/mm[3], BMI <18.5 kg/m[2] and >35 kg/m[2], and initial COVID-19 severity.

INTERPRETATION: This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies.

FUNDING: The Bavarian State Ministry of Science and Arts.}, } @article {pmid38623399, year = {2024}, author = {Jeffrey, K and Woolford, L and Maini, R and Basetti, S and Batchelor, A and Weatherill, D and White, C and Hammersley, V and Millington, T and Macdonald, C and Quint, JK and Kerr, R and Kerr, S and Shah, SA and Rudan, I and Fagbamigbe, AF and Simpson, CR and Katikireddi, SV and Robertson, C and Ritchie, L and Sheikh, A and Daines, L}, title = {Prevalence and risk factors for long COVID among adults in Scotland using electronic health records: a national, retrospective, observational cohort study.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102590}, pmid = {38623399}, issn = {2589-5370}, abstract = {BACKGROUND: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development.

METHODS: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98-99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status.

FINDINGS: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38-67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4-26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive.

INTERPRETATION: The prevalence of long COVID presenting in general practice was estimated to be 0.02-1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach.

FUNDING: Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.}, } @article {pmid38622709, year = {2024}, author = {Hersh, Z and Weisband, YL and Bogan, A and Leibovich, A and Obolski, U and Nevo, D and Gilad-Bachrach, R}, title = {Impact of Long-COVID in children: a large cohort study.}, journal = {Child and adolescent psychiatry and mental health}, volume = {18}, number = {1}, pages = {48}, pmid = {38622709}, issn = {1753-2000}, abstract = {BACKGROUND: The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3-6 months after the date of diagnosis.

METHODS: A retrospective study of all Clalit Health Services members in Israel aged 1-16 years who tested positive for SARS-CoV-2 between April 1, 2020 and March 31, 2021. Controls, who had no previous diagnosis of COVID-19, were one-to-one matched to 65,548 COVID-19-positive children and teens, and were assigned the infection dates of their matches as their index date. Matching included age, sex, socio-economic score, and societal sector. Individuals were excluded from the study if they had severe medical conditions before the diagnosis such as cancer, diabetes, chronic respiratory diseases, and/or abnormal physiological development. Generalized Estimating Equations were used to estimate the associations between COVID-19 and the use of medical services. The analysis focused on the 3-6 months after the infection date. Adjustments were made for demographics and for the use of medical services 6-12 and 3-6 months before the infection date. The latter was necessary because of observed disparities in medical service utilization between the groups before the COVID-19 diagnosis, despite the matching process.

RESULTS: Statistically significant differences were only found for referrals for mental health services [adjusted relative-risk (RR) 1·51, 95%CI 1·15 - 1·96; adjusted risk-difference (RD) 0·001, 95%CI 0·0006 - 0·002], and medication prescriptions of any kind (RR 1·03, 95%CI 1·01-1·06; RD 0·01 95%CI 0·004 - 0·02).

CONCLUSIONS: The significant increase in medication prescriptions and mental health service referrals support the hypothesis that COVID-19 is associated with long-lasting morbidities in children and adolescents aged 1-16 years. However, the risk difference in both instances was small, suggesting a minor impact on medical services.}, } @article {pmid38622352, year = {2024}, author = {Chan, JF and Yuan, S and Chu, H and Sridhar, S and Yuen, KY}, title = {COVID-19 drug discovery and treatment options.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {7}, pages = {391-407}, pmid = {38622352}, issn = {1740-1534}, mesh = {Humans ; *Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 Drug Treatment ; *Drug Discovery ; *SARS-CoV-2/drug effects ; *COVID-19/virology ; Animals ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality, and serious social and economic disruptions worldwide. Unvaccinated or incompletely vaccinated older individuals with underlying diseases are especially prone to severe disease. In patients with non-fatal disease, long COVID affecting multiple body systems may persist for months. Unlike SARS-CoV and Middle East respiratory syndrome coronavirus, which have either been mitigated or remained geographically restricted, SARS-CoV-2 has disseminated globally and is likely to continue circulating in humans with possible emergence of new variants that may render vaccines less effective. Thus, safe, effective and readily available COVID-19 therapeutics are urgently needed. In this Review, we summarize the major drug discovery approaches, preclinical antiviral evaluation models, representative virus-targeting and host-targeting therapeutic options, and key therapeutics currently in clinical use for COVID-19. Preparedness against future coronavirus pandemics relies not only on effective vaccines but also on broad-spectrum antivirals targeting conserved viral components or universal host targets, and new therapeutics that can precisely modulate the immune response during infection.}, } @article {pmid38620128, year = {2023}, author = {W, O and N, N and M, C and A, SM and G, J and Jh, H and Jc, F and K, P and B, W and A, B and A, M}, title = {Acute Onset of Mania and Psychosis in the Context of Long-COVID: A Case Study.}, journal = {Psychiatry research case reports}, volume = {}, number = {}, pages = {100138}, pmid = {38620128}, issn = {2773-0212}, abstract = {Acute phase COVID-19 has been associated with an increased risk for several mental health conditions, but less is known about the interaction of long COVID and mental illness. Prior reports have linked long COVID to PTSD, depression, anxiety, obsessive compulsive symptoms, and insomnia. This case report describes a novel presentation of mania arising in the context of long COVID symptoms with attention given to possible interacting etiological pathways. The case report also highlights the need for integrated, multidisciplinary treatment to support patients whose alarming, confusing, and multidetermined symptoms increase risk of psychological deterioration.}, } @article {pmid38619233, year = {2024}, author = {Tomasiewicz, K and Woron, J and Kobayashi, A and Krasinski, Z and Rydzewska, G and Szymanski, FM}, title = {Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.}, journal = {Polish archives of internal medicine}, volume = {134}, number = {5}, pages = {}, doi = {10.20452/pamw.16728}, pmid = {38619233}, issn = {1897-9483}, mesh = {Humans ; *COVID-19/complications/therapy ; Poland ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Post-COVID-19 syndrome, also known as long COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from an acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. Pathogenesis of post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy are crucial for understanding and effectively treating this complex and multifaceted condition.}, } @article {pmid38618011, year = {2024}, author = {Rizzi, G and Albanese, E}, title = {Reply to the letter to the editor "before attributing impaired cognition in the elderly to COVID-19, all influencing factors must be considered".}, journal = {Brain, behavior, & immunity - health}, volume = {37}, number = {}, pages = {100740}, pmid = {38618011}, issn = {2666-3546}, } @article {pmid38617937, year = {2024}, author = {de Bruijn, S and van Hoek, AJ and Mutubuki, EN and Knoop, H and Slootweg, J and Tulen, AD and Franz, E and van den Wijngaard, CC and van der Maaden, T}, title = {Lower prevalence of post-Covid-19 Condition following Omicron SARS-CoV-2 infection.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e28941}, pmid = {38617937}, issn = {2405-8440}, abstract = {OBJECTIVES: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections.

METHODS: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls.

RESULTS: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course.

CONCLUSIONS: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection.}, } @article {pmid38616282, year = {2024}, author = {Kirchberger, I and Meisinger, C and Warm, TD and Hyhlik-Dürr, A and Linseisen, J and Goßlau, Y}, title = {Longitudinal course and predictors of health-related quality of life, mental health, and fatigue, in non-hospitalized individuals with or without post COVID-19 syndrome.}, journal = {Health and quality of life outcomes}, volume = {22}, number = {1}, pages = {32}, pmid = {38616282}, issn = {1477-7525}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Mental Health ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/epidemiology ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; }, abstract = {BACKGROUND: Long-term information on health-related quality of life (HRQOL) and mental health of non-hospitalized individuals with "post COVID-19 syndrome" (PCS) is scarce. Thus, the objectives of the present study were to compare HRQOL and mental health of individuals with and without PCS in a German sample of non-hospitalized persons after SARS-CoV-2 infection, to characterize the long-term course up to 2 years and to identify predictors for post COVID-19 impairments.

METHODS: Individuals with past SARS-CoV-2 infection were examined at the University Hospital of Augsburg from November 2020 to May 2021 and completed a postal questionnaire between June and November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. HRQOL was assessed using the Veterans RAND 12-Item Health Survey, mental health was measured by the Patient Health Questionnaire and the Fatigue Asessment Scale was used to assess fatigue severity. Multivariable linear regression models with inverse probability weighting were used to determine the association between PCS and health outcomes.

RESULTS: From the 304 participants (58.2% women, median age 52 years), 210 (69.1%) were classified as having PCS in median 26 months after SARS-CoV-2 infection. Persons with PCS showed significantly more often depressive and anxiety disorders. PCS was independently and significantly associated with higher levels of depression, post-traumatic stress and fatigue, as well as poorer physical and mental HRQOL in median 9 months as well as 26 months after SARS-CoV-2 infection. A large number of acute symptoms and a prior diagnosis of depression were independently associated with poor mental health and HRQOL. While post-traumatic stress and mental HRQOL improved from 9 months to 26 months post infection onset, depressiveness, fatigue and physical HRQOL remained stable in both, persons with and without PCS.

CONCLUSIONS: PCS in non-hospitalized persons after SARS-CoV-2 infection is often associated with long-term impairments of mental health and HRQOL outcomes.}, } @article {pmid38616276, year = {2024}, author = {Greenhalgh, T and Darbyshire, JL and Lee, C and Ladds, E and Ceolta-Smith, J}, title = {What is quality in long covid care? Lessons from a national quality improvement collaborative and multi-site ethnography.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {159}, pmid = {38616276}, issn = {1741-7015}, support = {COV-LT-0016//National Institute for Health and Care Research/ ; }, mesh = {Humans ; Anthropology, Cultural ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; *Quality Improvement ; Multicenter Studies as Topic ; Clinical Studies as Topic ; }, abstract = {BACKGROUND: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called "postcode lottery" of care. The original aim of this study-to examine the nature of quality in long covid care and reduce unwarranted variation in services-evolved to focus on examining the reasons why standardizing care was so challenging in this condition.

METHODS: In 2021-2023, we ran a quality improvement collaborative across 10 UK sites. The dataset reported here was mostly but not entirely qualitative. It included data on the origins and current context of each clinic, interviews with staff and patients, and ethnographic observations at 13 clinics (50 consultations) and 45 multidisciplinary team (MDT) meetings (244 patient cases). Data collection and analysis were informed by relevant lenses from clinical care (e.g. evidence-based guidelines), improvement science (e.g. quality improvement cycles) and philosophy of knowledge.

RESULTS: Participating clinics made progress towards standardizing assessment and management in some topics; some variation remained but this could usually be explained. Clinics had different histories and path dependencies, occupied a different place in their healthcare ecosystem and served a varied caseload including a high proportion of patients with comorbidities. A key mechanism for achieving high-quality long covid care was when local MDTs deliberated on unusual, complex or challenging cases for which evidence-based guidelines provided no easy answers. In such cases, collective learning occurred through idiographic (case-based) reasoning, in which practitioners build lessons from the particular to the general. This contrasts with the nomothetic reasoning implicit in evidence-based guidelines, in which reasoning is assumed to go from the general (e.g. findings of clinical trials) to the particular (management of individual patients).

CONCLUSION: Not all variation in long covid services is unwarranted. Largely because long covid's manifestations are so varied and comorbidities common, generic "evidence-based" standards require much individual adaptation. In this complex condition, quality improvement resources may be productively spent supporting MDTs to optimise their case-based learning through interdisciplinary discussion. Quality assessment of a long covid service should include review of a sample of individual cases to assess how guidelines have been interpreted and personalized to meet patients' unique needs.

STUDY REGISTRATION: NCT05057260, ISRCTN15022307.}, } @article {pmid38615819, year = {2024}, author = {Lladós, G and Massanella, M and Paredes, R and Mateu, L}, title = {'Vagus Nerve Dysfunction in the Post-COVID-19 Condition' - Author's reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {7}, pages = {971-972}, doi = {10.1016/j.cmi.2024.04.005}, pmid = {38615819}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/complications ; *Vagus Nerve/physiopathology ; SARS-CoV-2 ; }, } @article {pmid38614374, year = {2024}, author = {Guarnieri, JW and Haltom, JA and Albrecht, YES and Lie, T and Olali, AZ and Widjaja, GA and Ranshing, SS and Angelin, A and Murdock, D and Wallace, DC}, title = {SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19.}, journal = {Pharmacological research}, volume = {204}, number = {}, pages = {107170}, doi = {10.1016/j.phrs.2024.107170}, pmid = {38614374}, issn = {1096-1186}, mesh = {Humans ; *COVID-19/metabolism/genetics/virology ; *SARS-CoV-2 ; *Mitochondria/metabolism/genetics ; *Oxidative Phosphorylation ; Reactive Oxygen Species/metabolism ; Epigenesis, Genetic ; Energy Metabolism ; Epigenomics ; Animals ; }, abstract = {To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.}, } @article {pmid38614106, year = {2024}, author = {Trinh, NT and Jödicke, AM and Català, M and Mercadé-Besora, N and Hayati, S and Lupattelli, A and Prieto-Alhambra, D and Nordeng, HM}, title = {Effectiveness of COVID-19 vaccines to prevent long COVID: data from Norway.}, journal = {The Lancet. Respiratory medicine}, volume = {12}, number = {5}, pages = {e33-e34}, doi = {10.1016/S2213-2600(24)00082-1}, pmid = {38614106}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 Vaccines ; *COVID-19/prevention & control/epidemiology ; Norway/epidemiology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Vaccine Efficacy ; Middle Aged ; Female ; Male ; Adult ; }, } @article {pmid38612641, year = {2024}, author = {Pulliam, L and Sun, B and McCafferty, E and Soper, SA and Witek, MA and Hu, M and Ford, JM and Song, S and Kapogiannis, D and Glesby, MJ and Merenstein, D and Tien, PC and Freasier, H and French, A and McKay, H and Diaz, MM and Ofotokun, I and Lake, JE and Margolick, JB and Kim, EY and Levine, SR and Fischl, MA and Li, W and Martinson, J and Tang, N}, title = {Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612641}, issn = {1422-0067}, support = {U01 HL146245/HL/NHLBI NIH HHS/United States ; R01 MH121121/MH/NIMH NIH HHS/United States ; U01 HL146208/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; KL2 TR001432/TR/NCATS NIH HHS/United States ; U01 HL146192/HL/NHLBI NIH HHS/United States ; U01 HL146242/HL/NHLBI NIH HHS/United States ; TL1 TR001431/TR/NCATS NIH HHS/United States ; P30 AI036214/AI/NIAID NIH HHS/United States ; I01 CX002322/CX/CSRD VA/United States ; P41 EB020594/EB/NIBIB NIH HHS/United States ; U01 HL146194/HL/NHLBI NIH HHS/United States ; U01 HL146241/HL/NHLBI NIH HHS/United States ; P30 AI027767/AI/NIAID NIH HHS/United States ; P30 AI050409/AI/NIAID NIH HHS/United States ; U01 HL146333/HL/NHLBI NIH HHS/United States ; U01 HL146205/HL/NHLBI NIH HHS/United States ; P30 MH116867/MH/NIMH NIH HHS/United States ; P30 AI073961/AI/NIAID NIH HHS/United States ; U01 HL146201/HL/NHLBI NIH HHS/United States ; P20 GM130423/GM/NIGMS NIH HHS/United States ; IK6 CX002519/CX/CSRD VA/United States ; U01 HL146193/HL/NHLBI NIH HHS/United States ; U01 HL146204/HL/NHLBI NIH HHS/United States ; U01 HL146202/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01 HL146240/HL/NHLBI NIH HHS/United States ; U01 HL146203/HL/NHLBI NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; P30 AI050410/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Alzheimer Disease ; *HIV Infections ; Microfluidics ; Pandemics ; *Extracellular Vesicles ; }, abstract = {Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.}, } @article {pmid38612629, year = {2024}, author = {Chagas, LDS and Serfaty, CA}, title = {The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond.}, journal = {International journal of molecular sciences}, volume = {25}, number = {7}, pages = {}, pmid = {38612629}, issn = {1422-0067}, support = {E-26/201.004/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; }, mesh = {Adult ; Child ; Humans ; *Microglia ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Neuronal Plasticity ; Brain ; Disease Progression ; Cognition ; }, abstract = {Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.}, } @article {pmid38611659, year = {2024}, author = {Werner, CR and Fusco, S and Kienzle, K and Döbele, S and Artzner, K and Malek, NP and Wichmann, D and Göpel, S}, title = {Incidence of Secondary Sclerosing Cholangitis in Hospitalized Long COVID-19 Patients: A Retrospective Single Center Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611659}, issn = {2075-4418}, abstract = {BACKGROUND: SARS-CoV-2 infection and associated COVID-19 disease can lead to critical illness with a risk of developing a multiple organ failure. Subsequently, this may lead to various pathological sequelae, such as secondary sclerosing cholangitis after surviving COVID-19 (SSC-COVID).

OBJECTIVE: The aim is to retrospectively analyze a cohort of hospitalized patients with first-wave (February 2020-June 2020) SARS-CoV-2 infection and persisting unclear cholangiopathy to determine the incidence of SSC-COVID and its risk factors.

RESULTS: A total of 249 patients were hospitalized at the university hospital in Tübingen, Germany, with SARS-CoV-2 infection during the first wave of the pandemic. Of these, 35.3% (88/249) required intensive care treatment; 16.5% (41/249) of them died due to the complications of COVID-19; 30.8% (64/208) of surviving patients could be followed up und were retrospectively analyzed at our center. The incidence of confirmed SSC-COVID was 7.8% (5/64). All SSC-COVID patients had an ICU stay >20 days, for invasive ventilation, positioning treatment, vasopressor treatment, but possible risk factors for SSC were not significant due to the small number of patients.

CONCLUSIONS: SSC-COVID is an emerging disease in post-COVID patients with a high incidence in our single-center cohort. SSC-COVID should be considered as a differential diagnosis, if unclear cholangiopathy or cholestasis persists after SARS-CoV-2 infection.}, } @article {pmid38611624, year = {2024}, author = {Makhluf, H and Madany, H and Kim, K}, title = {Long COVID: Long-Term Impact of SARS-CoV2.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611624}, issn = {2075-4418}, abstract = {Four years post-pandemic, SARS-CoV-2 continues to affect many lives across the globe. An estimated 65 million people suffer from long COVID, a term used to encapsulate the post-acute sequelae of SARS-CoV-2 infections that affect multiple organ systems. Known symptoms include chronic fatigue syndrome, brain fog, cardiovascular issues, autoimmunity, dysautonomia, and clotting due to inflammation. Herein, we review long COVID symptoms, the proposed theories behind the pathology, diagnostics, treatments, and the clinical trials underway to explore treatments for viral persistence, autonomic and cognitive dysfunctions, sleep disturbances, fatigue, and exercise intolerance.}, } @article {pmid38610673, year = {2024}, author = {Sivan, M and Smith, AB and Osborne, T and Goodwin, M and Lawrence, RR and Baley, S and Williams, P and Lee, C and Davies, H and Balasundaram, K and Greenwood, DC and , }, title = {Long COVID Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation.}, journal = {Journal of clinical medicine}, volume = {13}, number = {7}, pages = {}, pmid = {38610673}, issn = {2077-0383}, support = {COV-LT2-0016//National Institute for Health Research/ ; }, abstract = {Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC.}, } @article {pmid38610176, year = {2024}, author = {Moro-López-Menchero, P and Martín-Sanz, MB and Fernandez-de-Las-Peñas, C and Gómez-Sanchez, SM and Gil-Crujera, A and Ceballos-García, L and Escribano-Mediavilla, NI and Fuentes-Fuentes, MV and Palacios-Ceña, D}, title = {Living and Coping with Olfactory and Taste Disorders: A Qualitative Study of People with Long-COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {38610176}, issn = {2227-9032}, support = {2020/00326/001//European Regional Development Fund (FEDER), REACT-495 EU Resources of the Madrid Operational Programme 2014-2020/ ; }, abstract = {Taste and smell disorders are common symptoms of SARS-CoV-2 acute infection. In post-COVID-19 condition, symptoms can persist leading to disruption in patients' lives, to changes in their coping skills, and to the need to develop strategies for everyday life. This study aimed to describe the perspective of a group of patients with Long-COVID-19, a condition where loss of taste and/or smell was the most predominant symptom. A qualitative descriptive study was conducted. Participants who had suffered SARS-CoV-2 infection and had Long-COVID-19 loss of taste and/or smell were recruited. Purposive sampling was applied, and participants were recruited until data redundancy was reached. In-depth interviews were used for data collection and thematic analysis was applied. Twelve COVID-19 survivors (75% women) were recruited. The mean age of the participants was 55 years, and the mean duration of post-COVID-19 symptoms was 25 months. Three themes were identified: (a) Living with taste and smell disorders, describing the disorders they experience on a daily basis, how their life has changed and the accompanying emotions, (b) Changes and challenges resulting from the loss of taste and smell, changes in habits, self-care and risk in certain jobs or daily activities, (c) Coping with taste and smell disorders, describing the daily strategies used and the health care received. In conclusion, Long-COVID-19 taste and/or smell disorders limit daily life and involve changes in habits, meal preparation, and the ability to detect potentially dangerous situations.}, } @article {pmid38610152, year = {2024}, author = {Manhas, KP and Horlick, S and Krysa, J and Kovacs Burns, K and Brehon, K and Laur, C and Papathanassoglou, E and Ho, C}, title = {Implementation of a Provincial Long COVID Care Pathway in Alberta, Canada: Provider Perceptions.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {38610152}, issn = {2227-9032}, support = {Emerging COVID-19 Research Gaps and Priorities/CAPMC/CIHR/Canada ; }, abstract = {A novel, complex chronic condition emerged from the COVID-19 pandemic: long COVID. The persistent long COVID symptoms can be multisystem and varied. Effective long COVID management requires multidisciplinary, collaborative models of care, which continue to be developed and refined. Alberta's provincial health system developed a novel long COVID pathway. We aimed to clarify the perspectives of multidisciplinary healthcare providers on the early implementation of the provincial long COVID pathway, particularly pathway acceptability, adoption, feasibility, and fidelity using Sandelowki's qualitative description. Provider participants were recruited from eight early-user sites from across the care continuum. Sites represented primary care (n = 4), outpatient rehabilitation (n = 3), and COVID-19 specialty clinics (n = 2). Participants participated in structured or semi-structured virtual interviews (both group and 1:1 were available). Structured interviews sought to clarify context, processes, and pathway use; semi-structured interviews targeted provider perceptions of pathway implementation, including barriers and facilitators. Analysis was guided by Hsieh and Shannon as well as Sandelowski. Across the eight sites that participated, five structured interviews (n = 13 participants) and seven semi-structured interviews (n = 15 participants) were completed. Sites represented primary care (n = 4), outpatient rehabilitation (n = 3), and COVID-19 specialty clinics (n = 2). Qualitative content analysis was used on transcripts and field notes. Provider perceptions of the early implementation outcomes of the provincial long COVID pathway revealed three key themes: process perceptions; awareness of patient educational resources; and challenges of evolving knowledge.}, } @article {pmid38609482, year = {2024}, author = {Diexer, S and Klee, B and Gottschick, C and Broda, A and Purschke, O and Binder, M and Gekle, M and Girndt, M and Hoell, JI and Moor, I and Sedding, D and Rosendahl, J and Mikolajczyk, R}, title = {Insights into early recovery from Long COVID-results from the German DigiHero Cohort.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {8569}, pmid = {38609482}, issn = {2045-2322}, mesh = {Male ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Principal Component Analysis ; }, abstract = {65 million people worldwide are estimated to suffer from long-term symptoms after their SARS-CoV-2 infection (Long COVID). However, there is still little information about the early recovery among those who initially developed Long COVID, i.e. had symptoms 4-12 weeks after infection but no symptoms after 12 weeks. We aimed to identify associated factors with this early recovery. We used data from SARS-CoV-2-infected individuals from the DigiHero study. Participants provided information about their SARS-CoV-2 infections and symptoms at the time of infection, 4-12 weeks, and more than 12 weeks post-infection. We performed multivariable logistic regression to identify factors associated with early recovery from Long COVID and principal component analysis (PCA) to identify groups among symptoms. 5098 participants reported symptoms at 4-12 weeks after their SARS-CoV-2 infection, of which 2441 (48%) reported no symptoms after 12 weeks. Men, younger participants, individuals with mild course of acute infection, individuals infected with the Omicron variant, and individuals who did not seek medical care in the 4-12 week period after infection had a higher chance of early recovery. In the PCA, we identified four distinct symptom groups. Our results indicate differential risk of continuing symptoms among individuals who developed Long COVID. The identified risk factors are similar to those for the development of Long COVID, so people with these characteristics are at higher risk not only for developing Long COVID, but also for longer persistence of symptoms. Those who sought medical help were also more likely to have persistent symptoms.}, } @article {pmid38609036, year = {2024}, author = {Slurink, IAL and van den Houdt, SCM and Mertens, G}, title = {Who develops long COVID? Longitudinal pre-pandemic predictors of long COVID and symptom clusters in a representative Dutch population.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {144}, number = {}, pages = {107048}, doi = {10.1016/j.ijid.2024.107048}, pmid = {38609036}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology/psychology ; Male ; Female ; Middle Aged ; Netherlands/epidemiology ; Adult ; Risk Factors ; *SARS-CoV-2 ; Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Longitudinal Studies ; Cluster Analysis ; Severity of Illness Index ; Young Adult ; }, abstract = {OBJECTIVES: Prior studies show that long COVID has a heterogeneous presentation. Whether specific risk factors are related to subclusters of long COVID remains unknown. This study aimed to determine pre-pandemic predictors of long COVID and symptom clustering.

METHODS: A total of 3,022 participants of a panel representative of the Dutch population completed an online survey about long COVID symptoms. Data was merged into 2018/2019 panel data covering sociodemographic, medical, and psychosocial predictors. A total of 415 participants were classified as having long COVID. K-means clustering was used to identify patient clusters. Multivariate and lasso regression was used to identify relevant predictors compared to a COVID-19 positive control group.

RESULTS: Predictors of long-term COVID included older age, Western ethnicity, BMI, chronic disease, COVID-19 reinfections, severity, and symptoms, lower self-esteem, and higher positive affect (AUC = 0.79, 95%CI 0.73-0.86). Four clusters were identified: a low and a high symptom severity cluster, a smell-taste and respiratory symptoms cluster, and a neuro-cognitive, psychosocial, and inflammatory symptom cluster. Predictors for the different clusters included regular health complaints, healthcare use, fear of COVID-19, anxiety, depressive symptoms, and neuroticism.

CONCLUSIONS: A combination of sociodemographic, medical, and psychosocial factors predicted long COVID. Heterogenous symptom clusters suggest that there are different phenotypes of long COVID-19 presentation.}, } @article {pmid38608765, year = {2024}, author = {Rafieian, M and Skokauskas, N and Cheslack-Postava, K and Hoven, CW}, title = {The association between intolerance of uncertainty and depressive symptoms during COVID-19 in New York, USA.}, journal = {Journal of affective disorders}, volume = {356}, number = {}, pages = {628-638}, doi = {10.1016/j.jad.2024.04.037}, pmid = {38608765}, issn = {1573-2517}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Uncertainty ; Male ; Female ; *Depression/epidemiology/psychology ; Adolescent ; Adult ; *SARS-CoV-2 ; New York/epidemiology ; Child ; Young Adult ; Middle Aged ; Prevalence ; Surveys and Questionnaires ; Cohort Studies ; }, abstract = {BACKGROUND: Coronavirus Disease 2019 (COVID-19), a highly contagious respiratory illnesses, has globally impacted mental health. This study aims to investigate the association between intolerance of uncertainty and depressive symptoms during the pandemic in New York, USA, considering COVID-19-related worries as modifiers and mediators.

METHOD: 1227 participants from three ongoing cohort studies, originally centered on trauma-exposed children and adolescents, provided data via questionnaires and telephone interviews across three waves. We used multivariable logistic and linear regression models to investigate the intolerance of uncertainty-depressive symptoms relationship, while adjusting for potential confounders and assessing the modification and mediation effects of Covid-19 related worries.

RESULTS: Depressive symptoms prevalence was 18 %, 12 %, and 9 % at waves 0, 1, and 2 respectively. Strong positive associations were observed between intolerance of uncertainty above the median and depressive symptoms which remained significant after adjusting for potential confounders. Odds ratios were 2.14 (95 % CI: 1.54-2.99) and 4.50 (95 % CI: 2.67-7.93) for intolerance of uncertainty-depressive symptoms association at wave 0 and 1 respectively, and 3.22 (95 % CI: 1.68-6.63) for intolerance of uncertainty at wave 1 and depressive symptoms at wave 2. There was evidence of partial mediation by worries (12-37 %), but no evidence of a moderating effect.

LIMITATION: It includes study's methodology, including self-report measures, remote data collection, and uncontrolled variables like anxiety and COVID-19 perspectives.

CONCLUSION: The findings emphasize the importance of evidence-based strategies for tackling intolerance of uncertainty during pandemics, particularly in managing long COVID. Collaborative efforts between policymakers and clinicians are essential in this endeavor.}, } @article {pmid38608516, year = {2024}, author = {Hadidchi, R and Wang, SH and Rezko, D and Henry, S and Coyle, PK and Duong, TQ}, title = {SARS-CoV-2 infection increases long-term multiple sclerosis disease activity and all-cause mortality in an underserved inner-city population.}, journal = {Multiple sclerosis and related disorders}, volume = {86}, number = {}, pages = {105613}, doi = {10.1016/j.msard.2024.105613}, pmid = {38608516}, issn = {2211-0356}, mesh = {Humans ; *COVID-19/mortality/complications/epidemiology ; Male ; Female ; Middle Aged ; *Multiple Sclerosis/mortality/epidemiology/drug therapy ; Retrospective Studies ; Adult ; Comorbidity ; Optic Neuritis/epidemiology ; Urban Population/statistics & numerical data ; Hospitalization/statistics & numerical data ; New York City/epidemiology ; }, abstract = {BACKGROUND: Although certain subsets patients with multiple sclerosis (MS), an immune-mediated disorder, are at higher risk of worse acute COVID-19 outcomes compared to the general population, it is not clear whether SARS-CoV-2 infection impacts long-term outcomes compared with MS patients without COVID-19 infection.

OBJECTIVES: This study investigated MS disease activity and mortality 3.5 years post SARS-CoV-2 infection and compared with MS patients without COVID-19.

METHODS: This retrospective study evaluated 1,633 patients with MS in the Montefiore Health System in the Bronx from January 2016 to July 2023. This health system serves a large minority population and was an epicenter for the early pandemic and subsequent surges of infection. Positive SARS-CoV-2 infection was determined by a positive polymerase-chain-reaction test. Primary outcomes were all-cause mortality, and optic neuritis post SARS-CoV-2 infection. Secondary outcomes included change in disease-modifying therapy (DMT), treatment with high-dose methylprednisolone, cerebellar deficits, relapse, and all-cause hospitalization post-infection.

RESULTS: MS patients with COVID-19 had similar demographics but higher prevalence of pre-existing major comorbidities (hypertension, type-2 diabetes, chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and coronary artery disease), optic neuritis, and history of high dose steroid treatment for relapses compared to MS patients without COVID-19. MS patients with COVID-19 had greater risk of mortality (adjusted HR=4.34[1.67, 11.30], p < 0.005), greater risk of post infection optic neuritis (adjusted HR=2.97[1.58, 5.58], p < 0.005), higher incidence of methylprednisolone treatment for post infection acute relapse (12.65% vs. 2.54 %, p < 0.001), and more hospitalization (78.92% vs. 66.81 %, p < 0.01), compared to MS patients without COVID-19.

CONCLUSIONS: MS patients who survived COVID-19 infection experienced worse long-term outcomes, as measured by treatment for relapse, hospitalization and mortality. Identifying risk factors for worse long-term outcomes may draw clinical attention to the need for careful follow-up of at-risk individuals post-SARS-CoV-2 infection.}, } @article {pmid38608263, year = {2024}, author = {Dorronzoro-Zubiete, E and Castro-Marrero, J and Ropero, J and Sevillano-Ramos, JL and Dolores Hernández, M and Sanmartin Sentañes, R and Alegre-Martin, J and Launois-Obregón, P and Martin-Garrido, I and Luque Budia, A and Lacalle-Remigio, JR and Béjar Prado, L and Rivera Romero, O}, title = {Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e50157}, pmid = {38608263}, issn = {1929-0748}, abstract = {BACKGROUND: Fatigue is the most common symptom in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, impacting patients' quality of life; however, there is currently a lack of evidence-based context-aware tools for fatigue self-management in these populations.

OBJECTIVE: This study aimed to (1) address fatigue in ME/CFS and long COVID through the development of digital mobile health solutions for self-management, (2) predict perceived fatigue severity using real-time data, and (3) assess the feasibility and potential benefits of personalized digital mobile health solutions.

METHODS: The MyFatigue project adopts a patient-centered approach within the participatory health informatics domain. Patient representatives will be actively involved in decision-making processes. This study combines inductive and deductive research approaches, using qualitative studies to generate new knowledge and quantitative methods to test hypotheses regarding the relationship between factors like physical activity, sleep behaviors, and perceived fatigue in ME/CFS and long COVID. Co-design methods will be used to develop a personalized digital solution for fatigue self-management based on the generated knowledge. Finally, a pilot study will evaluate the feasibility, acceptance, and potential benefits of the digital health solution.

RESULTS: The MyFatigue project opened to enrollment in November 2023. Initial results are expected to be published by the end of 2024.

CONCLUSIONS: This study protocol holds the potential to expand understanding, create personalized self-management approaches, engage stakeholders, and ultimately improve the well-being of individuals with ME/CFS and long COVID.

PRR1-10.2196/50157.}, } @article {pmid38607618, year = {2024}, author = {Harris, E}, title = {Trials Will Evaluate Treatments for Long COVID Nervous System Problems.}, journal = {JAMA}, volume = {331}, number = {17}, pages = {1439-1440}, doi = {10.1001/jama.2024.5156}, pmid = {38607618}, issn = {1538-3598}, mesh = {Humans ; Anti-Infective Agents/therapeutic use ; Cardiovascular Agents/therapeutic use ; Clinical Trials as Topic ; COVID-19/complications/therapy ; COVID-19 Drug Treatment ; Immunoglobulins, Intravenous/therapeutic use ; Ivabradine/therapeutic use ; Nervous System Diseases/etiology/therapy ; *Post-Acute COVID-19 Syndrome/etiology/therapy ; *Postural Orthostatic Tachycardia Syndrome/etiology/therapy ; }, } @article {pmid38607581, year = {2024}, author = {Elfessi, ZZ and Gardner, J and Gordon, HS and Rubinstein, I}, title = {Long COVID in Women Veterans Residing in Underserved, Socioeconomically Disadvantaged Neighborhoods of Chicago.}, journal = {Population health management}, volume = {27}, number = {3}, pages = {227-230}, doi = {10.1089/pop.2024.0039}, pmid = {38607581}, issn = {1942-7905}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Chicago/epidemiology ; *Veterans/statistics & numerical data ; *Vulnerable Populations ; Middle Aged ; Aged ; SARS-CoV-2 ; Residence Characteristics ; Adult ; }, } @article {pmid38607276, year = {2024}, author = {Gaudreau-Majeau, F and Gagnon, C and Djedaa, SC and Bérubé, B and Malo, J and Iglesies-Grau, J and Gayda, M and Bherer, L and Besnier, F}, title = {Cardiopulmonary rehabilitation's influence on cognitive functions, psychological state, and sleep quality in long COVID-19 patients: A randomized controlled trial.}, journal = {Neuropsychological rehabilitation}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/09602011.2024.2338613}, pmid = {38607276}, issn = {1464-0694}, abstract = {NCT05035628.Trial registration: ClinicalTrials.gov identifier: NCT05035628..}, } @article {pmid38605630, year = {2024}, author = {Le, GH and Kwan, ATH and Guo, Z and Wong, S and Badulescu, S and Gill, H and Teopiz, KM and Meshkat, S and Ceban, F and Phan, L and Subramaniapillai, M and Di Vincenzo, JD and Rosenblat, JD and Mansur, RB and d'Andrea, G and Ho, R and Rhee, TG and McIntyre, RS}, title = {Impact of elevated body mass index (BMI) on cognitive functioning and inflammation in persons with post-COVID-19 condition: a secondary analysis.}, journal = {Acta neuropsychiatrica}, volume = {36}, number = {4}, pages = {211-217}, doi = {10.1017/neu.2024.16}, pmid = {38605630}, issn = {1601-5215}, mesh = {Humans ; *Body Mass Index ; Male ; Female ; *COVID-19/complications ; *Inflammation/blood ; Middle Aged ; Double-Blind Method ; *Cognitive Dysfunction/etiology ; *Obesity/complications/psychology ; Adult ; C-Reactive Protein/metabolism/analysis ; Cognition/drug effects ; Aged ; Post-Acute COVID-19 Syndrome ; Neuropsychological Tests ; Blood Sedimentation ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterised by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC.

METHODS: This is a post-hoc analysis of a randomised, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impact of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

RESULTS: Complete data from 70 participants were statistically analysed and adjusted for age and sex. BMI was negatively correlated with performance on the DSST (β = -0.003, p = 0.047), TMT-A (β = -0.006, p = 0.025), and TMT-B (β = -0.006, p = 0.002). BMI was positively correlated with serum CRP (unstandardized β = 0.193, standardized β = 0.612, p < 0.001) and ESR (β = 0.039, p < 0.001) levels.

CONCLUSION: We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.}, } @article {pmid38605121, year = {2024}, author = {Angulo-Aguado, M and Carrillo-Martinez, JC and Contreras-Bravo, NC and Morel, A and Parra-Abaunza, K and Usaquén, W and Fonseca-Mendoza, DJ and Ortega-Recalde, O}, title = {Next-generation sequencing of host genetics risk factors associated with COVID-19 severity and long-COVID in Colombian population.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {8497}, pmid = {38605121}, issn = {2045-2322}, support = {QAN-BG277//Hospital Universitario Mayor - Méderi/ ; QAN-BG277//Hospital Universitario Mayor - Méderi/ ; ABN062//Universidad del Rosario/ ; ABN062//Universidad del Rosario/ ; }, mesh = {Male ; Humans ; *COVID-19/epidemiology/genetics ; Colombia/epidemiology ; Post-Acute COVID-19 Syndrome ; High-Throughput Nucleotide Sequencing ; Risk Factors ; }, abstract = {Coronavirus disease 2019 (COVID-19) was considered a major public health burden worldwide. Multiple studies have shown that susceptibility to severe infections and the development of long-term symptoms is significantly influenced by viral and host factors. These findings have highlighted the potential of host genetic markers to identify high-risk individuals and develop target interventions to reduce morbimortality. Despite its importance, genetic host factors remain largely understudied in Latin-American populations. Using a case-control design and a custom next-generation sequencing (NGS) panel encompassing 81 genetic variants and 74 genes previously associated with COVID-19 severity and long-COVID, we analyzed 56 individuals with asymptomatic or mild COVID-19 and 56 severe and critical cases. In agreement with previous studies, our results support the association between several clinical variables, including male sex, obesity and common symptoms like cough and dyspnea, and severe COVID-19. Remarkably, thirteen genetic variants showed an association with COVID-19 severity. Among these variants, rs11385942 (p < 0.01; OR = 10.88; 95% CI = 1.36-86.51) located in the LZTFL1 gene, and rs35775079 (p = 0.02; OR = 8.53; 95% CI = 1.05-69.45) located in CCR3 showed the strongest associations. Various respiratory and systemic symptoms, along with the rs8178521 variant (p < 0.01; OR = 2.51; 95% CI = 1.27-4.94) in the IL10RB gene, were significantly associated with the presence of long-COVID. The results of the predictive model comparison showed that the mixed model, which incorporates genetic and non-genetic variables, outperforms clinical and genetic models. To our knowledge, this is the first study in Colombia and Latin-America proposing a predictive model for COVID-19 severity and long-COVID based on genomic analysis. Our study highlights the usefulness of genomic approaches to studying host genetic risk factors in specific populations. The methodology used allowed us to validate several genetic variants previously associated with COVID-19 severity and long-COVID. Finally, the integrated model illustrates the importance of considering genetic factors in precision medicine of infectious diseases.}, } @article {pmid38605011, year = {2024}, author = {Jiao, T and Huang, Y and Sun, H and Yang, L}, title = {Research progress of post-acute sequelae after SARS-CoV-2 infection.}, journal = {Cell death & disease}, volume = {15}, number = {4}, pages = {257}, pmid = {38605011}, issn = {2041-4889}, support = {81970663//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Disease Progression ; }, abstract = {SARS-CoV-2 has spread rapidly worldwide and infected hundreds of millions of people worldwide. With the increasing number of COVID-19 patients discharged from hospitals, the emergence of its associated complications, sequelae, has become a new global health crisis secondary to acute infection. For the time being, such complications and sequelae are collectively called "Post-acute sequelae after SARS-CoV-2 infection (PASC)", also referred to as "long COVID" syndrome. Similar to the acute infection period of COVID-19, there is also heterogeneity in PASC. This article reviews the various long-term complications and sequelae observed in multiple organ systems caused by COVID-19, pathophysiological mechanisms, diagnosis, and treatment of PASC, aiming to raise awareness of PASC and optimize management strategies.}, } @article {pmid38603493, year = {2024}, author = {Couzin-Frankel, J}, title = {Lessons in persistence.}, journal = {Science (New York, N.Y.)}, volume = {384}, number = {6692}, pages = {150-154}, doi = {10.1126/science.adp7205}, pmid = {38603493}, issn = {1095-9203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/therapy/virology ; *SARS-CoV-2 ; Clinical Trials as Topic ; }, abstract = {New Long Covid trials aim to clear lingering virus-and help patients in dire need.}, } @article {pmid38601833, year = {2024}, author = {Massoumi, LE and Rosenbaum, A}, title = {Case Report on High Dose Lithium Treatment for Post-COVID Depression, Recurrent Fevers, and Skin Lesions.}, journal = {Psychopharmacology bulletin}, volume = {54}, number = {2}, pages = {39-45}, pmid = {38601833}, issn = {2472-2448}, mesh = {Female ; Humans ; Adult ; *Lithium/therapeutic use ; Depression ; *COVID-19 ; Lithium Compounds/therapeutic use ; }, abstract = {This is a case of a 35-year-old woman who presented with an 18-month history of post (long)-COVID depression and exhaustion along with recurrent fevers and treatment-resistant skin boils, all of which abated with lithium treatment at a serum level of 1.14 mmol/L, and all of which worsened when the lithium serum level was lowered to 0.8. This paper illustrates Lithium's effectiveness in the treatment of post (long)-COVID syndrome, though a higher serum concentration may be required.}, } @article {pmid38601317, year = {2024}, author = {Silva, MGS and Carvalho, TL and de Azevedo Vieira, JE and da Costa, LR and da Silva, DLO and Costa, ALB and Dos Anjos, HPS and Lopes, AJ}, title = {Evaluating performance on the Glittre-ADL test in men with long COVID 3 years after a SARS-CoV-2 infection.}, journal = {Journal of exercise science and fitness}, volume = {22}, number = {4}, pages = {271-277}, pmid = {38601317}, issn = {1728-869X}, abstract = {BACKGROUND/OBJECTIVE: Many COVID-19 survivors, especially those who have been hospitalized, have been suffering numerous complications that limit their activities of daily living, although changes that persist 3 years after infection are still not known. We aimed to investigate the impact of long COVID on the Glittre-ADL test (TGlittre) 3 years after acute infection in men who needed hospitalization and explore whether the performance on the TGlittre is associated with impairments in lung function, muscle strength, physical function and quality of life (QoL).

METHODS: Cross-sectional study with 42 men with long COVID who took the TGlittre. They underwent pulmonary function tests and measurements of handgrip strength and quadriceps strength (QS). Additionally, they also completed the Saint George Respiratory Questionnaire (SGRQ) and Functional Independence Measure (FIM).

RESULTS: The mean age was 52 ± 10.6 years, while the mean time after diagnosis of COVID-19 was 37 ± 3.5 months. The mean TGlittre time was 3.3 (3.1-4.1) min, which was 10% greater than the time expected for normal individuals to complete it. The TGlittre time was correlated significantly with the QS (rs = -0.397, p = 0.009), pulmonary diffusion (rs = - 0.364, p = 0.017), FIM (rs = -0.364, p = 0.017) and the "activity" domain score of the SGRQ (rs = 0.327, p = 0.034).

CONCLUSION: Functional capacity on exertion as measured by the TGlittre time is normal in most men with long COVID 3 years after hospitalization. However, this improvement in functional capacity does not seem to be reflected in muscle strength or QoL, requiring continued monitoring even after 3 years.}, } @article {pmid38600563, year = {2024}, author = {Domingo, JC and Battistini, F and Cordobilla, B and Zaragozá, MC and Sanmartin-Sentañes, R and Alegre-Martin, J and Cambras, T and Castro-Marrero, J}, title = {Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {343}, pmid = {38600563}, issn = {1479-5876}, support = {PI19/00731//Instituto de Salud Carlos III/ ; PI19/00629//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Pilot Projects ; Prospective Studies ; *COVID-19 ; Cohort Studies ; Patient Acuity ; Biomarkers ; Inflammation ; }, abstract = {BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions.

METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses.

RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2[-] + NO3[-]) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1β (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population.

CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.}, } @article {pmid38599706, year = {2024}, author = {Escaned, J and Espejo-Paeres, C and Jerónimo, A and Travieso, A and Chipayo-Gonzales, D and Nuñez-Gil, I and Capote, ML and Gonzalo, N and Mejía-Rentería, H}, title = {Myocardial Ischemia of Nonobstructive Origin as a Cause of New-Onset Chest Pain in Long-COVID Syndrome.}, journal = {JACC. Cardiovascular interventions}, volume = {17}, number = {7}, pages = {958-960}, doi = {10.1016/j.jcin.2024.01.072}, pmid = {38599706}, issn = {1876-7605}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Treatment Outcome ; *Coronary Artery Disease/complications ; *Myocardial Ischemia/complications/diagnostic imaging ; Chest Pain/etiology ; }, } @article {pmid38596549, year = {2023}, author = {Radkhah, H and Omidali, M and Hejrati, A and Bahri, RA and Arefi, S and Behzadi, A and Eslami, M and Khadembashiri, M and Khadembashiri, M and Najafirashed, M and Amiri, BS}, title = {Correlations of Long COVID Symptoms and Inflammatory Markers of Complete Blood Count (CBC): A Cross-sectional Study.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {13}, number = {6}, pages = {112-119}, pmid = {38596549}, issn = {2000-9666}, abstract = {BACKGROUND: Long-COVID refers to lasting unspecific symptoms like fatigue, decreased concentration and sleep issues after infection which persist for at least three months and cannot be attributed to other causes. Previous studies surveyed the association between inflammatory markers like C - reactive protein (CRP) at hospital admission and long-COVID symptoms in the preceding months. Post-COVID syndrome can affect one-third of patients. Thus early diagnosis can assist in reducing burdens on public health. We attempted to see any correlations between complete blood count (CBC) markers (like red blood cell (RBC), white blood cell (WBC), Neutrophil to lymphocyte ratio (NLR), etc.) at hospital admission and long COVID symptoms at a 6-month follow-up.

METHODS: 167 patients (44.9% females, mean age 49 years old) answered semi-structural interviews through telemedicine which focused on the three prominent symptoms: fatigue, loss of concentration and decreased libido. Results: Two third of patients have symptoms of long COVID and others do not have. NLR in the symptomatic group was statically higher. Patients who underwent decreased libido at a 6-month follow-up had significantly more severe lymphopenia (p = 0.028) and higher NLR values (p-value = 0.007). Poor mental concentration is associated with high WBC in numbers and polymorphonuclear (PMN) count. Other symptoms do not correlate with blood markers.

CONCLUSION: Utilizing available data like CBC can help predict the upcoming symptoms of previously hospitalized patients and further measures like rehabilitation. Additional investigations should be done on the effect of COVID vaccination on converting long COVID. Different variants of the virus may have different results.}, } @article {pmid38596351, year = {2024}, author = {Barilaite, E and Watson, H and Hocaoglu, MB}, title = {Understanding Patient-Reported Outcome Measures Used in Adult Survivors Experiencing Long-Term Effects After COVID-19 Infection: A Rapid Review.}, journal = {Journal of patient-centered research and reviews}, volume = {11}, number = {1}, pages = {36-50}, pmid = {38596351}, issn = {2330-0698}, abstract = {PURPOSE: Patient-reported outcome measures (PROMs) are used in individuals experiencing long-term effects from COVID-19 infection, or Long COVID, to evaluate the quality of life and functional status of these individuals. However, little is known about which PROMs are being utilised and the psychometric properties of these PROMs. Our purpose was thus to explore which PROMs are used in Long COVID patients and to discuss the psychometric properties of the PROMs.

METHODS: For this rapid review, a systematic literature search was performed in the PubMed, Embase, and CINAHL databases. The found studies were screened using the PRISMA flowchart. We then performed study quality appraisal and assessed the psychometric properties of the found PROMs.

RESULTS: Per the systematic literature search and after removal of duplicates, 157 publications were identified for individual screening. After screening and eligibility assessment, 74 articles were selected for our review. In total, 74 PROMs were used and primarily comprised quality of life, fatigue, breathlessness, mental health, and smell/taste issues in COVID "long haulers." Five studies used newly developed, COVID-19-specific PROMs. We assessed the psychometric properties of the 10 most-used PROMs. The majority were found to be reliable and valid instruments. EQ-5D-5L was the most popular and highly rated PROM.

CONCLUSIONS: We assessed PROMs used in Long COVID patients and evaluated their psychometric properties. EQ-5D-5L was the most favourably rated PROM. PROMs addressing mental health issues are crucial in managing anxiety and depression in Long COVID patients. New COVID-specific PROMs assess functional status and smell/taste perception and show great utilisation potential in olfactory training at COVID smell clinics. However, many reviewed PROMs currently lack sufficient analysis of their psychometric properties. Therefore, future research needs to examine these measures.}, } @article {pmid38596000, year = {2024}, author = {Arêas, GPT and Goulart, CDL and Sant'Anna, T and Fernandes, TG and Alvim, RO and Borges, FFDR and do Amaral, CMSSB and Rodrigues, SCF and Valente, J and Ferreira, JMBB and Rezende, AG and de Oliveira Júnior, EF and de Lacerda, MVG and de Almeida-Val, FF}, title = {Pulmonary Rehabilitation Associated with Noninvasive Ventilation on Physical Capacity and Quality of Life in Post-COVID-19: A Randomized Controlled Double-Blinded Clinical Trial Protocol.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {1483-1490}, pmid = {38596000}, issn = {1178-2390}, abstract = {BACKGROUND: The coronavirus disease-2019 (COVID-19) pulmonary rehabilitation (PR) seems to be a better choice to improve physical and functional capacity after acute infection. However, there is a lack of evidence regarding the effects of different strategies to optimize post-acute phase rehabilitation and reduce long COVID-19 physical deteriorations.

OBJECTIVE: To compare the use of a noninvasive ventilation (NIV) plus aerobic exercise strategy during PR program with to a standard PR (without NIV) on physical capacity and quality of life outcomes in post-COVID-19.

METHODS: Double-blinded randomized controlled clinical trial. A total of 100 individuals discharged from hospital in a post-acute phase of severe COVID-19 will be randomized into two groups: PR + NIV (Group 1) and PR (Group 2). Inclusion criteria include participants who present symptomatic dyspnea II and III by the modified Medical Research Council, aged 18 years or older. Both groups will receive aerobic and resistance exercise, and inspiratory muscle training. However, group 1 will perform aerobic training with bilevel NIV. Cardiopulmonary exercise test will assess the O2 peak uptake, 6-minute walk test will assess the walking distance and short-form 36 will assess the quality of life before and after 8 weeks (after 24 PR sessions). Moreover, patients will be contacted by telephone every 3 months for one year to record possible adverse events, hospitalizations, and death. All data will be registered in RedCap, and analyses will be performed in the STATA v13 software.

CLINICAL TRIAL REGISTRATION: RBR-3t9pkzt.}, } @article {pmid38593796, year = {2024}, author = {Cooper, L and Xu, H and Polmear, J and Kealy, L and Szeto, C and Pang, ES and Gupta, M and Kirn, A and Taylor, JJ and Jackson, KJL and Broomfield, BJ and Nguyen, A and Gago da Graça, C and La Gruta, N and Utzschneider, DT and Groom, JR and Martelotto, L and Parish, IA and O'Keeffe, M and Scharer, CD and Gras, S and Good-Jacobson, KL}, title = {Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.}, journal = {Immunity}, volume = {57}, number = {5}, pages = {1037-1055.e6}, pmid = {38593796}, issn = {1097-4180}, support = {R01 AI148471/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Interferon Type I/metabolism/immunology ; *Lymphocytic Choriomeningitis/immunology/virology ; Mice ; *Lymphocytic choriomeningitis virus/immunology ; *Memory B Cells/immunology ; *Epigenesis, Genetic ; Mice, Inbred C57BL ; Receptor, Interferon alpha-beta/genetics ; Immunologic Memory/immunology ; Chronic Disease ; B-Lymphocyte Subsets/immunology ; Single-Cell Analysis ; }, abstract = {Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet[+] subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c[+]CD80[+] cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post-infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.}, } @article {pmid38593220, year = {2024}, author = {Durstenfeld, MS and Weiman, S and Holtzman, M and Blish, C and Pretorius, R and Deeks, SG}, title = {Long COVID and post-acute sequelae of SARS-CoV-2 pathogenesis and treatment: A Keystone Symposia report.}, journal = {Annals of the New York Academy of Sciences}, volume = {1535}, number = {1}, pages = {31-41}, pmid = {38593220}, issn = {1749-6632}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; R35 HL145242/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/therapy/complications/virology ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2/pathogenicity ; COVID-19 Drug Treatment ; }, abstract = {In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post-acute sequelae of COVID-19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism-focused randomized, placebo-controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post-infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post-infectious syndromes.}, } @article {pmid38592295, year = {2024}, author = {Khodanovich, M and Naumova, A and Kamaeva, D and Obukhovskaya, V and Vasilieva, S and Schastnyy, E and Kataeva, N and Levina, A and Kudabaeva, M and Pashkevich, V and Moshkina, M and Tumentceva, Y and Svetlik, M}, title = {Neurocognitive Changes in Patients with Post-COVID Depression.}, journal = {Journal of clinical medicine}, volume = {13}, number = {5}, pages = {}, pmid = {38592295}, issn = {2077-0383}, support = {22-15-00481//Russian Science Foundation/ ; }, abstract = {Background: Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD, n = 25) patients using neuropsychological testing. Methods: The study involved 71 post-COVID patients with matched control groups: recovered COVID-19 individuals without complications (n = 18) and individuals without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, and a comparison group (noPCD, n = 46) included participants with neurological COVID-19 complications, excluding clinical depression. Results: The PCD patients showed gender-dependent significant cognitive impairment in the MoCA, Word Memory Test (WMT), Stroop task (SCWT), and Trail Making Test (TMT) compared to the controls and noPCD patients. Men with PCD showed worse performances on the SCWT, in MoCA attention score, and on the WMT (immediate and delayed word recall), while women with PCD showed a decline in MoCA total score, an increased processing time with less errors on the TMT, and worse immediate recall. No differences between groups in Sniffin's stick test were found. Conclusions: COVID-related direct (post-COVID symptoms) and depression-mediated (depression itself, male sex, and severity of COVID-19) predictors of decline in memory and information processing speed were identified. Our findings may help to personalize the treatment of depression, taking a patient's gender and severity of previous COVID-19 disease into account.}, } @article {pmid38592290, year = {2024}, author = {Sárközi, AT and Tornyi, I and Békési, E and Horváth, I}, title = {Co-Morbidity Clusters in Post-COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {13}, number = {5}, pages = {}, pmid = {38592290}, issn = {2077-0383}, abstract = {Background: Post-COVID-19 syndrome, characterized by persistent symptoms emerging more than 12 weeks after acute infection, displays diverse manifestations. This study aimed to analyze co-existing organ dysfunctions in post-COVID-19 patients and explore their potential association with the acute COVID-19 episode and functional impairment. Methods: Data from 238 patients attending post-COVID-19 outpatient care between 1 March 2021 and 1 March 2022, after previous hospitalization for acute COVID-19, were retrospectively analyzed with 80 having comprehensive mapping of organ involvement. Results: The average time between acute episode and post-COVID-19 care was 149 days. Spirometry indicated significant abnormalities in lung function. Predominant symptoms included respiratory (75%), fatigue (73%), neurological (62.5%), and ear-nose-throat issues (51.25%). Multiorgan dysfunctions were observed in 87.5% of patients, contributing to an 18.33% reduction in health quality compared to pre-acute COVID-19 levels. Subgroup analysis identified four distinct post-COVID-19 syndrome subgroups, highlighting the coexistence of respiratory and neurological disorders as potential indicators and drivers of further organ involvement. Our results reveal that most patients with post-COVID-19 syndrome suffer from multiorgan disorders. Conclusions: The presence of coexisting respiratory and neurological symptoms suggests the involvement of other organ systems as well. The complexity of multiorgan involvement requires further studies to provide insights into the different symptom clusters and identify potential targets for personalized preventive and therapeutic interventions to improve patient outcome.}, } @article {pmid38592016, year = {2024}, author = {Jangnin, R and Ritruangroj, W and Kittisupkajorn, S and Sukeiam, P and Inchai, J and Maneeton, B and Maneetorn, N and Chaiard, J and Theerakittikul, T}, title = {Long-COVID Prevalence and Its Association with Health Outcomes in the Post-Vaccine and Antiviral-Availability Era.}, journal = {Journal of clinical medicine}, volume = {13}, number = {5}, pages = {}, pmid = {38592016}, issn = {2077-0383}, support = {COV11/2565//Faculty of medicine, Chiang Mai University/ ; }, abstract = {Background and Objectives: After recovering from COVID-19, patients may experience persistent symptoms, known as post-COVID-19 syndrome or long COVID, which include a range of continuing health problems. This research explores the prevalence, associated factors, and overall health outcomes of long COVID during a period of extensive vaccination and antiviral treatment availability in Thailand. Materials and Methods: This observational study involved 390 adult patients with COVID-19 between January and March 2022. Beginning three months after their diagnosis, these patients were interviewed via telephone every three months for a period of one year. The data collection process included gathering demographic information and administering a standardized questionnaire that addressed the patients' physical condition following COVID-19, their mental health, sleep disturbances, and overall quality of life. Results: The cohort consisted of 390 participants, with an average age of 31.8 ± 13.6. Among them, 96.7% (n = 377) were vaccinated, and 98.2% (n = 383) underwent antiviral treatment. Long-COVID prevalence was observed at 77.7%, with the most frequently reported symptoms being fatigue (64.1%) and cough (43.9%). Regarding mental health, depression was reported by 8.2% of the participants, anxiety by 4.1%, and poor sleep quality by 33.3%. Advanced statistical analysis using multivariable logistic regression showed significant links between long-COVID symptoms and patients aged below 60 (p = 0.042), as well as the initial symptom of cough (p = 0.045). In the subset of long-COVID sufferers, there was a notable correlation in females with symptoms such as headaches (p = 0.001), dizziness (p = 0.007), and brain fog (p = 0.013). Conclusions: Despite the extensive distribution of vaccines and antiviral therapies, the prevalence of long COVID remains high, being associated particularly with individuals under 60 and those exhibiting a cough as an early symptom. The study further reveals that mental health issues related to long COVID are profound, going beyond the scope of physical symptomatology.}, } @article {pmid38590789, year = {2024}, author = {Kikinis, Z and Castañeyra-Perdomo, A and González-Mora, JL and Rushmore, RJ and Toppa, PH and Haggerty, K and Papadimitriou, G and Rathi, Y and Kubicki, M and Kikinis, R and Heller, C and Yeterian, E and Besteher, B and Pallanti, S and Makris, N}, title = {Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1337888}, pmid = {38590789}, issn = {1664-0640}, support = {K24 MH116366/MH/NIMH NIH HHS/United States ; R01 MH112748/MH/NIMH NIH HHS/United States ; R21 DA042271/DA/NIDA NIH HHS/United States ; R01 MH125860/MH/NIMH NIH HHS/United States ; R01 NS125307/NS/NINDS NIH HHS/United States ; R01 AG042512/AG/NIA NIH HHS/United States ; R01 MH111917/MH/NIMH NIH HHS/United States ; }, abstract = {Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.}, } @article {pmid38590093, year = {2024}, author = {Estebanez-Pérez, MJ and Martín-Valero, R and Pastora-Estebanez, P and Pastora-Bernal, JM}, title = {Experiences of people with Long Covid with a digital physiotherapy intervention: A qualitative study.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {2}, pages = {e13993}, pmid = {38590093}, issn = {1369-7625}, support = {//None/ ; }, mesh = {Humans ; *COVID-19 ; Exercise Therapy/methods ; Physical Therapy Modalities ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; Qualitative Research ; }, abstract = {PURPOSE: Long Covid syndrome is a multiorgan condition with multiple sequelae affecting quality of life, capacity to work and daily activities. The advantages that new technologies can offer are presented as an opportunity in the current healthcare framework.

OBJECTIVE: This research aimed to explore people with Long Covid's experiences with a digital physiotherapy practice intervention, during four weeks.

METHODS: Qualitative semistructured interviews were conducted by video call. Thirty-two Long Covid participants were invited to join an in-depth interview once the intervention was completed. Participants were queried on their intervention experiences and perceptions, as well as any lifestyle changes made, as a result of receiving digital physiotherapy practice. The interviews were transcribed and analysed using inductive qualitative content analysis.

RESULTS: In-depth qualitative analysis has revealed four themes that reflect participants' perceptions of digital physiotherapy intervention. The helpfulness of the exercises, interaction with the physiotherapist, the domestic use of technology and the future of digital health practice were the topics highlighted by Long Covid participants. Some improvements have been suggested including video sounds and the need to introduce face-to-face sessions. Participants stated that interventions were helpful and superior to printed exercise sheets, mobile phone apps and usual care received. This intervention did not present major barriers, highlighting the importance of personalized care and continuity in the provision of health services.

CONCLUSION: The digital physiotherapy practice is perceived by people with Long Covid as an appropriate method for the care of their health needs. Participants stated the need for this type of intervention in the public health system, where it would eliminate waiting lists, facilitate accessibility and improve existing care.

Participants contributed to the interpretation of the data acquired in the interview.

CLINICAL TRIAL REGISTRATION: Trial registration NCT04742946.}, } @article {pmid38589621, year = {2024}, author = {Liew, F and Efstathiou, C and Fontanella, S and Richardson, M and Saunders, R and Swieboda, D and Sidhu, JK and Ascough, S and Moore, SC and Mohamed, N and Nunag, J and King, C and Leavy, OC and Elneima, O and McAuley, HJC and Shikotra, A and Singapuri, A and Sereno, M and Harris, VC and Houchen-Wolloff, L and Greening, NJ and Lone, NI and Thorpe, M and Thompson, AAR and Rowland-Jones, SL and Docherty, AB and Chalmers, JD and Ho, LP and Horsley, A and Raman, B and Poinasamy, K and Marks, M and Kon, OM and Howard, LS and Wootton, DG and Quint, JK and de Silva, TI and Ho, A and Chiu, C and Harrison, EM and Greenhalf, W and Baillie, JK and Semple, MG and Turtle, L and Evans, RA and Wain, LV and Brightling, C and Thwaites, RS and Openshaw, PJM and , and , }, title = {Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.}, journal = {Nature immunology}, volume = {25}, number = {4}, pages = {607-621}, pmid = {38589621}, issn = {1529-2916}, support = {MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; MR/T50256X/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/12/MRC_/Medical Research Council/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20029/MRC_/Medical Research Council/United Kingdom ; MC_PC_20004/MRC_/Medical Research Council/United Kingdom ; MR/R005982/1/MRC_/Medical Research Council/United Kingdom ; MR/R502121/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Biomedical Research ; Hospitalization ; Immunoglobulin G ; }, abstract = {One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood[1]. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.}, } @article {pmid38589620, year = {2024}, author = {Ceglarek, L and Boyman, O}, title = {Immune dysregulation in long COVID.}, journal = {Nature immunology}, volume = {25}, number = {4}, pages = {587-589}, pmid = {38589620}, issn = {1529-2916}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38588934, year = {2024}, author = {Thapaliya, K and Marshall-Gradisnik, S and Eaton-Fitch, N and Eftekhari, Z and Inderyas, M and Barnden, L}, title = {Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.007}, pmid = {38588934}, issn = {1555-7162}, abstract = {PURPOSE: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

METHODS: Magnetic resonance spectroscopy data were acquired with a 3T Prisma magnetic resonance imaging scanner (Siemens Healthcare, Erlangen, Germany). We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n = 17), ME/CFS (n = 17), and healthy controls (n = 10) using Osprey software. The statistical analyses were performed using SPSS version 29 (IBM, Armonk, NY). Age and sex were included as nuisance covariates.

RESULTS: Glutamate levels were significantly higher in patients with long COVID (P = .02) and ME/CFS (P = .017) than in healthy controls. No significant difference was found between the 2 patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (P = .012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

CONCLUSION: Our study identified significantly elevated glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the 2 patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.}, } @article {pmid38588073, year = {2024}, author = {Stave, GM and Nabeel, I and Durand-Moreau, Q}, title = {Long COVID-ACOEM Guidance Statement.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {4}, pages = {349-357}, pmid = {38588073}, issn = {1536-5948}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Activities of Daily Living ; Workers' Compensation ; }, abstract = {Persistent symptoms are common after acute COVID-19, often referred to as long COVID. Long COVID may affect the ability to perform activities of daily living, including work. Long COVID occurs more frequently in those with severe acute COVID-19. This guidance statement reviews the pathophysiology of severe acute COVID-19 and long COVID and provides pragmatic approaches to long COVID symptoms, syndromes, and conditions in the occupational setting. Disability laws and workers' compensation are also addressed.}, } @article {pmid38587752, year = {2024}, author = {Appel, KS and Nürnberger, C and Bahmer, T and Förster, C and Polidori, MC and Kohls, M and Kraus, T and Hettich-Damm, N and Petersen, J and Blaschke, S and Bröhl, I and Butzmann, J and Dashti, H and Deckert, J and Dreher, M and Fiedler, K and Finke, C and Geisler, R and Hanses, F and Hopff, SM and Jensen, BO and Konik, M and Lehnert, K and de Miranda, SMN and Mitrov, L and Miljukov, O and Reese, JP and Rohde, G and Scherer, M and Tausche, K and Tebbe, JJ and Vehreschild, JJ and Voit, F and Wagner, P and Weigl, M and Lemhöfer, C and , }, title = {Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).}, journal = {Infection}, volume = {52}, number = {5}, pages = {1813-1829}, pmid = {38587752}, issn = {1439-0973}, support = {Grant No. 01KX2121//German Federal Ministry of Education and Research (BMBF) Network of University Medicine 2.0: "NUM 2.0"/ ; }, mesh = {Humans ; Male ; *COVID-19/epidemiology/diagnosis ; Female ; Middle Aged ; Germany/epidemiology ; Prospective Studies ; *Quality of Life ; *SARS-CoV-2 ; Aged ; Severity of Illness Index ; Adult ; Post-Acute COVID-19 Syndrome ; Patient Reported Outcome Measures ; Cohort Studies ; Surveys and Questionnaires ; Symptom Assessment ; }, abstract = {PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score.

METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L).

RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001).

CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities.

TRAIL REGISTRATION NUMBER: The cohort is registered at www.

CLINICALTRIALS: gov under NCT04768998.}, } @article {pmid38587211, year = {2024}, author = {Sviercz, F and Jarmoluk, P and Godoy Coto, J and Cevallos, C and Freiberger, RN and López, CAM and Ennis, IL and Delpino, MV and Quarleri, J}, title = {The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts.}, journal = {Journal of medical virology}, volume = {96}, number = {4}, pages = {e29597}, doi = {10.1002/jmv.29597}, pmid = {38587211}, issn = {1096-9071}, support = {//PICTO 2021-COVID secuelas-00005 to JQ, and ILE/ ; //Agencia Nacional de Promoción Científica y Tecnológica/ ; }, mesh = {Humans ; *Osteoclasts/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; SARS-CoV-2 ; Cell Differentiation ; }, abstract = {The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting toward an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.}, } @article {pmid38587102, year = {2024}, author = {Taylor, SA and Smyth, NJ}, title = {COVID-19 and the Postviral Syndrome of Long COVID: Where We Have Come from and Where We Are Going.}, journal = {Health & social work}, volume = {49}, number = {2}, pages = {71-75}, doi = {10.1093/hsw/hlae009}, pmid = {38587102}, issn = {1545-6854}, mesh = {Humans ; *COVID-19/epidemiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Postpoliomyelitis Syndrome ; }, } @article {pmid38586859, year = {2024}, author = {Tanking, C and Lakkananurak, C and Srisakvarakul, C and Jitpreeda, A and Threechod, K and Sukitpunyaroj, D}, title = {Postural orthostatic tachycardia syndrome and other autonomic dysfunctions following COVID-19: Incidence, characteristics, and associated factors.}, journal = {Journal of arrhythmia}, volume = {40}, number = {2}, pages = {230-236}, pmid = {38586859}, issn = {1880-4276}, abstract = {BACKGROUND: Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID-19. However, there is a lack of information regarding the incidence and associated factors in Asian population.

METHODS: A retro-prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR-proven COVID-19. Exclusion criteria were age under 18 years old, pregnancy, and pre-COVID-19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24-h Holter, 24-h ambulatory blood pressure, echocardiogram, and head-up tilt table (HUTT).

RESULTS: Seven hundred ninety-three patients were interviewed at 146 ± 37 days after COVID-19. The majority of patients were middle-aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C-reactive protein (CRP) was significantly higher (OR 1.01; p-value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms.

CONCLUSIONS: This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post-COVID-19 patients). The most common symptoms for these patients were fatigue and dyspnea.}, } @article {pmid38586062, year = {2024}, author = {Chaudhry, D and Khandelwal, S and Bahadur, C and Daniels, B and Bhattacharyya, M and Gangakhedkar, R and Desai, S and Das, J and , }, title = {Prevalence of long COVID symptoms in Haryana, India: a cross-sectional follow-up study.}, journal = {The Lancet regional health. Southeast Asia}, volume = {25}, number = {}, pages = {100395}, pmid = {38586062}, issn = {2772-3682}, abstract = {BACKGROUND: Emerging research indicates growing concern over long COVID globally, although there have been limited studies that estimate population burden. We aimed to estimate the burden of long COVID in three districts of Haryana, India, using an opportunity to link a seroprevalence study to follow-up survey of symptoms associated with long COVID.

METHODS: We used a population-based seroprevalence survey for COVID-19 conducted in September 2021 across Haryana, India. Adults from three purposively selected districts (Rohtak, Gurugram, and Jhajjar) were eligible to participate; 2205 of 3213 consented to participate in a survey on health status. Trained investigators administered a structured questionnaire that included demographic characteristics, self-reported symptoms of illness in the last six months before the survey, mental health, and history of COVID-19.

FINDINGS: Unadjusted regression estimates indicated positive correlations between symptomatic complaints and COVID-19 exposure, suggesting lingering effects of COVID-19 in this population. The overall physical morbidity index was higher among those who tested positive for COVID-19, as was the incidence of new cases. However, both morbidity and incidence became statistically insignificant after adjustment for multiple comparisons. Cough emerged as the only statistically significant individual persistent symptom. Sex-stratified analyses indicated significant estimates only for physical morbidity in women.

INTERPRETATION: This study is one of the first from India that uses a large population-based sample to examine longer term repercussions of COVID infections. The burden of long COVID should primarily be addressed in clinical settings, where specialised treatment for individual cases continues to evolve. Our analyses also provide insight into the size and nature of studies required to assess the population-level burden of long COVID.

FUNDING: This paper was produced under the auspices of the Lancet COVID 19 Commission India Task Force, which was supported financially by the Reliance Foundation. The Lancet COVID 19 Commission was set up in July 2020 and submitted its final report by October 2022. This report by the India Task Force was prepared during the same period.}, } @article {pmid38585924, year = {2024}, author = {Chen, Y and Zhang, D and Zhang, B and Wu, Q and Zhou, T and Tong, J and Lu, Y and Chen, J and Wang, H and Chisolm, D and Jhaveri, R and Kenney, R and Rothman, R and Rao, S and Williams, D and Hornig, M and Morris, J and Forrest, C}, title = {Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38585924}, issn = {2693-5015}, support = {R56 AG069880/AG/NIA NIH HHS/United States ; U01 TR003709/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; RF1 AG077820/AG/NIA NIH HHS/United States ; R01 LM013519/LM/NLM NIH HHS/United States ; R01 LM012607/LM/NLM NIH HHS/United States ; R01 AI130460/AI/NIAID NIH HHS/United States ; R56 AG074604/AG/NIA NIH HHS/United States ; R01 AG073435/AG/NIA NIH HHS/United States ; }, abstract = {Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.}, } @article {pmid38585665, year = {2024}, author = {Padilla, S and Ledesma, C and García-Abellán, J and García, JA and Fernández-González, M and de la Rica, A and Galiana, A and Gutiérrez, F and Masiá, M}, title = {Long COVID across SARS-CoV-2 variants, lineages, and sublineages.}, journal = {iScience}, volume = {27}, number = {4}, pages = {109536}, pmid = {38585665}, issn = {2589-0042}, abstract = {This prospective study aimed to determine the prevalence of long COVID in patients hospitalized for SARS-CoV-2 infection from March 2020 to July 2022 and assess the impact of different viral lineages. A total of 2,524 patients were followed up for 12 months, with persistent symptoms reported in 35.2% at one month, decreasing thereafter. Omicron variant patients initially showed higher symptom intensity, but this trend diminished over time. Certain viral lineages, notably Delta lineages AY.126 and AY.43, and Omicron sublineages BA.1.17, BA.2.56, and BA.5.1, consistently correlated with more severe symptoms. Overall, long COVID prevalence and severity were similar across SARS-CoV-2 variants. Specific lineages may influence post-COVID sequelae persistence and severity.}, } @article {pmid38583751, year = {2024}, author = {Benito-León, J and Lapeña, J and García-Vasco, L and Cuevas, C and Viloria-Porto, J and Calvo-Córdoba, A and Arrieta-Ortubay, E and Ruiz-Ruigómez, M and Sánchez-Sánchez, C and García-Cena, C}, title = {Exploring Cognitive Dysfunction in Long COVID Patients: Eye Movement Abnormalities and Frontal-Subcortical Circuits Implications via Eye-Tracking and Machine Learning.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.04.004}, pmid = {38583751}, issn = {1555-7162}, abstract = {BACKGROUND: Cognitive dysfunction is regarded as one of the most severe aftereffects following coronavirus disease 2019 (COVID-19). Eye movements, controlled by several brain areas, such as the dorsolateral prefrontal cortex and frontal-thalamic circuits, provide a potential metric for assessing cortical networks and cognitive status. We aimed to examine the utility of eye movement measurements in identifying cognitive impairments in long COVID patients.

METHODS: We recruited 40 long COVID patients experiencing subjective cognitive complaints and 40 healthy controls and used a certified eye-tracking medical device to record saccades and antisaccades. Machine learning was applied to enhance the analysis of eye movement data.

RESULTS: Patients did not differ from the healthy controls regarding age, sex, and years of education. However, the patients' Montreal Cognitive Assessment total score was significantly lower than healthy controls. Most eye movement parameters were significantly worse in patients. These included the latencies, gain (computed as the ratio between stimulus amplitude and gaze amplitude), velocities, and accuracy (evaluated by the presence of hypermetric or hypometria dysmetria) of both visually and memory-guided saccades; the number of correct memory saccades; the latencies and duration of reflexive saccades; and the number of errors in the antisaccade test. Machine learning permitted distinguishing between long COVID patients experiencing subjective cognitive complaints and healthy controls.

CONCLUSION: Our findings suggest impairments in frontal subcortical circuits among long COVID patients who report subjective cognitive complaints. Eye-tracking, combined with machine learning, offers a novel, efficient way to assess and monitor long COVID patients' cognitive dysfunctions, suggesting its utility in clinical settings for early detection and personalized treatment strategies. Further research is needed to determine the long-term implications of these findings and the reversibility of cognitive dysfunctions.}, } @article {pmid38580370, year = {2024}, author = {Simpson, SA and Evans, RA and Gilbert, HR and Branson, A and Barber, S and McIntosh, E and Ahmed, Z and Dean, SG and Doherty, PJ and Gardiner, N and Greaves, C and Daw, P and Ibbotson, T and Jani, B and Jolly, K and Mair, F and Ormandy, P and Smith, S and Singh, SJ and Taylor, R}, title = {Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial.}, journal = {BMJ open}, volume = {14}, number = {4}, pages = {e083255}, pmid = {38580370}, issn = {2044-6055}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Quality of Life ; Feasibility Studies ; Exercise Therapy ; Exercise ; *Self-Management ; Cost-Benefit Analysis ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.

METHODS AND ANALYSIS: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention.

ETHICS AND DISSEMINATION: The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public.

TRIAL REGISTRATION NUMBER: ISRCTN68786622.

PROTOCOL VERSION: 2.0 (16 May 2023).}, } @article {pmid38577738, year = {2024}, author = {Imeri, G and Conti, C and Caroli, A and Arrigoni, A and Bonaffini, P and Sironi, S and Novelli, L and Raimondi, F and Chiodini, G and Vargiu, S and Di Marco, F}, title = {Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component.}, journal = {Multidisciplinary respiratory medicine}, volume = {19}, number = {1}, pages = {}, pmid = {38577738}, issn = {1828-695X}, abstract = {BACKGROUND: There are uncertainties whether the impairment of lung diffusing capacity in COVID-19 is due to an alteration in the diffusive conductance of the alveolar membrane (Dm), or an alteration of the alveolar capillary volume (Vc), or a combination of both. The combined measurement DLNO and DLCO diffusion, owing to NO higher affinity and faster reaction rate with haemoglobin compared to CO, enables the simultaneous and rapid determination of both Vc and Dm. The aim of the present study was to better identify the precise cause of post-COVID-19 diffusion impairment.

METHODS: Using the combined NO and CO gas transfer techniques (DLNO and DLCO), it is possible to better understand whether gas exchange abnormalities are due to membrane or alveolar capillary volume components. The present study was aimed at evaluating pulmonary gas exchange one year after severe COVID-19.  Results: The cohort included 33 survivors to severe COVID-19 (median age 67 years, 70% male) with no pre-existing lung disease, who underwent clinical, lung function and imaging assessments at 12 months due to persistence of respiratory symptoms or radiological impairment. The gas exchange abnormalities were mainly determined by the compromise of the vascular component as demonstrated by vascular pattern of gas exchange impairment (i.e., DLNO/DLCO≥110%, 76% of the sample), and by a reduction of the Vc (73%), while the Dm was reduced only in 9% of the entire sample. We did not find a correlation between the gas exchange impairment and the extent of the chest CT alterations (DLCO p = 0.059 and DLNO p = 0.054), which on average were found to be mild (11% of the parenchyma).

CONCLUSION: In COVID-19 survivors who are still symptomatic or have minimal CT findings at one year, gas exchange abnormalities are determined by impairment of the vascular component, rather than the diffusive component of the alveolar membrane.}, } @article {pmid38577278, year = {2024}, author = {Marcilla-Toribio, I and Moratalla-Cebrián, ML and Notario-Pacheco, B and Escudero-Lopez, MA and Morales-Cuenca, N and Martinez-Andres, M}, title = {Gender differences in symptomatology, socio-demographic information and quality of life in Spanish population with long COVID condition: a cross-sectional study.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1355973}, pmid = {38577278}, issn = {2296-2565}, mesh = {*COVID-19/epidemiology ; Adult ; Cross-Sectional Studies ; Memory Disorders ; Female ; Humans ; European People ; Middle Aged ; Male ; Arthralgia ; Fatigue ; *Quality of Life ; Sex Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID patients experience a decrease in their quality of life due to the symptomatology produced by the disease. It is also important to understand how long COVID affects both men and women. The objective of this study is to examine the impact of long COVID symptomatology on the quality of life of Spanish adults from a gender perspective.

METHODS: An observational and cross-sectional study was carried out. Participants were able to complete an online questionnaire using an online platform. A sample of 206 people participated in the study.

RESULTS: The 80.6% of the sample were women with a mean age of 46.51 (±8.28) and the 19.4% were men with a mean age of 48.03 (±9.50). The medium score in the PAC19-QoL test was 141.47 (±24.96) and segmented by gender, 141.65 (±23.95) for women and 140.82 (±28.66) for men. The most common symptoms in women were muscle and joint pain (94.6%), fatigue (94.0%), discomfort (92.2%), difficulty concentrating (91.0%), and memory loss (88.6%). For men the symptoms included muscle and joint pain (97.5%) and fatigue (97.5%) both occupying first position, discomfort (92.0%), difficulty concentrating (90.0%), mood disturbances (90.0%), and memory loss (87.5%). The chi-square test showed statistical significance (p < 0.005) for socio-demographic information, quality of life scores, and long COVID symptoms by intensities.

CONCLUSION: This study shows that there are gender differences in the way that long COVID is experienced.}, } @article {pmid38577029, year = {2024}, author = {Wang, Y and Guo, L and Cui, D and Zhang, H and Zhang, Q and Ren, L and Wang, G and Zhang, X and Huang, T and Chen, L and Huang, L and Wang, X and Zhong, J and Wang, Y and Li, H and Wang, J and Cao, B}, title = {Immune Responses in Discharged COVID-19 Patients With and Without Long COVID Symptoms.}, journal = {Open forum infectious diseases}, volume = {11}, number = {4}, pages = {ofae137}, pmid = {38577029}, issn = {2328-8957}, abstract = {The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)-immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities.}, } @article {pmid38576710, year = {2024}, author = {Peng, Z and Zheng, Y and Yang, Z and Zhang, H and Li, Z and Xu, M and Cui, S and Lin, R}, title = {Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1341072}, pmid = {38576710}, issn = {2296-858X}, abstract = {BACKGROUND: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management.

OBJECTIVES: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety.

MATERIALS AND METHODS: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes.

RESULTS: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22).

CONCLUSION: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.}, } @article {pmid38575878, year = {2024}, author = {Kabir, MF and Yin, KN and Jeffree, MS and Ahmedy, FB and Zainudin, MF and Htwe, O and Jahan, S and Hossain, MZ and Hossain, KMA and Hossain, T and Jahid, IK and Chakrovorty, SK}, title = {Clinical presentation of post-COVID pain and its impact on quality of life in long COVID patients: a cross-sectional household survey of SARS-CoV-2 cases in Bangladesh.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {375}, pmid = {38575878}, issn = {1471-2334}, mesh = {Humans ; Bangladesh/epidemiology ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Headache/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: Pain is one of the prevalent Long COVID Symptoms (LCS). Pain interferes with the quality of life (QoL) and induces disease burden.

PURPOSE: The study aimed to elicit the clinical presentation of pain and determine the relationships between QoL and pain in LCS.

METHODS: This household cross-sectional study of 12,925 SARS-CoV-2 cases between July and December 2021 was carried out in eight administrative divisions of Bangladesh. Stratified random sampling from the cases retrieved from the Ministry of Health was employed. Symptom screening was performed through COVID-19 Yorkshire Rehabilitation Scale, and long COVID was diagnosed according to World Health Organization (WHO) criteria. The analyses were conducted using IBM SPSS (Version 20.00).

RESULTS: The prevalence of pain in long COVID was between 01 and 3.1% in the studied population. The study also found five categories of pain symptoms as LCS in Bangladesh: muscle pain 3.1% (95% CI; 2.4-3.8), chest pain 2.4% (95% CI; 1.8-3.1), joint pain 2.8% (95% CI; 2.2-2.3), headache 3.1% (95% CI; 2.4-3.8), and abdominal pain 0.3% (95% CI; 0.01-0.5). People with LCS as pain, multiple LCS, and longer duration of LCS had significantly lower quality of life across all domains of the WHOQOL-BREF (P < 0.001) compared to asymptomatic cases.

CONCLUSION: Three out of ten people with long COVID experience painful symptoms, which can significantly reduce their quality of life. Comprehensive rehabilitation can improve the symptoms and reduce the burden of the disease.}, } @article {pmid38575546, year = {2024}, author = {Tindle, R}, title = {Long COVID: Sufferers can take heart.}, journal = {Australian journal of general practice}, volume = {53}, number = {4}, pages = {238-240}, doi = {10.31128/AJGP-07-23-6896}, pmid = {38575546}, issn = {2208-7958}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38574425, year = {2024}, author = {Saheb Sharif-Askari, F and Ali Hussain Alsayed, H and Saheb Sharif-Askari, N and Saddik, B and Al Sayed Hussain, A and Halwani, R}, title = {Risk factors and early preventive measures for long COVID in non-hospitalized patients: analysis of a large cohort in the United Arab Emirates.}, journal = {Public health}, volume = {230}, number = {}, pages = {198-206}, doi = {10.1016/j.puhe.2024.02.031}, pmid = {38574425}, issn = {1476-5616}, mesh = {Adult ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; United Arab Emirates/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Risk Factors ; *Amides ; *Pyrazines ; }, abstract = {OBJECTIVES: Long COVID is characterized by persistent symptoms lasting for 4 weeks or more following the acute infection with SARS-CoV-2. Risk factors for long COVID and the impact of pre-COVID vaccination and treatment during acute COVID-19 remain uncertain. This study aimed to investigate patient-specific factors associated with long COVID in a large cohort of non-hospitalized adult patients with mild to moderate COVID-19 in Dubai.

STUDY DESIGN: Cohort study.

METHODS: The study included 28,375 non-hospitalized adult patients diagnosed with mild to moderate COVID-19 between January 1, 2021, and September 31, 2022, in Dubai, who were followed up for 90 days. The presence of long COVID symptoms was documented by physicians during patient visits to the family medicine department. Furthermore, long COVID-related risk factors were collected and analyzed, including patient demographics, comorbidities, pre-COVID vaccination status, and the COVID-related treatments received during the acute phase of the illness. Cox proportional hazard models were applied for the statistical analysis.

RESULTS: Among the cohort, 2.8% of patients experienced long COVID symptoms during the 90-day follow-up. Patients with long COVID tended to be younger, female, and of Caucasian race. Common symptoms included fatigue, muscle pain, respiratory symptoms, abdominal and neurological symptoms, allergic reactions, skin rashes, and hair loss. Risk factors for long COVID were identified as diabetes mellitus, asthma, and Vitamin D deficiency. Females and Caucasians had a higher risk of long COVID during the pre-Omicron period compared to the Omicron period. Pre-COVID vaccination was associated with a reduced risk of long COVID in all patient subgroups. Treatment with favipiravir or sotrovimab during the acute phase of COVID-19 was linked to a decreased risk of long COVID, although favipiravir showed limited effectiveness in the high-risk group.

CONCLUSION: This study contributes to the existing knowledge by identifying risk factors for long COVID among non-hospitalized patients and emphasizing the potential benefits of pre-COVID vaccination and timely treatment.}, } @article {pmid38574363, year = {2024}, author = {Stern, R and Bibi, M and Keltz, MD}, title = {Premature Ovarian Insufficiency After Coronavirus Disease 2019 (COVID-19): Autoimmune Follicle-Stimulating Hormone (FSH) and FSH Receptor Blockade.}, journal = {Obstetrics and gynecology}, volume = {143}, number = {6}, pages = {e149-e152}, pmid = {38574363}, issn = {1873-233X}, mesh = {Adult ; Female ; Humans ; Betacoronavirus ; Coronavirus Infections/immunology/complications/drug therapy ; *COVID-19/immunology/complications ; Follicle Stimulating Hormone/blood ; Pandemics ; Pneumonia, Viral/immunology/complications/drug therapy ; *Primary Ovarian Insufficiency/immunology/drug therapy ; *Receptors, FSH/antagonists & inhibitors ; *SARS-CoV-2/immunology ; }, abstract = {BACKGROUND: Since the onset of the coronavirus disease (COVID-19) pandemic, a variety of long-COVID-19 symptoms and autoimmune complications have been recognized.

CASES: We report three cases of autoimmune premature poor ovarian response in patients aged 30-37 years after mild to asymptomatic COVID-19 before vaccination, with nucleotide antibody confirmation. Two patients failed to respond to maximum-dose gonadotropins for more than 4 weeks, despite a recent history of response before having COVID-19. After a month of prednisone 30 mg, these two patients had normal follicle-stimulating hormone (FSH) levels, high oocyte yield, and blastocyst formation in successful in vitro fertilization cycles. All three patients have above-average anti-müllerian hormone levels that persisted throughout their clinical ovarian insufficiency. Two patients had elevated FSH levels, perhaps resulting from FSH receptor blockade. One patient, with a history of high response to gonadotropins 75 international units per day and below-normal FSH levels, had no ovarian response to more than a month of gonadotropins (525 international units daily), suggesting autoimmune block of the FSH glycoprotein and possible FSH receptor blockade.

CONCLUSION: Auto-antibody production in response to COVID-19 before vaccination may be a rare cause of autoimmune poor ovarian response. Although vaccination is likely protective, further study will be required to evaluate the effect of vaccination and duration of autoimmune FSH or FSH receptor blockade.}, } @article {pmid38574226, year = {2024}, author = {Ebell, MH}, title = {Cognitive Behavior Therapy Effective in Patients With Fatigue Associated With Long COVID.}, journal = {American family physician}, volume = {109}, number = {3}, pages = {Online}, pmid = {38574226}, issn = {1532-0650}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; Fatigue/etiology/therapy ; Treatment Outcome ; *Cognitive Behavioral Therapy ; *Fatigue Syndrome, Chronic/psychology/therapy ; }, } @article {pmid38572864, year = {2024}, author = {Yang, H and Guan, L and Yang, T and Ma, H and Liu, X and Li, X and Li, J and Tong, Z}, title = {Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.}, journal = {Journal of medical virology}, volume = {96}, number = {4}, pages = {e29566}, doi = {10.1002/jmv.29566}, pmid = {38572864}, issn = {1096-9071}, support = {2021YFC0863600//Ministry of Science and Technology of the People's Republic of China/ ; 2023YFC0872500//Ministry of Science and Technology of the People's Republic of China/ ; 2022-1-1061//Capital's Funds for Health Improvement and Research/ ; 82200007//National Natural Science Foundation of China/ ; Ggyfz202329//Reform and Development Program of Beijing Institute of Respiratory Medicine/ ; }, mesh = {Male ; Humans ; Female ; Middle Aged ; *COVID-19/therapy ; Prospective Studies ; Quality of Life ; Anxiety ; Arthralgia ; }, abstract = {As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.}, } @article {pmid38572142, year = {2024}, author = {Hu, K and Zhang, L}, title = {Challenges and Opportunities Associated with Lifting the Zero COVID-19 Policy in China.}, journal = {Exploratory research and hypothesis in medicine}, volume = {9}, number = {1}, pages = {71-75}, pmid = {38572142}, issn = {2472-0712}, support = {R37 CA277812/CA/NCI NIH HHS/United States ; }, abstract = {Chinese government lifted its "Zero COVID-19" policy in December 2022. The estimated COVDI-19 new cases and deaths after the policy change are 167-279 million (about 12.0% to 20.1% of the Chinese population) and 0.68-2.1 million, respectively. Recent data also revealed continuous drops in fertility rate and historically lowest growth in gross domestic production in China. Thus, balancing COVID-19 control and economic recovery in China is of paramount importance yet very difficult. Supply chain disruption, essential service reduction and shortage of intensive care units have been discussed as the challenges associated with lifting "Zero COVID-19" policy. The additional challenges may include triple epidemic of COVID-19, respiratory syncytial virus and influenza, mental health issues of healthcare providers, care givers and patients, impact on human mobility, lack of robust genomic and epidemiological data and long COVID-19. However, the policy-associated opportunities and other challenges are largely untouched, but warrant attention of and prompt reactions by the policy makers, healthcare providers, public health officials and other stakeholders. The associated benefits are quick reach of herd immunity, boost of economy and businesses activities and increase in social activities. At this moment, we must embrace the policy change, effectively mitigate its associated problems and timely and effectively maximize its associated benefits.}, } @article {pmid38571660, year = {2024}, author = {Marques, FRDM and Laranjeira, C and Carreira, L and Gallo, AM and Baccon, WC and Goes, HF and Salci, MA}, title = {Managing long COVID symptoms and accessing health services in Brazil: A grounded theory analysis.}, journal = {Heliyon}, volume = {10}, number = {7}, pages = {e28369}, pmid = {38571660}, issn = {2405-8440}, abstract = {BACKGROUND: The worldwide community has shown significant interest in researching the management of Long COVID. However, there is scarce evidence about the daily experiences of people living with Long COVID and their insights into the healthcare services provided to them.

AIMS: This study aims to understand the experience of Long COVID sufferers with their symptoms and in accessing health services.

METHOD: We employed Charmaz's grounded theory methodology, informed by constructivism, and applied the COREQ guidelines for qualitative research. Sixty-six Brazilians living with Long COVID participated in the study. The data was collected using semi-structured telephone interviews and analyzed using a constant comparative process.

FINDINGS: The findings refer firstly to the consequences of persistent Long COVID symptoms. Secondly, they describe how the disease trajectory required Long COVID sufferers to reorganize their routines and develop adaptive strategies. Lastly, they reflect a diverse array of both positive and negative interactions inside the healthcare system conveyed by individuals suffering from Long COVID. These elements converge towards the core category of the study: "The limbo of Long COVID sufferers: between the persistence of symptoms and access to health services".

CONCLUSIONS: Long COVID is characterized by its varied nature, including a range of physical and emotional repercussions experienced by individuals. There is a need for enhanced comprehension and discourse about Long COVID across several domains, including the general public, policy-making entities, and healthcare professionals. In this sense, the development of specialized services or the reinforcement of existing services to support long COVID sufferers is imperative.}, } @article {pmid38571295, year = {2024}, author = {Vojdani, A and Almulla, AF and Zhou, B and Al-Hakeim, HK and Maes, M}, title = {Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.}, journal = {Acta neuropsychiatrica}, volume = {36}, number = {3}, pages = {172-184}, doi = {10.1017/neu.2024.10}, pmid = {38571295}, issn = {1601-5215}, mesh = {Humans ; *Herpesvirus 6, Human/immunology ; *Fatigue Syndrome, Chronic/blood/immunology/virology ; Male ; Female ; *Immunoglobulin A/blood ; *Immunoglobulin M/blood ; *COVID-19/immunology/blood ; Adult ; *Activins/blood ; Middle Aged ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Antibodies, Viral/blood ; Herpesvirus 4, Human/immunology ; Biomarkers/blood ; Roseolovirus Infections/blood/immunology ; }, abstract = {BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID.

OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers.

METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR).

RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709).

CONCLUSION: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.}, } @article {pmid38570653, year = {2024}, author = {Graham, F}, title = {Daily briefing: Patients lead the way on long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-024-00985-x}, pmid = {38570653}, issn = {1476-4687}, } @article {pmid38570429, year = {2024}, author = {Schirinzi, T and Maftei, D and Maurizi, R and Albanese, M and Simonetta, C and Bovenzi, R and Bissacco, J and Mascioli, D and Boffa, L and Di Certo, MG and Gabanella, F and Francavilla, B and Di Girolamo, S and Mercuri, NB and Passali, FM and Lattanzi, R and Severini, C}, title = {Post-COVID-19 Hyposmia Does Not Exhibit Main Neurodegeneration Markers in the Olfactory Pathway.}, journal = {Molecular neurobiology}, volume = {61}, number = {11}, pages = {8921-8927}, pmid = {38570429}, issn = {1559-1182}, support = {SEED PNR (2021) "PROKINETICIN 2: a new potenzial neuroinflammatory biomarker in Alzheimer disease"//Sapienza Università di Roma/ ; DSB.AD006.371 "INVECCHIAMENTO ATTIVO E IN SALUTE (FOE 2022)//Ministero dell'Università e della Ricerca/ ; }, mesh = {Humans ; *COVID-19/complications ; Female ; Male ; *Anosmia/metabolism ; Middle Aged ; *Amyloid beta-Peptides/metabolism ; *Biomarkers/metabolism ; *Olfactory Pathways/metabolism/pathology ; *tau Proteins/metabolism ; Aged ; alpha-Synuclein/metabolism ; Neurodegenerative Diseases/metabolism/complications ; Olfactory Mucosa/metabolism/pathology/virology ; Neurofilament Proteins/metabolism ; Olfactory Receptor Neurons/metabolism ; Adult ; SARS-CoV-2 ; Olfaction Disorders/etiology/virology ; }, abstract = {The biological substrate of persistent post-COVID-19 hyposmia is still unclear. However, as many neurodegenerative diseases present with smell impairment at onset, it may theoretically reflect degeneration within the central olfactory circuits. However, no data still exist regarding the post-COVID-19 patients. As the olfactory neurons (ONs) mirror pathological changes in the brain, allowing for tracking the underlying molecular events, here, we performed a broad analysis of ONs from patients with persistent post-COVID-19 OD to identify traces of potential neurodegeneration. ONs were collected through the non-invasive brushing of the olfactory mucosa from ten patients with persistent post-COVID-19 hyposmia (lasting > 6 months after infection) and ten age/sex-matched controls. Immunofluorescence staining for protein quantification and RT-PCR for gene expression levels were combined to measure ONs markers of α-synuclein, amyloid-β, and tau pathology, axonal injury, and mitochondrial network. Patients and controls had similar ONs levels of oligomeric α-synuclein, amyloid-β peptide, tau protein, neurofilament light chain (NfL), cytochrome C oxidase subunit 3 (COX3), and the heat shock protein 60 (HSP60). Our findings thus did not provide evidence for synucleinopathy and amyloid-β mismetabolism or gross traces of neuronal injury and mitochondrial dysfunction within the olfactory system in the early phase of persistent post-COVID-19 hyposmia.}, } @article {pmid38568321, year = {2024}, author = {Jiang, Y and Sadun, RE}, title = {What the SARS-CoV-2 Pandemic Has Taught Us About Immunosuppression, Vaccinations, and Immune Dysregulation: The Rheumatology Experience.}, journal = {Current allergy and asthma reports}, volume = {24}, number = {4}, pages = {221-232}, pmid = {38568321}, issn = {1534-6315}, support = {T32 HD094671/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Humans ; United States ; SARS-CoV-2 ; *COVID-19/epidemiology/prevention & control/*complications ; *Rheumatology ; Pandemics/prevention & control ; COVID-19 Vaccines/therapeutic use ; Post-Acute COVID-19 Syndrome ; Immunosuppression Therapy ; Vaccination ; *Systemic Inflammatory Response Syndrome ; }, abstract = {PURPOSE OF REVIEW: This review reflects on the impact of the COVID-19 pandemic on the field of rheumatology, emphasizing resulting insights related to the risks of viral infections in immunosuppressed patients, vaccine immunogenicity in immunocompromised patients, and immune dysregulation in the setting of viral infection.

RECENT FINDINGS: During the pandemic, global patient registries provided real-time insights into the risk factors associated with severe COVID-19 outcomes in rheumatology patients. Updated evidence-based recommendations from the American College of Rheumatology (ACR) guided rheumatology practice during a time of considerable uncertainty. Studies on COVID-19 vaccines in immunocompromised populations enhanced our understanding of specific immunosuppressive therapies on vaccine efficacy. The immune dysregulation seen in severe COVID-19 underscored a role for immunomodulation in this and other severe infections. Furthermore, novel post-infectious conditions, namely multisystem inflammatory syndrome in children (MIS-C) and Long COVID, reshaped our understanding of post-viral syndromes and revealed novel pathological mechanisms. Lessons from the COVID-19 pandemic demonstrate the power of collaborative research. The scientific revelations from this dreadful time will, nonetheless, benefit the practice of rheumatology for years to come.}, } @article {pmid38567621, year = {2024}, author = {Dhuli, K and Medori, MC and Micheletti, C and Donato, K and Fioretti, F and Calzoni, A and Praderio, A and De Angelis, MG and Arabia, G and Cristoni, S and Nodari, S and Bertelli, M}, title = {Retraction Note: Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome.}, journal = {European review for medical and pharmacological sciences}, volume = {28}, number = {6}, pages = {2625}, doi = {10.26355/eurrev_202403_35774}, pmid = {38567621}, issn = {2284-0729}, abstract = {The article "Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome", by K. Dhuli, M.C. Medori, C. Micheletti, K. Donato, F. Fioretti, A. Calzoni, A. Praderio, M.G. De Angelis, G. Arabia, S. Cristoni, S. Nodari, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 13-19-DOI: 10.26355/eurrev_202312_34685-PMID: 38112944 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: - Unclear methodology and patient recruitment - Discrepancies among data reported in the text and tables - Unreliable results - Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors disagree with this retraction. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34685.}, } @article {pmid38566450, year = {2024}, author = {Martínez, S and Albóniga, OE and López-Huertas, MR and Gradillas, A and Barbas, C}, title = {Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.}, journal = {Journal of proteome research}, volume = {23}, number = {8}, pages = {3025-3040}, doi = {10.1021/acs.jproteome.3c00706}, pmid = {38566450}, issn = {1535-3907}, mesh = {Humans ; *COVID-19/blood/virology/metabolism ; *Metabolomics/methods ; *Mitochondria/metabolism ; *Lipidomics/methods ; *SARS-CoV-2 ; Male ; Female ; Middle Aged ; Aged ; Mass Spectrometry/methods ; Post-Acute COVID-19 Syndrome ; Metabolome ; Adult ; Citric Acid Cycle ; Ceramides/blood/metabolism ; }, abstract = {Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.}, } @article {pmid38565658, year = {2024}, author = {Fairbank, R}, title = {Long COVID still has no cure - so these patients are turning to research.}, journal = {Nature}, volume = {628}, number = {8006}, pages = {26-28}, doi = {10.1038/d41586-024-00901-3}, pmid = {38565658}, issn = {1476-4687}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/therapy/virology ; SARS-CoV-2/pathogenicity ; *Patients/psychology ; *Patient Advocacy ; *Clinical Trials as Topic/methods ; }, } @article {pmid38565574, year = {2024}, author = {Eligulashvili, A and Darrell, M and Gordon, M and Jerome, W and Fiori, KP and Congdon, S and Duong, TQ}, title = {Patients with unmet social needs are at higher risks of developing severe long COVID-19 symptoms and neuropsychiatric sequela.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7743}, pmid = {38565574}, issn = {2045-2322}, mesh = {Humans ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Chronic Disease ; Disease Progression ; *Asthma ; }, abstract = {This study investigated long COVID of patients in the Montefiore Health System COVID-19 (CORE) Clinics in the Bronx with an emphasis on identifying health related social needs (HRSNs). We analyzed a cohort of 643 CORE patients (6/26/2020-2/24/2023) and 52,089 non-CORE COVID-19 patients. Outcomes included symptoms, physical, emotional, and cognitive function test scores obtained at least three months post-infection. Socioeconomic variables included median incomes, insurance status, and HRSNs. The CORE cohort was older age (53.38 ± 14.50 vs. 45.91 ± 23.79 years old, p < 0.001), more female (72.47% vs. 56.86%, p < 0.001), had higher prevalence of hypertension (45.88% vs. 23.28%, p < 0.001), diabetes (22.86% vs. 13.83%, p < 0.001), COPD (7.15% vs. 2.28%, p < 0.001), asthma (25.51% vs. 12.66%, p < 0.001), lower incomes (53.81% vs. 43.67%, 1[st] quintile, p < 0.001), and more unmet social needs (29.81% vs. 18.49%, p < 0.001) compared to non-CORE COVID-19 survivors. CORE patients reported a wide range of severe long-COVID symptoms. CORE patients with unmet HRSNs experienced more severe symptoms, worse ESAS-r scores (tiredness, wellbeing, shortness of breath, and pain), PHQ-9 scores (12.5 (6, 17.75) vs. 7 (2, 12), p < 0.001), and GAD-7 scores (8.5 (3, 15) vs. 4 (0, 9), p < 0.001) compared to CORE patients without. Patients with unmet HRSNs experienced worse long-COVID outcomes compared to those without.}, } @article {pmid38564248, year = {2024}, author = {Le, LTH and Hoang, TNA and Nguyen, TT and Dao, TD and Do, BN and Pham, KM and Vu, VH and Pham, LV and Nguyen, LTH and Nguyen, HC and Tran, TV and Nguyen, TH and Nguyen, AT and Nguyen, HV and Nguyen, PB and Nguyen, HTT and Pham, TTM and Le, TT and Nguyen, TTP and Tran, CQ and Quach, HL and Nguyen, KT and Duong, TV}, title = {Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis.}, journal = {JMIR public health and surveillance}, volume = {10}, number = {}, pages = {e50189}, pmid = {38564248}, issn = {2369-2960}, mesh = {Adult ; Female ; Male ; Humans ; Latent Class Analysis ; *Sex Characteristics ; Cross-Sectional Studies ; Pandemics ; *COVID-19/epidemiology ; Cluster Analysis ; Life Style ; }, abstract = {BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences.

OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences.

METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group.

RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group.

CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.}, } @article {pmid38562097, year = {2024}, author = {Serrano Del Pueblo, VM and Serrano-Heras, G and Romero Sánchez, CM and Landete, PP and Rojas-Bartolome, L and Feria, I and Morris, RGM and Strange, B and Mansilla, F and Zhang, L and Castro-Robles, B and Arias-Salazar, L and López-López, S and Payá, M and Segura, T and Muñoz-López, M}, title = {Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {10}, pages = {3611-3623}, doi = {10.1093/brain/awae101}, pmid = {38562097}, issn = {1460-2156}, support = {PI21/00010//Spanish Instituto de Salud Carlos III/ ; //Víctor Serrano del Pueblo/ ; //EU REACTUE/ ; }, mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging ; *Neuropsychological Tests ; *Brain/diagnostic imaging/pathology ; Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Cognition/physiology ; Cognitive Dysfunction/psychology/diagnostic imaging ; SARS-CoV-2 ; }, abstract = {Between 2.5% and 28% of people infected with SARS-CoV-2 suffer long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy control subjects chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with long COVID assessed by Addenbrooke's Cognitive Examination-III screening test [overall cognitive level (OCLz) = -0.39 ± 0.12] was significantly below the infection recovered-controls (OCLz = +0.32 ± 0.16, P < 0.01). We observed that 48% of patients with long COVID had episodic memory deficit, with 27% also with impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy and higher radial diffusivity were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.}, } @article {pmid38561784, year = {2024}, author = {Reperant, L and Russell, CA and Osterhaus, A}, title = {Scientific highlights of the 9th ESWI Influenza Conference.}, journal = {One health outlook}, volume = {6}, number = {1}, pages = {5}, pmid = {38561784}, issn = {2524-4655}, abstract = {The European Scientific Working Group on Influenza (ESWI) held the 9th ESWI Influenza Conference in Valencia from 17-20 September 2023. Here we provide a summary of twelve key presentations, covering major topics on influenza virus, respiratory syncytial virus (RSV) and SARS coronavirus 2 (SARS-CoV-2) including: infection processes beyond acute respiratory disease, long COVID, vaccines against influenza and RSV, the implications of the potential extinction of influenza B virus Yamagata lineage, and the threats posed by zoonotic highly pathogenic avian influenza viruses.}, } @article {pmid38561719, year = {2024}, author = {Fang, C and Baz, SA and Sheard, L and Carpentieri, JD}, title = {"They seemed to be like cogs working in different directions": a longitudinal qualitative study on Long COVID healthcare services in the United Kingdom from a person-centred lens.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {406}, pmid = {38561719}, issn = {1472-6963}, support = {MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; COV-LT-0009//National Institute for Health and Care Research/ ; MC_PC_20051//UK Research and Innovation/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/epidemiology ; United Kingdom/epidemiology ; Delivery of Health Care ; Qualitative Research ; }, abstract = {BACKGROUND: The COVID-19 pandemic has presented significant challenges to the already over-stretched healthcare system in the United Kingdom (UK). These challenges are particularly pronounced for people living with the novel condition of Long COVID (LC) as they often face persistent and fluctuating symptoms, encountering prolonged uncertainty when seeking medical support. Despite a growing understanding of the healthcare challenges associated with LC, existing qualitative studies have predominantly focused on individual experiences rather than examining the structural aspects of healthcare.

METHODS: A longitudinal qualitative study with 80 participants and 12 healthcare practitioners was conducted in the UK to explore the healthcare experiences of those with LC. In total, 178 interviews (with attrition) were collected across two rounds, from November 2021 to March 2022, and from June to October 2022.

RESULTS: Embracing a person-centred framework that recognises and nurtures interconnected individual, relational, and existential needs, we investigated healthcare experiences related to LC across primary, secondary, and specialist integrated care. Using this perspective, we identified three overarching themes. Theme 1 addresses the persistent hurdle of accessing primary care as the initial point of contact for LC healthcare; Theme 2 underscores the complexity of navigating secondary care; and Theme 3 encapsulates the distinctive challenges of developing LC integrated care. These themes are interlinked, as people with LC often had to navigate or struggle between the various systems, with practitioners seeking to collaborate across the breadth of their professional responsibilities.

CONCLUSION: From a person-centred approach, we were able to identify the needs of those affected by lasting LC symptoms and comprehend how health services intricately influence these needs. The focus on healthcare systems also captures the nuanced impact that continuing healthcare struggles can have on people's identity. As such, our findings provide evidence to inform a more effective and sustainable delivery of person-centred care for people with LC across various healthcare settings and over time.}, } @article {pmid38561236, year = {2024}, author = {Nlandu, Y and Tannor, EK and Bafemika, T and Makulo, JR}, title = {Kidney damage associated with COVID-19: from the acute to the chronic phase.}, journal = {Renal failure}, volume = {46}, number = {1}, pages = {2316885}, pmid = {38561236}, issn = {1525-6049}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Kidney/pathology ; *Acute Kidney Injury/etiology/pathology ; Inflammation/pathology ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection is well established as a systemic disease including kidney damage. The entry point into the renal cell remains the angiotensin-converting enzyme 2 (ACE-2) receptor and the spectrum of renal lesions is broad, with a clear predominance of structural and functional tubular lesions. The most common form of glomerular injury is collapsing glomerulopathy (CG), which is strongly associated with apolipoprotein L1(APOL-1) risk variants. These acute lesions, which are secondary to the direct or indirect effects of SARS-CoV-2, can progress to chronicity and are specific to long COVID-19 in the absence of any other cause. Residual inflammation associated with SARS-CoV-2 infection, in addition to acute kidney injury (AKI) as a transitional state with or without severe histological lesions, may be responsible for greater kidney function decline in mild-to-moderate COVID-19. This review discusses the evidence for renal histological markers of chronicity in COVID-19 patients and triggers of low-grade inflammation that may explain the decline in kidney function in the post-COVID-19 period.}, } @article {pmid38561114, year = {2024}, author = {Faghy, PMA and Ashton, DRE and McNelis, MR and Arena, R and Duncan, DR}, title = {Attenuating post-exertional malaise in Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID: Is blood lactate monitoring the answer?.}, journal = {Current problems in cardiology}, volume = {49}, number = {6}, pages = {102554}, doi = {10.1016/j.cpcardiol.2024.102554}, pmid = {38561114}, issn = {1535-6280}, mesh = {Humans ; *Fatigue Syndrome, Chronic/blood/diagnosis ; *COVID-19/complications ; *Lactic Acid/blood ; SARS-CoV-2 ; Biomarkers/blood ; }, } @article {pmid38560644, year = {2024}, author = {Chen, DY and Huang, PI and Tang, KT}, title = {Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis.}, journal = {Rheumatology advances in practice}, volume = {8}, number = {2}, pages = {rkae027}, pmid = {38560644}, issn = {2514-1775}, abstract = {OBJECTIVES: Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients.

METHODS: We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case-control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis.

RESULTS: A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs.

CONCLUSION: The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.}, } @article {pmid38560433, year = {2024}, author = {Ruiyin, W and Qi, J and Tingting, W and Yuqin, Y and Yan, J and Kun, P}, title = {Long COVID outcomes following omicron wave in non-hospital population.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1377866}, pmid = {38560433}, issn = {2296-2565}, mesh = {Humans ; Female ; Male ; Adult ; Adolescent ; Young Adult ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Prospective Studies ; Cough ; Dyspnea ; Fatigue ; }, abstract = {BACKGROUND: The persistence of symptoms or the development of new symptoms following a diagnosis of SARS-CoV-2 has given rise to a multifaceted clinical condition referred to as "long COVID" (LC). The understanding of LC among China's non-hospitalized population continues to be insufficient. This investigation was designed to evaluate the protracted consequences amongst this demographic, as well as to identify the associated risk factors.

METHODS: This research constitutes a prospective cohort study focusing on non-hospitalized individuals, aged between 18 and 59, who have been positively diagnosed with COVID-19. Each participant was subjected to a sequence of questionnaire-based surveys, designed to evaluate symptoms as well as the status of depression and anxiety. A logistic regression model, adjusted for multiple variables, was employed to scrutinize the correlation between demographic elements, lifestyle attributes, and health-related risk factors in relation to conditions and symptoms post COVID-19 infection.

RESULTS: A total of 706 individuals participated in the 3 months follow-up, with 620 continuing on to the 6 months follow-up. The median age was 35 (28, 43) years, and 597 (85%) are female. Upon follow-up, Compared with patients without LC, patients with LC have a higher proportion of females (420 (87%) vs. 177 (79%); p = 0.010), were older (35 (29, 44) years vs. 33 (27, 41) years; p = 0.010) and have more comorbidities. Out of all participants, 483 (68.4%) reported experiencing at least one symptom at the 3 months mark, while 49.7% reported symptoms persisting at the 6 months mark. At the 3 months follow-up, the most prevalent persistent symptoms were cough (46%), fatigue (38%), and shortness of breath (34%). By the 6 months follow-up, fatigue (25%), shortness of breath (22%), and sleep disorders (16%) were the most commonly reported symptoms. Anxiety and depression were consistently reported as prevalent symptoms throughout the follow-up period. Most patient symptoms fade over time, with the quickest decreases observed in cough (from 46 to 9%), expectoration (from 26 to 6.3%), smell disorder (from 16 to 3.9%), and taste disorder (from 18 to 3.5%). Male and those possessing advanced educational qualifications exhibit a decreased susceptibility to the sustained incidence of coughing. Conversely, older age and the presence of comorbidities were identified as risk factors for persistent fatigue and shortness of breath.

CONCLUSION: In the after of COVID-19, it has been observed that the majority of patient symptoms tend to decrease over time. The primary residual symptoms noticed after a 6 month follow-up were fatigue, dyspnea, and sleep disturbances. However, it's noteworthy that the risk factors associated with these symptoms exhibit subtle variations. Furthermore, psychological sequelae, namely depression and anxiety, are frequently reported among COVID-19 survivors.}, } @article {pmid38558899, year = {2024}, author = {Ceklarz, J}, title = {Symptom intensity of post-COVID and long COVID syndromes in patients entering rehabilitation treatment.}, journal = {Reumatologia}, volume = {62}, number = {1}, pages = {18-25}, pmid = {38558899}, issn = {0034-6233}, abstract = {INTRODUCTION: The problem of post-COVID symptoms is still being analysed. Many of them may be related to other conditions, but the new appearance and greater intensity of some of them, e.g. fatigue, musculoskeletal pain, and neuropathic pain, seem to be related to a previous viral infection. Efforts are being made to determine in more detail the most characteristic symptoms of post-COVID syndrome. The conditions of rehabilitation after COVID-19 provide an opportunity for such observations. In rehabilitation centres and sanatoriums, it is possible to compare patients with post-COVID syndrome and other patients referred for rehabilitation, who constitute a natural control group. Such a comparison is the aim of the present work.

MATERIAL AND METHODS: The study included 59 post-COVID-19 patients and 57 sanatorium patients without COVID (non-COVID group) as a control group. The 31-element questionnaire ("Post-COVID syndrome symptoms assessment card") was part of the routine management of post-COVID patients referred for rehabilitation after symptomatic SARS-CoV-2 infection in Polish conditions. In the control group, the questionnaire was introduced as a part of a physical examination and an interview regarding the symptoms reported by the patient before standard rehabilitation. The questions were scored in the scale from 0 to a maximum of 10 points. Each patient gave informed consent to the use of the questionnaire for research purposes.

RESULTS: Symptoms of the highest intensity in the COVID-19 group were: feeling unwell after physical effort (avg. 6.25 points), chronic fatigue (avg. 5.97 points), dyspnoea on exertion (avg. 5.83 points), concentration disturbances (avg. 4.93), muscle pain (avg. 4.92), joint pain (avg. 4.86), memory disorders (avg. 4.81 points), sleep disorders (avg. 4.05 points), numbness of the limbs (avg. 3.73 points), tingling in the limbs (avg. 3.68 points).Symptoms of highest intensity in patients in the non-COVID-19 group: joint pain (avg. 4.61 points), tingling in the limbs (avg. 2.84 points), numbness of the limbs (avg. 2.79 points), muscle pain (avg. 2.11 points).There was no statistically significant difference between the group under examination and the control group in the following symptoms: fever, diarrhoea, abdominal pain, resting dyspnoea, olfactory disorders, joint pain, tingling in the limbs and numbness of the limbs.

CONCLUSIONS: The results of this study show symptoms of the highest intensity with post-COVID syndromes. However, also symptoms that are a problem both in post-COVID and non-COVID patients, i.e. joint pain, tingling in and numbness of the limbs were identified. This confirms that the control non-COVID group consisted of patients referred for rehabilitation treatment mainly due to musculoskeletal problems and chronic pain.}, } @article {pmid38558691, year = {2024}, author = {Aceituno, H and Barrancas, A and Quiroz-Bravo, F and Rigaud, D and Pérez-Cuesta, D and Tobar-Bustamante, A and Osores-Espinoza, M and Figueroa-Torres, C and Rojas-Catejo, C and Cisneros-Zamora, J}, title = {The Impact of Long COVID on Cognitive Performance and Sleep Quality: An Analysis of the Rancagua Chilean Study (RACHIS).}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e55089}, pmid = {38558691}, issn = {2168-8184}, abstract = {Background Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to prolonged symptoms post-recovery, commonly known as long-term coronavirus disease 2019 (COVID-19) or "long COVID." Neuropsychiatric consequences of long COVID include cognitive dysfunction and sleep disturbances, which significantly impair daily living. This study aimed to explore the impact of long COVID on cognitive performance and sleep quality in patients receiving outpatient care. Material and methods This study involved a random sample of 138 of 363 patients, corresponding to 38% of the cohort, who tested positive for SARS-CoV-2 via polymerase chain reaction (PCR) between May 2020 and April 2021. These unvaccinated, non-hospitalized individuals, predominantly exhibiting mild disease symptoms, were prospectively assessed 11 months post-positive PCR test. After informed consent, demographic data, memory, and concentration impairment levels were collected through interviews. Participants reporting cognitive symptoms underwent the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Pittsburgh Sleep Quality Index. Statistical analyses were conducted, including Student's t-test, Chi-square, Fisher's test, Kruskal-Wallis test, and Pearson correlation coefficient, with a significance threshold set at p<0.05. Results Of the 138 participants, 76 (55.1%) were female and 62 (44.9%) were male. The mean age was 45.9 years (± 13.0), with an average educational attainment of 10.4 years (± 3.7). Roughly 50% of the patients reported significant memory and concentration issues (p<0.001). Thirty-three participants underwent detailed cognitive assessments, revealing a 2:1 female-to-male ratio and a significantly higher prevalence of depression in female participants. Cognitive deficits were diagnosed in five (15.2%) participants via the MMSE and in 26 (78.8%) via the MOCA test, with notable deficits in visuospatial/executive functions, language repeat, and deferred recall (p<0.001). A lower educational level was correlated with higher cognitive deficits (p=0.03). Conclusion The study findings reveal that cognitive impairments, as a consequence of COVID-19, can persist up to 11 months post-infection. The MOCA test proved more effective in diagnosing these deficits and requires adjustments based on educational background. Sleep parameters remained largely unaffected in this cohort, likely attributed to the mild nature of the initial symptoms and the outpatient management of the disease.}, } @article {pmid38557961, year = {2024}, author = {Namjoshi, SS and Mast, A and Patel, AS}, title = {Review of long COVID in pediatric gastroenterology, hepatology, & nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {78}, number = {6}, pages = {1210-1212}, doi = {10.1002/jpn3.12199}, pmid = {38557961}, issn = {1536-4801}, support = {//None/ ; }, mesh = {Humans ; *COVID-19/prevention & control ; *Gastroenterology/organization & administration/methods ; Child ; *Pediatrics/methods/organization & administration ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38557284, year = {2024}, author = {Torreiter, S and So, P}, title = {An adaptive approach to developing a Long COVID rehabilitation program.}, journal = {Healthcare management forum}, volume = {37}, number = {4}, pages = {276-282}, doi = {10.1177/08404704241239867}, pmid = {38557284}, issn = {0840-4704}, mesh = {Humans ; *COVID-19 ; Ontario ; *SARS-CoV-2 ; Program Development ; Post-Acute COVID-19 Syndrome ; Patient Care Team/organization & administration ; }, abstract = {As more people became infected with the SARS-CoV-2 virus, it was anticipated that 10-20% of these individuals would develop a post-viral illness that would affect their ability to work and participate in daily activities and reduce quality of life. To support these patients, Unity Health Toronto opened the Outpatient Post-COVID Condition Rehabilitation Program in June 2021, with the aim of teaching patients how to manage their ongoing symptoms, and to maximize their independence and function. The program incorporated a multidisciplinary, patient-centred approach that leveraged group education and a virtual platform to allow patients from across Ontario to learn from one another and share experiences. Over the two years of the program, the multidisciplinary team continuously adapted to the new research on Long COVID and evolving needs of patients. This article will outline the development and evolution of the program.}, } @article {pmid38555403, year = {2024}, author = {Naidu, AS and Wang, CK and Rao, P and Mancini, F and Clemens, RA and Wirakartakusumah, A and Chiu, HF and Yen, CH and Porretta, S and Mathai, I and Naidu, SAG}, title = {Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID.}, journal = {NPJ science of food}, volume = {8}, number = {1}, pages = {19}, pmid = {38555403}, issn = {2396-8370}, abstract = {SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.}, } @article {pmid38554486, year = {2024}, author = {Fernández-de-Las-Peñas, C}, title = {[Long COVID management in Primary Care].}, journal = {Semergen}, volume = {50}, number = {4}, pages = {102240}, doi = {10.1016/j.semerg.2024.102240}, pmid = {38554486}, issn = {1578-8865}, mesh = {Humans ; *Primary Health Care/organization & administration ; *COVID-19/therapy ; Time Factors ; }, } @article {pmid38553722, year = {2024}, author = {Berentschot, JC and de Ridder, WA and Bek, LM and Heijenbrok-Kal, MH and Braunstahl, GJ and Remerie, SC and Stuip, Y and Ribbers, GM and Aerts, JGJV and Ista, E and Hellemons, ME and van den Berg-Emons, RJG and , }, title = {Patients' evaluation of aftercare following hospitalization for COVID-19: satisfaction and unmet needs.}, journal = {Respiratory research}, volume = {25}, number = {1}, pages = {145}, pmid = {38553722}, issn = {1465-993X}, support = {10430022010026/ZONMW_/ZonMw/Netherlands ; }, mesh = {Female ; Humans ; Male ; *Aftercare ; *COVID-19/therapy ; Hospitalization ; Patient Satisfaction ; Prospective Studies ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: Patient experiences with COVID-19 aftercare remain largely unknown. We evaluated COVID-19 aftercare from a patient perspective one year after hospitalization, assessing satisfaction and its associated factors, and unmet needs.

METHODS: The Satisfaction with COVID-19 Aftercare Questionnaire (SCAQ) was developed as part of a multicenter prospective cohort study and administered one year after hospital discharge. The SCAQ assesses (1) patient satisfaction, comprising information provision, rehabilitation, follow-up by hospitals and general practitioners (GPs), the most important aftercare topics, and overall satisfaction, and (2) unmet needs.

RESULTS: 487/561 (87%) COVID-19 patients completed the SCAQ, all had been discharged from the hospital between March 2020 and May 2021. Among responders, the median age of patients was 60 (IQR 54-67) years, 338 (69%) were male, and the median length of stay in the hospital was 13 (6-27) days. Patients were least satisfied with information on who could be contacted with questions when health problems arise (59% satisfied or very satisfied). Many patients (75%) received rehabilitation, most frequently community-based (70%). Across the different community-based therapies, ≥ 60% of patients were satisfied with shared-decision making and ≥ 70% with the received therapy; a majority (≥ 79%) indicated a preference for receiving the same therapy again if needed. Regarding follow-up by hospitals, 86% of patients received this follow-up, most frequently visiting a pulmonologist (96%), being generally satisfied with the received aftercare. Aftercare from GPs was received by 39% of patients, with 88% being satisfied with the GP's availability and 79% with referral to appropriate aftercare providers. Patients (> 50%) considered information-related items most important in aftercare. Overall, patients rated their satisfaction with aftercare 8/10 (7-9) points. Those who received medical rehabilitation (versus no rehabilitation, adjusted beta 0.61 [95%CI 0.11 to 1.11], p = 0.02) or aftercare by a hospital medical specialist (1.1 [0.46 to 1.64], p < 0.001) or GP (0.39 [0.053 to 0.72], p = 0.023) reported significantly higher satisfaction than those without such aftercare. Unmet needs were reported by 35% of patients, with lack of information (20%) and lack of additional aftercare and/or involvement of their GP (19%) being the most frequently reported.

CONCLUSION: Despite the forced quick development of COVID-19 aftercare, patients were generally satisfied. Follow-up by healthcare professionals and information provision is important to meet patients' aftercare needs.}, } @article {pmid38553294, year = {2024}, author = {Tsai, TY and Wu, JF and Weng, MT and Chuang, CH and Huang, TY and Tai, WC and Tai, CM and Chung, CS and Chen, CC and Lin, CP and Tsai, YY and Wei, SC}, title = {Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123}, number = {8}, pages = {866-874}, doi = {10.1016/j.jfma.2024.03.016}, pmid = {38553294}, issn = {0929-6646}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Taiwan/epidemiology ; Male ; Female ; Adult ; Middle Aged ; *Inflammatory Bowel Diseases/complications ; *SARS-CoV-2 ; COVID-19 Vaccines ; Aged ; Diarrhea/etiology/epidemiology ; Abdominal Pain/etiology ; Risk Factors ; Gastrointestinal Diseases/epidemiology/etiology ; }, abstract = {BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice.

METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization.

RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02).

CONCLUSION: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.}, } @article {pmid38552902, year = {2024}, author = {Lui, DTW and Xiong, X and Cheung, CL and Lai, FTT and Li, X and Wan, EYF and Chui, CSL and Chan, EWY and Cheng, FWT and Li, L and Chung, MSH and Lee, CH and Woo, YC and Tan, KCB and Wong, CKH and Wong, ICK}, title = {Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {30}, number = {6}, pages = {528-536}, doi = {10.1016/j.eprac.2024.03.389}, pmid = {38552902}, issn = {1530-891X}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Hong Kong/epidemiology ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Adult ; *Hypothyroidism/epidemiology ; *Thyroid Diseases/epidemiology ; Hyperthyroidism/epidemiology ; Incidence ; SARS-CoV-2 ; Cohort Studies ; Thyroxine/therapeutic use ; Risk Factors ; Thyroiditis/epidemiology ; Propensity Score ; Post-Acute COVID-19 Syndrome ; Antithyroid Agents/therapeutic use ; }, abstract = {OBJECTIVE: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19.

METHODS: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase.

RESULTS: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses.

CONCLUSION: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.}, } @article {pmid38552385, year = {2024}, author = {Al-Zadjali, J and Al-Lawati, A and Al Riyami, N and Al Farsi, K and Al Jarradi, N and Boudaka, A and Al Barhoumi, A and Al Lawati, M and Al Khaifi, A and Musleh, A and Gebrayel, P and Vaulont, S and Peyssonnaux, C and Edeas, M and Saleh, J}, title = {Reduced HDL-cholesterol in long COVID-19: A key metabolic risk factor tied to disease severity.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {79}, number = {}, pages = {100344}, pmid = {38552385}, issn = {1980-5322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cholesterol, HDL ; Risk Factors ; Ferritins ; Patient Acuity ; Chronic Disease ; }, abstract = {This controlled study investigated metabolic changes in non-vaccinated individuals with Long-COVID-19, along with their connection to the severity of the disease. The study involved 88 patients who experienced varying levels of initial disease severity (mild, moderate, and severe), and a control group of 29 healthy individuals. Metabolic risk markers from fasting blood samples were analyzed, and data regarding disease severity indicators were collected. Findings indicated significant metabolic shifts in severe Long-COVID-19 cases, mainly a marked drop in HDL-C levels and a doubled increase in ferritin levels and insulin resistance compared to the mild cases and controls. HDL-C and ferritin were identified as the leading factors predicted by disease severity. In conclusion, the decline in HDL-C levels and rise in ferritin levels seen in Long-COVID-19 individuals, largely influenced by the severity of the initial infection, could potentially play a role in the persistence and progression of Long-COVID-19. Hence, these markers could be considered as possible therapeutic targets, and help shape preventive strategies to reduce the long-term impacts of the disease.}, } @article {pmid38549864, year = {2024}, author = {Bocquet-Garçon, A}, title = {Impact of the SARS-CoV-2 Spike Protein on the Innate Immune System: A Review.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e57008}, pmid = {38549864}, issn = {2168-8184}, abstract = {The Spike protein enables the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to multiple receptors, including the angiotensin-converting enzyme 2 (ACE2). Scientific studies also indicate that Spike is involved in severe forms of coronavirus disease 2019 (COVID-19), "long-haul COVID diseases" - also known as "long COVID syndromes" or "post-acute sequelae of SARS-CoV-2 infection" (PACS) - or, recently, in adverse reactions to lipid nanoparticle-messenger ribonucleic acid (mRNA) vaccines or other anti-COVID19 products. Numerous mutations, notably within the subunit 1 of Spike (S1), prevent neutralization by antibodies, but more generally, the virus has developed numerous strategies to avoid immune system surveillance, especially type-I interferons (IFN-I). Meanwhile, a "hyperinflammatory" state, named "cytokine storm," sets in. However, what role does the Spike protein play in the immune escape mechanisms? Can its inflammatory activities affect IFN-I? Does Spike block IFN-I or hijack them for the virus benefits? What are the other potential consequences? This article was written to provide an up-to-date and more general overview of the impact of the Spike protein on the innate immune system and its effectors at the molecular level.}, } @article {pmid38549752, year = {2024}, author = {de Castro, GS and Gama, LR and Ramos, AF and Gatti da Silva, G and Teixeira, AAS and Cunha-Neto, E and de Souza, HP and Marie, SK and Talib, LL and Coelho, V and Kalil, J and de Araujo, AL and Ritto, AP and Belon, AR and Santos, AS and Barrére, APN and Sawamura, MVY and Lamas, CA and Baldi, BG and Carvalho, CRR and Kulikowski, LD and Damiano, RF and Imamura, M and Rosa Neto, JC and Lira, FS and Otoch, JP and Miguel, EC and Battistella, L and Forlenza, OV and Busatto, G and Seelaender, M}, title = {Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1295026}, pmid = {38549752}, issn = {2296-861X}, abstract = {INTRODUCTION: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

METHODS: In this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.

RESULTS: SRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.}, } @article {pmid38549689, year = {2024}, author = {Miao, Y and Ren, R and Shen, Z and Li, Y and Zhang, W and Bai, J and Zhu, D and Zhang, J and Guo, D and Tarimo, CS and Liu, R and Zhao, Q and Hu, J and Zhou, X and Dong, W}, title = {Quantifying the Adverse Effects of Long COVID on Individuals' Health After Infection: A Propensity Score Matching Design Study.}, journal = {Risk management and healthcare policy}, volume = {17}, number = {}, pages = {701-713}, pmid = {38549689}, issn = {1179-1594}, abstract = {OBJECTIVE: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.

METHODS: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients' socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of "persistent health problems after 4 weeks of COVID-19 infection" issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles' mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.

RESULTS: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals' health. After PSM, the non-long COVID cases' health scores remained higher than that of long COVID cases.

CONCLUSION: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.}, } @article {pmid38549052, year = {2024}, author = {Schmachtenberg, T and Königs, G and Roder, S and Müller, F and Müllenmeister, C and Schröder, D and El-Sayed, I}, title = {How do people with long COVID utilize COVID-19 vaccination and rehabilitation services and what are their experiences with these services? results of a qualitative study with 48 participants from Germany.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {915}, pmid = {38549052}, issn = {1471-2458}, mesh = {*COVID-19/prevention & control ; *Vaccines ; Humans ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; European People ; Adult ; Vaccination ; }, abstract = {BACKGROUND: Studies estimate that at least 7.5% of adults are affected by long-term symptoms such as fatigue or cognitive impairment after the acute phase of COVID-19. COVID-19 vaccination may reduce the risk of long COVID. Rehabilitation can have a positive impact on recovery. This study aims to present the experiences of people with long COVID with COVID-19 vaccination and rehabilitation. Such research is important because perceptions of these measures can impact healthcare utilization and health status.

METHODS: 48 adults with long COVID participated in this qualitative study, 25 of them in one-on-one interviews and 23 in focus groups. Participants were recruited via calls for participation on the websites and social media channels of two university hospitals and with the help of respondents' networks. The conversations were audio-recorded, transcribed, and analyzed using qualitative content analysis. Subsequently, the results were compared, interpreted, and discussed by scientific literature.

RESULTS: 35 study participants reported that they had received a COVID-19 vaccination and 16 of them stated that they had utilized a rehabilitation service. These participants had varying experiences with COVID-19 vaccination and rehabilitation. Nine of them stated that they developed long COVID despite vaccination before COVID-19. Ten participants reported vaccine reactions, and two participants reported severe side effects. Two participants reported persistent deterioration of their long COVID symptoms after vaccination. This led to uncertainty about the safety, benefits, and handling of COVID-19 vaccination. However, most participants perceived the vaccine as effective regarding milder COVID-19 sequelae. Four participants felt their rehabilitation was helpful and four participants felt it was unhelpful. Two persons found the combination of inpatient rehabilitation and rehabilitation sport helpful.

CONCLUSIONS: Several implications can be derived from this study: (1) researchers should explore the effects of COVID-19 vaccination on long COVID symptoms; (2) vaccination campaigns should be more responsive to the perspectives of people with long COVID on vaccination; (3) care planners should build rehabilitation facilities specialized in long COVID; (4) rehabilitation providers should train their professionals regarding long COVID and develop rehabilitation programs tailored to different clinical pictures.

TRIAL REGISTRATION: German register for clinical trials DRKS00026007, 09 September 2021.}, } @article {pmid38548364, year = {2024}, author = {Harrison, M and Rhodes, T and Lancaster, K}, title = {Constitution of Long COVID illness, patienthood and recovery: a critical synthesis of qualitative studies.}, journal = {BMJ open}, volume = {14}, number = {3}, pages = {e083340}, pmid = {38548364}, issn = {2044-6055}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Qualitative Research ; }, abstract = {OBJECTIVES: To investigate the lived experiences of Long COVID.

DESIGN: Critical interpretive synthesis of qualitative research.

DATA SOURCES: PubMed and Web of Science databases were searched on 14 September 2023.

ELIGIBILITY CRITERIA: Original peer-reviewed qualitative studies describing the experiences of Long COVID were eligible for inclusion.

DATA EXTRACTION AND SYNTHESIS: We used established qualitative synthesis methods to search, screen and manually code the included studies. Critical interpretation methods were used to analyse the data and develop synthetic constructs.

RESULTS: 68 articles were identified in the first phase of sampling, with 16 studies and 879 participants included in the final synthesis. The analysis of these studies was organised into three thematic constructions of Long COVID: (1) the illness, (2) the patient and (3) recovery. Long COVID was diversely characterised across study approaches, designs and findings but was underpinned by shared diagnostic logics, which shaped the identification and measurement of symptoms. The boundaries between different constitutions of Long COVID in qualitative accounts of illness experience were often imprecise. Slippages between different definitions of Long COVID had implications for patient experiences in relation to diagnosis, help-seeking and care, and expectations of recovery.

CONCLUSIONS: Long COVID is a site of multiple and diverse qualitative interpretation. Accounts of lived experience emphasise the constitutions of illness, patienthood and recovery as situated and emergent. The ongoing context-based negotiation of Long COVID is a defining qualitative feature of the condition. Approaches to researching, diagnosing and developing health interventions must be as adaptive as the varieties of Long COVID lived experience.}, } @article {pmid38548274, year = {2024}, author = {Comellas, AP and Fain, SB}, title = {Lung MRI identifies potentially treatable subtypes of long COVID.}, journal = {The European respiratory journal}, volume = {63}, number = {3}, pages = {}, doi = {10.1183/13993003.00381-2024}, pmid = {38548274}, issn = {1399-3003}, support = {S10 OD026960/OD/NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Lung/diagnostic imaging ; Phenotype ; Cluster Analysis ; }, } @article {pmid38548213, year = {2024}, author = {Howick, JF and Saric, P and Elwazir, M and Newman, DB and Pellikka, PA and Howick, AS and O'Horo, JC and Cooper, LT and Deshmukh, AJ and Ganesh, R and Hurt, R and Gersh, B and Bois, JP}, title = {A Pragmatic Study of Cardiovascular Disease During Long-Term COVID-19.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.03.011}, pmid = {38548213}, issn = {1555-7162}, abstract = {BACKGROUND: Many patients diagnosed with COVID-19 have persistent cardiovascular symptoms, but whether this represents a true cardiac process is unclear. This study assessed whether symptoms associated with long COVID among patients referred for cardiovascular evaluation are associated with objective abnormalities on cardiac testing to explain their clinical presentation.

METHODS: A retrospective cohort study of 40,462 unique patients diagnosed with COVID-19 at our tertiary referral was conducted and identified 363 patients with persistent cardiovascular symptoms a minimum of 4 weeks after polymerase chain reaction confirmed COVID-19 infection. Patients had no cardiovascular symptoms prior to COVID-19 infection. Each patient was referred for cardiovascular evaluation at a tertiary referral center. The incidence and etiology of abnormalities on cardiovascular testing among patients with long COVID symptoms are reported here. The cohort was subsequently divided into 3 categories based on the dominant circulating severe acute respiratory syndrome coronavirus 2 variant at the time of initial infection for further analysis.

RESULTS: Among 40,462 unique patients diagnosed with COVID-19 at our tertiary referral center from April 2020 to March 2022, 363 (0.9%) patients with long COVID were evaluated by Cardiology for possible cardiac sequelae from COVID and formed the main study cohort. Of these, 229 (63%) were vaccinated and 47 (12.9%) had severe initial infection, receiving inpatient treatment for COVID prior to developing long COVID symptoms. Symptoms were associated with a cardiac cause in 85 (23.4%), of which 52 (14.3%) were attributed to COVID; 39 (10.7%) with new cardiac disease from COVID, and 13 (3.6%) to worsening of pre-existing cardiac disease after COVID infection. The median troponin change in 45 patients with troponin measurements within 4 weeks of acute infection was +4 ng/dL (9 to 13 ng/dL). Among the total cohort with long COVID, 83.7% were diagnosed during the pre-Delta phase, 13.2% during the Delta phase, and 3.1% during the Omicron phase of the pandemic. There were 6 cases of myocarditis, 11 rhythm disorders, 8 cases of pericarditis, 5 suspected cases of endothelial dysfunction, and 33 cases of autonomic dysfunction.

CONCLUSION: This pragmatic retrospective cohort study suggests that patients with long COVID referred for cardiovascular evaluation infrequently have new, objective cardiovascular disease to explain their clinical presentation. A multidisciplinary, patient-centered approach is warranted for symptom management along with conservative use of diagnostic testing.}, } @article {pmid38547037, year = {2024}, author = {Link-Gelles, R and Rowley, EAK and DeSilva, MB and Dascomb, K and Irving, SA and Klein, NP and Grannis, SJ and Ong, TC and Weber, ZA and Fleming-Dutra, KE and McEvoy, CE and Akinsete, O and Bride, D and Sheffield, T and Naleway, AL and Zerbo, O and Fireman, B and Hansen, J and Goddard, K and Dixon, BE and Rogerson, C and Fadel, WF and Duszynski, T and Rao, S and Barron, MA and Reese, SE and Ball, SW and Dunne, MM and Natarajan, K and Okwuazi, E and Shah, AB and Wiegand, R and Tenforde, MW and Payne, AB}, title = {Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {73}, number = {12}, pages = {271-276}, pmid = {38547037}, issn = {1545-861X}, mesh = {Adult ; United States/epidemiology ; Humans ; Adolescent ; *Influenza, Human/epidemiology ; COVID-19 Vaccines ; *Influenza Vaccines ; *COVID-19/epidemiology/prevention & control ; Vaccination ; Hospitalization ; }, abstract = {In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.}, } @article {pmid38543815, year = {2024}, author = {Samarelli, F and Graziano, G and Gambacorta, N and Graps, EA and Leonetti, F and Nicolotti, O and Altomare, CD}, title = {Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal.}, journal = {Viruses}, volume = {16}, number = {3}, pages = {}, pmid = {38543815}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Aspirin/therapeutic use ; Anticoagulants/therapeutic use ; Blood Coagulation ; }, abstract = {People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds.}, } @article {pmid38543736, year = {2024}, author = {Giovanetti, M and Pannella, G and Altomare, A and Rocchi, G and Guarino, M and Ciccozzi, M and Riva, E and Gherardi, G}, title = {Exploring the Interplay between COVID-19 and Gut Health: The Potential Role of Prebiotics and Probiotics in Immune Support.}, journal = {Viruses}, volume = {16}, number = {3}, pages = {}, pmid = {38543736}, issn = {1999-4915}, mesh = {Humans ; Prebiotics ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; *Probiotics/therapeutic use ; Inflammation ; }, abstract = {The COVID-19 pandemic has profoundly impacted global health, leading to extensive research focused on developing strategies to enhance outbreak response and mitigate the disease's severity. In the aftermath of the pandemic, attention has shifted towards understanding and addressing long-term health implications, particularly in individuals experiencing persistent symptoms, known as long COVID. Research into potential interventions to alleviate long COVID symptoms has intensified, with a focus on strategies to support immune function and mitigate inflammation. One area of interest is the gut microbiota, which plays a crucial role in regulating immune responses and maintaining overall health. Prebiotics and probiotics, known for their ability to modulate the gut microbiota, have emerged as potential therapeutic agents in bolstering immune function and reducing inflammation. This review delves into the intricate relationship between long COVID, the gut microbiota, and immune function, with a specific focus on the role of prebiotics and probiotics. We examine the immune response to long COVID, emphasizing the importance of inflammation and immune regulation in the persistence of symptoms. The potential of probiotics in modulating immune responses, including their mechanisms in combating viral infections such as COVID-19, is discussed in detail. Clinical evidence supporting the use of probiotics in managing long COVID symptoms is summarized, highlighting their role as adjunctive therapy in addressing various aspects of SARS-CoV-2 infection and its aftermath.}, } @article {pmid38543708, year = {2024}, author = {Fournelle, D and Mostefai, F and Brunet-Ratnasingham, E and Poujol, R and Grenier, JC and Gálvez, JH and Pagliuzza, A and Levade, I and Moreira, S and Benlarbi, M and Beaudoin-Bussières, G and Gendron-Lepage, G and Bourassa, C and Tauzin, A and Grandjean Lapierre, S and Chomont, N and Finzi, A and Kaufmann, DE and Craig, M and Hussin, JG}, title = {Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.}, journal = {Viruses}, volume = {16}, number = {3}, pages = {}, pmid = {38543708}, issn = {1999-4915}, support = {174924//CIHR/Canada ; }, mesh = {Humans ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Serotherapy ; Immunocompromised Host ; Antibodies, Monoclonal ; Mutation ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Viral ; Antibodies, Neutralizing ; }, abstract = {Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.}, } @article {pmid38542351, year = {2024}, author = {Patarca, R and Haseltine, WA}, title = {Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542351}, issn = {1422-0067}, mesh = {Humans ; *HIV-1/physiology ; SARS-CoV-2/genetics/metabolism ; Transcriptional Activation ; HIV Long Terminal Repeat ; *COVID-19/genetics ; Gene Products, tat/genetics ; Lentivirus/genetics ; Gene Expression ; tat Gene Products, Human Immunodeficiency Virus/genetics/metabolism ; RNA, Viral/metabolism ; }, abstract = {Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to transacting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the replication-transcription complex might, therefore, transactivate viral and cellular RNAs in the transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution. Here, we show, by using primary and secondary structural comparisons, that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3. The coronaviral nucleocapsid C-terminal domains harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain, as do lentiviral Tat proteins. Although SARS-CoV-1 nucleocapsid transactivated gene expression in a replicon-based study, further experimental evidence for coronaviral transactivation and its possible implications is warranted.}, } @article {pmid38542177, year = {2024}, author = {Ricardi, C and Barachini, S and Consoli, G and Marazziti, D and Polini, B and Chiellini, G}, title = {Beta-Caryophyllene, a Cannabinoid Receptor Type 2 Selective Agonist, in Emotional and Cognitive Disorders.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542177}, issn = {1422-0067}, mesh = {Humans ; Adolescent ; *Cannabinoid Receptor Agonists/pharmacology/therapeutic use ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction ; Receptors, Cannabinoid ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Receptor, Cannabinoid, CB2 ; *Polycyclic Sesquiterpenes ; }, abstract = {Mental disorders account for one of the most prevalent categories of the burden of disease worldwide, with depression expected to be the largest contributor by 2030, closely followed by anxiety. The COVID-19 pandemic possibly exacerbated these challenges, especially amongst adolescents, who experienced isolation, disrupted routines, and limited healthcare access. Notably, the pandemic has been associated with long-term neurological effects known as "long-COVID", characterized by both cognitive and psychopathological symptoms. In general, psychiatric disorders, including those related to long-COVID, are supposed to be due to widespread inflammation leading to neuroinflammation. Recently, the endocannabinoid system (ECS) emerged as a potential target for addressing depression and anxiety pathophysiology. Specifically, natural or synthetic cannabinoids, able to selectively interact with cannabinoid type-2 receptor (CB2R), recently revealed new therapeutic potential in neuropsychiatric disorders with limited or absent psychotropic activity. Among the most promising natural CB2R ligands, the bicyclic sesquiterpene β-caryophyllene (BCP) has emerged as an excellent anti-inflammatory and antioxidant therapeutic agent. This review underscores BCP's immunomodulatory and anti-inflammatory properties, highlighting its therapeutic potential for the management of depression and anxiety.}, } @article {pmid38541785, year = {2024}, author = {Bielecka-Dabrowa, A and Sakowicz, A and Gryglewska-Wawrzak, K and Kapusta, J and Banach, M and Jankowski, P and Chudzik, M}, title = {The Effect of Sex on the Risk of Long-COVID and Cardiovascular Complications in Healthy Patients without Comorbidities: Data from a Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {6}, pages = {}, pmid = {38541785}, issn = {2077-0383}, abstract = {Background: The prevalence of long-COVID (LC) presents a significant challenge to healthcare systems globally. There are still some discrepancies on the role of sex as an independent risk factor of LC complications. Thus, we aimed to determine the differences in clinical and cardiovascular complications between males and females without comorbidities after COVID-19. Methods: Clinical data on the course of the disease with the accompanying symptoms and post-COVID-19 symptoms were compiled from both male and female subjects with a minimum 12-week interval after COVID-19 recovery. Next, the patients were followed for 12 months. ECG, echocardiography, 24 h ECG monitoring, 24 h ambulatory blood pressure monitoring (ABPM), and selected biochemical tests were performed. LC was diagnosed based on the World Health Organization (WHO) definition. To reduce the impact of confounders, i.e., body mass index (BMI) and age, on the results of the study, the nearest neighbour (NN) propensity score matching (PSM) method with a 1:1 ratio was used. Results: The results were obtained following the removal of cases with comorbidities from the database consisting of 1237 males and 2192 females, and PSM of the new database included 886 cases (443 males and 443 females). At both the 3-month and 1-year post-recovery marks, females consistently reported a higher frequency of LC symptoms compared to males (p < 0.001 for both comparisons). Moreover, after 1 year of follow-up, females exhibited a higher prevalence of LC compared to males, with rates of 14% versus 8.3%, respectively (p = 0.013). The symptoms that significantly differed between females and males in the 12-month follow-up were hair loss (5.4 vs. 0.7%, p < 0.001), memory and concentration disturbances (8.4 vs. 4.3%, p = 0.013), and headaches (4.3 vs. 1.4%, p = 0.008). Females presented lower mean arterial pressure (MAP) [89 (83-95) mmHg versus (vs.) 94 (89-100); p < 0.001] and lower pulse pressure (PP) [46 (42-52) mmHg vs. 51 (48-57); p < 0.001] in 24 h ABPM and more elevated heart rates (HRs) in 24 h ECG monitoring as well as arrhythmia (p < 0.001 and p = 0.018, respectively). Males had a higher occurrence of ECG abnormalities such as QRS >= 120 ms, ST-T changes, T inversion, arrhythmia, and QRS fragmentation (27.3% vs. 19.2%; p = 0.004). No significant differences were observed between males and females concerning physical activity levels, stress, fatigue, alcohol consumption, and smoking habits. Conclusions: One year post-COVID-19 recovery, regardless of age and BMI, healthy females more often suffered from LC symptoms than males. They had lower MAP and PP in 24 h ABPM, more often had higher HRs and arrhythmia in 24 h ECG monitoring, and fewer ECG abnormalities than males.}, } @article {pmid38541324, year = {2024}, author = {Sweis, JJG and Alnaimat, F and Esparza, V and Prasad, S and Azam, A and Modi, Z and Al-Awqati, M and Jetanalin, P and Sweis, NJ and Ascoli, C and Novak, RM and Rubinstein, I and Papanikolaou, IC and Sweiss, N}, title = {From Acute Infection to Prolonged Health Consequences: Understanding Health Disparities and Economic Implications in Long COVID Worldwide.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {3}, pages = {}, pmid = {38541324}, issn = {1660-4601}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; SARS-CoV-2 ; Health Inequities ; }, abstract = {The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.}, } @article {pmid38541055, year = {2024}, author = {Vrettou, CS and Vassiliou, AG and Keskinidou, C and Mourelatos, P and Asimakos, A and Spetsioti, S and Diamantopoulos, A and Jahaj, E and Antonoglou, A and Katsaounou, P and Vassiliadi, DA and Kotanidou, A and Dimopoulou, I}, title = {A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms.}, journal = {Journal of personalized medicine}, volume = {14}, number = {3}, pages = {}, pmid = {38541055}, issn = {2075-4426}, abstract = {BACKGROUND: this prospective observational study aims to assess serum levels of glial fibrillary acidic protein (GFAP), s100b, and total Tau in long-COVID patients, exploring correlations with symptoms, cognitive decline, mental health, and quality of life.

METHODS: Long-COVID patients visiting our outpatient clinic (February 2021-December 2022) were screened alongside age- and sex-matched controls. GFAP, s100b, and total Tau in serum were measured with ELISA. Cognitive function, depression, anxiety, post-traumatic stress disorder, and quality of life were evaluated using MoCA, HADS (depression and anxiety), IES-R, and SF-36, respectively.

RESULTS: Sixty-five long-COVID patients and 20 controls were included. GFAP levels were significantly higher in long-COVID patients (p = 0.031), though not correlating with the presence of long-COVID symptoms. S100b and total Tau showed no significant differences between patients and controls. Nervous system-related symptoms were reported in 47% of patients. High rates of cognitive decline (65.9%), depression (32.2%), anxiety (47.5%), and post-traumatic stress disorder (44.1%) were observed. Over 80% of the study population scored below normative cutoffs for SF-36, indicating a significant impact on quality of life.

CONCLUSIONS: in this long-COVID cohort with substantial psychological and cognitive symptoms, GFAP levels were elevated compared to controls, though not correlating with the presence of long-COVID symptoms.}, } @article {pmid38540252, year = {2024}, author = {Lazar, M and Sandulescu, M and Barbu, EC and Chitu-Tisu, CE and Andreescu, DI and Anton, AN and Erculescu, TM and Petre, AM and Duca, GT and Simion, V and Padiu, IF and Pacurar, CG and Rosca, R and Simian, TM and Oprea, CA and Ion, DA}, title = {The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view.}, journal = {Biomedicines}, volume = {12}, number = {3}, pages = {}, pmid = {38540252}, issn = {2227-9059}, abstract = {SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of infection but also after hospitalization. This is the consequence of the various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis is an important complication after COVID-19, found in up to 71% of patients after discharge. Our research is based on scientific articles indexed in PubMed; in the selection process, we used the following keywords: "lung fibrosis", "fibrosis mediators", "fibrosis predictors", "COVID-19", "SARS-CoV-2 infection", and "long COVID-19". In this narrative review, we aimed to discuss the current understanding of the mechanisms of initiation and progression of post-COVID-19 lung fibrosis (PC-19-LF) and the risk factors for its occurrence. The pathogenesis of pulmonary fibrosis involves various mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, and FGFR-1. The key cellular effectors involved in COVID-19 lung fibrosis are macrophages, epithelial alveolar cells, neutrophils, and fibroblasts. The main fibrosis pathways in SARS-CoV-2 infection include hypoxemia-induced fibrosis, macrophage-induced fibrosis, and viral-fibroblast interaction-induced fibrosis.}, } @article {pmid38540194, year = {2024}, author = {Alijotas-Reig, J and Anunciacion-Llunell, A and Esteve-Valverde, E and Morales-Pérez, S and Rivero-Santana, S and Trapé, J and González-García, L and Ruiz, D and Marques-Soares, J and Miro-Mur, F}, title = {Pituitary-Adrenal Axis and Peripheral Immune Cell Profile in Long COVID.}, journal = {Biomedicines}, volume = {12}, number = {3}, pages = {}, pmid = {38540194}, issn = {2227-9059}, support = {Synlab-JAR/2023//Synlab Group (Barcelona)/ ; UAB-Gravida-JAR/2023//Catedra UAB-Gravida de Medicina i Immunologia Reproductiva (Barcelona)/ ; SEMCC-JAR/2023//Sociedad Española de Medicina y Cirugía Cosmética (SEMCC, Barcelona)/ ; Althaia-JAR/2021//Fundacio Althaia-Aigües de Manresa (Barcelona)/ ; }, abstract = {In Long COVID, dysfunction in the pituitary-adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary-adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group.}, } @article {pmid38540167, year = {2024}, author = {Romanowska-Kocejko, M and Jędrzejewska, A and Braczko, A and Stawarska, K and Król, O and Frańczak, M and Harasim, G and Smoleński, RT and Hellmann, M and Kutryb-Zając, B}, title = {Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.}, journal = {Biomedicines}, volume = {12}, number = {3}, pages = {}, pmid = {38540167}, issn = {2227-9059}, support = {2019/35/D/NZ3/0351//National Science Center/ ; }, abstract = {Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.}, } @article {pmid38539680, year = {2024}, author = {Cenacchi, V and Furlanis, G and Menichelli, A and Lunardelli, A and Pesavento, V and Manganotti, P}, title = {Co-ultraPEALut in Subjective Cognitive Impairment Following SARS-CoV-2 Infection: An Exploratory Retrospective Study.}, journal = {Brain sciences}, volume = {14}, number = {3}, pages = {}, pmid = {38539680}, issn = {2076-3425}, abstract = {Neurological involvement following coronavirus disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an anti-inflammatory molecule) and luteolin (an anti-oxidant) have shown promising results as neuroinflammation antagonists. The aim of this study was to describe cognitive impairment in patients with post-COVID-19 treated with co-ultraPEALut. The Montreal Cognitive Assessment (MoCA), the Prospective-Retrospective Memory Questionnaire (PRMQ), the Fatigue Severity Scale (FSS), and a subjective assessment were administered at baseline and after 10 months. Patients treated with co-ultraPEALut were retrospectively compared with controls. Twenty-six patients treated with co-ultraPEALut showed a significant improvement in PRMQ (T0: 51.94 ± 10.55, T1: 39.67 ± 13.02, p < 0.00001) and MoCA raw score (T0: 25.76 ± 2.3, T1: 27.2 ± 2, p 0.0260); the MoCA-adjusted score and the FSS questionnaires also showed an improvement, even though it was not statistically significant; and 80.77% of patients reported a subjective improvement. In the control subjects (n = 15), the improvement was not as pronounced (PRMQ T0: 45.77 ± 13.47, T1: 42.33 ± 16.86, p 0.2051; FSS T0: 4.95 ± 1.57, T1: 4.06 ± 1.47, p 0.1352). Patients treated with co-ultraPEALut and corticosteroids were not statistically different from those treated with co-ultraPEALut alone. Neuro-post-COVID-19 patients treated with co-ultraPEALut scored better than controls in MoCA and PRMQ questionnaires after 10 months: this may support the importance of neuroinflammation modulation for neuro-long-COVID-19.}, } @article {pmid38539370, year = {2024}, author = {Torres, C and Maeda, K and Johnson, M and Jason, LA}, title = {Understanding Experiences of Youth with Long COVID: A Qualitative Approach.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {38539370}, issn = {2227-9067}, abstract = {There is limited information on the specific impacts of Long COVID in youth. Long COVID presents as persisting or new symptoms following initial COVID-19 infection. The aim of this study was to better understand how children and their families describe their experiences seeking diagnosis and support following the onset of symptoms of Long COVID. Six children and five caregivers located in the United States participated in this study. Study procedures included an online video interview with caregiver-child dyads. Interview transcriptions were then analyzed using a conventional approach to content analysis, with two independent coders generating themes. Eight themes emerged from this analysis including the severity of illness and symptomatology, difficulty surrounding the diagnostic process and not being believed, the impact on family and social connections, poor school functioning, positive coping, subsequent positive medical experiences, mental health, and knowledge of the medical field and healthcare experience. Themes revealed difficulty for youth and families in navigating the medical system and functioning in areas of daily life as well as areas of positive experiences related to coping and medical involvement. These findings also highlighted areas of needed improvement for the medical community and for research on Long COVID in youth.}, } @article {pmid38539172, year = {2024}, author = {Xie, PP and Zhang, Y and Niu, WK and Tu, B and Yang, N and Fang, Y and Shi, YH and Wang, FS and Yuan, X}, title = {Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {156}, pmid = {38539172}, issn = {1471-2466}, support = {2020YFC0860900//National Key Research and Development Program of China/ ; 2020YFC0860900//National Key Research and Development Program of China/ ; 2020YFC0860900//National Key Research and Development Program of China/ ; 2020YFC0860900//National Key Research and Development Program of China/ ; 2020YFC0860900//National Key Research and Development Program of China/ ; 20QNPY115//the Top-Notch Project for Youth Training/ ; }, mesh = {Humans ; Chronic Cough ; Longitudinal Studies ; *COVID-19/complications ; SARS-CoV-2 ; *Asthma/complications/drug therapy ; Adrenal Cortex Hormones/therapeutic use ; Cough ; Dyspnea/drug therapy ; Administration, Inhalation ; }, abstract = {BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era.

METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits.

RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days.

CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.}, } @article {pmid38537538, year = {2024}, author = {Bhattacharya, M and Chatterjee, S and Saxena, S and Nandi, SS and Lee, SS and Chakraborty, C}, title = {Current landscape of long COVID clinical trials.}, journal = {International immunopharmacology}, volume = {132}, number = {}, pages = {111930}, doi = {10.1016/j.intimp.2024.111930}, pmid = {38537538}, issn = {1878-1705}, mesh = {Humans ; *Clinical Trials as Topic ; *COVID-19/therapy ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Long COVID was reported as a multi-systemic condition after the infection of SARS-CoV-2, and more than 65 million people are suffering from this disease. It has been noted that around 10% of severe SARS-CoV-2 infected individuals are suffering from the enduring effects of long COVID. The symptoms of long COVID have also been noted in several mild or asymptomatic SARS-CoV-2 infected individuals. While limited reports on clinical trials investigating new therapeutics for long COVID exist, there is an abundance of scattered information available regarding these trials. This review explores the extensive literature search, and complete clinical trial database search to map the current status of long COVID clinical trials worldwide. The study listed about 110 long COVID clinical trials. In addition to conducting extensive long COVID clinical trials, we have comprehensively presented an overview of the condition, its symptoms, notable manifestations, associated clinical trials, the unique challenges it poses, and our recommendations for addressing long COVID.}, } @article {pmid38535610, year = {2024}, author = {Babicki, M and Kołat, D and Kałuzińska-Kołat, Ż and Kapusta, J and Mastalerz-Migas, A and Jankowski, P and Chudzik, M}, title = {The Course of COVID-19 and Long COVID: Identifying Risk Factors among Patients Suffering from the Disease before and during the Omicron-Dominant Period.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38535610}, issn = {2076-0817}, support = {The Medical Center of Postgraduate Education.//The Medical Center of Postgraduate Education./ ; }, abstract = {SARS-CoV-2 has acquired many mutations that influence the severity of COVID-19's course or the risk of developing long COVID. In 2022, the dominant SARS-CoV-2 variant was Omicron. This study aimed to compare the course of COVID-19 in the periods before and during the dominance of the Omicron variant. Risk factors for developing long COVID were also assessed. This study was based on stationary visits of patients after COVID-19 and follow-up assessments after 3 months. Clinical symptoms, comorbidities, and vaccination status were evaluated in 1967 patients. Of the analyzed group, 1308 patients (66.5%) were affected by COVID-19 in the period before the Omicron dominance. The prevalence of long COVID was significantly lower among patients of the Omicron group (47.7% vs. 66.9%, p < 0.001). The risk of long COVID was higher for women (OR: 1.61; 95% CI: 1.31, 1.99]) and asthmatics (OR: 1.46; 95% CI: 1.03, 2.07]). Conclusively, infection during the Omicron-dominant period was linked to a lower risk of developing long COVID. Females are at higher risk of developing long COVID independent of the pandemic period. Individuals affected by COVID-19 in the Omicron-dominant period experience a shorter duration of symptoms and reduced frequency of symptoms, except for coughing, which occurs more often.}, } @article {pmid38535608, year = {2024}, author = {Agouridis, AP and Mastori-Kourmpani, C and Antoniou, P and Konstantinou, P and Rizos, EC and Tsioutis, C}, title = {Beau's Lines and COVID-19; A Systematic Review on Their Association.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38535608}, issn = {2076-0817}, abstract = {BACKGROUND: Beau's lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix after severe disease. The aim of this study is to systematically report all evidence on the association of Beau's lines with COVID-19 infection or vaccination against COVID-19.

METHODS: PubMed and Scopus databases were searched up to January 2024 for articles reporting Beau's lines associated with COVID-19 infection or vaccination for COVID-19.

PROSPERO ID: CRD42024496830.

RESULTS: PubMed search identified 299 records while Scopus search identified 18 records. After screening the bibliography, nine studies including 35 cases were included in our systematic review. The studies were reported from different areas around the world. Included studies documented Beau's lines following COVID-19 vaccination (two studies) or after COVID-19 infection (seven studies). High variability was recorded in onset and resolution times among included cases, averaging 3 months and 6 months after COVID-19 infection, respectively. In the two studies reporting Beau's lines after vaccination, onset was at 7 days and 6 weeks and resolution occurred after 8 and 17 weeks, respectively.

CONCLUSIONS: To the best of our knowledge, this is the first systematic review reporting the association of Beau's lines with COVID-19 infection and vaccination. Severe immune response can result in the formation of these nail disorders. Of importance, Beau's lines represent a potential indicator of prior severe COVID-19 infection or vaccination for COVID-19, as well as a sign of long COVID-19 syndrome.}, } @article {pmid38535041, year = {2024}, author = {Babar, M and Jamil, H and Mehta, N and Moutwakil, A and Duong, TQ}, title = {Short- and Long-Term Chest-CT Findings after Recovery from COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38535041}, issn = {2075-4418}, abstract = {While ground-glass opacity, consolidation, and fibrosis in the lungs are some of the hallmarks of acute SAR-CoV-2 infection, it remains unclear whether these pulmonary radiological findings would resolve after acute symptoms have subsided. We conducted a systematic review and meta-analysis to evaluate chest computed tomography (CT) abnormalities stratified by COVID-19 disease severity and multiple timepoints post-infection. PubMed/MEDLINE was searched for relevant articles until 23 May 2023. Studies with COVID-19-recovered patients and follow-up chest CT at least 12 months post-infection were included. CT findings were evaluated at short-term (1-6 months) and long-term (12-24 months) follow-ups and by disease severity (severe and non-severe). A generalized linear mixed-effects model with random effects was used to estimate event rates for CT findings. A total of 2517 studies were identified, of which 43 met the inclusion (N = 8858 patients). Fibrotic-like changes had the highest event rate at short-term (0.44 [0.3-0.59]) and long-term (0.38 [0.23-0.56]) follow-ups. A meta-regression showed that over time the event rates decreased for any abnormality (β = -0.137, p = 0.002), ground-glass opacities (β = -0.169, p < 0.001), increased for honeycombing (β = 0.075, p = 0.03), and did not change for fibrotic-like changes, bronchiectasis, reticulation, and interlobular septal thickening (p > 0.05 for all). The severe subgroup had significantly higher rates of any abnormalities (p < 0.001), bronchiectasis (p = 0.02), fibrotic-like changes (p = 0.03), and reticulation (p < 0.001) at long-term follow-ups when compared to the non-severe subgroup. In conclusion, significant CT abnormalities remained up to 2 years post-COVID-19, especially in patients with severe disease. Long-lasting pulmonary abnormalities post-SARS-CoV-2 infection signal a future public health concern, necessitating extended monitoring, rehabilitation, survivor support, vaccination, and ongoing research for targeted therapies.}, } @article {pmid38534740, year = {2024}, author = {Kemerley, A and Gupta, A and Thirunavukkarasu, M and Maloney, M and Burgwardt, S and Maulik, N}, title = {COVID-19 Associated Cardiovascular Disease-Risks, Prevention and Management: Heart at Risk Due to COVID-19.}, journal = {Current issues in molecular biology}, volume = {46}, number = {3}, pages = {1904-1920}, pmid = {38534740}, issn = {1467-3045}, abstract = {The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus and the resulting COVID-19 pandemic have had devastating and lasting impact on the global population. Although the main target of the disease is the respiratory tract, clinical outcomes, and research have also shown significant effects of infection on other organ systems. Of interest in this review is the effect of the virus on the cardiovascular system. Complications, including hyperinflammatory syndrome, myocarditis, and cardiac failure, have been documented in the context of COVID-19 infection. These complications ultimately contribute to worse patient outcomes, especially in patients with pre-existing conditions such as hypertension, diabetes, or cardiovascular disease (CVD). Importantly and interestingly, reports have demonstrated that COVID-19 also causes myocardial injury in adults without pre-existing conditions and contributes to systemic complications in pediatric populations, such as the development of multisystem inflammatory syndrome in children (MIS-C). Although there is still a debate over the exact mechanisms by which such complications arise, understanding the potential paths by which the virus can influence the cardiovascular system to create an inflammatory environment may clarify how SARS-CoV-2 interacts with human physiology. In addition to describing the mechanisms of disease propagation and patient presentation, this review discusses the diagnostic findings and treatment strategies and the evolution of management for patients presenting with cardiovascular complications, focusing on disease treatment and prevention.}, } @article {pmid38533004, year = {2024}, author = {Cornelissen, MEB and Leliveld, A and Baalbaki, N and Gach, D and van der Lee, I and Nossent, EJ and Bloemsma, LD and Maitland-van der Zee, AH}, title = {Pulmonary function 3-6 months after acute COVID-19: A systematic review and multicentre cohort study.}, journal = {Heliyon}, volume = {10}, number = {6}, pages = {e27964}, pmid = {38533004}, issn = {2405-8440}, abstract = {AIMS: To describe pulmonary function 3-6 months following acute COVID-19, to evaluate potential predictors of decreased pulmonary function and to review literature for the effect of COVID-19 on pulmonary function.

MATERIALS AND METHODS: A systematic review and cohort study were conducted. Within the P4O2 COVID-19 cohort, 95 patients aged 40-65 years were recruited from outpatient post-COVID-19 clinics in five Dutch hospitals between May 2021-September 2022. At 3-6 months post COVID-19, medical records data and biological samples were collected and questionnaires were administered. In addition, pulmonary function tests (PFTs), including spirometry and transfer factor, were performed. To identify factors associated with PFTs, linear regression analyses were conducted, adjusted for covariates.

RESULTS: In PFTs (n = 90), mean ± SD % of predicted was 89.7 ± 18.2 for forced vital capacity (FVC) and 79.8 ± 20.0 for transfer factor for carbon monoxide (DLCO). FVC was
CONCLUSION: A low DLCO 3-6 months following acute COVID-19 was observed more often than a low FVC, both in the P4O2 COVID-19 study and the literature review.}, } @article {pmid38532741, year = {2024}, author = {Braig, S and Peter, RS and Nieters, A and Kräusslich, HG and Brockmann, SO and Göpel, S and Kindle, G and Merle, U and Steinacker, JM and Kern, WV and Rothenbacher, D}, title = {Post-COVID syndrome and work ability 9-12 months after a SARS-CoV-2 infection among over 9000 employees from the general population.}, journal = {IJID regions}, volume = {10}, number = {}, pages = {67-74}, pmid = {38532741}, issn = {2772-7076}, abstract = {OBJECTIVES: Evidence on the work-related societal impact of long-term health-related consequences following SARS-CoV-2 is emerging. We characterize the modified work ability index (mWAI) of employees 6 to 12 months after an acute infection compared to pre-infection.

METHODS: Analyses were based on a population-based, multi-center cross-sectional study including employees aged 18-65 years with positive SARS-CoV-2 polymerase chain reaction (tested between October 2020-April 2021 in defined geographic regions in Germany). Prevalences and results of adjusted logistic regression analyses were given.

RESULTS: In 9752 employees (mean age 45.6 years, 58% females, response 24%), n = 1217 (13.1%) participants were regarded as having low mWAI compared to pre-infection. Outpatient medical treatment, inpatient treatment, and admission to intensive care during infection were associated with mWAI <15[th] percentile (P15, each odds ratio [OR] >3.0). Post-COVID symptom clusters most strongly linked to mWAI
CONCLUSION: Our findings revealed risk factors of mWAI
METHODS: The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC.

RESULTS: We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes.

CONCLUSION: The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.}, } @article {pmid38532277, year = {2024}, author = {Lytzen, AA and Helt, TW and Christensen, J and Lund, TK and Kalhauge, A and Rönsholt, FF and Podlekavera, D and Arndal, E and Lebech, AM and Hanel, B and Katzenstein, TL and Berg, RMG and Mortensen, J}, title = {Pulmonary diffusing capacity for carbon monoxide and nitric oxide after COVID-19: A prospective cohort study (the SECURe study).}, journal = {Experimental physiology}, volume = {109}, number = {5}, pages = {652-661}, pmid = {38532277}, issn = {1469-445X}, support = {101390//TrygFonden/ ; 20045//TrygFonden/ ; }, mesh = {Humans ; *COVID-19/physiopathology ; *Pulmonary Diffusing Capacity ; *Carbon Monoxide/metabolism ; Male ; Female ; *Nitric Oxide/metabolism ; Middle Aged ; Prospective Studies ; Aged ; SARS-CoV-2 ; Lung/physiopathology ; Adult ; }, abstract = {Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID-19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID-19. An initial cohort of 148 patients diagnosed with COVID-19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single-breath method at 5.7 months follow-up. All patients with at least one abnormal DL,CO,NO metric (n = 87) were revaluated at 12.5 months follow-up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5 months, physical performance was assessed using a 30 s sit-to-stand test and the 6 min walk test. Approximately 60% of patients exhibited a severity-dependent decline in at least one DL,CO,NO metric at 5.7 months follow-up. At 12.5 months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two-thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity-dependent decline in DL,NO and DL,CO observed at 5.7 months after COVID-19 appears to be reduced consistently at 12.5 months follow-up in the majority of patients, despite marked improvements in physical performance.}, } @article {pmid38532129, year = {2024}, author = {Li, X and Ding, G and Li, S and Liu, C and Zheng, X and Luo, J and He, S and Zeng, F and Huang, X and Zeng, F}, title = {Proteomic characteristics of the treatment trajectory of patients with COVID-19.}, journal = {Archives of virology}, volume = {169}, number = {4}, pages = {84}, pmid = {38532129}, issn = {1432-8798}, support = {ZDYF0001//Dazhou Science and Technology Bureau/ ; 22ZDYF0020//Dazhou Science and Technology Bureau/ ; 21ZDYF0021//Dazhou Science and Technology Bureau/ ; 21CDDZ-26//Dazhou Science and Technology Bureau/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Proteomics/methods ; Pandemics ; COVID-19 Drug Treatment ; Biomarkers ; }, abstract = {The ongoing COVID-19 pandemic caused by SARS-CoV-2 has prompted global concern due to its profound impact on public health and the economy. Effective treatment of COVID-19 patients in the acute phase or of those with long COVID is a major challenge. Using data-independent acquisition (DIA) technology, we performed proteomic profiling on plasma samples from 22 COVID-19 patients and six healthy controls at Dazhou Central Hospital. Random forest and least absolute shrinkage and selection operator algorithms were used for analysis at various COVID-19 treatment stages. We identified 79 proteins that were differentially expressed between COVID-19 patients and healthy controls, mainly involving pathways associated with cell processes and binding. Across different treatment stages of COVID-19, five proteins-PI16, GPLD1, IGFBP3, KRT19, and VCAM1-were identified as potential molecular markers for dynamic disease monitoring. Furthermore, the proteins BTD, APOM, IGKV2-28, VWF, C4BPA, and C7 were identified as candidate biomarkers for distinguishing between SARS-CoV-2 positivity and negativity. Analysis of protein change profiles between the follow-up and healthy control groups highlighted cardiovascular changes as a concern for patients recovering from COVID-19. Our study revealed the infection profiles of SARS-CoV-2 at the protein expression level comparing different phases of COVID-19. DIA mass spectrometry analysis of plasma samples from COVID-19 patients undergoing treatment identified key proteins involved in signaling pathways that might be used as markers of the recovery phase. These findings provide insight for the development of therapy options and suggest potential blood biomarkers for COVID-19.}, } @article {pmid38532037, year = {2024}, author = {Wu, X and Novakovic, VA and Shi, J}, title = {Connective tissue disorders in COVID-19: Reply to "People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing".}, journal = {Angiogenesis}, volume = {27}, number = {2}, pages = {125-127}, pmid = {38532037}, issn = {1573-7209}, mesh = {Humans ; *Wound Healing ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Connective Tissue ; }, abstract = {Connective tissue serves as a framework for other tissues and organs, supporting their functions, shielding them from harmful factors, and aiding repair. In COVID-19, damaged endothelial cells (ECs), increased endothelial permeability, and thrombi contribute to the connective tissue disorders. Even post-recovery, the damage to ECs and connective tissues persists, resulting in long COVID. Individuals with connective tissue disorders are prone to developing severe COVID-19 and experiencing long COVID symptoms. It is advised that these patients receive at least three vaccine doses, undergo early prophylactic antithrombotic therapy during acute COVID-19, and maintain prophylactic anticoagulant treatment in cases of long COVID.}, } @article {pmid38527781, year = {2024}, author = {Seo, JW and Kim, SE and Kim, Y and Kim, EJ and Kim, T and Kim, T and Lee, SH and Lee, E and Lee, J and Seo, YB and Jeong, YH and Jung, YH and Choi, YJ and Song, JY}, title = {Updated Clinical Practice Guidelines for the Diagnosis and Management of Long COVID.}, journal = {Infection & chemotherapy}, volume = {56}, number = {1}, pages = {122-157}, pmid = {38527781}, issn = {2093-2340}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {"Long COVID" is a term used to describe a condition when the symptoms and signs associated with coronavirus disease 2019 (COVID-19) persist for more than three months among patients infected with COVID-19; this condition has been reported globally and poses a serious public health issue. Long COVID can manifest in various forms, highlighting the need for appropriate evaluation and management by experts from various fields. However, due to the lack of clear clinical definitions, knowledge of pathophysiology, diagnostic methods, and treatment protocols, it is necessary to develop the best standard clinical guidelines based on the scientific evidence reported to date. We developed this clinical guideline for diagnosing and treating long COVID by analyzing the latest research data collected from the start of the COVID-19 pandemic until June 2023, along with the consensus of expert opinions. This guideline provides recommendations for diagnosis and treatment that can be applied in clinical practice, based on a total of 32 key questions related to patients with long COVID. The evaluation of patients with long COVID should be comprehensive, including medical history, physical examination, blood tests, imaging studies, and functional tests. To reduce the risk of developing long COVID, vaccination and antiviral treatment during the acute phase are recommended. This guideline will be revised when there is a reasonable need for updates based on the availability of new knowledge on the diagnosis and treatment of long COVID.}, } @article {pmid38527615, year = {2024}, author = {Coste, J and Delpierre, C and Richard, JB and Alleaume, C and Gallay, A and Tebeka, S and Lemogne, C and Robineau, O and Steichen, O and Makovski, TT}, title = {Prevalence of long COVID in the general adult population according to different definitions and sociodemographic and infection characteristics. A nationwide random sampling survey in France in autumn 2022.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {7}, pages = {924-929}, doi = {10.1016/j.cmi.2024.03.020}, pmid = {38527615}, issn = {1469-0691}, mesh = {Humans ; France/epidemiology ; *COVID-19/epidemiology ; Male ; Prevalence ; Middle Aged ; Female ; Adult ; Cross-Sectional Studies ; Aged ; *SARS-CoV-2 ; Young Adult ; Post-Acute COVID-19 Syndrome ; Adolescent ; Aged, 80 and over ; Surveys and Questionnaires ; Sociodemographic Factors ; }, abstract = {OBJECTIVES: Long COVID has been recognized since early 2020, but its definition is not unanimous, which complicates epidemiological assessments. This study estimated the prevalence of long COVID based on several definitions and severity thresholds in the adult population of mainland France and examined variations according to sociodemographic and infection characteristics.

METHODS: A cross-sectional survey using random sampling was conducted in August-November 2022. Participants declaring SARS-CoV-2 infection were assessed for infection dates and context, post-COVID symptoms (from a list of 31, with onset time, daily functioning impact, and alternative diagnosis), and perceived long COVID. Long COVID prevalence was estimated according to the WHO, National Institute for Health and Care Excellence, United States National Centre for Health Statistics, and United Kingdom Office for National Statistics definitions.

RESULTS: Of 10 615 participants, 5781 (54.5%) reported SARS-CoV-2 infection, with 123-759 (1.2-13.4%) having long COVID, depending on the definition. The prevalence of WHO post-COVID condition (PCC) was 4.0% (95% CI: 3.6-4.5) in the overall population and 8.0% (95% CI: 7.0-8.9) among infected individuals. Among the latter, the prevalence varied from 5.3% (men) to 14.9% (unemployed) and 18.6% (history of hospitalization for COVID-19). WHO-PCC overlapped poorly with other definitions (kappa ranging from 0.18 to 0.59) and perceived long COVID (reported in only 43% of WHO-PCC).

DISCUSSION: Regardless of its definition, long COVID remains a significant burden in the French adult population that deserves surveillance, notably for forms that strongly impact daily activities. More standardized definitions will improve integrated surveillance of, and better research on, long COVID.}, } @article {pmid38526160, year = {2024}, author = {d'Entremont-Harris, M and Ramsey, TD and Pelletier, É and Goodall, B and Barrett, L}, title = {Reply to Antinori and Bausch-Jurken.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {2}, pages = {524-526}, doi = {10.1093/infdis/jiae128}, pmid = {38526160}, issn = {1537-6613}, } @article {pmid38526146, year = {2024}, author = {González-Alvarez, F and Estañol, B and González-Hermosillo, JA and Gómez-Pérez, FJ and Tamez-Torres, KM and Peña, E and Cantú, C and Chiquete, E and Sifuentes-Osornio, J and Alba-Lorenzo, MDC and Celestino-Montelongo, DA and Salazar-Calderón, GE and Aceves Buendia, JJ}, title = {Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.}, journal = {Journal of hypertension}, volume = {42}, number = {5}, pages = {928-932}, pmid = {38526146}, issn = {1473-5598}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/complications/drug therapy/diagnosis ; *Orthostatic Intolerance/complications ; Histamine ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.}, } @article {pmid38525993, year = {2024}, author = {Naunheim, MR and DeVore, EK and Huston, MN and Song, PC and Franco, RA and Bhattacharyya, N}, title = {Increasing Prevalence of Voice Disorders in the USA: Updates in the COVID Era.}, journal = {The Laryngoscope}, volume = {134}, number = {8}, pages = {3713-3718}, doi = {10.1002/lary.31409}, pmid = {38525993}, issn = {1531-4995}, mesh = {Humans ; *COVID-19/epidemiology ; *Voice Disorders/epidemiology ; Male ; United States/epidemiology ; Female ; Prevalence ; Adult ; Middle Aged ; Aged ; Young Adult ; SARS-CoV-2 ; Adolescent ; Health Surveys ; }, abstract = {OBJECTIVE: To estimate the current prevalence of voice disorders among adults in the United States; to determine the association of individual factors with voice disorders.

METHODS: The 2022 National Health Interview Survey (NHIS) was analyzed to identify adults reporting voice problems in the past 12 months. Demographics were assessed, as well as the duration, severity, and resolution of the voice problem. The relationship between voice problems, gender, lost workdays, and long COVID was investigated. A comparison to the 2012 NHIS was made to determine changes in voice disorder prevalence.

RESULTS: 29.9 million Americans (95%CI[28.3-31.5]) annually report a voice problem, representing 12.2% of the population (95%CI[11.7-12.8%]). Overall, 26.8% and 13.2% reported the severity of their voice problem as moderate or severe, respectively. Only 5.1% (95%CI[4.3-6.0%]) of respondents sought treatment. Most voice problems were resolved within 1 week (53.0%,95%CI[50.9-55.1%]). Females were more likely than males to report a voice problem (14.4% vs. 10.0%,95%CI[13.7-15.1] and [9.3-10.7], respectively). The 17.6 million Americans with long COVID symptoms were more likely to have voice complaints than those without (21.1% vs. 11.6%,95%CI[18.9-23.5%] and [11.1-12.1%], respectively). Lost workdays were not significantly higher for those with voice disorders compared to those without (17.1 vs. 12.9 days,95%CI[12.0-22.1] and [11.0-14.8], respectively).

CONCLUSIONS: Voice problems affect approximately 1 in 8 adults in the U.S. annually, demonstrating an alarming increased prevalence since 2012 using the same survey methodology. Relatively few individuals seek care for their voice problem, despite significant self-reported impact. Further study is required regarding the impact of COVID and changes in voice use patterns on voice disorders.

LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3713-3718, 2024.}, } @article {pmid38523497, year = {2024}, author = {Chatys-Bogacka, Ż and Mazurkiewicz, I and Słowik, J and Słowik, A and Drabik, L and Wnuk, M}, title = {Association between brain fog, cardiac injury, and quality of life at work after hospitalization due to COVID-19.}, journal = {Medycyna pracy}, volume = {75}, number = {1}, pages = {3-17}, doi = {10.13075/mp.5893.01428}, pmid = {38523497}, issn = {2353-1339}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; Quality of Life ; Retrospective Studies ; SARS-CoV-2 ; Hospitalization ; }, abstract = {BACKGROUND: To evaluate incidence and search for possible predictors of brain fog and quality of life at work (QoL-W) among low-to-moderate risk subjects previously hospitalized due to COVID-19.

MATERIAL AND METHODS: Participants aged ≥18 retrospectively reported 8 brain fog symptoms pre-COVID-19, at 0-4, 4-12 and >12 weeks post-infection via validated clinical questionnaire. The QoL-W was assessed with a 4-point Likert scale where 0, 1, 2, and 3 meant no, mild, moderate, and severe impairment in performing activities at work, respectively. Data on age, sex, comorbidities, and laboratory results (including first in-hospital high-sensitivity cardiac troponin I [hs-cTnI] measurement) were gathered.

RESULTS: The study included 181 hospitalized subjects (age Me = 57 years), 37.02% women. Most had low disease severity (Modified Early Warning Score = 1, 77.90%) and low comorbidity (Charlson Comorbidity Index 0: 28.72%, 1-2: 34.09%), with no intensive care unit treatment needed. COVID-19 led to almost 3-fold increased brain fog symptoms, with incidence of 58.56%, 53.59%, and 49.17% within 4, 4-12, and >12 weeks, respectively (p < 0.001). First in-hospital hs-cTnI levels were 47.3% higher in participants who later presented with brain fog at median follow-up of 26.7 weeks since the diagnosis of the SARS-CoV-2 infection. Individuals who experienced at least one brain fog symptom at follow-up, had elevated hs-cTnI, less often presented with atrial fibrillation, and used anticoagulants during initial hospitalization due to COVID-19. The Hs-cTnI >11.90 ng/l predicted brain fog symptoms in multivariable model. COVID-19 was associated with 3.6‑fold, 3.0‑fold, and 2.4-fold QoL-W deterioration within 4, 4-12, and >12 weeks post-infection (p < 0.05). Subjects with QoL-W decline >12 weeks were younger, mostly women, had more brain fog symptoms, and higher platelet counts. Multivariable models with self-reported brain fog symptoms (responding coherently and recalling recent information), age, and sex exhibited good discriminatory power for QoL-W impairment (area under the receiver operating characteristic curve 0.846, 95% CI: 0.780-0.912).

CONCLUSIONS: This study highlighted that in non-high-risk subjects hospitalized during the first 2 pandemic's waves: 1) brain fog was common, affecting nearly half of individuals, and impacting QoL-W >12 weeks after initial infection, 2) after 3 months of COVID-19 onset, the decline in QoL-W was primarily attributed to brain fog symptoms rather than demographic factors, health conditions, admission status, and laboratory findings, 3) components of brain fog, such as answering in an understandable way or recalling new information increased the likelihood of significantly lower QoL-W up to tenfold, 4) biochemical indicators, such as the first hs-cTnI level, might predict the risk of experiencing brain fog symptoms and indirectly decreased QoL-W >12 weeks after COVID-19 onset. Occupational medicine practitioners should pay particular attention to younger and female subjects after COVID-19 complaining of problems with answering questions in understandable way or recalling new information as they have an increased risk of QoL-W impairment. Med Pr Work Health Saf. 2024;75(1):3-17.}, } @article {pmid38523393, year = {2024}, author = {Cem, E and Özenen, GG and Bayram, N and Devrim, İ}, title = {Response to `Rehospitalization indications of children hospitalized for COVID-19 infections and long COVID`.}, journal = {The Turkish journal of pediatrics}, volume = {66}, number = {1}, pages = {145-146}, doi = {10.24953/turkjped.2023.800}, pmid = {38523393}, issn = {2791-6421}, mesh = {Child ; Humans ; *Patient Readmission ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Hospitalization ; Risk Factors ; }, } @article {pmid38523392, year = {2024}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Rehospitalization indications of children hospitalized for COVID-19 infections and long COVID.}, journal = {The Turkish journal of pediatrics}, volume = {66}, number = {1}, pages = {143-144}, doi = {10.24953/turkjped.2023.670}, pmid = {38523392}, issn = {2791-6421}, mesh = {Child ; Humans ; *Patient Readmission ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Hospitalization ; Risk Factors ; }, } @article {pmid38523179, year = {2024}, author = {Okazaki, E and Barion, BG and da Rocha, TRF and Di Giacomo, G and Ho, YL and Rothschild, C and Fatobene, G and de Carvalho Moraes, BDG and Stefanello, B and Villaça, PR and Rocha, VG and Orsi, FA}, title = {Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.}, journal = {Journal of thrombosis and thrombolysis}, volume = {57}, number = {4}, pages = {721-729}, pmid = {38523179}, issn = {1573-742X}, support = {88887.679326/2023-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 038018/2021//Ministério da Saúde/ ; }, mesh = {Humans ; *COVID-19 ; Fibrinolysis ; Plasminogen Activator Inhibitor 1/pharmacology ; *Antifibrinolytic Agents ; Post-Acute COVID-19 Syndrome ; *Thrombophilia ; }, abstract = {Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10 days, 11-15 days, 16-20 days, 21-25 days, and 26-30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.}, } @article {pmid38522030, year = {2024}, author = {Fracella, M and Mancino, E and Nenna, R and Virgillito, C and Frasca, F and D'Auria, A and Sorrentino, L and Petrarca, L and La Regina, D and Matera, L and Di Mattia, G and Caputo, B and Antonelli, G and Pierangeli, A and Viscidi, RP and Midulla, F and Scagnolari, C}, title = {Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID.}, journal = {European journal of immunology}, volume = {54}, number = {5}, pages = {e2350682}, doi = {10.1002/eji.202350682}, pmid = {38522030}, issn = {1521-4141}, support = {//EU/ ; PE00000007//NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; //Sapienza University of Rome/ ; RM1221814ED155C3//Progetti Ricerca-Progetti Medi/ ; }, mesh = {Humans ; Child ; Adolescent ; *Interferon Type I/metabolism/immunology/genetics ; Male ; *COVID-19/immunology ; Female ; *Signal Transduction/immunology ; *SARS-CoV-2/immunology ; Immunity, Innate ; Age Factors ; Post-Acute COVID-19 Syndrome ; RNA, Messenger/genetics ; }, abstract = {SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/β/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-β, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-β, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.}, } @article {pmid38521555, year = {2024}, author = {Szanyi, J and Howe, S and Blakely, T}, title = {The importance of reporting accurate estimates of long COVID prevalence.}, journal = {Lancet (London, England)}, volume = {403}, number = {10432}, pages = {1136-1137}, doi = {10.1016/S0140-6736(23)01120-0}, pmid = {38521555}, issn = {1474-547X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; }, } @article {pmid38521195, year = {2024}, author = {Alaedini, A and Lightman, S and Wormser, GP}, title = {Is Low Cortisol a Marker of Long COVID?.}, journal = {The American journal of medicine}, volume = {137}, number = {7}, pages = {564-565}, doi = {10.1016/j.amjmed.2024.03.013}, pmid = {38521195}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/blood/diagnosis ; *Hydrocortisone/blood ; *Biomarkers/blood ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38520748, year = {2024}, author = {Amodeo, A and Persani, L and Bonomi, M and Cangiano, B}, title = {Use of testosterone replacement therapy to treat long-COVID-related hypogonadism.}, journal = {Endocrinology, diabetes & metabolism case reports}, volume = {2024}, number = {1}, pages = {}, pmid = {38520748}, issn = {2052-0573}, abstract = {SUMMARY: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can impair pituitary-gonadal axis and a higher prevalence of hypogonadism in post-coronavirus disease 2019 (COVID-19) patients compared with the general population has been highlighted. Here we report the first case of a patient affected with a long-COVID syndrome leading to hypogonadism and treated with testosterone replacement therapy (TRT) and its effects on clinical and quality of life (QoL) outcomes. We encountered a 62-year-old man who had been diagnosed with hypogonadotropic hypogonadism about 2 months after recovery from COVID-19 underwent a complete physical examination, general and hormonal blood tests, and self-reported questionnaires administration before and after starting TRT. Following the TRT, both serum testosterone level and hypogonadism-related symptoms were improved, but poor effects occurred on general and neuropsychiatric symptoms and QoL. Therefore, hypogonadism does not appear to be the cause of neurocognitive symptoms, but rather a part of the long-COVID syndrome; as a consequence, starting TRT can improve the hypogonadism-related symptoms without clear benefits on general clinical condition and QoL, which are probably related to the long-COVID itself. Longer follow-up might clarify whether post-COVID hypogonadism is a transient condition that can revert as the patient recovers from long-COVID syndrome.

LEARNING POINTS: Hypogonadism is more prevalent in post-COVID-19 patients compared with the general population. In these patients, hypogonadism may be part of long-COVID syndrome, and it is still unclear whether it is a transient condition or a permanent impairment of gonadal function. Testosterone replacement therapy has positive effects on hypogonadism-related clinic without clear benefits on general symptomatology and quality of life, which are more likely related to the long-COVID itself.}, } @article {pmid38520687, year = {2024}, author = {Dey, M and Mishra, B and Mohapatra, PR and Mohakud, S and Behera, B}, title = {Microbiological profile of long COVID and associated clinical and radiological findings: a prospective cross-sectional study.}, journal = {Laboratory medicine}, volume = {55}, number = {5}, pages = {595-601}, doi = {10.1093/labmed/lmae010}, pmid = {38520687}, issn = {1943-7730}, mesh = {Humans ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Prospective Studies ; *COVID-19/epidemiology/diagnosis ; Aged ; Adult ; SARS-CoV-2 ; Nasopharynx/virology/microbiology ; Bacterial Infections/epidemiology/diagnosis ; Post-Acute COVID-19 Syndrome ; Sputum/microbiology/virology ; Aged, 80 and over ; }, abstract = {OBJECTIVE: To study the frequency of microbiological etiology of respiratory infections in patients with long COVID and their associated clinical and radiological findings.

METHODS: Nasopharyngeal swabs and sputum specimens were collected from 97 patients with respiratory illness stemming from long COVID. The specimens were assessed for their microbiological profile (bacteria and virus) and their association with the overall clinical and radiological picture.

RESULTS: In total, 23 (24%) patients with long COVID had viral infection (n = 12), bacterial infection (n = 9), or coinfection (n = 2). Microorganisms were detected at significantly higher rates in hospitalized patients, patients with moderate COVID-19, and patients with asthma (P < .05). Tachycardia (65%) was the most common symptom at presentation. A statistically significant number of patients with long COVID who had viral infection presented with cough and myalgia; and a statistically significant number of patients with long COVID who had bacterial infection presented with productive coughing (P < .05). Post-COVID fibrotic changes were found in 61% of cohort patients (31/51).

CONCLUSION: A decreasing trend of respiratory pathogens (enveloped viruses and bacteria) was found in long COVID. An analysis including a larger group of viral- or bacterial-infected patients with long COVID is needed to obtain high-level evidence on the presenting symptoms (cough, myalgia) and their association with the underlying comorbidities and severity.}, } @article {pmid38520594, year = {2024}, author = {Gupta, A and Comfort, B and Young, K and Montgomery, R}, title = {A pilot study to assess blood-brain barrier permeability in long COVID.}, journal = {Brain imaging and behavior}, volume = {18}, number = {4}, pages = {830-834}, pmid = {38520594}, issn = {1931-7565}, support = {K23 AG055666/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Blood-Brain Barrier/diagnostic imaging ; Pilot Projects ; Male ; Female ; *COVID-19/complications/diagnostic imaging ; Aged ; Case-Control Studies ; *Tomography, Emission-Computed, Single-Photon/methods ; Middle Aged ; Brain/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; Permeability ; Cognitive Dysfunction/diagnostic imaging/physiopathology ; Memory Disorders/diagnostic imaging/etiology/physiopathology ; }, abstract = {The etiology of brain fog associated with long COVID is not clear. Based on some preliminary work, disruption of the blood-brain barrier has been hypothesized, but has not been tested in patients with long COVID. In this case-control pilot study, we evaluated blood-brain barrier permeability in patients with long COVID and subjective memory loss or brain fog. We used 99 m Technetium diethylenetriaminepentaacetic acid single-photon emission computed tomography (SPECT) to measure blood-brain barrier permeability and a telephone assessment (T-cog) to measure cognitive function. The blood-brain barrier permeability was quantified via SPECT standard uptake value (SUV). We assessed the blood-brain barrier permeability in 14 long COVID patients and 10 control participants without subjective cognitive impairment or brain fog. Participants in the two groups were similar in age. The long COVID group had more comorbidities compared to the control group. There was no difference in the SUVs in the long COVID (0.22 ± 0.12) vs the control (0.17 ± 0.04) group. There was no difference in the T-cog results in the two groups either. We found no evidence of a difference in blood-brain permeability in patients with long COVID when compared to controls without a known history of COVID-19 infection. Larger studies are needed to confirm these findings.}, } @article {pmid38520374, year = {2024}, author = {Garmoe, W and Rao, K and Gorter, B and Kantor, R}, title = {Neurocognitive Impairment in Post-COVID-19 Condition in Adults: Narrative Review of the Current Literature.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {39}, number = {3}, pages = {276-289}, doi = {10.1093/arclin/acae017}, pmid = {38520374}, issn = {1873-5843}, mesh = {Adult ; Humans ; *Cognitive Dysfunction/etiology ; COVID-19/complications ; SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome/physiopathology ; Neuropsychology ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 virus has, up to the time of this article, resulted in >770 million cases of COVID-19 illness worldwide, and approximately 7 million deaths, including >1.1 million in the United States. Although defined as a respiratory virus, early in the pandemic, it became apparent that considerable numbers of people recovering from COVID-19 illness experienced persistence or new onset of multi-system health problems, including neurologic and cognitive and behavioral health concerns. Persistent multi-system health problems are defined as Post-COVID-19 Condition (PCC), Post-Acute Sequelae of COVID-19, or Long COVID. A significant number of those with PCC report cognitive problems. This paper reviews the current state of scientific knowledge on persisting cognitive symptoms in adults following COVID-19 illness. A brief history is provided of the emergence of concerns about persisting cognitive problems following COVID-19 illness and the definition of PCC. Methodologic factors that complicate clear understanding of PCC are reviewed. The review then examines research on patterns of cognitive impairment that have been found, factors that may contribute to increased risk, behavioral health variables, and interventions being used to ameliorate persisting symptoms. Finally, recommendations are made about ways neuropsychologists can improve the quality of existing research.}, } @article {pmid38518814, year = {2024}, author = {McClelland, AC and Benitez, SJ and Burns, J}, title = {COVID-19 Neuroimaging Update: Pathophysiology, Acute Findings, and Post-Acute Developments.}, journal = {Seminars in ultrasound, CT, and MR}, volume = {45}, number = {4}, pages = {318-331}, doi = {10.1053/j.sult.2024.03.003}, pmid = {38518814}, issn = {1558-5034}, mesh = {Humans ; *COVID-19/diagnostic imaging/physiopathology ; *Neuroimaging/methods ; *SARS-CoV-2 ; Brain/diagnostic imaging/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has prominent effects on the nervous system with important manifestations on neuroimaging. In this review, we discuss the neuroimaging appearance of acute COVID-19 that became evident during the early stages of the pandemic. We highlight the underlying pathophysiology mediating nervous system effects and neuroimaging appearances including systemic inflammatory response such as cytokine storm, coagulopathy, and para/post-infections immune mediated phenomena. We also discuss the nervous system manifestations of COVID-19 and the role of imaging as the pandemic has evolved over time, including related to the development of vaccines and the emergence of post-acute sequalae such as long COVID.}, } @article {pmid38518681, year = {2024}, author = {Chakraborty, C and Bhattacharya, M and Alshammari, A and Albekairi, TH}, title = {Blueprint of differentially expressed genes reveals the dynamic gene expression landscape and the gender biases in long COVID.}, journal = {Journal of infection and public health}, volume = {17}, number = {5}, pages = {748-766}, doi = {10.1016/j.jiph.2024.02.018}, pmid = {38518681}, issn = {1876-035X}, mesh = {Humans ; Male ; Female ; *Gene Expression Profiling ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Gene Expression ; Bias ; }, abstract = {BACKGROUND: Long COVID has appeared as a significant global health issue and is an extra burden to the healthcare system. It affects a considerable number of people throughout the globe. However, substantial research gaps have been noted in understanding the mechanism and genomic landscape during the long COVID infection. A study has aimed to identify the differentially expressed genes (DEGs) in long COVID patients to fill the gap.

METHODS: We used the RNA-seq GEO dataset acquired through the GPL20301 Illumina HiSeq 4000 platform. The dataset contains 36 human samples derived from PBMC (Peripheral blood mononuclear cells). Thirty-six human samples contain 13 non-long COVID individuals' samples and 23 long COVID individuals' samples, considered the first direction analysis. Here, we performed two-direction analyses. In the second direction analysis, we divided the dataset gender-wise into four groups: the non-long COVID male group, the long COVID male group, the non-long COVID female group, and the long COVID female group.

RESULTS: In the first analysis, we found no gene expression. In the second analysis, we identified 250 DEGs. During the DEG profile analysis of the non-long COVID male group and the long COVID male group, we found three upregulated genes: IGHG2, IGHG4, and MIR8071-2. Similarly, the analysis of the non-long COVID female group and the long COVID female group reveals eight top-ranking genes. It also indicates the gender biases of differentially expressed genes among long COVID individuals. We found several DEGs involved in PPI and co-expression network formation. Similarly, cluster enrichment and gene list enrichment analysis were performed, suggesting several genes are involved in different biological pathways or processes.

CONCLUSIONS: This study will help better understand the gene expression landscape in long COVID. However, it might help the discovery and development of therapeutics for long COVID.}, } @article {pmid38518038, year = {2024}, author = {Kavanagh, KT and Cormier, LE and Pontus, C and Bergman, A and Webley, W}, title = {Long COVID's Impact on Patients, Workers, & Society: A review.}, journal = {Medicine}, volume = {103}, number = {12}, pages = {e37502}, pmid = {38518038}, issn = {1536-5964}, mesh = {Adult ; Child ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Disease Outbreaks ; }, abstract = {The incidence of long COVID in adult survivors of an acute SARS-CoV-2 infection is approximately 11%. Of those afflicted, 26% have difficulty with day-to-day activities. The majority of long COIVD cases occur after mild or asymptomatic acute infection. Children can spread SARS-CoV-2 infections and can also develop long-term neurological, endocrine (type I diabetes), and immunological sequelae. Immunological hypofunction is exemplified by the recent large outbreaks of respiratory syncytial virus and streptococcal infections. Neurological manifestations are associated with anatomical brain damage demonstrated on brain scans and autopsy studies. The prefrontal cortex is particularly susceptible. Common symptoms include brain fog, memory loss, executive dysfunction, and personality changes. The impact on society has been profound. Fewer than half of previously employed adults who develop long COVID are working full-time, and 42% of patients reported food insecurity and 20% reported difficulties paying rent. Vaccination not only helps prevent severe COVID-19, but numerous studies have found beneficial effects in preventing and mitigating long COVID. There is also evidence that vaccination after an acute infection can lessen the symptoms of long COVID. Physical and occupational therapy can also help patients regain function, but the approach must be "low and slow." Too much physical or mental activity can result in post-exertional malaise and set back the recovery process by days or weeks. The complexity of long COVID presentations coupled with rampant organized disinformation, have caused significant segments of the public to ignore sound public health advice. Further research is needed regarding treatment and effective public communication.}, } @article {pmid38516229, year = {2023}, author = {da Silveira, AD and Scolari, FL and Saadi, MP and Brahmbhatt, DH and Milani, M and Milani, JGPO and Junior, GC and Sartor, ITS and Zavaglia, GO and Tonini, ML and da Costa, MSC and Scotta, MC and Stein, RT and Rosa, RG}, title = {Long-term reduced functional capacity and quality of life in hospitalized COVID-19 patients.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1289454}, pmid = {38516229}, issn = {2296-858X}, abstract = {BACKGROUND: Persistent symptoms and exercise intolerance have been reported after COVID-19, even months after the acute disease. Although, the long-term impact on exercise capacity and health-related quality of life (HRQoL) is still unclear.

RESEARCH QUESTION: To assess the long-term functional capacity and HRQoL in patients hospitalized due to COVID-19.

STUDY DESIGN AND METHODS: This is a prospective cohort study, conducted at two centers in Brazil, that included post-discharge COVID-19 patients and paired controls. The cohort was paired by age, sex, body mass index and comorbidities, using propensity score matching in a 1:3 ratio. Patients were eligible if signs or symptoms suggestive of COVID-19 and pulmonary involvement on chest computed tomography. All patients underwent cardiopulmonary exercise testing (CPET) and a HRQoL questionnaire (SF-36) 6 months after the COVID-19. The main outcome was the percentage of predicted peak oxygen consumption (ppVO2). Secondary outcomes included other CPET measures and HRQoL.

RESULTS: The study sample comprised 47 post-discharge COVID-19 patients and 141 healthy controls. The mean age of COVID-19 patients was 54 ± 14 years, with 19 (40%) females, and a mean body mass index of 31 kg/m[2] (SD, 6). The median follow-up was 7 months (IQR, 6.5-8.0) after hospital discharge. PpVO2 in COVID-19 patients was lower than in controls (83% vs. 95%, p = 0.002) with an effect size of 0.38 ([95%CI], 0.04-0.70). Mean peak VO2 (22 vs. 25 mL/kg/min, p = 0.04) and OUES (2,122 vs. 2,380, p = 0.027) were also reduced in the COVID-19 patients in comparison to controls. Dysfunctional breathing (DB) was present in 51%. HRQoL was significantly reduced in post COVID patients and positively correlated to peak exercise capacity.

INTERPRETATION: Hospitalized COVID-19 patients presented, 7 months after discharge, with a reduction in functional capacity and HRQoL when compared to historical controls. HRQoL were reduced and correlated with the reduced peak VO2 in our population.}, } @article {pmid38515584, year = {2024}, author = {Koch, CA}, title = {Long Covid: Hormone Imbalances and/or Rather Complex Immune Dysregulations?.}, journal = {Journal of the Endocrine Society}, volume = {8}, number = {5}, pages = {bvae043}, pmid = {38515584}, issn = {2472-1972}, } @article {pmid38514769, year = {2024}, author = {Wang, Y and Su, B and Xie, J and Garcia-Rizo, C and Prieto-Alhambra, D}, title = {Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population.}, journal = {Nature human behaviour}, volume = {8}, number = {6}, pages = {1076-1087}, pmid = {38514769}, issn = {2397-3374}, mesh = {Humans ; *COVID-19/prevention & control/epidemiology/psychology ; United Kingdom/epidemiology ; *Mental Disorders/epidemiology/drug therapy ; Male ; Female ; Middle Aged ; *Psychotropic Drugs/therapeutic use ; Adult ; Aged ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Drug Prescriptions/statistics & numerical data ; Cohort Studies ; }, abstract = {Despite evidence indicating increased risk of psychiatric issues among COVID-19 survivors, questions persist about long-term mental health outcomes and the protective effect of vaccination. Using UK Biobank data, three cohorts were constructed: SARS-CoV-2 infection (n = 26,101), contemporary control with no evidence of infection (n = 380,337) and historical control predating the pandemic (n = 390,621). Compared with contemporary controls, infected participants had higher subsequent risks of incident mental health at 1 year (hazard ratio (HR): 1.54, 95% CI 1.42-1.67; P = 1.70 × 10[-24]; difference in incidence rate: 27.36, 95% CI 21.16-34.10 per 1,000 person-years), including psychotic, mood, anxiety, alcohol use and sleep disorders, and prescriptions for antipsychotics, antidepressants, benzodiazepines, mood stabilizers and opioids. Risks were higher for hospitalized individuals (2.17, 1.70-2.78; P = 5.80 × 10[-10]) than those not hospitalized (1.41, 1.30-1.53; P = 1.46 × 10[-16]), and were reduced in fully vaccinated people (0.97, 0.80-1.19; P = 0.799) compared with non-vaccinated or partially vaccinated individuals (1.64, 1.49-1.79; P = 4.95 × 10[-26]). Breakthrough infections showed similar risk of psychiatric diagnosis (0.91, 0.78-1.07; P = 0.278) but increased prescription risk (1.42, 1.00-2.02; P = 0.053) compared with uninfected controls. Early identification and treatment of psychiatric disorders in COVID-19 survivors, especially those severely affected or unvaccinated, should be a priority in the management of long COVID. With the accumulation of breakthrough infections in the post-pandemic era, the findings highlight the need for continued optimization of strategies to foster resilience and prevent escalation of subclinical mental health symptoms to severe disorders.}, } @article {pmid38510801, year = {2024}, author = {Allwang, C and Frank, T and Bruckmann, P and Dinkel, A and Binneboese, M and Wallis, H and Elgner, M and Giel, KE and Schurr, M and Gündel, H and Wedekind, L and Kuhn, J and Lahmann, C and Müller, AM and Beckmann, P and Massag, J and Mikolajczyk, R and Junne, F}, title = {Addressing psychosocial needs in patients with Long-COVID (PsyLoCo-Study): study protocol of a pilot-study of a specialized modular intervention.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1305691}, pmid = {38510801}, issn = {1664-0640}, abstract = {INTRODUCTION: After an acute infection with the corona virus 10-20% of those affected suffer from ongoing or new symptoms. A causal therapy for the phenomenon known as Long/Post-COVID is still lacking and specific therapies addressing psychosocial needs of these patients are imperatively needed. The aim of the PsyLoCo-study is developing and piloting a psychotherapeutic manual, which addresses Long/Post-COVID-related psychosocial needs and supports in coping with persistent bodily symptoms as well as depressive or anxiety symptoms.

METHODS AND ANALYSIS: This pilot trial implements a multi-centre, 2-arm (N=120; allocation ratio: 1:1), parallel group, randomised controlled design. The pilot trial is designed to test the feasibility and estimate the effect of 1) a 12-session psychotherapeutic intervention compared to 2) a wait-list control condition on psychosocial needs as well as bodily and affective symptoms in patients suffering from Long/Post-COVID. The intervention uses an integrative, manualized, psychotherapeutic approach. The primary study outcome is health-related quality of life. Outcome variables will be assessed at three timepoints, pre-intervention (t1), post-intervention (t2) and three months after completed intervention (t3). To determine the primary outcome, changes from t1 to t2 are examined. The analysis will be used for the planning of the RCT to test the efficacy of the developed intervention.

DISCUSSION: The pilot study will evaluate a 12-session treatment manual for Long/Post-COVID sufferers and the therapy components it contains. The analysis will provide insights into the extent to which psychotherapeutic treatment approaches improve the symptoms of Long/Post-COVID sufferers. The treatment manual is designed to be carried out by psychotherapists as well as people with basic training in psychotherapeutic techniques. This approach was chosen to enable a larger number of practitioners to provide therapeutic support for Long/Post-COVID patients. After completion of the pilot study, it is planned to follow up with a randomized controlled study and to develop a treatment guideline for general practitioners and interested specialists.

TRIAL REGISTRATION: The pilot trial has been registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien; Trial-ID: DRKS00030866; URL: https://drks.de/search/de/trial/DRKS00030866) on March 7, 2023.}, } @article {pmid38510743, year = {2024}, author = {Gonjilashvili, A and Tatishvili, S}, title = {The interplay between Sars-Cov-2 infection related cardiovascular diseases and depression. Common mechanisms, shared symptoms.}, journal = {American heart journal plus : cardiology research and practice}, volume = {38}, number = {}, pages = {100364}, pmid = {38510743}, issn = {2666-6022}, abstract = {In 2020 the World Health organization announced a pandemic due to the outbreak of the Coronavirus disease 19. Pneumonia was the most common manifestation of the Sars-Cov-2 infection, however, clinical papers describe Sars-Cov-2 associated cardiovascular pathologies, such as ACS, myopericarditis, cardiomyopathies, dysrhythmias, as leading causes of increased morbidity and mortality. The short and long term prognosis of Sars-Cov-2-related cardiovascular diseases was defined not only by the disease severity itself but also by associated conditions and complications, among which mental health issues (stress, depression and anxiety) have a negative impact. The interplay between Sars-Cov-2 infection, cardiovascular disease and depression may be explained by hyperinflammation, unhealthy lifestyle and inter-organ communication, mediated by extracellular vesicles (EV) and non-coding MicroRNA (miRNA). The long Covid syndrome is characterized with orthostatic hypotension, impaired cardiac and cerebral perfusion, postural orthostatic tachycardia syndrome (POTS), syncope, chest pain, dyspnea, palpitation, chronic fatigue syndrome, 'brain fog', memory, cognitive and sleep difficulties, depression and anxiety. From a clinical point of view these symptoms may be considered as common symptoms representing not only a cardiac but also a neurological/psychiatric problem. Consequently assessment of these symptoms are of paramount importance. Due to their complexity, management of these patients requires multidisciplinary care.}, } @article {pmid38510249, year = {2024}, author = {Boyarchuk, O and Perestiuk, V and Kosovska, T and Volianska, L}, title = {Coagulation profile in hospitalized children with COVID-19: pediatric age dependency and its impact on long COVID development.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1363410}, pmid = {38510249}, issn = {1664-3224}, mesh = {Humans ; Female ; Child ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Child, Hospitalized ; Cohort Studies ; Inflammation/complications ; Prospective Studies ; *Thrombosis/epidemiology/complications ; *Blood Coagulation Disorders/etiology ; }, abstract = {INTRODUCTION: Pulmonary endotheliopathy and microvascular immunothrombosis play a key role in acute COVID-19. Moreover, persistent endotheliopathy and heightened coagulability frequently occur in individuals recovering from COVID-19, suggesting the intriguing possibility of their role in the development of long COVID. The aim of our study was to investigate the coagulation profile in patients with COVID-19 based on age and their role in the development of long COVID.

METHODS: We conducted a prospective single-center cohort study from September 2022 to August 2023. The study involved 190 patients younger than 18 years who were hospitalized at the Ternopil City Children's Hospital, Ukraine due to COVID-19. Patients underwent determination of coagulation profile in addition to the general clinical examination. After discharge from the hospital, patients were monitored for the presence of long COVID symptoms. Among the 157 participants who consented for follow-up, 62 patients (39.5%) had long COVID symptoms according to the WHO definition, while the rest (95 patients) did not have symptoms of long COVID (fully recovered).

RESULTS: The study revealed the normal count of platelets in the majority of patients (86.8%), whereas abnormalities in the coagulation profile were revealed in 94.5% of children with COVID-19, and these changes were age-dependent. The patients were mostly presented with increased activated partial thromboplastin time (69.1%), prothrombin time (PT) (39.8%) and D-dimer (45.0%). There was no significant difference between the median of platelet levels and coagulation profile indicators between the groups with long COVID and recovered. Among children who developed persistent long COVID symptoms there was a statistically higher percentage of abnormal PT values (53% versus 36.1%, p=0.0432), with no significant differences in other coagulation profile indicators. Abnormal PT along with female gender, comorbidities, especially allergic pathology, nutritional disorder, including obesity, were determined as potential risk factors of the long COVID development (Odds ratio - 2.0611; 95% 1.0179-4.1737, p=0.0445).

CONCLUSIONS: The study highlights the need for more extensive research into the coagulation profiles of pediatric populations, considering age-specific factors. This could enhance our understanding of thromboinflammation in COVID-19 and its potential contribution to the development of persistent symptoms.}, } @article {pmid38509608, year = {2024}, author = {Franke, C and Raeder, V and Boesl, F and Bremer, B and Adam, LC and Gerhard, A and Eckert, I and Quitschau, A and Pohrt, A and Burock, S and Bruckert, L and Scheibenbogen, C and Prüß, H and Audebert, HJ}, title = {Randomized controlled double-blind trial of methylprednisolone versus placebo in patients with post-COVID-19 syndrome and cognitive deficits: study protocol of the post-corona-virus immune treatment (PoCoVIT) trial.}, journal = {Neurological research and practice}, volume = {6}, number = {1}, pages = {16}, pmid = {38509608}, issn = {2524-3489}, support = {01EP2201//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie/ ; }, abstract = {INTRODUCTION: Post-COVID-19 Syndrome (PCS) includes neurological manifestations, especially fatigue and cognitive deficits. Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation are discussed as potential pathophysiological mechanisms. The post-corona-virus immune treatment (PoCoVIT) trial is a phase 2a randomized, controlled, double-blind trial designed to evaluate the effect of methylprednisolone versus placebo on cognitive impairment in PCS. This trial is designed based on the hypothesised autoimmunological pathogenesis and positive aberrations, employing a series of off-label applications.

METHODS: Recruitment criteria include a diagnosis of PCS, a minimum age of 18 years and self-reported cognitive deficits at screening. A total of 418 participants will be randomly assigned to either verum or placebo intervention in the first phase of the trial. The trial will consist of a first trial phase intervention with methylprednisolone versus placebo for six weeks, followed by a six-week treatment interruption period. Subsequently, an open second phase will offer methylprednisolone to all participants for six weeks. Outpatient follow-up visits will take place two weeks after each trial medication cessation. The third and final follow-up, at week 52, will be conducted through a telephone interview. The primary outcome measures an intra-patient change of 15 or more points in the memory satisfaction subscale of the Multifactorial Memory Questionnaire (MMQ) from baseline to follow-up 1 (week 8). Key secondary outcomes include long-term intra-patient changes in memory satisfaction from baseline to follow-up 2 (week 20), changes in other MMQ subscales (follow-up 1 and 2), and changes in neuropsychological and cognitive scores, along with assessments through questionnaires focusing on quality of life, fatigue, and mood over the same periods. Exploratory outcomes involve molecular biomarkers variations in serum and cerebrospinal fluid, as well as structural and functional brain magnetic resonance imaging (MRI) parameters changes related to cognition.

PERSPECTIVE: This trial aims to contribute novel evidence for treating patients with PCS, with a primary focus on those manifesting cognitive deficits. By doing so, it may enhance comprehension of the underlying pathophysiological mechanisms, thereby facilitating biomarker research to advance our understanding and treatment of patients with PCS.}, } @article {pmid38509550, year = {2024}, author = {Zeraatkhah, H and Alavi, NM and Ziabakhsh, H and Mahdaviasl, Z}, title = {Prevalence and characters of post-acute COVID-19 syndrome in healthcare workers in Kashan/Iran 2023: a cross-sectional study.}, journal = {BMC nursing}, volume = {23}, number = {1}, pages = {186}, pmid = {38509550}, issn = {1472-6955}, support = {401153//Kashan University of Medical Sciences/ ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome that is called long COVID-19 consists of the symptoms that last more than 12 weeks with no other explanation. The present study aimed to determine the prevalence, frequency of symptoms, and risk factors of long COVID-19 in the healthcare workers (HCWs) of a selected hospital in Kashan/Iran in 2023.

METHODS: A total of 350 HCWs with a history of COVID-19 infection were randomly recruited to the study from February to May 2023. Participants completed a questionnaire including demographic characteristics, information related to COVID-19 infection, underlying diseases, and a checklist of long COVID-19 symptoms. Mann‒Whitney U test, chi-square test, T‒tests, and binary logistic regression were used for data analysis by SPSS 16.

RESULTS: The results showed that 75.7% of HCWs experienced symptoms of long COVID-19. The most common symptoms were fatigue (53.1%), cough (43.1%) and muscle weakness (37.1%). In bivariate analysis job title, body mass index (BMI), frequency and number of symptoms of COVID-19 infection, preexisting disease, tobacco use, age, and years of experience showed a significant statistical association with long COVID-19. In binary logistic regression the number of symptoms during COVID-19 infection, nursing occupation, use of corticosteroids, and symptoms of dyspnea and loss of taste could explain the occurrence of long COVID-19.

CONCLUSION: The long COVID-19 is a prevalent condition among HCWs especially nurses. Symptoms of long COVID-19 such as fatigue and cough can persists over time. This chronic condition has significant associations with different clinical risk factors.}, } @article {pmid38509295, year = {2024}, author = {López Lloreda, C}, title = {COVID's toll on the brain: new clues emerge.}, journal = {Nature}, volume = {628}, number = {8006}, pages = {20}, pmid = {38509295}, issn = {1476-4687}, mesh = {Mental Fatigue ; *SARS-CoV-2/metabolism/pathogenicity ; *Neuroinflammatory Diseases/etiology/pathology/virology ; Humans ; *Blood-Brain Barrier/pathology/virology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/pathology/virology ; }, } @article {pmid38508863, year = {2024}, author = {Woldegiorgis, M and Cadby, G and Ngeh, S and Korda, RJ and Armstrong, PK and Maticevic, J and Knight, P and Jardine, A and Bloomfield, LE and Effler, PV}, title = {Long COVID in a highly vaccinated but largely unexposed Australian population following the 2022 SARS-CoV-2 Omicron wave: a cross-sectional survey.}, journal = {The Medical journal of Australia}, volume = {220}, number = {6}, pages = {323-330}, doi = {10.5694/mja2.52256}, pmid = {38508863}, issn = {1326-5377}, mesh = {Adult ; Male ; Female ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; COVID-19 Vaccines ; Australia/epidemiology ; *COVID-19/epidemiology ; *Australasian People ; }, abstract = {OBJECTIVE: To estimate the prevalence of long COVID among Western Australian adults, a highly vaccinated population whose first major exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was during the 2022 Omicron wave, and to assess its impact on health service use and return to work or study.

STUDY DESIGN: Follow-up survey (completed online or by telephone).

SETTING, PARTICIPANTS: Adult Western Australians surveyed 90 days after positive SARS-CoV-2 test results (polymerase chain reaction or rapid antigen testing) during 16 July - 3 August 2022 who had consented to follow-up contact for research purposes.

MAIN OUTCOME MEASURES: Proportion of respondents with long COVID (ie, reporting new or ongoing symptoms or health problems, 90 days after positive SARS-CoV-2 test result); proportion with long COVID who sought health care for long COVID-related symptoms two to three months after infection; proportion who reported not fully returning to previous work or study because of long COVID-related symptoms.

RESULTS: Of the 70 876 adults with reported SARS-CoV-2 infections, 24 024 consented to contact (33.9%); after exclusions, 22 744 people were invited to complete the survey, of whom 11 697 (51.4%) provided complete responses. Our case definition for long COVID was satisfied by 2130 respondents (18.2%). The risk of long COVID was greater for women (v men: adjusted risk ratio [aRR], 1.5; 95% confidence interval [CI], 1.4-1.6) and for people aged 50-69 years (v 18-29 years: aRR, 1.6; 95% CI, 1.4-1.9) or with pre-existing health conditions (aRR, 1.5; 95% CI, 1.4-1.7), as well as for people who had received two or fewer COVID-19 vaccine doses (v four or more: aRR, 1.4; 95% CI, 1.2-1.8) or three doses (aRR, 1.3; 95% CI, 1.1-1.5). The symptoms most frequently reported by people with long COVID were fatigue (1504, 70.6%) and concentration difficulties (1267, 59.5%). In the month preceding the survey, 814 people had consulted general practitioners (38.2%) and 34 reported being hospitalised (1.6%) with long COVID. Of 1779 respondents with long COVID who had worked or studied before the infection, 318 reported reducing or discontinuing this activity (17.8%).

CONCLUSION: Ninety days after infection with the Omicron SARS-CoV-2 variant, 18.2% of survey respondents reported symptoms consistent with long COVID, of whom 38.7% (7.1% of all survey respondents) sought health care for related health concerns two to three months after the acute infection.}, } @article {pmid38508701, year = {2024}, author = {Rhead, R and Wels, J and Moltrecht, B and Shaw, RJ and Silverwood, R and Zhu, J and Hughes, A and Chaturvedi, N and Demou, E and Katikireddi, SV and Ploubidis, G}, title = {Long COVID and financial outcomes: evidence from four longitudinal population surveys.}, journal = {Journal of epidemiology and community health}, volume = {78}, number = {7}, pages = {458-465}, pmid = {38508701}, issn = {1470-2738}, support = {/ERC_/European Research Council/International ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology/economics ; Male ; Female ; Longitudinal Studies ; Middle Aged ; *SARS-CoV-2 ; Adult ; United Kingdom/epidemiology ; *Post-Acute COVID-19 Syndrome ; Aged ; Pandemics ; Income/statistics & numerical data ; Surveys and Questionnaires ; Young Adult ; Financial Stress/epidemiology ; }, abstract = {BACKGROUND: Long-term sequelae of COVID-19 (long COVID) include muscle weakness, fatigue, breathing difficulties and sleep disturbance over weeks or months. Using UK longitudinal data, we assessed the relationship between long COVID and financial disruption.

METHODS: We estimated associations between long COVID (derived using self-reported length of COVID-19 symptoms) and measures of financial disruption (subjective financial well-being, new benefit claims, changes in household income) by analysing data from four longitudinal population studies, gathered during the first year of the pandemic. We employed modified Poisson regression in a pooled analysis of the four cohorts adjusting for a range of potential confounders, including pre-pandemic (pre-long COVID) factors.

RESULTS: Among the 20 112 observations across four population surveys, 13% reported having COVID-19 with symptoms that impeded their ability to function normally-10.7% had such symptoms for <4 weeks (acute COVID-19), 1.2% had such symptoms for 4-12 weeks (ongoing symptomatic COVID-19) and 0.6% had such symptoms for >12 weeks (post-COVID-19 syndrome). We found that post-COVID-19 syndrome was associated with worse subjective financial well-being (adjusted relative risk ratios (aRRRs)=1.57, 95% CI=1.25, 1.96) and new benefit claims (aRRR=1.79, CI=1.27, 2.53). Associations were broadly similar across sexes and education levels. These results were not meaningfully altered when scaled to represent the population by age.

CONCLUSIONS: Long COVID was associated with financial disruption in the UK. If our findings reflect causal effects, extending employment protection and financial support to people with long COVID may be warranted.}, } @article {pmid38508399, year = {2024}, author = {Schmitz, T and Freuer, D and Goßlau, Y and Warm, TD and Hyhlik-Dürr, A and Linseisen, J and Meisinger, C and Kirchberger, I}, title = {Can inflammatory plasma proteins predict Long COVID or Fatigue severity after SARS-CoV-2 infection?.}, journal = {Virus research}, volume = {344}, number = {}, pages = {199363}, pmid = {38508399}, issn = {1872-7492}, mesh = {Humans ; *COVID-19/blood/immunology ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; *Blood Proteins/analysis ; *Fatigue ; *Severity of Illness Index ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Biomarkers/blood ; }, abstract = {OBJECTIVE: To investigate whether specific immune response plasma proteins can predict an elevated risk of developing Long COVID symptoms or fatigue severity after SARS-CoV-2 infection.

METHODS: This study was based on 257 outpatients with test-confirmed SARS-CoV-2 infection between February 2020 and January 2021. At least 12 weeks after the acute infection, 92 plasma proteins were measured using the Olink Target 96 immune response panel (median time between acute infection and venous blood sampling was 38.8 [IQR: 24.0-48.0] weeks). The presence of Long COVID symptoms and fatigue severity was assessed 115.8 [92.5-118.6] weeks after the acute infection by a follow-up postal survey. Long COVID (yes/no) was defined as having one or more of the following symptoms: fatigue, shortness of breath, concentration or memory problems. The severity of fatigue was assessed using the Fatigue Assessment Scale (FAS). In multivariable-adjusted logistic and linear regression models the associations between each plasma protein (exposure) and Long COVID (yes/no) or severity of fatigue were investigated.

RESULTS: Nine plasma proteins were significantly associated with Long COVID before, but not after adjusting for multiple testing (FDR-adjustment): DFFA, TRIM5, TRIM21, HEXIM1, SRPK2, PRDX5, PIK3AP1, IFNLR1 and HCLS1. Moreover, a total of 10 proteins were significantly associated with severity of fatigue before FDR-adjustment: SRPK2, ITGA6, CLEC4G, HEXIM1, PPP1R9B, PLXNA4, PRDX5, DAPP1, STC1 and HCLS1. Only SRPK2 and ITGA6 remained significantly associated after FDR-adjustment.

CONCLUSIONS: This study demonstrates that certain immune response plasma proteins might play an important role in the pathophysiology of Long COVID and severity of fatigue after SARS-CoV-2 infection.}, } @article {pmid38508059, year = {2024}, author = {Srivastava, A and Nalroad Sundararaj, S and Bhatia, J and Singh Arya, D}, title = {Understanding long COVID myocarditis: A comprehensive review.}, journal = {Cytokine}, volume = {178}, number = {}, pages = {156584}, doi = {10.1016/j.cyto.2024.156584}, pmid = {38508059}, issn = {1096-0023}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Myocarditis/etiology ; *Heart Failure ; *Zika Virus ; *Zika Virus Infection ; }, abstract = {Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.}, } @article {pmid38506451, year = {2024}, author = {Sharma, V}, title = {Recharge the cells to overcome the debilitating symptoms in long-COVID.}, journal = {Journal of postgraduate medicine}, volume = {70}, number = {2}, pages = {73-74}, pmid = {38506451}, issn = {0972-2823}, mesh = {Humans ; *COVID-19 ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38506116, year = {2024}, author = {Khullar, V and Lemmon, B and Acar, O and Abrams, P and Vahabi, B}, title = {Does COVID-19 cause or worsen LUT dysfunction, what are the mechanisms and possible treatments? ICI-RS 2023.}, journal = {Neurourology and urodynamics}, volume = {43}, number = {6}, pages = {1458-1463}, doi = {10.1002/nau.25441}, pmid = {38506116}, issn = {1520-6777}, mesh = {Humans ; *COVID-19/complications/physiopathology ; *Lower Urinary Tract Symptoms/physiopathology/etiology/therapy ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and produced a worldwide pandemic in 2020. There have been 770,875,433 confirmed cases and 6,959,316 attributed deaths worldwide until September 19, 2023. The virus can also affect the lower urinary tract (LUT) leading to bladder inflammation and producing lower urinary tract symptoms (LUTS) in both the acute and chronic phases of disease.

METHODS: At the 2023 meeting of the International Consultation on Incontinence-Research Society (ICI-RS), the literature relating to COVID-19 and bladder dysfunction was reviewed. The LUTS reported, as well as the pathophysiology of these bladder symptoms, were the subject of considerable discussion. A number of different topics were discussed including lower LUTS reported in COVID-19, how SARS-CoV-2 may infect and affect the urinary tract, and proposed mechanisms for how viral infection result in new, worsened, and in some persisting LUTS.

CONCLUSIONS: The workshop discussed the interaction between the virus and the immune system, covering current evidence supporting theories underlying the causes of acute and chronic LUTS related to COVID-19 infection. Research questions for further investigation were suggested and identified.}, } @article {pmid38505990, year = {2024}, author = {Eo, Y and Chang, SJ}, title = {Post-acute COVID-19 syndrome in previously hospitalized patients.}, journal = {Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing}, volume = {56}, number = {4}, pages = {517-530}, doi = {10.1111/jnu.12967}, pmid = {38505990}, issn = {1547-5069}, support = {639//Seoul Nurses Association/ ; }, mesh = {Humans ; Female ; Male ; *COVID-19/psychology/epidemiology ; Cross-Sectional Studies ; *Post-Acute COVID-19 Syndrome ; Middle Aged ; Adult ; *Anxiety/epidemiology ; *Fatigue/epidemiology/etiology ; Hospitalization/statistics & numerical data ; Depression/epidemiology ; Prevalence ; Aged ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: With the prolongation of the COVID-19 pandemic, more individuals are experiencing sequelae after COVID-19 infection, also known as post-acute COVID-19 syndrome (PCS). The aims of this study were to describe the prevalence and characteristics of PCS symptoms such as fatigue, anxiety, and depression and to compare these symptoms according to participant characteristics in patients who had been previously hospitalized due to COVID-19.

DESIGN: A descriptive cross-sectional study design was used.

METHODS: We included 114 individuals who had been hospitalized for COVID-19 and were discharged from the hospital at least 4 weeks before. Symptoms were assessed using the Fatigue Severity Scale, the Hospital Anxiety-Depression Scale, and the PCS symptom questionnaire developed by the authors. We used descriptive statistics, the Student's t-test, the Wilcoxon rank-sum test, and the Kruskal-Wallis test for statistical analyses.

RESULTS: The most prevalent symptoms were anxiety (66.7%), fatigue (64.0%), headache (57.9%), and concentration or memory difficulties (57.9%). Concentration or memory difficulties and sleep disturbances had the highest mean frequency. Concentration or memory difficulties were rated with the highest mean severity, and cough, loss of taste, and muscle and joint pain had the highest mean distress scores. Female participants, individuals hospitalized for more than 2 weeks, individuals discharged more than 9 months ago, unvaccinated patients, and those who tried at least one symptom relief method reported higher symptom distress.

CONCLUSION: The findings of this investigation into the frequency, severity, and distress of symptoms shed light on the identification of post-COVID symptoms in detail. To objectively evaluate and comprehend the symptom trajectories of PCS, prospective studies about the development of symptom assessment tools and studies with a longitudinal design should be conducted.

CLINICAL RELEVANCE: A substantial number of respondents reported numerous symptoms and expressed symptom distress; therefore, the development of nursing interventions and treatments to alleviate PCS symptoms is crucial.}, } @article {pmid38505115, year = {2024}, author = {Gustavson, AM and Patrick, A and Ludescher, M and Tonkin, B and Toonstra, A}, title = {Building and Sustaining Organizational Capacity for the Rehabilitation Profession to Support Long COVID Care.}, journal = {Cardiopulmonary physical therapy journal}, volume = {35}, number = {1}, pages = {2-6}, pmid = {38505115}, issn = {1541-7891}, support = {K12 HS026379/HS/AHRQ HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; }, } @article {pmid38504716, year = {2024}, author = {Niebauer, JH and Iscel, A and Schedl, S and Capelle, C and Kahr, M and Schamilow, S and Faltas, J and Srdits, M and Badr-Eslam, R and Lichtenauer, M and Zoufaly, A and Valenta, R and Hoffmann, S and Charwat-Resl, S and Krestan, C and Hitzl, W and Wenisch, C and Bonderman, D}, title = {Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1366269}, pmid = {38504716}, issn = {2297-055X}, abstract = {INTRODUCTION: SARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection.

METHODS: This prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a laboratory panel. At the time of the second follow-up visit at 18 months, patients without pathologic findings during the first study visit were contacted by phone to inquire about the course of their symptoms. In all other patients all initial examinations were repeated.

RESULTS: Two hundred Patients, who were hospitalized for COVID-19, were contacted by phone and were recruited for the study. Due to dropouts the second study visit was performed in 170 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long COVID with fatigue being the most common symptom (49%). Echocardiography at 6 months post discharge showed an impaired left ventricular function in 8% of which 80% returned to normal. Six months post discharge, cMRI revealed pericardial effusion in 17% which resolved in 47% of the 15 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients and were resolved in all 4 patients who attended control studies. At 6 months, chest CT scans identified post-infectious residues in 24%. In the 25 repeated chest CT scans 20% showed full recovery. Length of in-hospital stay was identified as a significant predictor for persisting Long COVID (95% CI: 1.005-1.12, p = 0.03).

CONCLUSION: Comparing 6 to 18 months, the prevalence of Long COVID decreased over time, but a high symptom burden remained. Structural and functional abnormalities were less frequent than the portrayed symptoms, and it thus remains a challenge to substantiate the symptoms.}, } @article {pmid38504691, year = {2024}, author = {Rahimi, F and Saadat, M and Hessam, M and Ravanbakhsh, M and Monjezi, S}, title = {Post-COVID-19 physical and cognitive impairments and associations with quality of life: a cross-sectional study.}, journal = {Frontiers in sports and active living}, volume = {6}, number = {}, pages = {1246585}, pmid = {38504691}, issn = {2624-9367}, abstract = {BACKGROUND AND OBJECTIVE: This study aimed to compare physical and cognitive functions between post-coronavirus disease 2019 (COVID-19) participants and healthy matched controls and investigate associations between physical and cognitive impairments with quality of life.

METHODS: Twenty-three post-COVID-19 participants and 23 age and sex-matched healthy people without a history of COVID-19 were included. Physical function was assessed using the Medical Research Council Sum Score (MRC-SS), 2 min Step Test, Modified Borg Scale, and Short Physical Performance Battery (SPPB) Test. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), and Stroop test, and the quality of life was evaluated using the Euro Quality of Life-5 Dimensions-3 Levels (EQ-5D-3l) questionnaire. Assessments were performed by a physical therapist in one session.

RESULTS: Mann-Whitney U test showed that in the post-COVID-19 group, compared to the control group, the number of steps in the 2 min Step Test (p < 0.001, ES = 0.57) and the scores of the SPPB (p = 0.03, ES = 0.32), MoCA (p = 0.003, ES = 0.44), Stroop test (p < 0.001, ES = 0.75), and the EQ-5D-3l visual analog scale (p = 0.027, ES = 0.32) were significantly lower. In addition, the Modified Borg Scale score (p < 0.001, ES = 0.6), TMT-A (p = 0.013, ES = 0.36) and TMT-B (p = 0.016, ES = 0.35) times, and the Stroop time (p < 0.001, ES = 0.61) were significantly higher in the post-COVID-19 group. There were no significant between-group differences in the MRC-SS score (p = 0.055, ES = 0.28). Furthermore, there were significant moderate to high associations between physical and cognitive functions and the quality of life in post-COVID-19 participants.

CONCLUSIONS: On average 4 months after symptomatic COVID-19, post-COVID-19 participants had significant impairments in physical and cognitive functions compared to healthy matched controls that were significantly correlated with the quality of life. These findings highlight the need for a comprehensive assessment to plan appropriate management strategies.}, } @article {pmid38504676, year = {2024}, author = {Wang, Z and Bao, S}, title = {The impact of social distancing measures (quarantine) policy on tertiary education and medical consultations in China during the COVID-19 pandemic.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1365805}, pmid = {38504676}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Quarantine ; Physical Distancing ; Pandemics ; Policy ; Referral and Consultation ; }, } @article {pmid38504586, year = {2024}, author = {Brogna, C and Montano, L and Zanolin, ME and Bisaccia, DR and Ciammetti, G and Viduto, V and Fabrowski, M and Baig, AM and Gerlach, J and Gennaro, I and Bignardi, E and Brogna, B and Frongillo, A and Cristoni, S and Piscopo, M}, title = {A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29507}, doi = {10.1002/jmv.29507}, pmid = {38504586}, issn = {1096-9071}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *COVID-19/prevention & control ; Rifaximin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Retrospective Studies ; Anti-Inflammatory Agents, Non-Steroidal ; Adrenal Cortex Hormones ; }, abstract = {The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.}, } @article {pmid38503738, year = {2024}, author = {Li, Y and Qin, S and Dong, L and Qiao, S and Wang, X and Yu, D and Gao, P and Hou, Y and Quan, S and Li, Y and Fan, F and Zhao, X and Ma, Y and Gao, GF}, title = {Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2444}, pmid = {38503738}, issn = {2041-1723}, support = {2023M743729//China Postdoctoral Science Foundation/ ; 2022M723344//China Postdoctoral Science Foundation/ ; 82222040//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170004//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2020092//Youth Innovation Promotion Association of the Chinese Academy of Sciences (Youth Innovation Promotion Association CAS)/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Prospective Studies ; *Breakthrough Infections ; Proteomics ; Retrospective Studies ; Antibodies, Neutralizing ; Antibodies, Viral ; }, abstract = {There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.}, } @article {pmid38503498, year = {2024}, author = {Gu, X and Huang, L and Li, X and Zhou, Y and Zhang, H and Wang, Y and Cui, D and Yu, T and Wang, Y and Cao, B}, title = {Association of Monocyte Count With Lung Function and Exercise Capacity Among Hospitalized COVID-19 Survivors: A 2-Year Cohort Study.}, journal = {Influenza and other respiratory viruses}, volume = {18}, number = {3}, pages = {e13263}, pmid = {38503498}, issn = {1750-2659}, support = {82041011//National Natural Science Foundation of China/ ; 82200114//National Natural Science Foundation of China/ ; 2018-I2M-1-003//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2020-I2M-CoV19-005//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 2018YFC1200102//National Key Research and Development Program of China/ ; ZYYCXTD-D-202208//National Administration of Traditional Chinese Medicine/ ; 2020ZX09201001//Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis/ ; //China Evergrande Group/ ; //Jack Ma Foundation/ ; //Sino Biopharmaceutical/ ; //Ping An Insurance (Group)/ ; //New Sunshine Charity Foundation/ ; }, mesh = {Humans ; *COVID-19 ; Cohort Studies ; Monocytes ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Exercise Tolerance ; Lung ; Survivors ; *Olfaction Disorders ; }, abstract = {BACKGROUND: Abnormal changes of monocytes have been observed in acute COVID-19, whereas associations of monocyte count with long COVID were not sufficiently elucidated.

METHODS: A cohort study was conducted among COVID-19 survivors discharged from hospital. The primary outcomes were core symptoms of long COVID, distance walked in 6 min, and lung function, and the secondary outcomes were health-related quality of life and healthcare use after discharge. Latent variable mixture modeling was used to classify individuals into groups with similar trajectory of monocyte count from discharge to 2-year after symptom onset. Multivariable adjusted generalized linear regression models and logistic regression models were used to estimate the associations of monocyte count trajectories and monocyte count at discharge with outcomes.

RESULTS: In total, 1389 study participants were included in this study. Two monocyte count trajectories including high to normal high and normal trajectory were identified. After multivariable adjustment, participants in high to normal high trajectory group had an odds ratio (OR) of 2.52 (95% CI, 1.44-4.42) for smell disorder, 2.27 (1.27-4.04) for 6-min walking distance less than lower limit of normal range, 2.45 (1.08-5.57) for total lung capacity (TLC) < 80% of predicted, 3.37 (1.16-9.76) for personal care problem, and 1.70 (1.12-2.58) for rehospitalization after discharge at 2-year follow-up compared with those in normal trajectory group. Monocyte count at discharge showed similar results, which was associated with smell disorder, TLC < 80% of predicted, diffusion impairment, and rehospitalization.

CONCLUSIONS: Monocyte count may serve as an easily accessible marker for long-term management of people recovering from COVID-19.}, } @article {pmid38500907, year = {2024}, author = {Darraz, S and Omar, M and Lachkar, A and Abdeljaouad, N and Yacoubi, H}, title = {Aseptic Osteonecrosis of the Femoral Head: The Effect of Corticosteroid Therapy and Long COVID Syndrome.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54327}, pmid = {38500907}, issn = {2168-8184}, abstract = {SARS‑CoV‑2 infection remains a hot topic; it is characterized by its multi-systemic involvement. Corticosteroid intake has been the subject of worldwide attention as a potentially effective treatment against coronavirus disease 2019 (COVID-19). Corticosteroids are registered on the WHO list of essential medicines, easily accessible for a low price, and particularly useful for different categories of people. The authors highlight the impact of corticosteroid administration for COVID-19 treatment on the occurrence of aseptic osteonecrosis in the femoral head. They also examine the pace of onset in comparison to corticosteroid usage unrelated to COVID-19. This article presents a patient with osteonecrosis of the femoral head after taking corticosteroid therapy in the treatment of COVID-19. The dose taken by the patient is 90 mg of dexamethasone equivalent to 600 mg of prednisone. The patient experienced the onset of OTA, and the duration of development was three months, indicating a relatively brief period. Comparison was made with data from the literature from 6 months to 1 year after taking corticosteroids in a context outside of COVID-19.}, } @article {pmid38500880, year = {2024}, author = {Gheorghita, R and Soldanescu, I and Lobiuc, A and Caliman Sturdza, OA and Filip, R and Constantinescu-Bercu, A and Dimian, M and Mangul, S and Covasa, M}, title = {The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1344086}, pmid = {38500880}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Disease Management ; Disease Progression ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID's effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.}, } @article {pmid38499676, year = {2024}, author = {Kim, SE}, title = {Four years on: the career costs for scientists battling long COVID.}, journal = {Nature}, volume = {627}, number = {8004}, pages = {689-691}, doi = {10.1038/d41586-024-00819-w}, pmid = {38499676}, issn = {1476-4687}, mesh = {Female ; Humans ; *Employment ; Patients/psychology ; *Post-Acute COVID-19 Syndrome/psychology/rehabilitation ; *Research Personnel/psychology ; *Social Support ; Time Factors ; Male ; }, } @article {pmid38499289, year = {2024}, author = {McKeever, V}, title = {Long covid and myalgic encephalomyelitis/chronic fatigue syndrome are overlapping conditions.}, journal = {BMJ (Clinical research ed.)}, volume = {384}, number = {}, pages = {q613}, doi = {10.1136/bmj.q613}, pmid = {38499289}, issn = {1756-1833}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38499177, year = {2024}, author = {Epstein, NK and Yelin, D and Shitenberg, D and Yahav, D and Leibovici, L and Daitch, V and Margalit, I}, title = {One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study.}, journal = {Infectious diseases now}, volume = {54}, number = {3}, pages = {104890}, doi = {10.1016/j.idnow.2024.104890}, pmid = {38499177}, issn = {2666-9919}, mesh = {Humans ; Follow-Up Studies ; Prospective Studies ; Forced Expiratory Volume ; *Pulmonary Diffusing Capacity ; *COVID-19/epidemiology ; }, abstract = {Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.}, } @article {pmid38496502, year = {2024}, author = {Silva, J and Takahashi, T and Wood, J and Lu, P and Tabachnikova, A and Gehlhausen, JR and Greene, K and Bhattacharjee, B and Monteiro, VS and Lucas, C and Dhodapkar, RM and Tabacof, L and Peña-Hernandez, M and Kamath, K and Mao, T and Mccarthy, D and Medzhitov, R and van Dijk, D and Krumholz, HM and Guan, L and Putrino, D and Iwasaki, A}, title = {Sex differences in symptomatology and immune profiles of Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.29.24303568}, pmid = {38496502}, abstract = {Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection [1-7] . However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals [8] with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-β-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.}, } @article {pmid38495940, year = {2024}, author = {Mostafa, RH and Moustafa, A}, title = {Beyond acute infection: molecular mechanisms underpinning cardiovascular complications in long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1268571}, pmid = {38495940}, issn = {2297-055X}, abstract = {SARS-CoV-2, responsible for the global COVID-19 pandemic, has manifested significant cardiovascular implications for the infected population. These cardiovascular repercussions not only linger beyond the initial phase of illness but have also been observed in individuals who remain asymptomatic. This extended and pervasive impact is often called the post-acute COVID-19 syndrome (PACS) or "Long COVID". With the number of confirmed global cases approaching an alarming 756 million, the multifaceted challenges of Long COVID are undeniable. These challenges span from individual health complications to considerable burdens on worldwide healthcare systems. Our review comprehensively examines the complications of the persistent cardiovascular complications associated with COVID-19. Furthermore, we shed light on emerging therapeutic strategies that promise to manage and possibly mitigate these complications. We also introduce and discuss the profound concerns regarding the potential transgenerational repercussions of SARS-CoV-2, emphasizing the need for a proactive and informed approach to future research and clinical practice.}, } @article {pmid38495828, year = {2024}, author = {Gehanno, JF and Thaon, I and Pelissier, C and Rollin, L}, title = {Assessment of search strategies in Medline to identify studies on the impact of long COVID on workability.}, journal = {Frontiers in research metrics and analytics}, volume = {9}, number = {}, pages = {1300533}, pmid = {38495828}, issn = {2504-0537}, abstract = {OBJECTIVES: Studies on the impact of long COVID on work capacity are increasing but are difficult to locate in bibliographic databases, due to the heterogeneity of the terms used to describe this new condition and its consequences. This study aims to report on the effectiveness of different search strategies to find studies on the impact of long COVID on work participation in PubMed and to create validated search strings.

METHODS: We searched PubMed for articles published on Long COVID and including information about work. Relevant articles were identified and their reference lists were screened. Occupational health journals were manually scanned to identify articles that could have been missed. A total of 885 articles potentially relevant were collected and 120 were finally included in a gold standard database. Recall, Precision, and Number Needed to Read (NNR) of various keywords or combinations of keywords were assessed.

RESULTS: Overall, 123 search-words alone or in combination were tested. The highest Recalls with a single MeSH term or textword were 23 and 90%, respectively. Two different search strings were developed, one optimizing Recall while keeping Precision acceptable (Recall 98.3%, Precision 15.9%, NNR 6.3) and one optimizing Precision while keeping Recall acceptable (Recall 90.8%, Precision 26.1%, NNR 3.8).

CONCLUSIONS: No single MeSH term allows to find all relevant studies on the impact of long COVID on work ability in PubMed. The use of various MeSH and non-MeSH terms in combination is required to recover such studies without being overwhelmed by irrelevant articles.}, } @article {pmid38495273, year = {2024}, author = {Mak, LY and Chung, MSH and Li, X and Lai, FTT and Wan, EYF and Chui, CSL and Cheng, FWT and Chan, EWY and Cheung, CL and Au, ICH and Xiong, X and Seto, WK and Yuen, MF and Wong, CKH and Wong, ICK}, title = {Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease.}, journal = {World journal of hepatology}, volume = {16}, number = {2}, pages = {211-228}, pmid = {38495273}, issn = {1948-5182}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Chronic liver disease (CLD) was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

AIM: To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma (HCC) among patients with CLD.

METHODS: A retrospective, territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong. Patients with confirmed SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)+CLD] between January 1, 2020 and October 25, 2022 were identified and matched 1:1 by propensity-score with those without (COVID-19-CLD). Each patient was followed up until death, outcome event, or November 15, 2022. Primary outcome was incidence of HCC. Secondary outcomes included all-cause mortality, adverse hepatic outcomes, and different treatment strategies to HCC (curative, non-curative treatment, and palliative care). Analyses were further stratified by acute (within 20 d) and post-acute (21 d or beyond) phases of SARS-CoV-2 infection. Incidence rate ratios (IRRs) were estimated by Poisson regression models.

RESULTS: Of 193589 CLD patients (> 95% non-cirrhotic) in the cohort, 55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching. Upon 249-d median follow-up, COVID-19+CLD was not associated with increased risk of incident HCC (IRR: 1.19, 95%CI: 0.99-1.42, P = 0.06), but higher risks of receiving palliative care for HCC (IRR: 1.60, 95%CI: 1.46-1.75, P < 0.001), compared to COVID-19-CLD. In both acute and post-acute phases of infection, COVID-19+CLD were associated with increased risks of all-cause mortality (acute: IRR: 7.06, 95%CI: 5.78-8.63, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.14-1.36, P < 0.001) and adverse hepatic outcomes (acute: IRR: 1.98, 95%CI: 1.79-2.18, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.13-1.35, P < 0.001), compared to COVID-19-CLD.

CONCLUSION: Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC, they were more likely to receive palliative treatment than those without. The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.}, } @article {pmid38495122, year = {2024}, author = {Qiu, Y and Mo, C and Chen, L and Ye, W and Chen, G and Zhu, T}, title = {Alterations in microbiota of patients with COVID-19: implications for therapeutic interventions.}, journal = {MedComm}, volume = {5}, number = {4}, pages = {e513}, pmid = {38495122}, issn = {2688-2663}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently caused a global pandemic, resulting in more than 702 million people being infected and over 6.9 million deaths. Patients with coronavirus disease (COVID-19) may suffer from diarrhea, sleep disorders, depression, and even cognitive impairment, which is associated with long COVID during recovery. However, there remains no consensus on effective treatment methods. Studies have found that patients with COVID-19 have alterations in microbiota and their metabolites, particularly in the gut, which may be involved in the regulation of immune responses. Consumption of probiotics may alleviate the discomfort caused by inflammation and oxidative stress. However, the pathophysiological process underlying the alleviation of COVID-19-related symptoms and complications by targeting the microbiota remains unclear. In the current study, we summarize the latest research and evidence on the COVID-19 pandemic, together with symptoms of SARS-CoV-2 and vaccine use, with a focus on the relationship between microbiota alterations and COVID-19-related symptoms and vaccine use. This work provides evidence that probiotic-based interventions may improve COVID-19 symptoms by regulating gut microbiota and systemic immunity. Probiotics may also be used as adjuvants to improve vaccine efficacy.}, } @article {pmid38493682, year = {2024}, author = {Wild, C and MacLean, A and Nettleton, S and Hunt, K and Ziebland, S}, title = {The double invisibility of Long Covid in children.}, journal = {Social science & medicine (1982)}, volume = {347}, number = {}, pages = {116770}, doi = {10.1016/j.socscimed.2024.116770}, pmid = {38493682}, issn = {1873-5347}, mesh = {Child ; Adolescent ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Parents ; Caregivers ; }, abstract = {The Covid-19 pandemic has been dominated by discussions of mild and short-lasting cases or acutely serious or lethal forms of the disease; less attention has been paid to long-term Covid-19 symptoms ('Long Covid'), particularly in children. This analysis of the experiences of children and adolescents with Long Covid, and those of their parents/caregivers, argues that children with Long Covid encounter a 'double invisibility' due to the condition's limited social currency and their status as the youngest members of society. We draw on 39 narrative interviews about children's and adolescents' experiences, conducted in 2021-2022 in the United Kingdom. The occurrence of Long Covid in children challenges key aspects of a dominant pandemic narrative, some of which have persisted from the early stages of the pandemic into 2023. Analysis of our qualitative interviews demonstrates that participant experiences were shaped and undermined by the convergence of three elements of the dominant pandemic narrative: that Covid-19 is mild, and everyone recovers; that children are not badly affected by Covid-19; and that worst of the pandemic was essentially 'over' as early as 2021/2022. In the face of these characterisations of Covid-19 experience, young people and their families reported significant additional challenges in making the illness experiences of children and adolescents visible, and thus in gaining appropriate support from medical and educational professionals. We interpret this in relation to 'social currency' - the extent to which an illness elicits understanding and acceptance by wider society. Children and adolescents with Long Covid struggled to signal the severity of their condition and elicit care in the manner expected for other debilitating illnesses. This was exacerbated by assumptions and stereotypes about unwell children and adolescents, and their parents, and questioning of their candidacy as reliable, trustworthy patients.}, } @article {pmid38492271, year = {2024}, author = {Babiloni, C and Gentilini Cacciola, E and Tucci, F and Vassalini, P and Chilovi, A and Jakhar, D and Musat, AM and Salvatore, M and Soricelli, A and Stocchi, F and Vacca, L and Ferri, R and Catania, V and Mastroianni, C and D'Ettorre, G and Noce, G}, title = {Resting-state EEG rhythms are abnormal in post COVID-19 patients with brain fog without cognitive and affective disorders.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {161}, number = {}, pages = {159-172}, doi = {10.1016/j.clinph.2024.02.034}, pmid = {38492271}, issn = {1872-8952}, mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; Female ; Middle Aged ; *Electroencephalography/methods ; Adult ; Brain Waves/physiology ; Fatigue/physiopathology/etiology ; Aged ; Rest/physiology ; Brain/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent.

METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed.

RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms.

CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue.

SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.}, } @article {pmid38492007, year = {2024}, author = {Cantone, E and D'Ascanio, L and De Luca, P and Roccamatisi, D and La La Mantia, I and Brenner, MJ and Di Stadio, A}, title = {Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {281}, number = {7}, pages = {3671-3678}, pmid = {38492007}, issn = {1434-4726}, mesh = {Humans ; Female ; *COVID-19/complications ; Male ; Middle Aged ; *Olfaction Disorders/etiology/therapy/rehabilitation ; *Thioctic Acid/therapeutic use/administration & dosage ; Ethanolamines/therapeutic use ; Palmitic Acids/therapeutic use/administration & dosage ; Amides/therapeutic use ; Adult ; SARS-CoV-2 ; Treatment Outcome ; Aged ; Anosmia/etiology/therapy ; Smell/physiology ; Combined Modality Therapy ; Olfactory Training ; }, abstract = {PURPOSE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.

METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.

RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.

CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.}, } @article {pmid38491011, year = {2024}, author = {Aldridge, SJ and Agrawal, U and Murphy, S and Millington, T and Akbari, A and Almaghrabi, F and Anand, SN and Bedston, S and Goudie, R and Griffiths, R and Joy, M and Lowthian, E and de Lusignan, S and Patterson, L and Robertson, C and Rudan, I and Bradley, DT and Lyons, RA and Sheikh, A and Owen, RK}, title = {Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2363}, pmid = {38491011}, issn = {2041-1723}, support = {MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; SBF006\1122/DUK_/Diabetes UK/United Kingdom ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology/prevention & control ; *COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Vaccination ; Child, Preschool ; }, abstract = {SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).}, } @article {pmid38490304, year = {2024}, author = {Wu, Y and Sawano, M and Wu, Y and Shah, RM and Bishop, P and Iwasaki, A and Krumholz, HM}, title = {Factors Associated With Long COVID: Insights From Two Nationwide Surveys.}, journal = {The American journal of medicine}, volume = {137}, number = {6}, pages = {515-519}, doi = {10.1016/j.amjmed.2024.02.032}, pmid = {38490304}, issn = {1555-7162}, support = {U01 HL160279/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; Cross-Sectional Studies ; Adult ; *COVID-19/epidemiology ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome ; Aged ; Adolescent ; Young Adult ; Risk Factors ; Behavioral Risk Factor Surveillance System ; SARS-CoV-2 ; Sex Factors ; Age Factors ; Health Surveys ; }, abstract = {BACKGROUND: Long COVID is a multisystemic condition that affects the lives of millions of people globally, yet factors associated with it are poorly defined. Our purpose in this study was to identify factors associated with long COVID.

METHODS: This cross-sectional study used data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) and the 2022 National Health Interview Survey (NHIS). We restricted the sample to individuals aged 18 and older who reported a positive COVID-19 test or doctor's diagnosis. Individuals who reported symptoms of at least 3 months were assumed to have long COVID. We identified demographic and clinical characteristics associated with long COVID, in unadjusted and adjusted analyses.

RESULTS: The study included 124,313 individuals in the BRFSS cohort and 10,131 in the NHIS cohort who reported a COVID-19 infection, with 26,783 (21.5%) and 1797 (17.7%) reporting long COVID, respectively. We found middle age, female sex, lack of a college degree, and severity of acute COVID-19 infection to be associated with long COVID. In contrast, non-Hispanic Asian and Black Americans were less likely to report long COVID compared with non-Hispanic White individuals. These findings were consistent across datasets.

CONCLUSIONS: Several demographic features were associated with long COVID, which may be the result of social, clinical, or biological influences.}, } @article {pmid38486840, year = {2024}, author = {Wheibe, E and Dalkin, BH and Meltzer, HC and Russ-Sellers, R and Grier, JT}, title = {The Multisystem effects of Long COVID Syndrome and Potential Benefits of Massage Therapy in Long COVID Care.}, journal = {International journal of therapeutic massage & bodywork}, volume = {17}, number = {1}, pages = {19-42}, pmid = {38486840}, issn = {1916-257X}, abstract = {BACKGROUND: A major complication of infection with Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is the potential for Long COVID Syndrome. While the pathophysiology of Long COVID Syndrome has yet to be described, the disease presentation is characterized by long-term symptoms with debilitating effects on human health. A better understanding of Long COVID symptomology may open up new avenues for patient treatment such as massage therapy.

METHODS: From the PubMed database, cohort studies that examined post-infection COVID sequelae published between January 1st, 2021 and April 30th, 2021 were selected to investigate patient demographics and symptoms. A review of massage therapy literature since 2000 in conjunction with identified Long COVID symptoms was performed.

RESULTS: This systematic review identified 17 cohort studies across the world that investigated the symptomatology of patients suffering from post-COVID sequelae in multiple organ systems. We identified the pulmonary and nervous systems to be the organ systems most affected with post-COVID sequelae, with PTSD, fatigue, dyspnea, cough, sleep disturbances, loss of smell, abdominal pain, and decreased appetite as the most common symptoms reported by >20% of Long COVID patients. Massage therapy was historically found to provide benefits to patients experiencing similar symptoms to those identified in Long COVID.

CONCLUSIONS: Recognizing the need for new approaches to treatment for Long COVID Syndrome, we identify massage therapy as a potential therapeutic treatment to positively impact the organ systems affected by Long COVID, especially the high-incident symptoms, and improve patient quality of life.}, } @article {pmid38485476, year = {2024}, author = {Kitsios, GD and Blacka, S and Jacobs, JJ and Mirza, T and Naqvi, A and Gentry, H and Murray, C and Wang, X and Golubykh, K and Qurashi, H and Dodia, A and Risbano, M and Benigno, M and Emir, B and Weinstein, E and Bramson, C and Jiang, L and Dai, F and Szigethy, E and Mellors, JW and Methe, B and Sciurba, FC and Nouraie, SM and Morris, A}, title = {Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis.}, journal = {BMJ open}, volume = {14}, number = {3}, pages = {e077869}, pmid = {38485476}, issn = {2044-6055}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prospective Studies ; Self Report ; COVID-19 Testing ; Latent Class Analysis ; RNA, Viral ; SARS-CoV-2 ; Disease Progression ; Dyspnea ; }, abstract = {OBJECTIVE: To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).

DESIGN: Prospective, observational cohort study of subjects with PASC.

SETTING: Academic tertiary centre from five clinical referral sources.

PARTICIPANTS: Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19.

EXPOSURES: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR.

OUTCOMES MEASURES: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load.

RESULTS: We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6-11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1-6)) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically active PASC subphenotypes: a high burden constitutional symptoms (21.9%), a persistent loss/change of smell and taste (20.6%) and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001) as well as referral source for enrolment. Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes.

CONCLUSIONS: We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.}, } @article {pmid38485228, year = {2024}, author = {Robertson, L}, title = {Did 'long COVID' increase road deaths in the USA?.}, journal = {Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention}, volume = {}, number = {}, pages = {}, doi = {10.1136/ip-2023-045136}, pmid = {38485228}, issn = {1475-5785}, abstract = {OBJECTIVE: To examine data on COVID-19 disease associated with a 10% increase in US road deaths from 2020 to 2021 that raises the question of the potential effect of pandemic stress and neurological damage from COVID-19 disease.

METHODS: Poisson regression was used to estimate the association of recent COVID-19 cases, accumulated cases, maximum temperatures, truck registrations and gasoline prices with road deaths monthly among US states in 2021. Using the regression coefficients, changes in each risk factor from 2020 to 2021 were used to calculate expected deaths in 2021 if each factor had remained the same as in 2020.

RESULTS: Corrected for the other risk factors, road deaths were associated with accumulated COVID-19 cases but not concurrent cases. More than 20 700 road deaths were associated with the changes in accumulated COVID-19 cases but were substantially offset by about 19 100 less-than-expected deaths associated with increased gasoline prices.

CONCLUSIONS: The lingering effects of COVID-19 on neurological function may be a risk factor for behaviour leading to road deaths.}, } @article {pmid38484930, year = {2024}, author = {Hosozawa, M and Hori, M and Hayama-Terada, M and Arisa, I and Muto, Y and Kitamura, A and Takayama, Y and Iso, H}, title = {Prevalence and risk factors of post-coronavirus disease 2019 condition among children and adolescents in Japan: A matched case-control study in the general population.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {143}, number = {}, pages = {107008}, doi = {10.1016/j.ijid.2024.107008}, pmid = {38484930}, issn = {1878-3511}, mesh = {Humans ; Female ; Child ; Male ; *COVID-19/epidemiology ; Case-Control Studies ; Risk Factors ; Adolescent ; Japan/epidemiology ; Prevalence ; Child, Preschool ; *SARS-CoV-2 ; COVID-19 Vaccines/administration & dosage ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To examine prevalence and risk factors for post-COVID-19 condition (PCC) in a paediatric population.

METHODS: The study included patients aged 5-17 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 March 2021 and 30 April 2022 and matched non-infected controls from Yao City, Japan. We compared parent-reported symptoms persisting ≥2 months (present at 3 months post-infection for patients) between the groups. COVID-19 vaccination data was obtained from the Vaccination Registry.

RESULTS: Among 8167 invited individuals, 3141 (1800 cases, mean age: 10.4 years, 46.1% females; 1341 controls, mean age 10.5 years, 47.1% females) participated. Patients had elapsed average 273 (185-605) days from infection, and 1708 (94.9%) experienced mild acute symptoms. Patients had higher odds of having persistent symptoms than did controls (6.3% vs 2.2%, adjusted odds ratio [aOR]: 3.15, 95% confidence interval: 2.08-4.77), with 53.6% of them reporting current disruption due to the symptoms. Older age, low household income, pre-existing allergy, and autonomic nervous system disease were associated with increased risks of developing PCC; two prior vaccination doses reduced these risks (aOR: 0.53, 0.29-0.96).

CONCLUSION: SARS-CoV-2 infection, including omicron infections heighten persistent symptom risk in the paediatric population, necessitating preventive strategies, notably vaccination.}, } @article {pmid38484350, year = {2024}, author = {Erkan, M}, title = {Age and chest computed tomography severity score are predictors of long-COVID.}, journal = {Journal of infection in developing countries}, volume = {18}, number = {2}, pages = {195-200}, doi = {10.3855/jidc.18276}, pmid = {38484350}, issn = {1972-2680}, mesh = {Humans ; Adult ; Middle Aged ; *COVID-19/diagnostic imaging ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Tomography, X-Ray Computed ; Lung/diagnostic imaging ; }, abstract = {INTRODUCTION: About one-third of acute coronavirus disease 2019 (COVID-19) survivors have suffered from persisting symptoms called long-COVID. Clinical factors such as age and intensity (moderate or acute) of COVID-19 have been found to be associated with long-COVID. Many tissues might be damaged functionally or structurally during acute COVID-19 which can be detected by blood assays and chest computed tomography (CT). We aimed to evaluate the relationship between long-COVID and the initial findings of blood assays and chest CT as possible predictors.

METHODOLOGY: The study included patients with acute COVID-19. Laboratory tests and chest CT were obtained from each patient at the time of admission to the hospital. Chest CT was evaluated for pneumonic involvement and severity score. Multivariable regression model was created to find the factors that were independently associated with long-COVID.

RESULTS: There were 60 (38.2%) patients with long-COVID and 97 (61.8%) without. Baseline demographic, laboratory and chest CT parameters were similar in both groups, except for age, chronic lung disease and chest CT severity score (46.9 ± 15.1 years vs 52.6 ± 15.9 years, p = 0.03; 11.7% vs 3.1%, p = 0.03 and 10.3 ± 9.6 vs 6.5 ± 7.6, p = 0.02, respectively). In multivariable model, chest CT severity score (OR: 1.059, 95% CI: 1.002-1.119, p = 0.04) and age (OR: 0.953, 95% CI: 0.928-0.979, p < 0.001) were independently associated with long-COVID.

CONCLUSIONS: Chest CT severity score and age were independently associated with long-COVID and may be used to predict the future risk of long-COVID.}, } @article {pmid38483537, year = {2024}, author = {Chen, M and Pekosz, A and Villano, JS and Shen, W and Zhou, R and Kulaga, H and Li, Z and Smith, A and Gurung, A and Beck, SE and Witwer, KW and Mankowski, JL and Ramanathan, M and Rowan, NR and Lane, AP}, title = {Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {8}, pages = {}, pmid = {38483537}, issn = {1558-8238}, support = {R01 AI132590/AI/NIAID NIH HHS/United States ; R01 AI144997/AI/NIAID NIH HHS/United States ; R01 DC016106/DC/NIDCD NIH HHS/United States ; R01 DC020841/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Cricetinae ; Humans ; Aged ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Axons ; *Common Cold ; }, abstract = {SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.}, } @article {pmid38483046, year = {2024}, author = {Pietrangelo, T and Cagnin, S and Bondi, D and Santangelo, C and Marramiero, L and Purcaro, C and Bonadio, RS and Di Filippo, ES and Mancinelli, R and Fulle, S and Verratti, V and Cheng, X}, title = {Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances.}, journal = {Acta physiologica (Oxford, England)}, volume = {240}, number = {4}, pages = {e14122}, doi = {10.1111/apha.14122}, pmid = {38483046}, issn = {1748-1716}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Muscle, Skeletal/metabolism ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID-19 pandemic since ME/CFS and long-COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research. This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long-standing debate on terminology.}, } @article {pmid38482000, year = {2024}, author = {Bohmwald, K and Diethelm-Varela, B and Rodríguez-Guilarte, L and Rivera, T and Riedel, CA and González, PA and Kalergis, AM}, title = {Pathophysiological, immunological, and inflammatory features of long COVID.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1341600}, pmid = {38482000}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; Kinetics ; Persistent Infection ; }, abstract = {The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.}, } @article {pmid38481394, year = {2024}, author = {Oleribe, OO and Taylor-Robinson, AW and Nwanyanwu, OC and Morgan, MY and Taylor-Robinson, SD}, title = {Four Years Since COVID-19 Day Zero: A Time to Evaluate Past and Future Pandemic Control Policies and Practices in Sub-Saharan Africa?.}, journal = {Risk management and healthcare policy}, volume = {17}, number = {}, pages = {505-511}, pmid = {38481394}, issn = {1179-1594}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Four years after the first case of COVID-19, the world is still determining how best to prevent and control the long-term effects of SARS-CoV-2 infection. Non-pharmaceutical interventions (NPIs) were employed at the start of the pandemic as the only available options, prior to effective vaccines and antiviral agents. The World Health Organization recommended dual vaccination for 70% worldwide as the threshold for a return to "normal" community life. Immunization rates needed to increase in all global regions, irrespective of socioeconomic status, necessitating more equitable access. During the pandemic, wealthier countries hoarded vaccine supplies even when their citizens were immunized. This highlights the already enormous difficulties in healthcare provision faced by low-income sub-Saharan African countries, which remain at risk as industrialized nations have progressed to a post-pandemic era. Thus, in addition to redoubling vaccination efforts public health policymakers should consider ongoing and future use of NPIs. In this narrative account, we advocate that various NPI practices should not be shelved; rather, more research is needed to evaluate their impact in parallel with booster vaccination. This especially applies to so-called "long COVID". Lessons learned from implementing best practices in resource-limited settings should be incorporated into preparedness guidelines for future infectious disease outbreaks.}, } @article {pmid38481384, year = {2024}, author = {Turk, F and Sweetman, J and Chew-Graham, CA and Gabbay, M and Shepherd, J and van der Feltz-Cornelis, C and , }, title = {Accessing care for Long Covid from the perspectives of patients and healthcare practitioners: A qualitative study.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {2}, pages = {e14008}, pmid = {38481384}, issn = {1369-7625}, support = {COV-LT2-0043//NIHR/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/therapy ; Pandemics ; Health Services ; Health Services Accessibility ; Qualitative Research ; }, abstract = {BACKGROUND: Long Covid is an emerging long-term condition, with those affected raising concerns about lack of healthcare support.

OBJECTIVE: We conducted a qualitative study to identify facilitators and barriers to healthcare access for people with Long Covid, aiming to enhance our understanding of the specific nature of these barriers and how patient experiences may vary.

SETTING AND PARTICIPANTS: In the context of the Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways (STIMULATE-ICP) Delphi study, a nationally distributed online survey was conducted. Eight patients and eight healthcare practitioners (HCP) were interviewed via telephone or video call. Framework analysis, sensitised by the candidacy theory, was used to identify barriers and facilitators over four levels of access to care.

RESULTS: Three themes were identified: (i) patients' efforts to navigate emerging pathways for Long Covid, (ii) the patient-HCP interaction and (iii) service resources and structural constraints. Barriers to specialist care included long waiting times, communication gaps across services and a lack of continuity in care. Facilitators included collaborative, patient-centred approaches, patients' active role in their healthcare and blended approaches for appointments. The perspectives of both patients and HCPs largely aligned.

DISCUSSION: The candidacy framework was valuable in understanding the experiences of people with Long Covid seeking access to healthcare. Individuals perceived themselves as eligible for care, but they often encountered obstacles in obtaining the expected level of care or, in some cases, did not receive it at all. Our findings are discussed in the context of the candidacy model through multiple processes of identification, negotiation, permeability and appearances at health services. These themes seem to be especially important for the emerging new pathway model and are relevant to both primary and secondary care.

CONCLUSIONS: This study highlights that despite these interviews being conducted two years after the start of the COVID-19 pandemic, people with Long Covid still struggle to access healthcare, emphasising the ongoing need to provide equitable timely healthcare access for people with Long Covid.

People with Long Covid advised on all stages of this research.}, } @article {pmid38481230, year = {2024}, author = {Leggat, FJ and Heaton-Shrestha, C and Fish, J and Siriwardena, AN and Domeney, A and Rowe, C and Patel, I and Parsons, J and Blair, J and Jones, F}, title = {An exploration of the experiences and self-generated strategies used when navigating everyday life with Long Covid.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {789}, pmid = {38481230}, issn = {1471-2458}, support = {COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; COV-LT2- 0009//National Institute for Health and Care Research/ ; }, mesh = {Adult ; Humans ; Middle Aged ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Qualitative Research ; Palliative Care ; *Self-Management ; }, abstract = {BACKGROUND: Around one in ten people who contract Covid-19 report ongoing symptoms or 'Long Covid'. Without any known interventions to cure the condition, forms of self-management are routinely prescribed by healthcare professionals and described by people with the condition. However, there is limited research exploring what strategies are used to navigate everyday life with Long Covid, and experiences that initiate development of these strategies. Our study aimed to explore the range and influence of self-generated strategies used by people with Long Covid to navigate everyday life within the context of their own condition.

METHODS: Forming part of the Long Covid Personalised Self-managemenT support co-design and EvaluatioN (LISTEN) project, we conducted a qualitative study using narrative interviews with adults who were not hospitalised with Covid-19. Participants aged over 18 years, who self-identified with Long Covid, were recruited from England and Wales. Data were analysed with patient contributors using a reflexive thematic analysis.

RESULTS: Eighteen participants (mean age = 44 years, SD = 13 years) took part in interviews held between December 2021 and February 2022. Themes were constructed which depicted 1) the landscape behind the Long Covid experience and 2) the everyday experience of participants' Long Covid. The everyday experience comprised a combination of physical, emotional, and social factors, forming three sub-themes: centrality of physical symptoms, navigating 'experts' and the 'true colour' of personal communities, and a rollercoaster of psychological ambiguity). The third theme, personal strategies to manage everyday life was constructed from participants' unique presentations and self-generated solutions to manage everyday life. This comprised five sub-themes: seeking reassurance and knowledge, developing greater self-awareness through monitoring, trial and error of 'safe' ideas, building in pleasure and comfort, and prioritising 'me'.

CONCLUSIONS: Among this sample of adults with Long Covid, their experiences highlighted the unpredictable nature of the condition but also the use of creative and wide ranging self-generated strategies. The results offer people with Long Covid, and healthcare professionals supporting them, an overview of the collective evidence relating to individuals' self-management which can enable ways to live 'better' and regain some sense of identity whilst facing the impact of a debilitating, episodic condition.

TRIAL REGISTRATION: LISTEN ISRCTN36407216.}, } @article {pmid38481207, year = {2024}, author = {Duan, C and Liu, L and Wang, T and Wang, G and Jiang, Z and Li, H and Zhang, G and Ye, L and Li, C and Cao, Y}, title = {Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {116}, pmid = {38481207}, issn = {1741-7015}, support = {National Natural Science Foundation of China//National Natural Science Foundation of China/ ; 24NSFSC3535//Natural Science Foundation of Sichuan Province/ ; RD-02-202409//West China School of Stomatology, Sichuan University/ ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Systematic Reviews as Topic ; }, abstract = {BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus.

METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures.

RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression.

CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.}, } @article {pmid38481048, year = {2024}, author = {Vo, HT and Dao, TD and Duong, TV and Nguyen, TT and Do, BN and Do, TX and Pham, KM and Vu, VH and Pham, LV and Nguyen, LTH and Le, LTH and Nguyen, HC and Dang, NH and Nguyen, TH and Nguyen, AT and Nguyen, HV and Nguyen, PB and Nguyen, HTT and Pham, TTM and Le, TT and Nguyen, TTP and Tran, CQ and Nguyen, KT}, title = {Impact of long COVID-19 on posttraumatic stress disorder as modified by health literacy: an observational study in Vietnam.}, journal = {Osong public health and research perspectives}, volume = {15}, number = {1}, pages = {33-44}, pmid = {38481048}, issn = {2210-9099}, abstract = {BACKGROUND: The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a "social vaccine" that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association.

METHODS: A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions.

RESULTS: Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63-2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97-0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96-0.99; p=0.001).

CONCLUSION: Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.}, } @article {pmid38477520, year = {2024}, author = {Ryan-Claytor, C and Verdery, A}, title = {Research Note: A Novel Sullivan Method Projection Framework With Application to Long COVID.}, journal = {Demography}, volume = {61}, number = {2}, pages = {267-281}, doi = {10.1215/00703370-11226858}, pmid = {38477520}, issn = {1533-7790}, mesh = {Humans ; *Life Expectancy ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; }, abstract = {Originally developed for estimating healthy life expectancy, the traditional Sullivan method continues to be a popular tool for obtaining point-in-time estimates of the population impacts of a wide range of health and social conditions. However, except in rare data-intensive cases, the method is subject to stringent stationarity assumptions, which often do not align with real-world conditions and restrict its resulting estimates and applications. In this research note, we present an expansion of the original method to apply within a population projection framework. The Sullivan method projection framework produces estimates that offer new insights about future trends in population health and social arrangements under various demographic and epidemiologic scenarios, such as the percentage of life years that population members can expect to spend with a condition of interest in a time interval under different assumptions. We demonstrate the utility of this framework using the case of long COVID, illustrating both its operation and potential to reveal insights about emergent population health challenges under various theoretically informed scenarios. The traditional Sullivan method provides a summary measure of the present, while its incorporation into a projection framework enables preparation for a variety of potential futures.}, } @article {pmid38476627, year = {2024}, author = {Bota, AV and Bogdan, I and Razvan, DV and Ilie, AC and Tudor, R and Indries, MF and Csep, AN and Marincu, I}, title = {A Three-Year Cross-Sectional Analysis of Depression, Anxiety, and Quality of Life in Patients with Post-COVID-19 Syndrome.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {751-762}, pmid = {38476627}, issn = {1178-7074}, abstract = {BACKGROUND: This study explores the longitudinal psychosocial impact of Long-COVID syndrome, also known as Post-COVID-19 syndrome, characterized by enduring symptoms after coronavirus disease (COVID-19) infection, over the years 2020, 2021, and 2022. It aimed to examine the variations in depression, anxiety, and quality of life among Post-COVID-19 patients during these years, hypothesizing significant inter-year differences reflecting the pandemic's evolving influence.

METHODS: Conducted at Victor Babes Hospital for Infectious Diseases and Pulmonology, Romania, this cross-sectional research involved 324 patients diagnosed with mild to moderate COVID-19, assessed six months post-hospitalization. Standardized instruments, namely Short Form (SF-36) for quality of life, Generalised Anxiety Disorder Assessment (GAD-7) for anxiety, and Patient Health Questionnaire (PHQ-9) for depression, were utilized.

RESULTS: The study observed a consistent average patient age of around 55 years across the years. A notable increase in COVID-19 vaccination rates was recorded, rising from 20.9% in 2020 to over 70% in 2022 (p<0.001). Trends in key post-COVID symptoms like fatigue and cognitive issues varied over the years. Importantly, there was a consistent decrease in feelings of sadness or depression, with scores declining from 7.3 in 2020 to 4.8 in 2022 (p<0.001). The SF-36 survey indicated a steady improvement in overall health, reaching 55.8±7.1 in 2022 (p=0.035). Both GAD-7 and PHQ-9 scores showed significant reductions in anxiety and depression over the years, with p-values of 0.030 and 0.031, respectively. Factors such as smoking status, substance use, and the initial severity of COVID-19 infection were significantly associated with depression levels.

CONCLUSION: The findings suggest that despite persistent physical symptoms, Long-COVID patients experienced enhancements in mental well-being and quality of life over the studied period. The increasing vaccination rates might have contributed to this improvement. Addressing modifiable risk factors like smoking and substance use could further optimize post-COVID care and mental health outcomes.}, } @article {pmid38474072, year = {2024}, author = {Smith, MM and Melrose, J}, title = {Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474072}, issn = {1422-0067}, support = {n/a//Melrose Personal Research Fund, Sydney, Australia/ ; }, mesh = {Humans ; *Proteoglycans ; Lumican ; Post-Acute COVID-19 Syndrome ; Chondroitin Sulfate Proteoglycans/metabolism ; *COVID-19 ; Biomarkers ; }, abstract = {This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae.}, } @article {pmid38472519, year = {2024}, author = {Aubry, A and Corvilain, E and Ghelfenstein-Ferreira, T and Camelena, F and Meignin, V and Berçot, B and Le Goff, J and Salmona, M}, title = {Unmasking Bartonella henselae infection in the shadows of long COVID thanks to clinical metagenomics.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {5}, pages = {1025-1029}, pmid = {38472519}, issn = {1435-4373}, mesh = {Humans ; Female ; *Bartonella henselae/genetics/isolation & purification ; Adult ; *COVID-19/diagnosis/complications ; *Metagenomics/methods ; SARS-CoV-2/genetics ; Anti-Bacterial Agents/therapeutic use ; Clarithromycin/therapeutic use ; }, abstract = {The diagnosis of long COVID often relies on symptoms post-COVID-19, occasionally lacking biological evidence. This case study illustrates how investigating long COVID uncovered an underlying bartonellosis through clinical metagenomics. Following mild COVID-19, a 26-year-old woman experienced persistent symptoms during 5 months, including axillary adenopathy. Pathological examination, 16 S rRNA PCR, and clinical metagenomic analysis were done on an adenopathy biopsy. The latter revealed Bartonella henselae DNA and RNA. Treatment with clarithromycin improved symptoms. This case underscores the relevance of clinical metagenomics in diagnosing hidden infections. Post-COVID symptoms warrant thorough investigation, and bartonellosis should be considered in polyadenopathy cases, regardless of a recent history of cat or flea exposures.}, } @article {pmid38472045, year = {2024}, author = {Santoro, F and Núñez-Gil, IJ and Viana-Llamas, MC and Alfonso-Rodríguez, E and Uribarri, A and Becerra-Muñoz, VM and Guzman, GF and Di Nunno, N and Lopez-Pais, J and Cerrato, E and Sinagra, G and Mapelli, M and Inciardi, RM and Specchia, C and Oriecuia, C and Brunetti, ND}, title = {Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.}, journal = {European journal of internal medicine}, volume = {124}, number = {}, pages = {108-114}, doi = {10.1016/j.ejim.2024.03.002}, pmid = {38472045}, issn = {1879-0828}, mesh = {Humans ; *COVID-19/mortality/epidemiology ; Male ; Female ; Middle Aged ; Aged ; *Hospitalization/statistics & numerical data ; Risk Assessment/methods ; *Registries ; *Cardiovascular Diseases/mortality/epidemiology ; Prognosis ; Aged, 80 and over ; SARS-CoV-2 ; Risk Factors ; Cause of Death ; Italy/epidemiology ; Follow-Up Studies ; }, abstract = {BACKGROUND: Long-term consequences of COVID-19 are still partly known.

AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients.

METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model.

RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01).

CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict follow-up.}, } @article {pmid38471366, year = {2024}, author = {Rodríguez Onieva, A and Soto Castro, CA and García Morales, V and Aneri Vacas, M and Hidalgo Requena, A}, title = {Long COVID: Factors influencing persistent symptoms and the impact of gender.}, journal = {Semergen}, volume = {50}, number = {5}, pages = {102208}, doi = {10.1016/j.semerg.2024.102208}, pmid = {38471366}, issn = {1578-8865}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; Sex Factors ; Risk Factors ; Adult ; Prevalence ; *Primary Health Care/statistics & numerical data ; *Post-Acute COVID-19 Syndrome ; Aged ; Hospitalization/statistics & numerical data ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to characterize the prevalence as well as clinical and epidemiological features of persistent symptoms after acute COVID-19, focusing on gender-specific differences in a primary care setting.

METHODS: A total of 1542 individuals with confirmed SARS-CoV-2 infection were enrolled. The study population comprised 55.77% females (mean age: 45.04 years). Risk factors for persistent COVID-19 were analyzed, revealing disparities between men and women. Symptom clusters and their prevalence were assessed over time, along with functional status using the post-COVID-19 functional status scale.

RESULTS: The prevalence of persistent COVID-19 was 12.38%, with females exhibiting a 1.5 times higher risk. Females displayed a higher number of visits and persistent symptoms at 90 days, decreasing after one year. Symptom clusters varied between genders, with females experiencing more dermatological issues. Functional status analysis revealed that females had a better pre-infection status, similar status to males at 90 days, and improved status at 180-, 270-, and 365-days post-infection. Logistic regression analysis showed significant associations between persistence, gender, hospitalization, radiological abnormalities, age, and immunosuppression.

CONCLUSION: This study provides insights into the prevalence and clinical characteristics of persistent COVID-19 in a primary care population. Females exhibited a higher risk of persistent symptoms and displayed distinct patterns in symptom clusters and functional status compared to males. These findings contribute to a better understanding of the long-term effects of COVID-19 and highlight the importance of gender-specific considerations in post-acute care.}, } @article {pmid38470857, year = {2024}, author = {Stone, M and Spencer, BR and Warden, DE and Fink, RV and Saa, P and Leddy, J and Mulach-Vannoy, J and Townsend, R and Krysztof, D and Hughes, AN and Di Germanio, C and Kessler, DA and Kleinman, S and Busch, MP and Norris, PJ}, title = {Patient and Immunological Factors Associated With Delayed Clearance of Mucosal Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Symptom Persistence.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {2}, pages = {357-362}, pmid = {38470857}, issn = {1537-6613}, support = {75N92019D00033/HL/NHLBI NIH HHS/United States ; HHSN 75N92019D00032/HL/NHLBI NIH HHS/United States ; /NH/NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; *COVID-19/immunology/diagnosis ; Male ; Female ; *SARS-CoV-2/immunology ; Middle Aged ; *RNA, Viral/blood ; Adult ; *Antibodies, Viral/blood ; Aged ; Immunoglobulin G/blood ; Reinfection/immunology/virology ; }, abstract = {Serial blood and mucosal samples were characterized for 102 participants enrolled a median of 7.0 days after coronavirus disease 2019 diagnosis. Mucosal RNA was detectable for a median of 31.5 (95% confidence interval [CI], 20.5-63.5) days, with persistence ≥1 month associated with obesity (body mass index [BMI] ≥30 kg/m2; odds ratio [OR], 3.9 [95% CI, 1.2-13.8]) but not age, sex, or chronic conditions. Fifteen participants had likely reinfection; lower serum anti-spike IgG levels were associated with reinfection risk. Nearly half of participants (47%) reported symptoms lasting ≥2-3 months; persistence ≥3 months was associated with BMI ≥30 kg/m2 (OR, 4.2 [95% CI, 1.1-12.8]) and peak anti-spike and anti-nucleocapsid antibody levels.}, } @article {pmid38469363, year = {2024}, author = {Magaki, S and Zhang, T and Han, K and Hilda, M and Yong, WH and Achim, C and Fishbein, G and Fishbein, MC and Garner, O and Salamon, N and Williams, CK and Valdes-Sueiras, MA and Hsu, JJ and Kelesidis, T and Mathisen, GE and Lavretsky, H and Singer, EJ and Vinters, HV}, title = {HIV and COVID-19: two pandemics with significant (but different) central nervous system complications.}, journal = {Free neuropathology}, volume = {5}, number = {}, pages = {}, pmid = {38469363}, issn = {2699-4445}, support = {R01 AG059502/AG/NIA NIH HHS/United States ; U24 MH100929/MH/NIMH NIH HHS/United States ; }, abstract = {Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions.}, } @article {pmid38469293, year = {2024}, author = {Collins, CP and Longo, DL and Murphy, WJ}, title = {The immunobiology of SARS-CoV-2 infection and vaccine responses: potential influences of cross-reactive memory responses and aging on efficacy and off-target effects.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1345499}, pmid = {38469293}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Vaccines ; Aging ; Immunoglobulin Idiotypes ; }, abstract = {Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution of infection, called post-acute sequelae of COVID-19 (PASC) or "Long COVID," suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing and potentially cross-reactive immunity, which can then affect primary SARS-CoV-2 infection, as well as vaccination responses. The influence of pre-existing immunity from these hCoVs, as well as responses generated from original CoV2 strains or vaccines on the development of new high-affinity responses to CoV2 antigenic viral variants, needs to be better understood given the need for continuous vaccine adaptation and application in the population. Due in part to thymic involution, normal aging is associated with reduced naïve T cell compartments and impaired primary antigen responsiveness, resulting in a reliance on the pre-existing cross-reactive memory cell pool which may be of lower affinity, restricted in diversity, or of shorter duration. These effects can also be mediated by the presence of down-regulatory anti-idiotype responses which also increase in aging. Given the tremendous heterogeneity of clinical data, utilization of preclinical models offers the greatest ability to assess immune responses under a controlled setting. These models should now involve prior antigen/viral exposure combined with incorporation of modifying factors such as age on immune responses and effects. This will also allow for mechanistic dissection and understanding of the different immune pathways involved in both SARS-CoV-2 pathogen and potential vaccine responses over time and how pre-existing memory responses, including potential anti-idiotype responses, can affect efficacy as well as potential off-target effects in different tissues as well as modeling PASC.}, } @article {pmid38468999, year = {2024}, author = {Butt, MA and Abdullah, MA and Waseem, M and Ahmed, H and Aamir, A and Asif, R and Durrani, HM}, title = {Prevalence of Long COVID Syndrome and its Association With Blood Group: A Cross-Sectional Study.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e53966}, pmid = {38468999}, issn = {2168-8184}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) virus pandemic rapidly spread across the globe since 2020. It was characterized by a number of acute signs and symptoms. There were, however, some new-onset signs and symptoms labelled as "Long COVID". This study was conducted to study its prevalence and associations with blood group.

METHODS: A retrospective analysis was conducted in Islamabad for patients diagnosed with COVID-19 in 2020-2021. Information was collected through an online and physical questionnaire regarding personal demographics, symptoms during and after COVID-19, and blood group. The data was analyzed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, New York, United States).

RESULTS: The study identified 196 participants out of which 48.5% were male and 51% were female, with a median age of 30. Most participants (62.2%) belonged to the Punjabi ethnicity. The mean BMI was 25.56 kg/m[2]. The majority of the study participants reported having blood group B (n=76) followed by A (n=52). Acute symptoms were experienced by 95.4% of participants, with fatigue being the most persistent symptom at four weeks (45.9%). After four weeks, 63.3% of participants reported new symptoms like hair loss. Females were found more likely to experience long COVID symptoms. The perceived severity of acute infection was significantly associated with long COVID symptoms (p=<0.01). There was no association found between long COVID and blood group (p=0.158).

CONCLUSION:  There was no association found between long COVID and ABO blood groups. Females were more likely than males to experience long COVID. Long COVID was found to be more likely to develop in those with perceived severe acute infection, highlighting the need for further research regarding aggressive care from the onset of COVID-19 infection.}, } @article {pmid38468535, year = {2024}, author = {Balzanelli, MG and Rastmanesh, R and Distratis, P and Lazzaro, R and Inchingolo, F and Del Prete, R and Pham, VH and Aityan, SK and Cong, TT and Nguyen, KCD and Isacco, CG}, title = {The Role of SARS-CoV-2 Spike Protein in Long-term Damage of Tissues and Organs, the Underestimated Role of Retrotransposons and Stem Cells, a Working Hypothesis.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303283480240227113401}, pmid = {38468535}, issn = {2212-3873}, abstract = {Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume-Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine.}, } @article {pmid38468492, year = {2024}, author = {Liu, S and Devason, AS and Levy, M}, title = {From intestinal metabolites to the brain: Investigating the mysteries of Long COVID.}, journal = {Clinical and translational medicine}, volume = {14}, number = {3}, pages = {e1608}, pmid = {38468492}, issn = {2001-1326}, support = {P30 ES013508/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Brain ; }, } @article {pmid38468304, year = {2024}, author = {Brandt, F and Simone, G and Loth, J and Schilling, D}, title = {COVID-19-associated costs and mortality in Germany: an incidence-based analysis from a payer's perspective.}, journal = {BMC health services research}, volume = {24}, number = {1}, pages = {321}, pmid = {38468304}, issn = {1472-6963}, mesh = {Humans ; Aged ; Retrospective Studies ; Incidence ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Health Care Costs ; Germany/epidemiology ; }, abstract = {BACKGROUND: This study aims to estimate average COVID-19-associated healthcare costs per capita in Germany from a payer perspective. In addition, insights into COVID-19-associated mortality should be gained.

METHODS: For this purpose, a retrospective longitudinal analysis using health insurance claims data was performed. Patients affected by COVID-19 in Q1/2021 (investigation group (IG)) were compared to a matched non-COVID-19 control group (CG) (1:1 propensity score matching (PSM)). Mean values of healthcare costs in 2020 and 2021 were computed for both groups and then separated by age and by development of Post-COVID-19 Syndrome (PCS). Group differences were examined using Mann-Whitney U test (α = 0.05). Difference-in-Differences approach (DiD) was used to estimate average cost effects of COVID-19 in 2021. Concerning mortality, the number of deaths in 2021 was compared between IG and CG using χ[2] test of independence.

RESULTS: A total of 8,014 insurants were included (n = 4,007 per group; n = 536 per group examining PCS patients only). Total healthcare costs varied a lot in the sample, were comparable between IG and CG in 2020, but were significantly higher in the IG in 2021 (DiD estimate = € 1,063 (in total); € 3,242 (PCS group)). This was more pronounced in the older age groups. High hospital costs of a minority of patients were the most influential driver of COVID-19-associated healthcare costs. Mortality was more than doubled in the IG (tripled in patients aged ≥ 60).

CONCLUSIONS: COVID-19 is associated with significantly increased healthcare costs and mortality, especially in older age groups. The additional development of PCS further increases the costs of COVID-19.}, } @article {pmid38467123, year = {2024}, author = {Lippi, G and Mattiuzzi, C and Sanchis-Gomar, F}, title = {Physical Activity, Long-COVID, and Inactivity: A Detrimental Endless Loop.}, journal = {Journal of physical activity & health}, volume = {21}, number = {5}, pages = {420-422}, doi = {10.1123/jpah.2024-0057}, pmid = {38467123}, issn = {1543-5474}, mesh = {Humans ; *Exercise ; *COVID-19/epidemiology ; *Sedentary Behavior ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, abstract = {The risk of developing medium- and long-term sequelae after recovery from COVID-19 is validated. Long-COVID burden represents a major health care issue, thus paving the way to effective prevention and/or treatment measures. Physical activity prevents many human pathologies, including COVID-19. Being physically active before and immediately after a severe acute respiratory syndrome coronavirus 2 infection substantially lowers the risk of developing long-COVID. In addition, long-COVID is an important cause of physical inactivity. Physically inactive individuals are at increased risk of developing long-COVID, while patients with long-COVID are more likely to reduce their physical activity levels after recovering from the acute infection, with the risk of generating a continuous loop. This harmful interaction needs to be recognized by public health institutions, and the adoption of physical activity as a routine clinical practice in all individuals after a severe acute respiratory syndrome coronavirus 2 infection needs to be proactively promoted.}, } @article {pmid38466665, year = {2024}, author = {Shrestha, DS and Manandhar, S and Chalise, BS and Rajbhandari, SK and Bastola, A and Bhandari, P and Das, SK and Pant, P and Sharma, S and Kattel, HP and Jha, RK and Shrestha, MR and Shrestha, A and Love, RR}, title = {Symptoms 6 months following SARS-CoV-2 infection in Nepali women.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0299141}, pmid = {38466665}, issn = {1932-6203}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Retrospective Studies ; *Arthritis, Rheumatoid ; }, abstract = {In Nepal, over 1 million individuals have tested positive for SARS-CoV-2. We sought to describe the frequency of nonrecovery from this infection at 6 months and associated symptoms. We conducted a retrospective cohort study of 6142 women who had positive and negative PCR tests for this infection 6 months previously at 3 institutions in Kathmandu. In telephone interviews women provided information on 22 symptoms and their intensities, health status and history, and functional status. Of 3732 women who had tested PCR positive, 630 (16.9%) reported that they were unrecovered. These 630 unrecovered women were distinguished statistically from the 3102 recovered women by more frequent histories of allergies, rheumatoid disease, BCG immunization, Covid vaccination, strep throat and recent URIs, and both weight gain and weight losses of more than 5 kg in the 6 months following testing, and stressful events in the preceding year. Fatigue, pain, difficulty remembering, shortness of breath, heat and cold intolerance and unrefreshing sleep were reported in 41.9% to 10.5% of these 630 unrecovered women. Six months after confirmed SARS-CoV-2 infection 16.9% of Nepali women have long-COVID manifested as an immune, metabolic, and hormonal systems disruptive and dysfunction syndrome.}, } @article {pmid38465739, year = {2023}, author = {Guerrero-Romero, F and Gamboa-Gómez, CI and Rodríguez-Morán, M and Orrante, M and Rosales-Galindo, E and Cisneros-Ramírez, I and Arce-Quiñones, M and Orona-Díaz, K and Simental-Mendia, LE and Martínez-Aguilar, G}, title = {Hypomagnesemia and 25-hydroxyvitamin D deficiency in patients with long COVID.}, journal = {Magnesium research}, volume = {36}, number = {3}, pages = {30-36}, doi = {10.1684/mrh.2023.0519}, pmid = {38465739}, issn = {1952-4021}, mesh = {Adult ; Humans ; *Magnesium ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/complications ; Vitamin D/*analogs & derivatives ; Calcifediol ; }, abstract = {Clinical manifestations related to hypomagnesemia and/or deficiency of vitamin D are frequent in patients with an extended course of coronavirus disease-2019 (long COVID). To evaluate hypomagnesemia and hydroxyvitamin D deficiency in patients with long COVID. A total of 125 adults with a diagnosis of long COVID were enrolled in a cross-sectional study. Participants were allocated into a risk (hypomagnesemia and hydroxyvitamin D deficiency) or control (serum magnesium and hydroxyvitamin D within normal ranges) group. Hypomagnesemia and 25-hydroxyvitamin D deficiency were defined based on serum level ≤1.8 mg/dL and <30 ng/mL, respectively. The number of clinical manifestations of long COVID were significantly higher in the risk compared to the control group. Fatigue, memory loss, attention disorders, joint pain, anxiety, sleep disorders, myalgia, and depression, all of which are related to hypomagnesemia and/or 25-hydroxyvitamin D deficiency, were among the 10 most frequent manifestations in the risk group. The adjusted odds ratio for the association between hypomagnesemia and hydroxyvitamin D deficiency during long COVID was 3.1; 95% CI 2.3-12.4, p=0.005. Our results show that patients suffering with long COVID had a deficiency in magnesium and 25-hydroxyvitamin D which correlated with the number of associated clinical manifestations.}, } @article {pmid38465303, year = {2024}, author = {Hung, P and Brehon, K and Miciak, M and Brown, DA and Bostick, G and Brown, C and Churchill, K and Hall, M and Hoddinott, L and Hudon, A and Hunter, S and Perreault, K and Wieler, M and Skolnik, K and Lam, GY and Weatherald, J and Gross, DP}, title = {"I Had to Know About It, I Had to Find It, I Had to Know How to Access it": Experiences of Access to Rehabilitation Services Among People Living with Long COVID.}, journal = {Physiotherapy Canada. Physiotherapie Canada}, volume = {76}, number = {1}, pages = {8-24}, pmid = {38465303}, issn = {0300-0508}, abstract = {PURPOSE: The aim of this qualitative study is to understand the need for, access to, and quality of rehabilitation services for people living with Long COVID. Little is known about the experiences of people living with Long COVID accessing rehabilitation services. Therefore, we explored health concerns leading people living with Long COVID to seek help to address functional concerns and their experiences with accessing and participating in rehabilitation.

METHOD: Interpretive description guided exploration of participants' experiences with Long COVID rehabilitation in Alberta, Canada. Semi-structured interviews were completed with 56 participants recruited from: three publicly funded Long COVID clinics, a specialized private physiotherapy clinic, a telephone-based rehabilitation advice line, and a Workers' Compensation Board-funded Long COVID rehabilitation program. Recruitment through mass media coverage allowed us to include people who did not access rehabilitation services. Data analysis was informed by Braun and Clarke's reflexive thematic analysis.

RESULTS: Four themes were identified: (1) the burden of searching for guidance to address challenges with functioning and disability; (2) supportive relationships promote engagement in rehabilitation; (3) conditions for participation in safe rehabilitation; and (4) looking forward - provision of appropriate interventions at the right time.

CONCLUSIONS: Our findings highlight the experiences of accessing rehabilitation services for people living with Long COVID. Results suggest approaches to Long COVID rehabilitation should be accessible, multi-disciplinary, flexible, and person-centred.}, } @article {pmid38464139, year = {2024}, author = {Meijsen, J and Hu, K and Krebs, MD and Athanasiadis, G and Washbrook, S and Zetterberg, R and E Silva, RNA and Shorter, JR and Gådin, JR and Bergstedt, J and Howard, DM and Ye, W and , and Lu, Y and Valdimarsdóttir, UA and Ingason, A and Mikkelsen, DH and Plana-Ripoll, O and McGrath, JJ and Micali, N and Andreassen, OA and Werge, TM and Fang, F and Buil, A}, title = {Quantifying the Relative Importance of Genetics and Environment on the Comorbidity between Mental- and Cardiometabolic Disorders: A Comprehensive Analysis of National Register Data from 17 million Scandinavians.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38464139}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 MH123724/MH/NIMH NIH HHS/United States ; U01 MH094432/MH/NIMH NIH HHS/United States ; }, abstract = {Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with CMDs, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with CMDs was mainly or fully driven by environmental factors. These findings provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.}, } @article {pmid38463416, year = {2024}, author = {Agoston, DV}, title = {Traumatic Brain Injury in the Long-COVID Era.}, journal = {Neurotrauma reports}, volume = {5}, number = {1}, pages = {81-94}, pmid = {38463416}, issn = {2689-288X}, abstract = {Major determinants of the biological background or reserve, such as age, biological sex, comorbidities (diabetes, hypertension, obesity, etc.), and medications (e.g., anticoagulants), are known to affect outcome after traumatic brain injury (TBI). With the unparalleled data richness of coronavirus disease 2019 (COVID-19; ∼375,000 and counting!) as well as the chronic form, long-COVID, also called post-acute sequelae SARS-CoV-2 infection (PASC), publications (∼30,000 and counting) covering virtually every aspect of the diseases, pathomechanisms, biomarkers, disease phases, symptomatology, etc., have provided a unique opportunity to better understand and appreciate the holistic nature of diseases, interconnectivity between organ systems, and importance of biological background in modifying disease trajectories and affecting outcomes. Such a holistic approach is badly needed to better understand TBI-induced conditions in their totality. Here, I briefly review what is known about long-COVID/PASC, its underlying-suspected-pathologies, the pathobiological changes induced by TBI, in other words, the TBI endophenotypes, discuss the intersection of long-COVID/PASC and TBI-induced pathobiologies, and how by considering some of the known factors affecting the person's biological background and the inclusion of mechanistic molecular biomarkers can help to improve the clinical management of TBI patients.}, } @article {pmid38463084, year = {2024}, author = {Tariq, M and Mahak, F and Kumar, R and Kumar, A and Kumar, A and Khan, J and Muhammad, MA and Memon, U and Maqsood, KM and Tanveer, FS and Gill, A and Jawed, A and Shrestha, S and Waheed, MH}, title = {Unmasking the long-term effects: unravelling neuropsychiatric and neurological consequences of COVID-19.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {3}, pages = {1490-1495}, pmid = {38463084}, issn = {2049-0801}, abstract = {The COVID-19 pandemic has not only burdened healthcare systems but has also led to a new emerging medical enigma that is post-COVID-19 syndrome or "long COVID." Characterized by persistent symptoms that extend beyond the acute phase of the illness, long COVID has rapidly become a public health concern with ambiguous neurological and neuropsychiatric dimensions. This narrative review aims at synthesizing available research to decode the long-term impacts of COVID-19 on neurological and mental health. Drawing from a multitude of studies, this review synthesizes evidence on various neuropsychiatric and neurological symptoms, including cognitive deficits, mood disorders, and more. The narrative delves into potential pathogenic mechanisms, hoping to fill existing research gaps and offering directions for future inquiry. The objective is not just academic; it has immediate real-world implications. Understanding these long-term effects is crucial for developing effective treatments and interventions, thereby better serving the millions of individuals living with these lingering symptoms. As healthcare systems continue to grapple with the fallout from the pandemic, this review provides much-needed context and insights into an area that demands urgent research and action.}, } @article {pmid38462511, year = {2024}, author = {Manaka, K and Kato, S and Sakamoto, R and Yamakage, H and Uema, T and Kawai, S and Shibata, M and Hiratsuka, I and Nakachi, S and Onoue, T and Tsuchiya, T and Fukui, M and Hashimoto, K and Suzuki, A and Makita, N and Ogawa, Y and Arima, H and Satoh-Asahara, N and Masuzaki, H}, title = {Impact of coronavirus disease 2019 on medical practice in endocrine and metabolic diseases in Japan: a nationwide surveillance study conducted by the Japan Endocrine Society.}, journal = {Endocrine journal}, volume = {71}, number = {5}, pages = {499-514}, doi = {10.1507/endocrj.EJ23-0671}, pmid = {38462511}, issn = {1348-4540}, mesh = {Humans ; *COVID-19/epidemiology ; Japan/epidemiology ; Cross-Sectional Studies ; *Metabolic Diseases/epidemiology ; *Endocrine System Diseases/epidemiology/therapy ; Surveys and Questionnaires ; Female ; Male ; *SARS-CoV-2 ; Societies, Medical ; Endocrinologists ; Adult ; Middle Aged ; Endocrinology/organization & administration ; Practice Patterns, Physicians'/statistics & numerical data ; }, abstract = {We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.}, } @article {pmid38461701, year = {2024}, author = {van der Knaap, N and Ariës, MJH and van der Horst, ICC and Jansen, JFA}, title = {On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review.}, journal = {NeuroImage. Clinical}, volume = {42}, number = {}, pages = {103589}, pmid = {38461701}, issn = {2213-1582}, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; SARS-CoV-2 ; }, abstract = {Many Coronavirus Disease 2019 (COVID-19) patients are suffering from long-term neuropsychological sequelae. These patients may benefit from a better understanding of the underlying neuropathophysiological mechanisms and identification of potential biomarkers and treatment targets. Structural clinical neuroimaging techniques have limited ability to visualize subtle cerebral abnormalities and to investigate brain function. This scoping review assesses the merits and potential of advanced neuroimaging techniques in COVID-19 using literature including advanced neuroimaging or postmortem analyses in adult COVID-19 patients published from the start of the pandemic until December 2023. Findings were summarized according to distinct categories of reported cerebral abnormalities revealed by different imaging techniques. Although no unified COVID-19-specific pattern could be subtracted, a broad range of cerebral abnormalities were revealed by advanced neuroimaging (likely attributable to hypoxic, vascular, and inflammatory pathology), even in absence of structural clinical imaging findings. These abnormalities are validated by postmortem examinations. This scoping review emphasizes the added value of advanced neuroimaging compared to structural clinical imaging and highlights implications for brain functioning and long-term consequences in COVID-19.}, } @article {pmid38460898, year = {2024}, author = {Faghy, MA and Duncan, R and Hume, E and Gough, L and Roscoe, C and Laddu, D and Arena, R and Asthon, REM and Dalton, C}, title = {Developing effective strategies to optimize physical activity and cardiorespiratory fitness in the long Covid population- The need for caution and objective assessment.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {62-70}, doi = {10.1016/j.pcad.2024.03.003}, pmid = {38460898}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness ; COVID-19/complications ; *Exercise ; *Post-Acute COVID-19 Syndrome/diagnosis/pathology/therapy ; Quality of Life ; }, abstract = {The Post Covid-19 Condition (commonly known as Long Covid) has been defined by the World Health Organisation as occurring in individuals with a history of probable or confirmed SARS CoV 2 infection, usually within 3 months from the onset of acute Covid-19 infection with symptoms that last for at least two months which cannot be explained by an alternative diagnosis. Long Covid is associated with over two hundred recognised symptoms and affects tens of millions of people worldwide. Widely reported reductions in quality of life(QoL) and functional status are caused by extremely sensitive and cyclical symptom profiles that are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli. This manifestation prevents millions of people from engaging in routine activities of daily living (ADLs) and has important health and well-being, social and economic impacts. Post-exertional symptom exacerbation (PESE) (also known as post-exertional malaise) is an exacerbation in the severity of fatigue and other symptoms following physical, emotional, orthostatic and cognitive tasks. Typically, this will occur 24-72 h after "over-exertion" and can persist for several days and even weeks. It is a hallmark symptom of Long Covid with a reported prevalence of 86%. The debilitating nature of PESE prevents patients from engaging in physical activity which impacts functional status and QoL. In this review, the authors present an update to the literature relating to PESE in Long Covid and make the case for evidence-based guidelines that support the design and implementation of safe rehabilitation approaches for people with Long Covid. This review also considers the role of objective monitoring to quantify a patient's response to external stimuli which can be used to support the safe management of Long Covid and inform decisions relating to engagement with any stimuli that could prompt an exacerbation of symptoms.}, } @article {pmid38460395, year = {2024}, author = {Peluso, MJ and Abdel-Mohsen, M and Henrich, TJ and Roan, NR}, title = {Systems analysis of innate and adaptive immunity in Long COVID.}, journal = {Seminars in immunology}, volume = {72}, number = {}, pages = {101873}, doi = {10.1016/j.smim.2024.101873}, pmid = {38460395}, issn = {1096-3618}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; SARS-CoV-2 ; Adaptive Immunity ; Systems Analysis ; Immunity, Innate ; }, abstract = {Since the onset of the COVID-19 pandemic, significant progress has been made in developing effective preventive and therapeutic strategies against severe acute SARS-CoV-2 infection. However, the management of Long COVID (LC), an infection-associated chronic condition that has been estimated to affect 5-20% of individuals following SARS-CoV-2 infection, remains challenging due to our limited understanding of its mechanisms. Although LC is a heterogeneous disease that is likely to have several subtypes, immune system disturbances appear common across many cases. The extent to which these immune perturbations contribute to LC symptoms, however, is not entirely clear. Recent advancements in multi-omics technologies, capable of detailed, cell-level analysis, have provided valuable insights into the immune perturbations associated with LC. Although these studies are largely descriptive in nature, they are the crucial first step towards a deeper understanding of the condition and the immune system's role in its development, progression, and resolution. In this review, we summarize the current understanding of immune perturbations in LC, covering both innate and adaptive immune responses, and the cytokines and analytes involved. We explore whether these findings support or challenge the primary hypotheses about LC's underlying mechanisms. We also discuss the crosstalk between various immune system components and how it can be disrupted in LC. Finally, we emphasize the need for more tissue- and subtype-focused analyses of LC, and for enhanced collaborative efforts to analyze common specimens from large cohorts, including those undergoing therapeutic interventions. These collective efforts are vital to unravel the fundaments of this new disease, and could also shed light on the prevention and treatment of the larger family of chronic illnesses linked to other microbial infections.}, } @article {pmid38459313, year = {2024}, author = {Susan Varghese, V}, title = {Awareness among healthcare professionals of long COVID oral manifestations.}, journal = {British dental journal}, volume = {236}, number = {5}, pages = {391}, doi = {10.1038/s41415-024-7209-y}, pmid = {38459313}, issn = {1476-5373}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Health Personnel ; Awareness ; Delivery of Health Care ; }, } @article {pmid38458800, year = {2024}, author = {Chen, X and Norris, C and Whitten, T and Ho, C and Mann, B and Bakal, J}, title = {Symptomology following COVID-19 among adults in Alberta, Canada: an observational survey study.}, journal = {BMJ open}, volume = {14}, number = {3}, pages = {e078119}, pmid = {38458800}, issn = {2044-6055}, mesh = {Adult ; Middle Aged ; Humans ; Female ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Alberta/epidemiology ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; Pandemics ; Headache/etiology/complications ; Self Report ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVE: Fatigue, headache, problems sleeping and numerous other symptoms have been reported to be associated with long COVID. However, many of these symptoms coincide with symptoms reported by the general population, possibly exacerbated by restrictions/precautions experienced during the COVID-19 pandemic. This study examines the symptoms reported by individuals who tested positive for COVID-19 compared with those who tested negative.

DESIGN: Observational study.

SETTING: The study was conducted on adult residents in Alberta, Canada, from October 2021 to February 2023.

PARTICIPANTS: We evaluated self-reported symptoms in 7623 adults with positive COVID-19 tests and 1520 adults who tested negative, using surveys adapted from the internationally standardised International Severe Acute Respiratory and emerging Infection Consortium (ISARIC)-developed COVID-19 long-term follow-up tools. These individuals had an index COVID-19 test date between 1 March 2020 and 31 December 2022 and were over 28 days post-COVID-19 testing.

PRIMARY OUTCOME MEASURES: The primary outcomes were to identify the symptoms associated with COVID-19 positivity and risk factors for reporting symptoms.

RESULTS: Fatigue was the top reported symptom (42%) among COVID-19-positive respondents, while headache was the top reported symptom (32%) in respondents who tested negative. Compared with those who tested negative, COVID-19-positive individuals reported 1.5 times more symptoms and had higher odds of experiencing 31 out of the 40 listed symptoms during the postinfectious period. These symptoms included olfactory dysfunction, menstruation changes, cardiopulmonary and neurological symptoms. Female sex, middle age (41-55 years), Indigeneity, unemployment, hospital/intensive care unit (ICU) admission at the time of testing and pre-existing health conditions independently predicted a greater number and variety of symptoms.

CONCLUSIONS: Our results provide evidence that COVID-19 survivors continue to experience a significant number and variety of symptoms. These findings can help inform targeted strategies for the unequally affected population. It is important to offer appropriate management for symptom relief to those who have survived the acute COVID-19 illness.}, } @article {pmid38458016, year = {2024}, author = {Emerson, ND and Lavretsky, H and Pittman, WQ and Viswanathan, N and Siddarth, P}, title = {An open trial of biofeedback for long COVID.}, journal = {Journal of psychosomatic research}, volume = {179}, number = {}, pages = {111625}, doi = {10.1016/j.jpsychores.2024.111625}, pmid = {38458016}, issn = {1879-1360}, support = {K24 AT009198/AT/NCCIH NIH HHS/United States ; }, mesh = {Adult ; Humans ; Biofeedback, Psychology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: Biofeedback is a therapeutic treatment model that teaches self-regulation of autonomic functions to alleviate stress-related symptoms. "Long COVID" refers to chronic physical and cognitive sequelae post-SARS-CoV-2 infection. This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID.

METHODS: Data were collected from 20 adult participants aged 22-63 (Mage = 44.1, SDage = 12.2) with varying long COVID symptoms. Within this single arm design, 16 of the 20 participants completed all six sessions of biofeedback; 14 completed an assessment at the three-month post-treatment time point.

RESULTS: Participants self-reported significant improvements in somatic, anxiety, and depressive symptoms, sleep quality, quality of life, and number of "bad days" immediately after the intervention and three months later (Cohen's d effect size (ES) = 1.09-0.46). Reduced number of medical doctor visits (ES = 0.85) and prescription drug use over the last month (odds ratio = 0.33), as well as improved emotional wellbeing (ES = 0.97) were observed at the three-month time point only.

CONCLUSION: Results suggest that this short, readily scalable intervention can be potentially efficacious in alleviating symptoms of long COVID. Despite notable improvements, the major limitation of this study is its lack of control group. While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection.

CLINICALTRIALS: govID: NCT05120648.}, } @article {pmid38456315, year = {2024}, author = {Lee, C and Greenwood, DC and Master, H and Balasundaram, K and Williams, P and Scott, JT and Wood, C and Cooper, R and Darbyshire, JL and Gonzalez, AE and Davies, HE and Osborne, T and Corrado, J and Iftekhar, N and Rogers, N and Delaney, B and Greenhalgh, T and Sivan, M and , }, title = {Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29486}, doi = {10.1002/jmv.29486}, pmid = {38456315}, issn = {1096-9071}, support = {//National Institute for Health and Care Research/ ; }, mesh = {United States ; Humans ; *Orthostatic Intolerance/epidemiology/complications/diagnosis ; Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology/complications ; *Postural Orthostatic Tachycardia Syndrome/complications/diagnosis ; }, abstract = {Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.}, } @article {pmid38455946, year = {2023}, author = {Brus, IM and Spronk, I and Haagsma, JA and de Groot, A and Tieleman, P and Biere-Rafi, S and Polinder, S}, title = {The prolonged impact of COVID-19 on symptoms, health-related quality of life, fatigue and mental well-being: a cross-sectional study.}, journal = {Frontiers in epidemiology}, volume = {3}, number = {}, pages = {1144707}, pmid = {38455946}, issn = {2674-1199}, abstract = {BACKGROUND: A subset of patients experience persisting symptoms after an acute COVID-19 infection, referred to as "post COVID-19 condition". This cross-sectional study aimed to compare symptoms, health-related quality of life (HRQoL), fatigue, mental well-being, and determinants of diminished HRQoL, between patients with post COVID-19 condition categorized by time since acute infection.

METHODS: We performed an online survey and analyzed responses of 10,194 adult respondents with a confirmed or suspected COVID-19 infection, who experienced persisting symptoms ≥3 months after the initial infection. The most debilitating symptoms and health outcomes were studied separately for respondents 3-6, 7-9, 10-12, 13-18, 19-24, and >24 months after acute infection.

RESULTS: At each time period, fatigue, sensory-processing problems, and concentration problems were the most debilitating symptoms reported by respondents, although the proportion of respondents who reported these symptoms differed significantly between time periods. Respondents 3-6 months post-acute infection had the lowest HRQoL (median EQ-5D utility score: 0.59), the highest fatigue level (median score: 110.0) and the highest proportion with a likely depressive disorder (32.4%), whereas respondents 13-18 months post-infection had the highest HRQoL (0.65), the lowest fatigue level (106.0), and the second lowest proportion with a likely depressive disorder (25.0%) (p = 0.000-0.007). Compared to those 13-18 and 19-24 months post-infection, respondents >24 months post-infection had a slightly lower HRQoL (0.60), lower fatigue level (108.0), and lower proportion with a likely depressive disorder (29.2%), although only the differences in HRQoL were statistically significant (p = 0.001-0.010). Younger age, female gender, lower level of education, not having paid work before COVID-19, comorbidity, and not being vaccinated, seemed to be associated with lower HRQoL.

CONCLUSION: Regardless of time since infection, respondents considered fatigue, sensory processing problems and concentration problems the most debilitating symptoms. They experienced a low HRQoL and severe fatigue, even more than two years after acute COVID-19 infection. Respondents 3-6 months post-infection had the worst health outcomes, whereas respondents 13-18 months post-infection had the best outcomes, indicating that, at least for a subgroup of patients, health status may improve over time.}, } @article {pmid38455892, year = {2023}, author = {Gómez Bravo, R and Infanti, A and Billieux, J and Ritzen, M and , and Vögele, C and Benoy, C}, title = {The psychological syndrome associated with Long-COVID: A study protocol.}, journal = {Frontiers in epidemiology}, volume = {3}, number = {}, pages = {1193369}, pmid = {38455892}, issn = {2674-1199}, abstract = {INTRODUCTION: Chronic post-viral syndromes, including Long-COVID, are characterized by a range of persistent symptoms that occur following a viral infection. Psychological symptoms are prevalent in Long-COVID patients and can have a significant impact on their quality of life. However, the specific patterns of psychological symptoms, their associations with physical symptoms, and the factors predicting their severity remain poorly understood.

AIMS: This study aims to explore and systematically assess psychological symptoms in Long-COVID, to identify syndrome clusters based on these symptoms, to examine their relationship with physical symptoms, and to investigate the influence of pandemic-related variables.

METHODS: Descriptive, cross-sectional study with data collected through an online questionnaire across several EU countries, from February 2020 to December 2022. Participants were recruited using public relations, the social media and information campaigns directed at the public and health professionals using snowball sampling.

RESULTS: The findings will allow to phenotype Long-COVID related psychological symptom clusters based on self-reports. facilitating improved assessment and treatment approaches.

CONCLUSIONS: The results will provide important knowledge for the public health management of the public healh management of Long COVID. The findings will contribute to a better understanding of the psychological symptoms associated with Long-COVID and the development of specific treatment guidelines for psychological burden associated with Long-COVID, thereby supporting management strategies to combat the after-effects of the COVID-19 pandemic, enhancing their overall well-being and quality of life.}, } @article {pmid38455739, year = {2024}, author = {Zhang, J and Kuang, T and Liu, X}, title = {Advances in researches on long coronavirus disease in children: a narrative review.}, journal = {Translational pediatrics}, volume = {13}, number = {2}, pages = {318-328}, pmid = {38455739}, issn = {2224-4344}, abstract = {BACKGROUND AND OBJECTIVE: In the context of the global pandemic of coronavirus disease 2019 (COVID-19), more than 700 million infections and millions of deaths have occurred in countries around the world. Currently, two main sequelae of this disease are considered to occur in children, namely, multi-system inflammatory syndrome in children and long COVID. Among these two, the incidence of long COVID is higher and its impact on the population is more extensive, which is the focus of us. However, due to the lack of relevant studies and the limitations of most studies, the studies on sequelae of COVID-19 infection lag behind those of adults, but they have begun to attract the attention of some clinicians and researchers. We aim to summarize the current knowledge of long COVID in children, helping pediatricians and researchers to better understand this disease and providing guidance on research and clinical treatment of it.

METHODS: We reviewed all the studies on "long COVID", pediatric, children, adolescent, post-COVID syndrome in PubMed published after 2019.

KEY CONTENT AND FINDINGS: This review summarizes the latest researches on epidemiology, pathogenesis, clinical manifestations, prevention and treatment of long COVID in children. Based on the existing research data, we summarized and analyzed the characteristics of long COVID in children, discovering the means to decipher the diagnosis of COVID-19 in children and some potential therapeutic treatments.

CONCLUSIONS: We aim to summarize existing research on long COVID in children and help pediatricians and government agencies quickly understand the disease so that it can be used for clinical diagnosis, treatment and prevention in the population. In addition, providing a research basis for further researches on the cellular and even molecular level to explain the occurrence and development of diseases, and has a guiding role for future research direction.}, } @article {pmid38455611, year = {2023}, author = {Aritonang, ME and Pandia, P and Pradana, A and Ashar, T}, title = {Factors associated with small airway obstruction in COVID-19 survivors: A cross-sectional study among health-care providers.}, journal = {Narra J}, volume = {3}, number = {3}, pages = {e437}, pmid = {38455611}, issn = {2807-2618}, abstract = {Coronavirus disease 2019 (COVID-19) has been identified for more than two years, yet studies assessing post-infection lung function are limited. Reports on lung function in COVID-19 patients indicate that patients have restrictive defects and small airway dysfunction that can persist and are not necessarily related to the severity of the disease. The aim of this study was to assess the incidence of small airway obstruction and its incidence-associated factors among COVID-19 survivors to better describe the long-term effects of COVID-19. A cross-sectional study was conducted among COVID-19 survivors who less than 50 years at Medan Adventist Hospital between 2020-2022. The data were collected through interview, direct assessment and respiratory examination. A total of 89 COVID-19 survivors were recruited of which the majority of them were female with a mean age of 32.6-year-old with the largest group was 19-30 years. The comorbidities found among the survivors were heart and thyroid disorders, with the most common symptom of post-COVID-19 was fatigue. Most of them had mild COVID-19. The mean forced mid-expiratory flow (FEF25-75%) was 96.3±20.22, with an incidence rate of small airway obstruction was 19.1%. Univariate and multivariate analyses indicated no significant association between age, gender, comorbidities, history of oxygenation during COVID-19 treatment, COVID-19 severity and the type of post COVID-19 syndrome symptoms with the incidence of small airway obstruction. In conclusion, among COVID-19 survivors who were less than 50 years old, those studied variables seems have less association with the incidence of small airway obstruction. Nevertheless, a further study with a bigger sample size is important to be conducted.}, } @article {pmid38455472, year = {2024}, author = {Eduvirgem, J and Bressan, J and Hermsdorff, HHM and Montenegro, LC and Brandão, ML and Neves, AAT and da Silva, LSA and Gerake-Dias, TA and Pimenta, AM}, title = {Risk and protective factors for Long COVID in Brazilian adults (CUME Study).}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1344011}, pmid = {38455472}, issn = {2296-858X}, abstract = {BACKGROUND: Most people recover from COVID-19, however, between 5 to 20% have experienced new, recurring, or continuous health problems four or more weeks after being infected, a phenomenon called Long COVID, and whose reasons for its manifestation are incipient. Our objective was to analyse the risk and protective factors for Long COVID in Brazilian adults participating in the CUME Study.

METHODS: The CUME Study is a prospective cohort conducted with graduates from federal universities in the State of Minas Gerais, Brazil. In this study, 390 participants who answered the baseline questionnaire in 2016 and the third follow-up questionnaire in 2022 (which contained a block of questions about occurrence of COVID-19 and Long COVID) were included. The diagnosis of Long COVID was based on self-reporting of persistence of signs and symptoms of COVID-19 between 30 days and 6 months after remission of the disease. To estimate the risk and protective factors for Long COVID, a hierarchical multivariate statistical analysis was conducted using the Poisson regression technique.

RESULTS: Long COVID was observed in 48.9% of the participants. The following characteristics were identified as risk factors for the outcome: female sex (RR = 1.56; 95% CI = 1.22-1.99); prior diagnosis of hypertension (RR = 1.46; 95% CI = 1.19-1.80); having contracted COVID-19 in the first (RR =1.38; 95% CI = 1.07-1.79) or in the second waves (RR = 1.33; 95% CI = 1.07-1.65) of the pandemic period; and having presented three or more signs and symptoms during the acute phase of COVID-19 (RR = 2.99; 95% CI = 1.08-8.24). On the other hand, having a doctoral/postdoctoral educational level (RR = 0.69; 95% CI = 0.50-0.94) was identified as a protective factor for the outcome.

CONCLUSION: Health system managers and healthcare professionals should be aware of the socioeconomic profile and disease history of patients who have had COVID-19 because women, people with a prior diagnosis of hypertension, and those who manifested multiple signs and symptoms of COVID-19 during the acute phase of the disease were at greater risk of developing Long COVID.}, } @article {pmid38455320, year = {2022}, author = {Müller, D and Stengel, S and Roesler, M and Schillinger, G and Dräther, H and Günster, C and Tillmanns, H and Erhart, M and Szecsenyi, J and Merle, U}, title = {Treated post-acute sequelae after COVID-19 in a German matched cohort study using routine data from 230,256 adults.}, journal = {Frontiers in epidemiology}, volume = {2}, number = {}, pages = {1089076}, pmid = {38455320}, issn = {2674-1199}, abstract = {BACKGROUND: Post-acute sequelae after COVID-19 are still associated with knowledge gaps and uncertainties at the end of 2022, e.g., prevalence, pathogenesis, treatment, and long-term outcomes, and pose challenges for health providers in medical management. The aim of this study was to contribute to the understanding of the multi-faceted condition of long-/ post-COVID. It was designed to evaluate whether a prior SARS-CoV-2 infection during the first COVID-19 wave in Germany increases the rate of disease, as measured via a record of insurance data on diagnoses, symptoms, and treatment, in the subsequent 12 months compared with matched control groups without recorded SARS-CoV-2 infection.

METHOD: 50 outcome variables at disease, symptom and treatment levels (14 main categories and 36 sub-categories; new diagnoses) were defined from health insurance data. Logistic regression was carried out for two groups of patients tested positive in a PCR test in March/April 2020 for SARS-CoV-2, compared to the respective risk-adjusted (age, administrative region, 1:5 propensity-score matching), contemporaneous control group without prior documented SARS-CoV-2 infection (CG): First, individuals with outpatient treatment of acute COVID-19, indicating a not severe course (COV-OUT), and second, individuals with inpatient treatment of acute COVID-19, indicating a severe course (COV-IN) were compared with their respective control group.

RESULTS: The mortality rate in COV-OUT (n = 32,378) and COV-IN (n = 5,998) groups is higher compared to their control groups with odds ratio (OR) 1.5 [95%CI (1.3, 1.6)] and 1.7 [95%CI (1.5, 1.8)] respectively. Both groups were more likely to have experienced at least one outcome compared to their CG [OR = 1.4, 95%CI (1.4, 1.4)]; OR = 2.5, 95%CI [2.4, 2.6]). 42/37 (COV-IN/COV-OUT) outcome variables showed increased ORs. COV-OUT: Loss of taste and smell [OR = 5.8, 95%CI (5.1, 6.6)], interstitial respiratory diseases [OR = 2.8, 95%CI (2.0, 4.1)] and breathing disorders [OR = 3.2, 95%CI (2.2, 4.7)] showed the highest ORs. COV-IN: Interstitial respiratory diseases [OR = 12.2, 95%CI (8.5, 17.5)], oxygen therapy [OR = 8.1, 95%CI (6.4, 10.2)] and pulmonary embolism/anticoagulation [OR = 5.9, 95%CI (4.4, 7.9)] were the most pronounced.

CONCLUSION: Following a SARS-CoV-2 infection during the first wave of the COVID-19 pandemic in Germany, 8.4 [COV-OUT, 95%CI (7.7, 9.1)] respectively 25.5 [COV-IN, 95%CI (23.6, 27.4)] percentage points more subjects showed at least one new diagnosis/symptom/treatment compared to their matched CG (COV-OUT: 44.9%, CG: 36.5%; COV-IN: 72.0%, CG: 46.5%). Because the symptoms and diagnoses are so varied, interdisciplinary and interprofessional cooperation among those providing management is necessary.}, } @article {pmid38454468, year = {2024}, author = {Preßler, H and Machule, ML and Ufer, F and Bünger, I and Li, LY and Buchholz, E and Werner, C and Beraha, E and Wagner, F and Metz, M and Burock, S and Bruckert, L and Franke, C and Wilck, N and Krüger, A and Reshetnik, A and Eckardt, KU and Endres, M and Prüss, H}, title = {IA-PACS-CFS: a double-blinded, randomized, sham-controlled, exploratory trial of immunoadsorption in patients with chronic fatigue syndrome (CFS) including patients with post-acute COVID-19 CFS (PACS-CFS).}, journal = {Trials}, volume = {25}, number = {1}, pages = {172}, pmid = {38454468}, issn = {1745-6215}, mesh = {Humans ; Canada ; *COVID-19/therapy ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition which markedly restricts activity and function of affected people. Since the beginning of the COVID-19 pandemic ME/CFS related to post-acute COVID-19 syndrome (PACS) can be diagnosed in a subset of patients presenting with persistent fatigue 6 months after a mostly mild SARS-CoV-2 infection by fulfillment of the Canadian Consensus Criteria (CCC 2003). Induction of autoimmunity after viral infection is a mechanism under intensive investigation. In patients with ME/CFS, autoantibodies against thyreoperoxidase (TPO), beta-adrenergic receptors (ß2AR), and muscarinic acetylcholine receptors (MAR) are frequently found, and there is evidence for effectiveness of immunomodulation with B cell depleting therapy, cyclophosphamide, or intravenous immunoglobulins (IVIG). Preliminary studies on the treatment of ME/CFS patients with immunoadsorption (IA), an apheresis that removes antibodies from plasma, suggest clinical improvement. However, evidence from placebo-controlled trials is currently missing.

METHODS: In this double-blinded, randomized, sham-controlled, exploratory trial the therapeutic effect of five cycles of IA every other day in patients with ME/CFS, including patients with post-acute COVID-19 chronic fatigue syndrome (PACS-CFS), will be evaluated using the validated Chalder Fatigue Scale, a patient-reported outcome measurement. A total of 66 patients will be randomized at a 2:1 ratio: 44 patients will receive IA (active treatment group) and 22 patients will receive a sham apheresis (control group). Moreover, safety, tolerability, and the effect of IA on patient-reported outcome parameters, biomarker-related objectives, cognitive outcome measurements, and physical parameters will be assessed. Patients will be hospitalized at the clinical site from day 1 to day 10 to receive five IA treatments and medical visits. Four follow-up visits (including two visits at site and two visits via telephone call) at month 1 (day 30), 2 (day 60), 4 (day 120), and 6 (day 180; EOS, end of study visit) will take place.

DISCUSSION: Although ME/CFS including PACS-CFS causes an immense individual, social, and economic burden, we lack efficient therapeutic options. The present study aims to investigate the efficacy of immunoadsorption and to contribute to the etiological understanding and establishment of diagnostic tools for ME/CFS.

TRIAL REGISTRATION: Registration Number: NCT05710770 . Registered on 02 February 2023.}, } @article {pmid38454462, year = {2024}, author = {Lin, Y and Yang, Y and Xiang, N and Wang, L and Zheng, T and Zhuo, X and Shi, R and Su, X and Liu, Y and Liao, G and Du, L and Huang, J}, title = {Characterization and trajectories of hematological parameters prior to severe COVID-19 based on a large-scale prospective health checkup cohort in western China: a longitudinal study of 13-year follow-up.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {105}, pmid = {38454462}, issn = {1741-7015}, support = {32101206//National Natural Science Foundation of China/ ; 32171285//National Natural Science Foundation of China/ ; 2023YFS0025//Key Program of Science and Technology Department of Sichuan Province/ ; 2023YFS0102//Key Program of Science and Technology Department of Sichuan Province/ ; 2023HXFH044//Innovative Research Group Project of the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Longitudinal Studies ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; }, abstract = {BACKGROUND: The relaxation of the "zero-COVID" policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19.

METHODS: Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells.

RESULTS: A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066-18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046-1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341-0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009-6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P < 0.05).

CONCLUSIONS: Our findings might help decision-makers and clinicians to classify different risk groups of population due to outbreaks including COVID-19. They could not only optimize the allocation of medical resources, but also help them be more proactive instead of reactive to long COVID-19 or even other outbreaks in the future.}, } @article {pmid38454352, year = {2024}, author = {King, JP and Chung, JR and Donahue, JG and Martin, ET and Leis, AM and Monto, AS and Gaglani, M and Dunnigan, K and Raiyani, C and Saydah, S and Flannery, B and Belongia, EA}, title = {Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {300}, pmid = {38454352}, issn = {1471-2334}, support = {K12 TR004374/TR/NCATS NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Humans ; *SARS-CoV-2 ; Outpatients ; *COVID-19/diagnosis ; COVID-19 Testing ; COVID-19 Vaccines ; Dyspnea ; Fatigue ; }, abstract = {BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination.

METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression.

RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model.

CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.}, } @article {pmid38453677, year = {2024}, author = {Kleine, N and Kwan, ATH and Le, GH and Guo, Z and Phan, L and Subramaniapillai, M and McIntyre, RS}, title = {Impact of Baseline Anxiety on Well-being in People with Post-COVID-19 Condition: A Secondary Analysis.}, journal = {CNS spectrums}, volume = {29}, number = {2}, pages = {150-154}, doi = {10.1017/S1092852924000099}, pmid = {38453677}, issn = {1092-8529}, mesh = {Humans ; *COVID-19 ; *Depressive Disorder, Major ; Anxiety Disorders/epidemiology/prevention & control ; Anxiety ; Vortioxetine ; }, abstract = {BACKGROUND: Post-COVID-19 condition (PCC) is associated with a host of psychopathological conditions including prominent anxiety symptoms. However, it is not known what effect anxious symptoms have on measures of well-being in individuals living with PCC. This study aims to evaluate anxiety's association with measures of well-being in people with PCC.

METHODS: This is a post hoc analysis utilizing data from a placebo-controlled, randomized, double-blind clinical trial assessing the effect of vortioxetine on cognitive impairment in individuals with PCC (NCT05047952). Baseline data with respect to anxiety and well-being were collected using the Generalized Anxiety Disorder Scale, 7-Item (GAD-7), and the World Health Organization (WHO) Well-Being Index, 5-Item (WHO-5), respectively. A generalized linear model (GLM) analysis on baseline GAD-7 and WHO-5 scores was conducted with age, sex, employment status, education level, previous major depressive disorder (MDD) diagnosis, and confirmed COVID-19 cases as covariates.

RESULTS: Data was analyzed in a sample of 144 participants (N = 144). After controlling for the aforementioned covariates, the results found that GAD-7 and WHO-5 scores had a significant negative correlation (β = -0.053, p = <0.001), signifying that increased anxiety had adverse effects on the overall well-being of individuals with PCC.

CONCLUSION: Herein, we observed a clinically meaningful level of anxiety in individuals with PCC. We also identified a robust correlation between anxiety in PCC and measures of general well-being. Our results require replication, providing the impetus for recommending screening and targeting anxious symptoms as a tactic to improve general well-being and outcomes in individuals with PCC.}, } @article {pmid38453258, year = {2024}, author = {Gerayeli, FV and Eddy, RL and Sin, DD}, title = {A proposed approach to pulmonary long COVID: a viewpoint.}, journal = {The European respiratory journal}, volume = {64}, number = {3}, pages = {}, pmid = {38453258}, issn = {1399-3003}, mesh = {Humans ; *COVID-19/epidemiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; }, abstract = {A majority of patients with pulmonary long COVID have small airway disease, characterised by inflammation, which can be diagnosed with traditional and emerging technologies https://bit.ly/48WceB3}, } @article {pmid38451416, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Catahay, JA and Macasaet, R and Velasco, JV and Macapagal, S and Caldararo, M and Henry, BM and Lippi, G and Franco-Moreno, A and Notarte, KI}, title = {Correction: Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.}, journal = {Infection}, volume = {52}, number = {5}, pages = {1687}, doi = {10.1007/s15010-024-02208-x}, pmid = {38451416}, issn = {1439-0973}, } @article {pmid38450272, year = {2023}, author = {Widasari, N and Heriansyah, T and Ridwan, M and Munirwan, H and Kurniawan, FD}, title = {Correlation between high sensitivity C reactive protein (Hs-CRP) and neutrophil-to- lymphocyte ratio (NLR) with functional capacity in post COVID-19 syndrome patients.}, journal = {Narra J}, volume = {3}, number = {2}, pages = {e183}, pmid = {38450272}, issn = {2807-2618}, abstract = {Post coronavirus disease 2019 (COVID-19) syndrome is one of the causes of reduced functional capacity and work productivity, in particular for healthcare workers. The pathophysiology of the post COVID-19 syndrome is related to complex and multisystem inflammatory mechanisms, and cardiopulmonary exercise rehabilitation program is one of the efforts to improve the recovery process for patients with post COVID-19 syndrome. The aim of this study was to determine the correlation between the level of high sensitivity C-reactive protein (Hs-CRP) and neutrophil-to-lymphocyte ratio (NLR) with functional capacity (VO2max) in individuals with post-COVID-19 syndrome who received moderate- and high-intensity supervised cardiopulmonary exercise. A prospective cohort study was conducted at the Integrated Cardiac Rehabilitation Center of Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia. The supervised cardiopulmonary exercise was conducted for six weeks according to the participant's baseline VO2max. Spearman's and Pearson's correlation tests were used to assess the correlations. A total of 30 individuals (19 and 11 had moderate and high intensity exercise, respectively) were involved in this study. At moderate intensity exercise, the average Hs-CRP and NLR were 3.3 mg/L and 1.99, respectively; while at high intensity, the values were 3.8 mg/L and 1.79, respectively. No significant correlation between Hs-CRP level and functional capacity in both moderate-intensity and high intensity groups. In contrast, NLR was negatively correlated with functional capacity (r=-0.545, p=0.016) in moderate intensity exercise group. In conclusion, NLR value was negatively correlated with functional capacity in individuals with post-COVID-19 syndrome after receiving moderate intensity supervised cardiopulmonary exercise program. Therefore, moderate intensity of cardiopulmonary exercise maybe be used as a program to accelerate the recovery for those with post COVID-19 syndrome.}, } @article {pmid38450231, year = {2024}, author = {Guerra, G and Lucariello, A and Komici, K}, title = {Editorial: Long COVID: nutrition and lifestyle changes.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1375449}, pmid = {38450231}, issn = {2296-861X}, } @article {pmid38450137, year = {2024}, author = {Wilton, J and Abdulmenan, J and Chong, M and Becerra, A and Najmul Hussain, M and Harrigan, SP and Velásquez García, HA and Naveed, Z and Sbihi, H and Smolina, K and Taylor, M and Adhikari, B and Zandy, M and Setayeshgar, S and Li, J and Abdia, Y and Binka, M and Rasali, D and Rose, C and Coss, M and Flatt, A and Mussavi Rizi, SA and Janjua, NZ}, title = {Cohort profile: the British Columbia COVID-19 Cohort (BCC19C)-a dynamic, linked population-based cohort.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1248905}, pmid = {38450137}, issn = {2296-2565}, mesh = {Male ; Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; British Columbia/epidemiology ; Pandemics ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {PURPOSE: The British Columbia COVID-19 Cohort (BCC19C) was developed from an innovative, dynamic surveillance platform and is accessed/analyzed through a cloud-based environment. The platform integrates recently developed provincial COVID-19 datasets (refreshed daily) with existing administrative holdings and provincial registries (refreshed weekly/monthly). The platform/cohort were established to inform the COVID-19 response in near "real-time" and to answer more in-depth epidemiologic questions.

PARTICIPANTS: The surveillance platform facilitates the creation of large, up-to-date analytic cohorts of people accessing COVID-19 related services and their linked medical histories. The program of work focused on creating/analyzing these cohorts is referred to as the BCC19C. The administrative/registry datasets integrated within the platform are not specific to COVID-19 and allow for selection of "control" individuals who have not accessed COVID-19 services.

FINDINGS TO DATE: The platform has vastly broadened the range of COVID-19 analyses possible, and outputs from BCC19C analyses have been used to create dashboards, support routine reporting and contribute to the peer-reviewed literature. Published manuscripts (total of 15 as of July, 2023) have appeared in high-profile publications, generated significant media attention and informed policy and programming. In this paper, we conducted an analysis to identify sociodemographic and health characteristics associated with receiving SARS-CoV-2 laboratory testing, testing positive, and being fully vaccinated. Other published analyses have compared the relative clinical severity of different variants of concern; quantified the high "real-world" effectiveness of vaccines in addition to the higher risk of myocarditis among younger males following a 2nd dose of an mRNA vaccine; developed and validated an algorithm for identifying long-COVID patients in administrative data; identified a higher rate of diabetes and healthcare utilization among people with long-COVID; and measured the impact of the pandemic on mental health, among other analyses.

FUTURE PLANS: While the global COVID-19 health emergency has ended, our program of work remains robust. We plan to integrate additional datasets into the surveillance platform to further improve and expand covariate measurement and scope of analyses. Our analyses continue to focus on retrospective studies of various aspects of the COVID-19 pandemic, as well as prospective assessment of post-acute COVID-19 conditions and other impacts of the pandemic.}, } @article {pmid38449921, year = {2024}, author = {Demko, ZO and Yu, T and Mullapudi, SK and Varela Heslin, MG and Dorsey, CA and Payton, CB and Tornheim, JA and Blair, PW and Mehta, SH and Thomas, DL and Manabe, YC and Antar, AAR}, title = {Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6-12 Months Postinfection.}, journal = {Open forum infectious diseases}, volume = {11}, number = {3}, pages = {ofae027}, pmid = {38449921}, issn = {2328-8957}, support = {K23 AI135102/AI/NIAID NIH HHS/United States ; U54 EB007958/EB/NIBIB NIH HHS/United States ; }, abstract = {BACKGROUND: Few longitudinal studies available characterize long COVID outcomes out to 24 months, especially in people with nonsevere acute coronavirus disease 2019 (COVID-19). This study sought to prospectively characterize incidence and duration of long COVID symptoms and their association with quality of life (QoL) from 1-24 months after mild-to-moderate COVID-19 using validated tools in a diverse cohort of unvaccinated people infected with SARS-CoV-2 in 2020.

METHODS: At 1-3, 6, 12, 18, and 24 months post-COVID-19, 70 participants had orthostatic vital signs measured, provided blood, and completed surveys characterizing symptoms, QoL, and return to pre-COVID-19 health and activities using validated tools (FLU-PRO+, Fatigue Severity Scale, Insomnia Severity Index, General Practitioner Assessment of Cognition, Patient Health Questionnaire Depression 8-Item, Generalized Anxiety Disorder 7-Item, 36-Item Short-Form Health Survey, EuroQol EQ-5D-5L).

RESULTS: During the study period, 33% of participants experienced long COVID (had not returned to pre-COVID-19 health status and reported at least 1 symptom >90 days postinfection); 8% had not returned to their pre-COVID-19 health status 24 months postinfection. Long COVID symptoms peaked 6 months post-COVID-19, frequently causing activity limitations. Having long COVID was significantly associated with decreased QoL in multiple domains. Frequencies of orthostatic hypotension and tachycardia reflected levels reported in the general population. Within-person weight increased significantly between months 1 and 6. Long COVID was associated with pre-COVID-19 obesity and hyperlipidemia, but not with high-sensitivity C-reactive protein levels 1-3 months postinfection.

CONCLUSIONS: Long COVID occurs in a significant proportion of unvaccinated people, even if the acute illness was not severe. Long COVID prevalence peaked 6-12 months post-COVID-19, and a small proportion of participants still reported not returning to their pre-COVID-19 health status 24 months post-COVID-19.}, } @article {pmid38449917, year = {2024}, author = {Ramers, CB and Scott, JD and Struminger, BB}, title = {Burnout, Compassion Fatigue, and the Long Haul of Caring for Long COVID.}, journal = {Open forum infectious diseases}, volume = {11}, number = {3}, pages = {ofae080}, pmid = {38449917}, issn = {2328-8957}, abstract = {The current landscape of clinician burnout is prompting the need for our health care system to revise its approach toward complex conditions such as long coronavirus disease (COVID), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other postinfectious fatiguing illnesses (PIFIs). We discuss our efforts here at Family Health Center of San Diego (FHCSD) to help share insight and glean perspective from clinicians who have participated in our Centers for Disease Control and Prevention (CDC)-funded 3-year continuing professional development initiative. The Long COVID and Fatiguing Illness Recovery Program uses multidisciplinary team-based case consultation and peer-to-peer sharing of emerging best and promising practices (ie, teleECHO [Extension for Community Healthcare Outcomes]) to support the management of complex cases associated with long COVID, ME/CFS, and other PIFIs. We believe that this perspective captures a key moment in the trajectory of postpandemic clinician burnout and prompts further reflection and action from the health care system to improve clinician- and patient-level outcomes related to the care of patients with postinfectious fatiguing illnesses.}, } @article {pmid38449882, year = {2024}, author = {Katz, AA and Wainwright, S and Kelly, MP and Albert, P and Byrne, R}, title = {Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1354088}, pmid = {38449882}, issn = {2296-858X}, abstract = {BACKGROUND: The World Health Organization defines long COVID as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." Estimations of approximately 50 million individuals suffer from long COVID, reporting low health-related quality of life. Patients develop ongoing persistent symptoms that continue for more than 12 weeks that are not explained by another alternative diagnosis. To date, no current therapeutics are effective in treating the underlying pathophysiology of long COVID.

DISCUSSION: A comprehensive literature search using PubMed and Google Scholar was conducted and all available articles from November 2021 to January 2024 containing keywords long covid and hyperbaric oxygen were reviewed. These published studies, including case series and randomized trials, demonstrate that utilizing Hyperbaric Oxygen Therapy (HBO) provided significant improvement in patients with long COVID.

CONCLUSION: A large cohort of patients suffer from long COVID or post-COVID-19 syndrome after recovery from their acute infection with no effective treatment options. HBO is a safe treatment and may provide benefit for this population and should continue to be researched for adjunctive treatment of long COVID.}, } @article {pmid38448808, year = {2024}, author = {Ruan, W and Xu, J and Yang, F and Wu, X and Ying, K}, title = {Tropheryma whipplei infection in the lung of a patient with long COVID: a case report.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {292}, pmid = {38448808}, issn = {1471-2334}, support = {Y202351581//the Scientific Research Fund of the Zhejiang Provincial Education Department/ ; Y202351581//the Scientific Research Fund of the Zhejiang Provincial Education Department/ ; Y202351581//the Scientific Research Fund of the Zhejiang Provincial Education Department/ ; Y202351581//the Scientific Research Fund of the Zhejiang Provincial Education Department/ ; Y202351581//the Scientific Research Fund of the Zhejiang Provincial Education Department/ ; LY17H160007//the Zhejiang Provincial Natural Science Foundation of China/ ; LY17H160007//the Zhejiang Provincial Natural Science Foundation of China/ ; LY17H160007//the Zhejiang Provincial Natural Science Foundation of China/ ; LY17H160007//the Zhejiang Provincial Natural Science Foundation of China/ ; LY17H160007//the Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Male ; Humans ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Tropheryma ; *COVID-19/complications/diagnosis ; Dyspnea ; *Actinomycetales Infections ; Lung/diagnostic imaging ; }, abstract = {BACKGROUND: Immune dysregulation in individuals with long COVID has been detected. Differential diagnosis of diffuse infiltration on chest CT in long COVID is challenging.

CASE PRESENTATION: A 62-year-old man presented with a 10-month history of dyspnea after COVID-19 infection. Dyspnea became worse in the one month preceding presentation. The chest CT showed multifocal, subpleural, bilateral opacities due to long-COVID, and infiltration around the bronchovascular bundle in the bilateral lower lung field. The pathology for the transbronchial cryobiopsy (TBCB) first reported chronic inflammation (mainly interstitial pneumonia). The patient had positive results on tests for the antibody, RO-52+, EJ+. The presumptive diagnosis of connective tissue disease-interstitial lung disease was made. Prednisone and cyclophosphamide were given. At follow-up one month later, the chest CT showed new diffuse ground-glass infiltration. The previous TBCB specimen was re-evaluated. Foamy macrophages were found in the alveolar air space. Periodic acid-Schiff (PAS) staining was performed. Numerous intracytoplasmic organisms were detected, with morphologic features consistent with those of Tropheryma whipplei. The patient recovered after intravenous ceftriaxone and oral trimethoprim-sulfamethoxazole. The final diagnosis was lung T. whipplei infection and long COVID-19.

CONCLUSION: This is the first case report of Tropheryma whipplei infection in the lung of a patient with long COVID-19. T. whipplei should be considered as a potential pathogen for diffuse lung infiltration in the post-COVID-19 era.}, } @article {pmid38448223, year = {2024}, author = {Sehmbi, T and Wearden, A and Peters, S and Dienes, K}, title = {'The world was going through what we go through everyday': The experiences of women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) living with their partners during the COVID-19 lockdown in the United Kingdom.}, journal = {British journal of health psychology}, volume = {29}, number = {3}, pages = {629-643}, doi = {10.1111/bjhp.12717}, pmid = {38448223}, issn = {2044-8287}, mesh = {Humans ; *COVID-19/psychology ; Female ; *Fatigue Syndrome, Chronic/psychology ; United Kingdom ; Adult ; *Qualitative Research ; Middle Aged ; SARS-CoV-2 ; Quarantine/psychology ; Fear/psychology ; Male ; }, abstract = {OBJECTIVES: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term debilitating illness characterised by profound and persistent fatigue (JAMA: The Journal of the American Medical Association, 313, 2015, 1101). The current study aims to explore the experiences of women with ME/CFS living with their partners during the COVID-19 pandemic in the United Kingdom.

DESIGN: The study adopted a qualitative design comprising semi-structured interviews with participants. Interviews were analysed using thematic analysis (TA).

METHODS: Participants were women with ME/CFS (n = 21) recruited through ME/CFS support groups in the United Kingdom. All participants were in romantic relationships and lived with their partners.

RESULTS: Data were organised into three themes: (1) lockdown disrupting routine, (2) reducing difference and (3) fear of getting COVID-19. People with ME/CFS found that lockdown disrupted their well-established routines. Although routines were disrupted by partners and increased working-from-home practices, participants found having partners at home helpful. People with ME/CFS believed that the changes induced by the pandemic reduced the differences between themselves and the outside world which, prior to lockdown, had felt prominent. They were fearful of getting COVID-19 as they believed this would make their ME/CFS worse. This meant that for people with ME/CFS, the lifting of the lockdown restrictions was an anxiety-provoking time, hence impacting symptoms. People with ME/CFS continued to adhere to government guidelines after national restrictions were eased.

CONCLUSIONS: This study outlines the experiences of women with ME/CFS during COVID-19, alongside the long-term impact this has had due to the changes that the pandemic imposed. These findings may have implications for those with long COVID.}, } @article {pmid38447388, year = {2024}, author = {van der Feltz-Cornelis, C and Turk, F and Sweetman, J and Khunti, K and Gabbay, M and Shepherd, J and Montgomery, H and Strain, WD and Lip, GYH and Wootton, D and Watkins, CL and Cuthbertson, DJ and Williams, N and Banerjee, A}, title = {Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis.}, journal = {General hospital psychiatry}, volume = {88}, number = {}, pages = {10-22}, doi = {10.1016/j.genhosppsych.2024.02.009}, pmid = {38447388}, issn = {1873-7714}, mesh = {Humans ; *COVID-19/epidemiology ; Prevalence ; *Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/epidemiology/etiology ; Mental Disorders/epidemiology ; }, abstract = {OBJECTIVE: Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions.

METHODS: Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection.

FINDINGS: 17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24 months), the combined prevalence of mental health conditions and brain fog was 20·4% (95% CI 11·1%-34·4%), being lower among those previously hospitalised than in community-managed patients(19·5 vs 29·7% respectively; p = 0·047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p = ·000).

CONCLUSIONS: Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.}, } @article {pmid38446228, year = {2024}, author = {Delogu, AB and Aliberti, C and Birritella, L and De Rosa, G and De Rose, C and Morello, R and Cambise, N and Marino, AG and Belmusto, A and Tinti, L and Di Renzo, A and Lanza, GA and Buonsenso, D}, title = {Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.}, journal = {European journal of pediatrics}, volume = {183}, number = {5}, pages = {2375-2382}, pmid = {38446228}, issn = {1432-1076}, support = {65925795//Pfizer/ ; }, mesh = {Humans ; Male ; Female ; Child ; Case-Control Studies ; *COVID-19/physiopathology/complications ; Adolescent ; *Heart Rate/physiology ; *Autonomic Nervous System/physiopathology ; *Electrocardiography, Ambulatory ; Post-Acute COVID-19 Syndrome ; Heart/physiopathology ; Electrocardiography ; Echocardiography ; SARS-CoV-2 ; }, abstract = {Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography. Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.}, } @article {pmid38444907, year = {2024}, author = {Cho, SM and Premraj, L and Battaglini, D and Fanning, JP and Suen, J and Bassi, GL and Fraser, J and Robba, C and Griffee, M and Solomon, T and Semple, MG and Baillie, K and Sigfrid, L and Scott, JT and Citarella, BW and Merson, L and Arora, RC and Whitman, G and Thomson, D and White, N and , }, title = {Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after coronavirus disease 2019 hospitalization: an international multi-centre prospective observational study.}, journal = {Brain communications}, volume = {6}, number = {2}, pages = {fcae036}, pmid = {38444907}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; K23 HL157610/HL/NHLBI NIH HHS/United States ; MR/S032304/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Although it is known that coronavirus disease 2019 can present with a range of neurological manifestations and in-hospital complications, sparse data exist on whether these initial neurological symptoms of coronavirus disease 2019 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; PANSC) and whether female versus male sex impacts symptom resolution. In this international, multi-centre, prospective, observational study across 407 sites from 15 countries (30 January 2020 to 30 April 2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time. PANSC symptoms included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia and muscle ache/joint pain, on which information was collected at index hospitalization and during follow-up assessments. The analysis considered a time to the resolution of individual and all neurological symptoms. The resulting times were modelled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. The model results were summarized as cumulative probability functions and age-adjusted and sex-adjusted median times to resolution. We included 6862 hospitalized adults with coronavirus disease 2019, who had follow-up assessments. The median age of the participants was 57 years (39.2% females). Males and females had similar baseline characteristics, except that more males (versus females) were admitted to the intensive care unit (30.5 versus 20.3%) and received mechanical ventilation (17.2 versus 11.8%). Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median = 102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. The reported prevalence in females was generally higher (versus males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, although fatigue, altered consciousness and myalgia remained unresolved in >10% of the cohort. Females had a longer time to the resolution (5.2 versus 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom. In the multivariable analysis, males were associated with a shorter time to the resolution of symptoms (hazard ratio = 1.53; 95% confidence interval = 1.39-1.69). Intensive care unit admission was associated with a longer time to the resolution of symptoms (hazard ratio = 0.68; 95% confidence interval = 0.60-0.77). Post-discharge stroke was uncommon (0.3% in females and 0.5% in males). Despite the methodological challenges involved in the collection of survey data, this international multi-centre prospective cohort study demonstrated that PANSC following index hospitalization was high. Symptom prevalence was higher and took longer to resolve in females than in males. This supported the fact that while males were sicker during acute illness, females were disproportionately affected by PANSC.}, } @article {pmid38444741, year = {2024}, author = {Verma, A and Manojkumar, A and Dhasmana, A and Tripathi, MK and Jaggi, M and Chauhan, SC and Chauhan, DS and Yallapu, MM}, title = {Recurring SARS-CoV-2 variants: an update on post-pandemic, co-infections and immune response.}, journal = {Nanotheranostics}, volume = {8}, number = {2}, pages = {247-269}, pmid = {38444741}, issn = {2206-7418}, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Coinfection ; Pandemics ; Protein Subunit Vaccines ; }, abstract = {The post-pandemic era following the global spread of the SARS-CoV-2 virus has brought about persistent concerns regarding recurring coinfections. While significant strides in genome mapping, diagnostics, and vaccine development have controlled the pandemic and reduced fatalities, ongoing virus mutations necessitate a deeper exploration of the interplay between SARS-CoV-2 mutations and the host's immune response. Various vaccines, including RNA-based ones like Pfizer and Moderna, viral vector vaccines like Johnson & Johnson and AstraZeneca, and protein subunit vaccines like Novavax, have played critical roles in mitigating the impact of COVID-19. Understanding their strengths and limitations is crucial for tailoring future vaccines to specific variants and individual needs. The intricate relationship between SARS-CoV-2 mutations and the immune response remains a focus of intense research, providing insights into personalized treatment strategies and long-term effects like long-COVID. This article offers an overview of the post-pandemic landscape, highlighting emerging variants, summarizing vaccine platforms, and delving into immunological responses and the phenomenon of long-COVID. By presenting clinical findings, it aims to contribute to the ongoing understanding of COVID-19's progression in the aftermath of the pandemic.}, } @article {pmid38444417, year = {2024}, author = {Bonnet, U and Juckel, G and Kuhn, J}, title = {Antidepressants for prevention of severe COVID-19, Long COVID and outlook for other viral diseases.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1305184}, pmid = {38444417}, issn = {2296-858X}, } @article {pmid38443459, year = {2024}, author = {Nakano, Y and Sunada, N and Tokumasu, K and Honda, H and Otsuka, Y and Sakurada, Y and Matsuda, Y and Hasegawa, T and Omura, D and Ochi, K and Yasuda, M and Hagiya, H and Ueda, K and Otsuka, F}, title = {Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {5446}, pmid = {38443459}, issn = {2045-2322}, mesh = {Aged ; Humans ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19/diagnosis ; *Endocrine System Diseases/diagnosis/epidemiology ; Outpatients ; *Metabolic Diseases ; }, abstract = {Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.}, } @article {pmid38443223, year = {2024}, author = {Annesley, SJ and Missailidis, D and Heng, B and Josev, EK and Armstrong, CW}, title = {Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies.}, journal = {Trends in molecular medicine}, volume = {30}, number = {5}, pages = {443-458}, doi = {10.1016/j.molmed.2024.02.003}, pmid = {38443223}, issn = {1471-499X}, mesh = {Humans ; *COVID-19/complications/virology ; *Fatigue Syndrome, Chronic/virology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed 'long COVID' (LC). Both ME/CFS and LC share many clinical similarities. Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests. Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.}, } @article {pmid38442116, year = {2024}, author = {Cruickshank, M and Brazzelli, M and Manson, P and Torrance, N and Grant, A}, title = {What is the impact of long-term COVID-19 on workers in healthcare settings? A rapid systematic review of current evidence.}, journal = {PloS one}, volume = {19}, number = {3}, pages = {e0299743}, pmid = {38442116}, issn = {1932-6203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Health Facilities ; Health Resources ; Health Personnel ; Chronic Disease ; Dyspnea ; }, abstract = {BACKGROUND: Long COVID is a devastating, long-term, debilitating illness which disproportionately affects healthcare workers, due to the nature of their work. There is currently limited evidence specific to healthcare workers about the experience of living with Long COVID, or its prevalence, pattern of recovery or impact on healthcare.

OBJECTIVE: Our objective was to assess the effects of Long COVID among healthcare workers and its impact on health status, working lives, personal circumstances, and use of health service resources.

METHODS: We conducted a systematic rapid review according to current methodological standards and reported it in adherence to the PRISMA 2020 and ENTREQ statements.

RESULTS: We searched relevant electronic databases and identified 3770 articles of which two studies providing qualitative evidence and 28 survey studies providing quantitative evidence were eligible. Thematic analysis of the two qualitative studies identified five themes: uncertainty about symptoms, difficulty accessing services, importance of being listened to and supported, patient versus professional identity and suggestions to improve communication and services for people with Long COVID. Common long-term symptoms in the survey studies included fatigue, headache, loss of taste and/or smell, breathlessness, dyspnoea, difficulty concentrating, depression and anxiety.

CONCLUSION: Healthcare workers struggled with their dual identity (patient/doctor) and felt dismissed or not taken seriously by their doctors. Our findings are in line with those in the literature showing that there are barriers to healthcare professionals accessing healthcare and highlighting the challenges of receiving care due to their professional role. A more representative approach in Long COVID research is needed to reflect the diverse nature of healthcare staff and their occupations. This rapid review was conducted using robust methods with the codicil that the pace of research into Long COVID may mean relevant evidence was not identified.}, } @article {pmid38441885, year = {2024}, author = {Adu-Amankwaah, J}, title = {Behind the shadows: Bringing the cardiovascular secrets of long COVID into light.}, journal = {European journal of preventive cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjpc/zwae098}, pmid = {38441885}, issn = {2047-4881}, } @article {pmid38439631, year = {2025}, author = {Polascik, BW and Karklins, SP and Johnson, MC and Hammert, WC and McMichael, AJ}, title = {Acquired Aquagenic Syringeal Keratoderma Following COVID-19 Infection.}, journal = {Hand (New York, N.Y.)}, volume = {20}, number = {1}, pages = {NP12-NP19}, pmid = {38439631}, issn = {1558-9455}, mesh = {Humans ; Male ; *COVID-19/complications ; Young Adult ; *Keratoderma, Palmoplantar/etiology ; *Water/adverse effects ; SARS-CoV-2 ; }, abstract = {Aquagenic syringeal keratoderma (ASK), rare in males, is characterized by the rapid onset of edematous palmar wrinkling with small white papules after brief contact with water or sweat. A 24-year-old atopic male presented with a 2-week subacute history of bilateral palmar edema with whitish-colored papules after exposure to water, 3 months after having had COVID-19 infection treated with a full course of ritonavir-boosted nirmatrelvir (PAXLOVID[TM]). He had received 3 COVID-19 vaccines (Pfizer, New York, NY) about 12 months prior. Workup was negative. Initial spontaneous near-resolution 2 months after onset was temporary, with recurrence 1 month later. Treatment with 12% topical aluminum chloride was ineffective. Botulinum toxin injection to both palms led to resolution of symptoms that has been sustained for 7 months. The association between atopy and ASK remains weak. We present a case of new-onset ASK in an adult male 3 months following COVID-19 infection without a history of excessive handwashing. Our patient may have had a predisposition to recurrent ASK due to his history of atopy including atopic dermatitis and food allergy anaphylaxis combined with prior COVID-19 infection. It is possible that ASK is a novel manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) infection or long COVID.}, } @article {pmid38435484, year = {2024}, author = {Okada, M and Ishida, N and Kanzaki, S and Kawada, I and Nagashima, K and Terai, H and Hiruma, G and Namkoong, H and Asakura, T and Masaki, K and Ohgino, K and Miyata, J and Chubachi, S and Kodama, N and Maeda, S and Sakamoto, S and Okamoto, M and Nagasaki, Y and Umeda, A and Miyagawa, K and Shimada, H and Minami, K and Hagiwara, R and Ishii, M and Sato, Y and Fukunaga, K}, title = {Upper Respiratory Symptoms as Long COVID: Insight from a Multicenter Cohort Study.}, journal = {OTO open}, volume = {8}, number = {1}, pages = {e120}, pmid = {38435484}, issn = {2473-974X}, abstract = {OBJECTIVE: This study aimed to investigate the clinical features of long COVID cases presenting with upper respiratory symptoms, a topic not yet fully elucidated.

STUDY DESIGN: Prospective cohort study.

SETTING: A multicenter study involving 26 medical facilities in Japan.

METHODS: Inclusion criteria were patients aged ≥18 years old with a confirmed COVID-19 diagnosis via severe acute respiratory syndrome coronavirus 2 polymerase chain reaction or antigen testing, who were hospitalized at the participating medical facilities. Analyzing clinical information and patient-reported outcomes from 1009 patients were analyzed. The outcome measured the degree of initial symptoms for taste or olfactory disorders and assessed the likelihood of these symptoms persisting as long COVID, as well as the impact on quality of life if the upper respiratory symptoms persisted as long COVID.

RESULTS: Patients with high albumin, low C-reactive protein, and low lactate dehydrogenase in laboratory tests tended to experience taste or olfactory disorders as part of long COVID. Those with severe initial symptoms had a higher risk of experiencing residual symptoms at 3 months, with an odds ratio of 2.933 (95% confidence interval [CI], 1.282-6.526) for taste disorders and 3.534 (95% CI, 1.382-9.009) for olfactory disorders. Presence of upper respiratory symptoms consistently resulted in lower quality of life scores.

CONCLUSION: The findings from this cohort study suggest that severe taste or olfactory disorders as early COVID-19 symptoms correlate with an increased likelihood of persistent symptoms in those disorders as long COVID.}, } @article {pmid38433036, year = {2024}, author = {Williams, GP and Yu, ED and Shapiro, K and Wang, E and Freuchet, A and Frazier, A and Lindestam Arlehamn, CS and Sette, A and da Silva Antunes, R}, title = {Investigating viral and autoimmune T cell responses associated with post-acute sequelae of COVID-19.}, journal = {Human immunology}, volume = {85}, number = {3}, pages = {110770}, pmid = {38433036}, issn = {1879-1166}, support = {U19 AI118626/AI/NIAID NIH HHS/United States ; U19 AI142742/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Male ; Middle Aged ; *CD8-Positive T-Lymphocytes/immunology ; Female ; *CD4-Positive T-Lymphocytes/immunology ; *Post-Acute COVID-19 Syndrome ; Adult ; Aged ; Autoimmunity/immunology ; Cytokines/metabolism/immunology ; Autoantigens/immunology ; }, abstract = {Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as 'brain fog,' posing concern for their debilitating nature and potential role in other neurological disorders. However, the underlying potential pathogenic mechanisms of the neurological complications of PASC is largely unknown. Herein, we investigated differences in antigen-specific T cell responses from the peripheral blood towards SARS-CoV-2, latent viruses, or neuronal antigens in 14 PASC individuals with neurological manifestations (PASC-N) versus 22 individuals fully recovered from COVID-19. We employed Activation Induced Marker (AIM), ICS and FluoroSpot assays to determine the specificity and magnitude of CD4[+] and CD8[+] T cell responses towards SARS-CoV-2 (Spike and rest of proteome), latent viruses (CMV, EBV), and several neuronal antigens. Overall, we observed similar antigen-specific T cell frequencies and cytokine effector T cell responses between PASC donors compared to recovered controls for all antigens tested (viral or autoantigen) in both CD4[+] and CD8[+] T cell compartments. Our findings suggest that PASC-N does not appear to be associated with changes in antigen-specific T cell responses towards a subset of disease-relevant targets, but more studies in a larger cohort are needed to confirm these unaltered responses.}, } @article {pmid38432691, year = {2024}, author = {Ordaya, EE and Razonable, RR}, title = {Emerging anti-spike monoclonal antibodies against SARS-CoV-2.}, journal = {Expert opinion on biological therapy}, volume = {24}, number = {3}, pages = {191-201}, doi = {10.1080/14712598.2024.2326647}, pmid = {38432691}, issn = {1744-7682}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; }, abstract = {INTRODUCTION: Anti-spike monoclonal antibodies (mAbs) were previously authorized for the prevention and treatment of COVID-19 in immunocompromised patients. However, they are no longer authorized in the U.S. due to their lack of neutralizing activity against current circulating SARS-CoV-2 Omicron variants.

AREAS COVERED: We summarized the available data on emergent mAbs in the early stages of clinical development. Consistent with data on prior mAbs, these novel agents have been well tolerated and demonstrated a good safety profile in early clinical trials. Additionally, many of them have been engineered to ensure prolonged half-life and combined with other mAbs to overcome the potential for emerging resistant mutants. Interestingly, one of these agents has been evaluated using an inhaled route of administration, and another agent is being evaluated for treatment of long COVID.

EXPERT OPINION: Although the available data of novel mAbs holds promise, we anticipate that these agents will face similar challenges encountered by prior authorized agents, including the continued evolution of SARS-CoV-2 and emergence of new escape mutations. Strategies to potentially mitigate this are discussed. Based on prior successful experience, immunocompromised patients will certainly benefit from the utilization of mAbs for the prevention and treatment of COVID-19; thus, we need to design potential interventions to ensure the sustained activity of these agents.}, } @article {pmid38432584, year = {2024}, author = {Powell, AA and Dowell, AC and Moss, P and Ladhani, SN and , }, title = {Current state of COVID-19 in children: 4 years on.}, journal = {The Journal of infection}, volume = {88}, number = {5}, pages = {106134}, doi = {10.1016/j.jinf.2024.106134}, pmid = {38432584}, issn = {1532-2742}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control/*complications ; Child ; *SARS-CoV-2 ; *COVID-19 Vaccines/administration & dosage ; United Kingdom/epidemiology ; Systemic Inflammatory Response Syndrome/epidemiology ; Child, Preschool ; Vaccination ; Adolescent ; }, abstract = {Children have been disproportionately affected by the COVID-19 pandemic. Despite evidence of a very low risk of severe disease, children were subjected to extensive lockdown, restriction and mitigation measures, including school closures, to control the rapid spread of SARS-CoV-2 in most parts of the world. In this review we summarise the UK experience of COVID-19 in children four years into the largest and longest pandemic of this century. We address the risks of SARS-CoV-2 infection, immunity, transmission, severity and outcomes in children. We also assess the implementation, uptake, effectiveness and impact of COVID-19 vaccination, as well as the emergence, evolution and near disappearance of PIMS-TS (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) and current understanding of long COVID in children. This review consolidates current knowledge on childhood COVID-19 and emphasises the importance of continued research and the need for research-driven public health actions and policy decisions, especially in the context of new variants and future vaccines.}, } @article {pmid38432061, year = {2024}, author = {Fernández-de-Las-Peñas, C and Arias-Navalón, JA and Martín-Guerrero, JD and Pellicer-Valero, OJ and Cigarán-Méndez, M}, title = {Trajectory of anxiety/depressive symptoms and sleep quality in individuals who had been hospitalized by COVID-19: The LONG-COVID-EXP multicenter study.}, journal = {Journal of psychosomatic research}, volume = {179}, number = {}, pages = {111635}, doi = {10.1016/j.jpsychores.2024.111635}, pmid = {38432061}, issn = {1879-1360}, mesh = {Humans ; Depression/epidemiology/diagnosis ; *COVID-19/epidemiology ; Sleep Quality ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Anxiety/epidemiology/diagnosis ; *Sleep Initiation and Maintenance Disorders/epidemiology ; }, abstract = {OBJECTIVE: To apply Sankey plots and exponential bar plots for visualizing the evolution of anxiety/depressive symptoms and poor sleep in previously hospitalized COVID-19 survivors.

METHODS: A sample of 1266 subjects who were hospitalized due to a SARS-CoV-2 from March-May 2020 were assessed at 8.4 (T1), 13.2 (T2) and 18.3 (T3) months after hospitalization. The Hospital Anxiety and Depression Scale was used to determine anxiety (HADS-A) and depressive (HADS-D) symptoms. The Pittsburgh Sleep Quality Index (PSQI) evaluated sleep quality. Clinical features, onset symptoms and hospital data were collected from medical records.

RESULTS: Sankey plots revealed that the prevalence of anxiety symptomatology (HADS-A ≥ 8 points) was 22.5% (n = 285) at T1, 17.6% (n = 223) at T2, and 7.9% (n = 100) at T3, whereas the prevalence of depressive symptoms (HADS-D ≥ 8 points) was 14.6% (n = 185) at T1, 10.9% (n = 138) at T2, and 6.1% (n = 78) at T3. Finally, the prevalence of poor sleep (PSQI≥8 points) decreased from 32.8% (n = 415) at T1, to 28.8% (n = 365) at T2, and to 24.8% (n = 314) at T3. The recovery curves show a decrease trend visualizing that these symptoms recovered the following years after discharge. The regression models did not reveal medical records associated with anxiety/depressive symptoms or poor sleep.

CONCLUSION: The use of Sankey plots shows a fluctuating evolution of anxiety/depressive symptoms and poor sleep during the first years after the infection. In addition, exponential bar plots revealed a decrease prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.}, } @article {pmid38431959, year = {2024}, author = {Kusuma, IY and Suherman, S}, title = {The Pulse of Long COVID on Twitter: A Social Network Analysis.}, journal = {Archives of Iranian medicine}, volume = {27}, number = {1}, pages = {36-43}, pmid = {38431959}, issn = {1735-3947}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Social Media ; Social Network Analysis ; *COVID-19 ; Heart Rate ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID) is a complex and multifaceted health condition with a range of severe symptoms that can last for weeks or even months after the acute phase of the illness has passed. Employing social network analysis (SNA) can rapidly provide significant health information to communities related to long COVID. This study aimed to identify the key themes, most influential users, and overall sentiments in the Twitter discourse on long COVID.

METHODS: Data were collected from a Twitter search with the specific keywords "long COVID" from December 1, 2022, to February 22, 2023, using NodeXL Pro. Visualizations, including network graphs and key influencers, were created using Gephi, and sentiment analysis was conducted with Azure Machine.

RESULTS: In total, 119,185 tweets from 94325 users were related to long COVID. Top influencers include medical professionals, researchers, journalists, and public figures, with news media platforms as primary information sources; the most common hashtag was #longCOVID, indicating that it is a significant issue of concern among the Twitter community. In the sentiment analysis, most tweets were negative.

CONCLUSION: The study highlights the importance of critically evaluating information shared by influential users and seeking out multiple sources of information when making health-related decisions. In addition, it emphasizes the value of examining social media conversations to understand public discourse on long COVID and suggests that future researchers could explore the role of social media in shaping public perceptions and behaviors related to health issues. Strategies for enhancing scientific journal engagement and influence in online discussions are discussed as well.}, } @article {pmid38429459, year = {2024}, author = {Marques, O and Muckenthaler, MU}, title = {Alterations of iron homeostasis as a potential druggable driver of long COVID.}, journal = {Nature immunology}, volume = {25}, number = {3}, pages = {387-389}, pmid = {38429459}, issn = {1529-2916}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Iron ; Homeostasis ; }, } @article {pmid38428523, year = {2024}, author = {Banerjee, A}, title = {Disparities by Social Determinants of Health: Links Between Long COVID and Cardiovascular Disease.}, journal = {The Canadian journal of cardiology}, volume = {40}, number = {6}, pages = {1123-1134}, doi = {10.1016/j.cjca.2024.02.017}, pmid = {38428523}, issn = {1916-7075}, mesh = {Humans ; *Social Determinants of Health ; *COVID-19/epidemiology ; *Cardiovascular Diseases/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Healthcare Disparities ; Socioeconomic Factors ; Health Status Disparities ; SARS-CoV-2 ; }, abstract = {Long COVID has been defined by the World Health Organisation as "continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." Cardiovascular disease is implicated as a risk factor, concomitant condition, and consequence of long COVID. As well as heterogeneity in definition, presentation, and likely underlying pathophysiology of long COVID, disparities by social determinants of health, extensively studied and described in cardiovascular disease, have been observed in 3 ways. First, underlying long-term conditions, such as cardiovascular disease and its risk factors, are associated with incidence and severity of long COVID, and previously described socioeconomic disparities in these factors are important in exacerbating disparities in long COVID. Second, socioeconomic disparities in management of COVID-19 may themselves lead to distal disparities in long COVID. Third, there are socioeconomic disparities in the way that long COVID is diagnosed, managed, and prevented. Together, factors such as age, sex, deprivation, and ethnicity have far-reaching implications in this new postviral syndrome across its management spectrum. There are similarities and differences compared with disparities for cardiovascular disease. Some of these disparities are in fact, inequalities, that is, rather than simply observed variations, they represent injustices with costs to individuals, communities, and economies. This review of current literature considers opportunities to prevent or at least attenuate these socioeconomic disparities in long COVID and cardiovascular disease, with special challenges for research, clinical practice, public health, and policy in a new disease which is evolving.}, } @article {pmid38428480, year = {2024}, author = {Bouwmans, P and Malahe, SRK and Messchendorp, AL and Vart, P and Imhof, C and Sanders, JF and Gansevoort, RT and de Vries, APJ and Abrahams, AC and Bemelman, FJ and Vervoort, JPM and Hilbrands, LB and Ten Dam, MAGJ and van den Dorpel, RMA and Rispens, T and Steenhuis, M and Reinders, MEJ and Hemmelder, MH and , }, title = {Post COVID-19 condition imposes significant burden in patients with advanced chronic kidney disease: A nested case-control study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {142}, number = {}, pages = {106990}, doi = {10.1016/j.ijid.2024.106990}, pmid = {38428480}, issn = {1878-3511}, mesh = {Humans ; Case-Control Studies ; COVID-19 Vaccines ; Prospective Studies ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Renal Insufficiency, Chronic/complications/epidemiology/therapy ; Chronic Disease ; }, abstract = {BACKGROUND: The burden of post COVID-19 condition (PCC) is not well studied in patients with advanced kidney disease.

METHODS: A large prospective cohort of SARS-CoV-2 vaccinated patients with chronic kidney disease stages G4-G5 (CKD G4/5), on dialysis, and kidney transplant recipients (KTR) were included. Antibody levels were determined after vaccination. Presence of long-lasting symptoms was assessed in patients with and without prior COVID-19 and compared using logistic regression. In patients with prior COVID-19, PCC was defined according to the WHO definition.

RESULTS: Two hundred sixteen CKD G4/5 patients, 375 dialysis patients, and 2005 KTR were included. Long-lasting symptoms were reported in 204/853 (24%) patients with prior COVID-19 and in 297/1743 (17%) patients without prior COVID-19 (aOR: 1.45 (1.17-1.78)], P < 0.001). PCC was prevalent in 29% of CKD G4/5 patients, 21% of dialysis patients, and 24% of KTR. In addition, 69% of patients with PCC reported (very) high symptom burden. Odds of PCC was lower per 10-fold increase in antibody level after vaccination (aOR 0.82 [0.70-0.96], P = 0.01) and higher in case of COVID-19 related hospital admission (aOR 4.64 [2.61-8.25], P = 0.003).

CONCLUSIONS: CKD G4/5 patients, dialysis patients, and KTR are at risk for PCC with high symptom burden after SARS-CoV-2 vaccination, especially if antibody levels are low and in case of hospitalization due to COVID-19.}, } @article {pmid38425701, year = {2024}, author = {Leonel, JW and Ciurleo, GCV and Formiga, AM and Vasconcelos, TMF and de Andrade, MH and Feitosa, WLQ and Sobreira-Neto, AA and Portugal, CG and Morais, LM and Marinho, SC and Gomes, EABM and Feitosa, EAAF and Sobreira, EST and Oriá, RB and Sobreira-Neto, MA and Braga-Neto, P}, title = {Long COVID: neurological manifestations - an updated narrative review.}, journal = {Dementia & neuropsychologia}, volume = {18}, number = {}, pages = {e20230076}, pmid = {38425701}, issn = {1980-5764}, abstract = {Infection with the SARS-CoV-2 virus can lead to neurological symptoms in the acute phase and in the Long COVID phase. These symptoms usually involve cognition, sleep, smell disorders, psychiatric manifestations, headache and others. This condition is more commonly described in young adults and women. This symptomatology can follow severe or mild cases of the disease. The importance of this issue resides in the high prevalence of neurological symptoms in the Long COVID phase, which entails significant morbidity in this population. In addition, such a condition is associated with high health care costs, with some estimates hovering around 3.7 trillion US dollars. In this review, we will sequentially describe the current knowledge about the most prevalent neurological symptoms in Long COVID, as well as their pathophysiology and possible biomarkers.}, } @article {pmid38424537, year = {2024}, author = {Kwan, ATH and Le, GH and Guo, Z and Ceban, F and Teopiz, KM and Rhee, TG and Ho, R and Di Vincenzo, JD and Badulescu, S and Meshkat, S and Cao, B and Rosenblat, JD and Dev, DA and Phan, L and Subramaniapillai, M and McIntyre, RS}, title = {Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine.}, journal = {Annals of general psychiatry}, volume = {23}, number = {1}, pages = {10}, pmid = {38424537}, issn = {1744-859X}, abstract = {BACKGROUND: Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI.

METHODS: This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint.

RESULTS: Our findings showed significant effects for time (χ[2] = 7.771, p = 0.005), treatment (χ[2] = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ[2] = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047).

CONCLUSION: Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo.

TRIAL REGISTRATION: NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).}, } @article {pmid38424312, year = {2024}, author = {Queiroz, MAF and Brito, WRDS and Pereira, KAS and Pereira, LMS and Amoras, EDSG and Lima, SS and Santos, EFD and Costa, FPD and Sarges, KML and Cantanhede, MHD and Brito, MTFM and Silva, ALSD and Leite, MM and Viana, MNDSA and Rodrigues, FBB and Silva, RD and Viana, GMR and Chaves, TDSS and Veríssimo, AOL and Carvalho, MDS and Henriques, DF and Silva, CPD and Nunes, JAL and Costa, IB and Cayres-Vallinoto, IMV and Brasil-Costa, I and Quaresma, JAS and Falcão, LFM and Santos, EJMD and Vallinoto, ACR}, title = {Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4974}, pmid = {38424312}, issn = {2045-2322}, support = {n° 304835/2022-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; n° 401235/2020-3; n° 302935/2021-5; INCT-VER nº 406360/2022-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 09/2021//Secretariat of Science, Technology and Higher, Professional and Technological Education/ ; n° 005/2020//Fundação Amazônia de Amparo a Estudos e Pesquisa do Pará/ ; PAPQ/2023//Federal University of Para/ ; }, mesh = {Humans ; *COVID-19 ; Interferon-alpha ; Interleukin-6 ; Nucleotidyltransferases/genetics/metabolism ; *Post-Acute COVID-19 Syndrome ; Signal Transduction/genetics ; Tumor Necrosis Factor-alpha/genetics ; }, abstract = {The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.}, } @article {pmid38424126, year = {2024}, author = {Stepanova, N and Driianska, V and Rysyev, A and Ostapenko, T and Kalinina, N}, title = {IL-6 and IL-17 as potential links between pre-existing hypertension and long-term COVID sequelae in patients undergoing hemodialysis: a multicenter cross-sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4968}, pmid = {38424126}, issn = {2045-2322}, mesh = {Humans ; Blood Pressure ; *COVID-19/complications ; Cross-Sectional Studies ; *Hypertension/epidemiology ; Interleukin-17 ; Interleukin-6 ; Post-Acute COVID-19 Syndrome ; Renal Dialysis/adverse effects ; }, abstract = {Long COVID, characterized by persistent symptoms following acute infection, poses a significant health challenge, particularly for patients with pre-existing chronic conditions such as hypertension. We hypothesized that an increase in the production of interleukins (IL)-6 and IL-17 could serve as a potential mechanism linking pre-existing uncontrolled blood pressure (BP) to the occurrence of long-term COVID sequelae in patients undergoing hemodialysis (HD). This cross-sectional study examined serum IL-6 and IL-17 levels in 80 patients undergoing HD, considering preinfection BP, the presence of long-term COVID sequelae, and the time interval after acute COVID-19 infection, which was either 5 or 10 months. Controlled BP was defined as a 3-month average pre-dialysis BP < 140/90 mmHg and post-dialysis < 130/80 mmHg. The findings suggest that the prevalence of long-term COVID sequelae was significantly higher in patients with uncontrolled BP than in the BP-controlled group. Both IL-6 and IL-17 concentrations were also significantly higher in patients with uncontrolled BP compared with the BP-controlled group. The patients with long-term COVID sequelae had higher IL-6 and IL-17 values than the fully recovered patients at both time points, but their concentrations decreased significantly over time. Further research and prospective studies are warranted to validate these findings.}, } @article {pmid38424104, year = {2024}, author = {Song, M and Liu, X and Shen, W and Wang, Z and Wu, J and Jiang, J and Liu, Y and Xu, T and Bian, T and Zhang, M and Sun, W and Huang, M and Ji, N}, title = {IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3β signaling pathway.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {5038}, pmid = {38424104}, issn = {2045-2322}, support = {BE2020616//Jiangsu Provincial Key Research and Development Program/ ; }, mesh = {Aged ; Humans ; *CD8-Positive T-Lymphocytes ; *COVID-19/metabolism ; Glycogen Synthase Kinase 3 beta/metabolism ; Interferon-gamma/metabolism ; Post-Acute COVID-19 Syndrome ; Programmed Cell Death 1 Receptor/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; }, abstract = {Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8[+] T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8[+] T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8[+] T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3β in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3β. Moreover, AKT decreased PD-1 on CD8[+] T cells, and GSK3β increased PD-1 on CD8[+] T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8[+] T cells by regulating the AKT/GSK3β signaling pathway.}, } @article {pmid38423894, year = {2024}, author = {Johnston, R and Sonnappa, S and Goddings, AL and Whittaker, E and Segal, TY}, title = {A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people.}, journal = {Paediatric respiratory reviews}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.prrv.2024.01.002}, pmid = {38423894}, issn = {1526-0550}, abstract = {Post Covid Syndrome (PCS) is a complex multi-system disorder with a spectrum of presentations. Severity ranges from mild to very severe with variable duration of illness and recovery. This paper discusses the difficulties defining and describing PCS. We review the current understanding of PCS, epidemiology, and predisposing factors. We consider potential mechanisms including viral persistence, clotting dysfunction and immunity. We review presentation and diagnosis and finally consider management strategies including addressing symptom burden, rehabilitation, and novel therapies.}, } @article {pmid38423541, year = {2024}, author = {Ayoubkhani, D and Zaccardi, F and Pouwels, KB and Walker, AS and Houston, D and Alwan, NA and Martin, J and Khunti, K and Nafilyan, V}, title = {Employment outcomes of people with Long Covid symptoms: community-based cohort study.}, journal = {European journal of public health}, volume = {34}, number = {3}, pages = {489-496}, pmid = {38423541}, issn = {1464-360X}, support = {//Department of Health and Social Care/ ; //Welsh Government/ ; //National Institute for Health Research/ ; //Applied Research Collaboration East Midlands/ ; //Leicester Biomedical Research Centre/ ; NIHR200915//Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance/ ; //UK Health Security Agency/ ; //University of Oxford/ ; //Huo Family Foundation/ ; //NIHR Oxford Biomedical Research Centre/ ; //National Health Service/ ; /DH_/Department of Health/United Kingdom ; //Northern Ireland Government/ ; //Scottish Government/ ; //CIS/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; Adult ; *Employment/statistics & numerical data ; Longitudinal Studies ; United Kingdom/epidemiology ; Adolescent ; *SARS-CoV-2 ; Young Adult ; Cohort Studies ; }, abstract = {BACKGROUND: Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and employment outcomes.

METHODS: This was an observational, longitudinal study using a pre-post design. We included survey participants from 3 February 2021 to 30 September 2022 when they were aged 16-64 years and not in education. Using conditional logit modelling, we explored the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks.

RESULTS: Of 206 299 participants (mean age 45 years, 54% female, 92% white), 15% were ever labour market inactive and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks [adjusted odds ratio (aOR): 1.45; 95% CI: 1.17-1.81] or 40 to <52 weeks (aOR: 1.34; 95% CI: 1.05-1.72) post-infection. Combining with official statistics on Long Covid prevalence, and assuming a correct statistical model, our estimates translate to 27 000 (95% CI: 6000-47 000) working-age adults in the UK being inactive because of Long Covid in July 2022.

CONCLUSIONS: Long Covid is likely to have contributed to reduced participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.}, } @article {pmid38421118, year = {2024}, author = {Mattioli, LB and Frosini, M and Corazza, I and Fiorino, S and Zippi, M and Micucci, M and Budriesi, R}, title = {Long COVID-19 gastrointestinal related disorders and traditional Chinese medicine: A network target-based approach.}, journal = {Phytotherapy research : PTR}, volume = {38}, number = {5}, pages = {2323-2346}, doi = {10.1002/ptr.8163}, pmid = {38421118}, issn = {1099-1573}, mesh = {Humans ; *Medicine, Chinese Traditional/methods ; *COVID-19/epidemiology ; *Gastrointestinal Diseases/drug therapy ; *Drugs, Chinese Herbal/therapeutic use ; SARS-CoV-2 ; COVID-19 Drug Treatment ; Pandemics ; }, abstract = {The significant number of individuals impacted by the pandemic makes prolonged symptoms after COVID-19 a matter of considerable concern. These are numerous and affect multiple organ systems. According to the World Health Organization (WHO), prolonged gastrointestinal issues are a crucial part of post-COVID-19 syndrome. The resulting disruption of homeostasis underscores the need for a therapeutic approach based on compounds that can simultaneously affect more than one target/node. The present review aimed to check for nutraceuticals possessing multiple molecular mechanisms helpful in relieving Long COVID-19-specific gastrointestinal symptoms. Specific plants used in Keywords Chinese Medicine (TCM) expected to be included in the WHO Global Medical Compendium were selected based on the following criteria: (1) they are widely used in the Western world as natural remedies and complementary medicine adjuvants; (2) their import and trade are regulated by specific laws that ensure quality and safety (3) have the potential to be beneficial in alleviating intestinal issues associated with Long COVID-19. Searches were performed in PubMed, Elsevier, Google Scholar, Scopus, Science Direct, and ResearchGate up to 2023. Cinnamomum cassia, Glycyrrhiza uralensis, Magnolia officinalis, Poria cocos, Salvia miltiorrhiza, Scutellaria baicalensis, and Zingiber officinalis were identified as the most promising for their potential impact on inflammation and oxidative stress. Based on the molecular mechanisms of the phytocomplexes and isolated compounds of the considered plants, their clinical use may lead to benefits in gastrointestinal diseases associated with Long COVID-19, thanks to a multiorgan and multitarget approach.}, } @article {pmid38420124, year = {2024}, author = {Dongoran, RA and Mardiana, M and Huang, CY and Situmorang, JH}, title = {Boosting NAD+ levels through fasting to aid in COVID-19 recovery.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1319106}, pmid = {38420124}, issn = {1664-3224}, mesh = {Humans ; *NAD ; *COVID-19 ; Fasting ; }, } @article {pmid38419710, year = {2024}, author = {Morelli-Zaher, C and Vremaroiu-Coman, A and Coquoz, N and Genecand, L and Altarelli, M and Binkova, A and Frésard, I and Bridevaux, PO and Gex, G}, title = {Post-COVID central hypersomnia, a treatable trait in long COVID: 4 case reports.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1349486}, pmid = {38419710}, issn = {1664-2295}, abstract = {INTRODUCTION: Fatigue is the most commonly reported post-COVID symptom. A minority of patients also report excessive daytime sleepiness, which could be a target for treatment.

METHODS: Among 530 patients with a post-COVID condition, those with excessive daytime sleepiness were systematically assessed for objective central hypersomnia, with exclusion of all cases not clearly attributable to SARS-CoV-2 infection.

RESULTS: Four cases of post-COVID central hypersomnia were identified, three fulfilling the criteria of the 3rd International Classification of Sleep Disorders for idiopathic hypersomnia, and one for type II narcolepsy. We report here their clinical history, sleep examination data and treatment, with a favorable response to methylphenidate in three cases and spontaneous resolution in one case.

CONCLUSION: We highlight the importance of identifying cases of post-COVID central hypersomnia, as it may be a treatable trait of a post-COVID condition.}, } @article {pmid38418263, year = {2024}, author = {Mitina, A and Khan, M and Lesurf, R and Yin, Y and Engchuan, W and Hamdan, O and Pellecchia, G and Trost, B and Backstrom, I and Guo, K and Pallotto, LM and Lam Doong, PH and Wang, Z and Nalpathamkalam, T and Thiruvahindrapuram, B and Papaz, T and Pearson, CE and Ragoussis, J and Subbarao, P and Azad, MB and Turvey, SE and Mandhane, P and Moraes, TJ and Simons, E and Scherer, SW and Lougheed, J and Mondal, T and Smythe, J and Altamirano-Diaz, L and Oechslin, E and Mital, S and Yuen, RKC}, title = {Genome-wide enhancer-associated tandem repeats are expanded in cardiomyopathy.}, journal = {EBioMedicine}, volume = {101}, number = {}, pages = {105027}, pmid = {38418263}, issn = {2352-3964}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Adult ; *Heart Defects, Congenital/genetics ; Tandem Repeat Sequences/genetics ; DNA Methylation ; *Cardiomyopathies/genetics ; Ontario ; Nerve Tissue Proteins/genetics ; }, abstract = {BACKGROUND: Cardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to heart failure and sudden cardiac death in childhood. While it has a strong genetic basis, the genetic aetiology for over 50% of cardiomyopathy cases remains unknown.

METHODS: In this study, we analyse the characteristics of tandem repeats from genome sequence data of unrelated individuals diagnosed with cardiomyopathy from Canada and the United Kingdom (n = 1216) and compare them to those found in the general population. We perform burden analysis to identify genomic and epigenomic features that are impacted by rare tandem repeat expansions (TREs), and enrichment analysis to identify functional pathways that are involved in the TRE-associated genes in cardiomyopathy. We use Oxford Nanopore targeted long-read sequencing to validate repeat size and methylation status of one of the most recurrent TREs. We also compare the TRE-associated genes to those that are dysregulated in the heart tissues of individuals with cardiomyopathy.

FINDINGS: We demonstrate that tandem repeats that are rarely expanded in the general population are predominantly expanded in cardiomyopathy. We find that rare TREs are disproportionately present in constrained genes near transcriptional start sites, have high GC content, and frequently overlap active enhancer H3K27ac marks, where expansion-related DNA methylation may reduce gene expression. We demonstrate the gene silencing effect of expanded CGG tandem repeats in DIP2B through promoter hypermethylation. We show that the enhancer-associated loci are found in genes that are highly expressed in human cardiomyocytes and are differentially expressed in the left ventricle of the heart in individuals with cardiomyopathy.

INTERPRETATION: Our findings highlight the underrecognized contribution of rare tandem repeat expansions to the risk of cardiomyopathy and suggest that rare TREs contribute to ∼4% of cardiomyopathy risk.

FUNDING: Government of Ontario (RKCY), The Canadian Institutes of Health Research PJT 175329 (RKCY), The Azrieli Foundation (RKCY), SickKids Catalyst Scholar in Genetics (RKCY), The University of Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Centre for Heart Research (SM), Data Sciences Institute at the University of Toronto (SM), The Canadian Institutes of Health Research PJT 175034 (SM), The Canadian Institutes of Health Research ENP 161429 under the frame of ERA PerMed (SM, RL), Heart and Stroke Foundation of Ontario & Robert M Freedom Chair in Cardiovascular Science (SM), Bitove Family Professorship of Adult Congenital Heart Disease (EO), Canada Foundation for Innovation (SWS, JR), Canada Research Chair (PS), Genome Canada (PS, JR), The Canadian Institutes of Health Research (PS).}, } @article {pmid38417769, year = {2024}, author = {Faghy, MA and Dalton, C and Duncan, R and Arena, R and Ashton, REM}, title = {Using cardiorespiratory fitness assessment to identify pathophysiology in long COVID - Best practice approaches.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {55-61}, doi = {10.1016/j.pcad.2024.02.005}, pmid = {38417769}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness ; *COVID-19/physiopathology/diagnosis/epidemiology/therapy ; Exercise Test ; *Post-Acute COVID-19 Syndrome ; }, abstract = {Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body's physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ∼150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.}, } @article {pmid38417766, year = {2024}, author = {Faghy, MA and Tatler, A and Chidley, C and Fryer, S and Stoner, L and Laddu, D and Arena, R and Ashton, RE}, title = {The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {49-54}, doi = {10.1016/j.pcad.2024.02.006}, pmid = {38417766}, issn = {1873-1740}, support = {MRF_MRF-009-0001-RG-TATLE/MRF/MRF/United Kingdom ; }, mesh = {Humans ; *Cardiorespiratory Fitness ; *COVID-19/epidemiology ; *Exercise/physiology ; *Cardiovascular Diseases/epidemiology/physiopathology/prevention & control ; SARS-CoV-2 ; Quality of Life ; }, abstract = {Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.}, } @article {pmid38417420, year = {2024}, author = {van Wincoop, M and Moeniralam, HS and Schramel, FMNH}, title = {Predictors for Long COVID and Differences in Long COVID Symptoms, Findings on Chest Imaging and Pulmonary Function between Hospitalized COVID-19 Patients with versus without Intensive Care Unit Admission.}, journal = {Respiration; international review of thoracic diseases}, volume = {103}, number = {5}, pages = {233-250}, doi = {10.1159/000535391}, pmid = {38417420}, issn = {1423-0356}, mesh = {Humans ; *COVID-19/complications/physiopathology/diagnostic imaging ; Male ; Female ; Middle Aged ; Retrospective Studies ; *Intensive Care Units ; Aged ; *Respiratory Function Tests ; *Tomography, X-Ray Computed ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Lung/diagnostic imaging/physiopathology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {INTRODUCTION: Many COVID-19 survivors suffer from persisting sequelae after acute disease. This is referred to as long COVID. The objectives of this study were to assess factors associated with long COVID and to analyze differences in persistent symptoms, findings on chest imaging, and pulmonary function between intensive care unit (ICU) and non-ICU hospitalized patients.

METHODS: We conducted a retrospective study including patients hospitalized with COVID-19. Patients were stratified into ICU patients and non-ICU patients. We analyzed the outcomes of patients who were in clinical follow-up 6 months after discharge with persistent symptoms, radiological and/or functional abnormalities. Logistic regression was used to examine the association between long COVID and patient characteristics.

RESULTS: A total of 549 patients were included. Eighty-one ICU patients (66%) and 146 (34%) non-ICU patients had persistent symptoms or abnormalities on chest imaging or lung function test minimally 6 months after discharge. Significantly more ICU patients had residual fibrotic abnormalities on chest CT and functional impairment. Female gender, myocardial infarction, OSAS, low PCO2 at admission, and longer hospital stay were associated with a higher risk of developing long COVID. Diabetes and treatment with tocilizumab were associated with a lower risk of developing long COVID.

CONCLUSION: Of the patients hospitalized for COVID-19, 34-66% suffered from persistent symptoms, residual abnormalities on chest imaging, or reduced lung function at around 6 months after discharge. While persistent sequelae were more frequent in ICU patients, admission to the ICU was not found to be an independent risk factor for developing long COVID.}, } @article {pmid38416635, year = {2024}, author = {Parreira, LFS and Pinheiro, SL and Fontana, CE}, title = {Photobiomodulation in the Treatment of Dysgeusia in Patients with Long COVID: A Single-Blind, Randomized Controlled Trial.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {42}, number = {3}, pages = {215-224}, doi = {10.1089/photob.2023.0148}, pmid = {38416635}, issn = {2578-5478}, mesh = {Humans ; *COVID-19/radiotherapy ; Dysgeusia/etiology/radiotherapy ; *Low-Level Light Therapy ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Randomized Controlled Trials as Topic ; Single-Blind Method ; }, abstract = {Objective: The aim of this study is to evaluate local and systemic photobiomodulation (PBM) in patients with COVID-19-related dysgeusia, with the expectation of improving taste dysfunction. Background: PBM has garnered attention as a potential therapy in long COVID, a condition characterized by many persistent symptoms following the acute phase of COVID-19. Among these symptoms, dysgeusia, or altered taste perception, can significantly affect patients' quality of life. Emerging research suggests that PBM may hold promise in ameliorating dysgeusia by modulating cellular processes and reducing inflammation. Further clinical studies and randomized controlled trials are essential to establish the efficacy and safety of PBM for the treatment of dysgeusia in long COVID, but initial evidence suggests that this noninvasive modality may offer a novel avenue for symptom management. Methods: Seventy patients experiencing dysgeusia were randomly assigned to receive active local and systemic PBM (n = 34) or simulated PBM (n = 36). Low-power laser (red wavelength) was used at 18 spots on the lateral borders of the tongue (3 J per spot), salivary glands (parotid, sublingual, and submandibular glands-3 J per spot), and over the carotid artery for 10 min (60 J). Alongside laser therapy, all patients in both groups received weekly olfactory therapy for up to 8 weeks. Results: Dysgeusia improved in both groups. At weeks 7 and 8, improvement scores were significantly higher in the PBM group than in the sham group (p = 0.048). Conclusions: Combined local and systemic PBM, as applied in this study, proved effective and could serve as a viable treatment option for alleviating dysgeusia in long-COVID patients. Clinical Trial Registration: RBR-2mfbkkk.}, } @article {pmid38416434, year = {2024}, author = {Al-Aly, Z and Rosen, CJ}, title = {Long Covid and Impaired Cognition - More Evidence and More Work to Do.}, journal = {The New England journal of medicine}, volume = {390}, number = {9}, pages = {858-860}, pmid = {38416434}, issn = {1533-4406}, mesh = {Humans ; Cognition ; COVID-19/complications ; *Post-Acute COVID-19 Syndrome/etiology ; *Cognition Disorders/etiology ; }, } @article {pmid38415507, year = {2024}, author = {Xiao, J and Luo, Y and Li, Y and Yao, X}, title = {The characteristics of BCR-CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccinated volunteers.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29488}, doi = {10.1002/jmv.29488}, pmid = {38415507}, issn = {1096-9071}, support = {82160279//National Natural Science Foundation of China/ ; (2018) 5637//Guizhou Provincial Hundred Level Talent Fund/ ; }, mesh = {Humans ; *SARS-CoV-2/genetics ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Pandemics ; Antibodies, Neutralizing ; Antibodies, Viral ; }, abstract = {The global COVID-19 pandemic has caused more than 1 billion infections, and numerous SARS-CoV-2 vaccines developed rapidly have been administered over 10 billion doses. The world is continuously concerned about the cytokine storms induced by the interaction between SARS-CoV-2 and host, long COVID, breakthrough infections postvaccination, and the impact of SARS-CoV-2 variants. BCR-CDR3 repertoire serves as a molecular target for monitoring the antiviral response "trace" of B cells, evaluating the effects, mechanisms, and memory abilities of individual responses to B cells, and has been successfully applied in analyzing the infection mechanisms, vaccine improvement, and neutralizing antibodies preparation of influenza virus, HIV, MERS, and Ebola virus. Based on research on BCR-CDR3 repertoire of COVID-19 patients and volunteers who received different SARS-CoV-2 vaccines in multiple laboratories worldwide, we focus on analyzing the characteristics and changes of BCR-CDR3 repertoire, such as diversity, clonality, V&J genes usage and pairing, SHM, CSR, shared CDR3 clones, as well as the summary on BCR sequences targeting virus-specific epitopes in the preparation and application research of SARS-CoV-2 potential therapeutic monoclonal antibodies. This review provides comparative data and new research schemes for studying the possible mechanisms of differences in B cell response between SARS-CoV-2 infection or vaccination, and supplies a foundation for improving vaccines after SARS-CoV-2 mutations and potential antibody therapy for infected individuals.}, } @article {pmid38415466, year = {2024}, author = {Çitil, S and Aksu, Y}, title = {Does Postlong Coronavirus 2019 Disease Affect Renal Stiffness without any Chronic Systemic Disorders?.}, journal = {Current medical imaging}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115734056258544231115103528}, pmid = {38415466}, issn = {1573-4056}, abstract = {BACKGROUND: In the last few years, coronavirus disease 2019 (COVID-19) has changed human lifestyle, behavior, and perception of life. This disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). In the literature, there are limited studies about the late renal effects of COVID-19 that reflect the systemic involvement of this disease.

AIM: In the present study, we aimed to compare sonoelastographic changes in both kidneys between patients who had totally recovered from COVID-19 and healthy individuals using strain wave elastography (SWE).

METHODS: This study was conducted between June 2021 and May 2022 in Kahramanmaraş City Hospital Department of Radiology. File and archive records were retrospectively evaluated. Basic demographic, laboratory, and renal ultrasonography (USG) and sonoelastographic findings were screened and noted. Two groups were defined to compare sonoelastographic findings. Post-long COVID-19 group had 92 post-long COVID-19 patients, and the comparator group had 9 healthy individuals". Both groups' demographic, laboratory, and ultrasound-elastographic findings were assessed.

RESULTS: The post-long COVID-19 group had a higher renal elastographic value than the comparator group (1.52 [0.77-2.3] vs. 0.96 [0.54-1.54], p<0.001). There were no statistically significant differences between the two groups in terms of age (p=0.063), gender (p=0.654), or body mass index (BMI) (p=0.725), however, there was a significant difference observed between the two groups in the renal strain ratio (RSR). According to an ROC analysis, an RSR cutoff of >1.66 predicted post-long COVID-19 with 44.9% sensitivity and 81.9% specificity. (AUC=0.655, p<0.001). A separate ROC analysis was performed to predict post-long COVID-19 with a BMI cutoff of <33.52, kg/m2 sensitivity of 92.4% and specificity of 17% (AUC=0.655, p<0.001).

CONCLUSION: We demonstrated that renal parenchymal stiffness increases with SWE in post-long COVID-19 patients.}, } @article {pmid38414563, year = {2024}, author = {Estebanez-Pérez, MJ and Pastora-Bernal, JM and Vinolo-Gil, MJ and Pastora-Estebanez, P and Martín-Valero, R}, title = {Digital physiotherapy is a satisfactory and effective method to improve the quality of life in Long COVID patients.}, journal = {Digital health}, volume = {10}, number = {}, pages = {20552076241234432}, pmid = {38414563}, issn = {2055-2076}, abstract = {OBJECTIVE: This research aimed to explore Long COVID patient's quality of life, satisfaction and perception with an individualized and customizable digital physiotherapy intervention during a 4-week period.

METHODS: A pre-post clinical trial was conducted with 32 Long COVID patients. Quality of life was assessed using the 12-Item Short Form Survey and the European Quality of Life-5 Dimensions questionnaire (EuroQol-5D), while satisfaction and perception were measured using the Telemedicine Satisfaction Questionnaire. Optional open-ended questions were added as qualitative approach. A mixed design method was conducted.

RESULTS: After intervention, a statistically significant improvement (p < 0.05) was observed in quality of life. The SF-12 questionnaire showed an increase of 4.04 points in the physical component and 6.55 points in the mental component with a small/medium effect size. The EuroQoL-5D questionnaire demonstrated a medium effect size with an increase of 0.87 points. Patient perception indicated high rates of satisfaction and values above the minimal clinically important difference. The qualitative approach revealed several interesting findings.

CONCLUSION: Participants found the digital intervention satisfactory and effective in improving their quality of life. Suggestions for improvement, such as the inclusion of face-to-face sessions, a chat for immediate contact, sound in breath exercises in the digital program, longer duration and continuity of intervention, were mentioned. Larger sample studies and in-deep qualitative methodologies are needed to draw extrapolable conclusions.

TRIAL REGISTRATION: NCT04742946.}, } @article {pmid38413755, year = {2024}, author = {Jamoulle, M and Louazon, E and Antonacci, T and Van Weyenbergh, J}, title = {Speed up relief for long COVID through grassroots clinical trials.}, journal = {Nature}, volume = {626}, number = {8001}, pages = {954}, doi = {10.1038/d41586-024-00560-4}, pmid = {38413755}, issn = {1476-4687}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/therapy ; *Clinical Trials as Topic/methods/organization & administration ; Time Factors ; }, } @article {pmid38413454, year = {2024}, author = {Bonnet, U and Kuhn, J}, title = {Serotonin deficiency and psychiatric long COVID: both caused specifically by the virus itself or an adaptive general stress response?.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {38413454}, issn = {1433-8491}, } @article {pmid38413389, year = {2024}, author = {Lopuhaä, B and Voorham, QJM and van Kemenade, FJ and von der Thüsen, JH}, title = {COVID-19 in the Netherlands: lessons from a nationwide query of dutch autopsy, histology, and cytology pathological reports.}, journal = {Virchows Archiv : an international journal of pathology}, volume = {484}, number = {3}, pages = {429-439}, pmid = {38413389}, issn = {1432-2307}, support = {10430012010016/ZONMW_/ZonMw/Netherlands ; }, mesh = {Female ; Humans ; Pregnancy ; Autopsy ; *COVID-19/pathology ; Lung/pathology ; Netherlands/epidemiology ; Pandemics ; *Pregnancy Complications, Infectious/pathology ; SARS-CoV-2 ; *Thrombosis/pathology ; }, abstract = {Since the onset of the COVID-19 pandemic, autopsies have played a valuable role in understanding the pathophysiology of COVID-19. In this study, we have analyzed COVID-19-related pathology reports from autopsies, histology, and cytology on a nationwide level. Pathology reports from all 43 pathology laboratories in the Netherlands stating "COVID," "Corona," and/or "SARS" were queried from the Dutch Nationwide Pathology Database (Palga). Consecutive reports of the included patients were also retrieved. Out of 5065 entries, a total of 1833 eligible COVID-19-related pathology reports between January 2020 and June 2021 were included in this collection of reports. Lung histopathology reports reflected differences in the severity of abnormalities (acute diffuse alveolar damage, alveolar histiocytes, and thrombi during the first three pandemic waves (Wuhan variant) versus the fourth wave (alpha variant)). Autopsy reports from 2020 state significantly shorter disease duration and younger age of death compared to autopsy reports from 2021. All reports together reflected a more granular pathology with comorbidities such as chronic histiocytic intervillositis, perniosis, and thrombi found in a variety of organs (lungs, kidneys, and small and large intestines). This nationwide overview of pathology reports provides data related to deaths as well as comorbidities in a clinical setting of COVID-19. Certain findings reported in SARS-CoV-infected lungs and placentas were also reported in post-COVID-19 tissue of the same kind. Consecutive reports after the earliest reports with COVID-19 allowed for follow-up reports. These follow-up reports can help with post-viral studies regarding long-term effects of COVID-19 as well as identifying the effects of different SARS-CoV-2 variants.}, } @article {pmid38413334, year = {2024}, author = {Soriano, JB}, title = {Potential Benefits of a Cardiovascular Polypill in Long COVID Patients.}, journal = {Archivos de bronconeumologia}, volume = {60}, number = {5}, pages = {263-264}, doi = {10.1016/j.arbres.2024.02.003}, pmid = {38413334}, issn = {1579-2129}, mesh = {Humans ; *COVID-19 Drug Treatment ; *COVID-19/prevention & control/complications ; Drug Combinations ; Aged ; Cardiovascular Agents/administration & dosage/therapeutic use ; Male ; SARS-CoV-2 ; Female ; Cardiovascular Diseases/prevention & control ; }, } @article {pmid38410853, year = {2024}, author = {Mirbadie, SR and Taheri, A and Roshanzamir, E and Soleymani, E and Fakhar, M}, title = {Severe lophomoniasis in a patient with diabetes and past history of COVID-19 in Central Iran: case report.}, journal = {The Journal of international medical research}, volume = {52}, number = {2}, pages = {3000605241232917}, pmid = {38410853}, issn = {1473-2300}, mesh = {Humans ; Female ; *Protozoan Infections/complications/diagnosis ; *Lung Diseases, Parasitic/diagnosis/drug therapy/etiology ; Iran ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Diabetic Ketoacidosis/complications ; *Diabetes Mellitus ; }, abstract = {In this case report, we address the diagnostic challenges and clinical implications of severe infection with Lophomonas blattarum in a patient initially suspected of experiencing long COVID symptoms. We describe the patient's medical history, initial symptoms, diagnostic tests, and treatment. A female patient with diabetes in her early 60s presented with severe shortness of breath and was initially diagnosed with diabetic ketoacidosis (DKA). After resolution of her DKA symptoms, persistent respiratory issues led to a COVID-19 test, which was negative. A chest computed tomography scan revealed abnormalities, prompting bronchoscopy and bronchoalveolar lavage fluid analysis, which confirmed the presence of L. blattarum. Notably, the protozoan remained mobile and viable even after a 4-day transport at ambient temperature. This case emphasizes the importance of considering alternative diagnoses and improving awareness about L. blattarum infection in patients with respiratory symptoms, for timely and accurate management.}, } @article {pmid38410661, year = {2024}, author = {, }, title = {Erratum: The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1380811}, doi = {10.3389/fpubh.2024.1380811}, pmid = {38410661}, issn = {2296-2565}, abstract = {[This corrects the article DOI: 10.3389/fpubh.2023.1303183.].}, } @article {pmid38407808, year = {2024}, author = {Buckley, ML and Wycoff, AM and Mahoney, K and Pierce, JF and Simmons, J and Adami, A}, title = {Improvements in Dyspnea Following Traditional Pulmonary Rehabilitation in Patients With Long COVID.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {44}, number = {2}, pages = {141-143}, pmid = {38407808}, issn = {1932-751X}, support = {R01 HL151452/HL/NHLBI NIH HHS/United States ; T32 AA007459/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Dyspnea/etiology ; }, } @article {pmid38406111, year = {2024}, author = {Assiri, AM and Alamaa, T and Elenezi, F and Alsagheir, A and Alzubaidi, L and TIeyjeh, I and Alhomod, AS and Gaffas, EM and Amer, SA}, title = {Unveiling the Clinical Spectrum of Post-COVID-19 Conditions: Assessment and Recommended Strategies.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52827}, pmid = {38406111}, issn = {2168-8184}, abstract = {SARS-CoV-2 caused the pandemic of the rapidly evolving COVID-19. As of December 6, 2023, there were 765,152,854 COVID-19-recovering cases. Long-term consequences known as "long COVID" and "post-COVID-19 conditions" (PCCs) or "post-acute COVID-19 syndrome" are being reported more frequently in a subset of recovering patients. Systemic, neuropsychiatric, cardio-respiratory, and gastrointestinal symptoms are the most prevalent. The management of PCCs poses unique challenges due to the lack of official guidelines and the complex nature of the illness. This abstract highlights key principles derived from recent reviews and expert recommendations to provide healthcare professionals with a comprehensive approach to manage post-COVID-19 patients. Preventive medicine plays a crucial role in managing PCCs. While no specific medications are available for treatment, preventive measures such as COVID-19 vaccination, adherence to precautionary measures, regular consultations with medical professionals, monitoring symptoms and progress, and seeking information on symptom management are essential to assist patients in their recovery and improve their quality of life. Medical management requires transparent goal-setting and collaborative decision-making based on the patient's symptoms, comorbidities, and treatment objectives. Treatment plans for post-COVID-19 patients should focus on patient education, using registries and calendars to track symptoms and triggers, providing support and reassurance, and offering holistic support through peer networks and supportive psychotherapy techniques. Symptomatic and rehabilitative care, including well-established symptom management techniques, physical rehabilitation programs, and addressing mental health and well-being, are vital components of post-COVID-19 management. Lifestyle factors such as stress reduction, nutrition, and sleep should be incorporated into managing underlying medical conditions in post-COVID-19 patients. Regular follow-up visits and referrals to specialists are recommended to monitor the patient's progress and address specific organ system involvement or additional care needs. In summary, for the effective management of PCCs, a holistic approach should include preventive measures, patient education, supportive psychotherapy, symptomatic and rehabilitative care, medical management, counseling on lifestyle elements, and appropriate follow-up plans. However, it is crucial to stay updated with evolving guidelines and recommendations from healthcare authorities to provide the most effective and evidence-based care to post-COVID-19 patients.}, } @article {pmid38405753, year = {2024}, author = {Patton, MJ and Benson, D and Robison, SW and Dhaval, R and Locy, ML and Patel, K and Grumley, S and Levitan, EB and Morris, P and Might, M and Gaggar, A and Erdmann, N}, title = {Characteristics and Determinants of Pulmonary Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.13.24302781}, pmid = {38405753}, abstract = {RATIONALE: Persistent cough and dyspnea are prominent features of post-acute sequelae of SARS-CoV-2 (termed 'Long COVID'); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined.

OBJECTIVES: Using longitudinal pulmonary function testing (PFTs) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary Long COVID.

METHODS: The University of Alabama at Birmingham Pulmonary Long COVID cohort was utilized to characterize lung defects in patients with persistent pulmonary symptoms after resolution primary COVID infection. Longitudinal PFTs including total lung capacity (TLC) and diffusion limitation of carbon monoxide (DLCO) were used to evaluate restriction and diffusion impairment over time in this cohort. Analysis of chest CT imaging was used to phenotype the pulmonary Long COVID pathology. Risk factors linked to development of pulmonary Long COVID were estimated using univariate and multivariate logistic regression models.

MEASUREMENTS AND MAIN RESULTS: Longitudinal evaluation 929 patients with post-COVID pulmonary symptoms revealed diffusion impairment (DLCO ≤80%) and restriction (TLC ≤80%) in 51% of the cohort (n=479). In multivariable logistic regression analysis (adjusted odds ratio; aOR, 95% confidence interval [CI]), invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary Long COVID with diffusion impaired restriction (aOR=10.9 [4.09-28.6]). Finally, a sub-analysis of CT imaging identified evidence of fibrosis in this population.

CONCLUSIONS: Persistent diffusion impaired restriction was identified as a key feature of pulmonary Long COVID. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary Long COVID patients.}, } @article {pmid38405190, year = {2024}, author = {Chu, XJ and Song, DD and Zhou, MH and Chen, XZ and Chu, N and Li, M and Li, BZ and Liu, SH and Hou, S and Wu, JB and Gong, L}, title = {Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1301312}, pmid = {38405190}, issn = {2296-858X}, abstract = {OBJECTIVES: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients.

METHODS: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis.

RESULTS: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients.

CONCLUSION: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.}, } @article {pmid38404605, year = {2024}, author = {Bratty, AJ}, title = {Neuroplasticity Intervention, Amygdala and Insula Retraining (AIR), Significantly Improves Overall Health and Functioning Across Various Chronic Conditions.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {22}, number = {6}, pages = {20-28}, pmid = {38404605}, issn = {1546-993X}, abstract = {Chronic conditions, sometimes referred to as functional somatic disorders, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently, long COVID (LC), affect millions of people worldwide. Yet, after decades of research and testing, the etiology and treatment for many of these diseases is still unclear. Recently, a consortium of clinicians and researchers have proposed that while many different chronic conditions exist, the root cause of each may be a similar brain-body connection, as the brain responds to perceived biological threats and transmits danger signals to the body that manifest as somatic symptoms. This hypothesis suggests that treating chronic conditions requires an approach that addresses the neural networks involved. One such method, known as Amygdala and Insula Retraining (AIR), otherwise known as The Gupta Program, has shown promise in recent years for treating such conditions, including ME/CFS, FM, and LC. The present study aimed to demonstrate that AIR could be an effective approach for numerous other chronic illnesses (e.g., Lyme disease, mold illness, mast cell activation syndrome [MCAS]) and others. This novel and exploratory research examined self-reported health and functioning levels before and after using AIR. A series of paired-sample t tests with Bonferroni correction demonstrated that after 3+ months of using AIR (the minimum recommended time for the intervention), participants experienced a significant increase in overall health and functioning for 14 of 16 conditions tested (P < .001 for all but one, which was P = .001) and approached significance for the remaining two conditions (P = .039 and P = .005). Of the 14 signficant findings, 11 had a large effect size and three had a medium effect size. Naturally, this study has limitations. It was a cross-sectional design with a small convenience sample and self-reported data. Future research with larger samples and randomized controlled trials is needed to provide further evidence of AIR's effectiveness. Nonetheless, these preliminary findings suggest that AIR is a viable method for improving the health of people suffering from chronic conditions, and clinicians and researchers might consider incorporating AIR into their protocols for these patients.}, } @article {pmid38403179, year = {2024}, author = {Sanal-Hayes, NEM and Hayes, LD and Mclaughlin, M and Berry, ECJ and Sculthorpe, NF}, title = {People with Long COVID and ME/CFS Exhibit Similarly Impaired Dexterity and Bimanual Coordination: A Case-Case-Control Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.02.003}, pmid = {38403179}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {PURPOSE: Dexterity and bimanual coordination had not previously been compared between people with long COVID and people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Therefore, this study determined dexterity and bimanual coordination in people with long COVID (∼16-month illness duration; n = 21) and ME/CFS (∼16-year illness duration; n = 20), vs age-matched healthy controls (n = 20).

METHODS: Dexterity and bimanual coordination was determined using the Purdue pegboard test.

RESULTS: The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable for Purdue pegboard tests (P > .556 and d < 0.36 for pairwise comparisons). It is worth noting however, that both these patient groups performed poorer in the Perdue pegboard test than healthy controls (P < .169 and d > 0.40 for pairwise comparisons).

CONCLUSIONS: These data suggest that both people with long COVID and people with ME/CFS have similarly impaired dexterity and bimanual coordination. Therefore, there is an urgent need for interventions to target dexterity and bimanual coordination in people with ME/CFS, and given the current pandemic, people with long COVID.}, } @article {pmid38401674, year = {2024}, author = {Quan, SF and Weaver, MD and Czeisler, MÉ and Barger, LK and Booker, LA and Howard, ME and Jackson, ML and Lane, RI and McDonald, CF and Ridgers, A and Robbins, R and Varma, P and Wiley, JF and Rajaratnam, SMW and Czeisler, CA}, title = {Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 Infection.}, journal = {The American journal of medicine}, volume = {137}, number = {6}, pages = {529-537.e3}, pmid = {38401674}, issn = {1555-7162}, support = {K01 HL150339/HL/NHLBI NIH HHS/United States ; R01 OH011773/OH/NIOSH CDC HHS/United States ; R01OH011773/ACL/ACL HHS/United States ; R56 HL151637/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Sleep Apnea, Obstructive/epidemiology/complications ; *COVID-19/complications/epidemiology ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; *Post-Acute COVID-19 Syndrome ; Aged ; Risk Factors ; United States/epidemiology ; SARS-CoV-2 ; Prevalence ; }, abstract = {BACKGROUND: Obstructive sleep apnea is associated with COVID-19 infection. Less clear is whether obstructive sleep apnea is a risk factor for the development of post-acute sequelae of SARS-CoV-2 infection (PASC).

STUDY DESIGN: Cross-sectional survey of a general population of 24,803 US adults to determine the association of obstructive sleep apnea with PASC.

RESULTS: COVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence of persistent (>3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models, obstructive sleep apnea was associated with all putative PASC-related symptoms with the highest adjusted odds ratios being fever (2.053) and nervous/anxious (1.939). In 4 logistic regression models of overall PASC derived from elastic net regression, obstructive sleep apnea was associated with PASC (range of adjusted odds ratios: 1.934-2.071); this association was mitigated in those with treated obstructive sleep apnea. In the best fitting overall model requiring ≥3 symptoms, PASC prevalence was 21.9%.

CONCLUSION: In a general population sample, obstructive sleep apnea is associated with the development of PASC-related symptoms and a global definition of PASC. Treated obstructive sleep apnea mitigates the latter risk. The presence of 3 or more PASC symptoms may be useful in identifying cases and for future research.}, } @article {pmid38400407, year = {2024}, author = {Kowal, M and Morgiel, E and Winiarski, S and Dymarek, R and Bajer, W and Madej, M and Sebastian, A and Madziarski, M and Wedel, N and Proc, K and Madziarska, K and Wiland, P and Paprocka-Borowicz, M}, title = {Ebbing Strength, Fading Power: Unveiling the Impact of Persistent Fatigue on Muscle Performance in COVID-19 Survivors.}, journal = {Sensors (Basel, Switzerland)}, volume = {24}, number = {4}, pages = {}, pmid = {38400407}, issn = {1424-8220}, support = {SUBZ.E060.24.036//Ministry of Science and Higher Education of Poland/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *Carcinoma, Hepatocellular ; *COVID-19 ; SARS-CoV-2 ; *Liver Neoplasms ; Muscle, Skeletal/physiology ; Muscle Strength/physiology ; Fatigue ; Survivors ; }, abstract = {The total number of confirmed cases of COVID-19 caused by SARS-CoV-2 virus infection is over 621 million. Post-COVID-19 syndrome, also known as long COVID or long-haul COVID, refers to a persistent condition where individuals experience symptoms and health issues after the acute phase of COVID-19. The aim of this study was to assess the strength and fatigue of skeletal muscles in people recovered from COVID-19. A total of 94 individuals took part in this cross-sectional study, with 45 participants (referred to as the Post-COVID Cohort, PCC) and 49 healthy age-matched volunteers (Healthy Control Cohort, HCC). This research article uses the direct dynamometry method to provide a detailed analysis of post-COVID survivors' strength and power characteristics. The Biodex System 4 Pro was utilized to evaluate muscle strength characteristics during the fatigue test. The fatigue work in extensors and flexors was significantly higher in the PCC. The PCC also showed significantly less power in both extensors and flexors compared to the HCC. In conclusion, this study provides compelling evidence of the impact of post-COVID-19 fatigue on muscle performance, highlighting the importance of considering these effects in the rehabilitation and care of individuals recovering from the virus. PCC achieved lower muscle strength values than HCC.}, } @article {pmid38400172, year = {2024}, author = {Man, MA and Rosca, D and Bratosin, F and Fira-Mladinescu, O and Ilie, AC and Burtic, SR and Fildan, AP and Fizedean, CM and Jianu, AM and Negrean, RA and Marc, MS}, title = {Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis.}, journal = {Vaccines}, volume = {12}, number = {2}, pages = {}, pmid = {38400172}, issn = {2076-393X}, abstract = {This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces the risk and severity of post-COVID-19 syndrome. In October 2023, a comprehensive literature search was conducted across three databases, PubMed, Embase, and Scopus, focusing on studies published up to that date. Utilizing a wide array of keywords, the search strategy adhered to the PRISMA guidelines and was registered in the Open Science Framework. The inclusion criteria comprised studies focusing on patients with a breakthrough SARS-CoV-2 infection who developed post-COVID-19 syndrome. We included a total of 13 articles that met the inclusion criteria, analyzing more than 10 million patients with a mean age of 50.6 years, showing that the incidence of intensive care unit (ICU) admissions post-vaccination was as low as 2.4%, with a significant reduction in mortality risk (OR 0.66, 95% CI 0.58-0.74). The prevalence of post-COVID-19 syndrome symptoms was lower in vaccinated individuals (9.5%) compared to unvaccinated (14.6%), with a notable decrease in activity-limiting symptoms (adjusted OR 0.59, 95% CI 0.48-0.73). Vaccinated patients also showed a quicker recovery and return to work (HR 1.37, 95% CI 1.04-1.79). The pooled odds ratio of 0.77 indicates that vaccination is associated with a 23% reduction in the risk of developing post-COVID-19 syndrome (95% CI 0.75-0.79). Despite the protective effects observed, a substantial heterogeneity among the studies was noted. In conclusion, a pre-infection COVID-19 vaccination is associated with a significant reduction in the risk and severity of post-COVID-19 syndrome. However, the observed heterogeneity across studies suggests a need for further research with standardized methods to fully comprehend vaccine efficacy against long COVID.}, } @article {pmid38400166, year = {2024}, author = {Di Fusco, M and Sun, X and Allen, KE and Yehoshua, A and Berk, A and Alvarez, MB and Porter, TM and Ren, J and Puzniak, L and Lopez, SMC and Cappelleri, JC}, title = {Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.}, journal = {Vaccines}, volume = {12}, number = {2}, pages = {}, pmid = {38400166}, issn = {2076-393X}, support = {not available//Pfizer Inc./ ; }, abstract = {BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms.

METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates.

RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue.

CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.}, } @article {pmid38400050, year = {2024}, author = {Fernández-de-Las-Peñas, C and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Torres-Macho, J and Ryan-Murua, P and Franco-Moreno, AI and Pellicer-Valero, OJ and Arendt-Nielsen, L and Giordano, R}, title = {Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.}, journal = {Viruses}, volume = {16}, number = {2}, pages = {}, pmid = {38400050}, issn = {1999-4915}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/genetics ; Interleukin-10/genetics ; Interleukin-6/genetics ; Membrane Proteins/genetics ; Polymorphism, Single Nucleotide ; RNA-Binding Proteins/genetics ; SARS-CoV-2/genetics ; *Tumor Necrosis Factor-alpha/genetics ; }, abstract = {The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252, were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.}, } @article {pmid38399972, year = {2024}, author = {Frank, N and Dickinson, D and Garcia, W and Liu, Y and Yu, H and Cai, J and Patel, S and Yao, B and Jiang, X and Hsu, S}, title = {Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID.}, journal = {Viruses}, volume = {16}, number = {2}, pages = {}, pmid = {38399972}, issn = {1999-4915}, support = {1R41DC020678-01/NH/NIH HHS/United States ; }, mesh = {Humans ; United States ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/pharmacology ; Feasibility Studies ; Saline Solution ; Inflammation ; Lipids ; Catechin/*analogs & derivatives ; }, abstract = {UNLABELLED: A recent estimate indicates that up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to associated symptoms, leading to a USD 50 billion annual loss of salary. Post-COVID (Long COVID) neurologic symptoms are due to the initial robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation of the olfactory epithelium (OE) and the central nervous system (CNS), and the OE becoming a persistent infection site. Previously, our group showed that Epigallocatechin-3-gallate-palmitate (EC16) nanoformulations possess strong antiviral activity against human coronavirus, suggesting this green tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug to eliminate the persistent SARS-CoV-2 infection, leading to restored olfactory function and reduced inflammation in the CNS. The objective of the current study was to determine the compatibility of the nanoformulations with human nasal primary epithelial cells (HNpECs).

METHODS: Nanoparticle size was measured using the ZetaView Nanoparticle Tracking Analysis (NTA) system; contact antiviral activity was determined by TCID50 assay for cytopathic effect on MRC-5 cells; post-infection inhibition activity was determined in HNpECs; and cytotoxicity for these cells was determined using an MTT assay. The rapid inactivation of OC43 (a β-coronavirus) and 229E (α-coronavirus) viruses was further characterized by transmission electron microscopy.

RESULTS: A saline-based nanoformulation containing 0.1% w/v EC16 was able to inactivate 99.9999% β-coronavirus OC43 on direct contact within 1 min. After a 10-min incubation of infected HNpECs with a formulation containing drug-grade EC16 (EGCG-4' mono-palmitate or EC16m), OC43 viral replication was inhibited by 99%. In addition, all nanoformulations tested for their effect on cell viability were comparable to normal saline, a regularly used nasal irrigation solution. A 1-min incubation of an EC16 nanoformulation with either OC43 or 229E showed an altered viral structure.

CONCLUSION: Nanoformulations containing EC16 showed properties compatible with nasal application to rapidly inactivate SARS-CoV-2 residing in the olfactory mucosa and to reduce inflammation in the CNS, pending additional formulation and safety studies.}, } @article {pmid38399736, year = {2024}, author = {Liu, S and Zhong, M and Wu, H and Su, W and Wang, Y and Li, P}, title = {Potential Beneficial Effects of Naringin and Naringenin on Long COVID-A Review of the Literature.}, journal = {Microorganisms}, volume = {12}, number = {2}, pages = {}, pmid = {38399736}, issn = {2076-2607}, support = {2023A1515011953//Natural Science Foundation of Guangdong Province/ ; 2022SDZG07//Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province/ ; 2022ZD006//Research Fund of Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.}, } @article {pmid38399677, year = {2024}, author = {Hussain, H and Paidas, MJ and Rajalakshmi, R and Fadel, A and Ali, M and Chen, P and Jayakumar, AR}, title = {Dermatologic Changes in Experimental Model of Long COVID.}, journal = {Microorganisms}, volume = {12}, number = {2}, pages = {}, pmid = {38399677}, issn = {2076-2607}, support = {n/a//University of Miami Health System/ ; }, abstract = {The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.}, } @article {pmid38399482, year = {2024}, author = {Wirth, KJ and Löhn, M}, title = {Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Evolving from the Post COVID-19 Syndrome.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {2}, pages = {}, pmid = {38399482}, issn = {1648-9144}, mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology ; Post-Acute COVID-19 Syndrome ; Capillaries ; Microcirculation ; *COVID-19/complications/metabolism ; Mitochondria/metabolism ; Perfusion ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID-19 Syndrome (PCS). A fraction of the PCS patients develop the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and the expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing the constriction of resistance vessels and of precapillary sphincters, which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis, which is already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of microcirculatory and precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in predisposed patients because the interaction causes a particular kind of perfusion disturbance-capillary ischemia/reperfusion-which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter, in turn, worsens the vascular situation through the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.}, } @article {pmid38398746, year = {2024}, author = {Baroni, M and Beltrami, S and Schiuma, G and Ferraresi, P and Rizzo, S and Passaro, A and Molina, JMS and Rizzo, R and Di Luca, D and Bortolotti, D}, title = {In Situ Endothelial SARS-CoV-2 Presence and PROS1 Plasma Levels Alteration in SARS-CoV-2-Associated Coagulopathies.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {38398746}, issn = {2075-1729}, support = {FAR 2022//University of Ferrara/ ; FIRD 2023//University of Ferrara/ ; CROWDFUNDING//University of Ferrara/ ; 5X1000//University of Ferrara/ ; }, abstract = {BACKGROUND: Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To date, the mechanism underlying the alteration of the coagulation cascade in COVID-19 patients remains misunderstood and the anticoagulant protein S (PROS1) has been described as a potential risk factor for complications related to COVID-19, due to PLpro SARS-CoV-2 enzyme proteolysis.

METHODS: Biopsies and blood samples were collected from SARS-CoV-2 positive and negative swab test subjects with coagulopathies (peripheral arterial thrombosis), and SARS-CoV-2 presence, ACE2 and CD147 expression, and plasmatic levels of PROS1 were evaluated.

RESULTS: We reported a significant decrease of plasmatic PROS1 in the coagulopathic SARS-CoV-2 swab positive cohort, in association with SARS-CoV-2 in situ infection and CD147 peculiar expression. These data suggested that SARS-CoV-2 associated thrombotic/ischemic events might involve PROS1 cleavage by viral PLpro directly in the site of infection, leading to the loss of its anticoagulant function.

CONCLUSIONS: Based on this evidence, the identification of predisposing factors, such as CD147 increased expression, and the use of PLpro inhibitors to preserve PROS1 function, might be useful for COVID-19 coagulopathies management.}, } @article {pmid38398462, year = {2024}, author = {Bota, AV and Bratosin, F and Bandi, SSS and Bogdan, I and Razvan, DV and Toma, AO and Indries, MF and Csep, AN and Cotoraci, C and Prodan, M and Marc, F and Ignuta, F and Marincu, I}, title = {A Comparative Analysis of Liver Injury Markers in Post-COVID Syndrome among Elderly Patients: A Prospective Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {4}, pages = {}, pmid = {38398462}, issn = {2077-0383}, abstract = {BACKGROUND: In the wake of the global COVID-19 pandemic, understanding its prolonged impact on vulnerable populations has become a critical area of investigation. This study aimed to elucidate the distinctive post-acute sequelae of SARS-CoV-2 infection (PASC) and liver injury in Romania's elderly population, hypothesizing unique demographic, clinical, and healthcare factors influencing the manifestation.

METHODS: A longitudinal design was employed, enrolling COVID-19 patients from the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania. Participants were stratified into three groups based on age and Long COVID status. The study focused on a variety of demographic, clinical, and biological parameters, including liver function tests, to assess the trajectory and severity of liver injury over six months post discharge.

RESULTS: Involving 238 participants, the study revealed a significant increase in the duration of hospitalization for those over 65 (15.8 ± 8.2 days) compared to younger groups (p < 0.001). Notably, elderly Long COVID patients exhibited a marked elevation in liver enzymes post discharge, with median ΔALT and ΔAST of 24.1 U/L and 30.2 U/L, respectively, suggesting ongoing liver injury (p < 0.001). Significant metabolic disruptions were observed, with the ΔFasting glucose showing a substantial median decrease of 21.1 mmol/L in the elderly group (p < 0.001). A pronounced reduction in ΔGGT (16.7 U/L) and ΔLDH (48.7 U/L) was noted, indicating a recovery in liver function and reduced tissue damage (p < 0.001). Coagulation profiles and liver fibrosis risk scores, particularly ΔFIB-4 and ΔAPRI, also significantly improved post discharge, indicating a reduced risk of ongoing liver complications.

CONCLUSION: This study confirms the hypothesis of more severe PASC and liver injury among the elderly Romanian population. Significant improvements post discharge suggest a degree of recovery, yet the persistent alterations in liver enzymes, glucose metabolism, and fibrosis risk scores call for continued monitoring and tailored management strategies.}, } @article {pmid38398460, year = {2024}, author = {Parzen-Johnson, S and Katz, BZ}, title = {Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection.}, journal = {Journal of clinical medicine}, volume = {13}, number = {4}, pages = {}, pmid = {38398460}, issn = {2077-0383}, abstract = {PURPOSE: This review summarizes the current scope of understanding associated with two common post-infectious complications associated with COVID-19 infection: Multi-System Inflammatory Syndrome in Children (MIS-C) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC). It identifies current gaps in the knowledge and issues that may limit the ability to fill these gaps. This review provides a framework to drive continued research.

METHODS: A comprehensive review of the current literature was performed, identifying seminal articles describing the emergence of MIS-C and PASC, and works from the literature focused on the clinical implications and pathophysiologic understanding of these disorders.

FINDINGS: Although pediatric patients experienced few severe cases of acute COVID-19 infection, the burden of disease from post-infectious sequelae is substantial. Mortality is low, but morbidity is significant. There are still numerous unknowns about the pathophysiology of both MIS-C and PASC; however, with widespread immunity developing after increased vaccination and prior infection, it may be difficult to perform adequate prospective studies to answer pathophysiologic questions. Long-term sequalae of MIS-C seem to be minimal whereas, by definition, PASC is an ongoing problem and may be severe.

IMPLICATIONS: The rapid sharing of information regarding novel conditions such as MIS-C and PASC are key to interventions related to future post-infectious sequelae outside of those stemming from COVID-19. Although MIS-C seems unlikely to return as a clinical condition in substantial numbers, there is still significant learning that can be gleaned from existing patients about general aspects of epidemiology, equity, and pathophysiology. There is significant morbidity associated with PASC and additional resources need to be dedicated to determining appropriate and effective therapies moving forward.}, } @article {pmid38398350, year = {2024}, author = {Gałczyk, M and Zalewska, A}, title = {Long COVID Symptoms vs. Back Pain and Physical Activity among Students in Poland-Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {4}, pages = {}, pmid = {38398350}, issn = {2077-0383}, abstract = {BACKGROUND: Back pain (BP) is a common condition that affects people of all ages. Moderate- and vigorous-intensity physical activity (PA) is a key element in maintaining health. The purpose of this research was to determine the level of physical activity and back pain (BP) in students with long COVID symptoms and to determine the relationship between the level of PA and BP in students with and without long COVID.

METHODS: A survey was carried out among 402 students from Poland. The inclusion criteria were as follows: student status, age of over 18 years, history of COVID-19, and consent to participate in the study. The International Physical Activity Questionnaire (IPAQ) was used to determine the level of PA. The Oswestry Disability Index (ODI) and the Neck Disability Index (NDI) were used to assess BP.

RESULTS: We found that at least half of the students surveyed did not experience any lumbosacral or cervical spine pain. The authors found no association between the level of PA in women and a history of long COVID symptoms, while there were statistically significant differences in intense PA in men (p = 0.0263), with those who did not report long COVID symptoms being more active. With regard to cervical and lumbar spine pain complaints, in our study, these were statistically significantly stronger in students who were observed to have long COVID symptoms. The difference was not significant only for lumbosacral complaints among men. No strong correlations were found between PA level and the severity of BP.

CONCLUSION: Additional investigation is required to comprehend the complex interaction between long COVID symptoms and levels of PA and BP. Special attention should be paid to the prevention of back pain mainly in the COVID-19 group of students.}, } @article {pmid38398348, year = {2024}, author = {Laguarta-Val, S and Varillas-Delgado, D and Lizcano-Álvarez, Á and Molero-Sánchez, A and Melian-Ortiz, A and Cano-de-la-Cuerda, R and Jiménez-Antona, C}, title = {Effects of Aerobic Exercise Therapy through Nordic Walking Program in Lactate Concentrations, Fatigue and Quality-of-Life in Patients with Long-COVID Syndrome: A Non-Randomized Parallel Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {13}, number = {4}, pages = {}, pmid = {38398348}, issn = {2077-0383}, abstract = {BACKGROUND: Long-COVID syndrome comprises a variety of signs and symptoms that develop during or after infection with COVID-19 which may affect the physical capabilities. However, there is a lack of studies investigating the effects of Long-COVID syndrome in sport capabilities after suffering from COVID-19 infection. The purpose of the study was to evaluate and compare lactate concentration and quality of life (QoL) in patients with Long-COVID with those who have not developed non-Long-COVID during Nordic walking exercise therapy.

METHODS: Twenty-nine patients (25.5 ± 7.1 years) took part in a non-randomized controlled trial, divided into two groups: a Long-COVID group (n = 16) and a non-Long-COVID control (n = 13). Patients were confirmed as having Long-COVID syndrome if they experienced fatigue or tiredness when performing daily activities and worsening of symptoms after vigorous physical or mental activity. All participants underwent a 12-week Nordic Walking program. Lactate concentration after exercise and distance covered during all sessions were measured. Pre- and Long-Nordic Walking program, the Modified Fatigue Impact Scale (MFIS), the Short Form 36 Health Survey (SF-36), and EURO QoL-5D (EQ-ED) were administered to assess fatigue and quality of life, respectively.

RESULTS: There was a lactate concentration effect between groups (F = 5.604; p = 0.024). However, there was no significant effect as a result of the session (F = 3.521; p = 0.121) with no interaction of group × session (F = 1.345; p = 0.414). The group main effect (F = 23.088; p < 0.001), time effect (F = 6.625; p = 0.026), and group × time (F = 4.632; p = 0.002) interaction on the SF-36 scale were noted. Also, there were a significant group main effect (F = 38.372; p < 0.001), time effect (F = 12.424; p = 0.005), and group × time interaction (F = 4.340; p = 0.014) on EQ-5D. However, there was only a significant group main effect (F = 26.235; p < 0.001) with no effect on time (F = 2.265; p = 0.160) and group × time (F = 1.584; p = 0.234) interaction on the MFIS scale.

CONCLUSIONS: The Long-COVID group showed higher lactate concentration compared with the control group during the 12 weeks of the Nordic Walking program. The Long-COVID group presented a decrease in fatigue with respect to the control group according to the MFIS scale, as well as improvement in quality of life after aerobic exercise therapy.}, } @article {pmid38397731, year = {2024}, author = {Moine, E and Molinier, V and Castanyer, A and Calvat, A and Coste, G and Vernet, A and Faugé, A and Magrina, P and Aliaga-Parera, JL and Oliver, N and Alexandre, F and Heraud, N}, title = {Safety and Efficacy of Pulmonary Rehabilitation for Long COVID Patients Experiencing Long-Lasting Symptoms.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {2}, pages = {}, pmid = {38397731}, issn = {1660-4601}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Pulmonary Disease, Chronic Obstructive/psychology ; Quality of Life ; *COVID-19 ; Dyspnea/etiology ; }, abstract = {Due to the high prevalence and persistence of long COVID, it is important to evaluate the safety and efficacy of pulmonary rehabilitation (PR) for patients who experience long-lasting symptoms more than six months after initial COVID-19 onset. Enrolled patients were admitted for a four-week in-patient-PR due to long COVID symptoms (n = 47). The safety of PR was confirmed by the absence of adverse events. Symptom-related outcomes were evaluated pre- and post-PR with significant score changes for: 6 min walking distance (61 [28 to 103] m), quality of life (mental Short Form-12: 10 [6 to 13], and physical: 9 [6 to 12]), Montreal Cognitive Assessment (1 [0 to 3]), fatigue (MFI-20: -19 [-28 to -8]), dyspnea (DYSPNEA-12: -7 [-9 to -2] and mMRC; -1 [-1 to 0]), Nijmegen questionnaire (-8 [-11 to -5]), anxiety and depression (HADS:-4 [-5 to -2] and -2 [-4 to -1], respectively) and posttraumatic stress disorder checklist scale (-8 [-12 to -4]). At the individual level, the percentage of symptomatic patients for each outcome decreased, with a high response rate, and the number of persistent symptoms per patient was reduced from six at PR initiation to three at the end of the program. Our results show that in-PR is safe and efficient at decreasing long-lasting symptoms experienced by long COVID patients at more than six months after initial disease onset.}, } @article {pmid38397678, year = {2024}, author = {Pommer, A and Halas, G and Mendis, R and Campbell, C and Semenko, B and Stadnyk, B and Thalman, L and Mair, S and Sun, Y and Johnston, N and Sanchez-Ramirez, DC}, title = {Reaching out to Patients with Long COVID to Better Understand Their Life Experiences and How to Support Their Recovery: A Patient-Oriented Knowledge Sharing Session.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {2}, pages = {}, pmid = {38397678}, issn = {1660-4601}, mesh = {Humans ; Female ; Adult ; Male ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; Life Change Events ; *COVID-19/epidemiology ; Delivery of Health Care ; }, abstract = {This article reports on participants' experiences with long COVID-19 (LC) (symptoms, impact, healthcare use, and perceived needs) and satisfaction with a patient-oriented knowledge-sharing session organized by a multidisciplinary team of healthcare professionals, researchers, and a patient partner. Twenty-six participants completed a pre-session survey. On average, they were 21 months post-COVID-19 infection (SD 10.9); 81% of them were female, and 84% were 40+ years old. The main symptoms reported included fatigue (96%), cognitive problems (92%), and general pain or discomfort (40%). More than half of the participants reported that LC has had a significant impact on their health-related quality of life. Eighty-one percent of the participants reported seeking medical help for their LC symptoms and found the services provided by physical therapists, primary care providers, and acupuncturists to be helpful in managing their condition. Participants would like to have access to healthcare providers and clinics specializing in LC. They liked the session and found the information presented useful. This information helps to better understand the experiences of people living with LC and how to support their recovery.}, } @article {pmid38397474, year = {2024}, author = {Narasaraju, T and Neeli, I and Criswell, SL and Krishnappa, A and Meng, W and Silva, V and Bila, G and Vovk, V and Serhiy, Z and Bowlin, GL and Meyer, N and Luning Prak, ET and Radic, M and Bilyy, R}, title = {Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID.}, journal = {Biomolecules}, volume = {14}, number = {2}, pages = {}, pmid = {38397474}, issn = {2218-273X}, support = {R35 HL161196/HL/NHLBI NIH HHS/United States ; UM1 AI144288/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Neutrophils/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Lung/metabolism ; Elastin ; Collagen/metabolism ; Extracellular Matrix Proteins/metabolism ; Endopeptidases ; Extracellular Matrix/metabolism ; Fibrosis ; }, abstract = {Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.}, } @article {pmid38397333, year = {2024}, author = {Schiavo, M and Di Filippo, P and Porreca, A and Prezioso, G and Orlandi, G and Rossi, N and Chiarelli, F and Attanasi, M}, title = {Potential Predictors of Long COVID in Italian Children: A Cross-Sectional Survey.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {38397333}, issn = {2227-9067}, abstract = {BACKGROUND: Identifying predictive factors of long COVID syndrome (LCS) is essential to preventing and managing this condition. We investigated the prevalence, symptoms, and risk factors of LCS in a cohort of Italian children and adolescents.

METHODS: We carried out a cross-sectional survey on demographic characteristics and clinical data related to COVID-19 phase and LCS in a cohort of children and adolescents, sending a questionnaire by using the PEDIATOTEM platform.

RESULTS: The prevalence of LCS was 25% (99/396). The most frequent symptoms of LCS included nasal congestion, diarrhea, headache, and fatigue. We found no association between demographic data (gender, age, and ethnicity) and LCS. Additionally, we showed that patients with concurrent allergic rhinitis, atopic dermatitis, respiratory disease, gastrointestinal disease, and rheumatologic disease had a higher risk of LCS than patients without those comorbidities. Patients experiencing fatigue, muscle, and abdominal pain in COVID-19 showed a higher risk of LCS than patients complaining of other symptoms. We found no association between vaccination and LCS.

CONCLUSIONS: Specific comorbidities or symptoms during acute illness were identified as being risk factors for LCS. Understanding which are the risk factors for LCS could yield a clearer picture of its pathogenesis.}, } @article {pmid38397278, year = {2024}, author = {Indolfi, C and Klain, A and Dinardo, G and D'Addio, E and Ferrara, S and Decimo, F and Ciprandi, G and Tosca, MA and Miraglia Del Giudice, M}, title = {COVID-19 Pediatric Follow-Up: Respiratory Long COVID-Associated Comorbidities and Lung Ultrasound Alterations in a Cohort of Italian Children.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {38397278}, issn = {2227-9067}, abstract = {In children, the factors that influence COVID-19 disease and its medium- and long-term effects are little known. Our investigation sought to evaluate the presence of comorbidity factors associated with respiratory long COVID manifestations in children and to study ultrasound abnormalities following SARS-CoV-2 infection. Children, who arrived at the 'Respiratory Diseases of Pediatric Interest Unit' at the Department of Woman, Child, and General and Specialized Surgery of the University of Campania 'Luigi Vanvitelli', were selected during the timeframe from September 2021 to October 2022. The children were diagnosed with a SARS-CoV-2 infection that occurred at least one month before the visit. All patients followed a COVID-19 follow-up protocol, developed by the Italian Society of Pediatric Respiratory Diseases (SIMRI), which included: collection of data regarding SARS-CoV-2 illness and history of known respiratory and allergic diseases; physical examination; BMI assessment; baseline spirometry and after bronchodilation test; six-minute walking test; and lung ultrasound (LUS). In a cohort of 104 participants with respiratory long COVID symptoms (64.7% male, average age 8.92 years), 46.1% had fever with other symptoms, and 1% required hospitalization. BMI analysis showed 58.4% of the cohort was overweight. The LUS was positive in 27.0% of cases. A significant BMI association was observed with COVID-19 symptoms and LUS score (p-value < 0.05). No associations were found with asthma or atopy.}, } @article {pmid38396973, year = {2024}, author = {Nakane, S and Koike, H and Hayashi, T and Nakatsuji, Y}, title = {Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396973}, issn = {1422-0067}, support = {22FC1007//Ministry of Health Labour and Welfare/ ; }, mesh = {Humans ; Ganglia, Autonomic ; Post-Acute COVID-19 Syndrome ; *Autoimmune Diseases of the Nervous System ; Autonomic Nervous System ; *Autonomic Nervous System Diseases/diagnosis/etiology ; *Autoimmune Diseases/diagnosis/pathology ; *Peripheral Nervous System Diseases/pathology ; Autoantibodies ; }, abstract = {Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.}, } @article {pmid38396274, year = {2024}, author = {Williams, MK and Crawford, CA and Zapolski, TC and Hirsh, AT and Stewart, JC}, title = {Longer-Term Mental Health Consequences of COVID-19 Infection: Moderation by Race and Socioeconomic Status.}, journal = {International journal of behavioral medicine}, volume = {}, number = {}, pages = {}, pmid = {38396274}, issn = {1532-7558}, abstract = {OBJECTIVE: While evidence suggests that the mental health symptoms of COVID-19 can persist for several months following infection, little is known about the longer-term mental health effects and whether certain sociodemographic groups may be particularly impacted. This cross-sectional study aimed to characterize the longer-term mental health consequences of COVID-19 infection and examine whether such consequences are more pronounced in Black people and people with lower socioeconomic status.

METHODS: 277 Black and White adults (age ≥ 30 years) with a history of COVID-19 (tested positive ≥ 6 months prior to participation) or no history of COVID-19 infection completed a 45-minute online questionnaire battery.

RESULTS: People with a history of COVID-19 had greater depressive (d = 0.24), anxiety (d = 0.34), post-traumatic stress disorder (PTSD) (d = 0.32), and insomnia (d = 0.31) symptoms than those without a history of COVID-19. These differences remained for anxiety, PTSD, and insomnia symptoms after adjusting for age, sex, race, education, income, employment status, body mass index, and smoking status. No differences were detected for perceived stress and general psychopathology. People with a history of COVID-19 had more than double the odds of clinically significant symptoms of anxiety (OR = 2.22) and PTSD (OR = 2.40). Education, but not race, income, or employment status, moderated relationships of interest such that COVID-19 status was more strongly and positively associated with all the mental health outcomes for those with fewer years of education.

CONCLUSION: The mental health consequences of COVID-19 may be significant, widespread, and persistent for at least 6 months post-infection and may increase as years of education decreases.}, } @article {pmid38395459, year = {2024}, author = {Ito, F and Terai, H and Kondo, M and Takemura, R and Namkoong, H and Asakura, T and Chubachi, S and Masuzawa, K and Nakayama, S and Suzuki, Y and Hashiguchi, M and Kagyo, J and Shiomi, T and Minematsu, N and Manabe, T and Fukui, T and Funatsu, Y and Koh, H and Masaki, K and Ohgino, K and Miyata, J and Kawada, I and Ishii, M and Sato, Y and Fukunaga, K}, title = {Cluster analysis of long COVID in Japan and association of its trajectory of symptoms and quality of life.}, journal = {BMJ open respiratory research}, volume = {11}, number = {1}, pages = {}, pmid = {38395459}, issn = {2052-4439}, mesh = {Aged ; Humans ; Female ; Adolescent ; Adult ; *COVID-19/epidemiology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Japan/epidemiology ; Prospective Studies ; Cluster Analysis ; Fatigue ; Dyspnea/epidemiology/etiology/therapy ; Cough ; }, abstract = {BACKGROUND: Multiple prolonged symptoms observed in patients who recovered from COVID-19 are defined as long COVID. Although diverse phenotypic combinations are possible, they remain unclear. This study aimed to perform a cluster analysis of long COVID in Japan and clarify the association between its characteristics and background factors and quality of life (QOL).

METHODS: This multicentre prospective cohort study collected various symptoms and QOL after COVID-19 from January 2020 to February 2021. This study included 935 patients aged ≥18 years with COVID-19 at 26 participating medical facilities. Hierarchical cluster analysis was performed using 24 long COVID symptom at 3 months after diagnosis.

RESULTS: Participants were divided into the following five clusters: numerous symptoms across multiple organs (cluster 1, n=54); no or minor symptoms (cluster 2, n=546); taste and olfactory disorders (cluster 3, n=76); fatigue, psychoneurotic symptoms and dyspnoea (low prevalence of cough and sputum) (cluster 4, n=207) and fatigue and dyspnoea (high prevalence of cough and sputum) (cluster 5, n=52). Cluster 1 included elderly patients with severe symptoms, while cluster 3 included young female with mild symptoms. No significant differences were observed in the comorbidities. Cluster 1 showed the most impaired QOL, followed by clusters 4 and 5; these changes as well as the composition of symptoms were observed over 1 year.

CONCLUSIONS: We identified patients with long COVID with diverse characteristics into five clusters. Future analysis of these different pathologies could result in individualised treatment of long COVID.

TRIAL REGISTRATION NUMBER: The study protocol is registered at UMIN clinical trials registry (UMIN000042299).}, } @article {pmid38394160, year = {2024}, author = {Solomou, I and Nikolaou, F and Michaelides, MP and Constantinidou, F}, title = {Long-term psychological impact of the pandemic COVID-19: Identification of high-risk groups and assessment of precautionary measures five months after the first wave of restrictions was lifted.}, journal = {PLOS global public health}, volume = {4}, number = {2}, pages = {e0002847}, pmid = {38394160}, issn = {2767-3375}, abstract = {Critical facets of our lives have been disrupted by the COVID-19 outbreak for almost three years. During this time, there has been a lot of clinical and research interest in issues related to mental health. However, few have examined the pandemic's long-term psychological effects. The aims of the present study were to assess the long-term psychological impact of the pandemic COVID -19, five months after the first wave restriction measures were lifted, to identify high-risk groups and to address the use of precautionary measures (PM). Information about sociodemographic characteristics, mental health, coping mechanisms, and compliance with precautionary measures (PM) were all gathered in Cyprus through an anonymous online survey. The poll was completed by 1128 people (73% of whom were female). For the purposes of the present study, descriptive statistics and structural equation modeling were used. 32.3% of participants experienced moderate-to-severe anxiety symptoms, where 16.4% and 23% reported moderate-to-severe depression and post-traumatic stress symptoms respectively. Lower levels of anxiety, depression, and post-traumatic stress symptoms as well as greater compliance to PM were linked to higher levels of resilience. Additionally, subgroups of participants, at a higher risk for negative psychological effects were identified, such as women and young adults. Our findings demonstrate the long-lasting effects of the COVID-19 pandemic on mental health and provide guidance on how to deal with similar situations. It also raises questions about the concurrent effects on people with the long COVID syndrome.}, } @article {pmid38393535, year = {2024}, author = {Pszczołowska, M and Walczak, K and Misków, W and Antosz, K and Batko, J and Karska, J and Leszek, J}, title = {Molecular cross-talk between long COVID-19 and Alzheimer's disease.}, journal = {GeroScience}, volume = {46}, number = {3}, pages = {2885-2899}, pmid = {38393535}, issn = {2509-2723}, mesh = {Humans ; *Alzheimer Disease/metabolism ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Amyloid beta-Peptides ; Chronic Disease ; }, abstract = {The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.}, } @article {pmid38393135, year = {2024}, author = {Aguilar-Martinez, SL and Sandoval-Peña, GA and Molina-Mora, JA and Tsukayama-Cisneros, P and Díaz-Vélez, C and Aguilar-Gamboa, FR and Bonilla-Aldana, DK and Rodriguez-Morales, AJ}, title = {Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru.}, journal = {Tropical medicine and infectious disease}, volume = {9}, number = {2}, pages = {}, pmid = {38393135}, issn = {2414-6366}, abstract = {OBJECTIVE: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru.

METHODS: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq[®]. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12.

RESULTS: It was determined that during the period from December 2020 to January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, and B.1.111 circulated, with lineage C.14 being the most predominant at 76.7% (n = 23/30). These lineages were classified in clade 20D mainly and also within clades 20B and 20A. On the contrary, the variants found in the second batch of samples of the period from September to October 2021 were Delta (72.7%), Gamma (13.6%), Mu (4.6%), and Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J, and 21I.

CONCLUSIONS: This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology.}, } @article {pmid38393096, year = {2024}, author = {Nederlof, RA and de la Garza, MA and Bakker, J}, title = {Perspectives on SARS-CoV-2 Cases in Zoological Institutions.}, journal = {Veterinary sciences}, volume = {11}, number = {2}, pages = {}, pmid = {38393096}, issn = {2306-7381}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a zoological institution were initially reported in March 2020. Since then, at least 94 peer-reviewed cases have been reported in zoos worldwide. Among the affected animals, nonhuman primates, carnivores, and artiodactyls appear to be most susceptible to infection, with the Felidae family accounting for the largest number of reported cases. Clinical symptoms tend to be mild across taxa; although, certain species exhibit increased susceptibility to disease. A variety of diagnostic tools are available, allowing for initial diagnostics and for the monitoring of infectious risk. Whilst supportive therapy proves sufficient in most cases, monoclonal antibody therapy has emerged as a promising additional treatment option. Effective transmission of SARS-CoV-2 in some species raises concerns over potential spillover and the formation of reservoirs. The occurrence of SARS-CoV-2 in a variety of animal species may contribute to the emergence of variants of concern due to altered viral evolutionary constraints. Consequently, this review emphasizes the need for effective biosecurity measures and surveillance strategies to prevent and control SARS-CoV-2 infections in zoological institutions.}, } @article {pmid38392604, year = {2024}, author = {Kell, DB and Khan, MA and Kane, B and Lip, GYH and Pretorius, E}, title = {Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID.}, journal = {Journal of personalized medicine}, volume = {14}, number = {2}, pages = {}, pmid = {38392604}, issn = {2075-4426}, support = {142142//National Research Foundation/ ; NNF10CC1016517//Novo Nordisk Foundation/ ; SIR grant//South African Medical Research Council/ ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of a variety of chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block the flow of blood through microcapillaries and thus cause tissue hypoxia, are not simply correlated with but in fact, by preceding it, may be a chief intermediary cause of POTS, in which tachycardia is simply the body's exaggerated 'physiological' response to hypoxia. Similar reasoning accounts for the symptoms bundled under the term 'fatigue'. Amyloids are known to be membrane disruptors, and when their targets are nerve membranes, this can explain neurotoxicity and hence the autonomic nervous system dysfunction that contributes to POTS. Taken together as a system view, we indicate that fibrinaloid microclots can serve to link POTS and fatigue in long COVID in a manner that is at once both mechanistic and explanatory. This has clear implications for the treatment of such diseases.}, } @article {pmid38392595, year = {2024}, author = {Matthaiou, AM and Bizymi, N and Pagonidis, K and Manousaki, E and Fragkoulakis, M and Lambiri, I and Mitrouska, I and Vasarmidi, E and Tzanakis, N and Antoniou, KM}, title = {Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease.}, journal = {Journal of personalized medicine}, volume = {14}, number = {2}, pages = {}, pmid = {38392595}, issn = {2075-4426}, abstract = {Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.}, } @article {pmid38392036, year = {2024}, author = {Taieb, A and Nassim, BHS and Asma, G and Jabeur, M and Ghada, S and Asma, BA}, title = {The Growing Understanding of the Pituitary Implication in the Pathogenesis of Long COVID-19 Syndrome: A Narrative Review.}, journal = {Advances in respiratory medicine}, volume = {92}, number = {1}, pages = {96-109}, pmid = {38392036}, issn = {2543-6031}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Pituitary Gland ; Fatigue/etiology ; }, abstract = {Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection, is a condition where individuals who have recovered from the acute phase of COVID-19 continue to experience a range of symptoms for weeks or even months afterward. While it was initially thought to primarily affect the respiratory system, it has become clear that Long COVID-19 can involve various organs and systems, including the endocrine system, which includes the pituitary gland. In the context of Long COVID-19, there is a growing understanding of the potential implications for the pituitary gland. The virus can directly affect the pituitary gland, leading to abnormalities in hormone production and regulation. This can result in symptoms such as fatigue, changes in appetite, and mood disturbances. Long COVID-19, the persistent and often debilitating condition following acute COVID-19 infection, may be explained by deficiencies in ACTH and Growth hormone production from the pituitary gland. Corticotropin insufficiency can result in the dysregulation of the body's stress response and can lead to prolonged feelings of stress, fatigue, and mood disturbances in Long COVID-19 patients. Simultaneously, somatotropin insufficiency can affect growth, muscle function, and energy metabolism, potentially causing symptoms such as muscle weakness, exercise intolerance, and changes in body composition. Recently, some authors have suggested the involvement of the pituitary gland in Post COVID-19 Syndrome. The exact mechanisms of viral action on infected cells remain under discussion, but inflammatory and autoimmune mechanisms are primarily implicated. The aim of our study will be to review the main pituitary complications following COVID-19 infection. Moreover, we will explain the possible involvement of the pituitary gland in the persistence of Post COVID-19 Syndrome.}, } @article {pmid38391826, year = {2024}, author = {Daniels, K and Mourad, J and Bonnechère, B}, title = {Exploring the Use of Mobile Health for the Rehabilitation of Long COVID Patients: A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {38391826}, issn = {2227-9032}, abstract = {The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes; however, more research is needed to strengthen the existing evidence base, as one of the most important limitations is the limited number of trials and the evaluation of varied therapies. This analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve the comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.}, } @article {pmid38391754, year = {2024}, author = {Leão Batista Simões, J and Webler Eichler, S and Raitz Siqueira, ML and de Carvalho Braga, G and Bagatini, MD}, title = {Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391754}, issn = {2076-3425}, support = {Proj. No 404256/2021-0 and 310606/2021-7).//National Council for Scientific and Technological Development/ ; }, abstract = {Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.}, } @article {pmid38391717, year = {2024}, author = {Zou, L and Mahmut, MK}, title = {Investigating the Interplay between Olfaction, Social Behaviour, and Individual Differences: Editorial.}, journal = {Brain sciences}, volume = {14}, number = {2}, pages = {}, pmid = {38391717}, issn = {2076-3425}, abstract = {Long-COVID mercilessly brought awareness to what olfaction researchers have known all along; losing your sense of smell changes your experiences with the world around you and can compromise your health and wellbeing [...].}, } @article {pmid38390594, year = {2024}, author = {Adler, BL and Chung, T and Rowe, PC and Aucott, J}, title = {Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1344862}, pmid = {38390594}, issn = {1664-2295}, abstract = {Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.}, } @article {pmid38389299, year = {2024}, author = {Martínez-Pozas, O and Meléndez-Oliva, E and Rolando, LM and Rico, JAQ and Corbellini, C and Sánchez Romero, EA}, title = {The pulmonary rehabilitation effect on long covid-19 syndrome: A systematic review and meta-analysis.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {29}, number = {2}, pages = {e2077}, doi = {10.1002/pri.2077}, pmid = {38389299}, issn = {1471-2865}, support = {//Award for Best Research Project in post-COVID-19 sequelae/ ; //the Ilustre Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid, December 2021/ ; }, mesh = {Adult ; Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue ; Dyspnea ; }, abstract = {OBJECTIVES: This systematic review and meta-analysis aims to evaluate the efficacy of pulmonary rehabilitation (PR) in improving dyspnea, fatigue, physical activity, quality of life, anxiety and depression in patients with Long COVID-19 (LC). The impact of PR on LC and a comparison of face-to-face and telerehabilitation approaches was explored.

METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO. A literature search included PubMed, Web of Science, and Cochrane Library until January 2023. No language filters were applied. Randomized controlled trials, non-randomized controlled trials, and observational studies were included. The risk of bias was assessed using appropriate tools. Descriptive analysis and meta-analysis were performed. Forest plots presented results. Statistical analyses were conducted using the Metafor Package in R v.3.4.2.

RESULTS/FINDINGS: This systematic review and meta-analysis included 16 studies on PR in LC patients. A total of 1027 adults were included. The studies varied in design, with seven observational studies, three quasi-experimental studies, and six randomized controlled trials. Dyspnea, physical function, quality of life, psychological state, and fatigue were assessed as outcomes. The review found that pulmonary rehabilitation had a significant positive effect on dyspnea, physical function, quality of life (both global and physical domain), anxiety, and depression. However, the effect on fatigue was not significant. Heterogeneity was observed in some analyses, and publication bias was found in certain outcomes. Age and study design were identified as potential moderators. Both face-to-face and telerehabilitation interventions improved the studied outcomes, with only differences in the physical domain of quality of life favoring the face-to-face group.

PR improved dyspnea, physical function, quality of life, and psychological state in LC patients, but not fatigue. Face-to-face and telerehabilitation have similar effects, except for physical quality of life.}, } @article {pmid38388910, year = {2024}, author = {Cohen, J and Rodgers, YVM}, title = {Long COVID Prevalence, Disability, and Accommodations: Analysis Across Demographic Groups.}, journal = {Journal of occupational rehabilitation}, volume = {34}, number = {2}, pages = {335-349}, pmid = {38388910}, issn = {1573-3688}, support = {90RTEM0006/ACL/ACL HHS/United States ; 90RTEM0006-01-00//National Institute on Disability, Independent Living, and Rehabilitation Research/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Disabled Persons/statistics & numerical data ; Male ; Adult ; Prevalence ; Middle Aged ; United States/epidemiology ; SARS-CoV-2 ; Teleworking/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Young Adult ; Adolescent ; Aged ; }, abstract = {PURPOSE: This paper examines the prevalence of long COVID across different demographic groups in the US and the extent to which workers with impairments associated with long COVID have engaged in pandemic-related remote work.

METHODS: We use the US Household Pulse Survey to evaluate the proportion of all adults who self-reported to (1) have had long COVID, and (2) have activity limitations due to long COVID. We also use data from the US Current Population Survey to estimate linear probability regressions for the likelihood of pandemic-related remote work among workers with and without disabilities.

RESULTS: Findings indicate that women, Hispanic people, sexual and gender minorities, individuals without 4-year college degrees, and people with preexisting disabilities are more likely to have long COVID and to have activity limitations from long COVID. Remote work is a reasonable arrangement for people with such activity limitations and may be an unintentional accommodation for some people who have undisclosed disabilities. However, this study shows that people with disabilities were less likely than people without disabilities to perform pandemic-related remote work.

CONCLUSION: The data suggest this disparity persists because people with disabilities are clustered in jobs that are not amenable to remote work. Employers need to consider other accommodations, especially shorter workdays and flexible scheduling, to hire and retain employees who are struggling with the impacts of long COVID.}, } @article {pmid38388737, year = {2024}, author = {}, title = {Leaky blood-brain barrier in long-COVID-associated brain fog.}, journal = {Nature neuroscience}, volume = {27}, number = {3}, pages = {395-396}, pmid = {38388737}, issn = {1546-1726}, mesh = {Humans ; *Blood-Brain Barrier ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Brain ; Mental Fatigue ; }, } @article {pmid38388736, year = {2024}, author = {Greene, C and Connolly, R and Brennan, D and Laffan, A and O'Keeffe, E and Zaporojan, L and O'Callaghan, J and Thomson, B and Connolly, E and Argue, R and Meaney, JFM and Martin-Loeches, I and Long, A and Cheallaigh, CN and Conlon, N and Doherty, CP and Campbell, M}, title = {Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.}, journal = {Nature neuroscience}, volume = {27}, number = {3}, pages = {421-432}, pmid = {38388736}, issn = {1546-1726}, support = {20/COV/0312//Science Foundation Ireland (SFI)/ ; 21/SPP/3732//Science Foundation Ireland (SFI)/ ; }, mesh = {Humans ; Blood-Brain Barrier/metabolism ; Post-Acute COVID-19 Syndrome ; Endothelial Cells/metabolism ; Leukocytes, Mononuclear ; *COVID-19/complications ; *Cognitive Dysfunction/pathology ; Inflammation/pathology ; Mental Fatigue/metabolism/pathology ; }, abstract = {Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.}, } @article {pmid38387538, year = {2024}, author = {Hejazian, SS and Sadr, AV and Shahjouei, S and Vemuri, A and Abedi, V and Zand, R}, title = {Prevalence and Determinants of Long-Term Post-COVID Conditions in the United States: 2022 Behavioral Risk Factor Surveillance System.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.02.010}, pmid = {38387538}, issn = {1555-7162}, abstract = {BACKGROUND: A significant proportion of COVID survivors experience lingering and debilitating symptoms following acute COVID-19 infection. According to the national research plan on long COVID, it is a national priority to identify the prevalence of post-COVID conditions and their associated factors.

METHOD: We performed a cross-sectional analysis of the Prevention Behavioral Risk Factor Surveillance System (BRFSS) 2022, the largest continuously gathered health survey dataset worldwide by the Centers for Disease Control. After identifying individuals with a positive history of COVID-19, we grouped COVID-19 survivors based on whether they experienced long-term post-COVID conditions. Using survey-specific R packages, we compared the two groups' socio-demographics, comorbidities, and lifestyle-related factors. A logistic regression model was used to identify factors associated with post-COVID conditions.

RESULTS: The overall estimated prevalence of long-term post-COVID conditions among COVID survivors was 21.7%. Fatigue (5.7%), dyspnea (4.2%), and anosmia/ageusia (3.8%) were the most frequent symptoms. Based on multivariate logistic regression analysis, female sex, body mass index (BMI)≥25, lack of insurance, history of pulmonary disease, depression, and arthritis, being a former smoker, and sleep duration <7 h/d were associated with higher odds of post-COVID conditions. On the other hand, age >64 y/o, Black race, and annual household income ≥$100k were associated with lower odds of post-COVID conditions.

CONCLUSION: Our findings indicate a notable prevalence of post-COVID conditions, particularly among middle-aged women and individuals with comorbidities or adverse lifestyles. This high-risk demographic may require long-term follow-up and support. Further investigations are essential to facilitate the development of specified healthcare and therapeutic strategies for those suffering from post-COVID conditions.}, } @article {pmid38387405, year = {2024}, author = {Gu, X and Wong, CCL and Cao, B}, title = {Authors' reply to Letter regarding "Probing Long COVID through a Proteomic Lens: a Comprehensive Two-Year Longitudinal Cohort Study of Hospitalised Survivor".}, journal = {EBioMedicine}, volume = {101}, number = {}, pages = {105029}, pmid = {38387405}, issn = {2352-3964}, mesh = {Humans ; *COVID-19 ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Proteomics ; Cohort Studies ; }, } @article {pmid38386747, year = {2024}, author = {Al-Aly, Z and Topol, E}, title = {Solving the puzzle of Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6685}, pages = {830-832}, doi = {10.1126/science.adl0867}, pmid = {38386747}, issn = {1095-9203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/epidemiology ; Chronic Disease ; Male ; Female ; Child ; Adult ; }, abstract = {Long Covid provides an opportunity to understand how acute infections cause chronic disease.}, } @article {pmid38386633, year = {2024}, author = {León-Herrera, S and Samper-Pardo, M and Oliván-Blázquez, B and Sánchez-Recio, R and Magallón-Botaya, R and Sánchez-Arizcuren, R}, title = {Loss of socioemotional and occupational roles in individuals with Long COVID according to sociodemographic and clinical factors: Secondary data from a randomized clinical trial.}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0296041}, pmid = {38386633}, issn = {1932-6203}, mesh = {Adult ; Humans ; Middle Aged ; COVID-19/economics/epidemiology ; Cross-Sectional Studies ; Employment ; *Post-Acute COVID-19 Syndrome/economics/epidemiology ; Quality of Life ; SARS-CoV-2 ; Socioeconomic Factors ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Long COVID syndrome can have a major impact on life organization. Its persistent symptoms may cause a potentially disabling condition that affects the quality of life of those suffering from it. The resulting loss of functional independence hinders the ability to return to normal life. Many research studies carried out on this novel syndrome have focused on describing its extensive symptomatology. Studies on later repercussions, however, such as disability or loss of significant roles, remain scarce. This study examines the loss of socioemotional and occupational roles experienced by individuals suffering from Long COVID, as a result of the disease. A secondary objective is to analyze the sociodemographic and clinical factors associated with this loss of roles.

PATIENTS AND METHODS: A cross-sectional study was conducted with the participation of 100 patients diagnosed with Long COVID, over the age of 18, and attended by Primary Health Care in the Autonomous Community of Aragon. The main study variable was the loss of significant socioemotional and occupational roles by the participants. Sociodemographic and clinical data were also collected through a structured interview. Subsequently, a descriptive, correlational, and regression-based statistical analysis was performed using the SPSS Statistics program.

RESULTS: Based on the 100 study participants, the median number of roles lost was 3 (IQR 2) and the median number of valuable roles lost was 2 (IQR 2). More cognitive impairment and not having an active work role were predictors of a greater loss of valuables roles.

CONCLUSION: Long COVID symptoms hinder the development of socioemotional and occupational roles. Healthcare professionals should consider this when intervening to ensure that their patients may recover their life as it was before the disease.}, } @article {pmid38385713, year = {2024}, author = {Miranda, GASC and Corrêa, IA and Amorim, ÉA and Caldas, LA and Carneiro, FÁ and da Costa, LJ and Granjeiro, JM and Tanuri, A and de Souza, W and Baptista, LS}, title = {Cost-effective 3D lung tissue spheroid as a model for SARS-CoV-2 infection and drug screening.}, journal = {Artificial organs}, volume = {48}, number = {7}, pages = {723-733}, doi = {10.1111/aor.14729}, pmid = {38385713}, issn = {1525-1594}, support = {//Financiadora de Estudos e Projetos/ ; //Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; }, mesh = {Humans ; *Spheroids, Cellular/virology ; *COVID-19/virology ; *SARS-CoV-2/physiology ; *Lung/virology/pathology ; *Drug Evaluation, Preclinical ; COVID-19 Drug Treatment ; Antiviral Agents/pharmacology/therapeutic use ; Coculture Techniques ; Cytokines/metabolism ; Cost-Benefit Analysis ; Epithelial Cells/virology ; }, abstract = {BACKGROUND: The SARS-CoV-2 pandemic has spurred an unparalleled scientific endeavor to elucidate the virus' structure, infection mechanisms, and pathogenesis. Two-dimensional culture systems have been instrumental in shedding light on numerous aspects of COVID-19. However, these in vitro systems lack the physiological complexity to comprehend the infection process and explore treatment options. Three-dimensional (3D) models have been proposed to fill the gap between 2D cultures and in vivo studies. Specifically, spheroids, composed of lung cell types, have been suggested for studying SARS-CoV-2 infection and serving as a drug screening platform.

METHODS: 3D lung spheroids were prepared by coculturing human alveolar or bronchial epithelial cells with human lung stromal cells. The morphology, size, and ultrastructure of spheroids before and after SARS-CoV-2 infection were analyzed using optical and electron microscopy. Immunohistochemistry was used to detect spike protein and, thus, the virus presence in the spheroids. Multiplex analysis elucidated the cytokine release after virus infection.

RESULTS: The spheroids were stable and kept their size and morphology after SARS-CoV-2 infection despite the presence of multivesicular bodies, endoplasmic reticulum rearrangement, tubular compartment-enclosed vesicles, and the accumulation of viral particles. The spheroid responded to the infection releasing IL-6 and IL-8 cytokines.

CONCLUSION: This study demonstrates that coculture spheroids of epithelial and stromal cells can serve as a cost-effective infection model for the SARS-CoV-2 virus. We suggest using this 3D spheroid as a drug screening platform to explore new treatments related to the cytokines released during virus infection, especially for long COVID treatment.}, } @article {pmid38384879, year = {2024}, author = {Rybkina, J and Jacob, N and Colella, B and Gold, D and Stewart, DE and Ruttan, LA and Meusel, LC and McAndrews, MP and Abbey, S and Green, R}, title = {Self-managing symptoms of Long COVID: an education and strategies research protocol.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1106578}, pmid = {38384879}, issn = {2296-2565}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Self-Management ; Quality of Life ; SARS-CoV-2 ; *COVID-19 ; Disease Progression ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {Post-acute sequelae of SARS-COV-2 (PASC) is growing in prevalence, and involves symptoms originating from the central neurological, cardiovascular, respiratory, gastrointestinal, autonomic nervous, or immune systems. There are non-specific symptoms such as fatigue, headaches, and brain fog, which cannot be ascribed to a single system. PASC places a notable strain on our healthcare system, which is already laden with a large number of acute-COVID-19 patients. Furthermore, it impedes social, academic and vocational functioning, and impacts family life, relationships, and work/financial life. The treatment for PASC needs to target this non-specific etiology and wide-ranging sequelae. In conditions similar to PASC, such as "chemo brain," and prolonged symptoms of concussion, the non-specific symptoms have shown to be effectively managed through education and strategies for self-management and Mindfulness interventions. However, such interventions have yet to be empirically evaluated in PASC to our knowledge. In response to this gap, we have developed a virtual education intervention synthesized by psychiatrists and clinical psychologists for the current study. We will undertake a two-phase randomized controlled trial to determine the feasibility (Phase 1; N = 90) and efficacy (Phase 2; sample sized based on phase 1 results) of the novel 8 week Education and Self-Management Strategies group compared to a mindfulness skills program, both delivered virtually. Main outcomes include confidence/ability to self-manage symptoms, quality of life, and healthcare utilization. This study stands to mitigate the deleterious intrusiveness of symptoms on everyday life in patients with PASC, and may also help to reduce the impact of PASC on the healthcare system. Clinical trial registration:https://classic.clinicaltrials.gov/ct2/show/NCT05268523; identifier NCT05268523.}, } @article {pmid38384747, year = {2024}, author = {Lammers, N and Beese, F and Hoebel, J and Poethko-Müller, C and Wachtler, B}, title = {Social Inequalities in Long-Term Health Effects After COVID-19-A Scoping Review.}, journal = {International journal of public health}, volume = {69}, number = {}, pages = {1606739}, pmid = {38384747}, issn = {1661-8564}, mesh = {Humans ; *COVID-19/epidemiology ; *Socioeconomic Factors ; *SARS-CoV-2 ; Health Status Disparities ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objectives: We aimed to map and synthesize evidence about social inequalities in long-term health effects after COVID-19 (LTHE), often referred to as "long COVID" or "post-COVID-19 conditions." Methods: We conducted a scoping review of peer-reviewed articles by searching the databases Embase and Scopus. According to predefined inclusion criteria, titles/abstracts and full texts were screened for eligibility. Additionally, reference lists of all included studies were hand-searched for eligible studies. This study followed the PRISMA guidelines for scoping reviews. Results: Nineteen articles were included. LTHE were analysed according to ethnicity, education, income, employment and deprivation indices. The studies varied significantly in their definitions of LTHE. Eighty-two analyses showed no statistically significant associations. At least 12 studies had a high risk of type II errors. Only studies associating deprivation indices and long COVID tended to show a higher prevalence of LTHE in deprived areas. Conclusion: Although some studies indicated social inequalities in LTHE, evidence was generally weak and inconclusive. Further studies with larger sample sizes specifically designed to detect social inequalities regarding LTHE are needed to inform future healthcare planning and public health policies.}, } @article {pmid38383883, year = {2024}, author = {Ose, DJ and Gardner, E and Millar, M and Curtin, A and Wu, J and Zhang, M and Schaefer, C and Wang, J and Leiser, J and Stoesser, K and Kiraly, B}, title = {A cross-sectional and population-based study from primary care on post-COVID-19 conditions in non-hospitalized patients.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {24}, pmid = {38383883}, issn = {2730-664X}, support = {UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Current research on post-COVID-19 conditions (PCC) has focused on hospitalized COVID-19 patients, and often lacks a comparison group. This study assessed the prevalence of PCC in non-hospitalized COVID-19 primary care patients compared to primary care patients not diagnosed with COVID-19.

METHODS: This cross-sectional, population-based study (n = 2539) analyzed and compared the prevalence of PCC in patients with a positive COVID-19 test (n = 1410) and patients with a negative COVID-19 test (n = 1129) never hospitalized for COVID-19 related conditions. Participants were identified using electronic health records and completed an electronic questionnaire, available in English and Spanish, including 54 potential post COVID-19 symptoms. Logistic regression was conducted to assess the association of PCC with COVID-19.

RESULTS: Post-COVID-19 conditions are prevalent in both groups, and significantly more prevalent in patients with COVID-19. Strong significant differences exist for the twenty most reported conditions, except for anxiety. Common conditions are fatigue (59.5% (COVID-19 positive) vs. 41.3% (COVID-19 negative); OR 2.15 [1.79-2.60]), difficulty sleeping (52.1% (positive) vs. 41.9% (negative); OR 1.42 [1.18-1.71]) and concentration problems (50.6% (positive) vs 28.5% (negative); OR 2.64 [2.17-3.22]). Similar disparities in prevalence are also observed after comparing two groups (positive vs. negative) by age, sex, time since testing, and race/ethnicity.

CONCLUSIONS: PCC is highly prevalent in non-hospitalized COVID-19 patients in primary care. However, it is important to note that PCC strongly overlaps with common health symptoms seen in primary care, including fatigue, difficulty sleeping, and headaches, which makes the diagnosis of PCC in primary care even more challenging.}, } @article {pmid38383783, year = {2024}, author = {Ghafari, M and Hall, M and Golubchik, T and Ayoubkhani, D and House, T and MacIntyre-Cockett, G and Fryer, HR and Thomson, L and Nurtay, A and Kemp, SA and Ferretti, L and Buck, D and Green, A and Trebes, A and Piazza, P and Lonie, LJ and Studley, R and Rourke, E and Smith, DL and Bashton, M and Nelson, A and Crown, M and McCann, C and Young, GR and Santos, RAND and Richards, Z and Tariq, MA and Cahuantzi, R and , and , and , and Barrett, J and Fraser, C and Bonsall, D and Walker, AS and Lythgoe, K}, title = {Prevalence of persistent SARS-CoV-2 in a large community surveillance study.}, journal = {Nature}, volume = {626}, number = {8001}, pages = {1094-1101}, pmid = {38383783}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_19027/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Amino Acid Substitution ; Antibodies, Monoclonal/immunology ; *COVID-19/epidemiology/virology ; Evolution, Molecular ; *Health Surveys ; Immunocompromised Host/immunology ; Mutation ; *Persistent Infection/epidemiology/virology ; Post-Acute COVID-19 Syndrome/epidemiology/virology ; Prevalence ; RNA, Viral/analysis/genetics ; *SARS-CoV-2/chemistry/classification/genetics/immunology/isolation & purification ; Selection, Genetic ; Self Report ; Time Factors ; Viral Load ; Virus Replication ; }, abstract = {Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks[1-5], give rise to highly divergent lineages[6-8] and contribute to cases with post-acute COVID-19 sequelae (long COVID)[9,10]. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people[11-14]. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.}, } @article {pmid38383493, year = {2024}, author = {Cornelissen, MEB and Bloemsma, LD and Vaes, AW and Baalbaki, N and Deng, Q and Beijers, RJHCG and Noij, LCE and Houweling, L and Bazdar, S and Spruit, MA and Maitland-van der Zee, AH and , }, title = {Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {191}, pmid = {38383493}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/complications/epidemiology/diagnosis ; Prospective Studies ; *COVID-19/complications ; SARS-CoV-2 ; Cohort Studies ; }, abstract = {BACKGROUND: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort.

METHODS: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found.

RESULTS: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients.

CONCLUSIONS: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.}, } @article {pmid38383157, year = {2024}, author = {Steinruecke, M and Mason, I and Keen, M and McWhirter, L and Carson, AJ and Stone, J and Hoeritzauer, I}, title = {Pain and functional neurological disorder: a systematic review and meta-analysis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {95}, number = {9}, pages = {874-885}, pmid = {38383157}, issn = {1468-330X}, mesh = {Humans ; *Nervous System Diseases/complications ; *Chronic Pain ; }, abstract = {BACKGROUND: Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the clinical features of chronic pain in people with FND, and of FND in people with chronic pain, have not been comprehensively studied.

METHODS: We systematically reviewed PubMed, Embase and PsycINFO for studies of chronic pain in adults with FND and FND in patients with chronic pain. We described the proportions of patients reporting pain, pain rating and timing, pain-related diagnoses and responsiveness to treatment. We performed random effects meta-analyses of the proportions of patients with FND who reported pain or were diagnosed with pain-related disorders.

RESULTS: Seven hundred and fifteen articles were screened and 64 were included in the analysis. Eight case-control studies of 3476 patients described pain symptoms in a higher proportion of patients with FND than controls with other neurological disorders. A random effects model of 30 cohorts found that an estimated 55% (95% CI 46% to 64%) of 4272 patients with FND reported pain. Random effects models estimated diagnoses of complex regional pain syndrome in 22% (95% CI 6% to 39%) of patients, irritable bowel syndrome in 16% (95% CI 9% to 24%) and fibromyalgia in 10% (95% CI 8% to 13%). Five studies of FND diagnoses among 361 patients with chronic pain were identified. Most interventions for FND did not ameliorate pain, even when other symptoms improved.

CONCLUSIONS: Pain symptoms and pain-related diagnoses are common in FND. Classification systems and treatments should routinely consider pain as a comorbidity in patients with FND.}, } @article {pmid38382771, year = {2024}, author = {MacCallum-Bridges, C and Hirschtick, JL and Patel, A and Orellana, RC and Elliott, MR and Fleischer, NL}, title = {The impact of COVID-19 vaccination prior to SARS-CoV-2 infection on prevalence of long COVID among a population-based probability sample of Michiganders, 2020-2022.}, journal = {Annals of epidemiology}, volume = {92}, number = {}, pages = {17-24}, doi = {10.1016/j.annepidem.2024.02.007}, pmid = {38382771}, issn = {1873-2585}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines/therapeutic use ; Prevalence ; Sampling Studies ; SARS-CoV-2 ; Vaccination ; }, abstract = {PURPOSE: To estimate the association between COVID-19 vaccination status at the time of COVID-19 onset and long COVID prevalence.

METHODS: We used data from the Michigan COVID-19 Recovery Surveillance Study, a population-based probability sample of adults with COVID-19 (n = 4695). We considered 30-day and 90-day long COVID (illness duration ≥30 or ≥90 days, respectively), using Poisson regression to estimate prevalence ratios (PRs) comparing vaccinated (completed an initial series ≥14 days before COVID-19 onset) to unvaccinated individuals (received 0 doses before COVID-19 onset), accounting for differences in age, sex, race and ethnicity, education, employment, health insurance, and rurality/urbanicity. The full unvaccinated comparison group was further divided into historic and concurrent comparison groups based on timing of COVID-19 onset relative to vaccine availability. We used inverse probability of treatment weights to account for sociodemographic differences between groups.

RESULTS: Compared to the full unvaccinated comparison group, the adjusted prevalence of 30-day and 90-day long COVID were lower among vaccinated individuals [PR30-day= 0.57(95%CI:0.49,0.66); PR90-day= 0.42(95%CI:0.34,0.53)]. Estimates were consistent across comparison groups (full, historic, and concurrent).

CONCLUSIONS: Long COVID prevalence was 40-60% lower among adults vaccinated (vs. unvaccinated) prior to their COVID-19 onset. COVID-19 vaccination may be an important tool to reduce the burden of long COVID.}, } @article {pmid38381899, year = {2024}, author = {Santos, KSDC and Brito, GMG and Melo, EV and Sousa, ACS and Martins-Filho, PR and Campos, MDSB}, title = {Cardiorespiratory optimal point in post-COVID-19 patients: a cross-sectional study.}, journal = {Revista do Instituto de Medicina Tropical de Sao Paulo}, volume = {66}, number = {}, pages = {e14}, pmid = {38381899}, issn = {1678-9946}, mesh = {Male ; Female ; Humans ; *COVID-19 ; Cross-Sectional Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Exercise Test ; }, abstract = {The varied clinical presentations of SARS-CoV-2 infection have raised concerns about long-term consequences, especially "long-COVID" or "post-COVID-19 syndrome." In this context, the cardiorespiratory optimal point (COP) within the Cardiopulmonary Exercise Test (CPET) emerges as a crucial metric for evaluating functional capacities and detecting cardiovascular and pulmonary anomalies post-COVID-19. This study aimed to assess COP values among post-COVID-19 patients and categorized them based on the initial severity of their disease. In this cross-sectional study conducted in the Northeast Brazil, 80 patients (26 females and 54 males) previously infected with SARS-CoV-2 underwent CPET. We clinically stratified patients into mild, moderate, or severe COVID-19 categories and assessed COP values and other cardiorespiratory metrics. We found differences in the predicted COP between patients with mild and severe COVID-19 (p=0.042). Additionally, patients with moderate and severe COVID-19 record had an average COP value exceeding 22. Other parameters, including respiratory exchange ratio, heart rate, and oxygen uptake efficiency slope, did not differ across the groups. Patients with a history of severe COVID-19 showed altered COP values, suggesting potential discrepancies in cardiovascular and respiratory system integration. The outcomes emphasize the importance of continuous monitoring and assessment of the cardiorespiratory domain for post-COVID-19 patients. Further research is needed to understand the relationship between elevated COP in post-severe COVID-19 and its long-term prognostic implications.}, } @article {pmid38381866, year = {2024}, author = {Ramos, AN}, title = {Long COVID challenges in Brazil: an unfinished agenda for the Brazilian Unified National Health System.}, journal = {Cadernos de saude publica}, volume = {40}, number = {2}, pages = {e00008724}, pmid = {38381866}, issn = {1678-4464}, mesh = {Humans ; Brazil/epidemiology ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Health Policy ; Delivery of Health Care ; National Health Programs ; }, } @article {pmid38381822, year = {2024}, author = {Krishna, BA and Lim, EY and Metaxaki, M and Jackson, S and Mactavous, L and , and Lyons, PA and Doffinger, R and Bradley, JR and Smith, KGC and Sinclair, J and Matheson, NJ and Lehner, PJ and Sithole, N and Wills, MR}, title = {Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.}, journal = {Science advances}, volume = {10}, number = {8}, pages = {eadi9379}, pmid = {38381822}, issn = {2375-2548}, support = {MR/V028448/1/MRC_/Medical Research Council/United Kingdom ; 200871/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MR/V011561/1/MRC_/Medical Research Council/United Kingdom ; MR/W018861/1/MRC_/Medical Research Council/United Kingdom ; MR/T032413/1/MRC_/Medical Research Council/United Kingdom ; MR/S00081X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Biomarkers ; CD8-Positive T-Lymphocytes ; *COVID-19 ; *Interferon-gamma ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8[+] T cell-mediated and dependent on antigen presentation by CD14[+] cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.}, } @article {pmid38381595, year = {2024}, author = {Tsampasian, V and Bäck, M and Bernardi, M and Cavarretta, E and Dębski, M and Gati, S and Hansen, D and Kränkel, N and Koskinas, K and Niebauer, J and Spadafora, L and Frias Vargas, M and Biondi-Zoccai, G and Vassiliou, VS}, title = {Cardiovascular disease as part of Long COVID: A systematic review.}, journal = {European journal of preventive cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjpc/zwae070}, pmid = {38381595}, issn = {2047-4881}, abstract = {BACKGROUND: Long COVID syndrome has had a major impact on million patients' lives worldwide. The cardiovascular system is an important aspect of this multifaceted disease that may manifest in many ways. We have hereby performed a narrative review in order to identify the extent of the cardiovascular manifestations of the Long COVID syndrome.

METHODS AND RESULTS: An in-depth systematic search of the literature has been conducted for this narrative review. The systematic search of PubMed and Cochrane databases yielded 3,993, of which 629 underwent full text screening. A total of 78 studies were included in the final qualitative synthesis and data evaluation. The pathophysiology of the cardiovascular sequelae of Long COVID syndrome and the cardiac manifestations and complications of Long COVID syndrome are critically evaluated. In addition, potential cardiovascular risk factors are assessed, and preventive methods and treatment options are examined in this review.

CONCLUSIONS: This systematic review poignantly summarises the evidence from the available literature regarding the cardiovascular manifestations of Long COVID syndrome and reviews potential mechanistic pathways, diagnostic approaches, preventive measures and treatment options.}, } @article {pmid38381452, year = {2024}, author = {Harris, E}, title = {Virtual Group Exercise Program Improved Long COVID Symptoms.}, journal = {JAMA}, volume = {331}, number = {10}, pages = {822}, doi = {10.1001/jama.2024.0734}, pmid = {38381452}, issn = {1538-3598}, mesh = {Humans ; COVID-19/complications ; *Exercise Therapy/methods ; *Post-Acute COVID-19 Syndrome/diagnosis/therapy ; *Telemedicine ; Treatment Outcome ; }, } @article {pmid38380901, year = {2024}, author = {Biserni, C and De Groot, BO and Fuermaier, ABM and de Waard, D and Enriquez-Geppert, S}, title = {Post-COVID fatigue: Reduced quality-of-life associated with clinically relevant fatigue in mild disease courses.}, journal = {Neuropsychological rehabilitation}, volume = {34}, number = {9}, pages = {1302-1326}, doi = {10.1080/09602011.2024.2314874}, pmid = {38380901}, issn = {1464-0694}, mesh = {Humans ; *COVID-19/complications ; *Quality of Life ; Male ; Female ; Middle Aged ; Adult ; *Fatigue/etiology ; *Severity of Illness Index ; Surveys and Questionnaires ; Aged ; Mental Fatigue/etiology ; Young Adult ; SARS-CoV-2 ; }, abstract = {Fatigue is a pervasive symptom experienced by many individuals after COVID-19. Despite its widespread occurrence, fatigue remains a poorly understood and complex phenomenon. Our aim is to evaluate the subjective experience of mental fatigue after COVID-19 and to assess its significance for daily life functioning. In this online questionnaire study (N = 220), the Fatigue Severity Scale (FSS), World Health Organization Quality-of-Life assessment (WHOQoL) and a subjective severity rating of the COVID-19 disease progression were used. For our statistical analyses we utilized independent samples t-tests, one-way ANOVA with post-hoc analyses, and a multiple regression. As expected our findings revealed the COVID group reported significantly higher levels of subjective fatigue compared to the control group. Moreover, there was a significant difference between experienced fatigue across the four severity groups. Participants who had a milder course of disease also experienced severe subjective fatigue. Subjective fatigue explained 40% variance in quality-of-life. In conclusion, severe subjective fatigue appears to be associated with increased self-reported COVID-19 symptom severity and lower quality-of-life but is already observable in milder cases. This underscores, firstly, the importance of considering also less severe cases and, secondly, the need to develop rehabilitation and psychological interventions for fatigue.}, } @article {pmid38380482, year = {2024}, author = {Warnaerts, N and Beeckmans, K and Morrens, M and De Picker, L}, title = {[Impairments in neurocognitive functions in patients with long COVID: A systematic review].}, journal = {Tijdschrift voor psychiatrie}, volume = {66}, number = {1}, pages = {12-18}, pmid = {38380482}, issn = {0303-7339}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Neuropsychological Tests ; Case-Control Studies ; *COVID-19/complications ; Executive Function ; }, abstract = {BACKGROUND: Studies have shown impairments in neurocognitive functions which persist more than 3&nbsp;months after COVID-19 (long COVID). It remains unclear what these impairments entail, how long they persist and what proportion of the patients exhibit them.

AIM: To define the specific neurocognitive profile and to determine the proportion of deficits in at least one cognitive domain in patients with long COVID.

METHOD: We conducted a systematic search in PubMed according to PRISMA 2020 guidelines with the following inclusion criteria: peer reviewed publications in which patients were assessed more than 3&nbsp;months following acute COVID-19 by means of a test battery for different domains of neurocognition.

RESULTS: We found a total of 1178 papers, of which 7 cohort studies and 1 case-control study were selected. The proportion of patients having deficits in at least one domain of neurocognition ranged from 23% to 100%. Most frequent impairments were found in attention and speed of information processing, anterograde memory, working memory and executive function. Quality of the included studies was moderate.

CONCLUSION: Impairments in neurocognitive functions are highly prevalent among patients with long COVID and include various cognitive domains. We encourage further research to continue studying the complex interaction of COVID-19, neurocognitive impairments and neuropsychiatric syndromes.}, } @article {pmid38380019, year = {2024}, author = {Schröder, D and Heinemann, S and Heesen, G and Hummers, E and Schmachtenberg, T and Dopfer-Jablonka, A and Vahldiek, K and Klawonn, F and Klawitter, S and Steffens, S and Mikuteit, M and Niewolik, J and Müller, F}, title = {Association of long COVID with health-related Quality of Life and Social Participation in Germany: Finding from an online-based cross-sectional survey.}, journal = {Heliyon}, volume = {10}, number = {4}, pages = {e26130}, pmid = {38380019}, issn = {2405-8440}, abstract = {PURPOSE: This study aims to examine the health-related Quality of Life (hrQoL) and social participation in participants with Long COVID compared to participants without symptoms after COVID-19 and participants with no prior SARS-CoV-2 infection.

METHODS: A cross-sectional online survey was conducted in Germany. The non-random sample consists of participants 18 years or older. Participants were divided in three groups: Lg COVID with a prior SARS-CoV-2 infection and new or persistent symptoms 28 days after infection, ExCOVID with a prior SARS-CoV-2 infection and without new or persistent symptoms after 28 days, and NoCOVID when participants had no prior SARS-CoV-2 infection. EQ-5D-3L was used as hrQoL measure and the Index for the Assessment of Health Impairments (IMET) to reflect social participation. Descriptive and inferential statistics were performed.

RESULTS: A total of 3188 participants were included in the analysis (1421 Lg COVID, 260 ExCOVID, 1507 NoCOVID). Lg COVID was associated with the lowest EQ-5D-3L index values (p < 0.001), Visual Analogue Scale (VAS) scores (p < 0.001), and IMET (p < 0.001) scores followed by NoCOVID and ExCOVID. After adjusting for sociodemographic and medical conditions in a multivariable model Long COVID was still associated with lower hrQoL compared to NoCOVID (p < 0.001). About 10% of Lg COVID participants showed no health impairments in all EQ-5D dimensions while 51.1% of NoCOVID and 60% of ExCOVID participants showed no health impairments.

CONCLUSION: This study highlights the impairments of persons with Long COVID on hrQoL and social participation compared to individuals without Long COVID in Germany.

TRIAL REGISTRATION: German Clinical Trial Registry, DRKS00026007.}, } @article {pmid38378550, year = {2024}, author = {Valencia, I and Lumpuy-Castillo, J and Magalhaes, G and Sánchez-Ferrer, CF and Lorenzo, Ó and Peiró, C}, title = {Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.}, journal = {Cardiovascular diabetology}, volume = {23}, number = {1}, pages = {75}, pmid = {38378550}, issn = {1475-2840}, support = {CD22/00101//Instituto de Salud Carlos III/ ; FPI-UAM//Universidad Autónoma de Madrid/ ; Maria Zambrano postdoctoral grant//European Union-Next Generation EU/ ; SAF2017-84776-R//Ministerio de Economía y Competitividad/ ; P120/00923//Instituto de Salud Carlos III and Fondo de Investigaciones Sanitarias/ ; SPACE2-CV-COVID-CM//REACT-EU-Comunidad de Madrid and the European Regional Development Fund/ ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; *Thrombophilia/diagnosis/drug therapy ; *Thrombosis ; *Diabetes Mellitus/diagnosis/drug therapy/epidemiology ; Endothelium ; }, abstract = {Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced.}, } @article {pmid38377796, year = {2024}, author = {Yang, C and Shannon, CP and Tebbutt, SJ}, title = {Unravelling long COVID: insights from proteomics and considerations for comprehensive understanding.}, journal = {EBioMedicine}, volume = {101}, number = {}, pages = {105023}, pmid = {38377796}, issn = {2352-3964}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Proteomics ; }, } @article {pmid38377114, year = {2024}, author = {Mkoma, GF and Agyemang, C and Benfield, T and Rostila, M and Cederström, A and Petersen, JH and Norredam, M}, title = {Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: A nationwide register-linked cohort study in Denmark.}, journal = {PLoS medicine}, volume = {21}, number = {2}, pages = {e1004280}, pmid = {38377114}, issn = {1549-1676}, mesh = {*COVID-19/epidemiology ; Adult ; Asian People ; Ethnic and Racial Minorities ; North African People ; Denmark/epidemiology ; Humans ; Eastern European People ; Post-Acute COVID-19 Syndrome ; *Scandinavians and Nordic People ; East African People ; Cohort Studies ; Minority Groups ; Adolescent ; SARS-CoV-2 ; Middle Eastern People ; Ethnicity ; }, abstract = {BACKGROUND: Ethnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities.

METHODS AND FINDINGS: We used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,287,175) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], p = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], p < 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], p < 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], p = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], p < 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], p < 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], p = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital.

CONCLUSIONS: Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations.}, } @article {pmid38375735, year = {2024}, author = {Ribeiro, J and Caldeira, D and Dores, H}, title = {Long-term manifestations of COVID-19 in athletes: a narrative review.}, journal = {The Physician and sportsmedicine}, volume = {52}, number = {5}, pages = {452-459}, doi = {10.1080/00913847.2024.2321629}, pmid = {38375735}, issn = {2326-3660}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *Athletes ; *Return to Sport ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Athletic Performance/physiology ; Fatigue/physiopathology/etiology ; }, abstract = {BACKGROUND: Long COVID is a condition where symptoms or complications persist beyond 3 months after COVID-19 infection. Although most athletes experience mild symptoms, those involved in sports with higher cardiovascular demands can develop long COVID, which can negatively impact sports performance. This narrative review aimed to analyze the long COVID in athletes, especially cardiovascular effects; to alert medical and sporting community for the clinical aftermaths of COVID-19, focusing on physical activity; and to discuss the potential return-to-play strategies for these athletes.

METHODS: An electronic search in PubMed database for articles published between January/2020 and February/2023 was performed including athletic populations with COVID-19, emphasizing long-term complications, especially the cardiovascular effects.

RESULTS AND CONCLUSIONS: While severe cardiac complications are rare, athletes with long COVID often experience symptoms such as fatigue, dyspnea, palpitations, and exercise intolerance. To manage athletes with long COVID, individualized and structured return-to-play programs with the involvement of multidisciplinary teams are crucial. This underscores the importance of recognizing long COVID in athletes, raising awareness of its potential impacts, and implementing strategies to ensure a safe return to play.}, } @article {pmid38374794, year = {2024}, author = {Lindbergh, CA and Altizer, R and Grady, JJ and Diniz, BS and Kamath, J and Steffens, DC and Morimoto, SS}, title = {Computerized cognitive remediation of Long COVID in older adults.}, journal = {International psychogeriatrics}, volume = {36}, number = {12}, pages = {1267-1269}, doi = {10.1017/S1041610224000139}, pmid = {38374794}, issn = {1741-203X}, } @article {pmid38374172, year = {2024}, author = {El-Medany, A and Adams, ZH and Blythe, HC and Hope, KA and Kendrick, AH and Abdala Sheikh, AP and Paton, JFR and Nightingale, AK and Hart, EC}, title = {Carotid body dysregulation contributes to Long COVID symptoms.}, journal = {Communications medicine}, volume = {4}, number = {1}, pages = {20}, pmid = {38374172}, issn = {2730-664X}, abstract = {BACKGROUND: The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID.

METHODS: Non-hositalised participants with long-COVID (n = 14) and controls (n = 14) completed hypoxic ventilatory response (HVR; the measure of carotid chemoreflex sensitivity) and cardiopulmonary exercise tests. Parametric and normally distributed data were compared using Student's unpaired t-tests or ANOVA. Nonparametric equivalents were used where relevant. Peason's correlation coefficient was used to examine relationships between variables.

RESULTS: During cardiopulmonary exercise testing the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group (37.8 ± 4.4) compared to controls (27.7 ± 4.8, P = 0.0003), indicating excessive hyperventilation. The HVR was increased in long COVID participants (-0.44 ± 0.23 l/min/ SpO2%, R[2] = 0.77 ± 0.20) compared to controls (-0.17 ± 0.13 l/min/SpO2%, R[2] = 0.54 ± 0.38, P = 0.0007). The HVR correlated with the VE/VCO2 slope (r = -0.53, P = 0.0036), suggesting that excessive hyperventilation may be related to carotid body hypersensitivity.

CONCLUSIONS: The carotid chemoreflex is sensitised in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.}, } @article {pmid38372528, year = {2024}, author = {Maybin, JA and Watters, M and Rowley, B and Walker, CA and Sharp, GC and Alvergne, A}, title = {COVID-19 and abnormal uterine bleeding: potential associations and mechanisms.}, journal = {Clinical science (London, England : 1979)}, volume = {138}, number = {4}, pages = {153-171}, pmid = {38372528}, issn = {1470-8736}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Female ; Humans ; *Endometrium ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Vaccines ; *COVID-19/complications ; SARS-CoV-2 ; Menstruation/physiology ; Uterine Hemorrhage/etiology ; Menstruation Disturbances/complications ; }, abstract = {The impact of COVID-19 on menstruation has received a high level of public and media interest. Despite this, uncertainty exists about the advice that women and people who menstruate should receive in relation to the expected impact of SARS-CoV-2 infection, long COVID or COVID-19 vaccination on menstruation. Furthermore, the mechanisms leading to these reported menstrual changes are poorly understood. This review evaluates the published literature on COVID-19 and its impact on menstrual bleeding, discussing the strengths and limitations of these studies. We present evidence consistent with SARS-CoV-2 infection and long COVID having an association with changes in menstrual bleeding parameters and that the impact of COVID vaccination on menstruation appears less significant. An overview of menstrual physiology and known causes of abnormal uterine bleeding (AUB) is provided before discussing potential mechanisms which may underpin the menstrual disturbance reported with COVID-19, highlighting areas for future scientific study. Finally, consideration is given to the effect that menstruation may have on COVID-19, including the impact of the ovarian sex hormones on acute COVID-19 severity and susceptibility and reported variation in long COVID symptoms across the menstrual cycle. Understanding the current evidence and addressing gaps in our knowledge in this area are essential to inform public health policy, direct the treatment of menstrual disturbance and facilitate development of new therapies, which may reduce the severity of COVID-19 and improve quality of life for those experiencing long COVID.}, } @article {pmid38371381, year = {2024}, author = {Sakib, MN and Saragadam, A and Santagata, MC and Jolicoeur-Becotte, M and Kozyr, L and Burhan, AM and Hall, PA}, title = {rTMS for post-covid-19 condition: A sham-controlled case series involving iTBS-300 and iTBS-600.}, journal = {Brain, behavior, & immunity - health}, volume = {36}, number = {}, pages = {100736}, pmid = {38371381}, issn = {2666-3546}, abstract = {Post-Covid-19 Condition (PCC) is a syndrome comprised of symptoms persisting 3 months or more beyond SARS-CoV-2 primary infection. It is typically characterized by fatigue, cognitive problems and psychiatric symptoms, as well as cardiac symptoms that contribute to exercise intolerance in many. Despite the high prevalence of PCC among those with a prior SARS-CoV-2 infection, there is currently no widely accepted rehabilitation strategy, and many conventional modalities are movement-based. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) may have some potential to alleviate the cognitive and affective symptoms of PCC without reliance on exercise. The purpose of the present study was to explore the feasibility and tolerability of using rTMS to treat symptoms of "brain fog" and affective disturbance among those living with PCC, using a case series design. We enrolled four individuals with PCC following a confirmed SARS-CoV-2 infection, at least 3 months after the resolution of the primary infection. Participants were randomized to 4 sessions of active and 2 sessions of sham intermittent theta-burst stimulation (iTBS); two intensities of iTBS were evaluated: iTBS-300 and iTBS-600. No adverse events occurred in active or sham stimulation; 2 participants reported tingling sensation on the scalp but no other tolerability issues. Trends in symptoms suggested improvements in cognitive interference, quality of life, and anxiety in the majority of participants. In summary, in this case series iTBS was well tolerated among 4 individuals with PCC; active stimulation was associated with positive trends in some primary symptom clusters as compared with sham stimulation. Future studies should examine the effects of iTBS on PCC symptoms in the context of experimental studies and randomized controlled trials.}, } @article {pmid38370700, year = {2024}, author = {Khan, R and Ji, W and Guzman-Rivera, J and Madhvi, A and Andrews, T and Richlin, B and Suarez, C and Gaur, S and Cuddy, W and Singh, AR and Bukulmez, H and Kaelber, D and Kimura, Y and Ganapathi, U and Michailidis, IE and Ukey, R and Moroso-Fela, S and Kuster, JK and Casseus, M and Roy, J and Kleinman, LC and Horton, DB and Lakhani, SA and Gennaro, ML}, title = {A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38370700}, support = {R01 AI158911/AI/NIAID NIH HHS/United States ; R33 HD105619/HD/NICHD NIH HHS/United States ; R61 HD105619/HD/NICHD NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; }, abstract = {Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rare LYST variant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.}, } @article {pmid38370438, year = {2024}, author = {Reid, KJ and Ingram, LT and Jimenez, M and Orban, ZS and Abbott, SM and Grimaldi, D and Knutson, KL and Zee, PC and Koralnik, IJ and Maas, MB}, title = {Impact of sleep disruption on cognitive function in patients with postacute sequelae of SARS-CoV-2 infection: initial findings from a Neuro-COVID-19 clinic.}, journal = {Sleep advances : a journal of the Sleep Research Society}, volume = {5}, number = {1}, pages = {zpae002}, pmid = {38370438}, issn = {2632-5012}, support = {P01 AG011412/AG/NIA NIH HHS/United States ; R01 HL140580/HL/NHLBI NIH HHS/United States ; }, abstract = {INTRODUCTION: Fatigue, brain fog, and sleep disturbance are among the most common symptoms of postacute sequelae of SARS-CoV-2 infection (PASC). We sought to determine the impact of sleep disruption on cognition and quality of life in patients with neurologic manifestations of PASC (Neuro-PASC).

METHODS: Thirty-nine patients were recruited from Neuro-COVID-19 clinic. Mean age was 48.1 years, 71.8% were female, and 82% were never hospitalized for COVID-19. Patients were evaluated via clinical assessment, quality-of-life measures in domains of cognitive function, fatigue, sleep disturbance, anxiety, and depression, NIH Toolbox cognitive tests, and 7 days of wrist actigraphy.

RESULTS: The median number of neurologic symptoms attributed to PASC was 6, with brain fog being the most common in 89.7%. Regarding non-neurologic symptoms, 94.9% complained of fatigue and 74.4% of insomnia. Patients reported significant impairment in all quality-of-life domains and performed worse in a task of attention compared to a normative US population. Actigraphy showed Neuro-PASC patients had lower sleep efficiency, longer sleep latency (both p < 0.001), and later sleep midpoint (p = 0.039) compared to 71 age-matched healthy controls with no PASC history. Self-reported cognitive symptoms correlated with the severity of fatigue (p < 0.001), anxiety (p = 0.05), and depression (p < 0.01). Objective evidence of sleep disruption measured by wakefulness after sleep onset, sleep efficiency, and latency were associated with decreased performance in attention and processing speed.

CONCLUSION: Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep disruption on the cognitive function and quality of life of patients with PASC.}, } @article {pmid38370437, year = {2024}, author = {Kujawski, S and Zalewski, P and Hodges, L and Nijs, J and Newton, JL}, title = {Editorial: Fatigue: physiology and pathology.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1368897}, pmid = {38370437}, issn = {1662-4548}, } @article {pmid38369723, year = {2024}, author = {Punj, M and Schwartz, M and Morris, A and Cheung, J and Munipalli, B}, title = {A Survey of Sleep Quality From a Post-COVID Clinic.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241233205}, pmid = {38369723}, issn = {2150-1327}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; Sleep Quality ; Patient Reported Outcome Measures ; *COVID-19/complications/epidemiology ; Surveys and Questionnaires ; *Sleep Wake Disorders/epidemiology/etiology ; Sleep ; }, abstract = {OBJECTIVES: To assess the prevalence of sleep disturbance among patients evaluated at a clinic for patients afflicted with Post-acute sequelae of COVID-19 (PASC).

METHODS: Sleep disturbance was assessed with the Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) framework among adult patients of the PASC clinic.

RESULTS: Among 312 patients, the mean age was 46.2 years, and 70.2% were women. About 41.0% of patients had no sleep disturbance; sleep disturbance was mild to moderate in 51.3% and severe in 7.7%. PROMIS-SD score was negatively correlated with the time from the initial positive COVID-19 test to the initial consultation in the PASC clinic (Pearson r = -.094; r[2] = .0088).

CONCLUSIONS: The PROMIS-Sleep Disturbance framework can serve as a tool to assess the burden of sleep disturbances in PASC patients.}, } @article {pmid38367953, year = {2024}, author = {Berentschot, JC and Martine Bek, L and Heijenbrok-Kal, MH and van den Berg-Emons, RJG and Ribbers, GM and Aerts, JGJV and Hellemons, ME and , }, title = {Acute COVID-19 treatment is not associated with health problems 2 years after hospitalization.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {142}, number = {}, pages = {106966}, doi = {10.1016/j.ijid.2024.02.009}, pmid = {38367953}, issn = {1878-3511}, mesh = {Female ; Humans ; Male ; Anti-Inflammatory Agents ; Antiviral Agents/therapeutic use ; Cohort Studies ; *COVID-19 ; COVID-19 Drug Treatment ; Hospitalization ; Prospective Studies ; Quality of Life ; Retrospective Studies ; SARS-CoV-2 ; Middle Aged ; Aged ; }, abstract = {OBJECTIVES: Various mechanisms, such as immune dysregulation, viral reservoir, and auto-immunity, are hypothesized to underlie the pathogenesis of long-term health problems after hospitalization for COVID-19. We aimed to assess the effect of in-hospital COVID-19 treatments on prominent long-term health problems.

METHODS: In this prospective multicenter cohort study, we enrolled patients (age ≥18 years) who had been hospitalized for COVID-19 in the Netherlands between July 2020 and October 2021. We retrospectively collected data on in-hospital COVID-19 treatments, including steroid, anti-inflammatory, and antiviral treatments. Patients completed questionnaires on self-reported recovery, dyspnea, fatigue, cognitive failures, and health-related quality of life and performed the 6-minute walk test at the 2-year follow-up visit.

RESULTS: Five hundred two patients with COVID-19 were included, all were discharged from the hospital between March 2020 and June 2021. The median age at admission was 60.0 (IQR 53.0-68.0) years and 350 (69.7%) patients were male. At hospital admission, 5/405 (1.2%) of the patients had been vaccinated against SARS-CoV-2. Among all 502 patients, the majority (248 [49.4%]) received steroids only, 57 (11.4%) anti-inflammatory treatment, 78 (15.5%) antiviral treatment, and 119 (23.7%) none during hospitalization. Long-term health problems were common in all groups. We found that in-hospital treatments were not significantly associated with health problems at 2 years after hospital discharge, nor after adjusting for confounders.

CONCLUSION: Many patients with COVID-19 suffer from long-term health problems 2 years after hospital discharge. Acute treatment for COVID-19 is not associated with long-term health problems.}, } @article {pmid38367845, year = {2024}, author = {Merle-Nguyen, L and Ando-Grard, O and Bourgon, C and St Albin, A and Jacquelin, J and Klonjkowski, B and Le Poder, S and Meunier, N}, title = {Early corticosteroid treatment enhances recovery from SARS-CoV-2 induced loss of smell in hamster.}, journal = {Brain, behavior, and immunity}, volume = {118}, number = {}, pages = {78-89}, doi = {10.1016/j.bbi.2024.02.020}, pmid = {38367845}, issn = {1090-2139}, mesh = {Humans ; Animals ; Cricetinae ; SARS-CoV-2 ; Smell/physiology ; *COVID-19 ; Anosmia/drug therapy ; Post-Acute COVID-19 Syndrome ; *Olfaction Disorders ; Adrenal Cortex Hormones ; Inflammation ; }, abstract = {Among the numerous long COVID symptoms, olfactory dysfunction persists in ∼10 % of patients suffering from SARS-CoV-2 induced anosmia. Among the few potential therapies, corticoid treatment has been used for its anti-inflammatory effect with mixed success in patients. In this study, we explored its impact using hamster as an animal model. SARS-CoV-2 infected hamsters lose their smell abilities and this loss is correlated with damage of the olfactory epithelium and persistent presence of innate immunity cells. We started a dexamethasone treatment 2 days post infection, when olfaction was already impacted, until 11 days post infection when it started to recover. We observed an improvement of olfactory capacities in the animals treated with corticoid compared to those treated with vehicle. This recovery was not related to differences in the remaining damage to the olfactory epithelium, which was similar in both groups. This improvement was however correlated with a reduced inflammation in the olfactory epithelium with a local increase of the mature olfactory neuron population. Surprisingly, at 11 days post infection, we observed an increased and disorganized presence of immature olfactory neurons, especially in persistent inflammatory zones of the epithelium. This unusual population of immature olfactory neurons coincided with a strong increase of olfactory epithelium proliferation in both groups. Our results indicate that persistent inflammation of the olfactory epithelium following SARS-CoV-2 infection may alter the extent and speed of regeneration of the olfactory neuron population, and that corticoid treatment is effective to limit inflammation and improve olfaction recovery following SARS-CoV-2 infection.}, } @article {pmid38367371, year = {2024}, author = {Sirotiak, Z and Thomas, EBK and Wade, NG and Brellenthin, AG}, title = {Associations between forgiveness and physical and mental health in the context of long COVID.}, journal = {Journal of psychosomatic research}, volume = {178}, number = {}, pages = {111612}, doi = {10.1016/j.jpsychores.2024.111612}, pmid = {38367371}, issn = {1879-1360}, mesh = {Adult ; Humans ; Female ; United States ; Mental Health ; *Forgiveness ; Post-Acute COVID-19 Syndrome ; Health Status ; Cross-Sectional Studies ; *COVID-19 ; }, abstract = {OBJECTIVE: Forgiveness has been positively associated with health in those with functional disorders. This cross-sectional study examined the relationships among dimensions of forgiveness and physical and mental health in individuals with and without long COVID.

METHODS: Adults (N = 4316) in the United States took part in an online survey study detailing long COVID presence, physical and mental health, and trait forgiveness. T-tests were performed to assess differences in types of trait forgiveness between individuals with and without long COVID. Linear regression models assessed the contribution of demographic covariates and forgiveness subscales to the physical and mental health of individuals with and without long COVID.

RESULTS: Of 4316 participants, 379 (8.8%) reported current long COVID. Participants were an average age of 43.7, and most identified as female (51.9%), white (87.8%), and non-Hispanic/Latino (86.6%). Individuals with long COVID reported significantly less forgiveness of self (p < 0.001, d = 0.33), forgiveness of others (p = 0.004, d = 0.16), and forgiveness of situations (p < 0.001, d = 0.34) than those without long COVID. Among the long COVID sample, forgiveness of self and situations were positively associated with mental health (p < 0.05), but not physical health (p > 0.05). Forgiveness of others was negatively associated with both physical and mental health (p < 0.05).

CONCLUSION: Forgiveness may be an important consideration in understanding health among individuals with long COVID, emphasizing the importance of developing a multifaceted understanding of the condition.}, } @article {pmid38366966, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Macasaet, R and Velasco, JV and Ver, AT and Culasino Carandang, THD and Guerrero, JJ and Franco-Moreno, A and Chung, W and Notarte, KI}, title = {Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature.}, journal = {Clinical chemistry and laboratory medicine}, volume = {62}, number = {6}, pages = {1044-1052}, pmid = {38366966}, issn = {1437-4331}, mesh = {Humans ; *COVID-19/virology/diagnosis ; *RNA, Viral/analysis ; *SARS-CoV-2/isolation & purification/genetics ; Survivors ; Feces/virology/chemistry ; Female ; }, abstract = {INTRODUCTION: Viral persistence is one of the main hypotheses explaining the presence of post-COVID symptoms. This systematic review investigated the presence of SARS-CoV-2 RNA in plasma, stool, urine, and nasal/oral swab samples in individuals with post-COVID symptomatology.

CONTENT: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to November 25th, 2023. Articles investigating the persistence of SARS-CoV-2 RNA in plasma, stool, urine or nasal/oral swab samples in patients with post-COVID symptoms were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool.

SUMMARY: From 322 studies identified, six studies met all inclusion criteria. The sample included 678 COVID-19 survivors (52 % female, aged from 29 to 66 years). The methodological quality was moderate in 88 % of the studies (n=5/6). Three papers investigated the presence of SARS-CoV-2 RNA in plasma, three studies in nasal/oral swabs, two studies in stool samples, one in urine and one in saliva. The follow-up was shorter than two months (<60 days after) in 66 % of the studies (n=4/6). The prevalence of SARS-CoV-2 RNA ranged from 5 to 59 % in patients with post-COVID symptoms the first two months after infection, depending on the sample tested, however, SARS-CoV-2 RNA was also identified in COVID-19 survivors without post-COVID symptoms (one study).

OUTLOOK: Available evidence can suggest the presence of persistent SARS-CoV-2 RNA in post-COVID patients in the short term, although the biases within the studies do not permit us to make firm assumptions. The association between post-COVID symptoms and SARS-CoV-2 RNA in the samples tested is also conflicting. The lack of comparative group without post-COVID symptoms limits the generalizability of viral persistence in post-COVID-19 condition.}, } @article {pmid38366677, year = {2024}, author = {Bolstad, CJ and Holzinger, B and Scarpelli, S and De Gennaro, L and Yordanova, J and Koumanova, S and Mota-Rolim, S and Benedict, C and Bjorvatn, B and Chan, NY and Chung, F and Dauvilliers, Y and Espie, CA and Inoue, Y and Korman, M and Koscec Bjelajac, A and Landtblom, AM and Matsui, K and Merikanto, I and Morin, CM and Partinen, M and Penzel, T and Plazzi, G and Reis, C and Ross, B and Wing, YK and Nadorff, MR}, title = {Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic.}, journal = {Journal of sleep research}, volume = {33}, number = {5}, pages = {e14165}, doi = {10.1111/jsr.14165}, pmid = {38366677}, issn = {1365-2869}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Suicidal Ideation ; Female ; Male ; Middle Aged ; Adult ; Risk Factors ; *Dreams/psychology ; Surveys and Questionnaires ; Aged ; Young Adult ; }, abstract = {The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.}, } @article {pmid38361434, year = {2024}, author = {Von Nordheim, D and Johnson, M and Caburnay, C and Alleman, S and Kreuter, M and McQueen, A}, title = {Describing the Lived Experience and Resource Needs of Individuals With Long COVID.}, journal = {Health promotion practice}, volume = {25}, number = {6}, pages = {963-970}, doi = {10.1177/15248399241228823}, pmid = {38361434}, issn = {1524-8399}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Female ; Male ; Middle Aged ; Adult ; SARS-CoV-2 ; Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Health Services Needs and Demand ; }, abstract = {Individuals with long COVID report diverse symptoms lasting weeks or months after initial infection, causing significant psychosocial distress. Navigating health care interactions are often difficult for these individuals due to the diffuse nature of their symptoms, a lack of effective treatment options, and skepticism from some providers. To better understand these challenges, this study sought to further describe the lived experience of individuals with long COVID. A survey was conducted with individuals evaluated for long COVID at a specialty clinic (n = 200), which included questions about prior conditions, symptoms, use of medical and support services, and information and resource needs. Participants reported a mean of 10.75 persistent symptoms, the most common being fatigue and difficulty concentrating, with broad effects on daily functioning. Participants saw a mean of 5.92 providers for treatment of their symptoms, and 88.5% identified health care providers as a trusted source of information. Interest in research findings (60.5%) and opportunities for participation (47.5%) were moderate and varied by COVID vaccination status. Unvaccinated individuals (n = 27) also reported less trust in government sources of information, less college education, lower household income, and greater likelihood of having public insurance. Our findings suggest that individuals with long COVID experience many ongoing and complex symptoms with diverse effects on daily living; that health care providers are an important source for public health messaging about long COVID; and that unvaccinated individuals are likely to have differing needs and receptiveness to information than vaccinated individuals with long COVID.}, } @article {pmid38360929, year = {2024}, author = {Hadanny, A and Zilberman-Itskovich, S and Catalogna, M and Elman-Shina, K and Lang, E and Finci, S and Polak, N and Shorer, R and Parag, Y and Efrati, S}, title = {Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {3604}, pmid = {38360929}, issn = {2045-2322}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Follow-Up Studies ; *COVID-19/therapy ; Pain ; }, abstract = {In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47-0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.}, } @article {pmid38359962, year = {2024}, author = {Seylanova, N and Chernyavskaya, A and Degtyareva, N and Mursalova, A and Ajam, A and Xiao, L and Aktulaeva, K and Roshchin, P and Bobkova, P and Aiyegbusi, OL and Anbu, AT and Apfelbacher, C and Asadi-Pooya, AA and Ashkenazi-Hoffnung, L and Brackel, C and Buonsenso, D and de Groote, W and Diaz, JV and Dona, D and Dunn Galvin, A and Genuneit, J and Goss, H and Hughes, SE and Jones, CJ and Kuppalli, K and Malone, LA and McFarland, S and Needham, DM and Nekliudov, N and Nicholson, TR and Oliveira, CR and Schiess, N and Segal, TY and Sigfrid, L and Thorne, C and Vijverberg, S and Warner, JO and Were, WM and Williamson, PR and Munblit, D and , }, title = {Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".}, journal = {The European respiratory journal}, volume = {63}, number = {3}, pages = {}, pmid = {38359962}, issn = {1399-3003}, support = {001/WHO_/World Health Organization/International ; K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Humans ; *COVID-19 ; Delphi Technique ; Outcome Assessment, Health Care ; *Post-Acute COVID-19 Syndrome ; Research Design ; Treatment Outcome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.}, } @article {pmid38359836, year = {2024}, author = {Baillie, K and Davies, HE and Keat, SBK and Ladell, K and Miners, KL and Jones, SA and Mellou, E and Toonen, EJM and Price, DA and Morgan, BP and Zelek, WM}, title = {Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID.}, journal = {Med (New York, N.Y.)}, volume = {5}, number = {3}, pages = {239-253.e5}, doi = {10.1016/j.medj.2024.01.011}, pmid = {38359836}, issn = {2666-6340}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Complement System Proteins/metabolism ; Complement C3b ; }, abstract = {BACKGROUND: Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with SARS-CoV-2. The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID.

METHODS: We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/sex/infection/vaccine-matched patients with long COVID.

FINDINGS: Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785.

CONCLUSIONS: These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID.

FUNDING: This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute.}, } @article {pmid38359818, year = {2025}, author = {García-Hidalgo, MC and Benítez, ID and Perez-Pons, M and Molinero, M and Belmonte, T and Rodríguez-Muñoz, C and Aguilà, M and Santisteve, S and Torres, G and Moncusí-Moix, A and Gort-Paniello, C and Peláez, R and Larráyoz, IM and Caballero, J and Barberà, C and Nova-Lamperti, E and Torres, A and González, J and Barbé, F and de Gonzalo-Calvo, D}, title = {MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.}, journal = {British journal of pharmacology}, volume = {182}, number = {2}, pages = {380-395}, doi = {10.1111/bph.16330}, pmid = {38359818}, issn = {1476-5381}, support = {//Universitat de Lleida/ ; //Fundación Francisco Soria Melguizo/ ; COV20/00110//Instituto de Salud Carlos III/ ; CP20/00041//Instituto de Salud Carlos III/ ; CPII20/00029//Instituto de Salud Carlos III/ ; FI21/00187//Instituto de Salud Carlos III/ ; //Societat Catalana de Pneumologia/ ; SLT028/23/000191//Departament de Salut, Generalitat de Catalunya/ ; //Programa de donaciones "Estar preparados" UNESPA/ ; 1222/2022//Sociedad Española de Neumología y Cirugía Torácica/ ; 1437/2023//Sociedad Española de Neumología y Cirugía Torácica/ ; }, mesh = {Humans ; *MicroRNAs/genetics ; Longitudinal Studies ; Pilot Projects ; *COVID-19/genetics/complications ; Male ; Middle Aged ; Female ; Aged ; *Survivors ; Drug Discovery ; COVID-19 Drug Treatment ; Lung ; SARS-CoV-2/genetics ; Adult ; }, abstract = {BACKGROUND AND PURPOSE: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications.

EXPERIMENTAL APPROACH: We conducted a longitudinal investigation including 119 critical COVID-19 survivors. A comprehensive pulmonary evaluation was performed in the short-term (median = 94.0 days after hospital discharge) and long-term (median = 358 days after hospital discharge). Plasma miRNAs were quantified at the short-term evaluation using the gold-standard technique, RT-qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation.

KEY RESULTS: In the short-term, 84% of the survivors exhibited impaired lung diffusion (DLCO < 80% of predicted). One year post-discharge, 54.4% of this patient subgroup still presented abnormal DLCO. Four feature selection methods identified two specific miRNAs, miR-9-5p and miR-486-5p, linked to persistent lung dysfunction. The downstream experimentally validated targetome included 1473 genes, with heterogeneous enriched pathways associated with inflammation, angiogenesis and cell senescence. Validation studies using RNA-sequencing and proteomic datasets emphasized the pivotal roles of cell migration and tissue repair in persistent lung dysfunction. The repositioning potential of the miRNA targets was limited.

CONCLUSION AND IMPLICATIONS: Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID-19 survivors, offering a promising approach for the development of targeted disease-modifying agents.

LINKED ARTICLES: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.}, } @article {pmid38359012, year = {2024}, author = {Ford, ND and Agedew, A and Dalton, AF and Singleton, J and Perrine, CG and Saydah, S}, title = {Notes from the Field: Long COVID Prevalence Among Adults - United States, 2022.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {73}, number = {6}, pages = {135-136}, pmid = {38359012}, issn = {1545-861X}, mesh = {Adult ; Humans ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; }, } @article {pmid38357361, year = {2024}, author = {Barnhill, J and Chilcoat, A and Kavalakatt, B and Mata, R and Tiedt, M and Roth, I}, title = {Different but the Same: Common Themes in Illness Experience Among People With Diverse Long COVID Symptoms and the Potential Benefits of Virtual Group Medical Visits.}, journal = {Journal of patient experience}, volume = {11}, number = {}, pages = {23743735241230144}, pmid = {38357361}, issn = {2374-3735}, support = {K01 AT011578/AT/NCCIH NIH HHS/United States ; T35 AG038047/AG/NIA NIH HHS/United States ; }, abstract = {Long coronavirus disease 2019 (COVID-19) is poorly understood, widespread and debilitating. Integrative medical group visits (IMGVs) provide group medical care virtually or in person and are reimbursed by insurance payors. IMGV introduces integrative modalities such as mindfulness, nutrition, and acupressure in a person-centered, supportive, and educational environment. To evaluate a telehealth IMGV program called Nourish to Flourish (N2F) for patients with long COVID, three researchers conducted a qualitative analysis of pre- and post-group individual interviews. Twenty-five patients provided interviews, of which fifteen included pre- and post-group individual interviews. Main themes were unpredictable symptom patterns, a common range of emotions associated with long COVID experience, reconceptualizing self-identity, multiple barriers to care in conventional settings, and connections formed in N2F. Although symptoms varied, N2F participants found commonalities in their experiences of living with long COVID. They empathized with one another regarding changing symptoms, inconsistent social support, shifting identities, and barriers to effective medical care.}, } @article {pmid38355648, year = {2024}, author = {Calcaterra, V and Tagi, VM and D'Auria, E and Lai, A and Zanelli, S and Montanari, C and Biganzoli, EM and Marano, G and Borghi, E and Massa, V and Riva, A and Zuccotti, G}, title = {Long-term effects of SARS-CoV-2 infection in hospitalized children: findings from an Italian single-center study.}, journal = {Italian journal of pediatrics}, volume = {50}, number = {1}, pages = {27}, pmid = {38355648}, issn = {1824-7288}, support = {COVICIS project number 101046041//Horizon 2020/ ; }, mesh = {Adolescent ; Infant ; Humans ; Child ; *Child, Hospitalized ; SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Italy/epidemiology ; }, abstract = {BACKGROUND: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms.

METHODS: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge.

RESULTS: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta).

CONCLUSIONS: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age.}, } @article {pmid38355026, year = {2024}, author = {Murata, F and Maeda, M and Murayama, K and Nakao, T and Fukuda, H}, title = {Associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough SARS-CoV-2 infection: The VENUS Study.}, journal = {Brain, behavior, and immunity}, volume = {117}, number = {}, pages = {521-528}, doi = {10.1016/j.bbi.2024.02.018}, pmid = {38355026}, issn = {1090-2139}, mesh = {Humans ; SARS-CoV-2 ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Retrospective Studies ; *Mental Disorders/epidemiology ; Vaccination ; }, abstract = {BACKGROUND: The associations between COVID-19 vaccination and post-COVID psychiatric disorders are unclear. Furthermore, it is uncertain if these associations differ depending on the dominant SARS-CoV-2 variant at the time of infection. This retrospective cohort study aimed to clarify the associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough infection according to the different variant periods in Japan.

METHODS: Medical claims data, COVID-19 case-related information, and vaccination records were collected from three Japanese municipalities. The study population comprised public insurance enrollees aged ≥65 years who developed COVID-19 between June 2021 and December 2022. The study exposure was each participant's vaccination status 14 days before infection, and the outcomes were the occurrence of psychiatric disorders within three months of infection. Multivariable logistic regression analyses were performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of vaccination for the occurrence of psychiatric disorders. Analyses were conducted for the Delta period (June to December 2021), Omicron BA.1/BA.2 period (January to June 2022), and Omicron BA.5 period (July to December 2022).

RESULTS: We analyzed 270 participants (vaccinated: 149) in the Delta period, 2,963 participants (vaccinated: 2,699) in the Omicron BA.1/BA.2 period, and 7,723 participants (vaccinated: 7,159) in the Omicron BA.5 period. During the Delta period, vaccinated participants had significantly lower odds for psychotic disorders (OR: 0.23, 95 % CI: 0.06-0.88, P = 0.032) than unvaccinated participants. During the Omicron BA.5 period, vaccinated participants had significantly lower odds for organic mental disorders (OR: 0.54, 95 % CI: 0.30-0.95, P = 0.033), psychotic disorders (OR: 0.31, 95 % CI: 0.19-0.53, P < 0.001), mood disorders (OR: 0.53, 95 % CI: 0.29-0.99, P = 0.046), and insomnia (OR: 0.48, 95 % CI: 0.32-0.72, P < 0.001) than unvaccinated participants. There were no significant differences in psychiatric disorders between the vaccinated and unvaccinated groups during the Omicron BA.1/BA.2 period.

CONCLUSIONS: This is the first study to demonstrate that the associations between COVID-19 vaccination and post-COVID psychiatric disorders vary among the different variant periods. Future studies on these associations should be conducted with consideration to the prevalent circulating variants.}, } @article {pmid38354789, year = {2024}, author = {Giunta, S and Giordani, C and De Luca, M and Olivieri, F}, title = {Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging.}, journal = {Mechanisms of ageing and development}, volume = {218}, number = {}, pages = {111915}, doi = {10.1016/j.mad.2024.111915}, pmid = {38354789}, issn = {1872-6216}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Hypothalamo-Hypophyseal System/physiology ; Quality of Life ; Pituitary-Adrenal System/physiology ; *COVID-19 ; Chronic Disease ; Biomarkers ; Anti-Inflammatory Agents ; }, abstract = {The recently identified syndrome known as Long COVID (LC) is characterized by a constellation of debilitating conditions that impair both physical and cognitive functions, thus reducing the quality of life and increasing the risk of developing the most common age-related diseases. These conditions are linked to the presence of symptoms of autonomic dysfunction, in association with low cortisol levels, suggestive of reduced hypothalamic-pituitary-adrenal (HPA) axis activity, and with increased pro-inflammatory condition. Alterations of dopamine and serotonin neurotransmitter levels were also recently observed in LC. Interestingly, at least some of the proposed mechanisms of LC development overlap with mechanisms of Autonomic Nervous System (ANS) imbalance, previously detailed in the framework of the aging process. ANS imbalance is characterized by a proinflammatory sympathetic overdrive, and a concomitant decreased anti-inflammatory vagal parasympathetic activity, associated with reduced anti-inflammatory effects of the HPA axis and cholinergic anti-inflammatory pathway (CAP). These neuro-immune-endocrine system imbalanced activities fuel the vicious circle of chronic inflammation, i.e. inflammaging. Here, we refine our original hypothesis that ANS dysfunction fuels inflammaging and propose that biomarkers of ANS imbalance could also be considered biomarkers of inflammaging, recognized as the main risk factor for developing age-related diseases and the sequelae of viral infections, i.e. LC.}, } @article {pmid38353977, year = {2024}, author = {Harris, E}, title = {Millions of US Children Experience Range of Long COVID Effects.}, journal = {JAMA}, volume = {331}, number = {9}, pages = {726}, doi = {10.1001/jama.2024.0356}, pmid = {38353977}, issn = {1538-3598}, mesh = {Child ; Humans ; COVID-19/complications/diagnosis/epidemiology ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; United States/epidemiology ; }, } @article {pmid38353557, year = {2024}, author = {Titova, E and Kan, VW and Lozy, T and Ip, A and Shier, K and Prakash, VP and Starolis, M and Ansari, S and Goldgirsh, K and Kim, S and Pelliccia, MC and Mccutchen, A and Megalla, M and Gunning, TS and Kaufman, HW and Meyer, WA and Perlin, DS}, title = {Humoral and cellular immune responses against SARS-CoV-2 post-vaccination in immunocompetent and immunocompromised cancer populations.}, journal = {Microbiology spectrum}, volume = {12}, number = {3}, pages = {e0205023}, pmid = {38353557}, issn = {2165-0497}, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; COVID-19 Vaccines ; *Neoplasms ; Vaccination ; *Hematologic Neoplasms ; Immunity, Cellular ; Antibodies, Viral ; Immunity, Humoral ; *Spike Glycoprotein, Coronavirus ; }, abstract = {UNLABELLED: Cancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (n = 479) and immunocompromised individuals (n = 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or "Long-COVID"). Among immunocompromised individuals, 59% (n = 68) had an underlying hematologic malignancy; of those, 46% (n = 31) of individuals received cancer treatment <30 days prior to study blood collection. Ninety-eight percentage (n = 469) of immunocompetent and 81% (n = 93) of immunocompromised individuals had elevated RBD antibody titers (>1,000 U/mL), and of these, 60% (n = 281) and 44% (n = 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (n = 12) cohorts (P < 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes.

IMPORTANCE: The study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.}, } @article {pmid38353350, year = {2024}, author = {Wongwathanavikrom, NB and Tovichien, P and Udomittipong, K and Palamit, A and Tiamduangtawan, P and Mahoran, K and Charoensittisup, P}, title = {Incidence and risk factors for long COVID in children with COVID-19 pneumonia.}, journal = {Pediatric pulmonology}, volume = {59}, number = {5}, pages = {1330-1338}, doi = {10.1002/ppul.26910}, pmid = {38353350}, issn = {1099-0496}, support = {//None/ ; }, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Male ; Female ; Child ; Risk Factors ; Incidence ; SARS-CoV-2 ; Adolescent ; Child, Preschool ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Respiratory Function Tests ; Cough/etiology/epidemiology/physiopathology ; }, abstract = {BACKGROUND AND OBJECTIVE: There are only a few reports of long COVID including pulmonary function in children after COVID-19 pneumonia. We determined the incidence of long COVID and abnormal pulmonary function in those children and identify risk factors.

METHODS: This cohort study enrolled children admitted with COVID-19 pneumonia during 2021-2022. We gathered clinical characteristics during admission and at follow-up 3 months after.

RESULTS: We determined the incidence of long COVID at 39.7% (95% confidence interval [CI]: 30.7%-49.1%). All severe pneumonia cases consistently reported persistent symptoms. Exercise intolerance, cough, and fatigue were the three most common persistent symptoms in 26 (22.4%), 21 (18.1%), and 18 (15.5%) of the patients, respectively. At the follow-up, 21 cases (18.1%) demonstrated persistent abnormal chest radiographs. Three cases (6.9%) demonstrated restrictive ventilatory defects. Among those, one case (2.3%) demonstrated concomitant diffusion defect. Three cases (6.0%) demonstrated exercise-induced hypoxemia after the 6-minute walk test. Comparing spirometry variables between children with long COVID and without revealed significant difference of FEF25-75 (z score) between two groups. Age [adjusted OR (95% CI): 1.13 (1.05-1.22), p value 0.002], allergic diseases [adjusted OR (95% CI): 4.05 (1.36-12.06), p value 0.012], and living in polluted areas [adjusted OR (95% CI): 2.73 (1.18-6.33), p value 0.019] were significantly associated with long COVID.

CONCLUSION: A significant percentage of children developed long COVID after COVID-19 pneumonia. We should give additional attention to those who have exercise intolerance, chronic cough, or fatigue, especially older children, severe cases, children with allergic diseases, and those living in polluted areas.}, } @article {pmid38352809, year = {2024}, author = {Sawamura, T and Karashima, S and Kometani, M and Ohmori, A and Yoneda, T}, title = {Thyrotoxicosis Misdiagnosed as Long Covid by Telemedicine - A Cautionary Tale.}, journal = {European journal of case reports in internal medicine}, volume = {11}, number = {2}, pages = {004206}, pmid = {38352809}, issn = {2284-2594}, abstract = {INTRODUCTION: Individuals who have had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop post-coronavirus disease conditions, also known as long COVID. The symptoms of long COVID are nonspecific, and there are similarities between the symptoms of long COVID and those of Graves' disease (GD). Therefore, it is important to rule out GD in patients suspected of having long COVID. Telemedicine is widely used to avoid the risk of SARS-CoV-2 infection. However, owing to the lack of in-person examinations, diagnostic errors can occur.

CASE DESCRIPTION: A 27-year-old Japanese woman presented complaining of persistent fatigue, dyspnea, and low-grade fever, and after in-person examination was finally diagnosed with GD. She had been diagnosed with SARS-CoV-2 infection four months earlier and her symptoms had resolved within 5 days but then recurred. Subsequently, she had 3 telemedicine visits and had been diagnosed with long COVID.

DISCUSSION: With telemedicine there may be delayed diagnosis of GD in patients with a recent history of SARS-CoV-2 infection. Some symptoms and abnormalities cannot be confirmed in telemedicine visits performed using a simple mobile phone. Therefore it is important to know which findings obtained in telemedicine visits with a simple mobile phone are suggestive of GD. Low-grade fever and tachycardia are often observed in patients with GD, but rarely occur in patients with long COVID.

CONCLUSION: Tachycardia and persistent low-grade fever after SARS-CoV-2 infection, which can be confirmed by telemedicine, can be clues for the diagnosis of GD. Therefore, in-person examination should be added if these symptoms are confirmed by telemedicine.

LEARNING POINTS: The symptoms of Graves 'disease (GD) and long COVID may overlap.With telemedicine there may be delayed diagnosis of GD, in patients with recent history of severe acute respiratory syndrome mediated by coronavirus 2 (SARS-CoV-2) infections.In telemedicine visits, tachycardia and persistent low-grade fever could be clues for the diagnosis of GD after SARS-CoV-2 infections on telemedicine.}, } @article {pmid38352659, year = {2024}, author = {Isman, A and Nyquist, A and Strecker, B and Harinath, G and Lee, V and Zhang, X and Zalzala, S}, title = {Low-dose naltrexone and NAD+ for the treatment of patients with persistent fatigue symptoms after COVID-19.}, journal = {Brain, behavior, & immunity - health}, volume = {36}, number = {}, pages = {100733}, pmid = {38352659}, issn = {2666-3546}, abstract = {A subset of patients experiences persistent fatigue symptoms after COVID-19, and patients may develop long COVID, which is characterized by lasting systemic symptoms. No treatments for this condition have been validated and are urgently warranted. In this pilot study, we assessed whether treatment with low-dose naltrexone (LDN, 4.5 mg/day) and supplementation with NAD + through iontophoresis patches could improve fatigue symptoms and quality of life in 36 patients with persistent moderate/severe fatigue after COVID-19. We detected a significant increase from baseline in SF-36 survey scores after 12 weeks of treatment (mean total SF-36 score 36.5 [SD: 15.6] vs. 52.1 [24.8]; p < 0.0001), suggestive of improvement of quality of life. Furthermore, participants scored significantly lower on the Chalder fatigue scale after 12 weeks of treatment (baseline: 25.9 [4.6], 12 weeks: 17.4 [9.7]; p < 0.0001). We found a subset of 52 % of patients to be responders after 12 weeks of treatment. Treatment was generally safe, with mild adverse events previously reported for LDN, which could be managed with dose adjustments. The iontophoresis patches were associated with mild, short-lived skin irritation in 25 % of patients. Our data suggest treatment with LDN and NAD+ is safe and may be beneficial in a subset of patients with persistent fatigue after COVID-19. Larger randomized controlled trials will have to confirm our data and determine which patient subpopulations might benefit most from this strategy.}, } @article {pmid38351842, year = {2024}, author = {Colizzi, M and Comacchio, C and De Martino, M and Peghin, M and Bontempo, G and Chiappinotto, S and Fonda, F and Isola, M and Tascini, C and Balestrieri, M and Palese, A}, title = {COVID-19-induced neuropsychiatric symptoms can persist long after acute infection: a 2-year prospective study of biobehavioral risk factors and psychometric outcomes.}, journal = {Irish journal of psychological medicine}, volume = {}, number = {}, pages = {1-8}, doi = {10.1017/ipm.2023.53}, pmid = {38351842}, issn = {2051-6967}, abstract = {OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors.

METHODS: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools.

RESULTS: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels (OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up.

CONCLUSIONS: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.}, } @article {pmid38349116, year = {2024}, author = {Eltayeb, A and Al-Sarraj, F and Alharbi, M and Albiheyri, R and Mattar, EH and Abu Zeid, IM and Bouback, TA and Bamagoos, A and Uversky, VN and Rubio-Casillas, A and Redwan, EM}, title = {Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS-CoV-2 nucleocapsid protein and its liquid-liquid phase separation.}, journal = {Journal of cellular biochemistry}, volume = {125}, number = {3}, pages = {e30530}, doi = {10.1002/jcb.30530}, pmid = {38349116}, issn = {1097-4644}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Coronavirus Nucleocapsid Proteins ; Endothelial Cells ; Phase Separation ; Nucleocapsid Proteins ; }, abstract = {When the SARS-CoV-2 virus infects humans, it leads to a condition called COVID-19 that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE-2 protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three-fifths (~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long-term clinical studies in a group of people who contracted SARS-CoV-2 have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low-grade inflammation and often self-report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid-liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.}, } @article {pmid38348143, year = {2024}, author = {Schwendinger, F and Looser, VN and Gerber, M and Schmidt-Trucksäss, A}, title = {Autonomic dysfunction and exercise intolerance in post-COVID-19 - An as yet underestimated organ system?.}, journal = {International journal of clinical and health psychology : IJCHP}, volume = {24}, number = {1}, pages = {100429}, pmid = {38348143}, issn = {2174-0852}, abstract = {Individuals recovering from COVID-19 often present with persistent symptoms, particularly exercise intolerance and low cardiorespiratory fitness. Put simply, the Wasserman gear system describes the interdependence of heart, lungs, and musculature as determinants of cardiorespiratory fitness. Based on this system, recent findings indicate a contribution of peripheral, cardiovascular, and lung diffusion limitations to persistent symptoms of exercise intolerance and low cardiorespiratory fitness. The autonomic nervous system as an organ system involved in the pathophysiology of exercise intolerance and low cardiorespiratory fitness, has received only little attention as of yet. Hence, our article discusses contribution of the autonomic nervous system through four potential pathways, namely alterations in (1) cerebral hemodynamics, (2) afferent and efferent signaling, (3) central hypersensitivity, and (4) appraisal and engagement in physical activity. These pathways are summarized in a psycho-pathophysiological model. Consequently, this article encourages a shift in perspective by examining the state of the pulmonary and cardiovascular system, the periphery, and auxiliary, the autonomic nervous system as potential underlying mechanisms for exercise intolerance and low cardiorespiratory fitness in patients with post-COVID-19.}, } @article {pmid38347167, year = {2024}, author = {Lui, DTW and Lee, CH and Woo, YC and Hung, IFN and Lam, KSL}, title = {Thyroid dysfunction in COVID-19.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {6}, pages = {336-348}, pmid = {38347167}, issn = {1759-5037}, mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; *Thyroid Diseases/epidemiology/physiopathology ; *SARS-CoV-2 ; COVID-19 Vaccines ; Thyroid Gland/physiopathology ; }, abstract = {The COVID-19 pandemic has affected over 772 million people globally. While lung damage is the major contributor to the morbidity and mortality of this disease, the involvement of multiple organs, including the endocrine glands, has been reported. This Review aims to provide an updated summary of evidence regarding COVID-19 and thyroid dysfunction, incorporating highlights of recent advances in the field, particularly in relation to long COVID and COVID-19 vaccination. Since subacute thyroiditis following COVID-19 was first reported in May 2020, thyroid dysfunction associated with COVID-19 has been increasingly recognized, secondary to direct and indirect effects on the hypothalamic-pituitary-thyroid axis. Here, we summarize the epidemiological evidence, pattern and clinical course of thyroid dysfunction following COVID-19 and examine radiological, molecular and histological evidence of thyroid involvement in SARS-CoV-2 infection. Beyond acute SARS-CoV-2 infection, it is also timely to examine the course and implication of thyroid dysfunction in the context of long COVID owing to the large population of survivors of COVID-19 worldwide. This Review also analyses the latest evidence on the relationship between the therapeutics and vaccination for COVID-19 and thyroid dysfunction. To conclude, evidence-based practice recommendations for thyroid function testing during and following COVID-19 and concerning COVID-19 vaccination are proposed.}, } @article {pmid38346773, year = {2024}, author = {Jamieson, A and Al Saikhan, L and Alghamdi, L and Hamill Howes, L and Purcell, H and Hillman, T and Heightman, M and Treibel, T and Orini, M and Bell, R and Scully, M and Hamer, M and Chaturvedi, N and Montgomery, H and Hughes, AD and Astin, R and Jones, S}, title = {Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction.}, journal = {Physiological reports}, volume = {12}, number = {3}, pages = {e15940}, pmid = {38346773}, issn = {2051-817X}, support = {MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Male ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19/metabolism ; Muscle, Skeletal/metabolism ; Exercise/physiology ; Exercise Test/methods ; Exercise Tolerance/physiology ; Oxygen Consumption/physiology ; }, abstract = {The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ("long COVID") is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.}, } @article {pmid38346670, year = {2024}, author = {Takamatsu, A and Honda, H and Miwa, T and Tabuchi, T and Taniguchi, K and Shibuya, K and Tokuda, Y}, title = {Prevalence and trends in persistent symptoms following COVID-19 in Japan: A nationwide cross-sectional survey.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {30}, number = {8}, pages = {725-733}, doi = {10.1016/j.jiac.2024.02.008}, pmid = {38346670}, issn = {1437-7780}, mesh = {Humans ; *COVID-19/epidemiology ; Japan/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Prevalence ; Middle Aged ; Adult ; Aged ; *SARS-CoV-2 ; Surveys and Questionnaires ; Back Pain/epidemiology ; Young Adult ; }, abstract = {INTRODUCTION: Even during the endemic phase of the COVID-19 pandemic, the impact of persistent symptoms on patients and healthcare systems remains significant. Thus, a more comprehensive understanding of these symptoms is essential.

METHODS: Using data from the Japan Society and New Tobacco Internet Survey conducted in February 2023, this cross-sectional study investigated the prevalence of, and changes in, persistent COVID-19 symptoms.

RESULTS: In total, 21,108 individuals responded to the survey. Of these, 29.1 % (6143) had a history of COVID-19. Our analysis found that arm/leg/joint pain (adjusted odds ratio [aOR]: 1.17; 95 % confidence interval [95 % CI]: 1.03-1.33), back pain (aOR: 1.13; 95 % CI: 1.01-1.27), chest pain (aOR: 1.53; 95 % CI: 1.20-1.96), malaise (aOR: 1.14; 95 % CI: 1.02-1.28), loss of taste (aOR: 2.55; 95 % CI: 1.75-3.72), loss of smell (aOR: 2.33; 95 % CI: 1.67-3.26), memory impairment (aOR: 1.27; 95 % CI: 1.04-1.56), and cough (aOR: 1.72; 95 % CI: 1.38-2.13) were independently associated with a history of COVID-19 contracted more than two months but less than six months previously. Further, back pain (aOR: 1.24; 95 % CI: 1.04-1.47) and loss of taste (aOR: 2.28; 95 % CI: 1.24-4.21) showed independent association with COVID-19 contracted more than 12 months previously.

CONCLUSIONS: Various symptoms were independently associated with a history of COVID-19. While most patients tend to recover within a year after contracting COVID-19, certain symptoms, such as back pain and loss of taste, persist longer than a year, underscoring public health concerns and emphasizing the need for health care services to support patients suffering from persistent symptoms.}, } @article {pmid38344131, year = {2024}, author = {Shen, Y and Robertson, MM and Kulkarni, SG and Puzniak, L and Zamparo, JM and Allen, KE and Porter, TM and Qasmieh, SA and Grov, C and Srivastava, A and Zimba, R and McLaughlin, JM and Nash, D}, title = {Oral COVID-19 Antiviral Uptake Among a Highly Vaccinated US Cohort of Adults With SARS-CoV-2 Infection Between December 2021 and October 2022.}, journal = {Open forum infectious diseases}, volume = {11}, number = {2}, pages = {ofad674}, pmid = {38344131}, issn = {2328-8957}, support = {P2C HD050924/HD/NICHD NIH HHS/United States ; UH3 AI133675/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022.

METHODS: We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID).

RESULTS: NMV/r uptake was 13.6% (95% CI, 11.9%-15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%-2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%-2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%-20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%-29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%-12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%-13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P = .001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%-70%) reported that NMV/r was helpful for reducing COVID-19 symptoms.

CONCLUSIONS: Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed.}, } @article {pmid38343863, year = {2024}, author = {Preiss, A and Bhatia, A and Aragon, LV and Baratta, JM and Baskaran, M and Blancero, F and Brannock, MD and Chew, RF and Diaz, I and Fitzgerald, M and Kelly, EP and Zhou, AG and Carton, TW and Chute, CG and Haendel, M and Moffitt, R and Pfaff, E and , and , }, title = {Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.20.24301525}, pmid = {38343863}, support = {UL1 TR002548/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, abstract = {Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters, which suggests that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms.}, } @article {pmid38343619, year = {2024}, author = {Li, Y and Lam, LT and Xiao, Y and Qiu, Z and Zhang, Y}, title = {The association between Long-COVID symptomology, perceived symptom burden and mental health in COVID-19 patients in Shijiazhuang, China: a population-based health survey.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1332066}, pmid = {38343619}, issn = {1664-0640}, abstract = {BACKGROUND: Long-COVID (LC) refers to post-acute COVID-19 symptoms that can last for months or longer after the initial infection, affecting the physical health of infected patients. This study aims to investigate the association between the symptomology of LC and the mental health of patients in China. It also aims to examine the relationship between the perceived symptom burden and mental health of these patients.

METHODS: A population-based stratified cluster sample was recruited, using a standard sampling procedure, from a prefecture-level city in Northern China. Participants included patients who had tested positive for COVID-19 after December 2022. LC symptomology was assessed using a LC symptoms checklist where the perceived symptom burden was measured by the included 5-point Likert scales. Mental health of patients was measured using the Depression, Anxiety, and Stress Scale (DASS), the original Connor-Davidson Resilience Scale (CD-RISC), and the Duke-UNC Functional Social Support Questionnaire (DUFSS). Data were analysed using multiple linear regression models.

RESULTS: About 25% of respondents, experienced COVID symptoms lasting longer than two months that could only be explained by the infection. Post-exertional malaise (22.2%) and fatigue (21.2%) were the most common symptoms. After controlling for potential confounding variables, LC symptomology was significantly and positively associated with depression (t=2.09, p=0.037) and anxiety (t=4.51, p<0.001), but not stress. Perceived symptoms burden was also positively and significantly related to depression (β=0.35, p<0.001), anxiety (β=0.54, p<0.001), and stress (β=0.35, p<0.001), suggesting a dose-response relationship between perceived symptom burden and mental ill health.

CONCLUSION: This study highlights the importance of recognising the risk of LC, patients' perception of the symptom burden and its potential impact on mental health. Healthcare professionals should be aware of the complexity of psychological comorbidities among infected patients reporting prolonged symptoms, and be able to give advice regarding long-term management of the symptoms.}, } @article {pmid38343432, year = {2024}, author = {Sivan, M and Heightman, M}, title = {A New Professional Society for Post-COVID Condition and Other Post-Viral Conditions.}, journal = {Advances in rehabilitation science and practice}, volume = {13}, number = {}, pages = {27536351241231351}, pmid = {38343432}, issn = {2753-6351}, } @article {pmid38343427, year = {2024}, author = {Cuschieri, S and Wilk, P}, title = {Does Pre-existing Diabetes Correlate with Long COVID-19 in Europe? Evidence from the Analysis of the Survey of Health, Ageing and Retirement in Europe's Corona Surveys.}, journal = {Journal of diabetes research}, volume = {2024}, number = {}, pages = {7459628}, pmid = {38343427}, issn = {2314-6753}, mesh = {Middle Aged ; Humans ; Female ; Aged ; Male ; Retirement ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/epidemiology ; Aging ; *Diabetes Mellitus/epidemiology ; Surveys and Questionnaires ; *Hypertension/epidemiology ; Europe/epidemiology ; }, abstract = {BACKGROUND: A substantial proportion of those infected with COVID-19 are presenting with persistent symptoms, referred to as long COVID-19. Emerging evidence suggests that the presence of pre-existing chronic conditions, such as diabetes, may increase the risk of long COVID-19.

OBJECTIVES: To investigate whether having pre-existing diabetes increases the risk of developing long COVID-19 in the population of middle-aged and older adults (≥50 years old) in Europe, while assessing if this relationship can be accounted for or is modified by the known long COVID-19 and diabetes risk factors (age, sex, hospitalization, pre-existing hypertension, and weight status).

METHODS: A population-based longitudinal prospective study involving a sample of respondents aged 50 years and older (n = 4,004) with probable or confirmed COVID-19 infection from 27 countries that participated in both waves 7 and 8 of the Survey of Health, Ageing and Retirement in Europe and its 2020 and 2021 Corona Surveys. Logistic regression modeling was performed.

RESULTS: Overall, 66.8% of the respondents affected by COVID-19 infection reported at least one long COVID-19 symptom; 55.2% were female, and the average age was 64.6 years; 13.2% had pre-existing diabetes. Respondents with pre-existing diabetes had significantly higher odds of developing long COVID-19, compared to those without diabetes (OR = 1.37; 95% CI = 1.12, 1.68). This relationship remained significant (OR = 2.00; 98% CI = 0.25, 1.14) after adjusting for sex (OR = 1.64 for females; 95% CI = 1.43, 1.88), hospitalization for COVID-19 illness (OR = 3.19; 95% CI = 2.41, 4.23), pre-existing hypertension (OR = 1.17; 95% CI = 1.01, 1.36), and overweight (OR = 1.31; 95% CI = 1.11, 1.56) and obese (OR = 1.77; 95% CI = 1.44, 2.19) weight status. The effect of pre-existing diabetes on the risk of long COVID-19 is moderated by age; it was highest at the age of 50 (OR = 2.00; 95% CI = 1.28, 3.14), and then, it declined with age.

CONCLUSIONS: There is a relationship between pre-existing diabetes and long COVID-19, even after controlling for literature-based confounding factors, with age having a moderating effect on this relationship.}, } @article {pmid38342941, year = {2024}, author = {Rogn, Å and Jensen, JL and Iversen, PO and Singh, PB}, title = {Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {3455}, pmid = {38342941}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Ageusia/etiology ; Anosmia ; Cross-Sectional Studies ; SARS-CoV-2 ; Dysgeusia/epidemiology/etiology ; *Olfaction Disorders/etiology/complications ; Smell ; }, abstract = {Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations.}, } @article {pmid38341566, year = {2024}, author = {Zhang, Y and Romieu-Hernandez, A and Boehmer, TK and Azziz-Baumgartner, E and Carton, TW and Gundlapalli, AV and Fearrington, J and Nagavedu, K and Dea, K and Moyneur, E and Cowell, LG and Kaushal, R and Mayer, KH and Puro, J and Rasmussen, SA and Thacker, D and Weiner, MG and Saydah, S and Block, JP and , }, title = {Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {181}, pmid = {38341566}, issn = {1471-2334}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; 6-NU38OT000316/CC/CDC HHS/United States ; OTA HL161847-01/NH/NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; *Diabetes Mellitus, Type 2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; }, abstract = {BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results.

METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test.

RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions.

CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.}, } @article {pmid38341321, year = {2024}, author = {Barion, BG and Rocha, TRFD and Ho, YL and Mazetto Fonseca, BM and Okazaki, E and Rothschild, C and Stefanello, B and Rocha, VG and Villaça, PR and Orsi, FA}, title = {Extracellular vesicles are a late marker of inflammation, hypercoagulability and COVID-19 severity.}, journal = {Hematology, transfusion and cell therapy}, volume = {46}, number = {2}, pages = {176-185}, pmid = {38341321}, issn = {2531-1387}, abstract = {Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31[+], EV-CD41[+] and EV-CD142[+] levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19.}, } @article {pmid38341012, year = {2024}, author = {Dirajlal-Fargo, S and Maison, DP and Durieux, JC and Andrukhiv, A and Funderburg, N and Ailstock, K and Gerschenson, M and Mccomsey, GA}, title = {Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection.}, journal = {Mitochondrion}, volume = {75}, number = {}, pages = {101849}, pmid = {38341012}, issn = {1872-8278}, support = {P20 GM113134/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Respiration ; Disease Progression ; Adenosine Triphosphate ; }, abstract = {Peripheral blood mononuclear cells (PBMC) mitochondrial respiration was measured ex vivo from participants without a history of COVID (n = 19), with a history of COVID and full recovery (n = 20), and with PASC (n = 20). Mean mitochondrial basal respiration, ATP-linked respiration, maximal respiration, spare respiration capacity, ATP-linked respiration, and non-mitochondrial respiration were highest in COVID + PASC+ (p ≤ 0.04). Every unit increase in non-mitochondrial respiration, ATP-linked respiration, basal respiration, spare respiration capacity, and maximal respiration increased the predicted odds of PASC between 1 % and 6 %. Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.}, } @article {pmid38340875, year = {2024}, author = {Zhang, X and Li, F and Rajaraman, PK and Comellas, AP and Hoffman, EA and Lin, CL}, title = {Investigating distributions of inhaled aerosols in the lungs of post-COVID-19 clusters through a unified imaging and modeling approach.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {195}, number = {}, pages = {106724}, pmid = {38340875}, issn = {1879-0720}, support = {R01 HL168116/HL/NHLBI NIH HHS/United States ; S10 RR022421/RR/NCRR NIH HHS/United States ; U01 HL114494/HL/NHLBI NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Respiratory Aerosols and Droplets ; Lung/diagnostic imaging ; *Asthma/drug therapy ; Administration, Inhalation ; Particle Size ; }, abstract = {BACKGROUND: Recent studies, based on clinical data, have identified sex and age as significant factors associated with an increased risk of long COVID. These two factors align with the two post-COVID-19 clusters identified by a deep learning algorithm in computed tomography (CT) lung scans: Cluster 1 (C1), comprising predominantly females with small airway diseases, and Cluster 2 (C2), characterized by older individuals with fibrotic-like patterns. This study aims to assess the distributions of inhaled aerosols in these clusters.

METHODS: 140 COVID survivors examined around 112 days post-diagnosis, along with 105 uninfected, non-smoking healthy controls, were studied. Their demographic data and CT scans at full inspiration and expiration were analyzed using a combined imaging and modeling approach. A subject-specific CT-based computational model analysis was utilized to predict airway resistance and particle deposition among C1 and C2 subjects. The cluster-specific structure and function relationships were explored.

RESULTS: In C1 subjects, distinctive features included airway narrowing, a reduced homothety ratio of daughter over parent branch diameter, and increased airway resistance. Airway resistance was concentrated in the distal region, with a higher fraction of particle deposition in the proximal airways. On the other hand, C2 subjects exhibited airway dilation, an increased homothety ratio, reduced airway resistance, and a shift of resistance concentration towards the proximal region, allowing for deeper particle penetration into the lungs.

CONCLUSIONS: This study revealed unique mechanistic phenotypes of airway resistance and particle deposition in the two post-COVID-19 clusters. The implications of these findings for inhaled drug delivery effectiveness and susceptibility to air pollutants were explored.}, } @article {pmid38339115, year = {2024}, author = {Bielecka, E and Sielatycki, P and Pietraszko, P and Zapora-Kurel, A and Zbroch, E}, title = {Elevated Arterial Blood Pressure as a Delayed Complication Following COVID-19-A Narrative Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339115}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Arterial Pressure ; Angiotensin-Converting Enzyme Inhibitors ; Renin-Angiotensin System ; *Hypertension ; Blood Pressure/physiology ; }, abstract = {Arterial hypertension is one of the most common and significant cardiovascular risk factors. There are many well-known and identified risk factors for its development. In recent times, there has been growing concern about the potential impact of COVID-19 on the cardiovascular system and its relation to arterial hypertension. Various theories have been developed that suggest a connection between COVID-19 and elevated blood pressure. However, the precise link between SARS-CoV-2 infection and the long-term risk of developing hypertension remains insufficiently explored. Therefore, the primary objective of our study was to investigate the influence of COVID-19 infection on blood pressure elevation and the subsequent risk of developing arterial hypertension over an extended period. To accomplish this, we conducted a thorough search review of relevant papers in the PubMed and SCOPUS databases up to 3 September 2023. Our analysis encompassed a total of 30 eligible articles. Out of the 30 papers we reviewed, 19 of them provided substantial evidence showing a heightened risk of developing arterial hypertension following COVID-19 infection. Eight of the studies showed that blood pressure values increased after the infection, while three of the qualified studies did not report any notable impact of COVID-19 on blood pressure levels. The precise mechanism behind the development of hypertension after COVID-19 remains unclear, but it is suggested that endothelial injury and dysfunction of the renin-angiotensin-aldosterone system may be contributory. Additionally, changes in blood pressure following COVID-19 infection could be linked to lifestyle alterations that often occur alongside the illness. Our findings emphasize the pressing requirement for thorough research into the relationship between COVID-19 and hypertension. These insights are essential for the development of effective prevention and management approaches for individuals who have experienced COVID-19 infection.}, } @article {pmid38338803, year = {2024}, author = {Ansone, L and Rovite, V and Brīvība, M and Jagare, L and Pelcmane, L and Borisova, D and Thews, A and Leiminger, R and Kloviņš, J}, title = {Longitudinal NMR-Based Metabolomics Study Reveals How Hospitalized COVID-19 Patients Recover: Evidence of Dyslipidemia and Energy Metabolism Dysregulation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38338803}, issn = {1422-0067}, support = {1.1.1.1/21/A/029//European Regional Development Fund/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Energy Metabolism ; *Dyslipidemias ; }, abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint of recovering severe COVID-19 patients at three consecutive timepoints and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post-hospitalization.}, } @article {pmid38338174, year = {2024}, author = {Costanza, A and Amerio, A and Aguglia, A and Magnani, L and Alexander, J and Maiorano, A and Richard-Lepouriel, H and Portacolone, E and Berardelli, I and Pompili, M and Serafini, G and Amore, M and Nguyen, KD}, title = {A Prospective Multicenter Longitudinal Analysis of Suicidal Ideation among Long-COVID-19 Patients.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {38338174}, issn = {2227-9032}, abstract = {Long coronavirus disease 19 (COVID-19) is an emerging multifaceted illness with the pathological hallmarks of chronic inflammation and neuropsychiatric symptoms. These pathologies have also been implicated in developing suicidal behaviors and suicidal ideation (SI). However, research addressing suicide risk in long COVID-19 is limited. In this prospective study, we aim to characterize SI development among long-COVID-19 patients and to determine the predictive power of inflammatory markers and long-COVID-19 symptoms-including those of psychiatric origin-for SI. During this prospective, longitudinal, multicenter study, healthy subjects and long-COVID-19 patients will be recruited from the University Hospital of Geneva, Switzerland, the University of Genova, the University of Rome "La Sapienza", and the University of San Francisco. Study participants will undergo a series of clinic visits over a follow-up period of 1 year for SI assessment. Baseline and SI-onset levels of inflammatory mediators in plasma samples, along with 12 long-COVID-19 features (post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal disturbance, palpitations, changes in sexual desire/capacity, loss/change of smell/taste, thirst, chronic cough, chest pain, and abnormal movements) will be collected for SI risk analysis. The proposed enrollment period is from 15 January 2024 to 15 January 2026 with targeted recruitment of 100 participants for each study group. The anticipated findings of this study are expected to provide important insights into suicide risk among long-COVID-19 patients and determine whether inflammation and psychiatric comorbidities are involved in the development of SI in these subjects. This could pave the way to more effective evidence-based suicide prevention approaches to address this emerging public health concern.}, } @article {pmid38337760, year = {2024}, author = {Negrut, N and Menegas, G and Kampioti, S and Bourelou, M and Kopanyi, F and Hassan, FD and Asowed, A and Taleouine, FZ and Ferician, A and Marian, P}, title = {The Multisystem Impact of Long COVID: A Comprehensive Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {38337760}, issn = {2075-4418}, abstract = {(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: the recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.}, } @article {pmid38337533, year = {2024}, author = {Tański, W and Tomasiewicz, A and Jankowska-Polańska, B}, title = {Sleep Disturbances as a Consequence of Long COVID-19: Insights from Actigraphy and Clinimetric Examinations-An Uncontrolled Prospective Observational Pilot Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {3}, pages = {}, pmid = {38337533}, issn = {2077-0383}, abstract = {The COVID-19 pandemic represents a global health and social challenge. However, the impact of a SARS-CoV-2 infection itself on mental health and sleep quality remains poorly understood. The purpose of the present uncontrolled prospective observational pilot study was to evaluate the impact of past COVID-19 disease on the incidence of quantitative and qualitative sleep disturbances. A group of 61 subjects (37 female, 24 male) reported sleep disturbances that had lasted for at least one month and had started after recovery from COVID-19. The study used self-reported instruments: the Epworth Sleepiness Scale (ESS) and Insomnia Severity Index (ISI), as well as an objective method-actigraphy-for quantitative analysis of sleep architecture. It was shown that sleep disturbances most commonly started after recovery (68.3%, n = 41) and lasted for more than one month (83.6%, n = 51). ESS scores of 7.8 ± 5.0 points indicate moderate daytime sleepiness, and ISI scores of 16.3 ± 5.8 points denote moderate insomnia. ESS scores were negatively correlated with total time in bed (r = -0.3780, p = 0.003), total sleep time (r = -0.2969, p = 0.020), and wakefulness after sleep onset (r = -0.2654, p = 0.039). In addition, ESS scores were correlated negatively with the respondents' age (B = -0.17, p = 0.000) and time from COVID-19 onset. A positive correlation was found between wakefulness after sleep onset and ESS scores (B = -0.05, p = 0.039). ISI scores were positively correlated with time in bed (r = 0.3275, p = 0.010). Female gender was found to be a significant predictor of insomnia's severity (B = 2.159, t = 3.04, p = 0.004). In conclusion, patients with a history of COVID-19 report long-lasting sleep disturbances that do not subside spontaneously. In the patient group studied, moderate levels of daytime sleepiness and insomnia were found. The most frequently reported problems included irregular sleep, frequent awakenings, and difficulty maintaining sleep, while normal sleep duration was preserved. These findings underscore the need for continued attention to the long-term consequences of COVID-19 on sleep health and emphasize the importance of targeted interventions to address these enduring sleep disturbances in affected individuals.}, } @article {pmid38336892, year = {2024}, author = {Hamrefors, V and Kahn, F and Holmqvist, M and Carlson, K and Varjus, R and Gudjonsson, A and Fedorowski, A and Ohlsson, B}, title = {Gut microbiota composition is altered in postural orthostatic tachycardia syndrome and post-acute COVID-19 syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {3389}, pmid = {38336892}, issn = {2045-2322}, support = {501100003173//Crafoordska Stiftelsen (Crafoord Foundation)/ ; }, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis ; *Irritable Bowel Syndrome/complications ; *Gastrointestinal Microbiome ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; }, abstract = {Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.}, } @article {pmid38336381, year = {2024}, author = {Mone, P and Jankauskas, SS and Manzi, MV and Gambardella, J and Coppola, A and Kansakar, U and Izzo, R and Fiorentino, G and Lombardi, A and Varzideh, F and Sorriento, D and Trimarco, B and Santulli, G}, title = {Endothelial Extracellular Vesicles Enriched in microRNA-34a Predict New-Onset Diabetes in Coronavirus Disease 2019 (COVID-19) Patients: Novel Insights for Long COVID Metabolic Sequelae.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {389}, number = {1}, pages = {34-39}, pmid = {38336381}, issn = {1521-0103}, support = {R01 DK123259/DK/NIDDK NIH HHS/United States ; R01 DK033823/DK/NIDDK NIH HHS/United States ; R01 HL159062/HL/NHLBI NIH HHS/United States ; R01 HL146691/HL/NHLBI NIH HHS/United States ; T32 HL144456/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Endothelial Cells ; *Diabetes Mellitus ; Disease Progression ; *MicroRNAs ; *Hypertension ; *Dyslipidemias ; }, abstract = {Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an increased risk of developing new-onset diabetes. However, the mechanisms underlying this association are mostly unknown, and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. SIGNIFICANCE STATEMENT: We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing diabetes after having contracted coronavirus disease 2019 (COVID-19). This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (long COVID).}, } @article {pmid38336025, year = {2024}, author = {Duindam, HB and Mengel, D and Kox, M and Göpfert, JC and Kessels, RPC and Synofzik, M and Pickkers, P and Abdo, WF}, title = {Systemic inflammation relates to neuroaxonal damage associated with long-term cognitive dysfunction in COVID-19 patients.}, journal = {Brain, behavior, and immunity}, volume = {117}, number = {}, pages = {510-520}, doi = {10.1016/j.bbi.2024.02.002}, pmid = {38336025}, issn = {1090-2139}, mesh = {Humans ; Middle Aged ; Longitudinal Studies ; Prospective Studies ; *COVID-19/complications ; *Cognitive Dysfunction ; Inflammation ; Dexamethasone ; }, abstract = {BACKGROUND AND OBJECTIVES: Cognitive deficits are increasingly recognized as a long-term sequela of severe COVID-19. The underlying processes and molecular signatures associated with these long-term neurological sequalae of COVID-19 remain largely unclear, but may be related to systemic inflammation-induced effects on the brain. We studied the systemic inflammation-brain interplay and its relation to development of long-term cognitive impairment in patients who survived severe COVID-19. Trajectories of systemic inflammation and neuroaxonal damage blood biomarkers during ICU admission were analyzed and related to long-term cognitive outcomes.

METHODS: Prospective longitudinal cohort study of patients with severe COVID-19 surviving ICU admission. During admission, blood was sampled consecutively to assess levels of inflammatory cytokines and neurofilament light chain (NfL) using an ultrasensitive multiplex Luminex assay and single molecule array technique (Simoa). Cognitive functioning was evaluated using a comprehensive neuropsychological assessment six months after ICU-discharge.

RESULTS: Ninety-six patients (median [IQR] age 61 [55-69] years) were enrolled from March 2020 to June 2021 and divided into two cohorts: those who received no COVID-19-related immunotherapy (n = 28) and those treated with either dexamethasone or dexamethasone and tocilizumab (n = 68). Plasma NfL concentrations increased in 95 % of patients during their ICU stay, from median [IQR] 23 [18-38] pg/mL at admission to 250 [160-271] pg/mL after 28 days, p < 0.001. Besides age, glomerular filtration rate, immunomodulatory treatment, and C-reactive protein, more specific markers of systemic inflammation at day 14 (i.e., interleukin (IL)-8, tumour necrosis factor, and IL-1 receptor antagonist) were significant predictors of blood NfL levels at day 14 of ICU admission (R[2] = 44 %, p < 0.001), illustrating the association between sustained systemic inflammation and neuroaxonal damage. Twenty-six patients (27 %) exhibited cognitive impairment six months after discharge from the ICU. NfL concentrations showed a more pronounced increase in patients that developed cognitive impairment (p = 0.03). Higher NfL predicted poorer outcome in information processing speed (Trail Making Test A, r = -0.26, p = 0.01; Letter Digit Substitution Test, r = -0.24, p = 0.02).

DISCUSSION: Prolonged systemic inflammation in critically ill COVID-19 patients is related to neuroaxonal damage and subsequent long-term cognitive impairment. Moreover, our findings suggest that plasma NfL concentrations during ICU stay may possess prognostic value in predicting future long-term cognitive impairment in patients that survived severe COVID-19.}, } @article {pmid38335908, year = {2024}, author = {Bronowicka-Szydełko, A and Gostomska-Pampuch, K and Kuzan, A and Pietkiewicz, J and Krzystek-Korpacka, M and Gamian, A}, title = {Effect of advanced glycation end-products in a wide range of medical problems including COVID-19.}, journal = {Advances in medical sciences}, volume = {69}, number = {1}, pages = {36-50}, doi = {10.1016/j.advms.2024.01.003}, pmid = {38335908}, issn = {1898-4002}, mesh = {*Glycation End Products, Advanced/metabolism ; Humans ; *COVID-19/metabolism/virology ; *SARS-CoV-2/isolation & purification/metabolism ; Diabetes Complications/metabolism ; Atherosclerosis/metabolism ; Neurodegenerative Diseases/metabolism ; }, abstract = {Glycation is a physiological process that determines the aging of the organism, while in states of metabolic disorders it is significantly intensified. High concentrations of compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example in diabetes, atherosclerosis, dyslipidemia, obesity or metabolic syndrome, lead to increased glycation of proteins, lipids and nucleic acids. The level of advanced glycation end-products (AGEs) in the body depends on rapidity of their production and the rate of their removal by the urinary system. AGEs, accumulated in the extracellular matrix of the blood vessels and other organs, cause irreversible changes in the biochemical and biomechanical properties of tissues. As a consequence, micro- and macroangiopathies appear in the system, and may contribute to the organ failure, like kidneys and heart. Elevated levels of AGEs also increase the risk of Alzheimer's disease and various cancers. In this paper, we propose a new classification due to modified amino acid residues: arginyl-AGEs, monolysyl-AGEs and lysyl-arginyl-AGEs and dilysyl-AGEs. Furthermore, we describe in detail the effect of AGEs on the pathogenesis of metabolic and old age diseases, such as diabetic complications, atherosclerosis and neurodegenerative diseases. We summarize the currently available data on the diagnostic value of AGEs and present the AGEs as a therapeutic goal in a wide range of medical problems, including SARS-CoV-2 infection and so-called long COVID.}, } @article {pmid38335408, year = {2024}, author = {Dong, J and Ni, J and Zhang, Z and Yan, H and Xu, J and Zhao, J}, title = {The impact of "long COVID" on menstruation in Chinese female college students and the intervention of acupuncture.}, journal = {Medicine}, volume = {103}, number = {6}, pages = {e36818}, pmid = {38335408}, issn = {1536-5964}, mesh = {Female ; Humans ; Menstruation ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/therapy ; *Acupuncture Therapy ; Students ; China/epidemiology ; Menstruation Disturbances/epidemiology/therapy ; }, abstract = {This study aimed to explore the potential application value of acupuncture in alleviating the impact of long COVID on women's menstrual cycles, by investigating the occurrence of long COVID among female college students, its effects on menstruation, and the intervention of acupuncture. This cross-sectional study surveyed female college students with a history of coronavirus disease 2019 (COVID-19) before April 10, 2023. A questionnaire was used to analyze demographic characteristics, post-COVID sequelaes, duration of symptoms, and treatments received during that period. Among the 731 participants enrolled in the survey, 468 were female undergraduate students who met the analysis criteria. Among them, 85 individuals fit the definition of "Long COVID" (18.16%). Within the group of patients with long COVID, 69 individuals experienced changes in their overall menstrual patterns compared to the 6 months prior to contracting the novel coronavirus (81.18%). Additionally, 17 individuals opted for acupuncture treatment following the onset of COVID-19 (20.00%), which resulted in less impact on their menstrual cycle (41.18% vs 64.71% without receiving acupuncture, OR = 2.62), menstrual period duration (41.18% vs 64.71%, OR = 2.62), menstrual flow (47.06% vs 69.18%, OR = 2.52), and the color of menstrual blood (41.18% vs 63.24%, OR = 2.46) among these patients. Long COVID had a certain impact on menstruation. Acupuncture potentially alleviates the clinical symptoms of long COVID and reduces its impact on women's menstrual cycle, thus having potential therapeutic value in the treatment of long COVID.}, } @article {pmid38334972, year = {2024}, author = {Longobardi, I and Prado, DMLD and de Andrade, DCO and Goessler, KF and de Oliveira Júnior, GN and de Almeida Azevedo, R and Leitão, AE and Santos, JVP and Pinto, ALS and Gualano, B and Roschel, H}, title = {Cardiorespiratory abnormalities in ICU survivors of COVID-19 with postacute sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {326}, number = {4}, pages = {H907-H915}, doi = {10.1152/ajpheart.00073.2024}, pmid = {38334972}, issn = {1522-1539}, support = {#2021/13580-1//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; #2019/18039-7//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; #2020/07540-4//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; Finance Code 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; #88887.700422/2022-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; #2017/13552-2//Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)/ ; #308307/2021-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; }, mesh = {Female ; Male ; Humans ; *COVID-19 ; SARS-CoV-2 ; Cross-Sectional Studies ; Respiration, Artificial ; Disease Progression ; Intensive Care Units ; Oxygen ; }, abstract = {Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) often leads to exertional intolerance and reduced exercise capacity, particularly in individuals previously admitted to an intensive care unit (ICU). However, the impact of invasive mechanical ventilation (IMV) on PASC-associated cardiorespiratory abnormalities during exercise remains poorly understood. This single-center, cross-sectional study aimed to gather knowledge on this topic. Fifty-two patients with PASC recruited ∼6 mo after ICU discharge were clustered based on their need for IMV (PASC + IMV, n = 27) or noninvasive support therapy (PASC + NIS, n = 25). Patients underwent pulmonary function and cardiopulmonary exercise testing (CPX) and were compared with a reference group (CONTROL, n = 19) comprising individuals of both sexes with similar age, comorbidities, and physical activity levels but without a history of COVID-19 illness. Individuals with PASC, irrespective of support therapy, presented with higher rates of cardiorespiratory abnormalities than CONTROL, especially dysfunctional breathing patterns, dynamic hyperinflation, reduced oxygen uptake and oxygen pulse, and blunted heart rate recovery (all P < 0.05). Only the rate of abnormal oxygen pulse was greater among PASC + IMV group than PASC + NIS group (P = 0.05). Mean estimates for all CPX variables were comparable between PASC + IMV and PASC + NIS groups (all P > 0.05). These findings indicate significant involvement of both central and peripheral factors, leading to exertional intolerance in individuals with PASC previously admitted to the ICU, regardless of their need for IMV.NEW & NOTEWORTHY We found cardiorespiratory abnormalities in ICU survivors of severe-to-critical COVID-19 with PASC to be independent of IMV need. Overall, both group of patients experienced dysfunctional breathing patterns, dynamic hyperinflation, lower oxygen uptake and oxygen pulse, and blunted heart rate responses to CPX. PASC seems to impact exertional tolerance and exercise capacity due to ventilatory inefficiency, impaired aerobic metabolism, and potential systolic and autonomic dysfunction, all of these irrespective of support therapy during ICU stay.}, } @article {pmid38334067, year = {2024}, author = {Aggarwal, A and Singh, TK and Pham, M and Godwin, M and Chen, R and McIntyre, TM and Scalise, A and Chung, MK and Jennings, C and Ali, M and Park, H and Englund, K and Khorana, AA and Svensson, LG and Kapadia, S and McCrae, KR and Cameron, SJ}, title = {Dysregulated platelet function in patients with postacute sequelae of COVID-19.}, journal = {Vascular medicine (London, England)}, volume = {29}, number = {2}, pages = {125-134}, pmid = {38334067}, issn = {1477-0377}, support = {K08 HL128856/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; R01 HL158669/HL/NHLBI NIH HHS/United States ; R01 HL158801/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Factor Xa ; Blood Coagulation ; Disease Progression ; *Thrombosis/etiology ; }, abstract = {BACKGROUND: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC.

METHODS: patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions.

RESULTS: A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals.

CONCLUSIONS: patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.}, } @article {pmid38333536, year = {2024}, author = {Minotti, C and McKenzie, C and Dewandel, I and Bekker, C and Sturniolo, G and Doni, D and Giaquinto, C and Van Der Zalm, MM and Donà, D}, title = {How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review.}, journal = {EClinicalMedicine}, volume = {68}, number = {}, pages = {102436}, pmid = {38333536}, issn = {2589-5370}, support = {K43 TW011028/TW/FIC NIH HHS/United States ; }, abstract = {BACKGROUND: Post Coronavirus disease (COVID) and other post-viral infection syndromes present an overlap of pathogenesis, onset, progression, and symptom profile. We aimed to systematically describe studies on post-viral conditions and determine the entity of post COVID compared to other post-viral conditions in children.

METHODS: We conducted a systematic search of the Embase, MEDLINE, Cochrane Library, and GoogleScholar databases (January 1946-3 November 2023), according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The main outcomes were differences in condition duration, symptom type, and development of chronic symptoms. This systematic review was registered on PROSPERO (CRD42023401789).

FINDINGS: 35/5051 studies were included, with 42,934 children, adolescents and young adults (0-20 years old) overall. Twenty-eight studies focused on post COVID symptoms, followed by five papers on Respiratory Syncytial Virus (RSV) and Rhinovirus, one study on Epstein-Barr Virus (EBV), and one on gastrointestinal viruses. Studies on post COVID mainly reported data on older children/adolescents, describing long-lasting symptoms, including fatigue, neurologic, cardiorespiratory, musculoskeletal, mental health, and gastrointestinal symptoms. The maximum described symptoms duration was eighteen months, with an average follow-up of seven months. The development of chronic symptoms was reported by 30 studies (93.8%) for 10,473/28,474 patients (36.8%). Recovery was achieved in 18,001/28,474 cases (63.2%). The study on EBV reported persistent fatigue in adolescents for a similar duration (6 months, 46% chronic). Studies on RSV and Rhinovirus were mainly done in children under three years, with development of recurrent wheezing (up to 3 years).

INTERPRETATION: Post-viral fatigue was a shared feature between post COVID and post EBV conditions. A better understanding of post COVID as a unique condition, sharing features with other post-viral syndromes, is needed. The healthcare burden and socio-economic consequences for children and their families warrant further investigation and development of appropriate healthcare management plans. The foremost requirement is the establishment of consistent and shareable definitions, as well as a consensus on outcomes, to effectively evaluate follow-up and quantify the burden of different viral infections.

FUNDING: EU Horizon, EDCTP, NIH.}, } @article {pmid38333462, year = {2024}, author = {Haddad, A and Al-Maharmeh, Q and Kloub, MN and Ali, EA and Shaaban, H}, title = {Long-Lasting SARS-CoV-2 Infection With Post-COVID-19 Chronic Interstitial Pneumonia in a Patient With Chronic Lymphocytic Leukemia Treated Successfully With Intravenous Immunoglobulin.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51890}, pmid = {38333462}, issn = {2168-8184}, abstract = {Post-coronavirus disease 2019 (post-COVID-19) condition is a post-acute syndrome characterized by non-specific symptoms that remain for at least two months and typically appear three months after the start of the acute phase. Individuals with chronic lymphocytic leukemia (CLL) are considered to be at high risk of contracting COVID-19. It is also becoming increasingly evident that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is frequently lacking or insufficient. We present a 77-year-old male patient with CLL who had multiple hospitalizations for the management of pneumonia related to persistent COVID-19 infection due to hypogammaglobulinemia. He was subsequently treated with intravenous immunoglobulin (IVIG). This case emphasizes the importance of the early detection of hypogammaglobulinemia in patients with CLL and long COVID because of the potential therapeutic benefit of IVIG therapy. We also provide a literature review on COVID-19 infection in CLL patients, focusing mainly on the subset population of patients with hypergammaglobulinemia.}, } @article {pmid38333218, year = {2024}, author = {Furuya, C and Yasuda, H and Hiki, M and Shirane, S and Yamana, T and Uchimura, A and Inano, T and Takaku, T and Hamano, Y and Ando, M}, title = {Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1287300}, pmid = {38333218}, issn = {1664-3224}, mesh = {Male ; Humans ; Adult ; *COVID-19/complications ; SARS-CoV-2 ; *Hematologic Neoplasms ; *Lymphoma, Large B-Cell, Diffuse ; *Indazoles ; *Triazines ; *Triazoles ; }, abstract = {Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19.}, } @article {pmid38331459, year = {2024}, author = {Eddy, RL and Mummy, D and Zhang, S and Dai, H and Bechtel, A and Schmidt, A and Frizzell, B and Gerayeli, FV and Leipsic, JA and Leung, JM and Driehuys, B and Que, LG and Castro, M and Sin, DD and Niedbalski, PJ}, title = {Cluster analysis to identify long COVID phenotypes using [129]Xe magnetic resonance imaging: a multicentre evaluation.}, journal = {The European respiratory journal}, volume = {63}, number = {3}, pages = {}, pmid = {38331459}, issn = {1399-3003}, support = {R01 HL126771/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; Male ; Female ; Middle Aged ; *Magnetic Resonance Imaging/methods ; Cluster Analysis ; *Phenotype ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged ; Xenon Isotopes ; Lung/diagnostic imaging/physiopathology ; Case-Control Studies ; Pulmonary Gas Exchange ; }, abstract = {BACKGROUND: Long COVID impacts ∼10% of people diagnosed with coronavirus disease 2019 (COVID-19), yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that [129]Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID. Therefore, we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes.

METHODS: COVID-negative controls and participants who previously tested positive for COVID-19 underwent [129]Xe MRI ∼14 months post-acute infection across three centres. Long COVID was defined as persistent dyspnoea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully recovered. [129]Xe MRI ventilation defect percent (VDP) and membrane-to-gas (Mem/Gas), red blood cell-to-membrane (RBC/Mem) and red blood cell-to-gas (RBC/Gas) ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction.

RESULTS: We evaluated 135 participants across three centres: 28 COVID-negative (mean±sd age 40±16 years), 34 fully recovered (42±14 years) and 73 long COVID (49±13 years). RBC/Mem (p=0.03) and forced expiratory volume in 1 s (FEV1) (p=0.04) were different between long COVID and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster 1 was the youngest with normal MRI and mild gas trapping; Cluster 2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster 3 had mildly increased Mem/Gas with normal PFTs; and Cluster 4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern.

CONCLUSIONS: We identified four [129]Xe MRI long COVID phenotypes with distinct characteristics. [129]Xe MRI can dissect pathophysiological heterogeneity of long COVID to enable personalised patient care.}, } @article {pmid38331437, year = {2024}, author = {Iacobucci, G}, title = {Long covid: Online rehabilitation can improve quality of life, study reports.}, journal = {BMJ (Clinical research ed.)}, volume = {384}, number = {}, pages = {q346}, doi = {10.1136/bmj.q346}, pmid = {38331437}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19 ; }, } @article {pmid38331138, year = {2024}, author = {Bonner-Jackson, A and Vangal, R and Li, Y and Thompson, N and Chakrabarti, S and Krishnan, K}, title = {Factors Associated with Cognitive Impairment in Patients with Persisting Sequelae of COVID-19.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.01.021}, pmid = {38331138}, issn = {1555-7162}, abstract = {OBJECTIVE: Quantify cognitive deficits in patients with postacute sequelae of COVID-19 (PASC) and identify key variables related to cognitive impairment in PASC.

METHOD: Patients with polymerase chain reaction-confirmed COVID-19 underwent a comprehensive neuropsychological evaluation. The comparison group included patients without neurological disorders determined by the neuropsychologist to be cognitively intact. Cognitive impairment was defined as impairment (Composite T ≤35) in 1 of 6 cognitive domains. The PASC group was split into impaired or intact based on the above criteria. Multivariable logistic regression models assessed predictors including demographics, COVID-19 severity, clinical characteristics, and mood.

RESULTS: There were 210 patients with PASC, predominantly female (73.3%, P < .001), without other demographic differences when compared with 369 normal controls. Patients with PASC were more likely to have cognitive impairment (odds ratio 3.61; 95% confidence interval, 2.36-5.54; P < .001) compared with controls, with significantly lower scores in domains of memory, language, processing speed, visuospatial function, executive function (P < .001), and higher depressive (P = .004) and anxiety symptoms (P = .003). Patients with PASC who demonstrated cognitive impairment (n = 93) had higher body mass index compared with those with PASC without cognitive impairment (n = 117), without differences in other predictors.

CONCLUSION: Patients with PASC are almost 4 times more likely to evidence cognitive dysfunction compared with normal controls. Forty-four percent of patients with PASC demonstrated cognitive deficits about 7 months from infection. Estimated premorbid intelligence significantly correlated with impairment. Higher body mass index was the only metric shown to differentiate those with PASC and cognitive impairment from those with PASC who were cognitively intact.}, } @article {pmid38331137, year = {2024}, author = {Lee, JS and Choi, Y and Joung, JY and Son, CG}, title = {Clinical and Laboratory Characteristics of Fatigue-Dominant Long-COVID Subjects: A Cross-Sectional Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.01.025}, pmid = {38331137}, issn = {1555-7162}, abstract = {BACKGROUND: Long COVID is defined by persistent symptoms following COVID-19 infection. Approximately 71% of individuals with long COVID experience ongoing fatigue, postexertional malaise, and cognitive impairments, which share pathological similarities with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This similarity has prompted studies to explore the characteristics of long COVID to gain a better understanding of ME/CFS. To gain insights, we investigated the clinical and laboratory characteristics of individuals with fatigue-dominant long COVID.

METHODS: We enrolled 100 subjects (36 males, 64 females) with long COVID who had a higher score than 60 in the modified Korean version of the Chalder Fatigue Scale (mKCFQ11) and higher than 5 in a fatigue-focused visual analogue scale. To investigate fatigue symptoms, the mKCFQ11, the Multidimensional Fatigue Inventory, a visual analogue scale for fatigue and brain fog, along with the Short-Form survey, were employed. We also measured 3 cytokines and cortisol levels for immunological and endocrinological indicators. As a cross-sectional observational study, the data were collected at a single point in time.

RESULTS: The mean scores on the measurements showed severe fatigue, and these scores were significantly correlated, with no differences based on sex, the post-COVID period, or age. Among the laboratory tests, plasma cortisol levels had a significant negative correlation with fatigue scores and a positive correlation with living quality. The negative correlation between cortisol levels and mKCFQ11 scores appeared to be more specific to mental fatigue than physical, which conflicted with other measurements.

CONCLUSION: Our findings provide the first insights into the characteristics of fatigue in individuals with long COVID, particularly in terms of fatigue severity and cortisol levels. These results serve as valuable reference data for clinicians dealing with fatigue symptoms in long-COVID patients and for researchers exploring postviral fatigue symptoms, including ME/CFS, in the future.}, } @article {pmid38330962, year = {2024}, author = {Backes, C and Pecks, U and Keil, CN and Zöllkau, J and Scholz, C and Hütten, M and Rüdiger, M and Büchel, J and Andresen, K and Mand, N}, title = {Post-COVID in women after SARS-CoV-2 infection during pregnancy - a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS).}, journal = {Zeitschrift fur Geburtshilfe und Neonatologie}, volume = {228}, number = {1}, pages = {74-79}, doi = {10.1055/a-2213-1665}, pmid = {38330962}, issn = {1439-1651}, mesh = {Female ; Humans ; Infant, Newborn ; Pregnancy ; *COVID-19/epidemiology ; Follow-Up Studies ; Outcome Assessment, Health Care ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; *Pregnancy Complications, Infectious/diagnosis/epidemiology ; Pregnancy Outcome/epidemiology ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL).

METHODS: 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data.

RESULTS: 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL.

CONCLUSION: This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.}, } @article {pmid38330816, year = {2024}, author = {}, title = {Correspondence: Inaccurate reference leads to tripling of reported FND prevalence.}, journal = {NeuroImage. Clinical}, volume = {41}, number = {}, pages = {103537}, pmid = {38330816}, issn = {2213-1582}, mesh = {Humans ; Prevalence ; *Conversion Disorder ; }, abstract = {• Perez et al asserted that FND is the "2nd most common" diagnosis in outpatient neurology. • Stone et al (2010), cited by Perez et al, does not support the “2nd most common” claim. • In Stone et al, a broad “functional/psychological” category was the second most common. • FND is not synonymous with the “functional/psychological” category in Stone et al.}, } @article {pmid38330796, year = {2024}, author = {Fiorelli, D and Francavilla, B and Velletrani, G and Maurantonio, S and Passali, FM and Bernardini, S and Di Girolamo, S and Nuccetelli, M}, title = {Autoantibody profiles assessment in individuals with persistent olfactory impairment following SARS-CoV-2 infection.}, journal = {International immunopharmacology}, volume = {129}, number = {}, pages = {111599}, doi = {10.1016/j.intimp.2024.111599}, pmid = {38330796}, issn = {1878-1705}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anosmia ; Autoantibodies ; *Olfaction Disorders/etiology ; *Autoimmune Diseases ; }, abstract = {BACKGROUND: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection).

METHODS: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfactory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples.

RESULTS: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia.

CONCLUSION: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.}, } @article {pmid38330704, year = {2024}, author = {Navas-Otero, A and Calvache-Mateo, A and Calles-Plata, I and Valenza-Peña, G and Hernández-Hernández, S and Ortiz-Rubio, A and Valenza, MC}, title = {A lifestyle adjustments program in long COVID-19 improves symptomatic severity and quality of life. A randomized control trial.}, journal = {Patient education and counseling}, volume = {122}, number = {}, pages = {108180}, doi = {10.1016/j.pec.2024.108180}, pmid = {38330704}, issn = {1873-5134}, mesh = {Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Single-Blind Method ; *COVID-19 ; Life Style ; Chronic Disease ; }, abstract = {OBJECTIVE: To evaluate the efficacy of a therapeutic intervention based on self-adjustment strategies for improving of symptomatic severity and quality of life.

METHODS: The study was a randomised single-blind clinical trial. Quality of life, disability, and functional impairment were collected. The control group received a leaflet with information on the main symptoms of Long-COVID-19 syndrome, in addition to standard medical treatment. The intervention group received treatment following a dual approach; on the one hand, monitoring and recognition of symptomatology and on the other hand, adaptation and functional improvement.

RESULTS: A total of 54 participants were included, 27 were included in the intervention group and 27 in the control group. At the beginning of the study, no significant differences were found between groups. After intervention, the quality of life variable showed significant differences between groups in the self-care and anxiety/depression dimensions. Significant between-groups differences were also found for the self-care subscale of the disability variable. The intervention group showed significant differences from baseline on some subscales of the quality of life, disability, and functional impairment variables.

CONCLUSION: Strategies based on lifestyle adjustments are adequate for the improvement of quality of life and symptom severity in the long COVID-19 population.

PRACTICE IMPLICATION: The findings suggest that applying an intervention focused in self-adjustment for long COVID patients can have positive effects.}, } @article {pmid38328496, year = {2024}, author = {Maier, HE and Kowalski-Dobson, T and Eckard, A and Gherasim, C and Manthei, D and Meyers, A and Davis, D and Bakker, K and Lindsey, K and Chu, Z and Warsinske, L and Arnold, M and Buswinka, A and Stoneman, E and Valdez, R and Gordon, A}, title = {Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults.}, journal = {Open forum infectious diseases}, volume = {11}, number = {2}, pages = {ofae039}, pmid = {38328496}, issn = {2328-8957}, abstract = {BACKGROUND: The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting.

METHODS: The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020. Participants are actively followed for severe acute respiratory syndrome coronavirus 2 infection. We compared the prevalence of symptoms and symptom severity in vaccinated compared to unvaccinated cases. Our primary definition of long COVID was the presence of symptoms at 90 days postinfection; 30 days postinfection was also examined.

RESULTS: Overall, by 90 days postinfection, 13% of cases had long COVID, with 27% of unvaccinated cases and 8% of vaccinated cases reporting long COVID (relative risk [RR], 0.31 [95% confidence interval {CI}, .22-.42]). Vaccination was also associated with significantly lower average severity scores at all timepoints (eg, relative severity at 90 days postinfection: -2.70 [95% CI, -1.68 to -3.73]). In the pre-Omicron era, 28% of unvaccinated cases and 18% of vaccinated cases reported long COVID (P = .07), and vaccinated cases reported less severe symptoms including less difficulty breathing (P = .01; 90-day RR, 0.07).

CONCLUSIONS: Vaccinated cases had lower prevalence of long COVID and reduced symptom severity.}, } @article {pmid38327880, year = {2024}, author = {Gil, A and Hoag, GE and Salerno, JP and Hornig, M and Klimas, N and Selin, LK}, title = {Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series.}, journal = {Brain, behavior, & immunity - health}, volume = {36}, number = {}, pages = {100720}, pmid = {38327880}, issn = {2666-3546}, abstract = {BACKGROUND: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

METHODS: and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3-15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.

CONCLUSIONS: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.}, } @article {pmid38327277, year = {2024}, author = {Bello-Chavolla, OY and Fermín-Martínez, CA and Ramírez-García, D and Vargas-Vázquez, A and Fernández-Chirino, L and Basile-Alvarez, MR and Sánchez-Castro, P and Núñez-Luna, A and Antonio-Villa, NE}, title = {Prevalence and determinants of post-acute sequelae after SARS-CoV-2 infection (Long COVID) among adults in Mexico during 2022: a retrospective analysis of nationally representative data.}, journal = {Lancet regional health. Americas}, volume = {30}, number = {}, pages = {100688}, pmid = {38327277}, issn = {2667-193X}, abstract = {BACKGROUND: Post-acute sequelae after SARS-CoV-2 infection (PASC) remains a concerning long-term complication of COVID-19. Here, we aimed to characterize the epidemiology of PASC in Mexico during 2022 and identify potential associations of covariates with PASC prevalence using nationally representative data.

METHODS: We analyzed data from the 2022 Mexican National Health and Nutrition Survey (ENSANUT) from 24,434 participants, representing 85,521,661 adults ≥20 years. PASC was defined using both the National Institute for Health and Care Excellence (NICE) definition and a PASC score ≥12. Estimates of PASC prevalence were stratified by age, sex, rural vs. urban setting, social lag quartiles, number of reinfections, vaccination status and periods of predominance of SARS-CoV-2 circulating variants. Determinants of PASC were assessed using log-binomial regression models adjusted by survey weights.

FINDINGS: Persistent symptoms after SARS-CoV-2 infection were reported by 12.44% (95% CI 11.89-12.99) of adults ≥20 years in Mexico in 2022. The most common persistent symptoms were fatigue, musculoskeletal pain, headache, cough, loss of smell or taste, fever, post-exertional malaise, brain fog, anxiety, and chest pain. PASC was present in 21.21% (95% CI 19.74-22.68) of subjects with previously diagnosed COVID-19. Over 28.6% of patients with PASC reported symptoms persistence ≥6 months and 14.05% reported incapacitating symptoms. Higher PASC prevalence was associated with SARS-CoV-2 reinfections, depressive symptoms and living in states with high social lag. PASC prevalence, particularly its more severe forms, decreased with COVID-19 vaccination and for infections during periods of Omicron variant predominance.

INTERPRETATION: PASC remains a significant public health burden in Mexico as the COVID-19 pandemic transitions into endemic. Promoting SARS-CoV-2 reinfection prevention and booster vaccination may be useful in reducing PASC burden.

FUNDING: This research was supported by Instituto Nacional de Geriatría in Mexico.}, } @article {pmid38326247, year = {2024}, author = {Bidhendi-Yarandi, R and Biglarian, A and Bakhshi, E and Khodaei-Ardakani, MR and Behboudi-Gandevani, S}, title = {Prevalence of depression, stress and suicide tendency among individuals with long COVID and determinants: a protocol of a systematic review and meta-analysis.}, journal = {BMJ open}, volume = {14}, number = {2}, pages = {e075754}, pmid = {38326247}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Prevalence ; Pandemics ; Bayes Theorem ; Systematic Reviews as Topic ; Suicidal Ideation ; Meta-Analysis as Topic ; Review Literature as Topic ; }, abstract = {BACKGROUND: It is well known that the COVID-19 pandemic has had a devastating impact on mental health, especially among individuals with long COVID. This systematic review and meta-analysis aims to investigate the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as to explore the factors that contribute to these conditions.

METHODS AND ANALYSIS: A comprehensive review of literature will be conducted in various databases of including PubMed, including Medline, Embase, PsycINFO, CINAHL and Cochrane Library. The studies to be included in this review will be published in the English language, and the time frame of included studies will be from the date of inception of COVID-19 until 30 December 2023. Two independent reviewers will identify studies for inclusion based on a screening questionnaire, and the JBI standardised critical appraisal checklist for studies reporting prevalence data will be used to assess the methodological quality. The strength of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. To analyse the data, a robust Bayesian approach will be applied using the STATA software package (V.14; STATA) and JASP software. The findings of this systematic review and meta-analysis will provide valuable insights into the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as the factors that contribute to these conditions.

ETHICS AND DISSEMINATION: There is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal.

PROSPERO REGISTRATION NUMBER: CRD42022346858.}, } @article {pmid38326099, year = {2024}, author = {Donnelly, SC}, title = {The Long-COVID Syndrome-how to assess in real-time an individuals well-being-the COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm).}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {117}, number = {1}, pages = {1}, doi = {10.1093/qjmed/hcae011}, pmid = {38326099}, issn = {1460-2393}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38325873, year = {2024}, author = {McGregor, G and Sandhu, H and Bruce, J and Sheehan, B and McWilliams, D and Yeung, J and Jones, C and Lara, B and Alleyne, S and Smith, J and Lall, R and Ji, C and Ratna, M and Ennis, S and Heine, P and Patel, S and Abraham, C and Mason, J and Nwankwo, H and Nichols, V and Seers, K and Underwood, M}, title = {Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial.}, journal = {BMJ (Clinical research ed.)}, volume = {384}, number = {}, pages = {e076506}, pmid = {38325873}, issn = {1756-1833}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cost-Benefit Analysis ; *COVID-19 ; Pain ; Post-Acute COVID-19 Syndrome ; *Psychiatric Rehabilitation ; Quality of Life ; Treatment Outcome ; }, abstract = {OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid).

DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial.

SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub.

PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287).

INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions.

MAIN OUTCOME MEASURES: The primary outcome was health related quality of life using the patient reported outcomes measurement information system (PROMIS) preference (PROPr) score at three months. Secondary outcomes, measured at three, six, and 12 months, included PROMIS subscores (depression, fatigue, sleep disturbance, pain interference, physical function, social roles/activities, and cognitive function), severity of post-traumatic stress disorder, general health, and adverse events.

RESULTS: Between January 2021 and July 2022, 39 697 people were invited to take part in the study and 725 were contacted and eligible. 585 participants were randomised. Mean age was 56 (standard deviation (SD) 12) years, 52% were female participants, mean health related quality of life PROMIS-PROPr score was 0.20 (SD 0.17), and mean time from hospital discharge was 323 (SD 144) days. Compared with usual care, the REGAIN intervention led to improvements in health related quality of life (adjusted mean difference in PROPr score 0.03 (95% confidence interval 0.01 to 0.05), P=0.02) at three months, driven predominantly by greater improvements in the PROMIS subscores for depression (1.39 (0.06 to 2.71), P=0.04), fatigue (2.50 (1.19 to 3.81), P<0.001), and pain interference (1.80 (0.50 to 3.11), P=0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P=0.02). Of 21 serious adverse events, only one was possibly related to the REGAIN intervention. In the intervention group, 141 (47%) participants fully adhered to the programme, 117 (39%) partially adhered, and 40 (13%) did not receive the intervention.

CONCLUSIONS: In adults with post-covid-19 condition, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at three and 12 months compared with usual care.

TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448.}, } @article {pmid38324547, year = {2024}, author = {Asadi-Pooya, AA and Nemati, M and Shahisavandi, M and Nemati, H and Karimi, A and Jafari, A and Nasiri, S and Mohammadi, SS and Rahimian, Z and Bayat, H and Akbari, A and Emami, A and Eilami, O}, title = {How does COVID-19 vaccination affect long-COVID symptoms?.}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0296680}, pmid = {38324547}, issn = {1932-6203}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; *COVID-19/epidemiology/prevention & control ; Follow-Up Studies ; Retrospective Studies ; Vaccination ; }, abstract = {OBJECTIVE: The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition.

METHODS: This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate.

RESULTS: In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032).

CONCLUSIONS: In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.}, } @article {pmid38324145, year = {2024}, author = {Poyatos, P and Luque, N and Sabater, G and Eizaguirre, S and Bonnin, M and Orriols, R and Tura-Ceide, O}, title = {Endothelial dysfunction and cardiovascular risk in post-COVID-19 patients after 6- and 12-months SARS-CoV-2 infection.}, journal = {Infection}, volume = {52}, number = {4}, pages = {1269-1285}, pmid = {38324145}, issn = {1439-0973}, support = {IFUdG2021//Universitat de Girona/ ; CP17/00114//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *COVID-19/complications/physiopathology/blood ; Male ; Female ; Middle Aged ; *Cardiovascular Diseases/epidemiology/etiology ; *SARS-CoV-2 ; Endothelium, Vascular/physiopathology ; Aged ; Adult ; Biomarkers/blood ; Endothelial Progenitor Cells ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: SARS-CoV-2 infection causes severe endothelial damage, an essential step for cardiovascular complications. Endothelial-colony forming cells (ECFCs) act as a biomarker of vascular damage but their role in SARS-CoV-2 remain unclear. The aim of this study was to assess whether the number of ECFCs and angiogenic biomarkers remained altered after 6 and 12-months post-infection and whether this imbalance correlated with the presence of long-COVID syndrome and other biological parameters measured.

METHODS: Seventy-two patients were recruited at different time-points after overcoming COVID-19 and thirty-one healthy controls. All subjects were matched for age, gender, BMI, and comorbidities. ECFCs were obtained from peripheral blood and cultured with specific conditions.

RESULTS: The results confirm the presence of a long-term sequela in post-COVID-19 patients, with an abnormal increase in ECFC production compared to controls (82.8% vs. 48.4%, P < 0.01) that is maintained up to 6-months (87.0% vs. 48.4%, P < 0.01) and 12-months post-infection (85.0% vs. 48.4%, P < 0.01). Interestingly, post-COVID-19 patients showed a significant downregulation of angiogenesis-related proteins compared to controls indicating a clear endothelial injury. Troponin, NT-proBNP and ferritin levels, markers of cardiovascular risk and inflammation, remained elevated up to 12-months post-infection. Patients with lower numbers of ECFC exhibited higher levels of inflammatory markers, such as ferritin, suggesting that ECFCs may play a protective role. Additionally, long-COVID syndrome was associated with higher ferritin levels and with female gender.

CONCLUSIONS: These findings highlight the presence of vascular sequela that last up to 6- and 12-months post-infection and point out the need for preventive measures and patient follow-up.}, } @article {pmid38321938, year = {2024}, author = {Rao, S and Gross, RS and Mohandas, S and Stein, CR and Case, A and Dreyer, B and Pajor, NM and Bunnell, HT and Warburton, D and Berg, E and Overdevest, JB and Gorelik, M and Milner, J and Saxena, S and Jhaveri, R and Wood, JC and Rhee, KE and Letts, R and Maughan, C and Guthe, N and Castro-Baucom, L and Stockwell, MS}, title = {Postacute Sequelae of SARS-CoV-2 in Children.}, journal = {Pediatrics}, volume = {153}, number = {3}, pages = {}, pmid = {38321938}, issn = {1098-4275}, support = {K23 DC019678/DC/NIDCD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 DK111022/DK/NIDDK NIH HHS/United States ; }, mesh = {Child ; Humans ; *Autoimmune Diseases ; *COVID-19/complications/epidemiology ; Disease Progression ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome ; United States ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.}, } @article {pmid38321404, year = {2024}, author = {Seighali, N and Abdollahi, A and Shafiee, A and Amini, MJ and Teymouri Athar, MM and Safari, O and Faghfouri, P and Eskandari, A and Rostaii, O and Salehi, AH and Soltani, H and Hosseini, M and Abhari, FS and Maghsoudi, MR and Jahanbakhshi, B and Bakhtiyari, M}, title = {The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis.}, journal = {BMC psychiatry}, volume = {24}, number = {1}, pages = {105}, pmid = {38321404}, issn = {1471-244X}, mesh = {Humans ; *Anxiety/epidemiology ; Coping Skills ; *Depression/epidemiology ; *Post-Acute COVID-19 Syndrome/psychology ; Prevalence ; *Sleep Wake Disorders/epidemiology ; }, abstract = {BACKGROUND: Post COVID-19 syndrome, also known as "Long COVID," is a complex and multifaceted condition that affects individuals who have recovered from SARS-CoV-2 infection. This systematic review and meta-analysis aim to comprehensively assess the global prevalence of depression, anxiety, and sleep disorder in individuals coping with Post COVID-19 syndrome.

METHODS: A rigorous search of electronic databases was conducted to identify original studies until 24 January 2023. The inclusion criteria comprised studies employing previously validated assessment tools for depression, anxiety, and sleep disorders, reporting prevalence rates, and encompassing patients of all age groups and geographical regions for subgroup analysis Random effects model was utilized for the meta-analysis. Meta-regression analysis was done.

RESULTS: The pooled prevalence of depression and anxiety among patients coping with Post COVID-19 syndrome was estimated to be 23% (95% CI: 20%-26%; I2 = 99.9%) based on data from 143 studies with 7,782,124 participants and 132 studies with 9,320,687 participants, respectively. The pooled prevalence of sleep disorder among these patients, derived from 27 studies with 15,362 participants, was estimated to be 45% (95% CI: 37%-53%; I2 = 98.7%). Subgroup analyses based on geographical regions and assessment scales revealed significant variations in prevalence rates. Meta-regression analysis showed significant correlations between the prevalence and total sample size of studies, the age of participants, and the percentage of male participants. Publication bias was assessed using Doi plot visualization and the Peters test, revealing a potential source of publication bias for depression (p = 0.0085) and sleep disorder (p = 0.02). However, no evidence of publication bias was found for anxiety (p = 0.11).

CONCLUSION: This systematic review and meta-analysis demonstrate a considerable burden of mental health issues, including depression, anxiety, and sleep disorders, among individuals recovering from COVID-19. The findings emphasize the need for comprehensive mental health support and tailored interventions for patients experiencing persistent symptoms after COVID-19 recovery.}, } @article {pmid39017131, year = {2023}, author = {Sutherland, S}, title = {The Brain and Long COVID: Millions of people are still suffering long after infection. Now researchers are finding neurological causes for their symptoms.}, journal = {Scientific American}, volume = {328}, number = {3}, pages = {26}, doi = {10.1038/scientificamerican0323-26}, pmid = {39017131}, issn = {0036-8733}, } @article {pmid39017114, year = {2023}, author = {Helmuth, L}, title = {Quark Soup: Long COVID is a neurological disease, we can learn about pregnancy from other species, and the universe may be a hologram: highlights from the March issue of Scientific American.}, journal = {Scientific American}, volume = {328}, number = {3}, pages = {4}, doi = {10.1038/scientificamerican0323-4}, pmid = {39017114}, issn = {0036-8733}, } @article {pmid38406213, year = {2023}, author = {Rubinstein, RJ and Mei, W and Cassidy, CA and Streeter, G and Basham, C and Cerami, C and Lin, FC and Lin, JT and Mollan, KR}, title = {Transmission prevention behaviors in US households with SARS-CoV-2 cases in 2020.}, journal = {Frontiers in epidemiology}, volume = {3}, number = {}, pages = {}, pmid = {38406213}, issn = {2674-1199}, support = {P30 AI050410/AI/NIAID NIH HHS/United States ; T32 DK007634/DK/NIDDK NIH HHS/United States ; T32 GM008719/GM/NIGMS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors.

METHODS: We analyzed a COVID-19 prospective household transmission cohort in North Carolina (April to October 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between days 7-14.

RESULTS: In the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between days 7-14 was reported by 26% of household contacts and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case.

DISCUSSION: In-home masking during household exposure to COVID-19 was infrequent in 2020. In light of the ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors.}, } @article {pmid38322108, year = {2023}, author = {Boyarchuk, O and Volianska, L}, title = {Autoimmunity and long COVID in children.}, journal = {Reumatologia}, volume = {61}, number = {6}, pages = {492-501}, pmid = {38322108}, issn = {0034-6233}, abstract = {Numerous hypotheses regarding the pathogenetic mechanisms of long COVID have been proposed. Immune dysregulation and autoimmunity are among the leading hypotheses. In this article, we present two clinical cases of long COVID. The first case demonstrates the phenotype of long COVID with pain and musculoskeletal symptoms, which is often associated with autoimmunity and mimics systemic connective tissue diseases. In the second case, a high titer of antinuclear antibodies was observed after SARS-CoV-2 infection, but the clinical symptoms were limited to fever and headache. Only a comprehensive evaluation of clinical symptoms and thorough objective examination can confirm or exclude autoimmune diseases after a previous SARS-CoV-2 infection. A systematic search in the PubMed Medline database was carried out for studies focusing on immune dysregulation, autoimmunity, and its association with the clinical phenotype of long COVID. The question of the role of autoimmunity in the development of long COVID and the management approaches are discussed.}, } @article {pmid38449902, year = {2022}, author = {Mutiawati, E and Kusuma, HI and Fathima, R and Syahrul, S and Musadir, N}, title = {A comparison study of headache characteristics and headache-associated quality-of-life of COVID-19 and non-COVID-19 patients.}, journal = {Narra J}, volume = {2}, number = {3}, pages = {e93}, pmid = {38449902}, issn = {2807-2618}, abstract = {Headache is prevalent in coronavirus disease 2019 (COVID-19) patients. The main objective of this study was to compare the characteristics of COVID-19-associated headache to non-COVID-19 headache. The quality-of-life (QoL) and its associated determinants between COVID-19 and non-COVID-19 patients were also compared. A cross-sectional study was conducted in Banda Aceh, Indonesia. Headache and QoL were assessed using the International Classification of Headache Disorders, version 3 (ICHD-3), and the 36-item Short Form Health Survey (SF-36), respectively. Factors associated with poor QoL in COVID-19 and non-COVID-19 patients were examined using logistic regression. A total of 356 headache patients were included: 215 COVID-19 and 141 non-COVID-19 patients. Our data suggested that the headache in COVID-19 patients was bilateral; pain centered on one specific area with a pulsating or pressing sensation; pain intensity ranging from moderate to severe; and the frequency ranging from more than twice per week to every day. Non-COVID-19 headache was bilateral; pain centered on one side of the head resembling a migraine with pulsating or pressing sensation; mild to moderate pain intensity; and the frequency of one or two times per month. In COVID-19, low QoL was associated with unemployment status, having non-health-related jobs, having used painkillers to reduce the pain, having long duration of headache, having more frequency of attacks, and having headaches that were worsened by activities or light, and having additional symptom during a headache attach. In non-COVID-19 patients, poor QoL was associated with the use of painkillers, long duration of headache, and having conditions that aggravate the headache. To prevent long-term effects of headache associated with COVID-19, studies exploring the photobiology of headache are needed, along with the necessity of having standardised guideline on headache prevention.}, } @article {pmid38827572, year = {2021}, author = {Montes de Oca-B, P}, title = {Evidence of mitochondria origin of SARS-CoV-2 double-membrane vesicles: a review.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {1009}, pmid = {38827572}, issn = {2046-1402}, mesh = {Humans ; *Mitochondria/metabolism ; *SARS-CoV-2/physiology ; *COVID-19/virology ; Virus Replication ; }, abstract = {Coronavirus Disease-19 (COVID-19) pandemic is caused by SARS-CoV-2 that has infected more than 600 million people and killed more than 6 million people worldwide. This infection affects mainly certain groups of people that have high susceptibility to present severe COVID-19 due to comorbidities. Moreover, the long-COVID-19 comprises a series of symptoms that may remain in some patients for months after infection that further compromises their health. Thus, since this pandemic is profoundly affecting health, economy, and social life of societies, a deeper understanding of viral replication cycle could help to envisage novel therapeutic alternatives that limit or stop COVID-19. Several findings have unexpectedly discovered that mitochondria play a critical role in SARS-CoV-2 cell infection. Indeed, it has been suggested that this organelle could be the origin of its replication niches, the double membrane vesicles (DMV). In this regard, mitochondria derived vesicles (MDV), involved in mitochondria quality control, discovered almost 15 years ago, comprise a subpopulation characterized by a double membrane. MDV shedding is induced by mitochondrial stress, and it has a fast assembly dynamic, reason that perhaps has precluded their identification in electron microscopy or tomography studies. These and other features of MDV together with recent SARS-CoV-2 protein interactome and other findings link SARS-CoV-2 to mitochondria and support that these vesicles are the precursors of SARS-CoV-2 induced DMV. In this work, the morphological, biochemical, molecular, and cellular evidence that supports this hypothesis is reviewed and integrated into the current model of SARS-CoV-2 cell infection. In this scheme, some relevant questions are raised as pending topics for research that would help in the near future to test this hypothesis. The intention of this work is to provide a novel framework that could open new possibilities to tackle SARS-CoV-2 pandemic through mitochondria and DMV targeted therapies.}, } @article {pmid38389548, year = {2022}, author = {Rodríguez Cárdenas, YA}, title = {[Long COVID and oral health: are we ready?].}, journal = {Revista cientifica odontologica (Universidad Cientifica del Sur)}, volume = {10}, number = {3}, pages = {e114}, pmid = {38389548}, issn = {2523-2754}, } @article {pmid38515879, year = {2022}, author = {Eichler, S and Carnarius, S and Steiger, E and von Stillfried, D}, title = {Interrupting chains of respiratory infections via remote patient monitoring in ambulatory care - a randomized controlled trial during the 2020/21 infection season.}, journal = {Dialogues in health}, volume = {1}, number = {}, pages = {100021}, pmid = {38515879}, issn = {2772-6533}, abstract = {AIM OF THE STUDY: The aim of the study was to investigate patient satisfaction, saving of time and the possible reduction of visits to medical practices that use Remote Patient Monitoring (RPM) during treatment compared to usual care.

METHODS: In a randomized controlled trial between October 2020 and May 2021, the participating medical practices were randomized into three groups (two different RPM systems, one control). Doctors were required to enroll patients ≥18 years with acute respiratory infection in possession of a web-enabled device, such as a laptop, tablet or computer. After a three-month study phase, doctors were asked to describe the treatment of their patients via online survey. Patients were also questioned. The analysis was carried out descriptively and through group comparisons.

RESULTS: 51 practices with 121 patients were included. Overall, the results generally show a positive assessment of digital care on the patient side. As for the doctors, handling and integrating the systems into established practice routines seem to be a challenge. Further, the number of patient visits to the medical practice was not reduced by using the systems. Doctors did not save time, but the relationship to the patients was intensified.

CONCLUSION: While there was no indication for an increase in efficiency by using RPM systems, participating doctors indicated their potential for an enhanced interaction between doctor and patient. In particular, intensified interaction contact with patients with chronic diseases (e. g. COPD, long-COVID) could be of long-term interest and importance for doctors in ambulatory care.Trial Registration: DRKS00023553.}, } @article {pmid39016768, year = {2022}, author = {O'Rourke, M}, title = {Long Haulers Called Attention to Chronic Illnesses: But society is not prepared for the growing crisis of long COVID.}, journal = {Scientific American}, volume = {326}, number = {3}, pages = {56}, doi = {10.1038/scientificamerican0322-56}, pmid = {39016768}, issn = {0036-8733}, } @article {pmid38560070, year = {2022}, author = {Sathyamoorthy, M and Verduzco-Gutierrez, M and Varanasi, S and Ward, R and Spertus, J and Shah, S}, title = {Enhanced external counterpulsation for management of symptoms associated with long COVID.}, journal = {American heart journal plus : cardiology research and practice}, volume = {13}, number = {}, pages = {100105}, pmid = {38560070}, issn = {2666-6022}, abstract = {STUDY OBJECTIVE: Enhanced external counterpulsation (EECP) as a possible therapy for Long COVID.

DESIGN: Retrospective analysis of a contemporary, consecutive patient cohort.

SETTING: 7 outpatient treatment centers.

PARTICIPANTS: Long COVID patients.

INTERVENTION: 15-35 EECP treatments.

MAIN OUTCOME MEASURES: The change from baseline in 1) Patient Reported Outcome Measurement Information System (PROMIS) Fatigue; 2) Seattle Angina Questionnaire (SAQ); 3) Duke Activity Status Index (DASI); 4) 6-Minute Walk Test (6MWT); 5) Canadian Cardiovascular Society (CCS) Angina Grade; 6) Rose Dyspnea Scale (RDS); and 7) Patient Health Questionnaire (PHQ-9).

RESULTS: Compared to baseline, the PROMIS Fatigue, SAQ, DASI, and 6MWT improved by 4.63 ± 3.42 (p < 0.001), 21.44 ± 16.54 (p < 0.001), 18.08 ± 13.82 (p < 0.001), and 200.00 ± 180.14 (p = 0.002), respectively. CCS and RDS improved in 63% and 44% of patients, respectively. All patients unable to work prior to EECP were able to return post-therapy.

CONCLUSIONS AND RELEVANCE: EECP significantly improved validated fatigue and cardiovascular-related markers in patients with Long COVID.}, } @article {pmid38620971, year = {2021}, author = {Membrilla, JA and Caronna, E and Trigo-López, J and González-Martínez, A and Layos-Romero, A and Pozo-Rosich, P and Guerrero-Peral, Á and Gago-Veiga, AB and Andrés-López, A and Díaz de Terán, J}, title = {Persistent headache after COVID-19: Pathophysioloy, clinic and treatment.}, journal = {Neurology perspectives}, volume = {1}, number = {}, pages = {S31-S36}, pmid = {38620971}, issn = {2667-0496}, abstract = {SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors' clinical experience.}, } @article {pmid38449463, year = {2021}, author = {Fahriani, M and Ilmawan, M and Fajar, JK and Maliga, HA and Frediansyah, A and Masyeni, S and Yusuf, H and Nainu, F and Rosiello, F and Sirinam, S and Keam, S and Ophinni, Y}, title = {Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis - A systematic review and meta-analysis.}, journal = {Narra J}, volume = {1}, number = {2}, pages = {e36}, pmid = {38449463}, issn = {2807-2618}, abstract = {The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed. PROSPERO registration: CRD42021247172.}, } @article {pmid38321333, year = {2024}, author = {Badulescu, S and Le, GH and Wong, S and Kwan, ATH and Guo, Z and Teopiz, KM and Phan, L and Subramaniapillai, M and Rosenblat, JD and Mansur, RB and McIntyre, RS}, title = {Impact of vortioxetine on psychosocial functioning moderated by symptoms of fatigue in post-COVID-19 condition: a secondary analysis.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {4}, pages = {1335-1342}, pmid = {38321333}, issn = {1590-3478}, mesh = {Humans ; Vortioxetine/therapeutic use ; Post-Acute COVID-19 Syndrome ; Psychosocial Functioning ; *Depressive Disorder, Major/diagnosis ; *COVID-19/complications ; Fatigue/drug therapy/etiology ; }, abstract = {INTRODUCTION: Fatigue is a prominent symptom in post-COVID condition (PCC) sequelae, termed "long COVID." Herein, we aim to ascertain the effect of fatigue on psychosocial function in persons living with PCC.

METHODS: This post hoc analysis evaluated the effects of vortioxetine on measures of fatigue as assessed by the Fatigue Severity Scale (FSS) in psychosocial function as measured by the Sheehan Disability Scale (SDS) in persons with PCC. We also evaluated the change in FSS on psychosocial functioning as measured by the Sheehan Disability Scale (SDS). This post hoc analysis obtained data from a recently published placebo-controlled study evaluating vortioxetine's effect on objective cognitive functions in persons living with PCC.

RESULTS: One hundred forty-four participants meeting World Health Organization (WHO) criteria for PCC were included in this analysis. At the end of 8 weeks of vortioxetine treatment, significant improvement of all domains was observed for psychosocial functioning. There was a significant between-group difference at treatment endpoint in the family, social, and work SDS subcategories (p < 0.001). There was a statistically significant interaction effect between the treatment condition time point and FSS effect on the SDS social (χ[2] = 10.640, p = 0.014) and work (χ[2] = 9.342, p = 0.025) categories but a statistically insignificant effect on the family categories ((χ[2] = 5.201, p = 0.158)).

DISCUSSION: This post hoc analysis suggests that vortioxetine treatment significantly improves psychosocial function in persons with PCC. Our results also indicate that the improvement in psychosocial function was significantly mediated by improvement in measures of fatigue. Our results provide empirical support for recommendations to identify therapeutics for fatigue in persons living with PCC with a broader aim to improve psychosocial function in this common and severely impaired population.}, } @article {pmid38320835, year = {2024}, author = {Borgonovo, F and Lovaglio, PG and Mariani, C and Berta, P and Cossu, MV and Rizzardini, G and Vittadini, G and Capetti, AF}, title = {Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study.}, journal = {BMJ open}, volume = {14}, number = {2}, pages = {e075185}, pmid = {38320835}, issn = {2044-6055}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Prospective Studies ; Quality of Life ; Cohort Studies ; }, abstract = {OBJECTIVE: To define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome.

DESIGN: A single-centre longitudinal prospective cohort study conducted from May 2020 to October 2022.

SETTING: The study was conducted at Luigi Sacco University Hospital in Milan (Italy). In May 2020, we activated the ARCOVID (Ambulatorio Rivalutazione COVID) outpatient service for the follow-up of long COVID.

PARTICIPANTS: Hospitalised and non-hospitalised patients previously affected by COVID-19 were either referred by specialists or general practitioners or self-referred.

INTERVENTION: During the first visit, a set of questions investigated the presence and the duration of 11 symptoms (palpitations, amnesia, headache, anxiety/panic, insomnia, loss of smell, loss of taste, dyspnoea, asthenia, myalgia and telogen effluvium). The follow-up has continued until the present time, by sending email questionnaires every 3 months to monitor symptoms and health-related quality of life.

Measurement of synthetic scores (aggregation of symptoms based on occurrence and duration) that may reveal the presence of long COVID in different clinical macro symptoms. To this end, a mixed supervised and empirical strategy was adopted. Moreover, we aimed to identify predictive factors for post-COVID-19 macro symptoms.

RESULTS: In the first and second waves of COVID-19, 575 and 793 patients (respectively) were enrolled. Three different post-COVID-19 macro symptoms (neurological, sensorial and physical) were identified. We found significant associations between post-COVID-19 symptoms and (1) the patients' comorbidities, and (2) the medications used during the COVID-19 acute phase. ACE inhibitors (OR=2.039, 95% CI: 1.095 to 3.892), inhaled steroids (OR=4.08, 95% CI: 1.17 to 19.19) and COVID therapies were associated with increased incidence of the neurological macro symptoms. Age (OR=1.02, 95% CI: 1.01 to 1.04), COVID-19 severity (OR=0.42, 95% CI: 0.21 to 0.82), number of comorbidities (OR=1.22, 95% CI: 1.01 to 1.5), metabolic (OR=2.52, 95% CI: 1.25 to 5.27), pulmonary (OR=1.87, 95% CI: 1.10 to 3.32) and autoimmune diseases (OR=4.57, 95% CI: 1.57 to 19.41) increased the risk of the physical macro symptoms.

CONCLUSIONS: Being male was the unique protective factor in both waves. Other factors reflected different medical behaviours and the impact of comorbidities. Evidence of the effect of therapies adds valuable information that may drive future medical choices.}, } @article {pmid38320192, year = {2023}, author = {Lineburg, KE and Smith, C}, title = {The Persistence of SARS-CoV-2 and Its Role in Long Covid.}, journal = {NEJM evidence}, volume = {2}, number = {9}, pages = {EVIDe2300165}, doi = {10.1056/EVIDe2300165}, pmid = {38320192}, issn = {2766-5526}, mesh = {Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cytokines ; Disease Progression ; }, abstract = {Postacute sequelae of coronavirus disease 2019 (PASC), more commonly known as long Covid, manifests as ongoing symptoms in various organs of the body more than 4 weeks after the resolution of acute Covid-19.[1] A prevalent symptom of PASC is an ongoing loss of taste, but additional persisting symptoms can include neurologic, gastrointestinal, kidney, lung, or heart dysfunction.[1,2] There are two broad mechanisms that are thought to underpin the ongoing complications associated with PASC: dysregulated production of inflammatory cytokines and the persistence of virus.[3].}, } @article {pmid38319491, year = {2024}, author = {Lubell, J}, title = {People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing.}, journal = {Angiogenesis}, volume = {27}, number = {2}, pages = {123-124}, pmid = {38319491}, issn = {1573-7209}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Wound Healing ; Endothelium ; Connective Tissue ; }, abstract = {A growing body of evidence documents the central role that endothelial damage plays in the pathophysiology of long COVID. But it remains unclear why only certain people get Long COVID and why recovery times are so long for many affected individuals. One potential explanation is that some forms of long COVID are experienced disproportionately by people with a connective tissue disorder who are more vulnerable than others to incurring serious damage to the endothelium and the vascular extracellular matrix from the inflammatory processes triggered by COVID-19 and much slower to heal. Further research is needed to explore this hypothesis.}, } @article {pmid38319477, year = {2024}, author = {Villa, A and Milito, C and Deiana, CM and Finco Gambier, R and Punziano, A and Buso, H and Bez, P and Lagnese, G and Garzi, G and Costanzo, G and Giannuzzi, G and Pagnozzi, C and Dalm, VASH and Spadaro, G and Rattazzi, M and Cinetto, F and Firinu, D}, title = {High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study.}, journal = {Journal of clinical immunology}, volume = {44}, number = {2}, pages = {59}, pmid = {38319477}, issn = {1573-2592}, mesh = {United States ; Humans ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Common Variable Immunodeficiency/epidemiology ; Prevalence ; SARS-CoV-2 ; Italy/epidemiology ; }, abstract = {The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections. The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection. In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC. In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.}, } @article {pmid38319396, year = {2024}, author = {Zhang, S and Yuan, M and He, D and Dang, W and Zhang, W}, title = {Long-term follow-up of brain regional changes and the association with cognitive impairment in quarantined COVID-19 survivors.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1911-1922}, pmid = {38319396}, issn = {1433-8491}, support = {2020YFS0582//Sichuan Province Science and Technology Support Program/ ; ZYJC21004//West China Hospital, Sichuan University/ ; 2020HXBH041//West China Hospital, Sichuan University/ ; }, mesh = {Humans ; *COVID-19/complications ; Male ; *Cognitive Dysfunction/etiology/physiopathology ; Female ; Middle Aged ; *Survivors ; *Magnetic Resonance Imaging ; Follow-Up Studies ; *Quarantine ; Adult ; *Brain/diagnostic imaging/pathology/physiopathology ; Aged ; Neuropsychological Tests ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: This study aimed to evaluate the neuropsychiatric symptoms of quarantined COVID-19 survivors 15 months after discharge and explore its potential association with structural and functional brain changes and inflammation.

METHODS: A total of 51 quarantined COVID-19 survivors and 74 healthy controls were included in this study. Cognitive function was assessed using the THINC-integrated tool. Structural brain changes were examined through both surface- and volume-based analyses, and functional changes were assessed using resting-state amplitude low-frequency fluctuation (ALFF). Serum inflammatory markers were measured by a multiplexed flow cytometric assay.

RESULTS: COVID-19 survivors exhibited subjective cognitive decline compared to healthy controls, despite no significant differences in objective cognitive tasks. Structural analysis revealed significantly increased gray matter volume and cortical surface area in the left transverse temporal gyrus (Heschl's gyrus) in quarantined COVID-19 survivors. This enlargement was negatively correlated with cognitive impairment. The ALFF analysis showed decreased neural activity in multiple brain regions. Elevated levels of serum inflammatory markers were also found in COVID-19 survivors, including MIP-1a, MIP-1b, TNF-a, and IL-8, which correlated with functional abnormalities.

CONCLUSIONS: Our findings indicate a subjective cognitive decline in quarantined COVID-19 survivors 15 months after discharge, which is associated with brain structural alterations in the left Heschl's gyrus. The observed elevation of inflammatory markers suggests a potential mechanism involving inflammation-induced neurogenesis. These results contribute to our understanding of the possible mechanisms underlying long-term neuropsychiatric consequences of COVID-19 and highlight the need for further research to develop targeted interventions.}, } @article {pmid38319270, year = {2024}, author = {Nasyrov, RA and Galichina, VA and Timchenko, VN and Krasnogorskaya, OL and Chepelev, AS and Fedotova, EP and Sidorova, NA and Agafonnikova, AA and Anichkov, NM}, title = {[Lung pathology in children with a long-term novel coronavirus infection COVID-19].}, journal = {Arkhiv patologii}, volume = {86}, number = {1}, pages = {36-43}, doi = {10.17116/patol20248601136}, pmid = {38319270}, issn = {0004-1955}, mesh = {Adult ; Humans ; Child ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; Apoptosis ; }, abstract = {UNLABELLED: New coronavirus infection is registered less frequently in children than in adults. Among all patients with COVID-19, the share of children is 8.6%. Clinical practice shows that in children, COVID-19 can be severe and even fatal. Articles have been published reflecting the clinical manifestations of Long Covid in children, while data on pathomorphological examination of the lungs during long-term COVID-19 in children are not available in the literature. On the basis of the Department of Pathological Anatomy with a course of Forensic Medicine and the Pathological-Anatomical Department of the Clinic of St. Petersburg State Pediatric Medical University, an analysis of medical documentation was carried out, autopsy materials were selected from 3 observations of the death of children from COVID-19. The selection criterion was the duration of the disease. A histological examination using standard methods and IHC analysis using antibodies to the nucleocapsid of SARS-Cov-2, CD95, CD31 were carried out on the lung tissue of 3 children aged 2 months to 2 years who died from a new coronavirus infection. Microscopically, all three patients showed microvessels damage, their thrombosis, angiogenesis, as well as signs of diffuse alveolar damage The combination of expression of the SARS-CoV-2 nucleocapsid and the apoptosis marker on the vascular endothelium of the MCR is of interest.

CONCLUSION: The data obtained indicate infection with coronavirus and death of endothelial cells due to apoptosis. Endothelial damage in the microvessels of the lungs is the initiating factor in the development of capillary-alveolar block, tissue hypoxia, and disseminated intravascular coagulation syndrome, leading in some cases to respiratory/multiple organ failure and death.}, } @article {pmid38318198, year = {2024}, author = {Sidky, H and Hansen, KA and Girvin, AT and Hotaling, N and Michael, SG and Gersing, K and Sahner, DK and , }, title = {Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19.}, journal = {Computational and structural biotechnology journal}, volume = {24}, number = {}, pages = {115-125}, pmid = {38318198}, issn = {2001-0370}, support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UM1 TR004556/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking.

MATERIALS AND METHODS: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code.

RESULTS: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10[-4]) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.}, } @article {pmid38318183, year = {2024}, author = {Leung, JM and Wu, MJ and Kheradpour, P and Chen, C and Drake, KA and Tong, G and Ridaura, VK and Zisser, HC and Conrad, WA and Hudson, N and Allen, J and Welberry, C and Parsy-Kowalska, C and Macdonald, I and Tapson, VF and Moy, JN and deFilippi, CR and Rosas, IO and Basit, M and Krishnan, JA and Parthasarathy, S and Prabhakar, BS and Salvatore, M and Kim, CC}, title = {Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1348041}, pmid = {38318183}, issn = {1664-3224}, support = {UL1 TR002384/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Immunologic Factors ; Autoantibodies ; Disease Progression ; }, abstract = {BACKGROUND: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.

METHODS: We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.

RESULTS: During the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.

CONCLUSIONS: We found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC.}, } @article {pmid38318123, year = {2024}, author = {Zhao, S and Martin, EM and Reuken, PA and Scholcz, A and Ganse-Dumrath, A and Srowig, A and Utech, I and Kozik, V and Radscheidt, M and Brodoehl, S and Stallmach, A and Schwab, M and Fraser, E and Finke, K and Husain, M}, title = {Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study.}, journal = {EClinicalMedicine}, volume = {68}, number = {}, pages = {102434}, pmid = {38318123}, issn = {2589-5370}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing.

METHODS: To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK.

FINDINGS: We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention.

INTERPRETATION: Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC.

FUNDING: Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).}, } @article {pmid38317942, year = {2024}, author = {Sadat Larijani, M and Banifazl, M and Karami, A and Ramezani, A}, title = {Long-term rheumatoid manifestations as a consequence of COVID-19 and/or vaccination: A case report after a 2-year follow-up.}, journal = {Heliyon}, volume = {10}, number = {3}, pages = {e24982}, pmid = {38317942}, issn = {2405-8440}, abstract = {COVID-19 is now established as a multi-organ involvement disease with a broad range of manifestations. Identification of post-acute COVID-19 incidence is critical according to increasing number of late symptoms reports. Hereby, we report a case with a past history of COVID-19 who presented different manifestations including osteoarticular and neurological involvement within a long-term follow-up. The organs involvement initiated lately after primary vaccinations (with inactivated vaccine) and lasted few months without any pre-existing medical condition. However, upon the completion of the vaccine schedule and receiving a protein subunit vaccine, PastoCovac Plus, as a booster, the symptoms improved substantially and resolved, though in the reinfection episode partial, reoccurrence was recorded. This presentation can be a challenging issue owing to the fact that the majority of global population are vaccinated and also experience COVID-19 in this era and sometimes differentiation between consequences of the virus as post COVID-19 or the vaccination side effects is difficult.}, } @article {pmid38317683, year = {2023}, author = {Malheiro, DT and Bernardez-Pereira, S and Parreira, KCJ and Pagliuso, JGD and de Paula Gomes, E and de Mesquita Escobosa, D and de Araújo, CI and Pimenta, BS and Lin, V and de Almeida, SM and Tuma, P and Laselva, CR and Neto, MC and Klajner, S and Teich, VD and Kobayashi, T and Edmond, MB and Marra, AR}, title = {Prevalence, predictors, and patient-reported outcomes of long COVID in hospitalized and non-hospitalized patients from the city of São Paulo, Brazil.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1302669}, pmid = {38317683}, issn = {2296-2565}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; *Depressive Disorder, Major ; Retrospective Studies ; Brazil/epidemiology ; Prevalence ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND: Robust data comparing long COVID in hospitalized and non-hospitalized patients in middle-income countries are limited.

METHODS: A retrospective cohort study was conducted in Brazil, including hospitalized and non-hospitalized patients. Long COVID was diagnosed at 90-day follow-up using WHO criteria. Demographic and clinical information, including the depression screening scale (PHQ-2) at day 30, was compared between the groups. If the PHQ-2 score is 3 or greater, major depressive disorder is likely. Logistic regression analysis identified predictors and protective factors for long COVID.

RESULTS: A total of 291 hospitalized and 1,118 non-hospitalized patients with COVID-19 were included. The prevalence of long COVID was 47.1% and 49.5%, respectively. Multivariable logistic regression showed female sex (odds ratio [OR] = 4.50, 95% confidence interval (CI) 2.51-8.37), hypertension (OR = 2.90, 95% CI 1.52-5.69), PHQ-2 > 3 (OR = 6.50, 95% CI 1.68-33.4) and corticosteroid use during hospital stay (OR = 2.43, 95% CI 1.20-5.04) as predictors of long COVID in hospitalized patients, while female sex (OR = 2.52, 95% CI 1.95-3.27) and PHQ-2 > 3 (OR = 3.88, 95% CI 2.52-6.16) were predictors in non-hospitalized patients.

CONCLUSION: Long COVID was prevalent in both groups. Positive depression screening at day 30 post-infection can predict long COVID. Early screening of depression helps health staff to identify patients at a higher risk of long COVID, allowing an early diagnosis of the condition.}, } @article {pmid38316434, year = {2024}, author = {Laskowski, NM and Brandt, G and Paslakis, G}, title = {[Gender Inequalities of the COVID-19 Pandemic: A Synthesis of Systematic Reviews with a Focus on Sexual and Gender Minorities].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {74}, number = {2}, pages = {57-69}, doi = {10.1055/a-2228-6244}, pmid = {38316434}, issn = {1439-1058}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; Pandemics ; Gender Equity ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; *Sexual and Gender Minorities ; Gender Identity ; }, abstract = {OBJECTIVE: From the very beginning of the COVID-19 pandemic, gender was shown to play a significant role in how people were affected by it, while aspects related to sexual and gender minorities (SGM) have been rather understudied. The aim of this review was to synthesize systematic reviews and meta-analyses that explicitly addressed the impact of gender within the context of the pandemic, with a focus on SGM.

METHODS: We based the narrative synthesis of results on a literature search of PubMed. We included systematic reviews and meta-analyses as of 2019 with an identifiable gender comparison or SGM reference and a specified clinical outcome.

RESULTS: The search yielded 2 658 hits; 29 systematic reviews were included for content synthesis. Of these, we identified 23 systematic reviews with gender comparisons and 8 related to SGM. Men showed higher prevalence, severity, and mortality of COVID-19 compared with women, but the psychological consequences of the COVID-19 pandemic affected women more compared with men. Evidence suggests that women are at higher risk for Long-COVID-19. SGM experienced increased mental health problems during the COVID-19 pandemic compared to the general population.

DISCUSSION: It appears that biological and social risks led to differential susceptibility to infection and manifestation of COVID-19 disease and also accounted for differences in mortality between men and women. Insights on prevalence, disease burden, and mortality among SGM during the COVID-19 pandemic are lacking. This suggests an underrepresentation of SGM in COVID-19-related research. Despite the abundance of COVID-19 publications, gender effects have not often been explicitly and adequately studied.

CONCLUSION: Future studies should examine gender differences and needs and concerns of SGM in mental disorders and further understudied entities like Long-COVID-19, to gain insights and help to provide preventive measures and adequate treatments for all, for potential future pandemics as well.}, } @article {pmid38315950, year = {2024}, author = {Tandon, P and Abrams, ND and Avula, LR and Carrick, DM and Chander, P and Divi, RL and Dwyer, JT and Gannot, G and Gordiyenko, N and Liu, Q and Moon, K and PrabhuDas, M and Singh, A and Tilahun, ME and Satyamitra, MM and Wang, C and Warren, R and Liu, CH}, title = {Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {212}, number = {4}, pages = {505-512}, doi = {10.4049/jimmunol.2300804}, pmid = {38315950}, issn = {1550-6606}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Inflammation ; Disease Progression ; }, abstract = {As COVID-19 continues, an increasing number of patients develop long COVID symptoms varying in severity that last for weeks, months, or longer. Symptoms commonly include lingering loss of smell and taste, hearing loss, extreme fatigue, and "brain fog." Still, persistent cardiovascular and respiratory problems, muscle weakness, and neurologic issues have also been documented. A major problem is the lack of clear guidelines for diagnosing long COVID. Although some studies suggest that long COVID is due to prolonged inflammation after SARS-CoV-2 infection, the underlying mechanisms remain unclear. The broad range of COVID-19's bodily effects and responses after initial viral infection are also poorly understood. This workshop brought together multidisciplinary experts to showcase and discuss the latest research on long COVID and chronic inflammation that might be associated with the persistent sequelae following COVID-19 infection.}, } @article {pmid38314095, year = {2024}, author = {Perez-Pons, M and Molinero, M and Benítez, ID and García-Hidalgo, MC and Chatterjee, S and Bär, C and González, J and Torres, A and Barbé, F and de Gonzalo-Calvo, D and , }, title = {MicroRNA-centered theranostics for pulmoprotection in critical COVID-19.}, journal = {Molecular therapy. Nucleic acids}, volume = {35}, number = {1}, pages = {102118}, pmid = {38314095}, issn = {2162-2531}, abstract = {Elucidating the pathobiological mechanisms underlying post-acute pulmonary sequelae following SARS-CoV-2 infection is essential for early interventions and patient stratification. Here, we investigated the potential of microRNAs (miRNAs) as theranostic agents for pulmoprotection in critical illness survivors. Multicenter study including 172 ICU survivors. Diffusion impairment was defined as a lung-diffusing capacity for carbon monoxide (DLCO) <80% within 12 months postdischarge. A disease-associated 16-miRNA panel was quantified in plasma samples collected at ICU admission. Bioinformatic analyses were conducted using KEGG, Reactome, GTEx, and Drug-Gene Interaction databases. The results were validated using an external RNA-seq dataset. A 3-miRNA signature linked to diffusion impairment (miR-27a-3p, miR-93-5p, and miR-199a-5p) was identified using random forest. Levels of miR-93-5p and miR-199a-5p were independently associated with the outcome, improving patient classification provided by the electronic health record. The experimentally validated targets of these miRNAs exhibited enrichment across diverse pathways, with telomere length quantification in an additional set of samples (n = 83) supporting the role of cell senescence in sequelae. Analysis of an external dataset refined the pathobiological fingerprint of pulmonary sequelae. Gene-drug interaction analysis revealed four FDA-approved drugs. Overall, this study advances our understanding of lung recovery in postacute respiratory infections, highlighting the potential of miRNAs and their targets for pulmoprotection.}, } @article {pmid38313024, year = {2024}, author = {Titze-de-Almeida, R and Araújo Lacerda, PH and de Oliveira, EP and de Oliveira, MEF and Vianna, YSS and Costa, AM and Pereira Dos Santos, E and Guérard, LMC and Ferreira, MAM and Rodrigues Dos Santos, IC and Gonçalves, JDDS and Ginani Ferreira, G and Souza Titze-de-Almeida, S and Brandão, PRP and Eri Shimizu, H and Silva, APB and Delgado-Rodrigues, RN and , }, title = {Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e16669}, pmid = {38313024}, issn = {2167-8359}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Sleep ; Headache/epidemiology ; Dyspnea ; Nausea ; Vomiting ; }, abstract = {This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.}, } @article {pmid38312039, year = {2024}, author = {Vakani, K and Ratto, M and Sandford-James, A and Antonova, E and Kumari, V}, title = {Cognitive and mental health trajectories of COVID-19: Role of hospitalisation and long-COVID symptoms.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {67}, number = {1}, pages = {e17}, pmid = {38312039}, issn = {1778-3585}, mesh = {Adult ; Middle Aged ; Humans ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cognition ; Hospitalization ; }, abstract = {BACKGROUND: There is considerable evidence of cognitive impairment post COVID-19, especially in individuals with long-COVID symptoms, but limited research objectively evaluating whether such impairment attenuates or resolves over time, especially in young and middle-aged adults.

METHODS: Follow-up assessments (T2) of cognitive function (processing speed, attention, working memory, executive function, memory) and mental health were conducted in 138 adults (18-69 years) who had been assessed 6 months earlier (T1). Of these, 88 had a confirmed history of COVID-19 at T1 assessment (≥20 days post-diagnosis) and were also followed-up on COVID-19-related symptoms (acute and long-COVID); 50 adults had no known COVID-19 history at any point up to their T2 assessment.

RESULTS: From T1 to T2, a trend-level improvement occurred in intra-individual variability in processing speed in the COVID, relative to the non-COVID group. However, longer response/task completion times persisted in participants with COVID-19-related hospitalisation relative to those without COVID-19-related hospitalisation and non-COVID controls. There was a significant reduction in long-COVID symptom load, which correlated with improved executive function in non-hospitalised COVID-19 participants. The COVID group continued to self-report poorer mental health, irrespective of hospitalisation history, relative to non-COVID group.

CONCLUSIONS: Although some cognitive improvement has occurred over a 6-month period in young and middle-aged COVID-19 survivors, cognitive impairment persists in those with a history of COVID-19-related hospitalisation and/or long-COVID symptoms. Continuous follow-up assessments are required to determine whether cognitive function improves or possibly worsens, over time in hospitalised and long-COVID participants.}, } @article {pmid38311905, year = {2024}, author = {Nishimi, K and Neylan, TC and Bertenthal, D and Seal, KH and O'Donovan, A}, title = {Association of psychiatric disorders with clinical diagnosis of long COVID in US veterans.}, journal = {Psychological medicine}, volume = {54}, number = {9}, pages = {2024-2032}, pmid = {38311905}, issn = {1469-8978}, support = {IK2 CX002627/CX/CSRD VA/United States ; RES 13-457/RD/ORD VA/United States ; Faculty Resource Fund Award//University of California, San Francisco/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology/psychology ; *Mental Disorders/epidemiology ; United States/epidemiology ; Retrospective Studies ; *Veterans/statistics & numerical data/psychology ; Adult ; Aged ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Comorbidity ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID.

METHODS: We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations.

RESULTS: Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21-1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36-1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78-0.88).

CONCLUSIONS: Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.}, } @article {pmid38311899, year = {2024}, author = {Nguyen, KH and Chen, S and Bao, Y and Lu, Y and Bednarczyk, RA and Vasudevan, L}, title = {COVID-19 Diagnosis, Severity, and Long COVID Among U.S. Adolescents, National Health Interview Survey, 2022.}, journal = {American journal of health promotion : AJHP}, volume = {38}, number = {4}, pages = {534-539}, doi = {10.1177/08901171241231642}, pmid = {38311899}, issn = {2168-6602}, support = {R37 CA234119/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Child ; Adolescent ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology ; COVID-19 Vaccines ; COVID-19 Testing ; Cross-Sectional Studies ; Vaccination ; }, abstract = {PURPOSE: Understanding disparities in COVID-19 outcomes, overall and stratified by vaccination status, is important for developing targeted strategies to increase vaccination coverage and protect adolescents from COVID-19.

DESIGN: The 2022 National Health Interview Survey (NHIS) is a cross-sectional nationally representative household survey of U.S. adults.

SETTING: A probability sample of households in the U.S.

SAMPLE: One child aged 12-17 years is randomly selected from each family in the household. A knowledgeable adult (eg, parent or guardian), responds on behalf of the child through an in-person interview (response rate = 49.9%).

MEASURES: Input measures-sociodemographic characteristics and COVID-19 vaccination status; output measures-ever had COVID-19, moderate/severe COVID-19, long COVID.

ANALYSIS: Prevalence of COVID-19 outcomes was assessed for adolescents aged 12-17 years. Factors associated with each COVID-19 outcome were assessed with multivariable logistic regression analyses.

RESULTS: Among 2758 adolescents aged 12-17 years in 2022, 60.5% had received ≥1 dose of COVID-19 vaccine, 30.2% had ever been diagnosed by a doctor that they had COVID-19, 29.5% had moderate/severe COVID-19, and 6.2% had long COVID. Adolescents who were vaccinated with ≥1 dose were less likely to be diagnosed with COVID-19 (aOR = .79) and less likely to have long COVID (aOR = .30).

CONCLUSION: Targeted messaging to highlight the importance of early treatment, the harms of long COVID-19, and the benefits of vaccination in protecting against long-term effects may be necessary to ensure that all adolescents and their families are adequately protected.}, } @article {pmid38310391, year = {2024}, author = {Zhao, W and Wang, S and Han, Y and Zhang, H and Cao, J and Dong, S and Li, D and Lei, M and Liu, C and Gao, Y}, title = {Role of Ferroptosis in the Progression of COVID-19 and the Development of Long COVID.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673281662231208102354}, pmid = {38310391}, issn = {1875-533X}, abstract = {OBJECTIVES: To examine the role of ferroptosis on the pathogenesis and progression of COVID-19.

MATERIALS AND METHODS: A total of 127 patients who were hospitalized for COVID-19 were categorized into two groups according to the intensity of oxygen therapy (high-flow or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one or two weeks after treatment. Telephone follow-up was performed 3 months after discharge to assess long COVID.

RESULTS: Patients receiving high-flow oxygen therapy had greater levels of neutrophils; D-dimer; C reactive protein; procalcitonin; plasma protein levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-17, and acyl-CoA synthetase long-chain family member 4 (ACSL4); and PBMC mRNA level of TNF-α; but had lower levels of lymphocytes and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and IL-17, and positive correlations of ACSL4 with inflammatory markers in plasma and PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower after treatment than at baseline, but there were higher post-treatment levels of lymphocytes, GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of plasma SLC7A11.

CONCLUSION: Ferroptosis is activated during the progression of COVID-19, and a low baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as a therapeutic target.}, } @article {pmid38309813, year = {2024}, author = {Kell, DB and Khan, MA and Laubscher, GJ and Pretorius, E}, title = {Uncertainties about the roles of anticoagulation and microclots in postacute sequelae of SARS-CoV-2 infection: comment from Kell et al.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {22}, number = {2}, pages = {565-568}, doi = {10.1016/j.jtha.2023.09.035}, pmid = {38309813}, issn = {1538-7836}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Blood Coagulation ; Anticoagulants/therapeutic use ; }, } @article {pmid38309763, year = {2024}, author = {Zhang, Y and Chinchilli, VM and Ssentongo, P and Ba, DM}, title = {Association of Long COVID with mental health disorders: a retrospective cohort study using real-world data from the USA.}, journal = {BMJ open}, volume = {14}, number = {2}, pages = {e079267}, pmid = {38309763}, issn = {2044-6055}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Retrospective Studies ; Mental Health ; Cohort Studies ; SARS-CoV-2 ; *Mental Disorders/epidemiology ; }, abstract = {OBJECTIVES: Mental health disorders (MHD) rank third for US adult hospitalisations. Given the substantial prevalence of 'Long COVID' in SARS-CoV-2 survivors, this study aims to assess its association with increased MHD risk using extensive real-world data.

DESIGN: A retrospective cohort study with propensity score matching was conducted. We used the International Classification of Diseases, 10th Revision codes to identify individuals with Long COVID status and COVID-19 histories. Multivariable stratified Cox proportional hazards regression analysis was conducted to determine the association of Long COVID status with MHD.

SETTING: Data were sourced from the TriNetX database, spanning records from 1 October 2021 to 16 April 2023.

PARTICIPANTS: Two distinct cohorts were established: one comprising individuals diagnosed with Long COVID and another comprising individuals with no history of Long COVID or COVID-19. At the start of the study, none of the participants had a recorded MHD.

The main outcome of interest was a composite diagnosis of MHD. Secondary outcomes were individual mental health conditions.

RESULTS: The study included 43 060 control participants without Long COVID and 4306 Long COVID participants, demonstrating well-balanced distribution across all covariates. After adjusting for 4 demographic factors and 10 comorbidities, Long COVID was associated with MHD (adjusted HR, aHR 2.60; 95% CI 2.37 to 2.85). In subgroup analysis, Long COVID was associated with major depression disorder (aHR 3.36; 95% CI 2.82 to 4.00) and generalised anxiety disorder (aHR 3.44; 95% CI 2.99 to 3.96).

CONCLUSIONS: In this retrospective large real-world cohort study, Long COVID was associated with an increased risk of incident MHD. The MHD impact is significant considering the vast number of patients with Long COVID. Enhanced MHD screening among COVID-19 survivors should be a priority.}, } @article {pmid38308511, year = {2024}, author = {Osiaevi, I and Kümpers, P and Weinmann-Menke, J and Pavenstädt, H and Rovas, A}, title = {Capillary rarefication as a possible cause of long-COVID syndrome.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {39}, number = {8}, pages = {1214-1217}, doi = {10.1093/ndt/gfae026}, pmid = {38308511}, issn = {1460-2385}, support = {//Servier/ ; }, mesh = {Humans ; Capillaries/pathology ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; }, } @article {pmid38308155, year = {2024}, author = {MacEwan, SR and Rahurkar, S and Tarver, WL and Forward, C and Eramo, JL and Teuschler, L and Gaughan, AA and Rush, LJ and Stanwick, S and McConnell, E and Schamess, A and McAlearney, AS}, title = {Patient Experiences Navigating Care Coordination For Long COVID: A Qualitative Study.}, journal = {Journal of general internal medicine}, volume = {39}, number = {8}, pages = {1294-1300}, pmid = {38308155}, issn = {1525-1497}, support = {U54 CA260582/CA/NCI NIH HHS/United States ; U54CA260582/CA/NCI NIH HHS/United States ; U54CA260582/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/therapy/epidemiology ; Male ; Female ; *Qualitative Research ; Middle Aged ; Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Continuity of Patient Care/organization & administration ; SARS-CoV-2 ; Health Services Accessibility/organization & administration ; Patient Navigation/organization & administration ; }, abstract = {BACKGROUND: Little is known about how to best evaluate, diagnose, and treat long COVID, which presents challenges for patients as they seek care.

OBJECTIVE: Understand experiences of patients as they navigate care for long COVID.

DESIGN: Qualitative study involving interviews with patients about topics related to seeking and receiving care for long COVID.

PARTICIPANTS: Eligible patients were at least 18 years of age, spoke English, self-identified as functioning well prior to COVID infection, and reported long COVID symptoms continued to impact their lives at 3 months or more after a COVID infection.

APPROACH: Patients were recruited from a post-COVID recovery clinic at an academic medical center from August to September 2022. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.

KEY RESULTS: Participants (n=21) reported experiences related to elements of care coordination: access to care, evaluation, treatment, and ongoing care concerns. Some patients noted access to care was facilitated by having providers that listened to and validated their symptoms; other patients reported feeling their access to care was hindered by providers who did not believe or understand their symptoms. Patients reported confusion around how to communicate their symptoms when being evaluated for long COVID, and they expressed frustration with receiving test results that were normal or diagnoses that were not directly attributed to long COVID. Patients acknowledged that clinicians are still learning how to treat long COVID, and they voiced appreciation for providers who are willing to try new treatment approaches. Patients expressed ongoing care concerns, including feeling there is nothing more that can be done, and questioned long-term impacts on their aging and life expectancy.

CONCLUSIONS: Our findings shed light on challenges faced by patients with long COVID as they seek care. Healthcare systems and providers should consider these challenges when developing strategies to improve care coordination for patients with long COVID.}, } @article {pmid38307886, year = {2024}, author = {Romero-Ibarguengoitia, ME and Rodríguez-Torres, JF and Garza-Silva, A and Rivera-Cavazos, A and Morales-Rodriguez, DP and Hurtado-Cabrera, M and Kalife-Assad, R and Villarreal-Parra, D and Loose-Esparza, A and Gutiérrez-Arias, JJ and Mata-Porras, YG and Ojeda-Salazar, DA and Sanz-Sánchez, MA and González-Cantú, A and Azzolini, E and Rescigno, M}, title = {Association of vaccine status, reinfections, and risk factors with Long COVID syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2817}, pmid = {38307886}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; Adult ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Reinfection ; Pandemics ; Risk Factors ; Vaccination ; }, abstract = {The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients' comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment. Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05). Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor. We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.}, } @article {pmid38306758, year = {2024}, author = {Ahmed, S and Ahmad, E and Ahmad, B and Arif, MH and Ilyas, HMA and Hashmi, N and Ahmad, S}, title = {Long COVID-19 and primary care: Challenges, management and recommendations.}, journal = {Semergen}, volume = {50}, number = {3}, pages = {102188}, doi = {10.1016/j.semerg.2023.102188}, pmid = {38306758}, issn = {1578-8865}, mesh = {Humans ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chronic Disease ; Primary Health Care ; Disease Progression ; }, abstract = {Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms after COVID-19 onset. This article explores the challenges, management strategies, and recommendations for addressing long COVID-19 in primary care settings. The epidemiology of long COVID-19 reveals significant variability, with a substantial portion of COVID-19 survivors experiencing post-acute symptoms. Pathophysiological mechanisms include viral persistence, endothelial dysfunction, autoimmunity, neurological dysregulation, and gastrointestinal dysbiosis. Multiple risk factors, including age, sex, pre-existing comorbidities, smoking, BMI, and acute COVID-19 severity, influence the development of long COVID-19. Effective management requires proactive measures such as vaccination, identification of high-risk populations, public awareness, and post-infection vaccination. Collaboration of primary care physicians with specialists is essential for holistic and individualized patient care. This article underscores the role of primary care physicians in diagnosing, managing, and mitigating the long-term effects of COVID-19.}, } @article {pmid38305629, year = {2024}, author = {Listed, NA}, title = {Expression of Concern.}, journal = {European review for medical and pharmacological sciences}, volume = {28}, number = {2}, pages = {445}, doi = {10.26355/eurrev_202401_35160}, pmid = {38305629}, issn = {2284-0729}, abstract = {The Editor in Chief and the Publisher are issuing an expression of concern to alert readers to the fact that the Special Issue titled "Omics sciences in the personalization of diagnosis and therapy" and, in particular, the following articles: · J. Kaftalli, K. Donato, G. Bonetti, K. Dhuli, A. Macchia, P.E. Maltese, K. Louise Herbst, S. Michelini, P. Chiurazzi, M. Hill, S. Michelini, S. Michelini, G. Marceddu, A. Bernini, M. Bertelli. Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 127-136. DOI: 10.26355/eurrev_202312_34697-PMID: 38112953. · M.C. Medori, K. Donato, L. Stuppia, T. Beccari, M. Dundar, R.S. Marks, S. Michelini, E. Borghetti, C. Zuccato, L. Seppilli, H. Elsangak, G. Sozanski, D. Malacarne, M. Bertelli. Achievement of sustainable development goals through the Mediterranean diet. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 89-99. DOI: 10.26355/eurrev_202312_34693-PMID: 38112950. · K. Donato, M.C. Medori, A. Macchia, S. Cecchin, M.R. Ceccarini, T. Beccari, V. Gatta, L. Stuppia, V. Benfatti, L. Dalla Ragione, P. Chiurazzi C. Micheletti, K. Dhuli, G. Madeo, G. Bonetti, G. Marceddu, M. Bertelli. Genetic variants identified in novel candidate genes for anorexia nervosa and analysis of molecular pathways for diagnostic applications. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 77-88. DOI: 10.26355/eurrev_202312_34692-PMID: 38112957. · K. Donato, K. Dhuli, A. Macchia, M.C. Medori, C. Micheletti, G. Bonetti, M.R. Ceccarini, T. Beccari, P. Chiurazzi, S. Cristoni, V. Benfatti, L. Dalla Ragione, M. Bertelli. Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 64-76. DOI: 10.26355/eurrev_202312_34691-PMID: 38112949. · M.R. Ceccarini, M.C. Medori, K. Dhuli, S. Tezzele, G. Bonetti, C. Micheletti, P.E. Maltese, S. Cecchin, K. Donato, L. Colombo, L. Rossetti, G. Staurenghi, A.P. Salvetti, M. Oldani, L. Ziccardi, D. Marangoni, G. Iarossi, B. Falsini, G. Placidi, F. D'Esposito, F. Viola, M. Nassisi, G. Leone, L. Cimino, L. De Simone, V. Mastrofilippo, T. Beccari, M. Bertelli. Autoantibodies detection in patients affected by autoimmune retinopathies. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 57-63. DOI: 10.26355/eurrev_202312_34690-PMID: 38112948. · E. Kalluçi, E. Noka, K. Bani, X. Dhamo, I. Alimehmeti, K. Dhuli, G. Madeo, C. Micheletti, G. Bonetti, C. Zuccato, E. Borghetti, G. Marceddu, M. Bertelli. Correlation between COVID-19 and air pollution: the effects of PM2.5 and PM10 on COVID-19 outcomes. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 39-47. DOI: 10.26355/eurrev_202312_34688-PMID: 38112947. · K. Dhuli, C. Micheletti, M.C. Medori, G. Madeo, G. Bonetti, K. Donato, F. Gaffuri, G.M. Tartaglia, S. Michelini, A. Fiorentino, D. Cesarz, S.T. Connelly, N. Capodicasa, M. Bertelli. The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 33-38. DOI: 10.26355/eurrev_202312_34687-PMID: 38112946. · K. Dhuli, M.C. Medori, C. Micheletti, K. Donato, F. Fioretti, A. Calzoni, A. Praderio, M.G. De Angelis, G. Arabia, S. Cristoni, S. Nodari, M. Bertelli. Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome. Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 13-19. DOI: 10.26355/eurrev_202312_34685-PMID: 38112944. are being reviewed again after publication by an independent Editor and a new group of reviewers due to concerns raised by readers on PubPeer regarding an undisclosed authors' conflict of interest and methodological issues of some articles. Further updates will be provided once the investigation is completed. The authors have been notified about this expression of concern.}, } @article {pmid38304426, year = {2024}, author = {Saito, S and Shahbaz, S and Luo, X and Osman, M and Redmond, D and Cohen Tervaert, JW and Li, L and Elahi, S}, title = {Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1341843}, pmid = {38304426}, issn = {1664-3224}, mesh = {Male ; Humans ; Female ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Acute Disease ; Quality of Life ; Sarcosine ; SARS-CoV-2 ; *COVID-19 ; Biomarkers ; Serine ; }, abstract = {INTRODUCTION: A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.

METHODS: We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).

RESULTS: Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.

CONCLUSION: Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.}, } @article {pmid38303065, year = {2024}, author = {Scott, A and Ansari, W and Khan, F and Chambers, R and Benigno, M and Di Fusco, M and McGrath, L and Malhotra, D and Draica, F and Nguyen, J and Atkinson, J and Atwell, JE}, title = {Substantial health and economic burden of COVID-19 during the year after acute illness among US adults at high risk of severe COVID-19.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {46}, pmid = {38303065}, issn = {1741-7015}, mesh = {Adult ; Humans ; United States/epidemiology ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Financial Stress ; Acute Disease ; COVID-19 Testing ; SARS-CoV-2 ; Retrospective Studies ; }, abstract = {BACKGROUND: Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19.

METHODS: Eligible adults were diagnosed with COVID-19 from April 1 to May 31, 2020, had ≥ 1 condition placing them at risk of severe COVID-19, and were enrolled in Optum's de-identified Clinformatics[®] Data Mart Database for ≥ 12 months before and ≥ 13 months after COVID-19 diagnosis. Percentages of diagnoses, medications, resource use, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified by age and COVID-19 severity.

RESULTS: The cohort included 19,558 patients (aged 18-64 y, n = 9381; aged ≥ 65 y, n = 10,177). Compared with baseline, patients during the post-acute phase had increased percentages of blood disorders (16.3%), nervous system disorders (11.1%), and mental and behavioral disorders (7.7%), along with increases in related prescriptions. Overall, there were substantial increases in inpatient and outpatient healthcare utilization, along with a 23.0% increase in medical costs. Changes were greatest among older patients and those admitted to the intensive care unit for acute COVID-19 but were also observed in younger patients and those who did not require COVID-19 hospitalization.

CONCLUSIONS: There is a significant clinical and economic burden of post-COVID conditions among US individuals at high risk for severe COVID-19.}, } @article {pmid38302974, year = {2024}, author = {Pazukhina, E and Rumyantsev, M and Baimukhambetova, D and Bondarenko, E and Markina, N and El-Taravi, Y and Petrova, P and Ezhova, A and Andreeva, M and Iakovleva, E and Bobkova, P and Pikuza, M and Trefilova, A and Abdeeva, E and Galiautdinova, A and Filippova, Y and Bairashevskaia, A and Zolotarev, A and Bulanov, N and DunnGalvin, A and Chernyavskaya, A and Kondrikova, E and Kolotilina, A and Gadetskaya, S and Ivanova, YV and Turina, I and Eremeeva, A and Fedorova, LA and Comberiati, P and Peroni, DG and Nekliudov, N and Genuneit, J and Reyes, LF and Brackel, CLH and Mazankova, L and Miroshina, A and Samitova, E and Borzakova, S and Carson, G and Sigfrid, L and Scott, JT and McFarland, S and Greenhawt, M and Buonsenso, D and Semple, MG and Warner, JO and Olliaro, P and Osmanov, IM and Korsunskiy, AA and Munblit, D and , }, title = {Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {48}, pmid = {38302974}, issn = {1741-7015}, support = {MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_00034/6/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Child ; Adolescent ; Moscow/epidemiology ; *Post-Acute COVID-19 Syndrome ; Incidence ; Prospective Studies ; SARS-CoV-2 ; *COVID-19/epidemiology ; Aftercare ; Cohort Studies ; Pandemics ; Patient Discharge ; Chronic Disease ; Fatigue ; }, abstract = {BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections.

METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC.

RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts.

CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.}, } @article {pmid38302946, year = {2024}, author = {Wang, H and Lu, F and Ni, X and Luo, R and Chen, L and Yuan, J and Zhang, Z and Lv, Q}, title = {Acute and persistent symptoms of COVID-19 infection in school-aged children: a retrospective study from China.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {344}, pmid = {38302946}, issn = {1471-2458}, support = {JCYJ202103241154-11030//The Key Project of Shenzhen Science and Technology Innovation Commission/ ; JCYJ202103241154-11030//The Key Project of Shenzhen Science and Technology Innovation Commission/ ; JCYJ202103241154-11030//The Key Project of Shenzhen Science and Technology Innovation Commission/ ; SZXK064//Shenzhen Key Medical Discipline Construction Fund/ ; SZXK064//Shenzhen Key Medical Discipline Construction Fund/ ; SZXK064//Shenzhen Key Medical Discipline Construction Fund/ ; SZSM202011008//Shenzhen San-Ming Project of Medicine in Shenzhen/ ; SZSM202011008//Shenzhen San-Ming Project of Medicine in Shenzhen/ ; SZSM202011008//Shenzhen San-Ming Project of Medicine in Shenzhen/ ; }, mesh = {Child ; Humans ; *COVID-19/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Cross-Sectional Studies ; Comorbidity ; China/epidemiology ; }, abstract = {BACKGROUND: The long-term sequelae of Coronavirus disease 2019 (COVID-19) in children are unclear. We investigated COVID-19 symptoms in school-aged children to determine their impact on patients and their families.

METHODS: This cross-sectional study, conducted on February 25-28, 2023, selected a representative kindergarten and 9-year school from Shenzhen, China. There were randomly two classes each for the 12 grades from kindergarten to junior high school. The school-aged children were aged 3-16 years. Literate parents completed an online questionnaire related to their children's COVID-19 symptoms since December 1, 2022. Descriptive statistics were computed as necessary. Univariate and multivariable linear regression analyses were performed, and variables with a p-value < 0.05 were considered to have a significant association with the subjective feeling scores for COVID-19 infection.

RESULTS: We included 936 school-aged children, with a COVID-19 infection rate of 68.5%. The prevalence of LC 28 (illness with symptoms lasting for 28 days) was 3.4%. During acute infection, the median number of the 641 children's symptoms was 3.0 (IQR: 1.0-5.0) and the median score of subjective feelings was 15.0 (IQR: 11.0-24.5). The top three symptoms were fever, cough/expectoration, and rhinobyon. Age of 13-16 years (adjusted beta: 3.60, 95% CI: 0.32-6.88) and comorbidities (adjusted beta: 3.47, 95% CI: 1.20-5.73) were independently associated with higher subjective feelings (p < 0.05). The top three characteristics associated with LC 28 were alopecia (33.3%, 5/15), cognitive dysfunction (29.2%, 7/24), and emotional problem (28.6%, 6/21).

CONCLUSIONS: Children with COVID-19 have a short duration of symptoms and milder symptoms, so they can self-medicate to minimize hospital crowding. Children with basic diseases require prompt attention. Although LC 28 is uncommon in children, mental and psychological problems after COVID-19 recovery should not be ignored.}, } @article {pmid38302942, year = {2024}, author = {Scott, A and Ansari, W and Chambers, R and Reimbaeva, M and Mikolajczyk, T and Benigno, M and Draica, F and Atkinson, J}, title = {Substantial health and economic burden of COVID-19 during the year after acute illness among US adults not at high risk of severe COVID-19.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {47}, pmid = {38302942}, issn = {1741-7015}, mesh = {Adult ; Male ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Financial Stress ; Acute Disease ; COVID-19 Testing ; }, abstract = {BACKGROUND: Patients recovering from SARS-CoV-2 infection and acute COVID-19 illness can experience a range of long-term post-acute effects. The potential clinical and economic burden of these outcomes in the USA is unclear. We evaluated diagnoses, medications, healthcare utilization, and medical costs before and after acute COVID-19 illness in US patients who were not at high risk of severe COVID-19.

METHODS: This study included eligible adults who were diagnosed with COVID-19 from April 1 to May 31, 2020, who were 18 - 64 years of age, and enrolled within Optum's de-identified Clinformatics® Data Mart Database for 12 months before and 13 months after COVID-19 diagnosis. Patients with any condition or risk factor placing them at high risk of progression to severe COVID-19 were excluded. Percentages of diagnoses, medications, healthcare utilization, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified into 3 cohorts according to disposition during acute COVID-19 illness (i.e., not hospitalized, hospitalized without intensive care unit [ICU] admission, or admitted to the ICU).

RESULTS: The study included 3792 patients; 56.5% of patients were men, 44% were White, and 94% did not require hospitalization. Compared with baseline, patients during the post-acute phase had percentage increases in the diagnosis of the following disorders: blood (166%), endocrine and metabolic (123%), nervous system (115%), digestive system (76%), and mental and behavioral (75%), along with increases in related prescriptions. Substantial increases in all measures of healthcare utilization were observed among all 3 cohorts. Total medical costs increased by 178% during the post-acute phase. Those who were hospitalized with or without ICU admission during the acute phase had the greatest increases in comorbidities and healthcare resource utilization. However, the burden was apparent across all cohorts.

CONCLUSIONS: As evidenced by resource use in the post-acute phase, COVID-19 places a significant long-term clinical and economic burden among US individuals, even among patients whose acute infection did not merit hospitalization.}, } @article {pmid38302141, year = {2024}, author = {Ladds, E and Darbyshire, JL and Bakerly, ND and Falope, Z and Tucker-Bell, I}, title = {Cognitive dysfunction after covid-19.}, journal = {BMJ (Clinical research ed.)}, volume = {384}, number = {}, pages = {e075387}, doi = {10.1136/bmj-2023-075387}, pmid = {38302141}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; *Cognitive Dysfunction/etiology ; Cognition ; }, } @article {pmid38299800, year = {2024}, author = {Whiteside, DM and Basso, MR and Shen, C and Fry, L and Naini, S and Waldron, EJ and Holker, E and Porter, J and Eskridge, C and Logemann, A and Minor, GN}, title = {The relationship between performance validity testing, external incentives, and cognitive functioning in long COVID.}, journal = {Journal of clinical and experimental neuropsychology}, volume = {46}, number = {1}, pages = {6-15}, doi = {10.1080/13803395.2024.2312625}, pmid = {38299800}, issn = {1744-411X}, mesh = {Humans ; Female ; Male ; Middle Aged ; *Neuropsychological Tests/standards ; *COVID-19/complications ; *Motivation/physiology ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Cognitive Dysfunction/etiology/diagnosis/physiopathology ; Cognition/physiology ; Reproducibility of Results ; }, abstract = {INTRODUCTION: Performance validity test (PVT) failures occur in clinical practice and at higher rates with external incentives. However, little PVT research has been applied to the Long COVID population. This study aims to address this gap.

METHODS: Participants were 247 consecutive individuals with Long COVID seen for neuropsychological evaluation who completed 4 PVTs and a standardized neuropsychological battery. The sample was 84.2% White and 66% female. The mean age was 51.16 years and mean education was 14.75 years. Medical records were searched for external incentive (e.g., disability claims). Three groups were created based on PVT failures (Pass [no failures], Intermediate [1 failure], and Fail [2+ failures]).

RESULTS: A total of 8.9% participants failed 2+ PVTs, 6.4% failed one PVT, and 85% passed PVTs. From the full sample, 25.1% were identified with external incentive. However, there was a significant difference between the rates of external incentives in the Fail group (54.5%) compared to the Pass (22.1%) and Intermediate (20%) groups. Further, the Fail group had lower cognitive scores and higher frequency of impaired range scores, consistent with PVT research in other populations. External incentives were uncorrelated with cognitive performance.

CONCLUSIONS: Consistent with other populations, results suggest Long COVID cases are not immune to PVT failure and external incentives are associated with PVT failure. Results indicated that individuals in the Pass and Intermediate groups showed no evidence for significant cognitive deficits, but the Fail group had significantly poorer cognitive performance. Thus, PVTs should be routinely administered in Long COVID cases and research.}, } @article {pmid38299237, year = {2024}, author = {Lempesis, IG and Georgakopoulou, VE and Reiter, RJ and Spandidos, DA}, title = {A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review).}, journal = {International journal of molecular medicine}, volume = {53}, number = {3}, pages = {}, pmid = {38299237}, issn = {1791-244X}, mesh = {Humans ; Antioxidants/pharmacology/therapeutic use/metabolism ; *COVID-19 ; *Melatonin/pharmacology/therapeutic use/metabolism ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/metabolism ; }, abstract = {Coronavirus disease 2019 (COVID‑19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS‑CoV‑2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS‑CoV‑2 infection due to its good safety characteristics and broad‑spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep‑wake cycle and circadian rhythms. It exhibits oncostatic, anti‑inflammatory, antioxidant and anti‑aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID‑19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well‑established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID‑19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID‑19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.}, } @article {pmid38298902, year = {2024}, author = {Zhang, W and Gorelik, AJ and Wang, Q and Norton, SA and Hershey, T and Agrawal, A and Bijsterbosch, JD and Bogdan, R}, title = {Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.}, journal = {Brain, behavior, & immunity - health}, volume = {36}, number = {}, pages = {100722}, pmid = {38298902}, issn = {2666-3546}, abstract = {COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N = 416 including n = 224 COVID-19 cases; Mage = 58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF). We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing. COVID-19 case status was not significantly associated with DBSI-RF (|β|'s < 0.28, pFDR >0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (β's > 0.3, all pFDR = 0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology. Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.}, } @article {pmid38298551, year = {2024}, author = {Corrado, J and Iftekhar, N and Halpin, S and Li, M and Tarrant, R and Grimaldi, J and Simms, A and O'Connor, RJ and Casson, A and Sivan, M}, title = {HEART Rate Variability Biofeedback for LOng COVID Dysautonomia (HEARTLOC): Results of a Feasibility Study.}, journal = {Advances in rehabilitation science and practice}, volume = {13}, number = {}, pages = {27536351241227261}, pmid = {38298551}, issn = {2753-6351}, abstract = {INTRODUCTION: Post-COVID-19 syndrome, or Long Covid (LC) refers to symptoms persisting 12 weeks after the COVID-19 infection. LC comprises a wide range of dysautonomia symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. This study tested the feasibility and estimated the efficacy, of a Heart Rate Variability Biofeedback (HRV-B) programme via a standardised slow diaphragmatic breathing technique in individuals with LC.

METHODS: LC patients underwent a 4-week HRV-B intervention for 10 minutes twice daily for 4 weeks using the Polar H10 ECG (Electrocardiogram) chest strap and Elite HRV phone application. Outcome measures C19-YRSm (Yorkshire Rehabilitation Scale modified), Composite Autonomic Symptom Score (COMPASS-31), WHO Disability Assessment Schedule (WHODAS), EQ5D-5L (EuroQol 5 Dimensions) and Root Mean Square of Successive Differences between heartbeats (RMSSD) using a Fitbit device were recorded before and after the intervention. The study was pre-registered at clinicaltrials.gov NCT05228665.

RESULTS: A total of 13 participants (54% female, 46% male) completed the study with high levels of independent use of technology, data completeness and intervention adherence. There was a statistically significant improvement in C19YRS-m (P = .001), COMPASS-31 (P = .007), RMSSD (P = .047), WHODAS (P = .02) and EQ5D Global Health Score (P = .009). Qualitative feedback suggested participants could use it independently, were satisfied with the intervention and reported beneficial effects from the intervention.

CONCLUSION: HRV-B using diaphragmatic breathing is a feasible intervention for LC. The small sample size limits generalisability. HRV-B in LC warrants further exploration in a larger randomised controlled study.}, } @article {pmid38298288, year = {2024}, author = {Manna, S and Ghosh Dastidar, S and S, R and Ahluwalia, H and Kaur, M}, title = {Preferential Impairment of Auditory Working Memory in Long COVID: An Observational Study of Undergraduate Medical Students.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51457}, pmid = {38298288}, issn = {2168-8184}, abstract = {Background Long COVID is a multisystem condition with prolonged symptoms that develop after recovery from the COVID-19 infection, often following a mild infection. Few studies have been conducted on cognitive function among medical students after recovery from mild COVID-19. This study aimed to assess the attention span and working memory (WM) capacity of medical students after six months of recovery. Methods A cross-sectional study was performed on 17 young adult medical students who had suffered a mild COVID-19 infection at least six months prior. Eighteen age-matched healthy medical students served as the controls. Audio-visual WM tasks and attention spans were assessed using computerized software for both the cases and controls. Results The mean ages of the case and control were 19.67±1.6 and 20.0±1.2 years, respectively. The most common symptoms among cases were fatigue (33%), weight loss (26%), and nasal stuffiness (13%). The overall proportion of correct responses across all visual and auditory WM tasks (p=0.085) and reaction times (p=0.609) did not differ between the cases and controls. However, the overall target hit rate of the auditory WM task was significantly lower in cases than in controls (p=0.002). This difference was not observed in the visual WM task (p=0.374). Conclusion In the current study, the overall WM functions (visual and auditory combined) and attention span did not differ between cases and controls. However, auditory WM performance was significantly impaired in patients compared with controls, indicating selective impairment of auditory WM in patients with long COVID.}, } @article {pmid38297244, year = {2024}, author = {Fagevik Olsén, M and Lannefors, L and Johansson, EL and Persson, HC}, title = {Variations in respiratory and functional symptoms at four months after hospitalisation due to COVID-19: a cross-sectional study.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {63}, pmid = {38297244}, issn = {1471-2466}, mesh = {Male ; Humans ; Female ; Middle Aged ; *COVID-19 ; Cross-Sectional Studies ; Respiration ; Hospitalization ; Exhalation ; }, abstract = {BACKGROUND: Much remains unknown about complex respiratory symptoms after COVID-19. Here we aimed to describe and analyse patients' various respiratory symptoms 4 months after discharge from hospitalisation for COVID-19, focusing on sex, previous pulmonary disease, and prolonged mechanical ventilation.

METHODS: This cross-sectional study involved five hospitals and included 52 patients with self-assessed respiratory dysfunction at 4 months after discharge from hospitalisation for severe COVID-19. Their average age was 63 years, 38% were women, 15 had a previous diagnosed pulmonary disease, and 29 were current or previous smokers. Additionally, 31 had required intensive care-among whom 21 were intubated and 11 needed mechanical ventilation for ≥20 days. Respiratory function was tested concerning lung volumes, expiratory flow, muscle strength, physical capacity (including concurrent oxygen saturation), thoracic expansion, and respiratory movements.

RESULTS: Among 52 patients, 47 (90%) had one or several objectively measured respiratory function abnormalities. Decreased thoracic expansion was observed in 32 patients (62%), abnormal respiratory movements in 30 (58%), decreased vital capacity in 21 (40%), low physical function in 13 (26%), and desaturation during the test in 9 (17%). Respiratory inspiratory muscle strength was more commonly diminished than expiratory strength (27% vs. 8%). We did not observe differences between men and women, or between patients with versus without diagnosed pulmonary disease, except that those with pulmonary disease had significantly lower physical capacity assessed with 6MWD (70% vs. 88% predicted, p = 0.013). Compared to those who did not, patients who required ≥20 days of mechanical ventilation performed similarly on most tests, except that all thoracic breathing movements were significantly smaller (p < 0.05). The numbers and combinations of abnormal findings varied widely, without clear patterns.

CONCLUSION: Patients with remaining respiratory symptoms 4 months after discharge from hospitalization due to COVID-19 may suffer from various abnormal breathing functions, and dysfunctional breathing that is not detected using traditional measurements. These patients may benefit from multidimensional measuring of breathing movement, thoracic expansion, and respiratory muscle strength, along with traditional measurements, to assess their symptoms and enable prescription of optimal treatment interventions and rehabilitation.

TRIAL REGISTRATION: FoU i Sverige (Research & Development in Sweden, Registration number: 274476, registered 2020-05-28).}, } @article {pmid38297181, year = {2024}, author = {Matsumoto, C}, title = {The necessity of investigations to clarify sex and racial disparities in pathophysiology of Long COVID.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {47}, number = {4}, pages = {984-986}, pmid = {38297181}, issn = {1348-4214}, mesh = {Female ; Humans ; *Calcium Channel Blockers ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38296347, year = {2024}, author = {Dierckx, W and De Backer, W and De Meyer, Y and Lauwers, E and Franck, E and De Backer, J and Ides, K}, title = {Personalized pulmonary rehabilitation program for patients with post-acute sequelae of COVID-19: A proof-of-concept retrospective study.}, journal = {Physiological reports}, volume = {12}, number = {3}, pages = {e15931}, pmid = {38296347}, issn = {2051-817X}, mesh = {Humans ; Adult ; Middle Aged ; Retrospective Studies ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Lung ; *Pulmonary Disease, Chronic Obstructive ; }, abstract = {Long-COVID patients present with a decline in physical fitness. The aim of this study is to reveal the impact of pulmonary rehabilitation (PR) on physical fitness, quality of life (QoL), and parameters of quantified thorax CT. Long-COVID patients enrolled in a 3-month PR program were retrospectively studied. PR included endurance and resistance training three times a week. Assessments pre- and post-rehabilitation included quantified chest CT, pulmonary function tests (PFT), six-minute walk test (6MWT), cardiopulmonary exercise test, and questionnaires: Hospital Anxiety and Depression Scale, post-COVID-19 Functional Status scale, Borg score, and EuroQol. Seventeen subjects (5M/12F), mean age 42 ± 13 years, were included. PR improved all questionnaires' results significantly. Only significant difference in PFT parameters was correlation between baseline total lung capacity (TLC) and difference in TLC pre- and post-rehabilitation (p = 0.002). 6MWT increased from 329 to 365 m (p < 0.001), VO2max changed from 21 to 24 mL/kg/min (p = 0.007), peak load increased from 116 to 141 Watt (p < 0.001). Blood volume in small pulmonary vessels of 1.25 to 5 mm[2] in cross-sectional area (BV5%) was higher than observed in patients with acute COVID-19 infection. After rehabilitation, BV5% decreased from 65% to 62% (p = 0.020). These changes correlated directly with changes in TLC (p = 0.039). Quantified CT airway volume increased after rehabilitation (p = 0.013). After rehabilitation, TLC tended to normalize due to (re)opening of small airways, with decline in air trapping and recruitment of alveoli. Furthermore, this study revealed that pulmonary rehabilitation can improve QoL and physical fitness in long-COVID patients.}, } @article {pmid38294616, year = {2024}, author = {Kelleni, MT}, title = {Repurposing metformin to manage idiopathic or long COVID Tinnitus: self-report adopting a pathophysiological and pharmacological approach.}, journal = {Inflammopharmacology}, volume = {32}, number = {2}, pages = {945-948}, pmid = {38294616}, issn = {1568-5608}, mesh = {Male ; Humans ; Self Report ; Post-Acute COVID-19 Syndrome ; *Tinnitus/drug therapy ; *COVID-19 ; }, abstract = {Chronic tinnitus is a common neurological disorder that affects millions of patients globally with no available successful pharmacotherapy. It can be extremely bothersome to some patients to the extent that it occasionally qualifies as a disability that can hinder them from leading a normal life. In this short communication, the author discusses how he suffered from idiopathic tinnitus and how he managed to adopt a combined pathophysiological and pharmacological approach to the reason for the first time in the medical literature that low-dose metformin might be safely and effectively repurposed to manage at least a subset of tinnitus patients while discussing the potential role of adenosine receptor agonists as potential future tinnitus therapeutics.}, } @article {pmid38293509, year = {2024}, author = {Hu, Y and Huang, D and Jiang, Y and Yu, Q and Lu, J and Ding, Y and Shi, Y}, title = {Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China.}, journal = {Heliyon}, volume = {10}, number = {2}, pages = {e24096}, pmid = {38293509}, issn = {2405-8440}, abstract = {BACKGROUND: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited.

OBJECTIVES: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies.

METHODS: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group.

RESULTS: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor.

CONCLUSIONS: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.}, } @article {pmid38293444, year = {2024}, author = {Lai, Z and Pu, T and Li, J and Bai, F and Wu, L and Tang, Y}, title = {Visual analysis of hotspots and trends in long COVID research based on bibliometric.}, journal = {Heliyon}, volume = {10}, number = {2}, pages = {e24053}, pmid = {38293444}, issn = {2405-8440}, abstract = {After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a series of symptoms may persist for a long time, which is now called long COVID. It was found that long COVID can affect all patients with COVID-19. Therefore, long COVID has become a hot topic. In this study, we used the WOS database as a sample data source to conduct a bibliometric and visual analysis of 1765 long COVID articles over the past three years through VOSviewer and R package. The results show that countries/authors in Europe and The United States of America contribute most of the articles, and their cooperation is also the most active. Keyword co-occurrence identified four clusters, with important topics including the mechanism, clinical symptoms, epidemiological characteristics, and management/treatment of long COVID. Themes such as "cognitive impairment", "endothelial dysfunction", "diagnosis", and "biomarkers" are likely to be the focus of new attention in the coming period. In addition, we put forward the possible research opportunities on long COVID for researchers and practitioners to facilitate future research.}, } @article {pmid38288178, year = {2023}, author = {Eastin, EF and Tiwari, A and Quach, TC and Bonilla, HF and Miglis, MG and Yang, PC and Geng, LN}, title = {New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51286}, pmid = {38288178}, issn = {2168-8184}, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity. Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.}, } @article {pmid38288123, year = {2023}, author = {Zhang, J and Xia, Y and Li, X and He, R and Xie, X}, title = {Case report: A case of Acute Macular Neuroretinopathy secondary to Influenza A virus during Long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1302504}, pmid = {38288123}, issn = {1664-3224}, mesh = {Humans ; Female ; SARS-CoV-2 ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Influenza A virus ; *Virus Diseases ; *White Dot Syndromes ; }, abstract = {Ocular abnormalities have been reported in association with viral infections, including Long COVID, a debilitating illness caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This report presents a case of a female patient diagnosed with Acute Macular Neuroretinopathy (AMN) following an Influenza A virus infection during Long COVID who experienced severe inflammation symptoms and ocular complications. We hypothesize that the rare occurrence of AMN in this patient could be associated with the immune storm secondary to the viral infection during Long COVID.}, } @article {pmid38287540, year = {2024}, author = {Yin, H and Li, Y and Qian, J and Lu, L}, title = {Bier spots associated with long COVID.}, journal = {International journal of rheumatic diseases}, volume = {27}, number = {1}, pages = {e15042}, doi = {10.1111/1756-185X.15042}, pmid = {38287540}, issn = {1756-185X}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Skin ; *Hypopigmentation ; }, } @article {pmid38287466, year = {2024}, author = {Buonsenso, D and Camporesi, A and Morello, R and De Rose, C and Fracasso, M and Valentini, P}, title = {Paediatric long COVID studies should focus on clinical evaluations that examine the impact on daily life not just self-reported symptoms.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {113}, number = {4}, pages = {778-780}, doi = {10.1111/apa.17129}, pmid = {38287466}, issn = {1651-2227}, support = {65925795//Pfizer/ ; }, mesh = {Humans ; Child ; *Post-Acute COVID-19 Syndrome ; Self Report ; *COVID-19 ; Quality of Life ; }, } @article {pmid38287294, year = {2024}, author = {Soare, IA and Ansari, W and Nguyen, JL and Mendes, D and Ahmed, W and Atkinson, J and Scott, A and Atwell, JE and Longworth, L and Becker, F}, title = {Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection.}, journal = {Health and quality of life outcomes}, volume = {22}, number = {1}, pages = {12}, pmid = {38287294}, issn = {1477-7525}, mesh = {Adult ; Adolescent ; Humans ; *Quality of Life ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19 ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Health Status ; }, abstract = {BACKGROUND: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19.

METHODS: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL.

RESULTS: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (β=-0.080, p = 0.001) and long COVID (β=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (β=-0.147, p = 0.026) and long (β=-0.186, p < 0.001) COVID.

CONCLUSION: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.}, } @article {pmid38287232, year = {2024}, author = {Kosel, I and Aydin, G and Taşcilar Uyanik, LN}, title = {Functional evaluation of physical performance, gait, balance and activities of daily living in older individuals with long COVID syndrome.}, journal = {Australasian journal on ageing}, volume = {43}, number = {2}, pages = {343-350}, doi = {10.1111/ajag.13274}, pmid = {38287232}, issn = {1741-6612}, mesh = {Humans ; Female ; Aged ; *Activities of Daily Living ; Male ; *Postural Balance ; *COVID-19/physiopathology ; *Gait ; *Physical Functional Performance ; Geriatric Assessment ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Aged, 80 and over ; }, abstract = {OBJECTIVE: The aim of our study was to evaluate the physical performance, balance, gait and activities of daily living (ADL) of older individuals with long COVID syndrome (LCS).

METHODS: A total of 124 individuals (49% women) with a mean age of 71.8 ± 5.8 years were included in the study. Participants were divided into two groups, older individuals with LCS in the LCS group and older individuals who were not diagnosed with COVID-19 in the CON (control) group. Physical performance of participants was evaluated with the Alusti Test, balance and gait assessment was evaluated with the Tinetti Balance and Gait Assessment (TBGA), and ADL were evaluated with the Barthel Index (BI).

RESULTS: In the evaluations between groups, the mean score of active muscular mobility of right and left upper extremities, transfer supine position to sitting, trunk in sitting position and standing, which are among the subparameters of the Alusti Test, were statistically significantly lower in LCS compared to CON (p < .05). TBGA total score and gait section mean score of TBGA were statistically significantly lower in LCS than in CON (p < .05). There was no significant difference between the groups in the balance section of the TBGA and the mean BI scores (p > .05).

CONCLUSIONS: It was concluded that physical performance parameters related to active muscular mobility of the upper extremity, transfer supine position to sitting, trunk in sitting position and walking in LCS were negatively affected by the disease, but this did not affect the level of balance and independence in ADL.}, } @article {pmid38287186, year = {2024}, author = {Rasika, S and Nogueiras, R and Schwaninger, M and Prevot, V}, title = {Seeing through the fog: a neuroendocrine explanation for post-COVID cognitive deficits.}, journal = {Nature reviews. Endocrinology}, volume = {20}, number = {4}, pages = {189-190}, pmid = {38287186}, issn = {1759-5037}, support = {810331/ERC_/European Research Council/International ; }, mesh = {Humans ; Animals ; *COVID-19 ; *Cognitive Dysfunction/etiology ; Service Animals ; Cognition ; }, abstract = {Gonadotropin-releasing hormone is implicated in cognitive functions, and its loss is a factor in pathological brain ageing. There are similarities between these processes and the neurological and cognitive deficits observed in patients with long COVID. Here, we explore the hypothesis that neuroanatomical and transcriptomic alterations associated with long-COVID could stem from this neuroendocrine perturbation.}, } @article {pmid38287106, year = {2024}, author = {Brackel, CLH and Noij, LCE and Vijverberg, SJH and Legghe, CL and Maitland-van der Zee, AH and van Goudoever, JB and Buonsenso, D and Munblit, D and Sigfrid, L and McFarland, S and Anmyr, L and Ashkenazi-Hoffnung, L and Bellinat, APN and Dias, NLS and Edwards, A and Fashina, T and Juraški, RG and Gonçalves, ALN and Hansted, E and Herczeg, V and Hertting, O and Jankauskaite, LN and Kaswandani, N and Kevalas, R and Krivácsy, P and Lorenz, M and Malone, LA and McVoy, M and Miller, DW and Morrow, AK and Nugawela, MD and Oliveira, CR and Oliveira, PRS and Osmanov, IM and Overmars, IM and Paintsil, E and Pinto Pereira, SM and Prawira, Y and Putri, ND and Ramos, RCF and Rasche, M and Ryd-Rinder, M and De Rose, C and Samitova, E and Jovanović, TS and Say, D and Scott, JT and Shachar-Lavie, I and Shafran, R and Shmueli, E and Snipaitiene, A and Stephenson, T and Ténai, N and Tosif, S and Turkalj, M and Valentini, P and Vasconcelos, LRS and Villard, L and Vilser, D and Hashimoto, S and Terheggen-Lagro, SWJ}, title = {International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.}, journal = {Pediatric research}, volume = {96}, number = {2}, pages = {319-324}, pmid = {38287106}, issn = {1530-0447}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Child ; Cross-Sectional Studies ; Female ; Adolescent ; Male ; Child, Preschool ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Infant ; }, abstract = {BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care.

METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care.

RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support.

CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration.

IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.}, } @article {pmid38287094, year = {2024}, author = {Wilk, P and Stranges, S and Cuschieri, S}, title = {Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe.}, journal = {International journal of obesity (2005)}, volume = {48}, number = {6}, pages = {821-829}, pmid = {38287094}, issn = {1476-5497}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology ; *Body Mass Index ; Europe/epidemiology ; Middle Aged ; Aged ; Risk Factors ; Prospective Studies ; Sex Factors ; Longitudinal Studies ; SARS-CoV-2 ; Retirement/statistics & numerical data ; Obesity/epidemiology ; Health Surveys ; Aged, 80 and over ; }, abstract = {BACKGROUND: Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study.

METHODS: A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe's (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID.

RESULTS: Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents' place of residence.

CONCLUSION: Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.}, } @article {pmid38285646, year = {2024}, author = {McMaster, MW and Dey, S and Fishkin, T and Wang, A and Frishman, WH and Aronow, WS}, title = {The Impact of Long COVID-19 on the Cardiovascular System.}, journal = {Cardiology in review}, volume = {}, number = {}, pages = {}, doi = {10.1097/CRD.0000000000000654}, pmid = {38285646}, issn = {1538-4683}, abstract = {Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.}, } @article {pmid38284721, year = {2024}, author = {Ghoreshi, ZA and Abbasi-Jorjandi, M and Asadikaram, G and Sharif-Zak, M and Haddad, MK and Afgar, A and Arefinia, N and Dabiri, S and Rosen, C}, title = {Time Course of Biochemical and Metabolic Parameters During and After COVID-19.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673282210231220115719}, pmid = {38284721}, issn = {1875-533X}, abstract = {BACKGROUND: Long COVID is characterized by the persistence of symptoms among individuals who are infected with the SARS-CoV-2 virus. The enduring impact of these long-term effects on the health and well-being of those affected cannot be denied.

METHOD: About 470 patients with SARS-CoV-2 were consecutively recruited in this longitudinal study. The participants were entered into moderate, severe, and critical groups. 235 out of 470 participants were female. The levels of fasting blood sugar (FBS), alanine transaminase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphatase (ALP), creatinine (Cr), urea, uric acid (UA), and total protein (TP) were measured during hospitalization and again at one and three months after infection. The levels of Zn and hemoglobin A1c (HbA1c) were also measured only during hospitalization.

RESULT: COVID-19 severity was associated with high levels of glucose, urea, Cr, ALT, AST, ALP, and HbA1c, and low levels of Zn, UA, and TP. There were significant sex differences for these markers at all three-time points. Glucose, urea, Cr, ALT, AST, and ALP all decreased three months after infection, whereas the levels of UA and TP returned towards normal.

CONCLUSION: COVID-19 infection affects the levels of multiple biochemical factors in a gender-dependent manner. The biochemical changes become more tangible with increasing disease severity, and several of these predict mortality. Levels begin to return to normal after the acute phase of the disease, but in some individuals, at three months, several markers were still not within the normal range. Whether the trajectory of these changes can predict long COVID requires further testing.}, } @article {pmid38284464, year = {2024}, author = {Çulha, Y and Büyükyılmaz, F and Çulha, MG}, title = {The effect of long-term COVID-19 on aetiological factors related to nocturia.}, journal = {Journal of clinical nursing}, volume = {33}, number = {3}, pages = {1161-1168}, doi = {10.1111/jocn.17037}, pmid = {38284464}, issn = {1365-2702}, mesh = {Humans ; *Nocturia/etiology/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Urinary Bladder, Overactive/complications/drug therapy ; Urinary Bladder ; }, abstract = {AIMS AND OBJECTIVES: This study was conducted to examine the possible aetiology of nocturia in patients with long-term COVID-19.

BACKGROUND: Physical and neuropsychiatric symptoms, an increase in overactive bladder symptoms, especially from urinary system complaints, has been reported in patients with COVID-19, 10-14 weeks after the illness.

DESIGN: A descriptive design.

METHODS: The study consisted of 70 patients who had experienced COVID-19, had nocturia, and were followed in the State Hospital between April and July 2022. Data were collected using a patient information form, the 'TANGO' nocturia screening tool, and the Visual Analog Scale. This study was created in accordance with the STROBE Statement Checklist.

RESULTS: When the nocturia effects of long-term COVID-19 were examined it was determined that the urinary tract was the 'priority' aetiological condition. It was observed that there was a significant difference between the aetiological factor groups in terms of the mean age of the patients and the number of nocturia (p < .05). According to post-hoc analysis, the mean age of patients with a dominant cardio-metabolic factor was found to be significantly younger (p < .05). In addition, when comparing the number of nocturia according to the aetiological factors of the patients, it was observed that the number of nocturia was significantly frequent in the patients with a dominant sleep factor (p < .05).

CONCLUSIONS: It was found that the urinary tract aetiological factor was dominant in patients with long-term COVID-19 and nocturia, patients with a dominant cardiovascular aetiological factor were younger, and that the number of nocturia was higher in patients with a dominant sleep factor.

Identification of the early signs and symptoms and underlying causes of nocturia in individuals with post-COVID-19 syndrome will enable nurses and health professionals to guide the early identification of different underlying problems, as well as the implementation of approaches to treat and eliminate nocturia.

The patients contributed to the study by agreeing to participate in the evaluation of nocturia complaints after COVID-19 infection.}, } @article {pmid38283209, year = {2023}, author = {Al Jahdhami, I and Arshad, H and Omar, H and Bennji, SM and Al Nomani, K and Al Ghafri, M and Al Syabi, M and Al Hinai, S and Al Mawali, A}, title = {Persistence of Symptoms Following Hospitalization for COVID-19 in Oman: A Bidirectional Observational Study.}, journal = {Oman medical journal}, volume = {38}, number = {6}, pages = {e570}, pmid = {38283209}, issn = {1999-768X}, abstract = {OBJECTIVES: This study sought to assess the prevalence of persistent COVID-19-related symptoms in patients with mild, severe, and critical disease.

METHODS: We conducted a bidirectional cohort observational study that included all adult patients ≥ 18 years, admitted to Armed Forces Hospital, Muscat between July 2020 and June 2022, with COVID-19 infection and discharged alive. Patients were requested to attend outpatient clinic at weeks six and 12 post-discharge, where they filled out a questionnaire and underwent a chest X-ray. Additionally, blood tests were performed if necessary. Healthcare workers with mild infections were also requested to fill out a questionnaire about their initial symptoms, persistent symptoms, and comorbidities.

RESULTS: The study included 468 patients, comprising 261 hospitalized patients and 207 healthcare workers. On follow-up, 39.7% of patients presented with residual symptoms, such as cough, breathlessness, and joint pain. These symptoms were more common in patients with medical comorbidities, particularly hypertension, diabetes, and dyslipidemia. Notably, these symptoms were also observed in patients with mild disease. Post-COVID-19 pulmonary fibrosis was observed in 21 patients, mainly among those admitted to the intensive care unit or requiring prolonged hospitalization.

CONCLUSIONS: This study highlights the persistence of symptoms and the prevalence of post-COVID-19 syndrome at two months post-discharge, especially among patients with severe and critical disease during the acute phase. Various predictors of post-COVID-19 syndrome were identified, including female gender, older age, presence of comorbidities, disease severity, and hypertension. Therefore, patients in these categories require thorough evaluation and long-term follow-up to manage residual symptoms.}, } @article {pmid38282368, year = {2024}, author = {McGarrigle, WJ and Furst, J and Jason, LA}, title = {Psychometric evaluation of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) among adults with Long COVID, ME/CFS, and healthy controls: A machine learning approach.}, journal = {Journal of health psychology}, volume = {29}, number = {11}, pages = {1241-1252}, doi = {10.1177/13591053231223882}, pmid = {38282368}, issn = {1461-7277}, mesh = {Humans ; *Machine Learning ; *Psychometrics/instrumentation ; *COVID-19/psychology/diagnosis ; Male ; Female ; Adult ; Middle Aged ; Surveys and Questionnaires/standards ; *Fatigue Syndrome, Chronic/diagnosis/psychology ; Post-Acute COVID-19 Syndrome ; Sensitivity and Specificity ; Aged ; SARS-CoV-2 ; }, abstract = {Long COVID shares a number of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including post-exertional malaise, severe fatigue, and neurocognitive deficits. Utilizing validated assessment tools that accurately and efficiently screen for these conditions can facilitate diagnostic and treatment efforts, thereby improving patient outcomes. In this study, we generated a series of random forest machine learning algorithms to evaluate the psychometric properties of the DePaul Symptom Questionnaire-Short Form (DSQ-SF) in classifying large groups of adults with Long COVID, ME/CFS (without Long COVID), and healthy controls. We demonstrated that the DSQ-SF can accurately classify these populations with high degrees of sensitivity and specificity. In turn, we identified the particular DSQ-SF symptom items that best distinguish Long COVID from ME/CFS, as well as those that differentiate these illness groups from healthy controls.}, } @article {pmid38279329, year = {2024}, author = {Álvarez-Santacruz, C and Tyrkalska, SD and Candel, S}, title = {The Microbiota in Long COVID.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38279329}, issn = {1422-0067}, support = {00006/COVI/20//Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia/ ; 21118/SF/19//Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia/ ; Juan de la Cierva-Incorporación//Ministerio de Ciencia e Innovación/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Dysbiosis ; *Microbiota ; *Vaccines ; }, abstract = {Interest in the coronavirus disease 2019 (COVID-19) has progressively decreased lately, mainly due to the great effectivity of vaccines. Furthermore, no new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants able to circumvent the protection of these vaccines, while presenting high transmissibility and/or lethality, have appeared. However, long COVID has emerged as a huge threat to human health and economy globally. The human microbiota plays an important role in health and disease, participating in the modulation of innate and adaptive immune responses. Thus, multiple studies have found that the nasopharyngeal microbiota is altered in COVID-19 patients, with these changes associated with the onset and/or severity of the disease. Nevertheless, although dysbiosis has also been reported in long COVID patients, mainly in the gut, little is known about the possible involvement of the microbiota in the development of this disease. Therefore, in this work, we aim to fill this gap in the knowledge by discussing and comparing the most relevant studies that have been published in this field up to this point. Hence, we discuss that the relevance of long COVID has probably been underestimated, and that the available data suggest that the microbiota could be playing a pivotal role on the pathogenesis of the disease. Further research to elucidate the involvement of the microbiota in long COVID will be essential to explore new therapeutic strategies based on manipulation of the microbiota.}, } @article {pmid38279014, year = {2024}, author = {Toepfner, N and Brinkmann, F and Augustin, S and Stojanov, S and Behrends, U}, title = {Long COVID in pediatrics-epidemiology, diagnosis, and management.}, journal = {European journal of pediatrics}, volume = {183}, number = {4}, pages = {1543-1553}, pmid = {38279014}, issn = {1432-1076}, mesh = {Adolescent ; Humans ; Child ; Infant, Newborn ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic ; *COVID-19/diagnosis/epidemiology/therapy ; Quality of Life ; SARS-CoV-2 ; Disease Progression ; COVID-19 Testing ; }, abstract = {This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID - at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies. Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions. What is Known: • Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) - also termed Long COVID - in children and adolescents can lead to activity limitation and reduced quality of life. • PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available. What is New: • In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities. PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). • Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.}, } @article {pmid38278934, year = {2024}, author = {Ledford, H and Thompson, B}, title = {Audio long read: Long COVID is a double curse in low-income nations - here's why.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-024-00224-3}, pmid = {38278934}, issn = {1476-4687}, } @article {pmid38278908, year = {2024}, author = {Patel, D and Louca, C and Machuca Vargas, C}, title = {Oral manifestations of long COVID and the views of healthcare professionals.}, journal = {British dental journal}, volume = {236}, number = {2}, pages = {111-116}, pmid = {38278908}, issn = {1476-5373}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Qualitative Research ; Health Personnel ; Attitude of Health Personnel ; }, abstract = {Introduction Oral manifestations have been observed with this condition; however, little is known about their impact on the healthcare professionals routinely managing these patients.Aims To investigate the prevalence of the oral manifestations of long COVID and the healthcare professionals' views, experiences and practices for managing these conditions.Materials and methods A cross-sectional mixed-methods study, including a self-reported online questionnaire (n = 104) and healthcare professionals' (n = 7) semi-structured interviews, was conducted. Descriptive statistics and reflexive thematic analysis were used to analyse the data.Results In total, 78% of respondents reported one or more oral conditions associated with COVID-19. Changes in the sense of taste and/or smell (58%), dry mouth (48.1%) and mouth sores (45.7%) were frequently reported. Themes identified from healthcare professionals' interviews were areas for research, management and interdisciplinary collaboration.Discussion Allied healthcare professionals may assist dental professionals with managing oral manifestations of long COVID. Inadequate access to NHS dentistry is deterring patients worried about their oral symptoms and the limited oral knowledge of healthcare professionals affects their ability to manage patients.Conclusion Healthcare professionals have observed oral manifestations in individuals diagnosed with long COVID; however, further information and training on this topic would assist them with managing patients and increasing awareness among clinicians.}, } @article {pmid38278434, year = {2024}, author = {Nguyen, T and Zuin, M and Ngo, K and Gibson, CM}, title = {Myocardial Infarction During SARS-CoV-2 Infection: Another Piece in the Long-COVID Puzzle.}, journal = {The American journal of cardiology}, volume = {215}, number = {}, pages = {92-93}, doi = {10.1016/j.amjcard.2024.01.013}, pmid = {38278434}, issn = {1879-1913}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Myocardial Infarction/epidemiology ; }, } @article {pmid38277895, year = {2024}, author = {Schurr, M and Junne, F and Martus, P and Paul, G and Jürgensen, JS and Allwang, C and Binneböse, M and Wallis, H and Mikolajczyk, R and Galante-Gottschalk, A and Zipfel, S and Ehehalt, S and Giel, KE}, title = {SARS-CoV-2 infection is associated with physical but not mental fatigue - Findings from a longitudinal controlled population-based study.}, journal = {Journal of psychosomatic research}, volume = {178}, number = {}, pages = {111598}, doi = {10.1016/j.jpsychores.2024.111598}, pmid = {38277895}, issn = {1879-1360}, mesh = {Adult ; Humans ; Middle Aged ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; SARS-CoV-2 ; Anxiety/epidemiology ; Mental Fatigue/epidemiology ; Depression/epidemiology ; }, abstract = {OBJECTIVE: Fatigue has been identified as the core symptom of long-Covid, however, putative pandemic-related influences remain largely unclear. We investigated trajectories of total, physical and mental fatigue and the factors associated with it in previously infected and non-infected individuals up to one year post- infection.

METHODS: We used data from a longitudinal cohort study of German adults with two samples: A representative probability sample and a sample of individuals with proven SARS-CoV-2 infection. Surveys were conducted in spring 2020(T1), autumn 2020(T2) and summer 2021(T3). Fatigue was assessed using the FAS, distinguishes between physical and mental fatigue. Depression, anxiety and stress were assessed using PHQ-4 and PSQ.

RESULTS: 1990 participants [mean age 47.2 (SD = 17.0), 30.5% previously infected] were included in the survey at T1 (n = 1118 at T2, n = 692 at T3). Total and physical fatigue, but not mental fatigue were significantly higher in the previously infected compared to the non-infected sample at T2, but this group difference disappeared at T3. We identified Covid-infection as a factor associated with transient total and physical fatigue at T2. Depression, anxiety and stress at T1 were associated with total, physical and mental fatigue at both follow-ups.

CONCLUSIONS: Our results highlight the importance of considering physical and mental fatigue as separate entities, while suggesting a greater relevance of the physical signs of fatigue in understanding long-Covid. The results further showed that baseline mental health symptoms were the most strongly associated with fatigue trajectories.}, } @article {pmid38277734, year = {2024}, author = {Suárez, D and Pascual, E and Soravilla, JR}, title = {[Long covid and disability].}, journal = {Semergen}, volume = {50}, number = {2}, pages = {102189}, doi = {10.1016/j.semerg.2023.102189}, pmid = {38277734}, issn = {1578-8865}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Anxiety ; Pandemics ; }, abstract = {Long covid is a health problem that will entail a high hidden cost attributable to the pandemic years after it because it affects the work capacity of many workers. Given the millions of covid-19 cases worldwide and current research showing that one in 7covid-19 patients remain symptomatic at 12 weeks, the number of long covid patients is likely to be substantial. Long covid is characterized by heterogeneous sequelae that often affect multiple systems, organs with an impact on the functioning and capacity of the worker. Workers with long covid symptoms can return to their occupation but this involves a complex individualized approach to the impact of symptoms on work, adjustments and modifications to the workplace. Patients with long covid typically report prolonged multisystem involvement and signicant disability. The psychological cost to the worker must also be addressed. A survey by the Community of Madrid (CCOO, SATSE, CSIF, AMYTS) in 2022 reveals that 24.5% of those affected by long covid were sick for more than 12 months; 30% of those affected by persistent covid need and adaption to their workplace. In Spain, more than 10million people infected with SARS-CoV-2 have been reported since the pandemic began, so it is estimated that there could be one million people with persistent covid. In 2021 alone there were more than 2.6 million sick leave due to covid-19 in Spain, the average duration of which was 10 days. One hundred million people around the world suffer from persistent covid, but few countries officially count them, nor do they help those affected with employment. In advanced countries, like the United States, long covid is treated as a disability,and the number of people with disabilities working or looking for work increased by 1.36 million, an increase of 23%, between January 2021 and January 2022. In the United Kingdom, some 200,000 people are not working or are not looking for work due to long-term health problems attributable to long covid, since the pandemic began.}, } @article {pmid38277732, year = {2024}, author = {Gamero-de-Luna, EJ and Sánchez-Jaén, MR}, title = {[Genetic factors associated with long COVID].}, journal = {Semergen}, volume = {50}, number = {2}, pages = {102187}, doi = {10.1016/j.semerg.2023.102187}, pmid = {38277732}, issn = {1578-8865}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Forkhead Transcription Factors ; }, abstract = {INTRODUCTION: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID.

MATERIAL AND METHODS: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review.

RESULTS: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus.

CONCLUSIONS: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.}, } @article {pmid38277361, year = {2024}, author = {Obeidat, M and Abu Zahra, A and Alsattari, F}, title = {Prevalence and characteristics of long COVID-19 in Jordan: A cross sectional survey.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0295969}, pmid = {38277361}, issn = {1932-6203}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Cross-Sectional Studies ; Jordan/epidemiology ; Prevalence ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chronic Disease ; Vitamin D ; }, abstract = {Early in the pandemic, the spread of the emerging virus SARS-CoV-2 was causing mild illness lasting less than two weeks for most people, with a small proportion of people developing serious illness or death. However, as the pandemic progressed, many people reported suffering from symptoms for weeks or months after their initial infection. Persistence of COVID-19 symptoms beyond one month, or what is known as long COVID-19, is recognized as a risk of acute infection. Up to date, information on long COVID-19 among Jordanian patients has not been reported. Therefore, we sought to conduct this cross-sectional study utilizing a self-administered survey. The survey asks a series of questions regarding participant demographics, long COVID-19 symptoms, information about pre-existing medical history, supplements, vaccination history, and symptoms recorded after vaccination. Chi square analysis was conducted on 990 responders, and the results showed a significant correlation (P<0.05) between long COVID-19 syndrome and age, obesity, chronic illness, vitamin D intake, number of times infected by COVID-19, number of COVID-19 symptoms and whether the infection was pre or post vaccination. The long-term symptoms most enriched in those with long COVID-19 were tinnitus (73.4%), concentration problems (68.6%) and muscle and joint ache (68.3%).A binomial logistic regression analysis was done to explore the predictors of long COVID-19 and found that age 18-45, marital status, vitamin D, number of COVID-19 symptoms and signs after vaccination are positive predictors of long COVID-19, while zinc intake is a negative predictor. Although further studies on long-term persistence of symptoms are needed, the present study provides a baseline that allows us to understand the frequency and nature of long COVID-19 among Jordanians.}, } @article {pmid38277026, year = {2024}, author = {D'Ávila, LBO and Milani, M and Le Bihan, DCS and de Lima, ACGB and Milani, JGPO and Cipriano, GFB and da Silva, VZM and Cipriano, G}, title = {Longitudinal strain and myocardial work in symptomatic patients having recovered from COVID-19 and possible associations with the severity of the disease.}, journal = {The international journal of cardiovascular imaging}, volume = {40}, number = {4}, pages = {745-756}, pmid = {38277026}, issn = {1875-8312}, mesh = {Humans ; *COVID-19/complications/diagnosis/physiopathology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Cross-Sectional Studies ; *Severity of Illness Index ; Adult ; Echocardiography ; Ventricular Function, Left ; SARS-CoV-2 ; Oxygen Consumption ; Ventricular Dysfunction, Left/physiopathology/diagnostic imaging ; Exercise Test ; }, abstract = {COVID-19 may have residual consequences in multiple organs, including the cardiovascular system. The purpose of the present investigation is to quantify myocardial function in symptomatic individuals with long COVID and investigate the association between illness severity and myocardial function. A retrospective cross-sectional study was conducted in which symptomatic individuals with previous COVID-19 underwent echocardiographic analysis of left ventricle global longitudinal strain (LVGLS) and myocardial work (MW). Individuals also performed cardiopulmonary testing (CPX) to assess peak oxygen uptake (VO2peak). Differences between illness severity subgroups were analyzed by the Mann-Whitney test. Correlations were calculated using the Spearman correlation test. Multilinear regressions were performed to evaluate the influences of COVID-19 severity, body mass index, age, and sex on MW. Fifty-six individuals were included (critical subgroup: 17; moderate/severe subgroup: 39), 59% females; median age: 56 years (IQR: 43-63). CPX revealed a substantial reduction in VO2peak (median of 53% of predicted values). LVGLS were not statistically different between subgroups. Global wasted work (GWW) was higher in the critical subgroup [146 (104-212) versus 121 (74-163) mmHg%, p = 0.01], and global work efficiency (GWE) was lower in this subgroup [93 (91-95) versus 94 (93-96), p = 0.03]. Illness severity was the only independent predictor of GWW and GWE (GWW: r[2] = 0.167; p = 0.009; GWE: r[2] = 0.172; p = 0.005) in multilinear regressions. In our study with long COVID-19 individuals, despite having a similar LVGLS, patients had subclinical LV dysfunction, demonstrated only by an increase in GWW and a decrease in GWE.}, } @article {pmid38275749, year = {2023}, author = {León-Moreno, LC and Reza-Zaldívar, EE and Hernández-Sapiéns, MA and Villafaña-Estarrón, E and García-Martin, M and Ojeda-Hernández, DD and Matias-Guiu, JA and Gomez-Pinedo, U and Matias-Guiu, J and Canales-Aguirre, AA}, title = {Mesenchymal Stem Cell-Based Therapies in the Post-Acute Neurological COVID Syndrome: Current Landscape and Opportunities.}, journal = {Biomolecules}, volume = {14}, number = {1}, pages = {}, pmid = {38275749}, issn = {2218-273X}, support = {9790-2021.//Fondo de Desarrollo Científico de Jalisco/ ; }, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mesenchymal Stem Cells/physiology ; Central Nervous System ; }, abstract = {One of the main concerns related to SARS-CoV-2 infection is the symptoms that could be developed by survivors, known as long COVID, a syndrome characterized by persistent symptoms beyond the acute phase of the infection. This syndrome has emerged as a complex and debilitating condition with a diverse range of manifestations affecting multiple organ systems. It is increasingly recognized for affecting the Central Nervous System, in which one of the most prevalent manifestations is cognitive impairment. The search for effective therapeutic interventions has led to growing interest in Mesenchymal Stem Cell (MSC)-based therapies due to their immunomodulatory, anti-inflammatory, and tissue regenerative properties. This review provides a comprehensive analysis of the current understanding and potential applications of MSC-based interventions in the context of post-acute neurological COVID-19 syndrome, exploring the underlying mechanisms by which MSCs exert their effects on neuroinflammation, neuroprotection, and neural tissue repair. Moreover, we discuss the challenges and considerations specific to employing MSC-based therapies, including optimal delivery methods, and functional treatment enhancements.}, } @article {pmid38274511, year = {2023}, author = {Martínez-Borba, V and Martínez-García, L and Peris-Baquero, Ó and Osma, J and Del Corral-Beamonte, E}, title = {Guiding future research on psychological interventions in people with COVID-19 and post COVID syndrome and comorbid emotional disorders based on a systematic review.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1305463}, pmid = {38274511}, issn = {2296-2565}, mesh = {Adult ; Humans ; Psychosocial Intervention ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/epidemiology ; *Cognitive Behavioral Therapy/methods ; }, abstract = {OBJECTIVE: The COVID-19 pandemic has been emotionally challenging for the entire population and especially for people who contracted the illness. This systematic review summarizes psychological interventions implemented in COVID-19 and long COVID-19 patients who presented comorbid emotional disorders.

METHODS AND MEASURES: 3,839 articles were identified in 6 databases and 43 of them were included in this work. Two independent researchers selected the articles and assessed their quality.

RESULTS: 2,359 adults were included in this review. Severity of COVID-19 symptoms ranged from asymptomatic to hospitalized patients; only 3 studies included long COVID-19 populations. Similar number of randomized controlled studies (n = 15) and case studies (n = 14) were found. Emotional disorders were anxiety and/or depressive symptoms (n = 39) and the psychological intervention most represented had a cognitive behavioral approach (n = 10). Length of psychological programs ranged from 1-5 sessions (n = 6) to 16 appointments (n = 2). Some programs were distributed on a daily (n = 4) or weekly basis (n = 2), but other proposed several sessions a week (n = 4). Short (5-10 min, n = 4) and long sessions (60-90 min, n = 3) are proposed. Most interventions were supported by the use of technologies (n = 18). Important risk of bias was present in several studies.

CONCLUSION: Promising results in the reduction of depressive, anxiety and related disorders have been found. However, important limitations in current psychological interventions were detected (i.e., duration, format, length, and efficacy of interventions were not consistently established across investigations). The results derived from our work may help to understand clinical practices in the context of pandemics and could guide future efforts to manage emotional suffering in COVID-19 patients. A stepped model of care could help to determine the dosage, length and format of delivery for each patient.Systematic review registration: PROSPERO 2022 CRD42022367227. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022367227.}, } @article {pmid38274344, year = {2024}, author = {Georgakopoulou, VE and Makrodimitri, S and Gkoufa, A and Apostolidi, E and Provatas, S and Papalexis, P and Spandidos, DA and Lempesis, IG and Gamaletsou, MN and Sipsas, NV}, title = {Lung function at three months after hospitalization due to COVID‑19 pneumonia: Comparison of alpha, delta and omicron variant predominance periods.}, journal = {Experimental and therapeutic medicine}, volume = {27}, number = {2}, pages = {83}, pmid = {38274344}, issn = {1792-1015}, abstract = {The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant.}, } @article {pmid38274115, year = {2024}, author = {Muñoz-Chápuli Gutiérrez, M and Prat, AS and Vila, AD and Claverol, MB and Martínez, PP and Recarte, PP and Benéitez, MV and García, CA and Muñoz, EC and Navarro, M and Navarro, PG and Álvarez-Mon, M and Ortega, MA and de León-Luís, J}, title = {Post-COVID-19 condition in pregnant and postpartum women: a long-term follow-up, observational prospective study.}, journal = {EClinicalMedicine}, volume = {67}, number = {}, pages = {102398}, pmid = {38274115}, issn = {2589-5370}, abstract = {BACKGROUND: Post-COVID-19 condition has recently been defined as new or persistent common COVID-19 symptoms occurring three months after disease onset. The pathology of the disease is unclear, but immune and vascular factors seem to play a significant role. The incidence, severity, and implications of the disease after COVID-19 infection in pregnancy have not been established. We aimed to study the incidence and main risk factors for post-COVID-19 condition in an obstetric population and their implications for maternal and perinatal morbimortality.

METHODS: This is a prospective observational cohort study undertaken including women during pregnancy or at admission for labour with acute COVID-19 infection from March 9th, 2020 to June 11th, 2022. The inclusion criteria were confirmed acute COVID-19 infection during the recruitment period, a lack of significant language barrier and consent for follow-up. Patients were clinically followed-up by telephone via semi structured questionnaires. The exclusion criteria were loss to follow-up, spontaneous miscarriage, and legal termination of pregnancy. Patients were classified into groups according to the severity of symptoms at onset. We included patients from the first six first waves of the pandemic according to national epidemiological data in Spain. We studied the incidence of post-COVID-19 condition and their main demographic, clinical and obstetric risk factors.

FINDINGS: A total of 409 pregnant women were recruited at acute diagnosis, and 286 were followed-up. The mean time to follow-up was 92 weeks (standard deviation ± 28 weeks; median 100 weeks (Interquartile range: 76; 112)). A total of 140 patients had at least one post-COVID-19 symptom at least three months after acute infection. Neurological (60%) and cutaneous (55%) manifestations were the most frequent findings. The following profiles were identified as presenting a higher risk of post-COVID-19 condition: migrant women born in countries with lower Human Development Index; multiparous women; women with COVID-19 during pregnancy, mainly during the first and third trimesters, and in the first and second waves of the pandemic; women who had a higher number of symptoms; women who had a higher incidence of moderate and severe symptoms; women who required hospitalisation due to COVID-19 complications; and women who were not vaccinated before disease onset. We did not find any significant difference in perinatal results, such as gestational week at delivery, birthweight, the need for neonatal care or 5-min Apgar score, and newborns benefited from a high rate of breastfeeding at discharge. Women who were infected during successive waves of the pandemic had a significant and constant decrease in the risk of post-COVID-19 condition comparing to estimated risk in the first wave (OR: 0.70; 95% CI: 0.62, 0.92). Symptoms tended to resolve over time heterogeneously. Symptoms of myalgia and arthralgia took longer to resolve (mean of 60 weeks and 54 weeks, respectively). In a small but significant proportion of patients, neurological and psycho-emotional symptoms tended to become chronic after 90 weeks.

INTERPRETATION: At least 34.2% of obstetric patients from our cohort with acute COVID-19 infection presented post-COVID-19 condition symptoms. Demographic and acute disease characteristics as well as specific pregnancy-related risk factors were identified. This is the first study to assess post-COVID-19 condition in pregnant women. Further analysis on the biological pathophysiology of post-COVID-19 is needed to explain the characteristics of the disease.

FUNDING: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/01244" and co-funded by the European Union, as well as P2022/BMD-7321 (Comunidad de Madrid) and ProACapital, Halekulani S.L. and MJR.}, } @article {pmid38274052, year = {2023}, author = {Ahmad, I and Amelio, A and Merla, A and Scozzari, F}, title = {A survey on the role of artificial intelligence in managing Long COVID.}, journal = {Frontiers in artificial intelligence}, volume = {6}, number = {}, pages = {1292466}, pmid = {38274052}, issn = {2624-8212}, abstract = {In the last years, several techniques of artificial intelligence have been applied to data from COVID-19. In addition to the symptoms related to COVID-19, many individuals with SARS-CoV-2 infection have described various long-lasting symptoms, now termed Long COVID. In this context, artificial intelligence techniques have been utilized to analyze data from Long COVID patients in order to assist doctors and alleviate the considerable strain on care and rehabilitation facilities. In this paper, we explore the impact of the machine learning methodologies that have been applied to analyze the many aspects of Long COVID syndrome, from clinical presentation through diagnosis. We also include the text mining techniques used to extract insights and trends from large amounts of text data related to Long COVID. Finally, we critically compare the various approaches and outline the work that has to be done to create a robust artificial intelligence approach for efficient diagnosis and treatment of Long COVID.}, } @article {pmid38273933, year = {2024}, author = {Bellone, S and Siegel, ER and Scheim, DE and Santin, AD}, title = {Increased von Willebrand and Factor VIII plasma levels in gynecologic patients with Post-Acute-COVID-Sequela (PASC)/Long COVID.}, journal = {Gynecologic oncology reports}, volume = {51}, number = {}, pages = {101324}, pmid = {38273933}, issn = {2352-5789}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {Up to 30 % of COVID-infected patients may develop post-acute sequelae of COVID-19 (PASC), also known as Long COVID (LC), a syndrome characterized by a variety of debilitating symptoms lasting for more than 3 months after the acute infection. While the pathophysiological mechanisms behind PASC/LC are not completely understood, growing evidence suggests that an important component of this syndrome may be related to persistent microvascular inflammation causing clumping/clotting of red blood cells and platelets and thrombotic complications. We retrospectively evaluated the plasma levels of von Willebrand factor (VWF), Factor VIII and D-dimer in 10 gynecologic patients (60 % with an endometrial or ovarian cancer diagnosis) affected by PASC/LC vs 5 control patients (60 % harboring endometrial or ovarian tumors). We found elevated VWF and Factor VIII levels in all 10 PASC/LC patients (means of 254 % and 229 %, respectively) vs none of the 5 randomly selected cancer control patients (means of 108 % and 95 %, respectively), p = 0.0046 and p < 0.0001, respectively. In contrast, no significant difference was noted in the levels of D-dimer in PASC/LC. Importantly, abnormally elevated VWF and Factor VIII levels were found to persist for at least 2 years in patients with Long COVID symptoms. VWF and Factor VIII but not D-dimer levels are significantly elevated in the plasma of PASC/LC cancer patients. Abnormally and persistently elevated VWF and Factor VIII levels may represent the results of persistent microvascular damage (i.e., spike-induced endotheliosis) and may be biomarkers of persistent inflammation in gynecologic patients with PASC/LC.}, } @article {pmid38272997, year = {2024}, author = {Klírová, M and Adamová, A and Biačková, N and Laskov, O and Renková, V and Stuchlíková, Z and Odnohová, K and Novák, T}, title = {Transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric symptoms of long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2193}, pmid = {38272997}, issn = {2045-2322}, support = {NU22-D-133//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; }, mesh = {Humans ; *Transcranial Direct Current Stimulation ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/therapy ; SARS-CoV-2 ; Prefrontal Cortex/physiology ; Double-Blind Method ; Treatment Outcome ; }, abstract = {The study aimed to assess the efficacy of transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric (NP) symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC), known as the long COVID. A double-blind, randomized, sham-controlled study compared the efficacy and safety of prefrontal cortex active tDCS to sham-tDCS in treating NP-PASC. Patients diagnosed with NP-PASC, with a Fatigue Impact Scale (FIS) score ≥ 40, were eligible for the study. Twenty tDCS sessions were administered within four weeks, with continuous, end-of-treatment, and follow-up measurements. The primary outcome was a change in the FIS at the end-of-treatment, analyzed in the intention-to-treat population. Data from 33 patients assigned to active (n = 16) or sham-tDCS (n = 17) were analyzed. After the treatment, a decrease in the FIS score was more pronounced in the sham than in the active group, yet the intergroup difference was insignificant (11.7 [95% CI -11.1 to 34.5], p = 0.6). Furthermore, no significant intergroup differences were observed regarding anxiety, depression, quality of life, and cognitive performance. The small cohort sample, differences in baseline FIS scores between groups (non-stratified randomization), or chosen stimulation parameters may have influenced our findings. However, it might also be possible that the expected mechanism of action of tDCS is insufficient to treat these conditions.}, } @article {pmid38272788, year = {2024}, author = {Lemogne, C and Gouraud, C and Ouazana Vedrines, C and Pritschkat, C and Rotenberg, L and Horn, M and Cathébras, P and Kachaner, A and Scherlinger, M and de Broucker, T and Pignon, B and Chauvet-Gelinier, JC and Günther, S and Gocko, X and Pitron, V and Ranque, B}, title = {National committee statement as a missed opportunity to acknowledge the relevance of a biopsychosocial approach in understanding long COVID.}, journal = {Journal of psychosomatic research}, volume = {186}, number = {}, pages = {111596}, doi = {10.1016/j.jpsychores.2024.111596}, pmid = {38272788}, issn = {1879-1360}, mesh = {Humans ; *COVID-19/psychology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Models, Biopsychosocial ; }, } @article {pmid38272505, year = {2024}, author = {Waters, A}, title = {Covid-19: Doctors instruct law firm in bid for compensation after developing long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {384}, number = {}, pages = {q188}, doi = {10.1136/bmj.q188}, pmid = {38272505}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Physicians ; }, } @article {pmid38270210, year = {2024}, author = {Sakurada, Y and Matsuda, Y and Motohashi, K and Hasegawa, T and Otsuka, Y and Nakano, Y and Tokumasu, K and Yamamoto, K and Sunada, N and Honda, H and Hagiya, H and Ueda, K and Otsuka, F}, title = {Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic.}, journal = {Journal of psychosomatic obstetrics and gynaecology}, volume = {45}, number = {1}, pages = {2305899}, doi = {10.1080/0167482X.2024.2305899}, pmid = {38270210}, issn = {1743-8942}, mesh = {Humans ; Female ; Retrospective Studies ; *COVID-19 ; Japan/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Ambulatory Care Facilities ; Fatigue ; Menstruation Disturbances/epidemiology ; }, abstract = {PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated.

METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances.

RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints.

CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.}, } @article {pmid38269448, year = {2024}, author = {Macleod-Hall, CI and Munafò, MR and Dyer, ML}, title = {Confirmation of COVID-19 infection status and reporting of Long COVID symptoms in a population-based birth cohort: No evidence of a nocebo effect.}, journal = {Journal of health psychology}, volume = {29}, number = {6}, pages = {581-594}, pmid = {38269448}, issn = {1461-7277}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_UU_00032/7/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/psychology ; Female ; Male ; Longitudinal Studies ; *Anxiety/psychology ; *Nocebo Effect ; Post-Acute COVID-19 Syndrome ; Birth Cohort ; Adult ; SARS-CoV-2 ; Surveys and Questionnaires ; Adolescent ; }, abstract = {Some patients with COVID-19 develop symptoms after the acute infection, known as 'Long COVID'. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort. We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test vs unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators. There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.}, } @article {pmid38269219, year = {2023}, author = {Schaefer, J and Khanna, D}, title = {Nutritional and Wellness Strategies for Neurological and Psychiatric Recovery From Post-COVID Syndrome and Post-acute Sequelae of COVID-19.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51076}, pmid = {38269219}, issn = {2168-8184}, abstract = {The post-COVID syndrome was officially recognized as a disability under the Americans with Disabilities Act, indicating that this syndrome has made a significant impact on our populace. Also, post-acute sequelae of COVID-19 (PASC) is a term that describes the long-term health problems that some people experience after being infected with the virus that causes COVID-19. These problems can last for weeks, months, or even years, and can affect various parts of the body, such as the heart, lungs, brain, and blood vessels. This narrative review paper utilized the PubMed database to explore the pathophysiology of post-COVID syndrome's neurological and psychiatric symptoms and PASC and make therapeutic connections to the known mechanisms of various nutritional, supplemental, and wellness approaches. Searches were queried on the PubMed database between March 29 and April 16, 2022, using the phrases "long-covid," "post-COVID syndrome," "Vitamin D covid," "vitamin C covid," "omega-3 covid," "kynurenine covid," "whole-body hyperthermia," "mushrooms immunity," "n-acetyl cysteine covid," "mushrooms cognition," "sugar consumption inflammation," and "covid microbiome." Articles were screened for their relevance to the discussion of post-COVID syndrome's neurological and psychiatric pathophysiology at the discretion of the principal researcher. There were no limitations regarding publication years, but articles from 2005 to April 2022 were cited. Micro-ischemic disease, neuropathy, autoimmune processes, mast-cell activation, and impaired blood-brain barriers have all been implicated in the pathological processes of this syndrome with varying degrees of supportive evidence. The common denominators, however, are inflammation and oxidative stress. Therefore, a beneficial approach to dealing with the complications of post-COVID syndrome would be to reduce the exacerbations of these common denominators with lifestyle and nutritional changes. Replenishing nutritional deficiencies, supplementing with N-acetylcysteine, decreasing consumption of refined sugars, preventing dysbiosis of the microbiome, performing exercises, increasing dietary intake of mushrooms, utilizing beneficial herbs such as rosemary, and increasing the core body temperature through whole-body hyperthermia seem to show potential for efficacy in this pursuit. Considering the safety and evidence-based connections of the therapies explored for dealing with the post-Covid syndrome, it could be of great benefit and of little harm to our patients to include these considerations in formulating post-Covid treatment plans.}, } @article {pmid38269049, year = {2024}, author = {Yoon, H and Li, Y and Goldfeld, KS and Cobb, GF and Sturm-Reganato, CL and Ostrosky-Zeichner, L and Jayaweera, DT and Philley, JV and Desruisseaux, MS and Keller, MJ and Hochman, JS and Pirofski, LA and Ortigoza, MB and , }, title = {COVID-19 Convalescent Plasma Therapy: Long-term Implications.}, journal = {Open forum infectious diseases}, volume = {11}, number = {1}, pages = {ofad686}, pmid = {38269049}, issn = {2328-8957}, support = {UL1 TR001445/TR/NCATS NIH HHS/United States ; UM1 TR004556/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: The long-term effect of coronavirus disease 2019 (COVID-19) acute treatments on postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is unknown. The CONTAIN-Extend study explores the long-term impact of COVID-19 convalescent plasma (CCP) therapy on postacute sequelae of SARS-CoV-2 infection (PASC) symptoms and general health 18 months following hospitalization.

METHODS: The CONTAIN-Extend study examined 281 participants from the original CONTAIN COVID-19 trial (CONTAIN-RCT, NCT04364737) at 18 months post-hospitalization for acute COVID-19. Symptom surveys, global health assessments, and biospecimen collection were performed from November 2021 to October 2022. Multivariable logistic and linear regression estimated associations between the randomization arms and self-reported symptoms and Patient-Reported Outcomes Measurement Information System (PROMIS) scores and adjusted for covariables, including age, sex, race/ethnicity, disease severity, and CONTAIN enrollment quarter and sites.

RESULTS: There were no differences in symptoms or PROMIS scores between CCP and placebo (adjusted odds ratio [aOR] of general symptoms, 0.95; 95% CI, 0.54-1.67). However, females (aOR, 3.01; 95% CI, 1.73-5.34), those 45-64 years (aOR, 2.55; 95% CI, 1.14-6.23), and April-June 2020 enrollees (aOR, 2.39; 95% CI, 1.10-5.19) were more likely to report general symptoms and have poorer PROMIS physical health scores than their respective reference groups. Hispanic participants (difference, -3.05; 95% CI, -5.82 to -0.27) and Black participants (-4.48; 95% CI, -7.94 to -1.02) had poorer PROMIS physical health than White participants.

CONCLUSIONS: CCP demonstrated no lasting effect on PASC symptoms or overall health in comparison to the placebo. This study underscores the significance of demographic factors, including sex, age, and timing of acute infection, in influencing symptom reporting 18 months after acute hypoxic COVID-19 hospitalization.}, } @article {pmid38268376, year = {2024}, author = {Bopp, K and Meienberg, A}, title = {[Not Available].}, journal = {Revue medicale suisse}, volume = {20}, number = {858}, pages = {178-179}, doi = {10.53738/REVMED.2024.20.858.178}, pmid = {38268376}, issn = {1660-9379}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Drug Treatment ; }, } @article {pmid38267519, year = {2024}, author = {do Amaral, CMSSB and da Luz Goulart, C and da Silva, BM and Valente, J and Rezende, AG and Fernandes, E and Cubas-Vega, N and Borba, MGS and Sampaio, V and Monteiro, W and de Melo, GC and Lacerda, M and Arêas, GPT and Almeida-Val, F}, title = {Low handgrip strength is associated with worse functional outcomes in long COVID.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2049}, pmid = {38267519}, issn = {2045-2322}, support = {002/2008//Fundação de Amparo à Pesquisa do Estado do Amazonas/ ; 007/2018//Fundação de Amparo à Pesquisa do Estado do Amazonas/ ; 005/2019//Fundação de Amparo à Pesquisa do Estado do Amazonas/ ; 005/2022//Fundação de Amparo à Pesquisa do Estado do Amazonas/ ; }, mesh = {Male ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Hand Strength ; Ambulatory Care Facilities ; Body Composition ; }, abstract = {The diagnosis of long COVID is troublesome, even when functional limitations are present. Dynapenia is the loss of muscle strength and power production that is not caused by neurologic or muscular diseases, being mostly associated with changes in neurologic function and/or the intrinsic force-generating properties of skeletal muscle, which altogether, may partially explain the limitations seen in long COVID. This study aimed to identify the distribution and possible associations of dynapenia with functional assessments in patients with long COVID. A total of 113 patients with COVID-19 were evaluated by functional assessment 120 days post-acute severe disease. Body composition, respiratory muscle strength, spirometry, six-minute walk test (6MWT, meters), and hand-grip strength (HGS, Kilogram-force) were assessed. Dynapenia was defined as HGS < 30 Kgf (men), and < 20 Kgf (women). Twenty-five (22%) participants were dynapenic, presenting lower muscle mass (p < 0.001), worse forced expiratory volume in the first second (FEV1) (p = 0.0001), lower forced vital capacity (p < 0.001), and inspiratory (p = 0.007) and expiratory (p = 0.002) peek pressures, as well as worse 6MWT performance (p < 0.001). Dynapenia, independently of age, was associated with worse FEV1, maximal expiratory pressure (MEP), and 6MWT, (p < 0.001) outcomes. Patients with dynapenia had higher intensive care unit (ICU) admission rates (p = 0.01) and need for invasive mechanical ventilation (p = 0.007) during hospitalization. The HGS is a simple, reliable, and low-cost measurement that can be performed in outpatient clinics in low- and middle-income countries. Thus, HGS may be used as a proxy indicator of functional impairment in this population.}, } @article {pmid38266043, year = {2024}, author = {Panagi, L and White, SR and Pinto Pereira, SM and Nugawela, MD and Heyman, I and Sharma, K and Stephenson, T and Chalder, T and Rojas, NK and Dalrymple, E and McOwat, K and Simmons, R and Swann, O and , and Ford, T and Shafran, R}, title = {Mental health in the COVID-19 pandemic: A longitudinal analysis of the CLoCk cohort study.}, journal = {PLoS medicine}, volume = {21}, number = {1}, pages = {e1004315}, pmid = {38266043}, issn = {1549-1676}, support = {MC_UU_00002/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Female ; Humans ; Adolescent ; *COVID-19/epidemiology ; Cohort Studies ; Mental Health ; Longitudinal Studies ; SARS-CoV-2 ; Pandemics ; COVID-19 Testing ; }, abstract = {BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories.

METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p < 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias.

CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.}, } @article {pmid38262969, year = {2024}, author = {Gruber, R and Montilva Ludewig, MV and Weßels, C and Schlang, G and Jedhoff, S and Herbrandt, S and Mattner, F}, title = {Long-term symptoms after SARS-CoV-2 infection in a cohort of hospital employees: duration and predictive factors.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {119}, pmid = {38262969}, issn = {1471-2334}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Personnel, Hospital ; *Ageusia ; Hospitals ; }, abstract = {PURPOSE: To evaluate the frequency, duration and patterns of long-term coronavirus disease 2019 (COVID-19) symptoms and to analyse risk factors for long-lasting COVID-19 sequelae among a cohort of hospital employees (HEs).

METHODS: We conducted a survey regarding persistent COVID-19 related symptoms with all HEs from three medical centres in Cologne, Germany, who were tested SARS-CoV-2 PCR positive from March 2020 until May 2021. Duration of symptoms and possible risk factors for protracted COVID-19 course were analysed.

RESULTS: Of 221 included HEs, a number of 104 HEs (47.1%) reported at least one persisting symptom for more than 90 days after initial SARS-CoV-2 detection. Each one cycle higher initial Ct value significantly increased the chances of overcoming symptoms (odds ratio [OR] 1.05; 95% confidence interval (95%CI) 1.01-1.09; p = 0.019). The occurrence of breathlessness within the first ten days (OR 7.89; 95%CI 1.87-41.43; p = 0.008), an initial Ct value under 30 (OR 3.36; 95%CI 1.22-9.94; p = 0.022) as well as the occurrence of anosmia or ageusia within the first ten days (OR 3.01; 95%CI 1.10-8.84; p = 0.037) showed a statistically significant association with increased odds of illness duration over 90 days.

CONCLUSION: About half of the HEs suffered from long lasting symptoms over 90 days after almost entirely mild acute COVID-19. Predictive factors could possibly be used for early treatment to prevent development of long-term symptoms after COVID-19 in future.}, } @article {pmid38262421, year = {2024}, author = {Grote, H and Hoffmann, A and Kerzel, S and Lukasik, H and Maier, C and Mallon, C and Schlegtendal, A and Schwarzbach, M and van Ackeren, K and Volkenstein, S and Brinkmann, F}, title = {Subjective Smell Disturbances in Children with Sars-Cov-2 or Other Viral Infections do not Correspond with Olfactory Test Results.}, journal = {Klinische Padiatrie}, volume = {236}, number = {2}, pages = {129-138}, doi = {10.1055/a-2208-6245}, pmid = {38262421}, issn = {1439-3824}, mesh = {Child ; Humans ; SARS-CoV-2 ; Smell ; *COVID-19/diagnosis/complications ; Post-Acute COVID-19 Syndrome ; Anosmia/complications ; *Olfaction Disorders/diagnosis/complications ; }, abstract = {BACKGROUND: Olfactory dysfunction associated with SARS-CoV-2 infection in children has not been verified by a validated olfactory test. We aimed to determine whether these complaints are objectifiable (test-based hyposmia), how often they occur during acute SARS-CoV-2 infection compared to other upper respiratory tract infections (URTI), as well as in children recovered from COVID-19 compared to children with long COVID.

METHODS: Olfactory testing (U-sniff test; hyposmia<8 points) and survey-based symptom assessments were performed in 434 children (5-17 years; 04/2021-06/2022). 186 symptom-free children served as controls. Of the children with symptoms of acute respiratory tract infection, SARS-CoV-2 PCR test results were positive in 45 and negative in 107 children (URTI group). Additionally, 96 children were recruited at least 4 weeks (17.6±15.2 weeks) after COVID-19, of whom 66 had recovered and 30 had developed long COVID.

RESULTS: Compared to controls (2.7%), hyposmia frequency was increased in all other groups (11-17%, p<0.05), but no between-group differences were observed. Only 3/41 children with hyposmia reported complaints, whereas 13/16 children with complaints were normosmic, with the largest proportion being in the long-COVID group (23%, p<0.05).

CONCLUSION: Questionnaires are unsuitable for assessing hyposmia frequency in children. Olfactory complaints and hyposmia are not specific for SARS-CoV-2 infection. The number of complaints in the long-COVID group could result from aversive olfactory perception, which is undetectable with the U-sniff test.}, } @article {pmid38260669, year = {2024}, author = {Reagin, KL and Lee, RL and Cocciolone, L and Funk, KE}, title = {Antigen non-specific CD8[+] T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38260669}, issn = {2692-8205}, support = {75N92020D00005/HL/NHLBI NIH HHS/United States ; 75N93022D00005/AI/NIAID NIH HHS/United States ; 75N99020D00005/OF/ORFDO NIH HHS/United States ; 75N95020D00005/DA/NIDA NIH HHS/United States ; R00 AG053412/AG/NIA NIH HHS/United States ; 75N93023D00005/AI/NIAID NIH HHS/United States ; }, abstract = {Primarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed "long COVID". Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8[+] T cells within the brains of aged animals but reduced antigen specificity of those CD8[+] T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8[+] T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8[+] T cell-derived IFN-γ correlated with neuronal death. These results support the evidence that CD8[+] T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals.}, } @article {pmid38260531, year = {2024}, author = {Singh, A and Adam, A and Aditi, and Peng, BH and Yu, X and Zou, J and Kulkarni, VV and Kan, P and Jiang, W and Shi, PY and Samir, P and Cisneros, I and Wang, T}, title = {A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.03.574064}, pmid = {38260531}, issn = {2692-8205}, abstract = {Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.}, } @article {pmid38260484, year = {2024}, author = {Grady, CB and Bhattacharjee, B and Silva, J and Jaycox, J and Lee, LW and Monteiro, VS and Sawano, M and Massey, D and Caraballo, C and Gehlhausen, JR and Tabachnikova, A and Mao, T and Lucas, C and Peña-Hernandez, MA and Xu, L and Tzeng, TJ and Takahashi, T and Herrin, J and Güthe, DB and Akrami, A and Assaf, G and Davis, H and Harris, K and McCorkell, L and Schulz, WL and Grffin, D and Wei, H and Ring, AM and Guan, L and Cruz, CD and Iwasaki, A and Krumholz, HM}, title = {Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38260484}, support = {R01 AI157488/AI/NIAID NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; }, abstract = {BACKGROUND: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology.

METHODS: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination.

RESULTS: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes.

CONCLUSIONS: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.}, } @article {pmid38260287, year = {2024}, author = {Ashok, D and Liu, T and Criscione, J and Prakash, M and Kim, B and Chow, J and Craney, M and Papanicolaou, KN and Sidor, A and Brian Foster, D and Pekosz, A and Villano, J and Kim, DH and O'Rourke, B}, title = {Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.05.574280}, pmid = {38260287}, issn = {2692-8205}, abstract = {BACKGROUND: Cardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19.

METHODS: Radiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection.

RESULTS: COVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca [2+] handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant.

CONCLUSIONS: The findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.}, } @article {pmid38260089, year = {2024}, author = {Ach, T and Ben Haj Slama, N and Gorchane, A and Ben Abdelkrim, A and Garma, M and Ben Lasfar, N and Bellazreg, F and Debbabi, W and Hachfi, W and Chadli Chaieb, M and Zaouali, M and Letaief, A and Ach, K}, title = {Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis.}, journal = {Journal of the Endocrine Society}, volume = {8}, number = {3}, pages = {bvae003}, pmid = {38260089}, issn = {2472-1972}, abstract = {CONTEXT: In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised.

OBJECTIVE: Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing post-COVID-19 syndrome to detect any deficiencies that may explain long COVID.

METHODS: A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised fully recovered patients, while the second group (G2) included patients experiencing long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions.

RESULTS: A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P = .045): for the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (P = .045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P = .01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P = .369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P = .041).

CONCLUSION: The results showed that long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain long COVID.}, } @article {pmid38260018, year = {2023}, author = {Yasir, S and Jin, Y and Razzaq, FA and Caballero-Moreno, A and Galán-García, L and Ren, P and Valdes-Sosa, M and Rodriguez-Labrada, R and Bringas-Vega, ML and Valdes-Sosa, PA}, title = {The determinants of COVID-induced brain dysfunctions after SARS-CoV-2 infection in hospitalized patients.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1249282}, pmid = {38260018}, issn = {1662-4548}, abstract = {The severity of the pandemic and its consequences on health and social care systems were quite diverse and devastating. COVID-19 was associated with an increased risk of neurological and neuropsychiatric disorders after SARS-CoV-2 infection. We did a cross-sectional study of 3 months post-COVID consequences of 178 Cuban subjects. Our study has a unique CUBAN COVID-19 cohort of hospitalized COVID-19 patients and healthy subjects. We constructed a latent variable for pre-health conditions (PHC) through Item Response Theory (IRT) and for post-COVID neuropsychiatric symptoms (Post-COVID-NPS) through Factor Analysis (FA). There seems to be a potential causal relationship between determinants of CIBD and post-COVID-NPS in hospitalized COVID-19 patients. The causal relationships accessed by Structural Equation Modeling (SEM) revealed that PHC (p < 0.001) and pre-COVID cognitive impairments (p < 0.001) affect the severity of COVID-19 patients. The severity of COVID-19 eventually results in enhanced post-COVID-NPS (p < 0.001), even after adjusting for confounders (age, sex, and pre-COVID-NPS). The highest loadings in PHC were for cardiovascular diseases, immunological disorders, high blood pressure, and diabetes. On the other hand, sex (p < 0.001) and pre-COVID-NPS including neuroticism (p < 0.001), psychosis (p = 0.005), cognition (p = 0.036), and addiction (p < 0.001) were significantly associated with post-COVID-NPS. The most common neuropsychiatric symptom with the highest loadings includes pain, fatigue syndrome, autonomic dysfunctionalities, cardiovascular disorders, and neurological symptoms. Compared to healthy people, COVID-19 patients with pre-health comorbidities or pre-neuropsychiatric conditions will have a high risk of getting severe COVID-19 and long-term post-COVID neuropsychiatric consequences. Our study provides substantial evidence to highlight the need for a complete neuropsychiatric follow-up on COVID-19 patients (with severe illness) and survivors (asymptomatic patients who recovered).}, } @article {pmid38259488, year = {2023}, author = {Yoon, H and Dean, LS and Jiyarom, B and Khadka, VS and Deng, Y and Nerurkar, VR and Chow, DC and Shikuma, CM and Devendra, G and Koh, Y and Park, J}, title = {Single-cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1268510}, pmid = {38259488}, issn = {1664-3224}, support = {U54 MD007601/MD/NIMHD NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 GM138062/GM/NIGMS NIH HHS/United States ; T37 MD008636/MD/NIMHD NIH HHS/United States ; P20 GM103466/GM/NIGMS NIH HHS/United States ; P20 GM139753/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/genetics ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; Vascular Endothelial Growth Factor A ; Myeloid Cells ; *Pulmonary Fibrosis/genetics ; Disease Progression ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Although our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complications in COVID-19 infection remains unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequelae of SARS-CoV-2 infection (PASC) with persistent pulmonary symptoms. The dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown.

RESULTS: To characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing (scRNA-seq) to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from a participant naïve to SARS-CoV-2 (Control) (n=1) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC) (n=2). After integrating scRNA-seq data with a naïve participant from a published dataset, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14[+]/CD16[+]monocytes, and dendritic cells) was increased in PPASC (n=2) compared to controls (n=2). MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis-related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. Further comparison of PPASC with scRNA-seq data with Severe COVID-19 (n=4) data demonstrated enrichment of fibrotic transcriptional signatures. In PPASC, we observed interactive VEGF ligand-receptor pairs among MLCs, and network modules in CD14[+] (cluster 4) and CD16[+] (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID-19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS-CoV-2 naïve samples.

CONCLUSION: Analysis of a small scRNA-seq dataset demonstrated alterations in the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests a potential role in PPASC development.}, } @article {pmid38258769, year = {2024}, author = {Hodel, K and Fonseca, A and Barbosa, I and Medina, C and Alves, B and Maciel, C and Nascimento, D and Oliveira-Junior, G and Pedreira, L and de Souza, M and Godoy, AL}, title = {Obesity and its Relationship with Covid-19: A Review of the Main Pharmaceutical Aspects.}, journal = {Current pharmaceutical biotechnology}, volume = {25}, number = {13}, pages = {1651-1663}, pmid = {38258769}, issn = {1873-4316}, mesh = {Humans ; *Obesity/metabolism ; *COVID-19/complications ; *COVID-19 Drug Treatment ; *SARS-CoV-2 ; Antiviral Agents/therapeutic use/pharmacokinetics ; COVID-19 Vaccines ; }, abstract = {Important physiological changes are observed in patients with obesity, such as intestinal permeability, gastric emptying, cardiac output, and hepatic and renal function. These differences can determine variations in the pharmacokinetics of different drugs and can generate different concentrations at the site of action, which can lead to sub therapeutic or toxic concentrations. Understanding the physiological and immunological processes that lead to the clinical manifestations of COVID-19 is essential to correlate obesity as a risk factor for increasing the prevalence, severity, and lethality of the disease. Several drugs have been suggested to control COVID- 19 like Lopinavir, Ritonavir, Ribavirin, Sofosbuvir, Remdesivir, Oseltamivir, Oseltamivir phosphate, Oseltamivir carboxylate, Hydroxychloroquine, Chloroquine, Azithromycin, Teicoplanin, Tocilizumab, Anakinra, Methylprednisolone, Prednisolone, Ciclesonide and Ivermectin. Similarly, these differences between healthy people and obese people can be correlated to mechanical factors, such as insufficient doses of the vaccine for high body mass, impairing the absorption and distribution of the vaccine that will be lower than desired or can be linked to the inflammatory state in obese patients, which can influence the humoral immune response. Additionally, different aspects make the obese population more prone to persistent symptoms of the disease (long COVID), which makes understanding these mechanisms fundamental to addressing the implications of the disease. Thus, this review provides an overview of the relationship between COVID-19 and obesity, considering aspects related to pharmacokinetics, immunosuppression, immunization, and possible implications of long COVID in these individuals.}, } @article {pmid38257821, year = {2024}, author = {Panagiotides, NG and Poledniczek, M and Andreas, M and Hülsmann, M and Kocher, AA and Kopp, CW and Piechota-Polanczyk, A and Weidenhammer, A and Pavo, N and Wadowski, PP}, title = {Myocardial Oedema as a Consequence of Viral Infection and Persistence-A Narrative Review with Focus on COVID-19 and Post COVID Sequelae.}, journal = {Viruses}, volume = {16}, number = {1}, pages = {}, pmid = {38257821}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Virus Diseases ; Disease Progression ; Edema ; }, abstract = {Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.}, } @article {pmid38257782, year = {2024}, author = {Spinello, I and Saulle, E and Quaranta, MT and Pelosi, E and Castelli, G and Cerio, A and Pasquini, L and Morsilli, O and Dupuis, ML and Labbaye, C}, title = {AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4.}, journal = {Viruses}, volume = {16}, number = {1}, pages = {}, pmid = {38257782}, issn = {1999-4915}, support = {NA//Istituto Superiore di Sanità/ ; }, mesh = {Humans ; COVID-19 ; *Megakaryocytes/virology ; *Phenols/pharmacology ; Post-Acute COVID-19 Syndrome ; *Reserpine/analogs & derivatives/pharmacology ; *SARS-CoV-2/drug effects ; Virus Internalization/drug effects ; }, abstract = {Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection in megakaryocytes, which are precursors of platelets involved in thrombotic events in COVID-19, long COVID and, in rare cases, in vaccinated individuals, requires further investigation, particularly with the emergence of new SARS-CoV-2 variants. CD147, involved in the regulation of inflammation and required to fight virus infection, can facilitate SARS-CoV-2 entry into megakaryocytes. MCT4, a co-binding protein of CD147 and a key player in the glycolytic metabolism, could also play a role in SARS-CoV-2 infection. Here, we investigated the susceptibility of megakaryocytes to SARS-CoV-2 infection via CD147 and MCT4. We performed infection of Dami cells and human CD34[+] hematopoietic progenitor cells induced to megakaryocytic differentiation with SARS-CoV-2 pseudovirus in the presence of AC-73 and syrosingopine, respective inhibitors of CD147 and MCT4 and inducers of autophagy, a process essential in megakaryocyte differentiation. Both AC-73 and syrosingopine enhance autophagy during differentiation but only AC-73 enhances megakaryocytic maturation. Importantly, we found that AC-73 or syrosingopine significantly inhibits SARS-CoV-2 infection of megakaryocytes. Altogether, our data indicate AC-73 and syrosingopine as inhibitors of SARS-CoV-2 infection via CD147 and MCT4 that can be used to prevent SARS-CoV-2 binding and entry into megakaryocytes, which are precursors of platelets involved in COVID-19-associated coagulopathy.}, } @article {pmid38257728, year = {2023}, author = {Len, JS and Koh, CWT and Chan, KR}, title = {The Functional Roles of MDSCs in Severe COVID-19 Pathogenesis.}, journal = {Viruses}, volume = {16}, number = {1}, pages = {}, pmid = {38257728}, issn = {1999-4915}, support = {MOH-000610-00//National Medical Research Council/ ; }, mesh = {Aged ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Myeloid-Derived Suppressor Cells ; Gene Expression Profiling ; Immunocompromised Host ; }, abstract = {Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially among those with co-morbidities, the elderly, and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analyses of transcriptomic RNAseq and single-cell sequencing datasets comparing severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could be a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examine the existing literature summarizing the characteristics of MDSCs, provide evidence of MDSCs in facilitating severe COVID-19 pathogenesis, and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualize the temporal changes in specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution, based on our previous study.}, } @article {pmid38256566, year = {2024}, author = {Lim, KR and Chun, KJ and Kim, BS and Lee, S}, title = {The Effect of Sodium-Glucose Cotransporter-2 Inhibitors on COVID-19 Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using the Common Data Model.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256566}, issn = {2077-0383}, support = {//2023 Kangwon National University Hospital Grant/ ; }, abstract = {BACKGROUND: There is no clinical evidence about the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diabetic patients who have been diagnosed with coronavirus disease 19 (COVID-19).

METHODS: The dataset is based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea from January, 2018 to April, 2022. Among 9,822,577 patients who were involved in the claims, diabetic patients were divided into two groups based on whether they had a prescription for an SGLT2 inhibitor. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs), which were a composite of all-cause mortality, myocardial infarction, stroke, and revascularization over 90 days.

RESULTS: A total of 172,682 patients was analyzed. In the propensity score-matched analysis, the rate of MACCE was lower in the SGLT2 inhibitor group compared to the non-SGLT2 inhibitor group (0.89% vs. 1.31%; hazard ratio, 0.71; 95% confidence interval, 0.53-0.94; p =0.020). Each of the MACCEs showed no differences between the two groups. The rate of pneumonia was similar between the two groups (4.45% vs. 4.39%; hazard ratio, 1.06; 95% confidence interval, 0.91-1.16; p = 0.620).

CONCLUSIONS: In the diabetic patients who were diagnosed with COVID-19, SGLT2 inhibitors were associated with improved clinical outcomes in terms of MACCEs. SGLT2 inhibitors might be considered for prescription to diabetic patients in the current context of long COVID-19.}, } @article {pmid38256559, year = {2024}, author = {Pietranis, KA and Izdebska, WM and Kuryliszyn-Moskal, A and Dakowicz, A and Ciołkiewicz, M and Kaniewska, K and Dzięcioł-Anikiej, Z and Wojciuk, M}, title = {Effects of Pulmonary Rehabilitation on Respiratory Function and Thickness of the Diaphragm in Patients with Post-COVID-19 Syndrome: A Randomized Clinical Trial.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256559}, issn = {2077-0383}, abstract = {BACKGROUND: Rehabilitation is an effective method for improving the overall health of patients who have experienced the long-term effects of COVID-19.

METHODS: The double-blind, randomized prospective study assessed the effectiveness of a 6-week rehabilitation program among post-COVID-19 patients. A total of 59 patients under treatment following COVID-19 were randomly divided into two groups. Both groups completed the same six-week comprehensive exercise training program supported by a respiratory muscle trainer (Threshold IMT) during out-patient sessions. The control group performed placebo IMT. Respiratory muscle strength, chest wall expansion, spirometry, and diaphragm ultrasonography measurements were taken before and after the six weeks.

RESULTS: The applied rehabilitation program improved respiratory muscle strength in both the study and control groups (p < 0.001). There was a significant chest circumference increase in the study group (p < 0.001). Spirometric parameters improved in both groups, with the study group showing a greater improvement: 8.02% in FEV1 (p < 0.001), 13.24% in FVC EX (p < 0.001) and 9.67% in PEF (p < 0.001). Rehabilitation also increased diaphragm thickness during maximum inhalation in both groups.

CONCLUSIONS: Based on the study findings, the specialized outpatient rehabilitation program developed for post-COVID-19 patients has proven to be effective and safe.}, } @article {pmid38256558, year = {2024}, author = {Kao, CM}, title = {Overview of COVID-19 Infection, Treatment, and Prevention in Children.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256558}, issn = {2077-0383}, abstract = {Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.}, } @article {pmid38256526, year = {2024}, author = {Pappas, AG and Eleftheriou, K and Vlahakos, V and Magkouta, SF and Riba, T and Dede, K and Siampani, R and Kompogiorgas, S and Polydora, E and Papalampidou, A and Loutsidi, NE and Mantas, N and Tavernaraki, E and Exarchos, D and Kalomenidis, I}, title = {High Plasma Osteopontin Levels Are Associated with Serious Post-Acute-COVID-19-Related Dyspnea.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38256526}, issn = {2077-0383}, abstract = {COVID-19 survivors commonly report persistent symptoms. In this observational study, we investigated the link between osteopontin (OPN) and post-acute COVID-19 symptoms and lung functional/imaging abnormalities. We recorded symptoms and lung imaging/functional data from previously hospitalized COVID-19 patients, who were followed for 4-84 weeks (122 patients/181 visits) post-symptom onset at our outpatient clinic. Circulating OPN was determined using ELISA. Plasma OPN levels were higher in symptomatic patients (compared with the asymptomatic ones); those with dyspnea (compared with those without dyspnea);those with a combination of serious symptoms, i.e., the presence of at least one of the following: dyspnea, fatigue and muscular weakness (compared with those with none of these symptoms); and those with dyspnea and m-MRC > 1 (compared with those with m-MRC = 0-1). Plasma OPN levels were inversely correlated with EQ-VAS (visual analog scale of the EQ-5D-5L health-related quality-of-life questionnaire) values. High-resolution CT or diffusion lung capacity (DLCO) findings were not related to circulating OPN. In the multiple logistic regression, the presence of symptoms, dyspnea, or the combination of serious symptoms were linked to female gender, increased BMI and pre-existing dyspnea (before the acute disease), while increased plasma OPN levels, female gender and pre-existing dyspnea with m-MRC > 1 were independently associated with severe post-COVID-19 dyspnea (m-MRC > 1). Using a correlation matrix to investigate multiple correlations between EQ-VAS, OPN and epidemiological data, we observed an inverse correlation between the OPN and EQ-VAS values. Increased circulating OPN was linked to the persistence of severe exertional dyspnea and impaired quality of life in previously hospitalized COVID-19 patients.}, } @article {pmid38256314, year = {2023}, author = {Cojocaru, DC and Mitu, F and Leon, MM and Dima-Cozma, LC and Adam, CA and Cumpăt, CM and Negru, RD and Maștaleru, A and Onofrei, V}, title = {Beyond the Acute Phase: Long-Term Impact of COVID-19 on Functional Capacity and Prothrombotic Risk-A Pilot Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {1}, pages = {}, pmid = {38256314}, issn = {1648-9144}, mesh = {Female ; Humans ; Middle Aged ; Aged ; Male ; *COVID-19/complications ; Pilot Projects ; *Pulmonary Fibrosis ; Retrospective Studies ; Ambulatory Care Facilities ; }, abstract = {Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m[2]). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm[3] vs. 9.18 ± 17.24/mm[3], p = 0.053), neutrophils (4.68 ± 7.88/mm[3] vs. 9.07 ± 17.44/mm[3], p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.}, } @article {pmid38255826, year = {2024}, author = {Müller, L and Di Benedetto, S}, title = {Immunosenescence and Cytomegalovirus: Exploring Their Connection in the Context of Aging, Health, and Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38255826}, issn = {1422-0067}, mesh = {Aged ; Humans ; Cytomegalovirus ; Post-Acute COVID-19 Syndrome ; Aging ; *Immunosenescence ; *Cytomegalovirus Infections ; *COVID-19 ; *Latent Infection ; }, abstract = {Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting profound questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases. This review delves into the intricate relationship between immunosenescence and CMV, revealing how chronic viral infection impacts the aging immune landscape. We explore the mechanisms through which CMV can impact both the composition and functionality of immune cell populations and induce shifts in inflammatory profiles with aging. Moreover, we examine the potential role of CMV in pathologies such as cardiovascular diseases, cancer, neurodegenerative disorders, COVID-19, and Long COVID. This review underlines the importance of understanding the complex interplay between immunosenescence and CMV. It offers insights into the pathophysiology of aging and age-associated diseases, as well as COVID-19 outcomes among the elderly. By unraveling the connections between immunosenescence and CMV, we gain a deeper understanding of aging's remarkable journey and the profound role that viral infections play in transforming the human immune system.}, } @article {pmid38255418, year = {2024}, author = {Mariani, F and Rainaldi, S and Dall'Ara, G and De Rose, C and Morello, R and Buonsenso, D}, title = {Persisting Gastrointestinal Symptoms in Children with SARS-CoV-2: Temporal Evolution over 18 Months and Possible Role of Lactoferrin.}, journal = {Children (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {38255418}, issn = {2227-9067}, abstract = {BACKGROUND AND AIM: Persisting gastrointestinal symptoms are reported to be relatively common in children with long COVID; however, their detailed characterization and long-term outcomes have not yet been described.

METHODS: We performed a retrospective study aiming to investigate the temporal evolution of gastrointestinal symptoms in children with SARS-CoV-2, from acute infection to 18-months follow-up. To further investigate possible therapeutic strategies, we evaluated the role of lactoferrin in improving gastrointestinal symptoms in these children, compared with those not treated.

RESULTS: A total of 1224 patients (47.7% females) were included. Of these participants, 246 (19.8%) were vaccinated and 143 (11.5%) presented with comorbidities. A total of 175 patients (14.1%) presented gastrointestinal symptoms during acute infection, 54 (4.4%) at three months, 23 (1.9%) at six months, 6 (3.3%) at twelve months, and 2 (2.3%) at eighteen months follow-up. At six months follow-up, children who were treated with 3 months oral lactoferrin had less persisting symptoms compared to those who did not receive lactoferrin, although this difference was not statistically significant (three patients (25%) in the lactoferrin group vs. fourteen patients (33.3%) not treated, p = 0.73), probably due to the low number of patients with persisting GI symptoms.

CONCLUSIONS: GI symptoms are relatively common during acute SARS-CoV-2 infection in children, and a non-negligible proportion of these children reported persisting symptoms for up to 12-18 months after the acute infection. In addition, we found a trend even if statistically nonsignificant toward faster improvement of persisting gastrointestinal symptoms in children with long COVID treated with lactoferrin. Despite the limitations relating to the present study's design, given the significant burden of gastrointestinal symptoms in children with long COVID, our findings provide the basis to perform a prospective, placebo-controlled study.}, } @article {pmid38255039, year = {2024}, author = {Weise, A and Ott, E and Hersche, R}, title = {Energy Management Education in Persons with Long COVID-Related Fatigue: Insights from Focus Group Results on Occupational Therapy Approach.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {38255039}, issn = {2227-9032}, support = {no//Swiss Occupational Therapy Association/ ; no//Swiss OT Trust/ ; }, abstract = {BACKGROUND: Long COVID is a growing condition among individuals, with fatigue being one of the main symptoms experienced. Energy Management Education (EME) is a structured occupational therapy group intervention that aims to reduce the impact of fatigue in daily life.

METHODS: This study utilized focus groups to explore the experiences of individuals with post-COVID-related fatigue who participated in the EME program. Six participants engaged in discussions about the program immediately after its completion and again two months later. Additionally, five occupational therapists shared their experiences.

RESULTS: Former participants reported implementing strategies learned in the program to manage their condition effectively. They emphasized the importance of understanding fatigue and found the support provided by the peer group valuable. Occupational therapists highlighted the unique challenges faced by individuals with post-COVID-related fatigue compared to other populations with similar fatigue symptoms. Furthermore, insights were obtained regarding the ways individuals live and cope with post-COVID-related fatigue.

CONCLUSION: EME participants were involved in a dynamic and complex occupational therapy process and were experiencing a slow change towards having more control over their daily routines. The study gathered valuable feedback and suggestions from participants and occupational therapists which can be used to optimize the EME program.}, } @article {pmid38253027, year = {2024}, author = {Untersmayr, E and Venter, C and Smith, P and Rohrhofer, J and Ndwandwe, C and Schwarze, J and Shannon, E and Sokolowska, M and Sadlier, C and O'Mahony, L}, title = {Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.}, journal = {International archives of allergy and immunology}, volume = {185}, number = {5}, pages = {489-502}, doi = {10.1159/000535736}, pmid = {38253027}, issn = {1423-0097}, mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *Post-Acute COVID-19 Syndrome ; Dysbiosis/immunology ; Autoimmunity ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection.

SUMMARY: In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors.

KEY MESSAGES: Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.}, } @article {pmid38252638, year = {2024}, author = {Leitner, M and Pötz, G and Berger, M and Fellner, M and Spat, S and Koini, M}, title = {Characteristics and burden of acute COVID-19 and long-COVID: Demographic, physical, mental health, and economic perspectives.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0297207}, pmid = {38252638}, issn = {1932-6203}, mesh = {Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Mental Health ; Acute Disease ; Dyspnea ; Fatigue ; Memory Disorders ; Mental Fatigue ; Demography ; }, abstract = {BACKGROUND: COVID-19 infection and its associated consequence, known as long-COVID, lead to a significant burden on the global healthcare system and limitations in people's personal and work lives. This study aims to provide further insight into the impact of acute and ongoing COVID-19 symptoms and investigates the role of patients' gender and vaccination status.

METHODS: 416 individuals (73.9% female) between the ages of 16 and 80 years (M = 44.18, SD = 12.90) with self-reported symptoms of long-COVID participated in an online survey conducted between March and May 2022.

RESULTS: 6.0%, 74.3%, and 19.7% of all respondents reported having had an asymptomatic, mild, or severe acute illness, respectively. Out of all participants, 7.8% required hospitalization. The most prevalent symptoms during the acute infection (Mdn = 23.50 symptoms, IQR = 13-39) included fatigue, exhaustion, cough, brain fog, and memory problems. The median long-COVID disease duration was 12.10 months (IQR = 2.8-17.4). Among 64 inquired long-COVID symptoms (Mdn = 17.00 symptoms, IQR = 9-27), participants reported fatigue, exhaustion, memory problems, brain fog, and dyspnea as the most common ongoing symptoms, which were generally experienced as fluctuating and deteriorating after physical or cognitive activity. Common consequences of long-COVID included financial losses (40.5%), changes in the participants' profession (41.0%), stress resistance (87.5%), sexual life (38.1%), and mood (72.1%), as well as breathing difficulties (41.3%), or an increased drug intake (e.g., medicine, alcohol; 44.6%). In addition, vaccinated individuals exhibited a shorter acute illness duration and an earlier onset of long-COVID symptoms. In general, women reported more long-COVID symptoms than men.

CONCLUSION: Long-COVID represents a heterogeneous disease and impacts multiple life aspects of those affected. Tailored rehabilitation programs targeting the plurality of physical and mental symptoms are needed.}, } @article {pmid38250912, year = {2024}, author = {Nguyen, KH and Bao, Y and Mortazavi, J and Allen, JD and Chocano-Bedoya, PO and Corlin, L}, title = {Prevalence and Factors Associated with Long COVID Symptoms among U.S. Adults, 2022.}, journal = {Vaccines}, volume = {12}, number = {1}, pages = {}, pmid = {38250912}, issn = {2076-393X}, abstract = {Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors associated with long COVID and the individual symptoms. Prevalence differences were conducted to examine differences in long COVID by vaccination status. Overall, more than one in five adults who ever had COVID-19 reported symptoms consistent with long COVID (21.8%). The most common symptom was tiredness or fatigue (26.2%), followed by difficulty breathing or shortness of breath (18.9%), and loss of taste or smell (17.0%). Long COVID was more common among adults under 65 years, women, American Indian or Alaska Native or other/multi race group, smokers, and people with a disability, depression, overweight or obesity compared to their respective counterparts. The prevalence of long COVID was higher among unvaccinated adults (25.6%) than vaccinated adults (21.6%) overall, and for 20 of 32 subgroups assessed. These findings underscore the benefits of vaccination, the importance of early treatment, and the need to better inform health care resource allocation and support services for those experiencing long COVID.}, } @article {pmid38250080, year = {2023}, author = {Ravkov, EV and Williams, ESCP and Elgort, M and Barker, AP and Planelles, V and Spivak, AM and Delgado, JC and Lin, L and Hanley, TM}, title = {Reduced monocyte proportions and responsiveness in convalescent COVID-19 patients.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1329026}, pmid = {38250080}, issn = {1664-3224}, support = {R01 AI143567/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Monocytes ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Lipopolysaccharides ; }, abstract = {INTRODUCTION: The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We sought to examine the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and nonclassical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients.

METHODS: Peripheral blood mononuclear cells (PBMCs) from convalescent COVID-19 patients and uninfected controls were analyzed by multiparameter flow cytometry to determine relative percentages of total monocytes and monocyte subsets. The expression of activation markers and proinflammatory cytokines in response to LPS treatment were measured by flow cytometry and ELISA, respectively.

RESULTS: We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF-α and IL-6 in response to LPS stimulation, than those from uninfected controls.

CONCLUSION: SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.}, } @article {pmid38249977, year = {2023}, author = {Tana, C}, title = {Editorial: Frailty in older patients during the COVID-19 era.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1348468}, pmid = {38249977}, issn = {2296-858X}, } @article {pmid38249761, year = {2023}, author = {Torres, G and Rains, N and Gradidge, PJ and Constantinou, D}, title = {Exercise intervention for post-acute COVID-19 syndrome - do FITT-VP principles apply? A case study.}, journal = {South African journal of sports medicine}, volume = {35}, number = {1}, pages = {v35i1a15284}, pmid = {38249761}, issn = {2078-516X}, abstract = {The lack of standardisation of reporting exercise interventions hampers the development of best practice guidelines for long COVID patients. This case study on the effect of an exercise intervention in a long COVID patient applied the Consensus on Exercise Reporting Template (CERT) for reporting interventions. FITT-VP exercise prescription principles for long COVID rehabilitation are also suggested. A 58-year-old male, previously hospitalised for 14 days in the ward for the intensive care for the management of severe COVID-19 infection, joined an exercise rehabilitation programme. A medical history, anthropometric, biochemical, lung function, blood pressure, cardiorespiratory fitness and strength measures were all assessed before and after the eight week exercise intervention programme. Positive changes were found in all lung function test measures. Cardiorespiratory fitness, endurance capacity and muscle strength improved. However, the greatest improvements occurred in functional status, fatigue, dyspnoea and the state of depression levels. This case study suggested that in the absence of other instruments, the FITT-VP principles may be used for long COVID patients, and CERT for reporting interventions, but these should be further researched.}, } @article {pmid38249698, year = {2023}, author = {Sathish, T}, title = {New-Onset Diabetes in Long COVID: An Emerging Challenge for the Health System in Low- and Middle-Income Countries.}, journal = {Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine}, volume = {48}, number = {6}, pages = {939-940}, pmid = {38249698}, issn = {0970-0218}, } @article {pmid38249633, year = {2024}, author = {Toru, M and Atnaf, A and Mengist, HM and Reta, A}, title = {The COVID-19 Severity and Its Association with Intestinal Parasite Coinfection and Urine Biochemical Parameters among COVID-19-Confirmed Patients Admitted to Debre Markos University COVID-19 Center, Northwest Ethiopia.}, journal = {BioMed research international}, volume = {2024}, number = {}, pages = {3064374}, pmid = {38249633}, issn = {2314-6141}, mesh = {Humans ; Male ; Female ; Animals ; Middle Aged ; *Parasites ; *Coinfection/epidemiology ; Ethiopia/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Universities ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Intestinal Diseases, Parasitic ; }, abstract = {BACKGROUND: Though most people with COVID-19 disease show asymptomatic to mild illness, a substantial number of patients are at high risk of developing severe disease and adverse outcomes with long COVID-19 and death. Even though some studies showed that previously existing infections with parasites amend the host's body defenses to increase resistance to infection with SARS-CoV-2, there is limited data in Ethiopia.

OBJECTIVES: This study is aimed at determining the COVID-19 disease severity and its association with intestinal parasite coinfection and urine biochemical parameters among COVID-19-confirmed patients admitted at Debre Markos University COVID-19 Center, 2021.

METHODS: A prospective cohort study was conducted on 136 RT-qPCR-confirmed COVID-19 patients admitted at Debre Markos University COVID-19 Center from January 1 to March 30, 2021. Sociodemographic and clinical data were collected by using standardized data collection forms. A urine biochemical test was performed using a dry urine dipstick kit and stool examination using direct wet mount microscopic examination and formalin-ether concentration method. The chi-square test, Fisher exact test, and ordinal logistic regression analysis were computed to assess association with outcome variables using Statistical Package for Social Science software (version 24).

RESULT: A total of 136 COVID-19-confirmed patients participated in this study. The median age of the participants was 48 years. The majority (86 (62.5%)) of them were male in sex. Of the 136 cases, 39 (28.7%) had died. Among the 136 patients, 22 (16.2%) were coinfected with intestinal parasites. COVID-19 patients who have intestinal parasite coinfection had lower odds of developing clinically severe COVID-19 compared to noninfected (AOR = 0.37; 95% CI = 0.147-0.944; P = 0.037). The majority (104 (76.5%)) of them have abnormal urine biochemical results. From the abnormal urine biochemical tests observed, the urine blood, glucose, and ketone tests were positive for 54 (39.7%), 36 (26.5%), and 30 (21.1%) patients, respectively. Among the 31 critical COVID-19 patients, 25 (80.6%) showed abnormal urine biochemical parameters. Age and comorbidity were significantly associated with COVID-19 severity (P < 0.05).

CONCLUSION: Patients with old age and comorbidity had an increased risk of developing severe COVID-19 disease. Patients having SARS-CoV-2 and intestinal parasitic coinfections demonstrated mild COVID-19 disease severity. Abnormal urine biochemical results were common among critical COVID-19 patients. Thus, advanced study on the effect of the interaction among intestinal parasites on COVID-19 clinical severity and its mechanisms is essential.}, } @article {pmid38248798, year = {2024}, author = {Trofor, AC and Robu Popa, D and Melinte, OE and Trofor, L and Vicol, C and Grosu-Creangă, IA and Crișan Dabija, RA and Cernomaz, AT}, title = {Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.}, journal = {Journal of personalized medicine}, volume = {14}, number = {1}, pages = {}, pmid = {38248798}, issn = {2075-4426}, abstract = {Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.}, } @article {pmid38248722, year = {2023}, author = {Melinte, OE and Robu Popa, D and Dobrin, ME and Cernomaz, AT and Grigorescu, C and Nemes, AF and Gradinaru, AC and Vicol, C and Todea, DA and Vulturar, DM and Cioroiu, IB and Trofor, AC}, title = {Assessment of Some Risk Factors and Biological Predictors in the Post COVID-19 Syndrome in Asthmatic Patients.}, journal = {Journal of personalized medicine}, volume = {14}, number = {1}, pages = {}, pmid = {38248722}, issn = {2075-4426}, abstract = {Long COVID-19 or post-COVID infection (PCI) refers to the prolongation of symptoms in people who have been infected with the SARS-CoV-2 virus. Some meta-analysis studies have shown that patients with comorbidities, such as diabetes, obesity or hypertension, have severe complications after infection with the SARS-CoV-2 virus. The presence of chronic respiratory diseases such as bronchial asthma, COPD, pulmonary hypertension or cystic fibrosis increases the risk of developing severe forms of the COVID-19 disease. The risk of developing the severe form of COVID-19 was observed in patients with bronchial asthma being treated with corticosteroids, but also in those hospitalized with severe asthma. The biological variables determined in patients with PCI infection showed changes, especially in the hematological parameters, but also in some inflammatory markers. The aim of this study was to investigate some biological predictors in post-COVID-19 infection in patients with asthma and various comorbidities. In the case of patients diagnosed with moderate and severe forms of COVID-19, the variation in biological tests has shown high concentrations for serum glucose, lactate dehydrogenase and C-reactive protein. Additionally, the calculation of the relative risk (RR) based on the associated comorbidities in patients with PCI points to higher values for patients with asthma, hypertension, diabetes and obesity (RR moderate/severe form = 0.98/1.52), compared to patients with PCI and asthma (RR moderate/severe form = 0.36/0.63). Based on the statistical results, it can be concluded that the alanine aminotransferase (ALT) activity (p = 0.006) and the age of patients (p = 0.001) are the variables that contribute the most to the separation of the four classes of comorbidities considered.}, } @article {pmid38248535, year = {2024}, author = {Misra, R and Kirk, B and Shawley-Brzoska, S and Totzkay, D and Morton, C and Kuhn, S and Harris, M and McMillion, M and Darling, E}, title = {Educational Intervention to Increase COVID-19 Vaccine Uptake in Rural Patients with Chronic Diseases: Lessons Learned from An Innovative Academic-Community Partnership.}, journal = {International journal of environmental research and public health}, volume = {21}, number = {1}, pages = {}, pmid = {38248535}, issn = {1660-4601}, support = {G220984//West Virginia Department of Health and Human Resources/ ; }, mesh = {Adult ; Animals ; Humans ; Female ; Young Adult ; Middle Aged ; Male ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Rural Population ; *COVID-19/prevention & control ; Chronic Disease ; *Coleoptera ; }, abstract = {BACKGROUND: The pandemic has disproportionately impacted rural communities with a higher burden of chronic disease and COVID-19 infection. West Virginia is a rural state with a high rate of diabetes, hypertension, and COPD, which are known risk factors for severe COVID-19 and long COVID. Yet, there is a significant hesitancy regarding COVID-19 vaccination uptake in the state. The purpose of this study was to use an educational intervention to increase vaccine knowledge and vaccine acceptance in rural patients with chronic disease(s) in West Virginia. This project used an academic-community partnership comprised of researchers, practitioners, community organizations, community-engaged partners, and patient stakeholders to increase COVID-19 health literacy and increase vaccine acceptance among rural West Virginians with chronic conditions.

MATERIALS AND METHODS: A quasi-experimental study design was used to deliver an educational intervention by trained Health Navigators using short videos to increase COVID-19 health literacy and address participants' vaccine concerns. Eligibility included adults (18 years and older) who have at least one chronic condition. A statewide community advisory board (CAB) guided the development of the educational training curriculum and implementation strategies. An adapted version of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework guided the development of the intervention. Health Navigators (n = 45) delivered the educational intervention in their local communities between November 2022 and October 2023 (project implementation is still ongoing). Intervention fidelity checks, an adaptable script, and a flow chart allowed tailoring of brief videos to address participants' specific COVID-19 questions and vaccine concerns. A validated online survey, monitored by an online Research Electronic Data Capture (REDCap) database, assessed participants' knowledge, perceived susceptibility, and vaccine intention.

RESULTS: Health Navigators delivered the intervention to 1368 West Virginians in 52 counties (59.2% women; 61.8% without a college degree). Participants reported living with an average of 2.1 ± 1.4 chronic conditions. The mean age was 43.5 ± 18.8 years. The majority of participants (81.2%) had received the primary vaccination series, and 63.1% had at least one booster. However, 18% were unvaccinated or did not complete the primary COVID-19 vaccine series. Discussions to improve vaccine literacy focused on how the vaccine was so quickly developed and protects against variants, addressing concerns related to the safety, short- and long-term side effects, and importance of vaccine uptake for immunocompromised individuals. Participants with higher concerns were more likely to be unvaccinated and to have not completed their primary series or boosters (p < 0.001). However, the educational intervention improved the willingness of individuals who were either unvaccinated or did not complete their primary vaccine series to get vaccinated (11.4%).

DISCUSSION: Our findings highlight the importance of vaccine literacy in increasing vaccination rates among rural patients with chronic diseases. Using the EPIS framework allowed us to reflect upon the challenges, ensure resilience during changing local contexts, and plan and implement a promising, cost-effective intervention in rural areas.

CONCLUSIONS: This study provides insights into the need for tailored educational interventions based on disease status, which has implications for public health and patient care in rural and underserved communities. Academic-community partnerships can be useful for successful knowledge transfer for vaccine acceptance to reduce rural health disparities.}, } @article {pmid38248372, year = {2024}, author = {Bota, AV and Bratosin, F and Bogdan, I and Septimiu-Radu, S and Ilie, AC and Burtic, SR and Razvan, DV and Tudor, R and Indries, MF and Csep, AN and Fildan, AP and Budea, CM and Marincu, I}, title = {Assessing the Quality of Life, Coping Strategies, Anxiety and Depression Levels in Patients with Long-COVID-19 Syndrome: A Six-Month Follow-Up Study.}, journal = {Diseases (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {38248372}, issn = {2079-9721}, abstract = {This longitudinal study investigates the psychosocial effects of long-COVID Syndrome, a domain still not extensively researched. It specifically evaluates the quality of life, coping mechanisms, anxiety and depression levels in COVID-19 survivors, differentiating between those with and without long-COVID Syndrome. Conducted at the Victor Babes Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania, the study utilized a cohort of patients diagnosed with mild to moderate COVID-19. The following standardized tools: WHOQOL-BREF for quality of life, COPE-60 for coping strategies, and the Hospital Anxiety and Depression Scale (HADS), were employed for the assessment. The sample consisted of 86 patients displaying persistent post-acute symptoms and 432 asymptomatic patients at the 6-month post-discharge mark. Patients with frequent post-acute symptoms reported significantly higher levels of fatigue (8.2 ± 1.4), cognitive difficulties (7.5 ± 1.6), and respiratory challenges (7.8 ± 1.3), along with a markedly lower overall quality of life (7.0 ± 1.5) compared to their asymptomatic counterparts. HADS scores revealed elevated depression (6.8 ± 1.9) and anxiety (7.1 ± 2.3) in the symptomatic group. Quality of life, as evaluated through the use of WHOQOL-BREF, showed lower scores in the symptomatic cohort across physical (58.8 ± 15.8), mental (56.3 ± 16.4), and social domains (50.2 ± 17.5). COPE-60 findings indicated a higher prevalence of disengagement (56.4%) and emotion-focused coping strategies (61.8%) in the symptomatic group, in contrast to 30.1% and 37.0%, respectively, in the asymptomatic group. The study highlights that long-COVID Syndrome significantly deteriorates the quality of life and is associated with increased depression and anxiety levels. The prevalent use of disengagement and emotion-focused coping strategies among patients with persistent symptoms suggests a need for enhanced psychosocial support tailored to this subgroup.}, } @article {pmid38248331, year = {2024}, author = {Vaivode, K and Saksis, R and Litvina, HD and Niedra, H and Spriņģe, ML and Krūmiņa, U and Kloviņš, J and Rovite, V}, title = {Single-Cell RNA Sequencing Reveals Alterations in Patient Immune Cells with Pulmonary Long COVID-19 Complications.}, journal = {Current issues in molecular biology}, volume = {46}, number = {1}, pages = {461-468}, pmid = {38248331}, issn = {1467-3045}, support = {1.1.1.1/21/A/029//European Regional Development Fund (ERDF)/ ; }, abstract = {Since the emergence of the COVID-19 pandemic, the effects of SARS-CoV-2 have been extensively researched. While much is already known about the acute phase of the infection, increasing attention has turned to the prolonged symptoms experienced by a subset of individuals, commonly referred to as long COVID-19 patients. This study aims to delve deeper into the immune landscape of patients with prolonged symptoms by implementing single-cell mRNA analysis. A 71-year-old COVID-19 patient presenting with persistent viral pneumonia was recruited, and peripheral blood samples were taken at 3 and 2 years post-acute infection onset. Patients and control peripheral blood mononuclear cells (PBMCs) were isolated and single-cell sequenced. Immune cell population identification was carried out using the ScType script. Three months post-COVID-19 patients' PBMCs contained a significantly larger immature neutrophil population compared to 2-year and control samples. However, the neutrophil balance shifted towards a more mature profile after 18 months. In addition, a notable increase in the CD8+ NKT-like cells could be observed in the 3-month patient sample as compared to the later one and control. The subsequent change in these cell populations over time may be an indicator of an ongoing failure to clear the SARS-CoV-2 infection and, thus, lead to chronic COVID-19 complications.}, } @article {pmid38248288, year = {2024}, author = {Rudroff, T}, title = {Artificial Intelligence's Transformative Role in Illuminating Brain Function in Long COVID Patients Using PET/FDG.}, journal = {Brain sciences}, volume = {14}, number = {1}, pages = {}, pmid = {38248288}, issn = {2076-3425}, abstract = {Cutting-edge brain imaging techniques, particularly positron emission tomography with Fluorodeoxyglucose (PET/FDG), are being used in conjunction with Artificial Intelligence (AI) to shed light on the neurological symptoms associated with Long COVID. AI, particularly deep learning algorithms such as convolutional neural networks (CNN) and generative adversarial networks (GAN), plays a transformative role in analyzing PET scans, identifying subtle metabolic changes, and offering a more comprehensive understanding of Long COVID's impact on the brain. It aids in early detection of abnormal brain metabolism patterns, enabling personalized treatment plans. Moreover, AI assists in predicting the progression of neurological symptoms, refining patient care, and accelerating Long COVID research. It can uncover new insights, identify biomarkers, and streamline drug discovery. Additionally, the application of AI extends to non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), which have shown promise in alleviating Long COVID symptoms. AI can optimize treatment protocols by analyzing neuroimaging data, predicting individual responses, and automating adjustments in real time. While the potential benefits are vast, ethical considerations and data privacy must be rigorously addressed. The synergy of AI and PET scans in Long COVID research offers hope in understanding and mitigating the complexities of this condition.}, } @article {pmid38247666, year = {2023}, author = {Marques, FRDM and Laranjeira, C and Carreira, L and Gallo, AM and Baccon, WC and Paiano, M and Baldissera, VDA and Salci, MA}, title = {Illness Experiences of Brazilian People Who Were Hospitalized Due to COVID-19 and Faced Long COVID Repercussions in Their Daily Life: A Constructivist Grounded Theory Study.}, journal = {Behavioral sciences (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {38247666}, issn = {2076-328X}, support = {This work was supported by FCT-Fundação para a Ciência e a Tecnologia, I.P. (UIDB/05704/2020 and UIDP/05704/2020) and by the Scientific Employment Stimulus-Institutional Call-[CEECINST/00051/2018].//Fundação para a Ciência e Tecnologia/ ; }, abstract = {Long COVID is a multisystem condition that has multiple consequences for the physical, mental, and social health of COVID-19 survivors. The impact of the long COVID condition remains unclear, particularly among middle-aged and older adults, who are at greater risk than younger people of persisting symptoms associated with COVID-19. Therefore, we aimed to understand the experiences of middle-aged and older people who had been hospitalized for COVID-19 and the repercussions of long-term COVID symptoms in their daily lives. A qualitative study was carried out, adopting the framework of the constructivist grounded theory (CGT) proposed by Kathy Charmaz. Fifty-six middle-aged and older adult participants from the southern region of Brazil were recruited. Data were gathered from semi-structured telephone interviews. Concomitantly a comparative analysis was performed to identify categories and codes using the MaxQDA[®] software (version 2022). Three subcategories were identified: (1) experiencing COVID-19 in the acute phase; (2) oscillating between 'good days' and 'bad days' in long COVID; and (3) (re)constructing identity. These concepts interact with each other and converge upon the central category of this study: recasting oneself to the uniqueness of the illness experience of long COVID. Our findings provided insights related to the disruption in the lives of long COVID-19 sufferers who still live with persistent symptoms of the disease, including physical, social, family, emotional and spiritual repercussions. Likewise, this study may aid in developing friendly and welcoming social environments, lowering stigma and prejudice towards patients with long COVID, and fostering prompt and suitable policy support and mental health care for these individuals.}, } @article {pmid38246521, year = {2024}, author = {Daynes, E and Mills, G and Hull, JH and Bishop, NC and Bakali, M and Burtin, C and McAuley, HJC and Singh, SJ and Greening, NJ}, title = {Pulmonary Rehabilitation for People With Persistent Symptoms After COVID-19.}, journal = {Chest}, volume = {166}, number = {3}, pages = {461-471}, doi = {10.1016/j.chest.2024.01.029}, pmid = {38246521}, issn = {1931-3543}, mesh = {Humans ; *COVID-19/rehabilitation/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Exercise Therapy/methods ; }, abstract = {TOPIC IMPORTANCE: COVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary rehabilitation is a key treatment for adults with chronic respiratory diseases, with the aims to improve symptom management and increase functional capacity. Given the similarities in presentation and aims, a pulmonary rehabilitation program may be optimal to meet the needs of those with ongoing symptoms after COVID-19.

REVIEW FINDINGS: Aerobic and strength training has shown benefit for adults living with long COVID, although there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with long COVID, and considerations on treatment before rehabilitation, or alongside rehabilitation, are necessary. Considerations on postexertional malaise are important in this population, and evidence from the chronic fatigue syndrome literature supports the need for individualization of exercise programs, and considerations for those who have an adverse reaction to activity and/or exercise.

SUMMARY: This narrative review summarizes the current evidence on pulmonary rehabilitation programs in a long-COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programs in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanisms for immunology improvement, and management of breathing pattern disorders in these programs.}, } @article {pmid38245110, year = {2024}, author = {Müller, SA and Isaaka, L and Mumm, R and Scheidt-Nave, C and Heldt, K and Schuster, A and Abdulaziz, M and El-Bcheraoui, C and Hanefeld, J and Agweyu, A}, title = {Latent viral infections as neglected risk factors for long COVID - Authors' reply.}, journal = {The Lancet. Global health}, volume = {12}, number = {2}, pages = {e198}, doi = {10.1016/S2214-109X(23)00595-8}, pmid = {38245110}, issn = {2214-109X}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Virus Diseases ; Risk Factors ; *Nervous System Diseases ; }, } @article {pmid38245109, year = {2024}, author = {Abdoli, A and Taghipour, A and Jahromi, MAM and Eftekharian, F and Sahraei, R and Sanie, MS}, title = {Latent viral infections as neglected risk factors for long COVID.}, journal = {The Lancet. Global health}, volume = {12}, number = {2}, pages = {e197}, doi = {10.1016/S2214-109X(24)00010-X}, pmid = {38245109}, issn = {2214-109X}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Risk Factors ; *Nervous System Diseases ; }, } @article {pmid38244204, year = {2024}, author = {Halasz, G and Di Spigno, F and Donelli, D and Giacani, A and Moderato, L and Lazzeroni, D and De Luca, L and Piepoli, M}, title = {Cardiopulmonary limitations in young Long Covid patients: A case control study.}, journal = {European journal of preventive cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjpc/zwae029}, pmid = {38244204}, issn = {2047-4881}, } @article {pmid38243748, year = {2024}, author = {Castriotta, L and Onder, G and Rosolen, V and Beorchia, Y and Fanizza, C and Bellini, B and Floridia, M and Giuliano, M and Silenzi, A and Pricci, F and Grisetti, T and Grassi, T and Tiple, D and Villa, M and Profili, F and Francesconi, P and Barbone, F and Bisceglia, L and Brusaferro, S}, title = {Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection.}, journal = {European journal of public health}, volume = {34}, number = {3}, pages = {592-599}, pmid = {38243748}, issn = {1464-360X}, support = {//National Centre for Diseases Prevention and Control/ ; //Italian Ministry of Health/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Retrospective Studies ; Female ; Middle Aged ; Aged ; Adult ; *Hospitalization/statistics & numerical data ; Italy/epidemiology ; *SARS-CoV-2 ; *Patient Acceptance of Health Care/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Health Resources/statistics & numerical data ; Intensive Care Units/statistics & numerical data ; }, abstract = {BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID.

METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions.

RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38).

CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.}, } @article {pmid38243329, year = {2024}, author = {Haischer, MH and Opielinski, LE and Mirkes, LM and Uhrich, TD and Bollaert, RE and Danduran, M and Bement, MH and Piacentine, LB and Papanek, PE and Hunter, SK}, title = {Heart rate variability is reduced in COVID-19 survivors and associated with physical activity and fatigue.}, journal = {Physiological reports}, volume = {12}, number = {2}, pages = {e15912}, pmid = {38243329}, issn = {2051-817X}, support = {N/A//Institute for Women's Leadership at Marquette University/ ; }, mesh = {Humans ; Heart Rate/physiology ; *COVID-19 ; Exercise/physiology ; Fatigue ; Survivors ; }, abstract = {Reduced heart rate variability (HRV) and fatigue are common after COVID-19 infection and both are potentially influenced by physical activity (PA). We compared resting HRV, PA from accelerometers and questionnaires, and self-reported fatigue in 41 COVID-19 survivors (~8 months postinfection, 38 ± 17 years) with 41 matched controls. Differences in HRV were observed on acceleration capacity (p = 0.041), deceleration capacity (p = 0.032), high-frequency peak frequency (p = 0.019), absolute low-frequency power (p = 0.042), relative very low-frequency power (p = 0.012), SD2 (from Poincare plot; p = 0.047), and DFA2 (slope of long-term detrended fluctuation analysis; p = 0.004). Fatigue was greater in COVID-19 survivors (p < 0.001) with no differences in PA. Moderate-vigorous physical activity (MVPA) (Standardized Beta = -0.427, p = 0.003) and steps per day (Standardized Beta = -0.402, p = 0.007) were associated with DFA2 in COVID-19 survivors after controlling for age, sex, and body fat percentage. Fatigue was correlated to less MVPA (Spearman's rho = 0.342, p = 0.031) and fewer steps per day (rho = 0.329, p = 0.038) in COVID-19 survivors, and was indirectly linked to HRV through these PA mediators (Estimate = -0.20; p = 0.040). We present a model showing the complex relations between HRV, PA, and fatigue that provides the foundation for strategies to improve outcomes and rehabilitation after COVID-19 infection.}, } @article {pmid38242707, year = {2023}, author = {Beneš, J}, title = {Pathogenesis of infections caused by SARS-CoV-2.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {72}, number = {4}, pages = {221-238}, pmid = {38242707}, issn = {1210-7913}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 primarily causes mucosal infections of the respiratory or intestinal tract. This virus, unlike other viruses responsible for similar mucosal infections, is characterized by an extraordinary ability to modify the immune response at several levels and thus cause a range of clinical complications. These manipulations create a false picture of pyogenic bacterial infection. The course of the disease is mainly determined by the natural mucosal immunity which can stop the virus from multiplying in the early stages of infection before it can exert its influence. COVID-19 has two main clinical forms: mucosal infection (respiratory or intestinal) and pneumonia. Pneumonia is associated with activation of the vascular endothelium and a procoagulant state. Viremia does not belong to the standard course of the disease. Affecting organs other than the lungs - whether during an active infection or later (long covid) - is usually caused by immunopathological reactions or hormonal regulation disorders.}, } @article {pmid38242110, year = {2024}, author = {Weihrauch, S and Winkler, T}, title = {[Long-Covid: On the Genealogy of a New Disease and a Chance of a Cultural Sociological (Research) Perspective].}, journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))}, volume = {86}, number = {1}, pages = {37-42}, doi = {10.1055/a-2191-2025}, pmid = {38242110}, issn = {1439-4421}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Germany ; }, abstract = {The article deals with the question of how Long Covid has become a disease. Of interest are the pathways and imprints, how the problem has established itself as a disease and materialized, or how society has come to the realization of its problems. Far-reaching institutionalization of Long Covid as a disease belies existing interpretive struggles in and around Long-Covid. How meaning is produced and how it becomes effective might be the starting point of a praxeological cultural analysis as proposed here.}, } @article {pmid38241342, year = {2024}, author = {Fan, Y and Liang, X}, title = {Causal relationship between COVID-19 and chronic pain: A mendelian randomization study.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0295982}, pmid = {38241342}, issn = {1932-6203}, mesh = {Humans ; *Chronic Pain/complications/epidemiology/genetics ; Post-Acute COVID-19 Syndrome ; Mendelian Randomization Analysis ; *COVID-19/epidemiology ; Causality ; Genome-Wide Association Study ; }, abstract = {OBJECTIVE: COVID-19 is a highly transmissible disease that can result in long-term symptoms, including chronic pain. However, the mechanisms behind the persistence of long-COVID pain are not yet fully elucidated, highlighting the need for further research to establish causality. Mendelian randomization (MR), a statistical technique for determining a causal relationship between exposure and outcome, has been employed in this study to investigate the association between COVID-19 and chronic pain.

MATERIAL AND METHODS: The IVW, MR Egger, and weighted median methods were employed. Heterogeneity was evaluated using Cochran's Q statistic. MR Egger intercept and MR-PRESSO tests were performed to detect pleiotropy. The Bonferroni method was employed for the correction of multiple testing. R software was used for all statistical analyses.

RESULT: Based on the IVW method, hospitalized COVID-19 patients exhibit a higher risk of experiencing lower leg joint pain compared to the normal population. Meanwhile, the associations between COVID-19 hospitalization and back pain, headache, and pain all over the body were suggestive. Additionally, COVID-19 patients requiring hospitalization were found to have a suggestive higher risk of experiencing neck or shoulder pain and pain all over the body compared to those who did not require hospitalization. Patients with severe respiratory-confirmed COVID-19 showed a suggestive increased risk of experiencing pain all over the body compared to the normal population.

CONCLUSION: Our study highlights the link between COVID-19 severity and pain in different body regions, with implications for targeted interventions to reduce COVID-19 induced chronic pain burden.}, } @article {pmid38241071, year = {2024}, author = {Pires, L and Reis, C and Mesquita Facão, AR and Moniri, A and Marreiros, A and Drummond, M and Berger-Estilita, J}, title = {Fatigue and Mental Illness Symptoms in Long COVID: Protocol for a Prospective Cohort Multicenter Observational Study.}, journal = {JMIR research protocols}, volume = {13}, number = {}, pages = {e51820}, pmid = {38241071}, issn = {1929-0748}, abstract = {BACKGROUND: The aftermath of the COVID-19 pandemic continues to affect millions worldwide, resulting in persisting postvirus complaints and impacting peoples' quality of life. Long COVID, characterized by lingering symptoms like fatigue and mental illness, can extend beyond a few months, necessitating further research to understand its implications.

OBJECTIVE: This study aims to quantify the degree of physical and psychological fatigue in patients following COVID-19 infection and examine its correlation with mental health disorders.

METHODS: Using a consecutive nonrandom sampling technique, we will conduct a prospective cohort multicenter observational study in 5 Portuguese hospitals. Symptomatic adult patients with previous COVID-19 attending follow-up consultations will be enrolled. We will include patients who had mild, moderate, and severe acute disease. We will assess clinical outcomes related to COVID-19, including the type of respiratory support such as high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation. The exclusion criteria will include previous severe psychiatric disorders confirmed by a psychiatrist; refusal or inability to respond to the questionnaire; concomitant neurological disorder; persistent fatigue symptoms during the 6 months before infection; and the need for invasive mechanical ventilation during COVID-19 infection due to a high prevalence of postintensive care syndrome. Our primary outcome is the prevalence of fatigue in patients with post-COVID-19 depression and/or anxiety, as measured by the Chalder Fatigue Scale (CFQ-11) and the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes will include an assessment of health-related quality of life via the EQ-5D questionnaire and an exploration of the prevalence of symptoms of posttraumatic stress disorder (PTSD) using the 14-item Posttraumatic Stress Scale (PTSS-14). We will also examine the association between mental health symptoms and the severity of acute COVID-19. The post-COVID-19 data will be collected at least 6 months after the positive test and no longer than 9 months during the clinical appointment.

RESULTS: We expect our multicenter study on patients post COVID-19 to reveal a significant link between mental illness symptoms and both physical and psychological fatigue. Patients with heightened depression and anxiety may report increased levels of fatigue. Additionally, we expect to find persistent PTSD symptoms in a subset of participants, indicating the enduring psychological impact of the virus.

CONCLUSIONS: This study may underscore the need for integrated care addressing physical and mental health in patients post COVID-19. The observed connections emphasize the importance of considering mental well-being for long-term health outcomes. Despite study limitations, our findings contribute valuable insights for future treatment strategies and highlight the necessity for comprehensive mental health support in post-COVID-19 care. This research provides valuable insights into the mental health implications of COVID-19 and its impact on post-COVID-19 fatigue and the overall well-being of affected individuals.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05323318; https://clinicaltrials.gov/study/NCT05323318.

DERR1-10.2196/51820.}, } @article {pmid38240001, year = {2024}, author = {Tsuchida, T and Ishibashi, Y and Inoue, Y and Ishizuka, K and Katayama, K and Hirose, M and Nakagama, Y and Kido, Y and Akashi, Y and Otsubo, T and Matsuda, T and Ohira, Y}, title = {Treatment of long COVID complicated by postural orthostatic tachycardia syndrome-Case series research.}, journal = {Journal of general and family medicine}, volume = {25}, number = {1}, pages = {53-61}, pmid = {38240001}, issn = {2189-7948}, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS.

METHODS: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits.

RESULTS: Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to β-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements.

CONCLUSIONS: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.}, } @article {pmid38238626, year = {2024}, author = {Naddaf, M}, title = {Long-COVID signatures identified in huge analysis of blood proteins.}, journal = {Nature}, volume = {626}, number = {7997}, pages = {19-20}, pmid = {38238626}, issn = {1476-4687}, mesh = {Humans ; Blood Proteins/analysis/immunology/metabolism ; *Post-Acute COVID-19 Syndrome/blood/immunology/physiopathology ; }, } @article {pmid38237987, year = {2024}, author = {Zaidi, AK}, title = {Future insights.}, journal = {Progress in molecular biology and translational science}, volume = {202}, number = {}, pages = {219-223}, doi = {10.1016/bs.pmbts.2023.11.004}, pmid = {38237987}, issn = {1878-0814}, mesh = {Humans ; *Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Public Health ; Vaccination ; }, abstract = {This chapter explores two significant aspects of the ongoing COVID-19 pandemic: the realistic prediction of its end and the status of long-term COVID in 2023. While the World Health Organization (WHO) declared an end to COVID-19 as a public health emergency, the possibility of future waves caused by variants remains. Widespread vaccination and prior infections provide substantial protection, but the virus is expected to persist, necessitating continued monitoring and potential reimplementation of control measures. Long-term COVID, characterized by persistent or new symptoms after the acute phase, remains a concern. Recent findings suggest a reduced risk of prolonged COVID with initial Omicron variants. However, targeted treatments are lacking, and current approaches rely on symptomatic and supportive care. Psychological support and multidisciplinary interventions are essential. Comprehensive studies, standardized criteria, and international registries are needed to advance research and develop effective therapies. Understanding these uncertainties will guide us towards effectively managing the pandemic and providing optimal care for long COVID patients.}, } @article {pmid38237983, year = {2024}, author = {Zaidi, AK and Dehgani-Mobaraki, P}, title = {Long Covid.}, journal = {Progress in molecular biology and translational science}, volume = {202}, number = {}, pages = {113-125}, doi = {10.1016/bs.pmbts.2023.11.002}, pmid = {38237983}, issn = {1878-0814}, mesh = {Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; SARS-CoV-2 ; }, abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID. Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children. The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored. Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.}, } @article {pmid38237090, year = {2024}, author = {Hayward, W and Buch, ER and Norato, G and Iwane, F and Dash, D and Salamanca-Girón, RF and Bartrum, E and Walitt, B and Nath, A and Cohen, LG}, title = {Procedural Motor Memory Deficits in Patients With Long-COVID.}, journal = {Neurology}, volume = {102}, number = {3}, pages = {e208073}, pmid = {38237090}, issn = {1526-632X}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Aged ; Aged, 80 and over ; Male ; *Psychomotor Performance ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Cross-Sectional Studies ; Pandemics ; Prospective Studies ; *COVID-19 ; Motor Skills ; Memory Disorders/etiology ; }, abstract = {BACKGROUND AND OBJECTIVES: At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms ("Long-COVID") including "brain fog" and deficits in declarative memory. It is not known if Long-COVID affects patients' ability to form and retain procedural motor skill memories. The objective was to determine the ability of patients with Long-COVID to acquire and consolidate a new procedural motor skill over 2 training days. The primary outcome was to determine difference in early learning, measured as the increase in correct sequence typing speed over the initial 11 practice trials of a new skill. The secondary outcomes were initial and final typing speed on days 1 and 2, learning rate, overnight consolidation, and typing accuracy.

METHODS: In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days (NCT05746624). Patients with Long-COVID (reporting persistent post-coronavirus disease 2019 [COVID-19] symptoms for more than 4 weeks) were recruited at the NIH. Patients were matched one-to-one by age and sex to controls recruited during the pandemic using a crowd-sourcing platform. Selection criteria included age 18-90 years, English speaking, right-handed, able to type with the left hand, denied active fever or respiratory infection, and no previous task exposure. Data were also compared with an age-matched and sex-matched control group who performed the task online before the COVID-19 pandemic (prepandemic controls).

RESULTS: In total, 105 of 236 patients contacted agreed to participate and completed the experiment (mean ± SD age 46 ± 12.8 years, 82% female). Both healthy control groups had 105 participants (mean age 46 ± 13.1 and 46 ± 11.9 years, 82% female). Early learning was comparable across groups (Long-COVID: 0.36 ± 0.24 correct sequences/second, pandemic controls: 0.36 ± 0.53 prepandemic controls: 0.38 ± 0.57, patients vs pandemic controls [CI -0.068 to 0.067], vs prepandemic controls [CI -0.084 to 0.052], and between controls [CI -0.083 to 0.053], p = 0.82). Initial and final typing speeds on days 1 and 2 were slower in patients than controls. Patients with Long-COVID showed a significantly reduced overnight consolidation and a nonsignificant trend to reduced learning rates.

DISCUSSION: Early learning was comparable in patients with Long-COVID and controls. Anomalous initial performance is consistent with executive dysfunction. Reduction in overnight consolidation may relate to deficits in procedural memory formation.}, } @article {pmid38236985, year = {2024}, author = {Ruf, W}, title = {Immune damage in Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6680}, pages = {262-263}, doi = {10.1126/science.adn1077}, pmid = {38236985}, issn = {1095-9203}, mesh = {Humans ; *Blood Coagulation/immunology ; *Complement System Proteins/analysis/immunology ; *Post-Acute COVID-19 Syndrome/blood/immunology ; }, abstract = {Links between the complement and coagulation systems could lead to Long Covid therapies.}, } @article {pmid38236961, year = {2024}, author = {Cervia-Hasler, C and Brüningk, SC and Hoch, T and Fan, B and Muzio, G and Thompson, RC and Ceglarek, L and Meledin, R and Westermann, P and Emmenegger, M and Taeschler, P and Zurbuchen, Y and Pons, M and Menges, D and Ballouz, T and Cervia-Hasler, S and Adamo, S and Merad, M and Charney, AW and Puhan, M and Brodin, P and Nilsson, J and Aguzzi, A and Raeber, ME and Messner, CB and Beckmann, ND and Borgwardt, K and Boyman, O}, title = {Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {383}, number = {6680}, pages = {eadg7942}, doi = {10.1126/science.adg7942}, pmid = {38236961}, issn = {1095-9203}, mesh = {Humans ; *Complement Activation ; *Complement System Proteins/analysis/metabolism ; *Post-Acute COVID-19 Syndrome/blood/complications/immunology ; *Thromboinflammation/blood/immunology ; Biomarkers/blood ; *Proteome ; Proteomics ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; }, abstract = {Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.}, } @article {pmid38235145, year = {2023}, author = {Cezar, R and Kundura, L and André, S and Lozano, C and Vincent, T and Muller, L and Lefrant, JY and Roger, C and Claret, PG and Duvnjak, S and Loubet, P and Sotto, A and Tran, TA and Estaquier, J and Corbeau, P}, title = {T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1335352}, pmid = {38235145}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Leukocytes, Mononuclear ; SARS-CoV-2 ; Apoptosis ; Cytokines ; Disease Progression ; }, abstract = {BACKGROUND: As about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.

METHOD: To this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex[®], quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.

RESULTS: None of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).

CONCLUSIONS: Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.}, } @article {pmid38235010, year = {2023}, author = {Shibafar, S and Jafarlou, F}, title = {A review on the impacts of COVID-19 on the auditory system: Implications for public health promotion research.}, journal = {Health promotion perspectives}, volume = {13}, number = {4}, pages = {280-289}, pmid = {38235010}, issn = {2228-6497}, abstract = {BACKGROUND: Currently, there are few studies on the relationship between COVID-19 and the auditory system. In the current study, a review of the studies conducted in the fields of etiopathology, clinical manifestations, research, and treatment of hearing loss caused byCOVID-19 was conducted, which can be used as a baseline for future studies.

METHODS: We utilized the research approach suggested by Arksey and O'Malley to carry out this scoping review. Search was conducted in Farsi and English with a focus on the onset of hearing loss in patients with COVID-19 through Medline and PubMed, and Google Scholar search engine. Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss, ear pain, ear discharge, and otitis media. Studies were eligible for inclusion if there was a description of the otologic dysfunction, specifically onset, duration, or clinical outcomes.

RESULTS: Among 90 studies identified, 35 studies were included in the review process. Our findings suggest several possible mechanisms for sudden sensorineural hearing loss (SSNHL) in COVID-19 patients, and COVID-19 infection could have deleterious effects on the inner ear, specifically on the hair cells of the cochlea despite patients being asymptomatic and early identification of SSNHL in COVID-19patients can save the hearing and also patient.

CONCLUSION: Hearing loss in COVID-19 infection has not received much attention by health care professionals. Sensorineural hearing loss (SNHL), tinnitus, and/or vertigo have been shown to occur during and following COVID-19 infection. Due to lack of research studies, and the inconsistency and even contradictory of the findings, it remains questionable whether COVID-19 contributes to the high incidence of hearing loss. The proper understanding of the mechanisms behind hearing loss in COVID-19 infections needs further research. However, it seems likely that SNHL could be included among the manifestations of those-called "long COVID" syndrome.}, } @article {pmid38234859, year = {2023}, author = {Quan, SF and Weaver, MD and Czeisler, MÉ and Barger, LK and Booker, LA and Howard, ME and Jackson, ML and Lane, RI and McDonald, CF and Ridgers, A and Robbins, R and Varma, P and Wiley, JF and Rajaratnam, SMW and Czeisler, CA}, title = {Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 infection (PASC).}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38234859}, support = {K01 HL150339/HL/NHLBI NIH HHS/United States ; R01 OH011773/OH/NIOSH CDC HHS/United States ; R01OH011773/ACL/ACL HHS/United States ; R56 HL151637/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Obstructive sleep apnea (OSA) is associated with COVID-19 infection. Fewer investigations have assessed OSA as a possible risk for the development of Post-Acute Sequelae of SARS-CoV-2 infection (PASC).

RESEARCH QUESTION: In a general population, is OSA associated with increased odds of PASC-related symptoms and with an overall definition of PASC?

STUDY DESIGN: Cross-sectional survey of a general population of 24,803 U.S. adults.

RESULTS: COVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence rates for a wide variety of persistent (> 3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models adjusted for demographic, anthropometric, comorbid medical and socioeconomic factors, OSA was associated with all putative PASC-related symptoms with the highest adjusted odds ratios (aOR) being fever (2.053) and nervous/anxious (1.939) respectively. Elastic net regression identified the 13 of 37 symptoms most strongly associated with COVID-19 infection. Four definitions of PASC were developed using these symptoms either weighted equally or proportionally by their regression coefficients. In all 4 logistic regression models using these definitions, OSA was associated with PASC (range of aORs: 1.934-2.071); this association was mitigated in those with treated OSA. In the best fitting overall model requiring ≥3 symptoms, PASC prevalence was 21.9%.

CONCLUSION: In a general population sample, OSA is associated with the development of PASC-related symptoms and a global definition of PASC. A PASC definition requiring the presence of 3 or more symptoms may be useful in identifying cases and for future research.}, } @article {pmid38234406, year = {2024}, author = {León-Herrera, S and Oliván-Blázquez, B and Samper-Pardo, M and Aguilar-Latorre, A and Sánchez Arizcuren, R}, title = {Motivational Interviewing as a Tool to Increase Motivation and Adherence to a Long COVID Telerehabilitation Intervention: Secondary Data Analysis from a Randomized Clinical Trial.}, journal = {Psychology research and behavior management}, volume = {17}, number = {}, pages = {157-169}, pmid = {38234406}, issn = {1179-1578}, abstract = {BACKGROUND: Although motivational interviewing was originally developed to address abuse disorders, scientific evidence confirms that it is an increasingly used and effective approach in a wide range of therapeutic interventions. To date, however, no studies have analyzed the use of this tool in patients with persistent symptoms following coronavirus disease 2019, a condition known as Long COVID.

PURPOSE: To analyze the effectiveness of motivational interviewing with regard to the adherence to telerehabilitation for Long COVID using a mobile application. As a secondary objective, factors related to greater motivation before and after the motivational interviewing techniques were analyzed.

PATIENTS AND METHODS: This longitudinal design substudy used a sample of 52 adult patients with Long COVID participating in the intervention group of a randomized clinical trial. This trial examined the effectiveness of a telerehabilitation program for this population using a mobile application. This program included three motivational interviews to achieve maximum treatment adherence. In this study, the main variables were motivation and adherence to application use. Sociodemographic and clinical data, personal constructs, and affective state were also collected. Subsequently, a descriptive, correlational, and regression statistical analysis was performed using the SPSS Statistics program.

RESULTS: The median motivation prior to the first motivational interview was 8 (IQR 2), the median at the end of the last motivational interview was 8.5 (IQR 2.75), and the change in motivation levels after the three motivational interviews was 0.5 (IQR 1). Affective state and final motivation scores were predictors of greater adherence to telerehabilitation treatment.

CONCLUSION: A high level of motivation after participating in motivational interviewing appears to be related to higher levels of adherence to telerehabilitation in patients with Long COVID. This suggests that motivational interviewing may be an effective tool in the treatment of this disease.}, } @article {pmid38233495, year = {2024}, author = {Mirza, S and Arvinden, VR and Rophina, M and Bhawalkar, J and Khan, U and Chothani, B and Singh, S and Sharma, T and Dwivedi, A and Pandey, E and Garg, S and Mukhida, SS and Sange, ZSA and Bhaumik, S and Varughese, J and Devkar, VY and Singh, J and V K, A and K, V and Mandviwala, HSH and Scaria, V and Gupta, A}, title = {Impact of COVID-19 outbreak on healthcare workers in a Tertiary Healthcare Center in India: a cross sectional study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1504}, pmid = {38233495}, issn = {2045-2322}, support = {MLP001/GenomeApp//Council of Scientific and Industrial Research (CSIR)/ ; }, mesh = {Female ; Humans ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Tertiary Care Centers ; Tertiary Healthcare ; Health Personnel ; Disease Outbreaks ; India/epidemiology ; }, abstract = {Numerous speculations have continually emerged, trying to explore the association between COVID-19 infection and a varied range of demographic and clinical factors. Frontline healthcare workers have been the primary group exposed to this infection, and there have been limited global research that examine this cohort. However, while there are a few large studies conducted on Indian healthcare professionals to investigate their potential risk and predisposing factors to COVID-19 infection, to our knowledge there are no studies evaluating the development of long COVID in this population. This cross-sectional study systematically utilized the demographic and clinical data of 3329 healthcare workers (HCW) from a tertiary hospital in India to gain significant insights into the associations between disease prevalence, severity of SARS-Cov-2 infection and long COVID. Most of the study population was found to be vaccinated (2,615, 78.5%), while 654 (19.65%) HCWs were found to be SARS-CoV-2 positive at least once. Of the infected HCWs, 75.1% (491) did not require hospitalization, whereas the rest were hospitalized for an average duration of 9 days. A total of 206 (6.19%) individuals were found to be suffering from long COVID. Persistent weakness/tiredness was the most experienced long-COVID symptom, while females (1.79, 1.25-2.57), individuals who consumed alcohol (1.85, 1.3-2.64) or had blood group B (1.9, 1.33-2.7) were at a significantly higher risk for developing long COVID.}, } @article {pmid38233059, year = {2024}, author = {Rofail, D and Somersan-Karakaya, S and Choi, JY and Przydzial, K and Zhao, Y and Hussein, M and Norton, TD and Podolanczuk, AJ and Mylonakis, E and Geba, GP}, title = {Thematic analysis to explore patients' experiences with long COVID-19: a conceptual model of symptoms and impacts on daily lives.}, journal = {BMJ open}, volume = {14}, number = {1}, pages = {e076992}, pmid = {38233059}, issn = {2044-6055}, mesh = {Adult ; Humans ; Female ; Male ; *Quality of Life/psychology ; Post-Acute COVID-19 Syndrome ; Activities of Daily Living ; Prospective Studies ; *COVID-19 ; Qualitative Research ; }, abstract = {OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life.

SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews.

PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed.

Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model.

RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months.

CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.}, } @article {pmid38232699, year = {2024}, author = {Vu, LT and Ahmed, F and Zhu, H and Iu, DSH and Fogarty, EA and Kwak, Y and Chen, W and Franconi, CJ and Munn, PR and Tate, AE and Levine, SM and Stevens, J and Mao, X and Shungu, DC and Moore, GE and Keller, BA and Hanson, MR and Grenier, JK and Grimson, A}, title = {Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.}, journal = {Cell reports. Medicine}, volume = {5}, number = {1}, pages = {101373}, pmid = {38232699}, issn = {2666-3791}, support = {U54 AI178855/AI/NIAID NIH HHS/United States ; U54 NS105541/NS/NINDS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/genetics/diagnosis ; Exercise/physiology ; Gene Expression Profiling ; Transcriptome ; Monocytes ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.}, } @article {pmid38231397, year = {2024}, author = {Sauer, MC and Barlow, PB and Comellas, AP and Garg, A}, title = {Anxiety and depression symptoms among patients with long COVID: a retrospective cohort study.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1879-1886}, pmid = {38231397}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/psychology/complications ; Male ; Female ; Middle Aged ; Retrospective Studies ; Aged ; *Depression/epidemiology ; Adult ; *Anxiety/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Anxiety Disorders/epidemiology ; }, abstract = {Patients suffering from post-acute sequelae of COVID-19 (PASC) have a higher prevalence of anxiety and depression than the general population. The long-term trajectory of these sequelae is still unfolding. To assess the burden of anxiety and depression among patients presenting to the University of Iowa Hospitals and Clinics (UIHC) post-COVID-19 clinic, we analyzed how patient factors influenced Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scores. In this retrospective cohort study, the GAD-7 and PHQ-9 questionnaire scores of patients presenting to the UIHC post-COVID clinic between March 2021-February 2022 (N = 455) were compared to the scores of a sample of patients presenting to the general internal medicine (GIM) clinic during the same period (N = 94). Our analysis showed that patients with an absent history of depression on their electronic medical record (EMR) problem list scored significantly higher on the GAD-7 (mean difference -1.62, 95% CI -3.12 to -0.12, p = 0.034) and PHQ-9 (mean difference -4.45, 95% CI -5.53 to -3.37, p < 0.001) questionnaires compared to their similar counterparts in the GIM clinic. On the other hand, patients with an absent history of anxiety on their EMR problem list scored significantly higher on the GAD-7 (mean difference -2.90, 95% CI -4.0 to -1.80, p < 0.001) but not on the PHQ-9 questionnaire (p = 0.196). Overall, patients with PASC may have experienced a heavier burden of newly manifest anxiety and depression symptoms compared to patients seen in the GIM clinic. This suggests that the mental health impacts of PASC may be more pronounced in patients with no prior history of anxiety or depression.}, } @article {pmid38231284, year = {2024}, author = {Torki, E and Hoseininasab, F and Moradi, M and Sami, R and Sullman, MJM and Fouladseresht, H}, title = {The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case-control study.}, journal = {Clinical and experimental medicine}, volume = {24}, number = {1}, pages = {1}, pmid = {38231284}, issn = {1591-9528}, support = {3400839//Isfahan University of Medical Sciences/ ; 3400839//Isfahan University of Medical Sciences/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Case-Control Studies ; Interleukin-6/genetics ; C-Reactive Protein ; Demography ; HLA-A Antigens ; }, abstract = {Long Covid-19 syndrome (LCS) manifests with a wide range of clinical symptoms, yet the factors associated with LCS remain poorly understood. The current study aimed to investigate the relationships that demographic characteristics, clinical history, laboratory indicators, and the frequency of HLA-I alleles have with the likelihood of developing LCS. We extracted the demographic characteristics and clinical histories from the medical records of 88 LCS cases (LCS[+] group) and 96 individuals without LCS (LCS[-] group). Furthermore, we evaluated the clinical symptoms, serum levels of interleukin (IL)-6 and tumor necrosis factor-α, laboratory parameters, and the frequencies of HLA-I alleles. Following this we used multiple logistic regression to investigate the association these variables had with LCS. Subjects in the LCS[+] group were more likely to have experienced severe Covid-19 symptoms and had higher body mass index (BMI), white blood cell, lymphocyte counts, C-reactive protein (CRP), and IL-6 levels than those in the LCS[-] group (for all: P < 0.05). Moreover, the frequencies of the HLA-A*11, -B*14, -B*38, -B*50, and -C*07 alleles were higher in the LCS[+] group (for all: P < 0.05). After adjusting for the most important variables, the likelihood of suffering from LCS was significantly associated with BMI, CRP, IL-6, the HLA-A*11, and -C*07 alleles, as well as a positive history of severe Covid-19 (for all: P < 0.05). Our study showed that a history of severe Covid-19 during the acute phase of the disease, the HLA-A*11, and -C*07 alleles, higher BMI, as well as elevated serum CRP and IL-6 levels, were all associated with an increased likelihood of LCS.}, } @article {pmid38229877, year = {2024}, author = {Taquet, M and Skorniewska, Z and Zetterberg, H and Geddes, JR and Mummery, CJ and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Raman, B and Leavy, OC and Richardson, M and Elneima, O and McAuley, HJC and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Houchen-Wolloff, L and Mansoori, P and Greening, NJ and Harrison, EM and Docherty, AB and Lone, NI and Quint, J and Greenhalf, W and Wain, LV and Brightling, CE and Evans, RE and Harrison, PJ and Koychev, I and , }, title = {Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.}, journal = {Brain communications}, volume = {6}, number = {1}, pages = {fcad357}, pmid = {38229877}, issn = {2632-1297}, support = {CH/F/21/90010/BHF_/British Heart Foundation/United Kingdom ; G0600475/MRC_/Medical Research Council/United Kingdom ; G1001128/MRC_/Medical Research Council/United Kingdom ; MCCC-RP-14-A17178/MCCC_/Marie Curie/United Kingdom ; }, abstract = {A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.}, } @article {pmid38229792, year = {2023}, author = {Leahy, J and Bajracharya, R and Altonen, B and Ferreira-Ortiz, M and Silvera, L and Astua, AJ}, title = {Post-discharge Healthcare Usage and Costs From March 2020 Through the Omicron Surge for Individuals Hospitalized With COVID-19.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50663}, pmid = {38229792}, issn = {2168-8184}, abstract = {INTRODUCTION: Despite the rise of post-COVID care centers, few studies exist that quantify the burden of patient healthcare usage and hospital costs after COVID-19 hospitalization. It is essential to target post-COVID follow-up care to the individuals who need it most, such that costs and emergencies are minimized and health and appointment attendance are optimized.

METHODS: This was a retrospective cohort comparison among four groups of 50 patients (200 total). Post-discharge healthcare utilization metrics were collected for individuals hospitalized with COVID-19 during the first four surges of the pandemic to compare how patients receive and seek care in the year after they contract COVID-19. A brief cost analysis was done to identify high-usage groups that could be targeted for intervention to decrease post-COVID hospitalization emergencies and burden.

RESULTS: Patients hospitalized during the Omicron surge were scheduled for the most specialist visits on average, significantly higher than average specialist visits in the Delta surge (p<0.05). The Delta surge had significantly less specialty care and missed visits than all other surges (p<0.05) and less primary care than the first two surges of the pandemic (p<0.05). Patients with type 2 diabetes and asthma had the highest overall costs (p<0.05). Females and Hispanic patients had the highest specialty and ED costs (p<0.05).

CONCLUSION: Each surge reflects a different approach to post-COVID care, with the Omicron surge demonstrating the heaviest usage overall, particularly with specialty visits. Increased specialty referrals may exacerbate rates of missed appointments, while primary care may lower emergency visits. Future approaches to post-COVID care design should identify patients at risk for emergencies and reinstate them with primary care.}, } @article {pmid38229583, year = {2024}, author = {Devine, K and Russell, CD and Blanco, GR and Walker, BR and Homer, NZM and Denham, SG and Simpson, JP and Leavy, OC and Elneima, O and McAuley, HJC and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Houchen-Wolloff, L and Greening, NJ and Lone, NI and Thorpe, M and Greenhalf, W and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Raman, B and Moore, SC and Dunning, J and Semple, MG and Andrew, R and Wain, LV and Evans, RA and Brightling, CE and Kenneth Baillie, J and Reynolds, RM and , }, title = {Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.}, journal = {Clinical endocrinology}, volume = {100}, number = {4}, pages = {317-327}, doi = {10.1111/cen.15012}, pmid = {38229583}, issn = {1365-2265}, support = {MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Male ; Female ; *COVID-19 ; Hydrocortisone ; Acute Disease ; Aftercare ; Patient Discharge ; Glucocorticoids/therapeutic use ; Steroids/therapeutic use ; Patient Acuity ; Testosterone ; }, abstract = {OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies.

DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study).

MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD).

RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores.

CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.}, } @article {pmid38228250, year = {2024}, author = {Klinkhammer, S and Duits, AA and Deckers, K and Horn, J and Slooter, AJC and Verwijk, E and van Heugten, CM and Visser-Meily, JMA and , }, title = {A Biopsychosocial Approach to Persistent Post-COVID-19 Fatigue and Cognitive Complaints: Results of the Prospective Multicenter NeNeSCo Study.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {5}, pages = {826-834}, doi = {10.1016/j.apmr.2023.12.014}, pmid = {38228250}, issn = {1532-821X}, mesh = {Humans ; *COVID-19/complications/psychology ; Male ; Female ; Prospective Studies ; Middle Aged ; *Fatigue/etiology ; Netherlands ; Aged ; Adult ; SARS-CoV-2 ; Cognitive Dysfunction/etiology ; Magnetic Resonance Imaging ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: To evaluate whether psychological and social factors complement biomedical factors in understanding post-COVID-19 fatigue and cognitive complaints. Additionally, to incorporate objective (neuro-cognitive) and subjective (patient-reported) variables in identifying factors related to post-COVID-19 fatigue and cognitive complaints.

DESIGN: Prospective, multicenter cohort study.

SETTING: Six Dutch hospitals.

PARTICIPANTS: 205 initially hospitalized (March-June 2020), confirmed patients with SARS-CoV-2, aged ≥18 years, physically able to visit the hospital, without prior cognitive deficit, magnetic resonance imaging (MRI) contraindication, or severe neurologic damage post-hospital discharge (N=205).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Nine months post-hospital discharge, a 3T MRI scan and cognitive testing were performed and patients completed questionnaires. Medical data were retrieved from medical dossiers. Hierarchical regression analyses were performed on fatigue severity (Fatigue Severity Scale; FSS) and cognitive complaints (Cognitive Consequences after Intensive Care Admission; CLC-IC; dichotomized into CLC-high/low). Variable blocks: (1) Demographic and premorbid factors (sex, age, education, comorbidities), (2) Illness severity (ICU/general ward, PROMIS physical functioning [PROMIS-PF]), (3) Neuro-cognitive factors (self-reported neurological symptoms, MRI abnormalities, cognitive performance), (4) Psychological and social factors (Hospital Anxiety and Depression Scale [HADS], Utrecht Coping List, Social Support List), and (5) Fatigue or cognitive complaints.

RESULTS: The final models explained 60% (FSS) and 48% (CLC-IC) variance, with most blocks (except neuro-cognitive factors for FSS) significantly contributing. Psychological and social factors accounted for 5% (FSS) and 11% (CLC-IC) unique variance. Higher FSS scores were associated with younger age (P=.01), lower PROMIS-PF (P<.001), higher HADS-Depression (P=.03), and CLC-high (P=.04). Greater odds of CLC-high were observed in individuals perceiving more social support (OR=1.07, P<.05).

CONCLUSIONS: Results show that psychological and social factors add to biomedical factors in explaining persistent post-COVID-19 fatigue and cognitive complaints. Objective neuro-cognitive factors were not associated with symptoms. Findings highlight the importance of multidomain treatment, including psychosocial care, which may not target biologically-rooted symptoms directly but may reduce associated distress.}, } @article {pmid38226472, year = {2024}, author = {Di Ciaula, A and Liberale, L and Portincasa, P and Khalil, M and Galerati, I and Farella, I and Noto, A and JohnBritto, S and Moriero, M and Michelauz, C and Frè, F and Olivero, C and Bertolotto, M and Montecucco, F and Carbone, F and Bonfrate, L}, title = {Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients.}, journal = {European journal of clinical investigation}, volume = {54}, number = {4}, pages = {e14155}, doi = {10.1111/eci.14155}, pmid = {38226472}, issn = {1365-2362}, support = {DN. 1553 11.10.2022//#NEXTGENERATIONEU (NGEU), Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease/ ; RCR-2022-23682288//RCR-2022-23682288 - Rete CARDIOLOGICA- Integrated strategies for the study of tissue and molecular determinants of vulnerable atherosclerotic plaque - Procedura nota DGRIC n. 1401 del 13/04/2022 Fondo progetti reti EF 2022./ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Follow-Up Studies ; Neutrophils ; Prospective Studies ; SARS-CoV-2 ; Biomarkers ; }, abstract = {BACKGROUND: Long COVID symptoms are widely diffused and have a poorly understood pathophysiology, with possible involvement of inflammatory cytokines.

MATERIALS AND METHODS: A prospective follow-up study involved 385 unvaccinated patients, started 1 month after SARS-CoV-2 infection and continued for up to 12 months. We compared circulating biomarkers of neutrophil degranulation, endothelial and metabolic dysfunction in subjects with long COVID symptoms and in asymptomatic post-COVID controls.

RESULTS: The highest occurrence of symptoms (71%) was after 3 months from the infection, decreasing to 62.3% and 29.4% at 6 and 12 months, respectively. Compared to controls, long COVID patients had increased levels of the neutrophilic degranulation indices MMP-8 and MPO, of endothelial dysfunction indices L-selectin and P-selectin. Among indices of metabolic dysfunction, leptin levels were higher in long COVID patients than in controls.

CONCLUSION: In unvaccinated patients, symptoms may persist up to 1 year after acute COVID infection, with increased indices of neutrophil degranulation, endothelial and metabolic dysfunction. The clinical implications of specific inflammatory biomarkers require further attention, especially in individuals with fatigue and long COVID-linked cognitive dysfunctions.}, } @article {pmid38225989, year = {2024}, author = {Volckaerts, T and Quadflieg, K and Burtin, C and de Soomer, K and Oostveen, E and Roelant, E and Verhaegen, I and Ruttens, D and Lapperre, TS and Vissers, D}, title = {Evaluation of the learning effect on the 6-min walk distance in adults with long COVID.}, journal = {ERJ open research}, volume = {10}, number = {2}, pages = {}, pmid = {38225989}, issn = {2312-0541}, abstract = {There was no learning effect found on 6-min walk distance (6MWD) in patients with long COVID, performing a 6-min walk test twice. However, considerable variation in the difference between the two 6MWDs was observed: only 51% showed an increase. https://bit.ly/3H70G1r.}, } @article {pmid38225964, year = {2023}, author = {Tsapanou, A and Zoi, P and Kalligerou, F and Blekou, P and Sakka, P}, title = {Long COVID-19 Symptoms in People with Dementia or Mild Cognitive Impairment.}, journal = {Journal of Alzheimer's disease reports}, volume = {7}, number = {1}, pages = {1371-1375}, pmid = {38225964}, issn = {2542-4823}, abstract = {What is the impact of long COVID-19 on people with mild cognitive impairment (MCI) or dementia? Self-reported questionnaire was used for the report of long COVID-19 symptoms. People with MCI or dementia or their caregivers regarding patients' health were recruited COVID-19 throughout from the Athens Alzheimer's Association. We included 72 participants. Thirty had the diagnosis of MCI and 39 had dementia. Most symptoms lasted for 3-4 weeks. The majority of patients reported having all the symptoms, with fatigue being the major disturbance. The diagnosis and the management of long COVID-19 symptoms requires a more holistic and comprehensive approach.}, } @article {pmid38225804, year = {2024}, author = {Razzaghi, H and Forrest, CB and Hirabayashi, K and Wu, Q and Allen, AJ and Rao, S and Chen, Y and Bunnell, HT and Chrischilles, EA and Cowell, LG and Cummins, MR and Hanauer, DA and Higginbotham, M and Horne, BD and Horowitz, CR and Jhaveri, R and Kim, S and Mishkin, A and Muszynski, JA and Naggie, S and Pajor, NM and Paranjape, A and Schwenk, HT and Sills, MR and Tedla, YG and Williams, DA and Bailey, LC and , }, title = {Vaccine Effectiveness Against Long COVID in Children.}, journal = {Pediatrics}, volume = {153}, number = {4}, pages = {}, pmid = {38225804}, issn = {1098-4275}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; Retrospective Studies ; Prospective Studies ; Vaccine Efficacy ; }, abstract = {OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years.

METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination.

RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months.

CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.}, } @article {pmid38225587, year = {2024}, author = {Torrell, G and Puente, D and Jacques-Aviñó, C and Carrasco-Ribelles, LA and Violán, C and López-Jiménez, T and Royano, V and Cantón, AM and Medina-Perucha, L and Rodríguez-Giralt, I and Berenguera, A}, title = {Characterisation, symptom pattern and symptom clusters from a retrospective cohort of Long COVID patients in primary care in Catalonia.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {82}, pmid = {38225587}, issn = {1471-2334}, mesh = {Humans ; Female ; Male ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Spain/epidemiology ; Primary Health Care ; }, abstract = {BACKGROUND: Around 10% of people infected by SARS-COV-2 report symptoms that persist longer than 3 months. Little has been reported about sex differences in symptoms and clustering over time of non-hospitalised patients in primary care settings.

METHODS: This is a descriptive study of a cohort of mainly non-hospitalized patients with a persistence of symptoms longer than 3 months from the clinical onset in co-creation with the Long Covid Catalan affected group using an online survey. Recruitment was from March 2020 to June 2021. Exclusion criteria were being admitted to an ICU, < 18 years of age and not living in Catalonia. We focused on 117 symptoms gathered in 18 groups and performed cluster analysis over the first 21 days of infection, at 22-60 days, and ≥ 3 months.

RESULTS: We analysed responses of 905 participants (80.3% women). Median time between symptom onset and the questionnaire response date was 8.7 months. General symptoms (as fatigue) were the most prevalent with no differences by sex, age, or wave although its frequency decreased over time (from 91.8 to 78.3%). Dermatological (52.1% in women, 28.5% in men), olfactory (34.9% women, 20.9% men) and neurocognitive symptoms (70.1% women, 55.8% men) showed the greatest differences by sex. Cluster analysis showed five clusters with a predominance of Taste & smell (24.9%) and Multisystemic clusters (26.5%) at baseline and _Multisystemic (34.59%) and Heterogeneous (24.0%) at ≥3 months. The Multisystemic cluster was more prevalent in men. The Menstrual cluster was the most stable over time, while most transitions occurred from the Heterogeneous cluster to the Multisystemic cluster and from Taste & smell to Heterogeneous.

CONCLUSIONS: General symptoms were the most prevalent in both sexes at three-time cut-off points. Major sex differences were observed in dermatological, olfactory and neurocognitive symptoms. The increase of the Heterogeneous cluster might suggest an adaptation to symptoms or a non-specific evolution of the condition which can hinder its detection at medical appointments. A carefully symptom collection and patients' participation in research may generate useful knowledge about Long Covid presentation in primary care settings.}, } @article {pmid38222672, year = {2024}, author = {Packard, SE and Susser, E}, title = {Association of long COVID with housing insecurity in the United States, 2022-2023.}, journal = {SSM - population health}, volume = {25}, number = {}, pages = {101586}, pmid = {38222672}, issn = {2352-8273}, abstract = {OBJECTIVES: To assess the association of Long COVID with housing insecurity in the United States.

METHODS: To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms >3 months) and COVID-19 survivors who did not report long-term symptoms, we used survey-weighted regression models on 206,969 responses from the Household Pulse Survey, a representative cross-sectional survey of US households collected September 2022-April 2023. Among people with Long COVID, we additionally assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to-day life were associated with a higher prevalence of housing insecurity.

RESULTS: During the study period, 56,353 respondents with prior COVID-19 experienced symptoms lasting 3 months or longer (27%), representing an estimated 28 million US adults. After adjusting for demographic factors, people with Long COVID were 1.5-2 times as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.48, 95% CI 1.42-1.55), be behind on housing payments (PR 1.48, 95% CI 1.36-1.60), and face likely eviction or foreclosure (PR 1.86, 95% CI 1.58-2.18). The risk of housing insecurity was highest among low-income adults with Long COVID. Among people with Long COVID, functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity.

CONCLUSIONS: Compared with COVID-19 survivors who do not experience long-term symptoms, people with Long COVID are more likely to report indicators of housing insecurity, particularly those of lower socio-economic status, and those with functional limitations or long-term COVID-19 related symptoms impacting day-to-day life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.}, } @article {pmid38219763, year = {2024}, author = {Català, M and Mercadé-Besora, N and Kolde, R and Trinh, NTH and Roel, E and Burn, E and Rathod-Mistry, T and Kostka, K and Man, WY and Delmestri, A and Nordeng, HME and Uusküla, A and Duarte-Salles, T and Prieto-Alhambra, D and Jödicke, AM}, title = {The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.}, journal = {The Lancet. Respiratory medicine}, volume = {12}, number = {3}, pages = {225-236}, doi = {10.1016/S2213-2600(23)00414-9}, pmid = {38219763}, issn = {2213-2619}, mesh = {Adult ; Humans ; BNT162 Vaccine ; Cohort Studies ; *COVID-19/epidemiology/prevention & control ; *COVID-19 Vaccines/therapeutic use ; Estonia ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Spain ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2).

METHODS: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates.

FINDINGS: A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM).

INTERPRETATION: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults.

FUNDING: National Institute for Health and Care Research.}, } @article {pmid38218559, year = {2024}, author = {Patel, PR and Desai, JR and Plescia, M and Baggett, J and Briss, P}, title = {The Role of U.S. Public Health Agencies in Addressing Long COVID.}, journal = {American journal of preventive medicine}, volume = {66}, number = {5}, pages = {921-926}, doi = {10.1016/j.amepre.2024.01.004}, pmid = {38218559}, issn = {1873-2607}, mesh = {Humans ; United States/epidemiology ; *COVID-19/epidemiology/prevention & control ; *Public Health ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Public Health Administration ; }, } @article {pmid38218363, year = {2024}, author = {Skok, M}, title = {The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19.}, journal = {The international journal of biochemistry & cell biology}, volume = {168}, number = {}, pages = {106519}, doi = {10.1016/j.biocel.2024.106519}, pmid = {38218363}, issn = {1878-5875}, mesh = {Humans ; alpha7 Nicotinic Acetylcholine Receptor ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; *COVID-19/complications ; SARS-CoV-2 ; Antibodies ; *Receptors, Nicotinic ; }, abstract = {Post-Acute Sequelae of COVID-19 or Long COVID becomes evident some weeks to months following acute COVID-19. Symptoms include cognitive impairment and varying degrees of memory loss with no definitive etiologies or efficacious therapies forthcoming even after four years of the SARS-Cov2 pandemic virus. The aim of this review is to demonstrate the important role of α7 nicotinic acetylcholine receptors in both acute COVID-19 and Long COVID. Evidence presented implicates immune mechanisms stimulated by SARS-Cov-2 S-protein fragment 674-685 that possesses homology with α7-specific ligands. Cognitive dysfunctions observed in Long COVID patients may be derived from anti-idiotypic α7-specific antibodies stimulated by (674-685)-specific antibodies. Therapeutic interventions capable of neutralizing these antibodies and restoring full functions of α7 nicotinic acetylcholine receptors appear to be of paramount importance in post-acute sequelae of COVID-19.}, } @article {pmid38217931, year = {2024}, author = {Shamlan, G and Albreiki, M and Almasoudi, HO and Alshehri, LA and Ghaith, MM and Alharthi, AS and Aleanizy, FS}, title = {Nutritional status of elderly patients previously ill with COVID-19: Assessment with nutritional risk screening 2002 (NRS-2002) and mini nutritional assessment (MNA-sf).}, journal = {Journal of infection and public health}, volume = {17}, number = {2}, pages = {372-377}, doi = {10.1016/j.jiph.2023.11.005}, pmid = {38217931}, issn = {1876-035X}, mesh = {Humans ; Aged ; Nutritional Status ; Nutrition Assessment ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Risk Assessment ; *Malnutrition/complications/epidemiology/diagnosis ; }, abstract = {BACKGROUND: Long-term effects of COVID-19 showed a wide range of symptoms. Also, it was found that older patients were five times more likely than younger patients to develop long-COVID symptoms (1). This study aimed to investigate the use of Nutrition Risk Screening 2002 (NRS-2002) and the Mini Nutrition Assessment-Short Form (MNA-sf) among COVID-19 in elderly patients in Saudi Arabia.

METHODS: A total of (n = 159) COVID-19 elderly patients were recruited in the study; the relationship between patients' characteristics, including age, gender, Body Mass Index (BMI), infection history, vaccination and chronic disease were evaluated using NRS-2002 and MNA-sf. Multivariate logistic regression to estimate the Odd Ratio (OR) by comparing the OR of different variables between normal nutritional Status and at-risk and Cohen's kappa (κ) coefficient was assessed to analyse the agreement between both tools.

RESULTS: MNA-sf showed a positive association between age and malnutrition risk ≥ 66 years old P = 0.035. Both tools showed a negative association between BMI (P < 0.001 and P = 0.046), respectively and vaccination (P = 0.002 and P = 0.01), respectively, with risk for malnutrition. There was no significant association between Diabetes (DM) and malnutrition risk, but elderly Cardiovascular Disease (CVD) were at malnutrition risk using the NRS- 2002 tool P = 0.003. Inversely, people infected six months or more before malnutrition assessment have a lower risk of malnutrition P = 0.05.

CONCLUSIONS: Both tools were valuable and practical tools for screening elderly people with COVID-19 who are at nutritional risk and those in need of additional nutritional intervention. Further research needed to be applied in the relationship between nutritional status during and post-infectious disease for elderly people using cross-sectional and intervention studies in order to prevent malnutrition complications in Saudi Arabia.}, } @article {pmid38216825, year = {2024}, author = {Ketkar, A and Willey, V and Glasser, L and Dobie, C and Wenziger, C and Teng, CC and Dube, C and Hirpara, S and Cunningham, D and Verduzco-Gutierrez, M}, title = {Assessing the Burden and Cost of COVID-19 Across Variants in Commercially Insured Immunocompromised Populations in the United States: Updated Results and Trends from the Ongoing EPOCH-US Study.}, journal = {Advances in therapy}, volume = {41}, number = {3}, pages = {1075-1102}, pmid = {38216825}, issn = {1865-8652}, mesh = {Humans ; United States/epidemiology ; Retrospective Studies ; *COVID-19 Testing ; *COVID-19/epidemiology ; SARS-CoV-2 ; Health Care Costs ; Hospitalization ; }, abstract = {INTRODUCTION/METHODS: EPOCH-US is an ongoing, retrospective, observational cohort study among individuals identified in the Healthcare Integrated Research Database (HIRD[®]) with ≥ 12 months of continuous health plan enrollment. Data were collected for the HIRD population (containing immunocompetent and immunocompromised [IC] individuals), individual IC cohorts (non-mutually exclusive cohorts based on immunocompromising condition and/or immunosuppressive [IS] treatment), and the composite IC population (all unique IC individuals). This study updates previous results with addition of the general population cohort and data specifically for the year of 2022 (i.e., Omicron wave period). To provide healthcare decision-makers the most recent trends, this study reports incidence rates (IR) and severity of first SARS-CoV-2 infection; and relative risk, healthcare utilization, and costs related to first COVID-19 hospitalizations in the full year of 2022 and overall between April 2020 and December 2022.

RESULTS: These updated results showed a 2.9% prevalence of immune compromise in the population. From April 2020 through December 2022, the overall IR of COVID-19 was 115.7 per 1000 patient-years in the composite IC cohort and 77.8 per 1000 patient-years in the HIRD cohort. The composite IC cohort had a 15.4% hospitalization rate with an average cost of $42,719 for first COVID-19 hospitalization. Comparatively, the HIRD cohort had a 3.7% hospitalization rate with an average cost of $28,848 for first COVID-19 hospitalization. Compared to the general population, IC individuals had 4.3 to 23 times greater risk of hospitalization with first diagnosis of COVID-19. Between January and December 2022, hospitalizations associated with first COVID-19 diagnosis cost over $1 billion, with IC individuals (~ 3% of the population) generating $310 million (31%) of these costs.

CONCLUSION: While only 2.9% of the population, IC individuals had a higher risk of COVID-19 hospitalization and incurred higher healthcare costs across variants. They also disproportionately accounted for over 30% of total costs for first COVID-19 hospitalization in 2022, amounting to ~ $310 million. These data highlight the need for additional preventive measures to decrease the risk of developing severe COVID-19 outcomes in vulnerable IC populations.}, } @article {pmid38216180, year = {2024}, author = {Kosowan, L and Sanchez-Ramirez, DC and Katz, A}, title = {Understanding symptoms suggestive of long COVID syndrome and healthcare use among community-based populations in Manitoba, Canada: an observational cross-sectional survey.}, journal = {BMJ open}, volume = {14}, number = {1}, pages = {e075301}, pmid = {38216180}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Manitoba/epidemiology ; Quality of Life ; Canada ; Delivery of Health Care ; }, abstract = {OBJECTIVE: This study aims to characterise respondents who have COVID-19 and long COVID syndrome (LCS), and describe their symptoms and healthcare utilisation.

DESIGN: Observational cross-sectional survey.

SETTING: The one-time online survey was available from June 2022 to November 2022 to capture the experience of residents in Manitoba, Canada.

PARTICIPANT: Individuals shared their experience with COVID-19 including their COVID-19 symptoms, symptoms suggestive of LCS and healthcare utilisation. We used descriptive statistics to characterise patients with COVID-19, describe symptoms suggestive of LCS and explore respondent health system use based on presenting symptoms.

RESULTS: There were 654 Manitobans who responded to our survey, 616 (94.2%) of whom had or provided care to someone who had COVID-19, and 334 (54.2%) reported symptoms lasting 3 or more months. On average, respondents reported having 10 symptoms suggestive of LCS, with the most common being extreme fatigue (79.6%), issues with concentration, thinking and memory (76.6%), shortness of breath with activity (65.3%) and headaches (64.1%). Half of the respondents (49.2%) did not seek healthcare for COVID-19 or LCS. Primary care was sought by 66.2% respondents with symptoms suggestive of LCS, 15.2% visited an emergency department and 32.0% obtained care from a specialist or therapist. 62.6% of respondents with symptoms suggestive of LCS reported reducing work, school or other activities which demonstrate its impact on physical function and health-related quality of life.

CONCLUSION: Consistent with the literature, there are a variety of symptoms experienced among individuals with COVID-19 and LCS. Healthcare providers face challenge in providing care for patients with a wide range of symptoms unlikely to respond to a single intervention. These findings support the value of interdisciplinary COVID-19 clinics due to the complexity of the syndrome. This study confirms that data collected from the healthcare system do not provide a comprehensive reflection of LCS.}, } @article {pmid38214724, year = {2024}, author = {Ludwig, M and Schneider, K and Heß, S and Broich, K}, title = {[Establishment of the new "Health Data Lab" to provide data for science].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {67}, number = {2}, pages = {131-138}, pmid = {38214724}, issn = {1437-1588}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Germany ; *Delivery of Health Care ; Electronic Health Records ; }, abstract = {The analysis of real-world data (RWD) has become increasingly important in health research in recent years. With the BfArM Health Data Lab (HDL), which is currently being set up, researchers will in future be able to gain access to routine data from the statutory health insurance of around 74 million people in Germany. Data from electronic patient records can also be made available for research prospectively. In doing so, the Health Data Lab guarantees the highest data protection and IT security standards. The digital application process, the provision of data in secure processing environments as well as the features supporting the analyses such as catalogues of coding systems, a point-and-click analysis tool and predefined standard analyses increase user-friendliness for researchers. The use of the extensive health data accessible at HDL will open a wide range of future possibilities for improving the health system and the quality of care. This article begins by highlighting the advantages of the HDL and outlining the opportunities that the RWD offers for research in healthcare and for the population. The structure and central aspects of the HDL are explained afterwards. An outlook on the opportunities of linking different data is given. What the application and data usage processes at the HDL will look like is illustrated using the example of fictitious possibilities for analysing long COVID based on the routine data available at the HDL in the future.}, } @article {pmid38214079, year = {2024}, author = {Gebhard, CE and Sütsch, C and Gebert, P and Gysi, B and Bengs, S and Todorov, A and Deforth, M and Buehler, PK and Meisel, A and Schuepbach, RA and Zinkernagel, AS and Brugger, SD and Acevedo, C and Patriki, D and Wiggli, B and Beer, JH and Friedl, A and Twerenbold, R and Kuster, GM and Pargger, H and Tschudin-Sutter, S and Schefold, JC and Spinetti, T and Henze, C and Pasqualini, M and Sager, DF and Mayrhofer, L and Grieder, M and Tontsch, J and Franzeck, FC and Wendel Garcia, PD and Hofmaenner, DA and Scheier, T and Bartussek, J and Haider, A and Grämer, M and Mikail, N and Rossi, A and Zellweger, N and Opić, P and Portmann, A and von Känel, R and Pazhenkottil, AP and Messerli, M and Buechel, RR and Kaufmann, PA and Treyer, V and Siegemund, M and Held, U and Regitz-Zagrosek, V and Gebhard, C}, title = {Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {29}, number = {2}, pages = {}, pmid = {38214079}, issn = {1560-7917}, mesh = {Female ; Humans ; Male ; Adult ; Middle Aged ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Switzerland/epidemiology ; Prospective Studies ; SARS-CoV-2 ; Disease Progression ; }, abstract = {BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.}, } @article {pmid38212781, year = {2024}, author = {Azzam, A and Khaled, H and Refaey, N and Mohsen, S and El-Emam, OA and Dawood, N and Ahmed, HA and Soliman, OA and Mostafa, S and Ramadan, H and Mosa, M and Elmowafy, AOI and Rizk, SMA and Zaki, A and Hussien, M and Ahmed, A and Ezzat, AA and Hassan, FE}, title = {The burden of persistent symptoms after COVID-19 (long COVID): a meta-analysis of controlled studies in children and adults.}, journal = {Virology journal}, volume = {21}, number = {1}, pages = {16}, pmid = {38212781}, issn = {1743-422X}, mesh = {Adult ; Child ; Humans ; Ageusia/etiology ; Anosmia/etiology ; *COVID-19/complications/epidemiology ; *Post-Acute COVID-19 Syndrome/complications/epidemiology ; }, abstract = {BACKGROUND: Previous meta-analyses estimating the prevalence of the post-COVID-19 condition (PCC) were confounded by the lack of negative control groups. This may result in an overestimation of the prevalence of those experiencing PCC, as these symptoms are non-specific and common in the general population. In this study, we aimed to compare the burden of persistent symptoms among COVID-19 survivors relative to COVID-19-negative controls.

METHODS: A systematic literature search was conducted using the following databases (PubMed, Web of Science, and Scopus) until July 2023 for comparative studies that examined the prevalence of persistent symptoms in COVID-19 survivors. Given that many of the symptoms among COVID-19 survivors overlap with post-hospitalization syndrome and post-intensive care syndrome, we included studies that compare the prevalence of persistent symptoms in hospitalized COVID-19 patients relative to non-COVID-19 hospitalized patients and in non-hospitalized COVID-19 patients relative to healthy controls that reported outcomes after at least 3 months since infection. The results of the meta-analysis were reported as odds ratios with a 95% confidence interval based on the random effects model.

RESULTS: Twenty articles were included in this study. Our analysis of symptomatology in non-hospitalized COVID-19 patients compared to negative controls revealed that the majority of symptoms examined were not related to COVID-19 infection and appeared equally prevalent in both cohorts. However, non-COVID-19 hospitalized patients had higher odds of occurrence of certain symptoms like anosmia, ageusia, fatigue, dyspnea, and brain fog (P < 0.05). Particularly, anosmia and ageusia showed substantially elevated odds relative to the negative control group at 11.27 and 9.76, respectively, P < 0.05. In contrast, analysis of hospitalized COVID-19 patients compared to those hospitalized for other indications did not demonstrate significantly higher odds for the tested symptoms.

CONCLUSIONS: The persistent symptoms in COVID-19 survivors may result from hospitalization for causes unrelated to COVID-19 and are commonly reported among the general population. Although certain symptoms exhibited higher odds in non-hospitalized COVID-19 patients relative to controls, these symptoms are common post-viral illnesses. Therefore, the persistent symptoms after COVID-19 may not be unique to SARS-CoV-2. Future studies including well-matched control groups when investigating persistent symptoms in COVID-19 survivors are warranted to draw a firm conclusion.}, } @article {pmid38212633, year = {2024}, author = {Goldstein, DS}, title = {Post-COVID dysautonomias: what we know and (mainly) what we don't know.}, journal = {Nature reviews. Neurology}, volume = {20}, number = {2}, pages = {99-113}, pmid = {38212633}, issn = {1759-4766}, support = {/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; *Autonomic Nervous System Diseases ; Disease Progression ; }, abstract = {Following on from the COVID-19 pandemic is another worldwide public health challenge that is referred to variously as long COVID, post-COVID syndrome or post-acute sequelae of SARS-CoV-2 infection (PASC). PASC comes in many forms and affects all body organs. This heterogeneous presentation suggests involvement of the autonomic nervous system (ANS), which has numerous roles in the maintenance of homeostasis and coordination of responses to various stressors. Thus far, studies of ANS dysregulation in people with PASC have been largely observational and descriptive, based on symptom inventories or objective but indirect measures of cardiovascular function, and have paid little attention to the adrenomedullary, hormonal and enteric nervous components of the ANS. Such investigations do not consider the syndromic nature of autonomic dysfunction. This Review provides an update on the literature relating to ANS abnormalities in people with post-COVID syndrome and presents a theoretical perspective on how the ANS might participate in common features of PASC.}, } @article {pmid38212611, year = {2024}, author = {Graham, F}, title = {Daily briefing: Where long COVID is understudied and ignored.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-024-00040-9}, pmid = {38212611}, issn = {1476-4687}, } @article {pmid38212464, year = {2024}, author = {Yin, K and Peluso, MJ and Luo, X and Thomas, R and Shin, MG and Neidleman, J and Andrew, A and Young, KC and Ma, T and Hoh, R and Anglin, K and Huang, B and Argueta, U and Lopez, M and Valdivieso, D and Asare, K and Deveau, TM and Munter, SE and Ibrahim, R and Ständker, L and Lu, S and Goldberg, SA and Lee, SA and Lynch, KL and Kelly, JD and Martin, JN and Münch, J and Deeks, SG and Henrich, TJ and Roan, NR}, title = {Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.}, journal = {Nature immunology}, volume = {25}, number = {2}, pages = {218-225}, pmid = {38212464}, issn = {1529-2916}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AI174971/AI/NIAID NIH HHS/United States ; S10 RR028962/RR/NCRR NIH HHS/United States ; S10 OD018040/OD/NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; R01 AI159260/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Male ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; CD8-Positive T-Lymphocytes ; *COVID-19 ; Immunity, Humoral ; Antibodies, Viral ; Inflammation ; }, abstract = {Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4[+] T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8[+] T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.}, } @article {pmid38211737, year = {2024}, author = {Govednik, T and Lainšček, D and Kuhar, U and Lachish, M and Janežič, S and Štrbenc, M and Krapež, U and Jerala, R and Atlas, D and Manček-Keber, M}, title = {TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflammatory consequences.}, journal = {Antiviral research}, volume = {222}, number = {}, pages = {105806}, doi = {10.1016/j.antiviral.2024.105806}, pmid = {38211737}, issn = {1872-9096}, mesh = {Animals ; Humans ; Mice ; *COVID-19 ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; Peptides/pharmacology ; *Vaccines/pharmacology ; Thioredoxins/chemistry/metabolism/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Disulfides/pharmacology ; Giant Cells ; Protein Binding ; }, abstract = {After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19.}, } @article {pmid38206585, year = {2024}, author = {Sathyamoorthy, M and Sevak, RJ and Cabrera, J and Lopez, M and Fox, J and Shah, SA and Verduzco-Gutierrez, M}, title = {Enhanced External Counterpulsation Improves Cognitive Function of Persons With Long COVID.}, journal = {American journal of physical medicine & rehabilitation}, volume = {103}, number = {8}, pages = {734-739}, pmid = {38206585}, issn = {1537-7385}, mesh = {Humans ; Male ; *COVID-19/complications ; Female ; Retrospective Studies ; *Counterpulsation/methods ; *Cognitive Dysfunction/therapy/rehabilitation/etiology ; Aged ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cognition ; }, abstract = {OBJECTIVE: The aim of this study is to determine the effects of enhanced external counterpulsation (EECP) in patients with long COVID and objectively assessed cognitive impairment.

DESIGN: A retrospective evaluation of long COVID patients referred for EECP, with cognitive sequela, and having completed an objective digital assessment before and after therapy. Patients had either cognitive impairment or no cognitive impairment at baseline. We assessed changes in composite score using multifactor analysis of variance. Multiple linear and logistic regression analyses were conducted to evaluate several independent variables.

RESULTS: Eighty long COVID patients (38 cognitive impairment vs. 42 no cognitive impairment) were included for analyses. All baseline characteristics were well matched. There was significant improvement in composite score post EECP in those with objective cognitive impairment at baseline. There were no notable documented safety concerns.

CONCLUSIONS: This is the first study showing that EECP led to significant improvement in cognitive functioning of long COVID patients with objectively defined cognitive impairment. Although a lack of a negative control group is a limitation of this study, EECP seems to be highly safe and effective with the potential for widespread application.}, } @article {pmid38204779, year = {2023}, author = {Tseng, AA}, title = {Effectiveness of Meditation-based Interventions on Health Problems Caused by COVID-19 Pandemic: Narrative Review.}, journal = {International journal of yoga}, volume = {16}, number = {2}, pages = {72-78}, pmid = {38204779}, issn = {0973-6131}, abstract = {This article provides a quantitative review of the potential applications of meditation-based interventions (MBIs) in addressing the major health issues arising from the COVID-19 pandemic. The review assesses the effectiveness of MBIs on five prevalent disorders during the pandemic, namely depression, anxiety, stress, insomnia, and long COVID. This is achieved by selecting and scrutinizing seven studies that involve various types of online randomized controlled trials and utilize control group outcomes for effectiveness evaluation. The findings reveal a significant impact of MBIs on overall distress disorder, encompassing symptoms of depression, anxiety, and stress, with effectiveness ranging from 20.5% to 68.8%. The interventions also show moderate effectiveness on insomnia disorder with improvements between 5.2% and 38.5%. However, the effectiveness on long COVID disorder presents a mixed picture, with improvements varying from 0.0% to 71.2% across 13 related symptoms or qualities examined. This review offers compelling evidence supporting the effectiveness of MBIs in alleviating these five prevalent disorders resulting from the COVID-19 pandemic.}, } @article {pmid38203745, year = {2024}, author = {Mantle, D and Hargreaves, IP and Domingo, JC and Castro-Marrero, J}, title = {Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203745}, issn = {1422-0067}, mesh = {Humans ; *Fatigue Syndrome, Chronic/drug therapy/etiology ; Post-Acute COVID-19 Syndrome ; *Fibromyalgia/drug therapy/etiology ; Myalgia ; *Mitochondrial Diseases ; Dietary Supplements ; Ubiquinone/*analogs & derivatives ; }, abstract = {Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.}, } @article {pmid38203577, year = {2023}, author = {Constantinescu-Bercu, A and Lobiuc, A and Căliman-Sturdza, OA and Oiţă, RC and Iavorschi, M and Pavăl, NE and Șoldănescu, I and Dimian, M and Covasa, M}, title = {Long COVID: Molecular Mechanisms and Detection Techniques.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203577}, issn = {1422-0067}, support = {PN-III-Pl-1.1-PD-2021-0273, within PNCDI III//Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.}, } @article {pmid38203569, year = {2023}, author = {Imirowicz, I and Saifee, A and Henry, L and Tunkle, L and Popescu, A and Huang, P and Jakpor, J and Barbano, A and Goru, R and Gunawan, A and Sicilia, M and Ono, M and Bao, X and Lee, I}, title = {Unique tRNA Fragment Upregulation with SARS-CoV-2 but Not with SARS-CoV Infection.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203569}, issn = {1422-0067}, support = {R01 AI116812/NH/NIH HHS/United States ; R21 AI166543/AI/NIAID NIH HHS/United States ; R01 AI116812/AI/NIAID NIH HHS/United States ; R21 AG069226/AG/NIA NIH HHS/United States ; R21 AG069226/NH/NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/genetics ; Up-Regulation ; Down-Regulation ; RNA, Transfer/genetics ; Thyrotropin-Releasing Hormone ; }, abstract = {Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.}, } @article {pmid38202234, year = {2023}, author = {Scott, C and Hall, S and Zhou, J and Lehmann, C}, title = {Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202234}, issn = {2077-0383}, abstract = {Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute "long" COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.}, } @article {pmid38202052, year = {2023}, author = {Pietruszka-Wałęka, E and Rząd, M and Żabicka, M and Rożyńska, R and Miklusz, P and Zieniuk-Lesiak, E and Jahnz-Różyk, K}, title = {Impact of Symptomatology, Clinical and Radiological Severity of COVID-19 on Pulmonary Function Test Results and Functional Capacity during Follow-Up among Survivors.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202052}, issn = {2077-0383}, abstract = {One of the most commonly observed complications after COVID-19 is persistent pulmonary impairment. The aim of this study was to evaluate the impact of individual factors during the acute phase of COVID-19 on subsequent pulmonary function test results. The study involved 46 patients who were admitted to hospital due to respiratory failure caused by SARS-CoV-2 and who were assessed during follow-up visits at 3 and 9 months after discharge. Patients were divided into two subgroups according to the severity of respiratory failure. The severe group included patients requiring mechanical ventilation or HFNOT. The results of the study showed that a severe course of the disease was associated with a lower FVC and a higher FEV1/FVC ratio 3 months after discharge (both p < 0.05). In addition, it has been revealed that the length of hospitalization is a factor that negatively impacts the FEV1, FVC and TLC values measured at follow-up after 3 months. Furthermore, the obtained results identify the presence of cough in the acute phase of the disease as a factor having a positive impact on several PFT parameters (especially the FEV1/FVC ratio) as well as the 6MWT outcome after 3 months. The FVC improved significantly (p < 0.05) between the follow-up visits. The findings may indicate that COVID-19-induced respiratory dysfunction is usually temporary and spontaneously resolves during recovery. Recovery is slower in those who required more intensive oxygenation. The results of this study may be useful in identifying patients who require more intensive and longer rehabilitation after COVID-19.}, } @article {pmid38200486, year = {2024}, author = {Kvale, G and Søfteland, E and Jürgensen, M and Wilhelmsen-Langeland, A and Haugstvedt, A and Hystad, SW and Ødegaard-Olsen, ØT and Aarli, BB and Rykken, S and Frisk, B}, title = {First trans-diagnostic experiences with a novel micro-choice based concentrated group rehabilitation for patients with low back pain, long COVID, and type 2 diabetes: a pilot study.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {12}, pmid = {38200486}, issn = {1741-7015}, support = {389457//EkstraStiftelsen Helse og Rehabilitering (Stiftelsen Dam)/ ; 389461//EkstraStiftelsen Helse og Rehabilitering (Stiftelsen Dam)/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *COVID-19 ; COVID-19 Testing ; *Diabetes Mellitus, Type 2/diagnosis ; *Low Back Pain/diagnosis ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The health care is likely to break down unless we are able to increase the level of functioning for the growing number of patients with complex, chronic illnesses. Hence, novel high-capacity and cost-effective treatments with trans-diagnostic effects are warranted. In accordance with the protocol paper, we aimed to examine the acceptability, satisfaction, and effectiveness of an interdisciplinary micro-choice based concentrated group rehabilitation for patients with chronic low back pain, long COVID, and type 2 diabetes.

METHODS: Patients with low back pain > 4 months sick-leave, long COVID, or type 2 diabetes were included in this clinical trial with pre-post design and 3-month follow-up. The treatment consisted of three phases: (1) preparing for change, (2) the concentrated intervention for 3-4 days, and (3) integrating change into everyday life. Patients were taught and practiced how to monitor and target seemingly insignificant everyday micro-choices, in order to break the patterns where symptoms or habits contributed to decreased levels of functioning or increased health problems. The treatment was delivered to groups (max 10 people) with similar illnesses. Client Satisfaction Questionnaire (CSQ-8)) (1 week), Work and Social Adjustment Scale (WSAS), Brief Illness Perception Questionnaire (BIPQ), and self-rated health status (EQ-5D-5L) were registered at baseline and 3-month follow-up.

RESULTS: Of the 241 included participants (57% women, mean age 48 years, range 19-84), 99% completed the concentrated treatment. Treatment satisfaction was high with a 28.9 (3.2) mean CSQ-8-score. WSAS improved significantly from baseline to follow-up across diagnoses 20.59 (0.56) to 15.76 (0.56). BIPQ improved from: 22.30 (0.43) to 14.88 (0.47) and EQ-5D-5L: 0.715 (0.01) to 0.779 (0.01)), all P<0.001.

CONCLUSIONS: Across disorders, the novel approach was associated with high acceptability and clinically important improvements in functional levels, illness perception, and health status. As the concentrated micro-choice based treatment format might have the potential to change the way we deliver rehabilitation across diagnoses, we suggest to proceed with a controlled trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05234281.}, } @article {pmid38199938, year = {2024}, author = {Roder, S and Mohacsi, LM and Schmachtenberg, T}, title = {[Experiences of people with Long COVID in their medical accompaniment and in the social environment].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {185}, number = {}, pages = {27-34}, doi = {10.1016/j.zefq.2023.11.009}, pmid = {38199938}, issn = {2212-0289}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Germany ; Social Environment ; Family ; }, abstract = {BACKGROUND: Permanent health impairments after a COVID-19 infection can lead to a lack of social participation and pronounced emotional stress. The aim of this study was to find out how Long COVID affects the social activities of those affected and understand the role that medical support and the immediate social environment play in this.

METHODS: Between January and May 2022, 25 participants with long COVID were interviewed about their health situation, their perception of health care in Germany, and their social and professional context. The interviews, which were mainly conducted online, were analyzed for content, and the results were assessed using lifeworld-theoretical approaches.

RESULTS: The participants reported a variety of health symptoms such as fatigue, shortness of breath, and cognitive impairments. The majority of respondents had a pessimistic attitude toward a timely recovery. Most participants perceived the medical support for long COVID as inadequate. Long waiting times for specialist appointments and the lack of acceptance of the health impairment by some doctors lead to an increase in existing uncertainties. Long COVID also had a major impact on respondents' social life. Many participants referred to a burdensome decline in the number of meetings with family and friends. Many respondents avoided physical contact with friends and family members due to a high level of fear of infection. Some participants explained that they separated themselves from people in their environment because they did not take their precarious situation seriously. However, an important resource was the close circle of family and friends from whom the majority of the interviewees received support.

DISCUSSION: While other research studies particularly emphasize the comprehensive psychological and emotional consequences of long COVID, such as identity conflicts, existential angst, or depression, the present study shows that a lack of understanding from medical professionals as well as heavily delayed treatment leave the interviewees in a state of emotional void.

CONCLUSIONS: The findings show a considerable need for support among people with health impairments after a COVID-19 infection. Empathic and empirically based counseling and support by general practitioners as well as improvement of access to rehabilitative services can provide substantial support for people with long COVID.}, } @article {pmid38198795, year = {2024}, author = {Lunt, J and Hemming, S and Elander, J and Burton, K and Hanney, B}, title = {Sustaining work ability amongst female professional workers with long COVID.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {104-112}, doi = {10.1093/occmed/kqad134}, pmid = {38198795}, issn = {1471-8405}, mesh = {Adult ; Male ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; Qualitative Research ; Work Capacity Evaluation ; *COVID-19 ; Return to Work/psychology ; }, abstract = {BACKGROUND: Long COVID (LC) compromises work ability (WA). Female worker WA has been more adversely impacted than WA in men. Exploration of lived experiences could elucidate the WA support required.

AIMS: To explore the working conditions and circumstances experienced as affecting sustained WA amongst female workers with LC, to help mitigate worklessness risks.

METHODS: Online semi-structured qualitative interviews were conducted with 10 female workers self-reporting or formally diagnosed with LC who had made some attempt to return to work (RTW). Interviews were analysed using template analysis to map themes informing WA enablers and obstacles onto a biopsychosocial model of rehabilitation.

RESULTS: All participants were professionals working in an employed or self-employed capacity. Key themes reflecting circumstances that afforded sustained WA included the autonomy over where, when and how to work indicated as facilitated by a professional role, rapid health care access, predominantly sedentary work, competent colleagues able to cover for transient reduced WA, a strong interface between specialist health and management support, and accessible organizational policies that steer health management according to equity rather than equality. Highly flexible, iterative, co-produced RTW planning, tolerant of fluctuating symptom expression appears vital. In return for providing such flexibility, participants felt that employers' workforce diversity and competence would be protected and that workers would need to reciprocate flexibility.

CONCLUSIONS: These qualitatively derived findings of workers' lived experiences add to existing guidance on supporting WA for people struggling with LC. Moreover, the same principles seem appropriate for tackling worklessness amongst working-age adults with complex long-term health conditions.}, } @article {pmid38198481, year = {2024}, author = {Troxel, AB and Bind, MC and Flotte, TJ and Cordon-Cardo, C and Decker, LA and Finn, AV and Padera, RF and Reichard, RR and Stone, JR and Adolphi, NL and Casimero, FVC and Crary, JF and Elifritz, J and Faustin, A and Ghosh, SKB and Krausert, A and Martinez-Lage, M and Melamed, J and Mitchell, RA and Sampson, BA and Seifert, AC and Simsir, A and Adams, C and Haasnoot, S and Hafner, S and Siciliano, MA and Vallejos, BB and Del Boccio, P and Lamendola-Essel, MF and Young, CE and Kewlani, D and Akinbo, PA and Parent, B and Chung, A and Cato, TC and Mudumbi, PC and Esquenazi-Karonika, S and Wood, MJ and Chan, J and Monteiro, J and Shinnick, DJ and Thaweethai, T and Nguyen, AN and Fitzgerald, ML and Perlowski, AA and Stiles, LE and Paskett, ML and Katz, SD and Foulkes, AS and , }, title = {Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0285645}, pmid = {38198481}, issn = {1932-6203}, support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19 ; SARS-CoV-2 ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Disease Progression ; Risk Factors ; }, abstract = {IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.

METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes.

DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.}, } @article {pmid38197253, year = {2024}, author = {Hitchcock, S and Cintron, SA and Kasuske, L and J Diaz, F and Pierce, J}, title = {Post-COVID-19 Condition in Military Personnel.}, journal = {Military medicine}, volume = {189}, number = {5-6}, pages = {e1277-e1281}, doi = {10.1093/milmed/usad453}, pmid = {38197253}, issn = {1930-613X}, support = {11189-N23-B01//Tri-Service Nursing Research Program/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Military Personnel/statistics & numerical data ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Pandemics ; }, abstract = {INTRODUCTION: During the COVID-19 pandemic, a significant number of individuals experienced persistent symptoms, collectively termed post-COVID-19 condition (PCC) by the World Health Organization. While civilian prevalence has been extensively studied, little is known about PCC in military personnel. This article highlights the need for increased awareness, documentation, and research on PCC within the military context, utilizing the Defense Health Agency database.

MATERIALS AND METHODS: A keyword search of the PubMed, CINAHL, and Web of Science databases was performed utilizing the keywords: military, post-COVID conditions, long COVID-19, and post-COVID19 syndrome. A five-stage integrative review framework was used to analyze 40 reports and research articles published from 2019 to 2023 to assess the current state of PCC research, including epidemiology, severe acute respiratory syndrome coronavirus 2 variants, pathophysiology, and prevalence in military personnel.

RESULTS: Our review revealed a notable gap in research on PCC within the military population, with only a few mentions in the literature. A key finding was the association between immunization status, symptom severity, and ethnicity in PCC development.

CONCLUSION: To comprehensively address PCC in military personnel, it is imperative to foster both awareness and documentation. Creating a centralized Defense Health Agency-DoD repository for active duty service members with PCC diagnoses offers a valuable opportunity to conduct trend analysis, identify missed cases, and better understand the individual and military readiness implications of this condition. Additionally, to address the educational needs of clinicians, it is essential to develop continuing medical education and continuing nursing education programs focusing on PCC signs, symptoms, and their impact on readiness. Furthermore, randomized controlled trials and longitudinal experimental clinical trials are essential for monitoring service members over time, providing valuable insights into the course of PCC and potential interventions. These research endeavors collectively contribute to improving the health, readiness, and care of military personnel affected by PCC.}, } @article {pmid38196610, year = {2023}, author = {Wei, WQ and Guardo, C and Gandireddy, S and Yan, C and Ong, H and Kerchberger, V and Dickson, A and Pfaff, E and Master, H and Basford, M and Tran, N and Mancuso, S and Syed, T and Zhao, Z and Feng, Q and Haendel, M and Lunt, C and Ginsburg, G and Chute, C and Denny, J and Roden, D}, title = {Genetic and Survey Data Improves Performance of Machine Learning Model for Long COVID.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38196610}, issn = {2693-5015}, support = {R01 AG069900/AG/NIA NIH HHS/United States ; R01 GM139891/GM/NIGMS NIH HHS/United States ; U01 HG011181/HG/NHGRI NIH HHS/United States ; }, abstract = {Over 200 million SARS-CoV-2 patients have or will develop persistent symptoms (long COVID). Given this pressing research priority, the National COVID Cohort Collaborative (N3C) developed a machine learning model using only electronic health record data to identify potential patients with long COVID. We hypothesized that additional data from health surveys, mobile devices, and genotypes could improve prediction ability. In a cohort of SARS-CoV-2 infected individuals (n=17,755) in the All of Us program, we applied and expanded upon the N3C long COVID prediction model, testing machine learning infrastructures, assessing model performance, and identifying factors that contributed most to the prediction models. For the survey/mobile device information and genetic data, extreme gradient boosting and a convolutional neural network delivered the best performance for predicting long COVID, respectively. Combined survey, genetic, and mobile data increased specificity and the Area Under Curve the Receiver Operating Characteristic score versus the original N3C model.}, } @article {pmid38195523, year = {2024}, author = {Bartak, M and Bąska, P and Chodkowski, M and Tymińska, B and Bańbura, MW and Cymerys, J}, title = {Neurons cytoskeletal architecture remodeling during the replication cycle of mouse coronavirus MHV-JHM: a morphological in vitro study.}, journal = {BMC veterinary research}, volume = {20}, number = {1}, pages = {18}, pmid = {38195523}, issn = {1746-6148}, support = {2021/41/N/NZ6/04383//Narodowym Centrum Nauki/ ; 2021/41/N/NZ6/04383//Narodowym Centrum Nauki/ ; }, mesh = {Animals ; Mice ; *Murine hepatitis virus ; Post-Acute COVID-19 Syndrome/veterinary ; *COVID-19/veterinary ; Antigens, Viral ; Neurons ; SARS-CoV-2 ; *Rodent Diseases ; }, abstract = {Nowadays, the population is still struggling with a post-COVID19 syndrome known as long COVID, including a broad spectrum of neurological problems. There is an urgent need for a better understanding and exploration of the mechanisms of coronavirus neurotropism. For this purpose, the neurotropic strain of mouse hepatitis virus (MHV-JHM) originating from the beta-coronavirus genus, the same as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been used. The role of the cytoskeleton during virus replication in neurons in vitro was determined to understand the mechanisms of MHV-JHM neuroinfection. We have described for the first time the changes of actin filaments during MHV-JHM infection. We also observed productive replication of MHV-JHM in neurons during 168 h p.i. and syncytial cytopathic effect. We discovered that the MHV-JHM strain modulated neuronal cytoskeleton during infection, which were manifested by: (i) condensation of actin filaments in the cortical layer of the cytoplasm, (ii) formation of microtubule cisternae structures containing viral antigen targeting viral replication site (iii) formation of tunneling nanotubes used by MHV-JHM for intercellular transport. Additionally, we demonstrated that the use of cytoskeletal inhibitors have reduced virus replication in neurons, especially noscapine and nocodazole, the microtubule shortening factors.}, } @article {pmid38195495, year = {2024}, author = {Ma, Y and Zhang, L and Wei, R and Dai, W and Zeng, R and Luo, D and Jiang, R and Zhuo, Z and Yang, Q and Li, J and Leung, FW and Duan, C and Sha, W and Chen, H}, title = {Risks of digestive diseases in long COVID: evidence from a population-based cohort study.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {14}, pmid = {38195495}, issn = {1741-7015}, support = {82171698//National Natural Science Foundation of China/ ; 82170561//National Natural Science Foundation of China/ ; 81300279//National Natural Science Foundation of China/ ; 81741067//National Natural Science Foundation of China/ ; 82273727//National Natural Science Foundation of China/ ; G2022030047L//Project to Attract Foreign Experts from Minister of Science and Technology of China/ ; 2022A1515012081//Natural Science Foundation of Guangdong Province/ ; KD0120220129//Foreign Distinguished Teacher Program of Guangdong Science and Technology Department/ ; DFJH201803//Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ ; KJ012019099//Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ ; KJ012021143//Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ ; KY012021183//Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital/ ; U23A20408//National Natural Science Foundation of China Regional Innovation and Development Joint Foundation/ ; 2021B1515020003//Natural Science Foundation for Distinguished Young Scholars of Guangdong Province/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cohort Studies ; Reinfection ; Retrospective Studies ; SARS-CoV-2 ; *Digestive System Diseases/epidemiology ; *Gastroesophageal Reflux ; *Liver Diseases ; }, abstract = {BACKGROUND: In the post-pandemic era, a wide range of COVID-19 sequelae is of growing health concern. However, the risks of digestive diseases in long COVID have not been comprehensively understood. To investigate the long-term risk of digestive diseases among COVID patients.

METHODS: In this large-scale retrospective cohort study with up to 2.6 years follow-up (median follow-up: 0.7 years), the COVID-19 group (n = 112,311), the contemporary comparison group (n = 359,671) and the historical comparison group (n = 370,979) predated the COVID-19 outbreak were built using UK Biobank database. Each digestive outcome was defined as the diagnosis 30 days or more after the onset of COVID-19 infection or the index date. Hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting.

RESULTS: Compared with the contemporary comparison group, patients with previous COVID-19 infection had higher risks of digestive diseases, including gastrointestinal (GI) dysfunction (HR 1.38 (95% CI 1.26 to 1.51)); peptic ulcer disease (HR 1.23 (1.00 to 1.52)); gastroesophageal reflux disease (GERD) (HR 1.41 (1.30 to 1.53)); gallbladder disease (HR 1.21 (1.06 to 1.38)); severe liver disease (HR 1.35 (1.03 to 1.76)); non-alcoholic liver disease (HR 1.27 (1.09 to 1.47)); and pancreatic disease (HR 1.36 (1.11 to 1.66)). The risks of GERD were increased stepwise with the severity of the acute phase of COVID-19 infection. Even after 1-year follow-up, GERD (HR 1.64 (1.30 to 2.07)) and GI dysfunction (HR 1.35 (1.04 to 1.75)) continued to pose risks to COVID-19 patients. Compared to those with one SARS-CoV-2 infection, reinfected patients were at a higher risk of pancreatic diseases (HR 2.57 (1.23 to 5.38)). The results were consistent when the historical cohort was used as the comparison group.

CONCLUSIONS: Our study provides insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing digestive diseases. The risks exhibited a stepwise escalation with the severity of COVID-19, were noted in cases of reinfection, and persisted even after 1-year follow-up. This highlights the need to understand the varying risks of digestive outcomes in COVID-19 patients over time, particularly those who experienced reinfection, and develop appropriate follow-up strategies.}, } @article {pmid38195459, year = {2024}, author = {Wang, C and Tan, W and Liu, X and He, M and Zeng, S and Sun, M and Yan, L and Li, M and Zhan, K and Wang, K and Li, Q}, title = {Habitual salt preference worsens blood pressure in hospitalized hypertensive patients with omicron infection under epidemic-related stress.}, journal = {BMC public health}, volume = {24}, number = {1}, pages = {134}, pmid = {38195459}, issn = {1471-2458}, support = {12171396//National Natural Science Foundation of China/ ; 32171152//National Natural Science Foundation of China/ ; }, mesh = {*Post-Acute COVID-19 Syndrome ; Blood Pressure ; Stress, Psychological ; *Hypertension/epidemiology ; *Sodium Chloride, Dietary/adverse effects ; Humans ; Patients ; SARS-CoV-2 ; }, abstract = {BACKGROUND: We investigated the synergistic effect of stress and habitual salt preference (SP) on blood pressure (BP) in the hospitalized Omicron-infected patients.

METHODS: From 15,185 hospitalized Omicron-infected patients who reported having high BP or hypertension, we recruited 662 patients. All patients completed an electronic questionnaire on diet and stress, and were required to complete morning BP monitoring at least three times.

RESULTS: The hypertensive group (n = 309) had higher habitual SP (P = 0.015) and COVID-19 related stress (P < 0.001), and had longer hospital stays (7.4 ± 1.5 days vs. 7.2 ± 0.5 days, P = 0.019) compared with controls (n = 353). After adjusting for a wide range of covariates including Omicron epidemic-related stress, habitual SP was found to increase both systolic (4.9 [95% confidence interval (CI), 2.3-7.4] mmHg, P < 0.001) and diastolic (2.1 [95%CI, 0.6-3.6] mmHg, P = 0.006) BP in hypertensive patients, and increase diastolic BP (2.0 [95%CI, 0.2-3.7] mmHg, P = 0.026) in the control group. 31 (8.8%) patients without a history of hypertension were discovered to have elevated BP during hospitalization, and stress was shown to be different in those patients (P < 0.001). In contrast, habitual SP was more common in hypertensive patients with uncontrolled BP, compared with patients with controlled BP (P = 0.002).

CONCLUSIONS: Habitual SP and psychosocial stress were associated with higher BP in Omicron-infected patients both with and without hypertension. Nonpharmaceutical intervention including dietary guidance and psychiatric therapy are crucial for BP control during the long COVID-19 period.}, } @article {pmid38195129, year = {2024}, author = {}, title = {Do allergic conditions increase the risk of developing Long-COVID after SARS-CoV-2 infection?.}, journal = {Neurosciences (Riyadh, Saudi Arabia)}, volume = {29}, number = {1}, pages = {68}, pmid = {38195129}, issn = {1319-6138}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Hypersensitivity ; }, } @article {pmid38194938, year = {2024}, author = {Mennella, S and Alicino, C and Anselmo, M and Carrega, G and Ficarra, G and Garra, L and Gastaldo, A and Gnerre, P and Lillo, F and Tassara, R and Terrile, A and Milanese, M and , }, title = {COVID-19 after 2 Years from Hospital Discharge: A Pulmonary Function and Chest Computed Tomography Follow-Up Study.}, journal = {Respiration; international review of thoracic diseases}, volume = {103}, number = {1}, pages = {22-31}, doi = {10.1159/000535732}, pmid = {38194938}, issn = {1423-0356}, mesh = {Humans ; *COVID-19/diagnostic imaging ; Follow-Up Studies ; Patient Discharge ; Lung/diagnostic imaging ; Tomography, X-Ray Computed/methods ; Hospitals ; }, abstract = {INTRODUCTION: Serial follow-up with pulmonary function testing (PFT) and chest computed tomography (CT) after severe COVID-19 are recommended. As a result, many longitudinal studies have been published on COVID-19 of different grade of severity up to 1-year follow-up. Therefore, we aimed at a long-term observational study throughout 2 years after severe COVID-19.

METHODS: Severe COVID-19 patients were consecutively recruited after hospital discharge between March and June 2020 and prospectively followed up for 24 months, with mMRC dyspnea scale and PFT at 6, 12, and 24 months. Chest CT was performed when clinically indicated.

RESULTS: One hundred one patients enrolled completed the observational study. At 24 months, those with reduced total lung capacity (TLC) were 16%, associated with fibrotic ground glass opacity (GGO) and mMRC score >1, respectively, in 75% and 69% of them. At 24 months, those with a reduced diffusing capacity of the lung for CO were 41%, associated with fibrotic GGO and mMRC score >1, respectively, in 53% and 22% of them.

CONCLUSION: Two years after hospitalization for severe COVID-19, a non-negligible number of patients still suffer from "long COVID" due to respiratory damage.}, } @article {pmid38193771, year = {2024}, author = {Bobak, L and Dorney, I and Kovacevich, A and Barnett, B and Kaelber, DC}, title = {Preexisting Psychiatric Conditions as Risk Factors for Diagnosed Long COVID-19 Syndrome Within Aggregated Electronic Health Record Data.}, journal = {Psychosomatic medicine}, volume = {86}, number = {3}, pages = {132-136}, pmid = {38193771}, issn = {1534-7796}, support = {UL1 TR002548/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Electronic Health Records ; *COVID-19/diagnosis/epidemiology/complications ; *Depressive Disorder, Major/complications ; *Mental Disorders/epidemiology/etiology ; Risk Factors ; Retrospective Studies ; }, abstract = {OBJECTIVE: This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions.

METHODS: The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome.

RESULTS: Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code "U09: post-COVID-19 condition." After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47-1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57-1.71), mood disorders (RR = 1.65; 95% CI = 1.57-1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21-1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56-1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06-1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22-1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis.

CONCLUSIONS: Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection.}, } @article {pmid38192617, year = {2024}, author = {Eitze, S and Sprengholz, P and Korn, L and Shamsrizi, P and Felgendreff, L and Betsch, C}, title = {Vicarious experiences of long COVID: A protection motivation theory analysis for vaccination intentions.}, journal = {Vaccine: X}, volume = {16}, number = {}, pages = {100417}, pmid = {38192617}, issn = {2590-1362}, abstract = {CONTEXT: Long COVID can appear as a severe late consequence (sequela) of a COVID-19 infection, leading to the inability to work or participate in social life for an unknown amount of time. To see friends or family struggling with long COVID might influence people's risk perceptions, vaccine efficacy expectations, and self-efficacy perceptions to prevent COVID-19 and its consequences.

METHODS: In an online survey in August 2022, n = 989 German-speaking participants indicated whether they knew someone who suffered from long COVID illness. Four dimensions of protection motivation theory (PMT) were assessed afterwards, as well as vaccination intentions.

RESULTS: Multiple mediation analysis with participants who knew vs. didn't know someone with long COVID (n = 767) showed that knowing someone with long COVID was associated with higher perceived affective and cognitive risk of long COVID-19 as well as higher perceived vaccine efficacy. Self-efficacy, i.e., the ease to protect oneself against long COVID, was lower in participants who knew long-COVID patients. Indirect positive effects for response efficacy and affective risk suggest that vicarious experience with long COVID is associated with increased intentions to get a COVID-19 vaccine.

CONCLUSION: The protection from long COVID through vaccination are relevant aspects for individual decisions and health communication.}, } @article {pmid38191766, year = {2024}, author = {Deodato, M and Qualizza, C and Martini, M and Mazzari, L and Furlanis, G and Buoite Stella, A and Manganotti, P}, title = {Efficacy of dual-task augmented reality rehabilitation in non-hospitalized adults with self-reported long COVID fatigue and cognitive impairment: a pilot study.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {45}, number = {4}, pages = {1325-1333}, pmid = {38191766}, issn = {1590-3478}, mesh = {Adult ; Female ; Humans ; Cognition/physiology ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; Self Report ; Hand Strength ; *Augmented Reality ; *COVID-19/complications ; *Cognitive Dysfunction/etiology ; }, abstract = {BACKGROUND: Cognitive impairment and chronic fatigue represent common characteristics of the long COVID syndrome. Different non-pharmacological treatments have been proposed, and physiotherapy has been proposed to improve the symptoms. This study aimed to evaluate the effects of a dual-task augmented reality rehabilitation protocol in people with long COVID fatigue and cognitive impairment.

METHODS AND MATERIALS: Ten non-hospitalized adults with reported fatigue and "brain fog" symptoms after COVID (7/10 females, 50 years, range 41-58) who participated in 20 sessions of a 1-h "dual-task" training, were compared to 10 long COVID individuals with similar demographics and symptoms (9/10 females, 56 years, range 43-65), who did not participate to any rehabilitation protocol. Cognitive performance was assessed with the Trail Making Test (TMT-A and -B) and Frontal Assessment Battery (FAB), and cardiovascular and muscular fatigue were assessed with the fatigue severity scale (FSS), six-minute walking test and handgrip endurance. Finally, transcranial magnetic stimulation (TMS) investigated cortical excitability.

RESULTS: The mixed-factors analysis of variance found a significant interaction effect only in cognitive performance evaluation, suggesting TMT-B execution time decreased (- 15.9 s, 95% CI 7.6-24.1, P = 0.001) and FAB score improved (1.88, 95% CI 2.93-0.82, P = 0.002) only in the physiotherapy group. For the remaining outcomes, no interaction effect was found, and most parameters similarly improved in the two groups.

CONCLUSION: The preliminary results from this study suggest that dual-task rehabilitation could be a feasible protocol to support cognitive symptoms recovery after COVID-19 and could be helpful in those individuals suffering from persisting and invalidating symptoms.}, } @article {pmid38191556, year = {2024}, author = {Kim, Y and Bae, S and Chang, HH and Kim, SW}, title = {Characteristics of long COVID and the impact of COVID-19 vaccination on long COVID 2 years following COVID-19 infection: prospective cohort study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {854}, pmid = {38191556}, issn = {2045-2322}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Prospective Studies ; Quality of Life ; Vaccination ; }, abstract = {This prospective cohort study aimed to identify characteristics of long COVID and any potential mitigating effects of COVID-19 vaccinations in patients 24 months following COVID-19 infection. Adult patients diagnosed with COVID-19 between February 17, 2020, and March 24, 2020, were scheduled to visit the study hospital four times (6, 12, 18, and 24 months after infection) to assess their symptoms, quality of life, and mental health. Among the 235 patients, 121 (51.5%) completed the study visits. Of these, 59.5% were female, with a median age of 52 years. Mild to moderate disease severity were identified in 101 (83.4%) patients. A total of 75 participants (62.0%) were still experiencing long COVID symptoms 24 months after acute infection. Fatigue, amnesia, difficulty concentrating, and insomnia were the most common symptoms. The frequency of neuropsychiatric symptoms did not differ based on vaccination status or the number of doses received. Quality of life improved over time for the participants, but 32.2% of respondents still reported anxiety/depression at the end of the study. Overall, our cohort demonstrates that long COVID can persist up to 24 months after COVID-19 infection, affecting mental health and quality of life.}, } @article {pmid38190991, year = {2024}, author = {Rutsch, M and Schüller, PO and Buhr-Schinner, H and Gross, T and Deck, R}, title = {[Pneumological Rehabilitation in Long COVID - A Comparative Exploratory Longitudinal Study of Long COVID and Asthma/COPD Rehabilitees].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {78}, number = {2}, pages = {107-119}, doi = {10.1055/a-2215-3067}, pmid = {38190991}, issn = {1438-8790}, support = {Aktenzeichen 0421/40-64-50-74//Deutsche Rentenversicherung/ ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; *COVID-19 ; *Asthma ; *Pulmonary Disease, Chronic Obstructive/therapy ; Quality of Life ; }, abstract = {BACKGROUND: For some COVID-19 patients, symptoms and health impairments persist for an extended period of time (long COVID). Long-term consequences of the disease can lead to permanent limitations in participatory life. In these cases, medical rehabilitation may be useful. Due to the novelty of the disease, little is known about the need for rehabilitation and therapy and the health benefits of specific rehabilitation interventions.

METHODS: A multicentre longitudinal observational study was conducted. Persons affected by long COVID (LC) between 18 and 65 years of age undergoing pulmonary rehabilitation were included. An age-matched comparison group (CG) consisted of rehabilitation patients with bronchial asthma and COPD. Written questionnaires were administered at the beginning and end of rehabilitation, as well as six and twelve months after rehabilitation. Outcomes included parameters of subjective health, occupational outcomes, contents of rehabilitation and rehabilitation aftercare.

RESULTS: The sample consisted of 305 participants, of whom 172 were classified as LC and 133 as CG. In the total sample, one third of the participants were male and the average age was 53 years. All rehabilitation participants had high health burdens, LC patients had statistically significantly higher impairments in almost all outcomes recorded. At the beginning of rehabilitation, one third of the respondents were on sick leave, more often in LC than in the CG. Twelve months after rehabilitation, both groups achieved significant health improvement, with LC showing greater improvements in most outcomes (interaction effect p<0.01). Despite success in most parameters, LC patients still showed persistent COVID symptoms at twelve months. One year after rehabilitation, 89% returned to work.

CONCLUSION: The majority of rehabilitation patients benefit greatly from pulmonary medical rehabilitation in terms of health and occupation. The content of pulmonary rehabilitation seems to be suitable for this indication group; however, there is an indication-specific use of therapy between CG and LC group. As a result, the LC group seems to need more and different therapies.}, } @article {pmid38190281, year = {2024}, author = {Hung, CT and Hung, YC and Suk, CW}, title = {Prevalence and characteristics in long COVID among adults with asthma in the United States.}, journal = {The Journal of asthma : official journal of the Association for the Care of Asthma}, volume = {61}, number = {7}, pages = {736-744}, doi = {10.1080/02770903.2024.2303756}, pmid = {38190281}, issn = {1532-4303}, mesh = {Humans ; *Asthma/epidemiology ; United States/epidemiology ; Female ; Male ; *COVID-19/epidemiology ; Middle Aged ; Adult ; Prevalence ; Young Adult ; Aged ; SARS-CoV-2 ; Adolescent ; Age Factors ; Health Surveys ; Sex Factors ; Risk Factors ; }, abstract = {OBJECTIVE: The purpose of this study was to assess: (1) the prevalence of long COVID by asthma status, and (2) the characteristics associated with developing long COVID among adults with asthma in the United States.

METHODS: Data from the 2022 National Health Interview Survey were used. The prevalence of long COVID was reported and stratified by asthma status. The multivariable logistic regression model was conducted to identify the factors associated with developing long COVID.

RESULTS: In 2022, the overall prevalence of long COVID among U.S. adults was 6.9%. When stratified by asthma status, the prevalence of long COVID was 13.9% among adults with asthma, and 6.2% among adults without asthma. Among adults with asthma, certain characteristics, including age over 55 years, female sex, obesity, problems paying medical bills and a history of asthma attacks, were significantly associated with developing long COVID.

CONCLUSIONS: This study revealed that the prevalence of long COVID among adults with asthma was much higher than the general adult population in the United States. The limited validity of the collected information in this study should prompt caution when interpreting our findings. Further studies on the association between asthma and long COVID could be valuable for the clinical practice.}, } @article {pmid38188925, year = {2024}, author = {Hany, M and Sheta, E and Talha, A and Anwar, M and Selima, M and Gaballah, M and Zidan, A and Ibrahim, M and Agayby, ASS and Abouelnasr, AA and Samir, M and Torensma, B}, title = {Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination.}, journal = {Endoscopy international open}, volume = {12}, number = {1}, pages = {E11-E22}, pmid = {38188925}, issn = {2364-3722}, abstract = {Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination. Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins. Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P =0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups (P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort (P =0.002) and UGE subgroup (P =0.022), with a similar trend observed in the LGE subgroup (P =0.055). Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.}, } @article {pmid38188329, year = {2023}, author = {Martínez-Ayala, MC and Proaños, NJ and Cala-Duran, J and Lora-Mantilla, AJ and Cáceres-Ramírez, C and Villabona-Flórez, SJ and Camacho-López, PA}, title = {Factors associated with long COVID syndrome in a Colombian cohort.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1325616}, pmid = {38188329}, issn = {2296-858X}, abstract = {INTRODUCTION: After acute phase of SARS-CoV-2 infection, some patients persist with clinical symptoms, a phenomenon known as Long COVID syndrome. It is necessary to understand the factors associated with the persistence of these symptoms to develop individualized preventive approaches and effectively address this challenge.

OBJECTIVE: To determine the factors associated with the persistence of symptoms six months after COVID-19 infection.

MATERIALS AND METHODS: A ambidirectional cohort, single-center study, that included individuals previously diagnosed with COVID-19 by real-time polymerase chain reaction (PCR) positive test, who were followed for a period of six months. Univariate, bivariate and a multivariate binomial regression model were performed to determine risk factors associated with the persistence of COVID-19 symptoms at the six months of follow-up.

RESULTS: The prevalence of long COVID syndrome was 47%. Age demonstrated no significant association with Long COVID (RR 0.999 [95% CI 0.996-1.002]); however, female sex (RR 1.148 [95% CI 1.038-1.268]), requirement of mechanical ventilation (RR 1.278 [95% CI 1.050-1.555]), presence of Chronic Obstructive Pulmonary Disease (COPD) (RR 1.340 [95% CI 1.104-1.626]), Rheumatic Disease (RR 1.259 [95% CI 1.055-1.504]) and the Hospitalization Type: General Hospitalization (RR 1.247 [95% CI 1.090-1.427]) and ICU Hospitalization (RR 1.490 [95% CI 1.221-1.818]) were significantly associated with the persistence of symptoms at the six month of follow-up.

CONCLUSION: Female sex, presence of COPD, rheumatic disease, hospitalization type and requirement of mechanical ventilation during index infection were identified as significant risk factors for the diagnosis of Long COVID. These findings emphasize the importance of addressing Long COVID syndrome in terms of prevention and management, taking these risk factors into consideration.}, } @article {pmid38188200, year = {2023}, author = {Oleson, CV and Olsen, AC and Shermon, S}, title = {Spinal cord infarction attributed to SARS-CoV-2, with post-acute sequelae of COVID-19: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {36}, pages = {8542-8550}, pmid = {38188200}, issn = {2307-8960}, abstract = {BACKGROUND: While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spinal cord infarction or ischemia has been extremely rare. Findings of long coronavirus disease (COVID) in this select population have not been studied.

CASE SUMMARY: We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction, attributed to acute infection with SARS-CoV-2. Diagnostic work up confirmed a T3 complete (ASIA impairment Scale A) paraplegia resulting from a thrombotic infarct. Her reported myalgias, neuropathic pain, spasticity, bladder spasms, and urinary tract infections exceeded the frequency and severity of many spinal cord injury (SCI) individuals of similar age and degree of neurologic impairment. In her first year after contracting COVID-19, she underwent 2 separate inpatient rehabilitation courses, but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain. Yet other complications of complete non-traumatic SCI (NTSCI), including neurogenic bowel and temperature hypersensitivity, were mild, and pressure injuries were absent. She has now transitioned from the acute to chronic phase of spinal cord injury care, with subsequent development of post-acute sequelae of SARS-CoV-2 infection (PASC).

CONCLUSION: This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19, with subsequent progression to PASC.}, } @article {pmid38187378, year = {2023}, author = {Noonong, K and Chatatikun, M and Surinkaew, S and Kotepui, M and Hossain, R and Bunluepuech, K and Noothong, C and Tedasen, A and Klangbud, WK and Imai, M and Kawakami, F and Kubo, M and Kitagawa, Y and Ichikawa, H and Kanekura, T and Sukati, S and Somsak, V and Udomwech, L and Ichikawa, T and Nissapatorn, V and Tangpong, J and Indo, HP and Majima, HJ}, title = {Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1275001}, pmid = {38187378}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Reactive Oxygen Species ; Mitochondria ; Oxidative Stress ; }, abstract = {SIGNIFICANCE: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID.

RECENT ADVANCES: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease.

CRITICAL ISSUES: Patients who recover from COVID-19 can develop new or persistent symptoms of multi-organ complications lasting weeks or months, called long COVID. The underlying mechanisms involved in the long COVID is still unclear. Once the symptoms of long COVID persist, they cause significant damage, leading to numerous, persistent symptoms.

FUTURE DIRECTIONS: A comprehensive map of the stages and pathogenetic mechanisms related to long COVID and effective drugs to treat and prevent it are required, which will aid the development of future long COVID treatments and symptom relief.}, } @article {pmid38186472, year = {2023}, author = {Tariq Khan, S and Rashid, K and Ansar, F and Khan, MY and Ali Khan, F and Ebrahim Husain Ahmed Ali Ismaeel, R and Hanif Mohammed, R and Mustafa, R and Tariq Khan, B and Tariq, B and Husssain, M and Waheed, A}, title = {Long COVID-19 Syndrome: Insights From a Major Tertiary Center in the UK on Who Is at Greater Risk.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50027}, pmid = {38186472}, issn = {2168-8184}, abstract = {INTRODUCTION: The COVID-19 pandemic triggered the unprecedented 'long COVID' crisis, with persistent symptoms beyond two months post-infection. This study explores the nexus between long COVID symptoms, patient demographics such as age, gender, and smoking, and clinical factors like vaccination, disease severity, and comorbidities.

METHODS: A retrospective analysis of records was conducted between September 2021 and December 2022. The analysis covered adults with confirmed COVID-19 diagnoses. Data encompassed demographics, medical history, vaccination, disease severity, hospitalization, treatments, and post-COVID symptoms, analyzed using logistic regression.

RESULTS: Among 289 participants, the average age was 51.51 years. Around 62.6% were females, and 93% received the COVID-19 vaccination, i.e., primarily the mRNA vaccine (48.4%) and the adenovirus vector-based vaccine (34.8%). Reinfections occurred in 11.76% of cases. Disease severity varied, with 75% having mild, 15% having moderate, and 10% having severe infections. Hospitalization rates were significant (25.6%), including 10.7% requiring intensive care. Thirteen distinct post-COVID symptoms were reported. Fatigue, shortness of breath upon exertion, and brain fog emerged as the most prevalent symptoms. Notably, females exhibited higher symptom prevalence. Significant correlations were established between higher BMI and smoking with augmented symptomatology. Conversely, a link between booster doses and symptom reduction was discerned. Using multinomial regression analysis, gender and smoking were identified as predictors of post-COVID-19 symptoms.

CONCLUSION: The study underscores obesity, smoking, and the female gender's impact on long COVID symptoms; boosters show promise in alleviation. Respiratory pathology might underlie persistent symptoms in cases with radiological abnormalities and abnormal spirometry. Findings contribute to risk stratification, intervention strategies, and further research.}, } @article {pmid38186464, year = {2023}, author = {Mohan, N and Dalip, D and Jaggernauth, S}, title = {Organizing Pneumonia as a Pulmonary Sequela of Post-COVID-19 Syndrome in a Patient in Trinidad: A Case Report.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50148}, pmid = {38186464}, issn = {2168-8184}, abstract = {Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that commonly presents with exertional dyspnea. The mainstay diagnostic criterion is with histopathological confirmation alongside excluding secondary causes of interstitial lung disease. The COVID-19 pandemic left many mysteries regarding the long-term sequelae of this disease. We explore a case of post-COVID-19 syndrome organizing pneumonia (PCOP) in a patient presenting with new-onset respiratory symptoms seven weeks after recovery from COVID-19 infection. Upon further review of the literature, there were no published case reports on PCOP in Trinidad and Tobago. We describe a case of PCOP presented at Apley Medical Clinic, Trinidad, and Tobago, West Indies, with the aim of increasing awareness of this condition to allow for early identification and effective management.}, } @article {pmid38185937, year = {2024}, author = {Choi, CY and Gadhave, K and Villano, J and Pekosz, A and Mao, X and Jia, H}, title = {Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.}, journal = {Journal of medical virology}, volume = {96}, number = {1}, pages = {e29349}, pmid = {38185937}, issn = {1096-9071}, support = {R01 AG073291/AG/NIA NIH HHS/United States ; P50 AG005146/AG/NIA NIH HHS/United States ; 1R01AI148446-01A1/GF/NIH HHS/United States ; 1R2AI14932101/GF/NIH HHS/United States ; P50 AG05146/GF/NIH HHS/United States ; R21 AI149321/AI/NIAID NIH HHS/United States ; R01 AI148446/AI/NIAID NIH HHS/United States ; 3R21AI149321-01S1/GF/NIH HHS/United States ; R01AG073291/GF/NIH HHS/United States ; P30 NS050274/NS/NINDS NIH HHS/United States ; R01 NS107318/NS/NINDS NIH HHS/United States ; R01NS107318/GF/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Young Adult ; Angiotensin-Converting Enzyme 2/genetics ; *COVID-19 ; Disease Models, Animal ; Disease Progression ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 10[5] PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.}, } @article {pmid38185377, year = {2024}, author = {Rischard, F and Altman, N and Szmuszkovicz, J and Sciurba, F and Berman-Rosenzweig, E and Lee, S and Krishnan, S and Truong, N and Wood, J and Finn, AV and , }, title = {Long-Term Effects of COVID-19 on the Cardiopulmonary System in Adults and Children: Current Status and Questions to be Resolved by the National Institutes of Health Researching COVID to Enhance Recovery Initiative.}, journal = {Chest}, volume = {165}, number = {4}, pages = {978-989}, pmid = {38185377}, issn = {1931-3543}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; United States/epidemiology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Dyspnea ; Lung ; }, abstract = {TOPIC IMPORTANCE: Long COVID may occur in at least 10% of patients recovering from SARS-CoV-2 infection and often is associated with debilitating symptoms. Among the organ systems that might be involved in its pathogenesis, the respiratory and cardiovascular systems may be central to common symptoms seen in survivors of COVID-19, including fatigue, dyspnea, chest pain, cough, and exercise intolerance. Understand the exact symptomatology, causes, and effects of long COVID on the heart and lungs may help us to discover new therapies. To that end, the National Institutes of Health is sponsoring a national study population of diverse volunteers to support large-scale studies on the long-term effects of COVID-19.

REVIEW FINDINGS: The National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative currently is recruiting participants in the United States to answer critical questions about long COVID. The study comprises adult and pediatric cohorts as well as an electronic health record cohort. Based on symptoms, individuals undergo prespecified medical testing to understand whether abnormalities can be detected and are followed up longitudinally. Herein, we outline current understanding of the clinical symptoms and pathophysiologic features of long COVID with respect to the cardiopulmonary system in adults and children and then determine how the clinical, electronic health record, and autopsy cohorts of the RECOVER initiative will attempt to answer the most pressing questions surrounding the long-term effects of COVID-19.

SUMMARY: Data generated from the RECOVER initiative will provide guidance about missing gaps in our knowledge about long COVID and how they might be filled by data gathered through the RECOVER initiative.}, } @article {pmid38185275, year = {2024}, author = {Margalit, I and Yahav, D}, title = {The potential role of vagus nerve dysfunction and dysautonomia in long COVID.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {4}, pages = {423-427}, doi = {10.1016/j.cmi.2024.01.001}, pmid = {38185275}, issn = {1469-0691}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Autonomic Nervous System Diseases ; Vagus Nerve ; }, } @article {pmid38183882, year = {2024}, author = {van den Houdt, SCM and Slurink, IAL and Mertens, G}, title = {Long COVID is not a uniform syndrome: Evidence from person-level symptom clusters using latent class analysis.}, journal = {Journal of infection and public health}, volume = {17}, number = {2}, pages = {321-328}, doi = {10.1016/j.jiph.2023.12.019}, pmid = {38183882}, issn = {1876-035X}, mesh = {Humans ; Male ; Young Adult ; Adult ; Middle Aged ; Female ; Latent Class Analysis ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cluster Analysis ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The current study aims to enhance insight into the heterogeneity of long COVID by identifying symptom clusters and associated socio-demographic and health determinants.

METHODS: A total of 458 participants (Mage 36.0 ± 11.9; 46.5% male) with persistent symptoms after COVID-19 completed an online self-report questionnaire including a 114-item symptom list. First, a k-means clustering analysis was performed to investigate overall clustering patterns and identify symptoms that provided meaningful distinctions between clusters. Next, a step-three latent class analysis (LCA) was performed based on these distinctive symptoms to analyze person-centered clusters. Finally, multinominal logistic models were used to identify determinants associated with the symptom clusters.

RESULTS: From a 5-cluster solution obtained from k-means clustering, 30 distinctive symptoms were selected. Using LCA, six symptom classes were identified: moderate (20.7%) and high (20.7%) inflammatory symptoms, moderate malaise-neurocognitive symptoms (18.3%), high malaise-neurocognitive-psychosocial symptoms (17.0%), low-overall symptoms (13.3%) and high overall symptoms (9.8%). Sex, age, employment, COVID-19 suspicion, COVID-19 severity, number of acute COVID-19 symptoms, long COVID symptom duration, long COVID diagnosis, and impact of long COVID were associated with the different symptom clusters.

CONCLUSIONS: The current study's findings characterize the heterogeneity in long COVID symptoms and underscore the importance of identifying determinants of different symptom clusters.}, } @article {pmid38180084, year = {2024}, author = {Dhanushkodi, NR and Prakash, S and Quadiri, A and Zayou, L and Srivastava, R and Shaik, AM and Suzer, B and Ibraim, IC and Landucci, G and Tifrea, DF and Singer, M and Jamal, L and Edwards, RA and Vahed, H and Brown, L and BenMohamed, L}, title = {Antiviral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {212}, number = {4}, pages = {576-585}, doi = {10.4049/jimmunol.2300392}, pmid = {38180084}, issn = {1550-6606}, support = {AI158060//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI150091//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI143348//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI147499//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI143326//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI138764//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI124911//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI110902//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; AI174383//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; }, mesh = {Cricetinae ; Humans ; Mice ; Animals ; *SARS-CoV-2 ; Mesocricetus ; *COVID-19 ; Receptor for Advanced Glycation End Products/genetics ; Post-Acute COVID-19 Syndrome ; Mice, Transgenic ; Antiviral Agents/pharmacology/therapeutic use ; Disease Models, Animal ; Lung ; *gamma-Globulins ; *Melphalan ; }, abstract = {SARS-CoV-2 variants of concern (VOCs) continue to evolve and reemerge with chronic inflammatory long COVID sequelae, necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the receptor for advanced glycation end products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an antiviral and anti-inflammatory therapeutic effect in the COVID-19 system. The protective therapeutic effect of RAGE-Ig was determined in vivo in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six VOCs of SARS-CoV-2. The underlying antiviral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated (1) significant dose-dependent protection (i.e., greater survival, less weight loss, lower virus replication in the lungs); (2) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (3) a RAGE-Ig dose-dependent increase in the expression of type I IFNs (IFN-α and IFN-β) and type III IFN (IFNλ2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (4) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Our preclinical findings revealed type I and III IFN-mediated antiviral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.}, } @article {pmid38179898, year = {2024}, author = {Feinman, J and Parikh, A and Behar, J and Ashley, K and Lala, A and Moss, N and Natelson, B and Mancini, D}, title = {Incidence of long CoVid 19 among heart transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {26}, number = {1}, pages = {e14218}, doi = {10.1111/tid.14218}, pmid = {38179898}, issn = {1399-3062}, mesh = {Humans ; Incidence ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Heart Transplantation/adverse effects ; *Kidney Transplantation ; Transplant Recipients ; }, } @article {pmid38179211, year = {2024}, author = {Benis, D and Voruz, P and Chiuve, SC and Garibotto, V and Assal, F and Krack, P and Péron, J and Fleury, V}, title = {Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection.}, journal = {Case reports in neurology}, volume = {16}, number = {1}, pages = {6-17}, pmid = {38179211}, issn = {1662-680X}, abstract = {INTRODUCTION: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

CASE PRESENTATION: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

CONCLUSION: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.}, } @article {pmid38178969, year = {2023}, author = {Collier, D and Garip, G}, title = {The hidden pandemic: a qualitative study on how middle-aged women make sense of managing their long COVID symptoms.}, journal = {Health psychology report}, volume = {11}, number = {4}, pages = {269-281}, pmid = {38178969}, issn = {2353-5571}, abstract = {BACKGROUND: A relapsing and remitting illness, long COVID can be challenging and debilitating. A person living with long COVID can feel like they are getting better and recovering only to relapse again. The aim of the research was to explore how non-hospitalized middle-aged women who contracted COVID in the first wave of the pandemic, from March 2020, are managing their long COVID symptoms.

PARTICIPANTS AND PROCEDURE: A qualitative research study with an interpretative phenomenological analysis approach was used to explore how the women made sense of managing their condition and health seeking behaviours. Participants were recruited from long COVID Facebook groups and semi-structured interviews were conducted remotely by Teams audio; these were digitally recorded and transcribed by hand with prior informed consent. Nine women were interviewed and four themes and eight sub-themes emerged from the data.

RESULTS: The four emerging themes were: inequality and inconsistent medical treatment; uncertainty and ambiguity of managing long COVID symptoms; managing other people's expectations and perceptions of long COVID; and the changing identity. Overall, these results indicated a general mistrust in health care services to provide adequate support and individualized treatment plans leading women to self-advocacy and to seek alternative support and treatment.

CONCLUSIONS: This study raised questions about the possible unfair treatment of women seeking medical attention for their long COVID symptoms; how ambiguous symptoms are misattributed to anxiety and discrimination from health care professionals contributes towards stigma. The study concludes with recommendations for service improvement such as the compassionate validation of patients' pain and the use of evidence-based therapeutic practices such as mindfulness.}, } @article {pmid38177896, year = {2024}, author = {Hildebrandt, ME and Møller, PR and Fjældstad, AW and Ovesen, T}, title = {Postinfectious conditions challenge disease-specificity of SNOT-22.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {281}, number = {5}, pages = {2395-2402}, pmid = {38177896}, issn = {1434-4726}, mesh = {Humans ; Chronic Disease ; *COVID-19/complications ; Quality of Life ; Retrospective Studies ; *Rhinitis/complications/diagnosis ; Sino-Nasal Outcome Test ; *Sinusitis/complications/diagnosis ; }, abstract = {PURPOSE: The Sino-Nasal-Outcome-Test 22 (SNOT-22) questionnaire assesses treatment outcome and health-related quality of life (HRQOL) in patients with chronic rhinosinusitis (CRS). However, given the overlap between CRS and olfaction in terms of nasal function and the definition of CRS, a fundamental question arises: can patients with olfactory dysfunction (OD) stemming from other causes attain SNOT-22 scores similar to those seen in CRS, even in the absence of CRS? Our study aimed to explore whether OD arising from various postinfectious mechanisms challenges the disease-specificity of SNOT-22 for CRS. If so, could focus on scores within specific symptom domains of SNOT-22 prove valuable in distinguishing between different etiologies.

METHODS: The study adopted an observational, retrospective cohort design based on prospectively registered patients and related variables using the REDCap platform. 460 patients experiencing OD due to either (1) simple or (2) complex post-COVID-19, (3) postinfectious non-COVID-19, and (4) CRS, were included in the analysis.

RESULTS: The study revealed that the total SNOT-22 score lacks disease-specificity for CRS. This is evident, because complex postinfectious mechanisms resulting from COVID-19 can produce similar symptoms in patients. Notably, elevated total scores were primarily driven by high subdomain scores within the "sleep and cognition" domain.

CONCLUSIONS: The application of SNOT-22 as a screening tool needs to be approached with caution, as the total score alone does not provide disease-specific insights. A more thorough exploration of the four symptom domains and the identification of distinctive scoring patterns within the clinical context may prove pivotal in effectively differentiating between various underlying causes.}, } @article {pmid38177128, year = {2024}, author = {Appelman, B and Charlton, BT and Goulding, RP and Kerkhoff, TJ and Breedveld, EA and Noort, W and Offringa, C and Bloemers, FW and van Weeghel, M and Schomakers, BV and Coelho, P and Posthuma, JJ and Aronica, E and Joost Wiersinga, W and van Vugt, M and Wüst, RCI}, title = {Muscle abnormalities worsen after post-exertional malaise in long COVID.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {17}, pmid = {38177128}, issn = {2041-1723}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Case-Control Studies ; *COVID-19/complications ; Fatigue/etiology ; *Musculoskeletal Abnormalities ; Muscle, Skeletal ; Pain ; Plaque, Amyloid ; }, abstract = {A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.}, } @article {pmid38177028, year = {2024}, author = {Rodriguez, L and Brodin, P}, title = {Immune system perturbations in patients with long COVID.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {200-201}, doi = {10.1016/j.molmed.2023.12.008}, pmid = {38177028}, issn = {1471-499X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19 ; Immune System ; }, abstract = {Klein et al. report multimodal analyses of immune cells, proteins, and physiological parameters in patients with long COVID (LC). At the group level, LC subjects exhibited elevated antibody responses to SARS-CoV-2, but also to herpes viruses, pointing to a general suppression of viral control mechanisms in LC.}, } @article {pmid38176975, year = {2024}, author = {Finch, F and Parker, P and Nollett, C and Burns, S}, title = {The novel application of the Lightning Process to treat Long COVID in primary care - Case report.}, journal = {Explore (New York, N.Y.)}, volume = {20}, number = {2}, pages = {248-252}, doi = {10.1016/j.explore.2023.08.009}, pmid = {38176975}, issn = {1878-7541}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/therapy ; *Fatigue Syndrome, Chronic/therapy/diagnosis/psychology ; Primary Health Care ; }, abstract = {As a result of the COVID-19 pandemic, Long COVID (LC) is now prevalent in many countries. Little evidence exists regarding how this chronic condition should be treated, but guidelines suggest for most people it can be managed symptomatically in primary care. The Lightning Process is a trademarked positive psychology focused self-management programme which has shown to be effective in reducing fatigue and accompanying symptoms in other chronic conditions including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Here we outline its novel application to two patients with LC who both reported improvements in fatigue and a range of physical and emotional symptoms post-treatment and at 3 months follow-up.}, } @article {pmid38176902, year = {2024}, author = {Freedman, MB and Kim, YJ and Kaur, R and Jain, BV and Adegunsoye, AO and Chung, YC and DeLisa, JA and Gardner, JM and Gordon, HS and Greenberg, JA and Kaul, M and Khouzam, N and Labedz, SL and Mokhlesi, B and Rintz, J and Rubinstein, I and Taylor, A and Vines, DL and Ziauddin, L and Gerald, LB and Krishnan, JA}, title = {Home Oxygen After Hospitalization for COVID-19: Results From the Multi-Center OXFORD Study.}, journal = {Respiratory care}, volume = {69}, number = {3}, pages = {281-289}, pmid = {38176902}, issn = {1943-3654}, support = {T32 HL144909/HL/NHLBI NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/therapy ; SARS-CoV-2 ; Retrospective Studies ; Cohort Studies ; Hospitalization ; Oxygen ; Adrenal Cortex Hormones ; }, abstract = {BACKGROUND: In the first months of the pandemic, prior to the introduction of proven-effective treatments, 15-37% of patients hospitalized with COVID-19 were discharged on home oxygen. After proven-effective treatments for acute COVID-19 were established by evidence-based guidelines, little remains known about home oxygen requirements following hospitalization for COVID-19.

METHODS: This was a retrospective, multi-center cohort study of subjects hospitalized for COVID-19 between October 2020-September 2021 at 3 academic health centers. Information was abstracted from electronic health records at the index hospitalization and for 60 d after discharge. The World Health Organization COVID-19 Clinical Progression Scale score was used to identify patients with severe COVID-19.

RESULTS: Of 517 subjects (mean age 58 y, 47% female, 42% Black, 36% Hispanic, 22% with severe COVID-19), 81% were treated with systemic corticosteroids, 61% with remdesivir, and 2.5% with tocilizumab. About one quarter of subjects were discharged on home oxygen (26% [95% CI 22-29]). Older age (adjusted odds ratio [aOR] 1.02 per 5 y [95% CI 1.02-1.02]), higher body mass index (aOR 1.02 per kg/m[2] [1.00-1.04]), diabetes (yes vs no, aOR 1.73 [1.46-2.02]), severe COVID-19 (vs moderate, aOR 3.19 [2.19-4.64]), and treatment with systemic corticosteroids (yes vs no, aOR 30.63 [4.51-208.17]) were associated with an increased odds of discharge on home oxygen. Comorbid hypertension (yes vs no, aOR 0.71 [0.66-0.77) was associated with a decreased odds of home oxygen. Within 60 d of hospital discharge, 50% had documentation of pulse oximetry; in this group, home oxygen was discontinued in 46%.

CONCLUSIONS: About one in 4 subjects were prescribed home oxygen after hospitalization for COVID-19, even after guidelines established proven-effective treatments for acute illness. Evidence-based strategies to reduce the requirement for home oxygen in patients hospitalized for COVID-19 are needed.}, } @article {pmid38175151, year = {2024}, author = {Durstenfeld, MS and Peluso, MJ and Lin, F and Peyser, ND and Isasi, C and Carton, TW and Henrich, TJ and Deeks, SG and Olgin, JE and Pletcher, MJ and Beatty, AL and Marcus, GM and Hsue, PY}, title = {Association of nirmatrelvir for acute SARS-CoV-2 infection with subsequent Long COVID symptoms in an observational cohort study.}, journal = {Journal of medical virology}, volume = {96}, number = {1}, pages = {e29333}, pmid = {38175151}, issn = {1096-9071}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; /PCORI/Patient-Centered Outcomes Research Institute/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Ritonavir ; Cohort Studies ; SARS-CoV-2 ; }, abstract = {Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants. We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March-August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female. At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80-1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74-2.41; p = 0.33). Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection.}, } @article {pmid38174103, year = {2024}, author = {Kantele, A and Paajanen, J and Pietilä, JP and Vapalahti, O and Pakkanen, SH and Lääveri, T}, title = {Long COVID-associated symptoms prevalent in both SARS-CoV-2 positive and negative individuals: A prospective follow-up study.}, journal = {New microbes and new infections}, volume = {56}, number = {}, pages = {101209}, pmid = {38174103}, issn = {2052-2975}, abstract = {BACKGROUND: Research into persistent symptoms among SARS-CoV-2-positive i.e. CoV(+) patients mostly focuses on hospitalized individuals. Our prospective follow-up study compares long COVID-associated symptoms among laboratory-confirmed CoV(+) and SARS-CoV-2 negative [CoV(-)] individuals.

METHODS: SARS-CoV-2 RT-PCR-tested volunteers were recruited into four cohorts: 1) CoV(+) outpatients, 2) CoV(-) outpatients, 3) CoV(+) intensive care unit (ICU) inpatients, and 4) CoV(+) non-ICU inpatients. Neutralizing antibodies were assessed and questionnaires filled in at enrolment and days 90-120, 121-180, 181-270, 271-365, and 365-533.

RESULTS: Of the 1326 participants, 1191 were CoV(+): 46 ICU, 123 non-ICU, and 1022 outpatients; 135 were CoV(-) outpatient controls. Both CoV(+) outpatients and CoV(-) controls showed high overall symptom rates at all time points. More prevalent among CoV(+) than CoV(-) outpatients were only impaired olfaction and taste; many others proved more frequent for CoV(-) participants. At ≥181 days, fatigue, dyspnoea, various neuropsychological symptoms and several others were recorded more often for CoV(+) inpatients than outpatients.

CONCLUSIONS: Long COVID-associated symptoms were more frequent among hospitalized than non-hospitalized CoV(+) participants. As for outpatients, only impaired olfaction and taste showed higher rates in the CoV(+) group; some symptoms proved even more common among those CoV(-). Besides suggesting low long COVID prevalences for outpatients, our results highlight the weight of negative controls.}, } @article {pmid38173949, year = {2024}, author = {Mogitate, M}, title = {Differences Between Patients With Chronic Epipharyngitis With and Without Previous COVID-19 Infection.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e51543}, pmid = {38173949}, issn = {2168-8184}, abstract = {Objective Epipharyngeal abrasive therapy (EAT) is effective in patients with chronic epipharyngitis who previously had coronavirus disease 2019 (COVID-19). The study aimed to evaluate differences between patients with chronic epipharyngitis with (long COVID) or without a history of COVID-19 (non-long COVID). Methods This is a retrospective study based on the analysis of medical records of patients who visited the Mogitate ENT Clinic in Kawasaki, Japan, for six months from March 2022. Results Patients with long COVID were significantly younger (p=0.018). Fatigue and brain fog were prevalent in patients with long COVID, whereas throat discomfort, postnasal drip, and sputum were more common in those with non-long COVID. Epipharyngeal endoscopic findings in patients with long COVID showed significantly higher scores (p<0.001) compared with patients with non-long COVID. Conclusions The primary differences between patients with long COVID and non-long COVID were age, symptoms, and severity scores of endoscopic findings. The EAT should be aggressively implemented in patients with chronic epipharyngitis with or without COVID-19 infection, as there is no reason not to treat a patient with a condition caused by COVID-19 infection.}, } @article {pmid38172612, year = {2024}, author = {Rubas, NC and Peres, R and Kunihiro, BP and Allan, NP and Phankitnirundorn, K and Wells, RK and McCracken, T and Lee, RH and Umeda, L and Conching, A and Juarez, R and Maunakea, AK}, title = {HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {355}, pmid = {38172612}, issn = {2045-2322}, support = {R01 MD016593/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Disease Progression ; *HMGB1 Protein/genetics ; Longitudinal Studies ; *Microbiota ; Obesity/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.}, } @article {pmid38172361, year = {2024}, author = {Ledford, H}, title = {Long COVID is a double curse in low-income nations - here's why.}, journal = {Nature}, volume = {625}, number = {7993}, pages = {20-22}, pmid = {38172361}, issn = {1476-4687}, mesh = {Humans ; *Attitude of Health Personnel ; *Developing Countries/economics ; *Health Knowledge, Attitudes, Practice ; Physicians ; *Post-Acute COVID-19 Syndrome/economics/therapy ; }, } @article {pmid38172332, year = {2024}, author = {Helbing, DL and Dommaschk, EM and Danyeli, LV and Liepinsh, E and Refisch, A and Sen, ZD and Zvejniece, L and Rocktäschel, T and Stabenow, LK and Schiöth, HB and Walter, M and Dambrova, M and Besteher, B}, title = {Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1829-1845}, pmid = {38172332}, issn = {1433-8491}, support = {857394 (FAT4BRAIN)//Horizon 2020 Framework Programme/ ; }, mesh = {Humans ; *Acetylcarnitine/pharmacology/therapeutic use ; *COVID-19/complications ; *Dietary Supplements ; *Post-Acute COVID-19 Syndrome ; Fatigue Syndrome, Chronic/drug therapy ; }, abstract = {Post-acute sequelae of COVID-19 can present as multi-organ pathology, with neuropsychiatric symptoms being the most common symptom complex, characterizing long COVID as a syndrome with a significant disease burden for affected individuals. Several typical symptoms of long COVID, such as fatigue, depressive symptoms and cognitive impairment, are also key features of other psychiatric disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and major depressive disorder (MDD). However, clinically successful treatment strategies are still lacking and are often inspired by treatment options for diseases with similar clinical presentations, such as ME/CFS. Acetylcarnitine, the shortest metabolite of a class of fatty acid metabolites called acylcarnitines and one of the most abundant blood metabolites in humans can be used as a dietary/nutritional supplement with proven clinical efficacy in the treatment of MDD, ME/CFS and other neuropsychiatric disorders. Basic research in recent decades has established acylcarnitines in general, and acetylcarnitine in particular, as important regulators and indicators of mitochondrial function and other physiological processes such as neuroinflammation and energy production pathways. In this review, we will compare the clinical basis of neuropsychiatric long COVID with other fatigue-associated diseases. We will also review common molecular disease mechanisms associated with altered acetylcarnitine metabolism and the potential of acetylcarnitine to interfere with these as a therapeutic agent. Finally, we will review the current evidence for acetylcarnitine as a supplement in the treatment of fatigue-associated diseases and propose future research strategies to investigate the potential of acetylcarnitine as a treatment option for long COVID.}, } @article {pmid38171599, year = {2024}, author = {Mariette, X}, title = {Response to: Correspondence on 'Long COVID: a new word for naming fibromyalgia?" by Mariette.}, journal = {Annals of the rheumatic diseases}, volume = {83}, number = {7}, pages = {e16}, doi = {10.1136/ard-2023-225316}, pmid = {38171599}, issn = {1468-2060}, mesh = {*Fibromyalgia ; Humans ; *COVID-19/complications ; *Terminology as Topic ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38171597, year = {2024}, author = {Landewé, RBM}, title = {Correspondence on 'Long COVID: a new word for naming fibromyalgia?' by Mariette.}, journal = {Annals of the rheumatic diseases}, volume = {83}, number = {7}, pages = {e15}, doi = {10.1136/ard-2023-225309}, pmid = {38171597}, issn = {1468-2060}, mesh = {Humans ; *Fibromyalgia ; *COVID-19/complications ; *Terminology as Topic ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38169007, year = {2024}, author = {Munro, APS and Jones, CE and Faust, SN}, title = {Vaccination against COVID-19 - risks and benefits in children.}, journal = {European journal of pediatrics}, volume = {183}, number = {3}, pages = {1107-1112}, pmid = {38169007}, issn = {1432-1076}, mesh = {Adolescent ; Adult ; Child ; Humans ; Male ; *COVID-19/prevention & control/complications ; *COVID-19 Vaccines/adverse effects ; *Myocarditis/etiology ; Risk Assessment ; SARS-CoV-2 ; Syndrome ; *Systemic Inflammatory Response Syndrome ; Vaccination/adverse effects ; }, abstract = {Countries in Europe and around the world have taken varying approaches to their policies on COVID-19 vaccination for children. The low risk of severe illness from COVID-19 means that even small risks from vaccination warrant careful consideration. Vaccination appears to result in a decreased risk of severe illness including the paediatric multi-system inflammatory syndrome known to be associated with COVID-19. These risks have already decreased significantly with the emergence of the Omicron variant and its subvariants, and due to widespread population immunity through previous infection. There is a relatively high risk of myocarditis following second doses of mRNA vaccines in adolescent males, although the general course of this condition appears mild. Conclusion: COVID-19 vaccination only provides a transient reduction in transmission. Currently, insufficient evidence exists to determine the impact of vaccination on post-acute COVID syndromes in children, which are uncommon. What is Known: • Vaccines against COVID-19 have significantly reduced morbidity and mortality around the world. • Whilst countries have universally recommended vaccines for adults and continue to recommend them for vulnerable populations, there has been more variability in recommendations for children. What is New: • In the setting of near universal existing immunity from infection, the majority of the initial benefit in protecting against severe illness has been eroded. • The risks of myocarditis following mRNA vaccination for children is low, but an important consideration given the modest benefits.}, } @article {pmid38168099, year = {2024}, author = {Somayajula, SA and Litake, O and Liang, Y and Hosseini, R and Nemati, S and Wilson, DO and Weinreb, RN and Malhotra, A and Xie, P}, title = {Improving long COVID-related text classification: a novel end-to-end domain-adaptive paraphrasing framework.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {85}, pmid = {38168099}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Pandemics ; Machine Learning ; Health Personnel ; }, abstract = {The emergence of long COVID during the ongoing COVID-19 pandemic has presented considerable challenges for healthcare professionals and researchers. The task of identifying relevant literature is particularly daunting due to the rapidly evolving scientific landscape, inconsistent definitions, and a lack of standardized nomenclature. This paper proposes a novel solution to this challenge by employing machine learning techniques to classify long COVID literature. However, the scarcity of annotated data for machine learning poses a significant obstacle. To overcome this, we introduce a strategy called medical paraphrasing, which diversifies the training data while maintaining the original content. Additionally, we propose a Data-Reweighting-Based Multi-Level Optimization Framework for Domain Adaptive Paraphrasing, supported by a Meta-Weight-Network (MWN). This innovative approach incorporates feedback from the downstream text classification model to influence the training of the paraphrasing model. During the training process, the framework assigns higher weights to the training examples that contribute more effectively to the downstream task of long COVID text classification. Our findings demonstrate that this method substantially improves the accuracy and efficiency of long COVID literature classification, offering a valuable tool for physicians and researchers navigating this complex and ever-evolving field.}, } @article {pmid38166755, year = {2024}, author = {Pham, HT and Mai-Phan, TA and Truong-Nguyen, KH and Tran, MH}, title = {Effects of antivirals on patients with COVID-19 breakthrough.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {25}, pmid = {38166755}, issn = {1471-2334}, mesh = {Adult ; Retrospective Studies ; Antiviral Agents/therapeutic use ; Breakthrough Infections ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Middle Aged ; }, abstract = {BACKGROUND: Antivirals have been given widely for patients with COVID-19 breakthrough in Asian countries, creating a "black market" for unapproved and unprescribed medications. More evidence is needed to clarify the benefits of antivirals in these settings.

METHODS: We conducted a random-sampling retrospective cohort study at a general hospital in Vietnam. We recruited patients with mild-to-moderate COVID-19 breakthrough who were given either standard of care (SoC) alone or SoC + antiviral. Primary outcome was residual respiratory symptoms that lasted > 7 days. Secondary outcome was long COVID-19, diagnosed by specialized physicians. We used logistic regression to measure odds ratio (OR), in addition to a sensitivity and subgroup analyses to further explore the results.

RESULTS: A total of 142 patients (mean age 36.2 ± 9.8) were followed. We recorded residual symptoms in 27.9% and 20.3% of the SoC and SoC + antiviral group, while the figures for long COVID-19 were 11.8% and 8.1%, respectively. Antiviral use was not significantly associated with lower the risks of residual symptoms (OR = 0.51, 95% CI: 0.22-1.20, p = 0.12) or long COVID-19 (OR = 0.55, 95% CI: 0.16-1.90, p = 0.35). The sensitivity and subgroup analyses did not show any significant differences between the study groups (all p > 0.05).

CONCLUSION: Antivirals were not associated with faster resolution of respiratory symptoms or lower risks of long COVID-19. Further studies should focus on different antivirals to confirm their effects on different sub-populations. Meanwhile, antivirals should only be used in very high-risk patients to avoid excessive costs and harms.}, } @article {pmid38166694, year = {2024}, author = {Shang, H and Chang, T and Yang, W and Shi, L and Hu, S and Tian, L and Ren, J and Wang, T and Wang, J and Guo, J and Cui, Y}, title = {Analysis of influencing factors on long COVID in COVID-19 patients infected with omicron variant three months after discharge: a cross-sectional study.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {36}, pmid = {38166694}, issn = {1471-2334}, mesh = {Adult ; Female ; Humans ; Male ; Amnesia ; Cough ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Cross-Sectional Studies ; Fatigue ; Fever/epidemiology ; Patient Discharge ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Sleep Initiation and Maintenance Disorders ; Middle Aged ; }, abstract = {BACKGROUND: The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022.

METHODS: In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID.

RESULTS: A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425-0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086-2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501-0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190-1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases).

CONCLUSION: The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.}, } @article {pmid38164831, year = {2023}, author = {Liu, YZ and Jiang, T and Jiang, CL}, title = {Bioinformatic analysis identified common pathogenetic processes between epilepsy and COVID-19.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {24}, pages = {11673-11690}, doi = {10.26355/eurrev_202312_34765}, pmid = {38164831}, issn = {2284-0729}, mesh = {Humans ; *COVID-19/genetics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Epilepsy/genetics ; Seizures ; Computational Biology ; }, abstract = {OBJECTIVE: With the ongoing progression of SARS-CoV-2-induced COVID-19, the post-acute COVID-19 syndrome (long COVID) has garnered increasing attention as a novel multisystem disorder. Long COVID-19 has been shown to impact the nervous system, leading to various neurological manifestations, including epilepsy and seizures. Current studies have reported a significant increase in the prevalence and mortality rate of epilepsy in COVID-19 patients. Additionally, COVID-19 exacerbates seizures in patients with epilepsy. However, the mechanisms underlying the impact of COVID-19 on epilepsy remain elusive. This research focused on further identifying and elucidating the molecular mechanisms and biological processes underlying the induction of epilepsy by COVID-19 through bioinformatic methods.

MATERIALS AND METHODS: We retrieved four gene expression datasets related to COVID-19 and epilepsy patients from the GEO and ArrayExpress databases. By crossing the major modules of weighted gene co-expression network analysis (WGCNA), the commonly expressed genes of epilepsy and COVID-19 were identified. By establishing the protein-protein interaction (PPI) network of the common genes, 20 hub genes were recognized through CytoHubba. Furthermore, functional enrichment and immune cell infiltration analyses were conducted to explore the potential mechanisms of COVID-19-related epilepsy.

RESULTS: We identified a total of 373 common genes between the two diseases. The functional enrichment analysis revealed that the common genes were mainly involved in biological processes related to the immune response. Further analysis of the Hub genes revealed the important role of abnormal lipid metabolism in the crosstalk between COVID-19 and epilepsy. LASSO regression identified CD38 and PRKCA as the potential shared diagnostic candidates, which also exhibited excellent diagnostic value in the validation dataset. The immune infiltration analysis showed that activated dendritic cells (DCs) were positively correlated with the phenotypes of both diseases.

CONCLUSIONS: This research revealed the potential mechanisms of COVID-19-related epilepsy, providing novel insights for the prevention, diagnosis, and clinical management strategies of COVID-19-related epilepsy.}, } @article {pmid38163814, year = {2024}, author = {Fedorowski, A and Fanciulli, A and Raj, SR and Sheldon, R and Shibao, CA and Sutton, R}, title = {Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden.}, journal = {Nature reviews. Cardiology}, volume = {21}, number = {6}, pages = {379-395}, pmid = {38163814}, issn = {1759-5010}, mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; *Autonomic Nervous System Diseases/physiopathology/etiology/diagnosis ; *Cardiovascular Diseases/physiopathology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.}, } @article {pmid38163173, year = {2024}, author = {Harriott, NC and Ryan, AL}, title = {Proteomic profiling identifies biomarkers of COVID-19 severity.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23320}, pmid = {38163173}, issn = {2405-8440}, support = {P30 DK054759/DK/NIDDK NIH HHS/United States ; }, abstract = {SARS-CoV-2 infection remains a major public health concern, particularly for the aged and those individuals with co-morbidities at risk for developing severe COVID-19. Understanding the pathogenesis and biomarkers associated with responses to SARS-CoV-2 infection remain critical components in developing effective therapeutic approaches, especially in cases of severe and long-COVID-19. In this study blood plasma protein expression was compared in subjects with mild, moderate, and severe COVID-19 disease. Evaluation of an inflammatory protein panel confirms upregulation of proteins including TNFβ, IL-6, IL-8, IL-12, already associated with severe cytokine storm and progression to severe COVID-19. Importantly, we identify several proteins not yet associated with COVID-19 disease, including mesothelin (MSLN), that are expressed at significantly higher levels in severe COVID-19 subjects. In addition, we find a subset of markers associated with T-cell and dendritic cell responses to viral infection that are significantly higher in mild cases and decrease in expression as severity of COVID-19 increases, suggesting that an immediate and effective activation of T-cells is critical in modulating disease progression. Together, our findings identify new targets for further investigation as therapeutic approaches for the treatment of SARS-CoV-2 infection and prevention of complications of severe COVID-19.}, } @article {pmid38162880, year = {2023}, author = {Pagen, DME and Van Herck, M and van Bilsen, CJA and Brinkhues, S and Konings, K and den Heijer, CDJ and Spruit, MA and Hoebe, CJPA and Dukers-Muijrers, NHTM}, title = {High proportions of post-exertional malaise and orthostatic intolerance in people living with post-COVID-19 condition: the PRIME post-COVID study.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1292446}, pmid = {38162880}, issn = {2296-858X}, abstract = {BACKGROUND: Exercise-based treatments can worsen/exacerbate symptoms in people who were SARS-CoV-2 positive and living with post-COVID-19 condition (PL-PCC) and who have post-exertional malaise (PEM) or orthostatic intolerance (OI). Nevertheless, PEM and OI are not routinely assessed by clinicians. We estimated PEM and OI proportions in PL-PCC, as well as in people not living with PCC (PnL-PCC) and negatives (i.e., never reported a SARS-CoV-2 positive test), and identified associated factors.

METHODS: Participants from the Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study were included. PEM and OI were assessed using validated questionnaires. PCC was defined as feeling unrecovered after SARS-CoV-2 infection. Multivariable regression analyses to study PEM and OI were stratified for sex.

RESULTS: Data from 3,783 participants were analyzed. In PL-PCC, the proportion of PEM was 48.1% and 41.2%, and the proportion of OI was 29.3% and 27.9% in women and men, respectively. Proportions were higher in PL-PCC than negatives, for PEM in women OR=4.38 [95%CI:3.01-6.38]; in men OR = 4.78 [95%CI:3.13-7.29]; for OI in women 3.06 [95%CI:1.97-4.76]; in men 2.71 [95%CI:1.75-4.21]. Associated factors were age ≤ 60 years, ≥1 comorbidities, and living alone.

CONCLUSION: High proportions of PEM and OI are observed in PL-PCC. Standard screening for PEM and OI is recommended in PL-PCC to promote appropriate therapies.}, } @article {pmid38162867, year = {2023}, author = {Yagi, K and Asakura, T and Terai, H and Ohgino, K and Masaki, K and Namkoong, H and Chubachi, S and Miyata, J and Kawada, I and Kodama, N and Sakamoto, S and Umeda, A and Ishiguro, T and Ishii, M and Fukunaga, K}, title = {Clinical features of Japanese patients with gastrointestinal long-COVID symptoms.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {12}, pages = {998-1002}, pmid = {38162867}, issn = {2397-9070}, abstract = {Gastrointestinal (GI) long-COVID symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID. However, the clinical features of patients with GI long-COVID symptoms remain unclear. We conducted a large-scale prospective cohort study focusing on the clinical characteristics of patients with GI long-COVID symptoms in Japan. Among 943 COVID-19 patients, 58 patients (6.2%) had GI long-COVID symptoms. The health-related quality of life (QOL) parameters (the Short Form-8 [SF-8] and Euro Quality of Life 5 Dimensions 5 level [EQ-5D-5L]) at 12 months after diagnosis in patients with GI long-COVID symptoms were significantly lower than in those without GI long-COVID symptoms (P < 0.0001). Moreover, patients with GI long-COVID symptoms had more varied long-COVID symptoms compared to patients without GI long-COVID symptoms.}, } @article {pmid38159917, year = {2023}, author = {Tan, MS and Zulkifli, NA and Teng, W and Lim, PT}, title = {Clinical outcomes of children with COVID-19 infection in a low-risk centre in Malaysia.}, journal = {The Medical journal of Malaysia}, volume = {78}, number = {7}, pages = {853-856}, pmid = {38159917}, issn = {0300-5283}, mesh = {Child ; Humans ; Infant ; COVID-19/epidemiology ; Malaysia/epidemiology ; Pandemics ; *Post-Acute COVID-19 Syndrome/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; }, abstract = {INTRODUCTION: According to WHO, long-COVID or post- COVID-19 condition is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. A systematic review and meta-analyses published in 2022, which mainly focus on the Western population, revealed that the prevalence of long COVID was 25.24%. Literature regarding long-COVID in children in Asia was scarce. The objectives of our study were to assess the long-term effect of COVID-19 infection in children and its correlation to their acute COVID- 19 infection.

MATERIALS AND METHODS: This study was conducted in Hospital Kepala Batas (HKB), a district hospital in Penang State, Malaysia, which was the designated regional COVID hospital during the pandemic. It was a retrospective observational study, where children who were admitted from November 2020 to March 2021, and attended follow-up clinics from Jan 2021 to May 2021, were recruited.

RESULTS: This study comprised 90 subjects, from 3 months old to 12 years old, mean of 6.5 years old. When comparing asymptomatic and symptomatic children, children with comorbidities were more likely to be symptomatic with a pvalue of 0.045 using the Pearson Chi-square test. All our patients' symptoms resolved upon discharge. During followup at 2-4 months after COVID-19 infection, all children were reported as back to their usual selves. Fifteen patients had recurrent symptoms. Most of their symptoms pointed towards an acute infection. One patient had two episodes of illness, while the rest had one. The most common symptoms were cough, fever and runny nose. The average duration of illness of these 16 episodes was 4.5 days with a standard deviation of 2.48. None of these symptoms lasted more than seven days. None of them required hospital admission. None of them had recurrent COVID-19 infections. Tweleve out of 72 children who had been going to school stopped physical school after COVID-19 infection. Our findings differed from other studies. These could be due to the limitations that we faced.

CONCLUSION: Most children who contracted COVID-19 infection recovered fully after acute infection, and most of them recovered fully without long-term sequelae.}, } @article {pmid38159046, year = {2024}, author = {Lui, KO and Ma, Z and Dimmeler, S}, title = {SARS-CoV-2 induced vascular endothelial dysfunction: direct or indirect effects?.}, journal = {Cardiovascular research}, volume = {120}, number = {1}, pages = {34-43}, doi = {10.1093/cvr/cvad191}, pmid = {38159046}, issn = {1755-3245}, mesh = {Animals ; Humans ; SARS-CoV-2/metabolism ; *COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Endothelial Cells/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; *Vascular Diseases ; Mammals/metabolism ; }, abstract = {Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously express the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), yet accumulating evidence suggests that it is more predominantly expressed by pericytes and vascular smooth muscle cells of the mammalian blood vessel. Besides, replicative infection of ECs by SARS-CoV-2 has yet to be demonstrated both in vitro and in vivo. In this study, we review latest research on endothelial ACE2 expression in different vascular beds, and the heterogeneity in various EC subsets with differential ACE2 expression in response to SARS-CoV-2. We also discuss ACE2-independent alternative mechanisms underlying endothelial activation in COVID-19, and the clinical manifestations of SARS-CoV-2-induced endothelial dysfunction. Altogether, understanding ACE2-dependent and ACE2-independent mechanisms driving SARS-CoV-2-induced vascular dysfunction would shed light on strategies of more effective therapies targeting cardiovascular complications associated with COVID-19.}, } @article {pmid38158995, year = {2023}, author = {Kuznetsova, PI and Tanashyan, MM and Raskurazhev, AA and Zaslavskaya, KI}, title = {[The structure of post/long COVID fatigue syndrome. Prospects for correction].}, journal = {Terapevticheskii arkhiv}, volume = {95}, number = {5}, pages = {418-424}, doi = {10.26442/00403660.2023.05.202224}, pmid = {38158995}, issn = {0040-3660}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Dizziness ; Asthenia ; Prospective Studies ; *COVID-19/complications ; Fatigue/etiology ; }, abstract = {AIM: To study the features of post-COVID asthenic syndrome and evaluate the effectiveness of the drug containing the succinic acid complex with trimethylhydrazinium in its treatment.

MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the efficacy of sequential therapy with BRAINMAX[®] included 160 patients with a history of coronavirus infection within 12 to 16 weeks (not more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. Testing was performed on the following scores: VAS for headache score, MFI-20 asthenia score, PSQI test, FAS-10 fatigue score, DHI dizziness score, MoCA cognitive impairment score, Beck anxiety score, vegetative index of Kerdo.

RESULTS: PSQI questionnaire showed significant improvement in sleep quality in the study group: by -2.5 points [-4; -1] (p<0.001); there was a more pronounced significant decrease in the MFI-20 score of -19.5 points [-27; -11] (p<0.001); a significant decrease in the FAS-10 fatigue score by -9 [-13.5; -4] points (p<0.001); DHI dizziness score showed a decrease by -6 [-12; 0] points in the BRAINMAX[®] group (p=0.001); the score of Beck anxiety and depression scale decreased by -5 [-11; -2] points (p<0.001). Multiple linear regression data showed a significant increase of 0.56 (p=0.02) in the MoCA score.

CONCLUSION: Our study convincingly showed the effectiveness of therapy with BRAINMAX[®] in a wide range of symptoms in patients with the post-COVID syndrome.}, } @article {pmid38156388, year = {2023}, author = {Wang, F and Yin, Q and Zhu, L}, title = {Association between COVID-19 and sensorineural hearing loss: Evidence from a Mendelian randomization study in European and East Asian population.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {12}, pages = {e1108}, pmid = {38156388}, issn = {2050-4527}, support = {202105AC160044//Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province/ ; }, mesh = {Humans ; *COVID-19/epidemiology/genetics ; East Asian People ; Genome-Wide Association Study ; *Hearing Loss, Sensorineural/epidemiology/genetics ; Mendelian Randomization Analysis ; European People ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID), characterized by persistent and sometimes debilitating symptoms following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has garnered increasing attention as a potential public health crisis. Emerging evidence indicates a higher incidence of hearing loss in individuals who have had COVID 2019 (COVID-19) compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and sensorineural hearing loss remains unknown.

METHODS: To addresses this outstanding issue, we performed Mendelian randomization analysis to detect the causal association between COVID-19 and hearing loss using the largest genome-wide association study data to date in the European population and confirmed the results in the East Asian population. Comprehensively sensitive analyses were followed, including Cochran's Q test, Mendelian randomization (MR)-Egger intercept test, MR-pleiotropy residual sum and outlier, and leave-one-out analysis, to validate the robustness of our results.

RESULTS: Our results suggested that there is no causal association between COVID-19 and the risk of hearing loss in the European population. Neither the susceptibility, hospitalization, and severity of COVID-19 on hearing loss (inverse variance weighted method: odds ratio (OR) = 1.046, 95% confidence interval (CI) = 0.907-1.205, p = .537; OR = 0.995, 95% CI = 0.956-1.036, p = .823; OR = 0.995, 95% CI = 0.967-1.025, p = .76). Replicated analyses in the East Asian population yielded consistent results. No pleiotropy and heterogeneity were found in our results.

CONCLUSION: In conclusion, our MR results do not support a genetically predicted causal relationship between COVID-19 and sensorineural hearing loss. Thus, the associations observed in prior observational studies may have been influenced by confounding factors rather than a direct cause-and-effect relationship. More clinical and mechanism research are needed to further understand this association in the future.}, } @article {pmid38156079, year = {2023}, author = {Strubchevska, K and Rachkovska, A and Krenytska, D and Karbovskyy, V and Kozyk, M and Secor, B and Raksha, N and Vovk, T and Savchuk, O and Falalyeyeva, T and Kaminsky, R and Ostapchenko, L}, title = {Coagulation Parameters in Post-Covid-19 Condition in Relation to Various Titers of Anti-SARS-CoV-2 IgG in Blood Plasma.}, journal = {International journal of general medicine}, volume = {16}, number = {}, pages = {6127-6135}, pmid = {38156079}, issn = {1178-7074}, abstract = {BACKGROUND AND OBJECTIVES: Post-COVID-19 condition is thought to affect 10-20% of people at least 3 months after a diagnosis of COVID-19 and two months of symptoms. Post-COVID-19 condition presents itself with many clinical effects with varying degrees of severity ranging from a mild cough to a life-threatening coagulopathy. Our study aimed to identify a relationship between the titers of anti-SARS-CoV-2 IgG and anticoagulation parameters: antithrombin III (ATIII), protein C (PC) and thrombomodulin (TM).

MATERIALS AND METHODS: Blood plasma was collected from healthy donors aged 25-45 who had recovered from COVID-19 3-6 months ago and their titers of anti-SARS-CoV-2 IgG and ATIII, PC, and TM were measured.

RESULTS: We found that concentrations and activities of key anticoagulation parameters (ATIII, PC, and TM) measured in donor plasma during the post-COVID-19 varied in relation to the titers of anti-SARS-CoV-2 IgG.

CONCLUSION: While we identified a dysfunction of anticoagulation parameters in patients with post-COVID-19, we aim to explore the subpopulation antibody IgG fraction directly using in vivo and in vitro experiments with the possibility to contribute to the development of treatment options for post-COVID-19 conditions.}, } @article {pmid38156027, year = {2023}, author = {Kasi, LS and Moorthy, B}, title = {A Case Report on Care-Seeking Type Illness Anxiety Disorder after COVID-19 Infection.}, journal = {Case reports in psychiatry}, volume = {2023}, number = {}, pages = {3003499}, pmid = {38156027}, issn = {2090-682X}, abstract = {This case report highlights the diagnostic challenges presented by the overlapping symptoms of illness anxiety disorder (IAD) and long COVID-19 (LC-19). This case report focuses on a 58-year-old woman with care-seeking type IAD in the context of LC-19-associated symptoms. The patient experienced mild COVID-19 in August 2021. Since then, she has reported an increase in LC-19-associated symptoms, including cognitive deficits, breathlessness, fatigue, and anosmia. Despite largely normal laboratory results, imaging, and physical examinations, the patient's distress and care-seeking behaviors persisted, resulting in the diagnosis of IAD. Accurately differentiating between LC-19 and IAD is crucial for appropriate patient care. We discuss the importance of recognizing and treating IAD in patients with LC-19-associated symptoms and the need for further research on the correlation between IAD and both COVID-19 and LC-19.}, } @article {pmid38156008, year = {2023}, author = {He, KY and Lei, XY and Zhang, L and Wu, DH and Li, JQ and Lu, LY and Laila, UE and Cui, CY and Xu, ZX and Jian, YP}, title = {Development and management of gastrointestinal symptoms in long-term COVID-19.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278479}, pmid = {38156008}, issn = {1664-302X}, abstract = {BACKGROUND: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.

OBJECTIVE: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.

RESULTS: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.

CONCLUSION: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.}, } @article {pmid38155884, year = {2023}, author = {Shenoy, PU and Udupa, H and Ks, J and Babu, S and K, N and Jain, N and Das, R and Upadhyai, P}, title = {The impact of COVID-19 on pulmonary, neurological, and cardiac outcomes: evidence from a Mendelian randomization study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1303183}, pmid = {38155884}, issn = {2296-2565}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Fatigue Syndrome, Chronic ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Parkinson Disease ; SARS-CoV-2/genetics ; *Heart Failure ; Chest Pain ; Genetic Predisposition to Disease ; Headache ; }, abstract = {BACKGROUND: Long COVID is a clinical entity characterized by persistent health problems or development of new diseases, without an alternative diagnosis, following SARS-CoV-2 infection that affects a significant proportion of individuals globally. It can manifest with a wide range of symptoms due to dysfunction of multiple organ systems including but not limited to cardiovascular, hematologic, neurological, gastrointestinal, and renal organs, revealed by observational studies. However, a causal association between the genetic predisposition to COVID-19 and many post-infective abnormalities in long COVID remain unclear.

METHODS: Here we employed Mendelian randomization (MR), a robust genetic epidemiological approach, to investigate the potential causal associations between genetic predisposition to COVID-19 and long COVID symptoms, namely pulmonary (pneumonia and airway infections including bronchitis, emphysema, asthma, and rhinitis), neurological (headache, depression, and Parkinson's disease), cardiac (heart failure and chest pain) diseases, and chronic fatigue. Using two-sample MR, we leveraged genetic data from a large COVID-19 genome-wide association study and various disorder-specific datasets.

RESULTS: This analysis revealed that a genetic predisposition to COVID-19 was significantly causally linked to an increased risk of developing pneumonia, airway infections, headache, and heart failure. It also showed a strong positive correlation with chronic fatigue, a frequently observed symptom in long COVID patients. However, our findings on Parkinson's disease, depression, and chest pain were inconclusive.

CONCLUSION: Overall, these findings provide valuable insights into the genetic underpinnings of long COVID and its diverse range of symptoms. Understanding these causal associations may aid in better management and treatment of long COVID patients, thereby alleviating the substantial burden it poses on global health and socioeconomic systems.}, } @article {pmid38156240, year = {2023}, author = {Lyons, MD and Beekmann, SE and Polgreen, PM and Marschall, J}, title = {What do infectious disease specialists think about managing long COVID?.}, journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE}, volume = {3}, number = {1}, pages = {e236}, pmid = {38156240}, issn = {2732-494X}, support = {P30 DK054759/DK/NIDDK NIH HHS/United States ; }, abstract = {This survey of infectious disease providers on long COVID care revealed a lack of familiarity with existing resources, a sentiment of missing guidelines, and scarcity of dedicated care centers. The low response rate suggests that infectious disease specialists do not consider themselves as the primary providers of long COVID care.}, } @article {pmid38156116, year = {2023}, author = {Zisis, SN and Durieux, JC and Mouchati, C and Funderburg, N and Ailstock, K and Chong, M and Labbato, D and McComsey, GA}, title = {Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2.}, journal = {Pathogens & immunity}, volume = {8}, number = {2}, pages = {1-15}, pmid = {38156116}, issn = {2469-2964}, abstract = {OBJECTIVE: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC.

METHODS: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method.

RESULTS: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC.

CONCLUSION: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.}, } @article {pmid38154880, year = {2023}, author = {Massey, D and Sawano, M and Baker, AD and Güthe, DB and Güthe, N and Shidlovsky, SP and Fisher, L and Grady, CB and Caraballo, C and Zhou, T and Sharma, R and Krumholz, HM}, title = {Characterisation of internal tremors and vibration symptoms.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e077389}, pmid = {38154880}, issn = {2044-6055}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Tremor/etiology ; Vibration ; *COVID-19/complications ; Delivery of Health Care ; }, abstract = {OBJECTIVES: To describe the experiences of patients who have postacute sequelae SARS-CoV-2 infection with internal vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from individuals belonging to its Facebook group with a history of COVID-19 suffering from vibrations and tremors.

SETTING AND DESIGN: A narrative analysis was performed on 140 emails and 450 social media comments from 140 individuals collected as a response to a call to >180 000 individuals participating in Survivor Corps between 15 July and 27 July 2021. We used common coding techniques and the constant comparative method for qualitative data synthesis and categorising emails. Coded data were entered into NVivo V.12 to identify recurrent themes, theme connections and supporting quotations. Comments were analysed using Word Clouds, generated with R V.4.0.3 using quanteda, wordcloud and tm packages.

MAIN OUTCOME MEASURES: Patient-reported long COVID symptom themes and domains related to internal tremors and vibration.

RESULTS: The respondents' emails represented 22 themes and 7 domains pertaining to their experience with internal tremor and vibrations. These domains were as follows: (1) symptom experience, description and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment and (7) impact on individuals' lives and livelihood. There were 22 themes in total, each corresponding to one of the broader domains. Among the responses, many described symptoms that varied in location, timing and triggers, occurred soon after their COVID-19 infection, and were markedly debilitating. There were often frustrating experiences with the healthcare system.

CONCLUSIONS: This study describes key themes and experiences among a group of people reporting long COVID and having a prolonged and debilitating symptom complex that prominently features internal tremors and vibrations.}, } @article {pmid38153845, year = {2024}, author = {Wiederhold, BK}, title = {The Path Forward: Self-Management Strategies for Long COVID.}, journal = {Cyberpsychology, behavior and social networking}, volume = {27}, number = {2}, pages = {97-99}, doi = {10.1089/cyber.2023.29305.editorial}, pmid = {38153845}, issn = {2152-2723}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Self-Management ; }, } @article {pmid38152586, year = {2023}, author = {Almulla, AF and Al-Hakeim, HK}, title = {Editorial: Neuropsychiatric and neurodegenerative aspects of acute and long COVID.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1343930}, pmid = {38152586}, issn = {1662-5099}, } @article {pmid38151820, year = {2024}, author = {Khan, M and Majeed, S and Ain, Q and Nawaz, A and Sumra, KA and Lammi, V and Nihal, F and Afrah, A and Khan, EA and Khan, MI and Sadiq, F}, title = {Long COVID in Pakistan: a cross-sectional analysis of health and psychosocial outcomes.}, journal = {Psychology, health & medicine}, volume = {29}, number = {7}, pages = {1250-1264}, doi = {10.1080/13548506.2023.2297748}, pmid = {38151820}, issn = {1465-3966}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; Cross-Sectional Studies ; Female ; Male ; Pakistan/epidemiology ; Adult ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Young Adult ; Stress, Psychological/epidemiology ; Mental Health ; }, abstract = {According to the World Health Organization-led Delphi consensus, long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness that cannot be explained by alternate diagnosis. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed either face to face or via telephone, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychosocial impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). The symptoms of decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. The majority of the participants (83.3%) had moderate level of perceived stress, while moderate to severe levels of stress were observed in 17.3% of the individuals. Moreover, a high level of positive mental well-being was also observed. This study highlights the need for further research into the clinical aspects and implications of long COVID in Pakistan and emphasizes the importance of ongoing support for affected individuals.}, } @article {pmid38151544, year = {2024}, author = {Namayandeh, SM and Basti, M and Jambarsang, S and Ardekani, SMY}, title = {The impact of long COVID on health-related quality of life in patients 6 months after discharge with severe COVID-19.}, journal = {Immunogenetics}, volume = {76}, number = {1}, pages = {27-35}, pmid = {38151544}, issn = {1432-1211}, mesh = {Humans ; Male ; Female ; Middle Aged ; *Quality of Life/psychology ; Post-Acute COVID-19 Syndrome ; Patient Discharge ; *COVID-19 ; Cross-Sectional Studies ; }, abstract = {This study investigates the relationship between long COVID and health-related quality of life (HRQOL) in patients discharged for 6 months. It included 192 patients with a history of severe COVID-19 and 192 patients with a history of non-severe COVID-19 patients that were selected through quota sampling methods from the Medical Care Monitoring Center (MCMC) of hospitals in Shiraz, Iran, in 2020. Phone-based interviews were conducted to collect data using the short form of the 12-item health-related quality of life (SF-12) questionnaire. Descriptive statistics, including mean (standard deviation) and frequency (percentage), were utilized. Statistical tests, such as the chi-squared test, independent samples t-test, Fisher's exact test, and multiple linear regression models were performed. Statistical analysis was performed using SPSS software version 24, with a significance level of 0.05. Among 384 patients, 79.95% were married, with a mean age of 53.95 years. The majority of patients in both groups were male (57.81% in the severe group and 51.04% in the non-severe group). Patients with severe COVID-19 had significantly lower quality of life scores compared to those with non-severe COVID-19 (p < 0.001, 34.45 [SD = 6.59] versus 39.64 [SD = 5.07]). Furthermore, multiple linear regression analysis indicated that severe COVID-19 inducts a significant negative effect on HRQOL in patients after adjustment of confounders (p < 0.001, B = - 4.84). Patients with severe COVID-19 had lower HRQOL compared to those with a non-severe level. It is necessary to consider implementing policies aimed at providing social, psychological, or medical support to improve the HRQOL of patients with a history of severe COVID-19.}, } @article {pmid38150196, year = {2023}, author = {Bustos-Viviescas, BJ and Lozano Zapata, RE and García Yerena, CE}, title = {[Acid-base balance and long COVID: comments on metabolic-respiratory alterations].}, journal = {Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina)}, volume = {80}, number = {4}, pages = {568-573}, pmid = {38150196}, issn = {1853-0605}, mesh = {Humans ; *Acid-Base Equilibrium ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Kidney ; }, abstract = {Long COVID is a multi-organ pathology with important sequelae that affect the health and welfare of survivors from the cellular bioenergetics, in this case, the importance of considering the acid-base balance within the processes of evaluation and treatment of long COVID by health and sports professionals was addressed, given that different investigations have found important modifications in mitochondrial function that result in ventilation failures, causing alterations in the compensation-decompensation of respiratory and renal pH control (metabolic-respiratory acidosis and alkalosis).}, } @article {pmid38148981, year = {2023}, author = {Corrêa, BDC and Santos, EGR and Belgamo, A and Pinto, GHL and Xavier, SS and Silva, CC and Dias, ÁRN and Paranhos, ACM and Cabral, ADS and Callegari, B and Costa E Silva, AA and Quaresma, JAS and Falcão, LFM and Souza, GS}, title = {Smartphone-based evaluation of static balance and mobility in long-lasting COVID-19 patients.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1277408}, pmid = {38148981}, issn = {1664-2295}, abstract = {BACKGROUND: SARS-CoV-2 infection can lead to a variety of persistent sequelae, collectively known as long COVID-19. Deficits in postural balance have been reported in patients several months after COVID-19 infection. The purpose of this study was to evaluate the static balance and balance of individuals with long COVID-19 using inertial sensors in smartphones.

METHODS: A total of 73 participants were included in this study, of which 41 had long COVID-19 and 32 served as controls. All participants in the long COVID-19 group reported physical complaints for at least 7 months after SARS-CoV-2 infection. Participants were evaluated using a built-in inertial sensor of a smartphone attached to the low back, which recorded inertial signals during a static balance and mobility task (timed up and go test). The parameters of static balance and mobility obtained from both groups were compared.

RESULTS: The groups were matched for age and BMI. Of the 41 participants in the long COVID-19 group, 22 reported balance impairment and 33 had impaired balance in the Sharpened Romberg test. Static balance assessment revealed that the long COVID-19 group had greater postural instability with both eyes open and closed than the control group. In the TUG test, the long COVID-19 group showed greater acceleration during the sit-to-stand transition compared to the control group.

CONCLUSION: The smartphone was feasible to identify losses in the balance motor control and mobility of patients with long-lasting symptomatic COVID-19 even after several months or years. Attention to the balance impairment experienced by these patients could help prevent falls and improve their quality of life, and the use of the smartphone can expand this monitoring for a broader population.}, } @article {pmid38146337, year = {2023}, author = {Naeem, S and Oros, SM and Adams, CS and Rakesh, G}, title = {Treatment of Cognitive Deficits and Behavioral Symptoms Following COVID-19-Associated Autoimmune Encephalitis With Intravenous Immunoglobulin: A Case Report and Review of the Literature.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51071}, pmid = {38146337}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) is associated with long-term neuropsychiatric sequelae. We describe a 60-year-old male patient's history and symptom trajectory encompassing the development of behavioral symptoms and cognitive deficits following pneumonia and subsequent autoimmune encephalitis associated with COVID-19. We also describe changes in these facets with correlative changes in his immunological parameters after both acute intravenous immunoglobulin (IVIG) therapy and chronic periodic IVIG therapy every two weeks over the course of two years. We review the literature on the treatment of long COVID-19 symptoms spanning cognitive and behavioral domains. In addition, we also elucidate current literature on the role of IVIG infusions for these symptoms using our patient's presentation and improvement in symptoms as an illustrative example.}, } @article {pmid38146118, year = {2023}, author = {Paniskaki, K and Goretzki, S and Anft, M and Konik, MJ and Meister, TL and Pfaender, S and Lechtenberg, K and Vogl, M and Dogan, B and Dolff, S and Westhoff, TH and Rohn, H and Felderhoff-Mueser, U and Stervbo, U and Witzke, O and Dohna-Schwake, C and Babel, N}, title = {Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {34}, number = {12}, pages = {e14060}, doi = {10.1111/pai.14060}, pmid = {38146118}, issn = {1399-3038}, mesh = {Humans ; Child ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cytokines ; CD8-Positive T-Lymphocytes ; Quality of Life ; *COVID-19 ; Disease Progression ; Dyspnea ; }, abstract = {BACKGROUND: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce.

METHODS: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay.

RESULTS: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4[+] and CD8[+] T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8[+] T cells.

CONCLUSIONS: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.}, } @article {pmid38146040, year = {2024}, author = {Kwon, J and Milne, R and Rayner, C and Rocha Lawrence, R and Mullard, J and Mir, G and Delaney, B and Sivan, M and Petrou, S}, title = {Impact of Long COVID on productivity and informal caregiving.}, journal = {The European journal of health economics : HEPAC : health economics in prevention and care}, volume = {25}, number = {7}, pages = {1095-1115}, pmid = {38146040}, issn = {1618-7601}, support = {COV-LT2-0016//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; *Efficiency ; United Kingdom/epidemiology ; *Caregivers/economics/statistics & numerical data ; Adult ; Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; Cost of Illness ; }, abstract = {BACKGROUND: Around 2 million people in the UK suffer from Long COVID (LC). Of concern is the disease impact on productivity and informal care burden. This study aimed to quantify and value productivity losses and informal care receipt in a sample of LC patients in the UK.

METHODS: The target population comprised LC patients referred to LC specialist clinics. The questionnaires included a health economics questionnaire (HEQ) measuring productivity impacts, informal care receipt and service utilisation, EQ-5D-5L, C19-YRS LC condition-specific measure, and sociodemographic and COVID-19 history variables. Outcomes were changes from the incident infection resulting in LC to the month preceding the survey in paid work status/h, work income, work performance and informal care receipt. The human capital approach valued productivity losses; the proxy goods method valued caregiving hours. The values were extrapolated nationally using published prevalence data. Multilevel regressions, nested by region, estimated associations between the outcomes and patient characteristics.

RESULTS: 366 patients responded to HEQ (mean LC duration 449.9 days). 51.7% reduced paid work hours relative to the pre-infection period. Mean monthly work income declined by 24.5%. The average aggregate value of productivity loss since incident infection was £10,929 (95% bootstrap confidence interval £8,844-£13,014) and £5.7 billion (£3.8-£7.6 billion) extrapolated nationally. The corresponding values for informal caregiving were £8,726 (£6,247-£11,204) and £4.8 billion (£2.6-£7.0 billion). Multivariate analyses found significant associations between each outcome and health utility and C19-YRS subscale scores.

CONCLUSION: LC significantly impacts productivity losses and provision of informal care, exacerbated by high national prevalence of LC.}, } @article {pmid38145803, year = {2024}, author = {Johansson, AK and Omar, R and Lehmann, S and Sannevik, J and Mastrovito, B and Johansson, A}, title = {General and orofacial symptoms associated with acute and long COVID in 80- and 90-year-old Swedish COVID-19 survivors.}, journal = {Journal of dentistry}, volume = {141}, number = {}, pages = {104824}, doi = {10.1016/j.jdent.2023.104824}, pmid = {38145803}, issn = {1879-176X}, mesh = {Humans ; Aged ; Aged, 80 and over ; *Post-Acute COVID-19 Syndrome ; Sweden/epidemiology ; *COVID-19/epidemiology ; Oral Health ; *Scandinavians and Nordic People ; }, abstract = {OBJECTIVES: To describe acute and long COVID-19 symptoms among older elderly Swedes and to find predictive factors for the development symptoms associated with acute and long COVID.

MATERIAL AND METHODS: A questionnaire about general and oral health was mailed to all 80-year-olds (born 1942, n = 6299) and 90-year-olds (born 1932, n = 1904) in two Swedish counties. Participants reporting COVID-19 were asked to complete an additional questionnaire.

RESULTS: Overall response rate was 66 % (n = 5375). Affirmative responses to having been sick/tested positive for COVID-19 were reported by 577 persons. Response rate to the COVID-19 questionnaire was 49 %. The majority (88 %) reported some general symptoms during the acute stage while 44 % reported orofacial symptom/s. Reporting of any form of long-COVID general symptoms was 37 and 35 % for orofacial symptoms. Predictive factors for contracting COVID-19 (based on self-report from 2017) were living in elderly housing/senior care facility (OR 1.6, CI 1.0-2.3), large number (>10) of weekly social contacts (OR 1.5, CI 1.3-1.9), being married (OR 1.4, CI 1.1-1.7) and high school/university education (OR 1.3 CI 1.1-1-6). The highest odds ratio for general symptoms of long-COVID were a single complete denture (OR 5.0, CI 2.0-12.3), reporting bad breath (OR 3.7, CI 1.9-7.2) and daytime dry mouth (OR 2.2, CI 1.1-4.2). Regarding long-COVID orofacial symptoms, the highest risk factors were bad breath (OR 3.8, CI 1.9-7.5) and a single complete denture in one jaw (OR 3.4, CI 1.2-9.8).

CONCLUSION: Long-COVID general and orofacial symptoms are common among older elderly COVID-19 survivors CLINICAL SIGNIFICANCE: Oral microorganisms may be responsible for development of long-COVID symptoms. Health personnel managing COVID-19 patients should carefully examine dental status, especially in those having acrylic-based removable dentures, for oral signs and symptoms. If found, rigorous oral hygiene procedures should be carried out including cleaning/disinfection of the denture.}, } @article {pmid38145343, year = {2024}, author = {Abramoff, BA and Hentschel, C and Dillingham, IA and Dillingham, T and Baraniecki-Zwil, G and Williams, A and Pezzin, LE}, title = {The association of multiple sclerosis, traumatic brain injury, and spinal cord injury to acute and long COVID-19 outcomes.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {16}, number = {6}, pages = {553-562}, pmid = {38145343}, issn = {1934-1563}, support = {R01 HD108312/HD/NICHD NIH HHS/United States ; 5-R01-AG058718/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Retrospective Studies ; *Spinal Cord Injuries/epidemiology/complications ; Middle Aged ; *Multiple Sclerosis/epidemiology/complications ; *Brain Injuries, Traumatic/complications/epidemiology ; Adult ; SARS-CoV-2 ; Hospitalization/statistics & numerical data ; Length of Stay/statistics & numerical data ; Aged ; United States/epidemiology ; }, abstract = {BACKGROUND: Although persons with disabilities are a high-risk group, little is known about the association between specific disabling conditions and acute or long COVID outcomes.

OBJECTIVE: To examine the severity of acute SARS-CoV-2 infection and post-COVID outcomes among people with a preexisting diagnosis of multiple sclerosis (MS), spinal cord injury (SCI), or traumatic brain injury (TBI).

METHODS: This was a retrospective cohort study using the TrinetX Research Database, a large representative database of medical records. COVID-19-positive persons with MS, SCI, or TBI (cases) were matched 1:1 on age, gender, race, ethnicity, and comorbidities to COVID-19-positive persons without these diagnoses (controls). The main outcomes assessed were hospitalization for acute COVID-19, length of stay (LOS), the total number of hospitalizations, mortality, and incidence of six prevalent post-COVID sequelae within 6 months following a COVID-19 diagnosis.

RESULTS: There were 388,297 laboratory-confirmed COVID-19 cases identified. Of these cases, 2204 individuals had one of the following preexisting diagnoses: 51.3% TBI, 31.4% MS, and 17.3% SCI. People with TBI, MS, and SCI were significantly more likely to be hospitalized for COVID-19 (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.03-1.46) than matched controls. There was no difference in LOS, total hospitalizations, or mortality during the 6 months following the initial COVID diagnosis. Multivariable analyses reveal that persons with TBI, MS, and SCI were more likely to experience new weakness (OR = 1.54, 95% CI = 1.19-2.00), mobility difficulties (OR = 1.66, 95% CI = 1.17-2.35), and cognitive dysfunction (OR = 1.79, 95% CI = 1.38-2.33) than controls, even after controlling for the presence of these symptoms prior to their COVID infection and other risk factors. There were no differences in fatigue, pain, or dyspnea.

CONCLUSIONS: Having a history of MS, SCI or TBI was not associated with higher mortality risk from COVID-19. However, associations between these diagnoses and postacute COVID-19 symptoms raise concern about widening health outcome disparities for individuals with such potentially disabling conditions following COVID-19 infection.}, } @article {pmid38144461, year = {2023}, author = {Latifi, A and Flegr, J}, title = {Is recovery just the beginning? Persistent symptoms and health and performance deterioration in post-COVID-19, non-hospitalized university students-a cross-sectional study.}, journal = {Biology methods & protocols}, volume = {8}, number = {1}, pages = {bpad037}, pmid = {38144461}, issn = {2396-8923}, abstract = {Many individuals experience persistent symptoms such as deteriorated physical and mental health, increased fatigue, and reduced cognitive performance months after recovering from coronavirus disease 2019 (COVID-19). There is limited data on the long-term trajectory and prevalence of these symptoms, especially in milder cases. Our study aimed to assess the persistent effects of COVID-19 on physical and mental health, fatigue, and cognitive performance in a cohort of 214 students, averaging 21.8 years of age. Of these, 148 had contracted COVID-19 but were not hospitalized, with the time since infection ranging from 1 to 39 months. We utilized a comprehensive panel of cognitive tests to measure intelligence, memory, and psychomotor skills, and a detailed anamnestic questionnaire to evaluate physical and mental health. While contracting COVID-19 did not significantly impact overall health and performance, it was associated with increased reports of fatigue. However, the reported severity of the disease had a pronounced negative influence on physical health, mental well-being, fatigue, and reaction time. Trends of improvement in physical and mental health, as well as error rate, were observed within the first 2 years post-infection. However, fatigue and reaction time showed a trend of deterioration. Beyond the 2-year mark, physical health and error rate continued to improve, while mental health began to deteriorate. Fatigue and reaction time continued to decline. Overall, our findings suggest that some effects of contracting COVID-19 can persist or even deteriorate over time, even in younger individuals who had mild cases that did not require hospitalization.}, } @article {pmid38144169, year = {2023}, author = {Taenzer, M and Löffler-Ragg, J and Schroll, A and Monfort-Lanzas, P and Engl, S and Weiss, G and Brigo, N and Kurz, K}, title = {Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study.}, journal = {International journal of tryptophan research : IJTR}, volume = {16}, number = {}, pages = {11786469231220781}, pmid = {38144169}, issn = {1178-6469}, abstract = {BACKGROUND: Around 10% of people who had COVID-9 infection suffer from persistent symptoms such as fatigue, dyspnoea, chest pain, arthralgia/myalgia, sleep disturbances, cognitive dysfunction and impairment of mental health. Different underlying pathomechanisms appear to be involved, in particular inflammation, alterations in amino acid metabolism, autonomic dysfunction and gut dysbiosis.

AIM: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis.

PATIENTS AND METHODS: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (n = 25; 20 women, 5 men) in comparison to healthy controls (Ctrl, n = 8; 7 women, 1 man) and individuals with ME/CFS (n = 8; 2 women, 6 men). Concentrations of neurotransmitter precursors tryptophan, phenylalanine and their downstream metabolites, as well as their association with symptoms (fatigue, anxiety and depression) in the patients were examined.

RESULTS AND CONCLUSION: Phenylalanine levels were significantly lower in both the LC and ME/CFS patient groups when compared to the Ctrl group. In many LC patients, the concentrations of downstream metabolites of tryptophan and tyrosine, such as serotonin, dopamine and catecholamines, deviated from the reference ranges. Several symptoms (sleep disturbance, pain or autonomic dysfunction) were associated with certain metabolites. Patients experiencing fatigue had lower levels of kynurenine, phenylalanine and a reduced kynurenine to tryptophan ratio (Kyn/Trp). Lower concentrations of gamma-aminobutyric acid (GABA) and higher activity of kynurenine 3-monooxygenase (KMO) were observed in patients with anxiety. Conclusively, our results suggest that amino acid metabolism and neurotransmitter synthesis is disturbed in patients with LC and ME/CFS. The identified metabolites and their associated dysregulations could serve as potential biomarkers for elucidating underlying pathomechanisms thus enabling personalized treatment strategies for these patient populations.}, } @article {pmid38143784, year = {2023}, author = {Peterson, BM and Unger, I and Sun, S and Park, JY and Kim, J and Gunasekera, RS and Wilson, J and Galbadage, T}, title = {The vital role of exercise and nutrition in COVID-19 rehabilitation: synergizing strength.}, journal = {Frontiers in sports and active living}, volume = {5}, number = {}, pages = {1305175}, pmid = {38143784}, issn = {2624-9367}, abstract = {Since the outset of the COVID-19 pandemic, the global healthcare community has faced the challenge of understanding and addressing the ongoing and multi-faceted SARS-CoV-2 infection outcomes. As millions of individuals worldwide continue to navigate the complexities of post-hospitalization recovery, reinfection rates, and the increasing prevalence of Long-COVID symptoms, comprehensive COVID-19 rehabilitation strategies are greatly needed. Previous studies have highlighted the potential synergy between exercise and nutrition, suggesting that their integration into patient rehabilitation programs may yield improved clinical outcomes for survivors of COVID-19. Our group aimed to consolidate existing knowledge following the implementation of patient, intervention, comparison, and outcome (PICO) search strategies on the distinct and combined impacts of exercise and nutrition interventions in facilitating the recovery of COVID-19 patients following hospitalization, with a specific focus on their implications for both public health and clinical practice. The incorporation of targeted nutritional strategies alongside exercise-based programs may expedite patient recovery, ultimately promoting independence in performing activities of daily living (ADLs). Nonetheless, an imperative for expanded scientific inquiry remains, particularly in the realm of combined interventions. This mini-review underscores the compelling prospects offered by an amalgamated approach, advocating for the seamless integration of exercise and nutrition as integral components of post-hospitalization COVID-19 rehabilitation. The pursuit of a comprehensive understanding of the synergistic effects and effectiveness of exercise and nutrition stands as a crucial objective in advancing patient care and refining recovery strategies in the wake of this enduring global health crisis.}, } @article {pmid38143394, year = {2023}, author = {Braga, LW and Oliveira, SB and Moreira, AS and Martins Pereira, MEMDS and Serio, ASS and Carneiro, VDS and Freitas, LFP and Souza, LMDN}, title = {Long COVID neuropsychological follow-up: Is cognitive rehabilitation relevant?.}, journal = {NeuroRehabilitation}, volume = {53}, number = {4}, pages = {517-534}, doi = {10.3233/NRE-230212}, pmid = {38143394}, issn = {1878-6448}, mesh = {Humans ; Female ; Middle Aged ; Male ; Post-Acute COVID-19 Syndrome ; Cognitive Training ; Quality of Life ; *COVID-19/complications ; Neuropsychological Tests ; *Cognitive Dysfunction/etiology/psychology ; }, abstract = {BACKGROUND: Duration of neuropsychological disorders caused by long COVID, and the variables that impact outcomes, are still largely unknown.

OBJECTIVE: To describe the cognitive profile of patients with long COVID post-participation in a neuropsychological rehabilitation program and subsequent reassessment and identify the factors that influence recovery.

METHODS: 208 patients (mean age of 48.8 y.o.), mostly female, were reevaluated 25 months after their first COVID infection and 17 months after their initial evaluation. Patients underwent subjective assessment, Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing Tests (NEUPSILIN) for executive functions, Hospital Anxiety and Depression Scale (HADS) and WHOQol-Bref.

RESULTS: We noted a discrete improvement of neuropsychological symptoms 25 months after the acute stage of COVID-19; nonetheless, performance was not within the normative parameters of standardized neuropsychological testing. These results negatively impact QoL and corroborate patients' subjective assessments of cognitive issues experienced in daily life. Improvement was seen in those who participated in psychoeducational neuropsychological rehabilitation, had higher levels of education, and lower depression scores on the HADS.

CONCLUSION: Our data reveal the persistence of long-term cognitive and neuropsychiatric disorders in patients with long COVID. Neuropsychological rehabilitation is shown to be important, whether in-person or online.}, } @article {pmid38142603, year = {2024}, author = {Koonce, RM and Martin, BC}, title = {The association between suspected long-COVID and stimulant prescribing in the United States.}, journal = {Psychiatry research}, volume = {331}, number = {}, pages = {115686}, pmid = {38142603}, issn = {1872-7123}, support = {T32 DA022981/DA/NIDA NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; *Central Nervous System Stimulants/therapeutic use ; *Attention Deficit Disorder with Hyperactivity/drug therapy/epidemiology ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *COVID-19/epidemiology ; }, abstract = {OBJECTIVES: This study sought to determine the association between suspected long-COVID and receipt of a stimulant prescription among persons diagnosed with COVID-19 and to describe clinical and demographic factors associated with receiving a stimulant prescription.

METHODS: US patients 18 and older who had a COVID-19 diagnosis or a positive COVID-19 PCR test from April 1st, 2020 through December 21st, 2022 recorded in a national electronic health record data set obtained from TriNetX were assessed. Comparison subjects were propensity score matched on baseline covariates to those with a symptom of or diagnosis of long-COVID. A Cox Proportional Hazards models was used to estimate the influence of long-COVID on stimulant prescription receipt.

RESULTS: Those with long-COVID (n = 65,329) were twice as likely to be prescribed a stimulant as persons with only acute COVID-19 (n = 189,438, HR=2.162; 1.929-2.423). Among persons with long-COVID, persons with new onset ADHD (HR=7.196; 5.749- 9.007), opioid-related disorders (HR=2.140; 1.264-3.621) and mood disorders (HR=1.649; 1.336-2.035) were more likely to be prescribed a stimulant.

CONCLUSION: Further research describing the risks associated with increased stimulant use among persons with long-COVID is warranted.}, } @article {pmid38141960, year = {2024}, author = {Salmon, D and Slama, D and Linard, F and Dumesges, N and Le Baut, V and Hakim, F and Oustric, P and Seyrat, E and Thoreux, P and Marshall, E}, title = {Patients with Long COVID continue to experience significant symptoms at 12 months and factors associated with improvement: A prospective cohort study in France (PERSICOR).}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {140}, number = {}, pages = {9-16}, doi = {10.1016/j.ijid.2023.11.038}, pmid = {38141960}, issn = {1878-3511}, mesh = {Humans ; *Ageusia ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; France/epidemiology ; Antibodies, Viral ; }, abstract = {OBJECTIVES: This study examines long COVID symptoms course over 12 months, their impact on daily life, and associated factors for symptom relief.

METHODS: A prospective cohort study included 231 participants with long COVID at 12-month follow-up. Data on characteristics, symptom course, and remission were collected using a questionnaire and a remission scale. Poisson regression models were used to estimate the prevalence rate ratio (PRR) and 95% confidence intervals (CIs) for factors associated with symptom improvement.

RESULTS: Of the 231 participants, 63.2% developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12 months, only 8.7% (95% CI: 5.4-13.1%) reported complete remission, while 28.6% noted significant improvement. Most symptoms remained prevalent: asthenia (83.1%), neurocognitive/neurological (93.9%), cardiothoracic (77.9%), Musculoskeletal (78.8%). During long COVID, 62.2% stopped working, and only 32.5% resumed full-time professional activities. Presence of SARS-CoV-2 antibodies before vaccination increased the probability of improvement (aPRR: 1.60, P = 0.028), while ageusia at initial long COVID phase decreased the probability (aPRR: 0.38, P = 0.007).

CONCLUSIONS: Long-COVID symptoms persisted in the majority of participants after 12 months, with significant impacts on daily life and work. SARS-CoV-2 antibodies were associated with better prognosis, while persistent ageusia indicated a lower probability of improvement. These findings highlight the need for ongoing support and care for individuals with long COVID.}, } @article {pmid38141051, year = {2024}, author = {Tsai, J and Grace, A and Kurian, A}, title = {Incidence and psychiatric predictors of Long COVID beyond 3 months in a city-wide community sample in Texas.}, journal = {Journal of public health (Oxford, England)}, volume = {46}, number = {1}, pages = {e51-e59}, doi = {10.1093/pubmed/fdad276}, pmid = {38141051}, issn = {1741-3850}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Incidence ; Texas/epidemiology ; Longitudinal Studies ; }, abstract = {BACKGROUND: Studies have emerged about a syndrome of persistent symptoms of Coronavirus Disease-2019 (COVID-19) infection called 'Long COVID', which have mostly focused on the first 3 months. This study examined rates and predictors of Long COVID symptoms lasting beyond 3 months (termed Long2 COVID).

METHODS: A longitudinal cohort study using a population-based sample of 511 adults in San Antonio, Texas with laboratory-confirmed cases of COVID-19 were assessed for Long2 COVID. Inverse probability weighting was used.

RESULTS: In the sample, 19.18-59.10% met criteria for Long2 COVID depending on the definition. In general, Long COVID symptoms decreased after 3 months with the notable exception of an observed increase in loss of taste and smell. White Hispanic (adjusted odds ratio (aOR) = 7.66; 95% confidence interval (CI) = 1.78, 32.87) background and baseline depression symptoms (aOR = 1.30; 95% CI = 1.03, 1.65) were predictive of Long2 COVID. Long2 COVID was also associated with greater anxiety symptoms 6 months after onset of COVID-19.

CONCLUSIONS: A sizable proportion report COVID-19 symptoms lasting more than 3 months and some symptoms even increased over time. Adults who are Hispanic white adults or have depression may be at greater risk for Long2 COVID. Further research is needed on why some adults experience Long COVID and how to reduce the duration of illness.}, } @article {pmid38140991, year = {2024}, author = {Brigido, S and Manes, MT and Ingianni, N and Lanni, F and Cutolo, A and La Rovere, MT and Pavan, D and , }, title = {[Gender cardiology: focus on clinical and pathophysiological peculiarities in women with long COVID syndrome].}, journal = {Giornale italiano di cardiologia (2006)}, volume = {25}, number = {1}, pages = {6-13}, doi = {10.1714/4165.41585}, pmid = {38140991}, issn = {1972-6481}, mesh = {Female ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Cardiovascular System ; *Cardiology ; *Vascular Diseases ; }, abstract = {Long COVID is a clinical syndrome characterized by the persistence or development of symptoms due to COVID-19 at least 12 weeks after initial infection. More than 200 different symptoms have been ascribed to long COVID, the most common being fatigue, shortness of breath, and muscle weakness. Women have a three-fold higher risk of being diagnosed with long COVID, and the symptoms more often described are persistent weakness, chest pain, altered smell and taste, palpitations or muscle pain, as well as neurological, gastrointestinal and rheumatologic symptoms. Long COVID features are influenced by immune function, endothelial dysfunction and sex hormones. Moreover, it leads to systemic dysfunction, so various therapeutic strategies have been explored and still different trials are ongoing, mainly regarding anticoagulation and immuno-modulators. Nowadays the most quoted interventions are focused rehabilitation programs and pharmacological selected treatments in specifical cases. The aim of this review will be focusing the clinical and pathophysiological sex-related peculiarities to understand the different long COVID phenotypes and possibly address a better tailored approach and treatment.}, } @article {pmid38140174, year = {2023}, author = {Cegolon, L and Mauro, M and Sansone, D and Tassinari, A and Gobba, FM and Modenese, A and Casolari, L and Liviero, F and Pavanello, S and Scapellato, ML and Taus, F and Carta, A and Spiteri, G and Monaco, MGL and Porru, S and Larese Filon, F}, title = {A Multi-Center Study Investigating Long COVID-19 in Healthcare Workers from North-Eastern Italy: Prevalence, Risk Factors and the Impact of Pre-Existing Humoral Immunity-ORCHESTRA Project.}, journal = {Vaccines}, volume = {11}, number = {12}, pages = {}, pmid = {38140174}, issn = {2076-393X}, support = {101016167//European Union/ ; }, abstract = {Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.}, } @article {pmid38139400, year = {2023}, author = {Gostimirovic, M and Rajkovic, J and Bukarica, A and Simanovic, J and Gojkovic-Bukarica, L}, title = {Resveratrol and Gut Microbiota Synergy: Preventive and Therapeutic Effects.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139400}, issn = {1422-0067}, support = {NA//Ministry of Science, Technological Development and Innovations of Republic of Serbia/ ; }, mesh = {Humans ; Resveratrol/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/physiology ; *Noncommunicable Diseases ; Quality of Life ; Diet, High-Fat ; *COVID-19 ; }, abstract = {The role of an imbalanced high-fat diet in the pathophysiology of common chronic noncommunicable diseases has been known for years. More recently, the concept of 'gut microbiota' and the interaction between their composition and gut metabolites produced from the intake of dietary products have gained the focus of researchers, mostly from the perspective of the prevention of cardiovascular and metabolic disorders, which are still the leading cause of death globally. The aim of this work is to highlight the health benefits of the interaction between resveratrol (RSV), red grape polyphenol, and gut microbiota, through aspects of their therapeutic and preventive potentials. Since changed microbiota (mostly as a consequence of antibiotic overuse) contribute to the persistence of post ('long')-COVID-19 symptoms, these aspects will be covered too. Data were obtained from the electronic databases (MedLine/PubMed), according to specific keywords regarding the protective role of resveratrol, the gut microbiota, and their synergy. RSV exerts beneficial properties in the modulation of cardiovascular, metabolic, and post-COVID-19-related disorders. In healthy individuals, it maintains an ergogenic capacity, prevents oxidative stress, and modulates the inflammatory response. Overall, it improves quality of life. The RSV-gut-microbiota interaction is beneficial in terms of maintaining human health. Along with physical activity, it is key for the prevention of chronic noncommunicable diseases.}, } @article {pmid38139298, year = {2023}, author = {Garcia-Larragoiti, N and Cano-Mendez, A and Jimenez-Vega, Y and Trujillo, M and Guzman-Cancino, P and Ambriz-Murillo, Y and Viveros-Sandoval, ME}, title = {Inflammatory and Prothrombotic Biomarkers Contribute to the Persistence of Sequelae in Recovered COVID-19 Patients.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139298}, issn = {1422-0067}, support = {320085 CONAHCYT Frontier Science program//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; UMNSH-CIC 2022//Universidad Michoacana de San Nicolás de Hidalgo/ ; }, mesh = {Humans ; von Willebrand Factor/metabolism ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2/metabolism ; Biomarkers ; Disease Progression ; *Metabolic Syndrome ; }, abstract = {The presence of long COVID (LC) following SARS-CoV-2 infection is a common condition that affects the quality of life of patients and represents a diagnostic challenge due to the diversity of symptoms that may coexist. We still do not have accurate information regarding the pathophysiological pathways that generate the presence of LC, and so it is important to know the inflammatory and immunothrombotic biomarker profiles and their implications in order to characterize risk subgroups and establish early therapeutic strategies. We performed the determination of inflammatory and immunothrombotic biomarkers in volunteers with previous diagnoses of SARS-CoV-2. The inflammatory biomarkers were analyzed in plasma by flow cytometry, and we analyzed the von Willebrand factor (vWF) in the plasma samples using ELISA. The clinical variables and the presence or absence of long COVID symptoms were then analyzed. IL-6, sCD40L, p-Selectin, PSGL-1, PAI-1, tPA, D-Dimer, TF, and Factor IX levels were elevated in the groups with LC, especially in the subgroup of patients with metabolic syndrome (MetS). VWF levels were found to be increased in patients with sequelae and MetS. Our results confirmed the persistence of an active immunothrombotic state, and so it is important to identify the population at risk in order to provide adequate clinical follow-up.}, } @article {pmid38139027, year = {2023}, author = {Ailioaie, LM and Ailioaie, C and Litscher, G}, title = {Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {24}, pages = {}, pmid = {38139027}, issn = {1422-0067}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Gastrointestinal Microbiome ; Inflammation ; Dysbiosis ; }, abstract = {The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the "leaky gut" to the "leaky electron transport chain (ETC)" into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.}, } @article {pmid38138892, year = {2023}, author = {Alhammadin, G and Jarrar, Y and Madani, A and Lee, SJ}, title = {Exploring the Influence of VDR Genetic Variants TaqI, ApaI, and FokI on COVID-19 Severity and Long-COVID-19 Symptoms.}, journal = {Journal of personalized medicine}, volume = {13}, number = {12}, pages = {}, pmid = {38138892}, issn = {2075-4426}, support = {NRF-2020R1I1A3073778//the National Research Foundation of Korea/ ; }, abstract = {There is increasing evidence regarding the importance of vitamin D in the prognosis of coronavirus disease 2019 (COVID-19). Genetic variants in the vitamin D receptor (VDR) gene affect the response to vitamin D and have been linked to various diseases. This study investigated the associations of the major VDR genetic variants ApaI, FokI, and TaqI with the severity and long post-infection symptoms of COVID-19. In total, 100 Jordanian patients with confirmed COVID-19 were genotyped for the VDR ApaI, FokI, and TaqI variants using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. COVID-19 severity, the most commonly reported long-COVID-19 symptoms that lasted for >4 weeks from the onset of infection, and other variables were analyzed according to VDR genetic variants. In this study, ApaI and FokI polymorphisms showed no significant associations with COVID-19 severity (p > 0.05). However, a significant association was detected between the TaqI polymorphism and the severity of symptoms after infection with the SARS-CoV-2 virus (p = 0.04). The wild-type TaqI genotype was typically present in patients with mild illness, whereas the heterozygous TaqI genotype was present in asymptomatic patients. With regard to long-COVID-19 symptoms, the VDR heterozygous ApaI and wild-type TaqI genotypes were significantly associated with persistent fatigue and muscle pain after COVID-19 (p ˂ 0.05). Most carriers of the heterozygous ApaI genotype and carriers of the wild-type TaqI genotype reported experiencing fatigue and muscle pain that lasted for more than 1 month after the onset of COVID-19. Furthermore, the TaqI genotype was associated with persistent shortness of breath after COVID-19 (p = 0.003). Shortness of breath was more common among individuals with homozygous TaqI genotype than among individuals with the wild-type or heterozygous TaqI genotype. VDR TaqI is a possible genetic variant related to both COVID-19 severity and long-COVID-19 symptoms among Jordanian individuals. The associations between VDR TaqI polymorphisms and long-COVID-19 symptoms should be investigated in larger and more diverse ethnic populations.}, } @article {pmid38138524, year = {2023}, author = {Cai, L and Han, F and Ji, B and He, X and Wang, L and Niu, T and Zhai, J and Wang, J}, title = {In Silico Screening of Natural Flavonoids against 3-Chymotrypsin-like Protease of SARS-CoV-2 Using Machine Learning and Molecular Modeling.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {24}, pages = {}, pmid = {38138524}, issn = {1420-3049}, support = {R01 GM147673/GM/NIGMS NIH HHS/United States ; R01 GM149705/GM/NIGMS NIH HHS/United States ; R01GM147673/GM/NIGMS NIH HHS/United States ; R01GM149705/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2 ; Chymases ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Molecular Dynamics Simulation ; Flavonoids/pharmacology ; Machine Learning ; Protease Inhibitors/pharmacology ; Molecular Docking Simulation ; }, abstract = {The "Long-COVID syndrome" has posed significant challenges due to a lack of validated therapeutic options. We developed a novel multi-step virtual screening strategy to reliably identify inhibitors against 3-chymotrypsin-like protease of SARS-CoV-2 from abundant flavonoids, which represents a promising source of antiviral and immune-boosting nutrients. We identified 57 interacting residues as contributors to the protein-ligand binding pocket. Their energy interaction profiles constituted the input features for Machine Learning (ML) models. The consensus of 25 classifiers trained using various ML algorithms attained 93.9% accuracy and a 6.4% false-positive-rate. The consensus of 10 regression models for binding energy prediction also achieved a low root-mean-square error of 1.18 kcal/mol. We screened out 120 flavonoid hits first and retained 50 drug-like hits after predefined ADMET filtering to ensure bioavailability and safety profiles. Furthermore, molecular dynamics simulations prioritized nine bioactive flavonoids as promising anti-SARS-CoV-2 agents exhibiting both high structural stability (root-mean-square deviation < 5 Å for 218 ns) and low MM/PBSA binding free energy (<-6 kcal/mol). Among them, KB-2 (PubChem-CID, 14630497) and 9-O-Methylglyceofuran (PubChem-CID, 44257401) displayed excellent binding affinity and desirable pharmacokinetic capabilities. These compounds have great potential to serve as oral nutraceuticals with therapeutic and prophylactic properties as care strategies for patients with long-COVID syndrome.}, } @article {pmid38138278, year = {2023}, author = {Mileva, N and Vasilev, GH and Ganev, B and Chervenkov, L and Batselova, H and Tzotcheva, I and Tomov, L and Velikova, T and Lazova, S}, title = {Cardiovascular Manifestations of Multisystem Inflammatory Syndrome in Children: A Single-Center Bulgarian Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {12}, pages = {}, pmid = {38138278}, issn = {1648-9144}, support = {BG-RRP-2.004-0008//the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria/ ; }, mesh = {Bulgaria ; Male ; Retrospective Studies ; Systemic Inflammatory Response Syndrome ; Child ; Female ; Humans ; COVID-19/complications ; *Pericardial Effusion ; Post-Acute COVID-19 Syndrome ; *Pericarditis/complications/epidemiology ; *Heart Failure ; Interleukin-6 ; *Myocarditis/complications ; }, abstract = {Background and objectives: Multisystem inflammatory syndrome in children (MIS-C) poses challenges to the healthcare system, especially with frequent heart involvement. The current retrospective observational study aims to summarize the type and degree of cardiovascular involvement in children with MISC and to find possible associations between laboratory, inflammatory, and imaging abnormalities and the predominant clinical phenotype using a cluster analysis. Material and methods: We present a retrospective observational single-center study including 51 children meeting the MIS-C criteria. Results: Fifty-three percent of subjects presented with at least one sign of cardiovascular involvement (i.e., arterial hypotension, heart failure, pericardial effusion, myocardial dysfunction, pericarditis without effusion, myocarditis, coronaritis, palpitations, and ECG abnormalities). Acute pericarditis was found in 30/41 of the children (73%) assessed using imaging: 14/30 (46.7%) with small pericardial effusion and 16/30 (53.3%) without pericardial effusion. The levels of CRP were significantly elevated in the children with pericarditis (21.6 ± 13 mg/dL vs. 13.9 ± 11 mg/dL, p = 0.035), and the serum levels of IL-6 were higher in the children with small pericardial effusion compared to those without (191 ± 53 ng/L vs. 88 ± 27 ng/L, p = 0.041). Pericarditis with detectable pericardial effusion was significantly more frequent in the female vs. male subjects, 72% vs. 30% (p = 0.007). The hierarchical clustering analysis showed two clusters: Cluster 1 includes the children without cardiovascular symptoms, and Cluster 2 generalizes the MIS-C children with mild and severe cardiovascular involvement, combining pericarditis, myocarditis, heart failure, and low blood pressure. Also, subjects from Cluster 2 displayed significantly elevated levels of fibrinogen (5.7 ± 0.3 vs. 4.6 ± 0.3, p = 0.03) and IL-6 (158 ± 36 ng/mL vs. 66 ± 22 ng/mL, p = 0.032), inflammatory markers suggestive of a cytokine storm. Conclusions: Our results confirm that children with oligosymptomatic MIS-C or those suspected of long COVID-19 should be screened for possible cardiological involvement.}, } @article {pmid38138102, year = {2023}, author = {Fernández-de-Las-Peñas, C and Raveendran, AV and Giordano, R and Arendt-Nielsen, L}, title = {Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138102}, issn = {2076-2607}, abstract = {The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested.}, } @article {pmid38137757, year = {2023}, author = {Gryglewska-Wawrzak, K and Sakowicz, A and Banach, M and Bielecka-Dabrowa, A}, title = {Predictors of Long-COVID and Chronic Impairment of Exercise Tolerance in Spiroergometry in Patients after 15 Months of COVID-19 Recovery.}, journal = {Journal of clinical medicine}, volume = {12}, number = {24}, pages = {}, pmid = {38137757}, issn = {2077-0383}, support = {PMMHRI-BCO.75/2020//Polish Mother's Memorial Hospital Research Institute/ ; }, abstract = {BACKGROUND: The aim of the study was to identify factors that may cause the presence of long COVID and to assess factors that affect chronic limited exercise tolerance in spiroergometry after one-year follow-up in patients who had recovered from COVID-19.

METHODS: Of 146 patients hospitalised in the Cardiology Department, 82 completed a one-year follow-up (at least 15 months post-COVID-19 recovery). We compared their conditions at initial screening and follow-up to analyse the course of long COVID and exercise intolerance mechanisms. Clinical examinations, laboratory tests, echocardiography, cardiopulmonary exercise testing, and body composition analysis were performed.

RESULTS: The patients, after one-year follow-up, had significantly higher levels of high-sensitivity cardiac troponin T (hs-cTnT) (p = 0.03), left atrium diameter (LA) (p = 0.03), respiratory exchange ratio (RER) (p = 0.008), and total body water content percentage (TBW%) (p < 0.0001) compared to the 3-month assessment. They also had lower forced vital capacity in litres (FVC) (p = 0.02) and percentage (FVC%) (p = 0.001). The factors independently associated with a decline in maximum oxygen uptake (VO2max) after one-year follow-up included the percentage of fat (OR 2.16, 95% CI: 0.51-0.77; p = 0.03), end-diastolic volume (EDV) (OR 2.38, 95% CI 0.53-0.78; p = 0.02), and end-systolic volume (ESV) (OR 2.3, 95% CI: 0.52-0.78; p = 0.02).

CONCLUSIONS: Higher left ventricular volumes and fat content (%) were associated with a reduced peak VO2max when assessed 15 months after COVID-19 recovery.}, } @article {pmid38137533, year = {2023}, author = {Gyöngyösi, M and Hasimbegovic, E and Han, E and Zlabinger, K and Spannbauer, A and Riesenhuber, M and Hamzaraj, K and Bergler-Klein, J and Hengstenberg, C and Kammerlander, A and Kastl, S and Loewe, C and Beitzke, D}, title = {Improvement of Symptoms and Cardiac Magnetic Resonance Abnormalities in Patients with Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome (PASC-CVS) after Guideline-Oriented Therapy.}, journal = {Biomedicines}, volume = {11}, number = {12}, pages = {}, pmid = {38137533}, issn = {2227-9059}, support = {KLI 1064-B//FWF Austrian Science Fund/ ; 21176//Medical-Scientific Fund of the Mayor of Vienna City/ ; }, abstract = {Cardiac magnetic resonance (CMR) studies reported CMR abnormalities in patients with mild-moderate SARS-CoV-2 infection, suggesting ongoing myocardial inflammation. Patients (n = 278, 43 ± 13 years, 70.5% female) with post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) were included prospectively into the Vienna POSTCOV Registry between March 2021 and March 2023 (clinicaltrials.gov NCT05398952). Clinical, laboratory, and CMR findings were recorded. Patients with abnormal CMR results were classified into isolated chronic pericardial (with/without pleural) effusion, isolated cardiac function impairment, or both (myopericarditis) groups. Medical treatment included a nonsteroidal anti-inflammatory agent (NSAID) for pericardial effusion and a condition-adapted maximal dose of heart failure (HF) treatment. Three months after medical therapy, clinical assessment and CMR were repeated in 82 patients. Laboratory analyses revealed normal hematological, inflammatory, coagulation, and cardiac biomarkers. CMR abnormalities were found in 155 patients (55.8%). Condition-adapted HF treatment led to a significant increase in the left ventricular ejection fraction (LVEF) in patients with initially reduced LVEF (from 49 ± 5% to 56 ± 4%, p = 0.009, n = 25). Low-moderate doses of NSAIDs for 3 months significantly reduced pericardial effusion (from 4/3;5.75/mm to 2/0;3/mm, median/interquartile ranges/p < 0.001, n = 51). Clinical symptoms improved markedly with a decrease in CMR abnormalities, which might be attributed to the maintenance of NSAID and HF medical treatment for PASC-CVS.}, } @article {pmid38137118, year = {2023}, author = {Espinar-Herranz, K and Delgado-Lima, AH and Villatoro, BS and Garaboa, EM and Gómez, VS and Vides, LG and Bouhaben, J and Delgado-Losada, ML}, title = {Memory, Emotion, and Quality of Life in Patients with Long COVID-19.}, journal = {Brain sciences}, volume = {13}, number = {12}, pages = {}, pmid = {38137118}, issn = {2076-3425}, abstract = {(1) Background: Persistent COVID is characterized by the presence of fatigue, mental fog, and sleep problems, among others. We aimed to study cognitive abilities (attention, executive functions, memory, language) and psychological and emotional factors in a group of participants of the population with persistent COVID-19 and asymptomatic or non-COVID-19-infected patients; (2) Methods: A total of 86 participants aged 18 to 66 years (X = 46.76) took part in the study, with 57 individuals (66.27%) in the experimental group and 29 (33.73%) in the control group. A comprehensive assessment included neuropsychological evaluations, evaluations of anxious and depressive symptomatology, assessments of the impact of fatigue, sleep quality, memory failures in daily life, and the perceived general health status of the participants; (3) Results: significant differences between groups were found in incidental learning within the Key Numbers task (U = 462.5; p = 0.001; p = 0.022) and in the Direct Digit Span (U = 562; p = 0.022), but not in the Inverse Digit Span (U = 632.5; p = 0.105). Differences were also observed in the prospective memory task of the Rivermead Prospective Memory Tasks (from the Rivermead Behavioural Memory Test) in the recall of quotations (U = 610; p = 0.020) as well as in the recall of objects (U = 681.5; p = 0.032). Concerning the task of verbal fluency, significant differences were found for both phonological cues (p- and s-) (t = -2.190; p = 0.031) and semantic cues (animals) (t = -2.277; p = 0.025). In terms of the psychological impact assessment, significant differences were found in the emotional impact across all variables studied (fatigue, quality of sleep, memory lapses, and the perceived general health status), except for quality of life; (4) Conclusions: Our results suggest that the sequelae derived from persistent COVID may have an impact on people's lives, with higher levels of anxiety and depression, worse sleep quality, a greater number of subjective memory complaints, and a greater feeling of fatigue and impact on quality of life. Furthermore, poorer performance was observed in memory and verbal fluency.}, } @article {pmid38137114, year = {2023}, author = {Marinkovic, K and White, DR and Alderson Myers, A and Parker, KS and Arienzo, D and Mason, GF}, title = {Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome.}, journal = {Brain sciences}, volume = {13}, number = {12}, pages = {}, pmid = {38137114}, issn = {2076-3425}, support = {R21 AA027371/AA/NIAAA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; AA027371/NH/NIH HHS/United States ; }, abstract = {After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood. The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy ([1]H-MRS) was used to examine the neurochemical aspects of cell signaling with an emphasis on GABA levels in the occipital cortex. The PASC participants were compared to a control (CNT) group matched in demographics, intelligence, and an array of other variables. Controlling for tissue composition, biological sex, and alcohol intake, the PASC group had lower GABA+/water than CNT, which correlated with depression and poor sleep quality. The mediation analysis revealed that the impact of PASC on depression was partly mediated by lower GABA+/water, indicative of cortical hyperexcitability as an underlying mechanism. In addition, N-acetylaspartate (NAA) tended to be lower in the PASC group, possibly suggesting compromised neuronal integrity. Persistent neuroinflammation may contribute to the pathogenesis of PASC-related neurocognitive dysfunction.}, } @article {pmid38137059, year = {2023}, author = {Tavares-Júnior, JWL and Oliveira, DN and da Silva, JBS and Queiroz Feitosa, WL and Sousa, AVM and Marinho, SC and Cunha, LCV and Gaspar, SB and Gomes, CMP and de Oliveira, LLB and Moreira-Nunes, CA and Sobreira, EST and Moraes, MEA and Sobreira-Neto, MA and Montenegro, RC and Braga-Neto, P}, title = {Post-COVID-19 Cognitive Decline and Apoe Polymorphism: Towards a Possible Link?.}, journal = {Brain sciences}, volume = {13}, number = {12}, pages = {}, pmid = {38137059}, issn = {2076-3425}, support = {409123/2022-6//National Council for Scientific and Technological Development/ ; 88881.505364/2020-01a//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; //Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico/ ; }, abstract = {APOE ε4 polymorphism has been recently described as a possible association with cognitive deficits in COVID-19 patients. This research aimed to establish the correlation between COVID-19 and cognitive impairment, and the APOE gene polymorphism among outpatients. We performed a cross-sectional study with confirmed COVID-19 patients and neurological symptoms that persisted for more than three months from onset. APOE genotypes were determined. The final number of patients included in this study was 219, of which 186 blood samples were collected for APOE genotyping, evaluated 4.5 months after COVID-19. Among the participants, 143 patients (65.3%) reported memory impairment symptoms as their primary concern. However, this complaint was objectively verified through screening tests (Addenbrooke Cognitive Examination-Revised and Mini-Mental State Examination) in only 36 patients (16.4%). The group experiencing cognitive decline exhibited a higher prevalence of the APOE ε4 allele than the normal group (30.8% vs. 16.4%, respectively, p = 0.038). Furthermore, the APOE ε4 allele and anxiety symptoms remained significant after multivariate analysis. This study assessed an outpatient population where cognitive changes were the primary complaint, even in mild cases. Moreover, the ε4 allele, sleep disorders, and anxiety symptoms were more frequent in the cognitive decline group.}, } @article {pmid38136038, year = {2023}, author = {Schmidt, M and Hébert, S and Wallukat, G and Ponader, R and Krickau, T and Galiano, M and Reutter, H and Woelfle, J and Agaimy, A and Mardin, C and Hoerning, A and Hohberger, B}, title = {"Multisystem Inflammatory Syndrome in Children"-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {38136038}, issn = {2227-9067}, abstract = {BACKGROUND: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer-BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year.

CONCLUSIONS: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.}, } @article {pmid38135813, year = {2024}, author = {Ashktorab, H and Challa, SR and Singh, G and Nanduri, S and Ibrahim, M and Martirosyan, Z and Whitsell, P and Chirumamilla, LG and Shayegh, N and Watson, K and Smith, T and Ogwo, V and Kolawole, O and Littleton, M and Morrison, N and Nair, V and Byer, D and Dawodu, DO and Lexima, P and Rashid, M and Deverapalli, M and Atluri, SM and Nezamloo, A and Nasrin, F and Kim, RJ and Sherif, Z and Oskrochi, G and Carethers, JM and Brim, H}, title = {Gastrointestinal Manifestations and Their Association with Neurologic and Sleep Problems in Long COVID-19 Minority Patients: A Prospective Follow-Up Study.}, journal = {Digestive diseases and sciences}, volume = {69}, number = {2}, pages = {562-569}, pmid = {38135813}, issn = {1573-2568}, support = {R01 CA258519/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; *COVID-19/complications/diagnosis/epidemiology ; SARS-CoV-2 ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; COVID-19 Vaccines ; *Gastrointestinal Diseases/diagnosis/epidemiology/etiology ; *Liver Diseases/complications ; Vomiting ; *Sleep Wake Disorders/etiology/complications ; }, abstract = {BACKGROUND: Long-COVID is a condition post SARS-CoV-2 infection with persistent or recurring symptoms affecting multiple organs, and may involve viral persistence, changes to the microbiome, coagulopathies, and alterations to neuro-immune interactions. These factors can disrupt the Gut-Brain Axis, which is a complex system involving bidirectional communication between the central nervous system and the gastrointestinal (GI) system. As a result of these disruptions, individuals with long-COVID may develop post-infectious functional GI disorders, which can cause a range of symptoms affecting the digestive system.

AIM: To understand frequency of GI manifestations of Long-COVID and to determine association with sleep or neurological symptoms in a predominantly minority population.

METHODS: We included patients with positive SARS-CoV-2 PCR (n = 747) who were hospitalized from Feb. 2020 to May 2021 at Howard University Hospital and followed between 6 and 12 months from discharge. GI, sleep, and neurological symptoms (via the Montreal Cognitive Assessment (MoCA) scoring system) were assessed using a standardized questionnaire. Linear regression analysis, χ[2] and Fisher's exact test were utilized to determine the statistical significance of correlations of GI/Neuro/COVID.

RESULTS: The mean age of patients was 58, with 51.6% females and a predominant African American ethnicity (73.6%, n = 550). A total of 108 patients died during their initial hospital stay, with the remaining 639 patients followed-up. Three hundred fifty (350) patients responded to the questionnaire (57 patients died during the follow-up period). Overall, 39 (13.3%) patients reported GI-related symptoms, out of which 19 (6.4%) had persistent symptoms and 20 (6.8%) developed new onset GI symptoms. Nausea and vomiting were the most common 24/39 (61.5%), followed by abdominal pain 7/39 (18%), diarrhea 5/39 (12.8%), and others 3/39 (7.6%). Patients who presented with vomiting during acute SARS-CoV-2 infection were more likely to have Long-COVID GI manifestations (P = 0.023). Use of ACE inhibitors, abnormal lymphocyte count and elevated ferritin are other variables that showed significant associations with Long-COVID GI manifestations (P = 0.03, 0.006 and 0.03, respectively). During follow-up, a total of 28 (9.5%) patients reported difficulty with sleep and 79 (27%) patients had abnormal MoCA assessment. With further analysis, there was a trend between presentation of GI symptoms on admission with abnormal MoCA assessment, and an association between abnormal LFTs and history of liver disease during hospitalization with subsequent sleep problems. Baseline characteristics, clinical comorbidities, other laboratory values, hospital length of stay, mechanical ventilation, medications during hospitalization, re-admission and Flu or COVID-19 vaccination have not shown any association with Long-COVID GI symptoms in our cohort.

CONCLUSION: Dyspeptic symptoms were common GI manifestations in the acute and post COVID periods. GI symptoms, abnormal LFTs and a history of liver disease during the acute infectious phase associates with abnormal MoCA and sleep problems during follow-up. Further large population studies are needed to determine if COVID-19 leads to a GI symptoms-associated Long-COVID phenotypes and other symptoms through the Gut-Brain-Axis.}, } @article {pmid38132646, year = {2023}, author = {Zimmermann, P and Sourij, H and Aberer, F and Rilstone, S and Schierbauer, J and Moser, O}, title = {SGLT2 Inhibitors in Long COVID Syndrome: Is There a Potential Role?.}, journal = {Journal of cardiovascular development and disease}, volume = {10}, number = {12}, pages = {}, pmid = {38132646}, issn = {2308-3425}, abstract = {The coronavirus disease (COVID)-19 has turned into a pandemic causing a global public health crisis. While acute COVID-19 mainly affects the respiratory system and can cause acute respiratory distress syndrome, an association with persistent inflammatory stress affecting different organ systems has been elucidated in long COVID syndrome (LCS). Increased severity and mortality rates have been reported due to cardiophysiological and metabolic systemic disorders as well as multiorgan failure in COVID-19, additionally accompanied by chronic dyspnea and fatigue in LCS. Hence, novel therapies have been tested to improve the outcomes of LCS of which one potential candidate might be sodium-glucose cotransporter 2 (SGLT2) inhibitors. The aim of this narrative review was to discuss rationales for investigating SGLT2 inhibitor therapy in people suffering from LCS. In this regard, we discuss their potential positive effects-next to the well described "cardio-renal-metabolic" conditions-with a focus on potential anti-inflammatory and beneficial systemic effects in LCS. However, potential beneficial as well as potential disadvantageous effects of SGLT2 inhibitors on the prevalence and long-term outcomes of COVID-19 will need to be established in ongoing research.}, } @article {pmid38131885, year = {2023}, author = {Sideratou, CM and Papaneophytou, C}, title = {Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems.}, journal = {Infectious disease reports}, volume = {15}, number = {6}, pages = {806-830}, pmid = {38131885}, issn = {2036-7430}, abstract = {The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as 'long- COVID-19' (or simply 'long- COVID'), emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review summarizes the primary effects of long COVID on the respiratory, cardiovascular, and nervous systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.}, } @article {pmid38131727, year = {2023}, author = {Horlick, S and Krysa, JA and Brehon, K and Pohar Manhas, K and Kovacs Burns, K and Russell, K and Papathanassoglou, E and Gross, DP and Ho, C}, title = {Exploring Rehabilitation Provider Experiences of Providing Health Services for People Living with Long COVID in Alberta.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {24}, pages = {}, pmid = {38131727}, issn = {1660-4601}, support = {Emerging COVID-19 Research Gaps and Priorities/CAPMC/CIHR/Canada ; }, mesh = {Humans ; Alberta/epidemiology ; *Post-Acute COVID-19 Syndrome ; Qualitative Research ; *COVID-19/epidemiology ; Health Services ; }, abstract = {BACKGROUND: COVID-19 infection can result in persistent symptoms, known as long COVID. Understanding the provider experience of service provision for people with long COVID symptoms is crucial for improving care quality and addressing potential challenges. Currently, there is limited knowledge about the provider experience of long COVID service delivery.

AIM: To explore the provider experience of delivering health services to people living with long COVID at select primary, rehabilitation, and specialty care sites.

DESIGN AND SETTING: This study employed qualitative description methodology. Semi-structured interviews were conducted with frontline providers at primary care, rehabilitation, and specialty care sites across Alberta. Participants were interviewed between June and September 2022.

METHOD: Interviews were conducted virtually over zoom, audio-recorded, and transcribed with consent. Iterative inductive qualitative content analysis of transcripts was employed. Relationships between emergent themes were examined for causality or reciprocity, then clustered into content areas and further abstracted into a priori categories through their interpretive joint meaning.

PARTICIPANTS: A total of 15 participants across Alberta representing diverse health care disciplines were interviewed.

RESULTS: Main themes include: the importance of education for long COVID recognition; the role of symptom acknowledgement in patient-centred long COVID service delivery; the need to develop recovery expectations; and opportunities for improvement of navigation and wayfinding to long COVID services.

CONCLUSIONS: Provider experience of delivering long COVID care can be used to inform patient-centred service delivery for persons with long COVID symptoms.}, } @article {pmid38131056, year = {2023}, author = {Baldwin, K and Wanson, A and Gilecki, LA and Dalton, C and Peters, E and Halpape, K}, title = {Intranasal ketamine as a treatment for psychiatric complications of long COVID: A case report.}, journal = {The mental health clinician}, volume = {13}, number = {5}, pages = {239-243}, pmid = {38131056}, issn = {2168-9709}, abstract = {BACKGROUND: Neuropsychiatric symptoms associated with long COVID are a growing concern. A proposed pathophysiology is increased inflammatory mediators. There is evidence that typical serotonergic antidepressants have limited efficacy in the presence of inflammation. Although ketamine has shown promise in MDD, there is limited evidence supporting the use of ketamine to treat depressive symptoms associated with long COVID.

CASE REPORT: This case took place on an inpatient psychiatry unit in a Canadian hospital. The patient was admitted with a 10-month history of worsening depression and suicidality following infection with COVID-19. Depressive symptoms and suicidal ideation were assessed throughout treatment using the Montgomery-Asberg Depression Rating Scale (MADRS). Written informed consent was obtained prior to data collection. This patient received 4 doses of intranasal ketamine which resulted in rapid improvement of depressive symptoms and complete resolution of suicidality with no major adverse events.

DISCUSSION: There is evidence to support long COVID symptoms result from dysregulated inflammatory processes. The presence of inflammation in patients with MDD has correlated to poor outcomes with first-line antidepressants. It has been demonstrated that IV ketamine is associated with decreased inflammatory mediators and proportional decrease in depressive symptoms.

CONCLUSIONS: Intranasal ketamine in this case was effective at treating depressive symptoms and suicidal ideation associated with long COVID. This is consistent with available data that demonstrates ketamine's efficacy in reducing inflammatory mediators associated with neuropsychiatric symptoms. Therefore, ketamine may be a potential therapeutic option to treat long COVID and persistent depressive symptoms.}, } @article {pmid38130596, year = {2023}, author = {Richard, SA and Scher, AI and Rusiecki, J and Byrne, C and Berjohn, CM and Fries, AC and Lalani, T and Smith, AG and Mody, RM and Ganesan, A and Huprikar, N and Colombo, RE and Colombo, CJ and Schofield, C and Lindholm, DA and Mende, K and Morris, MJ and Jones, MU and Flanagan, R and Larson, DT and Ewers, EC and Bazan, SE and Saunders, D and Maves, RC and Livezey, J and Maldonado, CJ and Edwards, MS and Rozman, JS and O'Connell, RJ and Simons, MP and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and , }, title = {Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.}, journal = {Open forum infectious diseases}, volume = {10}, number = {12}, pages = {ofad579}, pmid = {38130596}, issn = {2328-8957}, support = {Y01 AI005072/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain.

METHODS: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health.

RESULTS: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70).

CONCLUSIONS: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.}, } @article {pmid38130252, year = {2023}, author = {Pendolino, AL and Ottaviano, G and Navaratnam, AV and Scarpa, B and Andrews, PJ}, title = {Clinical factors influencing olfactory performance in patients with persistent COVID-19 smell loss longer than 1 year.}, journal = {Laryngoscope investigative otolaryngology}, volume = {8}, number = {6}, pages = {1449-1458}, pmid = {38130252}, issn = {2378-8038}, abstract = {OBJECTIVES: Factors affecting persistence of COVID-19-related olfactory dysfunction (OD) remain partially unknown. We aim to evaluate the clinical factors which could influence olfactory performance in patients with persistent COVID-19-related smell loss.

METHODS: A retrospective analysis of 100 patients with persistent COVID-19-related OD was performed between October 2020 and December 2022 at a single-center long-COVID smell clinic. All subjects underwent smell assessment using Sniffin' Sticks (S'S) extended test, nasal endoscopy, nasal airflow evaluation (peak nasal inspiratory flow [PNIF]), allergy test (skin prick test [SPT]) for common aeroallergens, MRI of the head and patient-reported outcome measures (PROMs-VAS, SF-36, Short QOD-NS, SNOT-22). Based on S'S score, subjects were divided into normosmics (TDI ≥ 30.75) and dysosmics (TDI < 30.75).

RESULTS: The median age was 42 years and the median length of patient-reported OD was 1.4 years. 20 patients (20.0%) were normosmic at the time of S'S assessment. Dysosmic patients were found to have significantly lower scores at the SF-36 health domains for energy/fatigue (p = .0004) and emotional wellbeing (p = .04) when compared to normosmics. A moderate correlation (r = .45-.59) between S'S scores and some PROMs was also demonstrated. At the multivariate analysis higher PNIF scores positively influenced odor threshold (p = .001) while positivity to SPT negatively influenced odor identification (p = .04).

CONCLUSIONS: Impairment of nasal airflow and sensitivity to aeroallergens can negatively affect olfactory performance in COVID-19-related OD. Long-COVID smell loss deeply affects QoL although recovery of olfaction can bring it back to a normal range.

LEVEL OF EVIDENCE: IV.}, } @article {pmid38130117, year = {2024}, author = {Holland, AE and Fineberg, D and Marceau, T and Chong, M and Beaman, J and Wilson, L and Buchanan, JA and Uren, J and Dal Corso, S and Lannin, NA and Hoffman, M and Mellerick, CR and Fernando, K and Bondarenko, J}, title = {The Alfred Health post-COVID-19 service, Melbourne, 2020-2022: an observational cohort study.}, journal = {The Medical journal of Australia}, volume = {220}, number = {2}, pages = {91-96}, doi = {10.5694/mja2.52192}, pmid = {38130117}, issn = {1326-5377}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Fatigue ; Dyspnea ; }, abstract = {OBJECTIVES: To determine the uptake of the Alfred Health Post-COVID service among people hospitalised with coronavirus disease 2019 (COVID-19) or referred by general practitioners; to describe their characteristics and symptoms at eight weeks and the clinical services they required.

STUDY DESIGN: Observational cohort study.

SETTING: Outpatient post-COVID-19 follow-up service in a tertiary Melbourne hospital.

PARTICIPANTS: All people admitted to Alfred Health (inpatients, hospital-in-the-home) with COVID-19, 19 March 2020 - 28 December 2022; people with persistent symptoms referred by general practitioners in the Alfred Health catchment area during 2022.

INTERVENTION: Questionnaire-based symptom assessment eight weeks after onset of COVID-19. Dyspnoea, fatigue, depression, anxiety, and post-traumatic stress disorder were assessed with standardised tools, as were health status and health-related quality of life; return to work or study, weight loss, and altered cognition and memory were also assessed. Screening was followed by physical assessment and management at the service (specialist general medicine review, physiotherapist, allied health assistant, neuropsychologist) and referral to other specialist medical services as required.

MAIN OUTCOME MEASURES: Proportion of eligible people who used the service for follow-up at eight weeks; proportions of service users who reported symptoms and return to pre-COVID-19 employment or study; clinical services required by service users.

RESULTS: Of 6712 people invited for screening, 726 completed questionnaires (11%). At least one persistent symptom was reported by 385 of 642 respondents (60% of respondents, 5.7% of invitees), most frequently memory (371 of 656, 57%) or concentration problems (431 of 656, 66%), dyspnoea (197 of 703, 28%), and extreme fatigue (189 of 673, 28%). Sixty-seven of 453 respondents had not returned to pre-COVID-19 work or study (15%). People were referred to a variety of medical and non-medical services for management, including specialist medical clinics, allied health, and rehabilitation. Among 71 people who also completed questionnaires at twelve months, the proportions who reported fatigue, anxiety, and memory and concentration changes were similar at both assessments.

CONCLUSIONS: After acute COVID-19 that required hospital admission or was followed by persistent symptoms in community care, a small proportion of people (5.7%) reported symptoms that required medical and allied health specialist assessment and management. Our findings may assist planning services for people with long COVID.}, } @article {pmid38128935, year = {2023}, author = {Fyffe, I and Sorensen, J and Carroll, S and MacPhee, M and Andrews-Paul, A and Crooks, VA and Freeman, S and Davison, K and Walls, J and Berndt, A and Shams, B and Sivan, M and Mithani, A}, title = {Long COVID in long-term care: a rapid realist review.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e076186}, pmid = {38128935}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/therapy ; Delivery of Health Care ; Long-Term Care ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {OBJECTIVES: The goals of this rapid realist review were to ask: (a) what are the key mechanisms that drive successful interventions for long COVID in long-term care (LTC) and (b) what are the critical contexts that determine whether the mechanisms produce the intended outcomes?

DESIGN: Rapid realist review.

DATA SOURCES: Medline, CINAHL, Embase, PsycINFO and Web of Science for peer-reviewed literature and Google for grey literature were searched up to 23 February 2023.

ELIGIBILITY CRITERIA: We included sources focused on interventions, persons in LTC, long COVID or post-acute phase at least 4 weeks following initial COVID-19 infection and ones that had a connection with source materials.

DATA EXTRACTION AND SYNTHESIS: Three independent reviewers searched, screened and coded studies. Two independent moderators resolved conflicts. A data extraction tool organised relevant data into context-mechanism-outcome configurations using realist methodology. Twenty-one sources provided 51 intervention data excerpts used to develop our programme theory. Synthesised findings were presented to a reference group and expert panel for confirmatory purposes.

RESULTS: Fifteen peer-reviewed articles and six grey literature sources were eligible for inclusion. Eleven context-mechanism-outcome configurations identify those contextual factors and underlying mechanisms associated with desired outcomes, such as clinical care processes and policies that ensure timely access to requisite resources for quality care delivery, and resident-centred assessments and care planning to address resident preferences and needs. The underlying mechanisms associated with enhanced outcomes for LTC long COVID survivors were: awareness, accountability, vigilance and empathetic listening.

CONCLUSIONS: Although the LTC sector struggles with organisational capacity issues, they should be aware that comprehensively assessing and monitoring COVID-19 survivors and providing timely interventions to those with long COVID is imperative. This is due to the greater care needs of residents with long COVID, and coordinated efficient care is required to optimise their quality of life.}, } @article {pmid38128008, year = {2023}, author = {Metz, TD and Clifton, RG and Gallagher, R and Gross, RS and Horwitz, LI and Jacoby, VL and Martin-Herz, SP and Peralta-Carcelen, M and Reeder, HT and Beamon, CJ and Chan, J and Chang, AA and Costantine, MM and Fitzgerald, ML and Foulkes, AS and Gibson, KS and Güthe, N and Habli, M and Hackney, DN and Hoffman, MK and Hoffman, MC and Hughes, BL and Katz, SD and Laleau, V and Mallett, G and Mendez-Figueroa, H and Monzon, V and Palatnik, A and Palomares, KTS and Parry, S and Pettker, CM and Plunkett, BA and Poppas, A and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Schlater, SM and Sciurba, FC and Simhan, HN and Skupski, DW and Sowles, A and Thaweethai, T and Thomas, GL and Thorp, JM and Tita, AT and Weiner, SJ and Weigand, S and Yee, LM and Flaherman, VJ and , }, title = {Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0285351}, pmid = {38128008}, issn = {1932-6203}, support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Pregnancy ; *COVID-19/epidemiology ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.

DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.

Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.}, } @article {pmid38126937, year = {2024}, author = {Razzaq, A and Disoma, C and Zhou, Y and Tao, S and Chen, Z and Liu, S and Zheng, R and Zhang, Y and Liao, Y and Chen, X and Liu, S and Dong, Z and Xu, L and Deng, X and Li, S and Xia, Z}, title = {Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID-19.}, journal = {Reviews in medical virology}, volume = {34}, number = {1}, pages = {e2500}, doi = {10.1002/rmv.2500}, pmid = {38126937}, issn = {1099-1654}, mesh = {Humans ; Antiviral Agents/therapeutic use/pharmacology ; *COVID-19 ; COVID-19 Drug Treatment ; *ErbB Receptors/genetics/metabolism ; Erlotinib Hydrochloride/therapeutic use ; Post-Acute COVID-19 Syndrome ; Pulmonary Fibrosis/metabolism ; SARS-CoV-2/metabolism ; *Signal Transduction/drug effects ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.}, } @article {pmid38126489, year = {2023}, author = {Mill, JG and Polese, J}, title = {Post-COVID Syndrome or Long COVID: A New Challenge for the Healthcare System.}, journal = {Arquivos brasileiros de cardiologia}, volume = {120}, number = {11}, pages = {e20230750}, pmid = {38126489}, issn = {1678-4170}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Delivery of Health Care ; }, } @article {pmid38124476, year = {2024}, author = {Shetty, AJ and Banerjee, M and Prasad, TN and Bhadada, SK and Pal, R}, title = {Do vitamin D levels or supplementation play A role in COVID-19 outcomes?-a narrative review.}, journal = {Annals of palliative medicine}, volume = {13}, number = {1}, pages = {162-177}, doi = {10.21037/apm-23-113}, pmid = {38124476}, issn = {2224-5839}, mesh = {Humans ; *COVID-19 ; Dietary Supplements ; SARS-CoV-2 ; Vitamin D/therapeutic use ; *Vitamin D Deficiency/complications ; }, abstract = {BACKGROUND AND OBJECTIVE: Hypovitaminosis D has been proposed as a risk factor for increased susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and severe outcomes in coronavirus disease 2019 (COVID-19). Likewise, vitamin D supplementation has been proposed as an effective means for preventing and improving clinical outcomes in COVID-19. Nevertheless, available data are markedly inconsistent and contradictory. Considering the heterogeneity in the available clinical evidence, we planned to undertake a narrative review and provide a precise summary of the role of vitamin D in COVID-19.

METHODS: PubMed/MEDLINE database was searched from inception till September 30, 2023 using appropriate MeSH terms. The initial search revealed 900 results. Thereafter, titles and abstracts were scanned and commentaries, letters, and editorials were excluded. Relevant observational studies and clinical trials/randomized controlled trials (RCTs) were full-text assessed and pertinent data were extracted for this narrative review.

KEY CONTENT AND FINDINGS: Data from observational and ecological studies suggest that hypovitaminosis D is associated with a higher risk of acquiring COVID-19. Similarly, evidence support a negative association between 25-hydroxyvitamin D levels and COVID-19 severity, nevertheless, causality remains to be established. With regard to vitamin D supplementation and COVID-19-related health outcomes, data from observational studies and RCTs are contradictory. Even in moderate-to-severe/severe COVID-19, vitamin D supplementation has not been shown to be beneficial. Besides, data suggest that vitamin D levels might alter COVID-19 vaccine efficacy and be associated with long COVID.

CONCLUSIONS: Vitamin D deficiency is linked to an increased risk of acquiring SARS-CoV-2 infection and poor COVID-19 prognosis, however, available evidence with regard to improved clinical outcomes with vitamin D supplementation is inconsistent.}, } @article {pmid38124254, year = {2023}, author = {Wilk, P and Moran, V and Alperin, MNP and Bohn, T and Fagherazzi, G and Zeegers, MP and Ruiz-Castell, M}, title = {The role of multimorbidity and socio-economic characteristics as potential risk factors for Long Covid: evidence from the multilevel analysis of the Survey of Health, Ageing and Retirement in Europe's corona surveys (2020-2021).}, journal = {Age and ageing}, volume = {52}, number = {12}, pages = {}, pmid = {38124254}, issn = {1468-2834}, support = {HHSN271201300071C/AG/NIA NIH HHS/United States ; R01 AG052527/AG/NIA NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; P01 AG005842/AG/NIA NIH HHS/United States ; P01 AG008291/AG/NIA NIH HHS/United States ; P20 AG012815/AG/NIA NIH HHS/United States ; R21 AG025169/AG/NIA NIH HHS/United States ; R03 AG045301/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Humans ; Male ; Middle Aged ; Europe/epidemiology ; Multilevel Analysis ; Multimorbidity ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prospective Studies ; Risk Factors ; Socioeconomic Factors ; Surveys and Questionnaires ; Age Factors ; }, abstract = {BACKGROUND: A substantial proportion of individuals continue experiencing persistent symptoms following the acute stage of their Covid-19 illness. However, there is a shortage of population-based studies on Long Covid risk factors.

OBJECTIVE: To estimate the prevalence of Long Covid in the population of middle-aged and older Europeans having contracted Covid-19 and to assess the role of multimorbidity and socio-economic characteristics as potential risk factors of Long Covid.

METHODS: A population-based longitudinal prospective study involving a sample of respondents 50 years and older (n = 4,004) from 27 countries who participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe (SHARE), in particular the Corona Surveys. Analyses were conducted by a multilevel (random intercept) hurdle negative binomial model.

RESULTS: Overall, 71.6% (95% confidence interval = 70.2-73.0%) of the individuals who contracted Covid-19 had at least one symptom of Long Covid up to 12 months after the infection, with an average of 3.06 (standard deviation = 1.88) symptoms. There were significant cross-country differences in the prevalence of Long Covid and number of symptoms. Higher education and being a man were associated with a lower risk of Long Covid, whilst being employed was associated with a higher risk of having Long Covid. Multimorbidity was associated with a higher number of symptoms and older age was associated with a lower number of symptoms.

CONCLUSION: Our results provide evidence on the substantial burden of Long Covid in Europe. Individuals who contracted Covid-19 may require long-term support or further medical intervention, putting additional pressure on national health care systems.}, } @article {pmid38123689, year = {2023}, author = {da Silva, ALG and Vieira, LDP and Dias, LS and Prestes, CV and Back, GD and Goulart, CDL and Arena, R and Borghi-Silva, A and Trimer, R}, title = {Impact of long COVID on the heart rate variability at rest and during deep breathing maneuver.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22695}, pmid = {38123689}, issn = {2045-2322}, mesh = {Humans ; Heart Rate/physiology ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Autonomic Nervous System ; Heart ; }, abstract = {While the majority of individuals with coronavirus disease 2019 (COVID-19) recover completely, a significant percentage experience persistent symptom, which has been characterized as Long COVID and may be associated with cardiac and autonomic dysfunction. We evaluated heart rate variability (HRV) at rest and during deep-breathing (M-RSA) in patients with Long COVID. Case-control design involved 21 patients with Long COVID and 20 controls; the HRV was evaluated (POLAR system) at rest in the supine position and during M-RSA and expressed in time domain and non-linear analysis. In the supine position we found a reduction HRV measures in Long COVID' patients compared to controls for: Mean_iRR (p < 0.001), STD_iRR (p < 0.001); STD_HR (p < 0.001); SD1 (p < 0.001); SD2 (p < 0.001); alpha2 (p < 0.001). In the M-RSA we found reduction Mean_iRR (p < 0.001), STD_iRR (p < 0.001), STD_HR (p < 0.001), rMSSD (p < 0.001), RR_tri-index (p < 0.001) in Long COVID' patients except for highest Mean_HR p < 0.001. In conclusion, Long COVID reduced HRV at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control when symptoms of COVID-19 persist following initial recovery.}, } @article {pmid38123233, year = {2023}, author = {Singh, SJ and Daynes, E and McAuley, HJC and Raman, B and Greening, NJ and Chalder, T and Elneima, O and Evans, RA and Bolton, CE}, title = {Balancing the value and risk of exercise-based therapy post-COVID-19: a narrative review.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {32}, number = {170}, pages = {}, pmid = {38123233}, issn = {1600-0617}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Exercise Therapy/adverse effects ; Exercise ; Fatigue ; Dyspnea ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2.}, } @article {pmid38117308, year = {2024}, author = {da Silva, LNM and Filho, AGO and Guimarães, JB}, title = {Musculoskeletal manifestations of COVID-19.}, journal = {Skeletal radiology}, volume = {53}, number = {10}, pages = {2009-2022}, pmid = {38117308}, issn = {1432-2161}, mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Musculoskeletal Diseases/diagnostic imaging/etiology ; *SARS-CoV-2 ; }, abstract = {During the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected millions of people worldwide, with acute respiratory distress syndrome (ARDS) being the most common severe condition of pulmonary involvement. Despite its involvement in the lungs, SARS-CoV-2 causes multiple extrapulmonary manifestations, including manifestations in the musculoskeletal system. Several cases involving bone, joint, muscle, neurovascular and soft tissues were reported shortly after pandemic onset. Even after the acute infection has resolved, many patients experience persistent symptoms and a decrease in quality of life, a condition known as post-COVID syndrome or long COVID. COVID-19 vaccines have been widely available since December 2020, preventing millions of deaths during the pandemic. However, adverse reactions, including those involving the musculoskeletal system, have been reported in the literature. Therefore, the primary goal of this article is to review the main imaging findings of SARS-CoV-2 involvement in the musculoskeletal system, including acute, subacute, chronic and postvaccination manifestations.}, } @article {pmid38116720, year = {2024}, author = {Filip, I}, title = {Individuals with HIV are likely targets for long COVID.}, journal = {AIDS (London, England)}, volume = {38}, number = {2}, pages = {N3-N4}, doi = {10.1097/QAD.0000000000003793}, pmid = {38116720}, issn = {1473-5571}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *HIV Infections/complications ; }, } @article {pmid38116712, year = {2024}, author = {Logarbo, BP and Yang, M and Longo, MT and Kingry, C and Courseault, J}, title = {Long COVID and the diagnosis of underlying hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {16}, number = {8}, pages = {935-937}, doi = {10.1002/pmrj.13120}, pmid = {38116712}, issn = {1934-1563}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Ehlers-Danlos Syndrome/diagnosis/complications ; *Joint Instability/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid38116398, year = {2023}, author = {Cappelletti, G and Colombrita, C and Limanaqi, F and Invernizzi, S and Garziano, M and Vanetti, C and Moscheni, C and Santangelo, S and Zecchini, S and Trabattoni, D and Silani, V and Clerici, M and Ratti, A and Biasin, M}, title = {Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1285836}, pmid = {38116398}, issn = {1662-5102}, abstract = {INTRODUCTION: COVID-19 typically causes Q7 respiratory disorders, but a high proportion of patients also reports neurological and neuromuscular symptoms during and after SARSCoV-2 infection. Despite a number of studies documenting SARS-CoV-2 infection of various neuronal cell populations, the impact of SARS-CoV-2 exposure on motor neuronal cells specifically has not been investigated so far.

METHODS: Thus, by using human iPSC-derived motor neurons (iPSC-MNs) we assessed: (i) the expression of SARS-CoV-2 main receptors; (ii) iPSC-MN infectability by SARS-CoV-2; and (iii) the effect of SARS-CoV-2 exposure on iPSC-MN transcriptome.

RESULTS: Gene expression profiling and immunofluorescence (IF) analysis of the main host cell receptors recognized by SARS-CoV-2 revealed that all of them are expressed in iPSC-MNs, with CD147 and NRP1 being the most represented ones. By analyzing SARS-CoV-2 N1 and N2 gene expression over time, we observed that human iPSC-MNs were productively infected by SARS-CoV-2 in the absence of cytopathic effect. Supernatants collected from SARS-CoV-2-infected iPSC-MNs were able to re-infect VeroE6 cells. Image analyses of SARS-CoV-2 nucleocapsid proteins by IF confirmed iPSC-MN infectability. Furthermore, SARS-CoV-2 infection in iPSCMNs significantly altered the expression of genes (IL-6, ANG, S1PR1, BCL2, BAX, Casp8, HLA-A, ERAP1, CD147, MX1) associated with cell survival and metabolism, as well as antiviral and inflammatory response.

DISCUSSION: These results suggest for the very first time that SARS-CoV-2 can productively infect human iPSC-derived MNs probably by binding CD147 and NRP1 receptors. Such information will be important to unveil the biological bases of neuromuscular disorders characterizing SARS-CoV-2 infection and the so called long-COVID symptoms.}, } @article {pmid38115966, year = {2023}, author = {Shen, Q and Joyce, EE and Ebrahimi, OV and Didriksen, M and Lovik, A and Sævarsdóttir, KS and Magnúsdóttir, I and Mikkelsen, DH and Unnarsdóttir, AB and Hauksdóttir, A and Hoffart, A and Kähler, AK and Thórdardóttir, EB and Eythórsson, E and Frans, EM and Tómasson, G and Ask, H and Hardardóttir, H and Jakobsdóttir, J and Lehto, K and Lu, L and Andreassen, OA and Sullivan, PF and Pálsson, R and Erikstrup, C and Ostrowski, SR and Werge, T and Aspelund, T and Pedersen, OBV and Johnson, SU and Fang, F and Valdimarsdóttir, UA}, title = {COVID-19 illness severity and 2-year prevalence of physical symptoms: an observational study in Iceland, Sweden, Norway and Denmark.}, journal = {The Lancet regional health. Europe}, volume = {35}, number = {}, pages = {100756}, pmid = {38115966}, issn = {2666-7762}, abstract = {BACKGROUND: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19.

METHODS: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis.

FINDINGS: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis.

INTERPRETATION: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms.

FUNDING: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.}, } @article {pmid38114867, year = {2024}, author = {Le, GH and Kwan, ATH and Wong, S and Guo, Z and Teopiz, KM and Badulescu, S and Meshkat, S and d'Andrea, G and Ho, R and Rhee, TG and Cao, B and Phan, L and Rosenblat, JD and Mansur, RB and Subramaniapillai, M and McIntyre, RS}, title = {Impact of Elevated Body Mass Index (BMI) on Hedonic Tone in Persons with Post-COVID-19 Condition: A Secondary Analysis.}, journal = {Advances in therapy}, volume = {41}, number = {2}, pages = {686-695}, pmid = {38114867}, issn = {1865-8652}, mesh = {Humans ; Infant ; Body Mass Index ; *COVID-19/complications ; Obesity/complications ; Pleasure ; Self Report ; }, abstract = {INTRODUCTION: The post-COVID-19 condition (PCC) is characterized by persistent, distressing symptoms following an acute COVID-19 infection. These symptoms encompass various domains, including hedonic tone, which is critical for overall well-being. Furthermore, obesity is both a risk factor for COVID-19 and PCC and associated with impaired hedonic tone. This study aims to investigate whether elevated body mass index (BMI) is associated with hedonic tone in persons with PCC.

METHODS: We perform a post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial investigating the impact of vortioxetine on cognitive impairment in persons with PCC. Statistical analysis of baseline data using a generalized linear model was undertaken to determine the relationship of BMI to hedonic tone measured by Snaith-Hamilton Pleasure Scale (SHAPS) scores. The model was adjusted for covariates including age, sex, race, suspected versus confirmed COVID-19 cases, alcohol amount consumed per week, and annual household income.

RESULTS: The baseline data of 147 participants were available for analysis. BMI had a statistically significant positive association with baseline SHAPS total scores (β = 0.003, 95% CI [6.251E-5, 0.006], p = 0.045), indicating elevated BMI is associated with deficits in self-reported reward system functioning.

CONCLUSION: Higher BMI is associated with greater deficits in hedonic tone in persons with PCC, which may impact reward functioning processes such as reward prediction and processing. The mediatory effect of BMI on reward function underscores the need to investigate the neurobiologic interactions to elucidate preventative and therapeutic interventions for persons with PCC. Therapeutic development targeting debilitating features of PCC (e.g., motivation, cognitive dysfunction) could consider stratification on the basis of baseline BMI.

TRIAL REGISTRATION NUMBER: NCT05047952.}, } @article {pmid38114835, year = {2024}, author = {Hall, S}, title = {Vaccines reduce the risk of long COVID in children.}, journal = {Nature}, volume = {625}, number = {7994}, pages = {227}, pmid = {38114835}, issn = {1476-4687}, mesh = {Child ; Humans ; *COVID-19 Vaccines ; *Disease Susceptibility ; *Post-Acute COVID-19 Syndrome/epidemiology/prevention & control ; mRNA Vaccines ; United States/epidemiology ; }, } @article {pmid38114255, year = {2023}, author = {Altmann, DM and Pagel, C}, title = {Long covid: where are we, what does it say about our pandemic response, and where next?.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2972}, doi = {10.1136/bmj.p2972}, pmid = {38114255}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; *COVID-19 ; }, } @article {pmid38113577, year = {2024}, author = {Fujita, K and Iwata, T and Kanai, O and Hata, H and Tanaka, H and Imakita, T and Oi, I and Odagaki, T and Aoyama, A and Sawai, S and Mio, T}, title = {Clinical features of pneumothorax associated with COVID-19: A retrospective analysis of two centres.}, journal = {Respiratory investigation}, volume = {62}, number = {1}, pages = {137-141}, doi = {10.1016/j.resinv.2023.12.001}, pmid = {38113577}, issn = {2212-5353}, mesh = {Humans ; Male ; Aged ; Female ; *COVID-19/complications ; Retrospective Studies ; SARS-CoV-2 ; *Pneumothorax/etiology/therapy ; *Diabetes Mellitus, Type 2/complications ; COVID-19 Testing ; }, abstract = {BACKGROUND: Pneumothorax is a known sequela of coronavirus disease 2019 (COVID-19). However, the clinical features of pneumothorax associated with COVID-19 have not been fully elucidated.

METHODS: Patients who developed pneumothorax within 6 months of being diagnosed with COVID-19 were retrospectively analysed at two institutions. We investigated the background factors, COVID-19 severity and treatment, timing of pneumothorax onset, treatment modalities, treatment duration, and prognosis of these patients.

RESULTS: A total of 21 patients were diagnosed with pneumothorax within 6 months of COVID-19 diagnosis. The combined incidence rate of pneumothorax at two institutions was 0.89 %. The mean age of these patients was 72.5 years, and they were predominantly male (90.5 %), with a history of smoking (76.1 %). The most frequent comorbidity was hypertension, followed by type 2 diabetes mellitus, COPD, and malignancy. Approximately 76 % of the patients had moderate or severe disease requiring oxygenation. Moreover, 90.5 % of these patients were taking antiviral drugs; 52.4 %, immunosuppressant agents (baricitinib/tocilizumab); and 66.7 % were on dexamethasone. The median time to the onset of pneumothorax was 15.0 days, and 86 % of cases occurred within 1 month of COVID-19 diagnosis. Bilateral pneumothorax and pneumomediastinum were noted in one patient each. Chest drainage was performed in 71.4 % of the patients. The mean treatment duration for pneumothorax was 14.1 days, and the 30-day mortality rate was 28.6 %.

CONCLUSION: Pneumothorax associated with COVID-19 was more common in patients with moderate or severe disease requiring oxygenation, and occurred within 1 month of COVID-19 diagnosis. Pneumothorax associated with COVID-19 is a serious complication with a high mortality rate and clinicians should pay attention to it.}, } @article {pmid38113020, year = {2024}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Catahay, JA and Macasaet, R and Velasco, JV and Macapagal, S and Caldararo, M and Henry, BM and Lippi, G and Franco-Moreno, A and Notarte, KI}, title = {Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.}, journal = {Infection}, volume = {52}, number = {1}, pages = {43-58}, pmid = {38113020}, issn = {1439-0973}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Ritonavir ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Dexamethasone/therapeutic use ; *Metformin ; }, abstract = {PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID.

METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool.

RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID.

CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.}, } @article {pmid38112945, year = {2023}, author = {Micheletti, C and Medori, MC and Dhuli, K and Maltese, PE and Cecchin, S and Bonetti, G and Fioretti, F and Assoni, L and Calzoni, A and Praderio, A and De Angelis, MG and Donato, K and Arabia, G and Lorusso, L and Manganotti, P and Capelli, E and Marceddu, G and Bertelli, M and Nodari, S}, title = {Linking pathogenic and likely pathogenic gene variants to long-COVID symptoms.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6 Suppl}, pages = {20-32}, doi = {10.26355/eurrev_202312_34686}, pmid = {38112945}, issn = {2284-0729}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; SARS-CoV-2/genetics ; Genetic Testing/methods ; Genetic Predisposition to Disease ; }, abstract = {OBJECTIVE: Long-COVID is a clinical syndrome characterized by the presence of symptoms related to SARS-CoV-2 infection that persist for at least four weeks after recovery from COVID-19. Genetics have been proposed to play an important role in long-COVID syndrome onset. This study aimed to identify genetic pathogenetic and likely pathogenetic causative variants of Mendelian genetic diseases in patients with Long-COVID syndrome. Additionally, we aimed to establish an association between these genetic variants and the clinical symptoms manifested during long-COVID syndrome.

PATIENTS AND METHODS: 95 patients affected by long-COVID syndrome were analyzed with a Next-Generation Sequencing (NGS) panel comprising 494 genes. The analyzed genes and the symptoms of the patients collected with an ad-hoc questionnaire were divided into four groups (cardiological, respiratory, immunological, and neurological). Finally, a statistical analysis comprising descriptive statistics, classification based on reported symptoms, and comparative analysis against a control group of healthy individuals was conducted.

RESULTS: 12 patients resulted positive for genetic testing with an autosomal dominance (8) or autosomal recessive (4) inheritance, showing a higher prevalence of cardiovascular genetic diseases (9) in the analyzed cohort compared to the normal population. Moreover, the onset of the long-COVID syndrome and its cardiovascular manifestations was compliant with the onset reported in the literature for the identified genetic diseases, suggesting that COVID-19 could manifest late-onset genetic diseases associated with their appearance. Apart from the 12 positive patients, 57 were healthy carriers of genetic diseases. Analyzing the whole cohort, a statistical correlation between prevalent symptomatology and the gene class was established, suggesting an association between the genetic susceptibility of an individual and the possibility of developing specific long-COVID syndrome symptoms, especially cardiovascular symptoms. Furthermore, 17 genetic variants were identified in CFTR. Finally, we identified genetic variants in IFNAR2 and POLG, supporting their respective involvement in inflammation and mitochondria mechanisms, correlated with long-COVID syndrome according to literature data.

CONCLUSIONS: This study proposed COVID-19 to act as a manifest of underlying late-onset genetic diseases Mendelian associated with carrier status. Moreover, according to our results, mutations in cardiological genes are more present in patients who show cardiological symptoms during the syndrome. This underscores the necessity for cardiological investigation and genetic screening in long-COVID patients to address existing or potential clinical implications.}, } @article {pmid38112944, year = {2023}, author = {Dhuli, K and Medori, MC and Micheletti, C and Donato, K and Fioretti, F and Calzoni, A and Praderio, A and De Angelis, MG and Arabia, G and Cristoni, S and Nodari, S and Bertelli, M}, title = {Presence of viral spike protein and vaccinal spike protein in the blood serum of patients with long-COVID syndrome.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6 Suppl}, pages = {13-19}, doi = {10.26355/eurrev_202312_34685}, pmid = {38112944}, issn = {2284-0729}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Serum ; *COVID-19 ; Proteomics ; Spike Glycoprotein, Coronavirus ; Vaccination ; *Vaccines ; }, abstract = {OBJECTIVE: COVID-19 patients experience, in 10-20% of the cases, a prolonged long-COVID syndrome, defined as the persistence of symptoms for at least two months after the infection. The underlying biological mechanisms of this syndrome remain poorly understood. Several hypotheses have been proposed, among which are the potential autoimmunity resulting from molecular mimicry between viral spike protein and human proteins, the reservoir and viral reproduction hypothesis, and the viral integration hypothesis. Although official data state that vaccinal spike protein is harmless and remains at the site of infection, several studies proposed spike protein toxicity and found it in blood circulation several months after the vaccination. To search for the presence of viral and vaccine spike protein in a cohort of long-COVID patients.

PATIENTS AND METHODS: In this study, we employed a proteomic-based approach utilizing mass spectrometry to analyze the serum of 81 patients with long-COVID syndrome. Moreover, viral integration in patients' leukocytes was assessed with a preliminary study, without further investigation.

RESULTS: We identified the presence of the viral spike protein in one patient after infection clearance and negativity of COVID-19 test and the vaccine spike protein in two patients two months after the vaccination.

CONCLUSIONS: This study, in agreement with other published investigations, demonstrates that both natural and vaccine spike protein may still be present in long-COVID patients, thus supporting the existence of a possible mechanism that causes the persistence of spike protein in the human body for much longer than predicted by early studies. According to these results, all patients with long-COVID syndrome should be analyzed for the presence of vaccinal and viral spike protein.}, } @article {pmid38112943, year = {2023}, author = {Medori, MC and Dhuli, K and Tezzele, S and Micheletti, C and Maltese, PE and Cecchin, S and Bonetti, G and Fioretti, F and Calzoni, A and Praderio, A and De Angelis, MG and Arabia, G and Donato, K and Lorusso, L and Manganotti, P and Capelli, E and Cristoni, S and Nodari, S and Bertelli, M}, title = {Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {6 Suppl}, pages = {1-12}, doi = {10.26355/eurrev_202312_34684}, pmid = {38112943}, issn = {2284-0729}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Proteomics ; Pandemics ; *COVID-19 ; Biomarkers ; Natriuretic Peptides ; }, abstract = {OBJECTIVE: The highly transmissible severe acute respiratory syndrome-Coronavirus-2 was responsible for the 2020 COVID-19 pandemic. COVID-19 mostly affects the respiratory system; however, this infection also affects several other organs. In addition, the sequelae of this disease affect patients for several months after recovery, resulting in long-COVID syndrome.

PATIENTS AND METHODS: In order to characterize the differences between healthy control individuals and long-COVID patients, proteomic profiling of the serum of both groups was performed by mass spectrometry. The obtained data were analyzed with multivariate and univariate statistical analyses.

RESULTS: Initially, performing a partial latent square discriminant analysis (PLS-DA) made it possible to identify thirty-three proteins of interest, which were then subjected to a receiver operating characteristic (ROC) analysis. Four proteins were identified as potential stand-alone biomarkers: Sirtuin 1, Natriuretic Peptide B, Hemopexin, and Arachidonate 5-Lipoxygenase. Moreover, a multivariate ROC analysis identified a panel of biomarkers composed of Natriuretic Peptide B, Anterior Gradient 2 Protein, Adiponectin, Endothelin Converting Enzyme 1, Interferon Induced Transmembrane Protein 1, Mannose Binding Lectin 2, Prostaglandin-Endoperoxide Synthase 2, Pirin, Prostaglandin Reductase 1 and Cystatin C.

CONCLUSIONS: The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Nevertheless, these data should be validated in a larger cohort.}, } @article {pmid38112761, year = {2024}, author = {Wu, JY and Liu, MY and Hsu, WH and Tsai, YW and Liu, TH and Huang, PY and Chuang, MH and Chin, SE and Lai, CC}, title = {Association between vitamin D deficiency and post-acute outcomes of SARS-CoV-2 infection.}, journal = {European journal of nutrition}, volume = {63}, number = {2}, pages = {613-622}, pmid = {38112761}, issn = {1436-6215}, mesh = {Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; Emergency Room Visits ; *Vitamin D Deficiency/complications/epidemiology ; Vitamin D ; }, abstract = {OBJECTIVES: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

METHODS: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19.

RESULTS: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually.

CONCLUSION: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase.}, } @article {pmid38112577, year = {2024}, author = {Bergmans, RS and Clauw, DJ and Flint, C and Harris, H and Lederman, S and Schrepf, A}, title = {Chronic overlapping pain conditions increase the risk of long COVID features, regardless of acute COVID status.}, journal = {Pain}, volume = {165}, number = {5}, pages = {1112-1120}, pmid = {38112577}, issn = {1872-6623}, support = {//Tonix Pharmaceuticals Inc./ ; }, mesh = {Humans ; *Chronic Pain/epidemiology ; Post-Acute COVID-19 Syndrome ; *Influenza, Human ; Retrospective Studies ; *COVID-19 ; Chronic Disease ; }, abstract = {Chronic overlapping pain conditions (COPCs) refer to conditions that have similar central nervous system pathophysiologic mechanisms driving widespread pain as well as common comorbid symptoms such as fatigue and problems with sleep, memory, and mood. If COPCs predict the onset of long COVID, this could offer a valuable orientation for long COVID-related research and clinical care. This retrospective cohort study aimed to determine whether having a COPC predicts the onset of long COVID features using US electronic health records and 1:1 propensity score matching without replacement. The study cohorts included (1) people with acute COVID (n = 1,038,402), (2) people with acute influenza (n = 262,092), and (3) a noninfected cohort comprising people with a routine healthcare encounter (n = 1,081,593). Having a COPC increased the risk of long COVID features in all 3 study cohorts. Among those with COVID, having a pre-existing COPC increased the risk by 1.47 (95% CI = 1.46, 1.47). In the influenza cohort, COPCs increased the risk by 1.39 (95% CI = 1.38, 1.40). In the noninfected cohort, COPCs increased the risk by 1.57 (95% CI = 1.56, 1.59). These findings reinforce the likelihood that nociplastic mechanisms play a prominent role in long COVID. Recognizing that this ubiquitous nonspecific syndrome occurs frequently in the population can inform precision medicine therapies that avoid the pitfalls of viewing long COVID exclusively in the framework of postinfectious disease.}, } @article {pmid38112241, year = {2024}, author = {Thomas, B and Pattinson, R and Edwards, D and Dale, C and Jenkins, B and Lande, H and Bundy, C and Davies, JL}, title = {Definitions and measures of long COVID fatigue in adults: a scoping review protocol.}, journal = {JBI evidence synthesis}, volume = {22}, number = {3}, pages = {481-488}, doi = {10.11124/JBIES-23-00277}, pmid = {38112241}, issn = {2689-8381}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue ; Review Literature as Topic ; }, abstract = {OBJECTIVE: The aim of this scoping review is to investigate how fatigue is defined and measured in adults with long COVID.

INTRODUCTION: Following COVID-19 infection, 10% to 20% of individuals experience persisting symptoms for a minimum of 3 months; this is commonly known as long COVID. Fatigue is one of the most prevalent symptoms of long COVID, but there is currently no consistently applied definition of long COVID fatigue. To advance our understanding of long COVID fatigue, we must first identify the current definitions and measures being used to describe and mesure this condition.

INCLUSION CRITERIA: This review will consider published and unpublished studies involving adults (≥18 years) that define and/or measure long COVID fatigue. Papers using quantitative or qualitative designs will be included. Conference abstracts, editorials, and opinion papers will be excluded.

METHODS: Published studies from January 2020 onwards will be searched for across MEDLINE (Ovid), CINAHL (EBSCOhost), Embase (Ovid), Scopus, PsycINFO (Ovid), Web of Science Core Collection, Epistemonikos, and Cochrane Central Register of Controlled Trials (CENTRAL). Dimensions, Overton, and ProQuest Dissertations and Theses will be searched for unpublished literature. Eligible records will be de-duplicated, and 2 independent reviewers will carry out title, abstract, and full-text screening. A data extraction tool will be pilot tested on a small number of papers, then modified as necessary, with any modifications detailed in the scoping review. Findings will be presented in tables and charts, supported by a narrative summary.

REVIEW REGISTRATION: Open Science Framework https://osf.io/hnf8z.}, } @article {pmid38112151, year = {2023}, author = {Kapusta, J and Babicki, M and Pieniawska-Śmiech, K and Kałuzińska-Kołat, Ż and Kołat, D and Jankowski, P and Kasprzak, JD and Wejner-Mik, P and Bianek-Bodzak, A and Chudzik, M}, title = {Clinical and electrocardiographic correlates of myocardial dysfunction after COVID-19 in nonhospitalised patients in long-term follow-up. Data from the polish long-covid cardiovascular study.}, journal = {Journal of medical virology}, volume = {95}, number = {12}, pages = {e29331}, doi = {10.1002/jmv.29331}, pmid = {38112151}, issn = {1096-9071}, support = {//The Medical Centre of Postgraduate Education/ ; }, mesh = {Humans ; Male ; Middle Aged ; Blood Pressure Monitoring, Ambulatory ; *Cardiomyopathies ; *COVID-19/complications ; Electrocardiography/methods ; Follow-Up Studies ; Heart/diagnostic imaging ; Poland/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Female ; Adult ; }, abstract = {Clinical evidence indicates that COVID-19 is a multiorgan disease that significantly impacts the cardiovascular system. However, little is known about the predictors of myocardial dysfunction after SARS-CoV-2 infection. Therefore, this research aimed to evaluate the clinical and electrocardiographic correlates of myocardial dysfunction after SARS-CoV-2 infection in nonhospitalised patients without previously diagnosed cardiovascular disease. This observational study included 448 patients selected from the database of 4142 patients in the Polish Long-Covid Cardiovascular study. All patients underwent a 12-lead electrocardiogram (ECG); 24-h Holter ECG monitoring, 24/7 ambulatory blood pressure monitoring, echocardiography, and cardiac magnetic resonance imaging. According to the results of diagnostic tests, patients were divided into two groups depending on the occurrence of myocardial dysfunction after COVID-19. Group 1-without myocardial dysfunction after COVID-19-consisted of 419 patients, with a mean age of 48.82 (SD ± 11.91), and Group 2 (29 patients)-with myocardial dysfunction after COVID-19, with a mean age of 51.45 (SD ± 12.92). When comparing the analysed groups, there were significantly more men in Group 2 (p = 0.006). QRS (corresponds to the time of ventricular contraction in an electrocardiographic examination) fragmentation (p = 0.031), arrhythmias (atrial fibrillation, supraventricular extrasystole, ventricular extrasystole) (p = 0.008), and male gender (p = 0.007) were independently associated with myocardial dysfunction after COVID-19. The study showed that myocardial damage after COVID-19 affects men more often and is independent of typical clinical factors and the severity of the disease course. The QRS fragmentation and arrhythmias observed in the ECG indicate the possibility of myocardial dysfunction in patients after COVID-19, which may be a valuable marker for physicians.}, } @article {pmid38111916, year = {2023}, author = {Derrick, J and Patterson, B and Bai, J and Wang, J}, title = {A Mechanistic Model for Long COVID Dynamics.}, journal = {Mathematics (Basel, Switzerland)}, volume = {11}, number = {21}, pages = {}, pmid = {38111916}, issn = {2227-7390}, support = {R15 GM152943/GM/NIGMS NIH HHS/United States ; }, abstract = {Long COVID, a long-lasting disorder following an acute infection of COVID-19, represents a significant public health burden at present. In this paper, we propose a new mechanistic model based on differential equations to investigate the population dynamics of long COVID. By connecting long COVID with acute infection at the population level, our modeling framework emphasizes the interplay between COVID-19 transmission, vaccination, and long COVID dynamics. We conducted a detailed mathematical analysis of the model. We also validated the model using numerical simulation with real data from the US state of Tennessee and the UK.}, } @article {pmid38111277, year = {2024}, author = {Little, J and Higgins, M and Palepu, R}, title = {Long COVID - Can we deny a diagnosis without denying a person's reality?.}, journal = {Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists}, volume = {32}, number = {1}, pages = {44-46}, doi = {10.1177/10398562231222809}, pmid = {38111277}, issn = {1440-1665}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Emotions ; COVID-19 Testing ; }, abstract = {OBJECTIVE: The aim is to consider Long COVID not as a new clinical entity but as another example of a disabling, historical phenomenon.

CONCLUSIONS: A triad of polymorphic symptomatology, an elusive pathophysiological explanation and a hostile defensiveness has appeared throughout history. The reluctance to consider these contextually may delay early intervention and appropriate patient care.}, } @article {pmid38110928, year = {2023}, author = {Khachidze, N and Manjavidze, T and Anda, EE and Nedberg, IH and Sandøy, IF and Rylander, C}, title = {The impact of COVID-19-related restrictions on pregnancy and abortion rates in the Republic of Georgia.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {1435}, pmid = {38110928}, issn = {1472-6963}, mesh = {Pregnancy ; Female ; Humans ; Georgia (Republic)/epidemiology ; Georgia ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Communicable Disease Control ; *Abortion, Induced ; }, abstract = {BACKGROUND: The Republic of Georgia implemented COVID-19-related restrictions starting on 31 March 2020, when it imposed a 1-month strict lockdown, after which the country continued with some form of restrictions for 1 year. These restrictions created barriers to healthcare access, affected healthcare services, caused severe economic degradation, and changed reproductive behavior. The aim of this study was to explore the impact of COVID-19-related restrictions on pregnancy and abortion rates in Georgia.

METHODS: Information on pregnancy, abortion, and related variables was extracted from the Georgian Birth Registry from January 2018 through April 2022. The final study sample included 232,594 pregnancies and 86,729 abortions. We used interrupted time series analysis to study the impact of COVID-19-related restrictions.

RESULTS: There were slightly decreasing trends in pregnancy and abortion rates in the pre-pandemic period (1 January 2018-31 March 2020). During the 1-month strict lockdown (1 April-30 April 2020), pregnancy and abortion rates decreased in all investigated age groups. There were no substantial differences in pregnancy or abortion rates in the pandemic period (for pregnancies: 1 April 2020-30 June 2021; for abortions: 1 April 2020-30 April 2022) compared to the pre-pandemic period. The precision of all estimates suggested that both small increases and decreases in pregnancy and abortion rates are reasonably compatible with our data.

CONCLUSIONS: Despite the 1-year-long COVID-19-related restrictions, our results did not indicate substantial long-term changes in pregnancy or abortion rates during the study period for any age group. This may indicate that the restrictions did not substantially influence access to contraception, abortion services, or reproductive behavior.}, } @article {pmid38110069, year = {2023}, author = {Zheng, C and Huang, WY and Sun, FH and Wong, MC and Siu, PM and Chen, XK and Wong, SH}, title = {Association of Sedentary Lifestyle with Risk of Acute and Post-Acute COVID-19 Sequelae: A Retrospective Cohort Study.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2023.12.002}, pmid = {38110069}, issn = {1555-7162}, abstract = {BACKGROUND: Evidence suggests that coronavirus disease 2019 (COVID-19) survivors could experience COVID-19 sequelae. Although various risk factors for COVID-19 sequelae have been identified, little is known about whether a sedentary lifestyle is an independent risk factor.

METHODS: In this retrospective cohort study, 4850 participants self-reported their COVID-19 sequelae symptoms between June and August 2022. A sedentary lifestyle included physical inactivity (<150 min/week of moderate-to-vigorous intensity physical activity) and prolonged sedentary behavior (≥10 h/day) before the fifth COVID-19 wave was recorded. Logistic regression analysis was performed to determine the relationships between sedentary lifestyle and risk of acute and post-acute (lasting ≥2 months) COVID-19 sequelae.

RESULTS: A total of 1443 COVID-19 survivors and 2962 non-COVID-19 controls were included. Of the COVID-19 survivors, >80% and >40% self-reported acute and post-acute COVID-19 sequelae, respectively. In the post-acute phase, COVID-19 survivors who were physically inactive had a 37% lower risk of insomnia, whereas those with prolonged sedentary behavior had 25%, 67%, and 117% higher risks of at least one symptom, dizziness, and "pins and needles" sensation, respectively. For the acute phase, prolonged sedentary behavior was associated with a higher risk of fatigue, "brain fog," dyspnea, muscle pain, joint pain, dizziness, and "pins and needles" sensation. Notably, sedentary behavior, rather than physical inactivity, was correlated with a higher risk of severe post-COVID-19 sequelae in both acute and post-acute phases.

CONCLUSIONS: Prolonged sedentary behavior was independently associated with a higher risk of both acute and post-acute COVID-19 sequelae, whereas physical inactivity played contradictory roles in COVID-19 sequelae.}, } @article {pmid38109748, year = {2023}, author = {Jirmanus, LZ and Schwartzmann, EG and Davids, JD and Gullette, MM and Killick, C}, title = {Universal Masking in Health Care Settings.}, journal = {Annals of internal medicine}, volume = {176}, number = {12}, pages = {eL230350}, doi = {10.7326/L23-0350}, pmid = {38109748}, issn = {1539-3704}, mesh = {Humans ; *COVID-19 ; Delivery of Health Care ; SARS-CoV-2 ; }, } @article {pmid38107643, year = {2023}, author = {Wormgoor, MEA and Rodenburg, SC}, title = {Focus on post-exertional malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deterioration.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1247698}, pmid = {38107643}, issn = {1664-2295}, abstract = {BACKGROUND: Post-exertional malaise (PEM) is considered a hallmark characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This may also apply to subgroups of patients with long COVID-induced ME/CFS. However, it is uncertain to what extent PEM is acknowledged in routine specialist healthcare for ME/CFS patients, and how this affects patient outcomes.

OBJECTIVE: This study aims to evaluate to what extent ME/CFS patients experienced focus on PEM in specialist healthcare practice and its significance for outcome and care quality.

METHODS: Data from two online cross-sectional surveys covering specialist healthcare services for ME/CFS patients at rehabilitation institutes in Norway and two regional hospitals, respectively, were analyzed. Evaluations of 788 rehabilitation stays, 86 hospital consultations, and 89 hospital interventions were included. Logistic regression models and Mann-Whitney U-tests were used to quantify the impact of addressing PEM on health and functioning, care satisfaction, or benefit. Spearman's rank correlation and Cronbach's alpha of focus on PEM with the respondents' perception of healthcare providers' knowledge, symptom acknowledgment, and suitability of intervention were assessed as measures for care quality and their internal consistency, respectively.

RESULTS: PEM was addressed in 48% of the rehabilitation stays, 43% of the consultations, and 65% of the hospital interventions. Failure to address PEM roughly doubled the risk of health deterioration, following rehabilitation (OR = 0.39, 95% CI 0.29-0.52; 40.1% vs. 63.2% P = <0.001) and hospital intervention (OR = 0.34, 95% CI 0.13-0.89; 22.4% vs. 45.2%, p = 0.026). The focus on PEM (PEM-focus) during the clinical contact was associated with significantly higher scores on patients' rated care satisfaction and benefit of both consultation and intervention. Furthermore, addressing PEM was (inter)related to positive views about healthcare providers' level of knowledge of ME/CFS, their acknowledgment of symptoms, obtained knowledge, and the perceived suitability of intervention (Cronbach's alpha ≥0.80).

DISCUSSION: PEM is still frequently not acknowledged in specialist healthcare practice for ME/CFS patients in Norway. Not addressing PEM substantially increased the probability of a decline in health and functioning following the intervention and was strongly associated with reduced perceived care quality, satisfaction, and benefit. These findings may be related to the applied explanatory models for ME/CFS and are most likely of relevance to long COVID.}, } @article {pmid38107625, year = {2023}, author = {Laneri, A and Cerri, S and Della Casa, G and Moretti, A and Manfredi, A and Sebastiani, M and Clini, E and Salvarani, C}, title = {COVID-19, A New Possible Mimicker of Interstitial Lung Disease Related to Primary Sjögren's Syndrome.}, journal = {Case reports in medicine}, volume = {2023}, number = {}, pages = {9915553}, pmid = {38107625}, issn = {1687-9627}, abstract = {Introduction. Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases. Case Report. In 2018, a 52-year-old woman, was diagnosed with primary Sjogren's syndrome (pSS). The patient did not show respiratory symptoms, and a chest X-ray was normal. During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest high-resolution computed tomography (HRCT) showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFTs) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist did not allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A "wait and see" approach was decided, monitoring clinical conditions, PFTs, and chest HRCT over time. Only 2 years after the hospitalization, improvement of clinical symptoms was reported; PFT also improved, and HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations. Discussion. In the above-reported case report, 3 differential diagnoses were possible: a COVID-19-related ILD, a preexisting pSS-ILD, or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations disappeared 2 years later.}, } @article {pmid38107020, year = {2024}, author = {Rizzi, G and Pacifico, D and Sabatini, S and Annoni, AM and Mele, F and Jovic, S and Piccoli, L and Corna, L and Amati, R and Pertoldi, W and Fiordelli, M and Sallusto, F and Albanese, E}, title = {SARS-CoV-2 infection and cognition in community-dwelling and nursing home residents in southern Switzerland.}, journal = {Brain, behavior, & immunity - health}, volume = {35}, number = {}, pages = {100701}, pmid = {38107020}, issn = {2666-3546}, abstract = {BACKGROUND: COVID-19 patients can report 'brain fog' and may exhibit cognitive symptoms for months after recovery (Cognitive COVID). However, evidence on whether and the extent to which SARS-CoV-2 infection impacts cognition irrespective of COVID-19 course and severity is limited to clinical samples and mainly comes from prognostic studies. We aimed to explore the association between serologically confirmed SARS-CoV-2 infection and cognitive functioning in community-based and institutionalized older adults, irrespective of COVID-19 symptoms.

METHODS: We conducted a case-control study nested into two cohorts in Southern Switzerland. Eligible subjects were Italian speaking older adults, without a previous diagnosis of dementia, who underwent serological testing for anti-SARS-CoV-2 antibodies between November 2020 and July 2021. We manually selected age-, sex- and education-matched cases (i.e., individuals with a serologically confirmed SARS-CoV-2 infection), with seronegative controls, and we conducted in-person neuropsychological assessments using validated, highly sensitive cognitive tests.

RESULTS: We completed 38 neuropsychological assessments in a mostly female sample of older adults (Mean age: 83.13 ± 8.95; 86.8% women). 17 were community dwelling individuals while 21 lived in a nursing home. As expected, socio-demographic characteristics of age, gender and educational level were similarly distributed between cases (n = 14) and controls (n = 24). In linear regression models, cases had significantly lower scores in cognitive tasks of memory (β = -0.367, p = 0.023), attention (β = 0.428, p = 0.008) and executive functions (β = 0.326, p = 0.046). We found no significant difference in tests of language and spatial-temporal orientation (all p values > 0.05).

CONCLUSIONS: SARS-CoV-2 infection was associated with cognitive impairment in memory, attention, and executive functions in older adults. Our findings are consistent with mechanistic evidence of the neurotropism of the virus and provide empirical support for the "Cognitive COVID" construct also in non-clinical samples. With nearly 800 million COVID-19 cases (in April 2023), and many more infections worldwide, the clinical and public health implications of Cognitive COVID due to SARS-CoV-2 infection may be massive and warrant further epidemiological investigations.}, } @article {pmid38106559, year = {2023}, author = {Vivaldi, G and Pfeffer, PE and Talaei, M and Basera, TJ and Shaheen, SO and Martineau, AR}, title = {Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.}, journal = {EClinicalMedicine}, volume = {65}, number = {}, pages = {102251}, pmid = {38106559}, issn = {2589-5370}, abstract = {BACKGROUND: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

METHODS: COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16 potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

FINDINGS: We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI.

INTERPRETATION: Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens.

FUNDING: Barts Charity.}, } @article {pmid38106125, year = {2023}, author = {Rahman, A and Russell, M and Zheng, W and Eckrich, D and Ahmed, I}, title = {SARS-CoV-2 Infection is Associated with an Increase in New Diagnoses of Schizophrenia Spectrum and Psychotic Disorder: A Study Using the US National COVID Cohort Collaborative (N3C).}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38106125}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001857/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Amid the ongoing global repercussions of SARS-CoV-2, it's crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-positive (n = 219,264), and COVID-negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.}, } @article {pmid38105936, year = {2023}, author = {El-Toukhy, S and Hegeman, P and Zuckerman, G and Anirban, RD and Moses, N and Troendle, JF and Powell-Wiley, TM}, title = {A prospective natural history study of post acute sequalae of COVID-19 using digital wearables: Study protocol.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38105936}, issn = {2693-5015}, support = {ZIA MD000011/ImNIH/Intramural NIH HHS/United States ; }, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is characterized by having 1 + persistent, recurrent, or emergent symptoms post the infection's acute phase. The duration and symptom manifestation of PASC remain understudied in nonhospitalized patients. Literature on PASC is primarily based on data from hospitalized patients where clinical indicators such as respiratory rate, heart rate, and oxygen saturation have been predictive of disease trajectories. Digital wearables allow for a continuous collection of such physiological parameters. This protocol outlines the design, aim, and procedures of a natural history study of PASC using digital wearables.

METHODS: This is a single-arm, prospective, natural history study of a cohort of 550 patients, ages 18 to 65 years old, males or females who own a smartphone and/or a tablet that meets pre-determined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a healthcare professional or organization within 5 days before enrollment. The study aims to identify wearables collected physiological parameters that are associated with PASC in patients with a positive diagnosis. The primary endpoint is long COVID-19, defined as ≥ 1 symptom at 3 weeks beyond first symptom onset or positive diagnosis, whichever comes first. The secondary endpoint is chronic COVID-19, defined as ≥ 1 symptom at 12 weeks beyond first symptom onset or positive diagnosis. We hypothesize that physiological parameters collected via wearables are associated with self-reported PASC. Participants must be willing and able to consent to participate in the study and adhere to study procedures for six months.

DISCUSSION: This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. Given evidence on key demographics and risk profiles associated with PASC, the study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of use of wearables as population-level monitoring health tools for communicable diseases.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04927442.}, } @article {pmid38105651, year = {2024}, author = {Thurgur, H and Lynskey, M and Schlag, AK and Croser, C and Nutt, DJ and Iveson, E}, title = {Feasibility of a cannabidiol-dominant cannabis-based medicinal product for the treatment of long COVID symptoms: A single-arm open-label feasibility trial.}, journal = {British journal of clinical pharmacology}, volume = {90}, number = {4}, pages = {1081-1093}, doi = {10.1111/bcp.15988}, pmid = {38105651}, issn = {1365-2125}, mesh = {Humans ; Male ; Female ; *Cannabidiol/adverse effects ; *Cannabis/adverse effects ; Post-Acute COVID-19 Syndrome ; Feasibility Studies ; *COVID-19 ; *Hallucinogens ; Dronabinol/adverse effects ; }, abstract = {AIMS: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID.

METHODS: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg δ-9-tetrahydrocannabinol/mL) per day orally. Monthly patient-reported outcome measures of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep and oxygen saturation were assessed using wearable technology.

RESULTS: Twelve (1 male, 11 female) individuals diagnosed with long COVID were recruited into the trial. All participants adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of patient-reported outcome measures and daily self-report.

CONCLUSION: The study drug was safe and well-tolerated, demonstrating feasibility of CBD-dominant cannabis-based medicinal products in individuals diagnosed with long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.}, } @article {pmid38104642, year = {2023}, author = {Sanal-Hayes, NEM and Hayes, LD and Mclaughlin, M and Berry, ECJ and Sculthorpe, NF}, title = {Post-Traumatic Stress Disorder and Complex Post-Traumatic Stress Disorder in People with Long COVID, ME/CFS, and Controls.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2023.12.006}, pmid = {38104642}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {BACKGROUND: Prevalences of post-traumatic stress disorder (PTSD) and complex post-traumatic stress disorder (CPTSD) have not previously been compared between individuals with long coronavirus disease (COVID) and individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and healthy age-matched controls. For these reasons, this study aimed to determine the prevalence of PTSD and CPTSD in individuals with long COVID (n = 21) and ME/CFS (n = 20) and age-matched controls (n = 20).

METHODS: A case-case-control approach was employed; participants completed the International Trauma Questionnaire, a self-report measure of the International Classification of Diseases of PTSD and CPTSD consisting of 18 items. Scores were calculated for each PTSD and Disturbances in Self-Organization (DSO) symptom cluster and summed to produce PTSD and DSO scores. PTSD was diagnosed if the criteria for PTSD were met but not DSO, and CPTSD was diagnosed if the criteria for PTSD and DSO were met. Moreover, each cluster of PTSD and DSO were compared among individuals with long COVID, ME/CFS, and healthy controls.

RESULTS: Individuals with long COVID (PTSD = 5%, CPTSD = 33%) had more prevalence of PTSD and CPTSD than individuals with ME/CFS (PTSD = 0%, CPTSD = 20%) and healthy controls (PTSD = 0%, CPTSD = 0%). PTSD and CPTSD prevalence was greater in individuals with long COVID and ME/CFS than controls. Individuals with long COVID had greater values controls for all PTSD values. Moreover, individuals with long COVID had greater values than controls for all DSO values. Individuals with ME/CFS had greater values than controls for all DSO values. Both long COVID and ME/CFS groups differed in overall symptom scores compared with controls.

CONCLUSION: Findings of this study demonstrated that individuals with long COVID generally had more cases of PTSD and CPTSD than individuals with ME/CFS and healthy controls.}, } @article {pmid38104129, year = {2023}, author = {Chen, J and Chen, J and Lei, Z and Zhang, F and Zeng, LH and Wu, X and Li, S and Tan, J}, title = {Amyloid precursor protein facilitates SARS-CoV-2 virus entry into cells and enhances amyloid-β-associated pathology in APP/PS1 mouse model of Alzheimer's disease.}, journal = {Translational psychiatry}, volume = {13}, number = {1}, pages = {396}, pmid = {38104129}, issn = {2158-3188}, mesh = {Animals ; Humans ; Mice ; *Alzheimer Disease/complications/virology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Chlorocebus aethiops ; *COVID-19/complications ; Disease Models, Animal ; HEK293 Cells ; Mice, Transgenic ; Post-Acute COVID-19 Syndrome ; Presenilin-1 ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus ; Vero Cells ; *Virus Internalization ; }, abstract = {Although there are indications of a trend towards less severe acute respiratory symptoms and a decline in overall lethality from the novel Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), more and more attention has been paid to the long COVID, including the increased risk of Alzheimer's disease (AD) in COVID-19 patients. In this study, we aim to investigate the involvement of N-terminal amyloid precursor protein (APP) in SARS-CoV-2-induced amyloid-β (Aβ) pathology. Utilizing both in vitro and in vivo methodologies, we first investigated the interaction between the spike protein of SARS-CoV-2 and N-terminal APP via LSPR and CoIP assays. The in vitro impacts of APP overexpression on virus infection were further evaluated in HEK293T/ACE2 cells, SH-SY5Y cells, and Vero cells. We also analyzed the pseudovirus infection in vivo in a mouse model overexpressing human wild-type APP. Finally, we evaluated the impact of APP on pseudovirus infection within human brain organoids and assessed the chronic effects of pseudovirus infection on Aβ levels. We reported here for the first time that APP, the precursor of the Aβ of AD, interacts with the Spike protein of SARS-CoV-2. Moreover, both in vivo and in vitro data further indicated that APP promotes the cellular entry of the virus, and exacerbates Aβ-associated pathology in the APP/PS1 mouse model of AD, which can be ameliorated by N-terminal APP blockage. Our findings provide experimental evidence to interpret APP-related mechanisms underlying AD-like neuropathology in COVID-19 patients and may pave the way to help inform risk management and therapeutic strategies against diseases accordingly.}, } @article {pmid38103867, year = {2024}, author = {Kutsuna, S and Onozuka, D and Asano, K and Matsunami, K and Matsuoka, T}, title = {Cross-sectional surveillance study of long COVID in Toyonaka city, Osaka prefecture, Japan.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {30}, number = {6}, pages = {511-515}, doi = {10.1016/j.jiac.2023.12.006}, pmid = {38103867}, issn = {1437-7780}, mesh = {*COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome ; Japan/epidemiology ; Cross-Sectional Studies ; SARS-CoV-2 ; East Asian People ; Humans ; }, abstract = {BACKGROUND: As the COVID-19 epidemic continues, concerns about long-term health impacts, specifically long COVID, persist. While the prevalence and symptomatology of long COVID have been explored in various global contexts, large-scale cohort studies in Japan remain limited, especially after the advent of the Omicron variant.

METHODS: In this observational study, 4,047 residents with a history of COVID-19 living in Toyonaka City, Osaka Prefecture, were assessed for long COVID symptoms using the VOICE mobile application and a paper survey. Respondents provided demographic and health information, as well as information regarding COVID-19 infection and subsequent symptoms. A Cox proportional hazard regression model was used to estimate the multivariable-adjusted hazard ratios and 95 % confidence intervals for overall morbidity of long COVID symptoms.

RESULTS: The survey found that 5.2 % of participants reported the persistence of one or more symptoms at 30 days post-onset. Fatigue was the most commonly reported symptom (1.75 %), followed by hair loss (1.41 %), and cough (1.28 %). Factors associated with an increased risk of experiencing long COVID symptoms included BMI, severe illness during the acute phase, and infection with certain COVID-19 variant strains, including Alpha, Delta, and Omicron. However, the incidence rate of long COVID appears to be decreasing with the dominance of the Omicron variant.

CONCLUSIONS: This large-scale study from Toyonaka City suggests a 5.2 % prevalence rate for persistent COVID-19 symptoms 4 weeks post-infection, potentially indicating a lower prevalence of long COVID in Japanese populations after the rise of the Omicron variant.}, } @article {pmid38103017, year = {2023}, author = {Li, Y and Yamamoto, S and Horii, K and Mizoue, T and Konishi, M and Sugiyama, H and Sugiura, W and Ohmagari, N}, title = {Long COVID during the Omicron predominant waves among Japanese healthcare workers.}, journal = {Journal of medical virology}, volume = {95}, number = {12}, pages = {e29322}, doi = {10.1002/jmv.29322}, pmid = {38103017}, issn = {1096-9071}, support = {//National Center for Global Health and Medicine/ ; //Japan Health Research Promotion Bureau/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Japan/epidemiology ; *COVID-19/epidemiology ; }, } @article {pmid38102626, year = {2023}, author = {Ippoliti, L and Coppeta, L and Somma, G and Bizzarro, G and Borelli, F and Crispino, T and Ferrari, C and Iannuzzi, I and Mazza, A and Paolino, A and Magrini, A and Pietroiusti, A}, title = {Pulmonary function assessment after COVID-19 in vaccinated healthcare workers.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {18}, number = {1}, pages = {31}, pmid = {38102626}, issn = {1745-6673}, abstract = {COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.}, } @article {pmid38101833, year = {2023}, author = {Duncan, E and Alexander, L and Cowie, J and Love, A and Morris, JH and Moss, R and Ormerod, J and Preston, J and Shim, J and Stage, E and Tooman, T and Cooper, K}, title = {Investigating Scottish Long COVID community rehabilitation service models from the perspectives of people living with Long COVID and healthcare professionals: a qualitative descriptive study.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e078740}, pmid = {38101833}, issn = {2044-6055}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; State Medicine ; *COVID-19/epidemiology ; Scotland ; Delivery of Health Care ; Qualitative Research ; }, abstract = {OBJECTIVES: This study aimed to explore the perceptions and experiences of barriers and facilitators to accessing Long COVID community rehabilitation.

DESIGN: We used a qualitative descriptive design over two rounds of data collection with three participant groups: (1) people with experience of rehabilitation for Long COVID (PwLC); (2) National Health Service (NHS) staff delivering and/or managing community rehabilitation services (allied health professionals (AHPs)) and (3) NHS staff involved in strategic planning around Long COVID in their health board (Long COVID leads).

SETTING: Four NHS Scotland territorial health boards.

PARTICIPANTS: 51 interviews: eight Long COVID leads (11 interviews); 15 AHPs (25 interviews) and 15 PwLC (15 interviews).

RESULTS: Three key themes were identified: (1) accessing care for PwLC, (2) understanding Long COVID and its management and (3) strengths and limitations of existing Long COVID rehabilitation services.

CONCLUSIONS: Organisational delivery of Long COVID community rehabilitation is complex and presents multiple challenges. In addition, access to Long COVID community rehabilitation can be challenging. When accessed, these services are valued by PwLC but require adequate planning, publicity and resource. The findings presented here can be used by those developing and delivering services for people with Long COVID.}, } @article {pmid38100898, year = {2024}, author = {Freda, MF and Scandurra, C and Auriemma, E and Guarino, A and Lemmo, D and Martino, ML and Nunziata, F and Maldonato, NM and Continisio, GI}, title = {Long-COVID in children: An exploratory case-control study from a bio-psycho-social perspective.}, journal = {Journal of psychosomatic research}, volume = {176}, number = {}, pages = {111564}, doi = {10.1016/j.jpsychores.2023.111564}, pmid = {38100898}, issn = {1879-1360}, mesh = {Child ; Female ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Cross-Sectional Studies ; }, abstract = {OBJECTIVE: This study aimed to determine psychosocial differences between children with Long-COVID Syndrome (LCS) and two control groups (i.e., children who did not have COVID-19 and children who had previously had COVID-19 but did not develop LCS) from a bio-psycho-social and psychosomatic perspective. To classify children in these three groups, we examined the percentage of children meeting criteria for LCS, the type, frequency, perceived severity of symptoms, and their prevalence compared with children who never had SARS-CoV-2 infection.

METHODS: Data were collected from 198 Italian mothers of children aged 4 to 13 years using a cross-sectional web-based case-control survey. Of these, 105 were mothers of children who had contracted SARS-CoV-2 and 94 were mothers of children who had previously had COVID-19. Information was collected on the type and frequency of symptoms commonly referred to as "Long-COVID symptoms" and psychosocial dimensions (i.e., maternal and child health anxiety, COVID-19 anxiety, adjustment, and child deprivation). Descriptive analyses, chi-square tests, Student's T-Test, and analyses of variance were performed.

RESULTS: 29 children (15% of the total sample) developed LCS, mostly in the neurological/neuropsychiatric domain (59%), and of mild intensity. Regarding psychosocial and psychological dimensions, maternal health anxiety, child deprivation, and fear of SARS-CoV-2 infection differed between groups, with the first two dimensions higher in children with LCS than in controls and the latter lower in children with LCS than in controls.

CONCLUSION: This study sheds light on the need of integrating a psychosocial approach into the medical care of children with LCS and their caregivers.}, } @article {pmid38100573, year = {2023}, author = {McCarthy, MW}, title = {Intravenous immunoglobulin as a potential treatment for long COVID.}, journal = {Expert opinion on biological therapy}, volume = {23}, number = {12}, pages = {1211-1217}, doi = {10.1080/14712598.2023.2296569}, pmid = {38100573}, issn = {1744-7682}, mesh = {United States ; Humans ; *Immunoglobulins, Intravenous/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Chronic Disease ; }, abstract = {INTRODUCTION: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health (NIH) opened enrollment for the therapeutic arm of the RECOVER initiative, a prospective, randomized study to evaluate new treatment options for long coronavirus disease 2019 (long COVID).

AREAS COVERED: One of the first drugs to be studied in this nationwide initiative is intravenous immunoglobulin (IVIG), which will be a treatment option for subjects enrolled in RECOVER-AUTO, a randomized trial to investigate therapeutic strategies for autonomic dysfunction related to long COVID.

EXPERT OPINION: IVIG is a mixture of human antibodies (human immunoglobulin) that has been widely used to treat a variety of diseases, including immune thrombocytopenia purpura, Kawasaki disease, chronic inflammatory demyelinating polyneuropathy, and certain infections such as influenza, human immunodeficiency virus, and measles. However, the role of IVIG in the treatment of post-COVID-19 conditions is uncertain. This manuscript examines what is known about IVIG in the treatment of long COVID and explores how this therapeutic agent may be used in the future to address this condition.}, } @article {pmid38099612, year = {2024}, author = {Slankamenac, J and Ranisavljev, M and Todorovic, N and Ostojic, J and Stajer, V and Ostojic, SM}, title = {Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID.}, journal = {Journal of postgraduate medicine}, volume = {70}, number = {2}, pages = {101-104}, pmid = {38099612}, issn = {0972-2823}, mesh = {Humans ; *Creatine/administration & dosage ; *Breathing Exercises/methods ; Double-Blind Method ; *Dietary Supplements ; Male ; *COVID-19/therapy ; Middle Aged ; Female ; SARS-CoV-2 ; Fatigue/therapy ; Adult ; Treatment Outcome ; }, abstract = {Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months. Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study (P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group (P < 0.05). No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05). These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID.}, } @article {pmid38098317, year = {2024}, author = {El-Baky, NA and Amara, AA and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long COVID: III. Persistence of SARS-CoV-2 and its components.}, journal = {Journal of cellular biochemistry}, volume = {125}, number = {1}, pages = {22-44}, doi = {10.1002/jcb.30514}, pmid = {38098317}, issn = {1097-4644}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Intrinsic Factor ; *COVID-19 ; RNA, Viral/genetics ; }, abstract = {Considerable research has been done in investigating SARS-CoV-2 infection, its characteristics, and host immune response. However, debate is still ongoing over the emergence of post-acute sequelae of SARS-CoV-2 infection (PASC). A multitude of long-lasting symptoms have been reported several weeks after the primary acute SARS-CoV-2 infection that resemble several other viral infections. Thousands of research articles have described various post-COVID-19 conditions. Yet, the evidence around these ongoing health problems, the reasons behind them, and their molecular underpinnings are scarce. These persistent symptoms are also known as long COVID-19. The persistence of SARS-CoV-2 and/or its components in host tissues can lead to long COVID. For example, the presence of viral nucleocapsid protein and RNA was detected in the skin, appendix, and breast tissues of some long COVID patients. The persistence of viral RNA was reported in multiple anatomic sites, including non-respiratory tissues such as the adrenal gland, ocular tissue, small intestine, lymph nodes, myocardium, and sciatic nerve. Distinctive viral spike sequence variants were also found in non-respiratory tissues. Interestingly, prolonged detection of viral subgenomic RNA was observed across all tissues, sometimes in multiple tissues of the same patient, which likely reflects recent but defective viral replication. Moreover, the persistence of SARS-CoV-2 RNA was noticed throughout the brain at autopsy, as late as 230 days following symptom onset among unvaccinated patients who died of severe infection. Here, we review the persistence of SARS-CoV-2 and its components as an intrinsic factor behind long COVID. We also highlight the immunological consequences of this viral persistence.}, } @article {pmid38098110, year = {2023}, author = {Rocha, JQS and Caputo, EL and Vieira, YP and Afonso, MDS and Duro, SMS and de Oliveira Saes, M}, title = {Physical activity status prevents symptoms of long covid: Sulcovid-19 survey.}, journal = {BMC sports science, medicine & rehabilitation}, volume = {15}, number = {1}, pages = {170}, pmid = {38098110}, issn = {2052-1847}, support = {21/2551-0000107-0//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; }, abstract = {BACKGROUND: Physical activity is indicated as a treatment for Long COVID, but prevention is unknown. This study aimed to investigate the relationship between physical activity (PA) before and after acute SARS-Cov-2 infection and the presence of Long COVID symptoms in adults.

METHODS: We used data from the Sulcovid-19, a longitudinal study carried out with individuals who were infected by SARS-Cov-2 between December/2020 and March/2021. Participants were asked about 19 symptoms commonly associated with long COVID. Three PA variables were built, as follows: (1) remained inactive; (2) became inactive; (3) remained active.

RESULTS: 2.919 people were interviewed. The prevalence of individuals who had at least one symptom of Long COVID is 48.3% (95%CI 46.5-51.1). Our results showed that 71.8% (95%CI 70.1-73.4) of the individuals remained inactive, 14.9% (95%CI 13.6-16.2) became inactive and 13.3% (95% CI 12.1-14.6) remained active. The likelihood of experiencing long COVID symptoms was reduced in the musculoskeletal (PR 0.70; 95%CI 0.49-0.99), neurological (PR 0.61; 95%CI 0.43-0.88), and respiratory (PR 0.58; 95%CI 0.35-0.96) systems in those who remained active. In addition, the likelihood of experiencing Long COVID symptoms was 7% less in those who remained active.

CONCLUSIONS: Continuous PA practice showed important protection effect for Long COVID symptoms in adults.}, } @article {pmid38097988, year = {2023}, author = {Carrión-Nessi, FS and Ascanio, LC and Pineda-Arapé, AG and Omaña-Ávila, ÓD and Mendoza-Millán, DL and Romero, SR and Almao-Rivero, AB and Camejo-Ávila, NA and Gebran-Chedid, KJ and Rodriguez-Saavedra, CM and Freitas-De Nobrega, DC and Castañeda, SA and Forero-Peña, JL and Delgado-Noguera, LA and Meneses-Ramírez, LK and Cotuá, JC and Rodriguez-Morales, AJ and Forero-Peña, DA and Paniz-Mondolfi, AE}, title = {New daily persistent headache after SARS-CoV-2 infection in Latin America: a cross-sectional study.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {877}, pmid = {38097988}, issn = {1471-2334}, mesh = {Humans ; Female ; Adult ; Adolescent ; Male ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Latin America/epidemiology ; SARS-CoV-2 ; COVID-19 Vaccines ; *Headache Disorders/diagnosis/etiology ; Headache/epidemiology/etiology ; }, abstract = {BACKGROUND: Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes.

METHODS: We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants' responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups. Participant data was summarized by descriptive statistics. Student's t and Mann-Whitney U tests were used according to the distribution of quantitative variables. For categorical variables, Pearson's chi-square and Fisher's exact tests were used according to the size of expected frequencies. Binomial logistic regression using the backward stepwise selection method was performed to identify factors associated with NDPH.

RESULTS: Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the NDPH diagnostic criteria. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH.

CONCLUSION: This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its associated factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.}, } @article {pmid38097574, year = {2023}, author = {Boes, M and Falter-Braun, P}, title = {Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {460}, pmid = {38097574}, issn = {2059-3635}, support = {101003633//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 01EA1803//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Federal Ministry for Education, Science, Research and Technology)/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Chronic Disease ; Immune System ; }, } @article {pmid38097454, year = {2024}, author = {Cao, Z and Yu, R and Yuan, Q and Ji, W and Li, X and Gao, P and Miao, L and Wen, X and Suo, L}, title = {Impact of the COVID-19 pandemic on routine vaccination coverage under varying prevalence Conditions: A cohort study in Beijing, China.}, journal = {Vaccine}, volume = {42}, number = {2}, pages = {213-219}, doi = {10.1016/j.vaccine.2023.12.014}, pmid = {38097454}, issn = {1873-2518}, mesh = {Child ; Humans ; Infant ; *Vaccination Coverage ; Pandemics ; Cohort Studies ; Beijing/epidemiology ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology/prevention & control ; Vaccination ; China/epidemiology ; Immunization Programs ; }, abstract = {BACKGROUND: The COVID-19 pandemic has experienced various phases including outbreaks, a global health crisis, and eventual de-escalation from a public health emergency of international concern, significantly affecting the delivery and utilization of healthcare services. This study aimed to evaluate the impact of the COVID-19 pandemic on the coverage rate of routine immunization in children under varying prevalence conditions.

METHODS: We conducted a retrospective, population-based cohort study in Beijing, China, utilizing stratified random sampling by birthdate to obtain a sample of 29,811 participants. Subjects were categorized into four cohorts based on when they became eligible for vaccination: the Pre-COVID Period cohort, the COVID-19 Low Epidemic Period cohort, the COVID-19 Surging Period cohort, and the COVID-19 Slowing Down Period cohort. A one-month follow-up was conducted. Cox proportional hazards model was employed to examine associations between the COVID-19 epidemic status and timely vaccination.

RESULTS: Participants age-eligible for vaccination during the COVID-19 Low Epidemic Period demonstrated higher rates of timely vaccination (HR 1.18, 95% CI 1.15-1.22) compared to those eligible during the Pre-COVID Period. Conversely, those eligible during the COVID-19 Surging Period displayed lower rates (HR 0.73, 95% CI 0.66-0.82). No significant difference in vaccination timeliness was observed for those eligible during the COVID-19 Slowing Down Period in comparison to the Pre-COVID Period (HR 0.99, 95% CI 0.91-1.09). By the end of May 2023, DTP3 rate among eligible children during the COVID-19 Surging Period had surpassed 90%.

CONCLUSIONS: Significantly declining rates of timely vaccination were observed during the COVID-19 Surging Period, which lasted two months, but not during the nearly three-year-long COVID-19 Low Epidemic Period. An upward trend in vaccination timeliness followed, culminating in a return to baseline levels over the subsequent 3-4 months. Our findings suggested that the pandemic exerted a decreasing and recoverable impact on the coverage rate of routine immunizations in China.}, } @article {pmid38097277, year = {2023}, author = {Schwartz, RA and Suskind, RM}, title = {Post-COVID-19 neuropsychiatric manifestations: a suggested therapeutic approach to 'long COVID' with azithromycin.}, journal = {Epidemiology and infection}, volume = {152}, number = {}, pages = {e34}, pmid = {38097277}, issn = {1469-4409}, mesh = {Humans ; *Azithromycin/therapeutic use ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {The devastating effects of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not end when the acute illness has terminated. A subset of COVID-19 patients may have symptoms that persist for months. This condition has been described as 'long COVID'. From a historical perspective, it has been recognized that serious long-term neurological sequelae have been associated with RNA viruses such as influenza viruses and coronaviruses. A potential intervention for early post-COVID-19 neuropsychiatric impairment may be the commonly employed, readily available, reasonably priced macrolide antibiotic, azithromycin. We have observed a favourable clinical response with azithromycin in three patients with neurological symptoms associated with long COVID-19. We recommend considering formal clinical trials using azithromycin for patients with post-COVID-19 infection neurological changes including 'COVID fog' or the more severe neurological symptoms that may later develop.}, } @article {pmid38096830, year = {2023}, author = {Ramírez-García, SA}, title = {Perspectives on cycle threshold and viral load in SARS-CoV-2 infection, beyond genetic variants and long COVID.}, journal = {Gaceta medica de Mexico}, volume = {159}, number = {5}, pages = {445-446}, doi = {10.24875/GMM.M23000813}, pmid = {38096830}, issn = {0016-3813}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Viral Load ; SARS-CoV-2 ; }, } @article {pmid38096220, year = {2023}, author = {, }, title = {Correction: Prevalence of mental health problems among children with long COVID: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0296160}, pmid = {38096220}, issn = {1932-6203}, abstract = {[This corrects the article DOI: 10.1371/journal.pone.0282538.].}, } @article {pmid38095071, year = {2024}, author = {Zhao, ZW and Chen, Q and Zhang, XT and Luo, YK}, title = {The CONUT score predicts the length of hospital stay and the risk of long COVID.}, journal = {Nutricion hospitalaria}, volume = {41}, number = {1}, pages = {138-144}, doi = {10.20960/nh.04656}, pmid = {38095071}, issn = {1699-5198}, mesh = {Humans ; Prognosis ; *Post-Acute COVID-19 Syndrome ; Length of Stay ; *COVID-19/epidemiology ; SARS-CoV-2 ; Nutritional Status ; Retrospective Studies ; Nutrition Assessment ; }, abstract = {Objective: the Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status of patients. We aimed to investigate the value of CONUT score on predicting length of hospital stay (LOS) and the risk of long COVID in patients with COVID-19. Methods: a total of 151 patients with COVID-19 were enrolled for analysis. Patients were followed up for two years from three months after the onset of SARS-CoV-2 infection. CONUT score was calculated on admission. The correlation between CONUT score and LOS were assessed by Spearman's rank correlation coefficient and multivariate linear analysis. The association between different CONUT grade and long COVID was evaluated by Kaplan-Meier survival curves with log-rank test and Cox proportional hazard models. Results: Spearman's rank correlation coefficient showed that CONUT scores were positively correlated with LOS (r = 0.469, p < 0.001). Multivariate linear analysis showed that CONUT score is the only independent determinant of LOS (B 2.055, 95 % CI: 1.067-3.043, p < 0.001). A total of 53 (35.10 %) patients with long COVID were identified. Kaplan-Meier cumulative survival curves and Cox proportional hazards analyses showed that the incidence of long COVID in patients with a higher CONUT score was significantly higher than in patients with lower CONUT score (p < 0.001). Conclusions: higher CONUT score predicts longer LOS and the risk of long COVID in patients with COVID-19. The CONUT score might be useful for risk stratification in COVID-19 patients and help to develop new nutritional treatment strategies for long COVID.}, } @article {pmid38093341, year = {2023}, author = {Amer, F and López, T and Gil-Conesa, M and Carlos, S and Ariño, AH and Carmona-Torre, F and Martínez-González, MA and Fernandez-Montero, A}, title = {Association between COVID-19 and outstanding academic performance at a Spanish university.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {81}, number = {1}, pages = {213}, pmid = {38093341}, issn = {0778-7367}, support = {0011-3638-2020-000013//Gobierno de Navarra/ ; }, abstract = {BACKGROUND: SARS-CoV-2 is the causative agent of COVID-19 identified in December 2019, an acute infectious respiratory disease that can cause persistent neurological and musculoskeletal symptoms such as headache, fatigue, myalgias difficulty concentrating, among others including acute cerebrovascular disease with a prevalence of 1-35%. The aim of this study is to evaluate the impact of COVID-19 in undergraduate students on their academic performance as an indicator of their intellectual ability and performance in a university that maintained 100% face-to-face teaching during the 2020-2021 academic year.

METHODS: A total of 7,039 undergraduate students were analyzed in a prospective cohort study at the University of Navarra. A questionnaire including sociodemographic and behavioral questions was sent. PCRs were performed throughout the academic year for the diagnosis of SARS-CoV-2 infection and students' academic results were provided by the academic center, adjusted descriptive and multivariate models were performed to assess the association.

RESULTS: A total of 658 (9.3%) participants were diagnosed with COVID-19, almost 4.0% of them achieved outstanding academic results, while uninfected students did so in 7.3%. SARS-CoV-2 infection was associated with a significant decrease in having outstanding academic results (OR = 0.57; 95% CI: 0.38-0.86).

CONCLUSION: Having COVID-19 disease, decreased academic performance in undergraduate students. Therefore, it is necessary to prevent infection even in the youngest sections of the population.}, } @article {pmid38093291, year = {2023}, author = {Cohen, J and van der Meulen Rodgers, Y}, title = {An intersectional analysis of long COVID prevalence.}, journal = {International journal for equity in health}, volume = {22}, number = {1}, pages = {261}, pmid = {38093291}, issn = {1475-9276}, support = {#90RTEM0006-01-00//National Institute on Disability, Independent Living, and Rehabilitation Research/ ; }, mesh = {Adult ; Humans ; Female ; Male ; *Post-Acute COVID-19 Syndrome ; Gender Identity ; Prevalence ; Intersectional Framework ; *COVID-19/epidemiology ; }, abstract = {BACKGROUND: Long COVID symptoms - which include brain fog, depression, and fatigue - are mild at best and debilitating at worst. Some U.S. health surveys have found that women, lower income individuals, and those with less education are overrepresented among adults with long COVID, but these studies do not address intersectionality. To fill this gap, we conduct an intersectional analysis of the prevalence and outcomes of long COVID in the U.S. We posit that disparities in long COVID have less to do with the virus itself and more to do with social determinants of health, especially those associated with occupational segregation and the gendered division of household work.

METHODS: We use 10 rounds of Household Pulse Survey (HPS) data collected between June 2022 and March 2023 to perform an intersectional analysis using a battery of descriptive statistics that evaluate (1) the prevalence of long COVID and (2) the interference of long COVID symptoms with day-to-day activities. We also use the HPS data to estimate a set of multivariate logistic regressions that relate the odds of having long COVID and activity limitations due to long COVID to a set of individual characteristics as well as intersections by sex, race/ethnicity, education, and sexual orientation and gender identity.

RESULTS: Findings indicate that women, some people of color, sexual and gender minorities, and people without college degrees are more likely to have long COVID and to have activity limitations from long COVID. Women have considerably higher odds of developing long COVID compared to men, a disparity exacerbated by having less education. Intersectional analysis by gender, race, ethnicity, and education reveals a striking step-like pattern: college-educated men have the lowest prevalence of long COVID while women without college educations have the highest prevalence. Daily activity limitations are more evenly distributed across demographics, but a different step-like pattern is present: fewer women with degrees have activity limitations while limitations are more widespread among men without degrees. Regression results confirm the negative association of long COVID with being a woman, less educated, Hispanic, and a sexual and gender minority, while results for the intersectional effects are more nuanced.

CONCLUSIONS: Results point to systematic disparities in health, highlighting the urgent need for policies that increase access to quality healthcare, strengthen the social safety net, and reduce economic precarity.}, } @article {pmid38093182, year = {2023}, author = {Massey, D and Saydah, S and Adamson, B and Lincoln, A and Aukerman, DF and Berke, EM and Sikka, R and Krumholz, HM}, title = {Prevalence of covid-19 and long covid in collegiate student athletes from spring 2020 to fall 2021: a retrospective survey.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {876}, pmid = {38093182}, issn = {1471-2334}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Prevalence ; *COVID-19/epidemiology ; SARS-CoV-2 ; Athletes/psychology ; Students ; }, abstract = {BACKGROUND: Symptomatic COVID-19 and Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 (PASC) or post-COVID conditions, have been widely reported in young, healthy people, but their prevalence has not yet been determined in student athletes. We sought to estimate the prevalence of reported COVID-19, symptomatic COVID-19, and Long COVID in college athletes in the United States attending 18 schools from spring 2020 to fall 2021.

METHODS: We developed an online survey to measure the prevalence of student athletes who tested positive for COVID-19, developed Long COVID, and did not return to their sport during the relevant time period. We surveyed a convenience sample of 18 collegiate school administrators, representing about 7,000 student athletes. Of those schools surveyed, 16 responded regarding the spring 2020 semester, and 18 responded regarding the full academic year of fall 2020 to spring 2021 (both semesters).

RESULTS: According to the survey responses, there were 9.8% of student athletes who tested positive for COVID-19 in spring 2020 and 25.4% who tested positive in the academic year of fall 2020 to spring 2021. About 4% of student athletes who tested positive from spring 2020 to spring 2021 developed Long COVID, defined as new, recurring, or ongoing physical or mental health consequences occurring 4 or more weeks after SARS-CoV-2 infection.

CONCLUSIONS: This study highlights that Long COVID occurs among young, healthy athletes and is a real consequence of COVID-19. Understanding the prevalence of Long COVID in this population requires longer follow-up and further study.}, } @article {pmid38093111, year = {2023}, author = {O'Leary, K}, title = {Seeing through the fog of long COVID.}, journal = {Nature medicine}, volume = {29}, number = {12}, pages = {2973}, doi = {10.1038/s41591-023-02713-w}, pmid = {38093111}, issn = {1546-170X}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Deep Brain Stimulation ; Time Factors ; }, } @article {pmid38091027, year = {2024}, author = {Rana, P and Patial, S and Soni, V and Singh, P and Khosla, A and Thakur, S and Hussaisn, CM and de Carvalho Nagliate, P and Meili, L and Selvasembian, R and Raizada, P}, title = {"Long COVID" and Its Impact on The Environment: Emerging Concerns and Perspectives.}, journal = {Environmental management}, volume = {73}, number = {3}, pages = {471-480}, pmid = {38091027}, issn = {1432-1009}, mesh = {Humans ; *Air Pollution/analysis ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has caused unprecedented global health and economic crises. The emergence of long COVID-19 has raised concerns about the interplay between SARS-CoV-2 infections, climate change, and the environment. In this context, a concise analysis of the potential long-term effects of the COVID-19 epidemic along with the awareness aboutenvironmental issues are realized. While COVID-19 effects in the short-term have reduced environmental air pollutants and pressures, CO2 emissions are projected to increase as the economy recovers and growth rates return to pre-COVID-19 levels. This review discusses the systematic effects of both the short-term and long-term effects of the pandemic on the clean energy revolution and environmental issues. This article also discusses opportunities to achieve long-term environmental benefits and emphasizes the importance of future policies in promoting global environmental sustainability. Future directions for growth and recovery are presented to cope with long COVID-19 epidemic along with the critical findings focussing on various aspects: waste management, air quality improvement.}, } @article {pmid38090997, year = {2024}, author = {Suran, M}, title = {Studies Investigate Whether Antivirals Like Paxlovid May Prevent Long COVID.}, journal = {JAMA}, volume = {331}, number = {2}, pages = {98-100}, doi = {10.1001/jama.2023.24103}, pmid = {38090997}, issn = {1538-3598}, mesh = {Humans ; *Antiviral Agents/therapeutic use ; COVID-19/complications ; *Post-Acute COVID-19 Syndrome/prevention & control ; Ritonavir/therapeutic use ; }, } @article {pmid38090994, year = {2024}, author = {Harris, E}, title = {Long COVID in Nursing Home Residents Manifests as Functional Decline.}, journal = {JAMA}, volume = {331}, number = {1}, pages = {15}, doi = {10.1001/jama.2023.24682}, pmid = {38090994}, issn = {1538-3598}, mesh = {Humans ; *Activities of Daily Living ; *Nursing Homes ; *Post-Acute COVID-19 Syndrome/complications/psychology ; *Functional Status ; }, } @article {pmid38090572, year = {2023}, author = {Gu, J and Liu, Q and Zhang, J and Xu, S}, title = {COVID-19 and trained immunity: the inflammatory burden of long covid.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1294959}, pmid = {38090572}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Trained Immunity ; Interleukin-6 ; *COVID-19 ; Inflammation ; }, abstract = {Severe COVID-19 elicits excessive inflammation mediated by innate immune cells like monocytes. Recent evidence reveals extensive epigenetic changes in monocytes during recovery from severe COVID-19, including increased chromatin accessibility at genes related to cytokine production and leukocyte activation. These changes likely originate from the reprogramming of upstream hematopoietic stem and progenitor cells (HSPCs) and represent "trained immunity". HSPC-to-monocyte transmission of epigenetic memory may explain the persistence of these monocyte alterations despite their short lifespan. IL-6 appears pivotal for imprinting durable epigenetic modifications in monocytes during acute infection, with IL-1β potentially playing a contributory role. The poised inflammatory phenotype of monocytes post-COVID-19 may drive chronic inflammation and tissue damage, contributing to post-acute sequelae of COVID-19 symptoms. COVID-19 could also exacerbate inflammation-related diseases, such multisystem inflammatory syndromes, by altering innate immune tendencies via hematopoietic epigenetic reprogramming. Further clinical investigations quantifying inflammatory mediators and mapping epigenetic changes in HSPCs/monocytes of recovering patients are warranted. Research should also examine whether COVID-19 elicits transgenerational inheritance of epigenetic alterations. Elucidating mechanisms underlying COVID-19-induced monocyte reprogramming and developing interventions targeting key inflammatory regulators like IL-6 may mitigate the sustained inflammatory burden imposed by the aberrant trained immunity post-COVID-19.}, } @article {pmid38089028, year = {2023}, author = {Straßburger, C and Hieber, D and Karthan, M and Jüster, M and Schobel, J}, title = {Return to work after Post-COVID: describing affected employees' perceptions of personal resources, organizational offerings and care pathways.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1282507}, pmid = {38089028}, issn = {2296-2565}, mesh = {Humans ; *COVID-19 ; Critical Pathways ; *Return to Work ; SARS-CoV-2 ; Workplace ; }, abstract = {BACKGROUND: Most individuals recover from the acute phase of infection with the SARS-CoV-2 virus, however, some encounter prolonged effects, referred to as the Post-COVID syndrome. Evidence exists that such persistent symptoms can significantly impact patients' ability to return to work. This paper gives a comprehensive overview of different care pathways and resources, both personal and external, that aim to support Post-COVID patients during their work-life reintegration process. By describing the current situation of Post-COVID patients pertaining their transition back to the workplace, this paper provides valuable insights into their needs.

METHODS: A quantitative research design was applied using an online questionnaire as an instrument. Participants were recruited via Post-COVID outpatients, rehab facilities, general practitioners, support groups, and other healthcare facilities.

RESULTS: The analyses of 184 data sets of Post-COVID affected produced three key findings: (1) The evaluation of different types of personal resources that may lead to a successful return to work found that particularly the individuals' ability to cope with their situation (measured with the FERUS questionnaire), produced significant differences between participants that had returned to work and those that had not been able to return so far (F = 4.913, p = 0.001). (2) In terms of organizational provisions to facilitate successful reintegration into work-life, predominantly structural changes (i.e., modification of the workplace, working hours, and task) were rated as helpful or very helpful on average (meanworkplace 2.55/SD = 0.83, meanworking hours 2.44/SD = 0.80; meantasks 2.55/SD = 0.83), while the remaining offerings (i.e., job coaching or health courses) were rated as less helpful or not helpful at all. (3) No significant correlation was found between different care pathways and a successful return to work.

CONCLUSION: The results of the in-depth descriptive analysis allows to suggests that the level of ability to cope with the Post-COVID syndrome and its associated complaints, as well as the structural adaptation of the workplace to meet the needs and demands of patients better, might be important determinants of a successful return. While the latter might be addressed by employers directly, it might be helpful to integrate training on coping behavior early in care pathways and treatment plans for Post-COVID patients to strengthen their coping abilities aiming to support their successful return to work at an early stage.}, } @article {pmid38088735, year = {2023}, author = {Feter, N and Caputo, EL and Leite, JS and Delpino, FM and Silva, LSD and Vieira, YP and Paz, IA and Rocha, JQS and Silva, CND and Schröeder, N and Silva, MCD and Rombaldi, AJ}, title = {Prevalence and factors associated with long COVID in adults from Southern Brazil: findings from the PAMPA cohort.}, journal = {Cadernos de saude publica}, volume = {39}, number = {12}, pages = {e00098023}, pmid = {38088735}, issn = {1678-4464}, mesh = {Adult ; Male ; Humans ; Female ; Child ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Brazil/epidemiology ; Pandemics ; Prevalence ; SARS-CoV-2 ; }, abstract = {Most COVID-19 survivors have reported experiencing persistent symptoms after the infection - these types of cases are known as long COVID. Since Brazil was an epicenter of the COVID-19 pandemic, a high burden of long COVID is expected. This study aimed to identify the prevalence and factors associated with long COVID in adults in Southern Brazil, analyzing data from the PAMPA cohort. Participants filled out a self-reported online questionnaire in June 2022. This study only included subjects who tested positive for COVID-19. Long COVID was defined by any symptoms that persisted for at least three months after the SARS-CoV-2 infection. Poisson's regression models with robust variance were used to identify factors associated with long COVID; and results were reported as prevalence ratios (PR) and respective 95% confidence intervals (95%CI). A total of 1,001 participants (77.4% women, mean age [SD] = 38.3 [11.9] years) were analyzed. The prevalence of long COVID among these patients was 77.4% (95%CI: 74.7; 79.9). The likelihood of long COVID was higher in unvaccinated participants (PR = 1.23, 95%CI: 1.06; 1.42), in those with chronic conditions (PR = 1.13, 95%CI: 1.04; 1.24), and in those who were hospitalized due to the COVID-19 infection (PR = 1.24, 95%CI: 1.16; 1.32). This prevalence was also higher in women (PR = 1.21, 95%CI: 1.09; 1.33) than in men. Physical activity was associated with a reduced likelihood of fatigue, neurological complications, coughing, and headaches as persistent symptoms after a COVID-19 infection. It was found that three out of four adults in Southern Brazil experienced long COVID. Public policies aiming to reduce the burden of long COVID must be prioritized, especially in groups that are at higher risk of developing this harmful condition.}, } @article {pmid38088242, year = {2024}, author = {Bonora, BM and Marassi, M and Fogar, P and Zuin, J and Cappellari, R and Marinello, S and Ferrari, A and Cattelan, A and Avogaro, A and Basso, D and Fadini, GP}, title = {Circulating haematopoietic stem cells and long-term outcomes of COVID-19.}, journal = {European journal of clinical investigation}, volume = {54}, number = {4}, pages = {e14150}, doi = {10.1111/eci.14150}, pmid = {38088242}, issn = {1365-2362}, support = {//Fondazione Cassa di Risparmio di Padova e Rovigo/ ; 202077EYN7//Italian Ministry of Education University and Research/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Serotherapy ; Hospitalization ; Hematopoietic Stem Cells ; *Diabetes Mellitus/epidemiology ; }, abstract = {BACKGROUND AND AIMS: An acute depletion of circulating haematopoietic stem/progenitor cells (HSPCs) occurs during COVID-19, especially among patients with a poorer disease course. We herein examined whether HSPCs levels at hospital admission for COVID-19 predict 1-year mortality and the long-COVID syndrome.

MATERIALS AND METHODS: Patients hospitalized for COVID-19 in an infectious disease ward were consecutively enrolled. Circulating HSPC levels were assessed by flow cytometry as cells expressing CD34 and/or CD133. Follow-up was performed for 12 months after hospitalization through the review of electronic medical records and demographic local registers.

RESULTS: The study included 100 patients, 36 of whom reported symptoms of long-COVID and 20 died during follow-up. The reduction of 1-SD of HSPCs was associated with a 3- to 5-fold increase in the risk of 1-year mortality. Age, admission hyperglycaemia, C-reactive protein peak, liver enzymes, the need of high-flow oxygen and/or invasive ventilation were predictors of mortality at univariate analysis. Among pre-existing comorbidities, coronary heart disease and chronic kidney disease, but not diabetes, were associated with 1-year mortality. In multivariate analyses, HSPCs remained significantly associated with 1-year mortality independently of confounders. The development of pneumonia an in-hospital treatment with glucocorticoids and convalescent plasma were associated with long-COVID symptoms at follow-up. HSPCs, diabetes and other comorbidities were not predictors of long-COVID.

CONCLUSIONS: In a cohort of patients hospitalized for COVID-19, lower HSPC levels at the time of admission were independent predictors of 1-year mortality. However, COVID-19 severity, but not HSPC level, was significantly associated with the development of long-COVID symptoms.}, } @article {pmid38088231, year = {2024}, author = {Sansone, F and Di Filippo, P and Russo, D and Sgrazzutti, L and Di Pillo, S and Chiarelli, F and Attanasi, M}, title = {Lung function assessment in children with Long-Covid syndrome.}, journal = {Pediatric pulmonology}, volume = {59}, number = {2}, pages = {472-481}, doi = {10.1002/ppul.26779}, pmid = {38088231}, issn = {1099-0496}, support = {//None/ ; }, mesh = {Child ; Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Lung/diagnostic imaging ; }, abstract = {INTRODUCTION: A significant percentage of patients who survived the Coronavirus Infection Disease 2019 (COVID-19) showed persistent general and respiratory symptoms even months after recovery. This condition, called Post-Acute Sequelae of COVID-19 or Long-Covid syndrome (LCS), has been described also in children with positive history for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Little is known about the pathophysiologic mechanisms underlying this syndrome. The aim of this study was to investigate any difference between children with LCS and asymptomatic peers with previous COVID-19 in terms of lung function and lung ultrasound (LUS) patterns. Secondly, we tested associations between lung function abnormalities and LUS findings with Long-Covid.

METHODS: We carried out a prospective, descriptive, observational study including 58 children aged 5-17 years: 28 with LCS compared to 30 asymptomatic children with previous COVID-19. We collected demographic data, history of asthma, allergy or smoke exposure, and acute COVID-19 symptoms. After a median period of 4.5 months (1%-95% range 2-21) since the infection, lung function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide (DLCO). Airways inflammation was investigated by fractional exhaled nitric oxide (FeNO). LUS was performed independently by two experienced clinicians.

RESULTS: We found that children with LCS were older than controls (mean (SD) 12 (4.1) vs. 9.7 (2.6); p = .04). Children with LCS complained more frequently fatigue (46.4%), cough (17.9%), exercise intolerance (14.3%) and dyspnea (14.3%). Lung function was normal and similar between the two groups. The frequency of LUS abnormalities was similar between the two groups (43.3% children with LCS vs. 56.7% controls; p = .436). Children with LCS showed lower FeNO values (log difference -0.30 (CI 95% -0.50, -0.10)), but no association of LCS with a lower lung function and abnormal LUS findings was found.

CONCLUSIONS: LCS seems to be more frequent in older age children. Lung functional and structural abnormalities were not different between children with LCS and asymptomatic subjects with previous COVID-19. In addition, children with LCS showed lower FeNO values than controls, suggesting its potential role as a marker in LCS. However, further and larger studies are needed to confirm our findings.}, } @article {pmid38088068, year = {2023}, author = {Tebeka, S and Carcaillon-Bentata, L and Decio, V and Alleaume, C and Beltzer, N and Gallay, A and Lemogne, C and Pignon, B and Makovski, TT and Coste, J}, title = {Complex association between post-COVID-19 condition and anxiety and depression symptoms.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {67}, number = {1}, pages = {e1}, pmid = {38088068}, issn = {1778-3585}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Depression/epidemiology/diagnosis ; SARS-CoV-2 ; Anxiety/epidemiology/diagnosis ; Anxiety Disorders/epidemiology ; }, abstract = {BACKGROUND: To assess the associations between anxiety and depressive symptoms and post-COVID-19 condition (PCC) by exploring the direction of these associations and their relevance in the definition of PCC.

METHODS: Nationwide survey among French adults, recruited between March and April, 2022, using a quota method to capture a representative sample of the general population with regard to sex, age, socioeconomic status, size of the place of residence, and region. We included all participants who met the World Health Organization (WHO) definition of PCC in addition to a random sample of participants infected with SARS-COV-2 for at least 3 months but without PCC. Self-reported anxiety and depressive symptoms, chronic anxiety and depression (for more than 3 years), and anxiety and depression were measured using the GAD-2 and PHQ-2 questionnaires, respectively.

RESULTS: In a sample of 1,095 participants with PCC and 1,021 participants infected with SARS-COV-2 without PCC, 21% had self-reported anxiety and 18% self-reported depression, whereas 33% and 20% had current measured symptoms of anxiety and depression, respectively. The high prevalence of these symptoms cannot only be explained by the characterization of PCC, as only 13.4% of anxiety symptoms and 7.6% of depressive symptoms met the WHO criteria for PCC. Only one participant met the WHO criteria based on self-reported anxiety or depressive symptoms alone, as these were always combined with other symptoms in patients with PCC. Chronic symptoms were associated with PCC (aOR 1.27; 95% CI: 1.00-1.61). In addition, measured anxiety was associated with PCC (aOR = 1.29; 95% CI: 1.02-1.62).

CONCLUSIONS: Pre-COVID-19 chronic anxiety and depression may play a role in the development of PCC or share vulnerability factors with it. Our results challenge the inclusion of anxiety and depression in the definition of PCC.}, } @article {pmid38087445, year = {2024}, author = {Levin, A}, title = {Predicting Outcomes in Nephrology: Lots of Tools, Limited Uptake: How Do We Move Forward?.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {35}, number = {3}, pages = {361-363}, pmid = {38087445}, issn = {1533-3450}, mesh = {*Nephrology ; Biological Transport ; }, } @article {pmid38087299, year = {2023}, author = {Brehon, K and Miciak, M and Hung, P and Chen, SP and Perreault, K and Hudon, A and Wieler, M and Hunter, S and Hoddinott, L and Hall, M and Churchill, K and Brown, DA and Brown, CA and Bostick, G and Skolnik, K and Lam, G and Weatherald, J and Gross, DP}, title = {"None of us are lying": an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {1396}, pmid = {38087299}, issn = {1472-6963}, support = {466857/CAPMC/CIHR/Canada ; 466857/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Qualitative Research ; *COVID-19/epidemiology ; Health Services ; Delivery of Health Care ; Health Services Accessibility ; }, abstract = {BACKGROUND: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs.

METHODS: Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed.

RESULTS: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants.

CONCLUSION: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.}, } @article {pmid38086949, year = {2023}, author = {Peppercorn, K and Edgar, CD and Kleffmann, T and Tate, WP}, title = {A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22068}, pmid = {38086949}, issn = {2045-2322}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Leukocytes, Mononuclear/metabolism ; Proteome/metabolism ; Post-Acute COVID-19 Syndrome ; Pilot Projects ; SARS-CoV-2 ; *COVID-19/metabolism ; *Virus Diseases/metabolism ; }, abstract = {Of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ~ 10% develop the chronic post-viral debilitating condition, long COVID (LC). Although LC is a heterogeneous condition, about half of cases have typical post-viral fatigue with onset and symptoms that are very similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A key question is whether these conditions are closely related. ME/CFS is a post-stressor fatigue condition that arises from multiple triggers. To investigate the pathophysiology of LC, a pilot study of patients (n = 6) and healthy controls (n = 5) has used quantitative proteomics to discover changes in peripheral blood mononuclear cell (PBMC) proteins. A principal component analysis separated all long COVID patients from healthy controls. Analysis of 3131 proteins identified 162 proteins differentially regulated, of which 37 were related to immune functions, and 21 to mitochondrial functions. Markov cluster analysis identified clusters involved in immune system processes, and two aspects of gene expression-spliceosome and transcription. These results were compared with an earlier dataset of 346 differentially regulated proteins in PBMC's from ME/CFS patients (n = 9) analysed by the same methodology. There were overlapping protein clusters and enriched molecular pathways particularly in immune functions, suggesting the two conditions have similar immune pathophysiology as a prominent feature, and mitochondrial functions involved in energy production were affected in both conditions.}, } @article {pmid38085610, year = {2024}, author = {Chen, Z and Pollack, CV and Rodriguez, R}, title = {A practice-based approach to emergency department evaluation and management of patients with postacute sequelae after COVID-19 infection: long COVID.}, journal = {Emergency medicine practice}, volume = {26}, number = {1}, pages = {1-28}, pmid = {38085610}, issn = {1559-3908}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; Patients ; Disease Progression ; Emergency Service, Hospital ; }, abstract = {Afflicting millions of people across the world, "long COVID" is a new disease entity that can present with a diverse array of symptoms of variable severity, affecting nearly every organ system. The presumptive diagnosis of long COVID is largely clinical, and should be made only after other serious etiologies have been excluded. Workup is driven by the patient's presenting acute symptoms, comorbidities, and physical examination findings. This issue reviews the research and current evidence on the etiology of COVID-19 infection and long COVID and presents a practice-based approach to the management of patients presenting with its postacute sequelae.}, } @article {pmid38083997, year = {2024}, author = {Collins, E and Philippe, E and Gravel, CA and Hawken, S and Langlois, MA and Little, J}, title = {Serological markers and long COVID-A rapid systematic review.}, journal = {European journal of clinical investigation}, volume = {54}, number = {4}, pages = {e14149}, doi = {10.1111/eci.14149}, pmid = {38083997}, issn = {1365-2362}, support = {//CIHR/ ; }, mesh = {Humans ; *COVID-19/immunology/blood ; *Immunoglobulin G/blood/immunology ; *Biomarkers/blood ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Antibodies, Viral/blood ; Spike Glycoprotein, Coronavirus/immunology ; }, abstract = {BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights.

METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s).

RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.

CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.}, } @article {pmid38083801, year = {2024}, author = {Bonner, C and Ghouralal, SL}, title = {Long COVID and Chronic Conditions in the US Workforce: Prevalence, Productivity Loss, and Disability.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {3}, pages = {e80-e86}, doi = {10.1097/JOM.0000000000003026}, pmid = {38083801}, issn = {1536-5948}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology ; *Musculoskeletal Diseases/epidemiology ; Workforce ; }, abstract = {OBJECTIVE: This study examines how long COVID, chronic conditions, and work outcomes affect the general workforce.

METHODS: It examines the prevalence of long COVID and its associations with chronic conditions, and other sociodemographic characteristics using 2022 National Health Interview Survey data.

RESULTS: Long COVID affected work attendance and disability risk, especially in those with mental health issues, angina, stroke, cancer, diabetes, chronic lung conditions, and musculoskeletal conditions.

CONCLUSION: This study reveals the relationships between long COVID, chronic conditions, and work outcomes.}, } @article {pmid38081885, year = {2023}, author = {Aziz, R and Siles, N and Kelley, M and Wylie, D and Melamed, E and Brode, WM}, title = {Clinical characteristics of Long COVID patients presenting to a dedicated academic post-COVID-19 clinic in Central Texas.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21971}, pmid = {38081885}, issn = {2045-2322}, mesh = {Humans ; Female ; Adult ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Retrospective Studies ; Texas/epidemiology ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Post-acute sequelae SARS-CoV-2 (PASC), also known as Long COVID, is a complex and widely recognized illness with estimates ranging from 5 to 30% of all COVID-19 cases. We performed a retrospective chart review of patients who presented to a dedicated Post-COVID-19 clinic between June 2021 and May 2022. The median patient age was 44.5 years, 63.5% patients were female, and patients presented at a median of 10.4 months from acute COVD-19 infection. 78% self-identified their race as white, and 21% identified as Latino ethnicity. During the acute COVID-19 infection, 50% of patients experienced moderate disease severity and 10.5% were hospitalized. The top three co-morbid conditions prior to SARS-CoV-2 infection included mental health conditions, hypertension and asthma. Patients reported a median of 18 new symptoms following COVID-19 illness, the most common were fatigue (89%), forgetfulness or "brain fog" (89%), and difficulty concentrating (77%). MoCA (Montreal Cognitive Assessment) assessment demonstrated that 46% had mild cognitive dysfunction. PHQ-9 (Patient Health Questionnaire) testing revealed 42% had moderate to severe depression, and 38% had moderate to severe anxiety on the GAD-7 (Generalized Anxiety Disorder) assessment. Symptom burden was similar across gender, age, and initial disease severity. PASC patients presenting to an academic Post-COVID-19 clinic experienced numerous multisystem symptoms and functional impairment, independent of the initial COVID-19 disease severity.}, } @article {pmid38078542, year = {2024}, author = {Vandersmissen, G and Verbeeck, J and Henckens, P and Van Dyck, J and Wuytens, C and Molenberghs, G and Godderis, L}, title = {Sick leave due to SARS-CoV-2 infection.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {7}, pages = {486-492}, doi = {10.1093/occmed/kqad140}, pmid = {38078542}, issn = {1471-8405}, mesh = {Humans ; *Sick Leave/statistics & numerical data ; *COVID-19/epidemiology ; Male ; Female ; Adult ; Belgium/epidemiology ; Middle Aged ; *SARS-CoV-2 ; *Absenteeism ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) caused a high burden of sick leave worldwide. Long-term sick leave for COVID-19 may be longer than for other influenza-like syndromes. The real impact of long COVID on absenteeism remains uncertain.

AIMS: To investigate the burden of sick leave, especially >12 weeks, in Belgian workers with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from July 2020 to September 2021 and to compare these figures with sick leave for other infectious diseases.

METHODS: We coupled a database of SARS-CoV-2-positive workers and workers who were absent for other infections with objective absence data. Predictors of prolonged sickness were evaluated by negative binomial regression, Cox proportional hazards regression and ordinal logistic regression.

RESULTS: The study population involved 2569 workers who tested positive for SARS-CoV-2 and 392 workers who were absent for other infectious diseases. In total, 16% (95% CI 14-17%) of workers with a positive SARS-CoV-2 test had no sick leave registered. Fourteen out of 1000 (95% CI 9-20‰) workers with absenteeism for COVID-19 experienced sick leave >12 weeks as compared to 43 out of 1000 workers (95% CI 3-69‰) with absenteeism due to other infections. When including PCR-positive workers without sick leave, the prevalence of long-term sick leave decreased to 12 per 1000 (95% CI8-17‰). Long-term sick leave was associated with older age, high previous sick leave and low educational level.

CONCLUSIONS: The prevalence of long-term sick leave was lower than estimated in earlier investigations regardless of worrying reports about post-COVID-19 syndrome.}, } @article {pmid38078498, year = {2024}, author = {Bland, D and Evans, R and Binesmael, A and Wood, S and Qureshi, SP and Fearnley, K and Small, A and Strain, WD and Agius, R}, title = {Post-acute COVID-19 complications in UK doctors: results of a cross-sectional survey.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {99-103}, doi = {10.1093/occmed/kqad120}, pmid = {38078498}, issn = {1471-8405}, support = {//NIHR Exeter Clinical Research Facility/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *Physicians ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: As a consequence of their occupation, doctors and other healthcare workers were at higher risk of contracting coronavirus disease 2019 (COVID-19), and more likely to experience severe disease compared to the general population. However, systematic information on post-acute COVID complications in doctors is very limited.

AIMS: This study aimed to determine the symptoms, perceived determinants, health and occupational impact, and consequent needs relating to post-acute COVID complications in UK doctors.

METHODS: An online cross-sectional survey was distributed to UK doctors self-identifying as having Long COVID or other post-acute COVID complications.

RESULTS: Of 795 responses, 603 fulfilled the inclusion criteria of being a UK-based medical doctor experiencing one or more post-acute COVID complications. Twenty-eight per cent reported a lack of adequate Respiratory Protective Equipment at the time of contracting COVID-19. Eighteen per cent of eligible respondents reported that they had been unable to return to work since acquiring COVID.

CONCLUSIONS: Post-acute COVID (Long COVID) in UK doctors is a substantial burden for respondents to our questionnaire. The results indicated that insufficient respiratory protection could have contributed to occupational disease, with COVID-19 being contracted in the workplace, and resultant post-COVID complications. Although it may be too late to address the perceived determinants of inadequate protection for those already suffering with Long COVID, more investment is needed in rehabilitation and support of those afflicted.}, } @article {pmid38077784, year = {2023}, author = {Lyons, CE and Zhu, I and Gill, MK}, title = {Accelerated progression of diabetic retinopathy following severe COVID-19 infection.}, journal = {American journal of ophthalmology case reports}, volume = {32}, number = {}, pages = {101911}, pmid = {38077784}, issn = {2451-9936}, abstract = {PURPOSE: The impact of SARS-CoV-2 infection on pre-existing retinal pathology is currently unknown.

OBSERVATIONS: We present a unique case of rapidly progressing diabetic retinopathy (DR) following severe COVID-19 infection requiring supplemental oxygen and subsequent long-COVID.

CONCLUSIONS AND IMPORTANCE: Following infection with SARS-CoV-2, the associated acute and possible long-term hypoxia has the potential to affect the retina and accelerate the natural course of diabetic retinopathy.}, } @article {pmid38075959, year = {2023}, author = {Honchar, O and Ashcheulova, T}, title = {Short-term echocardiographic follow-up after hospitalization for COVID-19: a focus on early post-acute changes.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1250656}, pmid = {38075959}, issn = {2297-055X}, abstract = {BACKGROUND: Impaired physical functional status is one of the typical long-term sequelae of COVID-19 infection that significantly affects the quality of life and work capacity. Minor changes in cardiac structure and function that are unable to cause the manifestation of overt heart failure may remain undetected in COVID-19 convalescents, at the same time potentially contributing to the persistence of symptoms and development of long COVID syndrome.

PURPOSE: To study the typical features and short-term dynamics of cardiac remodeling and possible signs of cardiac dysfunction following hospitalization for COVID-19.

METHODS: This is a combined cross-sectional and longitudinal cohort study in which 176 hospitalized patients (93 female and 83 male, mean age 53.4 ± 13.6 years) with COVID-19 infection underwent comprehensive transthoracic echocardiography pre-discharge (22.6 ± 7.1 days from the onset of symptoms) with repeated evaluation after 1 month. The control group included 88 age-, sex-, height- and weight-matched healthy individuals, with a subset of those (n = 53) matched to the subset of non-hypertensive study participants (n = 106).

RESULTS: Concentric left ventricular geometry was revealed in 59% of participants, including 43% of non-hypertensive subjects; predominantly Grade I diastolic dysfunction was found in 35 and 25% of patients, respectively. Other findings were naturally following from described phenotype of the left venticle and included a mild increase in the absolute and relative wall thickness (0.45 ± 0.07 vs. 0.39 ± 0.04, p < 0.001), worsening of diastolic indices (e' velocity 9.2 ± 2.2 vs. 11.3 ± 2.6 cm/s, p < 0.001, E/e' ratio 7.5 ± 1.8 vs. 6.8 ± 1.7, p = 0.002) and global longitudinal strain (17.5 ± 2.4 vs. 18.6 ± 2.2, p < 0.001). No significant improvement was found on re-evaluation at 1 month.

CONCLUSIONS: Hospitalized patients recovering from COVID-19 were characterized by a high prevalence of left ventricular concentric remodeling, predominantly Grade I diastolic dysfunction, and a mild decrease in the longitudinal systolic function. These changes were less frequent but still prevalent in the non-hypertensive subgroup and largely persisted throughout the 1-month follow-up.}, } @article {pmid38075566, year = {2023}, author = {Wittenberg, S and Vercnocke, J and Chancellor, M and Dhar, S and Liaw, A and Lucas, S and Dhar, N}, title = {Prolonged impacts of COVID-19-associated cystitis: A study on long-term consequences.}, journal = {World journal of clinical cases}, volume = {11}, number = {33}, pages = {7987-7993}, pmid = {38075566}, issn = {2307-8960}, abstract = {BACKGROUND: The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus is an international health concern with substantial morbidity and mortality. COVID-associated cystitis (CAC), presents as new onset or exacerbated urinary symptoms, resembling overactive bladder (OAB) symptoms.

AIM: To examines the long-term outcomes of patients with CAC in the context of Long COVID.

METHODS: A cohort of 350 patients admitted to Detroit Hospitals with COVID-19 between May and December 2020, displaying CAC symptoms following discharge, was prospectively followed. Initial urologic evaluations occurred at 10-14 wk and were repeated at 21-28 mo post-discharge. Symptoms were managed conservatively, employing behavioral modifications and standard OAB medications. Participants completed surveys assessing urinary symptoms and quality of life (QoL) at both time points. The primary outcome was the Urology Care Foundation Overactive Bladder Assessment Tool.

RESULTS: 87% of the final cohort (n = 310) reported symptom improvement at 21-28 mo post-discharge. Patients with new onset CAC symptoms showed a median decrease of 9-10 points in OAB and QoL scores, while those with existing symptoms experienced a decrease of 6 points. Overall, 95.4% of patients with new onset symptoms reported symptom improvement at follow-up, contrasting with 60.7% among those with existing symptoms.

CONCLUSION: This study presents the first long-term follow-up of adult patients with CAC, revealing a promising prognosis with conservative management measures in the context of Long COVID. These findings provide reassurance to patients regarding symptom resolution and underscore the need for further research into this evolving aspect of COVID-19's impact on urological health.}, } @article {pmid38074226, year = {2023}, author = {Banerjee, A and Kumar, S}, title = {Dysautonomia in 'long COVID': Case report.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {10}, pages = {2513-2515}, pmid = {38074226}, issn = {2249-4863}, abstract = {BACKGROUND: The reason for autonomic dysfunction in COVID-19 is yet to get clear, though we tend to notice a few dysautonomia cases during post-COVID-19 manifested most commonly in the form of postural orthostatic tachycardia syndrome (POTS).

CASE PRESENTATION: A case of autonomic dysregulation is presented in a COVID-19 patient as a post-COVID-19 sequelae. On doing an active stand test and two basic autonomic function tests, dysautonomia was diagnosed in the patient, after going through all routine investigations for six months. Cardiac parasympathetic integrity was assessed by measuring the heart rate response to standing by continuous electrocardiographic tracing. The management of these patients is usually conservative.

CONCLUSION: Family physicians must be aware of such cases in future for early diagnosis and management of the patients.}, } @article {pmid38071754, year = {2024}, author = {Torrance, N and MacIver, E and Adams, NN and Skåtun, D and Scott, N and Kennedy, C and Douglas, F and Hernandez-Santiago, V and Grant, A}, title = {Lived experience of work and long COVID in healthcare staff.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {78-85}, pmid = {38071754}, issn = {1471-8405}, support = {COV/LTE/20/32/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; State Medicine ; Delivery of Health Care ; Health Personnel ; }, abstract = {BACKGROUND: Healthcare workers (HCWs) had a greater occupational risk of exposure to coronavirus disease 2019 (COVID-19) and reported higher rates of long COVID (LC). This has implications for the provision of health care in already stretched health services.

AIMS: This study explored the impact of LC on a range of UK National Health Service (NHS) HCWs, their health and well-being, the effect on work patterns, and occupational support received.

METHODS: Mixed-methods study, online survey and qualitative interviews. Participants self-reporting LC symptoms were recruited through social media and NHS channels. Interviews used maximum variation sampling of 50 HCWs including healthcare professionals, ancillary and administration staff. Thematic analysis was conducted using NVivo software.

RESULTS: A total of 471 HCWs completed the online survey. Multiple LC symptoms were reported, revealing activity limitations for 90%. Two-thirds had taken sick leave, 18% were off-work and 33% reported changes in work duties. There were few differences in work practices by occupational group. Most participants were working but managing complex and dynamic symptoms, with periods of improvement and exacerbation. They engaged in a range of strategies: rest, pacing, planning and prioritizing, with work prioritized over other aspects of life. Symptom improvements were often linked to occupational medicine, managerial, colleague support and flexible workplace adjustments.

CONCLUSIONS: LC has a significant impact on the lives of HCWs suffering prolonged symptoms. Due to the variability and dynamic nature of symptoms, workplace support and flexible policies are needed to help retain staff.}, } @article {pmid38071561, year = {2024}, author = {Høeg, TB and Ladhani, S and Prasad, V}, title = {Reliance on the highest-quality studies of Long Covid is appropriate and not evidence of bias.}, journal = {BMJ evidence-based medicine}, volume = {29}, number = {3}, pages = {210-211}, doi = {10.1136/bmjebm-2023-112708}, pmid = {38071561}, issn = {2515-4478}, mesh = {Humans ; *Bias ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid38071530, year = {2024}, author = {Fanshawe, TR}, title = {Correspondence on "How methodological pitfalls have created widespread misunderstanding about long COVID" by Høeg et al.}, journal = {BMJ evidence-based medicine}, volume = {29}, number = {3}, pages = {209}, doi = {10.1136/bmjebm-2023-112675}, pmid = {38071530}, issn = {2515-4478}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Research Design ; }, } @article {pmid38070892, year = {2023}, author = {Loria, V and Aparicio, A and Hildesheim, A and Cortés, B and Barrientos, G and Retana, D and Sun, K and Ocampo, R and Prevots, DR and Zúñiga, M and Waterboer, T and Wong-McClure, R and Morera, M and Butt, J and Binder, M and Abdelnour, A and Calderón, A and Gail, MH and Pfeiffer, RM and Solís, CB and Fantin, R and Vanegas, JC and Mercado, R and Ávila, C and Porras, C and Herrero, R}, title = {Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e071284}, pmid = {38070892}, issn = {2044-6055}, support = {HHSN261201000121C/CP/NCI NIH HHS/United States ; 75N91020C00001/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/epidemiology/prevention & control ; Post-Acute COVID-19 Syndrome ; Costa Rica/epidemiology ; Prospective Studies ; Retrospective Studies ; Antibodies ; Double-Blind Method ; Immunity ; }, abstract = {PURPOSE: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.

PARTICIPANTS: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.

FINDINGS TO DATE: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.

FUTURE PLANS: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.

TRIAL REGISTRATION NUMBER: NCT04537338.}, } @article {pmid38070493, year = {2024}, author = {Green, CE and Leeds, JS and Leeds, CM}, title = {Occupational effects in patients with post-COVID-19 syndrome.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {86-92}, doi = {10.1093/occmed/kqad118}, pmid = {38070493}, issn = {1471-8405}, mesh = {Female ; Humans ; Middle Aged ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Activities of Daily Living ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND: It is well recognized that some individuals experience persistent symptoms following an initial SARS-CoV-2 infection. Symptoms affect physical, cognitive and mental well-being and can adversely impact activities of daily living, including the ability to work.

AIMS: To examine the impact of post-COVID-19 syndrome with respect to effects on quality of life and impact on work in a cohort of people referred to a 'Long COVID' service.

METHODS: All triaged patients (over 18 years with symptoms more than 12 weeks since the initial infection) completed a symptom assessment questionnaire. Occupation and working status (at work, at work struggling with symptoms and off work) were also recorded. Impact on function and quality of life was assessed using the EQ5D5L questionnaire.

RESULTS: A total of 214 patients (median age 51.0 years, 135 females) were seen from January to September 2021. Analysis of occupational status showed: 18% were working, 40% were working but struggling and 35% had stopped working due to symptoms. Those unable to work reported significantly more fatigue, a greater perception of the need for support and lower quality-of-life scores.

CONCLUSIONS: This study shows the extensive impact of post-COVID-19 syndrome on the ability to return to work. Specific return-to-work guidance is needed to support a large proportion of those struggling with the condition. The involvement of the Occupational Health team should form part of the multidisciplinary, collaborative approach to support rehabilitation and improve long-term outcomes for this condition.}, } @article {pmid38069362, year = {2023}, author = {Scheim, DE and Vottero, P and Santin, AD and Hirsh, AG}, title = {Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069362}, issn = {1422-0067}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19 ; Spike Glycoprotein, Coronavirus/metabolism ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Endothelial Cells/metabolism ; *Common Cold ; Angiotensin-Converting Enzyme 2/metabolism ; Polysaccharides/metabolism ; Morbidity ; Hypoxia ; Mammals/metabolism ; }, abstract = {Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus's pathology. SARS-CoV-2 SP attaches to and aggregates red blood cells (RBCs), as shown in many pre-clinical and clinical studies, causing pulmonary and extrapulmonary microthrombi and hypoxia in severe COVID-19 patients. SARS-CoV-2 SP attachments to the heavily sialylated surfaces of platelets (which, like RBCs, have no ACE2) and endothelial cells (having minimal ACE2) compound this vascular damage. Notably, experimentally induced RBC aggregation in vivo causes the same key morbidities as for severe COVID-19, including microvascular occlusion, blood clots, hypoxia and myocarditis. Key risk factors for COVID-19 morbidity, including older age, diabetes and obesity, are all characterized by markedly increased propensity to RBC clumping. For mammalian species, the degree of clinical susceptibility to COVID-19 correlates to RBC aggregability with p = 0.033. Notably, of the five human betacoronaviruses, the two common cold strains express an enzyme that releases glycan attachments, while the deadly SARS, SARS-CoV-2 and MERS do not, although viral loads for COVID-19 and the two common cold infections are similar. These biochemical insights also explain the previously puzzling clinical efficacy of certain generics against COVID-19 and may support the development of future therapeutic strategies for COVID-19 and long COVID patients.}, } @article {pmid38069140, year = {2023}, author = {Pietraszko, P and Zorawski, M and Bielecka, E and Sielatycki, P and Zbroch, E}, title = {Mid-Regional Proadrenomedullin in COVID-19-May It Act as a Predictor of Prolonged Cardiovascular Complications?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069140}, issn = {1422-0067}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Biomarkers ; Adrenomedullin ; *Cardiovascular Diseases/etiology ; }, abstract = {The rising prevalence of cardiovascular disease (CVD) and the impact of the SARS-CoV-2 pandemic have both led to increased mortality rates, affecting public health and the global economy. Therefore, it is essential to find accessible, non-invasive prognostic markers capable of identifying patients at high risk. One encouraging avenue of exploration is the potential of mid-regional proadrenomedullin (MR-proADM) as a biomarker in various health conditions, especially in the context of CVD and COVID-19. MR-proADM presents the ability to predict mortality, heart failure, and adverse outcomes in CVD, offering promise for improved risk assessment and treatment strategies. On the other hand, an elevated MR-proADM level is associated with disease severity and cytokine storms in patients with COVID-19, making it a predictive indicator for intensive care unit admissions and mortality rates. Moreover, MR-proADM may have relevance in long COVID, aiding in the risk assessment, triage, and monitoring of individuals at increased risk of developing prolonged cardiac issues. Our review explores the potential of MR-proADM as a predictor of enduring cardiovascular complications following COVID-19 infection.}, } @article {pmid38069039, year = {2023}, author = {Varillas-Delgado, D and Jimenez-Antona, C and Lizcano-Alvarez, A and Cano-de-la-Cuerda, R and Molero-Sanchez, A and Laguarta-Val, S}, title = {Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {23}, pages = {}, pmid = {38069039}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/genetics ; Longitudinal Studies ; Polymorphism, Genetic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Long COVID-19 syndrome is present in 5-10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infectionA total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility. The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521-8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785-6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19.}, } @article {pmid38068427, year = {2023}, author = {Choi, YJ and Seo, YB and Seo, JW and Lee, J and Nham, E and Seong, H and Yoon, JG and Noh, JY and Cheong, HJ and Kim, WJ and Kim, EJ and Song, JY}, title = {Effectiveness of Antiviral Therapy on Long COVID: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {23}, pages = {}, pmid = {38068427}, issn = {2077-0383}, support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Antiviral treatment reduces the severity and mortality of SARS-CoV-2 infection; however, its effectiveness against long COVID-19 is unclear. This study aimed to evaluate the effectiveness of antiviral drugs in preventing long COVID and related hospitalizations/deaths. Scientific and medical databases were searched from 1 January 2020 to 30 June 2023. We included observational cohort studies comparing individuals receiving early antiviral therapy for COVID-19 and those receiving supportive treatment. A fixed-effects model was used to merge the effects reported in two or more studies. The risk of post-acute sequelae of COVID-19 (PASC) was combined as an odds ratio (OR). Six studies were selected, including a total of 3,352,235 participants. The occurrence of PASC was 27.5% lower in patients who received antiviral drugs during the early stages of SARS-CoV-2 infection (OR = 0.725; 95% confidence interval [CI] = 0.409-0.747) than in the supportive treatment group. Moreover, the risk of PASC-associated hospitalization and mortality was 29.7% lower in patients receiving early antiviral therapy than in the supportive treatment group (OR = 0.721; 95% CI = 0.697-0.794). Early antiviral therapy was associated with a reduced risk of PASC and related hospitalization or death. Thus, early antiviral therapy is recommended for at-risk individuals.}, } @article {pmid38068365, year = {2023}, author = {Jin, W and Hao, W and Shi, X and Fritsche, LG and Salvatore, M and Admon, AJ and Friese, CR and Mukherjee, B}, title = {Using Multi-Modal Electronic Health Record Data for the Development and Validation of Risk Prediction Models for Long COVID Using the Super Learner Algorithm.}, journal = {Journal of clinical medicine}, volume = {12}, number = {23}, pages = {}, pmid = {38068365}, issn = {2077-0383}, support = {K08 HL155407/HL/NHLBI NIH HHS/United States ; P30 CA046592/CA/NCI NIH HHS/United States ; P30CA046592/NH/NIH HHS/United States ; K08HL155407/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Post-Acute Sequelae of COVID-19 (PASC) have emerged as a global public health and healthcare challenge. This study aimed to uncover predictive factors for PASC from multi-modal data to develop a predictive model for PASC diagnoses.

METHODS: We analyzed electronic health records from 92,301 COVID-19 patients, covering medical phenotypes, medications, and lab results. We used a Super Learner-based prediction approach to identify predictive factors. We integrated the model outputs into individual and composite risk scores and evaluated their predictive performance.

RESULTS: Our analysis identified several factors predictive of diagnoses of PASC, including being overweight/obese and the use of HMG CoA reductase inhibitors prior to COVID-19 infection, and respiratory system symptoms during COVID-19 infection. We developed a composite risk score with a moderate discriminatory ability for PASC (covariate-adjusted AUC (95% confidence interval): 0.66 (0.63, 0.69)) by combining the risk scores based on phenotype and medication records. The combined risk score could identify 10% of individuals with a 2.2-fold increased risk for PASC.

CONCLUSIONS: We identified several factors predictive of diagnoses of PASC and integrated the information into a composite risk score for PASC prediction, which could contribute to the identification of individuals at higher risk for PASC and inform preventive efforts.}, } @article {pmid38066618, year = {2023}, author = {Krotz, A and Sosnowsky-Waschek, N and Bechtel, S and Neumann, C and Lohkamp, M and Kovacs, G and Genser, B and Fischer, JE}, title = {Reducing sick leave, improving work ability, and quality of life in patients with mild to moderate Long COVID through psychosocial, physiotherapeutic, and nutritive supportive digital intervention (MiLoCoDaS): study protocol for a randomized controlled trial.}, journal = {Trials}, volume = {24}, number = {1}, pages = {798}, pmid = {38066618}, issn = {1745-6215}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Sick Leave ; Work Capacity Evaluation ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Following SARS-CoV-2 infection, a relevant proportion of patients suffer from persistent or recurring sequela, even after initially mild primary illness. Many patients experience exhaustion and fatigue, rendering them incapable of working. Long COVID exerts a substantial burden on society and the healthcare system: at least 65 million people are currently affected worldwide. The underlying pathobiology is a complex derangement in several organ systems. To date, causal pharmaceutical therapies remain elusive. Waiting lists for specialist care are long. Rapidly scalable digital interventions offering support for the frequent subgroup of patients with mild to moderate impairment from Long COVID are urgently needed. The MiLoCoDaS study compares three intensities of a potentially rapidly scalable digital intervention aiming to accelerate recovery. The overall objective is to figure out if there is a difference in the effect sizes between these modalities.

METHODS: The online intervention uses a learning platform (LMS, TYPO3 framework) comprising 12 sessions of medical, psychological, physiotherapeutic, and nutritional content. The three modalities differ as follows: patient information only (sham intervention, control), information plus interactive digital workbook including practical exercises (digital intervention), and the digital workbook augmented by once-weekly online seminars and discussion groups (person and peer-contact). Eligible patients are 18-67 years old satisfying Long COVID diagnostic criteria. Patients are recruited through primary care physicians and randomly allocated. The primary endpoint is the number of sick leave days during the 6-month observation period; secondary endpoints are patient-reported symptoms, quality of life, and work ability. The study size provides a power of 80% at a type I error of < 0.05 to show an effect size of Cohen = 0.3 between the augmented and the sham intervention (N = 152 per arm, total accounting for attrition N = 600).

DISCUSSION: If one of the two interventions is superior to providing information alone, MiLoCoDaS would provide the starting point for a rapidly scalable digital intervention for the frequent and currently underserved patient group with mild to moderate impairment from Long COVID. Several caveats pertain to the heterogeneity of Long COVID manifestation and duration prior to inclusion. It is conceivable that the possible effect of the intervention may differ across subgroups. Therefore, a priori defined secondary analysis will be conducted.

TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028964. Registered on 24 August 2022.}, } @article {pmid38066589, year = {2023}, author = {Aschman, T and Wyler, E and Baum, O and Hentschel, A and Rust, R and Legler, F and Preusse, C and Meyer-Arndt, L and Büttnerova, I and Förster, A and Cengiz, D and Alves, LGT and Schneider, J and Kedor, C and Bellmann-Strobl, J and Sanchin, A and Goebel, HH and Landthaler, M and Corman, V and Roos, A and Heppner, FL and Radbruch, H and Paul, F and Scheibenbogen, C and Dengler, NF and Stenzel, W}, title = {Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles.}, journal = {Acta neuropathologica communications}, volume = {11}, number = {1}, pages = {193}, pmid = {38066589}, issn = {2051-5960}, support = {KA1-Co-02 'COVIPA'//Helmholtz association Initiative and Networking Fund grant/ ; KA1-Co-02 'COVIPA'//Helmholtz association Initiative and Networking Fund grant/ ; KA1-Co-02 'COVIPA'//Helmholtz Association Initiative and Networking Fund grant/ ; }, mesh = {Humans ; *Capillaries ; *COVID-19 ; SARS-CoV-2 ; Muscle, Skeletal ; Fatigue ; }, abstract = {The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as "long COVID". Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169[+] macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.}, } @article {pmid38065769, year = {2024}, author = {Yu, Y and Zhang, X and Lau, MMC and Lau, JTF}, title = {The intention to get COVID-19 booster vaccination and its association with cognitive and emotional factors: A survey of Chinese COVID-19 infected people in Hong Kong.}, journal = {Vaccine}, volume = {42}, number = {2}, pages = {206-212}, doi = {10.1016/j.vaccine.2023.12.015}, pmid = {38065769}, issn = {1873-2518}, mesh = {Hong Kong/epidemiology ; *COVID-19/epidemiology/prevention & control ; China ; Cognition ; East Asian People ; Immunization, Secondary ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; *COVID-19 Vaccines/administration & dosage ; Humans ; *Intention ; Emotions ; }, abstract = {BACKGROUND: Although the pandemic has ended officially, COVID-19 remains impactful. Booster COVID-19 vaccination is still needed to protect individuals against COVID-19 and the disease's harmful consequences. This study investigated the prevalence of the intention to get booster COVID-19 vaccination after receiving the COVID-19 diagnosis and its associated factors among people reporting prior COVID-19.

METHODS: A population-based anonymous telephone survey was conducted in Hong Kong, China from June to August 2022 among Chinese people reporting prior COVID-1 between February and August 2022 and having taken up ≥2 doses of COVID-19 vaccines prior to COVID-19 diagnosis.

RESULTS: The prevalence of the intention to get booster vaccination was 59.2 %. Older age (>60 years), being currently married, not employed full-time, and having chronic diseases were positively associated with the intention to get booster vaccination. Adjusted for the background factors, higher levels of the cognitive factors of perceived susceptibility to COVID-19, perceived acquired moderate-to-strong immunity against COVID-19, and perceived adequate knowledge of COVID-19 were positively associated with the intention to get booster vaccination; stronger perceived severity of prior infection despite vaccination was negatively associated with the intention outcome. In contrast, stronger mental distress due to COVID-19, illness concern, and emotional representation were positively associated with the intention. Self-perceived long COVID status was not a significant factor.

DISCUSSION: The prevalence of the intention to get booster COVID-19 vaccination was limited, especially among younger people reporting prior COVID-19. Health promotion is still required among people reporting prior COVID-19 and may emphasize the significant cognitive factors positively associated with the intention. Future studies are needed to confirm the findings, clarify the role of emotional factors on booster vaccination, and explore other factors of the intention to get booster vaccination among people reporting prior COVID-19.}, } @article {pmid38063895, year = {2024}, author = {Shil, RSK and Hughes, TW and Sargent, BF and Huang, Y and Tamborska, AA and Frank, B and Ellul, MA and Michael, BD}, title = {A clinical approach to the investigation and management of long COVID associated neuropathic pain.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1787-1795}, pmid = {38063895}, issn = {1433-8491}, support = {MC_PC_19059/MRF/MRF/United Kingdom ; MR/V007181/1/MRF/MRF/United Kingdom ; ISSF201902/3/WT_/Wellcome Trust/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; NIHR133599//National Institute for Health and Care Research/ ; /WT_/Wellcome Trust/United Kingdom ; MR/V03605X/1/MRC_/Medical Research Council/United Kingdom ; MR/V007181/1/MRC_/Medical Research Council/United Kingdom ; MR/T028750/1/MRC_/Medical Research Council/United Kingdom ; MR/V03605X/1/MRF/MRF/United Kingdom ; MRF-CPP-R2-2022-100003/MRF/MRF/United Kingdom ; MR/T028750/1/MRF/MRF/United Kingdom ; }, mesh = {Humans ; *COVID-19/complications ; *Neuralgia/etiology/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {COVID-19 has been associated with a wide range of ongoing symptoms following recovery from the acute SARS-CoV-2 infection. Around one in three people with COVID-19 develop neurological symptoms with many reporting neuropathic pain and associated symptoms, including paraesthesia, numbness, and dysesthesia. Whilst the pathophysiology of long COVID-19-associated neuropathic pain remains unclear, it is likely to be multifactorial. Early identification, exclusion of common alternative causes, and a biopsychosocial approach to the management of the symptoms can help in relieving the burden of disease and improving the quality of life for patients.}, } @article {pmid38063653, year = {2023}, author = {Overall, B and Langley, K and Douglass, J}, title = {Manual Lymph Drainage for Post-COVID-19 Related Cough, Breathlessness, and Fatigue; Two Case Reports.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {23}, pages = {}, pmid = {38063653}, issn = {2227-9032}, abstract = {BACKGROUND: Persistent symptoms after SARS CoV-2 infection such as fatigue, shortness of breath, and cognitive dysfunction that cannot be explained by an alternative diagnosis have been termed long COVID and present a significant emerging public health problem. Current approaches include rehabilitation and symptom management involving multiple health disciplines and as yet there are no pharmaceutical approaches other than routine symptom management. Manual lymph drainage (MLD) has been used to support recovery during pulmonary rehabilitation and reduce chronic inflammation including symptoms associated with long COVID.

CASE DESCRIPTION AND OUTCOMES: Two adult females who had reported long-COVID symptoms more than 10 weeks after the resolution of the acute infection were treated with MLD by Remedial Therapists trained in the Dr Vodder method of MLD. Respiratory function (Peak Flow Meter) and blood oxygen levels (Oximeter) were recorded before and after a one-minute sit-to-stand test prior to the treatment. The Dyspnea-12 Questionnaire, the Revised Piper Fatigue Scale, and Likert scales were used to collect client-reported outcomes. Six 45-min treatments were applied weekly, with a follow-up review and treatment at three months. In both cases, all outcomes improved after the third treatment with further improvement noted at three months.

CONCLUSIONS: MLD may offer a non-invasive, non-pharmaceutical approach to the resolution of long-COVID symptoms such as cough, breathlessness, and fatigue.}, } @article {pmid38063359, year = {2023}, author = {Ghram, A and Latiri, I and Methnani, J and Souissi, A and Benzarti, W and Toulgui, E and Ben Saad, H}, title = {Effects of cardiorespiratory rehabilitation program on submaximal exercise in patients with long-COVID-19 conditions: a systematic review of randomized controlled trials and recommendations for future studies.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {12}, pages = {1095-1124}, doi = {10.1080/17476348.2023.2293226}, pmid = {38063359}, issn = {1747-6356}, mesh = {Humans ; *Cardiac Rehabilitation/methods ; *COVID-19/rehabilitation ; Exercise Therapy/methods ; *Exercise Tolerance ; Post-Acute COVID-19 Syndrome ; *Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Walk Test ; }, abstract = {INTRODUCTION: Long-COVID-19 patients (LC19Ps) often experience cardiovascular and respiratory complications. Cardiorespiratory rehabilitation programs (CRRPs) have emerged as promising interventions to enhance exercise capacity in this population. This systematic review aimed to assess the impact of CRRPs on submaximal exercise performance, specifically the 6-minute walk test (6MWT) outcomes, in LC19Ps through an analysis of available randomized controlled trials (RCTs).

METHODS: A systematic search was conducted in PubMed/Medline and Scopus to identify relevant RCTs. Six RCTs meeting inclusion criteria were included in this review, investigating the effects of CRRPs on 6MWT outcomes in LC19Ps.

RESULTS: The findings from the included RCTs provide compelling evidence supporting the effectiveness of CRRPs in improving submaximal exercise performance in LC19Ps. These results underscore the potential of CRRPs to enhance submaximal exercise capacity and overall functional well-being in this population. However, future research is imperative to determine optimal CRRPs, including duration, intensity, and specific intervention components. Additionally, the long-term sustainability and durability of CRRP-induced improvements warrant further exploration. Future studies should prioritize patient-centric outcomes and address potential implementation barriers.

CONCLUSION: CRRPs show promise in ameliorating submaximal exercise performance among LC19Ps. Further research is needed to refine these programs and ensure their lasting impact on this patient group.

https://doi.org/10.17605/OSF.IO/HMN38. [Figure: see text].}, } @article {pmid38062429, year = {2023}, author = {Ye, Y and Xiong, C and Dai, Y and Wang, Y and Yang, X and Cheng, L and Hou, C and Nie, N and Tang, H and Ma, X and Zhang, A and Cao, G and He, Y and Jiang, J and Li, L}, title = {Assessment of post-COVID-19 fatigue among female survivors 2 years after hospital discharge: a nested case-control study.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {2455}, pmid = {38062429}, issn = {1471-2458}, support = {2020FYYX213//Joint Scientific Research Project of the Chongqing Health Commission and the Science and Technology Commission/ ; cstc2020jcyjjqX0014//Outstanding Youth Science Fund of Chongqing/ ; CQYC202005003//Chongqing Talent Fund/ ; SKLYQ202102//Open Project Program of the State Key Laboratory of Trauma, Burn and Combined Injury/ ; 82272908//National Natural Science Foundation of China/ ; 2023NSCQ-JQX0190//National Natural Science Foundation of Chongqing/ ; }, mesh = {Humans ; Male ; Female ; Depression/etiology ; Patient Discharge ; *COVID-19/epidemiology ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Fatigue/epidemiology/etiology ; Anxiety/etiology ; Survivors ; *Cerebrovascular Disorders ; }, abstract = {BACKGROUND: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue.

METHODS: This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis.

RESULTS: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10.

CONCLUSION: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.}, } @article {pmid38061788, year = {2023}, author = {Sherwood, O}, title = {Hancock's covid inquiry evidence offers few clues as to why long covid was sidelined.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2902}, doi = {10.1136/bmj.p2902}, pmid = {38061788}, issn = {1756-1833}, } @article {pmid38061134, year = {2024}, author = {Jakwerth, CA and Grass, V and Erb, A and Pichlmair, A and Boonen, G and Butterweck, V and Schmidt-Weber, CB}, title = {Inhibition of SARS-CoV-2 infection and replication by Petasites hybridus CO2-extract (Ze 339).}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {170}, number = {}, pages = {115959}, doi = {10.1016/j.biopha.2023.115959}, pmid = {38061134}, issn = {1950-6007}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Petasites ; Carbon Dioxide ; Post-Acute COVID-19 Syndrome ; Virus Replication ; }, abstract = {BACKGROUND: The intensified search for low-threshold herbal anti-viral drugs would be of great advantage in prevention of early stages of infection. Since the SARS-CoV-2 Omicron variant has prevailed in western countries, the course has only been mild, but there are still no widely available drugs that can alleviate or shorten disease progression and counteract the development of Long-COVID. This study aimed to investigate the antiviral effects of a CO2-extract from Petasites hybridus (Ze 339).

METHODS: We analyzed the infection and replication rate of SARS-CoV-2 in primary normal human bronchial epithelial cells (NHBEs) using a GFP-expressing version of the wild-type SARS-CoV-2 virus and live cell imaging. Upon infection with a clinical isolate of the Omicron variant, viral RNA content was quantified, and plaque assays were performed. In addition, the human transcriptome was analyzed after 4- and 24-hours post infection using whole genome microarrays.

RESULTS: Ze 339 had a protective effect on primary airway epithelial cells during SARS-CoV-2 infection and impeded SARS-CoV-2 infection and replication in NHBE. Notably, Ze 339 inhibited the expression of infection-induced IFNA10 by 8.6-fold (p < 0.05) and additionally reduced a wide range of other interferons (IFNA6, IFNA7, IFNA8, IFNA21, IFNE, IFNW1).

CONCLUSION: Thereby, Ze 339 attenuated epithelial infection by SARS-CoV-2 and modeled the IFN response. In conclusion, this study highlights Ze 339 as a potential treatment option for COVID-19 that limits infection-associated cell intrinsic immune responses.}, } @article {pmid38059400, year = {2024}, author = {Choudhary, S and Nehul, S and Singh, A and Panda, PK and Kumar, P and Sharma, GK and Tomar, S}, title = {Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting main protease and papain-like protease.}, journal = {IUBMB life}, volume = {76}, number = {5}, pages = {228-241}, doi = {10.1002/iub.2793}, pmid = {38059400}, issn = {1521-6551}, support = {IPA/2020/000054//Science and Engineering Research Board, Department of Science & Technology, Government of India/ ; }, mesh = {*SARS-CoV-2/drug effects/immunology ; *Antiviral Agents/pharmacology ; Humans ; *COVID-19 Drug Treatment ; Triterpenes/pharmacology/chemistry ; COVID-19/virology/immunology ; Coronavirus 3C Proteases/antagonists & inhibitors/metabolism ; Coronavirus Papain-Like Proteases/antagonists & inhibitors/metabolism ; Cytokines/metabolism ; Molecular Docking Simulation ; Immunologic Factors/pharmacology ; Anti-Inflammatory Agents/pharmacology ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules targeting the SARS-CoV-2 virus-specific proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50) values ranging from 1.42 to 32.7 μM. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin, exhibit potent anti-SARS-CoV-2 activity in cell-based assays, with half-maximum effective concentration (EC50) values of 21.73 and 31.19 μM, respectively. The anti-inflammatory roles of azadirachtin and withanolide_A when assessed using HEK293T cells, were found to significantly reduce the levels of CXCL10, TNFα, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-α1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2-specific enzymes and also host immune pathways involved in virus-mediated inflammation.}, } @article {pmid38058998, year = {2023}, author = {Shi, W and Jiang, D and Rando, H and Khanduja, S and Lin, Z and Hazel, K and Pottanat, G and Jones, E and Xu, C and Lin, D and Yasar, S and Cho, SM and Lu, H}, title = {Blood-brain barrier breakdown in COVID-19 ICU survivors: an MRI pilot study.}, journal = {NeuroImmune pharmacology and therapeutics}, volume = {2}, number = {4}, pages = {333-338}, pmid = {38058998}, issn = {2750-6665}, support = {P41 EB031771/EB/NIBIB NIH HHS/United States ; R01 NS106702/NS/NINDS NIH HHS/United States ; R01 NS106711/NS/NINDS NIH HHS/United States ; RF1 AG071515/AG/NIA NIH HHS/United States ; P50 HD103538/HD/NICHD NIH HHS/United States ; K23 HL157610/HL/NHLBI NIH HHS/United States ; R01 AG064792/AG/NIA NIH HHS/United States ; U01 NS100588/NS/NINDS NIH HHS/United States ; UF1 NS100588/NS/NINDS NIH HHS/United States ; }, abstract = {OBJECTIVES: Coronavirus disease 2019 (COVID-19) results in severe inflammation at the acute stage. Chronic neuroinflammation and abnormal immunological response have been suggested to be the contributors to neuro-long-COVID, but direct evidence has been scarce. This study aims to determine the integrity of the blood-brain barrier (BBB) in COVID-19 intensive care unit (ICU) survivors using a novel MRI technique.

METHODS: COVID-19 ICU survivors (n=7) and age and sex-matched control participants (n=17) were recruited from June 2021 to March 2023. None of the control participants were hospitalized due to COVID-19 infection. The COVID-19 ICU survivors were studied at 98.6 ± 14.9 days after their discharge from ICU. A non-invasive MRI technique was used to assess the BBB permeability to water molecules, in terms of permeability surface area-product (PS) in the units of mL/100 g/min.

RESULTS: PS was significantly higher in COVID-19 ICU survivors (p=0.038) when compared to the controls, with values of 153.1 ± 20.9 mL/100 g/min and 132.5 ± 20.7 mL/100 g/min, respectively. In contrast, there were no significant differences in whole-brain cerebral blood flow (p=0.649) or brain volume (p=0.471) between the groups.

CONCLUSIONS: There is preliminary evidence of a chronic BBB breakdown in COVID-19 survivors who had a severe acute infection, suggesting a plausible contributor to neurological long-COVID symptoms.}, } @article {pmid38058684, year = {2023}, author = {Goldstein Ferber, S and Weller, A and Hayes, AM and Vannorsdall, TD and Ajlouni, Y and Qudah, M and Zalsman, G and Shoval, G and Jannini, TB and Fiedler, R and Chen, LX and Shayani, DR and Kachuki Dory, E and Stolowicz-Melman, D and Evans, C and Trow, M and Di Lorenzo, G and Rossi, R}, title = {International study of the Complex Stress Reaction Syndrome: Implications for transdiagnostic clinical practice.}, journal = {World journal of psychiatry}, volume = {13}, number = {10}, pages = {803-815}, pmid = {38058684}, issn = {2220-3206}, abstract = {BACKGROUND: The debate regarding diagnostic classification systems in psychiatry (categorial vs dimensional systems) has essential implications for the diagnosis, prevention and treatment of stress reactions. We previously found a unique pattern of stress reaction in a study executed during the coronavirus disease 2019 pandemic using large representative samples in two countries, and termed it the Complex Stress Reaction Syndrome (CSRS).

AIM: To investigate CSRS, Type A (psychiatric symptoms, spanning anxiety, depression, stress symptoms, and post-traumatic stress disorder (PTSD)), with or without long-coronavirus disease (COVID) residuals (CSRS, Type B, neuropsychiatric symptoms spanning cognitive deficits and fatigue, excluding systemic symptoms). Our two-tailed hypothesis was that CSRS is a condition related to an unrecognized type of stress reaction in daily life in the general population (Type A) or that it is related to the severe acute respiratory syndrome coronavirus 2 infection and its long-COVID residuals (Type B).

METHODS: 977 individuals in four continents (North America, Europe, Australia and the Middle East) completed the online study questionnaire in six languages using the Qualtrics platform. The study was managed by six teams in six countries that promoted the study on social media. The questionnaire assessed anxiety, depression, stress symptoms and PTSD (CSRS, Type A), cognitive deficits and fatigue (CSRS, Type B). The data were analyzed using Proportion Analyses, Multivariate Analysis of Co-Variance (MANCOVA), linear regression analyses and validated clinical cutoff points.

RESULTS: The results of the Proportion Analyses showed that the prevalence of 4 symptoms spanning anxiety, depression, stress symptoms, and PTSD was significantly higher than the most prevalent combinations of fewer symptoms across 4 continents, age groups, and gender. This supports the transdiagnostic argument embedded in the CSRS (Type A). The same pattern of results was found in infected/recovered individuals. The prevalence of the 4 psychiatric symptoms combination was significantly greater than that of 5 and 6 symptoms, when adding cognitive deficits and fatigue, respectively. MANCOVA showed a significant three-way interaction (age × gender × continent). Further analyses showed that the sources of this three-way interaction were threefold relating to two sub-populations at-risk: (1) Individuals that self-identified as non-binary gender scored significantly higher on all 4 psychiatric symptoms of the CSRS, Type A at young age groups (< 50 years old) in North America compared to (self-identified) women and men located in the 4 continents studied, and to other ages across the adult life span; and (2) This pattern of results (CSRS, Type A) was found also in women at young ages (< 40 years old) in North America who scored higher compared to men and women in other continents and other ages. Linear regression analyses confirmed the MANCOVA results.

CONCLUSION: These results show a combined mental health risk factor related to stress reactivity, suggesting that the CSRS is sensitive to populations at risk and may be applied to future identification of other vulnerable sub-populations. It also supports the transdiagnostic approach for more accurate prevention and treatment. Time will tell if such transdiagnostic syndromes will be part of the discussions on the next revisions of the traditional classification systems or whether the crisis in psychiatry further evolves.}, } @article {pmid38057338, year = {2023}, author = {Frallonardo, L and Segala, FV and Chhaganlal, KD and Yelshazly, M and Novara, R and Cotugno, S and Guido, G and Papagni, R and Colpani, A and De Vito, A and Barbagallo, M and Madeddu, G and Babudieri, S and Lochoro, P and Ictho, J and Putoto, G and Veronese, N and Saracino, A and Di Gennaro, F}, title = {Incidence and burden of long COVID in Africa: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {21482}, pmid = {38057338}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Incidence ; *Mental Disorders/epidemiology ; Africa/epidemiology ; }, abstract = {Long COVID, also known as "post-acute sequelae of COVID-19," affects at least 65 million individuals worldwide with a wide spectrum of symptoms that may last weeks, months, or permanently. Its epidemiology and burden in Africa are unclear. This meta-analysis examines long-term COVID-19 effects in the WHO African Region. A systematic search in several databases was carried out up to 12 February 2023 including observational studies from African countries reporting the cumulative incidence of long COVID signs and symptoms. Only studies conducted in African countries were included. Several sensitivity and meta-regression analyses were performed. Among 1547 papers initially screened, 25 were included, consisting of 29,213 participants. The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4-59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25% (95% CI 21.1-30.4). Higher age (p = 0.027) and hospitalization (p = 0.05) were associated with a higher frequency of long COVID. Long COVID poses a significant burden in Africa, particularly concerning psychiatric conditions. The study recommends identifying at-risk people and defining treatment strategies and recommendations for African long-COVID patients. High-quality studies addressing this condition in African setting are urgently needed.}, } @article {pmid38057315, year = {2023}, author = {Liu, X and Xiong, W and Ye, M and Lu, T and Yuan, K and Chang, S and Han, Y and Wang, Y and Lu, L and Bao, Y}, title = {Non-coding RNAs expression in SARS-CoV-2 infection: pathogenesis, clinical significance, and therapeutic targets.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {441}, pmid = {38057315}, issn = {2059-3635}, mesh = {Humans ; *COVID-19/genetics ; Post-Acute COVID-19 Syndrome ; Clinical Relevance ; SARS-CoV-2/genetics ; RNA, Untranslated/genetics ; Biomarkers ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been looming globally for three years, yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Host non-coding RNAs (ncRNAs) display aberrations in the context of COVID-19. Specifically, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) exhibit a close association with viral infection and disease progression. In this comprehensive review, an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development, encompassing viral invasion, replication, immune response, and multiorgan deficits which include respiratory system, cardiac system, central nervous system, peripheral nervous system as well as long COVID. Furthermore, we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19, such as stratification biomarkers, prognostic biomarkers, and predictive biomarkers for treatment response. In addition, we also discuss the therapeutic potential of ncRNAs for COVID-19, presenting ncRNA-based strategies to facilitate the development of novel treatments. Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis, we hope to offer valuable insights into the stratification, prognosis, and treatment of COVID-19.}, } @article {pmid38057245, year = {2024}, author = {Quinn, J}, title = {Long COVID autonomic syndrome: Improved understanding through translational research.}, journal = {European journal of internal medicine}, volume = {120}, number = {}, pages = {34-35}, doi = {10.1016/j.ejim.2023.11.023}, pmid = {38057245}, issn = {1879-0828}, mesh = {Humans ; *Translational Research, Biomedical ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38057014, year = {2023}, author = {Ramírez-Vélez, R and Oscoz-Ochandorena, S and García-Alonso, Y and García-Alonso, N and Legarra-Gorgoñon, G and Oteiza, J and Lorea, AE and Izquierdo, M and Correa-Rodríguez, M}, title = {Maximal oxidative capacity during exercise is associated with muscle power output in patients with long coronavirus disease 2019 (COVID-19) syndrome. A moderation analysis.}, journal = {Clinical nutrition ESPEN}, volume = {58}, number = {}, pages = {253-262}, doi = {10.1016/j.clnesp.2023.10.009}, pmid = {38057014}, issn = {2405-4577}, mesh = {Humans ; *Adipose Tissue/metabolism ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Exercise/physiology ; Muscle, Skeletal/metabolism ; Oxidative Stress ; }, abstract = {BACKGROUND & AIMS: Long COVID syndrome (LCS) involves persistent symptoms experienced by many patients after recovering from coronavirus disease 2019 (COVID-19). We aimed to assess skeletal muscle energy metabolism, which is closely related to substrate oxidation rates during exercise, in patients with LCS compared with healthy controls. We also examined whether muscle power output mediates the relationship between COVID-19 and skeletal muscle energy metabolism.

METHODS: In this cross-sectional study, we enrolled 71 patients with LCS and 63 healthy controls. We assessed clinical characteristics such as body composition, physical activity, and muscle strength. We used cardiopulmonary exercise testing to evaluate substrate oxidation rates during graded exercise. We performed statistical analyses to compare group characteristics and peak fat oxidation differences based on power output.

RESULTS: The two-way analysis of covariance (ANCOVA) results, adjusted for covariates, showed that the patients with LCS had lower absolute maximal fatty acid oxidation (MFO), relative MFO/fat free mass (FFM), absolute carbohydrates oxidation (CHox), relative CHox/FFM, and oxygen uptake (V˙˙O2) at maximum fat oxidation (g min[-1]) than the healthy controls (P < 0.05). Moderation analysis indicated that muscle power output significantly influenced the relationship between LCS and reduced peak fat oxidation (interaction β = -0.105 [95% confidence interval -0.174; -0.036]; P = 0.026). Therefore, when muscle power output was below 388 W, the effect of the LCS on MFO was significant (62% in our study sample P = 0.010). These findings suggest compromised mitochondrial bioenergetics and muscle function, represented by lower peak fat oxidation rates, in the patients with LCS compared with the healthy controls.

CONCLUSION: The patients with LCS had lower peak fat oxidation during exercise compared with the healthy controls, potentially indicating impairment in skeletal muscle function. The relationship between peak fat oxidation and LCS appears to be mediated predominantly by muscle power output. Additional research should continue investigating LCS pathogenesis and the functional role of mitochondria.}, } @article {pmid38056494, year = {2023}, author = {Schüring, S and Widera, T}, title = {[Assessment of Long COVID in Medical Rehabilitation].}, journal = {Die Rehabilitation}, volume = {62}, number = {6}, pages = {331-338}, doi = {10.1055/a-2186-5422}, pmid = {38056494}, issn = {1439-1309}, mesh = {Humans ; *COVID-19 ; Germany/epidemiology ; *Post-Acute COVID-19 Syndrome/rehabilitation ; Rehabilitation Centers ; }, abstract = {PURPOSE: The aim of the study was to provide an insight into the care situation of long COVID patients in inpatient medical rehabilitation facilities in Germany.

METHODS: For this purpose, a standardized online survey was conducted among 1,080 inpatient medical rehabilitation facilities in Germany.

RESULTS: A total of 338 cases were available for the analysis. Of these, 173 (51%) reported treating long COVID. The cumulative total number of rehabilitants with long COVID treated in the facilities up to the time of the survey was 11,948. The results showed that rehabilitation facilities were mostly prepared for the care of patients with Long COVID. Lack of capacity was reported especially by those rehabilitation facilities that treated rehabilitants with long COVID in pneumology departments. Furthermore, capacity bottlenecks were related to the total number of patients with long COVID in the rehabilitation facility ("proportion of rehabilitants with long COVID to all rehabilitants in the department"). Heterogeneity was found in the treatment concept for long COVID and the allocation of patients to a specific department.

CONCLUSION: The results of the long COVID inventory underline the importance of medical rehabilitation in the treatment of the long-term health and participation-related consequences of COVID-19.}, } @article {pmid38056307, year = {2024}, author = {Figueiredo, B and Sheahan, J and Luo, S and Bird, S and Wong Lit Wan, D and Xenos, S and Itsiopoulos, C and Jessup, R and Zheng, Z}, title = {Journey mapping long COVID: Agency and social support for long-hauling.}, journal = {Social science & medicine (1982)}, volume = {340}, number = {}, pages = {116485}, doi = {10.1016/j.socscimed.2023.116485}, pmid = {38056307}, issn = {1873-5347}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Social Support ; Coping Skills ; }, abstract = {Long COVID, also known as Post COVID-19 condition, is defined by the WHO as the continuation or development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation. Despite many studies examining the causes and mechanisms of this disease, fewer studies have sought to understand the experience of those suffering from long COVID, or "long-haulers," This study contributes to the understanding of long-haulers (N = 14) by examining the role of agency and social support in shaping their journeys with long COVID. Drawing on a combination of interviews, questionnaires, and video diaries over a three-month period, journey mapping was used to document the participants' experiences, including symptoms, coping strategies, and lifestyle changes. Analysis of these journey maps resulted in a framework with four clusters demonstrating the importance of social support and patient agency shaping participants' Long COVID trajectory; the study contributes valuable insights into the daily lives and challenges individuals face with long COVID, informing the development of targeted support programs.}, } @article {pmid38055787, year = {2024}, author = {Lieberwerth, M and Niemeijer, A}, title = {Lost and changed meaning in life of people with Long Covid: a qualitative study.}, journal = {International journal of qualitative studies on health and well-being}, volume = {19}, number = {1}, pages = {2289668}, doi = {10.1080/17482631.2023.2289668}, pmid = {38055787}, issn = {1748-2631}, mesh = {Humans ; Chronic Disease ; Communicable Disease Control ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; Qualitative Research ; }, abstract = {Long Covid (LC) has been called the greatest mass-disabling event in human history. For patients, LC not only has implications for quality of life but also for meaning in life: how one's life and the world are understood and what is seen as valuable in one's life. This qualitative empirical study used a Constructivist Grounded Theory approach to investigate the meaning in life of people struggling with LC through ten patient interviews. This study shows that patients lose their prior understanding of life and come to a changed meaning in life, in part due to the experienced (social) isolation and loss of (both physical and cognitive) abilities caused by LC. Moreover, patients struggled with acceptance, uncertainty, and the inherent incomprehensibility and uncontrollability that living with LC entails, though this simultaneously co-existed with hope, optimism and acceptance. Additionally, dimensions of meaning intersect; a patient having some understanding of their illness (dimension of meaning: comprehension) required an understanding Other (dimension of meaning: connection). Emerging from lockdown brought the challenge and isolation of adjusting to chronic illness in society as usual (albeit divided about COVID-19 measures). This study thus offers novel insights regarding changed, present, and sought meaning in life for LC patients.}, } @article {pmid38055615, year = {2024}, author = {Seehuus, M and Fertig, M and Handy, AB and Clifton, J and Stanton, AM}, title = {The impact of COVID-19 and long COVID on sexual function in cisgender women.}, journal = {The journal of sexual medicine}, volume = {21}, number = {2}, pages = {129-144}, doi = {10.1093/jsxmed/qdad155}, pmid = {38055615}, issn = {1743-6109}, mesh = {Adult ; Male ; Female ; Humans ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; *COVID-19/complications ; *Sexual Dysfunction, Physiological/epidemiology/etiology/psychology ; Orgasm ; Sexual Behavior/psychology ; *Sexual Dysfunctions, Psychological/epidemiology/etiology/diagnosis ; }, abstract = {BACKGROUND: Research suggests that COVID-19 impairs sexual function in men, but little is known about the impact of COVID-19 (or long COVID) on sexual function in women.

AIM: We sought to compare the sexual function of cisgender women who had never had COVID-19, who had COVID-19 but not long COVID, and who had long COVID, and assessed whether long COVID symptoms and/or emotional distress mediate the relationship between COVID-19 history and sexual function.

METHODS: In total, 2329 adult cisgender women were recruited online as study participants. Half of these women reported having had COVID-19, and the other half reported never having had COVID-19. Of those who had COVID-19, 25% (n = 170) reported having long COVID. We compared the mean Female Sexual Function Index (FSFI) scores by using t-tests for each of the primary comparison categories (never COVID vs COVID and only COVID vs long COVID). Four path models were used to test the hypotheses that (1) long COVID symptoms or (2) depression, anxiety, and/or stress assessed with the subscales of the 21-item Depression, Anxiety, and Stress Scale (DASS-21) mediated the relationship between COVID-19 and sexual function.

OUTCOMES: Sexual function was measured with the FSFI, long COVID symptoms were assessed using the Centers for Disease Control working symptom set, and emotional distress was measured with the DASS-21.

RESULTS: In total, 1313 participants provided data suitable for analysis. The never-COVID group (n = 645, 49.1%) had higher scores on the Desire, Arousal, Lubrication, and Satisfaction subscales of the FSFI (mean [M] [SD] FSFI total Mnever COVID = 27.98 [4.84] vs MCOVID = 27.05 [5.21]) than the combined only-COVID (n = 498, 37.9%) and long-COVID (n = 170, 12.9%) groups. The FSFI subscale scores were significantly higher in the only-COVID group than in the long-COVID group for the Arousal, Lubrication, and Orgasm and lower for the Pain subscales and higher for overall sexual function (FSFI total Monly COVID = 27.49 [5.00] vs Mlong COVID = 25.77 [5.61]. None of the proposed mediation models had adequate model fit.

CLINICAL IMPLICATIONS: Clinicians treating cisgender women who have COVID-19 should consider proactively discussing sexual function with their patients and offering available resources.

STRENGTHS AND LIMITATIONS: In this study we used a large and diverse sample, but this sample did not include transgender or gender-diverse persons. This study was also correlational; as such, causal conclusions cannot be drawn. Further, the mechanism of action remains unexplained.

CONCLUSIONS: The study findings suggest the following: (1) COVID-19 infection is associated with impaired sexual function in cisgender women, and (2) that women with long COVID experienced incrementally more impaired sexual function than women with COVID-19 who did not develop long COVID.}, } @article {pmid38055113, year = {2024}, author = {Rayner, DG and Wang, E and Su, C and Patel, OD and Aleluya, S and Giglia, A and Zhu, E and Siddique, M}, title = {Risk factors for long COVID in children and adolescents: a systematic review and meta-analysis.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {2}, pages = {133-142}, pmid = {38055113}, issn = {1867-0687}, mesh = {Humans ; *COVID-19/epidemiology ; Child ; Risk Factors ; Adolescent ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized. This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population.

METHODS: We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses. Trial registries, reference lists of included studies, and preprint servers were hand-searched for relevant studies. Random-effects meta-analyses were conducted to pool odds ratios for each risk factor. Individual study risk of bias was rated using QUIPS, and the GRADE framework was used to assess the certainty of evidence for each unique factor.

RESULTS: Sixteen observational studies (N = 46,262) were included, and 19 risk factors were amenable to meta-analysis. With moderate certainty in the evidence, age (per 2-year increase), allergic rhinitis, obesity, previous respiratory diseases, hospitalization, severe acute COVID-19, and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID. Female sex, asthma, comorbidity, and heart diseases may be associated with an increased risk of long COVID, and Asian and Black races may be associated with a decreased risk of long COVID. We did not observe any credible subgroup effects for any risk factor.

CONCLUSIONS: The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population. Further research is necessary to elucidate the pathophysiology of long COVID.}, } @article {pmid38054902, year = {2023}, author = {Olteanu, GE and Pezzuto, F and Lunardi, F and Fortarezza, F and Dubini, A and Calabrese, F}, title = {Exploring the pathologist's role in understanding COVID-19: from pneumonia to long-COVID lung sequelae.}, journal = {Pathologica}, volume = {115}, number = {5}, pages = {275-283}, pmid = {38054902}, issn = {1591-951X}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Artificial Intelligence ; Pathologists ; SARS-CoV-2 ; *Pneumonia ; Lung/diagnostic imaging ; }, abstract = {The crucial role of pathologists in enhancing our understanding of SARS-CoV-2-related disease, from initial pneumonia manifestations to persistent long COVID lung symptoms, is the focus of this review. Pathological explorations have offered unprecedented insights into the early stages of severe COVID-19, shedding light on the interplay between the virus and subsequent complications, thereby shaping clinical approaches. Growing interest is directed to residual lung abnormalities of COVID-19 survivors. Although various radiological studies reported long-lasting pulmonary changes (e.g., ground glass opacities, reticulations, and bronchiectasis), the true incidence of pulmonary fibrosis and corresponding pathological findings in these patients remains largely unknown. There are a few high-impact and knowledgeable works on late complications in COVID-19 survivors, several coming from explant or autopsy cases, and rare cases from in vivo sampling. The study of biopsy samples has further deepened our knowledge of the aftermath of COVID-19 on lung tissue, uncovering alterations at the cellular level and shifts in vascular and epithelial dynamics. Despite the substantial progress made, future research is needed to devise a uniform strategy for interpreting lung biopsies, with a focus on leveraging advanced tools such as molecular and digital pathology techniques, along with artificial intelligence.}, } @article {pmid38054899, year = {2023}, author = {Chilosi, M and Doglioni, C and Ravaglia, C and Piciucchi, S and Dubini, A and Stefanizzi, L and Poletti, V}, title = {COVID-19. Biology, pathophysiology, and immunology: a pathologist view.}, journal = {Pathologica}, volume = {115}, number = {5}, pages = {248-256}, pmid = {38054899}, issn = {1591-951X}, mesh = {Humans ; *COVID-19 ; Pathologists ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biology ; }, abstract = {Even if the SARS-CoV-2 pandemic has been declared over, several risks and clinical problems remain to be faced, including long-COVID sequelae and possible outbreaks of pathogenic variants. Intense research on COVID-19 has provided in these few years a striking amount of data covering different fields and disciplines, which can help to provide a knowledge shield against new potential infective spreads, and may also potentially be applied to other fields of medicine, including oncology and neurology. Nevertheless, areas of uncertainty still remain regarding the pathogenic mechanisms that subtend the multifaceted manifestations of the disease. To better clarify the pathogenesis of the disease, a systematic multidisciplinary evaluation of the many mechanisms involved in COVID-19 is mandatory, including clinical, physiological, radiological, immunological and pathological studies. In COVID-19 syndrome the pathological studies have been mainly performed on autopsy cases, and only a few studies are available on biopsies. Nevertheless, these studies have provided relevant information that can substantially contribute to decipher the complex scenario characterizing the different forms of COVID-19 and long-COVID-19. In this review the data provided by pathological investigations are recapitulated and discussed, in the light of different hypothesis and data provided by clinical, physiological and immunological data.}, } @article {pmid38052015, year = {2024}, author = {Gwaikolo, C and Sackie-Wapoe, Y and Badio, M and Glidden, DV and Lindan, C and Martin, J}, title = {Prevalence and determinants of post-acute sequelae of COVID-19 in Liberia.}, journal = {International journal of epidemiology}, volume = {53}, number = {1}, pages = {}, pmid = {38052015}, issn = {1464-3685}, support = {R25 MH123256/MH/NIMH NIH HHS/United States ; U2R TW011281/TW/FIC NIH HHS/United States ; R25MH123256/MH/NIMH NIH HHS/United States ; 5U2RTW011281/GF/NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; *COVID-19/epidemiology ; Disease Progression ; Fatigue/epidemiology ; Liberia/epidemiology ; *Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Middle Aged ; }, abstract = {BACKGROUND: Evidence from resource-rich settings indicates that many people continue to have persistent symptoms following acute SARS-CoV-2 infection, called post-acute sequelae of COVID-19 (PASC). Only a few studies have described PASC in sub-Saharan Africa (SSA). We aimed to describe PASC in Liberia.

METHODS: We randomly sampled all people who were reported from the most populous county to the Liberian Ministry of Health (MOH) as having a laboratory-confirmed SARS-CoV-2 infection from June to August 2021. We interviewed individuals by phone 3 to 6 months later. Those with persistence of at least one symptom were considered to have PASC.

RESULTS: From among 2848 people reported to the MOH from Montserrado County during the period of interest, we randomly selected 650; of these, 548 (84.3%) were reached and 505 (92.2%) of those who were contacted were interviewed. The median age was 38 years (interquartile range (IQR), 30-49), and 43.6% were female. During acute infection, 40.2% were asymptomatic, 53.9% had mild/moderate disease and 6.9% had severe/critical disease. Among the 59.8% (n = 302) who were initially symptomatic, 50.2% (n = 152) reported at least one persistent symptom; the most common persistent symptoms were fatigue (21.2%), headache (16.2%) and cough (12.6%); 40.1% reported that PASC significantly affected their daily activities. Being hospitalized with moderate disease [adjusted prevalence ratio (aPR), 2.00 (95% CI, 1.59 to 2.80] or severe/critical disease [aPR, 2.11 (95% CI, 1.59 to 2.80)] was associated with PASC, compared with those not hospitalized. Females were more likely than males to report persistent fatigue [aPR, 1.67 (95% CI, 1.08 to 2.57)].

CONCLUSIONS: Our findings suggest that persistent symptoms may have affected a large proportion of people with initially symptomatic COVID-19 in west Africa and highlight the need to create awareness among infected people and health care professionals.}, } @article {pmid38045913, year = {2023}, author = {Jiang, Y and Cheng, Y and Xiao, J and Wang, Y and Chen, G and Zhang, Y}, title = {Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1273156}, pmid = {38045913}, issn = {2297-055X}, abstract = {OBJECTIVES: To analyze the correlation between heart rate variability (HRV) and palpitation symptoms in female patients with long COVID.

METHODS: A total of 272 female healthcare workers who were infected with SARS-CoV-2 for the first time in December 2022 at Fuzhou First Hospital affiliated with Fujian Medical University, were selected as study subjects. These subjects were divided into three groups based on their symptoms: a group with palpitations (70 cases), a group without palpitations but with other symptoms (124 cases), and a group consisting of asymptomatic cases (78 cases). The study compared the general information, COMPASS-31 scores, quality of life scores, and HRV parameters among the three groups. Furthermore, it analyzed the factors influencing palpitation symptoms in female patients with long COVID.

RESULTS: Compared to the other two groups, the HRV parameters SDNN, HRVIndex, LF, and TP were significantly reduced in the group with palpitations (p < 0.05). Multivariate analysis revealed that HRVIndex (p = 0.016; OR: 0.966, 95% CI: 0.940∼0.994) had a significant impact on palpitation symptoms in female patients with long COVID.

CONCLUSIONS: The symptoms of palpitations in female patients with long COVID were found to be related to HRV parameters. Autonomic dysfunction may be connected to the occurrence of palpitation symptoms in long COVID.}, } @article {pmid38045316, year = {2023}, author = {Aggarwal, A and Singh, TK and Pham, M and Godwin, M and Chen, R and McIntyre, TM and Scalise, A and Chung, MK and Jennings, C and Ali, M and Park, H and Englund, K and Khorana, AA and Svensson, LG and Kapadia, S and McCrae, KR and Cameron, SJ}, title = {Dysregulated Platelet Function in Patients with Post-Acute Sequelae of COVID-19.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.06.18.545507}, pmid = {38045316}, issn = {2692-8205}, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC), also referred as Long-COVID, sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, less is known about the thrombosis risk in PASC.

AIM: Our objective was to evaluate the platelet function and thrombotic potential in patients following recovery from SARS-CoV-2 with clear symptoms of PASC.

METHODS: PASC patients and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions.

RESULTS: A mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals.

CONCLUSIONS: PASC patients show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.}, } @article {pmid38044974, year = {2023}, author = {Allhaiby, NM and Allihybi, SM and Almhmadi, AH and Alkot, MM}, title = {Prevalence of long-lasting loss of smell and taste after coronavirus disease 2019 infection in Saudi Arabia.}, journal = {Journal of family & community medicine}, volume = {30}, number = {4}, pages = {295-299}, pmid = {38044974}, issn = {1319-1683}, abstract = {BACKGROUND: People with coronavirus disease 2019 (COVID-19) who experience symptoms for more than 35 weeks are said to have long COVID. Anosmia can occur on its own or in combination with other COVID-19 symptoms. Anosmia may be a significant differential presentation for the suspicion and diagnosis of COVID-19 in patients with asymptomatic-to-mild COVID-19 disease and may disappear in 3 weeks. This study sought to determine the prevalence of persistent loss of taste and smell following COVID-19 in Saudi Arabia.

MATERIALS AND METHODS: A population-based cross-sectional study was conducted among Saudi citizens who had been diagnosed with COVID-19 for more than 2 weeks and had experienced a loss of taste and smell. Data was collected using a questionnaire having questions about demographics, long-lasting loss of taste and smell, whether this related to COVID-19 infection, and whether respondents had received the COVID-19 vaccine. SPSS was used for data analysis; statistical significance was determined using Chi-square test.

RESULTS: A total of 383 Saudis who had a history of COVID-19 participated in the study. About 43.3% study participants had experienced persistent loss of taste and smell after COVID-19 infection. A significant association was found between loss of smell and the region, Northern region having highest proportion of study participants who had loss of smell and Western region having the lowest prevalence (34%).

CONCLUSION: There were permanent changes in the sense of taste or smell in 34.3% of participants. This might add to the growing weight of long COVID.}, } @article {pmid38043758, year = {2024}, author = {Kitselman A, K and Bédard-Matteau, J and Rousseau, S and Tabrizchi, R and Daneshtalab, N}, title = {Sex differences in vascular endothelial function related to acute and long COVID-19.}, journal = {Vascular pharmacology}, volume = {154}, number = {}, pages = {107250}, doi = {10.1016/j.vph.2023.107250}, pmid = {38043758}, issn = {1879-3649}, mesh = {Humans ; Female ; Male ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/epidemiology ; Sex Characteristics ; *Vascular Diseases ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction. There were also some noted differences in the rate and severity of infection between males and females with acute COVID. Some individuals infected with SARS-CoV-2 also experience long-COVID, an important hallmark symptom of this being Myalgic Encephalomyelitis-Chronic Fatigue Syndrome (ME-CFS), also experienced differently between males and females. The purpose of this review is to discuss the impact of sex on the vasculature during acute and long COVID-19, present any link between ME-CFS and endothelial dysfunction, and provide evidence for the relationship between ME-CFS and the immune system. We also will delineate biological sex differences observed in other post viral infections and, assess if sex differences exist in how the immune system responds to viral infection causing ME-CFS.}, } @article {pmid38041762, year = {2024}, author = {Kuchler, T and Hausinger, R and Braunisch, MC and Günthner, R and Wicklein, R and Knier, B and Bleidißel, N and Maier, M and Ribero, A and Lech, M and Adorjan, K and Stubbe, H and Kotilar, K and Heemann, U and Schmaderer, C}, title = {All eyes on PCS: analysis of the retinal microvasculature in patients with post-COVID syndrome-study protocol of a 1 year prospective case-control study.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1847-1856}, pmid = {38041762}, issn = {1433-8491}, support = {H.4001.1.7-53/7//Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; *COVID-19/complications/physiopathology ; *Microvessels/diagnostic imaging/physiopathology/pathology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *Retinal Vessels/diagnostic imaging/physiopathology/pathology ; Tomography, Optical Coherence ; Observational Studies as Topic ; Research Design ; }, abstract = {Since widespread vaccination against COVID-19, the development of effective antiviral drugs, and the decreasing number of patients with COVID-19 in intensive care, the risk from SARS-CoV-2 infection appears less threatening. However, studies show that a significant number of patients suffer from long-term sequelae, even months after SARS-CoV-2 infection. The so-called post-COVID syndrome (PCS) often presents a diagnostic and treatment challenge for physicians. This study protocol describes the "All Eyes on PCS" study, which aims to investigate the retinal microvasculature in PCS patients and COVID-19-recovered patients to provide new insights into the pathophysiology of PCS. "All Eyes on PCS" is a prospective, case-control study with the primary objective of detecting endothelial dysfunction (ED) in patients with PCS. Therefore, we intend to recruit patients with PCS, fully SARS-CoV-2-infection-recovered (CR) participants, and SARS-CoV-2-infection-naïve (CN) participants. Baseline measurements will include: (1) patient-specific characteristics, (2) biochemistry, (3) retinal vessel analysis (RVA), (4) survey questionnaires as patient-reported outcomes measurements (PROMs), (5) optical coherence tomography (OCT), OCT angiography (OCTA), and adaptive optics (AO), (6) blood pressure recordings, (7) handgrip strength test. After 6 months, baseline measurements will be repeated in the PCS cohort, and after 1 year, a telephone query will be conducted to assess residual symptoms and treatment needs. The aim of this study is to gain insight into the pathophysiology of PCS and to provide an objective biomarker for diagnosis and treatment, while also creating a comprehensive clinical database of PCS patients.ClinicalTrials.gov Identifier: NCT05635552; Date: 2.12.2022.}, } @article {pmid38039619, year = {2024}, author = {Montserrat-Capdevila, J and Fornells-Barberà, I and Roso-Llorach, A and Olivares-Sanzo, P and Romero-Gracia, A and Ichart, JX}, title = {[Impact of COVID-19 on the mental health of the population: Study in primary care].}, journal = {Atencion primaria}, volume = {56}, number = {3}, pages = {102813}, pmid = {38039619}, issn = {1578-1275}, mesh = {Humans ; Female ; Aged ; Male ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Case-Control Studies ; Primary Health Care ; }, abstract = {OBJECTIVE: To determine the prevalence of COVID-19 and the characteristics of infected patients, as well as the prevalence of mental disorders associated with the infection and the associated risk factors. Secondary: to know the prevalence of the long COVID syndrome and the characteristics of this cohort.

DESIGN: Incidence study of mental disorder in patients diagnosed with COVID-19 and case-control study of long COVID syndrome in the subsample of patients diagnosed with COVID-19 without a history of mental disorder. SITE: Primary care setting in Lleida.

PARTICIPANTS: The 46,258 patients diagnosed of COVID-19 without a history of mental disorder were followed for 2 years.

MAIN MEASUREMENTS: The dependent variable was the mental disorder in the period 03/11/2020 to 03/11/2022; and the independent variables were clinical and social variables. Its association with mental disorder was analyzed by calculating the adjusted hazard ratio using a logistic regression model.

RESULTS: The average age of 46,258 patients at the beginning of the study was 43±17.9 years. 47% were women. The mental disorder rate for all period was 3.46% (59.20% anxiety). A predictive score was elaborated. The long COVID syndrome was more common in older women, without toxic habits, with obesity and associated comorbidity.

CONCLUSIONS: COVID-19 has had an impact on the mental health of patients. Knowing the risk factors for developing these mental disorders and the long COVID syndrome would allow the clinician to be able to identify patients at risk in order to establish preventive measures and avoid their appearance.}, } @article {pmid38037477, year = {2023}, author = {Turk, F and Sweetman, J and Allsopp, G and Crooks, M and Cuthbertson, DJ and Gabbay, M and Hishmeh, L and Lip, GYH and Strain, WD and Williams, N and Wootton, D and Banerjee, A and van der Feltz-Cornelis, C and , }, title = {Pathways to care for Long COVID and for long-term conditions from patients' and clinicians' perspective.}, journal = {Journal of evidence-based medicine}, volume = {16}, number = {4}, pages = {435-437}, doi = {10.1111/jebm.12563}, pmid = {38037477}, issn = {1756-5391}, support = {COV-LT2-0043//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Attitude of Health Personnel ; }, } @article {pmid38036708, year = {2024}, author = {Lewis, S}, title = {The long COVID haul.}, journal = {Nature reviews. Neuroscience}, volume = {25}, number = {1}, pages = {4}, pmid = {38036708}, issn = {1471-0048}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid38036541, year = {2023}, author = {Hastie, CE and Lowe, DJ and McAuley, A and Mills, NL and Winter, AJ and Black, C and Scott, JT and O'Donnell, CA and Blane, DN and Browne, S and Ibbotson, TR and Pell, JP}, title = {True prevalence of long-COVID in a nationwide, population cohort study.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7892}, pmid = {38036541}, issn = {2041-1723}, support = {CH/F/21/90010/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Prevalence ; }, abstract = {Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.}, } @article {pmid38036270, year = {2024}, author = {Besteher, B and Rocktäschel, T and Garza, AP and Machnik, M and Ballez, J and Helbing, DL and Finke, K and Reuken, P and Güllmar, D and Gaser, C and Walter, M and Opel, N and Rita Dunay, I}, title = {Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment.}, journal = {Brain, behavior, and immunity}, volume = {116}, number = {}, pages = {175-184}, doi = {10.1016/j.bbi.2023.11.028}, pmid = {38036270}, issn = {1090-2139}, mesh = {Humans ; Cerebral Cortex/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Cognitive Dysfunction ; Brain/diagnostic imaging ; Magnetic Resonance Imaging ; }, abstract = {As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients. To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3 T-MRI scans and signature inflammatory markers in n = 120 participants comprising healthy never-infected controls (n = 30), healthy COVID-19 survivors (n = 29), and subgroups of long-COVID patients with (n = 26) and without (n = 35) cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p < 0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment. We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.}, } @article {pmid38034398, year = {2023}, author = {Wu, F and Lin, C and Han, Y and Zhou, D and Chen, K and Yang, M and Xiao, Q and Zhang, H and Li, W}, title = {Multi-omic analysis characterizes molecular susceptibility of receptors to SARS-CoV-2 spike protein.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5583-5600}, pmid = {38034398}, issn = {2001-0370}, abstract = {In the post COVID-19 era, new SARS-CoV-2 variant strains may continue emerging and long COVID is poised to be another public health challenge. Deciphering the molecular susceptibility of receptors to SARS-CoV-2 spike protein is critical for understanding the immune responses in COVID-19 and the rationale of multi-organ injuries. Currently, such systematic exploration remains limited. Here, we conduct multi-omic analysis of protein binding affinities, transcriptomic expressions, and single-cell atlases to characterize the molecular susceptibility of receptors to SARS-CoV-2 spike protein. Initial affinity analysis explains the domination of delta and omicron variants and demonstrates the strongest affinities between BSG (CD147) receptor and most variants. Further transcriptomic data analysis on 4100 experimental samples and single-cell atlases of 1.4 million cells suggest the potential involvement of BSG in multi-organ injuries and long COVID, and explain the high prevalence of COVID-19 in elders as well as the different risks for patients with underlying diseases. Correlation analysis validated moderate associations between BSG and viral RNA abundance in multiple cell types. Moreover, similar patterns were observed in primates and validated in proteomic expressions. Overall, our findings implicate important therapeutic targets for the development of receptor-specific vaccines and drugs for COVID-19.}, } @article {pmid38033805, year = {2023}, author = {Kim, SE}, title = {Long COVID Researchers Are on the Hunt for Causes and Cures.}, journal = {ACS central science}, volume = {9}, number = {11}, pages = {1996-2001}, doi = {10.1021/acscentsci.3c01331}, pmid = {38033805}, issn = {2374-7943}, } @article {pmid38033774, year = {2023}, author = {Kim, SA and Lee, JS and Kim, T and Kim, TH and Kwon, S and Kang, JW}, title = {Efficacy and safety of acupuncture treatment for fatigue after COVID-19 infection: study protocol for a pilot randomized sham-controlled trial.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1302793}, pmid = {38033774}, issn = {1664-2295}, abstract = {BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic has spread globally, its sequelae, called Long COVID, have persisted, troubling patients worldwide. Although fatigue is known to be the most frequent among Long COVID symptoms, its mechanism and treatment have not been clearly demonstrated. In 2022, we conducted a preliminary prospective case series and found that acupuncture and moxibustion were feasible interventions for fatigue. This study is a pilot patient-assessor-blinded randomized sham-controlled trial to evaluate the efficacy and safety of acupuncture treatment for patients with fatigue that has persisted for at least 4 weeks after recovery from COVID-19.

METHODS: Thirty patients will be recruited and randomly assigned to either the acupuncture or sham acupuncture treatment groups. Treatment will be conducted thrice a week for both groups during 4 weeks. The primary outcome will be the efficacy and safety of acupuncture, including numeric rating scale (NRS), brief fatigue inventory (BFI), fatigue severity scale (FSS), and adverse event evaluation. Secondary outcomes will be evaluation of improvement in the comorbid symptoms of fatigue and feasibility variables. Outcome variables will be assessed before treatment, 4 weeks after treatment, and 8 weeks after treatment completion.

DISCUSSION: The results of this study will be used to clarify the efficacy and safety of acupuncture treatment for persistent fatigue in patients with Long COVID. Additionally, the feasibility of the study design was validated to provide evidence for future full-scale randomized controlled trials.Clinical trial registration: identifier: KCT0008656 https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24785&search_page=L.}, } @article {pmid38033705, year = {2023}, author = {Avula, N and Kakach, D and Tignanelli, CJ and Liebovitz, DM and Nicklas, JM and Cohen, K and Puskarich, MA and Belani, HK and Buse, JB and Klatt, NR and Anderson, B and Karger, AB and Hartman, KM and Patel, B and Fenno, SL and Reddy, NV and Erickson, SM and Boulware, DR and Murray, TA and Bramante, CT and , }, title = {Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2.}, journal = {Journal of clinical and translational science}, volume = {7}, number = {1}, pages = {e242}, pmid = {38033705}, issn = {2059-8661}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; P30 DK124723/DK/NIDDK NIH HHS/United States ; }, abstract = {The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT's are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.}, } @article {pmid38029227, year = {2023}, author = {Bellone, S and Siegel, EE and Santin, AD}, title = {Increased serum 1,25-dihydroxyvitamin D levels in gynecologic cancer patients with Post-Acute-Covid-Sequela (PASC)/Long COVID.}, journal = {Gynecologic oncology reports}, volume = {50}, number = {}, pages = {101301}, pmid = {38029227}, issn = {2352-5789}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {Post-acute sequelae of COVID-19 (PASC), also known as Long-Covid (LC), may affect 10-30 % of COVID-infected patients, and is characterized by a variety of debilitating symptoms lasting over 3 months after the acute infection, including but not limited to dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. Vitamin D is an essential nutrient primarily recognized for its role in regulating calcium and bone health but also endowed with potent anti-inflammatory activity affecting a variety of immune cells. We retrospectively evaluated the plasmatic levels of both 1,25-dihydroxyvitamin-D (1,25 OH), and 25-hydroxyvitamin-D (25 OH), the active and storage forms of vitamin-D3, respectively, in the serum of gynecologic cancer patients affected by PASC/LC vs control cancer patients. We found elevated 1,25-dihydroxyvitamin-D levels in 5 out of 5 of the PASC/LC patients (mean ± SD = 97.2 ± 26.9 pg/mL) versus 0 out of 10 of randomly selected cancer control patients (44.9 ± 17.2 pg/mL, p = 0.0005). In contrast, no significant difference was noted in the levels of 25-dihydroxyvitamin-D in PASC/LC (mean ± SD = 48.2 ± 15.8 ng/mL) versus controls (43.0 ± 11.6 ng/mL, p = 0.48). Importantly, abnormal levels of vitamin D were found to persist for at least 2 years in patients with long covid symptoms. The active form (1,25OH) but not the storage form (25 OH) of vitamin-D is significantly elevated in PASC/LC cancer patients. Abnormally and persistently elevated 1,25OH levels, similarly to sarcoidosis patients, may represent the results of extrarenal conversion of vitamin D by activated macrophages, and a novel biomarker of persistent inflammation in gynecologic cancer patients with PASC/LC.}, } @article {pmid38028898, year = {2023}, author = {Marra, AR and Kobayashi, T and Callado, GY and Pardo, I and Gutfreund, MC and Hsieh, MK and Lin, V and Alsuhaibani, M and Hasegawa, S and Tholany, J and Perencevich, EN and Salinas, JL and Edmond, MB and Rizzo, LV}, title = {The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research.}, journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE}, volume = {3}, number = {1}, pages = {e168}, pmid = {38028898}, issn = {2732-494X}, abstract = {OBJECTIVE: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) among fully vaccinated individuals.

DESIGN: Systematic literature review/meta-analysis.

METHODS: We searched PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to June 2, 2023, for studies evaluating the COVID-19 vaccine effectiveness (VE) against post-COVID conditions among fully vaccinated individuals who received two doses of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present four or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% confidence interval) for post-COVID conditions between fully vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% x (1-DOR).

RESULTS: Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR for post-COVID conditions among fully vaccinated individuals was 0.680 (95% CI: 0.523-0.885) with an estimated VE of 32.0% (11.5%-47.7%). Vaccine effectiveness was 36.9% (23.1%-48.2%) among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% (64.7%-72.2%) among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection.

CONCLUSIONS: Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.}, } @article {pmid38028346, year = {2023}, author = {Kotarba, JA and Molldrem, S and Smith, E and Spratt, H and Bhavnani, SK and Farroni, JS and Wooten, K}, title = {Exploring team dynamics during the development of a multi-institutional cross-disciplinary translational team: Implications for potential best practices.}, journal = {Journal of clinical and translational science}, volume = {7}, number = {1}, pages = {e220}, pmid = {38028346}, issn = {2059-8661}, support = {UL1 TR001439/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: A recent literature review revealed no studies that explored teams that used an explicit theoretical framework for multiteam systems in academic settings, such as the increasingly important multi-institutional cross-disciplinary translational team (MCTT) form. We conducted an exploratory 30-interview grounded theory study over two rounds to analyze participants' experiences from three universities who assembled an MCTT in order to pursue a complex grant proposal related to research on post-acute sequelae of COVID-19, also called "long COVID." This article considers activities beginning with preliminary discussions among principal investigators through grant writing and submission, and completion of reviews by the National Center for Advancing Translational Sciences, which resulted in the proposal not being scored.

METHODS: There were two stages to this interview study with MCTT members: pre-submission, and post-decision. Round one focused on the process of developing structures to collaborate on proposal writing and assembly, whereas round two focused on evaluation of the complete process. A total of 15 participants agreed to be interviewed in each round.

FINDINGS: The first round of interviews was conducted prior to submission and explored issues during proposal writing, including (1) importance of the topic; (2) meaning and perception of "team" within the MCTT context; and (3) leadership at different levels of the team. The second round explored best practices-related issues including (1) leadership and design; (2) specific proposal assembly tasks; (3) communication; and (4) critical events.

CONCLUSION: We conclude with suggestions for developing best practices for assembling MCTTs involving multi-institutional teams.}, } @article {pmid38028335, year = {2023}, author = {Dulko, D and Kwong, M and Palm, ME and Trinquart, L and Selker, HP}, title = {From a decentralized clinical trial to a decentralized and clinical-trial-in-a-box platform: Towards patient-centric and equitable trials.}, journal = {Journal of clinical and translational science}, volume = {7}, number = {1}, pages = {e236}, pmid = {38028335}, issn = {2059-8661}, abstract = {BACKGROUND/OBJECTIVE: Despite the intuitive attractiveness of bringing research to participants rather than making them come to central study sites, widespread decentralized enrollment has not been common in clinical trials.

METHODS: The need for clinical research in the context of the COVID-19 pandemic, along with innovations in technology, led us to use a decentralized trial approach in our Phase 2 COVID-19 trial. We used real-time acquisition and transmission of health-related data using home-based monitoring devices and mobile applications to assess outcomes. This approach not only avoids spreading COVID-19 but it also can support inclusion of participants in more diverse socioeconomic circumstances and in rural settings.

RESULTS: Our team developed and deployed a decentralized trial platform to support patient engagement and adverse event reporting. Clinicians, engineers, and informaticians on our research team developed a Clinical-Trial-in-a-Box tool to optimally collect and analyze data from multiple decentralized platforms.

CONCLUSION: Applying the decentralized model in Long COVID, using digital health technology and personal devices integrated with our telehealth platform, we share the lessons learned from our work, along with challenges and future possibilities.}, } @article {pmid38028066, year = {2023}, author = {Stewart, DD}, title = {Can Nitazoxanide and/or other anti-viral medications be a solution to long COVID? Case report with a brief literature review.}, journal = {Clinical case reports}, volume = {11}, number = {11}, pages = {e8162}, pmid = {38028066}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: Findings here imply lingering of virus, SARS-CoV-2, in the body for months. Thus, Nitazoxanide and/or other anti-viral medications might be potential options to combat long COVID. This could transform treatment for long COVID patients globally.

ABSTRACT: Long COVID or post-acute sequelae of COVID-19 (PASC) continues to affect many people even after a relatively mild acute illness. Underlying causes of PASC are poorly understood. There is no particular treatment or management program developed yet. Thus, the possibility of well-known, safe anti-viral medications use against PASC is proposed here.}, } @article {pmid38026427, year = {2023}, author = {Grabowska, AD and Westermeier, F and Nacul, L and Lacerda, E and Sepúlveda, N}, title = {The importance of estimating prevalence of ME/CFS in future epidemiological studies of long COVID.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1275827}, pmid = {38026427}, issn = {2296-2565}, support = {R01 AI170839/AI/NIAID NIH HHS/United States ; R01 AI170839/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19/epidemiology ; Epidemiologic Studies ; }, } @article {pmid38026381, year = {2023}, author = {, }, title = {Retraction: Post-acute (long) COVID-19 quality of life: validation of the German version of (PAC19QoL) instrument.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1308285}, doi = {10.3389/fpubh.2023.1308285}, pmid = {38026381}, issn = {2296-2565}, abstract = {[This retracts the article DOI: 10.3389/fpubh.2023.1163360.].}, } @article {pmid38026271, year = {2023}, author = {Ahmad, I and Merla, A and Ali, F and Shah, B and AlZubi, AA and AlZubi, MA}, title = {A deep transfer learning approach for COVID-19 detection and exploring a sense of belonging with Diabetes.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1308404}, pmid = {38026271}, issn = {2296-2565}, mesh = {Humans ; Aged ; *COVID-19/diagnosis ; *Diabetes Mellitus/diagnosis/epidemiology ; *Hyperglycemia ; *Pneumonia, Viral ; Machine Learning ; }, abstract = {COVID-19 is an epidemic disease that results in death and significantly affects the older adult and those afflicted with chronic medical conditions. Diabetes medication and high blood glucose levels are significant predictors of COVID-19-related death or disease severity. Diabetic individuals, particularly those with preexisting comorbidities or geriatric patients, are at a higher risk of COVID-19 infection, including hospitalization, ICU admission, and death, than those without Diabetes. Everyone's lives have been significantly changed due to the COVID-19 outbreak. Identifying patients infected with COVID-19 in a timely manner is critical to overcoming this challenge. The Real-Time Polymerase Chain Reaction (RT-PCR) diagnostic assay is currently the gold standard for COVID-19 detection. However, RT-PCR is a time-consuming and costly technique requiring a lab kit that is difficult to get in crises and epidemics. This work suggests the CIDICXR-Net50 model, a ResNet-50-based Transfer Learning (TL) method for COVID-19 detection via Chest X-ray (CXR) image classification. The presented model is developed by substituting the final ResNet-50 classifier layer with a new classification head. The model is trained on 3,923 chest X-ray images comprising a substantial dataset of 1,360 viral pneumonia, 1,363 normal, and 1,200 COVID-19 CXR images. The proposed model's performance is evaluated in contrast to the results of six other innovative pre-trained models. The proposed CIDICXR-Net50 model attained 99.11% accuracy on the provided dataset while maintaining 99.15% precision and recall. This study also explores potential relationships between COVID-19 and Diabetes.}, } @article {pmid38025798, year = {2023}, author = {Wang, JJ and Zhang, QF and Liu, D and Du, Q and Xu, C and Wu, QX and Tang, Y and Jin, WS}, title = {Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.}, journal = {Journal of Alzheimer's disease reports}, volume = {7}, number = {1}, pages = {1127-1132}, pmid = {38025798}, issn = {2542-4823}, abstract = {BACKGROUND: The acute stage of COVID-19 often presents with neurological manifestations.

OBJECTIVE: This study aims to investigate the long-term neurological effects on survivors.

METHODS: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19.

RESULTS: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms.

CONCLUSION: Neurological symptoms are common among COVID-19 survivors, especially in severe cases.}, } @article {pmid38025440, year = {2023}, author = {Perea-Flórez, F and Javier-Murillo, N and Lapeyre-Rivera, A and Gamonal, B and Cabanillas-Lazo, M and Velásquez-Rimachi, V and Alva-Diaz, C}, title = {Prevalence and incidence of neuropsychiatric disorders in post hospitalized COVID-19 patients in South America: a systematic review and meta-analysis.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1163989}, pmid = {38025440}, issn = {1664-0640}, abstract = {INTRODUCTION: There are multiple reports of neuropsychiatric disorders (NDs) such as stress, depression, post-traumatic stress disorder (PTSD), or anxiety, in patients who have survived the acute phase of COVID-19, being even more frequent in people who were hospitalized with moderate or severe disease. South America (SA) was one of the most affected continents during this time due to its health, social, political and economic context. We aimed to determine the prevalence and incidence of NDs in patients following hospitalization for COVID-19 in SA.

MATERIALS AND METHODS: We searched in PubMed, Embase, Scopus, Web of Science, LILACS, SciELO, and Google Scholar databases up to October 2022. We performed proportion meta-analysis with a random-effect model and Freeman-Tukey Double Arcsine transformation using the STATA 16.1 program. Finally, we evaluated heterogeneity by subgroup analysis and certainty of evidence with the GRADE approach.

RESULTS: We included eight studies from four countries. We only pooled six studies with prevalence measures. The estimated prevalence of all NDs was 31.48% (two-studies, 95%CI: 25.82-37.43). Depression, anxiety, insomnia, PTSD, and memory alterations had a pooled prevalence of 16.23% (three-studies, 95%CI: 7.18-27.93, I2: 94.22), 18.72% (three-studies, 95%CI: 11.65-26.97, I2: 87.56), 43.07% (three-studies, 95%CI: 32.77-53.37, I2: 92.61), 31.78% (three-studies, 95%CI: 14.33-52.40, I2: 97.96), and 38.24% (two-studies, 95%CI: 35.5-40.97), respectively. The evidence included was deemed as moderate to high certainty.

CONCLUSION: We suggest that NDs should be prioritized in research and care in South America with public policies that can support their identification and prompt management to improve the quality of life of patients. More studies are needed to adequately study the prevalence of NDs in South America, their associated factors, and evaluate the causes of heterogeneity.

https://doi.org/10.6084/m9.figshare.21901041.v1.}, } @article {pmid38025401, year = {2023}, author = {Fonseca, BHS and de Andrade, PHS and Henrique, MESA and Baggio, JAO and Bazan, R and de Souza, LAPS and Luvizutto, GJ}, title = {Perception of verticality in the post-COVID-19 condition correlates to infection severity.}, journal = {Journal of central nervous system disease}, volume = {15}, number = {}, pages = {11795735231195693}, pmid = {38025401}, issn = {1179-5735}, abstract = {BACKGROUND: SARS-CoV-2 infection affects multiple systems, including musculoskeletal, neurological, and respiratory systems. Changes associated with physical inactivity due to prolonged hospitalization can affect the functional capacity of individuals with long coronavirus disease 2019 (COVID-19) or post-COVID-19 condition and may cause changes in some postural control functions, such as verticality.

OBJECTIVES: This study aimed to evaluate the perception of verticality in individuals with long COVID.

DESIGN: Cross-sectional study.

METHODS: This study included 60 participants with post-COVID-19 condition divided into 2 groups: hospitalized group (n = 24), those hospitalized owing to SARS-CoV-2 infection; and non-hospitalized group (n = 36), those infected with SARS-CoV-2 but not hospitalized. All participants were examined using a post-COVID-19 functional status (PCFS), sit-to-stand test, grip strength assessment, painful and tactile sensory assessments, visual acuity assessment, and vestibular assessment. Verticality perception was evaluated using the subjective visual vertical (SVV) and subjective haptic vertical (SHV) tests. In both tests, the absolute values (positive values only) and true values (positive and negative values) were considered. To verify potential confounders that could influence the verticality of the results, logistic regression models were used for categorical variables and multiple linear regressions were used for continuous variables. For analysis between groups, the independent samples test (Mann-Whitney U test) was used.

RESULTS: There were no confounders between clinical variables and verticality in either group. There was a significant increase in absolute SVV (mean deviation [MD]: 2.83; P < .0001) and true SVV (MD: -4.18; P = .005) in the hospitalized group compared to the non-hospitalized group. Furthermore, there was a significant increase in the true SHV (MD: -3.6; P = .026) in the hospitalized group compared to that in the non-hospitalized group.

CONCLUSION: Less accurate visual and haptic verticality perception task performance was observed in hospitalized patients with post-COVID-19 condition.}, } @article {pmid38024352, year = {2023}, author = {Grundler, F and Mesnage, R and Cerrada, A and Wilhelmi de Toledo, F}, title = {Improvements during long-term fasting in patients with long COVID - a case series and literature review.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1195270}, pmid = {38024352}, issn = {2296-861X}, abstract = {BACKGROUND: Post-acute sequelae of a severe acute respiratory syndrome coronavirus 2 infection, also known as long COVID, comprises a variety of symptoms that impair the quality of life. This represents a growing public health burden, with millions of individuals worldwide affected.

CASE DESCRIPTION: We present a case series of 14 COVID-19 patients with post-acute symptoms who underwent medically supervised long-term fasting (6 to 16 days) according to the peer-reviewed Buchinger Wilhelmi protocol. The EQ-5D-5L questionnaire and visual scales were used to evaluate the intensity of the symptoms, retrospectively during the acute phase, and prospectively before and after long-term fasting. Blood tests were also performed before and after fasting. Thirteen patients reported that fasting caused an enhancement in their perceived overall health. Only one patient had no improvement. Both frequent (fatigue, breathlessness, muscle and joint pains) and less frequent (cognitive impairment, smell and taste disorders) sequelae ameliorated. Body weight and other risk factors for cardiometabolic diseases like blood pressure, blood glucose, total cholesterol, low-density-lipoprotein cholesterol, and triglycerides were reduced. No severe side effects occurred.

DISCUSSION: This case series reports beneficial changes in self-perceived symptoms in patients with long COVID after long-term fasting. This highlights the potential of long-term fasting as an effective intervention for managing and treating long COVID.}, } @article {pmid38024037, year = {2023}, author = {Hulscher, N and Procter, BC and Wynn, C and McCullough, PA}, title = {Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49204}, pmid = {38024037}, issn = {2168-8184}, abstract = {The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term post-infection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of post-acute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.}, } @article {pmid38023981, year = {2023}, author = {Romero, M and Caicedo, M and Díaz, A and Ortega, D and Llanos, C and Concha, A and Vallejo, A and Valdés, F and González, C}, title = {Post-COVID-19 syndrome: Descriptive analysis based on a survivors' cohort in Colombia.}, journal = {Global epidemiology}, volume = {6}, number = {}, pages = {100126}, pmid = {38023981}, issn = {2590-1133}, abstract = {BACKGROUND: The prevalence of post-COVID-19 Syndrome (PCS) is estimated to be between 10% and 20%. The main reported symptoms are fatigue, memory alterations, dyspnea, sleep disorders, arthralgia, anxiety, taste alterations, coughing and depression. This study aims to determine the prevalence of post-COVID-19 symptoms in a group of Colombian patients who were recruited during their outpatient appointments.

METHODOLOGY: This cross-sectional study was conducted between December 2021 to May 2022. It included patients from outpatient facilities located in five main cities in Colombia who were positive for SARS-CoV-2 infection detected by reverse transcription-polymerase chain reaction (RT-PCR) testing and reported PCS in the following 12 weeks after their COVID-19 diagnosis.

RESULTS: A total of 1047 individuals >18 years old met the inclusion criteria and were included in the study. The median age was 46 years old. 68.2% of the participants were female, 41.5% of the patients reported having a pre-existent condition (hypertension, anxiety disorder, diabetes, hyperthyroidism, obesity and asthma). Only 22% had received at least one dose of COVID-19 vaccine prior to the COVID-19 episode registered. The more prevalent symptoms within our group are described as follows: fatigue (53.3%), dyspnea (40.3%), arthralgia and/or myalgia (43%), cephalea (40.5%), sleep disorders (35.7%) and coughing (31.3%). 72% of the patients presented four or more post-COVID 19 symptoms, 9% two symptoms, and 10% only one symptom.

CONCLUSION: The findings of this study are consistent with international literature publicly available. The distribution and prevalence of post-COVID symptoms highlight the importance of further research to improve understanding and its potential consequences and implications in terms of quality of life and health care planning services.}, } @article {pmid38023955, year = {2023}, author = {Bîrluţiu, V and Bîrluţiu, RM and Feiereisz, AI and Dobriţoiu, ES}, title = {Facial palsy at the onset of SARS-CoV-2 infection. A case report.}, journal = {Germs}, volume = {13}, number = {1}, pages = {65-71}, pmid = {38023955}, issn = {2248-2997}, abstract = {INTRODUCTION: SARS-CoV-2 infection has been associated with an increased number of deaths, due to severe respiratory damage, cardiovascular impairment, acute renal failure, and also neurological injury, including stroke, which is most commonly responsible for death. These are elements that determine patients to seek medical advice.

CASE REPORT: This is a case report of a female Caucasian patient, aged 65 years, with type 2 diabetes mellitus on metformin 1000 mg twice/day, and hypertension, who presented to the emergency department with one day history of left orbital hyperlacrimation and chewing and swallowing difficulty. On physical examination there was a decreased blink reflex, flattened nasolabial fold, and drooping left corner of the mouth, with left conjunctival hyperemia, and a present corneal reflex. Motion limited head CT and MRI revealed no pathological changes suggestive for the appearance of paresis. The patient was transferred to the Department of Infectious Diseases after laboratory confirmation of SARS-CoV-2 infection. Under treatment, improvement of paresis after three days was observed, with minimal asymmetry left five days after admission. A reassessment one month after discharge revealed complete recovery of the paresis, physical asthenia, and headache, in the context of long-COVID syndrome.

CONCLUSIONS: The appearance of paresis may be a consequence of the direct action of the virus on the nervous system, of hypercoagulability, or, later, of an immune mechanism. The case presented is judged as an early, direct action of the virus on the central nervous system, the respiratory symptoms were minimized by the patient at the time of presentation.}, } @article {pmid38021227, year = {2023}, author = {Fernández-de-Las-Peñas, C and Cancela-Cilleruelo, I and Rodríguez-Jiménez, J and Arias-Navalón, JA and Martín-Guerrero, JD and Pellicer-Valero, OJ and Arendt-Nielsen, L and Cigarán-Méndez, M}, title = {Trajectory of post-COVID brain fog, memory loss, and concentration loss in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study.}, journal = {Frontiers in human neuroscience}, volume = {17}, number = {}, pages = {1259660}, pmid = {38021227}, issn = {1662-5161}, abstract = {OBJECTIVE: This study aimed to apply Sankey plots and exponential bar plots for visualizing the trajectory of post-COVID brain fog, memory loss, and concentration loss in a cohort of previously hospitalized COVID-19 survivors.

METHODS: A sample of 1,266 previously hospitalized patients due to COVID-19 during the first wave of the pandemic were assessed at 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of the following self-reported cognitive symptoms: brain fog (defined as self-perception of sluggish or fuzzy thinking), memory loss (defined as self-perception of unusual forgetfulness), and concentration loss (defined as self-perception of not being able to maintain attention). We asked about symptoms that individuals had not experienced previously, and they attributed them to the acute infection. Clinical and hospitalization data were collected from hospital medical records.

RESULTS: The Sankey plots revealed that the prevalence of post-COVID brain fog was 8.37% (n = 106) at T1, 4.7% (n = 60) at T2, and 5.1% (n = 65) at T3, whereas the prevalence of post-COVID memory loss was 14.9% (n = 189) at T1, 11.4% (n = 145) at T2, and 12.12% (n = 154) at T3. Finally, the prevalence of post-COVID concentration loss decreased from 6.86% (n = 87) at T1, to 4.78% (n = 60) at T2, and to 2.63% (n = 33) at T3. The recovery exponential curves show a decreasing trend, indicating that these post-COVID cognitive symptoms recovered in the following years after discharge. The regression models did not reveal any medical record data associated with post-COVID brain fog, memory loss, or concentration loss in the long term.

CONCLUSION: The use of Sankey plots shows a fluctuating evolution of post-COVID brain fog, memory loss, or concentration loss during the first years after the infection. In addition, exponential bar plots revealed a decrease in the prevalence of these symptoms during the first years after hospital discharge. No risk factors were identified in this cohort.}, } @article {pmid38020953, year = {2023}, author = {Carpio-Orantes, LD and Aguilar-Silva, A and García-Méndez, S and Sánchez-Diaz, JS and Rodríguez-Contreras, Y and Lara-Hernández, E and Fernández-Márquez, D}, title = {Neuropsychiatric manifestations in patients with long COVID in Mexico.}, journal = {Brain circulation}, volume = {9}, number = {3}, pages = {196-197}, pmid = {38020953}, issn = {2455-4626}, } @article {pmid38020714, year = {2023}, author = {Wu, J and Yang, H and Yu, D and Yang, X}, title = {Blood-derived product therapies for SARS-CoV-2 infection and long COVID.}, journal = {MedComm}, volume = {4}, number = {6}, pages = {e426}, pmid = {38020714}, issn = {2688-2663}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of large-scale transmission and has caused the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 may experience persistent long-term health issues, known as long COVID. Both acute SARS-CoV-2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood-derived products are important strategies to combat the serious damage caused by COVID-19. Since the emergence of COVID-19, various blood-derived products that target or do not target SARS-CoV-2 have been investigated for therapeutic applications. SARS-CoV-2-targeting blood-derived products, including COVID-19 convalescent plasma, COVID-19 hyperimmune globulin, and recombinant anti-SARS-CoV-2 neutralizing immunoglobulin G, are virus-targeting and can provide immediate control of viral infection in the short term. Non-SARS-CoV-2-targeting blood-derived products, including intravenous immunoglobulin and human serum albumin exhibit anti-inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS-CoV-2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood-derived product therapies for COVID-19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.}, } @article {pmid38020172, year = {2023}, author = {Karampitsakos, T and Spagnolo, P and Tzouvelekis, A}, title = {Editorial: Immune-mediated lung injury.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1292074}, pmid = {38020172}, issn = {2296-858X}, } @article {pmid38020101, year = {2023}, author = {Stengel, S and Gölz, L and Kolb, J and Tarbet, K and Völler, S and Koetsenruijter, J and Szecsenyi, J and Merle, U}, title = {First insights into multidisciplinary and multispecialty long COVID networks-a SWOT analysis from the perspective of ambulatory health care professionals.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1251915}, pmid = {38020101}, issn = {2296-858X}, abstract = {INTRODUCTION: Multidisciplinary and multispecialty approaches with central integration of primary care, individualized long-term rehabilitative care, and multidisciplinary care pathways are recommended by international consortia to face the challenges of care of long COVID. Two regional long COVID networks-Rhein-Neckar (RN) and Ludwigsburg (LU) have emerged as ad hoc examples of best practice in Southern Germany. The aim of the community case study is to provide first insights into the experiences of the networks.

METHODS: The exploratory observational study was conducted between April and June 2023, focusing on an observation period of just under 24 months and using a document analysis supported by MAXQDA and SWOT analysis with ambulatory health care professionals in two online group discussions.

RESULTS: The document analysis revealed that both networks have defined network participants who have agreed on common goals and patient pathways and have established ways of communicating, organizing, and collaborating. Both networks agreed on a primary care-based, multidisciplinary and multispecialty approach. The main differences in realization emerged in LU as a focus on the ambulatory setting and very concrete application to individual patients, while RN showed a focus on an intersectoral character with participation of the specialized university hospital sector, knowledge transfer and a supra-regional approach with the involvement of the meso and macro level. The SWOT analysis (n = 14 participants, n = 6 male, 7 physicians (4 disciplines), 7 therapists (5 professions)) showed strengths such as resulting collaboration, contribution to knowledge transfer, and improvement of care for individual patients. As barriers, e.g., lack of reimbursement, high efforts of care, and persistent motivation gaps became apparent. Potentials mentioned were, e.g., transferability to other diseases such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, promotion of addressing a "difficult topic" and promotion of intersectoral care concepts; risks mentioned were, e.g., limited network resources and negative effects on the development of other structures.

CONCLUSION: Resulting implications for practice and research address a call to policy makers and funders to support further research to find out what generalizable results regarding usefulness, effectiveness, and efficiency including transferability to other post-infectious diseases can be derived.}, } @article {pmid38020100, year = {2023}, author = {Huang, D and Yu, Y and Lu, J and Tan, F and Shi, Y}, title = {Biologics targeting IL-17 and IL-23 maintain stability in patients with psoriasis during COVID-19 infection: a case-control study.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1280965}, pmid = {38020100}, issn = {2296-858X}, abstract = {BACKGROUND: Psoriasis is a chronic and refractory skin disease. The emergence of biologics provides more options for the treatment of psoriasis, but the COVID-19 pandemic poses challenges for the management of psoriasis.

OBJECTIVES: The purpose of this study was to investigate the effect of different biologics on the stabilization of psoriasis during COVID-19 infection in China.

METHODS: This is a single-center, observational, retrospective, case-control study. Using our database, we conducted a remote dermatologic study by means of questionnaire follow-up or telephone follow-up to collect general information of patients, information related to COVID-19 infection and conditions of psoriasis for comparison and further analysis between groups.

RESULTS: Our study ultimately included 274 patients for analysis. We found that the patients in this collection had mild symptoms of COVID-19 infection, and only 13 of them needed to go to the hospital for medical treatment. Further studies found that in biologics, relative to tumor necrosis factor-α inhibitors (TNF-αi), interleukin-17 inhibitors (IL-17i) and interleukin-23 inhibitors (IL-23i) are both protective factors in flare-up of psoriasis [IL-17i: OR (95% CI) = 0.412 (0.189-0.901); IL-23i: OR (95% CI) = 0.291 (0.097-0.876)]. In addition, we also found that the proportion of people with increased psoriasis developing long COVID-19 increased, and we speculated that increased psoriasis may be a potential risk factor for long COVID-19.

CONCLUSION: Our study showed that the use of IL-17i and IL-23i was a protective factor for psoriasis compared with TNF-αi, and could keep the psoriasis stable.}, } @article {pmid38019841, year = {2023}, author = {Hoshijima, H and Mihara, T and Seki, H and Hyuga, S and Kuratani, N and Shiga, T}, title = {Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0250909}, pmid = {38019841}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Incidence ; Anosmia ; SARS-CoV-2 ; Headache/epidemiology/etiology ; Dyspnea/epidemiology ; }, abstract = {BACKGROUND: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as "long COVID" or "post-acute sequelae of SARS-CoV-2 infection" (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

METHODS: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

RESULTS: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

CONCLUSIONS: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.}, } @article {pmid38019493, year = {2023}, author = {Eastman, Q}, title = {Study Shows Businesses Selling Unapproved Stem Cell Treatments Have Turned to Long COVID.}, journal = {JAMA}, volume = {330}, number = {24}, pages = {2326-2327}, doi = {10.1001/jama.2023.23897}, pmid = {38019493}, issn = {1538-3598}, mesh = {Humans ; Commerce ; COVID-19/economics/therapy ; Marketing ; *Post-Acute COVID-19 Syndrome/economics/therapy ; Stem Cells ; *Stem Cell Transplantation/economics ; *Drug Approval ; }, } @article {pmid38018136, year = {2023}, author = {Boccatonda, A and Campello, E and Simion, C and Simioni, P}, title = {Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection.}, journal = {Expert review of hematology}, volume = {16}, number = {12}, pages = {1035-1048}, doi = {10.1080/17474086.2023.2288154}, pmid = {38018136}, issn = {1747-4094}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Endothelial Cells/metabolism ; Inflammation ; *Thrombosis/etiology/metabolism ; *Thrombophilia/etiology ; }, abstract = {INTRODUCTION: both symptomatic and asymptomatic SARS-CoV-2 infections - coined Coronavirus disease 2019 (COVID-19) - have been linked to a higher risk of cardiovascular events after recovery.

AREAS COVERED: our review aims to summarize the latest evidence on the increased thrombotic and cardiovascular risk in recovered COVID-19 patients and to examine the pathophysiological mechanisms underlying the interplay among endothelial dysfunction, inflammatory response and coagulation in long-COVID. We performed a systematic search of studies on hypercoagulability, endothelial dysfunction and inflammation after SARS-CoV-2 infection.

EXPERT OPINION: endothelial dysfunction is a major pathophysiological mechanism responsible for most clinical manifestations in COVID-19. The pathological activation of endothelial cells by a virus infection results in a pro-adhesive and chemokine-secreting phenotype, which in turn promotes the recruitment of circulating leukocytes. Cardiovascular events after COVID-19 appear to be related to persistent immune dysregulation. Patients with long-lasting symptoms display higher amounts of proinflammatory molecules such as tumor necrosis factor-α, interferon γ and interleukins 2 and 6. Immune dysregulation can trigger the activation of the coagulation pathway. The formation of extensive microclots in vivo, both during acute COVID-19 and in long-COVID-19, appears to be a relevant mechanism responsible for persistent symptoms and cardiovascular events.}, } @article {pmid38017502, year = {2023}, author = {Bejaoui, Y and Humaira Amanullah, F and Saad, M and Taleb, S and Bradic, M and Megarbane, A and Ait Hssain, A and Abi Khalil, C and El Hajj, N}, title = {Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.}, journal = {Clinical epigenetics}, volume = {15}, number = {1}, pages = {186}, pmid = {38017502}, issn = {1868-7083}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/genetics ; Post-Acute COVID-19 Syndrome ; DNA Methylation ; SARS-CoV-2 ; Hospitalization ; *Respiratory Distress Syndrome/genetics ; Acceleration ; Epigenesis, Genetic ; }, abstract = {BACKGROUND: Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated.

RESULTS: In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died.

CONCLUSIONS: EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.}, } @article {pmid38017426, year = {2023}, author = {Guo, B and Zhao, C and He, MZ and Senter, C and Zhou, Z and Peng, J and Li, S and Fitzpatrick, AL and Lindström, S and Stebbins, RC and Noppert, GA and Li, C}, title = {Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {468}, pmid = {38017426}, issn = {1741-7015}, support = {R00 AG062749/AG/NIA NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; R00AG062749/GF/NIH HHS/United States ; R01AG075719/GF/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Arrhythmias, Cardiac/epidemiology/etiology ; Chest Pain ; }, abstract = {INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics.

METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis.

RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications.

CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.}, } @article {pmid38016742, year = {2023}, author = {}, title = {Do allergic conditions increase the risk of developing Long-COVID after SARS-CoV-2 infection?.}, journal = {Saudi medical journal}, volume = {44}, number = {12}, pages = {1312}, pmid = {38016742}, issn = {1658-3175}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Hypersensitivity ; }, } @article {pmid38016374, year = {2024}, author = {Wang, P and Zhang, S and Qi, C and Wang, C and Zhu, Z and Shi, L and Cheng, L and Zhang, X}, title = {Blood microbial analyses reveal long-term effects of SARS-CoV-2 infection on patients who recovered from COVID-19.}, journal = {Computers in biology and medicine}, volume = {168}, number = {}, pages = {107721}, doi = {10.1016/j.compbiomed.2023.107721}, pmid = {38016374}, issn = {1879-0534}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Disease Progression ; Macrophages ; RNA-Seq ; }, abstract = {OBJECTIVE: Few symptoms persist for a long time after patients recover from COVID-19, called "long COVID". We explored the potential microbial risk factors for COVID-19 for a deeper understanding and assistance in the follow-up treatment of these sequelae.

METHODS: Microbiome re-annotation was performed using whole blood RNA-Seq data collected from recovered COVID-19 patients and healthy controls at multiple time points. Subsequently, a series of downstream analyses were conducted to reveal the microbial characteristics of patients who recovered from SARS-CoV-2 infection.

RESULTS: The blood microbiome at 12 weeks post-infection was most evidently disturbed, including an increasing ratio of Bacillota/Bacteroidota and a higher microbial alpha diversity. In addition, a group of pathogenic microbes at 12 weeks post-infection were identified, including Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were positively associated with host genes involved in immune regulatory and olfactory transduction pathways. Several microbes, such as Streptococcus pneumoniae were associated with infiltrating immune cells, such as M2 macrophages.

CONCLUSION: This study provides insights into the relationship between the blood microbiome and COVID-19 sequelae. Several pathogenic microbes were enriched in recovered COVID-19 patients and thus affected host genes participating in the immune and olfactory transduction pathways, which play critical roles in COVID-19 sequelae.}, } @article {pmid38015788, year = {2023}, author = {Chen, K and Rogers, ML and Clark, MA and Zandstra, T and Lovgren, L and Beaudoin, FL and Chambers, LC}, title = {Pandemic Preparedness and the Workforce: Employer Experiences with Long COVID.}, journal = {Rhode Island medical journal (2013)}, volume = {106}, number = {11}, pages = {54-61}, pmid = {38015788}, issn = {2327-2228}, support = {R25 MH083620/MH/NIMH NIH HHS/United States ; T32 DA013911/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; Cross-Sectional Studies ; SARS-CoV-2 ; *COVID-19 ; Workforce ; }, abstract = {BACKGROUND: Although viral infections, including SARS-CoV-2, can cause persistent symptoms and functional limitations, the impact of post-viral syndromes on workplaces is uncertain.

METHODS: We conducted a cross-sectional study of workplaces in Rhode Island in the D&B Hoovers database (September-October 2022). Eligible workplaces had ≥1 contact with a valid email address and ≥2 paid employees. Participants completed a survey on the impact of Long COVID (post-viral syndrome of SARS-CoV-2) on their workplace.

RESULTS: Of 6,149 eligible workplaces, 484 (8%) participated. Awareness of Long COVID among workplace leaders was limited. Overall, 28% of workplaces had any employees report having Long COVID. Of those, 14% had ≥1 employee discontinue employment, 45% had ≥1 employee reduce their workload, and 22% had ≥1 employee request an accommodation due to having Long COVID; 80% of employers reported improvement in employee productivity with accommodations.

CONCLUSION: Pandemic preparations for the long-term impacts of post-viral syndromes should consider workplace settings.}, } @article {pmid38014645, year = {2024}, author = {Volk, P and Rahmani Manesh, M and Warren, ME and Besko, K and Gonçalves de Andrade, E and Wicki-Stordeur, LE and Swayne, LA}, title = {Long-term neurological dysfunction associated with COVID-19: Lessons from influenza and inflammatory diseases?.}, journal = {Journal of neurochemistry}, volume = {168}, number = {10}, pages = {3500-3511}, doi = {10.1111/jnc.16016}, pmid = {38014645}, issn = {1471-4159}, support = {GA4-177766/CAPMC/CIHR/Canada ; PJT 185887/CAPMC/CIHR/Canada ; GA4-177766/CAPMC/CIHR/Canada ; PJT 185887/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *COVID-19/complications ; *Influenza, Human/complications/epidemiology ; Nervous System Diseases/etiology ; SARS-CoV-2/pathogenicity ; Cognitive Dysfunction/etiology ; Inflammation ; Fatigue/etiology ; }, abstract = {As the COVID-19 pandemic persists, SARS-CoV-2 infection is increasingly associated with long-term neurological side effects including cognitive impairment, fatigue, depression, and anxiety, colloquially known as "long-COVID." While the full extent of long-COVID neuropathology across years or even decades is not yet known, we can perhaps take direction from long-standing research into other respiratory diseases, such as influenza, that can present with similar long-term neurological consequences. In this review, we highlight commonalities in the neurological impacts of influenza and COVID-19. We first focus on the common potential mechanisms underlying neurological sequelae of long-COVID and influenza, namely (1) viral neurotropism and (2) dysregulated peripheral inflammation. The latter, namely heightened peripheral inflammation leading to central nervous system dysfunction, is emerging as a shared mechanism in various peripheral inflammatory or inflammation-associated diseases and conditions. We then discuss historical and modern examples of influenza- and COVID-19-associated cognitive impairment, depression, anxiety, and fatigue, revealing key similarities in their neurological sequelae. Although we are learning that the effects of influenza and COVID differ somewhat in terms of their influence on the brain, as the impacts of long-COVID grow, such comparisons will likely prove valuable in guiding ongoing research into long-COVID, and perhaps foreshadow what could be in store for individuals with COVID-19 and their brain health.}, } @article {pmid38013408, year = {2024}, author = {Cimolai, N}, title = {COVID-19 among infants: key clinical features and remaining controversies.}, journal = {Clinical and experimental pediatrics}, volume = {67}, number = {1}, pages = {1-16}, pmid = {38013408}, issn = {2713-4148}, abstract = {Infants aged <1 year represent a seemingly more susceptible pediatric subset for infections. Despite this, coronavirus disease 2019 (COVID-19) infection has not been proven as more serious in this age group (outside the very early neonatal period) than in others. Indeed, a considerable number of asymptomatic infections have been recorded, and the symptoms and morbidity associated with COVID- 19 differ minimally from those of other respiratory viral infections. Whether due to an abundance of caution or truly reduced susceptibility, infections in infants have not raised the same profile as those in other age groups. In addition to direct severe acute respiratory syndrome coronavirus 2 diagnostic tests, laboratory markers that differentiate COVID-19 from other viral infections lack specificity in infants. Gastrointestinal presentations are common, and the neurological complications of infection mirror those of other respiratory viral infections. There have been relatively few reports of infant deaths. Under appropriate precautions, breastfeeding in the context of maternal infections has been associated with tangible but infrequent complications. Vaccination during pregnancy provides protection against infection in infants, at least in the early months of life. Multi-inflammatory syndrome in children and multi-inflammatory syndrome in neonates are commonly cited as variants of COVID-19; however, their clinical definitions remain controversial. Similarly, reliable definitions of long COVID in the infant group are controversial. This narrative review examines the key clinical and laboratory features of COVID-19 in infants and identifies several areas of science awaiting further clarification.}, } @article {pmid38013390, year = {2024}, author = {Modji, KKS and McCoy, KE and Creswell, PD and Morris, CR and Tomasallo, CD}, title = {Long COVID Among Wisconsin Workers in the Workers' Compensation System: Associations With Sociodemographics, Vaccination, and Predominant Variant Period From March 1, 2020 to July 31, 2022.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {2}, pages = {e34-e41}, doi = {10.1097/JOM.0000000000003018}, pmid = {38013390}, issn = {1536-5948}, support = {U60 OH010898/OH/NIOSH CDC HHS/United States ; }, mesh = {Humans ; Adult ; *Workers' Compensation ; Post-Acute COVID-19 Syndrome ; Wisconsin/epidemiology ; Retrospective Studies ; COVID-19 Vaccines ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Vaccination ; }, abstract = {OBJECTIVE: This analysis aimed to determine the likelihood of developing long COVID among Wisconsin workers while adjusting for sociodemographics, COVID-19 vaccination, industry, and occupation.

METHODS: This retrospective analysis determined the odds ratios of developing long COVID among Wisconsin workers who were compensated for COVID-19 lost time during March 1, 2020 to July 31, 2022.

RESULTS: A total of 234 workers (11.7%) were determined to have long COVID. Factors associated with long COVID were age ≥40 years, non-White race, infection occurrence during the initial and Omicron variant dominant periods, and the absence of COVID-19 vaccination. Workers in manufacturing and public administration were more likely to develop long COVID compared with those in health care and social assistance.

CONCLUSIONS: Long COVID disproportionately affects some worker groups. This calls for more worker protection and preventative care to mitigate its impact.}, } @article {pmid38008902, year = {2024}, author = {Tan, S and Pryor, AJG and Melville, GW and Fischer, O and Hewitt, L and Davis, KJ}, title = {The lingering symptoms of post-COVID-19 condition (long-COVID): a prospective cohort study.}, journal = {Internal medicine journal}, volume = {54}, number = {2}, pages = {224-233}, doi = {10.1111/imj.16251}, pmid = {38008902}, issn = {1445-5994}, mesh = {Female ; Humans ; Chronic Disease ; *Chronic Pain ; *COVID-19/epidemiology ; COVID-19 Testing ; Fatigue/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Male ; }, abstract = {BACKGROUND: Longer-term symptoms (long COVID) may be present in seemingly recovered patients for several months and can be debilitating.

AIM: To investigate the prevalence and type of symptoms in those with a prior COVID-19 diagnosis.

METHODS: This prospective, longitudinal observational study commenced in July 2020 investigating the longer-term health impacts of COVID-19. Participants were recruited via public health units and media publicity. Surveys were completed upon enrolment, and at 1, 3, 6 and 12 months. Outcome measures included incidence of activity limitations and symptoms against health and vaccination status, age and gender.

RESULTS: Overall, 339 participants were recruited. At 3 months after COVID-19, 66.8% reported symptoms, and 44.8% were still experiencing symptoms at 12 months. Fatigue was most common at every point (between 53.1% and 33.1%). Pain symptoms increased in relative prevalence over time, whereas respiratory/pulmonary-type symptoms decreased substantially after 3 months. Females and younger people were more likely to experience symptoms in the early stages of long COVID (P < 0.01) and those with more comorbidities in the latter stages (P < 0.001). Vaccination showed a statistically significant protective effect against symptoms (P < 0.01-0.001).

CONCLUSION: Long-term COVID-19 symptoms exist among recovered patients up to 12 months after contracting the virus. Fatigue is a primary contributor, while chronic pain became more problematic after 6 months. Vaccination was a factor in preventing long-term symptoms and aiding faster recovery from symptoms. Further work exploring additional contributors to symptom prevalence would assist in developing appropriate follow-up care.}, } @article {pmid38007044, year = {2024}, author = {Ponirakis, G and Odriozola, A and Ortega, L and Martinez, L and Odriozola, S and Torrens, A and Coroleu, D and Martínez, S and Sanz, X and Ponce, M and Meije, Y and Clemente, M and Duarte, A and Odriozola, MB and Malik, RA}, title = {Quantitative sensory testing defines the trajectory of sensory neuropathy after severe COVID-19.}, journal = {Diabetes research and clinical practice}, volume = {207}, number = {}, pages = {111029}, doi = {10.1016/j.diabres.2023.111029}, pmid = {38007044}, issn = {1872-8227}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Sensory Thresholds ; *Neuralgia/diagnosis/etiology ; *Diabetes Mellitus ; Vibration ; *Diabetic Neuropathies/diagnosis/etiology ; }, abstract = {AIMS: To assess sensory neuropathy development after severe COVID-19.

METHODS: Patients with severe COVID-19 underwent assessment of neuropathic symptoms, tendon reflexes, and quantitative sensory testing to evaluate vibration (VPT), cold (CPT), warm (WPT) and heat perception thresholds (HPT) within 1-3 weeks of admission and after 1-year.

RESULTS: 32 participants with severe COVID-19 aged 68.6 ± 12.4 (18.8 % diabetes) were assessed. At baseline, numbness and neuropathic pain were present in 56.3 % and 43.8 % of participants, respectively. On the feet, VPT, WPT, and HPT were abnormal in 81.3 %, CPT was abnormal in 50.0 % and HPT on the face was abnormal in 12.5 % of patients. At 1-year follow-up, the prevalence of abnormal VPT (81.3 % vs 50.0 %, P < 0.01), WPT (81.3 % vs 43.8 %, P < 0.01), and HPT (81.3 % vs 50.0 %, P < 0.01) decreased, with no change in CPT (P = 0.21) on the feet or HPT on the face (P = 1.0). Only participants without diabetes recovered from an abnormal VPT, CPT, and WPT. Patients with long-COVID (37.5 %) had comparable baseline VPT, WPT and CPT with those without long-COVID (P = 0.07-0.69).

CONCLUSIONS: Severe COVID-19 is associated with abnormal vibration and thermal thresholds which are sustained for up to 1 year in patients with diabetes. Abnormal sensory thresholds have no association with long-COVID development.}, } @article {pmid38006716, year = {2023}, author = {Panzeri, A and DeVita, M and Di Rosa, E and Bottesi, G and Brundisini, V and Guarrera, C and Ravelli, A and Ponza, I and Cattelan, A and Volpe, B and Iannizzi, P and Ghisi, M and Schiavo, R and Mapelli, D}, title = {Trauma Shaping the Psychopathological Correlates of Patients with Long-COVID: A 6-Months Longitudinal Study with Repeated Measures Mixed Models.}, journal = {Psychiatry research}, volume = {330}, number = {}, pages = {115609}, doi = {10.1016/j.psychres.2023.115609}, pmid = {38006716}, issn = {1872-7123}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Research Design ; Longitudinal Studies ; Anxiety Disorders ; *Stress Disorders, Post-Traumatic ; }, abstract = {This research aimed at investigating how the experience of trauma can influence the psychological correlates of long-COVID over time in a clinical sample of patients hospitalized because of COVID-19. Through a longitudinal research design, 70 post-acute patients with COVID-19 were followed-up after hospital discharge in 3-time points up to 6 months and completed the Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) and the Symptoms Checklist-90-Revised (SCL-90 R). Repeated measures mixed models with random intercept were used to evaluate the effect of trauma (yes/no) over time (T1, T2, T3) on the SCL-90-R scales. Results showed that patients with trauma display significantly worse psychological outcomes in all the SCL-90-R dimensions [all padj < .05 for the principal effects of trauma(y)], especially in symptoms of depression [time 2 vs time 1*trauma(y): b = -3.86, 95%CI (-7.18, -0.53), padj = .035; time 3 vs time 1*trauma(y): b = -4.77, 95%CI (-8.10, -1.45), padj = .011], anxiety [time 3 vs time 1*trauma(y): b = -4.54, 95%CI (-7.72, -1.37), padj = .011], and obsessive-compulsive difficulties [time 3 vs time 1*trauma(y): b = -4.03, 95%CI (-7.20, -0.86), padj = .027]. These findings shed light on the long-term psychological consequences of COVID-19 among hospitalized patients and highlight the key role of trauma, suggesting its assessment to tailor psychological interventions.}, } @article {pmid38004261, year = {2023}, author = {Mohan, A and Iyer, VA and Kumar, D and Batra, L and Dahiya, P}, title = {Navigating the Post-COVID-19 Immunological Era: Understanding Long COVID-19 and Immune Response.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, pmid = {38004261}, issn = {2075-1729}, abstract = {The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. COVID-19 significantly impacted the immune system, and understanding the immunological consequences of COVID-19 is essential for developing effective treatment strategies. The purpose of this review is to comprehensively explore and provide insights into the immunological aspects of long COVID-19, a phenomenon where individuals continue to experience a range of symptoms and complications, even after the acute phase of COVID-19 infection has subsided. The immune system responds to the initial infection by producing various immune cells and molecules, including antibodies, T cells, and cytokines. However, in some patients, this immune response becomes dysregulated, leading to chronic inflammation and persistent symptoms. Long COVID-19 encompasses diverse persistent symptoms affecting multiple organ systems, including the respiratory, cardiovascular, neurological, and gastrointestinal systems. In the post-COVID-19 immunological era, long COVID-19 and its impact on immune response have become a significant concern. Post-COVID-19 immune pathology, including autoimmunity and immune-mediated disorders, has also been reported in some patients. This review provides an overview of the current understanding of long COVID-19, its relationship to immunological responses, and the impact of post-COVID-19 immune pathology on patient outcomes. Additionally, the review addresses the current and potential treatments for long COVID-19, including immunomodulatory therapies, rehabilitation programs, and mental health support, all of which aim to improve the quality of life for individuals with long COVID-19. Understanding the complex interplay between the immune system and long COVID-19 is crucial for developing targeted therapeutic strategies and providing optimal care in the post-COVID-19 era.}, } @article {pmid38003950, year = {2023}, author = {Obeidat, FS and Alghwiri, AA and Whitney, SL}, title = {Predictors of Dizziness and Hearing Disorders in People with Long COVID.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {11}, pages = {}, pmid = {38003950}, issn = {1648-9144}, support = {2021-2022/36//University of Jordan/ ; }, mesh = {Female ; Humans ; Male ; *COVID-19/complications ; *Deafness ; Dizziness/etiology/diagnosis ; Fatigue/etiology ; Hearing Disorders ; *Hearing Loss/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Adolescent ; Young Adult ; Adult ; }, abstract = {Background and Objectives: Individuals report persistent symptoms after becoming infected by SARS-CoV-2 (COVID-19) that last for >4 weeks (long-COVID syndrome). Dizziness and hearing loss have been reported among long-COVID symptoms. However, little is known about the potential predictors of dizziness and hearing loss in individuals with long COVID. This study aimed to explore the presence and correlates of dizziness and hearing loss in a sample of people with long-COVID syndrome. Materials and Methods: Individuals aged 18 years and older who were infected with COVID-19 at least 8 weeks prior to the start of the study were included if they were not diagnosed with dizziness or hearing loss before getting COVID-19. Demographics and COVID-19-related information were collected. Participants completed the Dizziness Handicap Inventory (DHI), Activities-Specific Balance Confidence (ABC) scale, Falls Efficacy Scale International (FES-I), Modified Fatigue Impact Scale (MFIS), and Medical Outcomes Study Short Form 12 (SF-12). Finally, hearing was assessed using pure-tone audiometry (PTA) in a subsample. Results: Two hundred and nine individuals (66% female) with a mean (SD) age of 27 (9) participated in the study. Perceived dizziness and hearing loss were reported in 26 and 15.3% of the sample, respectively. Logistic regression was conducted to identify potential predictors of dizziness and hearing loss separately. After controlling for age and severity of dizziness, female sex and high fatigue severity were associated with an increased likelihood of reporting dizziness (R[2] = 31%). The severity of dizziness and neurological symptoms during the acute stage of COVID-19 were associated with an increased likelihood of reporting hearing loss (R[2] = 10.4%) after controlling for age. Conclusions: Dizziness and hearing loss present in long COVID and can be disabling. Females with high levels of fatigue should be questioned about persistent dizziness. Hearing loss should be considered in individuals with neurological symptoms and severe dizziness as a consequence of long COVID.}, } @article {pmid38003921, year = {2023}, author = {Tabacof, L and Wood, J and Breyman, E and Tosto-Mancuso, J and Kelly, A and Wilkey, K and Zhang, C and Putrino, D and Kontorovich, A}, title = {Dysautonomia, but Not Cardiac Dysfunction, Is Common in a Cohort of Individuals with Long COVID.}, journal = {Journal of personalized medicine}, volume = {13}, number = {11}, pages = {}, pmid = {38003921}, issn = {2075-4426}, abstract = {Despite the prevalence of dysautonomia in people with Long COVID, it is currently unknown whether Long COVID dysautonomia is routinely accompanied by structural or functional cardiac alterations. In this retrospective observational study, the presence of echocardiographic abnormalities was assessed. Left ventricular (LV) chamber sizes were correlated to diagnostic categories and symptoms via standardized patient-reported outcome (PRO) questionnaires. A total of 203 individuals with Long COVID without pre-existing cardiac disease and with available echocardiograms were included (mean age, 45 years; 67% female). Overall, symptoms and PRO scores for fatigue, breathlessness, quality of life, disability, anxiety and depression were not different between those classified with post-COVID dysautonomia (PCD, 22%) and those unclassified (78%). An LV internal diameter at an end-diastole z score < -2 was observed in 33 (16.5%) individuals, and stroke volume (SV) was lower in the PCD vs. unclassified subgroup (51.6 vs. 59.2 mL, 95% C.I. 47.1-56.1 vs. 56.2-62.3). LV end-diastolic volume (mean diff. (95% CI) -13 [-1--26] mL, p = 0.04) and SV (-10 [-1--20] mL, p = 0.03) were smaller in those individuals reporting a reduction in physical activity post-COVID-19 infection, and smaller LVMI was weakly correlated with worse fatigue (r = 0.23, p = 0.02). The majority of individuals with Long COVID report shared symptoms and did not demonstrate cardiac dysfunction on echocardiography.}, } @article {pmid38002841, year = {2023}, author = {Newlands, F and Goddings, AL and Juste, M and Boyd, H and Nugawela, MD and Pinto Pereira, SM and Whelan, E and Whittaker, E and Stephenson, T and Heyman, I and Chalder, T and Dalrymple, E and CLoCk Consortium, and Segal, T and Shafran, R}, title = {Children and Young People with Long COVID-Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {38002841}, issn = {2227-9067}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described.

PURPOSE: (1) to describe the characteristics of children aged 11-17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom's largest research study of Long COVID in children (CLoCk).

DESIGN: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk.

RESULTS: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk.

CONCLUSIONS: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group.}, } @article {pmid38002386, year = {2023}, author = {Huang, SM and Hsieh, CY and Ting, JU and De Castro-Cruz, KA and Wang, CC and Lee, CJ and Tsai, PW}, title = {Anti-COVID-19, Anti-Inflammatory, and Anti-Osteoarthritis Activities of Sesamin from Sesamum indicum L.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {38002386}, issn = {2306-5354}, support = {No. 10821//Taiwan's Ministry of Health and Welfare/ ; }, abstract = {During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25-50 μM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25-50 μM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development.}, } @article {pmid38002002, year = {2023}, author = {Hu, Y and Liu, Y and Zheng, H and Liu, L}, title = {Risk Factors for Long COVID in Older Adults.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38002002}, issn = {2227-9059}, support = {32070923//National Natural Science Foundation of China/ ; 2022SCP010//The High-level Talent Promotion and Training Project of Kunming/ ; 2021-I2M-1-043//CAMS Innovation Fund for Medical Sciences/ ; }, abstract = {As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID. Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as "immunosenescence". This further exacerbates "inflammaging" and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated. This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.}, } @article {pmid38001354, year = {2024}, author = {Bergamaschi, G and Barteselli, C and Calabretta, F and Lenti, MV and Merli, S and Rossi, CM and Di Sabatino, A}, title = {Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection.}, journal = {Internal and emergency medicine}, volume = {19}, number = {1}, pages = {125-133}, pmid = {38001354}, issn = {1970-9366}, mesh = {Humans ; Female ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Internal Medicine ; Disease Progression ; Immunoglobulin M ; }, abstract = {Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period. We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12 months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001. Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.}, } @article {pmid38000377, year = {2024}, author = {Routen, A and Khunti, K}, title = {Long-term outcomes in hospitalised COVID-19 survivors and future research priorities.}, journal = {The Lancet. Respiratory medicine}, volume = {12}, number = {1}, pages = {7-8}, doi = {10.1016/S2213-2600(23)00410-1}, pmid = {38000377}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 ; Survivors ; Research ; }, } @article {pmid38000376, year = {2024}, author = {Zhang, H and Huang, C and Gu, X and Wang, Y and Li, X and Liu, M and Wang, Q and Xu, J and Wang, Y and Dai, H and Zhang, D and Cao, B}, title = {3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study.}, journal = {The Lancet. Respiratory medicine}, volume = {12}, number = {1}, pages = {55-66}, doi = {10.1016/S2213-2600(23)00387-9}, pmid = {38000376}, issn = {2213-2619}, mesh = {Humans ; Longitudinal Studies ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Patient Discharge ; Reinfection ; Cohort Studies ; China/epidemiology ; }, abstract = {BACKGROUND: There is a paucity of data on the natural trajectory of outcomes in survivors of COVID-19 beyond 2 years after symptom onset, and no evidence exists on the effect of re-infection in people with long COVID symptoms. We aimed to investigate the 3-year health outcomes of COVID-19 survivors and the effect of omicron re-infection.

METHODS: In this single-centre, longitudinal cohort study, we recruited participants with confirmed COVID-19 who were discharged from the Jin Yin-tan hospital in Wuhan, China, between Jan 7 and May 29, 2020. Participants completed three follow-up visits at 6 months (June 16 to Sept 13, 2020), 1 year (Dec 16, 2020, to Feb 7, 2021), and 2 years (Nov 16, 2021, to Jan 10, 2022) since symptom onset (reported previously). At 1-year follow-up, community controls without a history of SARS-CoV-2 infection were recruited from two communities in Wuhan and at 2 years were matched (1:1) with survivors of COVID-19 who underwent pulmonary function tests. We did a 3-year follow-up from Feb 23, 2023, to April 20, 2023, after the omicron (B.1.1.529) wave in winter, 2022. All eligible survivors of COVID-19 and community controls matched at 2-year follow-up were invited to the outpatient clinic at the hospital to complete several face-to-face questionnaires, a 6-min walking test (6MWT), and laboratory tests. A subgroup of survivors of COVID-19 identified by stratified sampling on the basis of disease severity scale score during hospitalisation and community controls underwent pulmonary function tests. Survivors of COVID-19 who received high-resolution CT and showed abnormal lung images at 2-year follow-up were invited for another assessment. We identified participants with and without long COVID at 2 years. The primary outcomes were sequelae symptoms, omicron infection, lung function, and chest imaging at the 3-year follow-up.

FINDINGS: Of 1359 COVID-19 survivors who completed 2-year and 3-year follow-up, 728 (54%) had at least one sequelae symptom at 3 years after symptom onset and before omicron infection, mainly mild to moderate severity. During the omicron wave, participants with long COVID at 2 years had a significantly higher proportion of re-infection (573 [76%] of 753 vs 409 [67%] of 606 without long COVID; p=0·0004), pneumonia (27 [5%] of 568 vs seven [2%] of 403; p=0·012). 3 months after omicron infection, 126 (62%) of 204 survivors with long COVID at 2 years had newly occurring or worse symptoms, which was significantly higher than the proportion in the non-long COVID group (85 [41%] of 205; p<0·0001) and community controls (81 [40%] of 205; p<0·0001), and not significantly different between COVID-19 survivors without long COVID and matched community controls (85 [41%] of 205 vs 81 [39%] of 206; p=0·66). Re-infection was a risk factor for dyspnoea (odds ratio 1·36 [95% CI 1·04 to 1·77]; p=0·023), anxiety or depression (OR 1·65 [1·24 to 2·20]; p=0·0007), EuroQol visual analogue scale score (β -4·51 [-6·08 to -2·95]; p<0·0001), but not for reduced daily activity (0·72 [0·38 to 1·37]; p=0·32) at 3 years. Lung function of survivors at 3 years was similar to that of matched community controls. We found irregular line, traction bronchiectasis, subpleural lines and ground glass opacity at 3 years, but the volume ratio of lung lesion to total lung was only 0·2-0·3%.

INTERPRETATION: Most long COVID symptoms at 3 years were mild to moderate, with lung function recovering to levels of matched controls. Survivors with long COVID had a higher proportion of participants with re-infection and newly occurring or worse symptoms 3 months after omicron infection than those without long COVID. Re-infection had increased symptom occurrence but not increased reduced daily activity. Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research.

FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China.}, } @article {pmid37999770, year = {2024}, author = {Boesl, F and Goereci, Y and Gerhard, A and Bremer, B and Raeder, V and Schweitzer, F and Hoppmann, U and Behrens, J and Bellmann-Strobl, J and Paul, F and Wildemann, B and Jarius, S and Prüss, H and Audebert, HJ and Warnke, C and Franke, C}, title = {Cerebrospinal fluid findings in patients with neurological manifestations in post-COVID-19 syndrome.}, journal = {Journal of neurology}, volume = {271}, number = {1}, pages = {59-70}, pmid = {37999770}, issn = {1432-1459}, support = {FR 4479/1-1//Deutsche Forschungsgemeinschaft/ ; PR 1274/8-1//Deutsche Forschungsgemeinschaft/ ; WA 4101/2-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19/complications ; Blood-Brain Barrier ; Autoantibodies ; Cerebrospinal Fluid ; }, abstract = {BACKGROUND: Information on cerebrospinal fluid (CSF) findings in patients with neurological manifestations in post-COVID-19 syndrome is scarce.

METHODS: Retrospective evaluation of 84 CSF samples in patients fulfilling post-COVID-19 criteria in two neurological post-COVID-19 outpatient clinics.

RESULTS: In 68% of samples, all CSF parameters were normal. The most frequent pathological CSF finding was elevation of total protein (median total protein 33.3 mg/dl [total range 18.5-116.2]) in 20 of 83 (24%) samples. The second most prevalent pathological finding was a blood-CSF barrier dysfunction as measured by elevation of QAlb (median QAlb 4.65 [2.4-13.2]) in 11/84 (13%). Pleocytosis was found in only 5/84 (6%) samples and was mild in all of them. CSF-restricted oligoclonal bands were found in 5/83 (6%) samples. Anti-neuronal autoantibodies in CSF were negative in most cases, whilst 12/68 (18%) samples were positive for anti-myelin autoantibodies in serum. PCR for herpesviridae (HSV-1/-2, VZV, EBV, CMV, HHV6) showed, if at all, only weakly positive results in CSF or EDTA whole blood/plasma.

CONCLUSIONS: The majority of samples did not show any pathologies. The most frequent findings were elevation of total protein and blood-CSF barrier dysfunction with no signs of intrathecal inflammation. CSF analysis still keeps its value for exclusion of differential diagnoses.}, } @article {pmid37998290, year = {2023}, author = {Hikmet, RG and Wejse, C and Agergaard, J}, title = {Effect of Vitamin D in Long COVID Patients.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {22}, pages = {}, pmid = {37998290}, issn = {1660-4601}, support = {NNF21OC0066984//Novo Nordisk Foundation/ ; }, mesh = {Humans ; Female ; Male ; Adult ; Vitamin D ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Vitamins ; *Vitamin D Deficiency/epidemiology ; }, abstract = {Vitamin D deficiency has been studied in the context of acute coronavirus disease 2019 (COVID-19), revealing associations with increased severity and mortality. Yet, the influence of vitamin D on long COVID symptoms remains unknown. The purpose of this study is to examine the effect of vitamin D on long COVID symptoms. Over the study period, 50,432 individuals within the catchment area of the outpatient COVID-19 clinic tested positive for SARS-CoV-2 via PCR, with 547 patients subsequently referred to a specialized Post-COVID Clinic, and 447 of them enrolled in the study. Patient-reported symptoms and paraclinical measures including vitamin D were evaluated in 442 patients. The majority of participants were female (72%, n = 320/442). The consumption of alcohol and number of current smokers were low. Low vitamin D was observed in 26% (n = 115/442) of the patients, most commonly in male participants (odds ratio (OR) = 1.77, 95% confidence interval (CI) (1.12, 2.79), p = 0.014). Additionally, low vitamin D was correlated with a younger mean age of 41 years (standard deviation (SD) = 12) as opposed to 48 years (SD = 13) in patients with normal vitamin D levels (OR = 0.96, 95% CI (0.94, 0.97), p < 0.001). While our study population indicated a potentially higher prevalence of vitamin D insufficiency in this population compared to the general population, no significant differences in prevalence of symptom or symptom severity scores were observed between the low and normal vitamin D groups. In patients in a Post-COVID Clinic, we found no association between vitamin D levels and long COVID symptoms.}, } @article {pmid37998081, year = {2023}, author = {Noor, M and McGrath, O and Drira, I and Aslam, T}, title = {Retinal Microvasculature Image Analysis Using Optical Coherence Tomography Angiography in Patients with Post-COVID-19 Syndrome.}, journal = {Journal of imaging}, volume = {9}, number = {11}, pages = {}, pmid = {37998081}, issn = {2313-433X}, abstract = {Several optical coherence tomography angiography (OCT-A) studies have demonstrated retinal microvascular changes in patients post-SARS-CoV-2 infection, reflecting retinal-systemic microvasculature homology. Post-COVID-19 syndrome (PCS) entails persistent symptoms following SARS-CoV-2 infection. In this study, we investigated the retinal microvasculature in PCS patients using OCT-angiography and analysed the macular retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness via spectral domain-OCT (SD-OCT). Conducted at the Manchester Royal Eye Hospital, UK, this cross-sectional study compared 40 PCS participants with 40 healthy controls, who underwent ophthalmic assessments, SD-OCT, and OCT-A imaging. OCT-A images from the superficial capillary plexus (SCP) were analysed using an in-house specialised software, OCT-A vascular image analysis (OCTAVIA), measuring the mean large vessel and capillary intensity, vessel density, ischaemia areas, and foveal avascular zone (FAZ) area and circularity. RNFL and GCL thickness was measured using the OCT machine's software. Retinal evaluations occurred at an average of 15.2 ± 6.9 months post SARS-CoV-2 infection in PCS participants. Our findings revealed no significant differences between the PCS and control groups in the OCT-A parameters or RNFL and GCL thicknesses, indicating that no long-term damage ensued in the vascular bed or retinal layers within our cohort, providing a degree of reassurance for PCS patients.}, } @article {pmid37997145, year = {2023}, author = {Ziauddeen, N and Pantelic, M and O'Hara, ME and Hastie, C and Alwan, NA}, title = {Impact of long COVID-19 on work: a co-produced survey.}, journal = {Lancet (London, England)}, volume = {402 Suppl 1}, number = {}, pages = {S98}, doi = {10.1016/S0140-6736(23)02157-8}, pmid = {37997145}, issn = {1474-547X}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Research Design ; }, abstract = {BACKGROUND: A proportion of people infected with SARS-CoV-2 develop post-COVID-19 condition (also known as long COVID), a predominantly multisystem condition resulting in varying degrees of functional disability limiting day-to-day activities. We aimed to describe the impact of long COVID on work.

METHODS: We co-produced baseline and follow-up online surveys with people with lived experience of long COVID (including three of the co-authors). Respondents were aged 18 years and older with self-reported long COVID following confirmed or suspected COVID-19 infection who were not hospitalised in the first 2 weeks of illness. The baseline survey was administered in November, 2020, using convenience non-probability sampling through social media. Following informed consent, participants completed a follow-up survey at 1 year (November, 2021). Ethics approval was granted by the University of Southampton.

FINDINGS: Of 2210 invited, 1153 (52%) participants responded to the survey (mean age of 47·7 years [SD 10·6], 965 [84%] female, 1096 [95%] White, and 892 [78%] holding a university degree). 54 participants (4·7%) reported recovery at follow-up. Median duration of illness was 19·8 months (IQR 19·3-20·1) at follow-up. An equal proportion reported being unable to work at baseline (20·4%, n=235) and follow-up (20·6%, n=237). However, a higher proportion reported being made redundant or taking early retirement at follow-up (8·9%, n=102) than at baseline (2·2%, n=25). 209 (18·1%) reported losing or resigning or leaving their job due to long COVID at follow-up compared with 170 (14·8%) participants at baseline. 307 (26·6%) participants reported not taking time off-sick due to long COVID at baseline, decreasing to 122 (10·6%) at follow-up. Of the 656 individuals reporting length of time off-sick, 354 (54%) were off-sick for more than 3 months, with 113 (17·2%) off-sick for more than 12 months. Nearly half (47%, n=538) reported a loss in income.

INTERPRETATION: The convenience non-probability sampling limits generalisability. Research is needed in a representative population sample to characterise the effect on working patterns in people with long COVID, particularly in those with less flexible and more physically demanding occupations who may be less able to take time off to recover.

FUNDING: None.}, } @article {pmid37996650, year = {2024}, author = {Mourelatos, P and Vrettou, CS and Diamantopoulos, A and Vassiliou, AG and Jahaj, E and Angelousi, A and Pratikaki, M and Katsaounou, P and Kotanidou, A and Vassiliadi, DA and Dimopoulou, I}, title = {A prospective study on endocrine function in patients with long-COVID symptoms.}, journal = {Hormones (Athens, Greece)}, volume = {23}, number = {1}, pages = {59-67}, pmid = {37996650}, issn = {2520-8721}, mesh = {Adult ; Humans ; Male ; Adrenocorticotropic Hormone ; *COVID-19 ; Dehydroepiandrosterone ; Fatigue ; Hydrocortisone ; *Insulin-Like Growth Factor I ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; RNA, Viral ; SARS-CoV-2 ; Testosterone ; Thyroid Hormones ; Thyrotropin ; Female ; }, abstract = {OBJECTIVE: To investigate hormonal status in patients with long-COVID and explore the interrelationship between hormone levels and long-COVID symptoms.

DESIGN: Prospective observational study.

PARTICIPANTS: Patients who visited our long-COVID outpatients' clinic due to long-COVID symptoms from February 2021 to December 2022.

MEASUREMENTS: Total triiodothyronine, free thyroxine, thyrotropin, thyroglobulin, anti-thyroperoxidase, and antithyroglobulin autoantibodies were measured for thyroid assessment. Other hormones measured were growth hormone, insulin-like growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), total testosterone, plasma insulin, and C-peptide. Blood glucose and glycosylated hemoglobin were also measured. To assess adrenal reserve, an ACTH stimulation test was performed. The fatigue assessment scale (FAS) was used to evaluate fatigue severity.

RESULTS: Eighty-four adult patients were included. Overall, 40.5% of the patients had at least one endocrine disorder. These included prediabetes (21.4%), low DHEA-S (21.4%), subclinical hypothyroidism (3.6%), non-specific thyroid function abnormality (7.1%), thyroid autoimmunity (7.1%), low testosterone in males (6.6%), and low IGF-1 (3.6%). All patients had normal adrenal reserve. Long-COVID-19 symptoms were present in all patients and the most commonly reported symptom was fatigue (89.3%). The FAS score was higher than normal (≥ 22) in 42.8% of patients. There were no associations between patients' symptoms and hormone levels. Diabetic patients reported confusion (p = 0.020) and hair loss (p = 0.040) more often than non-diabetics.

CONCLUSIONS: The evaluation of endocrine function 3 months after a positive SARS-CoV2 test revealed only subclinical syndromes. The vast majority of patients reported mainly fatigue, among other symptoms, which were unrelated, however, to endocrine function.}, } @article {pmid37996384, year = {2024}, author = {Sunata, K and Miyata, J and Terai, H and Matsuyama, E and Watase, M and Namkoong, H and Asakura, T and Masaki, K and Chubachi, S and Ohgino, K and Kawada, I and Harada, N and Sasano, H and Nakamura, A and Kusaka, Y and Ohba, T and Nakano, Y and Nishio, K and Nakajima, Y and Suzuki, S and Yoshida, S and Tateno, H and Ishii, M and Fukunaga, K}, title = {Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.}, journal = {Allergology international : official journal of the Japanese Society of Allergology}, volume = {73}, number = {2}, pages = {206-213}, doi = {10.1016/j.alit.2023.11.003}, pmid = {37996384}, issn = {1440-1592}, mesh = {Adult ; Female ; Humans ; Middle Aged ; *Asthma/epidemiology ; Cohort Studies ; *COVID-19/epidemiology ; Fatigue/epidemiology ; Japan/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Risk Factors ; Male ; Young Adult ; }, abstract = {BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID.

METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.

RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma.

CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.}, } @article {pmid37995983, year = {2024}, author = {Elmunzer, BJ and Palsson, OS and Forbes, N and Zakaria, A and Davis, C and Canakis, A and Qayed, E and Bick, B and Pawa, S and Tierney, WM and McLeod, CG and Taylor, J and Patel, H and Mendelsohn, RB and Bala, G and Sloan, I and Merchant, AA and Smith, ZL and Sendzischew Shane, MA and Aroniadis, OC and Ordiah, CO and Ruddy, JM and Simren, M and Tack, J and Drossman, D and , }, title = {Prolonged Gastrointestinal Manifestations After Recovery From COVID-19.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {22}, number = {5}, pages = {1098-1107.e3}, doi = {10.1016/j.cgh.2023.11.009}, pmid = {37995983}, issn = {1542-7714}, mesh = {Humans ; *COVID-19/complications/epidemiology/psychology ; Female ; Male ; Middle Aged ; *Gastrointestinal Diseases/etiology/epidemiology ; *Hospitalization/statistics & numerical data ; Aged ; Adult ; SARS-CoV-2 ; Surveys and Questionnaires ; Severity of Illness Index ; Follow-Up Studies ; Cohort Studies ; North America/epidemiology ; }, abstract = {BACKGROUND & AIMS: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19.

METHODS: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12-18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events-Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up.

RESULTS: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P < .0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events-Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events-Revised) was the strongest predictor of GI symptom severity at follow-up.

CONCLUSIONS: In this follow-up survey of patients 12-18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.}, } @article {pmid37995543, year = {2023}, author = {Tudor, L and Harenwall, S and Henderson, R and Bland, AR}, title = {Post-covid-19 syndrome: Self-compassion and psychological flexibility moderate the relationship between physical symptom load and psychosocial impact.}, journal = {Acta psychologica}, volume = {241}, number = {}, pages = {104093}, doi = {10.1016/j.actpsy.2023.104093}, pmid = {37995543}, issn = {1873-6297}, mesh = {Female ; Humans ; *Self-Compassion ; Post-Acute COVID-19 Syndrome ; Empathy ; *COVID-19 ; }, abstract = {Living with persistent physical symptoms of an acute COVID-19 infection has a substantial impact on individuals' everyday lives. The identification of potential therapeutic targets for Post-COVID-19 Syndrome (PCS) or "Long-COVID" that can be utilised to reduce the impact of symptoms, is necessary to support effective rehabilitation. Self-compassion and psychological flexibility are thought to be important constructs to consider when understanding how individuals approach the management of long-term health challenges. The present study investigated the extent to which self-compassion and psychological flexibility moderate the relationship between physical symptoms and their impact on daily life. One-hundred and five participants (91 females) who were living with PCS after an acute COVID-19 infection, completed measures to assess PCS physical symptom prevalence as well as measures to assess impact on daily life, self-compassion and psychological flexibility. Two parallel moderation analyses showed that self-compassion and psychological flexibility significantly moderated the relationships between physical symptom presentation and their psychosocial impact. This research highlights the buffering effects of self-compassion and psychological flexibility and the need to consider these psychological therapeutic targets, as part of PCS multidisciplinary rehabilitation.}, } @article {pmid37995422, year = {2024}, author = {Pérez-López, FR and Blümel, JE and Vallejo, MS and Rodríguez, I and Tserotas, K and Salinas, C and Rodrigues, MA and Rey, C and Ojeda, E and Ñañez, M and Miranda, C and López, M and Díaz, K and Dextre, M and Calle, A and Bencosme, A}, title = {Anxiety but not menopausal status influences the risk of long-COVID-19 syndrome in women living in Latin America.}, journal = {Maturitas}, volume = {180}, number = {}, pages = {107873}, doi = {10.1016/j.maturitas.2023.107873}, pmid = {37995422}, issn = {1873-4111}, mesh = {Female ; Humans ; Latin America/epidemiology ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology/complications ; *COVID-19/epidemiology ; Menopause ; Anxiety/epidemiology ; *Psychological Tests ; Resilience, Psychological ; }, abstract = {OBJECTIVE: To study sociodemographic and clinical factors associated with the long-COVID-19 syndrome among women living in Latin American countries using undirected and directed methods.

METHOD: We studied 347 patients with COVID-19 (confirmed by polymerase chain reaction) living in nine Latin American countries between May 2021 and July 2022, including 70 premenopausal, 48 perimenopausal, and 229 postmenopausal women. We compared the sociodemographic and general health information of women with (n = 164) and without (n = 183) the long-COVID-19 syndrome. They also completed the Connor-Davidson Resilience Scale, the Fear of COVID-19 Scale, the Jenkins Sleep Scale, and the Menopause Rating Scale to define the minimum set of variables for adjustment. We designed a directed acyclic graph (DAG) to identify factors related to the long-COVID-19 syndrome. Data were submitted to categorical logistic regression analyses. Results are reported as means and standard deviations or β-coefficients and 95 % confidence intervals.

RESULTS: Women with long-COVID-19 syndrome had a poor lifestyle, severe menopause symptoms, hypertension, insomnia, depression, anxiety, chronic diseases/conditions, risk of hospitalization, sleep disturbance, and low menopause-related quality of life compared to women without the syndrome. The DAG identified the following long-COVID-19 covariates: age, obesity, anxiety, depression, cancer, lifestyle, smoking, and menstrual status. A multivariable logistic model with these covariates indicated that anxiety is the only factor to be significantly associated with long-COVID-19 syndrome, whereas other covariates were confounding factors. There was no significant influence of menopausal status on the long-COVID-19 syndrome.

CONCLUSION: Among factors selected by the DAG, only anxiety was significantly associated with the long-COVID-19. There was no significant influence of the menopause status on the long-COVID-19 syndrome in the studied population.}, } @article {pmid37992084, year = {2023}, author = {Fatima, S and Ismail, M and Ejaz, T and Shah, Z and Fatima, S and Shahzaib, M and Jafri, HM}, title = {Association between long COVID and vaccination: A 12-month follow-up study in a low- to middle-income country.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0294780}, pmid = {37992084}, issn = {1932-6203}, mesh = {Humans ; Adult ; Middle Aged ; Aged ; *COVID-19/epidemiology/prevention & control ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Vaccination ; Hospitals, University ; }, abstract = {OBJECTIVE: There is a lack of estimates regarding the at-risk population associated with long COVID in Pakistan due to the absence of prospective longitudinal studies. This study aimed to determine the prevalence of long COVID and its association with disease severity and vaccination status of the patient.

DESIGN AND DATA SOURCES: This prospective cohort study was conducted at the Aga Khan University Hospital and recruited patients aged > 18 years who were admitted between February 1 and June 7, 2021. During this time, 901 individuals were admitted, after excluding patients with missing data, a total of 481 confirmed cases were enrolled.

RESULTS: The mean age of the study population was 56.9±14.3 years. Among patients with known vaccination status (n = 474), 19%(n = 90) and 19.2%(n = 91) were fully and partially vaccinated, respectively. Severe/critical disease was present in 64%(n = 312). The mortality rate following discharge was 4.58%(n = 22). Around 18.9%(n = 91) of the population required readmission to the hospital, with respiratory failure (31.8%, n = 29) as the leading cause. Long COVID symptoms were present in 29.9%(n = 144), and these symptoms were more prevalent in the severe/critical (35.5%, n = 111) and unvaccinated (37.9%, n = 105) cohort. The most prominent symptoms were fatigue (26.2%, n = 126) and shortness of breath (24.1%, n = 116), followed by cough (15.2%, n = 73). Vaccinated as compared to unvaccinated patients had lower readmissions (13.8% vs. 21.51%) and post-COVID pulmonary complications (15.4% vs. 24.2%). On multivariable analysis, after adjusting for age, gender, co-morbidity, and disease severity, lack of vaccination was found to be an independent predictor of long COVID with an Odds ratio of 2.42(95% CI 1.52-3.84). Fully and partially vaccinated patients had 62% and 56% reduced risk of developing long COVID respectively.

CONCLUSIONS: This study reports that the patients continued to have debilitating symptoms related to long COVID, one year after discharge, and most of its effects were observed in patients with severe/critical disease and unvaccinated patients.}, } @article {pmid37991964, year = {2023}, author = {Ivantsov, K and Lim, V and Kukes, I and Ternovoy, K and Khripunova, O}, title = {FATIGUE IN PATIENTS WITH LONG COVID.}, journal = {Georgian medical news}, volume = {}, number = {342}, pages = {108-112}, pmid = {37991964}, issn = {1512-0112}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/complications ; Fatigue/etiology ; Dyspnea ; Quality of Life ; }, abstract = {Purpose of the study - to characterize the metabolomic profile in patients with fatigue developing within the Long COVID, during dynamic observation. 24 patients diagnosed with U09.9 "Condition after COVID-19 unspecified" were included in a prospective study. Patients were recommended to engage in physical activity, which included moderate aerobic activity such as walking for 45 minutes a day, three days a week. Clinical assessment by scales (Modified Medical Research Council dyspnea scale; 6-minute walk test; Multidimensional fatigue inventory scale; Barthel index), and determination of metabolomic parameters were performed on days 1 and 14-18 of the study. During the observation period, lactate, fumaric acid, symmetrical dimethylarginine, asymmetric dimethylarginine remained above the reference values. The level of adipic acid returns to normal values. As a result of performing physical activity, such as walking, results on the Modified Medical Research Council scale dyspnea scale, Multidimensional fatigue inventory scale, 6 Minutes Walking Test and Barthel Index improve (p<0,001). Metabolic profile of patients with Long COVID demonstrates the complex of abnormalities at 60 days after the onset of the disease. These metabolic changes are point to possible therapeutic targets for specific pathogenetic pharmacotherapy.}, } @article {pmid37991394, year = {2024}, author = {Thors, V and Bjornsdottir, KL and Love, TJ and Haraldsson, A}, title = {Long COVID in Icelandic Children: A Matched Cohort Study of Nonspecific Symptoms Following SARS-CoV-2 Infection.}, journal = {The Pediatric infectious disease journal}, volume = {43}, number = {3}, pages = {226-233}, doi = {10.1097/INF.0000000000004187}, pmid = {37991394}, issn = {1532-0987}, mesh = {Adolescent ; Humans ; Child ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Iceland/epidemiology ; Quality of Life ; }, abstract = {PURPOSE: Pediatric severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections are usually mild and the mortality rates are low, but concerns have been raised about long-term symptoms that may resemble other postinfectious syndromes. Studies with robust control groups and high response rates have been few.

METHODS: We obtained identifiers for all 837 Icelandic children diagnosed with SARS-CoV-2 by PCR between March 2020 and June 2021 and contacted them by telephone. We asked about 10 physical and mental symptoms being present at least twice weekly for at least 2 months. Participants who reported symptoms were contacted again a year later. For each subject who completed the questionnaire, an age- and sex-matched comparator without SARS-CoV-2 infection was asked to complete the same questionnaire, and the risk difference was calculated.

RESULTS: Responses from 643 cases and 602 comparators were analyzed. Children who had been infected with SARS-CoV-2 were more likely to report one or more symptoms, except for anxiety/depression and sleep disturbances. Fatigue and loss of concentration were evidently more common in cases among teenagers (risk difference: 15%; 95% CI: 7-22% and 15%; 95% CI: 7-23%, respectively). At the second follow-up, close to a third of Long COVID cases had resolved but some participants had developed new persistent symptoms.

CONCLUSION: Symptoms of Long COVID in children are common and impact their quality of life. The importance of further unraveling the pathophysiology of acute and long-term symptoms following SARS-CoV-2 infection in children is vital as well as potential preventive measures.}, } @article {pmid37990967, year = {2023}, author = {Al-Mohammad, A and Kyriacou, AL}, title = {Sinus tachycardia and long-COVID: An opportunity in the challenge.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {53}, number = {4}, pages = {312-313}, doi = {10.1177/14782715231213896}, pmid = {37990967}, issn = {2042-8189}, mesh = {Humans ; *Tachycardia, Sinus ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37990948, year = {2024}, author = {Nugawela, MD and Pinto Pereira, SM and Rojas, NK and McOwat, K and Simmons, R and Dalrymple, E and Ford, T and Garg, S and Hargreaves, D and Semple, MG and Xu, L and Shafran, R and Stephenson, T and , }, title = {Data Resource Profile: the Children and Young People with Long COVID (CLoCk) Study.}, journal = {International journal of epidemiology}, volume = {53}, number = {1}, pages = {}, pmid = {37990948}, issn = {1464-3685}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; //UK Research and Innovation/ ; //National Institute for Health and Care Research/ ; }, mesh = {Child ; Humans ; Adolescent ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37989548, year = {2024}, author = {Calabrese, LH and Mease, PJ}, title = {Improving the nosology of Long COVID: it is not so simple.}, journal = {Annals of the rheumatic diseases}, volume = {83}, number = {1}, pages = {9-11}, doi = {10.1136/ard-2023-224844}, pmid = {37989548}, issn = {1468-2060}, mesh = {Humans ; *COVID-19 ; *Fibromyalgia/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Long COVID is a diagnostic label currently given to those suffering from a poorly understood state of incomplete recovery or who have development of a myriad of medically unexplained symptoms occurring in the wake of infection with SARS CoV-2 that is both poorly understood and controversial. Many of the features of one of the most common clinical endotypes of Long COVID are shared by a condition well familiar to all rheumatologists and one with a large body of epidemiologic, clinical and basic research accrued over many decades namely the syndrome of fibromyalgia. Some have recently suggested that Long COVID may merely be a new name for fibromyalgia and that this diagnosis is indeed the condition that many or most may be suffering from as a post infectious sequela. In this Viewpoint we argue that while the parallels between the clinical syndrome experienced by many of those currently labeled as Long COVID and fibromyalgia are strong we should be not too quick to rename the disorder. We further argue that relabeling Long COVID as fibromyalgia is clinically reductionistic and any such relabeling may be attended by harm in both the design and execution of a future research agenda as well to patients who may be inadvertently and unfortunately pejoritised by such labeling. We further explore the parallels and differences between Long COVID and fibromyalgia and outline areas of needed future research and care.}, } @article {pmid37988366, year = {2023}, author = {McOwat, K and Pinto Pereira, SM and Nugawela, MD and Ladhani, SN and Newlands, F and Stephenson, T and Simmons, R and Semple, MG and Segal, T and Buszewicz, M and Heyman, I and Chalder, T and Ford, T and Dalrymple, E and , and Shafran, R}, title = {The CLoCk study: A retrospective exploration of loneliness in children and young people during the COVID-19 pandemic, in England.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0294165}, pmid = {37988366}, issn = {1932-6203}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Child ; Female ; Adolescent ; *Loneliness ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Retrospective Studies ; England/epidemiology ; }, abstract = {BACKGROUND: During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.

METHODS AND FINDINGS: Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas.

CONCLUSIONS: We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.}, } @article {pmid37988251, year = {2023}, author = {Buck, AM and Deitchman, AN and Takahashi, S and Lu, S and Goldberg, SA and Bodansky, A and Kung, A and Hoh, R and Williams, MC and Kerbleski, M and Maison, DP and Deveau, TM and Munter, SE and Lombardo, J and Wrin, T and Petropoulos, CJ and Durstenfeld, MS and Hsue, PY and Kelly, JD and Greenhouse, B and Martin, JN and Deeks, SG and Peluso, MJ and Henrich, TJ}, title = {The breadth of the neutralizing antibody response to original SARS-CoV-2 infection is linked to the presence of Long COVID symptoms.}, journal = {Journal of medical virology}, volume = {95}, number = {11}, pages = {e29216}, pmid = {37988251}, issn = {1096-9071}, support = {K24 AI174971/AI/NIAID NIH HHS/United States ; K23 AI162249/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; /NH/NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Antibodies, Neutralizing ; COVID-19 Vaccines ; Cross-Sectional Studies ; Pandemics ; SARS-CoV-2 ; Antibodies, Viral ; }, abstract = {The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross-neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected early in the COVID-19 pandemic, before widespread rollout of SARS-CoV-2 vaccines. Cross-sectional regression models adjusted for clinical covariates and longitudinal mixed-effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms, as well as Long COVID phenotypes. We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of Long COVID symptoms. Specifically, we show that, although nAb responses to the original, infecting strain of SARS-CoV-2 were not associated with Long COVID in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of Long COVID and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with Long COVID phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses.}, } @article {pmid37987274, year = {2023}, author = {Sánchez-García, JC and Reinoso-Cobo, A and Piqueras-Sola, B and Cortés-Martín, J and Menor-Rodríguez, MJ and Alabau-Dasi, R and Rodríguez-Blanque, R}, title = {Long COVID and Physical Therapy: A Systematic Review.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {37987274}, issn = {2079-9721}, abstract = {Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, "brain fog", respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies.}, } @article {pmid37987095, year = {2024}, author = {Menzler, K and Mayr, P and Knake, S and Cassel, W and Viniol, C and Reitz, L and Tsalouchidou, PE and Janzen, A and Anschuetz, K and Mross, P and Koehler, U}, title = {Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new-onset sleepiness in some post-COVID patients.}, journal = {European journal of neurology}, volume = {31}, number = {3}, pages = {e16159}, pmid = {37987095}, issn = {1468-1331}, support = {//Hessisches Ministerium für Wissenschaft und Kunst/ ; }, mesh = {Humans ; United States ; Sleepiness ; RNA, Viral ; *COVID-19/complications ; SARS-CoV-2 ; *Sleep Apnea, Obstructive/complications/diagnosis ; *Disorders of Excessive Somnolence/etiology/complications ; Fatigue/complications ; }, abstract = {BACKGROUND AND PURPOSE: Infection with COVID-19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post-COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post-COVID syndrome using polysomnography.

METHODS: Thirty-four patients with post-COVID syndrome and new-onset fatigue and sleepiness after a SARS-CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020).

RESULTS: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long-term treatment of their OSAS and all reported discontinuation of daytime symptoms.

CONCLUSIONS: Post-COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post-COVID syndrome.}, } @article {pmid37986044, year = {2023}, author = {Tufts, J and Guan, N and Zemedikun, DT and Subramanian, A and Gokhale, K and Myles, P and Williams, T and Marshall, T and Calvert, M and Matthews, K and Nirantharakumar, K and Jackson, LJ and Haroon, S}, title = {The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data.}, journal = {BMC primary care}, volume = {24}, number = {1}, pages = {245}, pmid = {37986044}, issn = {2731-4553}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Female ; Aged ; *Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19/epidemiology/therapy ; Referral and Consultation ; Primary Health Care ; Obesity/epidemiology/therapy ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs.

METHODS: Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19.

RESULTS: Based on an analysis of 472,173 patients with COVID-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and reporting of longer-term symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs.

CONCLUSIONS: The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.}, } @article {pmid37985854, year = {2024}, author = {Sievers, BL and Cheng, MTK and Csiba, K and Meng, B and Gupta, RK}, title = {SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".}, journal = {Cellular & molecular immunology}, volume = {21}, number = {2}, pages = {171-183}, pmid = {37985854}, issn = {2042-0226}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; }, abstract = {An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically. The humoral response to SARS-CoV-2 infection has been the focus of intense research, and the role of the innate immune system has received significantly less attention. Here, we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems. We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.}, } @article {pmid37985127, year = {2023}, author = {Pietrzak-Franger, M}, title = {Postdigital health practices: new directions in medical humanities.}, journal = {Medical humanities}, volume = {49}, number = {4}, pages = {503-510}, doi = {10.1136/medhum-2023-012611}, pmid = {37985127}, issn = {1473-4265}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *Humanities ; Forecasting ; Knowledge ; Narration ; }, abstract = {Digitalisation has changed the way we understand and practice health. The recent pandemic has accelerated some of the developments in digital health and brought about modifications in public access to information. Taking this into consideration, this programmatic paper sets the stage for and conceptualises postdigital health practices as a possible field of inquiry within medical humanities. While delineating some central aspects of said practices, I draw attention to their significance in contemporary strategies of knowledge production. Spotlighting online environments as the point of ingress for the analysis of these practices, I propose three possible foci of critical and methodological engagement. By spotlighting the serialisation, multimodality, and transmediality of such environments, I argue, we have a chance to both augment and go beyond the field's long-standing preoccupation with narrative, attend to various strategies of communicating illness experience, and re-frame them within larger questions of systemic inequalities. On this basis, and taking as examples COVID-19 and Long COVID, I sketch some of the directions that future strands of medical humanities may take and some of the questions we still have to ask for the field to overcome its own biases and blind spots.}, } @article {pmid37984917, year = {2023}, author = {Nys, E and Pauwels, S and Ádám, B and Amaro, J and Athanasiou, A and Bashkin, O and Bric, TK and Bulat, P and Caglayan, C and Guseva Canu, I and Cebanu, S and Charbotel, B and Cirule, J and Curti, S and Davidovitch, N and Dopelt, K and Fikfak, MD and Frilander, H and Gustavsson, P and Höper, AC and Kiran, S and Kogevinas, M and Kudász, F and Kolstad, HA and Lazarevic, SB and Macan, J and Majery, N and Marinaccio, A and Mates, D and Mattioli, S and McElvenny, DM and Mediouni, Z and Mehlum, IS and Merisalu, E and Mijakoski, D and Nena, E and Noone, P and Otelea, MR and Pelclova, D and Pranjic, N and Rosso, M and Serra, C and Rushton, L and Sandal, A and Schernhammer, ES and Stoleski, S and Turner, MC and van der Molen, HF and Varga, M and Walusiak-Skorupa, J and Straif, K and Godderis, L}, title = {Recognition of COVID-19 with occupational origin: a comparison between European countries.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {12}, pages = {694-701}, doi = {10.1136/oemed-2022-108726}, pmid = {37984917}, issn = {1470-7926}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Europe/epidemiology ; *Occupational Diseases/epidemiology/therapy ; Occupations ; *Occupational Exposure/adverse effects ; }, abstract = {OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe.

METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022.

RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries.

CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.}, } @article {pmid37984816, year = {2023}, author = {Njøten, KL and Espehaug, B and Magnussen, LH and Jürgensen, M and Kvale, G and Søfteland, E and Aarli, BB and Frisk, B}, title = {Relationship between exercise capacity and fatigue, dyspnea, and lung function in non-hospitalized patients with long COVID.}, journal = {Physiological reports}, volume = {11}, number = {22}, pages = {e15850}, pmid = {37984816}, issn = {2051-817X}, support = {N/A//Bergen Hospital Trust/ ; //Helse i Hardanger/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/complications ; Dyspnea/etiology ; Exercise Test ; Exercise Tolerance ; Fatigue/diagnosis/etiology ; Forced Expiratory Volume ; Lung ; *Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is a global health problem that impairs patients' functional status. More than 200 reported symptoms have been identified where fatigue, dyspnea, and exercise impairment are most common. This study aimed to describe exercise capacity, fatigue, dyspnea, and lung function in previously non-hospitalized patients with long COVID, and examine the relationship between exercise capacity and fatigue, dyspnea, and lung function. Sixty-five patients, 54 women (83%), mean age of 39 standard deviation (12) years, were included and completed spirometry, cardiopulmonary exercise test, stair climbing test (SCT), 30 second sit-to-stand test (30STST), and questionnaires regarding fatigue and dyspnea. Fatigue was reported by 95% of the participants, whereas 65% reported severe fatigue, and 66% reported dyspnea. Mean exercise capacity measured with peak oxygen uptake (V̇O2peak % pred.) was ≥85% in 65% of the participants. Mean forced expiratory volume in 1 s. and forced vital capacity were 96.6 (10.7)% and 100.8 (10.9)%, respectively, while reduced diffusion capacity for carbon monoxide (DLCO) was found in eight participants (13%). Reduced V̇O2peak kg[-1] and increased time on SCT were significantly associated with increased dyspnea and reduced DLCO but not with fatigue, while 30STST was associated with increased fatigue and dyspnea in previously non-hospitalized patients with long COVID.}, } @article {pmid37984511, year = {2024}, author = {Lladós, G and Massanella, M and Coll-Fernández, R and Rodríguez, R and Hernández, E and Lucente, G and López, C and Loste, C and Santos, JR and España-Cueto, S and Nevot, M and Muñoz-López, F and Silva-Arrieta, S and Brander, C and Durà, MJ and Cuadras, P and Bechini, J and Tenesa, M and Martinez-Piñeiro, A and Herrero, C and Chamorro, A and Garcia, A and Grau, E and Clotet, B and Paredes, R and Mateu, L and , }, title = {Vagus nerve dysfunction in the post-COVID-19 condition: a pilot cross-sectional study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {4}, pages = {515-521}, doi = {10.1016/j.cmi.2023.11.007}, pmid = {37984511}, issn = {1469-0691}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Male ; *COVID-19/complications ; Cross-Sectional Studies ; SARS-CoV-2 ; Pilot Projects ; Vagus Nerve ; Post-Acute COVID-19 Syndrome ; Dyspnea ; Tachycardia ; }, abstract = {OBJECTIVES: The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints.

METHODS: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles.

RESULTS: Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35-51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve.

DISCUSSION: Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC.}, } @article {pmid37982248, year = {2023}, author = {Magklara, K and Kyriakopoulos, M}, title = {The impact of the COVID-19 pandemic on children and young people.}, journal = {Psychiatrike = Psychiatriki}, volume = {34}, number = {4}, pages = {265-268}, doi = {10.22365/jpsych.2023.024}, pmid = {37982248}, issn = {1105-2333}, mesh = {Adult ; Female ; Adolescent ; Humans ; Child ; *COVID-19/epidemiology ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; SARS-CoV-2 ; Communicable Disease Control ; }, abstract = {In March 2020, the World Health Organization declared the spread of COVID-19 as a global pandemic, and youth worldwide were suddenly confronted with unprecedented consequences. The first line of concern was related to the direct effect of SARS-CoV-2 viral infection. While severe physical health symptomatology including death following infection was found to be less common in children than in adults,1 long-COVID has been identified in the pediatric population with the most prevalent manifestations involving mood symptoms, sleep difficulties, and fatigue.2 Secondly, the measures against COVID-19 carried their own set of risks. Many governments imposed national lockdowns, schools closed, remote learning started operating and social distancing measures prevented families from visiting public places or meeting people from other households. Isolation, disruption of everyday routines, and a sharp and dramatic decrease in physical activity and social interaction levels became the new reality experienced by children and adolescents of all age groups.3 Cross-sectional community studies on children and adolescents conducted early in the course of the pandemic indicated elevated levels of loneliness, anxiety, and behavioral problems in youth samples, even during the initial phases of the outbreak.4 Systematic reviews of mainly cross-sectional studies that followed indicated a significant rise in clinically significant anxiety and depression symptoms among children and adolescents compared to pre-pandemic levels5 and high prevalence estimates for depression, anxiety, posttraumatic stress symptomatology, and sleep disorders.6 A recent systematic review that included data from 55,000 children and adolescents from many countries of the world (mean age 11.3 years) reported that anxiety (range = 1.8–49.5%), depression (range = 2.2– 63.8%), irritability (range = 16.7–73.2%) and anger (range = 30.0–51.3%) were frequently reported by children and adolescents during the pandemic.7 However, the experience of the pandemic was not homogenous among all youth. Possible risk factors included the presence of mental health problems before the pandemic, excessive exposure to media, and high COVID-19 caseload in the community, while the presence of any kind of family routines and good parent-child communication were identified as protective factors.7 Females and older adolescents were also reported to be at greater risk for adverse mental health outcomes. In most countries, the spread of the infection, on one hand, and the enforcement of lockdowns and other containment measures, on the other, have put health care under tremendous pressure, leaving families with children with mental health disorders with minimal or inadequate support. Nevertheless, differences were also observed within the group of children with psychiatric or developmental disorders diagnosed before the pandemic. Numerous studies that have investigated the impact of the COVID-19 pandemic and related containment measures on children and adolescents with autism spectrum disorders reported a significant increase in parental stress, as well as high levels of anxiety, irritability, hyperactivity, stereotypical behavior, and other behavioral problems among children and adolescents.8 Further studies that investigated the issue of neurodevelopmental disorders showed that the COVID-19 pandemic has disproportionately and adversely affected children with attention-deficit/hyperactivity disorder (ADHD) with a recent meta-analysis pointing to a global increase in ADHD symptoms.9 Finally, early concerns about a possible significant increase in suicidality among youth during the pandemic were followed by contradicting findings from relevant studies. On the whole, though, it is suggested that during the pandemic, as previously, higher rates of suicidal ideation than of suicidal behaviors and suicide events were reported among children and adolescents.10 Similar patterns of mental health difficulties to those described above have also been identified in youth in Greece. During the early stages of the pandemic, one-third (35.1%) of the parents reported that their child’s psychological health was considerably affected,11 while a study of final-year high-school students found that the rates of severe depression and anxiety increased significantly during the lockdown.12 Among children and adolescents with pre-existing mental health problems from different parts of the country, no change was found in mood state scores pre- and post-pandemic onset, while several of their daily behaviors worsened during the lockdown, such as reduced sleep or time spent outdoors.13 Such research findings related to the effects of the COVID-19 pandemic and its containment measures should guide the follow-up of children and young people affected by it and inform the design of effective health strategies and policies in the post-pandemic era with the aim to prevent and mitigate further mental health crises.}, } @article {pmid37981717, year = {2024}, author = {Spiliopoulos, L and Sørensen, AIV and Bager, P and Nielsen, NM and Hansen, JV and Koch, A and Meder, IK and Videbech, P and Ethelberg, S and Hviid, A}, title = {Postacute symptoms 4 months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study.}, journal = {American journal of epidemiology}, volume = {193}, number = {8}, pages = {1106-1114}, pmid = {37981717}, issn = {1476-6256}, support = {//Danish Ministry of Health/ ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Denmark/epidemiology ; Male ; Female ; Middle Aged ; *SARS-CoV-2 ; Adult ; *COVID-19 Vaccines/administration & dosage ; Aged ; *Post-Acute COVID-19 Syndrome ; Immunization, Secondary/statistics & numerical data ; Young Adult ; Adolescent ; Surveys and Questionnaires ; }, abstract = {Postacute symptoms are not uncommon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with pre-Omicron variants. How the Omicron variant and coronavirus disease 2019 (COVID-19) booster vaccination influence the risk of postacute symptoms is less clear. We analyzed data from a nationwide Danish questionnaire study, EFTER-COVID, comprising 36 109 individuals aged ≥15 years who were tested between July 2021 and January 2022, to evaluate the associations of the Omicron variant and COVID-19 booster vaccination with postacute symptoms and new-onset general health problems 4 months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron cases with controls, comparing Omicron cases with Delta cases, and comparing Omicron cases vaccinated with 3 doses with those vaccinated with 2 doses, adjusting for age, sex, body mass index, self-reported chronic diseases, Charlson comorbidity index, health-care occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial postacute symptoms and new-onset health problems in comparison with controls; the largest RD was observed for memory issues (RD = 7.4%; 95% CI, 6.4-8.3). However, risks were generally lower than those in the Delta period, particularly for dysosmia (RD = -15.0%; 95% CI, -17.0 to -13.2) and dysgeusia (RD = -11.2%; 95% CI, -13.2 to -9.5). Booster vaccination was associated with fewer postacute symptoms and new-onset health problems 4 months after Omicron infection as compared with 2 doses of COVID-19 vaccine.}, } @article {pmid37978296, year = {2023}, author = {Kostka, K and Roel, E and Trinh, NTH and Mercadé-Besora, N and Delmestri, A and Mateu, L and Paredes, R and Duarte-Salles, T and Prieto-Alhambra, D and Català, M and Jödicke, AM}, title = {"The burden of post-acute COVID-19 symptoms in a multinational network cohort analysis".}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7449}, pmid = {37978296}, issn = {2041-1723}, mesh = {Humans ; Cohort Studies ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Electronic Health Records ; Reinfection ; }, abstract = {Persistent symptoms following the acute phase of COVID-19 present a major burden to both the affected and the wider community. We conducted a cohort study including over 856,840 first COVID-19 cases, 72,422 re-infections and more than 3.1 million first negative-test controls from primary care electronic health records from Spain and the UK (Sept 2020 to Jan 2022 (UK)/March 2022 (Spain)). We characterised post-acute COVID-19 symptoms and identified key symptoms associated with persistent disease. We estimated incidence rates of persisting symptoms in the general population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential by comparing their frequency in COVID-19 cases vs. matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections.Our study shows that the proportion of COVID-19 cases affected by persistent post-acute COVID-19 symptoms declined over the study period. Risk for altered smell/taste was consistently higher in patients with COVID-19 vs test-negative controls. Persistent symptoms were more common after reinfection than following a first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms.}, } @article {pmid37978232, year = {2024}, author = {Ozawa, T and Kimura, R and Terai, H and Takemura, R and Namkoong, H and Kondo, M and Fukuda, K and Yagi, K and Asakura, T and Masaki, K and Chubachi, S and Miyata, J and Ohgino, K and Kawada, I and Kagyo, J and Odani, T and Kuwahara, N and Nakachi, I and Ishii, M and Sato, Y and Fukunaga, K}, title = {Calcium channel blockers may reduce the development of long COVID in females.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {47}, number = {4}, pages = {934-943}, pmid = {37978232}, issn = {1348-4214}, mesh = {Female ; Humans ; Male ; Alopecia/etiology ; *Calcium Channel Blockers/therapeutic use ; Cohort Studies ; Hypertension/etiology ; *Post-Acute COVID-19 Syndrome/complications/prevention & control ; Adult ; }, abstract = {With the rising numbers of patients infected with severe acute respiratory syndrome coronavirus 2, long coronavirus disease 2019 (COVID-19)-a sequelae of COVID-19-has become a major problem. Different sexes and age groups develop different long COVID symptoms, and the risk factors for long COVID remain unclear. Therefore, we performed subgroup analyses of patients with COVID-19, classifying them into different groups. In this multicenter cohort study, using an original questionnaire, we examined patients (≥18 years old) diagnosed with COVID-19 from November 2020 to March 2022 and hospitalized at participating medical facilities. In total, 1066 patients were registered (361 female, 620 male). Hypertension was the most common comorbidity (n = 344; 32.5%). Females with hypertension were significantly less likely to develop long COVID symptoms than those without hypertension (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27-0.98; p = 0.043). In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03-0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02-0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04-0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05-0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10-0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12-0.93, p = 0.036). Several long COVID symptoms, including alopecia, were significantly negatively associated with Ca channel-blocker administration in female patients with long COVID. Calcium channel blockers may reduce the development of long COVID in females.}, } @article {pmid37977571, year = {2023}, author = {Rimmer, A}, title = {Clinicians with long covid must get financial support, say unions.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2723}, doi = {10.1136/bmj.p2723}, pmid = {37977571}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Labor Unions ; Financial Support ; }, } @article {pmid37977479, year = {2024}, author = {Bai, J and Wang, J}, title = {Modeling long COVID dynamics: Impact of underlying health conditions.}, journal = {Journal of theoretical biology}, volume = {576}, number = {}, pages = {111669}, pmid = {37977479}, issn = {1095-8541}, support = {R15 GM152943/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Population Dynamics ; Vaccination ; }, abstract = {We propose a new mathematical model to investigate the population dynamics of long COVID, with a focus on the impact of chronic health conditions. Our model connects long COVID with the transmission of COVID-19 so as to accurately predict the prevalence of long COVID from the progression of the infection in the host population. The model additionally incorporates the effects of COVID-19 vaccination. We implement the model with data from both the US and the UK to demonstrate the real-world applications of this modeling framework.}, } @article {pmid37977283, year = {2024}, author = {Stephens, MD and Gazmararian, JA and Khakharia, A}, title = {Prevalence and risk factors of post-acute sequelae of COVID-19 among United States Veterans.}, journal = {Annals of epidemiology}, volume = {89}, number = {}, pages = {1-7}, pmid = {37977283}, issn = {1873-2585}, support = {UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Male ; Humans ; Middle Aged ; Aged ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; *Veterans ; Prevalence ; Retrospective Studies ; SARS-CoV-2 ; Risk Factors ; Disease Progression ; }, abstract = {PURPOSE: To better understand Post-Acute Sequelae of COVID-19 (PASC) in the Veteran population, this study aims to determine the prevalence of PASC and identify risk factors associated with its development.

METHODS: This retrospective cohort study included 363,825 Veterans that tested positive for COVID-19 between February 1, 2020, and September 30, 2022. The primary outcome was the development of PASC 30-180 days following an acute infection with SARS-CoV-2. Multivariate logistic regression was utilized to examine factors associated with PASC.

RESULTS: Of the 363,825 Veterans included in the analysis, 164,315 (45%) displayed symptoms of PASC. The Veterans in this analysis were predominantly male, non-Hispanic White, under the age of 65 years old, and lived in an urban residence. The strongest predictors for PASC included Non-Hispanic Black or African American race compared to Non-Hispanic White race (aOR=1.14), being between the ages of 50 and 64 compared to ages 50 and below (aOR=1.80), diabetes (aOR=8.46), and severe acute infection (aOR=1.42).

CONCLUSION: Results demonstrate potential health inequities for vulnerable individuals, as well as increased risk for individuals with pre-existing comorbidities. The prevalence of PASC provides estimates for future health care utilization. The risk factors identified can aid public health interventions to reduce the burden of PASC.}, } @article {pmid37974389, year = {2024}, author = {MacCallum-Bridges, CL and Hirschtick, JL and Allgood, KL and Ryu, S and Orellana, RC and Fleischer, NL}, title = {Cross-sectional population-based estimates of a rural-urban disparity in prevalence of long COVID among Michigan adults with polymerase chain reaction-confirmed COVID-19, 2020-2022.}, journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association}, volume = {40}, number = {2}, pages = {303-313}, doi = {10.1111/jrh.12807}, pmid = {37974389}, issn = {1748-0361}, support = {6 NU50CK000510-02-04/CC/CDC HHS/United States ; 1 NH75OT000078-01-00/CC/CDC HHS/United States ; 6 NU50CK000510-02-04/CC/CDC HHS/United States ; 1 NH75OT000078-01-00/CC/CDC HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Michigan/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; COVID-19 Vaccines ; Cross-Sectional Studies ; Urban Population ; Polymerase Chain Reaction ; COVID-19 Testing ; }, abstract = {PURPOSE: To (1) assess whether residential rurality/urbanicity was associated with the prevalence of 30- or 90-day long COVID, and (2) evaluate whether differences in long COVID risk factors might explain this potential disparity.

METHODS: We used data from the Michigan COVID-19 Recovery Surveillance Study, a population-based probability sample of adults with COVID-19 (n = 4,937). We measured residential rurality/urbanicity using dichotomized Rural-Urban Commuting Area codes (metropolitan, nonmetropolitan). We considered outcomes of 30-day long COVID (illness duration ≥30 days) and 90-day long COVID (illness duration ≥90 days). Using Poisson regression, we estimated unadjusted prevalence ratios (PRs) to compare 30- and 90-day long COVID between metropolitan and nonmetropolitan respondents. Then, we adjusted our model to account for differences between groups in long COVID risk factors (age, sex, acute COVID-19 severity, vaccination status, race and ethnicity, socioeconomic status, health care access, SARS-CoV-2 variant, and pre-existing conditions). We estimated associations for the full study period (Jan 1, 2020-May 31, 2022), the pre-vaccine era (before April 5, 2021), and the vaccine era (after April 5, 2021).

FINDINGS: Compared to metropolitan adults, the prevalence of 30-day long COVID was 15% higher (PR = 1.15 [95% CI: 1.03, 1.29]), and the prevalence of 90-day long COVID was 27% higher (PR = 1.27 [95% CI: 1.09, 1.49]) among nonmetropolitan adults. Adjusting for long COVID risk factors did not reduce disparity estimates in the pre-vaccine era but halved estimates in the vaccine era.

CONCLUSIONS: Our findings provide evidence of a rural-urban disparity in long COVID and suggest that the factors contributing to this disparity changed over time as the sociopolitical context of the pandemic evolved and COVID-19 vaccines were introduced.}, } @article {pmid37974068, year = {2023}, author = {Kenny, G and McCann, K and O'Brien, C and O'Broin, C and Tinago, W and Yousif, O and O'Gorman, T and Cotter, AG and Lambert, JS and Feeney, ER and de Barra, E and Sadlier, C and Landay, A and Doran, P and Savinelli, S and Mallon, PWG and , }, title = {Impact of vaccination and variants of concern on long COVID clinical phenotypes.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {804}, pmid = {37974068}, issn = {1471-2334}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; Cohort Studies ; Prospective Studies ; Vaccination ; Chest Pain ; Phenotype ; }, abstract = {BACKGROUND: Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters.

METHODS: In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms.

RESULTS: A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p = 0.004) and palpitations (12% vs 32% p < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms.

CONCLUSION: This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.}, } @article {pmid37973731, year = {2023}, author = {Schumacher, B}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {165}, number = {20}, pages = {18}, doi = {10.1007/s15006-023-3137-z}, pmid = {37973731}, issn = {1613-3560}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37972000, year = {2023}, author = {Meakleartmongkol, T and Tangpanithandee, S and Vanavivit, N and Jiso, A and Pongchaikul, P and Kirdlarp, S and Khemawoot, P and Nathisuwan, S}, title = {Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0293866}, pmid = {37972000}, issn = {1932-6203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Drug Interactions ; Databases, Factual ; Cytochrome P-450 Enzyme System ; Electronics ; }, abstract = {Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were selected from Thailand's National List of Essential Medicine 2022 for potential DDI analysis by Micromedex and Drugs.com. From these databases, 488 potential DDIs were identified. There were 271 and 434 DDI pairs based on Micromedex and Drugs.com, respectively. Among these DDIs, 77 pairs were labeled as contraindicated or major by both databases. The most common mechanisms for these serious interactions are cytochrome P450 (CYP) inhibition (45%), CYP induction (19%), and QT interval prolongation (7.8%). Based on Fleiss' kappa (0.073), there was only slight agreement of the DDI severity classifications between these two databases. In conclusion, a large number of potential DDIs were detected among frequently prescribed medications for long COVID. Health care providers should be aware of these DDIs, particularly those that are deemed as contraindicated or major. These DDIs are most likely to cause significant adverse events in patients with long COVID because polypharmacy is common.}, } @article {pmid37971795, year = {2023}, author = {Sousa, F and de Araujo, LN and de Oliveira, TSO and Gomes, MC and Ferreira, G and Aben-Athar, C and da Silva, SED and Cruz Ramos, AM and Rodrigues, DP}, title = {Demographic, Clinical, and Quality of Life Profiles of Older People With Diabetes During the COVID-19 Pandemic: Cross-Sectional Study.}, journal = {JMIR formative research}, volume = {7}, number = {}, pages = {e49817}, pmid = {37971795}, issn = {2561-326X}, abstract = {BACKGROUND: Diabetes mellitus, one of the main diseases that affects the Brazilian population older than 60 years, is defined as a divergent group of metabolic disorders that present a high level of glycemia (hyperglycemia), causing damage to various organs and systems of the body, including the heart, kidneys, eyes, and nervous system. It is believed that in 2025, in Brazil alone, there will be more than 18.5 million individuals diagnosed with diabetes mellitus. Therefore, it is important to know the individuals' quality of life in the context of life and culture.

OBJECTIVE: This study aimed to assess the demographic, clinical, and quality of life profiles of older adults with diabetes during the COVID-19 pandemic in a university hospital complex in the northern Amazon region.

METHODS: We conducted a cross-sectional, exploratory, noninterventional, descriptive, and analytical study using a nonrandom sample of 54 older people diagnosed with diabetes mellitus at the geriatrics outpatient clinic of the medium and high complexity university hospital in the western Brazilian Amazon between 2020 and 2022. We used 3 instruments, namely, a sociodemographic questionnaire, a clinical conditions questionnaire, and Diabetes-39. Qualitative data were described using absolute and relative frequencies. The Kolmogorov-Smirnov normality test was applied, and the z test was used for inferential analysis. SPSS software (version 27) was used for data analysis, and the significance level was 5%.

RESULTS: Of the 54 interviewees, the majority were women, married, retired, and had a good quality of life. Of these, 48.1% (n=26) were infected by COVID-19, 61.5% (n=16) of whom progressed to long COVID, presenting with fatigue or muscle weakness. As for the quality of life, the "social overload" (P<.001) and "sexual functioning" (P<.001) dimensions had with low scores compared to the "energy and mobility" (P=.005), "diabetes control" (P<.001), and "anxiety and worry" (P<.001) dimensions. Quality of life was negatively impacted in the "anxiety and worry" dimension. Among those affected by COVID-19, most progressed to long COVID; however, there was a lack of data on this theme in the population of older people with diabetes.

CONCLUSIONS: The majority of interviewees progressed to long COVID, with their quality of life negatively impacted in the "anxiety and worry" dimension, reflecting that health actions prioritizing mental health should be implemented by health professionals.}, } @article {pmid37970745, year = {2023}, author = {Zeng, G and Zhang, Z and Wang, L and Li, J}, title = {Risk factors of long COVID 6-12 months after infection with the Omicron variant among nonhospitalized patients.}, journal = {Journal of medical virology}, volume = {95}, number = {11}, pages = {e29235}, doi = {10.1002/jmv.29235}, pmid = {37970745}, issn = {1096-9071}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Risk Factors ; }, } @article {pmid37968601, year = {2023}, author = {Hoeggerl, AD and Nunhofer, V and Lauth, W and Badstuber, N and Held, N and Zimmermann, G and Grabmer, C and Weidner, L and Jungbauer, C and Lindlbauer, N and Neureiter, H and Ortner, T and Flamm, M and Osterbrink, J and Rohde, E and Laner-Plamberger, S}, title = {Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {800}, pmid = {37968601}, issn = {1471-2334}, support = {20204-WISS/225/197-2019//Salzburger Landesregierung (WISS 2025)/ ; }, mesh = {Adult ; Humans ; Herpesvirus 4, Human ; *Epstein-Barr Virus Infections/diagnosis ; SARS-CoV-2/genetics ; Antigens, Viral ; Neopterin ; *COVID-19 ; Antibodies, Viral ; Immunoglobulin M ; Immunoglobulin G ; DNA ; }, abstract = {PURPOSE: Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.

METHODS: The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed.

RESULTS: Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.

CONCLUSION: Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.}, } @article {pmid37967846, year = {2024}, author = {Violi, F and Harenberg, J and Pignatelli, P and Cammisotto, V}, title = {COVID-19 and Long-COVID Thrombosis: From Clinical and Basic Science to Therapeutics.}, journal = {Thrombosis and haemostasis}, volume = {124}, number = {4}, pages = {286-296}, doi = {10.1055/s-0043-1776713}, pmid = {37967846}, issn = {2567-689X}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; SARS-CoV-2 ; Anticoagulants/therapeutic use ; *Thrombosis/drug therapy ; *Communicable Diseases ; }, abstract = {Coronavirus infectious disease-19 (COVID-19) is a pandemic characterized by serious lung disease and thrombotic events in the venous and circulation trees, which represent a harmful clinical sign of poor outcome. Thrombotic events are more frequent in patients with severe disease requiring intensive care units and are associated with platelet and clotting activation. However, after resolution of acute infection, patients may still have clinical sequelae, the so-called long-COVID-19, including thrombotic events again in the venous and arterial circulation. The mechanisms accounting for thrombosis in acute and long COVID-19 have not been fully clarified; interactions of COVID-19 with angiotensin converting enzyme 2 or toll-like receptor family or infection-induced cytokine storm have been suggested to be implicated in endothelial cells, leucocytes, and platelets to elicit clotting activation in acute as well in chronic phase of the disease. In acute COVID-19, prophylactic or full doses of anticoagulants exert beneficial effects even if the dosage choice is still under investigation; however, a residual risk still remains suggesting a need for a more appropriate therapeutic approach. In long COVID-19 preliminary data provided useful information in terms of antiplatelet treatment but definition of candidates for thrombotic prophylaxis is still undefined.}, } @article {pmid37967057, year = {2023}, author = {Ishizuka, K and Miyagami, T and Tsuchida, T and Saita, M and Ohira, Y and Naito, T}, title = {Online search interest in long-term symptoms of coronavirus disease 2019 during the COVID-19 pandemic in Japan: Infodemiology study using the most visited search engine in Japan.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0294261}, pmid = {37967057}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Search Engine ; Post-Acute COVID-19 Syndrome ; Pandemics ; Japan/epidemiology ; Infodemiology ; }, abstract = {Prolonged symptoms that occur after COVID-19 (long-COVID) vary from mild, which do not interfere with daily life, to severe, which require long-term social support. This study assessed the secular trend in online searches on long-COVID in Japan. We conducted an observational study using data provided by Yahoo! JAPAN on the monthly search volume of query terms related to long-COVID from January 2020 to December 2022, including the search volume of the query "コロナ" (long-COVID in Japanese). The number of new cases of COVID-19 by month was used as a control for search trends, and the symptoms retrieved in conjunction with long-COVID were compared. Trends in online searches for each symptom of long-COVID were analyzed. The symptoms of long-COVID were classified according to "Component 1-Symptoms and Complaints" of the International Classification of Primary Care, 2nd edition (ICPC-2). Interest in long-COVID increased in response to peaks in the number of new cases of COVID-19 in Japan. The most frequent symptom searches with long-COVID were hair loss/baldness (3,530, 21,400, and 33,600 searches in 2020, 2021, and 2022, respectively), cough (340, 7,900 and 138,910 searches in 2020, 2021, and 2022, respectively), disturbance of smell/taste (230, 13,340, and 44,160 searches in 2020, 2021, and 2022, respectively), and headache (580, 6,180, and 42,870 searches in 2020, 2021, and 2022, respectively). In addition, the ranking of interest in "weakness/tiredness, general" in long-COVID increased each year (not in the top 10 in 2020, seventh in 2021, and second in 2022), and the absolute number of searches also increased. To our knowledge, this is the first study to investigate secular trends in online interest in long-COVID in the world. Continued monitoring of online interest in long-COVID is necessary to prepare for a possible increase in the number of patients with long-COVID.}, } @article {pmid37965614, year = {2023}, author = {Bourdas, DI and Bakirtzoglou, P and Travlos, AK and Andrianopoulos, V and Zacharakis, E}, title = {Analysis of a comprehensive dataset: Influence of vaccination profile, types, and severe acute respiratory syndrome coronavirus 2 re-infections on changes in sports-related physical activity one month after infection.}, journal = {Data in brief}, volume = {51}, number = {}, pages = {109723}, pmid = {37965614}, issn = {2352-3409}, abstract = {This dataset was created with the primary objective of elucidating the intricate relationship between the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) re-infections and the pre-illness vaccination profile and types concerning alterations in sports-related physical activity (PA) after SARS-CoV-2 infection among adults. A secondary objective encompassed a comprehensive statistical analysis to explore the influence of three key factors-namely, Vaccination profile, Vaccination types, and Incidence of SARS-CoV-2 re-infections-on changes in PA related to exercise and sports, recorded at two distinct time points: one to two weeks prior to infection and one month after the last SARS-CoV-2 infection. The sample population (n = 5829), drawn from Hellenic territory, adhered to self-inclusion and exclusion criteria. Data collection spanned from February to March 2023 (a two-month period), involving the utilization of the Active-Q (an online, interactive questionnaire) to automatically assess weekly habitual sports-related PA among adults both before and after their last SARS-CoV-2 infection. The questionnaire also captured participant characteristics, pre-illness vaccination statuses (i.e., unvaccinated, partially vaccinated, fully vaccinated, and vaccine types), and occurrences of SARS-CoV-2 re-infections. The dataset sheds light on two noteworthy phenomena: (i) the intricate interplay between post-acute SARS-CoV-2 infection and a decline in sports-related physical activity (-27.6 ± 0.6%, 95%CI: -26.1 - -29.1), influenced by the pre-illness vaccination profile factor (p = 0.040); and (ii) the divergence in sports-related physical activity decline between partially vaccinated (-38.2 ± 0.7%, 95%CI: -35.3 - -41.1, p = 0.031) and fully vaccinated respondents (-19.2 ± 0.5%, 95%CI: -17.2 - -21.2). These phenomena underscore the imperative for tailored interventions and further investigation to promote the resumption of physical activity and mitigate long-term repercussions. Furthermore, this dataset enriches our understanding of the dynamics of sports-related physical activity and provides valuable insights for public health initiatives aiming to address the consequences of COVID-19 on sports-related physical activity levels. Consequently, this cross-sectional dataset is amenable to a diverse array of analytical methodologies, including univariate and multivariate analyses, and holds potential relevance for researchers, leaders in the sports and medical sectors, and policymakers, all of whom share a vested interest in fostering initiatives directed at reinstating physical activity and mitigating the enduring ramifications of post-acute SARS-CoV-2 infection.}, } @article {pmid37965507, year = {2023}, author = {Sharif, N and Sharif, N and Khan, A and Halawani, IF and Alzahrani, FM and Alzahrani, KJ and Díez, IT and Vargas, DLR and Castilla, AGK and Parvez, AK and Dey, SK}, title = {Prevalence and impact of long COVID-19 among patients with diabetes and cardiovascular diseases in Bangladesh.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1222868}, pmid = {37965507}, issn = {2296-2565}, mesh = {Humans ; *Cardiovascular Diseases/epidemiology ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Prevalence ; Bangladesh/epidemiology ; Risk Factors ; *COVID-19/epidemiology ; *Diabetes Mellitus/epidemiology ; Chronic Disease ; }, abstract = {INTRODUCTION: Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh.

METHODS: We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival.

RESULTS: COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79-4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients.

DISCUSSION: Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh.}, } @article {pmid37965093, year = {2023}, author = {Neto, RBD and Reis, LFF and Ferreira, AS and Alexandre, DJA and de Almeida, RS}, title = {Hospital admission is associated with disability and late musculoskeletal pain in individuals with long COVID.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1186499}, pmid = {37965093}, issn = {2673-6861}, abstract = {BACKGROUND: The acute clinical repercussions of SARS-CoV-2 infection have been widely studied. However, the possible late repercussions of long COVID have not yet been well defined in the literature.

OBJECTIVES: To identify the presence of pain and musculoskeletal disability in patients with Long COVID and also to identify predictive factors for pain intensity in this population.

METHODS: In this cross-sectional and retrospective observational study individuals with Long COVID symptoms were included. It was collected musculoskeletal disability measures, data from patient-related outcome measures and variables from a COVID-19 outpatient service database. Associations and sub-group analyses were performed considering the variables pain, disability and hospitalization. Linear regression was performed to identify predictive factors for pain intensity in Long COVID patients.

RESULTS: We evaluated 195 patients and most of them (57%) presented musculoskeletal pain in one area of the body. Pain sub-group presented worse disability indices and worse clinical course during hospitalization. Hospitalized patients presented worse disability indices comparing to non-hospitalized. Significant correlations were found between pain and days of non-invasive oxygen support (r = 0.21; p = 0.003); days in intensive care unit (r = 0.22; p = 0.002) and days in invasive mechanical ventilation (r = 0.35; p = 0.001). Hospitalized individuals showed a higher chance of presenting late musculoskeletal pain (OR = 1.42: 95%CI 1.09-2.04). Days in intensive care unit (β = 0,234: P = 0,001) and days in invasive mechanical ventilation (β = 0.764: P = 0.001) were predictors of pain intensity [F(2,192) = 18.559; R[2] = 0.231; p = 0.001].

CONCLUSION: Individuals with Long COVID presented musculoskeletal pain and disability. Hospitalized patients showed a greater chance of having musculoskeletal pain. Days in intensive care unit and days in invasive mechanical ventilation were predictors of late musculoskeletal pain intensity.}, } @article {pmid37964554, year = {2023}, author = {Pierre, V and Draica, F and Di Fusco, M and Yang, J and Nunez-Gonzalez, S and Kamar, J and Lopez, S and Moran, MM and Nguyen, J and Alvarez, P and Cha-Silva, A and Gavaghan, M and Yehoshua, A and Stapleton, N and Burnett, H}, title = {The impact of vaccination and outpatient treatment on the economic burden of Covid-19 in the United States omicron era: a systematic literature review.}, journal = {Journal of medical economics}, volume = {26}, number = {1}, pages = {1519-1531}, doi = {10.1080/13696998.2023.2281882}, pmid = {37964554}, issn = {1941-837X}, mesh = {Humans ; *COVID-19/prevention & control ; Financial Stress ; Post-Acute COVID-19 Syndrome ; Outpatients ; Vaccination ; *Vaccines ; }, abstract = {AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era.

MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria.

RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters.

LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed.

CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.}, } @article {pmid37964352, year = {2023}, author = {Wang, S and Peng, H and Chen, F and Liu, C and Zheng, Q and Wang, M and Wang, J and Yu, H and Xue, E and Chen, X and Wang, X and Fan, M and Qin, X and Wu, Y and Li, J and Ye, Y and Chen, D and Hu, Y and Wu, T}, title = {Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases.}, journal = {Human genomics}, volume = {17}, number = {1}, pages = {101}, pmid = {37964352}, issn = {1479-7364}, support = {No. BX2021021//China Postdoctoral Science Foundation/ ; No. 2020CXB009//Fujian Provincial Health Technology Project/ ; No. 2021J01352//Natural Science Foundation of Fujian Province, China/ ; No. 8123066//Key Project of Natural Science Funds of China/ ; No. 81872695//National Natural Science Foundation of China/ ; No. 201502006//Special Fund for Health Scientific Research in Public Welfare/ ; }, mesh = {Humans ; Bayes Theorem ; Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; *Coronary Disease/epidemiology/genetics ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide/genetics ; Genetic Loci ; Genome-Wide Association Study ; }, abstract = {BACKGROUND: Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.

METHODS: By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs).

FINDINGS: Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18-0.19) to 0.23 (95% CI 0.23-0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks.

INTERPRETATION: Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of 'Long COVID-19.'}, } @article {pmid37964338, year = {2023}, author = {Watase, M and Miyata, J and Terai, H and Sunata, K and Matsuyama, E and Asakura, T and Namkoong, H and Masaki, K and Yagi, K and Ohgino, K and Chubachi, S and Kawada, I and Mochimaru, T and Satomi, R and Oyamada, Y and Kobayashi, K and Hirano, T and Inoue, T and Lee, H and Sugihara, K and Omori, N and Sayama, K and Mashimo, S and Makino, Y and Kaido, T and Ishii, M and Fukunaga, K}, title = {Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese cohort study.}, journal = {Respiratory research}, volume = {24}, number = {1}, pages = {283}, pmid = {37964338}, issn = {1465-993X}, support = {JPMJPR21R7//JST PRESTO/ ; 20CA2054//Health Labor Science Special Research Project/ ; JP20nk0101612//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Sputum ; SARS-CoV-2 ; Cohort Studies ; Japan/epidemiology ; Cough/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID.

METHODS: Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.

RESULTS: At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan-Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months.

CONCLUSIONS: In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.}, } @article {pmid37963962, year = {2023}, author = {Vélez-Santamaría, R and Fernández-Solana, J and Méndez-López, F and Domínguez-García, M and González-Bernal, JJ and Magallón-Botaya, R and Oliván-Blázquez, B and González-Santos, J and Santamaría-Peláez, M}, title = {Functionality, physical activity, fatigue and quality of life in patients with acute COVID-19 and Long COVID infection.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19907}, pmid = {37963962}, issn = {2045-2322}, mesh = {Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19 ; Surveys and Questionnaires ; Fatigue ; Exercise ; }, abstract = {A prominent feature of COVID-19, both in the short and long term, is the reduction in quality of life (QoL) due to low functionality scores and the presence of fatigue, which can hinder daily activities. The main objective of this study is to compare the functional status, level of physical activity, fatigue, and QoL of patients with Long COVID to other COVID-19 patients who did not develop persistent illness, and to determine whether there is a relationship between these variables and QoL. A cross-sectional study was conducted with 170 participants who had been infected with COVID-19 or had developed Long COVID. The main variables studied were functionality, physical activity, QoL and fatigue, measured using the PostCOVID-19 Functional Status Scale (PCFS), International Physical Activity Questionnaire (IPAQ), Short Form 12 (SF-12), and Fatigue Severity Scale (FSS). The main findings show a significant relationship (p < 0.001) between reduced functionality, lower physical activity levels, increased fatigue severity, and poorer QoL in Long COVID patients. Furthermore, these variables are also related to worse QoL, but only functional status predicts it. In conclusion, our results have shown highly significant correlations between the group with COVID-19 and Long COVID regarding functional status, level of physical activity, QoL, and fatigue.}, } @article {pmid37962719, year = {2023}, author = {Cheston, K and Cenedese, ML and Woods, A}, title = {The Long or the Post of It? Temporality, Suffering, and Uncertainty in Narratives Following COVID-19.}, journal = {The Journal of medical humanities}, volume = {}, number = {}, pages = {}, pmid = {37962719}, issn = {1573-3645}, support = {217840/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 209513/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Long COVID affects millions of individuals worldwide but remains poorly understood and contested. This article turns to accounts of patients' experiences to ask: What might narrative be doing both to long COVID and for those who live with the condition? What particular narrative strategies were present in 2020, as millions of people became ill, en masse, with a novel virus, which have prevailed three years after the first lockdowns? And what can this tell us about illness and narrative and about the importance of literary critical approaches to the topic in a digital, post-pandemic age? Through a close reading of journalist Lucy Adams's autobiographical accounts of long COVID, this article explores the interplay between individual illness narratives and the collective narrativizing (or making) of an illness. Our focus on temporality and suffering knits together the phenomenological and the social with the aim of opening up Adams's narrative and ascertaining a deeper understanding of what it means to live with the condition. Finally, we look to the stories currently circulating around long COVID and consider how illness narratives-and open, curious, patient-centered approaches to them-might shape medicine, patient involvement, and critical medical humanities research.}, } @article {pmid37961575, year = {2023}, author = {Ravkov, EV and Williams, ESCP and Elgort, M and Barker, AP and Planelles, V and Spivak, AM and Delgado, JC and Lin, L and Hanley, TM}, title = {Reduced Monocyte Proportions and Responsiveness in Convalescent COVID-19 Patients.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.25.563806}, pmid = {37961575}, issn = {2692-8205}, abstract = {The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and COVID-19 suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We investigated the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and non-classical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients and uninfected control subjects. We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF-α and IL-6 in response to LPS stimulation, than those from uninfected controls. In conclusion, SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.}, } @article {pmid37961239, year = {2023}, author = {Peluso, MJ and Swank, ZN and Goldberg, SA and Lu, S and Dalhuisen, T and Borberg, E and Senussi, Y and Luna, MA and Song, CC and Clark, A and Zamora, A and Lew, M and Viswanathan, B and Huang, B and Anglin, K and Hoh, R and Hsue, PY and Durstenfeld, MS and Spinelli, MA and Glidden, DV and Henrich, TJ and Daniel Kelly, J and Deeks, SG and Walt, DR and Martin, JN}, title = {Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37961239}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; K23 AI134327/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity.

METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa[®] (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens.

RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection.

CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.}, } @article {pmid37960844, year = {2023}, author = {Huynh, DHT and Nguyen, DT and Nguyen, TST and Nguyen, BAH and Huynh, ATT and Nguyen, VNN and Tran, DQ and Hoang, TNN and Tran, HD and Liem, DT and Vo, GV and Nguyen, MN}, title = {Insights into the epidemiology and clinical aspects of post-COVID-19 conditions in adult.}, journal = {Chronic illness}, volume = {}, number = {}, pages = {17423953231209377}, doi = {10.1177/17423953231209377}, pmid = {37960844}, issn = {1745-9206}, abstract = {OBJECTIVES: While most individuals infected with COVID-19 recover completely within a few weeks, some continue to experience lingering symptoms. This study was conducted to identify and describe the clinical and subclinical manifestations of adult patients from the long-term effects of COVID-19.

METHODS: The study analyzed 205 medical records of inpatients (age ≥ 16 years, ≥ 4 weeks post-COVID-19 recovery, and a negative SARS-CoV-2 status at enrollment) at Thong Nhat Hospital, Vietnam, from 6 September 2021 to 26 August 2022, using R language software.

RESULTS: The majority of patients hospitalized with long COVID-19 symptoms (92.68%) had normal consciousness. The most common symptoms on admission were fatigue (59.02%), dyspnea (52.68%), and cough (42.93%). In total, 80% of patients observed respiratory symptoms, primarily dyspnea, while 42.44% reported neurological symptoms, with sleep disturbance being the most common. Noticeably, 42.93% of patients experienced respiratory failure in the post-COVID-19 period, resembling acute respiratory distress syndrome.

DISCUSSION: These findings provide crucial insights into the epidemiology, clinical, and subclinical aspects of post-COVID-19 conditions, shedding light on the prevalence of common symptoms and the demographic distribution of affected patients. Understanding these manifestations is vital for patient well-being, improved clinical practice, and targeted healthcare planning, potentially leading to better patient care, management, and future interventions.}, } @article {pmid37960295, year = {2023}, author = {Carvalho, MCDC and Araujo, JKCP and da Silva, AGCL and da Silva, NS and de Araújo, NK and Luchessi, AD and Ribeiro, KDDS and Silbiger, VN}, title = {Retinol Levels and Severity of Patients with COVID-19.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, pmid = {37960295}, issn = {2072-6643}, support = {001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; Vitamin A ; *COVID-19/epidemiology ; *Vitamin A Deficiency/complications/epidemiology ; Case-Control Studies ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {The new coronavirus infection represents a serious threat to global health and economies. In this sense, it is paramount to know the nutritional factors that may be related to the prognosis of the disease. Evidence shows that vitamin A may play an important preventive and therapeutic role in supporting respiratory infections as in COVID-19. The aim of our study was to evaluate the association of vitamin A (retinol) status with the prognosis of the disease. A case-control study from a cohort study was conducted in Brazil between May and October 2020. The study population was chosen by convenience, consisting of participants diagnosed with COVID-19. Recruitment was carried out using different approaches, including through dissemination on social media and in four hospitals in the city of Natal/RN, Brazil, recruiting participants from the COVID-19 ward and hospitalized participants who tested positive for the disease. The participants were allocated into two groups according to severity, with a group of mild (n = 88) or critical (n = 106) patients and compared to a control group (selected before the pandemic, n = 46). The extraction of retinol serum was performed and analyzed using the high-performance liquid chromatography method (HPLC). The retinol level was calculated in mmol/L, and levels below 0.7 μmol/L (20 µg/dL) were considered to be a vitamin A deficiency. Our findings suggest that the participants with mild and critical COVID-19 had lower retinol levels compared to the healthy controls (p = 0.03). In addition, milder cases of COVID-19 were associated with increased symptoms and prolonged symptoms after 90 days since the beginning of infection. However, the survival analysis showed no association with higher cases of death among participants with vitamin A deficiency (p = 0.509). More studies are needed to understand how nutritional status, including vitamin A levels, can influence prognosis and is a risk factor for the development of long COVID syndrome.}, } @article {pmid37959356, year = {2023}, author = {Shmueli, E and Bar-On, O and Amir, B and Mei-Zahav, M and Stafler, P and Levine, H and Steuer, G and Rothschild, B and Tsviban, L and Amitai, N and Dotan, M and Chodick, G and Prais, D and Ashkenazi-Hoffnung, L}, title = {Pulmonary Evaluation in Children with Post-COVID-19 Condition Respiratory Symptoms: A Prospective Cohort Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {21}, pages = {}, pmid = {37959356}, issn = {2077-0383}, abstract = {Background: Studies on post-COVID-19 condition (PCC) in adults have shown deterioration in pulmonary function tests (PFTs), mainly a diffusion limitation. Among the pediatric population, data are scarce. Aim: To characterize PFTs in children with PCC, including changes over time. Methods: A prospective longitudinal study of children with defined PCC and respiratory complaints who were referred to a designated multidisciplinary clinic from 11/2020 to 12/2022. Results: Altogether, 184 children with a mean age of 12.4 years (SD 4.06) were included. A mild obstructive pattern was demonstrated in 19/170 (11%) at presentation, as indicated by spirometry and/or positive exercise challenge test and/or reversibility post bronchodilators, only three had a previous diagnosis of asthma. Lung volumes and diffusion were normal in all but one patient (1/134, 0.7%). Exhaled nitric oxide levels were elevated in 32/144 (22%). A total of 33 children who had repeated PFTs had normal or near-normal PFTs on follow-up testing, including seven (21.2%) who had mild obstructive PFTs at presentation. Multivariate analysis identified older age [OR 1.36 (95% CI:1.07-1.75)], specific imaging findings (prominent bronchovascular markings (OR 43.28 (95% CI: 4.50-416.49)), and hyperinflation (OR 28.42, 95% CI: 2.18-370.84)] as significant predictors of an obstructive pattern on PFTs. Conclusions: In children with PCC and respiratory symptoms, the most common impairment was a mild obstructive pattern; most were without a history of asthma. Improvement was witnessed in long-term follow-up. In contrast to the adult population, no diffusion limitation was found. Empirical periodic inhaler therapy may be considered in children with factors associated with PFT abnormalities.}, } @article {pmid37959205, year = {2023}, author = {Mooren, JM and Garbsch, R and Schäfer, H and Kotewitsch, M and Waranski, M and Teschler, M and Schmitz, B and Mooren, FC}, title = {Medical Rehabilitation of Patients with Post-COVID-19 Syndrome-A Comparison of Aerobic Interval and Continuous Training.}, journal = {Journal of clinical medicine}, volume = {12}, number = {21}, pages = {}, pmid = {37959205}, issn = {2077-0383}, abstract = {INTRODUCTION: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective in improving physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training.

METHODS: A total of 110 PCS patients (49.3 ± 11.8 years; 38% women; time after infection = 260.2 ± 127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week; 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT; load = 60%, relief = 30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD; n = 96) to evaluate overall training effectiveness.

RESULTS: Training participation was comparable between the groups, with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8 ± 12.1% for W at VT1; 3.1 ± 10.0% for VO2 at VT1; 5.5 ± 14.7% for O2 pulse at VT1; 7.5 ± 15.0% for W at VO2peak; 2.7 ± 11.0% for VO2peak and 4.6 ± 12.4% for O2 pulse at VO2peak (all p < 0.05) with no significant differences between groups (p > 0.05). Both groups showed reduced levels of fatigue, anxiety, and depression as well as improved quality of life and wellbeing (all p < 0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients.

CONCLUSION: PCS patients benefit from aerobic endurance training performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. The results for PCS patients are comparable to the guideline-based rehabilitation of CAD patients.}, } @article {pmid37958264, year = {2023}, author = {Luchian, ML and Higny, J and Benoit, M and Robaye, B and Berners, Y and Henry, JP and Colle, B and Xhaët, O and Blommaert, D and Droogmans, S and Motoc, AI and Cosyns, B and Gabriel, L and Guedes, A and Demeure, F}, title = {Unmasking Pandemic Echoes: An In-Depth Review of Long COVID's Unabated Cardiovascular Consequences beyond 2020.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {21}, pages = {}, pmid = {37958264}, issn = {2075-4418}, abstract = {At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.}, } @article {pmid37957515, year = {2024}, author = {Gomaa, AA and Abdel-Wadood, YA and Thabet, RH and Gomaa, GA}, title = {Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy.}, journal = {Inflammopharmacology}, volume = {32}, number = {1}, pages = {249-271}, pmid = {37957515}, issn = {1568-5608}, mesh = {Animals ; Humans ; Chronic Disease ; *COVID-19 ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Receptors, Calcitriol ; SARS-CoV-2 ; *Vitamin D/pharmacology/therapeutic use ; *Vitamins/pharmacology/therapeutic use ; }, abstract = {Nearly four years after its first appearance, and having gone from pandemic to endemic, the SARS-CoV-2 remains out of control globally. The purpose of this study was to evaluate the clinical efficacy of vitamin D (VD) in COVID-19 and long COVID-19, explain the discrepancy in clinical outcomes and highlight the potential impact of metformin on VD efficacy in recent articles. Articles from January 2022 to August 2023 were selected for this review. The objective of this study was achieved by reviewing, analyzing, and discussing articles demonstrating (1) the mechanism of action of VD (2) observational or randomized clinical trials (RCTs) that support or not the beneficial clinical effects of VD in COVID-19 or long COVID. (3) genetic and non-genetic reasons for the variation in the effects of VD. Articles were collected from electronic databases such as PubMed, Scopus, MEDLINE, Google Scholar, Egyptian Knowledge Bank, Science Direct, and Cochrane Database of Systematic Reviews. Twenty three studies conducted in vitro or in animal models indicated that VD may act in COVID-19 through protecting the respiratory system by antimicrobial peptide cathelicidins, reducing lung inflammation, regulating innate and adaptive immune functions and up regulation of autophagy gene activity. Our review identified 58 clinical studies that met the criteria. The number of publications supporting a beneficial clinical activity of VD in treating COVID-19 was 49 (86%), including 12 meta-analyses. Although the total patients included in all articles was 14,071,273, patients included in publications supporting a beneficial role of VD in COVID-19 were 14,029,411 (99.7%). Collectively, extensive observational studies indicated a decisive relationship between low VD levels and the severity of COVID-19 and mortality outcomes. Importantly, evidence from intervention studies has demonstrated the effectiveness of VD supplements in treating COVID-19. Furthermore, the results of 4 observational studies supported the beneficial role of VD in alleviating symptoms of long COVID-19 disease. However, eight RCTs and one meta-analysis of RCTs may contain low-grade evidence against a beneficial role of VD in COVID-19. Twenty-five articles have addressed the association between VDR and DBP genetic polymorphisms and treatment failure of VD in COVID-19. Impaired VDR signaling may underlie the variability of VD effects as non-genetic mechanisms. Interestingly, in recent studies, metformin has a beneficial therapeutic role in COVID-19 and long COVID-19, possibly by improving AMPK signaling of the VDR and enhancing the efficacy of the VD. In conclusion, evidence has been significantly strengthened over the past 18 months, with several meta-analyses and RCTs reporting conclusive beneficial effects of VD supplementation against COVID-19 and highlighting metformin to improve VDR sensitivity and efficacy in treating COVID-19 and long COVID-19.}, } @article {pmid37956938, year = {2023}, author = {Dhaka, P and Singh, A and Choudhary, S and Peddinti, RK and Kumar, P and Sharma, GK and Tomar, S}, title = {Mechanistic and thermodynamic characterization of antiviral inhibitors targeting nucleocapsid N-terminal domain of SARS-CoV-2.}, journal = {Archives of biochemistry and biophysics}, volume = {750}, number = {}, pages = {109820}, doi = {10.1016/j.abb.2023.109820}, pmid = {37956938}, issn = {1096-0384}, mesh = {Humans ; *SARS-CoV-2 ; Antiviral Agents/pharmacology/chemistry ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Nucleocapsid/metabolism ; Thermodynamics ; RNA ; Molecular Docking Simulation ; }, abstract = {The nucleocapsid (N) protein of SARS-CoV-2 plays a pivotal role in encapsulating the viral genome. Developing antiviral treatments for SARS-CoV-2 is imperative due to the diminishing immunity of the available vaccines. This study targets the RNA-binding site located in the N-terminal domain (NTD) of the N-protein to identify the potential antiviral molecules against SARS-CoV-2. A structure-based repurposing approach identified the twelve high-affinity molecules from FDA-approved drugs, natural products, and the LOPAC[1280] compound libraries that precisely bind to the RNA binding site within the NTD. The interaction of these potential antiviral agents with the purified NTD protein was thermodynamically characterized using isothermal titration calorimetry (ITC). A fluorescence-based plate assay to assess the RNA binding inhibitory activity of small molecules against the NTD has been employed, and the selected compounds exhibited significant RNA binding inhibition with calculated IC50 values ranging from 8.8 μM to 15.7 μM. Furthermore, the antiviral efficacy of these compounds was evaluated using in vitro cell-based assays targeting the replication of SARS-CoV-2. Remarkably, two compounds, Telmisartan and BMS-189453, displayed potential antiviral activity against SARS-CoV-2, with EC50 values of approximately 1.02 μM and 0.98 μM, and a notable selective index of >98 and > 102, respectively. This study gives valuable insight into developing therapeutic interventions against SARS-CoV-2 by targeting the N-protein, a significant effort given the global public health concern posed due to the virus re-emergence and long COVID-19 disease.}, } @article {pmid37956731, year = {2024}, author = {Datta, BK and Coughlin, SS and Fazlul, I and Pandey, A}, title = {COVID-19 and health care-related financial toxicity in the United States: Evidence from the 2022 National Health Interview Survey.}, journal = {American journal of infection control}, volume = {52}, number = {4}, pages = {392-399}, doi = {10.1016/j.ajic.2023.11.004}, pmid = {37956731}, issn = {1527-3296}, mesh = {Adult ; Humans ; United States/epidemiology ; *Financial Stress ; Health Expenditures ; COVID-19 Testing ; Pandemics ; *COVID-19/epidemiology ; }, abstract = {BACKGROUND: Despite the common perception of the socioeconomic burden of the COVID-19 pandemic, quantification of the relationship between COVID-19 and indicators of health care-related financial toxicity in the general population has been limited. This study aimed to provide estimates of these relationships in a nationally representative sample of the US adult population.

METHODS: Using the data on 27,480 adults from the 2022 National Health Interview Survey, we fitted multivariable logistic regression models to assess the differential risks of financial toxicity as manifested by the financial hardship in paying medical bills, delayed and forgone medical care, and medication nonadherence, by COVID-19 diagnosis, severity, and duration of symptoms.

RESULTS: We found that compared to individuals not having COVID-19, individuals with severe symptoms of COVID-19 were 1.86, 1.50, 1.76, and 1.77 times more likely to experience financial hardship, delay medical care, forgo medical care, and skip/delay/take less medication, respectively. Similarly, individuals with symptoms lasting for 3 or more months were 1.94, 1.65, 1.87, and 2.20 times more likely to experience these measures of financial toxicity, respectively.

CONCLUSIONS: The estimates of the relationship between COVID-19 and financial toxicity will facilitate effective communications for policy actions aimed at alleviating the burden of the COVID-19 pandemic.}, } @article {pmid37955681, year = {2024}, author = {Ruzicka, M and Ibarra Fonseca, GJ and Sachenbacher, S and Heimkes, F and Grosse-Wentrup, F and Wunderlich, N and Benesch, C and Pernpruner, A and Valdinoci, E and Rueb, M and Uebleis, AO and Karch, S and Bogner, J and Mayerle, J and von Bergwelt-Baildon, M and Subklewe, M and Heindl, B and Stubbe, HC and Adorjan, K}, title = {Substantial differences in perception of disease severity between post COVID-19 patients, internists, and psychiatrists or psychologists: the Health Perception Gap and its clinical implications.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {2015-2024}, pmid = {37955681}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/psychology ; Male ; Female ; Middle Aged ; *Psychiatry ; *Severity of Illness Index ; Adult ; Quality of Life ; Aged ; Patient Reported Outcome Measures ; Psychology ; Internal Medicine ; Psychiatrists ; }, abstract = {Patient-reported outcome measures (PROMs) such as the Numeric Pain Rating Scale (NPRS) or Likert scales addressing various domains of health are important tools to assess disease severity in Post COVID-19 (PC) patients. By design, they are subjective in nature and prone to bias. Our findings reveal substantial differences in the perception of disease severity between patients (PAT), their attending internists (INT) and psychiatrists/psychologists (PSY). Patients rated almost all aspects of their health worse than INT or PSY. Most of the differences were statistically highly significant. The presence of fatigue and mood disorders correlated negatively with health perception. The physical health section of the WHO Quality of Life Assessment (WHOQoL-BREF) and Karnofsky index correlated positively with overall and mental health ratings by PAT and INT. Health ratings by neither PAT, PSY nor INT were associated with the number of abnormal findings in diagnostic procedures. This study highlights how strongly perceptions of disease severity diverge between PC patients and attending medical staff. Imprecise communication, different experiences regarding health and disease, and confounding psychological factors may explain these observations. Discrepancies in disease perception threaten patient-physician relationships and pose strong confounders in clinical studies. Established scores (e.g., WHOQoL-BREF, Karnofsky index) may represent an approach to overcome these discrepancies. Physicians and psychologists noting harsh differences between a patient's and their own perception of the patient's health should apply screening tools for mood disorders (i.e., PHQ-9, WHOQoL-BREF), psychosomatic symptom burden (SSD-12, FCV-19) and consider further psychological evaluation. An interdisciplinary approach to PC patients remains imperative. Trial Registration Number & Date of Registration: DRKS00030974, 22 Dec 2022, retrospectively registered.}, } @article {pmid37954002, year = {2023}, author = {Mateu, L and Tebe, C and Loste, C and Santos, JR and Lladós, G and López, C and España-Cueto, S and Toledo, R and Font, M and Chamorro, A and Muñoz-López, F and Nevot, M and Vallejo, N and Teis, A and Puig, J and Fumaz, CR and Muñoz-Moreno, JA and Prats, A and Estany-Quera, C and Coll-Fernández, R and Herrero, C and Casares, P and Garcia, A and Clotet, B and Paredes, R and Massanella, M}, title = {Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study.}, journal = {The Lancet regional health. Europe}, volume = {33}, number = {}, pages = {100724}, pmid = {37954002}, issn = {2666-7762}, abstract = {BACKGROUND: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or "Long COVID". The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown.

METHODS: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach.

FINDINGS: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC.

INTERPRETATION: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems.

FUNDING: Fundació Lluita contra les Infeccions.}, } @article {pmid37953922, year = {2023}, author = {Luo, YS and Zhang, K and Cheng, ZS}, title = {Absence of Association between a Long COVID and Severe COVID-19 Risk Variant of FOXP4 and Lung Cancer.}, journal = {Frontiers in genetics}, volume = {14}, number = {}, pages = {1258829}, pmid = {37953922}, issn = {1664-8021}, } @article {pmid37953820, year = {2023}, author = {Bosworth, ML and Shenhuy, B and Walker, AS and Nafilyan, V and Alwan, NA and O'Hara, ME and Ayoubkhani, D}, title = {Risk of New-Onset Long COVID Following Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2: A Community-Based Cohort Study.}, journal = {Open forum infectious diseases}, volume = {10}, number = {11}, pages = {ofad493}, pmid = {37953820}, issn = {2328-8957}, abstract = {BACKGROUND: Little is known about the risk of long COVID following reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We estimated the likelihood of new-onset, self-reported long COVID after a second SARS-CoV-2 infection, compared to a first infection.

METHODS: We included UK COVID-19 Infection Survey participants who tested positive for SARS-CoV-2 between 1 November 2021 and 8 October 2022. The primary outcome was self-reported long COVID 12-20 weeks after each infection. Separate analyses were performed for those <16 years and ≥16 years. We estimated adjusted odds ratios (aORs) for new-onset long COVID using logistic regression, comparing second to first infections, controlling for sociodemographic characteristics and calendar date of infection, plus vaccination status in participants ≥16 years of age.

RESULTS: Overall, long COVID was reported by those ≥16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those aged <16 years were 1.0% and 0.6%. The aOR for long COVID after second compared to first infections was 0.72 (95% confidence interval [CI], .63-.81) for those ≥16 years and 0.93 (95% CI, .57-1.53) for those <16 years.

CONCLUSIONS: The risk of new-onset long COVID after a second SARS-CoV-2 infection is lower than that after a first infection for persons aged ≥16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset long COVID after a second infection, with around 1 in 40 of those aged ≥16 years and 1 in 165 of those <16 years reporting long COVID after a second infection.}, } @article {pmid37953801, year = {2023}, author = {Marwaha, B}, title = {Role of Tau protein in long COVID and potential therapeutic targets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1280600}, pmid = {37953801}, issn = {2235-2988}, mesh = {Animals ; Humans ; Rats ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; *tau Proteins/metabolism ; Tauopathies/diagnosis/drug therapy/metabolism ; }, abstract = {INTRODUCTION: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

PATHOPHYSIOLOGY: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies. Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies. Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.}, } @article {pmid37953471, year = {2024}, author = {Berto, CG and Kotton, CN}, title = {The Other Pandemic From the Pandemic: A Higher Frequency of Long COVID After Omicron in Kidney Transplant Recipients.}, journal = {Transplantation}, volume = {108}, number = {4}, pages = {841-842}, doi = {10.1097/TP.0000000000004859}, pmid = {37953471}, issn = {1534-6080}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Kidney Transplantation/adverse effects ; Pandemics ; *COVID-19/epidemiology ; Transplant Recipients ; }, } @article {pmid37953468, year = {2024}, author = {Amorim, CEN and Cazetta, GS and Cristelli, MP and Requião-Moura, LR and da Silva, ER and Pinheiro Vale, L and Brito, MMP and Bronzo, T and Nakamura, MR and Tedesco-Silva, H and Medina-Pestana, J}, title = {Long COVID Among Kidney Transplant Recipients Appears to Be Attenuated During the Omicron Predominance.}, journal = {Transplantation}, volume = {108}, number = {4}, pages = {963-969}, doi = {10.1097/TP.0000000000004858}, pmid = {37953468}, issn = {1534-6080}, support = {2021/13680-6//Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP)/ ; }, mesh = {Adult ; Humans ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cohort Studies ; *Kidney Transplantation/adverse effects ; Myalgia ; Prospective Studies ; SARS-CoV-2 ; Transplant Recipients ; }, abstract = {BACKGROUND: Omicron variant has been associated with milder cases of COVID-19 among kidney transplant recipients. However, little is known about postacute sequelae, referred to as Long COVID.

METHODS: Prospective, single-center cohort study investigating prevalence and risk factors for Long COVID among kidney transplant recipients during the omicron predominance in Brazil. The analysis included adult patients with confirmed SARS-CoV-2 infection between January 5, 2022, and July 18, 2022, were alive, had a functioning kidney transplant 3 mo after symptom onset, and answered a telephonic survey about physical complains of Long COVID.

RESULTS: From the 1529 eligible, 602 (39%) patients responded the survey. Sixteen percent reported a previous SARS-CoV-2 infection, and 85% had been fully vaccinated. The prevalence of Long COVID was 52%, with the most common complaints being weakness (46%), myalgia (41%), dizziness (33%), and headache (31%). Among employed patients, 94% were able to resume their normal work activities. In multivariable analysis, female gender (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.51-3.02; P  < 0.0001), previous SARS-CoV-2 infection (HR, 3.55; 95% CI, 1.91-6.60; P  < 0.0001), fatigue (HR, 2.32; 95% CI, 1.18-4.55; P  = 0.014), myalgia (HR, 1.48; 95% CI, 1.03-2.15; P  = 0.036) during the acute phase, and hospitalization because of COVID-19 (HR, 1.71; 95% CI, 1.06-2.76; P  = 0.028) were independently associated with Long COVID.

CONCLUSIONS: In the "omicron era," Long COVID among kidney transplant recipients exhibited milder characteristics and had a less significant impact on their ability to resume normal life activities. The risk factors for persistent symptoms were similar to those observed in the general population except for the vaccination status, underscoring the importance of closer monitoring in special subgroups.}, } @article {pmid37952347, year = {2023}, author = {Pooladgar, P and Sakhabakhsh, M and Soleiman-Meigooni, S and Taghva, A and Nasiri, M and Darazam, IA}, title = {The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {118}, number = {}, pages = {168-174}, doi = {10.1016/j.jocn.2023.09.005}, pmid = {37952347}, issn = {1532-2653}, mesh = {Humans ; Donepezil/therapeutic use ; Iran ; *Quality of Life ; *COVID-19/complications ; Executive Function ; Memory Disorders/drug therapy/etiology ; }, abstract = {BACKGROUND: Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment.

METHODS: A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis.

RESULTS: The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals.

CONCLUSION: While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment.

TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).}, } @article {pmid37951998, year = {2023}, author = {Congdon, S and Narrowe, Z and Yone, N and Gunn, J and Deng, Y and Nori, P and Cowman, K and Islam, M and Rikin, S and Starrels, J}, title = {Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {19688}, pmid = {37951998}, issn = {2045-2322}, mesh = {Adult ; Humans ; *COVID-19 ; COVID-19 Drug Treatment ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Ritonavir/therapeutic use ; SARS-CoV-2 ; Chest Pain ; Antiviral Agents/therapeutic use ; }, abstract = {We conducted a retrospective cohort study to assess whether treatment with nirmatrelvir/ritonavir was associated with a reduced risk of long COVID. We enrolled 500 adults with confirmed SARS-CoV-2 who were eligible for nirmatrelvir/ritonavir; 250 who took nirmatrelvir/ritonavir and 250 who did not. The primary outcome was the development of one or more of eleven prespecified long COVID symptoms, assessed through a structured telephone interview four months after the positive SARS-CoV-2 test. Multivariable logistic regression models controlled for age, sex, race/ethnicity, chronic conditions, and COVID-19 vaccination status. We found that participants who took nirmatrelvir/ritonavir were no less likely to develop long COVID symptoms, compared to those who did not take the medication (44% vs. 49.6%, p = 0.21). Taking nirmatrelvir/ritonavir was associated with a lower odds of two of the eleven long COVID symptoms, brain fog (OR 0.58, 95% CI 0.38-0.88) and chest pain/tightness (OR 0.51, 95% CI 0.28-0.91). Our finding that treatment with nirmatrelvir/ritonavir was not associated with a lower risk of developing long COVID is different from prior studies that obtained data only from electronic medical records.}, } @article {pmid37951572, year = {2024}, author = {Theoharides, TC and Twahir, A and Kempuraj, D}, title = {Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {132}, number = {4}, pages = {440-454}, doi = {10.1016/j.anai.2023.10.032}, pmid = {37951572}, issn = {1534-4436}, mesh = {Humans ; Mast Cells ; Neuroinflammatory Diseases ; *Autism Spectrum Disorder ; Post-Acute COVID-19 Syndrome ; Autonomic Nervous System ; *Postural Orthostatic Tachycardia Syndrome ; }, abstract = {Mast cells (MC) are ubiquitous in the body, and they are critical for not only in allergic diseases but also in immunity and inflammation, including having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome. The evidence indicates that there is a possible association between these conditions and diseases associated with MC activation. There is no effective treatment for any form of these conditions other than minimizing symptoms. Given the many ways MC could be activated and the numerous mediators released, it would be important to develop ways to inhibit stimulation of MC and the release of ANS-relevant mediators.}, } @article {pmid37951314, year = {2023}, author = {Piskac Zivkovic, N and Mutvar, A and Kuster, D and Lucijanic, M and Ljilja Posavec, A and Cvetkovic Kucic, D and Lalic, K and Vergles, M and Udovicic, M and Barsic, B and Rudan, D and Luksic, I and Lang, IM and Skoro-Sajer, N}, title = {Longitudinal analysis of chest Q-SPECT/CT in patients with severe COVID-19.}, journal = {Respiratory medicine}, volume = {220}, number = {}, pages = {107461}, doi = {10.1016/j.rmed.2023.107461}, pmid = {37951314}, issn = {1532-3064}, mesh = {Humans ; SARS-CoV-2 ; Tomography, Emission-Computed, Single-Photon/methods ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Lung/diagnostic imaging ; Tomography, X-Ray Computed/methods ; Dyspnea ; Ferritins ; *Pulmonary Embolism ; }, abstract = {INTRODUCTION: Patients with COVID-19 have an increased risk for microvascular lung thrombosis. In order to evaluate the type and prevalence of perfusion defects, we performed a longitudinal analysis of combined perfusion single-photon emission and low-dose computed tomography (Q-SPECT/CT scan) in patients with COVID-19 pneumonia.

METHODS: Consecutive patients with severe COVID-19 (B.1.1.7 variant SARS-CoV-2) and respiratory insufficiency underwent chest Q-SPECT/CT during hospitalization, and 3 months after discharge. At follow-up (FU), Q-SPECT/CT were analyzed and compared with pulmonary function tests (PFT), blood analysis (CRP, D-dimers, ferritin), modified Medical Research Council (mMRC) dyspnea scale, and high-resolution CT scans (HRCT). Patients with one or more segmental perfusion defects outside the area of inflammation (PDOI) were treated with anticoagulation until FU.

RESULTS: At baseline, PDOI were found in 50 of 105 patients (47.6 %). At FU, Q-SPECT/CT scans had improved significantly (p < 0.001) and PDOI were recorded in 14 of 77 (18.2 %) patients. There was a significant correlation between mMRC score and the number of segmental perfusion defects (r = 0.511, p < 0.001), and a weaker correlation with DLCO (r = -0.333, p = 0.002) and KCO (r = -0.373, p = 0.001) at FU. Neither corticosteroid therapy nor HRCT results showed an influence on Q-SPECT/CT changes (p = 0.94, p = 0.74). CRP, D-Dimers and ferritin improved but did not show any association with the FU Q-SPECT/CT results (p = 0.08).

CONCLUSION: Segmental mismatched perfusion defects are common in severe COVID-19 and are correlated with the degree of dyspnea. Longitudinal analyses of Q-SPECT/CT scans in severe COVID-19 may help understand possible mechanisms of long COVID and prolonged dyspnea.}, } @article {pmid37950846, year = {2023}, author = {Ocampo, FF and Promsena, P and Chan, P}, title = {Update on Central Nervous System Effects of the Intersection of HIV-1 and SARS-CoV-2.}, journal = {Current HIV/AIDS reports}, volume = {20}, number = {6}, pages = {345-356}, pmid = {37950846}, issn = {1548-3576}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; *HIV-1 ; *HIV Infections/complications/drug therapy ; *HIV Seropositivity ; Central Nervous System ; }, abstract = {PURPOSE OF REVIEW: Research has shown myriad neurologic and mental health manifestations during the acute and subsequent stages of COVID-19 in people with HIV (PWH). This review summarizes the updates on central nervous system (CNS) outcomes following SARS-CoV-2 infection in PWH and highlight the existing knowledge gaps in this area.

RECENT FINDINGS: Studies leveraging electronic record systems have highlighted the excess risk of developing acute and lingering neurological complications of COVID-19 in PWH compared to people without HIV (PWoH). However, there is a notable scarcity of neuroimaging as well as blood and cerebrospinal fluid (CSF) marker studies that can confirm the potential synergy between these two infections, particularly in PWH receiving suppressive antiretroviral therapy. Considering the unclear potential interaction between SARS-CoV-2 and HIV, clinicians should remain vigilant regarding new-onset or worsening neurological symptoms in PWH following COVID-19, as they could be linked to either infection.}, } @article {pmid37950097, year = {2024}, author = {Özlek, B and Akın, F and Altun, İ}, title = {Long COVID and myocardial ischemia: how aware are we?.}, journal = {The international journal of cardiovascular imaging}, volume = {40}, number = {1}, pages = {207-208}, pmid = {37950097}, issn = {1875-8312}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Predictive Value of Tests ; *Myocardial Ischemia/diagnostic imaging ; *Coronary Artery Disease ; }, } @article {pmid37949826, year = {2023}, author = {Al-Aly, Z}, title = {Long COVID and its cardiovascular implications: a call to action.}, journal = {European heart journal}, volume = {44}, number = {47}, pages = {5001-5003}, doi = {10.1093/eurheartj/ehad723}, pmid = {37949826}, issn = {1522-9645}, support = {//US Department of Veterans Affairs/ ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Cardiovascular System ; SARS-CoV-2 ; Heart ; }, } @article {pmid37948194, year = {2023}, author = {Grand, RJ}, title = {SARS-CoV-2 and the DNA damage response.}, journal = {The Journal of general virology}, volume = {104}, number = {11}, pages = {}, pmid = {37948194}, issn = {1465-2099}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Genomic Instability ; DNA Damage ; }, abstract = {The recent coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by respiratory distress, multiorgan dysfunction and, in some cases, death. The virus is also responsible for post-COVID-19 condition (commonly referred to as 'long COVID'). SARS-CoV-2 is a single-stranded, positive-sense RNA virus with a genome of approximately 30 kb, which encodes 26 proteins. It has been reported to affect multiple pathways in infected cells, resulting, in many cases, in the induction of a 'cytokine storm' and cellular senescence. Perhaps because it is an RNA virus, replicating largely in the cytoplasm, the effect of SARS-Cov-2 on genome stability and DNA damage responses (DDRs) has received relatively little attention. However, it is now becoming clear that the virus causes damage to cellular DNA, as shown by the presence of micronuclei, DNA repair foci and increased comet tails in infected cells. This review considers recent evidence indicating how SARS-CoV-2 causes genome instability, deregulates the cell cycle and targets specific components of DDR pathways. The significance of the virus's ability to cause cellular senescence is also considered, as are the implications of genome instability for patients suffering from long COVID.}, } @article {pmid37947962, year = {2023}, author = {Hira, R and Karalasingham, K and Baker, JR and Raj, SR}, title = {Autonomic Manifestations of Long-COVID Syndrome.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {12}, pages = {881-892}, pmid = {37947962}, issn = {1534-6293}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/complications/epidemiology ; *Autonomic Nervous System Diseases/epidemiology/etiology ; Autonomic Nervous System ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology ; }, abstract = {PURPOSE OF REVIEW: Long-COVID is a novel condition emerging from the COVID-19 pandemic. Long-COVID is characterized by symptoms commonly seen in autonomic disorders including fatigue, brain fog, light-headedness, and palpitations. This article will critically evaluate recent findings and studies on Long-COVID and its physiological autonomic manifestations.

RECENT FINDINGS: Studies have reported on the prevalence of different symptoms and autonomic disorders in Long-COVID cohorts. Autonomic nervous system function, including both the parasympathetic and sympathetic limbs, has been studied using different testing techniques in Long-COVID patients. While numerous mechanisms may contribute to Long-COVID autonomic pathophysiology, it is currently unclear which ones lead to a Long-COVID presentation. To date, studies have not tested treatment options for autonomic disorders in Long-COVID patients. Long-COVID is associated with autonomic abnormalities. There is a high prevalence of clinical autonomic disorders among Long-COVID patients, with limited knowledge of the underlying mechanisms and the effectiveness of treatment options.}, } @article {pmid37947537, year = {2023}, author = {Monier, D and Bonjean, P and Carcasset, P and Moulin, M and Pozzetto, B and Botelho-Nevers, E and Fontana, L and Pelissier, C}, title = {Factors Contributing to Delayed Return to Work among French Healthcare Professionals Afflicted by COVID-19 at a Hospital in the Rhône-Alpes Region, 2021.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {21}, pages = {}, pmid = {37947537}, issn = {1660-4601}, mesh = {Humans ; Infant, Newborn ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Asthenia ; Return to Work ; SARS-CoV-2 ; Personnel, Hospital ; Hospitals, University ; Delivery of Health Care ; }, abstract = {COVID-19 is an emerging disease whose impact on the return to work of hospital staff is not yet known. This study was aimed at evaluating the prevalence of delayed return to work associated with medical, personal, and professional factors in hospital staff who tested positive for COVID-19 during the second epidemic wave. A descriptive, analytical observational study was conducted. The source population consisted of all staff of a French University Hospital Center who had an RT-PCR test or an antigenic test positive for SARS-CoV-2 during the period from 6 September to 30 November 2020. A delayed return to work was defined as a return to work after a period of at least 8 days of eviction, whereas before the eviction period decided by the French government was 14 days. Data collection was carried out through an anonymous online self-questionnaire. The participation rate was 43% (216 participants out of 502 eligible subjects). Moreover, 40% of the staff had a delayed return to work, and 24% of them reported a delayed return to work due to persistent asthenia. Delayed return to work was significantly associated with age, fear of returning to work, and persistent asthenia, but the number of symptoms lasting more than 7 days was the only factor that remained significantly associated after multivariate analysis. From this study, it appears that interest in identifying the number of persistent symptoms as a possible indicator of delayed work emerges. Moreover, persistent asthenia should be given special attention by practitioners to detect a possible long COVID.}, } @article {pmid37947228, year = {2023}, author = {Shaikh, NA and Fathima, S and Siddique, A and Abufool, L and Atef Demian, B and Mobushar, JA and Pradeep, R}, title = {Duration and aetiology of extended hospitalization among COVID-19 patients in United Arab Emirates.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {29}, number = {10}, pages = {783-788}, doi = {10.26719/emhj.23.106}, pmid = {37947228}, issn = {1687-1634}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; United Arab Emirates/epidemiology ; COVID-19 Drug Treatment ; Hospitalization ; Retrospective Studies ; }, abstract = {BACKGROUND: A retrospective review of the early stages of the COVID-19 pandemic in 2020 and the challenges faced by hospitals is essential in the post-pandemic era of 2022.

AIM: To identify the reasons for prolonged hospitalization after recovery for COVID-19 patients in the United Arab Emirates.

METHODS: This was a retrospective observational study of 150 (18.75%) patients with prolonged hospitalization in a tertiary hospital in Dubai from 1 April to 1 July 2020. Data was obtained from the electronic medical records of the hospital. Continuous variables are reported as mean and standard deviation, and categorical variables are reported as numbers and percentages.

RESULTS: The mean duration of hospitalization was 48.5 (9-272) days, with an interquartile range (IQR) of 22 days. The mean duration of extended stay was 27.5 (2-231) days, with an IQR of 17 days. The common reasons for prolonged hospitalization were mandatory isolation 28% (n = 62), hospital-acquired infections 17% (n = 37), acute respiratory distress syndrome 15% (n = 32), myopathy/neuropathy 14% (n = 31), pulmonary fibrosis requiring oxygen supplementation 14% (n = 31), and completion of COVID-19 treatment 12% (n = 25).

CONCLUSION: To make optimal use of available hospital resources, reasons that directly or indirectly contributed to the prolonged hospitalization of patients should be considered and addressed during future pandemics or disease outbreaks.}, } @article {pmid37947104, year = {2023}, author = {Rodríguez Onieva, A and Vallejo Basurte, C and Fernández Bersabé, A and Camacho Cerro, L and Valverde Bascón, B and Muriel Sanjuan, N and Soto Castro, CA and García Morales, V and Piedra Ruiz, F and Hidalgo Requena, A}, title = {Clinical Characterization of the Persistent COVID-19 Symptoms: A Descriptive Observational Study in Primary Care.}, journal = {Journal of primary care & community health}, volume = {14}, number = {}, pages = {21501319231208283}, pmid = {37947104}, issn = {2150-1327}, mesh = {Adult ; Male ; Female ; Humans ; Middle Aged ; *COVID-19/epidemiology ; SARS-CoV-2 ; Headache/epidemiology/etiology ; Fatigue/epidemiology/etiology ; Dyspnea/epidemiology/etiology ; Primary Health Care ; }, abstract = {INTRODUCTION: Evidence and clinical experience suggest that there are a range of signs of health issues that affect patients who have recovered from acute COVID-19 infection. This condition is commonly referred to as "persistent COVID-19," which is not connected with the severity of the disease. We have identified the prevalence and clinical-epidemiological characteristics of patients with COVID-19 and persistent symptoms treated in primary care centers. This is a descriptive observational study conducted between December 2020 and May 2022, the data were collected from digitized medical records and interviewing 1542 individuals with laboratory-confirmed SARS-CoV-2 infection. These patients were clinically followed for up to 1 year, based on the prevalence of symptoms. When stratifying by the risk of developing persistent COVID-19, 37.09% of the patients exhibited risk factors, with age (over 60 years) and cardiovascular risk factors predominating. The obtained prevalence of persistent COVID-19 at 90 days was 12.39%, with a slight predominance in females (55%) and a mean age of 45.8 years. The most affected systems were the cardiovascular, respiratory, and psychoneurological systems, with predominant symptoms of fatigue (41.88%), dyspnea (32.46%), and headache (14.66%), among others. The average duration of persistent symptoms was 178 days, equivalent to 6 months. In conclusion, over 10% of patients who recover from acute SARS-CoV-2 infection developed long-term consequences.

OBJECTIVE: To measure the prevalence and clinical-epidemiological characteristics of individuals diagnosed with COVID-19 and persistent symptoms treated in primary care centers in Área Sanitaria Sur de Córdoba (Spain) between December 2020 and May 2022.

METHODS: A retrospective observational study of the population of Área Sanitaria Sur de Córdoba was developed between December 2020 and May 2022. The scope of the study was 1542 individuals, and the prevalence of patients diagnosed with COVID-19 and persistent symptoms was determined based on laboratory-confirmed cases, randomly selected from adults who had progressed beyond the acute phase of the disease. All data were managed by the Área Sanitaria Sur de Córdoba (Spain).

RESULTS: The risk factor of exhibiting one or more risk factors associated with developing persistent COVID-19 is 37.09%. The obtained prevalence of persistent COVID-19 at 90 days is 12.39%, it is higher in females (55%) than males and the mean age was 45.8 years. The most affected systems were the cardiovascular, respiratory, and psychoneurological systems, with predominant symptoms of fatigue (41.88%), dyspnea (32.46%), and headache (14.66%), among others.

CONCLUSIONS: Results confirm that more than 10% of individuals recovering from acute SARS-CoV-2 infection showed long-term consequences and the observed persistent symptom duration was 178 days on average.}, } @article {pmid37946190, year = {2023}, author = {Gasión, V and Barceló-Soler, A and Beltrán-Ruiz, M and Hijar-Aguinaga, R and Camarero-Grados, L and López-Del-Hoyo, Y and García-Campayo, J and Montero-Marin, J}, title = {Effectiveness of an amygdala and insula retraining program combined with mindfulness training to improve the quality of life in patients with long COVID: a randomized controlled trial protocol.}, journal = {BMC complementary medicine and therapies}, volume = {23}, number = {1}, pages = {403}, pmid = {37946190}, issn = {2662-7671}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mindfulness/methods ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: There has been growing clinical awareness in recent years of the long-term physical and psychological consequences of the SARS-CoV-2 virus, known as Long COVID. The prevalence of Long COVID is approximately 10% of those infected by the virus. Long COVID is associated with physical and neuropsychological symptoms, including those related to mental health, psychological wellbeing, and cognition. However, research on psychological interventions is still in its early stages, in which means that available results are still limited. The main objective of this study is to evaluate the effects of a program based on amygdala and insula retraining (AIR) combined with mindfulness training (AIR + Mindfulness) on the improvement of quality of life, psychological well-being, and cognition in patients with Long COVID.

METHODS: This study protocol presents a single-blind randomized controlled trial (RCT) that encompasses baseline, post-treatment, and six-month follow-up assessment time points. A total of 100 patients diagnosed with Long COVID by the Spanish National Health Service will be randomly assigned to either AIR + Mindfulness (n = 50) or relaxation intervention (n = 50), the latter as a control group. The primary outcome will be quality of life assessed using the Short Form-36 Health Survey (SF-36). Additional outcomes such as fatigue, pain, anxiety, memory, and sleep quality will also be evaluated. Mixed effects regression models will be used to estimate the effectiveness of the program, and effect size calculations will be made.

DISCUSSION: Long COVID syndrome is a clinical condition characterized by the persistence of symptoms for at least 12 weeks after the onset of COVID-19 that significantly affects people's quality of life. This will be the first RCT conducted in Spain to apply a psychotherapy program for the management of symptoms derived from Long COVID. Positive results from this RCT may have a significant impact on the clinical context by confirming the beneficial effect of the intervention program being evaluated on improving the symptoms of Long COVID syndrome and aiding the development of better action strategies for these patients.

TRIAL REGISTRATION: Clinical Trials.gov NCT05956405. Registered on July 20, 2023.}, } @article {pmid37944672, year = {2023}, author = {Hirschtick, JL and Xie, Y and Slocum, E and Hirschtick, RE and Power, LE and Elliott, MR and Orellana, RC and Fleischer, NL}, title = {A statewide population-based approach to examining Long COVID symptom prevalence and predictors in Michigan.}, journal = {Preventive medicine}, volume = {177}, number = {}, pages = {107752}, doi = {10.1016/j.ypmed.2023.107752}, pmid = {37944672}, issn = {1096-0260}, mesh = {Adult ; Middle Aged ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Michigan/epidemiology ; Prevalence ; }, abstract = {OBJECTIVE: The current broad definition of Long COVID, and an overreliance on clinical and convenience samples, is leading to a wide array of Long COVID estimates with limited generalizability. Our objective was to examine Long COVID symptoms using a statewide population-based probability sample.

METHODS: Among 8000 sampled adults with polymerase-chain-reaction-confirmed SARS-CoV-2 between June 2020 and July 2021 in the Michigan Disease Surveillance System, 2533 completed our survey (response rate 32.2%). Using modified Poisson regression, we examined sociodemographic, behavioral, and clinical predictors of eight Long COVID symptom clusters, defined as at least one applicable symptom lasting 90 or more days post COVID-19 onset.

RESULTS: Neuropsychiatric Long COVID symptoms, including brain fog, were most prevalent (23.7%), followed by systemic symptoms (17.1%), including fatigue, musculoskeletal (11.4%), pulmonary (10.4%), dermatologic (6.7%), cardiovascular (6.1%), gastrointestinal (5.4%), and ear, nose, and throat symptoms (5.3%). In adjusted analyses, female sex, a pre-existing psychological condition, and intensive care unit admission were strong predictors of most Long COVID symptom clusters. Older age was not associated with a higher prevalence of all symptoms - cardiovascular and dermatologic symptoms were most prevalent among middle-aged adults and age was not associated with neuropsychiatric or gastrointestinal symptoms. Additionally, there were fewer associations between pre-existing conditions and cardiovascular, neuropsychiatric, and dermatologic symptoms compared to other symptom clusters.

CONCLUSIONS: While many predictors of Long COVID symptom clusters were similar, the relationship with age and pre-existing conditions varied across clusters. Cardiovascular, neuropsychiatric, and dermatologic symptoms require further study as potentially distinct from other Long COVID symptoms.}, } @article {pmid37944296, year = {2024}, author = {Scheppke, KA and Pepe, PE and Jui, J and Crowe, RP and Scheppke, EK and Klimas, NG and Marty, AM}, title = {Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research.}, journal = {The American journal of emergency medicine}, volume = {75}, number = {}, pages = {122-127}, doi = {10.1016/j.ajem.2023.09.051}, pmid = {37944296}, issn = {1532-8171}, mesh = {Male ; Middle Aged ; Humans ; Female ; *Antibodies, Monoclonal/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: Long COVID has afflicted tens of millions globally leaving many previously-healthy persons severely and indefinitely debilitated. The objective here was to report cases of complete, rapid remission of severe forms of long COVID following certain monoclonal antibody (MCA) infusions and review the corresponding pathophysiological implications.

DESIGN: Case histories of the first three index events (among others) are presented. Unaware of others with similar remissions, each subject independently completed personal narratives and standardized surveys regarding demographics/occupation, past history, and the presence and respective severity grading of 33 signs/symptoms associated with long COVID, comparing the presence/severity of those symptoms during the pre-COVID, long-COVID, post-vaccination, and post-MCA phases.

SETTING: Patient interviews, e-mails and telephone conversations.

SUBJECTS: Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment.

INTERVENTIONS: The casirivimab/imdevimab cocktail.

MEASUREMENTS AND MAIN RESULTS: Irrespective of sex, age, medical history, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date over two years later.

CONCLUSIONS: These index cases provide compelling clinical signals that MCA infusions may be capable of treating long COVID in certain cases, including those with severe debilitation. While the complete and sustained remissions observed here may only apply to long COVID resulting from pre-Delta variants and the specific MCA infused, the striking rapid and complete remissions observed in these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions and long COVID from other variants.}, } @article {pmid37943302, year = {2023}, author = {Bhattacharjee, N and Sarkar, P and Sarkar, T}, title = {Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems.}, journal = {Physiology international}, volume = {110}, number = {4}, pages = {291-310}, doi = {10.1556/2060.2023.00256}, pmid = {37943302}, issn = {2498-602X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Acute Disease ; Pandemics ; SARS-CoV-2 ; }, abstract = {Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or "long COVID." The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others. Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation. To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.}, } @article {pmid37942323, year = {2023}, author = {Müller, L and Di Benedetto, S}, title = {From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1298004}, pmid = {37942323}, issn = {1664-3224}, mesh = {Humans ; Aged ; *Immunosenescence ; Autoimmunity ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Aging ; *Autoimmune Diseases ; Inflammation ; }, abstract = {The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function. Subsequent scrutiny of chronic inflammation, or "inflammaging," highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections. In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.}, } @article {pmid37942031, year = {2023}, author = {Gamrekeli, A and Ramirez-Fragoso, F and Ghamarnejad, O and Kardassis, D and Stöckle, F and Custodis, F and Stavrou, GA}, title = {Surgical therapy for major lung parenchymal damage from late coronavirus disease complication: case report and literature review.}, journal = {AME case reports}, volume = {7}, number = {}, pages = {33}, pmid = {37942031}, issn = {2523-1995}, abstract = {BACKGROUND: Coronavirus disease [severe acute respiratory syndrome coronavirus disease 19 (SARS COVID-19)] has emerged as one of the most challenging diseases of recent decades. After the pandemic outbreak, our knowledge of the virus has expanded and developed, but we face a new wave of atypical complications that require special attention. In addition to the acute complications of COVID-19 infection, late complications of the disease are taking an increasingly important part in the management of affected patients, which are grouped under the collective term "Long COVID". In this work, we present our therapy strategy in three cases of pulmonary cavity as a late complication after COVID-19, as well as perform a literature review of published articles in this matter.

CASE DESCRIPTION: This study includes 3 cases of pulmonary cavities as a late COVID complication. Among them only one patient was vaccinated. The mean duration between the occurrence of Long COVID and SARS COVID-19 disease was 4 weeks in our patients. All patients underwent adequate medical therapy after Long COVID. However, due to the disease progression and significant elevated infections parameters, all patients underwent surgical therapy. One patient underwent uniportal video-assisted thoracoscopic surgery (VATS) lobectomy and decortication of the empyema, whereas we performed thoracotomy for other patients. All patients treated successfully and discharged shortly after the operation. Our literature review provides a total of 12 publications with only 50 patients. No patients received vaccination. The mean interval time between acute infection and the appearance of pulmonary cavities was about 4 weeks. The results showed that most patients were treated with conservative therapies. Only two patients were treated using invasive therapies. Both patients were successfully treated and recovered from the procedures.

CONCLUSIONS: This group of late complications COVID patients requires individualized treatment strategy. In the case of an underlying pulmonary cavities, depending on the findings, despite increased perioperative risks, very good results can be achieved by presentation to a specialized and experienced thoracic surgery center.}, } @article {pmid37940843, year = {2023}, author = {Thi Khanh, HN and Cornelissen, L and Castanares-Zapatero, D and De Pauw, R and Van Cauteren, D and Demarest, S and Drieskens, S and Devleesschauwer, B and De Ridder, K and Charafeddine, R and Smith, P}, title = {Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {774}, pmid = {37940843}, issn = {1471-2334}, support = {internal funding//Sciensano/ ; }, mesh = {Adult ; Humans ; Longitudinal Studies ; *SARS-CoV-2/genetics ; *COVID-19/epidemiology ; Belgium/epidemiology ; Anosmia/epidemiology/etiology ; Dysgeusia ; Cohort Studies ; }, abstract = {BACKGROUND: While many studies on the determinants of post-COVID-19 conditions (PCC) have been conducted, little is known about the relationship between SARS-CoV-2 variants and PCC. This study aimed to assess the association between different SARS-CoV-2 variants and the probability of having PCC three months after the infection.

METHODS: This study was a longitudinal cohort study conducted between April 2021 and September 2022 in Belgium. In total, 8,238 adults with a confirmed SARS-CoV-2 infection were followed up between the time of their infection and three months later. The primary outcomes were the PCC status three months post infection and seven PCC symptoms categories (neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, anosmia and/or dysgeusia, and other manifestations). The main exposure variable was the type of SARS-CoV-2 variants (i.e. Alpha, Delta, and Omicron), extracted from national surveillance data. The association between the different SARS-CoV-2 variants and PCC as well as PCC symptoms categories was assessed using multivariable logistic regression.

RESULTS: The proportion of PCC among participants infected during the Alpha, Delta, and Omicron-dominant periods was significantly different and respectively 50%, 50%, and 37%. Participants infected during the Alpha- and Delta-dominant periods had a significantly higher odds of having PCC than those infected during the Omicron-dominant period (OR = 1.61, 95% confidence interval [CI] = 1.33-1.96 and OR = 1.73, 95%CI = 1.54-1.93, respectively). Participants infected during the Alpha and Delta-dominant periods were more likely to report neurocognitive, respiratory, and anosmia/dysgeusia symptoms of PCC.

CONCLUSIONS: People infected during the Alpha- and Delta-dominant periods had a higher probability of having PCC three months after infection than those infected during the Omicron-dominant period. The lower probability of PCC with the Omicron variant must also be interpreted in absolute figures. Indeed, the number of infections with the Omicron variant being higher than with the Alpha and Delta variants, it is possible that the overall prevalence of PCC in the population increases, even if the probability of having a PCC decreases.}, } @article {pmid37939376, year = {2023}, author = {Bamberger, C and Pankow, S and Martínez-Bartolomé, S and Diedrich, JK and Park, RSK and Yates, JR}, title = {Analysis of the Tropism of SARS-CoV-2 Based on the Host Interactome of the Spike Protein.}, journal = {Journal of proteome research}, volume = {22}, number = {12}, pages = {3742-3753}, doi = {10.1021/acs.jproteome.3c00387}, pmid = {37939376}, issn = {1535-3907}, mesh = {Humans ; *SARS-CoV-2/metabolism ; *COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Laminin ; Protein Binding ; Viral Proteins/metabolism ; Tropism ; }, abstract = {The β-coronavirus SARS-CoV-2 causes severe acute respiratory syndrome (COVID-19) in humans. It enters and infects epithelial airway cells upon binding of the receptor binding domain (RBD) of the virus entry protein spike to the host receptor protein Angiotensin Converting Enzyme 2 (ACE2). Here, we used coimmunoprecipitation coupled with bottom-up mass spectrometry to identify host proteins that engaged with the spike protein in human bronchial epithelial cells (16HBEo[-]). We found that the spike protein bound to extracellular laminin and thrombospondin and endoplasmatic reticulum (ER)-resident DJB11 and FBX2 proteins. The ER-resident proteins UGGT1, CALX, HSP7A, and GRP78/BiP bound preferentially to the original Wuhan D614 over the mutated G614 spike protein in the more rapidly spreading Alpha SARS-CoV-2 strain. The increase in protein binding to the D614 spike might be explained by higher accessibility of cryptic sites in "RDB open" and "S2 only" D614 spike protein conformations and may enable SARS-CoV-2 to infect additional, ACE2-negative cell types. Moreover, a novel proteome-based cell type set enrichment analysis (pCtSEA) found that host factors like laminin might render additional cell types such as macrophages and epithelial cells in the nephron permissive to SARS-CoV-2 infection.}, } @article {pmid37939338, year = {2023}, author = {Berger, M}, title = {COVID-19 Experience Reflects the Importance of Understanding the Impacts of Public Health Policies and Long COVID on Pediatric Populations.}, journal = {American journal of public health}, volume = {113}, number = {12}, pages = {1356-1357}, pmid = {37939338}, issn = {1541-0048}, mesh = {Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Health Policy ; Public Health ; }, } @article {pmid37938303, year = {2023}, author = {Kokkinakis, I and Saubade, M and Tzartzas, K and De Vallière, S and Duquenne, C and Allali, G and Regamey, F and Favrat, B}, title = {[Practical management of post-COVID-19 condition. Update and illustration by clinical situations].}, journal = {Revue medicale suisse}, volume = {19}, number = {849}, pages = {2094-2102}, doi = {10.53738/REVMED.2023.19.849.2094}, pmid = {37938303}, issn = {1660-9379}, mesh = {Humans ; *COVID-19 ; Ethnicity ; Interdisciplinary Studies ; Knowledge ; *Medicine ; }, abstract = {Persistent manifestations of COVID-19, known as «long COVID» or post-COVID-19 condition (RA02, CIM-11), affect many infected individuals, with a 24-month prevalence depending on the studies context (18 % in a recent Swiss study). The diversity of clinical presentation, the sometimes complex diagnostic methods, and the multidisciplinary management highlight the importance of a holistic approach, with practical advice for assessing work capacity in the outpatient setting. This article offers an update and synthesis of current knowledge concerning post-COVID-19 condition with practical recommendations for primary care medicine, illustrated by real clinical situations.}, } @article {pmid37936547, year = {2023}, author = {Wolff, D and Drewitz, KP and Ulrich, A and Siegels, D and Deckert, S and Sprenger, AA and Kuper, PR and Schmitt, J and Munblit, D and Apfelbacher, C}, title = {Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {53}, number = {11}, pages = {1162-1176}, doi = {10.1111/cea.14391}, pmid = {37936547}, issn = {1365-2222}, support = {//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Prospective Studies ; *Rhinitis ; *Asthma/epidemiology/etiology ; Risk Factors ; }, abstract = {OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC.

DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets.

DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched.

ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12 months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles.

RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence.

CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.}, } @article {pmid37936330, year = {2024}, author = {McIntyre, RS and Phan, L and Kwan, ATH and Mansur, RB and Rosenblat, JD and Guo, Z and Le, GH and Lui, LMW and Teopiz, KM and Ceban, F and Lee, Y and Bailey, J and Ramachandra, R and Di Vincenzo, J and Badulescu, S and Gill, H and Drzadzewski, P and Subramaniapillai, M}, title = {Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial.}, journal = {Brain : a journal of neurology}, volume = {147}, number = {3}, pages = {849-857}, doi = {10.1093/brain/awad377}, pmid = {37936330}, issn = {1460-2156}, support = {//H. Lundbeck A/S/ ; }, mesh = {Adult ; Humans ; *COVID-19 ; Vortioxetine/therapeutic use ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; C-Reactive Protein ; }, abstract = {Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [P = 0.361, 95% confidence interval (CI) (-0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [P < 0.001, 95% CI (-4.378, -2.323)] and HRQoL [P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (-2.847, -0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted.}, } @article {pmid37935992, year = {2023}, author = {Bird, L}, title = {Low serotonin linked to long COVID.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {12}, pages = {784}, pmid = {37935992}, issn = {1474-1741}, mesh = {Humans ; *Serotonin ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37932487, year = {2023}, author = {Wu, Y and Angelov, B and Deng, Y and Fujino, T and Hossain, MS and Drechsler, M and Angelova, A}, title = {Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies.}, journal = {Communications chemistry}, volume = {6}, number = {1}, pages = {241}, pmid = {37932487}, issn = {2399-3669}, support = {CZ.02.1.01/0.0/0.0/15_003/0000447 (ELIBIO)//EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)/ ; }, abstract = {Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson's disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration.}, } @article {pmid37931841, year = {2024}, author = {Borczuk, AC}, title = {Pathogenesis of Pulmonary Long COVID-19.}, journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc}, volume = {37}, number = {2}, pages = {100378}, doi = {10.1016/j.modpat.2023.100378}, pmid = {37931841}, issn = {1530-0285}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Lung ; Complement Activation ; }, abstract = {COVID-19 is characterized by an acute respiratory illness that, in some patients, progresses to respiratory failure, largely demonstrating a pattern of acute respiratory distress syndrome. Excluding fatal cases, the outcome of this severe illness ranges from complete resolution to persistent respiratory dysfunction. This subacute-to-chronic respiratory illness has different manifestations and is collectively termed as "long COVID." The pathogenesis of organ dysfunction in acute injury stems from exaggerated innate immune response, complement activation, and monocyte influx, with a shift toward an organ injury state with abnormalities in cellular maturation. Although the increased rate of thrombosis observed in acute COVID-19 does not appear to persist, interestingly, ongoing symptomatic COVID-19 and post-COVID pathogeneses appear to reflect the persistence of immune and cellular disturbances triggered by the acute and subacute periods.}, } @article {pmid37930308, year = {2024}, author = {Asamoah-Boaheng, M and Grunau, B and Karim, ME and Kirkham, TL and Demers, PA and MacDonald, C and Goldfarb, DM}, title = {The Association of Post-COVID-19-Related Symptoms and Preceding Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Fully Vaccinated Paramedics in Canada.}, journal = {The Journal of infectious diseases}, volume = {229}, number = {4}, pages = {1019-1025}, doi = {10.1093/infdis/jiad475}, pmid = {37930308}, issn = {1537-6613}, support = {//Government of Canada/ ; //COVID-19 Immunity Task Force/ ; //Michael Smith Health Research British Columbia/ ; //Centre for Health Evaluation and Outcome Sciences Research Trainee award/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Paramedics ; SARS-CoV-2 ; Canada/epidemiology ; }, abstract = {This study investigated the association between previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of symptoms associated with post-COVID conditions among fully vaccinated paramedics in Canada. We included vaccinated paramedics who provided blood sample and questionnaire data on the same date during the study period. We examined the presence of symptoms associated with post-COVID conditions and depression severity against prior SARS-CoV-2 infection categories. Compared to the "no previous SARS-CoV-2 infection" group, there was no detected association between known prior SARS-CoV-2 infection (odds ratio [OR], 1.42 [95% confidence interval {CI}, 0.96-2.09]), nor unknown prior SARS-CoV-2 infection (OR, 0.54 [95% CI, 0.29-1.00]), and the presence of symptoms associated with post-COVID conditions.}, } @article {pmid37929759, year = {2024}, author = {Yu, L and McCracken, LM}, title = {COVID-19 and mental health in the UK: Depression, anxiety and insomnia and their associations with persistent physical symptoms and risk and vulnerability factors.}, journal = {The British journal of clinical psychology}, volume = {63}, number = {1}, pages = {92-104}, doi = {10.1111/bjc.12446}, pmid = {37929759}, issn = {0144-6657}, mesh = {Adult ; Humans ; Mental Health ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; *Sleep Initiation and Maintenance Disorders/epidemiology ; *COVID-19/epidemiology ; Anxiety/epidemiology ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: Mental health problems and persistent COVID-19 symptoms were prevalent in the context of COVID-19. However, despite the long-observed association between physical symptoms and mental health problems, such association has not been adequately examined in the context of COVID-19. Our understanding of wider patterns of risk and vulnerability factors for mental health also remains limited. This study investigated the associations between general mental health, and persistent physical symptoms, and additional risk and vulnerability factors in the context of COVID-19.

METHODS: Two hundred fourteen adults, living in the UK, recruited via social media, completed the online survey and were included in the analyses. Correlation and regression analyses were conducted to examine the associations of persistent physical symptoms and risk and vulnerability factors with measures of general mental health including depressive symptoms, anxiety and insomnia.

RESULTS: 78.5% of the participants reported between 1 and 26 persistent symptoms, and about 28%-92% of them associated these symptoms with COVID-19 infection. Persistent physical symptoms were uniquely associated with all measures of mental health, β = .19-.32. Mental health history and worries were the most prominent risk factors, |β| = .12-.43.

CONCLUSIONS: People who experience more persistent physical symptoms post-COVID-19 have poorer mental health. It may be important to consider and discuss the recovery from COVID-19 beyond a negative COVID-19 test. Multidisciplinary interventions that address the complex impact of COVID-19 for people with long COVID are needed.}, } @article {pmid37927339, year = {2023}, author = {Matveeva, N and Kiselev, I and Baulina, N and Semina, E and Kakotkin, V and Agapov, M and Kulakova, O and Favorova, O}, title = {Shared genetic architecture of COVID-19 and Alzheimer's disease.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1287322}, pmid = {37927339}, issn = {1663-4365}, abstract = {The severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the сoronavirus disease 2019 (COVID-19) have become a global health threat. At the height of the pandemic, major efforts were focused on reducing COVID-19-associated morbidity and mortality. Now is the time to study the long-term effects of the pandemic, particularly cognitive impairment associated with long COVID. In recent years much attention has been paid to the possible relationship between COVID-19 and Alzheimer's disease, which is considered a main cause of age-related cognitive impairment. Genetic predisposition was shown for both COVID-19 and Alzheimer's disease. However, the analysis of the similarity of the genetic architecture of these diseases is usually limited to indicating a positive genetic correlation between them. In this review, we have described intrinsic linkages between COVID-19 and Alzheimer's disease, pointed out shared susceptibility genes that were previously identified in genome-wide association studies of both COVID-19 and Alzheimer's disease, and highlighted a panel of SNPs that includes candidate genetic risk markers of the long COVID-associated cognitive impairment.}, } @article {pmid37926103, year = {2023}, author = {Gorst, SL and Seylanova, N and Dodd, SR and Harman, NL and O'Hara, M and Terwee, CB and Williamson, PR and Needham, DM and Munblit, D and Nicholson, TR and , }, title = {Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {12}, pages = {1101-1114}, doi = {10.1016/S2213-2600(23)00370-3}, pmid = {37926103}, issn = {2213-2619}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Adult ; Delphi Technique ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Research Design ; Outcome Assessment, Health Care ; Treatment Outcome ; }, abstract = {Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes. We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated. The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes. The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.}, } @article {pmid37923365, year = {2024}, author = {Mariette, X}, title = {Long COVID: a new word for naming fibromyalgia?.}, journal = {Annals of the rheumatic diseases}, volume = {83}, number = {1}, pages = {12-14}, doi = {10.1136/ard-2023-224848}, pmid = {37923365}, issn = {1468-2060}, mesh = {Humans ; *Fibromyalgia/psychology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Communicable Disease Control ; Psychophysiologic Disorders/diagnosis/epidemiology/psychology ; }, abstract = {Long COVID is the name given to a syndrome comprising a wide variety of symptoms persisting more than 3 months after acute benign COVID-19, with a prevalence ranging from 10 to 80%. Symptoms are very close to fibromyalgia. Several studies showed that long COVID prevalence was much higher after the first wave of the pandemics and was associated to the fact of thinking having had COVID rather than having had really COVID. Thus, it was the stress of the first wave with the lockdown and not the consequences of the infection that probably induced this high frequency of long COVID. Numbers of studies tried to find objective biological abnormalities for explaining long COVID but none of them could be replicated and convincing. The concept of long COVID seems to be a repetition of history of medicine, in which the doctors and the society gave different names to fibromyalgia with the objective of trying to highlight the fact that fibromyalgia could be a somatic disease with a well understood pathophysiology and to avoid to focus on the psychosomatic aspects of the disease. In conclusion, "to name is to soothe" as said by Roland Barthes. However, "Naming things wrongly adds to the world's unhappiness" was saying Albert Camus. Thus, the term of long COVID, which suggests viral persistence of impaired immune response to the virus, is unappropriated and should be replaced by fibromyalgia-like post-COVID syndrome. Research on the psychosomatic and somatic mechanisms involved in these fibromyalgia-like post-viral syndromes must be encouraged.}, } @article {pmid37922783, year = {2023}, author = {Chen, SJ and Morin, CM and Ivers, H and Wing, YK and Partinen, M and Merikanto, I and Holzinger, B and Espie, CA and De Gennaro, L and Dauvilliers, Y and Chung, F and Yordanova, J and Vidović, D and Reis, C and Plazzi, G and Penzel, T and Nadorff, MR and Matsui, K and Mota-Rolim, S and Leger, D and Landtblom, AM and Korman, M and Inoue, Y and Hrubos-Strøm, H and Chan, NY and Bjelajac, AK and Benedict, C and Bjorvatn, B}, title = {The association of insomnia with long COVID: An international collaborative study (ICOSS-II).}, journal = {Sleep medicine}, volume = {112}, number = {}, pages = {216-222}, doi = {10.1016/j.sleep.2023.09.034}, pmid = {37922783}, issn = {1878-5506}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *COVID-19/complications/epidemiology ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; Depression/diagnosis ; Anxiety/epidemiology/diagnosis ; }, abstract = {OBJECTIVE: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.

METHODS: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.

RESULTS: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).

CONCLUSIONS: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.}, } @article {pmid37924708, year = {2023}, author = {Gu, X and Wang, S and Zhang, W and Li, C and Guo, L and Wang, Z and Li, H and Zhang, H and Zhou, Y and Liang, W and Li, H and Liu, Y and Wang, Y and Huang, L and Dong, T and Zhang, D and Wong, CCL and Cao, B}, title = {Probing long COVID through a proteomic lens: a comprehensive two-year longitudinal cohort study of hospitalised survivors.}, journal = {EBioMedicine}, volume = {98}, number = {}, pages = {104851}, pmid = {37924708}, issn = {2352-3964}, mesh = {Humans ; Male ; Female ; Cohort Studies ; Longitudinal Studies ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Cardiomyopathy, Dilated ; Proteomics ; Biomarkers ; Survivors ; Cholesterol ; }, abstract = {BACKGROUND: As a debilitating condition that can impact a whole spectrum of people and involve multi-organ systems, long COVID has aroused the most attention than ever. However, mechanisms of long COVID are not clearly understood, and underlying biomarkers that can affect the long-term consequences of COVID-19 are paramount to be identified.

METHODS: Participants for the current study were from a cohort study of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. We profiled the proteomic of plasma samples from hospitalised COVID-19 survivors at 6-month, 1-year, and 2-year after symptom onset and age and sex matched healthy controls. Fold-change of >2 or <0.5, and false-discovery rate adjusted P value of 0.05 were used to filter differentially expressed proteins (DEPs). In-genuity pathway analysis was performed to explore the down-stream effects in the dataset of significantly up- or down-regulated proteins. Proteins were integrated with long-term consequences of COVID-19 survivors to explore potential biomarkers of long COVID.

FINDINGS: The proteomic of 709 plasma samples from 181 COVID-19 survivors and 181 matched healthy controls was profiled. In both COVID-19 and control group, 114 (63%) were male. The results indicated four major recovery modes of biological processes. Pathways related to cell-matrix interactions and cytoskeletal remodeling and hypertrophic cardiomyopathy and dilated cardiomyopathy pathways recovered relatively earlier which was before 1-year after infection. Majority of immune response pathways, complement and coagulation cascade, and cholesterol metabolism returned to similar status of matched healthy controls later but before 2-year after infection. Fc receptor signaling pathway still did not return to status similar to healthy controls at 2-year follow-up. Pathways related to neuron generation and differentiation showed persistent suppression across 2-year after infection. Among 98 DEPs from the above pathways, evidence was found for association of 11 proteins with lung function recovery, with the associations consistent at two consecutive or all three follow-ups. These proteins were mainly enriched in complement and coagulation (COMP, PLG, SERPINE1, SRGN, COL1A1, FLNA, and APOE) and hypertrophic/dilated cardiomyopathy (TPM2, TPM1, and AGT) pathways. Two DEPs (APOA4 and LRP1) involved in both neuron and cholesterol pathways showed associations with smell disorder.

INTERPRETATION: The study findings provided molecular insights into potential mechanism of long COVID, and put forward biomarkers for more precise intervention to reduce burden of long COVID.

FUNDING: National Natural Science Foundation of China; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences; Clinical Research Operating Fund of Central High Level Hospitals; the Talent Program of the Chinese Academy of Medical Science; Training Program of the Big Science Strategy Plan; Ministry of Science and Technology of the People's Republic of China; New Cornerstone Science Foundation; Peking Union Medical College Education Foundation; Research Funds from Health@InnoHK Program.}, } @article {pmid37924472, year = {2024}, author = {Pink, I and Hennigs, JK and Ruhl, L and Sauer, A and Boblitz, L and Huwe, M and Fuge, J and Falk, CS and Pietschmann, T and de Zwaan, M and Prasse, A and Kluge, S and Klose, H and Hoeper, MM and Welte, T}, title = {Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19.}, journal = {Infection}, volume = {52}, number = {2}, pages = {513-524}, pmid = {37924472}, issn = {1439-0973}, support = {COFONI-2FF4//COVID-19 -Research Network of the State of Lower Saxony (COFONI), Ministry of Science and Culture of Lower Saxony, Germany/ ; 14-76103-184 CORONA-13/20//COVID-19 -Research Network of the State of Lower Saxony (COFONI), Ministry of Science and Culture of Lower Saxony, Germany/ ; project 07_913//Deutsches Zentrum für Infektionsforschung/ ; }, mesh = {Humans ; *T-Lymphocytes ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Prospective Studies ; Phenotype ; Disease Progression ; Fatigue/etiology ; }, abstract = {PURPOSE: Post-acute sequelae of COVID-19 (PASC) affect approximately 10% of convalescent patients. The spectrum of symptoms is broad and heterogeneous with fatigue being the most often reported sequela. Easily accessible blood biomarkers to determine PASC severity are lacking. Thus, our study aimed to correlate immune phenotypes with PASC across the severity spectrum of COVID-19.

METHODS: A total of 176 originally immunonaïve, convalescent COVID-19 patients from a prospective cohort during the first pandemic phase were stratified by initial disease severity and underwent clinical, psychosocial, and immune phenotyping around 10 weeks after first COVID-19 symptoms. COVID-19-associated fatigue dynamics were assessed and related to clinical and immune phenotypes.

RESULTS: Fatigue and severe fatigue were commonly reported irrespective of initial COVID-19 severity or organ-specific PASC. A clinically relevant increase in fatigue severity after COVID-19 was detected in all groups. Neutralizing antibody titers were higher in patients with severe acute disease, but no association was found between antibody titers and PASC. While absolute peripheral blood immune cell counts in originally immunonaïve PASC patients did not differ from unexposed controls, peripheral CD3[+]CD4[+] T cell counts were independently correlated with fatigue severity across all strata in multivariable analysis.

CONCLUSIONS: Patients were at similar risk of self-reported PASC irrespective of initial disease severity. The independent correlation between fatigue severity and blood T cell phenotypes indicates a possible role of CD4[+] T cells in the pathogenesis of post-COVID-19 fatigue, which might serve as a blood biomarker.}, } @article {pmid37924387, year = {2023}, author = {Pan, JQ and Tian, ZM and Xue, LB}, title = {Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice.}, journal = {Current medical science}, volume = {43}, number = {6}, pages = {1061-1065}, pmid = {37924387}, issn = {2523-899X}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; Oxygen ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Epstein-Barr Virus Infections ; *COVID-19/therapy ; Herpesvirus 4, Human ; }, abstract = {Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus reactivation. Hyperbaric oxygen therapy (HBOT) is a therapeutic method in which a person inhales 100% oxygen under pressure greater than that of the atmosphere. HBOT has some therapeutic effects, including improvement of microcirculation, inhibition of cytokine release leading to a reduction in inflammatory responses, inhibition of autoimmune responses, and promotion of neurological repair. Several clinical trials have been carried out using HBOT to treat long COVID. The results suggest that HBOT helps to improve symptom severity, reduce symptom duration, and enhance patients' quality of life. It is believed that HBOT is an effective option for patients with long COVID, which is worth actively promoting.}, } @article {pmid37922371, year = {2023}, author = {Sigler, R and Covarrubias, K and Chen, B and Rubarth, RB and Torosian, K and Sanchez, CR and Bharti, A and DeGruttola, V and Aslam, S}, title = {Post-acute sequelae of COVID-19 in solid organ transplant recipients.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {25}, number = {6}, pages = {e14167}, pmid = {37922371}, issn = {1399-3062}, support = {T15 LM011271/LM/NLM NIH HHS/United States ; T15LM011271/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; COVID-19 Testing ; *COVID-19 Vaccines/administration & dosage ; Disease Progression ; *Organ Transplantation ; Post-Acute COVID-19 Syndrome/epidemiology ; Retrospective Studies ; *Transplant Recipients ; }, abstract = {BACKGROUND: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors.

METHODS: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis.

RESULTS: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective.

CONCLUSION: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.}, } @article {pmid37920733, year = {2023}, author = {Martínez-Borba, V and Martínez-García, L and Peris-Baquero, Ó and Osma, J and Del Corral-Beamonte, E}, title = {Unified Protocol for the transdiagnostic treatment of emotional disorders in people with post COVID-19 condition: study protocol for a multiple baseline n-of-1 trial.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1160692}, pmid = {37920733}, issn = {1664-1078}, abstract = {BACKGROUND: Post COVID-19 syndrome, defined as the persistence of COVID-19 symptoms beyond 3 months, is associated with a high emotional burden. Post COVID-19 patients frequently present comorbid anxiety, depressive and related disorders (emotional disorders, EDs) which have an important impact on their quality of life. Unfortunately, psychological interventions to manage these EDs are rarely provided to post COVID-19 patients. Also importantly, most psychological interventions do not address comorbidity, namely simultaneous EDs present in COVID-19 patients. This study will explore the clinical utility and acceptability of a protocol-based cognitive-behavioral therapy called the Unified Protocol for the transdiagnostic treatment of EDs in patients suffering post COVID-19 condition.

METHODS: A multiple baseline n-of-1 trial will be used, as it allows participants to be their own comparison control. Sample will be composed of 60 patients diagnosed with post COVID-19 conditions and comorbid EDs from three Spanish hospitals. After meeting the eligibility criteria, participants will answer the pre-assessment protocol and then they will be randomly assigned to three different baseline conditions (6, 8, or 10 days of assessments before the intervention). Participants and professionals will be unblinded to participants' allocation. Once the baseline assessment has been completed, participants will receive the online psychological individual intervention through video-calls. The Unified Protocol intervention will comprise 8 sessions of a 1 h duration each. After the intervention, participants will answer the post-assessment protocol. Additional follow-up assessments will be conducted at one, three, six, and twelve months after the intervention. Primary outcomes will be anxiety and depressive symptoms. Secondary outcomes include quality of life, emotion dysregulation, distress tolerance, and satisfaction with the programme. Data analyses will include between-group and within-group differences and visual analysis of patients' progress.

DISCUSSION: Results from this study will be disseminated in scientific journals. These findings may help to provide valuable information in the implementation of psychological interventions for patients suffering post COVID-19 conditions.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, identifier (NCT05581277).}, } @article {pmid37920139, year = {2023}, author = {Engelmann, P and Büchel, C and Frommhold, J and Klose, HFE and Lohse, AW and Maehder, K and Nestoriuc, Y and Scherer, M and Suling, A and Toussaint, A and Weigel, A and Zapf, A and Löwe, B}, title = {Psychological risk factors for Long COVID and their modification: study protocol of a three-arm, randomised controlled trial (SOMA.COV).}, journal = {BJPsych open}, volume = {9}, number = {6}, pages = {e207}, pmid = {37920139}, issn = {2056-4724}, support = {508447247//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Growing evidence suggests that in addition to pathophysiological, there are psychological risk factors involved in the development of Long COVID. Illness-related anxiety and dysfunctional symptom expectations seem to contribute to symptom persistence.

AIMS: With regard to the development of effective therapies, our primary aim is to investigate whether symptoms of Long COVID can be improved by a targeted modification of illness-related anxiety and dysfunctional symptom expectations. Second, we aim to identify additional psychosocial risk factors that contribute to the persistence of Long COVID, and compare them with risk factors for symptom persistence in other clinical conditions.

METHOD: We will conduct an observer-blinded, three-arm, randomised controlled trial. A total of 258 patients with Long COVID will be randomised into three groups of equal size: targeted expectation management in addition to treatment as usual (TAU), non-specific supportive treatment plus TAU, or TAU only. Both active intervention groups will comprise three individual online video consultation sessions and a booster session after 3 months. The primary outcome is baseline to post-interventional change in overall somatic symptom severity.

CONCLUSIONS: The study will shed light onto the action mechanisms of a targeted expectation management intervention for Long COVID, which, if proven effective, can be used stand-alone or in the context of broader therapeutic approaches. Further, the study will enable a better understanding of symptom persistence in Long COVID by identifying additional psychological risk factors.}, } @article {pmid37919765, year = {2023}, author = {Wyper, GMA and McDonald, SA and Haagsma, JA and Devleesschauwer, B and Charalampous, P and Maini, R and Smith, P and Pires, SM}, title = {A proposal for further developing fatigue-related post COVID-19 health states for burden of disease studies.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {81}, number = {1}, pages = {193}, pmid = {37919765}, issn = {0778-7367}, abstract = {Previous efforts to estimate the burden of fatigue-related symptoms due to long COVID have a very high threshold for inclusion of cases, relative to the proposed definition from the World Health Organization. In practice this means that milder cases, that may be occurring very frequently, are not included in estimates of the burden of long COVID which will result in underestimation. A more comprehensive approach to modelling the disease burden from long COVID, in relation to fatigue, can ensure that we do not only focus on what is easiest to measure; which risks losing focus of less severe health states that may be more difficult to measure but are occurring very frequently. Our proposed approach provides a means to better understand the scale of challenge from long COVID, for consideration when preventative and mitigative action is being planned.}, } @article {pmid37919074, year = {2023}, author = {Marschalek, R}, title = {SARS-CoV-2: The Virus, Its Biology and COVID-19 Disease-Counteracting Possibilities.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {10}, pages = {273}, doi = {10.31083/j.fbl2810273}, pmid = {37919074}, issn = {2768-6698}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Biology ; }, abstract = {Since the end of 2019, the SARS-CoV-2 virus started to spread in different countries, leading to a world-wide pandemia, with today's infection numbers of more than 690 million and with a case fatality rate of more than 6.9 million. In addition, about 65 million patients suffer from post/long-Covid syndromes after having infections with the SARS-CoV-2 virus or variants thereof. This review highlights the biology of the virus, summarizes our knowledge of some of the viral mechanisms that counteract our immune responses, and finally also discusses the different vaccines and their specific safety profiles. Also, the possibility to fight this virus with recently available drugs (Veklury, Lagevrio and Paxlovid) will be discussed. All these data clearly argue that SARS-CoV-2 variants still exhibit a dangerous potential-although with a lower case fatality rate-and that vaccination in combination with drug intake upon infection may help to lower the risk of developing chronic or temporary autoimmune diseases.}, } @article {pmid37918226, year = {2023}, author = {Stelson, EA and Dash, D and McCorkell, L and Wilson, C and Assaf, G and Re'em, Y and Wei, H}, title = {Return-to-work with long COVID: An Episodic Disability and Total Worker Health® analysis.}, journal = {Social science & medicine (1982)}, volume = {338}, number = {}, pages = {116336}, doi = {10.1016/j.socscimed.2023.116336}, pmid = {37918226}, issn = {1873-5347}, mesh = {Humans ; Return to Work ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Employment ; *Disabled Persons ; Workplace ; }, abstract = {A growing number of working individuals have developed long COVID (LC) after COVID-19 infection. Economic analyses indicate that workers' LC symptoms contribute to workforce shortages. However, factors that affect return-to-work from perspectives of people with LC remain largely underexplored. This qualitative study of people with LC conducted by researchers living with LC aimed to identify participants' return-to-work experiences using Total Worker Health® and Episodic Disability frameworks. 10% of participants who participated in a mixed-method global internet survey, had LC symptoms >3 months, and responded in English were randomly selected for thematic analysis using NVivo12. 15% of responses were independently double-coded to identify coding discrepancies. Participants (N = 510) were predominately white and had at least a baccalaureate degree. Four primary work-related themes emerged: 1) strong desire and need to return to work motivated by sense of purpose and financial precarity; 2) diverse and episodic LC symptoms intersect with organization of work and home life; 3) pervasiveness of LC disbelief and stigma at work and in medical settings; and 4) support of medical providers is key to successful return-to-work. Participants described how fluctuation of symptoms, exacerbated by work-related tasks, made returning to work challenging. Participants' ability to work was often predicated on job accommodations and support. Non-work factors were also essential, especially being able to receive an LC medical diagnosis (key to accessing leave and accommodations) and help at home to manage non-work activities. Many participants described barriers accessing these supports, illuminating stigma and disbelief in LC as a medical condition. Qualitative findings indicate needs for workplace accommodations tailored to fluctuating symptoms, continuously re-evaluated by workers and supervisors together. Reductions in medical barriers to access work accommodations is also critical since many medical providers remain unaware of LC, and workers may lack a positive COVID test result.}, } @article {pmid37917610, year = {2023}, author = {Blanchflower, DG and Bryson, A}, title = {Long COVID in the United States.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0292672}, pmid = {37917610}, issn = {1932-6203}, mesh = {Male ; Humans ; Female ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Income ; Educational Status ; White ; }, abstract = {Although yet to be clearly identified as a clinical condition, there is immense concern at the health and wellbeing consequences of long COVID. Using data collected from nearly half a million Americans in the period June 2022-December 2022 in the US Census Bureau's Household Pulse Survey (HPS), we find 14 percent reported suffering long COVID at some point, half of whom reported it at the time of the survey. Its incidence varies markedly across the United States-from 11 percent in Hawaii to 18 percent in West Virginia-and is higher for women than men, among Whites compared with Blacks and Asians, and declines with rising education and income. It is at its highest in midlife in the same way as negative affect. Ever having had long COVID is strongly associated with negative affect (anxiety, depression, worry and a lack of interest in things), with the correlation being strongest among those who currently report long COVID, especially if they report severe symptoms. In contrast, those who report having had short COVID report higher wellbeing than those who report never having had COVID. Long COVID is also strongly associated with physical mobility problems, and with problems dressing and bathing. It is also associated with mental problems as indicated by recall and understanding difficulties. Again, the associations are strongest among those who currently report long COVID, while those who said they had had short COVID have fewer physical and mental problems than those who report never having had COVID. Vaccination is associated with lower negative affect, including among those who reported having had long COVID.}, } @article {pmid37915705, year = {2023}, author = {Shariff, S and Uwishema, O and Mizero, J and Devi Thambi, V and Nazir, A and Mahmoud, A and Kaushik, I and Khayat, S and Yusif Maigoro, A and Awde, S and Al Maaz, Z and Alwan, I and Hijazi, M and Wellington, J and Soojin, L}, title = {Long-term cognitive dysfunction after the COVID-19 pandemic: a narrative review.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {11}, pages = {5504-5510}, pmid = {37915705}, issn = {2049-0801}, abstract = {INTRODUCTION: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has brought a conglomerate of novel chronic disabling conditions described as 'Long COVID/Post-COVID-19 Syndrome'. Recent evidence suggests that the multifaceted nature of this syndrome results in both pulmonary and extrapulmonary sequelae,chronic dyspnoea, persistent fatigue, and cognitive dysfunction being the most common, debilitating symptoms. Several mechanisms engender or exacerbate cognitive impairment, including central nervous system and extra-central nervous system causes, although the exact mechanism remains unclear. Both hospitalized and non-hospitalized patients may suffer varying degrees of cognitive impairment, ranging from fatigue and brain fog to prolonged deficits in memory and attention, detrimental to the quality-of-life years post-recovery. The aim of this review is to understand the underlying mechanisms, associations, and attempts for prevention with early intervention of long-term cognitive impairment post-COVID-19.

METHODOLOGY: A systematic search was conducted through multiple databases such as Medline, National Library of Medicine, Ovid, Scopus database to retrieve all the articles on the long-term sequalae of cognitive dysfunction after SARS-CoV-2 infection. The inclusion criteria included all articles pertinent to this specific topic and exclusion criteria subtracted studies pertaining to other aetiologies of cognitive dysfunction. This search was carefully screened for duplicates and the relevant information was extracted and analysed.

RESULTS/DISCUSSION: To date, the exact pathogenesis, and underlying mechanisms behind cognitive dysfunction in COVID-19, remain unclear, hindering the development of adequate management strategies. However, the proposed mechanisms suggested by various studies include direct damage to the blood-brain barrier, systemic inflammation, prolonged hypoxia, and extended intensive care admissions. However, no clear-cut guidelines for management are apparent.

CONCLUSION: This review of the COVID-19 pandemic has elucidated a new global challenge which is affecting individuals' quality of life by inducing long-term impaired cognitive function. The authors have found that comprehensive evaluations and interventions are crucial to address the cognitive sequelae in all COVID-19 patients, especially in patients with pre-existing cognitive impairment. Nevertheless, the authors recommend further research for the development of relevant, timely neurocognitive assessments and treatment plans.}, } @article {pmid37915075, year = {2023}, author = {Taylor, K and Pearson, M and Das, S and Sardell, J and Chocian, K and Gardner, S}, title = {Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {775}, pmid = {37915075}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/genetics ; SARS-CoV-2 ; Risk Factors ; }, abstract = {BACKGROUND: Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that present with similar symptoms.

METHODS: We used a combinatorial analysis approach to identify combinations of genetic variants significantly associated with the development of long COVID and to examine the biological mechanisms underpinning its various symptoms. We compared two subpopulations of long COVID patients from Sano Genetics' Long COVID GOLD study cohort, focusing on patients with severe or fatigue dominant phenotypes. We evaluated the genetic signatures previously identified in an ME/CFS population against this long COVID population to understand similarities with other fatigue disorders that may be triggered by a prior viral infection. Finally, we also compared the output of this long COVID analysis against known genetic associations in other chronic diseases, including a range of metabolic and neurological disorders, to understand the overlap of pathophysiological mechanisms.

RESULTS: Combinatorial analysis identified 73 genes that were highly associated with at least one of the long COVID populations included in this analysis. Of these, 9 genes have prior associations with acute COVID-19, and 14 were differentially expressed in a transcriptomic analysis of long COVID patients. A pathway enrichment analysis revealed that the biological pathways most significantly associated with the 73 long COVID genes were mainly aligned with neurological and cardiometabolic diseases. Expanded genotype analysis suggests that specific SNX9 genotypes are a significant contributor to the risk of or protection against severe long COVID infection, but that the gene-disease relationship is context dependent and mediated by interactions with KLF15 and RYR3. Comparison of the genes uniquely associated with the Severe and Fatigue Dominant long COVID patients revealed significant differences between the pathways enriched in each subgroup. The genes unique to Severe long COVID patients were associated with immune pathways such as myeloid differentiation and macrophage foam cells. Genes unique to the Fatigue Dominant subgroup were enriched in metabolic pathways such as MAPK/JNK signaling. We also identified overlap in the genes associated with Fatigue Dominant long COVID and ME/CFS, including several involved in circadian rhythm regulation and insulin regulation. Overall, 39 SNPs associated in this study with long COVID can be linked to 9 genes identified in a recent combinatorial analysis of ME/CFS patient from UK Biobank. Among the 73 genes associated with long COVID, 42 are potentially tractable for novel drug discovery approaches, with 13 of these already targeted by drugs in clinical development pipelines. From this analysis for example, we identified TLR4 antagonists as repurposing candidates with potential to protect against long term cognitive impairment pathology caused by SARS-CoV-2. We are currently evaluating the repurposing potential of these drug targets for use in treating long COVID and/or ME/CFS.

CONCLUSION: This study demonstrates the power of combinatorial analytics for stratifying heterogeneous populations in complex diseases that do not have simple monogenic etiologies. These results build upon the genetic findings from combinatorial analyses of severe acute COVID-19 patients and an ME/CFS population and we expect that access to additional independent, larger patient datasets will further improve the disease insights and validate potential treatment options in long COVID.}, } @article {pmid37914226, year = {2024}, author = {Faux-Nightingale, A and Saunders, B and Burton, C and Chew-Graham, CA and Somayajula, G and Twohig, H and Welsh, V}, title = {Experiences and care needs of children with long COVID: a qualitative study.}, journal = {BJGP open}, volume = {8}, number = {1}, pages = {}, pmid = {37914226}, issn = {2398-3795}, abstract = {BACKGROUND: Long COVID, the patient-preferred term, describes symptoms persisting after an acute episode of COVID-19 infection. Symptoms in children and young people (CYP) can affect daily routine, with broader impacts on education, health-related quality of life, and social activities, which may have long-term effects on health and wellbeing.

AIM: To explore the lived experiences and care needs of CYP with long COVID from the perspectives of CYP with long COVID, their parents, and professionals associated with the care of children and families living with the condition.

DESIGN & SETTING: CYP and their parent or carer were invited for interview following participation in a cohort study, which recruited the sample from a primary care setting.

METHOD: Interviews were carried out with four CYP with long COVID (all female, aged 10-17 years); three interviews included a parent. Two focus groups were conducted, which included seven professionals involved with care of CYP or long COVID, from a range of disciplines. Interviews and focus groups were transcribed verbatim, and data analysed thematically using constant comparison techniques.

RESULTS: The three main themes presented are as follows: living with long COVID; uncertainty surrounding long COVID; and seeking help for symptoms.

CONCLUSION: Long COVID can severely impact the lives of CYP and their families. CYP and their families need to be listened to by professionals and have any uncertainties acknowledged. It is imperative that agencies working with them understand the condition and its impact, and are able to offer support where needed.}, } @article {pmid37910132, year = {2023}, author = {Harris, E}, title = {Long COVID Linked With Viral Persistence, Serotonin Decline.}, journal = {JAMA}, volume = {330}, number = {19}, pages = {1827}, doi = {10.1001/jama.2023.21170}, pmid = {37910132}, issn = {1538-3598}, mesh = {Humans ; COVID-19/complications/virology ; *Post-Acute COVID-19 Syndrome/blood/etiology/virology ; *SARS-CoV-2/isolation & purification ; *Serotonin/analysis ; Viral Load ; }, } @article {pmid37908849, year = {2023}, author = {Chen, C and Parthasarathy, S and Leung, JM and Wu, MJ and Drake, KA and Ridaura, VK and Zisser, HC and Conrad, WA and Tapson, VF and Moy, JN and deFilippi, CR and Rosas, IO and Prabhakar, BS and Basit, M and Salvatore, M and Krishnan, JA and Kim, CC}, title = {Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1227883}, pmid = {37908849}, issn = {2296-858X}, support = {UL1 TR002384/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.

METHODS: We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.

RESULTS: We identified three phenotypic clusters associated with PASC that could be characterized as remittent, persistent, or incident based on the 3-month change in symptom number compared to study entry: remittent (median; min, max: -4; -17, 3), persistent (-2; -14, 7), or incident (4.5; -5, 17) (p = 0.041 remittent vs. persistent, p < 0.001 remittent vs. incident, p < 0.001 persistent vs. incident). Despite younger age and lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, 24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, 4.36)].

CONCLUSION: An incident disease phenotype characterized by symptoms that were absent during acute illness and the observed association with high dose steroids during acute illness have potential critical implications for preventing PASC.}, } @article {pmid37907497, year = {2023}, author = {Li, J and Zhou, Y and Ma, J and Zhang, Q and Shao, J and Liang, S and Yu, Y and Li, W and Wang, C}, title = {The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {416}, pmid = {37907497}, issn = {2059-3635}, support = {2021M692309, 2022T150451//China Postdoctoral Science Foundation/ ; 2020HXBH084, CGZH21009//Sichuan University (SCU)/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Outcome Assessment, Health Care ; }, abstract = {There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.}, } @article {pmid37907337, year = {2024}, author = {Al-Jabr, H and Windle, K and Clifton, A and Thompson, DR and Castle, DJ and Ski, CF}, title = {Patient experiences of the Long COVID-Optimal Health Programme: a qualitative interview study in community settings.}, journal = {BJGP open}, volume = {8}, number = {1}, pages = {}, pmid = {37907337}, issn = {2398-3795}, abstract = {BACKGROUND: Long COVID (LC) symptoms persist 12 weeks or more beyond the acute infection. To date, no standardised diagnostic or treatment pathways exist. However, a holistic approach has been recommended. This study explored participants' experiences of a Long COVID-Optimal Health Programme (LC-OHP); a psychoeducational self-efficacy programme.

AIM: To explore perceptions and experiences of people with LC regarding the LC-OHP and identify suggestions to further improve the programme.

DESIGN & SETTING: Qualitative study with patients with LC recruited through community settings.

METHOD: This study is part of a wider randomised controlled trial. Eligible participants were aged ≥18 years, have LC, and attended a minimum of five LC-OHP sessions plus a booster session. We interviewed those randomised to the intervention group. Interviews were conducted by an independent researcher and thematically analysed to identify common, emerging themes.

RESULTS: Eleven participants were interviewed, mostly women from a White British ethnic group (n = 10). Four main themes were identified, reflecting programme benefits and suggestions for improvement. The programme demonstrated potential for assisting patients in managing their LC, including physical health and mental wellbeing. Participants found the programme to be flexible and provided suggestions to adapting it for future users.

CONCLUSION: Findings support the acceptability of the LC-OHP to people living with LC. The programme has shown several benefits in supporting physical health and mental wellbeing. Suggestions made to further adapt the programme and improve its delivery will be considered for future trials.}, } @article {pmid37907217, year = {2023}, author = {Hayden, MC and Schuler, M and Limbach, M and Schwarzl, G and Stenzel, N and Nowak, D and Schultz, K}, title = {[Patient-Reported Outcomes (PROs) 3 and 6 Months After Pulmonary Rehabilitation Following COVID-19].}, journal = {Die Rehabilitation}, volume = {62}, number = {6}, pages = {349-358}, doi = {10.1055/a-2134-2142}, pmid = {37907217}, issn = {1439-1309}, mesh = {Humans ; Male ; Female ; *COVID-19 ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Germany/epidemiology ; Dyspnea/rehabilitation ; Pain ; Patient Reported Outcome Measures ; Fatigue ; }, abstract = {PURPOSE: If COVID-19 disease sequelae also (co-)affect the respiratory organs, national and international guidelines recommend pulmonary rehabilitation (PR). So far, however, no studies are available from Germany on the course after PR, nor on possible course differences between the two Long COVID subgroups "Ongoing symptomatic COVID-19" and "Post-COVID-19 syndrome" (PCS).

METHODS:   In a prospective observational study, patient-reported outcomes (PROs) regarding exertional dyspnea, quality of life, pain, fatigue, depression, and anxiety were assessed at the beginning of PR (T1), end of PR (T2), and after 3 (T3) and 6 months (T4). Statistical analyses were performed using latent difference models.

RESULTS:   There were 224 rehabilitation patients (MAge=54.4; SDAge=10.4; 42.0% female) included in the study. During PR, all PROs improved significantly. After PR, improvements either persisted with large pre-post effect sizes (exertional dyspnea, quality of life), decreased slightly to small pre-post effect sizes (depression, fatigue), or decreased to baseline levels (anxiety, pain). PCS patients had greater burdens in depression, fatigue, and pain at baseline, but did not differ in trajectories. Indicators of the severity of the preceding acute phase (oxygen therapy, ICU treatment, ventilation) were associated with higher burdens at T0 in depression, fatigue, and pain, but not with the courses during and after PR. In contrast, female patients showed higher burdens in both depression and fatigue at T1 and higher pre-post effects than male patients.

CONCLUSION:   The fact that improvements in PROs occurred in both subgroups only during PR, but not during the follow-up period suggests that the changes are not due to the natural healing process but at least partly due to PR. Moreover, the results suggest that both patient groups may benefit from PR. Persisting improvements in exertional dyspnea and quality of life and, to a reduced extent, in depression and fatigue until 6 months after PR, but not in pain and anxiety warrant study of additional multimodal interventions that may be needed to maintain these effects.}, } @article {pmid37907167, year = {2023}, author = {Agergaard, J and Gunst, JD and Schiøttz-Christensen, B and Østergaard, L and Wejse, C}, title = {Long-term prognosis at 1.5 years after infection with wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron variants.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {137}, number = {}, pages = {126-133}, doi = {10.1016/j.ijid.2023.10.022}, pmid = {37907167}, issn = {1878-3511}, mesh = {Humans ; *SARS-CoV-2/genetics ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Prognosis ; }, abstract = {OBJECTIVES: Knowledge is limited on how changing SARS-CoV-2 variants may translate into different characteristics and affect the prognosis of patients with long COVID, especially following Omicron variants. We compared long-term prognosis of patients in a Danish Post-COVID Clinic infected with wild-type strain, Alpha, Delta, or Omicron variants as well as the pre-Omicron compared to the Omicron period.

METHODS: At enrollment, a Post-COVID symptom Questionnaire (PCQ), and standard health scores, were registered and repeated four times until 1.5 years after infection. PCQ was the primary outcome to assess the severity of long COVID, and Delta PCQ to assess failure to improve.

RESULTS: A total of 806 patients were enrolled. Patients infected with Omicron and Delta variants presented with more severe long COVID (median PCQ 43 in Delta vs 38 in wild-type, P = 0.003) and health scores (EuroQol five-dimension five-level-index was 0.70 in Omicron vs 0.76 in wild-type, P = 0.009 and 0.78 pre-Omicron, P = 0.006). At 1.5 years after infection, patients had no clinically meaningful decline in severity of long COVID, and 57% (245/429) of patients failed to improve 1.5 years after infection, with no differences between variants.

CONCLUSION: More than half of patients referred to a Post-COVID Clinic failed to improve in long COVID severity 1.5 years after infection regardless of variants of SARS-CoV-2.}, } @article {pmid37906246, year = {2024}, author = {Constantinidou, F and Sander, A and Bergquist, T and Zimmerman, AS and Kingsley, K}, title = {Strategies to Manage the Thinking and Emotional Difficulties of Long COVID: A Guide for Patients and Families.}, journal = {Archives of physical medicine and rehabilitation}, volume = {105}, number = {9}, pages = {1809-1812}, doi = {10.1016/j.apmr.2023.09.014}, pmid = {37906246}, issn = {1532-821X}, mesh = {Humans ; *COVID-19/psychology ; SARS-CoV-2 ; Emotions ; Post-Acute COVID-19 Syndrome ; Thinking ; Family/psychology ; }, } @article {pmid37906016, year = {2023}, author = {Grist, JT and Collier, GJ and Walters, H and Kim, M and Chen, M and Abu Eid, G and Laws, A and Matthews, V and Jacob, K and Cross, S and Eves, A and Durrant, M and McIntyre, A and Thompson, R and Schulte, RF and Raman, B and Robbins, PA and Wild, JM and Fraser, E and Gleeson, F}, title = {Erratum for: Lung Abnormalities Detected with Hyperpolarized [129]Xe MRI in Patients with Long COVID.}, journal = {Radiology}, volume = {309}, number = {1}, pages = {e239025}, doi = {10.1148/radiol.239025}, pmid = {37906016}, issn = {1527-1315}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid37905031, year = {2023}, author = {VanElzakker, MB and Bues, HF and Brusaferri, L and Kim, M and Saadi, D and Ratai, EM and Dougherty, DD and Loggia, ML}, title = {Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [[11]C]PBR28 PET correlates with vascular disease measures.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37905031}, issn = {2692-8205}, support = {S10 RR019307/RR/NCRR NIH HHS/United States ; R01 DA047088/DA/NIDA NIH HHS/United States ; R21 NS130283/NS/NINDS NIH HHS/United States ; S10 RR023043/RR/NCRR NIH HHS/United States ; S10 RR023401/RR/NCRR NIH HHS/United States ; }, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [[11]C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.}, } @article {pmid37904690, year = {2023}, author = {Sykes, DL and Van der Feltz-Cornelis, CM and Holdsworth, L and Hart, SP and O'Halloran, J and Holding, S and Crooks, MG}, title = {Examining the relationship between inflammatory biomarkers during COVID-19 hospitalization and subsequent long-COVID symptoms: A longitudinal and retrospective study.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {10}, pages = {e1052}, pmid = {37904690}, issn = {2050-4527}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19 ; Retrospective Studies ; Interleukin-6 ; Post-Acute COVID-19 Syndrome ; Myalgia ; Biomarkers ; Hospitalization ; C-Reactive Protein/analysis/metabolism ; Ferritins ; }, abstract = {INTRODUCTION: Long-COVID is a heterogeneous condition with a litany of physical and neuropsychiatric presentations and its pathophysiology remains unclear. Little is known about the association between inflammatory biomarkers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) in the acute phase, and persistent symptoms after hospitalization in COVID-19 patients.

METHODS: IL-6, CRP, troponin-T, and ferritin were analyzed at admission for all patients with COVID-19 between September 1, 2020 to January 10, 2021. Survivors were followed up 3-months following hospital discharge and were asked to report persistent symptoms they experienced. Admission data were retrospectively collected. Independent t-tests and Mann-Whitney U tests were performed.

RESULTS: In a sample of 144 patients (62.5% male, mean Age 62 years [SD = 13.6]) followed up 3 months after hospital discharge, the commonest symptoms reported were fatigue (54.2%), breathlessness (52.8%), and sleep disturbance (37.5%). In this sample, admission levels of IL-6, CRP and ferritin were elevated. However, those reporting myalgia, low mood, and anxiety at follow-up had lower admission levels of IL-6 (34.9 vs. 52.0 pg/mL, p = .043), CRP (83 vs. 105 mg/L, p = .048), and ferritin (357 vs. 568 ug/L, p = .01) respectively, compared with those who did not report these symptoms. Multivariate regression analysis showed that these associations were confounded by gender, as female patients had significantly lower levels of IL-6 and ferritin on admission (29.5 vs. 56.1, p = .03 and 421.5 vs. 589, p = .001, respectively) and were more likely to report myalgia, low mood and anxiety, when compared to males.

CONCLUSIONS: Our data demonstrate that female patients present more often with lower levels of inflammatory biomarkers on admission which are subsequently associated with long-term post-COVID symptoms, such as myalgia and anxiety, in those discharged from hospital with severe COVID-19. Further research is needed into the role of serum biomarkers in post-COVID prognostication.}, } @article {pmid37904110, year = {2023}, author = {McNabb, KC and Bergman, AJ and Smith-Wright, R and Seltzer, J and Slone, SE and Tomiwa, T and Alharthi, A and Davidson, PM and Commodore-Mensah, Y and Ogungbe, O}, title = {"It was almost like it's set up for people to fail" A qualitative analysis of experiences and unmet supportive needs of people with Long COVID.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {2131}, pmid = {37904110}, issn = {1471-2458}, support = {F30 AI165167/AI/NIAID NIH HHS/United States ; F31 NR020588/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/epidemiology ; Social Work ; Workplace ; }, abstract = {BACKGROUND: Almost twenty percent of adults with COVID-19 develop Long COVID, leading to prolonged symptoms and disability. Understanding the supportive needs of people with Long COVID is vital to enacting effective models of care and policies.

DESIGN/METHODS: This qualitative sub-study explored the experiences of people with Long COVID and their unmet needs. Participants enrolled in a larger study to evaluate the post-acute cardiovascular impacts of COVID-19 were invited to participate in subsequent in-depth interviews. Participants were enrolled purposively until saturation at 24 participants. Data were analyzed using thematic content analysis.

RESULTS: Participants focused on adaptations to life with Long COVID and their unmet needs in different life spheres. Three domains, 1) occupational and financial; 2) healthcare-related; and 3) social and emotional support, emerged as areas affecting quality of life. Although participants were motivated to return to work for financial and personal reasons, Long COVID symptoms often resulted in the inability to perform tasks required by their existing jobs, and unemployment. Those who maintained employment through employer accommodations still needed additional support. Participants encountered diagnostic challenges, challenges in accessing specialty appointments, insurance loopholes, high healthcare costs, and medical skepticism. Existing social networks provided support for completing daily tasks; however, those with Long COVID typically turned to others with similar lived experiences for emotional support. Participants found government support programs inadequate and difficult to access in all three domains.

DISCUSSION: We propose a five-pronged policy approach to support persons with Long COVID. These overarching recommendations are (1) improve public awareness of Long COVID; (2) improve clinical care quality and access; (3) implement additional school and workplace accommodations; (4) strengthen socioeconomic benefits and social services; and (5) improve research on Long COVID.}, } @article {pmid37903614, year = {2024}, author = {Chen, EY and Morrow, AK and Malone, LA}, title = {Exploring the Influence of Preexisting Conditions and Infection Factors on Pediatric Long COVID Symptoms and Quality of Life.}, journal = {American journal of physical medicine & rehabilitation}, volume = {103}, number = {7}, pages = {567-574}, doi = {10.1097/PHM.0000000000002363}, pmid = {37903614}, issn = {1537-7385}, mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Quality of Life ; Male ; Female ; Child ; Retrospective Studies ; *Post-Acute COVID-19 Syndrome ; Adolescent ; *SARS-CoV-2 ; Fatigue ; Child, Preschool ; Depression/psychology/epidemiology ; }, abstract = {OBJECTIVE: Pediatric postacute sequelae of SARS-CoV-2 or "long COVID" is a multisystemic disease with a wide range of symptoms more than 4 wks after initial infection. This study explores the quality of life in children with long COVID and how preexisting conditions affect symptoms and quality of life.

DESIGN: A retrospective single-center study of 97 patients was completed to analyze PedsQL quality of life in pediatric patients with long COVID and associations between preexisting conditions, long COVID symptoms, and PedsQL scores.

RESULTS: Children with long COVID had significantly lower quality of life compared with previously published normative samples (PedsQL Core: P < 0.001; Fatigue: P < 0.001; Family Impact: P < 0.001). Number of long COVID symptoms, age, and preexisting history of depression, allergies, and developmental delay affected the overall fatigue PedsQL scores. Preexisting mood disorders were associated with a higher prevalence of worsening mental health symptoms (anxiety, P = 0.01; depression, P = 0.04), dizziness/lightheadedness/vertigo (P = 0.02), and change in appetite (P = 0.04).

CONCLUSIONS: Long COVID has a significant impact on the quality of life of children and their families. Children with long COVID can benefit from multidisciplinary care addressing fatigue, mental health, and family coping.}, } @article {pmid37901401, year = {2023}, author = {Westermeier, F and Sepúlveda, N}, title = {Editorial: Reproducibility and rigour in infectious diseases - surveillance, prevention and treatment.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1294969}, pmid = {37901401}, issn = {2296-858X}, } @article {pmid37900449, year = {2023}, author = {Salve, HR and Daniel, RA and Kumar, A and Kumar, R and Misra, P}, title = {Prevalence and Determinants of Long COVID Among Patients Attending the Outpatient Department of a Subdistrict Hospital in Haryana.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e46007}, pmid = {37900449}, issn = {2168-8184}, abstract = {INTRODUCTION: Growing evidence indicates that individuals recovering from COVID-19 may experience prolonged health consequences, resulting in notable morbidity even after the acute phase. Limited published literature exists concerning sequelae of COVID-19 among the Indian population. Therefore, we conducted this study at a subdistrict hospital (secondary level) in Haryana, aiming to estimate the prevalence of long COVID and its determinants.

METHODS: This hospital-based study focused on outpatients who had a confirmed history of COVID-19, with a minimum of 28 days elapsed since the positive COVID-19 diagnostic test date. We administered a semi-structured questionnaire to gather sociodemographic information, a standardized symptom assessment checklist to identify long COVID symptoms, and the Patient Health Questionnaire (PHQ-9) to evaluate and grade depression severity. Additionally, we conducted pulmonary function tests, chest X-rays, complete blood counts, and kidney and liver function tests to assess the determinants of long COVID. STATA version 14 software (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP) was used for data analysis, and the bivariate and multivariate analyses (p-value <0.2 in bivariate analysis) were conducted to determine factors associated with long COVID.

RESULTS: A total of 212 participants (male 53%) were recruited in this study. Among the long COVID symptoms, fatigue, body pain, cough, joint pain, and breathlessness were the most frequently reported symptoms among the study participants. The prevalence of long COVID was found to be 37.3% (95%CI: 30.7-43.8%). In the multivariate model, depression (PHQ-9 scores) AOR-1.21 (95%CI:1.07-1.35) and severity of COVID-19 adjusted odds ratio (AOR)-2.22 (95%CI:1.05-4.69) came out to be statistically significant with long COVID.

CONCLUSION: Findings show alarming rates of long COVID symptoms persisting in nearly 37% of COVID-19-recovered individuals. Establishing tailored guidelines is crucial to mitigate burdens and complications and enhance the quality of life for those affected.}, } @article {pmid37899735, year = {2023}, author = {Evered, JA and LaJeunesse, A and Wynn, M and Mrig, E and Schlesinger, M and Grob, R}, title = {Gaps in benefits, awareness, and comprehension that leave those with long COVID vulnerable.}, journal = {Chronic illness}, volume = {}, number = {}, pages = {17423953231210117}, pmid = {37899735}, issn = {1745-9206}, support = {R01 HG011792/HG/NHGRI NIH HHS/United States ; }, abstract = {OBJECTIVES: The COVID-19 pandemic has left many suffering from long COVID, an episodic and debilitating chronic condition affecting people's ability to work and manage medical expenses. Though the Biden Administration has committed to conducting research and building support programs to alleviate the strain on those affected, in practice, static eligibility criteria for unemployment and disability benefits, patchy insurance coverage, and insufficient paid leave programs have left many people vulnerable. Given the magnitude of long COVID and the dearth to date of large-scale studies about its financial consequences, a focused qualitative analysis of lived experiences is warranted to understand and highlight gaps in the policy landscape.

METHODS: We conducted in-depth semi-structured interviews from 2020 to 2022 with 25 people with experience of long COVID living predominately in the Midwest.

RESULTS: Our inductive analysis revealed ways people became financially exhausted by uncertain medical care costs and precarious employment that left them trying, often alone, to access benefits. People described both experiences with workplace benefits and attempts to access federal benefits to address unstable employment situations created by protracted and uncertain functional impairments.

DISCUSSION: We explore pre- and post-pandemic era unemployment, disability, and insurance policies and offer recommendations for better supporting people with long COVID.}, } @article {pmid37898059, year = {2023}, author = {Chinvararak, C and Chalder, T}, title = {Prevalence of sleep disturbances in patients with long COVID assessed by standardised questionnaires and diagnostic criteria: A systematic review and meta-analysis.}, journal = {Journal of psychosomatic research}, volume = {175}, number = {}, pages = {111535}, doi = {10.1016/j.jpsychores.2023.111535}, pmid = {37898059}, issn = {1879-1360}, mesh = {Humans ; Male ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; *Sleep Wake Disorders/diagnosis/epidemiology/etiology ; Sleep ; COVID-19 Testing ; }, abstract = {OBJECTIVE: We aimed to study the prevalence of sleep disturbances in patients with long COVID-19.

METHODS: We conducted a systematic review and meta-analysis of the pooled prevalence of sleep disturbances in patients post COVID-19. We systematically searched relevant studies from three databases, including Medline, Embase and Scopus. Original articles were included based on specific criteria: peer-reviewed, observational studies involving adults (18 or older) with confirmed post COVID-19 status through PCR testing and focused on sleep in the context of post COVID-19. Exclusion criteria included non-English articles, studies with insufficient data, and narrative/systematic reviews. The search was performed from 31st July 2023 to 15th August 2023. We identified 35 eligible papers; however, we excluded 6 studies which did not describe the sleep assessment. We used a random-effects meta-analysis model to estimate the pooled prevalence of sleep disturbances.

RESULTS: 29 studies involved 13,935 long COVID-19 patients; approximately 39% of participants were male aged 18 to 97 years. The overall pooled prevalence of sleep disturbance was 46% (95% CI: 38-54%). Subgroup analyses revealed that the pooled prevalence of poor sleep quality was 56% (95% CI: 47-65%). The pooled prevalence of insomnia was 38% (95% CI: 28-48%). Finally, the pooled prevalence of excessive daytime sleepiness was 14% (95% CI: 0-29%).

CONCLUSION: Sleep disturbances are common in long COVID-19 patients. The healthcare sector should recognise these sleep issues and provide an early, effective treatment to prevent long-term sequelae of sleep problems.}, } @article {pmid37897034, year = {2023}, author = {Koleničová, V and Vňuková, MS and Anders, M and Fišerová, M and Raboch, J and Ptáček, R}, title = {A Review Article on Exercise Intolerance in Long COVID: Unmasking the Causes and Optimizing Treatment Strategies.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {29}, number = {}, pages = {e941079}, pmid = {37897034}, issn = {1643-3750}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; Cognitive Training ; Fatigue/etiology/therapy ; }, abstract = {There is a growing body of research on SARS-CoV-2 (PASC), previously known as the post-COVID syndrome, a chronic condition characterized by symptoms that persist after SARS-CoV-2 infection. Among these symptoms, feelings of physical exhaustion and prolonged fatigue are particularly prevalent and can significantly impact patients' quality of life. These symptoms are associated with reduced overall physical capacity, decreased daily physical activity, malaise after intense training, and intolerance to physical activity (IFA). IFA, described as a reduced ability to perform physical activities typical for the patient's age, can often lead to a sedentary lifestyle. Prolonged physical inactivity can cause deterioration in the overall physical condition and disrupt mitochondrial function, triggering a vicious cycle of gradual symptom worsening. The underlying causes of PASC remain unclear; however, several biochemical mechanisms have been discussed to explain the body's energy depletion, and a multidisciplinary approach that combines physical and cognitive rehabilitation and lifestyle interventions such as exercise and diet modifications has been suggested to improve the overall health and well-being of PASC patients. This critical review aims to review the existing research on the possible causes and links among chronic fatigue, reduced physical activity, and exercise intolerance in patients with PASC. Further research into the underlying causes and treatment of PASC and the importance of developing individualized treatment is needed to address each patient's unique health requirements.}, } @article {pmid37896992, year = {2023}, author = {Domènech-Montoliu, S and Puig-Barberà, J and Badenes-Marques, G and Gil-Fortuño, M and Orrico-Sánchez, A and Pac-Sa, MR and Perez-Olaso, O and Sala-Trull, D and Sánchez-Urbano, M and Arnedo-Pena, A}, title = {Long COVID Prevalence and the Impact of the Third SARS-CoV-2 Vaccine Dose: A Cross-Sectional Analysis from the Third Follow-Up of the Borriana Cohort, Valencia, Spain (2020-2022).}, journal = {Vaccines}, volume = {11}, number = {10}, pages = {}, pmid = {37896992}, issn = {2076-393X}, support = {NA//Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana/ ; NA//Consellería de Sanitat Universal i Salut Pública/ ; }, abstract = {BACKGROUND: In March 2020, a COVID-19 outbreak linked to mass gathering dinners at the Falles Festival in Borriana, Spain, resulted in an estimated attack rate of 42.6% among attendees.

METHODS: In June 2022, we conducted a cross-sectional follow-up study of 473 adults aged 18 to 64 who attended the dinners at the Falles Festival in 2020, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse-probability weighting analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count.

RESULTS: A total of 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Long COVID diagnosis was less likely with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ-producing-CD8+ response, and infection during the Omicron period. Increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection were associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56% to 92%) and symptom count by 55% (95% CI: 32% to 79%).

CONCLUSION: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination's role in mitigating SARS-CoV-2 infection consequences.}, } @article {pmid37896973, year = {2023}, author = {Qin, C and Deng, J and Du, M and Liu, Q and Wang, Y and Yan, W and Liu, M and Liu, J}, title = {Pandemic Fatigue and Vaccine Hesitancy among People Who Have Recovered from COVID-19 Infection in the Post-Pandemic Era: Cross-Sectional Study in China.}, journal = {Vaccines}, volume = {11}, number = {10}, pages = {}, pmid = {37896973}, issn = {2076-393X}, support = {72122001//National Natural Science Foundation of China/ ; L222027//Beijing Natural Science Foundation/ ; }, abstract = {At present, the COVID-19 pandemic is still ongoing globally and the virus is constantly mutating. The herd immunity barrier established by past infections or vaccinations is gradually weakening and reinfections are occurring. To evaluate the pandemic fatigue and vaccine hesitancy among people who have recovered from COVID-19 in the post-pandemic era, we conducted an anonymous cross-sectional survey study in China from 4 July to 11 August 2023, nearly 6 months after the last large-scale nationwide infection. Basic sociodemographic characteristics, health-related factors (smoking, drinking, and chronic disease history), COVID-19 vaccination history, and self-reported long COVID were obtained as potential covariates. A series of logistic regression models were performed to examine the association between pandemic fatigue and vaccine hesitancy toward the next dose of COVID-19 vaccines via crude relative risks (cORs) and adjusted relative risks (aORs) with 95% CIs. According to our results, of the 2942 participants, 1242 (42.2%) were hesitant (unwilling or not sure) to receive the next dose of COVID-19 vaccines. The average score on the Pandemic Fatigue Scale was 21.67 ± 8.86, in which the scores of all items in the vaccine-hesitant group were significantly higher than those in the vaccine-accepting group. Additionally, the higher the pandemic fatigue level among people who have recovered from COVID-19, the more likely they were to be hesitant to receive the next dose of the COVID-19 vaccines (moderate: aOR = 2.94, 95% CI: 2.46-3.53; high: aOR = 6.88, 95% CI: 5.49-8.64). Overall, more than 40% of the recovered participants were unwilling or uncertain about the next vaccine dose, with varying degrees of pandemic fatigue. Pandemic fatigue is a potentially relevant factor for vaccine hesitancy and may hinder the translation of vaccination intention into behavior. Considering the ongoing reinfection situation, implementing a health education plan to reduce pandemic fatigue and prioritizing vaccination issues for people who have recovered from COVID-19 may be key to promoting the reduction of the COVID-19 disease burden and ensuring the health and well-being of the population.}, } @article {pmid37895148, year = {2023}, author = {Yang, YF and Singh, S}, title = {Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895148}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/genetics ; Antioxidants/therapeutic use ; Post-Acute COVID-19 Syndrome ; Ivermectin/therapeutic use ; Pandemics ; Anthocyanins ; Pharmacogenetics ; *MicroRNAs/genetics ; }, abstract = {COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments.}, } @article {pmid37894116, year = {2023}, author = {Tziolos, NR and Ioannou, P and Baliou, S and Kofteridis, DP}, title = {Long COVID-19 Pathophysiology: What Do We Know So Far?.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894116}, issn = {2076-2607}, abstract = {Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome.}, } @article {pmid37894054, year = {2023}, author = {Alonso-Domínguez, J and Gallego-Rodríguez, M and Martínez-Barros, I and Calderón-Cruz, B and Leiro-Fernández, V and Pérez-González, A and Poveda, E}, title = {High Levels of IL-1β, TNF-α and MIP-1α One Month after the Onset of the Acute SARS-CoV-2 Infection, Predictors of Post COVID-19 in Hospitalized Patients.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894054}, issn = {2076-2607}, support = {P19/00747//Instituto de Investigación Carlos III/ ; PI22/01341//Instituto de Investigación Carlos III/ ; CM20/00243//Instituto de Investigación Carlos III/ ; IN606A-2022//Axencia Galega de Innovación/ ; CI22-A-02//Galicia Sur Biomedical Foundation/ ; }, abstract = {The pandemic caused by SARS-CoV-2 infection has left behind a new symptomatology called post COVID-19, or "long COVID". The pathophysiological mechanisms still remain controversial; however, a link between persistent inflammation and these sequelae has been suggested. Herein, we longitudinally assessed up- and downstream molecules of the NLRP3 inflammasome's pathway in three study groups: healthy donors (HC, n = 14) and donors with a confirmed SARS-CoV-2 infection who had been hospitalized, the latter divided into post COVID-19 (PC, n = 27) and non-post COVID-19 patients (nPC, n = 27) based on the presence or absence of symptomatology at month 6, respectively. Plasma cytokines (IL-1β, IL-3, IL-6, IL-8, IL-18, IP-10, MIG, TNF-α, IFN-γ, MIP-1α and MIP-1β) and total peroxide (TPX) levels were quantified at baseline and at months 1 and 6 after the onset of the infection. Baseline values were the highest for both TPX and cytokines that progressively decreased thereafter the acute infection. IL-1β, MIP-1α and TNF-α at month 1 were the only cytokines that showed a significant difference between nPC and PC. These findings suggest that a persistent inflammatory state one month after the onset of SARS-CoV-2 infection related to specific cytokines (IL-1β, MIP-1α, and TNF-α) might guide to predicting post COVID-19 symptomatology.}, } @article {pmid37893865, year = {2023}, author = {Di Fusco, M and Cappelleri, JC and Anatale-Tardiff, L and Coetzer, H and Yehoshua, A and Alvarez, MB and Allen, KE and Porter, TM and Puzniak, L and Cha-Silva, AS and Lopez, SMC and Sun, X}, title = {Impact of COVID-19 Infection on Health-Related Quality of Life, Work Productivity and Activity Impairment by Symptom-Based Long COVID Status and Age in the US.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {20}, pages = {}, pmid = {37893865}, issn = {2227-9032}, abstract = {COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups.}, } @article {pmid37893239, year = {2023}, author = {Maurel, S and Giménez-Llort, L and Alegre-Martin, J and Castro-Marrero, J}, title = {Hierarchical Cluster Analysis Based on Clinical and Neuropsychological Symptoms Reveals Distinct Subgroups in Fibromyalgia: A Population-Based Cohort Study.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893239}, issn = {2227-9059}, abstract = {Fibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adult FM patients referred to primary care according to the 2010 ACR case criteria. Patients were aggregated in clusters by a K-medians hierarchical cluster analysis based on physical and emotional symptoms and neuropsychological variables. Four different clusters were identified in the FM population. Global cluster analysis reported a four-cluster profile (cluster 1: pain, fatigue, poorer sleep quality, stiffness, anxiety/depression and disability at work; cluster 2: injustice, catastrophizing, positive affect and negative affect; cluster 3: mindfulness and acceptance; and cluster 4: surrender). The second analysis on clinical symptoms revealed three distinct subgroups (cluster 1: fatigue, poorer sleep quality, stiffness and difficulties at work; cluster 2: pain; and cluster 3: anxiety and depression). The third analysis of neuropsychological variables provided two opposed subgroups (cluster 1: those with high scores in surrender, injustice, catastrophizing and negative affect, and cluster 2: those with high scores in acceptance, positive affect and mindfulness). These empirical results support models that assume an interaction between neurobiological, psychological and social factors beyond the classical biomedical model. A detailed assessment of such risk and protective factors is critical to differentiate FM subtypes, allowing for further identification of their specific needs and designing tailored personalized therapeutic interventions.}, } @article {pmid37893078, year = {2023}, author = {Hackshaw, KV and Yao, S and Bao, H and de Lamo Castellvi, S and Aziz, R and Nuguri, SM and Yu, L and Osuna-Diaz, MM and Brode, WM and Sebastian, KR and Giusti, MM and Rodriguez-Saona, L}, title = {Metabolic Fingerprinting for the Diagnosis of Clinically Similar Long COVID and Fibromyalgia Using a Portable FT-MIR Spectroscopic Combined with Chemometrics.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893078}, issn = {2227-9059}, support = {R61 NS117211/NS/NINDS NIH HHS/United States ; R61NS117211/NH/NIH HHS/United States ; }, abstract = {Post Acute Sequelae of SARS-CoV-2 infection (PASC or Long COVID) is characterized by lingering symptomatology post-initial COVID-19 illness that is often debilitating. It is seen in up to 30-40% of individuals post-infection. Patients with Long COVID (LC) suffer from dysautonomia, malaise, fatigue, and pain, amongst a multitude of other symptoms. Fibromyalgia (FM) is a chronic musculoskeletal pain disorder that often leads to functional disability and severe impairment of quality of life. LC and FM share several clinical features, including pain that often makes them indistinguishable. The aim of this study is to develop a metabolic fingerprinting approach using portable Fourier-transform mid-infrared (FT-MIR) spectroscopic techniques to diagnose clinically similar LC and FM. Blood samples were obtained from LC (n = 50) and FM (n = 50) patients and stored on conventional bloodspot protein saver cards. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. Through the deconvolution analysis of the spectral data, a distinct spectral marker at 1565 cm[-1] was identified based on a statistically significant analysis, only present in FM patients. This IR band has been linked to the presence of side chains of glutamate. An OPLS-DA algorithm created using the spectral region 1500 to 1700 cm[-1] enabled the classification of the spectra into their corresponding classes (Rcv > 0.96) with 100% accuracy and specificity. This high-throughput approach allows unique metabolic signatures associated with LC and FM to be identified, allowing these conditions to be distinguished and implemented for in-clinic diagnostics, which is crucial to guide future therapeutic approaches.}, } @article {pmid37893042, year = {2023}, author = {Wallukat, G and Wernike, K and Bachamanda Somesh, D and Mettenleiter, TC and Müller, J}, title = {Animals Experimentally Infected with SARS-CoV-2 Generate Functional Autoantibodies against G-Protein-Coupled Receptors.}, journal = {Biomedicines}, volume = {11}, number = {10}, pages = {}, pmid = {37893042}, issn = {2227-9059}, abstract = {(1) Background: SARS-CoV-2 infection has been linked to diverse clinical manifestations in humans, including cardiovascular complications. Functional autoantibodies targeting G-protein-coupled receptors have emerged as potential contributors to these effects. This study sought to investigate the production and activity of functional autoantibodies targeting G-protein-coupled receptors after SARS-CoV-2 infection of selected animal species. (2) Methods: The presence of functional autoantibodies such as 2-adrenoceptor, angiotensin II AT1 receptor, muscarinic M2 receptor, and angiotensin 1-7 MAS receptor was assessed in cattle and ferrets experimentally infected with SARS-CoV-2. Bioassays were conducted to evaluate the positive or negative chronotropic responses induced by these autoantibodies. Further experiments identified the extracellular domains to which the functional autoantibodies bind, and receptor antagonists were employed to block the induced responses. (3) Results: Only two out of six cattle that were inoculated with SARS-CoV-2 displayed viral replication and tested positive for functional autoantibodies against G-protein-coupled receptors. These functional autoantibodies specifically recognized β2-adrenoceptor, angiotensin II AT1 receptor, muscarinic M2 receptor, and angiotensin 1-7 MAS receptor and induced distinct positive and negative chronotropic effects in the bioassay. Infected ferrets generated functional autoantibodies against β2-adrenoceptor and muscarinic M2 receptor and presented bioactivity similar to that in cattle. (4) Conclusions: This study uncovers functional autoantibodies targeting G-protein-coupled receptors in cattle and ferrets post-SARS-CoV-2 infection, with implications for cardiovascular function.}, } @article {pmid37892724, year = {2023}, author = {Carrasco-Garrido, P and Palacios-Ceña, D and Hernández-Barrera, V and Jiménez-Trujillo, I and Gallardo-Pino, C and Fernández-de-Las-Peñas, C}, title = {Patterns of Opioid and Non-Opioid Analgesic Consumption in Patients with Post-COVID-19 Conditions.}, journal = {Journal of clinical medicine}, volume = {12}, number = {20}, pages = {}, pmid = {37892724}, issn = {2077-0383}, support = {Grant/Award Number: 2014-2020//Recursos REACT-UE del Programa Operativo de Madrid, Grant/Award Number: 2014-2020; Comunidad de Madrid y la Unión Europea./ ; }, abstract = {Pain is a major health issue for healthcare systems, and access to pain treatment is a fundamental human right. Pain is a common symptom experienced in the post-COVID phase by a significant percentage of patients. This study describes the prevalence and associated factors associated with the use of opioid and non-opioid analgesics in subjects with post-COVID-19 condition. Sociodemographic data, post-COVID symptoms, health profile, and opioid and non-opioid analgesic consumption were collected in 390 subjects with post-COVID-19 condition. We analyzed the independent effect of all variables on opioid/non-opioid analgesic consumption by using logistic multivariate regressions. The prevalence of opioid and non-opioid analgesic consumption was 24.1% and 82.3%, respectively. Tramadol (17.18%) and codeine (7.95%) were the most commonly used opioid analgesics, and Paracetamol (70%) and ibuprofen (45.4%) were the most commonly used non-opioid analgesics. Females were more likely to consume non-opioid analgesics (aOR2.20, 95%CI 1.15, 4.22) than males. Marital status of married/partner vs. single (aOR2.96; 95% CI 1.43, 6.12), monthly income < EUR 1000 VS. > EUR 2000 (aOR3.81; 95% CI 1.37, 10.61), number of post-COVID symptoms < 5 (aOR2.64, 95%CI 1.18, 5.87), and anxiolytics consumption (aOR 1.85, 95%CI 1.05, 3.25) were associated with a greater likelihood of opioid analgesic consumption. Age > 55 years (aOR3.30, 95%CI 1.34, 8.09) and anxiolytics consumption (aOR2.61, 95%CI 1.36, 4.98) were associated with a greater likelihood of non-opioid analgesic consumption. Opioid analgesic consumption was highly associated (aOR 3.41, 95%CI 1.27, 6.11) with non-opioid analgesic consumption. The prevalence of opioid analgesic and non-opioid analgesic consumption in individuals with post-COVID-19 condition was 24.1% and 82.3%. Females with post-COVID-19 condition showed higher non-opioid analgesic consumption than men. Predictors of opioid consumption were marital status, lower monthly income, number of post-COVID symptoms, and anxiolytic consumption. Older age and anxiolytic consumption were predictors of non-opioid consumption.}, } @article {pmid37892676, year = {2023}, author = {Abdulan, IM and Feller, V and Oancea, A and Maștaleru, A and Alexa, AI and Negru, R and Cumpăt, CM and Leon, MM}, title = {Evolution of Cardiovascular Risk Factors in Post-COVID Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {20}, pages = {}, pmid = {37892676}, issn = {2077-0383}, abstract = {(1) Background: SARS-CoV-2 infection has been a subject of extensive discussion in the medical field, particularly in relation to the risk factors and effective treatment strategies for reducing the negative health outcomes associated with the virus. However, researchers indicate that individuals in the recovery phase after COVID-19 experience a range of symptoms that significantly impact their overall well-being and quality of life. At present, there is insufficient evidence to substantiate the claim that patients in the post-acute phase of COVID-19 are at an elevated risk of developing new-onset hypertension or even metabolic syndrome. The current study aimed to assess the risk of cardiovascular diseases after COVID-19 and the optimal treatment of these conditions. (2) Methods: This research was conducted at the Cardiovascular Rehabilitation Clinic of the Iasi Clinical Rehabilitation Hospital (Romania) between the 1st of September and 31st of December 2022. From a total of 551 patients hospitalized in that period, 70 patients with multiple comorbidities were selected. This study included patients over 18 years old who were diagnosed with COVID-19 within the past 30 days. (3) Results: The included patients were mostly women (62.9%) from the urban area (61.4%). Comparing the post-COVID-19 period to the pre-COVID-19 one, it was observed that the risk of hypertension increased from 69.57% to 90% among the subjects (p = 0.005). Risk factors for the new onset of hypertension were identified as age, female gender, and an elevated body mass index. Moreover, the number of patients with dyslipidemia doubled, and a higher body mass index was noted. (4) Conclusions: Our findings suggest that patients affected by COVID-19 are at an increased risk of developing hypertension and related disorders.}, } @article {pmid37892261, year = {2023}, author = {Körner, RW and Bansemir, OY and Franke, R and Sturm, J and Dafsari, HS}, title = {Atopy and Elevation of IgE, IgG3, and IgG4 May Be Risk Factors for Post COVID-19 Condition in Children and Adolescents.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {10}, pages = {}, pmid = {37892261}, issn = {2227-9067}, support = {413543196//Cologne Clinician Scientist Program / Medical Faculty / University of Cologne and German Research Foundation/ ; }, abstract = {SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenotypes with increasing prevalence. Its manifestation and risk factors remain elusive. In this monocentric study, we hypothesized that atopy, the tendency to produce an exaggerated immunoglobulin E (IgE) immune response, is a risk factor for the manifestation of pediatric PCC. We present a patient cohort (n = 28) from an early pandemic period (2021-2022) with comprehensive evaluations of phenotypes, pulmonary function, and molecular investigations. PCC predominantly affected adolescents and presented with fatigue, dyspnea, and post-exertional malaise. Sensitizations to aeroallergens were found in 93% of cases. We observed elevated IgE levels (mean 174.2 kU/L, reference < 100 kU/L) regardless of disease severity. Concurrent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was found in 29% of patients that also faced challenges in school attendance. ME/CFS manifestation was significantly associated with elevated immunoglobulin G subclasses IgG3 (p < 0.05) and IgG4 (p < 0.05). A total of 57% of patients showed self-limiting disease courses with mean recovery at 12.7 months (range 5-25 months), 29% at 19.2 months (range 12-30 months), and the rest demonstrated overall improvement. These findings offer additional insights into immune dysregulation as a risk factor for pediatric PCC.}, } @article {pmid37892009, year = {2023}, author = {Cañadas, P and Gonzalez-Vides, L and Alberquilla García-Velasco, M and Arriola, P and Guemes-Villahoz, N and Hernández-Verdejo, JL}, title = {Neuroinflammatory Findings of Corneal Confocal Microscopy in Long COVID-19 Patients, 2 Years after Acute SARS-CoV-2 Infection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {20}, pages = {}, pmid = {37892009}, issn = {2075-4418}, abstract = {OBJECTIVE: To describe corneal confocal microscopy findings in patients with long COVID-19 with persistent symptoms over 20 months after SARS-CoV-2 infection.

DESIGN: A descriptive cross-sectional study that included a total of 88 patients; 60 patients with Long COVID-19 and 28 controls. Long COVID-19 diagnosis was established according to the World Health Organization criteria. Corneal confocal microscopy using a Heidelberg Retina Tomograph II (Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate sub-basal nerve plexus morphology (corneal nerve fiber density, nerve fiber length, nerve branch density, nerve fiber total branch density, nerve fiber area, and nerve fiber width). Dendritic cell density and area, along with microneuromas and other morphological changes of the nerve fibers were recorded.

RESULTS: Long COVID-19 patients presented with reduced corneal nerve density and branch density as well as shorter corneal nerves compared to the control group. Additionally, Long COVID-19 patients showed an increased density of dendritic cells also with a greater area than that found in the control group of patients without systemic diseases. Microneuromas were detected in 15% of Long COVID-19 patients.

CONCLUSIONS: Long COVID-19 patients exhibited altered corneal nerve parameters and increased DC density over 20 months after acute SARS-CoV-2 infection. These findings are consistent with a neuroinflammatory condition hypothesized to be present in patients with Long COVID-19, highlighting the potential role of corneal confocal microscopy as a promising noninvasive technique for the study of patients with Long COVID-19.}, } @article {pmid37890507, year = {2024}, author = {Kronstein-Wiedemann, R and Tausche, K and Kolditz, M and Teichert, M and Thiel, J and Koschel, D and Tonn, T and Künzel, SR}, title = {Long-COVID is Associated with Impaired Red Blood Cell Function.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {56}, number = {4}, pages = {318-323}, doi = {10.1055/a-2186-8108}, pmid = {37890507}, issn = {1439-4286}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Erythrocytes ; Iron ; Hemoglobins ; Oxygen ; }, abstract = {COVID-19 disease, caused by the severe acute respiratory syndrome virus 2 (SARS-CoV-2), induces a broad spectrum of clinical symptoms ranging from asymptomatic cases to fatal outcomes. About 10-35% of all COVID-19 patients, even those with mild COVID-19 symptoms, continue to show symptoms, i. e., fatigue, shortness of breath, cough, and cognitive dysfunction, after initial recovery. Previously, we and others identified red blood cell precursors as a direct target of SARS-CoV-2 and suggested that SARS-CoV-2 induces dysregulation in hemoglobin- and iron-metabolism contributing to the severe systemic course of COVID-19. Here, we put particular emphasis on differences in parameters of clinical blood gas analysis and hematological parameters of more than 20 healthy and Long-COVID patients, respectively. Long-COVID patients showed impaired oxygen binding to hemoglobin with concomitant increase in carbon monoxide binding. Hand in hand with decreased plasma iron concentration and transferrin saturation, mean corpuscular hemoglobin was elevated in Long-COVID patients compared to healthy donors suggesting a potential compensatory mechanism. Although blood pH was within the physiological range in both groups, base excess- and bicarbonate values were significantly lower in Long-COVID patients. Furthermore, Long-COVID patients displayed reduced lymphocyte levels. The clinical relevance of these findings, e. g., as a cause of chronic immunodeficiency, remains to be investigated in future studies. In conclusion, our data suggest impaired erythrocyte functionality in Long-COVID patients, leading to diminished oxygen supply. This in turn could be an explanation for the CFS, dyspnea and anemia. Further investigations are necessary to identify the underlying pathomechanisms.}, } @article {pmid37890487, year = {2023}, author = {Wang, K and Khoramjoo, M and Srinivasan, K and Gordon, PMK and Mandal, R and Jackson, D and Sligl, W and Grant, MB and Penninger, JM and Borchers, CH and Wishart, DS and Prasad, V and Oudit, GY}, title = {Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID.}, journal = {Cell reports. Medicine}, volume = {4}, number = {11}, pages = {101254}, pmid = {37890487}, issn = {2666-3791}, support = {R01 EY025383/EY/NEI NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Convalescence ; Multiomics ; *COVID-19 ; Biomarkers ; Phenotype ; }, abstract = {The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 months following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed of 20 molecules involved in regulating T cell exhaustion and energy metabolism that can reliably predict adverse clinical outcomes following discharge from acute infection with 83% accuracy and an area under the curve (AUC) of 0.96. Our study reveals pertinent biological processes during convalescence that differ from acute infection, and it supports the development of specific therapies and biomarkers for patients suffering from long COVID.}, } @article {pmid37890484, year = {2023}, author = {Turner, L and Martinez, JR and Najjar, S and Rajapaksha Arachchilage, T and Wang, JC}, title = {Businesses marketing purported stem cell treatments and exosome therapies for COVID-19: An analysis of direct-to-consumer online advertising claims.}, journal = {Stem cell reports}, volume = {18}, number = {11}, pages = {2010-2015}, pmid = {37890484}, issn = {2213-6711}, mesh = {Humans ; United States ; Advertising ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Exosomes ; Marketing ; Stem Cells ; }, abstract = {We identified 38 businesses advertising purported stem cell interventions and exosome products for COVID-19. These companies operated or facilitated access to 60 clinics. More than 75% of these clinics were based in the United States and Mexico. Thirty-six of the businesses marketed their stem cell and exosome products as treatments for Long COVID, six advertised them as "immune boosters," five claimed to treat patients in the acute infection phase, and two claimed their products were preventive. The least expensive product cost $2,950, the most expensive was $25,000, and the average listed cost for patients was $11,322. The promotion of these products is concerning because they have not been approved by national regulators and do not appear to be supported by convincing safety and efficacy data.}, } @article {pmid37890221, year = {2023}, author = {Moyo, E and Chimene, M and Moyo, P and Musuka, G and Mangoya, D and Murewanhema, G and Dzinamarira, T}, title = {Risk factors and clinical presentations of long COVID in Africa: A scoping review.}, journal = {Journal of infection and public health}, volume = {16}, number = {12}, pages = {1982-1988}, doi = {10.1016/j.jiph.2023.09.021}, pmid = {37890221}, issn = {1876-035X}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Case-Control Studies ; Cross-Sectional Studies ; Prospective Studies ; Risk Factors ; }, abstract = {COVID-19-related complications can last for years, even in patients who are asymptomatic during the acute phase, a phenomenon referred to as long COVID. This scoping review aimed to summarize the risk factors and clinical symptoms of long COVID in Africa between 2020 and 2022. Five studies were included. Three of the studies used in this review were retrospective cross-sectional studies, one was a prospective cohort study while another one was a case-control study. The review identified several risk factors for long COVID, including being female, being older than 40 years, having more than four acute COVID-19 symptoms, and having concomitant conditions such as asthma, hypertension, and depression. General, respiratory, cardiovascular, otolaryngological, gastrointestinal, and neurological symptoms were among the reported long COVID symptoms. To ensure that patients with long COVID are diagnosed and treated early, the risk factors and clinical symptoms of long COVID need to be identified for different population groups.}, } @article {pmid37889567, year = {2024}, author = {Kim, M and Hwang, J and Grist, JT and Abueid, G and Yoon, SH and Grau, V and Fraser, E and Gleeson, FV}, title = {Functional Impairment in Small Airways Associated With the Breathlessness Symptoms in Long-Coronavirus Disease.}, journal = {Journal of thoracic imaging}, volume = {39}, number = {2}, pages = {79-85}, doi = {10.1097/RTI.0000000000000748}, pmid = {37889567}, issn = {1536-0237}, mesh = {Humans ; *Xenon Isotopes ; *Post-Acute COVID-19 Syndrome ; Lung/diagnostic imaging/pathology ; Respiration ; Magnetic Resonance Imaging/methods ; Dyspnea/diagnostic imaging ; }, abstract = {PURPOSE: This study aimed to determine the association between functional impairment in small airways and symptoms of dyspnea in patients with Long-coronavirus disease (COVID), using imaging and computational modeling analysis.

PATIENTS AND METHODS: Thirty-four patients with Long-COVID underwent thoracic computed tomography and hyperpolarized Xenon-129 magnetic resonance imaging (HP Xe MRI) scans. Twenty-two answered dyspnea-12 questionnaires. We used a computed tomography-based full-scale airway network (FAN) flow model to simulate pulmonary ventilation. The ventilation distribution projected on a coronal plane and the percentage lobar ventilation modeled in the FAN model were compared with the HP Xe MRI data. To assess the ventilation heterogeneity in small airways, we calculated the fractal dimensions of the impaired ventilation regions in the HP Xe MRI and FAN models.

RESULTS: The ventilation distribution projected on a coronal plane showed an excellent resemblance between HP Xe MRI scans and FAN models (structure similarity index: 0.87 ± 0.04). In both the image and the model, the existence of large clustered ventilation defects was not identifiable regardless of dyspnea severity. The percentage lobar ventilation of the HP Xe MRI and FAN model showed a strong correlation (ρ = 0.63, P < 0.001). The difference in the fractal dimension of impaired ventilation zones between the low and high dyspnea-12 score groups was significant (HP Xe MRI: 1.97 [1.89 to 2.04] and 2.08 [2.06 to 2.14], P = 0.005; FAN: 2.60 [2.59 to 2.64] and 2.64 [2.63 to 2.65], P = 0.056).

CONCLUSIONS: This study has identified a potential association of small airway functional impairment with breathlessness in Long-COVID, using fractal analysis of HP Xe MRI scans and FAN models.}, } @article {pmid37889495, year = {2024}, author = {Kuut, TA and Müller, F and Csorba, I and Braamse, AMJ and Nieuwkerk, P and Rovers, CP and Knoop, H}, title = {Positive Effects of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following COVID-19 Are Sustained Up to 1 Year After Treatment.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {78}, number = {4}, pages = {1078-1079}, doi = {10.1093/cid/ciad661}, pmid = {37889495}, issn = {1537-6591}, support = {/ZONMW_/ZonMw/Netherlands ; }, mesh = {Humans ; *COVID-19 ; Fatigue/etiology/therapy ; *Fatigue Syndrome, Chronic ; *Cognitive Behavioral Therapy ; Treatment Outcome ; }, } @article {pmid37888141, year = {2023}, author = {Saleh, SAK and Adly, HM}, title = {Impact of Ambient Air Pollution Exposure on Long COVID-19 Symptoms: A Cohort Study within the Saudi Arabian Population.}, journal = {Infectious disease reports}, volume = {15}, number = {5}, pages = {642-661}, pmid = {37888141}, issn = {2036-7430}, abstract = {UNLABELLED: Evidence suggests that air pollution, specifically the particulate matters PM2.5 and PM10, plays a key role in exacerbating the risk of prolonged symptoms following COVID-19 infection.

AIM: This study endeavors to elucidate the potential interaction between chronic air pollution exposure and the manifestation of long COVID symptoms within a cohort based in Makkah, Saudi Arabia.

METHODS: Participants included residents from the Makkah region who had recovered from COVID-19 between 2022 and 2023. A comprehensive questionnaire was utilized to gather detailed demographic data and assess the persistent symptoms seen during the post-COVID period. To gauge the environmental exposure to potential risk factors, air sampling for PM10 and PM2.5 was systematically conducted in various locations in Makkah over a year.

RESULTS: Significant positive associations were found between PM2.5 and PM10 exposure and long COVID. Furthermore, specific symptom analysis revealed a significant association between air pollution and shortness of breath (for PM2.5). Only PM2.5 exposure remained statistically significant (RR = 1.32, 95% CI: 1.05, 1.67). In contrast, the association with PM10 remained on the cusp of significance, with an RR of 1.27 (95% CI: 1.00, 1.61).

CONCLUSION: This study highlights the importance of reducing air pollution levels to mitigate the long-term health consequences of COVID-19.}, } @article {pmid37887751, year = {2023}, author = {Fernández-de-Las-Peñas, C and Guijarro, C and Torres-Macho, J and Pellicer-Valero, OJ and Franco-Moreno, A and Nijs, J and Velasco-Arribas, M}, title = {Serological Biomarkers at Hospital Admission and Hospitalization Treatments Are Not Related to Sensitization-Associated Symptoms in Patients with Post-COVID Pain.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37887751}, issn = {2076-0817}, support = {LONG-COVID-EXP-CM//Consejería de Economía, Empleo y Competitividad Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.}, } @article {pmid37887357, year = {2023}, author = {Mrakic-Sposta, S and Vezzoli, A and Garetto, G and Paganini, M and Camporesi, E and Giacon, TA and Dellanoce, C and Agrimi, J and Bosco, G}, title = {Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes.}, journal = {Metabolites}, volume = {13}, number = {10}, pages = {}, pmid = {37887357}, issn = {2218-1989}, abstract = {Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.}, } @article {pmid37886846, year = {2023}, author = {Rodríguez-Del-Río, FJ and Barroso, P and Fernández-de-Mera, IG and de la Fuente, J and Gortázar, C}, title = {COVID-19 epidemiology and rural healthcare: a survey in a Spanish village.}, journal = {Epidemiology and infection}, volume = {151}, number = {}, pages = {e188}, pmid = {37886846}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/epidemiology ; Rural Population ; SARS-CoV-2 ; Retrospective Studies ; Delivery of Health Care ; }, abstract = {We used primary care data to retrospectively describe the entry, spread, and impact of COVID-19 in a remote rural community and the associated risk factors and challenges faced by the healthcare team. Generalized linear models were fitted to assess the relationship between age, sex, period, risk group status, symptom duration, post-COVID illness, and disease severity. Social network and cluster analyses were also used. The first six cases, including travel events and a social event in town, contributed to early infection spread. About 351 positive cases were recorded and 6% of patients experienced two COVID-19 episodes in the 2.5-year study period. Five space-time case clusters were identified. One case, linked with the social event, was particularly central in its contact network. The duration of disease symptoms was driven by gender, age, and risk factors. The probability of suffering severe disease increased with symptom duration and decreased over time. About 27% and 23% of individuals presented with residual symptoms and post-COVID illness, respectively. The probability of developing a post-COVID illness increased with age and the duration of COVID-associated symptoms. Carefully registered primary care data may help optimize infection prevention and control efforts and upscale local healthcare capacities in vulnerable rural communities.}, } @article {pmid37885796, year = {2023}, author = {Pagen, DME and van Bilsen, CJA and Brinkhues, S and Van Herck, M and Konings, K and den Heijer, CDJ and Ter Waarbeek, HLG and Spruit, MA and Hoebe, CJPA and Dukers-Muijrers, NHTM}, title = {Prevalence of Long-term Symptoms Varies When Using Different Post-COVID-19 Definitions in Positively and Negatively Tested Adults: The PRIME Post-COVID Study.}, journal = {Open forum infectious diseases}, volume = {10}, number = {10}, pages = {ofad471}, pmid = {37885796}, issn = {2328-8957}, abstract = {BACKGROUND: Long-term symptoms after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ie, post-coronavirus disease 2019 [COVID-19] condition or long COVID) constitute a substantial public health problem. Yet, the prevalence remains currently unclear as different case definitions are used, and negatively tested controls are lacking. We aimed to estimate post-COVID-19 condition prevalence using 6 definitions.

METHODS: The Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study is a population-based sample of COVID-19-tested adults. In 2021, 61 655 adults were invited to complete an online questionnaire, including 44 symptoms plus a severity score (0-10) per symptom. Prevalence was calculated in both positively and negatively tested adults, stratified by time since their COVID-19 test (3-5, 6-11, or ≥12 months ago).

RESULTS: In positive individuals (n = 7405, 75.6%), the prevalence of long-term symptoms was between 26.9% and 64.1% using the 6 definitions, while in negative individuals (n = 2392, 24.4%), the prevalence varied between 11.4% and 32.5%. The prevalence of long-term symptoms potentially attributable to COVID-19 ranged from 17.9% to 26.3%.

CONCLUSIONS: There is a (substantial) variation in prevalence estimates when using different post-COVID-19 condition definitions, as is current practice; there is limited overlap between definitions, indicating that the essential post-COVID-19 condition criteria are still unclear. Including negatives is important to determine long-term symptoms attributable to COVID-19.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05128695.}, } @article {pmid37884993, year = {2023}, author = {Schmachtenberg, T and Königs, G and Dragaqina, A and Roder, S and Müller, F and Müllenmeister, C and Schröder, D and Dopfer-Jablonka, A and Vieth, K and El-Sayed, I}, title = {"There is no one who helps you with it": experiences of people with long COVID regarding medical care, therapeutic measures, and barriers in the German healthcare system: results of a qualitative study with four focus groups.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {1160}, pmid = {37884993}, issn = {1472-6963}, mesh = {Adult ; Humans ; Focus Groups ; *COVID-19/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; Delivery of Health Care ; }, abstract = {BACKGROUND: Many people experience long-term symptoms such as fatigue, cognitive problems, or shortness of breath after an acute infection with COVID-19. This emerging syndrome, known as long COVID, is new and complex in many aspects. This study aims to collect the experiences of people with long COVID with ambulatory healthcare structures.

METHODS: Four focus groups were conducted with a total of 23 adults with long COVID in June and July 2022. These discussions were audio-recorded, subsequently transcribed, and analyzed using the qualitative content analysis of Mayring and Kuckartz.

RESULTS: Fourteen out of 19 participants who had a primary care encounter regarding their long COVID symptoms did not perceive it as helpful. Many respondents reported that their general practitioners did not take their long COVID symptoms seriously and did not refer them to specialists or made therapeutic recommendations. However, some participants reported that they were prescribed non-pharmaceutical therapies (e.g., group meetings supported by psychotherapists, occupational therapy, etc.) that improved their condition. 14 of 23 respondents perceived care barriers such as providers' lack of awareness of long COVID, poor access to specialists, a lack of specialized care (e.g., long COVID clinics), or high bureaucratic hurdles for specific healthcare services. To improve medical care, participants suggested campaigns to raise awareness of long COVID among healthcare providers and the general population, increase research and government investments regarding the development of treatment structures for long COVID, expanding existing therapeutic services, and establishing one-stop shops for integrated specialist healthcare for people with long COVID.

CONCLUSIONS: Several implications for healthcare professionals and policymakers can be derived from this study: (1) general practitioners should take the symptoms of long COVID seriously, assume a care coordinating role, make referrals, and establish contact with long COVID clinics; (2) care planners should focus on developing interprofessional evidence-based care and treatment approaches for long COVID; (3) existing care structures such as long COVID outpatient clinics should be expanded. The overarching goal must be to develop consistent guidelines for long COVID diagnosis, care, and treatment.

TRIAL REGISTRATION: The study is registered in the German register for clinical trials (DRKS00026007, first registration on 09/09/2021).}, } @article {pmid37884259, year = {2024}, author = {Palau, P and Núñez, J and Domínguez, E and Albiach, C and Marín, P and López, L}, title = {Baseline resting heart rate and responsiveness to a home-based inspiratory muscle training program in long COVID.}, journal = {Revista espanola de cardiologia (English ed.)}, volume = {77}, number = {4}, pages = {344-347}, doi = {10.1016/j.rec.2023.10.001}, pmid = {37884259}, issn = {1885-5857}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Heart Rate/physiology ; *COVID-19 ; Breathing Exercises ; Muscles ; Exercise Tolerance/physiology ; }, } @article {pmid37881468, year = {2023}, author = {Ennis, S and Heine, P and Sandhu, H and Sheehan, B and Yeung, J and McWilliams, D and Jones, C and Abraham, C and Underwood, M and Bruce, J and Seers, K and McGregor, G}, title = {Development of an online intervention for the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial.}, journal = {NIHR open research}, volume = {3}, number = {}, pages = {10}, pmid = {37881468}, issn = {2633-4402}, abstract = {BACKGROUND: Up to half of people hospitalised with COVID-19 report diverse and persistent symptoms affecting quality of life for months and sometimes years after discharge (long-COVID). We describe the development of an online group exercise and behavioural support intervention for people who continue to experience such physical and/or emotional health problems more than three months after hospital discharge.

METHODS: Intervention development was informed by the Medical Research Council framework for complex interventions. Our multidisciplinary team of academics, clinicians, and people with long-COVID, had collective expertise in the development and testing of complex interventions. We integrated a bio-psycho-social model of care drawing on rehabilitation literature for long-term health conditions and experiences from our pre-pilot study. Multiple stakeholder meetings were held to refine the intervention which was designed to be deliverable within the UK National Health Service. We adhere to TIDieR guidance for transparent and explicit reporting of telehealth interventions.

RESULTS: The final REGAIN online exercise and behavioural support intervention consisted of an initial 1:1 consultation with a trained practitioner, followed by eight online group exercise, and six group support, sessions delivered over eight weeks. Participants could also access an online library of on-demand exercise and support videos.

CONCLUSIONS: The final REGAIN intervention, combining exercise and behavioural support, is fully manualised with clear pathways to delivery and implementation. It is currently being tested in a randomised controlled trial. The intervention, developed with extensive patient and stakeholder engagement, could be incorporated into existing NHS rehabilitation programmes, should it prove to be clinically and cost-effective for people with long-COVID.

TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 11466448: Rehabilitation exercise and psychological support after COVID-19 infection: REGAIN.}, } @article {pmid37881427, year = {2023}, author = {Berentschot, JC and Drexhage, HA and Aynekulu Mersha, DG and Wijkhuijs, AJM and GeurtsvanKessel, CH and Koopmans, MPG and Voermans, JJC and Hendriks, RW and Nagtzaam, NMA and de Bie, M and Heijenbrok-Kal, MH and Bek, LM and Ribbers, GM and van den Berg-Emons, RJG and Aerts, JGJV and Dik, WA and Hellemons, ME}, title = {Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1254899}, pmid = {37881427}, issn = {1664-3224}, mesh = {Humans ; *T-Lymphocytes ; Monocytes ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Aftercare ; SARS-CoV-2 ; Patient Discharge ; Fatigue ; Cytokines ; Inflammation/complications ; }, abstract = {BACKGROUND: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).

METHODS: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge.

RESULTS: We included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8[+] TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8[+] T-lymphocyte counts.

CONCLUSION: Long COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.}, } @article {pmid37881352, year = {2023}, author = {Punj, M and Desai, A and Hashash, JG and Farraye, FA and Castillo, PR}, title = {COVID-19 breakthrough infections and sleep disorders: A population-based propensity matched analysis.}, journal = {Sleep medicine: X}, volume = {6}, number = {}, pages = {100089}, pmid = {37881352}, issn = {2590-1427}, abstract = {OBJECTIVES: Examine risks for breakthrough COVID-19 infections in vaccinated patients with selected sleep disorders.

METHODS: Real-time search and analysis using the TriNetX platform to evaluate risk of COVID-19 breakthrough infections (BTI) for patients having ICD-10 diagnoses relating to insomnia, circadian rhythm disorders, and inadequate sleep. The sleep disorder and control cohorts underwent propensity matching including factors for age, gender, race, ethnicity, and multiple co-morbid conditions.

RESULTS: Of 24,720 patients identified as having a sleep disturbance relating to insomnia, circadian rhythm disorder, or inadequate sleep, 815 (3.2 %) were found to have a developed a BTI. There was a significant increased risk of BTI noted between the sleep disorder and control cohorts (adjusted odds ratio (aOR) of 1.40, 95 % confidence interval (CI) of 1.23-1.58). Subgroup analysis showed an elevated risk for BTI receiving two doses (aOR 1.53, 95 % CI 1.24-1.89) versus three doses (aOR 1.45, 95 % CI 1.24-1.69). Patients with the sleep disturbance were not found to be at an increased risk of hospitalization, intubation, death, or composite outcome of death and intubation.

CONCLUSION: The presence of having a diagnosis of insomnia, circadian rhythm disorder, or inadequate sleep was associated with increased risk of COVID-19 breakthrough infection.}, } @article {pmid37881302, year = {2022}, author = {Haag, L and Richardson, J and Cunningham, Y and Fraser, H and Brosnahan, N and Ibbotson, T and Ormerod, J and White, C and McIntosh, E and O'Donnell, K and Sattar, N and McConnachie, A and Lean, MEJ and Blane, DN and Combet, E}, title = {The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals.}, journal = {NIHR open research}, volume = {2}, number = {}, pages = {57}, pmid = {37881302}, issn = {2633-4402}, abstract = {OBJECTVES: The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity.

METHODS: Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m [2] (>25kg/m [2] for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses).

ANTICIPATED RESULTS: The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed.

TRIAL REGISTRATION: Current Controlled Trials ISRCTN12595520.}, } @article {pmid37881207, year = {2023}, author = {Chujan, S and Nakareangrit, W and Suriyo, T and Satayavivad, J}, title = {Integrated Transcriptomics and Network Analysis of Potential Mechanisms and Health Effects of Convalescent COVID-19 Patients.}, journal = {Bioinformatics and biology insights}, volume = {17}, number = {}, pages = {11779322231206684}, pmid = {37881207}, issn = {1177-9322}, abstract = {Coronaviral disease 2019 (COVID-19) is a recent pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there are still cases of COVID-19 around the world that can develop into persistent symptoms after discharge. The constellation of symptoms, termed long COVID, persists for months and can lead to various diseases such as lung inflammation and cardiovascular disease, which may lead to considerable financial burden and possible risk to human health. Moreover, the molecular mechanisms underlying the post-pandemic syndrome of COVID-19 remain unclear. In this study, we aimed to explore the molecular mechanism, disease association, and possible health risks in convalescent COVID-19 patients. Gene expression data from a human convalescent COVID-19 data set was compared with a data set from healthy normal individuals in order to identify differentially expressed genes (DEGs). To determine biological function and potential pathway alterations, the GO and KEGG databases were used to analyze the DEGs. Disease association, tissue, and organ-specific analyses were used to identify possible health effects. A total of 250 DEGs were identified between healthy and convalescent COVID-19 subjects. The biological function alterations identified revealed cytokine interactions and increased inflammation through NF-κB1, RELA, JUN, STAT3, and SP1. Interestingly, the most significant pathways were cytokine-cytokine receptor interaction, altered lipid metabolism, and atherosclerosis that play a crucial role in convalescent COVID-19. In addition, we also found pneumonitis, dermatitis, and autoimmune diseases. Based on our study, convalescent COVID-19 is associated with inflammation in a variety of organs that could lead to autoimmune and inflammatory diseases, as well as atherosclerosis. These findings are a first step toward fully exploring the disease mechanisms in depth to understand the relationship between post-COVID-19 infection and potential health risks. This is necessary for the development of appropriate strategies for the prevention and treatment of long COVID.}, } @article {pmid37880596, year = {2023}, author = {Hill, EL and Mehta, HB and Sharma, S and Mane, K and Singh, SK and Xie, C and Cathey, E and Loomba, J and Russell, S and Spratt, H and DeWitt, PE and Ammar, N and Madlock-Brown, C and Brown, D and McMurry, JA and Chute, CG and Haendel, MA and Moffitt, R and Pfaff, ER and Bennett, TD and , and , }, title = {Risk factors associated with post-acute sequelae of SARS-CoV-2: an N3C and NIH RECOVER study.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {2103}, pmid = {37880596}, issn = {1471-2458}, support = {UM1 TR004404/TR/NCATS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UM1 TR004556/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; K01 AG070329/AG/NIA NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; K01AG070329/AG/NIA NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Middle Aged ; Female ; Male ; Humans ; Adult ; Aged ; Adolescent ; Young Adult ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Retrospective Studies ; Risk Factors ; Disease Progression ; }, abstract = {BACKGROUND: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID). The objective is to identify risk factors associated with PASC/long-COVID diagnosis.

METHODS: This was a retrospective case-control study including 31 health systems in the United States from the National COVID Cohort Collaborative (N3C). 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system and COVID index date within ± 45 days of the corresponding case's earliest COVID index date. Measurements of risk factors included demographics, comorbidities, treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC.

RESULTS: Among 8,325 individuals with PASC, the majority were > 50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30 + days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls.

CONCLUSIONS: This national study identified important risk factors for PASC diagnosis such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.}, } @article {pmid37880142, year = {2023}, author = {Zhang, Y and Li, Y}, title = {Clinical Translation of Aptamers for COVID-19.}, journal = {Journal of medicinal chemistry}, volume = {66}, number = {24}, pages = {16568-16578}, doi = {10.1021/acs.jmedchem.3c01607}, pmid = {37880142}, issn = {1520-4804}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Oligonucleotides ; }, abstract = {The COVID-19 etiologic agent, SARS-CoV-2, continues to be one of the leading causes of death on a global scale. Although efficient methods for diagnosis and treatment of COVID-19 have been developed, new methods of battling SARS-CoV-2 variants and long COVID are still urgently needed. A number of aptamers have demonstrated tremendous potential to be developed into diagnostic and therapeutic agents for COVID-19. The translation of the aptamers for clinical uses, however, has been extremely slow. Overcoming the difficulties faced by aptamers would advance this technology toward clinical use for COVID-19 and other serious disorders.}, } @article {pmid37879634, year = {2023}, author = {Pintos, I and Soriano, V}, title = {Mitochondrial damage as cause of long COVID.}, journal = {AIDS reviews}, volume = {26}, number = {3}, pages = {145-149}, doi = {10.24875/AIDSRev.M23000063}, pmid = {37879634}, issn = {1698-6997}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *HIV Infections ; DNA, Mitochondrial ; }, } @article {pmid37875801, year = {2023}, author = {Yamga, E and Soulé, A and Piché, A and Emad, A and Durand, M and Rousseau, S}, title = {Validation of ANG-1 and P-SEL as biomarkers of post-COVID-19 conditions using data from the Biobanque québécoise de la COVID-19 (BQC-19).}, journal = {Clinical proteomics}, volume = {20}, number = {1}, pages = {44}, pmid = {37875801}, issn = {1542-6416}, support = {RGPIN-2019-04460//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {The quest for understanding and managing the long-term effects of COVID-19, often referred to as Long COVID or post-COVID-19 condition (PCC), remains an active research area. Recent findings highlighted angiopoietin-1 (ANG-1) and p-selectin (P-SEL) as potential diagnostic markers, but validation is essential, given the inconsistency in COVID-19 biomarker studies. Leveraging the biobanque québécoise de la COVID-19 (BQC19) biobank, we analyzed the data of 249 participants. Both ANG-1 and P-SEL levels were significantly higher in patients with PCC participants compared with control subjects at 3 months using the Mann-Whitney U test. We managed to reproduce and validate the findings, emphasizing the importance of collaborative biobanking efforts in enhancing the reproducibility and credibility of Long COVID research outcomes.}, } @article {pmid37875300, year = {2023}, author = {Gilbert, A}, title = {There is an overlap between long covid and ME/CFS.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2462}, doi = {10.1136/bmj.p2462}, pmid = {37875300}, issn = {1756-1833}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37875298, year = {2023}, author = {Natt, A and Natt, M}, title = {Long covid clinics offer a lifeline for this isolating disease.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2458}, doi = {10.1136/bmj.p2458}, pmid = {37875298}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37874735, year = {2023}, author = {Harris, KM and Mayo Gamble, T and Yoo, MG and Spell, LA and Minor, TN and Jones, H and Lynch, D}, title = {Leveraging mHealth to Mitigate the Impact of COVID-19 in Black American Communities: Qualitative Analysis.}, journal = {JMIR human factors}, volume = {10}, number = {}, pages = {e47294}, pmid = {37874735}, issn = {2292-9495}, support = {K01 HL141676/HL/NHLBI NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; *Black or African American ; *COVID-19/epidemiology ; Educational Status ; Post-Acute COVID-19 Syndrome ; *Telemedicine ; Male ; Young Adult ; Adult ; Aged ; }, abstract = {BACKGROUND: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations.

OBJECTIVE: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, this study sought to explore COVID-19 information behavior among Black Americans. Specifically, this study examined (1) preferences for COVID-19 education via mHealth, (2) barriers and facilitators to COVID-19 education and diagnostic testing and routine care for associated cardiovascular and respiratory comorbidities in the local community, and (3) key content for inclusion in a COVID-19 mHealth app.

METHODS: This qualitative study used principles of community-based participatory research and information systems research to conduct 7 focus groups across 3 sites. Focus groups were audio recorded and transcribed for thematic analysis using an abductive approach.

RESULTS: The study sample included 54 individuals across sites with a mean age of 50.24 (SD 11.76; range 20-71) years. Participants were primarily female (n=42, 78%) and Black (n=54, 100%) with varied education levels. Over half (n=29, 54%) of the participants were employed full-time, and nearly three-fourths (n=40, 74%) had household incomes
CONCLUSIONS: Increasing transparency and building trust are 2 key strategies that may improve the impact of health information messaging in Black communities. Focusing on content over context fails in the provision of critical health information and perpetuates health inequities by reinforcing systemic and structural racism. COVID-19 messaging must consider contextual information, patient needs and preferences, and patient information-seeking and information-search behaviors to establish trust and credibility, positively impact patient health outcomes, and improve health equity.}, } @article {pmid37873397, year = {2024}, author = {Ge, Q and Zhou, S and Porras, J and Fu, P and Wang, T and Du, J and Li, K}, title = {SARS-CoV-2 neurotropism-induced anxiety/depression-like behaviors require Microglia activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.02.560570}, pmid = {37873397}, issn = {2692-8205}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of "long COVID" neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501Y MA30 , we demonstrated that intranasal inoculation of SARS2-N501Y MA30 results in viral dissemination to multiple brain regions, including the amygdala and hippocampus. Behavioral assays indicated a marked elevation in anxiety- and depression-like behaviors post infection. A comparative analysis of RNA expression profiles disclosed alterations in the post-infected brains. Additionally, we observed dendritic spine remodeling on neurons within the amygdala after infection. Infection with SARS2-N501Y MA30 was associated with microglial activation and a subsequent increase in microglia-dependent neuronal activity in the amygdala. Pharmacological inhibition of microglial activity subsequent to viral spike inoculation mitigates microglia-dependent neuronal hyperactivity. Transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating microglia-driven neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Overall, these data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.}, } @article {pmid37870325, year = {2023}, author = {Tajer, C and Martínez, MJ and Mariani, J and De Abreu, M and Antonietti, L}, title = {Post COVID-19 syndrome. Severity and evolution in 4673 health care workers.}, journal = {Medicina}, volume = {83}, number = {5}, pages = {669-682}, pmid = {37870325}, issn = {1669-9106}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Anosmia/epidemiology/etiology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Fatigue/etiology ; Health Personnel ; }, abstract = {BACKGROUND: The evolution of post COVID syndrome has been variable and we lack information on its impact on healthcare professionals, particularly in Latin America.

METHODS: We conducted a survey through a social network in health professionals on post COVID-19 syndrome cases confirmed with PCR. In a web-based questionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work.

RESULTS: 4673 health professionals from 21 countries responded, mean age of 47.8 years, 64.2% women. The initial course was asymptomatic in 9.1%, mild symptoms 36.8%, moderate symptoms without hospitalization 40.8% or with hospitalization 11.7%, and severe symptoms with respiratory assistance 1.6%. The most prevalent symptoms were fatigue (67%), insomnia (44.2%), anxiety (42.3%), myalgia (41.9%) and anosmia (41.2%). Considering only severe symptoms (grades 3-4 on a subjective index from 1 to 4), the most prevalent were slowness (36.3%), impaired concentration (33.1%), anosmia (20.4%), fatigue (19.1%), impaired memory (18.1%) and dyspnea (15.9%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the multivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7.8%, related to older age, number of symptoms and severity of the initial course.

CONCLUSION: In conclusion, in many cases the persistence of post-COVID symptoms can be prolonged and have an occupational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.}, } @article {pmid37869767, year = {2024}, author = {Vogt, H and Garner, P}, title = {'Long covid' and how medical information is causing illness: A philosophical issue affecting public health.}, journal = {Journal of evaluation in clinical practice}, volume = {30}, number = {5}, pages = {838-841}, doi = {10.1111/jep.13934}, pmid = {37869767}, issn = {1365-2753}, mesh = {Humans ; *Public Health ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37869178, year = {2023}, author = {Pérez Catalán, I and Roig Martí, C and Fabra Juana, S and Domínguez Bajo, E and Herrero Rodríguez, G and Segura Fábrega, A and Varea Villanueva, M and Folgado Escudero, S and Esteve Gimeno, MJ and Palomo de la Sota, D and Cardenal Álvarez, A and Mateu Campos, ML and Usó Blasco, J and Ramos Rincón, JM}, title = {One-year quality of life among post-hospitalization COVID-19 patients.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1236527}, pmid = {37869178}, issn = {2296-2565}, mesh = {Adolescent ; Female ; Humans ; Male ; *COVID-19/epidemiology ; *Fibromyalgia ; Hospitalization ; Obesity/epidemiology ; Quality of Life ; SARS-CoV-2 ; Adult ; }, abstract = {INTRODUCTION: The long-term effects of SARS-CoV-2 are unclear, as are the factors influencing the evolution. Objective: to assess health-related quality of life 1 year after a hospital admission due to COVID-19 and to identify factors that may influence it.

MATERIALS AND METHODS: Retrospective observational study in a tertiary hospital from March 2021 to February 2022. Inclusion criteria: ≥18 years old and admitted for SARS-CoV-2 infection. Exclusion criteria: death, not located, refusal to participate, cognitive impairment, and language barrier. Variables: demographic data, medical history, clinical and analytical outcomes during hospital admission, treatment received, and vaccination against SARS-CoV-2 following admission. Participants were interviewed by phone 1 year after admission, using the SF-36 quality of life questionnaire.

RESULTS: There were 486 included patients. The domains yielding the lowest scores were general health (median 65%, interquartile range [IQR] 45-80), vitality (median 65%, IQR 45-80), and mental health (median 73.5%, IQR 60-100). Multivariable analysis showed that female sex and fibromyalgia/fatigue had a negative influence on all domains. Obesity was associated with worse outcomes in physical functioning, physical role, bodily pain, and vitality. Other factors associated with worse scores were an older age in physical functioning and high age-adjusted Charslon comorbidity in physical functioning and general health. Age was associated with better results in emotional role and High C-reactive protein at admission on vitality.

CONCLUSION: One year after admission for COVID-19, quality of life remains affected, especially the domains of general health, vitality, and mental health. Factors associated with worse outcomes are female sex, fibromyalgia/chronic fatigue, and obesity.}, } @article {pmid37869162, year = {2023}, author = {Sanhueza, S and Vidal, MA and Hernandez, MA and Henriquez-Beltran, ME and Cabrera, C and Quiroga, R and Antilef, BE and Aguilar, KP and Castillo, DA and Llerena, FJ and Fraga Figueroa, M and Nazal, M and Castro, E and Lagos, P and Moreno, A and Lastra, JJ and Gajardo, J and Garcés, P and Riffo, B and Buchert, J and Sanhueza, R and Ormazába, V and Saldivia, P and Vargas, C and Nourdin, G and Koch, E and Zuñiga, FA and Lamperti, L and Bustos, P and Guzmán-Gutiérrez, E and Tapia, CA and Ferrada, L and Cerda, G and Woehlbier, U and Riquelme, E and Yuseff, MI and Muñoz Ramirez, BA and Lombardi, G and De Gonzalo-Calvo, D and Salomon, C and Verdugo, RA and Quiñones, LA and Colombo, A and Barría, MI and Labarca, G and Nova-Lamperti, E}, title = {Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1271863}, pmid = {37869162}, issn = {2296-858X}, abstract = {INTRODUCTION: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling.

METHODS: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection.

RESULTS: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups.

DISCUSSION: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.}, } @article {pmid37868668, year = {2023}, author = {Shah, B and Ahmad, MN and Khalid, M and Minhas, A and Ali, R and Sarfraz, Z and Sarfraz, A}, title = {Long COVID and Wavering Incidence of Pulmonary Embolism: A Systematic Review.}, journal = {Journal of community hospital internal medicine perspectives}, volume = {13}, number = {5}, pages = {23-31}, pmid = {37868668}, issn = {2000-9666}, abstract = {Pulmonary embolism (PE) is a serious medical condition that can occur as a result of venous thromboembolism (VTE). COVID-19, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), can potentially lead to PE due to the formation of blood clots in the lungs. This study aims to collate and report trends of PE in patients with long COVID (4-12 weeks since infection) and post-COVID-19 syndrome (>12 weeks since infection). The study adhered to PRISMA Statement 2020 guidelines, and a systematic search was conducted in four databases. In total, nine observational studies were included with a total patient count of 45,825,187. The incidence of PE with long COVID/post-COVID-19 syndrome was seen among 31,885 individuals out of 44,967,887 participants. The incidence rate of PE was observed as 0.07%, given that the studies included matched controls. While we cannot state with certainty that COVID-19 infection in itself leads to higher risks of PE at a later time, this study emphasizes the need for optimized care and longitudinal studies during the COVID-19 era to account for deviations from the norm.}, } @article {pmid37867587, year = {2023}, author = {Semulimi, AW and Batte, C and Iraguha, D and Okwir, PA and Atuhaire, H and Lipoto, C and Muwonge, T and Namirembe, N and Lubega, GB and Ainembabazi, P and Mukisa, J and Bongomin, F and Ssinabulya, I and Okello, E}, title = {Long COVID in Uganda: Electrographic findings among patients at risk.}, journal = {Public health challenges}, volume = {2}, number = {2}, pages = {}, pmid = {37867587}, issn = {2769-2450}, support = {D43 TW011401/TW/FIC NIH HHS/United States ; }, abstract = {BACKGROUND: COVID-19 has a significant cardiovascular involvement. Electrocardiographic (ECG) abnormalities among people at a risk of Long COVID in Uganda was investigated.

METHODS: A cross-sectional study was conducted from February to June 2022 at the post COVID - 19 clinic in Mulago National Specialized Hospital, Kampala. A standard resting ECG was performed on individuals at least 2 months following acute COVID-19, with a negative SARS-CoV-2 reverse-transcription polymerase chain reaction. Sociodemographic and clinical characteristics as well as vital signs were recorded for all study participants.

RESULTS: Of the 244 study participants, 117 (47.9%) were female. The median age of all the participants was 33.0 (interquartile range: 26.0 - 43.5) years. Twenty-five (10.2%) participants had a history of smoking while 117 (48%) had a history of alcohol intake. In total, 46 (18.9%) had abnormal ECG findings (95% Confidence Interval (CI): 14.39 - 24.29) and non-specific T-wave inversion (n = 16, 34%) was the most frequent ECG abnormality. The proportion of participants with ECG abnormalities was 48% lower among females (adjusted prevalence ratio (aPR): 0.52, 95% CI: 0.28 - 0.96, p value < 0.05) and 2-fold greater for those with a history of smoking (aPR: 2.03, 95% CI:1.096 - 3.776, p value < 0.05).

CONCLUSION: One in five Ugandans who were checked at the clinic at a risk of Long COVID showed ECG abnormalities. ECG screening is suggested to be integrated into the follow-up care of those at a risk of Long COVID.}, } @article {pmid37867460, year = {2023}, author = {Masciarella, AD and Di Gregorio, DM and Ramamoorthy, R and Hussain, H and Jayakumar, AR and Paidas, MJ}, title = {A Mouse Model of MHV-1 Virus Infection for Study of Acute and Long COVID Infection.}, journal = {Current protocols}, volume = {3}, number = {10}, pages = {e896}, pmid = {37867460}, issn = {2691-1299}, support = {R41 HD085744/HD/NICHD NIH HHS/United States ; }, mesh = {Mice ; Humans ; Animals ; *Murine hepatitis virus/genetics ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Mice, Inbred Strains ; Mice, Transgenic ; Disease Models, Animal ; }, abstract = {COVID-19, caused by SARS-CoV-2, has had a significant global impact. While vaccines and treatments have reduced severe cases and deaths, the long-term effects are not yet well understood. Current models used for research, such as non-human primates and transgenic mice, are expensive and require scarce Biosafety Level-3 (BSL-3) laboratories, thereby limiting their practicality. However, the mouse hepatitis virus 1 (MHV-1) mouse model offers a promising alternative. This surrogate model can be investigated in more widely available Biosafety Level-2 (BSL-2) laboratories. Furthermore, mice are affordable and easy to handle, and utilizing MHV-1 as a surrogate for SARS-CoV-2 eliminates the need for costly transgenic mice. Importantly, the MHV-1 model successfully recapitulates COVID-19-related clinical symptoms, weight loss, multiorgan pathological changes and failure in acute stages, irreversible neurological complications, and other long-term organ dysfunction post-infection, which are similar to available human data post-COVID-19. To assist researchers in establishing and using the MHV-1 mouse model, this protocol offers comprehensive guidance encompassing procedures for animal preparation, induction of viral infection, clinical observation, pathological changes, and tissue analysis for mechanistic studies, thereby yielding valuable insights into disease mechanisms and progression. By adopting the MHV-1 model and the provided protocols, researchers can effectively circumvent financial constraints and the limited availability of BSL-3 laboratories, thus facilitating a more accessible and cost-effective approach to investigating the underlying mechanisms of SARS-CoV-2 pathophysiology and exploring potential therapeutic interventions. © 2023 Wiley Periodicals LLC. Basic Protocol: Induction of mouse hepatitis virus 1 (MHV-1) infection in A/J mice Support Protocol 1: Histological evaluation Support Protocol 2: Liver enzyme measurement Support Protocol 3: Western blot analysis of aquaporin expression Support Protocol 4: mRNA measurement Support Protocol 5: Immunohistochemistry/immunofluorescence Support Protocol 6: Tissue water measurement.}, } @article {pmid37866679, year = {2024}, author = {Luo, D and Mei, B and Wang, P and Li, X and Chen, X and Wei, G and Kuang, F and Li, B and Su, S}, title = {Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {30}, number = {3}, pages = {328-335}, doi = {10.1016/j.cmi.2023.10.016}, pmid = {37866679}, issn = {1469-0691}, mesh = {Female ; Humans ; Male ; Anxiety/epidemiology/etiology ; *COVID-19/epidemiology/complications ; Depression/epidemiology/etiology ; Fatigue/epidemiology/etiology ; *Post-Acute COVID-19 Syndrome/complications/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Stress Disorders, Post-Traumatic/epidemiology/etiology ; }, abstract = {BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors.

OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19.

METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals.

DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023.

STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included.

PARTICIPANTS: Patients who recovered from COVID-19.

ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale.

RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index.

CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.}, } @article {pmid37866620, year = {2024}, author = {Hagiya, H and Tokumasu, K and Otsuka, Y and Sunada, N and Nakano, Y and Honda, H and Furukawa, M and Otsuka, F}, title = {Relevance of complement immunity with brain fog in patients with long COVID.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {30}, number = {3}, pages = {236-241}, doi = {10.1016/j.jiac.2023.10.016}, pmid = {37866620}, issn = {1437-7780}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Complement System Proteins/analysis ; Complement Hemolytic Activity Assay ; Mental Fatigue ; Fatigue ; }, abstract = {INTRODUCTION: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).

METHODS: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.

RESULTS: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66).

CONCLUSIONS: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.}, } @article {pmid37865841, year = {2023}, author = {Aiyegbusi, OL}, title = {COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management.}, journal = {Current opinion in neurology}, volume = {36}, number = {6}, pages = {609-614}, doi = {10.1097/WCO.0000000000001219}, pmid = {37865841}, issn = {1473-6551}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Headache/epidemiology/therapy/diagnosis ; }, abstract = {PURPOSE OF REVIEW: This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome.

RECENT FINDINGS: Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed.

SUMMARY: The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.}, } @article {pmid37864192, year = {2023}, author = {Irani, S and Chang, C and Morrison, L and Waselewski, M and Chang, T}, title = {Youth experiences with and perspectives on long covid.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {2059}, pmid = {37864192}, issn = {1471-2458}, mesh = {Humans ; Adolescent ; United States/epidemiology ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Research on the long-term effects of COVID-19 infection is ongoing, and the psychological and physical impacts of Long Covid on youth is poorly understood. To assess these impacts, we surveyed youth regarding their experiences with, and perspectives on, the long-term effects of COVID-19.

METHODS: We conducted a nationwide text message survey of youth ages 14-24 years in the United States. The survey asked four open ended questions regarding their experiences and perceptions regarding the long-term effects of COVID-19. Qualitative data was analyzed independently by three investigators using thematic analysis. Prevalence of codes were summarized using descriptive statistics.

RESULTS: Among 1150 participants, 991 responded to at least one survey question (response rate 86.1%). The vast majority of our sample had COVID-19 or knew someone who did (75%), and approximately one third (32%) of youth indicated that they knew someone who had experienced symptoms consistent with Long Covid. Many youth (50%) reported worry and concern about Long Covid even if they, or someone they knew, did not have Long Covid. Among youth who were not concerned about Long Covid, the most commonly reported reasons were having received the vaccine (29%) and not having a prior COVID-19 infection (24%).

CONCLUSIONS: Our findings suggest that among younger populations, there is significant concern regarding the long-term effects of COVID-19. Vaccination campaigns and youth-centered public health communication about Long Covid may not only reduce COVID-19 transmission, but also alleviate worries and concerns about Long Covid among youth.}, } @article {pmid37864020, year = {2024}, author = {Luchting, B and Behrends, U and Eigner, B and Stojanov, S and Warlitz, C and Haegele, M and Neuwirth, E and Mihatsch, L and Richter, HP}, title = {[Interdisciplinary multimodal pain therapy in postviral syndromes and ME/CFS : Features, pitfalls and model concept].}, journal = {Schmerz (Berlin, Germany)}, volume = {38}, number = {3}, pages = {183-189}, pmid = {37864020}, issn = {1432-2129}, mesh = {Humans ; Combined Modality Therapy ; *Intersectoral Collaboration ; *Interdisciplinary Communication ; *Pain Management/methods ; Patient Care Team ; Postpoliomyelitis Syndrome/therapy ; Psychotherapy, Group ; Cooperative Behavior ; Conversion Disorder/therapy/psychology ; }, abstract = {BACKGROUND: Multimodal pain therapy usually take place in the context of group therapy lasting several weeks and is based on a generally activating approach. Due to the specificity of stress intolerance with postexertional malaise (PEM) in patients with postviral syndromes, physical as well as psychological overload must be urgently avoided in these cases; however, these aspects can only be insufficiently considered in current medical pain therapy concepts.

METHODS: Summary of the current literature and presentation of clinical characteristics as well as presentation of a model project for a multimodal pain therapy in postviral syndromes with PEM.

MODEL CONCEPT: The presented model project describes a day clinic treatment setting for interdisciplinary multimodal pain therapy adapted to the individual resilience with minimization of the risk of strain-induced deterioration of the condition.}, } @article {pmid37859788, year = {2023}, author = {Akimoto, K and Asano, S and Satoh, Y and Yokogushi, K}, title = {Changes in respiratory, physical, and mental conditions in moderate and severe COVID-19 cases at our convalescent rehabilitation ward.}, journal = {Japanese journal of comprehensive rehabilitation science}, volume = {14}, number = {}, pages = {10-15}, pmid = {37859788}, issn = {2185-5323}, abstract = {UNLABELLED: Akimoto K, Asano S, Satoh Y, Yokogushi K. Changes in respiratory, physical, and mental conditions in moderate and severe COVID-19 cases at our convalescent rehabilitation ward. Jpn J Compr Rehabil Sci 2023; 14: 10-15.

PURPOSE: This study clarified the changes in respiratory condition, and physical and mental functions pertaining to them, of patients with the coronavirus disease 2019 ("COVID-19") who were admitted to our convalescent rehabilitation ward. It also examined the conditions remaining after the disease (long-COVID).

METHODS: We focused on 16 moderate and severe patients with COVID-19 who were transferred to our convalescent rehabilitation ward and discharged home between March and September 2021. We evaluated the patients' respiratory, physical, and mental conditions at the time of admission, four weeks after admission, and at the time of discharge.

RESULTS: We confirmed an improvement in the shortness of breath in those with respiratory conditions, and a significant improvement in the walking distance related to physical function before the time of discharge, but anxiety and depression remained.

CONCLUSION: Patients with moderate to severe COVID-19 can be discharged home after convalescent rehabilitation. Despite improved dyspnea and walking distance, the patients tend to have incomplete recovery, including physical deconditioning, mood disorders, and other long-COVID conditions at discharge.}, } @article {pmid37859501, year = {2023}, author = {Molero, P and Reina, G and Blom, JD and Martínez-González, MÁ and Reinken, A and de Kloet, ER and Molendijk, ML}, title = {COVID-19 risk, course and outcome in people with mental disorders: a systematic review and meta-analyses.}, journal = {Epidemiology and psychiatric sciences}, volume = {32}, number = {}, pages = {e61}, pmid = {37859501}, issn = {2045-7979}, mesh = {Humans ; *COVID-19/epidemiology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Bayes Theorem ; Cross-Sectional Studies ; *Mental Disorders/epidemiology ; }, abstract = {AIMS: It has been suggested that people with mental disorders have an elevated risk to acquire severe acute respiratory syndrome coronavirus 2 and to be disproportionally affected by coronavirus disease 19 (COVID-19) once infected. We aimed to analyse the COVID-19 infection rate, course and outcome, including mortality and long COVID, in people with anxiety, depressive, neurodevelopmental, schizophrenia spectrum and substance use disorders relative to control subjects without these disorders.

METHODS: This study constitutes a preregistered systematic review and random-effects frequentist and Bayesian meta-analyses. Major databases were searched up until 27 June 2023.

RESULTS: Eighty-one original articles were included reporting 304 cross-sectional and prospective effect size estimates (median n per effect-size = 114837) regarding associations of interest. Infection risk was not significantly increased for any mental disorder that we investigated relative to samples of people without these disorders. The course of COVID-19, however, is relatively severe, and long COVID and COVID-19-related hospitalization are more likely in all patient samples that we investigated. The odds of dying from COVID-19 were high in people with most types of mental disorders, except for those with anxiety and neurodevelopmental disorders relative to non-patient samples (pooled ORs range, 1.26-2.57). Bayesian analyses confirmed the findings from the frequentist approach and complemented them with estimates of the strength of evidence.

CONCLUSIONS: Once infected, people with pre-existing mental disorders are at an elevated risk for a severe COVID-19 course and outcome, including long COVID and mortality, relative to people without pre-existing mental disorders, despite an infection risk not significantly increased.}, } @article {pmid37858583, year = {2023}, author = {Müller, SA and Isaaka, L and Mumm, R and Scheidt-Nave, C and Heldt, K and Schuster, A and Abdulaziz, M and El Bcheraoui, C and Hanefeld, J and Agweyu, A}, title = {Prevalence and risk factors for long COVID and post-COVID-19 condition in Africa: a systematic review.}, journal = {The Lancet. Global health}, volume = {11}, number = {11}, pages = {e1713-e1724}, doi = {10.1016/S2214-109X(23)00384-4}, pmid = {37858583}, issn = {2214-109X}, mesh = {Child ; Humans ; Female ; Infant, Newborn ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Risk Factors ; Ghana ; }, abstract = {BACKGROUND: An improved estimation of the clinical sequelae of SARS-CoV-2 infection is crucial in African countries, where the subject has received little attention despite more than 12 million reported cases and evidence that many more people were infected. We reviewed the evidence on prevalence, associated risk factors for long COVID, and systemic or sociocultural determinants of reporting long COVID.

METHODS: We conducted a systematic review, searching PubMed, the Living OVerview of Evidence platform, and grey literature sources for publications from Dec 1, 2019, to Nov 23, 2022. We included articles published in English, French, Spanish, or Portuguese that reported on any study type in Africa with participants of any age who had symptoms for 4 weeks or more after an acute SARS-CoV-2 infection. We excluded secondary research, comments, and correspondence. Screening and data extraction were performed by two reviewers. Summary estimates were extracted, including sociodemographic factors, medical history, prevalence of persistent symptoms, and symptoms and associated factors. Results were analysed descriptively. The study was registered on the Open Science Framework platform.

FINDINGS: Our search yielded 294 articles, of which 24 peer-reviewed manuscripts were included, reporting on 9712 patients from eight African countries. Only one study exclusively recruited children, and one other study included children as part of their study population. Studies indicated moderate to low risk of bias. Prevalence of long COVID varied widely, from 2% in Ghana to 86% in Egypt. Long COVID was positively associated with female sex, older age, non-Black ethnicity, low level of education, and the severity of acute infection and underlying comorbidity. HIV and tuberculosis were not identified as risk factors. Factors influencing reporting included absence of awareness, inadequate clinical data and diagnostics, and little access to health-care services.

INTERPRETATION: In Africa, research on long COVID is scarce, particularly among children, who represent the majority of the population. However, existing studies show a substantial prevalence across settings, emphasising the importance of vaccination and other prevention strategies to avert the effects of long COVID on individual wellbeing, the increased strain on health systems, and the potential negative effects on economically vulnerable populations. At a global level, including African countries, tools for research on long COVID need to be harmonised to maximise the usefulness of the data collected.

FUNDING: None.}, } @article {pmid37858329, year = {2023}, author = {Brightling, CE and Evans, RA and Singapuri, A and Smith, N and Wain, LV and , }, title = {Long COVID research: an update from the PHOSP-COVID Scientific Summit.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {11}, pages = {e93-e94}, doi = {10.1016/S2213-2600(23)00341-7}, pmid = {37858329}, issn = {2213-2619}, support = {209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; SP/17/16/33519/BHF_/British Heart Foundation/United Kingdom ; MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; MR/S002782/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37858285, year = {2024}, author = {Berezin, L and Waseem, R and Merikanto, I and Benedict, C and Holzinger, B and De Gennaro, L and Wing, YK and Bjorvatn, B and Korman, M and Morin, CM and Espie, C and Landtblom, AM and Penzel, T and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Plazzi, G and Reis, C and Chan, RNY and Cunha, AS and Yordanova, J and Bjelajac, AK and Inoue, Y and Dauvilliers, Y and Partinen, M and Chung, F}, title = {Habitual short sleepers with pre-existing medical conditions are at higher risk of Long COVID.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {20}, number = {1}, pages = {111-119}, pmid = {37858285}, issn = {1550-9397}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Preexisting Condition Coverage ; *COVID-19/epidemiology ; Sleep ; *Sleep Wake Disorders/complications/epidemiology ; }, abstract = {STUDY OBJECTIVES: Preliminary evidence suggests that the risk of Long COVID is higher among people with pre-existing medical conditions. Based on its proven adjuvant role in immunity, habitual sleep duration may alter the risk of developing Long COVID. The objective of this study was to determine whether the odds of Long COVID are higher among those with pre-existing medical conditions, and whether the strength of this association varies by habitual sleep duration.

METHODS: Using data from 13,461 respondents from 16 countries who participated in the 2021 survey-based International COVID Sleep Study II (ICOSS II), we studied the associations between habitual sleep duration, pre-existing medical conditions, and Long COVID.

RESULTS: Of 2,508 individuals who had COVID-19, 61% reported at least 1 Long COVID symptom. Multivariable logistic regression analysis showed that the risk of having Long COVID was 1.8-fold higher for average-length sleepers (6-9 h/night) with pre-existing medical conditions compared with those without pre-existing medical conditions (adjusted odds ratio [aOR] 1.84 [1.18-2.90]; P = .008). The risk of Long COVID was 3-fold higher for short sleepers with pre-existing medical conditions (aOR 2.95 [1.04-8.4]; P = .043) and not significantly higher for long sleepers with pre-existing conditions (aOR 2.11 [0.93-4.77]; P = .073) compared with average-length sleepers without pre-existing conditions.

CONCLUSIONS: Habitual short nighttime sleep duration exacerbated the risk of Long COVID in individuals with pre-existing conditions. Restoring nighttime sleep to average duration represents a potentially modifiable behavioral factor to lower the odds of Long COVID for at-risk patients.

CITATION: Berezin L, Waseem R, Merikanto I, et al. Habitual short sleepers with pre-existing medical conditions are at higher risk of long COVID. J Clin Sleep Med. 2024;20(1):111-119.}, } @article {pmid37855873, year = {2024}, author = {Schuch, A and Walther, P and Timm, L and Steinbach, K and Haneklaus, L and Münzel, T and Prochaska, JH and Wild, PS}, title = {[Utilization of video consultation in cardiovascular lipid treatment].}, journal = {Herz}, volume = {49}, number = {3}, pages = {224-232}, pmid = {37855873}, issn = {1615-6692}, mesh = {Humans ; Male ; Female ; *COVID-19 ; *Physician-Patient Relations ; Middle Aged ; Germany ; Remote Consultation ; Cardiovascular Diseases/therapy ; Aged ; Videoconferencing ; Adult ; Telemedicine ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Video consultation is a possibility for physician-patient communication independent of the location; however, only limited information is available for the possibility of sole use since 2018.

METHODS: After the implementation of video consultation (Viomedi) in lipid consultations at the Medical University Mainz, the patients in the first quarter of 2022 were assessed depending on the possibility, suitability and readiness to participate. Included were patients under lipid management and long COVID patients. After treatment an online survey was carried out on the utilization and appraisal.

RESULTS: Of the 134 patients 29.1% were inclusively treated (3 refusals). All subjects (16 replies) reported having managed (very) well. Advantages were seen in counselling and follow-up. Problems were feared with respect to technology and possible disorders. Data protection aspects played a subordinate role. In comparison to telephone calls, a significant improvement in the physician-patient relationship (p-value = 0.00027), the quality of treatment and information (p-value both = 0.00044), the access to care (p-value = 0.0053) and the communication (p-value = 0.021) was assumed. An improvement in access to care (p-value = 0.021) and the quality of information (p-value = 0.034) was seen in comparison to personal contact. The main problems were a lack of experience, technical requirements, technical problems and unpunctuality of the practitioner. The flexibility, low effort and the pleasant consultation were all praised. All subjects wanted to use the video consultation again.

CONCLUSION: Video consultation can represent a supplement to treatment of patients under lipid management. The correct use requires exact planning and further research.}, } @article {pmid37855816, year = {2024}, author = {Thierry, AR}, title = {NETosis creates a link between diabetes and Long COVID.}, journal = {Physiological reviews}, volume = {104}, number = {2}, pages = {651-654}, doi = {10.1152/physrev.00032.2023}, pmid = {37855816}, issn = {1522-1210}, support = {DGOS 12553//SIRIC Montpellier Grant/ ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Diabetes Mellitus ; Neutrophils ; *Extracellular Traps ; }, } @article {pmid37854789, year = {2023}, author = {Pumipak, B and Jittimanee, S and Thananun, S and Mathong, K and Poungdok, J and Sinsap, M and Sueathong, T and Kongruang, O and Faungprachakorn, S and Thunyaphun, T and Insook, P and Soontornmon, K}, title = {Symptom Experience and Perceived Health Status of People With Long COVID in Thailand.}, journal = {SAGE open nursing}, volume = {9}, number = {}, pages = {23779608231206748}, pmid = {37854789}, issn = {2377-9608}, abstract = {INTRODUCTION: Despite the World Health Organization declaring COVID-19 no longer a public health emergency, reports of long COVID persist globally, raising concerns about its impact on individuals.

OBJECTIVE: This retrospective study aimed to explore the symptom experiences of individuals with long COVID-19 and examine the relationship between those experiences and perceived negative health status in Thailand.

METHODS: The study focused on individuals with moderate to severe COVID-19 infections. Between July 3, 2022 and December 1, 2022, we conducted telephone interviews with 86 individuals who tested positive for SARS-CoV-2 and received outpatient care in Bangkok. The COVID-19 Yorkshire Rehabilitation Screening was utilized to measure symptom occurrence, duration, severity, and health status on an 11-point numerical rating scale from 0 (none or excellent) to 10 (the worst). A Spearman rank correlation was used to analyze the relationships between long COVID symptoms and negative perception of health status.

RESULTS: Among the participants, 75.6% had long COVID, with a median of three symptoms lasting for a median duration of 5.6 months. Difficulties in performing daily activities were most common, reported by 50.8% of participants. The majority (80.0%) experienced itching, headache, cognition, muscle pain, continence, and sleeping problem for 6 months. Loss of taste was the most severe symptom, with a mean severity rating of 8.8. There were significant positive relations between a negative perception of health status and multiple symptoms, symptom severity, functional disability, and additional symptoms.

CONCLUSION: Individuals with moderate to severe COVID-19 infection who experienced long COVID had poorer perceived health status. To effectively manage and improve the health status of individuals with long COVID, nurses should provide follow-up care, assess not only the occurrence of symptoms but also their duration and severity, and evaluate performance outcomes.}, } @article {pmid37853144, year = {2023}, author = {McCorkell, L and Peluso, MJ}, title = {Long COVID research risks losing momentum - we need a moonshot.}, journal = {Nature}, volume = {622}, number = {7983}, pages = {457-460}, pmid = {37853144}, issn = {1476-4687}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Biomedical Research/economics/organization & administration/trends ; *Post-Acute COVID-19 Syndrome/economics/therapy ; }, } @article {pmid37852458, year = {2024}, author = {Houweling, L and Maitland-Van der Zee, AH and Holtjer, JCS and Bazdar, S and Vermeulen, RCH and Downward, GS and Bloemsma, LD}, title = {The effect of the urban exposome on COVID-19 health outcomes: A systematic review and meta-analysis.}, journal = {Environmental research}, volume = {240}, number = {Pt 2}, pages = {117351}, doi = {10.1016/j.envres.2023.117351}, pmid = {37852458}, issn = {1096-0953}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Exposome ; Pandemics ; *Air Pollutants/toxicity ; *Environmental Pollutants ; Particulate Matter/toxicity ; }, abstract = {BACKGROUND: The global severity of SARS-CoV-2 illness has been associated with various urban characteristics, including exposure to ambient air pollutants. This systematic review and meta-analysis aims to synthesize findings from ecological and non-ecological studies to investigate the impact of multiple urban-related features on a variety of COVID-19 health outcomes.

METHODS: On December 5, 2022, PubMed was searched to identify all types of observational studies that examined one or more urban exposome characteristics in relation to various COVID-19 health outcomes such as infection severity, the need for hospitalization, ICU admission, COVID pneumonia, and mortality.

RESULTS: A total of 38 non-ecological and 241 ecological studies were included in this review. Non-ecological studies highlighted the significant effects of population density, urbanization, and exposure to ambient air pollutants, particularly PM2.5. The meta-analyses revealed that a 1 μg/m[3] increase in PM2.5 was associated with a higher likelihood of COVID-19 hospitalization (pooled OR 1.08 (95% CI:1.02-1.14)) and death (pooled OR 1.06 (95% CI:1.03-1.09)). Ecological studies, in addition to confirming the findings of non-ecological studies, also indicated that higher exposure to nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), and carbon monoxide (CO), as well as lower ambient temperature, humidity, ultraviolet (UV) radiation, and less green and blue space exposure, were associated with increased COVID-19 morbidity and mortality.

CONCLUSION: This systematic review has identified several key vulnerability features related to urban areas in the context of the recent COVID-19 pandemic. The findings underscore the importance of improving policies related to urban exposures and implementing measures to protect individuals from these harmful environmental stressors.}, } @article {pmid37851732, year = {2023}, author = {Rover, MM and Trott, G and Scolari, FL and Silva, MMDD and Souza, D and Santos, RDRMD and Dagnino, APA and Mesquita Neto, J and Estivalete, GP and Kozesinski-Nakatani, AC and Marcolino, MS and Barreto, BB and Schvartzman, PR and Antonio, ACP and Robinson, CC and Falavigna, M and Biolo, A and Polanczyk, CA and Rosa, RG}, title = {Health-Related Quality of Life and Long-Term Outcomes after Mildly Symptomatic COVID-19: The Post-COVID Brazil Study 2 Protocol.}, journal = {Arquivos brasileiros de cardiologia}, volume = {120}, number = {9}, pages = {e20220835}, pmid = {37851732}, issn = {1678-4170}, mesh = {Humans ; Activities of Daily Living ; Brazil/epidemiology ; *COVID-19 ; COVID-19 Testing ; Multicenter Studies as Topic ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *Quality of Life/psychology ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The long-term effects of mild COVID-19 on physical, cognitive, and mental health are not yet well understood.

OBJECTIVE: The purpose of this paper is to describe the protocol for the ongoing "Post-COVID Brazil" study 2, which aims to evaluate the factors associated with health-related quality of life and long-term cardiovascular and non-cardiovascular outcomes one year after a mild episode of symptomatic COVID-19.

METHODS: The "Post-COVID Brazil" study 2 is a prospective multicenter study that plans to enroll 1047 patients (NCT05197647). Centralized, structured telephone interviews are conducted at 1, 3, 6, 9, and 12 months after COVID-19 diagnosis. The primary outcome is the health-related quality-of-life utility score, assessed using the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints include the EQ-5D-3L at 3, 6, and 9 months, as well as all-cause mortality, major cardiovascular events, hospitalization, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value < 0.05 will be considered statistically significant for all analyses.

RESULTS: The primary endpoint will be presented as the overall frequency of the EQ-5D-3L domains 12 months after SARS-CoV-2 infection. Main analysis will explore the association of independent variables with the study outcomes.

CONCLUSION: The "Post-COVID Brazil" study 2 aims to clarify the impact of long COVID on the quality of life and cardiovascular and non-cardiovascular outcomes of Brazilian patients who have had mild COVID-19.}, } @article {pmid37851721, year = {2023}, author = {Espíndola, O and Resende, PC and Guaraldo, L and Calvet, GA and Fuller, TL and Penetra, SLS and Santos, HFP and Pina-Costa, A and da Silva, MFB and Moraes, ICV and Medeiros, F and Whitworth, J and Smith, C and Nielsen-Saines, K and Siqueira, MM and Brasil, P}, title = {Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report.}, journal = {Memorias do Instituto Oswaldo Cruz}, volume = {118}, number = {}, pages = {e230069}, pmid = {37851721}, issn = {1678-8060}, support = {MR/V033530/1/MRC_/Medical Research Council/United Kingdom ; R01 AI140718/AI/NIAID NIH HHS/United States ; R56 AI172252/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; Aged ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brazil ; Chromosome Mapping ; }, abstract = {BACKGROUND: There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023.

OBJECTIVES: The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19.

METHODS: We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing.

FINDINGS: The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue.

MAIN CONCLUSIONS: This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.}, } @article {pmid37848295, year = {2023}, author = {Virrantaus, H and Liira, H and Posharina, T and Sulg, A and Mäntylä, T and Kanerva, M and Laakso, S and Sainio, M and Malmivaara, A and Vuokko, A and Varonen, M and Venäläinen, M and Arokoski, J}, title = {Prognosis of patients with long COVID symptoms: a protocol for a longitudinal cohort study at a primary care referred outpatient clinic in Helsinki, Finland.}, journal = {BMJ open}, volume = {13}, number = {10}, pages = {e072935}, pmid = {37848295}, issn = {2044-6055}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Longitudinal Studies ; Prospective Studies ; Finland/epidemiology ; Quality of Life ; Hand Strength ; Prognosis ; Ambulatory Care Facilities ; Primary Health Care ; Treatment Outcome ; }, abstract = {INTRODUCTION: After COVID-19, many continue to experience persistent debilitating symptoms, that is, long COVID. Its most prevalent symptoms are chest pain, difficulties with breathing, painful muscles, ageusia or anosmia, tingling extremities and general tiredness. This paper describes the protocol of the Long COVID Cohort Study to assess the prognosis and prognostic determinants of patients with long COVID by implementing patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs) and clinical examinations during a 1-year follow-up.

METHODS AND ANALYSIS: This is a prospective, single-site cohort study consisting of administering questionnaires and clinical examinations to adult patients referred to the Clinic for Long-Term Effects of COVID-19 at Helsinki University Hospital (Hospital district of Helsinki and Uusimaa). The referrals are from all healthcare units within HUS and other hospital districts during years 2021-2023. All admitted patients have had laboratory-confirmed COVID-19. The targeted study sample size is 500 participants. The questionnaires are administered at 0, 3, 6 and 12 months. The main outcome variables are the changes in self-reported functional abilities and quality of life. In addition, we will evaluate functional abilities at baseline using neurocognitive evaluation, a 6MWT and a measurement of hand grip strength. The Long COVID Cohort Study will form a quality register for the clinic and characterise the first systematic collection of PROMs, PREMs, questionnaire and clinical examinations related to long COVID in Finland. The Study belongs to a study consortium Long COVID-HORIZON-HLTH-2021-DISEASE-04 that aims to reveal the biomechanisms of long COVID.

ETHICS AND DISSEMINATION: This study has been approved by the Helsinki University Hospital research ethics committee board, ID HUS/1493/2021 on 6 March 2021. All study participants sign written informed consent for participation. The study findings will be reported for publication in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT05699512; Pre-results.}, } @article {pmid37848218, year = {2023}, author = {Mahase, E}, title = {Long covid: Researchers "extremely angry" at Boris Johnson's "bollocks" comment.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2406}, doi = {10.1136/bmj.p2406}, pmid = {37848218}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Anger ; Research Personnel ; }, } @article {pmid37848205, year = {2023}, author = {Gilbert, A}, title = {We need better care for long covid and ME/CFS.}, journal = {BMJ (Clinical research ed.)}, volume = {383}, number = {}, pages = {2372}, doi = {10.1136/bmj.p2372}, pmid = {37848205}, issn = {1756-1833}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Primary Health Care ; Qualitative Research ; }, } @article {pmid37848036, year = {2023}, author = {Wong, AC and Devason, AS and Umana, IC and Cox, TO and Dohnalová, L and Litichevskiy, L and Perla, J and Lundgren, P and Etwebi, Z and Izzo, LT and Kim, J and Tetlak, M and Descamps, HC and Park, SL and Wisser, S and McKnight, AD and Pardy, RD and Kim, J and Blank, N and Patel, S and Thum, K and Mason, S and Beltra, JC and Michieletto, MF and Ngiow, SF and Miller, BM and Liou, MJ and Madhu, B and Dmitrieva-Posocco, O and Huber, AS and Hewins, P and Petucci, C and Chu, CP and Baraniecki-Zwil, G and Giron, LB and Baxter, AE and Greenplate, AR and Kearns, C and Montone, K and Litzky, LA and Feldman, M and Henao-Mejia, J and Striepen, B and Ramage, H and Jurado, KA and Wellen, KE and O'Doherty, U and Abdel-Mohsen, M and Landay, AL and Keshavarzian, A and Henrich, TJ and Deeks, SG and Peluso, MJ and Meyer, NJ and Wherry, EJ and Abramoff, BA and Cherry, S and Thaiss, CA and Levy, M}, title = {Serotonin reduction in post-acute sequelae of viral infection.}, journal = {Cell}, volume = {186}, number = {22}, pages = {4851-4867.e20}, pmid = {37848036}, issn = {1097-4172}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; P30 AR069589/AR/NIAMS NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; R01 HL137915/HL/NHLBI NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; DP2 AG067511/AG/NIA NIH HHS/United States ; U19 AI082630/AI/NIAID NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; P01 AI108545/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; T32 AI141393/AI/NIAID NIH HHS/United States ; P01 CA210944/CA/NCI NIH HHS/United States ; R01 AA029859/AA/NIAAA NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; R01 HL137006/HL/NHLBI NIH HHS/United States ; F31 HL160065/HL/NHLBI NIH HHS/United States ; R01 DK123733/DK/NIDDK NIH HHS/United States ; R01 AI155577/AI/NIAID NIH HHS/United States ; U19 AI149680/AI/NIAID NIH HHS/United States ; T32 AI055400/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; R35 HL161196/HL/NHLBI NIH HHS/United States ; DP2 AG067492/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; COVID-19/complications ; Disease Progression ; Inflammation ; *Post-Acute COVID-19 Syndrome/blood/pathology ; *Serotonin/blood ; Virus Diseases ; }, abstract = {Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.}, } @article {pmid37847518, year = {2024}, author = {Yau, K and Tam, P and Chan, CT and Hu, Q and Qi, F and Abe, KT and Kurtesi, A and Jiang, Y and Estrada-Codecido, J and Brown, T and Liu, L and Siwakoti, A and Leis, JA and Levin, A and Oliver, MJ and Colwill, K and Gingras, AC and Hladunewich, MA}, title = {BNT162b2 versus mRNA-1273 Third Dose COVID-19 Vaccine in Patients with CKD and Maintenance Dialysis Patients.}, journal = {Clinical journal of the American Society of Nephrology : CJASN}, volume = {19}, number = {1}, pages = {85-97}, pmid = {37847518}, issn = {1555-905X}, support = {FDN 143301/CAPMC/CIHR/Canada ; 2122-HQ-000071//COVID-19 Immunity Task Force/ ; FDN 143301/CAPMC/CIHR/Canada ; 2122-HQ-000071//COVID-19 Immunity Task Force/ ; FDN 143301/CAPMC/CIHR/Canada ; }, mesh = {Humans ; *BNT162 Vaccine/administration & dosage/immunology ; *2019-nCoV Vaccine mRNA-1273/administration & dosage/immunology ; Male ; Female ; *Renal Insufficiency, Chronic/therapy/immunology ; *Renal Dialysis ; Middle Aged ; *COVID-19/prevention & control/immunology ; Aged ; *Antibodies, Viral/blood ; *COVID-19 Vaccines/administration & dosage/immunology ; *SARS-CoV-2/immunology ; Immunogenicity, Vaccine ; Spike Glycoprotein, Coronavirus/immunology ; Adult ; }, abstract = {BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations.

METHODS: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants (n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants (n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1).

RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63).

CONCLUSIONS: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period.

COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 .}, } @article {pmid37846660, year = {2023}, author = {Tomczyk, P and Tomczyk, D}, title = {Pulmonary embolism in patients in acute COVID-19, long-COVID and post-COVID syndrome.}, journal = {Przeglad epidemiologiczny}, volume = {77}, number = {2}, pages = {172-184}, doi = {10.32394/pe.77.17}, pmid = {37846660}, issn = {0033-2100}, mesh = {Humans ; *COVID-19/complications ; Anticoagulants/therapeutic use ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Venous Thromboembolism/drug therapy/epidemiology/etiology ; Poland ; *Pulmonary Embolism/etiology/epidemiology ; }, abstract = {COVID-19 is a disease caused by the SARS-CoV-2 virus, which, after entering a living organism, uses the ACE-2 protein as a receptor and several other proteins as cofactors of infection. Disease symptomatology is extensive, involving mostly predominant respiratory symptoms, as well as those of the nervous, gastrointestinal, circulatory and other systems. Incidence of COVID-19 also results in markedly different laboratory findings on the hemostatic system with the predominant feature of increased D-dimer levels. In the pathogenesis of thromboembolic complications in COVID-19, all elements of Virchow's triad are involved: endothelial damage, coagulation disorders and blood flow disorders. Coagulopathy increases with the severity of the clinical course of COVID-19. One of the causes of mortality associated with COVID-19 is pulmonary embolism. SARS-CoV-2 infection increases the risk of thromboembolic complications not only in the acute period of the disease. Also in the period of about a month after recovery, there is an increased risk of venous thrombosis and consequently, life-threatening pulmonary embolism. The classic biomarker of pulmonary embolism in the general population is D-dimers. Among imaging studies, the gold standard for diagnosing this disease is computed tomography of the pulmonary arteries (CTPA). Other useful diagnostic tests are ventilation-perfusion lung scintigraphy (VQ Scans) or echocardiography. Currently reviewed guidelines and recommendations recommend extens ive thromboprophylaxis in COVID-19 patients in both acute and chronic phases of the disease. Keywords: COVID-19, pulmonary embolism, laboratory and imaging diagnostics, thromboprophylaxis.}, } @article {pmid37846103, year = {2023}, author = {Loosen, SH and Plendl, W and Konrad, M and Tanislav, C and Luedde, T and Roderburg, C and Kostev, K}, title = {Prevalence of Upper Respiratory Tract Infections Before, During, and After the COVID-19 Pandemic in Germany: A Cross-Sectional Study of 2 167 453 Outpatients.}, journal = {Journal of primary care & community health}, volume = {14}, number = {}, pages = {21501319231204436}, pmid = {37846103}, issn = {2150-1327}, mesh = {Male ; Humans ; Child ; Female ; Aged ; Adolescent ; Young Adult ; Adult ; *COVID-19/epidemiology ; Pandemics ; Cross-Sectional Studies ; Outpatients ; Prevalence ; Post-Acute COVID-19 Syndrome ; *Respiratory Tract Infections/epidemiology ; Germany/epidemiology ; }, abstract = {BACKGROUND: Although the burden of the COVID-19 pandemic on global healthcare systems is declining, long-term sequelae such as long COVID syndrome and other disease dynamics not primarily associated with COVID-19 remain a challenge. Recent data suggest that the incidence of non-COVID upper respiratory tract infections (URTI) is increasing sharply in the post-pandemic period, but there is a lack of real-world data from Germany in this respect.

METHODS: This cross-sectional study evaluated the number of patients with a diagnosis of URTI from the Disease Analyzer database (IQVIA) between January 2019 and December 2022. The number of UTRI diagnoses per practice and the duration of sick leave per patient were compared over time.

RESULTS: A total of 1 872 935 individuals (1 403 907 patients from general practices (GP) and 469 028 patients from pediatric offices) were included, 48% of whom were female. The number of URTI patients per practice was significantly higher in 2022 than in 2019 (732 vs 464, 58%, P < .001), and this was observed for both women (56%, P < .001) and men (60%, P < .001). The post-pandemic increase in the number of URTI diagnoses correlated with age and was highest in the age group between 18 and 30 years (22%, P < .001) and lowest in older patients >70 years (3%). In pediatric patients (<18 years), the increase was highest in the age group ≤5 years (89%). Both the number of patients per practice on sick leave due to URTI (184 vs 92) and the average duration of sick leave (+2 days) increased from 2019 to 2022.

CONCLUSION: Our data suggest a dramatic increase in the incidence of URTI among all demographic subgroups in Germany between 2019 and 2022, which was associated with a tremendous impact on socioeconomic variables such as the frequency or duration of sick leave. These data could be of great importance in current pandemic management and the management of future pandemics.}, } @article {pmid37845463, year = {2023}, author = {Adingupu, DD and Soroush, A and Hansen, A and Twomey, R and Dunn, JF}, title = {Reduced Cerebrovascular Oxygenation in Individuals with Post-Acute COVID-19 Syndrome (PACS) ("long COVID").}, journal = {Advances in experimental medicine and biology}, volume = {1438}, number = {}, pages = {211-216}, pmid = {37845463}, issn = {0065-2598}, mesh = {Humans ; *Oxygen ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hypoxia ; Brain/diagnostic imaging ; }, abstract = {There is evidence that hypoxia occurs in the brain of some individuals who contracted the COVID-19 disease. Furthermore, it has been widely reported that about 13% of individuals who contracted the COVID-19 disease report persistent symptoms after the acute infection stage (>2 months post-acute infection). This is termed post-acute COVID-19 syndrome (PACS) or ("long COVID"). In this study, we aimed to determine if hypoxia measured non-invasively with frequency domain near-infrared spectroscopy (fdNIRS) occurs in asymptomatic and symptomatic individuals with post-acute COVID-19 disease. We show that 26% of our symptomatic group, measured on average 9.6 months post-acute COVID-19 disease, were hypoxic and 12% of the asymptomatic group, measured on average 2.5 months post-acute infection, were hypoxic. Our study indicates that fdNIRS measure of hypoxia in the brain may be a useful tool to identify individuals that are likely to respond to treatments targeted at reducing inflammation and improving oxygenation.}, } @article {pmid37844903, year = {2023}, author = {Cabrera-Pivaral, CE}, title = {Clinical and social importance of stool RT-PCR: a follow-up test for COVID-19 and long COVID-19.}, journal = {Cirugia y cirujanos}, volume = {91}, number = {5}, pages = {721-722}, doi = {10.24875/CIRU.22000353}, pmid = {37844903}, issn = {2444-054X}, mesh = {Humans ; *COVID-19 ; Reverse Transcriptase Polymerase Chain Reaction ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; SARS-CoV-2 ; COVID-19 Testing ; }, } @article {pmid37844358, year = {2023}, author = {Yang, L and Wu, Y and Jin, W and Mo, N and Ye, G and Su, Z and Tang, L and Wang, Y and Li, Y and Du, J}, title = {The potential role of ferroptosis in COVID-19-related cardiovascular injury.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {168}, number = {}, pages = {115637}, doi = {10.1016/j.biopha.2023.115637}, pmid = {37844358}, issn = {1950-6007}, mesh = {Humans ; Aged ; *Ferroptosis/physiology ; Reactive Oxygen Species/metabolism ; *COVID-19/complications ; *Cardiovascular Diseases/etiology ; SARS-CoV-2/metabolism ; Iron/metabolism ; *Reperfusion Injury ; }, abstract = {COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.}, } @article {pmid37844017, year = {2023}, author = {Martino, L and Morello, R and De Rose, C and Buonsenso, D}, title = {Persistent respiratory symptoms associated with post-Covid condition (Long Covid) in children: a systematic review and analysis of current gaps and future perspectives.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {10}, pages = {837-852}, doi = {10.1080/17476348.2023.2271836}, pmid = {37844017}, issn = {1747-6356}, mesh = {Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: There is increasing evidence that also children can develop Long Covid. However, there are no specific reviews providing a clear description of reported respiratory symptoms and potential diagnostics.

AREAS COVERED: We performed on PubMed a systematic search of studies conducted on children aged less than 18 years with previous SARS-CoV-2 infection complaining about persistent respiratory symptoms; the aim of our review is to characterize the incidence, pattern and duration of respiratory symptoms after the acute infection in pediatric population.

EXPERT OPINION: Children can develop persisting respiratory symptoms, as documented by several follow-up studies both including or not control groups of non-infected children. However, the methodological variabilities of the analyzed studies does not allow to provide firm conclusions about the rate, type and best diagnostics for children with persistent respiratory symptoms. Future studies should investigate on larger pediatric cohorts the role of noninvasive diagnostics and new biomarkers as well as investigating therapeutic options both during acute infection or when Long Covid has been diagnosed.}, } @article {pmid37843933, year = {2023}, author = {Carter, ES}, title = {Acupuncture for the Adjunct Treatment of Long COVID.}, journal = {American family physician}, volume = {108}, number = {4}, pages = {Online}, pmid = {37843933}, issn = {1532-0650}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; *Acupuncture Therapy ; Treatment Outcome ; }, } @article {pmid37842320, year = {2023}, author = {Sokol, Y and Silver, C and Glatt, S and Chennapragada, L and Andrusier, S and Padgett, C and Dichiara, A and Goodman, M}, title = {Long COVID coping and recovery (LCCR): Developing a novel recovery-oriented treatment for veterans with long COVID.}, journal = {Contemporary clinical trials communications}, volume = {36}, number = {}, pages = {101217}, pmid = {37842320}, issn = {2451-8654}, abstract = {BACKGROUND: Long COVID has affected 13.5% of Veterans Affairs (VA) Healthcare System users during the first pandemic year. With 700,000+ United States Veterans diagnosed with COVID-19, addressing the impact of Long COVID on this population is crucial. Since empirically-based mental health interventions for Long COVID are lacking, a vital need exists for a tailored recovery-oriented intervention for this population. This study intends to assess the feasibility and acceptability of a novel recovery-oriented intervention, Long COVID Coping and Recovery (LCCR), for Veterans with Long COVID, aiming to support symptom management and quality of life. LCCR is an adaptation of Continuous Identity Cognitive Therapy (CI-CT), a suicide recovery-oriented treatment for Veterans.

METHODS: In a two-year open-label pilot, three single-arm treatment trials will be conducted with 18 Veterans suffering from Long COVID. Each trial includes 16 weekly 60-min sessions delivered via VA Video Connect (VVC) and/or VA WebEx. Primary objectives include optimizing LCCR for Veterans with Long COVID and assessing the acceptability and feasibility of the intervention, using attendance and retention rates, drop-out statistics, and client satisfaction levels. Additionally, potential benefits of LCCR will be explored by evaluating alterations in quality of life, resilience, mental health status (anxiety, depression, suicide risk/behavior), and personal identity. The protocol has been tailored based on Veterans' needs assessment interviews and stakeholder feedback.

CONCLUSION: If the LCCR intervention proves feasible and acceptable, a manualized version will be created and a randomized controlled trial planned to examine its efficacy in the broader Veteran population.}, } @article {pmid37842301, year = {2023}, author = {Meng, QT and Song, WQ and Churilov, LP and Zhang, FM and Wang, YF}, title = {Psychophysical therapy and underlying neuroendocrine mechanisms for the rehabilitation of long COVID-19.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1120475}, pmid = {37842301}, issn = {1664-2392}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; SARS-CoV-2 ; Neurosecretory Systems ; Disease Progression ; }, abstract = {With the global epidemic and prevention of the COVID-19, long COVID-19 sequelae and its comprehensive prevention have attracted widespread attention. Long COVID-19 sequelae refer to that three months after acute COVID-19, the test of SARS-CoV-2 is negative, but some symptoms still exist, such as cough, prolonged dyspnea and fatigue, shortness of breath, palpitations and insomnia. Its pathological mechanism is related to direct viral damage, immunopathological response, endocrine and metabolism disorders. Although there are more effective methods for treating COVID-19, the treatment options available for patients with long COVID-19 remain quite limited. Psychophysical therapies, such as exercise, oxygen therapy, photobiomodulation, and meditation, have been attempted as treatment modalities for long COVID-19, which have the potential to promote recovery through immune regulation, antioxidant effects, and neuroendocrine regulation. Neuroendocrine regulation plays a significant role in repairing damage after viral infection, regulating immune homeostasis, and improving metabolic activity in patients with long COVID-19. This review uses oxytocin as an example to examine the neuroendocrine mechanisms involved in the psychophysical therapies of long COVID-19 syndrome and proposes a psychophysical strategy for the treatment of long COVID-19.}, } @article {pmid37841213, year = {2023}, author = {Yang, J and Lim, KH and Lim, KT and Woods, JT and Mohabbat, AB and Wahner-Roedler, DL and Ganesh, R and Bauer, BA}, title = {Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials.}, journal = {Therapeutic advances in chronic disease}, volume = {14}, number = {}, pages = {20406223231204727}, pmid = {37841213}, issn = {2040-6223}, support = {R21 AT001218/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking.

OBJECTIVE: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review.

DESIGN: Systematic review of randomized controlled trials (RCTs).

METHODS: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies.

RESULTS: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program.

CONCLUSION: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.}, } @article {pmid37839965, year = {2023}, author = {Del Carpio-Orantes, L and García-Méndez, S and Aguilar-Silva, A and Munguía-Sereno, ÁE}, title = {Osteomuscular and autoimmune manifestations of long COVID in Mexico.}, journal = {Reumatologia clinica}, volume = {19}, number = {9}, pages = {530-531}, doi = {10.1016/j.reumae.2023.06.001}, pmid = {37839965}, issn = {2173-5743}, } @article {pmid37838973, year = {2024}, author = {Fry, L and Logemann, A and Waldron, E and Holker, E and Porter, J and Eskridge, C and Naini, S and Basso, MR and Taylor, SE and Melnik, T and Whiteside, DM}, title = {Emotional functioning in long COVID: Comparison to post-concussion syndrome using the Personality Assessment Inventory.}, journal = {The Clinical neuropsychologist}, volume = {38}, number = {4}, pages = {963-983}, doi = {10.1080/13854046.2023.2264546}, pmid = {37838973}, issn = {1744-4144}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19/psychology/complications ; Emotions/physiology ; Neuropsychological Tests ; Personality Assessment ; Post-Acute COVID-19 Syndrome ; *Post-Concussion Syndrome/psychology/diagnosis ; }, abstract = {Objective: Recent studies on Long COVID found that patients report prominent emotional distress and significant correlations between distress and cognitive performance have been identified, raising the question of how to manage or treat these issues. To understand psychological functioning in Long COVID further, this study examined personality responses on the Personality Assessment Inventory (PAI) to compare psychological functioning in a Long COVID group with a post-concussion syndrome (PCS) group, a syndrome with a significant psychological component. Participants and methods: Participants included 201 consecutive Long COVID outpatients (Mean age = 48.87 years, mean education = 14.82, 71.6% Female, 82.6% White) and a comparison group of 102 consecutively referred PCS outpatients (Mean age = 46.08, mean education = 14.17, 63.7% Female, 88.2% White). Effect sizes and t-tests were calculated using the PAI validity, clinical, interpersonal, and treatment consideration scales as well as clinical subscales. Results: The results replicated earlier findings on the PAI in Long COVID by demonstrating that both Long COVID and PCS groups had the highest mean elevations on SOM and DEP scales but no statistically significant between group differences in mean scale elevations. Results support similarities in psychological functioning between Long COVID and PCS patients emphasizing the importance of evaluating psychological functioning in neuropsychological evaluations for these populations. Further, results suggest that psychological treatment strategies for PCS patients may be helpful for Long COVID patients, but more research is needed.}, } @article {pmid37838675, year = {2023}, author = {Sanal-Hayes, NEM and Mclaughlin, M and Hayes, LD and Mair, JL and Ormerod, J and Carless, D and Hilliard, N and Meach, R and Ingram, J and Sculthorpe, NF}, title = {A scoping review of 'Pacing' for management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): lessons learned for the long COVID pandemic.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {720}, pmid = {37838675}, issn = {1479-5876}, support = {COV/LTE/20/08/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis ; Pandemics ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise Therapy/methods ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people with ME/CFS. Whilst a definitive definition of pacing is not unanimous within the literature or healthcare providers, it typically comprises regulating activity to avoid post exertional malaise (PEM), the worsening of symptoms after an activity. Until now, characteristics of pacing, and the effects on patients' symptoms had not been systematically reviewed. This is problematic as the most common approach to pacing, pacing prescription, and the pooled efficacy of pacing was unknown. Collating evidence may help advise those suffering with similar symptoms, including long COVID, as practitioners would be better informed on methodological approaches to adopt, pacing implementation, and expected outcomes.

OBJECTIVES: In this scoping review of the literature, we aggregated type of, and outcomes of, pacing in people with ME/CFS.

ELIGIBILITY CRITERIA: Original investigations concerning pacing were considered in participants with ME/CFS.

SOURCES OF EVIDENCE: Six electronic databases (PubMed, Scholar, ScienceDirect, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched; and websites MEPedia, Action for ME, and ME Action were also searched for grey literature, to fully capture patient surveys not published in academic journals.

METHODS: A scoping review was conducted. Review selection and characterisation was performed by two independent reviewers using pretested forms.

RESULTS: Authors reviewed 177 titles and abstracts, resulting in 17 included studies: three randomised control trials (RCTs); one uncontrolled trial; one interventional case series; one retrospective observational study; two prospective observational studies; four cross-sectional observational studies; and five cross-sectional analytical studies. Studies included variable designs, durations, and outcome measures. In terms of pacing administration, studies used educational sessions and diaries for activity monitoring. Eleven studies reported benefits of pacing, four studies reported no effect, and two studies reported a detrimental effect in comparison to the control group.

CONCLUSIONS: Highly variable study designs and outcome measures, allied to poor to fair methodological quality resulted in heterogenous findings and highlights the requirement for more research examining pacing. Looking to the long COVID pandemic, our results suggest future studies should be RCTs utilising objectively quantified digitised pacing, over a longer duration of examination (i.e. longitudinal studies), using the core outcome set for patient reported outcome measures. Until these are completed, the literature base is insufficient to inform treatment practises for people with ME/CFS and long COVID.}, } @article {pmid37835106, year = {2023}, author = {Ambalavanan, R and Snead, RS and Marczika, J and Kozinsky, K and Aman, E}, title = {Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {19}, pages = {}, pmid = {37835106}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Artificial Intelligence ; Pandemics/prevention & control ; *Medical Informatics ; }, abstract = {The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. To effectively monitor the health of those affected, maintaining up-to-date health records is essential, and digital health informatics apps for surveillance play a pivotal role. In this review, we overview the existing literature on identifying and characterizing long COVID manifestations through hierarchical classification based on Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) initiative in artificial intelligence (AI) to identify long COVID. Through knowledge exploration, we present a concept map of clinical pathways for long COVID, which offers insights into the data required and explores innovative frameworks for health informatics apps for tackling the long-term effects of COVID-19. This study achieves two main objectives by comprehensively reviewing long COVID identification and characterization techniques, making it the first paper to explore incorporating long COVID as a variable risk factor within a digital health informatics application. By achieving these objectives, it provides valuable insights on long COVID's challenges and impact on public health.}, } @article {pmid37835071, year = {2023}, author = {Stein, E and Heindrich, C and Wittke, K and Kedor, C and Kim, L and Freitag, H and Krüger, A and Tölle, M and Scheibenbogen, C}, title = {Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report.}, journal = {Journal of clinical medicine}, volume = {12}, number = {19}, pages = {}, pmid = {37835071}, issn = {2077-0383}, support = {01EP2201//Federal Ministry of Education and Research/ ; }, abstract = {There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess the improvement in functional ability. Due to the urgency of finding therapies for post-COVID-Syndrome (PCS), we report here the interim results of the first ten patients, with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RCT), including sham apheresis, and for an RCT combining IA with B-cell depletion therapy. Trial registration number: NCT05629988.}, } @article {pmid37834947, year = {2023}, author = {Quaranta, VN and Portacci, A and Dragonieri, S and Locorotondo, C and Buonamico, E and Diaferia, F and Iorillo, I and Quaranta, S and Carpagnano, GE}, title = {The Predictors of Long COVID in Southeastern Italy.}, journal = {Journal of clinical medicine}, volume = {12}, number = {19}, pages = {}, pmid = {37834947}, issn = {2077-0383}, abstract = {INTRODUCTION: Long COVID is now recognized as a common consequence of the SARS-CoV-2 infection, but we are still far from fully understanding its pathogenesis and predictive factors. Many pathophysiological factors have been studied, including ethnicity. To our knowledge, the risk factors for Long COVID have not been studied in Southeastern Italy.

AIMS: The aim of this study was to evaluate the predictive factors of Long COVID in a cohort of patients from Southeastern Italy.

METHODS: We conducted a retrospective longitudinal study, enrolling inpatients and outpatients diagnosed with COVID-19 from June 2021 to March 2022. A total of 436 subjects were evaluated in an outpatient setting 12 weeks after a SARS-CoV-2 infection, recording comorbidities, symptoms, therapy, and clinical information. Univariate and multivariate binomial logistic regression analyses were performed on different risk factors to define the probability of developing Long COVID.

RESULTS: A total of 71.8% of patients (313) developed Long COVID, while the remaining 123 (28.3%) had a complete remission of symptoms 3 months after acute infection. During the acute phase of COVID-19, 68.3% of patients experienced respiratory failure and 81.4% received corticosteroid therapy. In a multivariate analysis, the female sex (SEX M ODD 0.513) and corticosteroids (ODD 2.25) were maintained as predictive values.

CONCLUSIONS: From our data and in line with other studies, the female sex emerges as a risk factor for Long COVID in the population of Southeastern Italy. Corticosteroid therapy administered in the acute phase also appears to be associated with an increased risk of Long COVID. Although indications for the prescription of corticosteroid therapy in the acute phase were indicated by the presence of pneumonia complicated by respiratory insufficiency, there was an over-prescription of corticosteroid therapy in the real life of our cohort, with 64% of patients having respiratory insufficiency and 81% having corticosteroid therapy. We hypothesize that a synergistic link between viral infection and the side effects of corticosteroid therapy may arise in selected cases.}, } @article {pmid37834897, year = {2023}, author = {Lindenmann, J and Porubsky, C and Okresa, L and Klemen, H and Mykoliuk, I and Roj, A and Koutp, A and Kink, E and Iberer, F and Kovacs, G and Krause, R and Smolle, J and Smolle-Juettner, FM}, title = {Immediate and Long-Term Effects of Hyperbaric Oxygenation in Patients with Long COVID-19 Syndrome Using SF-36 Survey and VAS Score: A Clinical Pilot Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {19}, pages = {}, pmid = {37834897}, issn = {2077-0383}, abstract = {(1) Background: Long COVID syndrome (LCS) is a heterogeneous long-standing condition following COVID-19 infection. Treatment options are limited to symptomatic measures, and no specific medication has been established. Hyperbaric oxygenation (HBO) has been found to have a positive impact on the treatment of COVID-19 infection. This study evaluates both the feasibility and outcome of supportive HBO in patients with LCS. (2) Methods: Within 17 months, 70 patients with proven LCS were prospectively included. Each patient underwent a cycle of 10 subsequent HBO treatment sessions administered for 75 min at 2.2 atmospheres. Evaluation of the patients was performed before the first and after the last HBO session and 3 months afterwards. Statistical evaluation was based on an intention-to-treat analysis using Fisher's exact test and Student's t-test for paired samples. (3) Results: In total, 59 patients (33 females, 26 males; mean age: 43.9 years; range: 23-74 years; median: 45.0) were evaluable. After HBO, a statistically significant improvement of physical functioning (p < 0.001), physical role (p = 0.01), energy (p < 0.001), emotional well-being (p < 0.001), social functioning (p < 0.001), pain (p = 0.01) and reduced limitation of activities (p < 0.001) was confirmed. (4) Conclusions: Physical functioning and both the physical and emotional role improved significantly and sustainably, suggesting HBO as a promising supportive therapeutic tool for the treatment of LCS.}, } @article {pmid37834888, year = {2023}, author = {Ogonowska-Slodownik, A and Labecka, MK and Maciejewska-Skrendo, A and McNamara, RJ and Kaczmarczyk, K and Starczewski, M and Gajewski, J and Morgulec-Adamowicz, N}, title = {Effect of Water-Based vs. Land-Based Exercise Intervention (postCOVIDkids) on Exercise Capacity, Fatigue, and Quality of Life in Children with Post COVID-19 Condition: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {12}, number = {19}, pages = {}, pmid = {37834888}, issn = {2077-0383}, support = {BPN/GIN/2021/1/00071//Polish National Agency for Academic Exchange/ ; }, abstract = {Evidence suggests that COVID-19 can cause lasting health consequences called post-COVID-19 condition. We conducted a three-group, randomized controlled trial for children aged 10-12 years with post COVID-19 condition. Participants were randomized to AQUA, LAND, or CONTROL groups. The AQUA and LAND training sessions were conducted twice a week for eight weeks. The primary outcomes were exercise capacity, measured using the modified Balke treadmill protocol, and fatigue, measured using the Cumulative Fatigue Symptoms Questionnaire (CFSQ). The secondary outcome was health-related quality of life (HRQoL), measured with the Pediatric Quality of Life Inventory (PedsQL) for children and parents. A total of 74 of the 86 children completed the intervention and attended the post-intervention assessment. The absolute maximal oxygen uptake (VO2max) values increased after both AQUA (p = 0.001) and LAND (p = 0.004) interventions. No significant differences were found in the degree of total fatigue and individual fatigue symptoms. A significant improvement was found in the PedsQL reported by the parents in the LAND group. In conclusion, the applied eight-week water-based and land-based exercise training programs improved exercise capacity in children aged 10-12 years old with post COVID-19 condition. The parents of the children in the training groups also noted an improvement in HRQoL.}, } @article {pmid37834324, year = {2023}, author = {Georgieva, E and Ananiev, J and Yovchev, Y and Arabadzhiev, G and Abrashev, H and Abrasheva, D and Atanasov, V and Kostandieva, R and Mitev, M and Petkova-Parlapanska, K and Karamalakova, Y and Koleva-Korkelia, I and Tsoneva, V and Nikolova, G}, title = {COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834324}, issn = {1422-0067}, support = {Project № BG-RRP-2.004-0006-C02//Bulgarian Ministry of Education and Science (MES) in the frames of Bulgarian National Recovery and Resilience Plan, Component "Innovative Bulgaria" the Project № BG-RRP-2.004-0006-C02 "Development of research and innovation at Trakia University in service/ ; Young Scientists and Postdoctoral Students-2//Bulgarian Ministry of Education and Science under the National Program/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Inflammation ; Oxidative Stress ; Free Radicals ; }, abstract = {SARS-CoV-2 infection, discovered and isolated in Wuhan City, Hubei Province, China, causes acute atypical respiratory symptoms and has led to profound changes in our lives. COVID-19 is characterized by a wide range of complications, which include pulmonary embolism, thromboembolism and arterial clot formation, arrhythmias, cardiomyopathy, multiorgan failure, and more. The disease has caused a worldwide pandemic, and despite various measures such as social distancing, various preventive strategies, and therapeutic approaches, and the creation of vaccines, the novel coronavirus infection (COVID-19) still hides many mysteries for the scientific community. Oxidative stress has been suggested to play an essential role in the pathogenesis of COVID-19, and determining free radical levels in patients with coronavirus infection may provide an insight into disease severity. The generation of abnormal levels of oxidants under a COVID-19-induced cytokine storm causes the irreversible oxidation of a wide range of macromolecules and subsequent damage to cells, tissues, and organs. Clinical studies have shown that oxidative stress initiates endothelial damage, which increases the risk of complications in COVID-19 and post-COVID-19 or long-COVID-19 cases. This review describes the role of oxidative stress and free radicals in the mediation of COVID-19-induced mitochondrial and endothelial dysfunction.}, } @article {pmid37834270, year = {2023}, author = {Moreno-Corona, NC and López-Ortega, O and Pérez-Martínez, CA and Martínez-Castillo, M and De Jesús-González, LA and León-Reyes, G and León-Juárez, M}, title = {Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834270}, issn = {1422-0067}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Dysbiosis/complications ; *COVID-19/complications ; SARS-CoV-2 ; *Microbiota ; }, abstract = {Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.}, } @article {pmid37833640, year = {2023}, author = {Varisco, B and Bai, F and De Benedittis, S and Tavelli, A and Cozzi-Lepri, A and Sala, M and Miraglia, FG and Santoro, MM and Ceccherini-Silberstein, F and Shimoni, Y and Ravid, S and Kozlovski, T and König, F and Pfeifer, N and Shamsara, E and Parczewski, M and Monforte, AD and Incardona, F and Mommo, C and Marchetti, G}, title = {EuCARE-POSTCOVID Study: a multicentre cohort study on long-term post-COVID-19 manifestations.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {684}, pmid = {37833640}, issn = {1471-2334}, mesh = {Female ; Humans ; Cohort Studies ; *COVID-19/epidemiology ; Fatigue/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Quality of Life ; Retrospective Studies ; *SARS-CoV-2 ; Male ; }, abstract = {BACKGROUND: Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10-20% of patients and reaching 50-60% in certain cohorts, while the associated risk factors remain poorly understood.

METHODS: This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period. Patients will be followed up at the post-COVID-19 clinic of each centre at 2-3, 6-9, and 12-15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders.

DISCUSSION: This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs.

TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov under the identifier NCT05531773.}, } @article {pmid37832998, year = {2023}, author = {Voss, JG and Pinto, MD and Burton, CW}, title = {How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.}, journal = {The Nursing clinics of North America}, volume = {58}, number = {4}, pages = {541-568}, doi = {10.1016/j.cnur.2023.07.004}, pmid = {37832998}, issn = {1558-1357}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Social Determinants of Health ; Disease Progression ; }, abstract = {The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.}, } @article {pmid37832757, year = {2023}, author = {Mclaughlin, M and Sanal-Hayes, NEM and Hayes, LD and Berry, EC and Sculthorpe, NF}, title = {People with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Exhibit Similarly Impaired Vascular Function.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2023.09.013}, pmid = {37832757}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {BACKGROUND: This study aimed to compare flow-mediated dilation values between individuals with long COVID, individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes.

METHODS: A case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analyzed using 1-way analysis of variance for between-group comparisons.

RESULTS: Results revealed significantly impaired endothelial function in both long COVID and ME/CFS groups compared with healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared with pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs 11.30 ± 4.44%, respectively, both P < .05). Notably, there was no difference in flow-mediated dilation between long COVID and ME/CFS groups (P = .949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs long COVID: 1.36 ± 0.51 years, P < .0001).

CONCLUSION: The study demonstrates that both long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses. The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.}, } @article {pmid37832276, year = {2023}, author = {Sirotiak, Z and Thomas, EBK and Brellenthin, AG}, title = {Stress, anxiety, and depression severity among individuals with no history, previous history, or current history of long COVID.}, journal = {Journal of psychosomatic research}, volume = {175}, number = {}, pages = {111519}, doi = {10.1016/j.jpsychores.2023.111519}, pmid = {37832276}, issn = {1879-1360}, mesh = {Adult ; Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Pandemics ; Depression/diagnosis/epidemiology/psychology ; Cross-Sectional Studies ; Anxiety/epidemiology ; Stress, Psychological/epidemiology/psychology ; }, abstract = {OBJECTIVE: Long COVID has been associated with psychological symptoms, yet it is unknown if the symptom burden of individuals with current and previous long COVID differ. This pre-registered cross-sectional study assessed stress, anxiety, and depression severity among individuals with no history, previous history, or current long COVID symptoms.

METHODS: Adults (N = 2872) in the United States participated in an online survey detailing experiences related to the COVID-19 pandemic. Included participants reported ≥1 COVID-19 infection, and self-reported long COVID symptoms (past and present) were assessed. A multivariable linear regression evaluated the association of long COVID status and stress, anxiety, and depression severity. Post-hoc contrasts were performed to probe significant differences among no, previous, and current long COVID symptom groups.

RESULTS: Of 2872 participants with history of COVID-19 infection, 2310 reported no history of, 183 reported previous history of, and 379 reported current long COVID symptoms. Participants were an average 41.3 years of age, with most identifying as female (51.7%), White (87.7%), and non-Hispanic or Latino (84.1%). Individuals with current and previous history of long COVID reported greater stress, anxiety, and depression compared to the no history group (all ps < 0.05; current vs. no history Cohen's ds = 0.71-0.93; previous vs. no history ds = 0.30-0.66) after adjusting for demographic and lifestyle factors.

CONCLUSIONS: Both current and previous long COVID may be associated with psychological symptoms.}, } @article {pmid37832076, year = {2023}, author = {Getsuwan, S and Boonsathorn, S and Chaisavaneeyakorn, S and Butsriphum, N and Tanpowpong, P and Lertudomphonwanit, C and Treepongkaruna, S}, title = {Clinical manifestations and outcomes of coronavirus disease 2019 among pediatric liver transplant recipients in the delta and omicron variant pandemic: A retrospective study.}, journal = {Medicine}, volume = {102}, number = {41}, pages = {e35537}, pmid = {37832076}, issn = {1536-5964}, mesh = {Humans ; Child ; Retrospective Studies ; BNT162 Vaccine ; *COVID-19/epidemiology ; *Liver Transplantation ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fever ; Transplant Recipients ; }, abstract = {To determine the clinical manifestations and outcomes of the coronavirus disease 2019 (COVID-19) in children who underwent liver transplantation (LT). A retrospective study was conducted at a transplant center in Thailand to include LT recipients aged < 18 years who had been infected with COVID-19. Out of a total of 54 children, there were 31 probable cases (57.4%) diagnosed using an antigen test kit and 23 confirmed cases (42.6%) diagnosed using polymerase chain reaction (14 children) or severe acute respiratory syndrome coronavirus 2 antigen (9 children). Approximately half of the children (25, 46.3%) received the BNT162b2 vaccine before the infection, with 3 and 2 doses in 5 and 18 children, respectively. While some had COVID-19 during the delta pandemic, most (46 children, 85.2%) were infected during the omicron pandemic, of which manifestations included fever (67.4%), cough (50%), and rhinorrhea (47.8%), and symptoms lasted approximately 3 days. None had severe diseases. All patients with mild-to-moderate disease were advised to continue the same immunosuppressive therapy as before the infection. Compared to unvaccinated children or children with one dose of the vaccine, fever was less common in those who received ≥ 2 doses (OR: 0.08; 95%CI: 0.01-0.57, adjusted for age and immunosuppressive types). Favipiravir was prescribed in most patients (90.7%). Only a few children had long COVID-19 or abnormal liver function tests lasting > 1 month (4 children, 7.4%, both). Pediatric LT recipients with COVID-19 during the delta and omicron variant pandemic reported mild symptoms despite undergoing immunosuppressive therapy.}, } @article {pmid37831706, year = {2023}, author = {Kennelly, CE and Nguyen, ATP and Sheikhan, NY and Strudwick, G and Ski, CF and Thompson, DR and Bartram, M and Soklaridis, S and Rossell, SL and Castle, D and Hawke, LD}, title = {The lived experience of long COVID: A qualitative study of mental health, quality of life, and coping.}, journal = {PloS one}, volume = {18}, number = {10}, pages = {e0292630}, pmid = {37831706}, issn = {1932-6203}, support = {WI1-179893//CIHR/Canada ; }, mesh = {Adult ; Humans ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; Adaptation, Psychological ; Qualitative Research ; }, abstract = {The majority of people who contract COVID-19 experience a short period of symptomatic infection. However, symptoms persist for months or years following initial exposure to the virus in some cases. This has been described as long COVID. Little is known about the lived experience of this condition, as it has only recently emerged. This study aimed to explore the experiences of mental health, quality of life, and coping among people living with long COVID. A sample of 47 adults with lived experience participated in web-based focus groups. Separate focus groups were held for 24 individuals with pre-existing mental health conditions and 23 individuals without pre-existing mental health conditions. Data were analyzed using a codebook thematic analysis approach. Five themes were identified as integral to the long COVID experience: The Emotional Landscape of Long COVID, New Limits to Daily Functioning, Grief and Loss of Former Identity, Long COVID-related Stigmatization, and Learning to Cope with Persisting Symptoms. These findings illustrate the immense impact of long COVID on mental health and quality of life. Minimal differences were found between those with and those without pre-existing mental health conditions, as both groups were substantially impacted by the condition. Attention to the perspectives of people with lived experience of long COVID is necessary to inform future directions for research and clinical practice.}, } @article {pmid37830667, year = {2023}, author = {Romero-Rodriguez, E and Perula-de Torres, LA and Monserrat-Villatoro, J and Gonzalez-Lama, J and Carmona-Casado, AB and Ranchal-Sanchez, A}, title = {Sociodemographic and Clinical Profile of Long COVID-19 Patients, and Its Correlation with Medical Leave: A Comprehensive Descriptive and Multicenter Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {19}, pages = {}, pmid = {37830667}, issn = {2227-9032}, support = {AP-0184-2021-C2-F2//Fundación Progreso y Salud/ ; IMIBIC 2022 Open Access Publications//Instituto Maimónides de Investigación Biomédica de Córdoba/ ; }, abstract = {The persistent condition of COVID-19 is characterized by a wide range of symptoms that have had a significant impact on both the health status and occupational life of the population. In this observational and multicenter study, the relationship between the sociodemographic and clinical profile of Spanish patients diagnosed with long COVID, and the work-related disability resulting from this pathology was analyzed. The analysis included 689 responses. A descriptive analysis of the variables recorded was performed, together with a bivariate analysis to determine associations between work-related disability and variables such as gender, age, health status, disabling symptoms or comorbidities. The results obtained highlight fatigue and lack of concentration (brain fog) as the most incapacitating symptoms among patients diagnosed with long COVID. Multivariate analysis revealed that time since diagnosis (OR: 0.57, CI95%: 0.36-0.89, p: 0.013), concomitant renal insufficiency (OR: 4.04, CI95%: 1.42-11.4, p: 0.008), and symptoms like fatigue (OR: 0.56, CI95%: 0.33-0.99) and tremors (OR: 2.0, CI95%: 1.06-3.69, p: 0.029), were associated with work-related disability. These findings highlight the need to improve the health and work-related management of this condition in the healthcare system. Besides risk factor control, it is suggested to pay special attention to determining the appropriate timing of medical leave work reintegration, along with coordination between primary care and occupational health services to ensure the gradual and tailored return of patients with long COVID to the workforce.}, } @article {pmid37830367, year = {2023}, author = {Durstenfeld, MS and Peluso, MJ and Spinelli, MA and Li, D and Hoh, R and Chenna, A and Yee, B and Winslow, J and Petropoulos, C and Gandhi, M and Henrich, TJ and Aras, MA and Long, CS and Deeks, SG and Hsue, PY}, title = {Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID With Exercise Capacity and Chronotropic Incompetence Among People With HIV.}, journal = {Journal of the American Heart Association}, volume = {12}, number = {20}, pages = {e030896}, pmid = {37830367}, issn = {2047-9980}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; L30 HL159695/HL/NHLBI NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; Middle Aged ; Male ; Post-Acute COVID-19 Syndrome ; Exercise Tolerance/physiology ; Cross-Sectional Studies ; *COVID-19 ; SARS-CoV-2 ; *HIV Infections/complications/diagnosis/epidemiology ; }, abstract = {Background Postacute sequelae of COVID-19 (PASC) and HIV are both associated with reduced exercise capacity, but whether SARS-CoV-2 or PASC are associated with exercise capacity among people with HIV (PWH) is unknown. We hypothesized that PWH with PASC would have reduced exercise capacity from chronotropic incompetence. Methods and Results We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH with and without prior SARS-CoV-2 infection and people without HIV with prior SARS-CoV-2 infection (controls). We evaluated associations of HIV, SARS-CoV-2, and PASC with exercise capacity (peak oxygen consumption) and chronotropy (adjusted heart rate reserve). We included 83 participants (median age, 54 years; 35% women; 37 PWH): 23 out of 37 (62%) PWH and all 46 controls had prior SARS-CoV-2 infection, and 11 out of 23 (48%) PWH and 28 out of 46 (61%) without HIV had PASC. Peak oxygen consumption was reduced among PWH versus controls (80% predicted versus 99%, P=0.005), a difference of 5.5 mL/kg per minute (95% CI, 2.7-8.2; P<0.001). Chronotropic incompetence was more prevalent among PWH (38% versus 11%, P=0.002), with lower adjusted heart rate reserve (60% versus 83%, P<0.0001) versus controls. Among PWH, SARS-CoV-2 coinfection and PASC were not associated with exercise capacity. Chronotropic incompetence was more common among PWH with PASC: 7 out of 11 (64%) with PASC versus 7 out of 26 (27%) without PASC (P=0.04). Conclusions Exercise capacity and chronotropy are lower among PWH compared with individuals with SARS-CoV-2 infection without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a common underrecognized mechanism of exercise intolerance among PWH, especially those with cardiopulmonary PASC.}, } @article {pmid37829821, year = {2023}, author = {Clemente, L and La Rocca, M and Quaranta, N and Iannuzzi, L and Vecchio, E and Brunetti, A and Gentile, E and Dibattista, M and Lobasso, S and Bevilacqua, V and Stramaglia, S and de Tommaso, M}, title = {Prefrontal dysfunction in post-COVID-19 hyposmia: an EEG/fNIRS study.}, journal = {Frontiers in human neuroscience}, volume = {17}, number = {}, pages = {1240831}, pmid = {37829821}, issn = {1662-5161}, abstract = {INTRODUCTION: Subtle cognitive dysfunction and mental fatigue are frequent after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, characterizing the so-called long COVID-19 syndrome. This study aimed to correlate cognitive, neurophysiological, and olfactory function in a group of subjects who experienced acute SARS-CoV-2 infection with persistent hyposmia at least 12 weeks before the observation.

METHODS: For each participant (32 post-COVID-19 patients and 16 controls), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) data were acquired using an integrated EEG-fNIRS system during the execution of a P300 odd-ball task and a Stroop test. The Sniffin' Sticks test was conducted to assess subjects' olfactory performance. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were also administered.

RESULTS: The post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender (X[2] = 0, p = 1) or age between the two groups (age 44.81 ± 13.9 vs. 36.62 ± 11.4, p = 0.058). We identified a lower concentration of oxyhemoglobin (p < 0.05) at the prefrontal cortical level in post-COVID-19 subjects during the execution of the Stroop task, as well as a reduction in the amplitude of the P3a response. Moreover, we found that post-COVID-19 subjects performed worst at the MoCA screening test (p = 0.001), Sniffin's Sticks test (p < 0.001), and Stroop task response latency test (p < 0.001).

CONCLUSIONS: This study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection. These deficits, although subtle, could have long-term implications for quality of life and cognitive wellbeing. It is essential to continue monitoring and evaluating these patients to better understand the extent and duration of cognitive impairments associated with long COVID-19.}, } @article {pmid37828990, year = {2023}, author = {Shafqat, A and Omer, MH and Albalkhi, I and Alabdul Razzak, G and Abdulkader, H and Abdul Rab, S and Sabbah, BN and Alkattan, K and Yaqinuddin, A}, title = {Neutrophil extracellular traps and long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1254310}, pmid = {37828990}, issn = {1664-3224}, mesh = {Humans ; *Extracellular Traps ; *COVID-19/metabolism ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Pulmonary Fibrosis/etiology/metabolism ; Inflammation/metabolism ; }, abstract = {Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.}, } @article {pmid37828951, year = {2023}, author = {Vicens-Zygmunt, V and Pérez-Rubio, G and Chavez-Galan, L and Buendia-Roldan, I and Falfán-Valencia, R}, title = {Editorial: Translational research in severe COVID-19 and long-term symptoms post-COVID-19.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1261211}, pmid = {37828951}, issn = {2296-858X}, } @article {pmid37824353, year = {2023}, author = {Tran, TK and Nguyen Truong, S and Tran Thanh, L and Le Hoang Gia, N and Pham Trung, H and Tran Dinh, B}, title = {Post-COVID condition: a survey of patients recovered from COVID-19 in Central Vietnam.}, journal = {Journal of infection in developing countries}, volume = {17}, number = {9}, pages = {1213-1220}, doi = {10.3855/jidc.18029}, pmid = {37824353}, issn = {1972-2680}, mesh = {Humans ; *COVID-19/epidemiology ; Cough/epidemiology ; Cross-Sectional Studies ; Vietnam/epidemiology ; Post-Acute COVID-19 Syndrome ; Fatigue/epidemiology ; }, abstract = {INTRODUCTION: Evidence on post-COVID-19 conditions is emerging. This study aims to assess post-COVID conditions and related factors in COVID-19 patients in Central Vietnam.

METHODOLOGY: A descriptive cross-sectional study was performed on people who have recovered from COVID-19 at least 2 weeks prior to the online survey. Participants were interviewed face-to-face after 6 and 9 months from the first survey.

RESULTS: 53 patients (21.2%) were confirmed to have persistent symptoms, of which, 100% and 94.3% reported prolonged fatigue and full-body weakness respectively. Loss of appetite was reported by 90.6%, while persistent cough, insomnia, and trouble sleeping were reported by 86.3% of patients. Headaches and dyspnea were reported by 69.5% and 56.8% respectively, while other symptoms had lower rates. The prevalence of post-COVID condition showed a statistically significant relationship with the time of infection, duration of illness, treatment place, use of herbal medicine, adherence to the 5K message from Vietnam's Ministry of Health, and daily saltwater mouthwash (p < 0.05). However, the use of medicine and supplements was not related to the post-COVID condition (p > 0.05). After 6 months, 125 participants were interviewed face-to-face, and only 15 people (12.0%) reported having post-COVID symptoms, mainly prolonged fatigue (33.3%) and persistent cough (26.7%). After 9 months, these 15 patients no longer had symptoms related to the post- COVID-19 condition.

CONCLUSIONS: The post-COVID condition can persist for several weeks or months, but will mostly be in remission after 6 months, and completely resolve after 9 months from the onset of the infection.}, } @article {pmid37822557, year = {2023}, author = {Allan-Blitz, LT and Hu, H and Klausner, JD}, title = {What Long COVID Prevention Strategies Suggest About Its Pathophysiology.}, journal = {Open forum infectious diseases}, volume = {10}, number = {10}, pages = {ofad466}, pmid = {37822557}, issn = {2328-8957}, } @article {pmid37822090, year = {2024}, author = {Nara, N and Shimizu, M and Yamamoto, M and Nakamizo, T and Hayakawa, A and Johkura, K}, title = {Prolonged platelet hyperactivity after COVID-19 infection.}, journal = {British journal of haematology}, volume = {204}, number = {2}, pages = {492-496}, doi = {10.1111/bjh.19125}, pmid = {37822090}, issn = {1365-2141}, support = {//Yokohama Foundation for the Advancement of Medical Science/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Blood Platelets ; Follow-Up Studies ; }, abstract = {Platelet hyperactivity often occurs in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear how long platelet hyperactivity lasts after the acute phase, owing to a lack of follow-up studies. To elucidate the course of platelet hyperactivity, we serially measured platelet activity in patients with COVID-19 up to 40 days after hospital admission using an easily assessable haematology analyser that semi-quantitates platelet clumps on a scattergram. Our results showed that platelet hyperactivity persisted for at least 40 days even after acute inflammation subsided in most patients with COVID-19, regardless of disease severity. Persistent platelet hyperactivity may contribute to thromboembolic complications in post-COVID-19 patients.}, } @article {pmid37821939, year = {2023}, author = {Hawke, LD and Nguyen, ATP and Sheikhan, NY and Strudwick, G and Rossell, SL and Soklaridis, S and Kloiber, S and Shields, R and Ski, CF and Thompson, DR and Castle, D}, title = {Swept under the carpet: a qualitative study of patient perspectives on Long COVID, treatments, services, and mental health.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {1088}, pmid = {37821939}, issn = {1472-6963}, mesh = {Humans ; Adult ; Middle Aged ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/therapy ; Floors and Floorcoverings ; SARS-CoV-2 ; Qualitative Research ; }, abstract = {BACKGROUND: A constellation of often disabling long-term physical symptoms enduring after an acute SARS-COV-2 infection is commonly referred to as Long COVID. Since Long COVID is a new clinical entity, research is required to clarify treatment needs and experiences of individuals affected. This qualitative descriptive study aimed to provide insight into Long COVID treatment and service experiences and preferences of individuals experiencing Long COVID and the intersections with mental health.

METHODS: The study was conducted out of a tertiary care mental health hospital, with online recruitment from the community across Canada. A total of 47 individuals (average age = 44.9) participated in one of 11 focus groups between June and December 2022. Five focus groups were conducted with participants who had pre-existing mental health concerns prior to contracting SARS-CoV-2, and six were with people with Long COVID but without pre-existing mental health concerns. A semi-structured interview guide asked about service experiences and service preferences, including mental health and well-being services. Discussions were recorded, transcribed, and analyzed using codebook thematic analysis.

RESULTS: When accessing services for Long COVID, patients experienced: (1) systemic barriers to accessing care, and (2) challenges navigating the unknowns of Long COVID, leading to (3) negative impacts on patient emotional well-being and recovery. Participants called for improvements in Long COVID care, with a focus on: (1) developing Long COVID-specific knowledge and services, (2) enhancing support for financial well-being, daily living, and building a Long COVID community, and (3) improving awareness and the public representation of Long COVID.

CONCLUSIONS: Substantial treatment barriers generate considerable burden for individuals living with Long COVID. There is a pressing need to improve treatment, social supports, and the social representation of Long COVID to create integrated, accessible, responsive, and ongoing support systems.}, } @article {pmid37820685, year = {2023}, author = {Richter, D and Theodoridou, A}, title = {[A virus and its consequences: COVID-19 and Long Covid - A hybrid disease model].}, journal = {Psychiatrische Praxis}, volume = {50}, number = {7}, pages = {341-343}, doi = {10.1055/a-2168-4553}, pmid = {37820685}, issn = {1439-0876}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Germany ; }, } @article {pmid37819953, year = {2023}, author = {}, title = {The Long Haul of Long Covid.}, journal = {The New England journal of medicine}, volume = {389}, number = {15}, pages = {e29}, doi = {10.1056/NEJMp2309483}, pmid = {37819953}, issn = {1533-4406}, mesh = {Humans ; COVID-19 ; *Post-Acute COVID-19 Syndrome ; }, } @article {pmid37817031, year = {2024}, author = {Megha, KB and Reshma, S and Amir, S and Krishnan, MJA and Shimona, A and Alka, R and Mohanan, PV}, title = {Comprehensive Risk Assessment of Infection Induced by SARS-CoV-2.}, journal = {Molecular neurobiology}, volume = {61}, number = {12}, pages = {9851-9872}, pmid = {37817031}, issn = {1559-1182}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *SARS-CoV-2 ; Risk Assessment ; Host-Pathogen Interactions ; Pandemics ; }, abstract = {The pandemic COVID-19 (coronavirus disease 2019) is caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which devastated the global economy and healthcare system. The infection caused an unforeseen rise in COVID-19 patients and increased the mortality rate globally. This study gives an overall idea about host-pathogen interaction, immune responses to COVID-19, recovery status of infection, targeted organs and complications associated, and comparison of post-infection immunity in convalescent subjects and non-infected individuals. The emergence of the variants and episodes of COVID-19 infections made the situation worsen. The timely introduction of vaccines and precautionary measures helped control the infection's severity. Later, the population that recovered from COVID-19 grew significantly. However, understanding the impact of healthcare issues resulting after infection is paramount for improving an individual's health status. It is now recognised that COVID-19 infection affects multiple organs and exhibits a broad range of clinical manifestations. So, post COVID-19 infection creates a high risk in individuals with already prevailing health complications. The identification of post-COVID-19-related health issues and their appropriate management is of greater importance to improving patient's quality of life. The persistence, sequelae and other medical complications that normally last from weeks to months after the recovery of the initial infection are involved with COVID-19. A multi-disciplinary approach is necessary for the development of preventive measures, techniques for rehabilitation and strategies for clinical management when it comes to long-term care.}, } @article {pmid37816952, year = {2023}, author = {Flemming, A}, title = {The distinctive immune features of long COVID.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {11}, pages = {703}, pmid = {37816952}, issn = {1474-1741}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37816478, year = {2024}, author = {Wright, TJ and Pyles, RB and Sheffield-Moore, M and Deer, RR and Randolph, KM and McGovern, KA and Danesi, CP and Gilkison, CR and Ward, WW and Vargas, JA and Armstrong, PA and Lindsay, SE and Zaidan, MF and Seashore, J and Wexler, TL and Masel, BE and Urban, RJ}, title = {Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study.}, journal = {Molecular and cellular endocrinology}, volume = {579}, number = {}, pages = {112071}, doi = {10.1016/j.mce.2023.112071}, pmid = {37816478}, issn = {1872-8057}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Pilot Projects ; Quality of Life ; Case-Control Studies ; Disease Progression ; Fatigue ; Growth Hormone ; }, abstract = {OBJECTIVE: To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology.

DESIGN: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function.

RESULTS: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion.

CONCLUSIONS: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www.

CLINICALTRIALS: gov; NCT04860869).}, } @article {pmid37816256, year = {2023}, author = {Reinfeld, S and Sala, M}, title = {Exploring Therapeutic Approaches for Long COVID Neuropsychiatric Sequelae: Current Understanding and Potential Strategies.}, journal = {The primary care companion for CNS disorders}, volume = {25}, number = {5}, pages = {}, doi = {10.4088/PCC.23br03592}, pmid = {37816256}, issn = {2155-7780}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid37816180, year = {2023}, author = {Riepl, M and Kaiser, J}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 5: Associated Conditions, Prophylaxis, and Effective Treatment.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {5}, pages = {368-380}, pmid = {37816180}, issn = {1092-4221}, mesh = {Humans ; *COVID-19/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; }, abstract = {The effects of infection with the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus- disease-2019 (COVID-19) it engenders continue to demonstrate that worldwide, the detection, prediction, and control of novel-pathogen pandemics remain largely unattained achievements. Key to successfully meeting those goals is a thorough understanding of the mechanisms of evolving causative agents and effective prophylaxis against them. In this article, we review common conditions that afflict people with COVID-19 or long COVID, examine the effectiveness of vaccines designed to prevent infection with SARS-CoV-2 and mitigate its sequelae, and provide formulations for 2 compounded preparations that can assist recovery from acute and chronic conditions caused by that virus when manufactured drugs are unavailable in required dosages or dosage forms or cannot be tolerated by the patient.}, } @article {pmid37815903, year = {2023}, author = {Wei, ZD and Liang, K and Shetty, AK}, title = {Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments.}, journal = {Aging and disease}, volume = {14}, number = {6}, pages = {1958-1966}, pmid = {37815903}, issn = {2152-5250}, support = {R01 AG075440/AG/NIA NIH HHS/United States ; R01 NS106907/NS/NINDS NIH HHS/United States ; RF1 AG074256/AG/NIA NIH HHS/United States ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a recent worldwide coronavirus disease-2019 (COVID-19) pandemic. SARS-CoV-2 primarily causes an acute respiratory infection but can progress into significant neurological complications in some. Moreover, patients with severe acute COVID-19 could develop debilitating long-term sequela. Long-COVID is characterized by chronic symptoms that persist months after the initial infection. Common complaints are fatigue, myalgias, depression, anxiety, and "brain fog," or cognitive and memory impairments. A recent study demonstrated that a mild COVID-19 respiratory infection could generate elevated proinflammatory cytokines and chemokines in the cerebral spinal fluid. This commentary discusses findings from this study, demonstrating that even a mild respiratory SARS-CoV-2 infection can cause considerable neuroinflammation with microglial and macrophage reactivity. Such changes could also be gleaned by measuring chemokines and cytokines in the circulating blood. Moreover, neuroinflammation caused by mild SARS-CoV-2 infection can also impair hippocampal neurogenesis, deplete oligodendrocytes, and decrease myelinated axons. All these changes likely contribute to cognitive deficits in long-COVID syndrome. Therefore, strategies capable of restraining neuroinflammation, maintaining better hippocampal neurogenesis, and preserving oligodendrocyte lineage differentiation and maturation may prevent or reduce the incidence of long-COVID after SARS-CoV-2 respiratory infection.}, } @article {pmid37814744, year = {2023}, author = {Karyakarte, RP and Das, R and Rajmane, MV and Dudhate, S and Agarasen, J and Pillai, P and Chandankhede, PM and Labhshetwar, RS and Gadiyal, Y and Kulkarni, PP and Nizarudeen, S and Mukade, S and Joshi, S}, title = {The Burden and Characteristics of Post-COVID-19 Conditions Among Laboratory-Confirmed Delta and Omicron COVID-19 Cases: A Preliminary Study From Maharashtra, India.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44888}, pmid = {37814744}, issn = {2168-8184}, abstract = {BACKGROUND: Post-COVID-19 conditions (PCC) have emerged as a significant global health concern due to their potential impact on patients' quality of life and healthcare resources. The present study aims to understand the burden and characteristics of PCC in Maharashtra, India, and compares its prevalence among cases infected with Delta and Omicron variants.

MATERIAL AND METHODS: A retrospective observational study included 617 laboratory-confirmed Delta and Omicron variant cases. These cases were telephonically followed up to document persistent COVID-19 symptoms using a questionnaire based on the Post-COVID-19 Clinical Form from the Global COVID-19 Clinical Platform of the World Health Organization (WHO), and the results were analyzed.

RESULTS: Out of 617 laboratory-confirmed COVID-19 cases, 82.97% and 17.03% were Omicron and Delta cases, respectively. The mean follow-up period for Delta and Omicron cases was 78.05 and 21.56 weeks, respectively. A total of 40 (6.48%) cases reported persistent symptoms at follow-up, with a higher prevalence among those infected with the Delta variant (12.38%) compared to the Omicron variant (5.27%). The most common long COVID symptoms reported were malaise (25%), dyspnea (20%), post-exertional fatigue (17.5%), joint pain (15%), and frequent episodes of cough and cold (15%). Additionally, 1.94% of participants developed a new medical condition following COVID-19 infection, most commonly hypertension (25%), lung fibrosis (16.67%), and asthma (8.33%). Factors such as more than five acute symptoms, a moderate to severe disease, the need for hospitalization, and hospitalization for more than five days were significantly associated with PCC.

CONCLUSION: Long COVID results in extended disability and illness. The varying impacts of different COVID-19 variants highlight the complex nature of post-COVID-19 complications. Our findings highlight the need for strategic planning of healthcare resources to ensure optimal response and preparedness to manage the burden of PCC.}, } @article {pmid37814605, year = {2023}, author = {Lim, JK and Njei, B}, title = {Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.}, journal = {Hepatic medicine : evidence and research}, volume = {15}, number = {}, pages = {151-164}, pmid = {37814605}, issn = {1179-1535}, abstract = {The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.}, } @article {pmid37814234, year = {2023}, author = {Nair, P and Nair, CV and Kulirankal, KG and Corley, EM and Edathadathil, F and Gutjahr, G and Moni, M and Sathyapalan, DT}, title = {Characterization and predictive risk scoring of long COVID in a south indian cohort after breakthrough COVID infection; a prospective single centre study.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {670}, pmid = {37814234}, issn = {1471-2334}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; COVID-19 Testing ; *Diabetes Mellitus, Type 2 ; Pandemics ; Prospective Studies ; Quality of Life ; *Asthma ; Breakthrough Infections ; *Hypertension ; }, abstract = {BACKGROUND: With the World Health Organization (WHO) declaring an end to the COVID-19 pandemic, the focus has shifted to understanding and managing long-term post-infectious complications. "Long COVID," characterized by persistent or new onset symptoms extending beyond the initial phase of infection, is one such complication. This study aims to describe the incidence, clinical features and risk profile of long COVID among individuals in a South Indian cohort who experienced post-ChAdOx1 n-Cov-2 vaccine breakthrough infections.

METHODS: A single-centre hospital-based prospective observational study was conducted from October to December 2021. The study population comprised adult patients (> 18 years) with a confirmed COVID-19 diagnosis who had received at least a single dose of vaccination. Data was collected using a specially tailored questionnaire at week 2, week 6, and week 12 post-negative COVID-19 test. A propensity score based predictive scoring system was developed to assess the risk of long COVID.

RESULTS: Among the 414 patients followed up in the study, 164 (39.6%) reported long COVID symptoms persisting beyond 6 week's post-infection. The presence of long COVID was significantly higher among patients above 65 years of age, and those with comorbidities such as Type II Diabetes Mellitus, hypertension, dyslipidemia, coronary artery disease, asthma, and cancer. Using backwards selection, a reduced model was developed, identifying age (OR 1.053, 95% CI 0.097-1.07, p < 0.001), hypertension (OR 2.59, 95% CI 1.46-4.59, p = 0.001), and bronchial asthma (OR 3.7176, 95% CI 1.24-11.12, p = 0.018) as significant predictors of long COVID incidence. A significant positive correlation was observed between the symptomatic burden and the number of individual comorbidities.

CONCLUSIONS: The significant presence of long COVID at 12 weeks among non-hospitalised patients underscores the importance of post-recovery follow-up to assess for the presence of long COVID. The predictive risk score proposed in this study may help identify individuals at risk of developing long COVID. Further research is needed to understand the impact of long COVID on patients' quality of life and the potential role of tailored rehabilitation programs in improving patient outcomes.}, } @article {pmid37811836, year = {2023}, author = {Muyayalo, KP and Gong, GS and Kiyonga Aimeé, K and Liao, AH}, title = {Impaired immune response against SARS-CoV-2 infection is the major factor indirectly altering reproductive function in COVID-19 patients: a narrative review.}, journal = {Human fertility (Cambridge, England)}, volume = {26}, number = {4}, pages = {778-796}, doi = {10.1080/14647273.2023.2262757}, pmid = {37811836}, issn = {1742-8149}, mesh = {Humans ; Female ; Male ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/physiology ; Inflammation ; Immunity ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.}, } @article {pmid37811367, year = {2023}, author = {Dvořáková, T and Měrková, R and Bušková, J}, title = {Sleep disorders after COVID-19 in Czech population: Post-lockdown national online survey.}, journal = {Sleep medicine: X}, volume = {6}, number = {}, pages = {100087}, pmid = {37811367}, issn = {2590-1427}, abstract = {OBJECTIVE: This study aimed to determine the frequency, type, and correlates of a broad spectrum of sleep disorders in adults with COVID-19 up to 32 months after infection.

METHODS: We conducted a national online survey (Jun 2021-Dec 2022), gathering information on COVID-19 diagnosis, acute disease course, and the subsequent development of sleep disorders from 1507 respondents (mean age 44.5 ± 13.1 years, 64.1% women).

RESULTS: 81.3% (1223) reported at least one sleep difficulty that either worsened or first appeared with COVID-19. Females reported a higher number of symptoms (2.03 ± 1.44 versus 1.72 ± 1.43 in men, p < 0.0001). Most common were insomnia symptoms (59.4%), followed by night sweats (38.4%), hypersomnolence (33.3%), vivid dreams or nightmares (26.4%), restless leg syndrome (RLS) (22.8%), and sleep-related breathing disorders (11.1%). All symptoms were associated with a more severe acute disease. A mild decreasing trend in the persistence of sleep symptoms with a longer latency since infection was observed, with 66.7% reporting at least half of their symptoms present at 3-5 months after acute infection, compared to 64.9% at 6-8 months, and 62.4% at 9-11 months (p = 0.0427). However, among those after 12 or more months, over half of the symptoms persisted in 69.5%. The frequency of vivid dreams and nightmares increased in association with COVID-19 in 32.9% (p < 0.001). 9.4% (141) reported new-onset or increased parasomnic manifestations after the infection.

CONCLUSIONS: Our research shows that sleep disturbances are a common and persistent manifestation of COVID-19 that affects a large proportion of the population and deserves careful monitoring.}, } @article {pmid37811128, year = {2023}, author = {Luo, S and Zheng, Z and Bird, SR and Plebanski, M and Figueiredo, B and Jessup, R and Stelmach, W and Robinson, JA and Xenos, S and Olasoji, M and Wan, DWL and Sheahan, J and Itsiopoulos, C}, title = {An Overview of Long COVID Support Services in Australia and International Clinical Guidelines, With a Proposed Care Model in a Global Context.}, journal = {Public health reviews}, volume = {44}, number = {}, pages = {1606084}, pmid = {37811128}, issn = {0301-0422}, abstract = {Objective: To identify gaps among Australian Long COVID support services and guidelines alongside recommendations for future health programs. Methods: Electronic databases and seven government health websites were searched for Long COVID-specific programs or clinics available in Australia as well as international and Australian management guidelines. Results: Five Long COVID specific guidelines and sixteen Australian services were reviewed. The majority of Australian services provided multidisciplinary rehabilitation programs with service models generally consistent with international and national guidelines. Most services included physiotherapists and psychologists. While early investigation at week 4 after contraction of COVID-19 is recommended by the Australian, UK and US guidelines, this was not consistently implemented. Conclusion: Besides Long COVID clinics, future solutions should focus on early identification that can be delivered by General Practitioners and all credentialed allied health professions. Study findings highlight an urgent need for innovative care models that address individual patient needs at an affordable cost. We propose a model that focuses on patient-led self-care with further enhancement via multi-disciplinary care tools.}, } @article {pmid37811042, year = {2023}, author = {Khan, SA and Ashkar, R and Kumari, S and Khenhrani, RR and Ullah, S and Rajpar, R and Arshad, H and Haque, JA and Abbas, K and Khan, J and Poudel, B and Bhandari, S and Ahmed, M and Dars, JA}, title = {Long COVID syndrome: psychological and sexual dysfunction among survivors of COVID-19 infection.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {10}, pages = {4788-4793}, pmid = {37811042}, issn = {2049-0801}, abstract = {BACKGROUND: To explore the neuropsychiatric symptoms, sleep disturbances, and sexual dysfunction in patients with long COVID syndrome, which can help in building better follow-up strategies for coronavirus disease 2019 (COVID-19) survivors.

MATERIAL AND METHODS: A cross-sectional research was undertaken at the premises of a psychiatry unit at a tertiary care unit in Karachi, Pakistan, between August 2022 and April 2023. All individuals aged 18 years or older, who had a history of contracting COVID-19 infection in the last 12 months presented to the department of Psychiatry with neuropsychiatric symptoms were recruited. Using a predefined questionnaire, data was collected from the participants. A linear logistic regression was used to find the impact of age, sex, hospitalization, and duration of home isolation on the likelihood of persistent neuropsychiatric symptoms or sexual dysfunction.

RESULTS: A total of 457 patients were included. It was found that individuals were less likely to experience neuropsychiatric symptoms as age increased (OR=0.968, 95% CI: 0.949-0.986, P=0.001). Females were 4.8 times more likely to experience neuropsychiatric symptoms than males, and the association was extremely significant (OR=4.851, 95% CI: 3.085-7.626, P<0.0001). An increase in age raised the odds of having sleep disturbances among the survivors by 2.7 times (OR=2.672, 95% CI: 2.654-2.684, P<0.0001). The odds of having sleep disturbances were three times more likely in female participants as compared to male participants (OR=3.00, 95% CI: 1.771-5.094, P<0.0001).

CONCLUSION: The majority of the COVID-19 survivors are presenting with persistent neuropsychiatric and sexual symptoms in our setting. Therefore, it is necessary to maintain proper follow-up with the survivors of COVID-19 and counsel the patients to inform the family physician if these symptoms persist for longer than a month. Increasing such practices of regular follow-ups with COVID-19 survivors can help in detecting early neuropsychiatric and sexual changes.}, } @article {pmid37809592, year = {2023}, author = {Turner, S and Laubscher, GJ and Khan, MA and Kell, DB and Pretorius, E}, title = {Accelerating discovery: A novel flow cytometric method for detecting fibrin(ogen) amyloid microclots using long COVID as a model.}, journal = {Heliyon}, volume = {9}, number = {9}, pages = {e19605}, pmid = {37809592}, issn = {2405-8440}, abstract = {Long COVID has become a significant global health and economic burden, yet there are currently no established methods or diagnostic tools to identify which patients might benefit from specific treatments. One of the major pathophysiological factors contributing to Long COVID is the presence of hypercoagulability; this results in insoluble amyloid microclots that are resistant to fibrinolysis. Our previous research using fluorescence microscopy has demonstrated a significant amyloid microclot load in Long COVID patients. However, this approach lacked the elements of statistical robustness, objectivity, and rapid throughput. In the current study, we have used imaging flow cytometry for the first time to show a significantly increased concentration and size of these microclots. We identified notable variations in size and fluorescence between microclots in Long COVID and those of controls even using a 20× objective. By combining cell imaging and the high-event-rate and full-sample analysis nature of a conventional flow cytometer, imaging flow cytometry can eliminate erroneous results and increase accuracy in gating and analysis beyond what pure quantitative measurements from conventional flow cytometry can provide. Although imaging flow cytometry was used in our study, our results suggest that the signals indicating the presence of microclots should be easily detectable using a conventional flow cytometer. Flow cytometry is a more widely available technique than fluorescence microscopy and has been used in pathology laboratories for decades, rendering it a potentially more suitable and accessible method for detecting microclots in individuals suffering from Long COVID or conditions with similar pathology, such as myalgic encephalomyelitis.}, } @article {pmid37809325, year = {2023}, author = {Toussirot, E and Maglio, M and Fini, M and Salamanna, F}, title = {Editorial: Impact and consequences of COVID-19 on the musculoskeletal system.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1288778}, pmid = {37809325}, issn = {2296-858X}, } @article {pmid37809081, year = {2023}, author = {Limoges, MA and Quenum, AJI and Chowdhury, MMH and Rexhepi, F and Namvarpour, M and Akbari, SA and Rioux-Perreault, C and Nandi, M and Lucier, JF and Lemaire-Paquette, S and Premkumar, L and Durocher, Y and Cantin, A and Lévesque, S and Dionne, IJ and Menendez, A and Ilangumaran, S and Allard-Chamard, H and Piché, A and Ramanathan, S}, title = {SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1223936}, pmid = {37809081}, issn = {1664-3224}, support = {GA4-177773//CIHR/Canada ; }, mesh = {Humans ; Female ; Male ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antibody Formation ; Pandemics ; Immunoglobulin G ; }, abstract = {BACKGROUND: Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.

METHODS: The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.

RESULTS: The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD[-]CD27[-]) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.

CONCLUSIONS: The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.}, } @article {pmid37808803, year = {2023}, author = {Razzaghi, H and Forrest, CB and Hirabayashi, K and Wu, Q and Allen, A and Rao, S and Chen, Y and Bunnell, HT and Chrischilles, EA and Cowell, LG and Cummins, MR and Hanauer, DA and Higginbotham, M and Horne, BD and Horowitz, CR and Jhaveri, R and Kim, S and Mishkin, A and Muszynski, JA and Naggie, S and Pajor, NM and Paranjape, A and Schwenk, HT and Sills, MR and Tedla, YG and Williams, DA and Bailey, C}, title = {Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.27.23296100}, pmid = {37808803}, abstract = {OBJECTIVE: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years.

METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination.

RESULTS: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months.

DISCUSSION: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data.

ARTICLE SUMMARY: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months.

Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID.

WHAT THIS STUDY ADDS: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months.

Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

AUTHORSHIP STATEMENT: Authorship has been determined according to ICMJE recommendations.}, } @article {pmid37806865, year = {2024}, author = {Ceban, F and Kulzhabayeva, D and Rodrigues, NB and Di Vincenzo, JD and Gill, H and Subramaniapillai, M and Lui, LMW and Cao, B and Mansur, RB and Ho, RC and Burke, MJ and Rhee, TG and Rosenblat, JD and McIntyre, RS}, title = {Corrigendum to "COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis" [Brain Behav. Immun. 111 (2023) 211-229].}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {758}, doi = {10.1016/j.bbi.2023.09.020}, pmid = {37806865}, issn = {1090-2139}, } @article {pmid37805875, year = {2023}, author = {De Vitis, R and Passiatore, M and Cilli, V and Apicella, M and Taccardo, G}, title = {SARS-COV-2 INFECTION AND INVOLVEMENT OF PERIPHERAL NERVOUS SYSTEM: A CASE SERIES OF CARPAL TUNNEL SYNDROME AGGRAVATION OR NEW ONSET WITH COVID-19 DISEASE AND A REVIEW OF LITERATURE.}, journal = {Georgian medical news}, volume = {}, number = {340-341}, pages = {61-66}, pmid = {37805875}, issn = {1512-0112}, mesh = {Humans ; *Carpal Tunnel Syndrome/diagnosis/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Median Nerve ; *Median Neuropathy/complications ; }, abstract = {COVID-19 may be asymptomatic or have a typical presentation with fever, cough, anosmia, lymphocytopenia. In some cases, it occurs with a "chimeric" presentation, with more subtle and ambiguous symptoms which may be initially misdiagnosed and are referred to in long covid condition. A possible central and peripheral nervous system involvement has been recognized. We present our experience and review the literature about association between carpal tunnel syndrome (CTS) and hand's arthritis presenting a case series of patients who firmly state that their condition of CTS arised or got worse during a typical presentation of COVID-19. The outbreak of COVID-19 has resulted in significant global healthcare implications. While the respiratory manifestations of COVID-19 have been widely studied, there is emerging evidence suggesting potential associations between COVID-19 and various other health conditions. This review of the literature aims to investigate the potential relationship between COVID-19 and the development or exacerbation of CTS. By synthesizing the available literature on this topic, we aim to provide a comprehensive overview of the current knowledge and enhance our understanding of the potential implications of COVID-19 on CTS. Case series: In this article we report 13 cases of typical presentations of COVID-19 with fever, myalgia, and respiratory system involvement, with a simultaneous aggravation of the median nerve pre-existing neuralgia and some cases that developed a median nerve neuralgia during COVID-19, which came to the attention of the hand surgeon. Some cases had stable symptomatic CTS and were on waiting list for surgical carpal tunnel release, some cases were previously asymptomatic and developed a median nerve neuralgia during COVID-19. All patients referred to a rapid worsening of acral paraesthesia and neuralgic pain of the same quality of CTS and in the median nerve topography. Some patients developed typical COVID-19 symptoms and died; the others were surgically treated. CTS could be an atypical presentations of COVID-19 or a condition of long-covid disease and clinical and epidemiological significance needs to be fully studied. We presented cases of worsening of the median nerve neuralgia which presented among other symptoms of COVID infection. We conclude a causal relation may exist and needs to be further investigated.}, } @article {pmid37804756, year = {2023}, author = {Pallanti, S and Di Ponzio, M and Gavazzi, G and Gasic, G and Besteher, B and Heller, C and Kikinis, R and Makris, N and Kikinis, Z}, title = {From 'mental fog' to post-acute COVID-19 syndrome's executive function alteration: Implications for clinical approach.}, journal = {Journal of psychiatric research}, volume = {167}, number = {}, pages = {10-15}, doi = {10.1016/j.jpsychires.2023.09.017}, pmid = {37804756}, issn = {1879-1379}, mesh = {Humans ; *Executive Function/physiology ; Male ; Female ; *COVID-19/blood/complications ; *Post-Acute COVID-19 Syndrome ; Adult ; Middle Aged ; Young Adult ; Aged ; Adolescent ; Aged, 80 and over ; Interleukin-6/blood ; Neuropsychological Tests ; }, abstract = {A common symptom of the neuropsychiatric Post-Acute COVID-19 syndrome (neuro-PACS) is the so called 'brain fog'. Patients describe the brain fog as problems with attention, memory and mental fatigue. Brain fog is experienced by 9-55% of people for months after having contracted SARS-CoV-2 virus. Several theories have been proposed to explain PACS's brain fog, including a neuroinflammatory hypothesis, but the hypothesis remains to be proven. Here, we examined inflammatory and immunological blood profile in a cohort of patients with PACS to investigate the association between executive functions and blood inflammatory markers. Executive function was assessed by the Trail Making Test (TMT) Part A and Part B, as well as the Barkley Deficits in Executive Functioning Scale (BDEFS), in 71 patients (36 men), average age of 40 years (range: 15-82, SD: 15.7). Impairment in executive functioning (BDEFS scores and TMT B scores) correlated with increased levels of Interleukin-6 (IL-6), fibrinogen and ferritin. Moreover, elevated levels of Il-6, fibrinogen, ferritin, tumor necrosis factor-alpha and C-reactive protein have been observed in PACS. These findings demonstrate that PACS is characterized by the presence of an immuno-inflammatory process, which is associated with diminished executive functioning. Here, we argue in favour of a shift from the non-descriptive definition of 'mental fog' to a characterization of a subtype of PACS, associated with alteration in executive functioning. Implication for clinical settings and prevention are discussed.}, } @article {pmid37804660, year = {2023}, author = {Bonilla, H and Tian, L and Marconi, VC and Shafer, R and McComsey, GA and Miglis, M and Yang, P and Bonilla, A and Eggert, L and Geng, LN}, title = {Low-dose naltrexone use for the management of post-acute sequelae of COVID-19.}, journal = {International immunopharmacology}, volume = {124}, number = {Pt B}, pages = {110966}, pmid = {37804660}, issn = {1878-1705}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Naltrexone/therapeutic use ; SARS-CoV-2 ; Disease Progression ; }, abstract = {The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.}, } @article {pmid37804653, year = {2023}, author = {Pereira, VIC and de Brito Junior, LC and Falcão, LFM and da Costa Vasconcelos, PF and Quaresma, JAS and Berg, AVVD and Paixão, APS and Ferreira, RIS and Diks, IBC}, title = {Monocytes subpopulations pattern in the acute respiratory syndrome coronavirus 2 virus infection and after long COVID-19.}, journal = {International immunopharmacology}, volume = {124}, number = {Pt B}, pages = {110994}, doi = {10.1016/j.intimp.2023.110994}, pmid = {37804653}, issn = {1878-1705}, mesh = {Humans ; Monocytes ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Zika Virus ; *Zika Virus Infection/diagnosis ; *Chikungunya virus ; Receptors, IgG ; Lipopolysaccharide Receptors ; }, abstract = {INTRODUTION AND OBJECTIVE: The present study sought to characterize the pattern of monocyte subpopulations in patients during the course of the infections caused by SARS-CoV-2 virus or who presented long COVID-19 syndrome compared to monocytes from patients with zika virus (Zika) or chikungunya virus (CHIKV).

CASUISTRY: Study with 89 peripheral blood samples from patients, who underwent hemogram and serology (IgG and IgM) for detection of Zika (Control Group 1, n = 18) or CHIKV (Control Group 2, n = 9), and from patients who underwent hemogram and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 at the acute phase of the disease (Group 3, n = 19); and of patients who presented long COVID-19 syndrome (Group 4, n = 43). The monocyte and subpopulations counts were performed by flow cytometry.

RESULTS: No significant difference was observed in the total number of monocytes between the groups. The classical (CD14[++]CD16[-]) and intermediate (CD14[+]CD16[+]) monocytes counts were increased in patients with acute infection or with long COVID-19 syndrome. The monocytes subpopulations counts were lower in patients with infection Zika or CHIKV.

CONCLUSION: Increase in the monocyte subpopulations in patients with acute infection or with long COVID-19 syndrome may be an important finding of differentiated from the infection Zika or CHIKV.}, } @article {pmid37803311, year = {2023}, author = {Hoerger, M and Kim, S and Mossman, B and Alonzi, S and Xu, K and Coward, JC and Whalen, K and Nauman, E and Miller, J and De La Cerda, T and Peyser, T and Dunn, A and Zapolin, D and Rivera, D and Murugesan, N and Baker, CN}, title = {Cultivating community-based participatory research (CBPR) to respond to the COVID-19 pandemic: an illustrative example of partnership and topic prioritization in the food services industry.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1939}, pmid = {37803311}, issn = {1471-2458}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Pandemics/prevention & control ; Community-Based Participatory Research ; Post-Acute COVID-19 Syndrome ; Community Health Services ; *Substance-Related Disorders ; }, abstract = {BACKGROUND: As an illustrative example of COVID-19 pandemic community-based participatory research (CBPR), we describe a community-academic partnership to prioritize future research most important to people experiencing high occupational exposure to COVID-19 - food service workers. Food service workers face key challenges surrounding (1) health and safety precautions, (2) stress and mental health, and (3) the long-term pandemic impact.

METHOD: Using CBPR methodologies, academic scientists partnered with community stakeholders to develop the research aims, methods, and measures, and interpret and disseminate results. We conducted a survey, three focus groups, and a rapid qualitative assessment to understand the three areas of concern and prioritize future research.

RESULTS: The survey showed that food service employers mainly supported basic droplet protections (soap, hand sanitizer, gloves), rather than comprehensive airborne protections (high-quality masks, air quality monitoring, air cleaning). Food service workers faced challenging decisions surrounding isolation, quarantine, testing, masking, vaccines, and in-home transmission, described anxiety, depression, and substance use as top mental health concerns, and described long-term physical and financial concerns. Focus groups provided qualitative examples of concerns experienced by food service workers and narrowed topic prioritization. The rapid qualitative assessment identified key needs and opportunities, with help reducing in-home COVID-19 transmission identified as a top priority. COVID-19 mitigation scientists offered recommendations for reducing in-home transmission.

CONCLUSIONS: The COVID-19 pandemic has forced food service workers to experience complex decisions about health and safety, stress and mental health concerns, and longer-term concerns. Challenging health decisions included attempting to avoid an airborne infectious illness when employers were mainly only concerned with droplet precautions and trying to decide protocols for testing and isolation without clear guidance, free tests, or paid sick leave. Key mental health concerns were anxiety, depression, and substance use. Longer-term challenges included Long COVID, lack of mental healthcare access, and financial instability. Food service workers suggest the need for more research aimed at reducing in-home COVID-19 transmission and supporting long-term mental health, physical health, and financial concerns. This research provides an illustrative example of how to cultivate community-based partnerships to respond to immediate and critical issues affecting populations most burdened by public health crises.}, } @article {pmid37801299, year = {2023}, author = {El-Maradny, YA and Rubio-Casillas, A and Mohamed, KI and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long-COVID: II. SARS-CoV-2, extracellular vesicles, and neurological disorders.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {10}, pages = {1466-1485}, doi = {10.1002/jcb.30486}, pmid = {37801299}, issn = {1097-4644}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases/diagnosis/etiology ; *Extracellular Vesicles ; }, abstract = {With the decline in the number of new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, the World Health Organization announced the end of the SARS-CoV-2 pandemic. However, the repercussions of this viral pandemic may remain with us for a longer period of time, as it has remodeled the lives of humankind in many ways, including social and economic. Of course, its most important repercussions remain on the human health level. Long-coronavirus disease (COVID) or post-COVID is a state for which we do not have a concrete definition, a specific international classification of diseases Code, clear diagnostic tools, or well-known effective cures as of yet. In this second article from the Intrinsic Factors behind long-COVID Series, we try to link long-COVID symptoms with their causes, starting from the nervous system. Extracellular vesicles (ECVs) play very complex and ramified roles in the bodies of both healthy and not-healthy individuals. ECVs may facilitate the entry of many bioactive molecules and pathogens into the tissues and cells of the nervous system across the blood-brain barrier. Based on the size, quantity, and quality of their cargo, ECVs are directly proportional to the pathological condition and its severity through intertwined mechanisms that evoke inflammatory immune responses typically accompanied by pathological symptoms over variable time periods according to the type of these symptoms.}, } @article {pmid37800237, year = {2023}, author = {Gadelshina, D and Syunyakov, T and Gayduk, AJ and Borisova, O and Kuvshinova, N and Borisova, N and Gorbachev, D and Gonda, X and DeSousa, A and Yashikhina, A and Vlasov, A and Sheyfer, M and Kolsanov, A and Smirnova, D}, title = {Post-COVID Neuropsychiatric Complications in Children and Adolescents: a Study Design for Early Diagnosis and Treatment Using Innovative Technologies.}, journal = {Psychiatria Danubina}, volume = {35}, number = {Suppl 2}, pages = {256-262}, pmid = {37800237}, issn = {0353-5053}, mesh = {Humans ; Child ; Adolescent ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; *Mental Disorders/diagnosis/therapy ; Early Diagnosis ; COVID-19 Testing ; }, abstract = {BACKGROUND: The COVID-19 pandemic has had significant impacts on the child and adolescent population, with long-term consequences for physical health, socio-psychological well-being, and cognitive development, which require further investigation. We herein describe a study design protocol for recognizing neuropsychiatric complications associated with pediatric COVID-19, and for developing effective prevention and treatment strategies grounded on the evidence-based findings.

METHODS: The study includes two cohorts, each with 163 participants, aged from 7 to 18 years old, and matched by gender. One cohort consisted of individuals with a history of COVID-19, while the other group presents those without such a history. We undertake comprehensive assessments, including neuropsychiatric evaluations, blood tests, and validated questionnaires completed by parents/guardians and by the children themselves. The data analysis is based on machine learning techniques to develop predictive models for COVID-19-associated neuropsychiatric complications in children and adolescents.

RESULTS: The first model is focused on a binary classification to distinguish participants with and without a history of COVID-19. The second model clusters significant indicators of clinical dynamics during the follow-up observation period, including the persistence of COVID-19 related somatic and neuropsychiatric symptoms over time. The third model manages the predictors of discrete trajectories in the dynamics of post-COVID-19 states, tailored for personalized prediction modeling of affective, behavioral, cognitive, disturbances (academic/school performance), and somatic symptoms of the long COVID.

CONCLUSIONS: The current protocol outlines a comprehensive study design aiming to bring a better understanding of COVID-19-associated neuropsychiatric complications in a population of children and adolescents, and to create a mobile phone-based applications for the diagnosis and treatment of affective, cognitive, and behavioral conditions. The study will inform about the improved management of preventive and personalized care strategies for pediatric COVID-19 patients. Study results support the development of engaging and age-appropriate mobile technologies addressing the needs of this vulnerable population group.}, } @article {pmid37799164, year = {2023}, author = {Mata, R and Bankole, AO and Barnhill, J and Roth, I}, title = {A descriptive exploration of younger and older adults' experiences of Integrative Medical Group Visits for Long COVID.}, journal = {Aging and health research}, volume = {3}, number = {2}, pages = {}, pmid = {37799164}, issn = {2667-0321}, support = {K01 AT011578/AT/NCCIH NIH HHS/United States ; T32 NR007091/NR/NINR NIH HHS/United States ; T35 AG038047/AG/NIA NIH HHS/United States ; }, abstract = {INTRODUCTION: Long COVID disproportionately affects older adults. Individuals with Long COVID (LC) often experience symptoms that severely impact quality of life, and treatment approaches are still evolving. The Integrative Medical Group Visit (IMGV) model is an evidence-based approach that may be useful to treat patients with LC; however, there is limited evidence describing the experience and/or feasibility of using IMGV for LC treatment, especially among the older adult population. The purpose of this study is to describe older and younger adults' experiences of both having LC and participating in a virtually delivered IMGV for LC.

METHODS: This is a secondary analysis of qualitative data from a parent study examining the experiences of participants in a virtually delivered IMGV for patients with LC. Patients participated in semi-structured interviews before and after 8 weekly IMGV sessions. Thematic analysis was used to analyze interview data.

RESULTS: Overall, 21 pre-interviews and 17 post-interviews were collected. Thematic analysis of patient interviews by age group resulted in three themes that each contained similarities and differences between the younger and older adult participants. These themes included: (1) experiences of LC (2) feelings about the future (3) experiences of the pilot IMGV on LC.

CONCLUSION: This study provides critical context for clinicians who treat older adults with LC. Results support virtually delivered IMGVs as a potentially feasible option for both older and younger adults who want to apply an integrative approach to their LC treatment. Findings from this study will inform future research on IMGV for LC treatment.}, } @article {pmid37798930, year = {2023}, author = {Zamli, AH and Misnan, NA and Lim, SY and Zohdi, WNWM and Baharum, N and Andiappan, K}, title = {Post-COVID-19 Condition Characterization: Insights From a Cross-Sectional Study in a Malaysian Rehabilitation Center.}, journal = {Asia-Pacific journal of public health}, volume = {35}, number = {8}, pages = {516-523}, doi = {10.1177/10105395231203118}, pmid = {37798930}, issn = {1941-2479}, mesh = {Humans ; Cross-Sectional Studies ; *COVID-19 ; Rehabilitation Centers ; Asian People ; Fatigue/etiology ; }, abstract = {Although post-COVID-19 condition (PCC) is a major public health concern, studies on PCC in Southeast Asia are lacking. This study aimed to describe PCC symptoms and its functional impact among COVID-19 survivors undergoing outpatient rehabilitation in Malaysia. We evaluated 3037 patients with confirmed COVID-19, referred between November 2020 and September 2022, 3 to 6 months after infection. PCC was diagnosed in 71.1%. Fatigue and dyspnea were the most common symptoms. The PCC patients had reduced respiratory, ambulatory, and musculoskeletal function, and higher fatigue and pain scores, and were less likely to return to work (odds ratio [OR] = 0.55) compared with non-PCC patients. Recognition of PCC symptoms and its functional impact can guide early, tailored, rehabilitation interventions.}, } @article {pmid37798650, year = {2023}, author = {Vij, R and Kim, H and Park, H and Cheng, T and Lotfi, D and Chang, D}, title = {Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program.}, journal = {Stem cell research & therapy}, volume = {14}, number = {1}, pages = {287}, pmid = {37798650}, issn = {1757-6512}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Mesenchymal Stem Cell Transplantation/adverse effects/methods ; Treatment Outcome ; *Mesenchymal Stem Cells ; }, abstract = {BACKGROUND: Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences' autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome.

METHODS: Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 10[8] autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates.

RESULTS: VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen.

CONCLUSIONS: The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients' quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome.

TRIAL REGISTRATION: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. (https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2).}, } @article {pmid37797691, year = {2024}, author = {Mroueh, A and Fakih, W and Carmona, A and Trimaille, A and Matsushita, K and Marchandot, B and Qureshi, AW and Gong, DS and Auger, C and Sattler, L and Reydel, A and Hess, S and Oulehri, W and Vollmer, O and Lessinger, JM and Meyer, N and Pieper, MP and Jesel, L and Bäck, M and Schini-Kerth, V and Morel, O}, title = {COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {22}, number = {1}, pages = {286-299}, doi = {10.1016/j.jtha.2023.09.022}, pmid = {37797691}, issn = {1538-7836}, mesh = {Animals ; Humans ; *COVID-19/metabolism ; Cytokines/metabolism ; Endothelial Cells/metabolism ; Inflammation/metabolism ; Intercellular Adhesion Molecule-1/metabolism ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species/metabolism ; Sodium-Glucose Transporter 2/metabolism/pharmacology ; Swine ; Thrombin/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; *Vascular Diseases ; }, abstract = {BACKGROUND: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated.

OBJECTIVES: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin.

METHODS: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined.

RESULTS: Increased plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin.

CONCLUSION: In patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.}, } @article {pmid37797297, year = {2025}, author = {Delgado-Alonso, C and Díez-Cirarda, M and Pagán, J and Pérez-Izquierdo, C and Oliver-Mas, S and Fernández-Romero, L and Martínez-Petit, Á and Valles-Salgado, M and Gil-Moreno, MJ and Yus, M and Matías-Guiu, J and Ayala, JL and Matias-Guiu, JA}, title = {Unraveling brain fog in post-COVID syndrome: Relationship between subjective cognitive complaints and cognitive function, fatigue, and neuropsychiatric symptoms.}, journal = {European journal of neurology}, volume = {32}, number = {1}, pages = {e16084}, pmid = {37797297}, issn = {1468-1331}, support = {//Comunidad de Madrid/ ; //Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *COVID-19/complications/psychology ; Male ; *Fatigue/etiology/physiopathology ; Female ; Middle Aged ; Aged ; *Post-Acute COVID-19 Syndrome ; Adult ; Cognitive Dysfunction/etiology/physiopathology ; Neuropsychological Tests ; Depression/etiology ; Cognition/physiology ; Anxiety/etiology/psychology ; }, abstract = {BACKGROUND AND PURPOSE: "Brain fog" is a frequent and disabling symptom that can occur after SARS-CoV-2 infection. However, its clinical characteristics and the relationships among brain fog and objective cognitive function, fatigue, and neuropsychiatric symptoms (depression, anxiety) are still unclear. In this study, we aimed to examine the characteristics of brain fog and to understand how fatigue, cognitive performance, and neuropsychiatric symptoms and the mutual relationships among these variables influence subjective cognitive complaints.

METHODS: A total of 170 patients with cognitive complaints in the context of post-COVID syndrome were evaluated using a comprehensive neuropsychological protocol. The FLEI scale was used to characterize subjective cognitive complaints. Correlation analysis, regression machine-learning algorithms, and mediation analysis were calculated.

RESULTS: Cognitive complaints were mainly attention and episodic memory symptoms, while executive functions (planning) issues were less often reported. The FLEI scale, a mental ability questionnaire, showed high correlations with a fatigue scale and moderate correlations with the Stroop test, and anxiety and depressive symptoms. Random forest algorithms showed an R[2] value of 0.409 for the prediction of FLEI score, with several cognitive tests, fatigue and depression being the best variables used in the prediction. Mediation analysis showed that fatigue was the main mediator between objective and subjective cognition, while the effect of depression was indirect and mediated through fatigue.

CONCLUSIONS: Brain fog associated with COVID-19 is mainly characterized by attention and episodic memory, and fatigue, which is the main mediator between objective and subjective cognition. Our findings contribute to understanding the pathophysiology of brain fog and emphasize the need to unravel the main mechanisms underlying brain fog, considering several aspects.}, } @article {pmid37797257, year = {2023}, author = {Baker, MG and Kvalsvig, A and Plank, MJ and Geoghegan, JL and Wall, T and Tukuitonga, C and Summers, J and Bennett, J and Kerr, J and Turner, N and Roberts, S and Ward, K and Betty, B and Huang, QS and French, N and Wilson, N}, title = {Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.}, journal = {The New Zealand medical journal}, volume = {136}, number = {1583}, pages = {67-91}, doi = {10.26635/6965.6247}, pmid = {37797257}, issn = {1175-8716}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; New Zealand/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Maori People ; }, abstract = {In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.}, } @article {pmid37795061, year = {2023}, author = {Sapna, F and Deepa, F and Sakshi, F and Sonam, F and Kiran, F and Perkash, RS and Bendari, A and Kumar, A and Rizvi, Y and Suraksha, F and Varrassi, G}, title = {Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44588}, pmid = {37795061}, issn = {2168-8184}, abstract = {The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.}, } @article {pmid37793728, year = {2023}, author = {Grach, SL and Seltzer, J and Chon, TY and Ganesh, R}, title = {Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Mayo Clinic proceedings}, volume = {98}, number = {10}, pages = {1544-1551}, doi = {10.1016/j.mayocp.2023.07.032}, pmid = {37793728}, issn = {1942-5546}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Testing ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.}, } @article {pmid37792533, year = {2023}, author = {Ng, AHC and Hu, H and Wang, K and Scherler, K and Warren, SE and Zollinger, DR and McKay-Fleisch, J and Sorg, K and Beechem, JM and Ragaglia, E and Lacy, JM and Smith, KD and Marshall, DA and Bundesmann, MM and López de Castilla, D and Corwin, D and Yarid, N and Knudsen, BS and Lu, Y and Goldman, JD and Heath, JR}, title = {Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2.}, journal = {Cell reports}, volume = {42}, number = {10}, pages = {113212}, doi = {10.1016/j.celrep.2023.113212}, pmid = {37792533}, issn = {2211-1247}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Inflammation ; Immunity ; }, abstract = {Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.}, } @article {pmid37792437, year = {2023}, author = {Derksen, C and Rinn, R and Gao, L and Dahmen, A and Cordes, C and Kolb, C and Becker, P and Lippke, S}, title = {Longitudinal Evaluation of an Integrated Post-COVID-19/Long COVID Management Program Consisting of Digital Interventions and Personal Support: Randomized Controlled Trial.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e49342}, pmid = {37792437}, issn = {1438-8871}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Social Support ; }, abstract = {BACKGROUND: The postacute COVID-19 syndrome (PACS) can be addressed with multidisciplinary approaches, including professional support and digital interventions.

OBJECTIVE: This research aimed to test whether patients who received a health care facilitation program including medical internet support from human personal pilots and digital interventions (intervention group [IG] and active control group [ACG]) would experience fewer symptoms and have higher work ability and social participation than an untreated comparison group (CompG). The second objective was to compare the impact of a diagnostic assessment and digital interventions tailored to patients' personal capacity (IG) with that of only personal support and digital interventions targeting the main symptoms (ACG).

METHODS: In total, 1020 patients with PACS were recruited. Using a randomized controlled trial design between the IG and the ACG, as well as propensity score matching to include the CompG, analyses were run with logistic regression and hierarchical-linear models.

RESULTS: Symptoms decreased significantly in all groups over time (βT1-T2=0.13, t549=5.67, P<.001; βT2-T4=0.06, t549=2.83, P=.01), with a main effect of the group (β=-.15, t549=-2.65, P=.01) and a more pronounced effect in the IG and ACG compared to the CompG (between groups: βT1-T2=0.14, t549=4.31, P<.001; βT2-T4=0.14, t549=4.57, P<.001). Work ability and social participation were lower in the CompG, but there was no significant interaction effect. There were no group differences between the IG and the ACG.

CONCLUSIONS: Empowerment through personal pilots and digital interventions reduces symptoms but does not increase work ability and social participation. More longitudinal research is needed to evaluate the effects of a diagnostic assessment. Social support and digital interventions should be incorporated to facilitate health care interventions for PACS.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05238415; https://classic.clinicaltrials.gov/ct2/show/NCT05238415.

RR2-10.1186/s12879-022-07584-z.}, } @article {pmid37792410, year = {2023}, author = {Harris, E}, title = {US Survey: About 7% of Adults, 1% of Children Have Had Long COVID.}, journal = {JAMA}, volume = {330}, number = {16}, pages = {1516}, doi = {10.1001/jama.2023.19208}, pmid = {37792410}, issn = {1538-3598}, mesh = {Adult ; Child ; Humans ; COVID-19/complications/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology/etiology ; United States/epidemiology ; Health Surveys/statistics & numerical data ; }, } @article {pmid37790297, year = {2023}, author = {Cohen, AK and Jaudon, TW and Schurman, EM and Kava, L and Vogel, JM and Haas-Godsil, J and Lewis, D and Crausman, S and Leslie, K and Bligh, SC and Lizars, G and Davids, JD and Sran, S and Peluso, MJ and McCorkell, L}, title = {Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37790297}, issn = {2693-5015}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir.

METHODS: We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.5-30 days) of oral nirmatrelvir/ritonavir outside (n=11) of and within (n=2) the context of an acute SARS-CoV-2 infection. Participants reported on symptoms and health experiences before, during, and after their use of nirmatrelvir/ritonavir.

RESULTS: Among those who took a long course of nirmatrelvir/ritonavir outside of the context of an acute infection, some experienced a meaningful reduction in symptoms, although not all benefits persisted; others experienced no effect on symptoms. One participant reported intense stomach pain that precluded her from continuing her course. Among the two participants who took a long course of nirmatrelvir/ritonavir within the context of an acute reinfection, both eventually returned to their pre-re-infection baseline.

DISCUSSION: Long courses of nirmatrelvir/ritonavir may have meaningful benefits for some people with Long COVID but not others. We encourage researchers to study who, how, and why nirmatrelvir/ritonavir benefits some and what course length is most effective, with the goal of informing clinical recommendations for using nirmatrelvir/ritonavir and/or other antivirals as a potential treatment for Long COVID.}, } @article {pmid37789876, year = {2023}, author = {Wynberg, E and Verveen, A and van Willigen, HDG and Nieuwkerk, P and Davidovich, U and Lok, A and de Jong, MD and de Bree, GJ and Leenstra, T and Knoop, H and Prins, M and Boyd, A and , }, title = {Two-year trajectories of COVID-19 symptoms and their association with illness perception: A prospective cohort study in Amsterdam, the Netherlands.}, journal = {Influenza and other respiratory viruses}, volume = {17}, number = {10}, pages = {e13190}, pmid = {37789876}, issn = {1750-2659}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology ; Prospective Studies ; Netherlands/epidemiology ; SARS-CoV-2 ; Surveys and Questionnaires ; Perception ; }, abstract = {BACKGROUND: We used data from a prospective cohort to explore 2-year trajectories of 'long COVID' (persistent symptoms after SARS-CoV-2 infection) and their association with illness perception.

METHODS: RECoVERED participants (adults; prospectively enrolled following laboratory-confirmed SARS-CoV-2 infection, May 2020-June 2021) completed symptom questionnaires at months 2-12, 18 and 24, and the Brief Illness Perception Questionnaire (B-IPQ) at months 1, 6 and 12. Using group-based trajectory models (GBTM), we modelled symptoms (mean total numbers and proportion with four specific complaints), including age, sex, BMI and timing of infection as covariates. In a multivariable linear mixed-effects model, we assessed the association between symptom trajectories and repeated B-IPQ scores.

RESULTS: Among 292 participants (42% female; median age 51 [IQR = 36-62]), four trajectories were identified, ranging from Trajectory 4 (8.9%; 6 + symptoms) to Trajectory 1 (24.8%; no symptoms). The occurrence of fatigue and myalgia increased among 23% and 12% of participants, respectively. Individuals in Trajectory 4 experienced more negative adjusted B-IPQ scores over time than those in Trajectories 1-3.

CONCLUSIONS: We observed little fluctuation in the total number of symptoms, but individual symptoms may develop as others resolve. Reporting a greater number of symptoms was congruent with more negative illness perception over time.}, } @article {pmid37789860, year = {2023}, author = {Esposito, S and Deolmi, M and Ramundo, G and Puntoni, M and Caminiti, C and Principi, N}, title = {True prevalence of long COVID in children: a narrative review.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1225952}, pmid = {37789860}, issn = {1664-302X}, abstract = {Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children's emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.}, } @article {pmid37789266, year = {2023}, author = {Abu Hussein, N and Machahua, C and Ruchti, SC and Horn, MP and Piquilloud, L and Prella, M and Geiser, TK and von Garnier, C and Funke-Chambour, M}, title = {Circulating calprotectin levels four months after severe and non-severe COVID-19.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {650}, pmid = {37789266}, issn = {1471-2334}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *COVID-19 ; Critical Care ; Hospitals, University ; *Hypertension ; Leukocyte L1 Antigen Complex ; Lung ; }, abstract = {BACKGROUND: Calprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland.

METHODS: Calprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models.

RESULTS: Overall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001).

CONCLUSIONS: Serum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations.

TRIAL REGISTRATION: NCT04581135.}, } @article {pmid37788921, year = {2023}, author = {Barker-Davies, RM and O'Sullivan, O and Holdsworth, DA and Ladlow, P and Houston, A and Chamley, R and Greenhalgh, A and Nicol, ED and Bennett, AN}, title = {How long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort study.}, journal = {BMJ military health}, volume = {}, number = {}, pages = {}, doi = {10.1136/military-2023-002500}, pmid = {37788921}, issn = {2633-3775}, abstract = {INTRODUCTION: COVID-19 infection can precede, in a proportion of patients, a prolonged syndrome including fatigue, exercise intolerance, mood and cognitive problems. This study aimed to describe the profile of fatigue-related, exercise-related, mood-related and cognitive-related outcomes in a COVID-19-exposed group compared with controls.

METHODS: 113 serving UK Armed Forces participants were followed up at 5, 12 (n=88) and 18 months (n=70) following COVID-19. At 18 months, 56 were in the COVID-19-exposed group with 14 matched controls. Exposed participants included hospitalised (n=25) and community (n=31) managed participants. 43 described at least one of the six most frequent symptoms at 5 months: fatigue, shortness of breath, chest pain, joint pain, exercise intolerance and anosmia. Participants completed a symptom checklist, patient-reported outcome measures (PROMs), the National Institute for Health cognitive battery and a 6-minute walk test (6MWT). PROMs included the Fatigue Assessment Scale (FAS), Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Patient Checklist-5 (PCL-5) for post-traumatic stress.

RESULTS: At 5 and 12 months, exposed participants presented with higher PHQ-9, PCL-5 and FAS scores than controls (ES (effect size) ≥0.25, p≤0.04). By 12 months, GAD-7 was not significantly different to controls (ES <0.13, p=0.292). Remaining PROMs lost significant difference by 18 months (ES ≤0.11, p≥0.28). No significant differences in the cognitive scales were observed at any time point (F=1.96, p=0.167). At 5 and 12 months, exposed participants recorded significantly lower distances on the 6MWT (ηp [2]≥0.126, p<0.01). 6MWT distance lost significant difference by 18 months (ηp [2]<0.039, p>0.15).

CONCLUSIONS: This prospective cohort-controlled study observed adverse outcomes in depression, post-traumatic stress, fatigue and submaximal exercise performance up to 12 months but improved by 18-month follow-up, in participants exposed to COVID-19 compared with a matched control group.}, } @article {pmid37788721, year = {2023}, author = {Allgood, KL and Whittington, B and Xie, Y and Hirschtick, JL and Ro, A and Orellana, RC and Fleischer, NL}, title = {Social vulnerability and new mobility disability among adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2: Michigan COVID-19 Recovery Surveillance Study.}, journal = {Preventive medicine}, volume = {177}, number = {}, pages = {107719}, doi = {10.1016/j.ypmed.2023.107719}, pmid = {37788721}, issn = {1096-0260}, mesh = {Adult ; Humans ; *SARS-CoV-2 ; *COVID-19/diagnosis ; Social Vulnerability ; COVID-19 Testing ; Michigan/epidemiology ; }, abstract = {OBJECTIVE: Understanding the relationship between social factors and persistent COVID-19 health outcomes, such as onset of a disability after a SARS-CoV-2 (the virus that causes COVID-19) infection, is an increasingly important public health issue. The purpose of this paper is to examine associations between social vulnerability and new onset of a mobility disability post-COVID-19 diagnosis.

METHODS: We used data from the Michigan COVID-19 Recovery Surveillance Study, a population-based probability survey of adults with PCR-confirmed SARS-CoV-2 infection in Michigan between January 2020-May 2022 (n = 4295). We used the Minority Health Social Vulnerability Index (MHSVI), with high county-level social vulnerability defined at or above the 75th percentile. Mobility disability was defined as new difficulty walking or climbing stairs. We regressed mobility disability on the overall MHSVI, as well as sub-themes of the index (socioeconomic status, household composition/disability, minority and language, housing type, healthcare access, and medical vulnerability), using multivariable logistic regression, adjusting for age, race, sex, education, employment, and income.

RESULTS: Living in a county with high (vs. low) social vulnerability was associated with 1.38 times higher odds (95% confidence interval [CI]:1.18-1.61) of reporting a new mobility disability after a COVID-19 diagnosis after adjustment. Similar results were observed for the socioeconomic status and household composition/disability sub-themes. In contrast, residents of highly racially diverse counties had lower odds (odds ratio 0.74, 95% CI: 0.61, 0.89) of reporting a new mobility disability compared to low diversity counties.

CONCLUSIONS: Mitigating the effects of social vulnerabilities requires additional resources and attention to support affected individuals.}, } @article {pmid37788123, year = {2024}, author = {Kustura, L and Bobek, D and Poljičanin, A and Pavelin, S and Buljubašić Šoda, M and Šoda, J and Aksentijević, J and Duka Glavor, K and Narančić Knez, N and Viali, V and Cukrov, A and Todorić Laidlaw, I and Ipavec, N and Vukorepa, D and Stipica, I and Bakrač, K and Bošković, B and Mastelić, A and Režić Mužinić, N and Markotić, A and Đogaš, Z and Dolić, K and Rogić Vidaković, M}, title = {Psychometric properties and observational data for COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) for post-COVID-19 syndrome.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {117}, number = {1}, pages = {38-47}, doi = {10.1093/qjmed/hcad224}, pmid = {37788123}, issn = {1460-2393}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Psychometrics ; Reproducibility of Results ; Prospective Studies ; *COVID-19 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The recently developed modified COVID-19 (coronavirus of 2019) Yorkshire Rehabilitation Scale (C19-YRSm) captures comprehensive biopsychosocial components of WHO's International Classification of Functioning, Disability, and Health related to the Long Covid or post-COVID syndrome. The scale response categories on C19-YRSm were done post hoc on data collected from the original version of C19-YRS.

AIM: To evaluate the C19-YRSm scale using reliability and validity measures.

DESIGN: Prospective, observational study.

METHODS: The study includes 369 patients (clinical group) and 426 subjects of the general population (control group) and captures their post-COVID-19 symptoms. In addition, the reliability of C19-YRSm was estimated by Cronbach's alpha coefficients of internal consistency and inter-item correlations for subscales ('Symptom severity, Functional disability, and Other symptoms'). Convergent validity was established using correlations between C19-YRSm and Fatigue Severity Scale (FSS). The incremental validity of C19-YRSm was measured by introducing a hierarchical regression model using the C19-YRSm 'Overall health' subscale and FSS as criterion variables.

RESULTS: C19-YRSm subscales have excellent internal consistencies (Cronbach's α value 0.81-0.96) and acceptable inter-item correlations (r value 0.23-0.79). Hereafter, the convergent validity of the C19-YRSm is good due to significant correlations between C19-YRSm subscales and FSS and C19-YRSm subscales. Finally, the hierarchical regression analysis supported consistent evidence for the incremental validity of the C19-YRSm subscales.

CONCLUSION: C19-YRSm is a reliable and valid self-assessment scale for the assessment of post-COVID-19 syndrome.}, } @article {pmid37786966, year = {2023}, author = {Chollet, F and Leger, JM}, title = {Long COVID and cognition.}, journal = {European journal of neurology}, volume = {30}, number = {12}, pages = {3640-3641}, doi = {10.1111/ene.16082}, pmid = {37786966}, issn = {1468-1331}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cognition ; }, } @article {pmid37783406, year = {2024}, author = {Wasilewicz, A and Bojkova, D and Beniddir, MA and Cinatl, J and Rabenau, HF and Grienke, U and Rollinger, JM and Kirchweger, B}, title = {Molecular networking unveils anti-SARS-CoV-2 constituents from traditionally used remedies.}, journal = {Journal of ethnopharmacology}, volume = {319}, number = {Pt 2}, pages = {117206}, doi = {10.1016/j.jep.2023.117206}, pmid = {37783406}, issn = {1872-7573}, support = {P 34028/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *SARS-CoV-2 ; Caco-2 Cells ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Plant Extracts/therapeutic use ; Antiviral Agents/pharmacology/therapeutic use ; }, abstract = {Plants and fungi have a long tradition in ethnopharmacology for the treatment of infectious diseases including viruses. Many of these natural products have also been used to combat SARS-CoV-2 infections or symptoms of the post- and long-COVID form, owing to the scarcity of clinically approved therapeutics.

AIM OF THE STUDY: The ongoing threat posed by SARS-CoV-2, along with the rapidly evolving new variants, requires the development of new antiviral compounds. The aim of this study was to identify anti-SARS-CoV-2 herbal and fungal extracts used in traditional medicine against acute respiratory infection, inflammation, and related symptoms. Additionally, we sought to characterize their bioactive constituents.

MATERIALS AND METHODS: The antiviral activity and cell cytotoxicity of 179 herbal and fungal extracts were evaluated using two SARS-CoV-2 infection assays in Caco-2 cells. 19 plant extracts with and without anti-SARS-CoV-2 activity underwent detailed dereplication using molecular networking.

RESULTS: Extracts from Angelica sinensis (Oliv.) Diels roots, Annona squamosa L. seeds, Azadirachta indica A. Juss. fruits, Buddleja officinalis Maxim. flowers, Burkea africana Hook. bark and Clinopodium menthifolium (Host) Stace aerial parts showed a potent anti SARS-CoV-2 activity (IC50 < 5 μg/ml) with only moderate cytotoxicity (CC50 > 60 μg/ml, Caco-2). By performing the dereplication with a bioactivity-featured molecular network (MN) on the extract library level, rather than on the level of individual extracts, we could pinpoint compounds characteristic for active extracts. Thus, a straight-forward identification of potential anti-SARS-CoV-2 natural compounds was achieved prior to any fractionation or isolation efforts.

CONCLUSIONS: A sophisticated hyphenation of empirical knowledge with MS-based bioinformatics and automated compound annotation was applied to decipher the chemical space of the investigated extracts. The correlation with experimentally assessed anti-SARS-CoV-2 activities helped in predicting compound classes and structural elements relevant for the antiviral activities. Consequently, this accelerated the identification of constituents from the investigated mixtures with inhibitory effects against SARS-CoV-2.}, } @article {pmid37783167, year = {2023}, author = {Terai, H and Ishii, M and Takemura, R and Namkoong, H and Shimamoto, K and Masaki, K and Tanosaki, T and Chubachi, S and Matsuyama, E and Hayashi, R and Shimada, T and Shigematsu, L and Ito, F and Kaji, M and Takaoka, H and Kurihara, M and Nakagawara, K and Tomiyasu, S and Sasahara, K and Saito, A and Otake, S and Azekawa, S and Okada, M and Fukushima, T and Morita, A and Tanaka, H and Sunata, K and Asaoka, M and Nishie, M and Shinozaki, T and Ebisudani, T and Akiyama, Y and Mitsuishi, A and Nakayama, S and Ogawa, T and Sakurai, K and Irie, M and Yagi, K and Ohgino, K and Miyata, J and Kabata, H and Ikemura, S and Kamata, H and Yasuda, H and Kawada, I and Kimura, R and Kondo, M and Iwasaki, T and Ishida, N and Hiruma, G and Miyazaki, N and Ishibashi, Y and Harada, S and Fujita, T and Ito, D and Bun, S and Tabuchi, H and Kanzaki, S and Shimizu, E and Fukuda, K and Yamagami, J and Kobayashi, K and Hirano, T and Inoue, T and Haraguchi, M and Kagyo, J and Shiomi, T and Lee, H and Sugihara, K and Omori, N and Sayama, K and Otsuka, K and Miyao, N and Odani, T and Watase, M and Mochimaru, T and Satomi, R and Oyamada, Y and Masuzawa, K and Asakura, T and Nakayama, S and Suzuki, Y and Baba, R and Okamori, S and Arai, D and Nakachi, I and Kuwahara, N and Fujiwara, A and Oakada, T and Ishiguro, T and Isosno, T and Makino, Y and Mashimo, S and Kaido, T and Minematsu, N and Ueda, S and Minami, K and Hagiwara, R and Manabe, T and Fukui, T and Funatsu, Y and Koh, H and Yoshiyama, T and Kokuto, H and Kusumoto, T and Oashi, A and Miyawaki, M and Saito, F and Tani, T and Ishioka, K and Takahashi, S and Nakamura, M and Harada, N and Sasano, H and Goto, A and Kusaka, Y and Ohba, T and Nakano, Y and Nishio, K and Nakajima, Y and Suzuki, S and Yoshida, S and Tateno, H and Kodama, N and Shunsuke, M and Sakamoto, S and Okamoto, M and Nagasaki, Y and Umeda, A and Miyagawa, K and Shimada, H and Hagimura, K and Nagashima, K and Sato, T and Sato, Y and Hasegawa, N and Takebayashi, T and Nakahara, J and Mimura, M and Ogawa, K and Shimmura, S and Negishi, K and Tsubota, K and Amagai, M and Goto, R and Ibuka, Y and Kitagawa, Y and Kanai, T and Fukunaga, K}, title = {Comprehensive analysis of long COVID in a Japanese nationwide prospective cohort study.}, journal = {Respiratory investigation}, volume = {61}, number = {6}, pages = {802-814}, doi = {10.1016/j.resinv.2023.08.008}, pmid = {37783167}, issn = {2212-5353}, mesh = {Adult ; Female ; Humans ; Middle Aged ; *COVID-19/epidemiology ; East Asian People ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID.

METHODS: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications.

RESULTS: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID.

CONCLUSIONS: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan.}, } @article {pmid37782920, year = {2023}, author = {Hill, NS}, title = {In persistent dyspnea after COVID-19 ARDS, exercise training rehabilitation vs. usual PT reduced dyspnea at 90 d.}, journal = {Annals of internal medicine}, volume = {176}, number = {10}, pages = {JC117}, doi = {10.7326/J23-0073}, pmid = {37782920}, issn = {1539-3704}, mesh = {Humans ; *COVID-19/complications ; Dyspnea/etiology/therapy ; Exercise ; Exercise Therapy ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Respiratory Distress Syndrome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; }, abstract = {Romanet C, Wormser J, Fels A, et al. Effectiveness of exercise training on the dyspnoea of individuals with long COVID: a randomised controlled multicentre trial. Ann Phys Rehabil Med. 2023;66:101765. 37271020.}, } @article {pmid37781408, year = {2023}, author = {Augustin, M and Stecher, M and Wüstenberg, H and Di Cristanziano, V and Sandaradura de Silva, U and Picard, LK and Pracht, E and Rauschning, D and Gruell, H and Klein, F and Wenisch, C and Hallek, M and Schommers, P and Lehmann, C}, title = {15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status - longitudinal, observational, case-control study.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1226622}, pmid = {37781408}, issn = {1664-3224}, mesh = {Humans ; Case-Control Studies ; *COVID-19 ; COVID-19 Vaccines/administration & dosage ; Immunoglobulin G ; *Outpatients ; *Post-Acute COVID-19 Syndrome ; Risk Factors ; SARS-CoV-2 ; Vaccination ; Longitudinal Studies ; }, abstract = {BACKGROUND: While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear. Moreover, there is ongoing discussion about the effectiveness of post-infection vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) to aid in PCS recovery.

METHODS: In this longitudinal and observational case-control study we aimed at identifying long-term PCS courses and evaluating the effects of post-infection vaccinations on PCS recovery. Individuals with initial mild COVID-19 were followed for a period of 15 months after primary infection. We assessed PCS outcomes, distinct symptom clusters (SC), and SARS-CoV-2 immunoglobulin G (IgG) levels in patients who received SARS-CoV-2 vaccination, as well as those who did not. To identify potential associating factors with PCS, we used binomial regression models and reported the results as odds ratios (OR) with 95% confidence intervals (95%CI).

RESULTS: Out of 958 patients, follow-up data at 15 month after infection was obtained for 222 (23.2%) outpatients. Of those individuals, 36.5% (81/222) and 31.1% (69/222) were identified to have PCS at month 10 and 15, respectively. Fatigue and dyspnea (SC2) rather than anosmia and ageusia (SC1) constituted PCS at month 15. SARS-CoV-2 IgG levels were equally distributed over time among age groups, sex, and absence/presence of PCS. Of the 222 patients, 77.0% (171/222) were vaccinated between 10- and 15-months post-infection, but vaccination did not affect PCS recovery at month 15. 26.3% of unvaccinated and 25.8% of vaccinated outpatients improved from PCS (p= .9646). Baseline headache (SC4) and diarrhoea (SC5) were risk factors for PCS at months 10 and 15 (SC4: OR 1.85 (95%CI 1.04-3.26), p=.0390; SC5: OR 3.27(95%CI 1.54-6.64), p=.0009).

CONCLUSION: Based on the specific symptoms of PCS our findings show a shift in the pattern of recovery. We found no effect of SARS-CoV-2 vaccination on PCS recovery and recommend further studies to identify predicting biomarkers and targeted PCS therapeutics.}, } @article {pmid37780134, year = {2023}, author = {Ogbonna, O and Bull, F and Spinks, B and Williams, D and Lewis, R and Edwards, A}, title = {The Impact of Being Homeless on the Clinical Outcomes of COVID-19: Systematic Review.}, journal = {International journal of public health}, volume = {68}, number = {}, pages = {1605893}, pmid = {37780134}, issn = {1661-8564}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Ill-Housed Persons ; Mental Health ; }, abstract = {Objective: The homeless population experiences inequality in health compared with the general population, which may have widened during the COVID-19 pandemic. However, the impact of being homeless on the outcomes of COVID-19 is uncertain. This systematic review aimed to analyse the impact of experiencing homelessness on the clinical outcomes of COVID-19, including the effects on health inequalities. Methods: A review protocol was developed and registered in PROSPERO (PROSPERO registration 2022 CRD42022304941). Nine databases were searched in November 2022 to identify studies on homeless populations which contained primary research on the following outcomes of COVID-19: incidence, hospitalisation, mortality, long COVID, mental wellbeing, and evidence of inequalities. Included studies were summarised with narrative synthesis. Results: The searches yielded 8,233 initial hits; after screening, 41 studies were included. Overall, evidence showed that those in crowded living settings had a higher risk of COVID-19 infection compared to rough sleepers and the general population. The homeless population had higher rates of hospitalisation and mortality than the general population, lower vaccination rates, and suffered negative mental health impacts. Conclusion: This systematic review shows the homeless population is more susceptible to COVID-19 outcomes. Further research is needed to determine the actual impact of the pandemic on this population, and of interventions to mitigate overall risk, given the low certainty of findings from some of the low-quality evidence available. In addition, further research is required to ascertain the impact of long COVID on those experiencing homelessness, since the present review yielded no studies on this topic.}, } @article {pmid37777397, year = {2023}, author = {Seeley, MC and Gallagher, C and Colman, F and Lau, DH}, title = {Impact of Long-COVID on Australian Sufferers: Implications for Healthcare Planning.}, journal = {Heart, lung & circulation}, volume = {32}, number = {10}, pages = {e76-e77}, doi = {10.1016/j.hlc.2023.09.002}, pmid = {37777397}, issn = {1444-2892}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Australia/epidemiology ; *COVID-19/epidemiology ; Autonomic Nervous System ; Delivery of Health Care ; *Postural Orthostatic Tachycardia Syndrome ; }, } @article {pmid37777159, year = {2023}, author = {Antonelli, M and Penfold, RS and Canas, LDS and Sudre, C and Rjoob, K and Murray, B and Molteni, E and Kerfoot, E and Cheetham, N and Pujol, JC and Polidori, L and May, A and Wolf, J and Modat, M and Spector, T and Hammers, A and Ourselin, S and Steves, C}, title = {SARS-CoV-2 infection following booster vaccination: Illness and symptom profile in a prospective, observational community-based case-control study.}, journal = {The Journal of infection}, volume = {87}, number = {6}, pages = {506-515}, doi = {10.1016/j.jinf.2023.08.009}, pmid = {37777159}, issn = {1532-2742}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Humans ; Case-Control Studies ; *COVID-19/diagnosis/epidemiology/prevention & control ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; Vaccination ; Male ; Female ; }, abstract = {BACKGROUND: Booster COVID-19 vaccines have shown efficacy in clinical trials and effectiveness in real-world data against symptomatic and severe illness. However, some people still become infected with SARS-CoV-2 following a third (booster) vaccination. This study describes the characteristics of SARS-CoV-2 illness following a third vaccination and assesses the risk of progression to symptomatic disease in SARS-CoV-2 infected individuals with time since vaccination.

METHODS: This prospective, community-based, case-control study used data from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile application, self-reporting a first positive COVID-19 test between June 1, 2021 and April 1, 2022. To describe the characteristics of SARS-CoV-2 illness following a third vaccination, we selected cases and controls who had received a third and second dose of monovalent vaccination against COVID-19, respectively, and reported a first positive SARS-CoV-2 test at least 7 days after most recent vaccination. Cases and controls were matched (1:1) based on age, sex, BMI, time between first vaccination and infection, and week of testing. We used logistic regression models (adjusted for age, sex, BMI, level of social deprivation and frailty) to analyse associations of disease severity, overall disease duration, and individual symptoms with booster vaccination status. To assess for potential waning of vaccine effectiveness, we compared disease severity, duration, and symptom profiles of individuals testing positive within 3 months of most recent vaccination (reference group) to profiles of individuals infected between 3 and 4, 4-5, and 5-6 months, for both third and second dose. All analyses were stratified by time period, based on the predominant SARS-CoV-2 variant at time of infection (Delta: June 1, 2021-27 Nov, 2021; Omicron: 20 Dec, 2021-Apr 1, 2022).

FINDINGS: During the study period, 50,162 (Delta period) and 162,041 (Omicron) participants reported a positive SARS-CoV-2 test. During the Delta period, infection following three vaccination doses was associated with lower odds of long COVID (symptoms≥ 4 weeks) (OR=0.83, CI[0.50-1.36], p < 0.0001), hospitalisation (OR=0.55, CI[0.39-0.75], p < 0.0001) and severe symptoms (OR=0.36, CI[0.27-0.49], p < 0.0001), and higher odds of asymptomatic infection (OR=3.45, CI[2.86-4.16], p < 0.0001), compared to infection following only two vaccination doses. During the Omicron period, infection following three vaccination doses was associated with lower odds of severe symptoms (OR=0.48, CI[0.42-0.55], p < 0.0001). During the Delta period, infected individuals were less likely to report almost all individual symptoms after a third vaccination. During the Omicron period, individuals were less likely to report most symptoms after a third vaccination, except for upper respiratory symptoms e.g. sneezing (OR=1.40, CI[1.18-1.35], p < 0.0001), runny nose (OR=1.26, CI[1.18-1.35], p < 0.0001), sore throat (OR=1.17, CI[1.10-1.25], p < 0.0001), and hoarse voice (OR=1.13, CI[1.06-1.21], p < 0.0001), which were more likely to be reported. There was evidence of reduced vaccine effectiveness during both Delta and Omicron periods in those infected more than 3 months after their most recent vaccination, with increased reporting of severe symptoms, long duration illness, and most individual symptoms.

INTERPRETATION: This study suggests that a third dose of monovalent vaccine may reduce symptoms, severity and duration of SARS-CoV-2 infection following vaccination. For Omicron variants, the third vaccination appears to reduce overall symptom burden but may increase upper respiratory symptoms, potentially due to immunological priming. There is evidence of waning vaccine effectiveness against progression to symptomatic and severe disease and long COVID after three months. Our findings support ongoing booster vaccination promotion amongst individuals at high risk from COVID-19, to reduce severe symptoms and duration of illness, and health system burden. Disseminating knowledge on expected symptoms following booster vaccination may encourage vaccine uptake.}, } @article {pmid37775412, year = {2023}, author = {García Estévez, DA and López Pérez, Á and Gómez Márquez, H}, title = {Hyperbaric oxygen therapy in long-COVID-19 disease.}, journal = {Medicina clinica}, volume = {161}, number = {11}, pages = {498-499}, doi = {10.1016/j.medcli.2023.06.046}, pmid = {37775412}, issn = {1578-8989}, mesh = {Humans ; *Hyperbaric Oxygenation ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Oxygen ; }, } @article {pmid37774781, year = {2023}, author = {Bellanti, JA and Novak, P and Faitelson, Y and Bernstein, JA and Castells, MC}, title = {The Long Road of Long COVID: Specific Considerations for the Allergist/Immunologist.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {11}, number = {11}, pages = {3335-3345}, doi = {10.1016/j.jaip.2023.09.014}, pmid = {37774781}, issn = {2213-2201}, mesh = {Humans ; Allergists ; *COVID-19 ; *Diabetes Mellitus, Type 2 ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Post-Acute COVID-19 Syndrome ; Quality of Life ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {Long COVID (coronavirus disease 2019) syndrome, also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a new disorder that can develop after an acute infection with the SARS-CoV-2 virus. The condition is characterized by multiorgan system involvement with a wide range of symptoms that can vary in severity from mild to debilitating. Some of the common symptoms associated with long COVID syndrome include cardiovascular issues such as heart palpitations and chest pain; thrombotic events (eg, blood clotting disorders); metabolic problems (eg, type 2 diabetes); dysautonomia; paroxysmal orthostatic tachycardia syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; reactivation of the Epstein-Barr virus; the presence of autoantibodies; chronic spontaneous urticaria (hives); and connective tissue diseases. Whereas long COVID syndrome can affect individuals from various backgrounds, certain populations may be at higher risk such as individuals of Hispanic and Latino heritage, as well as those with low socioeconomic status, although approximately one-third of affected patients have no known risk factors or preexisting conditions. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. Whereas vaccination has been the most significant intervention able to decrease the severity of acute SARS-Cov2 infection and curtail deaths, limited data are available related to its modulating effect on long COVID necessitating the need for further investigation. Furthermore, several inflammatory pathways have been proposed for the pathogenesis of long COVID that are the targets for ongoing clinical studies evaluating novel pharmacological agents. The purpose of the present report is to review the many factors associated with long COVID with a focus on those aspects that have relevance to the allergist-immunologist.}, } @article {pmid37774184, year = {2023}, author = {Navani, A}, title = {A Multidisciplinary Rehabilitation Approach to Chronic Pain Patients in the Post-COVID-19 Era.}, journal = {Pain physician}, volume = {26}, number = {5}, pages = {457-466}, pmid = {37774184}, issn = {2150-1149}, mesh = {Humans ; *Chronic Pain/psychology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Systematic Reviews as Topic ; Chronic Disease ; }, abstract = {BACKGROUND: The global health care system has been shaken by the unprecedented pandemic. Chronic pain management has suffered through the pandemic due to lack of access and challenges in care delivery only to be faced by a new set of chronic pain conditions resulting from prolonged and persistent COVID-19 symptoms referred to as "long COVID syndrome."

OBJECTIVES: Long COVID is emerging as a complex and debilitating condition that occurs in a subpopulation of patients following acute COVID-19 infection. Our goals were to explore how to best treat and manage long COVID syndrome based on current experience.

METHODS: This is a perspective rather than a systematic review. It is based on the limited available literature and current clinical experience.

RESULTS: Although a few pharmacological agents have been proposed to mitigate symptoms, none have emerged to provide meaningful, long-term pain relief. Long COVID is associated with numerous and diverse symptoms. Risk factors for developing long COVID subsequent to acute COVID-19 remain unknown. Due to the multidimensional impact of long COVID chronic pain, a structured interdisciplinary rehabilitation model has been proposed to relieve pain, restore function, and maximize quality of life.

LIMITATIONS: This is a perspective with an editorial point of view rather than a systematic literature study. Long COVID syndrome is a new condition, with which no clinicians have extensive experience. This is not a systematic review so there is no Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram. This is not a clinical study so there was no need for institutional review board approvals.

CONCLUSIONS: Treatment goals for the postviral syndrome of long COVID are multifaceted. In addition to pain control, patients may have functional deficits, cognitive issues, mental health issues, and reduced quality of life. Thus, a structured interdisciplinary rehabilitation model seems most appropriate to manage long COVID.

KEY WORDS: Chronic pain, long COVID, pandemic, COVID-19, brain fog, fatigue, pain program, functional restoration, back pain, joint pain.}, } @article {pmid37773796, year = {2023}, author = {Toktaş, N and Köse, E and Lapa, TY and Kaas, ET and Serdar Yücel, A and Derman, S}, title = {Global trends and future prospects of COVID-19 and physical activity: Bibliometric analysis.}, journal = {Medicine}, volume = {102}, number = {39}, pages = {e35316}, pmid = {37773796}, issn = {1536-5964}, mesh = {Adolescent ; Child ; Humans ; Aged ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Exercise ; Bibliometrics ; }, abstract = {BACKGROUND: Containment measures implemented during the COVID-19 pandemic have led to drastic changes in daily life and effects on health behaviors such as decrease in physical activity (PA) levels. This study aims to present a general framework to researchers on COVID-19 and PA research in relation with changes in studies within years, current trend topics, gaps in the research field and possible future trends.

METHODS: A total of 1819 articles indexed in the WoS core collection database were analyzed according to publication year, citation, country and institution collaborations, coword, co-citation networks, concept-topic trends and topic clusters using bibliometric analysis.

RESULTS: The most productive country was the USA(n = 335), and the most productive institution was University of London in UK (n = 38). The most cited publication was the study by Ammar et al, (2020) (n = 188). In 2020, the most popular topics were PA and health meanwhile in 2021 behavior, lifestyle, social media and in 2022 habits, long COVID, sleep quality topics were in the foreground. Studies in 2023 focus on how COVID-19 affects PA habits and the associations between COVID-19-based anxiety and sleep patterns. These studies focused especially on effects of sport participation on life quality, diet, depression, mental health on young athletes, children, adolescent persons, older adult groups.

CONCLUSIONS: An important gap in the study area is research on effect of changing lifestyle due to pandemic on individuals and the society during the Post COVID-19 period. If benefits of PA will not be limited to only physical benefits and psychological emotional, cognitive and social benefits are also taken into consideration, it is important that researchers conduct long-term and widescale observations.}, } @article {pmid37773635, year = {2023}, author = {Weakley, KE and Schikler, A and Green, JV and Blatt, DB and Barton, SM and Statler, VA and Feygin, Y and Marshall, GS}, title = {Clinical Features and Follow-up of Referred Children and Young People With Long COVID.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {12}, pages = {1093-1099}, pmid = {37773635}, issn = {1532-0987}, mesh = {Adolescent ; Female ; Humans ; Male ; *COVID-19 ; Fatigue ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Patient-level data on the clinical features and outcomes of children and young people referred for possible long coronavirus disease (COVID) can guide clinicians on what to expect in managing patients and advising families.

METHODS: A Post-Acute COVID Clinic for persons <21 years of age was established in October 2020. Intake was standardized and management was tailored to presenting symptoms. Data were abstracted from the charts of all patients evaluated through December 2021, and the study cohort consisted of patients who had a history of confirmed severe acute respiratory syndrome coronavirus 2 infection, had ≥1 symptom persisting for ≥12 weeks and had no pre-existing diagnosis that explained the symptoms. A structured follow-up interview was conducted in early 2022.

RESULTS: A total of 104 patients were referred, 81 of whom met inclusion criteria. The median age was 14 years (interquartile range, 13-16), and most were female, White/Caucasian and had commercial health insurance. Patients reported previously good health but over half reported moderate-to-severe disability at their first visit. Two clusters of presenting symptoms-fatigue with multiple symptoms, and fatigue and headache with cardiopulmonary symptoms-were identified. Extensive routine testing did not affirm alternative diagnoses. Incident conditions-most commonly anxiety, depression and/or panic disorder; migraines; and autonomic dysfunction-were diagnosed on clinical grounds. Telephone interviews (N = 55) revealed that 78% of patients were improved by about 6 months.

CONCLUSIONS: Within the limits of a single-center, referral-based, observational cohort, this study provides reassurance to patients and parents in that most cases of long COVID were self-limited. Extensive evaluations may be more useful in ruling out alternative diagnoses than in affirming specific physiologic disturbances.}, } @article {pmid37773184, year = {2023}, author = {Gyöngyösi, M and Lukovic, D and Mester-Tonczar, J and Zlabinger, K and Einzinger, P and Spannbauer, A and Schweiger, V and Schefberger, K and Samaha, E and Bergler-Klein, J and Riesenhuber, M and Nitsche, C and Hengstenberg, C and Mucher, P and Haslacher, H and Breuer, M and Strassl, R and Puchhammer-Stöckl, E and Loewe, C and Beitzke, D and Hasimbegovic, E and Zelniker, TA}, title = {Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome.}, journal = {NPJ vaccines}, volume = {8}, number = {1}, pages = {145}, pmid = {37773184}, issn = {2059-0105}, support = {KLI 876/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {Epstein-Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021-May 2022 (median 243 days post-COVID-19 infection). DNA virus-related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus-related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).}, } @article {pmid37773124, year = {2023}, author = {Gjorgjievski, D and Stavrikj, K and Jordan, R and Adab, P and Stanoevski, G and Stamenova, A and Krstevska, E and Simonovska, S and Trpcheski, F and Adams, R and Easter, C and Rai, K and Cheng, KK and Chi, C and Cooper, BG and Correia-de-Sousa, J and Dickens, AP and Enocson, A and Gale, N and Jolly, K and Jowett, S and Maglakelidze, M and Maghlakelidze, T and Martins, S and Sitch, A and Stelmach, R and Turner, A and Williams, S and Farley, A}, title = {Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1887}, pmid = {37773124}, issn = {1471-2458}, support = {16/137/95/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Humans ; *Smoking Cessation/methods ; Crisis Intervention ; Feedback ; Republic of North Macedonia/epidemiology ; Smoking/epidemiology/therapy ; Nicotiana ; }, abstract = {INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care.

METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation.

RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses.

CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists.

TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.}, } @article {pmid37773092, year = {2023}, author = {Atalar, AÇ and Acarlı, ANÖ and Baykan, B and Martelletti, P and Bolay, H and Ertaş, M and Ekizoğlu, E and Karadaş, Ö and Polat, B and Gençdal, IY and Azorin, DG and Mitsikostas, D and Apostolakopoulou, L and Genç, H and Dikmen, PY and Demirel, EA and Aydınlar, EI and Gözübatık-Celik, RG and Shafiyev, J and Taşdelen, B and Özge, A}, title = {COVID-19 vaccination-related headache showed two different clusters in the long-term course: a prospective multicenter follow-up study (COVA-Head Study).}, journal = {The journal of headache and pain}, volume = {24}, number = {1}, pages = {132}, pmid = {37773092}, issn = {1129-2377}, mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; Follow-Up Studies ; COVID-19 Vaccines/adverse effects ; Prospective Studies ; *COVID-19/complications/prevention & control ; Headache/chemically induced/diagnosis ; *Migraine Disorders/diagnosis ; }, abstract = {BACKGROUND: Although acute headache following COVID-19 vaccination is widely acknowledged, the long-term progression of these headaches remains poorly understood. Our objective was to identify various phenotypes of prolonged or worsened headaches associated with COVID-19 vaccination and document any changes in these phenotypes over an extended period. Additionally, we aimed to document the diverse headache presentations among patients with pre-existing primary headaches.

METHODS: A multinational, prospective observational study was conducted to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires assessing COVID-19 vaccination-related headaches at three time points (initial visit, 3[rd] month follow-up, and 6th month follow-up) were developed for the study. Headache specialists/clinicians evaluated patients using these questionnaires in a prospective manner. Repeated K-means cluster analysis was performed to identify patient profiles with prolonged or worsened headaches related to COVID-19 vaccination.

RESULTS: Among the 174 patients included in the study, there was a female-to-male ratio of 128 (73.6%) to 46 (26.4%). The mean age of the patient group was 45.2 ± 13.3 years, and 107 patients (61.5%) had a pre-existing history of primary headaches. Through the analysis, two major clusters were identified based on headache characteristics at each visit. During the first visit (n = 174), Cluster 1 primarily comprised patients with a history of primary headaches, frontal localization of pain, throbbing pain type, more severe headaches accompanied by symptoms such as nausea, phonophobia, photophobia, and osmophobia, and worsened by physical activity. In contrast, Cluster 2 consisted of patients with longer headache durations (over one month) and a stabbing/pressing quality of pain. Patients in Cluster 1 had a higher prevalence of migraine as the pre-existing primary headache disorder compared to Cluster 2 (90.48% vs. 68.18%, respectively; p = 0.005).

CONCLUSION: The identification of two distinct phenotypes of prolonged or worsened headaches related to COVID-19 vaccination can provide valuable clinical insights. Having an awareness of the potential worsening of headaches following COVID-19 vaccination, particularly in patients with a primary headache disorder such as migraine, can help clinicians and headache experts anticipate and adjust their treatment strategies accordingly. This knowledge can aid in preplanning treatment modifications and optimize patient care.}, } @article {pmid37771872, year = {2023}, author = {Rasheed, MA and Ballotin, VR and Bigarella, LG and Soldera, J}, title = {Post-COVID-19 cholangiopathy: Systematic review.}, journal = {World journal of methodology}, volume = {13}, number = {4}, pages = {296-322}, pmid = {37771872}, issn = {2222-0682}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy.

AIM: To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.

METHODS: Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/).

RESULTS: The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes.

CONCLUSION: Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.}, } @article {pmid37771866, year = {2023}, author = {Sherif, ZA and Deverapalli, M and Challa, SR and Martirosyan, Z and Whitesell, P and Pizuorno, AM and Naqvi, Z and Tulloch, IK and Oskrochi, G and Brim, H and Ashktorab, H}, title = {Potential long-term neurological and gastrointestinal effects of COVID-19: A review of adult cohorts.}, journal = {World journal of methodology}, volume = {13}, number = {4}, pages = {323-336}, pmid = {37771866}, issn = {2222-0682}, abstract = {BACKGROUND: The respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a multi-organ disorder, with long-term effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease (COVID).

AIM: To examine the current knowledge and outcomes of long-term neurological and gastrointestinal (GI) symptoms in adult cohorts, including United States minority populations.

METHODS: PubMed and Google Scholar were searched using relevant terms, and data from five studies were analyzed, comprising 27383 patients with persistent neurological and GI sequelae.

RESULTS: The main symptoms included anxiety, depression, dysphagia, headache, vomiting, nausea, gastroesophageal reflux, fatigue, and abdominal pain. Patients with comorbidities and metabolic syndromes were at higher risk for long COVID. While most patients were European Americans, there was a need for further study on African Americans.

CONCLUSION: The underlying causes of these symptoms remain unclear, warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.}, } @article {pmid37770554, year = {2023}, author = {Vartanian, K and Fish, D and Kenton, N and Gronowski, B and Wright, B and Robicsek, A}, title = {Integrating patient-reported physical, mental, and social impacts to classify long COVID experiences.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {16288}, pmid = {37770554}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Mental Health ; Social Change ; Prospective Studies ; *COVID-19 ; Patient Reported Outcome Measures ; }, abstract = {Long COVID was originally identified through patient-reported experiences of prolonged symptoms. Many studies have begun to describe long COVID; however, this work typically focuses on medical records, instead of patient experiences, and lacks a comprehensive view of physical, mental, and social impacts. As part of our larger My COVID Diary (MCD) study, we captured patient experiences using a prospective and longitudinal patient-reported outcomes survey (PROMIS-10) and free-text narrative submissions. From this study population, we selected individuals who were still engaged in the MCD study and reporting poor health (PROMIS-10 scores < 3) at 6 months (n = 634). We used their PROMIS-10 and narrative data to describe and classify their long COVID experiences. Using Latent Class Analysis of the PROMIS-10 data, we identified four classifications of long COVID experiences: a few lingering issues (n = 107), significant physical symptoms (n = 113), ongoing mental and cognitive struggles (n = 235), and numerous compounding challenges (n = 179); each classification included a mix of physical, mental, and social health struggles with varying levels of impairment. The classifications were reinforced and further explained by patient narratives. These results provide a new understanding of the varying ways that long COVID presents to help identify and care for patients.}, } @article {pmid37770179, year = {2023}, author = {Kromydas, T and Demou, E and Edge, R and Gittins, M and Katikireddi, SV and Pearce, N and van Tongeren, M and Wilkinson, J and Rhodes, S}, title = {Occupational differences in the prevalence and severity of long-COVID: analysis of the Coronavirus (COVID-19) Infection Survey.}, journal = {Occupational and environmental medicine}, volume = {80}, number = {10}, pages = {545-552}, pmid = {37770179}, issn = {1470-7926}, support = {MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; 949582/ERC_/European Research Council/International ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; SPHSU17/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Occupations ; }, abstract = {OBJECTIVES: To establish whether prevalence and severity of long-COVID symptoms vary by industry and occupation.

METHODS: We used Office for National Statistics COVID-19 Infection Survey (CIS) data (February 2021-April 2022) of working-age participants (16-65 years). Exposures were industry, occupation and major Standard Occupational Classification (SOC) group. Outcomes were self-reported: (1) long-COVID symptoms and (2) reduced function due to long-COVID. Binary (outcome 1) and ordered (outcome 2) logistic regression were used to estimate odds ratios (OR)and prevalence (marginal means).

RESULTS: Public facing industries, including teaching and education, social care, healthcare, civil service, retail and transport industries and occupations, had the highest likelihood of long-COVID. By major SOC group, those in caring, leisure and other services (OR 1.44, 95% CIs 1.38 to 1.52) had substantially elevated odds than average. For almost all exposures, the pattern of ORs for long-COVID symptoms followed SARS-CoV-2 infections, except for professional occupations (eg, some healthcare, education, scientific occupations) (infection: OR<1 ; long-COVID: OR>1). The probability of reporting long-COVID for industry ranged from 7.7% (financial services) to 11.6% (teaching and education); whereas the prevalence of reduced function by 'a lot' ranged from 17.1% (arts, entertainment and recreation) to 22%-23% (teaching and education and armed forces) and to 27% (not working).

CONCLUSIONS: The risk and prevalence of long-COVID differs across industries and occupations. Generally, it appears that likelihood of developing long-COVID symptoms follows likelihood of SARS-CoV-2 infection, except for professional occupations. These findings highlight sectors and occupations where further research is needed to understand the occupational factors resulting in long-COVID.}, } @article {pmid37766216, year = {2023}, author = {Krivosikova, L and Kuracinova, T and Martanovic, P and Hyblova, M and Kaluzay, J and Uhrinova, A and Janega, P and Babal, P}, title = {Long COVID Complicated by Fatal Cytomegalovirus and Aspergillus Infection of the Lungs: An Autopsy Case Report.}, journal = {Viruses}, volume = {15}, number = {9}, pages = {}, pmid = {37766216}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications/pathology ; Cytomegalovirus ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Pulmonary Fibrosis/pathology ; Autopsy ; Lung/pathology ; *Aspergillosis/pathology ; }, abstract = {After the acute phase of COVID-19, some patients develop long COVID. This term is used for a variety of conditions with a complex, yet not fully elucidated etiology, likely including the prolonged persistence of the virus in the organism and progression to lung fibrosis. We present a unique autopsy case of a patient with severe COVID-19 with prolonged viral persistence who developed interstitial lung fibrosis complicated by a fatal combination of cytomegalovirus and Aspergillus infection. SARS-CoV-2 virus was detected at autopsy in the lungs more than two months after the acute infection, although tests from the nasopharynx were negative. Immune dysregulation after COVID-19 and the administration of corticoid therapy created favorable conditions for the cytomegalovirus and Aspergillus infection that were uncovered at autopsy. These pathogens may represent a risk for opportunistic infections, complicating not only the acute coronavirus infection but also long COVID, as was documented in the presented case.}, } @article {pmid37766108, year = {2023}, author = {Bourdas, DI and Bakirtzoglou, P and Travlos, AK and Andrianopoulos, V and Zacharakis, E}, title = {Exploring the Impact of COVID-19 on Physical Activity One Month after Infection and Its Potential Determinants: Re-Infections, Pre-Illness Vaccination Profiles/Types, and Beyond.}, journal = {Vaccines}, volume = {11}, number = {9}, pages = {}, pmid = {37766108}, issn = {2076-393X}, abstract = {This study investigated changes in physical activity (PA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while considering age, PA level, underlying medical conditions (UMCs), vaccination profiles/types, re-infections, disease severity, and treatment. Data were collected from 5829 respondents by using a validated web-based questionnaire. The findings showed that there was a significant overall decrease in PA (-16.2%), including in daily occupation (-11.9%), transportation (-13.5%), leisure-time (-16.4%), and sporting (-27.6%) activities. Age, PA level, UMCs, vaccination profiles/types, disease severity, and treatment played a role in determining PA in individuals' post-acute SARS-CoV-2 infections. Re-infections did not impact the decline in PA. Unvaccinated individuals experienced a significant decline in PA (-13.7%). Younger (-22.4%) and older adults (-22.5%), those with higher PA levels (-20.6%), those with 2-5 UMCs (-23.1%), those who were vaccinated (-16.9%) or partially vaccinated (-19.1%), those with mRNA-type vaccines only (-17.1%), those with recurrent (-19.4%)-to-persistent (-54.2%) symptoms, and those that required hospital (-51.8%) or intensive care unit (-67.0%) admission during their infections had more pronounced declines in PA. These findings emphasize the complex relationship between post-acute SARS-CoV-2 infection and PA and highlight the need for targeted interventions, further research, and multidisciplinary care to promote PA resumption and mitigate long-term effects on global public health.}, } @article {pmid37766091, year = {2023}, author = {Pongkunakorn, T and Manosan, T and Surawit, A and Ophakas, S and Mongkolsucharitkul, P and Pumeiam, S and Suta, S and Pinsawas, B and Sookrung, N and Saelim, N and Mahasongkram, K and Prangtaworn, P and Tungtrongchitr, A and Tangjittipokin, W and Mangmee, S and Boonnak, K and Narkdontri, T and Teerawattanapong, N and Wanitphadeedecha, R and Mayurasakorn, K}, title = {Immune Response after SARS-CoV-2 Infection with Residual Post-COVID Symptoms.}, journal = {Vaccines}, volume = {11}, number = {9}, pages = {}, pmid = {37766091}, issn = {2076-393X}, support = {R016534004//The Faculty of Medicine, Siriraj Hospital, Mahidol University/ ; }, abstract = {Many patients develop post-acute COVID syndrome (long COVID (LC)). We compared the immune response of LC and individuals with post-COVID full recovery (HC) during the Omicron pandemic. Two hundred ninety-two patients with confirmed COVID infections from January to May 2022 were enrolled. We observed anti-SARS-CoV-2 receptor-binding domain immunoglobulin G, surrogate virus neutralization test, T cell subsets, and neutralizing antibodies against Wuhan, BA.1, and BA.5 viruses (NeuT). NeuT was markedly reduced against BA.1 and BA.5 in HC and LC groups, while antibodies were more sustained with three doses and an updated booster shot than ≤2-dose vaccinations. The viral neutralization ability declined at >84-days after COVID-19 onset (PC) in both groups. PD1-expressed central and effector memory CD4[+] T cells, and central memory CD8[+] T cells were reduced in the first months PC in LC. Therefore, booster vaccines may be required sooner after the most recent infection to rescue T cell function for people with symptomatic LC.}, } @article {pmid37764085, year = {2023}, author = {Rivera-Cavazos, A and Luviano-García, JA and Garza-Silva, A and Morales-Rodríguez, DP and Kuri-Ayache, M and Sanz-Sánchez, MÁ and Santos-Macías, JE and Romero-Ibarguengoitia, ME and González-Cantú, A}, title = {Analyzing the Interplay between COVID-19 Viral Load, Inflammatory Markers, and Lymphocyte Subpopulations on the Development of Long COVID.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764085}, issn = {2076-2607}, abstract = {The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, including chronic inflammation and viral persistence, have been implicated in long COVID's pathogenesis. However, there are scarce studies in which multiple inflammatory markers and viral load are analyzed simultaneously in acute infection to determine how they predict for long COVID at long-term follow-up. This study explores the association between long COVID and inflammatory markers, viral load, and lymphocyte subpopulation during acute infection in hospitalized patients to better understand the risk factors of this disease. This longitudinal retrospective study was conducted in patients hospitalized with COVID-19 in northern Mexico. Inflammatory parameters, viral load, and lymphocyte subpopulation during the acute infection phase were analyzed, and long COVID symptoms were followed up depending on severity and persistence (weekly or monthly) and assessed 1.5 years after the acute infection. This study analyzed 79 patients, among them, 41.8% presented long COVID symptoms, with fatigue being the most common (45.5%). Patients with long COVID had higher lymphocyte levels during hospitalization, and NK cell subpopulation levels were also associated with long COVID. ICU admission during acute COVID-19 was also linked to the development of long COVID symptoms.}, } @article {pmid37763702, year = {2023}, author = {Falsetti, L and Zaccone, V and Santoro, L and Santini, S and Guerrieri, E and Giuliani, L and Viticchi, G and Cataldi, S and Gasbarrini, A and Landi, F and Santoliquido, A and Moroncini, G and On Behalf Of Gemelli Against Covid-Post-Acute Care Study Group, }, title = {The Relationship between Post-COVID Syndrome and the Burden of Comorbidities Assessed Using the Charlson Comorbidity Index.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {9}, pages = {}, pmid = {37763702}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Comorbidity ; Hospitalization ; }, abstract = {Introduction: The post-COVID-19 syndrome is a clinical entity characterized by the manifestation of signs and symptoms that develop after the acute phase of COVID-19, which persist for a duration of more than 12 weeks and are not explained by any alternative diagnosis. It has been observed that individuals with pre-existing chronic diseases, including cardiovascular and pulmonary diseases, are at a greater risk of developing post-COVID-19 syndrome. The Charlson Comorbidity Index (CCI) is a useful tool employed to evaluate the burden of comorbidities and predict the prognosis of patients with post-COVID-19 syndrome. The present study aims to assess whether the burden of comorbidities, evaluated using the CCI, correlates with post-COVID-19 syndrome. Materials and Methods: Between 21 April 2020 and 15 May 2023, we enrolled all consecutive outpatients with previous COVID-19 admissions to a post-acute day-hospital service three months after a negative SARS-CoV-2 molecular test. We assessed age, sex, BMI, acute COVID-19 and post-COVID-19 signs, and symptoms and calculated CCI according to its current definition. Post-COVID-19 syndrome was defined as the persistence of at least one sign or symptom lasting more than 12 weeks after COVID-19 resolution and not explained by an alternative diagnosis. The relationship between post-COVID-19 and CCI was explored first with the chi-squared test, then with different binary logistic regression models. We considered significant values of p lower than 0.05. Results: We obtained a cohort of 3636 patients and observed a significant association between the number of post-COVID-19 symptoms and CCI. Patients developing post-COVID-19 were more commonly affected by a greater burden of comorbidities. Patients with at least one CCI point had an increased risk of post-COVID-19 syndrome (OR:2.961; 95%CI: 2.269-3.863; p < 0.0001), which increased further for CCI ≥ 4 (OR:6.062; 95%CI: 3.163-11.618; p < 0.0001). Conclusions: Patients affected by post-COVID-19 show a greater clinical complexity and a larger burden of comorbidities, synthesized by a higher CCI; moreover, a higher CCI seems to correlate with an increasing post-COVID-19 risk, being the presence of ≥1 or ≥4 CCI points associated with a 3-fold and 6-fold increased risk of post-COVID-19 syndrome, respectively.}, } @article {pmid37763119, year = {2023}, author = {Asimakos, AT and Vassiliou, AG and Keskinidou, C and Spetsioti, S and Antonoglou, A and Vrettou, CS and Mourelatos, P and Diamantopoulos, A and Pratikaki, M and Athanasiou, N and Jahaj, E and Gallos, P and Kotanidou, A and Dimopoulou, I and Orfanos, SE and Katsaounou, P}, title = {Persistent Endothelial Lung Damage and Impaired Diffusion Capacity in Long COVID.}, journal = {Journal of personalized medicine}, volume = {13}, number = {9}, pages = {}, pmid = {37763119}, issn = {2075-4426}, abstract = {Since the beginning of the pandemic, both COVID-19-associated coagulopathy biomarkers and a plethora of endothelial biomarkers have been proposed and tested as prognostic tools of severity and mortality prediction. As the pandemic is gradually being controlled, attention is now focusing on the long-term sequelae of COVID-19. In the present study, we investigated the role of endothelial activation/dysfunction in long COVID syndrome. This observational study included 68 consecutive long COVID patients and a healthy age and sex-matched control group. In both groups, we measured 13 endothelial biomarkers. Moreover, in the long COVID patients, we evaluated fatigue and dyspnea severity, lung diffusion capacity (DLCO), and the 6-min walk (6MWT) test as measures of functional capacity. Our results showed that markers of endothelial activation/dysfunction were higher in long COVID patients, and that soluble intracellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) negatively correlated with lung diffusion and functional capacity (sICAM-1 vs. DLCO, r = -0.306, p = 0.018; vs. 6MWT, r = -0.263, p = 0.044; and sVCAM-1 vs. DLCO, r= -0.346, p = 0.008; vs. 6MWT, r = -0.504, p < 0.0001). In conclusion, evaluating endothelial biomarkers alongside clinical tests might yield more specific insights into the pathophysiological mechanisms of long COVID manifestations.}, } @article {pmid37763088, year = {2023}, author = {Gallo, A and Covino, M and Lipari, A and Pellegrino, S and Ibba, F and Agnitelli, MC and Tosato, M and Landi, F and Montalto, M and Gemelli Against Covid-Post-Acute Care Team, }, title = {Increase in Chronic Medications and Polypharmacy-The Multifaceted Burden of COVID-19 Disease on Public Health Care.}, journal = {Journal of personalized medicine}, volume = {13}, number = {9}, pages = {}, pmid = {37763088}, issn = {2075-4426}, abstract = {The long-term impact of COVID-19 disease is becoming a major global concern. In this retrospective monocentric analysis, we included consecutive subjects admitted to our COVID-19 Post-Acute Care Service for a SARS-CoV-2 infection that occurred between three and twelve months before. A home medication list relative to the period before SARS-CoV-2 infection (baseline) was recorded and compared with that one relative to the time of outpatient visit (follow-up). Drugs were coded according to the Anatomical Therapeutic Chemical Classification (ATC) System. In a total of 2007 subjects, at follow-up, a significant increase with respect to baseline was reported in the total median number of chronic medications (two [0-4] vs. one [0-3]) and in specific ATC-group drugs involving the alimentary, blood, cardiovascular, genitourinary, muscle-skeletal, nervous and respiratory systems. In a multivariate analysis, COVID-19 disease severity and age > 65 years resulted in the best predictors for an increase in the number of medications, while anti-SARS-CoV-2 vaccination played a significant protective role. The long-term care of patients infected by COVID-19 may be more complex than reported so far. Multidisciplinary and integrated care pathways should be encouraged, mainly in older and frailer subjects and for patients experiencing a more severe disease. Vaccination may also represent a fundamental protection against long-term sequelae.}, } @article {pmid37762851, year = {2023}, author = {Muench, A and Lampe, EW and Boyle, JT and Seewald, M and Thompson, MG and Perlis, ML and Vargas, I}, title = {The Assessment of Post-COVID Fatigue and Its Relationship to the Severity and Duration of Acute COVID Illness.}, journal = {Journal of clinical medicine}, volume = {12}, number = {18}, pages = {}, pmid = {37762851}, issn = {2077-0383}, support = {K23 HL141581/HL/NHLBI NIH HHS/United States ; K24 AG055602/AG/NIA NIH HHS/United States ; }, abstract = {Emerging data suggests that COVID-19 is associated with fatigue well beyond the acute illness period. The present analysis aimed to: (1) characterize the prevalence and incidence of high fatigue at baseline and follow-up; (2) examine the impact of COVID-19 diagnosis on fatigue level following acute illness; and (3) examine the impact of acute COVID-19 symptom severity and duration on fatigue at follow-up. Subjects (n = 1417; 81.0% female; 83.3% White; X¯age = 43.6 years) completed the PROMIS-Fatigue during the initial wave of the pandemic at baseline (April-June 2020) and 9-month follow-up (January-March 2021). A generalized linear model (binomial distribution) was used to examine whether COVID-19 positivity, severity, and duration were associated with higher fatigue level at follow-up. Prevalence of high fatigue at baseline was 21.88% and 22.16% at follow-up, with 8.12% new cases at follow-up. Testing positive for COVID-19 was significantly associated with higher fatigue at follow-up. COVID-19 symptom duration and severity were significantly associated with increased fatigue at follow-up. COVID-19 symptom duration and severity during acute illness may precipitate longer-term fatigue, which could have implications for treatment planning and future research. Future studies should further evaluate the relationship between symptom severity, duration, and fatigue.}, } @article {pmid37761758, year = {2023}, author = {Reis, N and Costa Dias, MJ and Sousa, L and Canedo, F and Rico, MT and Henriques, MA and Baixinho, CL}, title = {Telerehabilitation Intervention in Transitional Care for People with COVID-19: Pre-Post Study with a Non-Equivalent Control Group.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {18}, pages = {}, pmid = {37761758}, issn = {2227-9032}, abstract = {SARS-CoV-2 infection and its resulting sequelae have increased the prevalence of people with respiratory symptoms, with impacts on functional capacity, quality of life, anxiety, depression, and mental health. To mitigate this problem, one challenge has been the design and implementation of interventions that simultaneously allow for education, rehabilitation, and monitoring of people with long COVID, at a time when health services were on the verge of rupture due to the volume of people with active COVID and in need of intensive care. Telerehabilitation emerged as a mode for providing rehabilitative care that brought professionals closer to patients and enabled continuity of care. The present study aimed to evaluate the results of a telerehabilitation intervention for people with injuries associated with SARS-CoV-2 infection in hospital-community transitions, considering their degree of dependence in performing activities of daily living, respiratory symptoms, fatigue, gait capacity, muscle strength, and experience with anxiety and depression. A pre-post study with a non-equivalent control group was carried out with a total of 49 participants (intervention group n = 24; control group n = 25). The post-intervention results showed an increase in saturation, a decrease in heart rate, an improvement in the impact of post-COVID functionality, a decrease in fatigue, a decrease in perceived effort, and a decrease in depressive and anxiety symptoms. The telerehabilitation intervention, which combined educational strategies with respiratory and motor rehabilitation, helped improve global functionality and self-care, with clinical and functional impacts.}, } @article {pmid37761716, year = {2023}, author = {Calvache-Mateo, A and Heredia-Ciuró, A and Martín-Núñez, J and Hernández-Hernández, S and Reychler, G and López-López, L and Valenza, MC}, title = {Efficacy and Safety of Respiratory Telerehabilitation in Patients with Long COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {18}, pages = {}, pmid = {37761716}, issn = {2227-9032}, support = {19/02609//Ministerio de educación, cultura y deporte (ES)/ ; 20/01670//Ministerio de educación, cultura y deporte (ES)/ ; 21/00451//Ministerio de educación, cultura y deporte (ES)/ ; }, abstract = {The aim of this review was to identify, map, and synthesize the extent and nature of research activity on the use of telerehabilitation to support Long COVID-19 rehabilitation and examine the efficacy and safety of respiratory telerehabilitation in patients with Long COVID-19. A systematic review and meta-analysis of randomized controlled trials were performed. We included controlled trials that tested the effect of respiratory telerehabilitation interventions in patients with Long COVID-19 versus no intervention, usual care, placebo, or face-to-face intervention. The data were pooled, and a meta-analysis was completed for quality of life, dyspnea, lung function, anxiety and depression, respiratory muscle strength, functional capacity, and lower limb strength. Finally, 10 studies were included. The meta-analysis results show significant differences in favor of respiratory telerehabilitation in quality of life (p = 0.02), dyspnea (p < 0.00001), respiratory muscle strength (p < 0.001), functional capacity (p < 0.0001), and lower limb strength (p = 0.01) but not in lung function (p = 0.28) and anxiety and depression (p = 0.55). In addition, there were no statistically significant differences in adverse effects (p = 0.06) between the telerehabilitation and comparator groups. The results suggest that these interventions can improve quality of life, reduce dyspnea, and increase respiratory and lower extremity muscle strength as well as functional capacity in patients with Long COVID-19.}, } @article {pmid37761479, year = {2023}, author = {Buonsenso, D and Camporesi, A and Morello, R and De Rose, C and Fracasso, M and Chieffo, DPR and Valentini, P}, title = {Social Stigma in Children with Long COVID.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {37761479}, issn = {2227-9067}, abstract = {UNLABELLED: There is growing evidence that adults with Long COVID suffer from different sets of stigmata related to their condition. In children with Long COVID, this aspect has never been investigated. This study aims to investigate if children with Long COVID also experience stigma.

METHODS: Children with a previous SARS-CoV-2 infection evaluated at 3 month follow-ups in a pediatric post COVID unit were asked to fill in an online Long COVID Stigma Scale survey before they were assessed by a pediatrician. Doctors were unaware of children's responses when they performed a diagnosis of Long COVID or full recovery from previous infection, according to the World Health Organization definition of pediatric Long COVID. Responses to the Stigma scale were then compared in the two cohorts of children.

RESULTS: 224 patients responded to the questionnaire; 40 patients were diagnosed with Long COVID. Children with Long COVID significantly more frequently felt embarrassed about having Long COVID (p 0.035), felt embarrassed about having physical limitations (p < 0.001), felt they were valued less due to Long COVID (p 0.003), felt they were different from other peers due to Long COVID (p 0.033), felt significantly more frequently that people behaved differently towards them because they might be lying since the diagnosis of Long COVID (p 0.006), that they were less respected by others due to Long COVID (p 0.017), that other people thought that Long COVID is not a real disease (p 0.007), that other people thought that developing Long COVID is a sign of weakness (p 0.008), and that other people might judge them negatively due to their diagnosis of Long COVID (p < 0.001).

CONCLUSIONS: Children with Long COVID, similar to adults, are suffering from stigmata due to their condition,. These data may have implication and should be used by the public, policy makers, and healthcare professionals regarding pediatric Long COVID.}, } @article {pmid37760965, year = {2023}, author = {Boura, I and Qamar, MA and Daddoveri, F and Leta, V and Poplawska-Domaszewicz, K and Falup-Pecurariu, C and Ray Chaudhuri, K}, title = {SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, pmid = {37760965}, issn = {2227-9059}, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson's disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions.}, } @article {pmid37759738, year = {2023}, author = {Rubio-Casillas, A and Redwan, EM and Uversky, VN}, title = {Does SARS-CoV-2 Induce IgG4 Synthesis to Evade the Immune System?.}, journal = {Biomolecules}, volume = {13}, number = {9}, pages = {}, pmid = {37759738}, issn = {2218-273X}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Immunoglobulin G ; T-Lymphocytes ; Killer Cells, Natural ; }, abstract = {SARS-CoV-2, the virus that causes the COVID-19 disease, has been shown to cause immune suppression in certain individuals. This can manifest as a reduced ability of the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm", an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely understood at this time, and research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this study, we propose the hypothesis that IgG4 antibodies produced by B cells in response to infection by SARS-CoV-2 generate immunological tolerance, which prevents its elimination and leads to persistent and chronic infection. In summary, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.}, } @article {pmid37759493, year = {2023}, author = {Zingaropoli, MA and Pasculli, P and Barbato, C and Petrella, C and Fiore, M and Dominelli, F and Latronico, T and Ciccone, F and Antonacci, M and Liuzzi, GM and Talarico, G and Bruno, G and Galardo, G and Pugliese, F and Lichtner, M and Mastroianni, CM and Minni, A and Ciardi, MR}, title = {Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19.}, journal = {Cells}, volume = {12}, number = {18}, pages = {}, pmid = {37759493}, issn = {2073-4409}, mesh = {Humans ; Male ; Female ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Brain ; Biomarkers ; Disease Progression ; }, abstract = {Background: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. Materials and Methods: In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost). Patients were stratified according to COVID-19 severity based on acute respiratory distress syndrome (ARDS) onset (severe and non-severe groups). A further stratification according to the presence of NS (with and without groups) at baseline (requiring a puncture lumbar for diagnostic purposes) and according to NS self-referred at Tpost was performed. Finally, cerebrospinal fluid (CSF) samples were collected from patients with NS present at baseline. Results: We enrolled 144 COVID-19 patients (62 female/82 male; median age [interquartile range, IQR]): 64 [55-77]) and 53 heathy donors (HD, 30 female/23 male; median age [IQR]: 64 [59-69]). At baseline, higher plasma levels of NfL, GFAP and sCD163 in COVID-19 patients compared to HD were observed (p < 0.0001, p < 0.0001 and p < 0.0001, respectively), especially in those with severe COVID-19 (p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Patients with NS showed higher plasma levels of NfL, GFAP and sCD163 compared to those without (p = 0.0023, p < 0.0001 and 0.0370, respectively). At baseline, in COVID-19 patients with NS, positive correlations between CSF levels of sCD163 and CSF levels of NfL (ρ = 0.7536, p = 0.0017) and GFAP were observed (ρ = 0.7036, p = 0.0045). At Tpost, the longitudinal evaluation performed on 77 COVID-19 patients showed a significant reduction in plasma levels of NfL, GFAP and sCD163 compared to baseline (p < 0.0001, p < 0.0001 and p = 0.0413, respectively). Finally, at Tpost, in the severe group, higher plasma levels of sCD163 in patients with NS compared to those without were reported (p < 0.0001). Conclusions: High plasma levels of NfL, GFAP and sCD163 could be due to a proinflammatory systemic and brain response involving microglial activation and subsequent CNS damage. Our data highlight the association between myeloid activation and CNS perturbations.}, } @article {pmid37759324, year = {2023}, author = {Roggeman, S and Jimenez Garcia, BG and Leemans, L and Demol, J and Geers, J and De Smedt, A and Putman, K and Schiltz, M and Beckwée, D and De Waele, E}, title = {Functional performance recovery after individualized nutrition therapy combined with a patient-tailored physical rehabilitation program versus standard physiotherapy in patients with long COVID: a pilot study.}, journal = {Pilot and feasibility studies}, volume = {9}, number = {1}, pages = {166}, pmid = {37759324}, issn = {2055-5784}, support = {LCOV21-1306//Belgian Health Care Knowledge Centre/ ; }, abstract = {BACKGROUND: Long COVID is suggested to be present in 14 to 43% of COVID 19-survivors. Literature on this new condition states a need for a multidisciplinary approach including physical exercise and nutrition. The aim of the current pilot study is to investigate the feasibility of the proposed protocol to prepare for a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment compared to standard physiotherapy.

METHODS: This is a protocol of the UNLOCK (Nutrition and LOComotoric rehabilitation in long COVID) study, a pragmatic, single center, randomized controlled pilot trial with two groups. Patients with persisting symptoms related to a SARS-CoV-2 infection will receive either standard physiotherapy or a personalized multimodal treatment for a period of 12 weeks, consisting of individualized physical exercise program combined with individualized nutritional therapy. They will be followed-up at 6, 12, and 18 weeks after randomization.

DISCUSSION: A multidisciplinary approach for dealing with long COVID is needed. Because of the lack of clear data and the fact that this is a very heterogenic group, we aim to prepare and optimize a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05254301 (since February 24, 2022).}, } @article {pmid37758654, year = {2023}, author = {Pasea, L and Dashtban, A and Mizani, M and Bhuva, A and Morris, T and Mamza, JB and Banerjee, A}, title = {Risk factors, outcomes and healthcare utilisation in individuals with multimorbidity including heart failure, chronic kidney disease and type 2 diabetes mellitus: a national electronic health record study.}, journal = {Open heart}, volume = {10}, number = {2}, pages = {}, pmid = {37758654}, issn = {2053-3624}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology ; Electronic Health Records ; Multimorbidity ; Retrospective Studies ; Risk Factors ; Patient Acceptance of Health Care ; *Heart Failure/diagnosis/epidemiology/therapy ; *Renal Insufficiency, Chronic/diagnosis/epidemiology/therapy ; }, abstract = {BACKGROUND: Heart failure (HF), type 2 diabetes (T2D) and chronic kidney disease (CKD) commonly coexist. We studied characteristics, prognosis and healthcare utilisation of individuals with two of these conditions.

METHODS: We performed a retrospective, population-based linked electronic health records study from 1998 to 2020 in England to identify individuals diagnosed with two of: HF, T2D or CKD. We described cohort characteristics at time of second diagnosis and estimated risk of developing the third condition and mortality using Kaplan-Meier and Cox regression models. We also estimated rates of healthcare utilisation in primary care and hospital settings in follow-up.

FINDINGS: We identified cohorts of 64 226 with CKD and HF, 82 431 with CKD and T2D, and 13 872 with HF and T2D. Compared with CKD and T2D, those with CKD and HF and HF and T2D had more severe risk factor profile. At 5 years, incidence of the third condition and all-cause mortality occurred in 37% (95% CI: 35.9%, 38.1%%) and 31.3% (30.4%, 32.3%) in HF+T2D, 8.7% (8.4%, 9.0%) and 51.6% (51.1%, 52.1%) in HF+CKD, and 6.8% (6.6%, 7.0%) and 17.9% (17.6%, 18.2%) in CKD+T2D, respectively. In each of the three multimorbid groups, the order of the first two diagnoses was also associated with prognosis. In multivariable analyses, we identified risk factors for developing the third condition and mortality, such as age, sex, medical history and the order of disease diagnosis. Inpatient and outpatient healthcare utilisation rates were highest in CKD and HF, and lowest in CKD and T2D.

INTERPRETATION: HF, CKD and T2D carry significant mortality and healthcare burden in combination. Compared with other disease pairs, individuals with CKD and HF had the most severe risk factor profile, prognosis and healthcare utilisation. Service planning, policy and prevention must take into account and monitor data across conditions.}, } @article {pmid37756608, year = {2023}, author = {Yamamoto, S and Matsuda, K and Maeda, K and Horii, K and Okudera, K and Oshiro, Y and Inamura, N and Nemoto, T and Takeuchi, JS and Li, Y and Konishi, M and Tsuchiya, K and Gatanaga, H and Oka, S and Mizoue, T and Sugiyama, H and Aoyanagi, N and Mitsuya, H and Sugiura, W and Ohmagari, N}, title = {Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {12}, pages = {1652-1661}, doi = {10.1093/infdis/jiad317}, pmid = {37756608}, issn = {1537-6613}, support = {2020-B-09//Japan Health Research Promotion Bureau/ ; 19K059//National Center for Global Health and Medicine/ ; //Abbott Japan/ ; //Roche Diagnostics/ ; //Roche/ ; //Diagnostics/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Antibodies, Neutralizing ; Breakthrough Infections ; COVID-19 Vaccines ; Propensity Score ; *COVID-19 ; SARS-CoV-2 ; Antibodies, Viral ; }, abstract = {BACKGROUND: Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development.

METHODS: We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti-receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID.

RESULTS: Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%-77%) and 72% (95% CI, 53%-83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID.

CONCLUSIONS: Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID.}, } @article {pmid37756137, year = {2023}, author = {Adjaye-Gbewonyo, D and Vahratian, A and Perrine, CG and Bertolli, J}, title = {Long COVID in Adults: United States, 2022.}, journal = {NCHS data brief}, volume = {}, number = {480}, pages = {1-8}, pmid = {37756137}, issn = {1941-4935}, abstract = {People who have had COVID-19 may continue to have symptoms or develop new symptoms months after being infected with SARS-CoV-2 (1). This can lead to long-term health and economic impacts on those affected and on society (2). This report uses data from the 2022 National Health Interview Survey to describe the percentage of adults who ever had or had Long COVID at the time of interview (currently have Long COVID) by sociodemographic and geographic characteristics. Long COVID was defined as self-reporting the presence of symptoms for at least 3 months after having COVID-19 among those who reported either a positive test or a doctor's diagnosis of COVID-19.}, } @article {pmid37756128, year = {2023}, author = {Vahratian, A and Adjaye-Gbewonyo, D and Lin, JS and Saydah, S}, title = {Long COVID in Children: United States, 2022.}, journal = {NCHS data brief}, volume = {}, number = {479}, pages = {1-6}, pmid = {37756128}, issn = {1941-4935}, abstract = {While most individuals who contract COVID-19 feel better within a few weeks, others have new, returning, or ongoing symptoms that they did not have before COVID-19, which is often referred to as Long COVID (1). This report describes the percentage of children ages 0-17 years who ever had Long COVID or had Long COVID at the time of interview (currently have Long COVID) based on parent-reported data from the 2022 National Health Interview Survey (NHIS). Long COVID was defined as the presence of symptoms for at least 3 months after having COVID-19 among those who received either a positive test or a doctor's diagnosis of COVID-19.}, } @article {pmid37755922, year = {2023}, author = {Harris, E}, title = {Exercise Programs Might Improve Long COVID.}, journal = {JAMA}, volume = {330}, number = {15}, pages = {1421}, doi = {10.1001/jama.2023.18739}, pmid = {37755922}, issn = {1538-3598}, mesh = {Humans ; COVID-19/complications/therapy ; Exercise ; *Exercise Therapy ; *Post-Acute COVID-19 Syndrome/therapy ; }, } @article {pmid37754658, year = {2023}, author = {Mancino, E and Nenna, R and Matera, L and La Regina, DP and Petrarca, L and Iovine, E and Di Mattia, G and Frassanito, A and Conti, MG and Bonci, E and Spatuzzo, M and Ialongo, S and Zicari, AM and Spalice, A and Midulla, F and On Behalf Of The Long Covid Research Group, }, title = {A Single Center Observational Study on Clinical Manifestations and Associated Factors of Pediatric Long COVID.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {18}, pages = {}, pmid = {37754658}, issn = {1660-4601}, mesh = {Humans ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Family ; Anosmia ; *Hypersensitivity, Immediate ; }, abstract = {Children with SARS-CoV-2 are mostly mild symptomatic, but they may develop conditions, such as persisting symptoms, that may put them at greater risk of complications. Our aim was to evaluate the frequency and the presence of risk factors for persisting COVID-19 symptoms in children. We carried out a prospective observational study of the clinical manifestation of Long COVID at the Department of Maternal Infantile Science of a tertiary University hospital in Rome. We included 697 children (0-18 years), with previous SARS-CoV-2 infection. Children and parents were asked questions regarding persistent symptoms of COVID-19. Children with symptoms 30 days after initial diagnosis were 185/697 (26.4%). Moreover, 81/697 (11.6%) patients presented symptoms 90 days after the diagnosis. Thirty-day-persisting symptoms were mostly present in children with anosmia, atopy, asthenia, and cough in the acute phase compared with the asymptomatic children 30 days after infection. After 90 days, symptoms described were mainly neurological (47/697 children, 6.7%), and headache (19/697; 2.7%) was the most frequent manifestation. In conclusion, a relatively large proportion of the patients reported persisting symptoms that seem to be related to the symptom burden and to the atopy. Ninety days after the infection, most of the children had recovered, showing that long-term effects are not frequent. Limitations of the study include the single-center design and the lack of a control group.}, } @article {pmid37754615, year = {2023}, author = {Staples, LG and Nielssen, O and Dear, BF and Bisby, MA and Fisher, A and Kayrouz, R and Titov, N}, title = {Prevalence and Predictors of Long COVID in Patients Accessing a National Digital Mental Health Service.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {18}, pages = {}, pmid = {37754615}, issn = {1660-4601}, mesh = {Adult ; Humans ; Female ; Male ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; Australia/epidemiology ; *Mental Health Services ; Self Report ; }, abstract = {MindSpot is a national mental health service that provides assessments and treatment to Australian adults online or via telephone. Since the start of 2020, questions related to the mental health impacts of COVID-19 have been routinely administered. The objective of the current study is to report the prevalence and predictors of self-reported "long COVID" in patients completing an assessment at the MindSpot Clinic between 5 September 2022 and 7 May 2023 (n = 17,909). Consistent with the World Health Organization definition, we defined long COVID as the occurrence of ongoing physical or mental health symptoms three months after a COVID-19 infection. We conducted a descriptive univariate analysis of patients who reported: no COVID-19 diagnosis (n = 6151); a current or recent (within 3 months) COVID-19 infection (n = 2417); no symptoms three months post-COVID-19 infection (n = 7468); or COVID-related symptoms at least three months post-infection (n = 1873). Multivariate logistic regression was then used to compare patients with and without symptoms three months post-COVID to identify potential predictors for long COVID. The prevalence of long COVID was 10% of the total sample (1873/17909). Patients reporting symptoms associated with long COVID were older, more likely to be female, and more likely to be depressed and report a reduced ability to perform their usual tasks. Sociodemographic factors, including cultural background, education, and employment, were examined. These results provide evidence of the significant prevalence of symptoms of long COVID in people using a national digital mental health service. Reporting outcomes in an Australian context and in specific sub-populations is important for public health planning and for supporting patients.}, } @article {pmid37753372, year = {2023}, author = {Ogarek, N and Oboza, P and Olszanecka-Glinianowicz, M and Kocelak, P}, title = {SARS-CoV-2 infection as a potential risk factor for the development of cancer.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1260776}, pmid = {37753372}, issn = {2296-889X}, abstract = {The COVID-19 pandemic has a significant impact on public health and the estimated number of excess deaths may be more than three times higher than documented in official statistics. Numerous studies have shown an increased risk of severe COVID-19 and death in patients with cancer. In addition, the role of SARS-CoV-2 as a potential risk factor for the development of cancer has been considered. Therefore, in this review, we summarise the available data on the potential effects of SARS-CoV-2 infection on oncogenesis, including but not limited to effects on host signal transduction pathways, immune surveillance, chronic inflammation, oxidative stress, cell cycle dysregulation, potential viral genome integration, epigenetic alterations and genetic mutations, oncolytic effects and reactivation of dormant cancer cells. We also investigated the potential long-term effects and impact of the antiviral therapy used in COVID-19 on cancer development and its progression.}, } @article {pmid37752063, year = {2023}, author = {Han, JH and Jackson, JC and Orun, OM and Brown, SM and Casey, JD and Clark, L and Collins, SP and Cordero, K and Ginde, AA and Gong, MN and Hough, CL and Iwashyna, TJ and Kiehl, AL and Lauck, A and Leither, LM and Lindsell, CJ and Patel, MB and Raman, R and Rice, TW and Ringwood, NJ and Sheppard, KL and Semler, MW and Thompson, BT and Ely, EW and Self, WH and , }, title = {Modifiable in-hospital factors for 12-month global cognition, post-traumatic stress disorder symptoms, and depression symptoms in adults hospitalized with COVID-19.}, journal = {Influenza and other respiratory viruses}, volume = {17}, number = {9}, pages = {e13197}, pmid = {37752063}, issn = {1750-2659}, support = {U01 HL123018/HL/NHLBI NIH HHS/United States ; U01 HL123004/HL/NHLBI NIH HHS/United States ; U01 HL123020/HL/NHLBI NIH HHS/United States ; U01 HL123022/HL/NHLBI NIH HHS/United States ; U01 HL123031/HL/NHLBI NIH HHS/United States ; U01 HL123010/HL/NHLBI NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; U01 HL123008/HL/NHLBI NIH HHS/United States ; U01 HL122989/HL/NHLBI NIH HHS/United States ; U01 HL123033/HL/NHLBI NIH HHS/United States ; R01 AG058639/AG/NIA NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; U01 HL123009/HL/NHLBI NIH HHS/United States ; U01 HL123023/HL/NHLBI NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U01 HL122998/HL/NHLBI NIH HHS/United States ; U01 HL123027/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Adult ; *COVID-19 ; Depression/drug therapy ; Prospective Studies ; *Stress Disorders, Post-Traumatic/drug therapy/epidemiology ; Hospitals ; Cognition ; *Delirium ; }, abstract = {BACKGROUND: We sought to identify potentially modifiable in-hospital factors associated with global cognition, post-traumatic stress disorder (PTSD) symptoms, and depression symptoms at 12 months.

METHODS: This was a multi-center prospective cohort study in adult hospitalized patients with acute COVID-19. The following in-hospital factors were assessed: delirium; frequency of in-person and virtual visits by friends and family; and hydroxychloroquine, corticosteroid, and remdesivir administration. Twelve-month global cognition was characterized by the MOCA-Blind. Twelve-month PTSD and depression were characterized using the PTSD Checklist for the DSM-V and Hospital Anxiety Depression Scale, respectively.

FINDINGS: Two hundred three patients completed the 12-month follow-up assessments. Remdesivir use was associated with significantly higher cognition at 12 months based on the MOCA-Blind (adjusted odds ratio [aOR] = 1.98, 95% CI: 1.06, 3.70). Delirium was associated with worsening 12-month PTSD (aOR = 3.44, 95% CI: 1.89, 6.28) and depression (aOR = 2.18, 95% CI: 1.23, 3.84) symptoms. Multiple virtual visits per day during hospitalization was associated with lower 12-month depression symptoms compared to those with less than daily virtual visits (aOR = 0.40, 95% CI: 0.19, 0.85).

CONCLUSION: Potentially modifiable factors associated with better long-term outcomes included remdesivir use (associated with better cognitive function), avoidance of delirium (associated with less PTSD and depression symptoms), and increased virtual interactions with friends and family (associated with less depression symptoms).}, } @article {pmid37751444, year = {2023}, author = {Shah, AD and Subramanian, A and Lewis, J and Dhalla, S and Ford, E and Haroon, S and Kuan, V and Nirantharakumar, K}, title = {Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0290583}, pmid = {37751444}, issn = {1932-6203}, support = {MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/V033867/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Chest Pain ; Cohort Studies ; *COVID-19/diagnosis/epidemiology ; COVID-19 Testing ; Dyspnea/diagnosis/epidemiology ; Fatigue/diagnosis/epidemiology ; *Post-Acute COVID-19 Syndrome ; Primary Health Care ; Male ; Female ; }, abstract = {BACKGROUND: Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

AIMS: To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

METHODS: We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

RESULTS: We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

CONCLUSIONS: Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.}, } @article {pmid37751413, year = {2024}, author = {Al-Jabr, H and Thompson, DR and Castle, DJ and Ski, CF}, title = {Experiences of people with long COVID: Symptoms, support strategies and the Long COVID Optimal Health Programme (LC-OHP).}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {27}, number = {1}, pages = {e13879}, pmid = {37751413}, issn = {1369-7625}, support = {SIV02/0000555//Mental Health Alliance (East Suffolk, West Suffolk and North East Essex)/ ; }, mesh = {Humans ; *COVID-19/psychology ; Male ; Female ; Middle Aged ; Aged ; Adult ; Post-Acute COVID-19 Syndrome ; Social Support ; Mental Health ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Long COVID (LC) is a multisystem illness, with fluctuating symptoms that affect the daily activities of patients. There are still no standardised diagnostic criteria or treatment approaches for managing LC. The LC-Optimal Health Programme (LC-OHP) was designed to support the mental wellbeing and physical health of people with LC. Gaining an in-depth understanding of patients' experiences and support strategies is imperative to identifying appropriate supports to guide them through their recovery. This study aimed to elicit the experiences and perceptions of adults with LC regarding symptoms, support strategies and the LC-OHP.

METHODS: As part of a wider randomised controlled trial of the LC-OHP, participants in the intervention group had their sessions audio-recorded. Transcripts were thematically analysed to identify common emergent themes.

FINDINGS: The LC-OHP was delivered to 26 participants. Data were collected between January 2022 and February 2023. Four main themes emerged: 'Symptoms and impact of LC'; 'Other sources of support and perceived challenges'; 'Strategies to support LC' and 'Perceptions of the LC-OHP'.

CONCLUSION: LC experiences were mostly described as fluctuating and burdensome that significantly impacted daily activities, and physical and mental health. The LC-OHP was perceived as beneficial. Access and experiences of other sources of support were varied. Increasing LC awareness amongst health practitioners and the wider community has the potential to improve the experiences of those affected by LC.

The LC-OHP was derived from the OHP. It was adapted to people with LC following consultation with practitioners at an LC clinic. Additionally, the mode and timing of delivering the programme to this population were taken into account for its delivery at the convenience of participating patients. While considering that fatigue and brain fog are amongst the most reported complaints of people with LC, public members with LC were not involved directly in this study; however, feedback obtained from practitioners working with this population was implemented in amending the programme and its delivery. Additionally, feedback from patients with other chronic health conditions who used the OHP in previous studies has been implemented to make the programme more user-friendly. Moreover, feedback obtained from participants receiving this programme in this study was implanted immediately and shared with other participants. Finally, this study was overviewed by a data management committee that included two public members with LC, who contributed and provided guidance to support this study.}, } @article {pmid37750203, year = {2023}, author = {Clark, IA and Vissel, B}, title = {Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease.}, journal = {Pharmacology research & perspectives}, volume = {11}, number = {5}, pages = {e01136}, pmid = {37750203}, issn = {2052-1707}, mesh = {Humans ; Chronic Disease ; Cytokines ; Etanercept/pharmacology/therapeutic use ; Microglia ; *Nervous System Diseases/drug therapy ; Tumor Necrosis Factor Inhibitors ; *Tumor Necrosis Factor-alpha/physiology ; Feedback, Physiological ; }, abstract = {Over a decade's experience of post-stroke rehabilitation by administering the specific anti-TNF biological, etanercept, by the novel perispinal route, is consistent with a wide range of chronically diminished neurological function having been caused by persistent excessive cerebral levels of TNF. We propose that this TNF persistence, and cerebral disease chronicity, largely arises from a positive autocrine feedback loop of this cytokine, allowing the persistence of microglial activation caused by the excess TNF that these cells produce. It appears that many of these observations have never been exploited to construct a broad understanding and treatment of certain chronic, yet reversible, neurological illnesses. We propose that this treatment allows these chronically activated microglia to revert to their normal quiescent state, rather than simply neutralizing the direct harmful effects of this cytokine after its release from microglia. Logically, this also applies to the chronic cerebral aspects of various other neurological conditions characterized by activated microglia. These include long COVID, Lyme disease, post-stroke syndromes, traumatic brain injury, chronic traumatic encephalopathy, post-chemotherapy, post-irradiation cerebral dysfunction, cerebral palsy, fetal alcohol syndrome, hepatic encephalopathy, the antinociceptive state of morphine tolerance, and neurogenic pain. In addition, certain psychiatric states, in isolation or as sequelae of infectious diseases such as Lyme disease and long COVID, are candidates for being understood through this approach and treated accordingly. Perispinal etanercept provides the prospect of being able to treat various chronic central nervous system illnesses, whether they are of infectious or non-infectious origin, through reversing excess TNF generation by microglia.}, } @article {pmid37748921, year = {2024}, author = {Høeg, TB and Ladhani, S and Prasad, V}, title = {How methodological pitfalls have created widespread misunderstanding about long COVID.}, journal = {BMJ evidence-based medicine}, volume = {29}, number = {3}, pages = {142-146}, pmid = {37748921}, issn = {2515-4478}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Research Design ; }, } @article {pmid37748518, year = {2024}, author = {Iba, T and Connors, JM and Levy, JH}, title = {What Role Does Microthrombosis Play in Long COVID?.}, journal = {Seminars in thrombosis and hemostasis}, volume = {50}, number = {4}, pages = {527-536}, doi = {10.1055/s-0043-1774795}, pmid = {37748518}, issn = {1098-9064}, mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; *Thrombosis/etiology ; *Post-Acute COVID-19 Syndrome ; Anticoagulants/therapeutic use ; Thromboinflammation ; }, abstract = {Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as "long COVID (postacute sequelae of COVID-19 [PASC])" with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure. Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects. In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.}, } @article {pmid37748514, year = {2023}, author = {Klein, J and Wood, J and Jaycox, JR and Dhodapkar, RM and Lu, P and Gehlhausen, JR and Tabachnikova, A and Greene, K and Tabacof, L and Malik, AA and Silva Monteiro, V and Silva, J and Kamath, K and Zhang, M and Dhal, A and Ott, IM and Valle, G and Peña-Hernández, M and Mao, T and Bhattacharjee, B and Takahashi, T and Lucas, C and Song, E and McCarthy, D and Breyman, E and Tosto-Mancuso, J and Dai, Y and Perotti, E and Akduman, K and Tzeng, TJ and Xu, L and Geraghty, AC and Monje, M and Yildirim, I and Shon, J and Medzhitov, R and Lutchmansingh, D and Possick, JD and Kaminski, N and Omer, SB and Krumholz, HM and Guan, L and Dela Cruz, CS and van Dijk, D and Ring, AM and Putrino, D and Iwasaki, A}, title = {Distinguishing features of long COVID identified through immune profiling.}, journal = {Nature}, volume = {623}, number = {7985}, pages = {139-148}, pmid = {37748514}, issn = {1476-4687}, support = {R01 AI157488/AI/NIAID NIH HHS/United States ; R35 GM143072/GM/NIGMS NIH HHS/United States ; U01 FD005938/FD/FDA HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Antibodies, Viral/blood/immunology ; Biomarkers/blood ; Cross-Sectional Studies ; *Herpesvirus 4, Human/immunology ; *Hydrocortisone/blood ; Immunophenotyping ; *Lymphocytes/immunology ; Machine Learning ; *Myeloid Cells/immunology ; *Post-Acute COVID-19 Syndrome/diagnosis/immunology/physiopathology/virology ; *SARS-CoV-2/immunology ; }, abstract = {Post-acute infection syndromes may develop after acute viral disease[1]. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions[2-4]. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.}, } @article {pmid37748493, year = {2023}, author = {, }, title = {Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {11}, pages = {1003-1019}, pmid = {37748493}, issn = {2213-2619}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; SP/17/16/33519/BHF_/British Heart Foundation/United Kingdom ; MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; MR/S002782/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 209553/WT_/Wellcome Trust/United Kingdom ; FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cohort Studies ; *COVID-19/diagnostic imaging/epidemiology ; Follow-Up Studies ; Hospitalization ; Magnetic Resonance Imaging ; Prospective Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Aged ; }, abstract = {INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures.

METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025.

FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2-6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5-5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4-10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32-4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23-11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation.

INTERPRETATION: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification.

FUNDING: UK Research and Innovation and National Institute for Health Research.}, } @article {pmid37745259, year = {2023}, author = {Bose, P and Chacko, B and Arul, AO and Robinson Vimala, L and Thangakunam, B and Varghese, GM and Jambugulam, M and Lenin, A and Peter, JV}, title = {Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?.}, journal = {World journal of critical care medicine}, volume = {12}, number = {4}, pages = {226-235}, pmid = {37745259}, issn = {2220-3141}, abstract = {BACKGROUND: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction.

AIM: To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders.

METHODS: This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge.

RESULTS: Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%).

CONCLUSION: This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.}, } @article {pmid37745190, year = {2023}, author = {Taruffi, L and Muccioli, L and Bisulli, F}, title = {Neurological Manifestations of Long COVID: A Single-Center One-Year Experience [Response to Letter].}, journal = {Neuropsychiatric disease and treatment}, volume = {19}, number = {}, pages = {1985-1986}, pmid = {37745190}, issn = {1176-6328}, } @article {pmid37745021, year = {2023}, author = {Dagliati, A and Strasser, ZH and Hossein Abad, ZS and Klann, JG and Wagholikar, KB and Mesa, R and Visweswaran, S and Morris, M and Luo, Y and Henderson, DW and Samayamuthu, MJ and Tan, BWQ and Verdy, G and Omenn, GS and Xia, Z and Bellazzi, R and , and Murphy, SN and Holmes, JH and Estiri, H and , }, title = {Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study.}, journal = {EClinicalMedicine}, volume = {64}, number = {}, pages = {102210}, pmid = {37745021}, issn = {2589-5370}, support = {FS/19/52/34563/BHF_/British Heart Foundation/United Kingdom ; P30 ES017885/ES/NIEHS NIH HHS/United States ; R01 AI165535/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning.

METHODS: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes.

FINDINGS: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively.

INTERPRETATION: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems.

FUNDING: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.}, } @article {pmid37744502, year = {2023}, author = {León-Herrera, S and Magallón-Botaya, R and Oliván-Blázquez, B and Sagarra-Romero, L and Jaurrieta, CM and Méndez-López, F}, title = {Online multimodal rehabilitation programme to improve symptoms and quality of life for adults diagnosed with long COVID-19: a Randomised Clinical Trial protocol.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1222888}, pmid = {37744502}, issn = {2296-2565}, mesh = {Humans ; Adult ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19 ; Registries ; Videoconferencing ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Long COVID is a multisystemic condition which affects quality of life and implies a multidisciplinary treatment approach. There is still limited evidence on management techniques for this syndrome. "Telerehabilitation" could be an important tool when addressing the symptoms of this patients with the aim of increasing their quality of life. The purpose of this trial is to analyse the effectiveness of an online multimodal rehabilitation programme to improve the symptomatology of people with long COVID and their quality of life.

METHODS: A pragmatic randomised controlled trial will be performed with two parallel groups: (1) usual treatment by the primary care practitioner (Treatment as usual, TAU; control group) and (2) TAU plus the use of an online multimodal rehabilitation programme, including videoconferences and content published on a Moodle platform (intervention group). The data will be collected before and after the intervention. A follow-up will take place 3 months later.

DISCUSSION: There is still a lack of knowledge regarding the management of the symptoms of long COVID. This creates the need to add scientific evidence about the care of this disease, considering that multidisciplinary social and health teams can offer the necessary care so that these patients can recover their previous quality of life.Clinical trial registration: The protocol for this study was registered with the ISRCTN Registry [registration number: ISRCTN15414370] on 28 December 2022.}, } @article {pmid37744201, year = {2023}, author = {Price, E and Hollis, N and Salganik, J and Lykke, M and Paolinelli, C and Chamovitz, S and King, C and Ott, R}, title = {Implementing a Multidisciplinary Post-COVID Clinic in a Small Community Environment.}, journal = {Archives of rehabilitation research and clinical translation}, volume = {5}, number = {3}, pages = {100270}, pmid = {37744201}, issn = {2590-1095}, abstract = {The emergence of Post-Acute Sequelae of Sars Cov-2 (PASC), also known as long-COVID, has prompted response from the medical community with research in how to treat patient's symptoms, and in some places, development of post-COVID clinics. Publications about PASC clinics thus far have been in large academic research centers, which have access to many specialists, yet only treat a small amount of the US population. Our hospital system was able to develop a multidisciplinary post-COVID clinic in a small rural community using a PM&R (Physical Medicine and Rehabilitation) physician lead, and the ancillary services we had available in our town of 13,508 people. Funding for this was internal with no grant sources. As part of the patient rehabilitation team, the roles of PM&R providers, physical therapy, speech therapy, respiratory therapy, and psychology are portrayed. This developed clinical model is accessible to small communities across the United States.}, } @article {pmid37742748, year = {2023}, author = {Steiner, S and Fehrer, A and Hoheisel, F and Schoening, S and Aschenbrenner, A and Babel, N and Bellmann-Strobl, J and Finke, C and Fluge, Ø and Froehlich, L and Goebel, A and Grande, B and Haas, JP and Hohberger, B and Jason, LA and Komaroff, AL and Lacerda, E and Liebl, M and Maier, A and Mella, O and Nacul, L and Paul, F and Prusty, BK and Puta, C and Riemekasten, G and Ries, W and Rowe, PC and Sawitzki, B and Shoenfeld, Y and Schultze, JL and Seifert, M and Sepúlveda, N and Sotzny, F and Stein, E and Stingl, M and Ufer, F and Veauthier, C and Westermeier, F and Wirth, K and Wolfarth, B and Zalewski, P and Behrends, U and Scheibenbogen, C}, title = {Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité Fatigue Center.}, journal = {Autoimmunity reviews}, volume = {22}, number = {11}, pages = {103452}, doi = {10.1016/j.autrev.2023.103452}, pmid = {37742748}, issn = {1873-0183}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; Prevalence ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.}, } @article {pmid37742147, year = {2023}, author = {Shrestha, DS and Rahat, AM and Sridevi, P and Chalise, BS and Rajbhandari, SK and Bastola, A and Bhandari, P and Ahamed, SI and Love, RR}, title = {A Consecutive Series Study of the Frequencies, Intensities, and Natural History of Symptoms Following COVID-19 Infection in Nepali Men.}, journal = {Journal of Nepal Health Research Council}, volume = {21}, number = {1}, pages = {40-45}, doi = {10.33314/jnhrc.v21i1.4371}, pmid = {37742147}, issn = {1999-6217}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; Nepal/epidemiology ; Documentation ; Exercise ; Family ; }, abstract = {BACKGROUND: In Nepal, approximately one million individuals, two-thirds men, have tested positive for COVID-19. The recovery picture from this infection is undescribed.

METHODS: At one major testing institution in Kathmandu, we attempted to contact men three-four months following documentation of a positive PCR Covid test. If the men contacted consented and reported that they had not completely recovered from their Covid infection, we then sought their answers about the presence and intensities of 23 symptoms.

RESULTS: Of 2043 consecutive test-positive men, we successfully contacted 1254 men/or family members. 14 men had died before our calls, and two reported having cancer or tuberculosis, providing 1238 individuals. 318 (25.7%) reported that they were unrecovered and 311 of these men were successfully interviewed. At a median of 3.5 months from diagnosis, 216 (17.4%) men reported fatigue, 153 (12.4%) pain, 134 (10.8%) difficulty remembering, 133 (10.7%) reduced physical activity, 114 (9.2%) shortness of breath, and 114 (9.2%) poor sleep. By 6 and 9 months, 108 (8.7%) and 55 (4.4%) of men respectively were still unrecovered.

CONCLUSIONS: In this PCR Covid test-positive series of symptomatic men, recovery was significantly prolonged compared with other viral illnesses.}, } @article {pmid37741631, year = {2023}, author = {Hira, R and Baker, JR and Siddiqui, T and Ranada, SI and Soroush, A and Karalasingham, K and Ahmad, H and Mavai, V and Valani, LMA and Ambreen, S and Bourne, KM and Lloyd, MG and Morillo, CA and Sheldon, RS and Raj, SR and , }, title = {Erratum to "Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19" [Can J Cardiol 39 (2023):767-775].}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {11}, pages = {1732}, doi = {10.1016/j.cjca.2023.09.005}, pmid = {37741631}, issn = {1916-7075}, } @article {pmid37741114, year = {2023}, author = {Gouraud, C and Thoreux, P and Ouazana-Vedrines, C and Pitron, V and Betouche, S and Bolloch, K and Caumes, E and Guemouni, S and Xiang, K and Lemogne, C and Ranque, B and , }, title = {Patients with persistent symptoms after COVID-19 attending a multidisciplinary evaluation: Characteristics, medical conclusions, and satisfaction.}, journal = {Journal of psychosomatic research}, volume = {174}, number = {}, pages = {111475}, doi = {10.1016/j.jpsychores.2023.111475}, pmid = {37741114}, issn = {1879-1360}, abstract = {OBJECTIVE: Among patients attending a multidisciplinary day-hospital program for persistent symptoms after COVID-19, we aimed i) to describe their characteristics ii) to present the medical conclusions (diagnoses and recommendations) and iii) to assess the patients' satisfaction and its correlates.

METHODS: For this retrospective chart review study, frequent symptoms were systematically assessed. Standardized questionnaires explored fatigue (Pichot scale), physical activity (Ricci & Gagnon scale), health-related quality of life (Short-Form Health Survey), anxiety and depressive symptoms (Hospital Anxiety and Depression scale) and associated psychological burden (Somatic-Symptom-Disorder B criteria Scale). Medical record conclusions were collected and a satisfaction survey was performed at 3-months follow-up.

RESULTS: Among 286 consecutive patients (median age: 44 years; 70% women), the most frequent symptoms were fatigue (86%), breathlessness (65%), joint/muscular pain (61%) and cognitive dysfunction (58%), with a median duration of 429 days (Inter-quartile range (IqR): 216-624). Questionnaires revealed low levels of physical activity and quality of life, and high levels of fatigue, anxiety, depression, and psychological burden, with 32% and 23% meeting the diagnostic criteria for a depressive or anxiety disorder, respectively. Positive arguments for a functional somatic disorder were found in 76% of patients, including 96% with no abnormal clinical or test findings that may explain the symptoms. Physical activity rehabilitation was recommended for 91% of patients. Patients' median satisfaction was 8/10 (IqR: 6-9).

CONCLUSION: Most patients attending this program presented with long-lasting symptoms and severe quality of life impairment, received a diagnosis of functional somatic disorder, and reported high levels of satisfaction regarding the program.}, } @article {pmid37740918, year = {2023}, author = {, and Alme, TN and Andreasson, A and Asprusten, TT and Bakken, AK and Beadsworth, MB and Boye, B and Brodal, PA and Brodwall, EM and Brurberg, KG and Bugge, I and Chalder, T and Due, R and Eriksen, HR and Fink, PK and Flottorp, SA and Fors, EA and Jensen, BF and Fundingsrud, HP and Garner, P and Havdal, LB and Helgeland, H and Jacobsen, HB and Johnson, GE and Jonsjö, M and Knoop, H and Landmark, L and Launes, G and Lekander, M and Linnros, H and Lindsäter, E and Liira, H and Linnestad, L and Loge, JH and Lyby, PS and Malik, S and Malt, UF and Moe, T and Norlin, AK and Pedersen, M and Pignatiello, SE and Rask, CU and Reme, SE and Roksund, G and Sainio, M and Sharpe, M and Thorkildsen, RF and van Roy, B and Vandvik, PO and Vogt, H and Wyller, HB and Wyller, VBB}, title = {Chronic fatigue syndromes: real illnesses that people can recover from.}, journal = {Scandinavian journal of primary health care}, volume = {41}, number = {4}, pages = {372-376}, pmid = {37740918}, issn = {1502-7724}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/diagnosis/etiology ; }, abstract = {The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.}, } @article {pmid37740629, year = {2023}, author = {Yıldız, Y and Öztürk Şahin, B and Demir, MC and Demir, Ş and Çiftci, B and Köktürk, N and Ulukavak Çiftçi, T and Yurdakul, AS and Yılmaz Demirci, N and Aydoğdu, M and Dizbay, M and Oğuzülgen, İK}, title = {Risk factors for post-acute sequelae of COVID-19 in hospitalized patients: An observational study based on a survey in a tertiary care center in Türkiye.}, journal = {Tuberkuloz ve toraks}, volume = {71}, number = {3}, pages = {261-272}, pmid = {37740629}, issn = {2980-3187}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Aftercare ; Cough/epidemiology/etiology ; Myalgia ; Retrospective Studies ; Tertiary Care Centers ; Patient Discharge ; Disease Progression ; Dyspnea/epidemiology/etiology ; }, abstract = {INTRODUCTION: Long COVID is a multisystem disease with various symptoms and risk factors. We aim to investigate the post-acute sequelae of COVID-19 and related risk factors in a tertiary care center.

MATERIALS AND METHODS: In this observational study, based on a survey of 1.977 COVID-19 patients hospitalized from April 2020 to January 2021, a retrospective assessment was carried out on 1.050 individuals who were reachable via telephone to determine their eligibility for meeting the inclusion criteria.

RESULTS: The data of 256 patients who reported at least one persistent symptom were analyzed. Long COVID prevalence was 24.3%. Among 256 patients (median age 52.8; 52.7% female; 56.63% had at least one comorbidity), dyspnea, fatigue, arthralgia-myalgia, cough, and back pain were the most common post-acute sequelae of COVID-19 (42.4%; 28.29%; 16.33%; 13.15% and 7.17%, respectively). The risk factors for the persistence of dyspnea included having lung diseases such as chronic obstructive pulmonary disease, a history of intensive care support, the requirement for long-term oxygen therapy, and a history of cytokine storm (p= 0.024, p= 0.026, p< 0.001, p= 0.036, p= 0.005, respectively). The correlation between lung involvement with post-discharge cough (p= 0.041) and dizziness (p= 0.038) was significant. No correlation between the symptoms with the severity of acute infection, age, and gender was found. When a multivariate regression analysis was conducted on the most common long COVID-related symptoms, several independent risk factors were identified. These included having lung disease for dyspnea (OR 5.81, 95% CI 1.08-31.07, p= 0.04); length of hospital stay for myalgia (OR 1.034, 95% CI 1.004-1.065, p= 0.024); and pulmonary involvement of over 50% during COVID-19 infection for cough (OR 3.793, 95% CI 1.184-12.147, p= 0.025).

CONCLUSION: COVID-19 survivors will require significant healthcare services due to their prolonged symptoms. We hope that our findings will guide the management of these patients in clinical settings towards best practices.}, } @article {pmid37740628, year = {2023}, author = {Satar, S and Şahin, ME and Ergün, P}, title = {Health related quality of life and its determinants in COVID-19 patients.}, journal = {Tuberkuloz ve toraks}, volume = {71}, number = {3}, pages = {250-260}, pmid = {37740628}, issn = {2980-3187}, mesh = {Humans ; Male ; *Quality of Life ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Inpatients ; Fatigue/epidemiology/etiology ; }, abstract = {INTRODUCTION: One of COVID-19’s limitations is the reduced quality of life (QoL) caused by variety of underlying reasons. Even though multiple papers in the literature reveal a worsening of QoL after COVID-19, there is currently inadequate evidence on which patients’ QoL is impacted the most. Our study’s aim was to determine which patients’ quality of life was most compromised so that interventions for poor QoL should not be overlooked in the post-disease assessments of those in the risk group.

MATERIALS AND METHODS: Patients referred to our pulmonary rehabilitation center for Long COVID symptoms had their dyspnea perception, body composition, exercise capacity, muscle strengths, and psychological state evaluated. In addition, SF-36 was used to assess their QoL. After obtaining all medical data, the patients were separated into three groups based on whether they had the disease as an outpatient, inpatient in the hospital, or in the intensive care unit. The Anova and Kruskal Wallis tests were utilized in the statistical analysis of demographic data among patient groups. Pearson’s test was used for normal distributions, whereas Spearman’s test was used for non-normal distribution analyses. The factors affecting QoL were investigated using multivariate linear regression analysis.

RESULTS: The majority of 173 study participants had poor QoL. Low exercise capacity (p= 0.026), impaired psychosocial status (p= 0.034 for anxiety, p= 0.022 for depression), and increased fatigue (p= 0.001) were the factors affecting SF-36’s physical component summary (PCS), whereas young age (p= 0.026), male sex (p= 0.037), impaired psychosocial status (p< 0.001 for anxiety, p= 0.002 for depression), and increased fatigue (p= 0.005) were the factors affecting the SF-36’s mental component summary (MCS).

CONCLUSION: Young age, male sex, reduced exercise capacity, poor psychosocial status, and increased fatigue are predictors for impaired QoL after COVID19. Therefore, non-medical treatment options that improve QoL should be considered in the follow-up of these patients.}, } @article {pmid37740144, year = {2024}, author = {Owen, R and Ashton, RE and Skipper, L and Phillips, BE and Yates, J and Thomas, C and Ferraro, F and Bewick, T and Haggan, K and Faghy, MA}, title = {Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {1}, pages = {133-143}, pmid = {37740144}, issn = {1573-2649}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Quality of Life/psychology ; *COVID-19/epidemiology ; Mental Health ; United Kingdom ; }, abstract = {PURPOSE: The complexity of long COVID and its diverse symptom profile contributes to unprecedented challenges for patients, clinicians, and healthcare services. The threat of long COVID remains ignored by Governments, the media and public health messaging, and patients' experiences must be heard through understanding of the lived experience. This study aimed to understand the lived experience of those living with long COVID.

METHODS: An online web-based survey was designed using Patient and Public Involvement and Engagement (PPIE) to increase understanding of the lived experiences of long COVID, and was distributed through PPIE groups, social media, and word of mouth. The survey used closed and open questions relating to demographics, pre- and post-COVID-19 health quality of life, daily activities and long COVID experiences.

RESULTS: Within our sample of 132 people living with long COVID, the findings highlight that individuals are being severely impacted by their symptoms and are unable to or limited in participating in their daily activities, reducing quality of life. Long COVID places strain on relationships, the ability to live life fully and is detrimental to mental health. Varying health care experiences are described by participants, with reports of medical gaslighting and inadequate support received.

CONCLUSIONS: Long COVID has a severe impact on the ability to live life fully, and strains mental health. The appropriate mechanisms and support services are needed to support those living with long COVID and manage symptoms.}, } @article {pmid37738512, year = {2024}, author = {Röltgen, K and Boyd, SD}, title = {Antibody and B Cell Responses to SARS-CoV-2 Infection and Vaccination: The End of the Beginning.}, journal = {Annual review of pathology}, volume = {19}, number = {}, pages = {69-97}, doi = {10.1146/annurev-pathmechdis-031521-042754}, pmid = {37738512}, issn = {1553-4014}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; Antibodies ; Vaccination ; }, abstract = {As the COVID-19 pandemic has evolved during the past years, interactions between human immune systems, rapidly mutating and selected SARS-CoV-2 viral variants, and effective vaccines have complicated the landscape of individual immunological histories. Here, we review some key findings for antibody and B cell-mediated immunity, including responses to the highly mutated omicron variants; immunological imprinting and other impacts of successive viral antigenic variant exposures on antibody and B cell memory; responses in secondary lymphoid and mucosal tissues and non-neutralizing antibody-mediated immunity; responses in populations vulnerable to severe disease such as those with cancer, immunodeficiencies, and other comorbidities, as well as populations showing apparent resistance to severe disease such as many African populations; and evidence of antibody involvement in postacute sequelae of infection or long COVID. Despite the initial phase of the pandemic ending, human populations will continue to face challenges presented by this unpredictable virus.}, } @article {pmid37737732, year = {2023}, author = {Rouhana, S and Jacyniak, K and Francis, ME and Falzarano, D and Kelvin, AA and Pyle, WG}, title = {Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {325}, number = {5}, pages = {H1153-H1167}, pmid = {37737732}, issn = {1522-1539}, support = {400358//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; OV5-170349//Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)/ ; VRI-172779//Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)/ ; OV2-170357//Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)/ ; Emerging COVID-19 Research Gaps and Priorities for Vaccines//Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)/ ; Coalition for Epidemic Preparedness Leadership Award in Vaccine Research//Gouvernement du Canada | Canadian Institutes of Health Research (IRSC)/ ; }, mesh = {Female ; Male ; Animals ; Humans ; *COVID-19 ; SARS-CoV-2 ; Ferrets ; Post-Acute COVID-19 Syndrome ; Sex Characteristics ; Sequestosome-1 Protein ; Inflammation ; *Cardiovascular Diseases ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection damages the heart, increasing the risk of adverse cardiovascular events. Female sex protects against complications of infection; females are less likely to experience severe illness or death, although their risk for postacute sequelae of COVID-19 ("long COVID") is higher than in males. Despite the important role of the heart in COVID-19 outcomes, molecular elements in the heart impacted by SARS-CoV-2 are poorly understood. Similarly, the role sex has on the myocardial effects of SARS-CoV-2 infection has not been investigated at a molecular level. We intranasally inoculated female and male ferrets with SARS-CoV-2 and assessed myocardial stress signals, inflammation, and the innate immune response for 14 days. Myocardial phosphorylated GSK3α/β decreased at day 2 postinfection (pi) in male ferrets, whereas females showed no changes. Myocardial levels of p62/SQSTM1 decreased in male ferrets at days 2, 7, and 14 pi while lower baseline levels in females increased on day 2. Phosphorylated ERK1/2 increased in cardiomyocyte nuclei in females on days 2 and 14 pi, whereas male ferrets had no changes. Only hearts from females increased fibrosis on day 14 pi. Immune and inflammation markers increased in hearts, with some sex differences. These results are the first to identify myocardial stress responses following SARS-CoV-2 infection and reveal sex differences that may contribute to differential outcomes. Future research is required to define the pathways involving these stress signals to fully understand the myocardial effects of COVID-19 and identify targets that mitigate cardiac injury following SARS-CoV-2 infection.NEW & NOTEWORTHY Cardiovascular disease is a leading risk factor for severe COVID-19, and cardiovascular pathologies are among the most common adverse outcomes following SARS-CoV-2 infection. Females and males have different outcomes and adverse cardiovascular events following SARS-CoV-2 infection. This study shows sex differences in stress proteins p62/SQSTM1, ERK1/2, and GSK3α/β, along with innate immunity and inflammation in hearts of ferrets infected with SARS-CoV-2, identifying mechanisms of COVID-19 cardiac injury and cardiac complications of long COVID.}, } @article {pmid37737716, year = {2023}, author = {Kim, C and Chen, B and Mohandas, S and Rehman, J and Sherif, ZA and Coombs, K and , and , }, title = {The importance of patient-partnered research in addressing long COVID: Takeaways for biomedical research study design from the RECOVER Initiative's Mechanistic Pathways taskforce.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37737716}, issn = {2050-084X}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Disease Progression ; *Biomedical Research ; }, abstract = {The NIH-funded RECOVER study is collecting clinical data on patients who experience a SARS-CoV-2 infection. As patient representatives of the RECOVER Initiative's Mechanistic Pathways task force, we offer our perspectives on patient motivations for partnering with researchers to obtain results from mechanistic studies. We emphasize the challenges of balancing urgency with scientific rigor. We recognize the importance of such partnerships in addressing post-acute sequelae of SARS-CoV-2 infection (PASC), which includes 'long COVID,' through contrasting objective and subjective narratives. Long COVID's prevalence served as a call to action for patients like us to become actively involved in efforts to understand our condition. Patient-centered and patient-partnered research informs the balance between urgency and robust mechanistic research. Results from collaborating on protocol design, diverse patient inclusion, and awareness of community concerns establish a new precedent in biomedical research study design. With a public health matter as pressing as the long-term complications that can emerge after SARS-CoV-2 infection, considerate and equitable stakeholder involvement is essential to guiding seminal research. Discussions in the RECOVER Mechanistic Pathways task force gave rise to this commentary as well as other review articles on the current scientific understanding of PASC mechanisms.}, } @article {pmid37735654, year = {2023}, author = {Syed, U and Subramanian, A and Wraith, DC and Lord, JM and McGee, K and Ghokale, K and Nirantharakumar, K and Haroon, S}, title = {Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {363}, pmid = {37735654}, issn = {1741-7015}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; /VAC_/Versus Arthritis/United Kingdom ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Incidence ; Cohort Studies ; *Diabetes Mellitus, Type 1 ; Immunomodulating Agents ; Primary Health Care ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).

METHODS: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications.

RESULTS: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42).

CONCLUSIONS: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.}, } @article {pmid37734886, year = {2023}, author = {Messiah, SE and Francis, J and Weerakoon, S and Mathew, MS and Shaikh, S and Veeraswamy, A and Lozano, A and He, W and Xie, L and Polavarapu, D and Ahmed, N and Kahn, J}, title = {Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e069073}, pmid = {37734886}, issn = {2044-6055}, mesh = {Humans ; Adolescent ; Child ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; Fear ; Information Sources ; }, abstract = {OBJECTIVES: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection.

A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo.

RESULTS: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems.

CONCLUSIONS: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities.}, } @article {pmid37733584, year = {2024}, author = {Weissert, R}, title = {Nervous system-related tropism of SARS-CoV-2 and autoimmunity in COVID-19 infection.}, journal = {European journal of immunology}, volume = {54}, number = {1}, pages = {e2250230}, doi = {10.1002/eji.202250230}, pmid = {37733584}, issn = {1521-4141}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Autoimmunity ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; Nervous System ; Tropism ; }, abstract = {The effects of SARS-CoV-2 in COVID-19 on the nervous system are incompletely understood. SARS-CoV-2 can infect endothelial cells, neurons, astrocytes, and oligodendrocytes with consequences for the host. There are indications that infection of these CNS-resident cells may result in long-term effects, including emergence of neurodegenerative diseases. Indirect effects of infection with SARS-CoV-2 relate to the induction of autoimmune disease involving molecular mimicry or/and bystander activation of T- and B cells and emergence of autoantibodies against various self-antigens. Data obtained in preclinical models of coronavirus-induced disease gives important clues for the understanding of nervous system-related assault of SARS-CoV-2. The pathophysiology of long-COVID syndrome and post-COVID syndrome in which autoimmunity and immune dysregulation might be the driving forces are still incompletely understood. A better understanding of nervous-system-related immunity in COVID-19 might support the development of therapeutic approaches. In this review, the current understanding of SARS-CoV-2 tropism for the nervous system, the associated immune responses, and diseases are summarized. The data indicates that there is viral tropism of SARS-CoV-2 in the nervous system resulting in various disease conditions. Prevention of SARS-CoV-2 infection by means of vaccination is currently the best strategy for the prevention of subsequent tissue damage involving the nervous system.}, } @article {pmid37733066, year = {2024}, author = {Thompson, CM and Babu, S and Gerlikovski, E and McGuire, M and Makos, S and Ranallo, A and Robieson, I}, title = {Living with Long COVID: A Longitudinal Interview Study of Individuals' Communicative Resilience Through the "Long Haul".}, journal = {Health communication}, volume = {39}, number = {10}, pages = {2135-2151}, doi = {10.1080/10410236.2023.2257941}, pmid = {37733066}, issn = {1532-7027}, mesh = {Humans ; *COVID-19/psychology/epidemiology ; *Resilience, Psychological ; Longitudinal Studies ; Female ; Male ; Middle Aged ; *Interviews as Topic ; *SARS-CoV-2 ; *Communication ; Aged ; Adult ; Adaptation, Psychological ; Post-Acute COVID-19 Syndrome ; Pandemics ; Qualitative Research ; }, abstract = {It is estimated that there are 65 million people globally - 19 million U.S. adults alone - who have long COVID, or persistent symptoms and conditions that continue or develop after an initial SARS-CoV-2 infection. Amidst their suffering and the ambiguity surrounding their health, people with long COVID engage processes of reintegrating from disruptions brought upon by their COVID-19 infection and its fallout, as well as the pandemic writ large. This process is communicative resilience (Buzzanell, 2010, 2017, 2019), and the purpose of this study is to document the experiences of people with long COVID as they sensemake, adapt, and transform their lives through communication. We employed longitudinal interviewing during the middle stages of the pandemic (Summer 2021 to Summer 2022), talking to 19 people with long COVID over the course of one year (five interviews each; 89 total interviews). Grounded in the six processes of communicative resilience, findings center the temporal and dialectic nature of resilience, with throughlines of grief, patience, and hope set against a tumultuous sociopolitical backdrop. Findings of this study have implications for how resilience is studied across time; how people learn to live with chronic illnesses; and how to support people living with long COVID and those who provide them care.}, } @article {pmid37732865, year = {2022}, author = {Rudenstine, S and Schulder, T and Bhatt, KJ and McNeal, K and Ettman, CK and Galea, S}, title = {Long-COVID and comorbid depression and anxiety two years into the COVID-19 pandemic.}, journal = {Psychiatry research}, volume = {317}, number = {}, pages = {114924}, pmid = {37732865}, issn = {1872-7123}, mesh = {Adult ; Male ; Female ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Depression/epidemiology ; Anxiety/epidemiology ; }, abstract = {Long-COVID, or the persistence of COVID-19 symptoms for months after initial infection, has been shown to impact the lives of those affected. The current study sought to investigate the relationships between long-COVID, COVID-19 related stress, depression, anxiety, and comorbid depression and anxiety outcomes. Data were collected in Winter 2021-2022 from a population of adults enrolled in at least one course across multiple City University of New York (CUNY) campuses. Frequencies and chi-square tests were computed to assess for demographics and relationships to probable diagnoses of depression and anxiety, and binary logistic regressions were computed to assess for the odds of probable comorbid depression and anxiety based on demographics, stressors, and long-COVID. Women participants reported higher odds of probable depression outcomes, and stressor levels were significant correlates of probable anxiety outcomes. Women participants, 3.2 [1.5-6.9], as compared to men, lower-SES participants, 2.16 [1.1-4.2], as compared to higher-SES participants, participants with higher COVID-19 related stress levels, 4.8 [2.0-12.0], as compared to those with low levels, and participants with long-COVID, 3.7 [1.9-7.0], as compared to those without, all had higher odds of probable comorbid depression and anxiety. Findings highlight the importance of social location, stress, and long-COVID, in tandem, as correlates of psychological health during the shifting pandemic.}, } @article {pmid37732339, year = {2023}, author = {Coscia, F and Di Filippo, ES and Gigliotti, PV and Fanò-Illic, G}, title = {Comments on: Effect of physical activity on long COVID fatigue.}, journal = {European journal of translational myology}, volume = {33}, number = {3}, pages = {}, pmid = {37732339}, issn = {2037-7452}, abstract = {The authors of the Comments on: Effect of physical activity on long COVID fatigue by Daungsupawong F. and Wiwanitkit V. (2023) have highlighted certain aspects of future research that need to be considered before any conclusions can be drawn regarding the effect of previous physical activity and/or fitness on the course of long-COVID. We can only agree with this need, although we hope that the effects of SARS-CoV-2 infection will become less and less burdensome to manage. As we hypothesise in the last part of the article by Coscia et al. (2023), we think it is crucial to identify the molecular mechanism underlying the atrophic effect (if any) of the described disease states, which could originate from a local inflammatory storm induced by Spike binding to the ACE-2 receptor in muscle. When studies on muscle from patients will be available in sufficient numbers, we will be able to try to answer the still open questions.}, } @article {pmid37732336, year = {2023}, author = {Lin, M and Cao, K and Xu, F and Wu, X and Shen, Y and Lu, S and Kuang, Z and Ding, H and Yuan, S and Shao, M and Gu, G and Xing, L and Gu, T and Chen, S and Sun, J and Zhu, J and Zhang, X and Yang, Y and Zhao, G and Huang, L and Xu, J and Song, Z}, title = {A follow-up study on the recovery and reinfection of Omicron COVID-19 patients in Shanghai, China.}, journal = {Emerging microbes & infections}, volume = {12}, number = {2}, pages = {2261559}, pmid = {37732336}, issn = {2222-1751}, mesh = {Humans ; *COVID-19 ; Follow-Up Studies ; SARS-CoV-2 ; China/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Reinfection/epidemiology ; Antibodies, Neutralizing ; Antibodies, Viral ; }, abstract = {Limited follow-up data is available on the recovery of Omicron COVID-19 patients after acute illness. It is also critical to understand persistence of neutralizing antibody (NAb) and of T-cell mediated immunity and the role of hybrid immunity in preventing SARS-CoV-2 reinfection. This prospective cohort study included Omicron COVID-19 individuals from April to June 2022 in Shanghai, China, during a large epidemic caused by the Omicron BA.2 variant. A total of 8945 patients from three medical centres were included in the follow up programme from November 2022 to February 2023. Of 6412 individuals enrolled for the long COVID analysis, 605 (9.4%) individuals experienced at least one sequelae, mainly had fatigue and mental symptoms specific to Omicron BA.2 infection compared with other common respiratory tract infections. During the second-visit, 548 (12.1%) cases of Omicron reinfection were identified. Hybrid immunity with full and booster vaccination had reduced risk of SARS-CoV-2 reinfection by 0.29-fold (95% CI: 0.63-0.81) and 0.23-fold (95% CI: 0.68-0.87), respectively. For 469 participants willing to the hospital during the first visit, those who received full (72 [IQR, 36-156]) or booster (64 [IQR, 28-132]) vaccination had significantly higher neutralizing antibody titers than those with incomplete vaccination (36 [IQR, 16-79]). Moreover, non-reinfection cases had higher neutralizing antibody titers (64 [IQR, 28-152]) compared to reinfection cases (32 [IQR, 20-69]).}, } @article {pmid37731516, year = {2023}, author = {Nakagawara, K and Morita, A and Namkoong, H and Terai, H and Chubachi, S and Asakura, T and Tanaka, H and Ito, F and Matsuyama, E and Kaji, M and Saito, A and Takaoka, H and Okada, M and Sunata, K and Watase, M and Yagi, K and Ohgino, K and Miyata, J and Kamata, H and Kawada, I and Kobayashi, K and Hirano, T and Inoue, T and Kagyo, J and Shiomi, T and Otsuka, K and Miyao, N and Odani, T and Baba, R and Arai, D and Nakachi, I and Ueda, S and Funatsu, Y and Koh, H and Ishioka, K and Takahashi, S and Nakamura, M and Sato, T and Hasegawa, N and Kitagawa, Y and Kanai, T and Ishii, M and Fukunaga, K}, title = {Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations.}, journal = {Vaccine: X}, volume = {15}, number = {}, pages = {100381}, pmid = {37731516}, issn = {2590-1362}, abstract = {We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.}, } @article {pmid37731386, year = {2023}, author = {Daungsupawong, H and Wiwanitkit, V}, title = {Comments on: Effect of physical activity on long COVID fatigue.}, journal = {European journal of translational myology}, volume = {33}, number = {3}, pages = {}, pmid = {37731386}, issn = {2037-7452}, abstract = {This correspondence discusses a published article on the effects of physical activity on Long COVID fatigue. Confounding factors are possible and should be acknowledged. When managing Long COVID-19 fatigue, you need to worry about other possible causes of the problem.}, } @article {pmid37731377, year = {2023}, author = {McCarthy, MW}, title = {Paxlovid as a potential treatment for long COVID.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {17}, pages = {1839-1843}, doi = {10.1080/14656566.2023.2262387}, pmid = {37731377}, issn = {1744-7666}, mesh = {Humans ; *Antiviral Agents/therapeutic use ; COVID-19 ; *Post-Acute COVID-19 Syndrome/drug therapy ; Prospective Studies ; Ritonavir/therapeutic use ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health opened enrollment for RECOVER-Vital, a randomized study to evaluate new treatment options for long Coronavirus (long COVID).

AREAS COVERED: The RECOVER Initiative is a $1.15 billion research platform intended to describe, categorize, treat, and prevent long-term symptoms following infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2), the virus that causes Coronavirus (COVID-19). More than 200 symptoms have been associated with long COVID, potentially affecting nearly all body systems, and current estimates suggest that between 7 million and 23 million Americans have developed long COVID. However, there are no approved treatments for this condition.

EXPERT OPINION: The first prospective, randomized study of the RECOVER research initiative, RECOVER-Vital, will evaluate the SARS-CoV-2 antiviral nirmatrelvir/ritonavir (Paxlovid) as a potential treatment for long COVID. This manuscript explores what is known about Paxlovid to treat and prevent long COVID and examines the rationale for addressing this condition with an antiviral agent.}, } @article {pmid37731320, year = {2023}, author = {Easter, QT and Matuck, BF and Warner, BM and Byrd, KM}, title = {Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs.}, journal = {Journal of dental research}, volume = {102}, number = {12}, pages = {1303-1314}, pmid = {37731320}, issn = {1544-0591}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *Microbiota ; Mouth/microbiology ; Bacteria ; Multiomics ; }, abstract = {The human mouth, or oral cavity, is at the crossroads of our external and internal environments, and it is increasingly evident that local colonization of dental, oral, and craniofacial (DOC) tissues and cells by bacteria and viruses may also have systemic effects across myriad diseases and disorders. Better understanding of this phenomenon will require a holistic understanding of host-microbial interactions in both spatiotemporal and biogeographical contexts while also considering person-, organ-, tissue-, cell-, and molecular-level variation. After the acute phase interaction with microbes, the establishment of site-specific reservoirs constitutes an important relationship to understand within the human body; however, despite a preliminary understanding of how viral reservoirs originate and persist across the human body, the landscape of single-cell and spatial multiomic tools has challenged our current understanding of what cells and niches can support microbial reservoirs. The lack of complete understanding impacts research into these relevant topics and implementing precision care for microbial-induced or microbial-influenced diseases. Here, via the lens of acute and chronic microbial infections of the DOC tissues, the goal of this review is to highlight and link the emerging spatiotemporal biogeography of host-viral interactomics at 3 levels: (1) DOC cell types in distinct tissues, (2) DOC-associated microbes, and (3) niche-specific DOC pathologies. Further, we will focus on the impact of postacute infectious syndromes such as long COVID, neurodegenerative disorders, and other underappreciated postviral conditions. We will provide hypotheses about how DOC tissues may play roles systemically in these conditions. Throughout, we will underscore how COVID-19 has catalyzed a new understanding of these biological questions, discuss future directions to study these phenomena, and highlight the utility of noninvasive oral biofluids in screening, monitoring, and intervening to prevent and/or ameliorate human infectious diseases.}, } @article {pmid37730373, year = {2023}, author = {Waters, A}, title = {Long covid: the doctors' lives destroyed by an illness they caught while doing their jobs.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1983}, doi = {10.1136/bmj.p1983}, pmid = {37730373}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37729666, year = {2023}, author = {Huynh, DHT and Nguyen, TST and Nguyen, BAH and Nguyen, QT and Duong, VAT and Lam, ANT and Le, TB and Le, TNN and Tran, AT and Tran, HD and Vo, GV and Nguyen, MN}, title = {Clinical Characteristics and Outcomes of Long COVID-19 Hospitalized Children in Vietnam.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {10}, pages = {e366-e368}, doi = {10.1097/INF.0000000000004015}, pmid = {37729666}, issn = {1532-0987}, mesh = {Humans ; Child ; *Child, Hospitalized ; Post-Acute COVID-19 Syndrome ; Vietnam/epidemiology ; Cross-Sectional Studies ; *COVID-19/epidemiology ; }, abstract = {A cross-sectional study was conducted on 205 pediatric patients, including 150 post-COVID-19 patients and 55 noninfected patients. The study identified 10 common respiratory symptoms in post-COVID-19 patients, with significant differences in clinical symptoms between the 2 groups. Post-COVID-19 pediatric patients had a lower lymphocyte count and a higher rate of pneumonia diagnosis, which can persist for up to 16 weeks after discharge. The study's findings can help monitor and manage the clinical burden of post-COVID-19 symptoms in the pediatric population.}, } @article {pmid37729625, year = {2023}, author = {Wang, J and Liu, R and Ma, H and Zhang, W}, title = {The Pathogenesis of COVID-19-Related Taste Disorder and Treatments.}, journal = {Journal of dental research}, volume = {102}, number = {11}, pages = {1191-1198}, doi = {10.1177/00220345231182926}, pmid = {37729625}, issn = {1544-0591}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Dysgeusia/complications ; Post-Acute COVID-19 Syndrome ; Taste Disorders/etiology ; *Taste Buds ; Taste ; }, abstract = {COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.}, } @article {pmid37727759, year = {2023}, author = {Núñez, I and Gillard, J and Fragoso-Saavedra, S and Feyaerts, D and Islas-Weinstein, L and Gallegos-Guzmán, AA and Valente-García, U and Meyerowitz, J and Kelly, JD and Chen, H and Ganio, E and Benkendorff, A and Flores-Gouyonnet, J and Dammann-Beltrán, P and Heredia-González, JF and Rangel-Gutiérrez, GA and Blish, CA and Nadeau, KC and Nolan, G and Crispín, JC and McIlwain, DR and Gaudillière, B and Valdés-Ferrer, SI}, title = {Longitudinal clinical phenotyping of post COVID condition in Mexican adults recovering from severe COVID-19: a prospective cohort study.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1236702}, pmid = {37727759}, issn = {2296-858X}, abstract = {INTRODUCTION: Few studies have evaluated the presence of Post COVID-19 conditions (PCC) in people from Latin America, a region that has been heavily afflicted by the COVID-19 pandemic. In this study, we describe the frequency, co-occurrence, predictors, and duration of 23 symptoms in a cohort of Mexican patients with PCC.

METHODS: We prospectively enrolled and followed adult patients hospitalized for severe COVID-19 at a tertiary care centre in Mexico City. The incidence of PCC symptoms was determined using questionnaires. Unsupervised clustering of PCC symptom co-occurrence and Kaplan-Meier analyses of symptom persistence were performed. The effect of baseline clinical characteristics was evaluated using Cox regression models and reported with hazard ratios (HR).

RESULTS: We found that amongst 192 patients with PCC, respiratory problems were the most prevalent and commonly co-occurred with functional activity impairment. 56% had ≥5 persistent symptoms. Symptom persistence probability at 360 days 0.78. Prior SARS-CoV-2 vaccination and infection during the Delta variant wave were associated with a shorter duration of PCC. Male sex was associated with a shorter duration of functional activity impairment and respiratory symptoms. Hypertension and diabetes were associated with a longer duration of functional impairment. Previous vaccination accelerated PCC recovery.

DISCUSSION: In our cohort, PCC symptoms were frequent (particularly respiratory and neurocognitive ones) and persistent. Importantly, prior SARS-CoV-2 vaccination resulted in a shorter duration of PCC.}, } @article {pmid37727133, year = {2024}, author = {Franchini, M and Maggi, F and Focosi, D}, title = {ABO blood group-related mechanism of infection of SARS-CoV-2: an overview of systematic reviews.}, journal = {Clinical chemistry and laboratory medicine}, volume = {62}, number = {3}, pages = {396-401}, pmid = {37727133}, issn = {1437-4331}, mesh = {Humans ; *SARS-CoV-2 ; ABO Blood-Group System/genetics ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; }, abstract = {Among the host genetic factors playing a role in the susceptibility to infectious diseases, the ABO blood group system is of utmost importance. Following the first reports in early 2020, the association between ABO blood groups and SARS-CoV-2 infection or COVID-19 severity has been thoroughly investigated. The aim of this narrative review is to provide an overview of systematic reviews regarding the link between ABO blood groups and such risks. The possible molecular mechanisms underlying these associations will also be discussed. ABO blood group has a robust association with susceptibility to infection but not with disease severity, and studies on long COVID anre still missing.Prov.}, } @article {pmid37726611, year = {2022}, author = {Doeblin, P and Jahnke, C and Schneider, M and Al-Tabatabaee, S and Goetze, C and Weiss, KJ and Tanacli, R and Faragli, A and Witt, U and Stehning, C and Seidel, F and Elsanhoury, A and Kühne, T and Tschöpe, C and Pieske, B and Kelle, S}, title = {CMR findings after COVID-19 and after COVID-19-vaccination-same but different?.}, journal = {The international journal of cardiovascular imaging}, volume = {38}, number = {9}, pages = {2057-2071}, pmid = {37726611}, issn = {1875-8312}, mesh = {Humans ; COVID-19 Vaccines/adverse effects ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Predictive Value of Tests ; Magnetic Resonance Spectroscopy ; }, abstract = {Cardiac involvement has been described in varying proportions of patients recovered from COVID-19 and proposed as a potential cause of prolonged symptoms, often described as post-COVID or long COVID syndrome. Recently, cardiac complications have been reported from COVID-19 vaccines as well. We aimed to compare CMR-findings in patients with clinical cardiac symptoms after COVID-19 and after vaccination. From May 2020 to May 2021, we included 104 patients with suspected cardiac involvement after COVID-19 who received a clinically indicated cardiac magnetic resonance (CMR) examination at a high-volume center. The mean time from first positive PCR to CMR was 112 ± 76 days. During their COVID-19 disease, 21% of patients required hospitalization, 17% supplemental oxygen and 7% mechanical ventilation. In 34 (32.7%) of patients, CMR provided a clinically relevant diagnosis: Isolated pericarditis in 10 (9.6%), %), acute myocarditis (both LLC) in 7 (6.7%), possible myocarditis (one LLC) in 5 (4.8%), ischemia in 4 (3.8%), recent infarction in 2 (1.9%), old infarction in 4 (3.8%), dilated cardiomyopathy in 3 (2.9%), hypertrophic cardiomyopathy in 2 (1.9%), aortic stenosis, pleural tumor and mitral valve prolapse each in 1 (1.0%). Between May 2021 and August 2021, we examined an additional 27 patients with suspected cardiac disease after COVID-19 vaccination. Of these, CMR provided at least one diagnosis in 22 (81.5%): Isolated pericarditis in 4 (14.8%), acute myocarditis in 9 (33.3%), possible myocarditis (acute or subsided) in 6 (22.2%), ischemia in 3 (37.5% out of 8 patients with stress test), isolated pericardial effusion (> 10 mm) and non-compaction-cardiomyopathy each in 1 (3.7%). The number of myocarditis diagnoses after COVID-19 was highly dependent on the stringency of the myocarditis criteria applied. When including only cases of matching edema and LGE and excluding findings in the right ventricular insertion site, the number of cases dropped from 7 to 2 while the number of cases after COVID-19 vaccination remained unchanged at 9. While myocarditis is an overall rare side effect after COVID-19 vaccination, it is currently the leading cause of myocarditis in our institution due to the large number of vaccinations applied over the last months. Contrary to myocarditis after vaccination, LGE and edema in myocarditis after COVID-19 often did not match or were confined to the RV-insertion site. Whether these cases truly represent myocarditis or a different pathological entity is to be determined in further studies.}, } @article {pmid37726566, year = {2024}, author = {Shmueli, M and Lendner, I and Ben-Shimol, S}, title = {Effect of the COVID-19 pandemic on the pediatric infectious disease landscape.}, journal = {European journal of pediatrics}, volume = {183}, number = {3}, pages = {1001-1009}, pmid = {37726566}, issn = {1432-1076}, mesh = {Child ; Humans ; *COVID-19/epidemiology ; Pandemics/prevention & control ; *Influenza, Human ; Anti-Bacterial Agents/therapeutic use ; *Antimicrobial Stewardship ; *Influenza Vaccines ; }, abstract = {This narrative review aims to present an overview of the COVID-19 pandemic's effects on the landscape of pediatric infectious diseases. While COVID-19 generally results in mild symptoms and a favorable prognosis in children, the pandemic brought forth significant consequences. These included persistent symptoms among infected children ("long COVID"), a profound transformation in healthcare utilization (notably through the widespread adoption of telemedicine), and the implementation of optimization strategies within healthcare settings. Furthermore, the pandemic resulted in alterations in the circulation patterns of respiratory pathogens, including influenza, RSV, and Streptococcus pneumoniae. The possible reasons for those changes are discussed in this review. COVID-19 effect was not limited to respiratory infectious diseases, as other diseases, including urinary tract and gastrointestinal infections, have displayed decreased transmission rates, likely attributable to heightened hygiene measures and shifts in care-seeking behaviors. Finally, the disruption of routine childhood vaccination programs has resulted in reduced immunization coverage and an upsurge in vaccine hesitancy. In addition, the pandemic was associated with issues of antibiotic misuse and over-prescription. Conclusion: In conclusion, the COVID-19 pandemic has left a profound and multifaceted impact on the landscape of pediatric infectious diseases, ranging from the emergence of "long COVID" in children to significant changes in healthcare delivery, altered circulation patterns of various pathogens, and concerning disruptions in vaccination programs and antibiotic usage. What is Known: • COVID-19 usually presents with mild symptoms in children, although severe and late manifestations are possible. • The pandemic resulted in a dramatically increased use of health care services, as well as alterations in the circulation patterns of respiratory pathogens, decreased rates of other, non-respiratory, infections, disruption of routine childhood vaccination programs, and antibiotic misuse. What is New: • Possible strategies to tackle future outbreaks are presented, including changes in health care services utilization, implementation of updated vaccine programs and antibiotic stewardship protocols. • The decline in RSV and influenza circulation during COVID-19 was probably not primarily related to NPI measures, and rather related to other, non-NPI measures implementation, including specific pathogen-host interactions on the level of the biological niche (the nasopharynx).}, } @article {pmid37726174, year = {2023}, author = {MacLean, A and Wild, C and Hunt, K and Nettleton, S and Skea, ZC and Ziebland, S}, title = {Impact of Long Covid on the school experiences of children and young people: a qualitative study.}, journal = {BMJ open}, volume = {13}, number = {9}, pages = {e075756}, pmid = {37726174}, issn = {2044-6055}, support = {HSRU1/CSO_/Chief Scientist Office/United Kingdom ; HSRU2/CSO_/Chief Scientist Office/United Kingdom ; COV-LT2-0005/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Child ; Female ; Adolescent ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Schools ; *Academic Success ; Educational Status ; }, abstract = {OBJECTIVES: To explore the impact of Long Covid (LC) on the school experiences of children and young people (CYP).

DESIGN: Qualitative study using narrative interviews.

PARTICIPANTS: 22 CYP (aged 10-18 years, 15 female) with LC and 15 parents/caregivers (13 female) of CYP (aged 5-18 years) with LC.

SETTING: Interviews were conducted between October 2021 and July 2022 via online video call or telephone. Recruitment routes included social media, LC support groups, clinicians, community groups and snowballing.

RESULTS: Three key findings were identified. Finding 1: Going to school is a valued part of CYP's lives and participants viewed educational attainment as important for their future trajectories. Returning to school full time was highlighted as a key part of regaining 'normal life'. Finding 2: Attending school (in-person or online) with LC is extremely difficult; even a gradual return required CYP to balance the impact of being at and engaging with school, with the need to manage symptoms to prevent relapse. Often this meant prioritising school and rest over other aspects of their lives. Finding 3: School responses to CYP with LC were reported to be mixed and hampered by difficulties communicating with healthcare professionals during the pandemic and a lack of awareness of LC among healthcare and education professionals. Participants viewed supportive school responses as staff believing, understanding and taking them seriously, alongside schools offering tailored and flexible adaptations which allowed engagement with school while limiting any deterioration of symptoms.

CONCLUSIONS: This study describes how LC affects the school experiences of CYP and generates recommendations for supportive school responses alongside supportive healthcare professionals. Further research could explore the approaches that facilitate a successful return to school for CYP with LC and investigate education professionals' perspectives on support they require to positively engage with returning pupils.}, } @article {pmid37725530, year = {2023}, author = {Effiong, A}, title = {Postacute Sequelae of COVID-19 and Adverse Psychiatric Outcomes: Protocol for an Etiology and Risk Systematic Review.}, journal = {JMIRx med}, volume = {4}, number = {}, pages = {e43880}, pmid = {37725530}, issn = {2563-6316}, abstract = {BACKGROUND: The postacute sequelae of COVID-19 (PASC) is a syndrome characterized by persistent COVID-19 symptoms or the onset of new symptoms following recovery from the initial or acute phase of the illness. Such symptoms often occur 4 or more weeks after being diagnosed with COVID-19. Although a lot of work has gone into understanding the long-term mental health effects of PASC, many questions related to the etiology and risk of this condition remain.

OBJECTIVE: This protocol is for a systematic review assessing the association between PASC and adverse psychiatric outcomes and whether people with PASC are at greater risk of developing an adverse psychiatric outcome than those without PASC.

METHODS: Various medical literature databases (eg, PubMed and EMBASE) will be searched for eligible articles, using predefined search criteria. Gray literature will also be explored. Epidemiological observational studies and secondary analyses of randomized controlled trials that report a quantitative relationship between PASC and at least one adverse psychiatric outcome will be included. The Population, Exposure of interest, Comparator, and Outcome framework will be used as a standardized framework for the inclusion criteria. The Joanna Briggs Institute critical appraisal tools will be used to assess methodological quality and critically appraise the risk of bias in included studies. A random-effects meta-analysis will be conducted if possible. A formal narrative synthesis will be performed if a meta-analysis is impossible due to substantial heterogeneity across studies. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the cumulative certainty of the evidence for all outcomes. Ethical approval is not required. The study results will be published in a peer-reviewed journal.

RESULTS: This study documents and addresses etiology, risk factors, and long-term symptoms of COVID-19 among people with PASC. It focuses on a key priority area for new evidence syntheses on the clinical management of COVID-19 and pandemic-related conditions. It will include evidence on nonhospitalized and hospitalized patients with a history of PASC.

CONCLUSIONS: Substantial heterogeneity across studies may limit the ability to perform a meta-analysis. Findings will inform disease prevention, decision-making, health care policy, and clinical research (Reviewed by the Plan P #PeerRef Community).

TRIAL REGISTRATION: PROSPERO CRD42022308737; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=308737.}, } @article {pmid37725497, year = {2023}, author = {Meagher, T}, title = {Long Covid - Into the Third Year.}, journal = {Journal of insurance medicine (New York, N.Y.)}, volume = {50}, number = {1}, pages = {54-58}, doi = {10.17849/insm-50-1-54-58.1}, pmid = {37725497}, issn = {0743-6661}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Cluster Analysis ; North America ; }, abstract = {As the COVID-19 pandemic reaches the end of its third year, and as COVID-related mortality in North America wanes, long Covid and its disabling symptoms are attracting more attention. Some individuals report symptoms lasting more than 2 years, and a subset report continuing disability. This article will provide an update on long Covid, with a particular focus on disease prevalence, disability, symptom clustering and risk factors. It will also discuss the longer-term outlook for individuals with long Covid.}, } @article {pmid37725480, year = {2023}, author = {Hammel, IS and Tosi, DM and Tang, F and Pott, H and Ruiz, JG}, title = {Frailty as a risk factor for post-acute sequelae of COVID-19 among US veterans during the Delta and Omicron waves.}, journal = {Journal of the American Geriatrics Society}, volume = {71}, number = {12}, pages = {3826-3835}, doi = {10.1111/jgs.18584}, pmid = {37725480}, issn = {1532-5415}, mesh = {Male ; Humans ; Aged ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Frailty/epidemiology ; Retrospective Studies ; *Veterans ; Risk Factors ; Disease Progression ; }, abstract = {BACKGROUND: Older populations have suffered the highest rates of SARS-CoV-2 infection and associated complications, including Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Frailty is a geriatric syndrome that often coexists with COVID-19 infection. The vulnerability to stressors caused by multisystemic dysfunction that characterizes frailty may predispose older adults to develop PASC.

METHODS: Retrospective cohort study using the VA COVID-19 Shared Data Resource to identify US veterans testing positive for SARS-CoV-2 between July 2021 and February 2022, without prior positive tests and who were alive 30 days after infection. Frailty was calculated using a 31-item VA Frailty Index generated from electronic health records. We categorized Veterans into robust (FI ≤ 0.10), prefrail (FI: >0.10- < 0.21), and frail (FI ≥ 0.21). We assessed the association between frailty and PASC and vaccination and PASC using Cox survival model, adjusting for covariates.

RESULTS: We identified 245,857 COVID-19-positive veterans surviving 30 days after infection. The mean age was 57.5 ± 16.5 years; 87.2% were males, 68.1% were white, and 9.0% were Hispanic. Almost half of the sample (48.9%) were classified as robust, while 28.3% were pre-frail and 22.7% were frail; 99,886 (40.6%) were fully vaccinated, and 33,516 (13.6%) received booster doses. Over a median follow-up of 143 days (IQR = 101), 23,890 (9.7%) patients developed PASC. Within 6 months after infection, frailty and pre-frailty were associated with a 41% (adjusted HR [aHR]:1.40 (95% CI: 1.35-1.47) and 15% (aHR: 1.17 (95% CI: 1.11-1.19) increase in the risk of PASC compared with the robust, respectively. Vaccination and booster doses before infection were associated with a 27% (aHR: 0.73 (95% CI: 0.71-0.75) and 33% (aHR: 0.66 (95% CI: 0.63-0.69) reduction in the risk of developing PASC, respectively.

CONCLUSIONS: Frailty was associated with an increased risk of developing PASC. Vaccination was associated with a decreased risk of PASC, further reduced by booster doses. Early recognition of frailty in patients with COVID-19 may assist in the early identification and management of PASC.}, } @article {pmid37725432, year = {2023}, author = {Dolatabadi, E and Moyano, D and Bales, M and Spasojevic, S and Bhambhoria, R and Bhatti, J and Debnath, S and Hoell, N and Li, X and Leng, C and Nanda, S and Saab, J and Sahak, E and Sie, F and Uppal, S and Vadlamudi, NK and Vladimirova, A and Yakimovich, A and Yang, X and Kocak, SA and Cheung, AM}, title = {Using Social Media to Help Understand Patient-Reported Health Outcomes of Post-COVID-19 Condition: Natural Language Processing Approach.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e45767}, pmid = {37725432}, issn = {1438-8871}, mesh = {Humans ; *COVID-19 ; Natural Language Processing ; Reproducibility of Results ; *Social Media ; Fatigue ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND: While scientific knowledge of post-COVID-19 condition (PCC) is growing, there remains significant uncertainty in the definition of the disease, its expected clinical course, and its impact on daily functioning. Social media platforms can generate valuable insights into patient-reported health outcomes as the content is produced at high resolution by patients and caregivers, representing experiences that may be unavailable to most clinicians.

OBJECTIVE: In this study, we aimed to determine the validity and effectiveness of advanced natural language processing approaches built to derive insight into PCC-related patient-reported health outcomes from social media platforms Twitter and Reddit. We extracted PCC-related terms, including symptoms and conditions, and measured their occurrence frequency. We compared the outputs with human annotations and clinical outcomes and tracked symptom and condition term occurrences over time and locations to explore the pipeline's potential as a surveillance tool.

METHODS: We used bidirectional encoder representations from transformers (BERT) models to extract and normalize PCC symptom and condition terms from English posts on Twitter and Reddit. We compared 2 named entity recognition models and implemented a 2-step normalization task to map extracted terms to unique concepts in standardized terminology. The normalization steps were done using a semantic search approach with BERT biencoders. We evaluated the effectiveness of BERT models in extracting the terms using a human-annotated corpus and a proximity-based score. We also compared the validity and reliability of the extracted and normalized terms to a web-based survey with more than 3000 participants from several countries.

RESULTS: UmlsBERT-Clinical had the highest accuracy in predicting entities closest to those extracted by human annotators. Based on our findings, the top 3 most commonly occurring groups of PCC symptom and condition terms were systemic (such as fatigue), neuropsychiatric (such as anxiety and brain fog), and respiratory (such as shortness of breath). In addition, we also found novel symptom and condition terms that had not been categorized in previous studies, such as infection and pain. Regarding the co-occurring symptoms, the pair of fatigue and headaches was among the most co-occurring term pairs across both platforms. Based on the temporal analysis, the neuropsychiatric terms were the most prevalent, followed by the systemic category, on both social media platforms. Our spatial analysis concluded that 42% (10,938/26,247) of the analyzed terms included location information, with the majority coming from the United States, United Kingdom, and Canada.

CONCLUSIONS: The outcome of our social media-derived pipeline is comparable with the results of peer-reviewed articles relevant to PCC symptoms. Overall, this study provides unique insights into patient-reported health outcomes of PCC and valuable information about the patient's journey that can help health care providers anticipate future needs.

RR2-10.1101/2022.12.14.22283419.}, } @article {pmid37725376, year = {2023}, author = {Pouliopoulou, DV and Macdermid, JC and Saunders, E and Peters, S and Brunton, L and Miller, E and Quinn, KL and Pereira, TV and Bobos, P}, title = {Rehabilitation Interventions for Physical Capacity and Quality of Life in Adults With Post-COVID-19 Condition: A Systematic Review and Meta-Analysis.}, journal = {JAMA network open}, volume = {6}, number = {9}, pages = {e2333838}, pmid = {37725376}, issn = {2574-3805}, mesh = {Humans ; Adult ; Female ; Middle Aged ; Male ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Bayes Theorem ; *COVID-19 ; Dyspnea/etiology ; Randomized Controlled Trials as Topic ; }, abstract = {IMPORTANCE: Current rehabilitation guidelines for patients with post-COVID-19 condition (PCC) are primarily based on expert opinions and observational data, and there is an urgent need for evidence-based rehabilitation interventions to support patients with PCC.

OBJECTIVE: To synthesize the findings of existing studies that report on physical capacity (including functional exercise capacity, muscle function, dyspnea, and respiratory function) and quality of life outcomes following rehabilitation interventions in patients with PCC.

DATA SOURCES: A systematic electronic search was performed from January 2020 until February 2023, in MEDLINE, Scopus, CINAHL, and the Clinical Trials Registry. Key terms that were used to identify potentially relevant studies included long-covid, post-covid, sequelae, exercise therapy, rehabilitation, physical activity, physical therapy, and randomized controlled trial.

STUDY SELECTION: This study included randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care, waiting list, or control in patients with PCC.

DATA EXTRACTION AND SYNTHESIS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A pairwise bayesian random-effects meta-analysis was performed using vague prior distributions. Risk of bias was assessed using the Cochrane risk of bias tool version 2, and the certainty of evidence was evaluated using the GRADE system by 2 independent researchers.

MAIN OUTCOMES AND MEASURES: The primary outcome was functional exercise capacity, measured at the closest postintervention time point by the 6-minute walking test. Secondary outcomes were fatigue, lower limb muscle function, dyspnea, respiratory function, and quality of life. All outcomes were defined a priori. Continuous outcomes were reported as standardized mean differences (SMDs) with 95% credible intervals (CrIs) and binary outcomes were summarized as odds ratios with 95% CrIs. The between-trial heterogeneity was quantified using the between-study variance, τ2, and 95% CrIs.

RESULTS: Of 1834 identified records, 1193 were screened, and 14 trials (1244 patients; 45% female participants; median [IQR] age, 50 [47 to 56] years) were included in the analyses. Rehabilitation interventions were associated with improvements in functional exercise capacity (SMD, -0.56; 95% CrI, -0.87 to -0.22) with moderate certainty in 7 trials (389 participants). These improvements had a 99% posterior probability of superiority when compared with current standard care. The value of τ2 (0.04; 95% CrI, 0.00 to 0.60) indicated low statistical heterogeneity. However, there was significant uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% CrI, 0.32 to 9.94).

CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis suggest that rehabilitation interventions are associated with improvements in functional exercise capacity, dyspnea, and quality of life, with a high probability of improvement compared with the current standard care; the certainty of evidence was moderate for functional exercise capacity and quality of life and low for other outcomes. Given the uncertainty surrounding the safety outcomes, additional trials with enhanced monitoring of adverse events are necessary.}, } @article {pmid37724290, year = {2023}, author = {Liang, X and Wang, Q and Liu, J and Ma, J and Zhang, Y and Wang, M and Yu, Y and Wang, L}, title = {Coinfection of SARS-CoV-2 and influenza A (H3N2) detected in bronchoalveolar lavage fluid of a patient with long COVID using metagenomic next-generation sequencing: a case report.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1224794}, pmid = {37724290}, issn = {2235-2988}, mesh = {Humans ; SARS-CoV-2/genetics ; *Coinfection/diagnosis ; *Influenza, Human/diagnosis ; Influenza A Virus, H3N2 Subtype ; Post-Acute COVID-19 Syndrome ; Bronchoalveolar Lavage Fluid ; *COVID-19/diagnosis ; High-Throughput Nucleotide Sequencing ; Dyspnea ; Fatigue ; }, abstract = {The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.}, } @article {pmid37723341, year = {2023}, author = {Altmann, DM and Whettlock, EM and Liu, S and Arachchillage, DJ and Boyton, RJ}, title = {Author Correction: The immunology of long COVID.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {10}, pages = {697}, doi = {10.1038/s41577-023-00948-9}, pmid = {37723341}, issn = {1474-1741}, } @article {pmid37720384, year = {2023}, author = {Li, H and Xia, J and Bennett, D and Roque, F and Bam, RA and Tavares, ABT and Gokhale, M and Ida, F and Rhee, JJ and Soriano Gabarro, M and Song, Y}, title = {Long-COVID-19 clinical and health outcomes: an umbrella review.}, journal = {Therapeutic advances in infectious disease}, volume = {10}, number = {}, pages = {20499361231198335}, pmid = {37720384}, issn = {2049-9361}, abstract = {BACKGROUND: A growing interest in long-term sequelae of COVID-19 has prompted several systematic literature reviews (SLRs) to evaluate long-COVID-19 effects. However, many of these reviews lack in-depth information on the timing, duration, and severity of these conditions.

OBJECTIVES: Our aim was to synthesize both qualitative and quantitative evidence on prevalence and outcomes of long-term effect of COVID-19 through an umbrella review.

DESIGN: Umbrella review of relevant SLRs on long-COVID-19 in terms of prolonged symptoms and clinical conditions, and comprehensively synthesized the latest existing evidence.

DATA SOURCES AND METHODS: We systematically identified and appraised prior systematic reviews/meta-analyses using MEDLINE, Embase, and Cochrane database of systematic review from 2020 to 2021 following the preferred reporting items for systematic reviews and meta-analyses guidance. We summarized and categorized all relevant clinical symptoms and outcomes in adults with COVID-19 using the Medical Dictionary for Regulatory Activities System Organ Class (MedDRA SOC).

RESULTS: We identified 967 systematic reviews/meta-analyses; 36 were retained for final data extraction. The most prevalent SOC were social circumstances (40%), blood and lymphatic system disorders (39%), and metabolism and nutrition disorder (38%). The most frequently reported SOC outcomes within each MedDRA category were poor quality of life (59%), wheezing and dyspnea (19-49%), fatigue (30-64%), chest pain (16%), decreased or loss of appetite (14-17%), abdominal discomfort or digestive disorder (12-18%), arthralgia with or without myalgia (16-24%), paresthesia (27%) and hair loss (14-25%), and hearing loss or tinnitus (15%).

CONCLUSION: This study confirmed a high prevalence of several long COVID-19 outcomes according to the MedDRA categories and indicated that the majority of evidence was rated as moderate to low.

REGISTRATION: The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022303557).}, } @article {pmid37720220, year = {2023}, author = {Ng, CYJ and Bun, HH and Zhao, Y and Zhong, LLD}, title = {TCM "medicine and food homology" in the management of post-COVID disorders.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1234307}, pmid = {37720220}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Public Health ; Food ; Long-Term Care ; World Health Organization ; }, abstract = {BACKGROUND: The World Health Organization declared that COVID-19 is no longer a public health emergency of global concern on May 5, 2023. Post-COVID disorders are, however, becoming more common. Hence, there lies a growing need to develop safe and effective treatment measures to manage post-COVID disorders. Investigating the use of TCM medicinal foods in the long-term therapy of post-COVID illnesses may be beneficial given contemporary research's emphasis on the development of medicinal foods.

SCOPE AND APPROACH: The use of medicinal foods for the long-term treatment of post-COVID disorders is highlighted in this review. Following a discussion of the history of the TCM "Medicine and Food Homology" theory, the pathophysiological effects of post-COVID disorders will be briefly reviewed. An analysis of TCM medicinal foods and their functions in treating post-COVID disorders will then be provided before offering some insight into potential directions for future research and application.

KEY FINDINGS AND DISCUSSION: TCM medicinal foods can manage different aspects of post-COVID disorders. The use of medicinal foods in the long-term management of post-COVID illnesses may be a safe and efficient therapy choice because they are typically milder in nature than chronic drug use. These findings may also be applied in the long-term post-disease treatment of similar respiratory disorders.}, } @article {pmid37719983, year = {2023}, author = {Marques, KC and Quaresma, JAS and Falcão, LFM}, title = {Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1256512}, pmid = {37719983}, issn = {2297-055X}, abstract = {Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.}, } @article {pmid37719518, year = {2023}, author = {Schwartz, B and Moudgil, S and Pollina, F and Bhargava, A}, title = {Small Fiber Neuropathy After SARS-CoV-2 Infection and Vaccination: A Case-Based Comparison.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e43600}, pmid = {37719518}, issn = {2168-8184}, abstract = {COVID-19-associated neuropathies, whether post-infection or post-vaccination, have not been fully described. A variety of theories exist to explain these phenomena, many of them centering on immune dysregulation. We aim to contribute to the discussion on the similarities and differences behind the two conditions and to bolster the call for further research to be done in this area. We will discuss two different case presentations, one patient experiencing a post-COVID-19 infection neuropathy and the other experiencing a post-COVID-19 vaccination neuropathy.}, } @article {pmid37719243, year = {2023}, author = {Oliveira, A and Fabbri, G and Gille, T and Bargagli, E and Duchemann, B and Evans, R and Pinnock, H and Holland, AE and Renzoni, E and Ekström, M and Jones, S and Wijsenbeek, M and Dinh-Xuan, AT and Vagheggini, G}, title = {Holistic management of patients with progressive pulmonary fibrosis.}, journal = {Breathe (Sheffield, England)}, volume = {19}, number = {3}, pages = {230101}, pmid = {37719243}, issn = {1810-6838}, abstract = {UNLABELLED: Progressive pulmonary fibrosis (PF) is a complex interstitial lung disease that impacts substantially on patients' daily lives, requiring personalised and integrated care. We summarise the main needs of patients with PF and their caregivers, and suggest a supportive care approach. Individualised care, education, emotional and psychological support, specialised treatments, and better access to information and resources are necessary. Management should start at diagnosis, be tailored to the patient's needs, and consider end-of-life care. Pharmacological and non-pharmacological interventions should be individualised, including oxygen therapy and pulmonary rehabilitation, with digital healthcare utilised as appropriate. Further research is needed to address technical issues related to oxygen delivery and digital healthcare.

EDUCATIONAL AIMS: To identify the main needs of patients with PF and their caregivers.To describe the components of a comprehensive approach to a supportive care programme for patients with PF.To identify further areas of research to address technical issues related to the management of patients with PF.}, } @article {pmid37718435, year = {2023}, author = {Ruiz-Pablos, M and Paiva, B and Zabaleta, A}, title = {Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {633}, pmid = {37718435}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Herpesvirus 4, Human ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections/complications ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of chronic viral infection, autoimmunity, chronic inflammatory state, viral reactivation, hypocortisolism, and microclot formation. They also present with similar symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, and neurological and gastrointestinal complaints. In addition, both pathologies present Epstein-Barr virus (EBV) reactivation, indicating the possibility of this virus being the link between both pathologies. Therefore, we propose that latency and recurrent EBV reactivation could generate an acquired immunodeficiency syndrome in three steps: first, an acquired EBV immunodeficiency develops in individuals with "weak" EBV HLA-II haplotypes, which prevents the control of latency I cells. Second, ectopic lymphoid structures with EBV latency form in different tissues (including the CNS), promoting inflammatory responses and further impairment of cell-mediated immunity. Finally, immune exhaustion occurs due to chronic exposure to viral antigens, with consolidation of the disease. In the case of LC, prior to the first step, there is the possibility of previous SARS-CoV-2 infection in individuals with "weak" HLA-II haplotypes against this virus and/or EBV.}, } @article {pmid37718186, year = {2023}, author = {Shaver, N and Katz, M and Darko Asamoah, G and Linkins, LA and Abdelkader, W and Beck, A and Bennett, A and Hughes, SE and Smith, M and Begin, M and Coyle, D and Piggott, T and Kagina, BM and Welch, V and Colijn, C and Earn, DJD and El Emam, K and Heffernan, J and O'Brien, SF and Wilson, K and Collins, E and Navarro, T and Beyene, J and Boutron, I and Bowdish, D and Cooper, C and Costa, A and Curran, J and Griffith, L and Hsu, A and Grimshaw, J and Langlois, MA and Li, X and Pham-Huy, A and Raina, P and Rubini, M and Thabane, L and Wang, H and Xu, L and Brouwers, M and Horsley, T and Lavis, J and Iorio, A and Little, J}, title = {Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.}, journal = {Vaccine}, volume = {41}, number = {43}, pages = {6411-6418}, doi = {10.1016/j.vaccine.2023.09.012}, pmid = {37718186}, issn = {1873-2518}, support = {EG9 179477//CIHR/Canada ; }, mesh = {Humans ; Bias ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Meta-Analysis as Topic ; Vaccine Efficacy ; Review Literature as Topic ; }, abstract = {BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2.

METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively.

DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.}, } @article {pmid37717649, year = {2023}, author = {Nayyerabadi, M and Fourcade, L and Joshi, SA and Chandrasekaran, P and Chakravarti, A and Massé, C and Paul, ML and Houle, J and Boubekeur, AM and DuSablon, C and Boudreau, V and Bovan, D and Darbinian, E and Coleman, EA and Vinci, S and Routy, JP and Hétu, PO and Poudrier, J and Falcone, EL}, title = {Vaccination after developing long COVID: Impact on clinical presentation, viral persistence, and immune responses.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {136}, number = {}, pages = {136-145}, doi = {10.1016/j.ijid.2023.09.006}, pmid = {37717649}, issn = {1878-3511}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Prospective Studies ; SARS-CoV-2 ; Vaccination ; Cytokines ; Inflammation ; Immunity ; Chemokines ; }, abstract = {BACKGROUND: Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear.

METHODS: In this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood.

RESULTS: COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P <0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P <0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P <0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination.

CONCLUSIONS: Our study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.}, } @article {pmid37717648, year = {2023}, author = {Chemaitelly, H and Faust, JS and Krumholz, HM and Ayoub, HH and Tang, P and Coyle, P and Yassine, HM and Al Thani, AA and Al-Khatib, HA and Hasan, MR and Al-Kanaani, Z and Al-Kuwari, E and Jeremijenko, A and Kaleeckal, AH and Latif, AN and Shaik, RM and Abdul-Rahim, HF and Nasrallah, GK and Al-Kuwari, MG and Butt, AA and Al-Romaihi, HE and Al-Thani, MH and Al-Khal, A and Bertollini, R and Abu-Raddad, LJ}, title = {Short- and longer-term all-cause mortality among SARS-CoV-2- infected individuals and the pull-forward phenomenon in Qatar: a national cohort study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {136}, number = {}, pages = {81-90}, doi = {10.1016/j.ijid.2023.09.005}, pmid = {37717648}, issn = {1878-3511}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Qatar/epidemiology ; Cohort Studies ; Retrospective Studies ; }, abstract = {OBJECTIVES: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection.

METHODS: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status.

RESULTS: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status.

CONCLUSIONS: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths.}, } @article {pmid37716377, year = {2023}, author = {Liu, TH and Ho, CH and Chen, DT and Wu, JY and Huang, PY and Lai, CC and Hsieh, KY and Su, KP}, title = {Omega-3 polyunsaturated fatty acids and the psychiatric post-acute sequelae of COVID-19: A one-year retrospective cohort analysis of 33,908 patients.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {453-461}, doi = {10.1016/j.bbi.2023.09.008}, pmid = {37716377}, issn = {1090-2139}, abstract = {BACKGROUND: Early prevention and management of psychiatric symptoms in long COVID (or post-COVID-19 conditions) are crucial for reducing long-term disability. Existing clinical guidelines recommend the use of omega-3 polyunsaturated fatty acids (PUFAs) as a promising therapeutic approach for various common psychiatric disorders due to their anti-inflammatory and neuroprotective characteristics. This study aims to investigate the potential efficacy of omega-3 PUFAs in alleviating the psychiatric sequelae following COVID-19.

METHODS: This 1-year retrospective cohort study used the TriNetX electronic health records network to examine the effects of omega-3 PUFAs supplements on psychiatric sequelae in adults diagnosed with COVID-19. Using propensity-score matching, the study compared those who used omega-3 PUFAs supplements with those who did not, assessing outcomes including depression, anxiety disorders, insomnia, and other somatic conditions up to a year after COVID-19 diagnosis.

RESULTS: In 16,962 patients who received omega-3 PUFAs supplements and 2,248,803 who did not, omega-3 supplementation significantly reduced the risk of developing psychiatric sequelae post-COVID-19 diagnosis (HR, 0.804; 95% CI, 0.729 to 0.888). Specifically, the risks for depression (HR, 0.828; 95% CI, 0.714 to 0.960), anxiety disorders (HR, 0.833; 95% CI, 0.743 to 0.933), and insomnia (HR, 0.679; 95% CI, 0.531 to 0.869) were reduced in the omega-3 group. This effect was consistent across sex, race, 18-59 age group, and patients with less than two doses of the COVID-19 vaccine. The omega-3 group also had a lower risk of cough and myalgia, but no significant difference was noted for other symptoms like chest pain, abnormal breathing, abdominal issues, fatigue, headache, and cognitive symptoms.

CONCLUSION: Omega-3 PUFAs may require re-evaluation as a preventive strategy against adverse mental health outcomes post-COVID-19 in placebo-controlled clinical trials.}, } @article {pmid37716352, year = {2023}, author = {Wan, EYF and Mok, AHY and Yan, VKC and Chan, CIY and Wang, B and Lai, FTT and Chui, CSL and Li, X and Wong, CKH and Yiu, KH and Tse, HF and Lau, CS and Wong, ICK and Chan, EWY}, title = {Association between BNT162b2 and CoronaVac vaccination and risk of CVD and mortality after COVID-19 infection: A population-based cohort study.}, journal = {Cell reports. Medicine}, volume = {4}, number = {10}, pages = {101195}, pmid = {37716352}, issn = {2666-3791}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Cardiovascular Diseases/epidemiology ; BNT162 Vaccine ; Cohort Studies ; Retrospective Studies ; *COVID-19/epidemiology/prevention & control ; Vaccination ; }, abstract = {It is unknown if vaccination affects the risk of post-COVID-19 cardiovascular diseases (CVDs). Therefore, this retrospective cohort study examines the short-term and long-term risks of post-infection CVD among COVID-19 patients with different vaccination status utilizing data from electronic health databases in Hong Kong. Cox proportional hazards regression adjusted with inverse probability of treatment weighting is used to evaluate the risks of incident CVD (coronary heart disease, stroke, heart failure) and all-cause mortality in COVID-19 patients. Compared with unvaccinated patients, vaccinated patients have a lower risk of CVD and all-cause mortality, and the lowest risk is observed in those who completed three doses of vaccine. Similar patterns in the subgroups of different vaccine platforms, age, gender, Charlson comorbidity index, and disease severity are observed. These findings highlight a positive dose-response relationship between overall CVD risk reduction and the number of vaccine doses received.}, } @article {pmid37715857, year = {2024}, author = {Faverio, P and Paciocco, G and Tassistro, E and Rebora, P and Rossi, E and Monzani, A and Tundo, M and Milano, C and Messa, M and Marocchi, R and Pesci, A and Foti, G and Squillace, N and Cogliandro, V and Lettino, M and Strepparava, MG and Bellelli, G and Ferrarese, C and Valsecchi, MG and Bonfanti, P and Luppi, F and , }, title = {Two-year cardio-pulmonary follow-up after severe COVID-19: a prospective study.}, journal = {Internal and emergency medicine}, volume = {19}, number = {1}, pages = {183-190}, pmid = {37715857}, issn = {1970-9366}, mesh = {Male ; Humans ; Middle Aged ; Female ; Prospective Studies ; *COVID-19/complications ; Cohort Studies ; Follow-Up Studies ; SARS-CoV-2 ; Dyspnea/etiology ; *Hypertension, Pulmonary ; Disease Progression ; Lung ; }, abstract = {Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.}, } @article {pmid37715729, year = {2023}, author = {Lewthwaite, H and Byrne, A and Brew, B and Gibson, PG}, title = {Treatable traits for long COVID.}, journal = {Respirology (Carlton, Vic.)}, volume = {28}, number = {11}, pages = {1005-1022}, doi = {10.1111/resp.14596}, pmid = {37715729}, issn = {1440-1843}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Chronic Disease ; Fatigue/etiology ; Pain ; }, abstract = {Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.}, } @article {pmid37715721, year = {2024}, author = {Mora, AM and Kogut, K and Sandhu, NK and Ridgway, D and Patty, CM and Renteria, M and Morga, N and Rodriguez, MT and Romero, M and Valdovinos, JM and Torres-Nguyen, A and Guzman, O and Martinez, M and Doty, RL and Padilla, A and Flores, E and Brown, PM and Eskenazi, B and , }, title = {SARS-CoV-2 infection and long COVID among California farmworkers.}, journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association}, volume = {40}, number = {2}, pages = {292-302}, doi = {10.1111/jrh.12796}, pmid = {37715721}, issn = {1748-0361}, support = {//California Public Health Department (CDPH)/ ; //UC Merced Community and Labor Center (CLC)/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Farmers ; SARS-CoV-2 ; California/epidemiology ; }, abstract = {PURPOSE: The purpose of this cross-sectional study was to determine the prevalence of long COVID and identify its clinical manifestations among farmworkers in California.

METHODS: We collected data on sociodemographic characteristics, anthropometrics, clinical chemistries and anti-SARS-CoV-2 immunoglobulin G antibodies, self-reported SARS-CoV-2 infection history, and standardized health tests and scales from 297 farmworkers in California between February and July 2022.

RESULTS: Most participants were born in Mexico or Central America, had less than a high school diploma, and were overweight or obese. The prevalence of long COVID (defined as self-reported SARS-CoV-2 infection with symptoms >28 days) among farmworkers with a suspected or test-confirmed infection was 61.8%. Participants with long COVID had higher mean [95% CI] body mass index (32.9 [31.6-34.1]) and high-sensitivity C-reactive protein levels (4.8 [3.7, 6.0]) than those with no COVID-19 history (30.5 [29.3-31.7], and 3.3 [2.2, 4.3], respectively). Farmworkers with long COVID also reported greater fatigue, dyspnea, taste and smell problems, and overall poorer mental and physical health, than those with no COVID-19 history. Farmworkers with long COVID had increased odds of functional limitations compared to those with a self-reported SARS-CoV-2 infection with symptoms ≤28 days (OR [95% CI]: 7.46 [3.26, 17.09]).

CONCLUSIONS: A significant proportion of farmworkers experience long COVID with persistent symptoms that limit their ability to perform their work. A comprehensive approach that addresses the unique needs and challenges of farmworkers is warranted given this population's high prevalence of long COVID and the essential nature of their work.}, } @article {pmid37714919, year = {2023}, author = {Marjenberg, Z and Leng, S and Tascini, C and Garg, M and Misso, K and El Guerche Seblain, C and Shaikh, N}, title = {Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {15332}, pmid = {37714919}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Quality of Life ; SARS-CoV-2 ; Dyspnea ; Fatigue/etiology ; }, abstract = {This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.}, } @article {pmid37713808, year = {2023}, author = {Sauve, F and Nampoothiri, S and Clarke, SA and Fernandois, D and Ferreira Coêlho, CF and Dewisme, J and Mills, EG and Ternier, G and Cotellessa, L and Iglesias-Garcia, C and Mueller-Fielitz, H and Lebouvier, T and Perbet, R and Florent, V and Baroncini, M and Sharif, A and Ereño-Orbea, J and Mercado-Gómez, M and Palazon, A and Mattot, V and Pasquier, F and Catteau-Jonard, S and Martinez-Chantar, M and Hrabovszky, E and Jourdain, M and Deplanque, D and Morelli, A and Guarnieri, G and Storme, L and Robil, C and Trottein, F and Nogueiras, R and Schwaninger, M and Pigny, P and Poissy, J and Chachlaki, K and Maurage, CA and Giacobini, P and Dhillo, W and Rasika, S and Prevot, V}, title = {Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death.}, journal = {EBioMedicine}, volume = {96}, number = {}, pages = {104784}, pmid = {37713808}, issn = {2352-3964}, support = {810331/ERC_/European Research Council/International ; }, mesh = {Humans ; *Gonadotropin-Releasing Hormone/metabolism ; *COVID-19/psychology/metabolism ; Male ; *Neurons/metabolism ; *Cognitive Dysfunction/etiology/metabolism ; *SARS-CoV-2 ; Aged ; Middle Aged ; Cell Death ; Hypothalamus/metabolism ; Testosterone/metabolism/blood ; Aged, 80 and over ; Brain/metabolism/pathology ; }, abstract = {BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline.

METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue.

FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection.

INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups.

FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR).}, } @article {pmid37712155, year = {2023}, author = {Ambiehl, N and Ambiehl, C and Docquier, L and Jannot, X and Lorenzo-Villalba, N}, title = {[Long COVID, diagnosis and management : a survey among general practitioners in the Bas Rhin in France].}, journal = {Revue medicale de Liege}, volume = {78}, number = {9}, pages = {469-475}, pmid = {37712155}, issn = {0370-629X}, mesh = {Humans ; Female ; Adult ; Male ; Post-Acute COVID-19 Syndrome ; *General Practitioners ; *COVID-19/diagnosis/epidemiology/therapy ; Prospective Studies ; France/epidemiology ; Surveys and Questionnaires ; COVID-19 Testing ; }, abstract = {UNLABELLED: The long COVID includes non-specific symptoms affecting patients of all ages.

METHODS: Monocentric, prospective, quantitative and descriptive study interested in comparing the knowledge of general practitioners in Alsace (France) with the positioning and recommendations of the World Health Organisation (WHO) on long COVID in the period November 2022-February 2023. A multiple-choice questionnaire was elaborated based on the WHO positioning and recommendations on the long COVID.

RESULTS: 126 questionnaires were received, 65 (51.6 %) women, 42 % aged between 25-35 years. 84.9 % had knowledge about long COVID. The need for an impact on daily life, unexplained symptomatology and symptoms persisting at two months were criteria retained (84.9 %, 91.3 % and 82.5 %, respectively). A history of anxiety disorders (86.5 %) and severe acute forms of COVID-19 (57.9 %) were considered as risk factors. Fatigue, dyspnea, joint pain, headache and cough were associated with long COVID in 65.9 % of responders. About 74,6 % performed a complete blood test, 96.03 % recommended rehabilitation, 76.2 % referred to the pulmonologist and 71.4 % were in favour of a consensus document.

CONCLUSIONS: General practitioners are aware of the existence of long COVID as a pathology and agree with the recommendations of scientific societies, among which those of WHO. However, this study has some limitations so that this topic deserves further dedicated investigations.}, } @article {pmid37711562, year = {2023}, author = {Thomaides-Brears, HB and Banerjee, R}, title = {Editorial: Cardiovascular imaging in the integrated assessment of metabolic health.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1276182}, pmid = {37711562}, issn = {2297-055X}, } @article {pmid37711269, year = {2023}, author = {Pearson, L and Maina, A and Compratt, T and Harden, S and Aaroe, A and Copas, W and Thompson, L}, title = {Stellate Ganglion Block Relieves Long COVID-19 Symptoms in 86% of Patients: A Retrospective Cohort Study.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45161}, pmid = {37711269}, issn = {2168-8184}, abstract = {Post-COVID-19 condition, also known as long COVID-19 syndrome and post-acute sequelae of SARS-CoV-2, encompasses an array of symptoms that persist well beyond the initial phase of the viral infection. These symptoms can range in intensity, from mild and manageable to severe and incapacitating. Due to the evolving nature of the SARS-CoV-2 pandemic, treatment protocols for the illness are in a constant state of evolution. The early stage of long COVID-19 syndrome contributes to a dearth of treatment protocols based on empirical evidence, while the absence of a conclusive pathophysiological understanding further complicates the development of such protocols. Current treatment regimens include homeopathic medicine, specialist system-focused treatments, infusion therapies, hyperbaric oxygenation, antivirals, and polypharmacy. The physiological, psychological, and societal impact of long COVID-19 cannot be approached casually and must govern the intensity with which the healthcare community approaches the treatment of long COVID-19 syndrome. In this 41-patient cohort study from a chronic pain management practice, the use of either unilateral or bilateral stellate ganglion block (SGB) was explored to manage symptoms associated with long COVID-19 syndrome. Results indicated that a substantial proportion of patients (86%) experienced a reduction of their symptoms following SGB treatment.}, } @article {pmid37707639, year = {2023}, author = {Martínez-Lavín, M and Miguel-Álvarez, A}, title = {Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model.}, journal = {Clinical rheumatology}, volume = {42}, number = {11}, pages = {3167-3171}, pmid = {37707639}, issn = {1434-9949}, mesh = {Humans ; *Fibromyalgia ; *COVID-19/complications ; *Fatigue Syndrome, Chronic ; *Neuralgia ; Ganglia, Spinal ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is a clear clinical overlap between fibromyalgia, myalgic encephalomyelitis, and post-COVID 19 condition. Chronic fatigue, cognitive impairment, and widespread pain characterize these 3 syndromes. A steady line of investigation posits fibromyalgia as stress-evoked sympathetically maintained neuropathic pain syndrome and places dorsal root ganglia dysregulation with the ensuing small fiber neuropathy at the epicenter of fibromyalgia pathogenesis. This article discusses emerging evidence suggesting that similar mechanism may operate in post-COVID 19 condition.}, } @article {pmid37706263, year = {2023}, author = {Udeh, R and Utrero-Rico, A and Dolja-Gore, X and Rahmati, M and McEVoy, M and Kenna, T}, title = {Lactate dehydrogenase contribution to symptom persistence in long COVID: A pooled analysis.}, journal = {Reviews in medical virology}, volume = {33}, number = {6}, pages = {e2477}, doi = {10.1002/rmv.2477}, pmid = {37706263}, issn = {1099-1654}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; L-Lactate Dehydrogenase ; Plasma ; PubMed ; }, abstract = {There's critical need for risk predictors in long COVID. This meta-analysis evaluates the evidence for an association between plasma lactate dehydrogenase (LDH) and long COVID and explores the contribution of LDH to symptoms persistent across the distinct post-acute sequelae of COVID-19 (PASC) domains. PubMed, EMBASE, Web of Science, and Google Scholar were searched for articles published up to 20 March 2023 for studies that reported data on LDH levels in COVID-19 survivors with and without PASC. Random-effect meta-analysis was employed to estimate the standardized mean difference (SMD) with corresponding 95% confidence interval of each outcome. There were a total of 8289 study participants (3338 PASC vs. 4951 controls) from 46 studies. Our meta-analysis compared to the controls showed a significant association between LDH elevation and Resp-PASC [SMD = 1.07, 95%CI = 0.72, 1.41, p = 0.01] but not Cardio-PASC [SMD = 1.79, 95%CI = -0.02, 3.61, p = 0.05], Neuro-PASC [SMD = 0.19, 95%CI = -0.24, 0.61, p = 0.40], and Gastrointestinal-PASC [SMD = 0.45, 95%CI = -1.08, 1.98, p = 0.56]. This meta-analysis suggests elevated LDH can be used for predicting Resp-PASC, but not Cardio-PASC, Neuro-PASC or gastrointestinal-PASC. Thus, elevated plasma LDH following COVID infection may be considered as a disease biomarker.}, } @article {pmid37705485, year = {2023}, author = {Akbasheva, OE and Mitrofanova, DK and Spirina, LV and Samoilova, YG and Matveeva, MV and Podchinenova, DV and Oleynik, OA}, title = {Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.}, journal = {Biomeditsinskaia khimiia}, volume = {69}, number = {4}, pages = {240-247}, doi = {10.18097/PBMC20236904240}, pmid = {37705485}, issn = {2310-6972}, mesh = {Humans ; *COVID-19 ; Macroglobulins ; Overweight ; Pancreatic Elastase ; Peptide Hydrolases ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; SARS-CoV-2 ; Trypsin ; }, abstract = {The universal proteinase inhibitor α2-macroglobulin (α2-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α2-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α2-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α1-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α2-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α2-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α2-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.}, } @article {pmid37705381, year = {2023}, author = {Kobayashi, M and Ogawa, Y and Sensaki, S and Tanaka, K}, title = {Biopsychosocial approach implications in suspected long COVID: A case report.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {65}, number = {1}, pages = {e15621}, doi = {10.1111/ped.15621}, pmid = {37705381}, issn = {1442-200X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Referral and Consultation ; }, } @article {pmid37705368, year = {2024}, author = {Calcaterra, G and Bassareo, PP and Spaccarotella, CA and Barillà, F and Sciomer, S and Vadalà, G and de Gregorio, C and Romeo, F and Mehta, JL and Mattioli, AV}, title = {The long-term cardiovascular impairment of COVID 19: need for clarity in definition and terminology.}, journal = {Minerva cardiology and angiology}, volume = {72}, number = {1}, pages = {24-31}, doi = {10.23736/S2724-5683.23.06316-0}, pmid = {37705368}, issn = {2724-5772}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; *Cardiovascular System ; *Cardiovascular Diseases/diagnosis/epidemiology ; Disease Progression ; }, abstract = {Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.}, } @article {pmid37704548, year = {2023}, author = {Tran, BT and Cao, R and King, KY}, title = {Over but not gone: lingering epigenetic effects of COVID-19.}, journal = {Trends in immunology}, volume = {44}, number = {10}, pages = {751-753}, pmid = {37704548}, issn = {1471-4981}, support = {R01 AI141716/AI/NIAID NIH HHS/United States ; R35 HL155672/HL/NHLBI NIH HHS/United States ; T32 HL092332/HL/NHLBI NIH HHS/United States ; P01 CA265748/CA/NCI NIH HHS/United States ; F31 HL164287/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/genetics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Epigenesis, Genetic ; }, abstract = {'Long COVID' affects nearly one in five adults who have had coronavirus disease 2019 (COVID-19), yet the mechanisms underlying this disorder remain poorly understood. In a new study, Cheong et al. show that the epigenetic and transcriptional state of myeloid immune cells and their progenitors are durably altered in patients following severe COVID-19.}, } @article {pmid37704072, year = {2025}, author = {Hawley, HB}, title = {Long COVID: Clinical Findings, Pathology, and Endothelial Molecular Mechanisms.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {91-97}, doi = {10.1016/j.amjmed.2023.08.008}, pmid = {37704072}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Endothelium, Vascular/pathology ; Complement Activation ; }, abstract = {Persistence of COVID-19 symptoms may follow severe acute respiratory syndrome coronavirus 2 infection. The incidence of long COVID increases with the severity of acute disease, but even mild disease can be associated with sequelae. The symptoms vary widely, with fatigue, shortness of breath, and cognitive dysfunction the most common. Abnormalities of multiple organs have been documented, and histopathology has revealed widespread microthrombi. Elevated levels of complement are present in acute COVID-19 patients and may persist at lower levels in long COVID. Evidence supports complement activation, with endotheliopathy-associated disease as the molecular mechanism causing both acute and long COVID.}, } @article {pmid37704012, year = {2023}, author = {Hanson, BA and Visvabharathy, L and Orban, ZS and Jimenez, M and Batra, A and Liotta, EM and DeLisle, RK and Klausner, JD and Cohen, P and Padhye, AS and Tachas, G and Koralnik, IJ}, title = {Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {462-474}, pmid = {37704012}, issn = {1090-2139}, support = {K23 AG078705/AG/NIA NIH HHS/United States ; R01 AG069698/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Mitochondrial Proteins ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Proteome ; Proteomics ; Quality of Life ; SARS-CoV-2 ; Disease Progression ; Fatigue ; }, abstract = {Persistent symptoms of COVID-19 survivors constitute long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating, long lasting, and poorly understood. To gain insight into the pathogenesis of PASC, we leveraged a well-characterized group of Neuro-PASC (NP) patients seen at our Neuro-COVID-19 clinic who had mild acute COVID-19 and never required hospitalization to investigate their plasma proteome. Using the SomaLogic platform, SomaScan, the plasma concentration of >7000 proteins was measured from 92 unvaccinated individuals, including 48 NP patients, 20 COVID-19 convalescents (CC) without lingering symptoms, and 24 unexposed healthy controls (HC) to interrogate underlying pathobiology and potential biomarkers of PASC. We analyzed the plasma proteome based on post-COVID-19 status, neurologic and non-neurologic symptoms, as well as subjective and objective standardized tests for changes in quality-of-life (QoL) and cognition associated with Neuro-PASC. The plasma proteome of NP patients differed from CC and HC subjects more substantially than post-COVID-19 groups (NP and CC combined) differed from HC. Proteomic differences in NP patients 3-9 months following acute COVID-19 showed alterations in inflammatory proteins and pathways relative to CC and HC subjects. Proteomic associations with Neuro-PASC symptoms of brain fog and fatigue included changes in markers of DNA repair, oxidative stress, and neutrophil degranulation. Furthermore, we discovered a correlation between NP patients lower subjective impression of recovery to pre-COVID-19 baseline with an increase in the concentration of the oxidative phosphorylation protein COX7A1, which was also associated with neurologic symptoms and fatigue, as well as impairment in QoL and cognitive dysfunction. Finally, we identified other oxidative phosphorylation-associated proteins correlating with central nervous system symptoms. Our results suggest ongoing inflammatory changes and mitochondrial involvement in Neuro-PASC and pave the way for biomarker validation for use in monitoring and development of therapeutic intervention for this debilitating condition.}, } @article {pmid37702769, year = {2023}, author = {Cotugno, N and Amodio, D and Buonsenso, D and Palma, P}, title = {Susceptibility of SARS-CoV2 infection in children.}, journal = {European journal of pediatrics}, volume = {182}, number = {11}, pages = {4851-4857}, pmid = {37702769}, issn = {1432-1076}, support = {PRIN: 2022ZCLC3X//Ministero dell'Università e della Ricerca/ ; 5x1000//Ministero della Salute/ ; }, mesh = {Adult ; *COVID-19/complications ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; SARS-CoV-2 ; *Myocarditis/etiology ; }, abstract = {Coronavirus disease 2019 in children presents with distinct phenotype in comparison to adults. Overall, the pediatric infection with a generally milder clinical course of the acute infection compared to adults still faces several unknown aspects. Specifically, the presence of a wide range of inflammatory manifestations, including multisystem inflammatory syndrome in children (MIS-C), myocarditis, and long COVID in the period after infection suggests a particular susceptibility of some children upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Albeit peculiar complications such as long covid are less frequent in children compared to adults, research on the relationship between inflammatory syndromes and SARS-CoV-2 is rapidly evolving. Conclusions: new studies and findings continue to emerge, providing further insights into the underlying mechanisms and potential therapeutic strategies. In the present work, we revised current knowledge of the main factors accounting for such variability upon SARS-CoV-2 infection over the pediatric age group. What is Known: • COVID19 in children overall showed a milder course compared to adults during the acute phase of the infection. • Children showed to be susceptible to a wide range of post infectious complications including multisystem inflammatory syndrome in children (MIS-C), myocarditis, neuroinflammation, and long COVID. What is New: • Mechanisms underlying susceptibility to a severe course of the infection were recently shown to pertain to the host. • A specific combination of HLA was recently shown to be associated to higher susceptibility to MIS-C in children.}, } @article {pmid37700355, year = {2023}, author = {Brodosi, L and Stecchi, M and Mita, D and Marchignoli, F and Guarneri, V and Agnelli, G and Osti, V and Perazza, F and Sacilotto, F and Pession, A and Pironi, L}, title = {Symptoms of SARS-CoV-2 infection and vaccine status of sixty-seven adult patients affected by inherited metabolic diseases: a phone survey.}, journal = {Orphanet journal of rare diseases}, volume = {18}, number = {1}, pages = {286}, pmid = {37700355}, issn = {1750-1172}, mesh = {Humans ; Adult ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Metabolic Diseases ; Disease Progression ; *Drug-Related Side Effects and Adverse Reactions ; }, abstract = {BACKGROUND: The Covid pandemic seems to have had several detrimental effects on managing patients affected by inherited metabolic diseases (IMD), although published data about the impact of COVID-19 on patients suffering from IMD are very scarce. The scope of our work was to evaluate adherence to the vaccination plan, the side effects experienced by our adult IMD patients, and the symptoms of the SARS-CoV-2 infection.

RESULTS: Sixty-seven patients agreed to respond to a phone interview. The mean age was 36.5 (± 11.6 SD). Regarding the vaccination campaign, fifty-five patients (82%) joined it, of whom ten had received two doses and the remaining forty-five, three. Forty-two patients (76%) reported adverse events following vaccination, the most frequent being local reaction, fever, and asthenia, which lasted an average of two days and resolved without sequelae. Regarding SARS-CoV-2 infection, twenty-seven out of sixty-seven patients (40%) tested positive for the virus; seven of them were not vaccinated at the time of infection; on the other hand, twenty had already had at least two doses. Regarding the prevalence of long-Covid, as many as 12 patients (44%) reported symptoms that persisted after the nasopharyngeal swab tested negative and lasted an average of 81 (± 74 SD) days. There were no statistically significant differences in BMI of patients who contracted the infection and patients who did not (25.15 vs. 25.20, p = .861), between those who had adverse reactions to the vaccine and those who did not (24.40 vs. 25.75, p = .223), between those who had long-Covid and those who did not (25.9 vs. 27.7, p = .183). No relation was observed between metabolic inherited disease, SARS-CoV-2 infection symptoms and adverse vaccine reactions.

CONCLUSIONS: The data indicate that IMD patients adhered to the vaccination campaign comparably to the general Italian population. Adverse events to the vaccine were negligible. SARS-CoV-2 infection, which occurred in most cases after receiving at least two doses of the vaccine, did not cause serious symptoms and never required hospitalisation. A non-negligible share of patients suffered from long-Covid symptoms.}, } @article {pmid37699617, year = {2023}, author = {Rimmer, A}, title = {How can I support my colleague returning to work with long covid?.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1997}, doi = {10.1136/bmj.p1997}, pmid = {37699617}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37698705, year = {2023}, author = {Bode, SFN and Schwender, A and Toth, M and Kaeppler-Schorn, C and Siebeneich, U and Freihorst, J and Janda, A and Fabricius, D}, title = {Characterization of adolescents with functional respiratory disorders and prior history of SARS-CoV-2.}, journal = {Molecular and cellular pediatrics}, volume = {10}, number = {1}, pages = {10}, pmid = {37698705}, issn = {2194-7791}, abstract = {BACKGROUND: The SARS-CoV-2 pandemic has caused significant pulmonary morbidity and mortality in the adult population. Children and adolescents typically show milder symptoms; however, a relevant proportion of them report persistent pulmonary symptoms even after mild SARS-CoV-2 infection. Functional respiratory disorders may be relevant differential diagnoses of persistent dyspnea. This study aims at characterizing functional respiratory disorders that may arise after SARS-CoV-2 infection regarding their clinical presentation and pulmonary function tests as well as gaining insights into the clinical course after initiation of appropriate therapy.

METHODS: This study retrospectively identified all patients referred to an outpatient clinic for pediatric pulmonology with functional respiratory disorders manifesting after proven SARS-CoV-2 infection between January 1, 2022, and October 31, 2022. Clinical history, thorough clinical examination regarding breathing patterns, and pulmonary function tests (PFTs) were taken into consideration to diagnose functional respiratory disorders.

RESULTS: Twenty-five patients (44% female) with mean (m) age = 12.73 years (SD ± 1.86) who showed distinctive features of functional respiratory disorders after SARS-CoV-2 infection (onset at m = 4.15 (± 4.24) weeks after infection) were identified. Eleven patients showed thoracic dominant breathing with insufficient ventilation, and 4 patients mainly had symptoms of inducible laryngeal obstruction. The rest (n = 10) showed overlap of these two etiologies. Most patients had a flattened inspiratory curve on spirometry and slightly elevated residual volume on body plethysmography, but values of PFTs were normal before and after standardized treadmill exercise testing. Patients were educated about the benign nature of the condition and were offered rebreathing training. All patients with follow-up (n = 5) showed normalization of the breathing pattern within 3 months.

CONCLUSIONS: Functional respiratory disorders are important differential diagnoses in persisting post-SARS-CoV-2 dyspnea in adolescents. A combination of clinical history, detailed examination of breathing patterns, and pulmonary function tests are helpful to correctly diagnose these conditions. Reassurance and rebreathing training are the mainstay of the therapy. The clinical course is favorable.}, } @article {pmid37698524, year = {2023}, author = {Baig, AM and Gerlach, J}, title = {Intranasal Route: A Nasocerebral Approach against SARS-CoV-2 in NeuroCOVID.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {19}, pages = {3560-3563}, doi = {10.1021/acschemneuro.3c00488}, pmid = {37698524}, issn = {1948-7193}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Brain ; Nasal Cavity ; }, abstract = {The nasal cavity is a prime site for viral load of SARS-CoV-2 in COVID-19, as is evident from the fact that this area has been used for sample collection for the diagnosis of COVID-19. The nasal cavity has a connection with the brain across the cribriform plate which has been reported to be a route of SARS-CoV-2 to the olfactory apparatus and the brain. Targeting the SARS-CoV-2 in the nasal cavity in patients presenting with COVID-19 and long-COVID can result in the prevention and treatment of neurological deficits and therefore needs to be prioritized as a route of potential significance.}, } @article {pmid37698148, year = {2024}, author = {Tracy, MF and Hagstrom, S and Mathiason, M and Wente, S and Lindquist, R}, title = {Emotional, mental health and physical symptom experience of patients hospitalized with COVID-19 up to 3 months post-hospitalization: A longitudinal study.}, journal = {Journal of clinical nursing}, volume = {33}, number = {2}, pages = {591-605}, doi = {10.1111/jocn.16880}, pmid = {37698148}, issn = {1365-2702}, support = {UL1TR002494/TR/NCATS NIH HHS/United States ; UL1TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; Male ; Female ; *COVID-19/epidemiology ; Mental Health ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Aftercare ; Depression/psychology ; Patient Discharge ; Hospitalization ; Fatigue/epidemiology ; }, abstract = {AIMS AND OBJECTIVES: To explore emotional, mental health and physical symptoms up to 3 months after discharge for adults hospitalized with COVID-19.

BACKGROUND: 10%-30% of adults with COVID-19 experience physical and psychological symptoms 3 months or more following infection. Knowing symptoms can help direct early intervention.

DESIGN: A longitudinal descriptive design to study COVID-related symptoms 2 weeks, 6 weeks and 3 months after hospitalization.

METHODS: Sixty-six patients were recruited from a hospital system in Midwestern US (October 2020-May 2021). Participants self-reported demographics, hospital and post discharge symptoms, PROMIS measures (depression, anxiety, fatigue, cognitive function, satisfaction social roles, sleep disturbance) and Impact of Event Scale-Revised (IES-R). Hospital length of stay, comorbidities, lowest oxygen saturation, respiratory support and resources used were collected. Descriptive and nonparametric statistics described the sample and identified correlations between variables. The STROBE checklist was used.

RESULTS: Data from 1 (T1) and 3 months (T2) post discharge were analysed (N = 52). A majority were female, white and married; 96% experienced ≥1 COVID-related symptoms at T1; 85% at T2. Fatigue was most prevalent, followed by shortness of breath, muscle weakness and foggy thinking. More physical symptoms during hospitalization correlated positively with number of symptoms at T1 and T2; a majority stated these impacted their normal routine 'somewhat' or 'a lot'. T1 depression highly correlated with all T2 PROMIS and IES-R scores and number of physical symptoms. More symptoms at T1 were associated with worse fatigue, lower cognitive function and lower satisfaction with social roles at T2.

CONCLUSION: This study adds to the growing knowledge of mental, physical and emotional symptoms and relationships between these early after hospitalization with COVID-19.

Findings can help identify holistic nursing interventions to improve health and mitigate symptoms for people with long COVID.

Patients contributed via study participation.}, } @article {pmid37698062, year = {2023}, author = {Hansen, KS and Jørgensen, SE and Skouboe, MK and Agergaard, J and Schiøttz-Christensen, B and Vibholm, LK and Tolstrup, M and Østergaard, L and Leth, S and Mogensen, TH}, title = {Examination of autoantibodies to type I interferon in patients suffering from long COVID.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29089}, doi = {10.1002/jmv.29089}, pmid = {37698062}, issn = {1096-9071}, mesh = {Adult ; Male ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; Autoantibodies ; *Interferon Type I ; }, abstract = {Long COVID (LC) is an emerging global health concern. The underlying mechanism and pathophysiology remain unclear. Presence of neutralizing autoantibodies against type 1 interferons (IFN) has been established as a predictor of critical COVID-19. We hypothesized that persistent autoimmune activity with autoantibodies against type 1 IFN may contribute to symptoms in patients with LC. Plasma samples and clinical information were obtained from a Danish LC cohort consisting of adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Information on symptoms and quality of life was derived from an LC-specific questionnaire and the EQ-5D-5L questionnaire. Detection of type 1 IFN autoantibodies in plasma were performed by ELISA. Samples collected between June, 2020, and September, 2021, from 279 patients were analyzed and compared to a control group of 94 individuals with prior mild SARS-CoV-2 infection who did not develop LC symptoms. In total, five LC patients (1.8%) and 3 (3.2%) of the controls had detectable circulating type 1 IFN autoantibodies. Collectively, prevalence of autoantibodies against type 1 IFN subtypes in our LC cohort were primarily driven by men and did not exceed the prevalence in controls. Thus, in our cohort, anti-type I IFN autoantibodies are unlikely to drive LC symptoms.}, } @article {pmid37697012, year = {2024}, author = {Kiyak, C and Ijezie, OA and Ackah, JA and Armstrong, M and Cowen, J and Cetinkaya, D and Burianová, H and Akudjedu, TN}, title = {Topographical Distribution of Neuroanatomical Abnormalities Following COVID-19 Invasion : A Systematic Literature Review.}, journal = {Clinical neuroradiology}, volume = {34}, number = {1}, pages = {13-31}, pmid = {37697012}, issn = {1869-1447}, support = {(2021/22) Quality-Related (QR) Fund//Bournemouth University/ ; }, mesh = {Humans ; Brain/diagnostic imaging/pathology ; *COVID-19/diagnostic imaging/complications ; *Neuroimaging ; SARS-CoV-2 ; }, abstract = {PURPOSE: This systematic review is aimed at synthesising the literature base to date on the frequency and topographical distribution of neuroanatomical changes seen on imaging following COVID-19 invasion with a focus on both the acute and chronic phases of the disease.

METHODS: In this study, 8 databases were systematically searched to identify relevant articles published from December 2019 to March 2022 and supplemented with a manual reference search. Data were extracted from the included studies and narrative synthesis was employed to integrate the findings.

RESULTS: A total of 110 studies met the inclusion criteria and comprised 119,307 participants (including 31,073 acute and 143 long COVID-19 patients manifesting neurological alterations) and controls. Considerable variability in both the localisation and nature of neuroanatomical abnormalities are noted along the continuum with a wide range of neuropathologies relating to the cerebrovascular/neurovascular system, (sub)cortical structures (including deep grey and white matter structures), brainstem, and predominant regional and/or global alterations in the cerebellum with varying degrees of spinal involvement.

CONCLUSION: Structural regional alterations on neuroimaging are frequently demonstrated in both the acute and chronic phases of SARS-CoV‑2 infection, particularly prevalent across subcortical, prefrontal/frontal and cortico-limbic brain areas as well as the cerebrovascular/neurovascular system. These findings contribute to our understanding of the acute and chronic effects of the virus on the nervous system and has the potential to provide information on acute and long-term treatment and neurorehabilitation decisions.}, } @article {pmid37696788, year = {2024}, author = {Howard, J and Cloeren, M and Vanichkachorn, G}, title = {Long COVID and Occupational Medicine Practice.}, journal = {Journal of occupational and environmental medicine}, volume = {66}, number = {1}, pages = {1-5}, pmid = {37696788}, issn = {1536-5948}, mesh = {Humans ; *Occupational Medicine ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; }, } @article {pmid37695426, year = {2023}, author = {Shapiro, JR and Roberts, CW and Arcovio, K and Reade, L and Klein, SL and Dhakal, S}, title = {Effects of Biological Sex and Pregnancy on SARS-CoV-2 Pathogenesis and Vaccine Outcomes.}, journal = {Current topics in microbiology and immunology}, volume = {441}, number = {}, pages = {75-110}, pmid = {37695426}, issn = {0070-217X}, mesh = {Pregnancy ; Humans ; Female ; Male ; SARS-CoV-2/genetics ; *COVID-19/prevention & control ; *Vaccines ; Vaccination ; Virus Internalization ; }, abstract = {SARS-CoV-2 is the causative agent of COVID-19 in humans and has resulted in the death of millions of people worldwide. Similar numbers of infections have been documented in males and females; males, however, are more likely than females to be hospitalized, require intensive care unit, or die from COVID-19. The mechanisms that account for this are multi-factorial and are likely to include differential expression of ACE2 and TMPRSS2 molecules that are required for viral entry into hosts cells and sex differences in the immune response, which are due to modulation of cellular functions by sex hormones and differences in chromosomal gene expression. Furthermore, as comorbidities are also associated with poorer outcomes to SARS-CoV-2 infection and several comorbidities are overrepresented in males, these are also likely to contribute to the observed sex differences. Despite their relative better prognosis following infection with SARS-CoV-2, females do have poorer outcomes during pregnancy. This is likely to be due to pregnancy-induced changes in the immune system that adversely affect viral immunity and disruption of the renin-angiotensin system. Importantly, vaccination reduces the severity of disease in males and females, including pregnant females, and there is no evidence that vaccination has any adverse effects on the outcomes of pregnancy.}, } @article {pmid37694571, year = {2024}, author = {Kempuraj, D and Aenlle, KK and Cohen, J and Mathew, A and Isler, D and Pangeni, RP and Nathanson, L and Theoharides, TC and Klimas, NG}, title = {COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions.}, journal = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, volume = {30}, number = {4}, pages = {421-439}, doi = {10.1177/10738584231194927}, pmid = {37694571}, issn = {1089-4098}, mesh = {*COVID-19 ; Humans ; *Blood-Brain Barrier/virology/pathology/metabolism ; *Tight Junctions/metabolism/virology ; *SARS-CoV-2 ; Brain/virology/pathology ; Betacoronavirus ; Pandemics ; Coronavirus Infections ; Endothelial Cells/virology/metabolism/pathology ; Angiotensin-Converting Enzyme 2/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor-associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.}, } @article {pmid37694114, year = {2023}, author = {Ciurleo, GCV and Tavares-Júnior, JWL and Vieira, CMAG and Braga-Neto, P and Oriá, RB}, title = {Do APOE4 and long COVID-19 increase the risk for neurodegenerative diseases in adverse environments and poverty?.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1229073}, pmid = {37694114}, issn = {1662-4548}, } @article {pmid37693623, year = {2023}, author = {Zhou, T and Sawano, M and Arun, AS and Caraballo, C and Michelsen, T and McAlpine, L and Bhattacharjee, B and Lu, Y and Khera, R and Huang, C and Warner, F and Iwasaki, A and Krumholz, HM}, title = {Internal tremors and vibrations in long COVID: a cross-sectional study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.06.19.23291598}, pmid = {37693623}, support = {T35 HL007649/HL/NHLBI NIH HHS/United States ; }, abstract = {IMPORTANCE: Internal tremors and vibrations symptoms have been described as part of neurologic disorders but not fully described as a part of long COVID.

OBJECTIVE: To compare demographics, socioeconomic characteristics, pre-pandemic comorbidities, new-onset conditions, and long COVID symptoms between people with internal tremors and vibrations as part of their long COVID symptoms and people with long COVID but without these symptoms.

DESIGN: A cross-sectional study, Listen to Immune, Symptom and Treatment Experiences Now (LISTEN), of adults with and without long COVID and post-vaccination syndrome, defined by self-report.

SETTING: Hugo Health Kindred, a decentralized digital research platform hosting a network of English-speaking adults interested in contributing to COVID-related research. No geographic limitation applied.

PARTICIPANTS: The study population included 423 participants who enrolled in LISTEN between May 2022 and June 2023, completed the initial and the conditions and symptoms surveys, reported long COVID, and did not report post-vaccination syndrome.

EXPOSURE: Long COVID symptoms of internal tremors and vibrations.

MAIN OUTCOMES AND MEASURES: Demographics, pre-pandemic comorbidities, and current conditions, other symptoms, and quality of life at the time of surveys.

RESULTS: Of the 423 participants (median age, 46 years [IQR, 38-56]), 74% were female, 87% were Non-Hispanic White, 92% lived in the United States, 46% were infected before the Delta wave, and 158 (37%) reported "internal tremors, or buzzing/vibration" as a long COVID symptom. Before long COVID, the groups had similar comorbidities. Participants with internal tremors were different from others in having worse health as measured by the Euro-QoL visual analogue scale (median: 40 points [IQR, 30-60] vs. 50 points [IQR, 35-62], P = 0.007), having financial difficulties caused by the pandemic (very much financial difficulties, 22% [95% CI, 16-30] vs. 11% [7.3-15], P < 0.001), often feeling socially isolated (43% [95% CI, 35-52] vs. 37% [31-43], P = 0.039), and having higher rates of self-reported new-onset mast cell disorders (11% [95% CI, 7.1-18] vs. 2.6% [1.2-5.6], Bonferroni-adjusted P = 0.008) and neurologic conditions (including but not limited to seizures, dementia, multiple sclerosis, Parkinson's disease, neuropathy, etc.; 22% [95% CI, 16-29] vs. 8.3% [5.4-12], Bonferroni-adjusted P = 0.004).

CONCLUSIONS AND RELEVANCE: Among people with long COVID, those with internal tremors and vibrations have several other associated symptoms and worse health status, despite having similar pre-pandemic comorbidities, suggesting it may reflect a severe phenotype of long COVID.

KEY POINTS: Question: Do people with long COVID symptoms of internal tremors and vibrations differ from others with long COVID but without these symptoms?Findings: In this cross-sectional study that included 423 adults with long COVID, 158 (37%) reported having "internal tremors, or buzzing/vibration," had worse quality of life, more financial difficulties, and higher rates of new-onset mast cell disorders and neurologic conditions, compared with others with long COVID but without internal tremors and vibrations.Meaning: Internal tremors and vibrations may reflect a severe phenotype of long COVID.}, } @article {pmid37691950, year = {2023}, author = {Visvabharathy, L and Hanson, BA and Orban, ZS and Lim, PH and Palacio, NM and Jimenez, M and Clark, JR and Graham, EL and Liotta, EM and Tachas, G and Penaloza-MacMaster, P and Koralnik, IJ}, title = {Corrigendum: Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARSCoV-2 Nucleocapsid protein.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1275925}, doi = {10.3389/fimmu.2023.1275925}, pmid = {37691950}, issn = {1664-3224}, abstract = {[This corrects the article DOI: 10.3389/fimmu.2023.1155770.].}, } @article {pmid37691104, year = {2023}, author = {Cherrez-Ojeda, I and Osorio, MF and Robles-Velasco, K and Calderón, JC and Cortés-Télles, A and Zambrano, J and Guarderas, C and Intriago, B and Gochicoa-Rangel, L}, title = {Small airway disease in post-acute COVID-19 syndrome, a non-conventional approach in three years follow-up of a patient with long COVID: a case report.}, journal = {Journal of medical case reports}, volume = {17}, number = {1}, pages = {386}, pmid = {37691104}, issn = {1752-1947}, support = {2022-MED-002//Universidad de Especialidades Espíritu Santo/ ; }, mesh = {Pulmonary Disease, Chronic Obstructive ; *Asthma ; Humans ; Fatigue ; Follow-Up Studies ; Dyspnea/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Middle Aged ; }, abstract = {BACKGROUND: Small airways disease (SAD), a novel finding described in post-acute COVID-19 patients, should be suspected when respiratory symptoms continue, air trapping persists on expiratory CT scans, and imaging findings fail to improve despite objectively better conventional pulmonary function test (PFT) parameters. The forced oscillation technique (FOT) and Multiple breathing washout (MBW) are both very sensitive methods for detecting anomalies in the peripheral airways.

CASE PRESENTATION: We discuss the case of a 60-year-old Hispanic patient who had severe COVID-19 pneumonia and developed dyspnea, fatigue, and limited daily activity a year later. The PFTs revealed restrictive lung disease, as seen by significant diffusing capacity of the lungs for carbon monoxide (DLCO) decrease, severe desaturation, and poor 6-min walk test (6MWT) performance. The patient was treated with lowering corticosteroids as well as pulmonary rehabilitation (PR). During the 24-month follow-up, the dyspnea and fatigue persisted. On PFTs, 6MWT performance and restricted pattern improved slightly, but MBW discovered significant ventilatory inhomogeneity. FOT revealed substantial peripheral airway obstructive abnormalities. On CT scans, air trapping and ground-glass opacities (GGO) improved somewhat. The patient used a bronchodilator twice a day and low-dose inhaled corticosteroids (160 µg of budesonide and 4.5 µg of formoterol fumarate dihydrate) for nine months. PR sessions were resuming. The restricting parameters were stabilized and the DLCO had normalized after 36 months, with a 6MWT performance of 87% but significant desaturation. The CT scan revealed traction bronchiectasis, low GGO, and persistent air trapping. Without normalization, FOT and MBW scores improved, indicating small airway disease.

CONCLUSIONS: The necessity of integrating these tests when detecting SAD is emphasized in our paper. This article lays the foundation for future research into the best ways to manage and monitor SAD in post-acute COVID-19 patients.}, } @article {pmid37690503, year = {2023}, author = {Lau, B and Wentz, E and Ni, Z and Yenokyan, K and Vergara, C and Mehta, SH and Duggal, P}, title = {Physical Health and Mental Fatigue Disability Associated with Long COVID: Baseline Results from a US Nationwide Cohort.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, pmid = {37690503}, issn = {1555-7162}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Persistent symptoms after severe acute respiratory disease coronavirus 2 (SARS-COV-2; long COVID) occur in 10%-55% of individuals, but the impact on daily functioning and disability remains unquantified.

METHODS: To characterize disability associated with long COVID, we analyzed baseline data from an online, US-based cohort study. Adult participants included those reporting a history of COVID-19 (n = 8874) or never having COVID-19 (n = 633) without prior disability. The main outcomes were self-reported physical mobility, instrumental activities of daily living (IADL), and mental fatigue disability, assessed by measuring 5 disability components: difficulty walking a quarter mile or climbing 10 stairs (mobility), difficulty doing light or heavy housework (IADL), and Wood Mental Fatigue Inventory score (mental fatigue).

RESULTS: Of 7926 participants with long COVID, 65% were classified with at least one disability, as compared with 6% and 14% for resolved COVID and no COVID, respectively. Additionally, 22% were classified as disabled in all 3 categories. Age, prior comorbidity, increased body mass index, female sex, COVID-19 hospitalization, non-white/multi-race were associated with higher disability burden. Dizziness and heavy limbs at infection were associated with disability regardless of hospitalization. Dyspnea and tremors were associated with disability in non-hospitalized individuals. Vaccination was protective against disability.

CONCLUSIONS: We observed a high burden of new disability associated with long COVID, which has serious implications for individual and societal health. Longitudinal evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.}, } @article {pmid37690286, year = {2023}, author = {Gupta, T and Najumuddin, and Rajendran, D and Gujral, A and Jangra, A}, title = {Metabolism configures immune response across multi-systems: Lessons from COVID-19.}, journal = {Advances in biological regulation}, volume = {90}, number = {}, pages = {100977}, doi = {10.1016/j.jbior.2023.100977}, pmid = {37690286}, issn = {2212-4934}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Heart Failure ; Inflammation ; Obesity ; Immunity ; *Diabetes Mellitus ; }, abstract = {Several studies over the last decade demonstrate the recruitment of immune cells, increased inflammatory cytokines, and chemokine in patients with metabolic diseases, including heart failure, parenchymal inflammation, obesity, tuberculosis, and diabetes mellitus. Metabolic rewiring of immune cells is associated with the severity and prevalence of these diseases. The risk of developing COVID-19/SARS-CoV-2 infection increases in patients with metabolic dysfunction (heart failure, diabetes mellitus, and obesity). Several etiologies, including fatigue, dyspnea, and dizziness, persist even months after COVID-19 infection, commonly known as Post-Acute Sequelae of CoV-2 (PASC) or long COVID. A chronic inflammatory state and metabolic dysfunction are the factors that contribute to long COVID. Here, this study explores the potential link between pathogenic metabolic and immune alterations across different organ systems that could underlie COVID-19 and PASC. These interactions could be utilized for targeted future therapeutic approaches.}, } @article {pmid37690207, year = {2023}, author = {Guillen-Burgos, HF and Galvez-Florez, JF and Moreno-Lopez, S and Gonzalez, I and Guillen, M and Anaya, JM}, title = {Factors associated with mental health outcomes after COVID-19: A 24-month follow-up longitudinal study.}, journal = {General hospital psychiatry}, volume = {84}, number = {}, pages = {241-249}, doi = {10.1016/j.genhosppsych.2023.08.009}, pmid = {37690207}, issn = {1873-7714}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; Prospective Studies ; Longitudinal Studies ; Follow-Up Studies ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Depression/diagnosis ; Anxiety/psychology ; *Stress Disorders, Post-Traumatic/psychology ; Outcome Assessment, Health Care ; }, abstract = {OBJECTIVE: Investigate the proportion of mental health outcomes (MHOs) and associated factors in COVID-19 survivors during a 24-month follow-up period.

METHOD: An observational, prospective study was performed in a teaching hospital in Barranquilla, Colombia, from April 1, 2020, to August 30, 2022. A cohort of 1565 COVID-19 survivors was recruited after discharge from the emergency room (ER), inpatient floor (IF), and intensive care unit (ICU) services and followed for 24 -months. The clinical assessment included screening scales for symptoms of anxiety, depressive, post-traumatic stress disorder (PTSD), and insomnia. Sociodemographic and clinical factors were also collected to identify possible associated factors. Descriptive, bivariate and mixed random-effect linear models were performed.

RESULTS: A total of 1565 patients were included, of whom 785 (50.35%) were men. A large proportion of patients with mental symptoms were identified. After 24-months, the proportions of anxiety, depression, PTSD, and insomnia symptoms remained high at 16.55%, 21.79%, 35.27%, and 23.86%, respectively. Social factors, location of hospital stays, physical comorbidities, and the severity of COVID-19 were significantly associated with anxiety, depression, PTSD, and insomnia symptoms.

CONCLUSIONS: COVID-19's 2-year deleterious impacts on mental health, as well as the variables influencing these findings, have been documented. These results should aid in the development of public health initiatives to reduce morbidity rates in post-COVID-19 patients.}, } @article {pmid37689093, year = {2023}, author = {Seibert, FS and Stervbo, U and Wiemers, L and Skrzypczyk, S and Hogeweg, M and Bertram, S and Kurek, J and Anft, M and Westhoff, TH and Babel, N}, title = {Severity of neurological Long-COVID symptoms correlates with increased level of autoantibodies targeting vasoregulatory and autonomic nervous system receptors.}, journal = {Autoimmunity reviews}, volume = {22}, number = {11}, pages = {103445}, doi = {10.1016/j.autrev.2023.103445}, pmid = {37689093}, issn = {1873-0183}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cross-Sectional Studies ; SARS-CoV-2 ; Autoantibodies ; Autonomic Nervous System ; Fatigue ; *Nervous System Diseases/diagnosis ; Receptor, Muscarinic M3 ; }, abstract = {BACKGROUND: The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting.

METHODS: This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires.

RESULTS: The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10[-9]) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087).

CONCLUSIONS: Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.}, } @article {pmid37688764, year = {2023}, author = {Fundora, MP and Kamidani, S and Oster, ME}, title = {COVID Vaccination as a Strategy for Cardiovascular Disease Prevention.}, journal = {Current cardiology reports}, volume = {25}, number = {10}, pages = {1327-1335}, pmid = {37688764}, issn = {1534-3170}, mesh = {Humans ; COVID-19 Vaccines ; *Cardiovascular Diseases/prevention & control ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; SARS-CoV-2 ; Vaccination ; }, abstract = {PURPOSE OF REVIEW: Cardiovascular (CV) disease is a known complication of SARS-CoV-2 infection. A clear benefit of COVID-19 vaccination is a reduction mortality; however, COVID-19 vaccination may also prevent cardiovascular disease (CVD). We aim to describe CV pathology associated with SARS-CoV-2 infection and describe how COVID-19 vaccination is a strategy for CVD prevention.

RECENT FINDINGS: The risks and benefits of COVID-19 vaccination have been widely studied. Analysis of individuals with and without pre-existing CVD has shown that COVID-19 vaccination can prevent morbidity associated with SARS-CoV-2 infection and reduce mortality. COVID-19 vaccination is effective in preventing myocardial infarction, cerebrovascular events, myopericarditis, and long COVID, all associated with CVD risk factors. Vaccination reduces mortality in patients with pre-existing CVD. Further study investigating ideal vaccination schedules for individuals with CVD should be undertaken to protect this vulnerable group and address new risks from variants of concern.}, } @article {pmid37686834, year = {2023}, author = {Chen, TB and Chang, CM and Yang, CC and Tsai, IJ and Wei, CY and Yang, HW and Yang, CP}, title = {Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686834}, issn = {2072-6643}, mesh = {Humans ; *Vitamin D ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Vitamins ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.}, } @article {pmid37686733, year = {2023}, author = {Pirro, M and Ferri, L and Piccioni, L and Bellucci, AM and Bartolucci, F and Russo, A and Piga, A and Ciaramaglia, PL and Lucangeli, M and Russo, AM and Cuzzocrea, S and Evangelista, M}, title = {What Is the Role of Palmitoylethanolamide Co-Ultramicronized with Luteolin on the Symptomatology Reported by Patients Suffering from Long COVID? A Retrospective Analysis Performed by a Group of General Practitioners in a Real-Life Setting.}, journal = {Nutrients}, volume = {15}, number = {17}, pages = {}, pmid = {37686733}, issn = {2072-6643}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Luteolin ; *COVID-19 ; *General Practitioners ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {Long COVID is a recognized post-viral syndrome characterized by neurological, somatic and neuropsychiatric symptoms that might last for long time after SARS-CoV-2 infection. An ever-growing number of patients come to the observation of General Practitioners complaining of mild or moderate symptoms after the resolution of the acute infection. Nine General Practitioners from the Rome area (Italy) performed a retrospective analysis in order to evaluate the role of the supplementation with Palmitoylethanolamide co-ultramicronized with Luteolin (PEALUT) on neurologic and clinical symptoms reported by their patients after COVID-19 resolution. Supplementation with PEALUT helped to improve all patient-reported symptoms, especially pain, anxiety and depression, fatigue, brain fog, anosmia and dysgeusia, leading to an overall improvement in patients' health status. To our knowledge these are the first data presented on Long COVID patients collected in a territorial setting. Despite their preliminary nature, these results highlight the pathogenetic role of "non-resolving" neuroinflammation in Long COVID development and consequently the importance of its control in the resolution of the pathology and put the focus on the General Practitioner as the primary figure for early detection and management of Long COVID syndrome in a real-life setting. Future randomized, controlled, perspective clinical trials are needed to confirm this preliminary observation.}, } @article {pmid37685544, year = {2023}, author = {Menichetti, F}, title = {The Potential Role of Hypothalamic Phospholipid Liposomes in the Supportive Therapy of Some Manifestations of Post-COVID-19 Condition: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Brain Fog.}, journal = {Journal of clinical medicine}, volume = {12}, number = {17}, pages = {}, pmid = {37685544}, issn = {2077-0383}, abstract = {Post-COVID-19 condition (commonly known as Long COVID) is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. Cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of the pathophysiology of Post-COVID-19 condition (PCC). Given the substantial lack of specific drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes, which have been on the market for several years as adjuvant therapy for cerebral metabolic alterations resulting from neuroendocrine disorders, might represent a potential option in an overall therapeutic strategy that aims to control PCC-associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their potential effectiveness in PCC. Our initial clinical experience seems to corroborate this rationale. Further controlled clinical research is warranted in order to verify this hypothesis.}, } @article {pmid37683768, year = {2023}, author = {Nazari, P and Pozzilli, P}, title = {Type 2 diabetes and Covid-19: Lessons learnt, unanswered questions and hints for the future.}, journal = {Diabetes research and clinical practice}, volume = {204}, number = {}, pages = {110896}, doi = {10.1016/j.diabres.2023.110896}, pmid = {37683768}, issn = {1872-8227}, mesh = {Humans ; *COVID-19/epidemiology ; *Diabetes Mellitus, Type 2/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Prediabetic State ; }, abstract = {Type 2 diabetes (T2DM) and COVID-19 represent a considerable burden of disease for patients and healthcare systems. New evidence is transpiring detailing the existence of a bidirectional relationship between T2DM and COVID-19. Alongside the acute influence of pre-existing T2DM on the course of COVID-19 and the exacerbation of dysglycemia following acute infection, long-term sequalae resulting from the synergistic interplay between the two is emerging, namely the development of COVID-induced diabetes and long-COVID in patients with pre-existing diabetes. This review presents our current understanding of the bidirectionality between these two conditions with a view to highlighting questions which remain unanswered and suggesting avenues for future research. In doing so, it emphasises critical gaps where concentrated research efforts are likely to yield the most beneficial improvements in understanding of the relationship between the two conditions, translating to tangible optimisations in care for the affected population.}, } @article {pmid37683237, year = {2023}, author = {La Sala, MS and Reinfeld, S and Constantino, E}, title = {Treatment of Long-COVID Neuropsychiatric Sequelae Using Tricyclic Antidepressants: A Case Series.}, journal = {Journal of clinical psychopharmacology}, volume = {43}, number = {5}, pages = {458-460}, doi = {10.1097/JCP.0000000000001725}, pmid = {37683237}, issn = {1533-712X}, mesh = {Humans ; *Antidepressive Agents, Tricyclic/adverse effects ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37682908, year = {2023}, author = {Meyerson, WU and Hoyle, RH}, title = {Pre-pandemic activity on a myalgic encephalomyelitis/chronic fatigue syndrome support forum is highly associated with later activity on a long COVID support forum for a variety of reasons: A mixed methods study.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0291173}, pmid = {37682908}, issn = {1932-6203}, mesh = {Humans ; *Fatigue Syndrome, Chronic/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/epidemiology ; SARS-CoV-2 ; }, abstract = {Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID share some clinical and social characteristics. We predicted that this would lead to an increased interaction between pre-pandemic members of an ME/CFS online support community and a long COVID community. We performed a mixed-methods retrospective observational study of the Reddit activity of 7,544 users active on Reddit's long COVID forum. From among 1600 forums, pre-pandemic activity specifically on a ME/CFS forum is the top predictor of later participation on the long COVID forum versus an acute COVID support forum. In the qualitative portion, motives for this co-participation included seeking mutual support and dual identification with both conditions. Some of this effect may be explained by pre-existing ME/CFS possibly being a risk factor for long COVID and/or SARS-CoV-2 infection being a cause of ME/CFS relapse. The high rate of ME/CFS patients seeking mutual support on a long COVID forum speaks to the long-suffering experience of these patients not feeling heard or respected, and the hope of some ME/CFS patients to gain legitimacy through the public's growing recognition of long COVID.}, } @article {pmid37682591, year = {2023}, author = {}, title = {Retraction.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {10}, pages = {575}, doi = {10.1111/pcn.13587}, pmid = {37682591}, issn = {1440-1819}, abstract = {Retraction: [Noda Y, Sato A, Fujii K, Nagano Y, Iwasa M, Hirahata K, Kitahata R, Osawa R, A pilot study of the effect of transcranial magnetic stimulation treatment on cognitive dysfunction associated with post COVID-19 condition, Psychiatry Clin. Neurosci. 2023; 77: 241-242 (https://onlinelibrary.wiley.com/doi/10.1111/pcn.13527)]. The above article from Psychiatry and Clinical Neurosciences, published online on 30 January 2023 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the authors, the Editors in Chief, Tadafumi Kato and Hidehiko Takahashi, and John Wiley & Sons Australia Ltd. The retraction has been issued because the content overlapped between this article and the following article published in Asian Journal of Psychiatry, "Real world research on transcranial magnetic stimulation treatment strategies for neuropsychiatric symptoms with long-COVID in Japan" by Yoshihiro Noda, Akiko Sato, Misaki Shichi, Ayano Sato, Kyoshiro Fujii, Mio Iwasa, Yasuhiro Nagano, Ryosuke Kitahata, Ryota Osawa. The authors declared that they would like to retract this article.}, } @article {pmid37681886, year = {2023}, author = {Vishwakarma, N and Goud, RB and Tirupattur, MP and Katwa, LC}, title = {The Eye of the Storm: Investigating the Long-Term Cardiovascular Effects of COVID-19 and Variants.}, journal = {Cells}, volume = {12}, number = {17}, pages = {}, pmid = {37681886}, issn = {2073-4409}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Heart ; *Cardiovascular System ; Disease Progression ; }, abstract = {COVID-19 had stormed through the world in early March of 2019, and on 5 May 2023, SARS-CoV-2 was officially declared to no longer be a global health emergency. The rise of new COVID-19 variants XBB.1.5 and XBB.1.16, a product of recombinant variants and sub-strains, has fueled a need for continued surveillance of the pandemic as they have been deemed increasingly infectious. Regardless of the severity of the variant, this has caused an increase in hospitalizations, a strain in resources, and a rise of concern for public health. In addition, there is a growing population of patients experiencing cardiovascular complications as a result of post-acute sequelae of COVID-19. This review aims to focus on what was known about SARS-CoV-2 and its past variants (Alpha, Delta, Omicron) and how the knowledge has grown today with new emerging variants, with an emphasis on cardiovascular complexities. We focus on the possible mechanisms that cause the observations of chronic cardiac conditions seen even after patients have recovered from the infection. Further understanding of these mechanisms will help to close the gap in knowledge on post-acute sequelae of COVID-19 and the differences between the effects of variants.}, } @article {pmid37681818, year = {2023}, author = {Khanafer, N and Henaff, L and Bennia, S and Termoz, A and Chapurlat, R and Escuret, V and Proriol, M and Duvert, F and Mena, C and Planckaert, C and Trehet-Mandez, N and Saadatian-Elahi, M and Vanhems, P}, title = {Factors Associated with Long COVID-19 in a French Multicentric Prospective Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {17}, pages = {}, pmid = {37681818}, issn = {1660-4601}, mesh = {Adult ; Humans ; Middle Aged ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/epidemiology ; Quality of Life ; *Ageusia ; }, abstract = {(1) Background: A substantial proportion of COVID-19 patients continue to experience long-lasting effects that hamper their quality of life. The objectives of this study were (1) to report the prevalence of persistent clinical symptoms 6-12 months after the onset of COVID-19 and (2) to identify potential factors at admission associated with the occurrence of long COVID. (2) Methods: A prospective study was conducted among COVID-19 adult patients, hospitalized in four French university hospitals. Patients were invited to two ambulatory follow-up medical visits, 6-8 months (visit #1) and one year (visit #2) after the onset of their COVID-19. A multivariate logistic regression was performed to assess factors associated with long COVID. (3) Results: In total, 189 patients participated in this study (mean age of 63.4 years). BMI > 30 kg/m[2] (aOR 3.52), AST levels between 31 and 42 U/L (aOR 8.68), and AST levels > 42 U/L (aOR 3.69) were associated with persistent clinical symptoms at visit #1. Anosmia (aOR 13.34), AST levels between 31 and 42 U/L (aOR 10.27), stay in ICU (aOR 5.43), pain (aOR 4.31), and longer time before hospitalization (aOR 1.14) were significantly associated with persistent clinical symptoms at visit #2. Patients with ageusia (aOR 0.17) had a lower risk of long COVID. (4) Conclusions: This study showed that some patients experienced persistent clinical symptoms one year after COVID-19 onset that were associated with some determinants at the acute phase/stage.}, } @article {pmid37681523, year = {2023}, author = {Kolson, DL}, title = {Can immunological imprinting drive neurological dysfunction in long COVID?.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {10}, pages = {3960-3962}, pmid = {37681523}, issn = {1460-2156}, support = {R01 NS122570/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {This scientific commentary refers to ‘Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses’ by Spatola et al. (https://doi.org/10.1093/brain/awad155).}, } @article {pmid37681420, year = {2024}, author = {Dodd, S and Mohebbi, M and O'Donohue, J and Matthews, G and Darley, DR and Berk, M}, title = {Psychiatric sequelae after SARS-Cov-2 infection: trajectory, predictors and associations in a longitudinal Australian cohort.}, journal = {Acta neuropsychiatrica}, volume = {36}, number = {4}, pages = {195-210}, doi = {10.1017/neu.2023.45}, pmid = {37681420}, issn = {1601-5215}, mesh = {Humans ; *COVID-19/psychology/complications/epidemiology ; Male ; Female ; Middle Aged ; Australia/epidemiology ; Longitudinal Studies ; Adult ; *SARS-CoV-2 ; *Quality of Life ; Depression/epidemiology/etiology/psychology ; Aged ; Mental Disorders/epidemiology/etiology/psychology ; Mental Health ; Severity of Illness Index ; Cohort Studies ; Biomarkers/blood ; Fatigue/psychology/etiology/epidemiology ; Surveys and Questionnaires ; }, abstract = {A relationship between SARS-CoV-2 infection and psychiatric symptoms has been identified but is still being fully investigated. Neuropsychiatric sequalae have been reported for several infectious agents and are not unexpected for SARS-CoV-2 infection. This study follows for 12 months a sample (N = 144) of people who have had a confirmed infection of SARS-CoV-2. Medical and neuropsychiatric data and biological specimens are collected at 6 study visits. The 34-item SPHERE questionnaire, the Depression in the Medically Ill instrument, the EQ-5D-5L quality of life instrument and the visual analogue scale of fatigue were administered at multiple timepoints and associations with measures of illness and inflammatory biomarkers were investigated using the generalised estimating equation. Associations between inflammatory biomarkers and mental health measures of various effect sizes were identified. A robust inverse association was found between mental health outcomes and long covid status, but not between mental health outcomes and covid illness severity. This study suggests that long covid may be the strongest predictor of neuropsychiatric symptoms amongst people who have been infected with SARS-CoV-2.}, } @article {pmid37680987, year = {2023}, author = {Chakraborty, C and Bhattacharya, M}, title = {The current landscape of long COVID clinical trials: NIH's RECOVER to Stanford Medicine's STOP-PASC initiative.}, journal = {Molecular therapy. Nucleic acids}, volume = {33}, number = {}, pages = {887-889}, pmid = {37680987}, issn = {2162-2531}, } @article {pmid37680625, year = {2023}, author = {An, AY and Baghela, A and Zhang, PGY and Blimkie, TM and Gauthier, J and Kaufmann, DE and Acton, E and Lee, AHY and Levesque, RC and Hancock, REW}, title = {Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1243689}, pmid = {37680625}, issn = {1664-3224}, support = {FDN-154287//CIHR/Canada ; }, mesh = {Adult ; Humans ; *Hemostatics ; *COVID-19 ; Blood Coagulation ; *Body Fluids ; Down-Regulation ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Persistent symptoms after COVID-19 infection ("long COVID") negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.

METHODS: RNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.

RESULTS: Compared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The "Resolved" endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of "Suppressive" and "Unresolved" endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.

DISCUSSION: This study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes ("Unresolved" and "Suppressive") were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment.}, } @article {pmid37678897, year = {2023}, author = {Dean, E}, title = {What happens inside a long covid clinic?.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1791}, doi = {10.1136/bmj.p1791}, pmid = {37678897}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid37678512, year = {2023}, author = {Løkke, FB and Hansen, KS and Dalgaard, LS and Öbrink-Hansen, K and Schiøttz-Christensen, B and Leth, S}, title = {Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV - Lessons to learn in long COVID?.}, journal = {Infectious diseases now}, volume = {53}, number = {8}, pages = {104779}, doi = {10.1016/j.idnow.2023.104779}, pmid = {37678512}, issn = {2666-9919}, mesh = {Humans ; *Severe acute respiratory syndrome-related coronavirus ; *COVID-19/complications ; *Middle East Respiratory Syndrome Coronavirus ; Post-Acute COVID-19 Syndrome ; *Influenza, Human/complications/epidemiology ; SARS-CoV-2 ; Pandemics ; Quality of Life ; }, abstract = {The COVID-19 pandemic has affected millions of people worldwide, and while the mortality rate remains the primary concern, it is becoming increasingly apparent that many COVID-19 survivors experience long-term sequelae, representing a major concern for both themselves and healthcare providers. Comparing long-term sequelae following COVID-19 to those of other respiratory viruses such as influenza, MERS-CoV, and SARS-CoV-1 is an essential step toward understanding the extent and impact of these sequelae. A literature search was carried out using the PubMed. database. Search-terms included "persistent", "long-term", "chronic", and MeSH-terms for SARS-CoV-1, MERS-CoV and Influenza. Only English-language articles were selected. Articles were screened by title/abstract and full-text readings. Key points for comparison were persistent symptoms > 4 weeks, virus type, study design, population size, admission status, methods, and findings. Thirty-one articles were included: 19 on SARS-CoV-1, 10 on influenza, and 2 on MERS-CoV-survivors. Damage to the respiratory system was the main long-term manifestation after the acute phase of infection. Quality of life-related and psychological sequelae were the second and third most widely reported symptoms, respectively. Consistent with long-term sequelae from COVID-19, persisting cardiovascular, neurological, musculoskeletal, gastrointestinal impairments were also reported. In summary, the long-term sequelae following COVID-19 are a significant concern, and while long-term sequelae following influenza, MERS-CoV, and SARS-CoV-1 have also been reported, their prevalence and severity are less clear. It is essential to continue to study and monitor the long-term effects of all respiratory viruses so as to improve our understanding and develop strategies for prevention and treatment.}, } @article {pmid37675987, year = {2023}, author = {Marcilla-Toribio, I and Martinez-Andres, M and Moratalla-Cebrian, ML and Jandhyala, R and Femi-Ajao, O and Galan-Moya, EM}, title = {Adaptation and validation of the PAC-19QoL-specific quality of life questionnaire for the Spanish population with long COVID.}, journal = {Current medical research and opinion}, volume = {39}, number = {12}, pages = {1685-1693}, doi = {10.1080/03007995.2023.2256222}, pmid = {37675987}, issn = {1473-4877}, mesh = {Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Reproducibility of Results ; Cross-Sectional Studies ; *COVID-19 ; Surveys and Questionnaires ; Psychometrics ; }, abstract = {INTRODUCTION: The post-acute (long) COVID-19 Quality of Life instrument is the only specific instrument designed to assess the quality of life in long COVID patients. The present study aims to make a transcultural adaptation and validation into Spanish of the disease-specific (long COVID) quality of life instrument, post-acute (long) COVID-19 Quality of Life, to have a tool for objective measurement of quality of life in this population.

METHODS: A descriptive cross-sectional study was divided into two phases. In phase one, the translation and cultural adaptation of the questionnaire was performed, while in phase two, the questionnaire was validated. The Spanish version of the questionnaire was used with a sample of 206 people, 40 males (19.4%) and 166 females (80.6%), with an age range between 21 and 70 years old. Participants completed the questionnaire through an online platform. Internal consistency, construct validity, convergent validity, test-retest reliability, and ceiling and floor effects of the Spanish version were analyzed.

RESULTS: The Spanish version of the post-acute (long) COVID-19 Quality of Life instrument showed high internal consistency, with Cronbach's alpha= 0.922 and an intraclass correlation coefficient of 0.936. Mean scores obtained in the PAC-19QoL and SF-12 questionnaires showed that those who had a worse quality of life in the SF-12 tool also a had worse quality of life in the PAC-19QoL tool.

CONCLUSIONS: This study shows that the Spanish version of the post-acute (long) COVID-19 Quality of Life instrument is an appropriate and valid tool for assessing the quality of life of long COVID patients.}, } @article {pmid37675960, year = {2024}, author = {Hilas, O and Caliendo, T}, title = {Intranasal Theophylline: Potential Treatment for Long COVID Olfactory Dysfunction?.}, journal = {The Annals of pharmacotherapy}, volume = {58}, number = {6}, pages = {661-662}, doi = {10.1177/10600280231194960}, pmid = {37675960}, issn = {1542-6270}, mesh = {Humans ; *Theophylline/administration & dosage/therapeutic use ; *Administration, Intranasal ; *COVID-19/complications ; *Olfaction Disorders/drug therapy ; *COVID-19 Drug Treatment ; SARS-CoV-2 ; }, } @article {pmid37675861, year = {2023}, author = {Das, S and Kumar, S}, title = {Exploring the mechanisms of long COVID: Insights from computational analysis of SARS-CoV-2 gene expression and symptom associations.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29077}, doi = {10.1002/jmv.29077}, pmid = {37675861}, issn = {1096-9071}, mesh = {*Post-Acute COVID-19 Syndrome/drug therapy/genetics/pathology ; Humans ; *Gene Expression Profiling ; Female ; Child ; Precision Medicine ; Receptors, G-Protein-Coupled ; Biomarkers/analysis ; Male ; }, abstract = {Long coronavirus disease (COVID) has emerged as a global health issue, affecting a substantial number of people worldwide. However, the underlying mechanisms that contribute to the persistence of symptoms in long COVID remain obscure, impeding the development of effective diagnostic and therapeutic interventions. In this study, we utilized computational methods to examine the gene expression profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their associations with the wide range of symptoms observed in long COVID patients. Using a comprehensive data set comprising over 255 symptoms affecting multiple organ systems, we identified differentially expressed genes and investigated their functional similarity, leading to the identification of key genes with the potential to serve as biomarkers for long COVID. We identified the participation of hub genes associated with G-protein-coupled receptors (GPCRs), which are essential regulators of T-cell immunity and viral infection responses. Among the identified common genes were CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1, which play a crucial role in modulating T-cell immunity via GPCR and contribute to a variety of symptoms, including autoimmunity, cardiovascular disorders, dermatological manifestations, gastrointestinal complications, pulmonary impairments, reproductive and genitourinary dysfunctions, and endocrine abnormalities. GPCRs and associated genes are pivotal in immune regulation and cellular functions, and their dysregulation may contribute to the persistent immune responses, chronic inflammation, and tissue abnormalities observed in long COVID. Targeting GPCRs and their associated pathways could offer promising therapeutic strategies to manage symptoms and improve outcomes for those experiencing long COVID. However, the complex mechanisms underlying the condition require continued study to develop effective treatments. Our study has significant implications for understanding the molecular mechanisms underlying long COVID and for identifying potential therapeutic targets. In addition, we have developed a comprehensive website (https://longcovid.omicstutorials.com/) that provides a curated list of biomarker-identified genes and treatment recommendations for each specific disease, thereby facilitating informed clinical decision-making and improved patient management. Our study contributes to the understanding of this debilitating disease, paving the way for improved diagnostic precision, and individualized therapeutic interventions.}, } @article {pmid37675472, year = {2023}, author = {Colosio, M and Brocca, L and Gatti, MF and Neri, M and Crea, E and Cadile, F and Canepari, M and Pellegrino, MA and Polla, B and Porcelli, S and Bottinelli, R}, title = {Structural and functional impairments of skeletal muscle in patients with postacute sequelae of SARS-CoV-2 infection.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {135}, number = {4}, pages = {902-917}, doi = {10.1152/japplphysiol.00158.2023}, pmid = {37675472}, issn = {1522-1601}, mesh = {Humans ; Adult ; Middle Aged ; Aged ; *Quality of Life ; *COVID-19/pathology ; SARS-CoV-2 ; Muscle, Skeletal/physiology ; Muscle Weakness/etiology ; }, abstract = {Following acute coronavirus disease 2019 (COVID-19), a substantial proportion of patients showed symptoms and sequelae for several months, namely the postacute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness, and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle. At least 3 mo after infection, nonhospitalized patients with PASC (n = 11, age: 54 ± 11 yr; PASC) and patients without long-term symptoms (n = 12, age: 49 ± 9 yr; CTRL) visited the laboratory on four nonconsecutive days. Spirometry, lung diffusion capacity, and quality of life were assessed at rest. A cardiopulmonary incremental exercise test was performed. Oxygen consumption (V̇o2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies. Pulmonary and cardiac functions were within normal range in all patients. V̇o2peak was lower in PASC than CTRL (24.7 ± 5.0 vs. 32.9 ± 7.4 mL·min[-1]·kg[-1], respectively, P < 0.05). V̇o2 kinetics was slower in PASC than CTRL (41 ± 12 vs. 30 ± 9 s[-1], P < 0.05). k was lower in PASC than CTRL (1.54 ± 0.49 vs. 2.07 ± 0.51 min[-1], P < 0.05). Citrate synthase, peroxisome proliferator-activated receptor-γ coactivator (PGC)1α, and JO2 for mitochondrial complex II were significantly lower in PASC vs. CTRL (all P values <0.05). In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to "peripheral" determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome, therefore, appears to negatively impact skeletal muscle function, although the disease is a heterogeneous condition.NEW & NOTEWORTHY Several months after mild acute SARS-CoV-2 infection, a substantial proportion of patients present persisting, and often debilitating, symptoms and sequelae. These patients show reduced quality of life due to exercise intolerance, muscle weakness, and fatigue. The present study supports the hypothesis that "peripheral" impairments at skeletal muscle level, namely, reduced mitochondrial function and markers of mitochondrial biogenesis, are major determinants of exercise intolerance and fatigue, "central" phenomena at respiratory, and cardiac level being less relevant.}, } @article {pmid37674565, year = {2023}, author = {Nyasulu, PS and Tamuzi, JL and Erasmus, RT}, title = {Burden, causation, and particularities of Long COVID in African populations: A rapid systematic review.}, journal = {IJID regions}, volume = {8}, number = {}, pages = {137-144}, pmid = {37674565}, issn = {2772-7076}, abstract = {OBJECTIVES: To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations.

METHODS: A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). A narrative synthesis was also performed.

RESULTS: We included 14 studies from seven African countries, totaling 6030 previously SARS-CoV-2 infected participants and 2954 long COVID patients. Long COVID had a pooled prevalence of 41% (26-56%). Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% (26-56%), 25% (12-38%), and 40% (12-68%), respectively. Long COVID was mainly associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, COVID-19 severity, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness (P ≤0.05). High microclot and platelet-poor plasma viscosity explained the pathophysiology of long COVID.

CONCLUSION: Long COVID prevalence in Africa was comparable to the global prevalence. The most common symptoms were higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.Systematic review registration: PROSPERO CRD42023430024.}, } @article {pmid37672869, year = {2023}, author = {Antony, B and Blau, H and Casiraghi, E and Loomba, JJ and Callahan, TJ and Laraway, BJ and Wilkins, KJ and Antonescu, CC and Valentini, G and Williams, AE and Robinson, PN and Reese, JT and Murali, TM and , }, title = {Predictive models of long COVID.}, journal = {EBioMedicine}, volume = {96}, number = {}, pages = {104777}, pmid = {37672869}, issn = {2352-3964}, support = {UM1 TR004404/TR/NCATS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UM1 TR004556/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Drug Treatment ; Machine Learning ; Obesity ; }, abstract = {BACKGROUND: The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future.

METHODS: We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models - logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the 'long COVID' label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n = 2,190,579; diagnosed with long COVID = 17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741).

FINDINGS: LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75.

INTERPRETATION: ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology.

FUNDING: NCATS U24 TR002306, NCATS UL1 TR003015, Axle Informatics Subcontract: NCATS-P00438-B, NIH/NIDDK/OD, PSR2015-1720GVALE_01, G43C22001320007, and Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231.}, } @article {pmid37672832, year = {2023}, author = {Walkowiak, MP and Domaradzki, J and Walkowiak, D}, title = {Unmasking the COVID-19 pandemic prevention gains: excess mortality reversal in 2022.}, journal = {Public health}, volume = {223}, number = {}, pages = {193-201}, doi = {10.1016/j.puhe.2023.08.004}, pmid = {37672832}, issn = {1476-5616}, mesh = {Humans ; *COVID-19/prevention & control ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Cost-Benefit Analysis ; Government ; }, abstract = {OBJECTIVES: The purpose of this study was to assess the long-term effectiveness of COVID-19 pandemic prevention measures in saving lives after European governments began to lift restrictions.

STUDY DESIGN: Excess mortality interrupted time series.

METHODS: Country-level weekly data on deaths were fitted to the Poisson mixed linear model to estimate excess deaths. Based on this estimate, the percentage of excess deaths above the baseline during the pandemic (week 11 in 2020 to week 15 in 2022) (when public health interventions were in place) and during the post-pandemic period (week 16 in 2022 to week 52 in 2022) were calculated. These results were fitted to the linear regression model to determine any potential relationship between mortality during these two periods.

RESULTS: The model used in this study had high predictive value (adjusted R[2] = 59.4%). Mortality during the endemic (post-pandemic) period alone increased by 7.2% (95% confidence interval [CI]: 5.7, 8.6) above baseline, while each percentage increase in mortality during the pandemic corresponded to a 0.357% reduction (95% CI: 0.243, 0.471) in mortality during the post-pandemic period.

CONCLUSIONS: The most successful countries in terms of protective measures also experienced the highest mortality rates after restrictions were lifted. The model used in this study clearly shows a measure of bidirectional mortality displacement that is sufficiently clear to mask any impact of long COVID on overall mortality. Results from this study also seriously impact previous cost-benefit analyses of pandemic prevention measures, since, according to the current model, 12.2% (95% CI: 8.3, 16.1) of the gains achieved in pandemic containment were lost after restrictions were lifted.}, } @article {pmid37672298, year = {2023}, author = {Harris, E}, title = {Some People Still Have Long COVID Symptoms After 2 Years.}, journal = {JAMA}, volume = {330}, number = {12}, pages = {1127}, doi = {10.1001/jama.2023.16677}, pmid = {37672298}, issn = {1538-3598}, mesh = {Humans ; COVID-19 ; *Post-Acute COVID-19 Syndrome/diagnosis ; Time Factors ; }, } @article {pmid37671223, year = {2023}, author = {Avula, VCR and Amalakanti, S and M, S and Fasiha, A}, title = {Anxiety and Depression in COVID Survivors - A Cross-Sectional Study Six Months Past the Acute Illness.}, journal = {Cureus}, volume = {15}, number = {8}, pages = {e42971}, pmid = {37671223}, issn = {2168-8184}, abstract = {Background Studies exploring the long-term psychiatric sequelae of COVID-19 are sparse. We aimed to assess depression and anxiety six months after recovery and the association between disease severity and psychiatric sequelae. Material and methods Our study was a comparative study conducted on COVID-19 disease survivors at a tertiary hospital. We compared Hamilton Depression Rating Scale (HDRS) scores and Hamilton Anxiety Rating Scale (HAM-A) scores between mild (n=50), moderate (n=50), severe cases (n=50), and controls (n=50). We assessed the severity of depression and anxiety using the HDRS and the HAM-A. Cases: First-time COVID-19 survivors six months post-recovery. Cases were healthy pre-COVID. To the study date, controls were negative for COVID-19 reverse transcription polymerase chain reaction (RT-PCR). Results Our study of 200 subjects indicated that mean (mean, SD) HAM-A scores in cases (14.7, 5.6) were higher than controls (7.9, 1.7), and HDRS scores in cases (17.3, 6.3) were higher than controls (7.5, 1.9). HAM-A scores in severe cases (19.5, 4.8) were higher than in moderate cases (17.0, 3.9), and scores in moderate cases were higher than in mild cases (10.6, 2.4). HDRS scores in severe cases (22.5, 5.9) were higher than in moderate cases (16.4, 3.2), and scores in moderate cases were higher than in mild cases (14.4, 2.5). Among the cases, there was a positive correlation between the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HDRS) scores and the duration of hospital stay, ICU stay, and use of invasive oxygen. These parameters were not applicable to the controls; hence, they were not included in the comparative analysis. Conclusions Patients, even after six months of recovery from COVID-19, had symptoms of anxiety and depression. The severity of anxiety and depression in survivors correlates with the severity of the COVID-19 disease.}, } @article {pmid37670400, year = {2023}, author = {Rigo, S and Urechie, V and Diedrich, A and Okamoto, LE and Biaggioni, I and Shibao, CA}, title = {Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome - a case-control study.}, journal = {Bioelectronic medicine}, volume = {9}, number = {1}, pages = {19}, pmid = {37670400}, issn = {2332-8886}, support = {R01 HL142583/HL/NHLBI NIH HHS/United States ; R01 HL157584/HL/NHLBI NIH HHS/United States ; }, abstract = {PURPOSE: Eighty percent of patients infected by SARS-CoV-2 report persistence of one symptom beyond the 4-week convalescent period. Those with orthostatic tachycardia and orthostatic symptoms mimicking postural tachycardia syndrome, they are defined as Long-COVID POTS [LCP]. This case-control study investigated potential differences in autonomic cardiovascular regulation between LCP patients and healthy controls.

METHODS: Thirteen LCP and 16 healthy controls, all female subjects, were studied without medications. Continuous blood pressure and ECG were recorded during orthostatic stress test, respiratory sinus arrhythmia, and Valsalva maneuver. Time domain and power spectral analysis of heart rate [HR] and systolic blood pressure [SBP] variability were computed characterizing cardiac autonomic control and sympathetic peripheral vasoconstriction.

RESULTS: LCP had higher deltaHR (+ 40 ± 6 vs. + 21 ± 3 bpm, p = 0.004) and deltaSBP (+ 8 ± 4 vs. -1 ± 2 mmHg, p = 0.04) upon standing; 47% had impaired Valsalva maneuver ratio compared with 6.2% in controls (p = 0.01). Spectral analysis revealed that LCP had lower RMSSD (32.1 ± 4.6 vs. 48.9 ± 6.8 ms, p = 0.04) and HFRRI, both in absolute (349 ± 105 vs. 851 ± 253ms[2], p = 0.03) and normalized units (32 ± 4 vs. 46 ± 4 n.u., p = 0.02). LFSBP was similar between groups.

CONCLUSIONS: LCP have reduced cardiovagal modulation, but normal sympathetic cardiac and vasoconstrictive functions. Impaired parasympathetic function may contribute to the pathogenesis of Long-COVID POTS syndrome.}, } @article {pmid37670171, year = {2023}, author = {Rass, V and Tymoszuk, P and Sahanic, S and Heim, B and Ausserhofer, D and Lindner, A and Kofler, M and Mahlknecht, P and Boehm, A and Hüfner, K and Pizzini, A and Sonnweber, T and Kurz, K and Pfeifer, B and Kiechl, S and Peball, M and Kindl, P and Putnina, L and Fava, E and Djamshidian, A and Huber, A and Wiedermann, CJ and Sperner-Unterweger, B and Wöll, E and Beer, R and Schiefecker, AJ and Bellmann-Weiler, R and Bachler, H and Tancevski, I and Pfausler, B and Piccoliori, G and Seppi, K and Weiss, G and Löffler-Ragg, J and Helbok, R}, title = {Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {280}, number = {11}, pages = {5115-5128}, pmid = {37670171}, issn = {1434-4726}, support = {GZ 71934//Land Tirol/ ; IIS 1199-0424//Boehringer Ingelheim/ ; }, mesh = {Female ; Humans ; *COVID-19/complications/epidemiology ; *Olfaction Disorders/epidemiology/etiology/diagnosis ; Quality of Life ; SARS-CoV-2 ; Smell ; Taste ; Taste Disorders/epidemiology/etiology ; }, abstract = {PURPOSE: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health.

METHODS: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering.

RESULTS: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints.

CONCLUSION: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health.

STUDY REGISTRATION: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).}, } @article {pmid37669692, year = {2023}, author = {Clark, AD and Cumpstey, AF and Santolini, J and Jackson, AA and Feelisch, M}, title = {Uncoupled redox stress: how a temporal misalignment of redox-regulated processes and circadian rhythmicity exacerbates the stressed state.}, journal = {Open biology}, volume = {13}, number = {9}, pages = {230151}, pmid = {37669692}, issn = {2046-2441}, mesh = {Animals ; Humans ; *Ecosystem ; Health Promotion ; *COVID-19 ; SARS-CoV-2 ; Circadian Rhythm ; Oxidation-Reduction ; }, abstract = {Diurnal and seasonal rhythmicity, entrained by environmental and nutritional cues, is a vital part of all life on Earth operating at every level of organization; from individual cells, to multicellular organisms, whole ecosystems and societies. Redox processes are intrinsic to physiological function and circadian regulation, but how they are integrated with other regulatory processes at the whole-body level is poorly understood. Circadian misalignment triggered by a major stressor (e.g. viral infection with SARS-CoV-2) or recurring stressors of lesser magnitude such as shift work elicit a complex stress response that leads to desynchronization of metabolic processes. This in turn challenges the system's ability to achieve redox balance due to alterations in metabolic fluxes (redox rewiring). We infer that the emerging 'alternative redox states' do not always revert readily to their evolved natural states; 'Long COVID' and other complex disorders of unknown aetiology are the clinical manifestations of such rearrangements. To better support and successfully manage bodily resilience to major stress and other redox challenges needs a clear perspective on the pattern of the hysteretic response for the interaction between the redox system and the circadian clock. Characterization of this system requires repeated (ideally continuous) recording of relevant clinical measures of the stress responses and whole-body redox state (temporal redox phenotyping). The human/animal body is a complex 'system of systems' with multi-level buffering capabilities, and it requires consideration of the wider dynamic context to identify a limited number of stress-markers suitable for routine clinical decision making. Systematically mapping the patterns and dynamics of redox biomarkers along the stressor/disease trajectory will provide an operational model of whole-body redox regulation/balance that can serve as basis for the identification of effective interventions which promote health by enhancing resilience.}, } @article {pmid37669253, year = {2023}, author = {Silwal, S and Parajuli, K and Acharya, A and Ghimire, A and Pandey, S and Pandey, A and Poudyal, A and Bista, B and Gyanwali, P and Dhimal, M}, title = {Physical, mental and social status after COVID-19 recovery in Nepal: A mixed method study.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0290693}, pmid = {37669253}, issn = {1932-6203}, mesh = {Humans ; *Social Status ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Nepal ; *COVID-19 ; }, abstract = {BACKGROUND: Nepal has been devastated by an unprecedented COVID-19 outbreak, affecting people emotionally, physically, and socially, resulting in significant morbidity and mortality. Approximately 10% of COVID-19 affected people have symptoms that last more than 3-4 weeks and experience numerous symptoms causing an impact on everyday functioning, social, and cognitive function. Thus, it is vital to know about the recovered patient's health status and undertake rigorous examinations to detect and treat infections. Hence, this study aims to assess the health status of COVID-19 post-recovery patients in Nepal.

METHOD: A descriptive cross-sectional mixed-method study was conducted in all seven provinces of Nepal. A total of 552 interviews were conducted for the quantitative study, and 25 in-depth interviews were conducted for the qualitative study among above 18 years COVID-19-recovered patients. The data was gathered over the phone through the purposive sampling method The results of a descriptive and thematic analysis were interpreted.

FINDING: The majority (more than 80%) of the recovered patients could routinely perform household duties, activities outside the home, and financial job accounting. However, a few of them required assistance in carrying out all of those tasks. Prior and then after COVID-19 infection, smoking habits reduced by about one-tenth and alcohol intake decreased by a twelve percent. A qualitative finding revealed that the majority of COVID-19 symptomatic patients experienced a variety of physical symptoms such as fever, headache, body pain, fatigue, tiredness, sore throat, cough, loss of taste, loss of smell, sneezing, loss of appetite, and difficulty breathing, while others felt completely fine after being recovered. Furthermore, there was no variation in the daily functional activities of the majority of the recovered patients, while a few were found conducting fewer activities than usual because they were concerned about their health. For social health, quantitative data indicated that more than half of the participants' social health was severely impacted. According to the IDI, the majority of the interviewees perceived society's ignorance and misbehavior. Family members were the most often solicited sources of support. Some participants got care and assistance, but the majority did not get affection or love from their relatives. Moreover, regarding mental health, 15 percent of participants had repeated disturbing and unwanted thoughts about COVID-19 after being recovered, 16 percent tried to avoid information on COVID-19 and 7 .7 percent of people had unfavorable ideas or sentiments about themselves. More than 16 percent of participants reported feeling some level of stress related to the workplace and home. While in-depth interviews participants revealed that COVID-infected patients who were asymptomatic didn't experience any emotional change in them but recovered patients who are symptomatic symptoms had anxiety and still being conscious of COVID-19 in fear of getting infected again Additionally, it was discovered that participants' mental health is influenced by ignorance of society, as well as by fake news posted to social media.

CONCLUSION: COVID-19 infection has had an impact on physical, mental, and social well-being. Hence, to aid in the early recovery of COVID-19 patients, provision of evaluating and reporting the clinical features, early detection and management of long COVID case is needed from the local and provincial and central government of Nepal.}, } @article {pmid37667865, year = {2023}, author = {Coscia, F and Di Filippo, ES and Gigliotti, PV and Fano Illic, G}, title = {Effect of physical activity on long COVID fatigue: an unsolved enigma.}, journal = {European journal of translational myology}, volume = {33}, number = {3}, pages = {}, pmid = {37667865}, issn = {2037-7452}, abstract = {Covid-19 disease is well documented and often the most common symptoms include myalgia and muscle fatigue. Approximately 10% of those infected complain of persistent fatigue even many months after the end of the acute phase of the disease. This gives rise to a condition different from the previous one and commonly known as 'post-acute COVID-19 syndrome' or simply Long-COVID. Although the origin of muscle fatigue is multifactorial, the state of prolonged fatigue observed in the Long-COVID syndrome suggests the existence of a possible state of atrophy or rather acute sarcopenia. Under these conditions, the use of physical activity programs can effectively counteract the state of atrophy underlying the fatigue phenomena observed. If this is also the situation during the Long-COVID, the muscular symptom should be positively influenced by the administration of programmed physical activity cycles. In fact, in patients with Long-COVID, the few published papers seem to indicate that patients who are physically active and who make an effort to engage in physical activity even during the illness have decreased duration and intensity of the illness. However, analysis of the studies in the literature also suggests that a small percentage of people with Long-COVID do not appear to benefit from the application of physical activity programs, so further studies on homogeneous samples are needed to provide a firm answer to the question: can planned physical activity help patients during the pathological course of Long-COVID?}, } @article {pmid37667487, year = {2024}, author = {Luedke, JC and Vargas, G and Jashar, DT and Morrow, A and Malone, LA and Ng, R}, title = {[Formula: see text] Cognitive disengagement syndrome in pediatric patients with long COVID: associations with mood, anxiety, and functional impairment.}, journal = {Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence}, volume = {30}, number = {4}, pages = {652-672}, doi = {10.1080/09297049.2023.2252967}, pmid = {37667487}, issn = {1744-4136}, mesh = {Humans ; Female ; Male ; Child ; Adolescent ; *COVID-19/psychology/complications ; *Anxiety/psychology ; Retrospective Studies ; Cognitive Dysfunction/psychology/etiology ; Post-Acute COVID-19 Syndrome ; Affect ; }, abstract = {Children with long COVID often report symptoms that overlap with cognitive disengagement syndrome (CDS, previously sluggish cognitive tempo (SCT)), a set of behaviors distinct from attention-deficit/hyperactivity disorder (ADHD) including excessive daydreaming, mental fogginess, and slowed behavior and thinking. Those with long COVID also frequently report low mood and anxiety, which are linked to CDS. The relationships between cognitive difficulties, mood, and functional impairment have yet to be explored in pediatric long COVID. Specifically, it is unclear how much cognitive difficulties (CDS, inattention) contribute to functional impairment, when accounting for mood/anxiety symptoms in this population. Retrospective parent-reported data was collected from 34 patients with long COVID (22 females, Mage = 14.06 years, SD = 2.85, range 7-19) referred for neuropsychological consultation through a multidisciplinary Post-COVID-19 clinic. Compared to community and clinically referred samples, on average, long COVID patients showed elevated CDS symptoms, including Sluggish/sleepy (e.g., fatigue) and Low Initiation subscales (e.g., difficulty performing goal directed behaviors). Low Initiation, mood, anxiety, and inattention were associated with functional impairment. In multiple hierarchical regression models, after controlling for mood and anxiety, Low Initiation and inattention were no longer predictive of functional impairment. Instead, anxiety remained the sole predictor of functional impairment. Our results demonstrate that children with long COVID have high levels of CDS symptoms. The association between cognitive difficulties and functional impairment dissipated with the inclusion of mood and anxiety, suggesting behavioral health interventions targeting anxiety may help improve daily functioning and quality of life in pediatric long COVID patients.}, } @article {pmid37667413, year = {2023}, author = {Johansson, MW and Balnis, J and Muehlbauer, LK and Bukhman, YV and Stefely, MS and Overmyer, KA and Vancavage, R and Tiwari, A and Adhikari, AR and Feustel, PJ and Schwartz, BS and Coon, JJ and Stewart, R and Jaitovich, A and Mosher, DF}, title = {Decreased plasma cartilage acidic protein 1 in COVID-19.}, journal = {Physiological reports}, volume = {11}, number = {17}, pages = {e15814}, pmid = {37667413}, issn = {2051-817X}, support = {R01 HL160661/HL/NHLBI NIH HHS/United States ; R01 AG066179/AG/NIA NIH HHS/United States ; R01 AI173035/AI/NIAID NIH HHS/United States ; P41 GM108538/GM/NIGMS NIH HHS/United States ; K01 HL130704/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Calcium-Binding Proteins/blood ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Proteomics ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {Cartilage acidic protein-1 (CRTAC1) is produced by several cell types, including Type 2 alveolar epithelial (T2AE) cells that are targeted by SARS-CoV2. Plasma CRTAC1 is known based on proteomic surveys to be low in patients with severe COVID-19. Using an ELISA, we found that patients treated for COVID-19 in an ICU almost uniformly had plasma concentrations of CRTAC1 below those of healthy controls. Magnitude of decrease in CRTAC1 distinguished COVID-19 from other causes of acute respiratory decompensation and correlated with established metrics of COVID-19 severity. CRTAC1 concentrations below those of controls were found in some patients a year after hospitalization with COVID-19, long COVID after less severe COVID-19, or chronic obstructive pulmonary disease. Decreases in CRTAC1 in severe COVID-19 correlated (r = 0.37, p = 0.0001) with decreases in CFP (properdin), which interacts with CRTAC1. Thus, decreases of CRTAC1 associated with severe COVID-19 may result from loss of production by T2AE cells or co-depletion with CFP. Determination of significance of and reasons behind decreased CRTAC1 concentration in a subset of patients with long COVID will require analysis of roles of preexisting lung disease, impact of prior acute COVID-19, age, and other confounding variables in a larger number of patients.}, } @article {pmid37667052, year = {2023}, author = {Proal, AD and VanElzakker, MB and Aleman, S and Bach, K and Boribong, BP and Buggert, M and Cherry, S and Chertow, DS and Davies, HE and Dupont, CL and Deeks, SG and Eimer, W and Ely, EW and Fasano, A and Freire, M and Geng, LN and Griffin, DE and Henrich, TJ and Iwasaki, A and Izquierdo-Garcia, D and Locci, M and Mehandru, S and Painter, MM and Peluso, MJ and Pretorius, E and Price, DA and Putrino, D and Scheuermann, RH and Tan, GS and Tanzi, RE and VanBrocklin, HF and Yonker, LM and Wherry, EJ}, title = {SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).}, journal = {Nature immunology}, volume = {24}, number = {10}, pages = {1616-1627}, pmid = {37667052}, issn = {1529-2916}, support = {K08 HL143183/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; RNA, Viral/genetics ; SARS-CoV-2 ; Antiviral Agents ; Disease Progression ; }, abstract = {Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a 'reservoir'. This reservoir could modulate host immune responses or release viral proteins into the circulation. Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.}, } @article {pmid37665981, year = {2024}, author = {Hedberg, P and Nauclér, P}, title = {Post-COVID-19 Condition After SARS-CoV-2 Infections During the Omicron Surge vs the Delta, Alpha, and Wild Type Periods in Stockholm, Sweden.}, journal = {The Journal of infectious diseases}, volume = {229}, number = {1}, pages = {133-136}, pmid = {37665981}, issn = {1537-6613}, support = {2021-04809//Swedish Research Council/ ; 101046016//European Union's Horizon Europe Research and Innovation Programme/ ; }, mesh = {Humans ; *COVID-19 ; Sweden/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Chronic Disease ; }, abstract = {Little is known about the post-COVID-19 condition (PCC) after infections with different SARS-CoV-2 variants. We investigated the risk of PCC diagnosis after primary omicron infections as compared with preceding variants in population-based cohorts in Stockholm, Sweden. When compared with omicron (n = 215 279, 0.2% receiving a PCC diagnosis), the adjusted hazard ratio (95% CI) was 3.26 (2.80-3.80) for delta (n = 52 182, 0.5% PCC diagnosis), 5.33 (4.73-5.99) for alpha (n = 97 978, 1.0% PCC diagnosis), and 6.31 (5.64-7.06) for the wild type (n = 107 920, 1.3% PCC diagnosis). These findings were consistent across all subgroup analyses except among those treated in the intensive care unit.}, } @article {pmid37665556, year = {2023}, author = {Tosato, M and Calvani, R and Ciciarello, F and Galluzzo, V and Martone, AM and Zazzara, MB and Pais, C and Savera, G and Robles, MC and Ramirez, M and Landi, F and , }, title = {Malnutrition in COVID-19 survivors: prevalence and risk factors.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {10}, pages = {2257-2265}, pmid = {37665556}, issn = {1720-8319}, mesh = {Humans ; Male ; Aged ; Prevalence ; *COVID-19/epidemiology ; *Malnutrition/epidemiology ; Nutritional Status ; Risk Factors ; Nutrition Assessment ; Survivors ; }, abstract = {BACKGROUND: Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients.

AIM: To assess the prevalence of malnutrition and identify its associated factors in COVID-19 survivors.

METHODS: Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria.

RESULTS: Prevalence of malnutrition was 22% at 4-5 months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p < 0.01). Malnutrition was found in 25% COVID-19 survivors over 65 years of age compared to 21% younger participants (p < 0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19.

DISCUSSION: In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5 months from acute illness.

CONCLUSIONS: Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients.}, } @article {pmid37665505, year = {2023}, author = {Adly, HM and Saleh, SAK and Garout, MA and Abdulkhaliq, AA and Khafagy, AA and Saati, AA and AlJahdali, IA and Alandiyjany, MN and Al-Tawfiq, JA}, title = {Post COVID-19 Symptoms Among Infected Vaccinated Individuals: A Cross-Sectional Study in Saudi Arabia.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {4}, pages = {740-750}, pmid = {37665505}, issn = {2210-6014}, support = {IFP22UQU4240001DSR010//Ministry of Education - Kingdom of Saudi Arabi/ ; }, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Cross-Sectional Studies ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Saudi Arabia/epidemiology ; }, abstract = {INTRODUCTION: Multiple studies investigated the endurance and occurrence of symptoms three months after SARS-CoV-2 infection. This study examines the possible effects of COVID-19 vaccination on the persistence of post-recovery symptoms.

PATIENTS AND METHODS: A cross-sectional survey was conducted in Saudi Arabia to evaluate 14 prevalent long COVID-19 symptoms among vaccinated individuals. Patients self-reported their acute COVID-19 experience, demographic information, chronic conditions, vaccine history, and persistent symptoms.

RESULTS: Of the 484 patients, four respondents were excluded from the study as they had not received the vaccine, and 111 (23.1%) were vaccinated but did not get infected and were also excluded. The remaining 369 (76.9%) reported COVID-19 and a vaccination and thus they were included in the study. The occurrence of post-COVID-19 symptoms was reported in 59 (16.1%) for ≤ 3 months, 202 (54.8%) experienced persistent symptoms 3-6 months, and 108 (29.1%) reported symptoms lasting > 6 months. In relation to age group, persistent symptoms 3-6 months after recovery was more common in those > 50 years and symptoms lasting > 6 months were more common in 30-50 years of age (p < 0.001). Persistence of symptoms for  3-6 months was more common in those who were infected prior to vaccination compared to those who were infected after vaccination (P < 0.001). Of the included patients, 323 (87.5%) rated their health as good, 41 (11.1%) considered it fair, and 5 (1.4%) described their well-being as poor or terrible.

CONCLUSION: The study provides information of persistent symptoms in vaccinated individuals who had recovered from COVID-19 and highlights the need for targeted interventions to alleviate post-COVID-19 symptoms. The study is limited by its reliance on self-reported data and potential selection bias. Future research is needed to understand the mechanisms underlying persistent symptoms in vaccinated individuals and to identify effective interventions for long COVID.}, } @article {pmid37665495, year = {2023}, author = {Gómez-Dabó, L and Melgarejo-Martínez, L and Caronna, E and Pozo-Rosich, P}, title = {Headache in COVID-19 and Long COVID: to Know Facts for Clinical Practice.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {10}, pages = {551-560}, pmid = {37665495}, issn = {1534-6293}, abstract = {PURPOSE OF REVIEW: Headache is one of the most frequent symptoms of the acute and post-acute phase of COVID-19. Specific epidemiology, clinical features, risk factors, pathophysiology, and treatment have been reported in these two scenarios. With this narrative review of the literature, we aim to provide updated knowledge on headache in the COVID-19 setting and give clinicians a practical approach on this topic to guide them in their clinical practice.

RECENT FINDINGS: Headache mechanisms in COVID-19 are still poorly understood. Strong evidence is also lacking on how to best treat and manage these patients, especially those with persistent and disabling headache after COVID-19. Data are also scarce on the characteristics of headache in COVID-19 caused by the new SARS-CoV-2 (Omicron) variants and how these may influence the acute and persistent symptoms of COVID-19. Patients with pre-existing primary headache disorders remain a particularly concerning population due to their biological predisposition in suffering from headaches and the potential risk of worsening in the setting of SARS-CoV-2 infection. Although there is an exponential growth of scientific evidence, studies are often controversial and focused on the first wave of the pandemic, making COVID-19 headache still a challenging matter for clinicians. New research is therefore needed.}, } @article {pmid37665487, year = {2023}, author = {Erol, M and Tezcan, H and Duran, M and Uygun, T and Kurtipek, E and Önner, H}, title = {The role of myocardial perfusion imaging in predicting myocardial ischemia in patients diagnosed with long COVID.}, journal = {The international journal of cardiovascular imaging}, volume = {39}, number = {11}, pages = {2279-2284}, pmid = {37665487}, issn = {1875-8312}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Myocardial Perfusion Imaging/methods ; Predictive Value of Tests ; *COVID-19/complications ; *Coronary Artery Disease/complications ; *Myocardial Ischemia/etiology/complications ; Tomography, Emission-Computed, Single-Photon/methods ; Coronary Angiography/methods ; Ischemia/complications ; }, abstract = {OBJECTIVE: Incomplete recovery with long-term complications weeks beyond the acute coronavirus disease 2019 (COVID-19) infection is referred to as long COVID. Among the well-known long-term complications of COVID-19, myocardial damage is a frequently encountered side effect. Yet there is a lack of data for identifying high-risk patients who are more likely to develop long-term cardiovascular complications following COVID-19. Myocardial perfusion imaging (MPI) is the primary functional imaging modality in evaluating myocardial ischemia This study aimed to investigate the role of MPI in predicting myocardial ischemia in patients diagnosed with long COVID.

METHODS: Subjects were selected from eligible long COVID patients and control subjects without a prior history of COVID-19 who were referred to the nuclear medicine department for stress and rest single-photon emission computed tomography (SPECT) MPI. All participants' past medical records and clinical, and demographic characteristics were scanned. In addition, patients undergoing coronary angiography (CAG) following SPECT MPI were documented and patients with critical coronary stenosis were identified.

RESULTS: Our results revealed that long COVID patients had higher rates of abnormal summed stress scores compared to the control subjects (p < 0.05). Additionally, serum CRP level, SPECT lung-to-heart ratio (LHR), and the presence of long COVID were independent predictors of ischemia. The presence of long COVID was the best predictor of ischemia among the aforementioned parameters (p < 0.001).

CONCLUSION: Our data indicate that SPECT MPI provides comprehensive information on myocardial perfusion and left ventricular function in long COVID patients.}, } @article {pmid37665334, year = {2023}, author = {Sivan, M and Rocha Lawrence, R and O'Brien, P}, title = {Digital Patient Reported Outcome Measures Platform for Post-COVID-19 Condition and Other Long-Term Conditions: User-Centered Development and Technical Description.}, journal = {JMIR human factors}, volume = {10}, number = {}, pages = {e48632}, pmid = {37665334}, issn = {2292-9495}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Patient Reported Outcome Measures ; }, abstract = {BACKGROUND: Post-COVID-19 condition (PCC), colloquially known as long COVID, is a multisystem condition characterized by persistent symptoms beyond 4 weeks after the SARS-CoV-2 infection. More than 60 million people with PCC worldwide need prompt assessment, diagnosis, and monitoring, with many requiring specialist help from a multidisciplinary team of health care professionals (HCPs). Consequently, a scalable digital system is required for both people with PCC and HCPs to capture the breadth of symptoms and their impact on health, using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs).

OBJECTIVE: We aim to develop and implement a novel PCC digital PROM (DPROM) platform for (1) securely collecting PROM and PREM data from people with PCC, (2) enabling users to monitor symptoms longitudinally and assess response to treatment, (3) generating reports for the electronic health records (EHRs), (4) providing summary reports on PCC services based on national requirements, and (5) facilitating the sharing of relevant data with authorized research teams to accelerate our understanding of this new condition and evaluate new strategies to manage PCC.

METHODS: We (1) undertook requirement analysis with people with PCC, HCPs, and researchers to identify the needs of the DPROM platform and determine its required functionalities; (2) designed and developed a clinically useful web portal for staff and a mobile app for patients, with a web-based alternative app to improve patient and staff choice, limit the risk of digital exclusion, and account for variability across services; (3) determined the PROMs and PREMs that PCC services would prefer to use on the platform; and (4) designed the summary report function that can be generated for each user for the EHR and for reporting to national health authorities.

RESULTS: A DPROM platform to record PCC symptom profile, condition severity, functional disability, and quality of life, based on the C19-YRS (Yorkshire Rehabilitation Scale) and other PROMs and PREMs, was developed. Individual-level medical information and details on the COVID-19 illness can be captured systematically. The platform generates easy-to-understand scores, radar plots and line graphs for people with PCC to self-monitor their condition and for HCPs to assess the natural course of the condition and the response to interventions. Clinics can configure a suite of PROMs and PREMs based on their local and national service and commissioning requirements and support research studies which require large-scale data collection on PROMs. The DPROM platform enables automatic aggregate data analysis for services to undertake service evaluation and cost-effectiveness analysis. The DPROM platform generated summary report can be uploaded to the EHRs of people with PCC.

CONCLUSIONS: A multifunctional DPROM platform to assess, grade, and monitor PCC has been developed. Future research will analyze the system's usability in specialist PCC clinical services and other long-term conditions.}, } @article {pmid37663849, year = {2023}, author = {Ayadi, H and Bour, C and Fischer, A and Ghoniem, M and Fagherazzi, G}, title = {The Long COVID experience from a patient's perspective: a clustering analysis of 27,216 Reddit posts.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1227807}, pmid = {37663849}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cluster Analysis ; Fatigue ; Pain ; }, abstract = {OBJECTIVE: This work aims to study the profiles of Long COVID from the perspective of the patients spontaneously sharing their experiences and symptoms on Reddit.

METHODS: We collected 27,216 posts shared between July 2020 and July 2022 on Long COVID-related Reddit forums. Natural language processing, clustering techniques and a Long COVID symptoms lexicon were used to extract the different symptoms and categories of symptoms and to study the co-occurrences and correlation between them.

RESULTS: More than 78% of the posts mentioned at least one Long COVID symptom. Fatigue (29.4%), pain (22%), clouded consciousness (19.1%), anxiety (17.7%) and headaches (15.6%) were the most prevalent symptoms. They also highly co-occurred with a variety of other symptoms (e.g., fever, sinonasal congestion). Different categories of symptoms were found: general (45.5%), neurological/ocular (42.9%), mental health/psychological/behavioral (35.2%), body pain/mobility (35.1%) and cardiorespiratory (31.2%). Posts focusing on other concerns of the community such as vaccine, recovery and relapse and, symptom triggers were detected.

CONCLUSIONS: We demonstrated the benefits of leveraging large volumes of data from Reddit to characterize the heterogeneity of Long COVID profiles. General symptoms, particularly fatigue, have been reported to be the most prevalent and frequently co-occurred with other symptoms. Other concerns, such as vaccination and relapse following recovery, were also addressed by the Long COVID community.}, } @article {pmid37663602, year = {2023}, author = {Yuan, K and Bao, Y and Leng, Y and Li, X}, title = {Editorial: The acute and long-term impact of COVID-19 on mental health of children and adolescents.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1265934}, pmid = {37663602}, issn = {1664-0640}, } @article {pmid37661673, year = {2023}, author = {Cem, E and Kıymet, E and Böncüoğlu, E and Şahinkaya, Ş and Çelebi, MY and Gülderen, M and Kara, AA and Özenen, GG and Bayram, N and Devrim, İ}, title = {Rehospitalization indications of children hospitalized for COVID-19 infections after discharge: Should we suspect long COVID?.}, journal = {The Turkish journal of pediatrics}, volume = {65}, number = {4}, pages = {583-591}, doi = {10.24953/turkjped.2022.829}, pmid = {37661673}, issn = {2791-6421}, mesh = {Humans ; Child ; Female ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Patient Readmission ; Patient Discharge ; Retrospective Studies ; }, abstract = {BACKGROUND: Complications that may develop in children after coronavirus disease 2019 (COVID-19) infections are unknown. The `Long COVID` syndrome is a new process that can also be identified in children. Therefore, in this study, the conditions that may develop in children after COVID-19 infection were discussed, and the indications for rehospitalizations were reviewed.

METHODS: This retrospective cohort study was conducted in a tertiary children`s hospital in İzmir, Türkiye. All children who were rehospitalized in the study center after discharge, and the indications for readmissions were screened.

RESULTS: Since the beginning of the pandemic, 777 children with COVID-19 infection were hospitalized, including 98 (12.6%) cases rehospitalized for any indication. Fifty-five (56.1%) patients were male, and 43 (43.9%) were female. The mean age of the study population was 79.3±63.5 months (1 month to 17 years). Among these 98 patients, 76 (77.6%) were rehospitalized because of the presence of their primary underlying disease, nonspecific infectious diseases unrelated to COVID-19, and the need to perform certain surgical procedures. The remaining 22 (22.4%) patients presented with symptoms such as fatigue, fever, abdominal pain, and myalgia after the COVID-19 infection. No other underlying cause was detected in approximately one-third of the patients, whose manifestations were found to be consistent with long COVID syndrome.

CONCLUSIONS: The findings of acute COVID-19 infection are well characterized, but there is still limited data on its long-term outcomes. The majority of the study population that had no underlying disease were thought to have complications from the COVID-19 infection. Therefore, although the incidence rate of long COVID syndrome in childhood has not been revealed so far, it should be kept in mind among relevant differential diagnoses.}, } @article {pmid37658773, year = {2023}, author = {Espinoza-Bravo, C and Arnal-Gómez, A and Martínez-Arnau, FM and Núñez-Cortés, R and Hernández-Guillén, D and Flor-Rufino, C and Cortés-Amador, S}, title = {Effectiveness of Functional or Aerobic Exercise Combined With Breathing Techniques in Telerehabilitation for Patients With Long COVID: A Randomized Controlled Trial.}, journal = {Physical therapy}, volume = {103}, number = {11}, pages = {}, doi = {10.1093/ptj/pzad118}, pmid = {37658773}, issn = {1538-6724}, mesh = {Adult ; Humans ; *COVID-19 ; Exercise ; Exercise Therapy/methods ; Fatigue ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Telerehabilitation/methods ; Middle Aged ; }, abstract = {OBJECTIVE: The aim of this study was to compare the short-term clinical effects of 2 telerehabilitation programs, functional versus aerobic exercises (AEs), both combined with breathing techniques, regarding the improvement of long coronavirus disease 2019 (COVID-19) symptoms.

METHODS: A randomized controlled trial was conducted. The participants were assigned randomly to either the functional exercise (FE) group or AE group, both including breathing techniques. The interventions lasted for 8 weeks with 3 sessions per week, and they were conducted through the Fisiotrack mobile phone application. Assessments were performed at baseline and after treatment, including testing fatigue (Fatigue Assessment Scale), dyspnea (London Chest Activity of Daily Living Scale), functional performance (30 Seconds Standing Test), perceived stress (Perceived Stress Scale), anxiety and depression (Hospital Anxiety and Depression Questionnaire), and quality of life (European Quality of Life Scale). The perceived change after treatment (Patient Global Impression of Change Scale), the usability of the application (System Usability Scale), and the adherence to treatment were also examined after treatment.

RESULTS: In total, 43 participants (FE group, n = 21; AE group, n = 22; mean age = 42.4 [SD = 6.5] years) completed the study. In the intragroup comparison, the FE group showed improved fatigue (-6.7 points; 95% CI = -11.9 to -1.3), functional capacity (2.6 repetitions; 95% CI = 0.3 to 4.9), and perceived stress (-4.9 points; 95% CI = -9.1 to 0.8), while the AE group showed improved perceived stress (-6.2 points; 95% CI = -10.3 to -2.1). No significant differences in the intergroup effect were identified for the studied variables. Significant differences were observed in the Patient Global Impression of Change Scale in favor of the FE group compared to the AE group, and quality of life reached the minimal clinically important difference for both groups. The ease of use of the telerehabilitation tool was rated excellent in both groups.

CONCLUSIONS: Both telerehabilitation exercise modalities are effective at improving stress symptoms and quality of life in patients with long COVID-19. For improving fatigue and functional performance, FE shows more promising results.

IMPACT: FE or AE may be recommended depending on patients' symptoms, and both may improve quality of life and stress symptoms in patients with long COVID-19. Telerehabilitation may be an optimal intervention modality for the prescription of physical exercise in patients with long COVID-19.}, } @article {pmid37657964, year = {2023}, author = {Zhao, S and Toniolo, S and Hampshire, A and Husain, M}, title = {Effects of COVID-19 on cognition and brain health.}, journal = {Trends in cognitive sciences}, volume = {27}, number = {11}, pages = {1053-1067}, pmid = {37657964}, issn = {1879-307X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Brain/diagnostic imaging ; Cognition ; Neuroimaging ; }, abstract = {COVID-19 is associated with a range of neurological, cognitive, and mental health symptoms both acutely and chronically that can persist for many months after infection in people with long-COVID syndrome. Investigations of cognitive function and neuroimaging have begun to elucidate the nature of some of these symptoms. They reveal that, although cognitive deficits may be related to brain imaging abnormalities in some people, symptoms can also occur in the absence of objective cognitive deficits or neuroimaging changes. Furthermore, cognitive impairment may be detected even in asymptomatic individuals. We consider the evidence regarding symptoms, cognitive deficits, and neuroimaging, as well as their possible underlying mechanisms.}, } @article {pmid37655303, year = {2023}, author = {Joffe, AR and Elliott, A}, title = {Long COVID as a functional somatic symptom disorder caused by abnormally precise prior expectations during Bayesian perceptual processing: A new hypothesis and implications for pandemic response.}, journal = {SAGE open medicine}, volume = {11}, number = {}, pages = {20503121231194400}, pmid = {37655303}, issn = {2050-3121}, abstract = {This review proposes a model of Long-COVID where the constellation of symptoms are in fact genuinely experienced persistent physical symptoms that are usually functional in nature and therefore potentially reversible, that is, Long-COVID is a somatic symptom disorder. First, we describe what is currently known about Long-COVID in children and adults. Second, we examine reported "Long-Pandemic" effects that create a risk for similar somatic symptoms to develop in non-COVID-19 patients. Third, we describe what was known about somatization and somatic symptom disorder before the COVID-19 pandemic, and suggest that by analogy, Long-COVID may best be conceptualized as one of these disorders, with similar symptoms and predisposing, precipitating, and perpetuating factors. Fourth, we review the phenomenon of mass sociogenic (functional) illness, and the concept of nocebo effects, and suggest that by analogy, Long-COVID is compatible with these descriptions. Fifth, we describe the current theoretical model of the mechanism underlying functional disorders, the Bayesian predictive coding model for perception. This model accounts for moderators that can make symptom inferences functionally inaccurate and therefore can explain how to understand common predisposing, precipitating, and perpetuating factors. Finally, we discuss the implications of this framework for improved public health messaging during a pandemic, with recommendations for the management of Long-COVID symptoms in healthcare systems. We argue that the current public health approach has induced fear of Long-COVID in the population, including from constant messaging about disabling symptoms of Long-COVID and theorizing irreversible tissue damage as the cause of Long-COVID. This has created a self-fulfilling prophecy by inducing the very predisposing, precipitating, and perpetuating factors for the syndrome. Finally, we introduce the term "Pandemic-Response Syndrome" to describe what previously was labeled Long-COVID. This alternative perspective aims to stimulate research and serve as a lesson learned to avoid a repeat performance in the future.}, } @article {pmid37654836, year = {2022}, author = {Chiappelli, F and Fotovat, L}, title = {Post acute CoViD-19 syndrome (PACS) - Long CoViD.}, journal = {Bioinformation}, volume = {18}, number = {10}, pages = {908-911}, pmid = {37654836}, issn = {0973-2063}, abstract = {Patients sero-positive for the Systemic Acute Respiratory Syndrome Corona virus2 (SARS-CoV2) virus develop the Corona Virus Disease 2019 (CoViD-19). CoViD-19 may be asymptomatic in some individuals, proffer mild symptoms in other patients, and can be a serious and even lethal disease in a sub-group of the population. The variables that determine the severity of CoViD-19 have not been fully characterized. What is clear is that the patients who survive CoViD-19 return to a state of sero-negativity for SARS-CoV2 generally within 3-5 weeks. However, several cases of repeated infection have been reported, and a large proportion of CoViD-19-recovered patients manifest multi-system and multi-organ symptomatic pathologies several weeks-to-months after resuming sero-negativity for SARS-CoV2. This new pathological condition, originally termed Long Covid, is now recognized as the Post Acute CoViD-19 Syndrome (PACS). The original principal clusters of signs and symptoms of PACS: likelihood of relapse and reinfection, physical fatigue and cognitive slowdown, may actually be broadened to include immune deregulation, cardiovascular disease and coagulation abnormalities. The development and evaluation of new and improved clinical interventions for PACS are critical and timely.}, } @article {pmid37654669, year = {2023}, author = {Cheetham, NJ and Penfold, R and Giunchiglia, V and Bowyer, V and Sudre, CH and Canas, LS and Deng, J and Murray, B and Kerfoot, E and Antonelli, M and Rjoob, K and Molteni, E and Österdahl, MF and Harvey, NR and Trender, WR and Malim, MH and Doores, KJ and Hellyer, PJ and Modat, M and Hammers, A and Ourselin, S and Duncan, EL and Hampshire, A and Steves, CJ}, title = {The effects of COVID-19 on cognitive performance in a community-based cohort: a COVID symptom study biobank prospective cohort study.}, journal = {EClinicalMedicine}, volume = {62}, number = {}, pages = {102086}, pmid = {37654669}, issn = {2589-5370}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/W005611/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Cognitive impairment has been reported after many types of infection, including SARS-CoV-2. Whether deficits following SARS-CoV-2 improve over time is unclear. Studies to date have focused on hospitalised individuals with up to a year follow-up. The presence, magnitude, persistence and correlations of effects in community-based cases remain relatively unexplored.

METHODS: Cognitive performance (working memory, attention, reasoning, motor control) was assessed in a prospective cohort study of participants from the United Kingdom COVID Symptom Study Biobank between July 12, 2021 and August 27, 2021 (Round 1), and between April 28, 2022 and June 21, 2022 (Round 2). Participants, recruited from the COVID Symptom Study smartphone app, comprised individuals with and without SARS-CoV-2 infection and varying symptom duration. Effects of COVID-19 exposures on cognitive accuracy and reaction time scores were estimated using multivariable ordinary least squares linear regression models weighted for inverse probability of participation, adjusting for potential confounders and mediators. The role of ongoing symptoms after COVID-19 infection was examined stratifying for self-perceived recovery. Longitudinal analysis assessed change in cognitive performance between rounds.

FINDINGS: 3335 individuals completed Round 1, of whom 1768 also completed Round 2. At Round 1, individuals with previous positive SARS-CoV-2 tests had lower cognitive accuracy (N = 1737, β = -0.14 standard deviations, SDs, 95% confidence intervals, CI: -0.21, -0.07) than negative controls. Deficits were largest for positive individuals with ≥12 weeks of symptoms (N = 495, β = -0.22 SDs, 95% CI: -0.35, -0.09). Effects were comparable to hospital presentation during illness (N = 281, β = -0.31 SDs, 95% CI: -0.44, -0.18), and 10 years age difference (60-70 years vs. 50-60 years, β = -0.21 SDs, 95% CI: -0.30, -0.13) in the whole study population. Stratification by self-reported recovery revealed that deficits were only detectable in SARS-CoV-2 positive individuals who did not feel recovered from COVID-19, whereas individuals who reported full recovery showed no deficits. Longitudinal analysis showed no evidence of cognitive change over time, suggesting that cognitive deficits for affected individuals persisted at almost 2 years since initial infection.

INTERPRETATION: Cognitive deficits following SARS-CoV-2 infection were detectable nearly two years post infection, and largest for individuals with longer symptom durations, ongoing symptoms, and/or more severe infection. However, no such deficits were detected in individuals who reported full recovery from COVID-19. Further work is needed to monitor and develop understanding of recovery mechanisms for those with ongoing symptoms.

FUNDING: Chronic Disease Research Foundation, Wellcome Trust, National Institute for Health and Care Research, Medical Research Council, British Heart Foundation, Alzheimer's Society, European Union, COVID-19 Driver Relief Fund, French National Research Agency.}, } @article {pmid37653608, year = {2023}, author = {Xu, J and Lodge, T and Kingdon, C and Strong, JWL and Maclennan, J and Lacerda, E and Kujawski, S and Zalewski, P and Huang, WE and Morten, KJ}, title = {Developing a Blood Cell-Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {10}, number = {30}, pages = {e2302146}, pmid = {37653608}, issn = {2198-3844}, support = {R01 AI103629/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/genetics ; Leukocytes, Mononuclear ; Artificial Intelligence ; Post-Acute COVID-19 Syndrome ; Diagnostic Tests, Routine ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by debilitating fatigue that profoundly impacts patients' lives. Diagnosis of ME/CFS remains challenging, with most patients relying on self-report, questionnaires, and subjective measures to receive a diagnosis, and many never receiving a clear diagnosis at all. In this study, a single-cell Raman platform and artificial intelligence are utilized to analyze blood cells from 98 human subjects, including 61 ME/CFS patients of varying disease severity and 37 healthy and disease controls. These results demonstrate that Raman profiles of blood cells can distinguish between healthy individuals, disease controls, and ME/CFS patients with high accuracy (91%), and can further differentiate between mild, moderate, and severe ME/CFS patients (84%). Additionally, specific Raman peaks that correlate with ME/CFS phenotypes and have the potential to provide insights into biological changes and support the development of new therapeutics are identified. This study presents a promising approach for aiding in the diagnosis and management of ME/CFS and can be extended to other unexplained chronic diseases such as long COVID and post-treatment Lyme disease syndrome, which share many of the same symptoms as ME/CFS.}, } @article {pmid37652756, year = {2024}, author = {Rigo, S and Barbic, F and Khalaf, K and Bisoglio, A and Pani, M and Minonzio, M and Rinaldi, L and Ciccarelli, M and Bordoni, MG and Verzeletti, P and Badilini, F and Bonovas, S and Piovani, D and Shiffer, D and Furlan, R}, title = {The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study.}, journal = {European journal of internal medicine}, volume = {120}, number = {}, pages = {38-45}, doi = {10.1016/j.ejim.2023.08.018}, pmid = {37652756}, issn = {1879-0828}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Prospective Studies ; Quality of Life ; *Orthostatic Intolerance ; SARS-CoV-2 ; Fatigue/etiology ; Pain ; }, abstract = {Long-COVID syndrome is characterized by fatigue, orthostatic intolerance, tachycardia, pain, memory difficulties, and brain fog, which may be associated with autonomic nervous system abnormalities. We aimed to evaluate the short and long-term course of COVID-19 autonomic symptoms and quality of life (QoL) after SARS-CoV-2 infection through a one-year follow-up combined with validated questionnaires. Additionally, we aimed to identify patients with worsening autonomic symptoms at 6 and 12 months by dividing the patient cohort into two sub-groups: the Post-COVID healed Control sub-group (total score<16.4) and the Long-COVID autonomic syndrome sub-group (total score>16.4). This prospective cohort studied 112 SARS-CoV-2 positive patients discharged from Humanitas Research Hospital between January and March 2021. Autonomic symptoms and QoL were assessed using the composite autonomic symptom scale 31 (COMPASS-31) and Short Form Health Survey (SF-36) questionnaires at various time points: before SARS-CoV-2 infection (PRE), at hospital discharge (T0), and at 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months of follow-up. COMPASS-31 total score, Orthostatic Intolerance and Gastrointestinal function indices, QoL, physical functioning, pain, and fatigue scores worsened at T0 compared to PRE but progressively improved at T1 and T3, reflecting the acute phase of COVID-19. Unexpectedly, these indices worsened at T6 and T12 compared to T3. Subgroup analysis revealed that 47% of patients experienced worsening autonomic symptoms at T6 and T12, indicating Long-COVID autonomic syndrome. Early rehabilitative and pharmacological therapy is recommended for patients at the T1 and T3 stages after SARS-CoV-2 infection to minimize the risk of developing long-term autonomic syndrome.}, } @article {pmid37652731, year = {2023}, author = {van der Feltz-Cornelis, C and Attree, E and Heightman, M and Gabbay, M and Allsopp, G}, title = {Integrated care pathways: a new approach for integrated care systems.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {73}, number = {734}, pages = {422}, pmid = {37652731}, issn = {1478-5242}, mesh = {Humans ; *Delivery of Health Care, Integrated ; }, } @article {pmid37652474, year = {2023}, author = {Moldovan, AF and Moga, I and Moga, T and Ghitea, EC and Babes, K and Ghitea, TC}, title = {Assessing the Risk of Stroke in the Elderly in the Context of Long-COVID, Followed Through the Lens of Family Medicine.}, journal = {In vivo (Athens, Greece)}, volume = {37}, number = {5}, pages = {2284-2295}, pmid = {37652474}, issn = {1791-7549}, mesh = {Humans ; Aged ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Family Practice ; *Stroke/epidemiology/etiology ; Seizures ; }, abstract = {BACKGROUND/AIM: Patients infected with COVID-19 may experience a range of acute and chronic neurological disorders. While severe neurological complications like strokes and seizures were less common during the acute or post-COVID period, the long-term effects of COVID-19, known as long COVID, have received limited attention. This study aimed to examine the lasting consequences of SARS-CoV-2 infection and establish potential connections with related diseases.

PATIENTS AND METHODS: We followed a group of 157 patients for one year, predominantly from urban areas (61.8%), divided into three groups based on the presence of associated diseases that pose health risks: the control (43 patients), low-risk (67 patients), and high-risk (47 patients) groups.

RESULTS: We observed an inverse relationship between oxygen saturation and erythrocyte sedimentation rate, as well as a direct relationship between varicose disease and dyslipidemia, and gastrointestinal disease. Additionally, we noticed a less significant improvement in oxygen saturation and increased prevalence of psychoanxiety disorders in individuals undergoing anticoagulant treatment.

CONCLUSION: The impact of long COVID and its secondary effects, which persist for an extended period and are influenced by associated diseases, can be effectively monitored and addressed by primary care physicians. These findings can serve as a basis for developing more efficient approaches to managing the long-term consequences of COVID-19.}, } @article {pmid37652071, year = {2023}, author = {Jassat, W and Reyes, LF and Munblit, D and Caoili, J and Bozza, F and Hashmi, M and Edelstein, M and Cohen, C and Alvarez-Moreno, CA and Cao, B}, title = {Long COVID in low-income and middle-income countries: the hidden public health crisis.}, journal = {Lancet (London, England)}, volume = {402}, number = {10408}, pages = {1115-1117}, doi = {10.1016/S0140-6736(23)01685-9}, pmid = {37652071}, issn = {1474-547X}, mesh = {Humans ; *COVID-19/epidemiology ; Public Health ; Post-Acute COVID-19 Syndrome ; Developing Countries ; Poverty ; }, } @article {pmid37651035, year = {2023}, author = {Harari, S and Mannucci, PM and Nobili, A and Galbussera, AA and Fortino, I and Leoni, O and Remuzzi, G and D'Avanzo, B and Tettamanti, M}, title = {Post-recovery impact of the second and third SARS-CoV-2 infection waves on healthcare resource utilization in Lombardy, Italy.}, journal = {Internal and emergency medicine}, volume = {18}, number = {7}, pages = {2011-2018}, pmid = {37651035}, issn = {1970-9366}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; SARS-CoV-2 ; Italy/epidemiology ; Delivery of Health Care ; Patient Acceptance of Health Care ; }, abstract = {The administrative claims database of the Italian region Lombardy, the first in Europe to be hit by the SARS-CoV-2 pandemic, was employed to evaluate the impact on healthcare resource utilization following recovery from the second (mainly alpha-related variant) and third (delta-related) infection waves. 317,164 individuals recovered from the infection and became negative after the second wave, 271,180 after the third. Of them, 1571 (0.5%) and 1575 (0.6%) died in the first 6 post-negativization months. In the remaining cases (315,593 after the second wave and 269,605 after the third), hospitalizations, attendances to emergency rooms and outpatient visits were compared with those recorded in the same pre-pandemic time periods in 2019. Dispensation of drugs as well as of imaging, and functional and biochemical diagnostic tests were also compared as additional proxies of the healthcare impact of the SARS-CoV-2 infection waves. Following both waves, hospitalizations, attendances at emergency rooms, and outpatient visits were similar in number and rates to the pre-pandemic periods. However, there was an increased dispensation a number of drugs and diagnostic tests, particularly those addressing the cardiorespiratory and blood systems. In a large region such as Lombardy taken as a relevant model because early and severely hit by the SARS-CoV-2 pandemic, the post-COVID burden on healthcare facilities was mildly relevant in cases who recovered from the second and third infection waves regarding such pivotal events as deaths, hospitalizations, and need for emergency room and outpatient visits, but was high regarding the dispensation of some drug classes and types of diagnostic tests.}, } @article {pmid37650258, year = {2023}, author = {Brogna, C and Cristoni, S and Marino, G and Montano, L and Viduto, V and Fabrowski, M and Lettieri, G and Piscopo, M}, title = {Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms.}, journal = {Proteomics. Clinical applications}, volume = {17}, number = {6}, pages = {e2300048}, doi = {10.1002/prca.202300048}, pmid = {37650258}, issn = {1862-8354}, mesh = {Humans ; *COVID-19 Vaccines ; SARS-CoV-2/genetics ; Proteomics ; Spike Glycoprotein, Coronavirus/genetics ; *COVID-19/prevention & control ; RNA, Messenger/genetics ; Vaccination ; }, abstract = {PURPOSE: The SARS-CoV-2 pandemic prompted the development and use of next-generation vaccines. Among these, mRNA-based vaccines consist of injectable solutions of mRNA encoding for a recombinant Spike, which is distinguishable from the wild-type protein due to specific amino acid variations introduced to maintain the protein in a prefused state. This work presents a proteomic approach to reveal the presence of recombinant Spike protein in vaccinated subjects regardless of antibody titer.

EXPERIMENTAL DESIGN: Mass spectrometry examination of biological samples was used to detect the presence of specific fragments of recombinant Spike protein in subjects who received mRNA-based vaccines.

RESULTS: The specific PP-Spike fragment was found in 50% of the biological samples analyzed, and its presence was independent of the SARS-CoV-2 IgG antibody titer. The minimum and maximum time at which PP-Spike was detected after vaccination was 69 and 187 days, respectively.

The presented method allows to evaluate the half-life of the Spike protein molecule "PP" and to consider the risks or benefits in continuing to administer additional booster doses of the SARS-CoV-2 mRNA vaccine. This approach is of valuable support to complement antibody level monitoring and represents the first proteomic detection of recombinant Spike in vaccinated subjects.}, } @article {pmid37650236, year = {2023}, author = {Evering, TH and Moser, CB and Jilg, N and Yeh, E and Sanusi, B and Wohl, DA and Daar, ES and Li, JZ and Klekotka, P and Javan, AC and Eron, JJ and Currier, JS and Hughes, MD and Smith, DM and Chew, KW and , }, title = {Long COVID After Bamlanivimab Treatment.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {Suppl 2}, pages = {S126-S135}, pmid = {37650236}, issn = {1537-6613}, support = {UM1 AI069423/AI/NIAID NIH HHS/United States ; UM1 AI069424/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; U01 AI069424/AI/NIAID NIH HHS/United States ; U01 AI068634/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; U01 AI068636/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; Male ; Middle Aged ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized/adverse effects ; *COVID-19 ; *Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Prospective evaluations of long COVID in outpatients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to determine the frequency and predictors of long COVID after treatment with the monoclonal antibody bamlanivimab in ACTIV-2/A5401.

METHODS: Data were analyzed from participants who received bamlanivimab 700 mg in ACTIV-2 from October 2020 to February 2021. Long COVID was defined as the presence of self-assessed COVID symptoms at week 24. Self-assessed return to pre-COVID health was also examined. Associations were assessed by regression models.

RESULTS: Among 506 participants, median age was 51 years. Half were female, 5% Black/African American, and 36% Hispanic/Latino. At 24 weeks, 18% reported long COVID and 15% had not returned to pre-COVID health. Smoking (adjusted risk ratio [aRR], 2.41 [95% confidence interval {CI}, 1.34- 4.32]), female sex (aRR, 1.91 [95% CI, 1.28-2.85]), non-Hispanic ethnicity (aRR, 1.92 [95% CI, 1.19-3.13]), and presence of symptoms 22-28 days posttreatment (aRR, 2.70 [95% CI, 1.63-4.46]) were associated with long COVID, but nasal severe acute respiratory syndrome coronavirus 2 RNA was not.

CONCLUSIONS: Long COVID occurred despite early, effective monoclonal antibody therapy and was associated with smoking, female sex, and non-Hispanic ethnicity, but not viral burden. The strong association between symptoms 22-28 days after treatment and long COVID suggests that processes of long COVID start early and may need early intervention.

CLINICAL TRIALS REGISTRATION: NCT04518410.}, } @article {pmid37648004, year = {2023}, author = {Duarte-Silva, M and Oliveira, CNS and Fuzo, C and Silva-Neto, PV and Toro, DM and Pimentel, VE and Pérez, MM and Fraga-Silva, TFC and Carvalho, JCS and Neto, FMS and Júnior, RBM and Arruda, E and Vilar, FC and Degiovani, AM and Ostini, FM and Feitosa, MR and Parra, RS and Gaspar, GG and Rocha, JJR and Feres, O and Fernandes, APM and Maruyama, SR and Russo, EMS and Bonato, VLD and Santos, IKFM and Sorgi, CA and Dias-Baruffi, M and Faccioli, LH and Cardoso, CRB and , }, title = {Divergent androgenic modulation of SARS-CoV-2 infection cooperates with dysregulated immune response to dictate worse COVID-19 outcomes in men.}, journal = {Brain, behavior, and immunity}, volume = {114}, number = {}, pages = {275-286}, doi = {10.1016/j.bbi.2023.08.026}, pmid = {37648004}, issn = {1090-2139}, abstract = {BACKGROUND: Sex-determined differences are rarely addressed in the management of diseases, despite well-known contrasting outcomes between female and male patients. In COVID-19 there is a remarkable disparity, with higher rates of mortality and more severe acute disease in men compared to women, who are mostly affected by long COVID-19. Furthermore, whether androgens play a protective or detrimental role in COVID-19 is still a matter of debate. Hence, the adequate management of the disease, especially regarding men presenting acute disease aggravation, still needs important data to elucidate the interplay between sex hormones and host immune responses that drive the worse evolution in male patients.

METHODS: A cohort of 92 controls and 198 non-severe and severe COVID-19 patients, from both sexes, was assessed for clinical outcomes, plasma steroids, gonadotropins, sex hormone binding globulin (SHBG) and immune mediators, before vaccination. These data were correlated with the global gene expression of blood leukocytes. The androgen receptor (AR) signaling pathway was investigated by transcriptomics and tracheal aspirate was obtained from severe patients for SARS-COV-2 quantification in the respiratory tract. The interplay among clinical, endocrine and immunological data deciphered the sex differences in COVID-19. Importantly, statistical analyses, using 95% confidence interval, considered confounding factors such as age and comorbidities, to definitely parse the role of androgens in the disease outcome.

RESULTS: There were notable contrasting levels of testosterone and dihydrotestosterone (DHT) throughout the disease course in male but not female patients. Inflammatory mediators presented significant negative correlations with testosterone, which was partially dependent on age and diabetes in men. Male subjects with severe COVID-19 had a significant up regulation of the AR signaling pathway, including modulation of TMPRSS2 and SRD5A1 genes, which are related to the viral infection and DHT production. Indeed, men had a higher viral load in the tracheal aspirate and levels of DHT were associated with increased relative risk of death. In contrast, the testosterone hormone, which was notably reduced in severe disease, was significantly related with susceptibility to COVID-19 worsening in male patients. Secondary hypogonadism was ruled out in the male severe COVID-19 subjects, as FSH, LH, and SHBG levels were not significantly altered. Instead, these subjects tended to have increased gonadotropin levels. Most interestingly, in this study we identified, for the first time, combined sets of clinical and immunoendocrine parameters that together predicted progression from non-severe to severe COVID-19 in men. One of the limitations of our study was the low or undetectable levels of DHT in many patients. Then, the evaluation of enzymes related to biosynthesis and signaling by androgens was mandatory and reiterated our findings.

CONCLUSIONS: These original results unraveled the disease immunoendocrine regulation, despite vaccination or comorbidities and pointed to the fundamental divergent role of the androgens testosterone and DHT in the determination of COVID-19 outcomes in men. Therefore, sex-specific management of the dysregulated responses, treatments or public health measures should be considered for the control of COVID-19 pandemic.}, } @article {pmid37646849, year = {2024}, author = {Shafiee, A and Seighali, N and Teymouri Athar, M and Abdollahi, AK and Jafarabady, K and Bakhtiyari, M}, title = {Levels of brain-derived neurotrophic factor (BDNF) among patients with COVID-19: a systematic review and meta-analysis.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {5}, pages = {1137-1152}, pmid = {37646849}, issn = {1433-8491}, mesh = {Humans ; *Brain-Derived Neurotrophic Factor/blood ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Many individuals have been suffering from consistent neurological and neuropsychiatric manifestations even after the remission of coronavirus disease (COVID-19). Brain-derived neurotrophic factor (BDNF) is a protein involved in the regulation of several processes, including neuroplasticity, neurogenesis, and neuronal differentiation, and has been linked to a range of neurological and psychiatric disorders. In this study, we aimed to synthesize the available evidence on the profile of BDNF in COVID-19. A comprehensive search was done in the Web of Science core collection, Scopus, and MEDLINE (PubMed), and Embase to identify relevant studies reporting the level of BDNF in patients with COVID-19 or those suffering from long COVID. We used the NEWCASTLE-OTTAWA tool for quality assessment. We pooled the effect sizes of individual studies using the random effect model for our meta-analysis. Fifteen articles were included in the systematic review. The sample sizes ranged from 16 to 183 participants. Six studies compared the level of BDNF in COVID-19 patients with healthy controls. The pooled estimate of the standardized mean difference in BDNF level between patients with COVID-19 and healthy individuals was - 0.84 (95% CI - 1.49 to - 0.18, p = 0.01, I2 = 81%) indicating a significantly lower BDNF level in patients with COVID-19. Seven studies assessed BDNF in different severity statuses of patients with COVID-19. The pooled estimate of the standardized mean difference in BDNF level was - 0.53 (95% CI - 0.85 to - 0.21, p = 0.001, I2 = 46%), indicating a significantly lower BDNF level in patients with more severe COVID-19. Three studies evaluated BDNF levels in COVID-19 patients through different follow-up periods. Only one study assessed the BDNF levels in long COVID patients. Sensitivity analyses did not alter the significance of the association. In this study, we showed a significant dysregulation of BDNF following COVID-19 infection. These findings may support the pathogenesis behind the long-lasting effects of this disease among infected patients. PROSPERO: CRD42023413536.}, } @article {pmid37646620, year = {2023}, author = {Edward, JA and Peruri, A and Rudofker, E and Shamapant, N and Parker, H and Cotter, R and Sabin, K and Lawley, J and Cornwell, WK}, title = {Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID.}, journal = {Journal of cardiopulmonary rehabilitation and prevention}, volume = {43}, number = {6}, pages = {400-406}, doi = {10.1097/HCR.0000000000000821}, pmid = {37646620}, issn = {1932-751X}, support = {K23 HL132048/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Exercise Therapy ; Exercise ; }, abstract = {The post-acute sequalae of SARS-CoV-2, also known as "Long COVID," is characterized by profound fatigue, impaired functional capacity with post-exertional malaise, orthostatic intolerance, and tachycardia. At least 25-30% of individuals impacted by SARS-CoV-2 will go on to experience the Long COVID syndrome, underscoring the detrimental impact this condition has on society. Although efforts are underway to further understand risk factors for Long COVID and identify strategies to prevent disease development entirely, implementation of treatment strategies is warranted to alleviate symptom burden among those affected. This review provides a rationale for exercise prescriptions tailored to the Long COVID patient based on the pathophysiology underlying this syndrome, as well as the previously demonstrated benefits of exercise training in other similar populations whose clinical manifestations result from cardiac deconditioning. Herein, we discuss methods to tailor exercise protocols, accommodating exercise intolerance and post-exertional malaise that may otherwise limit the ability to participate in a training protocol, as well as data demonstrating that a focused exercise prescription may effectively alleviate symptom burden in these patients. Long COVID results, in large part, from deconditioning, which may result from as little as 20 hr of inactivity. Exercise prescriptions tailored to patients with Long COVID may effectively alleviate symptom burden associated with this condition and in the absence of overt contraindications should be considered in management.}, } @article {pmid37646121, year = {2023}, author = {Gur, M and Manor, E and Hanna, M and Simaan, N and Gut, G and Toukan, Y and Hakim, F and Bar-Yoseph, R and Bentur, L}, title = {The effect of inspiratory muscle training in PCD and CF patients: A pilot study.}, journal = {Pediatric pulmonology}, volume = {58}, number = {11}, pages = {3264-3270}, doi = {10.1002/ppul.26655}, pmid = {37646121}, issn = {1099-0496}, mesh = {Humans ; Child ; Adolescent ; Young Adult ; Adult ; Pilot Projects ; Breathing Exercises ; *Cystic Fibrosis/therapy ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Respiratory Muscles ; Muscle Strength/physiology ; }, abstract = {BACKGROUND: Effective work of breathing and bronchial hygiene requires synergy of inspiratory and expiratory muscles. Inspiratory muscle training (IMT) is a part of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). There is some evidence of its efficacy in cystic fibrosis (CF) and, recently, in long COVID-19. We are not aware of studies on IMT in primary ciliary dyskinesia (PCD). Our aim was to assess the effect of IMT on respiratory muscle strength and pulmonary function in PCD and CF patients.

METHODS: A single center pilot study. Spirometry, lung clearance index (LCI), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured at baseline (visit 1), after a month of IMT with ®POWERbreathe (visit 2), and at follow-up (visit 3).

RESULTS: The cohort included 27 patients (19 PCD, 8 CF); mean age 18.4 ± 9.8 years. After a month of IMT, there was a significant increase in MIP and MIP% (6.19-7.44, p = .015; and 81.85%-100.41%, p = .046, respectively), which was sustained at visit 3. Compliance ≥90% led to higher improvement in MIP. In sub-group analysis, improvement in MIP and MIP% remained significant for PCD patients (p = .026 and p = .049, respectively). No significant changes were found in spirometry, MEP or LCI.

CONCLUSIONS: IMT was well-tolerated and led to improved inspiratory muscle strength in PCD patients. The clinical implication of improved MIP should be further investigated. Larger, long-term studies are needed to evaluate long-term effects of IMT on pulmonary function, respiratory muscle strength, pulmonary exacerbations, and quality of life.}, } @article {pmid37643641, year = {2023}, author = {Saad-Roy, CM and Morris, SE and Baker, RE and Farrar, J and Graham, AL and Levin, SA and Wagner, CE and Metcalf, CJE and Grenfell, BT}, title = {Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease.}, journal = {Journal of the Royal Society, Interface}, volume = {20}, number = {205}, pages = {20230247}, pmid = {37643641}, issn = {1742-5662}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chronic Disease ; Uncertainty ; }, abstract = {As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer-term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or 'evolution-proof') immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real-world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable and broadly protective vaccine.}, } @article {pmid37643476, year = {2023}, author = {M Oliveira, A and Ferreira Coelho, C and Lourenço, F and Campos Pinto, I and Atabão, J and Cabrita, R and Paraíso, R and Mesquita, E and Torrado, D and Marquez, P and Z Guerreiro, V}, title = {Long COVID Symptoms in Non-Hospitalised Patients: A Retrospective Study.}, journal = {Acta medica portuguesa}, volume = {36}, number = {10}, pages = {618-630}, doi = {10.20344/amp.19566}, pmid = {37643476}, issn = {1646-0758}, mesh = {Pregnancy ; Adult ; Humans ; Female ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Retrospective Studies ; Pandemics ; Quality of Life ; Fever ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has presented numerous challenges to healthcare systems. As the number of affected individuals continues to rise, it is crucial to find preventive, diagnostic, and therapeutic approaches. This study aims to describe different COVID-19 sequelae within a Primary Health Care population.

METHODS: A retrospective cohort study was conducted in adults diagnosed with COVID-19 from March 2020 to April 2022, excluding pregnant women, minors, nursing home residents, hospitalizations, and deaths. Data was gathered from surveillance records on the Trace COVID-19® platform, a pre-set original questionnaire (which included the Portuguese version of the World Health Organization's Quality of Life Assessment Instrument), and, if needed, patient electronic health records. Information on sociodemographic and clinical characteristics of acute COVID-19 was collected along with long COVID symptoms.

RESULTS: This study included 284 patients, aged 19 to 99 years old. The five most prevalent acute COVID-19 symptoms were fever (50.0%), tiredness (48.2%), myalgias (44.7%), dry cough (37.7%) and odynophagia (36.3%). Symptoms related to the neurological system (23.2%) and tiredness (22.9%) were the most prevalent in long COVID symptoms. Acute tiredness and arthralgia were associated with all long COVID outcomes. The associations between acute COVID-19 symptoms with long COVID outcomes were stronger for anosmia [OR = 5.07, 95% confidence interval (CI) 2.49 - 10.36, p < 0.001] on a neurological chapter, acute tiredness for long lasting tiredness (OR = 4.07, 95% CI 2.07 - 8.02, p = 0.041), fatigue for muscles and/or bones chapter (OR = 7.55, 95% CI 3.06 - 18.66, p < 0.001), tiredness on an endocrine/hormonal chapter (OR = 6.54, 95% CI 2.37 - 18.04, p < 0.001), dyspnea for respiratory symptoms (OR = 5.67, 95% CI 1.92 - 16.74, p = 0.002) and fever for stomach or intestine symptoms (OR = 8.06, 95% CI 2.55 - 25.47, p < 0.001). Almost all quality of life dimensions were negatively associated with the number of long COVID symptoms.

CONCLUSION: A higher number of acute symptoms, as well as the presence of specific COVID-19 symptoms were associated with reported symptoms ≥ 12 weeks after infection. In the studied population, an increased number of symptoms in both acute and long COVID had a significant negative impact on the perception of overall quality of life. The identification of these relationships could provide a new perspective for post-COVID care.}, } @article {pmid37638148, year = {2023}, author = {Gaber, TA}, title = {Pattern of Post COVID Fatigue in Elderly Patients.}, journal = {Advances in rehabilitation science and practice}, volume = {12}, number = {}, pages = {27536351231194561}, pmid = {37638148}, issn = {2753-6351}, abstract = {The incidence of Long COVID (LC) increases with age but then drops sharply in over 70-year-olds. The prevailing explanation is that different biases in data collection such as reluctance to report symptoms or attributing them to comorbidities may explain this pattern in this age group. Our local data suggested a similar pattern confirming the rarity of LC symptoms especially fatigue in the over 70s. Our data have also showed a different phenotype of post COVID fatigue which is not commonly associated with post exertional symptoms bringing into question the suggestion that bias in collecting data is the main cause. We explore several immunological, metabolic and epigenetic factors associated with aging that may explain such phenomenon.}, } @article {pmid37637608, year = {2023}, author = {Paruchuri, SSH and Farwa, UE and Jabeen, S and Pamecha, S and Shan, Z and Parekh, R and Lakkimsetti, M and Alamin, E and Sharma, V and Haider, S and Khan, J and Razzaq, W}, title = {Myocarditis and Myocardial Injury in Long COVID Syndrome: A Comprehensive Review of the Literature.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42444}, pmid = {37637608}, issn = {2168-8184}, abstract = {The repercussions of coronavirus disease 2019 (COVID-19) have been devastating on a global scale. Long COVID, which affects patients for weeks or even months after their initial infection, is not limited to individuals with severe symptoms and can affect people of all ages. The condition can impact various physiological systems, leading to chronic health conditions and long-term disabilities that present significant challenges for healthcare systems worldwide. This review explores the link between long COVID and cardiovascular complications such as myocardial injury and myocarditis. It also highlights the prevalence of these complications and identifies risk factors for their development in long COVID patients. Myocardial injury occurs due to direct cellular damage and T-cell-mediated cytotoxicity resulting in elevated cardiac biomarkers. Diagnostic techniques like electrocardiogram, troponin level testing, and magnetic resonance imaging can help identify myocarditis, but endomyocardial biopsy is considered the gold-standard diagnostic technique. Guideline-directed medical therapy is recommended for COVID-19 myocarditis patients for better prognosis while being monitored under comprehensive care management approaches. Therefore, it's critical to develop effective screening techniques specifically for vulnerable populations while conducting further research that addresses the effects of long COVID on society's physical health.}, } @article {pmid37637589, year = {2023}, author = {Dearing, E and Rempfer, E and Frasure, SE and Akselrod, H and Dobbs, JE and Poon, AN and Salazar, JE and Prajapati, D and Boniface, KS}, title = {Point-of-Care Ultrasound of Post-acute COVID-19 Syndrome: A Prospective Cohort Study.}, journal = {Cureus}, volume = {15}, number = {7}, pages = {e42569}, pmid = {37637589}, issn = {2168-8184}, abstract = {Introduction Acute COVID-19 patients can suffer from chronic symptoms known as post-acute sequelae of SARS-CoV-2 infection (PASC). Point-of-care ultrasound (POCUS) is established in acute COVID, but its utility in PASC is unclear. We sought to determine the incidence of cardiac and pulmonary abnormalities with POCUS in patients with PASC in a COVID-19 recovery clinic. Methods This prospective cohort study included adults (>18 years old) presenting with cardiopulmonary symptoms to the COVID-19 recovery clinic. A lung ultrasound and standard bedside echocardiogram were performed by ultrasound-trained physicians. Images were interpreted in real time by the performing sonographer and independently by a blinded ultrasound faculty member. Discrepancies in interpretation were addressed by consensus review. A modified Soldati score was calculated by the sum of the scores in each of the 12 lung zones, with each zone score ranging from 0 to 3 (maximum score of 36). The score was then compared to clinical outcomes and outpatient testing. Results Between April and July 2021, 41 patients received POCUS examinations, with 24 of those included in the study. In all, 15 out of 24 (62.5%) had a normal lung ultrasound. Of the nine subjects with lung abnormalities, the median modified Soldati score was 2. Three patients had trivial pericardial effusions, and all had normal left and right ventricular size and function. Conclusion The majority (62.5%) of patients presenting to the PASC clinic had a normal pulmonary ultrasound, and the vast majority (87.5%) had normal cardiac ultrasounds. These findings suggest that cardiopulmonary symptoms in PASC may be from etiologies not well evaluated by POCUS.}, } @article {pmid37633994, year = {2023}, author = {Juhász, V and Csulak, E and Szabó, L and Ocsovszky, Z and Balla, D and Nagy, G and Zorzi, A and Hoepelman, AIM and Merkely, B and Vágó, H and Sydó, N and , and , }, title = {Retrospective study of COVID-19 experiences in elite multinational aquatic athletes.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13978}, pmid = {37633994}, issn = {2045-2322}, mesh = {Female ; Humans ; *COVID-19/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Reinfection ; Athletes ; }, abstract = {This study assessed the experiences of elite aquatic athletes with coronavirus disease 2019 (COVID-19) during the first World Championship conducted without social distancing and an isolation "bubble". An online questionnaire was completed by 812 athletes (22.7 ± 5.9 years, 467 females) to provide data on demographics, sports activity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, symptoms, reinfection, vaccination status, and psychological aspects. The answers revealed that 49.4% of athletes had experienced SARS-CoV-2 infection. The infection rates varied significantly across different aquatic sports, with open water swimmers having the lowest (28%) and water polo players (67%) and artistic swimmers (61%) having the highest infection rates (p < 0.0001). The majority reported mild (51%) or moderate (27%) symptoms, while 16% remained asymptomatic. Reinfection occurred in 13%, and 10% of initial infections led to long COVID, with fatigue (65%) and shortness of breath (48%) being the most common long-term symptoms. Significantly, 92% of athletes received at least two vaccine doses and reported a positive vaccination experience (median score of 8 out of 10 for each shot). Mood changes and subjective performance drops significantly correlated with the overall experience scores (rho: 0.617, p < 0.0001, and rho: 0.466, p < 0.0001, respectively). In conclusion, most athletes experienced a benign disease course despite a relatively high infection rate. This study provides valuable insights into the COVID-19 experiences of elite aquatic athletes. The findings emphasize the importance of vaccination initiatives, monitoring psychological well-being and the need to fortify athletes' resilience in the face of future health challenges.}, } @article {pmid37633931, year = {2023}, author = {Vollrath, S and Matits, L and Schellenberg, J and Kirsten, J and Steinacker, JM and Bizjak, DA}, title = {Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {298}, pmid = {37633931}, issn = {2047-783X}, support = {070106/20-23//the Federal Institute of Sport Science of Germany/ ; }, mesh = {Humans ; Male ; Female ; *COVID-19 ; Lactic Acid ; Exercise ; Fatigue/etiology ; Physical Functional Performance ; }, abstract = {INTRODUCTION: Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise.

METHODS: A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS).

RESULTS: Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals.

CONCLUSION: Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion. Trial registration Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).}, } @article {pmid37632118, year = {2023}, author = {Đogaš, T and Novak, I and Babić, M and Vučković, M and Tandara, L and Radić, J}, title = {Associations of Serum Calprotectin, Arterial Stiffness and Long COVID Symptoms in Dalmatian Kidney Transplant Recipients.}, journal = {Viruses}, volume = {15}, number = {8}, pages = {}, pmid = {37632118}, issn = {1999-4915}, mesh = {Male ; Humans ; Middle Aged ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; Case-Control Studies ; Cross-Sectional Studies ; *Kidney Transplantation/adverse effects ; Quality of Life ; *Vascular Stiffness ; Leukocyte L1 Antigen Complex ; }, abstract = {We aimed to explore long COVID symptoms, serum calprotectin levels, and the parameters of arterial stiffness in Dalmatian kidney transplant recipients (KTRs) and their possible associations. A cross-sectional, single-center case-control study on 98 KTRs who had recovered from COVID-19 was performed. Long COVID symptoms were explored via standardized questionnaires assessing quality of life, and serum calprotectin was also measured. Out of 98 KTRs with a mean age of 62 years, 63 (64.3%) were men. Medical history, clinical and laboratory parameters, and arterial stiffness measurements were obtained for each study participant. Difficulties with mobility were present in 44.3% of the KTRs, while difficulties with self-care were present in 6.2%, difficulties with usual activities were demonstrated by 35.1%, pain in the extremities was present in 52.5%, and anxiety and depression were present in 26.8%. Our results showed significant differences regarding serum calprotectin levels in clinical manifestations of acute COVID-19 and follow-up laboratory parameters. The most significant positive predictors of the serum calprotectin value in the KTRs were respiratory insufficiency, acute kidney failure, the prescription of antihypertensives, leukocyte and neutrophil counts, the neutrophil/lymphocyte ratio and lactate dehydrogenase levels. Negative predictors were the time since COVID-19, high-density lipoprotein levels, kidney function parameters, and the lymphocyte count. To conclude, serum calprotectin has emerged as a possible promising biomarker for subclinical allograft rejection; however, further studies are needed to better understand this subject.}, } @article {pmid37631968, year = {2023}, author = {Hawkings, MJ and Vaselli, NM and Charalampopoulos, D and Brierley, L and Elliot, AJ and Buchan, I and Hungerford, D}, title = {A Systematic Review of the Prevalence of Persistent Gastrointestinal Symptoms and Incidence of New Gastrointestinal Illness after Acute SARS-CoV-2 Infection.}, journal = {Viruses}, volume = {15}, number = {8}, pages = {}, pmid = {37631968}, issn = {1999-4915}, support = {PDF-2018-11-ST2-006/DH_/Department of Health/United Kingdom ; NIHR-200910/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Incidence ; *COVID-19/complications/epidemiology ; Prevalence ; SARS-CoV-2 ; *Inflammatory Bowel Diseases ; }, abstract = {It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as 'post-COVID syndrome'. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.}, } @article {pmid37631966, year = {2023}, author = {Gumanova, NG and Gorshkov, AU and Bogdanova, NL and Korolev, AI}, title = {Effects of COVID-19 Infection in Healthy Subjects on Cardiac Function and Biomarkers of Oxygen Transport, Blood Coagulation and Inflammation.}, journal = {Viruses}, volume = {15}, number = {8}, pages = {}, pmid = {37631966}, issn = {1999-4915}, mesh = {Male ; Humans ; Female ; Healthy Volunteers ; *COVID-19 ; Cross-Sectional Studies ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Blood Coagulation ; Biomarkers ; Inflammation ; Immunoglobulin G ; Oxygen ; }, abstract = {BACKGROUND: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood.

METHODS: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8 ± 8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants.

RESULTS: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (p < 0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants.

CONCLUSIONS: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. Our observations contribute to the definition of vulnerabilities in the apparently healthy subjects with long COVID-19. These vulnerabilities may be more severe in patients with certain chronic diseases.}, } @article {pmid37631888, year = {2023}, author = {Bahadir, S and Kabacaoglu, E and Memis, KB and Hasan, HI and Aydin, S}, title = {The Effects of Vaccines on the Sequelae Rates of Recurrent Infections and the Severity of Pulmonary COVID-19 Infection by Imaging.}, journal = {Vaccines}, volume = {11}, number = {8}, pages = {}, pmid = {37631888}, issn = {2076-393X}, abstract = {Although vaccines have been shown to reduce the number of COVID-19 infection cases significantly, vaccine-related reactions, long COVID-19 syndrome, and COVID-19 infection following vaccination continue to be a burden on healthcare services and warrant further scientific research. The purpose of this study was to research the severity of pulmonary COVID-19 infection following vaccination and the sequelae rates of recurrent infections in vaccinated cases by imaging. Patients who underwent follow-up CTs at 1 month, 3 months, and 6 months in our hospital with a diagnosis of COVID-19 were scanned retrospectively. Furthermore, all essential information was gathered from patients' immunization records. The major findings of our study were: (1) sequelae were frequently observed in unvaccinated cases; (2) the correlation between vaccination status and the severity of sequelae was significant; (3) there was not any significant relationship between the vaccine type and the severity of sequelae; and (4) hematocrit, hemoglobin, and lymphocyte parameters may be used as predictors of sequelae rates. COVID-19 infection, although reduced in prevalence following the development of vaccines, still remains a public health concern because of reinfection. Vaccination not only appears to protect against primary infection, but also seems to reduce reinfection and sequalae rates following reinfection.}, } @article {pmid37629430, year = {2023}, author = {Kurys-Denis, E and Grzywa-Celińska, A and Podgórska, K and Kawa, MP}, title = {What Remains up to 7 Months after Severe and Moderate Pneumonia in Non-Vaccinated Patients with Long COVID? Results of a CT Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {16}, pages = {}, pmid = {37629430}, issn = {2077-0383}, abstract = {BACKGROUND: There is a growing evidence of long-lasting lung changes after COVID-19. Our aim was to assess the degree of lung injury and evaluate the recovery process of 4-7-month-non-vaccinated convalescent patients discharged from hospital after moderate and severe COVID-19 pneumonia, who presented with symptoms of long-COVID.

METHODS: On control lung CT after mean 5-month recovery period, we classified and determined the prevalence of residual radiological abnormalities in 39 symptomatic patients. To assess the advancement of the persisting changes we used the total severity score (TSS) and the chest CT score and then correlated the results with clinical data.

RESULTS AND CONCLUSIONS: On follow-up CT images, 94.9% of patients showed persistent radiological abnormalities. The most frequent changes were ground-glass opacities (74.4%), reticular pattern (64.1%), fibrotic changes (53.8%), nodules (33.3%), bronchiectasis (15.4%), vascular enlargement (10.3%), and cavitation (5.1%). The median TSS score was 4.1 points (interquartile range 3), whereas the median of the chest CT score 5.4 points (interquartile range of 4.5). No significant differences were observed between sex subgroups and between the severe and moderate course groups. There were no association between both CT scores and the severity of the initial disease, indicating that, mean 5 months after the disease, pulmonary abnormalities reduced to a similar stage in both subgroups of severity.}, } @article {pmid37629176, year = {2023}, author = {Bergantini, L and d'Alessandro, M and Gangi, S and Bianchi, F and Cameli, P and Perea, B and Meocci, M and Fabbri, G and Marrucci, S and Ederbali, M and Bargagli, E}, title = {Predictive Role of Cytokine and Adipokine Panel in Hospitalized COVID-19 Patients: Evaluation of Disease Severity, Survival and Lung Sequelae.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629176}, issn = {1422-0067}, mesh = {Humans ; *Cytokines ; Adipokines ; Interleukin-10 ; Tumor Necrosis Factor-alpha ; Post-Acute COVID-19 Syndrome ; Interleukin-4 ; Interleukin-6 ; *COVID-19 ; SARS-CoV-2 ; Patient Acuity ; Transforming Growth Factor beta ; }, abstract = {Coronavirus disease 2019 (COVID-19) may determine a multisystemic chronic syndrome after resolution of SARS-CoV-2 infection in a significant percentage of patients. Persistent cytokine dysregulation can contribute to long-lasting inflammation and tissue damage, resulting in the diverse, often debilitating symptoms experienced by some patients (so-called long COVID syndrome). The aim of our study was to evaluate the value of a panel of serum biomarkers of severity and prognosis in patients hospitalized for COVID-19 and also as predictive factors for the development of post-COVID lung sequelae after discharge from the hospital. All blood sampling was performed in the first 24 h after admission to the hospital. Serum analyte concentrations of IL-4, IL-2, CXCL10 (IP-10), IL-1β, TNF-α, CCL2 (MCP-1), IL-17A, IL-6, IL-10, IFN-γ, IL-12p70 and TGF-β1 were quantified by bead-based multiplex LEGENDplex™ analysis and commercially available ELISA kits. A total of 108 COVID-19 patients were enrolled in the study. Comparative analysis of these proteins showed higher levels of TGF-β and IL-6 and lower levels of RBP-4 and IL-10 in the severe group. Age, adiponectin, IL-8 and IL-32 resulted as the best predictors for survival. Moreover, IL-1β, IL17A, TNF-α, TGF-β, IL-4 and IL-6 were significantly higher in patients who showed HRCT evidence of fibrotic interstitial alterations at follow-up than patients who did not. The initial inflammatory status of patients on admission to the hospital with COVID-19, as reflected by the present panel of adipose tissue-related biomarkers and cytokines, offered insights into medium-term prognosis.}, } @article {pmid37629143, year = {2023}, author = {Boufidou, F and Medić, S and Lampropoulou, V and Siafakas, N and Tsakris, A and Anastassopoulou, C}, title = {SARS-CoV-2 Reinfections and Long COVID in the Post-Omicron Phase of the Pandemic.}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37629143}, issn = {1422-0067}, mesh = {Adolescent ; Child ; Aged ; Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19/epidemiology ; Reinfection ; Pandemics ; }, abstract = {We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge.}, } @article {pmid37628830, year = {2023}, author = {Sfera, A and Rahman, L and Zapata-Martín Del Campo, CM and Kozlakidis, Z}, title = {Long COVID as a Tauopathy: Of "Brain Fog" and "Fusogen Storms".}, journal = {International journal of molecular sciences}, volume = {24}, number = {16}, pages = {}, pmid = {37628830}, issn = {1422-0067}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; *Tauopathies ; Brain ; }, abstract = {Long COVID, also called post-acute sequelae of SARS-CoV-2, is characterized by a multitude of lingering symptoms, including impaired cognition, that can last for many months. This symptom, often called "brain fog", affects the life quality of numerous individuals, increasing medical complications as well as healthcare expenditures. The etiopathogenesis of SARS-CoV-2-induced cognitive deficit is unclear, but the most likely cause is chronic inflammation maintained by a viral remnant thriving in select body reservoirs. These viral sanctuaries are likely comprised of fused, senescent cells, including microglia and astrocytes, that the pathogen can convert into neurotoxic phenotypes. Moreover, as the enteric nervous system contains neurons and glia, the virus likely lingers in the gastrointestinal tract as well, accounting for the intestinal symptoms of long COVID. Fusogens are proteins that can overcome the repulsive forces between cell membranes, allowing the virus to coalesce with host cells and enter the cytoplasm. In the intracellular compartment, the pathogen hijacks the actin cytoskeleton, fusing host cells with each other and engendering pathological syncytia. Cell-cell fusion enables the virus to infect the healthy neighboring cells. We surmise that syncytia formation drives cognitive impairment by facilitating the "seeding" of hyperphosphorylated Tau, documented in COVID-19. In our previous work, we hypothesized that the SARS-CoV-2 virus induces premature endothelial senescence, increasing the permeability of the intestinal and blood-brain barrier. This enables the migration of gastrointestinal tract microbes and/or their components into the host circulation, eventually reaching the brain where they may induce cognitive dysfunction. For example, translocated lipopolysaccharides or microbial DNA can induce Tau hyperphosphorylation, likely accounting for memory problems. In this perspective article, we examine the pathogenetic mechanisms and potential biomarkers of long COVID, including microbial cell-free DNA, interleukin 22, and phosphorylated Tau, as well as the beneficial effect of transcutaneous vagal nerve stimulation.}, } @article {pmid37628505, year = {2023}, author = {López-López, L and Calvache-Mateo, A and Ortiz-Rubio, A and Granados-Santiago, M and Heredia-Ciuró, A and Martín-Núñez, J and Valenza, MC}, title = {Differences of Disabling Symptoms between Previously Hospitalized or Non-Hospitalized Currently Working Long-COVID Survivors One Year after Infection: A Descriptive Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {16}, pages = {}, pmid = {37628505}, issn = {2227-9032}, support = {19/02609//Ministerio de Educación y Formación Profesional/ ; 20/01670//Ministerio de Educación y Formación Profesional/ ; 21/00451//Ministerio de Educación y Formación Profesional/ ; 06195/21D/MA//College of Physiotherapists of Andalucia/ ; }, abstract = {This study aimed to describe the presence of disabling symptoms in currently working Long-COVID survivors by comparing the hospitalized and non-hospitalized one year after infection. Patients with Long-COVID syndrome (LCS) that have been infected by COVID-19 a year ago and were actually working were included. Participants that had been hospitalized due to COVID-19 were included in the LCS hospitalized group, and participants that had not been hospitalized were included in the LCS non-hospitalized group. The eligible patients were prompted to complete the latest self-report version of the COVID-19 Yorkshire Rehabilitation Screening Tool (C19-YRS). A total of 465 subjects were included in the study. Participants in the LCS hospitalized group were significantly older, had a significantly higher BMI, and had a significantly higher prevalence of women compared to the LCS non-hospitalized group. Additionally, participants in the LCS hospitalized group had obtained significantly worse results in symptom severity, functional disability, and global health perceived subscales of C19-YRS compared to the participants included in the LCS non-hospitalized group. We concluded that disabling symptoms are presented in patients with LCS at working age one year after infection and are higher in LCS hospitalized patients compared to LCS non-hospitalized patients.}, } @article {pmid37628475, year = {2023}, author = {Sick, J and König, D}, title = {Exercise Training in Non-Hospitalized Patients with Post-COVID-19 Syndrome-A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {16}, pages = {}, pmid = {37628475}, issn = {2227-9032}, abstract = {Post COVID-19 Syndrome (PCS) is the persistence of symptoms after an infection with SARS-CoV-2 in both hospitalized and non-hospitalized COVID-19 survivors. Exercise was proposed as a rehabilitation measure for PCS and early studies focused on patients post-hospital discharge. The objective of this review is to summarize the results of trials investigating exercise interventions in non-hospitalized subjects with PCS and propose practical recommendations concerning safe exercise programming. A literature search in the databases MEDLINE and Scopus was conducted until 26 July 2023 and resulted in seven studies that met the criteria. In total, 935 subjects with PCS were investigated. Exercise enhanced aerobic fitness and physical function and relieved symptoms of dyspnea, fatigue and depression. Participants reported lower Post COVID-19 Functional Status scores post-intervention. The exercise programs were well tolerated with no adverse events. To ensure safety, medical examinations should take place in advance and there should be a regular evaluation of the individual responses to the training. Caution is advised when working with patients suffering from post-exertional malaise or diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome. There is a growing need for additional randomized controlled trials to investigate the effectiveness and safety of exercise in individuals with PCS.}, } @article {pmid37626992, year = {2023}, author = {Shabani, Z and Liu, J and Su, H}, title = {Vascular Dysfunctions Contribute to the Long-Term Cognitive Deficits Following COVID-19.}, journal = {Biology}, volume = {12}, number = {8}, pages = {}, pmid = {37626992}, issn = {2079-7737}, support = {R01 HL122774/NH/NIH HHS/United States ; R01 NS027713/NS/NINDS NIH HHS/United States ; NS112819/NH/NIH HHS/United States ; IK6 BX004600/BX/BLRD VA/United States ; R01 HL122774/HL/NHLBI NIH HHS/United States ; I01 BX003335/BX/BLRD VA/United States ; NS027713/NH/NIH HHS/United States ; R01 NS102886/NS/NINDS NIH HHS/United States ; R01 NS112819/NS/NINDS NIH HHS/United States ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.}, } @article {pmid37626956, year = {2023}, author = {Ramamoorthy, R and Hussain, H and Ravelo, N and Sriramajayam, K and Di Gregorio, DM and Paulrasu, K and Chen, P and Young, K and Masciarella, AD and Jayakumar, AR and Paidas, MJ}, title = {Kidney Damage in Long COVID: Studies in Experimental Mice.}, journal = {Biology}, volume = {12}, number = {8}, pages = {}, pmid = {37626956}, issn = {2079-7737}, support = {0000//University of Miami Miller School of Medicine Department Obstetrics, Gynecology and Reproductive Sciences/ ; 0000//Muriel, Murray & Robert Smith Foundation COVID-19 Research Fund/ ; 0000//University of Miami Miller School of Medicine Team Science Award/ ; 0000//Charles M. Vallee Foundation/ ; }, abstract = {Signs and symptoms involving multiple organ systems which persist for weeks or months to years after the initial SARS-CoV-2 infection (also known as PASC or long COVID) are common complications of individuals with COVID-19. We recently reported pathophysiological changes in various organs post-acute infection of mice with mouse hepatitis virus-1 (MHV-1, a coronavirus) (7 days) and after long-term post-infection (12 months). One of the organs severely affected in this animal model is the kidney, which correlated well with human studies showing kidney injury post-SARS-CoV-2 infection. Our long-term post-infection pathological observation in kidneys includes the development of edema and inflammation of the renal parenchyma, severe acute tubular necrosis, and infiltration of macrophages and lymphocytes, in addition to changes observed in both acute and long-term post-infection, which include tubular epithelial cell degenerative changes, peritubular vessel congestion, proximal and distal tubular necrosis, hemorrhage in the interstitial tissue, and vacuolation of renal tubules. These findings strongly suggest the possible development of renal fibrosis, in particular in the long-term post-infection. Accordingly, we investigated whether the signaling system that is known to initiate the above-mentioned changes in kidneys in other conditions is also activated in long-term post-MHV-1 infection. We found increased TGF-β1, FGF23, NGAL, IL-18, HIF1-α, TLR2, YKL-40, and B2M mRNA levels in long-term post-MHV-1 infection, but not EGFR, TNFR1, BCL3, and WFDC2. However, only neutrophil gelatinase-associated lipocalin (NGAL) increased in acute infection (7 days). Immunoblot studies showed an elevation in protein levels of HIF1-α, TLR-2, and EGFR in long-term post-MHV-1 infection, while KIM-1 and MMP-7 protein levels are increased in acute infection. Treatment with a synthetic peptide, SPIKENET (SPK), which inhibits spike protein binding, reduced NGAL mRNA in acute infection, and decreased TGF-β1, BCL3 mRNA, EGFR, HIF1-α, and TLR-2 protein levels long-term post-MHV-1 infection. These findings suggest that fibrotic events may initiate early in SARS-CoV-2 infection, leading to pronounced kidney fibrosis in long COVID. Targeting these factors therapeutically may prevent acute or long-COVID-associated kidney complications.}, } @article {pmid37626917, year = {2023}, author = {Sriramula, S and Theobald, D and Parekh, RU and Akula, SM and O'Rourke, DP and Eells, JB}, title = {Emerging Role of Kinin B1 Receptor in Persistent Neuroinflammation and Neuropsychiatric Symptoms in Mice Following Recovery from SARS-CoV-2 Infection.}, journal = {Cells}, volume = {12}, number = {16}, pages = {}, pmid = {37626917}, issn = {2073-4409}, support = {R01 HL153115/HL/NHLBI NIH HHS/United States ; R21 NR010361/NR/NINR NIH HHS/United States ; }, mesh = {Female ; Male ; Animals ; Humans ; Mice ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Neuroinflammatory Diseases ; Kinins ; }, abstract = {Evidence suggests that patients with long COVID can experience neuropsychiatric, neurologic, and cognitive symptoms. However, these clinical data are mostly associational studies complicated by confounding variables, thus the mechanisms responsible for persistent symptoms are unknown. Here we establish an animal model of long-lasting effects on the brain by eliciting mild disease in K18-hACE2 mice. Male and female K18-hACE2 mice were infected with 4 × 10[3] TCID50 of SARS-CoV-2 and, following recovery from acute infection, were tested in the open field, zero maze, and Y maze, starting 30 days post infection. Following recovery from SARS-CoV-2 infection, K18-hACE2 mice showed the characteristic lung fibrosis associated with SARS-CoV-2 infection, which correlates with increased expression of the pro-inflammatory kinin B1 receptor (B1R). These mice also had elevated expression of B1R and inflammatory markers in the brain and exhibited behavioral alterations such as elevated anxiety and attenuated exploratory behavior. Our data demonstrate that K18-hACE2 mice exhibit persistent effects of SARS-CoV-2 infection on brain tissue, revealing the potential for using this model of high sensitivity to SARS-CoV-2 to investigate mechanisms contributing to long COVID symptoms in at-risk populations. These results further suggest that elevated B1R expression may drive the long-lasting inflammatory response associated with SARS-CoV-2 infection.}, } @article {pmid37626797, year = {2023}, author = {Alijotas-Reig, J and Anunciación-Llunell, A and Morales-Pérez, S and Trapé, J and Esteve-Valverde, E and Miro-Mur, F}, title = {Thrombosis and Hyperinflammation in COVID-19 Acute Phase Are Related to Anti-Phosphatidylserine and Anti-Phosphatidylinositol Antibody Positivity.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626797}, issn = {2227-9059}, support = {SB-JAR-23//Synlab Group (Barcelona, Spain)/ ; Gravida-JAR-23//Catedra UAB-Gravida Medicina i Immunologia Reproductiva (Barcelona, Spain)/ ; SEMCC-JAR-22//Sociedad Española de Medicina y Cirugía Cosmética (SEMCC)/ ; }, abstract = {Antiphospholipid antibodies (APLA) are strongly associated with thrombosis seen in patients with antiphospholipid syndrome. In COVID-19, thrombosis has been observed as one of the main comorbidities. In patients hospitalised for COVID-19, we want to check whether APLA positivity is associated with COVID-19-related thrombosis, inflammation, severity of disease, or long COVID-19. We enrolled 92 hospitalised patients with COVID-19 between March and April 2020 who were tested for 18 different APLAs (IgG and IgM) with a single line-immunoassay test. A total of 30 healthy blood donors were used to set the cut-off for each APLA positivity. Of the 92 COVID-19 inpatients, 30 (32.61%; 95% CI [23.41-43.29]) tested positive for APLA, of whom 10 (33.3%; 95% CI [17.94-52.86]) had more than one APLA positivity. Anti-phosphatidylserine IgM positivity was described in 5.4% of inpatients (n = 5) and was associated with the occurrence of COVID-19-related thrombosis (p = 0.046). Anti-cardiolipin IgM positivity was the most prevalent among the inpatients (n = 12, 13.0%) and was associated with a recorded thrombosis in their clinical history (p = 0.044); however, its positivity was not associated with the occurrence of thrombosis during their hospitalisation for COVID-19. Anti-phosphatidylinositol IgM positivity, with a prevalence of 5.4% (n = 5), was associated with higher levels of interleukin (IL)-6 (p = 0.007) and ferritin (p = 0.034). Neither of these APLA positivities was a risk factor for COVID-19 severity or a predictive marker for long COVID-19. In conclusion, almost a third of COVID-19 inpatients tested positive for at least one APLA. Anti-phosphatidylserine positivity in IgM class was associated with thrombosis, and anti-phosphatidylinositol positivity in IgM class was associated with inflammation, as noticed by elevated levels of IL-6. Thus, testing for non-criteria APLA to assess the risk of clinical complications in hospitalised COVID-19 patients might be beneficial. However, they were not related to disease severity or long COVID-19.}, } @article {pmid37626764, year = {2023}, author = {Kaszuba, M and Madej, N and Pilinski, R and Sliwka, A}, title = {Post-COVID-19 Symptoms in Adults with Asthma-Systematic Review.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626764}, issn = {2227-9059}, abstract = {BACKGROUND: Research on the longer-term sequelae of COVID-19 in patients with asthma is limited.

OBJECTIVE: To assess the frequency and severity of long-term symptoms of COVID-19 in the population of asthma patients.

METHODS: A systematic review of the published literature was conducted in accordance with the recommendations of the PRISMA statement. EMBASE, MEDLINE/PubMed, Web of Science, CINAHL, and Scopus Scholar were searched for terms related to asthma and post or long COVID-19, and for systematic reviews related to specific questions within our review, up to June 2022.

RESULTS: Data from 9 references publications included in the review were extracted. A total of 1466 adult asthmatic patients with COVID-19 infection were described in all the publications mentioned above. Of the long-term symptoms reported after COVID-19, patients indicated: lower respiratory symptoms, fatigue, cognitive symptoms, psychological problems, and other such as skin rashes, gastrointestinal disorders, tachycardia, palpitations, ocular disorders, ageusia/hypogeusia, anosmia/hyposmia, and poor sleep quality. These symptoms in similar intensity were observed in the comparison groups without a diagnosis of asthma.

CONCLUSIONS: The published data neither confirm nor deny that long-term COVID-19 symptoms in patients with asthma diagnosis are different in strength and frequency from patients without asthma diagnosis. To indicate associations between asthma and COVID-19 infection and severity, as well as the frequency of long-term symptoms of COVID-19, more longitudinal research is needed in chronic asthma patients with different phenotypes, intensity of treatment, and degree of asthma control.}, } @article {pmid37626735, year = {2023}, author = {Santoro, L and Zaccone, V and Falsetti, L and Ruggieri, V and Danese, M and Miro, C and Di Giorgio, A and Nesci, A and D'Alessandro, A and Moroncini, G and Santoliquido, A}, title = {Role of Endothelium in Cardiovascular Sequelae of Long COVID.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626735}, issn = {2227-9059}, abstract = {The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although SARS-CoV-2 primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. The virus is able to penetrate the endothelial barrier, damaging it directly or indirectly and causing endotheliitis and multi-organ injury. Several mechanisms cooperate to development of endothelial dysfunction, including endothelial cell injury and pyroptosis, hyperinflammation and cytokine storm syndrome, oxidative stress and reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, and thrombosis. After acute-phase infection, some patients reported signs and symptoms of a systemic disorder known as long COVID, in which a broad range of cardiovascular (CV) disorders emerged. To date, the exact pathophysiology of long COVID remains unclear: in addition to the persistence of acute-phase infection mechanisms, specific pathways of CV damage have been postulated, such as persistent viral reservoirs in the heart or an autoimmune response to cardiac antigens through molecular mimicry. The aim of this review is to provide an overview of the main molecular patterns of enduring endothelial activation following SARS-CoV-2 infection and to offer the latest summary of CV complications in long COVID.}, } @article {pmid37626710, year = {2023}, author = {Meléndez-Oliva, E and Martínez-Pozas, O and Cuenca-Zaldívar, JN and Villafañe, JH and Jiménez-Ortega, L and Sánchez-Romero, EA}, title = {Efficacy of Pulmonary Rehabilitation in Post-COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626710}, issn = {2227-9059}, abstract = {BACKGROUND: This systematic review and meta-analysis examines how pulmonary rehabilitation impacts in patients suffering from subacute and long COVID-19 infections, gauging enhancements in of dyspnea, physical function, quality of life, psychological state (anxiety and depression), and fatigue.

METHODS: Three electronic databases (PubMed, Web of Science, Cochrane Library) were systematically searched for full-text articles published from inception to January 2023. Randomized, quasi-experimental, and observational studies were included, with adults diagnosed with subacute or long COVID-19 who received pulmonary rehabilitation as intervention. Outcomes related to dyspnea, physical function, quality of life, fatigue, and psychological status were included. Risk of bias was assessed with Cochrane Risk of Bias Tool for Randomized Controlled Trials and Risk of bias in non-randomized studies of intervention. The review was registered before starting in PROSPERO (CRD: 42022373075).

RESULTS: Thirty-four studies were included, involving 1970 patients with subacute and long COVID-19. The meta-analysis demonstrated moderate to large effects on dyspnea, physical function, quality of life, and depressive symptoms compared to usual care intervention. No significant differences were found in fatigue compared to usual care, nor in anxiety levels after pulmonary rehabilitation intervention.

CONCLUSIONS: Pulmonary rehabilitation has the potential to improve health outcomes in patients with subacute and long COVID-19. However, due to the high risk of bias of included studies, conclusions should be taken with caution.}, } @article {pmid37626615, year = {2023}, author = {Ghimire, B and Pour, SK and Middleton, E and Campbell, RA and Nies, MA and Aghazadeh-Habashi, A}, title = {Renin-Angiotensin System Components and Arachidonic Acid Metabolites as Biomarkers of COVID-19.}, journal = {Biomedicines}, volume = {11}, number = {8}, pages = {}, pmid = {37626615}, issn = {2227-9059}, support = {K01 AG059892/AG/NIA NIH HHS/United States ; Office for Research Internal Small Grant Program//Idaho State University/ ; }, abstract = {Through the ACE2, a main enzyme of the renin-angiotensin system (RAS), SARS-CoV-2 gains access into the cell, resulting in different complications which may extend beyond the RAS and impact the Arachidonic Acid (ArA) pathway. The contribution of the RAS through ArA pathways metabolites in the pathogenesis of COVID-19 is unknown. We investigated whether RAS components and ArA metabolites can be considered biomarkers of COVID-19. We measured the plasma levels of RAS and ArA metabolites using an LC-MS/MS. Results indicate that Ang 1-7 levels were significantly lower, whereas Ang II levels were higher in the COVID-19 patients than in healthy control individuals. The ratio of Ang 1-7/Ang II as an indicator of the RAS classical and protective arms balance was dramatically lower in COVID-19 patients. There was no significant increase in inflammatory 19-HETE and 20-HETE levels. The concentration of EETs was significantly increased in COVID-19 patients, whereas the DHETs concentration was repressed. Their plasma levels were correlated with Ang II concentration in COVID-19 patients. In conclusion, evaluating the RAS and ArA pathway biomarkers could provide helpful information for the early detection of high-risk groups, avoid delayed medical attention, facilitate resource allocation, and improve patient clinical outcomes to prevent long COVID incidence.}, } @article {pmid37623461, year = {2023}, author = {Menotti, S and Giampietro, A and Raia, S and Veleno, M and Angelini, F and Tartaglione, T and Gaudino, S and Doglietto, F and De Marinis, L and Pontecorvi, A and Bianchi, A and Chiloiro, S}, title = {Unveiling the Etiopathogenic Spectrum of Hypophysitis: A Narrative Review.}, journal = {Journal of personalized medicine}, volume = {13}, number = {8}, pages = {}, pmid = {37623461}, issn = {2075-4426}, abstract = {Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes. The chronic phase is characterized by progressive and irreversible pituitary atrophy. APA may play a role in the management, diagnosis, and prognosis of PAH. Specific autoantibodies such as anti-GH, anti-PIT-1, and anti-T-PIT have been found in patients with hypophysitis and hypopituitarism. A recent study suggested that a mechanism of escaping clonal deletion and mounting an immune response against self antigens can explain the unusual nature of the immune response observed in PAH patients. A cytokine array shows the presence of gamma-interferon and interleukin-17. Patients carrying mutations in the PIT1 or PROP1 genes may present PAH. Individuals carrying the HLA DQ8 haplotype are four times more likely to develop PAH. Immune checkpoint inhibitors induce hypophysitis (IIHs): IIHs is an increasingly frequent toxicity of in patients on treatment with inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). ICIs inhibit the CTLA-4 pathway, leading to overactivation of T lymphocytes. The binding of PD-1/PD-L1 suppresses the activity of T cells, promotes the conversion of T-helpers into T-regulatory cells, and activates pro-survival signaling pathways in cancer cells. Cytokines play a crucial role in IIHs. B-cell infiltration has been observed in IIHs, suggesting that antibody-mediated pituitary injury may contribute. Genetic polymorphisms of CTLA-4 and PD-1 genes can increase the risk of IIHs. HLA alleles may also be involved in the onset of IIHs; this HLA association presents a possible alternative mechanistic hypothesis. IIHs may also be linked to a paraneoplastic syndrome triggered by ectopic expression of pituitary specific antigens. SARS-CoV-2-related hypophysitis: Recently, the literature has reported occurrences of hypophysitis associated with the SARS-CoV-2 virus; long COVID-19 may also present as infundibulo-neuro-hypophysitis. The virus enters the central nervous system because of its distinct interaction with angiotensin-converting enzyme receptors via spike proteins binding the capillary endothelium, and it directly damages the pituitary cells. The effect of SARS-CoV-2 can occur indirectly through inflammation and the release of cytokines. The exact mechanism remains ambiguous. The available data on endocrine complications associated with the SARS-CoV-2 vaccine are scant. Nonetheless, isolated cases of hypophysitis have been documented. Treatment of hypophysitis: Glucocorticoids are the cornerstone in managing primary hypophysitis, given their targeted action on inflammation. A better understanding of the etiopathogenesis and molecular mechanism of hypophysitis can lead to more effective and personalized treatment strategies.}, } @article {pmid37623441, year = {2023}, author = {Suppini, N and Fira-Mladinescu, O and Traila, D and Motofelea, AC and Marc, MS and Manolescu, D and Vastag, E and Maganti, RK and Oancea, C}, title = {Longitudinal Analysis of Pulmonary Function Impairment One Year Post-COVID-19: A Single-Center Study.}, journal = {Journal of personalized medicine}, volume = {13}, number = {8}, pages = {}, pmid = {37623441}, issn = {2075-4426}, abstract = {Persistent pulmonary impairment post-COVID-19 has been reported, albeit variably. This single-center observational study aims to longitudinally evaluate pulmonary function in 140 COVID-19 survivors one year after recovery, assessing associations with disease severity and pre-existing lung conditions. Participants aged 18 and older, with confirmed SARS-CoV-2 infection, were evaluated using spirometry and Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) tests. Pulmonary function parameters like Forced Expiratory Volume at 1 s (FEV1), Forced Vital Capacity (FVC), and Total Lung Capacity (TLC) were measured. Participants were stratified by age, gender, body mass index, smoking status, and lung damage severity via computed tomography (CT). The cohort consisted of mostly males (58.6%), with a mean age of 53.8 years and body mass index of 24.9 kg/m[2]. Post-COVID fibrosis was seen in 22.7%, 27.3%, and 51.9% of mild, moderate, and severe disease patients, respectively (p = 0.003). FVC significantly reduced with disease severity (p < 0.001), while FEV1, FEF25-75, and DLCO showed a non-significant downward trend. FEV1/FVC ratio increased with disease severity (p = 0.033), and TLC and RV significantly declined (p = 0.023 and p = 0.003, respectively). A one-year follow-up indicated a non-significant change in FVC, FEV1, FEV1/FVC ratio, FEF25-75, and RV compared with the 40-day measurement, but it revealed significant improvements in DLCO and TLC (p = 0.010). There were significant mean increases in FVC, FEV1, DLCO, TLC, and RV across all disease severities over one year. They were most pronounced in the patients with a history of severe COVID-19, who had a better recovery over one year, compared with the mild and moderate COVID-19 patients whose lung function almost normalized. One year after the SARS-CoV-2 infection, we observed a significant association between disease severity and post-COVID fibrotic changes. Though some lung function parameters remained stable over the year, significant improvements were noted in DLCO and TLC. Particularly, individuals with severe disease showed substantial recovery in lung function, indicating the potential reversibility of COVID-19-related pulmonary damage.}, } @article {pmid37621592, year = {2023}, author = {Elbeltagi, R and Al-Beltagi, M and Saeed, NK and Bediwy, AS}, title = {COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review.}, journal = {World journal of clinical cases}, volume = {11}, number = {22}, pages = {5252-5272}, pmid = {37621592}, issn = {2307-8960}, abstract = {BACKGROUND: It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial symptom. The severity of coronavirus disease 2019 (COVID-19) is often reflected in the prevalence of gastrointestinal symptoms. COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction. There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.

AIM: To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction, including its manifestations, potential mechanisms, diagnosis, differential diagnosis, impact on quality of life, prognosis, and management and prevention strategies.

METHODS: We conducted a thorough systematic search across various databases and performed an extensive literature review. Our review encompassed 113 studies published in English from January 2000 to April 18, 2023.

RESULTS: According to most of the literature, gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis. Numerous factors can influence gastrointestinal autonomic nervous functions. Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues, and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways. These symptoms include anorexia, dysgeusia, heartburn, belching, chest pain, regurgitation, vomiting, epigastric burn, diarrhea, abdominal pain, bloating, irregular bowel movements, and constipation. Diarrhea is the most prevalent symptom, followed by anorexia, nausea, vomiting, and abdominal pain. Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms, COVID-19-induced autonomic effects significantly impact the patient's condition, general health, prognosis, and quality of life. Early diagnosis and proper recognition are crucial for improving outcomes. It is important to consider the differential diagnosis, as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction. Treating this dysfunction can be a challenging task.

CONCLUSION: To ensure the best possible outcomes for COVID-19 patients, it is essential to take a multidisciplinary approach involving providing supportive care, treating the underlying infection, managing dysfunction, monitoring for complications, and offering nutritional support. Close monitoring of the patient's condition is crucial, and prompt intervention should be taken if necessary. Furthermore, conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.}, } @article {pmid37620042, year = {2023}, author = {Taylor, SJC and Sohanpal, R and Steed, L and Marshall, K and Chan, C and Yaziji, N and Barradell, AC and Font-Gilabert, P and Healey, A and Hooper, R and Kelly, MJ and Mammoliti, KM and Priebe, S and Rajasekaran, A and Roberts, CM and Rowland, V and Singh, SJ and Smuk, M and Underwood, M and Waseem, S and White, P and Wileman, V and Pinnock, H}, title = {Tailored psychological intervention for anxiety or depression in COPD (TANDEM): a randomised controlled trial.}, journal = {The European respiratory journal}, volume = {62}, number = {5}, pages = {}, pmid = {37620042}, issn = {1399-3003}, support = {/WT_/Wellcome Trust/United Kingdom ; 13/146/02/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *Depression/therapy ; Psychosocial Intervention ; Anxiety/therapy ; Anxiety Disorders ; *Pulmonary Disease, Chronic Obstructive/complications/therapy ; Quality of Life ; }, abstract = {BACKGROUND: The TANDEM multicentre, pragmatic, randomised controlled trial evaluated whether a tailored psychological intervention based on a cognitive behavioural approach for people with COPD and symptoms of anxiety and/or depression improved anxiety or depression compared with usual care (control).

METHODS: People with COPD and moderate to very severe airways obstruction and Hospital Anxiety and Depression Scale subscale scores indicating mild to moderate anxiety (HADS-A) and/or depression (HADS-D) were randomised 1.25:1 (242 intervention and 181 control). Respiratory health professionals delivered the intervention face-to-face over 6-8 weeks. Co-primary outcomes were HADS-A and HADS-D measured 6 months post-randomisation. Secondary outcomes at 6 and 12 months included: HADS-A and HADS-D (12 months), Beck Depression Inventory II, Beck Anxiety Inventory, St George's Respiratory Questionnaire, social engagement, the EuroQol instrument five-level version (EQ-5D-5L), smoking status, completion of pulmonary rehabilitation, and health and social care resource use.

RESULTS: The intervention did not improve anxiety (HADS-A mean difference -0.60, 95% CI -1.40-0.21) or depression (HADS-D mean difference -0.66, 95% CI -1.39-0.07) at 6 months. The intervention did not improve any secondary outcomes at either time-point, nor did it influence completion of pulmonary rehabilitation or healthcare resource use. Deaths in the intervention arm (13/242; 5%) exceeded those in the control arm (3/181; 2%), but none were associated with the intervention. Health economic analysis found the intervention highly unlikely to be cost-effective.

CONCLUSION: This trial has shown, beyond reasonable doubt, that this cognitive behavioural intervention delivered by trained and supervised respiratory health professionals does not improve psychological comorbidity in people with advanced COPD and depression or anxiety.}, } @article {pmid37615735, year = {2024}, author = {Caamano, E and Velasco, L and Garcia, MV and Asencio, JM and Piñeiro, P and Hortal, J and Garutti, I}, title = {Prognostic factors for deterioration of quality of life one year after admission to ICU for severe SARS-COV2 infection.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {33}, number = {1}, pages = {123-132}, pmid = {37615735}, issn = {1573-2649}, mesh = {Humans ; Female ; Male ; *Quality of Life/psychology ; RNA, Viral ; Prognosis ; *COVID-19/epidemiology ; SARS-CoV-2 ; Intensive Care Units ; }, abstract = {PURPOSE: Patients with COVID-19 present long-term symptoms collectively known as "post-COVID syndrome". Long-term manifestations are more frequent in patients requiring admission to Intensive Care Units (ICU), but the risk factors for their development are still unknown. This study explores the quality of life of patients with severe COVID-19 one year after their discharge from ICU.

METHODS: Prospective observational study including 106 patients admitted to the ICU of a tertiary care hospital between March and August 2020. We analysed quality of life using the EuroQol-5D index (EQ-5D). We evaluated as possible risk factors associated with a worse value of the EQ-5D index the medical record, the clinical situation at hospital admission, the clinical situation at ICU admission and evolution in the ICU. As a secondary objective, we explored the presence of other frequent symptoms.

RESULTS: Most patients (55.4%) reported that their quality of life worsened one year after admission. The mean perceived health status, on the EQ-VAS scale (0-100), was 70.4, with a median of 70 (RI 60-90). The median EQ-5D index was 0.91 (RI 0.76-1). The factors independently related to lower quality of life were female sex and duration of mechanical ventilation. Almost all (91%) of the patients had sequelae one year after discharge from the ICU. The most frequent manifestations were neuropsychiatric (71%).

CONCLUSIONS: Critically ill COVID-19 patients worsen their quality of life more than one year after discharge. Female sex and duration of mechanical ventilation predict a lower quality of life assessed by the EQ-5D index.}, } @article {pmid37612439, year = {2023}, author = {Moatar, AI and Chis, AR and Romanescu, M and Ciordas, PD and Nitusca, D and Marian, C and Oancea, C and Sirbu, IO}, title = {Plasma miR-195-5p predicts the severity of Covid-19 in hospitalized patients.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13806}, pmid = {37612439}, issn = {2045-2322}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *MicroRNAs/genetics ; Patients ; *Fatigue Syndrome, Chronic ; }, abstract = {Predicting the clinical course of Covid-19 is a challenging task, given the multi-systemic character of the disease and the paucity of minimally invasive biomarkers of disease severity. Here, we evaluated the early (first two days post-admission) level of circulating hsa-miR-195-5p (miR-195, a known responder to viral infections and SARS-CoV-2 interactor) in Covid-19 patients and assessed its potential as a biomarker of disease severity. We show that plasma miR-195 correlates with several clinical and paraclinical parameters, and is an excellent discriminator between the severe and mild forms of the disease. Our Gene Ontology analysis of miR-195 targets differentially expressed in Covid-19 indicates a strong impact on cardiac mitochondria homeostasis, suggesting a possible role in long Covid and chronic fatigue syndrome (CFS) syndromes.}, } @article {pmid37612310, year = {2023}, author = {Altmann, DM and Reynolds, CJ and Joy, G and Otter, AD and Gibbons, JM and Pade, C and Swadling, L and Maini, MK and Brooks, T and Semper, A and McKnight, Á and Noursadeghi, M and Manisty, C and Treibel, TA and Moon, JC and , and Boyton, RJ}, title = {Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {5139}, pmid = {37612310}, issn = {2041-1723}, support = {/BHF_/British Heart Foundation/United Kingdom ; MR/S019553/1/MRC_/Medical Research Council/United Kingdom ; MR/R02622X/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Antibodies, Viral ; Asymptomatic Infections ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; T-Lymphocytes ; }, abstract = {Among the unknowns in decoding the pathogenesis of SARS-CoV-2 persistent symptoms in Long Covid is whether there is a contributory role of abnormal immunity during acute infection. It has been proposed that Long Covid is a consequence of either an excessive or inadequate initial immune response. Here, we analyze SARS-CoV-2 humoral and cellular immunity in 86 healthcare workers with laboratory confirmed mild or asymptomatic SARS-CoV-2 infection during the first wave. Symptom questionnaires allow stratification into those with persistent symptoms and those without for comparison. During the period up to 18-weeks post-infection, we observe no difference in antibody responses to spike RBD or nucleoprotein, virus neutralization, or T cell responses. Also, there is no difference in the profile of antibody waning. Analysis at 1-year, after two vaccine doses, comparing those with persistent symptoms to those without, again shows similar SARS-CoV-2 immunity. Thus, quantitative differences in these measured parameters of SARS-CoV-2 adaptive immunity following mild or asymptomatic acute infection are unlikely to have contributed to Long Covid causality. ClinicalTrials.gov (NCT04318314).}, } @article {pmid37610793, year = {2023}, author = {Harris, E}, title = {Two New Analyses Add to Long COVID Understanding.}, journal = {JAMA}, volume = {330}, number = {10}, pages = {905-906}, doi = {10.1001/jama.2023.15449}, pmid = {37610793}, issn = {1538-3598}, mesh = {Humans ; COVID-19 ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; United States/epidemiology ; }, } @article {pmid37606967, year = {2023}, author = {Cui, S and Xiong, H and Feng, Z and Chu, Y and Que, C and Qin, J and Pan, Y and Yu, K and Jia, L and Yao, X and Liao, J and Huo, D and Guo, C and Zhao, H and Xu, M and Tian, Y and Peng, Q and Li, F and Xu, H and Hong, R and Zhang, D and Wang, G and Yang, P and Gao, GF and Wang, Q}, title = {Severe pigeon paramyxovirus 1 infection in a human case with probable post-COVID-19 condition.}, journal = {Emerging microbes & infections}, volume = {12}, number = {2}, pages = {2251600}, pmid = {37606967}, issn = {2222-1751}, mesh = {Male ; Animals ; Humans ; Aged ; *COVID-19 ; Columbidae ; Newcastle disease virus/genetics ; Post-Acute COVID-19 Syndrome ; Antigenic Variation ; }, abstract = {Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient's sputum and in cloacal smear samples from domesticated pigeons belonging to the patient's neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.}, } @article {pmid37606649, year = {2024}, author = {Tsai, J and Grace, A and Espinoza, R and Kurian, A}, title = {Incidence of long COVID and associated psychosocial characteristics in a large U.S. city.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {59}, number = {4}, pages = {611-619}, pmid = {37606649}, issn = {1433-9285}, mesh = {Adult ; Humans ; Female ; Male ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Incidence ; Surveys and Questionnaires ; }, abstract = {PURPOSE: Persistent residual effects from Coronavirus Disease-2019 (COVID-19) have been observed with varying definitions of "Long COVID" and little comprehensive examination. This study examined the incidence and psychosocial correlates of Long COVID using different definitions.

METHODS: Data were analyzed from a citywide sample of 3595 adults with lab-confirmed cases of COVID-19 that were surveyed over 3 months. Rates of Long COVID were examined in terms of Post-Acute COVID (PAC), defined as at least one symptom lasting for 4 weeks, and three levels of Post-COVID Syndrome (PCS) that included experiencing at least one symptom for 3 months (PCS-1), experiencing three or more symptoms for 3 months (PCS-2), or experiencing at least one of the same symptoms for 3 months (PCS-3).

RESULTS: Among the 686 participants who completed baseline, 1-month, and 3-month follow-up assessments, 75.7% had PAC, 55.0% had PSC-1, 26.5% had PSC-2, and 19.0% had PSC-3. Comparing participants with PAC and PSC-3 in the total sample with inverse probability weighting, multivariable analyses revealed being female, Asian or Native American, greater reported longlines, and less social support were predictive of PCS-3.

CONCLUSION: Residual effects of COVID-19 are very common and nearly one-fifth of our sample met the most restrictive definition of Long COVID warranting concern as a public health issue. Some demographic and social factors may predispose some adults to Long COVID, which should be considered for prevention and population health.}, } @article {pmid37606391, year = {2023}, author = {Rossi, S and Prodi, E and Morese, R and Paone, G and Ruberto, T and Sacco, L}, title = {Persistent 18F-FDG Brain PET Fronto-Temporal Hypometabolism and Cognitive Symptoms Two Years after SARS-CoV-2 Infection: A Case Report.}, journal = {Neurology international}, volume = {15}, number = {3}, pages = {908-916}, pmid = {37606391}, issn = {2035-8385}, abstract = {At least 10% of patients experience persistent symptoms after SARS-CoV-2 infection, a condition referred to as post-acute COVID-19, post-acute sequelae of SARS-CoV-2 infection (PASC), long COVID, long-haul COVID, long-term effects of COVID, post-COVID-19 and chronic COVID. In this report, we describe a case of persistent cognitive deficits developed after SARS-CoV-2 infection in a 40-year-old woman with a family history of early-onset Alzheimer's disease (EOAD) since her father was diagnosed with EOAD at the age of 50. We describe the clinical picture and workup, with special emphasis on the alterations of brain glucose metabolism evidenced by 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET), which could be considered a useful marker of the presence and persistence of cognitive deficits.}, } @article {pmid37606034, year = {2023}, author = {Li, X and Zhang, C and Bao, Z}, title = {Mast cell activation may contribute to adverse health transitions in COVID-19 patients with frailty.}, journal = {Emerging microbes & infections}, volume = {12}, number = {2}, pages = {2251589}, pmid = {37606034}, issn = {2222-1751}, mesh = {Humans ; Middle Aged ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Frailty ; Health Transition ; Mast Cells ; }, abstract = {A prominent aspect of the post-coronavirus disease-2019 (post-COVID-19) era is long-COVID. Therefore, precise patient classification and exploration of the corresponding factors affecting long-COVID are crucial for tailored treatment strategies. Frailty is a common age-related clinical syndrome characterized by deteriorated physiological functions of multiple organ systems, which increases susceptibility to stressors. Herein, we performed an inclusion and exclusion analysis (definite COVID-19 infection diagnosis, clear underlying disease information, ≥60 years old, and repeated sampling of clinical cases) of 10,613 blood samples and identified frailty cases for further investigation. RNA-Seq data were used for differential gene expression and functional and pathway analyses. The results revealed that patients with frailty were more prone to poor health conversions and more sequelae, and the blood transcriptome had obvious disturbances in pathways associated with immune regulation, metabolism, and stress response. These adverse health transitions were significantly associated with mast cell activation. Additionally, NCAPG, MCM10, and CDC25C were identified as hub genes in the peripheral blood differential gene cluster, which could be used as diagnostic markers of poor health conversion. Our results indicate that healthcare measures should be prioritized to mitigate adverse health outcomes in this vulnerable patient group, COVID-19 patients with frailty, in post-COVID era.}, } @article {pmid37605390, year = {2024}, author = {Hon, KLE and Leung, AKC and Tan, YW and Leung, KKY and Chan, PKS}, title = {SARS-CoV-2 Encephalitis versus Influenza Encephalitis: More Similarities than Differences.}, journal = {Current pediatric reviews}, volume = {20}, number = {4}, pages = {525-531}, pmid = {37605390}, issn = {1875-6336}, mesh = {Humans ; *Influenza, Human/complications/diagnosis/drug therapy ; *COVID-19/complications/diagnosis ; *Encephalitis, Viral/drug therapy/diagnosis ; *SARS-CoV-2 ; Child ; Antiviral Agents/therapeutic use ; }, abstract = {BACKGROUND: From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis.

OBJECTIVES: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis.

METHODS: A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis.

RESULTS: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease.

CONCLUSION: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.}, } @article {pmid37605232, year = {2023}, author = {Heidemann, C and Sarganas, G and Du, Y and Gaertner, B and Poethko-Müller, C and Cohrdes, C and Schmidt, S and Schlaud, M and Scheidt-Nave, C}, title = {Long-term health consequences among individuals with SARS-CoV-2 infection compared to individuals without infection: results of the population-based cohort study CoMoLo Follow-up.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1587}, pmid = {37605232}, issn = {1471-2458}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Cohort Studies ; Follow-Up Studies ; Pandemics ; Quality of Life ; SARS-CoV-2 ; Fatigue ; }, abstract = {BACKGROUND: Most of the previous studies on health sequelae of COVID-19 are uncontrolled cohorts and include a relatively short follow-up. This population-based multi-center cohort study examined health consequences among individuals about 1 to 1.5 years after SARS-CoV-2 infection compared with non-infected.

METHODS: The study population consisted of adults (≥ 18 years) from four municipalities particularly affected by the COVID-19 pandemic in the year 2020 who completed a detailed follow-up questionnaire on health-related topics. Exposure was the SARS-CoV-2 infection status (based on IgG antibodies, PCR test, or physician-diagnosis of COVID-19) at baseline (May to December 2020). Outcomes assessed at follow-up (October 2021 to January 2022; mean: 452 days) included recurrent or persistent health complaints, incident diseases, health-related quality of life (PROMIS-29), subjective health, and subjective memory impairment. Logistic and linear regression models were adjusted for baseline sociodemographic and lifestyle characteristics (age, sex, municipality, education, smoking, body mass index), pre-existing health conditions (chronic disease/health problem, health-related activity limitation, depressive/anxiety disorder), and follow-up time.

RESULTS: Among 4817 participants, 350 had a SARS-CoV-2 infection at baseline and 4467 had no infection at baseline or during follow-up. Those with an infection statistically significantly more often reported 7 out of 18 recurrent or persistent health complaints at follow-up: smell/taste disorders (12.8% vs. 3.4%, OR 4.11), shortness of breath (23.0% vs. 9.5%, 3.46), pain when breathing (4.7% vs. 1.9%, 2.36), fatigue (36.9% vs. 26.1%, 1.76), weakness in legs (12.8% vs. 7.8%, 1.93), myalgia/joint pain (21.9% vs. 15.1%, 1.53) and cough (30.8% vs. 24.8%, 1.34) and 3 out of 6 groups of incident diseases: liver/kidney (2.7% vs. 0.9%, 3.70), lung (3.2% vs. 1.1%, 3.50) and cardiovascular/metabolic (6.5% vs. 4.0%, 1.68) diseases. Those with an infection were significantly more likely to report poor subjective health (19.3% vs. 13.0%, 1.91), memory impairment (25.7% vs. 14.3%, 2.27), and worse mean scores on fatigue and physical function domains of PROMIS-29 than non-infected.

CONCLUSION: Even after more than one year, individuals with SARS-CoV-2 infection showed an increased risk of various health complaints, functional limitations, and worse subjective well-being, pointing toward profound health consequences of SARS-CoV-2 infection relevant for public health.}, } @article {pmid37604249, year = {2024}, author = {Ximeno-Rodríguez, I and Blanco-delRío, I and Astigarraga, E and Barreda-Gómez, G}, title = {Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes.}, journal = {Biomedical journal}, volume = {47}, number = {3}, pages = {100650}, pmid = {37604249}, issn = {2320-2890}, mesh = {Humans ; *SARS-CoV-2/genetics ; *Genotype ; *COVID-19/genetics/immunology/virology ; Acquired Immunodeficiency Syndrome/immunology/genetics ; Coronavirus Nucleocapsid Proteins/genetics/immunology ; Molecular Docking Simulation ; Lymphocytes/immunology/virology ; Phosphoproteins ; }, abstract = {BACKGROUND: Epigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarbecovirus may have the ability to infect lymphocytes using a different way than the spike protein. In addition to inducing the death of lymphocytes, thus drastically reducing their population and causing a serious immune deficiency, allows it to remain hidden for long periods of latency using them as a viral reservoir in what is named Long-Covid Disease. Exploring possibilities, the hypothesis is focused on that N protein may be the key of infecting lymphocytes.

METHOD: The present article exhibits a computational assay for the latest complete sequences reported to GISAID, correlating N genotypes with an enhancement in the affinity of the complex that causes immune deficiency in order to determine a good docking with the N protein and some receptors in lymphocytes.

RESULTS: A novel high-interaction coupling of N-RBD and CD147 is presented as the main way of infecting lymphocytes, allowing to define those genotypes involved in their affinity enhancement.

CONCLUSION: The hypothesis is consistent with the mutagenic deriving observed on the in-silico assay, which reveals that genotypes N/120 and N/152 are determinant to reduce the Immune Response of the host infecting lymphocytes, allowing the virus persists indefinitely and causing an Acquire Immune Deficiency Syndrome.}, } @article {pmid37602544, year = {2024}, author = {Ghosh, S and Kumar, A and Pandey, SK and Kumar, S}, title = {Association of Sleep Quality With Fatigue in Post-COVID-19 Patients in an Indian Population.}, journal = {American journal of physical medicine & rehabilitation}, volume = {103}, number = {3}, pages = {188-193}, doi = {10.1097/PHM.0000000000002332}, pmid = {37602544}, issn = {1537-7385}, mesh = {Middle Aged ; Humans ; Sleep Quality ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Fatigue/epidemiology/etiology ; Pain/complications ; Sleep ; *Sleep Wake Disorders/etiology/complications ; }, abstract = {OBJECTIVE: The aims of the study are to assess the quality of sleep in recently recovered COVID-19 and long-COVID cases and to determine its associations with fatigue and pain.

METHODS: Post-COVID-19 cases (n = 201) and controls (n = 206) were assessed using the Pittsburgh Sleep Quality Index questionnaire for sleep quality, Fatigue Severity Scale for fatigue, and Numeric Pain Rating Scale for pain in this observational study.

RESULTS: Global Pittsburgh Sleep Quality Index score was higher (P ≤ 0.001) among cases (5.7 ± 5.1; 95% confidence interval, 5.0-6.4) than controls (2.1 ± 2.0; 95% confidence interval, 1.8-2.4). Normal sleep latency was observed in 56 (27.9%) patients and 164 (79.6%) controls (P < 0.001). Fatigue Severity Scale score was higher (P ≤ 0.001) among cases (16.8 ± 10.2; 95% confidence interval, 15.4, 18.2) against controls (10.9 ± 4.1; 95% confidence interval, 10.3-11.4). The Fatigue Severity Scale scores in mild, moderate, and severe COVID-19 were 14.3 ± 8.1, 22.1 ± 10.8, and 22.8 ± 13, respectively (P < 0.001) and higher in the older (20.7 ± 12.1) and middle-aged (19.6 ± 10.3) than in younger (13.9 ± 8.3) (P ≤ 0.001) cases. The global Pittsburgh Sleep Quality Index score was positively correlated with the Fatigue Severity Scale (r = 0.755, P < 0.001) and Numeric Pain Rating Scale scores (r = 0.657, P < 0.001). Numeric Pain Rating Scale score correlated with Fatigue Severity Scale score (r = 0.710, P < 0.001). Fatigue Severity Scale and global Pittsburgh Sleep Quality Index scores were higher in the long-COVID group (P < 0.001).

CONCLUSIONS: Significantly poor sleep quality was observed in post-COVID-19 individuals including long COVID being positively associated with fatigue and pain.}, } @article {pmid37602529, year = {2024}, author = {Perlaki, G and Darnai, G and Arató, Á and Alhour, HA and Szente, A and Áfra, E and Nagy, SA and Horváth, R and Kovács, N and Dóczi, T and Orsi, G and Janszky, J}, title = {Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {59}, number = {6}, pages = {2152-2161}, doi = {10.1002/jmri.28970}, pmid = {37602529}, issn = {1522-2586}, support = {TKP-2021-EGA-13//Development and Innovation Fund of Hungary's Thematic Excellence Programmes/ ; TKP2021-EGA-16//Development and Innovation Fund of Hungary's Thematic Excellence Programmes/ ; 2017-1.2.1-NKP-2017-00002//Hungarian Brain Research Program/ ; //Magyar Tudományos Akadémia/ ; K_22-142479//OTKA/ ; }, mesh = {Humans ; *COVID-19/diagnostic imaging ; Male ; Female ; *Magnetic Resonance Imaging/methods ; Adult ; Prospective Studies ; *Gray Matter/diagnostic imaging/pathology ; Young Adult ; SARS-CoV-2 ; Neuropsychological Tests ; Case-Control Studies ; Brain/diagnostic imaging/pathology ; }, abstract = {BACKGROUND: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings.

PURPOSE: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination.

STUDY TYPE: Prospective.

POPULATION: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23).

FIELD STRENGTH/SEQUENCE: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo.

ASSESSMENT: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire.

STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance.

RESULTS: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η[2] p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η[2] p = 0.101), lower subcortical gray matter (57881 ± 3998 mm[3] vs. 60470 ± 5211 mm[3], η[2] p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm[3] vs. 60.98 ± 15.8 mm[3], η[2] p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η[2] = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η[2] = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η[2] p = 0.112).

DATA CONCLUSION: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.}, } @article {pmid37599993, year = {2023}, author = {Jegatheeswaran, L and Gokani, SA and Luke, L and Klyvyte, G and Espehana, A and Garden, EM and Tarantino, A and Al Omari, B and Philpott, CM}, title = {Assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1165329}, pmid = {37599993}, issn = {1662-4548}, abstract = {PURPOSE OF REVIEW: To provide a detailed overview of the assessment of COVID-19-related olfactory dysfunction and its association with psychological, neuropsychiatric, and cognitive symptoms.

RECENT FINDINGS: COVID-19-related olfactory dysfunction can have a detrimental impact to the quality of life of patients. Prior to the COVID-19 pandemic, olfactory and taste disorders were a common but under-rated, under-researched and under-treated sensory loss. The pandemic has exacerbated the current unmet need for accessing good healthcare for patients living with olfactory disorders and other symptoms secondary to COVID-19. This review thus explores the associations that COVID-19 has with psychological, neuropsychiatric, and cognitive symptoms, and provide a framework and rationale for the assessment of patients presenting with COVID-19 olfactory dysfunction.

SUMMARY: Acute COVID-19 infection and long COVID is not solely a disease of the respiratory and vascular systems. These two conditions have strong associations with psychological, neuropsychiatric, and cognitive symptoms. A systematic approach with history taking and examination particularly with nasal endoscopy can determine the impact that this has on the patient. Specific olfactory disorder questionnaires can demonstrate the impact on quality of life, while psychophysical testing can objectively assess and monitor olfaction over time. The role of cross-sectional imaging is not yet described for COVID-19-related olfactory dysfunction. Management options are limited to conservative adjunctive measures, with some medical therapies described.}, } @article {pmid37599906, year = {2023}, author = {Owen, R and Ashton, REM and Ferraro, FV and Skipper, L and Bewick, T and Leighton, P and Phillips, BE and Faghy, MA}, title = {Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach.}, journal = {EClinicalMedicine}, volume = {62}, number = {}, pages = {102145}, pmid = {37599906}, issn = {2589-5370}, abstract = {BACKGROUND: Current approaches to support patients living with post-COVID condition, also known as Long COVID, are highly disparate with limited success in managing or resolving a well-documented and long-standing symptom burden. With approximately 2.1 million people living with the condition in the UK alone and millions more worldwide, there is a desperate need to devise support strategies and interventions for patients.

METHODS: A three-round Delphi consensus methodology was distributed internationally using an online survey and was completed by healthcare professionals (including clinicians, physiotherapists, and general practitioners), people with long COVID, and long COVID academic researchers (round 1 n = 273, round 2 n = 186, round 3 n = 138). Across the three rounds, respondents were located predominantly in the United Kingdom (UK), with 17.3-15.2% (round 1, n = 47; round 2 n = 32, round 2 n = 21) of respondents located elsewhere (United States of America (USA), Austria, Malta, United Arab Emirates (UAE), Finland, Norway, Malta, Netherlands, Iceland, Canada, Tunisie, Brazil, Hungary, Greece, France, Austrailia, South Africa, Serbia, and India). Respondents were given ∼5 weeks to complete the survey following enrolment, with round one taking place from 02/15/2022 to 03/28/22, round two; 05/09/2022 to 06/26/2022, and round 3; 07/14/2022 to 08/09/2022. A 5-point Likert scale of agreement was used and the opportunity to include free text responses was provided in the first round.

FINDINGS: Fifty-five statements reached consensus (defined as >80% agree and strongly agree), across the domains of i) long COVID as a condition, ii) current support and care available for long COVID, iii) clinical assessments for long COVID, and iv) support mechanisms and rehabilitation interventions for long COVID, further sub-categorised by consideration, inclusion, and focus. Consensus reached proposes that long COVID requires specialised, comprehensive support mechanisms and that interventions should form a personalised care plan guided by the needs of the patients. Supportive approaches should focus on individual symptoms, including but not limited to fatigue, cognitive dysfunction, and dyspnoea, utilising pacing, fatigue management, and support returning to daily activities. The mental impact of living with long COVID, tolerance to physical activity, emotional distress and well-being, and research of pre-existing conditions with similar symptoms, such as myalgic encephalomyelitis, should also be considered when supporting people with long COVID.

INTERPRETATION: We provide an outline that achieved consensus with stakeholders that could be used to inform the design and implementation of bespoke long COVID support mechanisms.

FUNDING: None.}, } @article {pmid37598150, year = {2023}, author = {Bergersen, KV and Pham, K and Li, J and Ulrich, MT and Merrill, P and He, Y and Alaama, S and Qiu, X and Harahap-Carrillo, IS and Ichii, K and Frost, S and Kaul, M and Godzik, A and Heinrich, EC and Nair, MG}, title = {Health disparities in COVID-19: immune and vascular changes are linked to disease severity and persist in a high-risk population in Riverside County, California.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1584}, pmid = {37598150}, issn = {1471-2458}, support = {R01 DA052209/DA/NIDA NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; U54 MD013368/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; California/epidemiology ; Patient Acuity ; }, abstract = {BACKGROUND: Health disparities in underserved communities, such as inadequate healthcare access, impact COVID-19 disease outcomes. These disparities are evident in Hispanic populations nationwide, with disproportionately high infection and mortality rates. Furthermore, infected individuals can develop long COVID with sustained impacts on quality of life. The goal of this study was to identify immune and endothelial factors that are associated with COVID-19 outcomes in Riverside County, a high-risk and predominantly Hispanic community, and investigate the long-term impacts of COVID-19 infection.

METHODS: 112 participants in Riverside County, California, were recruited according to the following criteria: healthy control (n = 23), outpatients with moderate infection (outpatient, n = 33), ICU patients with severe infection (hospitalized, n = 33), and individuals recovered from moderate infection (n = 23). Differences in outcomes between Hispanic and non-Hispanic individuals and presence/absence of co-morbidities were evaluated. Circulating immune and vascular biomarkers were measured by ELISA, multiplex analyte assays, and flow cytometry. Follow-up assessments for long COVID, lung health, and immune and vascular changes were conducted after recovery (n = 23) including paired analyses of the same participants.

RESULTS: Compared to uninfected controls, the severe infection group had a higher proportion of Hispanic individuals (n = 23, p = 0.012) than moderate infection (n = 8, p = 0.550). Disease severity was associated with changes in innate monocytes and neutrophils, lymphopenia, disrupted cytokine production (increased IL-8 and IP-10/CXCL10 but reduced IFNλ2/3 and IFNγ), and increased endothelial injury (myoglobin, VCAM-1). In the severe infection group, a machine learning model identified LCN2/NGAL, IL-6, and monocyte activation as parameters associated with fatality while anti-coagulant therapy was associated with survival. Recovery from moderate COVID infection resulted in long-term immune changes including increased monocytes/lymphocytes and decreased neutrophils and endothelial markers. This group had a lower proportion of co-morbidities (n = 8, p = 1.0) but still reported symptoms associated with long COVID despite recovered pulmonary function.

CONCLUSION: This study indicates increased severity of COVID-19 infection in Hispanic individuals of Riverside County, California. Infection resulted in immunological and vascular changes and long COVID symptoms that were sustained for up to 11 months, however, lung volume and airflow resistance was recovered. Given the immune and behavioral impacts of long COVID, the potential for increased susceptibility to infections and decreased quality of life in high-risk populations warrants further investigation.}, } @article {pmid37597894, year = {2023}, author = {Giaglis, S}, title = {Poised to cast wide NETs in long COVID.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {9}, pages = {2362-2364}, doi = {10.1016/j.jtha.2023.06.005}, pmid = {37597894}, issn = {1538-7836}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37596541, year = {2023}, author = {Willems, S and Didone, V and Cabello Fernandez, C and Delrue, G and Slama, H and Fery, P and Goin, J and Della Libera, C and , and Collette, F}, title = {COVCOG: Immediate and long-term cognitive improvement after cognitive versus emotion management psychoeducation programs - a randomized trial in covid patients with neuropsychological difficulties.}, journal = {BMC neurology}, volume = {23}, number = {1}, pages = {307}, pmid = {37596541}, issn = {1471-2377}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Cognition ; Emotions ; }, abstract = {BACKGROUND: Cognitive difficulties are a frequent complaint in long COVID and persist for more than a year post- infection. There is a lack of evidence-based data on effective intervention strategies. Non-pharmacological intervention programs that are used with other neurological populations have not yet been the subject of controlled trials. COVCOG is a multicentric, randomized trial comparing cognitive intervention and a cognitive-behavioural counselling.

METHODS/DESIGN: Patients with long covid are selected and recruited at least three months post-infection. Patients are randomised in a 1:1 ratio into the cognitive (neuropsychological psychoeducation) and affective (emotion management with cognitive-behavioural counselling) intervention arms. The inclusion of 130 patients is planned. The cognitive intervention includes psycho-educational modules on fatigue and sleep, attention and working memory, executive functions and long-term memory. The affective intervention includes modules on emotion recognition and communication, uncertainty management and behavioral activation. The main objective is to reduce cognitive complaints 2 months after the intervention. A Follow-up is also planned at 8 months.

DISCUSSION: Given the long-term effects of Covid on cognition and the negative effects of cognitive impairment on quality of life and social participation, it is important to determine whether low-dose, non-pharmacological interventions can be effective. The trial will determine which of the usual types of intervention is the most effective.

TRIAL REGISTRATION: Clinicaltrials.gov Number: NCT05167266 (21/12/ 2021).}, } @article {pmid37595965, year = {2023}, author = {Brown, RL and Benjamin, L and Lunn, MP and Bharucha, T and Zandi, MS and Hoskote, C and McNamara, P and Manji, H}, title = {Pathophysiology, diagnosis, and management of neuroinflammation in covid-19.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {e073923}, doi = {10.1136/bmj-2022-073923}, pmid = {37595965}, issn = {1756-1833}, mesh = {Humans ; Neuroinflammatory Diseases ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Stroke ; COVID-19 Testing ; }, abstract = {Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up.}, } @article {pmid37595619, year = {2023}, author = {Rutsch, M and Deck, R}, title = {[Occupational Stress of Long Covid Rehabilitants and Return to Work After Pneumological Rehabilitation].}, journal = {Die Rehabilitation}, volume = {62}, number = {6}, pages = {369-378}, doi = {10.1055/a-2105-5810}, pmid = {37595619}, issn = {1439-1309}, mesh = {Humans ; Female ; Middle Aged ; Adolescent ; Young Adult ; Adult ; Aged ; Male ; Return to Work ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19 ; Germany/epidemiology ; *Occupational Stress ; }, abstract = {BACKGROUND: The Long Covid syndrome, a condition that is induced by SARS-CoV-2, affects patients in their social and professional life due to persistent symptoms and functional deficits. Medical rehabilitation aims to reduce participation incapacity and restore the ability to work. So far, it is not known what happens to the occupational situation of people affected by Long Covid after pneumological rehabilitation.

METHODS: The overall study is designed as a multicentric and prospective observational study with a mixed-method design. Covid-19 rehabilitation patients undergoing pneumological rehabilitation aged between 18 and 65 years were recruited. The questionnaire data of persons that were employed at baseline were evaluated. The written survey took place at the beginning and at end of rehabilitation and, additionally, after six months. The data collected included terms such as return to work, occupational stress and changes, subjective prognosis of gainful employment (SPE scale) and occupational performance and working ability (WAI).

RESULTS: The sample comprised N=173 participants (68.2% female) and the average age was 52.5 years. 85.5% of the rehabilitation patients were fit for work six months after rehabilitation and returned to a job. Absenteeism, subjectively perceived performance, and work ability improved statistically significantly over time (p<0.01). The risk of early retirement still existed six months after rehabilitation in 41.3% of the study participants. The participation limitations were statistically significantly reduced during the follow-up with a medium effect size (ES=0.60, p<0.01). In the logistic regression, the WAI proved to be a significantly protective predictor of return to work, while cognitive corona symptoms and high levels of cognitive fatigue proved to be risk factors.

CONCLUSION: The majority of rehabilitation patients are gainfully employed six months after pneumological rehabilitation, although persistent symptoms and a reduced ability to work are also reported even after rehabilitation. In the rehabilitation of employed persons, work-related elements, for example clarification of work-related questions and preparation for occupational demands (e. g. concentration, stress, physical demands), could support a sustained return to work.}, } @article {pmid37595172, year = {2023}, author = {Riepl, M and Kaiser, J}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {4}, pages = {284-293}, pmid = {37595172}, issn = {1092-4221}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {People infected by severe acute respiratory coronavirus 2 (SARS-CoV-2) risk the development of not only acute coronavirus- disease-2019 (COVID-19) - the signs and symptoms of which range from none to severe illness that requires intensive treatment - but also long COVID (i.e., chronic COVID), a cyclical, progressive, multiphasic illness characterized by myriad debilitating conditions that persist long term. In some patients, those sequelae result in psychiatric disorders that can lead to suicide or other forms of self-harm, incidences of which have increased exponentially since before the COVID pandemic. It has been suggested that long COVID develops in an estimated 10% to 35% of people diagnosed as having COVID-19. Because the success of therapy for either form of COVID can be complicated by each patient's pharmacogenomic profile, personal treatment preferences, medical needs, and/or dosing requirements, we have found that in some people so afflicted, manufactured medications are ineffective or intolerable, and that for those individuals, a customized compound often provides relief and promotes recovery. The primary focus of this article is long COVID. The pathogenesis of that disease is reviewed, therapies for the signs and symptoms it engenders are examined, and 2 compounded formulations effective in treating both acute and chronic COVID-19 are presented.}, } @article {pmid37594232, year = {2023}, author = {Jennings, S and Corrin, T and Waddell, L}, title = {A systematic review of the evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition.}, journal = {Epidemiology and infection}, volume = {151}, number = {}, pages = {e145}, pmid = {37594232}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Vaccination/adverse effects ; Uncertainty ; }, abstract = {Post COVID-19 condition (PCC) refers to persistent or recurring symptoms (>8 weeks) occurring ≤12 weeks following acute COVID-19. The objective of this systematic review was to assess the evidence on the risk of PCC with vaccination before or after COVID-19 or after developing PCC, and the safety of vaccination among those already experiencing PCC. A search was conducted up to 13 December 2022 and standard systematic review methodology was followed. Thirty-one observational studies were included. There is moderate confidence that two doses of vaccine given pre-infection reduced the odds of PCC (pooled OR (pOR) 0.67, 95% CI 0.60-0.74, I2 = 59.9%), but low confidence that one dose may not reduce the odds (pOR 0.64, 95% CI 0.31#x2013;1.31, I2 = 99.2%), and the evidence is very uncertain about the effect of three doses (pOR 0.45, 95% CI 0.10#x2013;1.99, I2 = 30.9%). One of three studies suggested vaccination shortly after COVID-19 may offer additional protection from developing PCC compared to unvaccinated individuals, but this evidence was very uncertain. For those with PCC, vaccination was not associated with worsening PCC symptoms (10 studies) and appears safe (3 studies), but it is unclear if vaccination may change established PCC symptoms.}, } @article {pmid37592162, year = {2023}, author = {di Filippo, L and Frara, S and Terenzi, U and Nannipieri, F and Locatelli, M and Ciceri, F and Giustina, A}, title = {Lack of vitamin D predicts impaired long-term immune response to COVID-19 vaccination.}, journal = {Endocrine}, volume = {82}, number = {3}, pages = {536-541}, pmid = {37592162}, issn = {1559-0100}, mesh = {Humans ; Middle Aged ; Vitamin D ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19/prevention & control ; Vitamins ; Vaccination ; *Vitamin D Deficiency ; Immunity ; }, abstract = {PURPOSE: Low vitamin D levels were reported to negatively influence the outcome of acute COVID-19, as well as to be linked to Long-COVID. However, few studies have investigated, so far, its effects on humoral-response to anti-SARS-CoV-2 vaccination, reporting conflicting results. We aimed to evaluate the impact of baseline 25(OH)vitamin D (25(OH)D) levels on humoral-response to a two-dose cycle of Pfizer-BioNTech-vaccine up to 9-10 months after immunization.

METHODS: We retrospectively included 119 consecutive healthcare-workers (median age 53 years) without a previous history of acute COVID-19 or anti-SARS-CoV-2 immunoglobulins presence immunized with two doses of Comirnaty-vaccine from January to February 2021. 25(OH)D was measured at time of first-immunization. Immune response was evaluated at: time 0 (T0), before the first-dose; T1, time of second-dose (21 days after T0); T2, T3, T4 at 1, 5 and 9 months after T1, respectively.

RESULTS: Median 25(OH)D levels were 25.6 ng/mL, and vitamin D deficiency (25(OH)D <20 ng/mL) was observed in 29 subjects (24.8%). In those with vitamin D deficiency, we found a non-significant trend towards lower antibody-titers at T3, and significantly lower titers at T4 as compared to those not vitamin D-deficient, also observing a more pronounced antibody-titers negative drop from peak-T2 and T4 in those with vitamin D deficiency. A positive correlation between 25(OH)D levels and antibody-titers at T4 (p = 0.043) was found. In multiple linear-regression analysis, 25(OH)D deficiency and older-age resulted as negative independent factors associated with antibody titer at T4 (p = 0.026, p = 0.004; respectively).

CONCLUSION: In our relatively young cohort presenting low prevalence of hypovitaminosis D, the long-term humoral response to anti-SARS-CoV-2 vaccination was negatively influenced by low baseline 25(OH)D. Vitamin D supplementation could be tested as a strategy to optimize the vaccination campaigns to prevent severe COVID-19.}, } @article {pmid37591109, year = {2023}, author = {Dong, Q and Yang, Y and Ma, M and Ou, W and Lv, G and Huang, M and Li, Y and Lu, Y and Fan, A and Ju, Y and Zhang, Y}, title = {Posttraumatic stress symptoms in healthcare workers during the COVID-19 pandemic: A four-wave longitudinal study.}, journal = {Psychiatry research}, volume = {327}, number = {}, pages = {115406}, doi = {10.1016/j.psychres.2023.115406}, pmid = {37591109}, issn = {1872-7123}, mesh = {Humans ; Female ; Male ; *COVID-19 ; Pandemics ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; *Stress Disorders, Post-Traumatic/epidemiology ; Health Personnel ; }, abstract = {BACKGROUND: Posttraumatic stress symptoms of healthcare workers have become a significant public concern in the healthcare system that have long COVID-19. It is less known how the pandemic impacts the HCWs' PTSS longitudinally and long-term risk factors for it.

METHODS: Four consecutive surveys were conducted among healthcare workers in China from 2019 to 2023 COVID-19 outbreaks. Multilevel mixed-effect models were used to examine longitudinal changes and risk factors. Network analysis was utilized to explore network centrality changes in PTSS symptoms.

RESULTS: HCWs' PTSS symptoms were increased over time during the COVID-19 pandemic. Being female, being nurse, working in the emergency department, working longer hours, less frequently going back home and having COVID-19 infection are risk factors of PTSS for HCWs; unmarried is the protective factor. Significant interaction between symptom changes and profession exists. PTSS networks showed that Avoidance of thoughts, Emotional-cue activity, Exaggerated startle response and Hypervigilance were the central symptoms during four waves. The global strength of the PTSS network grows over time, and nodal strength of Avoidance of thoughts, Loss of interest and Negative beliefs increased by COVID-19.

CONCLUSION: The pandemic's impacts on healthcare workers vary by professions. PTSS symptoms exacerbate, reinforce each other, and persists with recurring waves.}, } @article {pmid37588623, year = {2023}, author = {Moor, M and Bennett, N and Plečko, D and Horn, M and Rieck, B and Meinshausen, N and Bühlmann, P and Borgwardt, K}, title = {Predicting sepsis using deep learning across international sites: a retrospective development and validation study.}, journal = {EClinicalMedicine}, volume = {62}, number = {}, pages = {102124}, pmid = {37588623}, issn = {2589-5370}, abstract = {BACKGROUND: When sepsis is detected, organ damage may have progressed to irreversible stages, leading to poor prognosis. The use of machine learning for predicting sepsis early has shown promise, however international validations are missing.

METHODS: This was a retrospective, observational, multi-centre cohort study. We developed and externally validated a deep learning system for the prediction of sepsis in the intensive care unit (ICU). Our analysis represents the first international, multi-centre in-ICU cohort study for sepsis prediction using deep learning to our knowledge. Our dataset contains 136,478 unique ICU admissions, representing a refined and harmonised subset of four large ICU databases comprising data collected from ICUs in the US, the Netherlands, and Switzerland between 2001 and 2016. Using the international consensus definition Sepsis-3, we derived hourly-resolved sepsis annotations, amounting to 25,694 (18.8%) patient stays with sepsis. We compared our approach to clinical baselines as well as machine learning baselines and performed an extensive internal and external statistical validation within and across databases, reporting area under the receiver-operating-characteristic curve (AUC).

FINDINGS: Averaged over sites, our model was able to predict sepsis with an AUC of 0.846 (95% confidence interval [CI], 0.841-0.852) on a held-out validation cohort internal to each site, and an AUC of 0.761 (95% CI, 0.746-0.770) when validating externally across sites. Given access to a small fine-tuning set (10% per site), the transfer to target sites was improved to an AUC of 0.807 (95% CI, 0.801-0.813). Our model raised 1.4 false alerts per true alert and detected 80% of the septic patients 3.7 h (95% CI, 3.0-4.3) prior to the onset of sepsis, opening a vital window for intervention.

INTERPRETATION: By monitoring clinical and laboratory measurements in a retrospective simulation of a real-time prediction scenario, a deep learning system for the detection of sepsis generalised to previously unseen ICU cohorts, internationally.

FUNDING: This study was funded by the Personalized Health and Related Technologies (PHRT) strategic focus area of the ETH domain.}, } @article {pmid37587244, year = {2024}, author = {Reuken, PA and Besteher, B and Finke, K and Fischer, A and Holl, A and Katzer, K and Lehmann-Pohl, K and Lemhöfer, C and Nowka, M and Puta, C and Walter, M and Weißenborn, C and Stallmach, A}, title = {Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1903-1910}, pmid = {37587244}, issn = {1433-8491}, support = {2021 FGI 0060//Thüringer Aufbaubank/ ; }, mesh = {Humans ; *COVID-19/complications/psychology ; *Registries ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Germany/epidemiology ; Aged ; Fatigue/etiology ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed. A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening. A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.}, } @article {pmid37586358, year = {2024}, author = {Zhou, S and Zhang, A and Liao, H and Liu, Z and Yang, F}, title = {Pathological Interplay and Clinical Complications between COVID-19 and Cardiovascular Diseases: An Overview in 2023.}, journal = {Cardiology}, volume = {149}, number = {1}, pages = {60-70}, pmid = {37586358}, issn = {1421-9751}, mesh = {Humans ; *COVID-19/complications ; *Cardiovascular Diseases/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Arrhythmias, Cardiac/complications ; Myocytes, Cardiac ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) involves all organs of the body, of which the interaction with cardiovascular diseases is the most important.

SUMMARY: Numerous studies have reported that COVID-19 patients complicated with cardiovascular comorbidities (hypertension, coronary heart disease, chronic heart failure (HF), cerebrovascular disease) are more likely to develop into critical illness and have higher mortality. Conversely, COVID-19 may also cause myocardial injury in patients through various pathological mechanisms such as direct virus attack on cardiomyocytes, overactivation of immune response, microthrombus formation, which may lead to fatal acute ST-segment elevation myocardial infarction, arrhythmia, acute worsening of chronic HF, etc. In addition, the symptoms of the so-called long-COVID may remain in some patients who survived the acute viral infection. Positional tachycardia has been widely reported, and cardiovascular autonomic disorders are thought to play a pathogenic role.

KEY MESSAGE: The review summarizes the interaction between COVID-19 and cardiovascular disease in terms of pathological mechanism, clinical features, and sequelae. Therapeutic and rehabilitation programs after COVID-19 infection are compiled and need to be further standardized in the future.}, } @article {pmid37586104, year = {2024}, author = {Zheng, C and Chen, XK and Sit, CH and Liang, X and Li, MH and Ma, AC and Wong, SH}, title = {Effect of Physical Exercise-Based Rehabilitation on Long COVID: A Systematic Review and Meta-analysis.}, journal = {Medicine and science in sports and exercise}, volume = {56}, number = {1}, pages = {143-154}, pmid = {37586104}, issn = {1530-0315}, mesh = {Humans ; Female ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise Therapy ; Exercise ; }, abstract = {PURPOSE: The number of persons living with post-coronavirus disease 2019 (COVID-19) conditions or long COVID continues to rise worldwide; however, the etiology and the treatment of long COVID remain nebulous. Therefore, efficient, feasible, and cost-effective therapeutic strategies for a large population with long COVID remain warranted. Physical exercise-based rehabilitation is a promising strategy for long COVID, although its therapeutic effects remain to be determined. This systematic review and meta-analysis aimed to examine the effects of physical exercise-based rehabilitation on long COVID.

METHODS: The electronic databases Medline, Embase, Global Health (Ovid), CINAHL (EBSCO), Web of Science, WHO Global Research Database on COVID-19, LitCovid, and Google Scholar were searched from their inception to November 2022. The identified articles were independently screened by three reviewers, and a random-effects model was used to determine the mean differences in the meta-analysis.

RESULTS: Twenty-three studies involving 1579 individuals who had COVID-19 (752 women) were included. Physical exercise-based rehabilitation showed beneficial effects on long COVID-related symptoms characterized by dyspnea, fatigue, and depression, as well as on the 6-min walk test, forced expiratory volume in 1 s/forced vital capacity, and quality of life in people who had COVID-19.

CONCLUSIONS: Physical exercise-based rehabilitation is a potential therapeutic strategy against long COVID and can be applied as a routine clinical practice in people who have recovered from COVID-19. However, customized physical exercise-based rehabilitation programs and their effects on specific types of long COVID require future large-scale studies.}, } @article {pmid37585213, year = {2023}, author = {Harris, E}, title = {Federal Government Announces Long COVID Trials, Research Office.}, journal = {JAMA}, volume = {330}, number = {9}, pages = {797}, doi = {10.1001/jama.2023.13936}, pmid = {37585213}, issn = {1538-3598}, mesh = {Humans ; COVID-19 ; Federal Government ; Government ; Government Regulation ; *Post-Acute COVID-19 Syndrome ; United States ; United States Office of Research Integrity ; *Biomedical Research ; }, } @article {pmid37585091, year = {2023}, author = {Cao, S and Song, Z and Rong, J and Andrikopoulos, N and Liang, X and Wang, Y and Peng, G and Ding, F and Ke, PC}, title = {Spike Protein Fragments Promote Alzheimer's Amyloidogenesis.}, journal = {ACS applied materials & interfaces}, volume = {15}, number = {34}, pages = {40317-40329}, pmid = {37585091}, issn = {1944-8252}, support = {P20 GM121342/GM/NIGMS NIH HHS/United States ; R35 GM145409/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Aged ; *Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Pandemics ; Post-Acute COVID-19 Syndrome ; Spike Glycoprotein, Coronavirus ; Zebrafish/metabolism ; *COVID-19 ; SARS-CoV-2/metabolism ; Peptide Fragments/metabolism ; *Virus Diseases ; }, abstract = {Alzheimer's disease (AD) is a major cause of dementia inducing memory loss, cognitive decline, and mortality among the aging population. While the amyloid aggregation of peptide Aβ has long been implicated in neurodegeneration in AD, primarily through the production of toxic polymorphic aggregates and reactive oxygen species, viral infection has a less explicit role in the etiology of the brain disease. On the other hand, while the COVID-19 pandemic is known to harm human organs and function, its adverse effects on AD pathobiology and other human conditions remain unclear. Here we first identified the amyloidogenic potential of [1058]HGVVFLHVTYV[1068], a short fragment of the spike protein of SARS-CoV-2 coronavirus. The peptide fragment was found to be toxic and displayed a high binding propensity for the amyloidogenic segments of Aβ, thereby promoting the aggregation and toxicity of the peptide in vitro and in silico, while retarding the hatching and survival of zebrafish embryos upon exposure. Our study implicated SARS-CoV-2 viral infection as a potential contributor to AD pathogenesis, a little explored area in our quest for understanding and overcoming Long Covid.}, } @article {pmid37584412, year = {2024}, author = {Radmanesh, D and Powell, E and Trinh, H}, title = {Too tired to think: Relationship between post-COVID-19 fatigue and cognition in a veteran sample.}, journal = {Neuropsychological rehabilitation}, volume = {34}, number = {6}, pages = {823-844}, doi = {10.1080/09602011.2023.2244159}, pmid = {37584412}, issn = {1464-0694}, mesh = {Humans ; *Veterans ; *COVID-19/complications ; *Fatigue/etiology ; Male ; Middle Aged ; Female ; Aged ; Cognitive Dysfunction/etiology ; Adult ; Cognition/physiology ; Retrospective Studies ; Sleep Wake Disorders/etiology ; Depression/etiology ; }, abstract = {COVID-19 survivors often endorse persistent physical and neuropsychiatric problems following disease recovery, a phenomenon described as "long COVID." Research exploring long-COVID continues to evolve in large-scale studies but remains limited among smaller populations (e.g., veterans). We explored the relationship between persistent post-COVID-19 fatigue and cognition among a sample of 246 veterans who voluntarily enrolled in a COVID-19 Convalescence Programme and completed a mental health evaluation of post-illness mood (depression, anxiety, PTSD), cognition (subjective complaints, Modified Telephone Interview for Cognitive Status [TICS-M] performance), fatigue, pain, and sleep. In concert with our hypotheses, subjective cognitive complaints are not significantly correlated with TICS-M performance, but rather are strongly correlated with long-COVID fatigue. Although cognitive changes are common post-COVID complaints, these are likely better predicted by other factors, (e.g., fatigue, mood, pain, and sleep disruption). Furthermore, comorbid mood, sleep, and pain complaints appeared to mediate the relationship between subjective cognitive complaints and fatigue. Limitations to this study included use of retrospective chart review data, limited access to pre-disease data for comparison, and lack of healthy controls. Clinicians should consider the impact of modifiable conditions associated with cognitive and functional decline, as these conditions may be targets for interdisciplinary treatment in a long-COVID veteran population.}, } @article {pmid37584410, year = {2023}, author = {Kell, DB and Pretorius, E}, title = {Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?.}, journal = {The Biochemical journal}, volume = {480}, number = {15}, pages = {1217-1240}, doi = {10.1042/BCJ20230241}, pmid = {37584410}, issn = {1470-8728}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Autoimmunity ; *COVID-19 ; Amyloid/metabolism ; *Prions ; *Thrombosis ; Fibrinogen ; Amyloidogenic Proteins ; }, abstract = {It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin that is amyloid in character; the resultant clots and microclots entrap many other molecules, stain with fluorogenic amyloid stains, are rather resistant to fibrinolysis, can block up microcapillaries, are implicated in a variety of diseases including Long COVID, and have been referred to as fibrinaloids. A necessary corollary of this anomalous polymerisation is the generation of novel epitopes in proteins that would normally be seen as 'self', and otherwise immunologically silent. The precise conformation of the resulting fibrinaloid clots (that, as with prions and classical amyloid proteins, can adopt multiple, stable conformations) must depend on the existing small molecules and metal ions that the fibrinogen may (and is some cases is known to) have bound before polymerisation. Any such novel epitopes, however, are likely to lead to the generation of autoantibodies. A convergent phenomenology, including distinct conformations and seeding of the anomalous form for initiation and propagation, is emerging to link knowledge in prions, prionoids, amyloids and now fibrinaloids. We here summarise the evidence for the above reasoning, which has substantial implications for our understanding of the genesis of autoimmunity (and the possible prevention thereof) based on the primary process of fibrinaloid formation.}, } @article {pmid37583962, year = {2023}, author = {Houchen-Wolloff, L and Overton, C and Ibbetson, A and Walters, A and Hastie, C and Gill, R and Armstrong, N and Singh, S and Little, P and Evans, K and Pimm, J and Marks, M and Poinasamy, K and Walker, S and Briggs, A and Evans, RA}, title = {A typology of healthcare pathways after hospital discharge for adults with COVID-19: the evolution of UK services during pandemic conditions.}, journal = {ERJ open research}, volume = {9}, number = {4}, pages = {}, pmid = {37583962}, issn = {2312-0541}, abstract = {INTRODUCTION: Over half of post-COVID-hospitalisation adults have persistent symptoms 2 years after discharge, providing a challenge for individuals and healthcare systems. We therefore aimed to describe a typology of UK healthcare pathways post-hospital discharge as a first step towards understanding clinical effectiveness and cost-effectiveness of different healthcare pathways.

METHODS: In 2021, we surveyed hospital sites taking part in the UK Post-hospital COVID-19 (PHOSP-COVID) study. The online survey explored the availability of proactive follow-up, patient selection, involvement of multidisciplinary teams, investigations, assessment and access to mental health and rehabilitation interventions. The typology was defined by a three-stage process: 1) using the survey results to develop a bespoke algorithm to inform a draft classification, 2) a stakeholder event for refinement and 3) finalisation between the Project Advisory Group and research team. The bespoke algorithm was used to map each site onto the classification with further mapping by level of mental health and rehabilitation provision.

RESULTS: 70% of hospital sites (45 out of 64) responded to the survey. 82% (37 out of 45) reported delivering a follow-up service after hospital discharge during the first few months of the pandemic. Only 13 out of 37 services (35%) were delivered by permanent staff. The final typology of five categories included no proactive follow-up, and a matrix of four groups based on patient selection (prespecified subgroup/all patients) and complexity of assessment (low/high). The complexity of assessment, rehabilitation and mental health interventions was variable within sites.

DISCUSSION: We describe the first typology of post-hospitalisation COVID-19 healthcare pathways to enable modelling of clinical effectiveness and cost-effectiveness to inform future policy. Our results highlight the heterogeneity and vulnerability of healthcare services after COVID-19 hospitalisation.}, } @article {pmid37583958, year = {2023}, author = {Li, Z and Zhang, Z and Zhang, Z and Wang, Z and Li, H}, title = {Cognitive impairment after long COVID-19: current evidence and perspectives.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1239182}, pmid = {37583958}, issn = {1664-2295}, abstract = {COVID-19, caused by the SARS-CoV-2 virus, is a respiratory infectious disease. While most patients recover after treatment, there is growing evidence that COVID-19 may result in cognitive impairment. Recent studies reveal that some individuals experience cognitive deficits, such as diminished memory and attention, as well as sleep disturbances, suggesting that COVID-19 could have long-term effects on cognitive function. Research indicates that COVID-19 may contribute to cognitive decline by damaging crucial brain regions, including the hippocampus and anterior cingulate cortex. Additionally, studies have identified active neuroinflammation, mitochondrial dysfunction, and microglial activation in COVID-19 patients, implying that these factors may be potential mechanisms leading to cognitive impairment. Given these findings, the possibility of cognitive impairment following COVID-19 treatment warrants careful consideration. Large-scale follow-up studies are needed to investigate the impact of COVID-19 on cognitive function and offer evidence to support clinical treatment and rehabilitation practices. In-depth neuropathological and biological studies can elucidate precise mechanisms and provide a theoretical basis for prevention, treatment, and intervention research. Considering the risks of the long-term effects of COVID-19 and the possibility of reinfection, it is imperative to integrate basic and clinical research data to optimize the preservation of patients' cognitive function and quality of life. This integration will also offer valuable insights for responding to similar public health events in the future. This perspective article synthesizes clinical and basic evidence of cognitive impairment following COVID-19, discussing potential mechanisms and outlining future research directions.}, } @article {pmid37582798, year = {2023}, author = {Zhang, J and Luo, D and Kang, M and Li, B and Su, S}, title = {Clinical characteristics and short-term outcomes of acute pancreatitis among patients with COVID-19.}, journal = {European journal of medical research}, volume = {28}, number = {1}, pages = {283}, pmid = {37582798}, issn = {2047-783X}, mesh = {Humans ; *Pancreatitis/complications/diagnosis ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Acute Disease ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {OBJECTIVE: The existing literature on the combination of acute pancreatitis (AP) and COVID-19 is scarce. The objective of our study is to compare the clinical outcomes and occurrence of long COVID syndrome in AP patients with and without COVID-19, while investigating the potential impact of COVID-19 on the severity, mortality rate, and long COVID syndrome in these patients.

METHODS: This retrospective, observational study was conducted at a single center. It included patients aged 18 years and above who were diagnosed with AP during the pandemic. Patients were categorized into two groups based on the results of RT-qPCR testing: the SARS-CoV-2-positive group and the SARS-CoV-2-negative group. The study aimed to compare the severity of AP, mortality rate, and occurrence of long COVID syndrome between these two groups.

RESULT: A retrospective review was conducted on 122 patients diagnosed with acute pancreatitis between December 1, 2022, and January 31, 2023. Out of these patients, 100 were included in the study. The analysis revealed no significant differences in mortality rate, severity, and sequelae between AP patients with COVID-19 and those without COVID-19 (p > 0.005). However, a statistically significant difference was observed in the occurrence of long COVID syndrome, specifically in the presence of cough (p = 0.04).

CONCLUSION: This study demonstrates that the presence of COVID-19 in patients with pancreatitis does not lead to an increase in the mortality and severity rate of pancreatitis.}, } @article {pmid37581906, year = {2023}, author = {Dalko, K and Kraft, B and Jahn, P and Schildmann, J and Hofstetter, S}, title = {Cocreation of Assistive Technologies for Patients With Long COVID: Qualitative Analysis of a Literature Review on the Challenges of Patient Involvement in Health and Nursing Sciences.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e46297}, pmid = {37581906}, issn = {1438-8871}, mesh = {Humans ; Patient Participation ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Communication ; *Self-Help Devices ; }, abstract = {BACKGROUND: Digital assistive technologies have the potential to address the pressing need for adequate therapy options for patients with long COVID (also known as post-COVID-19 condition) by enabling the implementation of individual and independent rehabilitation programs. However, the involvement of the target patient group is necessary to develop digital devices that are closely aligned to the needs of this particular patient group.

OBJECTIVE: Participatory design approaches, such as cocreation, may be a solution for achieving usability and user acceptance. However, there are currently no set methods for implementing cocreative development processes incorporating patients. This study addresses the following research questions: what are the tasks and challenges associated with the involvement of patient groups? What lessons can be learned regarding the adequate involvement of patients with long COVID?

METHODS: First, a literature review based on a 3-stage snowball process was conducted to identify the tasks and challenges emerging in the context of the cocreation of digital assistive devices and services with patient groups. Second, a qualitative analysis was conducted in an attempt to extract relevant findings and criteria from the identified studies. Third, using the method of theory adaptation, this paper presents recommendations for the further development of the existing concepts of cocreation in relation to patients with long COVID.

RESULTS: The challenges of an active involvement of patients in cocreative development in health care include hierarchical barriers and differences in the levels of specific knowledge between professionals and patients. In the case of long COVID, patients themselves are still inexperienced in dealing with their symptoms and are hardly organized into established groups. This amplifies general hurdles and leads to questions of group identity, power structure, and knowledge creation, which are not sufficiently addressed by the current methods of cocreation.

CONCLUSIONS: The adaptation of transdisciplinary methods to cocreative development approaches focusing on collaborative and inclusive communication can address the recurring challenges of actively integrating patients with long COVID into development processes.}, } @article {pmid37581581, year = {2023}, author = {Au, L and Capotescu, C and Curi, A and Gonçalves Leonel da Silva, R and Eyal, G}, title = {Long Covid requires a global response centred on equity and dialogue.}, journal = {Global health action}, volume = {16}, number = {1}, pages = {2244757}, pmid = {37581581}, issn = {1654-9880}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Global Health ; *Social Media ; Surveys and Questionnaires ; }, abstract = {Long Covid, or Post-Covid Conditions, is a global health problem. Yet we know strikingly little about the different experiences of Long Covid patients cross-nationally. To address this shortcoming, we conducted an online survey of Long Covid patients active on social media in the U.S. (n = 334, October to December 2021) and Brazil (n = 144, January to April 2022). Our analysis of short answer responses indicates patient dissatisfaction with medical care provided for Long Covid in both the U.S. and Brazil. For Long Covid patients in Brazil, there were additional concerns raised about the lack of local expertise about their condition. Based on these results, we urge policymakers to expand the education of medical professionals in order to raise awareness of Long Covid. Experts in the Global North should also be encouraged to engage in dialogue with patient groups and experts in the Global South, in order to better understand how local contexts shape the experience of Long Covid.}, } @article {pmid37581327, year = {2023}, author = {Fajloun, Z and Wu, Y and Cao, Z and Kovacic, H and Sabatier, JM}, title = {COVID-19: Potassium Contributes to Pathologies that Cause Disability.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {7}, pages = {39-41}, doi = {10.2174/1871526523666230529163610}, pmid = {37581327}, issn = {2212-3989}, mesh = {Humans ; *COVID-19 ; Potassium ; SARS-CoV-2 ; Renin-Angiotensin System ; }, } @article {pmid37808250, year = {2022}, author = {Zhou, X and Zhang, K and Liu, L and Zhao, Q and Huang, M and Shao, R and Wang, Y and Qu, B and Wang, Y}, title = {Anti-fatigue effect from Ginseng Radix et Rhizoma: a suggestive and promising treatment for long COVID.}, journal = {Acupuncture and herbal medicine}, volume = {2}, number = {2}, pages = {69-77}, pmid = {37808250}, issn = {2765-8619}, abstract = {Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients. Ginseng Radix et Rhizoma-known as the King of Herbs in traditional Chinese medicine-has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially in regard to targeting fatigue.}, } @article {pmid38283613, year = {2022}, author = {Goldberg, NC and Poirier, S and Kanas, A and McCorkell, L and McGinn, CA and Re'em, Y and Kuehnel, K and Muirhead, N and Ruschioni, T and Taylor-Brown, S and Jason, LA}, title = {A new clinical challenge: supporting patients coping with the long-term effects of COVID-19.}, journal = {Fatigue : biomedicine, health & behavior}, volume = {10}, number = {4}, pages = {212-230}, pmid = {38283613}, issn = {2164-1846}, support = {U24 NS105535/NS/NINDS NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; }, abstract = {Mental Health Practitioners (MHPs) have a unique opportunity to provide resources and support to those suffering from Long COVID (LC), the post infectious illness that often follows an acute SARS-CoV-2 infection. In working with these individuals, MHPs can learn from the experiences of patients with another post-infectious disease known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS was once thought to be a psychologically mediated disorder caused by deconditioning and the fear of exertion following a precipitating event such as a viral infection. Research now shows that LC and ME/CFS are biomedical, multisystem, complex physiologic diseases. This article provides a framework to MHPs for the treatment of LC patients using knowledge derived from three decades of research on ME/CFS.}, } @article {pmid37718637, year = {2021}, author = {}, title = {NewsCAP: Growing concern about the risk of 'long COVID' in children.}, journal = {The American journal of nursing}, volume = {121}, number = {6}, pages = {15}, doi = {10.1097/01.NAJ.0000753612.88791.f5}, pmid = {37718637}, issn = {1538-7488}, } @article {pmid37638236, year = {2021}, author = {Zhang, LM and Symalla, T and Roggin, KK and Matthews, JB and Hussain, M}, title = {Creation of a COVID-19 Based Educational Curriculum: A Blueprint for Redesigning Surgical Education During Times of National Crisis.}, journal = {Annals of surgery open : perspectives of surgical history, education, and clinical approaches}, volume = {2}, number = {1}, pages = {e042}, pmid = {37638236}, issn = {2691-3593}, abstract = {OBJECTIVE: To create a COVID-19 based educational curriculum for surgical residents.

BACKGROUND DATA: The COVID-19 pandemic has resulted in disruptions to operative volume and clinical education for surgery residents. This has placed a greater importance on didactic education. However, in the face of pandemic-related uncertainty, focusing on a traditional educational curriculum may be a challenge for surgical residents.

METHODS: A dedicated resident educational team was created. This team identified specific surgical resident needs, evaluated institutional resources, created a curriculum and timeline, determined a feasible implementation format, and assessed resident opinions on the impact of the curriculum via anonymous survey.

RESULTS: A 1-month long COVID-19 based curriculum was developed, which covered (1) advanced critical care and resuscitation techniques pertinent to patients with COVID-19, (2) institutional physician experience in the COVID-units, (3) ethical dilemmas in resource management, (4) triaging of operative cases during the pandemic, and (5) published and ongoing COVID-19-related surgical research. In the postimplementation survey, a majority of residents reported that the curriculum helped improve their ability to take care of patients during the pandemic, provided an opportunity for questions, alleviated anxieties and concerns, and that they preferred the COVID-19 curriculum over traditional surgical topics.

CONCLUSIONS: In the midst of national crisis and significant clinical disruption, real-time adjustments to surgical education can and should occur to address resident needs. The results of our study may serve as a blueprint for implementing rapid change to resident education in the future.}, } @article {pmid37579159, year = {2023}, author = {Wang, PY and Ma, J and Kim, YC and Son, AY and Syed, AM and Liu, C and Mori, MP and Huffstutler, RD and Stolinski, JL and Talagala, SL and Kang, JG and Walitt, BT and Nath, A and Hwang, PM}, title = {WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {34}, pages = {e2302738120}, pmid = {37579159}, issn = {1091-6490}, support = {Z01 HL005101/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Female ; Humans ; Mice ; *COVID-19/metabolism ; *Fatigue Syndrome, Chronic/diagnosis ; Mitochondria/metabolism ; Post-Acute COVID-19 Syndrome ; Respiration ; Wiskott-Aldrich Syndrome Protein Family/metabolism ; Mice, Transgenic ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), here identified in a 38-y-old woman suffering from long-standing fatigue and exercise intolerance, can disrupt mitochondrial respiratory supercomplex formation and is associated with endoplasmic reticulum (ER) stress. Increased expression of WASF3 in transgenic mice markedly decreased their treadmill running capacity with concomitantly impaired respiratory supercomplex assembly and reduced complex IV levels in skeletal muscle mitochondria. WASF3 induction by ER stress using endotoxin, well known to be associated with fatigue in humans, also decreased skeletal muscle complex IV levels in mice, while decreasing WASF3 levels by pharmacologic inhibition of ER stress improved mitochondrial function in the cells of the patient with chronic fatigue. Expanding on our findings, skeletal muscle biopsy samples obtained from a cohort of patients with ME/CFS showed increased WASF3 protein levels and aberrant ER stress activation. In addition to revealing a potential mechanism for the bioenergetic deficiency in ME/CFS, our study may also provide insights into other disorders associated with fatigue such as rheumatic diseases and long COVID.}, } @article {pmid37577714, year = {2023}, author = {Peluso, MJ and Ryder, D and Flavell, R and Wang, Y and Levi, J and LaFranchi, BH and Deveau, TM and Buck, AM and Munter, SE and Asare, KA and Aslam, M and Koch, W and Szabo, G and Hoh, R and Deswal, M and Rodriguez, A and Buitrago, M and Tai, V and Shrestha, U and Lu, S and Goldberg, SA and Dalhuisen, T and Durstenfeld, MS and Hsue, PY and Kelly, JD and Kumar, N and Martin, JN and Gambir, A and Somsouk, M and Seo, Y and Deeks, SG and Laszik, ZG and VanBrocklin, HF and Henrich, TJ}, title = {Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37577714}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AI145806/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, abstract = {The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [[18]F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [[18]F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.}, } @article {pmid37577106, year = {2023}, author = {Gawey, B and Yang, J and Bauer, B and Song, J and Wang, XJ}, title = {The use of complementary and alternative medicine for the treatment of gastrointestinal symptoms in Long COVID: a systematic review.}, journal = {Therapeutic advances in chronic disease}, volume = {14}, number = {}, pages = {20406223231190548}, pmid = {37577106}, issn = {2040-6223}, abstract = {BACKGROUND: Most people with coronavirus disease 2019 (COVID-19) experience resolution of symptoms within days to weeks following initial infection. In a subset of individuals, symptoms persist longer than 4 weeks, known as 'Long COVID'. Many gastrointestinal (GI) symptoms persist as part of this syndrome; yet, an approach to treatment remains unclear. Prior studies have demonstrated the efficacy of complementary and alternative medicine (CAM) for the treatment of acute COVID-19 infections, but little data exist regarding the potential use of CAM in the treatment of Long COVID.

OBJECTIVES: Identify CAM approaches useful in treating the GI symptoms of Long COVID.

DESIGN: A systematic review of studies reporting on the use of CAM for the treatment of GI symptoms of Long COVID was performed.

DATA SOURCES AND METHODS: Five electronic databases were searched from January 2019 to November 2022. Studies describing the use of CAM to treat GI symptoms of Long COVID were included and assessed by two independent reviewers. Studies not reporting on GI symptoms or using CAM were excluded. Studies chosen for final review underwent quality and bias assessment using predetermined criteria. The extracted data were synthesized utilizing a framework derived from the National Center of Complementary and Integrative Health categories.

RESULTS: The initial search yielded 396 articles. After applying the eligibility criteria, a total of four studies (three case reports and one case series) were included for final review. Two studies used nutritional supplements and two studies used traditional Chinese medicine. Reductions in nausea, loss of appetite, diarrhea, acid reflux, epigastric pain, and bloating were reported.

CONCLUSION: This is the first systematic review to explore the role of CAM in treating GI manifestations of Long COVID. The review identified four studies, all reporting reductions in the GI symptoms of Long COVID. Despite the positive studies included in this review, the overall search yielded few results, all of which were non-experimental. As the post-infectious sequelae of COVID-19 become better recognized in the wake of the pandemic, higher-quality clinical studies are needed.}, } @article {pmid37575987, year = {2023}, author = {Sen, S and Khosla, S and Awan, O and Cohen, S and Gollie, JM}, title = {Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1197061}, pmid = {37575987}, issn = {2296-858X}, support = {I21 RX004371/RX/RRD VA/United States ; IK2 RX003423/RX/RRD VA/United States ; }, abstract = {Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.}, } @article {pmid37574270, year = {2024}, author = {Abe, K and Sugiyama, A and Ito, N and Miwata, K and Kitahara, Y and Okimoto, M and Mirzaev, U and Kurisu, A and Akita, T and Ko, K and Takahashi, K and Kubo, T and Takafuta, T and Tanaka, J}, title = {Variant-specific Symptoms After COVID-19: A Hospital-based Study in Hiroshima.}, journal = {Journal of epidemiology}, volume = {34}, number = {5}, pages = {238-246}, pmid = {37574270}, issn = {1349-9092}, mesh = {Humans ; *COVID-19/epidemiology ; Male ; Female ; Middle Aged ; Aged ; Japan/epidemiology ; *SARS-CoV-2 ; Surveys and Questionnaires ; Adult ; Cluster Analysis ; Risk Factors ; }, abstract = {BACKGROUND: Symptoms after novel coronavirus disease 2019 (COVID-19) recovery by severe acute respiratory syndrome coronavirus 2 strains are unspecified.

METHODS: This self-administered questionnaire-based study was conducted to investigate symptoms after COVID-19 recovery at one of the main hospitals for COVID-19 treatment in Hiroshima, Japan, from September 2020 to March 2022 for patients who visited follow-up consultations after COVID-19. Study subjects were divided into four groups (Wild-type, Alpha, Delta, and Omicron periods) according to COVID-19 onset date. Hierarchical cluster analysis was performed to determine symptom clusters and investigate risk factors for each symptom cluster using multivariate analysis.

RESULTS: Among 385 patients who enrolled in this study, 249 patients had any persistent symptoms at a median of 23.5 (interquartile range, 20-31) days after COVID-19 onset. Among patients with any persistent symptoms, symptom clusters including olfactory or taste disorders, respiratory symptoms, and cardiac symptoms were found. Respiratory symptoms were more frequent among patients infected in the Omicron period compared to the Wild-type period (adjusted odds ratio [AOR] 3.13; 95% confidence interval [CI], 1.31-7.48). Compared to patients who recovered from mild COVID-19, patients who needed oxygen or ventilation support suffered fewer post-COVID-19 respiratory symptoms (AOR 0.46; 95% CI, 0.22-0.97) but more post-COVID-19 cardiac symptoms among them (AOR 2.67; 95% CI, 1.26-5.65). Olfactory or taste disorders were fewer among patients infected in the Omicron period compared to the Wild-type period (AOR 0.14; 95% CI, 0.04-0.46).

CONCLUSION: This study revealed that symptoms after COVID-19 may vary depending on the infected strain.}, } @article {pmid37573677, year = {2023}, author = {Turner, M and Beckwith, H and Spratt, T and Vallejos, EP and Coughlan, B}, title = {The #longcovid revolution: A reflexive thematic analysis.}, journal = {Social science & medicine (1982)}, volume = {333}, number = {}, pages = {116130}, doi = {10.1016/j.socscimed.2023.116130}, pmid = {37573677}, issn = {1873-5347}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Europe ; *Social Media ; }, abstract = {Research has identified long COVID as the first virtual patient-made condition (Callard and Perego, 2021). It originated from Twitter users sharing their experiences using the hashtag #longcovid. Over the first two years of the pandemic, long COVID affected as many as 17 million people in Europe (WHO, 2023). This study focuses on the initial #longcovid tweets in 2020 (as previous studies have focused on 2021-2022), from the first tweet in May to August 2020, when the World Health Organization recognised the condition. We collected over 31,000 tweets containing #longcovid from Twitter. Using Braun and Clarke's reflexive thematic analysis (2020), informed by the first author's experience of long COVID and drawing on Ian Hacking's perspective on social constructionism (1999), we identified different grades of social constructionism in the tweets. The themes we generated reflected that long COVID was a multi-system, cyclical condition initially stigmatised and misunderstood. These findings align with existing literature (Ladds et al., 2020; Rushforth et al., 2021). We add to the existing literature by suggesting that Twitter users raised awareness of long COVID by providing social consensus on their long COVID symptoms. Despite the challenge for traditional evidence-based medicine to capture the varied and intermittent symptoms, the social consensus highlighted that these variations were a consistent and collective experience. This social consensus fostered a collective social movement, overcoming stigma through supportive tweets and highlighting their healthcare needs using #researchrehabrecognition. The #longcovid movement's work was revolutionary, as it showed a revolutionary grade of social constructionism, because it brought about real-world change for long COVID sufferers in terms of recognition and the potential for healthcare provisions. Twitter users' accounts expose the limitations of traditional evidence-based medicine in identifying new conditions. Future research on novel conditions should consider various research paradigms, such as Evidence-Based Medicine Plus (Greenhalgh et al., 2022).}, } @article {pmid37573421, year = {2023}, author = {Godino, JG and Samaniego, JC and Sharp, SP and Taren, D and Zuber, A and Armistad, AJ and Dezan, AM and Leyba, AJ and Friedly, JL and Bunnell, AE and Matthews, E and Miller, MJ and Unger, ER and Bertolli, J and Hinckley, A and Lin, JS and Scott, JD and Struminger, BB and Ramers, C}, title = {A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.}, journal = {Trials}, volume = {24}, number = {1}, pages = {524}, pmid = {37573421}, issn = {1745-6215}, support = {75D30121C11341/CC/CDC HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; Prospective Studies ; Muscle Fatigue ; Quality Improvement ; Single-Blind Method ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions.

METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts.

DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.}, } @article {pmid37573078, year = {2023}, author = {Iftekhar, N and Sivan, M}, title = {Venous insufficiency and acrocyanosis in long COVID: dysautonomia.}, journal = {Lancet (London, England)}, volume = {402}, number = {10401}, pages = {e9}, doi = {10.1016/S0140-6736(23)01461-7}, pmid = {37573078}, issn = {1474-547X}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Venous Insufficiency ; *Primary Dysautonomias/diagnosis/etiology ; }, } @article {pmid37569899, year = {2023}, author = {Bouillet, L and Deroux, A and Benmarce, M and Guérin, C and Bouvet, L and Garnier, O and Martin, DK and Vilgrain, I}, title = {Molecular Mechanisms of Endothelialitis in SARS-CoV-2 Infection: Evidence for VE-Cadherin Cleavage by ACE2.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569899}, issn = {1422-0067}, mesh = {Humans ; *Endothelial Cells/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; *COVID-19/metabolism ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/metabolism ; Cadherins/metabolism ; Endothelium, Vascular/metabolism ; }, abstract = {Long COVID-19 syndrome appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damage to microcapillaries, microthrombi, and endothelialitis. However, the mechanisms involved in these processes remain to be elucidated. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium, which provides a the major function is to prevent coagulation. A component of endothelial cell junctions is VE-cadherin, which is responsible for maintaining the integrity of the vessels through homophilic interactions of its Ca[++]-dependent adhesive extracellular domain. Here we provide the first evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the positions [256]P-F[257] and [321]PMKP-[325]L. Indeed, incubation of hrVE-ED with the active ectopeptidase hrACE2 for 16 hrs in the presence of 10 μM ZnCl2 showed a dose-dependent (from 0.2 ng/μL to 2 ng/μL) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19 we detected a circulating form of ACE2 with an apparent molecular mass of 70 kDa, which was barely detectable in patients with mild COVID-19. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 to cleave VE-cadherin, which leads to potential biomarkers of SARS-CoV-2 infection related with the vascular disease in "Long COVID-19".}, } @article {pmid37569612, year = {2023}, author = {Kubiak, JZ and Kloc, M}, title = {Coronavirus Disease Pathophysiology: Biomarkers, Potential New Remedies, Comorbidities, Long COVID-19, Post Pandemic Epidemiological Surveillance.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569612}, issn = {1422-0067}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Biomarkers ; }, abstract = {The toughest challenge modern biomedical research ever faced was the rapid understanding of the SARS-CoV-2 physiopathology [...].}, } @article {pmid37569053, year = {2023}, author = {Colas, C and Le Berre, Y and Fanget, M and Savall, A and Killian, M and Goujon, I and Labeix, P and Bayle, M and Féasson, L and Roche, F and Hupin, D}, title = {Physical Activity in Long COVID: A Comparative Study of Exercise Rehabilitation Benefits in Patients with Long COVID, Coronary Artery Disease and Fibromyalgia.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {15}, pages = {}, pmid = {37569053}, issn = {1660-4601}, mesh = {Humans ; *Coronary Artery Disease ; Post-Acute COVID-19 Syndrome ; *Fibromyalgia ; Hand Strength ; *COVID-19 ; Exercise Therapy ; Exercise ; Exercise Test ; }, abstract = {Exercise in long COVID is poorly studied. Nevertheless, exerciserehabilitation could improve cardiorespiratory, muscular and autonomic functions. We aimed to investigate improvement in physical and autonomic performances of long COVID patients (n = 38) after a 4-week exercise rehabilitation program (3 sessions/week) compared to two control groups composed of coronary artery disease (n = 38) and fibromyalgia patients (n = 38), two populations for whom exercise benefits are well known. Efficacy of exercise training was assessed by a cardiopulmonary exercise test, a handgrip force test, and a supine heart rate variability recording at rest before and after the rehabilitation program. Cardiorespiratory and muscular parameters were enhanced after exercise rehabilitation in the three groups (p < 0.001). No significant difference was observed for the autonomic variables. Through this comparative study with control groups, we confirm and reinforce the interest of caring for long COVID patients without post-exertional symptom exacerbation by exercise rehabilitation of both strength and endurance training, by personalizing the program to the patient and symptoms.}, } @article {pmid37569003, year = {2023}, author = {Krysa, JA and Horlick, S and Pohar Manhas, K and Kovacs Burns, K and Buell, M and Santana, MJ and Russell, K and Papathanassoglou, E and Ho, C}, title = {Accessing Care Services for Long COVID Sufferers in Alberta, Canada: A Random, Cross-Sectional Survey Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {15}, pages = {}, pmid = {37569003}, issn = {1660-4601}, support = {RES0054905//CIHR/Canada ; }, mesh = {Adult ; Humans ; Alberta/epidemiology ; Canada ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Surveys and Questionnaires ; }, abstract = {Designing appropriate rehabilitation programs for long COVID-19 remains challenging. The purpose of this study was to explore the patient experience of accessing long COVID-19 rehabilitation and recovery services. In this cross-sectional, observational study, a telephone survey was administered to a random sample of persons with long COVID-19 in a Canadian province. Participants included adults who tested positive for COVID-19 between March and October 2021. Survey respondents (n = 330) included individuals who had been previously hospitalized for COVID-19 (n = 165) and those who had not been hospitalized ('non-hospitalized') for COVID-19 (n = 165). Significantly more previously hospitalized respondents visited a family doctor for long COVID-19 symptoms compared to non-hospitalized respondents (hospitalized: n = 109 (66.1%); non-hospitalized: n = 25 (15.2%); (p < 0.0001)). Previously hospitalized respondents reported significantly more referrals to specialty healthcare providers for long COVID-19 sym`ptoms (hospitalized: n = 45 (27.3%); non-hospitalized: n = 6 (3.6%); (p < 0.001)). A comparable number of respondents in both groups accessed care services that did not require a referral to manage their long COVID-19 symptoms (hospitalized: n = 31 (18.8%); non-hospitalized: n = 20 (12.1%); (p = 0.20)). These findings demonstrate the diversity of recovery services used by individuals with long COVID-19 and emphasize the need for multidisciplinary long COVID-19 rehabilitation and recovery care pathways.}, } @article {pmid37568896, year = {2023}, author = {Vasilev, Y and Blokhin, I and Khoruzhaya, A and Kodenko, M and Kolyshenkov, V and Nanova, O and Shumskaya, Y and Omelyanskaya, O and Vladzymyrskyy, A and Reshetnikov, R}, title = {Routine Brain MRI Findings on the Long-Term Effects of COVID-19: A Scoping Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {15}, pages = {}, pmid = {37568896}, issn = {2075-4418}, support = {122112400040-1//Reference datasets for sustainable development of artificial intelligence-based diagnostics to minimize the long-term impact of the COVID-19 pandemic on the health of the Moscow population/ ; }, abstract = {RATIONALE AND OBJECTIVES: Post-COVID condition (PCC) is associated with long-term neuropsychiatric symptoms. Magnetic resonance imaging (MRI) in PCC examines the brain metabolism, connectivity, and morphometry. Such techniques are not easily available in routine practice. We conducted a scoping review to determine what is known about the routine MRI findings in PCC patients.

MATERIALS AND METHODS: The PubMed database was searched up to 11 April 2023. We included cohort, cross-sectional, and before-after studies in English. Articles with only advanced MRI sequences (DTI, fMRI, VBM, PWI, ASL), preprints, and case reports were excluded. The National Heart, Lung, and Blood Institute and PRISMA Extension tools were used for quality assurance.

RESULTS: A total of 7 citations out of 167 were included. The total sample size was 451 patients (average age 51 ± 8 years; 67% female). Five studies followed a single recovering cohort, while two studies compared findings between two severity groups. The MRI findings were perivascular spaces (47%), microbleeds (27%) and white matter lesions (10%). All the studies agreed that PCC manifestations are not associated with specific MRI findings.

CONCLUSION: The results of the included studies are heterogeneous due to the low agreement on the types of MRI abnormalities in PCC. Our findings indicate that the routine brain MRI protocol has little value for long COVID diagnostics.}, } @article {pmid37568393, year = {2023}, author = {Błażejewski, G and Witkoś, J}, title = {The Impact of COVID-19 on Menstrual Cycle in Women.}, journal = {Journal of clinical medicine}, volume = {12}, number = {15}, pages = {}, pmid = {37568393}, issn = {2077-0383}, abstract = {BACKGROUND: The COVID-19 pandemic has become the largest and most diverse to threaten the health of humanity since the 1918 influenza pandemic.

METHODS: This study involved 113 women who had suffered from COVID-19. The study was conducted as interviews with each woman during visits to a clinic prior to the start of their post-COVID-19 physiotherapy treatment cycle. The aim of this study was to assess the prevalence of changes in the women's monthly cycles related to COVID-19, as well as to analyse correlations between dependent variables relating to changes in the monthly cycle and independent variables relating to other factors, such as age, weight, number and type of vaccinations, and time since illness. Additionally, the study assesses correlations between the monthly cycle and COVID-19 symptoms persisting after the illness (long COVID).

RESULTS: Women who reported more symptoms of COVID-19 were more likely to report changes in their menstrual cycle occurring after the SARS-CoV-2 infection, compared with women whose disease course was mild. Women who declared that COVID-19 affected their monthly cycles most often indicated increases in abdominal, lower abdominal, and joint and muscle pain, as well as in the severity of headaches during monthly bleeding. A small percentage of women indicated that their monthly cycles were longer and their regularity disrupted.

CONCLUSIONS: This study shows that the more COVID-19 symptoms a woman had, the more often there were noted changes in monthly cycle. The same relationship was also found for persistent long COVID symptoms. The longer the time lapse since the COVID-19 infection, the less frequently changes in the monthly cycle were recorded.}, } @article {pmid37567939, year = {2023}, author = {Ishikura, T and Nakano, T and Kitano, T and Tokuda, T and Sumi-Akamaru, H and Naka, T}, title = {Serum ferritin level during hospitalization is associated with Brain Fog after COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13095}, pmid = {37567939}, issn = {2045-2322}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Hospitalization ; Mental Fatigue ; Ferritins ; Brain ; }, abstract = {The coronavirus disease 2019 (COVID-19) remains an epidemic worldwide. Most patients suffer residual symptoms, the so-called "Long COVID," which includes respiratory and neuropsychiatric symptoms. Brain Fog, one of the symptoms of Long COVID, is a major public health issue because it can impair patients' quality of life even after recovery from the disease. However, neither the pathogenesis nor the treatment of this condition remains unknown. We focused on serum ferritin levels in this study and collected information on the onset of Brain Fog through questionnaires and found that high ferritin levels during hospitalization were associated with the occurrence of Brain Fog. In addition, we excluded confounders as far as possible using propensity score analyses and found that ferritin was independently associated with Brain Fog in most of the models. We conducted phase analysis and evaluated the interaction of each phase with ferritin levels and Brain Fog. We found a positive correlation between serum ferritin levels during hospitalization and Brain Fog after COVID-19. High ferritin levels in patients with Brain Fog may reflect the contribution of chronic inflammation in the development of Brain Fog. This study provides a novel insight into the pathogenic mechanism of Brain Fog after COVID-19.}, } @article {pmid37567514, year = {2023}, author = {Assaf, S and Stenberg, H and Jesenak, M and Tarasevych, SP and Hanania, NA and Diamant, Z}, title = {Asthma in the era of COVID-19.}, journal = {Respiratory medicine}, volume = {218}, number = {}, pages = {107373}, doi = {10.1016/j.rmed.2023.107373}, pmid = {37567514}, issn = {1532-3064}, mesh = {Humans ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; *Asthma/diagnosis ; Comorbidity ; Adrenal Cortex Hormones/therapeutic use ; }, abstract = {Since its global invasion in 2019, COVID-19 has affected several aspects of patients' lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.}, } @article {pmid37567082, year = {2023}, author = {Al-Hakeim, HK and Abed, AK and Almulla, AF and Rouf Moustafa, S and Maes, M}, title = {Anxiety due to Long COVID is partially driven by activation of the tryptophan catabolite (TRYCAT) pathway.}, journal = {Asian journal of psychiatry}, volume = {88}, number = {}, pages = {103723}, doi = {10.1016/j.ajp.2023.103723}, pmid = {37567082}, issn = {1876-2026}, mesh = {Humans ; *Tryptophan/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Kynurenine ; Anxiety ; }, abstract = {This study examines whether activation of the tryptophan catabolite (TRYCAT) pathway is associated with anxiety symptoms due to Long COVID. We selected 90 participants, 60 Long COVID patients and 30 individuals without any symptoms following acute COVID-19 infection. Using cluster analysis and the Hamilton Anxiety Rating scale (HAMA) score, the pure HAMA anxiety score, serum tryptophan (TRP) and kynurenine (KYN), the KYN/TRP ratio (all measured during Long COVID), and oxygen saturation (SpO2) (measured during the acute phase of COVID-19), we were able to classify Long COVID patients into two distinct clusters with an adequate silhouette cohesion and separation index (0.58): cluster 1 (n = 61) and cluster 2 (n = 29). Cluster 2 patients had lower SpO2 and TRP levels, as well as higher KYN, KYN/TRP ratio, and HAMA scores than cluster 1. Regression analysis revealed that the KYN/TRP ratio explained 14.4 % of the variance in the HAMA score (F = 14.81, df = 1/88, p = 0.001). In addition, regression analysis revealed that SpO2 partially explained the variance in serum TRP (r = 0.396, p = 0.005), KYN/TRP ratio (r = - 0.248, p = 0.018), and the HAMA score (r = - 0.279, p = 0.008). The current data imply that decreased SpO2 during the acute phase of COVID-19 infection is predictive of anxiety caused by Long COVID. Our data reveal that around 32 % of Long COVID patients have elevated IDO activity in association with elevated anxiety.}, } @article {pmid37566973, year = {2023}, author = {Chen, KY and Lin, CK and Chen, NH}, title = {Effects of vitamin D and zinc deficiency in acute and long COVID syndrome.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {80}, number = {}, pages = {127278}, doi = {10.1016/j.jtemb.2023.127278}, pmid = {37566973}, issn = {1878-3252}, mesh = {Humans ; Vitamin D ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; SARS-CoV-2 ; *COVID-19 ; Vitamins ; *Vitamin D Deficiency/complications/therapy ; Minerals ; Zinc ; }, abstract = {OBJECTIVES: Acute inflammatory or neuropsychiatric symptoms, such as headache, fatigue, anosmia, and hyposmia, sometimes persist for more than 30 days or longer than 12 weeks after infection with the Omicron variant of SARS‑CoV‑2 (hereafter referred to as COVID-19). The aim of this study was to determine whether detection of zinc concentration or vitamin D concentration could provide treatment benefits for patients with COVID-19, thus reducing the risk of them experiencing long COVID.

METHODS: The interval between the date of COVID-19 diagnosis and the date of visit to pulmonary department for prolonged symptoms of COVID-19 was recorded for statistical analysis. Inductively coupled plasma mass spectrometry for detecting zinc and chemiluminescence immunoassay for detecting vitamin D were performed in laboratory tests.

RESULTS: Fifty-five patients were included. Of the participants, 29.1 % and 27.3 % had vitamin D and zinc deficiency, respectively. On average, the patients underwent long COVID treatment for 31.7 ± 17.7 days. A positive statistical correlation was observed between vitamin D and zinc concentrations (Pearson's correlation = 0.378). Compared with sufficient zinc levels, zinc deficiency was associated with a higher fibrinogen level (p < 0.05). Within 30 days, the observed vitamin D deficiency rate was only 21.4 %; after 30 days, the vitamin D deficiency rate rose to 37.0 % (McNemar's chi-square test; p < 0.05).

CONCLUSION: Zinc deficiency correlates to acute and persistent inflammation and vitamin D deficiency is associated with delayed recovery in long COVID syndrome.}, } @article {pmid37565330, year = {2023}, author = {Larson, JL and Zhou, W and Veliz, PT and Smith, S}, title = {Symptom Clusters in Adults with Post-COVID-19: A Cross-Sectional Survey.}, journal = {Clinical nursing research}, volume = {32}, number = {8}, pages = {1071-1080}, doi = {10.1177/10547738231191655}, pmid = {37565330}, issn = {1552-3799}, mesh = {Humans ; Adult ; *COVID-19 ; Cross-Sectional Studies ; Syndrome ; Mental Health ; }, abstract = {More than 100 symptoms have been reported for post-coronavirus disease 2019 (COVID-19) and this study aimed to organize self-reported symptoms by identifying symptom clusters. We used a cross-sectional survey with a convenience sample of 491 adults who reported experiencing prolonged symptoms of COVID. A list of 25 symptoms of post-COVID-19 was used to measure the symptoms, and exploratory factor analysis was undertaken to identify symptom clusters for people with symptoms lasting 5 to 8 weeks and 9 weeks or longer. Six symptom clusters were identified for each of the two groups, and five clusters were similar across both groups: respiratory, general viral, smell/taste, cognitive cardiac, and mental health. The >9-week group reported symptoms primarily from two factors: respiratory-muscular and mental health. Post-COVID-19 symptom clusters differ across timeframes. Symptom clusters were useful in establishing coherent patterns of multiple complex symptoms.}, } @article {pmid37565145, year = {2023}, author = {Lechuga, GC and Morel, CM and De-Simone, SG}, title = {Hematological alterations associated with long COVID-19.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1203472}, pmid = {37565145}, issn = {1664-042X}, abstract = {Long COVID-19 is a condition characterized by persistent symptoms lasting beyond the acute phase of COVID-19. Long COVID-19 produces diverse symptomatology and can impact organs and systems, including the hematological system. Several studies have reported, in COVID-19 patients, hematological abnormalities. Most of these alterations are associated with a higher risk of severe disease and poor outcomes. This literature review identified studies reporting hematological parameters in individuals with Long COVID-19. Findings suggest that Long COVID-19 is associated with a range of sustained hematological alterations, including alterations in red blood cells, anemia, lymphopenia, and elevated levels of inflammatory markers such as ferritin, D-dimer, and IL-6. These alterations may contribute to a better understanding of the pathophysiology of Long COVID-19 and its associated symptoms. However, further research is needed to elucidate the underlying mechanisms and potential treatments for these hematological changes in individuals with Long COVID-19.}, } @article {pmid37564427, year = {2023}, author = {Soriano-Arandes, A and Brett, A and Buonsenso, D and Emilsson, L and de la Fuente Garcia, I and Gkentzi, D and Helve, O and Kepp, KP and Mossberg, M and Muka, T and Munro, A and Papan, C and Perramon-Malavez, A and Schaltz-Buchholzer, F and Smeesters, PR and Zimmermann, P}, title = {Policies on children and schools during the SARS-CoV-2 pandemic in Western Europe.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1175444}, pmid = {37564427}, issn = {2296-2565}, mesh = {*SARS-CoV-2 ; Europe/epidemiology ; Pandemics ; Systemic Inflammatory Response Syndrome ; Child ; *COVID-19/epidemiology/complications ; Humans ; Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {During the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mitigation policies for children have been a topic of considerable uncertainty and debate. Although some children have co-morbidities which increase their risk for severe coronavirus disease (COVID-19), and complications such as multisystem inflammatory syndrome and long COVID, most children only get mild COVID-19. On the other hand, consistent evidence shows that mass mitigation measures had enormous adverse impacts on children. A central question can thus be posed: What amount of mitigation should children bear, in response to a disease that is disproportionally affecting older people? In this review, we analyze the distinct child versus adult epidemiology, policies, mitigation trade-offs and outcomes in children in Western Europe. The highly heterogenous European policies applied to children compared to adults did not lead to significant measurable differences in outcomes. Remarkably, the relative epidemiological importance of transmission from school-age children to other age groups remains uncertain, with current evidence suggesting that schools often follow, rather than lead, community transmission. Important learning points for future pandemics are summarized.}, } @article {pmid37562815, year = {2023}, author = {Sivan, M and Lawrence, RR and Francis, E}, title = {Digital interactive patient reported outcome measures for long term conditions.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1816}, doi = {10.1136/bmj.p1816}, pmid = {37562815}, issn = {1756-1833}, mesh = {Humans ; *Patient Reported Outcome Measures ; }, } @article {pmid37561683, year = {2023}, author = {Lorman, V and Razzaghi, H and Song, X and Morse, K and Utidjian, L and Allen, AJ and Rao, S and Rogerson, C and Bennett, TD and Morizono, H and Eckrich, D and Jhaveri, R and Huang, Y and Ranade, D and Pajor, N and Lee, GM and Forrest, CB and Bailey, LC}, title = {A machine learning-based phenotype for long COVID in children: An EHR-based study from the RECOVER program.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0289774}, pmid = {37561683}, issn = {1932-6203}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {*Post-Acute COVID-19 Syndrome ; Disease Progression ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Machine Learning ; Phenotype ; Humans ; *COVID-19/diagnosis/complications ; }, abstract = {As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS- CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses.}, } @article {pmid37561665, year = {2023}, author = {Ford, ND and Slaughter, D and Edwards, D and Dalton, A and Perrine, C and Vahratian, A and Saydah, S}, title = {Long COVID and Significant Activity Limitation Among Adults, by Age - United States, June 1-13, 2022, to June 7-19, 2023.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {72}, number = {32}, pages = {866-870}, pmid = {37561665}, issn = {1545-861X}, mesh = {Adolescent ; Adult ; Humans ; Middle Aged ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Population Surveillance ; *Post-Acute COVID-19 Syndrome/epidemiology ; Prevalence ; United States/epidemiology ; }, abstract = {Long COVID is a condition encompassing a wide range of health problems that emerge, persist, or return following COVID-19. CDC analyzed national repeat cross-sectional Household Pulse Survey data to estimate the prevalence of long COVID and significant related activity limitation among U.S. adults aged ≥18 years by age group. Data from surveys completed between June 1-13, 2022, and June 7-19, 2023, indicated that long COVID prevalence decreased from 7.5% (95% CI = 7.1-7.9) to 6.0% (95% CI = 5.7-6.3) among the overall U.S. adult population, irrespective of history of previous COVID-19, and from 18.9% (95% CI = 17.9-19.8) to 11.0% (95% CI = 10.4-11.6) among U.S. adults reporting previous COVID-19. Among both groups, prevalence decreased from June 1-13, 2022, through January 4-16, 2023, before stabilizing. When stratified by age, only adults aged <60 years experienced significant rates of decline (p<0.01). Among adults reporting previous COVID-19, prevalence decreased among those aged 30-79 years through fall or winter and then stabilized. During June 7-19, 2023, 26.4% (95% CI = 24.0-28.9) of adults with long COVID reported significant activity limitation, the prevalence of which did not change over time. These findings help guide the ongoing COVID-19 prevention efforts and planning for long COVID symptom management and future health care service needs.}, } @article {pmid37561435, year = {2024}, author = {Saltzman, LY and Longo, M and Hansel, TC}, title = {Long-COVID stress symptoms: Mental health, anxiety, depression, or posttraumatic stress.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {16}, number = {7}, pages = {1169-1178}, doi = {10.1037/tra0001567}, pmid = {37561435}, issn = {1942-969X}, mesh = {Humans ; Anxiety/psychology/etiology ; *Depression/etiology/psychology ; *Post-Acute COVID-19 Syndrome/complications/diagnosis/psychology ; *Stress Disorders, Post-Traumatic/etiology/psychology/therapy ; }, abstract = {OBJECTIVE: Currently, there is no single profile of mental health sequela in long-coronavirus disease (COVID) patients, impacting identification, treatment, and exacerbating stigma among this population. This article highlights the rationale for mental health professionals to consider a summary of mental health symptoms in long-COVID patients.

METHOD: This article provides an overview of the existing literature regarding the health and mental health impact of long COVID on patients and proposes an approach to conceptualizing mental health symptoms in individuals living with long COVID. This article summarizes the health and mental health impacts of long COVID and underscores the limitations of the current approach to measuring and screening mental health symptoms in long-COVID patients.

RESULTS: Long-COVID patients have reported new and worsening mental health symptoms; most frequently reported are depression, anxiety, posttraumatic stress disorder (PTSD), and insomnia. The article concludes by proposing the notion of long-COVID stress symptoms and calls for mental health researchers to identify the unique and complex mental health profiles emerging among this patient population.

CONCLUSIONS: Though some long-COVID patients survived life-threatening illnesses and may, therefore, meet the formal criteria for PTSD, many will present with posttraumatic symptomology that mimics PTSD but may not arise from life-threatening medical trauma. A better understanding of the mental health burden of long-COVID stress symptoms is essential to providing efficient and effective mental health treatment, supporting physicians treating long-COVID patients, and enhancing access to and utilization of medical services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid37561027, year = {2023}, author = {Rouphael, NG and Branche, AR and Diemert, DJ and Falsey, AR and Losada, C and Baden, LR and Frey, SE and Whitaker, JA and Little, SJ and Kamidani, S and Walter, EB and Novak, RM and Rupp, R and Jackson, LA and Babu, TM and Kottkamp, AC and Luetkemeyer, AF and Immergluck, LC and Presti, RM and Bäcker, M and Winokur, PL and Mahgoub, SM and Goepfert, PA and Fusco, DN and Atmar, RL and Posavad, CM and Netzl, A and Smith, DJ and Telu, K and Mu, J and McQuarrie, LJ and Makowski, M and Makhene, MK and Crandon, S and Montefiori, DC and Roberts, PC and Beigel, JH and , }, title = {Immunogenicity of a 2-Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {12}, pages = {1662-1666}, pmid = {37561027}, issn = {1537-6613}, support = {UM1 AI148450/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; 75N93021C00012/AI/NIAID NIH HHS/United States ; UM1 AI148685/AI/NIAID NIH HHS/United States ; R01 AI165818/AI/NIAID NIH HHS/United States ; C0000008/CL/CLC NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; /HH/HHS/United States ; UM1 AI148575/AI/NIAID NIH HHS/United States ; UM1 AI148576/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Humans ; Vaccines, Combined ; *2019-nCoV Vaccine mRNA-1273 ; Clinical Protocols ; RNA, Messenger/genetics ; }, abstract = {We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.}, } @article {pmid37559726, year = {2023}, author = {Kervevan, J and Staropoli, I and Slama, D and Jeger-Madiot, R and Donnadieu, F and Planas, D and Pietri, MP and Loghmari-Bouchneb, W and Alaba Tanah, M and Robinot, R and Boufassa, F and White, M and Salmon-Ceron, D and Chakrabarti, LA}, title = {Divergent adaptive immune responses define two types of long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1221961}, pmid = {37559726}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Vaccines ; SARS-CoV-2 ; Antibodies, Viral ; Antiviral Agents ; Immunoglobulin G ; }, abstract = {BACKGROUND: The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination.

METHODS: Long COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29).

RESULTS: The spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups. Multiplexed antibody analyses to 30 different viral antigens showed that LC- patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC- patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC- group.

CONCLUSIONS: These findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID.}, } @article {pmid37559387, year = {2023}, author = {Brogna, C and Viduto, V and Fabrowski, M and Cristoni, S and Marino, G and Montano, L and Piscopo, M}, title = {The importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2244718}, pmid = {37559387}, issn = {1949-0984}, mesh = {Humans ; SARS-CoV-2 ; *Gastrointestinal Microbiome ; *COVID-19 ; }, abstract = {Zhou et al. study nicely traces a significant topic in COVID-19 infection: the persistence of the virus within the intestinal tract. Many pathological mechanisms have been noted in the current literature about the mode of infection and propagation of SARS-CoV-2 in the human body. Nevertheless, there are still many concerns about this: only some things seem well understood. We present a different point of view by illustrating the importance of the gut microbiome in the pathogenesis of COVID-19 disorders.}, } @article {pmid37555926, year = {2023}, author = {Lam, GY and Damant, RW and Ferrara, G and Lim, RK and Stickland, MK and Ogando, NS and Power, C and Smith, MP}, title = {Characterizing long-COVID brain fog: a retrospective cohort study.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4640-4646}, pmid = {37555926}, issn = {1432-1459}, mesh = {Humans ; Female ; *Quality of Life ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; *COVID-19/complications ; Brain ; }, abstract = {BACKGROUND: Long COVID or post-COVID condition (PCC) is a common complication following acute COVID-19 infection. PCC is a multi-systems disease with neurocognitive impairment frequently reported regardless of age. Little is known about the risk factors, associated biomarkers and clinical trajectory of patients with this symptom.

OBJECTIVE: To determine differences in clinical risk factors, associated biochemical markers and longitudinal clinical trajectories between patients with PCC with subjective neurocognitive symptoms (NC+) or without (NC-).

METHODS: A retrospective longitudinal cohort study was performed using a well-characterized provincial database of patients with clinically confirmed PCC separated into NC+ and NC- cohorts. Demographical, clinical and biochemical differences at initial consultation between the two patient cohorts were analyzed in cross-section. Multivariate regression analyses were conducted to identify independent risk factors for neurocognitive impairment. Determination of the recovery trajectory was performed using serial assessments of the patient-reported health-related quality of life (HR-QoL) metric Eq-5D-5L-vas score.

FINDINGS: Women, milder acute infection and pre-existing mental health diagnoses were independently associated with subjective neurocognitive impairment at 8 months post-infection. NC + patients demonstrated lower levels of IgG, IgG1 and IgG3 compared to NC- patients. The NC + cohort had poorer HR-QoL at initial consultation 8 months post-infection with gradual improvement over 20 months post-infection.

CONCLUSIONS: Neurocognitive impairment represents a severe phenotype of PCC, associated with unique risk factors, aberrancy in immune response and a delayed recovery trajectory. Those with risk factors for neurocognitive impairment can be identified early in the disease trajectory for more intense medical follow-up.}, } @article {pmid37555900, year = {2023}, author = {Rabady, S and Hoffmann, K and Aigner, M and Altenberger, J and Brose, M and Costa, U and Denk-Linnert, DM and Gruber, S and Götzinger, F and Helbok, R and Hüfner, K and Koczulla, R and Kurz, K and Lamprecht, B and Leis, S and Löffler, J and Müller, CA and Rittmannsberger, H and Rommer, PS and Sator, P and Strenger, V and Struhal, W and Untersmayr, E and Vonbank, K and Wancata, J and Weber, T and Wendler, M and Zwick, RH}, title = {[S1 guidelines for the management of postviral conditions using the example of post-COVID-19].}, journal = {Wiener klinische Wochenschrift}, volume = {135}, number = {Suppl 4}, pages = {525-598}, pmid = {37555900}, issn = {1613-7671}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Medicine ; }, abstract = {These S1 guidelines are an updated and expanded version of the S1 guidelines on long COVID differential diagnostic and management strategies. They summarize the state of knowledge on postviral conditions like long/post COVID at the time of writing. Due to the dynamic nature of knowledge development, they are intended to be "living guidelines". The focus is on practical applicability at the level of primary care, which is understood to be the appropriate place for initial access and for primary care and treatment. The guidelines provide recommendations on the course of treatment, differential diagnostics of the most common symptoms that can result from infections like with SARS-CoV-2, treatment options, patient management and care, reintegration and rehabilitation. The guidelines have been developed through an interdisciplinary and interprofessional process and provide recommendations on interfaces and possibilities for collaboration.}, } @article {pmid37554293, year = {2023}, author = {Sousa, RAL and Yehia, A and Abulseoud, OA}, title = {Attenuation of ferroptosis as a potential therapeutic target for neuropsychiatric manifestations of post-COVID syndrome.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1237153}, pmid = {37554293}, issn = {1662-4548}, abstract = {Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), is associated with the persistence of pre-existing or the emergence of new neurological and psychiatric manifestations as a part of a multi-system affection known collectively as "post-COVID syndrome." Cognitive decline is the most prominent feature among these manifestations. The underlying neurobiological mechanisms remain under intense investigation. Ferroptosis is a form of cell death that results from the excessive accumulation of intracellular reactive iron, which mediates lipid peroxidation. The accumulation of lipid-based reactive oxygen species (ROS) and the impairment of glutathione peroxidase 4 (GPX4) activity trigger ferroptosis. The COVID-19-associated cytokine storm enhances the levels of circulating pro-inflammatory cytokines and causes immune-cell hyper-activation that is tightly linked to iron dysregulation. Severe COVID-19 presents with iron overload as one of the main features of its pathogenesis. Iron overload promotes a state of inflammation and immune dysfunction. This is well demonstrated by the strong association between COVID-19 severity and high levels of ferritin, which is a well-known inflammatory and iron overload biomarker. The dysregulation of iron, the high levels of lipid peroxidation biomarkers, and the inactivation of GPX4 in COVID-19 patients make a strong case for ferroptosis as a potential mechanism behind post-COVID neuropsychiatric deficits. Therefore, here we review the characteristics of iron and the attenuation of ferroptosis as a potential therapeutic target for neuropsychiatric post-COVID syndrome.}, } @article {pmid37553613, year = {2023}, author = {Li, R and Liu, G and Zhang, X and Zhang, M and Lu, J and Li, H}, title = {Altered intrinsic brain activity and functional connectivity in COVID-19 hospitalized patients at 6-month follow-up.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {521}, pmid = {37553613}, issn = {1471-2334}, support = {82202118//National Natural Science Foundation of China/ ; 82271963//National Natural Science Foundation of China/ ; HZ2021ZCLJ005//Huizhi Ascent Project of Xuanwu Hospital/ ; L222097//Natural Science Foundation of Beijing Municipality/ ; }, mesh = {Humans ; *Brain Mapping/methods ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; *COVID-19/diagnostic imaging ; SARS-CoV-2 ; Brain/diagnostic imaging ; Magnetic Resonance Imaging/methods ; }, abstract = {BACKGROUND: Although most patients can recover from SARS-CoV-2 infection during the short-term, the long-term effects of COVID-19 on the brain remain explored. Functional MRI (fMRI) could potentially elucidate or otherwise contribute to the investigation of the long COVID syndrome. A lower fMRI response would be translated into decreased brain activity or delayed signal transferring reflecting decreased connectivity. This research aimed to investigate the long-term alterations in the local (regional) brain activity and remote (interregional) functional connection in recovered COVID-19.

METHODS: Thirty-five previously hospitalized COVID-19 patients underwent 3D T1weighed imaging and resting-state fMRI at 6-month follow-up, and 36 demographic-matched healthy controls (HCs) were recruited accordingly. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Spearman correlation analyses were performed to evaluate the association between brain function changes and clinical variables.

RESULTS: The incidence of neurosymptoms (6/35, 17.14%) decreased significantly at 6-month follow-up, compared with COVID-19 hospitalization stage (21/35, 60%). Compared with HCs, recovered COVID-19 exhibited higher ALFF in right precuneus, middle temporal gyrus, middle and inferior occipital gyrus, lower ALFF in right middle frontal gyrus and bilateral inferior temporal gyrus. Furthermore, setting seven abnormal activity regions as seeds, we found increased FC between right middle occipital gyrus and left inferior occipital gyrus, and reduced FC between right inferior occipital gyrus and right inferior temporal gyrus/bilateral fusiform gyrus, and between right middle frontal gyrus and right middle frontal gyrus/ supplementary motor cortex/ precuneus. Additionally, abnormal ALFF and FC were associated with clinical variables.

CONCLUSIONS: COVID-19 related neurological symptoms can self heal over time. Recovered COVID-19 presented functional alterations in right frontal, temporal and occipital lobe at 6-month follow-up. Most regional disturbances in ALFF were related to the weakening of short-range regional interactions in the same brain function.}, } @article {pmid37553189, year = {2023}, author = {Mansoubi, M and Dawes, J and Bhatia, A and Vashisht, H and Collett, J and Greenwood, DC and Ezekiel, L and O'Connor, D and Leveridge, P and Rayner, C and Read, F and Sivan, M and Tuckerbell, I and Ward, T and Delaney, B and Muhlhausen, W and , and Dawes, H}, title = {Digital home monitoring for capturing daily fluctuation of symptoms; a longitudinal repeated measures study: Long Covid Multi-disciplinary Consortium to Optimise Treatments and Services across the NHS (a LOCOMOTION study).}, journal = {BMJ open}, volume = {13}, number = {8}, pages = {e071428}, pmid = {37553189}, issn = {2044-6055}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19/therapy ; State Medicine ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Research Design ; }, abstract = {INTRODUCTION: A substantial proportion of COVID-19 survivors continue to have symptoms more than 3 months after infection, especially of those who required medical intervention. Lasting symptoms are wide-ranging, and presentation varies between individuals and fluctuates within an individual. Improved understanding of undulation in symptoms and triggers may improve efficacy of healthcare providers and enable individuals to better self-manage their Long Covid. We present a protocol where we aim to develop and examine the feasibility and usability of digital home monitoring for capturing daily fluctuation of symptoms in individuals with Long Covid and provide data to facilitate a personalised approach to the classification and management of Long Covid symptoms.

METHODS AND ANALYSIS: This study is a longitudinal prospective cohort study of adults with Long Covid accessing 10 National Health Service (NHS) rehabilitation services in the UK. We aim to recruit 400 people from participating NHS sites. At referral to study, 6 weeks and 12 weeks, participants will complete demographic data (referral to study) and clinical outcome measures, including ecological momentary assessment (EMA) using personal mobile devices. EMA items are adapted from the COVID-19 Yorkshire Rehabilitation Scale items and include self-reported activities, symptoms and psychological factors. Passive activity data will be collected through wrist-worn sensors. We will use latent class growth models to identify trajectories of experience, potential phenotypes defined by co-occurrence of symptoms and inter-relationships between stressors, symptoms and participation in daily activities. We anticipate that n=300 participants provide 80% power to detect a 20% improvement in fatigue over 12 weeks in one class of patients relative to another.

ETHICS AND DISSEMINATION: The study was approved by the Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Findings will be disseminated in peer-reviewed publications and presented at conferences.

TRIAL REGISTRATION NUMBER: ISRCTN15022307.}, } @article {pmid37553019, year = {2023}, author = {Rastogi, R and Cerda, IH and Ibrahim, A and Chen, JA and Stevens, C and Liu, CH}, title = {Long COVID and psychological distress in young adults: Potential protective effect of a prior mental health diagnosis.}, journal = {Journal of affective disorders}, volume = {340}, number = {}, pages = {639-648}, doi = {10.1016/j.jad.2023.08.031}, pmid = {37553019}, issn = {1573-2517}, support = {R01 MH129360/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Young Adult ; Adult ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Mental Health ; Disease Progression ; *Psychological Distress ; COVID-19 Testing ; }, abstract = {BACKGROUND: Although young adulthood is a period characterized by marked psychological vulnerability, young adults are typically considered to be in good physical health and are therefore understudied with respect to the effects of COVID-19 infection and long COVID. The present study examined associations between post-acute sequelae of COVID-19 (PASC) and serious psychological distress during young adulthood, and tested whether prior mental health diagnosis moderated this association.

METHODS: Participants were 44,652 young adults who completed the Spring 2022 administration of the American College Health Association-National College Health Assessment III (ACHA-NCHA). Blockwise logistic regressions tested the odds of meeting the clinical threshold for serious psychological distress.

RESULTS: PASC was associated with 53 % increased likelihood of meeting the clinical threshold for serious psychological distress. Among young adults with a prior mental health diagnosis, PASC predicted 36 % increased odds of serious psychological distress; among those without a diagnosis, PASC predicted 81 % increased odds.

LIMITATIONS: PASC was assessed using a single self-report item rather than a clinical diagnosis of specific symptomatology. The analyses were cross-sectional and relied on concurrent reports of PASC and psychological distress which precluded us from making claims regarding directionality of the associations. The outcome of generalized psychological distress limited us from generating targeted treatment recommendations.

CONCLUSIONS: PASC may confer elevated psychological distress among young adults. The association of PASC to serious psychological distress was stronger in young adults without a mental health diagnosis than those with a diagnosis. Prior experience with mental illness may mitigate the psychological burden of long-term symptomatology.}, } @article {pmid37550861, year = {2023}, author = {Lee, J and Seo, GH and Song, K}, title = {Beyond Acute COVID-19: Investigating the Incidence of Subacute Thyroiditis in Long COVID-19 in Korea.}, journal = {Endocrinology and metabolism (Seoul, Korea)}, volume = {38}, number = {4}, pages = {455-461}, pmid = {37550861}, issn = {2093-5978}, mesh = {Male ; Humans ; Female ; Aged ; *Thyroiditis, Subacute/epidemiology/diagnosis ; *COVID-19/diagnosis/epidemiology ; Incidence ; COVID-19 Testing ; Republic of Korea/epidemiology ; }, abstract = {BACKGRUOUND: The correlation between acute coronavirus disease 2019 (COVID-19) and subacute thyroiditis (SAT) has not been clearly investigated in "long COVID" patients. We aimed to investigate the incidence of SAT during convalescence and after the acute phase of COVID-19, comparing with that of the general population.

METHODS: Data from a total of 422,779 COVID-19 patients and a control group of 2,113,895 individuals were analyzed. The index date was defined as the date 3 months after confirmation of COVID-19. The incidence rate (IR) of SAT and hazard ratios (HRs) were calculated per 100,000 persons. Subgroup analysis included analysis of HRs 90-179 and 180 days post-COVID-19 diagnosis; and additional analysis was conducted according to hospitalization status, sex, and age group.

RESULTS: The IR of SAT was 17.28 per 100,000 persons (95% confidence interval [CI], 12.56 to 23.20) in the COVID-19 group and 8.63 (95% CI, 6.37 to 11.45) in the control group. The HR of COVID-19 patients was 1.76 (95% CI, 1.01 to 3.06; P=0.045). The HR of SAT was 1.39 (95% CI, 0.82 to 2.34; P=0.220) up to 6 months after the index date and 2.30 (95% CI, 1.60 to 3.30; P<0.001) beyond 6 months. The HR for SAT among COVID-19 patients was 2.00 (95% CI, 1.41 to 2.83) in hospitalized patients and 1.76 (95% CI, 1.01 to 3.06) in non-hospitalized patients compared to the control group. The IR of SAT was 27.09 (95% CI, 20.04 to 35.82) for females and 6.47 (95% CI, 3.34 to 11.30) for males. In the 19 to 64 age group, the IR of SAT was 18.19 (95% CI, 13.70 to 23.67), while the IR was 9.18 (95% CI, 7.72 to 10.84) in the 65 to 69 age group.

CONCLUSION: SAT could be a potential long-term complication of COVID-19. Long-term surveillance for thyroid dysfunction is needed especially in hospitalized, female and young-aged subjects.}, } @article {pmid37549214, year = {2023}, author = {Torres, G and Constantinou, D and Gradidge, P and Patel, D and Patricios, J}, title = {Exercise is the Most Important Medicine for COVID-19.}, journal = {Current sports medicine reports}, volume = {22}, number = {8}, pages = {284-289}, pmid = {37549214}, issn = {1537-8918}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Exercise ; }, abstract = {COVID-19 infection and long COVID affect multiple organ systems, including the respiratory, cardiovascular, renal, digestive, neuroendocrine, musculoskeletal systems, and sensory organs. Exerkines, released during exercise, have a potent crosstalk effect between multiple body systems. This review describes the evidence of how exerkines can mitigate the effects of COVID-19 in each organ system that the virus affects. The evidence presented in the review suggests that exercise should be considered a first-line strategy in the prevention and treatment of COVID-19 infection and long COVID disease.}, } @article {pmid37549204, year = {2023}, author = {Cremonesi, M and Felicetta, A and Cannata, F and Serio, S and van Beek, JJP and Bombace, S and My, I and Zanon, V and Catalano, C and Papadopoulou, V and Monti, L and Chiarito, M and Stefanini, G and Panico, C and Francone, M and Lugli, E and Kallikourdis, M and Condorelli, G}, title = {Long COVID-19 Cardiac Complications Are Associated With Autoimmunity to Cardiac Self-Antigens Sufficient to Cause Cardiac Dysfunction.}, journal = {Circulation}, volume = {148}, number = {6}, pages = {504-507}, doi = {10.1161/CIRCULATIONAHA.122.062672}, pmid = {37549204}, issn = {1524-4539}, mesh = {Humans ; Autoimmunity ; Autoantigens ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Autoantibodies ; *Heart Diseases/etiology ; *Autoimmune Diseases/complications ; }, } @article {pmid37548112, year = {2024}, author = {Wild, JM and Gleeson, FV and Svenningsen, S and Grist, JT and Saunders, LC and Collier, GJ and Sharma, M and Tcherner, S and Mozaffaripour, A and Matheson, AM and Parraga, G}, title = {Review of Hyperpolarized Pulmonary Functional [129] Xe MR for Long-COVID.}, journal = {Journal of magnetic resonance imaging : JMRI}, volume = {59}, number = {4}, pages = {1120-1134}, doi = {10.1002/jmri.28940}, pmid = {37548112}, issn = {1522-2586}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/diagnostic imaging/complications ; *Magnetic Resonance Imaging/methods ; *Lung/diagnostic imaging ; *Xenon Isotopes ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pulmonary Gas Exchange ; }, abstract = {The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed [129] Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on [129] Xe MR gas-exchange and ventilation imaging. A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine's Medical Subject Headings and key words: post-COVID-19, MRI, [129] Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020-2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants. Key findings included: 1) [129] Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and [129] Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean [129] Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection. Pulmonary functional MRI using inhaled hyperpolarized [129] Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.}, } @article {pmid37547607, year = {2023}, author = {Honchar, O and Ashcheulova, T}, title = {Spontaneous physical functional recovery after hospitalization for COVID-19: insights from a 1 month follow-up and a model to predict poor trajectory.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1212678}, pmid = {37547607}, issn = {2296-858X}, abstract = {BACKGROUND: Long COVID syndrome has emerged as a new global healthcare challenge, with impaired physical performance being a prominent debilitating factor. Cardiopulmonary rehabilitation is a mainstay of management of symptomatic post-COVID patients, and optimization of candidate selection might allow for more effective use of available resources.

METHODS: In order to study the natural dynamics and to identify predictors of physical functional recovery following hospitalization for COVID-19, 6 min walk test was performed pre-discharge in 176 patients (40% hypertensive, 53% female, mean age 53.2 ± 13.5 years) with re-evaluation at 1 month.

RESULTS: Six min walk distance and the reached percent of predicted distance (6MWD%) were suboptimal at both visits-396 ± 71 m (68.7 ± 12.4%) pre-discharge and 466 ± 65 m (81.8 ± 13.6%) at 1 month. Associated changes included significant oxygen desaturation (2.9 ± 2.5 and 2.3 ± 2.2%, respectively) and insufficient increment of heart rate during the test (24.9 ± 17.5 and 28.2 ± 12.0 bpm) that resulted in low reached percent of individual maximum heart rate (61.1 ± 8.1 and 64.3 ± 8.2%). Automatic clusterization of the study cohort by the 6MWD% changes has allowed to identify the subgroup of patients with poor "low base-low increment" trajectory of spontaneous post-discharge recovery that were characterized by younger age (38.2 ± 11.0 vs. 54.9 ± 12.1, p < 0.001) but more extensive pulmonary involvement by CT (43.7 ± 8.8 vs. 29.6 ± 19.4%, p = 0.029) and higher peak ESR values (36.5 ± 9.7 vs. 25.6 ± 12.8, p < 0.001). Predictors of poor recovery in multivariate logistic regression analysis included age, peak ESR, eGFR, percentage of pulmonary involvement by CT, need for in-hospital oxygen supplementation, SpO2 and mMRC dyspnea score pre-discharge, and history of hypertension.

CONCLUSION: COVID-19 survivors were characterized by decreased physical performance pre-discharge as assessed by the 6 min walk test and did not completely restore their functional status after 1 month of spontaneous recovery, with signs of altered blood oxygenation and dysautonomia contributing to the observed changes. Patients with poor "low base-low increment" trajectory of post-discharge recovery were characterized by younger age but more extensive pulmonary involvement and higher peak ESR values. Poor post-discharge recovery in the study cohort was predictable by the means of machine learning-based classification model that used age, history of hypertension, need for oxygen supplementation, and ESR as inputs.}, } @article {pmid37547275, year = {2023}, author = {Lemogne, C and Pitron, V}, title = {Shedding light on the work burden of long COVID.}, journal = {The Lancet regional health. Europe}, volume = {31}, number = {}, pages = {100678}, pmid = {37547275}, issn = {2666-7762}, } @article {pmid37547250, year = {2023}, author = {Schieffer, E and Schieffer, B}, title = {Corrigendum: The rationale for the treatment of long-COVID esymptoms-a cardiologist's view.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1244340}, doi = {10.3389/fcvm.2023.1244340}, pmid = {37547250}, issn = {2297-055X}, abstract = {[This corrects the article DOI: 10.3389/fcvm.2022.992686.].}, } @article {pmid37545721, year = {2023}, author = {Comeau, D and Martin, M and Robichaud, GA and Chamard-Witkowski, L}, title = {Neurological manifestations of post-acute sequelae of COVID-19: which liquid biomarker should we use?.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1233192}, pmid = {37545721}, issn = {1664-2295}, abstract = {Long COVID syndrome, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent symptoms lasting 3-12 weeks post SARS-CoV-2 infection. Patients suffering from PASC can display a myriad of symptoms that greatly diminish quality of life, the most frequent being neuropsychiatric. Thus, there is an eminent need to diagnose and treat PASC related neuropsychiatric manifestation (neuro-PASC). Evidence suggests that liquid biomarkers could potentially be used in the diagnosis and monitoring of patients. Undoubtedly, such biomarkers would greatly benefit clinicians in the management of patients; however, it remains unclear if these can be reliably used in this context. In this mini review, we highlight promising liquid (blood and cerebrospinal fluid) biomarkers, namely, neuronal injury biomarkers NfL, GFAP, and tau proteins as well as neuroinflammatory biomarkers IL-6, IL-10, TNF-α, and CPR associated with neuro-PASC and discuss their limitations in clinical applicability.}, } @article {pmid37545414, year = {2023}, author = {Howe de la Torre, S and Parlatini, V and Cortese, S}, title = {Long-term central nervous system (CNS) consequences of COVID-19 in children.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {8}, pages = {703-720}, doi = {10.1080/14737175.2023.2239500}, pmid = {37545414}, issn = {1744-8360}, mesh = {Child ; Humans ; Adolescent ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Central Nervous System ; *Sleep Wake Disorders ; }, abstract = {INTRODUCTION: Neurological/neuropsychiatric symptoms are commonly reported by children/young people with long COVID, especially headache, fatigue, cognitive deficits, anosmia and ageusia, dizziness, mood symptoms, and sleep problems. However, reported prevalence estimates are highly variable due to study heterogeneity and often small sample size; most studies only considered short-term follow-ups; and, apart from mood and sleep problems, neuropsychiatric conditions have received less attention. Considering the potential debilitating effects of neurological/neuropsychiatric conditions, a comprehensive review of the topic is timely, and needed to support clinical recognition as well as to set the direction for future research.

AREAS COVERED: The authors discuss neurological/neuropsychiatric manifestations of long COVID in pediatric populations, with a focus on prevalence, associated demographic characteristics, and potential pathogenetic mechanisms.

EXPERT OPINION: Children/young people may develop persistent neurological/neuropsychiatric symptoms following acute SARS-CoV-2 infection, which may affect daily functioning and well-being. Studies in larger samples with longer follow-ups are needed to clarify prevalence and symptom duration; as well as less investigated risk factors, including genetic predisposition, ethnicity, and comorbidities. Controlled studies may help separate infection-related direct effects from pandemic-related psychosocial stressors. Clarifying pathogenetic mechanisms is paramount to develop more targeted and effective treatments; whilst screening programs and psychoeducation may enhance early recognition.}, } @article {pmid37545190, year = {2024}, author = {Hersche, R and Weise, A and Hummel, B and Barbero, M}, title = {Occupational therapy-based self-management education in persons with post-COVID-19 condition related fatigue: a feasibility study with a pre-post design.}, journal = {Disability and rehabilitation}, volume = {46}, number = {14}, pages = {3060-3066}, doi = {10.1080/09638288.2023.2242783}, pmid = {37545190}, issn = {1464-5165}, mesh = {Humans ; *COVID-19 ; Male ; *Feasibility Studies ; Female ; *Self-Management ; *Occupational Therapy/methods ; Middle Aged ; *Fatigue ; *SARS-CoV-2 ; Quality of Life ; Adult ; Pandemics ; Self Efficacy ; Aged ; Patient Education as Topic ; Activities of Daily Living ; Coronavirus Infections/rehabilitation ; Pneumonia, Viral/rehabilitation ; }, abstract = {PURPOSE: Persons with post-COVID condition are a growing population requiring support returning to everyday life. Energy management education (EME) is a group self-management intervention based on energy conservation and management strategies delivered by occupational therapists. Data on the effectiveness of EME in persons with long COVID-related fatigue still need to be provided. This study aims to investigate procedural and methodological parameters to plan a future study analyzing the effectiveness of EME in individuals with post-COVID-19 conditions.

MATERIALS AND METHODS: A pre-post design was used. The procedural data was collected regarding eligibility, reasons for participation decline, dropout, and follow-up rates. Changes in self-efficacy in using energy management strategies, fatigue impact, competency in daily activities, and quality of life were collected three times. Implemented behavior strategies at five months from EME were documented.

RESULTS: During five months, 17 of 30 eligible participants were included in the study. No dropouts were registered during the intervention period. The follow-up response rate was 70%. The effect size was large in three out of four outcomes post-intervention, with a tendency to increase at follow-up.

CONCLUSIONS: This study demonstrated the feasibility of study procedures and reported promising effect sizes for EME that should be further researched.}, } @article {pmid37543536, year = {2023}, author = {Baimukhamedov, C and Mirakhmedova, K and Dossybayeva, G}, title = {Long COVID: the time has come for globally acceptable definitions.}, journal = {Rheumatology international}, volume = {43}, number = {11}, pages = {2155-2156}, pmid = {37543536}, issn = {1437-160X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37541779, year = {2024}, author = {Ballesteros, O and Mark, S and Block, A and Mackin, L and Paul, S and Cooper, B and Abbott, M and Chang, S and Hammer, MJ and Levine, J and Pozzar, R and Snowberg, K and Tsai, K and Van Blarigan, E and Van Loon, K and Miaskowski, CA}, title = {COVID-19 pandemic stress and cancer symptom burden.}, journal = {BMJ supportive & palliative care}, volume = {13}, number = {e3}, pages = {e1351-e1362}, doi = {10.1136/spcare-2023-004319}, pmid = {37541779}, issn = {2045-4368}, mesh = {Humans ; *COVID-19/epidemiology ; Symptom Burden ; COVID-19 Vaccines ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Neoplasms/complications/epidemiology/diagnosis ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVES: In a sample of patients with cancer (n=1145) who were assessed during the height of the COVID-19 pandemic, latent profile analysis was used to identify subgroups of patients with distinct stress profiles and to evaluate for differences in demographic and clinical characteristics and symptom severity scores among these subgroups.

METHODS: Patients completed measures of cancer-specific and COVID-19 stress, global stress, social isolation, loneliness, depression, state and trait anxiety, morning and evening fatigue, morning and evening energy, sleep disturbance, cognitive function, and pain. Latent profile analysis was used to identify subgroups of patients with distinct stress profiles. Differences among the subgroups in study measures were evaluated using parametric and non-parametric tests.

RESULTS: Using clinically meaningful cut-off scores for the stress measures, four distinct stress profiles were identified (ie, none class (51.3%); low stress and moderate loneliness class (24.4%), high stress and moderate loneliness class (14.0%), and very high stress and moderately high loneliness class (high, 10.3%)). Risk factors associated with membership in the high class included: younger age, lower annual household income, lower functional status and higher comorbidity burden. The two worst stress profiles reported clinically meaningful levels of all of the common symptoms associated with cancer and its treatments.

CONCLUSION: Findings from this study, obtained prior to the availability of COVID-19 vaccines and anti-viral medications, provide important 'benchmark data' to evaluate for changes in stress and symptom burden in patients with cancer in the postvaccine era and in patients with long COVID-19.}, } @article {pmid37540896, year = {2023}, author = {Nicotra, A and Masserini, F and Calcaterra, F and Di Vito, C and Doneddu, PE and Pomati, S and Nobile-Orazio, E and Riva, A and Mavilio, D and Pantoni, L}, title = {What do we mean by long COVID? A scoping review of the cognitive sequelae of SARS-CoV-2 infection.}, journal = {European journal of neurology}, volume = {30}, number = {12}, pages = {3968-3978}, doi = {10.1111/ene.16027}, pmid = {37540896}, issn = {1468-1331}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Disease Progression ; Fatigue/etiology ; Cognition ; }, abstract = {BACKGROUND AND PURPOSE: Many COVID-19 patients report persistent symptoms, including cognitive disturbances. We performed a scoping review on this topic, focusing primarily on cognitive manifestations.

METHODS: Abstracts and full texts of studies published on PubMed (until May 2023) addressing cognitive involvement persisting after SARS-CoV-2 infection were reviewed, focusing on terms used to name the cognitive syndrome, reported symptoms, their onset time and duration, and testing batteries employed. Reported psychiatric symptoms, their assessment tools, and more general manifestations were also extracted.

RESULTS: Among the 947 records identified, 180 studies were included. Only one third of them used a label to define the syndrome. A minority of studies included patients according to stringent temporal criteria of syndrome onset (34%), whereas more studies reported a minimum required symptom duration (77%). The most frequently reported cognitive symptoms were memory and attentional-executive disturbances, and among psychiatric complaints, the most frequent were anxiety symptoms, depression, and sleep disturbances. Most studies reported fatigue among general symptoms. Thirty-six studies employed cognitive measures: screening tests alone (n = 19), full neuropsychological batteries (n = 25), or both (n = 29); 30 studies performed psychiatric testing. Cognitive deficits were demonstrated in 39% of subjects, the most frequently affected domains being attention/executive functions (90%) and memory (67%).

CONCLUSIONS: Currently, no agreement exists on a label for post-COVID-19 cognitive syndrome. The time of symptom onset after acute infection and symptom duration are still discussed. Memory and attention-executive complaints and deficits, together with fatigue, anxiety, and depression symptoms, are consistently reported, but the objective evaluation of these symptoms is not standardized.}, } @article {pmid37536948, year = {2023}, author = {Saigal, A and Nagoda Niklewicz, C and Naidu, SB and Bintalib, HM and Shah, AJ and Seligmann, G and Hunter, AS and Wey, E and Abubakar, I and Mahungu, T and Miller, D and Barnett, J and Jain, NG and Brill, S and Goldring, J and Jarvis, H and Smith, C and Ogbonnaya, C and Hurst, JR and Lipman, MCI and Mandal, S}, title = {Cross-sectional study evaluating the impact of SARS-CoV-2 variants on Long COVID outcomes in UK hospital survivors.}, journal = {BMJ open respiratory research}, volume = {10}, number = {1}, pages = {}, pmid = {37536948}, issn = {2052-4439}, mesh = {Adult ; Humans ; *SARS-CoV-2/genetics ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Hospitals ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVES: COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination.

DESIGN: Prospective observational cross-sectional study.

SETTING: Secondary care tertiary hospital in the UK.

PARTICIPANTS: This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021).

OUTCOME MEASURES: Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively.

RESULTS: 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44).

CONCLUSIONS: Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.}, } @article {pmid37536722, year = {2023}, author = {Tanne, JH}, title = {Covid-19: US agency launches raft of clinical trials of treatments for long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1797}, doi = {10.1136/bmj.p1797}, pmid = {37536722}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; }, } @article {pmid37536704, year = {2023}, author = {Nusbaum, NJ}, title = {Long COVID, Disability, and the Workplace.}, journal = {Southern medical journal}, volume = {116}, number = {8}, pages = {718-720}, pmid = {37536704}, issn = {1541-8243}, mesh = {Humans ; *COVID-19/epidemiology ; Workplace ; Retirement ; *Disabled Persons ; Employment ; }, abstract = {The long-term societal impact of coronavirus disease 2019 (COVID-19) includes not only those who have died from COVID-19 but also those who have survived with prolonged residual symptoms. "Long COVID" symptoms such as fatigue may impair an individual's ability to work, but gaps in disability law may leave such workers vulnerable to job loss and involuntary retirement.}, } @article {pmid37535946, year = {2023}, author = {Del Carpio-Orantes, L}, title = {[Proposal for a diagnostic approach to long COVID].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {61}, number = {4}, pages = {403-405}, pmid = {37535946}, issn = {2448-5667}, mesh = {Humans ; COVID-19 Testing ; *Post-Acute COVID-19 Syndrome/diagnosis ; Reagent Kits, Diagnostic ; }, abstract = {The objective of this communication is to provide a proposal for a diagnostic approach to persistent COVID based on the various current etiopathogenic theories and to serve as a guide on how to start the diagnostic process in a patient affected by this syndrome according to the prevailing symptomatology and the basic studies and of extension that can be requested and even assisted by commercial kits that would help a better diagnosis.}, } @article {pmid37534972, year = {2023}, author = {Yong, SJ and Halim, A and Halim, M and Ming, LC and Goh, KW and Alfaresi, M and AlShehail, BM and Al Fares, MA and Alissa, M and Sulaiman, T and Alsalem, Z and Alwashmi, ASS and Khamis, F and Al Kaabi, NA and Albayat, H and Alsheheri, A and Garout, M and Alsalman, J and Alfaraj, AH and Alhajri, M and Dhama, K and Alburaiky, LM and Alsanad, AH and AlShurbaji, AT and Rabaan, AA}, title = {Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {7}, pages = {655-667}, doi = {10.1080/13543784.2023.2242773}, pmid = {37534972}, issn = {1744-7658}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; *Fatigue Syndrome, Chronic/drug therapy ; Drugs, Investigational/therapeutic use ; }, abstract = {INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.

AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.

EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.}, } @article {pmid37534622, year = {2023}, author = {Zhang, L and Li, YH and Kibler, K and Kraberger, S and Varsani, A and Turk, J and Elmadbouly, N and Aliskevich, E and Spaccarelli, L and Estifanos, B and Enow, J and Zanetti, IR and Saldevar, N and Lim, E and Schlievert, J and Browder, K and Wilson, A and Juan, FA and Pinteric, A and Garg, A and Monder, H and Saju, R and Gisriel, S and Jacobs, B and Karr, TL and Florsheim, EB and Kumar, V and Wallen, J and Rahman, M and McFadden, G and Hogue, BG and Lucas, AR}, title = {Viral anti-inflammatory serpin reduces immuno-coagulopathic pathology in SARS-CoV-2 mouse models of infection.}, journal = {EMBO molecular medicine}, volume = {15}, number = {9}, pages = {e17376}, pmid = {37534622}, issn = {1757-4684}, support = {R01 AI080607/AI/NIAID NIH HHS/United States ; R01 AR074627/AR/NIAMS NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; *Serpins/therapeutic use/metabolism/pharmacology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Disease Models, Animal ; Peptide Hydrolases ; *Respiratory Distress Syndrome ; }, abstract = {SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.}, } @article {pmid37533859, year = {2023}, author = {Vlaicu, SI and Tatomir, A and Cuevas, J and Rus, V and Rus, H}, title = {COVID, complement, and the brain.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1216457}, pmid = {37533859}, issn = {1664-3224}, support = {R01 NS042011/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; *Complement Membrane Attack Complex/metabolism ; Endothelial Cells/metabolism ; SARS-CoV-2/metabolism ; *COVID-19 ; Brain/metabolism ; }, abstract = {The brains of COVID-19 patients are affected by the SARS-CoV-2 virus, and these effects may contribute to several COVID-19 sequelae, including cognitive dysfunction (termed "long COVID" by some researchers). Recent advances concerning the role of neuroinflammation and the consequences for brain function are reviewed in this manuscript. Studies have shown that respiratory SARS-CoV-2 infection in mice and humans is associated with selective microglial reactivity in the white matter, persistently impaired hippocampal neurogenesis, a decrease in the number of oligodendrocytes, and myelin loss. Brain MRI studies have revealed a greater reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, associated with a greater reduction in global brain size, in those with SARS-CoV-2 and a greater cognitive decline. COVID-19 can directly infect endothelial cells of the brain, potentially promoting clot formation and stroke; complement C3 seems to play a major role in this process. As compared to controls, the brain tissue of patients who died from COVID-19 have shown a significant increase in the extravasation of fibrinogen, indicating leakage in the blood-brain barrier; furthermore, recent studies have documented the presence of IgG, IgM, C1q, C4d, and C5b-9 deposits in the brain tissue of COVID-19 patients. These data suggest an activation of the classical complement pathway and an immune-mediated injury to the endothelial cells. These findings implicate both the classical and alternative complement pathways, and they indicate that C3b and the C5b-9 terminal complement complex (membrane attack complex, MAC) are acting in concert with neuroinflammatory and immune factors to contribute to the neurological sequelae seen in patients with COVID.}, } @article {pmid37532784, year = {2023}, author = {Cao, Q and Du, X and Jiang, XY and Tian, Y and Gao, CH and Liu, ZY and Xu, T and Tao, XX and Lei, M and Wang, XQ and Ye, LL and Duan, DD}, title = {Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.}, journal = {Acta pharmacologica Sinica}, volume = {44}, number = {12}, pages = {2347-2357}, pmid = {37532784}, issn = {1745-7254}, mesh = {Humans ; *Cardiovascular Diseases/genetics ; *COVID-19 ; Phenomics ; Precision Medicine ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; }, abstract = {SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.}, } @article {pmid37532165, year = {2023}, author = {Haig, AJ}, title = {ACRM Long Covid Information Forgot the "RM" Part?.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {11}, pages = {1966}, doi = {10.1016/j.apmr.2023.06.023}, pmid = {37532165}, issn = {1532-821X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37532164, year = {2023}, author = {Gross, M and Lansang, NM and Gopaul, U and Ogawa, EF and Heyn, PC and Santos, FH and Sood, P and Zanwar, PP and Schwertfeger, J and Cogan, AM and Akinwuntan, A and Faieta, J}, title = {Response to Letter to the Editor on "What Do I Need to Know About Long-Covid-related Fatigue, Brain Fog, and Mental Health Changes?".}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {11}, pages = {1966-1967}, doi = {10.1016/j.apmr.2023.07.008}, pmid = {37532164}, issn = {1532-821X}, support = {IK1 RX003636/RX/RRD VA/United States ; }, mesh = {Humans ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue/etiology ; Brain ; }, } @article {pmid37531071, year = {2023}, author = {Shaikh, A and Khan, SD and Baloch, F and Virani, SS and Samad, Z}, title = {The COVID-19 Pandemic and Coronary Heart Disease: the Next Surge.}, journal = {Current atherosclerosis reports}, volume = {25}, number = {9}, pages = {559-569}, pmid = {37531071}, issn = {1534-6242}, support = {U54 TW012089/TW/FIC NIH HHS/United States ; D43 TW011625/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Coronary Disease/epidemiology ; *Myocardial Infarction/epidemiology ; }, abstract = {PURPOSE OF REVIEW: In this narrative review, we highlight different ways in which the COVID-19 pandemic has impacted coronary heart disease (CHD) burden and how a surge in morbidity and mortality may be expected in the near future. We also discuss potential solutions, and the direction subsequent research and corrective actions should take.

RECENT FINDINGS: COVID-19 has been implicated in the development and worsening of CHD via acute and chronic mechanisms in the form of plaque rupture, destabilization, and sustenance of a chronic inflammatory state leading to long COVID syndrome and increased rates of myocardial infarction. However, indirectly the pandemic is likely to further escalate the CHD burden through poor health behaviors such as tobacco consumption, reduced physical activity, economic devastation and its associated sequelae, and regular cardiac care interruptions and delays. COVID-19 has increased the total CHD burden and will require extensive resource allocation and multifaceted strategies to curb future rise.}, } @article {pmid37530975, year = {2023}, author = {Kow, CS and Ramachandram, DS and Hasan, SS}, title = {Embracing Imatinib: a novel approach to safeguarding the endothelial barrier in patients with COVID-19.}, journal = {Angiogenesis}, volume = {26}, number = {4}, pages = {481-483}, pmid = {37530975}, issn = {1573-7209}, mesh = {Humans ; Imatinib Mesylate/pharmacology/therapeutic use ; *Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; *COVID-19 ; Pyrimidines/therapeutic use/pharmacology ; Piperazines/pharmacology ; Benzamides/therapeutic use/pharmacology ; }, abstract = {Imatinib, an ABL tyrosine-kinase inhibitor, shows promise in restoring endothelial barrier function in patients with COVID-19, thus, preventing cytokine leakage from the alveolar compartment to the systemic compartment. COVID-19 is characterized by an alveolar cytokine storm, and imatinib has been shown to strengthen the endothelial barrier and mitigate alveolar inflammatory responses by modulating NF-κB signaling. Incorporating imatinib into COVID-19 treatment strategies offers a novel approach to safeguard the endothelial barrier and address the complex pathophysiology of the disease, including its potential implications in long COVID. Given that endothelial dysfunction plays a central role in COVID-19 progression and long COVID development, protecting the endothelial barrier during acute infection is crucial in preventing the persistent endothelial dysfunction associated with long COVID.}, } @article {pmid37530064, year = {2023}, author = {Kwak, M and Mah, YJ}, title = {Comparison of characteristics of kick- and electric-scooter-related dental and maxillofacial injuries: A retrospective study.}, journal = {Dental traumatology : official publication of International Association for Dental Traumatology}, volume = {39}, number = {6}, pages = {565-574}, doi = {10.1111/edt.12875}, pmid = {37530064}, issn = {1600-9657}, mesh = {Humans ; Male ; *Fractures, Bone/epidemiology ; Head Protective Devices ; *Maxillofacial Injuries/epidemiology/etiology ; Pandemics ; Retrospective Studies ; Female ; Child, Preschool ; Child ; }, abstract = {BACKGROUND/AIM: Owing to the nearly three-year-long COVID-19 pandemic, small personal transportation devices that allow for greater freedom of movement within the cities have gained attention. Therefore, the number of people using kick or electric scooters has increased. This study aimed to compare the characteristics of kick and electric scooter-related dental and maxillofacial trauma and provide helpful information for preventing scooter accidents, appropriate treatment of patients with scooter-related trauma, and policy establishment.

MATERIALS AND METHODS: This retrospective observational study analysed the medical records of 310 patients who visited the emergency room of Ajou University Dental Hospital for kick and electric scooter-related oral and maxillofacial injuries between 1 January 2017 and 31 December 2022. Sex, age, scooter type, time, and mechanism of the accident, helmet use, alcohol consumption, dental and maxillofacial injury types, and treatment were analysed.

RESULTS: The average age in the kick-scooter group (5.71 ± 4.25) was lower than that in the electric-scooter group (28.24 ± 10.02) (p < .0001). There were more males in both groups. The helmet usage rates of the two groups were 2.80% and 7.88%, respectively. In the kick-scooter group, periodontal damage was more common than pulp injury, while in the electric-scooter group, pulp injury was more common than periodontal injury. There was no significant difference in soft-tissue damage between the two groups; however, bone fractures occurred significantly more frequently in the electric-scooter group (p < .0001).

CONCLUSIONS: Electric scooters cause more crown and bone fractures than kick scooters and require more active treatment of dental and maxillofacial injuries. Riders should use protective equipment to prevent dental and maxillofacial injury. Although there are regulations related to scooters, the effectiveness of both kick- and electric-scooter related laws needs to be evaluated.}, } @article {pmid37529783, year = {2023}, author = {Singh, PK and Sharma, VK and Lalwani, LK and Chaudhry, D and Govindagoudar, MB and Sriram, CP and Ahuja, A}, title = {Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study.}, journal = {Turkish journal of emergency medicine}, volume = {23}, number = {3}, pages = {149-155}, pmid = {37529783}, issn = {2452-2473}, abstract = {OBJECTIVES: Ongoing symptomatic coronavirus disease 2019 (OSC) is defined as persistent symptoms beyond 4 weeks of acute illness. OSC leads to prolonged hospitalization and oxygen dependence. We aimed to find the outcome of Janus kinase inhibitors (JAKi) as a steroid-sparing agent to treat OSC.

METHODS: In this single-center case-controlled study comparing JAKi and corticosteroids in OSC cases, data of 41 cases out of 86 were included - 21 in the JAKi group and 20 in the corticosteroid group from 4 weeks of acute illness to the next 4 weeks. Clinical parameters and inflammatory markers were recorded. The primary outcome was to compare the proportion of patients who were able to maintain oxygen saturation ≥95% with any oxygen supplementation in the two groups.

RESULTS: The baseline clinical and demographic characteristics were similar in the two groups. The age was 53.65 ± 9.8 years and 51.48 ± 14.0 years in the corticosteroid group and JAKi group, respectively. At the baseline, 85% of patients in the corticosteroid group and 85.8% in the JAKi group were on oxygen support. The most common symptom in both groups was breathlessness followed by cough. Twenty percent of patients in the JAKi group received baricitinib and the remaining were given tofacitinib. At the time of follow-up, the majority of cases had a significant reduction in C-reactive protein (CRP) and D-dimer; however, the change in CRP and D-dimer was similar in both groups. The number of patients off oxygen support at 4 weeks was higher in the JAKi group (85% in the corticosteroid group vs. 95.2% in the JAKi group, P = 0.269), and the median time to liberation from oxygen support was significantly lower in JAKi group (19 days in corticosteroid group vs. 9 days in JAKi group, P < 0.001). The frequency of any adverse event was also higher in the corticosteroid group (70% vs. 23.8%, P = 0.003).

CONCLUSION: JAKi can be used as immunomodulatory drugs in hypoxic OSC cases having evidence of ongoing inflammation.}, } @article {pmid37529714, year = {2023}, author = {Salvucci, F and Codella, R and Coppola, A and Zacchei, I and Grassi, G and Anti, ML and Nitisoara, N and Luzi, L and Gazzaruso, C}, title = {Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1202696}, pmid = {37529714}, issn = {2297-055X}, abstract = {INTRODUCTION: Long-COVID is a broadly defined condition and there are no effective therapies. Cardiovascular manifestations of long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of long-COVID, including in the mechanisms of its cardiovascular manifestations. The present study aimed to evaluate the effectiveness of a treatment with blockers of histamine receptors in patients with long-COVID who did not respond to other therapies.

METHODS: In all, 14 patients (F/M = 9/5; 49.5 ± 11.5 years) and 13 controls (F/M = 8/5; 47.3 ± 8.0 years) with long-COVID symptoms attributed to MCA were evaluated. Patients were treated with fexofenadine (180 mg/day) and famotidine (40 mg/day). Fatigue, brain fog, abdominal disorders, and increased heart rate were evaluated in treated and untreated patients at baseline and 20 days later.

RESULTS: Long-COVID symptoms disappeared completely in 29% of treated patients. There was a significant improvement in each of the considered symptoms (improved or disappeared) in all treated patients, and the improvement grade was significantly greater in treated patients compared to controls. No significant differences in the outcomes were observed in the controls.

CONCLUSIONS: Our data confirm that histamine receptors blockade may be an effective target to successfully treat long-COVID. Our finding supports the underlying role of MCA in the pathophysiology of long-COVID.}, } @article {pmid37529636, year = {2023}, author = {Barisione, G and Brusasco, V}, title = {Reply to: Lung pathophysiology in patients with long COVID-19: one size definitely does not fit all.}, journal = {ERJ open research}, volume = {9}, number = {4}, pages = {}, pmid = {37529636}, issn = {2312-0541}, abstract = {Lung pathophysiology in long COVID https://bit.ly/3IaPyS8.}, } @article {pmid37528203, year = {2023}, author = {Kozlov, M}, title = {NIH launches trials for long COVID treatments: what scientists think.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {37528203}, issn = {1476-4687}, } @article {pmid37528111, year = {2023}, author = {López-Hernández, Y and Monárrez-Espino, J and López, DAG and Zheng, J and Borrego, JC and Torres-Calzada, C and Elizalde-Díaz, JP and Mandal, R and Berjanskii, M and Martínez-Martínez, E and López, JA and Wishart, DS}, title = {The plasma metabolome of long COVID patients two years after infection.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {12420}, pmid = {37528111}, issn = {2045-2322}, support = {FS 148461//CIHR/Canada ; }, mesh = {Humans ; *Interleukin-17 ; Tandem Mass Spectrometry ; Chromatography, Liquid ; *COVID-19 ; SARS-CoV-2 ; Metabolome ; Metabolomics ; Post-Acute COVID-19 Syndrome ; }, abstract = {One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as "long COVID") which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.}, } @article {pmid37526809, year = {2024}, author = {Philippe, A and Günther, S and Rancic, J and Cavagna, P and Renaud, B and Gendron, N and Mousseaux, E and Hua-Huy, T and Reverdito, G and Planquette, B and Sanchez, O and Gaussem, P and Salmon, D and Diehl, JL and Smadja, DM}, title = {VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.}, journal = {Angiogenesis}, volume = {27}, number = {1}, pages = {51-66}, pmid = {37526809}, issn = {1573-7209}, support = {programme jeune talent//Mécénat Crédit Agricole Ile de France/ ; SARCODO Flash Covid//ANR and Fondation de France/ ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; *Post-Acute COVID-19 Syndrome ; Vascular Endothelial Growth Factor A ; von Willebrand Factor ; *COVID-19/diagnostic imaging ; SARS-CoV-2 ; Disease Progression ; Biomarkers ; }, abstract = {BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19.

OBJECTIVE: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19.

METHODS: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT).

RESULTS: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement.

CONCLUSION: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.}, } @article {pmid37526385, year = {2023}, author = {Zuin, M and Mazzitelli, M and Cattelan, A}, title = {Long-COVID: Is it time to revise the definition?.}, journal = {Journal of medical virology}, volume = {95}, number = {8}, pages = {e29011}, doi = {10.1002/jmv.29011}, pmid = {37526385}, issn = {1096-9071}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37525488, year = {2024}, author = {Goldenberg, DL}, title = {Applying Lessons From Rheumatology to Better Understand Long COVID.}, journal = {Arthritis care & research}, volume = {76}, number = {1}, pages = {49-56}, doi = {10.1002/acr.25210}, pmid = {37525488}, issn = {2151-4658}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; *Fibromyalgia/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; *Rheumatology ; *COVID-19 ; SARS-CoV-2 ; }, abstract = {Long COVID can sometimes be attributed to organ damage and well-characterized pathophysiology, but more often there is no evidence of organ damage or abnormal biomarkers. This is most evident in patients with mild to moderate initial SARS-CoV-2 infection who were not hospitalized. Their persistent symptoms are strikingly similar to those of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome, including fatigue, post-exertional malaise, myalgias/arthralgias, and sleep and cognitive disturbances in 50% to 100% of cases. Analogous pathophysiologic pathways in fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and long COVID include host-microbial interactions in the absence of direct tissue invasion and absence of systemic autoimmunity, with evidence for immune dysregulation as well as autonomic, peripheral, and central nervous system dysfunction. Current treatment of long COVID has been based on multidisciplinary management recommended for FM and ME/CFS and has been formalized and made widely available by funding for nationwide long COVID clinics. Long COVID and its treatment should be distinguished by the presence or absence of organ damage. The acknowledged role of patient engagement in research and open dialogue regarding work and disability noted in long COVID may have meaningful impact on patients with FM and ME/CFS. Hopefully, advances in basic long COVID research will aid in understanding FM and ME/CFS, and rheumatologists should thus be involved in such research and patient care.}, } @article {pmid37524570, year = {2023}, author = {Corona-Meraz, FI and Quintero-Castillo, BP and Hernández-Palma, LA and Machado-Sulbaran, AC}, title = {Long COVID-19 and Insulin Autoimmune Syndrome: A Case Report.}, journal = {Clinical therapeutics}, volume = {45}, number = {9}, pages = {e187-e192}, doi = {10.1016/j.clinthera.2023.06.026}, pmid = {37524570}, issn = {1879-114X}, abstract = {PURPOSE: To describe a case report of a patient with symptoms associated with metabolic alterations 1 month after having COVID-19.

METHODS: Laboratory tests, clinical evaluations, and body composition assessments were performed by specialists.

FINDINGS: The patient presented excessive sweating, hot flashes, dizziness, blurred vision, and seizure. Laboratory tests indicated low glucose levels after convulsions (50, 42.7, and 55 mg/dL), high insulin levels (basal, 638 µIU/mL; 2-hour, >1000 µU/mL), and positivity for anti-insulin antibodies. The patient was diagnosed with insulin autoimmune syndrome. Treatment with azathioprine and nutritional recommendations improved remission.

IMPLICATIONS: SARS-CoV-2 infection or vaccination might induce insulin tolerance failure.}, } @article {pmid37523396, year = {2023}, author = {Phu, DH and Maneerattanasak, S and Shohaimi, S and Trang, LTT and Nam, TT and Kuning, M and Like, A and Torpor, H and Suwanbamrung, C}, title = {Prevalence and factors associated with long COVID and mental health status among recovered COVID-19 patients in southern Thailand.}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0289382}, pmid = {37523396}, issn = {1932-6203}, mesh = {Adult ; Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; Thailand/epidemiology ; Cross-Sectional Studies ; SARS-CoV-2 ; Depression/epidemiology/etiology ; Anxiety/epidemiology/etiology ; Health Status ; }, abstract = {Mental health disorders have become a growing public health concern among individuals recovering from COVID-19. Long COVID, a condition where symptoms persist for an extended period, can predict psychological problems among COVID-19 patients. This study aimed to investigate the prevalence of long COVID and mental health status among Thai adults who had recovered from COVID-19, identify the association between the mental health status and long COVID symptoms, and investigate the risk factors associated with the correlation between long COVID and mental health outcomes. A cross-sectional study was conducted among 939 randomly selected participants in Nakhon Si Thammarat province, southern Thailand. The Depression, Anxiety, and Stress Scale-21 was used to investigate mental health symptoms, and a checklist comprised of thirteen common symptoms was used to identify the long COVID among participants. Logistic regression models were used to investigate the risk factors associated with mental health status and long COVID symptoms among participants. Among the 939 participants, 104 (11.1%) had depression, 179 (19.1%) had anxiety, and 42 (4.8%) were stressed. A total of 745 participants (79.3%) reported experiencing at least one symptom of long COVID, with fatigue (72.9%, SE±0.02), cough (66.0%, SE±0.02), and muscle pain (54.1%, SE±0.02) being the most frequently reported symptoms. All long COVID symptoms were significantly associated with mental health status. Shortness of breath, fatigue, and chest tightness were the highest risk factors for mental health status among COVID-19 patients. The final multivariable model indicated that female patients (OR = 1.89), medical history (OR = 1.92), and monthly income lower than 5,000 Thai baht (OR = 2.09) were associated with developing long COVID symptoms and mental health status (all p<0.01). This study provides valuable insights into the potential long-term effects of COVID-19 on mental health and enhances understanding of the mechanisms underlying the condition for predicting the occurrence of mental health issues in Thai COVID-19 patients.}, } @article {pmid37522912, year = {2023}, author = {Costa, UM}, title = {[Occupational Therapy Guideline for the management of sequelae of viral diseases with SARS-CoV-2 : Supplement to the S1 guidelines for the management of post-viral conditions exemplified by post-COVID-19].}, journal = {Wiener klinische Wochenschrift}, volume = {135}, number = {Suppl 4}, pages = {599-618}, pmid = {37522912}, issn = {1613-7671}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Occupational Therapy ; Quality of Life ; }, abstract = {Sequelae of viral disease with SARS-CoV-2 impact clients' biopsychosocial health, thus their daily life, with limitations resp. barriers in their occupational capacities and opportunities. Occupational therapists have numerous and, with constantly growing evidence, personalised therapeutic means, measures, and methods in any intervention phase relevant to these according health problems, supporting i. e. coping, occupational adaptation, quality of life and participatory re-shaping of (daily) life. Based on ongoing research findings and practice evidence, this document contains recommendations for occupational therapy intervention for clients with biopsychosocial health conditions post COVID-19.}, } @article {pmid37522243, year = {2023}, author = {Wang, Y and Zhao, D and Xiao, W and Shi, J and Chen, W and Jia, Q and Zhou, Y and Wang, R and Chen, X and Feng, L}, title = {Paxlovid reduces the risk of Long COVID in patients six months after hospital discharge.}, journal = {Journal of medical virology}, volume = {95}, number = {8}, pages = {e29014}, doi = {10.1002/jmv.29014}, pmid = {37522243}, issn = {1096-9071}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Patient Discharge ; *COVID-19 ; Hospitals ; }, } @article {pmid37521293, year = {2023}, author = {Stein, JA and Kaes, M and Smola, S and Schulz-Schaeffer, WJ}, title = {Neuropathology in COVID-19 autopsies is defined by microglial activation and lesions of the white matter with emphasis in cerebellar and brain stem areas.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1229641}, pmid = {37521293}, issn = {1664-2295}, abstract = {INTRODUCTION: This study aimed to investigate microglial and macrophage activation in 17 patients who died in the context of a COVID-19 infection in 2020 and 2021.

METHODS: Through immunohistochemical analysis, the lysosomal marker CD68 was used to detect diffuse parenchymal microglial activity, pronounced perivascular macrophage activation and macrophage clusters. COVID-19 patients were compared to control patients and grouped regarding clinical aspects. Detection of viral proteins was attempted in different regions through multiple commercially available antibodies.

RESULTS: Microglial and macrophage activation was most pronounced in the white matter with emphasis in brain stem and cerebellar areas. Analysis of lesion patterns yielded no correlation between disease severity and neuropathological changes. Occurrence of macrophage clusters could not be associated with a severe course of disease or preconditions but represent a more advanced stage of microglial and macrophage activation. Severe neuropathological changes in COVID-19 were comparable to severe Influenza. Hypoxic damage was not a confounder to the described neuropathology. The macrophage/microglia reaction was less pronounced in post COVID-19 patients, but detectable i.e. in the brain stem. Commercially available antibodies for detection of SARS-CoV-2 virus material in immunohistochemistry yielded no specific signal over controls.

CONCLUSION: The presented microglial and macrophage activation might be an explanation for the long COVID syndrome.}, } @article {pmid37521288, year = {2023}, author = {Paradiso, B and Limback, C and Su, T and Liao, W and Mpotsaris, A}, title = {Editorial: An update on neurological disorders post COVID-19 infection.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1229843}, pmid = {37521288}, issn = {1664-2295}, } @article {pmid37520724, year = {2023}, author = {George, MS and Sanchez, J and Rollings, C and Fear, D and Irving, P and Sinclair, LV and Schurich, A}, title = {Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function.}, journal = {iScience}, volume = {26}, number = {8}, pages = {107280}, pmid = {37520724}, issn = {2589-0042}, support = {/WT_/Wellcome Trust/United Kingdom ; COV/DUN/20/01/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV-T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.}, } @article {pmid37520419, year = {2023}, author = {Peghin, M and De Martino, M and Palese, A and Chiappinotto, S and Fonda, F and Gerussi, V and Sartor, A and Curcio, F and Grossi, PA and Isola, M and Tascini, C}, title = {Post-COVID-19 Syndrome 2 Years After the First Wave: The Role of Humoral Response, Vaccination and Reinfection.}, journal = {Open forum infectious diseases}, volume = {10}, number = {7}, pages = {ofad364}, pmid = {37520419}, issn = {2328-8957}, abstract = {BACKGROUND: The aim of this study was to describe the long-term evolution of post-COVID-19 syndrome over 2 years after the onset of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in survivors of the first wave.

METHODS: This prospective study was based on interviews and investigated post-COVID-19 syndrome 6, 12, and 24 months after the disease onset in all adult in- and outpatients with COVID-19 followed at Udine Hospital (Italy) during the first wave (March-May 2020). Humoral response, vaccination status, and reinfection were assessed.

RESULTS: Overall, 230 patients (53.5% female; mean age 54.7 years) were interviewed 2.3 years (standard deviation = 0.11) after acute onset. Post-COVID-19 syndrome was observed in 36.1% of patients (n = 83) at 2 years. The most common persistent symptoms were fatigue (14.4%), rheumatological (14.4%), and psychiatric symptoms (9.6%). Overall, 55.4% (46 of 83) of long haulers searched for healthcare system support and 21 (45.7%) were visited by a specialist. Female gender (odds ratio [OR] = 2.50, P = .005), a proportional increase in the number of symptoms during acute COVID-19 (OR = 1.40, P = .001), and the presence of comorbidities (OR = 1.57, P = .004) were all independent risk factors for post-COVID-19 syndrome. Vaccination and reinfection had no impact on post-COVID-19 syndrome dynamics. The presence of receptor-binding domain (RBD) SARS-CoV-2 immunoglobulin G (IgG) and non-RBD SARS-CoV-2 IgG titers were not associated with the occurrence of post-COVID-19 syndrome.

CONCLUSIONS: Two years after COVID-19, the burden of persistent symptoms remains high among in- and outpatients' population infected during the first wave. Post-COVID-19 dynamic does not seem to be influenced by SARS-CoV-2 immunization status and reinfection.}, } @article {pmid37519257, year = {2023}, author = {Abu-Ismail, L and Taha, MJJ and Abuawwad, MT and Al-Bustanji, Y and Al-Shami, K and Nashwan, A and Yassin, M}, title = {COVID-19 and Anemia: What Do We Know So Far?.}, journal = {Hemoglobin}, volume = {47}, number = {3}, pages = {122-129}, doi = {10.1080/03630269.2023.2236546}, pmid = {37519257}, issn = {1532-432X}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Anemia/etiology ; *Thrombosis ; Pandemics ; }, abstract = {On 11 March 2020, the World Health Organization (WHO) declared the novel SARS-CoV-2 virus responsible for causing COVID-19, a global pandemic. The virus primarily targets the respiratory system but can also affect other systems, notably causing hematological pathologies. Anemia, a common hematologic disorder, is characterized by the reduced oxygen-carrying capacity of red blood cells. The existing literature has a suspected link between anemia and severe COVID-19 cases. Researchers are currently investigating the long-term complications of COVID-19 in anemic patients, as these complications may play a crucial role in predicting patient prognosis. Anemic individuals are at a higher risk of experiencing severe COVID-19 infections due to several contributing pathophysiological mechanisms, including thrombotic, hemorrhagic, and autoimmune etiologies. The primary effect of these mechanisms is a decrease in circulating hemoglobin levels, reducing oxygen availability for cells. This exacerbates the hypoxia caused by COVID-19-induced acute respiratory distress syndrome (ARDS). This review offers a comprehensive overview of the evidence regarding the long-term complications of COVID-19 in anemic patients.}, } @article {pmid37516868, year = {2023}, author = {Nieuwland, JM and Nutma, E and Philippens, IHCHM and Böszörményi, KP and Remarque, EJ and Bakker, J and Meijer, L and Woerdman, N and Fagrouch, ZC and Verstrepen, BE and Langermans, JAM and Verschoor, EJ and Windhorst, AD and Bontrop, RE and de Vries, HE and Stammes, MA and Middeldorp, J}, title = {Longitudinal positron emission tomography and postmortem analysis reveals widespread neuroinflammation in SARS-CoV-2 infected rhesus macaques.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {179}, pmid = {37516868}, issn = {1742-2094}, mesh = {Animals ; Humans ; *SARS-CoV-2 ; Macaca mulatta ; Neuroinflammatory Diseases ; *COVID-19/diagnostic imaging ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; Positron-Emission Tomography ; Inflammation/diagnostic imaging ; Collagen Type IV ; Receptors, GABA ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) patients initially develop respiratory symptoms, but they may also suffer from neurological symptoms. People with long-lasting effects after acute infections with severe respiratory syndrome coronavirus 2 (SARS-CoV-2), i.e., post-COVID syndrome or long COVID, may experience a variety of neurological manifestations. Although we do not fully understand how SARS-CoV-2 affects the brain, neuroinflammation likely plays a role.

METHODS: To investigate neuroinflammatory processes longitudinally after SARS-CoV-2 infection, four experimentally SARS-CoV-2 infected rhesus macaques were monitored for 7 weeks with 18-kDa translocator protein (TSPO) positron emission tomography (PET) using [[18]F]DPA714, together with computed tomography (CT). The baseline scan was compared to weekly PET-CTs obtained post-infection (pi). Brain tissue was collected following euthanasia (50 days pi) to correlate the PET signal with TSPO expression, and glial and endothelial cell markers. Expression of these markers was compared to brain tissue from uninfected animals of comparable age, allowing the examination of the contribution of these cells to the neuroinflammatory response following SARS-CoV-2 infection.

RESULTS: TSPO PET revealed an increased tracer uptake throughout the brain of all infected animals already from the first scan obtained post-infection (day 2), which increased to approximately twofold until day 30 pi. Postmortem immunohistochemical analysis of the hippocampus and pons showed TSPO expression in cells expressing ionized calcium-binding adaptor molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and collagen IV. In the hippocampus of SARS-CoV-2 infected animals the TSPO[+] area and number of TSPO[+] cells were significantly increased compared to control animals. This increase was not cell type specific, since both the number of IBA1[+]TSPO[+] and GFAP[+]TSPO[+] cells was increased, as well as the TSPO[+] area within collagen IV[+] blood vessels.

CONCLUSIONS: This study manifests [[18]F]DPA714 as a powerful radiotracer to visualize SARS-CoV-2 induced neuroinflammation. The increased uptake of [[18]F]DPA714 over time implies an active neuroinflammatory response following SARS-CoV-2 infection. This inflammatory signal coincides with an increased number of TSPO expressing cells, including glial and endothelial cells, suggesting neuroinflammation and vascular dysregulation. These results demonstrate the long-term neuroinflammatory response following a mild SARS-CoV-2 infection, which potentially precedes long-lasting neurological symptoms.}, } @article {pmid37516715, year = {2023}, author = {Mikuteit, M and Baskal, S and Klawitter, S and Dopfer-Jablonka, A and Behrens, GMN and Müller, F and Schröder, D and Klawonn, F and Steffens, S and Tsikas, D}, title = {Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects.}, journal = {Amino acids}, volume = {55}, number = {9}, pages = {1173-1188}, pmid = {37516715}, issn = {1438-2199}, support = {Funding No: ZW7-85152953//The DEFEAT Corona project is funded by the European Fund for Regional Development (EFRD,)./ ; }, abstract = {In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography-mass spectrometry (GC-MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) N[G]-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = - 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.}, } @article {pmid37515140, year = {2023}, author = {Binetti, J and Real, M and Renzulli, M and Bertran, L and Riesco, D and Perpiñan, C and Mohedano, A and Segundo, RS and Ortiz, M and Porras, JA and Pineda, DR and Auguet, T}, title = {Clinical and Biomarker Profile Responses to Rehabilitation Treatment in Patients with Long COVID Characterized by Chronic Fatigue.}, journal = {Viruses}, volume = {15}, number = {7}, pages = {}, pmid = {37515140}, issn = {1999-4915}, mesh = {Humans ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Creatinine ; *Fatigue Syndrome, Chronic/therapy ; }, abstract = {Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered "responders" to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-vaccinated against SARS-CoV-2 presented a lower degree of fatigue. LC patients presented a favorable response to a supervised exercise program. Differences in creatinine and protein levels were observed between rehabilitation therapy "responders" and "nonresponders". A good state of protein nutrition was related to a better rehabilitation response. The results are promising regarding possible predictive biomarkers of rehabilitation response, such as creatinine.}, } @article {pmid37514997, year = {2023}, author = {Miteva, D and Kitanova, M and Batselova, H and Lazova, S and Chervenkov, L and Peshevska-Sekulovska, M and Sekulovski, M and Gulinac, M and Vasilev, GV and Tomov, L and Velikova, T}, title = {The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice.}, journal = {Vaccines}, volume = {11}, number = {7}, pages = {}, pmid = {37514997}, issn = {2076-393X}, support = {project № BG-RRP-2.004-0008-C01//the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria,/ ; }, abstract = {Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide.}, } @article {pmid37514967, year = {2023}, author = {Kamamuta, A and Takagi, Y and Takahashi, M and Kurihara, K and Shibata, H and Tanaka, K and Hata, K}, title = {Fatigue Potentially Reduces the Effect of Transcranial Magnetic Stimulation on Depression Following COVID-19 and Its Vaccination.}, journal = {Vaccines}, volume = {11}, number = {7}, pages = {}, pmid = {37514967}, issn = {2076-393X}, support = {KAKENHI 21H03327//Japan Society for the Promotion of Science/ ; KAKENHI 21H03327//Japan Society for the Promotion of Science/ ; 29303//The Watanabe Foundation/ ; }, abstract = {COVID-19's long-term effects, known as Long-COVID, present psychiatric and physical challenges in recovered patients. Similarly, rare long-term post-vaccination side effects, resembling Long-COVID, are emerging (called Post-Vaccine). However, effective treatments for both conditions are scarce. Our clinical experience suggests that transcranial magnetic stimulation (TMS) often aids recovery in Long-COVID and Post-Vaccine patients. However, its effectiveness is reduced in patients with severe fatigue. Therefore, we retrospectively analysed Tokyo TMS Clinic's outpatient records (60 in total; mean age, 38 years) to compare Long-COVID and post-vaccine patients' characteristics and symptoms, assess the impact of TMS on their symptoms, and investigate the role of fatigue in depression recovery with TMS. The primary outcome was the regression coefficient of the initial fatigue score on depression score improvement using TMS. Secondary outcomes included psychiatric/physical scores before and after TMS and their improvement rates. We found no differences in the initial symptoms and background factors between Long-COVID and Post-Vaccine patients. After ten TMS sessions, all psychiatric and physical symptom scores improved significantly. TMS improves depression, insomnia, anxiety, and related neuropsychiatric symptoms, which were the primary complaints in this study. Thus, we conclude that TMS improves depression and anxiety. The effectiveness of TMS in treating depression in Long-COVID and Post-Vaccine patients decreased as fatigue severity increased. In conclusion, TMS relieved depressive symptoms following COVID-19 and vaccination; however, fatigue may hinder its effectiveness.}, } @article {pmid37512801, year = {2023}, author = {Joseph, G and Cohen, C and Rubin, C and Murad, H and Indenbaum, V and Asraf, K and Weiss-Ottolenghi, Y and Segal-Lieberman, G and Kreiss, Y and Lustig, Y and Regev-Yochay, G}, title = {Humoral Immunity of Unvaccinated COVID-19 Recovered vs. Naïve BNT162b2 Vaccinated Individuals: A Prospective Longitudinal Study.}, journal = {Microorganisms}, volume = {11}, number = {7}, pages = {}, pmid = {37512801}, issn = {2076-2607}, abstract = {To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: -0.54 vs. -0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals.}, } @article {pmid37512587, year = {2023}, author = {Gama-Almeida, MC and Pinto, GDA and Teixeira, L and Hottz, ED and Ivens, P and Ribeiro, H and Garrett, R and Torres, AG and Carneiro, TIA and Barbalho, BO and Ludwig, C and Struchiner, CJ and Assunção-Miranda, I and Valente, APC and Bozza, FA and Bozza, PT and Dos Santos, GC and El-Bacha, T}, title = {Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19.}, journal = {Metabolites}, volume = {13}, number = {7}, pages = {}, pmid = {37512587}, issn = {2218-1989}, support = {314971/2021-1//National Council for Scientific and Technological Development/ ; 260003/002690/2020//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/200.930/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; E-26/201.259/2021//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; scholarship//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.}, } @article {pmid37512160, year = {2023}, author = {Massimino, M and Iaquinta, FS and Naty, S and Andreozzi, F and Grembiale, RD}, title = {Persistent Pancytopenia as a Long-COVID Manifestation in a Patient with Adult-Onset Still's Disease: A Case Report.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {7}, pages = {}, pmid = {37512160}, issn = {1648-9144}, mesh = {Adult ; Male ; Humans ; *Still's Disease, Adult-Onset/complications/diagnosis/drug therapy ; *Pancytopenia/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Background: Adult-onset Still's disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient's laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man's symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia.}, } @article {pmid37511933, year = {2023}, author = {Aloè, T and Novelli, F and Puppo, G and Pinelli, V and Barisione, E and Trucco, E and Costanzo, R and Covesnon, MG and Grillo, F and Zoccali, P and Milanese, M and Maniscalco, S and Tagliabue, E and Piroddi, IMG and Venturi, S and Serra, M and Scordamaglia, F and Ferrari, M and Serafini, A}, title = {Prevalence of Long COVID Symptoms Related to SARS-CoV-2 Strains.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37511933}, issn = {2075-1729}, abstract = {BACKGROUND: Few studies have assessed the differences of patterns of Long COVID (L-COVID) with regards to the pathogenetic SARS-CoV-2 strains.

OBJECTIVES: To investigate the relationship between demographic and clinical characteristics of acute phase of infection and the persistence of L-COVID symptoms and clinical presentation across different SARS-CoV-2 strains.

METHODS: In this observational-multicenter study we recorded all demographic and clinical characteristics, severity of infection, presence/persistence of symptoms of fatigue, dyspnoea and altered quality of life (QoL) at baseline and after 6 months, in a sample of Italian patients from Liguria between March 2020 and March 2022.

RESULTS: 308 patients (mean age 63.2 years; 55.5% men) with previous COVID were enrolled. Obese patients were 21.2% with a significant difference in obesity prevalence across the second and third wave (p = 0.012). Treatment strategies differed between waves (p < 0.001): more patients required invasive mechanical ventilation in the first wave, more patients were treated with high-flow nasal cannula/non-invasive ventilation in the in the second and more patients were treated with oxygen-therapy in the fourth wave. At baseline, a high proportion of patients were symptomatic (dyspnoea and fatigue), with impairment in some QoL indicators. A higher prevalence of patients with pain, were seen in the first wave compared to later infections (p = 0.01). At follow-up, we observed improvement of dyspnoea, fatigue and some dimensions of QoL scale evaluation such as mobility, usual activities, pain evaluations; instead there was no improvement in remaining QoL scale indicators (usual care and anxiety-depression).

CONCLUSIONS: There were no significant differences in the prevalence of the most frequent L-COVID symptoms, except for QoL pain domain that was especially associated with classical variant. Our results show substantial impact on social and professional life and usual care activities. These findings highlight the importance of multidisciplinary post COVID follow-up care including mental health support and rehabilitation program.}, } @article {pmid37511837, year = {2023}, author = {König, S and Vollenberg, R and Tepasse, PR}, title = {The Renin-Angiotensin System in COVID-19: Can Long COVID Be Predicted?.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37511837}, issn = {2075-1729}, abstract = {(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin system (RAS) is critically involved in their pathophysiology and is counter-balanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin system (KKS). Considerable research interest with respect to COVID-19 treatment is currently being directed towards the components of these systems. In earlier studies, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized COVID-19 patients and a subgroup of convalescent patients. The data had been obtained using labeled bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE. The data were supplemented with mass-spectrometry-based serum proteomic analysis. Here, we hypothesize that the degree of BK serum degradation could be indicative of Long COVID. (2) Review and Discussion: The recent literature is briefly reviewed. The fact that the levels of the BK serum degradation products did not reach normal concentrations in almost half of the patients during convalescences could have been partially due to a dysregulated RAS. (3) Conclusions: Standard tests for routine patient care in Long COVID come often back normal. We suggest that the measurement of selected members of the RAS such as ACE and angiotensin II or the use of our BK degradation assay could identify Long COVID candidates. Clinical studies are required to test this hypothesis.}, } @article {pmid37511753, year = {2023}, author = {Kotzalidis, GD and Ferrara, OM and Margoni, S and Ieritano, V and Restaino, A and Bernardi, E and Fischetti, A and Catinari, A and Monti, L and Chieffo, DPR and Simonetti, A and Sani, G}, title = {Are the Post-COVID-19 Posttraumatic Stress Disorder (PTSD) Symptoms Justified by the Effects of COVID-19 on Brain Structure? A Systematic Review.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511753}, issn = {2075-4426}, abstract = {COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.}, } @article {pmid37511673, year = {2023}, author = {Baalbaki, N and Blankestijn, JM and Abdel-Aziz, MI and de Backer, J and Bazdar, S and Beekers, I and Beijers, RJHCG and van den Bergh, JP and Bloemsma, LD and Bogaard, HJ and van Bragt, JJMH and van den Brink, V and Charbonnier, JP and Cornelissen, MEB and Dagelet, Y and Davies, EH and van der Does, AM and Downward, GS and van Drunen, CM and Gach, D and Geelhoed, JJM and Glastra, J and Golebski, K and Heijink, IH and Holtjer, JCS and Holverda, S and Houweling, L and Jacobs, JJL and Jonker, R and Kos, R and Langen, RCJ and van der Lee, I and Leliveld, A and Mohamed Hoesein, FAA and Neerincx, AH and Noij, L and Olsson, J and van de Pol, M and Pouwels, SD and Rolink, E and Rutgers, M and Șahin, H and Schaminee, D and Schols, AMWJ and Schuurman, L and Slingers, G and Smeenk, O and Sondermeijer, B and Skipp, PJ and Tamarit, M and Verkouter, I and Vermeulen, R and de Vries, R and Weersink, EJM and van de Werken, M and de Wit-van Wijck, Y and Young, S and Nossent, EJ and Maitland-van der Zee, AH and , }, title = {Precision Medicine for More Oxygen (P4O2)-Study Design and First Results of the Long COVID-19 Extension.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511673}, issn = {2075-4426}, support = {LSHM20104; LSHM20068//Health Holland/ ; }, abstract = {Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40-65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3-6 and 12-18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient's home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3-6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.}, } @article {pmid37511668, year = {2023}, author = {Piater, T and Gietl, M and Hofer, S and Gostner, JM and Sahanic, S and Tancevski, I and Sonnweber, T and Pizzini, A and Egger, A and Schennach, H and Loeffler-Ragg, J and Weiss, G and Kurz, K}, title = {Persistent Symptoms and IFN-γ-Mediated Pathways after COVID-19.}, journal = {Journal of personalized medicine}, volume = {13}, number = {7}, pages = {}, pmid = {37511668}, issn = {2075-4426}, support = {GZ 75759//Tyrolean Regional Government/ ; }, abstract = {After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (n = 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.}, } @article {pmid37511206, year = {2023}, author = {Vottero, P and Tavernini, S and Santin, AD and Scheim, DE and Tuszynski, JA and Aminpour, M}, title = {Computational Prediction of the Interaction of Ivermectin with Fibrinogen.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511206}, issn = {1422-0067}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Fibrin/metabolism ; *Fibrinogen/metabolism ; Hemostatics ; *Ivermectin/pharmacology/therapeutic use ; Molecular Docking Simulation ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2/metabolism ; *Thrombosis/metabolism ; }, abstract = {Hypercoagulability and formation of extensive and difficult-to-lyse microclots are a hallmark of both acute COVID-19 and long COVID. Fibrinogen, when converted to fibrin, is responsible for clot formation, but abnormal structural and mechanical clot properties can lead to pathologic thrombosis. Recent experimental evidence suggests that the spike protein (SP) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly bind to the blood coagulation factor fibrinogen and induce structurally abnormal blood clots with heightened proinflammatory activity. Accordingly, in this study, we used molecular docking and molecular dynamics simulations to explore the potential activity of the antiparasitic drug ivermectin (IVM) to prevent the binding of the SARS-CoV-2 SP to fibrinogen and reduce the occurrence of microclots. Our computational results indicate that IVM may bind with high affinity to multiple sites on the fibrinogen peptide, with binding more likely in the central, E region, and in the coiled-coil region, as opposed to the globular D region. Taken together, our in silico results suggest that IVM may interfere with SP-fibrinogen binding and, potentially, decrease the formation of fibrin clots resistant to degradation. Additional in vitro studies are warranted to validate whether IVM binding to fibrinogen is sufficiently stable to prevent interaction with the SP, and potentially reduce its thrombo-inflammatory effect in vivo.}, } @article {pmid37510852, year = {2023}, author = {Yamamoto, Y and Otsuka, Y and Tokumasu, K and Sunada, N and Nakano, Y and Honda, H and Sakurada, Y and Hasegawa, T and Hagiya, H and Otsuka, F}, title = {Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID.}, journal = {Journal of clinical medicine}, volume = {12}, number = {14}, pages = {}, pmid = {37510852}, issn = {2077-0383}, support = {JP22K20927//Japan Society for the Promotion of Science/ ; }, abstract = {OBJECTIVE: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19.

METHODS: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated.

RESULTS: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4-251.5) and no-fatigue group (86.7 μg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05).

CONCLUSIONS: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.}, } @article {pmid37510774, year = {2023}, author = {Golomb, BA and Han, JH and Langsjoen, PH and Dinkeloo, E and Zemljic-Harpf, AE}, title = {Statin Use in Relation to COVID-19 and Other Respiratory Infections: Muscle and Other Considerations.}, journal = {Journal of clinical medicine}, volume = {12}, number = {14}, pages = {}, pmid = {37510774}, issn = {2077-0383}, support = {R01 HL063055/HL/NHLBI NIH HHS/United States ; RO1 HL63055-05/NH/NIH HHS/United States ; }, abstract = {Statins have been widely advocated for use in COVID-19 based on large favorable observational associations buttressed by theoretical expected benefits. However, past favorable associations of statins to pre-COVID-19 infection outcomes (also buttressed by theoretical benefits) were unsupported in meta-analysis of RCTs, RR = 1.00. Initial RCTs in COVID-19 appear to follow this trajectory. Healthy-user/tolerator effects and indication bias may explain these disparities. Moreover, cholesterol drops in proportion to infection severity, so less severely affected individuals may be selected for statin use, contributing to apparent favorable statin associations to outcomes. Cholesterol transports fat-soluble antioxidants and immune-protective vitamins. Statins impair mitochondrial function in those most reliant on coenzyme Q10 (a mevalonate pathway product also transported on cholesterol)-i.e., those with existing mitochondrial compromise, whom data suggest bear increased risks from both COVID-19 and from statins. Thus, statin risks of adverse outcomes are amplified in those patients at risk of poor COVID-19 outcomes-i.e., those in whom adjunctive statin therapy may most likely be given. High reported rates of rhabdomyolysis in hospitalized COVID-19 patients underscore the notion that statin-related risks as well as benefits must be considered. Advocacy for statins in COVID-19 should be suspended pending clear evidence of RCT benefits, with careful attention to risk modifiers.}, } @article {pmid37510324, year = {2023}, author = {Fernández-de-Las-Peñas, C and Arendt-Nielsen, L and Díaz-Gil, G and Gómez-Esquer, F and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Palomar-Gallego, MA and Pellicer-Valero, OJ and Giordano, R}, title = {Apolipoprotein E (ApoE) ε4 Genotype (ApoE rs429358-ApoE rs7412 Polymorphisms) Is Not Associated with Long COVID Symptoms in Previously Hospitalized COVID-19 Survivors.}, journal = {Genes}, volume = {14}, number = {7}, pages = {}, pmid = {37510324}, issn = {2073-4425}, mesh = {Humans ; Apolipoprotein E2/genetics ; Apolipoprotein E4/genetics ; *Apolipoproteins E/genetics ; *COVID-19/genetics ; Genotype ; *Post-Acute COVID-19 Syndrome/genetics ; SARS-CoV-2 ; }, abstract = {The role of genetics as a predisposing factor related to an increased risk of developing long COVID symptomatology is under debate. The aim of the current secondary analysis was to identify the association between the Apolipoprotein E (ApoE) gene, a gene affecting cholesterol metabolism and previously associated with a higher risk of SARS-CoV-2 infection and COVID-19 severity, and the development of long COVID in a cohort of individuals who had been hospitalized by SARS-CoV-2 infection. Unstimulated whole saliva samples were collected from 287 previously hospitalized COVID-19 survivors. Three genotypes of the ApoE gene (ApoE ε2, ε3, ε4) were obtained based on the combination of ApoE rs429358 and ApoE rs7412 polymorphisms. Participants were asked to self-report the presence of any post-COVID symptom in a face-to-face interview at 17.8 ± 5.2 months after hospital discharge and medical records were obtained. Each participant reported 3.0 (1.9) post-COVID symptoms. Overall, no significant differences in long COVID symptoms were observed depending on the ApoE genotype (ApoE ε2, ApoE ε3, ApoE ε4). The presence of the ApoE ε4 genotype, albeit associated with a higher risk of SARS-CoV-2 infection and COVID-19 severity, did not appear to predispose for the presence of long COVID in our cohort of previously hospitalized COVID-19 survivors.}, } @article {pmid37510097, year = {2023}, author = {Hameed, R and Bahadur, AR and Singh, SB and Sher, J and Todua, M and Moradi, LM and Bastakoti, S and Arslan, M and Ajmal, H and Lee, GY and Ayubcha, C and Werner, TJ and Alavi, A and Revheim, ME}, title = {Neurological and Psychiatric Manifestations of Long COVID-19 and Their [[18]F]FDG PET Findings: A Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {14}, pages = {}, pmid = {37510097}, issn = {2075-4418}, support = {T32 GM007753/GM/NIGMS NIH HHS/United States ; }, abstract = {For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [[18]F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [[18]F]FDG PET literature in this area.}, } @article {pmid37509643, year = {2023}, author = {Cojocaru, E and Cojocaru, C and Vlad, CE and Eva, L}, title = {Role of the Renin-Angiotensin System in Long COVID's Cardiovascular Injuries.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509643}, issn = {2227-9059}, abstract = {The renin-angiotensin system (RAS) is one of the biggest challenges of cardiovascular medicine. The significance of the RAS in the chronic progression of SARS-CoV-2 infection and its consequences is one of the topics that are currently being mostly discussed. SARS-CoV-2 undermines the balance between beneficial and harmful RAS pathways. The level of soluble ACE2 and membrane-bound ACE2 are both upregulated by the endocytosis of the SARS-CoV-2/ACE2 complex and the tumor necrosis factor (TNF)-α-converting enzyme (ADAM17)-induced cleavage. Through the link between RAS and the processes of proliferation, the processes of fibrous remodelling of the myocardium are initiated from the acute phase of the disease, continuing into the long COVID stage. In the long term, RAS dysfunction may cause an impairment of its beneficial effects leading to thromboembolic processes and a reduction in perfusion of target organs. The main aspects of ACE2-a key pathogenic role in COVID-19 as well as the mechanisms of RAS involvement in COVID cardiovascular injuries are studied. Therapeutic directions that can be currently anticipated in relation to the various pathogenic pathways of progression of cardiovascular damage in patients with longCOVID have also been outlined.}, } @article {pmid37509504, year = {2023}, author = {Fernández-de-Las-Peñas, C and Cancela-Cilleruelo, I and Rodríguez-Jiménez, J and Fuensalida-Novo, S and Martín-Guerrero, JD and Pellicer-Valero, OJ and de-la-Llave-Rincón, AI}, title = {Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study.}, journal = {Biomedicines}, volume = {11}, number = {7}, pages = {}, pmid = {37509504}, issn = {2227-9059}, support = {LONG COVID EXP//Comunidad de Madrid/ ; }, abstract = {Fatigue and dyspnoea are common post-COVID symptoms. The aim of this study was to apply Sankey plots and exponential bar plots for visualizing the evolution and trajectory of post-COVID fatigue and dyspnoea symptoms in a cohort of previously hospitalized COVID-19 survivors. A total of 1266 previously hospitalized patients due to COVID-19 participated in this multicentre study. They were assessed at hospital admission (T0), 8.4 months (T1), 13.2 months (T2) and 18.3 months (T3) after hospital discharge and were asked about the presence of self-reported fatigue or dyspnoea symptoms. Fatigue was defined as a self-perceived feeling of constant tiredness and/or weakness whereas dyspnoea was defined as a self-perceived feeling of shortness of breath at rest. We specifically asked for fatigue and dyspnoea that participants attributed to the infection. Clinical/hospitalization data were collected from hospital medical records. The prevalence of post-COVID fatigue was 56.94% (n = 721) at T1, 52.31% (n = 662) at T2 and 42.66% (n = 540) at T3. The prevalence of dyspnoea at rest decreased from 28.71% (n = 363) at hospital admission (T0), to 21.29% (n = 270) at T1, to 13.96% (n = 177) at T2 and 12.04% (n = 153) at T3. The Sankey plots revealed that 469 (37.08%) and 153 (12.04%) patients exhibited fatigue and dyspnoea at all follow-up periods. The recovery exponential curves show a decreased prevalence trend, showing that fatigue and dyspnoea recover the following three years after hospitalization. The regression models revealed that the female sex and experiencing the symptoms (e.g., fatigue, dyspnoea) at T1 were factors associated with the presence of post-COVID fatigue or dyspnoea at T2 and T3. The use of Sankey plots shows a fluctuating evolution of post-COVID fatigue and dyspnoea during the first two years after infection. In addition, exponential bar plots revealed a decreased prevalence of these symptoms during the first years after. The female sex is a risk factor for the development of post-COVID fatigue and dyspnoea.}, } @article {pmid37508966, year = {2023}, author = {Colizzi, M and Peghin, M and De Martino, M and Bontempo, G and Chiappinotto, S and Fonda, F and Isola, M and Tascini, C and Balestrieri, M and Palese, A}, title = {COVID-19 Survivors Are Still in Need of Neuropsychiatric Support Two Years after Infection.}, journal = {Brain sciences}, volume = {13}, number = {7}, pages = {}, pmid = {37508966}, issn = {2076-3425}, support = {20178S4EK9//PRIN/ ; }, abstract = {COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed (p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22-8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40-7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12-2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.}, } @article {pmid37508945, year = {2023}, author = {Chung, TW and Zhang, H and Wong, FK and Sridhar, S and Lee, TM and Leung, GK and Chan, KH and Lau, KK and Tam, AR and Ho, DT and Cheng, VC and Yuen, KY and Hung, IF and Mak, HK}, title = {A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.}, journal = {Brain sciences}, volume = {13}, number = {7}, pages = {}, pmid = {37508945}, issn = {2076-3425}, support = {//Shaw Foundation Hong Kong/ ; //Michael Seak-Kan Tong/ ; //Richard Yu and Carol Yu/ ; //May Tam Mak Mei Yin/ ; //Jessie & George Ho Charitable Foundation/ ; //Perfect Shape Medical Limited/ ; //Respiratory Viral Research Foundation/ ; //Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited/ ; SZSM201911014//Sanming Project of Medicine in Shenzhen, China/ ; //High Level-Hospital Program, Health Commission of Guangdong Province, China/ ; //Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for the Department of Health of the Hong Kong Special Administrative Region Government, China/ ; T11/707/15//Theme-Based Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region Government, China/ ; }, abstract = {Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.}, } @article {pmid37508724, year = {2023}, author = {Pinto Pereira, SM and Nugawela, MD and McOwat, K and Dalrymple, E and Xu, L and Ladhani, SN and Simmons, R and Chalder, T and Swann, O and Ford, T and Heyman, I and Segal, T and Semple, MG and Rojas, NK and CLoCk Consortium, and Shafran, R and Stephenson, T}, title = {Symptom Profiles of Children and Young People 12 Months after SARS-CoV-2 Testing: A National Matched Cohort Study (The CLoCk Study).}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {37508724}, issn = {2227-9067}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Although 99% of children and young people have been exposed to SARS-CoV-2, the long-term prevalence of post-COVID-19 symptoms in young people is unclear. The aim of this study is to describe symptom profiles 12 months after SARS-CoV-2 testing.

METHOD: A matched cohort study of a national sample of 20,202 children and young people who took a SARS-CoV-2 PCR test between September 2020 and March 2021.

RESULTS: 12 months post-index-test, there was a difference in the number of symptoms reported by initial negatives who never tested positive (NN) compared to the other three groups who had at least one positive test (p < 0.001). Similarly, 10.2% of the NN group described five-plus symptoms at 12 months compared to 15.9-24.0% in the other three groups who had at least one positive test. The most common symptoms were tiredness, sleeping difficulties, shortness of breath, and headaches for all four groups. For all these symptoms, the initial test positives with subsequent reports of re-infection had higher prevalences than other positive groups (p < 0.001). Symptom profiles, mental health, well-being, fatigue, and quality of life did not vary by vaccination status.

CONCLUSIONS: Following the pandemic, many young people, particularly those that have had multiple SARS-CoV-2 positive tests, experience a range of symptoms that warrant consideration and potential investigation and intervention.}, } @article {pmid37508686, year = {2023}, author = {Miraglia Del Giudice, M and Klain, A and Dinardo, G and D'Addio, E and Bencivenga, CL and Fontanella, C and Decimo, F and Umano, GR and Siciliano, M and Carotenuto, M and Indolfi, C}, title = {Behavioral and Sleep Disorders in Children and Adolescents following COVID-19 Disease: A Case-Control Study.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {37508686}, issn = {2227-9067}, abstract = {INTRODUCTION: Recent studies show that neuropsychiatric disorders are the most frequent sequelae of COVID-19 in children.

PURPOSE: Our work aimed to evaluate the impact of SARS-CoV-2 infection on behavior and sleep in children and adolescents.

MATERIALS AND METHODS: We enrolled 107 patients aged 1.5-18 years who contracted COVID-19 between one year and one month prior to data collection, referred to the University of Campania Luigi Vanvitelli in Italy. We asked their parents to complete two standardized questionnaires for the assessment of behavior (Child Behavior CheckList (CBCL)) and sleep (Sleep Disturbance Scale for Children (SLDS)). We analysed and compared the results with a control group (pre-COVID-19 pandemic).

RESULTS: In the COVID-19 group, the major results were found for sleep breathing disorders, sleep-wake transition disorders and disorders of initiating and maintaining sleep for the SDSC questionnaire, and internalizing scale, total scale and anxiety/depression for the CBCL questionnaire. The comparison of the CBCL results of the cases with the controls revealed statistically significant differences for the following items: internalizing scale, externalizing scale, somatic complaints, total score, thought problems [(p < 0.01)], anxious/depressed problems and withdrawn [(p < 0.001)].

CONCLUSIONS: COVID-19 has impacted children's and adolescents' mental health. Adolescents were the most affected patient group for internalizing problems, including anxiety and depression.}, } @article {pmid37507580, year = {2023}, author = {Kuchler, T and Günthner, R and Ribeiro, A and Hausinger, R and Streese, L and Wöhnl, A and Kesseler, V and Negele, J and Assali, T and Carbajo-Lozoya, J and Lech, M and Schneider, H and Adorjan, K and Stubbe, HC and Hanssen, H and Kotilar, K and Haller, B and Heemann, U and Schmaderer, C}, title = {Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation.}, journal = {Angiogenesis}, volume = {26}, number = {4}, pages = {547-563}, pmid = {37507580}, issn = {1573-7209}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/complications ; SARS-CoV-2 ; Retinal Vessels ; *Vascular Diseases ; Inflammation ; }, abstract = {BACKGROUND: Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.

METHODS: In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).

MEASUREMENTS AND MAIN RESULTS: PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5-190.2] vs. 189.1 [179.4-197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8-0.9] vs. 0.88 [0.8-0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = - 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.

CONCLUSION: Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.

TRIAL REGISTRATION: This study was previously registered at ClinicalTrials ("All Eyes on PCS-Analysis of the Retinal Microvasculature in Patients with Post-COVID-19 Syndrome". NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552). Persistent endothelial dysfunction in post-COVID-19 syndrome. Acute SARS-CoV-2 infection indirectly or directly causes endotheliitis in patients. N = 41 PCS patients were recruited and retinal vessel analysis was performed to assess microvascular endothelial function. Images of SVA and DVA are illustrative for RVA data analysis. For each PCS patient and healthy cohort, venular vessel diameter of the three measurement cycles was calculated and plotted on a diameter-time curve. Patients exhibited reduced flicker-induced dilation in veins (vFID) measured by dynamic vessel analysis (DVA) and lower central retinal arteriolar equivalent (CRAE) and arteriolar-venular ratio (AVR) and a tendency towards higher central retinal venular equivalent (CRVE) when compared to SARS-CoV-2 infection naïve participants. Created with BioRender.com.}, } @article {pmid37507151, year = {2023}, author = {The Lancet Infectious Diseases, }, title = {Where are the long COVID trials?.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {8}, pages = {879}, doi = {10.1016/S1473-3099(23)00440-1}, pmid = {37507151}, issn = {1474-4457}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37505636, year = {2023}, author = {Rescalvo-Casas, C and Pérez-Tanoira, R and Villegas, RF and Hernando-Gozalo, M and Seijas-Pereda, L and Pérez-García, F and Moríñigo, HM and Gómez-Herruz, P and Arroyo, T and González, R and Expósito, CV and Lledó García, L and Cabrera, JR and Cuadros-González, J}, title = {Clinical Evolution and Risk Factors in Patients Infected during the First Wave of COVID-19: A Two-Year Longitudinal Study.}, journal = {Tropical medicine and infectious disease}, volume = {8}, number = {7}, pages = {}, pmid = {37505636}, issn = {2414-6366}, support = {DIABECOV-CM//Community of Madrid with European Union funds against the COVID-19 pandemic/ ; }, abstract = {A limited number of longitudinal studies have examined the symptoms associated with long-COVID-19. We conducted an assessment of symptom onset, severity and patient recovery, and determined the percentage of patients who experienced reinfection up to 2 years after the initial onset of the disease. Our cohort comprises 377 patients (≥18 years) with laboratory-confirmed COVID-19 in a secondary hospital (Madrid, Spain), throughout March 3-16, 2020. Disease outcomes and clinical data were followed-up until August 12, 2022. We reviewed the evolution of the 253 patients who had survived as of April 2020 (67.1%). Nine died between April 2020 and August 2022. A multivariate regression analysis performed to detect the risk factors associated with long-COVID-19 revealed that the increased likelihood was associated with chronic obstructive lung disease (OR 14.35, 95% CI 1.89-109.09; p = 0.010), dyspnea (5.02, 1.02-24.75; p = 0.048), higher LDH (3.23, 1.34-7.52; p = 0.006), and lower D-dimer levels (0.164, 0.04-0.678; p = 0.012). Reinfected patients (n = 45) (47.8 years; 39.7-67.2) were younger than non-reinfected patients (64.1 years; 48.6-74.4)) (p < 0.001). Patients who received a combination of vaccines exhibited fewer symptoms (44.4%) compared to those who received a single type of vaccine (77.8%) (p = 0.048). Long-COVID-19 was detected in 27.05% (66/244) of patients. The early detection of risk factors helps predict the clinical course of patients with COVID-19. Middle-aged adults could be susceptible to reinfection, highlighting the importance of prevention and control measures regardless of vaccination status.}, } @article {pmid37504553, year = {2023}, author = {Schnekenberg, L and Sedghi, A and Schoene, D and Pallesen, LP and Barlinn, J and Woitek, F and Linke, A and Puetz, V and Barlinn, K and Mangner, N and Siepmann, T}, title = {Assessment and Therapeutic Modulation of Heart Rate Variability: Potential Implications in Patients with COVID-19.}, journal = {Journal of cardiovascular development and disease}, volume = {10}, number = {7}, pages = {}, pmid = {37504553}, issn = {2308-3425}, abstract = {Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts.}, } @article {pmid37504520, year = {2023}, author = {Yeung-Luk, BH and Narayanan, GA and Ghosh, B and Wally, A and Lee, E and Mokaya, M and Wankhade, E and Zhang, R and Lee, B and Park, B and Resnick, J and Jedlicka, A and Dziedzic, A and Ramanathan, M and Biswal, S and Pekosz, A and Sidhaye, VK}, title = {SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human respiratory epithelial cells mediated by expression of spike protein.}, journal = {mBio}, volume = {14}, number = {4}, pages = {e0082023}, pmid = {37504520}, issn = {2150-7511}, support = {R01HL124099, HLR01HL151107//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 5U01ES026721//HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; }, mesh = {Humans ; *COVID-19/metabolism ; SARS-CoV-2/metabolism ; Actins/metabolism ; Spike Glycoprotein, Coronavirus/genetics/metabolism ; Post-Acute COVID-19 Syndrome ; Epithelial Cells/metabolism ; Mitochondria ; }, abstract = {Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, SCV2), which has resulted in higher morbidity and mortality rate than other respiratory viral infections, such as Influenza A virus (IAV) infection. Investigating the molecular mechanisms of SCV2-host infection vs IAV is vital in exploring antiviral drug targets against SCV2. We assessed differential gene expression in human nasal cells upon SCV2 or IAV infection using RNA sequencing. Compared to IAV, we observed alterations in both metabolic and cytoskeletal pathways suggestive of epithelial remodeling in the SCV2-infected cells, reminiscent of pathways activated as a response to chronic injury. We found that spike protein interaction with the epithelium was sufficient to instigate these epithelial responses using a SCV2 spike pseudovirus. Specifically, we found downregulation of the mitochondrial markers SIRT3 and TOMM22. Moreover, SCV2 spike infection increased extracellular acidification and decreased oxygen consumption rate in the epithelium. In addition, we observed cytoskeletal rearrangements with a reduction in the actin-severing protein cofilin-1 and an increase in polymerized actin, indicating epithelial cytoskeletal rearrangements. This study revealed distinct epithelial responses to SCV2 infection, with early mitochondrial dysfunction in the host cells and evidence of cytoskeletal remodeling that could contribute to the worsened outcome in COVID-19 patients compared to IAV patients. These changes in cell structure and energetics could contribute to cellular resilience early during infection, allowing for prolonged cell survival and potentially paving the way for more chronic symptoms. IMPORTANCE COVID-19 has caused a global pandemic affecting millions of people worldwide, resulting in a higher mortality rate and concerns of more persistent symptoms compared to influenza A. To study this, we compare lung epithelial responses to both viruses. Interestingly, we found that in response to SARS-CoV-2 infection, the cellular energetics changed and there were cell structural rearrangements. These changes in cell structure could lead to prolonged epithelial cell survival, even in the face of not working well, potentially contributing to the development of chronic symptoms. In summary, these findings represent strategies utilized by the cell to survive the infection but result in a fundamental shift in the epithelial phenotype, with potential long-term consequences, which could set the stage for the development of chronic lung disease or long COVID-19.}, } @article {pmid37504295, year = {2023}, author = {Wilson, GN}, title = {A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes.}, journal = {Current issues in molecular biology}, volume = {45}, number = {7}, pages = {6003-6023}, pmid = {37504295}, issn = {1467-3045}, abstract = {A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.}, } @article {pmid37504277, year = {2023}, author = {Zaira, B and Yulianti, T and Levita, J}, title = {Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors.}, journal = {Current issues in molecular biology}, volume = {45}, number = {7}, pages = {5725-5740}, pmid = {37504277}, issn = {1467-3045}, abstract = {In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10-20% of these survivors have been reported to encounter long-term health problems, defined as 'long COVID-19', e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence. At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation. Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.}, } @article {pmid37504137, year = {2023}, author = {Barra, M and Tomaiuolo, G and Villella, VR and Esposito, S and Liboà, A and D'Angelo, P and Marasso, SL and Cocuzza, M and Bertana, V and Camilli, E and Preziosi, V}, title = {Organic Electrochemical Transistor Immuno-Sensors for Spike Protein Early Detection.}, journal = {Biosensors}, volume = {13}, number = {7}, pages = {}, pmid = {37504137}, issn = {2079-6374}, support = {FISR2020IP_01635//FISR COVID 2020/ ; }, mesh = {Humans ; *COVID-19/diagnosis ; Spike Glycoprotein, Coronavirus ; Pandemics ; SARS-CoV-2 ; Transistors, Electronic ; *Biosensing Techniques ; Proteins ; }, abstract = {The global COVID-19 pandemic has had severe consequences from the social and economic perspectives, compelling the scientific community to focus on the development of effective diagnostics that can combine a fast response and accurate sensitivity/specificity performance. Presently available commercial antigen-detecting rapid diagnostic tests (Ag-RDTs) are very fast, but still face significant criticisms, mainly related to their inability to amplify the protein signal. This translates to a limited sensitive outcome and, hence, a reduced ability to hamper the spread of SARS-CoV-2 infection. To answer the urgent need for novel platforms for the early, specific and highly sensitive detection of the virus, this paper deals with the use of organic electrochemical transistors (OECTs) as very efficient ion-electron converters and amplifiers for the detection of spike proteins and their femtomolar concentration. The electrical response of the investigated OECTs was carefully analyzed, and the changes in the parameters associated with the transconductance (i.e., the slope of the transfer curves) in the gate voltage range between 0 and 0.3 V were found to be more clearly correlated with the spike protein concentration. Moreover, the functionalization of OECT-based biosensors with anti-spike and anti-nucleocapside proteins, the major proteins involved in the disease, demonstrated the specificity of these devices, whose potentialities should also be considered in light of the recent upsurge of the so-called "long COVID" syndrome.}, } @article {pmid37503595, year = {2023}, author = {Goel, N and Goyal, N and Spalgais, S and Mrigpuri, P and Varma-Basil, M and Khanna, M and Nagaraja, R and Menon, B and Kumar, R}, title = {Initial COVID-19 Severity and Long-COVID Manifestations: An Observational Analysis.}, journal = {Thoracic research and practice}, volume = {24}, number = {1}, pages = {22-28}, pmid = {37503595}, issn = {2979-9139}, abstract = {OBJECTIVE: New-onset or persistent symptoms beyond after 4 weeks from COVID-19 are termed "long-COVID." Whether the initial severity of COVID-19 has a bearing on the clinicoradiological manifestations of long COVID is an area of interest.

MATERIAL AND METHODS: We did an observational analysis of the long-COVID patients after categorizing them based on their course of COVID-19 illness into mild, moderate, and severe groups. The clinical and radiological profile was compared across these groups.

RESULTS: Out of 150 long-COVID patients recruited in the study, about 79% (118), 14% (22), and 7% (10) had a history of mild, moderate, and severe COVID-19, respectively. Fatigue (P = .001), breathlessness (P = .001), tachycardia (P = .002), tachypnea (P < .001), raised blood pressure (P < .001), crepitations (P = .04), hypoxia at rest (P < .001), significant desaturation in 6-minute walk test (P = .27), type 1 respiratory failure (P = .001), and type 2 respiratory failure (P = .001) were found to be significantly higher in the long-COVID patients with a history of severe COVID-19. These patients also had the highest prevalence of abnormal chest X-ray (60%) and honeycombing in computed tomography scan thorax (25%, P = .027).

CONCLUSION: The course of long COVID bears a relationship with initial COVID-19 severity. Patients with severe COVID-19 are prone to develop more serious long-COVID manifestations.}, } @article {pmid37502886, year = {2023}, author = {Zhang, W and Gorelik, AJ and Wang, Q and Norton, SA and Hershey, T and Agrawal, A and Bijsterbosch, JD and Bogdan, R}, title = {Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37502886}, issn = {2692-8205}, support = {R01 AG061162/AG/NIA NIH HHS/United States ; R21 AA027827/AA/NIAAA NIH HHS/United States ; R01 NS109487/NS/NINDS NIH HHS/United States ; U01 DA055367/DA/NIDA NIH HHS/United States ; R01 DK126826/DK/NIDDK NIH HHS/United States ; R01 HD070855/HD/NICHD NIH HHS/United States ; R01 DA054750/DA/NIDA NIH HHS/United States ; R01 MH128286/MH/NIMH NIH HHS/United States ; }, abstract = {COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N=416 including n=224 COVID-19 cases; Mage=58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF).We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing. COVID-19 case status was not significantly associated with DBSI-RF (|β|'s<0.28, pFDR >0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (β's>0.3, all pFDR=0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology. Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.}, } @article {pmid37502361, year = {2023}, author = {García de Guadiana-Romualdo, L and Andaluz Ojeda, D}, title = {Editorial: Inflammation and organic damage in COVID-19: what have we learned 2 years into the pandemic?.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1238804}, pmid = {37502361}, issn = {2296-858X}, } @article {pmid37501626, year = {2023}, author = {AlMuhaissen, S and Abu Libdeh, A and ElKhatib, Y and Alshayeb, R and Jaara, A and Bardaweel, SK}, title = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and COVID-19: is there a connection?.}, journal = {Current medical research and opinion}, volume = {39}, number = {8}, pages = {1119-1126}, doi = {10.1080/03007995.2023.2242244}, pmid = {37501626}, issn = {1473-4877}, mesh = {Humans ; Adolescent ; *Fatigue Syndrome, Chronic/epidemiology/diagnosis ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; Chronic Disease ; }, abstract = {OBJECTIVES: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic systemic disease that leads to neurological, immunological, autonomic, and energy metabolism dysfunction. COVID-19 has been reported to cause similar symptoms to ME/CFS. The study aims to investigate the prevalence of myalgic encephalomyelitis in patients post-COVID-19 infection by assessing acute and long-term COVID-19 symptoms.

METHODS: A cross-sectional questionnaire was developed based on the ME/CFS diagnostic criteria, as specified by the IOM clinical diagnostic criteria, and administered to participants with confirmed COVID-19 who are more than 18 years old and have BMI below 40 Kg/m[2]. Data from 437 participants were completed.

RESULTS: The current study results revealed that 8.1% of the study participants met the ME/CFS diagnostic criteria. Interestingly, 2.8 of the study participants were classified to have COVID-19 related to ME/CFS. While 4.6% of participants were determined to have disease-related fatigue, 0.7% of participants showed ME/CFS that was not related to COVID-19, and 3.7% of participants were considered to have long COVID-19. Almost one-fourth of the study participants had a family history of ME/CFS. The current study demonstrated that the prevalence of ME/CFS is similar to slightly higher than reported in the literature.

CONCLUSION: The presence of a relationship between ME/CFS and COVID-19 has been supported by the results of our study. Follow-up of COVID-19 patients is strongly recommended to ensure proper management of ME/CFS symptoms.}, } @article {pmid37501054, year = {2023}, author = {Montenegro, YHA and Bobermin, LD and Sesterheim, P and Salvato, RS and Anschau, F and de Oliveira, MJS and Wyse, ATS and Netto, CA and Gonçalves, CS and Quincozes-Santos, A and Leipnitz, G}, title = {Serum of COVID-19 patients changes neuroinflammation and mitochondrial homeostasis markers in hippocampus of aged rats.}, journal = {Journal of neurovirology}, volume = {29}, number = {5}, pages = {577-587}, pmid = {37501054}, issn = {1538-2443}, support = {0643/2020//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 21/2551-0000067-8//FAPERGS/ ; }, mesh = {Humans ; Animals ; Rats ; *COVID-19/genetics ; Neuroinflammatory Diseases ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Homeostasis ; Hippocampus ; }, abstract = {Patients affected by COVID-19 present mostly with respiratory symptoms but acute neurological symptoms are also commonly observed. Furthermore, a considerable number of individuals develop persistent and often remitting symptoms months after infection, characterizing the condition called long-COVID. Since the pathophysiology of acute and persistent neurological manifestations is not fully established, we evaluated the expression of different genes in hippocampal slices of aged rats exposed to the serum of a post-COVID (sPC) individual and to the serum of patients infected by SARS-CoV-2 [Zeta (sZeta) and Gamma (sGamma) variants]. The expression of proteins related to inflammatory process, redox homeostasis, mitochondrial quality control and glial reactivity was determined. Our data show that the exposure to sPC, sZeta and sGamma differentially altered the mRNA levels of most inflammatory proteins and reduced those of antioxidant response markers in rat hippocampus. Furthermore, a decrease in the expression of mitochondrial biogenesis genes was induced by all serum samples, whereas a reduction in mitochondrial dynamics was only caused by sPC. Regarding the glial reactivity, S100B expression was modified by sPC and sZeta. These findings demonstrate that changes in the inflammatory response and a reduction of mitochondrial biogenesis and dynamics may contribute to the neurological damage observed in COVID-19 patients.}, } @article {pmid37497655, year = {2023}, author = {Udomsinprasert, W and Nontawong, N and Saengsiwaritt, W and Panthan, B and Jiaranai, P and Thongchompoo, N and Santon, S and Runcharoen, C and Sensorn, I and Jittikoon, J and Chaikledkaew, U and Chantratita, W}, title = {Host genetic polymorphisms involved in long-term symptoms of COVID-19.}, journal = {Emerging microbes & infections}, volume = {12}, number = {2}, pages = {2239952}, pmid = {37497655}, issn = {2222-1751}, mesh = {Humans ; *COVID-19/genetics ; Interleukin-10/genetics ; Angiotensin-Converting Enzyme 2/genetics ; Genetic Predisposition to Disease ; Post-Acute COVID-19 Syndrome ; Polymorphism, Single Nucleotide ; }, abstract = {Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms of Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide polymorphisms (SNPs) in 37 candidate genetic variants and clinical consequences of COVID-19 - especially long-term symptoms, Long COVID. A total of 260 COVID-19 patients, divided into mild (n = 239) and severe (n = 21) and further categorized based on the presence of Long COVID (no, n = 211; yes, n = 49), were recruited. Genotyping of selected polymorphisms responsible for viral entry, immune response, and inflammation was performed using MassARRAY system. Out of 37 SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA allele, nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA genotype, LZTFL1 rs17713054 A allele, interleukin-10 (IL10) rs1800896 TC genotype and C allele, angiotensin converting enzyme-2 (ACE2) rs2285666 T allele, and plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG genotype and G allele were significantly associated with an increased risk of developing Long COVID, whereas interleukin-10 receptor subunit beta (IL10RB) rs8178562 GG genotype was significantly associated with a reduced risk of Long COVID. Kaplan-Meier curve displayed that the above gene polymorphisms were significantly associated with cumulative rate of Long COVID occurrence. Polymorphisms in LZTFL1 rs10490770, LZTFL1 rs11385942, LZTFL1 rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, and IL10RB rs8178562 appear to be genetic factors involved in development of Long COVID.}, } @article {pmid37497527, year = {2022}, author = {Sotiriadou, M and Birka, S and Oikonomidou, E and Κouzoukidou, E and Mpogiatzidis, P}, title = {First insights from patients presenting with long/post-COVID syndrome in primary care: an exploratory report.}, journal = {Hippokratia}, volume = {26}, number = {4}, pages = {138-142}, pmid = {37497527}, issn = {1108-4189}, abstract = {BACKGROUND: Following the global pandemic of coronavirus disease 2019 (COVID-19), the long COVID or post-COVID syndrome refers to a relatively complex novel clinical entity. We conducted this study to assess the primary epidemiological features, main symptoms, and comorbidities probably related to this syndrome in patients referred to our long/post-COVID primary care unit during the initial months of its operation.

METHODS AND MATERIAL: This single-center prospective observational study was conducted between April 2022 and December 2022 and enrolled 71 patients (33 men, 38 women) who were examined due to persisting symptoms after recovering from COVID-19 infection, with the mean time of the first visit estimated at 3.12 ± 2.41 months from their acute COVID-19 illness. A thorough medical history, clinical examination, laboratory, and any other tests were performed on all patients when necessary.

RESULTS: The most common symptoms of long/post-COVID reported were fatigue (63.4 %), a persistent cough (45.1 %), stress manifestations (42.3 %), arthralgia or myalgia (33.8 %), tachycardia (32.4 %), depression manifestations (29.6 %), exertional dyspnea (28.2 %), and sleep disorders (25.4 %). Hypertension (in about 40 %) and the presence of five or more symptoms during the acute COVID-19 illness (in approximately 52 %) could be regarded as factors increasing the long/post-COVID appearance. The long/post-COVID syndrome affects even patients not experiencing severe COVID-19 illness. Unvaccinated patients are at higher risk of severe COVID-19 (p =0.014), higher risk of hospitalization (p =0.002), and in higher need of respiratory support with high flow (p =0.017) when compared to vaccinated ones. Hospitalized patients appear to be older than outpatients (59 ± 12.42 vs 52.78 ± 11.48 years of age; p =0.032.

CONCLUSION: The long/post-COVID syndrome is an established clinical entity, and several clinical features, symptoms, and patient profiles have to be assessed from the initial medical contact in primary care to exclude early any other clinical conditions and offer guided therapeutic strategies to those patients. HIPPOKRATIA 2022, 26 (4):138-142.}, } @article {pmid37497433, year = {2023}, author = {Martinez, MS and Ferreyra, FN and Paira, DA and Rivero, VE and Olmedo, JJ and Tissera, AD and Molina, RI and Motrich, RD}, title = {COVID-19 associates with semen inflammation and sperm quality impairment that reverses in the short term after disease recovery.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1220048}, pmid = {37497433}, issn = {1664-042X}, abstract = {Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than in women. However, cumulative reported data about the putative consequences on the male reproductive tract and fertility are controversial. Furthermore, the long-term effects of SARS-CoV-2 infection are still uncertain. Methods: In this study, we prospectively evaluated levels of inflammatory cytokines and leukocytes in semen and sperm quality parameters in a cohort of 231 reproductive-aged male patients, unvaccinated, who had recovered from mild or severe COVID-19 and in 62 healthy control individuals. Sperm quality was assessed early (less than 3 months) and long (more than 3 and up to 6 months) after having COVID-19. Interestingly, and unlike most reported studies, available extensive background and baseline data on patients' sperm quality allowed performing a more accurate analysis of COVID-19 effects on sperm quality. Results: Significantly higher levels of IL-1β, TNF and IFNγ were detected in semen from patients recently recovered from mild and/or severe COVID-19 with respect to control individuals indicating semen inflammation. Moreover, patients recovered from mild and/or severe COVID-19 showed significantly reduced semen volume, lower total sperm counts, and impaired sperm motility and viability. Interestingly, all observed alterations returned to baseline values after 3 or more months after disease recovery. Discussion: These results indicate that COVID-19 associates with semen inflammation and impaired semen quality early after disease. However, long COVID-19 seems not to include long-term detrimental consequences on male fertility potential since the observed alterations were reversible after 1-2 spermatogenesis cycles. These data constitute compelling evidence allowing a better understanding of COVID-19 associated sequelae, fundamental for semen collection in assisted reproduction.}, } @article {pmid37496702, year = {2023}, author = {Thompson, M and Ferrando, SJ and Dornbush, R and Lynch, S and Shahar, S and Klepacz, L and Smiley, A}, title = {Impact of COVID-19 on employment: sociodemographic, medical, psychiatric and neuropsychological correlates.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1150734}, pmid = {37496702}, issn = {2673-6861}, abstract = {INTRODUCTION: Given the nature of the persistent physical and neuropsychiatric symptoms reported in the literature, among individuals after acute COVID illness; there is growing concern about the functional implications of the Post-Acute Sequelae of COVID-19 (PASC). We aim to evaluate associations of sociodemographic, medical, psychiatric and neuropsychological factors with employment status post COVID-19.

METHODS: 59 participants were administered a neuropsychiatric assessment and queried about employment status and occupational difficulties months after quarantine. Two levels of comparison were conducted: (1) Those who took time off work (TTO) to those with no time off (NTO); (2) Those who reported occupational performance suffered (PS) to those who did not (PDNS).

RESULTS: TTO vs. NTO exhibited extensive differences across medical, psychiatric and neurocognitive domains. PS vs. PDNS differed on subjective measures of physical and cognitive symptoms, but not on objective testing.

CONCLUSION: Individuals who took time off beyond COVID-19 quarantine experience persistent physical, psychiatric, subjective and objective neurocognitive burden. In contrast, occupational impairment appears to reflect subjective complaints, but not objective measures. Clinical implications are discussed.}, } @article {pmid37496529, year = {2023}, author = {Kalava, A and Benyahia, SA and Tico Calzada, R and Staat, CM}, title = {Efficacy of Stellate Ganglion Block in Treating Long-Term COVID-19-Related Olfactory and Gustatory Dysfunction: A Case Series.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40929}, pmid = {37496529}, issn = {2168-8184}, abstract = {Olfactory and gustatory dysfunction, including anosmia, parosmia, ageusia, and dysgeusia, are common long-term symptoms of coronavirus disease 2019 (COVID-19) infection. These symptoms can have a severe impact on quality of life of a patient, including psychological well-being. Stellate ganglion block (SGB) has recently been explored as a potential therapeutic intervention for these symptoms. In this case series, we present six patients with long-term COVID-19 symptoms and we detail how their symptoms evolved after an SGB. All SGB were performed under ultrasound guidance by the same physician. Patients had a right SGB during the initial visit, followed by a left SGB at a subsequent visit. All but one patient reported improvements in olfaction and gustation after the SGB. Our findings suggest that SGB may be a promising therapeutic intervention for patients with olfactory and gustatory dysfunction related to long-term COVID-19 symptoms. Further research is needed to confirm these findings and to explore the optimal treatment protocol.}, } @article {pmid37495260, year = {2023}, author = {Dawson, C and Clunie, G and Evison, F and Duncan, S and Whitney, J and Houchen-Wolloff, L and Bolton, CE and Leavy, OC and Richardson, M and Omer, E and McAuley, H and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Greening, NJ and Nolan, CM and Wootton, DG and Daynes, E and Donaldson, G and Sargent, J and Scott, J and Pimm, J and Bishop, L and McNarry, M and Hart, N and Evans, RA and Singh, S and Yates, T and Chalder, T and Man, W and Harrison, E and Docherty, A and Lone, NI and Quint, JK and Chalmers, J and Ho, LP and Horsley, AR and Marks, M and Poinasamy, K and Raman, B and Wain, LV and Brightling, C and , and Sharma, N and Coffey, M and Kulkarni, A and Wallace, S}, title = {Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.}, journal = {BMJ open respiratory research}, volume = {10}, number = {1}, pages = {}, pmid = {37495260}, issn = {2052-4439}, support = {MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Female ; Humans ; Aftercare ; Cognition ; Communication ; *COVID-19/epidemiology ; Hospitalization ; Patient Discharge ; Prevalence ; Prospective Studies ; Male ; }, abstract = {OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19.

DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations.

SETTING: 64 UK acute hospital Trusts.

PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19.

MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise.

RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001).

CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.}, } @article {pmid37495241, year = {2023}, author = {Al-Oraibi, A and Woolf, K and Fatimah, S and Pareek, M}, title = {Healthcare workers must be included in long covid research in the UK.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1721}, doi = {10.1136/bmj.p1721}, pmid = {37495241}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Health Personnel ; United Kingdom/epidemiology ; }, } @article {pmid37494026, year = {2023}, author = {Suran, M}, title = {HHS Urges Primary Care Clinicians to Help Patients Manage Long COVID's Mental Health Symptoms.}, journal = {JAMA}, volume = {330}, number = {7}, pages = {581-582}, doi = {10.1001/jama.2023.13605}, pmid = {37494026}, issn = {1538-3598}, mesh = {Humans ; COVID-19/complications/psychology/therapy ; *Mental Disorders/etiology/therapy ; Mental Health ; *Post-Acute COVID-19 Syndrome/complications/psychology/therapy ; *Primary Health Care ; United States ; United States Dept. of Health and Human Services ; }, } @article {pmid37493802, year = {2023}, author = {Liu, EN and Yang, JH and Patel, L and Arora, J and Gooding, A and Ellis, R and Graves, JS}, title = {Longitudinal analysis and treatment of neuropsychiatric symptoms in post-acute sequelae of COVID-19.}, journal = {Journal of neurology}, volume = {270}, number = {10}, pages = {4661-4672}, pmid = {37493802}, issn = {1432-1459}, support = {P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; Anxiety/etiology ; *COVID-19/complications ; Fatigue/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; *Sleep Initiation and Maintenance Disorders/epidemiology/etiology ; Male ; }, abstract = {BACKGROUND: Persistent neuropsychiatric symptoms following acute COVID-19 infection are frequently reported. These include anxiety, depression, difficulty concentrating, fatigue, and insomnia. The longitudinal evolution of this neuropsychiatric burden is poorly understood and clinical guidelines concerning treatment are lacking.

OBJECTIVE: We sought to describe the longitudinal evolution of neuropsychiatric symptoms in the post-acute sequelae of COVID-19 (PASC) syndrome and examine symptom treatment at a single center.

METHODS: Consecutive participants experiencing persistent neurologic symptoms after acute COVID-19 infection were recruited from October 2020 to July 2022. Data collected included COVID-19 infection history, neurological exam and review of systems, Montreal Cognitive Assessment (MoCA), and self-reported surveys concerning neuropsychiatric symptoms and treatment. Data were collected at baseline and at 1-year follow-up.

RESULTS: A total of 106 participants (mean age 48.6, females 67%) were included in the study. At 1-year follow-up, 72.5% of participants reported at least one neuropsychiatric symptom. Over half (52.5%) of participants reported persistent fatigue. At baseline, 38.8% of all participants had met the established MoCA cut-off score of < 26 for mild cognitive impairment; this decreased to 20.0% at 1 year. COVID-19 infection severity was associated with neuro-PASC symptoms (including fatigue and anxiety) at 1 year. Overall, 29% of participants started at least one new medication for COVID-19-associated neuropsychiatric symptoms. Of the participants who started new medications, fatigue was the most common indication (44.8%) followed by insomnia (27.6%).

CONCLUSIONS: Neuropsychiatric symptoms related to neuro-PASC improve over time but can persist for over a year post-recovery. Most treatment modalities targeted neuro-PASC fatigue.}, } @article {pmid37492483, year = {2023}, author = {Toussaint, LL and Bratty, AJ}, title = {Amygdala and Insula Retraining (AIR) Significantly Reduces Fatigue and Increases Energy in People with Long COVID.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2023}, number = {}, pages = {7068326}, pmid = {37492483}, issn = {1741-427X}, abstract = {Long COVID affects approximately 10-30% of individuals after an acute COVID-19 infection (Ceban, Ling, et al. 2022; Ortona and Malorni, 2022). Numerous symptoms, including extreme fatigue, can persist for months, resulting in social and economic hardship for individuals and their families (Ortona and Malorni 2022). Therefore, approaches that offer some relief from Long COVID are urgently needed. Research suggests that Long COVID symptoms are akin to those of chronic conditions, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and are likely caused by inflammation and immune dysfunction (Scordo et al., 2021). Amygdala and Insula Retraining (AIR), a neuroplasticity program, has successfully alleviated chronic conditions (Gupta 2010; Sanabria-Mazo et al. 2020; Toussaint et al. 2012). In this randomized controlled trial, AIR was tested against a structurally equivalent health and wellness intervention for its effectiveness in treating the symptom of fatigue among Long COVID sufferers. Results showed a significant decrease in participants' fatigue and a significant increase in their energy after the 3-month AIR intervention. Additionally, the AIR group experienced more significant outcomes than the active control group. The AIR group demonstrated a fatigue reduction effect size four times that of the active control group, and the absolute reduction in mean scores for the AIR group was more than double that of the control group. Furthermore, the AIR group showed an effect size in energy enhancement twice that of the active control group, and the absolute increase in energy mean scores for the AIR group was almost double that of the control group. These novel findings suggest AIR is a viable means of reducing fatigue and increasing energy among Long COVID patients. Limitations and future research are discussed.}, } @article {pmid37492442, year = {2023}, author = {Lauria, A and Carfì, A and Benvenuto, F and Bramato, G and Ciciarello, F and Rocchi, S and Rota, E and Salerno, A and Stella, L and Tritto, M and Di Paola, A and Pais, C and Tosato, M and Janiri, D and Sani, G and Lo Monaco, R and Pagano, FC and Fantoni, M and Bernabei, R and Landi, F and Bizzarro, A and , }, title = {Neuropsychological measures of post-COVID-19 cognitive status.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1136667}, pmid = {37492442}, issn = {1664-1078}, abstract = {BACKGROUND: COVID-19 may result in persistent symptoms in the post-acute phase, including cognitive and neurological ones. The aim of this study is to investigate the cognitive and neurological features of patients with a confirmed diagnosis of COVID-19 evaluated in the post-acute phase through a direct neuropsychological evaluation.

METHODS: Individuals recovering from COVID-19 were assessed in an out-patient practice with a complete neurological evaluation and neuropsychological tests (Mini-Mental State Examination; Rey Auditory Verbal Test, Multiple Feature Target Cancellation Test, Trial Making Test, Digit Span Forward and Backward, and Frontal Assessment Battery). Pre- and post-COVID-19 global and mental health status was assessed along with the history of the acute phase of infection. Post-COVID-19 cognitive status was modeled by combining persistent self-reported COVID-related cognitive symptoms and pathologic neuropsychological tests.

RESULTS: A total of 406 individuals (average age 54.5 ± 15.1 years, 45.1% women) were assessed on average at 97.8 ± 48.0 days since symptom onset. Persistent self-reported neurological symptoms were found in the areas of sleep (32%), attention (31%), and memory (22%). The MMSE mean score was 28.6. In total, 84 subjects (20.7%) achieved pathologic neuropsychological test results. A high prevalence of failed tests was found in digit span backward (18.7%), trail making (26.6%), and frontal assessment battery (10.9%). Cognitive status was associated with a number of factors including cardiovascular disease history, persistent fatigue, female sex, age, anxiety, and mental health stress.

CONCLUSION: COVID-19 is capable of eliciting persistent measurable neurocognitive alterations particularly relevant in the areas of attention and working memory. These neurocognitive disorders have been associated with some potentially treatable factors and others that may stratify risk at an early stage.}, } @article {pmid37491810, year = {2023}, author = {Zuin, M and Mazzitelli, M and Rigatelli, G and Bilato, C and Cattelan, AM}, title = {Risk of ischemic stroke in patients recovered from COVID-19 infection: A systematic review and meta-analysis.}, journal = {European stroke journal}, volume = {8}, number = {4}, pages = {915-922}, pmid = {37491810}, issn = {2396-9881}, mesh = {Male ; Adult ; Humans ; Female ; *COVID-19/complications ; *Ischemic Stroke/epidemiology ; SARS-CoV-2 ; *Stroke/epidemiology ; }, abstract = {BACKGROUND: Data regarding the risk of ischemic stroke within 1 year after the post-acute phase of COVID-19 remain scant. We assess the risk of ischemic stroke in COVID-19 survivors after SARS-CoV-2 infection by performing a systematic review and meta-analysis of the available data.

METHODS: Following the PRISMA guidelines, we searched Medline and Scopus to locate all articles published up to February 11, 2023, reporting the risk of incident ischemic stroke in adult patients recovered from COVID-19 infection compared to non-infected patients (controls) defined as those who did not experience the infection over the same follow-up period. Ischemic stroke risk was evaluated using the Mantel-Haenszel random effects models with adjusted Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I[2] statistic.

RESULTS: Overall, 23,559,428 patients (mean age 56, 1 year, 54.3% males), of whom 1,595,984 had COVID-19, were included. Over a mean follow-up of 9.2 months, ischemic stroke occurred in 4.40 [95% CI: 4.36-4.43] out of 1000 patients survived to COVID-19 compared to 3.25 [95% CI:3.21-3.29] out of 1000 controls. Recovered COVID-19 patients presented a higher risk of ischemic stroke ((HR: 2.06, 95% CI: 1.75-2.41, p < 0.0001, I[2] = 63.7%) compared to people who did not have COVID-19. COVID-19 patients hospitalized at the time of the infection have a subsequent higher risk of stroke during the follow-up compared to those non-hospitalized.

CONCLUSIONS: Recovered COVID-19 patients have a higher risk of ischemic stroke compared to subjects from the general population within 9 months from the index infection.}, } @article {pmid37491461, year = {2023}, author = {Su, S and Zhao, Y and Zeng, N and Liu, X and Zheng, Y and Sun, J and Zhong, Y and Wu, S and Ni, S and Gong, Y and Zhang, Z and Gao, N and Yuan, K and Yan, W and Shi, L and Ravindran, AV and Kosten, T and Shi, J and Bao, Y and Lu, L}, title = {Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update.}, journal = {Molecular psychiatry}, volume = {28}, number = {10}, pages = {4056-4069}, pmid = {37491461}, issn = {1476-5578}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.}, } @article {pmid37491142, year = {2023}, author = {Peiris, S and Izcovich, A and Ordunez, P and Luciani, S and Martinez, C and Aldighieri, S and Reveiz, L}, title = {Challenges to delivering evidence-based management for long COVID.}, journal = {BMJ evidence-based medicine}, volume = {28}, number = {5}, pages = {295-298}, pmid = {37491142}, issn = {2515-4478}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37490975, year = {2023}, author = {Akbari, A and Hadizadeh, A and Islampanah, M and Salavati Nik, E and Atkin, SL and Sahebkar, A}, title = {COVID-19, G protein-coupled receptor, and renin-angiotensin system autoantibodies: Systematic review and meta-analysis.}, journal = {Autoimmunity reviews}, volume = {22}, number = {9}, pages = {103402}, doi = {10.1016/j.autrev.2023.103402}, pmid = {37490975}, issn = {1873-0183}, mesh = {Humans ; *Renin-Angiotensin System ; Autoantibodies ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Receptors, G-Protein-Coupled ; }, abstract = {INTRODUCTION: There are an increasing number of reports of autoantibodies (AAbs) against host proteins such as G-protein coupled receptors (GPCRs) and the renin-angiotensin system (RAS) in COVID-19 disease. Here we have undertaken a systematic review and meta-analysis of all reports of AAbs against GPCRs and RAS in COVID-19 patients including those with long-COVID or post-COVID symptoms.

METHODS: PubMed, Embase, Web of Science, and Scopus databases were searched to find papers on the role of GPCR and RAS AAbs in the presence and severity of COVID-19 or post- COVID symptoms available through March 21, 2023. Data on the prevalence of AngII or ACE, comparing AngII or ACE between COVID-19 and non-COVID-19, or comparing AngII or ACE between COVID-19 patients with different disease stages were pooled and a meta-analysed using random- or fixed-effects models were undertaken.

RESULTS: The search yielded a total of 1042 articles, of which 68 studies were included in this systematic review and nine in the meta-analysis. Among 18 studies that investigated GPCRs and COVID-19 severity, 18 distinct AAbs were detected. In addition, nine AAbs were found in case reports that assessed post- COVID, and 19 AAbs were found in other studies that assessed post- COVID or long- COVID symptoms. Meta-analysis revealed a significantly higher number of seropositive ACE2 AAbs in COVID-19 patients (odds ratio = 7.766 [2.056, 29.208], p = 0.002) and particularly in severe disease (odds ratio = 11.49 [1.04, 126.86], p = 0.046), whereas AngII-AAbs seropositivity was no different between COVID-19 and control subjects (odds ratio = 2.890 [0.546-15.283], p = 0.21).

CONCLUSIONS: GPCR and RAS AAbs may play an important role in COVID-19 severity, the development of disease progression, long-term symptoms COVID and post- COVID symptoms.}, } @article {pmid37490948, year = {2025}, author = {Hayes, LD and Sanal-Hayes, NEM and Mclaughlin, M and Berry, ECJ and Sculthorpe, NF}, title = {People with Long Covid and ME/CFS Exhibit Similarly Impaired Balance and Physical Capacity: A Case-Case-Control Study.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {140-147}, doi = {10.1016/j.amjmed.2023.06.028}, pmid = {37490948}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; *Postural Balance ; Case-Control Studies ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Fatigue Syndrome, Chronic/physiopathology ; Post-Acute COVID-19 Syndrome ; Adult ; SARS-CoV-2 ; }, abstract = {PURPOSE: Postural sway and physical capacity had not previously been compared between people with long COVID and people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Therefore, this study determined postural sway and physical capacity in people with long COVID (∼16-month illness duration; n = 21) and ME/CFS (∼16-year illness duration; n = 20), vs age-matched healthy controls (n = 20).

METHODS: Postural sway was during a 30-s static stand test. Physical capacity was determined using the Timed Up and Go test and 5 Times Sit to Stand test. Throughout, participants wore isoinertial measurement units.

RESULTS: Postural sway was worse (ie, greater) in people with long COVID and ME/CFS than controls, but not different between long COVID and ME/CFS. Performance of the Timed Up and Go test and 5 Times Sit to Stand test were worse in long COVID and ME/CFS than controls, but not different between long COVID and ME/CFS. Of long COVID and ME/CFS participants, 87% and 13% exceeded the threshold for muscle weakness in the 5 Times Sit to Stand test and Timed Up and Go test, respectively.

CONCLUSIONS: These data suggest that both people with long COVID and people with ME/CFS have similarly impaired balance and physical capacity. Therefore, there is an urgent need for interventions to target postural sway and physical capacity in people with ME/CFS, and given the current pandemic, people with long COVID.}, } @article {pmid37490523, year = {2023}, author = {Huynh, Q and Wexler, N and Smith, J and Wright, L and Ho, F and Allwood, R and Sata, Y and Manca, S and Howden, E and Marwick, TH}, title = {Associations between symptoms and functional capacity in patients after COVID-19 infection and community controls.}, journal = {Internal medicine journal}, volume = {53}, number = {9}, pages = {1540-1547}, pmid = {37490523}, issn = {1445-5994}, support = {105282/WT_/Wellcome Trust/United Kingdom ; 105282/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; Male ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19 ; Exercise Test ; Exercise ; Exercise Tolerance ; }, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC or 'long COVID') reflect ongoing symptoms, but these are non-specific and common in the wider community. Few reports of PASC have been compared with a control group.

AIMS: To compare symptoms and objective impairment of functional capacity in patients with previous COVID-19 infection with uninfected community controls.

METHODS: In this community-based, cross-sectional study of functional capacity, 562 patients from Western Melbourne who had recovered from COVID-19 infections in 2021 and 2022 were compared with controls from the same community and tested for functional capacity pre-COVID-19. Functional impairment (<85% of the predicted response) was assessed using the Duke Activity Status Index (DASI) and 6-min walk distance (6MWD) test. A subgroup underwent cardiopulmonary exercise testing before and after exercise training.

RESULTS: Of 562 respondents (age 54 ± 12 years, 69% women), 389 were symptomatic. Functional impairment (<85% predicted metabolic equivalent of tasks) was documented by DASI in 149 participants (27%), and abnormal 6MWD (<85% predicted) was observed in 14% of the symptomatic participants. Despite fewer risk factors and younger age, patients with COVID-19 had lower functional capacity by 6MWD (P < 0.001) and more depression (P < 0.001) than controls. In a pilot group of seven participants (age 58 ± 12 years, two women, VO2 18.9 ± 5.7 mL/kg/min), repeat testing after exercise training showed a 20% increase in peak workload.

CONCLUSIONS: Although most participants (69%) had symptoms consistent with long COVID, significant subjective functional impairment was documented in 27% and objective functional impairment in 14%. An exercise training programme might be beneficial for appropriately selected patients.}, } @article {pmid37490472, year = {2023}, author = {Strasser, ZH and Dagliati, A and Shakeri Hossein Abad, Z and Klann, JG and Wagholikar, KB and Mesa, R and Visweswaran, S and Morris, M and Luo, Y and Henderson, DW and Samayamuthu, MJ and , and Omenn, GS and Xia, Z and Holmes, JH and Estiri, H and Murphy, SN}, title = {A retrospective cohort analysis leveraging augmented intelligence to characterize long COVID in the electronic health record: A precision medicine framework.}, journal = {PLOS digital health}, volume = {2}, number = {7}, pages = {e0000301}, pmid = {37490472}, issn = {2767-3170}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; R01 AI165535/AI/NIAID NIH HHS/United States ; R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, abstract = {Physical and psychological symptoms lasting months following an acute COVID-19 infection are now recognized as post-acute sequelae of COVID-19 (PASC). Accurate tools for identifying such patients could enhance screening capabilities for the recruitment for clinical trials, improve the reliability of disease estimates, and allow for more accurate downstream cohort analysis. In this retrospective cohort study, we analyzed the EHR of hospitalized COVID-19 patients across three healthcare systems to develop a pipeline for better identifying patients with persistent PASC symptoms (dyspnea, fatigue, or joint pain) after their SARS-CoV-2 infection. We implemented distributed representation learning powered by the Machine Learning for modeling Health Outcomes (MLHO) to identify novel EHR features that could suggest PASC symptoms outside of typical diagnosis codes. MLHO applies an entropy-based feature selection and boosting algorithms for representation mining. These improved definitions were then used for estimating PASC among hospitalized patients. 30,422 hospitalized patients were diagnosed with COVID-19 across three healthcare systems between March 13, 2020 and February 28, 2021. The mean age of the population was 62.3 years (SD, 21.0 years) and 15,124 (49.7%) were female. We implemented the distributed representation learning technique to augment PASC definitions. These definitions were found to have positive predictive values of 0.73, 0.74, and 0.91 for dyspnea, fatigue, and joint pain, respectively. We estimated that 25 percent (CI 95%: 6-48), 11 percent (CI 95%: 6-15), and 13 percent (CI 95%: 8-17) of hospitalized COVID-19 patients will have dyspnea, fatigue, and joint pain, respectively, 3 months or longer after a COVID-19 diagnosis. We present a validated framework for screening and identifying patients with PASC in the EHR and then use the tool to estimate its prevalence among hospitalized COVID-19 patients.}, } @article {pmid37490194, year = {2023}, author = {Gonzalez-Fernandez, E and Huang, J}, title = {Cognitive Aspects of COVID-19.}, journal = {Current neurology and neuroscience reports}, volume = {23}, number = {9}, pages = {531-538}, pmid = {37490194}, issn = {1534-6293}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Alzheimer Disease/complications/epidemiology ; *Cognitive Dysfunction/epidemiology/etiology ; Cognition ; }, abstract = {PURPOSE OF REVIEW: Since the beginning of the coronavirus disease 2019 pandemic, many lasting neurological sequelae including cognitive impairment have been recognized as part of the so-called long COVID syndrome. This narrative review summarizes the cognitive aspects of COVID-19.

RECENT FINDINGS: Studies have consistently identified attention, memory, and executive functions as the cognitive domains most often affected by COVID-19 infection. Many studies have also reported neuroimaging, biofluid, and neurophysiological abnormalities that could potentially reflect the pathophysiological aspects of post-COVID cognitive impairment. While patients suffering from dementia have an elevated risk of COVID-19 infection, increasing evidence has also indicated that COVID-19 infection may increase the risks of Alzheimer's disease, suggesting bidirectional relationships. Post-COVID cognitive dysfunction is a pervasive and multifaceted problem and we are surely in our infancy of understanding. Future elucidation into the long-term effects, mechanisms, and therapies will depend on a concerted effort from clinicians, researchers, patients, and policy-makers alike.}, } @article {pmid37489469, year = {2023}, author = {Bellini, D and Capodiferro, P and Vicini, S and Rengo, M and Carbone, I}, title = {Long COVID in Young Patients: Impact on Lung Volume Evaluated Using Multidetector CT.}, journal = {Tomography (Ann Arbor, Mich.)}, volume = {9}, number = {4}, pages = {1276-1285}, pmid = {37489469}, issn = {2379-139X}, mesh = {Humans ; Adult ; Adolescent ; Young Adult ; *COVID-19/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Retrospective Studies ; Tomography, X-Ray Computed/methods ; Lung Volume Measurements ; }, abstract = {PURPOSE: To evaluate using quantitative analysis on chest CT images a possible lung volume reduction in Long COVID patients who complain mild respiratory symptoms, with chest CT negative for inflammatory findings.

MATERIALS AND METHODS: CT images of patients from 18 to 40 years old who underwent chest CT scan at our institution were analyzed retrospectively, using AwServer Thoracic VCAR software for a quantitative study. Exclusion criteria were inflammatory findings at CT, previous lung surgery, lung cancer, and breath artifacts that invalidate the quality of images. Patients were divided into two groups: in the first one ("post-COVID") were patients who had previous SARS-CoV-2 infection, confirmed by an RT-PCR, who underwent chest CT from 3 to 6 months after their negativization for long COVID symptoms; in the control group ("non-COVID"), were enrolled patients who underwent a chest CT scan from January 2018 to December 2019, before the spread of COVID in Italy.

RESULTS: Our final population included 154 TC, 77 post-COVID patients (mean age 33 ± 6) and 77 non-COVID patients (mean age 33 ± 4.9). Non statistical significative differences were obtained between groups in terms of age, sex, and other characteristics that affect total lung capacity such as obesity, thoracic malformations, and smoking habit. Mean values of the total lung volume (TV), right-lung volume (RV), and left-lung volume (LV) in the post-COVID group compared with non-COVID group were, respectively: 5.25 ± 0.25 L vs. 5.72 ± 0.26 L (p = 0.01); 2.76 ± 0.14 L vs. 3 ± 0.14 L (p = 0.01); 2.48 ± 0.12 L vs. 2.72 ± 0.12 L (p = 0.01).

CONCLUSION: In patients with symptoms suggesting Long COVID and negative chest CT macroscopic findings, quantitative volume analysis demonstrated a mean value of reduction in lung volume of 10% compared to patients of the same age who never had COVID. A chest CT negative for inflammatory findings may induce clinicians to attribute Long COVID mild respiratory symptoms to anxiety, especially in young patients. Our study brings us beyond appearances and beyond the classic radiological signs, introducing a quantitative evaluation of lung volumes in these patients. It is hard to establish to what extent this finding may contribute to Long COVID symptoms, but this is another step to gain a wider knowledge of the potential long-term effects caused by this new virus.}, } @article {pmid37489358, year = {2023}, author = {Reiss, AB and Greene, C and Dayaramani, C and Rauchman, SH and Stecker, MM and De Leon, J and Pinkhasov, A}, title = {Long COVID, the Brain, Nerves, and Cognitive Function.}, journal = {Neurology international}, volume = {15}, number = {3}, pages = {821-841}, pmid = {37489358}, issn = {2035-8385}, abstract = {SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored.}, } @article {pmid37488409, year = {2023}, author = {Herczeg, V and Garai, R and Takács, J and Kovács, F and Luczay, A and Hrapka, E and Krivácsy, P and Hosszú, É and Beniczky, NJ and Németh, Á and Szilágyi, ES and Pécsi, A and Szabó, Z and Szabó, AJ and Tóth-Heyn, P}, title = {Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis.}, journal = {European journal of pediatrics}, volume = {182}, number = {10}, pages = {4443-4455}, pmid = {37488409}, issn = {1432-1076}, mesh = {Adult ; Child ; Humans ; Male ; Female ; *Thyroiditis, Autoimmune/complications/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; COVID-19 Vaccines/adverse effects ; *COVID-19/epidemiology/prevention & control/complications ; SARS-CoV-2 ; Vaccination/adverse effects ; Thyrotropin ; }, abstract = {Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24[th] March, 2021 to 23[rd] March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ[2](1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations. Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening. What is Known: • Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances. • Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found. What is New: • TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome. • We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.}, } @article {pmid37488240, year = {2023}, author = {Kim, Y and Bae, S and Chang, HH and Kim, SW}, title = {Author Correction: Long COVID prevalence and impact on quality of life 2 years after acute COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11960}, doi = {10.1038/s41598-023-39132-3}, pmid = {37488240}, issn = {2045-2322}, } @article {pmid37487957, year = {2024}, author = {Maccarone, MC and Coraci, D and Regazzo, G and Sarandria, N and Scanu, A and Masiero, S}, title = {Evolution of musculoskeletal symptoms in Long COVID syndrome: a lexical analysis to approach requirements for an interdisciplinary management.}, journal = {Joint bone spine}, volume = {91}, number = {1}, pages = {105623}, doi = {10.1016/j.jbspin.2023.105623}, pmid = {37487957}, issn = {1778-7254}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; Arthralgia ; }, abstract = {Long COVID syndrome is characterized by new, returning, or persistent symptoms after the initial SARS-CoV-2 infection. Among the potential long-term effects of COVID-19, several different musculoskeletal symptoms have been reported in many patients with an important impact on quality of life. The rehabilitation needs of Long COVID patients could be dynamic. However, to date there are no studies that have evaluated how the rehabilitation needs of patients with Long COVID syndrome have changed over time. We conducted a literature review to summarize the most recurrent manifestations of the Long COVID syndrome during the three years of the pandemic, as well as the evolution of musculoskeletal symptoms, through lexical analysis. This approach allowed us to investigate the literature, highlighting how the most used words to describe Long COVID symptoms and outcomes have changed over different periods. Our analysis showed an increasing involvement of the musculoskeletal system in Long COVID symptomatology, as evidenced by the progressive growth of fatigue and weakness symptoms over time. In addition, arthralgia has always been associated with Long COVID. The lexical analysis we conducted emphasizes the need for interdisciplinary management, as the symptoms reported are interconnected. Moreover, this novel approach highlights that the Long COVID syndrome can be interpreted as a dynamic entity requiring up-to-date rehabilitative interventions. The worldwide healthcare systems should be founded on multidisciplinary teams to guarantee early and comprehensive rehabilitation to reduce the socio-sanitary burden associated with this syndrome.}, } @article {pmid37486805, year = {2023}, author = {Badawy, AA}, title = {The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy.}, journal = {Bioscience reports}, volume = {43}, number = {8}, pages = {}, pmid = {37486805}, issn = {1573-4935}, mesh = {Humans ; *Kynurenine/metabolism ; Tryptophan/metabolism ; Poly(ADP-ribose) Polymerase Inhibitors ; NAD ; *COVID-19/therapy ; SARS-CoV-2/metabolism ; Immunotherapy ; }, abstract = {SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is the main source of the vital cellular effector NAD+ and intermediate metabolites that modulate immune and neuronal functions. Trp metabolism is the top pathway influenced by COVID-19. Sixteen studies established virus-induced activation of the KP mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO1) in most affected tissues and of IDO2 in lung by the increased release of proinflammatory cytokines but could additionally involve increased flux of plasma free Trp and induction of Trp 2,3-dioxygenase (TDO) by cortisol. The major Kyn metabolite targeted by COVID-19 is kynurenic acid (KA), the Kyn metabolite with the greatest affinity for the aryl hydrocarbon receptor (AhR), which is also activated by COVID-19. AhR activation initiates two important series of events: a vicious circle involving IDO1 induction, KA accumulation and further AhR activation, and activation of poly (ADP-ribose) polymerase (PARP) leading to NAD+ depletion and cell death. The virus further deprives the host of NAD+ by inhibiting its main biosynthetic pathway from quinolinic acid, while simultaneously acquiring NAD+ by promoting its synthesis from nicotinamide in the salvage pathway. Additionally, the protective effects of sirtuin 1 are minimised by the PARP activation. KP dysfunction may also underpin the mood and neurological disorders acutely and during 'long COVID'. More studies of potential effects of vaccination therapy on the KP are required and exploration of therapeutic strategies involving modulation of the KP changes are proposed.}, } @article {pmid37486567, year = {2023}, author = {Di Fusco, M and Sun, X and Moran, MM and Coetzer, H and Zamparo, JM and Alvarez, MB and Puzniak, L and Tabak, YP and Cappelleri, JC}, title = {Impact of COVID-19 and effects of booster vaccination with BNT162b2 on six-month long COVID symptoms, quality of life, work productivity and activity impairment during Omicron.}, journal = {Journal of patient-reported outcomes}, volume = {7}, number = {1}, pages = {77}, pmid = {37486567}, issn = {2509-8020}, mesh = {Female ; Humans ; Adult ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; BNT162 Vaccine ; Quality of Life ; SARS-CoV-2 ; Vaccination ; }, abstract = {BACKGROUND: Longitudinal estimates of long COVID burden during Omicron remain limited. This study characterized long-term impacts of COVID-19 and booster vaccination on symptoms, Health-Related Quality of Life (HRQoL), and Work Productivity Activity Impairment (WPAI).

METHODS: Outpatients with ≥ 1 self-reported symptom and positive SARS-CoV-2 test at CVS Health United States test sites were recruited between 01/31 and 04/30/2022. Symptoms, EQ-5D and WPAI were collected via online surveys until 6 months following infection. Both observed and model-based estimates were analyzed. Effect sizes based on Cohen's d quantified the magnitude of outcome changes over time, within and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for covariates. Logistic regression assessed odds ratio (OR) of long COVID between vaccination groups.

RESULTS: At long COVID start (Week 4), 328 participants included 87 (27%) Boosted with BNT162b2, 86 (26%) with a BNT162b2 primary series (Primed), and 155 (47%) Unvaccinated. Mean age was 42.0 years, 73.8% were female, 26.5% had ≥ 1 comorbidity, 36.9% prior infection, and 39.6% reported ≥ 3 symptoms (mean: 3.1 symptoms). At Month 6, among 260 participants, Boosted reported a mean of 1.1 symptoms versus 3.4 and 2.8 in Unvaccinated and Primed, respectively (p < 0.001). Boosted had reduced risks of ≥ 3 symptoms versus Unvaccinated (observed: OR 0.22, 95% CI 0.10-0.47, p < 0.001; model-based: OR 0.36, 95% CI 0.15-0.87, p = 0.019) and Primed (observed: OR 0.29, 95% CI 0.13-0.67, p = 0.003; model-based: OR 0.59, 95% CI 0.21-1.65, p = 0.459). Results were consistent using ≥ 2 symptoms. Regarding HRQoL, among those with long COVID, Boosted had higher EQ-5D Utility Index (UI) than Unvaccinated (observed: 0.922 vs. 0.731, p = 0.014; model-based: 0.910 vs. 0.758, p-value = 0.038) and Primed (0.922 vs. 0.648, p = 0.014; model-based: 0.910 vs. 0.708, p-value = 0.008). Observed and model-based estimates for EQ-VAS and UI among Boosted were comparable with pre-COVID since Month 3. Subjects vaccinated generally reported better WPAI scores.

CONCLUSIONS: Long COVID negatively impacted HRQoL and WPAI. The BNT162b2 booster could have a beneficial effect in reducing the risk and burden of long COVID. Boosted participants reported fewer and less durable symptoms, which contributed to improve HRQoL and maintain WPAI levels. Limitations included self-reported data and small sample size for WPAI.}, } @article {pmid37486510, year = {2024}, author = {Cadore, NA and Lord, VO and Recamonde-Mendoza, M and Kowalski, TW and Vianna, FSL}, title = {Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection.}, journal = {Biochemical genetics}, volume = {62}, number = {2}, pages = {892-914}, pmid = {37486510}, issn = {1573-4927}, support = {88887.518451/2020-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 150181/2023-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Humans ; Autopsy ; Axonemal Dyneins/metabolism ; *COVID-19/genetics/metabolism/pathology ; Gene Expression Profiling ; Lung/metabolism/pathology ; Post-Acute COVID-19 Syndrome ; *Pulmonary Fibrosis/metabolism/pathology ; SARS-CoV-2/metabolism ; Transcriptome ; }, abstract = {Severe COVID-19 is a systemic disorder involving excessive inflammatory response, metabolic dysfunction, multi-organ damage, and several clinical features. Here, we performed a transcriptome meta-analysis investigating genes and molecular mechanisms related to COVID-19 severity and outcomes. First, transcriptomic data of cellular models of SARS-CoV-2 infection were compiled to understand the first response to the infection. Then, transcriptomic data from lung autopsies of patients deceased due to COVID-19 were compiled to analyze altered genes of damaged lung tissue. These analyses were followed by functional enrichment analyses and gene-phenotype association. A biological network was constructed using the disturbed genes in the lung autopsy meta-analysis. Central genes were defined considering closeness and betweenness centrality degrees. A sub-network phenotype-gene interaction analysis was performed. The meta-analysis of cellular models found genes mainly associated with cytokine signaling and other pathogen response pathways. The meta-analysis of lung autopsy tissue found genes associated with coagulopathy, lung fibrosis, multi-organ damage, and long COVID-19. Only genes DNAH9 and FAM216B were found perturbed in both meta-analyses. BLNK, FABP4, GRIA1, ATF3, TREM2, TPPP, TPPP3, FOS, ALB, JUNB, LMNA, ADRB2, PPARG, TNNC1, and EGR1 were identified as central elements among perturbed genes in lung autopsy and were found associated with several clinical features of severe COVID-19. Central elements were suggested as interesting targets to investigate the relation with features of COVID-19 severity, such as coagulopathy, lung fibrosis, and organ damage.}, } @article {pmid37485778, year = {2024}, author = {Feldman, DE and Mazer, B}, title = {Long COVID in Persons With Self-Reported Arthritis: Symptoms, Associated Factors, and Functional Limitations.}, journal = {Arthritis care & research}, volume = {76}, number = {1}, pages = {57-62}, doi = {10.1002/acr.25200}, pmid = {37485778}, issn = {2151-4658}, support = {//Fondation Cité de la Santé/ ; //Jewish Rehabilitation Hospital Foundation/ ; }, mesh = {Humans ; Female ; Male ; Self Report ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; COVID-19 Testing ; *Arthritis ; }, abstract = {OBJECTIVE: The aim is to describe both long COVID symptoms and associated factors in a cohort of individuals with a self-reported history of arthritis as well as change in function in persons with arthritis and long COVID compared to pre-COVID status.

METHODS: Among 2,764 persons with a confirmed COVID-19 diagnosis who responded to an online survey at least 12 weeks post-infection, 171 reported a history of arthritis and formed our study sample. We calculated the frequency of long COVID defined as troubled by persistent symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression. Among those with long COVID, we describe limitations in activity and function in comparison to pre-COVID status.

RESULTS: In our sample, 53.5% (n = 91) reported being troubled by ongoing symptoms at the time of completing the questionnaire (long COVID), with the most frequent symptoms as the following: fatigue, myalgia, weakness, breathlessness, low mood, anxiety, and sleep disturbance. Factors associated with long COVID were female sex, having been hospitalized for COVID, and having at least 1 other chronic disease. Persons with long COVID had substantial declines in function, notably in global health status, usual activities, mobility, personal care, and employment status. Also, 37% of those with long COVID reported moderate to severe increase in pain.

CONCLUSION: Persons with arthritis who have long COVID have substantial limitations in function compared to their pre-COVID status. There is a need to implement effective interventions to improve functional status in persons with arthritis and long COVID.}, } @article {pmid37485412, year = {2023}, author = {Nongpiur, A and Barman, B and Syiem, K and Mawiong, AM and Anand, N and Nune, A}, title = {A cross-sectional study of the mental health burden among COVID-19 survivors.}, journal = {Indian journal of psychiatry}, volume = {65}, number = {6}, pages = {661-666}, pmid = {37485412}, issn = {0019-5545}, abstract = {INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on mental health, including stress, anxiety, and depression. This study aimed to assess the incidence and severity of mental health issues among individuals diagnosed with COVID-19 infection.

METHODS: A semi-structured proforma for socio-demographic and clinical parameters was used to collect cross-sectional hospital-based data of subjects who tested positive for COVID-19 infection. The Modified Fatigue Impact Scale (MFIS), Hospital Anxiety and Depression Scale (HADS), and Perceived Stress Scale (PSS) were used to assess the presence of physical, psychological, and cognitive symptoms. The presence of anxiety, depression, and stress was based on the cut-off scores for HADS-A (≥8), HADS-D (≥8), and PSS (≥14), respectively.

RESULTS: A total of 101 patients comprising 39 (38.6%) males were recruited. Compared to nuclear families, we observed that patients living in joint families had significantly greater severity scores for fatigue [MFIS (p = 0.04)], anxiety [HADS-A (p = 0.004)], depression [HADS-D (p = 0.004)], and stress [PSS (p = 0.02)]. Based on the cut-off scores, we found that 44 (43.6%) patient had anxiety, 41 (40.6%) had depressive, and 72 (71.3%) had moderate to high stress symptoms, respectively. We also observed significantly greater fatigue and anxiety scores, that is, MFIS (p = 0.008) and HADS-A (p = 0.03) in those who received oxygen therapy compared to those who did not. The subjects who received corticosteroids were older (p = 0.01) and had significantly higher stress scores [PSS (p < 0.001)]. The study showed that patients who were assessed more than 3 months post-COVID-19 infection had higher fatigue and depression scores; however, the difference did not reach statistical significance (MFIS P = 0.058; HADS P = 0.059).

CONCLUSION: Our study confirms that COVID-19 infection can cause various adverse mental health issues. Mitigating the hazardous effects of COVID-19 pandemic on mental health should be a top priority for public health to prevent long-term complications.}, } @article {pmid37485095, year = {2023}, author = {Gujral, HS and Sahasrabudhe, TR and Nirmala, MA}, title = {A Systematic Evaluation of Risk Predictors for COVID-19 Sequelae.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e40717}, pmid = {37485095}, issn = {2168-8184}, abstract = {Background Multisystem involvement in coronavirus disease 2019 (COVID-19) is known since the beginning of the pandemic, and post-COVID-19 sequelae have often been reported. The term 'long Covid' encompasses these signs and symptoms. The aim of our study was to study different after-effects which patients endured within 12 months after recovery from acute COVID-19 and to study the various risk predictors. Methods This was a longitudinal observational study of a cohort of 146 patients who recovered from COVID-19 illness. Patients were enrolled during the first four weeks of the onset of their illness, and a monthly follow-up assessment was done for six months that included a detailed history of persistent or new symptoms, new illnesses diagnosed, and complete biochemical, pulmonary, cardiac, neurological and psychiatric evaluation, both objective and subjective. A final follow-up was also done at the end of one year of enrolment. Based on the patient's self-reported history and our multi-system assessment, recorded sequelae were classified according to the involved organ system. These were correlated with possible risk predictors and statistically significant associations were established. Results One hundred and twenty subjects out of 146 total subjects qualified for final analysis. Pulmonary sequelae (48/120; 40%) were the most followed by psychiatric (30/120; 25%), neurological (26/120; 21.7%), and opportunistic infections (7/120; 5.8%). A total of 39/120 (32.1%) cases complained of prolonged dyspnoea. Six out of 120 i.e. 5% of study participants had new-onset diabetes. Twenty-six out of 120 (21.7%) had radiological signs of pulmonary fibrosis. Patients with co-morbidities, older age, higher body mass index, and patients with severe disease were found to be at higher risk of developing these sequelae. Poor nutrition, female gender, and hospitalization were predictors of psychiatric sequelae. Diabetes and liberal steroid use during COVID-19 management were predictors of opportunistic fungal infections. Conclusion This study evaluated post-COVID-19 sequalae in-depth both objectively and subjectively. Some specific predictors for specific sequelae were confirmed on statistical correlation. Long-term follow-up of high-risk persons is therefore recommended after the cure of COVID-19.}, } @article {pmid37481021, year = {2025}, author = {Mclaughlin, M and Cerexhe, L and Macdonald, E and Ingram, J and Sanal-Hayes, NEM and Meach, R and Carless, D and Sculthorpe, N}, title = {A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long COVID in Scotland: Part I.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {121-130}, doi = {10.1016/j.amjmed.2023.07.004}, pmid = {37481021}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; Scotland/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology/complications ; Prevalence ; *Severity of Illness Index ; Adult ; Aged ; *Post-Acute COVID-19 Syndrome ; Activities of Daily Living ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Commonly reported symptoms of long COVID may have different patterns of prevalence and presentation across different countries. While some limited data have been reported for the United Kingdom, national specificity for Scotland is less clear. We present a cross-sectional survey to examine the symptom prevalence, frequency, and severity of long COVID for people living with the condition in Scotland.

METHODS: An online survey was created in the English language and was available between April 21, 2022 and August 5, 2022. Participants were included if they were ≥18 years old, living in Scotland, and had self-diagnosed or confirmed long COVID; and excluded if they were hospitalized during their initial infection. Within this article we quantify symptom prevalence, frequency, severity, and duration.

RESULTS: Participants (n = 253) reported the most prevalent long-COVID symptoms to be post-exertional malaise (95%), fatigue/tiredness (85%), and cognitive impairment (68%). Fatigue/tiredness, problems with activities of daily living (ADL), and general pain were most frequently occurring, while sleep difficulties, problems with ADL, and nausea were the most severe. Scottish Index of Multiple Deprivation associated with symptom number, severity, and frequency, whereas vaccine status, age, sex, and smoking status had limited or no association.

CONCLUSIONS: These findings outline the challenges faced for those living with long COVID and highlight the need for longitudinal research to ascertain a better understanding of the condition and its longer-term societal impact.}, } @article {pmid37480937, year = {2023}, author = {The Lancet Respiratory Medicine, }, title = {Long COVID: confronting a growing public health crisis.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {663}, doi = {10.1016/S2213-2600(23)00268-0}, pmid = {37480937}, issn = {2213-2619}, mesh = {Humans ; *Public Health ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37480344, year = {2023}, author = {Pozzi, C and Sarti, R and Levi, R and Mollura, M and Azzolini, E and Barbieri, R and Mantovani, A and Rescigno, M}, title = {Association Between Duration of SARS-CoV-2 Positivity and Long COVID.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {11}, pages = {1531-1533}, pmid = {37480344}, issn = {1537-6591}, support = {//Italian Ministry of Health/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; BNT162 Vaccine ; Disease Progression ; }, abstract = {In an observational study, we analyzed 1293 healthcare workers previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 34.1% developed postacute sequelae of SARS-CoV-2 infection (also known as long COVID). Using a multivariate logistic regression model, we demonstrate that the likelihood of developing long COVID in infected individuals rises with the increasing of duration of infection and that 3 doses of the BNT162b2 vaccine are protective, even during the Omicron wave.}, } @article {pmid37479879, year = {2023}, author = {Freund, O and Breslavsky, A and Fried, S and Givoli-Vilensky, R and Cohen-Rubin, S and Zacks, N and Kleinhendler, E and Unterman, A and Frydman, S and Wand, O and Bilenko, N and Bar-Shai, A}, title = {Interactions and clinical implications of serological and respiratory variables 3 months after acute COVID-19.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {7}, pages = {3729-3736}, pmid = {37479879}, issn = {1591-9528}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Cohort Studies ; Antibodies, Neutralizing ; Antibodies, Viral ; }, abstract = {Medical follow-up of symptomatic patients after acute Coronavirus Disease 2019 (COVID-19) results in major burdens on patients and healthcare systems. The value of serological markers as part of this follow-up remains undetermined. We aimed to evaluate the clinical implications of serological markers for follow-up of acute COVID-19. For this purpose, we conducted an observational cohort study of patients 3 months after acute COVID-19. Participants visited a respiratory-clinic between October 2020 and March 2021, and completed pulmonary function tests (PFTs), serological tests, symptom-related questionnaires, and chest CT scans. Overall, 275 patients were included at a median of 82 days (IQR 64-111) post infection. 162 (59%) patients had diffusing capacity for carbon monoxide corrected for hemoglobin (DLCOc) below 80%, and 69 (25%) had bilateral chest abnormalities on CT scan. In multivariate analysis, anti-S levels were an independent predictor for DLCOc (β = - 0.14, p = 0.036). Anti-S levels were also associated with severe COVID-19 and older age, and correlated with anti-nucleocapsid (r = 0.30, p < 0.001) and antibodies to receptor binding domain (RBD, r = 0.37, p < 0.001). Other serological variables were not associated with clinical outcomes. In conclusion, symptomatic patients 3-months after COVID-19 had high respiratory symptomatic burden, in which anti-S levels were significantly associated with previous severe COVID-19 and DLCOc.}, } @article {pmid37479120, year = {2023}, author = {Freund, O and Breslavsky, A and Givoli-Vilensky, R and Zacks, N and Gershman, E and Melloul, A and Wand, O and Bilenko, N and Bar-Shai, A}, title = {Assessment of a close respiratory follow-up schedule at 3 and 6 months after acute COVID-19 and its related investigations.}, journal = {Respiratory medicine}, volume = {217}, number = {}, pages = {107367}, doi = {10.1016/j.rmed.2023.107367}, pmid = {37479120}, issn = {1532-3064}, mesh = {Adult ; Humans ; Middle Aged ; Aged ; *COVID-19/epidemiology ; SARS-CoV-2 ; Follow-Up Studies ; Prospective Studies ; Lung ; }, abstract = {BACKGROUND: Respiratory sequela after acute COVID-19 is common and requires medical follow-up. Considering its vast economic impact, there is still no consensus regarding the mid-term follow-up plan after recovery.

OBJECTIVE: To evaluate the necessity of a close pulmonary follow-up schedule after acute COVID-19 and its related investigations.

METHODS: A prospective cohort study including adult patients after acute COVID-19 pneumonia. Patients were invited or referred to a 3- and 6-month follow-up visits at a large pulmonary institute in a tertiary center. Before each visit, patients completed demographic and clinical questionnaires, pulmonary function tests (PFTs), and chest CT scans.

RESULTS: 168 patients were included after completing both visits (medians of 80 and 177 days). Their mean age was 58 ± 15 and 52% recovered from severe or critical COVID-19. Between the two visits, there was no change in DLCOc (mean 73 ± 18 %predicted in both visits) and FVC (mean 90 ± 16 vs. 89 ± 16 %predicted). The COPD assessment tool and modified Medical Research Council scale had inverse correlations with the DLCOc, and similarly did not change between the visits. Occupational exposures were the only factor associated with a change in DLCOc during follow-up (3% decrease, p = 0.04). An improvement in chest CT findings at the second visit was not associated with a change in PFTs.

CONCLUSIONS: Most clinical variables did not change during a close follow-up schedule in the first six months after acute COVID-19. Such a follow-up plan does not appear necessary and should be personalized to limit excessive costs and resources.}, } @article {pmid37478960, year = {2023}, author = {Mclaughlin, M and Cerexhe, L and Macdonald, E and Ingram, J and Sanal-Hayes, NEM and Hayes, LD and Meach, R and Carless, D and Sculthorpe, N}, title = {A Cross-Sectional Study of Symptom Prevalence, Frequency, Severity, and Impact of Long COVID in Scotland: Part II.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2023.07.009}, pmid = {37478960}, issn = {1555-7162}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {BACKGROUND: There has been some effort to map the prevalence, frequency, and severity of symptoms of long COVID at local and national levels. However, what is frequently absent from such accounts is details of the impact the disease and its symptoms have had on those living with the condition. In this article, we present details of the impact on work, caring, and mental health gathered using a cross-sectional survey.

METHODS: Data were collected using an online survey that was available from April 21, 2022, to August 5, 2022. Included participants had either self-diagnosed or confirmed long COVID, were living in Scotland, and were aged ≥18 years. Hospitalization during initial COVID-19 infection was an exclusion criterion. Participants were asked to report on the impact of their illness on everyday activities such as working, studying, or caring. They also completed an assessment of their current mood.

RESULTS: People with long COVID were often severely impacted in their ability to work and study. Severe impact on work and study were predicted by more severe and more frequent fatigue, more severe pain, and more severe cognitive impairment. Respondents' ability to care for child dependents was also associated with more severe and more frequent fatigue, and more severe cognitive impairments. More severe pain associated with greater impact on adult care. Negative mood correlated most strongly with frequency and severity of neurological symptoms, including lack of attention, loss of smell, impaired sense of smell, loss of taste, impaired sense of taste, and loss of appetite.

CONCLUSIONS: Long COVID has a significant impact on ability to work, study, and care for dependents. The severity of this impact is associated with specific symptom burden, including fatigue, pain, and cognitive impairment.}, } @article {pmid37478918, year = {2023}, author = {Bowden-Reid, E and Ledger, S and Zhang, Y and Di Giallonardo, F and Aggarwal, A and Stella, AO and Akerman, A and Milogiannakis, V and Walker, G and Rawlinson, W and Turville, S and Kelleher, AD and Ahlenstiel, C}, title = {Novel siRNA therapeutics demonstrate multi-variant efficacy against SARS-CoV-2.}, journal = {Antiviral research}, volume = {217}, number = {}, pages = {105677}, doi = {10.1016/j.antiviral.2023.105677}, pmid = {37478918}, issn = {1872-9096}, mesh = {Animals ; Humans ; RNA, Small Interfering/genetics ; SARS-CoV-2/genetics ; Antiviral Agents/pharmacology/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19/therapy ; *Hepatitis C, Chronic ; Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus that causes COVID-19 disease, with an estimated global mortality of approximately 2%. While global response strategies, which are predominantly reliant on regular vaccinations, have shifted from zero COVID to living with COVID, there is a distinct lack of broad-spectrum direct acting antiviral therapies that maintain efficacy across evolving SARS-CoV-2 variants of concern. This is of most concern for immunocompromised and immunosuppressed individuals who lack robust immune responses following vaccination, and others at risk for severe COVID and long-COVID. RNA interference (RNAi) therapeutics induced by short interfering RNAs (siRNAs) offer a promising antiviral treatment option, with broad-spectrum antiviral capabilities unparalleled by current antiviral therapeutics and a high genetic barrier to antiviral escape. Here we describe novel siRNAs, targeting highly conserved regions of the SARS-CoV-1 and 2 genome of both human and animal species, with multi-variant antiviral potency against eight SARS-CoV-2 lineages - Ancestral VIC01, Alpha, Beta, Gamma, Delta, Zeta, Kappa and Omicron. Treatment with our siRNA resulted in significant protection against virus-mediated cell death in vitro, with >97% cell survival (P < 0.0001), and corresponding reductions of viral nucleocapsid RNA of up to 99.9% (P < 0.0001). When compared to antivirals; Sotrovimab and Remdesivir, the siRNAs demonstrated a more potent antiviral effect and similarly, when multiplexing siRNAs to target different viral regions simultaneously, an increased antiviral effect was observed compared to individual siRNA treatments (P < 0.0001). These results demonstrate the potential for a highly effective broad-spectrum direct acting antiviral against multiple SARS-CoV-2 variants, including variants resistant to antivirals and vaccine generated neutralizing antibodies.}, } @article {pmid37477768, year = {2023}, author = {Tsilioni, I and Theoharides, TC}, title = {Recombinant SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Stimulate Release of Different Pro-Inflammatory Mediators via Activation of Distinct Receptors on Human Microglia Cells.}, journal = {Molecular neurobiology}, volume = {60}, number = {11}, pages = {6704-6714}, pmid = {37477768}, issn = {1559-1182}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism ; Protein Binding ; Angiotensin-Converting Enzyme 2/metabolism ; Post-Acute COVID-19 Syndrome ; Neuroinflammatory Diseases ; Microglia/metabolism ; }, abstract = {SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin converting enzyme 2 (ACE2) on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that SARS-CoV-2 infection produces neuroinflammation associated with neurological, neuropsychiatric, and cognitive symptoms persists well past the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The neuroimmune mechanism(s) involved in long-COVID have not been adequately characterized. In this study, we show that recombinant SARS-CoV-2 full-length S protein stimulates release of pro-inflammatory IL-1b, CXCL8, IL-6, and MMP-9 from cultured human microglia via TLR4 receptor activation. Instead, recombinant receptor-binding domain (RBD) stimulates release of TNF-α, IL-18, and S100B via ACE2 signaling. These results provide evidence that SARS-CoV-2 spike protein contributes to neuroinflammation through different mechanisms that may be involved in CNS pathologies associated with long-COVID.}, } @article {pmid37476923, year = {2023}, author = {Jiang, L and Li, X and Nie, J and Tang, K and Bhutta, ZA}, title = {A Systematic Review of Persistent Clinical Features After SARS-CoV-2 in the Pediatric Population.}, journal = {Pediatrics}, volume = {152}, number = {2}, pages = {}, pmid = {37476923}, issn = {1098-4275}, mesh = {Adolescent ; Child ; Female ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Young Adult ; Adult ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Prospective Studies ; }, abstract = {CONTEXT: Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain.

OBJECTIVE: To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population.

DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 database, google scholar, medRxiv, bioRxiv, and multiple national public health databases.

STUDY SELECTION: Published articles and preprints from December, 2019 to December, 2022 investigating the epidemiology and characteristics of persistent clinical features at least 3 months after COVID-19 in children and adolescents (0-19 years old) were included.

DATA EXTRACTION: Study characteristics and detailed description of long COVID were extracted into a predefined form.

RESULTS: Twenty seven cohorts and 4 cross-sectional studies met the inclusion criteria and involved over 15 000 pediatric participants. A total of more than 20 persistent symptoms and clinical features were reported among children and adolescents. 16.2% (95% confidence interval 8.5% to 28.6%) of the pediatric participants experienced 1 or more persistent symptom(s) at least 3 months post COVID-19. Female gender might be associated with developing certain long COVID symptoms.

LIMITATIONS: Included studies presented with great heterogeneity because of significant variations in the definition of "long COVID," follow up duration, and method. There could be nonresponse and other potential bias.

CONCLUSIONS: Persistent clinical features beyond 3 months among children and adolescents with proven COVID-19 are common and the symptom spectrum is wide. High-quality, prospective studies with proper controls are necessary in the future.}, } @article {pmid37475709, year = {2024}, author = {Kerzhner, O and Berla, E and Har-Even, M and Ratmansky, M and Goor-Aryeh, I}, title = {Consistency of inconsistency in long-COVID-19 pain symptoms persistency: A systematic review and meta-analysis.}, journal = {Pain practice : the official journal of World Institute of Pain}, volume = {24}, number = {1}, pages = {120-159}, doi = {10.1111/papr.13277}, pmid = {37475709}, issn = {1533-2500}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Pain/epidemiology ; Chronic Disease ; }, abstract = {INTRODUCTION: Individuals recovering from acute COVID-19 episodes may continue to suffer from various ongoing symptoms, collectively referred to as Long-COVID. Long-term pain symptoms are amongst the most common and clinically significant symptoms to be reported for this post-COVID-19 syndrome.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the proportions of persisting pain symptoms experienced by individuals past the acute phase of COVID-19 and to identify their associated functional consequences and inflammatory correlates.

METHODS: Two online databases were systematically searched from their inception until 31 March 2022. We searched primary research articles in English, which evaluated individuals after laboratory-confirmed COVID-19 acute phase resolution and specifically reported on pain symptoms and their inflammatory and/or functional outcomes.

RESULTS: Of the 611 identified articles, 26 were included, used for data extraction, and assessed for their methodological quality and risk of bias by two independent reviewers. Pain symptoms were grouped under one of six major pain domains, serving as our primary co-outcomes. Proportional meta-analyses of pooled logit-transformed values of single proportions were performed using the random-effects-restricted maximum-likelihood model. An estimated 8%, 6%, 18%, 18%, 17%, and 12% of individuals continued to report the persistence of chest, gastrointestinal, musculoskeletal joint, musculoskeletal muscle, general body, and nervous system-related pain symptoms, respectively, for up to one year after acute phase resolution of COVID-19. Considerable levels of heterogeneity were demonstrated across all results. Functional and quality-of-life impairments and some inflammatory biomarker elevations were associated with the persistence of long-COVID pain symptoms.

CONCLUSION: This study's findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.}, } @article {pmid37475126, year = {2023}, author = {Hodgson, CL and Broadley, T}, title = {Long COVID-unravelling a complex condition.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {667-668}, doi = {10.1016/S2213-2600(23)00232-1}, pmid = {37475126}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37475125, year = {2023}, author = {Parotto, M and Gyöngyösi, M and Howe, K and Myatra, SN and Ranzani, O and Shankar-Hari, M and Herridge, MS}, title = {Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {739-754}, doi = {10.1016/S2213-2600(23)00239-4}, pmid = {37475125}, issn = {2213-2619}, mesh = {Adult ; Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Critical Illness ; Disease Progression ; }, abstract = {Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after the acute phase, lasting for weeks or months after the initial acute illness. The post-acute sequelae of COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID or post-COVID-19 condition. The substantial burden of this multisystem condition is felt at individual, health-care system, and socioeconomic levels, on an unprecedented scale. Survivors of COVID-19-related critical illness are at risk of the well known sequelae of acute respiratory distress syndrome, sepsis, and chronic critical illness, and these multidimensional morbidities might be difficult to differentiate from the specific effects of SARS-CoV-2 and COVID-19. We provide an overview of the manifestations of post-COVID-19 condition after critical illness in adults. We explore the effects on various organ systems, describe potential pathophysiological mechanisms, and consider the challenges of providing clinical care and support for survivors of critical illness with multisystem manifestations. Research is needed to reduce the incidence of post-acute sequelae of COVID-19-related critical illness and to optimise therapeutic and rehabilitative care and support for patients.}, } @article {pmid37475124, year = {2023}, author = {Pandharipande, P and Williams Roberson, S and Harrison, FE and Wilson, JE and Bastarache, JA and Ely, EW}, title = {Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {726-738}, pmid = {37475124}, issn = {2213-2619}, support = {K23 AG072030/AG/NIA NIH HHS/United States ; R01 GM120484/GM/NIGMS NIH HHS/United States ; RF1 AG075341/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Critical Illness/therapy/psychology ; Cognition ; }, abstract = {Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity. In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19. We review current knowledge of the epidemiology and pathophysiology of persistent neuropsychological impairments, and outline potential preventive strategies based on safe, evidence-based approaches to the management of pain, agitation, delirium, anticoagulation, and ventilator weaning during critical illness. We highlight priorities for current and future research, including possible therapeutic approaches, and offer considerations for health services to address the escalating health burden of long COVID.}, } @article {pmid37474660, year = {2023}, author = {Aiyegbusi, OL and McMullan, C and Hughes, SE and Turner, GM and Subramanian, A and Hotham, R and Davies, EH and Frost, C and Alder, Y and Agyen, L and Buckland, L and Camaradou, J and Chong, A and Jeyes, F and Kumar, S and Matthews, KL and Moore, P and Ormerod, J and Price, G and Saint-Cricq, M and Stanton, D and Walker, A and Haroon, S and Denniston, AK and Calvert, MJ and , }, title = {Considerations for patient and public involvement and engagement in health research.}, journal = {Nature medicine}, volume = {29}, number = {8}, pages = {1922-1929}, pmid = {37474660}, issn = {1546-170X}, support = {MC_PC_21028/MRC_/Medical Research Council/United Kingdom ; MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_21055/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Checklist ; Patient Participation ; Patients ; }, abstract = {Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.}, } @article {pmid37471432, year = {2023}, author = {Alwan, NA and Clutterbuck, D and Pantelic, M and Hayer, J and Fisher, L and Hishmeh, L and Heightman, M and Allsopp, G and Wootton, D and Khan, A and Hastie, C and Jackson, M and Rayner, C and Brown, D and Parrett, E and Jones, G and Smith, K and Clarke, R and Mcfarland, S and Gabbay, M and Banerjee, A and , }, title = {Long Covid active case finding study protocol: A co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways).}, journal = {PloS one}, volume = {18}, number = {7}, pages = {e0284297}, pmid = {37471432}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pilot Projects ; *Delivery of Health Care, Integrated ; United Kingdom ; }, abstract = {BACKGROUND AND AIM: Long Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups' experiences of Long Covid, and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area in London, United Kingdom to test the feasibility of a community-based approach of identifying Long Covid cases that have not been clinically diagnosed and have not been referred to Long Covid specialist services. We will explore the barriers to accessing recognition, care, and support, as well as experiences of stigma and perceived discrimination.

METHODS: This protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, a study leaflet will be distributed in the local community to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed. Potential participants will be assessed according to the study's inclusion criteria and offered the opportunity to participate if they fit them. Awareness of Long Covid and associated symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered a referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic.}, } @article {pmid37470218, year = {2024}, author = {Gallorini, M and Carradori, S and Panieri, E and Sova, M and Saso, L}, title = {Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications.}, journal = {Antioxidants & redox signaling}, volume = {40}, number = {10-12}, pages = {636-662}, doi = {10.1089/ars.2022.0213}, pmid = {37470218}, issn = {1557-7716}, mesh = {Humans ; Kelch-Like ECH-Associated Protein 1/metabolism ; *Neoplasms/drug therapy ; *NF-E2-Related Factor 2/metabolism ; Oxidative Stress/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Recent Advances: Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation. For this reason, there is a growing interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, which requires the accurate knowledge of the cell context and the specific time frame both of NRF2 activation and inhibition. This appears to be an important prerequisite and reflects the extreme complexity of the NRF2 signaling, characterized by an intrinsic dualism that mediates beneficial or detrimental effects even in the same biological process. Critical Issues: Of crucial importance will be to understand whether the NRF2 activity modulation might be exploited to exert beneficial outcomes in patients suffering from pathological conditions, in which the OS and the deregulation of inflammatory processes play a crucial role. Future Directions: In this review, we discuss the dual involvement of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and carcinogenesis and we present an overview of the most recent therapeutic modulators of NRF2, particularly emphasizing on those selected for clinical trials. Antioxid. Redox Signal. 40, 636-662.}, } @article {pmid37469710, year = {2023}, author = {Li, X and Hu, H and Cheng, Y}, title = {Neurological manifestations of long COVID: a single-center one-year experience [Letter].}, journal = {Neuropsychiatric disease and treatment}, volume = {19}, number = {}, pages = {1605-1606}, pmid = {37469710}, issn = {1176-6328}, } @article {pmid37469084, year = {2023}, author = {Rathore, FA and Khalil, MT and Khan, OJ}, title = {Rehabilitation Perspectives in Long COVID-19.}, journal = {JPMA. The Journal of the Pakistan Medical Association}, volume = {73}, number = {7}, pages = {1553-1555}, doi = {10.47391/JPMA.23-54}, pmid = {37469084}, issn = {0030-9982}, mesh = {Humans ; *Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19 ; Exercise Therapy/methods ; }, abstract = {Long COVID is a term used to describe the persistence of symptoms in people who have had COVID-19 for an extended period. It affects multiple systems including neurological (fatigue, brain fog, attention issues, memory issues), neuromuscular (sarcopenia, myositis, arthritis and myopathy), cardiovascular (myopericarditis, right ventricular dysfunction, vasculitis and aortic, arterial and venous thrombosis) and respiratory (pulmonary fibrosis, pleurisy, pulmonary embolism and pneumonitis). This results in functional impairments which adversely affect the quality of life of patients. The rehabilitation of persons who have experienced long COVID-19, also known as "long haulers," is a relatively new field of study. We have described potential rehabilitation interventions to improve functional capacity and quality of life in patients with long COVID. These rehabilitation interventions include but are not limited to, endurance, flexibility and strength training, pulmonary rehabilitation, task specific exercises to improve Activities of Daily Living (ADL), psychological rehabilitation, medical rehabilitation, pain management and management of dysphagia.}, } @article {pmid37468884, year = {2023}, author = {Kennedy, J and Parker, M and Seaborne, M and Mhereeg, M and Walker, A and Walker, V and Denaxas, S and Kennedy, N and Katikireddi, SV and Brophy, S}, title = {Healthcare use attributable to COVID-19: a propensity-matched national electronic health records cohort study of 249,390 people in Wales, UK.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {259}, pmid = {37468884}, issn = {1741-7015}, support = {MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/4/MRC_/Medical Research Council/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; SPHSU17/CSO_/Chief Scientist Office/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; COV-LT-0009/DH_/Department of Health/United Kingdom ; HDR-9006/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/diagnosis/epidemiology/complications ; COVID-19 Testing ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Wales/epidemiology ; Electronic Health Records ; *Virus Diseases ; Delivery of Health Care ; Fatigue ; }, abstract = {BACKGROUND: To determine the extent and nature of changes associated with COVID-19 infection in terms of healthcare utilisation, this study observed healthcare contact 1 to 4 and 5 to 24 weeks following a COVID-19 diagnosis compared to propensity-matched controls.

METHODS: Two hundred forty nine thousand three hundred ninety Welsh individuals with a positive reverse transcription-polymerase chain reaction (RT-PCR) test were identified from data from national PCR test results. After elimination criteria, 98,600 positive individuals were matched to test negative and never tested controls using propensity matching. Cohorts were split on test location. Tests could be taken in either the hospital or community. Controls were those who had tested negative in their respective environments. Survival analysis was utilised for first clinical outcomes which are grouped into primary and secondary. Primary outcomes include post-viral-illness and fatigue as an indication of long-COVID. Secondary outcomes include clinical terminology concepts for embolism, respiratory conditions, mental health conditions, fit notes, or hospital attendance. Increased instantaneous risk for positive individuals was quantified using hazard ratios (HR) from Cox regression, while absolute risk (AR) and relative risk were quantified using life table analysis.

RESULTS: Analysis was conducted using all individuals and stratified by test location. Cases are compared to controls from the same test location. Fatigue (HR: 1.77, 95% CI: 1.34-2.25, p =  < 0.001) and embolism (HR: 1.50, 95% CI: 1.15-1.97, p = 0.003) were more likely to occur in all positive individuals in the first 4 weeks; however, anxiety and depression (HR: 0.83, 95% CI: 0.73-0.95, p = 0.007) were less likely. Positive individuals continued to be more at risk of fatigue (HR: 1.47, 95% CI: 1.24-1.75, p =  < 0.001) and embolism (HR: 1.51, 95% CI: 1.13-2.02, p = 0.005) after 4 weeks. All positive individuals are also at greater risk of post-viral illness (HR: 4.57, 95% CI: 1.77-11.80, p = 0.002). Despite statistical association between testing positive and several conditions, life table analysis shows that only a small minority of the study population were affected.

CONCLUSIONS: Community COVID-19 disease is associated with increased risks of post-viral-illness, fatigue, embolism, and respiratory conditions. Despite elevated risks, the absolute healthcare burden is low. Subsequently, either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare.}, } @article {pmid37468867, year = {2023}, author = {Zhang, D and Weng, S and Xia, C and Ren, Y and Liu, Z and Xu, Y and Yang, X and Wu, R and Peng, L and Sun, L and Zhu, J and Liang, X and Jia, Y and Wang, H and Chen, Q and Liu, D and Chen, Y and Guo, H and Han, X and Jin, Z and Chen, C and Yang, X and Li, Z and Huang, H}, title = {Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {264}, pmid = {37468867}, issn = {1741-7015}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Aftercare ; Quality of Life ; SARS-CoV-2 ; Patient Discharge ; Feces/microbiology ; Bacteria/genetics ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19.

METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics.

RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate.

CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.}, } @article {pmid37468320, year = {2023}, author = {Maurya, DK and Sharma, D}, title = {Culinary spices and herbs in managing early and long-COVID-19 complications: A comprehensive review.}, journal = {Phytotherapy research : PTR}, volume = {37}, number = {11}, pages = {4908-4931}, doi = {10.1002/ptr.7957}, pmid = {37468320}, issn = {1099-1573}, support = {//Department of Atomic Energy, Govt. of India/ ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; Food ; }, abstract = {Human race is preparing for the upsurge and aftermath of COVID-19 pandemic complicated by novel variants, new waves, variable mortality rate, and post-COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non-pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well-known as well as less-known but scientifically testable mechanisms. Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of "food-based" traditional decoction to moderate COVID-19 disease and long-COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID-19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs-based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS-CoV-2 transmission, long-COVID symptoms, and COVID-19 disease progression.}, } @article {pmid37468178, year = {2023}, author = {Iba, T and Levy, JH}, title = {A commentary on "Thromboinflammation in long COVID - the elusive key to post-infection sequelae?".}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {8}, pages = {2061-2063}, doi = {10.1016/j.jtha.2023.05.018}, pmid = {37468178}, issn = {1538-7836}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Thromboinflammation ; Inflammation ; *COVID-19 ; *Thrombosis/etiology ; }, } @article {pmid37466117, year = {2023}, author = {Abrams, RMC and Zhou, L and Shin, SC}, title = {Persistent post-COVID-19 neuromuscular symptoms.}, journal = {Muscle & nerve}, volume = {68}, number = {4}, pages = {350-355}, doi = {10.1002/mus.27940}, pmid = {37466117}, issn = {1097-4598}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Myalgia/etiology ; Paresthesia/etiology ; Quality of Life ; Fatigue/etiology ; *Primary Dysautonomias ; }, abstract = {Neuromuscular symptoms may develop or persist after resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides residual sensorimotor symptoms associated with acute neuromuscular complications of coronavirus disease-2019 (COVID-19), such as Guillain-Barré syndrome, critical illness neuromyopathy, and rhabdomyolysis, patients may report persistent autonomic symptoms, sensory symptoms, and muscle symptoms in the absence of these acute complications, including palpitations, orthostatic dizziness and intolerance, paresthesia, myalgia, and fatigue. These symptoms may be associated with long COVID, also known as post-COVID-19 conditions or postacute sequelae of SARS-CoV-2 infection, which may significantly impact quality of life. Managing these symptoms represents a challenge for health-care providers. Recent advances have identified small-fiber neuropathy as a potential etiology that may underlie autonomic dysfunction and paresthesia in some long COVID patients. The pathogenic mechanisms underlying myalgia and fatigue remain elusive and need to be investigated. Herein we review the current state of knowledge regarding the evaluation and management of patients with persistent post-COVID-19 neuromuscular symptoms.}, } @article {pmid37464515, year = {2023}, author = {Nasir, M and Cook, N and Parras, D and Mukherjee, S and Miller, G and Ferres, JL and Chung-Bridges, K}, title = {Using Data Science and a Health Equity Lens to Identify Long-COVID Sequelae Among Medically Underserved Populations.}, journal = {Journal of health care for the poor and underserved}, volume = {34}, number = {2}, pages = {521-534}, doi = {10.1353/hpu.2023.0047}, pmid = {37464515}, issn = {1548-6869}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Data Science ; Medically Underserved Area ; *Health Equity ; *COVID-19/epidemiology ; Disease Progression ; }, abstract = {Understanding how post-acute COVID-19 syndrome (PACS or long COVID) manifests among underserved populations, who experienced a disproportionate burden of acute COVID-19, can help providers and policymakers better address this ongoing crisis. To identify clinical sequelae of long COVID among underserved populations treated in the primary care safety net, we conducted a causal impact analysis with electronic health records (EHR) to compare symptoms among community health center patients who tested positive (n=4,091) and negative (n=7,118) for acute COVID-19. We found 18 sequelae with statistical significance and causal dependence among patients who had a visit after 60 days or more following acute COVID-19. These sequelae encompass most organ systems and include breathing abnormalities, malaise and fatigue, and headache. This study adds to current knowledge about how long COVID manifests in a large, underserved population.}, } @article {pmid37463787, year = {2023}, author = {Wolff Sagy, Y and Feldhamer, I and Brammli-Greenberg, S and Lavie, G}, title = {Estimating the economic burden of long-Covid: the additive cost of healthcare utilisation among COVID-19 recoverees in Israel.}, journal = {BMJ global health}, volume = {8}, number = {7}, pages = {}, pmid = {37463787}, issn = {2059-7908}, mesh = {Humans ; Aged ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Cohort Studies ; *Post-Acute COVID-19 Syndrome ; Israel/epidemiology ; Financial Stress ; *COVID-19 ; SARS-CoV-2 ; Delivery of Health Care ; Health Care Costs ; Patient Acceptance of Health Care ; }, abstract = {INTRODUCTION: Postacute sequelae resulting from SARS-CoV-2 infections (LONG-COVID) have been reported. The resulting added economic burden from the perspective of healthcare organisations is not clear. Therefore, this study aims to evaluate the additive healthcare costs among COVID-19 recoverees, in a large community-dwelling general population, as incurred by an insurer-provider organisation over time.

METHODS: In this historical cohort study, cost data from Clalit Health Services (CHS) were analysed. The primary endpoint was the direct cost incurred by CHS per month per person. Costs were measured for COVID-19 recoverees and matched controls, from January 2019 to January 2022. Difference in differences (DiDs) were calculated as the difference in mean monthly costs in cases and controls in the post-COVID-19 individual period, deducing their cost difference in a prepandemic 12 months baseline period.

RESULTS: Among N=642 868 community-dwelling COVID-19 recoverees, 268 948 (40.8%) were 0-19 years old and 63 051 (9.6%) were 60 years or older. A total of 16 017 (2.5%) of recoverees had been hospitalised during the acute phase of the COVID-19 disease. Costs in cases and controls converged after 16 months from recovery. The mean monthly cost incurred by CHS per COVID-19 recoverees over up to 15 months (mean: 8.25) of post-COVID-19 follow-up was higher by 8.2% (US$8.2) compared with matched controls. The excess cost attributable to post-COVID-19 effects (DID) was 7.6% of the cost in controls (US$7.7 per patient per month). Both net and relative DIDs were substantially higher in patients who required hospitalisation during the acute phase of COVID-19 and in older adults. Excess in hospitalisations, primary care physicians and medical specialists' visits-related costs were observed.

CONCLUSIONS: Long-term effects of SARS-CoV-2 infections translate into excess healthcare costs, months after recovery, hence requiring adjustments of funds allocation. These excess costs gradually diminish after recoveree, returning to baseline differences 16 months after recoveree.}, } @article {pmid37462272, year = {2023}, author = {Smith, TC}, title = {Long COVID: Alice Evans, Brucellosis, and Reflections on Infectious Causes of Chronic Disease.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {12}, pages = {1644-1647}, doi = {10.1093/cid/ciad427}, pmid = {37462272}, issn = {1537-6591}, mesh = {Humans ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Brucellosis/complications/diagnosis/epidemiology ; Chronic Disease ; }, abstract = {Despite more than a century of research on the link between infection and chronic diseases, we again find ourselves flummoxed by a new pathogen that causes long-term impairment. Patients have reported being ignored or minimized, resources are lacking for diagnosis and treatment, and frustrated individuals are turning outside of the scientific profession for answers. The experience mirrors that of American Society for Microbiology past president Alice C. Evans. Accidentally infected with Brucella melitensis during her laboratory research, Evans was chronically ill for more than 20 years, during which time friends, colleagues, and physicians cast doubt on her illness. As a result, she argued passionately for improved diagnostics and for those who reported chronic infection to be taken seriously rather than presumed to be "malingering" or using their illness for financial benefit. Lessons from Evans' experience are useful as we work toward understanding long COVID and patients suffering from the condition.}, } @article {pmid37461683, year = {2023}, author = {Souquette, A and Crawford, JC and Wolf, J and Blair, A and Agrawal, M and Boywid, L and McNair, K and Hysmith, ND and Hundman, C and Bahadoran, A and Arnold, SR and , and Smallwood, HS and Green, A and Thomas, PG}, title = {Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.07.06.548022}, pmid = {37461683}, issn = {2692-8205}, support = {R01 AI128756/AI/NIAID NIH HHS/United States ; }, abstract = {Previous studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.}, } @article {pmid37461092, year = {2023}, author = {Kabir, MF and Yin, KN and Jeffree, MS and Ahmedy, FB and Jahan, S and Islam, MW and Jahid, IK and Sivan, M and Chakrovorty, SK and Hossain, KMA}, title = {Profile of long COVID symptoms needing rehabilitation: a cross-sectional household survey of 12,925 SARS-CoV-2 cases between July and December 2021 in Bangladesh.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {81}, number = {1}, pages = {132}, pmid = {37461092}, issn = {0778-7367}, abstract = {BACKGROUND AND AIMS: It is important to determine the profile of long COVID (LC) symptoms within the scope of rehabilitation in Bangladesh. This study's objective was to estimate the newly experienced long COVID symptoms needing rehabilitation by determining the prevalence and spectrum of impairments due to LC in Bangladesh.

METHODS: A Cross-sectional household survey of 12,925 COVID-19 patients confirmed by RT-PCR from 24 testing facilities in Bangladesh. LC was diagnosed according to WHO working group definition. COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) was used to determine the symptom responses, symptom severity, new long COVID symptoms, and scope of rehabilitation.

RESULTS: The population proportion of LC symptoms requiring rehabilitation interventions are 0.22 [95% CI, 0.20-0.24] in Bangladeshi people diagnosed with SARS-CoV-2. Among them, 0.08 [95% CI, 0.07-0.09] had mild, 0.07 [95% CI, 0.06-0.09] had moderate, and 0.05 [95% CI, 0.04-0.06] had severe long COVID symptoms (LCS). There was a significant positive correlation between LCS and functional disabilities (r = 0.889, p < 0.001), while a negative correlation was observed between the severity of symptoms and overall health (r=-0.658, p < 0.001). In comparison to the pre-COVID status, 17 new LCS were observed and the increase in the scope of rehabilitation intervention among LCS ranged between 0.01 [95% CI, 0.001-0.01] and 0.21 [95% CI, 0.19-0.22]. In Bangladesh, 59% (n = 334) of the LC cases are out of reach for any rehabilitation interventions.

CONCLUSION: Nearly one-fourth of Bangladeshi Post-COVID-19 have long COVID (LC). Seventeen symptoms (LCS) were observed and more than half of the populations having long COVID are out of reach of any rehabilitation facilities.}, } @article {pmid37460909, year = {2023}, author = {Constantin, T and Pék, T and Horváth, Z and Garan, D and Szabó, AJ}, title = {Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID.}, journal = {Inflammopharmacology}, volume = {31}, number = {5}, pages = {2221-2236}, pmid = {37460909}, issn = {1568-5608}, mesh = {Adult ; SARS-CoV-2 ; Pandemics ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; }, abstract = {The COVID-19 pandemic caused by the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) has significantly affected people around the world, leading to substantial morbidity and mortality. Although the pandemic has affected people of all ages, there is increasing evidence that children are less susceptible to SARS-CoV-2 infection and are more likely to experience milder symptoms than adults. However, children with COVID-19 can still develop serious complications, such as multisystem inflammatory syndrome in children (MIS-C). This narrative review of the literature provides an overview of the epidemiology and immune pathology of SARS-CoV-2 infection and MIS-C in children. The review also examines the genetics of COVID-19 and MIS-C in children, including the genetic factors that can influence the susceptibility and severity of the diseases and their implications for personalized medicine and vaccination strategies. By examining current evidence and insights from the literature, this review aims to contribute to the development of effective prevention and treatment strategies for COVID-19, MIS-C, and long COVID syndromes in children.}, } @article {pmid37459027, year = {2023}, author = {Sreelakshmi, PR and Tandale, BV and Jadhav, AV and Vaidya, RR and Walimbhe, AM and Jadhav, S}, title = {A scoping review of persistent symptoms after COVID infection at different follow-up periods.}, journal = {Indian journal of public health}, volume = {67}, number = {2}, pages = {292-300}, doi = {10.4103/ijph.ijph_1178_22}, pmid = {37459027}, issn = {0019-557X}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; India/epidemiology ; }, abstract = {The clinical entity termed as long COVID has gained importance in the recent past. As this phenomenon is still evolving, it is important to document the magnitude of the syndrome during different time periods. This scoping review attempts to synthesize evidence generated from longitudinal studies which have follow-up periods beyond 3 months, up to 12 months. The review also documents the reported prevalence of long COVID for the different regions of the World Health Organization. Longitudinal studies published till March 2022 were systematically searched on PubMed, Google Scholar, and medRxiv. Among the identified 594 studies, 48 were included in this review. Data from selected studies were synthesized. The overall pooled prevalence of long COVID was 49% (40%-58%). The pooled estimates after 3 months, 4-6 months, 7-9 months, and 10-12 months were 44% (32%-57%), 50% (43%-57%), 49% (37%-62%), and 54% (46%-62%), respectively. Eastern Mediterranean Region (EMR) had the highest pooled prevalence of 63% (34%-92%] and the South East Asian Region (SEAR) had the least pooled estimate of 15% (10%-21%). The study brings out the high prevalence of long COVID even after 12 months of follow-up. It also shows the regional differences in the reported prevalence of the syndrome. This review highlights the need for well-planned follow-up studies, especially in developing nations to understand the magnitude and the pattern of long COVID-related symptoms as they emerge.}, } @article {pmid37458668, year = {2023}, author = {Glinianowicz, M and Ciura, D and Burnatowska, E and Olszanecka-Glinianowicz, M}, title = {Psychological effects of the COVID-19 pandemic - what do we know about them?.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {13}, pages = {6445-6458}, doi = {10.26355/eurrev_202307_33006}, pmid = {37458668}, issn = {2284-0729}, mesh = {Child ; Humans ; Adolescent ; *COVID-19/epidemiology ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Anxiety/epidemiology/psychology ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic was a shock to the whole world. This pandemic caused not only many deaths of people of all ages and health effects that are still difficult to assess, but also economic, and psychological ones. Numerous studies have shown that chronic stress related to social isolation and fear of contagion increased the rates of development of anxiety, depression syndrome, emotional eating, and posttraumatic stress disorder (PTSD). The increased rate of substance use and antidepressant drugs has also been observed. Depression is included in the symptoms of long-COVID syndrome. The data on the deterioration of mental states of children and adolescents during the COVID-19 pandemic are particularly worrying. Some studies have shown increased suicide rates during and after the COVID-19 pandemic. The deterioration of mental health can also have long-term consequences in terms of physical health, for example, emotional eating (EE) associated with depressed mood and anxiety may increase the incidence of binge eating disorder (BED) and addictive eating. Consequently, the number of patients with overweight and obesity and its complications will increase. Problems related to the deterioration of the mental and physical health of the population will increase the burden on the healthcare system. Another important problem is psychological disturbances related to the COVID-19 pandemic developed in healthcare workers. It is necessary to take systemic actions aimed at improving mental health, although it will not be easy in the era of the general global economic crisis, which may deepen the psychological problems from the time of the pandemic. Therefore, the aim of our manuscript is to analyze the available data on the psychological effects of the COVID-19 pandemic on the general population and healthcare workers.}, } @article {pmid37458167, year = {2023}, author = {García-González, L and Martí-Sarrias, A and Puertas, MC and Bayón-Gil, Á and Resa-Infante, P and Martinez-Picado, J and Navarro, A and Acosta, S}, title = {Understanding the neurological implications of acute and long COVID using brain organoids.}, journal = {Disease models & mechanisms}, volume = {16}, number = {7}, pages = {}, pmid = {37458167}, issn = {1754-8411}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brain ; Organoids ; }, abstract = {As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal. In vitro and in vivo modeling suggest that SARS-CoV-2 infection drives changes within neurons, glia and the brain vasculature. In this Review, we summarize the current understanding of the neuropathology of acute and long COVID, with particular emphasis on the knowledge derived from brain organoid models. We highlight the advantages and main limitations of brain organoids, leveraging their human-derived origin, their similarity in cellular and tissue architecture to human tissues, and their potential to decipher the pathophysiology of long COVID.}, } @article {pmid37457901, year = {2023}, author = {Quan, M and Wang, X and Gong, M and Wang, Q and Li, Y and Jia, J}, title = {Post-COVID cognitive dysfunction: current status and research recommendations for high risk population.}, journal = {The Lancet regional health. Western Pacific}, volume = {38}, number = {}, pages = {100836}, pmid = {37457901}, issn = {2666-6065}, abstract = {Post-COVID cognitive dysfunction (PCCD) is a condition in which patients with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, usually three months from the onset, exhibit subsequent cognitive impairment in various cognitive domains, and cannot be explained by an alternative diagnosis. While our knowledge of the risk factors and management strategy of PCCD is still incomplete, it is necessary to integrate current epidemiology, diagnosis and treatment evidence, and form consensus criteria to better understand this disease to improve disease management. Identifying the risk factors and vulnerable population of PCCD and providing reliable strategies for effective prevention and management is urgently needed. In this paper, we reviewed epidemiology, diagnostic markers, risk factors and available treatments on the disease, formed research recommendation framework for vulnerable population, under the background of post-COVID period.}, } @article {pmid37457578, year = {2023}, author = {Magel, T and Meagher, E and Boulter, T and Albert, A and Tsai, M and Muñoz, C and Carlsten, C and Johnston, J and Wong, AW and Shah, A and Ryerson, C and Mckay, RJ and Nacul, L}, title = {Fatigue presentation, severity, and related outcomes in a prospective cohort following post-COVID-19 hospitalization in British Columbia, Canada.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1179783}, pmid = {37457578}, issn = {2296-858X}, abstract = {INTRODUCTION: Increasing evidence on long-term health outcomes following SARS CoV-2 infection shows post-viral symptoms can persist for months. These symptoms are often consistent with those of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS). The aim of the present study was to examine the prevalence and outcome predictors of post-viral fatigue and related symptoms 3- and 6-months following symptom onset.

METHODS: A prospective cohort of patients hospitalized with Coronavirus disease (COVID-19) (n = 88) were recruited from a Post-COVID-19 Respiratory Clinic (PCRC) in Vancouver, Canada to examine predictors of long-term fatigue and substantial fatigue. Multivariable mixed effects analyses examined the relationship between patient predictors, including pre-existing comorbidities, patient reported outcome measures, and fatigue and substantial fatigue at follow-up.

RESULTS: The number of patients experiencing fatigue or substantial fatigue at 3 months post-infection were 58 (67%) and 14 (16%) respectively. At 6 months these numbers declined to 47 (60%) patients experiencing fatigue and 6 (6%) experiencing substantial fatigue. Adjusted analysis, for sex, age, and time, revealed the number of pre-existing comorbidities to be associated with fatigue (OR 2.21; 95% CI 1.09-4.49; 0.028) and substantial fatigue (OR 1.73; 95% CI 1.06-2.95; 0.033) at 3 months follow-up. Except for shortness of breath, self-care, and follow-up time, all follow-up variables were found to be associated with fatigue and substantial fatigue at 3 months.

CONCLUSION: Fatigue and substantial fatigue are common after COVID-19 infection but often diminish over time. A significant number of patients continue to exhibit long-term fatigue at 6 months follow-up. Further research is needed to clarify the causality of viral infections in the development and severity of fatigue as a symptom and in meeting post-viral fatigue syndrome or ME/CFS diagnostic criteria.}, } @article {pmid37457560, year = {2023}, author = {Qi, P and Huang, M and Zhu, H}, title = {Exploring potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1191354}, pmid = {37457560}, issn = {2296-858X}, abstract = {BACKGROUND: The negative impact of long COVID on social life and human health is increasingly prominent, and the elevated risk of cardiovascular disease in patients recovering from COVID-19 has also been fully confirmed. However, the pathogenesis of long COVID-related inflammatory cardiomyopathy is still unclear. Here, we explore potential biomarkers and therapeutic targets of long COVID-associated inflammatory cardiomyopathy.

METHODS: Datasets that met the study requirements were identified in Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were obtained by the algorithm. Then, functional enrichment analysis was performed to explore the basic molecular mechanisms and biological processes associated with DEGs. A protein-protein interaction (PPI) network was constructed and analyzed to identify hub genes among the common DEGs. Finally, a third dataset was introduced for validation.

RESULTS: Ultimately, 3,098 upregulated DEGs and 1965 downregulated DEGs were extracted from the inflammatory cardiomyopathy dataset. A total of 89 upregulated DEGs and 217 downregulated DEGs were extracted from the dataset of convalescent COVID patients. Enrichment analysis and construction of the PPI network confirmed VEGFA, FOXO1, CXCR4, and SMAD4 as upregulated hub genes and KRAS and TXN as downregulated hub genes. The separate dataset of patients with COVID-19 infection used for verification led to speculation that long COVID-associated inflammatory cardiomyopathy is mainly attributable to the immune-mediated response and inflammation rather than to direct infection of cells by the virus.

CONCLUSION: Screening of potential biomarkers and therapeutic targets sheds new light on the pathogenesis of long COVID-associated inflammatory cardiomyopathy as well as potential therapeutic approaches. Further clinical studies are needed to explore these possibilities in light of the increasingly severe negative impacts of long COVID.}, } @article {pmid37457558, year = {2023}, author = {Hannestad, U and Apostolou, E and Sjögren, P and Bragée, B and Polo, O and Bertilson, BC and Rosén, A}, title = {Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1208181}, pmid = {37457558}, issn = {2296-858X}, abstract = {The post-viral fatigue syndromes long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have multiple, potentially overlapping, pathological processes. These include persisting reservoirs of virus, e.g., SARS-CoV-2 in long COVID patient's tissues, immune dysregulation with or without reactivation of underlying pathogens, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV6), as we recently described in ME/CFS, and possibly yet unidentified viruses. In the present study we tested saliva samples from two cohorts for IgG against human adenovirus (HAdV): patients with ME/CFS (n = 84) and healthy controls (n = 94), with either mild/asymptomatic SARS-CoV-2 infection or no infection. A significantly elevated anti-HAdV IgG response after SARS-CoV-2 infection was detected exclusively in the patient cohort. Longitudinal/time analysis, before and after COVID-19, in the very same individuals confirmed HAdV IgG elevation after. In plasma there was no HAdV IgG elevation. We conclude that COVID-19 triggered reactivation of dormant HAdV in the oral mucosa of chronic fatigue patients indicating an exhausted dysfunctional antiviral immune response in ME/CFS, allowing reactivation of adenovirus upon stress encounter such as COVID-19. These novel findings should be considered in clinical practice for identification of patients that may benefit from therapy that targets HAdV as well.}, } @article {pmid37457286, year = {2023}, author = {Umakanthan, S and Monice, M and Mehboob, S and Jones, CL and Lawrence, S}, title = {Post-acute (long) COVID-19 quality of life: validation of the German version of (PAC19QoL) instrument.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1163360}, pmid = {37457286}, issn = {2296-2565}, mesh = {Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Reproducibility of Results ; Language ; }, abstract = {PURPOSE: The aim of our study was to validate a German translation of the post-acute (long) COVID-19 quality of life (PAC-19QoL) instrument among German patients with long COVID-19 syndrome.

PATIENTS AND METHODS: The PAC-19QoL instrument was translated into the German language and administrated to patients with long COVID-19 syndrome. Cronbach's alpha coefficient was used to analyze the internal consistency of the instrument. Construction validity was evaluated by using Pearson's correlation coefficient and Spearman's rank correlation. Scores of patients and controls were compared using the Mann-Whitney U-test.

RESULTS: A total of 45 asymptomatic and 41 symptomatic participants were included. In total, 41 patients with long COVID-19 syndrome completed the PAC-19QoL and EQ-5D-5L questionnaires. PAC-19QoL domain scores were significantly different between symptomatic and asymptomatic participants. All items achieved a Cronbach's alpha >0.7. There was a significant correlation between all domains on the test (p < 0.001), with the highest correlation between total (r = 0.994) and domain 1 (r = 0.991). Spearman's rank correlation analysis confirmed that the instrument items correlated with the objective PAC-19QoL examination findings.

CONCLUSION: The German version of the instrument is valid and reliable and can be a suitable tool for research and daily clinical practice among patients with long COVID-19 syndrome.}, } @article {pmid37452829, year = {2023}, author = {Woo, MS and Shafiq, M and Fitzek, A and Dottermusch, M and Altmeppen, H and Mohammadi, B and Mayer, C and Bal, LC and Raich, L and Matschke, J and Krasemann, S and Pfefferle, S and Brehm, TT and Lütgehetmann, M and Schädler, J and Addo, MM and Schulze Zur Wiesch, J and Ondruschka, B and Friese, MA and Glatzel, M}, title = {Vagus nerve inflammation contributes to dysautonomia in COVID-19.}, journal = {Acta neuropathologica}, volume = {146}, number = {3}, pages = {387-394}, pmid = {37452829}, issn = {1432-0533}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Endothelial Cells ; Inflammation ; *Primary Dysautonomias/etiology ; Vagus Nerve ; }, abstract = {Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.}, } @article {pmid37452676, year = {2023}, author = {Dickey, T and Junqueira, H}, title = {COVID-19 scent dog research highlights and synthesis during the pandemic of December 2019-April 2023.}, journal = {Journal of osteopathic medicine}, volume = {123}, number = {11}, pages = {509-521}, pmid = {37452676}, issn = {2702-3648}, mesh = {Dogs ; Humans ; Animals ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Pandemics/prevention & control ; COVID-19 Testing ; Odorants ; Post-Acute COVID-19 Syndrome ; }, abstract = {CONTEXT: This review was undertaken to provide information concerning the advancement of research in the area of COVID-19 screening and testing during the worldwide pandemic from December 2019 through April 2023. In this review, we have examined the safety, effectiveness, and practicality of utilizing trained scent dogs in clinical and public situations for COVID-19 screening. Specifically, results of 29 trained scent dog screening peer-reviewed studies were compared with results of real-time reverse-transcription polymerase chain reaction (RT-PCR) and rapid antigen (RAG) COVID-19 testing methods.

OBJECTIVES: The review aims to systematically evaluate the strengths and weaknesses of utilizing trained scent dogs in COVID-19 screening.

METHODS: At the time of submission of our earlier review paper in August 2021, we found only four peer-reviewed COVID-19 scent dog papers: three clinical research studies and one preprint perspective paper. In March and April 2023, the first author conducted new literature searches of the MEDLINE/PubMed, Google Scholar, and Cochrane Library websites. Again, the keyword phrases utilized for the searches included "COVID detection dogs," "COVID scent dogs," and "COVID sniffer dogs." The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Checklist was followed to ensure that our review adhered to evidence-based guidelines for reporting. Utilizing the results of the reviewed papers, we compiled statistics to intercompare and summarize basic information concerning the scent dogs and their training, the populations of the study participants, the types of sampling methods, the comparative tests utilized, and the effectiveness of the scent dog screening.

RESULTS: A total of 8,043 references were identified through our literature search. After removal of duplicates, there were 7,843 references that were screened. Of these, 100 were considered for full-text eligibility, 43 were included for qualitative synthesis, and 29 were utilized for quantitative analysis. The most relevant peer-reviewed COVID-19 scent dog references were identified and categorized. Utilizing all of the scent dog results provided for this review, we found that 92.3 % of the studies reached sensitivities exceeding 80 and 32.0 % of the studies exceeding specificities of 97 %. However, 84.0 % of the studies reported specificities above 90 %. Highlights demonstrating the effectiveness of the scent dogs include: (1) samples of breath, saliva, trachea-bronchial secretions and urine as well as face masks and articles of clothing can be utilized; (2) trained COVID-19 scent dogs can detect presymptomatic and asymptomatic patients; (3) scent dogs can detect new SARS-CoV-2 variants and Long COVID-19; and (4) scent dogs can differentiate SARS-CoV-2 infections from infections with other novel respiratory viruses.

CONCLUSIONS: The effectiveness of the trained scent dog method is comparable to or in some cases superior to the real-time RT-PCR test and the RAG test. Trained scent dogs can be effectively utilized to provide quick (seconds to minutes), nonintrusive, and accurate results in public settings and thus reduce the spread of the COVID-19 virus or other viruses. Finally, scent dog research as described in this paper can serve to increase the medical community's and public's knowledge and acceptance of medical scent dogs as major contributors to global efforts to fight diseases.}, } @article {pmid37452024, year = {2023}, author = {Woodruff, MC and Bonham, KS and Anam, FA and Walker, TA and Faliti, CE and Ishii, Y and Kaminski, CY and Ruunstrom, MC and Cooper, KR and Truong, AD and Dixit, AN and Han, JE and Ramonell, RP and Haddad, NS and Rudolph, ME and Yalavarthi, S and Betin, V and Natoli, T and Navaz, S and Jenks, SA and Zuo, Y and Knight, JS and Khosroshahi, A and Lee, FE and Sanz, I}, title = {Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {4201}, pmid = {37452024}, issn = {2041-1723}, support = {T32 HL116271/HL/NHLBI NIH HHS/United States ; P01 AI125180/AI/NIAID NIH HHS/United States ; K08 AR080205/AR/NIAMS NIH HHS/United States ; U54 CA260563/CA/NCI NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; U19 AI110483/AI/NIAID NIH HHS/United States ; U01 AI141993/AI/NIAID NIH HHS/United States ; R37 AI049660/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Neutrophils ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Inflammation ; Antiviral Agents ; Disease Progression ; }, abstract = {While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.}, } @article {pmid37451202, year = {2023}, author = {Daniel, CL and Fillingim, S and James, J and Bassler, J and Lee, A}, title = {Long COVID prevalence and associated characteristics among a South Alabama population.}, journal = {Public health}, volume = {221}, number = {}, pages = {135-141}, doi = {10.1016/j.puhe.2023.06.008}, pmid = {37451202}, issn = {1476-5616}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Male ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Alabama/epidemiology ; COVID-19 Testing ; Longitudinal Studies ; Prevalence ; Quality of Life ; }, abstract = {OBJECTIVES: Long COVID can significantly impact a patient's quality of life. Defined as persistence or emergence of symptoms 4+ weeks after initial COVID-19 diagnosis, long COVID can result in functional impairments, pulmonary issues, and neuropsychiatric conditions, among others. This study aims to identify long COVID risk factors and prevalence in a south Alabama (US) patient population.

STUDY DESIGN: This was a longitudinal cohort study.

METHODS: Postdiagnosis standardized phone interviews (baseline, 6 months, and 12 months) from April 2020 to July 2021 with patients testing positive through a large healthcare system. Interviews gathered data on sociodemographics, comorbidities, acute illness, and long COVID. Relationships between 1+ ongoing symptoms and variables of interest were assessed using a generalized estimating equation to conduct multivariate analysis.

RESULTS: Of the 516 participants, most were female (65%) and African American (57%, n = 293), with a median (interquartile range) age of 41.1 (25.3-54.6) years. Retention was 70% (n = 359) at 6 months and 58% (n = 301) at 12 months. Participants reporting 1+ persistent symptoms were 20% and 17% at 6 and 12 months, respectively. Illness severity (P < 0.0001) and COVID-related emergency room visit with hospital admission at the time of diagnosis (P = 0.0018) were significantly associated with increased long COVID risk.

CONCLUSIONS: This study found substantial rates of long COVID within our population, with stable rates at 6 and 12 months, indicating illness persistence. Our findings support growing concern for long COVID as a persistent issue within the medical community, with potential to impact patient health for years. Larger, more uniform studies are required to further characterize disease risk factors and clinical course to inform the disease management.}, } @article {pmid37449405, year = {2023}, author = {Sonnweber, T and Birgit, S and Weiss, G and Löffler-Ragg, J}, title = {Pulmonary recovery after COVID-19 - a review.}, journal = {Expert review of respiratory medicine}, volume = {17}, number = {6}, pages = {447-457}, doi = {10.1080/17476348.2023.2210837}, pmid = {37449405}, issn = {1747-6356}, mesh = {Adult ; Humans ; *COVID-19/pathology ; SARS-CoV-2 ; Lung/diagnostic imaging/pathology ; }, abstract = {INTRODUCTION: COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). As the respiratory tract is the primary site of infection and host-mediated inflammatory responses, pathologies and dysfunction of the respiratory system characterize the severe disease and are typically associated with the need for oxygen supply or even ventilator support. In survivors of severe COVID-19, computed tomography follow-up frequently reveals structural lung abnormalities, and one-third of individuals who were hospitalized during acute COVID-19 demonstrate persisting lung abnormalities for at least 12 months after disease onset.

AREAS COVERED: This review summarizes current evidence on pulmonary recovery after COVID-19, focusing on adult patients who suffered from COVID-19 pneumonia.

EXPERT OPINION: Severe COVID-19 is associated with a high frequency of persisting lung abnormalities at follow-up. The long-term consequences of these findings remain elusive and urge further evaluation to identify individuals at risk for COVID-19 long-term consequences.}, } @article {pmid37448914, year = {2023}, author = {Rao, CM and Mohapatra, AK and Patnaik, AK and Panda, PS and Behera, PR}, title = {An in-depth appraisal of clinico-biochemical and radiological findings of COVID-19 patients during the COVID-19 pandemic in a dedicated COVID Care Hospital in Eastern India and its outcome in relation to the COVAXIN vaccination status: A 2-year study.}, journal = {Journal of family medicine and primary care}, volume = {12}, number = {5}, pages = {971-978}, pmid = {37448914}, issn = {2249-4863}, abstract = {INTRODUCTION: COVID-19 pandemic hit Odisha province from April 2020 to December 2020, then from April 2021 to August 2021 and from February 2022 to April 2022 as the first, second, and third waves, respectively, with the most severe form witnessed during the second wave. Kalinga Institute of Medical Sciences hospital in Odisha was declared a Dedicated COVID Hospital (DCH) during those three waves and witnessed 9485 cases of admissions among which there were 1214 deaths. COVAXIN vaccination of the vulnerable population was launched in February 2021 onwards. This study has been done to know the clinic-biochemical profiles, radiologic findings of COVID-19 admitted patients, the predictors of mortality in the second wave, and clinical outcomes in the three waves in relation to COVAXIN vaccination status.

MATERIAL AND METHODS: This was a serial three-round retrospective study from the electronic medical records using multistage random sampling where we collected and critically analyzed the demographic, and all the relevant possible health data of the cases that consist of 514 cases admitted in three waves. The data from death certificates among the 555 cases in the second wave have been analyzed to conclude predictors of mortality.

RESULTS: Mortality increased with age, male gender, comorbidities, and raised C-reactive protein level. High NL ratio, extent of pulmonary involvement. There was a wide variation in incidence and spectrum of illness starting from 79% incidence of mild symptomatic in the initial and third wave, but remained in the range of 35-65% in the second wave, respectively, and the most noticeable symptomatic illness was that of the upper respiratory tract. In fulminant cases, the mode of presentations was severe pneumonia and acute respiratory distress syndrome. Males were more sufferers than females. Children had better outcomes compared to adults. COVID-associated coagulopathy had a normal platelet count. Subsequently, in 2021 year onwards vaccination of the vulnerable population was launched in a phased manner that changed the dynamics of the disease outcome by better survival chances despite intercurrent COVID infection by induction of herd immunity. On the contrary, there was a higher prevalence of serious illness among non-vaccinated individuals. While the cases continued during the second wave of the pandemic, long COVID became a clinical entity of symptomatic that persisted or recurred among the COVID illness recovered cases after reverse transcriptase polymerase chain reaction results for COVID-19 became negative. The symptoms consisted of fatigue, cough, dyspnea as pulmonary manifestations and extra-pulmonary involvement of the cardiac, renal, and central nervous systems and the pulmonary imaging features consisted of interstitial pneumonia, consolidation, cavity pattern, and prone to microbial infection. These events lead to morbidity and admission. Coinciding with the vaccination of all population of Odisha province with the first dose of the vaccine by around the period of the first quarter of 2022, there was a new variant named Omicron responsible in the third wave, in which the majority of the admitted cases had.mild upper respiratory illness. This was not as lethal as its predecessors due to its lower propensity to invade the lungs and blood vessels.

CONCLUSION: Immune dysregulation plays a central role in the pathogenesis of the manifestations. Vaccine-induced protection and the induction of herd immunity played a proactive role in the waning of the severity of clinical presentations.}, } @article {pmid37446047, year = {2023}, author = {Ailioaie, LM and Ailioaie, C and Litscher, G}, title = {Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37446047}, issn = {1422-0067}, mesh = {*Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Quality of Life ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Dysbiosis/complications ; Disease Progression ; Inflammation ; Adolescent ; SARS-CoV-2 ; }, abstract = {For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.}, } @article {pmid37445634, year = {2023}, author = {Tsilingiris, D and Vallianou, NG and Karampela, I and Christodoulatos, GS and Papavasileiou, G and Petropoulou, D and Magkos, F and Dalamaga, M}, title = {Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445634}, issn = {1422-0067}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Acute-Phase Proteins ; Biomarkers ; Inflammation ; }, abstract = {Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.}, } @article {pmid37445426, year = {2023}, author = {Fernández-de-Las-Peñas, C and Ortega-Santiago, R and Cancela-Cilleruelo, I and Rodríguez-Jiménez, J and Fuensalida-Novo, S and Martín-Guerrero, JD and Pellicer-Valero, ÓJ and Cigarán-Méndez, M}, title = {Prevalence of Self-Reported Anosmia and Ageusia in Elderly Patients Who Had Been Previously Hospitalized by SARS-CoV-2: The LONG-COVID-EXP Multicenter Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {13}, pages = {}, pmid = {37445426}, issn = {2077-0383}, support = {Recursos REACT-UE del Programa Operativo de Madrid 2014-2020, en la línea de actuación de proyectos de I+D+i en materia de respuesta a COVID 19 (LONG-COVID-EXP-CM)//Fondo Europeo De Desarrollo Regional -/ ; }, abstract = {We explored two different graph methods for visualizing the prevalence of self-reported post-COVID anosmia and ageusia in a large sample of individuals who had been previously hospitalized in five different hospitals. A cohort of 1266 previously hospitalized COVID-19 survivors participated. Participants were assessed at hospitalization (T0) and at three different follow-up periods: 8.4 (T1), 13.2 (T2), and 18.3 (T3) months after hospital discharge. They were asked about the presence of self-reported anosmia and ageusia that they attributed to infection. Anosmia was defined as a self-perceived feeling of complete loss of smell. Ageusia was defined as a self-perceived feeling of complete loss of taste. Data about hospitalization were recorded from medical records. The results revealed that the prevalence of anosmia decreased from 8.29% (n = 105) at hospitalization (T0), to 4.47% (n = 56) at T1, to 3.27% (n = 41) at T2, and 3.35% (n = 42) at T3. Similarly, the prevalence of ageusia was 7.10% (n = 89) at the onset of SARS-CoV-2 infection (T0), but decreased to 3.03% (n = 38) at T1, to 1.99% (n = 25) at T2, and 1.36% (n = 17) at T3. The Sankey plots showed that only 10 (0.8%) and 11 (0.88%) patients exhibited anosmia and ageusia throughout all the follow-ups. The exponential curves revealed a progressive decrease in prevalence, demonstrating that self-reported anosmia and ageusia improved in the years following hospitalization. The female sex (OR4.254, 95% CI 1.184-15.294) and sufferers of asthma (OR7.086, 95% CI 1.359-36.936) were factors associated with the development of anosmia at T2, whereas internal care unit admission was a protective factor (OR0.891, 95% CI 0.819-0.970) for developing anosmia at T2. The use of a graphical method, such as a Sankey plot, shows that post-COVID self-reported anosmia and ageusia exhibit fluctuations during the first years after SARS-CoV-2 infection. Additionally, self-reported anosmia and ageusia also show a decrease in prevalence during the first years after infection, as expressed by exponential bar plots. The female sex was associated with the development of post-COVID anosmia, but not ageusia, in our cohort of elderly patients previously hospitalized due to COVID-19.}, } @article {pmid37445382, year = {2023}, author = {Wernhart, S and Weihe, E and Totzeck, M and Balcer, B and Rassaf, T and Luedike, P}, title = {Cardiopulmonary Profiling of Athletes with Post-Exertional Malaise after COVID-19 Infection-A Single-Center Experience.}, journal = {Journal of clinical medicine}, volume = {12}, number = {13}, pages = {}, pmid = {37445382}, issn = {2077-0383}, abstract = {(1) Background: Cardiopulmonary exercise testing (CPET) has been suggested by the European Society of Cardiology (ESC) for assessing the exercise limitations of apparently healthy individuals, but data on elite athletes regarding this test are scarce. (2) Methods: We analyzed CPET in elite (n = 43, 21.9 ± 3.7 years) and recreational (n = 40, 34.7 ± 13.0 years) athletes with persistent subjective exercise intolerance and post-exertional malaise (PEM) after COVID-19 infection. The primary outcome was the point prevalence of the adequate cardiopulmonary response (ACPR), defined by the presence of all of the following ESC criteria for apparently healthy individuals: (1) >100% of predicted peak oxygen consumption (predVO2peak), (2) VE/VCO2 < 30, (3) no exercise oscillatory ventilation (EOV), and (4) heart rate recovery of ≥12 beats/minute 1 min after exercise termination (HRR1). Results: ACPR occurred more frequently in elite athletes than in recreational athletes (70.0% vs. 39.5%; p = 0.005), mainly driven by the lower VE/VCO2 (<30: 97.7% vs. 65%, p < 0.001). Elite (11.6%) and recreational athletes (22.5%) showing a plateau of O2 pulse did not display ACPR. Conclusions: ACPR was not observed in all recreational and elite athletes with PEM. In particular, perturbed VE/VCO2 and the plateauing of O2 pulse are suitable for quantifying exercise limitations and may identify a high-risk population with long-COVID-19 syndrome who require their training intensities to be adapted.}, } @article {pmid37445359, year = {2023}, author = {da Silva, MRT and Costa, AP and da Luz, AA and Pelaio, CH and Cruz, FB and Steil, GF and Giamberardino, HIG and Prando, C}, title = {From Acute Phase to Long COVID: A Cross-Sectional Study of the Epidemiological Profile and Clinical Evaluation of SARS-CoV-2 Infection in Employees at a Pediatric Hospital.}, journal = {Journal of clinical medicine}, volume = {12}, number = {13}, pages = {}, pmid = {37445359}, issn = {2077-0383}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic began in Brazil on 26 February 2020. By 6 May 2023, 37.4 million cases had been confirmed, causing 701 thousand deaths in the country. We aimed to describe the epidemiological profile and clinical development of COVID-19 cases among the employees of a health institution, from acute infection to long COVID.

METHODS: This was a longitudinal study using a retrospective and prospective approach via questionnaires referring to epidemiological investigation, which was the inclusion criteria, and about long-term symptoms.

RESULTS: A total of 809 employees were detected with SARS-CoV-2 infection via RT-PCR, 466 of them answered the epidemiological investigation, and 101 completed the Long COVID Symptom Questionnaire. The most commonly affected employees were women (88.6%) working in patient care (68.6%). Headache, myalgia, cough, odynophagia, and runny nose were the most frequent symptoms. Only three employees (0.6%) required hospitalization, while the other employees required outpatient management due to mild symptoms. We identified 19 (4.1%) cases of reinfection, and 42 (41.6%) employees reported long-term symptoms, such as myalgia, dyspnea, and headache.

CONCLUSIONS: Although most cases were mild with good outcomes, long COVID cases identified are noteworthy, as these symptoms may impact quality of life even months after SARS-CoV-2 infection.}, } @article {pmid37445257, year = {2023}, author = {Rodríguez-Pérez, MP and Sánchez-Herrera-Baeza, P and Rodríguez-Ledo, P and Huertas-Hoyas, E and Fernández-Gómez, G and Montes-Montes, R and Pérez-de-Heredia-Torres, M}, title = {Influence of Clinical and Sociodemographic Variables on Health-Related Quality of Life in the Adult Population with Long COVID.}, journal = {Journal of clinical medicine}, volume = {12}, number = {13}, pages = {}, pmid = {37445257}, issn = {2077-0383}, abstract = {Worldwide, about 10 percent of patients affected by long COVID require appropriate follow-up and intervention. The main objective of this study was to analyze the long-term impact of mild long COVID in the adult population, and to determine the effect of clinical and sociodemographic variables on health-related quality of life in those affected. Methods: A cross-sectional descriptive study of a sample of Spanish adult patients with persistent COVID-19 symptoms at least three months after diagnosis. Data collection took place between April and July 2021. The health-related quality of life of the sample was low, with worse results in the physical component summary (PCS) 24.66 (SD = 4.45) compared to the mental component summary (MCS) 45.95 (SD = 8.65). The multi-regression analysis showed significant differences by sex in the dimensions of physical functioning (p = 0.040); bodily pain (p = 0.036); and health transition (p = 0.018). Additionally, a longer time since infection had a significant effect on physical functioning (p = 0.039); general health (p = 0.037); vitality (p = 0.034); and general health transition (p = 0.002). The effect of occupational imbalance was significant for all dimensions. Conclusions: people with long COVID have a reduced quality of life. Sex, time since infection, and occupational imbalance are predictors of a worse quality of life.}, } @article {pmid37444803, year = {2023}, author = {Estebanez-Pérez, MJ and Martín-Valero, R and Vinolo-Gil, MJ and Pastora-Bernal, JM}, title = {Effectiveness of Digital Physiotherapy Practice Compared to Usual Care in Long COVID Patients: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {13}, pages = {}, pmid = {37444803}, issn = {2227-9032}, abstract = {Long COVID syndrome has been recognized as a public health problem. Digital physiotherapy practice is an alternative that can better meet the needs of patients. The aim of this review was to synthesize the evidence of digital physiotherapy practice in Long COVID patients. A systematic review was carried out until December 2022. The review was complemented by an assessment of the risk of bias and methodological quality. A narrative synthesis of results was conducted, including subgroup analyses by intervention and clinical outcomes. Six articles, including 540 participants, were selected. Five articles were considered of high enough methodological quality. Parallel-group, single-blind, randomized controlled trials were the most commonly used research design. Tele-supervised home-based exercise training was the most commonly used intervention. Great heterogeneity in clinical outcomes and measurement tools was found. A subgroup analysis showed that digital physiotherapy is effective in improving clinical outcomes. Significant differences in favor of digital interventions over usual care were reported. Nevertheless, discrepancies regarding effectiveness were found. Improvements in clinical outcomes with digital physiotherapy were found to be at least non-inferior to usual care. This review provides new evidence that digital physiotherapy practice is an appropriate intervention for Long COVID patients, despite the inherent limitations of the review. Registration: CRD42022379004.}, } @article {pmid37444079, year = {2023}, author = {Bonham, C and Juarez, R and Siegal, N}, title = {Long COVID and Unemployment in Hawaii.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {13}, pages = {}, pmid = {37444079}, issn = {1660-4601}, support = {OT2 HD108105/HD/NICHD NIH HHS/United States ; U54 GM138062/GM/NIGMS NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Unemployment ; Employment ; Post-Acute COVID-19 Syndrome ; Hawaii/epidemiology ; *COVID-19/epidemiology ; }, abstract = {The state of Hawaii has seen 390,000 COVID-19 cases and nearly 1900 deaths since the start of the pandemic. Although the negative impact of the pandemic on employment has been widely documented, this paper demonstrates that those who were infected and suffer from lingering symptoms (i.e., long COVID) had different employment outcomes than those who did not experience such symptoms. Using data from our longitudinal cohort in the state of Hawaii, we found that those who reported long COVID in May 2022 were 6.43% more likely to be unemployed at the time of the May survey and 7.07% more likely in November 2022. In addition, we showed that vaccination is associated with higher rates of employment; each additional vaccine an individual received by May decreased the likelihood of unemployment by 6.9% in May and 3.9% in November. Further, individuals who reported more severe symptoms of long COVID were 6.36% less likely to be employed in May and 5.75% less likely to be employed in November. Our results suggest that vaccination policies and policies aimed at preventing contraction and accommodating individuals with long COVID may be effective measures for mitigating the adverse effects of the pandemic on employment.}, } @article {pmid37443983, year = {2023}, author = {Packer, RMA and Brand, CL and Belshaw, Z and Pegram, CL and Dale, F and Stevens, KB and O'Neill, DG}, title = {Is UK Puppy Purchasing Suffering a Long COVID Effect? Ongoing Negative Impacts of the COVID-19 Pandemic upon Puppy Purchase Motivations and Behaviours in 2021.}, journal = {Animals : an open access journal from MDPI}, volume = {13}, number = {13}, pages = {}, pmid = {37443983}, issn = {2076-2615}, support = {RVC 2021//Research England Quality-related Research Strategic Priorities Fund/ ; AWF_2020_14_RP//Animal Welfare Foundation/ ; }, abstract = {The COVID-19 pandemic led to a surge in acquisitions of puppies in the UK, dubbed the "Pandemic Puppy" phenomenon. In addition to an increased demand for puppies, widespread changes to both why and how puppies were purchased during this period compared to pre-pandemic 2019 purchases were documented, many of which threatened canine welfare (e.g., puppies being collected away from their place of birth, without seeing their mother). This study aimed to explore which changes to the pre-purchase and purchase motivations and behaviours of UK owners who purchased a puppy aged <16 weeks in the 2020 phase of the COVID-19 pandemic had persisted into 2021 or had returned to pre-pandemic 2019 levels. An online survey was conducted during February to April 2022 from which 2080 valid responses were analysed ("2021 puppies") and compared with previously collected data from comparable cohorts in 2019 (n = 1148, "2019 puppies") and 2020 (n = 4369, "Pandemic Puppies"). While the majority of the peak pandemic changes documented in 2020 had returned to their 2019 pre-pandemic baseline, others persisted into 2021. Multinomial logistic regression models revealed that the shifts during 2020 towards owners viewing their puppy pre-purchase over video calls or via video recordings/photos rather than in-person and towards collecting their puppy from outside of their breeders' property rather than inside had persisted into 2021 and had not returned to pre-pandemic levels. Year-on-year significant rises in the number of puppies sold with a passport were documented between 2019 and 2021, with over 1 in 10 2021 puppies having been sold with a passport, the figure more than doubling since 2019. An increasing number of these puppies sold with a passport were under the minimum legal age for import at sale. Going forward, these concerning changes require further monitoring and human behaviour change interventions to tackle, including increased buyer awareness but also legislative approaches to prevent the greatest harm.}, } @article {pmid37443565, year = {2023}, author = {Halfmann, MC and Luetkens, JA and Langenbach, IL and Kravchenko, D and Wenzel, P and Emrich, T and Isaak, A}, title = {Cardiac MRI Findings in Patients Clinically Referred for Evaluation of Post-Acute Sequelae of SARS-CoV-2 Infection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {37443565}, issn = {2075-4418}, abstract = {Persistent or recurrent cardiovascular symptoms have been identified as one of the hallmarks of long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The purpose of this study was to determine the prevalence and extent of cardiac abnormalities in patients referred for cardiac MRI due to clinical evidence of PASC. To investigate this, two tertiary care hospitals identified all patients who were referred for cardiac MRI under the suspicion of PASC in a 2-year period and retrospectively included them in this study. Patients with previously known cardiac diseases were excluded. This resulted in a total cohort of 129 patients (63, 51% female; age 41 ± 16 years). The majority of patients (57%) showed normal cardiac results. No patient had active myocarditis or an acute myocardial infarction. However, 30% of patients had evidence of non-ischemic myocardial fibrosis, which exceeds the prevalence in the normal adult population and suggests that a possible history of myocarditis might explain persistent symptoms in the PASC setting.}, } @article {pmid37443561, year = {2023}, author = {Telser, J and Grossmann, K and Weideli, OC and Hillmann, D and Aeschbacher, S and Wohlwend, N and Velez, L and Kuhle, J and Maleska, A and Benkert, P and Risch, C and Conen, D and Risch, M and Risch, L}, title = {Concentrations of Serum Brain Injury Biomarkers Following SARS-CoV-2 Infection in Individuals with and without Long-COVID-Results from the Prospective Population-Based COVI-GAPP Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {13}, pages = {}, pmid = {37443561}, issn = {2075-4418}, support = {101005177//Innovative Medicines Initiative/ ; na//The Government of the Principality of Liechtenstein/ ; na//The Princely House of the Principality of Liechtenstein/ ; na//The Hanela Foundation in Switzerland/ ; }, abstract = {It is unknown whether neurological symptoms are associated with brain injury after SARS-CoV-2 infections and whether brain injury and related symptoms also emerge in Long-COVID patients. Biomarkers such as serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) can be used to elucidate neuro-axonal and astroglial injuries. We investigated whether these biomarkers are associated with COVID-19 infection status, associated symptoms and Long-COVID. From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, sNfL and sGFAP were measured before, during and after (five and ten months) the infection. Individual symptoms and Long-COVID status were assessed using questionnaires. Neurological associated symptoms were described for individuals after a mild and moderate COVID-19 infection; however, sNfL (p = 0.74) and sGFAP (p = 0.24) did not change and were not associated with headache (p = 0.51), fatigue (p = 0.93), anosmia (p = 0.77) or ageusia (p = 0.47). In Long-COVID patients, sGFAP (p = 0.038), but not sNfL (p = 0.58), significantly increased but was not associated with neurological associated symptoms. Long-COVID status, but not post-acute SARS-CoV-2 infections, may be associated with astroglial injury/activation, even if neurological associated symptoms were not correlated.}, } @article {pmid37443263, year = {2023}, author = {Matsumoto, C and , }, title = {Reply to: Microvascular hypertensive disease, long COVID, and end-organ pathology.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {9}, pages = {2249-2250}, pmid = {37443263}, issn = {1348-4214}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Hypertension/physiopathology ; }, } @article {pmid37443258, year = {2023}, author = {Cimolai, N}, title = {Microvascular hypertensive disease, Long COVID, and end-organ pathology.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {9}, pages = {2247-2248}, pmid = {37443258}, issn = {1348-4214}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Hypertension ; }, } @article {pmid37442375, year = {2023}, author = {Feelisch, M and Clark, AD and Cumpstey, AF and Santolini, J and Jackson, AA}, title = {Long COVID: Potential role of the Reactive Species Interactome.}, journal = {The Journal of infection}, volume = {87}, number = {3}, pages = {280-281}, doi = {10.1016/j.jinf.2023.07.004}, pmid = {37442375}, issn = {1532-2742}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37442195, year = {2023}, author = {Polese, J and Ramos, AD and Moulaz, IR and Sant'Ana, L and Lacerda, BSP and Soares, CES and Lança, KEM and Thompson, BP and Júnior, GPB and Polese Pinto, II and Mill, JG}, title = {Pulmonary function and exercise capacity six months after hospital discharge of patients with severe COVID-19.}, journal = {The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases}, volume = {27}, number = {4}, pages = {102789}, pmid = {37442195}, issn = {1678-4391}, mesh = {Male ; Humans ; Adult ; Middle Aged ; *Patient Discharge ; Exercise Tolerance ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Hospitals ; }, abstract = {INTRODUCTION: The long-term consequences of COVID-19, especially pulmonary impairment, are frequent but not well understood. The knowledge about sequels or long COVID-19 are necessary, considering the high prevalence and need for specific public strategies.

METHOD: The study was conducted to evaluate symptoms (standardized questionnaire), pulmonary function (spirometry), and exercise capacity (6-minute-walk-test) at 30 (D30), 90 (D90), and 180 (D180) days after hospital discharge of patients surviving to severe COVID-19. We excluded in this follow up patients with comorbidities before COVID infection.

RESULTS: 44 patients were included and 31 (26 men) completed the 6-month follow-up (age mean 53.6 ± 9.6 years). At D180, 28% presented still at least one symptom. The most common was dyspnea (17.2%), followed by cough (13.8%), and myalgia (10.3%). All spirometric parameters showed progressive improvement from D30 to D180. However, 16% maintained a restrictive pattern on spirometry test, 44% presented desaturation on the 6-minute walk-test, and 25% walked < 75% of the predicted value.

CONCLUSION: 6-months after hospital discharge, reduced pulmonary function and reduced exercise capacity was founded frequently and more than a quarter remained symptomatic. The persistent symptoms and functional impairment suggest that sequels and development of Long COVID-19 are very common. The identification of these patients to provide the necessary health care is a challenging task, considering the large number of patients infected and surviving to COVID-19 disease.}, } @article {pmid37441066, year = {2023}, author = {Calvier, L and Drelich, A and Hsu, J and Tseng, CT and Mina, Y and Nath, A and Kounnas, MZ and Herz, J}, title = {Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1185748}, pmid = {37441066}, issn = {1664-3224}, support = {R01 NS093382/NS/NINDS NIH HHS/United States ; R37 HL063762/HL/NHLBI NIH HHS/United States ; RF1 AG053391/AG/NIA NIH HHS/United States ; }, mesh = {Mice ; Animals ; Humans ; *COVID-19 ; Intercellular Adhesion Molecule-1 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Chemokine CCL4 ; Chemokine CXCL10 ; Interleukin-4 ; Inflammation ; }, abstract = {Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a hyperinflammatory state, as judged by increased concentration of cytokines (IL-1α, IL-4, IL-6, IL-10 and IL-17A), chemokines (IP-10 and MIP-1β), and adhesion markers (E-selectin and ICAM-1). Reelin level was correlated with IL-1α, IL-4, IP-10, MIP-1β, and ICAM-1, suggesting a specific role for Reelin in COVID-19 progression. Furthermore, Reelin and all of the inflammatory markers aforementioned returned to normal in a long COVID cohort, showing that the hyperinflammatory state was resolved. Finally, we tested Reelin inhibition with the anti-Reelin antibody CR-50 in hACE2 transgenic mice infected with SARS-CoV-2. CR-50 prophylactic treatment decreased mortality and disease severity in this model. These results demonstrate a direct proinflammatory function for Reelin in COVID-19 and identify it as a drug target. This work opens translational clinical applications in severe SARS-CoV-2 infection and beyond in auto-inflammatory diseases.}, } @article {pmid37440739, year = {2023}, author = {Latimer, KM and Gunther, A and Kopec, M}, title = {Fatigue in Adults: Evaluation and Management.}, journal = {American family physician}, volume = {108}, number = {1}, pages = {58-69}, pmid = {37440739}, issn = {1532-0650}, mesh = {Humans ; Adult ; *Fatigue Syndrome, Chronic/diagnosis/therapy/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise/physiology ; }, abstract = {Fatigue is among the top 10 reasons patients visit primary care offices, and it significantly affects patients' well-being and occupational safety. A comprehensive history and cardiopulmonary, neurologic, and skin examinations help guide the workup and diagnosis. Fatigue can be classified as physiologic, secondary, or chronic. Physiologic fatigue can be addressed by proper sleep hygiene, a healthy diet, and balancing energy expenditure. Secondary fatigue is improved by treating the underlying condition. Cognitive behavior therapy, exercise therapy, and acupuncture may help with some of the fatigue associated with chronic conditions. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, severe, and potentially debilitating disorder with demonstrated inflammatory, neurologic, immunologic, and metabolic abnormalities. ME/CFS has a poor prognosis, with no proven treatment or cure. It may become more common after the COVID-19 pandemic because many patients with long COVID (post-COVID-19 condition) have symptoms similar to ME/CFS. The most important symptom of ME/CFS is postexertional malaise. The 2015 National Academy of Medicine diagnostic criteria diagnose ME/CFS. Exercise can be harmful to patients with ME/CFS because it can trigger postexertional malaise. Patients should be educated about pacing their activity not to exceed their limited energy capacity. Treatment should prioritize comorbidities and symptoms based on severity.}, } @article {pmid37438797, year = {2023}, author = {Nguyen, LH and Okin, D and Drew, DA and Battista, VM and Jesudasen, SJ and Kuntz, TM and Bhosle, A and Thompson, KN and Reinicke, T and Lo, CH and Woo, JE and Caraballo, A and Berra, L and Vieira, J and Huang, CY and Das Adhikari, U and Kim, M and Sui, HY and Magicheva-Gupta, M and McIver, L and Goldberg, MB and Kwon, DS and Huttenhower, C and Chan, AT and Lai, PS}, title = {Metagenomic assessment of gut microbial communities and risk of severe COVID-19.}, journal = {Genome medicine}, volume = {15}, number = {1}, pages = {49}, pmid = {37438797}, issn = {1756-994X}, support = {K01 DK120742/DK/NIDDK NIH HHS/United States ; K23 DK125838/DK/NIDDK NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; T32 HL116275/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Microbiota ; Metagenome ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure.

METHODS: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites.

RESULTS: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease.

CONCLUSIONS: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.}, } @article {pmid37437953, year = {2023}, author = {Rotar Pavlic, D and Maksuti, A and Mihevc, M and Munda, A and Medija, K and Strauch, V}, title = {Long COVID as a never-ending puzzle: the experience of primary care physicians. A qualitative interview study.}, journal = {BJGP open}, volume = {7}, number = {4}, pages = {}, pmid = {37437953}, issn = {2398-3795}, abstract = {BACKGROUND: Long COVID provides a new context in which primary health care needs to be re-examined, especially because it has health and social dimensions. Primary care physicians' experiences and perceptions of caring for patients with long COVID are an underexplored area.

AIM: To explore the experiences of Slovenian primary care physicians in management and treatment of patients with long COVID.

DESIGN & SETTING: A qualitative interview study of physicians in Slovenian primary care.

METHOD: Semi-structured interviews were held with physicians who had treated patients with long COVID until saturation was reached. The interviews were carried out between November 2021 and April 2022. Qualitative content analysis (QCA) was used to analyse the data collected.

RESULTS: Seventeen participants were interviewed. The following five categories were defined based on the coding process: the definition and symptoms of long COVID; social exclusion; sick leave and returning to the work environment; cooperation with rehabilitation centres; and the importance of trust and good communication with the patient.

CONCLUSION: The study showed the experiences of Slovenian primary care physicians in the management and treatment of long COVID. The problems related to long COVID were divided into two groups: health problems and psychosocial problems. Slovenian physicians have the greatest problems with dealing with the patient's ability to work. It was found that adequate communication and trust between physicians and patients are two important indicators for an integrated model of managing long COVID.}, } @article {pmid37437914, year = {2023}, author = {Kelly, JD and Curteis, T and Rawal, A and Murton, M and Clark, LJ and Jafry, Z and Shah-Gupta, R and Berry, M and Espinueva, A and Chen, L and Abdelghany, M and Sweeney, DA and Quint, JK}, title = {SARS-CoV-2 post-acute sequelae in previously hospitalised patients: systematic literature review and meta-analysis.}, journal = {European respiratory review : an official journal of the European Respiratory Society}, volume = {32}, number = {169}, pages = {}, pmid = {37437914}, issn = {1600-0617}, support = {K23 AI146268/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Disease Progression ; Dyspnea ; }, abstract = {BACKGROUND: Many individuals hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience post-acute sequelae of SARS-CoV-2 infection (PASC), sometimes referred to as "long COVID". Our objective was to conduct a systematic literature review and meta-analysis to identify PASC-associated symptoms in previously hospitalised patients and determine the frequency and temporal nature of PASC.

METHODS: Searches of MEDLINE, Embase, Cochrane Library (2019-2021), World Health Organization International Clinical Trials Registry Platform and reference lists were performed from November to December 2021. Articles were assessed by two reviewers against eligibility criteria and a risk of bias tool. Symptom data were synthesised by random effects meta-analyses.

RESULTS: Of 6942 records, 52 studies with at least 100 patients were analysed; ∼70% were Europe-based studies. Most data were from the first wave of the pandemic. PASC symptoms were analysed from 28 days after hospital discharge. At 1-4 months post-acute SARS-CoV-2 infection, the most frequent individual symptoms were fatigue (29.3% (95% CI 20.1-40.6%)) and dyspnoea (19.6% (95% CI 12.8-28.7%)). Many patients experienced at least one symptom at 4-8 months (73.1% (95% CI 44.2-90.3%)) and 8-12 months (75.0% (95% CI 56.4-87.4%)).

CONCLUSIONS: A wide spectrum of persistent PASC-associated symptoms were reported over the 1-year follow-up period in a significant proportion of participants. Further research is needed to better define PASC duration and determine whether factors such as disease severity, vaccination and treatments have an impact on PASC.}, } @article {pmid37434760, year = {2023}, author = {Day, H and Yellman, B and Hammer, S and Rond, C and Bell, J and Abbaszadeh, S and Stoddard, G and Unutmaz, D and Bateman, L and Vernon, SD}, title = {Cognitive impairment in post-acute sequelae of COVID-19 and short duration myalgic encephalomyelitis patients is mediated by orthostatic hemodynamic changes.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1203514}, pmid = {37434760}, issn = {1662-4548}, support = {U54 NS105539/NS/NINDS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; }, abstract = {INTRODUCTION: Cognitive impairment is experienced by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of COVID-19 (PASC). Patients report difficulty remembering, concentrating, and making decisions. Our objective was to determine whether orthostatic hemodynamic changes were causally linked to cognitive impairment in these diseases.

METHODS: This prospective, observational cohort study enrolled PASC, ME/CFS, and healthy controls. All participants underwent clinical evaluation and assessment that included brief cognitive testing before and after an orthostatic challenge. Cognitive testing measured cognitive efficiency which is defined as the speed and accuracy of subject's total correct responses per minute. General linear mixed models were used to analyze hemodynamics and cognitive efficiency during the orthostatic challenge. Additionally, mediation analysis was used to determine if hemodynamic instability induced during the orthostatic challenge mediated the relationship between disease status and cognitive impairment.

RESULTS: Of the 276 participants enrolled, 256 were included in this study (34 PASC, 71 < 4 year duration ME/CFS, 69 > 10 year ME/CFS duration, and 82 healthy controls). Compared to healthy controls, the disease cohorts had significantly lower cognitive efficiency scores immediately following the orthostatic challenge. Cognitive efficiency remained low for the >10 year ME/CFS 2 and 7 days after orthostatic challenge. Narrow pulse pressure less than 25% of systolic pressure occurred at 4 and 5 min into the orthostatic challenge for the PASC and ME/CFS cohorts, respectively. Abnormally narrow pulse pressure was associated with slowed information processing in PASC patients compared to healthy controls (-1.5, p = 0.04). Furthermore, increased heart rate during the orthostatic challenge was associated with a decreased procedural reaction time in PASC and < 4 year ME/CFS patients who were 40 to 65 years of age.

DISCUSSION: For PASC patients, both their disease state and hemodynamic changes during orthostatic challenge were associated with slower reaction time and decreased response accuracy during cognitive testing. Reduced cognitive efficiency in <4 year ME/CFS patients was associated with higher heart rate in response to orthostatic stress. Hemodynamic changes did not correlate with cognitive impairment for >10 year ME/CFS patients, but cognitive impairment remained. These findings underscore the need for early diagnosis to mitigate direct hemodynamic and other physiological effects on symptoms of cognitive impairment.}, } @article {pmid37434574, year = {2023}, author = {Van Den Bossche, MJA and Van den Bulcke, L and Peeters, AM and Van Vré, ATE}, title = {[Long COVID: oude uitdagingen, nieuwe kansen].}, journal = {Tijdschrift voor psychiatrie}, volume = {65}, number = {6}, pages = {354-355}, pmid = {37434574}, issn = {0303-7339}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37434573, year = {2023}, author = {Everaerd, DS and Biere-Rafi, S}, title = {[Neuropsychiatric aspects of long COVID].}, journal = {Tijdschrift voor psychiatrie}, volume = {65}, number = {6}, pages = {347-353}, pmid = {37434573}, issn = {0303-7339}, mesh = {Humans ; Female ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Anxiety ; Anxiety Disorders ; Hospitalization ; }, abstract = {BACKGROUND: Persistent symptoms after COVID-19 are a global problem, and it is becoming increasingly clear that they include neuropsychiatric symptoms.

AIM: To provide an overview of current knowledge on clinical presentation, risk factors, prevention and treatment of neuropsychiatric symptoms and disorders after COVID-19.

METHOD: PRISMA literature search.

RESULTS: Anxiety, depression and posttraumatic stress symptoms are common after COVID-19. Cognitive symptoms are also very common and appear to be persistent, while data on risk factors to develop these symptoms is scarce. Women and patients after ICU admission, delirium or with somatic comorbidities have a higher risk of developing post COVID psychiatric symptoms. Vaccination may have a protective effect. Furthermore, there is a lack of evidence on effective treatment strategies for COVID-19-related neurocognitive symptoms.

CONCLUSION: More research on risk factors, identification and especially effective treatment options for neuropsychiatric symptoms after COVID-19 is needed. In the meantime, guidelines on disorders with a similar clinical presentation could potentially play a role in the diagnosis and treatment of persistent neuropsychiatric symptoms after COVID-19.}, } @article {pmid37434526, year = {2023}, author = {Saad-Roy, CM and Levin, SA and Grenfell, BT and Boots, M}, title = {Epidemiological impacts of post-infection mortality.}, journal = {Proceedings. Biological sciences}, volume = {290}, number = {2002}, pages = {20230343}, pmid = {37434526}, issn = {1471-2954}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/mortality ; Epidemics ; }, abstract = {Infectious diseases may cause some long-term damage to their host, leading to elevated mortality even after recovery. Mortality due to complications from so-called 'long COVID' is a stark illustration of this potential, but the impacts of such post-infection mortality (PIM) on epidemic dynamics are not known. Using an epidemiological model that incorporates PIM, we examine the importance of this effect. We find that in contrast to mortality during infection, PIM can induce epidemic cycling. The effect is due to interference between elevated mortality and reinfection through the previously infected susceptible pool. In particular, robust immunity (via decreased susceptibility to reinfection) reduces the likelihood of cycling; on the other hand, disease-induced mortality can interact with weak PIM to generate periodicity. In the absence of PIM, we prove that the unique endemic equilibrium is stable and therefore our key result is that PIM is an overlooked phenomenon that is likely to be destabilizing. Overall, given potentially widespread effects, our findings highlight the importance of characterizing heterogeneity in susceptibility (via both PIM and robustness of host immunity) for accurate epidemiological predictions. In particular, for diseases without robust immunity, such as SARS-CoV-2, PIM may underlie complex epidemiological dynamics especially in the context of seasonal forcing.}, } @article {pmid37434326, year = {2023}, author = {Krishna, B and Wills, M and Sithole, N}, title = {Long COVID: what is known and what gaps need to be addressed.}, journal = {British medical bulletin}, volume = {147}, number = {1}, pages = {6-19}, pmid = {37434326}, issn = {1471-8391}, support = {G112259/DH_/Department of Health/United Kingdom ; 225023/Z/22/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Disease Progression ; Fatigue/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID is a chronic condition that follows after acute COVID-19 and is characterized by a wide range of persistent, cyclic symptoms.

SOURCES OF DATA: PubMed search for publications featuring 'Long COVID' or 'post-acute sequelae of COVID-19'.

AREAS OF AGREEMENT: Long COVID occurs frequently post-acute COVID-19, with a majority of people experiencing at least one symptom (such as cough, fatigue, myalgia, anosmia and dyspnoea) 4 weeks after infection.

AREAS OF CONTROVERSY: The specific symptoms and the minimum duration of symptoms required to be defined as Long COVID.

GROWING POINTS: There is a consistent reduction in Long COVID incidence amongst vaccinated individuals, although the extent of this effect remains unclear.

There is an urgent need to understand the causes of Long COVID, especially extreme fatigue more than 6 months after infection. We must understand who is at risk and whether reinfections similarly risk Long COVID.}, } @article {pmid37434321, year = {2023}, author = {White, P and Abbey, S and Angus, B and Ball, HA and Buchwald, DS and Burness, C and Carson, AJ and Chalder, T and Clauw, DJ and Coebergh, J and David, AS and Dworetzky, BA and Edwards, MJ and Espay, AJ and Etherington, J and Fink, P and Flottorp, S and Garcin, B and Garner, P and Glasziou, P and Hamilton, W and Henningsen, P and Hoeritzauer, I and Husain, M and Huys, AML and Knoop, H and Kroenke, K and Lehn, A and Levenson, JL and Little, P and Lloyd, A and Madan, I and van der Meer, JWM and Miller, A and Murphy, M and Nazareth, I and Perez, DL and Phillips, W and Reuber, M and Rief, W and Santhouse, A and Serranova, T and Sharpe, M and Stanton, B and Stewart, DE and Stone, J and Tinazzi, M and Wade, DT and Wessely, SC and Wyller, V and Zeman, A}, title = {Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {94}, number = {12}, pages = {1056-1063}, doi = {10.1136/jnnp-2022-330463}, pmid = {37434321}, issn = {1468-330X}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; Surveys and Questionnaires ; Exercise Therapy ; *Cognitive Behavioral Therapy ; }, abstract = {Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.}, } @article {pmid37433988, year = {2023}, author = {Altmann, DM and Whettlock, EM and Liu, S and Arachchillage, DJ and Boyton, RJ}, title = {The immunology of long COVID.}, journal = {Nature reviews. Immunology}, volume = {23}, number = {10}, pages = {618-634}, pmid = {37433988}, issn = {1474-1741}, support = {MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/DH_/Department of Health/United Kingdom ; LT2-027/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; }, abstract = {Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing-remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.}, } @article {pmid37433943, year = {2023}, author = {Ledford, H}, title = {Gene linked to long COVID found in analysis of thousands of patients.}, journal = {Nature}, volume = {619}, number = {7970}, pages = {445}, pmid = {37433943}, issn = {1476-4687}, mesh = {Humans ; *Genetic Predisposition to Disease/genetics ; *Post-Acute COVID-19 Syndrome/genetics/virology ; SARS-CoV-2/pathogenicity ; }, } @article {pmid37433819, year = {2023}, author = {Kim, Y and Bae, S and Chang, HH and Kim, SW}, title = {Long COVID prevalence and impact on quality of life 2 years after acute COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11207}, pmid = {37433819}, issn = {2045-2322}, mesh = {Quality of Life ; Reinfection ; Prospective Studies ; Humans ; COVID-19 Vaccines ; Prevalence ; *COVID-19/epidemiology ; Adult ; *Post-Acute COVID-19 Syndrome ; }, abstract = {There has been an increasing interest in the long-term impact of long COVID. However, only a few studies have investigated the clinical manifestations of long COVID after 24 months of acute infection. In this study, prospective online surveys were conducted in adults previously diagnosed with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13, 2020, at 6, 12, and 24 months after COVID-19. We investigated self-reported symptoms and the EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys. After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis. Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%), insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the incidence of long COVID at 24 months in terms of the number of vaccinations received. Although the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants. Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time, and COVID-19 vaccination or the number of vaccinations received may not significantly affect the incidence of long COVID.}, } @article {pmid37433720, year = {2023}, author = {Genecand, L and Altarelli, M and Binkova, A and Loew, S and Vaudan, S and Gex, G and Bridevaux, PO and Frésard, I}, title = {Dysfunctional breathing symptoms, functional impact and quality of life in patients with long COVID-19: a prospective case series.}, journal = {BMJ open respiratory research}, volume = {10}, number = {1}, pages = {}, pmid = {37433720}, issn = {2052-4439}, mesh = {Humans ; *Quality of Life ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Respiration ; }, abstract = {BACKGROUND: Dysfunctional breathing is increasingly recognised after SARS-CoV-2 infection, but the associated symptoms, functional impact and quality of life have not been systematically studied.

METHODS: This study describes a prospective case series of 48 patients with dysfunctional breathing based on compatible symptoms and an abnormal breathing pattern during cardiopulmonary exercise testing. Patients with underlying disease that could explain these symptoms were excluded. Median time from COVID-19 to evaluation was 212 (IQR 121) days. Self-administered questionnaires, including the Nijmegen questionnaire, Short-Form (36) Health Survey (SF-36), Hospital Anxiety and Depression Scale, modified Medical Research Council scale, post-COVID-19 Functional Scale, and specific long COVID symptoms, were the outcome measures.

RESULTS: On average, mean V'O2 was preserved. Pulmonary function tests were within limits of normality. Hyperventilation, periodic deep sighs/erratic breathing and mixed types of dysfunctional breathing were diagnosed in 20.8%, 47.1% and 33.3% of patients, respectively. After dyspnoea, the five most frequent symptoms using the Nijmegen scale with a cut-off of ≥3 were faster/deeper breathing (75.6%), palpitations (63.8%), sighs (48.7%), unable to breathe deeply (46.3%) and yawning (46.2%). Median Nijmegen and Hospital Anxiety and Depression Scale scores were 28 (IQR 20) and 16.5 (IQR 11), respectively. SF-36 scores were lower than the reference value.

CONCLUSIONS: Long COVID patients with dysfunctional breathing have a high burden of symptoms, functional impact and a low quality of life, despite no or negligible organic damage.}, } @article {pmid37429788, year = {2023}, author = {Chong, I and Roth, JA and Hug, BL}, title = {Prevalence and characteristics of post COVID-19 condition five months after SARS-COV-2 infection in inpatients and outpatients.}, journal = {European journal of internal medicine}, volume = {116}, number = {}, pages = {137-140}, doi = {10.1016/j.ejim.2023.07.002}, pmid = {37429788}, issn = {1879-0828}, mesh = {Humans ; *Inpatients ; Outpatients ; Prevalence ; *COVID-19 ; SARS-CoV-2 ; }, } @article {pmid37429685, year = {2023}, author = {Russell, L and Jeffreys, M and Churchward, M and Cumming, J and McKenzie, F and O'Loughlin, C and Asiasiga, L and Bell, R and Hickey, H and Irurzun-Lopez, M and Kamau, L and Kokaua, J and McDonald, J and McFarland-Tautau, M and Smiler, K and Uia, T and Vaka, S and Veukiso-Ulugia, A and Wong, C and Ellison Loschmann, L}, title = {Cohort profile: Ngā Kawekawe o Mate Korona | Impacts of COVID-19 in Aotearoa - a prospective, national cohort study of people with COVID-19 in New Zealand.}, journal = {BMJ open}, volume = {13}, number = {7}, pages = {e071083}, pmid = {37429685}, issn = {2044-6055}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Maori People ; New Zealand/epidemiology ; Pandemics ; Prospective Studies ; }, abstract = {PURPOSE: The COVID-19 pandemic has had significant health, social and economic impacts around the world. We established a national, population-based longitudinal cohort to investigate the immediate and longer-term physical, psychological and economic impacts of COVID-19 on affected people in Aotearoa New Zealand (Aotearoa), with the resulting evidence to assist in designing appropriate health and well-being services for people with COVID-19.

PARTICIPANTS: All people residing in Aotearoa aged 16 years or over, who had a confirmed or probable diagnosis of COVID-19 prior to December 2021, were invited to participate. Those living in dementia units were excluded. Participation involved taking part in one or more of four online surveys and/or in-depth interviews. The first wave of data collection took place from February to June 2022.

FINDINGS TO DATE: By 30 November 2021, of 8735 people in Aotearoa aged 16+ who had COVID-19, 8712 were eligible for the study and 8012 had valid addresses so were able to be contacted to take part. A total of 990 people, including 161 Tāngata Whenua (Māori, Indigenous peoples of Aotearoa) completed one or more surveys; in addition, 62 took part in in-depth interviews. Two hundred and seventeen people (20%) reported symptoms consistent with long COVID. Key areas of adverse impacts were experiences of stigma, mental distress, poor experiences of health services and barriers to healthcare, each being significantly more pronounced among disabled people and/or those with long COVID.

FUTURE PLANS: Further data collection is planned to follow-up cohort participants. This cohort will be supplemented by the inclusion of a cohort of people with long COVID following Omicron infection. Future follow-ups will assess longitudinal changes to health and well-being impacts, including mental health, social, workplace/education and economic impacts of COVID-19.}, } @article {pmid37427773, year = {2023}, author = {Perumal, R and Shunmugam, L and Naidoo, K}, title = {Long COVID: An approach to clinical assessment and management in primary care.}, journal = {South African family practice : official journal of the South African Academy of Family Practice/Primary Care}, volume = {65}, number = {1}, pages = {e1-e10}, pmid = {37427773}, issn = {2078-6204}, support = {MC_PC_16022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/diagnosis/epidemiology/therapy ; Public Health ; Primary Health Care ; }, abstract = {Long COVID is an emerging public health threat, following swiftly behind the surges of acute infection over the course of the COVID-19 pandemic. It is estimated that there are already approximately 100 million people suffering from Long COVID globally, 0.5 million of whom are South African, and for whom our incomplete understanding of the condition has forestalled appropriate diagnosis and clinical care. There are several leading postulates for the complex, multi-mechanistic pathogenesis of Long COVID. Patients with Long COVID may present with a diversity of clinical phenotypes, often with significant overlap, which may exhibit temporal heterogeneity and evolution. Post-acute care follow-up, targeted screening, diagnosis, a broad initial assessment and more directed subsequent assessments are necessary at the primary care level. Symptomatic treatment, self-management and rehabilitation are the mainstays of clinical care for Long COVID. However, evidence-based pharmacological interventions for the prevention and treatment of Long COVID are beginning to emerge. This article presents a rational approach for assessing and managing patients with Long COVID in the primary care setting.}, } @article {pmid37426952, year = {2023}, author = {Gottlieb, M and Spatz, ES and Yu, H and Wisk, LE and Elmore, JG and Gentile, NL and Hill, M and Huebinger, RM and Idris, AH and Kean, ER and Koo, K and Li, SX and McDonald, S and Montoy, JCC and Nichol, G and O'Laughlin, KN and Plumb, ID and Rising, KL and Santangelo, M and Saydah, S and Wang, RC and Venkatesh, A and Stephens, KA and Weinstein, RA and , }, title = {Long COVID Clinical Phenotypes up to 6 Months After Infection Identified by Latent Class Analysis of Self-Reported Symptoms.}, journal = {Open forum infectious diseases}, volume = {10}, number = {7}, pages = {ofad277}, pmid = {37426952}, issn = {2328-8957}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection.

METHODS: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms.

RESULTS: Among 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months.

CONCLUSIONS: We identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.}, } @article {pmid37425897, year = {2023}, author = {Liu, Z and Hollmann, C and Kalanidhi, S and Grothey, A and Keating, S and Mena-Palomo, I and Lamer, S and Schlosser, A and Kaiping, A and Scheller, C and Sotzny, F and Horn, A and Nürnberger, C and Cejka, V and Afshar, B and Bahmer, T and Schreiber, S and Vehreschild, JJ and Miljukov, O and Schäfer, C and Kretzler, L and Keil, T and Reese, JP and Eichner, FA and Schmidbauer, L and Heuschmann, PU and Störk, S and Morbach, C and Riemekasten, G and Beyersdorf, N and Scheibenbogen, C and Naviaux, RK and Williams, M and Ariza, ME and Prusty, BK}, title = {Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37425897}, support = {R01 AI084898/AI/NIAID NIH HHS/United States ; }, abstract = {Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.}, } @article {pmid37425374, year = {2023}, author = {Shen, Q and Mikkelsen, DH and Luitva, LB and Song, H and Kasela, S and Aspelund, T and Bergstedt, J and Lu, Y and Sullivan, PF and Ye, W and Fall, K and Tornvall, P and Pawitan, Y and Andreassen, OA and Buil, A and Milani, L and Fang, F and Valdimarsdóttir, U}, title = {Psychiatric disorders and subsequent risk of cardiovascular disease: a longitudinal matched cohort study across three countries.}, journal = {EClinicalMedicine}, volume = {61}, number = {}, pages = {102063}, pmid = {37425374}, issn = {2589-5370}, support = {R01 MH123724/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown.

METHODS: In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively.

FINDINGS: During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort.

INTERPRETATION: Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders.

FUNDING: This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.}, } @article {pmid37425014, year = {2023}, author = {Barnden, L and Thapaliya, K and Eaton-Fitch, N and Barth, M and Marshall-Gradisnik, S}, title = {Altered brain connectivity in Long Covid during cognitive exertion: a pilot study.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1182607}, pmid = {37425014}, issn = {1662-4548}, abstract = {INTRODUCTION: Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection.

METHODS: Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippocampus and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores.

RESULTS: Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI.

DISCUSSION: Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep-wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.}, } @article {pmid37422499, year = {2023}, author = {Miyata, Y and Suzuki, K and Nagano, T and Iida, K and Hasegawa, T and Uga, H and Matsuoka, H}, title = {Cellular immunity reflects the persistent symptoms among COVID-19 recovered patients in Japan.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11071}, pmid = {37422499}, issn = {2045-2322}, mesh = {Humans ; *Vascular Endothelial Growth Factor A ; Retrospective Studies ; Japan/epidemiology ; Ligands ; *COVID-19 ; Immunity, Cellular ; Interleukin-6 ; }, abstract = {Coronavirus disease (COVID-19) often causes persistent symptoms long after infection, referred to as "long COVID" or post-acute COVID-19 syndrome (PACS). This phenomenon has been studied primarily concerning B-cell immunity, while the involvement of T-cell immunity is still unclear. This retrospective study aimed to examine the relationship among the number of symptoms, cytokine levels, and the Enzyme-linked immunosorbent spot (ELISPOT) assay data in patients with COVID-19. To examine inflammatory conditions, plasma interleukin (IL)-6, IL-10, IL-18, chemokine ligand 9 (CXCL9), chemokine ligand 3 (CCL3), and vascular endothelial growth factor (VEGF) levels were analyzed using plasma obtained from COVID-19 recovery patients and healthy controls (HC). These levels were significantly higher in the COVID-19 group than those in the HC group. ELISPOT assays were performed to investigate the correlation between COVID-19 persistent symptoms and T-cell immunity. Cluster analysis of ELISPOT categorized COVID-19 recovery patients in the ELISPOT-high and -low groups, based on the values of S1, S2, and N. The number of persistent symptoms was significantly higher in the ELISPOT-low group than those in the ELISPOT-high group. Thus, T cell immunity is critical for the rapid elimination of COVID-19 persistent symptoms, and its measurement immediately after COVID-19 recovery might predict long-term COVID-19 or PACS.}, } @article {pmid37419540, year = {2023}, author = {Barshikar, S and Laguerre, M and Gordon, P and Lopez, M}, title = {Integrated Care Models for Long Coronavirus Disease.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {689-700}, pmid = {37419540}, issn = {1558-1381}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Consensus ; *Physical and Rehabilitation Medicine ; SARS-CoV-2 ; *Delivery of Health Care, Integrated ; Disease Progression ; }, abstract = {Professional or governmental agencies and organizations have developed guidelines to define the problem and evaluate and manage patients with Post-Acute Sequelae of SARS CoV-2 (PASC). Multidisciplinary models largely exist in academic centers and larger cities; however, most care for PASC patients is provided by the primary care providers. The American Academy of Physical Medicine and Rehabilitation has been in the forefront in releasing consensus statements as a part of the long COVID collaborative.}, } @article {pmid37419539, year = {2023}, author = {Estores, IM and Ackerman, P}, title = {Integrative Medicine in Long COVID.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {677-688}, doi = {10.1016/j.pmr.2023.03.006}, pmid = {37419539}, issn = {1558-1381}, mesh = {Humans ; United States ; Post-Acute COVID-19 Syndrome ; *Integrative Medicine/methods ; *COVID-19 ; *Complementary Therapies/methods ; }, abstract = {Physiatry and Integrative Medicine practice approaches the care of patients holistically to achieve recovery and optimal function. The current lack of knowledge on proven treatments for long COVID has resulted in a surge in both demand and use of complementary and integrative health (CIH) treatments. This overview summarizes CIH therapies using the framework of the United States National Center for Complementary and Integrative Health, divided into nutritional, psychological, physical, and combinations of these categories. Representative therapies selected based on the availability of published and ongoing research for post-COVID conditions are described.}, } @article {pmid37419538, year = {2023}, author = {Katz, NB and Hunter, TL and Flores, LE and Silver, JK}, title = {Addressing Rehabilitation Health Care Disparities During the Coronavirus Disease-2019 Pandemic and Beyond.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {657-675}, pmid = {37419538}, issn = {1558-1381}, mesh = {Humans ; Child ; *COVID-19/epidemiology ; Ethnicity ; Healthcare Disparities ; SARS-CoV-2 ; Pandemics ; Minority Groups ; Health Services Accessibility ; }, abstract = {The coronavirus disease-2019 pandemic exposed and expanded upon preexisting health care disparities. Individuals with disabilities and those who identify with racial/ethnic minority groups have been disproportionately adversely impacted. These inequities are likely present in the proportions of individuals impacted by post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection requiring specialized rehabilitation. Specific populations including, but not limited to pregnant, pediatric, and older individuals, may also necessitate tailored medical care during acute infection and beyond. Telemedicine may reduce the care gap. Further research and clinical guidance are needed to provide equitable, culturally competent, and individualized care to these historically or socially marginalized and underrepresented populations.}, } @article {pmid37419537, year = {2023}, author = {Chen, EY and Burton, JM and Johnston, A and Morrow, AK and Yonts, AB and Malone, LA}, title = {Considerations in Children and Adolescents Related to Coronavirus Disease 2019 (COVID-19).}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {643-655}, pmid = {37419537}, issn = {1558-1381}, support = {P50 HD103538/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Adolescent ; Child ; *COVID-19 ; SARS-CoV-2 ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Life Style ; Disease Progression ; }, abstract = {Pediatric post-acute sequelae of SARS-CoV-2 (PASC) or "long COVID" are a complex multisystemic disease that affects children's physical, social, and mental health. PASC has a variable presentation, time course, and severity and can affect children even with mild or asymptomatic acute COVID-19 symptoms. Screening for PASC in children with a history of SARS-CoV-2 infection is important for early detection and intervention. A multifaceted treatment approach and utilization of multidisciplinary care, if available, are beneficial in managing the complexities of PASC. Lifestyle interventions, physical rehabilitation, and mental health management are important treatment approaches to improve pediatric PASC patients' quality of life.}, } @article {pmid37419535, year = {2023}, author = {Abbott, Z and Summers, W and Niehaus, W}, title = {Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {607-621}, pmid = {37419535}, issn = {1558-1381}, mesh = {Humans ; *COVID-19 ; Quality of Life ; Fatigue/etiology ; }, abstract = {Fatigue from post-acute sequelae of coronavirus disease 2019 is a complex constellation of symptoms that could be driven by a wide spectrum of underlying etiologies. Despite this, there seems to be hope for treatment plans that focus on addressing possible etiologies and creating a path to improving quality of life and a paced return to activity.}, } @article {pmid37419534, year = {2023}, author = {Copley, M and Kozminski, B and Gentile, N and Geyer, R and Friedly, J}, title = {Postacute Sequelae of SARS-CoV-2: Musculoskeletal Conditions and Pain.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {585-605}, pmid = {37419534}, issn = {1558-1381}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; *Musculoskeletal Diseases/diagnosis/etiology ; Pain ; Post-Acute COVID-19 Syndrome ; }, abstract = {Musculoskeletal and pain sequelae of COVID-19 are common in both the acute infection and patients experiencing longer term symptoms associated with recovery, known as postacute sequelae of COVID-19 (PASC). Patients with PASC may experience multiple manifestations of pain and other concurrent symptoms that complicate their experience of pain. In this review, the authors explore what is currently known about PASC-related pain and its pathophysiology as well as strategies for diagnosis and management.}, } @article {pmid37419529, year = {2023}, author = {Hunter, TL and Sarno, DL and Jumreornvong, O and Esparza, R and Flores, LE and Silver, JK}, title = {The Role of Surgical Prehabilitation During the COVID-19 Pandemic and Beyond.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {523-538}, pmid = {37419529}, issn = {1558-1381}, mesh = {Humans ; Aged ; *Frailty ; Frail Elderly ; Preoperative Exercise ; Ethnicity ; Pandemics ; *COVID-19/epidemiology ; Minority Groups ; }, abstract = {The challenging circumstances of the COVID-19 pandemic caused a regression in baseline health of disadvantaged populations, including individuals with frail syndrome, older age, disability, and racial-ethnic minority status. These patients often have more comorbidities and are associated with increased risk of poor postoperative complications, hospital readmissions, longer length of stay, nonhome discharges, poor patient satisfaction, and mortality. There is critical need to advance frailty assessments to improve preoperative health in older populations. Establishing a gold standard for measuring frailty will improve identification of vulnerable, older patients, and subsequently direct designs for population-specific, multimodal prehabilitation to reduce postoperative morbidity and mortality.}, } @article {pmid37419527, year = {2023}, author = {Tabacof, L and Nicolau, E and Rivera, A and Putrino, D}, title = {Post-COVID Conditions and Burden of Disease.}, journal = {Physical medicine and rehabilitation clinics of North America}, volume = {34}, number = {3}, pages = {499-511}, doi = {10.1016/j.pmr.2023.04.007}, pmid = {37419527}, issn = {1558-1381}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cost of Illness ; }, abstract = {Post-COVID condition (PCC), also known as long COVID, is a multi-systemic illness estimated to affect 10% to 20% of those infected, regardless of age, baseline health status, or initial symptom severity. PCC has affected millions of lives, with long-lasting debilitating effects, but unfortunately it remains an underrecognized and therefore poorly documented condition. Defining and disseminating the burden of PCC is essential for developing effective public health strategies to address this issue in the long term.}, } @article {pmid37419426, year = {2023}, author = {Viskupicova, J and Rezbarikova, P and Kovacikova, L and Kandarova, H and Majekova, M}, title = {Inhibitors of SARS-CoV-2 main protease: Biological efficacy and toxicity aspects.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {92}, number = {}, pages = {105640}, doi = {10.1016/j.tiv.2023.105640}, pmid = {37419426}, issn = {1879-3177}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Antiviral Agents/pharmacology ; Molecular Docking Simulation ; }, abstract = {The emergence of the highly contagious respiratory disease, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a significant global public health concern. To combat this virus, researchers have focused on developing antiviral strategies that target specific viral components, such as the main protease (M[pro]), which plays a crucial role in SARS-CoV-2 replication. While many compounds have been identified as potent inhibitors of M[pro], only a few have been translated into clinical use due to the potential risk-benefit trade-offs. Development of systemic inflammatory response and bacterial co-infection in patients belong to severe, frequent complications of COVID-19. In this context, we analysed available data on the anti-inflammatory and antibacterial activities of the SARS-CoV-2 M[pro] inhibitors for possible implementation in the treatment of complicated and long COVID-19 cases. Synthetic feasibility and ADME properties were calculated and included for better characterisation of the compounds' predicted toxicity. Analysis of the collected data resulted in several clusters pointing to the most prospective compounds for further study and design. The complete tables with collected data are attached in Supplementary material for use by other researchers.}, } @article {pmid37418949, year = {2023}, author = {Mankelow, J and Ravindran, D and Graham, A and Suri, S and Pate, JW and Ryan, CG and Martin, D}, title = {An evaluation of a one-day pain science education event in a high school setting targeting pain related beliefs, knowledge, and behavioural intentions.}, journal = {Musculoskeletal science & practice}, volume = {66}, number = {}, pages = {102818}, doi = {10.1016/j.msksp.2023.102818}, pmid = {37418949}, issn = {2468-7812}, mesh = {Adult ; Humans ; Female ; Adolescent ; Male ; *Intention ; Schools ; Educational Status ; Exercise ; *Chronic Pain/therapy ; }, abstract = {BACKGROUND: Persistent pain is a common condition affecting one in four UK adults. Public understanding of pain is limited. Delivering pain education within schools may improve public understanding in the longer term.

OBJECTIVE: To evaluate the impact of a one-day Pain Science Education (PSE) event on sixth form/high school students' pain beliefs, knowledge and behavioural intention.

METHODS: Exploratory, single-site, mixed-methods, single-arm study involving secondary school students ≥16 years old attending a one-day PSE event. Outcome measures included the Pain Beliefs Questionnaire (PBQ), Concepts of Pain Inventory (COPI-ADULT), a vignette to assess pain behaviours; and thematic analysis of semi-structured interviews.

RESULTS: Ninety (mean age 16.5 years, 74% female) of the 114 attendees, agreed to participate in the evaluation. PBQ scores improved on the Organic beliefs subscale [mean difference -5.9 (95% CI -6.8, -5.0), P < 0.01] and Psychosocial Beliefs subscale [1.6 (1.0, 2.2) P < 0.01]. The COPI-Adult revealed an improvement [7.1 (6.0-8.1) points, P < 0.01] between baseline and post intervention. Pain behavioural intentions improved post education for work, exercise, and bed rest related activities (p < 0.05). Thematic analysis of interviews (n = 3) identified increased awareness of chronic pain and its underpinning biology, beliefs that pain education should be widely available, and that pain management should be holistic.

CONCLUSIONS: A one-day PSE public health event can improve pain beliefs, knowledge and behavioural intentions in high school students and increase openness to holistic management. Future controlled studies are needed to confirm these results and investigate potential long-term impacts.}, } @article {pmid37418268, year = {2023}, author = {Katz, GM and Bach, K and Bobos, P and Cheung, A and Décary, S and Goulding, S and Herridge, MS and McNaughton, CD and Palmer, KS and Razak, FA and Zhang, B and Quinn, KL}, title = {Understanding How Post-COVID-19 Condition Affects Adults and Health Care Systems.}, journal = {JAMA health forum}, volume = {4}, number = {7}, pages = {e231933}, doi = {10.1001/jamahealthforum.2023.1933}, pmid = {37418268}, issn = {2689-0186}, mesh = {Humans ; Adult ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Delivery of Health Care ; }, abstract = {IMPORTANCE: Post-COVID-19 condition (PCC), also known as long COVID, encompasses the range of symptoms and sequelae that affect many people with prior SARS-CoV-2 infection. Understanding the functional, health, and economic effects of PCC is important in determining how health care systems may optimally deliver care to individuals with PCC.

OBSERVATIONS: A rapid review of the literature showed that PCC and the effects of hospitalization for severe and critical illness may limit a person's ability to perform day-to-day activities and employment, increase their risk of incident health conditions and use of primary and short-term health care services, and have a negative association with household financial stability. Care pathways that integrate primary care, rehabilitation services, and specialized assessment clinics are being developed to support the health care needs of people with PCC. However, comparative studies to determine optimal care models based on their effectiveness and costs remain limited. The effects of PCC are likely to have large-scale associations with health systems and economies and will require substantial investment in research, clinical care, and health policy to mitigate these effects.

CONCLUSIONS AND RELEVANCE: An accurate understanding of additional health care and economic needs at the individual and health system levels is critical to informing health care resource and policy planning, including identification of optimal care pathways to support people affected by PCC.}, } @article {pmid37415915, year = {2023}, author = {Juby, AG and Cunnane, SC and Mager, DR}, title = {Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1126534}, pmid = {37415915}, issn = {2296-861X}, abstract = {COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction ("brain fog") precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using [18]F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer's disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.}, } @article {pmid37415777, year = {2023}, author = {Matias-Guiu, JA and Díez-Cirarda, M}, title = {Are there cognitive and neuroimaging signatures in long COVID?.}, journal = {Brain communications}, volume = {5}, number = {4}, pages = {fcad189}, pmid = {37415777}, issn = {2632-1297}, abstract = {This scientific commentary refers to 'Markers of limbic system damage following SARS-CoV-2 infection', by Thomasson et al. (https://doi.org/10.1093/braincomms/fcad177).}, } @article {pmid37415689, year = {2023}, author = {Marchi, M and Grenzi, P and Serafini, V and Capoccia, F and Rossi, F and Marrino, P and Pingani, L and Galeazzi, GM and Ferrari, S}, title = {Psychiatric symptoms in Long-COVID patients: a systematic review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1138389}, pmid = {37415689}, issn = {1664-0640}, abstract = {OBJECTIVE: People who have been infected by COVID-19 showing persistent symptoms after 4 weeks from recovery are thought to suffer from Long-COVID syndrome (LC). There is uncertainty on the clinical manifestations of LC. We undertook a systematic review to summarize the available evidence about the main psychiatric manifestations of LC.

METHOD: PubMed (Medline), Scopus, CINHAL, PsycINFO, and EMBASE were searched until May 2022. Studies reporting estimation of emerging psychiatric symptoms and/or psychiatric diagnoses among adult people with LC were included. Pooled prevalence for each psychiatric condition was calculated in absence of control groups to compare with.

RESULTS: Thirty-three reports were included in the final selection, corresponding to 282,711 participants with LC. After 4 weeks from COVID-19 infection recovery, participants reported the following psychiatric symptoms: depression, anxiety, post-traumatic symptoms (PTS), cognitive and sleeping disturbances (i.e., insomnia or hypersomnia). The most common psychiatric manifestation resulted to be sleep disturbances, followed by depression, PTS, anxiety, and cognitive impairment (i.e., attention and memory deficits). However, some estimates were affected by important outlier effect played by one study. If study weight was not considered, the most reported condition was anxiety.

CONCLUSIONS: LC may have non-specific psychiatric manifestations. More research is needed to better define LC and to differentiate it from other post-infectious or post-hospitalization syndromes.

PROSPERO (CRD42022299408).}, } @article {pmid37415256, year = {2023}, author = {Samper-Pardo, M and Formento-Marín, N and Oliván-Blázquez, B and León-Herrera, S and Benedé-Azagra, B}, title = {Use of community resources as health assets for rehabilitation of people with Long COVID in northeastern Spain two years after the outbreak of the COVID-19 pandemic: qualitative study.}, journal = {Archives of public health = Archives belges de sante publique}, volume = {81}, number = {1}, pages = {125}, pmid = {37415256}, issn = {0778-7367}, support = {PI21/01356//Instituto de Salud Carlos III/ ; PI21/01356//Instituto de Salud Carlos III/ ; }, abstract = {INTRODUCTION: The epidemiology of Post COVID Condition is not yet known. There are different treatment options, but they are not recommended or suitable for all those affected. For this reason and due to the lack of health treatment, many of these patients have tried to carry out their own rehabilitation through the use of community resources.

OBJECTIVE: The objective of this study is to deepen into the understanding about the use of community resources as assets for health and rehabilitation by people with Long COVID and their utility.

METHODOLOGY: A qualitative design was carried out with the participation of 35 Long COVID patients, of which 17 subjects were interviewed individually and 18 of them were part of two focus groups. The participating patients were recruited in November and December 2021 from the Primary Health Care centers and through the Association of Long COVID patients of Aragon. The research topics were the use of community resources, before and after their infection by COVID-19, rehabilitation through their use, as well as barriers and strengths for their employment. All analyses were performed iteratively using NVivo software.

RESULTS: Long COVID patients who have used community resources for rehabilitation have seen an improvement in their physical and mental health. Most of them, specifically those affected, have used green spaces, public facilities, physical or cultural activities and associations. The main barriers identified have been the symptoms themselves and the fear of reinfection, with the main advantage of these activities being the perceived health benefits.

CONCLUSION: The use of community resources seems to be beneficial in the recovery process of Long COVID patients, so it is necessary to continue delving into this topic and promote the formal use of the Recommendation of Health Assets from Primary healthcare.}, } @article {pmid37414856, year = {2023}, author = {Holm, H and Ivarsdottir, EV and Olafsdottir, T and Thorolfsdottir, R and Eythorsson, E and Norland, K and Gisladottir, R and Jonsdottir, G and Unnsteinsdottir, U and Sveinsdottir, KE and Jonsson, BA and Andresdottir, M and Arnar, DO and Arnthorsson, AO and Birgisdottir, K and Bjarnadottir, K and Bjarnadottir, S and Bjornsdottir, G and Einarsson, G and Eiriksdottir, B and Gardarsdottir, EE and Gislason, T and Gottfredsson, M and Gudmundsdottir, S and Gudmundsson, J and Gunnarsdottir, K and Helgadottir, A and Helgason, D and Hinriksdottir, I and Ingvarsson, RF and Jonasdottir, SS and Jonsdottir, I and Karlsdottir, TH and Kristinsdottir, AM and Kristinsson, SY and Kristjansdottir, S and Love, TJ and Ludviksdottir, D and Masson, G and Norddahl, G and Olafsdottir, T and Olafsson, I and Rafnar, T and Runolfsdottir, HL and Saemundsdottir, J and Sigurbjornsson, S and Sigurdardottir, K and Sigurdsson, E and Sigurdsson, MI and Sigurdsson, EL and Steinthorsdottir, V and Sveinbjornsson, G and Thorarensen, EA and Thorbjornsson, B and Thorsteinsdottir, B and Tragante, V and Ulfarsson, MO and Stefansson, H and Gislason, T and Kristjansson, M and Palsson, R and Sulem, P and Thorsteinsdottir, U and Thorgeirsson, G and Gudbjartsson, DF and Stefansson, K}, title = {Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.}, journal = {Communications medicine}, volume = {3}, number = {1}, pages = {94}, pmid = {37414856}, issn = {2730-664X}, abstract = {BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear.

METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection.

RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection.

CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.}, } @article {pmid37414647, year = {2023}, author = {Fernández-de-Las-Peñas, C}, title = {One year later: Prevalence of long-COVID symptoms.}, journal = {European journal of internal medicine}, volume = {115}, number = {}, pages = {37-38}, doi = {10.1016/j.ejim.2023.07.001}, pmid = {37414647}, issn = {1879-0828}, mesh = {Humans ; Prevalence ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37410793, year = {2023}, author = {Lou, S and Yang, M and Li, T and Zhao, W and Cevasco, H and Yang, YT and Gerstein, M}, title = {Constructing a full, multiple-layer interactome for SARS-CoV-2 in the context of lung disease: Linking the virus with human genes and microbes.}, journal = {PLoS computational biology}, volume = {19}, number = {7}, pages = {e1011222}, pmid = {37410793}, issn = {1553-7358}, support = {R01 DA051906/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2/genetics ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; *MicroRNAs/genetics ; }, abstract = {The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in millions of deaths worldwide. The disease presents with various manifestations that can vary in severity and long-term outcomes. Previous efforts have contributed to the development of effective strategies for treatment and prevention by uncovering the mechanism of viral infection. We now know all the direct protein-protein interactions that occur during the lifecycle of SARS-CoV-2 infection, but it is critical to move beyond these known interactions to a comprehensive understanding of the "full interactome" of SARS-CoV-2 infection, which incorporates human microRNAs (miRNAs), additional human protein-coding genes, and exogenous microbes. Potentially, this will help in developing new drugs to treat COVID-19, differentiating the nuances of long COVID, and identifying histopathological signatures in SARS-CoV-2-infected organs. To construct the full interactome, we developed a statistical modeling approach called MLCrosstalk (multiple-layer crosstalk) based on latent Dirichlet allocation. MLCrosstalk integrates data from multiple sources, including microbes, human protein-coding genes, miRNAs, and human protein-protein interactions. It constructs "topics" that group SARS-CoV-2 with genes and microbes based on similar patterns of co-occurrence across patient samples. We use these topics to infer linkages between SARS-CoV-2 and protein-coding genes, miRNAs, and microbes. We then refine these initial linkages using network propagation to contextualize them within a larger framework of network and pathway structures. Using MLCrosstalk, we identified genes in the IL1-processing and VEGFA-VEGFR2 pathways that are linked to SARS-CoV-2. We also found that Rothia mucilaginosa and Prevotella melaninogenica are positively and negatively correlated with SARS-CoV-2 abundance, a finding corroborated by analysis of single-cell sequencing data.}, } @article {pmid37407214, year = {2023}, author = {Duwel, V and de Kort, JML and Becker, CM and Kock, SM and Tromp, GG and Busari, JO}, title = {A Cross-Sectional Study of the Physical and Mental Well-Being of Long COVID Patients in Aruba.}, journal = {Clinical medicine & research}, volume = {21}, number = {2}, pages = {69-78}, pmid = {37407214}, issn = {1554-6179}, mesh = {Adult ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Quality of Life ; Aruba ; COVID-19 Testing ; Retrospective Studies ; *COVID-19/epidemiology ; Dyspnea ; Fatigue/diagnosis/epidemiology ; }, abstract = {Objective: To investigate the pattern and prevalence of persistent symptoms of Post-COVID-19 Syndrome (PCS) at 3, 6, 9, and 18 months after discharge. Associated risk factors were further examined to potentially explain the persistence of these symptoms.Design and Setting: A cross-sectional cohort study was conducted at the primary health care facility of Aruba, Dr. Horacio E. Oduber Hospital (HOH).Participants: Inclusion criteria were adults hospitalized at HOH for at least one night between March and July 2021 and laboratory-confirmed COVID-19 diagnosis. Exclusion criteria were deceased before the follow-up, not able to mobilize before or after discharge, living outside of Aruba or in nursing homes, and patients with psychosis, dementia, or hospitalized due to unrelated diseases.Methods: Eligible and willing participants completed a 20-question survey: a self-reported symptoms questionnaire about symptoms during and after COVID-19 infection, level of dyspnea measurement (mMRC-scale), quality of life measurement (EQ-5D-5E with EuroQoL VAS), and mental well-being (WHO-5). Hospitalization related data were gathered via retrospective analysis of patient records. Chi-square test, logistic regression, and ANOVA analyses were conducted; P<0.05 was chosen as level of statistical significance for all analyses.Results: In total, 222 (34.5%) patients were eligible, consenting, and completed the survey. Most participants were interviewed a year or more after their initial COVID-19 infection. Fatigue (37.8%), new-onset dyspnea (38.7%), hair loss (20.3%), and muscle pain (18.0%) were the most frequently reported symptoms at any time post COVID-19 infection. Female participants were found more likely to experience fatigue (P<0.05, OR 2.135, 95% CI 1.154-3.949) and new-onset dyspnea (P<0.05, OR 2.026 95% CI 1.093-3.756) after initial infection. Participants with one or more respiratory comorbidity were more likely to experience new-onset dyspnea (P<0.05, OR 2.681, 95% CI 1.223-5.873). None of the predictor variables was associated with cognitive impairment.Conclusion: This study identified female sex and respiratory comorbidity as crucial risk factors for PCS. Females were also found to have significantly lower health scores. Female participants were more likely to experience fatigue and dyspnea after COVID-19 infection.}, } @article {pmid37406989, year = {2023}, author = {Yelin, D and Daitch, V and Kalfon, T and Mor, M and Buchrits, S and Shafir, Y and Awwad, M and Ghantous, N and Shapira-Lichter, I and Leibovici, L and Yahav, D and Margalit, I}, title = {Long COVID sexual dysfunction among both genders: Evaluation of a cohort of COVID-19 recoverees.}, journal = {Infectious diseases now}, volume = {53}, number = {7}, pages = {104750}, doi = {10.1016/j.idnow.2023.104750}, pmid = {37406989}, issn = {2666-9919}, abstract = {OBJECTIVES: We aimed to assess Long COVID sexual dysfunction among both sexes.

PATIENTS AND METHODS: A cross-sectional study at a multidisciplinary COVID clinic. Consecutive patients answered a symptom-based questionnaire, which included sexual dysfunction. Individuals reporting any degree of sexual dysfunction were compared with those who denied. A multivariable logistic regression was conducted to identify risk factors. A principal component analysis was implemented to explore other symptoms associated with sexual dysfunction.

RESULTS: All in all, 391 individuals recovering from COVID-19 completed the questionnaire, 211 women and 180 men. Mean age was 45.2 (SD 15.4) years. Most (280, 85.9%) had mild COVID-19, assessed at a median of 3.8 (IQR 2.0) months from diagnosis. Sexual dysfunction was reported by 55 (36%) of the men and 48 (28%) of the women. Increased age [per year; men OR 1.05 (95% CI 1.02-1.08)], long COVID cough [men 2.58 (1.05-6.32)], chest pain [women 3.54 (1.28-9.80)], irritability [women 3.45 (1.28-9.29)], paresthesia [men 4.23 (1.55-10.44); women 3.08 (1.14-8.32)], and emotional distress [men 3.26 (1.36-7.82); women 4.29 (1.65-11.18)] were significantly associated with sexual dysfunction. In women, sexual dysfunction was part of the emotional pattern, while among men, it was part of the emotional and pulmonary patterns.

CONCLUSION: Sexual dysfunction is a common manifestation of long COVID in both men and women. Presence of other long COVID symptoms, and older age, are associated with this phenomenon. Further studies should explore the mechanisms for long COVID sexual dysfunction in both men and women, as well as strategies for prevention and treatment.}, } @article {pmid37406842, year = {2023}, author = {Altmann, CH and Zvonova, E and Richter, L and Schüller, PO}, title = {Pulmonary recovery directly after COVID-19 and in Long-COVID.}, journal = {Respiratory physiology & neurobiology}, volume = {315}, number = {}, pages = {104112}, doi = {10.1016/j.resp.2023.104112}, pmid = {37406842}, issn = {1878-1519}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Respiration ; Combined Modality Therapy ; }, abstract = {Permanent impairment in patients after SARS-CoV-2 infection is frequent, but neither pathophysiology nor mechanisms of the so-called Post-COVID-Syndrome (Long-COVID) are well understood. We present data on pulmonary impairment, pulmonary recovery and outcome comparing patients admitted to a specific COVID-19 rehabilitation program directly after COVID-19 infection with patients long after COVID-19 infection. Diagnostic work up included echocardiography, cardiopulmonary exercise testing and pleural sonography. The rehabilitation program included multimodal respiratory therapy, endurance and resistance muscular training, psychological assistance, and educational measures. Patients in both groups showed similar pulmonary problems. Diaphragm dysfunction was common in both groups. Cardiopulmonary exercise testing showed dysfunctional breathing in most patients of both groups. The specific rehabilitation program applied yielded marked improvements with satisfying pulmonary recovery in both groups. Return to work was possible or expected in most patients. In conclusion, directly after COVID-19 infection as well as in long Covid 4-20 months after COVID-19 dysfunctional breathing patterns in cardiopulmonary exercise testing and diaphragm dysfunction on ultrasound are common and need diagnostic awareness and therapy measures. Specialized rehabilitation programs directly after COVID-19 as well as for Long-COVID patients are effective therapeutic options.}, } @article {pmid37406070, year = {2023}, author = {Ahmed, SS and Adil, PI and Rasheed, NA and Hussein, NR and Dhama, K}, title = {A study of long COVID-19 in Duhok, Kurdistan region, Iraq.}, journal = {Journal of infection in developing countries}, volume = {17}, number = {6}, pages = {805-811}, doi = {10.3855/jidc.17468}, pmid = {37406070}, issn = {1972-2680}, mesh = {Humans ; Male ; Young Adult ; Adult ; Middle Aged ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Iraq/epidemiology ; Cross-Sectional Studies ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Long COVID-19 refers to a range of symptoms and complications that persist after being infected with COVID-19 or develop some time after recovery. Our study aimed at assessing the prevalence of long COVID-19 in Duhok city, Iraq and its correlation with epidemiological and clinical variables.

METHODOLOGY: This cross-sectional study was conducted between March and August 2022. A questionnaire was used for data collection from participants aged 18 and older. The questionnaire included demographic information and clinical data.

RESULTS: Among the 1039 participants, (49.7%) were male with a mean age of 34.048 ± 13 years. Total infected volunteers were 492 (47.4%), out of which 20.7% did not have long COVID-19 and 26.7% had long COVID-19. The most common long COVID-19 manifestations were fatigue (57%), hair loss (39%) and loss/change in the sense of smell or taste (35%). Correlation between the variables gender, comorbidities, age, and duration of infection, and long COVID-19 were significant (p values = 0.016, 0.018, 0.001, and 0.001 respectively).

CONCLUSIONS: There was a significant correlation between long COVID-19 cases and age, gender, comorbidities, and duration of infection. The data of this report can be used as a baseline for studies that may help further understand long COVID-19 sequelae.}, } @article {pmid37405337, year = {2023}, author = {Puntmann, VO and Valbuena-López, S}, title = {ESC Congress 2022 Imaging Highlights.}, journal = {European cardiology}, volume = {18}, number = {}, pages = {e12}, pmid = {37405337}, issn = {1758-3764}, abstract = {Cardiac imaging is an ever-evolving area, with imaging parameters and application in constant re-evaluation. This was reflected in many imaging debates and by the increased number of scientific contributions at the European Society of Cardiology Congress in 2022. While clinical trials tried to answer clinical questions related to the performance of different imaging modalities, many high-quality presentations focused on new imaging biomarkers in different scenarios, such as heart failure with preserved ejection fraction, valvular heart disease or long COVID. This highlights the need for the translation of cardiac imaging technology from research interests towards established measures of clinical practice.}, } @article {pmid37404951, year = {2023}, author = {Woodrow, M and Carey, C and Ziauddeen, N and Thomas, R and Akrami, A and Lutje, V and Greenwood, DC and Alwan, NA}, title = {Systematic Review of the Prevalence of Long COVID.}, journal = {Open forum infectious diseases}, volume = {10}, number = {7}, pages = {ofad233}, pmid = {37404951}, issn = {2328-8957}, abstract = {BACKGROUND: Long COVID occurs in those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability, or pathological changes in adults or children at least 12 weeks postinfection.

METHODS: We searched key registers and databases from January 1, 2020 to November 2, 2021, limited to publications in English and studies with at least 100 participants. Studies in which all participants were critically ill were excluded. Long COVID was extracted as prevalence of at least 1 symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across predefined subgroups (PROSPERO ID CRD42020218351).

RESULTS: One hundred twenty studies in 130 publications were included. Length of follow-up varied between 12 weeks and 12 months. Few studies had low risk of bias. All complete and subgroup analyses except 1 had I[2] ≥90%, with prevalence of persistent symptoms range of 0%-93% (pooled estimate [PE], 42.1%; 95% prediction interval [PI], 6.8% to 87.9%). Studies using routine healthcare records tended to report lower prevalence (PE, 13.6%; PI, 1.2% to 68%) of persistent symptoms/pathology than self-report (PE, 43.9%; PI, 8.2% to 87.2%). However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all 3 (PE, 51.7%; PI, 12.3% to 89.1%). Studies of hospitalized cases had generally higher estimates than community-based studies.

CONCLUSIONS: The way in which Long COVID is defined and measured affects prevalence estimation. Given the widespread nature of SARS-CoV-2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates.}, } @article {pmid37404465, year = {2023}, author = {Mahajan, S and Sen, D and Sunil, A and Srikanth, P and Marathe, SD and Shaw, K and Sahare, M and Galande, S and Abraham, NM}, title = {Knockout of angiotensin converting enzyme-2 receptor leads to morphological aberrations in rodent olfactory centers and dysfunctions associated with sense of smell.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1180868}, pmid = {37404465}, issn = {1662-4548}, support = {IA/I/14/1/501306/WTDBT_/DBT-Wellcome Trust India Alliance/India ; }, abstract = {Neuronal morphological characterization and behavioral phenotyping in mouse models help dissecting neural mechanisms of brain disorders. Olfactory dysfunctions and other cognitive problems were widely reported in asymptomatic carriers and symptomatic patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This led us to generate the knockout mouse model for Angiotensin Converting Enzyme-2 (ACE2) receptor, one of the molecular factors mediating SARS-CoV-2 entry to the central nervous system, using CRISPR-Cas9 based genome editing tools. ACE2 receptors and Transmembrane Serine Protease-2 (TMPRSS2) are widely expressed in the supporting (sustentacular) cells of human and rodent olfactory epithelium, however, not in the olfactory sensory neurons (OSNs). Hence, acute inflammation induced changes due to viral infection in the olfactory epithelium may explain transient changes in olfactory detectabilities. As ACE2 receptors are expressed in different olfactory centers and higher brain areas, we studied the morphological changes in the olfactory epithelium (OE) and olfactory bulb (OB) of ACE2 KO mice in comparison with wild type animals. Our results showed reduced thickness of OSN layer in the OE, and a decrease in cross-sectional area of glomeruli in the OB. Aberrations in the olfactory circuits were revealed by lowered immunoreactivity toward microtubule associated protein 2 (MAP2) in the glomerular layer of ACE2 KO mice. Further, to understand if these morphological alterations lead to compromised sensory and cognitive abilities, we performed an array of behavioral assays probing their olfactory subsystems' performances. ACE2 KO mice exhibited slower learning of odor discriminations at the threshold levels and novel odor identification impairments. Further, ACE2 KO mice failed to memorize the pheromonal locations while trained on a multimodal task implying the aberrations of neural circuits involved in higher cognitive functions. Our results thus provide the morphological basis for the sensory and cognitive disabilities caused by the deletion of ACE2 receptors and offer a potential experimental approach to study the neural circuit mechanisms of cognitive impairments observed in long COVID.}, } @article {pmid37404150, year = {2023}, author = {Bocchino, M and Rea, G and Capitelli, L and Lieto, R and Bruzzese, D}, title = {Chest CT Lung Abnormalities 1 Year after COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Radiology}, volume = {308}, number = {1}, pages = {e230535}, doi = {10.1148/radiol.230535}, pmid = {37404150}, issn = {1527-1315}, mesh = {Adult ; Humans ; *COVID-19/pathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Lung/diagnostic imaging/pathology ; Tomography, X-Ray Computed/methods ; *Bronchiectasis ; *Pulmonary Fibrosis/pathology ; Disease Progression ; }, abstract = {Background Radiological lung sequelae may explain the persistence of respiratory complaints in post-COVID-19 condition (long-COVID). Purpose To perform a systematic review and meta-analysis of the prevalence and type of COVID-19 residual lung abnormalities at 1-year chest CT. Materials and Methods A literature search of PubMed, Web of Science, Embase, and Medline databases was performed from January 2020 to January 2023. Full-text reports of CT lung sequelae in adults (≥18 years) with confirmed COVID-19 at 1-year follow-up were included. The prevalence of any residual lung abnormality and type (fibrotic or not) was analyzed according to the Fleischner Glossary. The meta-analysis included studies with chest CT data assessable in no less than 80% of individuals. A random-effects model was used to estimate pooled prevalence. Multiple sub-group (country, journal category, methodological quality, study setting, outcomes) and meta-regression analyses were performed to identify potential sources of heterogeneity. I[2] statistics estimated low (25%), moderate (26-50%) and high (>50%) heterogeneity. 95% Prediction Intervals (95% PIs) were computed to describe the expected estimates range. Results Of 22 709 records, 21 studies were reviewed (20 prospective, 9 from China, and 7 in radiology journals). The meta-analysis included 14 studies with chest CT data in 1854 of 2043 individuals (M/F: 1109/934). Estimates of lung sequelae were highly heterogeneous (7.1-96.7%), with a pooled frequency of 43.5% (I[2]=94%; 95% PI: 5.9%, 90.4%). This also applied to single non-fibrotic changes, including ground glass opacity, consolidations, nodules/masses, parenchymal bands, and reticulations. The prevalence range of fibrotic traction bronchiectasis/bronchiolectasis was 1.6-25.7% (I[2]=93%; 95% PI: 0.0%, 98.6%;); honeycombing was unremarkable (0-1.1%; I[2]=58%; 95% PI: 0%, 60%). Lung sequelae were unrelated to any characteristics of interest. Conclusion The prevalence of COVID-19 lung sequelae at 1-year chest CT is highly heterogeneous among studies. Heterogeneity determinants remain unknown suggesting caution in data interpretation with no convincing evidence. PROSPERO (CRD42022341258) Keywords: COVID-19 pneumonia, pulmonary fibrosis, chest CT, long-COVID, systematic review, metaanalysis See also the editorial by Parraga and Svenningsen in this issue.}, } @article {pmid37402856, year = {2023}, author = {Hashimoto, K}, title = {Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis.}, journal = {Molecular psychiatry}, volume = {28}, number = {12}, pages = {4968-4976}, pmid = {37402856}, issn = {1476-5578}, support = {21H00184//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05612//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H02846//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Humans ; *Brain/virology ; *Brain-Gut Axis/physiology ; *COVID-19/complications ; Epstein-Barr Virus Infections/complications ; *Gastrointestinal Microbiome/physiology ; *Herpesvirus 4, Human/pathogenicity ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a serious public health burden worldwide. In addition to respiratory, heart, and gastrointestinal symptoms, patients infected with SARS-CoV-2 experience a number of persistent neurological and psychiatric symptoms, known as long COVID or "brain fog". Studies of autopsy samples from patients who died from COVID-19 detected SARS-CoV-2 in the brain. Furthermore, increasing evidence shows that Epstein-Barr virus (EBV) reactivation after SARS-CoV-2 infection might play a role in long COVID symptoms. Moreover, alterations in the microbiome after SARS-CoV-2 infection might contribute to acute and long COVID symptoms. In this article, the author reviews the detrimental effects of COVID-19 on the brain, and the biological mechanisms (e.g., EBV reactivation, and changes in the gut, nasal, oral, or lung microbiomes) underlying long COVID. In addition, the author discusses potential therapeutic approaches based on the gut-brain axis, including plant-based diet, probiotics and prebiotics, fecal microbiota transplantation, and vagus nerve stimulation, and sigma-1 receptor agonist fluvoxamine.}, } @article {pmid37402532, year = {2023}, author = {Waters, A}, title = {Long covid: nearly half of doctors affected can no longer work full time, finds survey.}, journal = {BMJ (Clinical research ed.)}, volume = {382}, number = {}, pages = {1529}, doi = {10.1136/bmj.p1529}, pmid = {37402532}, issn = {1756-1833}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Physicians ; Surveys and Questionnaires ; Employment ; }, } @article {pmid37400780, year = {2023}, author = {Overton, C and Emerson, T and A Evans, R and Armstrong, N}, title = {Responsive and resilient healthcare? 'Moments of Resilience' in post-hospitalisation services for COVID-19.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {720}, pmid = {37400780}, issn = {1472-6963}, support = {PCR-03-C19//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Aftercare ; Patient Discharge ; Delivery of Health Care ; Health Facilities ; }, abstract = {BACKGROUND: COVID-19 caused disruption to healthcare services globally, resulting in high numbers of hospital admissions and with those discharged often requiring ongoing support. Within the UK, post-discharge services typically developed organically and were shaped over time by local need, funding, and government guidance. Drawing on the Moments of Resilience framework, we explore the development of follow-up services for hospitalised patients by considering the links between resilience at different system levels over time. This study contributes to the resilient healthcare literature by providing empirical evidence of how diverse stakeholders developed and adapted services for patients following hospitalisation with COVID-19 and how action taken at one system level influenced another.

METHODS: Qualitative research comprising comparative case studies based on interviews. Across three purposively selected case studies (two in England, one in Wales) a total of 33 semi-structured interviews were conducted with clinical staff, managers and commissioners who had been involved in developing and/or implementing post-hospitalisation follow-up services. The interviews were audio-recorded and professionally transcribed. Analysis was conducted with the aid of NVivo 12.

RESULTS: Case studies demonstrated three distinct examples of how healthcare organisations developed and adapted their post-discharge care provision for patients, post-hospitalisation with COVID-19. Initially, the moral distress of witnessing the impact of COVID-19 on patients who were being discharged coupled with local demand gave clinical staff the impetus to take action. Clinical staff and managers worked closely to plan and deliver organisations' responses. Funding availability and other contextual factors influenced situated and immediate responses and structural adaptations to the post-hospitalisation services. As the pandemic evolved, NHS England and the Welsh government provided funding and guidance for systemic adaptations to post-COVID assessment clinics. Over time, adaptations made at the situated, structural, and systemic levels influenced the resilience and sustainability of services.

CONCLUSIONS: This paper addresses understudied, yet inherently important, aspects of resilience in healthcare by exploring when and where resilience occurs across the healthcare system and how action taken at one system level influenced another. Comparison across the case studies showed that organisations responded in similar and different ways and on varying timescales to a disruption and national level strategies.}, } @article {pmid37398785, year = {2023}, author = {Webb, Z}, title = {The Use of Bedside Echocardiography to Diagnose Post-COVID Cardiomyopathy and Left Ventricular Thrombus in the Emergency Department.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e39699}, pmid = {37398785}, issn = {2168-8184}, abstract = {This case report chronicles a 47-year-old male with no known past medical history, who presented to the emergency department with a chief complaint of progressive dyspnea and lower extremity edema. The patient was previously healthy until he contracted COVID-19 approximately six months prior to the date of presentation. He made a full recovery two weeks later. However, in the ensuing months, he progressively declined with worsening shortness of breath and lower extremity edema. On outpatient cardiology evaluation, he was found to have cardiomegaly on chest radiograph and sinus tachycardia on electrocardiogram. He was sent to the emergency department for further evaluation. In the emergency department, bedside echocardiography revealed dilated cardiomyopathy with left ventricular thrombus. Intravenous anticoagulation and diuresis were initiated, and the patient was subsequently admitted to the cardiac intensive care unit for further evaluation and management.}, } @article {pmid37398713, year = {2023}, author = {Weldon, EJ and Hong, B and Hayashi, J and Goo, C and Carrazana, E and Viereck, J and Liow, K}, title = {Mechanisms and Severity of Exercise Intolerance Following COVID-19 and Similar Viral Infections: A Comparative Review.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e39722}, pmid = {37398713}, issn = {2168-8184}, abstract = {Approximately 19% of the population is suffering from "Long COVID", also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), which often results in exercise intolerance. As COVID infections continue to be common, studying the long-term consequences of coronavirus disease (COVID) on physical function has become increasingly important. This narrative review will aim to summarize the current literature surrounding exercise intolerance following COVID infection in terms of mechanism, current management approaches, and comparison with similar conditions and will aim to define limitations in the current literature. Multiple organ systems have been implicated in the onset of long-lasting exercise intolerance post-COVID, including cardiac impairment, endothelial dysfunction, decreased VO2 max and oxygen extraction, deconditioning due to bed rest, and fatigue. Treatment modalities for severe COVID have also been shown to cause myopathy and/or worsen deconditioning. Besides COVID-specific pathophysiology, general febrile illness as commonly experienced during infection will cause hypermetabolic muscle catabolism, impaired cooling, and dehydration, which acutely cause exercise intolerance. The mechanisms of exercise intolerance seen with PASC also appear similar to post-infectious fatigue syndrome and infectious mononucleosis. However, the severity and duration of the exercise intolerance seen with PASC is greater than that of any of the isolated mechanisms described above and thus is likely a combination of the proposed mechanisms. Physicians should consider post-infectious fatigue syndrome (PIFS), especially if fatigue persists after six months following COVID recovery. It is important for physicians, patients, and social systems to anticipate exercise intolerance lasting for weeks to months in patients with long COVID. These findings underscore the importance of long-term management of patients with COVID and the need for ongoing research to identify effective treatments for exercise intolerance in this population. By recognizing and addressing exercise intolerance in patients with long COVID, clinicians can provide proper supportive interventions, such as exercise programs, physical therapy, and mental health counseling, to improve patient outcomes.}, } @article {pmid37398656, year = {2023}, author = {Bulla, R and Rossi, L and Furlanis, G and Agostinis, C and Toffoli, M and Balduit, A and Mangogna, A and Liccari, M and Morosini, G and Kishore, U and Manganotti, P}, title = {A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1191083}, pmid = {37398656}, issn = {1664-3224}, mesh = {Humans ; Brain ; *COVID-19/complications ; Lectins ; *Mannose-Binding Lectin/genetics ; *Post-Acute COVID-19 Syndrome/complications ; Quality of Life ; SARS-CoV-2 ; *Mental Fatigue/etiology ; }, abstract = {Brain fog can be described as a constellation of new-onset neuropsychiatric sequelae in the post-acute phase of COVID-19 (long COVID). The symptoms include inattention, short-term memory loss, and reduced mental acuity, which may undermine cognition, concentration, and sleep. This cognitive impairment, persisting for weeks or months after the acute phase of SARS-CoV-2 infection, can significantly impact on daily activities and the quality of life. An important role for the complement system (C) in the pathogenesis of COVID-19 has emerged since the beginning of pandemic outbreak. A number of pathophysiological characteristics including microangiopathy and myocarditis have been attributed to dysregulated C activation due to SARS-CoV-2 infection. Mannan-binding lectin (MBL), the first recognition subcomponent of the C lectin pathway, has been shown to bind to glycosylated SARS-CoV-2 spike protein, genetic variants of MBL2 are suggested to have an association with severe COVID-19 manifestations requiring hospitalization. In the present study, we evaluated MBL activity (lectin pathway activation) and levels in the sera of a cohort of COVID-19 patients, presenting brain fog or only hyposmia/hypogeusia as persistent symptoms, and compared them with healthy volunteers. We found significantly lower levels of MBL and lectin pathway activity in the sera of patients experiencing brain fog as compared to recovered COVID-19 patients without brain fog. Our data indicate that long COVID-associated brain fog can be listed among the variegate manifestations of increased susceptibility to infections and diseases contributed by MBL deficiency.}, } @article {pmid37398206, year = {2023}, author = {Acharya, A and Ambikan, AT and Thurman, M and Malik, MR and Dyavar, SR and Végvári, Á and Neogi, U and Byrareddy, SN}, title = {Proteomic landscape of astrocytes and pericytes infected with HIV/SARS-CoV-2 mono/co-infection, impacting on neurological complications.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37398206}, issn = {2693-5015}, support = {R01 DA052845/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: Although most individuals recover from coronavirus disease 2019 (COVID-19) within a few weeks, some people continue to experience a wide range of symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. Majority of patients with PASC develop neurological disorders like brain fog, fatigue, mood swings, sleep disorders, loss of smell and test among others collectively called neuro-PASC. While the people living with HIV (PWH) do not have a higher risk of developing severe disease and mortality/morbidity due to COVID-19. As a large section of PWH suffered from HIV-associated neurocognitive disorders (HAND), it is essential to understand the impact of neuro-PASC on people with HAND. In pursuit of this, we infected HIV/SARS-CoV-2 alone or together in primary human astrocytes and pericytes and performed proteomics to understand the impact of co-infection in the central nervous system.

METHODS: Primary human astrocytes and pericytes were infected with SARS-CoV-2 or HIV or HIV + SARS-CoV-2. The concentration of HIV and SARS-CoV-2 genomic RNA in the culture supernatant was quantified using reverse transcriptase quantitative real time polymerase chain reaction (RT-qPCR). This was followed by a quantitative proteomics analysis of mock, HIV, SARS-CoV-2, and HIV + SARS-CoV-2 infected astrocytes and pericytes to understand the impact of the virus in CNS cell types.

RESULTS: Both healthy and HIV-infected astrocytes and pericytes support abortive/low level of SARS-CoV-2 replication. In both mono-infected and co-infected cells, we observe a modest increase in the expression of SARS-CoV-2 host cell entry factors (ACE2, TMPRSS2, NRP1, and TRIM28) and inflammatory mediators (IL-6, TNF-α, IL-1β and IL-18). Quantitative proteomic analysis has identified uniquely regulated pathways in mock vs SARS-CoV-2, mock vs HIV + SARS-CoV-2, and HIV vs HIV + SARS-CoV-2 infected astrocytes and pericytes. The gene set enrichment analysis revealed that the top ten enriched pathways are linked to several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.

CONCLUSIONS: Our study emphasizes the significance of long-term monitoring of patients co-infected with HIV and SARS-CoV-2 to detect and understand the development of neurological abnormalities. By unraveling the molecular mechanisms involved, we can identify potential targets for future therapeutic interventions.}, } @article {pmid37397825, year = {2022}, author = {Robinson, JL and Le Saux, N}, title = {Children and long-COVID: Do they go together?.}, journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada}, volume = {7}, number = {4}, pages = {300-306}, pmid = {37397825}, issn = {2371-0888}, } @article {pmid37397682, year = {2023}, author = {Çınar, C and Kocakaya, D and Olgun Yıldızeli, S and Karakurt, S}, title = {Lung Cavitation as a Long-Term Imaging Pattern of COVID-19.}, journal = {Cureus}, volume = {15}, number = {6}, pages = {e39825}, pmid = {37397682}, issn = {2168-8184}, abstract = {Background A wide variety of radiological imaging findings, especially CT findings, have been reported in patients with COVID-19 pneumonia during the pandemic surge. Generally, on control chest imaging, individuals who have been cured of the disease usually show complete remission; however, in severe cases, residual pulmonary fibrosis, other abnormalities, and, rarely, lung cavitation can be observed. In this retrospective descriptive study, we aimed to describe the clinical, radiological, and laboratory characteristics of patients who developed lung cavitation in the course of SARS-CoV-2 disease recovery. Methodology Over a period of five months from March 1, 2021, to August 1, 2021, 15 consecutive patients who developed cavitary lesions on chest CT during the course of recovery from COVID-19 were recruited as the study population. All patients had a history of a SARS-CoV-2 infection diagnosed with a positive real-time polymerase chain reaction test. Patients who already had cavitary lesions in chest CT during the start of COVID-19 symptoms were excluded. Results In this study, 14 patients were male (93.3%). The only female patient was the only severely obese patient in the study population, with a body mass index was 40.4 kg/m[2]. The median (range) age of the patient population was 61 (42-79) years. Eight patients (53.3%) required intensive care unit admission during the hospitalization period. Three patients who required intensive care unit were intubated and needed invasive mechanical ventilation. Two patients died during hospitalization. Conclusions Lung cavitation remains a rare occurrence in the course of COVID-19. Bronchoscopic evaluation and scanning for pulmonary embolism should be done in appropriate patients to determine secondary reasons for cavitation. Although this descriptive study showed that cavitary lesions can develop in patients with severe disease, more comprehensive studies with a control group are needed to reach a definitive conclusion.}, } @article {pmid37396704, year = {2023}, author = {Del Carpio-Orantes, L}, title = {Etiopathogenic theories about long COVID.}, journal = {World journal of virology}, volume = {12}, number = {3}, pages = {204-208}, pmid = {37396704}, issn = {2220-3249}, abstract = {The main etiopathogenic theories of long coronavirus disease (COVID) are listed and a conjunction of them is carried out with the objective of deciphering the pathophysiology of the entity, finally the main lines of treatment existing in real life are discussed (Paxlovid, use of antibiotics in dysbiosis, triple anticoagulant therapy, temelimab).}, } @article {pmid37396577, year = {2023}, author = {Subramaniam, S and Reinhardt, C and Kulkarni, PP and Spiezia, L}, title = {Editorial: COVID-19 and thrombo-inflammatory responses.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1231909}, pmid = {37396577}, issn = {2297-055X}, } @article {pmid37394474, year = {2023}, author = {Sunada, N and Otsuka, Y and Honda, H and Tokumasu, K and Otsuka, F}, title = {Phase-dependent trends of male hypogonadism in long COVID patients.}, journal = {Endocrine journal}, volume = {70}, number = {7}, pages = {755-756}, doi = {10.1507/endocrj.EJ23-0266}, pmid = {37394474}, issn = {1348-4540}, mesh = {Humans ; Male ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Testosterone ; *Hypogonadism/complications/epidemiology ; }, } @article {pmid37394273, year = {2023}, author = {Wang, EJ and Dolomisiewicz, E and Karri, J and Tontisirin, N and Cohen, SP}, title = {Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.}, journal = {The Korean journal of pain}, volume = {36}, number = {3}, pages = {299-315}, pmid = {37394273}, issn = {2005-9159}, abstract = {The discovery and development of antimicrobial therapies represents one of the most significant advancements in modern medicine. Although the primary therapeutic intent of antimicrobials is to eliminate their target pathogens, several antimicrobials have been shown to provide analgesia as a secondary benefit. Antimicrobials have demonstrated analgesic effects in conditions that involve dysbiosis or potential subclinical infection (e.g ., chronic low back pain with Modic type 1 changes; chronic prostatitis/chronic pelvic pain; irritable bowel syndrome; inflammatory bowel disease; functional gastrointestinal disorders/dyspepsia; myalgic encephalomyelitis/chronic fatigue syndrome), and might even prevent the chronification of pain after acute infections that are associated with excessive systemic inflammation (e.g ., post COVID-19 condition/long Covid, rheumatic fever). Clinical studies often assess the analgesic effects of antimicrobial therapies in an observational manner, without the ability to identify causative relationships, and significant gaps in the understanding remain regarding the analgesic potential of antimicrobials. Numerous interrelated patient-specific, antimicrobial-specific, and disease-specific factors altogether contribute to the perception and experience of pain, and each of these requires further study. Given worldwide concerns regarding antimicrobial resistance, antimicrobials must continue to be used judiciously and are unlikely to be repurposed as primary analgesic medications. However, when equipoise exists among several antimicrobial treatment options, the potential analgesic benefits of certain antimicrobial agents might be a valuable aspect to consider in clinical decision-making. This article (the second in a two-part series) aims to comprehensively review the evidence on the prevention and treatment of chronic pain using antimicrobial therapies and suggest a framework for future studies on this topic.}, } @article {pmid37392341, year = {2023}, author = {Li, M and Wu, X and Shi, J and Niu, Y}, title = {Endothelium dysfunction and thrombosis in COVID-19 with type 2 diabetes.}, journal = {Endocrine}, volume = {82}, number = {1}, pages = {15-27}, pmid = {37392341}, issn = {1559-0100}, support = {81970924//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Anticoagulants/therapeutic use ; Post-Acute COVID-19 Syndrome ; Endothelial Cells ; *Diabetes Mellitus, Type 2/complications/drug therapy ; Quality of Life ; *Venous Thromboembolism/complications/drug therapy/prevention & control ; *Thrombosis/epidemiology/etiology/drug therapy ; Endothelium ; }, abstract = {SARS-CoV-2 can directly or indirectly damage endothelial cells. Endothelial injury, especially phosphatidylserine (PS) exposure on the outer membrane of cells, can more easily promote thrombosis. Type 2 diabetes(T2D) patients were more susceptible to COVID-19, they had more severe symptoms, higher risk of thrombotic complications, and longer duration of post-COVID-19 sequelae. This review provided a detailed overview of the mechanisms underlying endothelial dysfunction in T2D patients with COVID-19 (including long COVID), which may be influenced by hyperglycemia, hypoxia, and pro-inflammatory environments. The mechanisms of thrombosis in T2D patients with COVID-19 are also explored, particularly the effects of increased numbers of PS-exposing particles, blood cells, and endothelial cells on hypercoagulability. Given the high risk of thrombosis in T2D patients with COVID-19, early antithrombotic therapy can both minimize the impact of the disease on patients and maximize the chances of improvement, thereby alleviating patient suffering. We provided detailed guidance on antithrombotic drugs and dosages for mild, moderate, and severe patients, emphasizing that the optimal timing of thromboprophylaxis is a critical factor in influencing prognosis. Considering the potential interactions between antidiabetic, anticoagulant, and antiviral drugs, we proposed practical and comprehensive management recommendations to supplement the incomplete efficacy of vaccines in the diabetic population, reduce the incidence of post-COVID-19 sequelae, and improve patient quality of life.}, } @article {pmid37392031, year = {2023}, author = {Parums, DV}, title = {Editorial: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). Updated Terminology for the Long-Term Effects of COVID-19.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {29}, number = {}, pages = {e941595}, pmid = {37392031}, issn = {1643-3750}, mesh = {United States ; Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Most studies on the long-term effects of SARS-CoV-2 infection have been retrospective, have lacked an uninfected comparison group, and have focussed on the prevalence of individual symptoms, resulting in different estimates of prevalence. Recognizing the range and complex interactions between the many long-term effects of COVID-19 is essential before effective prevention or management strategies can be investigated and implemented. Therefore, the term, long COVID, is too simplistic, and there are reasons to replace it with the term, post-acute sequelae of SARS-CoV-2 infection (PASC). The National Institutes of Health (NIH) have established the Researching COVID to Enhance Recovery (RECOVER) Consortium, a prospective longitudinal cohort initiative to learn about the long-term effects of COVID-19. Analysis of the RECOVER data identified 37 symptoms involving multiple systems at 6 months. This Editorial aims to present the range and complex interactions between the many long-term effects of COVID-19 that support the updated terminology of PASC.}, } @article {pmid37391994, year = {2024}, author = {Fang, C and Baz, SA and Sheard, L and Carpentieri, JD}, title = {'I am just a shadow of who I used to be'-Exploring existential loss of identity among people living with chronic conditions of Long COVID.}, journal = {Sociology of health & illness}, volume = {46}, number = {1}, pages = {59-77}, doi = {10.1111/1467-9566.13690}, pmid = {37391994}, issn = {1467-9566}, support = {MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MR/S037527/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Existentialism ; Chronic Disease ; Qualitative Research ; Pain ; }, abstract = {Identity loss and (re)construction forms a central debate in sociology of chronic illness. Living with chronic/persistent health conditions may raise questions about how disruptions can touch upon and further threaten the very roots of existence, by which people reflexively perceive a coherent and stable sense of 'being-in-the-world'. Whilst medical sociologists have shown interest in 'existential loss' in chronic illness, this question remains largely underexplored. Adopting a qualitative study on Long COVID (LC) as an example, this article illuminates existential identity loss as a deeply painful experience of losing body as a fundamental medium to retain continuity and consistency of one's narratively constructed identity. Interviews with 80 LC sufferers in the UK revealed that living with persistent and often uncertain symptoms and disruptions can cause the loss of biographical resources and resilience, making it difficult to reflexively understand their own being within the world. Their dynamic responses to LC also highlighted how sufferers' longing for a narratively coherent self can profoundly shape the ongoing construction of their identity in chronic health conditions. These insights into the complicated and often hard-to-express existential pain of identity loss can also nurture more holistic understandings of and support for LC and chronic illness more broadly.}, } @article {pmid37391888, year = {2023}, author = {Rasmussen, IE and Løk, M and Durrer, CG and Foged, F and Schelde, VG and Budde, JB and Rasmussen, RS and Høvighoff, EF and Rasmussen, V and Lyngbæk, M and Jønck, S and Krogh-Madsen, R and Lindegaard, B and Jørgensen, PG and Køber, L and Vejlstrup, N and Klarlund Pedersen, B and Ried-Larsen, M and Lund, MAV and Christensen, RH and Berg, RMG}, title = {Impact of high-intensity interval training on cardiac structure and function after COVID-19: an investigator-blinded randomized controlled trial.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {135}, number = {2}, pages = {421-435}, doi = {10.1152/japplphysiol.00078.2023}, pmid = {37391888}, issn = {1522-1601}, support = {MFE-176582//CIHR/Canada ; }, mesh = {Female ; Humans ; Quality of Life ; *High-Intensity Interval Training ; *COVID-19 ; Heart ; *Cardiorespiratory Fitness ; }, abstract = {A large proportion of patients suffer from a persistent reduction in cardiorespiratory fitness after recovery from COVID-19, of which the effects on the heart may potentially be reversed through the effect of high-intensity interval training (HIIT). In the present study, we hypothesized that HIIT would increase left ventricular mass (LVM) and improve functional status and health-related quality of life (HRQoL) in individuals previously hospitalized for COVID-19. In this investigator-blinded, randomized controlled trial, 12 wk of supervised HIIT (4 × 4 min, three times a week) was compared with standard care (control) in individuals recently discharged from hospital due to COVID-19. LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), whereas the pulmonary diffusing capacity (DLCOc, secondary outcome) was examined by the single-breath method. Functional status and HRQoL were assessed by Post-COVID-19 functional scale (PCFS) and King's brief interstitial lung disease (KBILD) questionnaire, respectively. A total of 28 participants were included (age 57 ± 10, 9 females; HIIT: 58 ± 11, 4 females; standard care: 57 ± 9, 5 females), LVM increased in the HIIT vs. standard care group with a between-group difference of 6.8 [mean, 95%CI: 0.8; 12.8] g; P = 0.029. There were no between-group differences in DLCOc or any other lung function metric, which gradually resolved in both groups. Descriptively, PCFS suggested fewer functional limitations in the HIIT group. KBILD improved similarly in the two groups. HIIT is an efficacious exercise intervention for increasing LVM in individuals previously hospitalized for COVID-19.NEW & NOTEWORTHY In this randomized clinical trial on individuals previously hospitalized for COVID-19, a 12 wk supervised high-intensity interval training (HIIT) scheme was found to increase left ventricular mass, whereas pulmonary diffusing capacity was unaffected. The findings indicate that HIIT is an efficacious exercise intervention for targeting the heart after COVID-19.}, } @article {pmid37391116, year = {2023}, author = {Seeley, MC and Gallagher, C and Ong, E and Langdon, A and Chieng, J and Bailey, D and Page, A and Lim, HS and Lau, DH}, title = {High Incidence of Autonomic Dysfunction and Postural Orthostatic Tachycardia Syndrome in Patients with Long COVID: Implications for Management and Health Care Planning.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, pmid = {37391116}, issn = {1555-7162}, abstract = {BACKGROUND: Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), has been reported in individuals with post-acute sequelae of COVID-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls.

METHODS: All participants were prospectively enrolled between August 5, 2021 and October 31, 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio, and orthostatic changes during a 10-minute active standing test, as well as sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the EuroQuol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures.

RESULTS: A total of 99 participants (n = 33 PASC, n = 33 POTS, and n = 33 healthy controls; median age 32 years, 85.9% females) were included. Compared with healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (P < .001), greater heart rate increase during 10-minute active standing test (P < .001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all P < .001), and poor HrQoL across all EQ-5D-5L domains (all P < .001), lower median EuroQol-visual analogue scale (P < .001), and lower utility scores (P < .001). The majority (79%) of those with PASC met the internationally established criteria for POTS.

CONCLUSION: The prevalence of autonomic symptomology for POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.}, } @article {pmid37390849, year = {2023}, author = {Rouen, A and Taïeb, J and Caetano, G and Pitron, V and Elbaz, M and Salmon, D and Leger, D}, title = {Polysomnographic parameters in long-COVID chronic insomnia patients.}, journal = {Dialogues in clinical neuroscience}, volume = {25}, number = {1}, pages = {43-49}, pmid = {37390849}, issn = {1958-5969}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders ; *COVID-19/complications ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: While COVID-19 is predominantly considered to be an acute self-remitting disease, it has been pointed out that a variety of symptoms can linger for several months, a phenomenon identified as long-COVID. Insomnia is particularly prevalent in long-COVID. In the present study, we aimed at confirming and characterising insomnia in long-COVID patients through polysomnography and to identify whether its parameters differ from patients with chronic insomnia and no long-COVID history.

MATERIALS AND METHODS: We conducted a case-control study, including 17 long-COVID patients with insomnia symptoms (cases), and 34 2:1 matched controls with a diagnostic of chronic insomnia and no history of long-COVID. All underwent a one-night polysomnography (PSG).

RESULTS: First, we observed that long-COVID patients with insomnia complaints have altered PSG parameters, in favour of the diagnosis of chronic insomnia. Second, we show that insomnia related to long-COVID PSG parameters was not significantly different from regular chronic insomnia PSG parameters.

DISCUSSION: Our results indicate that even though it is one of the most prevalent symptoms of long-COVID, its related insomnia resembles typical chronic insomnia, based on PSG studies. Even though additional studies are warranted, our results suggest that the pathophysiology and therapeutic options should be similar to those recommended for chronic insomnia.}, } @article {pmid37389526, year = {2023}, author = {Bilu, Y and Flaks-Manov, N and Goldshtein, I and Bivas-Benita, M and Akiva, P and Bodenheimer, G and Greenfeld, S}, title = {Youth Mental Health Outcomes up to Two Years After SARS-CoV-2 Infection Long-COVID or Long-Pandemic Syndrome: A Retrospective Cohort Study.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {73}, number = {4}, pages = {701-706}, doi = {10.1016/j.jadohealth.2023.05.022}, pmid = {37389526}, issn = {1879-1972}, mesh = {Adolescent ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; Outcome Assessment, Health Care ; }, abstract = {PURPOSE: Youth mental distress has substantially increased during the COVID-19 pandemic. However, it is unclear if mental symptoms are directly related to SARS-CoV-2 infection or to social restrictions. We aimed to investigate mental health outcomes in infected versus uninfected adolescents, for up to two years after an index polymerase chain reaction (PCR) test.

METHODS: A retrospective cohort study, based on electronic health records from a large nationally representative Israeli health fund, among adolescents aged 12-17 years with a PCR test for SARS-CoV-2 between March 1, 2020 and March 1, 2021. Infected and uninfected individuals were matched by age, sex, test date, sector, and socioeconomic status. Cox regression was used to derive hazard ratios (HRs) for mental health outcomes within two years from PCR test for infected versus uninfected individuals, while accounting for pre-existing psychiatric history. External validation was performed on UK primary care data.

RESULTS: Among 146,067 PCR-tested adolescents, 24,009 were positive and 22,354 were matched with negative adolescents. SARS-CoV-2 infection was significantly associated with reduced risks for dispensation of antidepressants (HR 0.74, 95% confidence interval [CI] 0.66-0.83), diagnoses of anxiety (HR 0.82, 95% CI 0.71-0.95), depression (HR 0.65, 95% CI 0.53-0.80), and stress (HR 0.80, 95% CI 0.69-0.92). Similar results were obtained in the validation dataset.

DISCUSSION: This large, population-based study suggests that SARS-CoV-2 infection is not associated with elevated risk for mental distress in adolescents. Our findings highlight the importance of taking a holistic view on adolescents' mental health during the pandemic, with consideration of both SARS-CoV-2 infection and response measures.}, } @article {pmid37389402, year = {2023}, author = {Lopes, LA and Agrawal, DK}, title = {Thromboembolism in the Complications of Long COVID-19.}, journal = {Cardiology and cardiovascular medicine}, volume = {7}, number = {2}, pages = {123-128}, pmid = {37389402}, issn = {2572-9292}, support = {R01 HL144125/HL/NHLBI NIH HHS/United States ; R01 HL147662/HL/NHLBI NIH HHS/United States ; }, abstract = {SARS-CoV-2 is a +ssRNA helical coronavirus responsible for the global pandemic caused by coronavirus disease 19 (COVID-19). Classical clinical symptoms from primary COVID-19 when symptomatic include cough, fever, pneumonia or even ARDS; however, they are limited primarily to the respiratory system. Long-COVID-19 sequalae is responsible for many pathologies in almost every organ system and may be present in up to 30% of patients who have developed COVID-19. Our review focuses on how long-COVID-19 (3 -24 weeks after primary symptoms) may lead to an increased risk for stroke and thromboembolism. Patients who were found to be primarily at risk for thrombotic events included critically ill and immunocompromised patients. Additional risk factors for thromboembolism and stroke included diabetes, hypertension, respiratory and cardiovascular disease, and obesity. The etiology of how long-COVID-19 leads to a hypercoagulable state are yet to be definitively elucidated. However, anti-phospholipid antibodies and elevated D-dimer are present in many patients who develop thromboembolism. In addition, chronic upregulation and exhaustion of the immune system may lead to a pro-inflammatory and hypercoagulable state, increasing the likelihood for induction of thromboembolism or stroke. This article provides an up-to-date review on the proposed etiologies for thromboembolism and stroke in patients with long-COVID-19 and to assist health care providers in examining patients who may be at a higher risk for developing these pathologies.}, } @article {pmid37389095, year = {2023}, author = {Sumantri, S and Rengganis, I}, title = {Immunological dysfunction and mast cell activation syndrome in long COVID.}, journal = {Asia Pacific allergy}, volume = {13}, number = {1}, pages = {50-53}, pmid = {37389095}, issn = {2233-8276}, abstract = {At least 65 million people around the world suffer from long COVID-19, with the majority of cases occurring in the productive age (36-50 years old). Individuals with long COVID-19 are confounded with multiple organ system dysfunctions, long-term organ injury sequelae, and a decreased quality of life. There is an overlapping of risk factors between long COVID-19 and other postviral infection syndromes, so advances in research could also benefit other groups of patients. Long COVID-19 is the consequence of multiple immune system dysregulation, such as T-cell depletion, innate immune cell hyperactivity, lack of naive T and B cells, and elevated signature of pro-inflammatory cytokines, together with persistent severe acute respiratory syndrome-coronavirus 2 reservoir and other consequences of acute infection. There is an activated condition of mast cells in long COVID-19, with abnormal granulation and excessive inflammatory cytokine release. A study by Weinstock et al. indicates that patients with long COVID-19 suffer the same clinical syndrome as patients with mast cell activation syndrome (MCAS). Diagnosis and treatment of MCAS in patients with long COVID-19 will provide further symptomatic relief, and manage mast cell-mediated hyperinflammation states, which could be useful in the long-term control and recovery of such patients.}, } @article {pmid37388814, year = {2023}, author = {Marshall, GD}, title = {The pathophysiology of postacute sequelae of COVID-19 (PASC): Possible role for persistent inflammation.}, journal = {Asia Pacific allergy}, volume = {13}, number = {2}, pages = {77-84}, pmid = {37388814}, issn = {2233-8276}, support = {U54 GM115428/GM/NIGMS NIH HHS/United States ; }, abstract = {UNLABELLED: As the SARS-CoV-2-induced pandemic wanes, a substantial number of patients with acute Corona Virus-induced disease (COVID-19 continue to have symptoms for a prolonged time after initial infection. These patients are said to have postacute sequelae of COVID (PASC) or "long COVID". The underlying pathophysiology of this syndrome is poorly understood and likely quite heterogeneous. The role of persistent, possibly deviant inflammation as a major factor in comorbidity is suspected.

OBJECTIVE: To review data that address the relative importance of inflammation in the pathophysiology spectrum of PASC and to address how this would impact diagnosis and approach to therapy in patients identified as having such inflammatory abnormalities.

METHODS: A review of public databases, including PubMed, MeSH, NLM catalog, and clinical trial databases such as clinicaltrials.gov.

RESULTS: The literature supports a prominent role for various forms and types of inflammation in the pathophysiologic spectrum of PASC. Such inflammation can be persistent ant CoV-2-specific responses, new onset autoimmune responses, or a loss of normal immunoregulation resulting in widespread, sustained inflammatory pathologies that can affect both broad constitutional symptoms (such as fatigue, neurocognitive dysfunction, and anxiety/depression) and organ-specific dysfunction and/or failure.

CONCLUSIONS: PASC is a significant clinical entity with similarities to and differences from other postviral syndromes. Significant research efforts are ongoing to better understand specific aberrant inflammatory pathways present in individual patients for the purpose of developing and implementing effective therapies and ultimately prophylaxis strategies to prevent the progression of COVID-19 as well as likely future viral illnesses and pandemics.}, } @article {pmid37388279, year = {2023}, author = {Zadeh, FH and Wilson, DR and Agrawal, DK}, title = {Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies.}, journal = {Archives of microbiology & immunology}, volume = {7}, number = {2}, pages = {36-61}, pmid = {37388279}, issn = {2572-9365}, support = {R01 HL144125/HL/NHLBI NIH HHS/United States ; R01 HL147662/HL/NHLBI NIH HHS/United States ; }, abstract = {Long Covid is one of the most prevalent and puzzling conditions that arose with the Covid pandemic. Covid-19 infection generally resolves within several weeks but some experience new or lingering symptoms. Though there is no formal definition for such lingering symptoms the CDC boadly describes long Covid as persons having a wide range of new, recurring or sustained health issues four or more weeks after first being infected with SARS-CoV2. The WHO defines long Covid as the manifestation of symptoms from a "probable or confirmed" Covid-19 infection that start approximately 3 months after the onset of the acute infection and last for more than 2 months. Numerous studies have looked at the implications of long Covid on various organs. Many specific mechanisms have been proposed for such changes. In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies. We also review various treatment options, current clinical trials, and other potential therapeutic avenues to control long Covid followed by the information about the effect of vaccination on long Covid. Lastly, we discuss some of the questions and knowledge gaps in the present understanding of long Covid. We believe more studies of the effects long Covid has on quality of life, future health and life expectancy are required to better understand and eventually prevent or treat the disease. We acknowledge the effects of long Covid are not limited to those in this article but as it may affect the health of future offspring and therefore, we deem it important to identify more prognostic and therapeutic targets to control this condition.}, } @article {pmid37387323, year = {2024}, author = {Kandemir, H and Bülbül, GA and Kirtiş, E and Güney, S and Sanhal, CY and Mendilcioğlu, İİ}, title = {Evaluation of long-COVID symptoms in women infected with SARS-CoV-2 during pregnancy.}, journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics}, volume = {164}, number = {1}, pages = {148-156}, doi = {10.1002/ijgo.14972}, pmid = {37387323}, issn = {1879-3479}, mesh = {Humans ; Female ; Pregnancy ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Myalgia ; Retrospective Studies ; Cross-Sectional Studies ; Arthralgia ; }, abstract = {OBJECTIVE: To evaluate the symptoms of Long COVID (LC), frequency of symptoms, and possible risk factors in women diagnosed with coronavirus disease 2019 (COVID-19) during pregnancy.

METHODS: We conducted a single-center, cross-sectional, retrospective study in 99 pregnant women who were polymerase chain reaction-positive (PCR+) for COVID-19 between March 1, 2020 and April 30, 2022. The control group consisted of 99 women who gave birth between these dates and did not have COVID-19. We evaluated the clinical manifestations, symptom prevalence, and symptom characteristics of acute COVID-19 and the LC in the PCR+ group as well as questioned the control group for LC symptoms.

RESULTS: Of the women in the PCR+ group, 74 (74.7%) had at least one LC symptom, and the most common symptoms were fatigue (54; 72.9%), myalgia/arthralgia (49; 66.2%), and anosmia/ageusia (31; 41.9%). The rate of LC symptoms in the control group was 14 (14.1%). The prevalence of LC symptoms was higher in severely/critically symptomatic patients (23; 100%) in the acute period of disease than in asymptomatic/mildly symptomatic (51; 67.1%) (P = 0.005). Hospitalization during acute infection (adjusted odds ratio [aOR] = 13.30), having one or more symptoms (aOR = 4.75), and having symptoms such as cough (aOR = 6.27) and myalgia/arthralgia (aOR = 12.93) increased the likelihood of LC.

CONCLUSION: Many women experienced LC after suffering acute COVID-19 in pregnancy, but LC prevalence was similar to the general population. LC correlates with severity, type, and number of symptoms of acute COVID-19.}, } @article {pmid37387088, year = {2023}, author = {Katika, A and Zoulias, E and Koufi, V and Malamateniou, F}, title = {Mining Greek Tweets on Long COVID Using Sentiment Analysis and Topic Modeling.}, journal = {Studies in health technology and informatics}, volume = {305}, number = {}, pages = {545-548}, doi = {10.3233/SHTI230554}, pmid = {37387088}, issn = {1879-8365}, mesh = {Child ; Humans ; *Post-Acute COVID-19 Syndrome ; Sentiment Analysis ; *COVID-19 ; COVID-19 Vaccines ; Greece ; }, abstract = {Around 10% to 20% of patients experience Long COVID after recovering from COVID-19. Many people are turning to social networks such as Facebook, WhatsApp, Twitter, etc., to express their opinions and feelings regarding Long COVID. In this paper, we analyse text messages in the Greek language posted on the Twitter platform in 2022 to extract popular discussion topics and classify the sentiment of Greek citizens regarding Long COVID. Results highlighted the following discussion topics: Greek-speaking users discuss Long COVID effects and time required to heal, Long COVID effects in specific population groups like children and COVID-19 vaccines. 59% of analysed tweets conveyed a negative sentiment while the rest had positive or neutral sentiment. The analysis shows that public bodies could benefit from systematically mining knowledge from social media to understand public's perception of a new disease and take action.}, } @article {pmid37386857, year = {2024}, author = {Składanek, JA and Leśkiewicz, M and Gumiężna, K and Baruś, P and Piasecki, A and Klimczak-Tomaniak, D and Sygitowicz, G and Kochman, J and Grabowski, M and Tomaniak, M}, title = {Long COVID and its cardiovascular consequences: What is known?.}, journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University}, volume = {33}, number = {3}, pages = {299-308}, doi = {10.17219/acem/167482}, pmid = {37386857}, issn = {1899-5276}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cardiovascular System ; Arrhythmias, Cardiac ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.}, } @article {pmid37386538, year = {2022}, author = {Cortegiani, A and Tripodi, VF and Castioni, CA and Esposito, C and Galdieri, N and Monzani, R and Rispoli, M and Simonini, A and Torrano, V and Giarratano, A and Gratarola, A}, title = {Timing of surgery and elective perioperative management of patients with previous SARS-CoV-2 infection: a SIAARTI expert consensus statement.}, journal = {Journal of anesthesia, analgesia and critical care}, volume = {2}, number = {1}, pages = {29}, pmid = {37386538}, issn = {2731-3786}, abstract = {BACKGROUND: The appropriate timing of surgery and perioperative management of patients with previous SARS-CoV-2 infection are open issues. The purpose of this document is to support the clinical decision-making process regarding the patient with previous Sars-CoV-2 infection to undergo elective surgery. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient's surgical process.

METHODS: The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) selected 11 experts to reach a consensus on key aspects of this theme in adult and pediatric population. The methods of this process document were in accordance to the principles of rapid review of the scientific literature and modified Delphi method. The experts produced statements and supporting reasons in the form of an informative text. The overall list of statements was subjected to a vote in order to express the degree of consent.

RESULTS: Patients should not undergo elective surgery within 7 weeks of infection unless there is the risk of a negative evolution of the disease. To mitigate the risk of postsurgical mortality, a multidisciplinary approach seemed useful in addition to the use of validated algorithms to estimate the risk of perioperative morbidity and mortality; the risk related to SARS-CoV-2 infection should be added. The risk of potential nosocomial contagion from a positive patients should also be considered when deciding to proceed with surgery. Most of the evidence came from previous SARS-CoV-2 variants, so the evidence should be considered indirect.

CONCLUSION: A balanced preoperative multidisciplinary risk-benefit evaluation is needed in patients with previous infection by SARS-CoV-2 for elective surgery.}, } @article {pmid37386178, year = {2023}, author = {Graham, F}, title = {Daily briefing: Answers emerge about long COVID recovery.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-023-02190-8}, pmid = {37386178}, issn = {1476-4687}, } @article {pmid37385286, year = {2023}, author = {Buonsenso, D and Martino, L and Morello, R and Mariani, F and Fearnley, K and Valentini, P}, title = {Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies.}, journal = {The Lancet. Microbe}, volume = {4}, number = {9}, pages = {e745-e756}, pmid = {37385286}, issn = {2666-5247}, mesh = {Adult ; Systemic Inflammatory Response Syndrome ; Child ; Research Design ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *SARS-CoV-2/genetics ; RNA, Viral ; }, abstract = {In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions. Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.}, } @article {pmid37383150, year = {2023}, author = {Suputtitada, A}, title = {Editorial: Highlights in medical and surgical rehabilitation 2021/22.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1219924}, pmid = {37383150}, issn = {2673-6861}, } @article {pmid37382292, year = {2023}, author = {Huijts, T and Gage Witvliet, M and Balaj, M and Andreas Eikemo, T}, title = {Assessing the long-term health impact of COVID-19: The importance of using self-reported health measures.}, journal = {Scandinavian journal of public health}, volume = {51}, number = {5}, pages = {645-647}, pmid = {37382292}, issn = {1651-1905}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Self Report ; Pandemics ; *Population Health ; }, abstract = {It is estimated that at least one out of 10 people who contracted COVID-19 continue to experience health problems long after the clearance of the acute infection. These belong to the growing group of people who have post-acute sequelae of SARS CoV-2 infection or long COVID, a multifaceted condition involving multiple organ systems. Given the lack of clear definition and diagnosis, this marked increase in the number of people who have long COVID might not be fully reflected in data on population health in the years to come. In this editorial, we argue that the use of self-reported health measures is vital for fully assessing the long-term impact of the COVID-19 pandemic on health and health inequalities. After briefly introducing self-reported health measures, we discuss strengths and limitations of specific measures that capture direct self-reports of long COVID. We then outline how the impact of long COVID may also be reflected in response patterns to more general self-reported health measures and give suggestions on how these can be used to examine the long-term health impact of the COVID-19 pandemic.}, } @article {pmid37380640, year = {2023}, author = {Ding, Q and Zhao, H}, title = {Long-term effects of SARS-CoV-2 infection on human brain and memory.}, journal = {Cell death discovery}, volume = {9}, number = {1}, pages = {196}, pmid = {37380640}, issn = {2058-7716}, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with the high transmissibility and increased immune escape against vaccines. Because of the multiple basic amino acids in the S1-S2 junction of spike protein, the widespread distribution of angiotensin-converting enzyme 2 (ACE2) receptor in human body and the high transmissibility, SARS-CoV-2 can infect multiple organs and has led to over 0.7 billion infectious cases. Studies showed that SARS-CoV-2 infection can cause more than 10% patients with the Long-COVID syndrome, including pathological changes in brains. This review mainly provides the molecular foundations for understanding the mechanism of SARS-CoV-2 invading human brain and the molecular basis of SARS-CoV-2 infection interfering with human brain and memory, which are associated with the immune dysfunction, syncytia-induced cell death, the persistence of SARS-CoV-2 infection, microclots and biopsychosocial aspects. We also discuss the strategies for reducing the Long-COVID syndrome. Further studies and analysis of shared researches will allow for further clarity regarding the long-term health consequences.}, } @article {pmid37380223, year = {2023}, author = {Seo, Y and Le, T and Georgoudiou, S and Austin, R and Jantraporn, R and Monsen, KA}, title = {Synthesis of Long COVID Symptoms: An Evidence-Based Standardized Mapping Study With the Omaha System.}, journal = {Research and theory for nursing practice}, volume = {}, number = {}, pages = {}, doi = {10.1891/RTNP-2022-0146}, pmid = {37380223}, issn = {1541-6577}, abstract = {Background: In COVID-19 survivors, symptom burden is a significant and multifaceted personal and societal challenge. The Omaha system is a standardized terminology used by researchers and clinicians for documentation and analysis of meaningful data for whole-person health. Given the urgent need for a standardized symptom checklist specific to the long COVID population, the purpose of the present study was to identify long COVID symptoms from the published literature (native symptoms) and map those to the Omaha system signs/symptoms terms. Methods: The long COVID symptoms identified from 13 literatures were mapped to the Omaha system signs/symptoms, using an expert consensus approach. The criteria for mapping were that the long COVID signs/symptoms had to contain either a one-to-one match (exact meaning of the native terms and the signs/symptoms) or a partial match (similar but not exact meaning). Results: The synthesis of the 217 native symptoms of long COVID and mapping analysis to the Omaha problems and signs/symptoms level resulted in a combined, deduplicated, and standardized list of 74 signs/symptoms for 23 problems. Of these, 72 (97.3%) of native signs/symptoms were a full match at the problem level, and 67 (90.5%) of native signs/symptoms were a full or partial match at the sign/symptoms level. Conclusions: The present study is the first step in identifying a standardized evidence-based symptom checklist for long COVID patients. This checklist may be used in practice and research for assessment, tracking, and intervention planning as well as longitudinal analysis of symptom resolution and intervention effectiveness.}, } @article {pmid37379850, year = {2023}, author = {Kim, J and Young, GS}, title = {Neuroimaging of COVID-19.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {205-218}, doi = {10.1055/s-0043-1767771}, pmid = {37379850}, issn = {1098-9021}, mesh = {Humans ; *COVID-19/complications ; *Posterior Leukoencephalopathy Syndrome ; Post-Acute COVID-19 Syndrome ; *Guillain-Barre Syndrome ; Inflammation ; }, abstract = {We review the wide variety of common neuroimaging manifestations related to coronavirus disease 2019 (COVID-19) and COVID therapies, grouping the entities by likely pathophysiology, recognizing that the etiology of many entities remains uncertain. Direct viral invasion likely contributes to olfactory bulb abnormalities. COVID meningoencephalitis may represent direct viral infection and/or autoimmune inflammation. Para-infectious inflammation and inflammatory demyelination at the time of infection are likely primary contributors to acute necrotizing encephalopathy, cytotoxic lesion of the corpus callosum, and diffuse white matter abnormality. Later postinfectious inflammation and demyelination may manifest as acute demyelinating encephalomyelitis, Guillain-Barré syndrome, or transverse myelitis. The hallmark vascular inflammation and coagulopathy of COVID-19 may produce acute ischemic infarction, microinfarction contributing to white matter abnormality, space-occupying hemorrhage or microhemorrhage, venous thrombosis, and posterior reversible encephalopathy syndrome. Adverse effects of therapies including zinc, chloroquine/hydroxychloroquine, antivirals, and vaccines, and current evidence regarding "long COVID" is briefly reviewed. Finally, we present a case of bacterial and fungal superinfection related to immune dysregulation from COVID.}, } @article {pmid37378781, year = {2023}, author = {Taner, N and Haskologlu, IC and Erdag, E and Mercan, M and Chuckwunyere, U and Ulker, D and Sehirli, AO and Abacioglu, N}, title = {Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.}, journal = {Advances in experimental medicine and biology}, volume = {1412}, number = {}, pages = {427-442}, pmid = {37378781}, issn = {0065-2598}, mesh = {Humans ; Phytotherapy ; Plant Extracts/therapeutic use ; *Pelargonium ; *Melatonin/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; Plant Roots ; }, abstract = {Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.}, } @article {pmid37378769, year = {2023}, author = {Turton, N and Millichap, L and Hargreaves, IP}, title = {Potential Biomarkers of Mitochondrial Dysfunction Associated with COVID-19 Infection.}, journal = {Advances in experimental medicine and biology}, volume = {1412}, number = {}, pages = {211-224}, pmid = {37378769}, issn = {0065-2598}, mesh = {Humans ; *Mitochondrial Diseases/diagnosis/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Mitochondria/metabolism ; Biomarkers ; }, abstract = {Mitochondria play crucial roles in modulating immune responses, and viruses can in turn moderate mitochondrial functioning. Therefore, it is not judicious to assume that clinical outcome experienced in patients with COVID-19 or long COVID may be influenced by mitochondrial dysfunction in this infection. Also, patients who are predisposed to mitochondrial respiratory chain (MRC) disorders may be more susceptible to worsened clinical outcome associated with COVID-19 infection and long COVID. MRC disorders and dysfunction require a multidisciplinary approach for their diagnosis of which blood and urinary metabolite analysis may be utilized, including the measurement of lactate, organic acid and amino acid levels. More recently, hormone-like cytokines including fibroblast growth factor-21 (FGF-21) have also been used to assess possible evidence of MRC dysfunction. In view of their association with MRC dysfunction, assessing evidence of oxidative stress parameters including GSH and coenzyme Q10 (CoQ10) status may also provide useful biomarkers for diagnosis of MRC dysfunction. To date, the most reliable biomarker available for assessing MRC dysfunction is the spectrophotometric determination of MRC enzyme activities in skeletal muscle or tissue from the disease-presenting organ. Moreover, the combined use of these biomarkers in a multiplexed targeted metabolic profiling strategy may further improve the diagnostic yield of the individual tests for assessing evidence of mitochondrial dysfunction in patients pre- and post-COVID-19 infection.}, } @article {pmid37378376, year = {2023}, author = {Tayar, E and Isber, R and Isber, N}, title = {Long COVID treated successfully with antivirals in a rituximab-treated follicular lymphoma patient with persistent negative-antibodies to SARS-CoV2.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e17149}, pmid = {37378376}, issn = {2405-8440}, abstract = {Long COVID is a well-known complication to COVID-19 that affect millions of people worldwide and causes wide range of symptoms. We present a rare case of a previously diagnosed follicular lymphoma patient, who had a long COVID with persistent negative SARS-CoV-2 antibodies and required an aggressive antiviral treatment.}, } @article {pmid37378093, year = {2023}, author = {Sayegh, MN and Goins, AE and Hall, MAK and Shin, YM}, title = {Presentations, Diagnosis, and Treatment of Post-COVID Viral Myocarditis in the Inpatient Setting: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {5}, pages = {e39338}, pmid = {37378093}, issn = {2168-8184}, abstract = {While coronavirus disease 2019 (COVID-19) infection rates have declined, and mortality outcomes have improved with vaccines, targeted antiviral therapies, and improved care practices over the course of the pandemic, post-acute sequelae of SARS CoV-2 infection (PASC, also referred to as "long COVID") has emerged as a significant concern, even among individuals who appear to have fully recovered from their initial infection. Acute COVID-19 infection is associated with myocarditis and cardiomyopathies, but the prevalence and presentation of post-infectious myocarditis are unclear. We provide a narrative review of post-COVID myocarditis, including symptoms and signs, physical exam findings, diagnosis, and treatment strategies. Post-COVID myocarditis has a wide range of presentations, from very mild symptoms to severe ones that can include sudden cardiac death. Several studies have noted what appears to be a bimodal distribution of affected patients, with individuals under age 16 (particularly males) most affected, followed by those over age 50. The gold standard of diagnosis for myocarditis is endomyocardial biopsy and cardiac magnetic resonance imaging with a confirmed diagnosis of COVID-19. However, if these are not available, other studies such as electrocardiogram, echocardiography, and inflammatory markers can guide clinicians to diagnose post-COVID myocarditis when appropriate. Treatment is largely supportive and may include oxygen therapy, intravenous hydration, diuretics, steroids, and antivirals. Post-COVID myocarditis is rare but important to recognize as more patients present with this condition in the inpatient setting.}, } @article {pmid37376668, year = {2023}, author = {Babicki, M and Kapusta, J and Pieniawska-Śmiech, K and Kałuzińska-Kołat, Ż and Kołat, D and Mastalerz-Migas, A and Jankowski, P and Chudzik, M}, title = {Do COVID-19 Vaccinations Affect the Most Common Post-COVID Symptoms? Initial Data from the STOP-COVID Register-12-Month Follow-Up.}, journal = {Viruses}, volume = {15}, number = {6}, pages = {}, pmid = {37376668}, issn = {1999-4915}, mesh = {Humans ; *COVID-19 Vaccines ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Vaccination ; Headache ; }, abstract = {Around the world, various vaccines have been developed to prevent the SARS-CoV-2 virus infection and consequently the COVID-19 disease. However, many patients continue to report persistent symptoms after the acute phase. Since gathering scientific information on long COVID and post-COVID syndrome has become an urgent issue, we decided to investigate them in relation to the vaccination status of patients from the STOP-COVID registry. In this retrospective study, we analyzed data from the medical visit after contraction of COVID-19 and follow-up visits in the 3rd and 12th month after the disease. In total, 801 patients were included in the analysis. The most frequent complaints after 12 months included deterioration of exercise tolerance (37.5%), fatigue (36.3%), and memory/concentration difficulties (36.3%). In total, 119 patients declared that they had been diagnosed with at least one new chronic disease since the end of isolation, and 10.6% required hospitalization. The analysis of individual symptoms revealed that headache (p = 0.001), arthralgia (p = 0.032), and dysregulation of hypertension (p = 0.030) were more common in unvaccinated patients. Considering headache and muscle pain, people vaccinated after the disease manifested these symptoms less frequently. Subsequent research is needed to consider vaccines as a preventive factor for post-COVID syndrome.}, } @article {pmid37376625, year = {2023}, author = {Kirchberger, I and Meisinger, C and Warm, TD and Hyhlik-Dürr, A and Linseisen, J and Goßlau, Y}, title = {Post-COVID-19 Syndrome in Non-Hospitalized Individuals: Healthcare Situation 2 Years after SARS-CoV-2 Infection.}, journal = {Viruses}, volume = {15}, number = {6}, pages = {}, pmid = {37376625}, issn = {1999-4915}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Hospitals, University ; Polymerase Chain Reaction ; Patient Acceptance of Health Care ; }, abstract = {Although "post-COVID-19 syndrome" (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection. Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers. The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers.}, } @article {pmid37375809, year = {2023}, author = {Chittasupho, C and Srisawad, K and Arjsri, P and Phongpradist, R and Tingya, W and Ampasavate, C and Dejkriengkraikul, P}, title = {Targeting Spike Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {6}, pages = {}, pmid = {37375809}, issn = {1424-8247}, support = {FRB660046/0162_FF66/020//Fundamental Fund, Chiang Mai University and Thailand Science Research and Innovation, Thailand/ ; }, abstract = {Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin was prepared by encapsulating curcumin extract in phospholipids. The particle size, polydispersity index, and zeta potential of nanocurcumin were measured using dynamic light scattering. The encapsulated curcumin content was determined using HPLC analysis. The encapsulation efficiency of curcumin was 90.74 ± 5.35% as determined by HPLC. Regarding the in vitro release of curcumin, nanocurcumin displayed a higher release content than non-nanoparticle curcumin. Nanocurcumin was further investigated for its anti-inflammatory properties using A549 lung epithelial cell line. As determined by ELISA, nanocurcumin showed inhibitory effects on inflammatory cytokine releases in CoV2-SP-stimulated conditions, as evidenced by a significant decrease in IL-6, IL-1β and IL-18 cytokine secretions compared with the spike-stimulated control group (p < 0.05). Additionally, as determined by RT-PCR, nanocurcumin significantly inhibited the CoV2-SP-stimulated expression of inflammatory genes (IL-6, IL-1β, IL-18, and NLRP3) compared with the spike-stimulated control group (p < 0.05). Regarding the inhibition of NLRP3 inflammasome machinery proteins by Western blot, nanocurcumin decreased the expressions of inflammasome machinery proteins including NLRP3, ASC, pro-caspase-1, and the active form of caspase-1 in CoV2-SP-stimulated A549 cells compared with the spike-stimulated control group (p < 0.05). Overall, the nanoparticle formulation of curcumin improved its solubility and bioavailability, demonstrating anti-inflammatory effects in a CoV2-SP-induced scenario by inhibiting inflammatory mediators and the NLRP3 inflammasome machinery. Nanocurcumin shows promise as an anti-inflammatory product for preventing COVID-19-related airway inflammation.}, } @article {pmid37375496, year = {2023}, author = {Lafon-Hughes, L}, title = {Towards Understanding Long COVID: SARS-CoV-2 Strikes the Host Cell Nucleus.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {37375496}, issn = {2076-0817}, abstract = {Despite what its name suggests, the effects of the COVID-19 pandemic causative agent "Severe Acute Respiratory Syndrome Coronavirus-2" (SARS-CoV-2) were not always confined, neither temporarily (being long-term rather than acute, referred to as Long COVID) nor spatially (affecting several body systems). Moreover, the in-depth study of this ss(+) RNA virus is defying the established scheme according to which it just had a lytic cycle taking place confined to cell membranes and the cytoplasm, leaving the nucleus basically "untouched". Cumulative evidence shows that SARS-CoV-2 components disturb the transport of certain proteins through the nuclear pores. Some SARS-CoV-2 structural proteins such as Spike (S) and Nucleocapsid (N), most non-structural proteins (remarkably, Nsp1 and Nsp3), as well as some accessory proteins (ORF3d, ORF6, ORF9a) can reach the nucleoplasm either due to their nuclear localization signals (NLS) or taking a shuttle with other proteins. A percentage of SARS-CoV-2 RNA can also reach the nucleoplasm. Remarkably, controversy has recently been raised by proving that-at least under certain conditions-, SARS-CoV-2 sequences can be retrotranscribed and inserted as DNA in the host genome, giving rise to chimeric genes. In turn, the expression of viral-host chimeric proteins could potentially create neo-antigens, activate autoimmunity and promote a chronic pro-inflammatory state.}, } @article {pmid37373960, year = {2023}, author = {Sorokina, E and Pautova, A and Fatuev, O and Zakharchenko, V and Onufrievich, A and Grechko, A and Beloborodova, N and Chernevskaya, E}, title = {Promising Markers of Inflammatory and Gut Dysbiosis in Patients with Post-COVID-19 Syndrome.}, journal = {Journal of personalized medicine}, volume = {13}, number = {6}, pages = {}, pmid = {37373960}, issn = {2075-4426}, abstract = {Post-COVID-19 syndrome is a complex of different symptoms, which results in a multisystemic impairment after the suffering from COVID-19 infection. The aim of the study was to reveal the clinical, laboratory, and gut disorders in patients with post-COVID-19 syndrome (n = 39) before and after taking part in the 14-day complex program of rehabilitation. A complete blood count, coagulation test, blood chemistry, biomarkers, and metabolites in serum samples, and gut dysbiosis were revealed in patients on the day of admission and after 14-day rehabilitation, in comparison with the variables of healthy volunteers (n = 48) or with reference ranges. On the day of discharge, patients noted an improvement in respiratory function, general well-being, and mood. At the same time, the levels of some metabolic (4-hydroxybenzoic, succinic, fumaric acids) and inflammatory (interleukin-6) variables, which were increased on admission, did not reach the level of healthy people during the rehabilitation program. Taxonomy disbalance was observed in patients' feces, namely, a high level of total bacterial mass, a decrease in the number of Lactobacillus spp., and an increase in pro-inflammatory microorganisms. The authors suggest that the post-COVID-19 rehabilitation program should be personalized, considering the patient's state together with not only the baseline levels of biomarkers, but also with the individual taxonomy of the gut microbiota.}, } @article {pmid37373853, year = {2023}, author = {Gryglewska-Wawrzak, K and Sakowicz, A and Banach, M and Bytyçi, I and Bielecka-Dabrowa, A}, title = {Diagnostic Usefulness of Spiroergometry and Risk Factors of Long COVID in Patients with Normal Left Ventricular Ejection Fraction.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373853}, issn = {2077-0383}, support = {PMMHRI-BCO.75/2020//Polish Mother's Memorial Hospital Research Institute/ ; }, abstract = {The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic has brought forth various clinical manifestations and long-term complications, including a condition known as long COVID. Long COVID refers to a persistent set of symptoms that continue beyond the acute phase of the disease. This study investigated the risk factors and the utility of spiroergometry parameters for diagnosing patients with long COVID symptoms. The 146 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with normal left ventricular ejection fraction and without respiratory diseases were included and divided into two groups: the group demonstrating long COVID symptoms [n = 44] and the group without long COVID symptoms [n = 102]. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. ClinicalTrials.gov Identifier: NCT04828629. Patients with long COVID symptoms had significantly higher age [58 (vs.) 44 years; p < 0.0001], metabolic age [53 vs. 45 years; p = 0.02)], left atrial diameter (LA) [37 vs. 35 mm; p = 0.04], left ventricular mass index (LVMI) [83 vs. 74 g/m[2], p = 0.04], left diastolic filling velocity (A) [69 vs. 64 cm/s, p = 0.01], the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') [7.35 vs. 6.05; p = 0.01], and a lower ratio of early to late diastolic transmitral flow velocity (E/A) [1.05 vs. 1.31; p = 0.01] compared to the control group. In cardiopulmonary exercise testing (CPET), long COVID patients presented lower forced vital capacity (FVC) [3.6 vs. 4.3 L; p < 0.0001], maximal oxygen consumption measured during incremental exercise indexed per kilogram (VO2max) [21 vs. 23 mL/min/kg; p = 0.04], respiratory exchange ratio (RER) [1.0 vs. 1.1; p = 0.04], forced expiratory volume in one second (FEV1) [2.90 vs. 3.25 L; p = 0.04], and a higher ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) [106 vs. 100%; p = 0.0002]. The laboratory results pointed out that patients with long COVID symptoms also had a lower rate of red blood cells (RBC) [4.4 vs. 4.6 × 10[6]/uL; p = 0.01]; a higher level of glucose [92 vs. 90 mg/dL; p = 0.03]; a lower glomerular filtration rate (GFR) estimate by Modification of Diet in Renal Disease (MDRD) [88 vs. 95; p = 0.03]; and a higher level of hypersensitive cardiac Troponin T (hs-cTnT) [6.1 vs. 3.9 pg/mL; p = 0.04]. On the multivariate model, only FEV1/FVC% (OR 6.27, 95% CI: 2.64-14.86; p < 0.001) independently predicted the long COVID symptoms. Using the ROC analysis, the FEV1/FVC% ≥ 103 was the most powerful predictor of spiroergometry parameters (0.67 sensitive, 0.71 specific, AUC of 0.73; p < 0.001) in predicting the symptoms of long COVID. Spiroergometry parameters are useful in diagnosing long COVID and differentiating it from cardiovascular disease.}, } @article {pmid37373850, year = {2023}, author = {Badenes Bonet, D and Caguana Vélez, OA and Duran Jordà, X and Comas Serrano, M and Posso Rivera, M and Admetlló, M and Herranz Blasco, A and Cuadrado Godia, E and Marco Navarro, E and Martin Ezquerra, G and Pineiro Aguin, Z and Cumpli Gargallo, MC and Gonzalez Garcia, JG and Balcells Vilarnau, E and Rodriguez Chiaradia, D and Castells, X and Gea, J and Horcajada, JP and Villar-García, J and , }, title = {Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373850}, issn = {2077-0383}, abstract = {BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC) infection have caused a significant impact on our health system, but there is limited evidence of approved drugs focused on its prevention. Our objective was to identify risk factors that can determine the presence of PASC, with special attention to the treatment received in the acute phase, and to describe the profile of persistent symptoms in a multidisciplinary Post-Coronavirus Disease-19 (COVID-19) Unit.

METHODS: This one-year prospective observational study included patients following an acute COVID-19 infection, irrespective of whether they required hospital admission. A standardized symptom questionnaire and blood sampling were performed at the first follow-up visit, and demographic and clinical electronic data were collected. We compared subjects with PASC with those who had fully recovered. Multivariate logistic regression was performed to identify factors associated with PASC in hospitalized patients, and Kaplan-Meier curves were used to assess duration of symptoms according to disease severity and treatments received in the acute phase.

RESULTS: 1966 patients were evaluated; 1081 had mild disease, 542 moderate and 343 severe; around one third of the subjects had PASC, and were more frequently female, with obesity, asthma, and eosinophilia during acute COVID-19 disease. Patients who received treatment with dexamethasone and remdesivir during the course of the acute illness showed a lower median duration of symptoms, compared with those who received none of these treatments.

CONCLUSION: Treatment with dexamethasone and/or remdesivir may be useful to reduce the impact of PASC secondary to SARS-CoV-2 infection. In addition, we identified female gender, obesity, asthma, and disease severity as risk factors for having PASC.}, } @article {pmid37373660, year = {2023}, author = {Steinmetz, A and Gross, S and Lehnert, K and Lücker, P and Friedrich, N and Nauck, M and Bahlmann, S and Fielitz, J and Dörr, M}, title = {Longitudinal Clinical Features of Post-COVID-19 Patients-Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373660}, issn = {2077-0383}, support = {LAGuS/MV-6-SF915-0002/23//University board founds and since January 2023, the state government of Mecklenburg-Vorpommern/ ; }, abstract = {Post-COVID-19 syndrome (PCS) has been described as 'the pandemic after the pandemic' with more than 65 million people worldwide being affected. The enormous range of symptoms makes both diagnosis complex and treatment difficult. In a post-COVID rehabilitation outpatient clinic, 184 patients, mostly non-hospitalized, received a comprehensive, interdisciplinary diagnostic assessment with fixed follow-up appointments. At baseline, three in four patients reported more than 10 symptoms, the most frequent symptoms were fatigue (84.9%), decreased physical capacity (83.0%), tiredness (81.1%), poor concentration (73.6%), sleeping problems (66.7%) and shortness of breath (67.3%). Abnormalities were found in the mean values of scores for fatigue (FAS = 34.3), cognition (MoCA = 25.5), psychological alterations (anxiety, depression, post-traumatic stress disorder), limitation of lung function (CAT) and severity scores for PCS (PCFS, MCRS). Clinical abnormalities were found in elevated values of heart rate, breathing rate at rest, blood pressure and NT-proBNP levels. As the frequency of the described symptoms decreases only slowly but most often significantly over the course, it is important to monitor the patients over a longer period of time. Many of them suffer from an immense symptom burden, often without pre-existing clinical correlates. Our results show a clear association with objectifiable assessments and tests as well as pronounced symptoms.}, } @article {pmid37373611, year = {2023}, author = {Scarselli, V and Calderoni, D and Terrinoni, A and Davico, C and Pruccoli, G and Denina, M and Carducci, C and Smarrazzo, A and Martucci, M and Presicce, M and Marcotulli, D and Arletti, L and Ferrara, M and Garazzino, S and Mariani, R and Campana, A and Vitiello, B}, title = {A Neuropsychiatric Assessment of Children with Previous SARS-CoV-2 Infection.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373611}, issn = {2077-0383}, abstract = {AIM: Concerns have been raised about possible neuropsychiatric sequelae of COVID-19. The objective of this study was to examine the plausibility of long-term mental health consequences of COVID-19 by assessing a sample of children after the resolution of the acute SARS-CoV-2 infection.

METHOD: As part of a systematic follow-up assessment of pediatric patients with COVID-19 conducted at two university children's hospitals, 50 children (56% males) aged 8 to 17 years (median 11.5), 26% with previous multisystem inflammatory syndrome in children (MIS-C), without a prior history of neuropsychiatric disorders, received a battery of clinical neuropsychiatric and neuropsychological rating scales that included the Pediatric Migraine Disability Assessment (PedMIDAS), Sleep Disturbance Scale for Children (SDSC), Multidimensional Anxiety Scale for Children (MASC-2), Child Depression Inventory (CDI-2), Child Behavior Checklist (CBCL), and the NEPSY II (Neuropsychological Assessment, Second Edition). The assessments were conducted between 1 and 18 months (median 8 months) after the acute infection.

RESULTS: The CBCL internalizing symptoms score was in the clinical range for 40% of the participants (vs. a population expected rate of about 10%, p < 0.001). A sleep disturbance was detected in 28%, clinically significant anxiety in 48%, and depressive symptoms in 16%. The NEPSY II scores showed impairment in attention and other executive functions in 52%, and memory deficits in 40% of the children.

CONCLUSIONS: These data from direct assessment of a sample of children who had SARS-CoV-2 infection show higher than expected rates of neuropsychiatric symptoms, thus supporting the possibility that COVID-19 may have mental health sequelae long after the resolution of the acute infection.}, } @article {pmid37373377, year = {2023}, author = {Asanin, M and Ercegovac, M and Krljanac, G and Djukic, T and Coric, V and Jerotic, D and Pljesa-Ercegovac, M and Matic, M and Milosevic, I and Viduljevic, M and Stevanovic, G and Ranin, J and Simic, T and Bukumiric, Z and Savic-Radojevic, A}, title = {Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {12}, pages = {}, pmid = {37373377}, issn = {1422-0067}, support = {Project No. 7546803//Special Research Program on COVID-19, entitled AntioxIdentification, Science Fund of the Republic of Serbia./ ; }, mesh = {Humans ; *Antioxidants ; Post-Acute COVID-19 Syndrome ; NF-E2-Related Factor 2 ; *COVID-19/diagnostic imaging/genetics ; Glutathione Peroxidase/genetics/metabolism ; Glutathione Peroxidase GPX1 ; Superoxide Dismutase/metabolism ; Echocardiography ; }, abstract = {Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.}, } @article {pmid37373021, year = {2023}, author = {Ignatz, RM and Zirkenbach, VA and Kaya, M and Stroikova, V and Öttl, R and Frey, N and Kaya, Z}, title = {No Evidence for Myocarditis or Other Organ Affection by Induction of an Immune Response against Critical SARS-CoV-2 Protein Epitopes in a Mouse Model Susceptible for Autoimmunity.}, journal = {International journal of molecular sciences}, volume = {24}, number = {12}, pages = {}, pmid = {37373021}, issn = {1422-0067}, mesh = {Mice ; Humans ; Animals ; SARS-CoV-2 ; Autoimmunity ; *COVID-19 ; *Myocarditis/etiology ; Epitopes ; Post-Acute COVID-19 Syndrome ; Peptides ; *Autoimmune Diseases/etiology ; Inflammation ; }, abstract = {After Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed into a global pandemic, not only the infection itself but also several immune-mediated side effects led to additional consequences. Immune reactions such as epitope spreading and cross-reactivity may also play a role in the development of long-COVID, although the exact pathomechanisms have not yet been elucidated. Infection with SARS-CoV-2 can not only cause direct damage to the lungs but can also lead to secondary indirect organ damage (e.g., myocardial involvement), which is often associated with high mortality. To investigate whether an immune reaction against the viral peptides can lead to organ affection, a mouse strain known to be susceptible to the development of autoimmune diseases, such as experimental autoimmune myocarditis (EAM), was used. First, the mice were immunized with single or pooled peptide sequences of the virus's spike (SP), membrane (MP), nucleocapsid (NP), and envelope protein (EP), then the heart and other organs such as the liver, kidney, lung, intestine, and muscle were examined for signs of inflammation or other damage. Our results showed no significant inflammation or signs of pathology in any of these organs as a result of the immunization with these different viral protein sequences. In summary, immunization with different SARS-CoV-2 spike-, membrane-, nucleocapsid-, and envelope-protein peptides does not significantly affect the heart or other organ systems adversely, even when using a highly susceptible mouse strain for experimental autoimmune diseases. This suggests that inducing an immune reaction against these peptides of the SARS-CoV-2 virus alone is not sufficient to cause inflammation and/or dysfunction of the myocardium or other studied organs.}, } @article {pmid37372794, year = {2023}, author = {Romero-Rodríguez, E and Vélez-Santamaría, R and Pérula-de-Torres, LÁ and González-Lama, J and Castro-Jiménez, RÁ and Simón-Vicente, L and Jiménez-García, C and González-Bernal, JJ and Santamaría-Peláez, M and Fernández-Solana, J and González-Santos, J}, title = {Clinical and Epidemiological Profiles of Primary Healthcare Professionals with COVID-19 Infection and Long COVID: An Observational Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, pmid = {37372794}, issn = {2227-9032}, support = {EXP. No. AP-0184-2021-C2-F2//Progreso y Salud Foundation of the Ministry of Health and Families of the Junta de Andalucía/ ; }, abstract = {Health professionals have been one of the groups most affected by the SARS-CoV-2 virus. Currently, there is little scientific evidence on the similarities and differences between COVID-19 infection and the development of long COVID in primary care (PC) workers. Therefore, it is necessary to analyse their clinical and epidemiological profiles in depth. This study was observational and descriptive, including PC professionals who were divided into three comparison groups based on the diagnostic test for acute SARS-CoV-2 infection. The responses were analysed using descriptive and bivariate analysis to examinate the relationship between independent variables and the presence or not of long COVID. Binary logistic regression analysis was also conducted, with each symptom as the dependent variable and each group as the independent variable. The results describe the sociodemographic characteristics of these population groups, revealing that women in the health sector are the most affected by long COVID and that being in this group is associated with its development. Furthermore, individuals with long COVID exhibited the highest number of symptoms and pathologies. Certain symptoms were found to be associated with long COVID development in this population, including an altered sense of smell, pneumonia, fever, and sore throat, among others. Similarly, altered senses of smell and taste, chest tightness, and joint pain, among others, were found to be associated with acute COVID-19 infection. Additionally, patients with pre-existing overweight or obesity were more likely to experience acute COVID-19 and develop long COVID. The data obtained can be crucial for improving the detection, diagnosis, and treatment of long COVID patients, ultimately leading to an enhancement in their quality of life.}, } @article {pmid37371263, year = {2023}, author = {Al-Shamrani, A and Al-Shamrani, K and Al-Otaibi, M and Alenazi, A and Aldosaimani, H and Aldhalaan, Z and Alalkami, H and Yousef, AA and Kobeisy, S and Alharbi, S}, title = {Residual Cough and Asthma-like Symptoms Post-COVID-19 in Children.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {37371263}, issn = {2227-9067}, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and is characterized by different presentations ranging from asymptomatic to severe pneumonia. COVID-19 affects all age groups, including pediatric patients. We observed numerous children complaining of a cough post-COVID-19, even if it was trivial. The most reported persistent symptoms after recovery from COVID-19 were insomnia, coughing, fatigue, dyspnea, loss of taste and/or smell, and headache. To date, residual cough post-COVID-19 has been reported in pediatrics and adolescents.

METHOD: we conducted a retrospective study, with a self-administered questionnaire by the patient or caregiver, 12 months post-COVID-19-infection.

RESULT: A total of 94.8% of patients were Saudi citizens and were mainly from the southern region of Saudi Arabia (50.0%). Mothers (64.4%) submitted most of the results. The ages were as follows: 6-14 years (51.0%), 3-5 years (32.3%), and younger than 2 years of age (only 16.7%). Females accounted for 41.7% of those studied. Nearly half of the patients (48.5%) had had a previous COVID-19 infection in 2022, with only 2.1% infected in 2019. Only 27/194 (13.9%) patients required hospital admission, and 7 of them (4.2%) required intensive care treatment. A total of 179 (92.2%) patients still reported persistent symptoms 4 weeks post-COVID-19-infection. A cough was reported in 69.8% of patients, followed by cough and wheezing in 12.3%. The cough was described as dry in 78.0% and nocturnal in 54.1%, while 42.5% did not notice any diurnal variation. For those reporting residual cough, 39.3% found that it affected school attendance and daily activities, 31.1% reported associated chest pain, 51.9% associated it with wheezing, and 27.1% associated it with shortness of breath. For 54.4%, the residual cough lasted less than one month, while 31.4% reported a 1-2 month duration. Only 1.0% had a duration of cough of more than 3 months. For cough relief, 28.2% used bronchodilators, 19.9% used cough syrup, 16.6% used a combination of bronchodilators and steroid inhalers, and 1.7% used antibiotics. Surprisingly, 33% attempted herbal remedies for cough relief. Sesame oil was used the most (40.0%), followed by a mixture of olive oil and sesame oil (25.0%), and 21.7% used male frankincense. The majority (78.4%) sought medical advice for their post-infection cough, either from general pediatricians (39.5%) or via specialist pediatric pulmonology consultations (30.9%). A total of 11.0% with a residual cough reported having pets at home, while 27.2% reported secondhand smoke exposure in the household. Before infection with COVID-19, only 32.6% were diagnosed with asthma, while 68.2% reported a diagnosis of atopic skin.

CONCLUSIONS: There was a high prevalence of residual cough post-COVID-19, extended for a minimum of two months, and the characteristics of the cough were very similar to those of asthmatic patients. There was still a high prevalence of using cough syrup and herbal remedies, especially olive oil, sesame oil, and male frankincense. A residual cough adversely affected school attendance in daily activities, and there was a high prevalence of other siblings in the family being affected. The study showed that a minority of patients were seen by the pulmonologist; luckily, long COVID was rare in our study, and so further studies are highly needed to confirm the association with asthma. More educational programs are highly needed regarding herbal remedies and cough syrup.}, } @article {pmid37370884, year = {2023}, author = {Sansone, F and Pellegrino, GM and Caronni, A and Bonazza, F and Vegni, E and Lué, A and Bocci, T and Pipolo, C and Giusti, G and Di Filippo, P and Di Pillo, S and Chiarelli, F and Sferrazza Papa, GF and Attanasi, M}, title = {Long COVID in Children: A Multidisciplinary Review.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, pmid = {37370884}, issn = {2075-4418}, support = {NA//University of Milan/ ; }, abstract = {Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.}, } @article {pmid37370581, year = {2023}, author = {Cerfoglio, S and Capodaglio, P and Rossi, P and Verme, F and Boldini, G and Cvetkova, V and Ruggeri, G and Galli, M and Cimolin, V}, title = {Tele-Rehabilitation Interventions for Motor Symptoms in COVID-19 Patients: A Narrative Review.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {37370581}, issn = {2306-5354}, abstract = {The COVID-19 pandemic brought new challenges to global healthcare systems regarding the care of acute patients and the delivery of rehabilitation programs to post-acute or chronic patients. Patients who survive severe forms of COVID-19 often report incomplete healing and long-term symptoms. The need of these patients for rehabilitation has been recognized as a public health problem. In this context, the application of tele-rehabilitation has been explored to reduce the burden on healthcare systems. The purpose of this narrative review is to present an overview of the state of the art regarding the application of remote motor rehabilitation programs for paucisymptomatic acute and post-acute COVID-19 patients, with a focus on the motor aspects of tele-rehabilitation. Following an extensive search on PubMed, the Web of Science, and Scopus, specific studies have been reviewed and compared in terms of study objectives and participants, experimental protocols and methods for home-based interventions, functional assessment, and rehabilitation outcomes. Overall, this review suggests the feasibility and the effectiveness of tele-rehabilitation as a promising tool to complement face-to-face rehabilitation interventions. However, further improvements are needed to overcome the limitations and the current lack of knowledge in the field.}, } @article {pmid37369791, year = {2023}, author = {Marshall, M}, title = {Long COVID: answers emerge on how many people get better.}, journal = {Nature}, volume = {619}, number = {7968}, pages = {20}, pmid = {37369791}, issn = {1476-4687}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/epidemiology/prevention & control/therapy ; }, } @article {pmid37368329, year = {2023}, author = {Fesharaki Zadeh, A and Arnsten, AFT and Wang, M}, title = {Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.}, journal = {Neurology international}, volume = {15}, number = {2}, pages = {725-742}, pmid = {37368329}, issn = {2035-8385}, support = {P30 AG066508/AG/NIA NIH HHS/United States ; R01 AG061190/AG/NIA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, abstract = {Sustained cognitive deficits are a common and debilitating feature of "long COVID", but currently there are no FDA-approved treatments. The cognitive functions of the dorsolateral prefrontal cortex (dlPFC) are the most consistently afflicted by long COVID, including deficits in working memory, motivation, and executive functioning. COVID-19 infection greatly increases kynurenic acid (KYNA) and glutamate carboxypeptidase II (GCPII) in brain, both of which can be particularly deleterious to PFC function. KYNA blocks both NMDA and nicotinic-alpha-7 receptors, the two receptors required for dlPFC neurotransmission, and GCPII reduces mGluR3 regulation of cAMP-calcium-potassium channel signaling, which weakens dlPFC network connectivity and reduces dlPFC neuronal firing. Two agents approved for other indications may be helpful in restoring dlPFC physiology: the antioxidant N-acetyl cysteine inhibits the production of KYNA, and the α2A-adrenoceptor agonist guanfacine regulates cAMP-calcium-potassium channel signaling in dlPFC and is also anti-inflammatory. Thus, these agents may be helpful in treating the cognitive symptoms of long COVID.}, } @article {pmid37367456, year = {2023}, author = {Shelkovnikova, TA and Maksimova, AS and Ryumshina, NI and Mochula, OV and Vaizov, VK and Ussov, WY and Anfinogenova, ND}, title = {Transformative Effect of COVID-19 Pandemic on Magnetic Resonance Imaging Services in One Tertiary Cardiovascular Center.}, journal = {Journal of imaging}, volume = {9}, number = {6}, pages = {}, pmid = {37367456}, issn = {2313-433X}, support = {22-I5-00313//The Russian Science Foundation/ ; }, abstract = {The aim of study was to investigate the transformative effect of the COVID-19 pandemic on magnetic resonance imaging (MRI) services in one tertiary cardiovascular center. The retrospective observational cohort study analyzed data of MRI studies (n = 8137) performed from 1 January 2019 to 1 June 2022. A total of 987 patients underwent contrast-enhanced cardiac MRI (CE-CMR). Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. The annual absolute numbers and rates of CE-CMR procedures in our center significantly increased from 2019 to 2022 (p-value < 0.05). The increasing temporal trends were observed in hypertrophic cardiomyopathy (HCMP) and myocardial fibrosis (p-value < 0.05). The CE-CMR findings of myocarditis, acute myocardial infarction, ischemic cardiomyopathy, HCMP, postinfarction cardiosclerosis, and focal myocardial fibrosis prevailed in men compared with the corresponding values in women during the pandemic (p-value < 0.05). The frequency of myocardial fibrosis occurrence increased from ~67% in 2019 to ~84% in 2022 (p-value < 0.05). The COVID-19 pandemic increased the need for MRI and CE-CMR. Patients with a history of COVID-19 had persistent and newly occurring symptoms of myocardial damage, suggesting chronic cardiac involvement consistent with long COVID-19 requiring continuous follow-up.}, } @article {pmid37366496, year = {2023}, author = {Kerksieck, P and Ballouz, T and Haile, SR and Schumacher, C and Lacy, J and Domenghino, A and Fehr, JS and Bauer, GF and Dressel, H and Puhan, MA and Menges, D}, title = {Post COVID-19 condition, work ability and occupational changes in a population-based cohort.}, journal = {The Lancet regional health. Europe}, volume = {31}, number = {}, pages = {100671}, pmid = {37366496}, issn = {2666-7762}, abstract = {BACKGROUND: Evidence on the impact of post COVID-19 condition (PCC) on work ability is limited but critical due to its high prevalence among working-age individuals. This study aimed to evaluate the association between PCC, work ability, and occupational changes in a population-based cohort.

METHODS: We used data from working-age adults included in a prospective, longitudinal cohort of a random sample of all individuals infected with SARS-CoV-2 between August 2020 and January 2021 in the Canton of Zurich, Switzerland. We evaluated current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), and PCC-related occupational changes one year after infection.

FINDINGS: Of 672 individuals included in this study, 120 (17.9%) were categorised as having PCC (defined as presence of self-reported COVID-19 related symptoms) at 12 months. There was very strong evidence that current work ability scores were mean 0.62 (95% CI 0.30-0.95) points lower among those with PCC compared to those without in adjusted regression analyses. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (adjusted odds ratio (aOR) 0.30, 95% CI 0.20-0.46) and mental (aOR 0.40, 0.27-0.62) demands in individuals with PCC. Higher age and history of psychiatric diagnosis were associated with more substantial reductions in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce.

INTERPRETATION: These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity.

FUNDING: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.}, } @article {pmid37364827, year = {2023}, author = {Mortazavi, S and de Peralta-Venturina, M and Marchevsky, AM}, title = {Nonspecific interstitial pneumonia pattern is a frequent finding in patients with post-acute COVID-19 syndrome treated with bilateral orthotopic lung transplantation: current best evidence.}, journal = {Human pathology}, volume = {141}, number = {}, pages = {90-101}, pmid = {37364827}, issn = {1532-8392}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/pathology ; *Idiopathic Interstitial Pneumonias/pathology ; *Lung Diseases, Interstitial/etiology/surgery/diagnosis ; Lung/surgery/pathology ; *Lung Transplantation/adverse effects ; *Cysts/pathology ; Fibrosis ; }, abstract = {Patients with post-acute COVID-19 (PA-COVID) syndrome or long COVID-19 syndrome develop persistent symptoms and complications that last beyond 4 weeks of the initial infection. There is limited information regarding the pulmonary pathology in PA-COVID patients who require bilateral orthotopic lung transplantation (BOLT). Our experience with 40 lung explants from 20 PA-COVID patients who underwent BOLT is described. Clinicopathologic findings are correlated with best evidence from literature. The lung parenchyma showed bronchiectasis (n = 20) and severe interstitial fibrosis with areas resembling the nonspecific interstitial pneumonia (NSIP) pattern of fibrosis (n = 20), interstitial fibrosis not otherwise specified (n = 20), and fibrotic cysts (n = 9). None of the explants exhibited a usual interstitial pneumonia pattern of fibrosis. Other parenchymal changes included multinucleated giant cells (n = 17), hemosiderosis (n = 16), peribronchiolar metaplasia (n = 19), obliterative bronchiolitis (n = 6), and microscopic honeycombing (n = 5). Vascular abnormalities included thrombosis of a lobar artery (n = 1) and microscopic thrombi in small vessels (n = 7). Systematic literature review identified 7 articles reporting the presence in 12 patients of interstitial fibrosis showing the NSIP pattern (n = 3), organizing pneumonia/diffuse alveolar damage (n = 4) and not otherwise specified (n = 3) patterns. All but one of these studies also reported the presence of multinucleated giant cells and none of the studies reported the presence of severe vascular abnormalities. PA-COVID patients undergoing BOLT show a pattern of fibrosis that resembles a mixed cellular-fibrotic NSIP pattern and generally lack severe vascular complications. As the NSIP pattern of fibrosis is often associated with autoimmune diseases, additional studies are needed to understand the mechanism of disease and learn whether this information can be used for therapeutic purposes.}, } @article {pmid37364815, year = {2023}, author = {Bernal, KDE and Whitehurst, CB}, title = {Incidence of Epstein-Barr virus reactivation is elevated in COVID-19 patients.}, journal = {Virus research}, volume = {334}, number = {}, pages = {199157}, pmid = {37364815}, issn = {1872-7492}, mesh = {Humans ; *Epstein-Barr Virus Infections/complications ; Herpesvirus 4, Human/genetics ; Incidence ; Post-Acute COVID-19 Syndrome ; Virus Activation ; *COVID-19 ; SARS-CoV-2 ; }, abstract = {COVID-19, an infectious respiratory illness, is caused by infection with the SARS-CoV-2 virus. Individuals with underlying medical conditions are at increased risk of developing serious illnesses such as long COVID. Recent studies have observed Epstein-Barr virus (EBV) reactivation in patients with severe illness or long COVID, which may contribute to associated symptoms. We determined the frequency of EBV reactivation in COVID-19 positive patients compared to COVID-19 negative patients. 106 blood plasma samples were collected from COVID-19 positive and negative patients and EBV reactivation was determined by detection of EBV DNA and antibodies against EBV lytic genes in individuals with previous EBV infection. 27.1% (13/48) of EBV reactivations, based on qPCR detection of EBV genomes, are from the COVID positive group while only 12.5% (6/48) of reactivations belonged to the negative group. 20/52 (42.30%) of the COVID PCR negative group had detectable antibodies against SARS-CoV-2 nucleoprotein (Np); indicative of past infection. A significantly higher SARS-CoV-2 Np protein level was found in the COVID-19 positive group. In conclusion, COVID-19 patients experienced increased reactivation of EBV in comparison to COVID negative patients.}, } @article {pmid37363499, year = {2023}, author = {Ali, M and Mehjabin, T}, title = {Prevalence and predictors of neck pain among Bangladeshi community dwellers during COVID-19 pandemic: analysis of a matched case-control data.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {6}, pages = {2304-2312}, pmid = {37363499}, issn = {2049-0801}, abstract = {UNLABELLED: Extant literature has established a significant association between COVID-19 and musculoskeletal health complaints. Despite this, there remains a paucity of data regarding the relationship between COVID-19 and neck pain among community-dwelling individuals. The primary objective of this study was to ascertain the prevalence and predictors of neck pain in this population in Bangladesh. This was achieved via screening the musculoskeletal health of post-acute COVID-19 survivors and their age and sex-matched unaffected counterparts.

METHODS: This study employs a case-control design and includes 878 Bangladeshi individuals aged 18 years or older, of which 439 were post-acute COVID-19 patients. Data were collected between 24 February and 7 April 2022. Neck pain was assessed using the musculoskeletal subscale of subjective health complaints. Descriptive analysis was conducted to determine the prevalence of neck pain and to compare its prevalence across subgroups. Furthermore, multiple logistic regression analysis was utilized to identify the predictors of neck pain.

RESULTS: Out of 878 participants, 15.1% reported experiencing neck pain. However, neck pain was significantly higher among those with post-acute COVID-19 than those without the infection (21.4% vs. 8.9%, P<0.001). An adjusted analysis found that COVID-19 infection was independently associated with neck pain (adjusted odds ratio=2.626%, 95% CI=1.666-4.140).

CONCLUSION: The results of this study suggest a link between COVID-19 and neck pain. Therefore, it is recommended that healthcare service providers are prepared to manage the increased incidence of neck pain among patients who have recovered from COVID-19.}, } @article {pmid37363407, year = {2023}, author = {Feng, BW and Rong, PJ}, title = {Acupoint stimulation for long COVID: A promising intervention:.}, journal = {World journal of acupuncture-moxibustion}, volume = {}, number = {}, pages = {}, pmid = {37363407}, issn = {1003-5257}, abstract = {"Long COVID" is a sustained symptom following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to recent statistics, at least 65 million people have long COVID, which poses a long-term threat to human health. The pathogenic mechanisms of coronavirus disease 2019 (COVID-19) are complex and affect multiple organs and systems. Common symptoms include palpitations, breathing difficulties, attention and memory deficits, fatigue, anxiety, and depression. It is difficult to achieve satisfactory treatment effect with a single intervention. Currently, treatment strategies for long COVID are still in the exploratory stage, and there is an urgent need to find appropriate and effective methods for long COVID treatment. Traditional Chinese medicine is effective in treating the various phases of COVID-19. Previous studies have shown that acupoint stimulation therapy is effective in improving palpitations, dyspnea, cognitive impairment, anxiety, depression, and other symptoms in patients. According to previous studies, acupoint stimulation may improve various symptoms related to long COVID. This paper discusses the potential application value of acupoint stimulation in the treatment of long COVID-related symptoms, based on the common sequelae of various systems involved in long COVID, and the effect of acupoint stimulation in the treatment of similar symptoms and diseases in recent years.}, } @article {pmid37363406, year = {2023}, author = {Li, BB and Feng, CW and Qu, YY and Sun, ZR and Chen, T and Wang, YL and Wang, QY and Lu, J and Shao, YY and Yang, TS}, title = {Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.}, journal = {World journal of acupuncture-moxibustion}, volume = {}, number = {}, pages = {}, pmid = {37363406}, issn = {1003-5257}, abstract = {Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.}, } @article {pmid37363273, year = {2023}, author = {Ali, RN and Sarkar, S}, title = {Impact of opinion dynamics on the public health damage inflicted by COVID-19 in the presence of societal heterogeneities.}, journal = {Frontiers in digital health}, volume = {5}, number = {}, pages = {1146178}, pmid = {37363273}, issn = {2673-253X}, abstract = {INTRODUCTION: Certain behavioral practices, such as wearing masks, practicing social distancing, and accepting vaccines, play a crucial role in impeding the spread of COVID-19 and reducing the severity of symptoms. Opinions regarding whether to observe such behavioral practices evolve over time through interactions via networks that overlap with but are not identical to the physical interaction networks over which the disease progresses. This necessitates the joint study of the dynamics of COVID-19 and opinion evolution.

METHODS: We develop a mathematical model that can be easily adapted to a wide range of behavioral practices and captures in a computationally tractable manner the joint evolution of the disease and relevant opinions in populations of large sizes. Populations of large sizes are typically heterogeneous in that they comprise individuals of different age groups, genders, races, and underlying health conditions. Such groups have different propensities to imbibe severe forms of the disease, different physical contact, and social interaction patterns and rates. These lead to different disease and opinion dynamics in them. Our model is designed to effectively capture such diversities.

RESULTS: Computations using our model reveal that opinion dynamics have a strong impact on fatality and hospitalization counts and the number of man-days lost due to symptoms both in the regular form of the disease and the extended forms, more commonly known as long COVID. We show that opinion dynamics in certain groups have a disproportionate impact on the overall public health attributes because they have high physical interaction rates, even when they have the lowest propensity to imbibe severe forms of the disease. This identifies a social vulnerability that malactors can utilize to inflict heavy public health damages through opinion campaigns targeting specific segments. Once such vulnerabilities are identified, which we accomplish, adequate precautions may be designed to enhance resilience to such targeted attacks and better protect public health.

DISCUSSION: By recognizing and understanding the vulnerabilities, appropriate precautions can be developed to enhance resilience against targeted attacks and safeguard public health. Our study underscores the importance of considering opinion evolution alongside disease dynamics, providing insights into the interplay between behavioral practices, opinions, and disease outcomes. We believe that our model is a valuable tool for understanding the joint dynamics of COVID-19 and opinions. We hope that our findings will help to inform public health policy and facilitate evidence-based decision-making for public health interventions.}, } @article {pmid37363156, year = {2023}, author = {Lemogne, C and Ranque, B}, title = {[Role of psychological factors in post-COVID-19 condition].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {}, number = {}, pages = {}, pmid = {37363156}, issn = {0001-4079}, abstract = {Even after a mild episode of coronavirus disease 2019 (COVID-19), many patients suffer from persistent symptoms that can impair their quality of life for months. The potential role of psychological mechanisms in this post-COVID-19 condition, often referred to as long COVID, has been discussed early in the pandemic. Evidence supporting this hypothesis is now accumulating. First, a history of anxiety or depression is now an established risk factor for post-COVID-19 condition with a dose-response relationship and effect size similar to those of other known risk factors. This association extends to other forms of psychological distress, including perceived stress and loneliness. Second, specific beliefs about COVID-19 have been associated with the risk of subsequent similar symptoms, occurring weeks to several months later. Other studies, which have yet to be replicated, suggest an influence of the context of the initial infection (first versus second wave of the pandemic, before the emergence of significant variants and vaccination) and the trust in various sources of information about COVID-19 on the risk of subsequent symptoms. Bayesian models of perception can account for these results particularly well within a theoretical framework similar to that advanced for functional somatic disorders, integrating increased symptom expectations with decreased perception of the body internal state (interoception) and intolerance of uncertainty in the context of symptoms initially triggered by an infectious episode. These psychological mechanisms should obviously not be considered as exclusive. However, since they are modifiable, they could be targeted in clinical trials, within an integrative and multidisciplinary approach.}, } @article {pmid37363154, year = {2023}, author = {Chollet, F and Planton, M and Sailler, L and De Almeida, S and Alvarez, M and Pariente, J}, title = {[Neurological forms of long COVID in adults: Critical approach].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {}, number = {}, pages = {}, pmid = {37363154}, issn = {0001-4079}, abstract = {Now recognized by health authorities, long COVID is identified as a frequent condition complicating the evolution of SARS-CoV-2 infection. Its polymorphic and sometimes disconcerting clinical expression raises questions about its mechanism. Patterns of clinical expression suggest extensive involvement of the nervous system through an almost ubiquitous cognitive complaint. This article reviews the neurological symptoms and forms of these patients, and the neuropsychological explorations aimed at objectifying a cognitive deficit. The studies published until now confronted with the clinical mode of expression, did not make it possible to define a deficit neuropsychological profile at the level of the groups, and evoked more a functional impairment than a lesion. However, each series mentions a small number of patients in whom a cognitive deficit is objectified. The uncertainties about the causes of the prolonged forms of COVID, the heterogeneity of the published studies, and the virtual absence of temporal evolution data should make one cautious about the interpretation of these data but should in no way delay or prevent taking into account care of these patients.}, } @article {pmid37362775, year = {2023}, author = {Zhang, J and Zhang, Y and Xia, Y and Sun, J}, title = {Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19.}, journal = {Genes & diseases}, volume = {11}, number = {3}, pages = {}, pmid = {37362775}, issn = {2352-3042}, abstract = {Long COVID, also known for post-acute sequelae of COVID-19, describes the people who have the signs and symptoms that continue or develop after the acute COVID-19 phase. Long COVID patients suffer from an inflammation or host responses towards the virus approximately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an uncharacterized duration. Anyone infected with COVID-19 before could experience long-COVID conditions, including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early. People with long COVID may experience health problems from different types and combinations of symptoms over time, such as fatigue, dyspnea, cognitive impairments, and gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, decreased or loss of appetite, abdominal pain, and dysgeusia). The critical role of the microbiome in these GI symptoms and long COVID were reported in clinical patients and experimental models. Here, we provide an overall view of the critical role of the GI tract and microbiome in the development of long COVID, including the clinical GI symptoms in patients, dysbiosis, viral-microbiome interactions, barrier function, and inflammatory bowel disease patients with long COVID. We highlight the potential mechanisms and possible treatment based on GI health and microbiome. Finally, we discuss challenges and future direction in the long COVID clinic and research.}, } @article {pmid37360003, year = {2023}, author = {Calabrese, LH}, title = {Long COVID in inflammatory rheumatic diseases-what's in a name?.}, journal = {The Lancet. Rheumatology}, volume = {5}, number = {7}, pages = {e364-e365}, pmid = {37360003}, issn = {2665-9913}, } @article {pmid37358898, year = {2023}, author = {Angeli, F and Verdecchia, P and Reboldi, G}, title = {Long COVID [post-acute sequelae of coronavirus disease 2019]: experimental drugs for cardiopulmonary complications.}, journal = {Expert opinion on investigational drugs}, volume = {32}, number = {7}, pages = {567-570}, doi = {10.1080/13543784.2023.2230121}, pmid = {37358898}, issn = {1744-7658}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Renin-Angiotensin System ; Peptidyl-Dipeptidase A/metabolism ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Disease Progression ; }, abstract = {[Figure: see text].}, } @article {pmid37357766, year = {2023}, author = {Pérez Catalán, I and Gascón Buj, A and García Muñoz, S and Gómez Alfaro, I and Roig Martí, C and Torres García, M and Reig Valero, R and Ferrando Piqueres, R and Mateu Campos, L and Ramos Rincón, JM and Usó Blasco, J}, title = {Nirmatrelvir/ritonavir as a possible treatment for Long-COVID.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {36}, number = {5}, pages = {545-546}, pmid = {37357766}, issn = {1988-9518}, mesh = {Humans ; *Ritonavir/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Drug Treatment ; Antiviral Agents/therapeutic use ; }, } @article {pmid37357041, year = {2023}, author = {Noureddine, S and Roux-Claudé, P and Eberst, G and Westeel, V and Barnig, C and Claudé, F}, title = {[The role of the cardiopulmonary exercise test and pulmonary rehabilitation in long COVID-19].}, journal = {Revue des maladies respiratoires}, volume = {40}, number = {7}, pages = {604-622}, pmid = {37357041}, issn = {1776-2588}, mesh = {Humans ; *COVID-19 ; Exercise Test ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Dyspnea/diagnosis/etiology ; }, abstract = {INTRODUCTION: Long COVID refers to persistent symptoms, lasting more than 4 weeks after acute SARS-CoV-2 infection, even though the infection itself has been successfully controlled and remedied. Patient complaints are diverse, and the underlying physiopathological mechanisms are not well understood. Dyspnea and muscle fatigue are among the most commonly reported symptoms.

STATE OF THE ART: Cardiopulmonary exercise test (CPET) has been recognized as a useful tool in investigation of unexplained dyspnea. In patients with chronic lung disease, pulmonary rehabilitation is a program designed to counteract dyspnea, to increase exercise capacity and to improve quality of life.

PERSPECTIVES: Publications on CPET and pulmonary rehabilitation are needed in order to deepen comprehension and enhance management of long-COVID-19.

CONCLUSIONS: CPET reports have shown that symptoms persisting in the aftermath of acute SARS-CoV-2 infection may be related to deconditioning, a common occurrence after ICU stay, to cardiac dysautonomia subsequent to critical infections and, finally, to dysfunctional breathing subsequent to mild infections. These findings justify pulmonary rehabilitation, which has proven to be effective regardless of the severity of the initial infection, not only immediately after hospital discharge, but also at later points in time.}, } @article {pmid37356392, year = {2023}, author = {Glöckler, J and Mizaikoff, B and Díaz de León-Martínez, L}, title = {SARS CoV-2 infection screening via the exhaled breath fingerprint obtained by FTIR spectroscopic gas-phase analysis. A proof of concept.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {302}, number = {}, pages = {123066}, pmid = {37356392}, issn = {1873-3557}, mesh = {Humans ; Spectroscopy, Fourier Transform Infrared ; Post-Acute COVID-19 Syndrome ; Pandemics ; Breath Tests/methods ; *COVID-19 ; Nitric Oxide ; Acetaldehyde ; Biomarkers ; *Volatile Organic Compounds/analysis ; }, abstract = {The COVID-19 pandemic remains a global challenge now with the long-COVID arising. Mitigation measures focused on case counting, assessment and determination of variants and their likely targets of infection and transmission, the pursuit of drug treatments, use and enhancement of masks, social distancing, vaccination, post-infection rehabilitation, and mass screening. The latter is of utmost importance given the current scenario of infections, reinfections, and long-term health effects. Research on screening platforms has been developed to provide more sensitive, specific, and reliable tests that are accessible to the entire population and can be used to assess the prognosis of the disease as well as the subsequent health follow-up of patients with sequelae of COVID-19. Therefore, the aim of the present study was the simulation of exhaled breath of COVID-19 patients by evaluation of three identified COVID-19 indicator breath biomarkers (acetone (ACE), acetaldehyde (ACH) and nitric oxide (NO)) by gas-phase infrared spectroscopy as a proof-of-concept principle for the detection of infected patients' exhaled breath fingerprint and subsequent follow-up. The specific fingerprints of each of the compounds and the overall fingerprint were obtained. The synthetic exhaled breath evaluation concept revealed a linearity of r = 0.99 for all compounds, and LODs of 6.42, 13.81, 9.22 ppm, and LOQs of 42.26, 52.57, 69.23 ppm for NO, ACE, and ACH, respectively. This study proves the fundamental feasibility of gas-phase infrared spectroscopy for fingerprinting lung damage biomarkers in exhaled breath of patients with COVID-19. This analysis would allow faster and cheaper screening and follow-up of infected individuals, which could improve mass screening in POC settings.}, } @article {pmid37355939, year = {2022}, author = {Bhattacharyya, P and Sengupta, S and De, A and Mukherjee, S and Paul, M and Dey, D}, title = {Unsuspected Subclinical Left Ventricular Dysfunction in Post-COVID Patients: A Real-world Observation.}, journal = {The Journal of the Association of Physicians of India}, volume = {70}, number = {11}, pages = {11-12}, doi = {10.5005/japi-11001-0147}, pmid = {37355939}, issn = {0004-5772}, mesh = {Humans ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Echocardiography, Doppler ; *Ventricular Dysfunction, Left/diagnostic imaging/etiology ; *Cardiomyopathies ; *Ventricular Dysfunction, Right ; }, abstract = {BACKGROUND: Subclinical myocardial dysfunction may exist in post-COVID-19 patients and may carry significance in long term.

METHODOLOGY: Subjects of long-COVID-19 with historically and radiologically significant pulmonary involvement (without documented cardiac involvement) were evaluated on outpatient follow-up echocardiographically when they had disproportionate shortness of breath (SOB), fatigue, or high pulse rate as perceived by the physicians. The common acute-phase symptoms were noted and scored retrospectively. The assessment included spirometry and measurement of chronic obstructive pulmonary disease (COPD) assessment test (CAT) score with measurement of the left ventricular (LV) and right ventricular (RV) free wall global longitudinal strain as an adjunct to routine two-dimensional and Doppler echocardiography and spirometry. The results were evaluated statistically with respect to the history of hospitalization.

RESULTS: The hospitalized (n = 15) and nonhospitalized (n = 10) patients were demographically similar. However, the nonhospitalized patients had higher total symptom score (p = 0.03), anosmia (p = 0.017), and ageusia (p = 0.0019). At follow-up (>3 months of acute illness), the nonhospitalized patients had a better CAT score (p = 0.04), higher change in max pulse rate (p = 0.03), and higher forced expiratory volume in 1 second (FEV1) (p = 0.002), tricuspid annular plane systolic excursion (TAPSE) (p = 0.02), and left ventricular global longitudinal strain (LVGLS) (-17.15 ± 1.19 vs -13.11 ± 1.91) (p = 0.0001). Overall, the two groups formed distinct clusters. The LVGLS and the maximum pulse rate difference in the two chair test (2CT) seem to contribute maximally to the variance between the two groups in multivariate analysis.

CONCLUSION: The subclinical myocardial dysfunction persisting in post-COVID patients (without suspected cardiac affection and lower neuroinflammatory symptoms in the acute phase) with significant pulmonary affection needs further evaluation. They demonstrate a higher max pulse rate difference in the 2CT. This real-world observation demands further investigations.}, } @article {pmid37355868, year = {2022}, author = {Shah, M and Kakar, A and Gogia, A}, title = {The Hindi Version of International Consensus Criteria: A Cross-cultural Adaptation and Validation Study for Myalgic Encephalomyelitis in Post-COVID Patients.}, journal = {The Journal of the Association of Physicians of India}, volume = {70}, number = {10}, pages = {11-12}, doi = {10.5005/japi-11001-0090}, pmid = {37355868}, issn = {0004-5772}, mesh = {Humans ; Cross-Cultural Comparison ; *Fatigue Syndrome, Chronic ; Consensus ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Language ; Surveys and Questionnaires ; Reproducibility of Results ; Fatigue/etiology ; }, abstract = {CONTEXT: Fatigue is the most prominent feature of long COVID. With the increasing burden of long COVID cases post-acute phase of illness after recurrent waves of the pandemic, understanding its pathophysiology is of paramount importance. Such fatigue and post-viral illness could be associated with features of neuroimmune exhaustion and thus be a part of a larger syndrome such as myalgic encephalomyelitis (ME). Identifying the proportion of patients having ME from those experiencing fatigue would bring us one step closer to understanding the pathophysiology. International consensus criteria (ICC) originally published in English (ICC-E) is a valid and reliable tool for identifying cases of ME. However, a validated Hindi version of ICC-E is not available. : To develop and validate an equivalent version of ICC-E in the native Hindi language (ICC-H) to suit Indian patients and health care workers even at peripheries and to make conducting large scales surveys more feasible.

SUBJECTS AND METHODS: Once permission from the ethics board was granted, guidelines given by MAPI Research Trust were followed and ICC-H was developed from ICC-E, in the following steps: (a) translation to Hindi, (b) back translation, (c) comparison between the translated and back-translated version performed by experts, and (d) pre-pilot test in the intended population. The ICC-H was applied to 53 bilingual individuals knowing both Hindi and English.

STATISTICAL ANALYSIS USED: The distribution of Hindi and English questionnaires was analyzed using the Chi-square test and Spearman's correlation coefficient was used for correlation between answers of each question.

RESULTS: The score of individual items and its global score was highly correlated with each other (p<0.001). The scores of individual components and global scores of ICC-H at baseline and original ICC-E after 4 weeks did not differ significantly.

CONCLUSION: This study shows that the ICC-H is a valid and reliable instrument for the assessment of ME. ICC-H can be used for Hindi speaking population for identifying cases of ME. Key Messages There is a significant overlap in symptoms of long COVID and ME, with fatigue being a major component in both. Understanding the prevalence of ME in the post-acute phase of COVID illness can bring us a step closer to understanding its pathophysiology. In a multilingual country like ours, regionally translated criteria are a must for conducting large-scale surveys.}, } @article {pmid37355282, year = {2023}, author = {Pelosi, A}, title = {Disrespectful language about patients with long COVID.}, journal = {Lancet (London, England)}, volume = {401}, number = {10394}, pages = {2108}, pmid = {37355282}, issn = {1474-547X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Patients ; Professional-Patient Relations ; }, } @article {pmid37354724, year = {2023}, author = {Lin, CW and Wang, YH and Li, YE and Chiang, TY and Chiu, LW and Lin, HC and Chang, CT}, title = {COVID-related dysphonia and persistent long-COVID voice sequelae: A systematic review and meta-analysis.}, journal = {American journal of otolaryngology}, volume = {44}, number = {5}, pages = {103950}, pmid = {37354724}, issn = {1532-818X}, mesh = {Humans ; Male ; Female ; *Dysphonia/epidemiology/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; *Voice ; Voice Training ; }, abstract = {PURPOSE: Dysphonia is a common symptom due to the coronavirus disease of the 2019 (COVID-19) infection. Nonetheless, it is often underestimated for its impact on human's health. We conducted this first study to investigate the global prevalence of COVID-related dysphonia as well as related clinical factors during acute COVID-19 infection, and after a mid- to long-term follow-up following the recovery.

METHODS: Five electronic databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and Web of Science were systematically searched for relevant articles until Dec, 2022, and the reference of the enrolled studies were also reviewed. Dysphonia prevalence during and after COVID-19 infection, and voice-related clinical factors were analyzed; the random-effects model was adopted for meta-analysis. The one-study-removal method was used for sensitivity analysis. Publication bias was determined with funnel plots and Egger's tests.

RESULTS: Twenty-one articles comprising 13,948 patients were identified. The weighted prevalence of COVID-related dysphonia during infection was 25.1 % (95 % CI: 14.9 to 39.0 %), and male was significantly associated with lower dysphonia prevalence (coefficients: -0.116, 95 % CI: -0.196 to -0.036; P = .004) during this period. Besides, after recovery, the weighted prevalence of COVID-related dysphonia declined to 17.1 % (95 % CI: 11.0 to 25.8 %). 20.1 % (95 % CI: 8.6 to 40.2 %) of the total patients experienced long-COVID dysphonia.

CONCLUSIONS: A quarter of the COVID-19 patients, especially female, suffered from voice impairment during infection, and approximately 70 % of these dysphonic patients kept experiencing long-lasting voice sequelae, which should be noticed by global physicians.}, } @article {pmid37354471, year = {2023}, author = {Bhandari, S and Rankawat, G and Joshi, S and Tiwaskar, M and Lohmror, A and Bhandari, S}, title = {Post-COVID Syndrome: The Stranger Ghost of Culprit COVID-19.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {2}, pages = {11-12}, doi = {10.5005/japi-11001-0193}, pmid = {37354471}, issn = {0004-5772}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; }, abstract = {BACKGROUND: Post-COVID syndromes are the most abundant sequel of coronavirus disease of 2019 (COVID-19) infection, which affects millions of people around the whole world. There is a significant difference observed during the acute phase as well as during the post-COVID period between patients hospitalized with (alpha, delta, or omicron) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant. In the present scenario, when most people are vaccinated, COVID-19 disease is less likely, but the remnants of previous COVID-19 infections are still a vast health burden.

MATERIALS AND METHODS: This prospective, observational, comparative, and analytical study included a total of 3,840 COVID-19-infected patients who visited the hospital. We included 1,150 patients of alpha variants, 1,845 patients of delta variants, and 815 patients of omicron variants, from June 2020 to November 2020, March 2021 to July 2021, and January 2022 to May 2022, respectively. All medical data of the study population, including hospital stay and vaccination status, were collected, and all patients were followed up for 6 months of duration. All collected data were compiled and analyzed to compare the post-COVID thrombotic and other events among different variants of COVID-19.

RESULTS: Patients infected during the delta variant are the most symptomatic at onset (higher prevalence of fever, dyspnea, cough, myalgia, headache, or gastrointestinal problems) than those infected with the alpha or omicron variant (p < 0.01). A total of 2,830 patients (7.48%) [1,520 (82.38%) of delta variant, 598 (73.37%) of omicron variant, and 712 (60.34%) of omicron variant] developed post-COVID syndrome during their follow-up period out of 3,220 enrolled patients and the difference was statistically significant when compared among variants (p < 0.05). In this study, the highly prevalent post-COVID syndrome was mucormycosis (11.41%), followed by new-onset diabetes (9.89%), pulmonary fiosis (7.67%), ischemic heart disease (6.46%), ain stroke (3.29%), and other thromboembolic disorders (2.37%).

CONCLUSION: COVID-19-associated onset symptoms during the delta variant were more severe and highly prevalent, while neurological symptoms (aguesia and anosmia) were more common during the alpha variant. Patients infected with the delta variant of COVID-19 are more prone to develop post-COVID-associated complications with minimal risk in the omicron variant and intermediate risk in the alpha variant. Long COVID-19 requires specific attention for management, irrespective of the SARS-CoV-2 variant.}, } @article {pmid37352211, year = {2023}, author = {Horwitz, LI and Thaweethai, T and Brosnahan, SB and Cicek, MS and Fitzgerald, ML and Goldman, JD and Hess, R and Hodder, SL and Jacoby, VL and Jordan, MR and Krishnan, JA and Laiyemo, AO and Metz, TD and Nichols, L and Patzer, RE and Sekar, A and Singer, NG and Stiles, LE and Taylor, BS and Ahmed, S and Algren, HA and Anglin, K and Aponte-Soto, L and Ashktorab, H and Bassett, IV and Bedi, B and Bhadelia, N and Bime, C and Bind, MC and Black, LJ and Blomkalns, AL and Brim, H and Castro, M and Chan, J and Charney, AW and Chen, BK and Chen, LQ and Chen, P and Chestek, D and Chibnik, LB and Chow, DC and Chu, HY and Clifton, RG and Collins, S and Costantine, MM and Cribbs, SK and Deeks, SG and Dickinson, JD and Donohue, SE and Durstenfeld, MS and Emery, IF and Erlandson, KM and Facelli, JC and Farah-Abraham, R and Finn, AV and Fischer, MS and Flaherman, VJ and Fleurimont, J and Fonseca, V and Gallagher, EJ and Gander, JC and Gennaro, ML and Gibson, KS and Go, M and Goodman, SN and Granger, JP and Greenway, FL and Hafner, JW and Han, JE and Harkins, MS and Hauser, KSP and Heath, JR and Hernandez, CR and Ho, O and Hoffman, MK and Hoover, SE and Horowitz, CR and Hsu, H and Hsue, PY and Hughes, BL and Jagannathan, P and James, JA and John, J and Jolley, S and Judd, SE and Juskowich, JJ and Kanjilal, DG and Karlson, EW and Katz, SD and Kelly, JD and Kelly, SW and Kim, AY and Kirwan, JP and Knox, KS and Kumar, A and Lamendola-Essel, MF and Lanca, M and Lee-Lannotti, JK and Lefebvre, RC and Levy, BD and Lin, JY and Logarbo, BP and Logue, JK and Longo, MT and Luciano, CA and Lutrick, K and Malakooti, SK and Mallett, G and Maranga, G and Marathe, JG and Marconi, VC and Marshall, GD and Martin, CF and Martin, JN and May, HT and McComsey, GA and McDonald, D and Mendez-Figueroa, H and Miele, L and Mittleman, MA and Mohandas, S and Mouchati, C and Mullington, JM and Nadkarni, GN and Nahin, ER and Neuman, RB and Newman, LT and Nguyen, A and Nikolich, JZ and Ofotokun, I and Ogbogu, PU and Palatnik, A and Palomares, KTS and Parimon, T and Parry, S and Parthasarathy, S and Patterson, TF and Pearman, A and Peluso, MJ and Pemu, P and Pettker, CM and Plunkett, BA and Pogreba-Brown, K and Poppas, A and Porterfield, JZ and Quigley, JG and Quinn, DK and Raissy, H and Rebello, CJ and Reddy, UM and Reece, R and Reeder, HT and Rischard, FP and Rosas, JM and Rosen, CJ and Rouphael, NG and Rouse, DJ and Ruff, AM and Saint Jean, C and Sandoval, GJ and Santana, JL and Schlater, SM and Sciurba, FC and Selvaggi, C and Seshadri, S and Sesso, HD and Shah, DP and Shemesh, E and Sherif, ZA and Shinnick, DJ and Simhan, HN and Singh, U and Sowles, A and Subbian, V and Sun, J and Suthar, MS and Teunis, LJ and Thorp, JM and Ticotsky, A and Tita, ATN and Tragus, R and Tuttle, KR and Urdaneta, AE and Utz, PJ and VanWagoner, TM and Vasey, A and Vernon, SD and Vidal, C and Walker, T and Ward, HD and Warren, DE and Weeks, RM and Weiner, SJ and Weyer, JC and Wheeler, JL and Whiteheart, SW and Wiley, Z and Williams, NJ and Wisnivesky, JP and Wood, JC and Yee, LM and Young, NM and Zisis, SN and Foulkes, AS}, title = {Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0286297}, pmid = {37352211}, issn = {1932-6203}, support = {P30 AG072946/AG/NIA NIH HHS/United States ; UG1 HD027869/HD/NICHD NIH HHS/United States ; R00 AG065419/AG/NIA NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; UG1 HD087230/HD/NICHD NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; UG1 HD087192/HD/NICHD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; UG1 HD034208/HD/NICHD NIH HHS/United States ; P20 GM109089/GM/NIGMS NIH HHS/United States ; UG1 HD040544/HD/NICHD NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Adolescent ; Adult ; Multicenter Studies as Topic ; }, abstract = {IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.

METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.

DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

REGISTRATION: NCT05172024.}, } @article {pmid37352207, year = {2023}, author = {Romeiser, JL and Morley, CP and Singh, SM}, title = {COVID-19 symptom load as a risk factor for chronic pain: A national cross-sectional study.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0287554}, pmid = {37352207}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Cross-Sectional Studies ; *Chronic Pain/epidemiology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {INTRODUCTION: Emerging evidence suggests that a COVID-19 infection with a high initial severity may be associated with development of long-COVID conditions such as chronic pain. At the population level, it is unknown if severity of a COVID-19 infection might be a new risk factor for chronic pain above and beyond the traditional slate of pre-established risk factors. The purpose of this study is to examine whether COVID-19 severity of infection may be a new risk factor for chronic pain.

METHODS: Using data from the 2021 National Health Interview Survey (n = 15,335), this study examined the adjusted odds of experiencing high frequency levels of pain in the past 3 months for those who reported no/mild symptoms from a COVID-19 infection, and those reporting moderate/severe symptoms from COVID-19, compared to those never infected. A 1:1:1 propensity score matched analysis was also performed to examine the odds of pain.

RESULTS: Prevalence of pain was higher in the moderate/severe symptom group compared to the no infection group (25.48% vs 19.44%, p <0.001). Both the adjusted model (odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.09, 1.51) and matched model (OR = 1.45, CI = 1.14, 1.83) revealed higher odds of pain for those with moderate/high COVID-19 symptoms compared to no infection.

CONCLUSIONS: A moderate/highly symptomatic COVID-19 infection may be a new risk factor for chronic pain. As the absolute number of severe COVID-19 infections continues to rise, overall prevalence of chronic pain may also increase. While knowledge continues to unfold on long-haul symptoms, prevention of severe infections remains essential.}, } @article {pmid37351054, year = {2023}, author = {Najafi, MB and Javanmard, SH}, title = {Post-COVID-19 Syndrome Mechanisms, Prevention and Management.}, journal = {International journal of preventive medicine}, volume = {14}, number = {}, pages = {59}, pmid = {37351054}, issn = {2008-7802}, abstract = {As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.}, } @article {pmid37351002, year = {2023}, author = {Hovagemyan, F and Dugerdil, A and Braggion, A and Mallet, L and Flahault, A}, title = {Psychiatric consequences and issues of long COVID on patients with prior psychiatric comorbidities: a scoping review.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1181767}, pmid = {37351002}, issn = {1664-0640}, abstract = {SARS-CoV-2 is a growing field of research and mental health in long COVID is one of its interesting domains. This scoping review aims at studying the outcomes of mental health in patients already known for psychiatric illness. This was done by researching the literature in two databases (Embase and PubMed) for articles studying mental health consequences of long COVID in patients already known for psychiatric history. Eleven studies were included. 6/11 studies found an effect of long COVID, with varying severity of outcomes studied, with either a worsening in length or severity. 4/11 did not find any correlation between worsening symptoms and psychiatric history. The methods for assessing which psychiatric symptoms to include and how to determine prior history were heterogeneous, making direct comparison sometimes difficult. The data seem to show worse effects of long COVID on mental health of patients with prior mental illness, with limitations regarding the heterogeneity of the studies' designs and focuses. It also highlights how neglected this population of patients is in the current state of research.}, } @article {pmid37350206, year = {2023}, author = {El Moussaoui, M and Guiot, J and Frippiat, F and Darcis, G}, title = {[An emerging cause of chronic fatigue and pain : post-COVID-19 condition or long COVID].}, journal = {Revue medicale de Liege}, volume = {78}, number = {5-6}, pages = {299-304}, pmid = {37350206}, issn = {0370-629X}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; *COVID-19/complications ; SARS-CoV-2 ; Pain ; }, abstract = {Some individuals who have been infected with SARS-CoV-2 can experience long-term effects from their infection, known as post-COVID conditions, post-acute sequelae of COVID-19 or long COVID. Different underlying mechanisms can lead to long COVID, none of which are mutually exclusive. Lingering symptoms can persist years after SARS-CoV-2 infection, including fatigue, muscle weakness, tachycardia, dyspnea and various neurological symptoms. The symptomatology is partly similar to that reported by people with chronic fatigue syndrome and other unwell studied long-lasting diseases that may occur after other infections. People who have experienced more severe COVID-19 illness are at higher risk of developing long COVID, although anyone who was infected can experience post-COVID conditions. Importantly, unvaccinated individuals are more likely to develop long COVID. Here we review the current knowledge and discuss key findings regarding the epidemiology and physiopathology of long COVID. We briefly review current diagnostic and treatment options that remain so far largely insufficient.}, } @article {pmid37350170, year = {2023}, author = {Ha, EK and Kim, JH and Han, MY}, title = {Long COVID in children and adolescents: prevalence, clinical manifestations, and management strategies.}, journal = {Clinical and experimental pediatrics}, volume = {66}, number = {11}, pages = {465-474}, pmid = {37350170}, issn = {2713-4148}, abstract = {Long coronavirus disease (COVID), also known as postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection, has been defined as signs and symptoms which persist for 4 weeks or even lasting for 6 months after the initial infection. Although the prevalence of long COVID in children is currently unknown, epidemiological investigations have reported cases in pediatric populations. Clinical manifestations of long COVID in children include respiratory symptoms, such as cough and dyspnea, as well as neuropsychiatric and general conditions, including fatigue, headache, and muscle weakness. The pathophysiology of long COVID in children is still being investigated, but potential mechanisms include viral persistence, autoimmunity, and neuroinflammation. Risk factors for long COVID in children are not yet well understood, but studies have suggested that children with a history of severe acute COVID-19 infection or comorbidities may be at increased risk. Evaluation for respiratory symptoms of long COVID in children is essential, including spirometry and imaging studies to assess lung function and any potential damage. Furthermore, long COVID in children has been associated with a higher prevalence of mental health problems than in adults, emphasizing the importance of monitoring and addressing these aspects in pediatric patients. Although our understanding of long COVID in children and adolescents is still evolving, it is clear that the condition can have significant impacts on their health and well-being. The aim of this review is to synthesize the current knowledge on the prevalence, risk factors, and pathophysiology of long COVID in children and adolescents, and to discuss potential management strategies based on existing evidence.}, } @article {pmid37349962, year = {2023}, author = {Atiquzzaman, M and Thompson, JR and Shao, S and Djurdjev, O and Bevilacqua, M and Wong, MMY and Levin, A and Birks, PC}, title = {Long-term effect of COVID-19 infection on kidney function among COVID-19 patients followed in post-COVID-19 recovery clinics in British Columbia, Canada.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {38}, number = {12}, pages = {2816-2825}, doi = {10.1093/ndt/gfad121}, pmid = {37349962}, issn = {1460-2385}, mesh = {Humans ; Male ; Adolescent ; Adult ; Middle Aged ; Female ; Post-Acute COVID-19 Syndrome ; British Columbia/epidemiology ; COVID-19 Testing ; *Renal Insufficiency, Chronic/epidemiology ; *COVID-19/complications/epidemiology ; Glomerular Filtration Rate ; Kidney ; }, abstract = {BACKGROUND: We investigated the effect of Post-Acute COVID Syndrome or "long-COVID" on kidney function among patients followed in post-COVID recovery clinics (PCRC) in British Columbia, Canada.

METHODS: Long-COVID patients referred to PCRC between July 2020 to April 2022, aged ≥18 years who had an estimated glomerular filtration rate (eGFR) value recorded at 3 months from the coronavirus disease 2019 (COVID-19) diagnosis (index) date were included. Those requiring renal replacement therapy prior to index date were excluded. Primary outcome was change in eGFR and urine albumin-creatinine ratio (UACR) after COVID-19 infection. The proportion of patients in each of the six eGFR categories (<30, 30-44, 45-59, 60-89, 90-120 and >120 mL/min/1.73 m2) and three UACR categories (<3, 3-30 and >30 mg/mmol) in all of the study time points were calculated. Linear mixed model was used to investigate change in eGFR over time.

RESULTS: The study sample included 2212 long-COVID patients. Median age was 56 years, 51% were male. Half (∼47%-50%) of the study sample had normal eGFR (≥90 mL/min/1.73 m2) from COVID-19 diagnosis to 12 months post-COVID and <5% of patients had an eGFR <30 mL/min/1.73 m2. There was an estimated 2.96 mL/min/1.73 m2 decrease in eGFR within 1 year after COVID-19 infection that was equivalent to 3.39% reduction from the baseline. Decline in eGFR was highest in patients hospitalized for COVID-19 (6.72%) followed by diabetic patients (6.15%). More than 40% of patients were at risk of CKD.

CONCLUSIONS: People with long-COVID experienced a substantial decline in eGFR within 1 year from the infection date. The prevalence of proteinuria appeared to be high. Close monitoring of kidney function is prudent among patients with persistent COVID-19 symptoms.}, } @article {pmid37347585, year = {2023}, author = {Kamalakkannan, A and Sezgin, G and McLeod, A and Pearce, C and Georgiou, A and Prgomet, M and Weeding, S}, title = {Classification of Long COVID from General Practitioner Diagnosis Text.}, journal = {Studies in health technology and informatics}, volume = {304}, number = {}, pages = {124-125}, doi = {10.3233/SHTI230387}, pmid = {37347585}, issn = {1879-8365}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *General Practitioners ; *COVID-19/diagnosis ; Australia ; Records ; COVID-19 Testing ; }, abstract = {Major challenges exist in identifying Long COVID patients from diagnosis texts recorded by general practitioners. A classification framework is proposed that can be used to identify Long COVID patients given these unstructured diagnostic texts. This framework can be leveraged to provide a general understanding of the risk factors, management strategies, and outcomes associated with Long COVID in Australia.}, } @article {pmid37346808, year = {2023}, author = {Tang, J and Song, T and Kuang, M and Feng, Y and Liu, G and Liu, H}, title = {Recent Advancements on Long COVID in China: A Narrative Review.}, journal = {International journal of general medicine}, volume = {16}, number = {}, pages = {2585-2593}, pmid = {37346808}, issn = {1178-7074}, abstract = {The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.}, } @article {pmid37345771, year = {2023}, author = {}, title = {News Brief: Millions worldwide continue to suffer from post-COVID-19 condition (PCC), commonly known as long COVID.}, journal = {The American journal of nursing}, volume = {123}, number = {7}, pages = {14}, doi = {10.1097/01.NAJ.0000944888.25265.68}, pmid = {37345771}, issn = {1538-7488}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37345402, year = {2023}, author = {Sarıoğlu, N and Aksu, GD and Çoban, H and Bülbül, E and Demirpolat, G and Arslan, AT and Erel, F}, title = {[Response to "Clinical and radiological outcomes of long COVID and post-COVID fibrosis: Correspondence"].}, journal = {Tuberkuloz ve toraks}, volume = {71}, number = {2}, pages = {190-191}, pmid = {37345402}, issn = {2980-3187}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Radiography ; }, } @article {pmid37345401, year = {2023}, author = {Mungmunpuntipantip, R and Wiwanitkit, V}, title = {[Clinical and radiological outcomes of long COVID-19 and post-COVID fibrosis: Correspondence].}, journal = {Tuberkuloz ve toraks}, volume = {71}, number = {2}, pages = {188-189}, pmid = {37345401}, issn = {2980-3187}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Radiography ; }, } @article {pmid37344737, year = {2023}, author = {Sebők, S and Gyires, K}, title = {Long COVID and possible preventive options.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {2807-2817}, pmid = {37344737}, issn = {1568-5608}, mesh = {Humans ; Female ; Middle Aged ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Ritonavir ; }, abstract = {Most of the people who suffered from COVID-19 fully recovered, but approximately 10-20% of them developed a wide variety of symptoms after they recover from their initial illness. Long COVID can develop at any patient; however, several studies suggest that the development of Long Covid syndrome may be linked to severity of acute illness. Some of the risk factors are hospitalization (with mechanical ventilation), Intensive Care Unit admission, age (over 50 years), gender (female) and comorbidities. Since the precise mechanism of Long COVID has not been clarified, neither the management of Long COVID-19 syndrome has been solved yet. Promising results have been published with vaccines as they effectively reduced the risk of Long COVID; however, other data suggest that vaccination results only partial protection in the post-acute phase of the disease. Recently, the orally effective antiviral agents (Paxlovid, molnupiravir) are preferred for outpatient management, and they highly reduce the progression of mild-to-moderate COVID-19 to severe one, and consequently, might reduce the development of Long COVID. Finally, recently, several clinical trials are in progress with either dietary supplements or drugs with different mechanisms of action. Additional information on the precise mechanisms, risk factors of Long COVID may result in successful preventive and therapeutic management of Long Covid 19 syndrome.}, } @article {pmid37342998, year = {2023}, author = {De Domenico, M}, title = {Prevalence of long COVID decreases for increasing COVID-19 vaccine uptake.}, journal = {PLOS global public health}, volume = {3}, number = {6}, pages = {e0001917}, pmid = {37342998}, issn = {2767-3375}, abstract = {Long COVID is a post-COVID-19 condition characterized by persistent symptoms that can develop after SARS-CoV-2 infection. Estimating and comparing its prevalence across countries is difficult, hindering the quantitative assessment of massive vaccination campaigns as a preventive measure. By integrating epidemiological, demographic and vaccination data, we first reconcile the estimates of long COVID prevalence in the U.K. and the U.S., and estimate a 7-fold yearly increase in the global median prevalence between 2020 and 2022. Second, we estimate that vaccines against COVID-19 decrease the prevalence of long COVID among U.S. adults by 20.9% (95% CI: -32.0%, -9.9%) and, from the analysis of 158 countries, by -15.7% (95% CI: -18.0%, -13.4%) among all who had COVID-19. Our population-level analysis complements the current knowledge from patients data and highlights how aggregated data from fully operational epidemic surveillance and monitoring can inform about the potential impact of long COVID on national and global public health in the next future.}, } @article {pmid37342987, year = {2023}, author = {Sarri, G and Liu, W and Zabotka, L and Freitag, A and Claire, R and Wangge, G and Elvidge, J and Dawoud, D and Bennett, D and Wen, X and Li, X and Rentsch, CT and Uddin, MJ and Ali, MS and Gokhale, M and Déruaz-Luyet, A and Moga, DC and Guo, JJ and Zullo, AR and Patorno, E and Lin, KJ}, title = {Prognostic Factors of COVID-19: An Umbrella Review Endorsed by the International Society for Pharmacoepidemiology.}, journal = {Clinical pharmacology and therapeutics}, volume = {114}, number = {3}, pages = {604-613}, doi = {10.1002/cpt.2977}, pmid = {37342987}, issn = {1532-6535}, support = {R21 AG061632/AG/NIA NIH HHS/United States ; R03 AG070661/AG/NIA NIH HHS/United States ; R01 AG065722/AG/NIA NIH HHS/United States ; K01 AG073651/AG/NIA NIH HHS/United States ; R01 AG077620/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Male ; Female ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pharmacoepidemiology ; Prognosis ; Hospitalization ; }, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLRs) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings' interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022, which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.}, } @article {pmid37342500, year = {2023}, author = {Komaroff, AL and Lipkin, WI}, title = {ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1187163}, pmid = {37342500}, issn = {2296-858X}, support = {U54 AI138370/AI/NIAID NIH HHS/United States ; }, abstract = {Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.}, } @article {pmid37342246, year = {2023}, author = {Pruimboom, L}, title = {Editorial: Long COVID-19: ultimate reasoning as a need for the search of proximate solutions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1227626}, pmid = {37342246}, issn = {2235-2988}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid37340400, year = {2023}, author = {Al-Jabr, H and Hawke, LD and Thompson, DR and Clifton, A and Shenton, M and Castle, DJ and Ski, CF}, title = {Interventions to support mental health in people with long COVID: a scoping review.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1186}, pmid = {37340400}, issn = {1471-2458}, mesh = {Humans ; Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Mental Disorders/therapy/diagnosis ; Anxiety/therapy ; }, abstract = {INTRODUCTION: Long COVID (LC) is a multisystem disease with symptoms lasting weeks or months beyond the acute COVID-19 infection. Several manifestations are reported by people with LC, including effects on mental health, with varying degrees of psychological distress and disturbances to daily activities. Research conducted to identify effective interventions to support mental health among people with LC has been limited by the breadth and scope of studies.

AIM: This review aims to identify interventions being tested to support mental health of people with LC.

METHODS: A scoping review was conducted by searching five databases for articles published between January 2020 and early October 2022 to identify research evaluating interventions focused on improving mental health symptoms associated with LC. Results from all sources were checked for eligibility by two reviewers, and agreements were resolved by discussion. Gray literature and reference list of included studies and relevant reviews were scrutinised to identify any additional studies. Data extraction was conducted by one reviewer and checked by another reviewer for accuracy.

RESULTS: Of the 940 studies identified, 17 were included, the design of which varied but included mainly case studies (n = 6) and clinical trials (n = 5). Several interventions were described, ranging from single interventions (e.g., pharmacologic) to more holistic, comprehensive suites of services (pharmacologic and non-pharmacologic). Several mental health outcomes were measured, mostly anxiety and depression. All included studies were reported to be associated with improvements in participants' mental health outcomes.

CONCLUSION: This scoping review identified studies reporting on a variety of interventions to support mental health among people with LC. Although positive changes were reported by all studies, some were case studies and thus their findings must be interpreted with caution. There is a need for more research to be conducted to identify the impact of interventions on mental health of people with LC.}, } @article {pmid37337984, year = {2023}, author = {Cuschieri, S and Grech, S and Grech, V}, title = {A glimpse into Long COVID characteristics and the mental health impact within a highly vaccinated population: a Malta observational study.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {59}, number = {2}, pages = {101-107}, doi = {10.4415/ANN_23_02_02}, pmid = {37337984}, issn = {2384-8553}, mesh = {Adult ; Male ; Humans ; Female ; *COVID-19/epidemiology ; Mental Health ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Malta/epidemiology ; Anxiety/epidemiology ; }, abstract = {BACKGROUND: Post-acute COVID-19 consequences are gaining global recognition. This study explores Long COVID characteristics and associated mental health impact/s among the highly vaccinated adult population of Malta.

METHODS: A social media survey gathered demographics, vaccination, and COVID-19 data. Generalised Anxiety Disorder and Patient Health Questionnaire-9 assessment tools were used for anxiety and depression. Quantitative analyses were performed.

RESULTS: 41% reported Long COVID, mostly female, 30-39 years, absence of chronic disease/s and vaccinated. Shortness of breath commonest persistent symptom among males, and fatigue for females. Significantly higher depression scores were present in Long COVID cohort compared to no persistent symptoms (p=0.001) and never acquiring COVID-19 (p=<0.01). A significant higher anxiety scores was present for Long COVID cohort than never acquiring COVID-19 (p=<0.01).

CONCLUSIONS: Long COVID occurs even in healthy individuals and vaccinated, while exacerbating mental health burdens. Urgent action is required to manage Long COVID and preventing the sequela.}, } @article {pmid37337723, year = {2023}, author = {Rach, S and Kühne, L and Zeeb, H and Ahrens, W and Haug, U and Pohlabeln, H}, title = {Mild COVID-19 infection associated with post-COVID-19 condition after 3 months - a questionnaire survey.}, journal = {Annals of medicine}, volume = {55}, number = {1}, pages = {2226907}, pmid = {37337723}, issn = {1365-2060}, mesh = {Female ; Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; Pain ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19), caused by infection with SARS-CoV-2, can lead to post-COVID-19 condition, a secondary syndrome of persistent and new post-acute symptoms, but evidence on this syndrome is still scarce.

METHODS: In a questionnaire survey, residents of the city of Bremen (Germany) with verified SARS-CoV-2 infection were invited to answer questions (online questionnaire or interview) concerning symptoms experienced at the time of infection and at the time of questionnaire completion at least three months later. Main outcome of the analysis was the presence of a post-COVID-19 condition at the time of the interview, defined as the presence of at least two of three leading symptoms: fatigue, breathing difficulties, or cognitive problems.

RESULTS: A post-COVID-19 condition was more likely to be reported if respondents had, at the time of infection, suffered from fatigue (OR 1.75; 95% CI: 1.00, 3.06), breathing difficulties (OR 4.02; 95% CI: 2.80, 5.77), cognitive symptoms (OR 2.98; 95% CI: 1.48, 6.02), or head- & bone aches (OR 2.06; 95% CI: 1.25, 3.42). The odds of developing a post-COVID-19 condition increased with the number of symptoms at infection. Females were more likely to report a post-COVID-19 condition (OR 1.54; 95% CI: 1.05, 2.24). Analyzing only non-hospitalized respondents changed results only slightly.

CONCLUSION: Our study adds to growing evidence that even a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition. Females and those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to also experience post COVID-19 symptoms several months after infection.KEY MESSAGESEven a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition.Females seem more likely to develop a post-COVID-19 condition.Those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to develop a post-COVID-19 condition.}, } @article {pmid37336825, year = {2023}, author = {Mancilla-Corona, CO and Sanchez-Alavez, M and Pineda-García, G and Islas-Limon, JY and Zazueta, OE and Lopez-Baena, JV and Rodríguez-Vásquez, JI and Serafin-Higuera, IR}, title = {The influence of physical fatigue on telephone-based neuropsychological test performance in COVID-19 survivors.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {}, pmid = {37336825}, issn = {1433-8491}, abstract = {Fatigue has been characterized as a post COVID-19 condition known to persist months after SARS-CoV-2 infection. COVID-19 has been reported to be associated with impaired cognitive function, including disorders in attention, memory, information processing, and executive functions. The objective of this study was to determine if post-COVID fatigue, manifested as tiredness while performing low-intensity physical activity, has a detrimental effect on neuropsychological performance, to achieve this, we randomly selected 20 participants with post-COVID fatigue and 20 SARS-CoV-2 negative age-matched controls from a database of 360 residents of Tijuana, Baja California in a cross-sectional study design. All 40 participants responded to a health survey, along with a neuropsychological assessment test via telephone call. Statistical analysis was performed using a multiple linear regression model including the following independent variables: study condition (post-COVID fatigue or negative control), sex, age, years of education, hypertension, asthma, administration of supplemental oxygen during COVID-19 recovery, and the hour at which the evaluation started. Significant regression analysis was obtained for all global parameters of the assessment, including BANFE-2 score (p = 0.021, R[2] Adj. = 0.263), NEUROPSI score (p = 0.008, R[2] Adj. = 0.319), and total errors (p = 0.021, R[2] Adj. = 0.263), with significant regression coefficients for study condition on two global parameters, BANFE-2 score (p = 0.028, β = - 0.371) and NEUROPSI score (p = 0.010, β = -0.428). These findings suggest that the presence of post-COVID fatigue is a factor associated with a decrease in neuropsychological performance.}, } @article {pmid37336480, year = {2024}, author = {Al-Jewair, T and Michelogiannakis, D and Khoo, E and Prevost, R}, title = {Potential Impact of Long COVID-19 on Orthodontic Treatment.}, journal = {European journal of dentistry}, volume = {18}, number = {1}, pages = {387-391}, pmid = {37336480}, issn = {1305-7456}, abstract = {Pooled estimates indicate about 226 million individuals are currently experiencing or have experienced persistent symptoms from COVID-19. Long COVID-19 (LC) has been associated with a prolonged inflammatory and stress responses in affected individuals. Due to common pathways, LC could impact the biological mechanisms of orthodontic tooth movement, orthodontically-induced inflammatory root resorption and periodontal tissue response of patients undergoing orthodontic treatment. The authors of the present report discussed potential biological mechanisms through which LC may influence orthodontic treatment highlighting the need for further research in this area.}, } @article {pmid37335611, year = {2023}, author = {Fischer, A and Aguayo, GA and Oustric, P and Morin, L and Larche, J and Benoy, C and Fagherazzi, G}, title = {Co-Design of a Voice-Based Digital Health Solution to Monitor Persisting Symptoms Related to COVID-19 (UpcomingVoice Study): Protocol for a Mixed Methods Study.}, journal = {JMIR research protocols}, volume = {12}, number = {}, pages = {e46103}, pmid = {37335611}, issn = {1929-0748}, abstract = {BACKGROUND: Between 10% and 20% of people with a COVID-19 infection will develop the so-called long COVID syndrome, which is characterized by fluctuating symptoms. Long COVID has a high impact on the quality of life of affected people, who often feel abandoned by the health care system and are demanding new tools to help them manage their symptoms. New digital monitoring solutions could allow them to visualize the evolution of their symptoms and could be tools to communicate with health care professionals (HCPs). The use of voice and vocal biomarkers could facilitate the accurate and objective monitoring of persisting and fluctuating symptoms. However, to assess the needs and ensure acceptance of this innovative approach by its potential users-people with persisting COVID-19-related symptoms, with or without a long COVID diagnosis, and HCPs involved in long COVID care-it is crucial to include them in the entire development process.

OBJECTIVE: In the UpcomingVoice study, we aimed to define the most relevant aspects of daily life that people with long COVID would like to be improved, assess how the use of voice and vocal biomarkers could be a potential solution to help them, and determine the general specifications and specific items of a digital health solution to monitor long COVID symptoms using vocal biomarkers with its end users.

METHODS: UpcomingVoice is a cross-sectional mixed methods study and consists of a quantitative web-based survey followed by a qualitative phase based on semistructured individual interviews and focus groups. People with long COVID and HCPs in charge of patients with long COVID will be invited to participate in this fully web-based study. The quantitative data collected from the survey will be analyzed using descriptive statistics. Qualitative data from the individual interviews and the focus groups will be transcribed and analyzed using a thematic analysis approach.

RESULTS: The study was approved by the National Research Ethics Committee of Luxembourg (number 202208/04) in August 2022 and started in October 2022 with the launch of the web-based survey. Data collection will be completed in September 2023, and the results will be published in 2024.

CONCLUSIONS: This mixed methods study will identify the needs of people affected by long COVID in their daily lives and describe the main symptoms or problems that would need to be monitored and improved. We will determine how using voice and vocal biomarkers could meet these needs and codevelop a tailored voice-based digital health solution with its future end users. This project will contribute to improving the quality of life and care of people with long COVID. The potential transferability to other diseases will be explored, which will contribute to the deployment of vocal biomarkers in general.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05546918; https://clinicaltrials.gov/ct2/show/NCT05546918.

DERR1-10.2196/46103.}, } @article {pmid37334978, year = {2023}, author = {Luo, J and Zhang, J and Tang, HT and Wong, HK and Lyu, A and Cheung, CH and Bian, Z}, title = {Prevalence and risk factors of long COVID 6-12 months after infection with the Omicron variant among nonhospitalized patients in Hong Kong.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28862}, doi = {10.1002/jmv.28862}, pmid = {37334978}, issn = {1096-9071}, mesh = {Middle Aged ; Humans ; Female ; *Post-Acute COVID-19 Syndrome ; Hong Kong/epidemiology ; Prevalence ; *COVID-19/epidemiology ; BNT162 Vaccine ; Retrospective Studies ; SARS-CoV-2 ; Risk Factors ; Fatigue ; }, abstract = {Long COVID has been reported among patients with COVID-19, but little is known about the prevalence and risk factors associated with long COVID 6-12 months after infection with the Omicron variant. This is a large-scale retrospective study. A total of 6242 out of 12 950 nonhospitalized subjects of all ages with SARS-CoV-2 infection (confirmed by polymerase chain reaction/rapid antigen test) during the Omicron dominant outbreak (December 31, 2021-May 6, 2022) in Hong Kong were included. Prevalence of long COVID, frequencies of symptoms, and risk factors were analyzed. Three thousand four hundred and thirty (55.0%) subjects reported at least one long COVID symptom. The most reported symptom was fatigue (1241, 36.2%). Female gender, middle age, obesity, comorbidities, vaccination after infection, having more symptoms, and presenting fatigue/chest tightness/headache/diarrhea in the acute stage of illness were identified as associated risk factors for long COVID. Patients who had received three or more doses of vaccine were not associated with a lower risk of long COVID (adjusted odds ratio 1.105, 95% confidence interval 0.985-1.239, p = 0.088). Among patients with at least three doses of vaccine, there was no significant difference in the risk of long COVID between the CoronaVac vaccine and BNT162b2 vaccine (p > 0.05). Omicron infection can lead to long COVID in a significant proportion of nonhospitalized patients 6-12 months after infection. Further investigation is needed to uncover the mechanisms underlying the development of long COVID and determine the impact of various risk factors such as vaccines.}, } @article {pmid37334371, year = {2023}, author = {Bellucci, G and Albanese, A and Rizzi, C and Rinaldi, V and Salvetti, M and Ristori, G}, title = {The value of Interferon β in multiple sclerosis and novel opportunities for its anti-viral activity: a narrative literature review.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1161849}, pmid = {37334371}, issn = {1664-3224}, mesh = {Humans ; Interferon-beta/therapeutic use ; *Multiple Sclerosis/drug therapy ; *COVID-19 ; *Epstein-Barr Virus Infections/complications ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; Interferons/therapeutic use/pharmacology ; Antiviral Agents/therapeutic use/pharmacology ; }, abstract = {Interferon-beta (IFN-β) for Multiple Sclerosis (MS) is turning 30. The COVID-19 pandemic rejuvenated the interest in interferon biology in health and disease, opening translational opportunities beyond neuroinflammation. The antiviral properties of this molecule are in accord with the hypothesis of a viral etiology of MS, for which a credible culprit has been identified in the Epstein-Barr Virus. Likely, IFNs are crucial in the acute phase of SARS-CoV-2 infection, as demonstrated by inherited and acquired impairments of the interferon response that predispose to a severe COVID-19 course. Accordingly, IFN-β exerted protection against SARS-CoV-2 in people with MS (pwMS). In this viewpoint, we summarize the evidence on IFN-β mechanisms of action in MS with a focus on its antiviral properties, especially against EBV. We synopsize the role of IFNs in COVID-19 and the opportunities and challenges of IFN-β usage for this condition. Finally, we leverage the lessons learned in the pandemic to suggest a role of IFN-β in long-COVID-19 and in special MS subpopulations.}, } @article {pmid37333646, year = {2023}, author = {Paniskaki, K and Konik, MJ and Anft, M and Heidecke, H and Meister, TL and Pfaender, S and Krawczyk, A and Zettler, M and Jäger, J and Gaeckler, A and Dolff, S and Westhoff, TH and Rohn, H and Stervbo, U and Scheibenbogen, C and Witzke, O and Babel, N}, title = {Low avidity circulating SARS-CoV-2 reactive CD8+ T cells with proinflammatory TEMRA phenotype are associated with post-acute sequelae of COVID-19.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1196721}, pmid = {37333646}, issn = {1664-302X}, abstract = {The role of adaptive SARS-CoV-2 specific immunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although a growing population of convalescent COVID-19 patients with manifestation of PASC is observed. We analyzed the SARS-CoV-2-specific immune response, via pseudovirus neutralizing assay and multiparametric flow cytometry in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. Although frequencies of SARS-CoV-2-reactive CD4+ T cells were similar between the studied cohorts, a stronger SARS-CoV-2 reactive CD8+ T cell response, characterized by IFNγ production and predominant TEMRA phenotype but low functional TCR avidity was detected in PASC patients compared to controls. Of interest, high avidity SARS-CoV-2-reactive CD4+ and CD8+ T cells were comparable between the groups demonstrating sufficient cellular antiviral response in PASC. In line with the cellular immunity, neutralizing capacity in PASC patients was not inferior compared to controls. In conclusion, our data suggest that PASC may be driven by an inflammatory response triggered by an expanded population of low avidity SARS-CoV-2 reactive pro-inflammatory CD8+ T cells. These pro-inflammatory T cells with TEMRA phenotype are known to be activated by a low or even without TCR stimulation and lead to a tissue damage. Further studies including animal models are required for a better understanding of underlying immunopathogensis. Summary: A CD8+ driven persistent inflammatory response triggered by SARS-CoV-2 may be responsible for the observed sequelae in PASC patients.}, } @article {pmid37333619, year = {2023}, author = {Al-Hakeim, HK and Khairi Abed, A and Rouf Moustafa, S and Almulla, AF and Maes, M}, title = {Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID.}, journal = {Frontiers in molecular neuroscience}, volume = {16}, number = {}, pages = {1194769}, pmid = {37333619}, issn = {1662-5099}, abstract = {Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. In the present study, we measured serum TRY, TRYCATs, insulin resistance (using the Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection. We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, and IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, and IR (Long COVID), and PBT and SpO2 (acute COVID-19). In conclusion, the physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID, and lowered plasma tryptophan and increased kynurenine may contribute to these effects.}, } @article {pmid37333294, year = {2023}, author = {Ma, T and Suryawanshi, RK and Miller, SR and Ly, KK and Thomas, R and Elphick, N and Yin, K and Luo, X and Kaliss, N and Chen, IP and Montano, M and Sreekumar, B and Standker, L and Münch, J and Heath Damron, F and Palop, JJ and Ott, M and Roan, NR}, title = {Post-acute immunological and behavioral sequelae in mice after Omicron infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333294}, issn = {2692-8205}, support = {P30 DK063720/DK/NIDDK NIH HHS/United States ; F31 AI164671/AI/NIAID NIH HHS/United States ; P01 AG073082/AG/NIA NIH HHS/United States ; S10 OD018040/OD/NIH HHS/United States ; R01 AG062629/AG/NIA NIH HHS/United States ; RF1 AG062234/AG/NIA NIH HHS/United States ; }, abstract = {Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naïve mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.}, } @article {pmid37333243, year = {2023}, author = {Bramante, CT and Beckman, KB and Mehta, T and Karger, AB and Odde, DJ and Tignanelli, CJ and Buse, JB and Johnson, DM and Watson, RHB and Daniel, JJ and Liebovitz, DM and Nicklas, JM and Cohen, K and Puskarich, MA and Belani, HK and Siegel, LK and Klatt, NR and Anderson, B and Hartman, KM and Rao, V and Hagen, AA and Patel, B and Fenno, SL and Avula, N and Reddy, NV and Erickson, SM and Fricton, RD and Lee, S and Griffiths, G and Pullen, MF and Thompson, JL and Sherwood, N and Murray, TA and Rose, MR and Boulware, DR and Huling, JD}, title = {Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37333243}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; T32 HL129956/HL/NHLBI NIH HHS/United States ; P30 DK124723/DK/NIDDK NIH HHS/United States ; R21 LM012744/LM/NLM NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; R01 LM012982/LM/NLM NIH HHS/United States ; K23 HL133604/HL/NHLBI NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; }, abstract = {Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets.[1-3] Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy.[4] Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.[5] In vitro, metformin has antiviral activity against RNA viruses including SARS-CoV-2.[6,7] In the COVID-OUT phase 3, randomized, placebo-controlled trial of outpatient treatment of COVID-19, metformin had a 42% reduction in ER visits/hospitalizations/death through 14 days; a 58% reduction in hospitalizations/death through 28 days, and a 42% reduction in Long COVID through 10 months.[8,9] Here we show viral load analysis of specimens collected in the COVID-OUT trial that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95%CI, -1.05 to -0.06, p=0.027) while there was no virologic effect for ivermectin or fluvoxamine vs placebo. The metformin effect was consistent across subgroups and with emerging data.[10,11] Our results demonstrate, consistent with model predictions, that a safe, widely available,[12] well-tolerated, and inexpensive oral medication, metformin, can be repurposed to significantly reduce SARS-CoV-2 viral load.}, } @article {pmid37333163, year = {2023}, author = {Packard, SE and Susser, E}, title = {Association of Long COVID with housing insecurity in the United States, 2022-2023.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37333163}, support = {T32 MH013043/MH/NIMH NIH HHS/United States ; }, abstract = {OBJECTIVES: To assess the association of Long COVID with housing insecurity in the United States.

METHODS: To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don't report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative cross-sectional survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-today life were associated with a higher prevalence of housing insecurity.

RESULTS: During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity.

CONCLUSIONS: Compared with COVID-19 survivors who don't experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-today life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.}, } @article {pmid37330991, year = {2023}, author = {Rodseth, R and Maslo, C and Laubscher, A and Friedland, R}, title = {Readmission and inhospital death 1 year after COVID-19 hospitalization in South Africa.}, journal = {Journal of internal medicine}, volume = {294}, number = {3}, pages = {370-372}, doi = {10.1111/joim.13685}, pmid = {37330991}, issn = {1365-2796}, mesh = {Adult ; Humans ; *COVID-19 ; South Africa/epidemiology ; Pandemics ; Patient Readmission ; Hospitalization ; }, abstract = {BACKGROUND: Acute SARS-COVID-19 infection may increase readmission risk compared to other respiratory infections. We assessed the 1-year readmission and inhospital death rates of hospitalized SARS-COVID-19 patients compared to patients hospitalized with other types of pneumonia.

METHODS: We determined the 1-year readmission and inhospital death rate of adult patients initially hospitalized with a positive SARS-COVID-19 result, and subsequently discharged, between March 2020 and August 2021, at a Netcare private hospital in South Africa, and compared this to all hospitalized adult pneumonia patients in the 3 years prior to the COVID-19 pandemic (2017-2019).

RESULTS: The 1-year readmission rate in COVID-19 patients was 6.6% (328/50,067) versus 8.5% in pneumonia patients (4699/55,439; p < 0.001), with an inhospital mortality rate of 7.7% (n = 251) and 9.7% (n = 454; p = 0.002) for COVID-19 and pneumonia patients, respectively.}, } @article {pmid37330479, year = {2023}, author = {Sedik, RNM}, title = {The clinical course and outcomes of SARS-CoV-2 virus infection in children: a 24-week follow-up study in Sulaimaniyah, Iraq.}, journal = {BMC pediatrics}, volume = {23}, number = {1}, pages = {303}, pmid = {37330479}, issn = {1471-2431}, mesh = {Child ; Humans ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; Iraq/epidemiology ; Prospective Studies ; Disease Progression ; }, abstract = {Most children infected with the SARS-CoV-2 virus have asymptomatic or mild disease with a short clinical course and excellent outcome; meanwhile, some children experienced persisting symptoms lasting > 12 weeks from the COVID-19 infection diagnosis. This study aimed to define the acute clinical course of SARS-CoV-2 virus infection and outcomes in children after recovery. This prospective cohort study was conducted on 105 children (aged < 16 years) with confirmed COVID-19 infection at Jamal Ahmed Rashid Teaching Hospital, Sulaimaniyah, Iraq, from July to September 2021. The symptomatic and suspicious cases of COVID-19 infection in children were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. About 85.6% of children fully recovered at ≤ 4 weeks from initial COVID-19 infection diagnosis, 42% were hospitalized, while 15.2% reported long COVID-19 infection symptoms. The most commonly reported symptoms were fatigue (7.1%), hair fall (4.0%), lack of concentration (3.0%), and abdominal pain (2.0%). Children aged 11-16 showed a greater risk of long-term COVID-19 infection symptoms. We also observed a higher risk of long COVID infection symptoms in those who reported ongoing symptoms at 4-6 weeks of follow-up assessment (p = 0.01). Despite mild disease and complete recovery in most children, many suffered from long COVID infection symptoms.}, } @article {pmid37330018, year = {2023}, author = {Guardino, ET and Tarko, L and Wilson, PWF and Gaziano, JM and Cho, K and Gagnon, DR and Orkaby, AR}, title = {Predictive value of ASCVD risk score for mortality and major adverse cardiovascular events in the year following a COVID-19 infection among US Veterans.}, journal = {International journal of cardiology}, volume = {387}, number = {}, pages = {131120}, pmid = {37330018}, issn = {1874-1754}, support = {I01 CX001025/CX/CSRD VA/United States ; }, mesh = {Humans ; Male ; Middle Aged ; Female ; Retrospective Studies ; *Veterans ; Risk Assessment ; *COVID-19 ; *Atherosclerosis ; Risk Factors ; *Cardiovascular Diseases/diagnosis ; }, abstract = {BACKGROUND: Morbidity and mortality following COVID-19 infection may be influenced by baseline atherosclerotic cardiovascular disease (ASCVD) risk, yet limited data are available to identify those at highest risk. We examined the association between baseline ASCVD risk with mortality and major adverse cardiovascular events (MACE) in the year following COVID-19 infection.

METHODS: We evaluated a nationwide retrospective cohort of US Veterans free of ASCVD who were tested for COVID-19. The primary outcome was absolute risk of all-cause mortality in the year following a COVID-19 test among those hospitalized vs. not stratified by baseline VA-ASCVD risk scores. Secondarily, risk of MACE was examined.

RESULTS: There were 393,683 Veterans tested for COVID-19 and 72,840 tested positive. Mean age was 57 years, 86% were male, and 68% were white. Within 30 days following infection, hospitalized Veterans with VA-ASCVD scores >20% had an absolute risk of death of 24.6% vs. 9.7% (P ≤0.0001) for those who tested positive and negative for COVID-19 respectively. In the year following infection, risk of mortality attenuated with no difference in risk after 60 days. The absolute risk of MACE was similar for Veterans who tested positive or negative for COVID-19.

CONCLUSIONS: Veterans without clinical ASCVD experienced an increased absolute risk of death within 30 days of a COVID-19 infection compared to Veterans with the same VA-ASCVD risk score who tested negative, but this risk attenuated after 60 days. Whether cardiovascular preventive medications can lower the risk of mortality and MACE in the acute period following COVID-19 infection should be evaluated.}, } @article {pmid37328773, year = {2023}, author = {Wang, C and Ramasamy, A and Verduzco-Gutierrez, M and Brode, WM and Melamed, E}, title = {Acute and post-acute sequelae of SARS-CoV-2 infection: a review of risk factors and social determinants.}, journal = {Virology journal}, volume = {20}, number = {1}, pages = {124}, pmid = {37328773}, issn = {1743-422X}, support = {NIAAA K08 T26-1616-11/NH/NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; Post-Acute COVID-19 Syndrome ; *Epstein-Barr Virus Infections ; Social Determinants of Health ; *COVID-19/complications ; Herpesvirus 4, Human ; SARS-CoV-2 ; Risk Factors ; Disease Progression ; }, abstract = {SARS-CoV-2 infection leading to Coronavirus Disease 2019 (COVID-19) has caused more than 762 million infections worldwide, with 10-30% of patients suffering from post-acute sequelae of SARS-CoV-2 infections (PASC). Initially thought to primarily affect the respiratory system, it is now known that SARS-CoV-2 infection and PASC can cause dysfunction in multiple organs, both during the acute and chronic stages of infection. There are also multiple risk factors that may predispose patients to worse outcomes from acute SARS-CoV-2 infection and contribute to PASC, including genetics, sex differences, age, reactivation of chronic viruses such as Epstein Barr Virus (EBV), gut microbiome dysbiosis, and behavioral and lifestyle factors, including patients' diet, alcohol use, smoking, exercise, and sleep patterns. In addition, there are important social determinants of health, such as race and ethnicity, barriers to health equity, differential cultural perspectives and biases that influence patients' access to health services and disease outcomes from acute COVID-19 and PASC. Here, we review risk factors in acute SARS-CoV-2 infection and PASC and highlight social determinants of health and their impact on patients affected with acute and chronic sequelae of COVID-19.}, } @article {pmid37328761, year = {2023}, author = {Bergantini, L and Baldassarri, M and d'Alessandro, M and Brunelli, G and Fabbri, G and Zguro, K and Degl'Innocenti, A and , and Fallerini, C and Bargagli, E and Renieri, A}, title = {Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder.}, journal = {Respiratory research}, volume = {24}, number = {1}, pages = {158}, pmid = {37328761}, issn = {1465-993X}, support = {Bando Ricerca COVID-19 Toscana//Azienda Ospedaliero-Universitaria Senese/ ; N B/2020/0119 "Identificazione delle basi genetiche determinanti la variabilità clinica della risposta a COVID-19 nella popolazione italiana//Intesa San Paolo 2020 charity fund/ ; Bando FISR 2020 "Editing dell'RNA contro il SARS-CoV-2: hackerare il virus per identificare bersagli molecolari e attenuare l'infezione - HACKTHECOV"//Italian Ministry of University and Research/ ; "PAT-COVID: Host genetics and pathogenetic mechanisms of COVID-19" (ID n. 2020-2016_RIC_3)//Istituto Buddista Italiano Soka Gakkai/ ; International consortium for integrative genomics prediction (INTERVENE) Grant Agreement No. 101016775//EU project H2020-SC1-FA-DTS-2018-2020/ ; }, mesh = {Humans ; *COVID-19/diagnosis/genetics ; *DNA Helicases/genetics ; Lung ; *Post-Acute COVID-19 Syndrome/genetics ; *Pulmonary Fibrosis/diagnosis/genetics ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized.

METHODS: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases.

RESULTS: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis.

CONCLUSION: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 (www.

CLINICALTRIAL: org).}, } @article {pmid37328666, year = {2023}, author = {Murugan, AK and Alzahrani, AS}, title = {Potential impacts of SARS-CoV-2 on parathyroid: current advances and trends.}, journal = {Endocrine}, volume = {81}, number = {3}, pages = {391-408}, pmid = {37328666}, issn = {1559-0100}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Furin/metabolism ; COVID-19 Vaccines ; Parathyroid Glands/metabolism ; Angiotensin-Converting Enzyme 2 ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A ; }, abstract = {Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection affects several important organs including endocrine glands. Experimental studies demonstrated that the virus exploits the ACE2, a transmembrane glycoprotein on the cell surface as a receptor for cellular entry. This entry process is exclusively facilitated by other intracellular protein molecules such as TMPRSS2, furin, NRP1, and NRP2. Recent findings documented the involvement of the SARS-CoV-2 in inducing various parathyroid disorders including hypoparathyroidism and hypocalcemia, which received significant attention. This review extensively describes rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various parathyroid disorders due to SARS-CoV-2 infection particularly parathyroid malfunction in COVID-19 cases, and post-COVID-19 conditions. Further, it presents the expression level of various molecules such as ACE2, TMPRSS2, furin, NRP1, and NRP2 in the parathyroid cells that facilitate the SARS-CoV-2 entry into the cell, and discusses the possible mechanism of parathyroid gland infection. Besides, it explores parathyroid malfunction in COVID-19 vaccine-administered cases. It also explains the possible long-COVID-19 effect on parathyroid and post-COVID-19 management of parathyroid. A complete understanding of the mechanisms of SARS-CoV-2-triggered pathogenesis in parathyroid dysfunctions may curtail treatment options and aid in the management of SARS-CoV-2-infected cases.}, } @article {pmid37326700, year = {2024}, author = {Gloeckl, R and Leitl, D and Schneeberger, T and Jarosch, I and Koczulla, AR}, title = {Rehabilitative interventions in patients with persistent post COVID-19 symptoms-a review of recent advances and future perspectives.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1819-1828}, pmid = {37326700}, issn = {1433-8491}, mesh = {Humans ; *COVID-19/rehabilitation ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has not only caused millions of deaths but left also millions of people with persistent symptoms behind. These long-term COVID-19 sequelae cause a considerable burden on individuals´ health, healthcare systems, and economies worldwide given the high rate of SARS-CoV-2 infections. Therefore, rehabilitative interventions and strategies are needed to counteract the post COVID-19 sequelae. The importance of rehabilitation for patients with persistent COVID-19 symptoms has been recently also highlighted in a Call for Action by the World Health Organisation. Based on previously published research, but also in line with clinical experience, COVID-19 is not one specific disease but rather presents in different phenotypes that vary in their pathophysiological mechanisms, symptomatic manifestations, and potential interventional approaches. This review provides a proposal for differentiating post COVID-19 patients in non-organ-specific phenotypes that may help clinicians to evaluate patients and to plan therapeutic options. Furthermore, we present current unmet needs and suggest a potential pathway for a specific rehabilitation approach in people with persistent post-COVID symptoms.}, } @article {pmid37325147, year = {2023}, author = {Dong, T and Wang, M and Liu, J and Ma, P and Pang, S and Liu, W and Liu, A}, title = {Diagnostics and analysis of SARS-CoV-2: current status, recent advances, challenges and perspectives.}, journal = {Chemical science}, volume = {14}, number = {23}, pages = {6149-6206}, pmid = {37325147}, issn = {2041-6520}, abstract = {The disastrous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced severe public healthcare issues and weakened the global economy significantly. Although SARS-CoV-2 infection is not as fatal as the initial outbreak, many infected victims suffer from long COVID. Therefore, rapid and large-scale testing is critical in managing patients and alleviating its transmission. Herein, we review the recent advances in techniques to detect SARS-CoV-2. The sensing principles are detailed together with their application domains and analytical performances. In addition, the advantages and limits of each method are discussed and analyzed. Besides molecular diagnostics and antigen and antibody tests, we also review neutralizing antibodies and emerging SARS-CoV-2 variants. Further, the characteristics of the mutational locations in the different variants with epidemiological features are summarized. Finally, the challenges and possible strategies are prospected to develop new assays to meet different diagnostic needs. Thus, this comprehensive and systematic review of SARS-CoV-2 detection technologies may provide insightful guidance and direction for developing tools for the diagnosis and analysis of SARS-CoV-2 to support public healthcare and effective long-term pandemic management and control.}, } @article {pmid37324463, year = {2023}, author = {Fiedler, L and Motloch, LJ and Dieplinger, AM and Jirak, P and Davtyan, P and Gareeva, D and Badykova, E and Badykov, M and Lakman, I and Agapitov, A and Sadikova, L and Pavlov, V and Föttinger, F and Mirna, M and Kopp, K and Hoppe, UC and Pistulli, R and Cai, B and Yang, B and Zagidullin, N}, title = {Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1093396}, pmid = {37324463}, issn = {1663-9812}, abstract = {Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ [2]-statistics = 6.45, p = 0.013 and SCD: χ [2]-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.}, } @article {pmid37324057, year = {2023}, author = {Moyers, SA and Hartwell, M and Chiaf, A and Greiner, B and Oliver, JA and Croff, JM}, title = {Associations of Combustible Cigarette, Electronic Cigarette, and Dual Use With COVID Infection and Severity in the U.S.: A Cross-sectional Analysis of the 2021 National Health Information Survey.}, journal = {Tobacco use insights}, volume = {16}, number = {}, pages = {1179173X231179675}, pmid = {37324057}, issn = {1179-173X}, support = {K23 DA042898/DA/NIDA NIH HHS/United States ; P20 GM109097/GM/NIGMS NIH HHS/United States ; U01 DA055349/DA/NIDA NIH HHS/United States ; }, abstract = {Given the potential respiratory health risks, the association of COVID infection and the use of combustible cigarettes, electronic nicotine delivery systems (ENDS), and concurrent dual use is a priority for public health. Many published reports have not accounted for known covarying factors. This study sought to calculate adjusted odds ratios for self-reported COVID infection and disease severity as a function of smoking and ENDS use, while accounting for factors known to influence COVID infection and disease severity (i.e., age, sex, race and ethnicity, socioeconomic status and educational attainment, rural or urban environment, self-reported diabetes, COPD, coronary heart disease, and obesity status). Data from the 2021 U.S. National Health Interview Survey, a cross-sectional questionnaire design, were used to calculate both unadjusted and adjusted odds ratios for self-reported COVID infection and severity of symptoms. Results indicate that combustible cigarette use is associated with a lower likelihood of self-reported COVID infection relative to non-use of tobacco products (AOR = .64; 95% CI [.55, .74]), whereas ENDS use is associated with a higher likelihood of self-reported COVID infection (AOR = 1.30; 95% CI [1.04, 1.63]). There was no significant difference in COVID infection among dual users (ENDS and combustible use) when compared with non-users. Adjusting for covarying factors did not substantially change the results. There were no significant differences in COVID disease severity between those of varying smoking status. Future research should examine the relationship between smoking status and COVID infection and disease severity utilizing longitudinal study designs and non-self-report measures of smoking status (e.g., the biomarker cotinine), COVID infection (e.g., positive tests), and disease severity (e.g., hospitalizations, ventilator assistance, mortality, and ongoing symptoms of long COVID).}, } @article {pmid37323930, year = {2023}, author = {Kim, M and Sim, S and Yang, J and Kim, M}, title = {Multivariate prediction of long COVID headache in adolescents using gray matter structural MRI features.}, journal = {Frontiers in human neuroscience}, volume = {17}, number = {}, pages = {1202103}, pmid = {37323930}, issn = {1662-5161}, abstract = {OBJECTIVE: Headache is among the most frequent symptoms after coronavirus disease 2019 (COVID-19), so-called long COVID syndrome. Although distinct brain changes have been reported in patients with long COVID, such reported brain changes have not been used for predictions and interpretations in a multivariate manner. In this study, we applied machine learning to assess whether individual adolescents with long COVID can be accurately distinguished from those with primary headaches.

METHODS: Twenty-three adolescents with long COVID headaches with the persistence of headache for at least 3 months and 23 age- and sex-matched adolescents with primary headaches (migraine, new daily persistent headache, and tension-type headache) were enrolled. Multivoxel pattern analysis (MVPA) was applied for disorder-specific predictions of headache etiology based on individual brain structural MRI. In addition, connectome-based predictive modeling (CPM) was also performed using a structural covariance network.

RESULTS: MVPA correctly classified long COVID patients from primary headache patients, with an area under the curve of 0.73 (accuracy = 63.4%; permutation p = 0.001). The discriminating GM patterns exhibited lower classification weights for long COVID in the orbitofrontal and medial temporal lobes. The CPM using the structural covariance network achieved an area under the curve of 0.81 (accuracy = 69.5%; permutation p = 0.005). The edges that classified long COVID patients from primary headache were mainly comprising thalamic connections.

CONCLUSION: The results suggest the potential value of structural MRI-based features for classifying long COVID headaches from primary headaches. The identified features suggest that the distinct gray matter changes in the orbitofrontal and medial temporal lobes occurring after COVID, as well as altered thalamic connectivity, are predictive of headache etiology.}, } @article {pmid37322633, year = {2023}, author = {Dhooria, S and Arora, S and Chaudhary, S and Sehgal, IS and Prabhakar, N and Mohammad, N and Sharma, R and Das, P and Kumar, Y and Garg, M and Puri, GD and Bhalla, A and Muthu, V and Prasad, KT and Agarwal, R and Aggarwal, AN}, title = {Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.}, journal = {The Indian journal of medical research}, volume = {157}, number = {5}, pages = {427-437}, pmid = {37322633}, issn = {0975-9174}, mesh = {Adult ; Humans ; *COVID-19 ; SARS-CoV-2 ; Risk Factors ; Biomarkers ; Lung/diagnostic imaging ; Transforming Growth Factor beta ; Retrospective Studies ; }, abstract = {BACKGROUND & OBJECTIVES: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA.

METHODS: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-β (TGF-β) were also compared among cases, controls and healthy volunteers.

RESULTS: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-β levels than healthy volunteers.

Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-β should be evaluated further as a biomarker.}, } @article {pmid37322387, year = {2023}, author = {Gremme, Y and Derlien, S and Katzer, K and Reuken, PA and Stallmach, A and Lewejohann, JC and Lemhöfer, C}, title = {Visualizing exertional dyspnea in a post-COVID patient using electrical impedance tomography.}, journal = {Infection}, volume = {51}, number = {6}, pages = {1841-1845}, pmid = {37322387}, issn = {1439-0973}, mesh = {Humans ; Electric Impedance ; *COVID-19/complications ; Tomography, X-Ray Computed ; Lung/diagnostic imaging ; Dyspnea/diagnosis/etiology ; }, abstract = {PURPOSE AND METHOD: Many post-COVID patients suffer from dyspnea on exertion. To visualize exercise-induced dyspnea, a post-COVID patient and a healthy volunteer underwent an exercise test on a treadmill under stress relevant to everyday life monitored by electrical impedance tomography (EIT).

RESULTS: The lung-healthy volunteer showed an even ventilation distribution throughout the assessment, a large ventilated area, and a butterfly-like lung shape with a convex lung rim. The post-COVID patient showed clear differences in the ventilated area compared to the control subject. During exercise, a constantly changing picture of differently ventilated areas is shown. However, especially the anterior regions were under-ventilated and larger areas were partially absent from ventilation. Overall, uncoordinated breathing and an uneven distribution of ventilation dominated the findings.

CONCLUSION: EIT is suitable for visualizing disturbed ventilation of the lungs, both at rest and under stress. The potential as a diagnostic tool in dyspnea assessment should be investigated.}, } @article {pmid37320945, year = {2023}, author = {Feter, N and Caputo, EL and Delpino, FM and Leite, JS and da Silva, LS and de Almeida Paz, I and Santos Rocha, JQ and Vieira, YP and Schröeder, N and da Silva, CN and Baptista Gonçalves, JC and da Costa Pereira, H and Barbosa, TA and Cassuriaga, J and da Silva, MC and Reichert, FF and Rombaldi, AJ}, title = {Physical activity and long COVID: findings from the Prospective Study About Mental and Physical Health in Adults cohort.}, journal = {Public health}, volume = {220}, number = {}, pages = {148-154}, pmid = {37320945}, issn = {1476-5616}, mesh = {Humans ; Adult ; Female ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prospective Studies ; Retrospective Studies ; Exercise ; }, abstract = {OBJECTIVES: The study investigated the longitudinal association between physical activity and the risk of long COVID in patients who recovered from COVID-19 infection.

STUDY DESIGN: We analyzed longitudinal data of the Prospective Study About Mental and Physical Health cohort, a prospective cohort study with adults living in Southern Brazil.

METHODS: Participants responded to an online, self-administered questionnaire in June 2020 (wave 1) and June 2022 (wave 4). Only participants who self-reported a positive test for COVID-19 were included. Physical activity was assessed before (wave 1, retrospectively) and during the pandemic (wave 1). Long COVID was assessed in wave 4 and defined as any post-COVID-19 symptoms that persisted for at least 3 months after infection.

RESULTS: A total of 237 participants (75.1% women; mean age [standard deviation]: 37.1 [12.3]) were included in this study. The prevalence of physical inactivity in baseline was 71.7%, whereas 76.4% were classified with long COVID in wave 4. In the multivariate analysis, physical activity during the pandemic was associated with a reduced likelihood of long COVID (prevalence ratio [PR]: 0.83; 95% confidence interval [CI]: 0.69-0.99) and a reduced duration of long COVID symptoms (odds ratio: 0.44; 95% CI: 0.26-0.75). Participants who remained physically active from before to during the pandemic were less likely to report long COVID (PR: 0.74; 95% CI: 0.58-0.95), fatigue (PR: 0.49; 95% CI: 0.32-0.76), neurological complications (PR: 0.47; 95% CI: 0.27-0.80), cough (PR: 0.40; 95% CI: 0.22-0.71), and loss of sense of smell or taste (PR: 0.43; 95% CI: 0.21-0.87) as symptom-specific long COVID.

CONCLUSION: Physical activity practice was associated with reduced risk of long COVID in adults.}, } @article {pmid37317282, year = {2023}, author = {Halma, MTJ and Plothe, C and Marik, P and Lawrie, TA}, title = {Strategies for the Management of Spike Protein-Related Pathology.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317282}, issn = {2076-2607}, abstract = {In the wake of the COVID-19 crisis, a need has arisen to prevent and treat two related conditions, COVID-19 vaccine injury and long COVID-19, both of which can trace at least part of their aetiology to the spike protein, which can cause harm through several mechanisms. One significant mechanism of harm is vascular, and it is mediated by the spike protein, a common element of the COVID-19 illness, and it is related to receiving a COVID-19 vaccine. Given the significant number of people experiencing these two related conditions, it is imperative to develop treatment protocols, as well as to consider the diversity of people experiencing long COVID-19 and vaccine injury. This review summarizes the known treatment options for long COVID-19 and vaccine injury, their mechanisms, and their evidentiary basis.}, } @article {pmid37316880, year = {2023}, author = {Gandjour, A}, title = {Long COVID: Costs for the German economy and health care and pension system.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {641}, pmid = {37316880}, issn = {1472-6963}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; SARS-CoV-2 ; Health Expenditures ; Pensions ; }, abstract = {BACKGROUND: Patients with acute COVID-19 can develop persistent symptoms (long/post COVID-19 syndrome). This study aimed to project the economic, health care, and pension costs due to long/post-COVID-19 syndrome with new onset in Germany in 2021.

METHODS: Using secondary data, economic costs were calculated based on wage rates and the loss of gross value-added. Pension payments were determined based on the incidence, duration, and amount of disability pensions. Health care expenditure was calculated based on rehabilitation expenses.

RESULTS: The analysis estimated a production loss of 3.4 billion euros. The gross value-added loss was calculated to be 5.7 billion euros. The estimated financial burden on the health care and pension systems due to SARS-CoV-2 infection was approximately 1.7 billion euros. Approximately 0.4 percent of employees are projected to be wholly or partially withdrawn from the labor market in the medium term due to long/post-COVID with new onset in 2021.

CONCLUSION: Costs of long/post-COVID-19 syndrome with new onset in 2021 are not negligible for the German economy and health care and pension systems but may still be manageable.}, } @article {pmid37316403, year = {2023}, author = {Golan, H and Courtney, R and Wolfberg, J}, title = {Novel Respiratory Therapy for the Improvement of Post COVID Condition Symptoms: A Case Series.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jvoice.2023.04.024}, pmid = {37316403}, issn = {1873-4588}, abstract = {INTRODUCTION: Speech-language pathologists are seeing a growing number of patients whose voice and upper airway symptoms are complicated by dyspnea, cognitive difficulties, anxiety, extreme fatigue, and other debilitating post COVID symptoms. These patients are often less responsive to traditional speech-language pathology treatments and there is emerging literature that suggests dysfunctional breathing (DB) might contribute to dyspnea and other symptoms in this patient population. Treatment of DB through breathing retraining has been shown to improve breathing and successfully reduce symptoms similar to those seen in patients with long COVID. There is some preliminary evidence that breathing retraining is helpful for patients with post COVID condition symptoms. However, breathing retraining protocols tend to be heterogeneous and are often not systematic or well described.

METHODS: This case series reports on an Integrative Breathing Therapy (IBT) protocol used in patients diagnosed with post COVID condition symptoms attending an otolaryngology clinic who presented with signs and symptoms of DB. A systematic evaluation of the biomechanical, biochemical, and psychophysiological dimensions of DB based on principles of IBT was performed on each patient to enable targeted patient-centered care. Patients were then provided with intensive breathing retraining that aimed to comprehensively improve breathing functionality in all these three dimensions of breathing. Treatment involved 6-12 sessions of weekly 1-hour group telehealth sessions combined with 2-4 individual sessions.

RESULTS: All participants showed improvements in the parameters of DB measured and also reported a reduction in symptoms and improved daily function.

CONCLUSIONS: These findings suggest that patients with long COVID who present with signs and symptoms of DB might respond positively to comprehensive and intensive breathing retraining that addresses biochemical, biomechanical, and psychophysiological dimensions of breathing. More research is required to further refine this protocol and confirm its effectiveness through a controlled trial.}, } @article {pmid37316184, year = {2023}, author = {Tabor, JB and Brett, BL and Nelson, L and Meier, T and Penner, LC and Mayer, AR and Echemendia, RJ and McAllister, T and Meehan, WP and Patricios, J and Makdissi, M and Bressan, S and Davis, GA and Premji, Z and Schneider, KJ and Zetterberg, H and McCrea, M}, title = {Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review.}, journal = {British journal of sports medicine}, volume = {57}, number = {12}, pages = {789-797}, doi = {10.1136/bjsports-2022-106680}, pmid = {37316184}, issn = {1473-0480}, mesh = {Humans ; *Brain Concussion/diagnosis ; Biomarkers ; Data Collection ; Databases, Factual ; Genetic Testing ; }, abstract = {OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC).

DESIGN: Systematic review.

DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study.

Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants.

RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research.

CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice.

PROSPERO REGISTRATION NUMBER: CRD42020164558.}, } @article {pmid37315957, year = {2023}, author = {Evans, R and Pick, A and Lardner, R and Masey, V and Smith, N and Greenhalgh, T}, title = {Breathing difficulties after covid-19: a guide for primary care.}, journal = {BMJ (Clinical research ed.)}, volume = {381}, number = {}, pages = {e074937}, doi = {10.1136/bmj-2023-074937}, pmid = {37315957}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; Dyspnea ; Primary Health Care ; }, } @article {pmid37315513, year = {2023}, author = {Antar, AAR and Peluso, MJ}, title = {CROI 2023: Acute and Post-Acute COVID-19.}, journal = {Topics in antiviral medicine}, volume = {31}, number = {3}, pages = {493-509}, pmid = {37315513}, issn = {2161-5853}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use ; *Retroviridae Infections ; }, abstract = {Studies of acute and post-acute COVID-19 were presented at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI). Early treatment with ensitrelvir, a novel protease inhibitor, hastened viral clearance and symptom resolution during coronavirus disease 2019 (COVID-19) and appeared to reduce the prevalence of long COVID symptoms. The development of novel agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including those with broader sarbecovirus activity such as anti-angiotensin-converting enzyme 2 monoclonal antibodies, is underway. A growing understanding of the pathophysiology of long COVID has provided several potential therapeutic targets for individuals experiencing this condition. Efforts to understand COVID-19 in people with HIV have led to novel insights into the biology and natural history of SARS-CoV-2 coinfection in this vulnerable subpopulation. These and other studies are summarized herein.}, } @article {pmid37315430, year = {2023}, author = {AlBahrani, S and AlBarrak, A and AlGubaisi, N and Alkurdi, H and Alburaiki, D and AlGhamdi, A and AlOthaiqy, M and Tayeb, S and Tayeb, N and Abdraboh, S and Khairi, A and Alshareef, L and AlHarbi, A and AlRabeeah, S and Alqahtani, AS and Alqahtani, JS and Hakami, FH and Al-Maqati, TN and Alkhrashi, SA and Almershad, MM and AlAbbadi, A and Hakami, MH and Faqihi, O and Altawfiq, KJA and Jebakumar, AZ and Al-Tawfiq, JA}, title = {Self-reported long COVID-19 symptoms are rare among vaccinated healthcare workers.}, journal = {Journal of infection and public health}, volume = {16}, number = {8}, pages = {1276-1280}, pmid = {37315430}, issn = {1876-035X}, mesh = {Humans ; Adult ; Self Report ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Cough ; Pandemics ; Post-Acute COVID-19 Syndrome ; Diarrhea ; Health Personnel ; }, abstract = {INTRODUCTION: COVID-19 pandemic adversely affected healthcare workers (HCWs). Here, we evaluate the occurence of long-COVID-19 symtoms among HCWs.

METHODS: This is a questionnaire-based study of HCWs who had COVID-19 in two medical centers in Saudi Arabia and were mostly vaccinated.

RESULTS: The study included 243 HCWs with a mean age (+ SD) of 36.1 (+ 7.6) years. Of them, 223 (91.8%) had three doses of COVID-19 vaccine, 12 (4.9%) had four doses, and 5 (2.1%) had two doses. The most common symptoms at the start of the illness were cough (180, 74.1%), shortness of breath (124, 51%), muscle ache (117, 48.1%), headache (113, 46.5%), sore throat (111, 45.7%), diarrhea (109, 44.9%) and loss of taste (108, 44.4%). Symptoms lasted for< one week in 117 (48.1%),> one week and< 1 month in 89 (36.6%),> 2 months and< 3 months in 9 (3.7%), and> 3 months in 15 (6.2%). The main symptoms present> 3 months were hair loss (8, 3.3%), cough (5, 2.1%), and diarrhea (5, 2.1%). A binomial regression analysis showed no relationship between persistence of symptoms for> 3 months and other demographic or clinical symptoms characteristics.

CONCLUSION: The study showed a low rate of the occurence of long-COVID> 3 months during the Omicron-wave among mostly vaccinated HCWs with no significant comorbidities. Furhter studies are needed to examine the effect of different vaccines on long-COVID-19 among HCWs.}, } @article {pmid37315370, year = {2023}, author = {Imam, MT and Almalki, ZS and Alzahrani, AR and Al-Ghamdi, SS and Falemban, AH and Alanazi, IM and Shahzad, N and Muhammad Alrooqi, M and Jabeen, Q and Shahid, I}, title = {COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications.}, journal = {International immunopharmacology}, volume = {121}, number = {}, pages = {110439}, pmid = {37315370}, issn = {1878-1705}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; *Liver Diseases/metabolism ; }, abstract = {COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.}, } @article {pmid37314982, year = {2023}, author = {Tsuchida, T and Sasaki, N and Ohira, Y}, title = {Low brain blood flow finding on SPECT in long COVID patients with brain fog.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {116}, number = {10}, pages = {877-878}, doi = {10.1093/qjmed/hcad135}, pmid = {37314982}, issn = {1460-2393}, } @article {pmid37313412, year = {2023}, author = {Visvabharathy, L and Hanson, BA and Orban, ZS and Lim, PH and Palacio, NM and Jimenez, M and Clark, JR and Graham, EL and Liotta, EM and Tachas, G and Penaloza-MacMaster, P and Koralnik, IJ}, title = {Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1155770}, pmid = {37313412}, issn = {1664-3224}, support = {K23 AG078705/AG/NIA NIH HHS/United States ; DP2 DA051912/DA/NIDA NIH HHS/United States ; U54 EB027049/EB/NIBIB NIH HHS/United States ; T32 AR007611/AR/NIAMS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *CD4-Positive T-Lymphocytes ; *CD8-Positive T-Lymphocytes ; *COVID-19/immunology ; Interleukin-6 ; *Post-Acute COVID-19 Syndrome/immunology ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents.

RESULTS: We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4[+] T cell responses and diminished CD8[+] memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8[+] T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction.

DISCUSSION: We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.}, } @article {pmid37311808, year = {2023}, author = {Hastie, CE and Lowe, DJ and McAuley, A and Mills, NL and Winter, AJ and Black, C and Scott, JT and O'Donnell, CA and Blane, DN and Browne, S and Ibbotson, TR and Pell, JP}, title = {Natural history of long-COVID in a nationwide, population cohort study.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3504}, pmid = {37311808}, issn = {2041-1723}, support = {COV/LTE/20/06/CSO_/Chief Scientist Office/United Kingdom ; MC_PC_20029/MRC_/Medical Research Council/United Kingdom ; MC_UU_00034/6/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cohort Studies ; SARS-CoV-2 ; *Deafness ; }, abstract = {Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.}, } @article {pmid37310901, year = {2023}, author = {Wan, EYF and Zhang, R and Mathur, S and Yan, VKC and Lai, FTT and Chui, CSL and Li, X and Wong, CKH and Chan, EWY and Lau, CS and Wong, ICK}, title = {Post-acute sequelae of COVID-19 in older persons: multi-organ complications and mortality.}, journal = {Journal of travel medicine}, volume = {30}, number = {5}, pages = {}, doi = {10.1093/jtm/taad082}, pmid = {37310901}, issn = {1708-8305}, support = {//AIR@InnoHK administered by Innovation and Technology Commission/ ; //Laboratory of Data Discovery for Health (D24H)/ ; //Research Grant from the Health Bureau, the HKSAR Government/ ; //Collaborative Research Fund, University Grants Committee, the HKSAR Government/ ; //HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government/ ; }, mesh = {Aged ; Humans ; *Cardiovascular Diseases/epidemiology ; *COVID-19/complications ; Disease Progression ; Hong Kong/epidemiology ; Middle Aged ; Male ; Female ; }, abstract = {INTRODUCTION: Evidence on long-term associations between coronavirus disease 2019 (COVID-19) and risks of multi-organ complications and mortality in older population is limited. This study evaluates these associations.

RESEARCH DESIGN AND METHODS: The cohorts included patients aged ≥60 year diagnosed with COVID-19 infection (cases), between 16 March 2020 and 31 May 2021 from the UK Biobank; and between 01 April 2020 and 31 May 2022 from the electronic health records in Hong Kong. Each patient was randomly matched with individuals without COVID-19 infection based on year of birth and sex and were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK cohort. Patients with COVID-19 infection over 6 months after the date of last dose of vaccination and their corresponding controls were excluded from our study. Characteristics between cohorts were further adjusted with Inverse Probability Treatment Weighting. For evaluating long-term association of COVID-19 with multi-organ disease complications and mortality after 21-days of diagnosis, Cox regression was employed.

RESULT: 10,759 (UKB) and 165,259 (HK) older adults with COVID-19 infection with matched 291,077 (UKB) and 1,100,394 (HK) non-COVID-19-diagnosed older adults were recruited. Older adults with COVID-19 were associated with a significantly higher risk of cardiovascular outcomes [major cardiovascular disease (stroke, heart failure and coronary heart disease): hazard ratio(UKB): 1.4 (95% Confidence interval: 1.1,1.6), HK:1.2 (95% CI: 1.1,1.3)]; myocardial infarction: HR(UKB): 1.8 (95% CI: 1.3,2.4), HK:1.2 (95% CI: 1.0,1.4)]; respiratory outcomes [interstitial lung disease: HR(UKB: 3.4 (95% CI: 2.5,4.5), HK: 4.0 (95% CI: 1.3,12.8); chronic pulmonary disease: HR(UKB): 1.7 (95% CI: 1.3,2.2), HK:1.6 (95% CI: 1.3,2.1)]; neuropsychiatric outcomes [seizure: HR(UKB): 2.6 (95% CI: 1.7,4.1), HK: 1.6 (95% CI: 1.2,2.1)]; and renal outcomes [acute kidney disease: HR(UKB): 1.4 (95% CI: 1.1,1.6), HK:1.6 (95% CI: 1.3,2.1)]; and all-cause mortality [HR(UKB): 4.9 (95% CI: 4.4,5.4), HK:2.5 (95% CI: 2.5,2.6)].

CONCLUSION: COVID-19 is associated with long-term risks of multi-organ complications in older adults (aged ≥ 60). Infected patients in this age-group may benefit from appropriate monitoring of signs/symptoms for developing these complications.}, } @article {pmid37310140, year = {2023}, author = {Dobrowolska, K and Zarębska-Michaluk, D and Poniedziałek, B and Jaroszewicz, J and Flisiak, R and Rzymski, P}, title = {Overview of autoantibodies in COVID-19 convalescents.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28864}, doi = {10.1002/jmv.28864}, pmid = {37310140}, issn = {1096-9071}, mesh = {Adult ; Humans ; Autoantibodies ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Seroepidemiologic Studies ; *Blood Group Antigens ; }, abstract = {Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.}, } @article {pmid37310006, year = {2023}, author = {Santopaolo, M and Gregorova, M and Hamilton, F and Arnold, D and Long, A and Lacey, A and Oliver, E and Halliday, A and Baum, H and Hamilton, K and Milligan, R and Pearce, O and Knezevic, L and Morales Aza, B and Milne, A and Milodowski, E and Jones, E and Lazarus, R and Goenka, A and Finn, A and Maskell, N and Davidson, AD and Gillespie, K and Wooldridge, L and Rivino, L}, title = {Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37310006}, issn = {2050-084X}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/V027506/1/MRC_/Medical Research Council/United Kingdom ; Elizabeth Blackwell Institute (EBI) with funding from the University's alumni and friends/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; CD8-Positive T-Lymphocytes ; SARS-CoV-2/metabolism ; Cytokines/metabolism ; }, abstract = {Coronavirus disease-19 (COVID-19) causes immune perturbations which may persist long term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate, or severe disease and investigated whether it associates with long COVID. At 3 months, patients with severe disease displayed persistent activation of CD4[+] and CD8[+] T-cells, based on expression of HLA-DR, CD38, Ki67, and granzyme B, and elevated plasma levels of interleukin-4 (IL-4), IL-7, IL-17, and tumor necrosis factor-alpha (TNF-α) compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation. Patients with severe disease reported a higher number of long COVID symptoms which did not however correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex, and disease severity. Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.}, } @article {pmid37307567, year = {2023}, author = {Min, Y and Wei, X and Peng, X}, title = {Letter to the Editor From Min et al: "Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors".}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {1}, pages = {e434-e435}, doi = {10.1210/clinem/dgad325}, pmid = {37307567}, issn = {1945-7197}, support = {2021YFE0206600//National Key Research and Development Program of China/ ; 82172842//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Vitamin D ; Survivors ; }, } @article {pmid37307214, year = {2023}, author = {di Filippo, L and Frara, S and Giustina, A}, title = {Response to the Letter to the Editor From Min et al: Low Vitamin D Levels are Associated With Long COVID Syndrome in COVID-19 Survivors.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {1}, pages = {e438-e439}, doi = {10.1210/clinem/dgad327}, pmid = {37307214}, issn = {1945-7197}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Vitamin D ; *Vitamin D Deficiency/complications ; Survivors ; }, } @article {pmid37304792, year = {2023}, author = {Baker, AME and Maffitt, NJ and Del Vecchio, A and McKeating, KM and Baker, MR and Baker, SN and Soteropoulos, DS}, title = {Neural dysregulation in post-COVID fatigue.}, journal = {Brain communications}, volume = {5}, number = {3}, pages = {fcad122}, pmid = {37304792}, issn = {2632-1297}, support = {MR/W004798/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Following infection with SARS-CoV-2, a substantial minority of people develop lingering after-effects known as 'long COVID'. Fatigue is a common complaint with a substantial impact on daily life, but the neural mechanisms behind post-COVID fatigue remain unclear. We recruited 37 volunteers with self-reported fatigue after a mild COVID infection and carried out a battery of behavioural and neurophysiological tests assessing the central, peripheral and autonomic nervous systems. In comparison with age- and sex-matched volunteers without fatigue (n = 52), we show underactivity in specific cortical circuits, dysregulation of autonomic function and myopathic change in skeletal muscle. Cluster analysis revealed no subgroupings, suggesting post-COVID fatigue is a single entity with individual variation, rather than a small number of distinct syndromes. Based on our analysis, we were also able to exclude dysregulation in sensory feedback circuits and descending neuromodulatory control. These abnormalities on objective tests may aid in the development of novel approaches for disease monitoring.}, } @article {pmid37303754, year = {2023}, author = {Cocciolillo, F and Chieffo, DPR and Giordano, A and Arcangeli, V and Lazzareschi, I and Morello, R and Zampino, G and Valentini, P and Buonsenso, D}, title = {Case report: Post-COVID new-onset neurocognitive decline with bilateral mesial-temporal hypometabolism in two previously healthy sisters.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1165072}, pmid = {37303754}, issn = {2296-2360}, abstract = {BACKGROUND: Long coronavirus disease (COVID) is increasingly recognized in adults and children; however, it is still poorly characterized from a clinical and diagnostic perspective, particularly in the younger populations.

CASE PRESENTATION: We described the story of two sisters-with high social and academic performance before their severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-who reported severe neurocognitive problems, initially classified as psychologic pandemic distress and eventually found to have significant brain hypometabolism.

CONCLUSIONS: We provided a detailed clinical presentation of neurocognitive symptoms in two sisters with long COVID associated with brain hypometabolism documented in both sisters. We believe that the evidence of objective findings in these children further supports the hypothesis that organic events cause persisting symptoms in a cohort of children after SARS-CoV-2 infection. Such findings highlight the importance of discovering diagnostics and therapeutics.}, } @article {pmid37303262, year = {2023}, author = {Kleebayoon, A and Wiwanitkit, V}, title = {The experience of Black Americans with long COVID: Comment.}, journal = {Journal of clinical nursing}, volume = {32}, number = {23-24}, pages = {8153}, doi = {10.1111/jocn.16784}, pmid = {37303262}, issn = {1365-2702}, mesh = {Humans ; *Black or African American ; COVID-19 ; *Post-Acute COVID-19 Syndrome/ethnology ; SARS-CoV-2 ; White ; }, } @article {pmid37302434, year = {2023}, author = {Salfi, F and Amicucci, G and Corigliano, D and Viselli, L and D'Atri, A and Tempesta, D and Ferrara, M}, title = {Poor sleep quality, insomnia, and short sleep duration before infection predict long-term symptoms after COVID-19.}, journal = {Brain, behavior, and immunity}, volume = {112}, number = {}, pages = {140-151}, pmid = {37302434}, issn = {1090-2139}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/epidemiology ; *COVID-19 ; Prospective Studies ; Sleep Quality ; Sleep Duration ; Retrospective Studies ; SARS-CoV-2 ; Sleep ; }, abstract = {BACKGROUND: Millions of COVID-19 survivors experience a wide range of long-term symptoms after acute infection, giving rise to serious public health concerns. To date, few risk factors for post-COVID-19 conditions have been determined. This study evaluated the role of pre-infection sleep quality/duration and insomnia severity in the incidence of long-term symptoms after COVID-19.

MATERIAL AND METHODS: This prospective study involved two assessments (April 2020 and 2022). At the baseline (April 2020), sleep quality/duration and insomnia symptoms in participants without current/prior SARS-CoV-2 infection were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). At the follow-up (April 2022), we asked a group of COVID-19 survivors to retrospectively evaluate the presence of twenty-one symptoms (psychiatric, neurological, cognitive, bodily, and respiratory) that have been experienced one month (n = 713, infection in April 2020-February 2022) and three months after COVID-19 (n = 333, infection in April 2020-December 2021). In April 2022, participants also reported how many weeks passed to fully recover from COVID-19. Zero-inflated negative binomial models were used to estimate the effect of previous sleep on the number of long-term symptoms. Binomial logistic regressions were performed to evaluate the association between sleep variables, the incidence of each post-COVID-19 symptom, and the odds of recovery four/twelve weeks after infection.

RESULTS: Analyses highlighted a significant effect of pre-infection sleep on the number of symptoms one/three months after COVID-19. Previous higher PSQI and ISI scores, and shorter sleep duration significantly increased the risk of almost every long-term symptom at one/three months from COVID-19. Baseline sleep problems were also associated with longer recovery times to return to the pre-infection daily functioning level after COVID-19.

CONCLUSIONS: This study suggested a prospective dose-dependent association of pre-infection sleep quality/quantity and insomnia severity with the manifestation of post-COVID-19 symptoms. Further research is warranted to determine whether preventively promoting sleep health may mitigate the COVID-19 sequelae, with substantial public health and societal implications.}, } @article {pmid37302406, year = {2023}, author = {Bramante, CT and Buse, JB and Liebovitz, DM and Nicklas, JM and Puskarich, MA and Cohen, K and Belani, HK and Anderson, BJ and Huling, JD and Tignanelli, CJ and Thompson, JL and Pullen, M and Wirtz, EL and Siegel, LK and Proper, JL and Odde, DJ and Klatt, NR and Sherwood, NE and Lindberg, SM and Karger, AB and Beckman, KB and Erickson, SM and Fenno, SL and Hartman, KM and Rose, MR and Mehta, T and Patel, B and Griffiths, G and Bhat, NS and Murray, TA and Boulware, DR and , }, title = {Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {10}, pages = {1119-1129}, pmid = {37302406}, issn = {1474-4457}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; T32 HL129956/HL/NHLBI NIH HHS/United States ; R21 LM012744/LM/NLM NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; R01 LM012982/LM/NLM NIH HHS/United States ; K23 HL133604/HL/NHLBI NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Pregnancy ; Humans ; Male ; Female ; Middle Aged ; *COVID-19 ; Incidence ; Ivermectin/therapeutic use ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Fluvoxamine ; Outpatients ; SARS-CoV-2 ; *Metformin/therapeutic use ; Double-Blind Method ; Treatment Outcome ; }, abstract = {BACKGROUND: Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.

METHODS: We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194.

FINDINGS: Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and median BMI was 29·8 kg/m[2] (IQR 27·0-34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2-8·2) in participants who received metformin and 10·4% (7·8-12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39-0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15-0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59-1·64) or fluvoxamine (1·36, 0·78-2·34) compared with placebo.

INTERPRETATION: Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.

FUNDING: Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.}, } @article {pmid37302405, year = {2023}, author = {Faust, JS}, title = {The therapeutic validation of long COVID.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {10}, pages = {1096-1097}, pmid = {37302405}, issn = {1474-4457}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, } @article {pmid37301958, year = {2023}, author = {Iosef, C and Knauer, MJ and Nicholson, M and Van Nynatten, LR and Cepinskas, G and Draghici, S and Han, VKM and Fraser, DD}, title = {Plasma proteome of Long-COVID patients indicates HIF-mediated vasculo-proliferative disease with impact on brain and heart function.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {377}, pmid = {37301958}, issn = {1479-5876}, mesh = {Humans ; *COVID-19 ; Proteome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Brain ; Biomarkers ; }, abstract = {AIMS: Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aimed to unveil potential mechanisms, and to inform prognosis and treatment.

METHODS: Plasma proteome from Long-COVID outpatients was analyzed in comparison to matched acutely ill COVID-19 (mild and severe) inpatients and healthy control subjects. The expression of 3072 protein biomarkers was determined with proximity extension assays and then deconvoluted with multiple bioinformatics tools into both cell types and signaling mechanisms, as well as organ specificity.

RESULTS: Compared to age- and sex-matched acutely ill COVID-19 inpatients and healthy control subjects, Long-COVID outpatients showed natural killer cell redistribution with a dominant resting phenotype, as opposed to active, and neutrophils that formed extracellular traps. This potential resetting of cell phenotypes was reflected in prospective vascular events mediated by both angiopoietin-1 (ANGPT1) and vascular-endothelial growth factor-A (VEGFA). Several markers (ANGPT1, VEGFA, CCR7, CD56, citrullinated histone 3, elastase) were validated by serological methods in additional patient cohorts. Signaling of transforming growth factor-β1 with probable connections to elevated EP/p300 suggested vascular inflammation and tumor necrosis factor-α driven pathways. In addition, a vascular proliferative state associated with hypoxia inducible factor 1 pathway suggested progression from acute COVID-19 to Long-COVID. The vasculo-proliferative process predicted in Long-COVID might contribute to changes in the organ-specific proteome reflective of neurologic and cardiometabolic dysfunction.

CONCLUSIONS: Taken together, our findings point to a vasculo-proliferative process in Long-COVID that is likely initiated either prior hypoxia (localized or systemic) and/or stimulatory factors (i.e., cytokines, chemokines, growth factors, angiotensin, etc). Analyses of the plasma proteome, used as a surrogate for cellular signaling, unveiled potential organ-specific prognostic biomarkers and therapeutic targets.}, } @article {pmid37300737, year = {2023}, author = {Lesnak, JB and Mazhar, K and Price, TJ}, title = {Neuroimmune Mechanisms Underlying Post-acute Sequelae of SARS-CoV-2 (PASC) Pain, Predictions from a Ligand-Receptor Interactome.}, journal = {Current rheumatology reports}, volume = {25}, number = {9}, pages = {169-181}, pmid = {37300737}, issn = {1534-6307}, support = {U19 NS130608/NS/NINDS NIH HHS/United States ; U19NS130608/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2 ; Neuroimmunomodulation ; *COVID-19/complications ; Ligands ; Disease Progression ; *Musculoskeletal Pain ; }, abstract = {PURPOSE OF REVIEW: Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms.

RECENT FINDINGS: To generate hypotheses regarding neuroimmune interactions in PASC, we used a ligand-receptor interactome to make predictions about how ligands from PBMCs in individuals with COVID-19 communicate with dorsal root ganglia (DRG) neurons to induce persistent pain. In a structured literature review of -omics COVID-19 studies, we identified ligands capable of binding to receptors on DRG neurons, which stimulate signaling pathways including immune cell activation and chemotaxis, the complement system, and type I interferon signaling. The most consistent finding across immune cell types was an upregulation of genes encoding the alarmins S100A8/9 and MHC-I. This ligand-receptor interactome, from our hypothesis-generating literature review, can be used to guide future research surrounding mechanisms of PASC-induced pain.}, } @article {pmid37298527, year = {2023}, author = {Bicknell, B and Liebert, A and Borody, T and Herkes, G and McLachlan, C and Kiat, H}, title = {Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298527}, issn = {1422-0067}, mesh = {Animals ; Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/metabolism ; *Autism Spectrum Disorder/metabolism ; Dysbiosis/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; *Microbiota ; Brain/metabolism ; }, abstract = {The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.}, } @article {pmid37297898, year = {2023}, author = {Salvato, G and Inglese, E and Fazia, T and Crottini, F and Crotti, D and Valentini, F and Palmas, G and Bollani, A and Basilico, S and Gandola, M and Gelosa, G and Gentilini, D and Bernardinelli, L and Stracciari, A and Scaglione, F and Agostoni, EC and Bottini, G}, title = {The Association between Dysnatraemia during Hospitalisation and Post-COVID-19 Mental Fatigue.}, journal = {Journal of clinical medicine}, volume = {12}, number = {11}, pages = {}, pmid = {37297898}, issn = {2077-0383}, abstract = {COVID-19 may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still controversial. Here, we investigated whether (i) the odds of experiencing persistent cognitive failures differ based on the patients' disease course severity and sex at birth; and (ii) the patients' electrolytic profile in the acute stage represents a risk factor for persistent cognitive failures. We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS scale, their disease course was classified as severe or mild. We investigated the presence of persistent cognitive failures collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. The results showed that females who suffered from a mild course compared to a severe course of COVID-19 had a higher risk of presenting with persistent mental fatigue after recovery. Furthermore, in females who suffered from a mild course of COVID-19, persistent mental fatigue was related to electrolyte imbalance, in terms of both hypo- and hypernatremia, during hospitalisation in the acute phase. These findings have important implications for the clinical management of hospitalised COVID-19 patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19.}, } @article {pmid37297812, year = {2023}, author = {Kisiel, MA and Lee, S and Malmquist, S and Rykatkin, O and Holgert, S and Janols, H and Janson, C and Zhou, X}, title = {Clustering Analysis Identified Three Long COVID Phenotypes and Their Association with General Health Status and Working Ability.}, journal = {Journal of clinical medicine}, volume = {12}, number = {11}, pages = {}, pmid = {37297812}, issn = {2077-0383}, support = {2022//Åke Wibergs Stiftelse/ ; 2022//Lars Hiertas Minne Stiftelse/ ; 2022//Sven och Dagmar Salén Stiftelse/ ; 2021//Tore Nilsons Stiftelsen/ ; }, abstract = {BACKGROUND/AIM: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID.

METHOD: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes.

RESULTS: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype.

CONCLUSION: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.}, } @article {pmid37297733, year = {2023}, author = {Aprile, I and Bramante, L and La Russa, C and Germanotta, M and Barletta, VT and Falchini, F and Brambilla, L and Guglielmelli, E and Rossi, P}, title = {A Multiaxial Rehabilitation Programme for Workers with COVID-19 Sequelae Using a Conventional and Technological-Robotic Approach: The Proposal of INAIL and Fondazione Don Carlo Gnocchi.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {37297733}, issn = {2227-9032}, abstract = {The COVID-19 sequelae have been shown to affect respiratory and cardiological functions as well as neuro-psychological functions, and, in some cases, metabolic/nutritional aspects. The Italian National Institute for Insurance against Accidents at Work (Istituto Nazionale Assicurazione Infortuni sul Lavoro, INAIL) recorded that, until December 2022, 315,055 workers were affected by COVID-19; therefore, there is a need to identify an effective approach to treat such patients. Robotic and technological devices could be integrated into the rehabilitation programme of people with long COVID conditions. A review of the literature showed that telerehabilitation may improve functional capacity, dyspnoea, performance, and quality of life in these patients, but no studies were found evaluating the effects of robot-mediated therapy or virtual reality systems. Considering the above, Fondazione Don Carlo Gnocchi and INAIL propose a multi-axial rehabilitation for workers with COVID-19 sequelae. To accomplish this goal, the two institutions merged the epidemiological information gathered by INAIL, the expertise in robotic and technological rehabilitation of Fondazione Don Carlo Gnocchi, and the literature review. Our proposal aims to facilitate a multi-axial rehabilitation approach customized to meet the unique needs of each individual, with a particular emphasis on utilizing advanced technologies to address the current and future challenges of patient care.}, } @article {pmid37296140, year = {2023}, author = {Frisk, B and Jürgensen, M and Espehaug, B and Njøten, KL and Søfteland, E and Aarli, BB and Kvale, G}, title = {A safe and effective micro-choice based rehabilitation for patients with long COVID: results from a quasi-experimental study.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {9423}, pmid = {37296140}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/complications/rehabilitation ; Dyspnea ; Fatigue ; Longitudinal Studies ; *Post-Acute COVID-19 Syndrome/rehabilitation ; Quality of Life ; Adult ; Middle Aged ; Aged ; }, abstract = {At least 65 million people suffer from long COVID. Treatment guidelines are unclear, especially pertaining to recommendations of increased activity. This longitudinal study evaluated safety, changes in functional level and sick leave following a concentrated rehabilitation program for patients with long COVID. Seventy-eight patients (19-67 years) participated in a 3-day micro-choice based rehabilitation program with 7-day and 3-month follow-up. Fatigue, functional levels, sick leave, dyspnea and exercise capacity were assessed. No adverse events were reported and 97.4% completed the rehabilitation. Fatigue measured with Chalder Fatigue Questionnaire decreased at 7-days [mean difference (MD = - 4.5, 95% CI - 5.5 to - 3.4) and 3-month (MD = - 5.5, 95% CI - 6.7 to - 4.3). Sick leave rates and dyspnea were reduced (p < 0.001) and exercise capacity and functional level increased (p < 0.001) at 3-month follow-up regardless of severity of fatigue at baseline. Micro-choice based concentrated rehabilitation for patients with long COVID was safe, highly acceptable and showed rapid improvements in fatigue and functional levels, sustaining over time. Even though this is a quasi-experimental study, the findings are of importance addressing the tremendous challenges of disability due to long COVID. Our results are also highly relevant for patients, as they provide the base for an optimistic outlook and evidence supported reason for hope.}, } @article {pmid37296110, year = {2023}, author = {Talla, A and Vasaikar, SV and Szeto, GL and Lemos, MP and Czartoski, JL and MacMillan, H and Moodie, Z and Cohen, KW and Fleming, LB and Thomson, Z and Okada, L and Becker, LA and Coffey, EM and De Rosa, SC and Newell, EW and Skene, PJ and Li, X and Bumol, TF and Juliana McElrath, M and Torgerson, TR}, title = {Persistent serum protein signatures define an inflammatory subcategory of long COVID.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3417}, pmid = {37296110}, issn = {2041-1723}, support = {UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI069481/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Blood Proteins ; Disease Progression ; Inflammation ; }, abstract = {Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals. Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature. These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.}, } @article {pmid37295581, year = {2023}, author = {Rodriguez-Morales, AJ and Lopez-Echeverri, MC and Perez-Raga, MF and Quintero-Romero, V and Valencia-Gallego, V and Galindo-Herrera, N and López-Alzate, S and Sánchez-Vinasco, JD and Gutiérrez-Vargas, JJ and Mayta-Tristan, P and Husni, R and Moghnieh, R and Stephan, J and Faour, W and Tawil, S and Barakat, H and Chaaban, T and Megarbane, A and Rizk, Y and Sakr, R and Escalera-Antezana, JP and Alvarado-Arnez, LE and Bonilla-Aldana, DK and Camacho-Moreno, G and Mendoza, H and Rodriguez-Sabogal, IA and Millán-Oñate, J and Lopardo, G and Barbosa, AN and Cimerman, S and Chaves, TDSS and Orduna, T and Lloveras, S and Rodriguez-Morales, AG and Thormann, M and Zambrano, PG and Perez, C and Sandoval, N and Zambrano, L and Alvarez-Moreno, CA and Chacon-Cruz, E and Villamil-Gomez, WE and Benites-Zapata, V and Savio-Larriera, E and Cardona-Ospina, JA and Risquez, A and Forero-Peña, DA and Henao-Martínez, AF and Sah, R and Barboza, JJ and León-Figueroa, DA and Acosta-España, JD and Carrero-Gonzalez, CM and Al-Tawfiq, JA and Rabaan, AA and Leblebicioglu, H and Gonzales-Zamora, JA and Ulloa-Gutiérrez, R}, title = {The global challenges of the long COVID-19 in adults and children.}, journal = {Travel medicine and infectious disease}, volume = {54}, number = {}, pages = {102606}, pmid = {37295581}, issn = {1873-0442}, mesh = {Adult ; Child ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid37294977, year = {2023}, author = {Kachaner, A and Lemogne, C and Ranque, B and Meppiel, E and de Broucker, T}, title = {Response to 'Functional neurological disorder in people with long COVID: A systematic review'.}, journal = {European journal of neurology}, volume = {30}, number = {9}, pages = {2949-2950}, doi = {10.1111/ene.15911}, pmid = {37294977}, issn = {1468-1331}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Conversion Disorder ; }, } @article {pmid37293829, year = {2023}, author = {Báez-Suárez, A and González Montañez, C and Esparza Ferrera, CE and Dorta Martín, G and Quintana-Montesdeoca, MDP}, title = {[Evaluation of patients with long covid in the canarian population: study protocol.].}, journal = {Revista espanola de salud publica}, volume = {97}, number = {}, pages = {}, pmid = {37293829}, issn = {2173-9110}, mesh = {*COVID-19/epidemiology ; Pandemics/prevention & control ; SARS-CoV-2 ; Spain/epidemiology ; Observational Studies as Topic ; Humans ; Post-Acute COVID-19 Syndrome ; European People ; Treatment Outcome ; }, abstract = {The current COVID-19 pandemic has generated a relevant changes in the normal development of human performance. Some changes detected in SARS-CoV-2 infected people have to do with possible effects of the infection in the bio-psycho-social sphere. The population in the Autonomous Community of the Canary Islands has not been oblivious to it and, therefore, a need demanded by society has roared. A multicentre observational study will be carried out to assess the physical and functional status of people from the Canary Islands who, after being infected with the SARS-CoV-2 virus, suffer sequelae that persist after twelve weeks of infection. With help from the Official Association of Physiotherapists of the Canary Islands a call will be made to the population. This association will oversee the dissemination of the information and will recruit among its members the collaborating/evaluating physiotherapists, also ensuring the protection and preservation of the data to be collected. People meeting the established criteria will be referred to the more accessible collaborating centre of the canarian community, where, after a preliminary interview, participating patients will self-complete scientifically validated questionnaires, and will be subjected to different validated tests to evaluate their physical and functional status. Patients will be individually informed of the results of their evaluation, and they will receive a dossier with individualized recommendations. After this evaluation, a follow-up of the participants for up to 6 months is anticipated. Data will be recorded, analysed, and interpreted, and the results will be disseminated through conventional means of communication to society and also by attempting publication in scientific journals.}, } @article {pmid37293307, year = {2023}, author = {Smith, JL and Deighton, K and Innes, AQ and Holl, M and Mould, L and Liao, Z and Doherty, P and Whyte, G and King, JA and Deniszczyc, D and Kelly, BM}, title = {Improved clinical outcomes in response to a 12-week blended digital and community-based long-COVID-19 rehabilitation programme.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1149922}, pmid = {37293307}, issn = {2296-858X}, abstract = {INTRODUCTION: Two million people in the UK are experiencing long COVID (LC), which necessitates effective and scalable interventions to manage this condition. This study provides the first results from a scalable rehabilitation programme for participants presenting with LC.

METHODS: 601 adult participants with symptoms of LC completed the Nuffield Health COVID-19 Rehabilitation Programme between February 2021 and March 2022 and provided written informed consent for the inclusion of outcomes data in external publications. The 12-week programme included three exercise sessions per week consisting of aerobic and strength-based exercises, and stability and mobility activities. The first 6 weeks of the programme were conducted remotely, whereas the second 6 weeks incorporated face-to-face rehabilitation sessions in a community setting. A weekly telephone call with a rehabilitation specialist was also provided to support queries and advise on exercise selection, symptom management and emotional wellbeing.

RESULTS: The 12-week rehabilitation programme significantly improved Dyspnea-12 (D-12), Duke Activity Status Index (DASI), World Health Orginaisation-5 (WHO-5) and EQ-5D-5L utility scores (all p < 0.001), with the 95% confidence intervals (CI) for the improvement in each of these outcomes exceeding the minimum clinically important difference (MCID) for each measure (mean change [CI]: D-12: -3.4 [-3.9, -2.9]; DASI: 9.2 [8.2, 10.1]; WHO-5: 20.3 [18.6, 22.0]; EQ-5D-5L utility: 0.11 [0.10, 0.13]). Significant improvements exceeding the MCID were also observed for sit-to-stand test results (4.1 [3.5, 4.6]). On completion of the rehabilitation programme, participants also reported significantly fewer GP consultations (p < 0.001), sick days (p = 0.003) and outpatient visits (p = 0.007) during the previous 3 months compared with baseline.

DISCUSSION: The blended and community design of this rehabilitation model makes it scalable and meets the urgent need for an effective intervention to support patients experiencing LC. This rehabilitation model is well placed to support the NHS (and other healthcare systems worldwide) in its aim of controlling the impacts of COVID-19 and delivering on its long-term plan.

CLINICAL TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN14707226, identifier 14707226.}, } @article {pmid37292432, year = {2023}, author = {Montani, D and Savale, L and Noel, N and Meyrignac, O and Colle, R and Gasnier, M and Corruble, E and Beurnier, A and Jutant, EM and Pham, T and Lecoq, AL and Papon, JF and Figuereido, S and Harrois, A and Humbert, M and Monnet, X and , }, title = {[Post-COVID-19 syndrome].}, journal = {Bulletin de l'Academie nationale de medecine}, volume = {207}, number = {6}, pages = {812-820}, pmid = {37292432}, issn = {0001-4079}, abstract = {In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.}, } @article {pmid37292374, year = {2023}, author = {Lokanuwatsatien, T and Satdhabudha, A and Tangsathapornpong, A and Bunjoungmanee, P and Sinlapamongkolkul, P and Chaiyakulsil, C and Sritipsukho, P and Tantiyavarong, P}, title = {Prevalence and associating factors of long COVID in pediatric patients during the Delta and the Omicron variants.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1127582}, pmid = {37292374}, issn = {2296-2360}, abstract = {INTRODUCTION: The number of pediatric COVID-19 infections is increasing; however, the data on long COVID conditions in children is still limited. Our study aimed to find the prevalence of long COVID in children during the Delta and Omicron waves, as well as associated factors.

METHODS: A single-center prospective cohort study was conducted. We included 802 RT-PCR-confirmed COVID-19 pediatric patients in the Delta and Omicron periods. Long COVID was defined as having symptoms for ≥3 months after infection. Parents and/or patients were interviewed by phone. Multivariable logistic regression was performed to find associated factors with long COVID.

RESULTS: The overall prevalence of long COVID was 30.2%. The Delta period had more prevalence than the Omicron (36.3% vs. 23.9%). Common symptoms for patients 0-3 years' old were loss of appetite, rhinorrhea, and nasal congestion. Conversely, patients 3-18 years' old had hair loss, dyspnea on exertion, rhinorrhea, and nasal congestion. However, there was no significant negative impact on daily life. Most symptoms improved after a 6-month follow-up. Factors associated with long COVID-19 conditions were infection during the Omicron period (adjusted OR: 0.54; 95% CI: 0.39-0.74, P < 0.001), fever (adjusted OR: 1.49, 95% CI: 1.01-2.20, P = 0.04) and rhinorrhea (adjusted OR: 1.47, 95% CI: 1.06-2.02, P = 0.02).

CONCLUSION: Infection during the Omicron wave has a lower prevalence of long COVID. The prognosis is often favorable, and most symptoms gradually become less. However, pediatricians may schedule appointments to surveil long COVID in children with fever or rhinorrhea as an initial symptom.}, } @article {pmid37291679, year = {2023}, author = {Silva, CA and de Vinci Kanda Kupa, L and Medeiros-Ribeiro, AC and Pasoto, SG and Saad, CGS and Yuki, EFN and Landim, JIVD and Léda, VHFE and de Camargo Correia, LS and Sartori, AF and Martins, CCMF and Ribeiro, CT and Waridel, F and de Oliveira Martins, VA and Shinjo, SK and Andrade, DCO and Sampaio-Barros, PD and Neto, EFB and Aikawa, NE and Bonfa, E}, title = {Post-acute COVID-19 in three doses vaccinated autoimmune rheumatic diseases patients: frequency and pattern of this condition.}, journal = {Advances in rheumatology (London, England)}, volume = {63}, number = {1}, pages = {26}, pmid = {37291679}, issn = {2523-3106}, mesh = {Humans ; *Autoimmune Diseases/drug therapy/epidemiology ; *COVID-19/epidemiology/prevention & control ; Prospective Studies ; Retrospective Studies ; *Rheumatic Diseases/drug therapy ; SARS-CoV-2 ; Male ; Female ; }, abstract = {BACKGROUND: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria.

METHODS: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria.

RESULTS: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations.

CONCLUSION: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).}, } @article {pmid37291610, year = {2023}, author = {Oliveira, JGM and Campos, RP and Azevedo, BLPA and de Alegria, SG and Litrento, PF and Mafort, TT and Lopes, AJ}, title = {Ventilation dynamics using a portable device coupled to the six-minute walk test in people with long-COVID syndrome: a preliminary study.}, journal = {BMC research notes}, volume = {16}, number = {1}, pages = {99}, pmid = {37291610}, issn = {1756-0500}, support = {#301967/2022-9//Conselho Nacional de Desenvolvimento Científico e Tecnólogico/ ; #E-26/211.024/2019, #E-26/211.187/2021, #E-26/211.104/2021, and #E-26/200.929/2022//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; Finance Code 001, 88881.708719/2022-01, and 88887.708718/2022-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; Walk Test ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Lung ; Walking/physiology ; Exercise Test/methods ; *Pulmonary Disease, Chronic Obstructive ; }, abstract = {OBJECTIVE: To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS).

RESULTS: Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4-20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386-478) m, which corresponds to a value of 83% (78-97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14-37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems.}, } @article {pmid37290316, year = {2023}, author = {Tsuzuki, S and Beutels, P}, title = {The estimated disease burden of COVID-19 in Japan from 2020 to 2021.}, journal = {Journal of infection and public health}, volume = {16}, number = {8}, pages = {1236-1243}, pmid = {37290316}, issn = {1876-035X}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Japan/epidemiology ; Cost of Illness ; Quality-Adjusted Life Years ; }, abstract = {BACKGROUND: To date, it is not fully understood to what extent COVID-19 has burdened society in Japan. This study aimed to estimate the total disease burden due to COVID-19 in Japan during 2020-2021.

METHODS: We stratify disease burden estimates by age group and present it as absolute Quality Adjusted Life Years (QALYs) lost and QALYs lost per 100,000 persons. The total estimated value of QALYs lost consists of (1) QALYs lost brought by deaths due to COVID-19, (2) QALYs lost brought by inpatient cases, (3) QALYs lost brought by outpatient cases, and (4) QALYs lost brought by long-COVID.

RESULTS: The total QALYs lost due to COVID-19 was estimated as 286,782 for two years, 114.0 QALYs per 100,000 population per year. 71.3% of them were explained by the burden derived from deaths. Probabilistic sensitivity analysis showed that the burden of outpatient cases was the most sensitive factor.

CONCLUSIONS: The large part of disease burden due to COVID-19 in Japan from the beginning of 2020 to the end of 2021 was derived from Wave 3, 4, and 5 and the proportion of QALYs lost due to morbidity in the total burden increased gradually. The estimated disease burden was smaller than that in other high-income countries. It will be our future challenge to take other indirect factors into consideration.}, } @article {pmid37288661, year = {2023}, author = {Bodansky, A and Wang, CY and Saxena, A and Mitchell, A and Kung, AF and Takahashi, S and Anglin, K and Huang, B and Hoh, R and Lu, S and Goldberg, SA and Romero, J and Tran, B and Kirtikar, R and Grebe, H and So, M and Greenhouse, B and Durstenfeld, MS and Hsue, PY and Hellmuth, J and Kelly, JD and Martin, JN and Anderson, MS and Deeks, SG and Henrich, TJ and DeRisi, JL and Peluso, MJ}, title = {Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.}, journal = {JCI insight}, volume = {8}, number = {11}, pages = {}, pmid = {37288661}, issn = {2379-3708}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K12 HD000850/HD/NICHD NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Autoantibodies ; Autoantigens ; }, abstract = {Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.}, } @article {pmid37288652, year = {2023}, author = {Rahmati, M and Udeh, R and Yon, DK and Lee, SW and Dolja-Gore, X and McEVoy, M and Kenna, T and Jacob, L and López Sánchez, GF and Koyanagi, A and Shin, JI and Smith, L}, title = {A systematic review and meta-analysis of long-term sequelae of COVID-19 2-year after SARS-CoV-2 infection: A call to action for neurological, physical, and psychological sciences.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28852}, doi = {10.1002/jmv.28852}, pmid = {37288652}, issn = {1096-9071}, mesh = {Humans ; Female ; Male ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Anxiety/epidemiology ; Carbon Monoxide ; Disease Progression ; }, abstract = {Long-term sequelae conditions of COVID-19 at least 2-year following SARS-CoV-2 infection are unclear and little is known about their prevalence, longitudinal trajectory, and potential risk factors. Therefore, we conducted a comprehensive meta-analysis of survivors' health-related consequences and sequelae at 2-year following SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to February 10, 2023. A systematic review and meta-analysis were performed to calculate the pooled effect size, expressed as event rate (ER) with corresponding 95% confidence interval (CI) of each outcome. Twelve studies involving 1 289 044 participants from 11 countries were included. A total of 41.7% of COVID-19 survivors experienced at least one unresolved symptom and 14.1% were unable to return to work at 2-year after SARS-CoV-2 infection. The most frequent symptoms and investigated findings at 2-year after SARS-CoV-2 infection were fatigue (27.4%; 95% CI 17%-40.9%), sleep difficulties (25.1%; 95% CI 22.4%-27.9%), impaired diffusion capacity for carbon monoxide (24.6%; 95% CI 10.8%-46.9%), hair loss (10.2%; 95% CI 7.3%-14.2%), and dyspnea (10.1%; 95% CI 4.3%-21.9%). Individuals with severe infection suffered more from anxiety (OR = 1.69, 95% CI 1.17-2.44) and had more impairments in forced vital capacity (OR = 9.70, 95% CI 1.94-48.41), total lung capacity (OR = 3.51, 95% CI 1.77-6.99), and residual volume (OR = 3.35, 95% CI 1.85-6.07) after recovery. Existing evidence suggest that participants with a higher risk of long-term sequelae were older, mostly female, had pre-existing medical comorbidities, with more severe status, underwent corticosteroid therapy, and higher inflammation at acute infection. Our findings suggest that 2-year after recovery from SARS-CoV-2 infection, 41.7% of survivors still suffer from either neurological, physical, and psychological sequela. These findings indicate that there is an urgent need to preclude persistent or emerging long-term sequelae and provide intervention strategies to reduce the risk of long COVID.}, } @article {pmid37287969, year = {2023}, author = {Damiano, RF and Rocca, CCA and Serafim, AP and Loftis, JM and Talib, LL and Pan, PM and Cunha-Neto, E and Kalil, J and de Castro, GS and Seelaender, M and Guedes, BF and Nagahashi Marie, SK and de Souza, HP and Nitrini, R and Miguel, EC and Busatto, G and Forlenza, OV}, title = {Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1174020}, pmid = {37287969}, issn = {1664-3224}, support = {I01 BX002061/BX/BLRD VA/United States ; }, mesh = {Adult ; Humans ; Female ; Middle Aged ; Aged ; Male ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction/epidemiology ; Cytokines ; }, abstract = {OBJECTIVE: To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19.

METHODS: We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers.

RESULTS: Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings.

CONCLUSION: Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.}, } @article {pmid37287942, year = {2023}, author = {Bechor Ariel, T and Ariel, B and Ben-Acon, M and Sharon, N}, title = {Focal and generalized onset seizures in children post-COVID (Omicron) recovery: 3 clinical case reports.}, journal = {Epilepsy & behavior reports}, volume = {23}, number = {}, pages = {100608}, pmid = {37287942}, issn = {2589-9864}, abstract = {Description of three cases of 4-7-year-old male children presenting with a seizure without a prior history of epilepsy, 2-4 weeks after recovering from COVID-19. All three children were admitted to the pediatric department at Laniado Hospital in Netanya, Israel, and presented with seizures without fever. We found common characteristics among the children that can imply a predisposition for neurological complications of Covid-19.}, } @article {pmid37287866, year = {2023}, author = {Hotez, P}, title = {Anti-science conspiracies pose new threats to US biomedicine in 2023.}, journal = {FASEB bioAdvances}, volume = {5}, number = {6}, pages = {228-232}, pmid = {37287866}, issn = {2573-9832}, } @article {pmid37287442, year = {2023}, author = {Kioi, Y and Yorifuji, H and Higami, Y and Katada, Y}, title = {Serositis and lymphopenia are common features of systemic lupus erythematosus following SARS-CoV-2 infection: A case report and literature review.}, journal = {International journal of rheumatic diseases}, volume = {26}, number = {11}, pages = {2267-2271}, doi = {10.1111/1756-185X.14767}, pmid = {37287442}, issn = {1756-185X}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Serositis/diagnosis/etiology ; *Lupus Erythematosus, Systemic/complications/diagnosis/drug therapy ; *Lymphopenia/diagnosis/etiology ; *Pleural Effusion/diagnosis/etiology ; *Anemia ; *Thrombocytopenia ; }, abstract = {The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect a number of human systems, including the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. These symptoms persist long after the acute infection has healed and is called "long COVID". Interestingly, there have been a series of reports that SARS-CoV-2 infections trigger the development of various autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory arthritis, myositis, vasculitis. Here, we report a novel case of SLE characterized by persistent pleural effusion and lymphopenia following SARS-CoV-2 infection. This is the first case in the Western Pacific region to our knowledge. Furthermore, we reviewed 10 similar cases including our case. By looking at the characteristics of each case, we found that serositis and lymphopenia are common features of SLE following SARS-CoV-2 infection. Our finding suggests that patients with prolonged pleural effusion and/or lymphopenia after COVID-19 should be checked for autoantibodies.}, } @article {pmid37286535, year = {2023}, author = {Chen, P and Wu, M and He, Y and Jiang, B and He, ML}, title = {Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {237}, pmid = {37286535}, issn = {2059-3635}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Lipid Metabolism ; }, abstract = {The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.}, } @article {pmid37286327, year = {2023}, author = {Walker, S and Goodfellow, H and Pookarnjanamorakot, P and Murray, E and Bindman, J and Blandford, A and Bradbury, K and Cooper, B and Hamilton, FL and Hurst, JR and Hylton, H and Linke, S and Pfeffer, P and Ricketts, W and Robson, C and Stevenson, FA and Sunkersing, D and Wang, J and Gomes, M and Henley, W and Collaboration, LWCR}, title = {Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study.}, journal = {BMJ open}, volume = {13}, number = {6}, pages = {e069217}, pmid = {37286327}, issn = {2044-6055}, support = {NIHR132243/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Activities of Daily Living ; *COVID-19/complications ; Cross-Sectional Studies ; Fatigue/etiology ; Post-Acute COVID-19 Syndrome ; *Quality of Life ; Adolescent ; Young Adult ; Aged ; }, abstract = {OBJECTIVES: To describe self-reported characteristics and symptoms of treatment-seeking patients with post-COVID-19 syndrome (PCS). To assess the impact of symptoms on health-related quality of life (HRQoL) and patients' ability to work and undertake activities of daily living.

DESIGN: Cross-sectional single-arm service evaluation of real-time user data.

SETTING: 31 post-COVID-19 clinics in the UK.

PARTICIPANTS: 3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation.

INTERVENTION: Patients using the Living With Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022.

The primary outcome was the baseline Work and Social Adjustment Scale (WSAS). WSAS measures the functional limitations of the patient; scores of ≥20 indicate moderately severe limitations. Other symptoms explored included fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), depression (Patient Health Questionnaire-Eight Item Depression Scale), anxiety (Generalised Anxiety Disorder Scale, Seven-Item), breathlessness (Medical Research Council Dyspnoea Scale and Dyspnoea-12), cognitive impairment (Perceived Deficits Questionnaire, Five-Item Version) and HRQoL (EQ-5D). Symptoms and demographic characteristics associated with more severe functional limitations were identified using logistic regression analysis.

RESULTS: 3541 (94%) patients were of working age (18-65); mean age (SD) 48 (12) years; 1282 (71%) were female and 89% were white. 51% reported losing ≥1 days from work in the previous 4 weeks; 20% reported being unable to work at all. Mean WSAS score at baseline was 21 (SD 10) with 53% scoring ≥20. Factors associated with WSAS scores of ≥20 were high levels of fatigue, depression and cognitive impairment. Fatigue was found to be the main symptom contributing to a high WSAS score.

CONCLUSION: A high proportion of this PCS treatment-seeking population was of working age with over half reporting moderately severe or worse functional limitation. There were substantial impacts on ability to work and activities of daily living in people with PCS. Clinical care and rehabilitation should address the management of fatigue as the dominant symptom explaining variation in functionality.}, } @article {pmid37283936, year = {2023}, author = {Margeta, M}, title = {Neuromuscular disease: 2023 update.}, journal = {Free neuropathology}, volume = {4}, number = {}, pages = {}, pmid = {37283936}, issn = {2699-4445}, abstract = {This review highlights ten important advances in the neuromuscular disease field that were reported in 2022. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 and 2022 reviews), DNAJB4-associated myopathy, NMNAT2-deficient hereditary axonal neuropathy, Guillain-Barré syndrome, sporadic inclusion body myositis, and amyotrophic lateral sclerosis. In addition, the review highlights a few other advances (including new insights into mechanisms of fiber maturation during muscle regeneration and fiber rebuilding following reinnervation, improved genetic testing methods for facioscapulohumeral and myotonic muscular dystrophies, and the use of SARM1 inhibitors to block Wallerian degeneration) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.}, } @article {pmid37283920, year = {2023}, author = {Maffia-Bizzozero, S and Cevallos, C and Lenicov, FR and Freiberger, RN and Lopez, CAM and Guano Toaquiza, A and Sviercz, F and Jarmoluk, P and Bustos, C and D'Addario, AC and Quarleri, J and Delpino, MV}, title = {Viable SARS-CoV-2 Omicron sub-variants isolated from autopsy tissues.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1192832}, pmid = {37283920}, issn = {1664-302X}, abstract = {INTRODUCTION: Pulmonary and extrapulmonary manifestations have been described after infection with SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The virus is known to persist in multiple organs due to its tropism for several tissues. However, previous reports were unable to provide definitive information about whether the virus is viable and transmissible. It has been hypothesized that the persisting reservoirs of SARS-CoV-2 in tissues could be one of the multiple potentially overlapping causes of long COVID.

METHODS: In the present study, we investigated autopsy materials obtained from 21 cadaveric donors with documented first infection or reinfection at the time of death. The cases studied included recipients of different formulations of COVID-19 vaccines. The aim was to find the presence of SARS-CoV-2 in the lungs, heart, liver, kidneys, and intestines. We used two technical approaches: the detection and quantification of viral genomic RNA using RT-qPCR, and virus infectivity using permissive in vitro Vero E6 culture.

RESULTS: All tissues analyzed showed the presence of SARS-CoV-2 genomic RNA but at dissimilar levels ranging from 1.01 × 10[2] copies/mL to 1.14 × 10[8] copies/mL, even among those cases who had been COVID-19 vaccinated. Importantly, different amounts of replication-competent virus were detected in the culture media from the studied tissues. The highest viral load were measured in the lung (≈1.4 × 10[6] copies/mL) and heart (≈1.9 × 10[6] copies/mL) samples. Additionally, based on partial Spike gene sequences, SARS-CoV-2 characterization revealed the presence of multiple Omicron sub-variants exhibiting a high level of nucleotide and amino acid identity among them.

DISCUSSION: These findings highlight that SARS-CoV-2 can spread to multiple tissue locations such as the lungs, heart, liver, kidneys, and intestines, both after primary infection and after reinfections with the Omicron variant, contributing to extending knowledge about the pathogenesis of acute infection and understanding the sequelae of clinical manifestations that are observed during post-acute COVID-19.}, } @article {pmid37283183, year = {2023}, author = {Cruess, SM and Callahan, JX and Raso, I and Valencia, B and Eskander, J}, title = {Icosapent ethyl (VASCEPA[®]) as treatment for post-acute sequelae of SARS CoV-2 (PASC) vaccine induced injury and infection.}, journal = {Journal of complementary & integrative medicine}, volume = {20}, number = {3}, pages = {662-664}, pmid = {37283183}, issn = {1553-3840}, mesh = {Humans ; Adult ; *COVID-19 Vaccines ; *COVID-19 ; Pandemics ; Eicosapentaenoic Acid/pharmacology/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: As the COVID-19 pandemic continues, a prolonged post-infectious syndrome or "long COVID" has been reported. This is a multi-organ post viral syndrome that persists well after infection. Currently, there is no available treatment. Emerging evidence credits this "long COVID" syndrome to ongoing inflammatory response following resolution of symptoms during infection. An omega-three fatty acid derivative used in the treatment of hypertriglyceridemia, Icosapent Ethyl (IPE, VASCEPA[®]/Epadel[®]), was previously shown to reduce cardiovascular risk, likely via immunomodulatory effects. This study aims to evaluate the effectiveness of Icosapent Ethyl.

METHODS: Following previous publications in treatment of severe acute COVID-19, we analyze two case studies of adults treated with Icosapent Ethyl.

RESULTS: After experiencing the symptoms of Long Covid, both individuals analyzed across two case studies experiences a resolution of symptoms after treatment with Icosapent Ethyl.

CONCLUSION: After review and analysis we conclude that Icosapent Ethyl may have been a determining factor in Long COVID symptom resolution and should be studied further.}, } @article {pmid37282564, year = {2023}, author = {Rømer, V and Sivapalan, P and Eklöf, J and Nielsen, SD and Harboe, ZB and Biering-Sørensen, T and Itenov, T and Jensen, JS}, title = {SARS-CoV-2 and risk of psychiatric hospital admission and use of psychopharmaceuticals: A nationwide registry study of 4,585,083 adult Danish citizens.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {66}, number = {1}, pages = {e50}, pmid = {37282564}, issn = {1778-3585}, mesh = {Humans ; Adult ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Hospitals, Psychiatric ; Psychotropic Drugs/adverse effects ; Registries ; Denmark/epidemiology ; }, abstract = {BACKGROUND: Current evidence on the risk of admission- or medication-requiring psychiatric sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited to selected populations, short durations, and loss to follow-up. This study examined if SARS-CoV-2 infection was associated with increased long-term risk of psychiatric admissions and de novo prescription of psychoactive medication in the general population of Denmark.

METHODS: Adults (≥18 years) were assigned to either the control or SARS-CoV-2 group based on polymerase chain reaction (PCR) tests between 1 January 2020 and 27 November 2021. Infected subjects were matched 1:5 to control subjects by propensity score. Incidence rate ratios (IRRs) were calculated. Adjusted Cox regression was applied to the unmatched population with SARS-CoV-2 infection as a time-dependent covariate. Follow-up time was 12 months or until the end of the study.

RESULTS: A total of 4,585,083 adults were included in the study. Approximately 342,084 had a PCR-confirmed SARS-CoV-2 infection and were matched 1:5 with 1,697,680 controls. The IRR for psychiatric admission was 0.79 in the matched population (95% confidence interval [CI]: 0.73-0.85, p < 0.001). In the unmatched population, the adjusted hazard ratios (aHR) for psychiatric admission were either below 1.00 or with a 95% CI lower limit of 1.01. SARS-CoV-2 infection was associated with an increased risk of de novo prescription of psychoactive medication in both the matched (IRR 1.06, 95% CI: 1.02-1.11, p < 0.01) and unmatched population (HR 1.31, 95% CI: 1.28-1.34, p < 0.001).

CONCLUSIONS: We found a signal of increased use of psychoactive medication, specifically benzodiazepines, among SARS-CoV-2-positive persons, but the risk of psychiatric admissions did not increase.}, } @article {pmid37282346, year = {2023}, author = {Israel, A and Berkovitch, M and Merzon, E and Golan-Cohen, A and Green, I and Ruppin, E and Vinker, S and Magen, E}, title = {Glucose-6-Phosphate Dehydrogenase Deficiency and Coronavirus Disease 2019.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {7}, pages = {972-975}, pmid = {37282346}, issn = {1537-6591}, mesh = {Humans ; Cohort Studies ; *COVID-19/genetics ; *Glucosephosphate Dehydrogenase/genetics ; *Glucosephosphate Dehydrogenase Deficiency/complications/epidemiology/diagnosis ; Israel/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {In this cohort study conducted in a national healthcare organization in Israel, we found that individuals with glucose-6-phosphate dehydrogenase deficiency had an increased risk of coronavirus disease 2019 (COVID-19) infection and severity, with higher rates of hospitalization and diagnosed long COVID.}, } @article {pmid37280412, year = {2023}, author = {Engels, G and Oechsle, AL and Schlegtendal, A and Maier, C and Holzwarth, S and Streng, A and Lange, B and Karch, A and Petersmann, A and Streeck, H and Blaschke-Steinbrecher, S and Härtel, C and Schroten, H and von Kries, R and Berner, R and Liese, J and Brinkmann, F and Toepfner, N and , }, title = {SARS-CoV-2 sero-immunity and quality of life in children and adolescents in relation to infections and vaccinations: the IMMUNEBRIDGE KIDS cross-sectional study, 2022.}, journal = {Infection}, volume = {51}, number = {5}, pages = {1531-1539}, pmid = {37280412}, issn = {1439-0973}, support = {01KX2121//Bundesministerium für Bildung und Forschung/ ; paedSaxCoviDD//Freistaat Sachsen/ ; K3-2484-PN 22-38-V3-D28504/2022//Bavarian State Ministry of Health and Care and the Bavarian Health and Food Safety Authority/ ; }, mesh = {Adolescent ; Child ; Humans ; Child, Preschool ; *Quality of Life ; SARS-CoV-2 ; Cross-Sectional Studies ; *COVID-19/epidemiology/prevention & control ; Seroepidemiologic Studies ; Antibodies, Viral ; Vaccination ; }, abstract = {PURPOSE: The study evaluates the effects on sero-immunity, health status and quality of life of children and adolescents after the upsurge of the Omicron variant in Germany.

METHODS: This multicenter cross-sectional study (IMMUNEBRIDGE Kids) was conducted within the German Network University Medicine (NUM) from July to October 2022. SARS-CoV-2- antibodies were measured and data on SARS-CoV-2 infections, vaccinations, health and socioeconomic factors as well as caregiver-reported evaluation on their children's health and psychological status were assessed.

RESULTS: 497 children aged 2-17 years were included. Three groups were analyzed: 183 pre-schoolchildren aged 2-4 years, 176 schoolchildren aged 5-11 years and 138 adolescents aged 12-18 years. Positive antibodies against the S- or N-antigen of SARS-CoV-2 were detected in 86.5% of all participants (70.0% [128/183] of pre-schoolchildren, 94.3% of schoolchildren [166/176] and 98.6% of adolescents [136/138]). Among all children, 40.4% (201/497) were vaccinated against COVID-19 (pre-schoolchildren 4.4% [8/183], schoolchildren 44.3% [78/176] and adolescents 83.3% [115/138]). SARS-CoV-2 seroprevalence was lowest in pre-school. Health status and quality of life reported by the parents were very positive at the time of the survey (Summer 2022).

CONCLUSION: Age-related differences on SARS-CoV-2 sero-immunity could mainly be explained by differences in vaccination rates based on the official German vaccination recommendations as well as differences in SARS-CoV-2 infection rates in the different age groups. Health status and quality of life of almost all children were very good independent of SARS-CoV-2 infection and/or vaccination.

TRIAL REGISTRATION: German Registry for Clinical Trials Identifier Würzburg: DRKS00025546 (registration: 11.09.2021), Bochum: DRKS00022434 (registration:07.08.2020), Dresden: DRKS 00022455 (registration: 23.07.2020).}, } @article {pmid37279939, year = {2023}, author = {Bikle, DD}, title = {Vitamin D and Long COVID: Is There a Role in Prevention or Treatment?.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {109}, number = {1}, pages = {e430-e431}, doi = {10.1210/clinem/dgad338}, pmid = {37279939}, issn = {1945-7197}, mesh = {Humans ; *Vitamin D/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Vitamins/therapeutic use ; Immunity, Innate ; }, } @article {pmid37278994, year = {2023}, author = {Thaweethai, T and Jolley, SE and Karlson, EW and Levitan, EB and Levy, B and McComsey, GA and McCorkell, L and Nadkarni, GN and Parthasarathy, S and Singh, U and Walker, TA and Selvaggi, CA and Shinnick, DJ and Schulte, CCM and Atchley-Challenner, R and Alba, GA and Alicic, R and Altman, N and Anglin, K and Argueta, U and Ashktorab, H and Baslet, G and Bassett, IV and Bateman, L and Bedi, B and Bhattacharyya, S and Bind, MA and Blomkalns, AL and Bonilla, H and Brim, H and Bush, PA and Castro, M and Chan, J and Charney, AW and Chen, P and Chibnik, LB and Chu, HY and Clifton, RG and Costantine, MM and Cribbs, SK and Davila Nieves, SI and Deeks, SG and Duven, A and Emery, IF and Erdmann, N and Erlandson, KM and Ernst, KC and Farah-Abraham, R and Farner, CE and Feuerriegel, EM and Fleurimont, J and Fonseca, V and Franko, N and Gainer, V and Gander, JC and Gardner, EM and Geng, LN and Gibson, KS and Go, M and Goldman, JD and Grebe, H and Greenway, FL and Habli, M and Hafner, J and Han, JE and Hanson, KA and Heath, J and Hernandez, C and Hess, R and Hodder, SL and Hoffman, MK and Hoover, SE and Huang, B and Hughes, BL and Jagannathan, P and John, J and Jordan, MR and Katz, SD and Kaufman, ES and Kelly, JD and Kelly, SW and Kemp, MM and Kirwan, JP and Klein, JD and Knox, KS and Krishnan, JA and Kumar, A and Laiyemo, AO and Lambert, AA and Lanca, M and Lee-Iannotti, JK and Logarbo, BP and Longo, MT and Luciano, CA and Lutrick, K and Maley, JH and Mallett, G and Marathe, JG and Marconi, V and Marshall, GD and Martin, CF and Matusov, Y and Mehari, A and Mendez-Figueroa, H and Mermelstein, R and Metz, TD and Morse, R and Mosier, J and Mouchati, C and Mullington, J and Murphy, SN and Neuman, RB and Nikolich, JZ and Ofotokun, I and Ojemakinde, E and Palatnik, A and Palomares, K and Parimon, T and Parry, S and Patterson, JE and Patterson, TF and Patzer, RE and Peluso, MJ and Pemu, P and Pettker, CM and Plunkett, BA and Pogreba-Brown, K and Poppas, A and Quigley, JG and Reddy, U and Reece, R and Reeder, H and Reeves, WB and Reiman, EM and Rischard, F and Rosand, J and Rouse, DJ and Ruff, A and Saade, G and Sandoval, GJ and Santana, JL and Schlater, SM and Sciurba, FC and Shepherd, F and Sherif, ZA and Simhan, H and Singer, NG and Skupski, DW and Sowles, A and Sparks, JA and Sukhera, FI and Taylor, BS and Teunis, L and Thomas, RJ and Thorp, JM and Thuluvath, P and Ticotsky, A and Tita, AT and Tuttle, KR and Urdaneta, AE and Valdivieso, D and VanWagoner, TM and Vasey, A and Verduzco-Gutierrez, M and Wallace, ZS and Ward, HD and Warren, DE and Weiner, SJ and Welch, S and Whiteheart, SW and Wiley, Z and Wisnivesky, JP and Yee, LM and Zisis, S and Horwitz, LI and Foulkes, AS and , }, title = {Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.}, journal = {JAMA}, volume = {329}, number = {22}, pages = {1934-1946}, pmid = {37278994}, issn = {1538-3598}, support = {OT2 HL156812/HL/NHLBI NIH HHS/United States ; UG1 HD027869/HD/NICHD NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; UG1 HD040544/HD/NICHD NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; UG1 HD040500/HD/NICHD NIH HHS/United States ; R01 HL162373/HL/NHLBI NIH HHS/United States ; R01 DK130351/DK/NIDDK NIH HHS/United States ; P30 AG072946/AG/NIA NIH HHS/United States ; U10 HD040500/HD/NICHD NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UG1 HD087230/HD/NICHD NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; UG1 HD087192/HD/NICHD NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 HL161386/HL/NHLBI NIH HHS/United States ; }, mesh = {Female ; Adult ; Humans ; Middle Aged ; Male ; *SARS-CoV-2 ; *COVID-19/complications ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Disease Progression ; Fatigue ; }, abstract = {IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.

OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.

Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds).

RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.

CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.}, } @article {pmid37277879, year = {2023}, author = {Boles, S and Ashok, SR}, title = {Pre-assessment and management of long COVID patients requiring elective surgery: challenges and guidance.}, journal = {Perioperative medicine (London, England)}, volume = {12}, number = {1}, pages = {20}, pmid = {37277879}, issn = {2047-0525}, abstract = {Whilst most patients infected with COVID-19 make a full recovery, around 1 in 33 patients in the UK report ongoing symptoms post-infection, termed 'long COVID'. Studies have demonstrated that infection with early COVID-19 variants increases postoperative mortality and pulmonary complications for around 7 weeks after acute infection. Furthermore, this increased risk persists for those with ongoing symptoms beyond 7 weeks. Patients with long COVID may therefore also be at increased postoperative risk, and despite the significant prevalence of long COVID, there are minimal guidelines on how best to assess and manage these patients perioperatively. Long COVID shares several clinical and pathophysiological similarities with conditions such as myalgic encephalitis/chronic fatigue syndrome and postural tachycardia syndrome; however, there are no current guidelines for the preoperative management of these patients to help develop something similar for long COVID patients. Developing guidelines for long COVID patients is further complicated by its heterogenous presentation and pathology. These patients can have persistent abnormalities on pulmonary function tests and echocardiography 3 months after acute infection, correlating with a reduced functional capacity. Conversely, some long COVID patients can continue to experience symptoms of dyspnoea and fatigue despite normal pulmonary function tests and echocardiography, yet demonstrating significantly reduced aerobic capacity on cardiopulmonary exercise testing even a year after initial infection. How to comprehensively risk assess these patients is therefore challenging. Existing preoperative guidelines for elective patients with recent COVID-19 generally focus on the timing of surgery and recommendations for pre-assessment if surgery is required before this time interval has elapsed. How long to delay surgery in those with ongoing symptoms and how to manage them perioperatively are less clear. We suggest that multidisciplinary decision-making is required for these patients, using a systems-based approach to guide discussion with specialists and the need for further preoperative investigations. However, without a better understanding of the postoperative risks for long COVID patients, it is difficult to obtain a multidisciplinary consensus and obtain informed patient consent. Prospective studies of long COVID patients undergoing elective surgery are urgently required to help quantify their postoperative risk and develop comprehensive perioperative guidelines for this complex patient group.}, } @article {pmid37277786, year = {2023}, author = {Cox, SN and Scott, EM and Rogers, JH and Chow, EJ and Wasse, JK and Carone, M and Hughes, JP and Chu, HY}, title = {Burden of long COVID among adults experiencing sheltered homelessness: a longitudinal cohort study in King County, WA between September 2020-April 2022.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {1079}, pmid = {37277786}, issn = {1471-2458}, support = {T32 AI007044/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Adult ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Prospective Studies ; *Ill-Housed Persons ; }, abstract = {BACKGROUND: People experiencing homelessness (PEH) are at increased risk for acquiring SARS-CoV-2, but the burden of long COVID in this population is unknown.

METHODS: We conducted a matched prospective cohort study to assess the prevalence, characteristics, and impact of long COVID among sheltered PEH in Seattle, WA between September 2020-April 2022. Adults ≥ 18 years, residing across nine homeless shelters with active respiratory virus surveillance, were eligible to complete in-person baseline surveys and interval follow-up phone surveys. We included a subset of 22 COVID-19-positive cases who tested positive or inconclusive for SARS-CoV-2 and 44 COVID-19-negative controls who tested negative for SARS-CoV-2, frequency matched on age and sex. Among controls, 22 were positive and 22 were negative for one of 27 other respiratory virus pathogens. To assess the impact of COVID-19 on the risk of symptom presence at follow-up (day 30-225 post-enrollment test), we performed log-linear regression with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori.

RESULTS: Of 53 eligible COVID-19 cases, 22 (42%) completed ≥ 1 follow-up survey. While five (23%) cases reported ≥ 1 symptom at baseline, this increased to 77% (10/13) between day 30-59 and 33% (4/12) day 90 + . The most commonly reported symptoms day 30 + were fatigue (27%) and rhinorrhea (27%), with 8 (36%) reporting symptoms that interfered with or prevented daily activities. Four (33%) symptomatic cases reported receiving medical care outside of a medical provider at an isolation facility. Of 44 controls, 12 (27%) reported any symptoms day 90 + . Risk of any symptoms at follow-up was 5.4 times higher among COVID-19 cases compared to controls (95% CI: 2.7-10.5).

CONCLUSIONS: Shelter residents reported a high prevalence of symptoms 30 + days after their SARS-CoV-2 detection, though few accessed medical care for persistent illness. The impact of COVID-19 extends beyond acute illness and may exacerbate existing challenges that marginalized populations face in maintaining their health and wellbeing.}, } @article {pmid37277617, year = {2023}, author = {Kuck, KH and Schlüter, M and Vogler, J and Heeger, CH and Tilz, RR}, title = {Has COVID-19 changed the spectrum of arrhythmias and the incidence of sudden cardiac death?.}, journal = {Herz}, volume = {48}, number = {3}, pages = {212-217}, pmid = {37277617}, issn = {1615-6692}, mesh = {Humans ; *Atrial Fibrillation ; Incidence ; Post-Acute COVID-19 Syndrome ; Hospital Mortality ; *COVID-19 ; SARS-CoV-2 ; Death, Sudden, Cardiac/epidemiology/etiology/prevention & control ; }, abstract = {Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. In view of new SARS-CoV‑2 variants that may evolve, the development and use of newer antiviral and immunomodulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.}, } @article {pmid37275716, year = {2023}, author = {Rapelli, G and Varallo, G and Scarpelli, S and Pietrabissa, G and Musetti, A and Plazzi, G and Franceschini, C and Castelnuovo, G}, title = {The long wave of COVID-19: a case report using Imagery Rehearsal Therapy for COVID-19-related nightmares after admission to intensive care unit.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1144087}, pmid = {37275716}, issn = {1664-1078}, abstract = {INTRODUCTION: The COVID-19 pandemic caused several psychological consequences for the general population. In particular, long-term and persistent psychopathological detriments were observed in those who were infected by acute forms of the virus and need specialistic care in the Intensive Care Unit (ICU). Imagery rehearsal therapy (IRT) has shown promising results in managing nightmares of patients with different traumas, but it has never been used with patients admitted to ICUs for severe COVID-19 despite this experience being considered traumatic in the literature.

METHODS: The purpose of this case study is to describe the application of a four-session IRT for the treatment of COVID-related nightmares in a female patient after admission to the ICU. A 42-year-old Caucasian woman who recovered from a pulmonary rehabilitation program reported shortness of breath, dyspnea, and everyday life difficulties triggered by the long-COVID syndrome. She showed COVID-related nightmares and signs of post-traumatic symptoms (i.e., hyperarousal, nightmares, and avoidance of triggers associated with the traumatic situation). Psychological changes in the aftermath of a trauma, presence, and intensity of daytime sleepiness, dream activity, sleep disturbances, aspects of sleep and dreams, and symptoms of common mental health status are assessed as outcomes at the baseline (during the admission to pneumology rehabilitation) at 1-month (T1) and 3-month follow-up (T2). Follow-up data were collected through an online survey.

RESULTS: By using IRT principles and techniques, the patient reported a decrease in the intensity and frequency of bad nightmares, an increase in the quality of sleep, and post-traumatic growth, developing a positive post-discharge.

CONCLUSION: Imagery rehearsal therapy may be effective for COVID-19-related nightmares and in increasing the quality of sleep among patients admitted to the ICU for the treatment of COVID-19. Furthermore, IRT could be useful for its brevity in hospital settings.}, } @article {pmid37275532, year = {2023}, author = {Oka, N and Shimada, K and Ishii, A and Kobayashi, N and Kondo, K}, title = {SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production.}, journal = {iScience}, volume = {26}, number = {6}, pages = {106954}, pmid = {37275532}, issn = {2589-0042}, abstract = {Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute to long COVID. However, in autopsies of patients who have died from COVID-19, there is normally no direct evidence that central nervous system damage is due to proliferation of SARS-CoV-2. For this reason, many aspects of the pathogenesis mechanisms of such symptoms remain unknown. Expressing SARS-CoV-2 S1 protein in the nasal cavity of mice was associated with increased apoptosis of the olfactory system and decreased intracerebral acetylcholine production. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and decreased expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise and depressive clinical signs. These findings could contribute to the elucidation of the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.}, } @article {pmid37274795, year = {2023}, author = {Chancharoenthana, W and Kamolratanakul, S and Leelahavanichkul, A and Ariyanon, W and Chinpraditsuk, S and Saelim, R and Vadcharavivad, S and Phumratanaprapin, W and Wilairatana, P}, title = {Gastrointestinal manifestations of long-term effects after COVID-19 infection in patients with dialysis or kidney transplantation: An observational cohort study.}, journal = {World journal of gastroenterology}, volume = {29}, number = {19}, pages = {3013-3026}, pmid = {37274795}, issn = {2219-2840}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Male ; Renal Dialysis/adverse effects ; *Kidney Transplantation/adverse effects ; *Kidney Failure, Chronic/epidemiology/therapy ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cohort Studies ; *Gastrointestinal Diseases/diagnosis/epidemiology/etiology ; }, abstract = {BACKGROUND: Prolonged symptoms after corona virus disease 2019 (Long-COVID) in dialysis-dependent patients and kidney transplant (KT) recipients are important as a possible risk factor for organ dysfunctions, especially gastrointestinal (GI) problems, during immunosuppressive therapy.

AIM: To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.

METHODS: This observational, prospective study included patients with COVID-19 infection, confirmed by reverse transcription polymerase chain reaction, with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset, either through the out-patient follow-up or by telephone interviews.

RESULTS: The 645 eligible participants consisted of 588 cases with hemodialysis (HD), 38 patients with peritoneal dialysis (PD), and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these, 577 (89.5%) cases agreed to the interviews, while 64 (10.9%) patients with HD and 4 (10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups, respectively, and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524 (56%) and 21/34 (62%) in HD and PD, respectively, and 7/19 (37%) KT recipients. Fatigue was the most prevalent (96%) of the non-GI tract symptoms, whereas anorexia (90.9%), loss of taste (64.4%), and abdominal pain (62.5%) were the first three common GI manifestations of Long-COVID. Notably, there were 6 cases of mesenteric panniculitis from 19 patients with GI symptoms in the KT group.

CONCLUSION: Different from patients with non-chronic kidney disease, there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.}, } @article {pmid37274652, year = {2023}, author = {García-Dolores, F and Tendilla-Beltrán, H and Flores, F and Carbajal-Rimoldi, LA and Mendoza-Morales, RC and Gómez-Mendoza, LE and Vázquez-Hernández, AJ and de la Cruz, F and Genis-Mendoza, AD and Nicolini, H and Flores, G}, title = {Increased suicide rates in Mexico City during the COVID-19 pandemic outbreak: An analysis spanning from 2016 to 2021.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16420}, pmid = {37274652}, issn = {2405-8440}, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) has impacted mental health worldwide, and suicide can be a serious outcome of this. Thus, suicide characteristics were examined before and during the COVID-19 pandemic in Mexico City.

METHODS: This is a retrospective study including all Mexico City residents who had a coroner's record with a cause of death of intentional self-harm (ICD-10) from January 2016 to December 2021.

RESULTS: From 2016 to 2021, 3636 people committed suicide, of which 2869 were males (78.9%) and 767 females (21.1%). From 2016 to 2019 the suicide rate remained constant (∼6 per 100000) and dramatically increased in 2020 (10.45 per 100,000), to return to the levels of the previous year in 2021 (6.95 per 100000). The suicide rate in 2020 specifically increased from January to June (COVID-19 outbreak) in all age groups. Moreover, every year young people (15-24 years) have the maximum suicide rate and depression was the main suicide etiology.

CONCLUSION: The COVID-19 pandemic outbreak increased the suicide rate, regardless of age, but suicide prevalence was higher in males and young people, regardless of the COVID-19 pandemic. These findings confirm that suicide is a complex and multifactorial problem and will allow the establishment of new guidelines for prevention and care strategies.}, } @article {pmid37272533, year = {2023}, author = {Dorfman, D and Berger, Z}, title = {Approving Workplace Accommodations for Patients with Long Covid - Advice for Clinicians.}, journal = {The New England journal of medicine}, volume = {388}, number = {23}, pages = {2115-2117}, doi = {10.1056/NEJMp2302676}, pmid = {37272533}, issn = {1533-4406}, mesh = {Humans ; COVID-19 ; *Disabled Persons ; Employment ; *Post-Acute COVID-19 Syndrome/complications ; *Working Conditions ; *Workplace ; }, } @article {pmid37272468, year = {2023}, author = {Marra, AR and Sampaio, VS and Ozahata, MC and Lopes, R and Brito, AF and Bragatte, M and Kalil, J and Miraglia, JL and Malheiro, DT and Guozhang, Y and Teich, VD and Victor, EDS and Pinho, JRR and Cypriano, A and Vieira, LW and Polonio, M and de Oliveira, SM and Ricardo, VCV and Maezato, AM and Callado, GY and Schettino, GPP and de Oliveira, KG and Santana, RAF and Malta, FM and Amgarten, D and Boechat, AL and Kobayashi, T and Perencevich, E and Edmond, MB and Rizzo, LV}, title = {Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022.}, journal = {Infection control and hospital epidemiology}, volume = {44}, number = {12}, pages = {1972-1978}, pmid = {37272468}, issn = {1559-6834}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brazil/epidemiology ; COVID-19 Vaccines ; Case-Control Studies ; Risk Factors ; }, abstract = {OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP).

METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up.

RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID.

CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.}, } @article {pmid37272336, year = {2023}, author = {Cai, J and Lin, K and Zhang, H and Xue, Q and Zhu, K and Yuan, G and Sun, Y and Zhu, F and Ai, J and Wang, S and Zhang, W}, title = {A one-year follow-up study of systematic impact of long COVID symptoms among patients post SARS-CoV-2 omicron variants infection in Shanghai, China.}, journal = {Emerging microbes & infections}, volume = {12}, number = {2}, pages = {2220578}, pmid = {37272336}, issn = {2222-1751}, mesh = {Female ; Middle Aged ; Adolescent ; Humans ; Adult ; China/epidemiology ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Follow-Up Studies ; Quality of Life ; *COVID-19/epidemiology ; Outpatients ; }, abstract = {Long COVID hinders people from normal life and work, posing significant medical and economic challenges. Nevertheless, comprehensive studies assessing its impact on large populations in Asia are still lacking. We tracked over 20,000 patients infected with COVID-19 for the first time during the Omicron BA.2 outbreak in Shanghai from March-June 2022 for one year. Of the 21,799 COVID-19 patients who participated in the 6-month telephone follow-up, 1939 (8.89%) had self-reported long COVID symptoms. 450 long COVID patients participated in the 6-month outpatient follow-up. Participants underwent healthy physical examinations and questionnaires focused on long-COVID-related symptoms and mental health. Mobility problem (P < 0.001), personal care problem (P = 0.003), usual activity problem (P < 0.001), pain/discomfort (P < 0.001), anxiety/depression (P = 0.001) and PTSD (P = 0.001) were more prevalent in long COVID patients than in healthy individuals, but no significant differences were found between the two groups on chest CT and laboratory examinations. Of the 856 long COVID patients who participated in the 12-month follow-up, 587 (68.5%) had their symptoms resolved. In the multivariable logistic analysis, females (P < 0.001), youth (age <40 years) (P < 0.001), ≥ 2 comorbidities (P = 0.009), and severe infection in the acute phase (P = 0.006) were risk factors for developing long COVID. Middle age (40-60 years) was a risk factor for persistent long COVID one year after hospital discharge (P = 0.013). The study found that long COVID mainly manifested as subjective symptoms and impacts partial patients' quality of life and mental status. After one year, most (68.5%) of the patients recovered from long COVID with no impairment of organ function observed.}, } @article {pmid37271020, year = {2023}, author = {Romanet, C and Wormser, J and Fels, A and Lucas, P and Prudat, C and Sacco, E and Bruel, C and Plantefève, G and Pene, F and Chatellier, G and Philippart, F}, title = {Effectiveness of exercise training on the dyspnoea of individuals with long COVID: A randomised controlled multicentre trial.}, journal = {Annals of physical and rehabilitation medicine}, volume = {66}, number = {5}, pages = {101765}, pmid = {37271020}, issn = {1877-0665}, mesh = {Adult ; Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Dyspnea/therapy/rehabilitation ; *Respiratory Distress Syndrome ; Exercise ; Treatment Outcome ; }, abstract = {BACKGROUND: COVID-19-related acute respiratory distress syndrome (CARDS) is a severe evolution of the Sars-Cov-2 infection and necessitates intensive care. COVID-19 may subsequently be associated with long COVID, whose symptoms can include persistent respiratory symptoms up to 1 year later. Rehabilitation is currently recommended by most guidelines for people with this condition.

OBJECTIVES: To evaluate the effects of exercise training rehabilitation (ETR) on dyspnoea and health-related quality of life measures in people with continuing respiratory discomfort following CARDS.

METHODS: In this multicentre, two-arm, parallel, open, assessor-blinded, randomised controlled trial, we enroled adults previously admitted with CARDS to 3 French intensive care units who had been discharged at least 3 months earlier and who presented with an mMRC dyspnoea scale score > 1. Participants received either ETR or standard physiotherapy (SP) for 90 days. The primary outcome was dyspnoea, as measured by the Multidimensional Dyspnoea Profile (MDP), at day 0 (inclusion) and after 90 days of physiotherapy. Secondary outcomes were the mMRC and 12-item Short-Form Survey scores.

RESULTS: Between August 7, 2020, and January 26, 2022, 487 participants with CARDS were screened for inclusion, of whom 60 were randomly assigned to receive either ETR (n = 27) or SP (n = 33). Mean MDP following ETR was 42% lower than after SP (26.15 vs. 44.76); a difference of -18.61 (95% CI -27.78 to -9.44; p<10[-4]).

CONCLUSION: People who were still suffering from breathlessness three months after being discharged from hospital with CARDS had significantly improved dyspnoea scores when treated with ETR therapy for 90 days unlike those who only received SP. Study registered 29/09/2020 on Clinicaltrials.gov (NCT04569266).}, } @article {pmid37270195, year = {2023}, author = {Volckaerts, T and Vissers, D and Burtin, C and Van Meerbeeck, X and de Soomer, K and Oostveen, E and Claes, K and Roelant, E and Verhaegen, I and Thomeer, M and Criel, M and Quadflieg, K and Cops, D and Ruttens, D and Lapperre, TS}, title = {Randomised, controlled, open-label pragmatic trial evaluating changes in functional exercise capacity after primary care PUlmonary REhabilitation in patients with long COVID: protocol of the PuRe-COVID trial in Belgium.}, journal = {BMJ open}, volume = {13}, number = {6}, pages = {e071098}, pmid = {37270195}, issn = {2044-6055}, mesh = {Adult ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hand Strength ; Belgium ; Exercise Tolerance ; Prospective Studies ; Exercise ; Dyspnea/etiology/rehabilitation ; Primary Health Care ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Long COVID is a prevalent condition with many multisystemic symptoms, such as fatigue, dyspnoea, muscle weakness, anxiety, depression and sleep difficulties, impacting daily life and (social and physical) functioning. Pulmonary rehabilitation (PR) may improve physical status and symptoms of patients with long COVID, yet the evidence is limited. Therefore, this trial aims to study the effect of primary care PR on exercise capacity, symptoms, physical activity and sleep in patients with long COVID.

METHODS AND ANALYSIS: PuRe-COVID is a prospective, pragmatic, open-label, randomised controlled trial. A sample of 134 adult patients with long COVID will be randomised to a 12 week PR programme in primary care, supervised by a physiotherapist or to a control group, following no PR. A 3 month and 6 month follow-up period is foreseen. The primary endpoint will be the change in exercise capacity measured by 6-minute walk distance (6MWD) at 12 weeks, hypothesising a more significant improvement in the PR group. Other parameters, such as pulmonary function tests (including maximal inspiratory pressure/maximal expiratory pressure), patient-reported outcomes (COPD Assessment Test, modified Medical Research Council Dyspnoea Scale, Checklist Individual Strength, post-COVID-19 Functional Status, Nijmegen questionnaire, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment Questionnaire and EuroQol-5D-5L), physical activity measured by an activity tracker, hand grip strength and sleep efficiency, are secondary and exploratory outcomes.The recruitment started on 19 April 2022, and 52 patients were included as of 14 December 2022.

ETHICS AND DISSEMINATION: Ethical approval was obtained in Belgium from the relevant institutional review boards on 21 February 2022 (Antwerp University Hospital, approval number 2022-3067) and on 1 April 2022 (Ziekenhuis Oost-Limburg in Genk, approval number Z-2022-01). Findings from this randomised controlled trial will be disseminated in peer-reviewed publications and presentations at international scientific meetings.

TRIAL REGISTRATION NUMBER: NCT05244044.}, } @article {pmid37267758, year = {2023}, author = {Müller, S and Schultze, JL}, title = {Systems analysis of human innate immunity in COVID-19.}, journal = {Seminars in immunology}, volume = {68}, number = {}, pages = {101778}, pmid = {37267758}, issn = {1096-3618}, support = {GRK2168 – 272482170//German Research Foundation (/ ; 390873048//Excellence Cluster ImmunoSensation2, project/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Systems Analysis ; }, abstract = {Recent developments in sequencing technologies, the computer and data sciences, as well as increasingly high-throughput immunological measurements have made it possible to derive holistic views on pathophysiological processes of disease and treatment effects directly in humans. We and others have illustrated that incredibly predictive data for immune cell function can be generated by single cell multi-omics (SCMO) technologies and that these technologies are perfectly suited to dissect pathophysiological processes in a new disease such as COVID-19, triggered by SARS-CoV-2 infection. Systems level interrogation not only revealed the different disease endotypes, highlighted the differential dynamics in context of disease severity, and pointed towards global immune deviation across the different arms of the immune system, but was already instrumental to better define long COVID phenotypes, suggest promising biomarkers for disease and therapy outcome predictions and explains treatment responses for the widely used corticosteroids. As we identified SCMO to be the most informative technologies in the vest to better understand COVID-19, we propose to routinely include such single cell level analysis in all future clinical trials and cohorts addressing diseases with an immunological component.}, } @article {pmid37267521, year = {2023}, author = {Riepl, M and Kaiser, J}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 3: The Role of Toll-like Receptors in SARS-CoV-2 Infection and COVID Development.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {3}, pages = {192-200}, pmid = {37267521}, issn = {1092-4221}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Toll-Like Receptor 4 ; SARS-CoV-2 ; Toll-Like Receptors ; }, abstract = {Toll-like receptors, which are type I transmembrane proteins and pattern recognition receptors found on cell surfaces and in intracellular membranes, serve as central mediators of both initial innate-immune responses and secondary adaptive/acquired-immune responses. Toll-like receptor 4, the activation of which leads to the synthesis of proinflammatory cytokines and chemokines, has been shown to have a vital role in the innate immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In our practice of pharmaceutical compounding, we noted that some individuals with coronavirus disease- 2019 (COVID-19) or long COVID achieved limited or no benefit from commercially manufactured treatments designed to alleviate symptoms and enable recovery. We suggest that in such cases, a compounded formulation, which can be easily customized to provide that support, may be of benefit. This article provides a brief review of the ways in which toll-like receptors in general, and toll-like receptor 4 in particular, affect the development and progression of SARS-CoV-2 infection and COVID-19, especially with respect to the human respiratory and central nervous systems and people rendered vulnerable by a comorbid condition (diabetes, obesity) or age. Instructions for compounding 2 customized preparations useful in the treatment of COVID-19 and long COVID are also provided.}, } @article {pmid37267401, year = {2023}, author = {Soriano, JB and Peláez, A and Busquets, X and Rodrigo-García, M and Pérez-Urría, EÁ and Alonso, T and Girón, R and Valenzuela, C and Marcos, C and García-Castillo, E and Ancochea, J}, title = {ABO blood group as a determinant of COVID-19 and Long COVID: An observational, longitudinal, large study.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0286769}, pmid = {37267401}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; ABO Blood-Group System ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Longitudinal Studies ; Rh-Hr Blood-Group System ; }, abstract = {BACKGROUND: An association of ABO blood group and COVID-19 remains controversial.

METHODS: Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI).

RESULTS: Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID.

CONCLUSIONS: No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified.}, } @article {pmid37267379, year = {2023}, author = {Wong, AW and Tran, KC and Binka, M and Janjua, NZ and Sbihi, H and Russell, JA and Carlsten, C and Levin, A and Ryerson, CJ}, title = {Use of latent class analysis and patient reported outcome measures to identify distinct long COVID phenotypes: A longitudinal cohort study.}, journal = {PloS one}, volume = {18}, number = {6}, pages = {e0286588}, pmid = {37267379}, issn = {1932-6203}, support = {HEC 181075//CIHR/Canada ; }, mesh = {Female ; Humans ; Male ; *Quality of Life ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Latent Class Analysis ; *COVID-19 ; Dyspnea ; Patient Reported Outcome Measures ; Fatigue ; British Columbia ; }, abstract = {OBJECTIVES: We sought to 1) identify long COVID phenotypes based on patient reported outcome measures (PROMs) and 2) determine whether the phenotypes were associated with quality of life (QoL) and/or lung function.

METHODS: This was a longitudinal cohort study of hospitalized and non-hospitalized patients from March 2020 to January 2022 that was conducted across 4 Post-COVID Recovery Clinics in British Columbia, Canada. Latent class analysis was used to identify long COVID phenotypes using baseline PROMs (fatigue, dyspnea, cough, anxiety, depression, and post-traumatic stress disorder). We then explored the association between the phenotypes and QoL (using the EuroQoL 5 dimensions visual analogue scale [EQ5D VAS]) and lung function (using the diffusing capacity of the lung for carbon monoxide [DLCO]).

RESULTS: There were 1,344 patients enrolled in the study (mean age 51 ±15 years; 780 [58%] were females; 769 (57%) were of a non-White race). Three distinct long COVID phenotypes were identified: Class 1) fatigue and dyspnea, Class 2) anxiety and depression, and Class 3) fatigue, dyspnea, anxiety, and depression. Class 3 had a significantly lower EQ5D VAS at 3 (50±19) and 6 months (54 ± 22) compared to Classes 1 and 2 (p<0.001). The EQ5D VAS significantly improved between 3 and 6 months for Class 1 (median difference of 6.0 [95% CI, 4.0 to 8.0]) and Class 3 (median difference of 5.0 [95% CI, 0 to 8.5]). There were no differences in DLCO between the classes.

CONCLUSIONS: There were 3 distinct long COVID phenotypes with different outcomes in QoL between 3 and 6 months after symptom onset. These phenotypes suggest that long COVID is a heterogeneous condition with distinct subpopulations who may have different outcomes and warrant tailored therapeutic approaches.}, } @article {pmid37267198, year = {2023}, author = {Zhang, JX and Zhang, JJ}, title = {Case Report of Improvement in Long-COVID Symptoms in an Air Force Medic Treated With Transcranial Magnetic Stimulation Using Electro-Magnetic Brain Pulse Technique.}, journal = {Military medicine}, volume = {188}, number = {11-12}, pages = {e3711-e3715}, doi = {10.1093/milmed/usad182}, pmid = {37267198}, issn = {1930-613X}, mesh = {Male ; Humans ; Adult ; *Transcranial Magnetic Stimulation/methods ; Anosmia ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/therapy ; Brain/physiology ; Dyspnea/etiology/therapy ; Magnetic Phenomena ; }, abstract = {Long-coronavirus disease (COVID) is an ill-defined set of symptoms persisting in patients following infection with COVID-19 that range from any combination of persistent breathing difficulties to anosmia, impaired attention, memory, fatigue, or pain. Recently, noninvasive transcutaneous electrical brain stimulation techniques have been showing early signs of success in addressing some of these complaints. We postulate that the use of a stimulation technique with transcranial magnetic stimulation may also similarly be effective. A 36-year-old male suffering from symptoms of dyspnea, anosmia, and "brain fog" for 2 years following coronavirus infection was treated with 10 sessions of Electro-Magnetic Brain Pulse (EMBP®), a personalized transcranial magnetic stimulation protocol guided by the patient's electroencephalograph (EEG). At the conclusion of the treatment, the patient had improvements in mood, sense of smell, and brain fogging. Dyspnea also decreased with a gain of 11% forced expiratory volume 1/forced vital capacity. A high-sensitivity athletic training cognitive test showed an overall 27% increase in aggregate score. A significant portion of this was attributed to changes in visual clarity and decision-making speed. Post-treatment EEG showed a shift from predominantly delta waves to more synchronized alpha wave patterns during the resting state. Brain stimulation techniques appear to be showing early signs of success with long-COVID symptoms. This is the first case describing the use of a magnetic stimulation technique with quantitative test results and recorded EEG changes. Given the early success in this patient with cognition, dyspnea, and anosmia, this noninvasive treatment modality warrants further research.}, } @article {pmid37267081, year = {2023}, author = {Nguyen, NN and Dudouet, P and Dhiver, C and Gautret, P}, title = {Pericarditis related to post-acute COVID infection: A case report and review of the literature.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {70}, number = {2}, pages = {100-110}, doi = {10.1556/030.2023.02055}, pmid = {37267081}, issn = {1588-2640}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; *Pericarditis/diagnosis/drug therapy/etiology ; Aspirin/therapeutic use ; Colchicine/therapeutic use ; Chest Pain/complications/drug therapy ; }, abstract = {Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy.Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.}, } @article {pmid37266140, year = {2023}, author = {Wieteska-Miłek, M and Kuśmierczyk-Droszcz, B and Betkier-Lipińska, K and Szmit, S and Florczyk, M and Zieliński, P and Hoffman, P and Krzesińki, P and Kurzyna, M}, title = {Long COVID syndrome after SARS-CoV-2 survival in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.}, journal = {Pulmonary circulation}, volume = {13}, number = {2}, pages = {e12244}, pmid = {37266140}, issn = {2045-8932}, abstract = {Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients have a more severe COVID-19 course than the general population. Many patients report different persistent symptoms after SARS-CoV-2 infection. The aim of our study is to analyze the prevalence of long COVID-19 symptoms and assess if COVID-19 affects pulmonary hypertension (PH) prognosis. PAH/CTEPH patients who survived COVID-19 for at least 3 months before visiting the PH centers were included in the study. The patients were assessed for symptoms in acute phase of SARS-CoV-2 infection and persisting in follow-up visit, WHO functional class, 6-min walk distance, NT-proBNP concentration. The COMPERA 2.0 model was used to calculate 1-year risk of death due to PH at baseline and at follow-up. Sixty-nine patients-54 (77.3%) with PAH and 15 (21.7%) with CTEPH, 68% women, with a median age of 47.5 years (IQR 37-68)-were enrolled in the study. About 17.1% of patients were hospitalized due to COVID-19 but none in an ICU. At follow-up (median: 155 days after onset of SARS-CoV-2 symptoms), 62% of patients reported at least 1 COVID-19-related symptom and 20% at least 5 symptoms. The most frequently reported symptoms were: fatigue (30%), joint pain (23%), muscle pain (17%), nasal congestion (17%), anosmia (13%), insomnia (13%), and dyspnea (12%). Seventy-two percent of PH patients had a low or intermediate-low risk of 1-year death due to PH at baseline, and 68% after COVID-19 at follow-up. Over 60% of PAH/CTEPH patients who survived COVID-19 suffered from long COVID-19 syndrome, but the calculated 1-year risk of death due to PH did not change significantly after surviving mild or moderate COVID-19.}, } @article {pmid37265584, year = {2023}, author = {Perumal, R and Shunmugam, L and Naidoo, K and Wilkins, D and Garzino-Demo, A and Brechot, C and Vahlne, A and Nikolich, J}, title = {Biological mechanisms underpinning the development of long COVID.}, journal = {iScience}, volume = {26}, number = {6}, pages = {106935}, pmid = {37265584}, issn = {2589-0042}, support = {MC_PC_16022/MRC_/Medical Research Council/United Kingdom ; }, abstract = {As COVID-19 evolves from a pandemic to an endemic disease, the already staggering number of people that have been or will be infected with SARS-CoV-2 is only destined to increase, and the majority of humanity will be infected. It is well understood that COVID-19, like many other viral infections, leaves a significant fraction of the infected with prolonged consequences. Continued high number of SARS-CoV-2 infections, viral evolution with escape from post-infection and vaccinal immunity, and reinfections heighten the potential impact of Long COVID. Hence, the impact of COVID-19 on human health will be seen for years to come until more effective vaccines and pharmaceutical treatments become available. To that effect, it is imperative that the mechanisms underlying the clinical manifestations of Long COVID be elucidated. In this article, we provide an in-depth analysis of the evidence on several potential mechanisms of Long COVID and discuss their relevance to its pathogenesis.}, } @article {pmid37264854, year = {2023}, author = {Mahmoodi, Z and Bahrami, G and Shahrestanaki, E and Seddighi, H and Ghavidel, N}, title = {Clinical and Socio-Demographic Variables Associated With Long COVID-19: A Cross-Sectional Study.}, journal = {Clinical nursing research}, volume = {32}, number = {6}, pages = {947-953}, pmid = {37264854}, issn = {1552-3799}, mesh = {Cross-Sectional Studies ; SARS-CoV-2 ; Reinfection ; Female ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Demography ; }, abstract = {Considering the importance of long COVID-19 (LC), this study aimed to investigate the relationship between clinical/sociodemographic factors and LC symptoms (LCS). This online cross-sectional study was conducted on 308 people infected with COVID-19 in Alborz, Iran, from April 1 to June 1, 2022. Multivariable logistic regression models were applied to measure the association between the LCS with other variables. Overall, 76.6% of participants had at least one LCS. Results from the multivariate logistic regression analysis showed that females (crude odds ratio [OR] [95% confidence interval (CI)]: 2.725 [1.42, 5.22]), educated persons (3.747 [1.58, 8.84]), people with a higher number of COVID-19 reinfection (2.280 [1.30, 3.97]), having an underlying disease (1.996 [1.01, 3.93]), and COVID-19 severity (3.321 [1.037, 10.635]) had higher odds of LC than others (all p < .05). Study findings provide additional clinical/sociodemographic data on risk for LC. These data may inform future research and clinical practice for potential risk identification and early intervention.}, } @article {pmid37264687, year = {2023}, author = {Rahmati, M and Yon, DK and Lee, SW and Udeh, R and McEVoy, M and Kim, MS and Gyasi, RM and Oh, H and López Sánchez, GF and Jacob, L and Li, Y and Koyanagi, A and Shin, JI and Smith, L}, title = {New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies.}, journal = {Journal of medical virology}, volume = {95}, number = {6}, pages = {e28833}, doi = {10.1002/jmv.28833}, pmid = {37264687}, issn = {1096-9071}, mesh = {Child ; Humans ; Adolescent ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 1/complications/epidemiology ; SARS-CoV-2 ; *Diabetic Ketoacidosis ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.}, } @article {pmid37263366, year = {2023}, author = {Ley, H and Skorniewska, Z and Harrison, PJ and Taquet, M}, title = {Risks of neurological and psychiatric sequelae 2 years after hospitalisation or intensive care admission with COVID-19 compared to admissions for other causes.}, journal = {Brain, behavior, and immunity}, volume = {112}, number = {}, pages = {85-95}, pmid = {37263366}, issn = {1090-2139}, support = {NIHR203316/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Retrospective Studies ; *Brain Ischemia ; *Stroke ; Critical Care ; Hospitalization ; *Encephalitis ; Intracranial Hemorrhages ; }, abstract = {The association between COVID-19 and subsequent neurological and psychiatric disorders is well established. However, two important questions remain unanswered. First, what are the risks in those admitted to intensive care unit (ICU) with COVID-19? Admission to ICU is itself associated with neurological and psychiatric sequelae and it is not clear whether COVID-19 further increases those risks or changes their profile. Second, what are the trajectories of neurological and psychiatric risks in patients admitted to hospital or ICU with COVID-19, and when do the risks subside? We sought to answer these two questions using a retrospective cohort study based on electronic health records (EHR) data from the TriNetX Analytics Network (covering 89 million patients, mostly in the USA). Cohorts of patients admitted to hospital or ICU with COVID-19 were propensity score-matched (for 82 covariates capturing risk factors for COVID-19 and more severe COVID-19 illness) to patients admitted to hospital or ICU (respectively) for any other reason. Matched cohorts were followed for up to two years and the risk of 14 neurological and psychiatric outcomes were compared. A total of 280,173 patients admitted to hospital and 46,573 patients admitted to ICU with COVID-19 were successfully matched to an equal number of patients admitted to hospital or ICU for any other reason. Those hospitalised with COVID-19 were found to be at a greater risk of a range of neurological and psychiatric outcomes including seizure/epilepsy, encephalitis, myoneural junction/muscle disease, Guillain-Barré syndrome (GBS), dementia, cognitive deficits, psychotic disorder, mood and anxiety disorders, but not ischaemic stroke or intracranial haemorrhage. When risks were elevated after COVID-19, most remained so for the whole two years of follow-up (except for mood and anxiety disorders). Risk profiles and trajectories were substantially different among those admitted to ICU: compared to those admitted for any other reasons, those admitted with COVID-19 were at a greater risk of myoneural junction/muscle disease, GBS, cognitive deficits and anxiety disorder, but at a significantly lower risk of ischaemic stroke, intracranial haemorrhage, encephalitis, and mood disorder. When elevated, the risks in those admitted to ICU with COVID-19 were mostly short-lived. In summary, risks of neurological and psychiatric sequelae in patients hospitalised with COVID-19 are wide ranging and long standing whereas those in patients admitted to ICU with COVID-19 are similar to, or lower than, the risks observed post-ICU admission for any other cause. These contrasting risk trajectories are relevant for researchers, clinicians, patients, and policymakers.}, } @article {pmid37261628, year = {2023}, author = {Kleebayoon, A and Wiwanitkit, V}, title = {Nutritional deficiencies and long COVID: correspondence.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {3333}, pmid = {37261628}, issn = {1568-5608}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Malnutrition ; }, } @article {pmid37261215, year = {2023}, author = {Chilunga, FP and Appelman, B and van Vugt, M and Kalverda, K and Smeele, P and van Es, J and Wiersinga, WJ and Rostila, M and Prins, M and Stronks, K and Norredam, M and Agyemang, C}, title = {Differences in incidence, nature of symptoms, and duration of long COVID among hospitalised migrant and non-migrant patients in the Netherlands: a retrospective cohort study.}, journal = {The Lancet regional health. Europe}, volume = {29}, number = {}, pages = {100630}, pmid = {37261215}, issn = {2666-7762}, abstract = {BACKGROUND: Comprehensive data on long COVID across ethnic and migrant groups are lacking. We investigated incidence, nature of symptoms, clinical predictors, and duration of long COVID among COVID-19 hospitalised patients in the Netherlands by migration background (Dutch, Turkish, Moroccan, and Surinamese origin, Others).

METHODS: We used COVID-19 admissions and follow up data (January 2021-July 2022) from Amsterdam University Medical Centers. We calculated long COVID incidence proportions per NICE guidelines by migration background and assessed for clinical predictors via robust Poisson regressions. We then examined associations between migration background and long COVID using robust Poisson regressions and adjusted for derived clinical predictors, and other biologically relevant factors. We also assessed long COVID symptom persistence at one-year post-discharge.

FINDINGS: 1886 patients were included. 483 patients had long COVID (26%, 95% CI 24-28%) at 12 weeks post-discharge. Symptoms like dizziness, joint pain, insomnia, and headache varied by migration background. Clinical predictors of long COVID were female sex, hospital admission duration, intensive care unit admission, and receiving oxygen, or corticosteroid therapy. Long COVID risk was higher among patients with migration background than Dutch origin patients after adjustments for derived clinical predictors, age, smoking, vaccination status, comorbidities and remdesivir treatment. Only 14% of long COVID symptoms persisted at one-year post-discharge.

INTERPRETATION: There are significant differences in occurrence, nature of symptoms, and duration of long COVID by migration background. Studies assessing the spectrum of functional limitation and access to post-COVID healthcare are needed to help plan for appropriate and accessible healthcare interventions.

FUNDING: The Amsterdam UMC COVID-19 biobank is supported by the Amsterdam UMC Corona Research Fund and the Talud Foundation (Stichting Talud). The current analyses were supported by the Novo Nordisk Foundation [NNF21OC0067528].}, } @article {pmid37261214, year = {2023}, author = {Zheng, B and Vivaldi, G and Daines, L and Leavy, OC and Richardson, M and Elneima, O and McAuley, HJC and Shikotra, A and Singapuri, A and Sereno, M and Saunders, RM and Harris, VC and Houchen-Wolloff, L and Greening, NJ and Pfeffer, PE and Hurst, JR and Brown, JS and Shankar-Hari, M and Echevarria, C and De Soyza, A and Harrison, EM and Docherty, AB and Lone, N and Quint, JK and Chalmers, JD and Ho, LP and Horsley, A and Marks, M and Poinasamy, K and Raman, B and Heaney, LG and Wain, LV and Evans, RA and Brightling, CE and Martineau, A and Sheikh, A and , }, title = {Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls.}, journal = {The Lancet regional health. Europe}, volume = {29}, number = {}, pages = {100635}, pmid = {37261214}, issn = {2666-7762}, support = {209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; SP/17/16/33519/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea.

METHODS: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up.

FINDINGS: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01-1.03), male (1.54, 1.16-2.04), neither obese nor severely obese (1.82, 1.06-3.13 and 4.19, 2.14-8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09-2.22) or cardiovascular disease (1.33, 1.00-1.79), and shorter hospital admission (1.01 per day, 1.00-1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission).

INTERPRETATION: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19.

FUNDING: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care.COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders.}, } @article {pmid37259825, year = {2023}, author = {Soomägi, A and Meister, T and Vorobjov, S and Suija, K and Kalda, R and Uusküla, A}, title = {Fear of COVID-19 among patients with prior SARS-CoV-2 infection: A cross-sectional study in Estonian family practices.}, journal = {The European journal of general practice}, volume = {29}, number = {2}, pages = {2195163}, pmid = {37259825}, issn = {1751-1402}, mesh = {Adult ; Male ; Estonia/epidemiology ; Cross-Sectional Studies ; SARS-CoV-2 ; Fear ; Female ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Phobic Disorders ; Middle Aged ; Humans ; Family Practice ; }, abstract = {BACKGROUND: Fear of coronavirus disease (COVID-19) has been associated with significant health effects.

OBJECTIVES: To assess COVID-19 fear and investigate factors associated with higher fear among COVID-19 survivors over 6 months after infection.

METHODS: Cross-sectional study using multistage sampling (family practices within the highest 5th percentile of numbers of SARS-CoV-2 infected patients and random sample of patients within these practices) performed from March 15 to 17 July 2021. Adult patients with a laboratory-confirmed history of COVID-19 were recruited for a self-administered 79-item questionnaire including demographics, self-rated health, physical activity, COVID-19 characteristics, severity and the fear of COVID-19 Scale (FCV-19S). Comorbidity data were extracted from Estonian Health Insurance Fund. Logistic regression models were used to evaluate factors associated with COVID-19 fear.

RESULTS: Of 341 participants included, 60% were women, 24.2% were hospitalised due to COVID-19 and 22.2% had long COVID, 143 (42%) participants reported high levels of fear (cut-off FCV-19S >17.8). Higher fear was associated with being female (aOR 2.12, 95% CI 1.14-3.95), age ≥61 years (aOR 3.23, 95% CI 1.28-8.16), two-member-households (aOR 3.70, 95% CI 1.40-9.77) physical inactivity 6 months prior to COVID-19 (aOR 3.53, 95% CI 1.26-9.95), and symptom severity during acute COVID-19. Long COVID was not associated with higher COVID-19 fear (aOR 1.82 95% CI 0.91-3.63).

CONCLUSION: Almost half of participants reported COVID-19 fear more than 6 months after infection. Greater fear was associated with sociodemographic factors, physical activity prior to COVID-19 and COVID-19 symptom severity. There is a need to target this population to develop appropriate interventions.}, } @article {pmid37258824, year = {2023}, author = {C Trudzinski, F}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {165}, number = {11}, pages = {26}, doi = {10.1007/s15006-023-2744-z}, pmid = {37258824}, issn = {1613-3560}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37255981, year = {2023}, author = {Kinoshita, H and Kurashige, T and Fukuda, T and Morita, M and Maeda, S and Kanegawa, M and Sumimoto, Y and Masada, K and Shimonaga, T and Sugino, H}, title = {The impact that myocarditis for post-acute COVID-19 syndrome may be dermatomyositis-like myocarditis: A case report.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e16512}, pmid = {37255981}, issn = {2405-8440}, abstract = {Myocarditis is often reported as a complication of COVID-19 infection or post-vaccination, but there are few reports of "myocarditis for Post-acute COVID-19 syndrome", and many unknowns still remain. Apart from that, an association between COVID-19 infection and dermatomyositis has also been reported. We describe the clinical presentation of acute myocarditis in a patient who had developed COVID-19 syndrome one-month earlier. A healthy 49-year-old man experienced typical COVID-19 symptoms. Thirty-two days later, he was admitted because of fever and severe fatigue, chest pain and bradycardia. Blood tests showed major inflammation. PCR for SARS-CoV-2 on nasopharyngeal swab (ID NOW™) was positive, but diagnosed as a previous infection due to a high CT value. Because of haemodynamic worsening with both an increase in cardiac troponin I and NT-pro BNP levels and reduced wall motion on echocardiography, acute myocarditis was suspected. Myocardial biopsy revealed severe lymphocytic infiltration and interstitial edema between myocardial fibers. These findings led to the diagnosis of fulminant myocarditis. Interestingly, myocardium was also stained with human myxovirus resistance protein 1 (MxA). We consider that there may be an aspect of "dermatomyositis-like myocarditis with SARS-CoV-2" in our case. This is the first case of fulminant myocarditis for Post-acute COVID-19 syndrome in which diagnosis of active myocarditis was proven by pathological examination following myocardial biopsy and strong association with dermatomyositis was suggested pathologically.}, } @article {pmid37255928, year = {2023}, author = {El-Rhermoul, FZ and Fedorowski, A and Eardley, P and Taraborrelli, P and Panagopoulos, D and Sutton, R and Lim, PB and Dani, M}, title = {Autoimmunity in Long Covid and POTS.}, journal = {Oxford open immunology}, volume = {4}, number = {1}, pages = {iqad002}, pmid = {37255928}, issn = {2633-6960}, abstract = {Orthostatic intolerance and other autonomic dysfunction syndromes are emerging as distinct symptom clusters in Long Covid. Often accompanying these are common, multi-system constitutional features such as fatigue, malaise and skin rashes which can signify generalized immune dysregulation. At the same time, multiple autoantibodies are identified in both Covid-related autonomic disorders and non-Covid autonomic disorders, implying a possible underlying autoimmune pathology. The lack of specificity of these findings precludes direct interpretations of cause and association, but their prevalence with its supporting evidence is compelling.}, } @article {pmid37255755, year = {2023}, author = {Román-Montes, CM and Flores-Soto, Y and Guaracha-Basañez, GA and Tamez-Torres, KM and Sifuentes-Osornio, J and González-Lara, MF and de León, AP}, title = {Post-COVID-19 syndrome and quality of life impairment in severe COVID-19 Mexican patients.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1155951}, pmid = {37255755}, issn = {2296-2565}, mesh = {Male ; Humans ; Female ; Adult ; Middle Aged ; *COVID-19/epidemiology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cross-Sectional Studies ; }, abstract = {INTRODUCTION: Post-COVID-19 syndrome (PCS) usually occurs 3 months after the onset of COVID-19 with a symptom duration of at least 2 months without an alternative diagnosis.

OBJECTIVE: This study aimed to describe the prevalence, characteristics, and impact on the quality of life (QoL) of post-COVID-19 syndrome in patients with a history of hospitalization for COVID-19.

MATERIALS AND METHODS: We conducted a cross-sectional study. Patients who required hospitalization due to COVID-19 between March 2020 and October 2021 were invited to answer a PCS questionnaire and the EQ-5D instrument. A total of 246 patients were included: 187 (76%) met the definition of PCS and 54% were men, with a median age of 50 years (IQR 41-63).

RESULTS: From 187 patients with PCS, the median time to symptom onset after hospital discharge was 1 day (IQR 1-20), and the median symptom duration was 150 days (IQR 90-225). A total of 27 different symptoms were reported; the most frequent were difficulty concentrating (81%), dyspnea (75%), arthralgia (71%), fatigue (68%), and hair loss (60%). Some symptoms, such as difficulty concentrating, arthralgia/myalgia, and hair loss, were more prevalent in women with PCS. Patients with PCS had a higher frequency of tobacco smoking (37 vs. 4%, p = 0.02) and increased severity of lung involvement in the initial chest tomography (75 vs. 58%, p = 0.01) than those without PCS. Patients with PCS were less likely to receive antivirals (15.5 vs. 27%, p = 0.04). No difference between ICU admission, mechanical ventilation, and length of hospital stay was found. Patients with PCS had a lower visual analog scale result for EQ-5D vs. those without (80 [IQR 70-90] vs. 89.5 [IQR 75-90], p = 0.05). All five QoL dimensions were affected in PCS patients, showing increased pain/discomfort (67 vs. 39%, p = < 0.001), difficulties in performing usual activities (39.2 vs. 20.3%, p = 0.03), and anxiety/depression (57.5 vs. 37%, p = 0.02).

CONCLUSION: PCS occurred in 76% of hospitalized patients with prolonged duration and QoL impairment. Neurological symptoms such as difficulty concentrating were the most frequent symptoms. Timely diagnostic and therapeutic interventions are required.}, } @article {pmid37255668, year = {2023}, author = {Schröder, J and Bäuerle, A and Jahre, LM and Skoda, EM and Stettner, M and Kleinschnitz, C and Teufel, M and Dinse, H}, title = {Acceptance, drivers, and barriers to use eHealth interventions in patients with post-COVID-19 syndrome for management of post-COVID-19 symptoms: a cross-sectional study.}, journal = {Therapeutic advances in neurological disorders}, volume = {16}, number = {}, pages = {17562864231175730}, pmid = {37255668}, issn = {1756-2856}, abstract = {BACKGROUND: Post-COVID-19 syndrome is a new and debilitating disease without adequate treatment options. eHealth could be a reasonable approach for symptom management.

OBJECTIVES: This study aims to evaluate the acceptance for eHealth interventions for symptom management in individuals with post-COVID-19 syndrome, as well as drivers and barriers influencing acceptance.

DESIGN: Cross-sectional study.

METHODS: This study was conducted from January 19 until 24 May 2022. Recruitment took place with a web-based survey. Acceptance and predictors of eHealth interventions were measured by the extended UTAUT model. Included in the model were the core predictor performance expectancy, social influence, and effort expectancy. Previously diagnosed mental illness was estimated and mental health by using the well-established Generalized Anxiety Disorder Scale-7 and the Patient Health Questionnaire Depression Scale. The effect of sociodemographic and medical data was assessed. Multiple hierarchical regression analyses as well as group comparisons were performed.

RESULTS: 342 individuals with post-COVID-19 syndrome were examined. The acceptance of eHealth interventions for symptom management was moderate to high (M = 3.60, SD = 0.89). Acceptance was significantly higher in individuals with lower/other education, patients with moderate to severe symptoms during initial COVID-19 infection, still significantly impaired patients, and individuals with a mental illness. Identified predictors of acceptance were age (β = .24, p < .001), current condition including moderate (β = .49, p = .002) and still significantly impaired (β = .67, p < .001), digital confidence (β = .19, p < .001), effort expectancy (β = .26, p < .001), performance expectancy (β = .33, p < .001), and social influence (β = .26, p < .001).

CONCLUSION: Patients with post-COVID-19 syndrome reported a satisfying level of acceptance and drivers and barriers could be identified. These factors need to be considered for the implementation and future use of eHealth interventions.}, } @article {pmid37255048, year = {2023}, author = {Riera-Canales, C and Llanos-Chea, A}, title = {COVID-19 and the gastrointestinal tract in children.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {5}, pages = {585-589}, pmid = {37255048}, issn = {1531-698X}, mesh = {Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Inflammatory Bowel Diseases ; *Irritable Bowel Syndrome ; Gastrointestinal Tract ; }, abstract = {PURPOSE OF REVIEW: This is an overview of the effects of COVID-19 in the gastrointestinal tract in children, and current evidence of the impact of COVID-19 in pediatric patients with chronic gastrointestinal conditions, including inflammatory bowel disease (IBD), chronic liver disease, and disorders of the gut-brain interaction.

RECENT FINDINGS: Children with COVID-19 have a milder course and more favorable outcomes than adults, even in those with immunosuppression due to IBD or liver transplantation. Children with chronic gastrointestinal conditions do not have worse clinical outcomes than healthy children and infection itself has not been linked to an increased incidence of conditions such as IBD and celiac disease, but results regarding post-infectious irritable bowel syndrome are mixed.

SUMMARY: Research specific to pediatrics is needed, particularly in post-infectious disorders of the gut-brain interaction (PI-DGBIs) and long COVID-19. Data extrapolated from adult trials may not apply to children, as their clinical course is different. PI-DGBIs and long COVID-19 require special attention, as they represent a major morbidity burden in children.}, } @article {pmid37253159, year = {2023}, author = {Gallegos, M and Morgan, ML and Burgos-Videla, C and Caycho-Rodríguez, T and Martino, P and Cervigni, M}, title = {The impact of long Covid on people's capacity to work.}, journal = {Annals of work exposures and health}, volume = {67}, number = {7}, pages = {801-804}, doi = {10.1093/annweh/wxad029}, pmid = {37253159}, issn = {2398-7316}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Occupational Exposure ; Public Health ; }, abstract = {This commentary addresses the post-COVID-19 syndrome and its implications for workers' health. Post-COVID-19 syndrome consists of a set of physiological and psychological symptoms resulting from SARS-CoV-2 (COVID-19) infection, which occur continuously for several weeks or months. Therefore, it is an affectation that has multiple consequences for the recovery of people's health, and compromises the ability to perform daily activities, including work, whether in person or remotely. Although several studies have been published so far, and several long-term consequences on people's health have been demonstrated, most have not adequately delved into the implications for the health of workers, their families, and the socioeconomic cost for governments. The aim of this paper is to highlight this public health issue and to encourage more specialized research.}, } @article {pmid37252741, year = {2023}, author = {Wang, S and Huang, T and Weisskopf, MG and Kang, JH and Chavarro, JE and Roberts, AL}, title = {Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post-COVID-19 Condition.}, journal = {JAMA network open}, volume = {6}, number = {5}, pages = {e2315885}, pmid = {37252741}, issn = {2574-3805}, support = {U01 HL145386/HL/NHLBI NIH HHS/United States ; R01 HD094725/HD/NICHD NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; R01 HD057368/HD/NICHD NIH HHS/United States ; R24 ES028521/ES/NIEHS NIH HHS/United States ; K01 HL143034/HL/NHLBI NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; *COVID-19/epidemiology ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; Sleep Quality ; }, abstract = {IMPORTANCE: The association of multiple healthy sleep dimensions with post-COVID-19 condition (PCC), also known as long COVID, has not been investigated.

OBJECTIVE: To examine whether multidimensional sleep health before and during the COVID-19 pandemic, prior to SARS-CoV-2 infection, was associated with the risk of PCC.

This prospective cohort study (2015-2021) included Nurses' Health Study II participants who reported testing positive (n = 2303) for SARS-CoV-2 infection in a substudy series of COVID-19-related surveys (n = 32 249) between April 2020 and November 2021. After exclusion for incomplete information about sleep health and nonresponse to a question about PCC, 1979 women were included in the analysis.

EXPOSURES: Sleep health was measured both before (June 1, 2015, to May 31, 2017) and early (April 1 to August 31, 2020) in the COVID-19 pandemic. Prepandemic sleep score was defined according to 5 dimensions: morning chronotype (assessed in 2015), 7 to 8 hours of sleep per day, low insomnia symptoms, no snoring, and no frequent daytime dysfunction (all assessed in 2017). On the first COVID-19 substudy survey (returned between April and August 2020), average daily sleep duration and sleep quality for the past 7 days were queried.

MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection and PCC (≥4 weeks of symptoms) were self-reported during 1 year of follow-up. Comparisons were examined between June 8, 2022, and January 9, 2023, using Poisson regression models.

RESULTS: Of the 1979 participants reporting SARS-CoV-2 infection (mean [SD] age, 64.7 [4.6] years; 1979 [100%] female; and 1924 [97.2%] White vs 55 [2.8%] other races and ethnicities), 845 (42.7%) were frontline health care workers, and 870 (44.0%) developed PCC. Compared with women who had a prepandemic sleep score of 0 or 1 (least healthy), those who scored 5 (most healthy) had a 30% lower risk of developing PCC (multivariable-adjusted relative risk, 0.70; 95% CI, 0.52-0.94; P for trend <.001). Associations did not differ by health care worker status. No or little daytime dysfunction prepandemic and good sleep quality during the pandemic were independently associated with a lower risk of PCC (relative risk, 0.83 [95% CI, 0.71-0.98] and 0.82 [95% CI, 0.69-0.99], respectively). Results were similar when PCC was defined as having 8 or more weeks of symptoms or as having ongoing symptoms at the time of PCC assessment.

CONCLUSIONS AND RELEVANCE: The findings indicate that healthy sleep measured prior to SARS-CoV-2 infection, both before and during the COVID-19 pandemic, may be protective against PCC. Future research should investigate whether interventions on sleep health may prevent PCC or improve PCC symptoms.}, } @article {pmid37251522, year = {2023}, author = {}, title = {Corrigendum to "Post-COVID-19-associated multiorgan complications or 'long COVID' with literature review and management strategy discussion: A meta-analysis".}, journal = {Health science reports}, volume = {6}, number = {5}, pages = {e1296}, doi = {10.1002/hsr2.1296}, pmid = {37251522}, issn = {2398-8835}, } @article {pmid37251229, year = {2023}, author = {Nordvig, AS and Rajan, M and Lau, JD and Kingery, JR and Mahmud, M and Chiang, GC and De Leon, MJ and Goyal, P}, title = {Brain fog in long COVID limits function and health status, independently of hospital severity and preexisting conditions.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1150096}, pmid = {37251229}, issn = {1664-2295}, support = {P30 AG066462/AG/NIA NIH HHS/United States ; }, abstract = {IMPORTANCE: The U.S. government has named post-acute sequelae of COVID-19 (longCOVID) as influential on disability rates. We previously showed that COVID-19 carries a medical/functional burden at 1 year, and that age and other risk factors of severe COVID-19 were not associated with increased longCOVID risk. Long-term longCOVID brain fog (BF) prevalence, risk factors and associated medical/functional factors are poorly understood, especially after mild SARS-CoV-2 infection.

METHODS: A retrospective observational cohort study was conducted at an urban tertiary-care hospital. Of 1,032 acute COVID-19 survivors from March 3-May 15, 2020, 633 were called, 530 responded (59.2 ± 16.3  years, 44.5% female, 51.5% non-White) about BF prevalence, other longCOVID, post-acute ED/hospital utilization, perceived health/social network, effort tolerance, disability.

RESULTS: At approximately 1-year, 31.9% (n = 169) experienced BF. Acute COVID-19 severity, age, and premorbid cardiopulmonary comorbidities did not differ between those with/without BF at 1  year. Patients with respiratory longCOVID had 54% higher risk of BF than those without respiratory longCOVID. BF associated with sleep disturbance (63% with BF vs.29% without BF, p < 0.0001), shortness of breath (46% vs.18%, p < 0.0001), weakness (49% vs.22%, p < 0.0001), dysosmia/dysgeusia (12% vs.5%, p < 0.004), activity limitations (p < 0.001), disability/leave (11% vs.3%, p < 0.0001), worsened perceived health since acute COVID-19 (66% vs.30%, p < 0.001) and social isolation (40% vs.29%, p < 0.02), despite no differences in premorbid comorbidities and age.

CONCLUSIONS AND RELEVANCE: A year after COVID-19 infection, BF persists in a third of patients. COVID-19 severity is not a predictive risk factor. BF associates with other longCOVID and independently associates with persistent debility.}, } @article {pmid37250390, year = {2023}, author = {Paranhos, ACM and Dias, ARN and Bastos, TDR and Rodrigues, AN and Santana, KHY and Dias, LHA and Dos Santos, LPM and Cerasi, AJ and Mendes, MCN and de Oliveira, CL and Domingues, MM and Koury, GVH and Vasconcelos, PFDC and Souza, GS and Quaresma, JAS and Falcão, LFM}, title = {Persistent olfactory dysfunction associated with poor sleep quality and anxiety in patients with long COVID.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1161904}, pmid = {37250390}, issn = {1662-4548}, abstract = {INTRODUCTION: Poor sleep quality have been widely reported in patients with long COVID. Determining the characteristics, type, severity, and relationship of long COVID with other neurological symptoms is essential for the prognosis and management of poor sleep quality.

METHODS: This cross-sectional study was conducted at a public university in the eastern Amazon region of Brazil between November 2020 and October 2022. The study involved 288 patients with long COVID with self-report neurological symptoms. One hundred thirty-one patients were evaluated by using standardised protocols: Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory, Chemosensory Clinical Research Center (CCRC), and Montreal Cognitive Assessment (MoCA). This study aimed to describe the sociodemographic and clinical characteristics of patients with long COVID with poor sleep quality and their relationship with other neurological symptoms (anxiety, cognitive impairment, and olfactory disorder).

RESULTS: Patients with poor sleep quality were mainly women (76.3%), 44.04 ± 12.73 years old, with >12 years of education (93.1%), and had monthly incomes of up to US $240.00 (54.2%). Anxiety and olfactory disorder were more common in patients with poor sleep quality.

DISCUSSION: Multivariate analysis shows that the prevalence of poor sleep quality was higher in patients with anxiety, and olfactory disorder is associated with poor sleep quality. In this cohort of patients with long COVID, the prevalence of poor sleep quality was highest in the group tested by PSQI and were associated with other neurological symptoms, such as anxiety and olfactory dysfunction. A previous study indicates a significant association between poor sleep quality and psychological disorders over time. Recent studies involving neuroimaging found functional and structural changes in Long COVID patients with persistent olfactory disfunction. Poor sleep quality are integral part of complex changes related to Long COVID and should be part of patient's clinical management.}, } @article {pmid37249286, year = {2023}, author = {Malekpour, M and Khanmohammadi, S and Meybodi, MJE and Shekouh, D and Rahmanian, MR and Kardeh, S and Azarpira, N}, title = {COVID-19 as a trigger of Guillain-Barré syndrome: A review of the molecular mechanism.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {5}, pages = {e875}, pmid = {37249286}, issn = {2050-4527}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Guillain-Barre Syndrome/etiology/complications ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic with serious complications. After coronavirus disease 2019 (COVID-19), several post-acute COVID-19 syndromes (PACSs) and long-COVID sequels were reported. PACSs involve many organs, including the nervous, gustatory, and immune systems. One of the PACSs after SARS-CoV-2 infection and vaccination is Guillain-Barré syndrome (GBS). The incidence rate of GBS after SARS-CoV-2 infection or vaccination is low. However, the high prevalence of COVID-19 and severe complications of GBS, for example, autonomic dysfunction and respiratory failure, highlight the importance of post-COVID-19 GBS. It is while patients with simultaneous COVID-19 and GBS seem to have higher admission rates to the intensive care unit, and demyelination is more aggressive in post-COVID-19 GBS patients. SARS-CoV-2 can trigger GBS via several pathways like direct neurotropism and neurovirulence, microvascular dysfunction and oxidative stress, immune system disruption, molecular mimicry, and autoantibody production. Although there are few molecular studies on the molecular and cellular mechanisms of GBS occurrence after SARS-CoV-2 infection and vaccination, we aimed to discuss the possible pathomechanism of post-COVID-19 GBS by gathering the most recent molecular evidence.}, } @article {pmid37249281, year = {2023}, author = {Kamanzi, P and Mulundu, G and Mutale, K and Mumba, C and Ngalamika, O}, title = {HIV and inflammatory markers are associated with persistent COVID-19 symptoms.}, journal = {Immunity, inflammation and disease}, volume = {11}, number = {5}, pages = {e859}, pmid = {37249281}, issn = {2050-4527}, support = {K43 TW011095/TW/FIC NIH HHS/United States ; U54 CA221204/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *HIV Infections/epidemiology ; Case-Control Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: A proportion of COVID19 survivors may present with long-COVID, which is persistent symptoms lasting four or more weeks post SARS-CoV-2 infection. These symptoms may be mild to severe, and may affect different organ-systems of the body.

AIMS: The main objective of this study was to determine the demographic, clinical and immunological factors associated with long COVID.

MATERIALS & METHODS: We conducted a nested case control study, with a total of 94 study participants initially included, and 64 participants matched for age and sex for biomarker analyses.

RESULTS: 32/94 (34.1%) of all the participants had long COVID. Respiratory symptoms were the most common (59.5%) followed by the musculoskeletal symptoms (28.1%). HIV was an independent predictor of long COVID (adjusted odds ratio = 2.7; p = .037). In all the 64 matched cases and controls, IFN-β was significantly higher among controls than cases. After stratifying by HIV, IL6 was significantly higher among cases than controls in the HIV- group (2.06 vs. 0.81 pg/mL; p = .02). On the other hand, IFN-β was significantly higher among controls than cases in the HIV+ group (251 vs. 0 pg/mL; p = .01).

CONCLUSION: HIV infection is a risk factor for long COVID, and inflammatory markers associated with long COVID may be slightly different for HIV- and HIV+ individuals.}, } @article {pmid37248500, year = {2023}, author = {Putekova, S and Martinkova, J and Urickova, A and Kober, L and Reichertova, S and Plancikova, D and Majdan, M}, title = {The impact of the COVID-19 pandemic on the health and working conditions of nurses and its implications for policies: a cross-sectional study in Slovakia.}, journal = {BMC nursing}, volume = {22}, number = {1}, pages = {185}, pmid = {37248500}, issn = {1472-6955}, abstract = {BACKGROUND: Increased workload and of the health workforce (HW) strained the capacity to maintain essential health services (EHS) during the Coronavirus Disease 2019 (COVID-19) pandemic, while putting them at increased risk of COVID-19 and other consequences to their health. The aim of this study was to assess the impact of COVID-19 on the health, wellbeing, and working conditions of nurses in Slovakia and to identify gaps in policies to be addressed to increase preparedness of the HW for future emergencies.

METHODS: A nation-wide cross-sectional study was conducted among nurses during November-December 2021, referring to the period of January 2021 to November 2021. To assess the differences between impact on HW on various levels of care, respondents were grouped by type of facility: hospital-COVID-19 wards; Hospital-non-covid ward; Outpatient or ER; Other care facilities.

RESULTS: 1170 nurses participated, about 1/3 of them tested positive for COVID-19 by November 2021, mostly developing mild disease. Almost 2/3 reported long-covid symptoms and about 13% reported that they do not plan to get vaccinated against COVID-19. The median of the score of the impact of workload on health was 2.8 (56% of the maximum 5), the median score of mental health-wellbeing was 1.9 (63% of a maximum of 3). The studied impacts in all domains were highest in nurses working in COVID-19 hospital wards. Significant disruptions of health care were reported, with relatively high use of telemedicine to mitigate them. Overall, about 70% of the respondents thought of leaving their job, mostly due to working stress or inadequate pay.

CONCLUSIONS: Our study showed that the COVID-19 pandemic poses a substantial burden on the health, wellbeing and working conditions of nurses in Slovakia and that a large proportion of nurses considered leaving their jobs because of work overload or low salaries. Human resource strategies should be adopted to attract, retain and continuously invest in HW development including in emergency preparedness and response. Such an approach may improve the resilience and preparedness of the health system in Slovakia for future emergencies.}, } @article {pmid37246961, year = {2023}, author = {Arguni, E and Chamida, FM and Indrawanti, R and Rusmawatiningtyas, D and Dewi, YP and Laksanawati, IS}, title = {The Kinetics of Anti-SARS-CoV-2 Antibodies in Pediatric Patients and the Characterization of Post-COVID-19 Condition at 6 Months After Infection: Protocol for a Longitudinal Observational Study.}, journal = {JMIR research protocols}, volume = {12}, number = {}, pages = {e43344}, pmid = {37246961}, issn = {1929-0748}, abstract = {BACKGROUND: Data regarding the kinetics of anti-SARS-CoV-2 antibodies and information about post-COVID-19 condition (colloquially known as "long COVID") in children are scarce, especially in low-income countries. Even though cases of COVID-19 in children are less prevalent than adults, post-COVID-19 condition cases in children are high and have a burden that may impact their growth and development. There are other features of antibody kinetics in connection with SARS-CoV-2 infection that are yet unknown as of this writing, especially in children following infection. Furthermore, the long-term results, risk factors, and underlying pathophysiology are still uncertain. To better understand post-COVID-19 condition in children, it is necessary to further investigate the impact of clinically significant factors such multisystem inflammatory syndrome and disease severity among hospitalized survivors through their SARS-CoV-2 antibody response.

OBJECTIVE: We aim to analyze anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies over time and characterize the signs and symptoms of post-COVID-19 condition in pediatric patients at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection.

METHODS: This is a longitudinal observational study in Indonesia. Pediatric patients diagnosed with COVID-19 by positive molecular assay using nasopharyngeal swab will be tested for anti-SARS-CoV-2 antibodies using the Roche Elecsys Anti-SARS-CoV-2 S assay at the time of diagnosis and at 2 weeks and 1, 3, and 6 months following infection. Antibody titer data will be reported as means and SDs. The respondents' signs and symptoms will be observed up to 6 months after the onset of infection, including the vaccination event, reinfection, rehospitalization, and mortality. The clinical features will be reported as frequencies and percentages.

RESULTS: Participant enrollment began in February 2022. As of September 30, 2022, a total of 58 patients were enrolled. After data collection, results are expected to be analyzed in August 2023.

CONCLUSIONS: This study will allow us to know the kinetics of anti-receptor-binding domain SARS-CoV-2 immunoglobulin G antibodies and data regarding post-COVID-19 condition up to 6 months following infection in the Indonesian pediatric population. Furthermore, this study has the potential to serve as a foundation for government decisions about vaccination programs and prevention measures.

DERR1-10.2196/43344.}, } @article {pmid37245047, year = {2023}, author = {Natarajan, A and Shetty, A and Delanerolle, G and Zeng, Y and Zhang, Y and Raymont, V and Rathod, S and Halabi, S and Elliot, K and Shi, JQ and Phiri, P}, title = {A systematic review and meta-analysis of long COVID symptoms.}, journal = {Systematic reviews}, volume = {12}, number = {1}, pages = {88}, pmid = {37245047}, issn = {2046-4053}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; Mental Health ; }, abstract = {BACKGROUND: Ongoing symptoms or the development of new symptoms following a SARS-CoV-2 diagnosis has caused a complex clinical problem known as "long COVID" (LC). This has introduced further pressure on global healthcare systems as there appears to be a need for ongoing clinical management of these patients. LC personifies heterogeneous symptoms at varying frequencies. The most complex symptoms appear to be driven by the neurology and neuropsychiatry spheres.

METHODS: A systematic protocol was developed, peer reviewed, and published in PROSPERO. The systematic review included publications from the 1st of December 2019-30th June 2021 published in English. Multiple electronic databases were used. The dataset has been analyzed using a random-effects model and a subgroup analysis based on geographical location. Prevalence and 95% confidence intervals (CIs) were established based on the data identified.

RESULTS: Of the 302 studies, 49 met the inclusion criteria, although 36 studies were included in the meta-analysis. The 36 studies had a collective sample size of 11,598 LC patients. 18 of the 36 studies were designed as cohorts and the remainder were cross-sectional. Symptoms of mental health, gastrointestinal, cardiopulmonary, neurological, and pain were reported.

CONCLUSIONS: The quality that differentiates this meta-analysis is that they are cohort and cross-sectional studies with follow-up. It is evident that there is limited knowledge available of LC and current clinical management strategies may be suboptimal as a result. Clinical practice improvements will require more comprehensive clinical research, enabling effective evidence-based approaches to better support patients.}, } @article {pmid37243259, year = {2023}, author = {Baroni, C and Potito, J and Perticone, ME and Orausclio, P and Luna, CM}, title = {How Does Long-COVID Impact Prognosis and the Long-Term Sequelae?.}, journal = {Viruses}, volume = {15}, number = {5}, pages = {}, pmid = {37243259}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/complications ; Diarrhea ; Disease Progression ; Post-Acute COVID-19 Syndrome ; Prognosis ; SARS-CoV-2 ; }, abstract = {CONTEXT: We reviewed what has been studied and published during the last 3 years about the consequences, mainly respiratory, cardiac, digestive, and neurological/psychiatric (organic and functional), in patients with COVID-19 of prolonged course.

OBJECTIVE: To conduct a narrative review synthesizing current clinical evidence of abnormalities of signs, symptoms, and complementary studies in COVID-19 patients who presented a prolonged and complicated course.

METHODS: A review of the literature focused on the involvement of the main organic functions mentioned, based almost exclusively on the systematic search of publications written in English available on PubMed/MEDLINE.

RESULTS: Long-term respiratory, cardiac, digestive, and neurological/psychiatric dysfunction are present in a significant number of patients. Lung involvement is the most common; cardiovascular involvement may happen with or without symptoms or clinical abnormalities; gastrointestinal compromise includes the loss of appetite, nausea, gastroesophageal reflux, diarrhea, etc.; and neurological/psychiatric compromise can produce a wide variety of signs and symptoms, either organic or functional. Vaccination is not associated with the emergence of long-COVID, but it may happen in vaccinated people.

CONCLUSIONS: The severity of illness increases the risk of long-COVID. Pulmonary sequelae, cardiomyopathy, the detection of ribonucleic acid in the gastrointestinal tract, and headaches and cognitive impairment may become refractory in severely ill COVID-19 patients.}, } @article {pmid37243220, year = {2023}, author = {Fernández-de-Las-Peñas, C and Torres-Macho, J and Guijarro, C and Martín-Guerrero, JD and Pellicer-Valero, OJ and Plaza-Manzano, G}, title = {Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study.}, journal = {Viruses}, volume = {15}, number = {5}, pages = {}, pmid = {37243220}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cohort Studies ; SARS-CoV-2 ; Diarrhea/epidemiology ; Survivors ; }, abstract = {This multicenter cohort study used Sankey plots and exponential bar plots to visualize the fluctuating evolution and the trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors during the first 18 months after acute SARS-CoV-2 infection. A total of 1266 previously hospitalized COVID-19 survivors were assessed at four points: hospital admission (T0), at 8.4 months (T1), at 13.2 months (T2), and at 18.3 months (T3) after hospitalization. Participants were asked about their overall gastrointestinal symptoms and particularly diarrhea. Clinical and hospitalization data were collected from hospital medical records. The prevalence of overall gastrointestinal post-COVID symptomatology was 6.3% (n = 80) at T1, 3.99% (n = 50) at T2 and 2.39% (n = 32) at T3. The prevalence of diarrhea decreased from 10.69% (n = 135) at hospital admission (T0), to 2.55% (n = 32) at T1, to 1.04% (n = 14) at T2, and to 0.64% (n = 8) at T3. The Sankey plots revealed that just 20 (1.59%) and 4 (0.32%) patients exhibited overall gastrointestinal post-COVID symptoms or diarrhea, respectively, throughout the whole follow-up period. The recovery fitted exponential curves revealed a decreasing prevalence trend, showing that diarrhea and gastrointestinal symptoms recover during the first two or three years after COVID-19 in previously hospitalized COVID-19 survivors. The regression models did not reveal any symptoms to be associated with the presence of gastrointestinal post-COVID symptomatology or post-COVID diarrhea at hospital admission or at T1. The use of Sankey plots revealed the fluctuating evolution of gastrointestinal post-COVID symptoms during the first two years after infection. In addition, exponential bar plots revealed the decreased prevalence of gastrointestinal post-COVID symptomatology during the first three years after infection.}, } @article {pmid37243092, year = {2023}, author = {Pagel, C and Wilde, H and Tomlinson, C and Mateen, B and Brown, K}, title = {A Methodological Framework for Assessing the Benefit of SARS-CoV-2 Vaccination following Previous Infection: Case Study of Five- to Eleven-Year-Olds.}, journal = {Vaccines}, volume = {11}, number = {5}, pages = {}, pmid = {37243092}, issn = {2076-393X}, support = {MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; SP/19/3/34678/BHF_/British Heart Foundation/United Kingdom ; }, abstract = {Vaccination rates against SARS-CoV-2 in children aged five to eleven years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to eleven, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.}, } @article {pmid37242988, year = {2023}, author = {Jarupan, M and Jantarabenjakul, W and Jaruampornpan, P and Subchartanan, J and Phasomsap, C and Sritammasiri, T and Cartledge, S and Suchartlikitwong, P and Anugulruengkitt, S and Kawichai, S and Puthanakit, T}, title = {Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand.}, journal = {Vaccines}, volume = {11}, number = {5}, pages = {}, pmid = {37242988}, issn = {2076-393X}, support = {RA65/032//Chulalongkorn University/ ; }, abstract = {This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1-91.8) and 79.2% inhibition (61.5-88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8-88.8) and 68.8% inhibition (65.0-91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.}, } @article {pmid37242804, year = {2023}, author = {Akanchise, T and Angelova, A}, title = {Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy.}, journal = {Pharmaceutics}, volume = {15}, number = {5}, pages = {}, pmid = {37242804}, issn = {1999-4923}, abstract = {Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A-C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress.}, } @article {pmid37241210, year = {2023}, author = {Wirth, KJ and Löhn, M}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {5}, pages = {}, pmid = {37241210}, issn = {1648-9144}, mesh = {Female ; Humans ; *Fatigue Syndrome, Chronic/complications/epidemiology ; Dysmenorrhea/complications ; *Endometriosis/complications ; Comorbidity ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood. We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease. We wondered whether some of the identified key pathomechanisms in ME/CFS are also operative in MCA, endometriosis and dysmenorrhea, POTS, decreased cerebral blood flow and SFN, and possibly may provide clues on their causes and frequent co-occurrence. Our analysis indeed provides strong arguments in favor of this assumption, and we conclude that the main pathomechanisms responsible for this association are excessive generation and spillover into the systemic circulation of inflammatory and vasoactive tissue mediators, dysfunctional β2AdR, and the mutual triggering of symptomatology and disease initiation. Overall, vascular dysfunction appears to be a strong common denominator in these linkages.}, } @article {pmid37240704, year = {2023}, author = {Jaramillo, M and Thyvalikakath, TP and Eckert, G and Srinivasan, M}, title = {Characteristics of Chemosensory Perception in Long COVID and COVID Reinfection.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240704}, issn = {2077-0383}, support = {44-762-42//Delta Dental Foundation, USA/ ; }, abstract = {Emerging data suggest an increasing prevalence of persistent symptoms in individuals affected by coronavirus disease-19 (COVID-19). The objective of this study was to determine the relative frequency of altered taste and smell in COVID reinfection (multiple COVID positive tests) and long COVID (one COVID positive test). We sent an electronic survey to patients in the Indiana University Health COVID registry with positive COVID test results, querying if they were experiencing symptoms consistent with long COVID including altered chemosensory perceptions. Among the 225 respondents, a greater long COVID burden and COVID reinfection was observed in women. Joint pain was reported as the most common symptom experienced by 18% of individuals in the long COVID cohort. In the COVID reinfection cohort >20% of individuals reported headache, joint pain, and cough. Taste perception worse than pre-COVID was reported by 29% and 42% of individuals in the long COVID and COVID reinfection cohorts, respectively. Smell perception worse than pre-COVID was reported by 37% and 46% of individuals in long COVID and COVID reinfection cohorts, respectively. Further, Chi-square test suggested significant association between pre-COVID severity of taste/smell perception and headache in both cohorts. Our findings highlight the prevalence of persistent chemosensory dysfunction for two years and longer in long COVID and COVID reinfection.}, } @article {pmid37240639, year = {2023}, author = {Fujita, K and Otsuka, Y and Sunada, N and Honda, H and Tokumasu, K and Nakano, Y and Sakurada, Y and Obika, M and Hagiya, H and Otsuka, F}, title = {Manifestation of Headache Affecting Quality of Life in Long COVID Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240639}, issn = {2077-0383}, support = {JP22K20927 (Y.O.)//Japan Society for the Promotion of Science/ ; 2022 (F.O.).//Ryobi Teien Memory Foundation/ ; }, abstract = {Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.}, } @article {pmid37240616, year = {2023}, author = {Kessler, R and Philipp, J and Wilfer, J and Kostev, K}, title = {Predictive Attributes for Developing Long COVID-A Study Using Machine Learning and Real-World Data from Primary Care Physicians in Germany.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240616}, issn = {2077-0383}, abstract = {(1) In the present study, we used data comprising patient medical histories from a panel of primary care practices in Germany to predict post-COVID-19 conditions in patients after COVID-19 diagnosis and to evaluate the relevant factors associated with these conditions using machine learning methods. (2) Methods: Data retrieved from the IQVIA[TM] Disease Analyzer database were used. Patients with at least one COVID-19 diagnosis between January 2020 and July 2022 were selected for inclusion in the study. Age, sex, and the complete history of diagnoses and prescription data before COVID-19 infection at the respective primary care practice were extracted for each patient. A gradient boosting classifier (LGBM) was deployed. The prepared design matrix was randomly divided into train (80%) and test data (20%). After optimizing the hyperparameters of the LGBM classifier by maximizing the F2 score, model performance was evaluated using several test metrics. We calculated SHAP values to evaluate the importance of the individual features, but more importantly, to evaluate the direction of influence of each feature in our dataset, i.e., whether it is positively or negatively associated with a diagnosis of long COVID. (3) Results: In both the train and test data sets, the model showed a high recall (sensitivity) of 81% and 72% and a high specificity of 80% and 80%; this was offset, however, by a moderate precision of 8% and 7% and an F2-score of 0.28 and 0.25. The most common predictive features identified using SHAP included COVID-19 variant, physician practice, age, distinct number of diagnoses and therapies, sick days ratio, sex, vaccination rate, somatoform disorders, migraine, back pain, asthma, malaise and fatigue, as well as cough preparations. (4) Conclusions: The present exploratory study describes an initial investigation of the prediction of potential features increasing the risk of developing long COVID after COVID-19 infection by using the patient history from electronic medical records before COVID-19 infection in primary care practices in Germany using machine learning. Notably, we identified several predictive features for the development of long COVID in patient demographics and their medical histories.}, } @article {pmid37240555, year = {2023}, author = {Mazzaglia, G}, title = {Long COVID Syndrome: Lesson Learned and Future Implications.}, journal = {Journal of clinical medicine}, volume = {12}, number = {10}, pages = {}, pmid = {37240555}, issn = {2077-0383}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused severe illness and mortality on a global scale, with an impact not witnessed since the 1918-19 Spanish influenza pandemic [...].}, } @article {pmid37239754, year = {2023}, author = {Navas-Otero, A and Calvache-Mateo, A and Martín-Núñez, J and Calles-Plata, I and Ortiz-Rubio, A and Valenza, MC and López, LL}, title = {Characteristics of Frailty in Perimenopausal Women with Long COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {10}, pages = {}, pmid = {37239754}, issn = {2227-9032}, support = {FPU:19/02609//Ministerio de Educación Cultura y Deporte/ ; FPU: 21/00451//Ministerio de Educación Cultura y Deporte/ ; 06195/21D/MA//College of Physiotherapists of Andalucia/ ; }, abstract = {The aim of this study was to compare the prevalence of risk factors for frailty between perimenopausal women with long COVID-19 syndrome, women having successfully recovered from COVID-19, and controls from the community. Women with a diagnosis of long COVID-19 and at least one symptom related to the perimenopausal period, women who had successfully recovered from COVID-19, and healthy women of comparable age were included in this study. Symptom severity and functional disability were assessed with the COVID-19 Yorkshire Rehabilitation Scale, and the presence of frailty was evaluated considering the Fried criteria. A total of 195 women were included in the study, distributed over the three groups. The long COVID-19 group showed a higher prevalence of perimenopausal symptoms and impact of COVID-19. Statistically significant differences were found between the long COVID-19 group and the other two groups for the frailty variables. When studying the associations between frailty variables and COVID-19 symptom impact, significant positive correlations were found. Perimenopausal women with long COVID-19 syndrome present more frailty-related factors and experience a higher range of debilitating ongoing symptoms. A significant relationship is shown to exist between long COVID-19 syndrome-related disability and symptoms and frailty variables, resulting in an increased chance of presenting disability.}, } @article {pmid37239592, year = {2023}, author = {Gunnarsson, DV and Miskowiak, KW and Pedersen, JK and Hansen, H and Podlekareva, D and Johnsen, S and Dall, CH}, title = {Physical Function and Association with Cognitive Function in Patients in a Post-COVID-19 Clinic-A Cross-Sectional Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {10}, pages = {}, pmid = {37239592}, issn = {1660-4601}, mesh = {Humans ; Female ; Middle Aged ; Male ; Cross-Sectional Studies ; Hand Strength/physiology ; *COVID-19/epidemiology ; Cognition/physiology ; *Cognitive Dysfunction/psychology ; }, abstract = {Patients with long-term health sequelae of COVID-19 (post-COVID-19 condition) experience both physical and cognitive manifestations. However, there is still uncertainty about the prevalence of physical impairment in these patients and whether there is a link between physical and cognitive function. The aim was to assess the prevalence of physical impairment and investigate the association with cognition in patients assessed in a post-COVID-19 clinic. In this cross-sectional study, patients referred to an outpatient clinic ≥ 3 months after acute infection underwent screening of their physical and cognitive function as part of a comprehensive multidisciplinary assessment. Physical function was assessed with the 6-Minute Walk Test, the 30 s Sit-to-Stand Test and by measuring handgrip strength. Cognitive function was assessed with the Screen for Cognitive Impairment in Psychiatry and the Trail Making Test-Part B. Physical impairment was tested by comparing the patients' performance to normative and expected values. Association with cognition was investigated using correlation analyses and the possible explanatory variables regarding physical function were assessed using regression analyses. In total, we included 292 patients, the mean age was 52 (±15) years, 56% were women and 50% had been hospitalised during an acute COVID-19 infection. The prevalence of physical impairment ranged from 23% in functional exercise capacity to 59% in lower extremity muscle strength and function. There was no greater risk of physical impairment in previously hospitalised compared with the non-hospitalised patients. There was a weak to moderate association between physical and cognitive function. The cognitive test scores had statistically significant prediction value for all three outcomes of physical function. In conclusion, physical impairments were prevalent amongst patients assessed for post-COVID-19 condition regardless of their hospitalisation status and these were associated with more cognitive dysfunction.}, } @article {pmid37239531, year = {2023}, author = {Isaac, RO and Corrado, J and Sivan, M}, title = {Detecting Orthostatic Intolerance in Long COVID in a Clinic Setting.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {10}, pages = {}, pmid = {37239531}, issn = {1660-4601}, mesh = {Humans ; *Orthostatic Intolerance/diagnosis ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; Dizziness/etiology ; *COVID-19/diagnosis ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology ; *Hypotension, Orthostatic/diagnosis/epidemiology ; }, abstract = {INTRODUCTION: A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS.

METHODS: NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman's rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score.

RESULTS: Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor).

CONCLUSIONS: We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency.}, } @article {pmid37239263, year = {2023}, author = {Rabaiotti, P and Ciracì, C and Donelli, D and Oggioni, C and Rizzi, B and Savi, F and Antonelli, M and Rizzato, M and Moderato, L and Brambilla, V and Ziveri, V and Brambilla, L and Bini, M and Nouvenne, A and Lazzeroni, D}, title = {Effects of Multidisciplinary Rehabilitation Enhanced with Neuropsychological Treatment on Post-Acute SARS-CoV-2 Cognitive Impairment (Brain Fog): An Observational Study.}, journal = {Brain sciences}, volume = {13}, number = {5}, pages = {}, pmid = {37239263}, issn = {2076-3425}, abstract = {Concentration and memory impairment (named "brain fog") represents a frequent and disabling neuropsychological sequela in post-acute COVID-19 syndrome (PACS) patients. The aim of this study was to assess whether neurocognitive function could improve after a multidisciplinary rehabilitation program enhanced with individualized neuropsychological treatment. A prospective monocentric registry of PACS patients consecutively admitted to our Rehabilitation Unit was created. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment at admission and discharge. A total of sixty-four (64) PACS patients, fifty-six (56) of them with brain fog, were treated with a day-by-day individualized psychological intervention of cognitive stimulation (45 min) on top of a standard in-hospital rehabilitation program. The mean duration of the acute-phase hospitalization was 55.8 ± 25.8 days and the mean in-hospital rehabilitation duration was 30 ± 10 days. The mean age of the patients was 67.3 ± 10.4 years, 66% of them were male, none had a previous diagnosis of dementia, and 66% of the entire sample had experienced severe COVID-19. At admission, only 12% of the patients had normal cognitive function, while 57% showed mild, 28% moderate, and 3% severe cognitive impairment. After psychological treatment, a significant improvement in the MoCA score was found (20.4 ± 5 vs. 24.7 ± 3.7; p < 0.0001) as a result of significant amelioration in the following domains: attention task (p = 0.014), abstract reasoning (p = 0.003), language repetition (p = 0.002), memory recall (p < 0.0001), orientation (p < 0.0001), and visuospatial abilities (p < 0.0001). Moreover, the improvement remained significant after multivariate analysis adjusted for several confounding factors. Finally, at discharge, 43% of the patients with cognitive impairment normalized their cognitive function, while 4.7% were discharged with residual moderate cognitive impairment. In conclusion, our study provides evidence of the effects of multidisciplinary rehabilitation enhanced with neuropsychological treatment on improvement in the cognitive function of post-acute COVID-19 patients.}, } @article {pmid37239092, year = {2023}, author = {Siebert, HC and Eckert, T and Bhunia, A and Klatte, N and Mohri, M and Siebert, S and Kozarova, A and Hudson, JW and Zhang, R and Zhang, N and Li, L and Gousias, K and Kanakis, D and Yan, M and Jiménez-Barbero, J and Kožár, T and Nifantiev, NE and Vollmer, C and Brandenburger, T and Kindgen-Milles, D and Haak, T and Petridis, AK}, title = {Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.}, journal = {Biomedicines}, volume = {11}, number = {5}, pages = {}, pmid = {37239092}, issn = {2227-9059}, support = {ERDF//Diabetes-Akademie Bad Mergentheim e. V.. This publication also results from the project implementation: Open Scientific Community for Modern Interdisciplinary Research in Medicine (OPENMED), ITMS2014+: 313011V455 supported by the Operational Programme Int/ ; }, abstract = {The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including [31]P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by [1]H and [31]P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by [31]P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.}, } @article {pmid37238755, year = {2023}, author = {Pérez de la Lastra, JM and Curieses Andrés, CM and Andrés Juan, C and Plou, FJ and Pérez-Lebeña, E}, title = {Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {37238755}, issn = {2304-8158}, support = {Project ProID2020010134//Agencia Canaria de Investigación, Innovación y Sociedad de la Información/ ; Grant PID2019-105838RB-C31//Spanish Ministry of Economy and Competitiveness/ ; project PLEC2022-009507//Spanish Ministry of Science and Innovation/ ; }, abstract = {Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of [•]NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19.}, } @article {pmid37238686, year = {2023}, author = {Maiese, K}, title = {Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.}, journal = {Biomolecules}, volume = {13}, number = {5}, pages = {}, pmid = {37238686}, issn = {2218-273X}, support = {/RA/ARRA NIH HHS/United States ; }, mesh = {Humans ; AMP-Activated Protein Kinases/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; TOR Serine-Threonine Kinases/metabolism ; *Diabetes Mellitus ; *Alzheimer Disease/metabolism ; *Neurodegenerative Diseases/metabolism ; *Metabolic Diseases ; Brain/metabolism ; }, abstract = {It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of β-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.}, } @article {pmid37237560, year = {2023}, author = {Neves, PFMD and Quaresma, JAS and Queiroz, MAF and Silva, CC and Maia, EV and Oliveira, JSS and Neves, CMAD and Mendonça, SDS and Falcão, ASC and Melo, GS and Santos, IBF and Sousa, JR and Santos, EJMD and Vasconcelos, PFDC and Vallinoto, ACR and Falcão, LFM}, title = {Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.}, journal = {Biology}, volume = {12}, number = {5}, pages = {}, pmid = {37237560}, issn = {2079-7737}, support = {#006/2020 and #060/2020//Amazon Foundation for Research Support (FAPESPA)/ ; #09/2021//Secretary of Science, Technology, and Higher, Professional and Technological Education (SECTET)/ ; #401235/2020-3//National Council for Scientific and Technological Development/ ; #406360/2022-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brasil (INCT)/ ; }, abstract = {A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.}, } @article {pmid37236416, year = {2025}, author = {Honda, H and Takamatsu, A and Miwa, T and Tabuchi, T and Taniguchi, K and Shibuya, K and Tokuda, Y}, title = {Prolonged Symptoms after COVID-19 in Japan: A Nationwide Survey of the Symptoms and Their Impact on Patients' Quality of Life.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {98-107.e4}, pmid = {37236416}, issn = {1555-7162}, mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology/complications/psychology ; Male ; Female ; Japan/epidemiology ; Middle Aged ; Cross-Sectional Studies ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; SARS-CoV-2 ; Comorbidity ; Headache/epidemiology/etiology ; }, abstract = {BACKGROUND: Clinical details of long COVID are still not well understood because of potential confounding with a wide range of pre-existing comorbidities.

METHODS: The present study used datasets from a nationwide, cross-sectional, online survey. We determined which prolonged symptoms were more likely to be associated with post-COVID condition after adjusting for a wide range of comorbidities and baseline characteristics. This study also used the EuroQol 5 Dimension 5 Level (EQ-5D-5L) and Somatic Symptom Scale-8 to assess health-related quality of life (QOL) and somatic symptoms in individuals with a previous history of COVID-19, defined as the diagnosis of COVID-19 made at least 2 months prior to the online survey.

RESULTS: In total, 19,784 respondents were included for analysis; of these, 2397 (12.1%) had a previous history of COVID-19. The absolute difference of adjusted prevalence of symptoms attributed to prolonged symptoms after COVID-19 ranged from -0.4% to +2.0%. Headache (adjusted odds ratio [aOR]: 1.22; 95% confidence interval [95% CI]:1.07-1.39), chest discomfort (aOR:1.34, 95% CI:1.01-1.77), dysgeusia (aOR: 2.05, 95% CI: 1.39-3.04), and dysosmia (aOR: 1.96, 95% CI: 1.35-2.84) were independently associated with a previous history of COVID-19. Individuals with a previous history of COVID-19 had lower health-related QOL scores.

CONCLUSIONS: After adjusting for potential comorbidities and confounders, clinical symptoms, such as headache, chest discomfort, dysgeusia, and dysosmia, were found to be independently associated with a previous history of COVID-19, which was diagnosed 2 or more months previously. These protracted symptoms might have impacted QOL and the overall somatic symptom burden in subjects with a previous history of COVID-19.}, } @article {pmid37235337, year = {2023}, author = {Manu, P}, title = {Therapeutic Vaccination Is the Most Promising Intervention for Long COVID.}, journal = {American journal of therapeutics}, volume = {30}, number = {4}, pages = {e372-e373}, doi = {10.1097/MJT.0000000000001641}, pmid = {37235337}, issn = {1536-3686}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; }, } @article {pmid37234804, year = {2023}, author = {Liu, C and Liu, N and Zeng, Y and Xiao, B and Wang, P and Zhou, C and Xia, Y and Zhao, Z and Xiao, T and Li, H}, title = {COVID-19 and sarcopenia-related traits: a bidirectional Mendelian randomization study.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1162936}, pmid = {37234804}, issn = {1664-2392}, mesh = {Humans ; Aged ; *Sarcopenia/epidemiology/genetics ; *COVID-19/complications/epidemiology/genetics ; Mendelian Randomization Analysis ; Pandemics ; Muscle, Skeletal ; }, abstract = {BACKGROUND: Emerging evidence suggested that coronavirus disease 2019 (COVID-19) patients were more prone to acute skeletal muscle loss and suffer sequelae, including weakness, arthromyalgia, depression and anxiety. Meanwhile, it was observed that sarcopenia (SP) was associated with susceptibility, hospitalization and severity of COVID-19. However, it is not known whether there is causal relationship between COVID-19 and SP-related traits. Mendelian randomization (MR) was a valid method for inferring causality.

METHODS: Data was extracted from the COVID-19 Host Genetic Initiative and the UK Biobank without sample overlapping. The MR analysis was performed with inverse variance weighted, weighted median, MR-Egger, RAPS and CAUSE, MR-APSS. Sensitivity analysis was conducted with MR-Egger intercept test, Cochran's Q test, MR-PRESSO to eliminate pleiotropy.

RESULTS: There was insufficient result in the MR-APSS method to support a direct causal relationship after the Bonferroni correction. Most other MR results were also nominally consistent with the MR-APSS result.

CONCLUSIONS: Our study first explored the causal relationship between COVID-19 and SP-related traits, but the result indicated that they may indirectly interact with each other. We highlighted that older people had better absorb enough nutrition and strengthen exercise to directly cope with SP during the COVID-19 pandemic.}, } @article {pmid37234173, year = {2023}, author = {Lamacchia, C and Mongin, D and Juillard, C and Antinori-Malaspina, P and Gabay, C and Finckh, A and Pagano, S and Vuilleumier, N}, title = {Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1154058}, pmid = {37234173}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Apolipoprotein A-I ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Cohort Studies ; *Rheumatic Fever ; Immunoglobulin G ; }, abstract = {OBJECTIVES: To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients.

METHODS: This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions.

RESULTS: There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1-25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08-0.26).

CONCLUSIONS: SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.}, } @article {pmid37234076, year = {2023}, author = {Pollack, B and von Saltza, E and McCorkell, L and Santos, L and Hultman, A and Cohen, AK and Soares, L}, title = {Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review.}, journal = {Frontiers in rehabilitation sciences}, volume = {4}, number = {}, pages = {1122673}, pmid = {37234076}, issn = {2673-6861}, abstract = {Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID. These associated illnesses, whose patients are 70%-80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause. We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.}, } @article {pmid37233729, year = {2023}, author = {Mohandas, S and Jagannathan, P and Henrich, TJ and Sherif, ZA and Bime, C and Quinlan, E and Portman, MA and Gennaro, M and Rehman, J and , }, title = {Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37233729}, issn = {2050-084X}, support = {K08 HL141623/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Disease Progression ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {With a global tally of more than 500 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses are key determinants of the severity and outcomes of the initial SARS-CoV-2 infection as well as subsequent PASC. The complexity of the innate and adaptive immune responses in the acute and post-acute period requires in-depth mechanistic analyses to identify specific molecular signals as well as specific immune cell populations which promote PASC pathogenesis. In this review, we examine the current literature on mechanisms of immune dysregulation in severe COVID-19 and the limited emerging data on the immunopathology of PASC. While the acute and post-acute phases may share some parallel mechanisms of immunopathology, it is likely that PASC immunopathology is quite distinct and heterogeneous, thus requiring large-scale longitudinal analyses in patients with and without PASC after an acute SARS-CoV-2 infection. By outlining the knowledge gaps in the immunopathology of PASC, we hope to provide avenues for novel research directions that will ultimately lead to precision therapies which restore healthy immune function in PASC patients.}, } @article {pmid37231313, year = {2023}, author = {Shi, Y and Strobl, R and Apfelbacher, C and Bahmer, T and Geisler, R and Heuschmann, P and Horn, A and Hoven, H and Keil, T and Krawczak, M and Krist, L and Lemhöfer, C and Lieb, W and Lorenz-Depiereux, B and Mikolajczyk, R and Montellano, FA and Reese, JP and Schreiber, S and Skoetz, N and Störk, S and Vehreschild, JJ and Witzenrath, M and Grill, E and , }, title = {Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS‑CoV‑2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort.}, journal = {Infection}, volume = {51}, number = {6}, pages = {1679-1694}, pmid = {37231313}, issn = {1439-0973}, support = {202108140048//China Scholarship Council/ ; }, mesh = {Adult ; Humans ; Female ; Middle Aged ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Prospective Studies ; Retrospective Studies ; Risk Factors ; }, abstract = {PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free.

METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free.

RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection.

CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.}, } @article {pmid37230958, year = {2023}, author = {Meagher, T}, title = {Long Covid - Into the Third Year.}, journal = {Journal of insurance medicine (New York, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.17849/insm-50-1-1-5.1}, pmid = {37230958}, issn = {0743-6661}, abstract = {As the COVID-19 pandemic reaches the end of its third year, and as COVID-related mortality in North America wanes, long Covid and its disabling symptoms are attracting more attention. Some individuals report symptoms lasting more than 2 years, and a subset report continuing disability. This article will provide an update on long Covid, with a particular focus on disease prevalence, disability, symptom clustering and risk factors. It will also discuss the longer-term outlook for individuals with long Covid.}, } @article {pmid37230736, year = {2024}, author = {Clauw, DJ and Calabrese, L}, title = {Rheumatology and Long COVID: lessons from the study of fibromyalgia.}, journal = {Annals of the rheumatic diseases}, volume = {83}, number = {2}, pages = {136-138}, pmid = {37230736}, issn = {1468-2060}, mesh = {Humans ; *Fibromyalgia/epidemiology/therapy ; *Rheumatology ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/epidemiology ; }, abstract = {Rheumatology, such as other subspecialties, has both a unique perspective to offer as well as an evolving role to play in the global COVID-19 pandemic. Our field has already contributed meaningfully to the development and repurposing of many of the immune-based therapeutics which are now standard treatments for severe forms of the disease as well as to the understanding of the epidemiology, risk factors and natural history of COVID-19 in immune-mediated inflammatory diseases. Still in evolution is our potential to contribute to burgeoning research efforts in the next phase of the pandemic: the syndrome of postacute sequelae of COVID-19 or Long COVID. While our field brings many assets to the study of Long COVID including our expertise in the investigation of chronic inflammation and autoimmunity, our Viewpoint focuses on the strong similarities between fibromyalgia (FM) and Long COVID. While one can speculate on how embracing and confident practising rheumatologists already are regarding these interrelationships, we assert that in the emerging field of Long COVID the potential lessons from the field of fibromyalgia care and research have been underappreciated and marginalised and most importantly now deserve a critical appraisal.}, } @article {pmid37230401, year = {2025}, author = {Faghy, MA and Ashton, RE and Skipper, L and Kane, B}, title = {Long COVID - Integrated Approaches to Chronic Disease Management?.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {88-90}, doi = {10.1016/j.amjmed.2023.04.037}, pmid = {37230401}, issn = {1555-7162}, } @article {pmid37229071, year = {2023}, author = {Rahman, A and Ikram, MT and Arif, A and Khan, BD and Azam, KU and Fida, MS and Rahim, AK and Khan, MS and Mushtaq, MH and Fida, R and Yunus, H and Khan, MD}, title = {Prevalence and difference of COVID-19 symptoms, post-COVID conditions and duration of illness among the vaccinated and unvaccinated population: a cross-sectional study in Peshawar.}, journal = {Annals of medicine and surgery (2012)}, volume = {85}, number = {5}, pages = {1678-1684}, pmid = {37229071}, issn = {2049-0801}, abstract = {UNLABELLED: Studies on coronavirus disease 2019 (COVID-19) symptoms, post-coronavirus disease (COVID) conditions, and vaccination outcomes in Pakistan are limited and inconsistent. The study investigated differences in symptoms and post-COVID conditions between vaccinated and unvaccinated individuals and the impact of vaccination on illness duration based on existing literature.

METHODS: The study was a 3-month cross-sectional study conducted in Peshawar, Pakistan. It targeted individuals aged 16 and above who had contracted COVID-19 at least once during the recent pandemic, regardless of gender, and confirmed through reverse transcriptase polymerase chain reaction testing. The sample size was 250, determined using the WHO sample size calculator. Data were collected through questionnaires after obtaining verbal consent and analyzed using IBM SPSS version 26, taking into account their vaccination status along with other important variables.

RESULTS: Among the 250 respondents, 143 (57.2%) were unvaccinated, while 107 (42.8%) were vaccinated at the time of contracting COVID-19. Unvaccinated subjects developed a greater variety of symptoms that lasted for longer durations (P<0.001) with symptoms like dyspnea [55 (38.5%, P=0.011)], anosmia [76 (53.1%, P=0.001)], and chest pain [24 (16.8%, P=0.029)] occurring at greater percentages. Sixty-one (42.7%) unvaccinated subjects reported post-COVID conditions as opposed to 29 (27.1%) among the vaccinated group [P=0.011; odds ratio (OR)=0.5; 95% CI=0.29-0.86].

CONCLUSION: The study found that COVID-19 vaccination can reduce the duration and frequency of symptoms, as well as post-COVID conditions. This is the first research of its kind conducted in Peshawar, Pakistan, and may serve as a foundation for future research in this demographic.}, } @article {pmid37228606, year = {2023}, author = {Berezhnoy, G and Bissinger, R and Liu, A and Cannet, C and Schäfer, H and Kienzle, K and Bitzer, M and Häberle, H and Göpel, S and Trautwein, C and Singh, Y}, title = {Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1144224}, pmid = {37228606}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Cytokines ; SARS-CoV-2 ; Triglycerides ; Proteomics ; Inflammation ; Chemokines ; Syndrome ; Apolipoproteins ; Lipoproteins ; }, abstract = {BACKGROUND: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course.

METHODS: This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). [1]H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes.

RESULTS: Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients.

CONCLUSION: The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.}, } @article {pmid37228290, year = {2023}, author = {Cruz, T and Mendoza, N and Lledó, GM and Perea, L and Albacar, N and Agustí, A and Sellares, J and Sibila, O and Faner, R}, title = {Persistence of a SARS-CoV-2 T-cell response in patients with long COVID and lung sequelae after COVID-19.}, journal = {ERJ open research}, volume = {9}, number = {3}, pages = {}, pmid = {37228290}, issn = {2312-0541}, abstract = {1 year after an acute COVID-19 episode, patients with either lung sequelae or long COVID show a stronger SARS-CoV-2-specific T-cell response than fully recovered individuals, suggesting persistent cell stimulation by residual viral reservoirs https://bit.ly/40bPZm7.}, } @article {pmid37227000, year = {2024}, author = {Schilling, C and Nieters, A and Schredl, M and Peter, RS and Rothenbacher, D and Brockmann, SO and Göpel, S and Kindle, G and Merle, U and Steinacker, JM and Kern, W and , }, title = {Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19.}, journal = {Journal of sleep research}, volume = {33}, number = {2}, pages = {e13949}, doi = {10.1111/jsr.13949}, pmid = {37227000}, issn = {1365-2869}, support = {MR/S028188/1//Baden-Württemberg Federal State Ministry of Science and Art/ ; //German pension fund ("Deutsche Rentenversicherung") Baden-Württemberg/ ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Disease Progression ; *Sleep Wake Disorders/complications/epidemiology ; }, abstract = {Several months after COVID-19 many individuals still report persisting symptoms, the so-called 'post-COVID-19 syndrome'. An immunological dysfunction is one of the main pathophysiological hypotheses. As sleep is central to the functioning of the immune system, we investigated whether self-reported pre-existing sleep disturbance might be an independent risk factor for the development of post-COVID-19 syndrome. A total of 11,710 participants of a cross-sectional survey (all tested positive for severe acute respiratory syndrome coronavirus-2) were classified into probable post-COVID-19 syndrome, an intermediate group, and unaffected participants at an average of 8.5 months after infection. The case definition was based on newly occurring symptoms of at least moderate severity and ≥20% reduction in health status and/or working capacity. Unadjusted and adjusted odds ratios were calculated to investigate the association between pre-existing sleep disturbances and subsequent development of post-COVID-19 syndrome while controlling for a variety of demographic, lifestyle, and health factors. Pre-existing sleep disturbances were found to be an independent predictor of subsequent probable post-COVID-19 syndrome (adjusted odds ratio 2.7, 95% confidence interval 2.27-3.24). Sleep disturbances as part of the post-COVID-19 syndrome were reported by more than half of the participants and appeared to be a new symptom and to occur independent of a mood disorder in most cases. Recognition of disturbed sleep as an important risk factor for post-COVID-19 syndrome should promote improved clinical management of sleep disorders in the context of COVID-19. Further, it may stimulate further research on the effect of improving sleep on the prognosis of COVID-19 long-term sequelae and other post-viral conditions.}, } @article {pmid37226170, year = {2023}, author = {Bogale, KA and Zeru, T and Tarkegn, M and Balew, M and Worku, M and Asrat, A and Adamu, A and Mulu, Y and Getachew, A and Ambaw, F}, title = {Awareness and care seeking for long COVID symptoms among Coronavirus disease survivors in Bahir Dar City, Northwest Ethiopia: phenomenological study.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {941}, pmid = {37226170}, issn = {1471-2458}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Ethiopia ; *COVID-19/epidemiology/therapy ; Behavior Therapy ; Cough ; }, abstract = {BACKGROUND: Corona Virus Disease (COVID-19) has long-term sequels that persisted for months to years and manifested with a spectrum of signs and symptoms. Presentations of long COVID-19 symptoms are heterogeneous, vary from person to person, and can reach up to over 200 symptoms. Limited studies are conducted on the awareness of long COVID-19. So, this study aimed to explore the awareness about and care seeking for long COVID-19 symptoms among COVID survivors in Bahir Dar City in 2022.

METHODS: A qualitative study with a phenomenological design was used. Participants of the study were individuals who survived five months or longer after they tested positive for COVID-19 in Bahir Dar city. Individuals were selected purposively. An in-depth interview guide was prepared and used to collect the data. Open Cod 4.03 software was used for coding and synthesizing. Thematic analysis was used to analyze the transcripts.

RESULTS: The themes emerged from the data were awareness, experience of symptoms and their effects, and care practices of long COVID-19. Although only one participant mentioned the common symptoms of long COVID-19 the survivors experienced general, respiratory, cardiac, digestive, neurological, and other symptoms. These symptoms include rash, fatigue fever, cough, palpitations, shortness of breath, chest pain, and abdominal pain, loss of concentration, loss of smell, sleep disorder, depression, joint and muscle pain. These symptoms brought various physical and psychosocial effects. The majority of the respondents described that long COVID-19 symptoms will go off by themselves. To alleviate the problems some of the participants had taken different measures including medical care, homemade remedies, spiritual solutions, and lifestyle modification.

CONCLUSIONS: The result of this study revealed that participants have a significant deficit of awareness about the common symptoms, risk groups, and communicability of Long COVID. However, they experienced the majority of the common symptoms of Long COVID. To alleviate the problems, they had taken different measures including medical care, homemade remedies, spiritual solutions, and lifestyle modification.}, } @article {pmid37226033, year = {2023}, author = {Nouraeinejad, A}, title = {The functional and structural changes in the hippocampus of COVID-19 patients.}, journal = {Acta neurologica Belgica}, volume = {123}, number = {4}, pages = {1247-1256}, pmid = {37226033}, issn = {2240-2993}, mesh = {Humans ; *COVID-19 ; *Alzheimer Disease ; Hippocampus ; Learning ; Memory Disorders ; }, abstract = {Since the hippocampus is predominantly susceptible to injuries caused by COVID-19, there are increasing data indicating the likelihood of post-infection memory loss and quickening neurodegenerative disorders, such as Alzheimer's disease. This is due to the fact that the hippocampus has imperative functions in spatial and episodic memory as well as learning. COVID-19 activates microglia in the hippocampus and induces a CNS cytokine storm, leading to loss of hippocampal neurogenesis. The functional and structural changes in the hippocampus of COVID-19 patients can explain neuronal degeneration and reduced neurogenesis in the human hippocampus. This will open a window to explain memory and cognitive dysfunctions in "long COVID" through the resultant loss of hippocampal neurogenesis.}, } @article {pmid37223650, year = {2023}, author = {Loftis, JM and Firsick, E and Shirley, K and Adkins, JL and Le-Cook, A and Sano, E and Hudson, R and Moorman, J}, title = {Inflammatory and mental health sequelae of COVID-19.}, journal = {Comprehensive psychoneuroendocrinology}, volume = {15}, number = {}, pages = {100186}, pmid = {37223650}, issn = {2666-4976}, support = {I01 BX002061/BX/BLRD VA/United States ; I01 BX005428/BX/BLRD VA/United States ; }, abstract = {The COVID-19 pandemic has caused significant negative consequences to mental health. Increased inflammatory factors and neuropsychiatric symptoms, such as cognitive impairment ("brain fog"), depression, and anxiety are associated with long COVID [post-acute sequelae of SARS-CoV-2 infection (PASC), termed neuro-PASC]. The present study sought to examine the role of inflammatory factors as predictors of neuropsychiatric symptom severity in the context of COVID-19. Adults (n = 52) who tested negative or positive for COVID-19 were asked to complete self-report questionnaires and to provide blood samples for multiplex immunoassays. Participants who tested negative for COVID-19 were assessed at baseline and at a follow-up study visit (∼4 weeks later). Individuals without COVID-19 reported significantly lower PHQ-4 scores at the follow-up visit, as compared to baseline (p = 0.03; 95% CI-1.67 to -0.084). Individuals who tested positive for COVID-19 and experienced neuro-PASC had PHQ-4 scores in the moderate range. The majority of people with neuro-PASC reported experiencing brain fog (70% vs. 30%). Those with more severe COVID-19 had significantly higher PHQ-4 scores, as compared to those with mild disease (p = 0.008; 95% CI 1.32 to 7.97). Changes in neuropsychiatric symptom severity were accompanied by alterations in immune factors, particularly monokine induced by gamma interferon (IFN-γ) (MIG, a. k.a. CXCL9). These findings add to the growing evidence supporting the usefulness of circulating MIG levels as a biomarker reflecting IFN-γ production, which is important because individuals with neuro-PASC have elevated IFN-γ responses to internal SARS-CoV-2 proteins.}, } @article {pmid37223439, year = {2023}, author = {Finnigan, LEM and Cassar, MP and Koziel, MJ and Pradines, J and Lamlum, H and Azer, K and Kirby, D and Montgomery, H and Neubauer, S and Valkovič, L and Raman, B}, title = {Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study.}, journal = {EClinicalMedicine}, volume = {59}, number = {}, pages = {101946}, pmid = {37223439}, issn = {2589-5370}, abstract = {BACKGROUND: 'Long COVID' describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID.

METHODS: Patients with fatigue-dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical-based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two-week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by [31]P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849.

FINDINGS: Between December 15th 2021, and May 23th 2022, 60 participants were screened, and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] -4.30, 95% confidence interval (95% CI) -7.14, -1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation.

INTERPRETATION: Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there were significant improvements in fatigue-based symptoms among patients living with Long COVID following a four-week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID.

FUNDING: Axcella Therapeutics.}, } @article {pmid37220832, year = {2025}, author = {Bailey, J and Lavelle, B and Miller, J and Jimenez, M and Lim, PH and Orban, ZS and Clark, JR and Tomar, R and Ludwig, A and Ali, ST and Lank, GK and Zielinski, A and Mylvaganam, R and Kalhan, R and El Muayed, M and Mutharasan, RK and Liotta, EM and Sznajder, JI and Davidson, C and Koralnik, IJ and Sala, MA and , }, title = {Multidisciplinary Center Care for Long COVID Syndrome-A Retrospective Cohort Study.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {108-120}, pmid = {37220832}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/therapy/epidemiology/complications ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Aged ; SARS-CoV-2 ; Adult ; Chicago/epidemiology ; Quality of Life ; Patient Care Team ; }, abstract = {BACKGROUND: Persistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed "long COVID" or "post-acute sequelae of SARS-CoV-2 infection." The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers.

METHODS: We performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19.

RESULTS: We evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/916 (81%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results.

CONCLUSIONS: The experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations.}, } @article {pmid37219466, year = {2023}, author = {Chirumbolo, S and Tirelli, U}, title = {Post-COVID or long-COVID? That is the question.}, journal = {Polish archives of internal medicine}, volume = {133}, number = {5}, pages = {}, doi = {10.20452/pamw.16506}, pmid = {37219466}, issn = {1897-9483}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37219465, year = {2023}, author = {Lippi, G and Sanchis-Gomar, F and Henry, BM}, title = {Post-COVID or long-COVID? That is the question. Authors' reply.}, journal = {Polish archives of internal medicine}, volume = {133}, number = {5}, pages = {}, doi = {10.20452/pamw.16507}, pmid = {37219465}, issn = {1897-9483}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37218289, year = {2023}, author = {Pfaff, ER and Girvin, AT and Crosskey, M and Gangireddy, S and Master, H and Wei, WQ and Kerchberger, VE and Weiner, M and Harris, PA and Basford, M and Lunt, C and Chute, CG and Moffitt, RA and Haendel, M and , }, title = {De-black-boxing health AI: demonstrating reproducible machine learning computable phenotypes using the N3C-RECOVER Long COVID model in the All of Us data repository.}, journal = {Journal of the American Medical Informatics Association : JAMIA}, volume = {30}, number = {7}, pages = {1305-1312}, pmid = {37218289}, issn = {1527-974X}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; UM1 TR004404/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; R01 GM139891/GM/NIGMS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; OT2 OD026556/OD/NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; K01 HL157755/HL/NHLBI NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Electronic Health Records ; Post-Acute COVID-19 Syndrome ; Reproducibility of Results ; *Boxing ; *COVID-19 ; *Population Health ; Machine Learning ; Phenotype ; }, abstract = {Machine learning (ML)-driven computable phenotypes are among the most challenging to share and reproduce. Despite this difficulty, the urgent public health considerations around Long COVID make it especially important to ensure the rigor and reproducibility of Long COVID phenotyping algorithms such that they can be made available to a broad audience of researchers. As part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, researchers with the National COVID Cohort Collaborative (N3C) devised and trained an ML-based phenotype to identify patients highly probable to have Long COVID. Supported by RECOVER, N3C and NIH's All of Us study partnered to reproduce the output of N3C's trained model in the All of Us data enclave, demonstrating model extensibility in multiple environments. This case study in ML-based phenotype reuse illustrates how open-source software best practices and cross-site collaboration can de-black-box phenotyping algorithms, prevent unnecessary rework, and promote open science in informatics.}, } @article {pmid37217883, year = {2023}, author = {Mondoni, M and Rinaldo, RF and Cefalo, J and Saderi, L and Vigo, B and Carlucci, P and Tirelli, C and Cariboni, U and Santus, P and Centanni, S and Sotgiu, G}, title = {Bronchoscopy in the post-acute phase of COVID-19: an observational study.}, journal = {BMC pulmonary medicine}, volume = {23}, number = {1}, pages = {178}, pmid = {37217883}, issn = {1471-2466}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Retrospective Studies ; *Tracheal Stenosis/etiology ; Bronchoscopy/methods ; Trachea ; Disease Progression ; }, abstract = {BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19.

METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled.

RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer.

CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.}, } @article {pmid37217645, year = {2023}, author = {Zanin, A and Amah, G and Chakroun, S and Testard, P and Faucher, A and Le, TYV and Slama, D and Le Baut, V and Lozeron, P and Salmon, D and Kubis, N}, title = {Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8251}, pmid = {37217645}, issn = {2045-2322}, mesh = {Humans ; Female ; Adult ; *COVID-19 ; SARS-CoV-2 ; Autonomic Nervous System ; *Primary Dysautonomias/diagnosis ; Cardiovascular Physiological Phenomena ; Heart Rate/physiology ; }, abstract = {Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.}, } @article {pmid37217471, year = {2023}, author = {Brannock, MD and Chew, RF and Preiss, AJ and Hadley, EC and Redfield, S and McMurry, JA and Leese, PJ and Girvin, AT and Crosskey, M and Zhou, AG and Moffitt, RA and Funk, MJ and Pfaff, ER and Haendel, MA and Chute, CG and , and , }, title = {Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {2914}, pmid = {37217471}, issn = {2041-1723}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; }, mesh = {United States/epidemiology ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Cohort Studies ; SARS-CoV-2 ; Vaccination ; }, abstract = {Long COVID, or complications arising from COVID-19 weeks after infection, has become a central concern for public health experts. The United States National Institutes of Health founded the RECOVER initiative to better understand long COVID. We used electronic health records available through the National COVID Cohort Collaborative to characterize the association between SARS-CoV-2 vaccination and long COVID diagnosis. Among patients with a COVID-19 infection between August 1, 2021 and January 31, 2022, we defined two cohorts using distinct definitions of long COVID-a clinical diagnosis (n = 47,404) or a previously described computational phenotype (n = 198,514)-to compare unvaccinated individuals to those with a complete vaccine series prior to infection. Evidence of long COVID was monitored through June or July of 2022, depending on patients' data availability. We found that vaccination was consistently associated with lower odds and rates of long COVID clinical diagnosis and high-confidence computationally derived diagnosis after adjusting for sex, demographics, and medical history.}, } @article {pmid37217235, year = {2023}, author = {George, AS and Lopes, CA and Vijayasingham, L and Mothupi, MC and Musizvingoza, R and Mishra, G and Stevenson, J and Remme, M}, title = {A shared agenda for gender and COVID-19 research: priorities based on broadening engagement in science.}, journal = {BMJ global health}, volume = {8}, number = {5}, pages = {}, pmid = {37217235}, issn = {2059-7908}, mesh = {Male ; Humans ; Female ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Lactation ; Public Policy ; }, abstract = {While the acute and collective crisis from the pandemic is over, an estimated 2.5 million people died from COVID-19 in 2022, tens of millions suffer from long COVID and national economies still reel from multiple deprivations exacerbated by the pandemic. Sex and gender biases deeply mark these evolving experiences of COVID-19, impacting the quality of science and effectiveness of the responses deployed. To galvanise change by strengthening evidence-informed inclusion of sex and gender in COVID-19 practice, we led a virtual collaboration to articulate and prioritise gender and COVID-19 research needs. In addition to standard prioritisation surveys, feminist principles mindful of intersectional power dynamics underpinned how we reviewed research gaps, framed research questions and discussed emergent findings. The collaborative research agenda-setting exercise engaged over 900 participants primarily from low/middle-income countries in varied activities. The top 21 research questions included the importance of the needs of pregnant and lactating women and information systems that enable sex-disaggregated analysis. Gender and intersectional aspects to improving vaccine uptake, access to health services, measures against gender-based violence and integrating gender in health systems were also prioritised. These priorities are shaped by more inclusive ways of working, which are critical for global health as it faces further uncertainties in the aftermath of COVID-19. It remains imperative to address the basics in gender and health (sex-disaggregated data and sex-specific needs) and also advance transformational goals to advance gender justice across health and social policies, including those related to global research.}, } @article {pmid37217233, year = {2023}, author = {Saniasiaya, J}, title = {Vestibular migraine: a manifestation of long COVID syndrome in children.}, journal = {BMJ case reports}, volume = {16}, number = {5}, pages = {}, pmid = {37217233}, issn = {1757-790X}, mesh = {Adolescent ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Vertigo/etiology ; *Migraine Disorders/diagnosis/etiology ; Headache/etiology ; }, abstract = {Long COVID-19 syndrome has been reported among children and adolescents following COVID-19 recovery. Among them, notable symptoms include myalgia, insomnia, loss of smell and headache. Yet, novel manifestations are being discovered daily. Herein, we report two cases of vestibular migraine post-COVID-19 involving two children who presented with vestibular migraine symptoms following COVID-19 infection and their management. Children post-COVID-19 should be thoroughly evaluated for vestibular migraine symptoms so they can be managed promptly. This is the first article to report vestibular migraine as a manifestation of long COVID-19 syndrome.}, } @article {pmid37216955, year = {2023}, author = {Singh, SJ and Baldwin, MM and Daynes, E and Evans, RA and Greening, NJ and Jenkins, RG and Lone, NI and McAuley, H and Mehta, P and Newman, J and Novotny, P and Smith, DJF and Stanel, S and Toshner, M and Brightling, CE}, title = {Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {709-725}, pmid = {37216955}, issn = {2213-2619}, support = {MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Dyspnea/etiology/therapy ; *Pulmonary Fibrosis ; Disease Progression ; }, abstract = {Although the exact prevalence of post-COVID-19 condition (also known as long COVID) is unknown, more than a third of patients with COVID-19 develop symptoms that persist for more than 3 months after SARS-CoV-2 infection. These sequelae are highly heterogeneous in nature and adversely affect multiple biological systems, although breathlessness is a frequently cited symptom. Specific pulmonary sequelae, including pulmonary fibrosis and thromboembolic disease, need careful assessment and might require particular investigations and treatments. COVID-19 outcomes in people with pre-existing respiratory conditions vary according to the nature and severity of the respiratory disease and how well it is controlled. Extrapulmonary complications such as reduced exercise tolerance and frailty might contribute to breathlessness in post-COVID-19 condition. Non-pharmacological therapeutic options, including adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management, might help to attenuate breathlessness in people with post-COVID-19 condition. Further research is needed to understand the origins and course of respiratory symptoms and to develop effective therapeutic and rehabilitative strategies.}, } @article {pmid37216631, year = {2023}, author = {Hachinski, V and Krishnamoorthy, E and Kuey, L and Kirmayer, LJ}, title = {Brain health and mental health: Common vascular risk factors and practical implications.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {19}, number = {9}, pages = {4248-4251}, doi = {10.1002/alz.13153}, pmid = {37216631}, issn = {1552-5279}, mesh = {Humans ; Mental Health ; *Mental Disorders/epidemiology ; Brain ; *Stroke/complications ; Risk Factors ; }, abstract = {The pandemic dramatized the close links among cognitive, mental, and social health; a change in one reflects others. This realization offers the opportunity to bridge the artificial separation of brain and mental health, as brain disorders have behavioral consequences and behavioral disorders affect the brain. The leading causes of mortality and disability, namely stroke, heart disease, and dementia, share the same risk and protective factors. It is emerging that bipolar disorders, obsessive compulsive disorders, and some depressions share these risk factors, allowing their joint prevention through a holistic life span approach. We need to learn to focus on the whole patient, not simply on a dysfunctional organ or behavior to mitigate or prevent the major neurological and mental disorders by fostering an integrated approach to brain and mental health and addressing the common, treatable risk factors.}, } @article {pmid37216305, year = {2023}, author = {Del Carpio-Orantes, L and Aguilar-Silva, A}, title = {[Intertwined long COVID theories to explain its etiopathogenesis].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {61}, number = {3}, pages = {256-257}, pmid = {37216305}, issn = {2448-5667}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Thrombosis/etiology ; }, abstract = {This editorial lists the main current theories on long COVID, such as the theory of viral persistence and the one of immunothrombosis associated with deregulation of the immune system; it is discussed as well their interrelation, which finally explains the etiopathogenesis and physiopathology of this new syndrome that afflicts the survivors of COVID-19; it is also discussed the link between viral persistence with the formation of amyloid microthrombi based on the hypothesis that the spike protein causes amyloidogenesis, inducing organic chronic damage that will characterize long COVID.}, } @article {pmid37216202, year = {2023}, author = {}, title = {COVID-19 update: Metformin to prevent long COVID?.}, journal = {The Medical letter on drugs and therapeutics}, volume = {65}, number = {1677}, pages = {87-88}, doi = {10.58347/tml.2023.1677e}, pmid = {37216202}, issn = {1523-2859}, mesh = {Humans ; *Metformin/therapeutic use ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hypoglycemic Agents/adverse effects ; SARS-CoV-2 ; Ivermectin ; }, } @article {pmid37215236, year = {2023}, author = {SeyedAlinaghi, S and Bagheri, A and Razi, A and Mojdeganlou, P and Mojdeganlou, H and Afsahi, AM and Afzalian, A and Paranjkhoo, P and Shahidi, R and Mirzapour, P and Pashaei, Z and Habibi, MA and Shahbazi, P and Nooralioghli Parikhani, S and Farizani Gohari, NS and Popoola, Y and Mehraeen, E and Hackett, D}, title = {Late Complications of COVID-19; An Umbrella Review on Current Systematic Reviews.}, journal = {Archives of academic emergency medicine}, volume = {11}, number = {1}, pages = {e28}, pmid = {37215236}, issn = {2645-4904}, abstract = {INTRODUCTION: Several clinical manifestations have been discovered for COVID-19 since the emergence of SARS-CoV-2, which can be classified into early, medium, and long-term complications. However, late complications can be present after recovery from acute COVID-19 illness. The present study aims to comprehensively review the available evidence of late complications related to COVID-19.

METHOD: A search was conducted, using keywords, through electronic databases, which included Scopus, Web of Science, PubMed, and Embase up to August 29, 2022. Study selection was performed according to a strict inclusion and exclusion criteria. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist was followed, and studies were appraised using the National Institute of Health (NIH) quality assessment and risk of bias tool.

RESULTS: In total, 50 studies were included, and nine distinct COVID-19 late complication categories were identified. A review of these studies revealed that neurologic and psychiatric (n=41), respiratory (n=27), musculoskeletal and rheumatologic (n=22), cardiovascular (n=9), and hepatic and gastrointestinal (n=6) complications were the most prevalent complications of long COVID-19.

CONCLUSION: Almost all human body systems are affected by late complications of COVID-19 with different severity and prevalence. Fatigue and some other neuropsychiatric symptoms are the most common late complications among long COVID-19 patients. Respiratory symptoms including dyspnea (during exercise), cough, and chest tightness were the next most prevalent long-term complications of COVID-19. Since these complications are persistent and late, being aware of the signs and symptoms is essential for the healthcare providers and patients.}, } @article {pmid37214806, year = {2023}, author = {Gross, R and Thaweethai, T and Rosenzweig, EB and Chan, J and Chibnik, LB and Cicek, MS and Elliott, AJ and Flaherman, VJ and Foulkes, AS and Witvliet, MG and Gallagher, R and Gennaro, ML and Jernigan, TL and Karlson, EW and Katz, SD and Kinser, PA and Kleinman, LC and Lamendola-Essel, MF and Milner, JD and Mohandas, S and Mudumbi, PC and Newburger, JW and Rhee, KE and Salisbury, AL and Snowden, JN and Stein, CR and Stockwell, MS and Tantisira, KG and Thomason, ME and Truong, DT and Warburton, D and Wood, JC and Ahmed, S and Akerlundh, A and Alshawabkeh, AN and Anderson, BR and Aschner, JL and Atz, AM and Aupperle, RL and Baker, FC and Balaraman, V and Banerjee, D and Barch, DM and Baskin-Sommers, A and Bhuiyan, S and Bind, MC and Bogie, AL and Buchbinder, NC and Bueler, E and Bükülmez, H and Casey, BJ and Chang, L and Clark, DB and Clifton, RG and Clouser, KN and Cottrell, L and Cowan, K and D'Sa, V and Dapretto, M and Dasgupta, S and Dehority, W and Dummer, KB and Elias, MD and Esquenazi-Karonika, S and Evans, DN and Faustino, EVS and Fiks, AG and Forsha, D and Foxe, JJ and Friedman, NP and Fry, G and Gaur, S and Gee, DG and Gray, KM and Harahsheh, AS and Heath, AC and Heitzeg, MM and Hester, CM and Hill, S and Hobart-Porter, L and Hong, TKF and Horowitz, CR and Hsia, DS and Huentelman, M and Hummel, KD and Iacono, WG and Irby, K and Jacobus, J and Jacoby, VL and Jone, PN and Kaelber, DC and Kasmarcak, TJ and Kluko, MJ and Kosut, JS and Laird, AR and Landeo-Gutierrez, J and Lang, SM and Larson, CL and Lim, PPC and Lisdahl, KM and McCrindle, BW and McCulloh, RJ and Mendelsohn, AL and Metz, TD and Morgan, LM and Müller-Oehring, EM and Nahin, ER and Neale, MC and Ness-Cochinwala, M and Nolan, SM and Oliveira, CR and Oster, ME and Payne, RM and Raissy, H and Randall, IG and Rao, S and Reeder, HT and Rosas, JM and Russell, MW and Sabati, AA and Sanil, Y and Sato, AI and Schechter, MS and Selvarangan, R and Shakti, D and Sharma, K and Squeglia, LM and Stevenson, MD and Szmuszkovicz, J and Talavera-Barber, MM and Teufel, RJ and Thacker, D and Udosen, MM and Warner, MR and Watson, SE and Werzberger, A and Weyer, JC and Wood, MJ and Yin, HS and Zempsky, WT and Zimmerman, E and Dreyer, BP}, title = {Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37214806}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; U01 DA041117/DA/NIDA NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, abstract = {IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.

CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.

CLINICAL TRIALSGOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.}, } @article {pmid37213637, year = {2023}, author = {Zhang, D and Chung, VC and Chan, DC and Xu, Z and Zhou, W and Tam, KW and Lee, RC and Sit, RW and Mercer, SW and Wong, SY}, title = {Determinants of post-COVID-19 symptoms among adults aged 55 or above with chronic conditions in primary care: data from a prospective cohort in Hong Kong.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1138147}, pmid = {37213637}, issn = {2296-2565}, mesh = {Humans ; Adult ; Female ; Aged ; Male ; *COVID-19/epidemiology ; Hong Kong/epidemiology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Chronic Disease ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Dyspnea/etiology ; Fatigue/etiology ; Primary Health Care ; }, abstract = {BACKGROUND: Primary care patients, especially those with an older age, are one of the most vulnerable populations for post-COVID-19 symptoms. Identifying predictors of post-COVID symptoms can help identify high-risk individuals for preventive care.

METHODS: Out of 977 primary care patients aged 55 years or above with comorbid physical and psychosocial conditions in a prospective cohort in Hong Kong, 207 patients infected in the previous 5-24 weeks were included. The three most common post-COVID-19 symptoms (breathlessness, fatigue, cognitive difficulty), which lasted beyond the 4-week acute infection period, were assessed using items from the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), together with other self-reported symptoms. Multivariable analyses were conducted to identify predictors of post-acute and long COVID-19 symptoms (5-24 weeks after infection).

RESULTS: The 207 participants had a mean age of 70.8 ± 5.7 years, 76.3% were female, and 78.7% had ≥2 chronic conditions. In total, 81.2% reported at least one post-COVID symptom (mean: 1.9 ± 1.3); 60.9, 56.5 and 30.0% reported fatigue, cognitive difficulty, and breathlessness respectively; 46.1% reported at least one other new symptom (such as other respiratory-related symptoms (14.0%), insomnia or poor sleep quality (14.0%), and ear/nose/throat symptoms (e.g., sore throat) (10.1%), etc.). Depression predicted post-COVID-19 fatigue. The female sex predicted cognitive difficulty. Receiving fewer vaccine doses (2 doses vs. 3 doses) was associated with breathlessness. Anxiety predicted a higher overall symptom severity level of the three common symptoms.

CONCLUSION: Depression, the female sex, and fewer vaccine doses predicted post-COVID symptoms. Promoting vaccination and providing intervention to those at high-risk for post-COVID symptoms are warranted.}, } @article {pmid37212320, year = {2023}, author = {Fong, SW and Goh, YS and Torres-Ruesta, A and Chang, ZW and Chan, YH and Neo, VK and Lee, B and Duan, K and Amrun, SN and Yeo, NK and Chen, HV and Tay, MZ and Carissimo, G and , and , and Tan, SY and Leo, YS and Lye, DC and Renia, L and Young, BE and Ng, LFP}, title = {Prolonged inflammation in patients hospitalized for coronavirus disease 2019 (COVID-19) resolves 2 years after infection.}, journal = {Journal of medical virology}, volume = {95}, number = {5}, pages = {e28774}, doi = {10.1002/jmv.28774}, pmid = {37212320}, issn = {1096-9071}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Longitudinal Studies ; Prospective Studies ; Inflammation ; Cytokines ; }, abstract = {Long-term complications from coronavirus disease 2019 (COVID-19) are concerning, as survivors can develop subclinical multiorgan dysfunction. It is unknown if such complications are due to prolonged inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination may reduce sequela. We conducted a prospective longitudinal study on hospitalized patients over 24 months. Clinical symptoms were collected by self-reporting during follow-up, along with blood samples for quantification of inflammatory markers and immune cell frequencies. All patients were given one dose of mRNA vaccine at 12-16 months. Their immune profiles at 12 and 24 months were compared. Approximately 37% and 39% of our patients reported post-COVID-19 symptoms at 12 and 24 months, respectively. The proportion of symptomatic patients with more than one symptom decreased from 69% at 12 months to 56% at 24 months. Longitudinal cytokine profiling revealed a cluster of individuals with persistently high inflammatory cytokine levels 12 months after infection. Patients with prolonged inflammation showed elevated terminally differentiated memory T cells in their blood; 54% had symptoms at 12 months. The majority of inflammatory markers and dysregulated immune cells in vaccinated patients recovered to a healthy baseline at 24 months, even though symptoms persisted. Post-COVID-19 symptoms can linger for 2 years after the initial infection and are associated with prolonged inflammation. Prolonged inflammation in hospitalized patients resolves after 2 years. We define a set of analytes associated with persistent inflammation and presence of symptoms, which could be useful biomarkers for identifying and monitoring high-risk survivors.}, } @article {pmid37211986, year = {2023}, author = {Sung, PS and Sun, CP and Tao, MH and Hsieh, SL}, title = {Inhibition of SARS-CoV-2-mediated thromboinflammation by CLEC2.Fc.}, journal = {EMBO molecular medicine}, volume = {15}, number = {7}, pages = {e16351}, pmid = {37211986}, issn = {1757-4684}, mesh = {Humans ; Mice ; Animals ; SARS-CoV-2 ; *COVID-19 ; Inflammation ; Thromboinflammation ; Post-Acute COVID-19 Syndrome ; *Thrombosis ; Protein Binding ; }, abstract = {Thromboinflammation is the major cause of morbidity and mortality in COVID-19 patients, and post-mortem examination demonstrates the presence of platelet-rich thrombi and microangiopathy in visceral organs. Moreover, persistent microclots were detected in both acute COVID-19 and long COVID plasma samples. However, the molecular mechanism of SARS-CoV-2-induced thromboinflammation is still unclear. We found that the spleen tyrosine kinase (Syk)-coupled C-type lectin member 2 (CLEC2), which was highly expressed in platelets and alveolar macrophages, interacted with the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD) directly. Unlike the thread-like NETs, SARS-CoV-2-induced aggregated NET formation in the presence of wild-type (WT), but not CLEC2-deficient platelets. Furthermore, SARS-CoV-2 spike pseudotyped lentivirus was able to induce NET formation via CLEC2, indicating SARS-CoV-2 RBD engaged CLEC2 to activate platelets to enhance NET formation. Administration of CLEC2.Fc inhibited SARS-CoV-2-induced NET formation and thromboinflammation in AAV-ACE2-infected mice. Thus, CLEC2 is a novel pattern recognition receptor for SARS-CoV-2, and CLEC2.Fc and may become a promising therapeutic agent to inhibit SARS-CoV-2-induced thromboinflammation and reduced the risk of post-acute sequelae of COVID-19 (PASC) in the future.}, } @article {pmid37211198, year = {2024}, author = {Contreras, AM and Newman, DB and Cappelloni, L and Niven, AS and Mueller, MR and Ganesh, R and Squires, RW and Bonikowske, AR and Allison, TG}, title = {Cardiopulmonary testing in long COVID-19 versus non-COVID-19 patients with undifferentiated Dyspnea on exertion.}, journal = {Progress in cardiovascular diseases}, volume = {83}, number = {}, pages = {71-76}, pmid = {37211198}, issn = {1873-1740}, mesh = {Humans ; Female ; *COVID-19/physiopathology/complications/diagnosis ; Male ; *Dyspnea/physiopathology/diagnosis/etiology ; Middle Aged ; *Exercise Test ; *Exercise Tolerance ; Adult ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Physical Exertion ; }, abstract = {BACKGROUND: Dyspnea and fatigue are characteristics of long SARS-CoV-2 (COVID)-19. Cardiopulmonary exercise testing (CPET) can be used to better evaluate such patients.

RESEARCH QUESTION: How significantly and by what mechanisms is exercise capacity impaired in patients with long COVID who are coming to a specialized clinic for evaluation?

STUDY DESIGN AND METHODS: We performed a cohort study using the Mayo Clinic exercise testing database. Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. Statistical comparisons were performed by t-test or Pearson's chi[2] test controlling for age, sex, and beta blocker use where appropriate.

RESULTS: We found 77 patients with long COVID and 766 control patients. Long COVID patients were younger (47 ± 15 vs 50 ± 10 years, P < .01) and more likely female (70% vs 58%, P < .01). The most prominent difference on CPETs was lower percent predicted peak V̇O2 (73 ± 18 vs 85 ± 23%, p < .0001). Autonomic abnormalities (resting tachycardia, CNS changes, low systolic blood pressure) were seen during CPET more commonly in long COVID patients (34 vs 23%, P < .04), while mild pulmonary abnormalities (mild desaturation, limited breathing reserve, elevated V̇E/V̇CO2) during CPET were similar (19% in both groups) with only 1 long COVID patient showing severe impairment.

INTERPRETATION: We identified severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Though mild pulmonary and autonomic impairment were common in long COVID patients, marked limitations were uncommon. We hope our observations help to untangle the physiologic abnormalities responsible for the symptomatology of long COVID.}, } @article {pmid37210757, year = {2023}, author = {Manganotti, P and Michelutti, M and Furlanis, G and Deodato, M and Buoite Stella, A}, title = {Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {151}, number = {}, pages = {83-91}, pmid = {37210757}, issn = {1872-8952}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Electromyography ; *Motor Cortex/physiology ; Neural Inhibition/physiology ; *COVID-19 ; Transcranial Magnetic Stimulation ; Evoked Potentials, Motor/physiology ; *Cognitive Dysfunction/diagnosis ; }, abstract = {OBJECTIVE: Attention, working memory and executive processing have been reported to be consistently impaired in Neuro-Long coronavirus disease (COVID). On the hypothesis of abnormal cortical excitability, we investigated the functional state of inhibitory and excitatory cortical regulatory circuits by single "paired-pulse" transcranial magnetic stimulation (ppTMS) and Short-latency Afferent Inhibition (SAI).

METHODS: We compared clinical and neurophysiological data of 18 Long COVID patients complaining of persistent cognitive impairment with 16 Healthy control (HC) subjects. Cognitive status was evaluated by means of the Montreal Cognitive Assessment (MoCA) and a neuropsychological evaluation of the executive function domain; fatigue was scored by the Fatigue Severity Scale (FSS). Resting motor threshold (RMT), the amplitude of the motor evoked potential (MEP), Short Intra-cortical Inhibition (SICI), Intra-cortical Facilitation (ICF), Long-interval Intracortical Inhibition (LICI) and Short-afferent inhibition (SAI) were investigated over the motor (M1) cortex.

RESULTS: MoCA corrected scores were significantly different between the two groups (p = 0.023). The majority of the patients' performed sub-optimally in the neuropsychological assessment of the executive functions. The majority (77.80%) of the patients reported high levels of perceived fatigue in the FSS. RMT, MEPs, SICI and SAI were not significantly different between the two groups. On the other hand, Long COVID patients showed a reduced amount of inhibition in LICI (p = 0.003) and a significant reduction in ICF (p < 0.001).

CONCLUSIONS: Neuro-Long COVID patients performing sub-optimally in the executive functions showed a reduction of LICI related to GABAb inhibition and a reduction of ICF related to glutamatergic regulation. No alteration in cholinergic circuits was found.

SIGNIFICANCE: These findings can help to better understand the neurophysiological characteristics of Neuro-Long COVID, and in particular, motor cortex regulation in people with "brain fog".}, } @article {pmid37209261, year = {2024}, author = {Kole, C and Stefanou, Ε and Karvelas, N and Schizas, D and Toutouzas, KP}, title = {Acute and Post-Acute COVID-19 Cardiovascular Complications: A Comprehensive Review.}, journal = {Cardiovascular drugs and therapy}, volume = {38}, number = {5}, pages = {1017-1032}, pmid = {37209261}, issn = {1573-7241}, mesh = {Humans ; *COVID-19/complications/epidemiology/therapy ; *Cardiovascular Diseases/epidemiology/etiology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Acute Disease ; }, abstract = {PURPOSE OF REVIEW: The risk of cardiovascular complications due to SARS-CoV-2 are significantly increased within the first 6 months of the infection. Patients with COVID-19 have an increased risk of death, and there is evidence that many may experience a wide range of post-acute cardiovascular complications. Our work aims to provide an update on current clinical aspects of diagnosis and treatment of cardiovascular manifestations during acute and long-term COVID-19.

RECENT FINDINGS: SARS-CoV-2 has been shown to be associated with increased incidence of cardiovascular complications such as myocardial injury, heart failure, and dysrhythmias, as well as coagulation abnormalities not only during the acute phase but also beyond the first 30 days of the infection, associated with high mortality and poor outcomes. Cardiovascular complications during long-COVID-19 were found regardless of comorbidities such as age, hypertension, and diabetes; nevertheless, these populations remain at high risk for the worst outcomes during post-acute COVID-19. Emphasis should be given to the management of these patients. Treatment with low-dose oral propranolol, a beta blocker, for heart rate management may be considered, since it was found to significantly attenuate tachycardia and improve symptoms in postural tachycardia syndrome, while for patients on ACE inhibitors or angiotensin-receptor blockers (ARBs), under no circumstances should these medications be withdrawn. In addition, in patients at high risk after hospitalization due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. In this work we provide a comprehensive review on acute and post-acute COVID-19 cardiovascular complications, symptomatology, and pathophysiology mechanisms. We also discuss therapeutic strategies for these patients during acute and long-term care and highlight populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease have worse outcomes during acute SARS-CoV-2 infection and are more likely to develop cardiovascular complications during long-COVID-19.}, } @article {pmid37209039, year = {2023}, author = {D'Souza, F and Buzzetti, R and Pozzilli, P}, title = {Diabetes, COVID-19, and questions unsolved.}, journal = {Diabetes/metabolism research and reviews}, volume = {39}, number = {5}, pages = {e3666}, doi = {10.1002/dmrr.3666}, pmid = {37209039}, issn = {1520-7560}, mesh = {Humans ; COVID-19 Vaccines ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus/epidemiology ; *Hyperglycemia ; Disease Progression ; }, abstract = {Recent evidence suggests a role for Diabetes Mellitus in adverse outcomes from COVID-19 infection; yet the underlying mechanisms are not clear. Moreover, attention has turned to prophylactic vaccination to protect the population from COVID-19-related illness and mortality. We performed a comprehensive peer-reviewed literature search on an array of key terms concerning diabetes and COVID-19 seeking to address the following questions: 1. What role does diabetes play as an accelerator for adverse outcomes in COVID-19?; 2. What mechanisms underlie the differences in outcomes seen in people with diabetes?; 3. Are vaccines against COVID-19 efficacious in people with diabetes? The current literature demonstrates that diabetes is associated with an increased risk of adverse outcomes from COVID-19 infection, and post-COVID sequelae. Potential mechanisms include dysregulation of Angiotensin Converting Enzyme 2, Furin, CD147, and impaired immune cell responses. Hyperglycaemia is a key exacerbator of these mechanisms. Limited studies are available on COVID-19 vaccination in people with diabetes; however, the current literature suggests that vaccination is protective against adverse outcomes for this population. In summary, people with diabetes are a high-risk group that should be prioritised in vaccination efforts. Glycaemic optimisation is paramount to protecting this group from COVID-19-associated risk. Unsolved questions remain as to the molecular mechanisms underlying the adverse outcomes seen in people with diabetes; the functional impact of post-COVID symptoms on people with diabetes, their persistence, and management; how long-term vaccine efficacy is affected by diabetes, and the antibody levels that confer protection from adverse outcomes in COVID-19.}, } @article {pmid37208435, year = {2023}, author = {Mohtasham-Amiri, Z and Keihanian, F and Rad, EH and Shakib, RJ and Vahed, LK and Kouchakinejad-Eramsadati, L and Rezvani, SM and Nikkar, R}, title = {Long- COVID and general health status in hospitalized COVID-19 survivors.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8116}, pmid = {37208435}, issn = {2045-2322}, mesh = {Humans ; Adult ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Aggression ; Survivors ; Health Status ; }, abstract = {Despite advances in clinical research, the long-term effects of COVID-19 on patients are not clear. Many studies revealed persistent long-term signs and symptoms. In a survey study, 259 hospitalized confirmed COVID-19 patients between 18 and 59 years were interviewed. Demographic characteristics and complaints were studied through telephone interviews. Any patient-reported symptoms that continued or developed from 4 weeks up to 12 weeks after the onset of the disease were recorded only if they did not exist prior to infection. The 12-Item General Health Questionnaire was used for screening and assessing mental symptoms and psychosocial well-being. The mean age of participants was 43.8 ± 9.9 years. About 37% had at least one underlying disease. 92.5% showed ongoing symptoms that the most prevalent complications were hair loss (61.4%), fatigue (54.1%), shortness of breath (40.2%), altered smell (34.4%), and aggression (34.4%), respectively. In terms of factors affecting patients' complaints, there were significant differences between age, sex, and underlying disease with long-remaining complications. This study shows a high rate of long COVID-19 conditions that should be considered by physicians, policymakers, and managers.}, } @article {pmid37207671, year = {2024}, author = {Turner, S and Naidoo, CA and Usher, TJ and Kruger, A and Venter, C and Laubscher, GJ and Khan, MA and Kell, DB and Pretorius, E}, title = {Increased Levels of Inflammatory and Endothelial Biomarkers in Blood of Long COVID Patients Point to Thrombotic Endothelialitis.}, journal = {Seminars in thrombosis and hemostasis}, volume = {50}, number = {2}, pages = {288-294}, doi = {10.1055/s-0043-1769014}, pmid = {37207671}, issn = {1098-9064}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; alpha-2-Antiplasmin ; *COVID-19 ; *Thrombosis ; von Willebrand Factor/metabolism ; Biomarkers ; }, abstract = {The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID.}, } @article {pmid37205522, year = {2023}, author = {Durstenfeld, MS and Peluso, MJ and Spinelli, MA and Li, D and Hoh, R and Gandhi, M and Henrich, TJ and Aras, MA and Long, CS and Deeks, SG and Hsue, PY}, title = {Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.05.01.23289358}, pmid = {37205522}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Long COVID has been associated with reduced exercise capacity, but whether SARS-CoV-2 infection or Long COVID is associated with reduced exercise capacity among people with HIV (PWH) has not been reported. We hypothesized that PWH with cardiopulmonary post-acute symptoms of COVID-19 (PASC) would have reduced exercise capacity due to chronotropic incompetence.

METHODS: We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH. We evaluated associations of HIV, prior SARS-CoV-2 infection, and cardiopulmonary PASC with exercise capacity (peak oxygen consumption, VO 2) and adjusted heart rate reserve (AHRR, chronotropic measure) with adjustment for age, sex, and body mass index.

RESULTS: We included 83 participants (median age 54, 35% female). All 37 PWH were virally suppressed; 23 (62%) had prior SARS-CoV-2 infection, and 11 (30%) had PASC. Peak VO 2 was reduced among PWH (80% predicted vs 99%; p=0.005), a difference of 5.5 ml/kg/min (95%CI 2.7-8.2, p<0.001). Chronotropic incompetence more prevalent among PWH (38% vs 11%; p=0.002), and AHRR was reduced among PWH (60% vs 83%, p<0.0001). Among PWH, exercise capacity did not vary by SARS-CoV-2 coinfection, but chronotropic incompetence was more common among PWH with PASC: 3/14 (21%) without SARS-CoV-2, 4/12 (25%) with SARS-CoV-2 without PASC, and 7/11 (64%) with PASC (p=0.04 PASC vs no PASC).

CONCLUSIONS: Exercise capacity and chronotropy are lower among PWH compared to SARS-CoV-2 infected individuals without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a mechanism limiting exercise capacity among PWH.}, } @article {pmid37205352, year = {2023}, author = {Stussman, B and Calco, B and Norato, G and Gavin, A and Chigurupati, S and Nath, A and Walitt, B}, title = {A Mixed Methods System for the Assessment of Post Exertional Malaise in Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37205352}, abstract = {BACKGROUND: A central feature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is post exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. PEM is also a feature of Long COVID. Dynamic measures of PEM have historically included scaled questionnaires which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semi-structured qualitative interviews (QIs) at the same intervals as Visual Analog Scale (VAS) measures after a Cardiopulmonary Exercise Test (CPET).

METHODS: Ten ME/CFS and nine healthy volunteers participated in a CPET. For each participant, PEM symptom VAS (7 symptoms) and semi-structured QIs were administered at six timepoints over 72 hours before and after a single CPET. QI data were used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for each patient. QI data were used to determine the symptom trajectory and peak of PEM. Performance of QI and VAS data were compared to each other using Spearman correlations.

RESULTS: QIs documented that each ME/CFS volunteer had a unique PEM experience, with differences noted in the onset, severity, trajectory over time, and most bothersome symptom. No healthy volunteers experienced PEM. Scaled QI data were able to identify PEM peaks and trajectories, even when VAS scales were unable to do so due to known ceiling and floor effects. QI and VAS fatigue data corresponded well prior to exercise (baseline, r=0.7) but poorly at peak PEM (r=0.28) and with the change from baseline to peak (r=0.20). When the most bothersome symptom identified from QIs was used, these correlations improved (r=.0.77, 0.42. and 0.54 respectively) and reduced the observed VAS scale ceiling and floor effects.

CONCLUSION: QIs were able to capture changes in PEM severity and symptom quality over time in all the ME/CFS volunteers, even when VAS scales failed to do so. Information collected from QIs also improved the performance of VAS. Measurement of PEM can be improved by using a quantitative-qualitative mixed model approach.}, } @article {pmid37205321, year = {2023}, author = {Barnhill, JL and Roth, IJ and Miller, VE and Baratta, JM and Chilcoat, A and Kavalakatt, BM and Tiedt, MK and Thompson, KL and Gardiner, P}, title = {Pilot Observational Study of Patient Reported Outcome Measures for Long COVID Patients in Virtual Integrative Medical Group Visits.}, journal = {Global advances in integrative medicine and health}, volume = {12}, number = {}, pages = {27536130231174236}, pmid = {37205321}, issn = {2753-6130}, abstract = {BACKGROUND: Long COVID is a common, debilitating post-infectious illness for which effective management is unknown. Integrative Medical Group Visits (IMGV) are effective interventions for chronic conditions and could benefit Long COVID patients. More information is needed regarding existing patient reported outcome measures (PROMs) to evaluate efficacy of IMGV for Long COVID.

OBJECTIVE: This study assessed the feasibility of specific PROMS to evaluate IMGVs for Long COVID. Findings will inform future efficacy trials.

METHODS: The Perceived Stress Scale (PSS-10), General Anxiety Disorder two-question tool (GAD-2), Fibromyalgia Symptom Severity scale (SSS), and Measure Yourself Medical Outcome Profile (MYMOP®) were collected pre- and post-group by teleconferencing platform or telephone and compared using paired t-tests. Patients were recruited from a Long COVID specialty clinic where they participated in 2-hour - 8 weekly IMGV sessions online.

RESULTS: Twenty-seven participants enrolled and completed pre-group surveys. Fourteen participants were reachable by phone post-group and completed all pre and post PROMs (78.6% female, 71.4% non-Hispanic White, mean age 49). MYMOP® primary symptomatology was fatigue, shortness of breath and "brain fog". Symptoms decreased in interference when compared to pre-group levels (mean difference -1.3 [95% CI-2.2, -.5]). PSS scores decreased (-3.4 [95% CI -5.8, -1.1]), and GAD-2 mean difference was -1.43 (95% CI -3.12, .26). There were no changes in SSS scores of fatigue (-.21 [95% CI -.68,0.25]), waking unrefreshed (.00 [95%CI -.32, -.32]), or trouble thinking (-.21 [95% CI -.78,0.35]).

CONCLUSION: All PROMs were feasible to administer via teleconferencing platform or telephone. The PSS, GAD-2 and MYMOP® are promising PROMs to track Long COVID symptomatology among IMGV participants. The SSS, while feasible to administer, did not change compared to baseline. Larger, controlled studies are needed to determine the efficacy of virtual IMGVs to address the needs of this large and growing population.}, } @article {pmid37204997, year = {2023}, author = {Narasimhan, B and Calambur, A and Moras, E and Wu, L and Aronow, W}, title = {Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.}, journal = {Vascular health and risk management}, volume = {19}, number = {}, pages = {303-316}, pmid = {37204997}, issn = {1178-2048}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; Disease Progression ; }, abstract = {The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.}, } @article {pmid37202336, year = {2023}, author = {Canas, LS and Molteni, E and Deng, J and Sudre, CH and Murray, B and Kerfoot, E and Antonelli, M and Rjoob, K and Capdevila Pujol, J and Polidori, L and May, A and Österdahl, MF and Whiston, R and Cheetham, NJ and Bowyer, V and Spector, TD and Hammers, A and Duncan, EL and Ourselin, S and Steves, CJ and Modat, M}, title = {Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations.}, journal = {The Lancet. Digital health}, volume = {5}, number = {7}, pages = {e421-e434}, pmid = {37202336}, issn = {2589-7500}, support = {/WT_/Wellcome Trust/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Longitudinal Studies ; Artificial Intelligence ; Pandemics ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; }, abstract = {BACKGROUND: Self-reported symptom studies rapidly increased understanding of SARS-CoV-2 during the COVID-19 pandemic and enabled monitoring of long-term effects of COVID-19 outside hospital settings. Post-COVID-19 condition presents as heterogeneous profiles, which need characterisation to enable personalised patient care. We aimed to describe post-COVID-19 condition profiles by viral variant and vaccination status.

METHODS: In this prospective longitudinal cohort study, we analysed data from UK-based adults (aged 18-100 years) who regularly provided health reports via the Covid Symptom Study smartphone app between March 24, 2020, and Dec 8, 2021. We included participants who reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2 who subsequently developed long COVID (ie, symptoms lasting longer than 28 days from the date of the initial positive test). We separately defined post-COVID-19 condition as symptoms that persisted for at least 84 days after the initial positive test. We did unsupervised clustering analysis of time-series data to identify distinct symptom profiles for vaccinated and unvaccinated people with post-COVID-19 condition after infection with the wild-type, alpha (B.1.1.7), or delta (B.1.617.2 and AY.x) variants of SARS-CoV-2. Clusters were then characterised on the basis of symptom prevalence, duration, demography, and previous comorbidities. We also used an additional testing sample with additional data from the Covid Symptom Study Biobank (collected between October, 2020, and April, 2021) to investigate the effects of the identified symptom clusters of post-COVID-19 condition on the lives of affected people.

FINDINGS: We included 9804 people from the COVID Symptom Study with long COVID, 1513 (15%) of whom developed post-COVID-19 condition. Sample sizes were sufficient only for analyses of the unvaccinated wild-type, unvaccinated alpha variant, and vaccinated delta variant groups. We identified distinct profiles of symptoms for post-COVID-19 condition within and across variants: four endotypes were identified for infections due to the wild-type variant (in unvaccinated people), seven for the alpha variant (in unvaccinated people), and five for the delta variant (in vaccinated people). Across all variants, we identified a cardiorespiratory cluster of symptoms, a central neurological cluster, and a multi-organ systemic inflammatory cluster. These three main clusers were confirmed in a testing sample. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant.

INTERPRETATION: Our unsupervised analysis identified different profiles of post-COVID-19 condition, characterised by differing symptom combinations, durations, and functional outcomes. Our classification could be useful for understanding the distinct mechanisms of post-COVID-19 condition, as well as for identification of subgroups of individuals who might be at risk of prolonged debilitation.

FUNDING: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, UK Alzheimer's Society, and ZOE.}, } @article {pmid37201420, year = {2023}, author = {Kahraman, AB and Yıldız, Y and Çıkı, K and Erdal, I and Akar, HT and Dursun, A and Tokatlı, A and Sivri, S}, title = {COVID-19 in inherited metabolic disorders: Clinical features and risk factors for disease severity.}, journal = {Molecular genetics and metabolism}, volume = {139}, number = {2}, pages = {107607}, pmid = {37201420}, issn = {1096-7206}, mesh = {Adult ; Obesity/complications/epidemiology ; SARS-CoV-2 ; Child ; Risk Factors ; *Metabolic Diseases/epidemiology ; *COVID-19/epidemiology/complications ; Humans ; Post-Acute COVID-19 Syndrome ; Patient Acuity ; Systemic Inflammatory Response Syndrome ; }, abstract = {BACKGROUND: Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center.

METHODS: Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD.

RESULTS: Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults.

DISCUSSION: This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.}, } @article {pmid37201006, year = {2023}, author = {Evcik, D}, title = {Musculoskeletal involvement: COVID-19 and post COVID 19.}, journal = {Turkish journal of physical medicine and rehabilitation}, volume = {69}, number = {1}, pages = {1-7}, pmid = {37201006}, issn = {2587-1250}, abstract = {The worldwide pandemic of coronavirus disease 2019 (COVID-19) was known to predominantly affect the lungs, but it was realized that COVID-19 had a large variety of clinical involvement. Cardiovascular, gastrointestinal, neurological, and musculoskeletal systems are involved by direct or indirect mechanisms with various manifestations. The musculoskeletal involvement can manifest during COVID-19 infection, due to medications used for the treatment of COVID-19, and in the post/long COVID-19 syndrome. The major symptoms are fatigue, myalgia/arthralgia, back pain, low back pain, and chest pain. During the last two years, musculoskeletal involvement increased, but no clear consensus was obtained about the pathogenesis. However, there is valuable data that supports the hypothesis of angiotensinconverting enzyme 2, inflammation, hypoxia, and muscle catabolism. Additionally, medications that were used for treatment also have musculoskeletal adverse effects, such as corticosteroid-induced myopathy and osteoporosis. Therefore, while deciding the drugs, priorities and benefits should be taken into consideration. Symptoms that begin three months from the onset of the COVID-19 infection, continue for at least two months, and cannot be explained by another diagnosis is accepted as post/long COVID-19 syndrome. Prior symptoms may persist and fluctuate, or new symptoms may manifest. In addition, there must be at least one symptom of infection. Most common musculoskeletal symptoms are myalgia, arthralgia, fatigue, back pain, muscle weakness, sarcopenia, impaired exercise capacity, and physical performance. In addition, the female sex, obesity, elderly patients, hospitalization, prolonged immobility, having mechanical ventilation, not having vaccination, and comorbid disorders can be accepted as clinical predictors for post/long COVID-19 syndrome. Musculoskeletal pain is also a major problem and tends to be in chronic form. There is no consensus on the mechanism, but inflammation and angiotensin-converting enzyme 2 seem to play an important role. Localized and generalized pain may occur after COVID-19, and general pain is at least as common as localized pain. An accurate diagnosis allows physicians to initiate pain management and proper rehabilitation programs.}, } @article {pmid37199425, year = {2023}, author = {Nishimi, K and Tan, J and Scoglio, A and Choi, KW and Kelley, DP and Neylan, TC and O'Donovan, A}, title = {Psychological Resilience to Trauma and Risk of COVID-19 Infection and Somatic Symptoms Across 2 Years.}, journal = {Psychosomatic medicine}, volume = {85}, number = {6}, pages = {488-497}, pmid = {37199425}, issn = {1534-7796}, support = {IK2 CX002627/CX/CSRD VA/United States ; K01 MH109871/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; *Resilience, Psychological ; Pandemics ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; *Medically Unexplained Symptoms ; }, abstract = {OBJECTIVE: Exposure to trauma increases the risk of somatic symptoms, as well as acute and chronic physical diseases. However, many individuals display psychological resilience, showing positive psychological adaptation despite trauma exposure. Resilience to prior trauma may be a protective factor for physical health during subsequent stressors, including the COVID-19 pandemic.

METHODS: Using data from 528 US adults in a longitudinal cohort study, we examined psychological resilience to lifetime potentially traumatic events early in the pandemic and the risk of COVID-19 infection and somatic symptoms across 2 years of follow-up. Resilience was defined as level of psychological functioning relative to lifetime trauma burden, assessed in August 2020. Outcomes included COVID-19 infection and symptom severity, long COVID, and somatic symptoms assessed every 6 months for 24 months. Using regression models, we examined associations between resilience and each outcome adjusting for covariates.

RESULTS: Higher psychological resilience to trauma was associated with a lower likelihood of COVID-19 infection over time, with one standard deviation higher resilience score associated with a 31% lower likelihood of COVID-19 infection, adjusting for sociodemographics and vaccination status. Furthermore, higher resilience was associated with lower levels of somatic symptoms during the pandemic, adjusting for COVID-19 infection and long COVID status. In contrast, resilience was not associated with COVID-19 disease severity or long COVID.

CONCLUSIONS: Psychological resilience to prior trauma is associated with lower risk of COVID-19 infection and lower somatic symptoms during the pandemic. Promoting psychological resilience to trauma may benefit not only mental but also physical health.}, } @article {pmid37197595, year = {2023}, author = {Krishnadath, I and Harkisoen, S and Gopie, F and van der Hilst, K and Hollum, M and Woittiez, L and Baldew, SS}, title = {Prevalence of persistent symptoms after having COVID-19 in a cohort in Suriname.}, journal = {Revista panamericana de salud publica = Pan American journal of public health}, volume = {47}, number = {}, pages = {e79}, pmid = {37197595}, issn = {1680-5348}, abstract = {OBJECTIVES: To determine the prevalence of persistent symptoms after having coronavirus disease 2019 (COVID-19) in a cohort in Suriname, and assess the factors associated with long COVID.

METHODS: A sample of adults 18 years and older who were registered 3-4 months previously in a national database because of a positive COVID-19 test were selected. They were interviewed about socioeconomic characteristics, pre-COVID-19 health status and lifestyle, and symptoms during and after COVID-19. A subset of participants underwent a physical examination to determine body mass index, waist circumference, cardiovascular parameters, lung function, and functionality.

RESULTS: A total of 106 participants (mean age 49 (standard deviation 15) years; 62.3% female) were interviewed, of whom 32 were physically examined. The greatest proportion of participants was of Hindustani descent (22.6%). Overall, 37.7% of participants were physically inactive, 26.4% had hypertension or diabetes mellitus, and 13.2% had been previously diagnosed with heart disease. Most participants (56.6%) had experienced mild COVID-19 and 14.2% had experienced severe COVID-19. A large proportion (39.6%) had experienced at least one persistent symptom after recovery from acute COVID-19 and more women were affected (47.0% of women versus 27.5% of men). Fatigue and alopecia were the most common symptoms, followed by dyspnea and sleep disturbance. Differences were observed between ethnic groups. Based on physical examination, 45.0% of the subset was obese and 67.7% had very high waist-circumference.

CONCLUSIONS: About 40% of the cohort had at least one persistent symptom 3-4 months after having had COVID-19, with differences observed by sex and ethnic group.}, } @article {pmid37196322, year = {2023}, author = {}, title = {Correction to: The health impact of long COVID during the 2021-2022 Omicron wave in Australia: a quantitative burden of disease study.}, journal = {International journal of epidemiology}, volume = {52}, number = {3}, pages = {967}, doi = {10.1093/ije/dyad069}, pmid = {37196322}, issn = {1464-3685}, } @article {pmid37195978, year = {2023}, author = {Mat Hassan, N and Salim, HS and Amaran, S and Yunus, NI and Yusof, NA and Daud, N and Fry, D}, title = {Prevalence of mental health problems among children with long COVID: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0282538}, pmid = {37195978}, issn = {1932-6203}, mesh = {Adolescent ; Humans ; Child ; *COVID-19/epidemiology ; Mental Health ; Post-Acute COVID-19 Syndrome ; Pandemics ; Prevalence ; Cross-Sectional Studies ; Anxiety/epidemiology/diagnosis ; Depression/epidemiology/diagnosis ; }, abstract = {INTRODUCTION: The number of children with mental health problems has more than doubled since the COVID-19 pandemic. However, the effect of long Covid on children's mental health is still debatable. Recognising long Covid as a risk factor for mental health problems in children will increase awareness and screening for mental health problems following COVID-19 infection, resulting in earlier intervention and lower morbidity. Therefore, this study aimed to determine the proportion of mental health problems post-COVID-19 infection in children and adolescents, and to compare them with the population with no previous COVID-19 infection.

METHODOLOGY: A systematic search was done in seven databases using pre-defined search terms. Cross-sectional, cohort and interventional studies reporting the proportion of mental health problems among children with long COVID in the English language from 2019 to May 2022 were included. Selection of papers, extraction of data and quality assessment were done independently by two reviewers. Studies with satisfactory quality were included in meta-analysis using R and Revman software programmes.

RESULTS: The initial search retrieved 1848 studies. After screening, 13 studies were included in the quality assessments. Meta-analysis showed children who had previous COVID-19 infection had more than two times higher odds of having anxiety or depression, and 14% higher odds of having appetite problems, compared to children with no previous infection. The pooled prevalence of mental health problems among the population were as follows; anxiety: 9%(95% CI:1, 23), depression: 15%(95% CI:0.4, 47), concentration problems: 6%(95% CI: 3, 11), sleep problems: 9%(95% CI:5, 13), mood swings: 13% (95%CI:5, 23) and appetite loss: 5%(95% CI:1, 13). However, studies were heterogenous and lack data from low- and middle-income countries.

CONCLUSION: Anxiety, depression and appetite problems were significantly increased among post-COVID-19 infected children, compared to those without a previous infection, which may be attributed to long COVID. The findings underscore the importance of screening and early intervention of children post-COVID-19 infection at one month and between three to four months.}, } @article {pmid37195688, year = {2023}, author = {Nehme, M and Schneider, F and Perrin, A and Sum Yu, W and Schmitt, S and Violot, G and Ducrot, A and Tissandier, F and Posfay-Barbe, K and Guessous, I}, title = {The Development of a Chatbot Technology to Disseminate Post-COVID-19 Information: Descriptive Implementation Study.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e43113}, pmid = {37195688}, issn = {1438-8871}, mesh = {Adult ; Child ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Ecosystem ; Health Personnel/psychology ; Communication ; }, abstract = {BACKGROUND: Post-COVID-19, or long COVID, has now affected millions of individuals, resulting in fatigue, neurocognitive symptoms, and an impact on daily life. The uncertainty of knowledge around this condition, including its overall prevalence, pathophysiology, and management, along with the growing numbers of affected individuals, has created an essential need for information and disease management. This has become even more critical in a time of abundant online misinformation and potential misleading of patients and health care professionals.

OBJECTIVE: The RAFAEL platform is an ecosystem created to address the information about and management of post-COVID-19, integrating online information, webinars, and chatbot technology to answer a large number of individuals in a time- and resource-limited setting. This paper describes the development and deployment of the RAFAEL platform and chatbot in addressing post-COVID-19 in children and adults.

METHODS: The RAFAEL study took place in Geneva, Switzerland. The RAFAEL platform and chatbot were made available online, and all users were considered participants of this study. The development phase started in December 2020 and included developing the concept, the backend, and the frontend, as well as beta testing. The specific strategy behind the RAFAEL chatbot balanced an accessible interactive approach with medical safety, aiming to relay correct and verified information for the management of post-COVID-19. Development was followed by deployment with the establishment of partnerships and communication strategies in the French-speaking world. The use of the chatbot and the answers provided were continuously monitored by community moderators and health care professionals, creating a safe fallback for users.

RESULTS: To date, the RAFAEL chatbot has had 30,488 interactions, with an 79.6% (6417/8061) matching rate and a 73.2% (n=1795) positive feedback rate out of the 2451 users who provided feedback. Overall, 5807 unique users interacted with the chatbot, with 5.1 interactions per user, on average, and 8061 stories triggered. The use of the RAFAEL chatbot and platform was additionally driven by the monthly thematic webinars as well as communication campaigns, with an average of 250 participants at each webinar. User queries included questions about post-COVID-19 symptoms (n=5612, 69.2%), of which fatigue was the most predominant query (n=1255, 22.4%) in symptoms-related stories. Additional queries included questions about consultations (n=598, 7.4%), treatment (n=527, 6.5%), and general information (n=510, 6.3%).

CONCLUSIONS: The RAFAEL chatbot is, to the best of our knowledge, the first chatbot developed to address post-COVID-19 in children and adults. Its innovation lies in the use of a scalable tool to disseminate verified information in a time- and resource-limited environment. Additionally, the use of machine learning could help professionals gain knowledge about a new condition, while concomitantly addressing patients' concerns. Lessons learned from the RAFAEL chatbot will further encourage a participative approach to learning and could potentially be applied to other chronic conditions.}, } @article {pmid37195116, year = {2023}, author = {Delévaux, I and Duquenne, C and Kokkinakis, I and Favrat, B}, title = {[Neuropsychiatric manifestations of post COVID-19 Syndrome and Disability Insurance (DI)].}, journal = {Revue medicale suisse}, volume = {19}, number = {827}, pages = {992-993}, doi = {10.53738/REVMED.2023.19.827.992}, pmid = {37195116}, issn = {1660-9379}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Insurance, Disability ; }, abstract = {Long COVID, frequently associated to neuropsychiatric manifestations, impacts the ability of patients to return to work and often requires adjustments of the previous workstation. Due to the duration of the symptoms and the professional consequences, disability insurance (DI) procedures may be necessary. Because the persistent symptoms of Long COVID are often subjective and unspecific, the medical report to the DI should include a detailed description of the functional impact of these manifestations.}, } @article {pmid37195114, year = {2023}, author = {Chatton, P and Martins, M and Carlier, S and Bieler-Aeschlimann, M}, title = {[Long COVID : which neuropsychological intervention ? The example applied at the Leenaards Memory Centre].}, journal = {Revue medicale suisse}, volume = {19}, number = {827}, pages = {979-983}, doi = {10.53738/REVMED.2023.19.827.979}, pmid = {37195114}, issn = {1660-9379}, mesh = {Humans ; Quality of Life ; *COVID-19 ; Cognition ; *Sleep Initiation and Maintenance Disorders/etiology/therapy ; Neuropsychological Tests ; Fatigue/psychology ; }, abstract = {A "Long COVID" care management was created at the Leenaards Memory Centre (Lausanne University Hospital) to meet the high demand for neuropsychological examinations in the patients which have persistent symptoms for several months. A multidisciplinary evaluation specifically addressing aspects of fatigue and sleep as well as cognition has been developed to receive these patients. Depending on the severity of their symptoms, they are then oriented towards a holistic group treatment, integrating cognitive remediation including psycho-education, restorative and compensatory methods to cope with their cognitive difficulties, and tools to manage the various symptoms of COVID-long (fatigue, insomnia, stress, depression and reduced quality of life).}, } @article {pmid37195113, year = {2023}, author = {Berney, A and Marillier, G}, title = {[Psychiatric dimensions of post-COVID-19 condition : an overview].}, journal = {Revue medicale suisse}, volume = {19}, number = {827}, pages = {975-978}, doi = {10.53738/REVMED.2023.19.827.975}, pmid = {37195113}, issn = {1660-9379}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Anxiety Disorders ; Fatigue/etiology ; Pandemics ; }, abstract = {In the aftermath of the SARS-CoV-2 pandemic, many patients developed a set of persistent and disabling symptoms, commonly referred to as "long COVID" and defined as "post-COVID-19 condition" by the World Health Organization. The multi-systemic impairments caused by this condition include neuropsychiatric symptoms characterized by the presence of fatigue, cognitive and sleep disturbances, and increased rates of mood and anxiety disorders. Despite their high incidence and a significant risk of chronicity, they remain poorly understood. This article provides an overview of the psychiatric aspects of post-COVID-19 condition and their treatment.}, } @article {pmid37195112, year = {2023}, author = {Nuber-Champier, A and Voruz, P and Cionca, A and Jacot De Alcântara, I and Péron, JA and Assal, F}, title = {[Long COVID : neurological aspects].}, journal = {Revue medicale suisse}, volume = {19}, number = {827}, pages = {972-974}, doi = {10.53738/REVMED.2023.19.827.972}, pmid = {37195112}, issn = {1660-9379}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Interdisciplinary Studies ; Knowledge ; }, abstract = {The study of post-COVID-19 symptomatology revealed a first wave of post-acute (persistence of symptoms less than 3 months) neurocognitive symptoms. However, some of these symptoms worsened, while others improved. To our knowledge, these symptoms may persist for up to 1 to 2 years after infection. The intensity, variability and persistence of neurocognitive symptoms may rise the hypotheses of accelerated neurodegenerative processes, as well as neuropsychiatric and/or genetic vulnerabilities that are still poorly understood. Moreover, the multi-organ manifestations of post-COVID-19 symptoms remind us of the importance of promoting an interdisciplinary perspective at both clinical and fundamental levels. Finally, many social and economic issues parallel to the neuropathological consequences remain to be investigated.}, } @article {pmid37194484, year = {2023}, author = {MCCarthy, MW}, title = {Metformin as a potential treatment for COVID-19.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {10}, pages = {1199-1203}, doi = {10.1080/14656566.2023.2215385}, pmid = {37194484}, issn = {1744-7666}, mesh = {Humans ; Middle Aged ; *COVID-19 ; SARS-CoV-2 ; *Metformin/therapeutic use ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; }, abstract = {INTRODUCTION: Early treatment for SARS-CoV-2 infection is essential to limit the clinical progression of COVID-19. However, limited therapeutic options are available for standard-risk patients, including those under age 50 who have received the primary series of COVID-19 vaccination as well as a bivalent booster.

AREAS COVERED: Metformin is a widely used, inexpensive antihyperglycemic for the treatment of diabetes mellitus type 2 as well as polycystic ovarian syndrome, with a well-described safety profile.

EXPERT OPINION: Although the mechanism of action has not been fully elucidated, metformin is known to alter glucose metabolism and is under investigation as an antiviral agent, demonstrating in vitro and in vivo activity against SARS-CoV-2. Recent work suggests metformin may also serve as a therapeutic option for patients with COVID-19 as well as those with post-acute sequelae of SARS-CoV-2 infection, known more commonly as 'long COVID-19.' This manuscript examines what is known about metformin for the treatment of COVID-19 and explores how this drug may be used in the future to address the SARS-CoV-2 pandemic.}, } @article {pmid37193738, year = {2023}, author = {Samper-Pardo, M and León-Herrera, S and Oliván-Blázquez, B and Méndez-López, F and Domínguez-García, M and Sánchez-Recio, R}, title = {Effectiveness of a telerehabilitation intervention using ReCOVery APP of long COVID patients: a randomized, 3-month follow-up clinical trial.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {7943}, pmid = {37193738}, issn = {2045-2322}, mesh = {Humans ; *Telerehabilitation/methods ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Follow-Up Studies ; *Mobile Applications ; }, abstract = {The main objective of this study is to analyze the clinical efficacy of telerehabilitation in the recovery of Long COVID patients through ReCOVery APP for 3 months, administered in the Primary Health Care context. The second objective is to identify significant models associated with an improvement in the study variables. An open-label randomized clinical trial was conducted using two parallel groups of a total of 100 Long COVID patients. The first group follows the treatment as usual methods established by their general practitioner (control group) and the second follows the same methods and also uses ReCOVery APP (intervention group). After the intervention, no significant differences were found in favour of the group intervention. Regarding adherence, 25% of the participants made significant use of the APP. Linear regression model establishes that the time of use of ReCOVery APP predicts an improvement in physical function (b = 0.001; p = 0.005) and community social support (b = 0.004; p = 0.021). In addition, an increase in self-efficacy and health literacy also contribute to improving cognitive function (b = 0.346; p = 0.001) and reducing the number of symptoms (b = 0.226; p = 0.002), respectively. In conclusion, the significant use of ReCOVery APP can contribute to the recovery of Long COVID patients. Trial Registration No.: ISRCTN91104012.}, } @article {pmid37192812, year = {2023}, author = {Bundy, N and De Jesus, M and Lytle, M and Calabrese, L and Gobin, C and Dyhrberg, M}, title = {Self-evidence-based digital care programme improves health-related quality of life in adults with a variety of autoimmune diseases and long COVID: a retrospective study.}, journal = {RMD open}, volume = {9}, number = {2}, pages = {}, pmid = {37192812}, issn = {2056-5933}, mesh = {Humans ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Quality of Life ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; *Arthritis, Rheumatoid/epidemiology/therapy ; }, abstract = {OBJECTIVE: To retrospectively investigate the feasibility and impact on health-related quality of life (HRQoL) of a digital care programme (DCP) designed to guide personalised diet and integrative interventions in a variety of autoimmune diseases and long COVID.

METHODS: Adults who participated in the DCP between April 2020 and June 2022, and for whom baseline (BL) and end-of-programme (EOP) Patient-Reported Outcomes Measurement Information System (PROMIS) scores were available, were included in this retrospective study. Changes from BL to EOP were calculated using standardised T-scores.

RESULTS: Two hundred two adults between 17 and 82 years old were included. Diagnoses included: rheumatoid arthritis (20.1%); long COVID (14.9%); psoriatic arthritis (10.9%); psoriasis (8.9%); systemic lupus erythematosus (6.4%); inflammatory bowel disease (5.9%); multiple sclerosis (5.9%); ankylosing spondylitis (5.4%) and other (23.3%). On average, individuals entered observations 7.6 times/day on 86% of programme days, attended 14 coach sessions and completed the programme in an average of 17.2 weeks. Statistically significant improvements were seen in all 10 PROMIS domains analysed. Individuals with higher severity of compromise at BL experienced greater average improvements than all-comers in all 10 PROMIS domains included.

CONCLUSION: An evidence-based DCP that uses patient data to help identify hidden symptom triggers and guide personalised dietary and other non-pharmacological interventions was associated with a high level of engagement and adherence and statistically significant, clinically meaningful improvements in HRQoL. Those with the least favourable PROMIS scores at BL experienced the greatest improvements.}, } @article {pmid37192595, year = {2023}, author = {Scholkmann, F and May, CA}, title = {COVID-19, post-acute COVID-19 syndrome (PACS, "long COVID") and post-COVID-19 vaccination syndrome (PCVS, "post-COVIDvac-syndrome"): Similarities and differences.}, journal = {Pathology, research and practice}, volume = {246}, number = {}, pages = {154497}, pmid = {37192595}, issn = {1618-0631}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; SARS-CoV-2 ; Vaccination ; }, abstract = {Worldwide there have been over 760 million confirmed coronavirus disease 2019 (COVID-19) cases, and over 13 billion COVID-19 vaccine doses have been administered as of April 2023, according to the World Health Organization. An infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to an acute disease, i.e. COVID-19, but also to a post-acute COVID-19 syndrome (PACS, "long COVID"). Currently, the side effects of COVID-19 vaccines are increasingly being noted and studied. Here, we summarise the currently available indications and discuss our conclusions that (i) these side effects have specific similarities and differences to acute COVID-19 and PACS, that (ii) a new term should be used to refer to these side effects (post-COVID-19 vaccination syndrome, PCVS, colloquially "post-COVIDvac-syndrome"), and that (iii) there is a need to distinguish between acute COVID-19 vaccination syndrome (ACVS) and post-acute COVID-19 vaccination syndrome (PACVS) - in analogy to acute COVID-19 and PACS ("long COVID"). Moreover, we address mixed forms of disease caused by natural SARS-CoV-2 infection and COVID-19 vaccination. We explain why it is important for medical diagnosis, care and research to use the new terms (PCVS, ACVS and PACVS) in order to avoid confusion and misinterpretation of the underlying causes of disease and to enable optimal medical therapy. We do not recommend to use the term "Post-Vac-Syndrome" as it is imprecise. The article also serves to address the current problem of "medical gaslighting" in relation to PACS and PCVS by raising awareness among the medical professionals and supplying appropriate terminology for disease.}, } @article {pmid37192536, year = {2023}, author = {Alhotye, M and Daynes, E and Gerlis, C and Singh, SJ}, title = {Symptoms burden and rehabilitation preference after an episode of COVID-19: A patients survey.}, journal = {Chronic respiratory disease}, volume = {20}, number = {}, pages = {14799731231177316}, pmid = {37192536}, issn = {1479-9731}, mesh = {Humans ; Male ; Middle Aged ; Female ; *COVID-19/epidemiology ; Hospitals ; }, abstract = {BACKGROUND: After COVID-19 infection, individuals can experience a variety of symptoms that might require further treatment. Early data showed the value of adapted pulmonary rehabilitation programmes and technology-based interventions. To develop appropriate services, it is important to understand the symptom burden and the preferred mode of rehabilitation delivery.

METHODS: Post-hospital discharge (H) and post-community-managed (C) individuals received a follow-up call. A survey was completed to assess the most burdensome symptoms for which the patients would require support and their preference for the mode of rehabilitation delivery.

RESULTS: Overall, 160 individuals who received a follow-up call completed the survey (51.2% male, mean [SD] age 54 [15] years) and 126 (78.8%) were post-hospital, while 34 (21.3%) had community-managed infections. A total of 101 (63.1%) reported that COVID-19-related symptoms were affecting their daily activities, and 106 (66.3%) reported their desire to be more active. The most common symptoms identified as needing support were fatigue and shortness of breath. Both groups expressed a preference for a face-to-face group programme (C: 54.8%; H: 46.8%), while (38.7%) of post-community-managed individuals and (40.3%) post-hospital patients preferred a supported digital rehabilitation programme. Few opted a non-digital home-based programme (C: 3.2%; H:12.9%, respectively).

CONCLUSION: The survey responses indicated a significant symptom burden that may benefit from an intervention such as rehabilitation. Preferences for rehabilitation indicated that a face-to-face intervention was preferred by the majority, with a large proportion preferring digital intervention.}, } @article {pmid37192203, year = {2023}, author = {Samper-Pardo, M and León-Herrera, S and Oliván-Blázquez, B and Gascón-Santos, S and Sánchez-Recio, R}, title = {Clinical characterization and factors associated with quality of life in Long COVID patients: Secondary data analysis from a randomized clinical trial.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0278728}, pmid = {37192203}, issn = {1932-6203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Secondary Data Analysis ; *COVID-19 ; Quality of Life/psychology ; Mental Health ; }, abstract = {BACKGROUND: Long COVID patients suffer a negative impact on their quality of life, as well as their functioning, productivity or socialization. There is a need to better understand the individual experience and circumstances surrounding these patients.

OBJECTIVE: To characterize clinical picture of Long COVID patients and to identify factors associated with quality of life.

METHODS: A secondary data analysis from a randomized clinical trial (RCT) was carried out with 100 Long COVID patients treated by Primary Health Care and residents in the territory of Aragon (northeast of Spain). The main variable of the study was quality of life, evaluated using the SF-36 Questionnaire, in relation to socio-demographic and clinical variables. In addition, ten validated scales were used that contemplated their cognitive, affective, functional and social status, as well as personal constructs. Correlation statistics and linear regression model were calculated.

RESULTS: Long COVID patients suffer a decrease in their levels of physical and mental health. On the one hand, the higher number of persistent symptoms (b = -0.900, p = 0.008), worse physical functioning (b = 1.587, p = 0.002) and sleep quality (b = -0.538, p = 0.035) are predictors of worse quality of life, physical subscale. On the other hand, higher educational level (b = 13.167, p = 0.017), lower number of persistent symptoms (b = -0.621, p = 0.057) and higher affective affectation (b = -1.402, p<0.001) are predictors of worse quality of life, mental subscale.

CONCLUSION: It is necessary to design rehabilitation programs that consider both the physical and mental health of these patients, thus obtaining an improvement in their quality of life.}, } @article {pmid37190817, year = {2024}, author = {Spartalis, M and Zweiker, D and Spartalis, E and Iliopoulos, DC and Siasos, G}, title = {Long COVID-19 Syndrome and Sudden Cardiac Death: The Phantom Menace.}, journal = {Current medicinal chemistry}, volume = {31}, number = {1}, pages = {2-6}, doi = {10.2174/0929867330666230515145041}, pmid = {37190817}, issn = {1875-533X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Death, Sudden, Cardiac/etiology ; Anti-Arrhythmia Agents/therapeutic use ; }, } @article {pmid37189823, year = {2023}, author = {Vilaplana-Carnerero, C and Giner-Soriano, M and Dominguez, À and Morros, R and Pericas, C and Álamo-Junquera, D and Toledo, D and Gallego, C and Redondo, A and Grau, M}, title = {Atherosclerosis, Cardiovascular Disease, and COVID-19: A Narrative Review.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189823}, issn = {2227-9059}, abstract = {Atherosclerosis is a chronic inflammatory and degenerative process that mainly occurs in large- and medium-sized arteries and is morphologically characterized by asymmetric focal thickenings of the innermost layer of the artery, the intima. This process is the basis of cardiovascular diseases (CVDs), the most common cause of death worldwide. Some studies suggest a bidirectional link between atherosclerosis and the consequent CVD with COVID-19. The aims of this narrative review are (1) to provide an overview of the most recent studies that point out a bidirectional relation between COVID-19 and atherosclerosis and (2) to summarize the impact of cardiovascular drugs on COVID-19 outcomes. A growing body of evidence shows that COVID-19 prognosis in individuals with CVD is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with CVD after COVID-19. The most common treatments for CVD may influence COVID-19 outcomes. Thus, their implication in the infection process is briefly discussed in this review. A better understanding of the link among atherosclerosis, CVD, and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.}, } @article {pmid37189141, year = {2023}, author = {Chelly, S and Rouis, S and Ezzi, O and Ammar, A and Fitouri, S and Soua, A and Fathallah, I and Njah, M and Mahjoub, M}, title = {Symptoms and risk factors for long COVID in Tunisian population.}, journal = {BMC health services research}, volume = {23}, number = {1}, pages = {487}, pmid = {37189141}, issn = {1472-6963}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Pandemics ; Risk Factors ; }, abstract = {BACKGROUND: The COVID-19 pandemic has presented various challenges, one of which is the discovery that after the acute episode, around 30% of patients experience persistent symptoms or develop new ones, now known as long COVID. This new disease has significant social and financial impacts. The objective is to determine the prevalence of long COVID in the Tunisian population and identify its predictive factors.

METHODS: This was a cross-sectional study conducted among Tunisians who were infected with COVID-19 between March 2020 and February 2022. An online self-administered questionnaire was distributed through social media, radio, and television channels over the course of one month (February 2022). Long COVID was defined as the persistence of existing symptoms or the development of new symptoms within three months after onset, lasting for at least two months, and with no differential diagnosis. We performed univariate and multivariate analyses using binary stepwise logistic regression with a significance level set at 5%.

RESULTS: A total of 1911 patients participated in our study, and the prevalence of long COVID was 46.5%. The two most frequent categories were general and neurological post-COVID syndrome, with a prevalence of 36.7% each. The most commonly observed symptoms were fatigue (63.7%) and memory problems (49.1%). In the multivariate analysis, the predictive factors for long COVID were female gender and age of 60 years or older, while complete anti-COVID vaccination was found to be a protective factor.

CONCLUSIONS: Our study found that complete vaccination was a protective factor against long COVID, while female gender and age of 60 years or older were identified as the main risk factors. These findings are consistent with studies conducted on other ethnic groups. However, many aspects of long COVID remain unclear, including its underlying mechanisms, the identification of which could guide the development of potential effective treatments.}, } @article {pmid37187756, year = {2023}, author = {Antar, AAR and Yu, T and Demko, ZO and Hu, C and Tornheim, JA and Blair, PW and Thomas, DL and Manabe, YC}, title = {Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1147549}, pmid = {37187756}, issn = {1664-3224}, support = {K23 AI135102/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; RNA, Viral/genetics ; COVID-19 Testing ; Myalgia ; Respiratory System ; Brain ; }, abstract = {INTRODUCTION: The incidence of long COVID is substantial, even in people with mild to moderate acute COVID-19. The role of early viral kinetics in the subsequent development of long COVID is largely unknown, especially in individuals who were not hospitalized for acute COVID-19.

METHODS: Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional SARS-CoV-2 test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset.

RESULTS: Self-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct.

DISCUSSION: This work indicates that at least two long COVID symptoms - brain fog and muscle pain - at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.}, } @article {pmid37187732, year = {2023}, author = {Dean, LS and Devendra, G and Jiyarom, B and Subia, N and Tallquist, MD and Nerurkar, VR and Chang, SP and Chow, DC and Shikuma, CM and Park, J}, title = {Corrigendum: Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequelae of SARS-CoV-2 infection.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1209624}, doi = {10.3389/fimmu.2023.1209624}, pmid = {37187732}, issn = {1664-3224}, abstract = {[This corrects the article DOI: 10.3389/fimmu.2022.1076724.].}, } @article {pmid37185834, year = {2023}, author = {Chuang, MH and Wu, JY and Liu, TH and Hsu, WH and Tsai, YW and Huang, PY and Lai, CC}, title = {Efficacy of nirmatrelvir and ritonavir for post-acute COVID-19 sequelae beyond 3 months of SARS-CoV-2 infection.}, journal = {Journal of medical virology}, volume = {95}, number = {4}, pages = {e28750}, doi = {10.1002/jmv.28750}, pmid = {37185834}, issn = {1096-9071}, mesh = {Adult ; Humans ; *Ritonavir/therapeutic use ; *COVID-19 ; COVID-19 Drug Treatment ; Retrospective Studies ; SARS-CoV-2 ; Disease Progression ; }, abstract = {The effect of nirmatrelvir plus ritonavir (NMV-r) on post-acute COVID-19 sequelae beyond 3 months of SARS-CoV-2 infection remains unknown. This retrospective cohort study utilized data from the TriNetX Research Network. We identified nonhospitalized adult patients with COVID-19 receiving a diagnosis between January 1 and July 31, 2022. Propensity score matching (PSM) was used to create two matched cohorts: NMV-r and non-NMV-r groups, respectively. We measured the primary outcomes using a composite of all-cause emergency room (ER) visits or hospitalization and a composite of post-COVID-19 symptoms according to the WHO Delphi consensus, which also stated that post COVID-19 condition occurs usually 3 months from the onset of COVID-19, during the follow-up period between 90 days after the index diagnosis of COVID-19 and the end of follow-up (180 days). Initially, we identified 12 247 patients that received NMV-r within 5 days of diagnosis and 465 135 that did not. After PSM, 12 245 patients remained in each group. During the follow-up period, patients treated with NMV-r had a lower risk of all-cause hospitalization and ER visits compared with untreated patients (659 vs. 955; odds ratio [OR], 0.672; 95% confidence interval [CI], 0.607-0.745; p < 0.0001). However, the overall risk of post-acute COVID-19 symptoms did not significantly differ between the two groups (2265 vs. 2187; OR, 1.043; 95% CI, 0.978-1.114; p = 0.2021). The reduced risk of all-cause ER visits or hospitalization in the NMV-r group and the similarities in the risk of post-acute COVID-19 symptoms between the two groups were consistent in the subgroups stratified by sex, age, and vaccination status. Early NMV-r treatment of nonhospitalized patients with COVID-19 was associated with reduced risk of hospitalization and ER visits during the period of 90-180 days after diagnosis compared with no NMV-r treatment; however, post-acute COVID-19 symptoms and mortality risk did not differ significantly between the groups.}, } @article {pmid37185640, year = {2023}, author = {Thomas, C and Faghy, MA and Owen, R and Yates, J and Ferraro, F and Bewick, T and Haggan, K and Ashton, REM}, title = {Lived experience of patients with Long COVID: a qualitative study in the UK.}, journal = {BMJ open}, volume = {13}, number = {4}, pages = {e068481}, pmid = {37185640}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Female ; Humans ; Middle Aged ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; Quality of Life ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Long COVID is a rapidly evolving global health crisis requiring interdisciplinary support strategies that incorporate the lived experience of patients. Currently, there is a paucity of research documenting the day-to-day experiences of patients living with Long COVID.

OBJECTIVE: To explore the lived experience of Long COVID patients.

STUDY DESIGN: Longitudinal, observation study.

SETTING: An inductive, data-driven, qualitative approach was used to evaluate hand-written diaries obtained from individuals who had been referred to a Derbyshire Long COVID clinic.

PARTICIPANTS: 12 participants (11 females, age 49±10 years, 11 Caucasians) were recruited. Participants were included if they had a previous confirmed or suspected COVID-19 infection with ongoing recovery, >18 years old, understood the study requirements and provided informed consent.

METHOD: Participants were directed to complete self-report diaries over 16 weeks. Responses were transcribed verbatim and analysed using thematic analysis.

RESULTS: Three key themes were highlighted: (1) understanding who helps patients manage symptoms, (2) daily activities and the impact on quality of life and health status and (3) the effect of turbulent and episodic symptom profiles on personal identity and recovery.

CONCLUSIONS: The novel challenges presented by Long COVID are complex with varying inter-related factors that are broadly impacting functional status and quality of life. Support mechanisms must incorporate the lived experiences and foster true collaborations between health professionals, patients and researchers to improve patient outcomes.

TRIAL REGISTRATION NUMBER: NCT04649957.}, } @article {pmid37185117, year = {2023}, author = {Burnett, DM and Skinner, CE}, title = {Year in Review: Long COVID and Pulmonary Rehabilitation.}, journal = {Respiratory care}, volume = {68}, number = {6}, pages = {846-851}, pmid = {37185117}, issn = {1943-3654}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Exercise ; Dyspnea ; Fatigue/etiology ; Quality of Life ; }, abstract = {There have been an estimated 100 million people diagnosed with COVID-19 in the United States, with a majority of patients reporting persistent symptoms expressed as long COVID. The 2 most frequently reported long COVID symptoms are shortness of breath and fatigue. Exercise training during pulmonary rehabilitation (PR) is a successful strategy for improving the lives of people with persistent respiratory symptoms caused by a variety of lung diseases. This narrative review assessed the impact of exercise interventions on functional exercise capacity measures and related symptoms (dyspnea, fatigue) in people with long COVID over the last year. Articles were accessed through electronic databases including PubMed, Embase, CINAHL Plus with full text (EBSCO), and LitCovid. Findings for this Year in Review revealed that exercise interventions and PR show promise for improving functional exercise capacity, dyspnea, and fatigue in people with long COVID. This review supports the need for more rigorous scientific studies on the benefits of structured PR in people with long COVID who have respiratory-related symptoms.}, } @article {pmid37184668, year = {2023}, author = {Szabo, S}, title = {The post-COVID stress syndrome: from the three-stage stress response of Hans Selye to COVID-19.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {2799-2806}, pmid = {37184668}, issn = {1568-5608}, mesh = {Male ; Humans ; Rats ; Animals ; *COVID-19 ; Hydrocortisone ; Stress, Physiological ; SARS-CoV-2 ; Adrenal Cortex Hormones ; Glucocorticoids ; }, abstract = {Stress is the nonspecific response of the body to any demand made upon it, as defined by Hans Selye more than 80 years ago, based on his animal experiments at McGill University in Montreal, Canada. By emphasizing 'nonspecificity' he tried to underline that stress response is elicited my several factors, like nowadays in COVID-19, e.g., fear of infection, social isolation, death in family, loss of employment, etc. Thus, COVID-19 has been the largest new human stressor in the twenty-first century. Selye's studies in rats also revealed 3 stages of stress response: the short initial "alarm reaction" is followed by a longer "stage of resistance", associated with increased levels of corticosterone that is often terminated by a "stage of exhaustion", referring to an exhausted adrenal cortex when the secretion of glucocorticoids drops. Fast forward, that is exactly what has been documented in severe cases of infections caused by the SARS-CoV-2 virus: in hospitalized COVID-19 patients initially the blood levels of cortisol not only have been elevated, but only those with high concentration of this natural anti-inflammatory corticosteroid survived vs. those who had low levels of cortisol, suggesting diminished adrenocortical functions. Furthermore, patients with very severe cases of COVID-19 who ended up in intensive care units had significantly low cortisol blood levels, compared to patients with equal severity of diseases due to other causes. Thus, these 'natural phenomena' in clinical medicine, unfortunately confirmed Selye's studies in experimental animals several decades ago. Still, the good news is that astute clinicians empirically recognized this and started to give potent synthetic glucocorticoids such as dexamethasone to severe COVD-19 patients and this beneficial effect of exogenous corticoids has been extensively confirmed in the scientific literature.}, } @article {pmid37182548, year = {2023}, author = {Servier, C and Porcher, R and Pane, I and Ravaud, P and Tran, VT}, title = {Trajectories of the evolution of post-COVID-19 condition, up to two years after symptoms onset.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {133}, number = {}, pages = {67-74}, pmid = {37182548}, issn = {1878-3511}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: We aimed to identify trajectories of the evolution of post-COVID-19 condition, up to 2 years after symptom onset.

METHODS: The ComPaRe long COVID e-cohort is a prospective cohort of patients with symptoms lasting at least 2 months after SARS-CoV2 infection. We used trajectory modeling to identify different trajectories in the evolution of post-COVID-19 condition, based on symptoms collected every 60 days using the long COVID Symptom Tool.

RESULTS: A total of 2197 patients were enrolled in the cohort between December 2020 and July 2022 when the Omicron variant was not dominant. Three trajectories of the evolution of post-COVID-19 condition were identified: "high persistent symptoms" (4%), "rapidly decreasing symptoms" (5%), and "slowly decreasing symptoms" (91%). Participants with highly persistent symptoms were older and more likely to report a history of systemic diseases. They often reported tachycardia, bradycardia, palpitations, and arrhythmia. Participants with rapidly decreasing symptoms were younger and more likely to report a confirmed infection. They often reported diarrhea and back pain. Participants with slowly decreasing symptoms were more likely to have a history of functional diseases.

CONCLUSION: Most patients with post-COVID-19 condition improve slowly over time, while 5% have rapid improvement in the 2 years after symptom onset and 4% have a persistent condition.}, } @article {pmid37182545, year = {2023}, author = {Srikanth, S and Boulos, JR and Dover, T and Boccuto, L and Dean, D}, title = {Identification and diagnosis of long COVID-19: A scoping review.}, journal = {Progress in biophysics and molecular biology}, volume = {182}, number = {}, pages = {1-7}, pmid = {37182545}, issn = {1873-1732}, support = {P20 GM121342/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Testing ; }, abstract = {Long COVID-19 (LC-19) is a condition that has affected a high percentage of the population that recovered from the initial disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC-19 diagnosis is currently poorly defined because of its variable, multisystem, episodic symptoms, and lack of uniformity in the critical time points associated with the disease. Considering the number of cases, workers' compromised efficiency or inability to return to their duties can affect organizations and impact economies. LC-19 represents a significant burden on multiple levels and effectively reduces quality of life. These factors necessitate the establishment of firm parameters of diagnoses to provide a foundation for ongoing and future studies of clinical characteristics, epidemiology, risk factors, and therapy. In this scoping review, we conducted a literature search across multiple publication sites to identify papers of interest regarding the diagnosis of LC-19. We identified 225 records of interest and categorized them into seven categories. Based on our findings, there are only 11 original papers that outline the diagnostic process in detail with little overlap. This scoping review highlights the lack of consensus regarding the definition and, thereby, the LC-19 diagnosis processes. Due to no clear directive and considering the many unknowns surrounding the natural history of the disease and further recovery/sequelae from COVID-19, continued discussion and agreement on a definition/diagnosis will help future research and management of these patients.}, } @article {pmid37180854, year = {2023}, author = {Izadi, N and Najafi, A and Sadeghniiat-Haghighi, K and Mohammadi, H}, title = {Characterization of Long COVID and Its Contributing Factors among a Population of Health Care Workers in a 6-Month Follow-up.}, journal = {Medical journal of the Islamic Republic of Iran}, volume = {37}, number = {}, pages = {29}, pmid = {37180854}, issn = {1016-1430}, abstract = {BACKGROUND: Health care workers (HCWs) are at the frontline of the fight against the coronavirus disease 2019 (COVID-19). Long COVID is defined as "the persistence of some symptoms of COVID-19, more than 4 weeks after the initial infection." The aim of the present study was to investigate the prevalence of long COVID status among HCWs in the largest hospital complex of Iran.

METHODS: In this cross-sectional study, all patients with COVID-19 who had taken sick leave were included in the study (n = 445). Data regarding sick leave characteristics were collected from the records of the nursing management department of the hospital. Study variables included demographic and occupational information, variables related to mental health assessment, organ systems involved in COVID-19, and duration of symptoms. Frequencies, percentage distributions, means, standard deviation, and range (minimum, maximum) were used as descriptive analysis methods. Associations between symptoms' persistency and clinical characteristics were assessed by logistic and linear regressions.

RESULTS: Age, N95 mask use, and respiratory protection significantly contributed to the persistence of COVID-19 symptoms (P < 0.05). The prevalence of long COVID among HCWs was 9.44% among 445 participants. The loss of taste persisted longer than the other symptoms before returning to normal. Among the postrecovery complications asked, anxiety was the most common persistent mental symptom (58.5%), followed by gloomy mood (46.3%) and low interest (46.2%), respectively.

CONCLUSION: HCWs with COVID-19 symptoms had prolonged symptoms of COVID-19 that can affect their work performance, thus, we recommend evaluating COVID-19 symptoms in HCWs with infection history.}, } @article {pmid37180769, year = {2023}, author = {Condurache, DG and Shanmuganathan, M and Raisi-Estabragh, Z and Raman, B}, title = {Editorial: Post-COVID-19 cardiovascular sequelae.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1191953}, pmid = {37180769}, issn = {2297-055X}, } @article {pmid37179568, year = {2023}, author = {Kenny, G and Townsend, L and Savinelli, S and Mallon, PWG}, title = {Long COVID: Clinical characteristics, proposed pathogenesis and potential therapeutic targets.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1157651}, pmid = {37179568}, issn = {2296-889X}, abstract = {The emergence of persistent ill-health in the aftermath of SARS-CoV-2 infection has presented significant challenges to patients, healthcare workers and researchers. Termed long COVID, or post-acute sequelae of COVID-19 (PASC), the symptoms of this condition are highly variable and span multiple body systems. The underlying pathophysiology remains poorly understood, with no therapeutic agents proven to be effective. This narrative review describes predominant clinical features and phenotypes of long COVID alongside the data supporting potential pathogenesis of these phenotypes including ongoing immune dysregulation, viral persistence, endotheliopathy, gastrointestinal microbiome disturbance, autoimmunity, and dysautonomia. Finally, we describe current potential therapies under investigation, as well as future potential therapeutic options based on the proposed pathogenesis research.}, } @article {pmid37178769, year = {2023}, author = {Nicolai, L and Kaiser, R and Stark, K}, title = {Thromboinflammation in long COVID-the elusive key to postinfection sequelae?.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {8}, pages = {2020-2031}, pmid = {37178769}, issn = {1538-7836}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis ; Inflammation ; Post-Acute COVID-19 Syndrome ; Thromboinflammation ; Disease Progression ; }, abstract = {Long COVID is a public health emergency affecting millions of people worldwide, characterized by heterogeneous symptoms across multiple organ systems. Here, we discuss the current evidence linking thromboinflammation to postacute sequelae of COVID-19. Studies have found persistence of vascular damage with increased circulating markers of endothelial dysfunction, coagulation abnormalities with heightened thrombin generation capacity, and abnormalities in platelet counts in postacute sequelae of COVID-19. Neutrophil phenotype resembles acute COVID-19 with an increase in activation and Neutrophil Extracellular Trap formation. These insights are potentially linked by elevated platelet-neutrophil aggregate formation. This hypercoagulable state in turn can lead to microvascular thrombosis, evidenced by microclots and elevated D-dimer in the circulation as well as perfusion abnormalities in the lungs and brains of patients with long COVID. Also, COVID-19 survivors experience an increased rate of arterial and venous thrombotic events. We discuss 3 important, potentially intertwined hypotheses that might contribute to thromboinflammation in long COVID: lasting structural changes, most prominently endothelial damage, caused during initial infection; a persistent viral reservoir; and immunopathology driven by a misguided immune system. Finally, we outline the necessity for large, well-characterized clinical cohorts and mechanistic studies to clarify the contribution of thromboinflammation to long COVID.}, } @article {pmid37178694, year = {2023}, author = {Yang, C and Zhao, H and Espín, E and Tebbutt, SJ}, title = {Association of SARS-CoV-2 infection and persistence with long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {6}, pages = {504-506}, pmid = {37178694}, issn = {2213-2619}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; }, } @article {pmid37176782, year = {2023}, author = {Buonsenso, D and Morello, R and Mariani, F and De Rose, C and Cortese, R and Vetrugno, L and Valentini, P}, title = {Role of Lung Ultrasound in the Follow-Up of Children with Previous SARS-CoV-2 Infection: A Case-Control Assessment of Children with Long COVID or Fully Recovered.}, journal = {Journal of clinical medicine}, volume = {12}, number = {9}, pages = {}, pmid = {37176782}, issn = {2077-0383}, abstract = {Lung ultrasound (LUS) can detect lower respiratory tract involvement in children with acute SARS-CoV-2 infection. However, its role in follow-up assessments is still unclear. To describe LUS findings in children after SARS-CoV-2 infection, we conducted a prospective study in a population of pediatric patients referred to the post-COVID unit in a tertiary center during the study period from February 2021 to May 2022. Children were classified as recovered from acute infection or with persisting symptoms. LUS was performed in all children and a LUS score (ranging from 0 to 36 points) was calculated according to the Italian Academy of Thoracic Ultrasound. Six hundred forty-seven children (304 females, 47%) were enrolled. The median follow-up evaluation was two months. The median age was 7.9 (IQR: 6) years. At the follow-up evaluation, 251 patients (38.8%) had persistent symptoms, of whom 104 (16.1%) had at least one respiratory symptom. The median LUS level was 2 (IQR: 4). LUS findings and LUS scores did not differ in children with Long COVID compared to the group of children fully recovered from the initial infection. In conclusion, after SARS-CoV-2 infection, LUS was mostly normal or showed minimal artifacts in all groups of children.}, } @article {pmid37176630, year = {2023}, author = {Granholm, AC}, title = {Long-Term Effects of SARS-CoV-2 in the Brain: Clinical Consequences and Molecular Mechanisms.}, journal = {Journal of clinical medicine}, volume = {12}, number = {9}, pages = {}, pmid = {37176630}, issn = {2077-0383}, support = {R01 AG071228/AG/NIA NIH HHS/United States ; RF1 AG061566/AG/NIA NIH HHS/United States ; RF1 AG070153/AG/NIA NIH HHS/United States ; P01 AG014449/AG/NIA NIH HHS/United States ; R01AG061566/GF/NIH HHS/United States ; }, abstract = {Numerous investigations have demonstrated significant and long-lasting neurological manifestations of COVID-19. It has been suggested that as many as four out of five patients who sustained COVID-19 will show one or several neurological symptoms that can last months after the infection has run its course. Neurological symptoms are most common in people who are less than 60 years of age, while encephalopathy is more common in those over 60. Biological mechanisms for these neurological symptoms need to be investigated and may include both direct and indirect effects of the virus on the brain and spinal cord. Individuals with Alzheimer's disease (AD) and related dementia, as well as persons with Down syndrome (DS), are especially vulnerable to COVID-19, but the biological reasons for this are not clear. Investigating the neurological consequences of COVID-19 is an urgent emerging medical need, since close to 700 million people worldwide have now had COVID-19 at least once. It is likely that there will be a new burden on healthcare and the economy dealing with the long-term neurological consequences of severe SARS-CoV-2 infections and long COVID, even in younger generations. Interestingly, neurological symptoms after an acute infection are strikingly similar to the symptoms observed after a mild traumatic brain injury (mTBI) or concussion, including dizziness, balance issues, anosmia, and headaches. The possible convergence of biological pathways involved in both will be discussed. The current review is focused on the most commonly described neurological symptoms, as well as the possible molecular mechanisms involved.}, } @article {pmid37175995, year = {2023}, author = {Gonzalez-Garcia, P and Fiorillo Moreno, O and Zarate Peñata, E and Calderon-Villalba, A and Pacheco Lugo, L and Acosta Hoyos, A and Villarreal Camacho, JL and Navarro Quiroz, R and Pacheco Londoño, L and Aroca Martinez, G and Moares, N and Gabucio, A and Fernandez-Ponce, C and Garcia-Cozar, F and Navarro Quiroz, E}, title = {From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175995}, issn = {1422-0067}, support = {2021//Fundación Carolina/ ; 2021//Universidad Simón Bolívar/ ; PI-0030-2017//Regional Government of Andalusia/ ; 125380763038, 125380763188 and SGR code BPIN 2020000100144.//Colciencias/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; Host Microbial Interactions ; }, abstract = {Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.}, } @article {pmid37175942, year = {2023}, author = {Vassiliou, AG and Vrettou, CS and Keskinidou, C and Dimopoulou, I and Kotanidou, A and Orfanos, SE}, title = {Endotheliopathy in Acute COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175942}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Vascular Diseases/pathology ; Lung/pathology ; Biomarkers ; }, abstract = {The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.}, } @article {pmid37175745, year = {2023}, author = {Chen, TH and Chang, CJ and Hung, PH}, title = {Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175745}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Inflammation ; *Mitochondrial Diseases ; }, abstract = {Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.}, } @article {pmid37175509, year = {2023}, author = {Costanzo, M and De Giglio, MAR and Roviello, GN}, title = {Deciphering the Relationship between SARS-CoV-2 and Cancer.}, journal = {International journal of molecular sciences}, volume = {24}, number = {9}, pages = {}, pmid = {37175509}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2 ; *Epstein-Barr Virus Infections/complications ; *Papillomavirus Infections/complications ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; *COVID-19/complications ; *Neoplasms/pathology ; Oncogenic Viruses/genetics ; Cell Transformation, Neoplastic ; *Hepatitis C/complications ; }, abstract = {Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, β-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.}, } @article {pmid37174851, year = {2023}, author = {Krysa, JA and Buell, M and Pohar Manhas, K and Kovacs Burns, K and Santana, MJ and Horlick, S and Russell, K and Papathanassoglou, E and Ho, C}, title = {Understanding the Experience of Long COVID Symptoms in Hospitalized and Non-Hospitalized Individuals: A Random, Cross-Sectional Survey Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {37174851}, issn = {2227-9032}, support = {466885/CAPMC/CIHR/Canada ; }, abstract = {The relationship between initial COVID-19 infection and the development of long COVID remains unclear. The purpose of this study was to compare the experience of long COVID in previously hospitalized and non-hospitalized adults in a community-based, cross-sectional telephone survey. Participants included persons with positive COVID-19 test results between 21 March 2021 and 21 October 2021 in Alberta, Canada. The survey included 330 respondents (29.1% response rate), which included 165 previously hospitalized and 165 non-hospitalized individuals. Significantly more previously hospitalized respondents self-reported long COVID symptoms (81 (49.1%)) compared to non-hospitalized respondents (42 (25.5%), p < 0.0001). Most respondents in both groups experienced these symptoms for more than 6 months (hospitalized: 66 (81.5%); non-hospitalized: 25 (59.5), p = 0.06). Hospitalized respondents with long COVID symptoms reported greater limitations on everyday activities from their symptoms compared to non-hospitalized respondents (p < 0.0001) and tended to experience a greater impact on returning to work (unable to return to work-hospitalized: 20 (19.1%); non-hospitalized: 6 (4.5%), p < 0.0001). No significant differences in self-reported long COVID symptoms were found between male and female respondents in both groups (p > 0.05). This study provides novel data to further support that individuals who were hospitalized for COVID-19 appear more likely to experience long COVID symptoms.}, } @article {pmid37174696, year = {2023}, author = {Shevchuk, O and Palii, S and Pak, A and Chantada, N and Seoane, N and Korda, M and Campos-Toimil, M and Álvarez, E}, title = {Vessel-on-a-Chip: A Powerful Tool for Investigating Endothelial COVID-19 Fingerprints.}, journal = {Cells}, volume = {12}, number = {9}, pages = {}, pmid = {37174696}, issn = {2073-4409}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; Lab-On-A-Chip Devices ; }, abstract = {Coronavirus disease (COVID-19) causes various vascular and blood-related reactions, including exacerbated responses. The role of endothelial cells in this acute response is remarkable and may remain important beyond the acute phase. As we move into a post-COVID-19 era (where most people have been or will be infected by the SARS-CoV-2 virus), it is crucial to define the vascular consequences of COVID-19, including the long-term effects on the cardiovascular system. Research is needed to determine whether chronic endothelial dysfunction following COVID-19 could lead to an increased risk of cardiovascular and thrombotic events. Endothelial dysfunction could also serve as a diagnostic and therapeutic target for post-COVID-19. This review covers these topics and examines the potential of emerging vessel-on-a-chip technology to address these needs. Vessel-on-a-chip would allow for the study of COVID-19 pathophysiology in endothelial cells, including the analysis of SARS-CoV-2 interactions with endothelial function, leukocyte recruitment, and platelet activation. "Personalization" could be implemented in the models through induced pluripotent stem cells, patient-specific characteristics, or genetic modified cells. Adaptation for massive testing under standardized protocols is now possible, so the chips could be incorporated for the personalized follow-up of the disease or its sequalae (long COVID) and for the research of new drugs against COVID-19.}, } @article {pmid37174158, year = {2023}, author = {Magnavita, N and Arnesano, G and Di Prinzio, RR and Gasbarri, M and Meraglia, I and Merella, M and Vacca, ME}, title = {Post-COVID Symptoms in Occupational Cohorts: Effects on Health and Work Ability.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {9}, pages = {}, pmid = {37174158}, issn = {1660-4601}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/epidemiology ; Work Capacity Evaluation ; Health Personnel ; *Sleep Initiation and Maintenance Disorders ; Fatigue/epidemiology/etiology ; }, abstract = {Post-acute COVID-19 syndrome is frequently observed in workers and has a substantial impact on work ability. We conducted a health promotion program to identify cases of post-COVID syndrome, analyze the distribution of symptoms and their association with work ability. Of the 1422 workers who underwent routine medical examination in 2021, 1378 agreed to participate. Among the latter, 164 had contracted SARS-CoV-2 and 115 (70% of those who were infected) had persistent symptoms. A cluster analysis showed that most of the post-COVID syndrome cases were characterized by sensory disturbances (anosmia and dysgeusia) and fatigue (weakness, fatigability, tiredness). In one-fifth of these cases, additional symptoms included dyspnea, tachycardia, headache, sleep disturbances, anxiety, and muscle aches. Workers with post-COVID were found to have poorer quality sleep, increased fatigue, anxiety, depression, and decreased work ability compared with workers whose symptoms had rapidly disappeared. It is important for the occupational physician to diagnose post-COVID syndrome in the workplace since this condition may require a temporary reduction in work tasks and supportive treatment.}, } @article {pmid37173355, year = {2023}, author = {Malesevic, S and Sievi, NA and Baumgartner, P and Roser, K and Sommer, G and Schmidt, D and Vallelian, F and Jelcic, I and Clarenbach, CF and Kohler, M}, title = {Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {7717}, pmid = {37173355}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; *Quality of Life/psychology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL. In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George's Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms. Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic. Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.Trial registration: The study is registered on www.ClinicalTrials.gov , NCT04793269.}, } @article {pmid37172813, year = {2023}, author = {Pinto Pereira, SM and Mensah, A and Nugawela, MD and Stephenson, T and Ladhani, SN and Dalrymple, E and Dudley, J and McOwat, K and Simmons, R and Heyman, I and Segal, T and Semple, MG and Xu, L and , and Shafran, R}, title = {Long COVID in Children and Young after Infection or Reinfection with the Omicron Variant: A Prospective Observational Study.}, journal = {The Journal of pediatrics}, volume = {259}, number = {}, pages = {113463}, pmid = {37172813}, issn = {1097-6833}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; COV-LT-0022/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Child ; *Post-Acute COVID-19 Syndrome ; Reinfection ; *COVID-19 ; SARS-CoV-2 ; }, abstract = {To describe the prevalence of long COVID in children infected for the first time (n = 332) or reinfected (n = 243) with Omicron compared with test-negative children (n = 311). Overall, 12%-16% of those infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first positive and reinfected (Pχ2 = 0.17).}, } @article {pmid37172154, year = {2023}, author = {Schmid, DS and Moser, DS and Denecke, K}, title = {Fading Fatigue - A Self-Management App for Supporting Long-COVID Patients with Fatigue.}, journal = {Studies in health technology and informatics}, volume = {301}, number = {}, pages = {67-68}, doi = {10.3233/SHTI230013}, pmid = {37172154}, issn = {1879-8365}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Self-Management ; *Mobile Applications ; *COVID-19 ; Fatigue/therapy ; }, abstract = {Fatigue is the most prevalent Long-COVID symptom. Individuals who are affected have to learn to organize and manage daily activities according to the subjectively perceived energy reserves. Our objective was to develop an application, Fading Fatigue, that supports patients in their energy management, in particular after an initial therapy guided by health professionals. Fading Fatigue was developed in an iterative approach and implemented as a client-server application. Interviews and a literature search were conducted to identify limitations and challenges of the current treatment. Fading Fatigue offers several tools for energy management: a daily energy planner, a documentation aid for well-being and a progress view. Future work should study usability. Inclusion of additional features increasing the adherence such as providing feedback could be considered.}, } @article {pmid37171415, year = {2023}, author = {Ranisavljev, M and Todorovic, N and Ostojic, J and Ostojic, SM}, title = {Reduced tissue creatine levels in patients with long COVID-19: A cross-sectional study.}, journal = {Journal of postgraduate medicine}, volume = {69}, number = {3}, pages = {162-163}, pmid = {37171415}, issn = {0972-2823}, mesh = {Humans ; *Creatine ; Magnetic Resonance Spectroscopy/methods ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Brain/diagnostic imaging ; }, abstract = {Total creatine concentration in the skeletal muscle and brain of long COVID patients were significantly lower when compared to the reference values for the general population, as measured with proton magnetic resonance spectroscopy at 1.5-T in vastus medialis muscle, thalamus, and three bilateral cerebral locations across the white and gray matter.}, } @article {pmid37170616, year = {2023}, author = {Vakani, K and Ratto, M and Sandford-James, A and Antonova, E and Kumari, V}, title = {COVID-19 and cognitive function: Evidence for increased processing speed variability in COVID-19 survivors and multifaceted impairment with long-COVID symptoms.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {66}, number = {1}, pages = {e43}, pmid = {37170616}, issn = {1778-3585}, mesh = {Adult ; Humans ; Processing Speed ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Pandemics ; *Cognition Disorders/psychology ; *COVID-19 ; Cognition ; Survivors ; Neuropsychological Tests ; }, abstract = {BACKGROUND: There is increasing evidence for cognitive function to be negatively impacted by COVID-19. There is, however, limited research evaluating cognitive function pre- and post-COVID-19 using objective measures.

METHODS: We examined processing speed, attention, working memory, executive function and memory in adults (≤69 years) with a history of COVID-19 (n = 129, none acutely unwell), compared to those with no known history of COVID-19 (n = 93). We also examined cognitive changes in a sub-group of COVID (n = 30) and non-COVID (n = 33) participants, compared to their pre-COVID-19 pandemic level.

RESULTS: Cross-sectionally, the COVID group showed significantly larger intra-individual variability in processing speed, compared to the non-COVID group. The COVID sub-group also showed significantly larger intra-individual variability in processing speed, compared to their pre-COVID level; no significant change occurred in non-COVID participants over the same time scale. Other cognitive indices were not significantly impacted in the cross-sectional or within-subjects investigations, but participants (n = 20) who had needed hospitalisation due to COVID-19 showed poor attention and executive function relative to those who had not required hospitalisation (n = 109). Poor health and long-COVID symptoms correlated with poor cognitive function across domains in the COVID group.

CONCLUSIONS: The findings indicate a limited cognitive impact of COVID-19 with only intra-individual variability in processing speed being significantly impacted in an adult UK sample. However, those who required hospitalisation due to COVID-19 severity and/or experience long-COVID symptoms display multifaceted cognitive impairment and may benefit from repeated cognitive assessments and remediation efforts.}, } @article {pmid37170571, year = {2023}, author = {Serrano, MN and Muñoz, OM and Rueda, C and Arboleda, AC and Botero, JD and Bustos, MM}, title = {Factors associated with oxygen requirement and persistent symptoms 1 year after severe COVID-19 infection.}, journal = {The Journal of international medical research}, volume = {51}, number = {5}, pages = {3000605231173317}, pmid = {37170571}, issn = {1473-2300}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology/therapy ; SARS-CoV-2 ; Oxygen/therapeutic use ; Case-Control Studies ; Hospitalization ; }, abstract = {OBJECTIVE: We aimed to describe the prevalence and factors associated with the need for supplemental oxygen and persistent symptoms 1 year after severe SARS-CoV-2 infection.

METHODS: In this historical cohort and nested case-control study, we included adults with severe COVID-19 (requiring admission to the intensive care unit or invasive mechanical ventilation). We evaluated factors associated with a need for supplemental oxygen and persistent symptoms 1 year after severe infection.

RESULTS: We included 135 patients (median age 62 years, 30% women). At 1-year follow-up, the main symptoms were dyspnea (32%), myalgia (9%), cough (7%), anxiety (4%), and depression (5%); 12.59% of patients had prolonged requirement for supplemental oxygen. Factors associated with a persistent requirement for supplemental oxygen were female sex (odds ratio 3.15, 95% confidence interval 1.11-8.90) and Charlson Comorbidity Index > 4 (odds ratio 1.60, 95% confidence interval 1.20-2.12).

CONCLUSIONS: We found that a high prevalence of supplemental oxygen requirement 1 year after severe COVID infection was associated with female sex and a baseline high rate of comorbidities. It is unknown whether this prevalence was related to other factors, such as the altitude at which patients lived. More than half of patients had prolonged post-COVID syndrome.}, } @article {pmid37169323, year = {2025}, author = {Xuereb, RA and Borg, M and Vella, K and Gatt, A and Xuereb, RG and Barbara, C and Fava, S and Magri, CJ}, title = {Long COVID Syndrome: A Case-Control Study.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {131-139}, pmid = {37169323}, issn = {1555-7162}, mesh = {Humans ; Female ; Male ; Middle Aged ; Case-Control Studies ; *COVID-19/complications ; *Post-Acute COVID-19 Syndrome ; *Quality of Life ; Adult ; Dyspnea/etiology ; SARS-CoV-2 ; Fatigue/etiology ; C-Reactive Protein/analysis ; Follow-Up Studies ; }, abstract = {BACKGROUND: Acute coronavirus disease 2019 (COVID-19) causes various cardiovascular complications. However, it is unknown if there are cardiovascular sequelae in the medium and long-term. The aim of this study was dual. Firstly, we wanted to investigate symptomatology and health-related quality of life (HRQoL) at medium-term follow-up (6 months post-COVID). Secondly, we wanted to assess whether history of COVID-19 and persistent shortness of breath at medium-term follow-up are associated with ongoing inflammation, endothelial dysfunction, and cardiac injury.

METHODS: A case-control study was performed. Virologically proven COVID-19 cases and age- and gender-matched controls were interviewed to assess symptoms and HRQoL. Biochemical tests were also performed.

RESULTS: The study comprised 174 cases and 75 controls. The mean age of the participants was 46.1±13.8 years. The median follow-up was 173.5 days (interquartile range 129-193.25 days). There was no significant difference in the demographics between cases and controls. At follow-up, cases had a higher frequency of shortness of breath, fatigue, arthralgia, abnormal taste of food (P <.001), and anosmia. Cases also exhibited worse scores in the general health and role physical domains of the Short Form Survey-36. High-sensitivity C-reactive protein (hsCRP) was significantly higher in the cases, and there was a positive correlation of hsCRP with time. Significant determinants of shortness of breath were age, female gender and white cell count, troponin I, and lower hemoglobin levels at follow-up.

CONCLUSION: Post-COVID-19 patients have persistent symptomatology at medium-term follow-up. Higher hsCRP in cases and the positive association of hsCRP with time suggest ongoing systemic inflammation in patients persisting for months after COVID-19.}, } @article {pmid37168268, year = {2023}, author = {Augustin, M and Heyn, F and Ullrich, S and Sandaradura de Silva, U and Albert, MC and Linne, V and Schlotz, M and Schommers, P and Pracht, E and Horn, C and Suarez, I and Simonis, A and Picard, LK and Zoufaly, A and Wenisch, C and Fätkenheuer, G and Gruell, H and Klein, F and Hallek, M and Walczak, H and Rybniker, J and Theobald, SJ and Lehmann, C}, title = {Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1129288}, pmid = {37168268}, issn = {2296-858X}, abstract = {BACKGROUND: Symptoms lasting longer than 12 weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.

METHODS: Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.

RESULTS: Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4[+] and CD8[+] T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3[+]) and IL-4 were more abundant in PCS[+].

CONCLUSION: This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.}, } @article {pmid37168008, year = {2023}, author = {Alabsi, H and Emerson, K and Lin, DJ}, title = {Neurorecovery after Critical COVID-19 Illness.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {312-320}, doi = {10.1055/s-0043-1768714}, pmid = {37168008}, issn = {1098-9021}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases/diagnosis/etiology/therapy ; Acute Disease ; }, abstract = {With the hundreds of millions of people worldwide who have been, and continue to be, affected by pandemic coronavirus disease (COVID-19) and its chronic sequelae, strategies to improve recovery and rehabilitation from COVID-19 are critical global public health priorities. Neurologic complications have been associated with acute COVID-19 infection, usually in the setting of critical COVID-19 illness. Neurologic complications are also a core feature of the symptom constellation of long COVID and portend poor outcomes. In this article, we review neurologic complications and their mechanisms in critical COVID-19 illness and long COVID. We focus on parallels with neurologic disease associated with non-COVID critical systemic illness. We conclude with a discussion of how recent findings can guide both neurologists working in post-acute neurologic rehabilitation facilities and policy makers who influence neurologic resource allocation.}, } @article {pmid37167361, year = {2023}, author = {Tsai, EJ and Cˇiháková, D and Tucker, NR}, title = {Cell-Specific Mechanisms in the Heart of COVID-19 Patients.}, journal = {Circulation research}, volume = {132}, number = {10}, pages = {1290-1301}, pmid = {37167361}, issn = {1524-4571}, support = {R01 HL138528/HL/NHLBI NIH HHS/United States ; R01 HL118183/HL/NHLBI NIH HHS/United States ; R01 HL136586/HL/NHLBI NIH HHS/United States ; K01 HL140187/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Myocarditis ; Endothelial Cells ; Hospital Mortality ; Post-Acute COVID-19 Syndrome ; Heart ; *Heart Diseases ; Troponin ; Myocytes, Cardiac ; }, abstract = {From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation, the greater the COVID-19 illness severity and in-hospital death risk. Whether these consequences were due to direct SARS-CoV-2 infection of cardiac cells or secondary to inflammatory responses steered early cardiac autopsy studies. SARS-CoV-2 was reportedly detected in endothelial cells, cardiac myocytes, and within the extracellular space. However, findings were inconsistent and different methodologies had their limitations. Initial autopsy reports suggested that SARS-CoV-2 myocarditis was common, setting off studies to find and phenotype inflammatory infiltrates in the heart. Nonetheless, subsequent studies rarely detected myocarditis. Microthrombi, cardiomyocyte necrosis, and inflammatory infiltrates without cardiomyocyte damage were much more common. In vitro and ex vivo experimental platforms have assessed the cellular tropism of SARS-CoV-2 and elucidated mechanisms of viral entry into and replication within cardiac cells. Data point to pericytes as the primary target of SARS-CoV-2 in the heart. Infection of pericytes can account for the observed pericyte and endothelial cell death, innate immune response, and immunothrombosis commonly observed in COVID-19 hearts. These processes are bidirectional and synergistic, rendering a definitive order of events elusive. Single-cell/nucleus analyses of COVID-19 myocardial tissue and isolated cardiac cells have provided granular data about the cellular composition and cell type-specific transcriptomic signatures of COVID-19 and microthrombi-positive COVID-19 hearts. Still, much remains unknown and more in vivo studies are needed. This review seeks to provide an overview of the current understanding of COVID-19 cardiac pathophysiology. Cell type-specific mechanisms and the studies that provided such insights will be highlighted. Given the unprecedented pace of COVID-19 research, more mechanistic details are sure to emerge since the writing of this review. Importantly, our current knowledge offers significant clues about the cardiac pathophysiology of long COVID-19, the increased postrecovery risk of cardiac events, and thus, the future landscape of cardiovascular disease.}, } @article {pmid37167353, year = {2023}, author = {Chappell, MC}, title = {Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.}, journal = {Circulation research}, volume = {132}, number = {10}, pages = {1320-1337}, pmid = {37167353}, issn = {1524-4571}, support = {R01 HL146818/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Renin-Angiotensin System/physiology ; *COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Peptidyl-Dipeptidase A/physiology ; SARS-CoV-2 ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; }, abstract = {The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT1 AT2 and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.}, } @article {pmid37167167, year = {2022}, author = {Tanashyan, MM and Raskurazhev, AA and Kuznetsova, PI and Bely, PA and Zaslavskaya, KI}, title = {[Prospects and possibilities for the treatment of patients with long COVID-19 syndrome].}, journal = {Terapevticheskii arkhiv}, volume = {94}, number = {11}, pages = {1285-1293}, doi = {10.26442/00403660.2022.11.201981}, pmid = {37167167}, issn = {0040-3660}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Asthenia/drug therapy/etiology ; Prospective Studies ; *COVID-19 ; Fatigue ; Double-Blind Method ; Treatment Outcome ; }, abstract = {AIM: To study the efficacy and safety of a drug product based on the succinic acid complex with trimethylhydrazine used to treat patients with asthenic syndrome after a new coronavirus infection (COVID-19).

MATERIALS AND METHODS: A prospective, multicenter, comparative, randomized, double-blind, placebo-controlled study of the safety and efficacy of sequential therapy with Brainmax[®] enrolled 160 patients 12-16 weeks after coronavirus infection (no more than 12 months). The study was conducted at 6 healthcare centers in different regions of the Russian Federation. At the enrollment, clinical and neurological examination and the following tests were performed: complete blood count, urinalysis, blood chemistry, coagulation test, pulse oximetry, electrocardiography, glomerular filtration rate calculation (according to Cockcroft-Gault formula) were performed. Also, the patients were assessed using the following tools: VAS headache rating scale, MFI-20 asthenia scale, PSQI index, FAS-10 fatigue assessment scale, Dizziness Handicap Inventory (DHI), MoCA-test for cognitive impairment assessment, Beck Anxiety Inventory, Kérdö Autonomic Index.

RESULTS: The primary endpoint was the mean reduction in the MFI-20 asthenia scale score after the therapy (Visit 5, 41st day of therapy) compared to data from Visit 0 (beginning of therapy). A clinically significant advantage of the study drug versus the placebo was demonstrated, with a median absolute change in the MFI-20 score of -19.5 [-27; -11] points in the Brainmax[®] drug group and -3 [-7; 1] score in the placebo group (p<0.001). A significant sleep quality improvement according to the PSQI index was shown in the study group: by -2.5 [-4; -1] points versus no improvement in the placebo group (0 [-3; 0], p<0,001). Significant differences were also noted for the following secondary endpoints: PSQI sleep quality scale, FAS-10 fatigue assessment scale, DHI, and Beck Anxiety and Depression Inventory. There was also a decrease in patients' complaints of cognitive deterioration according to the CGI scale.

CONCLUSION: Our study clearly demonstrated the efficacy and high safety profile of Brainmax[®] in a representative sample of patients with the post-COVID syndrome.}, } @article {pmid37167117, year = {2023}, author = {Zhuravleva, MV and Chulanov, VP and Gagarina, JV and Shabalina, EA}, title = {[Pharmacoeconomic evaluation of the tixagevimab and cilgavimab combination using for pre-exposure prophylaxis of COVID-19].}, journal = {Terapevticheskii arkhiv}, volume = {95}, number = {1}, pages = {66-77}, doi = {10.26442/00403660.2023.01.202065}, pmid = {37167117}, issn = {0040-3660}, mesh = {Humans ; Child ; *COVID-19/prevention & control ; Economics, Pharmaceutical ; *Pre-Exposure Prophylaxis ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIM: To evaluate pharmacoeconomic feasibility using of the tixagevimab and cilgavimab combination for pre-exposure prophylaxis of COVID-19 in immunocompromised patients.

MATERIALS AND METHODS: Cost-effectiveness of tixagevimab and cilgavimab in persons ≥12 years old who weigh ≥40 kg and have either a history of allergy that prevents their vaccination against COVID-19 or moderate or immunocompromised was assessed based on PROVENT phase III study results. The quantity of life years or quality-adjusted life years gained was calculated. Direct medical cost associated with prophylaxis of COVID-19, treatment of infected patients and those experiencing long COVID post infection were assessed. Results were compared with wiliness-to-pay threshold, measured as tripled gross domestic product per capita and equal to 2.69 mln RUB in 2022.

RESULTS: Pre-exposure prophylaxis of COVID-19 results in additional 0.0287 life years or 0.0247 quality-adjusted life years. The cost of additional life year gained is equal to 1.12 mln RUB, the cost of additional quality-adjusted life years is 1.30 mln RUB. Both costs of additional life year and cost of quality-adjusted life years appeared to be significantly less compared to wiliness-to-pay threshold.

CONCLUSION: Pre-exposure prophylaxis of COVID-19 with combination of tixagevimab and cilgavimab is economically feasible and may be recommended for wide use in Russian healthcare system.}, } @article {pmid37166330, year = {2023}, author = {L Mandel, H and Colleen, G and Abedian, S and Ammar, N and Charles Bailey, L and Bennett, TD and Daniel Brannock, M and Brosnahan, SB and Chen, Y and Chute, CG and Divers, J and Evans, MD and Haendel, M and Hall, MA and Hirabayashi, K and Hornig, M and Katz, SD and Krieger, AC and Loomba, J and Lorman, V and Mazzotti, DR and McMurry, J and Moffitt, RA and Pajor, NM and Pfaff, E and Radwell, J and Razzaghi, H and Redline, S and Seibert, E and Sekar, A and Sharma, S and Thaweethai, T and Weiner, MG and Jae Yoo, Y and Zhou, A and Thorpe, LE}, title = {Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative.}, journal = {Sleep}, volume = {46}, number = {9}, pages = {}, pmid = {37166330}, issn = {1550-9109}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; Child ; *COVID-19/complications/diagnosis/epidemiology ; Electronic Health Records ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Disease Progression ; Risk Factors ; *Sleep Apnea, Obstructive/complications/diagnosis/epidemiology ; }, abstract = {STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC).

METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities.

RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis.

CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.}, } @article {pmid37166260, year = {2023}, author = {Cazé, AB and Cerqueira-Silva, T and Bomfim, AP and de Souza, GL and Azevedo, AC and Brasil, MQ and Santos, NR and Khouri, R and Dan, J and Bandeira, AC and Cavalcanti, LP and Barral-Netto, M and Barral, A and Barbosa, CG and Boaventura, VS}, title = {Prevalence and risk factors for long COVID after mild disease: A cohort study with a symptomatic control group.}, journal = {Journal of global health}, volume = {13}, number = {}, pages = {06015}, pmid = {37166260}, issn = {2047-2986}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Cohort Studies ; Quality of Life ; Prevalence ; Control Groups ; Risk Factors ; }, abstract = {BACKGROUND: There is limited data on the prevalence and risk factors for long COVID and few prospective studies with appropriate control groups and adequate sample sizes. We performed a prospective study to determine the prevalence and risk factors for long COVID.

METHODS: We recruited individuals aged ≥15 years who were clinically suspected of having an acute SARS-CoV-2 infection from September 2020 to April 2021. We collected nasopharyngeal swabs three to five days following symptom onset for analysing using reverse transcriptase polymerase chain reaction (RT-PCR). We also collected clinical and sociodemographic characteristics from both SARS-CoV-2 positive and negative participants using structured questionnaires. We followed-up the participants via telephone interview to assess early outcomes and persistent symptoms. For COVID-19 cases, 5D-3L EuroQol questionnaire was used to assess the impact of symptoms on quality of life.

RESULTS: We followed 814 participants (412 COVID-19 positive and 402 COVID-19 negative persons). Most (n = 741/814) had mild symptoms. Both groups had similar sociodemographic and clinical characteristics, except for the hospitalization rate (15.8% in the COVID-19 positive vs 1.5% in the COVID-19 negative group). One month after disease onset, 122/412 (29.6%) individuals in the COVID-19 positive (long COVID) and 24 (6%) in the COVID-19 negative group reported residual symptoms. In the long COVID group, fatigue, olfactory disorder, and myalgia were the most frequent symptoms in the acute phase. Compared to recovered individuals, older age and having more than five symptoms during the acute phase were risk factors for long COVID. Quality of life was evaluated in 102 out of 122 cases of long COVID, with 57 (55.9%) reporting an impact in at least one dimension of the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L) questionnaire.

CONCLUSIONS: In this prospective study consisting predominantly of individuals with mild disease, the persistence of symptoms after an acute respiratory illness was associated with a diagnosis of COVID-19. Polysymptomatic acute disease and older age were risk factors for long COVID.}, } @article {pmid37166076, year = {2023}, author = {Durstenfeld, MS and Peluso, MJ and Kaveti, P and Hill, C and Li, D and Sander, E and Swaminathan, S and Arechiga, VM and Lu, S and Goldberg, SA and Hoh, R and Chenna, A and Yee, BC and Winslow, JW and Petropoulos, CJ and Kelly, JD and Glidden, DV and Henrich, TJ and Martin, JN and Lee, YJ and Aras, MA and Long, CS and Grandis, DJ and Deeks, SG and Hsue, PY}, title = {Reduced Exercise Capacity, Chronotropic Incompetence, and Early Systemic Inflammation in Cardiopulmonary Phenotype Long Coronavirus Disease 2019.}, journal = {The Journal of infectious diseases}, volume = {228}, number = {5}, pages = {542-554}, pmid = {37166076}, issn = {1537-6613}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; L30 HL159695/HL/NHLBI NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Male ; Humans ; *Exercise Tolerance ; Contrast Media ; Heart Rate ; *COVID-19 ; SARS-CoV-2 ; Gadolinium ; Inflammation ; Phenotype ; }, abstract = {BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

METHODS: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers.

RESULTS: Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1-8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent.

CONCLUSIONS: Cardiopulmonary symptoms >1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with "long COVID."}, } @article {pmid37165680, year = {2024}, author = {Zorlu, SA and Oz, A}, title = {A Novel Combined Model to Predict the Prognosis of COVID-19: Radiologicalmetabolic Scoring.}, journal = {Current medical imaging}, volume = {20}, number = {}, pages = {e110523216780}, doi = {10.2174/1573405620666230511093259}, pmid = {37165680}, issn = {1573-4056}, mesh = {Humans ; Retrospective Studies ; *COVID-19/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Prognosis ; }, abstract = {AIM: To investigate the performance of a novel radiological-metabolic scoring (RM-S) system to predict mortality and intensive care unit (ICU) requirements among COVID-19 patients and to compare performance with the chest computed-tomography severity-scoring (C-CT-SS). The RMS was created from scoring systems such as visual coronary-artery-calcification scoring (V-CAC-S), hepatic-steatosis scoring (HS-S) and pancreatic-steatosis scoring (PS-S).

METHODS: Between May 2021 and January 2022, 397 patients with COVID-19 were included in this retrospective cohort study. All demographic, clinical and laboratory data and chest CT images of patients were retrospectively reviewed. RM-S, V-CAC-S, HS-S, PS-S and C-CT-SS scores were calculated, and their performance in predicting mortality and ICU requirement were evaluated by univariate and multivariable analyses.

RESULTS: A total of 32 (8.1%) patients died, and 77 (19.4%) patients required ICU admission. Mortality and ICU admission were both associated with older age (p < 0.001). Sex distribution was similar in the deceased vs. survivor and ICU vs. non-ICU comparisons (p = 0.974 and p = 0.626, respectively). Multiple logistic regression revealed that mortality was independently associated with having a C-CT-SS score of ≥ 14 (p < 0.001) and severe RM-S category (p = 0.010), while ICU requirement was independently associated with having a C-CT-SS score of ≥ 14 (p < 0.001) and severe V-CAC-S category (p = 0.010).

CONCLUSION: RM-S, C-CT-SS, and V-CAC-S are useful tools that can be used to predict patients with poor prognoses for COVID-19. Long-term prospective follow-up of patients with high RM-S scores can be useful for predicting long COVID.}, } @article {pmid37164340, year = {2023}, author = {Sorrell, TC and Hensher, M and Sanci, LA}, title = {Long COVID in Australia: achieving equitable access to supportive health care.}, journal = {The Medical journal of Australia}, volume = {218}, number = {10}, pages = {455-457}, doi = {10.5694/mja2.51950}, pmid = {37164340}, issn = {1326-5377}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Health Services Accessibility ; Australia/epidemiology ; }, } @article {pmid37164035, year = {2023}, author = {Shabnam, S and Razieh, C and Dambha-Miller, H and Yates, T and Gillies, C and Chudasama, YV and Pareek, M and Banerjee, A and Kawachi, I and Lacey, B and Morris, EJ and White, M and Zaccardi, F and Khunti, K and Islam, N}, title = {Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom.}, journal = {Journal of the Royal Society of Medicine}, volume = {116}, number = {8}, pages = {263-273}, pmid = {37164035}, issn = {1758-1095}, support = {MC_UU_00006/7/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Health Status Disparities ; Cohort Studies ; United Kingdom/epidemiology ; Surveys and Questionnaires ; Socioeconomic Factors ; }, abstract = {OBJECTIVES: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation.

DESIGN: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID.

SETTING: Community-based survey in the UK.

PARTICIPANTS: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

MAIN OUTCOME MEASURES: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation.

RESULTS: Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51).

CONCLUSIONS: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.}, } @article {pmid37163472, year = {2023}, author = {Ridge, D and Pilkington, K and Donovan, S and Moschopoulou, E and Gopal, D and Bhui, K and Chalder, T and Khan, I and Korszun, A and Taylor, S and , }, title = {A meta-ethnography investigating relational influences on mental health and cancer-related health care interventions for racially minoritised people in the UK.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0284878}, pmid = {37163472}, issn = {1932-6203}, support = {RP-PG-0616-20002/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Mental Health ; *COVID-19 ; Systematic Reviews as Topic ; Anthropology, Cultural ; Delivery of Health Care ; United Kingdom ; *Neoplasms/therapy ; }, abstract = {OBJECTIVE: Despite calls to increase the 'cultural competence' of health care providers, racially minoritised people continue to experience a range of problems when it comes to health care, including discrimination. While relevant qualitative meta-syntheses have suggested better ways forward for health care for racialised minorities, many have lacked conceptual depth, and none have specifically investigated the relational dimensions involved in care. We set out to investigate the social and cultural influences on health care interventions, focusing on psychological approaches and/or cancer care to inform the trial of a new psychological therapy for those living with or beyond cancer.

METHOD: A meta-ethnography approach was used to examine the relevant qualitative studies, following Noblit and Hare, and guided by patient involvement throughout. Papers were analysed between September 2018 and February 2023, with some interruptions caused by the Covid pandemic. The following databases were searched: Ovid MEDLINE, EBSCO CINAHL, Ovid Embase, EBSCO PsycINFO, Proquest Sociology Collection (including Applied Social Sciences Index & Abstracts (ASSIA), Sociological Abstracts and Sociology Database), EBSCO SocINDEX, Ovid AMED, and Web of Science. The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42018107695), and reporting follows the eMERGe Reporting Guidance for meta-ethnographies (France et al. 2019).

RESULTS: Twenty-nine journal papers were included in the final review. Themes (third-order constructs) developed in the paper include the centrality of the patient-practitioner relationship; how participants give meaning to their illness in connection to others; how families (rather than individuals) may make health decisions; how links with a higher power and spiritual/religious others can play a role in coping; and the ways in which a hierarchy of help-seeking develops, frequently with the first port of call being the resources of oneself. Participants in studies had a need to avoid being 'othered' in their care, valuing practitioners that connected with them, and who were able to recognise them as whole and complex (sometimes described in relational languages like 'love'). Complex family-based health decision-making and/or the importance of relations with non-human interactants (e.g. God, spiritual beings) were frequently uncovered, not to mention the profoundly emergent nature of stigma, whereby families could be relatively safe havens for containing and dealing with health challenges. A conceptual framework of 'animated via (frequently hidden) affective relationality' emerged in the final synthesis, bringing all themes together, and drawing attention to the emergent nature of the salient issues facing minoritised patients in health care interactions.

CONCLUSION: Our analysis is important because it sheds light on the hitherto buried relational forces animating and producing the specific issues facing racially minoritised patients, which study participants thought were largely overlooked, but to which professionals can readily relate (given the universal nature of human relations). Thus, training around the affective relationality of consultations could be a fruitful avenue to explore to improve care of diverse patients.}, } @article {pmid37163427, year = {2023}, author = {Wei, ZD and Liang, K and Shetty, AK}, title = {Complications of COVID-19 on the Central Nervous System: Mechanisms and Potential Treatment for Easing Long COVID.}, journal = {Aging and disease}, volume = {14}, number = {5}, pages = {1492-1510}, pmid = {37163427}, issn = {2152-5250}, support = {R01 NS106907/NS/NINDS NIH HHS/United States ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades human cells by binding to the angiotensin-converting-enzyme-2 (ACE-2) using a spike protein and leads to Coronavirus disease-2019 (COVID-19). COVID-19 primarily causes a respiratory infection that can lead to severe systemic inflammation. It is also common for some patients to develop significant neurological and psychiatric symptoms. The spread of SARS-CoV-2 to the CNS likely occurs through several pathways. Once spread in the CNS, many acute symptoms emerge, and such infections could also transpire into severe neurological complications, including encephalitis or ischemic stroke. After recovery from the acute infection, a significant percentage of patients develop "long COVID," a condition in which several symptoms of COVID-19 persist for prolonged periods. This review aims to discuss acute and chronic neurological problems after SARS-CoV-2 infection. The potential mechanisms by which SARS-CoV-2 enters the CNS and causes neuroinflammation, neuropathological changes observed in post-mortem brains of COVID-19 patients, and cognitive and mood problems in COVID-19 survivors are discussed in the initial part. The later part of the review deliberates the causes of long COVID, approaches for noninvasive tracking of neuroinflammation in long COVID patients, and the potential therapeutic strategies that could ease enduring CNS symptoms observed in long COVID.}, } @article {pmid37163246, year = {2023}, author = {Marcus, R}, title = {New Alzheimer Disease Drugs, Long COVID and the Central Nervous System, and a Nasal Spray for Migraines-Highlights From the 2023 American Academy of Neurology Conference.}, journal = {JAMA}, volume = {329}, number = {21}, pages = {1811-1813}, doi = {10.1001/jama.2023.4389}, pmid = {37163246}, issn = {1538-3598}, mesh = {Humans ; *Alzheimer Disease/drug therapy ; Central Nervous System/physiopathology ; COVID-19/complications/physiopathology ; *Migraine Disorders/drug therapy ; Nasal Sprays ; Nervous System Diseases/etiology/physiopathology ; *Post-Acute COVID-19 Syndrome/complications/physiopathology ; }, } @article {pmid37162923, year = {2023}, author = {Metz, TD and Clifton, RG and Gallagher, R and Gross, RS and Horwitz, LI and Jacoby, VL and Martin-Herz, SP and Peralta-Carcelen, M and Reeder, HT and Beamon, CJ and Bind, MA and Chan, J and Chang, AA and Chibnik, LB and Costantine, MM and Fitzgerald, ML and Foulkes, AS and Gibson, KS and Güthe, N and Habli, M and Hackney, DN and Hoffman, MK and Hoffman, MC and Hughes, BL and Katz, SD and Laleau, V and Mallett, G and Mendez-Figueroa, H and Monzon, V and Palatnik, A and Palomares, KTS and Parry, S and Peralta-Carcelen, M and Pettker, CM and Plunkett, BA and Poppas, A and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Schlater, SM and Sciurba, FC and Simhan, HN and Skupski, DW and Sowles, A and Thaweethai, T and Thomas, GL and Thorp, JM and Tita, AT and Weiner, SJ and Weigand, S and Yee, LM and Flaherman, VJ}, title = {Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37162923}, support = {U10 HD040500/HD/NICHD NIH HHS/United States ; UG1 HD027869/HD/NICHD NIH HHS/United States ; UG1 HD087230/HD/NICHD NIH HHS/United States ; UM1 TR004409/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; OT2 HL161841/HL/NHLBI NIH HHS/United States ; UG1 HD040500/HD/NICHD NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UG1 HD027915/HD/NICHD NIH HHS/United States ; UG1 HD087192/HD/NICHD NIH HHS/United States ; UG1 HD040544/HD/NICHD NIH HHS/United States ; UG1 HD034208/HD/NICHD NIH HHS/United States ; }, abstract = {IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.

METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.

DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.

REGISTRATION: NCT05172024.}, } @article {pmid37162150, year = {2023}, author = {Kavanagh, KT and Maiwald, M and Pontus, C and Cimiotti, JP and Palmieri, PA and Cormier, LE}, title = {Frontline Worker Safety in the Age of COVID-19: A Global Perspective.}, journal = {Journal of patient safety}, volume = {19}, number = {5}, pages = {293-299}, pmid = {37162150}, issn = {1549-8425}, mesh = {Child ; Humans ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Public Health ; Masks ; }, abstract = {The third annual Health Watch USA sm webinar conference assembled 16 speakers from 4 continents who shared information regarding frontline worker safety in the age of COVID-19. The U.S. Bureau of Labor Statistics reported a nearly 4000% increase in workplace illness in 2020 compared with 2019. It is estimated that 2% of the U.S. workforce is not working because of long COVID. In addition, the impact is growing with each surge. After the acute illness, patients are often described as recovered, when in fact many have only survived and are coping with the multisystem impacts of long COVID. Long COVID, including its late cognitive, cardiovascular, embolic, and diabetic complications, disproportionately impacts frontline workers, many of whom are of lower socioeconomic status and represented by ethnic minorities. Natural infection and current vaccines do not provide durable protection for reinfection. Herd immunity is not possible at this time. Although SARS-CoV-2 is unlikely to be eliminated, decreasing spread is imperative to slow the rate of mutations, decrease the number of reinfections, and lower the chances of developing long COVID. The primary mode of spread is through aerosolization. Both routine breathing and talking aerosolizes the virus. With the extremely high infectivity of SARS-CoV-2, it is unlikely that central building ventilation alone will be enough to satisfactorily mitigate spread. Additional safe active air cleaning technology, such as upper-room germicidal UV-C lighting, needs to be deployed. Misinformation and disinformation have inhibited response effectiveness. Examples include downplaying the benefit of well-fitted masks and the risks that COVID-19 and long COVID pose to children, along with believing children cannot spread the disease. The engagement of local community leaders is essential to educate the community and drive social change to accept vaccinations and other public health interventions. Vaccinations and natural immunity alone are unlikely to adequately prevent community spread and do not provide durable protection against the risk of long COVID. Frontline workers must keep their immunity as high as possible and work in settings with clean air, along with wearing N95 masks when they are in contact with the public. Finally, there needs to be a financial safety net for frontline workers and their families in the event of incapacitation or death from COVID-19.}, } @article {pmid37161609, year = {2023}, author = {Spatola, M and Nziza, N and Jung, W and Deng, Y and Yuan, D and Dinoto, A and Bozzetti, S and Chiodega, V and Ferrari, S and Lauffenburger, DA and Mariotto, S and Alter, G}, title = {Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses.}, journal = {Brain : a journal of neurology}, volume = {146}, number = {10}, pages = {4292-4305}, pmid = {37161609}, issn = {1460-2156}, support = {U19 AI135995/AI/NIAID NIH HHS/United States ; R03 AR078938/AR/NIAMS NIH HHS/United States ; K23 AR073334/AR/NIAMS NIH HHS/United States ; P30 AR072577/AR/NIAMS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; R01 AI146785/AI/NIAID NIH HHS/United States ; R01 NS122570/NS/NINDS NIH HHS/United States ; P30 AR070253/AR/NIAMS NIH HHS/United States ; R01 AR077607/AR/NIAMS NIH HHS/United States ; R37 AI080289/AI/NIAID NIH HHS/United States ; U01 CA260476/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Aged ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Immunoglobulin G ; Immunoglobulin M ; }, abstract = {Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the CNS, can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations and persistence of SARS-CoV-2 reservoirs. In this prospective cohort study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common coronaviruses: 229E, HKU1, NL63 and OC43) in the serum and CSF from 112 infected individuals who developed (n = 18) or did not develop (n = 94) neuroPASC. Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC compared with serum responses. All antibody isotypes (IgG, IgM, IgA) and subclasses (IgA1-2, IgG1-4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favour of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Compared to individuals who did not develop post-acute complications following infection, individuals with neuroPASC had similar demographic features (median age 65 versus 66.5 years, respectively, P = 0.55; females 33% versus 44%, P = 0.52) but exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fcγ receptors. However, surprisingly, neuroPASC individuals showed significantly expanded antibody responses to other common coronaviruses, including 229E, HKU1, NL63 and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting an 'original antigenic sin' (or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to the current infection, as a key prognostic marker of neuroPASC disease. Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection.}, } @article {pmid37158440, year = {2023}, author = {Nikolich, JŽ and Rosen, CJ}, title = {Toward Comprehensive Care for Long Covid.}, journal = {The New England journal of medicine}, volume = {388}, number = {23}, pages = {2113-2115}, doi = {10.1056/NEJMp2304550}, pmid = {37158440}, issn = {1533-4406}, mesh = {Humans ; COVID-19 ; *Post-Acute COVID-19 Syndrome/therapy ; SARS-CoV-2 ; Comprehensive Health Care ; }, } @article {pmid37156258, year = {2023}, author = {Al-Aly, Z}, title = {Prevention of long COVID: progress and challenges.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {7}, pages = {776-777}, pmid = {37156258}, issn = {1474-4457}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; }, } @article {pmid37156053, year = {2023}, author = {Sarkanen, T and Partinen, M and Bjorvatn, B and Merikanto, I and Benedict, C and Nadorff, MR and Bolstad, CJ and Espie, C and Matsui, K and Chung, F and Morin, CM and Wing, YK and Penzel, T and Macêdo, T and Mota-Rolim, S and Holzinger, B and Plazzi, G and De Gennaro, L and Landtblom, AM and Inoue, Y and Sieminski, M and Leger, D and Dauvilliers, Y}, title = {Association between hypersomnolence and the COVID-19 pandemic: The International COVID-19 Sleep Study (ICOSS).}, journal = {Sleep medicine}, volume = {107}, number = {}, pages = {108-115}, pmid = {37156053}, issn = {1878-5506}, mesh = {Humans ; Female ; Adult ; Male ; Pandemics ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/complications ; *Disorders of Excessive Somnolence/diagnosis ; Fatigue/epidemiology/complications ; Sleep ; }, abstract = {BACKGROUND: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear.

METHODS: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and excessive quantity of sleep (EQS), as well as sociodemographic factors, sleep patterns, psychological symptoms, and quality of life was distributed in 15 countries across the world from May to September in 2020.

RESULTS: Altogether responses from 18,785 survey participants (65% women, median age 39 years) were available for analysis. Only 2.8% reported having had COVID-19. Compared to before the pandemic, the prevalence of EDS, EQS, and fatigue increased from 17.9% to 25.5%, 1.6%-4.9%, and 19.4%-28.3% amid the pandemic, respectively. In univariate logistic regression models, reports of having a COVID-19 were associated with EQS (OR 5.3; 95%-CI 3.6-8.0), EDS (2.6; 2.0-3.4), and fatigue (2.8; 2.1-3.6). In adjusted multivariate logistic regression, sleep duration shorter than desired (3.9; 3.2-4.7), depressive symptoms (3.1; 2.7-3.5), use of hypnotics (2.3; 1.9-2.8), and having reported COVID-19 (1.9; 1.3-2.6) remained strong predictors of EDS. Similar associations emerged for fatigue. In the multivariate model, depressive symptoms (4.1; 3.6-4.6) and reports of having COVID-19 (2.0; 1.4-2.8) remained associated with EQS.

CONCLUSIONS: A large increase in EDS, EQS, and fatigue occurred due to the COVID-19 pandemic, and especially in self-reported cases of COVID-19. These findings warrant a thorough understanding of their pathophysiology to target prevention and treatment strategies for long COVID condition.}, } @article {pmid37155736, year = {2023}, author = {Kuut, TA and Müller, F and Csorba, I and Braamse, A and Aldenkamp, A and Appelman, B and Assmann-Schuilwerve, E and Geerlings, SE and Gibney, KB and Kanaan, RAA and Mooij-Kalverda, K and Olde Hartman, TC and Pauëlsen, D and Prins, M and Slieker, K and van Vugt, M and Keijmel, SP and Nieuwkerk, P and Rovers, CP and Knoop, H}, title = {Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {5}, pages = {687-695}, pmid = {37155736}, issn = {1537-6591}, mesh = {Humans ; Quality of Life ; *COVID-19/complications ; *Cognitive Behavioral Therapy/methods ; Netherlands ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19.

METHODS: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU.

RESULTS: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded.

CONCLUSIONS: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up.

CLINICAL TRIALS REGISTRATION: Netherlands Trial Register NL8947.}, } @article {pmid37155451, year = {2023}, author = {Thor, DC and Suarez, S}, title = {Corona With Lyme: A Long COVID Case Study.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36624}, pmid = {37155451}, issn = {2168-8184}, abstract = {The longevity of the coronavirus disease 2019 (COVID-19) pandemic has necessitated continued discussion about the long-term impacts of SARS-CoV-2 infection. Many who develop an acute COVID-19 infection will later face a constellation of enduring symptoms of varying severity, otherwise known as long COVID. As the pandemic reaches its inevitable endemicity, the long COVID patient population will undoubtedly grow and require improved recognition and management. The case presented describes the three-year arc of a previously healthy 26-year-old female medical student from initial infection and induction of long COVID symptomology to near-total remission of the disease. In doing so, the course of this unique post-viral illness and the trials and errors of myriad treatment options will be chronologized, thereby contributing to the continued demand for understanding this mystifying disease.}, } @article {pmid37154433, year = {2023}, author = {Finsterer, J and Mehri, S}, title = {Post-COVID 'brain fog' will clear up only through neuropsychological examination.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {3}, pages = {322-323}, doi = {10.5603/PJNNS.a2023.0032}, pmid = {37154433}, issn = {0028-3843}, mesh = {Humans ; *COVID-19 ; Neuropsychological Tests ; Brain ; }, } @article {pmid37154432, year = {2023}, author = {Chatys-Bogacka, Ż and Mazurkiewicz, I and Słowik, J and Nowak, K and Sydor, W and Wizner, B and Słowik, A and Wnuk, M and Drabik, L}, title = {Response to Letter to the Editors regarding article entitled 'Sex-related patient-reported brain fog symptoms in nonhospitalised COVID-19 patients'.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {3}, pages = {326-327}, doi = {10.5603/PJNNS.a2023.0033}, pmid = {37154432}, issn = {0028-3843}, mesh = {Humans ; *COVID-19 ; Patient Reported Outcome Measures ; Brain ; }, } @article {pmid37153597, year = {2023}, author = {Perumal, R and Shunmugam, L and Naidoo, K and Abdool Karim, SS and Wilkins, D and Garzino-Demo, A and Brechot, C and Parthasarathy, S and Vahlne, A and Nikolich, JŽ}, title = {Long COVID: a review and proposed visualization of the complexity of long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1117464}, pmid = {37153597}, issn = {1664-3224}, support = {MC_PC_16022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Public Health ; Risk Factors ; }, abstract = {Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2) infection, or Long COVID, is a prevailing second pandemic with nearly 100 million affected individuals globally and counting. We propose a visual description of the complexity of Long COVID and its pathogenesis that can be used by researchers, clinicians, and public health officials to guide the global effort toward an improved understanding of Long COVID and the eventual mechanism-based provision of care to afflicted patients. The proposed visualization or framework for Long COVID should be an evidence-based, dynamic, modular, and systems-level approach to the condition. Furthermore, with further research such a framework could establish the strength of the relationships between pre-existing conditions (or risk factors), biological mechanisms, and resulting clinical phenotypes and outcomes of Long COVID. Notwithstanding the significant contribution that disparities in access to care and social determinants of health have on outcomes and disease course of long COVID, our model focuses primarily on biological mechanisms. Accordingly, the proposed visualization sets out to guide scientific, clinical, and public health efforts to better understand and abrogate the health burden imposed by long COVID.}, } @article {pmid37153089, year = {2023}, author = {Angarita-Fonseca, A and Torres-Castro, R and Benavides-Cordoba, V and Chero, S and Morales-Satán, M and Hernández-López, B and Salazar-Pérez, R and Larrateguy, S and Sanchez-Ramirez, DC}, title = {Exploring long COVID condition in Latin America: Its impact on patients' activities and associated healthcare use.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1168628}, pmid = {37153089}, issn = {2296-858X}, abstract = {BACKGROUND: Studies exploring long COVID condition (LCC) in low- and middle-income countries are scarce. Further characterization of LCC patients experiencing activity limitations and their associated healthcare use is needed. This study aimed to describe LCC patients' characteristics, its impact on activities, and associated healthcare use in Latin America (LATAM).

PARTICIPANTS: Individuals who (cared for someone or) had COVID-19 and could read, write, and comprehend Spanish and lived in a LATAM country were invited to complete a virtual survey. Sociodemographic characteristics, COVID-19 and LCC symptoms, activity limitations, and healthcare use.

RESULTS: Data from 2,466 people from 16 countries in LATAM were analyzed (females = 65.9%; mean age of 39.5 ± 53.3 years). 1,178 (48%) of the respondents had LCC symptoms (≥3 months). These were more likely to have COVID-19 earlier in the pandemic, were older, had no COVID vaccines, had more comorbidities, needed supplementary oxygen, and reported significantly more COVID-19 symptoms during the infectious period. 33% of the respondents visited a primary care provider, 13% went to the emergency department, 5% were hospitalized, 21% visited a specialist, and 32% consulted ≥1 therapist for LCC symptoms mainly extreme fatigue, sleep difficulties, headaches, muscle or joint pain, and shortness of breath with activity. The most consulted therapists were respiratory therapists (15%) and psychologists (14%), followed by physical therapists (13%), occupational therapists (3%), and speech pathologists (1%). One-third of LCC respondents decreased their regular activities (e.g., work, school) and 8% needed help with activities of daily living (ADLs). LCC respondents who reduced their activities reported more difficulty sleeping, chest pain with activity, depression, and problems with concentration, thinking, and memory, while those who needed help with ADLs were more likely to have difficulty walking, and shortness of breath at rest. Approximately 60% of respondents who experienced activity limitations sought a specialist and 50% consulted therapists.

CONCLUSIONS AND RELEVANCE: Results supported previous findings in terms of the LCC demographics, and provided insight into LCC impact on patients' activities and healthcare services used in LATAM. This information is valuable to inform service planning and resource allocation in alignment with the needs of this population.}, } @article {pmid37152805, year = {2023}, author = {Goda, GS and Soltas, EJ}, title = {The impacts of Covid-19 absences on workers.}, journal = {Journal of public economics}, volume = {222}, number = {}, pages = {104889}, pmid = {37152805}, issn = {0047-2727}, support = {P30 AG012810/AG/NIA NIH HHS/United States ; }, abstract = {We show that Covid-19 illnesses and related work absences persistently reduce labor supply. Using an event study, we estimate that workers with week-long Covid-19 absences are 7 percentage points less likely to be in the labor force one year later compared to otherwise-similar workers who do not miss a week of work for health reasons. Our estimates suggest Covid-19 absences have reduced the U.S. labor force by approximately 500,000 people (0.2 percent of adults) and imply an average labor supply loss per Covid-19 absence equivalent to $9,000 in forgone earnings, about 90 percent of which reflects losses beyond the initial absence week.}, } @article {pmid37151592, year = {2023}, author = {Giuliano, M and Tiple, D and Agostoni, P and Armocida, B and Biardi, L and Bonfigli, AR and Campana, A and Ciardi, M and Di Marco, F and Floridia, M and Gnerre, P and Grassi, T and Grattagliano, I and Kruger, P and Leonardi, M and Liguori, R and Pagani, E and Perger, E and Pricci, F and Ruggeri, M and Silenzi, A and Spannella, F and Tascini, C and Teté, G and Tosato, M and Vecchi, S and Villa, M and Onder, G}, title = {Italian good practice recommendations on management of persons with Long-COVID.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1122141}, pmid = {37151592}, issn = {2296-2565}, mesh = {Humans ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/therapy ; SARS-CoV-2 ; *Geriatrics ; Health Services Accessibility ; }, abstract = {A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient's needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients.}, } @article {pmid37150660, year = {2023}, author = {Rossi Neto, JM and Rossi, RM and Wolf, PJW and De Mello, VB and Dantas, DC and Santos, CCD and Finger, MA}, title = {Long Covid as an Indication for Heart Transplantation and Its Characteristics.}, journal = {Transplantation proceedings}, volume = {55}, number = {8}, pages = {1870-1872}, pmid = {37150660}, issn = {1873-2623}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Heart Transplantation/adverse effects ; *Heart Failure/etiology/surgery/drug therapy ; }, abstract = {BACKGROUND: The post-acute cardiovascular manifestations of COVID-19, known as long COVID, have yet to be comprehensively characterized. There is also an increased risk of heart failure in individuals without cardiovascular disease before SARS-CoV-2 infection. The literature lacks information regarding the characteristics of patients with long COVID who developed advanced heart failure refractory to guideline-directed medical therapy.

METHODS: We describe the characteristics of patients with long COVID (LC) who were listed for heart transplantation. The study population comprised 45 patients listed for heart transplantation, divided into 2 groups: patients with etiologies other than LC (n = 41) and patients with LC (n = 4) between January 2020 and March 2022. The endpoint of this study was the description of the characteristics of each group.

RESULTS: The average duration of hospitalization after the acute infectious episode with SARS-CoV-2 was 150 ± 113 days, and all patients were hospitalized in New York Heart Association class IV. All LC patients were oligosymptomatic in the initial infection, did not require hospitalization in the acute phase, had a lower ejection fraction, used more intra-aortic balloon pumps, had lower pulmonary vascular resistance, and fewer comorbidities compared with other etiologies, suggesting a clinical feature compatible with low cardiac output rather than congestion.

CONCLUSIONS: This study is an early investigation of patients listed for heart transplantation due to a complex syndrome of COVID-19. These preliminary findings warrant further large-scale investigation.}, } @article {pmid37150350, year = {2023}, author = {Kuodi, P and Gorelik, Y and Gausi, B and Bernstine, T and Edelstein, M}, title = {Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {134}, number = {}, pages = {1-7}, doi = {10.1016/j.ijid.2023.05.003}, pmid = {37150350}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Public Health ; }, abstract = {OBJECTIVES: The objective of this study was to characterize post-COVID condition symptoms and symptom clusters, their duration, and prevalence.

METHODS: We conducted a systematic review and random-effects meta-analysis of studies reporting post-COVID-19 symptoms and clusters, respectively. We searched MEDLINE (via PubMed), Scopus, Web of Science, Science Direct, Google Scholar, EBSCOhost, EMBASE, PsycINFO, Cochrane Library, and Mednar for literature reporting on the post-COVID condition up to August 2022.

RESULTS: In the 76 included studies, we found that although most symptoms were reported less frequently 7-12 months after infection compared to earlier, over 20% of patients reported at least one post-COVID condition-compatible symptom. In the seven studies reporting post-COVID symptom clusters, neurological clustering was consistently identified, followed by cardiorespiratory and systemic/inflammatory.

CONCLUSION: Post-COVID symptom clustering provides direction for research into the etiology, diagnosis, and management of post-COVID conditions. Studies reporting post-COVID symptom clusters remain rare due to the focus on individual symptom reporting. Studies on post-COVID symptom clusters should replace individual symptom reporting to accelerate our understanding of this emerging public health issue.}, } @article {pmid37147609, year = {2023}, author = {Ogaz, D and Allen, H and Reid, D and Brown, JRG and Howarth, AR and Pulford, CV and Mercer, CH and Saunders, J and Hughes, G and Mohammed, H}, title = {COVID-19 infection and vaccination uptake in men and gender-diverse people who have sex with men in the UK: analyses of a large, online community cross-sectional survey (RiiSH-COVID) undertaken November-December 2021.}, journal = {BMC public health}, volume = {23}, number = {1}, pages = {829}, pmid = {37147609}, issn = {1471-2458}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Female ; Humans ; Male ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Cross-Sectional Studies ; England ; Homosexuality, Male ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Sexual and Gender Minorities ; Vaccination ; Adolescent ; Young Adult ; }, abstract = {BACKGROUND: Men and gender-diverse people who have sex with men are disproportionately affected by health conditions associated with increased risk of severe illness due to COVID-19 infection.

METHODS: An online cross-sectional survey of men and gender-diverse people who have sex with men in the UK recruited via social networking and dating applications from 22 November-12 December 2021. Eligible participants included self-identifying men, transgender women, or gender-diverse individuals assigned male at birth (AMAB), aged ≥ 16, who were UK residents, and self-reported having had sex with an individual AMAB in the last year. We calculated self-reported COVID-19 test-positivity, proportion reporting long COVID, and COVID-19 vaccination uptake anytime from pandemic start to survey completion (November/December 2021). Logistic regression was used to assess sociodemographic, clinical, and behavioural characteristics associated with SARS-CoV-2 (COVID-19) test positivity and complete vaccination (≥ 2 vaccine doses).

RESULTS: Among 1,039 participants (88.1% white, median age 41 years [interquartile range: 31-51]), 18.6% (95% CI: 16.3%-21.1%) reported COVID-19 test positivity, 8.3% (95% CI: 6.7%-10.1%) long COVID, and 94.5% (95% CI: 93.3%-96.1%) complete COVID-19 vaccination through late 2021. In multivariable models, COVID-19 test positivity was associated with UK country of residence (aOR: 2.22 [95% CI: 1.26-3.92], England vs outside England) and employment (aOR: 1.55 [95% CI: 1.01-2.38], current employment vs not employed). Complete COVID-19 vaccination was associated with age (aOR: 1.04 [95% CI: 1.01-1.06], per increasing year), gender (aOR: 0.26 [95% CI: 0.09-0.72], gender minority vs cisgender), education (aOR: 2.11 [95% CI: 1.12-3.98], degree-level or higher vs below degree-level), employment (aOR: 2.07 [95% CI: 1.08-3.94], current employment vs not employed), relationship status (aOR: 0.50 [95% CI: 0.25-1.00], single vs in a relationship), COVID-19 infection history (aOR: 0.47 [95% CI: 0.25-0.88], test positivity or self-perceived infection vs no history), known HPV vaccination (aOR: 3.32 [95% CI: 1.43-7.75]), and low self-worth (aOR: 0.29 [95% CI: 0.15-0.54]).

CONCLUSIONS: In this community sample, COVID-19 vaccine uptake was high overall, though lower among younger age-groups, gender minorities, and those with poorer well-being. Efforts are needed to limit COVID-19 related exacerbation of health inequalities in groups who already experience a greater burden of poor health relative to other men who have sex with men.}, } @article {pmid37147589, year = {2023}, author = {Prato, A and Salerno, AM and Saia, F and Maugeri, N and Zanini, A and Scerbo, M and Barone, R and Rizzo, R}, title = {Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS‑CoV‑2 infection: a short-term follow-up assessment.}, journal = {BMC pediatrics}, volume = {23}, number = {1}, pages = {222}, pmid = {37147589}, issn = {1471-2431}, mesh = {Adolescent ; Humans ; Child ; *Tics/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Communicable Disease Control ; *Tic Disorders/complications/psychology ; *Tourette Syndrome/complications/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3-1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID.

OBJECTIVES: Considering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS.

METHODS: We conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children-present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL).

RESULTS: Among the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it.

CONCLUSIONS: SARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.}, } @article {pmid37147332, year = {2023}, author = {Wu, S and Huang, Z and Grant-Muller, S and Gu, D and Yang, L}, title = {Modelling the reopen strategy from dynamic zero-COVID in China considering the sequela and reinfection.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {7343}, pmid = {37147332}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Reinfection ; China/epidemiology ; }, abstract = {Although the dynamic zero-COVID policy has effectively controlled virus spread in China, China has to face challenges in balancing social-economic burdens, vaccine protection, and the management of long COVID symptoms. This study proposed a fine-grained agent-based model to simulate various strategies for transitioning from a dynamic zero-COVID policy with a case study in Shenzhen. The results indicate that a gradual transition, maintaining some restrictions, can mitigate infection outbreaks. However, the severity and duration of epidemics vary based on the strictness of the measures. In contrast, a more direct transition to reopening may lead to rapid herd immunity but necessitate preparedness for potential sequelae and reinfections. Policymakers should assess healthcare capacity for severe cases and potential long-COVID symptoms and determine the most suitable approach tailored to local conditions.}, } @article {pmid37145596, year = {2023}, author = {Liu, TC and Yoo, SM and Sim, MS and Motwani, Y and Viswanathan, N and Wenger, NS}, title = {Perceived Cognitive Deficits in Patients With Symptomatic SARS-CoV-2 and Their Association With Post-COVID-19 Condition.}, journal = {JAMA network open}, volume = {6}, number = {5}, pages = {e2311974}, pmid = {37145596}, issn = {2574-3805}, support = {UL1 TR001881/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Male ; Humans ; Middle Aged ; *SARS-CoV-2 ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Cognition ; }, abstract = {IMPORTANCE: Neuropsychiatric symptoms are common in acute SARS-CoV-2 infection and in post-COVID-19 condition (PCC; colloquially known as long COVID), but the association between early presenting neuropsychiatric symptoms and PCC is unknown.

OBJECTIVE: To describe the characteristics of patients with perceived cognitive deficits within the first 4 weeks of SARS-CoV-2 infection and the association of those deficits with PCC symptoms.

This prospective cohort study was conducted from April 2020 to February 2021, with follow-up of 60 to 90 days. The cohort consisted of adults enrolled in the University of California, Los Angeles, SARS-CoV-2 Ambulatory Program who had a laboratory-confirmed symptomatic SARS-CoV-2 infection and were either hospitalized in a University of California, Los Angeles, hospital or one of 20 local health care facilities, or were outpatients referred by a primary care clinician. Data analysis was performed from March 2022 to February 2023.

EXPOSURE: Laboratory-confirmed SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: Patients responded to surveys that included questions about perceived cognitive deficits modified from the Perceived Deficits Questionnaire, Fifth Edition, (ie, trouble being organized, trouble concentrating, and forgetfulness) and symptoms of PCC at 30, 60, and 90 days after hospital discharge or initial laboratory-confirmed infection of SARS-CoV-2. Perceived cognitive deficits were scored on a scale from 0 to 4. Development of PCC was determined by patient self-report of persistent symptoms 60 or 90 days after initial SARS-CoV-2 infection or hospital discharge.

RESULTS: Of 1296 patients enrolled in the program, 766 (59.1%) (mean [SD] age, 60.0 [16.7] years; 399 men [52.1%]; 317 Hispanic/Latinx patients [41.4%]) completed the perceived cognitive deficit items at 30 days after hospital discharge or outpatient diagnosis. Of the 766 patients, 276 (36.1%) perceived a cognitive deficit, with 164 (21.4%) having a mean score of greater than 0 to 1.5 and 112 patients (14.6 %) having a mean score greater than 1.5. Prior cognitive difficulties (odds ratio [OR], 1.46; 95% CI, 1.16-1.83) and diagnosis of depressive disorder (OR, 1.51; 95% CI, 1.23-1.86) were associated with report of a perceived cognitive deficit. Patients reporting perceived cognitive deficits in the first 4 weeks of SARS-CoV-2 infection were more likely to report symptoms of PCC than those without perceived cognitive deficits (118 of 276 patients [42.8%] vs 105 of 490 patients [21.4%]; χ21, 38.9; P < .001). Adjusting for demographic and clinical factors, perceived cognitive deficits in the first 4 weeks of SARS-CoV-2 were associated with PCC symptoms (patients with a cognitive deficit score of >0 to 1.5: OR, 2.42; 95% CI, 1.62-3.60; patients with cognitive deficit score >1.5: OR, 2.97; 95% CI, 1.86-4.75) compared to patients who reported no perceived cognitive deficits.

CONCLUSIONS AND RELEVANCE: These findings suggest that patient-reported perceived cognitive deficits in the first 4 weeks of SARS-CoV-2 infection are associated with PCC symptoms and that there may be an affective component to PCC in some patients. The underlying reasons for PCC merit additional exploration.}, } @article {pmid37145350, year = {2023}, author = {Moukayed, M}, title = {A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.}, journal = {Current nutrition reports}, volume = {12}, number = {2}, pages = {215-223}, pmid = {37145350}, issn = {2161-3311}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Cholecalciferol ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19.

RECENT FINDINGS: Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.}, } @article {pmid37144614, year = {2023}, author = {Peluso, MJ and Antar, AAR}, title = {Long COVID in people living with HIV.}, journal = {Current opinion in HIV and AIDS}, volume = {18}, number = {3}, pages = {126-134}, pmid = {37144614}, issn = {1746-6318}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 AI158013/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; *HIV Infections/complications ; Awareness ; }, abstract = {PURPOSE OF REVIEW: It is now recognized that SARS-CoV-2 infection can have a long-term impact on health. This review summarizes the current state of knowledge regarding Long COVID in people living with HIV (PLWH).

RECENT FINDINGS: PLWH may be at elevated risk of experiencing Long COVID. Although the mechanisms contributing to Long COVID are incompletely understood, there are several demographic and clinical factors that might make PLWH vulnerable to developing Long COVID.

SUMMARY: PLWH should be aware that new or worsening symptoms following SARS-CoV-2 infection might represent Long COVID. HIV providers should be aware of this clinical entity and be mindful that their patients recovering from SARS-CoV-2 infection may be at higher risk.}, } @article {pmid37142087, year = {2023}, author = {Queiroz-Junior, CM and Santos, ACPM and Gonçalves, MR and Brito, CB and Barrioni, B and Almeida, PJ and Gonçalves-Pereira, MH and Silva, T and Oliveira, SR and Pereira, MM and Santiago, HC and Teixeira, MM and Costa, VV}, title = {Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice.}, journal = {Life sciences}, volume = {324}, number = {}, pages = {121750}, pmid = {37142087}, issn = {1879-0631}, mesh = {Animals ; Humans ; Mice ; *Bone Resorption/metabolism ; Cell Differentiation ; *COVID-19/metabolism ; Osteoblasts ; Osteoclasts/metabolism ; Osteoprotegerin/metabolism ; Pandemics ; Phenotype ; Post-Acute COVID-19 Syndrome ; RANK Ligand/metabolism ; SARS-CoV-2/metabolism ; Murine hepatitis virus/metabolism/pathogenicity ; Coronavirus Infections/genetics/metabolism ; }, abstract = {AIMS: Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism.

MAIN METHODS: We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3).

KEY FINDINGS: Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3[+] cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55[-/-] mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts.

SIGNIFICANCE: Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.}, } @article {pmid37141260, year = {2023}, author = {Gonçalo Silva, GA and Nogueira, IDB and da Silva Chiappa, GR and Nogueira, PAMS}, title = {Efficacy of home-based inspiratory muscle training in patients post-covid-19: Protocol for a randomized clinical trial.}, journal = {PloS one}, volume = {18}, number = {5}, pages = {e0279310}, pmid = {37141260}, issn = {1932-6203}, mesh = {Humans ; *Quality of Life ; Hand Strength ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Breathing Exercises/methods ; Diaphragm ; Respiratory Muscles ; Dyspnea/therapy ; Muscle Strength/physiology ; Exercise Tolerance/physiology ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Current evidence suggests the emergence of a novel syndrome (long COVID syndrome) due to sequels and persistent COVID-19 symptoms. Respiratory muscle training improves respiratory muscle strength, exercise capacity, diaphragm thickness, and dyspnea, especially in patients with decreased respiratory muscle strength. This study aims to evaluate the effectiveness of a protocol for home-based inspiratory muscle training to improve respiratory muscle strength, dyspnea, and quality of life of patients post-COVID-19.

METHODS AND ANALYSES: This randomized, controlled, double-blind clinical trial will be conducted at the Instituto de Medicina Tropical of Universidade Federal do Rio Grande do Norte (Brazil). Sample size will be determined using maximal inspiratory pressure after a pilot study with five patients per group (total of 10 patients). Patients included in the study will be evaluated in three moments: pre-training (initial), post-training (three weeks), and retention (24 weeks). The sample will be randomized in two groups: active (IMT using 30% of IMT and load increase of 10% of initial IMT every week. Patients will perform 30 repetitions, twice a day (morning and afternoon), for seven consecutive days, and six weeks) and SHAM (IMT without load). The following measurements will be assessed: anthropometry, respiratory muscle strength, pulmonary volume and capacity, dyspnea, perception of effort and lower limb fatigue, handgrip strength, functional capacity, anxiety, depression, and functional status. After initial evaluation, all patients will receive a POWERbreathe® (POWERbreathe®, HaB Ltd, Southam, UK) device to perform the training. Normality will be verified using Shapiro-Wilk or Kolmogorov-Smirnov, according to the number of patients included. Variables presenting nonparametric distribution will be compared using Wilcoxon (intragroup analysis) and Mann-Whitney test (intergroup analysis), whereas repeated measures two-way ANOVA will be performed in case of parametric distribution. Dunn's post hoc test will be used to identify significant differences in the two-way ANOVA test.

PRIMARY OUTCOMES: Respiratory muscle strength, dyspnea, and quality of life of post-COVID-19 patients.

SECOND OUTCOMES: Pulmonary function, dyspnea, exercise tolerance, handgrip strength, anxiety, depression, and functional status.

TRIAL REGISTRATION: Trial register number NCT05077241.}, } @article {pmid37141019, year = {2023}, author = {Winter, D and Braw, Y}, title = {Effects of diagnosis threat on cognitive complaints after COVID-19.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {42}, number = {5}, pages = {335-342}, doi = {10.1037/hea0001286}, pmid = {37141019}, issn = {1930-7810}, mesh = {Humans ; *COVID-19 ; *Cognitive Dysfunction/diagnosis/etiology ; Forecasting ; Cognition ; Fatigue/diagnosis/epidemiology/etiology ; COVID-19 Testing ; }, abstract = {OBJECTIVE: The term "long-COVID" refers to the persistence of neurological symptoms after being ill with COVID-19 (e.g., headaches, fatigue, and attentional impairment). Providing information about long-COVID (i.e., "diagnosis threat") increased subjective cognitive complaints among recovered COVID-19 patients compared with those exposed to neutral information (Winter & Braw, 2022). Notably, this effect was particularly prominent among more suggestible participants. Our aim in the current study was to validate these initial findings and to explore the impact of additional variables (e.g., suggestibility).

METHOD: Recovered patients (n = 270) and controls (n = 290) reported daily cognitive failures after being randomly assigned to either a diagnosis threat (exposure to an article providing information regarding long-COVID) or a control condition.

RESULTS: Recovered patients, but not controls, reported more cognitive failures in the diagnosis threat condition compared with the control condition. Diagnosis threat added significantly to the prediction of cognitive complaints based on relevant demographic variables and suggestibility. Diagnosis threat and suggestibility interacted (i.e., suggestible individuals were particularly vulnerable to the impact of a diagnosis threat).

CONCLUSIONS: Diagnosis threat may contribute to the persistence of complaints regarding cognitive impairment among recovered COVID-19 patients. Suggestibility may be an underlying mechanism that increases the impact of diagnosis threat. Other factors, such as vaccination status, may be at play though we are only at the initial stages of research concerning their impact. These may be the focus of future research, aiding in identifying risk factors for experiencing COVID-19 symptoms past the resolution of its acute phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid37140960, year = {2023}, author = {Chen, B and Julg, B and Mohandas, S and Bradfute, SB and , }, title = {Viral persistence, reactivation, and mechanisms of long COVID.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37140960}, issn = {2050-084X}, support = {K08 HL141623/HL/NHLBI NIH HHS/United States ; R01 AI162223/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {United States ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; RNA, Viral ; SARS-CoV-2 ; Disease Progression ; }, abstract = {The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse. In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.}, } @article {pmid37140186, year = {2024}, author = {Bergmans, RS and Chambers-Peeple, K and Yu, C and Xiao, LZ and Wegryn-Jones, R and Martin, A and Dell'Imperio, S and Aboul-Hassan, D and Williams, DA and Clauw, DJ and DeJonckheere, M}, title = {'I'm still here, I'm alive and breathing': The experience of Black Americans with long COVID.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {162-177}, pmid = {37140186}, issn = {1365-2702}, support = {T32 AR007080/AR/NIAMS NIH HHS/United States ; T32-AR07080/AR/NIAMS NIH HHS/United States ; T32-AR07080/AR/NIAMS NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Black or African American ; *COVID-19 ; *Post-Acute COVID-19 Syndrome/epidemiology ; Qualitative Research ; Quality of Life ; }, abstract = {AIMS AND OBJECTIVES: In this study, we aimed to characterize the impact of long COVID on quality of life and approaches to symptom management among Black American adults.

BACKGROUND: As a novel condition, qualitative evidence concerning long COVID symptoms and their impact on quality of life can inform the refinement of diagnostic criteria and care plans. However, the underrepresentation of Black Americans in long COVID research is a barrier to achieving equitable care for all long COVID patients.

DESIGN: We employed an interpretive description study design.

METHODS: We recruited a convenience sample of 15 Black American adults with long COVID. We analysed the anonymized transcripts from race-concordant, semi-structured interviews using an inductive, thematic analysis approach. We followed the SRQR reporting guidelines.

RESULTS: We identified four themes: (1) The impact of long COVID symptoms on personal identity and pre-existing conditions; (2) Self-management strategies for long COVID symptoms; (3) Social determinants of health and symptom management; and (4) Effects on interpersonal relationships.

CONCLUSION: Findings demonstrate the comprehensive ramifications of long COVID on the lives of Black American adults. Results also articulate how pre-existing conditions, social risk factors, distrust due to systemic racism, and the nature of interpersonal relationships can complicate symptom management.

Care approaches that support access to and implementation of integrative therapies may be best suited to meet the needs of long COVID patients. Clinicians should also prioritize eliminating patient exposure to discrimination, implicit bias, and microaggressions. This is of particular concern for long COVID patients who have symptoms that are difficult to objectively quantify, such as pain and fatigue.

While patient perspectives and experiences were the focus of this study, patients were not involved with the design or conduct of the study, data analysis or interpretation, or writing the manuscript.}, } @article {pmid37138871, year = {2023}, author = {Queiroz, MAF and Santiago, AM and Brito, WRDS and Pereira, KAS and de Brito, WB and Torres, MKDS and Lopes, JDC and Dos Santos, EF and da Costa, FP and de Sarges, KML and Cantanhede, MHD and de Brito, MTFM and da Silva, ALS and Leite, MM and Viana, MNDSA and Rodrigues, FBB and da Silva, R and Viana, GMR and Chaves, TDSS and Veríssimo, AOL and Carvalho, MDS and Henriques, DF and Dos Santos, CP and Nunes, JAL and Costa, IB and Amoras, EDSG and Lima, SS and Cayres-Vallinoto, IMV and Brasil-Costa, I and Quaresma, JAS and Falcão, LFM and Dos Santos, EJM and Vallinoto, ACR}, title = {Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1151058}, pmid = {37138871}, issn = {1664-3224}, mesh = {Humans ; Tumor Necrosis Factor-alpha/genetics ; Interleukin-6/genetics ; Cytokines/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; Polymorphism, Genetic ; *Mannose-Binding Lectin/genetics ; }, abstract = {INTRODUCTION: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.

METHODS: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.

RESULTS: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.

DISCUSSION: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.}, } @article {pmid37137489, year = {2024}, author = {Ladlow, P and Barker-Davies, R and Hill, O and Conway, D and O'Sullivan, O}, title = {Use of symptom-guided physical activity and exercise rehabilitation for COVID-19 and other postviral conditions.}, journal = {BMJ military health}, volume = {170}, number = {6}, pages = {510-515}, doi = {10.1136/military-2023-002399}, pmid = {37137489}, issn = {2633-3775}, mesh = {Humans ; *COVID-19/rehabilitation ; *Exercise Therapy/methods ; *Exercise/physiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; United Kingdom ; }, abstract = {There are many similarities in symptoms between postviral conditions, including clinical features such as fatigue, reduced daily activity and postexertional symptom exacerbation. Unfavourable responses to exercise have influenced the wider debate on how to reintegrate physical activity (PA) and exercise while simultaneously managing symptoms during recovery from post-COVID-19 syndrome (or Long COVID). This has resulted in inconsistent advice from the scientific and clinical rehabilitation community on how and when to resume PA and exercise following COVID-19 illness. This article provides commentary on the following topics: (1) controversies surrounding graded exercise therapy as a treatment modality for post-COVID-19 rehabilitation; (2) evidence supporting PA promotion, resistance exercise and cardiorespiratory fitness for population health, and the consequences of physical inactivity in patients with complex rehabilitation needs; (3) population-based challenges for UK Defence Rehabilitation practitioners for the management of postviral conditions; and (4) 'symptom guided PA and exercise rehabilitation' as an appropriate treatment option for managing individuals with multifaceted medical needs.}, } @article {pmid37137186, year = {2023}, author = {González-Hermosillo G, JA and Galarza, EJ and Fermín, OV and González, JMN and Tostado, LMFÁ and Lozano, MAE and Rabasa, CR and Martínez Alvarado, MDR}, title = {Exaggerated blood pressure elevation in response to orthostatic challenge, a post-acute sequelae of SARS-CoV-2 infection (PASC) after hospitalization.}, journal = {Autonomic neuroscience : basic & clinical}, volume = {247}, number = {}, pages = {103094}, pmid = {37137186}, issn = {1872-7484}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; Blood Pressure ; *Autonomic Nervous System Diseases ; Hospitalization ; *Hypertension ; Disease Progression ; }, abstract = {OBJECTIVE: Post-acute sequelae of SARS-COV-2 (PASC) are emerging as a major health challenge. Orthostatic intolerance secondary to autonomic failure has been found in PASC patients. This study investigated the effect of COVID-19 after recovery on blood pressure (BP) during the orthostatic challenge.

RESEARCH DESIGN AND METHODS: Thirty-one out of 45 patients hospitalized due to COVID-19-related pneumonia that developed PASC and did not have hypertension at discharge were studied. They underwent a head-up tilt test (HUTT) at 10.8 ± 1.9 months from discharge. All met the PASC clinical criteria, and an alternative diagnosis did not explain the symptoms. This population was compared with 32 historical asymptomatic healthy controls.

RESULTS: Exaggerated orthostatic blood pressure response (EOPR)/orthostatic hypertension (OHT) was detected in 8 out of 23 (34.7 %) patients, representing a significantly increased prevalence (7.67-fold increase p = 0.009) compared to 2 out of 32 (6.4 %) asymptomatic healthy controls matched by age, who underwent HUTT and were not infected with SARS-CoV-2.

CONCLUSIONS: This prospective evaluation in patients with PASC revealed abnormal blood pressure rise during the orthostatic challenge, suggesting of autonomic dysfunction in a third of the studied subjects. Our findings support the hypothesis that EOPR/OHT may be a phenotype of neurogenic hypertension. Hypertension in PASC patients may adversely affect the cardiovascular burden in the world.}, } @article {pmid37133827, year = {2023}, author = {Landhuis, EW}, title = {How Primary Care Physicians Can Recognize and Treat Long COVID.}, journal = {JAMA}, volume = {329}, number = {20}, pages = {1727-1729}, doi = {10.1001/jama.2023.6604}, pmid = {37133827}, issn = {1538-3598}, mesh = {Humans ; *COVID-19/complications/diagnosis/therapy ; *Physicians, Primary Care ; *Post-Acute COVID-19 Syndrome/diagnosis/therapy ; SARS-CoV-2 ; }, } @article {pmid37133220, year = {2023}, author = {Goussard, P and Venkatakrishna, S and Frigati, L and Janson, J and Schubert, P and Verster, J and Gie, AG and Myburgh, C and Parker, N and Du Plooy, E and Rhode, D and Bekker, C and Andronikou, S and Rabie, H and van der Zalm, MM}, title = {Chronic lung disease in children due to SARS-CoV-2 pneumonia: Case series.}, journal = {Pediatric pulmonology}, volume = {58}, number = {7}, pages = {2111-2123}, pmid = {37133220}, issn = {1099-0496}, support = {K43 TW011028/TW/FIC NIH HHS/United States ; }, mesh = {Infant ; Adult ; Adolescent ; Humans ; Child ; *SARS-CoV-2 ; *COVID-19/complications ; Lung/diagnostic imaging ; Polymerase Chain Reaction ; Hospitalization ; }, abstract = {The reported prevalence of chronic lung disease (CLD) due to coronavirus 2 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2)]) pneumonia with the severe acute respiratory syndrome in children is unknown and rarely reported in English literature. In contrast to most other respiratory viruses, children generally have less severe symptoms when infected with SARS-CoV-2. Although only a minority of children with SARS-CoV-2 infection require hospitalization, severe cases have been reported. More severe SARS-CoV-2 respiratory disease in infants has been reported in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe our experience of five cases of CLD in children due to SARS-CoV-2 collected between April 2020 and August 2022. We included children who had a history of a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test or a positive antibody test in the serum. Three patterns of CLD related to SARS-CoV-2 were identified: (1) CLD in infants postventilation for severe pneumonia (n = 3); (2) small airway disease with bronchiolitis obliterans picture (n = 1) and (3) adolescent with adult-like post-SARS-CoV-2 disease (n = 1). Chest computerized tomography scans showed airspace disease and ground-glass opacities involving both lungs with the development of coarse interstitial markings seen in four patients, reflecting the long-term fibrotic consequences of diffuse alveolar damage that occur in children post-SARS-CoV-2 infection. Children with SARS-CoV-2 infection mostly have mild symptoms with little to no long-term sequelae, but the severe long-term respiratory disease can develop.}, } @article {pmid37132023, year = {2023}, author = {Prashar, J}, title = {Long Covid: conceptualizing the challenges for public health.}, journal = {Journal of public health (Oxford, England)}, volume = {45}, number = {3}, pages = {771-779}, pmid = {37132023}, issn = {1741-3850}, mesh = {Humans ; *Public Health ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Health Status Disparities ; Delivery of Health Care ; }, abstract = {BACKGROUND: Long Covid has caused significant disruption to public services, economies and population health worldwide, but no single public health approach has proven effective in its management. This essay was the winning entry for the Faculty of Public Health's Sir John Brotherston Prize 2022.

METHODS: In this essay, I synthesize existing literature on public health policy in long Covid, and discuss the challenges and opportunities posed by long Covid for the public health profession. The utility of specialist clinics and community care, in the UK and internationally, is examined, as well as key outstanding issues relating to evidence generation, health inequality and defining long Covid. I then use this information to inform a simple conceptual model.

RESULTS: The generated conceptual model integrates community- and population-level interventions; key areas of identified policy need at both levels include ensuring equitable access to long Covid care, developing screening programmes for high-risk populations, co-production of research and clinical services with patients, and using interventions to generate evidence.

CONCLUSIONS: Significant challenges remain in the management of long Covid from a public health policy perspective. Multidisciplinary community-level and population-level interventions should be employed with a view to achieving an equitable and scalable model of care.}, } @article {pmid37131862, year = {2023}, author = {Yu, Z and Ekström, S and Bellander, T and Ljungman, P and Pershagen, G and Eneroth, K and Kull, I and Bergström, A and Georgelis, A and Stafoggia, M and Gruzieva, O and Melén, E and , }, title = {Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden.}, journal = {The Lancet regional health. Europe}, volume = {28}, number = {}, pages = {100608}, pmid = {37131862}, issn = {2666-7762}, abstract = {BACKGROUND: Post COVID-19 conditions, also known as long COVID, are of public health concern, but little is known about their underlying risk factors. We aimed to investigate associations of air pollution exposure with long COVID among Swedish young adults.

METHODS: We used data from the BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology [in Swedish]) cohort. From October 2021 to February 2022 participants answered a web-questionnaire focusing on persistent symptoms following acute SARS-CoV-2 infection. Long COVID was defined as symptoms after confirmed infection with SARS-CoV-2 lasting for two months or longer. Ambient air pollution levels (particulate matter ≤2.5 μm [PM2.5], ≤10 μm [PM10], black carbon [BC] and nitrogen oxides [NOx]) at individual-level addresses were estimated using dispersion modelling.

FINDINGS: A total of 753 participants with SARS-CoV-2 infection were included of whom 116 (15.4%) reported having long COVID. The most common symptoms were altered smell/taste (n = 80, 10.6%), dyspnea (n = 36, 4.8%) and fatigue (n = 34, 4.5%). Median annual PM2.5 exposure in 2019 (pre-pandemic) was 6.39 (interquartile range [IQR] 6.06-6.71) μg/m[3]. Adjusted Odds Ratios (95% confidence intervals) of PM2.5 per IQR increase were 1.28 (1.02-1.60) for long COVID, 1.65 (1.09-2.50) for dyspnea symptoms and 1.29 (0.97-1.70) for altered smell/taste. Positive associations were found for the other air pollutants and remained consistent across sensitivity analyses. Associations tended to be stronger among participants with asthma, and those having had COVID during 2020 (versus 2021).

INTERPRETATION: Ambient long-term PM2.5 exposure may affect the risk of long COVID in young adults, supporting efforts for continuously improving air quality.

FUNDING: The study received funding from the Swedish Research Council (grant no. 2020-01886, 2022-06340), the Swedish Research Council for Health, Working life and Welfare (FORTE grant no. 2017-01146), the Swedish Heart-Lung Foundation, Karolinska Institute (no. 2022-01807) and Region Stockholm (ALF project for cohort and database maintenance).}, } @article {pmid37131860, year = {2023}, author = {Yang, C and Tebbutt, SJ}, title = {Long COVID: the next public health crisis is already on its way.}, journal = {The Lancet regional health. Europe}, volume = {28}, number = {}, pages = {100612}, pmid = {37131860}, issn = {2666-7762}, } @article {pmid37131536, year = {2023}, author = {Hua, MJ and Gonakoti, S and Shariff, R and Corpuz, C and Acosta, RAH and Chang, H and Asemota, I and Gobbi, E and Rezai, K}, title = {Prevalence and Characteristics of Long COVID 7-12 Months After Hospitalization Among Patients From an Urban Safety-Net Hospital: A Pilot Study.}, journal = {AJPM focus}, volume = {2}, number = {3}, pages = {100091}, pmid = {37131536}, issn = {2773-0654}, abstract = {INTRODUCTION: Little is known about the burden of long COVID among Black and Hispanic patients in the U.S. We surveyed adult patients hospitalized for COVID-19 at John H. Roger, Jr. Hospital of Cook County, a safety-net hospital predominantly serving Black and Hispanic patients in Chicago, for persistent symptoms after hospitalization to assess prevalence and identify risk factors.

METHODS: Cross-sectional data were obtained over 6 months after discharge from patients hospitalized at John H. Roger, Jr. Hospital of Cook County who tested positive for SARS-CoV-2 between October 1, 2020 and January 12, 2021. Multivariable logistic regression was used to analyze the associations between patient characteristics and symptom persistence.

RESULTS: Of 145 patients surveyed at a median follow-up period of 255 days (IQR=238-302), 80% were Black or Hispanic, and 50 (34%) reported at least 1 symptom. In multivariable logistic regression, the risk of long COVID was associated with the severity of acute COVID-19 illness, consistent with findings from population-based cohort studies.

CONCLUSIONS: Long COVID prevalence remains high 7 months to a year after an initial illness in a majority Black and Hispanic hospitalized cohort. There is a long-term and ongoing need to assess and address the burden of long COVID, especially among minority communities disproportionately affected by acute COVID-19.}, } @article {pmid37131482, year = {2023}, author = {Ulbrichtova, R and Vysehradsky, P and Bencova, A and Tatarkova, M and Osina, O and Svihrova, V and Hudeckova, H}, title = {Validation of the Slovakian Version of the "Post‑acute (Long) COVID‑19 Quality of Life Instrument" and Pilot Study.}, journal = {Patient preference and adherence}, volume = {17}, number = {}, pages = {1137-1142}, pmid = {37131482}, issn = {1177-889X}, abstract = {PURPOSE: The aim of our study was to validate a Slovakian translation of the PAC‑19QoL instrument among Slovakian patients with post COVID-19 syndrome.

PATIENTS AND METHODS: The PAC-19QoL instrument was translated into the Slovakian language and administrated to patients with post COVID-19 syndrome. Cronbach's alpha coefficient was used to analyse the internal consistency of the instrument. Construction validity was evaluated by using Pearson's correlation coefficient and Spearman's rank correlation. Scores of patients and controls were compared using Mann-Whitney U-test.

RESULTS: Forty-five asymptomatic and forty-one symptomatic participants were included. Forty-one patients with post COVID-19 syndrome completed the PAC-19QoL and EQ-5D-5L questionnaires. PAC-19QoL domain scores were significantly different between symptomatic and asymptomatic participants. All items achieved a Cronbach alpha greater than 0.7. There was a significant correlation between all domains on the test (p < 0.001), with the highest correlation of Total (r = 0.994) and Domain 1 (r = 0.991). Spearman's rank correlation analysis confirmed that the instrument items correlated with the objective PAC-19QoL examination findings.

CONCLUSION: The Slovakian version of the instrument is valid, reliable and can be a suitable tool for research and daily clinical practice among patients with post COVID-19 syndrome.}, } @article {pmid37131073, year = {2023}, author = {Achleitner, M and Steenblock, C and Dänhardt, J and Jarzebska, N and Kardashi, R and Kanczkowski, W and Straube, R and Rodionov, RN and Bornstein, N and Tselmin, S and Kaiser, F and Bucher, R and Barbir, M and Wong, ML and Voit-Bak, K and Licinio, J and Bornstein, SR}, title = {Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.}, journal = {Molecular psychiatry}, volume = {28}, number = {7}, pages = {2872-2877}, pmid = {37131073}, issn = {1476-5578}, support = {314061271//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 288034826//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; Lipoproteins, LDL ; Autoantibodies ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; *Blood Component Removal ; Inflammation ; Biomarkers ; }, abstract = {In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients. However, little is known about the mechanisms and biomarkers correlating with treatment outcomes. Here, we have analyzed in different cohorts of Long-Covid patients specific biomarkers before and after therapeutic apheresis. In patients that reported a significant improvement following two cycles of therapeutic apheresis, there was a significant reduction in neurotransmitter autoantibodies, lipids, and inflammatory markers. Furthermore, we observed a 70% reduction in fibrinogen, and following apheresis, erythrocyte rouleaux formation and fibrin fibers largely disappeared as demonstrated by dark field microscopy. This is the first study demonstrating a pattern of specific biomarkers with clinical symptoms in this patient group. It may therefore form the basis for a more objective monitoring and a clinical score for the treatment of Long-Covid and other postinfectious syndromes.}, } @article {pmid37130814, year = {2023}, author = {Golla, R and Vuyyuru, SK and Kante, B and Kedia, S and Ahuja, V}, title = {Disorders of gut-brain interaction in post-acute COVID-19 syndrome.}, journal = {Postgraduate medical journal}, volume = {99}, number = {1174}, pages = {834-843}, doi = {10.1136/pmj-2022-141749}, pmid = {37130814}, issn = {1469-0756}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Brain ; Pandemics ; }, abstract = {The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed 'long COVID-19' or 'post-acute COVID-19 syndrome'. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.}, } @article {pmid37130538, year = {2023}, author = {Teixido, L and Andreeva, E and Gartmann, J and Lemhöfer, C and Sturm, C and Gutenbrunner, C}, title = {[Outpatient rehabilitative care for patients with Long-COVID - a guideline-based clinical practice guideline].}, journal = {Laryngo- rhino- otologie}, volume = {102}, number = {7}, pages = {521-532}, doi = {10.1055/a-1985-0450}, pmid = {37130538}, issn = {1438-8685}, mesh = {Humans ; *COVID-19/epidemiology ; Outpatients ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Even after weeks and months, persisting and also newly occurring symptoms after SARS-CoV-2 infection are common and lead in many cases to a broad spectrum of impairments and participation restrictions in all areas of daily life. Scientific evidence on therapeutic options still is limited. The aim of this work is therefore to provide pragmatic treatment recommendations analogous to the current therapeutic appliances guideline.

METHOD: In addition to a search in six electronic databases, the experiences from the treatment of more than hundred affected persons from the post-COVID outpatient rehabilitation service were used. Additionally, experiences with patients with similar symptoms from other diseases were included. All authors worked together to develop the pragmatic recommendations for the treatment of the main symptoms within the framework of outpatient therapy measures. A list of recommended diagnostics and functional assessments prior to therapy was also developed.

RESULTS: For the main symptoms fatigue, dyspnoea and cognitive impairment, the catalog of therapeutic products offers a wide range of therapeutic options under the diagnosis U09.9. The therapy packages should be composed individually and adapted to the patient's performance level that regularly should be (re-)assessed. Informing the patient about possible relapses and deteriorations and how to deal with them should be also part of the treatment regimen.

DISCUSSION: Physical modalities and rehabilitation interventions should be used in out-patient rehabilitation setting for the treatment of Long-COVID. In this regard, it is also important to take into account and treat serious complications after the disease, such as post-intensive care syndrome. Due to the rapid evolution of the knowledge a frequent review of scientific papers and recommendations should be conducted. High-quality intervention studies are necessary to achieve greater evidence in this field.}, } @article {pmid37129095, year = {2023}, author = {O'Keefe, LC}, title = {Post-Acute COVID 19 Syndrome, 'Long COVID'.}, journal = {Workplace health & safety}, volume = {71}, number = {5}, pages = {263}, doi = {10.1177/21650799231164605}, pmid = {37129095}, issn = {2165-0969}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid37128534, year = {2023}, author = {Shaikh, S and Siddiqi, Z and Ukachukwu, C and Mehkari, Z and Khan, S and Pamurthy, K and Jahan, F and Brown, A}, title = {COVID-19: Post-recovery Manifestations.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36886}, pmid = {37128534}, issn = {2168-8184}, abstract = {Background Post-COVID-19 syndrome, also known as long COVID, is a disorder that has many characteristics, one of which is chronic fatigue following acute infection with the SARS-CoV-2 virus. Methodology We distributed a web-based survey among patients diagnosed with COVID-19 across the world and collected 190 responses regarding their demographics, histories, COVID-19 infection courses, and common symptoms. Results We found that about 85.3% of the patients experienced some form of symptom following recovery from the infection. Among the reported symptoms, 59% of patients experienced fatigue or lethargy, 48.9% reported decreased stamina, 32.6% reported shortness of breath, 16.8% had a persistent cough, and 23.7% experienced anxiety following recovery from COVID-19. Conclusions Reported symptoms closely resembled myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a deeper biochemical understanding of ME/CFS is required to confirm causation.}, } @article {pmid37128500, year = {2023}, author = {García-Meléndez, DD and Morales-Casado, MI and Quintana Castro, P and Marsal Alonso, C}, title = {Persistent olfactory dysfunction in mild COVID-19 patients: A descriptive study of the characteristics and association with other symptoms.}, journal = {Medicina clinica (English ed.)}, volume = {160}, number = {8}, pages = {347-351}, pmid = {37128500}, issn = {2387-0206}, abstract = {INTRODUCTION: Post-COVID olfactory dysfunction continues to be studied due to the controversy of the mechanisms involved. The aim was to investigate the olfactory dysfunctions in association with other post-COVID symptoms.

MATERIAL AND METHODS: Observational, descriptive and single-center study. The patients had confirmed mild COVID-19 and subjective olfactory dysfunction of more than a month of evolution, which was assessed by Sniffin' Sticks Olfactory Test.

RESULTS: A total of 86 patients participated. The mean age was 37.2 years (SD 9.82). 70.9% reported parosmia and 46.5% symptoms of brain fog. A pathological test result was obtained in 72.1% of the participants. The most failed pen was 11 (apple) in 76.7%. Anosmia of pen 15 (anise) was reported more frequently in 24.4% and cacosmia of pen 9 (garlic) in 27.9%. We observed a significant association between patients who reported parosmias and brain fog (RR 2.18; p = 0.018), also between parosmia and phantosmia (RR 6.042; p < 0.001).

CONCLUSION: There is some pathological selectivity for certain test pens, a higher prevalence of cognitive symptoms and many patients with combined parosmia and brain fog.}, } @article {pmid37128299, year = {2023}, author = {Morán Blanco, JI and Alvarenga Bonilla, JA and Fremont-Smith, P and Villar Gómez de Las Heras, K}, title = {Antihistamines as an early treatment for Covid-19.}, journal = {Heliyon}, volume = {9}, number = {5}, pages = {e15772}, pmid = {37128299}, issn = {2405-8440}, abstract = {Infection with SARs-COV-2 results in COVID-19 disease. Between March 2020 and August 2021, 468 COVID-19 patients confirmed by PCR or antigen test, in Yepes, Spain, received early treatment with antihistamines, adding azithromycin in selected cases. The primary endpoint is the hospitalization rate of COVID-19 patients, and the secondary endpoints are ICU admission and mortality rates. All endpoints are compared with the official Spanish rates during the time period of the study. There were 20 hospital admissions (hospitalization rate 4,3%), 5 ICU admissions (ICU admission rate 1,1%) and 3 deaths (fatality rate of 0,6%). No patients in the study required follow up treatment, which suggest they did not develop long COVID. Results from this retrospective trail indicate that early treatment of SARS-COV-2 positive patients with antihistamines may reduce the odds of hospitalization (OR: 0.490, CI: 0.313-0.767, p-value: 0.001). Randomized controlled clinical trials are needed to further evaluate the effects of early antihistamine treatment of SARS-CoV-2 patients to prevent hospitalization, ICU admission, mortality and long-covid.}, } @article {pmid37127826, year = {2023}, author = {Dash, N and Verma, S}, title = {Long COVID in Children up to 12 y of Age - A Retrospective Telephonic Survey: Author's Reply.}, journal = {Indian journal of pediatrics}, volume = {90}, number = {8}, pages = {844}, pmid = {37127826}, issn = {0973-7693}, mesh = {Humans ; Child ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; SARS-CoV-2 ; Surveys and Questionnaires ; }, } @article {pmid37127292, year = {2023}, author = {Maes, M and Almulla, AF and Al-Hakeim, HK}, title = {Increased insulin resistance is associated with depressive symptoms due to Long COVID.}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {45}, number = {4}, pages = {380-381}, pmid = {37127292}, issn = {1809-452X}, } @article {pmid37126363, year = {2023}, author = {El-Maradny, YA and Rubio-Casillas, A and Uversky, VN and Redwan, EM}, title = {Intrinsic factors behind long-COVID: I. Prevalence of the extracellular vesicles.}, journal = {Journal of cellular biochemistry}, volume = {124}, number = {5}, pages = {656-673}, doi = {10.1002/jcb.30415}, pmid = {37126363}, issn = {1097-4644}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; *Extracellular Vesicles ; }, abstract = {It can be argued that the severity of COVID-19 has decreased in many countries. This could be a result of the broad coverage of the population by vaccination campaigns, which often reached an almost compulsory status in many places. Furthermore, significant roles were played by the multiple mutations in the body of the virus, which led to the emergence of several new SARS-CoV-2 variants with enhanced infectivity but dramatically reduced pathogenicity. However, the challenges associated with the development of various side effects and their persistence for long periods exceeding 20 months as a result of the SARS-CoV-2 infection, or taking available vaccines against it, are spreading horizontally and vertically in number and repercussions. For example, the World Health Organization announced that there are more than 17 million registered cases of long-COVID (also known as post-COVID syndrome) in the European Union countries alone. Furthermore, by using the PubMed search engine, one can find that more than 10 000 articles have been published focusing exclusively on long-COVID. In light of these enormous and ever-increasing numbers of cases and published articles, most of which are descriptive of the various long-COVID symptoms, the need to know the reasons behind this phenomenon raises several important questions. Is long-COVID caused by the continued presence of the virus or one/several of its components in the recovering individual body for long periods of time, which urges the body to respond in a way that leads to long-COVID development? Or are there some latent and limited reasons related to the recovering patients themselves? Or is it a sum of both? Many observations support a positive answer to the first question, whereas others back the second question but typically without releasing a fundamental reason/signal behind it. Whatever the answer is, it seems that the real reasons behind this widespread phenomenon remain unclear. This report opens a series of articles, in which we will try to shed light on the underlying causes that could be behind the long-COVID phenomenon.}, } @article {pmid37126052, year = {2023}, author = {Wezenbeek, E and Denolf, S and Bourgois, JG and Philippaerts, RM and De Winne, B and Willems, TM and Witvrouw, E and Verstockt, S and Schuermans, J}, title = {Impact of (long) COVID on athletes' performance: a prospective study in elite football players.}, journal = {Annals of medicine}, volume = {55}, number = {1}, pages = {2198776}, pmid = {37126052}, issn = {1365-2060}, mesh = {Humans ; Male ; *Football/physiology ; Prospective Studies ; *Athletic Performance/physiology ; *COVID-19 ; SARS-CoV-2 ; Athletes ; }, abstract = {OBJECTIVES: To investigate possible persistent performance deficits after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in elite athletes.

METHODS: A prospective cohort study in three Belgian professional male football teams was performed during the 2020 - 2021 season. Participants were submitted to strength, jump, and sprint tests and an aerobic performance test (the Yo-Yo Intermittent Recovery test (YYIR)). These tests were repeated at fixed time intervals throughout the season. Assessment of SARS-CoV-2 infection was performed by a polymerase chain reaction (PCR) test before each official game.

RESULTS: Of the 84 included participants, 22 were infected with SARS-CoV-2 during follow-up. At the first testing after infection (52.0 ± 11.2 days after positive PCR testing) significantly higher percentages of maximal heart rate (%HRmax) were seen - within the isolated group of infected players- during (p = .006) and after the YYIR (2 min after, p = .013), compared to pre-infection data. This increase in %HRmax was resolved at the second YYIR testing after infection (127.6 ± 33.1 days after positive PCR testing). Additionally, when comparing the first test after infection in formerly infected to non-infected athletes, significantly higher %HRmax were found during (p < .001) and after the YYIR test (p < .001),No significant deficits were found for the jump, muscular strength or sprint tests.

UNLABELLED: Aerobic performance seems compromised even weeks after infection. Simultaneously, anaerobic performance seemed to be spared. Because of the potential detrimental effects on the immune system, caution might be advised with high-intensity exposure until aerobic performance is restored.KEY MESSAGESElite football players' aerobic performance seems to be affected for weeks after they return to sports after a SARS-CoV-2 infection.Similarly, anaerobic performance tests showed no discernible changes between both before and after SARS-CoV-2 infections.Regular YYIR testing is recommended to monitor aerobic performance after SARS-CoV-2 infection.}, } @article {pmid37125676, year = {2023}, author = {Koh, YC and Ho, CT and Pan, MH}, title = {The Role of Mitochondria in Phytochemically Mediated Disease Amelioration.}, journal = {Journal of agricultural and food chemistry}, volume = {71}, number = {18}, pages = {6775-6788}, doi = {10.1021/acs.jafc.2c08921}, pmid = {37125676}, issn = {1520-5118}, mesh = {Humans ; Resveratrol/pharmacology ; *Curcumin/pharmacology/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Mitochondria/metabolism ; Mitochondrial Dynamics ; }, abstract = {Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit oxidative stress and preserve membrane potential, induce mitochondrial biogenesis, balance mitochondrial fusion and fission, and enhance the functionality of the electron transport chain. However, there are only a few studies suggesting that phytochemicals could potentially protect against the cytotoxicity of some current cancer drugs, especially those that damage mitochondria. Besides, COVID-19 and long COVID have also been reported to be correlated to mitochondrial dysfunction. Curcumin has been reported bringing a positive impact on COVID-19 and long COVID. Therefore, in this study, the benefits of resveratrol and curcumin to be applied for cancer treatment/prevention and disease amelioration were reviewed. Besides, this review also provides some perspectives on phytochemicals to be considered as a treatment adjuvant for COVID-19 and long COVID by targeting mitochondrial rescue. Hopefully, this review can provide new insight into disease treatment with phytochemicals targeting mitochondria.}, } @article {pmid37125400, year = {2023}, author = {O'Mahoney, LL and Routen, A and Gillies, C and Khunti, K}, title = {Response to "Was the rate of Long Covid as high as 45%-a scary report with flaw".}, journal = {EClinicalMedicine}, volume = {59}, number = {}, pages = {101950}, pmid = {37125400}, issn = {2589-5370}, } @article {pmid37125399, year = {2023}, author = {Yao, L and Wang, G and Aleya, L and Maida, M and Graff, JC and Sun, D and Gu, W}, title = {Was the rate of Long Covid as high as 45%-a scary report with flaw.}, journal = {EClinicalMedicine}, volume = {59}, number = {}, pages = {101949}, pmid = {37125399}, issn = {2589-5370}, } @article {pmid37122723, year = {2023}, author = {van der Togt, V and Rossman, JS}, title = {Hypothesis: inflammatory acid-base disruption underpins Long Covid.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1150105}, pmid = {37122723}, issn = {1664-3224}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Acid-Base Equilibrium ; Inflammation ; }, abstract = {The mechanism of Long Covid (Post-Acute Sequelae of COVID-19; PASC) is currently unknown, with no validated diagnostics or therapeutics. SARS-CoV-2 can cause disseminated infections that result in multi-system tissue damage, dysregulated inflammation, and cellular metabolic disruptions. The tissue damage and inflammation has been shown to impair microvascular circulation, resulting in hypoxia, which coupled with virally-induced metabolic reprogramming, increases cellular anaerobic respiration. Both acute and PASC patients show systemic dysregulation of multiple markers of the acid-base balance. Based on these data, we hypothesize that the shift to anaerobic respiration causes an acid-base disruption that can affect every organ system and underpins the symptoms of PASC. This hypothesis can be tested by longitudinally evaluating acid-base markers in PASC patients and controls over the course of a month. If our hypothesis is correct, this could have significant implications for our understanding of PASC and our ability to develop effective diagnostic and therapeutic approaches.}, } @article {pmid37122328, year = {2023}, author = {Karampitsakos, T and Sotiropoulou, V and Katsaras, M and Tsiri, P and Georgakopoulou, VE and Papanikolaou, IC and Bibaki, E and Tomos, I and Lambiri, I and Papaioannou, O and Zarkadi, E and Antonakis, E and Pandi, A and Malakounidou, E and Sampsonas, F and Makrodimitri, S and Chrysikos, S and Hillas, G and Dimakou, K and Tzanakis, N and Sipsas, NV and Antoniou, K and Tzouvelekis, A}, title = {Corrigendum: Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1194925}, doi = {10.3389/fmed.2023.1194925}, pmid = {37122328}, issn = {2296-858X}, abstract = {[This corrects the article DOI: 10.3389/fmed.2022.1083264.].}, } @article {pmid37122293, year = {2023}, author = {Saucier, J and Jose, C and Beroual, Z and Al-Qadi, M and Chartrand, S and Libert, E and Losier, MC and Cooling, K and Girouard, G and Jbilou, J and Chamard-Witkowski, L}, title = {Cognitive inhibition deficit in long COVID-19: An exploratory study.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1125574}, pmid = {37122293}, issn = {1664-2295}, abstract = {BACKGROUND AND OBJECTIVES: An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition.

METHODOLOGY: A cross-sectional research design was adopted to compare four sub-samples recruited over a 16-month timeframe (1-4, 5-8, 9-12, and 13-16 months). Phone interviews were conducted at least 6 weeks after being infected by COVID-19. Sociodemographic and clinical questionnaires were administered followed by standardized neurocognitive and psychological tests and health questionnaires screening cognitive symptoms, anxiety, depression, fatigue, and autonomy.

RESULTS: Regarding general health questionnaires, 55.2% of the 134 participants had symptoms of psychiatric illness, while 21.6% of patients had moderate-to-severe anxiety or depression. Cognitive efficiency was diminished in 19.4% of our population. Executive dysfunction was screened in 56% of patients, and an impairment of cognitive flexibility and inhibition was revealed in 38.8%. Depression, hospital or intensive care unit (ICU) admission, and the duration of hospital or ICU stay were associated with an inhibition deficit. The duration elapsed from the initial infection, and the neurocognitive assessment was not associated with a decrease in inhibition deficit. The prevalence of cognitive impairments, other than inhibition deficit, tended to decrease during the study period.

DISCUSSION: This study supports the extensive literature on the cognitive and neuropsychiatric sequelae of COVID-19 and highlights long-lasting inhibition deficits, while other cognitive functions seemed to improve over time. The severity of infection could interact as a catalyst in the complex interplay between depression and executive functions. The absence of a relation between inhibition deficits and sociodemographic or medical factors reinforces the need for cognitive screening in all COVID-19 patients. Future research should focus on inhibition deficits longitudinally to assess the progression of this impairment.}, } @article {pmid37122243, year = {2023}, author = {Fratt, EM and Crosson, FJ}, title = {Long COVID, Disability, and the Need for Timely Health Care Coverage.}, journal = {The Permanente journal}, volume = {27}, number = {3}, pages = {7-9}, pmid = {37122243}, issn = {1552-5775}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Socioeconomic Factors ; *Disabled Persons ; Delivery of Health Care ; }, } @article {pmid37122115, year = {2023}, author = {Sharma, V and Pattnaik, S and Ahluwalia, H and Kaur, M}, title = {Pre-pandemic autonomic function as a predictor of the COVID clinical course in young adults.}, journal = {Clinical and experimental pharmacology & physiology}, volume = {50}, number = {7}, pages = {594-603}, doi = {10.1111/1440-1681.13776}, pmid = {37122115}, issn = {1440-1681}, mesh = {Humans ; Young Adult ; Retrospective Studies ; *Pandemics ; Heart Rate/physiology ; *COVID-19 ; Autonomic Nervous System ; }, abstract = {Long coronavirus disease (COVID) is emerging as a common clinical entity in the current era. Autonomic dysfunction is one of the frequently reported post-COVID complications. We hypothesize a bi-directional relationship between the autonomic function and the COVID course. This postulation has been inadequately addressed in the literature. A retrospective cohort (pre and post-comparison) study was conducted on 30 young adults whose pre-COVID autonomic function test results were available. They were divided into case and control groups based on whether they tested reverse transcription polymerase chain reaction positive for COVID-19. Autonomic function tests were performed in both the case and control groups. COVID infection in healthy young adults shifts the sympatho-vagal balance from the pre-disease state. Postural orthostatic tachycardia syndrome was present in 35% of the COVID-affected group. COVID course parameters were found to be associated with parasympathetic reactivity and the baroreflex function. Baseline autonomic function (parasympathetic reactivity represented by Δ heart rate changes during deep breathing and 30:15 ratio during lying-to-standing test) was also associated with the COVID course, the post-COVID symptoms and the post-COVID autonomic function profile. Additionally, multiple regression analysis found that the baseline parasympathetic reactivity was a very important determinant of the clinical course of COVID, the post-COVID symptoms and the post-COVID autonomic profile. Sympatho-vagal balance shifts to parasympathetic withdrawal with sympathetic predominance due to COVID infection in healthy young adults. There is a bi-directional relationship between the autonomic function and the COVID course.}, } @article {pmid37120076, year = {2023}, author = {Kamata, K and Honda, H and Tokuda, Y and Takamatsu, A and Taniguchi, K and Shibuya, K and Tabuchi, T}, title = {Post-COVID health-related quality of life and somatic symptoms: A national survey in Japan.}, journal = {The American journal of the medical sciences}, volume = {366}, number = {2}, pages = {114-123}, pmid = {37120076}, issn = {1538-2990}, mesh = {Female ; Humans ; Middle Aged ; Quality of Life ; Health Status ; *Medically Unexplained Symptoms ; Japan/epidemiology ; Cross-Sectional Studies ; *COVID-19/epidemiology/therapy ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: The characteristics and risk factors of post-COVID-19 condition affecting health-related quality of life and the symptom burden are unclear.

METHODS: The present, cross-sectional study used the JASTIS (Japan Society and New Tobacco Internet Survey) database. EQ-5D-5L and Somatic Symptom Scale-8 were used to assess health-related quality of life and somatic symptoms, respectively. The participants were classified into a no-COVID-19, COVID-19 not requiring oxygen therapy or COVID-19 requiring oxygen therapy group. First, the entire cohort was analyzed. Then, sensitivity analysis was performed after excluding patients in the no-COVID-19 group with a history of close contact with individuals known to have the disease.

FINDINGS: In total, 30130 individuals (mean age: 47.8; females: 51.2%), including 539 and 805 with COVID-19 requiring and not requiring oxygen therapy, respectively, participated. The analysis of the entire cohort as well as the sensitivity analysis demonstrated that individuals with a history of COVID-19 had significantly lower EQ-5D-5L and significantly higher SSS-8 scores than those with no COVID-19 history. The group requiring oxygen therapy was associated with significantly lower EQ-5D-5L and higher SSS-8 scores than the group not requiring oxygen therapy. Propensity-score matching confirmed these results. Furthermore, two or more COVID-19 vaccinations were independently associated with high EQ-5D-5L and low SSS-8 scores (P < 0.001).

CONCLUSIONS: The participants with a COVID-19 history, especially those with severe disease, had a significantly higher somatic symptom burden. Analysis after adjusting for potential confounders found that their quality-of-life was also severely affected. Vaccination is crucial to addressing these symptoms, especially in high-risk patients.}, } @article {pmid37116351, year = {2023}, author = {Chiang, CY and Lin, YJ and Weng, WT and Lin, HD and Lu, CY and Chen, WJ and Shih, CY and Lin, PY and Lin, SZ and Ho, TJ and Shibu, MA and Huang, CY}, title = {Recuperative herbal formula Jing Si maintains vasculature permeability balance, regulates inflammation and assuages concomitants of "Long-Covid".}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {163}, number = {}, pages = {114752}, pmid = {37116351}, issn = {1950-6007}, mesh = {Mice ; Humans ; Animals ; Post-Acute COVID-19 Syndrome ; Lipopolysaccharides/adverse effects ; Cytokine Release Syndrome ; Cytokines/metabolism ; *COVID-19 ; Inflammation/drug therapy/metabolism ; *Acute Lung Injury/metabolism ; NF-kappa B/metabolism ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a worldwide health threat that has long-term effects on the patients and there is currently no efficient cure prescribed for the treatment and the prolonging effects. Traditional Chinese medicines (TCMs) have been reported to exert therapeutic effect against COVID-19. In this study, the therapeutic effects of Jing Si herbal tea (JSHT) against COVID-19 infection and associated long-term effects were evaluated in different in vitro and in vivo models. The anti-inflammatory effects of JSHT were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in Omicron pseudotyped virus-induced acute lung injury model. The effect of JSHT on cellular stress was determined in HK-2 proximal tubular cells and H9c2 cardiomyoblasts. The therapeutic benefits of JSHT on anhedonia and depression symptoms associated with long COVID were evaluated in mice models for unpredictable chronic mild stress (UCMS). JSHT inhibited the NF-ƙB activities, and significantly reduced LPS-induced expression of TNFα, COX-2, NLRP3 inflammasome, and HMGB1. JSHT was also found to significantly suppress the production of NO by reducing iNOS expression in LPS-stimulated RAW 264.7 cells. Further, the protective effects of JSHT on lung tissue were confirmed based on mitigation of lung injury, repression in TMRRSS2 and HMGB-1 expression and reduction of cytokine storm in the Omicron pseudotyped virus-induced acute lung injury model. JSHT treatment in UCMS models also relieved chronic stress and combated depression symptoms. The results therefore show that JSHT attenuates the cytokine storm by repressing NF-κB cascades and provides the protective functions against symptoms associated with long COVID-19 infection.}, } @article {pmid37114441, year = {2024}, author = {Gutti, G and He, Y and Coldren, WH and Lalisse, RF and Border, SE and Hadad, CM and McElroy, CA and Ekici, ÖD}, title = {In-silico guided design, screening, and molecular dynamic simulation studies for the identification of potential SARS-CoV-2 main protease inhibitors for the targeted treatment of COVID-19.}, journal = {Journal of biomolecular structure & dynamics}, volume = {42}, number = {4}, pages = {1733-1750}, doi = {10.1080/07391102.2023.2202247}, pmid = {37114441}, issn = {1538-0254}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Molecular Dynamics Simulation ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/pharmacology/chemistry ; Protease Inhibitors/pharmacology/chemistry ; Peptides ; Epoxy Compounds ; Molecular Docking Simulation ; *Coronavirus 3C Proteases ; }, abstract = {COVID-19, the disease responsible for the recent pandemic, is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main protease (Mpro) of SARS-CoV-2 is an essential proteolytic enzyme that plays a number of important roles in the replication of the virus in human host cells. Blocking the function of SARS-CoV-2 Mpro offers a promising and targeted, therapeutic option for the treatment of the COVID-19 infection. Such an inhibitory strategy is currently successful in treating COVID-19 under FDA's emergency use authorization, although with limited benefit to the immunocompromised along with an unfortunate number of side effects and drug-drug interactions. Current COVID vaccines protect against severe disease and death but are mostly ineffective toward long COVID which has been seen in 5-36% of patients. SARS-CoV-2 is a rapidly mutating virus and is here to stay endemically. Hence, alternate therapeutics to treat SARS-CoV-2 infections are still needed. Moreover, because of the high degree of conservation of Mpro among different coronaviruses, any newly developed antiviral agents should better prepare us for potential future epidemics or pandemics. In this paper, we first describe the design and computational docking of a library of novel 188 first-generation peptidomimetic protease inhibitors using various electrophilic warheads with aza-peptide epoxides, α-ketoesters, and β-diketones identified as the most effective. Second-generation designs, 192 compounds in total, focused on aza-peptide epoxides with drug-like properties, incorporating dipeptidyl backbones and heterocyclic ring motifs such as proline, indole, and pyrrole groups, yielding 8 hit candidates. These novel and specific inhibitors for SARS-CoV-2 Mpro can ultimately serve as valuable alternate and broad-spectrum antivirals against COVID-19.Communicated by Ramaswamy H. Sarma.}, } @article {pmid37113165, year = {2023}, author = {Sarmiento Varón, L and González-Puelma, J and Medina-Ortiz, D and Aldridge, J and Alvarez-Saravia, D and Uribe-Paredes, R and Navarrete, MA}, title = {The role of machine learning in health policies during the COVID-19 pandemic and in long COVID management.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1140353}, pmid = {37113165}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Health Policy ; Machine Learning ; }, abstract = {The ongoing COVID-19 pandemic is arguably one of the most challenging health crises in modern times. The development of effective strategies to control the spread of SARS-CoV-2 were major goals for governments and policy makers. Mathematical modeling and machine learning emerged as potent tools to guide and optimize the different control measures. This review briefly summarizes the SARS-CoV-2 pandemic evolution during the first 3 years. It details the main public health challenges focusing on the contribution of mathematical modeling to design and guide government action plans and spread mitigation interventions of SARS-CoV-2. Next describes the application of machine learning methods in a series of study cases, including COVID-19 clinical diagnosis, the analysis of epidemiological variables, and drug discovery by protein engineering techniques. Lastly, it explores the use of machine learning tools for investigating long COVID, by identifying patterns and relationships of symptoms, predicting risk indicators, and enabling early evaluation of COVID-19 sequelae.}, } @article {pmid37112878, year = {2023}, author = {Soares, SR and da Silva Torres, MK and Lima, SS and de Sarges, KML and Santos, EFD and de Brito, MTFM and da Silva, ALS and de Meira Leite, M and da Costa, FP and Cantanhede, MHD and da Silva, R and de Oliveira Lameira Veríssimo, A and Vallinoto, IMVC and Feitosa, RNM and Quaresma, JAS and Chaves, TDSS and Viana, GMR and Falcão, LFM and Santos, EJMD and Vallinoto, ACR and da Silva, ANMR}, title = {Antibody Response to the SARS-CoV-2 Spike and Nucleocapsid Proteins in Patients with Different COVID-19 Clinical Profiles.}, journal = {Viruses}, volume = {15}, number = {4}, pages = {}, pmid = {37112878}, issn = {1999-4915}, mesh = {Humans ; Antibodies, Viral ; Antibody Formation ; *COVID-19 ; Immunoglobulin G ; Nucleocapsid Proteins ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; }, abstract = {The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19.}, } @article {pmid37112866, year = {2023}, author = {da Silva, R and de Sarges, KML and Cantanhede, MHD and da Costa, FP and Dos Santos, EF and Rodrigues, FBB and de Nazaré do Socorro de Almeida Viana, M and de Meira Leite, M and da Silva, ALS and de Brito, MTM and da Silva Torres, MK and Queiroz, MAF and Vallinoto, IMVC and Henriques, DF and Dos Santos, CP and Viana, GMR and Quaresma, JAS and Falcão, LFM and Vallinoto, ACR and Dos Santos, EJM}, title = {Thrombophilia and Immune-Related Genetic Markers in Long COVID.}, journal = {Viruses}, volume = {15}, number = {4}, pages = {}, pmid = {37112866}, issn = {1999-4915}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Gene Frequency ; Genetic Markers ; Cross-Sectional Studies ; *COVID-19/genetics ; Genotype ; Genetic Predisposition to Disease ; *Thrombophilia/genetics ; Polymorphism, Single Nucleotide ; Case-Control Studies ; }, abstract = {Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.}, } @article {pmid37112859, year = {2023}, author = {Galúcio, VCA and Menezes, DC and Lima, PDL and Palácios, VRDCM and Vasconcelos, PFDC and Quaresma, JAS and Falcão, LFM}, title = {Evaluation of the Hematological Patterns from Up to 985 Days of Long COVID: A Cross-Sectional Study.}, journal = {Viruses}, volume = {15}, number = {4}, pages = {}, pmid = {37112859}, issn = {1999-4915}, mesh = {Humans ; *COVID-19 ; Cross-Sectional Studies ; Erythrocyte Indices ; Hematologic Tests ; Erythrocytes ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID affects many individuals following acute coronavirus disease 2019 (COVID-19), and hematological changes can persist after the acute COVID-19 phase. This study aimed to evaluate these hematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a 'long COVID' clinical care program in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected to quantify erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalized in the acute phase had higher mean red/white blood cell, platelet, and plateletcrit levels and red blood cell distribution width. Furthermore, hematimetric parameters were higher in shorter periods of long COVID than in longer periods. Patients with more than six concomitant long COVID symptoms had a higher white blood cell count, a shorter prothrombin time (PT), and increased PT activity. Our results indicate there may be a compensatory mechanism for erythrogram-related markers within 985 days of long COVID. Increased levels of leukogram-related markers and coagulation activity were observed in the worst long COVID groups, indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.}, } @article {pmid37109328, year = {2023}, author = {Galluzzo, V and Zazzara, MB and Ciciarello, F and Tosato, M and Bizzarro, A and Paglionico, A and Varriano, V and Gremese, E and Calvani, R and Landi, F and , }, title = {Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms.}, journal = {Journal of clinical medicine}, volume = {12}, number = {8}, pages = {}, pmid = {37109328}, issn = {2077-0383}, abstract = {Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.}, } @article {pmid37108606, year = {2023}, author = {Stufano, A and Isgrò, C and Palese, LL and Caretta, P and De Maria, L and Lovreglio, P and Sardanelli, AM}, title = {Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers.}, journal = {International journal of molecular sciences}, volume = {24}, number = {8}, pages = {}, pmid = {37108606}, issn = {1422-0067}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Oxidative Stress/physiology ; Italy/epidemiology ; }, abstract = {In addition to the acute symptoms after infection, patients and society are also being challenged by the long-term effects of COVID-19, known as long COVID. Oxidative stress, as a pivotal point in the pathophysiology of COVID-19, could potentially be also involved in the development of the post-COVID syndrome. The aim of the present study was to evaluate the relationship between changes in oxidative status and the persistence of long-COVID symptoms in workers with a previous mild COVID-19 infection. A cross-sectional study was conducted among 127 employees of an Italian university (80 with a previous COVID-19 infection, and 47 healthy subjects). The TBARS assay was used to detect malondialdehyde serum levels (MDA), while total hydroperoxide (TH) production was measured by a d-ROMs kit. A significant difference in mean serum MDA values was found between previously infected subjects and healthy controls and (4.9 µm vs. 2.8 µm, respectively). Receiver-operating characteristic (ROC) curves showed high specificity and good sensibility (78.7% and 67.5%, respectively) for MDA serum levels. A random forest classifier identified the hematocrit value, MDA serum levels, and IgG titer against SARS-CoV-2 as features with the highest predictive value in distinguishing 34 long-COVID from 46 asymptomatic post-COVID subjects. Oxidative damage persists in subjects with previous COVID-19 infection, suggesting a possible role of oxidative stress mediators in the pathogenesis of long COVID.}, } @article {pmid37107929, year = {2023}, author = {Suh, HW and Kwon, CY and Lee, B}, title = {Long-Term Impact of COVID-19 on Heart Rate Variability: A Systematic Review of Observational Studies.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {37107929}, issn = {2227-9032}, support = {IITP-2023-2020-0-01791//Ministry of Science and ICT/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) sequelae (or long COVID) has become a clinically significant concern. Several studies have reported the relationship between heart rate variability (HRV) parameters and COVID-19. This review investigates the long-term association between COVID-19 and HRV parameters. Four electronic databases were searched up to 29 July 2022. We included observational studies comparing HRV parameters (measurement durations: 1 min or more) in participants with and without a history of COVID-19. We used assessment tools developed by the National Heart, Lung, and Blood Institute group to evaluate the methodological quality of included studies. Eleven cross-sectional studies compared HRV parameters in individuals who recovered from acute COVID-19 infection to controls (n = 2197). Most studies reported standard deviation of normal-to-normal intervals (SDNN) and root mean square of the successive differences. The methodological quality of the included studies was not optimal. The included studies generally found decreased SDNN and parasympathetic activity in post-COVID-19 individuals. Compared to controls, decreases in SDNN were observed in individuals who recovered from COVID-19 or had long COVID. Most of the included studies emphasized parasympathetic inhibition in post-COVID-19 conditions. Due to the methodological limitations of measuring HRV parameters, the findings should be further validated by robust prospective longitudinal studies.}, } @article {pmid37106076, year = {2023}, author = {Seifart, U}, title = {Post-COVID-More than chronic fatigue?.}, journal = {Herz}, volume = {48}, number = {3}, pages = {229-233}, pmid = {37106076}, issn = {1615-6692}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/therapy ; Microcirculation ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/epidemiology ; }, abstract = {After the first COVID-19 survivors were medically treated in Germany from spring 2020 onwards, various courses of the disease emerged that, in addition to the acute infection, led to prolonged symptoms (long COVID), but also to a symptomatic course beyond 12 weeks, which is referred to as "post-COVID syndrome" (PCS). Currently, the incidence of PCS is estimated to be approximately 15% of all symptomatically infected patients, although over- or underestimations may occur due to the soft definition and lack of control groups. The etiology of PCS is currently unknown. The following pathogenetic processes are discussed in particular: an endothelial dysfunction with microcirculatory disturbances and subsequent organ damage, a residual virus or virus particles, and/or an excessive autoimmune process. Due to the large number of organs that may be affected, PCS presents as a very complex clinical picture with up to 200 described symptoms. An evidence-based causal therapy for PCS has not yet been established. The guideline-based inpatient rehabilitation measures adapted to the individual patient resources have proven to be an effective therapy and should therefore be involved in the therapeutic concept at an early stage. Post-COVID syndrome is a multicomplex disease that can have a considerable impact on the quality of life, but also on the professional performance of the affected patients. Thus, it is clearly more than just a chronic fatigue syndrome. In the interest of our patients, treating physicians should take this disease seriously, clarify the differential diagnoses, and provide sensitive therapeutic care.}, } @article {pmid37105737, year = {2023}, author = {van der Feltz-Cornelis, C and Heightman, M and Allsopp, G}, title = {Learning from long COVID: integrated care for multiple long-term conditions.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {73}, number = {730}, pages = {196-197}, pmid = {37105737}, issn = {1478-5242}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Long-Term Care ; *Delivery of Health Care, Integrated ; }, } @article {pmid37105729, year = {2023}, author = {König, BH and van Jaarsveld, CH and Bischoff, EW and Schers, HJ and Lucassen, PL and Olde Hartman, TC}, title = {Prognostic factors for persistent fatigue after COVID-19: a prospective matched cohort study in primary care.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {73}, number = {730}, pages = {e340-e347}, pmid = {37105729}, issn = {1478-5242}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Cohort Studies ; Prognosis ; Fatigue/epidemiology/etiology ; Primary Health Care ; }, abstract = {BACKGROUND: Persistent fatigue after COVID-19 is common; however, the exact incidence and prognostic factors differ between studies. Evidence suggests that age, female sex, high body mass index, and comorbidities are risk factors for long COVID.

AIM: To investigate the prevalence of persistent fatigue after COVID-19 in patients with a mild infection (managed in primary care) during the first wave of the pandemic and to determine prognostic factors for persistent fatigue.

DESIGN AND SETTING: This was a prospective cohort study in Dutch general practice, combining online questionnaires with data from electronic health records.

METHOD: Patients who contacted their GP between March and May 2020 and were diagnosed with COVID-19 during the first wave of the pandemic were included. Patients were matched to controls without COVID-19 based on age, sex, and GP practice. Fatigue was measured at 3, 6, and 15 months, using the Checklist of Individual Strength.

RESULTS: All the participants were GP attendees and included 179 with suspected COVID-19, but who had mild COVID and who had not been admitted to hospital with COVID, and 122 without suspected COVID-19. Persistent fatigue was present in 35% (49/142) of the suspected COVID-19 group and 13% (14/109) of the non-COVID-19 group (odds ratio 3.65; 95% confidence interval = 1.82 to 7.32). Prognostic factors for persistent fatigue included low education level, absence of a partner, high neuroticism (using the Eysenck Personality Questionnaire Revised-Short Form), low resilience, high frequency of GP contact, medication use, and threatening experiences in the past. The latter three factors appeared to be prognostic factors for persistent fatigue specifically after COVID-19 infection.

CONCLUSION: GP patients with COVID-19 (who were not admitted to hospital with COVID) have a fourfold higher chance of developing persistent fatigue than GP patients who had not had COVID-19. This risk is even higher in psychosocially vulnerable patients who had COVID-19.}, } @article {pmid37104928, year = {2023}, author = {Muccioli, L and Sighinolfi, G and Mitolo, M and Ferri, L and Jane Rochat, M and Pensato, U and Taruffi, L and Testa, C and Masullo, M and Cortelli, P and Lodi, R and Liguori, R and Tonon, C and Bisulli, F}, title = {Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction.}, journal = {NeuroImage. Clinical}, volume = {38}, number = {}, pages = {103410}, pmid = {37104928}, issn = {2213-1582}, mesh = {Female ; Humans ; Infant ; Smell ; *Olfaction Disorders/diagnostic imaging/etiology ; Anosmia ; *COVID-19 ; Cognition ; *Cognitive Dysfunction ; }, abstract = {OBJECTIVES: To explore the neuropsychological profile and the integrity of the olfactory network in patients with COVID-19-related persistent olfactory dysfunction (OD).

METHODS: Patients with persistent COVID-19-related OD underwent olfactory assessment with Sniffin' Sticks and neuropsychological evaluation. Additionally, both patients and a control group underwent brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI) sequences on a 3 T scanner. Morphometrical properties were evaluated in olfaction-associated regions; the rs-fMRI data were analysed using graph theory at the whole-brain level and within a standard parcellation of the olfactory functional network. All the MR-derived quantities were compared between the two groups and their correlation with clinical scores in patients were explored.

RESULTS: We included 23 patients (mean age 37 ± 14 years, 12 females) with persistent (mean duration 11 ± 5 months, range 2-19 months) COVID-19-related OD (mean score 23.63 ± 5.32/48, hyposmia cut-off: 30.75) and 26 sex- and age-matched healthy controls. Applying population-derived cut-off values, the two cognitive domains mainly impaired were visuospatial memory and executive functions (17 % and 13 % of patients). Brain MRI did not show gross morphological abnormalities. The lateral orbital cortex, hippocampus, and amygdala volumes exhibited a reduction trend in patients, not significant after the correction for multiple comparisons. The olfactory bulb volumes did not differ between patients and controls. Graph analysis of the functional olfactory network showed altered global and local properties in the patients' group (n = 19, 4 excluded due to artifacts) compared to controls. Specifically, we detected a reduction in the global modularity coefficient, positively correlated with hyposmia severity, and an increase of the degree and strength of the right thalamus functional connections, negatively correlated with short-term verbal memory scores.

DISCUSSION: Patients with persistent COVID-19-related OD showed an altered olfactory network connectivity correlated with hyposmia severity and neuropsychological performance. No significant morphological alterations were found in patients compared with controls.}, } @article {pmid37104709, year = {2023}, author = {Márquez, NG and Jamal, A and Johnston, R and Richter, EI and Gorbach, PM and Vannorsdall, TD and Rubin, LH and Jennings, C and Landay, AL and Peluso, MJ and Antar, AAR}, title = {Characterizing Symptoms and Identifying Biomarkers of Long COVID in People With and Without HIV: Protocol for a Remotely Conducted Prospective Observational Cohort Study.}, journal = {JMIR research protocols}, volume = {12}, number = {}, pages = {e47079}, pmid = {37104709}, issn = {1929-0748}, support = {K08 AI143391/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; P30 AI094189/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Living with HIV is a risk factor for severe acute COVID-19, but it is unknown whether it is a risk factor for long COVID.

OBJECTIVE: This study aims to characterize symptoms, sequelae, and cognition formally and prospectively 12 months following SARS-CoV-2 infection in people living with HIV compared with people without HIV. People with no history of SARS-CoV-2 infection, both with and without HIV, are enrolled as controls. The study also aims to identify blood-based biomarkers or patterns of immune dysregulation associated with long COVID.

METHODS: This prospective observational cohort study enrolled participants into 1 of the following 4 study arms: people living with HIV who had SARS-CoV-2 infection for the first time <4 weeks before enrollment (HIV+COVID+ arm), people without HIV who had SARS-CoV-2 infection for the first time within 4 weeks of enrollment (HIV-COVID+ arm), people living with HIV who believed they never had SARS-CoV-2 infection (HIV+COVID- arm), and people without HIV who believed they never had SARS-CoV-2 infection (HIV-COVID- arm). At enrollment, participants in the COVID+ arms recalled their symptoms, mental health status, and quality of life in the month before having SARS-CoV-2 infection via a comprehensive survey administered by telephone or on the web. All participants completed the same comprehensive survey 1, 2, 4, 6, and 12 months after post-acute COVID-19 symptom onset or diagnosis, if asymptomatic, (COVID+ arms) or after enrollment (COVID- arms) on the web or by telephone. In total, 11 cognitive assessments were administered by telephone at 1 and 4 months after symptom onset (COVID+ arms) or after enrollment (COVID- arms). A mobile phlebotomist met the participants at a location of their choice for height and weight measurements, orthostatic vital signs, and a blood draw. Participants in the COVID+ arms donated blood 1 and 4 months after COVID-19, and participants in the COVID- arms donated blood once or none. Blood was then shipped overnight to the receiving study laboratory, processed, and stored.

RESULTS: This project was funded in early 2021, and recruitment began in June 2021. Data analyses will be completed by summer 2023. As of February 2023, a total of 387 participants were enrolled in this study, with 345 participants having completed enrollment or baseline surveys together with at least one other completed study event. The 345 participants includes 76 (22%) HIV+COVID+, 121 (35.1%) HIV-COVID+, 78 (22.6%) HIV+COVID-, and 70 (20.3%) HIV-COVID- participants.

CONCLUSIONS: This study will provide longitudinal data to characterize COVID-19 recovery over 12 months in people living with and without HIV. Additionally, this study will determine whether biomarkers or patterns of immune dsyregulation associate with decreased cognitive function or symptoms of long COVID.

DERR1-10.2196/47079.}, } @article {pmid37103631, year = {2024}, author = {Wu, X and Xiang, M and Jing, H and Wang, C and Novakovic, VA and Shi, J}, title = {Damage to endothelial barriers and its contribution to long COVID.}, journal = {Angiogenesis}, volume = {27}, number = {1}, pages = {5-22}, pmid = {37103631}, issn = {1573-7209}, mesh = {Animals ; Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Endothelial Cells/physiology ; *Vascular Diseases ; }, abstract = {The world continues to contend with COVID-19, fueled by the emergence of viral variants. At the same time, a subset of convalescent individuals continues to experience persistent and prolonged sequelae, known as long COVID. Clinical, autopsy, animal and in vitro studies all reveal endothelial injury in acute COVID-19 and convalescent patients. Endothelial dysfunction is now recognized as a central factor in COVID-19 progression and long COVID development. Different organs contain different types of endothelia, each with specific features, forming different endothelial barriers and executing different physiological functions. Endothelial injury results in contraction of cell margins (increased permeability), shedding of glycocalyx, extension of phosphatidylserine-rich filopods, and barrier damage. During acute SARS-CoV-2 infection, damaged endothelial cells promote diffuse microthrombi and destroy the endothelial (including blood-air, blood-brain, glomerular filtration and intestinal-blood) barriers, leading to multiple organ dysfunction. During the convalescence period, a subset of patients is unable to fully recover due to persistent endothelial dysfunction, contributing to long COVID. There is still an important knowledge gap between endothelial barrier damage in different organs and COVID-19 sequelae. In this article, we mainly focus on these endothelial barriers and their contribution to long COVID.}, } @article {pmid37102989, year = {2023}, author = {Pezzuto, F and Lunardi, F and Vedovelli, L and Olteanu, GE and Fortarezza, F and De Pellegrin, A and Melan, L and Faccioli, E and De Franceschi, E and Giraudo, C and Del Vecchio, C and Marinello, S and Pasello, G and Gregori, D and Navalesi, P and Rea, F and Schiavon, M and Calabrese, F}, title = {Vascular/epithelial changes as late sequelae after recovery from SARS-COV-2 infection: an in-vivo comparative study.}, journal = {Histopathology}, volume = {83}, number = {2}, pages = {229-241}, doi = {10.1111/his.14930}, pmid = {37102989}, issn = {1365-2559}, support = {BIRD213993//University of Padova/ ; 2020A08//Intesa San Paolo Vita Bank/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Lung ; *Lung Neoplasms ; }, abstract = {AIMS: While there is partial evidence of lung lesions in patients suffering from long COVID there are substantial concerns about lung remodelling sequelae after COVID-19 pneumonia. The aim of the present retrospective comparative study was to ascertain morphological features in lung samples from patients undergoing tumour resection several months after SARS-CoV-2 infection.

METHODS AND RESULTS: The severity of several lesions with a major focus on the vascular bed was analysed in 2 tumour-distant lung fragments of 41 cases: 21 SARS-CoV-2 (+) lung tumour (LT) patients and 20 SARS-CoV-2 (-) LT patients. A systematic evaluation of several lesions was carried out by combining their scores into a grade of I-III. Tissue SARS-CoV-2 genomic/subgenomic transcripts were also investigated. Morphological findings were compared with clinical, laboratory and radiological data. SARS-CoV-2 (+) LT patients with previous pneumonia showed more severe parenchymal and vascular lesions than those found in SARS-CoV-2 (+) LT patients without pneumonia and SARS-CoV-2 (-) LT patients, mainly when combined scores were used. SARS-CoV-2 viral transcripts were not detected in any sample. SARS-CoV-2 (+) LT patients with pneumonia showed a significantly higher radiological global injury score. No other associations were found between morphological lesions and clinical data.

CONCLUSIONS: To our knowledge, this is the first study that, after a granular evaluation of tissue parameters, detected several changes in lungs from patients undergoing tumour resection after SARS-CoV-2 infection. These lesions, in particular vascular remodelling, could have an important impact overall on the future management of these frail patients.}, } @article {pmid37102680, year = {2023}, author = {Bradbury, J and Wilkinson, S and Schloss, J}, title = {Nutritional Support During Long COVID: A Systematic Scoping Review.}, journal = {Journal of integrative and complementary medicine}, volume = {29}, number = {11}, pages = {695-704}, doi = {10.1089/jicm.2022.0821}, pmid = {37102680}, issn = {2768-3613}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Sarcopenia ; *COVID-19 ; Vitamins/therapeutic use ; *Malnutrition/prevention & control ; Nutritional Support ; Glutathione ; Anti-Inflammatory Agents ; Inflammation ; }, abstract = {Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID. Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review. Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine. Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions. This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment. Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.}, } @article {pmid37101566, year = {2023}, author = {Sun, L and Chopra, P and Tomris, I and van der Woude, R and Liu, L and de Vries, RP and Boons, GJ}, title = {Well-Defined Heparin Mimetics Can Inhibit Binding of the Trimeric Spike of SARS-CoV-2 in a Length-Dependent Manner.}, journal = {JACS Au}, volume = {3}, number = {4}, pages = {1185-1195}, pmid = {37101566}, issn = {2691-3704}, abstract = {The emergence of new SARS-CoV-2 variants and the dangers of long-covid necessitate the development of broad-acting therapeutics that can reduce viral burden. SARS-CoV-2 employs heparan sulfate (HS) as an initial cellular attachment factor, and therefore, there is interest in developing heparin as a therapeutic for SARS-CoV-2. Its use is, however, complicated by structural heterogeneity and the risk of causing bleeding and thrombocytopenia. Here, we describe the preparation of well-defined heparin mimetics by a controlled head-to-tail assembly of HS oligosaccharides having an alkyne or azide moiety by copper-catalyzed azide-alkyne cycloaddition (CuAAC). Alkyne- and azide-containing sulfated oligosaccharides were prepared from a common precursor by modifying an anomeric linker with 4-pentynoic acid and by enzymatic extension with an N-acetyl-glucosamine having an azide moiety at C-6 (GlcNAc6N3), respectively, followed by CuAAC. The process of enzymatic extension with GlcNAc6N3 followed by CuAAC with the desired alkyne-containing oligosaccharides could be repeated to give compounds composed of 20 and 27 monosaccharides, respectively. The heparin mimetics could inhibit the binding of the SARS-CoV-2 spike or RBD to immobilized heparin or to Vero E6 cells. The inhibitory potency increased with increasing chain length, and a compound composed of four sulfated hexasaccharides linked by triazoles had a similar potency as unfractionated heparin. Sequence analysis and HS microarray binding studies with a wide range of RBDs of variants of concern indicate that they have maintained HS-binding capabilities and selectivities. The heparin mimetics exhibit no or reduced binding to antithrombin-III and platelet factor 4, respectively, which are associated with side effects.}, } @article {pmid37100745, year = {2023}, author = {Cannata, F and Pinto, G and Chiarito, M and Maurina, M and Condello, F and Bombace, S and Villaschi, A and Novelli, L and Stankowski, K and Liccardo, G and Gasparini, G and Donia, D and Celata, A and My, I and Kallikourdis, M and Figliozzi, S and Mantovani, R and Fazzari, F and Bragato, RM and Condorelli, G and Stefanini, GG}, title = {Long-term prognostic impact of subclinical myocardial dysfunction in patients recovered from COVID-19.}, journal = {Echocardiography (Mount Kisco, N.Y.)}, volume = {40}, number = {6}, pages = {464-474}, doi = {10.1111/echo.15575}, pmid = {37100745}, issn = {1540-8175}, support = {//COVID-19 from Regione Lombardia Welfare/ ; }, mesh = {Humans ; Risk Factors ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Predictive Value of Tests ; SARS-CoV-2 ; Prognosis ; *Ventricular Dysfunction, Left/complications ; }, abstract = {BACKGROUND: Cardiovascular sequelae may occur in patients recovered from coronavirus disease 2019 (COVID-19). Recent studies have detected a considerable incidence of subclinical myocardial dysfunction-assessed with speckle-tracking echocardiography-and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia.

METHODS: We prospectively followed up 110 patients hospitalized at our institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 7-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization, and all-cause mortality.

RESULTS: A subclinical myocardial dysfunction-defined as an impairment of left ventricular global longitudinal strain (≥-18%)-was identified at a 7-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (area under the curve: .73) and resulted in a strong independent predictor of extended MACE in multivariate regression analyses. Long-COVID condition was not associated with a worse long-term prognosis, instead.

CONCLUSIONS: In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one-third of the whole population at 7-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimize the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has no prognostic relevance.}, } @article {pmid37100668, year = {2023}, author = {Becerra-García, JA and Sánchez-Gutiérrez, T}, title = {Long-COVID psychological symptoms in child and adolescent population: A standardized proposal for its exploration.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {41}, number = {6}, pages = {384-385}, pmid = {37100668}, issn = {2529-993X}, mesh = {Humans ; Adolescent ; Child ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Surveys and Questionnaires ; }, } @article {pmid37099589, year = {2023}, author = {Dinis Teixeira, JP and Santos, MJDS and Soares, P and Azevedo, L and Barbosa, P and Boas, AV and Cordeiro, JV and Dias, S and Fonseca, M and Goes, AR and Lobão, MJ and Moniz, M and Nóbrega, S and Peralta-Santos, A and Ramos, V and Rocha, JV and da Silva, AC and Brazão, MDL and Leite, A and Nunes, C}, title = {LOCUS (LOng Covid-Understanding Symptoms, events and use of services in Portugal): A three-component study protocol.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0285051}, pmid = {37099589}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Portugal/epidemiology ; Risk Factors ; }, abstract = {Approximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC's burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The "Cardiovascular and respiratory events following COVID-19" component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The "Physical and mental symptoms following COVID-19" component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.}, } @article {pmid37099534, year = {2023}, author = {Knight, RL and Mackintosh, KA and Hudson, J and Shelley, J and Saynor, ZL and McNarry, MA}, title = {Battling the unknown: Using composite vignettes to portray lived experiences of COVID-19 and long-COVID.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0284710}, pmid = {37099534}, issn = {1932-6203}, mesh = {Adult ; Female ; Humans ; Adolescent ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; }, abstract = {Understanding the day-to-day lived experiences of individuals who have had or are still recovering from Coronavirus Disease-19 (COVID-19), whilst a complex challenge, presents the opportunity to listen and learn. Composite vignettes provide a novel approach to explore and present descriptive portrayals of the most commonly derived experiences and recovery journeys. The thematic analysis of 47 shared accounts (semi-structured interviews with adults aged ≥18 years; 40 females; 6-11 months post-COVID-19 infection) produced a series of four intricate character stories written through the lens of a single individual. Each vignette gives a voice to and captures a different experience trajectory. From the point of initial symptom development onwards, the vignettes depict how COVID-19 has affected everyday lives, focusing on the secondary non-biological socio-psychological effects and implications. The vignettes highlight in participants' own words: i) the potential negative implications of not addressing the psychological effects of COVID-19; ii) the lack of symptom and recovery linearity; iii) the ongoing 'lottery' of access to healthcare services; and iv) the highly variable, yet generally devastating, impacts that COVID-19 and consequent long-COVID has had across multiple facets of daily living.}, } @article {pmid37099136, year = {2023}, author = {Gvinjilia, L and Baliashvili, D and Shadaker, S and Averhoff, F and Kandelaki, L and Kereselidze, M and Tsertsvadze, T and Chkhartishvili, N and Butsashvili, M and Metreveli, D and Gamkrelidze, A and Armstrong, PA}, title = {Impact of Hepatitis C Virus Infection and Treatment on Mortality in the Country of Georgia, 2015-2020.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {3}, pages = {405-413}, pmid = {37099136}, issn = {1537-6591}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Humans ; Hepacivirus ; Antiviral Agents/therapeutic use ; Cohort Studies ; Georgia/epidemiology ; *Hepatitis C/drug therapy/epidemiology ; *Hepatitis C, Chronic/drug therapy ; }, abstract = {BACKGROUND: Mortality related to hepatitis C virus (HCV) infection is a key indicator for elimination. We assessed the impact of HCV infection and treatment on mortality in the country of Georgia during 2015-2020.

METHODS: We conducted a population-based cohort study using data from Georgia's national HCV Elimination Program and death registry. We calculated all-cause mortality rates in 6 cohorts: (1) Negative for anti-HCV; (2) anti-HCV positive, unknown viremia status; (3) current HCV infection and untreated; (4) discontinued treatment; (5) completed treatment, no sustained virologic response (SVR) assessment; (6) completed treatment and achieved SVR. Cox proportional hazards models were used to calculate adjusted hazards ratios and confidence intervals. We calculated the cause-specific mortality rates attributable to liver-related causes.

RESULTS: After a median follow-up of 743 days, 100 371 (5.7%) of 1 764 324 study participants died. The highest mortality rate was observed among HCV infected patients who discontinued treatment (10.62 deaths per 100 PY, 95% confidence interval [CI]: 9.65, 11.68), and untreated group (10.33 deaths per 100 PY, 95% CI: 9.96, 10.71). In adjusted Cox proportional hazards model, the untreated group had almost 6-times higher hazard of death compared to treated groups with or without documented SVR (adjusted hazard ratio [aHR] = 5.56, 95% CI: 4.89, 6.31). Those who achieved SVR had consistently lower liver-related mortality compared to cohorts with current or past exposure to HCV.

CONCLUSIONS: This large population-based cohort study demonstrated the marked beneficial association between hepatitis C treatment and mortality. The high mortality rates observed among HCV infected and untreated persons highlights the need to prioritize linkage to care and treatment to achieve elimination goals.}, } @article {pmid37098838, year = {2023}, author = {Tan, KWA and Koh, D}, title = {Long COVID-Challenges in diagnosis and managing return-to-work.}, journal = {Journal of occupational health}, volume = {65}, number = {1}, pages = {e12401}, pmid = {37098838}, issn = {1348-9585}, mesh = {Humans ; Male ; *COVID-19/diagnosis ; Post-Acute COVID-19 Syndrome ; Return to Work ; *Occupational Health ; Pandemics ; COVID-19 Testing ; }, abstract = {OBJECTIVES: Long COVID may be a public health concern resulting in a hidden toll of the pandemic years later, on workers and their work ability in the workforce. We illustrate the challenges in diagnosing long COVID in a patient, its associated psychological impact on work and how return-to-work can be better managed and supported from an occupational health perspective.

METHODS: An Occupational Health trainee working as a government public health officer experienced persistent fatigue, decreased effort tolerance, and difficulties in concentration after contracting COVID-19. There were unintended psychological effects arising from the functional limitations that were not explained with a proper diagnosis. This was further complicated with a lack of access to occupational health services for return-to-work.

RESULTS: He developed his own rehabilitation plan to improve his physical tolerance. Progressive efforts to build up his physical fitness complemented with workplace adjustments helped to overcome his functional limitations and allowed him to effectively return-to-work.

CONCLUSION: Diagnosing long COVID continues to remain challenging due to a lack of consensus on a definitive diagnostic criterion. This may give rise to unintended mental and psychological impact. Workers with long COVID symptoms can return-to-work, involving a complex individualized approach to the symptoms' impact on work, and workplace adjustments and job modifications available. The psychological toll on the worker must also be addressed. Occupational health professionals are best placed to facilitate these workers in their journey to return-to-work, with multi-disciplinary delivery models providing return to work services.}, } @article {pmid37098111, year = {2023}, author = {Lippi, G and Henry, BM and Favresse, J and Plebani, M}, title = {Addressing standardized definitions of post-COVID and long-COVID.}, journal = {Clinical chemistry and laboratory medicine}, volume = {61}, number = {8}, pages = {1361-1362}, pmid = {37098111}, issn = {1437-4331}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37097045, year = {2023}, author = {Pizzuto, DA and Buonsenso, D and Morello, R and De Rose, C and Valentini, P and Fragano, A and Baldi, F and Di Giuda, D}, title = {Lung perfusion assessment in children with long-COVID: A pilot study.}, journal = {Pediatric pulmonology}, volume = {58}, number = {7}, pages = {2059-2067}, doi = {10.1002/ppul.26432}, pmid = {37097045}, issn = {1099-0496}, support = {//Pfizer/ ; }, mesh = {Female ; Humans ; Child ; Pilot Projects ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Lung/diagnostic imaging ; Tomography, Emission-Computed, Single-Photon/methods ; Perfusion ; }, abstract = {BACKGROUND: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with [99m] Tc-MAA SPECT/CT.

MATERIALS AND METHODS: lung [99m] Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed.

RESULTS: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on [99m] Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT.

CONCLUSIONS: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.}, } @article {pmid37096187, year = {2023}, author = {O'Mahoney, LL and Routen, A and Gillies, C and Ekezie, W and Welford, A and Zhang, A and Karamchandani, U and Simms-Williams, N and Cassambai, S and Ardavani, A and Wilkinson, TJ and Hawthorne, G and Curtis, F and Kingsnorth, AP and Almaqhawi, A and Ward, T and Ayoubkhani, D and Banerjee, A and Calvert, M and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Evans, RA and Zaccardi, F and Wright, S and Khunti, K}, title = {Corrigendum to "The prevalence and long-term health effects of long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis".}, journal = {EClinicalMedicine}, volume = {59}, number = {}, pages = {101959}, pmid = {37096187}, issn = {2589-5370}, abstract = {[This corrects the article DOI: 10.1016/j.eclinm.2022.101762.].}, } @article {pmid37095813, year = {2023}, author = {Kintrilis, N}, title = {Viral Shedding and Persistence of Anosmia and Ageusia in an Asymptomatic SARS-CoV-2 Infection.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36574}, pmid = {37095813}, issn = {2168-8184}, abstract = {The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the region of Wuhan, China is responsible for the ongoing pandemic of coronavirus disease-19 (COVID-19) that has been a part of our life for almost three years now. Although there have been multiple reports of prolonged viral shedding in people with severe disease, viral shedding lasting for extended periods can occur in patients with less serious clinical insults or even asymptomatic individuals. Herein, we report a case of a female patient that, although otherwise asymptomatic, remained positive on nasopharyngeal viral testing for a prolonged period, alongside persisting complaints of anosmia and ageusia. The patient may well have been one of the first individuals to be infected in the Greek territory; we followed up on her long-term COVID sequelae from the time of proof of infection up until the present day.}, } @article {pmid37095536, year = {2023}, author = {Yin, JX and Agbana, YL and Sun, ZS and Fei, SW and Zhao, HQ and Zhou, XN and Chen, JH and Kassegne, K}, title = {Increased interleukin-6 is associated with long COVID-19: a systematic review and meta-analysis.}, journal = {Infectious diseases of poverty}, volume = {12}, number = {1}, pages = {43}, pmid = {37095536}, issn = {2049-9957}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Interleukin-6 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) can involve persistence, sequelae, and other clinical complications that last weeks to months to evolve into long COVID-19. Exploratory studies have suggested that interleukin-6 (IL-6) is related to COVID-19; however, the correlation between IL-6 and long COVID-19 is unknown. We designed a systematic review and meta-analysis to assess the relationship between IL-6 levels and long COVID-19.

METHODS: Databases were systematically searched for articles with data on long COVID-19 and IL-6 levels published before September 2022. A total of 22 published studies were eligible for inclusion following the PRISMA guidelines. Analysis of data was undertaken by using Cochran's Q test and the Higgins I-squared (I[2]) statistic for heterogeneity. Random-effect meta-analyses were conducted to pool the IL-6 levels of long COVID-19 patients and to compare the differences in IL-6 levels among the long COVID-19, healthy, non-postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (non-PASC), and acute COVID-19 populations. The funnel plot and Egger's test were used to assess potential publication bias. Sensitivity analysis was used to test the stability of the results.

RESULTS: An increase in IL-6 levels was observed after SARS-CoV-2 infection. The pooled estimate of IL-6 revealed a mean value of 20.92 pg/ml (95% CI = 9.30-32.54 pg/ml, I[2] = 100%, P < 0.01) for long COVID-19 patients. The forest plot showed high levels of IL-6 for long COVID-19 compared with healthy controls (mean difference = 9.75 pg/ml, 95% CI = 5.75-13.75 pg/ml, I[2] = 100%, P < 0.00001) and PASC category (mean difference = 3.32 pg/ml, 95% CI = 0.22-6.42 pg/ml, I[2] = 88%, P = 0.04). The symmetry of the funnel plots was not obvious, and Egger's test showed that there was no significant small study effect in all groups.

CONCLUSIONS: This study showed that increased IL-6 correlates with long COVID-19. Such an informative revelation suggests IL-6 as a basic determinant to predict long COVID-19 or at least inform on the "early stage" of long COVID-19.}, } @article {pmid37094584, year = {2023}, author = {Abbate, G and De Iulio, B and Thomas, G and Priday, A and Biondi-Zoccai, G and Markley, R and Abbate, A}, title = {Postural Orthostatic Tachycardia Syndrome After COVID-19: A Systematic Review of Therapeutic Interventions.}, journal = {Journal of cardiovascular pharmacology}, volume = {82}, number = {1}, pages = {23-31}, doi = {10.1097/FJC.0000000000001432}, pmid = {37094584}, issn = {1533-4023}, mesh = {Male ; Humans ; Female ; Young Adult ; Adult ; Middle Aged ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology/therapy ; Adrenergic beta-Antagonists/therapeutic use ; *Midodrine/therapeutic use ; Heart Rate ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.}, } @article {pmid37092568, year = {2023}, author = {Holst, AS and Jacques-Aviñó, C and Berenguera, A and Martínez-Bueno, C and Munrós-Feliu, J and Pinzón-Sanabria, D and Valls-Llobet, C and López-Jiménez, T and García-Egea, A and Vicente-Hernández, MM and Medina-Perucha, L}, title = {Menstrual health and management during the COVID-19 syndemic in the Barcelona area (Spain): A qualitative study.}, journal = {Women's health (London, England)}, volume = {19}, number = {}, pages = {17455057231166644}, pmid = {37092568}, issn = {1745-5065}, mesh = {Female ; Humans ; Spain/epidemiology ; *Syndemic ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Communicable Disease Control ; Menstruation ; }, abstract = {BACKGROUND: Available evidence suggests that menstrual health and management have been impaired during the COVID-19 syndemic. However, research in this area is scarce, and it is failing to voice the experiences of women and people who menstruate regarding their menstrual experiences.

OBJECTIVES: This study aimed to explore the experiences of menstrual health and menstrual management among women and people who menstruate in the Barcelona area (Spain) during the COVID-19 syndemic.

DESIGN: This is a qualitative study, conducted taking a critical feminist approach, is embedded in the 'Equity and Menstrual Health in Spain' project.

METHODS: It includes photo-elicitation individual interviews with 34 women and people who menstruate in the area of Barcelona (Spain). Data were collected in person and through telephone calls between December 2020 and February 2021. Analyses were performed using Thematic Analysis.

RESULTS: Main findings navigated through the menstrual changes experienced by some participants, especially women living with long COVID-19, and the barriers to access healthcare and menstrual products during COVID-19. While some participants experienced menstrual poverty, this did not appear to be exacerbated during COVID-19. Instead, access to menstrual products was compromised based on products' availability and mobility restrictions. Menstrual management and self-care were generally easier, given that menstrual experiences were almost exclusively relegated to private spaces during lockdown periods.

CONCLUSIONS: Our findings highlight the need to further research and policy efforts towards promoting menstrual health and equity, considering social determinants of health, and taking intersectional and gender-based approaches. These strategies should be further encouraged in social and health crises such as the COVID-19 syndemic.}, } @article {pmid37091941, year = {2023}, author = {Regunath, H and Goldstein, NM and Guntur, VP}, title = {Long COVID: Where Are We in 2023?.}, journal = {Missouri medicine}, volume = {120}, number = {2}, pages = {102-105}, pmid = {37091941}, issn = {0026-6620}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37091856, year = {2023}, author = {Meftah, E and Rahmati, R and Zari Meidani, F and Khodadadi, S and Chitzan-Zadeh, K and Esfahanian, F and Afshar, S}, title = {Subacute thyroiditis following COVID-19: A systematic review.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1126637}, pmid = {37091856}, issn = {1664-2392}, mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Thyroxine/therapeutic use ; COVID-19 Vaccines/therapeutic use ; *Thyroiditis, Subacute/drug therapy/epidemiology/etiology ; }, abstract = {BACKGROUND: Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19.

METHODS: We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included.

RESULTS: Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine.

CONCLUSION: SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.}, } @article {pmid37091113, year = {2023}, author = {Hecht, LM and Adams, R and Dutkiewicz, D and Radloff, D and Wales, MN and Whitmer, J and Murphy, D and Santarossa, S}, title = {"Healing Can Be a Very Jagged Line": Reflections on Life as a COVID-19 Long Hauler.}, journal = {Journal of patient-centered research and reviews}, volume = {10}, number = {2}, pages = {77-81}, pmid = {37091113}, issn = {2330-0698}, abstract = {"Long COVID" - a term referring to COVID-19-associated symptoms and conditions (ie, sequelae) that remain or emerge after resolution of a SARS-CoV-2 infection - is a multifaceted condition about which little is known. As part of formalized patient-engaged research at a large Midwestern health system, patient stakeholders with long COVID (N=5) wrote stories based on their lived experience, as this was their preferred format for detailing their experience with the condition. These patient stakeholders reviewed one another's stories, identified relevant quotes, and provided opportunities for elaboration. Independently, a trained researcher extracted quotes from the stories, identified themes, and wove the quotes together to share the independent, yet similar, stories. Emergent themes were that of uncertainty about the symptomatology of long COVID and its effects on patients' mental health, physical functioning, family unit, self-identity, and future outlook. Further patient-engaged research on understanding the lived experience of long COVID may serve to advance knowledge and treatment. Health care providers caring for those with long COVID can benefit from listening and validating the stories of individuals suffering from this condition.}, } @article {pmid37090748, year = {2023}, author = {Cvetko, TT and Ljubic, J and Ostricki, B}, title = {Purulent pericarditis caused by methicillin-sensitive Staphylococcus aureus in an immunocompetent adult after COVID-19 pneumonia: a case report.}, journal = {European heart journal. Case reports}, volume = {7}, number = {4}, pages = {ytad141}, pmid = {37090748}, issn = {2514-2119}, abstract = {BACKGROUND: SARS-CoV-2 has been implicated in many cardiac pathologies, manifesting mainly as acute. However, acute purulent pericarditis is exceedingly rare in the antibiotic era. Though, few studies have associated it with long-COVID, prompt recognition and treatment are crucial.

CASE SUMMARY: A 61-year-old immunocompetent woman presented with a left lower limb pitting oedema 1 month after COVID-19 pneumonia. Following clinical, laboratory, and imaging work-up, the patient was found to have deep vein thrombosis of the anterior and posterior tibial and gastrocnemius veins. Owning to persistent sinus tachycardia, an additional work-up was performed, which revealed a large pericardial effusion. Pericardiocentesis drained the frank pus, and subsequently, empirical antibiotics therapy was initiated. Pericardial fluid cultures showed methicillin-sensitive Staphylococcus aureus (MSSA). Following the antibiotic treatment with cloxacillin 6 × 2 g IV for 6 weeks, the patient fully recovered.

DISCUSSION: Herein, we report a rare case of bacterial pericarditis caused by MSSA 1 month after COVID-19 pneumonia. Additionally, this condition may arise as a result of immunosuppressive treatment with glucocorticoids during and after COVID-19 pneumonia. However, the causal association has not yet been confirmed.}, } @article {pmid37090595, year = {2023}, author = {Visvabharathy, L and Zhu, C and Orban, ZS and Yarnoff, K and Palacio, N and Jimenez, M and Lim, PH and Penaloza-MacMaster, P and Koralnik, IJ}, title = {Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37090595}, support = {DP2 DA051912/DA/NIDA NIH HHS/United States ; R01 AG059291/AG/NIA NIH HHS/United States ; U54 EB027049/EB/NIBIB NIH HHS/United States ; }, abstract = {Long COVID patients who experienced severe acute SARS-CoV-2 infection can present with humoral autoimmunity. However, whether mild SARS-CoV-2 infection increases autoantibody responses and whether vaccination can decrease autoimmunity in long COVID patients is unknown. Here, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with systemic lupus erythematosus (SLE) and inflammatory myopathies in long COVID patients with persistent neurologic symptoms to a greater extent than COVID convalescent controls at 8 months post-infection. Furthermore, high titers of SLE-associated autoantibodies in long COVID patients are associated with impaired cognitive performance and greater symptom severity, and subsequent vaccination/booster does not decrease autoantibody titers. In summary, we found that mild SARS-CoV-2 infection can induce persistent humoral autoimmunity in both long COVID patients and healthy COVID convalescents, suggesting that a reappraisal of vaccination and mitigation strategies is warranted.}, } @article {pmid37090451, year = {2023}, author = {Nehme, A and Barakat, M and Malaeb, D and Obeid, S and Hallit, S and Haddad, G}, title = {Association between COVID-19 symptoms, COVID-19 vaccine, and somatization among a sample of the Lebanese adults.}, journal = {Pharmacy practice}, volume = {21}, number = {1}, pages = {2763}, pmid = {37090451}, issn = {1885-642X}, abstract = {OBJECTIVES: Long COVID syndrome, the poorly defined illness, has been increasingly mentioned in recent studies yet is still poorly understood especially when it comes to precipitating and modulating factors, the high prevalence of mental health problems associated with the COVID-19 pandemic has brought to light the hypothesis of the existence of a psychological component associated with the persistence of symptoms and if vaccination may serve as a modulating factor. This study aims to examine the prevalence of somatization disorders and association between persistent COVID-19 symptoms and COVID-19 vaccine with somatization among a sample of the Lebanese general population.

METHODS: A cross-sectional study was carried out between September and October 2021. The snowball sampling technique was picked to choose a sample that addressed all Lebanese Mohafazat. Patient Health Questionnaire-15 (PHQ-15) was used to assess somatization.

RESULTS: A total of 403 participants was enrolled in this study, with a mean age of 32.76 ± 13.24 years, 108 (26.8%) had medium somatization symptoms (PHQ-15 scores ≥10). Having persistent COVID symptoms (β=2.15) was significantly associated with more somatization, whereas the intake of COVID vaccine (β=-1.17) was significantly associated with less somatization.

CONCLUSION: Long lasting COVID-19 symptoms were closely related to somatization, although the administration of the COVID-19 vaccine was associated with less somatization. However, further studies are needed to provide a better understanding of the relationship between long COVID and somatization, on one hand, and the modulating factors on the other hand.}, } @article {pmid37090348, year = {2023}, author = {Al-Qahtani, ZA and Al Jabbar, I and Alhadi, W and Alahmari, SA and Alqahtani, RM and Alnujaymi, BM and Al-Qahtani, RA}, title = {Memory, Attention, and Concentration Dysfunction Post-COVID-19 Among College Students in Saudi Arabia: A Case-Control Study.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36419}, pmid = {37090348}, issn = {2168-8184}, abstract = {Introduction Multiple studies have demonstrated the multi-systemic involvement of COVID-19, and among all of these systems, there is mounting evidence that COVID-19 is linked to neurocognitive impairment, particularly when neurological symptoms are present. Our aim is to study the concept of cognitive dysfunction post-COVID-19 among college students in Saudi Arabia and its potential effect on their academic performance. Methods A population-based, observational case-control study was conducted across the Kingdom of Saudi Arabia, from May 2022 to September 2022. A total of 2,150 eligible students have completed the study questionnaire. An exact 776 (36.1%) of them had COVID-19 infection (group 1), while 1,374 (63.9%) students had not (group 2). The sample population was college-enrolled students from 18 to 28 years old, with a mean age of 21.3 for group 1 and 20.8 for group 2. Both groups were handed the same data collection tool to establish whether the COVID-19 survivors had cognitive deficits more than the control group. Results There was no significant difference between the two groups regarding their bio-demographic data, study methods, or vaccination rate. However, both Neurological Fatigue and Big Five Inventory score were significantly higher among infected students, comparable to non-infected students. A negative relation was found between the infected students' neurological fatigue (rho=-0.14), cognitive failure (rho=-0.10), and depression and anxiety scale with their GPA (rho=0.03). Contrarily, infected students showed a positive relationship between their GPA and the Big Five Inventory (rho=0.13) and Short Grit Scale (rho=0.14). Also, there was a significant inverse relation between students' apathy motivation with their Big Five Inventory. Likewise, there was an inverse relation between their neurological fatigue, cognitive failure, and apathy motivation with their Short Grit Scale. Conclusion We demonstrated that college students who have survived COVID-19 infection mostly complain of cognitive impairment, even though most of them have no comorbidities or psychological disorders.}, } @article {pmid37089610, year = {2023}, author = {Plaut, S}, title = {"Long COVID-19" and viral "fibromyalgia-ness": Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia).}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {952278}, pmid = {37089610}, issn = {2296-858X}, abstract = {The coronavirus pandemic has led to a wave of chronic disease cases; "Long COVID-19" is recognized as a new medical entity and resembles "fibromyalgia" which, likewise, lacks a clear mechanism. Observational studies indicate that up to 30%-40% of convalescent COVID-19 patients develop chronic widespread pain and fatigue and fulfill the 2016 diagnostic criteria for "fibromyalgia." A recent study suggested a theoretical neuro-biomechanical model (coined "Fascial Armoring") to help explain the pathogenesis and cellular pathway of fibromyalgia, pointing toward mechanical abnormalities in connective tissue and fascia, driven by contractile myo/fibroblasts and altered extracellular matrix remodeling with downstream corresponding neurophysiological aberrations. This may help explain several of fibromyalgia's manifestations such as pain, distribution of pain, trigger points/tender spots, hyperalgesia, chronic fatigue, cardiovascular abnormalities, metabolic abnormalities, autonomic abnormalities, small fiber neuropathy, various psychosomatic symptoms, lack of obvious inflammation, and silent imaging investigations. Pro-inflammatory and pro-fibrotic pathways provide input into this mechanism via stimulation of proto/myofibroblasts. In this hypothesis and theory paper the theoretical model of Fascial Armoring is presented to help explain the pathogenesis and manifestations of "long COVID-19" as a disease of immuno-rheumo-psycho-neurology. The model is also used to make testable experimental predictions on investigations and predict risk and relieving factors.}, } @article {pmid37089476, year = {2023}, author = {Kisielinski, K and Hirsch, O and Wagner, S and Wojtasik, B and Funken, S and Klosterhalfen, B and Kanti Manna, S and Prescher, A and Sukul, P and Sönnichsen, A}, title = {Physio-metabolic and clinical consequences of wearing face masks-Systematic review with meta-analysis and comprehensive evaluation.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1125150}, pmid = {37089476}, issn = {2296-2565}, mesh = {Humans ; Young Adult ; Adult ; Middle Aged ; *COVID-19/epidemiology ; Masks ; SARS-CoV-2 ; Pandemics ; Carbon Dioxide ; Post-Acute COVID-19 Syndrome ; *Respiratory Protective Devices ; Dyspnea ; }, abstract = {BACKGROUND: As face masks became mandatory in most countries during the COVID-19 pandemic, adverse effects require substantiated investigation.

METHODS: A systematic review of 2,168 studies on adverse medical mask effects yielded 54 publications for synthesis and 37 studies for meta-analysis (on n = 8,641, m = 2,482, f = 6,159, age = 34.8 ± 12.5). The median trial duration was only 18 min (IQR = 50) for our comprehensive evaluation of mask induced physio-metabolic and clinical outcomes.

RESULTS: We found significant effects in both medical surgical and N95 masks, with a greater impact of the second. These effects included decreased SpO2 (overall Standard Mean Difference, SMD = -0.24, 95% CI = -0.38 to -0.11, p < 0.001) and minute ventilation (SMD = -0.72, 95% CI = -0.99 to -0.46, p < 0.001), simultaneous increased in blood-CO2 (SMD = +0.64, 95% CI = 0.31-0.96, p < 0.001), heart rate (N95: SMD = +0.22, 95% CI = 0.03-0.41, p = 0.02), systolic blood pressure (surgical: SMD = +0.21, 95% CI = 0.03-0.39, p = 0.02), skin temperature (overall SMD = +0.80 95% CI = 0.23-1.38, p = 0.006) and humidity (SMD +2.24, 95% CI = 1.32-3.17, p < 0.001). Effects on exertion (overall SMD = +0.9, surgical = +0.63, N95 = +1.19), discomfort (SMD = +1.16), dyspnoea (SMD = +1.46), heat (SMD = +0.70), and humidity (SMD = +0.9) were significant in n = 373 with a robust relationship to mask wearing (p < 0.006 to p < 0.001). Pooled symptom prevalence (n = 8,128) was significant for: headache (62%, p < 0.001), acne (38%, p < 0.001), skin irritation (36%, p < 0.001), dyspnoea (33%, p < 0.001), heat (26%, p < 0.001), itching (26%, p < 0.001), voice disorder (23%, p < 0.03), and dizziness (5%, p = 0.01).

DISCUSSION: Masks interfered with O2-uptake and CO2-release and compromised respiratory compensation. Though evaluated wearing durations are shorter than daily/prolonged use, outcomes independently validate mask-induced exhaustion-syndrome (MIES) and down-stream physio-metabolic disfunctions. MIES can have long-term clinical consequences, especially for vulnerable groups. So far, several mask related symptoms may have been misinterpreted as long COVID-19 symptoms. In any case, the possible MIES contrasts with the WHO definition of health.

CONCLUSION: Face mask side-effects must be assessed (risk-benefit) against the available evidence of their effectiveness against viral transmissions. In the absence of strong empirical evidence of effectiveness, mask wearing should not be mandated let alone enforced by law.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021256694, identifier: PROSPERO 2021 CRD42021256694.}, } @article {pmid37088245, year = {2023}, author = {Sallis, JF and Adlakha, D and Oyeyemi, A and Salvo, D}, title = {Public health research on physical activity and COVID-19: Progress and updated priorities.}, journal = {Journal of sport and health science}, volume = {12}, number = {5}, pages = {553-556}, pmid = {37088245}, issn = {2213-2961}, support = {P30 DK092950/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Public Health ; Exercise ; }, abstract = {• Research produced during the pandemic showed pre-diagnosis physical activity was associated with substantially lower risk of severe coronavirus disease 2019 (COVID-19) outcomes. • Pandemic restrictions on common places for physical activity were associated with decreased physical activity and increased sedentary behavior. • There were few studies of interventions to increase physical activity during the pandemic, the role of physical activity in COVID-19 inequities, and built environment contributions to COVID-19 outcomes. • Emerging research priorities include physical activity and long COVID and physical activity as a vaccine adjuvant. • Except for recommendations from the World Health Organization, physical activity was widely ignored in public health guidance.}, } @article {pmid37087772, year = {2023}, author = {Rivera, R and Amudio, C and Cruz, JP and Brunetti, E and Catalan, P and Sordo, JG and Echeverria, D and Badilla, L and Chamorro, A and Gonzalez, C and Ojeda, H and Rodriguez, C and Rogers, N and Bravo, L and Bravo, F and Carrasco, A and Gonzalez, W and Lopez, S and Orellana, ML and Oportus, M and Salazar, A and Palacios, G and Nguyen, PT}, title = {The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.}, journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association}, volume = {32}, number = {6}, pages = {107138}, pmid = {37087772}, issn = {1532-8511}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Brain Ischemia/therapy ; Thrombectomy/adverse effects/methods ; Retrospective Studies ; *COVID-19/epidemiology ; Pandemics ; Public Health ; Treatment Outcome ; *Stroke/diagnosis/therapy/epidemiology ; }, abstract = {OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile.

MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program.

RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters.

CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.}, } @article {pmid37087708, year = {2023}, author = {Heitmann, J and Kreutz, J and Aldudak, S and Schieffer, E and Schieffer, B and Schäfer, AC}, title = {A practical approach for the treatment of post-COVID symptoms.}, journal = {Herz}, volume = {48}, number = {3}, pages = {243-246}, pmid = {37087708}, issn = {1615-6692}, mesh = {Humans ; Female ; *COVID-19/therapy ; SARS-CoV-2 ; Heparin/therapeutic use ; Pandemics ; }, abstract = {For the past 3 years, our daily lives have been largely dictated by the coronavirus disease 2019 (COVID-19) pandemic. In many people, this infectious disease leads to long-lasting symptoms, which can vary greatly in form and intensity between individuals. This report describes the case of a young patient who had no health restrictions until she came into contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As part of a post-COVID syndrome, she not only temporarily lost her ability to work, but was also no longer able to manage her daily life independently. A crucial therapeutic approach, in this case, was the use of heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.) apheresis.}, } @article {pmid37087365, year = {2023}, author = {Vandersteen, C and Dubrulle, C and Manera, V and Castillo, L and Payne, M and Gros, A}, title = {Persistent post-COVID-19 dysosmia: Practices survey of members of the French National Union of Otorhinolaryngology-Head and Neck Surgery Specialists. CROSS analysis.}, journal = {European annals of otorhinolaryngology, head and neck diseases}, volume = {140}, number = {4}, pages = {159-163}, pmid = {37087365}, issn = {1879-730X}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Olfaction Disorders/etiology/therapy/diagnosis ; *Otolaryngology ; Adrenal Cortex Hormones/therapeutic use ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Persistent dysosmia more than 3 months after SARS-CoV-2 disease (COVID-19) is considered as long-COVID olfactory disease (LCOD). The primary objective of this study was to evaluate the diagnostic and therapeutic management of LCOD in the daily clinical practice of members of the National Union of Otorhinolaryngology-Head and Neck Surgery Specialists (Syndicat national des médecins spécialisés en ORL et chirurgie cervico-faciale) (SNORL). The secondary objective was to identify factors influencing management within the descriptive survey data.

MATERIALS AND METHODS: A questionnaire was designed (GoogleForm®) and e-mailed to all 715 SNORL members in January 2022.

RESULTS: The response rate was 7.4% (n=53/715). In total, 94.3% of respondents (n=50) had managed LCOD cases, and 56% (n=28) used psychophysical olfactory tests. Specific olfactory medical therapy involved local corticosteroid nasal sprays in 49.1% of cases (n=26) and oral corticosteroids in 32.1% (n=17). Olfactory self-training was prescribed by 81.1% of respondents, with associated speech pathologist therapy in 15.1% (n=8) of cases. No predictive factors for specific management were identified.

CONCLUSION: Olfactometry is currently under-applied. Consistent with guidelines, non-drug therapy (olfactory training) is the first-line treatment for LCOD.}, } @article {pmid37084750, year = {2023}, author = {Piechotta, V and Siemens, W and Thielemann, I and Toews, M and Koch, J and Vygen-Bonnet, S and Kothari, K and Grummich, K and Braun, C and Kapp, P and Labonté, V and Wichmann, O and Meerpohl, JJ and Harder, T}, title = {Safety and effectiveness of vaccines against COVID-19 in children aged 5-11 years: a systematic review and meta-analysis.}, journal = {The Lancet. Child & adolescent health}, volume = {7}, number = {6}, pages = {379-391}, pmid = {37084750}, issn = {2352-4650}, mesh = {COVID-19 Vaccines/adverse effects ; mRNA Vaccines ; Systemic Inflammatory Response Syndrome ; Child ; *Myocarditis ; *Vaccines ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control/complications ; BNT162 Vaccine ; SARS-CoV-2 ; }, abstract = {BACKGROUND: To date, more than 761 million confirmed SARS-CoV-2 infections have been recorded globally, and more than half of all children are estimated to be seropositive. Despite high SARS-CoV-2 infection incidences, the rate of severe COVID-19 in children is low. We aimed to assess the safety and efficacy or effectiveness of COVID-19 vaccines approved in the EU for children aged 5-11 years.

METHODS: In this systematic review and meta-analysis, we included studies of any design identified through searching the COVID-19 L·OVE (living overview of evidence) platform up to Jan 23, 2023. We included studies with participants aged 5-11 years, with any COVID-19 vaccine approved by the European Medicines Agency-ie, mRNA vaccines BNT162b2 (Pfizer-BioNTech), BNT162b2 Bivalent (against original strain and omicron [BA.4 or BA.5]), mRNA-1273 (Moderna), or mRNA-1273.214 (against original strain and omicron BA.1). Efficacy and effectiveness outcomes were SARS-CoV-2 infection (PCR-confirmed or antigen-test confirmed), symptomatic COVID-19, hospital admission due to COVID-19, COVID-19-related mortality, multisystem inflammatory syndrome in children (MIS-C), and long-term effects of COVID-19 (long COVID or post-COVID-19 condition as defined by study investigators or per WHO definition). Safety outcomes of interest were serious adverse events, adverse events of special interest (eg, myocarditis), solicited local and systemic events, and unsolicited adverse events. We assessed risk of bias and rated the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluation approach. This study was prospectively registered with PROSPERO, CRD42022306822.

FINDINGS: Of 5272 screened records, we included 51 (1·0%) studies (n=17 [33%] in quantitative synthesis). Vaccine effectiveness after two doses against omicron infections was 41·6% (95% CI 28·1-52·6; eight non-randomised studies of interventions [NRSIs]; CoE low), 36·2% (21·5-48·2; six NRSIs; CoE low) against symptomatic COVID-19, 75·3% (68·0-81·0; six NRSIs; CoE moderate) against COVID-19-related hospitalisations, and 78% (48-90, one NRSI; CoE very low) against MIS-C. Vaccine effectiveness against COVID-19-related mortality was not estimable. Crude event rates for deaths in unvaccinated children were less than one case per 100 000 children, and no events were reported for vaccinated children (four NRSIs; CoE low). No study on vaccine effectiveness against long-term effects was identified. Vaccine effectiveness after three doses was 55% (50-60; one NRSI; CoE moderate) against omicron infections, and 61% (55-67; one NRSI; CoE moderate) against symptomatic COVID-19. No study reported vaccine efficacy or effectiveness against hospitalisation following a third dose. Safety data suggested no increased risk of serious adverse events (risk ratio [RR] 0·83 [95% CI 0·21-3·33]; two randomised controlled trials; CoE low), with approximately 0·23-1·2 events per 100 000 administered vaccines reported in real-life observations. Evidence on the risk of myocarditis was uncertain (RR 4·6 [0·1-156·1]; one NRSI; CoE low), with 0·13-1·04 observed events per 100 000 administered vaccines. The risk of solicited local reactions was 2·07 (1·80-2·39; two RCTs; CoE moderate) after one dose and 2·06 (1·70-2·49; two RCTs; CoE moderate) after two doses. The risk of solicited systemic reactions was 1·09 (1·04-1·16; two RCTs; CoE moderate) after one dose and 1·49 (1·34-1·65; two RCTs; CoE moderate) after two doses. The risk of unsolicited adverse events after two doses (RR 1·21 [1·07-1·38]; CoE moderate) was higher among mRNA-vaccinated compared with unvaccinated children.

INTERPRETATION: In children aged 5-11 years, mRNA vaccines are moderately effective against infections with the omicron variant, but probably protect well against COVID-19 hospitalisations. Vaccines were reactogenic but probably safe. Findings of this systematic review can serve as a basis for public health policy and individual decision making on COVID-19 vaccination in children aged 5-11 years.

FUNDING: German Federal Joint Committee.}, } @article {pmid37083203, year = {2023}, author = {Iovine, E and Di Mattia, G and Nenna, R and La Regina, DP and Mancino, E and Petrarca, L and Conti, MG and Matera, L and Virgili, F and Midulla, F and , }, title = {Lung function after SARS-CoV-2 infection: A prospective cohort study in children.}, journal = {Pediatric pulmonology}, volume = {58}, number = {7}, pages = {2009-2016}, doi = {10.1002/ppul.26425}, pmid = {37083203}, issn = {1099-0496}, mesh = {Adult ; Child ; Humans ; Prospective Studies ; *COVID-19/complications ; SARS-CoV-2 ; Vital Capacity ; Forced Expiratory Volume ; Spirometry/methods ; Lung ; }, abstract = {INTRODUCTION: Although impaired lung function after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been described in adults, it is unclear whether lung function might be altered in children, especially among asymptomatic or mildly symptomatic patients. In this study, we report the results of lung function testing performed after SARS-CoV-2 infection in a large pediatric population.

METHODS: The study included 589 patients with previous confirmed SARS-CoV-2 infection aged 0-18 years. Both symptomatic and asymptomatic patients during acute infection were enrolled in the study. A spirometry was performed in all cooperating patients.

RESULTS: The mean age of enrolled patients was 9.6 years and the mean time from infection to enrollment was 171 days. Spirometry was performed and deemed evaluable in 433 patients. No patient had reduced forced vital capacity (FVC) and only 14 patients (3.2%) had a forced expiratory volume in the First second (FEV1) < 80%. The mean spirometry values recorded were in the normal range. There were no statistically significant differences in spirometry values between patients with respiratory symptoms during infection and those without. Similarly, there were no differences in spirometry parameters according to the time elapsed between infection and enrollment.

CONCLUSION: Lung function, according to spirometry values, does not appear to be impaired long after infection in the pediatric population. The presence of respiratory symptoms during SARS-CoV-2 infection would not represent a risk factor for impaired lung function in this cohort of patients.}, } @article {pmid37082741, year = {2023}, author = {Thomas-Purcell, K and Davenport, R and Ayala, V and Purcell, D and Ownby, RL}, title = {Chronic Disease Self-Management of Post-Acute Sequelae of COVID-19 Among Older Adults: A Mixed-Methods Analysis.}, journal = {Clinical interventions in aging}, volume = {18}, number = {}, pages = {607-617}, pmid = {37082741}, issn = {1178-1998}, mesh = {Adult ; Aged ; Humans ; Middle Aged ; Chronic Disease/epidemiology/psychology/therapy ; *COVID-19/complications/epidemiology ; Disease Progression ; Fatigue/etiology ; *Post-Acute COVID-19 Syndrome/epidemiology/psychology/therapy ; Quality of Life ; SARS-CoV-2 ; *Self-Management/methods ; Comorbidity ; }, abstract = {INTRODUCTION: Approximately 20-30% of individuals who contract acute coronavirus disease (COVID-19) infection develop longer term complications of their initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). PASC is characterized by chronic, varying symptomatology.

METHODS: Using a mixed methods study design, we aimed to gain insight into individuals' experience with PASC, including cognitive issues, fatigue, and sleep disturbances. We explored whether our previously developed application (app), aimed at improving self-management skills among individuals with chronic diseases, is relevant for individuals with PASC and gained information to adapt the app for individuals with PASC. The study included 19 individuals, aged 40 years and older, recruited from our research participant database, Nova Southeastern University clinics, and community locations. We included this age range because older adults are more likely to have comorbid conditions, allowing us to better understand the impact of COVID-19 infection in these individuals. Participants completed seven standardized self-report questionnaires online, and an individual semi-structured interview via videoconferencing. Quantitative data were assessed using descriptive statistics and calculating individuals' scores in relation to norms. Qualitative data were analyzed using a thematic analysis approach. Triangulation of the data was accomplished by calculating correlations between participants' responses on self-report scales and themes found in semi-structured interviews.

RESULTS: Themes included disruption of everyday life, diverse physical symptoms, and cognitive problems including brain fog, fatigue, coping, and emotional upset. Quantitative analysis demonstrated that participants experienced high levels of fatigue, negative mood, cognitive problems, and overall reduction in health-related quality of life (HRQOL). Correlation analyses revealed that individual interview responses were related to participants' self-report of symptoms on standard questionnaires.

DISCUSSION: Findings indicate that self-report questionnaires may reflect the experience of individuals with PASC and its impact. Additionally, further efforts to expand our prior mobile app are warranted among individuals with PASC.}, } @article {pmid37081255, year = {2023}, author = {Mungmunpuntipantip, R and Wiwanitkit, V}, title = {Long COVID in Children up to 12 y of Age - A Retrospective Telephonic Survey: Correspondence.}, journal = {Indian journal of pediatrics}, volume = {90}, number = {8}, pages = {843}, pmid = {37081255}, issn = {0973-7693}, mesh = {Humans ; Child ; *Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *COVID-19 ; Surveys and Questionnaires ; }, } @article {pmid37080828, year = {2023}, author = {Turner, S and Khan, MA and Putrino, D and Woodcock, A and Kell, DB and Pretorius, E}, title = {Long COVID: pathophysiological factors and abnormalities of coagulation.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {34}, number = {6}, pages = {321-344}, pmid = {37080828}, issn = {1879-3061}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Inflammation ; *Thrombosis ; }, abstract = {Acute COVID-19 infection is followed by prolonged symptoms in approximately one in ten cases: known as Long COVID. The disease affects ~65 million individuals worldwide. Many pathophysiological processes appear to underlie Long COVID, including viral factors (persistence, reactivation, and bacteriophagic action of SARS CoV-2); host factors (chronic inflammation, metabolic and endocrine dysregulation, immune dysregulation, and autoimmunity); and downstream impacts (tissue damage from the initial infection, tissue hypoxia, host dysbiosis, and autonomic nervous system dysfunction). These mechanisms culminate in the long-term persistence of the disorder characterized by a thrombotic endothelialitis, endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots. These abnormalities of blood vessels and coagulation affect every organ system and represent a unifying pathway for the various symptoms of Long COVID.}, } @article {pmid37080731, year = {2024}, author = {Wacks, M and Wortley, E and Gregorowski, A and Segal, TY and Whittaker, E}, title = {Fifteen-minute consultation: Managing post-COVID-19 syndrome (long COVID) in children and young people.}, journal = {Archives of disease in childhood. Education and practice edition}, volume = {109}, number = {1}, pages = {29-34}, doi = {10.1136/archdischild-2022-324950}, pmid = {37080731}, issn = {1743-0593}, mesh = {Child ; Humans ; Adolescent ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Mental Health ; Referral and Consultation ; Physical Examination ; }, abstract = {Post-COVID-19 syndrome is a new condition that can have a major impact on the physical and mental well-being of children and young people, affecting their ability to access activities including education. Paediatricians and general practitioners need to be able to assess and manage patients with this condition; making the diagnosis, excluding serious pathology, managing comorbidities and accessing appropriate management are crucial. This 15 minute consultation presents an approach to history taking, examination, investigations, management principles and referrals.}, } @article {pmid37080574, year = {2023}, author = {de Jong, CMM and Visser, C and Bemelmans, RHH and Boersma, WG and van den Borst, B and Burggraaf, JLI and Cannegieter, SC and Ten Cate-Hoek, AJ and Croles, FN and Faber, HJ and Faber, LM and Hellemons, ME and Hessels, LM and Huisman, MV and Kamphuisen, PW and Koster, SCE and Kroft, LJM and van der Lee, I and Leentjens, J and Meijer, K and Ninaber, MK and Sondermeijer, BM and Stads, S and Vonk Noordegraaf, A and Winckers, K and Kruip, MJHA and Klok, FA and , }, title = {Chronic thromboembolic pulmonary hypertension and clot resolution after COVID-19-associated pulmonary embolism.}, journal = {The European respiratory journal}, volume = {61}, number = {4}, pages = {}, pmid = {37080574}, issn = {1399-3003}, mesh = {Humans ; *Hypertension, Pulmonary/complications ; *COVID-19/complications ; *Thrombosis ; *Pulmonary Embolism/complications ; Chronic Disease ; }, abstract = {The results of this study suggest that CTEPH is not a more common long-term complication after COVID-19-associated PE than after PE in non-COVID-19 patients, and thrombus resolution did not seem to be different from non-COVID-19-associated PE https://bit.ly/3IjvWL3}, } @article {pmid37080570, year = {2023}, author = {de Jong, CMM and Le, YNJ and Boon, GJAM and Barco, S and Klok, FA and Siegerink, B}, title = {Eight lessons from 2 years of use of the Post-COVID-19 Functional Status scale.}, journal = {The European respiratory journal}, volume = {61}, number = {5}, pages = {}, pmid = {37080570}, issn = {1399-3003}, mesh = {Humans ; *COVID-19 ; Functional Status ; }, abstract = {Based on the literature and users’ experiences, lessons could be learned after 2 years’ use of the Post-COVID-19 Functional Status (PCFS) scale, that could contribute to its optimal use. All in all, the PCFS scale provided added value during the pandemic. https://bit.ly/3KkI5Ak}, } @article {pmid37078648, year = {2023}, author = {Tana, C and Giamberardino, MA and Martelletti, P}, title = {Long COVID and especially headache syndromes.}, journal = {Current opinion in neurology}, volume = {36}, number = {3}, pages = {168-174}, doi = {10.1097/WCO.0000000000001153}, pmid = {37078648}, issn = {1473-6551}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Headache/diagnosis/epidemiology/therapy ; *Migraine Disorders/complications ; }, abstract = {PURPOSE OF REVIEW: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache.

RECENT FINDINGS: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine. Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms.

SUMMARY: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.}, } @article {pmid37078006, year = {2023}, author = {Maffei, M and Mazzatenta, A and Origlia, N}, title = {Editorial: Loss of taste and smell in COVID-19 patients: A prognostic tool and a starting point to investigate the action of SARS-CoV-2 in the central nervous system.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1191227}, pmid = {37078006}, issn = {1662-5102}, } @article {pmid37077911, year = {2023}, author = {Park, J and Dean, LS and Jiyarom, B and Gangcuangco, LM and Shah, P and Awamura, T and Ching, LL and Nerurkar, VR and Chow, DC and Igno, F and Shikuma, CM and Devendra, G}, title = {Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1151780}, pmid = {37077911}, issn = {1664-3224}, support = {K12 HL143960/HL/NHLBI NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; T37 MD008636/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Monocytes/metabolism ; Leukocytes, Mononuclear ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19/pathology ; SARS-CoV-2 ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Monocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae of SARS-CoV-2 infection (PASC) are not fully elucidated.

METHODS: A cross-sectional study was conducted comparing plasma cytokine and monocyte levels among three groups: participants with pulmonary PASC (PPASC) with a reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; fully recovered from SARS-CoV-2 with no residual symptoms (recovered group, RG); and negative for SARS-CoV-2 (negative group, NG). The expressions of cytokines were measured in plasma of study cohort by Luminex assay. The percentages and numbers of monocyte subsets (classical, intermediate, and non-classical monocytes) and monocyte activation (defined by CD169 expression) were analyzed using flow cytometry analysis of peripheral blood mononuclear cells.

RESULTS: Plasma IL-1Ra levels were elevated but FGF levels were reduced in PG compared to NG. Circulating monocytes and three subsets were significantly higher in PG and RG compared to NG. PG and RG exhibited higher levels of CD169[+] monocyte counts and higher CD169 expression was detected in intermediate and non-classical monocytes from RG and PG than that found in NG. Further correlation analysis with CD169[+] monocyte subsets revealed that CD169[+] intermediate monocytes negatively correlated with DLCOc%, and CD169[+] non-classical monocytes positively correlated with IL-1α, IL-1β, MIP-1α, Eotaxin, and IFN-γ.

CONCLUSION: This study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Further, the results suggest that monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents. This observation will aid in understanding the immunopathologic feature of pulmonary PASC development, resolution, and subsequent therapeutic interventions.}, } @article {pmid37077670, year = {2023}, author = {Garrett, RE and Palacio, CH and Bar-Or, D}, title = {Long COVID: Is there a kidney link?.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1138644}, pmid = {37077670}, issn = {2296-858X}, abstract = {Metabolic causes such as altered bioenergetics and amino acid metabolism may play a major role in Long COVID. Renal-metabolic regulation is an integral part of these pathways but has not been systematically or routinely investigated in Long COVID. Here we discuss the biochemistry of renal tubular injury as it may contribute to Long COVID symptoms. We propose three potential mechanisms that could be involved in Long COVID namely creatine phosphate metabolism, un-reclaimed glomerular filtrate and COVID specific proximal tubule cells (PTC) injury-a tryptophan paradigm. This approach is intended to allow for improved diagnostics and therapy for the long-haul sufferers.}, } @article {pmid37077615, year = {2023}, author = {Mudgal, SK and Gaur, R and Rulaniya, S and T, L and Agarwal, R and Kumar, S and Varshney, S and Sharma, S and Bhattacharya, S and Kalyani, V}, title = {Pooled Prevalence of Long COVID-19 Symptoms at 12 Months and Above Follow-Up Period: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36325}, pmid = {37077615}, issn = {2168-8184}, abstract = {Current data suggests that coronavirus disease 2019 (COVID-19) survivors experience long-lasting problems. It is not yet understood how long these symptoms last. The goal of this study was to compile all the data that was currently available to evaluate COVID-19's long-term effects at 12 months and above. We looked for studies published by December 15, 2022, in PubMed and Embase that discussed follow-up findings for COVID-19 survivors who had been alive for at least a year. A random-effect model was carried out to determine the combined prevalence of different long-COVID symptoms. The Joanna Briggs Institute tool was used to assess the risk of bias for the included studies, and the I2 statistics were used to evaluate the heterogeneity. After reviewing 3,209 studies, 46 were deemed admissible, with an aggregate COVID-19 population of 17976. At 12 months and above, 57% of patients reported a minimum of one symptom, and the five most prevalent symptoms were: dyspnea on exertion (34%, 95% CI 0.2; 0.94); difficulty in concentration (32%, 95% CI 0.16; 0.52); fatigue (31%, 95% CI 0.22; 0.40); frailty (31%, 95% CI 0.06; 0.78); and arthromyalgia (28%, 95% CI 0.09; 0.6). The findings of the present study showed that at 12 months and beyond, a sizable fraction of COVID-19 survivors still have lasting symptoms that impair several body systems. Long-COVID patients require an urgent understanding of pathophysiological processes and the development of tailored treatments.}, } @article {pmid37077548, year = {2023}, author = {Radovanovic, D and D'Angelo, E}, title = {Lung pathophysiology in patients with long COVID-19: one size definitely does not fit all.}, journal = {ERJ open research}, volume = {9}, number = {2}, pages = {}, pmid = {37077548}, issn = {2312-0541}, abstract = {Despite reduced resting lung volumes and D LCO, patients with long COVID and dyspnoea have similar physiological response to exercise to healthy subjects. D LCO impairment can marginally explain heterogeneity of complex syndromes such as long COVID. https://bit.ly/40j4aX6.}, } @article {pmid37076602, year = {2023}, author = {Li, G and Hilgenfeld, R and Whitley, R and De Clercq, E}, title = {Therapeutic strategies for COVID-19: progress and lessons learned.}, journal = {Nature reviews. Drug discovery}, volume = {22}, number = {6}, pages = {449-475}, pmid = {37076602}, issn = {1474-1784}, mesh = {Animals ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Antiviral Agents/therapeutic use/pharmacology ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic strategies that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and/or human proteins to control viral infection, encompassing hundreds of potential drugs and thousands of patients in clinical trials. So far, a few small-molecule antiviral drugs (nirmatrelvir-ritonavir, remdesivir and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset. In addition, hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as tocilizumab and Janus kinase inhibitors such as baricitinib. Here, we summarize progress with COVID-19 drug discovery, based on accumulated findings since the pandemic began and a comprehensive list of clinical and preclinical inhibitors with anti-coronavirus activities. We also discuss the lessons learned from COVID-19 and other infectious diseases with regard to drug repurposing strategies, pan-coronavirus drug targets, in vitro assays and animal models, and platform trial design for the development of therapeutics to tackle COVID-19, long COVID and pathogenic coronaviruses in future outbreaks.}, } @article {pmid37076024, year = {2023}, author = {Norweg, A and Yao, L and Barbuto, S and Nordvig, AS and Tarpey, T and Collins, E and Whiteson, J and Sweeney, G and Haas, F and Leddy, J}, title = {Exercise intolerance associated with impaired oxygen extraction in patients with long COVID.}, journal = {Respiratory physiology & neurobiology}, volume = {313}, number = {}, pages = {104062}, pmid = {37076024}, issn = {1878-1519}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Oxygen Consumption/physiology ; *COVID-19 ; Exercise Test ; Oxygen ; Exercise Tolerance/physiology ; }, abstract = {OBJECTIVE: Chronic mental and physical fatigue and post-exertional malaise are the more debilitating symptoms of long COVID-19. The study objective was to explore factors contributing to exercise intolerance in long COVID-19 to guide development of new therapies. Exercise capacity data of patients referred for a cardiopulmonary exercise test (CPET) and included in a COVID-19 Survivorship Registry at one urban health center were retrospectively analyzed.

RESULTS: Most subjects did not meet normative criteria for a maximal test, consistent with suboptimal effort and early exercise termination. Mean O2 pulse peak % predicted (of 79 ± 12.9) was reduced, supporting impaired energy metabolism as a mechanism of exercise intolerance in long COVID, n = 59. We further identified blunted rise in heart rate peak during maximal CPET. Our preliminary analyses support therapies that optimize bioenergetics and improve oxygen utilization for treating long COVID-19.}, } @article {pmid37074754, year = {2024}, author = {Lenz, C and Slack, MPE and Shea, KM and Reinert, RR and Taysi, BN and Swerdlow, DL}, title = {Long-Term effects of COVID-19: a review of current perspectives and mechanistic insights.}, journal = {Critical reviews in microbiology}, volume = {50}, number = {3}, pages = {315-328}, doi = {10.1080/1040841X.2023.2190405}, pmid = {37074754}, issn = {1549-7828}, mesh = {Humans ; *COVID-19/epidemiology/virology ; *SARS-CoV-2 ; Risk Factors ; Cardiovascular Diseases/virology/epidemiology/etiology ; Comorbidity ; }, abstract = {Although SARS-CoV-2, responsible for COVID-19, is primarily a respiratory infection, a broad spectrum of cardiac, pulmonary, neurologic, and metabolic complications can occur. More than 50 long-term symptoms of COVID-19 have been described, and as many as 80% of patients may develop ≥1 long-term symptom. To summarize current perspectives of long-term sequelae of COVID-19, we conducted a PubMed search describing the long-term cardiovascular, pulmonary, gastrointestinal, and neurologic effects post-SARS-CoV-2 infection and mechanistic insights and risk factors for the above-mentioned sequelae. Emerging risk factors of long-term sequelae include older age (≥65 years), female sex, Black or Asian race, Hispanic ethnicity, and presence of comorbidities. There is an urgent need to better understand ongoing effects of COVID-19. Prospective studies evaluating long-term effects of COVID-19 in all body systems and patient groups will facilitate appropriate management and assess burden of care. Clinicians should ensure patients are followed up and managed appropriately, especially those in at-risk groups. Healthcare systems worldwide need to develop approaches to follow-up and support patients recovering from COVID-19. Surveillance programs can enhance prevention and treatment efforts for those most vulnerable.}, } @article {pmid37073410, year = {2023}, author = {Sedgley, R and Winer-Jones, J and Bonafede, M}, title = {Long COVID Incidence in a Large US Ambulatory Electronic Health Record System.}, journal = {American journal of epidemiology}, volume = {192}, number = {8}, pages = {1350-1357}, doi = {10.1093/aje/kwad095}, pmid = {37073410}, issn = {1476-6256}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Electronic Health Records ; COVID-19 Testing ; Incidence ; }, abstract = {Estimates of the prevalence of long-term symptoms of coronavirus disease 2019 (COVID-19), referred to as long COVID, vary widely. This retrospective cohort study describes the incidence of long COVID symptoms 12-20 weeks postdiagnosis in a US ambulatory care setting and identifies potential risk factors. We identified patients with and without a diagnosis of or positive test for COVID-19 between January 1, 2020, and March 13, 2022, in the Veradigm (Veradigm LLC, Chicago, Illinois) electronic health record database. We captured data on patient demographic characteristics, clinical characteristics, and COVID-19 comorbidity in the 12-month baseline period. We compared long COVID symptoms between matched cases and controls 12-20 weeks after the index date (COVID-19 diagnosis date (cases) or median visit date (controls)). Multivariable logistic regression was used to examine associations between baseline COVID-19 comorbid conditions and long COVID symptoms. Among 916,894 patients with COVID-19, 14.8% had at least 1 long COVID symptom in the 12-20 weeks postindex as compared with 2.9% of patients without documented COVID-19. Commonly reported symptoms were joint stiffness (4.5%), cough (3.0%), and fatigue (2.7%). Among patients with COVID-19, the adjusted odds of long COVID symptoms were significantly higher among patients with a baseline COVID-19 comorbid condition (odds ratio = 1.91, 95% confidence interval: 1.88, 1.95). In particular, prior diagnosis of cognitive disorder, transient ischemic attack, hypertension, or obesity was associated with higher odds of long COVID symptoms.}, } @article {pmid37073325, year = {2023}, author = {Morello, R and Mariani, F and Mastrantoni, L and De Rose, C and Zampino, G and Munblit, D and Sigfrid, L and Valentini, P and Buonsenso, D}, title = {Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study.}, journal = {EClinicalMedicine}, volume = {59}, number = {}, pages = {101961}, pmid = {37073325}, issn = {2589-5370}, abstract = {BACKGROUND: Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol.

METHODS: We performed a prospective "disease-based" cohort study between 01/02/2020 to 31/10/2022 including children aged 0-18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher's exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan-Meier method.

FINDINGS: 1243 children were included, median age: 7.5 (4-10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18-1.28), comorbidities (OR 1.68; 95% CI 1.14-2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91-12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC.

INTERPRETATION: In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed.

FUNDING: This study has been funded by Pfizer non-competitive grant, granted to DB (# 65925795).}, } @article {pmid37073192, year = {2023}, author = {Hassan, L and Ahsan, Z and Bint E Riaz, H}, title = {An Unusual Case of Blackout in a COVID-19 Patient: COVID-19 Brain Fog.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e36273}, pmid = {37073192}, issn = {2168-8184}, abstract = {This case report highlights a unique case of brain fog in a COVID-19 patient suggesting COVID-19's neurotropic nature. COVID-19 is associated with a long-COVID syndrome that presents with cognitive decline and fatigue. Recent studies show the emergence of a novel syndrome known as post-acute COVID syndrome or long COVID, which constitutes a variety of symptoms that continue for four weeks following the onset of a COVID-19 diagnosis. Numerous post-COVID patients experience both short and long-lasting symptoms affecting several organs, including the brain, which includes being unconscious, bradyphrenia, or amnesia. This long COVID status comprises of "brain fog", which, coupled with neuro-cognitive effects, has a significant role in prolonging the recovery phase. The pathogenesis of brain fog is currently unknown. One of the leading causes might be the involvement of neuroinflammation due to mast cells stimulated by pathogenic and stress stimuli. This in turn, triggers the release of mediators that activate microglia, causing inflammation in the hypothalamus. Its ability to invade the nervous system through trans-neural or hematogenous mechanisms is possibly the chief cause behind the presenting symptoms. This case report highlights a unique case of brain fog in a COVID-19 patient suggesting COVID-19's neurotropic nature and how it may lead to neurologic complications such as meningitis, encephalitis, and Guillain-Barré syndrome.}, } @article {pmid37072891, year = {2023}, author = {Fankuchen, O and Lau, J and Rajan, M and Swed, B and Martin, P and Hidalgo, M and Yamshon, S and Pinheiro, L and Shah, MA}, title = {Long COVID in Cancer: A Matched Cohort Study of 1-year Mortality and Long COVID Prevalence Among Patients With Cancer Who Survived an Initial Severe SARS-CoV-2 Infection.}, journal = {American journal of clinical oncology}, volume = {46}, number = {7}, pages = {300-305}, pmid = {37072891}, issn = {1537-453X}, support = {UL1 TR000457/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; Prevalence ; Aftercare ; Patient Discharge ; *Neoplasms/complications ; }, abstract = {OBJECTIVES: The long-term effects of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection in patients with cancer are unknown. We examined 1-year mortality and prevalence of long COVID in patients with and without cancer after initial hospitalization for acute COVID-19 infection.

METHODS: We previously studied 585 patients hospitalized from March to May 2020 with acute COVID-19 infection at Weill Cornell Medicine (117 patients with cancer and 468 age, sex, and comorbidity-matched non-cancer controls). Of the 456 patients who were discharged, we followed 359 patients (75 cancer and 284 non-cancer controls) for COVID-related symptoms and death, at 3, 6, and 12 months after initial symptom onset. Pearson χ 2 and Fisher exact tests were used to determine associations between cancer, postdischarge mortality, and long COVID symptoms. Multivariable Cox proportional hazards models adjusting for potential confounders were used to quantify the risk of death between patients with and without cancer.

RESULTS: The cancer cohort had higher mortality after hospitalization (23% vs 5%, P < 0.001), a hazard ratio of 4.7 (95% CI: 2.34-9.46) for all-cause mortality, after adjusting for smoking and oxygen requirement. Long COVID symptoms were observed in 33% of patients regardless of cancer status. Constitutional, respiratory, and cardiac complaints were the most prevalent symptoms in the first 6 months, whereas respiratory and neurological complaints (eg, "brain fog" and memory deficits) were most prevalent at 12 months.

CONCLUSIONS: Patients with cancer have higher mortality after hospitalization for acute severe acute respiratory syndrome coronavirus 2 infections. The risk of death was highest in the first 3 months after discharge. About one-third of all patients experienced long COVID.}, } @article {pmid37072092, year = {2023}, author = {Goetzl, EJ and Yao, PJ and Kapogiannis, D}, title = {Prediction of Post-Acute-Sequelae of COVID-19 by Cargo Protein Biomarkers of Blood Total Extracellular Vesicles in Acute COVID-19.}, journal = {The American journal of medicine}, volume = {136}, number = {8}, pages = {824-829}, pmid = {37072092}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Mitochondrial Proteins ; *Extracellular Vesicles ; Biomarkers ; Disease Progression ; }, abstract = {BACKGROUND: SARS-CoV-2 invades mitochondria of infected cells resulting in disordered metabolism, mitophagy, and abnormal levels of mitochondrial proteins in extracellular vesicles. Blood extracellular vesicle SARS-CoV-2 proteins and mitochondrial proteins were quantified in COVID-19 to assess possible roles as biomarkers.

METHODS: Total extracellular vesicles were precipitated from blood of age- and gender-matched participants with no infection (n=10), acute COVID-19 (n=16), post-acute sequelae of COVID-19 (PASC or long COVID) (n=30), or post-acute COVID without PASC (n=8) and their extracted proteins quantified by enzyme-linked immunosorbent assays (ELISAs).

RESULTS: Total extracellular vesicle levels of S1 (receptor-binding domain [RBD]) protein were significantly higher in acute infections than in uninfected controls, post-acute infection without PASC, and PASC. Total extracellular vesicle levels of nucleocapsid (N) protein were significantly higher in PASC than in uninfected controls, acute infections, and post-acute infection without PASC. Neither acute levels of S1(RBD) or N proteins predicted progression to PASC. Levels of neither SARS-CoV-2 protein in established PASC correlated with neuropsychiatric manifestations. Significant decreases in total extracellular vesicle levels of the mitochondrial proteins MOTS-c, VDAC-1, and humanin, and elevations of levels of SARM-1 were observed in acutely infected patients who would develop PASC. Significant decreases in total extracellular vesicle levels of MOTS-c and humanin, but not VDAC-1, and elevations of total extracellular vesicle levels of SARM-1 were characteristic of PASC patients with neuropsychiatric manifestations.

CONCLUSIONS: Total extracellular vesicle levels of SARS-CoV-2 proteins in COVID-19 indicate intracellular presence of SARS-CoV-2. Abnormal total extracellular vesicles levels of mitochondrial proteins in acute infections predict a high risk of PASC and later in established PASC are indicative of neuropsychiatric manifestations.}, } @article {pmid37072019, year = {2023}, author = {McGuire, WC and Pearce, AK and Malhotra, A}, title = {Sleep disturbances, dyspnoea, and anxiety in long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {664-665}, pmid = {37072019}, issn = {2213-2619}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Anxiety/etiology ; Sleep ; Dyspnea/etiology ; *Sleep Wake Disorders/etiology ; Depression ; }, } @article {pmid37072018, year = {2023}, author = {Jackson, C and Stewart, ID and Plekhanova, T and Cunningham, PS and Hazel, AL and Al-Sheklly, B and Aul, R and Bolton, CE and Chalder, T and Chalmers, JD and Chaudhuri, N and Docherty, AB and Donaldson, G and Edwardson, CL and Elneima, O and Greening, NJ and Hanley, NA and Harris, VC and Harrison, EM and Ho, LP and Houchen-Wolloff, L and Howard, LS and Jolley, CJ and Jones, MG and Leavy, OC and Lewis, KE and Lone, NI and Marks, M and McAuley, HJC and McNarry, MA and Patel, BV and Piper-Hanley, K and Poinasamy, K and Raman, B and Richardson, M and Rivera-Ortega, P and Rowland-Jones, SL and Rowlands, AV and Saunders, RM and Scott, JT and Sereno, M and Shah, AM and Shikotra, A and Singapuri, A and Stanel, SC and Thorpe, M and Wootton, DG and Yates, T and Gisli Jenkins, R and Singh, SJ and Man, WD and Brightling, CE and Wain, LV and Porter, JC and Thompson, AAR and Horsley, A and Molyneaux, PL and Evans, RA and Jones, SE and Rutter, MK and Blaikley, JF and , }, title = {Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {8}, pages = {673-684}, pmid = {37072018}, issn = {2213-2619}, support = {209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MR/T032529/1/MRC_/Medical Research Council/United Kingdom ; SP/17/16/33519/BHF_/British Heart Foundation/United Kingdom ; RE/18/3/34214/BHF_/British Heart Foundation/United Kingdom ; FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; MC_UU_00034/6/MRC_/Medical Research Council/United Kingdom ; COV0319/DH_/Department of Health/United Kingdom ; NIHR300669/DH_/Department of Health/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; RP-2017-08-ST2-014/DH_/Department of Health/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; 216606/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; NIHR203308/DH_/Department of Health/United Kingdom ; MR/V040162/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/complications/epidemiology ; Prospective Studies ; Hospitalization ; *Sleep Wake Disorders/epidemiology/etiology ; Sleep/physiology ; Hospitals ; United Kingdom/epidemiology ; Lung ; }, abstract = {BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea.

METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107).

FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect.

INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition.

FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.}, } @article {pmid37071159, year = {2023}, author = {Nouraeinejad, A}, title = {Memory loss in patients with long COVID can be due to reduced hippocampal neurogenesis.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {}, number = {}, pages = {1-2}, pmid = {37071159}, issn = {1433-8491}, } @article {pmid37071080, year = {2023}, author = {Lorente-Ros, M and Das, S and Elias, J and Frishman, WH and Aronow, WS}, title = {Cardiovascular Manifestations of the Long COVID Syndrome.}, journal = {Cardiology in review}, volume = {}, number = {}, pages = {}, doi = {10.1097/CRD.0000000000000552}, pmid = {37071080}, issn = {1538-4683}, abstract = {While most coronavirus 2019 (COVID-19) survivors have had complete resolution of symptoms, a significant proportion have suffered from incomplete recovery. Cardiopulmonary symptoms, such as dyspnea, chest pain, and palpitations are responsible for a substantial symptom burden in COVID-19 survivors. Studies have revealed persistent myocardial injury with late gadolinium enhancement and myocardial scar on cardiac magnetic resonance in a significant proportion of patients. Evidence of myocardial edema, active inflammation, left ventricular dysfunction, and right ventricular dysfunction, is limited to a minority of patients. Large observational studies of COVID-19 survivors have indicated an increased risk of cardiovascular disease compared to the general population, including the risk of coronary artery disease, cardiomyopathy, and arrhythmias. Management of long COVID is focused on supportive therapy to reduce systemic inflammation. Patients with high cardiovascular risk, namely, those who had cardiovascular complications during acute illness, patients who have new onset cardiopulmonary symptoms in the postinfectious period, and competitive athletes, should be evaluated by a cardiovascular specialist. Management of cardiovascular sequelae is currently based on general expert guideline recommendations given the lack of evidence specific to long COVID syndrome. In this review, we outline the cardiovascular manifestations of long COVID, the current evidence supporting cardiac abnormalities in the postinfectious period, and the recommended management of these patients.}, } @article {pmid37070997, year = {2023}, author = {Kooner, HK and McIntosh, MJ and Matheson, AM and Svenningsen, S and Parraga, G}, title = {More Data about [129]Xe MRI Ventilation Defects in Long COVID-19.}, journal = {Radiology}, volume = {307}, number = {4}, pages = {e230479}, pmid = {37070997}, issn = {1527-1315}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Magnetic Resonance Imaging ; Lung ; Xenon Isotopes ; }, } @article {pmid37070922, year = {2023}, author = {Hu, CL and Zheng, MJ and He, XX and Liu, DC and Jin, ZQ and Xu, WH and Lin, PY and Cheng, JW and Wei, QG}, title = {COVID-19 and bone health.}, journal = {European review for medical and pharmacological sciences}, volume = {27}, number = {7}, pages = {3191-3200}, doi = {10.26355/eurrev_202304_31953}, pmid = {37070922}, issn = {2284-0729}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Bone Density ; *Osteoporosis ; }, abstract = {A few patients who have recovered from COVID-19 develop persistent or new symptoms that last for weeks or months; this is called "long COVID" or "post-COVID-19 syndrome." Over time, awareness of the short- and long-term consequences of COVID-19 has increased. The pulmonary consequences are now fairly well established, but little is known about the extrapulmonary system of COVID-19, particularly its effects on bones. Current evidence and reports indicate a direct relationship between SARS-CoV-2 infection and bone health, with SARS-CoV-2 having a significant negative effect on bone health. In this review, we analyzed the impact of SARS-CoV-2 infection on bone health and assessed the impact of COVID-19 on the diagnosis and treatment of osteoporosis.}, } @article {pmid37070369, year = {2023}, author = {Keenan, PM and Doody, O}, title = {An update of the reported effects of the COVID-19 pandemic on person with intellectual disability and their carers: a scoping review.}, journal = {Annals of medicine}, volume = {55}, number = {1}, pages = {2196437}, pmid = {37070369}, issn = {1365-2060}, mesh = {Humans ; *COVID-19/epidemiology ; *Intellectual Disability/epidemiology ; Caregivers ; Pandemics ; Health Promotion ; }, abstract = {BACKGROUND: The effects of the COVID-19 pandemic has been felt by all groups in society and people with intellectual disability are especially vulnerable due to underlying conditions/health problems, multi-morbidity, limitations in understanding, frailty and social circumstances. This places people with intellectual disability, their families and carers at increased risk of stress and in need of support.

OBJECTIVE: To update and chart the evidence of the effects of the COVID-19 pandemic on people with intellectual disability, their families and carers reported within the research in 2021.

METHODS: A scoping review of research published in 2021 across 7 databases.

RESULTS: 84 studies met the inclusion criteria, and the findings highlight people with intellectual disability are at a greater risk to COVID-19 health outcomes due to underlying health concerns and access issues. The effects of COVID-19 can be seen from a personal, social and health perspective for people with intellectual disability, their carers and families. However, COVID-19 did have some unanticipated benefits such as: less demand on time, greater opportunity to engage with people of value and building resilience.

CONCLUSIONS: COVID-19 presents many challenges but for people with intellectual disability compounding existing obstacles encountered in access issues, service provision and supports available. There is a need to identify and describe the experiences of people with intellectual disability, their families and carers in the medium-long term during COVID-19. Greater supports and evidence of effective interventions to promote health, deliver services and support individual with intellectual disability is needed as there is little evidence of clinical care for people with intellectual disability during COVID-19.}, } @article {pmid37070120, year = {2023}, author = {Barisione, G and Brusasco, V}, title = {Lung diffusing capacities for nitric oxide and carbon monoxide at rest and post-walking in long COVID.}, journal = {ERJ open research}, volume = {9}, number = {2}, pages = {}, pmid = {37070120}, issn = {2312-0541}, abstract = {BACKGROUND: Approximately one-third of long coronavirus disease 2019 (long COVID) patients report breathlessness and fatigue even during activities of daily living. We hypothesised that abnormalities of combined diffusing capacity of the lung for nitric oxide (D LNO) and carbon monoxide (D LCO) at rest or after mild exercise are associated with breathlessness in patients with long COVID.

METHODS: Single-breath combined D LNO and D LCO were measured at rest and immediately after a short bout of treadmill exercise simulating ordinary walking in 32 Caucasian patients with long COVID and dyspnoea at rest. 20 subjects served as a control group.

RESULTS: At rest, combined D LNO, D LCO and alveolar volume (V A) were significantly lower in long COVID than in controls, with D LNO and D LCO being below the limits of normal in 69% and 41% of cases, respectively. Mean values of D LNO/V A and D LCO/V A in long COVID patients were less than controls, yet, in only 22% and 12% of long COVID patients were the values of D LNO/V A and D LCO/V A below the limits of normal. After treadmill exercise, D LNO, D LNO/D LCO, V A and heart rate increased significantly without differences between groups. D LNO remained below the limit of normal in 47% of long COVID patients.

CONCLUSION: These data suggest localised discrete loss of lung units in approximately half of long COVID patients, not completely explained by loss of V A or of alveolar-capillary recruitment during exercise.}, } @article {pmid37069814, year = {2023}, author = {Zhang, D and Zhou, Y and Ma, Y and Chen, P and Tang, J and Yang, B and Li, H and Liang, M and Xue, Y and Liu, Y and Zhang, J and Wang, X}, title = {Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge.}, journal = {Journal of Korean medical science}, volume = {38}, number = {15}, pages = {e120}, pmid = {37069814}, issn = {1598-6357}, support = {2020kfyXGYJ009//Fundamental Research Funds for the Central Universities/China ; 2020kfyXGYJ034//Fundamental Research Funds for the Central Universities/China ; 2020CFB809//Natural Science Foundation of Hubei Province/China ; WJ2021M234//Scientific Research Fund of Health Commission of Hubei Province/China ; }, mesh = {Dysbiosis/microbiology ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Humans ; Follow-Up Studies ; *COVID-19 ; *Gastrointestinal Microbiome/genetics ; Patient Discharge ; Clostridiales ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear.

METHODS: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19.

RESULTS: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group.

CONCLUSION: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.}, } @article {pmid37069455, year = {2023}, author = {Davis, HE and McCorkell, L and Vogel, JM and Topol, EJ}, title = {Author Correction: Long COVID: major findings, mechanisms and recommendations.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {6}, pages = {408}, doi = {10.1038/s41579-023-00896-0}, pmid = {37069455}, issn = {1740-1534}, } @article {pmid37069391, year = {2023}, author = {Fudge, JB}, title = {Long COVID immune phenotypes identified for blockade.}, journal = {Nature biotechnology}, volume = {41}, number = {4}, pages = {470}, doi = {10.1038/s41587-023-01765-0}, pmid = {37069391}, issn = {1546-1696}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Phenotype ; }, } @article {pmid37068983, year = {2023}, author = {Bouldin, E and Sandeep, S and Gillespie, A and Tkaczuk, A}, title = {Otolaryngologic Symptom Severity Post SARS-CoV-2 Infection.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, pmid = {37068983}, issn = {1873-4588}, abstract = {OBJECTIVE(S): To assess laryngologic symptomatology following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and determine whether symptom severity correlates with disease severity.

METHODS: Single-institution survey study in participants with documented SARS-CoV-2 infection between March 2020 and February 2021. Data acquired included demographic, infection severity characteristics, comorbidities, and current upper aerodigestive symptoms via validated patient reported outcome measures. Primary outcomes of interest were scores of symptom severity questionnaires. Coronavirus disease of 2019 (COVID-19) severity was defined by hospitalization status. Descriptive subgroup analyses were performed to investigate differences in demographics, comorbidities, and symptom severity in hospitalized participants stratified by ICU status. Multivariate logistical regression was used to evaluate significant differences in symptom severity scores by hospitalization status.

RESULTS: Surveys were distributed to 5300 individuals with upper respiratory infections. Ultimately, 470 participants with COVID-19 were included where 352 were hospitalized and 118 were not hospitalized. Those not hospitalized were younger (45.87 vs. 56.28 years), more likely female (74.17 vs. 58.92%), and less likely white (44.17 vs. 52.41%). Severity of dysphonia, dyspnea, cough, and dysphagia was significantly worse in hospitalized patients overall and remained worse at all time points. Cough severity paradoxically worsened in hospitalized respondents over time. Dyspnea scores remained abnormally elevated in respondents even 12 months after resolution of infection.

CONCLUSIONS: Results indicate that laryngologic symptoms are expected to be worse in patients hospitalized with COVID-19. Dyspnea and cough symptoms can be expected to persist or even worsen by 1-year post infection in those who were hospitalized. Dysphagia and dysphonia symptoms were mild. Nonhospitalized participants tended to have minimal residual symptoms by 1 year after infection.}, } @article {pmid37068519, year = {2023}, author = {Navis, A}, title = {A Review of Neurological Symptoms in Long COVID and Clinical Management.}, journal = {Seminars in neurology}, volume = {43}, number = {2}, pages = {286-296}, doi = {10.1055/s-0043-1767781}, pmid = {37068519}, issn = {1098-9021}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications/therapy ; SARS-CoV-2 ; Autoimmunity ; Fatigue ; }, abstract = {Long COVID is a clinical diagnosis generally referring to the persistence or development of new symptoms, affecting multiple organ systems after SARS-CoV-2 COVID-19 infection. Long COVID is thought to affect ∼20% of people after infection, including all age ranges and severity of infection. Fatigue, postexertional malaise, and respiratory and cardiac symptoms are commonly described. Neurological symptoms such as cognitive changes, sensory disturbances, headaches, and dysautonomia are common as well. The underlying pathophysiology remains unclear but immune dysregulation, autoimmunity, persistent viral reservoirs, and microvascular dysfunction have been implicated. As there are no tests at this time to diagnose long COVID, work-up should be focused on assessing reversible or treatable causes of symptoms. Furthermore, no treatments for long COVID currently exist, and management remains focused on a multimodal approach and symptom management, with many people showing improvement in symptoms over time.}, } @article {pmid37068113, year = {2023}, author = {Fung, KW and Baye, F and Baik, SH and Zheng, Z and McDonald, CJ}, title = {Prevalence and characteristics of long COVID in elderly patients: An observational cohort study of over 2 million adults in the US.}, journal = {PLoS medicine}, volume = {20}, number = {4}, pages = {e1004194}, pmid = {37068113}, issn = {1549-1676}, mesh = {Humans ; Adult ; Aged ; United States ; Cohort Studies ; Medicare ; Post-Acute COVID-19 Syndrome ; *Influenza, Human/epidemiology ; Prevalence ; *COVID-19 ; }, abstract = {BACKGROUND: Incidence of long COVID in the elderly is difficult to estimate and can be underreported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call "long Flu." In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients.

METHODS AND FINDINGS: This is a cohort study of Medicare (the US federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza, and residual symptoms. Long COVID was identified by (a) the designated long COVID code B94.8 (code-based definition), or (b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from 1 to 3 months post-infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in 4 outcome measures: (a) hospitalization (any cause); (b) hospitalization (for long COVID symptom); (c) emergency department (ED) visit (for long COVID symptom); and (d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients, respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell, and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) versus 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05 to 1.08, p < 0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) versus 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08 to 1.10, p < 0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified.

CONCLUSIONS: Relying on specific long COVID diagnostic codes results in significant underreporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.}, } @article {pmid37064788, year = {2023}, author = {Martins-Gonçalves, R and Hottz, ED and Bozza, PT}, title = {Acute to post-acute COVID-19 thromboinflammation persistence: Mechanisms and potential consequences.}, journal = {Current research in immunology}, volume = {4}, number = {}, pages = {100058}, pmid = {37064788}, issn = {2590-2555}, abstract = {Concerns for the long-term effects of COVID-19 infection have grown due to frequently reported persisting symptoms that can affect multiple systems for longer than 4 weeks after initial infection, a condition known as long-COVID-19 or post-acute COVID-19 syndrome (PACS). Even nonhospitalized survivors have an elevated risk for the development of thromboinflammatory-associated events, such as ischemic stroke and heart failure, pulmonary embolism and deep vein thrombosis. Recent findings point to the persistence of many mechanisms of hypercoagulability identified to be associated with disease severity and mortality in the acute phase of the disease, such as sustained inflammation and endotheliopathy, accompanied by abnormal fibrin generation and impaired fibrinolysis. Platelets seem to be central to the sustained hypercoagulable state, displaying hyperreactivity to stimuli and increased adhesive capacity. Platelets also contribute to elevated levels of thromboinflammatory mediators and pro-coagulant extracellular vesicles in individuals with ongoing PACS. Despite new advances in the understanding of mechanisms sustaining thromboinflammation in PACS, little is known about what triggers this persistence. In this graphical review, we provide a schematic representation of the known mechanisms and consequences of persisting thromboinflammation in COVID-19 survivors and summarize the hypothesized triggers maintaining this prothrombotic state.}, } @article {pmid37064319, year = {2023}, author = {Iqbal, P and Ata, F and Chaudhry, H and Muthanna, B and Waqas Younas, H and Munamm, SAU and Sharma, R and Fadah, K and Elazzazy, S and Hamad, A and Said Abu Tabar, O and Omar, NE}, title = {Post-COVID-19-associated multiorgan complications or "long COVID" with literature review and management strategy discussion: A meta-analysis.}, journal = {Health science reports}, volume = {6}, number = {4}, pages = {e1211}, pmid = {37064319}, issn = {2398-8835}, abstract = {OBJECTIVE: To investigate the post-COVID-19 long-term complications or long COVID of various organ systems in patients after 3 months of the infection, specifically before the Omicron variant, with comparative literature analysis.

METHODS: A systemic literature search and meta-analysis were conducted using multiple electronic databases (PubMed, Scopus, Cochrane library) with predefined search terms to identify eligible articles. Eligible studies reported long-term complications of COVID-19 infection before the Omicron variant infection. Case reports, case series, observational studies with cross-sectional or prospective research design, case-control studies, and experimental studies that reported post-COVID-19 complications were included. The complications reported after 3 months after the recovery from COVID-19 infection were included in the study.

RESULTS: The total number of studies available for analysis was 34. The effect size (ES) for neurological complications was 29% with 95% confidence interval (CI): 19%-39%. ES for psychiatric complications was 24% with 95% CI: 7%-41%. ES was 9% for cardiac outcomes, with a 95% CI of 1%-18%. ES was 22%, 95% CI: 5%-39% for the gastrointestinal outcome. ES for musculoskeletal symptoms was 18% with 95% CI: 9%-28%. ES for pulmonary complications was 28% with 95% CI: 18%-37%. ES for dermatological complications was 25%, with a 95% CI of 23%-26%. ES for endocrine outcomes was 8%, with a 95% CI of 8%-9%. ES size for renal outcomes was 3% with a 95% CI of 1%-7%. At the same time, other miscellaneous uncategorized outcomes had ES of 39% with 95% CI of 21%-57%. Apart from analyzing COVID-19 systemic complications outcomes, the ES for hospitalization and intensive care unit admissions were found to be 4%, 95% CI: 0%-7%, and 11% with 95% CI: 8%-14%.

CONCLUSION: By acquiring the data and statistically analyzing the post-COVID-19 complications during the prevalence of most virulent strains, this study has generated a different way of understanding COVID-19 and its complications for better community health.}, } @article {pmid37064315, year = {2023}, author = {Kim, J and Kwon, KH}, title = {Trends in eyebrow makeup after COVID-19 and long-COVID era.}, journal = {Health science reports}, volume = {6}, number = {4}, pages = {e1181}, pmid = {37064315}, issn = {2398-8835}, abstract = {BACKGROUND AND OBJECTIVES: The coronavirus disease-19 (COVID-19) pandemic, which began in 2019, is threatening millions of people around the world. Coronavirus, a severe acute respiratory syndrome, made it mandatory to wear masks, it was carried out through public awareness and review of changes in cosmetics.

METHODS: This literature review paper was written by referring to keywords such as "Eyebrow," "Permanent Make-up," "Microblading," "Make-up," and "COVID-19." The study selected a total of 485 references using representative journal search sites such as PubMed, Google Scholar, ResearchGate, RISS, DBPia, and CrossRef, of which a total of 43 papers were selected at the final stage from 2000 to 2022 using PRISMA flow diagram.

RESULTS: With the wearing of a mask due to COVID-19, we are paying attention to the change in the makeup trend caused by the preference for easy eye makeup.

CONCLUSIONS: This narrative review understands that eyebrow makeup has a significant impact on human images due to changes in makeup methods after the COVID-19 pandemic. It is expected to be used as important data for the rapidly growing semi-permanent makeup market.}, } @article {pmid37064029, year = {2023}, author = {Low, RN and Low, RJ and Akrami, A}, title = {A review of cytokine-based pathophysiology of Long COVID symptoms.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1011936}, pmid = {37064029}, issn = {2296-858X}, abstract = {The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with "brain fog," arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.}, } @article {pmid37063869, year = {2023}, author = {Huang, L and Qin, W and Guo, Z and Li, X and Li, F and Wang, X}, title = {Application of weighted gene co-expression network and immune infiltration for explorations of key genes in the brain of elderly COVID-19 patients.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1157179}, pmid = {37063869}, issn = {1664-3224}, mesh = {Aged ; Humans ; *COVID-19/genetics ; Brain ; Genes, Regulator ; *Brain Injuries ; *Asthma ; }, abstract = {INTRODUCTION: Although many studies have demonstrated the existing neurological symptoms in COVID-19 patients, the mechanisms are not clear until now. This study aimed to figure out the critical molecular and immune infiltration situations in the brain of elderly COVID-19 patients.

METHODS: GSE188847 was used for the differential analysis, WGCNA, and immune infiltration analysis. We also performed GO, KEGG, GSEA, and GSVA for the enrich analysis.

RESULTS: 266 DEGs, obtained from the brain samples of COVID-19 and non-COVID-19 patients whose ages were over 70 years old, were identified. GO and KEGG analysis revealed the enrichment in synapse and neuroactive ligand-receptor interaction in COVID-19 patients. Further analysis found that asthma and immune system signal pathways were significant changes based on GSEA and GSVA. Immune infiltration analysis demonstrated the imbalance of CD8+ T cells, neutrophils, and HLA. The MEpurple module genes were the most significantly different relative to COVID-19. Finally, RPS29, S100A10, and TIMP1 were the critical genes attributed to the progress of brain damage.

CONCLUSION: RPS29, S100A10, and TIMP1 were the critical genes in the brain pathology of COVID-19 in elderly patients. Our research has revealed a new mechanism and a potential therapeutic target.}, } @article {pmid37061998, year = {2023}, author = {Allan-Blitz, LT and Akbari, O and Kojima, N and Saavedra, E and Chellamuthu, P and Denny, N and MacMullan, MA and Hess, V and Shacreaw, M and Brobeck, M and Turner, F and Slepnev, VI and Ibrayeva, A and Klausner, JD}, title = {Unique immune and inflammatory cytokine profiles may define long COVID syndrome.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {6}, pages = {2925-2930}, pmid = {37061998}, issn = {1591-9528}, support = {R01 AI169687/AI/NIAID NIH HHS/United States ; R01 HL151493/HL/NHLBI NIH HHS/United States ; R01 HL159804/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Leukotriene E4 ; TNF Receptor-Associated Factor 2 ; SARS-CoV-2 ; Ubiquitin-Protein Ligases ; Cytokines ; }, abstract = {PURPOSE: Long COVID is estimated to occur in 5-10% of individuals after acute SARS-CoV-2 infection. However, the pathophysiology driving the disease process is poorly understood.

METHODS: We evaluated urine and plasma inflammatory and immune cytokine profiles in 33 individuals with long COVID compared to 33 who were asymptomatic and recovered, and 34 without prior infection.

RESULTS: Mean urinary leukotriene E4 was significantly elevated among individuals with long COVID compared to asymptomatic and recovered individuals (mean difference 774.2 pg/mL; SD 335.7) and individuals without prior SARS-CoV-2 infection (mean difference 503.1 pg/ml; SD 467.7). Plasma chemokine ligand 6 levels were elevated among individuals with long COVID compared to individuals with no prior SARS-CoV-2 infection (mean difference 0.59 units; SD 0.42). We found no significant difference in angiotensin-converting enzyme 2 antibody levels. Plasma tumor necrosis factor receptor-associated factor 2 (TRAF2) levels were reduced among individuals with long COVID compared to individuals who were asymptomatic and recovered (mean difference = 0.6 units, SD 0.46). Similarly, the mean level of Sarcoma Homology 2-B adapter protein 3 was 3.3 units (SD 1.24) among individuals with long COVID, lower than 4.2 units (SD 1.1) among individuals with recovered, asymptomatic COVID.

CONCLUSION: Our findings suggest that further studies should be conducted to evaluate the role of leukotriene E4 as a potential biomarker for a diagnostic test. Furthermore, based on reductions in TRAF2, long COVID may be driven in part by impaired TRAF2-dependent immune-mediated inflammation and potentially immune exhaustion.}, } @article {pmid37061399, year = {2024}, author = {Chuang, HJ and Lin, CW and Hsiao, MY and Wang, TG and Liang, HW}, title = {Long COVID and rehabilitation.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {123 Suppl 1}, number = {}, pages = {S61-S69}, pmid = {37061399}, issn = {0929-6646}, mesh = {Adult ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; Exercise Therapy ; Dyspnea ; }, abstract = {Coronavirus disease 2019 (COVID-19) has caused tremendous morbidity and mortality worldwide. The large number of post-COVID survivors has drawn attention to the management of post-COVID condition, known as long COVID. This review examines current knowledge of long COVID, regarding its epidemiology, mechanism, and clinical presentations in both adults and children. We also review the rehabilitation principles, modules, and effects, and share Taiwan's efforts to provide a top-down, nationwide care framework for long COVID patients. Dyspnea, chronic cough, and fatigue are the most commonly reported symptoms in the first 6 months after infection, but cognitive impairment and psychological symptoms may persist beyond this time. Several possible mechanisms behind these symptoms were proposed, but remained unconfirmed. These symptoms negatively impact individuals' function, activities, participation and quality of life. Rehabilitation is a key element of management to achieve functional improvement. Early management should start with comprehensive evaluation and identification of red flags. Exercise-based therapy, an essential part of management of long COVID, can be conducted with different modules, including telerehabilitation. Post-exertional symptom exacerbation and orthostatic hypotension should be carefully monitored during exercise. Randomized control trials with a large sample size are needed to determine the optimal timing, dosage, and modules.}, } @article {pmid37060396, year = {2023}, author = {Zuin, M and Rigatelli, G and Bilato, C and Pasquetto, G and Mazza, A}, title = {Risk of Incident New-Onset Arterial Hypertension After COVID-19 Recovery: A Systematic Review and Meta-analysis.}, journal = {High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension}, volume = {30}, number = {3}, pages = {227-233}, pmid = {37060396}, issn = {1179-1985}, mesh = {Male ; Humans ; Female ; Middle Aged ; *COVID-19/diagnosis/epidemiology ; *Hypertension/diagnosis/epidemiology ; Comorbidity ; Risk Factors ; *Neoplasms ; }, abstract = {INTRODUCTION: Arterial Hypertension (HT) has been described as a common comorbidity and independent risk factor of short-term outcome in COVID-19 patients. However, data regarding the risk of new-onset HT during the post-acute phase of COVID-19 are scant.

AIM: We assess the risk of new-onset HT in COVID-19 survivors within one year from the index infection by a systematic review and meta-analysis of the available data.

METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to February 11, 2023, and reporting the long-term risk of new-onset HT in COVID-19 survivors. Risk data were pooled using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI). Heterogeneity among studies was assessed using I[2] statistic.

RESULTS: Overall, 19,293,346 patients (mean age 54.6 years, 54.6% males) were included in this analysis. Of them, 758,698 survived to COVID-19 infection. Over a mean follow-up of 6.8 months, new-onset HT occurred to 12.7 [95% CI 11.4-13.5] out of 1000 patients survived to COVID-19 infection compared to 8.17 [95% CI 7.34-8.53] out of 1000 control subjects. Pooled analysis revealed that recovered COVID-19 patients presented an increased risk of new-onset HT (HR 1.70, 95% CI 1.46-1.97, p < 0.0001, I[2] = 78.9%) within seven months. This risk was directly influenced by age (p = 0.001), female sex (p = 0.03) and cancer (p < 0.0001) while an indirect association was observed using the follow-up length as moderator (p < 0.0001).

CONCLUSIONS: Our findings suggest that new-onset HT represents an important post-acute COVID-19 sequelae.}, } @article {pmid37056914, year = {2023}, author = {Otani, K and Fukushima, H and Matsuishi, K}, title = {COVID-19 delirium and encephalopathy: Pathophysiology assumed in the first 3 years of the ongoing pandemic.}, journal = {Brain disorders (Amsterdam, Netherlands)}, volume = {10}, number = {}, pages = {100074}, pmid = {37056914}, issn = {2666-4593}, abstract = {BACKGROUND: The coronavirus disease (COVID-19) continues to spread worldwide. It has a high rate of delirium, even in young patients without comorbidities. Infected patients required isolation because of the high infectivity and virulence of COVID-19. The high prevalence of delirium in COVID-19 primarily results from encephalopathy and neuroinflammation caused by acute respiratory distress syndrome (ARDS)-associated cytokine storm. Acute respiratory distress syndrome has been linked to delirium and psychotic symptoms in the subacute phase (4 to 12 weeks), termed post-acute COVID-19 syndrome (PACS), and to brain fog, cognitive dysfunction, and fatigue, termed "long COVID," which persists beyond 12 weeks. However, no review article that mentions "COVID-19 delirium" have never been reported.

BASIC PROCEDURES: This narrative review summarizes data on delirium associated with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and related neurological symptoms of persistent post-infection illness (PACS or long COVID) after persistence of cognitive dysfunction. Thus, we describe the pathophysiological hypothesis of COVID-19 delirium and its continuation as long COVID. This review also describes the treatment of delirium complicated by COVID-19 pneumonia.

MAIN FINDINGS: SARS-CoV-2 infection is associated with encephalopathy and delirium. An association between COVID-19 infection and Alzheimer's disease has been suggested, and studies are being conducted from multiple facets including genetics, cytology, and postmortem study.

PRINCIPAL CONCLUSIONS: This review suggests that COVID-19 has important short and long-term neuropsychiatric effects. Several hypotheses have been proposed that highlight potential neurobiological mechanisms as causal factors, including neuronal-inflammatory pathways by cytokine storm and cellular senescence, and chronic inflammation.}, } @article {pmid37056777, year = {2023}, author = {Polyak, MJ and Abrahamyan, L and Bego, MG}, title = {Editorial: Immune determinants of COVID-19 protection and disease: A focus on asymptomatic COVID and long COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1185693}, pmid = {37056777}, issn = {1664-3224}, support = {10029030//CIHR/Canada ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; COVID-19 Testing ; }, } @article {pmid37056649, year = {2023}, author = {Lukkahatai, N and Rodney, T and Ling, C and Daniel, B and Han, HR}, title = {Long COVID in the context of social determinants of health.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1098443}, pmid = {37056649}, issn = {2296-2565}, mesh = {Humans ; COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines/administration & dosage ; Pandemics ; *Post-Acute COVID-19 Syndrome/epidemiology ; *Social Determinants of Health/statistics & numerical data ; World Health Organization ; Male ; Female ; Adult ; Middle Aged ; Aged ; }, abstract = {The COVID-19 pandemic has been a challenge for the public health system and has highlighted health disparities. COVID-19 vaccines have effectively protected against infection and severe disease, but some patients continue to suffer from symptoms after their condition is resolved. These post-acute sequelae, or long COVID, continues to disproportionately affect some patients based on their social determinants of health (SDOH). This paper uses the World Health Organization's (WHO) SDOH conceptual framework to explore how SDOH influences long COVID outcomes.}, } @article {pmid37055567, year = {2023}, author = {Zhang, HG and Honerlaw, JP and Maripuri, M and Samayamuthu, MJ and Beaulieu-Jones, BR and Baig, HS and L'Yi, S and Ho, YL and Morris, M and Panickan, VA and Wang, X and Weber, GM and Liao, KP and Visweswaran, S and Tan, BWQ and Yuan, W and Gehlenborg, N and Muralidhar, S and Ramoni, RB and , and Kohane, IS and Xia, Z and Cho, K and Cai, T and Brat, GA}, title = {Potential pitfalls in the use of real-world data for studying long COVID.}, journal = {Nature medicine}, volume = {29}, number = {5}, pages = {1040-1043}, pmid = {37055567}, issn = {1546-170X}, support = {T15 LM007092/LM/NLM NIH HHS/United States ; FS/19/52/34563/BHF_/British Heart Foundation/United Kingdom ; R01 LM013345/LM/NLM NIH HHS/United States ; R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Research ; }, } @article {pmid37055494, year = {2023}, author = {Magnusson, K and Turkiewicz, A and Flottorp, SA and Englund, M}, title = {Prevalence of long COVID complaints in persons with and without COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6074}, pmid = {37055494}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; Prospective Studies ; Fatigue/epidemiology ; }, abstract = {We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18-70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5-6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6-13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.}, } @article {pmid37055492, year = {2023}, author = {Vasilevskaya, A and Mushtaque, A and Tsang, MY and Alwazan, B and Herridge, M and Cheung, AM and Tartaglia, MC}, title = {Sex and age affect acute and persisting COVID-19 illness.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6029}, pmid = {37055492}, issn = {2045-2322}, mesh = {Humans ; Female ; Male ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; SARS-CoV-2 ; Ambulatory Care Facilities ; }, abstract = {Long COVID is associated with neurological and neuropsychiatric manifestations. We conducted an observational study on 97 patients with prior SARS-CoV-2 infection and persisting cognitive complaints that presented to the University Health Network Memory Clinic between October 2020 and December 2021. We assessed the main effects of sex, age, and their interaction on COVID-19 symptoms and outcomes. We also examined the relative contribution of demographics and acute COVID-19 presentation (assessed retrospectively) on persistent neurological symptoms and cognition. Among our cohort, males had higher hospitalization rates than females during the acute COVID-19 illness (18/35 (51%) vs. 15/62 (24%); P = .009). Abnormal scores on cognitive assessments post-COVID were associated with older age (AOR = 0.84; 95% CI 0.74-0.93) and brain fog during initial illness (AOR = 8.80; 95% CI 1.76-65.13). Female sex (ARR = 1.42; 95% CI 1.09-1.87) and acute shortness of breath (ARR = 1.41; 95% CI 1.09-1.84) were associated with a higher risk of experiencing more persistent short-term memory symptoms. Female sex was the only predictor associated with persistent executive dysfunction (ARR = 1.39; 95% CI 1.12-1.76) and neurological symptoms (ARR = 1.66; 95% CI 1.19-2.36). Sex differences were evident in presentations and cognitive outcomes in patients with long COVID.}, } @article {pmid37055095, year = {2023}, author = {Kewalramani, N and Heenan, KM and McKeegan, D and Chaudhuri, N}, title = {Post-COVID Interstitial Lung Disease-The Tip of the Iceberg.}, journal = {Immunology and allergy clinics of North America}, volume = {43}, number = {2}, pages = {389-410}, pmid = {37055095}, issn = {1557-8607}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Lung Diseases, Interstitial/diagnosis/epidemiology/etiology ; *Respiration Disorders ; }, abstract = {The proportion of symptomatic patients with post-coronavirus 2019 (COVID-19) condition (long COVID) represents a significant burden on the individual as well as on the health care systems. A greater understanding of the natural evolution of symptoms over a longer period and the impacts of interventions will improve our understanding of the long-term impacts of the COVID-19 disease. This review will discuss the emerging evidence for the development of post-COVID interstitial lung disease focusing on the pathophysiological mechanisms, incidence, diagnosis, and impact of this potentially new and emerging respiratory disease.}, } @article {pmid37054916, year = {2023}, author = {Krinsky, N and Sizikov, S and Nissim, S and Dror, A and Sas, A and Prinz, H and Pri-Or, E and Perek, S and Raz-Pasteur, A and Lejbkowicz, I and Cohen-Matsliah, SI and Almog, R and Chen, N and Kurd, R and Jarjou'i, A and Rokach, A and Ben-Chetrit, E and Schroeder, A and Caulin, AF and Yost, CC and Schiffman, JD and Goldfeder, M and Martinod, K}, title = {NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {9}, pages = {2569-2584}, pmid = {37054916}, issn = {1538-7836}, support = {R01 HD093826/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Israel ; *COVID-19 ; *Extracellular Traps ; Neutrophils ; Cohort Studies ; DNA ; }, abstract = {BACKGROUND: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality.

OBJECTIVES: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID.

METHODS: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma.

RESULTS: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients.

CONCLUSIONS: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.}, } @article {pmid37054413, year = {2023}, author = {Cheng, AM and Dollar, E and Angier, H}, title = {Outpatient Management of COVID-19: Rapid Evidence Review.}, journal = {American family physician}, volume = {107}, number = {4}, pages = {370-381}, pmid = {37054413}, issn = {1532-0650}, mesh = {Humans ; *COVID-19 ; *Outpatients ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {New COVID-19 variants of concern continue to develop. Incubation period, transmissibility, immune escape, and treatment effectiveness differ by variants of concern. Physicians should be aware that the characteristics of the predominant variants of concern determine aspects of diagnosis and treatment. Multiple testing modalities exist; the most appropriate testing strategy varies depending on the clinical scenario, with factors of test sensitivity, turnaround time, and the expertise required for specimen collection. Three types of vaccines are available in the United States, and all people six months and older should be encouraged to receive one because vaccination is effective in reducing the incidence of and hospitalizations and deaths associated with COVID-19. Vaccination may also reduce the incidence of post-acute sequelae of SARS-CoV-2 infection (i.e., long COVID). Consider medications, such as nirmatrelvir/ritonavir, as first-line treatment for eligible patients diagnosed with COVID-19 unless logistical or supply constraints occur. National Institutes of Health guidelines and local health care partner resources can be used to determine eligibility. Long-term health effects of having COVID-19 are under investigation.}, } @article {pmid37052263, year = {2023}, author = {Victor, MM and Müller Haas, L and Grevet, EH and Rohde, LA}, title = {Successful Treatment of Post-COVID-19 ADHD-like Syndrome: A Case Report.}, journal = {Journal of attention disorders}, volume = {27}, number = {10}, pages = {1092-1098}, pmid = {37052263}, issn = {1557-1246}, mesh = {Adult ; Humans ; Middle Aged ; *Attention Deficit Disorder with Hyperactivity/complications/drug therapy ; *Central Nervous System Stimulants/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {Despite inattention being one of the most common symptoms of Post-COVID-19 Syndrome (PCS), there is a gap in the literature regarding its treatment. This report presents a case of attentional symptoms and fatigue that emerged after the SARS-CoV-2 infection. The symptoms were similar to ADHD in adults, although the 61-year-old patient had never experienced inattention symptoms before. The patient was initially treated with Methylphenidate and then Lisdexamfetamine. Both were adapted to the needs and treatment response presented by the patient. After several changes in the therapeutic regimen, including the addition of Bupropion, the patient achieved remission of his symptoms. This case highlights the importance of treating PCS inattention and fatigue as an ADHD-like syndrome, despite the evident different etiology of symptoms. It would be necessary to replicate these findings to confirm our results, thus benefiting other patients currently affected by this syndrome.}, } @article {pmid37052043, year = {2023}, author = {Grishechkina, IA and Lobanov, AA and Andronov, SV and Rachin, AP and Fesyun, AD and Ivanova, EP and Masiero, S and Maccarone, MC}, title = {Long-term outcomes of different rehabilitation programs in patients with long COVID syndrome: a cohort prospective study.}, journal = {European journal of translational myology}, volume = {33}, number = {2}, pages = {}, pmid = {37052043}, issn = {2037-7452}, abstract = {After the resolution of the acute SARS-COV-2 infection, an important percentage of patients do not fully recover and continue to present several symptoms. Nevertheless, there is a lack of data in the literature on the effects of rehabilitation programs on medium- and long-term long COVID symptoms. Therefore, the aim of this study was to evaluate the long-term outcomes after rehabilitation programs in long COVID syndrome patients. A prospective cohort study was conducted from August 2021 to March 2022, involving 113 patients with long COVID syndrome. The patients in the experimental group (EG, n=25) received a tailored and multidisciplinary rehabilitative program, involving aquatic exercises, respiratory and motor exercises, social integration training and neuropsychologic sessions, LASER therapy and magnetotherapy. Patients in the other three comparison groups received eastern medicine techniques (CG1), balneotherapy and physiotherapy (group CG2), self-training and home-based physical exercise (CG3). Once the several rehabilitation protocols had been performed, a structured telephone contact was made with the patients after 6 months ± 7 days from the end of the rehabilitation treatment, in order to record the frequency of hospital ad-missions due to exacerbation of post-exacerbation syndrome, death or disability, and the need for other types of care or drugs. The patients in the comparison groups were more likely to request therapeutic care for emerging long COVID symptoms (χ2=6.635, p=0.001; χ2=13.463, p=0.001; χ2=10.949, p=0.001, respectively), as well as more likely to be hospitalized (χ2=5.357, p=0.021; χ2=0.125, p=0.724; χ2=0.856, p=0.355, respectively) when compared to the patients of the EG. The relative risk (RR) of hospital admissions in the observed cohort was 0.143 ±1,031 (СI: 0.019; 1.078); 0.580±1,194 (CI: 0.056; 6.022); 0,340±1,087 (CI: 0.040; 2.860). The RR of hospital admissions for patients with long COVID syndrome was reduced by 85.7%; 42.0% and 66.0%, respectively, when the experimental rehabilitation technique was employed. In conclusion, a tailored and multidisciplinary rehabilitative program seems to have a better preventive effect not only in the short term, but also over the next 6 months, avoiding the new onset of disabilities and the use of medicines and specialist advice, than other rehabilitative programs. Future studies will need to further investigate these aspects to identify the best rehabilitation therapy, also in terms of cost-effectiveness, for these patients.}, } @article {pmid37051747, year = {2023}, author = {di Filippo, L and Frara, S and Nannipieri, F and Cotellessa, A and Locatelli, M and Rovere Querini, P and Giustina, A}, title = {Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {108}, number = {10}, pages = {e1106-e1116}, pmid = {37051747}, issn = {1945-7197}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Vitamin D ; *Vitamin D Deficiency/complications/epidemiology/diagnosis ; Vitamins ; Survivors ; }, abstract = {CONTEXT: Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors.

OBJECTIVE: Due to the extraskeletal effects of vitamin D, we retrospectively assessed the association between 25(OH) vitamin D levels and long COVID in COVID-19 survivors 6 months after hospitalization.

METHODS: Long COVID was defined according to NICE guidelines. Fifty long COVID and 50 non-long-COVID subjects matched on a 1:1 basis were enrolled from an outpatient clinic post-COVID cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin D/bone metabolism, and/or admission to the intensive care unit during hospitalization were exclusion criteria. 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge.

RESULTS: We observed lower 25(OH) vitamin D levels, evaluated at follow-up, in subjects with long COVID than those without (20.1 vs 23.2 ng/mL, P = .03). Regarding the affected health areas evaluated in the entire cohort, we observed lower 25(OH) vitamin D levels in those with neurocognitive symptoms at follow-up (n = 7) than those without (n = 93) (14.6 vs 20.6 ng/mL, P = .042). In patients presenting vitamin D deficiency (<20 ng/mL), both at admission and at follow-up (n = 42), those affected by long COVID (n = 22) presented lower 25(OH) vitamin D levels at follow-up than those not affected (n = 20) (12.7 vs 15.2 ng/mL, P = .041). In multiple regression analyses, lower 25(OH) vitamin D levels at follow-up were the only variable significantly associated with long COVID in our cohort (P = .008, OR 1.09, CI 1.01-1.16).

CONCLUSION: COVID-19 survivors with long COVID have lower 25(OH) vitamin D levels than matched patients without long COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge. The role of vitamin D supplementation as a preventive strategy of COVID-19 sequelae should be tested in randomized controlled trials.}, } @article {pmid37051252, year = {2023}, author = {Hurler, L and Szilágyi, Á and Mescia, F and Bergamaschi, L and Mező, B and Sinkovits, G and Réti, M and Müller, V and Iványi, Z and Gál, J and Gopcsa, L and Reményi, P and Szathmáry, B and Lakatos, B and Szlávik, J and Bobek, I and Prohászka, ZZ and Förhécz, Z and Csuka, D and Kajdácsi, E and Cervenak, L and Kiszel, P and Masszi, T and Vályi-Nagy, I and Würzner, R and , and Lyons, PA and Toonen, EJM and Prohászka, Z}, title = {Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1162171}, pmid = {37051252}, issn = {1664-3224}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/genetics ; SARS-CoV-2 ; Genotype ; Lectins ; Patient Acuity ; *Mannose-Binding Lectin/genetics ; }, abstract = {INTRODUCTION: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.

METHODS: We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.

RESULTS: We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.

CONCLUSION: In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.}, } @article {pmid37051070, year = {2023}, author = {Negi, K and Agarwal, M and Pahuja, I and Bhardwaj, B and Rawat, M and Bhaskar, A and Dwivedi, VP}, title = {Combating the challenges of COVID-19 pandemic: Insights into molecular mechanisms, immune responses and therapeutics against SARS-CoV-2.}, journal = {Oxford open immunology}, volume = {4}, number = {1}, pages = {iqad001}, pmid = {37051070}, issn = {2633-6960}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes lethal coronavirus disease (COVID-19). SARS-CoV-2 has been the chief source of threat to public health and safety from 2019 to the present. SARS-CoV-2 caused a sudden and significant rise in hospitalization due to respiratory issues and pneumonia. We are consistently uncovering new information about SARS-CoV-2, and yet so much is to explore to implement efficient interventions to combat the emergent variants and spread of the ongoing pandemic. Information regarding the existing COVID-19 pandemic is streamlining continuously. However, clinical symptoms of SARS-CoV-2 infections spanning from asymptomatic infection to severe death-instigating disease remain consistent with preliminary reports. In this review, we have briefly introduced highlights of the COVID-19 pandemic and features of SARS-CoV-2. We have focused on current knowledge of innate and adaptive immune responses during SARS-CoV-2 infections and persisting clinical features of recovered patients. Furthermore, we have discussed how these immune responses are not tightly regulated and imbalance can direct the latter phases of COVID-19, long-COVID symptoms, and cause detrimental immunopathogenesis. COVID-19 vaccines are also discussed in detail to describe the efforts going around the world to control and prevent the infection. Overall, we have summarized the current knowledge on the immunology of SARS-CoV-2 infection and the utilization of that knowledge in the development of a suitable COVID-19 therapeutics and vaccines.}, } @article {pmid37048757, year = {2023}, author = {Bamps, L and Armenti, JP and Bojan, M and Grandbastien, B and von Garnier, C and Du Pasquier, R and Desgranges, F and Papadimitriou-Olivgeris, M and Alberio, L and Preisig, M and Schwitter, J and Guery, B and The RegCOVID Study Group, }, title = {Long-Term Consequences of COVID-19: A 1-Year Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {7}, pages = {}, pmid = {37048757}, issn = {2077-0383}, abstract = {Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.}, } @article {pmid37048697, year = {2023}, author = {Bostanci, A and Gazi, U and Tosun, O and Suer, K and Unal Evren, E and Evren, H and Sanlidag, T}, title = {Long-COVID-19 in Asymptomatic, Non-Hospitalized, and Hospitalized Populations: A Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {7}, pages = {}, pmid = {37048697}, issn = {2077-0383}, abstract = {A substantial proportion of coronavirus disease 2019 (COVID-19) survivors continue to suffer from long-COVID-19 (LC) symptoms. Our study aimed to determine the risk factors for LC by using a patient population from Northern Cyprus. Subjects who were diagnosed with severe acute respiratory syndrome-2 (SARS-CoV-2) infection in our university hospital were invited and asked to fill in an online questionnaire. Data from 296 survivors who had recovered from COVID-19 infection at least 28 days prior the study was used in the statistical analysis. For determination of risk factors for "ongoing symptomatic COVID-19 (OSC)" and "Post-COVID-19 (PSC)" syndromes, the patient population was further divided into group 1 (Gr1) and group 2 (Gr2), that included survivors who were diagnosed with COVID-19 within 4-12 weeks and at least three months prior the study, respectively. The number of people with post-vaccination SARS-CoV-2 infection was 266 (89.9%). B.1.617.2 (Delta) (41.9%) was the most common SARS-CoV-2 variant responsible for the infections, followed by BA.1 (Omicron) (34.8%), B.1.1.7 (Alpha) (15.5%), and wild-type SARS-CoV-2 (7.8%). One-hundred-and-nineteen volunteers (40.2%) stated an increased frequency of COVID-19-related symptoms and experienced the symptoms in the week prior to the study. Of those, 81 (38.8%) and 38 (43.7%) were from Gr1 and Gr2 groups, respectively. Female gender, chronic illness, and symptomatic status at PCR testing were identified as risk factors for developing OSC syndrome, while only the latter showed a similar association with PSC symptoms. Our results also suggested that ongoing and persistent COVID-19-related symptoms are not influenced by the initial viral cycle threshold (Ct) values of the SARS-CoV-2, SARS-CoV-2 variant as well as vaccination status and type prior to COVID-19. Therefore, strategies other than vaccination are needed to combat the long-term effect of COVID-19, especially after symptomatic SARS-CoV-2 infection, and their possible economic burden on healthcare settings.}, } @article {pmid37048602, year = {2023}, author = {Galluzzo, V and Zazzara, MB and Ciciarello, F and Tosato, M and Martone, AM and Pais, C and Savera, G and Calvani, R and Picca, A and Marzetti, E and Landi, F and On Behalf Of Gemelli Against Covid-Post-Acute Care Team, }, title = {Inadequate Physical Activity Is Associated with Worse Physical Function in a Sample of COVID-19 Survivors with Post-Acute Symptoms.}, journal = {Journal of clinical medicine}, volume = {12}, number = {7}, pages = {}, pmid = {37048602}, issn = {2077-0383}, abstract = {Background-Patients affected by Long COVID often report shorter times spent doing physical activity (PA) after COVID-19. The aim of the present study was to evaluate potential associations between PA levels and parameters of physical function in a cohort of COVID-19 survivors with post-acute symptoms, with a particular focus on individuals aged 65 and older. Materials and methods-PA levels before and after COVID-19 were assessed in a sample of patients that had recovered from COVID-19 and were admitted to a post-acute outpatient service at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participation in PA was operationalized as the engagement in leisure-time PA for at least 150 min per week in the last 3 months. Self-rated health and measures of physical performance and muscle strength were assessed. Results-Mean age of 1846 participants was 55.2 ± 14.4 years and 47% were women. Before COVID-19, inactivity was detected in 47% of the whole study population; only 28% maintained pre-COVID-19 PA engagement. Inactivity was more frequent in women. The stopping of physical activity was associated with increased BMI and CRP levels, lower vitamin D levels and a higher prevalence of post-COVID-19 fatigue, dyspnea, arthralgia, and myalgia. Active participants had higher handgrip strength and performed better on both the six-minute walking test (6MWT) and at the one-minute sit-to-stand test (1MSTST). In particular, at the 6MWT, participants 65 and older that were still active after COVID-19 walked 32 m more than sedentary peers. Moreover, the distance covered was 28 m more than those who were active only before COVID-19 (p = 0.05). Formerly active subjects performed similarly at the 6MWT to inactive participants. PA was associated with better self-rated health. Conclusions-Our findings reveal that inactivity is frequent in the post-acute COVID-19 phase. Stopping physical activity after COVID-19 results in measures of performance that are comparable to those who were never active. Relevant differences in the distance covered at the 6MWT were found between older active subjects and their sedentary peers.}, } @article {pmid37047556, year = {2023}, author = {Hulme, J}, title = {COVID-19 and Diarylamidines: The Parasitic Connection.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047556}, issn = {1422-0067}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Post-Acute COVID-19 Syndrome ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System ; }, abstract = {As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of "post-COVID-19 syndrome" and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with 'post-COVID-19 syndrome' require investigation. This review begins with an overview of the parasitic-diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.}, } @article {pmid37046554, year = {2023}, author = {Coscia, F and Mancinelli, R and Gigliotti, PV and Checcaglini, F and Fanò-Illic, G}, title = {Physical Activity Effects on Muscle Fatigue in Sport in Active Adults with Long COVID-19: An Observational Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37046554}, issn = {2075-4418}, abstract = {Long COVID-19-related changes in physiology includes alterations in performing muscle work as fatigue. Data available do not allow us to define the usefulness of physical activity to attenuate long COVID-19 functional modifications. The present observational study investigates the effects of physical activity on the perception of fatigue, maximum power output, sleep, and cognitive modifications in subjects affected by long COVID-19, distinguishing between active and sedentary subjects. The data demonstrated the following: the perception of fatigue 1 year after the end of virus positivity was significantly reduced with respect to that observed after 6 months by more than 50% more in active subjects compared to sedentary ones; 6 months after the end of virus positivity, the force developed by active subjects was reduced (RM factor: p < 0.001, η2p = 0.527, post hoc: p < 0.001), but the reduction was more pronounced in sedentary ones (mean difference = 38.499 W); poor sleep quality and mild cognitive impairment were assessed in both active and sedentary subjects. In conclusion, the study suggests that the long COVID-19 fatigue was lower in active subjects respect to sedentary ones. A comparative analysis performed due to the overlap of functional alterations between long COVID-19 and ME/CFS showed that in a small percentage of the enrolled subjects (8%), the symptomatology reflected that of ME/CFS and was independent of the individual physical capacities.}, } @article {pmid37046498, year = {2023}, author = {Bajka, A and Muth, DR and Wiest, MRJ and Said, S and Rejdak, M and Sidhu, S and Foa, N and Blaser, F and Barthelmes, D and Toro, MD and Souied, EH and Deuel, JW and Schlagenhauf, P and Zweifel, SA}, title = {Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {7}, pages = {}, pmid = {37046498}, issn = {2075-4418}, abstract = {PURPOSE: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA).

METHODS: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l'Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant's eyes.

RESULTS: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group.

CONCLUSION: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02-0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues.}, } @article {pmid37046272, year = {2023}, author = {Müller, L and Di Benedetto, S}, title = {Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions.}, journal = {Immunity & ageing : I & A}, volume = {20}, number = {1}, pages = {17}, pmid = {37046272}, issn = {1742-4933}, abstract = {Advanced age is one of the significant risk determinants for coronavirus disease 2019 (COVID-19)-related mortality and for long COVID complications. The contributing factors may include the age-related dynamical remodeling of the immune system, known as immunosenescence and chronic low-grade systemic inflammation. Both of these factors may induce an inflammatory milieu in the aged brain and drive the changes in the microenvironment of neurons and microglia, which are characterized by a general condition of chronic inflammation, so-called neuroinflammation. Emerging evidence reveals that the immune privilege in the aging brain may be compromised. Resident brain cells, such as astrocytes, neurons, oligodendrocytes and microglia, but also infiltrating immune cells, such as monocytes, T cells and macrophages participate in the complex intercellular networks and multiple reciprocal interactions. Especially changes in microglia playing a regulatory role in inflammation, contribute to disturbing of the brain homeostasis and to impairments of the neuroimmune responses. Neuroinflammation may trigger structural damage, diminish regeneration, induce neuronal cell death, modulate synaptic remodeling and in this manner negatively interfere with the brain functions.In this review article, we give insights into neuroimmune interactions in the aged brain and highlight the impact of COVID-19 on the functional systems already modulated by immunosenescence and neuroinflammation. We discuss the potential ways of these interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and review proposed neuroimmune mechanisms and biological factors that may contribute to the development of persisting long COVID conditions. We summarize the potential mechanisms responsible for long COVID, including inflammation, autoimmunity, direct virus-mediated cytotoxicity, hypercoagulation, mitochondrial failure, dysbiosis, and the reactivation of other persisting viruses, such as the Cytomegalovirus (CMV). Finally, we discuss the effects of various interventional options that can decrease the propagation of biological, physiological, and psychosocial stressors that are responsible for neuroimmune activation and which may inhibit the triggering of unbalanced inflammatory responses. We highlight the modulatory effects of bioactive nutritional compounds along with the multimodal benefits of behavioral interventions and moderate exercise, which can be applied as postinfectious interventions in order to improve brain health.}, } @article {pmid37045862, year = {2023}, author = {Al-Kuraishy, HM and Al-Gareeb, AI and Alarfaj, SJ and Al-Akeel, RK and Faidah, H and El-Bouseary, MM and Sabatier, JM and De Waard, M and El-Masry, TA and Batiha, GE}, title = {Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5977}, pmid = {37045862}, issn = {2045-2322}, mesh = {Humans ; Male ; Adult ; Middle Aged ; *Erectile Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *COVID-19/complications ; Testosterone ; Luteinizing Hormone ; Follicle Stimulating Hormone ; }, abstract = {Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary-gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.}, } @article {pmid37044126, year = {2023}, author = {Asakura, T and Kimura, T and Kurotori, I and Kenichi, K and Hori, M and Hosogawa, M and Saijo, M and Nakanishi, K and Iso, H and Tamakoshi, A}, title = {Case-Control Study of Long COVID, Sapporo, Japan.}, journal = {Emerging infectious diseases}, volume = {29}, number = {5}, pages = {956-966}, pmid = {37044126}, issn = {1080-6059}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Japan/epidemiology ; Cross-Sectional Studies ; }, abstract = {We conducted a cross-sectional survey among SARS-CoV-2-positive persons and negative controls in Sapporo, Japan, to clarify symptoms of long COVID. We collected responses from 8,018 participants, 3,694 case-patients and 3,672 controls. We calculated symptom prevalence for case-patients at 2-3, 4-6, 7-9, 10-12, and 13-18 months after illness onset. We used logistic regression, adjusted for age and sex, to estimate the odds ratio (OR) for each symptom and control reference. We calculated symptom prevalence by stratifying for disease severity, age, and sex. At 4-18 months from illness onset, ORs for anosmia, ageusia, dyspnea, alopecia, and brain fog were consistently >1, whereas ORs for common cold-like, gastrointestinal, and dermatologic symptoms were <1. Time trend ORs increased for diminished ability to concentrate, brain fog, sleep disturbance, eye symptoms, and tinnitus. Clinicians should focus on systemic, respiratory, and neuropsychiatric symptoms among long COVID patients.}, } @article {pmid37041676, year = {2024}, author = {Zanini, G and Selleri, V and Roncati, L and Coppi, F and Nasi, M and Farinetti, A and Manenti, A and Pinti, M and Mattioli, AV}, title = {Reply to: Letter on the Recent Paper "Vascular 'Long COVID': A New Vessel Disease?".}, journal = {Angiology}, volume = {75}, number = {1}, pages = {99-100}, doi = {10.1177/00033197231170307}, pmid = {37041676}, issn = {1940-1574}, mesh = {Humans ; *COVID-19 ; *Vascular Diseases ; }, } @article {pmid37040829, year = {2023}, author = {Vera-Pineda, R and Carrizales-Sepúlveda, EF and Morales-Rendón, EJ and Ordaz-Farías, A and Solís, JG and Benavides-González, MA and Flores-Ramírez, R}, title = {Echocardiographic manifestations during the first 3 months after an episode of COVID-19 and their relationship with disease severity and persistence of symptoms.}, journal = {The American journal of the medical sciences}, volume = {366}, number = {1}, pages = {32-37}, pmid = {37040829}, issn = {1538-2990}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/diagnostic imaging ; Echocardiography ; Ventricular Function, Left ; Stroke Volume ; Patient Acuity ; }, abstract = {BACKGROUND: Cardiovascular manifestations in patients with COVID-19 are associated with dire outcomes. Long COVID syndrome is the persistence of symptoms after acute disease and is found in up to 40% of subjects. There is little information regarding subacute echocardiographic manifestations after COVID-19, and no study has included a Mexican mestizo population.

METHODS: This cross-sectional study included subjects older than 18 with an episode of COVID-19 in the last 3 months. Those with previously known cardiovascular disease were excluded. The patient´s medical history and COVID-19 information were obtained from clinical charts. We performed a transthoracic echocardiogram in every subject and determined left ventricular (LV) index mass, LV ejection fraction (LVEF), left ventricular global longitudinal strain (LV GLS), right ventricular (RV) GLS, and tricuspid annular plane systolic excursion (TAPSE). A descriptive and comparative analysis was performed based on symptom severity and persistence.

RESULTS: One hundred subjects were included; 63% were classified with mild and 37% with moderate to severe COVID-19. The median of LVEF was 60% (55-60), LV GLS and RV GLS was impaired in 34% and 74% of patients, respectively. Patients with moderate to severe disease had significantly lower LVEF (Mean Difference: -3.3), TAPSE (mean difference: -1.8), and higher (worse) LV GLS (Mean Difference: 2.5) and RV GLS (mean difference: 2.9). Persistent symptoms were associated with lower TAPSE and higher RVGLS.

CONCLUSIONS: Patients who recover from COVID-19 have a high prevalence of subtle RV and LV dysfunction using GLS analysis. A moderate to severe episode was associated with worse RV and LV function measured by RV GLS, TAPSE, and LV GLS. Subjects with persistent symptoms had worse RVGLS and TAPSE.}, } @article {pmid37039676, year = {2023}, author = {Kettunen, P and Lesnikova, A and Räsänen, N and Ojha, R and Palmunen, L and Laakso, M and Lehtonen, Š and Kuusisto, J and Pietiläinen, O and Saber, SH and Joensuu, M and Vapalahti, OP and Koistinaho, J and Rolova, T and Balistreri, G}, title = {SARS-CoV-2 Infection of Human Neurons Is TMPRSS2 Independent, Requires Endosomal Cell Entry, and Can Be Blocked by Inhibitors of Host Phosphoinositol-5 Kinase.}, journal = {Journal of virology}, volume = {97}, number = {4}, pages = {e0014423}, pmid = {37039676}, issn = {1098-5514}, mesh = {Humans ; Angiotensin-Converting Enzyme 2 ; *COVID-19/physiopathology ; Endosomes/metabolism/virology ; *Induced Pluripotent Stem Cells/metabolism ; Neurons/metabolism/virology ; Post-Acute COVID-19 Syndrome/physiopathology/virology ; *SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization/drug effects ; Phosphotransferases/antagonists & inhibitors ; Protein Kinase Inhibitors/pharmacology ; Astrocytes/virology ; Cells, Cultured ; }, abstract = {2019 coronavirus disease (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to respiratory illness, COVID-19 patients exhibit neurological symptoms lasting from weeks to months (long COVID). It is unclear whether these neurological manifestations are due to an infection of brain cells. We found that a small fraction of human induced pluripotent stem cell (iPSC)-derived neurons, but not astrocytes, were naturally susceptible to SARS-CoV-2. Based on the inhibitory effect of blocking antibodies, the infection seemed to depend on the receptor angiotensin-converting enzyme 2 (ACE2), despite very low levels of its expression in neurons. The presence of double-stranded RNA in the cytoplasm (the hallmark of viral replication), abundant synthesis of viral late genes localized throughout infected cells, and an increase in the level of viral RNA in the culture medium (viral release) within the first 48 h of infection suggested that the infection was productive. Productive entry of SARS-CoV-2 requires the fusion of the viral and cellular membranes, which results in the delivery of the viral genome into the cytoplasm of the target cell. The fusion is triggered by proteolytic cleavage of the viral surface spike protein, which can occur at the plasma membrane or from endosomes or lysosomes. We found that SARS-CoV-2 infection of human neurons was insensitive to nafamostat and camostat, which inhibit cellular serine proteases, including transmembrane serine protease 2 (TMPRSS2). Inhibition of cathepsin L also did not significantly block infection. In contrast, the neuronal infection was blocked by apilimod, an inhibitor of phosphatidyl-inositol 5 kinase (PIK5K), which regulates early to late endosome maturation. IMPORTANCE COVID-19 is a disease caused by the coronavirus SARS-CoV-2. Millions of patients display neurological symptoms, including headache, impairment of memory, seizures, and encephalopathy, as well as anatomical abnormalities, such as changes in brain morphology. SARS-CoV-2 infection of the human brain has been documented, but it is unclear whether the observed neurological symptoms are linked to direct brain infection. The mechanism of virus entry into neurons has also not been characterized. Here, we investigated SARS-CoV-2 infection by using a human iPSC-derived neural cell model and found that a small fraction of cortical-like neurons was naturally susceptible to infection. The productive infection was ACE2 dependent and TMPRSS2 independent. We also found that the virus used the late endosomal and lysosomal pathway for cell entry and that the infection could be blocked by apilimod, an inhibitor of cellular PIK5K.}, } @article {pmid37038664, year = {2023}, author = {Ray, SK and Mukherjee, S}, title = {Immunological Facet and Inception after Post-COVID-19 Vaccination.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {5}, pages = {e060423215496}, doi = {10.2174/1871526523666230406100146}, pmid = {37038664}, issn = {2212-3989}, mesh = {Humans ; *COVID-19 Vaccines/adverse effects ; *COVID-19/prevention & control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Disease Progression ; Vaccination ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) pandemic has produced an unparalleled setback for the world's economy and health. One of the best therapies to significantly lower severe illness and mortality from SARS-CoV-2 infection is vaccination. Worldwide vaccination campaigns are being implemented. New-onset autoimmune problems, such as immune thrombotic thrombocytopenia, autoimmune liver disorders, IgA nephropathy, Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, have recently been described more frequently after receiving COVID-19 vaccine. The creation of specific autoantibodies, molecular mimicry, and the function of specific vaccine adjuvants all emerge to play a significant role in autoimmunity. The post-acute sequelae of SARS-CoV-2, usually known as Long Covid Syndrome, are beginning to be better understood in terms of the disparities in immune responses seen in individuals with and without the condition. We anticipate that the knowledge gleaned from several COVID-19 investigations will be put to use in research on the inflammatory mechanisms implicated in serious and protracted illnesses, which is still a key unmet need.}, } @article {pmid37038497, year = {2023}, author = {Woo, MS and Mayer, C and Brehm, TT and Andersen, G and Weigel, A and Löwe, B and Lohse, AW and Addo, MM and Gerloff, C and Knobloch, JKM and Schulze Zur Wiesch, J and Friese, MA}, title = {Absence of self-reported neuropsychiatric and somatic symptoms after Omicron variant SARS-CoV-2 breakthrough infections.}, journal = {Brain communications}, volume = {5}, number = {2}, pages = {fcad092}, pmid = {37038497}, issn = {2632-1297}, abstract = {Persistent somatic and neuropsychiatric symptoms have been frequently described in patients after infection with severe acute respiratory syndrome coronavirus 2 even after a benign clinical course of the acute infection during the early phases of the coronavirus severe acute respiratory syndrome coronavirus 2 pandemic and are part of Long COVID. The Omicron variant emerged in November 2021 and has rapidly become predominant due to its high infectivity and suboptimal vaccine cross-protection. The frequency of neuropsychiatric post-acute sequelae after infection with the severe acute respiratory syndrome coronavirus 2 Omicron and adequate vaccination status is not known. Here, we aimed to characterize post-acute symptoms in individuals with asymptomatic or mildly symptomatic breakthrough infection with severe acute respiratory syndrome coronavirus 2. These individuals had either proven infection with the Omicron variant (n = 157) or their infection occurred in 2022 where Omicron was the predominant variant of severe acute respiratory syndrome coronavirus 2 in Germany (n = 107). This monocentric cross-sectional study was conducted at the University Medical Center Hamburg-Eppendorf between 11 February 2022 and 11 April 2022. We employed questionnaires addressing self-reported somatic symptom burden (Somatic Symptom Scale 8) and neuropsychiatric symptoms including mood (Patient Health Questionnaire 2), anxiety (Generalized Anxiety Disorder 7), attention (Mindful Attention Awareness Scale) and fatigue (Fatigue Assessment Scale) in a cohort of hospital workers. Scores were compared between 175 individuals less than 4 weeks after positive testing for severe acute respiratory syndrome coronavirus 2, 88 individuals more than 4 weeks after positive testing and 87 severe acute respiratory syndrome coronavirus 2 uninfected controls. The majority (n = 313; 89.5%) of included individuals were vaccinated at least three times. After recovery from infection, no significant differences in scores assessing neuropsychiatric and somatic symptoms were detected between the three groups (severe acute respiratory syndrome coronavirus 2 uninfected controls, individuals less and more than 4 weeks after positive testing) independent of age, sex, preconditions and vaccination status. In addition, self-reported symptom burden did not significantly correlate with the number of vaccinations against severe acute respiratory syndrome coronavirus 2, time from recovery or the number of infections. Notably, in all three groups, the mean scores for each item of our questionnaire lay below the pathological threshold. Our data show that persistent neuropsychiatric and somatic symptoms after recovery from severe acute respiratory syndrome coronavirus 2 infection in fully vaccinated hospital workers do not occur more frequently than that in uninfected individuals. This will guide healthcare professionals in the clinical management of patients after recovery from breakthrough infections with severe acute respiratory syndrome coronavirus 2.}, } @article {pmid37038445, year = {2023}, author = {Gietl, M and Burkert, F and Seiwald, S and Böhm, A and Hofer, S and Gostner, JM and Piater, T and Geisler, S and Weiss, G and Loeffler-Ragg, J and Sonnweber, T and Tancevski, I and Pizzini, A and Sahanic, S and Fuchs, D and Bellmann-Weiler, R and Kurz, K}, title = {Interferon-gamma Mediated Metabolic Pathways in Hospitalized Patients During Acute and Reconvalescent COVID-19.}, journal = {International journal of tryptophan research : IJTR}, volume = {16}, number = {}, pages = {11786469231154244}, pmid = {37038445}, issn = {1178-6469}, abstract = {BACKGROUND: Fatigue, sleep disturbance, and neurological symptoms during and after COVID-19 are common and might be associated with inflammation-induced changes in tryptophan (Trp) and phenylalanine (Phe) metabolism.

AIM: This pilot study investigated interferon gamma inducible biochemical pathways (namely Trp catabolism, neopterin, tyrosine [Tyr], and nitrite formation) during acute COVID-19 and reconvalescence.

PATIENTS AND METHODS: Thirty one patients with moderate to severe COVID-19 admitted to the University Hospital of Innsbruck in early 2020 (March-May) were followed up. Neurotransmitter precursors Trp, Phe, Tyr as well as kynurenine (Kyn), neopterin, nitrite, and routine laboratory parameters were analyzed during acute infection and at a follow-up (FU) 60 days thereafter. Clinical symptoms of patients (neurological symptoms, fatigue, sleep disturbance) were recorded and associations with concentrations of laboratory parameters investigated.

RESULTS AND CONCLUSION: Almost half of the patients suffered from neurological symptoms (48.4%), the majority of patients experienced sleep difficulties (56.7%) during acute COVID-19. Fatigue was present in nearly all patients. C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, Kyn, Phe concentrations were significantly increased, and Trp levels depleted during acute COVID-19. Patients with sleep impairment and neurological symptoms during acute illness presented with increased CRP and IL-6 concentrations, Trp levels were lower in patients with sleep disturbance. In general, inflammatory markers declined during reconvalescence. A high percentage of patients suffered from persistent symptoms at FU (neurological symptoms: 17.2%, fatigue: 51.7%, sleeping disturbance: 34.5%) and had higher CRP concentrations. Nitrite and Phe levels were lower in patients with sleeping difficulties at FU and Kyn/Trp ratio, as indicator of IDO activity, was significantly lower in patients with neurological symptoms compared to patients without them at FU. In summary, inflammation induced alterations of amino acid metabolism might be related to acute and persisting symptoms of COVID-19.}, } @article {pmid37037833, year = {2023}, author = {Ajčević, M and Iscra, K and Furlanis, G and Michelutti, M and Miladinović, A and Buoite Stella, A and Ukmar, M and Cova, MA and Accardo, A and Manganotti, P}, title = {Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5808}, pmid = {37037833}, issn = {2045-2322}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnostic imaging ; SARS-CoV-2 ; Magnetic Resonance Imaging/methods ; Neuroimaging/methods ; Brain/diagnostic imaging/blood supply ; Cerebrovascular Circulation/physiology ; Spin Labels ; }, abstract = {Cognitive impairment is one of the most prevalent symptoms of post Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) state, which is known as Long COVID. Advanced neuroimaging techniques may contribute to a better understanding of the pathophysiological brain changes and the underlying mechanisms in post-COVID-19 subjects. We aimed at investigating regional cerebral perfusion alterations in post-COVID-19 subjects who reported a subjective cognitive impairment after a mild SARS-CoV-2 infection, using a non-invasive Arterial Spin Labeling (ASL) MRI technique and analysis. Using MRI-ASL image processing, we investigated the brain perfusion alterations in 24 patients (53.0 ± 14.5 years, 15F/9M) with persistent cognitive complaints in the post COVID-19 period. Voxelwise and region-of-interest analyses were performed to identify statistically significant differences in cerebral blood flow (CBF) maps between post-COVID-19 patients, and age and sex matched healthy controls (54.8 ± 9.1 years, 13F/9M). The results showed a significant hypoperfusion in a widespread cerebral network in the post-COVID-19 group, predominantly affecting the frontal cortex, as well as the parietal and temporal cortex, as identified by a non-parametric permutation testing (p < 0.05, FWE-corrected with TFCE). The hypoperfusion areas identified in the right hemisphere regions were more extensive. These findings support the hypothesis of a large network dysfunction in post-COVID subjects with cognitive complaints. The non-invasive nature of the ASL-MRI method may play an important role in the monitoring and prognosis of post-COVID-19 subjects.}, } @article {pmid37037165, year = {2023}, author = {Espín, E and Yang, C and Shannon, CP and Assadian, S and He, D and Tebbutt, SJ}, title = {Cellular and molecular biomarkers of long COVID: a scoping review.}, journal = {EBioMedicine}, volume = {91}, number = {}, pages = {104552}, pmid = {37037165}, issn = {2352-3964}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Quality of Life ; Canada ; Biomarkers ; }, abstract = {BACKGROUND: Long-COVID (LC) encompasses diverse symptoms lasting months after the initial SARS-CoV-2 infection. Symptoms can be debilitating and affect the quality of life of individuals with LC and their families. Although the symptoms of LC are well described, the aetiology of LC remains unclear, and consequently, patients may be underdiagnosed. Identification of LC specific biomarkers is therefore paramount for the diagnosis and clinical management of the syndrome. This scoping review describes the molecular and cellular biomarkers that have been identified to date with potential use for diagnosis or prediction of LC.

METHODS: This review was conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews. A search was executed in the MEDLINE and EMBASE databases, as well as in the grey literature for original studies, published until October 5th, 2022, reporting biomarkers identified in participants with LC symptoms (from all ages, ethnicities, and sex), with a previous infection of SARS-CoV-2. Non-English studies, cross-sectional studies, studies without a control group, and pre-prints were excluded. Two reviewers independently evaluated the studies, extracted population data and associated biomarkers.

FINDINGS: 23 cohort studies were identified, involving 2163 LC patients [median age 51.8 years, predominantly female sex (61.10%), white (75%), and non-vaccinated (99%)]. A total of 239 candidate biomarkers were identified, consisting mainly of immune cells, immunoglobulins, cytokines, and other plasma proteins. 19 of the 239 candidate biomarkers identified were evaluated by the authors, by means of receiver operating characteristic (ROC) curves.

INTERPRETATION: Diverse cellular and molecular biomarkers for LC have been proposed. Validation of candidate biomarkers in independent samples should be prioritized. Modest reported performance (particularly in larger studies) suggests LC may encompass many distinct aetiologies, which should be explored e.g., by stratifying by symptom clusters and/or sex.

FUNDING: Dr. Tebbutt has received funding from the Canadian Institutes of Health Research (177747) to conduct this work. The funding source was not involved in this scoping review, or in the decision to submit this manuscript for publication.}, } @article {pmid37037045, year = {2023}, author = {Deschamps, T and Sauvaget, A}, title = {A Call to Immediate Action to Support Management of Long COVID Related-Symptoms.}, journal = {Alternative therapies in health and medicine}, volume = {29}, number = {3}, pages = {6}, pmid = {37037045}, issn = {1078-6791}, mesh = {Humans ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {No Abstract Available.}, } @article {pmid37036020, year = {2023}, author = {Barraclough, ML and Diaz-Martinez, JP and Knight, A and Bingham, K and Su, J and Kakvan, M and Grajales, CM and Tartaglia, MC and Ruttan, L and Wither, J and Choi, MY and Bonilla, D and Anderson, N and Appenzeller, S and Parker, B and Katz, P and Beaton, D and Green, R and Bruce, IN and Touma, Z}, title = {In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?.}, journal = {Lupus}, volume = {32}, number = {6}, pages = {737-745}, pmid = {37036020}, issn = {1477-0962}, mesh = {Humans ; United States ; *Lupus Erythematosus, Systemic/complications/psychology ; *Rheumatology ; Retrospective Studies ; Longitudinal Studies ; Pandemics ; *COVID-19/complications ; Cognition ; }, abstract = {OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification.

METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually.

RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person.

CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.}, } @article {pmid37034660, year = {2023}, author = {Buck, AM and Deitchman, AN and Takahashi, S and Lu, S and Goldberg, SA and Hoh, R and Williams, MC and Kerbleski, M and Deveau, TM and Munter, SE and Lombardo, J and Wrin, T and Petropoulos, CJ and Durstenfeld, MS and Hsue, PY and Kelly, JD and Greenhouse, B and Martin, JN and Deeks, SG and Peluso, MJ and Henrich, TJ}, title = {The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {37034660}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; K23 AI162249/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms.

METHODS: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes.

RESULTS: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants.

CONCLUSIONS: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses.}, } @article {pmid37034420, year = {2023}, author = {Porter, AL and Markley, M and Newman, N}, title = {The long COVID research literature.}, journal = {Frontiers in research metrics and analytics}, volume = {8}, number = {}, pages = {1149091}, pmid = {37034420}, issn = {2504-0537}, abstract = {While the COVID-19 pandemic morphs into less malignant forms, the virus has spawned a series of poorly understood, post-infection symptoms with staggering ramifications, i. e., long COVID (LC). This bibliometric study profiles the rapidly growing LC research domain [5,243 articles from PubMed and Web of Science (WoS)] to make its knowledge content more accessible. The article addresses What? Where? Who? and When? questions. A 13-topic Concept Grid presents bottom-up topic clusters. We break out those topics with other data fields, including disciplinary concentrations, topical details, and information on research "players" (countries, institutions, and authors) engaging in those topics. We provide access to results via a Dashboard website. We find a strongly growing, multidisciplinary LC research domain. That domain appears tightly connected based on shared research knowledge. However, we also observe notable concentrations of research activity in different disciplines. Data trends over 3 years of LC research suggest heightened attention to psychological and neurodegenerative symptoms, fatigue, and pulmonary involvement.}, } @article {pmid37034158, year = {2023}, author = {Yang, Z and Ma, Y and Bi, W and Tang, J}, title = {Exploring the research landscape of COVID-19-induced olfactory dysfunction: A bibliometric study.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1164901}, pmid = {37034158}, issn = {1662-4548}, abstract = {Since the outbreak of COVID-19, olfactory dysfunction (OD) has become an important and persistent legacy problem that seriously affects the quality of life. The purpose of this paper is to quantitatively analyze and visualize the current research status and development trend of COVID-19 related OD by using VOSviewer software. Based on the Web of Science database, a total of 1,592 relevant documents were retrieved in January 2023, with publication time spanning from 2020 to 2023. The bibliometric analysis revealed that the most influential research results in the field of COVID-19 related OD were concentrated in journals of related disciplines such as otorhinolaryngology, medicine, general and internal, virology, neurosciences, etc. The knowledge base of the research is mainly formed in two fields: COVID-19 clinical research and OD specialized research. The research hotspots are mainly concentrated in six directions: COVID-19, long COVID, smell, anosmia, OD, and recovery. Based on the results of the bibliometric analysis, the temporal trends of COVID-19 related OD studies were visually revealed, and relevant suggestions for future research were proposed.}, } @article {pmid37034080, year = {2023}, author = {Rodrigues, AN and Dias, ARN and Paranhos, ACM and Silva, CC and Bastos, TDR and de Brito, BB and da Silva, NM and de Sousa, EJS and Quaresma, JAS and Falcão, LFM}, title = {Headache in long COVID as disabling condition: A clinical approach.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1149294}, pmid = {37034080}, issn = {1664-2295}, abstract = {BACKGROUND AND PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can exacerbate previous headache disorders or change the type of pain experienced from headaches. This study aimed to investigate the clinical features of Long COVID headaches.

METHOD: This was a cross-sectional, descriptive, and analytical observational study that included 102 patients (with previous headache, n = 50; without previous headache, n = 52) with long COVID and headache complaints. The Migraine Disability Assessment Test and Visual Analog Pain Scale were used to collect participants' headache data according to a standardized protocol.

RESULTS: The patients in this study who reported experiencing headaches before COVID-19 had longer headache duration in the long COVID phase than that in the pre-long COVID phase (p = 0.031), exhibited partial improvement in headache symptoms with analgesics (p = 0.045), and had a duration of long COVID of <1 year (p = 0.030). Patients with moderate or severe disability and those classified as having severe headaches in the long COVID phase were highly likely to develop chronic headaches. Hospital admission [odds ratio (OR) = 3.0082; 95% confidence interval (95% CI): 1.10-8.26], back pain (OR = 4.0017; 95% CI: 1.13-14.17), insomnia (OR = 3.1339; 95% CI: 1.39-7.06), and paraesthesia (OR = 2.7600; 95% CI: 1.20-6.33) were associated with headache in these patients.

CONCLUSION: Headache is a disabling condition in patients with long COVID-19, exacerbating the conditions of those with headaches prior to contracting COVID-19.}, } @article {pmid37033176, year = {2023}, author = {Gräger, S and Pfirschke, R and Lorenz, M and Vilser, D and Krämer, M and Mentzel, HJ and Glutig, K}, title = {Lung ultrasound in children and adolescents with long-term effects of COVID-19: Initial results.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1112881}, pmid = {37033176}, issn = {2296-2360}, abstract = {INTRODUCTION: Chronic health effects following acute COVID-19 are increasingly observed as the pandemic continues and are grouped under long COVID. Although the acute course of the COVID disease is often milder, long COVID also affects children and adolescents. As the symptoms present in Long-COVID often seem to be non-specific and not limited to organ systems, clarification of the causes and the creation of a meaningful, efficient and targeted diagnostic algorithm is urgently needed.

METHODS: Therefore, in this prospective observational study, we examined 30 children with long COVID using lung ultrasound and compared the results with those of 15 lung-healthy children.

RESULTS: In our study, no significant difference was found between the two groups in the morphological criteria of lung ultrasound of the pleura or pleural lung structures. There was no significant correlation between the lung ultrasound findings and clinical Data.

DISCUSSION: Our findings are congruent with the current, albeit sparse, data. It is possible that the causes of persistent thoracic symptoms in long COVID might be more likely to be present in functional examinations, but not morphologically imageable. Nonspecific symptoms do not appear to be due to changes in the lung parenchyma. In conclusion, lung ultrasound alone and without baseline in acute disease is not suitable as a standard in the follow-up of long COVID patients. Further investigations on the morphological and functional changes in patient with long COVID is needed.}, } @article {pmid37032935, year = {2023}, author = {Taube, M}, title = {Depression and brain fog as long-COVID mental health consequences: Difficult, complex and partially successful treatment of a 72-year-old patient-A case report.}, journal = {Frontiers in psychiatry}, volume = {14}, number = {}, pages = {1153512}, pmid = {37032935}, issn = {1664-0640}, abstract = {SARS-CoV-2 (COVID-19) infection can result in long-term health consequences i.e., long COVID. The clinical manifestations of long COVID include depression, anxiety, brain fog with cognitive dysfunction, memory issues, and fatigue. These delayed effects of COVID-19 occur in up to 30% of people who have had an acute case of COVID-19. In this case report, a 72-year-old, fully vaccinated patient without pre-existing somatic or mental illnesses, or other relevant risk factors was diagnosed with long COVID. Nine months following an acute COVID-19 infection, the patient's depressive symptoms improved, but memory and concentration difficulties persisted, and the patient remains unable to resume work. These long-term symptoms are possibly linked to micro-hemorrhages detected during examinations of the patient's brain following COVID-19 infection. Patient treatment was complex, and positive results were attained via antidepressants and non-drug therapies e.g., art, music, drama, dance and movement therapy, physiotherapy, occupational therapy, and psychotherapy.}, } @article {pmid37031074, year = {2023}, author = {Martin de Francisco, Á and Fernández Fresnedo, G}, title = {Long COVID-19 renal disease: A present medical need for nephrology.}, journal = {Nefrologia}, volume = {43}, number = {1}, pages = {1-5}, pmid = {37031074}, issn = {2013-2514}, mesh = {Humans ; *Nephrology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Kidney Diseases/etiology/therapy ; SARS-CoV-2 ; }, } @article {pmid37030518, year = {2023}, author = {Quinn, KL and Lam, GY and Walsh, JF and Bhéreur, A and Brown, AD and Chow, CW and Chung, KYC and Cowan, J and Crampton, N and Décary, S and Falcone, EL and Graves, L and Gross, DP and Hanneman, K and Harvey, PJ and Holmes, S and Katz, GM and Parhizgar, P and Sharkawy, A and Tran, KC and Waserman, S and Zannella, VE and Cheung, AM}, title = {Cardiovascular Considerations in the Management of People With Suspected Long COVID.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {741-753}, pmid = {37030518}, issn = {1916-7075}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology/therapy ; Canada/epidemiology ; SARS-CoV-2 ; Heart ; }, abstract = {Approximately 15% of adult Canadians with SARS-CoV-2 infection develop lingering symptoms beyond 12 weeks after acute infection, known as post-COVID condition or long COVID. Some of the commonly reported long COVID cardiovascular symptoms include fatigue, shortness of breath, chest pain, and palpitations. Suspected long-term cardiovascular complications of SARS-CoV-2 infection might present as a constellation of symptoms that can be challenging for clinicians to diagnose and treat. When assessing patients with these symptoms, clinicians need to keep in mind myalgic encephalomyelitis/chronic fatigue syndrome, postexertional malaise and postexertional symptom exacerbation, dysautonomia with cardiac manifestations such as inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome, and occasionally mast cell activation syndrome. In this review we summarize the globally evolving evidence around management of cardiac sequelae of long COVID. In addition, we include a Canadian perspective, consisting of a panel of expert opinions from people with lived experience and experienced clinicians across Canada who have been involved in management of long COVID. The objective of this review is to offer some practical guidance to cardiologists and generalist clinicians regarding diagnostic and treatment approaches for adult patients with suspected long COVID who continue to experience unexplained cardiac symptoms.}, } @article {pmid37029655, year = {2024}, author = {Stern, B and Monteleone, P and Zoldan, J}, title = {SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks.}, journal = {Journal of biomedical materials research. Part A}, volume = {112}, number = {4}, pages = {524-533}, pmid = {37029655}, issn = {1552-4965}, support = {R01 HL157829/HL/NHLBI NIH HHS/United States ; R21 EB027812/EB/NIBIB NIH HHS/United States ; /HL/NHLBI NIH HHS/United States ; /EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; Spike Glycoprotein, Coronavirus ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Induced Pluripotent Stem Cells ; SARS-CoV-2 ; Hydrogels/pharmacology ; }, abstract = {With new daily discoveries about the long-term impacts of COVID-19, there is a clear need to develop in vitro models that can be used to better understand the pathogenicity and impact of COVID-19. Here, we demonstrate the utility of developing a model of endothelial dysfunction that utilizes human induced pluripotent stem cell-derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID-19 on the endothelium. These cells form capillary-like vasculature within 1 week after encapsulation and treating these cell-laden hydrogels with SARS-CoV-2 spike protein resulted in a significant decrease in the number of vessel-forming cells as well as vessel network connectivity quantified by our computational pipeline. This vascular dysfunction is a unique phenomenon observed upon treatment with SARS-CoV-2 SP and is not seen upon treatment with other coronaviruses, indicating that these effects were specific to SARS-CoV-2. We show that this vascular dysfunction is caused by an increase in inflammatory cytokines, associated with the COVID-19 cytokine storm, released from SARS-CoV-2 spike protein treated endothelial cells. Following treatment with the corticosteroid dexamethasone, we were able to prevent SARS-CoV-2 spike protein-induced endothelial dysfunction. Our results highlight the importance of understanding the interactions between SARS-CoV-2 spike protein and the endothelium and show that even in the absence of immune cells, the proposed 3D in vitro model for angiogenesis can reproduce COVID-19-induced endothelial dysfunction seen in clinical settings. This model represents a significant step in creating physiologically relevant disease models to further study the impact of long COVID and potentially identify mitigating therapeutics.}, } @article {pmid37029295, year = {2023}, author = {Arnsten, AFT and Ishizawa, Y and Xie, Z}, title = {Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.}, journal = {Molecular psychiatry}, volume = {28}, number = {11}, pages = {4540-4552}, pmid = {37029295}, issn = {1476-5578}, support = {R01 AG061190/AG/NIA NIH HHS/United States ; R01 AG041274/AG/NIA NIH HHS/United States ; R01 AG062509/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Calcium Signaling ; *Cognitive Dysfunction ; *Delirium ; Guanfacine/pharmacology/therapeutic use ; Neuroinflammatory Diseases ; Post-Acute COVID-19 Syndrome ; Prefrontal Cortex ; }, abstract = {Neuroinflammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This includes such challenging disorders as delirium, perioperative neurocognitive disorder, and the sustained cognitive deficits from "long-COVID" or traumatic brain injury. There are no FDA-approved treatments for these symptoms; thus, understanding their etiology is important for generating therapeutic strategies. The current review describes the molecular rationale for why PFC circuits are especially vulnerable to inflammation, and how α2A-adrenoceptor (α2A-AR) actions throughout the nervous and immune systems can benefit the circuits in PFC needed for higher cognition. The layer III circuits in the dorsolateral PFC (dlPFC) that generate and sustain the mental representations needed for higher cognition have unusual neurotransmission and neuromodulation. They are wholly dependent on NMDAR neurotransmission, with little AMPAR contribution, and thus are especially vulnerable to kynurenic acid inflammatory signaling which blocks NMDAR. Layer III dlPFC spines also have unusual neuromodulation, with cAMP magnification of calcium signaling in spines, which opens nearby potassium channels to rapidly weaken connectivity and reduce neuronal firing. This process must be tightly regulated, e.g. by mGluR3 or α2A-AR on spines, to prevent loss of firing. However, the production of GCPII inflammatory signaling reduces mGluR3 actions and markedly diminishes dlPFC network firing. Both basic and clinical studies show that α2A-AR agonists such as guanfacine can restore dlPFC network firing and cognitive function, through direct actions in the dlPFC, but also by reducing the activity of stress-related circuits, e.g. in the locus coeruleus and amygdala, and by having anti-inflammatory actions in the immune system. This information is particularly timely, as guanfacine is currently the focus of large clinical trials for the treatment of delirium, and in open label studies for the treatment of cognitive deficits from long-COVID.}, } @article {pmid37029117, year = {2023}, author = {Zang, C and Zhang, Y and Xu, J and Bian, J and Morozyuk, D and Schenck, EJ and Khullar, D and Nordvig, AS and Shenkman, EA and Rothman, RL and Block, JP and Lyman, K and Weiner, MG and Carton, TW and Wang, F and Kaushal, R}, title = {Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {1948}, pmid = {37029117}, issn = {2041-1723}, support = {K23 HL151876/HL/NHLBI NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Electronic Health Records ; SARS-CoV-2 ; Propensity Score ; }, abstract = {Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.}, } @article {pmid37027455, year = {2023}, author = {Zakia, H and Pradana, K and Iskandar, S}, title = {Risk factors for psychiatric symptoms in patients with long COVID: A systematic review.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0284075}, pmid = {37027455}, issn = {1932-6203}, mesh = {Adult ; Humans ; Female ; Aged ; Male ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *COVID-19/complications/epidemiology ; *Stress Disorders, Post-Traumatic/psychology ; Risk Factors ; }, abstract = {Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear. In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included. Several limitations in this review were the heterogeneity of studies' outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.}, } @article {pmid37027067, year = {2023}, author = {Tsuchida, T and Yoshimura, N and Ishizuka, K and Katayama, K and Inoue, Y and Hirose, M and Nakagama, Y and Kido, Y and Sugimori, H and Matsuda, T and Ohira, Y}, title = {Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {7}, pages = {3663-3670}, pmid = {37027067}, issn = {1591-9528}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cross-Sectional Studies ; Japan/epidemiology ; Fatigue/epidemiology ; }, abstract = {PURPOSE: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters.

METHODS: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal-Wallis test. Multiple comparison tests were performed using the Dunn's test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals.

RESULTS: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively.

CONCLUSIONS: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.}, } @article {pmid37025205, year = {2023}, author = {Serena, S and Deborah, P and Anja, F and Gwendolyn, G and Puhan, MA and Albanese, E}, title = {Association between serologically confirmed COVID-19 infection and cognitive functioning in community dwelling older adults.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1093852}, pmid = {37025205}, issn = {1664-2295}, abstract = {INTRODUCTION: COVID-19 infection can impact the central nervous system, and is often associated with cognitive decline. However, there are no studies linking serologically confirmed COVID-19 infection with objectively assessed cognitive functioning. We explored whether presence of SARS-CoV-2 antibodies account for variability in participants' scores on a neuropsychological assessment.

METHODS: In this cross-sectional study participants were 657 (mean age = 72.97; SD = 6.07 years; women = 47.7%) individuals randomly selected from the general population of the canton of Zurich and included in the Corona Immunitas study. We conducted serological tests between October 2020 and May 2021 to detect and quantify SARS-CoV-2 antibodies in peripheral venous blood samples. We assessed cognitive function, vaccination status (vaccinated; not vaccinated), number of health conditions, and demographic variables between January and August 2021. We studied the association between seropositivity and global cognitive function and five cognitive domains (language expression, language comprehension, temporal orientation, spatial orientation, and memory) with linear regression models. Based on SARS-CoV-2 antibodies and vaccination status, we stratified participants into three groups: No SARS-CoV-2 antibodies (N = 402); SARS-CoV-2 antibodies due to vaccination (N = 218); history of SARS-CoV-2 infection and no vaccination (N = 37).

RESULTS: In the regression model adjusted for age, sex, educational level, and number of health conditions, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to vaccination had better global cognitive functioning (Standardized beta = 0.10; 95% CI = 0.02; 0.17), and those with SARS-CoV-2 antibodies due to infection had poorer cognitive functioning (Standardized beta = -0.10; 95% CI = -0.18; -0.03). Regarding cognitive domains, compared to those without SARS-CoV-2 antibodies, those with SARS-CoV-2 antibodies due to infection scored more poorly on language comprehension and temporal orientation, and those with SARS-CoV-2 antibodies due to vaccination scored better on memory.

DISCUSSION: By linking serologically confirmed presence of SARS-CoV-2 antibodies to poorer global cognitive functioning in community dwelling older adults we strengthen existing evidence in support of cognitive decline related to COVID-19. Given the large number of infected older adults, and the endurance of the pandemic, our results highlight the need to address COVID-19 related cognitive decline in the clinical and public health areas of prevention, diagnosis, and treatment.}, } @article {pmid37025195, year = {2023}, author = {Dorobisz, K and Pazdro-Zastawny, K and Misiak, P and Kruk-Krzemień, A and Zatoński, T}, title = {Sensorineural Hearing Loss in Patients with Long-COVID-19: Objective and Behavioral Audiometric Findings.}, journal = {Infection and drug resistance}, volume = {16}, number = {}, pages = {1931-1939}, pmid = {37025195}, issn = {1178-6973}, abstract = {INTRODUCTION: The symptoms of COVID-19 are primarily respiratory system disorders. Sensorineural hearing loss can be caused by COVID-19, as other symptoms in the nervous system. Hearing loss may also be the only symptom or complication of this disease or the symptoms of long COVID-19. The study aimed to assess hearing in patients after COVID-19 infection.

MATERIAL AND METHODS: The study conducted ENT and full hearing assessment in COVID-19 infection. All patients underwent complete audiological diagnostics, including threshold tonal audiometry, tympanometry, otoacoustic emissions, and auditory brainstem evoked potentials (ABR) tests. The study group included 58 patients aged 23 to 75 years who were diagnosed with COVID-19 infection six months before inclusion in the present study and reported post-COVID-19 hearing impairment.

RESULTS: There were statistically significant differences between the control and study groups. Sensorineural hearing loss was found in 65.5% of the tonal audiometry test. The stapes reflex was absent in almost 20% of post-COVID-19 patients. The analysis of ABRs demonstrated longer latencies of wave III, V, and time intervals I-III, I-V in post-COVID-19 patients.

CONCLUSION: COVID-19 can damage the inner ear as well as the auditory pathway. Hearing loss may be the only symptom of COVID-19 or be a late complication of the disease due to postinfectious inflammation of the nerve tissue as a symptom of long COVID-19. Prolonged conduction of the auditory pathway shows the affinity of the virus to the nervous system as a symptom of long COVID. It is advisable to perform hearing diagnostics in patients after COVID-19 and provide them with specialist care.}, } @article {pmid37024626, year = {2023}, author = {Bertuccio, P and Degli Antoni, M and Minisci, D and Amadasi, S and Castelli, F and Odone, A and Quiros-Roldan, E}, title = {The impact of early therapies for COVID-19 on death, hospitalization and persisting symptoms: a retrospective study.}, journal = {Infection}, volume = {51}, number = {6}, pages = {1633-1644}, pmid = {37024626}, issn = {1439-0973}, mesh = {Female ; Male ; Humans ; *COVID-19 ; Secondary Prevention ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Antibodies, Monoclonal ; Antibodies, Viral ; Hospitalization ; Antiviral Agents/therapeutic use ; Ritonavir/therapeutic use ; }, abstract = {PURPOSE: Oral antivirals (nirmatrelvir/ritonavir and molnupiravir), intravenous short treatment of remdesivir and anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been used for early COVID-19 treatments in high risk of disease progression patients. The term long COVID has been used to refer to a range of new, returning, or ongoing symptoms after SARS-CoV-2 infection. Little is known about the impact of such therapies on long COVID.

METHODS: This is a retrospective observational study, including all outpatients evaluated from April 2021 to March 2022 in Brescia, Lombardy, northern Italy. Patients were stratified in three groups: (a) treated with mAbs, (b) treated with antivirals drugs and (c) controls (patients eligible for a or b who refused treatment). Data were collected at baseline and at month 1 and 3 (data on self-reported symptoms were collected using a telephone-administered questionnaire). We assessed early COVID-19 therapies effectiveness in preventing hospitalization, death at 1 or 3 months and persisting symptoms at 3 months after the onset of SARS-CoV-2 infection.

RESULTS: A total of 649 patients were included in the study, of which 242 (37.3%) were treated with mAbs, 197 (30.3%) with antiviral drugs and 210 (32.4%) were not treated. Patients most frequently reported cerebro-cardiovascular diseases (36.7%) followed by obesity (22%). Overall, 29 patients (4.5%) died or were hospitalized at 1 or 3-month follow-up. Death or hospitalization was positively associated with older ages, with a significant linear trend (OR 3.05; 95% CI 1.16-8.06, for patients aged 80 or more years compared to those aged less than 65). Data on long COVID at 3 months were available for 323 (49.8%) patients. A positive association emerged for females compared to men, with an OR of 2.14 (95% CI 1.30-3.53) for any symptoms. Conversely, inverse associations were found for treatment groups as compared to the control one, with significant estimates among patients treated with antiviral drugs for any symptoms (OR 0.43, 95% CI 0.21-0.87) and patients treated with mAbs for any neuro-behavioral symptoms (OR 0.48, 95% CI 0.25-0.92).

CONCLUSIONS: We report beneficial effect of early use of anti-SARS-CoV-2 antivirals and mAbs on long COVID.}, } @article {pmid37024311, year = {2023}, author = {Newlands, F and Rojas, NK and Nugawela, M and Pinto Pereira, SM and Buszewicz, M and Chalder, T and Cheung, EY and Dalrymple, E and Ford, T and Heyman, I and Ladhani, SN and McOwat, K and Simmons, R and Stephenson, T and Shafran, R}, title = {A Cross-Sectional Study of the Health of Emerging Young Adults in England Following a COVID-19 Infection.}, journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine}, volume = {73}, number = {1}, pages = {20-28}, pmid = {37024311}, issn = {1879-1972}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Adolescent ; Humans ; Young Adult ; *COVID-19 ; SARS-CoV-2 ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Quality of Life ; England/epidemiology ; }, abstract = {PURPOSE: This study describes long COVID symptomatology in a national sample of 18- to 20-year-olds with Polymerase Chain Reaction (PCR)-confirmed Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and matched test-negative controls in England. Symptoms in 18- to 20-year-olds were compared to symptoms in younger adolescents (aged 11-17 years) and all adults (18+).

METHODS: A national database was used to identify SARS-CoV-2 PCR-positive 18- to 20-year-olds and test-negative controls matched by time of test, age, gender, and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included children and young people with long COVID and REal-time Assessment of Community Transmission studies.

RESULTS: Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive; 440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%; 35.7%), shortness of breath (28.8%; 16.3%), and headaches (13.7%; 12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18- to 20-year-olds, there was no significant difference in health-related quality of life and well-being (p > .05). However, test-positives reported being significantly more tired than test-negatives (p = .04).

DISCUSSION: Seven months after PCR test, a high proportion of test-positive and test-negative 18- to 20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts.}, } @article {pmid37024264, year = {2023}, author = {Hansen, CB and Dvoncova, K and Pérez-Alós, L and Fogh, K and Madsen, JR and Garred, CH and Jarlhelt, I and Nielsen, PB and Petersen, SS and Fjordager, CG and Lauritsen, KT and Hilsted, L and Boding, L and Iversen, KK and Hyveled, L and Garred, P}, title = {SARS-CoV-2 antibody dynamics over time and risk factors associated with infection and long COVID-19 symptoms in large working environments.}, journal = {Journal of internal medicine}, volume = {293}, number = {6}, pages = {763-781}, doi = {10.1111/joim.13637}, pmid = {37024264}, issn = {1365-2796}, mesh = {Humans ; Male ; Adolescent ; Young Adult ; Adult ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; Seroepidemiologic Studies ; Working Conditions ; Antibodies, Viral ; Risk Factors ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; }, abstract = {BACKGROUND: Factors influencing SARS-CoV-2 antibody dynamics, transmission, waning and long COVID-19 symptomatology are still not fully understood.

METHODS: In the Danish section of the Novo Nordisk Group, we performed a prospective seroepidemiological study during the first and second waves of the COVID-19 pandemic. All employees and their household members (>18 years) were invited to participate in a baseline (June-August 2020), 6-month follow-up (December 2020-January 2021), and 12-month follow-up (August 2021) sampling. In total, 18,614 accepted and provided at least one blood sample and completed a questionnaire regarding socioeconomic background, health status, previous SARS-CoV-2 infection, and persistent symptoms. Total antibody and specific IgM, IgG and IgA levels against recombinant receptor binding domain were tested.

RESULTS: At baseline, the SARS-CoV-2-antibody seroprevalence was 3.9%. At 6-month follow-up, the seroprevalence was 9.1%, while at 12-month follow-up, the seroprevalence was 94.4% (after the vaccine roll-out). Male sex and younger age (18-40 years) were significant risk factors for seropositivity. From baseline to the 6-month sampling, we observed a substantial waning of IgM, IgG and IgA levels (p < 0.001), regardless of age, sex and initial antibody level. An increased antibody level was found in individuals infected prior to vaccination compared to vaccinated infection naïves (p < 0.0001). Approximately a third of the seropositive individuals reported one or more persistent COVID-19 symptoms, with anosmia and/or ageusia (17.5%) and fatigue (15.3%) being the most prevalent.

CONCLUSION: The study provides a comprehensive insight into SARS-CoV-2 antibody seroprevalence following infection and vaccination, waning, persistent COVID-19 symptomatology and risk factors for seropositivity in large working environments.}, } @article {pmid37024137, year = {2023}, author = {Thompson, S}, title = {Employers must provide better support to workers with long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {381}, number = {}, pages = {800}, doi = {10.1136/bmj.p800}, pmid = {37024137}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37020492, year = {2023}, author = {Chow, JSF and D'Souza, A and Ford, M and Marshall, S and San Miguel, S and Parameswaran, A and Parsons, M and Ramirez, J and Teramayi, R and Maurya, N}, title = {A descriptive study of the clinical impacts on COVID-19 survivors using telemonitoring (The TeleCOVID Study).}, journal = {Frontiers in medical technology}, volume = {5}, number = {}, pages = {1126258}, pmid = {37020492}, issn = {2673-3129}, abstract = {BACKGROUND: There is increasing evidence that COVID-19 survivors are at increased risk of experiencing a wide range of cardiovascular complications post infection; however, there are no validated models or clear guidelines for remotely monitoring the cardiac health of COVID-19 survivors.

OBJECTIVE: This study aims to test a virtual, in-home healthcare monitoring model of care for detection of clinical symptoms and impacts on COVID-19 survivors. It also aims to demonstrate system usability and feasibility.

METHODS: This open label, prospective, descriptive study was conducted in South Western Sydney. Included in the study were patients admitted to the hospital with the diagnosis of COVID-19 between June 2021 and November 2021. Eligible participants after consent were provided with a pulse oximeter to measure oxygen saturation and a S-Patch EX to monitor their electrocardiogram (ECG) for a duration of 3 months. Data was transmitted in real-time to a mobile phone via Bluetooth technology and results were sent to the study team via a cloud-based platform. All the data was reviewed in a timely manner by the investigator team, for post COVID-19 related symptoms, such as reduction in oxygen saturation and arrhythmia.

OUTCOME MEASURE: This study was designed for feasibility in real clinical setting implementation, enabling the study team to develop and utilise a virtual, in-home healthcare monitoring model of care to detect post COVID-19 clinical symptoms and impacts on COVID-19 survivors.

RESULTS: During the study period, 23 patients provided consent for participation. Out of which 19 patients commenced monitoring. Sixteen patients with 81 (73.6%) valid tests were included in the analysis and amongst them seven patients were detected by artificial intelligence to have cardiac arrhythmias but not clinically symptomatic. The patients with arrhythmias had a higher occurrence of supraventricular ectopy, and most of them took at least 2 tests before detection. Notably, patients with arrhythmia had significantly more tests than those without [t-test, t (13) = 2.29, p < 0.05].

CONCLUSIONS: Preliminary observations have identified cardiac arrhythmias on prolonged cardiac monitoring in 7 out of the first 16 participants who completed their 3 months follow-up. This has allowed early escalation to their treating doctors for further investigations and early interventions.}, } @article {pmid37020190, year = {2023}, author = {Warren-Gash, C and Lacey, A and Cook, S and Stocker, D and Toon, S and Lelii, F and Ford, B and Ireland, G and Ladhani, SN and Stephenson, T and Nguipdop-Djomo, P and Mangtani, P and , }, title = {Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {201}, pmid = {37020190}, issn = {1471-2334}, mesh = {Child ; Humans ; Adolescent ; Middle Aged ; *COVID-19 ; Anosmia ; Pandemics ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear.

METHODS: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection.

RESULTS: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test.

CONCLUSIONS: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.}, } @article {pmid37020055, year = {2023}, author = {Percze, AR and Nagy, A and Polivka, L and Barczi, E and Czaller, I and Kovats, Z and Varga, JT and Ballai, JH and Muller, V and Horvath, G}, title = {Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms.}, journal = {Inflammopharmacology}, volume = {31}, number = {6}, pages = {2819-2825}, pmid = {37020055}, issn = {1568-5608}, mesh = {Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sleep Quality ; Sleepiness ; Retrospective Studies ; *COVID-19/complications ; Fatigue/complications/epidemiology ; }, abstract = {Acute infections with SARS-CoV-2 variants of concerns (VOCs) differ in clinical presentation. Discrepancies in their long-term sequelae, commonly referred to as long COVID, however, remain to be explored. We retrospectively analyzed data of 287 patients presented at the post-COVID care of the Pulmonology Department, Semmelweis University, Budapest, Hungary, and infected with SARS-CoV-2 during a period of 3 major epidemic waves in Hungary (February-July 2021, VOC: B.1.1.7, Alpha, N = 135; August-December 2021, VOC: B.1.617.2, Delta, N = 89; and January-June 2022, VOC: B.1.1.529, Omicron; N = 63), > 4 weeks after acute COVID-19. Overall, the ratio of long COVID symptomatic (LC) and asymptomatic (NS) patients was 2:1. Self-reported questionnaires on fatigue (Fatigue Severity Scale, FSS), sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) showed higher scores for LC (4.79 ± 0.12, 7.45 ± 0.33 and 7.46 ± 0.27, respectively) than NS patients (2.85 ± 0.16, 5.23 ± 0.32 and 4.26 ± 0.29, respectively; p < 0.05 for all vs. LC). By comparing data of the three waves, mean FSS and PSQI scores of LC patients, but not ESS scores, exceeded the normal range in all, with no significant inter-wave differences. Considering FSS ≥ 4 and PSQI > 5 cutoff values, LC patients commonly exhibited problematic fatigue (≥ 70%) and poor sleep quality (> 60%) in all three waves. Comparative analysis of PSQI component scores of LC patients identified no significant differences between the three waves. Our findings highlight the importance of concerted efforts to manage both fatigue and sleep disturbances in long COVID patient care. This multifaceted approach should be followed in all cases infected with either VOCs of SARS-CoV-2.}, } @article {pmid37019821, year = {2023}, author = {Sykes, RA and Neves, KB and Alves-Lopes, R and Caputo, I and Fallon, K and Jamieson, NB and Kamdar, A and Legrini, A and Leslie, H and McIntosh, A and McConnachie, A and Morrow, A and McFarlane, RW and Mangion, K and McAbney, J and Montezano, AC and Touyz, RM and Wood, C and Berry, C}, title = {Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.}, journal = {European heart journal. Cardiovascular pharmacotherapy}, volume = {9}, number = {4}, pages = {371-386}, pmid = {37019821}, issn = {2055-6845}, support = {RE/13/5/30177/BHF_/British Heart Foundation/United Kingdom ; PG/19/28/34310/BHF_/British Heart Foundation/United Kingdom ; COV/GLA/20/05/CSO_/Chief Scientist Office/United Kingdom ; PG/17/25/32884/BHF_/British Heart Foundation/United Kingdom ; CH/12/4/29762/BHF_/British Heart Foundation/United Kingdom ; COV/LTE/20/10/CSO_/Chief Scientist Office/United Kingdom ; RE/18/6/34217/BHF_/British Heart Foundation/United Kingdom ; MR/S018905/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Female ; Middle Aged ; Male ; rho-Associated Kinases/metabolism ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; *Cardiovascular Diseases/diagnosis/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {BACKGROUND: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise.

METHODS AND RESULTS: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8-71.7]; picrosirius red 68.6% [95% CI: 64.4-72.8]} vs. controls [MT 64.9% (95% CI: 59.4-70.3) (P = 0.028); picrosirius red 60.1% (95% CI: 55.4-64.8), (P = 0.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9-49.3) vs. controls (10.0%; 95% CI: 4.4-15.6) (P < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated.

CONCLUSION: Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.}, } @article {pmid37019065, year = {2023}, author = {Oliveira, LA and Lucchetta, RC and Mendes, AM and Bonetti, AF and Xavier, CS and Sanches, ACC and Borba, HHL and Oliota, AFR and Rossignoli, P and Mastroianni, PC and Venson, R and Virtuoso, S and de Nadai, TR and Wiens, A}, title = {Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.}, journal = {Value in health regional issues}, volume = {36}, number = {}, pages = {34-43}, pmid = {37019065}, issn = {2212-1102}, mesh = {Humans ; Male ; Aged ; Female ; Brazil/epidemiology ; *COVID-19/epidemiology ; Overweight ; Post-Acute COVID-19 Syndrome ; Hospitalization ; Hospitals, Public ; Cost of Illness ; }, abstract = {OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives.

METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission.

RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively.

CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.}, } @article {pmid37018291, year = {2023}, author = {Gomes, SMR and Brito, ACS and Manfro, WFP and Ribeiro-Alves, M and Ribeiro, RSA and da Cal, MS and Lisboa, VDC and Abreu, DPB and Castilho, LDR and Porto, LCMS and Mafort, TT and Lopes, AJ and da Silva, SAG and Dutra, PML and Rodrigues, LS}, title = {High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients.}, journal = {PloS one}, volume = {18}, number = {4}, pages = {e0283983}, pmid = {37018291}, issn = {1932-6203}, mesh = {Humans ; Adolescent ; *Cytokines ; SARS-CoV-2 ; Interleukin-10 ; *COVID-19 ; COVID-19 Testing ; Chemokine CXCL10 ; Cross-Sectional Studies ; Interleukin-2 ; Interleukin-6 ; Interleukin-8 ; Post-Acute COVID-19 Syndrome ; Brazil ; Interferon-gamma ; Tumor Necrosis Factor-alpha ; }, abstract = {BACKGROUND: Cytokines induced by SARS-CoV-2 infection play a crucial role in the pathophysiology of COVID-19 and hyperinflammatory responses have been associated with poor clinical outcomes, with progression to severe conditions or long-term subacute complications named as long-COVID-19.

METHODS: In this cross-sectional study, we aimed to evaluate a set of antigen-specific inflammatory cytokines in blood from recovered COVID-19 individuals or who suffered a post-acute phase of SARS-CoV-2 infection compared to healthy individuals with no history of COVID-19 exposition or infection. Interferon-gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), tumor necrosis factor (TNF), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-17A were quantified by multiplex cytometric bead assay and enzyme-linked immunosorbent assay after stimulation of whole blood with recombinant Spike protein from SARS-CoV-2. Additionally, all participants have evaluated for anti-(S) protein-specific IgG antibodies. Clinical specimens were collected within two months of COVID-19 diagnosis.

RESULTS: A total of 47 individuals were enrolled in the study, a median age of 43 years (IQR = 14.5), grouped into healthy individuals with no history of infection or exposure to SARS-CoV-2 (unexposed group; N = 21); and patients from the Health Complex of the Rio de Janeiro State University (UERJ), Brazil, who were SARS-CoV-2 positive by RT-PCR (COVID-19 group)-categorized as recovered COVID-19 (N = 11) or long-COVID-19 (N = 15). All COVID-19 patients presented at least one signal or symptom during the first two weeks of infection. Six patients were hospitalized and required invasive mechanical ventilation. Our results showed that COVID-19 patients had significantly higher levels of IFN-γ, TNF, IL-1β, IL-2, IL-6, IL-8, and IP-10 than the unexposed group. The long-COVID-19 group has presented significantly high levels of IL-1β and IL-6 compared to unexposed individuals, but not from recovered COVID-19. A principal-component analysis demonstrated 84.3% of the total variance of inflammatory-SARS-CoV-2 response in the first two components, and it was possible to stratify IL-6, TNF, IL-1β, IL-10, and IL-2 as the top-five cytokines which are candidates to discriminate COVID-19 group (including long-COVID-19 subgroup) and healthy unexposed individuals.

CONCLUSION: We revealed important S protein-specific differential biomarkers in individuals affected by COVID-19, bringing new insights into the inflammatory status or SARS-CoV-2 exposition determination.}, } @article {pmid37018063, year = {2023}, author = {Bowen, R and Arany, PR}, title = {Use of either transcranial or whole-body photobiomodulation treatments improves COVID-19 brain fog.}, journal = {Journal of biophotonics}, volume = {16}, number = {8}, pages = {e202200391}, doi = {10.1002/jbio.202200391}, pmid = {37018063}, issn = {1864-0648}, mesh = {Humans ; Brain ; *COVID-19/therapy ; Electroencephalography ; *Low-Level Light Therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is increasing recognition of post-COVID-19 sequelae involving chronic fatigue and brain fog, for which photobiomodulation (PBM) therapy has been utilized. This open-label, pilot, human clinical study examined the efficacy of two PBM devices, for example, a helmet (1070 nm) for transcranial (tPBM) and a light bed (660 and 850 nm) for whole body (wbPBM), over a 4-week period, with 12 treatments for two separate groups (n = 7 per group). Subjects were evaluated with a neuropsychological test battery, including the Montreal Cognitive Assessment (MoCA), the digit symbol substitution test (DSST), the trail-making tests A and B, the physical reaction time (PRT), and a quantitative electroencephalography system (WAVi), both pre- and post- the treatment series. Each device for PBM delivery was associated with significant improvements in cognitive tests (p < 0.05 and beyond). Changes in WAVi supported the findings. This study outlines the benefits of utilizing PBM therapy (transcranial or whole-body) to help treat long-COVID brain fog.}, } @article {pmid37016218, year = {2023}, author = {Oberhofer, E}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {165}, number = {7}, pages = {19}, doi = {10.1007/s15006-023-2552-5}, pmid = {37016218}, issn = {1613-3560}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid37016158, year = {2023}, author = {Graham, F}, title = {Daily briefing: Concerns about exercise as a treatment for long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-023-00986-2}, pmid = {37016158}, issn = {1476-4687}, } @article {pmid37015258, year = {2023}, author = {Jie Chee, Y and Dalan, R}, title = {Repurposing exercise training and pharmacological therapies to address the post-acute sequelae of COVID-19 (PASC) in diabetes mellitus.}, journal = {Diabetes research and clinical practice}, volume = {199}, number = {}, pages = {110651}, pmid = {37015258}, issn = {1872-8227}, mesh = {Humans ; *COVID-19 ; *Diabetes Mellitus/drug therapy ; Disease Progression ; }, } @article {pmid37013139, year = {2023}, author = {Sarkis, Y and Saleem, N and Vuppalanchi, R and Gromski, M}, title = {COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis.}, journal = {Hepatic medicine : evidence and research}, volume = {15}, number = {}, pages = {27-32}, pmid = {37013139}, issn = {1179-1535}, abstract = {The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease.}, } @article {pmid37012954, year = {2023}, author = {Kadir, M and Ahmad, T and Bass, J}, title = {Post-COVID Sequelae: From Lung Disease to Long Disease.}, journal = {Cureus}, volume = {15}, number = {3}, pages = {e35668}, pmid = {37012954}, issn = {2168-8184}, abstract = {COVID-19 can have both an acute phase and post-acute phase of illness termed post-COVID sequelae, or "long Covid." In this case, a 66-year-old woman with a past medical history of reactive airway disease was admitted for shortness of breath twice. The first episode occurred in the setting of active COVID-19 infection. However, the second episode took place seven weeks later in the absence of COVID-19 as evidenced by a rapid antigen test. It is unclear why she re-developed shortness of breath after being discharged symptom-free from her initial admission. After treatment with prednisone, albuterol, and ipratropium she experienced symptomatic relief yet again and outpatient pulmonary function testing demonstrated a mildly obstructive pattern reversed with an inhaled bronchodilator. She has remained symptom-free since finishing an outpatient prednisone course. It is possible she developed post-COVID sequelae resembling an acute asthma exacerbation. Though the exact mechanism of post-COVID sequelae is not known, it is thought to be due to a combination of immune activation, dysregulation, and suppression. It is an important presentation for internists to know given the prevalence of COVID-19.}, } @article {pmid37011639, year = {2023}, author = {Howe, S and Szanyi, J and Blakely, T}, title = {The health impact of long COVID during the 2021-2022 Omicron wave in Australia: a quantitative burden of disease study.}, journal = {International journal of epidemiology}, volume = {52}, number = {3}, pages = {677-689}, pmid = {37011639}, issn = {1464-3685}, mesh = {Humans ; *Life Expectancy ; Quality-Adjusted Life Years ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; SARS-CoV-2 ; *COVID-19/epidemiology ; Global Health ; Australia/epidemiology ; Cost of Illness ; }, abstract = {BACKGROUND: Long COVID symptoms occur for a proportion of acute COVID-19 survivors, with reduced risk among the vaccinated and for Omicron compared with Delta variant infections. The health loss attributed to pre-Omicron long COVID has previously been estimated using only a few major symptoms.

METHODS: The years lived with disability (YLDs) due to long COVID in Australia during the 2021-22 Omicron BA.1/BA.2 wave were calculated using inputs from previously published case-control, cross-sectional or cohort studies examining the prevalence and duration of individual long COVID symptoms. This estimated health loss was compared with acute SARS-CoV-2 infection YLDs and years of life lost (YLLs) from SARS-CoV-2. The sum of these three components equals COVID-19 disability-adjusted life years (DALYs); this was compared with DALYs from other diseases.

RESULTS: A total of 5200 [95% uncertainty interval (UI) 2200-8300] YLDs were attributable to long COVID and 1800 (95% UI 1100-2600) to acute SARS-CoV-2 infection, suggesting long COVID caused 74% of the overall YLDs from SARS-CoV-2 infections in the BA.1/BA.2 wave. Total DALYs attributable to SARS-CoV-2 were 50 900 (95% UI 21 000-80 900), 2.4% of expected DALYs for all diseases in the same period.

CONCLUSION: This study provides a comprehensive approach to estimating the morbidity due to long COVID. Improved data on long COVID symptoms will improve the accuracy of these estimates. As data accumulate on SARS-CoV-2 infection sequelae (e.g. increased cardiovascular disease rates), total health loss is likely to be higher than estimated in this study. Nevertheless, this study demonstrates that long COVID requires consideration in pandemic policy planning, given it is responsible for the majority of direct SARS-CoV-2 morbidity, including during an Omicron wave in a highly vaccinated population.}, } @article {pmid37006590, year = {2023}, author = {Aguayo, GA and Fischer, A and Elbéji, A and Linn, N and Ollert, M and Fagherazzi, G}, title = {Association between use of psychotropic medications prior to SARS-COV-2 infection and trajectories of COVID-19 recovery: Findings from the prospective Predi-COVID cohort study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1055440}, pmid = {37006590}, issn = {2296-2565}, mesh = {Male ; Adult ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {Psychological disturbances are frequent following COVID-19. However, there is not much information about whether pre-existing psychological disorders are associated with the severity and evolution of COVID-19. We aimed to explore the associations between regular psychotropic medication use (PM) before infection as a proxy for mood or anxiety disorders with COVID-19 recovery trajectories. We used data from the Predi-COVID study. We followed adults, tested positive for SARS-CoV-2 and collected demographics, clinical characteristics, comorbidities and daily symptoms 14 days after inclusion. We calculated a score based on 16 symptoms and modeled latent class trajectories. We performed polynomial logistic regression with PM as primary exposure and the different trajectories as outcome. We included 791 participants, 51% were men, and 5.3% reported regular PM before infection. We identified four trajectories characterizing recovery dynamics: "Almost asymptomatic," "Quick recovery," "Slow recovery," and "Persisting symptoms". With a fully adjusted model for age, sex, socioeconomic, lifestyle and comorbidity, we observed associations between PM with the risks of being in more severe trajectories than "Almost Asymptomatic": "Quick recovery" (relative risk (95% confidence intervals) 3.1 (2.7, 3.4), "Slow recovery" 5.2 (3.0, 9.2), and "Persisting symptoms"11.7 (6.9, 19.6) trajectories. We observed a gradient of risk between PM before the infection and the risk of slow or no recovery in the first 14 days. These results suggest that a pre-existing psychological condition increases the risk of a poorer evolution of COVID-19 and may increase the risk of Long COVID. Our findings can help to personalize the care of people with COVID-19.}, } @article {pmid37005767, year = {2023}, author = {Glassman, I and Le, N and Mirhosseini, M and Alcantara, CA and Asif, A and Goulding, A and Muneer, S and Singh, M and Robison, J and Guilford, F and Venketaraman, V}, title = {The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {28}, number = {3}, pages = {59}, pmid = {37005767}, issn = {2768-6698}, support = {R15 HL143545/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/prevention & control ; Thromboinflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Glutathione/therapeutic use ; }, abstract = {Immunothrombosis has emerged as a dominant pathological process exacerbating morbidity and mortality in acute- and long-COVID-19 infections. The hypercoagulable state is due in part to immune system dysregulation, inflammation and endothelial cell damage, as well as a reduction in defense systems. One defense mechanism in particular is glutathione (GSH), a ubiquitously found antioxidant. Evidence suggests that reduction in GSH increases viral replication, pro-inflammatory cytokine release, and thrombosis, as well as decreases macrophage-mediated fibrin removal. The collection of adverse effects as a result of GSH depletion in states like COVID-19 suggest that GSH depletion is a dominant mechanism of immunothrombosis cascade. We aim to review the current literature on the influence of GSH on COVID-19 immunothrombosis pathogenesis, as well as the beneficial effects of GSH as a novel therapeutic for acute- and long-COVID-19.}, } @article {pmid37005013, year = {2023}, author = {Dell'Imperio, SG and Aboul-Hassan, D and Batchelor, R and Chambers-Peeple, K and Clauw, DJ and DeJonckheere, M and Bergmans, RS}, title = {Vaccine perceptions among Black adults with long COVID.}, journal = {Ethnicity & health}, volume = {28}, number = {6}, pages = {853-873}, pmid = {37005013}, issn = {1465-3419}, support = {T32 AR007080/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; Adult ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Reinfection ; *COVID-19/prevention & control ; *Vaccines ; }, abstract = {OBJECTIVES: Low uptake of COVID vaccines within Black communities is a concern given the stark racial inequities associated with the pandemic. Prior research details COVID vaccine perceptions within the general population and Black communities specifically. However, Black individuals with long COVID may be more or less receptive to future COVID vaccination than their peers without long COVID. The impact of COVID vaccination on long COVID symptoms is still controversial, since some studies suggest that vaccination can improve long COVID symptoms, whereas other studies report no significant change in symptoms or a worsening of symptoms. In this study, we aimed to characterize the factors influencing perceptions of COVID vaccines among Black adults with long COVID to inform future vaccine-related policies and interventions.

DESIGN: We conducted 15 semi-structured, race-concordant interviews over Zoom with adults who reported physical or mental health symptoms that lingered for a month or more after acute COVID infection. We transcribed and anonymized the interviews and implemented inductive, thematic analysis to identify factors influencing COVID vaccine perceptions and the vaccine decision-making process.

RESULTS: We identified five themes that influenced vaccine perceptions: (1) Vaccine safety and efficacy; (2) Social implications of vaccination status; (3) Navigating and interpreting vaccine-related information; (4) Possibility of abuse and exploitation by the government and scientific community; and (5) Long COVID status. Safety concerns were amplified by long COVID status and mistrust in social systems due to mistreatment of the Black community.

CONCLUSIONS: Among the factors influencing COVID vaccine perceptions, participants reported a desire to avoid reinfection and a negative immune response. As COVID reinfection and long COVID become more common, achieving adequate uptake of COVID vaccines and boosters may require approaches that are tailored in partnership with the long COVID patient community.}, } @article {pmid37004544, year = {2023}, author = {Peron, JPS}, title = {Direct and indirect impact of SARS-CoV-2 on the brain.}, journal = {Human genetics}, volume = {142}, number = {8}, pages = {1317-1326}, pmid = {37004544}, issn = {1432-1203}, support = {2020/06145-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2017/26170-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 316646/2021-0//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Brain ; *Brain Diseases ; }, abstract = {Although COVID-19 is mostly a pulmonary disease, it is now well accepted that it can cause a much broader spectrum of signs and symptoms and affect many other organs and tissue. From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and health care practitioners. Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, after 2 years of pandemic, the chronic impact observed during long-COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic, and mild diseased patients may evolve with important neurological and psychiatric symptoms, as confusion, memory loss, cognitive decline, chronic fatigue, associated or not with anxiety and depression. Thus, the knowledge on the correlation between COVID-19 and the central nervous system is of great relevance. In this sense, here we discuss some important mechanisms obtained from in vitro and in vivo investigation regarding how SARS-CoV-2 impacts the brain and its cells and function.}, } @article {pmid37004143, year = {2023}, author = {Chang, CH and Chen, SJ and Chen, YC and Tsai, HC}, title = {A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.}, journal = {The American journal of case reports}, volume = {24}, number = {}, pages = {e938732}, pmid = {37004143}, issn = {1941-5923}, mesh = {Female ; Humans ; Adult ; *Sleep Initiation and Maintenance Disorders/etiology/therapy ; Depression/etiology ; Transcranial Magnetic Stimulation ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Anxiety/etiology ; Prefrontal Cortex/physiology ; *Cognitive Dysfunction/etiology ; }, abstract = {BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.}, } @article {pmid37003610, year = {2023}, author = {Soriano, JB and González, J and Torres, A}, title = {Panta rhei (Πάντα ῥεῖ), or everything flows with long COVID.}, journal = {The European respiratory journal}, volume = {61}, number = {4}, pages = {}, doi = {10.1183/13993003.02490-2022}, pmid = {37003610}, issn = {1399-3003}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19 ; }, } @article {pmid37002390, year = {2023}, author = {Fairbank, R}, title = {Long COVID exercise trials proposed by NIH raise alarm.}, journal = {Nature}, volume = {616}, number = {7956}, pages = {228-229}, pmid = {37002390}, issn = {1476-4687}, mesh = {Humans ; *National Institutes of Health (U.S.)/economics/organization & administration ; *Post-Acute COVID-19 Syndrome/therapy ; *Research Support as Topic/methods/organization & administration ; United States ; *Exercise Therapy/adverse effects ; *Clinical Trials as Topic ; }, } @article {pmid37001283, year = {2023}, author = {Elhadad, S and Redmond, D and Tan, A and Huang, J and Rodriguez, BL and Racine-Brzostek, SE and Subrahmanian, S and Ahamed, J and Laurence, J}, title = {Defibrotide mitigates endothelial cell injury induced by plasmas from patients with COVID-19 and related vasculopathies.}, journal = {Thrombosis research}, volume = {225}, number = {}, pages = {47-56}, pmid = {37001283}, issn = {1879-2472}, mesh = {Humans ; Caspase 8 ; *COVID-19/complications ; *Vascular Diseases ; Endothelial Cells ; *Hematopoietic Stem Cell Transplantation ; Anticoagulants ; }, abstract = {BACKGROUND AND OBJECTIVES: COVID-19 progression is characterized by systemic small vessel arterial and venous thrombosis. Microvascular endothelial cell (MVEC) activation and injury, platelet activation, and histopathologic features characteristic of acute COVID-19 also describe certain thrombotic microangiopathies, including atypical hemolytic-uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and hematopoietic stem cell transplant (HSCT)-associated veno-occlusive disease (VOD). We explored the effect of clinically relevant doses of defibrotide, approved for HSCT-associated VOD, on MVEC activation/injury.

METHODS: Human dermal MVEC were exposed to plasmas from patients with acute TMAs or acute COVID-19 in the presence and absence of defibrotide (5μg/ml) and caspase 8, a marker of EC activation and apoptosis, was assessed. RNAseq was used to explore potential mechanisms of defibrotide activity.

RESULTS: Defibrotide suppressed TMA plasma-induced caspase 8 activation in MVEC (mean 60.2 % inhibition for COVID-19; p = 0.0008). RNAseq identified six major cellular pathways associated with defibrotide's alteration of COVID-19-associated MVEC changes: TNF-α signaling; IL-17 signaling; extracellular matrix (ECM)-EC receptor and platelet receptor interactions; ECM formation; endothelin activity; and fibrosis. Communications across these pathways were revealed by STRING analyses. Forty transcripts showing the greatest changes induced by defibrotide in COVID-19 plasma/MVEC cultures included: claudin 14 and F11R (JAM), important in maintaining EC tight junctions; SOCS3 and TNFRSF18, involved in suppression of inflammation; RAMP3 and transgelin, which promote angiogenesis; and RGS5, which regulates caspase activation and apoptosis.

CONCLUSION: Our data, in the context of a recent clinical trial in severe COVID-19, suggest benefits to further exploration of defibrotide and these pathways in COVID-19 and related endotheliopathies.}, } @article {pmid37000609, year = {2023}, author = {Nandadeva, D and Skow, RJ and Stephens, BY and Grotle, AK and Georgoudiou, S and Barshikar, S and Seo, Y and Fadel, PJ}, title = {Cardiovascular and cerebral vascular health in females with postacute sequelae of COVID-19.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {324}, number = {6}, pages = {H713-H720}, pmid = {37000609}, issn = {1522-1539}, mesh = {Humans ; Female ; *Hyperemia ; Pulse Wave Analysis ; *COVID-19/complications ; Blood Pressure ; Vasodilator Agents/pharmacology ; Brachial Artery ; *Vascular Stiffness ; }, abstract = {Many individuals who had coronavirus disease 2019 (COVID-19) develop detrimental persistent symptoms, a condition known as postacute sequelae of COVID-19 (PASC). Despite the elevated risk of cardiovascular disease following COVID-19, limited studies have examined vascular function in PASC with equivocal results reported. Moreover, the role of PASC symptom burden on vascular health has not been examined. We tested the hypothesis that peripheral and cerebral vascular function would be blunted and central arterial stiffness would be elevated in patients with PASC compared with age-matched controls. Furthermore, we hypothesized that impairments in vascular health would be greater in those with higher PASC symptom burden. Resting blood pressure (BP; brachial and central), brachial artery flow-mediated dilation (FMD), forearm reactive hyperemia, carotid-femoral pulse wave velocity (PWV), and cerebral vasodilator function were measured in 12 females with PASC and 11 age-matched female controls without PASC. The severity of persistent symptoms in those with PASC was reported on a scale of 1-10 (higher score: greater severity). Brachial BP (e.g., systolic BP, 126 ± 19 vs.109 ± 8 mmHg; P = 0.010), central BP (P < 0.050), and PWV (7.1 ± 1.2 vs. 6.0 ± 0.8 m/s; P = 0.015) were higher in PASC group compared with controls. However, FMD, reactive hyperemia, and cerebral vasodilator function were not different between groups (P > 0.050 for all). Total symptom burden was not correlated with any measure of cardiovascular health (P > 0.050 for all). Collectively, these findings indicate that BP and central arterial stiffness are elevated in females with PASC, whereas peripheral and cerebral vascular function appear to be unaffected, effects that appear independent of symptom burden.NEW & NOTEWORTHY We demonstrate for the first time that resting blood pressure (BP) and central arterial stiffness are higher in females with PASC compared with controls. In contrast, peripheral and cerebral vascular functions appear unaffected. Moreover, there was no relationship between total PASC symptom burden and measures of BP, arterial stiffness, or vascular function. Collectively, these findings suggest that females with PASC could be at greater risk of developing hypertension, which appears independent of symptom burden.}, } @article {pmid37000135, year = {2023}, author = {Riepl, M}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 2: Manifestations of Infection, Nomenclature, Transmission, and Treatment.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {2}, pages = {98-107}, pmid = {37000135}, issn = {1092-4221}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {Described by some authors as a "black swan event . . . likened to the economic scene of World War Two," the effects of coronavirus-disease-2019 (COVID-19) and attempted techniques for its prevention and treatment have presented medical, economic, social, and (often) politicized challenges on a global scale. Caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is, in many patients, associated with severe morbidity and mortality during the first few weeks after infection. At the time of this writing, estimates indicate that up to 70% of survivors may also experience "long COVID," a condition that can persist for weeks, months, or years after virus-free status has been achieved, often produces severe symptoms across multiple organ systems, and can result in a wide variety of adverse outcomes. Scientific knowledge about COVID-19 and long COVID continues to evolve at a rate insufficient to address the protean manifestations and effects of continually emerging novel SARS-CoV-2 variants. When the recovery of afflicted patients is further challenged by intolerance to ingredients in (or available doses or dosage forms of) commercially manufactured medications that could provide therapeutic support, customized formulations may offer relief and enable healing. In this article, COVID-19 is addressed as an entity (i.e., the pandemic crisis it engendered is summarized to date, the most common signs and symptoms of that disease are described, and the phenomenon of cytokine storm in infected patients is examined), SARS-CoV-2 is discussed (i.e., common nomenclature systems used to describe and track that virus are presented and the processes of viral transmission, mechanisms of action, replication, and recombination are briefly reviewed), and the efficacy of a currently underappreciated agent (low-dose naltrexone) for the treatment of COVID-19 is considered. Two compounded formulations that can be used to treat the signs, symptoms, and/or sequelae of acute COVID-19 and/or long COVID are provided for easy reference.}, } @article {pmid36998202, year = {2023}, author = {Hammarström, P and Nyström, S}, title = {Viruses and amyloids - a vicious liaison.}, journal = {Prion}, volume = {17}, number = {1}, pages = {82-104}, pmid = {36998202}, issn = {1933-690X}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Viruses ; *Virus Diseases/complications ; Amyloid ; Viral Proteins ; }, abstract = {The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet. The evolutionary driving forces that dictate protein amyloid formation propensity are different for viruses compared to prokaryotes and eukaryotes, while posttranslational endoproteolysis appears to be a common mechanism leading up to amyloid formation for both viral and human proteins. Not only do human and viral proteins form amyloid irrespective of each other but there are also several examples of co-operativity between amyloids, viruses and the inter-, and intra-host spread of the respective entity. Abnormal blood clotting in severe and long COVID and as a side effect in some vaccine recipients has been connected to amyloid formation of both the human fibrin and the viral Spike-protein. We conclude that there are many intersects between viruses and amyloids and, consequently, amyloid and virus research need to join forces here. We emphasize the need to accelerate development and implementation in clinical practice of antiviral drugs to preclude PAS and downstream neurological damage. There is also an ample need for retake on suitable antigen targets for the further development of next generation of vaccines against the current and coming pandemics.}, } @article {pmid36997975, year = {2023}, author = {Turner, GM and McMullan, C and Aiyegbusi, OL and Hughes, SE and Walker, A and Jeyes, F and Adler, Y and Chong, A and Buckland, L and Stanton, D and Davies, EH and Haroon, S and Calvert, M}, title = {Co-production of a feasibility trial of pacing interventions for Long COVID.}, journal = {Research involvement and engagement}, volume = {9}, number = {1}, pages = {18}, pmid = {36997975}, issn = {2056-7529}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: The high incidence of COVID-19 globally has led to a large prevalence of Long COVID but there is a lack of evidence-based treatments. There is a need to evaluate existing treatments for symptoms associated with Long COVID. However, there is first a need to evaluate the feasibility of undertaking randomised controlled trials of interventions for the condition. We aimed to co-produce a feasibility study of non-pharmacological interventions to support people with Long COVID.

METHODS: A consensus workshop on research prioritisation was conducted with patients and other stakeholders. This was followed by the co-production of the feasibility trial with a group of patient partners, which included the design of the study, the selection of interventions, and the production of dissemination strategies.

RESULTS: The consensus workshop was attended by 23 stakeholders, including six patients. The consensus from the workshop was to develop a clinical trial platform that focused on testing different pacing interventions and resources. For the co-production of the feasibility trial, patient partners selected three pacing resources to evaluate (video, mobile application, and book) and co-designed feasibility study processes, study materials and undertook usability testing of the digital trial platform.

CONCLUSION: In conclusion, this paper reports the principles and process used to co-produce a feasibility study of pacing interventions for Long COVID. Co-production was effective and influenced important aspects of the study.}, } @article {pmid36997265, year = {2023}, author = {Saunders, C and Sperling, S and Bendstrup, E}, title = {Concerns regarding a suggested long COVID paradigm - Authors' reply.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {4}, pages = {e36-e37}, doi = {10.1016/S2213-2600(23)00087-5}, pmid = {36997265}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid36997264, year = {2023}, author = {Cornish, F and Stelson, EA}, title = {Concerns regarding a suggested long COVID paradigm.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {4}, pages = {e35}, doi = {10.1016/S2213-2600(23)00095-4}, pmid = {36997264}, issn = {2213-2619}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36997263, year = {2023}, author = {van der Palen, J}, title = {Concerns regarding a suggested long COVID paradigm.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {4}, pages = {e34}, doi = {10.1016/S2213-2600(23)00088-7}, pmid = {36997263}, issn = {2213-2619}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36997262, year = {2023}, author = {Schwendinger, F and Knaier, R and Schmidt-Trucksäss, A}, title = {Concerns regarding a suggested long COVID paradigm.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {4}, pages = {e33}, pmid = {36997262}, issn = {2213-2619}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36995436, year = {2023}, author = {Fedorchenko, Y and Zimba, O}, title = {Long COVID in autoimmune rheumatic diseases.}, journal = {Rheumatology international}, volume = {43}, number = {7}, pages = {1197-1207}, pmid = {36995436}, issn = {1437-160X}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Autoimmune Diseases/complications ; *Rheumatic Diseases/drug therapy ; }, abstract = {Consequences of Corona Virus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) are clinically diverse. SARS-CoV-2 infection has been associated with various autoimmune and rheumatic manifestations over the past three years. Emerging evidence points to the possibility of Long COVID predisposition in rheumatic patients due to the changes in immune regulatory response. The aim of this article was to overview data on the pathobiology of Long COVID in patients with RDs. Related risk factors, clinical characteristics, and prognosis of Long COVID in RDs were analyzed. Relevant articles were retrieved from Medline/PubMed, Scopus, and Directory of Open Access Journals (DOAJ). Diverse mechanisms of viral persistence, chronic low-grade inflammation, lasting production of autoantibodies, endotheliopathy, vascular complications, and permanent tissue damage have been described in association with Long COVID. Patients with RDs who survive COVID-19 often experience severe complications due to the immune disbalance resulting in multiple organ damage. Regular monitoring and treatment are warranted in view of the accumulating evidence.}, } @article {pmid36995412, year = {2023}, author = {Freidin, MB and Cheetham, N and Duncan, EL and Steves, CJ and Doores, KJ and Malim, MH and Rossi, N and Lord, JM and Franks, PW and Borsini, A and Granville Smith, I and Falchi, M and Pariante, C and Williams, FMK}, title = {Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {72}, number = {5}, pages = {947-953}, pmid = {36995412}, issn = {1420-908X}, support = {G108/603/MRC_/Medical Research Council/United Kingdom ; MR/J002739/1/MRC_/Medical Research Council/United Kingdom ; MR/N029488/1/MRC_/Medical Research Council/United Kingdom ; MR/T004142/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Interleukin-6 ; *Fatigue Syndrome, Chronic/epidemiology ; Pandemics ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {OBJECTIVE AND DESIGN: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is the major symptom of the post-COVID syndrome (known colloquially as long-COVID). The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19.

SUBJECTS AND METHODS: We analyzed pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19-positive and -negative participants were categorized based on SARS-CoV-2 antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale.

RESULTS: COVID-19-positive participants exhibited mild disease. Chronic fatigue was a prevalent symptom among this population and significantly higher in positive vs. negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in positive and negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in negative, but not positive individuals. Raised BMI was associated with chronic fatigue in positive participants.

CONCLUSIONS: Pre-existing increased IL-6 levels may contribute to chronic fatigue symptoms, but there was no increased risk in individuals with mild COVID-19 compared with uninfected individuals. Elevated BMI also increased the risk of chronic fatigue in mild COVID-19, consistent with previous reports.}, } @article {pmid36995291, year = {2024}, author = {Krishna, N and K P, S and G K, R}, title = {Identifying diseases associated with Post-COVID syndrome through an integrated network biology approach.}, journal = {Journal of biomolecular structure & dynamics}, volume = {42}, number = {2}, pages = {652-671}, doi = {10.1080/07391102.2023.2195003}, pmid = {36995291}, issn = {1538-0254}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Nervous System Diseases ; *Neoplasms ; Biology ; }, abstract = {A growing body of research shows that COVID-19 is now recognized as a multi-organ disease with a wide range of manifestations that can have long-lasting repercussions, referred to as post-COVID-19 syndrome. It is unknown why the vast majority of COVID-19 patients develop post-COVID-19 syndrome, or why patients with pre-existing disorders are more likely to experience severe COVID-19. This study used an integrated network biology approach to obtain a comprehensive understanding of the relationship between COVID-19 and other disorders. The approach involved building a PPI network with COVID-19 genes and identifying highly interconnected regions. The molecular information contained within these subnetworks, as well as the pathway annotations, were used to reveal the link between COVID-19 and other disorders. Using Fisher's exact test and disease-specific gene information, significant COVID-19-disease associations were discovered. The study discovered diseases that affect multiple organs and organ systems, thus proving the theory of multiple organ damage caused by COVID-19. Cancers, neurological disorders, hepatic diseases, cardiac disorders, pulmonary diseases, and hypertensive diseases are just a few of the conditions linked to COVID-19. Pathway enrichment analysis of shared proteins revealed the shared molecular mechanism of COVID-19 and these diseases. The findings of the study shed new light on the major COVID-19-associated disease conditions and how their molecular mechanisms interact with COVID-19. The novelty of studying disease associations in the context of COVID-19 provides new insights into the management of rapidly evolving long-COVID and post-COVID syndromes, which have significant global implications.Communicated by Ramaswamy H. Sarma.}, } @article {pmid36994036, year = {2022}, author = {Bhat, S and Dsouza, AMP and Suresh, S}, title = {Post-vaccination COVID-19 infection among health care workers in a medical college hospital.}, journal = {Journal of family medicine and primary care}, volume = {11}, number = {12}, pages = {7882-7885}, pmid = {36994036}, issn = {2249-4863}, abstract = {INTRODUCTION: The world witnessed the pandemic of coronavirus disease (COVID)-19, caused by the virus Severe acute respiratory syndrome coronavirus 2, wreaking havoc on all our lives. The healthcare sector in India was faced with numerous challenges and struggles. The health care workers of this developing country risked everything against this pandemic, which put them at a higher risk of transmission of this infection. The risk of contracting Covid infection was not nullified, even though vaccination was introduced and was made available to these healthcare workers at the earliest. Hence this study aimed to understand the severity of COVID-19 infection, post covid vaccination.

MATERIALS AND METHODS: A cross-sectional study was conducted among 95 health care workers of Father Muller Medical College hospital who were infected with COVID-19, post their vaccination. A validated preformed questionnaire was used to collect the data from the participants. Data were analyzed using IBM SPSS 21[st] version. Descriptive statistics were used. A value of P < 0.05 was considered significant.

RESULTS: In our study, 34.7% of health care workers required hospital admission for COVID-19 treatment. The mean duration is taken by health care workers to return to work after COVID was 12.59 days (SD-4.43). The severity of COVID-19 infection was significantly higher among females, the younger population, and the nursing cadre.

CONCLUSION: The severity of COVID-19 infection among health care workers and long COVID can be reduced by timely vaccination.}, } @article {pmid36994024, year = {2022}, author = {Rao, CM and Behera, D and Mohapatra, AK and Mohapatra, SK and Jagaty, SK and Banu, P and Pattanaik, AP and Mohapatra, I and Patro, S}, title = {Supervised hospital based pulmonary rehabilitation outcome in long COVID-experience from a tertiary care hospital.}, journal = {Journal of family medicine and primary care}, volume = {11}, number = {12}, pages = {7875-7881}, pmid = {36994024}, issn = {2249-4863}, abstract = {INTRODUCTION: Some patients suffer from various multisystem symptoms even after active process of COVID-19 illness has settled lasting more than four weeks called as long COVID. Pulmonary rehabilitation therapy is the proposed option in those patients. This study aims to study the impact of pulmonary rehabilitation on outcome of long COVID patients through improvement in mMRC dyspnea scale, oxygen saturation, cough score, six-minute walk distance and biomarkers of inflammation.

MATERIALS AND METHODS: A retrospective observational study was carried out from the data of electronic medical records among 71 Long COVID patients. Parameters like Spo2, MMRC scale, cough score, six-minute walking distance along with blood levels of D-dimer, C-reactive protein (CRP), leucocyte count at the time of admission and after three weeks of pulmonary rehabilitation were collected. The outcome among the patients was divided into full recovery and partial recovery group. Statistical analysis was done using SPSS software version 19.0.

RESULT: Among 71 cases in our study 60 (84.50%) where male with mean age was 52.7 ± 13.23 years. Biomarkers like CRP and d-Dimer were elevated in 68 (95.7%) and 48 (67.6%) patients, respectively, at the time of admission. After 3 weeks of pulmonary rehabilitation mean SPO2, cough score, 6MWD showed significant improvement and normalization of biomarkers in recovered group of 61 out of 71 which was statistically significant.

CONCLUSION: Significant improvement of oxygen saturation, mMRC grade, cough score, six-minute walk distance and normalization of biomarkers were marked following pulmonary rehabilitation. Thus, pulmonary rehabilitation therapy should be offered to all long COVID cases.}, } @article {pmid36993423, year = {2023}, author = {Gressett, TE and Leist, SR and Ismael, S and Talkington, G and Dinnon, KH and Baric, RS and Bix, G}, title = {Mouse Adapted SARS-CoV-2 Model Induces "Long-COVID" Neuropathology in BALB/c Mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.18.533204}, pmid = {36993423}, issn = {2692-8205}, abstract = {The novel coronavirus SARS-CoV-2 has caused significant global morbidity and mortality and continues to burden patients with persisting neurological dysfunction. COVID-19 survivors develop debilitating symptoms to include neuro-psychological dysfunction, termed "Long COVID", which can cause significant reduction of quality of life. Despite vigorous model development, the possible cause of these symptoms and the underlying pathophysiology of this devastating disease remains elusive. Mouse adapted (MA10) SARS-CoV-2 is a novel mouse-based model of COVID-19 which simulates the clinical symptoms of respiratory distress associated with SARS-CoV-2 infection in mice. In this study, we evaluated the long-term effects of MA10 infection on brain pathology and neuroinflammation. 10-week and 1-year old female BALB/cAnNHsd mice were infected intranasally with 10 [4] plaque-forming units (PFU) and 10 [3] PFU of SARS-CoV-2 MA10, respectively, and the brain was examined 60 days post-infection (dpi). Immunohistochemical analysis showed a decrease in the neuronal nuclear protein NeuN and an increase in Iba-1 positive amoeboid microglia in the hippocampus after MA10 infection, indicating long-term neurological changes in a brain area which is critical for long-term memory consolidation and processing. Importantly, these changes were seen in 40-50% of infected mice, which correlates to prevalence of LC seen clinically. Our data shows for the first time that MA10 infection induces neuropathological outcomes several weeks after infection at similar rates of observed clinical prevalence of "Long COVID". These observations strengthen the MA10 model as a viable model for study of the long-term effects of SARS-CoV-2 in humans. Establishing the viability of this model is a key step towards the rapid development of novel therapeutic strategies to ameliorate neuroinflammation and restore brain function in those suffering from the persistent cognitive dysfunction of "Long-COVID".}, } @article {pmid36992491, year = {2023}, author = {Van der Feltz-Cornelis, CM and Moriarty, AS and Strain, WD}, title = {Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder.}, journal = {Viruses}, volume = {15}, number = {3}, pages = {}, pmid = {36992491}, issn = {1999-4915}, support = {/WT_/Wellcome Trust/United Kingdom ; 204829/WT_/Wellcome Trust/United Kingdom ; COV-LT2-0043/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Conversion Disorder/diagnosis/psychology ; *Nervous System Diseases/diagnosis/therapy ; }, abstract = {There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently. FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective. Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.}, } @article {pmid36992454, year = {2023}, author = {Motta, CS and Torices, S and da Rosa, BG and Marcos, AC and Alvarez-Rosa, L and Siqueira, M and Moreno-Rodriguez, T and Matos, ADR and Caetano, BC and Martins, JSCC and Gladulich, L and Loiola, E and Bagshaw, ORM and Stuart, JA and Siqueira, MM and Stipursky, J and Toborek, M and Adesse, D}, title = {Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling.}, journal = {Viruses}, volume = {15}, number = {3}, pages = {}, pmid = {36992454}, issn = {1999-4915}, support = {MH128022, MH122235, MH072567, HL126559, DA044579, DA039576, DA040537, DA050528, R01HL126559-06S1 , DA047157/NH/NIH HHS/United States ; R01 MH128022/MH/NIMH NIH HHS/United States ; R01 DA044579/DA/NIDA NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; P30 AI073961/AI/NIAID NIH HHS/United States ; R01 DA039576/DA/NIDA NIH HHS/United States ; R01 DA050528/DA/NIDA NIH HHS/United States ; R01 DA040537/DA/NIDA NIH HHS/United States ; R21 MH122235/MH/NIMH NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *NF-kappa B/metabolism ; SARS-CoV-2/metabolism ; Endothelial Cells/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Brain ; Blood-Brain Barrier ; Mitochondria/metabolism ; }, abstract = {Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood-brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.}, } @article {pmid36992322, year = {2023}, author = {Cusi, MG and Di Giacomo, AM and Anichini, G and Gori Savellini, G and Terrosi, C and Gandolfo, C and Maio, M}, title = {Rational Use of Monoclonal Antibodies as Therapeutic Treatment in an Oncologic Patient with Long COVID.}, journal = {Viruses}, volume = {15}, number = {3}, pages = {}, pmid = {36992322}, issn = {1999-4915}, mesh = {Humans ; Male ; Aged ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Melanoma ; SARS-CoV-2 ; *Skin Neoplasms ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral/therapeutic use ; }, abstract = {We present the case of a 76-year-old male patient persistently infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the setting of a stage IIIC cutaneous melanoma and non-Hodgkin's lymphoma (NHL). Due to the persistent coronavirus disease 19 (COVID-19), all cancer treatments were discontinued. Because of the worsening of his clinical state and the persistence of SARS-CoV-2 positivity for more than six months, the patient was treated with sotrovimab, which was ineffective due to resistance mutations acquired during that time. In order to resume cancer treatment and make the patient free from SARS-CoV-2, an in vitro screening of Evusheld monoclonal antibodies (tixagevumab-cilgavimab) against the viral strains isolated from the subject was performed. The promising results obtained during in vitro testing led to the authorization of the off-label use of Evusheld, which made the patient negative for SARS-CoV-2, thus, allowing him to resume his cancer treatment. This study highlights the Evusheld monoclonal antibodies' efficacy, not only in prevention but also in successful therapy against prolonged COVID-19. Therefore, testing neutralizing monoclonal antibodies in vitro against SARS-CoV-2 mutants directly isolated from patients could provide useful information for the treatment of people affected by long COVID.}, } @article {pmid36992283, year = {2023}, author = {Dhawan, M and Rabaan, AA and Alwarthan, S and Alhajri, M and Halwani, MA and Alshengeti, A and Najim, MA and Alwashmi, ASS and Alshehri, AA and Alshamrani, SA and AlShehail, BM and Garout, M and Al-Abdulhadi, S and Al-Ahmed, SH and Thakur, N and Verma, G}, title = {Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.}, journal = {Vaccines}, volume = {11}, number = {3}, pages = {}, pmid = {36992283}, issn = {2076-393X}, abstract = {The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.}, } @article {pmid36992274, year = {2023}, author = {Lippke, S and Rinn, R and Derksen, C and Dahmen, A}, title = {Patients' Post-/Long-COVID Symptoms, Vaccination and Functional Status-Findings from a State-Wide Online Screening Study.}, journal = {Vaccines}, volume = {11}, number = {3}, pages = {}, pmid = {36992274}, issn = {2076-393X}, support = {202120222023//Constructor University/ ; }, abstract = {(1) Background: Better understanding of post-/long-COVID and limitations in daily life due to the symptoms as well as the preventive potential of vaccinations is required. It is unclear whether the number of doses and timepoint interrelate with the trajectory of post-/long-COVID. Accordingly, we examined how many patients positively screened with post-/long-COVID were vaccinated and whether the vaccination status and the timepoint of vaccination in relation to the acute infection were related to post-/long-COVID symptom severity and patients' functional status (i.e., perceived symptom severity, social participation, workability, and life satisfaction) over time. (2) Methods: 235 patients suffering from post-/long-COVID were recruited into an online survey in Bavaria, Germany, and assessed at baseline (T1), after approximately three weeks (T2), and approximately four weeks (T3). (3) Results: 3.5% were not vaccinated, 2.3% were vaccinated once, 20% twice, and 53.3% three times. Overall, 20.9% did not indicate their vaccination status. The timepoint of vaccination was related to symptom severity at T1, and symptoms decreased significantly over time. Being vaccinated more often was associated with lower life satisfaction and workability at T2. (4) Conclusions: This study provides evidence to get vaccinated against SARS-CoV-2, as it has shown that symptom severity was lower in those patients who were vaccinated prior to the infection compared to those getting infected prior to or at the same time of the vaccination. However, the finding that being vaccinated against SARS-CoV-2 more often correlated with lower life satisfaction and workability requires more attention. There is still an urgent necessity for appropriate treatment for overcoming long-/post-COVID symptoms efficiently. Vaccination can be part of prevention measures, and there is still a need for a communication strategy providing objective information about the usefulness and risks of vaccinations.}, } @article {pmid36990807, year = {2023}, author = {Maher, M and Owens, L}, title = {SARS-CoV-2 infection and female reproductive health: A narrative review.}, journal = {Best practice & research. Clinical endocrinology & metabolism}, volume = {37}, number = {4}, pages = {101760}, pmid = {36990807}, issn = {1878-1594}, mesh = {Pregnancy ; Female ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Reproductive Health ; }, abstract = {The COVID-19 pandemic has had a profound global impact, affecting people's physical and mental health, and their social and economic circumstances. Mitigation measures have disproportionately affected women. Studies have reported menstrual cycle and psychological disturbance associated with the pandemic. Pregnancy is a risk factor for severe COVID-19 disease. Reports have also demonstrated associations between COVID-19 infection, vaccination and Long COVID syndrome and reproductive health disturbance. However, studies are limited and there may be significant geographical variation. Also there is bias amongst published studies, and menstrual cycle data was not included in COVID-19 and vaccine trials. Longitudinal population based studies are required. In this review we discuss existing data, along with recommendations for further research required in this area. We also discuss a pragmatic approach to women presenting with reproductive health disturbance in the era of the pandemic, encompassing a multi-system assessment of psychological, reproductive health and lifestyle.}, } @article {pmid36990762, year = {2023}, author = {O'Driscoll, DM and Young, AC}, title = {Contemporary Concise Review 2022: Sleep.}, journal = {Respirology (Carlton, Vic.)}, volume = {28}, number = {6}, pages = {518-524}, doi = {10.1111/resp.14500}, pmid = {36990762}, issn = {1440-1843}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/epidemiology/therapy ; Pandemics ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; Sleep ; *Sleep Apnea, Obstructive/complications/epidemiology/therapy ; }, abstract = {COVID-19 AND SLEEP: The COVID-19 pandemic is associated with an increase in insomnia and impaired sleep quality Health care workers are particularly susceptible and improved with cognitive behavioural therapy for insomnia (CBT-I) Long COVID has significant effects on sleep OSA impacts on the severity of acute COVID-19 illness OBSTRUCTIVE SLEEP APNOEA: Large trials of clinically representative patients confirm the cardiovascular benefits of CPAP treatment in OSA CPAP may improve long-term cognitive outcomes in OSA, but further research is needed Racial disparities in OSA prevalence and mortality risk are becoming evident Periodic evaluation of OSA risk in pregnancy is important as timing may be key for intervention to prevent or treat cardiovascular risk factors INSOMNIA: Comorbid insomnia and obstructive sleep apnoea (COMISA) can frequently co-exist and the combined negative effects of both may be deleterious, particularly to cardiovascular health There is evidence for effectiveness with novel orexin receptor antagonists.}, } @article {pmid36990297, year = {2023}, author = {Ceban, F and Kulzhabayeva, D and Rodrigues, NB and Di Vincenzo, JD and Gill, H and Subramaniapillai, M and Lui, LMW and Cao, B and Mansur, RB and Ho, RC and Burke, MJ and Rhee, TG and Rosenblat, JD and McIntyre, RS}, title = {COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis.}, journal = {Brain, behavior, and immunity}, volume = {111}, number = {}, pages = {211-229}, pmid = {36990297}, issn = {1090-2139}, mesh = {Humans ; *COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; SARS-CoV-2 ; Vaccination ; }, abstract = {Empirical evidence addressing the association between SARS-CoV-2 vaccination and long COVID would guide public health priorities and inform personal health decisions. Herein, the co-primary objectives are to determine the differential risk of long COVID in vaccinated versus unvaccinated patients, and the trajectory of long COVID following vaccination. Of 2775 articles identified via systematic search, 17 were included, and 6 were meta-analyzed. Meta-analytic results determined that at least one vaccine dose was associated with a protective effect against long COVID (OR 0.539, 95% CI 0.295-0.987, p = 0.045, N = 257 817). Qualitative analysis revealed that trajectories of pre-existing long COVID following vaccination were mixed, with most patients reporting no changes. The evidence herein supports SARS-CoV-2 vaccination for the prevention of long COVID, and recommends long COVID patients adhere to standard SARS-CoV-2 vaccination schedules.}, } @article {pmid36989909, year = {2023}, author = {Chow, CM and Schleyer, W and DeLisi, LE}, title = {The prevalence of psychiatric symptoms and their correlates as part of the long-COVID syndrome.}, journal = {Psychiatry research}, volume = {323}, number = {}, pages = {115166}, doi = {10.1016/j.psychres.2023.115166}, pmid = {36989909}, issn = {1872-7123}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Depression/epidemiology/psychology ; Retrospective Studies ; Prevalence ; Ethnicity ; SARS-CoV-2 ; Minority Groups ; }, abstract = {The Long COVID syndrome has now been documented clearly in the literature, but whether or not psychiatric symptoms are prominent is unclear. We performed a retrospective chart review of all patients receiving medical care during the pandemic in an outpatient Long-COVID specialty clinic that serves a large racial and ethnic minority population. As many as 44% of patients had symptoms that necessitated referrals to psychiatrists, predominantly depression or anxiety. Spanish speaking patients had greater COVID severity (48%) than did predominantly English speakers (15%). We conclude that the long COVID syndrome is predominantly a cluster of physical symptoms that are sequelae of the viral infection.}, } @article {pmid36989460, year = {2023}, author = {Ozery-Flato, M and Ein-Dor, L and Pinchasov, O and Dabush Kasa, M and Hexter, E and Chodick, G and Rosen-Zvi, M and Guindy, M}, title = {Impact of the COVID-19 Pandemic on Clinical Findings in Medical Imaging Exams in a Nationwide Israeli Health Organization: Observational Study.}, journal = {JMIR formative research}, volume = {7}, number = {}, pages = {e42930}, pmid = {36989460}, issn = {2561-326X}, abstract = {BACKGROUND: The outbreak of the COVID-19 pandemic had a major effect on the consumption of health care services. Changes in the use of routine diagnostic exams, increased incidences of postacute COVID-19 syndrome (PCS), and other pandemic-related factors may have influenced detected clinical conditions.

OBJECTIVE: This study aimed to analyze the impact of COVID-19 on the use of outpatient medical imaging services and clinical findings therein, specifically focusing on the time period after the launch of the Israeli COVID-19 vaccination campaign. In addition, the study tested whether the observed gains in abnormal findings may be linked to PCS or COVID-19 vaccination.

METHODS: Our data set included 572,480 ambulatory medical imaging patients in a national health organization from January 1, 2019, to August 31, 2021. We compared different measures of medical imaging utilization and clinical findings therein before and after the surge of the pandemic to identify significant changes. We also inspected the changes in the rate of abnormal findings during the pandemic after adjusting for changes in medical imaging utilization. Finally, for imaging classes that showed increased rates of abnormal findings, we measured the causal associations between SARS-CoV-2 infection, COVID-19-related hospitalization (indicative of COVID-19 complications), and COVID-19 vaccination and future risk for abnormal findings. To adjust for a multitude of confounding factors, we used causal inference methodologies.

RESULTS: After the initial drop in the utilization of routine medical imaging due to the first COVID-19 wave, the number of these exams has increased but with lower proportions of older patients, patients with comorbidities, women, and vaccine-hesitant patients. Furthermore, we observed significant gains in the rate of abnormal findings, specifically in musculoskeletal magnetic resonance (MR-MSK) and brain computed tomography (CT-brain) exams. These results also persisted after adjusting for the changes in medical imaging utilization. Demonstrated causal associations included the following: SARS-CoV-2 infection increasing the risk for an abnormal finding in a CT-brain exam (odds ratio [OR] 1.4, 95% CI 1.1-1.7) and COVID-19-related hospitalization increasing the risk for abnormal findings in an MR-MSK exam (OR 3.1, 95% CI 1.9-5.3).

CONCLUSIONS: COVID-19 impacted the use of ambulatory imaging exams, with greater avoidance among patients at higher risk for COVID-19 complications: older patients, patients with comorbidities, and nonvaccinated patients. Causal analysis results imply that PCS may have contributed to the observed gains in abnormal findings in MR-MSK and CT-brain exams.}, } @article {pmid36987520, year = {2023}, author = {Alvergne, A and Kountourides, G and Argentieri, MA and Agyen, L and Rogers, N and Knight, D and Sharp, GC and Maybin, JA and Olszewska, Z}, title = {A retrospective case-control study on menstrual cycle changes following COVID-19 vaccination and disease.}, journal = {iScience}, volume = {26}, number = {4}, pages = {106401}, pmid = {36987520}, issn = {2589-0042}, support = {209589/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; G1002033/MRC_/Medical Research Council/United Kingdom ; MR/N022556/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {There has been increasing public concern that COVID-19 vaccination causes menstrual disturbance regarding the relative effect of vaccination compared to SARS-CoV-2 infection. Our objectives were to test potential risk factors for reporting menstrual cycle changes following COVID-19 vaccination and to compare menstrual parameters following COVID-19 vaccination and COVID-19 disease. We performed a secondary analysis of a retrospective online survey conducted in the UK in March 2021. In pre-menopausal vaccinated participants (n = 4,989), 18% reported menstrual cycle changes after their first COVID-19 vaccine injection. The prevalence of reporting any menstrual changes was higher for women who smoke, have a history of COVID-19 disease, or are not using estradiol-containing contraceptives. In a second sample including both vaccinated and unvaccinated participants (n = 12,579), COVID-19 vaccination alone was not associated with abnormal menstrual cycle parameters, while a history of COVID-19 disease was associated with an increased risk of reporting heavier bleeding, "missed" periods, and inter-menstrual bleeding.}, } @article {pmid36987476, year = {2023}, author = {Bankole, AA and Nwaonu, J and Saeed, J}, title = {Impact of SARS-CoV-2/COVID-19 on Provision of Medical Care to Patients With Systemic Autoimmune Rheumatic Disease and the Practice of Rheumatology.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35402}, pmid = {36987476}, issn = {2168-8184}, abstract = {The SARS-CoV-2 pandemic has had a significant impact on the healthcare field that resulted in changes to the way safe and effective medical care is delivered. The effects range from service disruption including ambulatory clinic closure due to both patient and provider concerns, to lack of capacity in hospital services. In rheumatology, there were other effects including viral infection-related autoantibody production, concerns about the use of systemic immunosuppression in the presence of an infectious pandemic and even concerns for viral infection-induced flares of rheumatic disease. Coronavirus disease 2019 (COVID-19) led to the rapid adoption of innovative technologies that permitted the introduction and increased use of telemedicine via a number of platforms. Rapid discoveries and innovations led to the development of diagnostic and therapeutic agents in the management of COVID-19. Scientific advancement and discoveries around COVID-19 infection, symptoms, autoantibody production, chronic sequela and the repurposing of rheumatic immunosuppressive agents led to improved survival and an expanded role for the rheumatologist. Rheumatologists may sometimes be involved in the diagnosis and management of the hospitalized COVID-19 patient. In the ambulatory clinic, a rheumatologist also helps to differentiate between symptoms of long COVID and those of systemic autoimmune rheumatic disease (SARD). Rheumatologists must also grapple with the concerns related to immunosuppressive therapy and the risk of COVID-19 infections. In addition, there are concerns around vaccine effectiveness in people with SARD and those on immunosuppressive medications. Although the SARS-CoV-2 pandemic and the effects on healthcare resulted in difficulties, both patients and providers have risen to the challenge. The long-term outcome of COVID-19 for the medical system and rheumatologists in particular is not yet fully understood and will need further study. This review concentrates on the changing role of the rheumatologists, improved understanding of rheumatic disease and immunosuppressive therapies in the wake of the pandemic and how this has led to an improvement in the care of patients with COVID-19.}, } @article {pmid36985286, year = {2023}, author = {Amiama-Roig, A and Pérez-Martínez, L and Rodríguez Ledo, P and Verdugo-Sivianes, EM and Blanco, JR}, title = {Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?.}, journal = {Microorganisms}, volume = {11}, number = {3}, pages = {}, pmid = {36985286}, issn = {2076-2607}, abstract = {The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.}, } @article {pmid36983936, year = {2023}, author = {Vasichkina, E and Kofeynikova, O and Fetisova, S and Starshinova, AY and Sheyanova, E and Vershinina, T and Ryzhkov, A and Skripnik, A and Alekseeva, D and Nechaeva, E and Glushkova, A and Kudlay, D and Pervunina, T and Starshinova, A}, title = {Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {36983936}, issn = {2075-1729}, support = {075-15-2022-301//Federal Almazov North-West Medical Research Centre/ ; }, abstract = {The question of COVID-19 and long-COVID-19 course in children remains unsolved. This infection in children, which is associated with COVID-19, can vary from asymptomatic to systemic damage of various systems. Multisystem inflammatory syndrome in children, associated with SARS-CoV-2 (MIS-C), is a serious condition in children and adolescents after experiencing COVID-19. Published data on MIS-C have indicated that the inflammation can be registered in the gastrointestinal tract (60-100%), as well as in cardiovascular (80%), nervous (29-58%), and respiratory (21-65%) systems. However, with the changing characteristics of SARS-CoV-2, the manifestations of COVID-19 and long-COVID-19 in children have also been changing. Currently, there is no clear understanding of the development of severe COVID-19 and MIS-C in children, especially after being exposed to patients with COVID-19. We presented two new clinical courses of multisystem inflammatory syndrome in children with severe multisystem damage after close contact to relatives with COVID-19 or long-COVID-19. Thus, high-risk children, who are positive for SARS-CoV-2 infection after contact with COVID-19 patients, should be clinically managed during the first few months. The identification of the disease complexity requires the involvement of neurologists, cardiologists, and other specialists.}, } @article {pmid36983838, year = {2023}, author = {Sova, M and Sovova, E and Ozana, J and Moravcova, K and Sovova, M and Jelinek, L and Mizera, J and Genzor, S}, title = {Post-COVID Syndrome and Cardiorespiratory Fitness-26-Month Experience of Single Center.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {36983838}, issn = {2075-1729}, abstract = {INTRODUCTION: Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity that involves persistent physical, medical, and cognitive sequelae following COVID-19. Decreased fitness has repeatedly been reported in numerous studies dealing with post-COVID syndrome, however, it is still not fully clear which groups of patients may be more susceptible for persisting symptoms.

AIM: The aim of our study was to evaluate the number of post-COVID patients with cardiac symptoms, where these patients were evaluated by CPET and the results compared with a control group of patients.

METHODS: Follow-up of patients in post-COVID outpatient clinic from 1 March 2020 to 31 May 2022. Inclusion criteria were positive PCR test for SARS-CoV-2 and age 18-100. The initial examination was performed 4-12 weeks after the disease onset. All patients with possible cardiac symptoms had completed cardiopulmonary exercise testing. The control group was randomly selected from a database of clients in 2019, with the preventive reason for evaluation.

RESULTS: From 1 March 2020 to 31 May 2022, 2732 patients (45.7% males) were evaluated with a mean age of 54.6 ± 14.7. CPET was indicated only in 97 patients (3.5%). Seventy-four patients (26 male) achieved the exercise maximum and a comparison were made with a control group (same age (p = 0.801), BMI (p = 0.721), and sex ratio). No significant dependence between the parameter VO2 max mL/kg/min and post-COVID disability was demonstrated (p = 0.412). Spearman's correlation analysis did not show a significant relationship between the parameter VO2 max mL/kg/min and the severity of COVID-19 (p = 0.285).

CONCLUSIONS: Cardiac symptoms occurred in only a small percentage of patients in our study. There is a need for further studies that would objectively evaluate the effect of COVID-19 disease on the patient's health.}, } @article {pmid36983234, year = {2023}, author = {Gounaridi, MI and Vontetsianos, A and Oikonomou, E and Theofilis, P and Chynkiamis, N and Lampsas, S and Anastasiou, A and Papamikroulis, GA and Katsianos, E and Kalogeras, K and Pesiridis, T and Tsatsaragkou, A and Vavuranakis, M and Koulouris, N and Siasos, G}, title = {The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {6}, pages = {}, pmid = {36983234}, issn = {2077-0383}, abstract = {Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.}, } @article {pmid36983124, year = {2023}, author = {Podrug, M and Koren, P and Dražić Maras, E and Podrug, J and Čulić, V and Perissiou, M and Bruno, RM and Mudnić, I and Boban, M and Jerončić, A}, title = {Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {6}, pages = {}, pmid = {36983124}, issn = {2077-0383}, support = {No. IP-2018-01-4729//Croatian Science Foundation/ ; }, abstract = {COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2-3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics-cfPWV, AIx@HR75, and cDBP as well as DBP and MAP-responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2-3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.}, } @article {pmid36982693, year = {2023}, author = {Mancini, M and Natoli, S and Gardoni, F and Di Luca, M and Pisani, A}, title = {Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982693}, issn = {1422-0067}, support = {ID 3433068//Fondazione Regionale per la Ricerca Biomedica, Regione Lombardia/ ; }, mesh = {Humans ; Dopamine/metabolism ; Neuroinflammatory Diseases ; *COVID-19 ; SARS-CoV-2/metabolism ; *Parkinson Disease/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson's disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.}, } @article {pmid36982589, year = {2023}, author = {Ranucci, M and Baryshnikova, E and Anguissola, M and Pugliese, S and Falco, M and Menicanti, L}, title = {The Long Term Residual Effects of COVID-Associated Coagulopathy.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982589}, issn = {1422-0067}, support = {N/A//Italian Ministry of Health/ ; }, mesh = {Humans ; *COVID-19/complications ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; *Blood Coagulation Disorders ; Blood Coagulation ; *Thrombosis ; }, abstract = {During the acute phase of COVID-19, many patients experience a complex coagulopathy characterized by a procoagulant pattern. The present study investigates the persistence of hemostatic changes in post-COVID patients at a long-term follow up, and the link with the persistence of physical and neuropsychological symptoms. We completed a prospective cohort study on 102 post-COVID patients. Standard coagulation and viscoelastic tests were performed, along with an assessment of persistent symptoms and recording of acute phase details. A procoagulant state was adjudicated in the presence of fibrinogen > 400 mg/dL, or D-dimer > 500 ng/mL, or platelet count > 450,000 cells/µL, or a maxim clot lysis at viscoelastic test < 2%. A procoagulant state was identified in 75% of the patients at 3 months follow up, 50% at 6 months, and 30% at 12-18 months. Factors associated with the persistence of a procoagulant state were age, severity of the acute phase, and persistence of symptoms. Patients with major physical symptoms carry a procoagulant state relative risk of 2.8 (95% confidence interval 1.17-6.7, p = 0.019). The association between persistent symptoms and a procoagulant state raises the hypothesis that an ongoing process of thrombi formation and/or persistent microthrombosis may be responsible for the main physical symptoms in long-COVID patients.}, } @article {pmid36982194, year = {2023}, author = {Tate, WP and Walker, MOM and Peppercorn, K and Blair, ALH and Edgar, CD}, title = {Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982194}, issn = {1422-0067}, support = {no grant number//ANZMES -NZA ME/CFS natiuonal disease advisory association/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology/therapy/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Causality ; }, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.}, } @article {pmid36982151, year = {2023}, author = {Calvani, R and Gervasoni, J and Picca, A and Ciciarello, F and Galluzzo, V and Coelho-Júnior, HJ and Di Mario, C and Gremese, E and Lomuscio, S and Paglionico, AM and Santucci, L and Tolusso, B and Urbani, A and Marini, F and Marzetti, E and Landi, F and Tosato, M and , }, title = {Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982151}, issn = {1422-0067}, mesh = {Humans ; Adult ; *Post-Acute COVID-19 Syndrome ; Ascorbic Acid/therapeutic use ; Citrulline/metabolism ; *COVID-19 ; SARS-CoV-2/metabolism ; Arginine/metabolism ; Nitric Oxide/metabolism ; Ornithine ; Dietary Supplements ; }, abstract = {Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.}, } @article {pmid36981968, year = {2023}, author = {Avittan, H and Kustovs, D}, title = {Cognition and Mental Health in Pediatric Patients Following COVID-19.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {6}, pages = {}, pmid = {36981968}, issn = {1660-4601}, mesh = {Humans ; Child ; *COVID-19/epidemiology ; Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Anxiety/epidemiology/psychology ; Cognition ; }, abstract = {The global coronavirus pandemic has significantly impacted public health and has been a research subject since its emergence in 2019. The acute phase of the disease leads to pulmonary and non-pulmonary manifestations, which in some individuals may progress to long-lasting symptoms. In this article, we conducted a narrative review of the current literature to summarize current knowledge regarding long COVID syndrome in children, focusing on cognitive symptoms. The review included a search of three databases (PubMed, Embase, and Web of Science) using the key phrases "post COVID-19 cognitive pediatric", "long COVID pediatric", "mental health long COVID children", and "COVID-19 cognitive symptoms". A total of 102 studies were included. The review revealed that the main long-term cognitive symptoms following COVID-19 were memory and concentration deficits, sleep disturbances, and psychiatric states such as anxiety and stress. In addition to the direct physiological effects of a viral infection, there are psychological, behavioral, and social factors contributing to cognitive impairment, which should be addressed regarding the pediatric population. The high prevalence of neurocognitive symptoms in children following COVID-19 emphasizes the importance of understanding the mechanisms of nervous system involvement.}, } @article {pmid36981826, year = {2023}, author = {Panagiotides, NG and Zimprich, F and Machold, K and Schlager, O and Müller, M and Ertl, S and Löffler-Stastka, H and Koppensteiner, R and Wadowski, PP}, title = {A Case of Autoimmune Small Fiber Neuropathy as Possible Post COVID Sequelae.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {6}, pages = {}, pmid = {36981826}, issn = {1660-4601}, mesh = {Humans ; Female ; *COVID-19/complications ; SARS-CoV-2 ; Paresthesia ; *Small Fiber Neuropathy/etiology/complications ; Headache/complications ; Arthralgia ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is reported to induce and augment autoimmune processes. Moreover, postinfectious effects of coronavirus disease 2019 (COVID-19) are still poorly understood and often resemble symptoms of the acute infection phase. A patient with swollen extremities was presented to the Department of Angiology at the Medical University of Vienna with complaints of muscle and joint pain, paresthesia, and arterial hypertension with intense headache. Prior to these complaints, she had been suffering from various symptoms since November 2020, following a SARS-CoV-2 infection in the same month. These included recurrent sore throat, heartburn, dizziness, and headache. Paresthesia and muscle and joint pain started in temporal relation to a human papillomavirus (HPV) vaccination. Since the patient was suffering from severe pain, intensive pain management was performed. Skin and nerve biopsies revealed autoimmune small fiber neuropathy. The patient's condition could be related to COVID-19, as her first symptoms began in temporal relation to the SARS-CoV-2 infection. Furthermore, in the disease course, antinuclear (ANA) and anti-Ro antibodies, as well as anti-cyclic citrullinated peptide (anti-CCP) antibodies, could be detected. Together with the symptoms of xerophthalmia and pharyngeal dryness, primary Sjögren's syndrome was diagnosed. In conclusion, though biopsy results could not distinguish a cause of the disease, SARS-CoV-2 infection can be discussed as a likely trigger for the patient's autoimmune reactions.}, } @article {pmid36981522, year = {2023}, author = {Petracek, LS and Broussard, CA and Swope, RL and Rowe, PC}, title = {A Case Study of Successful Application of the Principles of ME/CFS Care to an Individual with Long COVID.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {36981522}, issn = {2227-9032}, abstract = {Persistent fatigue is one of the most common symptoms of post-COVID conditions, also termed long COVID. At the extreme end of the severity spectrum, some individuals with long COVID also meet the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), raising the possibility that symptom management approaches for ME/CFS may benefit some long COVID patients. We describe the long-term outcomes of a 19-year-old male who developed profound impairment consistent with ME/CFS after a SARS-CoV-2 infection early in the pandemic. We evaluated and treated him using our clinic's approach to ME/CFS. This included a history and physical examination that ascertained joint hypermobility, pathological reflexes, physical therapy maneuvers to look for a range of motion restrictions in the limbs and spine, orthostatic testing, and screening laboratory studies. He was found to have profound postural tachycardia syndrome, several ranges of motion restrictions, and mast cell activation syndrome. He was treated according to our clinic's guidelines for managing ME/CFS, which included manual physical therapy maneuvers and both non-pharmacologic measures and medications directed at postural tachycardia syndrome and mast cell activation. He experienced significant improvement in his symptoms over 30 months. His case emphasizes how the application of the principles of treating ME/CFS has the potential to provide a direction for treating long COVID.}, } @article {pmid36980424, year = {2023}, author = {D'Aloisio, R and Ruggeri, ML and D'Onofrio, G and Formenti, F and Gironi, M and Di Nicola, M and Porreca, A and Toto, L and Mastropasqua, R}, title = {Choroidal and Retinal Vascular Findings in Patients with COVID-19 Complicated with Pneumonia: Widefield Imaging.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {6}, pages = {}, pmid = {36980424}, issn = {2075-4418}, abstract = {PURPOSE: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge.

METHODS: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed.

RESULTS: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found.

CONCLUSION: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye.}, } @article {pmid36980155, year = {2023}, author = {Mariani, F and Morello, R and Traini, DO and La Rocca, A and De Rose, C and Valentini, P and Buonsenso, D}, title = {Risk Factors for Persistent Anosmia and Dysgeusia in Children with SARS-CoV-2 Infection: A Retrospective Study.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {3}, pages = {}, pmid = {36980155}, issn = {2227-9067}, support = {65925795//Pfizer (Italy)/ ; }, abstract = {BACKGROUND: Olfactory and gustative dysfunctions are two of the most common post-acute sequelae of SARS-CoV-2 infection in children, which can have a negative impact on the routines of children and families. As several children have had COVID-19 since the Omicron variant, it is important to investigate if this increase in infections is reflected in higher olfactory/taste disfunctions. The primary aim of this study was to characterize the presence of olfactory/gustative problems in a cohort of children, its evolution, and its association with risk factors such as COVID-19 variant, hospitalization, presence of olfactory/gustative dysfunction during the acute phase, and vaccination.

METHODS: This was a retrospective analysis of children with microbiologically confirmed SARS-CoV-2 infection evaluated in person at a referral pediatric post-COVID-19 clinic in Rome, Italy. We included children younger than 19 years old, evaluated from the beginning of the pandemic up to October 2022. At specific timepoints, we investigated the presence of olfactory/taste disfunctions and evaluated them according to the SARS-CoV-2 variants circulating at the time of infection.

RESULTS: A total of 1250 children (650 females; 52.0%) with a mean age of 6.77 (±4.12) years were included in the study. At 3, 6, 12, and 18 months, 12 (9.6%), 7 (5.6%), 2 (1.6%), and 1 (0.8%) of the children reported anosmia and dysgeusia post-COVID-19 infection, respectively. The presence of anosmia and dysgeusia during the acute phase of infection and being infected with a pre-Omicron variant were found to be significant risk factors for persistent olfactory and gustatory dysfunction during all follow-up periods.

CONCLUSIONS: anosmia and dysgeusia symptoms tended to decrease gradually over time, but not all children recovered quickly.}, } @article {pmid36979253, year = {2023}, author = {Torales, J and González-Urbieta, I and Barrios, I and Waisman-Campos, M and Terrazas-Landivar, A and Viola, L and Caycho-Rodríguez, T and Melgarejo, O and Navarro, R and García, O and Almirón-Santacruz, J and Castaldelli-Maia, JM and Ventriglio, A}, title = {"Pandemic Fatigue" in South America: A Multi-Center Report from Argentina, Bolivia, Paraguay, Peru, and Uruguay.}, journal = {Brain sciences}, volume = {13}, number = {3}, pages = {}, pmid = {36979253}, issn = {2076-3425}, abstract = {The COVID-19 pandemic has had a heavy impact on daily life, leading to physical and psychosocial consequences. Nowadays, clinicians and health researchers are particularly interested in describing and facing the long-term effects of COVID-19, also known as "long-COVID syndrome". Pandemic fatigue has been defined as a cluster of demotivation, tiredness, and psychological effects that emerge gradually over time after the infection or through the adoption of the recommended measures to combat it. In this study, we report the findings of a large survey conducted in South America involving 1448 participants (mean age: 33.9 ± 11.2 years old) from Argentina, Bolivia, Uruguay, Peru, and Paraguay. An online survey was launched through the common social media based on a specific assessment aimed to detect the prevalence of pandemic fatigue and associated factors. Socio-demographic characteristics, medical, and personal information were collected; the Pandemic Fatigue Scale (PFS) and the Coronavirus Anxiety Scale (CAS) were also administered. We found mid-levels of pandemic fatigue among respondents (21.7 ± 7.95 score at PFS) as well as significant anxiety related to the COVID-19 pandemic (1.56 ± 2.76 score at CAS). In addition, pandemic fatigue was significantly associated with the experience of the loss of a relative/friend due to COVID-19, anxiety related to the infection, and reliance on social media as a primary source of information on the pandemic. Vaccination significantly reduced the levels of fatigue among respondents. Our findings may add to the international debate regarding the long-term health consequences of the COVID-19 pandemic and strategies to manage them in the general population of South America.}, } @article {pmid36979062, year = {2023}, author = {Tudoran, C and Bende, R and Bende, F and Giurgi-Oncu, C and Enache, A and Dumache, R and Tudoran, M}, title = {Connections between Diabetes Mellitus and Metabolic Syndrome and the Outcome of Cardiac Dysfunctions Diagnosed during the Recovery from COVID-19 in Patients without a Previous History of Cardiovascular Diseases.}, journal = {Biology}, volume = {12}, number = {3}, pages = {}, pmid = {36979062}, issn = {2079-7737}, abstract = {(1) Background: Throughout the COVID-19 pandemic, it became obvious that individuals suffering with obesity, diabetes mellitus (T2DM), and metabolic syndrome (MS) frequently developed persisting cardiovascular complications, which were partially able to explain the onset of the long-COVID-19 syndrome. (2) Methods: Our aim was to document, by transthoracic echocardiography (TTE), the presence of cardiac alterations in 112 patients suffering from post-acute COVID-19 syndrome and T2DM, MS, and/or obesity, in comparison to 91 individuals without metabolic dysfunctions (MD); (3) Results: in patients with MD, TTE borderline/abnormal left (LVF) and/or right ventricular function (RVF), alongside diastolic dysfunction (DD), were more frequently evidenced, when compared to controls (p ˂ 0.001). Statistically significant associations between TTE parameters and the number of factors defining MS, the triglyceride-glucose (TyG) index, the severity of the SARS-CoV-2 infection, and the number of persisting symptoms (p ˂ 0.001) were noted. Significant predictive values for the initial C-reactive protein and TyG index levels, both for the initial and the 6-month follow-up levels of these TTE abnormalities (p ˂ 0.001), were highlighted by means of a multivariate regression analysis. (4) Conclusions: in diabetic patients with MS and/or obesity with comorbid post-acute COVID-19 syndrome, a comprehensive TTE delineates various cardiovascular alterations, when compared with controls. After 6 months, LVF and RVF appeared to normalize, however, the DD-although somewhat improved-did persist in approximately a quarter of patients with MD, possibly due to chronic myocardial changes.}, } @article {pmid36978767, year = {2023}, author = {Invitto, S and Boscolo-Rizzo, P and Fantin, F and Bonifati, DM and de Filippis, C and Emanuelli, E and Frezza, D and Giopato, F and Caggiula, M and Schito, A and Ciccarese, V and Spinato, G}, title = {Exploratory Study on Chemosensory Event-Related Potentials in Long COVID-19 and Mild Cognitive Impairment: A Common Pathway?.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {10}, number = {3}, pages = {}, pmid = {36978767}, issn = {2306-5354}, support = {RIPARTI - Procedure Number: A9 Project Code: 77e95c8d//Regione Puglia/ ; }, abstract = {People affected by the Long COVID-19 (LC) syndrome often show clinical manifestations that are similar to those observed in patients with mild cognitive impairments (MCI), such as olfactory dysfunction (OD), brain fog, and cognitive and attentional diseases. This study aimed to investigate the chemosensory-evoked related potentials (CSERP) in LC and MCI to understand if there is a common pathway for the similarity of symptoms associated with these disorders. Eighteen LC patients (mean age 53; s.d. = 7), 12 patients diagnosed with MCI (mean age 67; s.d. = 6), and 10 healthy control subjects (mean age 66; s.d. = 5, 7) were recruited for this exploratory study. All of them performed a chemosensory event-related potentials (CSERP) task with the administration of trigeminal stimulations (e.g., the odorants cinnamaldehyde and eucalyptus). Study results highlighted that MCI and LC showed reduced N1 amplitude, particularly in the left frontoparietal network, involved in working memory and attentional deficits, and a reduction of P3 latency in LC. This study lays the foundations for evaluating aspects of LC as a process that could trigger long-term functional alterations, and CSERPs could be considered valid biomarkers for assessing the progress of OD and an indicator of other impairments (e.g., attentional and cognitive impairments), as they occur in MCI.}, } @article {pmid36978360, year = {2023}, author = {Cameron, DJ and McWhinney, SR}, title = {Consequences of Contracting COVID-19 or Taking the COVID-19 Vaccine for Individuals with a History of Lyme Disease.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36978360}, issn = {2079-6382}, abstract = {Individuals with Lyme disease can be very symptomatic. This survey compares the burden of illness for individuals with a history of Lyme disease (HLD) with individuals with a HLD who have either contracted COVID-19 or who have taken the COVID-19 vaccine. The findings describe the relative symptom burden among these three groups using a cross-sectional descriptive survey investigating the burden of Lyme disease in a pandemic. The survey includes the General Symptom Questionnaire-30 (GSQ-30), a brief self-report scale designed to assess the symptom burden in Lyme disease (LD). The results of this survey show that the overall burden of illness among individuals with HLD is not significantly different after contracting COVID-19 or after COVID-19 vaccination. A new survey will be needed to better understand why one in five individuals with a HLD reported long COVID after contracting COVID-19. These results should help clinicians and their patients to discuss the consequences of contracting a COVID-19 infection or being vaccinated against COVID-19.}, } @article {pmid36977809, year = {2023}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Anders, M and Raboch, J and Ptacek, R and Kream, RM}, title = {Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {6}, pages = {2621-2626}, pmid = {36977809}, issn = {1573-6830}, mesh = {Humans ; Animals ; *Prions/metabolism ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species ; *COVID-19 ; SARS-CoV-2 ; Mammals/metabolism ; }, abstract = {Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.}, } @article {pmid36977491, year = {2023}, author = {Bandara, T and Deshmukh, HA and Abdalla, M and Sathyapalan, T}, title = {Metabolic and Endocrine Complications of Long-COVID-19: A Review.}, journal = {Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association}, volume = {131}, number = {6}, pages = {367-374}, doi = {10.1055/a-2063-8697}, pmid = {36977491}, issn = {1439-3646}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Endocrine System ; }, abstract = {Over the past two years, the outbreak of coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has centralized the interest of the health care systems and the scientific world. The majority of COVID-19-infected individuals recover fully. However, about 12-50% of patients experience various mid- and long-term effects after recovering from the initial illness. These mid- and long-term effects are collectively known as post-COVID-19 condition or 'long-COVID'. In the coming months, the long-term consequences of COVID-19 on the metabolic and endocrine systems may expect to rise and pose a global healthcare challenge. This review article discusses the possible metabolic and endocrine complications of long-COVID and the relevant research findings.}, } @article {pmid36976797, year = {2023}, author = {Sandle, GI and Herod, MR and Fontana, J and Lippiat, JD and Stockley, PG}, title = {Is intestinal transport dysfunctional in COVID-19-related diarrhea?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {324}, number = {5}, pages = {G415-G418}, pmid = {36976797}, issn = {1522-1547}, support = {MR/S007229/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Epithelial Sodium Channels/metabolism ; Post-Acute COVID-19 Syndrome ; Diarrhea ; }, abstract = {Diarrhea, often severe, is a recognized and frequently early symptom during acute COVID-19 infection and may persist or develop for the first time in patients with long-COVID, with socioeconomic consequences. Diarrheal mechanisms in these cases are poorly understood. There is evidence for disruption of intestinal epithelial barrier function and also for changes in the gut microbiome, which is critical for gut immunity and metabolism. Whether the SARS-CoV-2 virus has adverse effects on intestinal transport proteins is unclear. However, the ability of the virus to inhibit expression and activity of an aldosterone-regulated epithelial sodium (Na[+]) channel (ENaC) present in human distal colon, which is responsible for Na[+] and water salvage, points to possible disruption of other intestinal transport proteins during COVID-19 infection. In this Perspective, we develop this idea by highlighting possible intestinal transport protein targets for the SARS-CoV-2 virus and discussing how their interactions might be explored in the laboratory.}, } @article {pmid36976485, year = {2023}, author = {Szabo, S and Gyires, K and Zayachkivska, O}, title = {Introduction to the 'long COVID' special issue.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {549}, doi = {10.1007/s10787-023-01197-x}, pmid = {36976485}, issn = {1568-5608}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; }, } @article {pmid36974333, year = {2023}, author = {Onyeaghala, AA and Anyiam, AF and Husaini, DC and Onyeaghala, EO and Obi, E}, title = {Herbal supplements as treatment options for COVID-19: A call for clinical development of herbal supplements for emerging and re-emerging viral threats in Sub-Saharan Africa.}, journal = {Scientific African}, volume = {20}, number = {}, pages = {e01627}, pmid = {36974333}, issn = {2468-2276}, abstract = {The advent of Corona virus Disease 2019 (COVID-19) distorted health systems of many countries. Efforts have been made to either develop new treatment solutions such as vaccines or repurpose previously adopted drugs. Challenges in accessing available treatment, inadequate, non-existent, or overstretched healthcare facilities, long COVID disease, cultural practices and beliefs about vaccination, vaccine hesitancy, availability, accessibility and perceived safety of herbal supplements seem to be major factors propelling individuals to use herbal supplements. Published reports advocating for clinical development of herbal supplements for COVID-19 and other emerging and re-emerging viral diseases are sparse. This paper aims to review the pathogenesis of COVID-19, use of herbal products during the pandemic and make case for clinical development of herbal supplements through the adoption of modern and acceptable technologies and research processes. This was a scoping review. Database searches of Google Scholar, PubMed and ResearchGate among others were performed using related keywords to identify relevant journals and lists of primary articles. Clinical trial databases:-Clinicaltrial.gov, Pan African Clinical Trial Registry (PACTR) and WHO international clinical trial registry (ICTRP) were reviewed to extract data. The use of herbal supplements during COVID-19 was not only peculiar to individuals living in Sub-Saharan Africa, but a global practice. Herbal supplements recommended to manage COVID-19 have not been validated using clinical trials. Available data showed that the number of herbal supplements undergoing clinical trial for COVID-19 indication in Africa was low. The availability of medicinal plants in Sub-Saharan Africa if well explored has great potentials to address various emerging and re-emerging viral diseases confronting the region. The economic potential of clinically validated herbal supplements are huge, and tapping into this opportunity created by preference of population to herbal supplement could increase export of herbal supplement and gross domestic product (GDP) of respective countries in Africa.}, } @article {pmid36972892, year = {2023}, author = {Wang, S and Farland, LV and Gaskins, AJ and Mortazavi, J and Wang, YX and Tamimi, RM and Rich-Edwards, JW and Zhang, D and Terry, KL and Chavarro, JE and Missmer, SA}, title = {Association of laparoscopically-confirmed endometriosis with long COVID-19: a prospective cohort study.}, journal = {American journal of obstetrics and gynecology}, volume = {228}, number = {6}, pages = {714.e1-714.e13}, pmid = {36972892}, issn = {1097-6868}, support = {U01 HL145386/HL/NHLBI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; R01 HD096033/HD/NICHD NIH HHS/United States ; R24 ES028521/ES/NIEHS NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; *COVID-19 ; *Endometriosis/diagnosis ; *Infertility ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19.

OBJECTIVE: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19.

STUDY DESIGN: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases).

RESULTS: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis.

CONCLUSION: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.}, } @article {pmid36972723, year = {2023}, author = {Morgan, J}, title = {Long COVID? What is that?.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {6}, pages = {515-517}, doi = {10.1016/S2213-2600(23)00126-1}, pmid = {36972723}, issn = {2213-2619}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36969629, year = {2023}, author = {Schmachtenberg, T and Müller, F and Kranz, J and Dragaqina, A and Wegener, G and Königs, G and Roder, S}, title = {How do long COVID patients perceive their current life situation and occupational perspective? Results of a qualitative interview study in Germany.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1155193}, pmid = {36969629}, issn = {2296-2565}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19 ; Qualitative Research ; Germany/epidemiology ; }, abstract = {INTRODUCTION: Many people experience persistent or new-onset symptoms such as fatigue or cognitive problems after an acute infection with COVID-19. This phenomenon, known as long COVID, impacts physical and mental wellbeing, and may affect perceived quality of life and occupational perspectives likewise. The aim of this study is to gain a deeper understanding of how people with long COVID experience health-related restrictions in their daily life and their occupational situation, and to identify key challenges they face.

METHODS: Guided qualitative interviews were conducted with 25 people with long COVID. The interviews were transcribed according to Dresing/Pehl and Kuckartz and analyzed using qualitative content analysis. Afterward, a systematic comparison of the data and a reflection under consideration of lifeworld-theoretical approaches (Berger and Luckmann) were carried out.

RESULTS: The interviews revealed that many participants have severe symptoms which strongly impair them in perform daily and work-related activities, and in their personal interests. Many interviewees already reach their stress limit during routine household activities or childcare. Of the 25 participants, 19 experienced limitations in pursuing leisure activities, and 10 of the 23 interviewees with jobs reported being on sick leave for several months. Several respondents who had vocational reintegration are still affected by ongoing symptoms that affect their work performance considerably. This leads to uncertainty, role conflicts, a decline in social contacts, and decreased incomes, which contribute to an impairment in their quality of life.

CONCLUSIONS: This study shows the huge need for specific support for people with long COVID in different areas of life. To prevent people with long COVID from finding themselves in social and economic precarity, decision-makers should develop strategies to systematically support them in their sustainable reintegration into the workforce. The focus should be on creating long COVID-sensitive workplaces, compensating for decreased incomes, and improving access to relief services such as vocational reintegration. We argue, that a shift of perspectives is necessary and that long COVID should be considered rather as a "social disease" with considerably impairments in the social life of those affected.

TRIAL REGISTRATION: The study is registered in the German register for clinical trials (DRKS00026007).}, } @article {pmid36969243, year = {2023}, author = {Ancona, G and Alagna, L and Alteri, C and Palomba, E and Tonizzo, A and Pastena, A and Muscatello, A and Gori, A and Bandera, A}, title = {Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1080043}, pmid = {36969243}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; }, abstract = {The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.}, } @article {pmid36969241, year = {2023}, author = {Bonilla, H and Peluso, MJ and Rodgers, K and Aberg, JA and Patterson, TF and Tamburro, R and Baizer, L and Goldman, JD and Rouphael, N and Deitchman, A and Fine, J and Fontelo, P and Kim, AY and Shaw, G and Stratford, J and Ceger, P and Costantine, MM and Fisher, L and O'Brien, L and Maughan, C and Quigley, JG and Gabbay, V and Mohandas, S and Williams, D and McComsey, GA}, title = {Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1129459}, pmid = {36969241}, issn = {1664-3224}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {United States ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Motivation ; }, abstract = {Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.}, } @article {pmid36969239, year = {2023}, author = {Carter, B and Huang, P and Liu, G and Liang, Y and Lin, PJC and Peng, BH and McKay, LGA and Dimitrakakis, A and Hsu, J and Tat, V and Saenkham-Huntsinger, P and Chen, J and Kaseke, C and Gaiha, GD and Xu, Q and Griffiths, A and Tam, YK and Tseng, CK and Gifford, DK}, title = {A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1135815}, pmid = {36969239}, issn = {1664-3224}, mesh = {Mice ; Animals ; Humans ; Mice, Transgenic ; *SARS-CoV-2 ; CD8-Positive T-Lymphocytes ; COVID-19 Vaccines ; *COVID-19/prevention & control ; Post-Acute COVID-19 Syndrome ; Antibodies, Neutralizing ; Epitopes ; RNA, Messenger ; }, abstract = {Licensed COVID-19 vaccines ameliorate viral infection by inducing production of neutralizing antibodies that bind the SARS-CoV-2 Spike protein and inhibit viral cellular entry. However, the clinical effectiveness of these vaccines is transitory as viral variants escape antibody neutralization. Effective vaccines that solely rely upon a T cell response to combat SARS-CoV-2 infection could be transformational because they can utilize highly conserved short pan-variant peptide epitopes, but a mRNA-LNP T cell vaccine has not been shown to provide effective anti-SARS-CoV-2 prophylaxis. Here we show a mRNA-LNP vaccine (MIT-T-COVID) based on highly conserved short peptide epitopes activates CD8[+] and CD4[+] T cell responses that attenuate morbidity and prevent mortality in HLA-A*02:01 transgenic mice infected with SARS-CoV-2 Beta (B.1.351). We found CD8[+] T cells in mice immunized with MIT-T-COVID vaccine significantly increased from 1.1% to 24.0% of total pulmonary nucleated cells prior to and at 7 days post infection (dpi), respectively, indicating dynamic recruitment of circulating specific T cells into the infected lungs. Mice immunized with MIT-T-COVID had 2.8 (2 dpi) and 3.3 (7 dpi) times more lung infiltrating CD8[+] T cells than unimmunized mice. Mice immunized with MIT-T-COVID had 17.4 times more lung infiltrating CD4[+] T cells than unimmunized mice (7 dpi). The undetectable specific antibody response in MIT-T-COVID-immunized mice demonstrates specific T cell responses alone can effectively attenuate the pathogenesis of SARS-CoV-2 infection. Our results suggest further study is merited for pan-variant T cell vaccines, including for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.}, } @article {pmid36968793, year = {2023}, author = {Hashimoto, K}, title = {Overview of the potential use of fluvoxamine for COVID-19 and long COVID.}, journal = {Discover mental health}, volume = {3}, number = {1}, pages = {9}, pmid = {36968793}, issn = {2731-4383}, abstract = {Coronavirus disease 2019 (COVID-19) has presented a serious worldwide threat to public health since its emergence in late 2019. From a safety point of view, drug repurposing has received particular attention. Several clinical studies have demonstrated that the use of fluvoxamine, a selective serotonin reuptake inhibitor with potent sigma-1 receptor agonism, in the early-stage of infection might be associated with the prevention of clinical deterioration in individuals with SARS-CoV-2 infection, although several reports have shown that a low dose of fluvoxamine may be ineffective. There is increasing evidence that SARS-CoV-2 can cross the blood-brain barrier, resulting in a number of psychiatric and neurologic symptoms in COVID-19 survivors. Importantly, about half of COVID-19 survivors experience a variety of long-term sequelae, including psychiatric and neurologic symptoms, known as long COVID. In this priority review, the author presents an overview of the potential use of fluvoxamine in the treatment of COVID-19 and long COVID.}, } @article {pmid36968333, year = {2023}, author = {Sari, DM and Wijaya, LCG}, title = {General rehabilitation for the Post-COVID-19 condition: A narrative review.}, journal = {Annals of thoracic medicine}, volume = {18}, number = {1}, pages = {10-14}, pmid = {36968333}, issn = {1817-1737}, abstract = {COVID-19 significantly impacts the acute phase or the period after being infected by severe acute respiratory syndrome coronavirus-2. Studies have shown it has affected multiorgan and needs continuous care by a multidisciplinary team. Nowadays, guidance is required to assist the recovery process of survivors who reported at least one symptom as a residual effect. This study aims to describe the rehabilitation management of post-COVID-19 conditions. As the number of survivors seems to be increasing, it is expected that COVID-19 survivors will recover through a holistic approach by all physicians. Comprehensive rehabilitation for long COVID or COVID-19-related illnesses includes exercising, nutrition, education, managing voice, breathlessness, neurocognitive problems, mental health, feeding problems, and daily activities. Specific recommendations have already been published to support rehabilitation for survivors in every targeted organ. Supportive care, especially rehabilitation programs, is recently an urgent knowledge in this pandemic.}, } @article {pmid36967698, year = {2023}, author = {Iwasaki, A and Putrino, D}, title = {Why we need a deeper understanding of the pathophysiology of long COVID.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {4}, pages = {393-395}, pmid = {36967698}, issn = {1474-4457}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; }, } @article {pmid36966957, year = {2023}, author = {Mazer, B and Ehrmann Feldman, D}, title = {Functional Limitations in Individuals With Long COVID.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {9}, pages = {1378-1384}, pmid = {36966957}, issn = {1532-821X}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; Health Status ; Self Care ; }, abstract = {OBJECTIVES: To examine the extent of long-term functional deficits experienced by individuals hospitalized for coronavirus disease 2019 (COVID-19). Specific objectives were to (1) describe changes in perceived global health, mobility, participation in daily activities, and employment status from pre-COVID-19 to ≥2 months after infection and (2) evaluate factors associated with change in function.

DESIGN: We conducted a telephone survey (at least 2 months postinfection).

SETTING: Population-based study of adults living at home.

PARTICIPANTS: Adult residents in Laval, Quebec (n=121), who were discharged home posthospitalization for COVID-19.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participants responded to a standard questionnaire (COVID-19 Yorkshire Rehabilitation Screen) regarding persistent symptoms and limitations in daily functioning. We calculated the prevalence of changes in perceived global health, mobility, personal care, participation in daily activities, and employment, and evaluated associated factors using bivariate analysis and multivariable logistic regression.

RESULTS: Almost all participants (94%) were more fatigued and reported deterioration of their global health status (90%) at least 3 months after infection. The majority were more short of breath and experienced pain and anxiety. The change in outcomes indicates a substantial reduction in those reporting "good" health status, mobility, personal care, and daily activities and less employment. Time since diagnosis was significantly associated with global health, mobility, and participation in daily activities.

CONCLUSIONS: This population-based study suggests that individuals hospitalized for COVID-19 infection have symptoms that affect daily functional activities many months after infection. It is imperative that the effect of infection be better understood so that those affected long term can receive the needed services.}, } @article {pmid36966955, year = {2023}, author = {Gradidge, PJ and Torres, G and Constantinou, D and Zanwar, PP and Pinto, SM and Negm, A and Heyn, PC and , }, title = {Exercise Reporting Template for Long COVID Patients: A Rehabilitation Practitioner Guide.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {6}, pages = {991-995}, pmid = {36966955}, issn = {1532-821X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise ; Disease Progression ; }, } @article {pmid36966620, year = {2023}, author = {Kieseler, ML and Duchaine, B}, title = {Persistent prosopagnosia following COVID-19.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {162}, number = {}, pages = {56-64}, pmid = {36966620}, issn = {1973-8102}, mesh = {Humans ; Female ; Adult ; *Prosopagnosia/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Face ; Recognition, Psychology ; Pattern Recognition, Visual ; }, abstract = {COVID-19 can cause psychological problems including loss of smell and taste, long-lasting memory, speech, and language impairments, and psychosis. Here, we provide the first report of prosopagnosia following symptoms consistent with COVID-19. Annie is a 28-year-old woman who had normal face recognition prior to contracting COVID-19 in March 2020. Two months later, she noticed face recognition difficulties while experiencing symptom relapses and her deficits with faces have persisted. On two tests of familiar face recognition and two tests of unfamiliar face recognition, Annie showed clear impairments. In contrast, she scored normally on tests assessing face detection, face identity perception, object recognition, scene recognition, and non-visual memory. Navigational deficits frequently co-occur with prosopagnosia, and Annie reports that her navigational abilities are substantially worse than before she became ill. Self-report survey data from 54 respondents with long COVID showed that a majority reported reductions in visual recognition and navigation abilities. In summary, Annie's results indicate that COVID-19 can produce severe and selective neuropsychological impairments similar to deficits seen following brain damage, and it appears that high-level visual impairments are not uncommon in people with long COVID.}, } @article {pmid36966460, year = {2023}, author = {Perez Giraldo, GS and Ali, ST and Kang, AK and Patel, TR and Budhiraja, S and Gaelen, JI and Lank, GK and Clark, JR and Mukherjee, S and Singer, T and Venkatesh, A and Orban, ZS and Lim, PH and Jimenez, M and Miller, J and Taylor, C and Szymanski, AL and Scarpelli, J and Graham, EL and Balabanov, RD and Barcelo, BE and Cahan, JG and Ruckman, K and Shepard, AG and Slutzky, MW and LaFaver, K and Kumthekar, PU and Shetty, NK and Carroll, KS and Ho, SU and Lukas, RV and Batra, A and Liotta, EM and Koralnik, IJ}, title = {Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.}, journal = {Annals of neurology}, volume = {94}, number = {1}, pages = {146-159}, pmid = {36966460}, issn = {1531-8249}, support = {K23 AG078705/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Prospective Studies ; Quality of Life ; Fatigue/etiology ; }, abstract = {OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.}, } @article {pmid36966161, year = {2023}, author = {Abu Hamdh, B and Nazzal, Z}, title = {A prospective cohort study assessing the relationship between long-COVID symptom incidence in COVID-19 patients and COVID-19 vaccination.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {4896}, pmid = {36966161}, issn = {2045-2322}, mesh = {Aged ; Female ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Incidence ; Prospective Studies ; Vaccination ; Dyspnea/epidemiology ; Fatigue/epidemiology ; }, abstract = {Current studies about the long-term effects of COVID-19 show a wide range of symptoms. This prospective cohort study aimed to find the incidence of long-COVID symptoms and the associated risk factors. We followed 669 confirmed COVID-19 patients. Sociodemographic and clinical data were extracted from medical records and collected via semi-structured telephone interviews on days 10, 30, 60, and 90. The incidence of long-COVID symptoms was 41.6% (95% CI 37.8-45.4%). Females [aOR = 1.5 (95% CI 1.1-2.3)], the elderly [aOR = 4.9 (95% CI 2.0-11.3)], and those who required hospitalization [aOR = 5.0 (95% CI 1.3-3.7)] were at a higher risk of developing long-COVID. Patients with dyspnea at day 10 [aOR: 2.4 (95% CI 1.6-3.7] and fatigue at day 60 [aOR: 3.1 (95% CI 1.5-6.3] were also at risk. While non-vaccinated patients were almost seven times more likely to report long-COVID symptoms than vaccinated patients [aOR: 6.9 (95% CI 4.2-11.3)]. In conclusion, long-COVID was common among COVID-19 patients, with higher rates among females, older age groups, hospitalized patients, and those with dyspnea and fatigue, while vaccination provided protection. Interventions should educate health professionals, raise general public awareness about the risks and consequences of Long COVID, and the value of vaccination.}, } @article {pmid36964995, year = {2023}, author = {Haslam, A and Olivier, T and Prasad, V}, title = {The definition of long COVID used in interventional studies.}, journal = {European journal of clinical investigation}, volume = {53}, number = {8}, pages = {e13989}, doi = {10.1111/eci.13989}, pmid = {36964995}, issn = {1365-2362}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: There has been little consensus for a specific definition of long COVID, though several organizations have created varying ones. We sought to examine the definition of long COVID used in ongoing clinical trials.

METHODS: We searched 'long COVID' and related terms on both PubMed and clinicaltrials.gov for randomized studies that either included patients with long COVID or had a persistent or long-term COVID-related outcome and abstracted long COVID definition components.

RESULTS: Of the 92 studies, a laboratory-only confirmed diagnosis of COVID-19 was stipulated in 54.3% (n = 50) studies. We found eight different time durations specified for how long symptoms needed to have occurred, ranging from 4 to 52 weeks, with 12 weeks being the most common (34.8%; n = 32). 35.9% (n = 33) did not specify a time duration. There were 57 different symptoms specified in total, with a median of one symptom identified per study (range 0-32). 8.7% of trials adhered to NICE or WHO definitions.

CONCLUSION: Standardized definitions of long COVID should be applied in studies assessing this condition to unify and harmonize research on this topic.}, } @article {pmid36964860, year = {2023}, author = {Szabo, S and Zayachkivska, O and Hussain, A and Muller, V}, title = {What is really 'Long COVID'?.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {551-557}, pmid = {36964860}, issn = {1568-5608}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Brain ; Post-Acute COVID-19 Syndrome ; China/epidemiology ; }, abstract = {The previous acute respiratory diseases caused by viruses originating from China or the middle east (e.g., SARS, MERS) remained fast developing short diseases without major sequalae or any long-lasting complications. The new COVID-19, on the other hand, not only that it rapidly spread over the world, but some patients never fully recovered or even if they did, a few weeks later started to complain not only of shortness of breath, if any, but general weakness, muscle pains and 'brain fog', i.e., fuzzy memories. Thus, these signs and symptoms were eventually labelled 'long COVID', for which the most widely used definition is 'new signs and symptoms occurring 4-8 weeks after recovering from acute stage of COVID-19'. The other most frequent manifestations associated with long COVID include headache, loss of memory, smell and of hair, nausea, and vomiting. Thus, long COVID is not a simple disease, but complex disorder of several organ systems malfunctioning; hence, it is probably more appropriate to call this a syndrome. The pathogenesis of long COVID syndrome is poorly understood, but initial and persistent vascular endothelial injury that often triggers the formation of microthrombi that if dislodged as emboli, damage several organs, especially in the brain, heart and kidney, by creating microinfarcts. The other major contributory mechanistic factor is the persistent cytokine storm that may last longer in long COVID patients than in others, probably triggered by aggregates of SARS-Co-2 discovered recently in the adrenal cortex, kidney and brain. The prevalence of long COVID is relatively high, e.g., initially varied 3-30%, and recent data indicate that 2.5% of UK population suffers from this syndrome, while in the US 14.7% of acute COVID-19 patients continued to have symptoms longer than 2 months. Thus, the long COVID syndrome deserves to be further investigated, both from clinical and basic research perspectives.}, } @article {pmid36964859, year = {2023}, author = {Muzyka, I and Revenko, O and Kovalchuk, I and Savytska, M and Bekesevych, A and Kasko, R and Zayachkivska, O}, title = {What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {585-595}, pmid = {36964859}, issn = {1568-5608}, mesh = {Animals ; Adult ; Humans ; *Adipose Tissue, Brown/metabolism ; Post-Acute COVID-19 Syndrome ; *COVID-19/metabolism ; Obesity/metabolism ; }, abstract = {Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokines, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomena which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.}, } @article {pmid36964670, year = {2024}, author = {Calcaterra, G and Bassareo, PP and Barilla', F and Mehta, JL}, title = {Letter on the Recent Paper "Vascular 'Long COVID': A New Vessel Disease?".}, journal = {Angiology}, volume = {75}, number = {1}, pages = {98}, doi = {10.1177/00033197231167051}, pmid = {36964670}, issn = {1940-1574}, mesh = {Humans ; *COVID-19 ; *Vascular Diseases/therapy ; }, } @article {pmid36963989, year = {2023}, author = {Nunes, JM and Kell, DB and Pretorius, E}, title = {Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses.}, journal = {Blood reviews}, volume = {60}, number = {}, pages = {101075}, pmid = {36963989}, issn = {1532-1681}, mesh = {Humans ; *Fatigue Syndrome, Chronic/etiology/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS. Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology - including endothelial dysfunction, coagulopathy, and vascular dysregulation - the question of whether or not the same biological abnormalities are of significance in ME/CFS arises. Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation. A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction. Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms. Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens. Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning. Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system. Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes. Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly. This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.}, } @article {pmid36961688, year = {2023}, author = {Einecke, D}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {165}, number = {6}, pages = {18}, doi = {10.1007/s15006-023-2515-x}, pmid = {36961688}, issn = {1613-3560}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36961039, year = {2023}, author = {Šipetić, T and Rajković, D and Bogavac Stanojević, N and Marinković, V and Meštrović, A and Rouse, MJ}, title = {SMART Pharmacists Serving the New Needs of the Post-COVID Patients, Leaving No-One Behind.}, journal = {Pharmacy (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {36961039}, issn = {2226-4787}, abstract = {This study aims to demonstrate the improvements in clinical symptoms in patients with post-COVID syndrome after a community pharmacy-based intervention in Serbia. The Pharmaceutical Chamber of Serbia ("Chamber") invited pharmacists to deliver post-COVID patient care counselling, supported by the SMART Pharmacist Program, offering education and guidance. Present symptoms, duration and patient self-reported severity of symptoms on a scale of 1-5 on the first visit were recorded. After the counselling and proposed self-medication treatment, the time of the follow-up visit and the severity of the recorded symptoms were also recorded. The prospective data collection lasted from December 2021 to September 2022. In total, 871 patients with post-COVID symptoms were included in the study, served by 53 pharmacists. The most frequently reported post-COVID symptoms coincided with the literature, mostly related to the respiratory system (51.2%), immunity status (32.2%), fatigue and exhaustion (30.7%), skin, hair and nails (27.4%) and cognitive functions (27.9%). A total of 26.5% of patients were referred to their family physician (general practitioner), and 69.5% returned to the pharmacist for a follow-up visit. On the first visit, the median severity of patients' symptoms was three, while on the second visit it dropped to one. The pharmacists' intervention led to a significant improvement in the post-COVID patients' condition.}, } @article {pmid36958743, year = {2023}, author = {Liew, F and Efstathiou, C and Openshaw, PJM}, title = {Long COVID: clues about causes.}, journal = {The European respiratory journal}, volume = {61}, number = {5}, pages = {}, pmid = {36958743}, issn = {1399-3003}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Monocytes ; SARS-CoV-2 ; Patient Acuity ; }, abstract = {Many patients report persistent symptoms after resolution of acute COVID-19, regardless of SARS-CoV-2 variant and even if the initial illness is mild [1, 2]. A multitude of symptoms have been described under the umbrella term ‘Long COVID’, otherwise known as ‘post-COVID syndrome’ or ‘post-acute sequelae of SARS-CoV-2 (PASC)’; for simplicity we will use the term Long COVID. Symptoms are diverse but include breathlessness, fatigue and brain fog, reported to affect up to 69% of cases [3]. Long COVID can be debilitating, 45.2% of patients requiring a reduced work schedule [4]. The WHO estimates that 17 million people in Europe have experienced Long COVID during the first two years of the pandemic [5]. SARS-CoV-2 variants continue to circulate and the risk of post-acute complications remains; a recent study of 56 003 UK patients found that even after Omicron infection, 4.5% suffered persistent symptoms [6]. It is therefore likely that Long COVID will provide a substantial medical and economic burden for the foreseeable future. There is an urgent need to understand mechanisms of disease and develop effective treatments based on this understanding.}, } @article {pmid36952419, year = {2023}, author = {Couzin-Frankel, J}, title = {New Long Covid cases decline with Omicron.}, journal = {Science (New York, N.Y.)}, volume = {379}, number = {6638}, pages = {1174-1175}, doi = {10.1126/science.adh9054}, pmid = {36952419}, issn = {1095-9203}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome/epidemiology/prevention & control/virology ; *Vaccination ; *SARS-CoV-2 ; }, abstract = {Virus biology, widespread vaccination may be driving down risk of persistent symptoms.}, } @article {pmid36952147, year = {2023}, author = {Kazama, I}, title = {Brain Leukocytes as the Potential Therapeutic Target for Post-COVID-19 Brain Fog.}, journal = {Neurochemical research}, volume = {48}, number = {8}, pages = {2345-2349}, pmid = {36952147}, issn = {1573-6903}, support = {2218//Salt Science Research Foundation/ ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Leukocytes ; Inflammation ; Anti-Bacterial Agents ; Brain ; }, abstract = {After recovering from the acute phase of coronavirus disease 2019 (COVID-19), many patients struggle with additional symptoms of long COVID during the chronic phase. Among them, the neuropsychiatric manifestations characterized by a short-term memory loss and inability to concentrate are called "brain fog". Recent studies have revealed the involvement of "chronic neuro-inflammation" in the pathogenesis of brain fog following COVID-19 infection. In the COVID-related brain fog, similarly to neurodegenerative disorders caused by neuro-inflammation, brain leukocytes, such as microglia and lymphocytes, are hyperactivated, suggesting the overexpression of delayed rectifier K[+]-channels (Kv1.3) within the cells. In our previous patch-clamp studies, drugs, such as antihistamines, statins, nonsteroidal anti-inflammatory drugs, antibiotics and anti-hypertensive drugs, suppressed the Kv1.3-channel activity and reduced the production of pro-inflammatory cytokines. Additionally, newer generation antihistamines, antibiotics and corticosteroids strongly stabilize mast cells that directly activate microglia in the brain. Taking such pharmacological properties of these commonly used drugs into account, they may be useful in the treatment of COVID-related brain fog, in which the enhanced innate and adaptive immune responses are responsible for the pathogenesis.}, } @article {pmid36951877, year = {2023}, author = {Chen, LL and van de Burgt, A and Smit, F and Audhoe, RS and de Boer, SM and van Velden, FHP and de Geus-Oei, LF}, title = {Investigating the potential added value of [ 18 F]FDG-PET/CT in long COVID patients with persistent symptoms: a proof of concept study.}, journal = {Nuclear medicine communications}, volume = {44}, number = {6}, pages = {495-501}, pmid = {36951877}, issn = {1473-5628}, mesh = {Humans ; *Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Post-Acute COVID-19 Syndrome ; Proof of Concept Study ; Prospective Studies ; Myalgia ; *COVID-19/diagnostic imaging ; Tomography, X-Ray Computed ; Radiopharmaceuticals ; }, abstract = {OBJECTIVE: Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [ 18 F]FDG-PET/computed tomography (CT) for this group of long COVID patients.

METHODS: For this proof of concept study, we evaluated [ 18 F]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann-Whitney U -test was performed to find significant differences between the two groups.

RESULTS: Thirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P  < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment.

CONCLUSION: As we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [ 18 F]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID.}, } @article {pmid36951829, year = {2023}, author = {Xie, Y and Choi, T and Al-Aly, Z}, title = {Association of Treatment With Nirmatrelvir and the Risk of Post-COVID-19 Condition.}, journal = {JAMA internal medicine}, volume = {183}, number = {6}, pages = {554-564}, pmid = {36951829}, issn = {2168-6114}, mesh = {Male ; United States/epidemiology ; Humans ; Middle Aged ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; Cohort Studies ; Antiviral Agents/therapeutic use ; Disease Progression ; }, abstract = {IMPORTANCE: Post-COVID-19 condition (PCC), also known as long COVID, affects many individuals. Prevention of PCC is an urgent public health priority.

OBJECTIVE: To examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of PCC.

This cohort study used the health care databases of the US Department of Veterans Affairs (VA) to identify patients who had a SARS-CoV-2 positive test result between January 3, 2022, and December 31, 2022, who were not hospitalized on the day of the positive test result, who had at least 1 risk factor for progression to severe COVID-19 illness, and who had survived the first 30 days after SARS-CoV-2 diagnosis. Those who were treated with oral nirmatrelvir within 5 days after the positive test (n = 35 717) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n = 246 076) were identified.

EXPOSURES: Treatment with nirmatrelvir or receipt of no COVID-19 antiviral or antibody treatment based on prescription records.

MAIN OUTCOMES AND MEASURES: Inverse probability weighted survival models were used to estimate the association of nirmatrelvir (vs control) with post-acute death, post-acute hospitalization, and a prespecified panel of 13 post-acute COVID-19 sequelae (components of PCC) and reported in relative scale as relative risk (RR) or hazard ratio (HR) and in absolute scale as absolute risk reduction in percentage at 180 days (ARR).

RESULTS: A total of 281 793 patients (mean [SD] age, 61.99 [14.96]; 242 383 [86.01%] male) who had a positive SARS-CoV-2 test result and had at least 1 risk factor for progression to severe COVID-19 illness were studied. Among them, 246 076 received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection, and 35 717 received oral nirmatrelvir within 5 days after the positive SARS-CoV-2 test result. Compared with the control group, nirmatrelvir was associated with reduced risk of PCC (RR, 0.74; 95% CI, 0.72-0.77; ARR, 4.51%; 95% CI, 4.01-4.99), including reduced risk of 10 of 13 post-acute sequelae (components of PCC) in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (pulmonary embolism and deep vein thrombosis), fatigue and malaise, acute kidney disease, muscle pain, neurologic system (neurocognitive impairment and dysautonomia), and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR, 0.53; 95% CI, 0.46-0.61); ARR, 0.65%; 95% CI, 0.54-0.77), and post-acute hospitalization (HR, 0.76; 95% CI, 0.73-0.80; ARR, 1.72%; 95% CI, 1.42-2.01). Nirmatrelvir was associated with reduced risk of PCC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection.

CONCLUSIONS AND RELEVANCE: This cohort study found that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe disease, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test result was associated with reduced risk of PCC across the risk spectrum in this cohort and regardless of vaccination status and history of prior infection; the totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 may reduce the risk of post-acute adverse health outcomes.}, } @article {pmid36950279, year = {2023}, author = {Stefanou, E and Karvelas, N and Bennett, S and Kole, C}, title = {Cerebrovascular Manifestations of SARS-CoV-2: A Comprehensive Review.}, journal = {Current treatment options in neurology}, volume = {25}, number = {4}, pages = {71-92}, pmid = {36950279}, issn = {1092-8480}, abstract = {PURPOSE OF REVIEW: The risks of cerebrovascular manifestations due to SARS-CoV-2 infection are significantly increased within the first 6 months of the infection. Our work aims to give an update on current clinical aspects of diagnosis and treatment of cerebrovascular manifestations during acute and long-term SARS-CoV-2 infection.

RECENT FINDINGS: The incidence of acute ischemic stroke and haemorrhagic stroke during acute SARS-CoV-2 patients is estimated at 0.9 to 4.6% and 0.5-0.9%, respectively, and were associated with increased mortality. The majority presented with hemiparesis, dysarthria, sensory deficits, and a NIHSS score within 5-15. In addition, beyond the first 30 days of infection people with COVID-19 exhibited increased risk of stroke. During acute phase, age, hypertension, diabetes, and medical history of vascular disease were increased in patients with COVID-19 with new onset of cerebrovascular manifestations, while during long-COVID-19, the risk of cerebrovascular manifestations were found increased regardless of these factors. The management of patients with large-vessel ischemic stroke fulfilling the intravenous thrombolysis criteria are successfully treated according to the guidelines, while hyperosmolar therapy is typically administered in 4- to 6-h intervals. In addition, prophylaxis of anticoagulation therapy is associated with a better prognosis and low mortality during acute and post hospital discharge of patients with COVID-19.

SUMMARY: In this work, we provide a comprehensive review of the current literature on acute and post-acute COVID-19 cerebrovascular sequelae, symptomatology, and its pathophysiology mechanisms. Moreover, we discuss therapeutic strategies for these patients during acute and long-term care and point populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease are more likely to develop cerebrovascular complications.}, } @article {pmid36949968, year = {2023}, author = {Kirkpatrick, K and Khan, MH and Deng, Y and Shah, KB}, title = {A Review of Stellate Ganglion Block as an Adjunctive Treatment Modality.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35174}, pmid = {36949968}, issn = {2168-8184}, abstract = {Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article. This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade.}, } @article {pmid36949773, year = {2023}, author = {Ng, TKS and Dal Bello-Haas, V and Negm, A and Philippou, E and Santos, FH and Heyn, PC}, title = {Editorial: Post-Acute Sequelae of COVID-19 infection (PASC): Implications for geriatric and neurological care.}, journal = {Frontiers in aging neuroscience}, volume = {15}, number = {}, pages = {1168720}, pmid = {36949773}, issn = {1663-4365}, } @article {pmid36949439, year = {2023}, author = {Mastrorosa, I and Del Duca, G and Pinnetti, C and Lorenzini, P and Vergori, A and Brita, AC and Camici, M and Mazzotta, V and Baldini, F and Chinello, P and Mencarini, P and Giancola, ML and Abdeddaim, A and Girardi, E and Vaia, F and Antinori, A}, title = {What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis.}, journal = {Health and quality of life outcomes}, volume = {21}, number = {1}, pages = {28}, pmid = {36949439}, issn = {1477-7525}, mesh = {Humans ; Female ; *Quality of Life ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors.

METHODS: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL.

RESULTS: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS.

CONCLUSIONS: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.}, } @article {pmid36948566, year = {2023}, author = {Lüscher, J and Scholz, U and Bierbauer, W}, title = {Social support, distress and well-being in individuals experiencing Long-COVID: a cross-sectional survey study.}, journal = {BMJ open}, volume = {13}, number = {3}, pages = {e067166}, pmid = {36948566}, issn = {2044-6055}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Depression/epidemiology/psychology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Anxiety/epidemiology/psychology ; Social Support ; }, abstract = {OBJECTIVES: Increasingly attention of the COVID-19 pandemic is directed towards its long-term effects, also known as Long-COVID. So far, Long-COVID was examined mainly from a medical perspective, leaving psychosocial effects of Long-COVID understudied. The present study advances the current literature by examining social support in the context of Long-COVID. The study not only examines received support reported by individuals with Long-COVID, but also provided support reported by relatives of individuals with Long-COVID.

DESIGN: Cross-sectional study.

SETTING: The study was conducted from June to October 2021 in Austria, Germany and the German-speaking part of Switzerland.

PARTICIPANTS: We examined 256 individuals with Long-COVID (MAge=45.05 years, 90.2% women) and 50 relatives of individuals with Long-COVID (MAge=48.34 years, 66.1% female) in two separate online surveys, assessing social support, well-being and distress.

PRIMARY OUTCOME MEASURES: Primary outcomes were positive and negative affect, anxiety and depressive symptoms and perceived stress.

RESULTS: For individuals with Long-COVID, receiving emotional support was related to higher well-being (positive affect: b=0.29, p<0.01; negative affect: b=-0.31, p<0.05) and less distress (anxiety: b=-1.45, p<0.01; depressive symptoms: b=-1.04, p<0.05; perceived stress: b=-0.21, p<0.05) but no effects emerged for receiving practical support. For relatives of individuals with Long-COVID, providing emotional support was only related to lower depressive symptoms (b=-2.57, p<0.05). Again, provided practical support was unrelated to the outcomes considered.

CONCLUSIONS: Emotional support is likely to play an important role in well-being and distress of patients and relatives, whereas practical support does not seem to make a difference. Future research should clarify under what conditions different kinds of support unfold their positive effects on well-being and distress in the context of Long-COVID.}, } @article {pmid36948378, year = {2023}, author = {Gross, M and Lansang, NM and Gopaul, U and Ogawa, EF and Heyn, PC and Santos, FH and Sood, P and Zanwar, PP and Schwertfeger, J and Faieta, J}, title = {What Do I Need to Know About Long-Covid-related Fatigue, Brain Fog, and Mental Health Changes?.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {6}, pages = {996-1002}, pmid = {36948378}, issn = {1532-821X}, support = {IK1 RX003636/RX/RRD VA/United States ; }, mesh = {Humans ; *Mental Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Fatigue/etiology ; Brain ; }, } @article {pmid36947300, year = {2023}, author = {Muzyka, I and Yakhnytska, M and Savytska, M and Zayachkivska, O}, title = {Long COVID prevalence and physiology-centered risks: population-based study in Ukraine.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {597-602}, pmid = {36947300}, issn = {1568-5608}, mesh = {Adult ; Male ; Humans ; Female ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Ukraine/epidemiology ; Cohort Studies ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {AIM: Multifaceted long COVID caused by SARS-COV-2 affects all populations in the World and takes priority over any other research topics for health care. The purpose of study is to identify physiology-centered risks, prevalence, symptoms and laboratory findings in patients with long COVID in Ukraine.

METHODS: A prospective, cohort study was carried out on 332 patients with long COVID after 4 weeks and more after acute infection COVID-19 from Jul 1, 2021, to Jul 1, 2022. Physiology-centered risks related to age, gender, body mass index (BMI), marital status and educational capacity, smoking, lifestyle, physical activity, and laboratory findings (before disease), and symptom distribution were analyzed.

RESULTS: The cohort for the study consisted of 166 females and 107 males (mean age = 42; including young 18 (5.4%) and middle- and old-aged adults 314 (96.4%)). Increased BMI was in 61%, and less physical activity-65%. There were 4 clusters of symptoms related to physical, neurocognitive, pulmonary, and pain conditions. 95% of participants had ≥ 3 symptoms. The most common symptoms were fatigue (90%), muscular pain (85%), anosmia (70%), hair loss (70%), sleep disorders (70%), dyspnea (30%), and brain fog (25%). Among laboratory finding increased CRP (92.6%) and fibrinogen (82.7%) dominated. There are no differences between hospitalized and non-hospitalized patients in distribution symptoms.

CONCLUSIONS: The prevalence of long COVID is 23%, and its physiology-centered risk factors are related to age more 38 years, female sex, unhealthy lifestyle, increased BMI, and increased inflammatory markers during COVID-19. The most common symptoms are associated with neurocognitive and pain clusters.}, } @article {pmid36947108, year = {2023}, author = {Sherif, ZA and Gomez, CR and Connors, TJ and Henrich, TJ and Reeves, WB and , }, title = {Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36947108}, issn = {2050-084X}, support = {K08 HL141623/HL/NHLBI NIH HHS/United States ; K23 AI141686/AI/NIAID NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Autoimmunity ; Blood Coagulation ; Disease Progression ; }, abstract = {COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.}, } @article {pmid36946597, year = {2023}, author = {Lenze, EJ and Reiersen, AM and Zorumski, CF and Santosh, PJ}, title = {Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer.}, journal = {The Journal of clinical psychiatry}, volume = {84}, number = {3}, pages = {}, doi = {10.4088/JCP.22r14494}, pmid = {36946597}, issn = {1555-2101}, mesh = {*Drug Repositioning ; *COVID-19/complications ; *Alzheimer Disease/drug therapy ; *Neoplasms/drug therapy ; *COVID-19 Drug Treatment ; *Mental Disorders/complications/drug therapy ; Humans ; Animals ; Fluvoxamine/therapeutic use ; *Psychotropic Drugs/therapeutic use ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Post-Acute COVID-19 Syndrome/complications/drug therapy ; }, abstract = {Importance: "Psychotropic" drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact. Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine's use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer's disease, cancer, and other conditions. Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.}, } @article {pmid36945569, year = {2023}, author = {Foo, SS and Chen, W and Jung, KL and Azamor, T and Choi, UY and Zhang, P and Comhair, SA and Erzurum, SC and Jehi, L and Jung, JU}, title = {Immunometabolic rewiring in long COVID patients with chronic headache.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.06.531302}, pmid = {36945569}, issn = {2692-8205}, support = {R35 CA200422/CA/NCI NIH HHS/United States ; }, abstract = {Almost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache. Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.}, } @article {pmid36944811, year = {2023}, author = {Nobili, A and D'Avanzo, B and Tettamanti, M and Galbussera, AA and Remuzzi, G and Fortino, I and Leoni, O and Harari, S and Mannucci, PM}, title = {Post-COVID condition: dispensation of drugs and diagnostic tests as proxies of healthcare impact.}, journal = {Internal and emergency medicine}, volume = {18}, number = {3}, pages = {801-809}, pmid = {36944811}, issn = {1970-9366}, support = {DGR n. 3375 - July 14//Regione Lombardia/ ; 2020//Regione Lombardia/ ; }, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Delivery of Health Care ; Diagnostic Tests, Routine ; COVID-19 Testing ; }, abstract = {With the goal to increase knowledge on the healthcare impact of the post-COVID-19 condition we exploited the administrative claims database of Lombardy, the largest Italian region and the first after China to be heavily hit by the SARS-CoV-2 pandemic in February-May 2020. We chose to employ the dispensation of drugs and diagnostic tests as proxies of the impact of the post-COVID condition in 46,574 cases who recovered from COVID-19 and were negative at PCR testing within June 20, 2020. Data were obtained throughout the 18-month post-negativization period until December 2021 and results on the use of drugs and diagnostic tests were compared with those accrued in the same cases during the pre-COVID period in July-December 2019. After an increase in the first semester after SARS-CoV-2 negativization (July-December 2020), trends in the dispensation of drugs according to the broad ATC classes and of diagnostic tests decreased or remained substantially stable. However, dispensation of drugs for acid related disorders (A02), diabetes (A10), heparins (B01AB), direct oral anticoagulants (B01AP), antipsychotics (N05A), antidepressants (N06A) and for obstructive airways diseases (R03) was still higher than in the pre-COVID period. These findings, based upon drug and diagnostic test dispensation as proxies of the healthcare impact of the post-COVID condition, show that in a substantial proportion of recovered cases the post-COVID condition is active and clinically relevant 18 months after the acute disease. The findings also provide indirect evidence of the body organs and systems more compromised in the post-COVID period.}, } @article {pmid36944437, year = {2023}, author = {Salisbury, H}, title = {Helen Salisbury: Unexplained symptoms aren't always long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {654}, doi = {10.1136/bmj.p654}, pmid = {36944437}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36944213, year = {2023}, author = {Descatha, A and Evanoff, BA and Fadel, M}, title = {Post-COVID condition or "long COVID", return-to work, and occupational health research.}, journal = {Scandinavian journal of work, environment & health}, volume = {49}, number = {3}, pages = {165-169}, pmid = {36944213}, issn = {1795-990X}, support = {U19 OH008868/OH/NIOSH CDC HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Occupational Health ; *COVID-19 ; *Mental Disorders ; Return to Work ; }, } @article {pmid36943909, year = {2023}, author = {Rinn, R and Gao, L and Schoeneich, S and Dahmen, A and Anand Kumar, V and Becker, P and Lippke, S}, title = {Digital Interventions for Treating Post-COVID or Long-COVID Symptoms: Scoping Review.}, journal = {Journal of medical Internet research}, volume = {25}, number = {}, pages = {e45711}, pmid = {36943909}, issn = {1438-8871}, mesh = {Adult ; Humans ; *COVID-19 ; Health Personnel ; Mental Health ; *Post-Acute COVID-19 Syndrome/rehabilitation ; *Telerehabilitation ; }, abstract = {BACKGROUND: Patients with post-COVID/long-COVID symptoms need support, and health care professionals need to be able to provide evidence-based patient care. Digital interventions can meet these requirements, especially if personal contact is limited.

OBJECTIVE: We reviewed evidence-based digital interventions that are currently available to help manage physical and mental health in patients with post-COVID/long-COVID symptoms.

METHODS: A scoping review was carried out summarizing novel digital health interventions for treating post-COVID/long-COVID patients. Using the PICO (population, intervention, comparison, outcome) scheme, original studies were summarized, in which patients with post-COVID/long-COVID symptoms used digital interventions to help aid recovery.

RESULTS: From all scanned articles, 8 original studies matched the inclusion criteria. Of the 8 studies, 3 were "pretest" studies, 3 described the implementation of a telerehabilitation program, 1 was a post-COVID/long-COVID program, and 1 described the results of qualitative interviews with patients who used an online peer-support group. Following the PICO scheme, we summarized previous studies. Studies varied in terms of participants (P), ranging from adults in different countries, such as former hospitalized patients with COVID-19, to individuals in disadvantaged communities in the United Kingdom, as well as health care workers. In addition, the studies included patients who had previously been infected with COVID-19 and who had ongoing symptoms. Some studies focused on individuals with specific symptoms, including those with either post-COVID-19 or long-term symptoms, while other studies included patients based on participation in online peer-support groups. The interventions (I) also varied. Most interventions used a combination of psychological and physical exercises, but they varied in duration, frequency, and social dimensions. The reviewed studies investigated the physical and mental health conditions of patients with post-COVID/long-COVID symptoms. Most studies had no control (C) group, and most studies reported outcomes (O) or improvements in physiological health perception, some physical conditions, fatigue, and some psychological aspects such as depression. However, some studies found no improvements in bowel or bladder problems, concentration, short-term memory, unpleasant dreams, physical ailments, perceived bodily pain, emotional ailments, and perceived mental health.

CONCLUSIONS: More systematic research with larger sample sizes is required to overcome sampling bias and include health care professionals' perspectives, as well as help patients mobilize support from health care professionals and social network partners. The evidence so far suggests that patients should be provided with digital interventions to manage symptoms and reintegrate into everyday life, including work.}, } @article {pmid36943643, year = {2023}, author = {Tak, CR}, title = {The health impact of long COVID: a cross-sectional examination of health-related quality of life, disability, and health status among individuals with self-reported post-acute sequelae of SARS CoV-2 infection at various points of recovery.}, journal = {Journal of patient-reported outcomes}, volume = {7}, number = {1}, pages = {31}, pmid = {36943643}, issn = {2509-8020}, support = {UL1 TR002538/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Humans ; *Quality of Life/psychology ; Post-Acute COVID-19 Syndrome ; Self Report ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Health Status ; }, abstract = {OBJECTIVE: The novel Coronavirus (COVID-19) has continued to present a significant burden to global public health efforts. The purpose of this study was to estimate the health-related quality of life, disability, and health status of individuals with self-reported long COVID at various lengths of recovery.

METHODS: We conducted a cross-sectional online survey of individuals with self-reported long COVID. Participants were asked to complete the five-item EuroQOL EQ-5D-5L and EQ visual analog scale, the 12-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 and the 10-item Patient Reported Outcome Measurement Information System (PROMIS) Global Health v1.2 short form. Descriptive and inferential statistics were used to characterize the responses and differences across groups.

RESULTS: Eighty-two participants from 13 countries completed the EQ-5D-5L, 73 completed the WHODAS 2.0 and 80 participants completed the PROMIS. The mean EQ-5D-5L utility score was 0.51. The mean WHODAS score was 49.0. In the previous 30 days, participants reported their symptoms affected them for a mean of 24 days, they were totally unable to carry out usual activities for 15 days, and they cut back or reduced activities for 26 days. The mean PROMIS physical health and mental health scores were 10.7 and 8.6, respectively, corresponding to below-average health. No significant differences were detected across time or according to severity of acute infection.

CONCLUSIONS: Long COVID presents a significant chronic health burden to adults in the US and abroad. This health burden may persist for many months post-acute infection.}, } @article {pmid36943540, year = {2023}, author = {Muzyka, I and Revenko, O and Kovalchuk, I and Savytska, M and Bekesevych, A and Zayachkivska, O}, title = {What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {1-9}, pmid = {36943540}, issn = {1568-5608}, abstract = {Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.}, } @article {pmid36943516, year = {2023}, author = {Schneider, SA and Desai, S and Phokaewvarangkul, O and Rosca, EC and Sringean, J and Anand, P and Bravo, GÁ and Cardoso, F and Cervantes-Arslanian, AM and Chovatiya, H and Crosiers, D and Dijkstra, F and Fearon, C and Grandas, F and Guedj, E and Méndez-Guerrero, A and Hassan, M and Jankovic, J and Lang, AE and Makhoul, K and Muccioli, L and O'Shea, SA and Ostovan, VR and Perez-Sanchez, JR and Ramdhani, R and Ros-Castelló, V and Schulte, C and Shah, P and Wojtecki, L and Pal, PK}, title = {COVID19-associated new-onset movement disorders: a follow-up study.}, journal = {Journal of neurology}, volume = {270}, number = {5}, pages = {2409-2415}, pmid = {36943516}, issn = {1432-1459}, mesh = {Male ; Female ; Humans ; Aged ; *COVID-19/complications ; Follow-Up Studies ; *Movement Disorders/etiology ; Risk Factors ; Tremor/complications ; }, abstract = {BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited.

METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed.

RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence.

CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.}, } @article {pmid36943067, year = {2023}, author = {Morón-López, S and Riveira-Muñoz, E and Urrea, V and Gutiérrez-Chamorro, L and Ávila-Nieto, C and Noguera-Julian, M and Carrillo, J and Mitjà, O and Mateu, L and Massanella, M and Ballana, E and Martinez-Picado, J}, title = {Comparison of Reverse Transcription (RT)-Quantitative PCR and RT-Droplet Digital PCR for Detection of Genomic and Subgenomic SARS-CoV-2 RNA.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0415922}, pmid = {36943067}, issn = {2165-0497}, abstract = {Most individuals acutely infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit mild symptoms. However, 10 to 20% of those infected develop long-term symptoms, referred to as post-coronavirus disease 2019 (COVID-19) condition (PCC). One hypothesis is that PCC might be exacerbated by viral persistence in tissue sanctuaries. Therefore, the accurate detection and quantification of SARS-CoV-2 are not only necessary for viral load monitoring but also crucial for detecting long-term viral persistence and determining whether viral replication is occurring in tissue reservoirs. In this study, the sensitivity and robustness of reverse transcription (RT)-droplet digital PCR (ddPCR) and RT-quantitative PCR (qPCR) techniques have been compared for the detection and quantification of SARS-CoV-2 genomic and subgenomic RNAs from oropharyngeal swabs taken from confirmed SARS-CoV-2-positive, SARS-CoV-2-exposed, and nonexposed individuals as well as from samples from mice infected with SARS-CoV-2. Our data demonstrated that both techniques presented equivalent results in the mid- and high-viral-load ranges. Additionally, RT-ddPCR was more sensitive than RT-qPCR in the low-viral-load range, allowing the accurate detection of positive results in individuals exposed to the virus. Overall, these data suggest that RT-ddPCR might be an alternative to RT-qPCR for detecting low viral loads in samples and for assessing viral persistence in samples from individuals with PCC. IMPORTANCE We developed one-step reverse transcription (RT)-droplet digital PCR (ddPCR) protocols to detect SARS-CoV-2 RNA and compared them to the gold-standard RT-quantitative PCR (RT-qPCR) method. RT-ddPCR was more sensitive than RT-qPCR in the low-viral-load range, while both techniques were equivalent in the mid- and high-viral-load ranges. Overall, these results suggest that RT-ddPCR might be a viable alternative to RT-qPCR when it comes to detecting low viral loads in samples, which is a highly relevant issue for determining viral persistence in as-yet-unknown tissue reservoirs in individuals suffering from post-COVID conditions or long COVID.}, } @article {pmid36942996, year = {2023}, author = {Veliz, PT and Zhou, W and Smith, S and Larson, JL}, title = {Substance Use and the Self-Management of Persistent Symptoms of COVID-19.}, journal = {Substance use & misuse}, volume = {58}, number = {6}, pages = {835-840}, doi = {10.1080/10826084.2023.2184208}, pmid = {36942996}, issn = {1532-2491}, mesh = {Adult ; Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *Self-Management ; *Substance-Related Disorders/therapy ; *Cannabis ; *Hallucinogens ; }, abstract = {Background: Understanding the self-management practices of persistent symptoms of SARS-Cov-2 (COVID-19) is critical given the misinformation that has been presented about this disease in the U.S. The purpose of this descriptive study is to assess the self-management of persistent symptoms of COVID-19 with commonly used and misused substances (i.e., alcohol, marijuana and commonly prescribed medications) among adults in the U.S. Methods: The data for this study comes from a cross-sectional survey of U.S. adults that was designed to broadly assess symptom burden, persistent symptom patterns, self-efficacy for symptom management and self-management strategies among people who experienced persistent/Long COVID. Multiple logistic regression analyses were used to assess how symptom length of COVID-19 was associated with the use of several substances to manage these persistent symptoms. Results: The analysis found that adults who had COVID-19 symptoms that persisted for 13 weeks or longer had higher rates of using alcohol (27.3%), marijuana (30.9%) and prescription tranquilizers (21.4%) to manage these symptoms when compared to their adult peers who had COVID-19 symptoms persist for only 4 weeks or less. For instance, the odds of indicating the use of marijuana (AOR = 4.21 95% CI = 1.68,10.5) to manage COVID-19 related symptoms was roughly four times higher for respondents who had COVID-19 symptoms persist for 13 weeks or longer when compared to respondents whose COVID-19 symptoms persisted for only 4 weeks or less. Conclusion: The findings suggest that screening of substance use disorders should be considered among healthcare providers who are treating adults who have persistent symptoms of COVID-19.}, } @article {pmid36942191, year = {2023}, author = {Kitsos, D and Tzartos, J and Korres, G and Giannopapas, V and Riga, M and Stergiou, C and Tsoga, A and Grigoropoulos, C and Paraskevas, G and Zompola, C and Nikolopoulos, T and Giannopoulos, S}, title = {IL-6 Serum Levels in COVID-19 Patients With Vertigo.}, journal = {Cureus}, volume = {15}, number = {2}, pages = {e35042}, pmid = {36942191}, issn = {2168-8184}, abstract = {Introduction Dizziness and vertigo represent well-established symptoms of COVID-19. An overexpression of cytokines, a condition often described with the term "cytokine storm" or "hypercytokinemia", is a key characteristic of SARS-Cov-2 infection and plays a pivotal role in disease progression and prognosis. Among them, IL-6 is of major importance. Purpose The purpose of this study is to investigate any probable IL-6 serum titer difference in COVID-19 patients with vertigo (V+) or without vertigo (V-) admitted to the COVID-19 internal medicine departments of Attikon University Hospital, Athens, Greece, within 12 months. Methods The sample consisted of 52 COVID-19 patients who were diagnosed between January 1, 2020, and December 31, 2020. Of those, 31 reported vertigos during their admission (V+), while the remaining 21 COVID-19 patients did not complain of such symptoms (V-). Results Higher IL-6 serum levels post-COVID-19 infections lead to higher incidence rates of vertigo symptoms (p<.005), regardless of gender and age (p.005).}, } @article {pmid36941374, year = {2023}, author = {Skilbeck, L and Spanton, C and Paton, M}, title = {Patients' lived experience and reflections on long COVID: an interpretive phenomenological analysis within an integrated adult primary care psychology NHS service.}, journal = {Journal of patient-reported outcomes}, volume = {7}, number = {1}, pages = {30}, pmid = {36941374}, issn = {2509-8020}, mesh = {Humans ; Adult ; *Post-Acute COVID-19 Syndrome ; State Medicine ; *COVID-19 ; Qualitative Research ; Primary Health Care ; }, abstract = {BACKGROUND: Long Covid is an unknown illness which has been shown to affect sufferers regardless of mild initial COVID-19 or age. There is still a lot unknown about long COVID illness. There has been a call to understand this illness not only from a professional standpoint but also through the lived experience of patients. Patient reported outcomes through lived experience research is one such angle. To date, no research has explored the overall lived experiences and long COVID illness trajectory perspectives of the patients. This study aimed to gather patient reported outcomes of their long COVID through lived experience research. It recruited adult participants aged 18-years and over who had been referred to a primary care integrated psychology service. The study employed qualitative research using semi-structured interviews and Interpretive Phenomenological Analysis methodology.

RESULTS: A total of eighteen participants completed the study. From their lived experiences, the participants uncovered the varied symptoms of long COVID. They also uncovered their lived progression of living with an unknown chronic illness. Common themes included uncertainty, mental and social impacts, and the processes of self-advocacy, mastering their symptoms, subjective recovery and future coping.

CONCLUSION: This study uncovered the lived experience of long COVID in participants. The results from this study uncovered the lived subjective biopsychosocial experiences of long COVID chronic illness. Traditionally, patients receive care and recommendations from healthcare professionals. However, as long COVID is a new illness, this care model was limited. The participants in the current study described being left with a sense of uncertainty and role confusion. However, participants were able to realize their locus of control over their long COVID illness progression. This illustrates that patients have the resources to uncover the unknowns of this new illness which could inform clinical practice and further research. This suggests that that long COVID needs to be approached from a biopsychosocial perspective which emphasises patient involvement.}, } @article {pmid36938946, year = {2023}, author = {Buonsenso, D and Morello, R and Mariani, F and De Rose, C and Mastrantoni, L and Zampino, G and Valentini, P}, title = {Risk of long Covid in children infected with Omicron or pre-Omicron SARS-CoV-2 variants.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {6}, pages = {1284-1286}, doi = {10.1111/apa.16764}, pmid = {36938946}, issn = {1651-2227}, support = {65925795//Pfizer grant/ ; }, mesh = {Child ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36938772, year = {2023}, author = {Mooney, A}, title = {Introduction to the special section on myalgic encephalomyelitis/chronic fatigue syndrome and Long COVID.}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1175-1177}, doi = {10.3233/WOR-236013}, pmid = {36938772}, issn = {1875-9270}, mesh = {Humans ; *Fatigue Syndrome, Chronic/complications ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36938768, year = {2023}, author = {Davenport, TE and Stevens, SR and Stevens, J and Snell, CR and Van Ness, JM}, title = {Development and measurement properties of the PEM/PESE activity questionnaire (PAQ).}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1187-1197}, doi = {10.3233/WOR-220553}, pmid = {36938768}, issn = {1875-9270}, mesh = {Humans ; *Activities of Daily Living ; Reproducibility of Results ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Existing instruments often are inappropriate to measure the effects of post-exertional malaise (PEM) and post-exertional symptom exacerbation (PESE) on activities of daily living (ADLs). A validated questionnaire to measure self-reported ability with ADLs would advance research and clinical practice in conditions like myalgic encephalomyelitis and Long Covid.

OBJECTIVE: Determine the measurement properties of the PEM/PESE Activity Questionnaire (PAQ).

METHODS: The PAQ is adapted from the Patient Specific Functional Scale. Respondents rated three self-selected ADLs on two 0-100 scales, including current performance compared to (1) a 'good day' and (2) before illness. Respondents provided a Burden of Functioning rating on a 0-100 scale, anchored at 0 being the activity took "No time, effort, and resources at all" and 10 being "All of my time, effort, and resources." Respondents took the PAQ twice, completing a demographic questionnaire after the first PAQ and before the second PAQ. Descriptive statistics and intraclass correlation coefficients were calculated for each scale to assess test-retest reliability. Minimum detectable change outside the 95% confidence interval (MDC95) was calculated. Ceiling and floor effects were determined when the MDC95 for average and function scores crossed 0 and 100, respectively.

RESULTS: n = 981 responses were recorded, including n = 675 complete surveys. Test-retest reliability was generally fair to excellent, depending on function and scale. MDC95 values generally indicated scale responsiveness. Ceiling and floor effects were noted infrequently for specific functions.

CONCLUSION: The PAQ is valid, reliable, and sensitive. Additional research may explore measurement properties involving functions that were infrequently selected in this sample.}, } @article {pmid36937672, year = {2023}, author = {Thapaliya, K and Marshall-Gradisnik, S and Barth, M and Eaton-Fitch, N and Barnden, L}, title = {Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1125208}, pmid = {36937672}, issn = {1662-4548}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla. Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with "pain" and negative correlations between the midbrain and whole brainstem volumes with "breathing difficulty." In long COVID patients a strong negative relationship was detected between midbrain volume and "breathing difficulty." Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.}, } @article {pmid36937488, year = {2023}, author = {Stoian, M and Procopiescu, B and Șeitan, S and Scarlat, G}, title = {Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder.}, journal = {Journal of medicine and life}, volume = {16}, number = {2}, pages = {195-202}, pmid = {36937488}, issn = {1844-3117}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Risk Factors ; }, abstract = {Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.}, } @article {pmid36936993, year = {2023}, author = {López-Hernández, Y and Oropeza-Valdez, JJ and García Lopez, DA and Borrego, JC and Murgu, M and Valdez, J and López, JA and Monárrez-Espino, J}, title = {Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1100486}, pmid = {36936993}, issn = {2296-889X}, abstract = {Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.}, } @article {pmid36936802, year = {2023}, author = {Sadiq, AM and Hassanali, ZR and Nziku, EB and Sadiq, AM and Dekker, MCJ}, title = {Long COVID? Fatal case report of ischemic stroke and pulmonary embolism post COVID-19 infection.}, journal = {Radiology case reports}, volume = {18}, number = {5}, pages = {1913-1917}, pmid = {36936802}, issn = {1930-0433}, abstract = {Coronavirus disease 19 (COVID-19) may lead to post-COVID syndrome a few weeks to months after the infection with various symptoms. Post-COVID thromboembolic syndrome may be a result of coagulopathy that occurs in both the arterial and venous circulation. Apart from direct cellular infection, post-COVID syndrome may occur due to immune system dysregulation, endothelial injury, and hypercoagulability, leading to thrombosis. We present a 32-year-old man who was diagnosed with mild symptoms of COVID-19 infection 4 months before an acute ischemic stroke and an asymptomatic pulmonary embolism. A COVID-19 antigen test was negative. An analysis of prothrombotic factors was negative. He could not receive any therapeutic intervention before his demise. The extent of COVID-19 infection after the onset of symptoms is a mystery and poses a fatal concern due to the increasing number of complications. The long-term complications after COVID-19 infection are still not understood. Clinicians need to be aware of any signs and symptoms that may arise months after COVID-19 infection and its possible causal relationship.}, } @article {pmid36936586, year = {2022}, author = {O'Mahoney, L and Khunti, K}, title = {Long covid: risk factors, outcomes, and future directions for research.}, journal = {BMJ medicine}, volume = {1}, number = {1}, pages = {e000257}, pmid = {36936586}, issn = {2754-0413}, } @article {pmid36936404, year = {2023}, author = {McAuley, HJC and Evans, RA and Bolton, CE and Brightling, CE and Chalmers, JD and Docherty, AB and Elneima, O and Greenhaff, PL and Gupta, A and Harris, VC and Harrison, EM and Ho, LP and Horsley, A and Houchen-Wolloff, L and Jolley, CJ and Leavy, OC and Lone, NI and Man, WD and Marks, M and Parekh, D and Poinasamy, K and Quint, JK and Raman, B and Richardson, M and Saunders, RM and Sereno, M and Shikotra, A and Singapuri, A and Singh, SJ and Steiner, M and Tan, AL and Wain, LV and Welch, C and Whitney, J and Witham, MD and Lord, J and Greening, NJ and , }, title = {Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.}, journal = {EClinicalMedicine}, volume = {57}, number = {}, pages = {101896}, pmid = {36936404}, issn = {2589-5370}, support = {209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_00008/5/MRC_/Medical Research Council/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20002/MRC_/Medical Research Council/United Kingdom ; MC_UU_00036/2/MRC_/Medical Research Council/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; }, abstract = {BACKGROUND: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty.

METHODS: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107.

FINDINGS: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered.

INTERPRETATION: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required.

FUNDING: UK Research and Innovation and National Institute for Health Research.}, } @article {pmid36936268, year = {2023}, author = {Byambasuren, O and Stehlik, P and Clark, J and Alcorn, K and Glasziou, P}, title = {Effect of covid-19 vaccination on long covid: systematic review.}, journal = {BMJ medicine}, volume = {2}, number = {1}, pages = {e000385}, pmid = {36936268}, issn = {2754-0413}, abstract = {OBJECTIVE: To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and symptoms of long covid.

DESIGN: Systematic review.

DATA SOURCES: PubMed, Embase, and Cochrane covid-19 trials, and Europe PubMed Central (Europe PMC) for preprints, from 1 January 2020 to 3 August 2022.

Trials, cohort studies, and case-control studies reporting on patients with long covid and symptoms of long covid, with vaccination before and after infection with the SARS-CoV-2 virus, or after a diagnosis of long covid. Risk of bias was assessed with the ROBINS-I tool.

RESULTS: 1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.

CONCLUSIONS: Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.

PROTOCOL REGISTRATION: Open Science Framework https://osf.io/e8jdy.}, } @article {pmid36936263, year = {2023}, author = {Edwards, F and Hamilton, FW}, title = {Impact of covid-19 vaccination on long covid.}, journal = {BMJ medicine}, volume = {2}, number = {1}, pages = {e000470}, pmid = {36936263}, issn = {2754-0413}, } @article {pmid36932242, year = {2023}, author = {Routen, A and O'Mahoney, L and Aiyegbusi, OL and Alder, Y and Banerjee, A and Buckland, L and Brightling, C and Calvert, M and Camaradou, J and Chaturvedi, N and Chong, A and Dalrymple, E and Eggo, RM and Elliott, P and Evans, RA and Gibson, A and Haroon, S and Herrett, E and Houchen-Wolloff, L and Hughes, SE and Jeyes, F and Matthews, K and McMullan, C and Morley, J and Shafran, R and Smith, N and Stanton, D and Stephenson, T and Sterne, J and Turner, GM and Ward, H and Khunti, K}, title = {Patient and public involvement within epidemiological studies of long COVID in the UK.}, journal = {Nature medicine}, volume = {29}, number = {4}, pages = {771-773}, pmid = {36932242}, issn = {1546-170X}, support = {MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_20049/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Epidemiologic Studies ; United Kingdom/epidemiology ; }, } @article {pmid36931142, year = {2023}, author = {Zheng, YB and Zeng, N and Yuan, K and Tian, SS and Yang, YB and Gao, N and Chen, X and Zhang, AY and Kondratiuk, AL and Shi, PP and Zhang, F and Sun, J and Yue, JL and Lin, X and Shi, L and Lalvani, A and Shi, J and Bao, YP and Lu, L}, title = {Prevalence and risk factor for long COVID in children and adolescents: A meta-analysis and systematic review.}, journal = {Journal of infection and public health}, volume = {16}, number = {5}, pages = {660-672}, pmid = {36931142}, issn = {1876-035X}, mesh = {Prevalence ; Adolescent ; Systemic Inflammatory Response Syndrome ; Child ; Risk Factors ; Female ; *COVID-19/epidemiology/complications ; Humans ; Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Millions of COVID-19 pediatric survivors are facing the risk of long COVID after recovery from acute COVID-19. The primary objective of this study was to systematically review the available literature and determine the pooled prevalence of, and risk factors for long COVID among the pediatric survivors.

METHODS: Studies that assessed the prevalence of, or risk factors associated with long COVID among pediatric COVID-19 survivors were systematically searched in PubMed, Embase, and Cochrane Library up to December 11th, 2022. Random effects model was performed to estimate the pooled prevalence of long COVID among pediatric COVID-19 patients. Subgroup analyses and meta-regression on the estimated prevalence of long COVID were performed by stratification with follow-up duration, mean age, sex ratio, percentage of multisystem inflammatory syndrome, hospitalization rate at baseline, and percentage of severe illness.

RESULTS: Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % ([95 % CI 15.27-32.53]). The generalized symptom (19.57 %, [95 % CI 9.85-31.52]) was reported most commonly, followed by respiratory (14.76 %, [95 % CI 7.22-24.27]), neurologic (13.51 %, [95 % CI 6.52-22.40]), and psychiatric (12.30 %, [95% CI 5.38-21.37]). Dyspnea (22.75 %, [95% CI 9.38-39.54]), fatigue (20.22 %, [95% CI 9.19-34.09]), and headache (15.88 %, [95 % CI 6.85-27.57]) were most widely reported specific symptoms. The prevalence of any symptom during 3-6, 6-12, and> 12 months were 26.41 % ([95 % CI 14.33-40.59]), 20.64 % ([95 % CI 17.06-24.46]), and 14.89 % ([95 % CI 6.09-26.51]), respectively. Individuals with aged over ten years, multisystem inflammatory syndrome, or had severe clinical symptoms exhibited higher prevalence of long COVID in multi-systems. Factors such as older age, female, poor physical or mental health, or had severe infection or more symptoms were more likely to have long COVID in pediatric survivors.

CONCLUSIONS: Nearly one quarter of pediatric survivors suffered multisystem long COVID, even at 1 year after infection. Ongoing monitoring, comprehensive prevention and intervention is warranted for pediatric survivors, especially for individuals with high risk factors.}, } @article {pmid36928222, year = {2023}, author = {Asakawa, T and Cai, Q and Shen, J and Zhang, Y and Li, Y and Chen, P and Luo, W and Zhang, J and Zhou, J and Zeng, H and Weng, R and Hu, F and Feng, H and Chen, J and Huang, J and Zhang, X and Zhao, Y and Fang, L and Yang, R and Huang, J and Wang, F and Liu, Y and Lu, H}, title = {Sequelae of long COVID, known and unknown: A review of updated information.}, journal = {Bioscience trends}, volume = {17}, number = {2}, pages = {85-116}, doi = {10.5582/bst.2023.01039}, pmid = {36928222}, issn = {1881-7823}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Public Health ; }, abstract = {Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.}, } @article {pmid36926600, year = {2023}, author = {Lorman, V and Rao, S and Jhaveri, R and Case, A and Mejias, A and Pajor, NM and Patel, P and Thacker, D and Bose-Brill, S and Block, J and Hanley, PC and Prahalad, P and Chen, Y and Forrest, CB and Bailey, LC and Lee, GM and Razzaghi, H}, title = {Understanding pediatric long COVID using a tree-based scan statistic approach: an EHR-based cohort study from the RECOVER Program.}, journal = {JAMIA open}, volume = {6}, number = {1}, pages = {ooad016}, pmid = {36926600}, issn = {2574-2531}, abstract = {OBJECTIVES: Post-acute sequalae of SARS-CoV-2 infection (PASC) is not well defined in pediatrics given its heterogeneity of presentation and severity in this population. The aim of this study is to use novel methods that rely on data mining approaches rather than clinical experience to detect conditions and symptoms associated with pediatric PASC.

MATERIALS AND METHODS: We used a propensity-matched cohort design comparing children identified using the new PASC ICD10CM diagnosis code (U09.9) (N = 1309) to children with (N = 6545) and without (N = 6545) SARS-CoV-2 infection. We used a tree-based scan statistic to identify potential condition clusters co-occurring more frequently in cases than controls.

RESULTS: We found significant enrichment among children with PASC in cardiac, respiratory, neurologic, psychological, endocrine, gastrointestinal, and musculoskeletal systems, the most significant related to circulatory and respiratory such as dyspnea, difficulty breathing, and fatigue and malaise.

DISCUSSION: Our study addresses methodological limitations of prior studies that rely on prespecified clusters of potential PASC-associated diagnoses driven by clinician experience. Future studies are needed to identify patterns of diagnoses and their associations to derive clinical phenotypes.

CONCLUSION: We identified multiple conditions and body systems associated with pediatric PASC. Because we rely on a data-driven approach, several new or under-reported conditions and symptoms were detected that warrant further investigation.}, } @article {pmid36924785, year = {2023}, author = {Boyton, RJ and Altmann, DM}, title = {Imprinted hybrid immunity against XBB reinfection.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {7}, pages = {764-765}, pmid = {36924785}, issn = {1474-4457}, support = {MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Reinfection ; *Adaptive Immunity ; }, } @article {pmid36922471, year = {2023}, author = {Sah, RR and Dash, N and Kumar, S and Dawman, L and Verma, S}, title = {Long COVID in Children up to 12 y of Age - A Retrospective Telephonic Survey.}, journal = {Indian journal of pediatrics}, volume = {90}, number = {6}, pages = {627}, pmid = {36922471}, issn = {0973-7693}, mesh = {Humans ; Child ; Retrospective Studies ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36922030, year = {2023}, author = {Scott, NA and Pearmain, L and Knight, SB and Brand, O and Morgan, DJ and Jagger, C and Harbach, S and Khan, S and Shuwa, HA and Franklin, M and Kästele, V and Williams, T and Prise, I and McClure, FA and Hackney, P and Smith, L and Menon, M and Konkel, JE and Lawless, C and Wilson, J and Mathioudakis, AG and Stanel, SC and Ustianowski, A and Lindergard, G and Brij, S and Diar Bakerly, N and Dark, P and Brightling, C and Rivera-Ortega, P and Lord, GM and Horsley, A and , and Piper Hanley, K and Felton, T and Simpson, A and Grainger, JR and Hussell, T and Mann, ER}, title = {Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.}, journal = {The European respiratory journal}, volume = {61}, number = {5}, pages = {}, pmid = {36922030}, issn = {1399-3003}, support = {202865/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MR/L011840/1/MRC_/Medical Research Council/United Kingdom ; MR/P023541/1/MRC_/Medical Research Council/United Kingdom ; MR/R00191X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Monocytes/metabolism ; Chemokines, CXC/metabolism ; Receptors, Virus/metabolism ; Receptors, CXCR6 ; Receptors, Chemokine/metabolism ; Post-Acute COVID-19 Syndrome ; *Lung Injury ; Ligands ; Convalescence ; *Influenza, Human ; Receptors, Scavenger/metabolism ; *COVID-19 ; Chemokine CXCL16 ; Patient Acuity ; }, abstract = {BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).

METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury.

RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence.

CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.}, } @article {pmid36921943, year = {2023}, author = {Zahouani, I and Desmeules, F and Perreault, K and Campeau-Lecours, A and Best, K and Beaulieu-Bonneau, S and Paquette, JS and Deslauriers, S and Daigle, N and Drouin, G and Tittley, J and Gagnon, MA and Salmam, I and Brouillard, SM and Lepage, K and Roy, JS}, title = {Physical and cognitive impairments in people suffering from long COVID: protocol for a longitudinal population-based cohort study.}, journal = {BMJ open}, volume = {13}, number = {3}, pages = {e064054}, pmid = {36921943}, issn = {2044-6055}, support = {//CIHR/Canada ; }, mesh = {Adult ; Humans ; *Cognitive Dysfunction/epidemiology ; Cohort Studies ; *COVID-19/epidemiology ; Gait ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {INTRODUCTION: Approximately 33% of people who contracted COVID-19 still experience symptoms 12 weeks after infection onset. This persistence of symptoms is now considered a syndrome itself called 'long COVID'. Evidence regarding long COVID and its cognitive and physical impacts is growing, but the literature is currently lacking objectively measured data to guide towards adapted healthcare trajectories. The objectives are to describe the physical and cognitive impairments experienced by individuals living with long COVID using self-reported and clinical objective measures, and to compare the evolution over time of the physical and cognitive state between adults living with long COVID (at least one physical or cognitive COVID-19 symptom for more than 12 weeks following infection; long COVID group), people who developed COVID-19 but did not experience persistent symptoms (short COVID group) and people who did not develop COVID-19 (control group).

METHODS AND ANALYSIS: In this longitudinal cohort study, 120 participants will be recruited in each group. Variables will be collected through three evaluation sessions over 6 months (baseline, 3 months, 6 months). Variables include self-administered questionnaires on health-related quality of life, comorbidity, sleep, pain, anxiety, depressive symptoms, fatigue and cognitive function, as well as objective measures of cognitive (attention, memory, executive functioning) and physical (grip strength, balance, gait speed, gait endurance, VO2, frailty) functions. Activity, heart rate and sleep will be monitored with a fitness tracker watch for 7 days following evaluation sessions. Maximum-likelihood analyses of variance (ANOVAs) will be used to compare data at baseline between groups. Repeated measures ANOVAs will be used to compare the longitudinal performance variations across groups of the self-reported and clinical variables.

ETHICS AND DISSEMINATION: Ethics committees of the CIUSSS de la Capitale-Nationale and CIUSSS de l'Est-de-l'Île-de-Montréal approved the project. Results will be disseminated through clinical and community platforms as well as through peer-reviewed manuscripts and international conferences.

TRIAL REGISTRATION NUMBER: NCT05216536.}, } @article {pmid36921564, year = {2023}, author = {Qi, E and Courcoubetis, G and Liljegren, E and Herrera, E and Nguyen, N and Nadri, M and Ghandehari, S and Kazemian, E and Reckamp, KL and Merin, NM and Merchant, A and Mason, J and Figueiredo, JC and Shishido, SN and Kuhn, P}, title = {Investigation of liquid biopsy analytes in peripheral blood of individuals after SARS-CoV-2 infection.}, journal = {EBioMedicine}, volume = {90}, number = {}, pages = {104519}, pmid = {36921564}, issn = {2352-3964}, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS) is linked to severe organ damage. The identification and stratification of at-risk SARS-CoV-2 infected individuals is vital to providing appropriate care. This exploratory study looks for a potential liquid biopsy signal for PACS using both manual and machine learning approaches.

METHODS: Using a high definition single cell assay (HDSCA) workflow for liquid biopsy, we analysed 100 Post-COVID patients and 19 pre-pandemic normal donor (ND) controls. Within our patient cohort, 73 had received at least 1 dose of vaccination prior to SARS-CoV-2 infection. We stratified the COVID patients into 25 asymptomatic, 22 symptomatic COVID-19 but not suspected for PACS and 53 PACS suspected. All COVID-19 patients investigated in this study were diagnosed between April 2020 and January 2022 with a median 243 days (range 16-669) from diagnosis to their blood draw. We did a histopathological examination of rare events in the peripheral blood and used a machine learning model to evaluate predictors of PACS.

FINDINGS: The manual classification found rare cellular and acellular events consistent with features of endothelial cells and platelet structures in the PACS-suspected cohort. The three categories encompassing the hypothesised events were observed at a significantly higher incidence in the PACS-suspected cohort compared to the ND (p-value < 0.05). The machine learning classifier performed well when separating the NDs from Post-COVID with an accuracy of 90.1%, but poorly when separating the patients suspected and not suspected of PACS with an accuracy of 58.7%.

INTERPRETATION: Both the manual and the machine learning model found differences in the Post-COVID cohort and the NDs, suggesting the existence of a liquid biopsy signal after active SARS-CoV-2 infection. More research is needed to stratify PACS and its subsyndromes.

FUNDING: This work was funded in whole or in part by Fulgent Genetics, Kathy and Richard Leventhal and Vassiliadis Research Fund. This work was also supported by the National Cancer InstituteU54CA260591.}, } @article {pmid36920842, year = {2023}, author = {Nair, CV and Moni, M and Edathadathil, F and A, A and Prasanna, P and Pushpa Raghavan, R and Sathyapalan, DT and Jayant, A}, title = {Incidence and Characterization of Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors to Recognize Syndemic Connotations in India: Single-Center Prospective Observational Cohort Study.}, journal = {JMIR formative research}, volume = {7}, number = {}, pages = {e40028}, pmid = {36920842}, issn = {2561-326X}, abstract = {BACKGROUND: Long COVID, or post-COVID-19 syndrome, is the persistence of signs and symptoms that develop during or after COVID-19 infection for more than 12 weeks and are not explained by an alternative diagnosis. In spite of health care recouping to prepandemic states, the post-COVID-19 state tends to be less recognized from low- and middle-income country settings and holistic therapeutic protocols do not exist. Owing to the syndemic nature of COVID-19, it is important to characterize post-COVID-19 syndrome.

OBJECTIVE: We aimed to determine the incidence of post-COVID-19 symptoms in a cohort of inpatients who recovered from COVID-19 from February to July 2021 at a tertiary-care center in South India. In addition, we aimed at comparing the prevalence of post-COVID-19 manifestations in intensive care unit (ICU) and non-ICU patients, assessing the persistence, severity, and characteristics of post-COVID-19 manifestations, and elucidating the risk factors associated with the presence of post-COVID-19 manifestations.

METHODS: A total of 120 adult patients admitted with COVID-19 in the specified time frame were recruited into the study after providing informed written consent. The cohort included 50 patients requiring intensive care and 70 patients without intensive care. The follow-up was conducted on the second and sixth weeks after discharge with a structured questionnaire. The questionnaire was filled in by the patient/family member of the patient during their visit to the hospital for follow-up at 2 weeks and through telephone follow-up at 6 weeks.

RESULTS: The mean age of the cohort was 55 years and 55% were men. Only 5% of the cohort had taken the first dose of COVID-19 vaccination. Among the 120 patients, 58.3% had mild COVID-19 and 41.7% had moderate to severe COVID-19 infection. In addition, 60.8% (n=73) of patients had at least one persistent symptom at the sixth week of discharge and 50 (41.7%) patients required intensive care during their inpatient stay. The presence of persistent symptoms at 6 weeks was not associated with severity of illness, age, or requirement for intensive care. Fatigue was the most common reported persistent symptom with a prevalence of 55.8%, followed by dyspnea (20%) and weight loss (16.7%). Female sex (odds ratio [OR] 2.4, 95% CI 1.03-5.58; P=.04) and steroid administration during hospital stay (OR 4.43, 95% CI 1.9-10.28; P=.001) were found to be significant risk factors for the presence of post-COVID-19 symptoms at 6 weeks as revealed by logistic regression analysis.

CONCLUSIONS: Overall, 60.8% of inpatients treated for COVID-19 had post-COVID-19 symptoms at 6 weeks postdischarge from the hospital. The incidence of post-COVID-19 syndrome in the cohort did not significantly differ across the mild, moderate, and severe COVID-19 severity categories. Female sex and steroid administration during the hospital stay were identified as predictors of the persistence of post-COVID-19 symptoms at 6 weeks.}, } @article {pmid36920723, year = {2023}, author = {Schloss, JV}, title = {Nutritional deficiencies that may predispose to long COVID.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {573-583}, pmid = {36920723}, issn = {1568-5608}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; *Malnutrition/complications/epidemiology ; Zinc ; }, abstract = {Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.}, } @article {pmid36920416, year = {2023}, author = {Daly, E and Collins, G and Hall, E and O'Dwyer, J and Gallagher, D and Kelly, J}, title = {Telehealth Rehabilitation for the Management of Long Covid Symptoms.}, journal = {Irish medical journal}, volume = {115}, number = {No.9}, pages = {677}, pmid = {36920416}, issn = {0332-3102}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Telemedicine ; SARS-CoV-2 ; }, } @article {pmid36917827, year = {2023}, author = {Al-Hakeim, HK and Al-Rubaye, HT and Jubran, AS and Almulla, AF and Moustafa, SR and Maes, M}, title = {Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection.}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {45}, number = {3}, pages = {205-215}, pmid = {36917827}, issn = {1809-452X}, mesh = {Humans ; *Insulin Resistance/physiology ; Depression ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Blood Glucose/metabolism ; *COVID-19 ; Insulin ; }, abstract = {OBJECTIVE: Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases.

METHODS: This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute ß-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls.

RESULTS: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID.

CONCLUSION: Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.}, } @article {pmid36917411, year = {2023}, author = {Williams, LD and Zis, P}, title = {COVID-19-Related Burning Eye Syndrome and Burning Mouth Syndrome: A Systematic Review and Meta-analysis.}, journal = {Pain and therapy}, volume = {12}, number = {3}, pages = {621-630}, pmid = {36917411}, issn = {2193-8237}, abstract = {BACKGROUND: Previous research highlights burning eye syndrome (BES) and burning mouth syndrome (BMS) as chronic complications of COVID-19 infection. The aim of this systematic review and meta-analysis is to establish the prevalence of COVID-19-related BES and COVID-19-related BMS and describe their phenomenology.

METHODOLOGY: A literature search in the PubMed database was performed, and seven papers (five on BES and two on BMS) were eligible to be included in this systematic review and meta-analysis.

RESULTS: The pooled prevalence of COVID-19-related BES was 9.9% (95% CI 3.4-25.4%). The frequency of COVID-19-related BMS is only reported in isolated cases and ranges from 4% in mild-to-moderate cases to 15% in severe, hospitalized cases, with female patients being mostly affected. COVID-19 severity is a potential risk factor for both BES and BMS. Neither syndrome occurs in isolation. COVID-19-related BES usually appears within the first week post-infection, persisting up to 9 weeks later. COVID-19-related BMS occurs during and after initial infection, and may also persist as a chronic disease.

CONCLUSIONS: Both BES and BMS are neuropathic COVID-19 infection complications, still under-studied and under-investigated, despite the fact that both are prevalent. Both COVID-19-related BES and COVID-19-related BMS could potentially be initial long COVID syndrome manifestations, and further research should be carried out in this field.}, } @article {pmid36917277, year = {2023}, author = {Titus, AR and Mezuk, B and Hirschtick, JL and McKane, P and Elliott, MR and Fleischer, NL}, title = {Patterns and predictors of depressive and anxiety symptoms within a population-based sample of adults diagnosed with COVID-19 in Michigan.}, journal = {Social psychiatry and psychiatric epidemiology}, volume = {58}, number = {7}, pages = {1099-1108}, pmid = {36917277}, issn = {1433-9285}, support = {T32 HS026120/HS/AHRQ HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19 ; COVID-19 Testing ; Michigan ; Pandemics ; Anxiety ; Depression ; }, abstract = {PURPOSE: The COVID-19 pandemic has had wide-ranging impacts on mental health, however, less is known about predictors of mental health outcomes among adults who have experienced a COVID-19 diagnosis. We examined the intersection of demographic, economic, and illness-related predictors of depressive and anxiety symptoms within a population-based sample of adults diagnosed with COVID-19 in the U.S. state of Michigan early in the pandemic.

METHODS: Data were from a population-based survey of Michigan adults who experienced a COVID-19 diagnosis prior to August 1, 2020 (N = 1087). We used weighted prevalence estimates and multinomial logistic regression to examine associations between mental health outcomes (depressive symptoms, anxiety symptoms, and comorbid depressive/anxiety symptoms) and demographic characteristics, pandemic-associated changes in accessing basic needs (accessing food/clean water and paying important bills), self-reported COVID-19 symptom severity, and symptom duration.

RESULTS: Relative risks for experiencing poor mental health outcomes varied by sex, age, race/ethnicity, and income. In adjusted models, experiencing a change in accessing basic needs associated with the pandemic was associated with higher relative risks for anxiety and comorbid anxiety/depressive symptoms. Worse COVID-19 symptom severity was associated with a higher burden of comorbid depressive/anxiety symptoms. "Long COVID" (symptom duration greater than 60 days) was associated with all outcomes.

CONCLUSION: Adults diagnosed with COVID-19 may face overlapping risk factors for poor mental health outcomes, including pandemic-associated disruptions to household and economic wellbeing, as well as factors related to COVID-19 symptom severity and duration. An integrated approach to treating depressive/anxiety symptoms among COVID-19 survivors is warranted.}, } @article {pmid36916751, year = {2023}, author = {Sun, H and Zhou, J and Tang, LJ and Cao, WP and Li, YM}, title = {New challenges in the long-COVID syndrome.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {116}, number = {7}, pages = {608}, doi = {10.1093/qjmed/hcad041}, pmid = {36916751}, issn = {1460-2393}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36916685, year = {2023}, author = {Chalmers, S and Harrall, K and Wong, SY and Kablan, W and Clunie, G}, title = {A retrospective study of patients presenting with speech and language therapy needs within multidisciplinary Long COVID services: A service evaluation describing and comparing two cohorts across two NHS Trusts.}, journal = {International journal of language & communication disorders}, volume = {58}, number = {5}, pages = {1424-1439}, doi = {10.1111/1460-6984.12868}, pmid = {36916685}, issn = {1460-6984}, mesh = {Humans ; *Language Therapy ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; State Medicine ; Speech ; *COVID-19 ; Speech Therapy ; }, abstract = {BACKGROUND: Post-COVID Syndrome (also known as Long COVID) refers to the multi-system condition affecting individuals following COVID-19 infection. This can include speech and language therapy (SLT) needs, including voice, swallowing, communication and upper airway difficulties. There is limited published literature in this clinical area of practice, particularly for those receiving input from community SLT services.

AIMS: To describe and compare demand, typical SLT presentation and service delivery across two National Health Service (NHS) Long COVID multidisciplinary services. Independent retrospective service evaluation was completed for each service. Descriptive statistics were produced and compared across services. This service evaluation followed The Strengthening the Reporting of Observation Studies in Epidemiology guidelines for cohort studies.

OUTCOMES & RESULTS: The findings indicated similarities across the two services in SLT service need and demand, clinical presentations and intervention approaches provided within Long COVID services. There were specific differences in the service provision and delivery of intervention in cognitive communication and upper airways subspecialities.

This study highlights the clinical complexities of SLT needs in individuals with Long COVID and the importance for an appropriately skilled and supported workforce within effective multidisciplinary teams. We call for consensus on SLT practices and a consistent and standardized approach to evaluation for SLT needs in Long COVID.

WHAT THIS PAPER ADDS: What is already known on this subject SLT needs, including voice, swallowing, communication and upper airway difficulties, are present in individuals presenting with Long COVID, both in those who were or were not hospitalized. SLTs are seeing such individuals in a variety of settings, including community services and Long COVID multidisciplinary teams. There is minimal evidence of the clinical presentations and interventions provided to individuals with SLT needs compared across Long COVID services. What this study adds to existing knowledge This study compares two NHS Long COVID services providing a SLT service pathway. It highlights the similarities and differences in service demand and capacity, patient presentation, and SLT intervention to make suggestions for future practice consideration and priority evaluation. Expert consensus among SLT clinicians is a priority to ensure clinicians are delivering consistent and equitable care for patients, while new evidence and data emerge. A consistent and standardized approach to data collection and outcome measures is essential to ensure future research captures the impact and value of SLT input with individuals with Long COVID. What are the clinical implications of this work? The complexities and multifactorial SLT needs of individual with Long COVID call for appropriate SLT staffing provision, skill and training to fulfil the needs of this population. Speech and language therapists should be integrated with multidisciplinary Long COVID services to provide holistic care for patients and to support the professionals working with individuals with post-COVID voice, swallowing, communication and upper airway symptoms.}, } @article {pmid36915802, year = {2023}, author = {Lerum, TV and Meltzer, C and Rodriguez, JR and Aaløkken, TM and Brønstad, E and Aarli, BB and Aarberg-Lund, KM and Durheim, MT and Ashraf, H and Einvik, G and Skjønsberg, OH and Stavem, K}, title = {A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19.}, journal = {ERJ open research}, volume = {9}, number = {2}, pages = {}, pmid = {36915802}, issn = {2312-0541}, abstract = {COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while D LCO and total lung capacity improved (0.28 mmol·min[-1]·kPa[-1], 95% CI 0.12-0.44, and 0.13 L, 95% CI 0.02-0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, D LCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.}, } @article {pmid36915663, year = {2023}, author = {Wan, KS and Sundram, ER and Abdul Haddi, AA and Dashuki, AR and Ahad, A and John, R and Abdul Wahid, MR and Ungku Halmie, UIF and Ibrahim, FE and Abdul Rahim, NB}, title = {Long COVID active case detection initiative among COVID-19 patients in Port Dickson, Malaysia: a retrospective study on the positive outcomes, the proportion of patients with long COVID and its associated factors.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e14742}, pmid = {36915663}, issn = {2167-8359}, mesh = {Adult ; Female ; Humans ; Male ; *COVID-19/diagnosis ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Malaysia/epidemiology ; COVID-19 Testing ; Headache/diagnosis ; Myalgia/epidemiology ; }, abstract = {BACKGROUND: Long COVID is new or ongoing symptoms at four weeks or more after the start of acute COVID-19. However, the prevalence and factors associated with long COVID are largely unknown in Malaysia. We aim to determine the proportion and factors associated with long COVID among COVID-19 patients in Port Dickson, Malaysia. The positive outcomes of our long COVID active detection initiative were also described.

METHODS: This was a retrospective analysis of long COVID data collected by the Port Dickson District Health Office between 1 September 2021 to 31 October 2021. Monitoring long COVID symptoms was our quality improvement initiative to safeguard residents' health in the district. The study population was patients previously diagnosed with COVID-19 who resided in Port Dickson. The inclusion criteria were adults aged 18 years and above and were in the fifth week (day 29 to 35) post-COVID-19 diagnosis during the data collection period. We called all consecutive eligible patients to inquire regarding long COVID symptoms. Long COVID was defined as new or ongoing symptoms lasting more than 28 days from the date of positive SARS-CoV-2 by polymerase chain reaction test. Binary multivariate logistic regression was conducted to determine factors associated with long COVID.

RESULTS: Among 452 patients, they were predominantly male (54.2%), Malays (68.8%) and aged 18-29 years (58.6%). A total of 27.4% (95% CI [23.4-31.8]) of patients experienced long COVID symptoms and were referred to government clinics. The most frequent long COVID symptoms experienced were fatigue (54.0%), cough (20.2%), muscle pain (18.5%), headache (17.7%) and sleep disturbance (16.1%). Females, patients with underlying cardiovascular disease, asthma and chronic obstructive airway disease, those who received symptomatic care, and patients with myalgia and headaches at COVID-19 diagnosis were more likely to have long COVID. Three patients with suspected severe mental health problems were referred to the district psychologist, and ten patients with no/incomplete vaccination were referred for vaccination.

CONCLUSION: Long COVID is highly prevalent among COVID-19 patients in Port Dickson, Malaysia. Long-term surveillance and management of long COVID, especially among the high-risk groups, are needed as we transition to living with COVID-19.}, } @article {pmid36912409, year = {2023}, author = {Sarıoğlu, N and Aksu, GD and Çoban, H and Bülbül, E and Demirpolat, G and Arslan, AT and Erel, F}, title = {Clinical and radiological outcomes of longCOVID: Is the post-COVID fibrosis common?.}, journal = {Tuberkuloz ve toraks}, volume = {71}, number = {1}, pages = {48-57}, pmid = {36912409}, issn = {2980-3187}, mesh = {Humans ; Male ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Drug Treatment ; Quality of Life ; Lung ; Dyspnea ; Fibrosis ; }, abstract = {INTRODUCTION: COVID-19 survivors may take longer to regain full well-being. This study aimed to investigate clinical and functional evaluation and radiologic changes in the third month after COVID-19.

MATERIALS AND METHODS: A total of 126 patients were assessed in the third month for symptoms, pulmonary function, exercise capacity, radiologic imaging, and quality of life after being discharged following COVID-19 treatment. Two radiologists evaluated the initial and follow-up images.

RESULT: At the third month follow-up visit, the most common persisting symptoms were shortness of breath (32.5%), cough (12.7%), and muscle pain (12.7%). At the follow-up visit, oxygen saturations at rest and after a sixmin walking test were lower in patients with prior intensive care hospitalization compared to those without (p<0.001, p= 0.004). Computed tomography (CT) scans revealed persisting pulmonary pathologies in 64.6% of patients at the third month follow-up. The most common pathologies on follow-up thoracic CT were fibrotic-like changes in 44.2% and ground-glass opacities (GGO) in 33.3%. Regression analysis unveiled that age [95% confidence interval (CI), 1.01 to 1.15; p= 0.020], male sex (95% CI, 4.06 to 95.3, p<0.001), first CT severity score (95% CI, 1.02 to 1.41, p= 0.028), duration of hospitalization (95% CI, 1.02 to 1.18, p= 0.012), oxygen saturation (95% CI, 0.86 to 0.96, p<0.001) were independent predictors of fibrotic-like changes.

CONCLUSIONS: In the third month following COVID-19, the most common symptom was dyspnea, and the most common radiological findings were fibrotic-like changes and GGO. Longer follow-up studies of COVID-19 survivors are needed to observe lasting changes.}, } @article {pmid36911963, year = {2023}, author = {Vernon, SD and Hartle, M and Sullivan, K and Bell, J and Abbaszadeh, S and Unutmaz, D and Bateman, L}, title = {Post-exertional malaise among people with long COVID compared to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1179-1186}, doi = {10.3233/WOR-220581}, pmid = {36911963}, issn = {1875-9270}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Long COVID describes a condition with symptoms that linger for months to years following acute COVID-19. Many of these Long COVID symptoms are like those experienced by patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

OBJECTIVE: We wanted to determine if people with Long COVID experienced post-exertional malaise (PEM), the hallmark symptom of ME/CFS, and if so, how it compared to PEM experienced by patients with ME/CFS.

METHODS: A questionnaire that asked about the domains of PEM including triggers, experience, recovery, and prevention was administered to 80 people seeking care for Long COVID at Bateman Horne Center. Their responses were compared to responses about PEM given by 151 patients with ME/CFS using chi-square tests of independence.

RESULTS: All but one Long COVID respondent reported having PEM. There were many significant differences in the types of PEM triggers, symptoms experienced during PEM, and ways to recover and prevent PEM between Long COVID and ME/CFS. Similarities between Long COVID and ME/CFS included low and medium physical and cognitive exertion to trigger PEM, symptoms of fatigue, pain, immune reaction, neurologic, orthostatic intolerance, and gastrointestinal symptoms during PEM, rest to recover from PEM, and pacing to prevent PEM.

CONCLUSION: People with Long COVID experience PEM. There were significant differences in PEM experienced by people with Long COVID compared to patients with ME/CFS. This may be due to the newness of Long COVID, not knowing what exertional intolerance is or how to manage it.}, } @article {pmid36911962, year = {2023}, author = {Tuller, D and Vink, M}, title = {Graded exercise therapy and cognitive behavior therapy do not improve employment outcomes in ME/CFS.}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1235-1239}, doi = {10.3233/WOR-220569}, pmid = {36911962}, issn = {1875-9270}, mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology ; Exercise Therapy ; Employment ; *Cognitive Behavioral Therapy ; }, } @article {pmid36911961, year = {2023}, author = {Sirotiak, Z}, title = {My experience with ME/CFS and implications: A personal narrative.}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1253-1259}, doi = {10.3233/WOR-220487}, pmid = {36911961}, issn = {1875-9270}, mesh = {Female ; Humans ; *Fatigue Syndrome, Chronic/complications/therapy/diagnosis ; *COVID-19 ; }, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating health condition characterized by overwhelming fatigue and post-exertional malaise, or exacerbation of symptoms following physical, mental, or emotional exertion. ME/CFS often impacts every aspect of an individual's life, and one's new reality may be much different from the daily life experienced before the onset of the condition. Though the long-term effects of COVID-19 have brought increased attention to chronic fatigue and related disorders, ME/CFS is still vastly understudied and frequently misunderstood. People with ME/CFS are often passed between various healthcare providers as evidence-based treatments remain scarce. These patients are sometimes sent to rehabilitation professionals, who often lack appropriate education and experience with this patient population. This article describes the experience of a young woman and physical therapist with ME/CFS following COVID-19 infection, as well as potential implications for rehabilitation professionals and those who care for those with this condition.}, } @article {pmid36911958, year = {2023}, author = {Jason, LA and Dorri, JA}, title = {Predictors of impaired functioning among long COVID patients.}, journal = {Work (Reading, Mass.)}, volume = {74}, number = {4}, pages = {1215-1224}, doi = {10.3233/WOR-220428}, pmid = {36911958}, issn = {1875-9270}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Pandemics ; *Cognitive Dysfunction ; Factor Analysis, Statistical ; }, abstract = {BACKGROUND: There is limited information on which acute factors predict more long-term symptoms from COVID-19.

OBJECTIVE: Our objective was to conduct an exploratory factor analysis of self-reported symptoms at two time points of Long COVID-19.

METHODS: Data from patients with Long COVID-19 were collected at the initial two weeks of contracting SARS CoV-2 and the most recent two weeks, with a mean duration of 21.7 weeks between the two-time points. At time point 2, participants also completed the Coronavirus Impact Scale (CIS), measuring how the COVID-19 pandemic affected various dimensions of their lives (e.g., routine, access to medical care, social/family support, etc.).

RESULTS: At time 1, a three-factor model emerged consisting of Cognitive Dysfunction, Autonomic Dysfunction and Gastrointestinal Dysfunction. The analysis of time 2 resulted in a three-factor model consisting of Cognitive Dysfunction, Autonomic Dysfunction, and Post-Exertional Malaise. Using factor scores from time 1, the Autonomic Dysfunction and the Gastrointestinal Dysfunction factor scores significantly predicted the CIS summary score at time two. In addition, the same two factor scores at time 1 predicted the occurrence of myalgic encephalomyelitis/chronic fatigue syndrome at time 2.

CONCLUSION: Cognitive and Autonomic Dysfunction emerged as factors for both time points. These results suggest that healthcare workers might want to pay particular attention to these factors, as they might be related to later symptoms and difficulties with returning to pre-illness family life and work functioning.}, } @article {pmid36910458, year = {2023}, author = {Tran, VT and Perrodeau, E and Saldanha, J and Pane, I and Ravaud, P}, title = {Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort.}, journal = {BMJ medicine}, volume = {2}, number = {1}, pages = {e000229}, pmid = {36910458}, issn = {2754-0413}, abstract = {OBJECTIVE: To evaluate the effect of covid-19 vaccination on the severity of symptoms in patients with long covid.

DESIGN: Target trial emulation based on ComPaRe e-cohort.

DATA SOURCE: ComPaRe long covid cohort, a nationwide e-cohort (ie, a cohort where recruitment and follow-up are performed online) of patients with long covid, in France.

METHODS: Adult patients (aged ≥18 years) enrolled in the ComPaRe cohort before 1 May 2021 were included in the study if they reported a confirmed or suspected SARS-CoV-2 infection, symptoms persistent for >3 weeks after onset, and at least one symptom attributable to long covid at baseline. Patients who received a first covid-19 vaccine injection were matched with an unvaccinated control group in a 1:1 ratio according to their propensity scores. Number of long covid symptoms, rate of complete remission of long covid, and proportion of patients reporting an unacceptable symptom state at 120 days were recorded.

RESULTS: 910 patients were included in the analyses (455 in the vaccinated group and 455 in the control group). By 120 days, vaccination had reduced the number of long covid symptoms (mean 13.0 (standard deviation 9.4) in the vaccinated group v 14.8 (9.8) in the control group; mean difference -1.8, 95% confidence interval -3.0 to -0.5) and doubled the rate of patients in remission (16.6% v 7.5%, hazard ratio 1.93, 95% confidence interval 1.18 to 3.14). Vaccination reduced the effect of long covid on patients' lives (mean score on the impact tool 24.3 (standard deviation 16.7) v 27.6 (16.7); mean difference -3.3, 95% confidence interval -5.7 to -1.0) and the proportion of patients with an unacceptable symptom state (38.9% v 46.4%, risk difference -7.4%, 95% confidence interval -14.5% to -0.3%). In the vaccinated group, two (0.4%) patients reported serious adverse events requiring admission to hospital.

CONCLUSION: In this study, covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients' social, professional, and family lives at 120 days in those with persistent symptoms of infection.}, } @article {pmid36909731, year = {2023}, author = {Varona, JF and Landete, P and Paredes, R and Vates, R and Torralba, M and Guisado-Vasco, P and Porras, L and Muñoz, P and Gijon, P and Ancochea, J and Saiz, E and Meira, F and Jimeno, JM and Lopez-Martin, JA and Estrada, V}, title = {Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1097809}, pmid = {36909731}, issn = {2235-2988}, mesh = {Humans ; Adult ; *COVID-19 ; Follow-Up Studies ; SARS-CoV-2 ; Hospitals ; Treatment Outcome ; }, abstract = {INTRODUCTION: The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized.

METHODS: Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.8 months [range, 15.2-19.5 months]). All patients were functionally autonomous with regard to daily living (Barthel index: 100) and had normal physical examinations.

RESULTS: From the APLICOV-PC date of discharge to the date of the extension visit, neither Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade 3-4 complications nor QT prolongation or significant electrocardiogram (EKG) abnormalities were reported. Five (14.7%) patients had another COVID-19 episode after initial discharge from APLICOV-PC, and in 2 patients (5.9%), previously unreported chest X-ray findings were documented. Spirometry and lung-diffusion tests were normal in 29 (85.3%) and 27 (79.4%) patients, respectively, and 3 patients needed additional oxygen supplementation after initial hospital discharge. None of these patients required subsequent hospital readmission for disease-related complications.

DISCUSSION: In conclusion, plitidepsin has demonstrated a favorable long-term safety profile in adult patients hospitalized for COVID-19. With the constraints of a low sample size and a lack of control, the rate of post-COVID-19 complications after treatment with plitidepsin is in the low range of published reports. (ClinicalTrials.gov Identifier: NCT05121740; https://clinicaltrials.gov/ct2/show/NCT05121740).}, } @article {pmid36908615, year = {2023}, author = {Bonilla, H and Quach, TC and Tiwari, A and Bonilla, AE and Miglis, M and Yang, PC and Eggert, LE and Sharifi, H and Horomanski, A and Subramanian, A and Smirnoff, L and Simpson, N and Halawi, H and Sum-Ping, O and Kalinowski, A and Patel, ZM and Shafer, RW and Geng, LN}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic.}, journal = {Frontiers in neurology}, volume = {14}, number = {}, pages = {1090747}, pmid = {36908615}, issn = {1664-2295}, abstract = {BACKGROUND: The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined.

METHODS: We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) phenotype.

FINDINGS: The median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS, majority were female, and obesity (BMI > 30 Kg/m[2]) (P = 0.00377895) and worse functional status (P = 0.0110474) were significantly associated with ME/CFS.

INTERPRETATIONS: Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.}, } @article {pmid36908059, year = {2023}, author = {Kleebayoon, A and Wiwanitkit, V}, title = {Long-COVID-19 patients and sleep disorders: correspondence.}, journal = {The Libyan journal of medicine}, volume = {18}, number = {1}, pages = {2188653}, pmid = {36908059}, issn = {1819-6357}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Sleep Wake Disorders ; }, } @article {pmid36906677, year = {2023}, author = {Griffith, LE and Beauchamp, M and McMillan, J and Borhan, S and Oz, UE and Wolfson, C and Kirkland, S and Basta, NE and Thompson, M and Raina, P and , }, title = {Persistent COVID-19 symptoms in community-living older adults from the Canadian Longitudinal Study on Aging (CLSA).}, journal = {Communications medicine}, volume = {3}, number = {1}, pages = {36}, pmid = {36906677}, issn = {2730-664X}, support = {NA//Public Health Agency of Canada (Agence de la Santé Publique du Canada)/ ; }, abstract = {BACKGROUND: Symptom persistence in non-hospitalized COVID-19 patients, also known as Long COVID or Post-acute Sequelae of COVID-19, is not well characterized or understood, and few studies have included non-COVID-19 control groups.

METHODS: We used data from a cross-sectional COVID-19 questionnaire (September-December 2020) linked to baseline (2011-2015) and follow-up (2015-2018) data from a population-based cohort including 23,757 adults 50+ years to examine how age, sex, and pre-pandemic physical, psychological, social, and functional health were related to the severity and persistence of 23 COVID-19-related symptoms experienced between March 2020 and questionnaire completion.

RESULTS: The most common symptoms are fatigue, dry cough, muscle/joint pain, sore throat, headache, and runny nose; reported by over 25% of participant who had (n = 121) or did not have (n = 23,636) COVID-19 during the study period. The cumulative incidence of moderate/severe symptoms in people with COVID-19 is more than double that reported by people without COVID-19, with the absolute difference ranging from 16.8% (runny nose) to 37.8% (fatigue). Approximately 60% of male and 73% of female participants with COVID-19 report at least one symptom persisting >1 month. Persistence >1 month is higher in females (aIRR = 1.68; 95% CI: 1.03, 2.73) and those with multimorbidity (aIRR = 1.90; 95% CI: 1.02, 3.49); persistence >3 months decreases by 15% with each unit increase in subjective social status after adjusting for age, sex and multimorbidity.

CONCLUSIONS: Many people living in the community who were not hospitalized for COVID-19 still experience symptoms 1- and 3-months post infection. These data suggest that additional supports, for example access to rehabilitative care, are needed to help some individuals fully recover.}, } @article {pmid36906338, year = {2023}, author = {The Lancet, }, title = {Long COVID: 3 years in.}, journal = {Lancet (London, England)}, volume = {401}, number = {10379}, pages = {795}, doi = {10.1016/S0140-6736(23)00493-2}, pmid = {36906338}, issn = {1474-547X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36905145, year = {2023}, author = {Kahlert, CR and Strahm, C and Güsewell, S and Cusini, A and Brucher, A and Goppel, S and Möller, E and Möller, JC and Ortner, M and Ruetti, M and Stocker, R and Vuichard-Gysin, D and Besold, U and McGeer, A and Risch, L and Friedl, A and Schlegel, M and Vernazza, P and Kuster, SP and Kohler, P and , }, title = {Post-Acute Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Viral Variant and Vaccination Status: A Multicenter Cross-Sectional Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {2}, pages = {194-202}, pmid = {36905145}, issn = {1537-6591}, mesh = {Female ; Humans ; Adult ; Male ; *COVID-19/complications ; SARS-CoV-2 ; Cross-Sectional Studies ; Prospective Studies ; Disease Progression ; Vaccination ; }, abstract = {BACKGROUND: Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC.

METHODS: We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status.

RESULTS: Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1-2 vaccinations (P = .028) and 0.49 with ≥3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08-3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10-3.46) were significantly associated with the outcome.

CONCLUSIONS: Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.}, } @article {pmid36904676, year = {2023}, author = {Adang, EAMC and Strous, MTA and van den Bergh, JP and Gach, D and van Kampen, VEM and van Zeeland, REP and Barten, DG and van Osch, FHM}, title = {Association of Heart Rate Variability with Pulmonary Function Impairment and Symptomatology Post-COVID-19 Hospitalization.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {5}, pages = {}, pmid = {36904676}, issn = {1424-8220}, support = {2022-1//VieCuri Corona Foundation and Regio Noord-Limburg/ ; }, mesh = {Humans ; Heart Rate ; *COVID-19 ; Hospitalization ; Patient Discharge ; Lung ; }, abstract = {The persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and the number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10 s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.}, } @article {pmid36904195, year = {2023}, author = {Menezes, DC and Lima, PDL and Lima, IC and Uesugi, JHE and Vasconcelos, PFDC and Quaresma, JAS and Falcão, LFM}, title = {Metabolic Profile of Patients with Long COVID: A Cross-Sectional Study.}, journal = {Nutrients}, volume = {15}, number = {5}, pages = {}, pmid = {36904195}, issn = {2072-6643}, support = {#006/2020//AMAZON FOUNDATION FOR RESEARCH SUPPORT/ ; #09/2021//SECRETARY OF SCIENCE, TECHNOLOGY, AND HIGHER, PROFESSIONAL AND TECH-NOLOGICAL EDUCATION/ ; INCT: 406360/2022-7//CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - Brazil/ ; Notice n° 13/2020//COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - Brazil/ ; }, mesh = {Humans ; Female ; Male ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cross-Sectional Studies ; Metabolome ; }, abstract = {A significant proportion of patients experience a wide range of symptoms following acute coronavirus disease 2019 (COVID-19). Laboratory analyses of long COVID have demonstrated imbalances in metabolic parameters, suggesting that it is one of the many outcomes induced by long COVID. Therefore, this study aimed to illustrate the clinical and laboratory markers related to the course of the disease in patients with long COVID. Participants were selected using a clinical care programme for long COVID in the Amazon region. Clinical and sociodemographic data and glycaemic, lipid, and inflammatory screening markers were collected, and cross-sectionally analysed between the long COVID-19 outcome groups. Of the 215 participants, most were female and not elderly, and 78 were hospitalised during the acute COVID-19 phase. The main long COVID symptoms reported were fatigue, dyspnoea, and muscle weakness. Our main findings show that abnormal metabolic profiles (such as high body mass index measurement and high triglyceride, glycated haemoglobin A1c, and ferritin levels) are more prevalent in worse long COVID presentations (such as previous hospitalisation and more long-term symptoms). This prevalence may suggest a propensity for patients with long COVID to present abnormalities in the markers involved in cardiometabolic health.}, } @article {pmid36902849, year = {2023}, author = {Matsuda, Y and Tokumasu, K and Otsuka, Y and Sunada, N and Honda, H and Sakurada, Y and Nakano, Y and Hasegawa, T and Obika, M and Ueda, K and Otsuka, F}, title = {Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902849}, issn = {2077-0383}, support = {2022//Ryobi Teien Memory Foundation in Japan/ ; }, abstract = {OBJECTIVES: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients.

METHODS: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia.

RESULTS: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue.

CONCLUSIONS: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.}, } @article {pmid36902702, year = {2023}, author = {Ranucci, M and Baryshnikova, E and Anguissola, M and Pugliese, S and Ranucci, L and Falco, M and Menicanti, L}, title = {The Very Long COVID: Persistence of Symptoms after 12-18 Months from the Onset of Infection and Hospitalization.}, journal = {Journal of clinical medicine}, volume = {12}, number = {5}, pages = {}, pmid = {36902702}, issn = {2077-0383}, support = {Not applicable//Ministry of Health of Italy/ ; }, abstract = {According to the World Health Organization's definition, long COVID is the persistence or development of new symptoms 3 months after the initial infection. Various conditions have been explored in studies with up to one-year follow-up but very few looked further. This prospective cohort study addresses the presence of a wide spectrum of symptoms in 121 patients hospitalized during the acute phase of COVID-19 infection, and the association between factors related to the acute phase of the disease and the presence of residual symptoms after one year or longer from hospitalization. The main results are as follows: (i) post-COVID symptoms persist in up to 60% of the patient population at a mean follow-up of 17 months; (ii) the most frequent symptoms are fatigue and dyspnea, but neuropsychological disturbances persist in about 30% of the patients (iii) when corrected for the duration of follow-up with a freedom-from-event analysis; only complete (2 doses) vaccination at the time of hospital admission remained independently associated with persistence of the major physical symptoms, while vaccination and previous neuropsychological symptoms remained independently associated with persistence of major neuropsychological symptoms.}, } @article {pmid36901516, year = {2023}, author = {Lulli, LG and Baldassarre, A and Chiarelli, A and Mariniello, A and Paolini, D and Grazzini, M and Mucci, N and Arcangeli, G}, title = {Physical Impact of SARS-CoV-2 Infection in a Population of Italian Healthcare Workers.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901516}, issn = {1660-4601}, mesh = {Male ; Humans ; Female ; Middle Aged ; *COVID-19 ; SARS-CoV-2 ; Cross-Sectional Studies ; *Musculoskeletal Pain ; Health Personnel ; Italy ; }, abstract = {SARS-CoV-2 infection often causes symptoms and illness that can last for months after the acute phase, i.e., so-called "Long COVID" or Post-acute COVID-19. Due to the high prevalence of SARS-CoV-2 infection among Healthcare Workers (HCWs), post-COVID-19 symptoms can be common and threaten workers' occupational health and healthcare systems' functioning. The aim of this cross-sectional, observational study was to present data related to post-COVID-19 outcomes in a population of HCWs infected by COVID-19 from October 2020 to April 2021, and to identify possible factors associated with the persistence of illness, such as gender, age, previous medical conditions, and features of acute illness. A total of 318 HCWs who had become infected by COVID-19 were examined and interviewed approximately two months after their recovery from the infection. The clinical examinations were performed by Occupational Physicians in accordance with a specific protocol at the Occupational Medicine Unit of a tertiary hospital in Italy. The mean age of the participants was 45 years old, and 66.7% of the workers were women while 33.3% were men; the sample mainly consisted of nurses (44.7%). During the medical examination, more than half of the workers mentioned that they had experienced multiple residual bouts of illness after the acute phase of infection. Men and women were similarly affected. The most reported symptom was fatigue (32.1%), followed by musculoskeletal pain (13.6%) and dyspnea (13.2%). In the multivariate analysis, dyspnea (p < 0.001) and fatigue (p < 0.001) during the acute stage of illness and the presence of any limitation in working activities, in the context of fitness for a work evaluation performed while the occupational medicine surveillance program was being conducted (p = 0.025), were independently associated with any post-COVID-19 symptoms, which were considered final outcomes. The main post-COVID-19 symptoms-dyspnea, fatigue, and musculoskeletal pain-showed significant associations with dyspnea, fatigue, and musculoskeletal pain experienced during the acute stage of infection, with the presence of limitations in working activities, and pre-existing pneumological diseases. A normal weight according to body mass index was a protective factor. The identification of vulnerable workers as those with limitations in working activities, pneumological diseases, a high BMI, and of an older age and the implementation of preventive measures are key factors for preserving Occupational Health. Fitness-to-work evaluations performed by Occupational Physicians can be considered a complex index of overall health and functionality that can identify workers who may suffer from relevant post-COVID-19 symptoms.}, } @article {pmid36901059, year = {2023}, author = {Calvache-Mateo, A and López-López, L and Martín-Núñez, J and Heredia-Ciuró, A and Granados-Santiago, M and Ortiz-Rubio, A and Valenza, MC}, title = {Pain and Clinical Presentation: A Cross-Sectional Study of Patients with New-Onset Chronic Pain in Long-COVID-19 Syndrome.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36901059}, issn = {1660-4601}, mesh = {Humans ; *Chronic Pain ; Cross-Sectional Studies ; Quality of Life ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {The aim of this study was to evaluate the characteristics of pain (i.e., pain intensity, pain interference, clinical presentation) in Long-COVID-19 patients and compare the location of pain between successfully recovered COVID-19 patients and healthy matched controls. A cross-sectional case-control study was carried out. Long-COVID-19 patients, age- and sex-matched patients with a history of COVID-19 who had successfully recovered, and healthy controls were included. Outcomes included were pain characteristics (Brief Pain Inventory and Short-Form McGill Pain Questionnaire) and clinical presentation (Widespread Pain Index and Euroqol-5 Dimensions 5 Levels Visual Analogue Scale). Sixty-nine patients with Long-COVID-19 syndrome, sixty-six successfully recovered COVID-19 patients, and sixty-seven healthy controls were evaluated. Patients with Long-COVID-19 syndrome showed greater pain intensity and interference. In addition, they showed worse quality of life and greater widespread pain, with the most frequent locations of pain being the neck, legs, and head. In conclusion, patients with Long-COVID-19 syndrome show a high prevalence of pain, characterized by widespread pain of moderate intensity and interference, with the most frequent locations being the neck, legs, and head, significantly affecting the quality of life of these patients.}, } @article {pmid36900938, year = {2023}, author = {Scholz, U and Bierbauer, W and Lüscher, J}, title = {Social Stigma, Mental Health, Stress, and Health-Related Quality of Life in People with Long COVID.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {5}, pages = {}, pmid = {36900938}, issn = {1660-4601}, mesh = {Humans ; Female ; Middle Aged ; Male ; *Social Stigma ; Mental Health ; Post-Acute COVID-19 Syndrome ; Quality of Life/psychology ; Cross-Sectional Studies ; SARS-CoV-2 ; *COVID-19 ; Depression/psychology ; }, abstract = {A considerable amount of people who have been infected with SARS-CoV-2 experience ongoing symptoms, a condition termed long COVID. This study examined nuanced experiences of social stigma in people with long COVID and their associations with perceived stress, depressive symptoms, anxiety, and mental and physical health-related quality of life (hrqol). A total of N = 253 participants with long COVID symptoms (mean age = 45.49, SD = 12.03; n = 224, 88.5% women) completed a cross-sectional online survey on overall social stigma and the subfacets enacted and perceived external stigma, disclosure concerns, and internalized stigma. Data were analysed using multiple regression and controlling for overall burden of consequences of long COVID, overall burden of symptoms of long COVID, and outcome-specific confounders. In line with our preregistered hypotheses, total social stigma was related to more perceived stress, more depressive symptoms, higher anxiety, and lower mental hrqol, but-in contrast to our hypothesis-it was unrelated to physical hrqol after controlling for confounders. The three subscales of social stigma resulted in differential associations with the outcomes. Social stigma experiences go hand in hand with worse mental health in people with long COVID. Future studies should examine potential protective factors to buffer the effects of social stigma on people's well-being.}, } @article {pmid36900026, year = {2023}, author = {Schaefer, LV and Bittmann, FN}, title = {The Adaptive Force as a Potential Biomechanical Parameter in the Recovery Process of Patients with Long COVID.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {36900026}, issn = {2075-4418}, support = {491466077//Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)/ ; }, abstract = {Long COVID patients show symptoms, such as fatigue, muscle weakness and pain. Adequate diagnostics are still lacking. Investigating muscle function might be a beneficial approach. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially sensitive for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients and their recovery process. AF parameters of elbow and hip flexors were assessed in 17 patients at three time points (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three time points. Symptom intensity decreased significantly from pre to end. The findings revealed a substantially impaired maximal holding capacity in long COVID patients, which returned to normal function with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.}, } @article {pmid36899992, year = {2023}, author = {Herrero-Montes, M and Fernández-de-Las-Peñas, C and Ferrer-Pargada, D and Izquierdo-Cuervo, S and Abascal-Bolado, B and Valera-Calero, JA and Paras-Bravo, P}, title = {Association of Kinesiophobia with Catastrophism and Sensitization-Associated Symptoms in COVID-19 Survivors with Post-COVID Pain.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {36899992}, issn = {2075-4418}, support = {LONG COVID EXP//Comunidad de Madrid/ ; Next-Val 2021//Instituto de Investigación Marqués de Valdecilla/ ; }, abstract = {Pain symptoms after the acute phase of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are present in almost 50% of COVID-19 survivors. The presence of kinesiophobia is a risk factor which may promote and perpetuate pain. This study aimed to investigate variables associated with the presence of kinesiophobia in a sample of previously hospitalized COVID-19 survivors exhibiting post-COVID pain. An observational study was conducted in three urban hospitals in Spain, including one hundred and forty-six COVID-19 survivors with post-COVID pain. Demographic (age, weight, height), clinical (intensity and duration of pain), psychological (anxiety level, depressive level, sleep quality), cognitive (catastrophizing), sensitization-associated symptoms, and health-related quality of life variables were collected in 146 survivors with post-COVID pain, as well as whether they exhibited kinesiophobia. Stepwise multiple linear regression models were conducted to identify variables significantly associated with kinesiophobia. Patients were assessed a mean of 18.8 (SD 1.8) months after hospital discharge. Kinesiophobia levels were positively associated with anxiety levels (r: 0.356, p < 0.001), depression levels (r: 0.306, p < 0.001), sleep quality (r: 0.288, p < 0.001), catastrophism (r: 0.578, p < 0.001), and sensitization-associated symptoms (r: 0.450, p < 0.001). The stepwise regression analysis revealed that 38.1% of kinesiophobia variance was explained by catastrophism (r[2] adj: 0.329, B = 0.416, t = 8.377, p < 0.001) and sensitization-associated symptoms (r[2] adj: 0.381, B = 0.130, t = 3.585, p < 0.001). Kinesiophobia levels were associated with catastrophism and sensitization-associated symptoms in previously hospitalized COVID-19 survivors with post-COVID pain. Identification of patients at a higher risk of developing a higher level of kinesiophobia, associated with post-COVID pain symptoms, could lead to better therapeutic strategies.}, } @article {pmid36899952, year = {2023}, author = {Leng, A and Shah, M and Ahmad, SA and Premraj, L and Wildi, K and Li Bassi, G and Pardo, CA and Choi, A and Cho, SM}, title = {Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899952}, issn = {2073-4409}, support = {K23 HL157610/HL/NHLBI NIH HHS/United States ; L30 HL165486/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; RNA, Viral ; *Nervous System Diseases/etiology ; Inflammation/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood-brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.}, } @article {pmid36899824, year = {2023}, author = {Theoharides, TC and Kempuraj, D}, title = {Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID.}, journal = {Cells}, volume = {12}, number = {5}, pages = {}, pmid = {36899824}, issn = {2073-4409}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Post-Acute COVID-19 Syndrome ; Microglia/metabolism ; Mast Cells/metabolism ; Inflammation ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae of SARS-CoV-2 (PASC), referred to as "Long-COVID," characterized by persistent physical and mental fatigue. However, the exact pathogenetic mechanisms affecting the brain are still not well-understood. There is increasing evidence of neurovascular inflammation in the brain. However, the precise role of the neuroinflammatory response that contributes to the disease severity of COVID-19 and long COVID pathogenesis is not clearly understood. Here, we review the reports that the SARS-CoV-2 spike protein can cause blood-brain barrier (BBB) dysfunction and damage neurons either directly, or via activation of brain mast cells and microglia and the release of various neuroinflammatory molecules. Moreover, we provide recent evidence that the novel flavanol eriodictyol is particularly suited for development as an effective treatment alone or together with oleuropein and sulforaphane (ViralProtek[®]), all of which have potent anti-viral and anti-inflammatory actions.}, } @article {pmid36896723, year = {2023}, author = {Fjaeldstad, AW and Ovesen, T and Stankevice, D and Ovesen, T}, title = {Olfactory training in long COVID-19 patients with lasting symptoms including olfactory dysfunction.}, journal = {Danish medical journal}, volume = {70}, number = {3}, pages = {}, pmid = {36896723}, issn = {2245-1919}, mesh = {Humans ; Smell ; Olfactory Training ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/complications ; *Olfaction Disorders/etiology/therapy ; }, abstract = {INTRODUCTION: Two-thirds of patients with COVID-19 developed smell and taste dysfunction, of whom half experienced improvement within the first month. After six months, 5-15% still suffered from significant olfactory dysfunction (OD). Before COVID-19, olfactory training (OT) was proved to be effective in patients with post-infectious OD. Therefore, the present study aimed to investigate the progress of olfactory recovery with and without OT in patients with long COVID-19.

METHODS: Consecutive patients with long COVID-19 referred to the Flavour Clinic at Gødstrup Regional Hospital, Denmark, were enrolled. The diagnostic set-up at the first visit and follow-up included smell and taste tests, questionnaires, ENT examination and instructions in OT.

RESULTS: From January 2021 to April 2022, 52 patients were included due to long COVID-19-related OD. The majority of patients complained of distorted sensory quality, in particular, parosmia. Two-thirds of the patients reported a subjective improvement of their sense of smell and taste along with a significant decline in the negative impact on quality of life (p = 0.0001). Retesting at follow-up demonstrated a significant increase in smell scores (p = 0.023) where a minimal clinically important difference (MCID) in smell scores was found in 23% of patients. Full training compliance was significantly associated with the probability of MCID improvement (OR = 8.13; p = 0.04).

CONCLUSIONS: The average effect of OT is modest; however, full training compliance was significantly associated with an increased probability of a clinically relevant olfactory improvement.

FUNDING: none.

TRIAL REGISTRATION: not relevant.}, } @article {pmid36893397, year = {2023}, author = {Randhawa, S and Alsamarrai, AJ and Lee, S and Somaratne, JB}, title = {Cardiac complications of COVID-19 infection.}, journal = {The New Zealand medical journal}, volume = {136}, number = {1571}, pages = {73-82}, doi = {10.26635/6965.6067}, pmid = {36893397}, issn = {1175-8716}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Pandemics ; Acute Disease ; New Zealand/epidemiology ; *Heart Diseases/epidemiology/etiology ; }, abstract = {Since the start of the COVID-19 pandemic, studies emerged reporting the occurrence of cardiovascular complications in patients affected by SARS-CoV-2. Initial data were likely skewed by higher risk populations and those with severe disease. Recent, larger studies have corroborated this association and provide estimates for risk of cardiovascular complications. Patients affected by COVID-19 are at increased risk of myocardial infarction, myocarditis, venous thromboembolism, arrhythmias, and exacerbation of heart failure. Furthermore, a subset of patients who recover from the acute illness have persistent symptoms, a condition termed "long COVID", and management of these symptoms is challenging. Clinicians treating patients affected by COVID-19 should remain vigilant for cardiac complications during the acute illness, particularly in high-risk populations.}, } @article {pmid36892678, year = {2023}, author = {Thurner, C and Stengel, A}, title = {Long-COVID syndrome: physical-mental interplay in the spotlight.}, journal = {Inflammopharmacology}, volume = {31}, number = {2}, pages = {559-564}, pmid = {36892678}, issn = {1568-5608}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/etiology/therapy ; Anxiety ; Depression ; }, abstract = {Patients suffering from Long-COVID syndrome experience a variety of different symptoms on a physical, but also on a psychological and social level. Previous psychiatric conditions such as depression and anxiety have been identified as separate risk factors for developing Long-COVID syndrome. This suggests a complex interplay of different physical and mental factors rather than a simple cause-effect relationship of a specific biological pathogenic process. The biopsychosocial model provides a foundation for understanding these interactions and integrating them into a broader perspective of the patient suffering from the disease instead of the individual symptoms, pointing towards the need of treatment options on a psychological as well as social level besides biological targets. This leads to our conclusion, that the biopsychosocial model should be the underlying philosophy of understanding, diagnosing and treating patients suffering from Long-COVID syndrome, moving away from the strictly biomedical understanding suspected by many patients, treaters and the media while also reducing the stigma still associated with the suggestion of a physical-mental interplay.}, } @article {pmid36891281, year = {2023}, author = {Khosla, S and Cheung, J and Gurubhagavatula, I and , }, title = {Sleep Assessment in Long COVID Clinics: A Necessary Tool for Effective Management.}, journal = {Neurology. Clinical practice}, volume = {13}, number = {1}, pages = {e200079}, pmid = {36891281}, issn = {2163-0402}, abstract = {As we adapt to SARS-CoV-2, it has become apparent that the acute illness is not the only threat from this virus. Long COVID has emerged as a potentially disabling condition with multiple varied symptoms. We propose that querying patients about their sleep may allow for the assessment of a sleep-related disorder that is amenable to treatment. In addition, hypersomnolence is a prominent feature and may mimic other organic hypersomnias; therefore, inquiring about COVID-19 infection in sleepy patients is suggested.}, } @article {pmid36891136, year = {2023}, author = {Pick, A}, title = {Is Long Covid a Functional Disorder?.}, journal = {Advances in rehabilitation science and practice}, volume = {12}, number = {}, pages = {11795727221141193}, pmid = {36891136}, issn = {2753-6351}, } @article {pmid36884145, year = {2023}, author = {Kumar, P and Jat, KR}, title = {Post-COVID-19 Sequelae in Children.}, journal = {Indian journal of pediatrics}, volume = {90}, number = {6}, pages = {605-611}, pmid = {36884145}, issn = {0973-7693}, mesh = {Adult ; Humans ; Child ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Communicable Disease Control ; Affect ; Cough ; Disease Progression ; }, abstract = {Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has been implicated in having post-COVID-19 sequelae in both adults and children. There is a lack of good data on the prevalence and risk factors for post-COVID-19 sequelae in children. The authors aimed to review the current literature on post-COVID sequelae. The prevalence of post-COVID sequelae in children is highly variable among studies, with an average of 25%. The sequelae may affect many organ systems, though mood symptoms, fatigue, cough, dyspnea, and sleep problems are common. In many studies, it is difficult to establish a causal association due to the lack of a control group. Furthermore, it is difficult to differentiate whether the neuropsychiatric symptoms in children after COVID-19 are due to infection or a result of lockdowns and social restrictions imposed by the pandemic. Children with COVID-19 should be followed by a multidisciplinary team and screened for symptoms, followed by focused laboratory evaluations as needed. There is no specific treatment for the sequelae. Only symptomatic and supportive treatment is required in most cases. More research is necessary to standardize the definitions of sequelae, establish a causal association, assess various treatment options, and the effects of different virus variants, and finally, see the impact of vaccination on the sequelae.}, } @article {pmid36880667, year = {2023}, author = {Gareau, MG and Barrett, KE}, title = {Role of the microbiota-gut-brain axis in postacute COVID syndrome.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {324}, number = {4}, pages = {G322-G328}, pmid = {36880667}, issn = {1522-1547}, support = {R01 AT009365/AT/NCCIH NIH HHS/United States ; }, mesh = {Humans ; *Brain-Gut Axis ; *COVID-19 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Disease Progression ; }, abstract = {The COVID-19 pandemic has resulted in the infection of hundreds of millions of individuals over the past 3 years, coupled with millions of deaths. Along with these more acute impacts of infection, a large subset of patients has developed symptoms that collectively comprise "postacute sequelae of COVID-19" (PASC, also known as long COVID), which can persist for months and maybe even years. In this review, we outline the current knowledge on the role of impaired microbiota-gut-brain (MGB) axis signaling in the development of PASC and the potential mechanisms involved, which may lead to a better understanding of disease progression and treatment options in the future.}, } @article {pmid36880317, year = {2023}, author = {Spence, NJ and Russell, D and Bouldin, ED and Tumminello, CM and Schwartz, T}, title = {Getting back to normal? Identity and role disruptions among adults with Long COVID.}, journal = {Sociology of health & illness}, volume = {45}, number = {4}, pages = {914-934}, doi = {10.1111/1467-9566.13628}, pmid = {36880317}, issn = {1467-9566}, mesh = {Adult ; Humans ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19 ; Chronic Disease ; Uncertainty ; }, abstract = {Long COVID is a novel chronic illness with a variety of symptoms that people who have labelled themselves 'long-haulers' experience for an extended duration following a COVID-19 infection. We draw on in-depth interviews conducted in March-April 2021 with 20 working-aged adults in the U.S. who self-identified as long-haulers to understand the consequences for identities. The results demonstrate that Long COVID has important consequences for identities and sense of self. Long-haulers described experiencing three stages of biographical disruptions: realising their illness experience as misaligned with sense of self and embodied, age-based expectations; facing challenges to identities and changes in social roles; and reconciling illness and identity in the context of an uncertain prognosis. It remains unclear how long-haulers will resolve biographical disruptions and identity conflicts, especially as scientific insights about this novel condition emerge. Such outcomes may depend largely on whether Long COVID remains a contested illness or medical knowledge progresses to improve their quality of life. For now, healthcare providers may approach Long COVID holistically to address the identity disruptions that long-haulers face as they manage the consequences of this chronic illness.}, } @article {pmid36879504, year = {2023}, author = {Opsteen, S and Files, JK and Fram, T and Erdmann, N}, title = {The role of immune activation and antigen persistence in acute and long COVID.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {71}, number = {5}, pages = {545-562}, pmid = {36879504}, issn = {1708-8267}, support = {K08 AI129705/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Convalescence ; SARS-CoV-2 ; Inflammation ; }, abstract = {In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%-20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4[+] and CD8[+] T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.}, } @article {pmid36879067, year = {2023}, author = {Muri, J and Cecchinato, V and Cavalli, A and Shanbhag, AA and Matkovic, M and Biggiogero, M and Maida, PA and Moritz, J and Toscano, C and Ghovehoud, E and Furlan, R and Barbic, F and Voza, A and De Nadai, G and Cervia, C and Zurbuchen, Y and Taeschler, P and Murray, LA and Danelon-Sargenti, G and Moro, S and Gong, T and Piffaretti, P and Bianchini, F and Crivelli, V and Podešvová, L and Pedotti, M and Jarrossay, D and Sgrignani, J and Thelen, S and Uhr, M and Bernasconi, E and Rauch, A and Manzo, A and Ciurea, A and Rocchi, MBL and Varani, L and Moser, B and Bottazzi, B and Thelen, M and Fallon, BA and Boyman, O and Mantovani, A and Garzoni, C and Franzetti-Pellanda, A and Uguccioni, M and Robbiani, DF}, title = {Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.}, journal = {Nature immunology}, volume = {24}, number = {4}, pages = {604-611}, pmid = {36879067}, issn = {1529-2916}, support = {198431/SNSF_/Swiss National Science Foundation/Switzerland ; P01 AI138938/AI/NIAID NIH HHS/United States ; U19 AI111825/AI/NIAID NIH HHS/United States ; U01 AI151698/AI/NIAID NIH HHS/United States ; 201369/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Autoantibodies ; Post-Acute COVID-19 Syndrome ; Chemokines ; }, abstract = {Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential.}, } @article {pmid36878599, year = {2023}, author = {Tanne, JH}, title = {Covid-19: US studies show racial and ethnic disparities in long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {535}, doi = {10.1136/bmj.p535}, pmid = {36878599}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Research ; }, } @article {pmid36877912, year = {2023}, author = {Song, Z and Giuriato, M}, title = {Demographic And Clinical Factors Associated With Long COVID.}, journal = {Health affairs (Project Hope)}, volume = {42}, number = {3}, pages = {433-442}, doi = {10.1377/hlthaff.2022.00991}, pmid = {36877912}, issn = {2694-233X}, support = {DP5 OD024564/OD/NIH HHS/United States ; U19 HS024072/HS/AHRQ HHS/United States ; }, mesh = {United States/epidemiology ; Humans ; Aged ; Female ; *COVID-19/epidemiology ; COVID-19 Testing ; Medicare ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Independent Living ; }, abstract = {Risk factors for postacute sequelae of SARS-CoV-2 infection ("long COVID") in community-dwelling populations remain poorly understood. Large-scale data, follow-up, comparison groups, and a consensus definition of long COVID are often lacking. Using data from the OptumLabs Data Warehouse on a nationwide sample of commercial and Medicare Advantage enrollees from the period January 2019 through March 2022, we examined demographic and clinical factors associated with long COVID, using two definitions of people who suffer symptoms long after they were first diagnosed with COVID-19 ("long haulers"). We identified 8,329 long haulers using the narrow definition (diagnosis code), 207,537 long haulers using the broad definition (symptom based), and 600,161 non-long haulers (comparison group). On average, long haulers were older and more likely female, with more comorbidities. Among narrow-definition long haulers, the leading risk factors for long COVID included hypertension, chronic lung disease, obesity, diabetes, and depression. Their time between initial COVID-19 diagnosis and diagnosis of long COVID averaged 250 days, with racial and ethnic differences. Broad-definition long haulers exhibited similar risk factors. Distinguishing long COVID from the progression of underlying conditions can be challenging, but further study may advance the evidence base related to the identification, causes, and consequences of long COVID.}, } @article {pmid36877677, year = {2023}, author = {Stephenson, T and Pinto Pereira, SM and Nugawela, MD and McOwat, K and Simmons, R and Chalder, T and Ford, T and Heyman, I and Swann, OV and Fox-Smith, L and Rojas, NK and Dalrymple, E and Ladhani, SN and Shafran, R and , }, title = {Long COVID-six months of prospective follow-up of changes in symptom profiles of non-hospitalised children and young people after SARS-CoV-2 testing: A national matched cohort study (The CLoCk) study.}, journal = {PloS one}, volume = {18}, number = {3}, pages = {e0277704}, pmid = {36877677}, issn = {1932-6203}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Child ; Adolescent ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis/epidemiology ; Cohort Studies ; Follow-Up Studies ; Dyspnea ; Fatigue ; Myalgia ; }, abstract = {BACKGROUND: Little is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no prospective follow-up to establish the pattern of symptoms over a 6-month time period.

METHODS: A non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11-17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP.

RESULTS: Three months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10-25% at testing to <3%. The prevalence of loss of smell declined from 21% to 5% at 3 months and 4% at 6 months. Prevalence of shortness of breath and tiredness also declined, but at a lower rate. Among test-negatives, the same common symptoms and trends were observed at lower prevalence's. Importantly, in some instances (shortness of breath, tiredness) the overall prevalence of specific individual symptoms at 3 and 6 months was higher than at PCR-testing because these symptoms were reported in new cohorts of CYP who had not reported the specific individual symptom previously.

CONCLUSIONS: In CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.}, } @article {pmid36876049, year = {2023}, author = {Bruzzone, C and Conde, R and Embade, N and Mato, JM and Millet, O}, title = {Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1111482}, pmid = {36876049}, issn = {2296-889X}, abstract = {COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.}, } @article {pmid36875356, year = {2023}, author = {Yuan, N and Lv, ZH and Sun, CR and Wen, YY and Tao, TY and Qian, D and Tao, FP and Yu, JH}, title = {Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1112383}, pmid = {36875356}, issn = {2296-2565}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Ageusia ; Anxiety ; Observational Studies as Topic ; }, abstract = {BACKGROUND: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors.

METHODS: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I [2] index were used to evaluate heterogeneity in this meta-analysis.

RESULTS: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients.

CONCLUSION: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.}, } @article {pmid36873058, year = {2023}, author = {Meißner, T}, title = {[Not Available].}, journal = {Die Heilberufe}, volume = {75}, number = {3}, pages = {36-37}, doi = {10.1007/s00058-023-3034-y}, pmid = {36873058}, issn = {0017-9604}, } @article {pmid36868374, year = {2023}, author = {Hilbold, E and Bär, C and Thum, T}, title = {COVID-19: Insights into long-term manifestations and lockdown impacts.}, journal = {Journal of sport and health science}, volume = {12}, number = {4}, pages = {438-463}, pmid = {36868374}, issn = {2213-2961}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; *Middle East Respiratory Syndrome Coronavirus ; Communicable Disease Control ; }, abstract = {Coronaviruses are pathogens thought to primarily affect the respiratory tracts of humans. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 was also marked mainly by its symptoms of respiratory illness, which were named coronavirus disease 2019 (COVID-19). Since its initial discovery, many other symptoms have been linked to acute SARS-CoV-2 infections as well as to the long-term outcomes of COVID-19 patients. Among these symptoms are different categories of cardiovascular diseases (CVDs), which continue to be the main cause of death worldwide. The World Health Organization estimates that 17.9 million people die from CVDs each year, accounting for ∼32% of all deaths globally. Physical inactivity is one of the most important behavioral risk factors for CVDs. The COVID-19 pandemic has affected CVDs as well as the physical activity in different ways. Here, we provide an overview of the current status as well as future challenges and possible solutions.}, } @article {pmid36867709, year = {2023}, author = {Rathgeb, C and Pawellek, M and Behrends, U and Alberer, M and Kabesch, M and Gerling, S and Brandstetter, S and Apfelbacher, C}, title = {The Evaluation of Health Care Services for Children and Adolescents With Post-COVID-19 Condition: Protocol for a Prospective Longitudinal Study.}, journal = {JMIR research protocols}, volume = {12}, number = {}, pages = {e41010}, pmid = {36867709}, issn = {1929-0748}, abstract = {BACKGROUND: Some children and adolescents suffer from late effects of a SARS-CoV-2 infection despite a frequently mild course of the disease. Nevertheless, extensive care for post-COVID-19 condition, also known as post-COVID-19 syndrome, in children and young people is not yet available. A comprehensive care network, Post-COVID Kids Bavaria (PoCo), for children and adolescents with post-COVID-19 condition has been set up as a model project in Bavaria, Germany.

OBJECTIVE: The aim of this study is to evaluate the health care services provided within this network structure of care for children and adolescents with post-COVID-19 condition in a pre-post study design.

METHODS: We have already recruited 117 children and adolescents aged up to 17 years with post-COVID-19 condition who were diagnosed and treated in 16 participating outpatient clinics. Health care use, treatment satisfaction, patient-reported outcomes related to health-related quality of life (the primary endpoint), fatigue, postexertional malaise, and mental health are being assessed at different time points (at baseline and after 4 weeks, 3 months, and 6 months) using routine data, interviews, and self-report questionnaires.

RESULTS: The study recruitment process ran from April 2022 until December 2022. Interim analyses will be carried out. A full analysis of the data will be conducted after follow-up assessment is completed, and the results will be published.

CONCLUSIONS: The results will contribute to the evaluation of therapeutic services provided for post-COVID-19 condition in children and adolescents, and avenues for optimizing care may be identified.

DERR1-10.2196/41010.}, } @article {pmid36866647, year = {2023}, author = {Tronco Hernandez, YA and Julian, A and Weekes, EC and Murphy, J and Frost, G and Hickson, M}, title = {Developing a consensus to support health and social care professionals and patients manage nutrition in the context of COVID-19 recovery.}, journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association}, volume = {36}, number = {4}, pages = {1242-1252}, doi = {10.1111/jhn.13163}, pmid = {36866647}, issn = {1365-277X}, mesh = {Humans ; *COVID-19 ; Health Personnel ; Social Support ; Delivery of Health Care ; Nutritional Status ; }, abstract = {BACKGROUND: The long-term effects on people who have had COVID-19 affect nutrition and can be influenced by diet conversely. Specific nutritional guidelines, however, were scarce at the beginning of 2020, and empirical literature was also lacking. Conventional research methodologies needed to be adapted to review the available literature that could be relevant to the United Kingdom and policy documents as well as collect the views of health and care staff. The aim of this paper is to describe the method to develop consensus statements from experts to address the necessary nutritional support and what emerged from this.

METHODS: A nominal group technique (NGT) was adapted to the virtual world; we purposefully selected a range of professionals (dietitians, nurses, occupational therapists, etc.) and patients with long-term effects of COVID to present them with the most updated evidence and aim to reach key guidelines to address COVID-19 recovery.

RESULTS: We were able to reach consensus statements that were developed and reviewed by relevant healthcare staff at the front line to address the nutritional needs of patients recovering from COVID-19 and those suffering from its long-term effects. This adapted NGT process led us to understand that a virtual repository of concise guidelines and recommendations was needed. This was developed to be freely accessed by both patients recovering from COVID-19 and health professionals who manage them.

CONCLUSIONS: We successfully obtained key consensus statements from the adapted NGT, which showed the need for the nutrition and COVID-19 knowledge hub. This hub has been developed, updated, reviewed, endorsed and improved across the subsequent 2 years.}, } @article {pmid36863719, year = {2023}, author = {O'Brien, KK and Brown, DA and McDuff, K and St Clair-Sullivan, N and Solomon, P and Chan Carusone, S and McCorkell, L and Wei, H and Goulding, S and O'Hara, M and Thomson, C and Roche, N and Stokes, R and Vera, JH and Erlandson, KM and Bergin, C and Robinson, L and Cheung, AM and Torres, B and Avery, L and Bannan, C and Harding, R}, title = {Conceptualising the episodic nature of disability among adults living with Long COVID: a qualitative study.}, journal = {BMJ global health}, volume = {8}, number = {3}, pages = {}, pmid = {36863719}, issn = {2059-7908}, support = {//CIHR/Canada ; }, mesh = {Humans ; Female ; Adult ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Ethnicity ; Ireland/epidemiology ; Qualitative Research ; }, abstract = {INTRODUCTION: Our aim was to describe episodic nature of disability among adults living with Long COVID.

METHODS: We conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We recruited participants via collaborator community organisations in Canada, Ireland, UK and USA.We recruited adults who self-identified as living with Long COVID with diversity in age, gender, race/ethnicity, sexual orientation and duration since initial COVID infection between December 2021 and May 2022. We used a semistructured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis.

RESULTS: Among the 40 participants, the median age was 39 years (IQR: 32-49); majority were women (63%), white (73%), heterosexual (75%) and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterised by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with 'ups and downs', 'flare-ups' and 'peaks' followed by 'crashes', 'troughs' and 'valleys', likened to a 'yo-yo', 'rolling hills' and 'rollercoaster ride' with 'relapsing/remitting', 'waxing/waning', 'fluctuations' in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterised as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health.

CONCLUSION: Among this sample of adults living with Long COVID, experiences of disability were described as episodic, characterised by fluctuating health challenges, which may be unpredictable in nature. Results can help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.}, } @article {pmid36861893, year = {2023}, author = {Willan, J and Agarwal, G and Bienz, N}, title = {Mortality and burden of post-COVID-19 syndrome have reduced with time across SARS-CoV-2 variants in haematology patients.}, journal = {British journal of haematology}, volume = {201}, number = {4}, pages = {640-644}, doi = {10.1111/bjh.18700}, pmid = {36861893}, issn = {1365-2141}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Hematology ; }, abstract = {Haematology patients contracting SARS-CoV-2 were identified at the start of the pandemic to be at higher risk of death or of persistent symptoms (post-COVID-19 syndrome). As variants with altered pathogenicity have emerged, uncertainty remains around how that risk has changed. We prospectively set up a dedicated post-COVID-19 clinic to monitor haematology patients infected with COVID-19 from the start of the pandemic. In total, 128 patients were identified and telephone interviews were conducted with 94 of 95 survivors. Ninety-day mortality attributed to COVID-19 has fallen sequentially from 42% for the Original and Alpha strains to 9% and to 2% for the Delta and Omicron variants respectively. Furthermore, the risk of post-COVID-19 syndrome in survivors has fallen from 46% for the Original or Alpha strains to 35% for Delta and 14% for the Omicron strain. Since vaccine uptake has been nearly universal in haematology patients, it is not possible to determine whether improved outcomes reflect the reduced pathogenicity of the virus, or widespread vaccine deployment. Whilst mortality and morbidity remain higher in haematology patients than in the general population, our data suggest that the absolute risks are now significantly lower. Given this trend, we believe clinicians should initiate conversations about risk with their patients on whether to maintain any self-imposed social isolation.}, } @article {pmid36861419, year = {2023}, author = {Porter, E}, title = {New year, new Future Microbiology: welcome to Volume 18.}, journal = {Future microbiology}, volume = {18}, number = {}, pages = {1-4}, doi = {10.2217/fmb-2023-0007}, pmid = {36861419}, issn = {1746-0921}, } @article {pmid36861061, year = {2023}, author = {Sasaki, N and Yamatoku, M and Tsuchida, T and Sato, H and Yamaguchi, K}, title = {Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction.}, journal = {Progress in rehabilitation medicine}, volume = {8}, number = {}, pages = {20230004}, pmid = {36861061}, issn = {2432-1354}, abstract = {OBJECTIVES: There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms.

METHODS: High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[[123]I]iodoamphetamine single photon emission computed tomography (SPECT) was performed.

RESULTS: Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS.

CONCLUSIONS: Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.}, } @article {pmid36858426, year = {2023}, author = {Taylor, L}, title = {Covid-19: Vaccination reduces severity and duration of long covid, study finds.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {491}, doi = {10.1136/bmj.p491}, pmid = {36858426}, issn = {1756-1833}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Vaccination ; }, } @article {pmid36858287, year = {2023}, author = {Hernández-Aceituno, A and García-Hernández, A and Larumbe-Zabala, E}, title = {COVID-19 long-term sequelae: Omicron versus Alpha and Delta variants.}, journal = {Infectious diseases now}, volume = {53}, number = {5}, pages = {104688}, pmid = {36858287}, issn = {2666-9919}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; }, abstract = {BACKGROUND: The study aimed to assess the association between three predominant SARS-CoV-2 variants (Alpha, Delta, and Omicron) and the risk of developing long COVID (persistence of physical, medical, and cognitive symptoms more than 4 weeks after infection), post-COVID-19 syndrome (symptoms extending beyond 12 weeks), and viral persistence (testing positive beyond 4 weeks despite clinical resolution).

METHODS: Retrospective study of 325 patients hospitalized for COVID-19 with genomic sequencing information. For each SARS-CoV-2 variant, sample characteristics, frequency of symptoms, and long-term sequelae were compared using Chi-squared test, Fisher's exact test, Kruskal-Wallis test, and Dunn's test as appropriate. Odds ratios (OR) were calculated using logistic regression models to assess the association of risk factors and sequelae.

RESULTS: The adjusted model showed that the Omicron (vs Alpha) variant (OR, 0.30; 95% CI 0.16-0.56), admission to ICU (OR, 1.14; 95% CI 1.05-1.23), and being treated with antiviral or immunomodulatory drugs (OR, 2.01; 95% CI 1.23-3.27) predicted long COVID and post-COVID-19 syndrome. Viral persistence showed no difference between variants.

CONCLUSIONS: The Omicron variant was associated with significantly lower odds of developing long-term sequelae from COVID-19 compared with previous variants, while severity of illness indicators increased the risk. Vaccination status, age, sex, and comorbidities were not found to predict sequelae development. This information has implications for both health managers and clinicians when deciding on the appropriate clinical management and subsequent outpatient follow-up of these patients. More studies with non-hospitalized patients are still necessary.}, } @article {pmid36857191, year = {2023}, author = {Fernández-de-Las-Peñas, C and Cuadrado, ML and Gómez-Mayordomo, V and García-Azorín, D and Arendt-Nielsen, L}, title = {Headache as a COVID-19 onset symptom or Post-COVID symptom according to the SARS-CoV-2 Variant.}, journal = {Expert review of neurotherapeutics}, volume = {23}, number = {2}, pages = {179-186}, doi = {10.1080/14737175.2023.2185138}, pmid = {36857191}, issn = {1744-8360}, mesh = {*Post-Acute COVID-19 Syndrome/complications/physiopathology/virology ; *Headache/etiology/physiopathology/virology ; *COVID-19/complications/physiopathology/virology ; Risk Factors ; Humans ; SARS-CoV-2 ; Animals ; Acute Disease ; }, abstract = {INTRODUCTION: COVID19 associated headaches are highly common and there is currently an unmet need to better understand their association with SARSCoV2 variants. Headaches are a prevalent symptom in the acute phase of COVID19 and are associated with a better prognosis and better immune response. They are also a relevant post-COVID symptom.

AREAS COVERED: This article analyses the differences in the prevalence of headache as an onset symptom and in post-COVID headache among the different SARS-CoV-2 variants: the historical strain, Alpha, Delta and Omicron. The different pathophysiological mechanisms by which SARS-CoV-2 infection may cause headache are also discussed.

EXPERT OPINION: The presence of headache at the acute phase is a risk factor for post-COVID headache, whereas a history of primary headache does not appear to be associated with post-COVID headache. The prevalence of headache as an onset symptom appears to be variable for the different SARS-CoV-2 variants, but current data are inconclusive. However, the current evidence also suggests that headache represents a prevalent symptom in the acute and post-infection COVID-19 phase, regardless of SARS-CoV-2 variant.}, } @article {pmid36857178, year = {2023}, author = {Fontes-Dantas, FL and Fernandes, GG and Gutman, EG and De Lima, EV and Antonio, LS and Hammerle, MB and Mota-Araujo, HP and Colodeti, LC and Araújo, SMB and Froz, GM and da Silva, TN and Duarte, LA and Salvio, AL and Pires, KL and Leon, LAA and Vasconcelos, CCF and Romão, L and Savio, LEB and Silva, JL and da Costa, R and Clarke, JR and Da Poian, AT and Alves-Leon, SV and Passos, GF and Figueiredo, CP}, title = {SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice.}, journal = {Cell reports}, volume = {42}, number = {3}, pages = {112189}, pmid = {36857178}, issn = {2211-1247}, mesh = {Humans ; Animals ; Mice ; *COVID-19/complications ; Spike Glycoprotein, Coronavirus/genetics ; SARS-CoV-2/metabolism ; Toll-Like Receptor 4 ; Post-Acute COVID-19 Syndrome ; *Cognitive Dysfunction ; }, abstract = {Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or its fragments are released from cells during infection, reaching different tissues, including the CNS, irrespective of the presence of the viral RNA. Here, we demonstrate that brain infusion of Spike protein in mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show that neuroinflammation and hippocampal microgliosis mediate Spike-induced memory dysfunction via complement-dependent engulfment of synapses. Genetic or pharmacological blockage of Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination and memory dysfunction induced by Spike brain infusion. Accordingly, in a cohort of 86 patients who recovered from mild COVID-19, the genotype GG TLR4-2604G>A (rs10759931) is associated with poor cognitive outcome. These results identify TLR4 as a key target to investigate the long-term cognitive dysfunction after COVID-19 infection in humans and rodents.}, } @article {pmid36856339, year = {2023}, author = {Philip, B and Mukherjee, P and Khare, Y and Ramesh, P and Zaidi, S and Sabry, H and Harky, A}, title = {COVID-19 and its long-term impact on the cardiovascular system.}, journal = {Expert review of cardiovascular therapy}, volume = {21}, number = {3}, pages = {211-218}, doi = {10.1080/14779072.2023.2184800}, pmid = {36856339}, issn = {1744-8344}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Cardiovascular System ; *Cardiovascular Diseases/diagnosis ; *Myocarditis ; }, abstract = {INTRODUCTION: TheSARS-CoV-2 virus caused a pandemic affecting healthcare deliveryglobally. Despite the presentation of COVID-19 infection beingfrequently dominated by respiratory symptoms; it is now notorious tohave potentially serious cardiovascular sequelae. This articleexplores current data to provide a comprehensive overview of thepathophysiology, cardiovascular risk factors, and implications ofCOVID-19.

AREAS COVERED: Inherentstructure of SARS-CoV-2, and its interaction with both ACE-2 andnon-ACE-2 mediated pathways have been implicated in the developmentof cardiovascular manifestations, progressively resulting in acuterespiratory distress syndrome, multiorgan failure, cytokine releasesyndrome, and subsequent myocardial damage. The interplay betweenexisting and de novo cardiac complications must be noted. Forindividuals taking cardiovascular medications, pharmacologicinteractions are a crucial component. Short-term cardiovascularimpacts include arrhythmia, myocarditis, pericarditis, heart failure,and thromboembolism, whereas long-term impacts include diabetes andhypertension. To identify suitable studies, a PubMed literaturesearch was performed including key words such as 'Covid 19,''Cardiovascular disease,' 'Long covid,' etc.

EXPERT OPINION: Moresophisticated planning and effective management for cardiologyhealthcare provision is crucial, especially for accommodatingchallenges associated with Long-COVID. With the potential applicationof AI and automated data, there are many avenues and sequelae thatcan be approached for investigation.}, } @article {pmid36855438, year = {2023}, author = {Channon-Wells, S and Vito, O and McArdle, AJ and Seaby, EG and Patel, H and Shah, P and Pazukhina, E and Wilson, C and Broderick, C and D'Souza, G and Keren, I and Nijman, RG and Tremoulet, A and Munblit, D and Ulloa-Gutierrez, R and Carter, MJ and Ramnarayan, P and De, T and Hoggart, C and Whittaker, E and Herberg, JA and Kaforou, M and Cunnington, AJ and Blyuss, O and Levin, M and , }, title = {Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.}, journal = {The Lancet. Rheumatology}, volume = {5}, number = {4}, pages = {e184-e199}, pmid = {36855438}, issn = {2665-9913}, support = {MRF_MRF-160-0008-ELP-KAFO-C0801/MRF/MRF/United Kingdom ; }, abstract = {BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.

METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.

FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups.

INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries.

FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health.}, } @article {pmid36855220, year = {2023}, author = {Albright, C and Limoges, J and Rempel, GR}, title = {Living with pulmonary sequelae of COVID-19 and the implications for clinical nursing practice: A qualitative systematised review.}, journal = {Journal of clinical nursing}, volume = {32}, number = {21-22}, pages = {7650-7660}, doi = {10.1111/jocn.16664}, pmid = {36855220}, issn = {1365-2702}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Qualitative Research ; *Nursing Care ; Clinical Competence ; }, abstract = {AIM: To synthesise qualitative research on pulmonary sequelae of COVID-19 and identify patient needs and experiences to develop nursing care strategies.

BACKGROUND: Qualitative research on long COVID by subtype has not yet occurred. As pulmonary sequelae constitute a serious long COVID subtype, exploring patient experience and needs can generate knowledge to guide nursing practice.

DESIGN: Systematised review methodology utilised on a purposive sample of published articles and reported using the PRISMA guidelines and checklists. Searched MEDLINE, Cumulative Index to Nursing and Allied Health, and Google Scholar, for English or French articles published from February 2020 to June 2022; qualitative research with adults recovering from COVID-19 with evidence of pulmonary sequelae.

METHODS: Established principles for data extraction followed related to data reduction, data presentation, data comparison, and conclusion formulation and verification. Analysis was informed by Thorne's Interpretive Description and extended with Meleis' transitions theory, Mishel's uncertainty in illness theory and Moore et al.'s holistic theory of unpleasant symptoms. The quality of included studies was assessed Joanna Briggs Institute critical appraisal tool for qualitative research.

RESULTS: Four articles with six pooled participants provided data to yield three main themes: (1) a novel health-illness transition, (2) lung injury and pulmonary fibrosis as antecedent to illness uncertainty, (3) and pulmonary symptoms that are compounded by fatigue and weakness.

CONCLUSION: Pulmonary sequelae of COVID-19 confers a unique health-illness transition, uncertainties and symptoms that can be addressed by theory informed nursing practice.

Advocacy, optimising the nurse-patient relationship, offering up-to-date information and addressing uncertainty may help patients cope with pulmonary sequelae, a complex subtype of long COVID with important considerations for clinical nursing care. Despite a lack of evidence-informed clinical pathways, nurses can support patients to understand novel treatments, support discharge planning and acknowledge the synergistic nature of pulmonary symptoms and fatigue to support health-illness transitions.

This article involved analysis of previously published works.}, } @article {pmid36855180, year = {2023}, author = {Oka, T}, title = {A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report.}, journal = {BioPsychoSocial medicine}, volume = {17}, number = {1}, pages = {8}, pmid = {36855180}, issn = {1751-0759}, abstract = {BACKGROUND: Some patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complain of persistent fatigue, dyspnea, pain, and cognitive dysfunction. These symptoms are often described as "long COVID". Whether a patient with long COVID might develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is of interest, as is the treatment and management of ME/CFS in a post-COVID patient. Here I report a patient, who, after an infection with SARS-CoV-2, developed ME/CFS and recovered after treatment.

CASE PRESENTATION: The patient was a previously healthy 55-year-old woman who worked as a nurse and became ill with COVID-19 pneumonia. She then presented with severe fatigue, post-exertional malaise, dyspnea, pain, cognitive dysfunction, tachycardia, and exacerbation of fatigue on physical exertion, which persisted for more than 6 months after her recovery from COVID-19 pneumonia. She was bedridden for more than half of each day. The patient was treated from multiple perspectives, which included (1) instructions on eating habits and supplements; (2) cognitive and behavioral modifications for coping with physical, emotional, and cognitive fatigue; (3) instructions on conditioning exercises to improve deconditioning due to fatigue and dyspnea; and (4) pharmacotherapy with amitriptyline and hochuekkito, a Japanese herbal (Kampo) medicine. The patient made a complete recovery after completing the prescribed regimen and was able to return to work as a nurse.

CONCLUSIONS: To the best of my knowledge, this is the first detailed report on a patient infected with SARS-CoV-2 followed by long COVID with the signs/symptoms of ME/CFS who recovered after treatment. I hope this case report will be helpful to health care practitioners by its presentation of some of the therapeutic options for alleviating disabling signs/symptoms in patients with post-COVID ME/CFS.}, } @article {pmid37564950, year = {2022}, author = {Ninham, B and Reines, B and Battye, M and Thomas, P}, title = {Pulmonary surfactant and COVID-19: A new synthesis.}, journal = {QRB discovery}, volume = {3}, number = {}, pages = {e6}, pmid = {37564950}, issn = {2633-2892}, abstract = {CHAPTER 1: COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2; as these produce pulmonary surfactant (PS), the possibility that insufficient PS plays a role in COVID-19 pathogenesis has been raised. However, the opposite of predicted high alveolar surface tension is found in many early COVID-19 patients: paradoxically normal lung volumes and high compliance occur, with profound hypoxemia. That 'COVID anomaly' was quickly rationalised by invoking traditional vascular mechanisms-mainly because of surprisingly preserved alveolar surface in early hypoxemic cases. However, that quick rejection of alveolar damage only occurred because the actual mechanism of gas exchange has long been presumed to be non-problematic, due to diffusion through the alveolar surface. On the contrary, we provide physical chemical evidence that gas exchange occurs by an process of expansion and contraction of the three-dimensional structures of PS and its associated proteins. This view explains anomalous observations from the level of cryo-TEM to whole individuals. It encompasses results from premature infants to the deepest diving seals. Once understood, the COVID anomaly dissolves and is straightforwardly explained as covert viral damage to the 3D structure of PS, with direct treatment implications. As a natural experiment, the SARS-CoV-2 virus itself has helped us to simplify and clarify not only the nature of dyspnea and its relationship to pulmonary compliance, but also the fine detail of the PS including such features as water channels which had heretofore been entirely unexpected.

CHAPTER 2: For a long time, physical, colloid and surface chemistry have not intersected with physiology and cell biology as much as we might have hoped. The reasons are starting to become clear. The discipline of physical chemistry suffered from serious unrecognised omissions that rendered it ineffective. These foundational defects included omission of specific ion molecular forces and hydration effects. The discipline lacked a predictive theory of self-assembly of lipids and proteins. Worse, theory omitted any role for dissolved gases, O2, N2, CO2, and their existence as stable nanobubbles above physiological salt concentration. Recent developments have gone some way to explaining the foam-like lung surfactant structures and function. It delivers O2/N2 as nanobubbles, and efflux of CO2, and H2O nanobubbles at the alveolar surface. Knowledge of pulmonary surfactant structure allows an explanation of the mechanism of corona virus entry, and differences in infectivity of different variants. CO2 nanobubbles, resulting from metabolism passing through the molecular frit provided by the glycocalyx of venous tissue, forms the previously unexplained foam which is the endothelial surface layer. CO2 nanobubbles turn out to be lethal to viruses, providing a plausible explanation for the origin of 'Long COVID'. Circulating nanobubbles, stable above physiological 0.17 M salt drive various enzyme-like activities and chemical reactions. Awareness of the microstructure of Pulmonary Surfactant and that nanobubbles of (O2/N2) and CO2 are integral to respiratory and circulatory physiology provides new insights to the COVID-19 and other pathogen activity.}, } @article {pmid37168753, year = {2022}, author = {Arostegui, D and Castro, K and Schwarz, S and Vaidy, K and Rabinowitz, S and Wallach, T}, title = {Persistent SARS-CoV-2 Nucleocapsid Protein Presence in the Intestinal Epithelium of a Pediatric Patient 3 Months After Acute Infection.}, journal = {JPGN reports}, volume = {3}, number = {1}, pages = {e152}, pmid = {37168753}, issn = {2691-171X}, abstract = {In addition to the severe impact of acute respiratory disease during the SARS-CoV-2 pandemic, the issue of "Long COVID" illness has impacted large numbers of patients following the initial infection. Wide ranges of Long Covid incidence have been reported, ranging from 30 to 87%. Long COVID has a variety of clinical manifestations, including gastrointestinal symptoms. Here, we report a case of persistent abdominal pain, 3 months following a SARS-CoV-2 diagnosis, associated with chronic colonic inflammation and the presence of mucosal SARS-CoV-2 virions.}, } @article {pmid36962089, year = {2021}, author = {Mulberry, N and Tupper, P and Kirwin, E and McCabe, C and Colijn, C}, title = {Vaccine rollout strategies: The case for vaccinating essential workers early.}, journal = {PLOS global public health}, volume = {1}, number = {10}, pages = {e0000020}, pmid = {36962089}, issn = {2767-3375}, abstract = {In vaccination campaigns against COVID-19, many jurisdictions are using age-based rollout strategies, reflecting the much higher risk of severe outcomes of infection in older groups. In the wake of growing evidence that approved vaccines are effective at preventing not only adverse outcomes, but also infection, we show that such strategies are less effective than strategies that prioritize essential workers. This conclusion holds across numerous outcomes, including cases, hospitalizations, Long COVID (cases with symptoms lasting longer than 28 days), deaths and net monetary benefit. Our analysis holds in regions where the vaccine supply is limited, and rollout is prolonged for several months. In such a setting with a population of 5M, we estimate that vaccinating essential workers sooner prevents over 200,000 infections, over 600 deaths, and produces a net monetary benefit of over $500M.}, } @article {pmid36853484, year = {2023}, author = {El-Tallawy, SN and Perglozzi, JV and Ahmed, RS and Kaki, AM and Nagiub, MS and LeQuang, JK and Hadarah, MM}, title = {Pain Management in the Post-COVID Era-An Update: A Narrative Review.}, journal = {Pain and therapy}, volume = {12}, number = {2}, pages = {423-448}, pmid = {36853484}, issn = {2193-8237}, abstract = {An extensive computer search (from January 2020 to January 2023) was conducted including literature from the PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID (over 6 months) is demonstrated, the term "long-COVID" is used. Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches. All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID. Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on the patients, health care systems, and society as well. Therefore, it is important that patients with chronic pain receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description about the post-COVID pain and to explore the impact of long COVID-19 on chronic pain patients, and also to give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.}, } @article {pmid36851793, year = {2023}, author = {Goretzki, SC and Brasseler, M and Dogan, B and Hühne, T and Bernard, D and Schönecker, A and Steindor, M and Gangfuß, A and Della Marina, A and Felderhoff-Müser, U and Dohna-Schwake, C and Bruns, N}, title = {High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study.}, journal = {Viruses}, volume = {15}, number = {2}, pages = {}, pmid = {36851793}, issn = {1999-4915}, mesh = {Adult ; Humans ; Adolescent ; Child ; *Post-Acute COVID-19 Syndrome ; Prevalence ; Cohort Studies ; Retrospective Studies ; *COVID-19/diagnosis/epidemiology ; }, abstract = {BACKGROUND: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients.

MATERIALS AND METHODS: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated.

RESULTS: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91-1.00) and a negative predictive value of 0.97 (0.92-1.00) for LC.

DISCUSSION/CONCLUSIONS: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC.}, } @article {pmid36851746, year = {2023}, author = {Yan, MZ and Yang, M and Lai, CL}, title = {Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management.}, journal = {Viruses}, volume = {15}, number = {2}, pages = {}, pmid = {36851746}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnosis ; Disease Outbreaks ; Disease Progression ; COVID-19 Testing ; }, abstract = {The COVID-19 outbreak was first reported in 2019, causing massive morbidity and mortality. The majority of the COVID-19 patients survived and developed Post-COVID-19 Syndrome (PC19S) of varying severity. Currently, the diagnosis of PC19S is achieved through history and symptomatology that cannot be explained by an alternative diagnosis. However, the heavy reliance on subjective reporting is prone to reporting errors. Besides, there is no unified diagnostic assessment tool to classify the clinical severity of patients. This leads to significant difficulties when managing patients in terms of public resource utilization, clinical progression monitorization and rehabilitation plan formulation. This narrative review aims to review current evidence of diagnosis based on triple assessment: clinical symptomatology, biochemical analysis and imaging evidence. Further assessment tools can be developed based on triple assessment to monitor patient's clinical progression, prognosis and intervals of monitoring. It also highlights the high-risk features of patients for closer and earlier monitoring. Rehabilitation programs and related clinical trials are evaluated; however, most of them focus on cardiorespiratory fitness and psychiatric presentations such as anxiety and depression. Further research is required to establish an objective and comprehensive assessment tool to facilitate clinical management and rehabilitation plans.}, } @article {pmid36851614, year = {2023}, author = {Vojdani, A and Vojdani, E and Saidara, E and Maes, M}, title = {Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID.}, journal = {Viruses}, volume = {15}, number = {2}, pages = {}, pmid = {36851614}, issn = {1999-4915}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Herpesvirus 4, Human ; *Herpesvirus 6, Human ; Autoimmunity ; *Fatigue Syndrome, Chronic ; *Epstein-Barr Virus Infections/complications ; SARS-CoV-2 ; Inflammation ; }, abstract = {A novel syndrome called long-haul COVID or long COVID is increasingly recognized in a significant percentage of individuals within a few months after infection with SARS-CoV-2. This disorder is characterized by a wide range of persisting, returning or even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine and systemic. Some overlapping symptomatologies exist between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Very much like with long ME/CFS, infections with herpes family viruses, immune dysregulation, and the persistence of inflammation have been reported as the most common pattern for the development of long COVID. This review describes several factors and determinants of long COVID that have been proposed, elaborating mainly on viral persistence, reactivation of latent viruses such as Epstein-Barr virus and human herpesvirus 6 which are also associated with the pathology of ME/CFS, viral superantigen activation of the immune system, disturbance in the gut microbiome, and multiple tissue damage and autoimmunity. Based on these factors, we propose diagnostic strategies such as the measurement of IgG and IgM antibodies against SARS-CoV-2, EBV, HHV-6, viral superantigens, gut microbiota, and biomarkers of autoimmunity to better understand and manage this multi-factorial disorder that continues to affect millions of people in the world.}, } @article {pmid36851359, year = {2023}, author = {Gärtner, BC and Klemis, V and Schmidt, T and Sester, M and Meyer, T}, title = {Transient Positive SARS-CoV-2 PCR without Induction of Systemic Immune Responses.}, journal = {Vaccines}, volume = {11}, number = {2}, pages = {}, pmid = {36851359}, issn = {2076-393X}, support = {no grant number//Deutsche Fußball Liga/ ; }, abstract = {SARS-CoV-2 testing is dominated by PCR to guide treatment and individual as well as public health preventive measures. Among 1700 football (soccer) players and staff of the German Bundesliga and Bundesliga 2 who were regularly tested by PCR twice weekly, 98 individuals had a positive PCR (May 2020 to mid-January 2021). A subset of these were retested shortly after the initial positive result. Among those, 11 subjects were identified who only had a transient single positive PCR of low viral load. All individuals were asymptomatic and none developed long COVID. We tested SARS-CoV-2 IgG and IgA as well as SARS-CoV-2 specific CD4 und CD8 positive T cells, and showed that only one out of 11 individuals developed SARS-CoV-2 specific cellular and humoral immunity after the positive PCR, whereas a specific immunity was undetectable in all other individuals. Thus, a single positive PCR might indicate that transient colonization of the upper respiratory tract with SARS-CoV-2 may occur without systemic induction of specific adaptive immunity. Together with test artifacts as another potential reason for a transiently positive test, this finding may favor cautious interpretation of positive PCR results or retesting before initiating intervening treatment or infection control measures in some cases.}, } @article {pmid36850042, year = {2024}, author = {Fjone, KS and Buanes, EA and Småstuen, MC and Laake, JH and Stubberud, J and Hofsø, K}, title = {Post-traumatic stress symptoms six months after ICU admission with COVID-19: Prospective observational study.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {103-114}, doi = {10.1111/jocn.16665}, pmid = {36850042}, issn = {1365-2702}, support = {312712/CR, 2020//Norges Forskningsråd/ ; }, mesh = {Humans ; Female ; *COVID-19/epidemiology ; *Stress Disorders, Post-Traumatic/psychology ; Intensive Care Units ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {AIMS AND OBJECTIVES: The aim of this study was to investigate the prevalence of post-traumatic stress symptoms, and to identify possible predictive factors in Norwegian intensive care unit survivors, 6 months after admission to the intensive care unit with COVID-19.

BACKGROUND: The SARS CoV-2 virus causing COVID-19 has spread worldwide since it was declared a pandemic in March 2020. The most severely ill patients have been treated in the intensive care due to acute respiratory failure and also acute respiratory distress syndrome. It is well documented that these severe conditions can lead to complex and long-lasting symptoms, such as psychological distress, and was, therefore, investigated for the specific COVID-19 population.

DESIGN: Prospective observational study.

METHODS: Clinical data and patient reported outcome measures were collected by the Norwegian Intensive Care and Pandemic Registry and by the study group 6 months after admission to an intensive care unit.

RESULTS: Among 222 COVID-19 patients admitted to Norwegian intensive care units between 10 March and 6 July 2020, 175 survived. The study sample consisted of 131 patients who responded to at least one patient reported outcome measure at 6 months following admission. The primary outcome was self-reported post-traumatic stress symptoms, using the Impact of Event Scale-6 (n = 89). Of those, 22.5% reported post-traumatic stress symptoms 6 months after admission. Female gender, younger age and having a high respiratory rate at admission were statistically significant predictive factors for reporting post-traumatic stress symptoms.

CONCLUSIONS: The result is in accordance with previously published research with comparable populations, suggesting that for many COVID-19 survivors psychological distress is a part of the post-acute sequelae. Results from the present study should be replicated in larger datasets.

This project provides important insight to post-acute sequelae after COVID-19 that patients may experience after critical illness.}, } @article {pmid36848564, year = {2023}, author = {Cui, L and Fang, Z and De Souza, CM and Lerbs, T and Guan, Y and Li, I and Charu, V and Chen, SY and Weissman, I and Wernig, G}, title = {Innate immune cell activation causes lung fibrosis in a humanized model of long COVID.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {10}, pages = {e2217199120}, pmid = {36848564}, issn = {1091-6490}, support = {SPO182437//Boehringer Ingelheim (BI)/ ; SPO134886//National Scleroderma Foundation (SF)/ ; }, mesh = {Humans ; Animals ; Mice ; *Pulmonary Fibrosis/etiology ; Post-Acute COVID-19 Syndrome ; CD47 Antigen ; Interleukin-6/genetics ; *COVID-19 ; Immunity, Innate ; }, abstract = {COVID-19 remains a global pandemic of an unprecedented magnitude with millions of people now developing "COVID lung fibrosis." Single-cell transcriptomics of lungs of patients with long COVID revealed a unique immune signature demonstrating the upregulation of key proinflammatory and innate immune effector genes CD47, IL-6, and JUN. We modeled the transition to lung fibrosis after COVID and profiled the immune response with single-cell mass cytometry in JUN mice. These studies revealed that COVID mediated chronic immune activation reminiscent to long COVID in humans. It was characterized by increased CD47, IL-6, and phospho-JUN (pJUN) expression which correlated with disease severity and pathogenic fibroblast populations. When we subsequently treated a humanized COVID lung fibrosis model by combined blockade of inflammation and fibrosis, we not only ameliorated fibrosis but also restored innate immune equilibrium indicating possible implications for clinical management of COVID lung fibrosis in patients.}, } @article {pmid36846611, year = {2023}, author = {Durstenfeld, MS and Peluso, MJ and Peyser, ND and Lin, F and Knight, SJ and Djibo, A and Khatib, R and Kitzman, H and O'Brien, E and Williams, N and Isasi, C and Kornak, J and Carton, TW and Olgin, JE and Pletcher, MJ and Marcus, GM and Beatty, AL}, title = {Factors Associated With Long COVID Symptoms in an Online Cohort Study.}, journal = {Open forum infectious diseases}, volume = {10}, number = {2}, pages = {ofad047}, pmid = {36846611}, issn = {2328-8957}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID.

METHODS: In March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise.

RESULTS: Of 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents' mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20-1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02-2.63), preinfection depression (OR, 1.08; 95% CI, 1.01-1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15-0.90) were associated with Long COVID symptoms.

CONCLUSIONS: Variant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms.}, } @article {pmid36846562, year = {2022}, author = {Patcai, J}, title = {Is 'Long Covid' similar to 'Long SARS'?.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac002}, pmid = {36846562}, issn = {2633-6960}, } @article {pmid36846561, year = {2022}, author = {Haunhorst, S and Bloch, W and Wagner, H and Ellert, C and Krüger, K and Vilser, DC and Finke, K and Reuken, P and Pletz, MW and Stallmach, A and Puta, C}, title = {Long COVID: a narrative review of the clinical aftermaths of COVID-19 with a focus on the putative pathophysiology and aspects of physical activity.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac006}, pmid = {36846561}, issn = {2633-6960}, abstract = {The pandemic coronavirus disease 2019 (COVID-19) can cause multi-systemic symptoms that can persist beyond the acute symptomatic phase. The post-acute sequelae of COVID-19 (PASC), also referred to as long COVID, describe the persistence of symptoms and/or long-term complications beyond 4 weeks from the onset of the acute symptoms and are estimated to affect at least 20% of the individuals infected with SARS-CoV-2 regardless of their acute disease severity. The multi-faceted clinical picture of long COVID encompasses a plethora of undulating clinical manifestations impacting various body systems such as fatigue, headache, attention disorder, hair loss and exercise intolerance. The physiological response to exercise testing is characterized by a reduced aerobic capacity, cardiocirculatory limitations, dysfunctional breathing patterns and an impaired ability to extract and use oxygen. Still, to this day, the causative pathophysiological mechanisms of long COVID remain to be elucidated, with long-term organ damage, immune system dysregulation and endotheliopathy being among the hypotheses discussed. Likewise, there is still a paucity of treatment options and evidence-based strategies for the management of the symptoms. In sum, this review explores different aspects of long COVID and maps the literature on what is known about its clinical manifestations, potential pathophysiological mechanisms, and treatment options.}, } @article {pmid36846556, year = {2022}, author = {Kavanagh, E}, title = {Long Covid brain fog: a neuroinflammation phenomenon?.}, journal = {Oxford open immunology}, volume = {3}, number = {1}, pages = {iqac007}, pmid = {36846556}, issn = {2633-6960}, abstract = {Neuroinflammation is a process triggered by an attack on the immune system. Activation of microglia in response to an immune system challenge can lead to a significant impact on cognitive processes, such as learning, memory and emotional regulation. Long Covid is an ongoing problem, affecting an estimated 1.3 million people within the UK alone, and one of its more significant, and as yet unexplained, symptoms is brain fog. Here, we discuss the potential role of neuroinflammation in Long Covid cognitive difficulties. Inflammatory cytokines have been found to play a significant role in reductions in LTP and LTD, a reduction in neurogenesis, and in dendritic sprouting. The potential behavioural consequences of such impacts are discussed. It is hoped that this article will allow for greater examination of the effects of inflammatory factors on brain function, most particularly in terms of their role in chronic conditions.}, } @article {pmid36846164, year = {2023}, author = {Camporesi, A and Soares Lanziotti, V and Bulut, Y and Behrens, D and Buonsenso, D}, title = {Editorial: Covid, Long Covid, Mental Health, Schools and Masks: how and why we failed child health communication during a pandemic.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1104518}, pmid = {36846164}, issn = {2296-2360}, } @article {pmid36844799, year = {2023}, author = {McDonald, S and Blackie, LER}, title = {A Theoretical Qualitative Investigation Exploring Illness Perceptions and Decision-Making About COVID-19 in an Ethnically Diverse UK-Based Sample.}, journal = {Patient preference and adherence}, volume = {17}, number = {}, pages = {473-489}, pmid = {36844799}, issn = {1177-889X}, abstract = {PURPOSE: The primary aim of the present investigation was to explore perceptions, experiences, and decision-making relating to the COVID-19 illness as the UK entered into a phase of "living safely with COVID-19". A secondary aim was to explore how perceptions around the COVID-19 vaccine might vary by ethnicity.

PARTICIPANTS AND METHODS: We adopted a qualitative approach with a diverse sample of UK-based participants. One-hundred-and-ninety-three individuals completed an online survey measuring perceptions towards COVID-19 with questions conceptualized through the Common-Sense Model of Self-Regulation.

RESULTS: Through deductive thematic analysis we identified one overarching theme in our data, "The transition back to normal routines", with four themes illustrating individuals' perceptions and experiences with COVID-19: 1) "Living with the uncertainty", 2) "Concern for others", 3) "The multiple consequences of COVID-19", and 4) "Sense of control", with the sub-theme of "Should I vaccinate, should I not vaccinate?".

CONCLUSION: Findings from the present investigation provide key insights for understanding how people's perceptions of COVID-19 during this transition period might impact their decisions and behavior moving forward. Specifically, findings suggest some prevailing concerns around catching the virus, while no strong qualitative evidence for concerns over long COVID were identified in this sample, the responsibility felt by individuals towards taking their own precautionary measures in light of the easing of all national restrictions, and some potential differences in perceptions towards the vaccine between individuals from different ethnic backgrounds.}, } @article {pmid36844201, year = {2023}, author = {Patterson, BK and Yogendra, R and Guevara-Coto, J and Mora-Rodriguez, RA and Osgood, E and Bream, J and Parikh, P and Kreimer, M and Jeffers, D and Rutland, C and Kaplan, G and Zgoda, M}, title = {Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC).}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1122529}, pmid = {36844201}, issn = {2296-858X}, abstract = {Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants' response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.}, } @article {pmid36843458, year = {2023}, author = {Levin, OS and Vashchilin, VV and Pikija, S and Khasanova, DR and Turuspekova, ST and Bogolepova, AN and Shmonin, AA and Maltceva, MN and Vozniuk, IA and Yanishevskiy, SN and Huseynov, DK and Karakulova, YV and Obidov, FK}, title = {[Current approaches in the treatment and rehabilitation of patients with neurological diseases after COVID-19. Resolution of the International Experts Forum].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {123}, number = {2}, pages = {44-51}, doi = {10.17116/jnevro202312302144}, pmid = {36843458}, issn = {1997-7298}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Pandemics ; *Nervous System Diseases/diagnosis ; }, abstract = {Despite the significant shift in global attention away from the pandemic, the problem of a new coronavirus infection remains important in the medical community. Almost 3 years after the start of the COVID-19 pandemic the issues of rehabilitation and management of delayed manifestations and sequelae of the disease are especially important. According to numerous available data, the new coronavirus infection is characterized by multiorgan lesions. Respiratory dysfunction, clotting disorders, myocardial dysfunction and various arrhythmias, acute coronary syndrome, acute renal failure, GI disorders, hepatocellular damage, hyperglycemia and ketosis, dermatological complications, ophthalmological symptoms and neurological disorders may be found. Significant prevalence of the latter in the post-coronavirus period necessitated this International Expert Forum to develop unified approaches to the management of patients with neurological complications and sequelae of new coronavirus infection based on practical experience and considering the scientific information available on COVID-19. The expert council developed a resolution formulating the tactics for the management of patients with neurological manifestations of COVID-19.}, } @article {pmid36843369, year = {2023}, author = {Fajloun, Z and Abi Khattar, Z and Kovacic, H and Legros, C and Sabatier, JM}, title = {Understanding and Relieving of Neuropathic Disorders in the Long COVID.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {4}, pages = {e270223214061}, doi = {10.2174/1871526523666230227113205}, pmid = {36843369}, issn = {2212-3989}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36842501, year = {2023}, author = {Sperling, S and Leth, S and Fløe, A and Hyldgaard, C and Gissel, T and Topcu, A and Kristensen, L and Sønderskov Dahl, L and Martin Schmid, J and Jensen-Fangel, S and Bendstrup, E}, title = {Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.}, journal = {Infectious diseases now}, volume = {53}, number = {6}, pages = {104686}, pmid = {36842501}, issn = {2666-9919}, mesh = {Humans ; Male ; Middle Aged ; Female ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Follow-Up Studies ; Prospective Studies ; Hospitalization ; }, abstract = {OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19.

METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published.

RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time.

CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.}, } @article {pmid36842195, year = {2023}, author = {Brunner-Ziegler, S and Bäuerle, M and Brühl, P and Kornek, G and Parschalk, B and Savic, R and Schnetzinger, M and Spath, T and Straßl, RP and Handisurya, A and Thalhammer, F}, title = {Long COVID symptoms in hospital employees after post-vaccination SARS-CoV-2 infection in Austria: A study on self-reported incidence and associated factors.}, journal = {Journal of infection and public health}, volume = {16}, number = {4}, pages = {596-602}, pmid = {36842195}, issn = {1876-035X}, mesh = {Male ; Female ; Humans ; Adult ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Self Report ; Austria/epidemiology ; Incidence ; SARS-CoV-2 ; Disease Progression ; Vaccination ; Hospitals ; }, abstract = {PURPOSE: Post acute sequelae of SARS-CoV-2 infection are defined by persistence or re-occurrence of symptoms six to 12 weeks after SARS-CoV-2 infections.

METHODS: Twice vaccinated hospital employees after mild to moderate post-vaccination SARS-CoV-2 infection completed a questionnaire on the incidence of general, respiratory, neuropsychiatric, dermatological and gastrointestinal symptoms, experienced during their acute infection and eight weeks after recovery. Post acute sequelae of SARS-CoV-2 infection were analysed in relation to socio-demographic-, health-, virus- and acute infection-related characteristics.

RESULTS: 73 participants, 25 women and 48 men with a mean age of 40.9 years, with a post-vaccination SARS-CoV-2 infection completed the survey. Out of these 93 % reported at least one symptom at time of initial SARS-CoV-2 infection, 31.5 %, predominantly women, reported post acute sequelae at least eight weeks after the acute infection stage. Fatigue, dysgeusia and dysosmia, headache or difficulty concentrating and shortness of breath during acute infection, BMI> 25 and pre-existing pulmonary disorders were associated with post acute sequelae of SARS-CoV-2 infection. Participants with initially more than five symptoms were four times more likely to report post acute sequelae.

CONCLUSION: It is suggested that the multiplicity of symptoms during acute SARS-CoV-2 infections increases the risk for post acute symptoms.}, } @article {pmid36842064, year = {2023}, author = {Guezguez, F and Romdhani, M and Boutaleb-Joutei, A and Chamari, K and Ben Saad, H}, title = {Management of long-COVID-19 patients with sleep disorders: practical advice to general practitioners.}, journal = {The Libyan journal of medicine}, volume = {18}, number = {1}, pages = {2182704}, pmid = {36842064}, issn = {1819-6357}, mesh = {Humans ; *General Practitioners ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Sleep Initiation and Maintenance Disorders/epidemiology/therapy ; Hypnotics and Sedatives ; }, abstract = {Given the high prevalence of sleep disorders (e.g. insomnia) among long-COVID-19 patients (LC19Ps), approaches to tackle these disorders should not only depend on sleep specialists, but they should also involve general practitioners (GPs). Indeed, according to the World Health Organization, GPs should be on the front line in the management of LC19Ps. However, in real practice, little data with regard to the management of LC19Ps are available for GPs, which represents an embarrassing situation. Thus, the main aim of this correspondence was to provide GPs with some advice related to the management of sleep disorders in LC19Ps. The pieces advice presented in this correspondence are related to: i) Early and accurate recognition of sleep disorders, ii) General recommendations to manage sleep disorders in LC19Ps (e.g. encouraging vaccination against the virus); and iii) Specific recommendations, such as improving sleep hygiene (patients' behavior and diet), psychological or behavioral therapies (stimulus control therapy, relaxation, sleep restriction), promising tools (heart coherence, neurofeedback), and pharmacological treatment. The authors of this correspondence deeply believe that given the undesirable side effects associated with the use of hypnotics, the pharmacological approach must only be a "last resort". The authors believe that an important percentage of pharmacological prescriptions could be avoided if more focus is put on educating GPs to provide LC19Ps with more tools to deal with sleep disorders. The pieces advice presented in this correspondence are indispensable to resume the normal life of LC19Ps and to promote their mental health recovery.}, } @article {pmid36841973, year = {2023}, author = {Yelin, D and Levi, R and Babu, C and Moshe, R and Shitenberg, D and Atamna, A and Tishler, O and Babich, T and Shapira-Lichter, I and Abecasis, D and Cohen Zubary, N and Leibovici, L and Yahav, D and Margalit, I}, title = {Assessment of Exercise Capacity of Individuals with Long COVID: A Cross-sectional Study.}, journal = {The Israel Medical Association journal : IMAJ}, volume = {25}, number = {2}, pages = {83-87}, pmid = {36841973}, issn = {1565-1088}, mesh = {Humans ; *Exercise Test ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Exercise Tolerance ; Myalgia ; *COVID-19 ; }, abstract = {BACKGROUND: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

OBJECTIVES: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

METHODS: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

RESULTS: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

CONCLUSIONS: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.}, } @article {pmid36841882, year = {2023}, author = {Schleiss, MR and Permar, SR and John, CC}, title = {What are the key pediatric public policy priorities as the COVID-19 pandemic persists?.}, journal = {Pediatric research}, volume = {93}, number = {6}, pages = {1451-1455}, pmid = {36841882}, issn = {1530-0447}, mesh = {Infant, Newborn ; Female ; Pregnancy ; Child ; Humans ; *COVID-19 ; COVID-19 Vaccines ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; Public Policy ; Vaccination ; }, abstract = {The COVID-19 pandemic is not over, and its impact is just beginning to be felt on children. COVID-19 vaccines protect both the pregnant patient and newborns, and breastfeeding provides a key component of passive protective immunity. "Long COVID" has contributed to the current crisis in pediatric mental health, and vaccines confer protection against this long-term complication of COVID-19 disease. Vaccine misinformation is not only impacting compliance with maternal and pediatric COVID-19 immunization efforts, but also other routine childhood vaccinations. As a public health priority, we must improve our response to vaccine misinformation and find novel strategies to improve vaccine compliance.}, } @article {pmid36841740, year = {2023}, author = {Bucciol, G and , and Meyts, I}, title = {Inherited and acquired errors of type I interferon immunity govern susceptibility to COVID-19 and multisystem inflammatory syndrome in children.}, journal = {The Journal of allergy and clinical immunology}, volume = {151}, number = {4}, pages = {832-840}, pmid = {36841740}, issn = {1097-6825}, support = {R01 AI088364/AI/NIAID NIH HHS/United States ; R01 AI163029/AI/NIAID NIH HHS/United States ; UL1 RR024143/RR/NCRR NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; }, mesh = {SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Male ; Young Adult ; Humans ; *Interferon Type I ; }, abstract = {Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic, global sequencing efforts have led in the field of inborn errors of immunity, and inspired particularly by previous research on life-threatening influenza, they have revealed that known and novel inborn errors affecting type I interferon immunity underlie critical COVID-19 in up to 5% of cases. In addition, neutralizing autoantibodies against type I interferons have been identified in up to 20% of patients with critical COVID-19 who are older than 80 years and 20% of fatal cases, with a higher prevalence in men and individuals older than 70 years. Also, inborn errors impairing regulation of type I interferon responses and RNA degradation have been found as causes of multisystem inflammatory syndrome in children, a life-threatening hyperinflammatory condition complicating otherwise mild initial SARS-CoV-2 infection in children and young adults. Better understanding of these immunologic mechanisms can aid in designing treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID.}, } @article {pmid36839224, year = {2023}, author = {Mey, JT and Kirwan, JP and Axelrod, CL}, title = {The Role of Nutrition in Mitigating the Effects of COVID-19 from Infection through PASC.}, journal = {Nutrients}, volume = {15}, number = {4}, pages = {}, pmid = {36839224}, issn = {2072-6643}, support = {U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Acute Disease ; Disease Progression ; Nutritional Status ; }, abstract = {The expansive and rapid spread of the SARS-CoV-2 virus has resulted in a global pandemic of COVID-19 infection and disease. Though initially perceived to be acute in nature, many patients report persistent and recurrent symptoms beyond the infectious period. Emerging as a new epidemic, "long-COVID", or post-acute sequelae of coronavirus disease (PASC), has substantially altered the lives of millions of people globally. Symptoms of both COVID-19 and PASC are individual, but share commonality to established respiratory viruses, which include but are not limited to chest pain, shortness of breath, fatigue, along with adverse metabolic and pulmonary health effects. Nutrition plays a critical role in immune function and metabolic health and thus is implicated in reducing risk or severity of symptoms for both COVID-19 and PASC. However, despite the impact of nutrition on these key physiological functions related to COVID-19 and PASC, the precise role of nutrition in COVID-19 infection and PASC onset or severity remains to be elucidated. This narrative review will discuss established and emerging nutrition approaches that may play a role in COVID-19 and PASC, with references to the established nutrition and clinical practice guidelines that should remain the primary resources for patients and practitioners.}, } @article {pmid36839188, year = {2023}, author = {La Carrubba, A and Veronese, N and Di Bella, G and Cusumano, C and Di Prazza, A and Ciriminna, S and Ganci, A and Naro, L and Dominguez, LJ and Barbagallo, M and On Behalf Of The Comepa Group, }, title = {Prognostic Value of Magnesium in COVID-19: Findings from the COMEPA Study.}, journal = {Nutrients}, volume = {15}, number = {4}, pages = {}, pmid = {36839188}, issn = {2072-6643}, mesh = {Male ; Humans ; Aged ; Female ; *COVID-19 ; Magnesium ; Prognosis ; Hospital Mortality ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; }, abstract = {Magnesium (Mg) plays a key role in infections. However, its role in coronavirus disease 2019 (COVID-19) is still underexplored, particularly in long-term sequelae. The aim of the present study was to examine the prognostic value of serum Mg levels in older people affected by COVID-19. Patients were divided into those with serum Mg levels ≤1.96 vs. >1.96 mg/dL, according to the Youden index. A total of 260 participants (mean age 65 years, 53.8% males) had valid Mg measurements. Serum Mg had a good accuracy in predicting in-hospital mortality (area under the curve = 0.83; 95% CI: 0.74-0.91). Low serum Mg at admission significantly predicted in-hospital death (HR = 1.29; 95% CI: 1.03-2.68) after adjusting for several confounders. A value of Mg ≤ 1.96 mg/dL was associated with a longer mean length of stay compared to those with a serum Mg > 1.96 (15.2 vs. 12.7 days). Low serum Mg was associated with a higher incidence of long COVID symptomatology (OR = 2.14; 95% CI: 1.30-4.31), particularly post-traumatic stress disorder (OR = 2.00; 95% CI: 1.24-16.40). In conclusion, low serum Mg levels were significant predictors of mortality, length of stay, and onset of long COVID symptoms, indicating that measuring serum Mg in COVID-19 may be helpful in the prediction of complications related to the disease.}, } @article {pmid36837480, year = {2023}, author = {Coman, AE and Ceasovschih, A and Petroaie, AD and Popa, E and Lionte, C and Bologa, C and Haliga, RE and Cosmescu, A and Slănină, AM and Bacușcă, AI and Șorodoc, V and Șorodoc, L}, title = {The Significance of Low Magnesium Levels in COVID-19 Patients.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837480}, issn = {1648-9144}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Magnesium ; Lung ; }, abstract = {Magnesium is the fourth most common mineral in the human body and the second richest intracellular cation. This element is necessary for many physiological reactions, especially in the cardiovascular and respiratory systems. COVID-19 is an infectious disease caused by SARS-CoV-2. The majority of people who become ill as a result of COVID-19 have mild-to-moderate symptoms and recover without specific treatment. Moreover, there are people who develop severe forms of COVID-19, which require highly specialized medical assistance. Magnesium deficiency may play a role in the pathophysiology of infection with SARS-CoV-2. The primary manifestation of COVID-19 remains respiratory, but the virus can spread to other organs and tissues, complicating the clinical picture and culminating in multiorgan failure. The key mechanisms involved in the disease include direct viral cytotoxicity, endothelial dysfunction, and exaggerated release of inflammatory cytokines. The aim of this review was to summarize the available data regarding the role of magnesium in COVID-19 patients and its particularities in different clinical settings.}, } @article {pmid36837463, year = {2023}, author = {Sakurada, Y and Otsuka, Y and Tokumasu, K and Sunada, N and Honda, H and Nakano, Y and Matsuda, Y and Hasegawa, T and Ochi, K and Hagiya, H and Ueda, K and Kataoka, H and Otsuka, F}, title = {Trends in Long COVID Symptoms in Japanese Teenage Patients.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837463}, issn = {1648-9144}, support = {JP22K20927//Japan Society for the Promotion of Science/ ; JP22K20927//This work was supported by JSPS KAKENHI (Y.O.) and Ryobi Teien Memory Foundation (2022) in Japan (F.O.)./ ; }, mesh = {Adult ; Child ; Adolescent ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; East Asian People ; SARS-CoV-2 ; Fatigue ; Headache ; Observational Studies as Topic ; }, abstract = {Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.}, } @article {pmid36836865, year = {2023}, author = {Paradowska-Nowakowska, E and Łoboda, D and Gołba, KS and Sarecka-Hujar, B}, title = {Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {36836865}, issn = {2075-1729}, support = {"Electrocardiology-Ochojec" Foundation//"Electrocardiology-Ochojec" Foundation/ ; }, abstract = {Symptoms of long COVID-19 syndrome (long COVID-19) are reported by 80% of convalescents up to several months after contracting the coronavirus-19 disease (COVID-19). The study aimed to assess the frequency and correlations of long COVID symptoms with sex, disease severity, time since the onset of the disease, and exercise capacity in a population of Polish convalescents hospitalized as a part of a rehabilitation program after COVID-19. The retrospective analysis was carried out based on medical records concerning reported symptoms, comorbidities, exercise capacity, fatigue and dyspnea on Borg's scale, arterial oxygen saturation (SpO2), spirometric parameters, chest X-rays/computed tomography scans, systolic pulmonary artery pressure, and left ventricular ejection fraction. The study involved 471 patients aged 63.83 ± 9.93 years who had been hospitalized 191.32 ± 75.69 days from the onset of COVID-19, of which 269 (57.1%) were women. The most common symptoms were fatigue (99.57%), dyspnea (99.36%), and myalgia (97.03%). Women reported more symptoms than men (p < 0.001) and rated their fatigue as more severe (p = 0.021). Patients with depressed moods reported more physical symptoms than others (p < 0.001). Most long COVID symptoms, including dyspnea, fatigue, and depressive symptoms, were found with the same frequency in patients 12-24 weeks and >24 weeks after recovery (p = 0.874, p = 0.400, and p = 0.320, respectively), regardless of acute COVID-19 severity (p = 0.240, p = 0.826, and p = 0.108, respectively). Dyspnea severity correlated with forced vital capacity (FVC) (r = -0.153, p = 0.005), and forced expiratory volume in one second (FEV1) (r = -0.142, p = 0.008). Fatigue severity correlated with impaired FVC and FEV1 (both r = -0.162, p = 0.003). Fatigue and dyspnea inversely correlated with the distance in a six-minute walk test (r = -0.497, p < 0.001, and r = -0.327, p < 0.001). In conclusion, in our cohort, long COVID symptoms are more common in women. Dyspnea/fatigue and depressive symptoms do not tend to subside after an average six-month recovery period. The intensity of perceived fatigue may be exaggerated by the coexistence of neuropsychiatric disorders. Increased fatigue and dyspnea correlate with impaired spirometric parameters and significantly affects convalescents' exercise capacity.}, } @article {pmid36836605, year = {2023}, author = {Zavori, L and Molnar, T and Varnai, R and Kanizsai, A and Nagy, L and Vadkerti, B and Szirmay, B and Schwarcz, A and Csecsei, P}, title = {Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836605}, issn = {2075-4426}, abstract = {Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study. We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine. In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.}, } @article {pmid36836568, year = {2023}, author = {Conti, V and Corbi, G and Sabbatino, F and De Pascale, D and Sellitto, C and Stefanelli, B and Bertini, N and De Simone, M and Liguori, L and Di Paola, I and De Bernardo, M and Tesse, A and Rosa, N and Pagliano, P and Filippelli, A}, title = {Long COVID: Clinical Framing, Biomarkers, and Therapeutic Approaches.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836568}, issn = {2075-4426}, abstract = {More than two years after the onset of the COVID-19 pandemic, healthcare providers are facing an emergency within an emergency, the so-called long COVID or post-COVID-19 syndrome (PCS). Patients diagnosed with PCS develop an extended range of persistent symptoms and/or complications from COVID-19. The risk factors and clinical manifestations are many and various. Advanced age, sex/gender, and pre-existing conditions certainly influence the pathogenesis and course of this syndrome. However, the absence of precise diagnostic and prognostic biomarkers may further complicate the clinical management of patients. This review aimed to summarize recent evidence on the factors influencing PCS, possible biomarkers, and therapeutic approaches. Older patients recovered approximately one month earlier than younger patients, with higher rates of symptoms. Fatigue during the acute phase of COVID-19 appears to be an important risk factor for symptom persistence. Female sex, older age, and active smoking are associated with a higher risk of developing PCS. The incidence of cognitive decline and the risk of death are higher in PCS patients than in controls. Complementary and alternative medicine appears to be associated with improvement in symptoms, particularly fatigue. The heterogeneous nature of post-COVID symptoms and the complexity of patients with PCS, who are often polytreated due to concomitant clinical conditions, suggest a holistic and integrated approach to provide useful guidance for the treatment and overall management of long COVID.}, } @article {pmid36836515, year = {2023}, author = {Bazdar, S and Kwee, AKAL and Houweling, L and de Wit-van Wijck, Y and Mohamed Hoesein, FAA and Downward, GS and Nossent, EJ and Maitland-van der Zee, AH and , }, title = {A Systematic Review of Chest Imaging Findings in Long COVID Patients.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836515}, issn = {2075-4426}, support = {//Health Holland/ ; //Top Sector Life Sciences & Health (LSHM20104; LSHM20068)/ ; //Novartis (Netherlands)/ ; }, abstract = {Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID. Two independent researchers extracted the data. Our search identified 3130 articles, of which 31, representing the imaging findings of 342 long COVID patients, were retained. The most common imaging modality used was computed tomography (CT) (N = 249). A total of 29 different imaging findings were reported, which were broadly categorized into interstitial (fibrotic), pleural, airway, and other parenchymal abnormalities. A direct comparison between cases, in terms of residual lesions, was available for 148 patients, of whom 66 (44.6%) had normal CT findings. Although respiratory symptoms belong to the most common symptoms in long COVID patients, this is not necessarily linked to radiologically detectable lung damage. Therefore, more research is needed on the role of the various types of lung (and other organ) damage which may or may not occur in long COVID.}, } @article {pmid36836416, year = {2023}, author = {Postolache, PA and Nechifor, A and Buculei, I and Soare, I and Mocanu, H and Petrariu, FD}, title = {Clinical Features and Paraclinical Findings in Patients with SARS CoV-2 Pneumonia and the Impact of Pulmonary Rehabilitation on the Instrumental Activities of Daily Living in POST-COVID-19 Patients.}, journal = {Journal of personalized medicine}, volume = {13}, number = {2}, pages = {}, pmid = {36836416}, issn = {2075-4426}, abstract = {The functional sequelae grouped under the name "long COVID" most often bring the patient in front of a team of specialists in pulmonary rehabilitation. The aim of this study was to evaluate clinical features and paraclinical findings in patients with SARS CoV-2 (Severe Acute Respiratory Syndrome-Corona Virus-2) pneumonia and to also evaluate the impact of rehabilitation in this category of patients. This study included 106 patients diagnosed with SARS CoV-2. The division of the patients into two groups was performed based on the presence of SAR-CoV-2 pneumonia. Clinical symptoms, biochemical parameters, and pulmonary functional and radiological examinations were recorded and analyzed. The Lawton Instrumental Activities of Daily Living (IADL) scale was applied to all patients. Patients in group I were included in the pulmonary rehabilitation program. Among demographic characteristics, age over 50 years (50.9%; p = 0.027) and the female sex (66%; p = 0.042) were risk factors for pneumonia in patients with SARS CoV-2. Over 90% of the 26 patients included in the rehabilitation program were less able to feed, bathe, dress, and walk. After 2 weeks, approximately 50% of patients were able to eat, wash, and dress. It is important to provide longer rehabilitation programs in cases of moderate, severe, and very severe COVID-19 patients, in order to significantly improve patients' participation in daily activities and their quality of life.}, } @article {pmid36836207, year = {2023}, author = {Williams, LD and Zis, P}, title = {COVID-19-Related Neuropathic Pain: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36836207}, issn = {2077-0383}, abstract = {INTRODUCTION: SARS-CoV-2, responsible for the coronavirus disease (COVID-19) pandemic, may impact other systems apart from the respiratory system, including the nervous system. In this systematic review, we aimed to establish the prevalence and determinants of neuropathic pain amongst COVID-19-infected individuals.

METHODOLOGY: A literature search in the PubMed database was performed and 11 papers were eligible for inclusion in this systematic review and meta-analysis.

RESULTS: The pooled prevalence of COVID-19-related neuropathic pain was 6.7% (95% CI: 4.7-9.5%) for hospitalised patients during the acute phase and 34.3% (95% CI: 14.3-62%) for long COVID patients. The identified risk factors for COVID-19-related neuropathic pain development included depression, COVID-19 severity and azithromycin use.

CONCLUSIONS: Neuropathic pain is a very common symptom in long COVID, indicating the urgency for further research in this direction.}, } @article {pmid36836071, year = {2023}, author = {Niebauer, JH and Binder-Rodriguez, C and Iscel, A and Schedl, S and Capelle, C and Kahr, M and Cadjo, S and Schamilow, S and Badr-Eslam, R and Lichtenauer, M and Toma, A and Zoufaly, A and Valenta, R and Hoffmann, S and Charwat-Resl, S and Krestan, C and Hitzl, W and Wenisch, C and Bonderman, D}, title = {Cardiopulmonary Long-Term Sequelae in Patients after Severe COVID-19 Disease.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36836071}, issn = {2077-0383}, abstract = {We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2-11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6-16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03-17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05-1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05-2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction.}, } @article {pmid36835863, year = {2023}, author = {Fritsche, LG and Jin, W and Admon, AJ and Mukherjee, B}, title = {Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 Infection (PASC) in a Large Academic Medical Center in the US.}, journal = {Journal of clinical medicine}, volume = {12}, number = {4}, pages = {}, pmid = {36835863}, issn = {2077-0383}, support = {K08 HL155407/HL/NHLBI NIH HHS/United States ; P30 CA046592/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by post-acute sequelae of SARS CoV-2 infection (PACS). Using electronic health record data, we aimed to characterize PASC-associated diagnoses and develop risk prediction models.

METHODS: In our cohort of 63,675 patients with a history of COVID-19, 1724 (2.7%) had a recorded PASC diagnosis. We used a case-control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into phenotype risk scores (PheRSs) and evaluated their predictive performance.

RESULTS: In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and sixty-nine phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the cohort with a history of COVID-19 with a 3.5-fold increased risk (95% CI: 2.19, 5.55) for PASC compared to the bottom 50%.

CONCLUSIONS: The uncovered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with potential for risk stratification approaches.}, } @article {pmid36835589, year = {2023}, author = {Bhatia-Dey, N and Csoka, AB and Heinbockel, T}, title = {Chemosensory Ability and Sensitivity in Health and Disease: Epigenetic Regulation and COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835589}, issn = {1422-0067}, support = {P30 AI117970/AI/NIAID NIH HHS/United States ; NSF IOS-1355034//National Science Foundation/ ; n/a//Howard University College of Medicine/ ; P30AI117970/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19/complications ; *Olfaction Disorders ; Post-Acute COVID-19 Syndrome ; Pandemics ; Epigenesis, Genetic ; }, abstract = {Throughout the animal kingdom, our two chemical senses, olfaction and gustation, are defined by two primary factors: genomic architecture of the organisms and their living environment. During the past three years of the global COVID-19 pandemic, these two sensory modalities have drawn much attention at the basic science and clinical levels because of the strong association of olfactory and gustatory dysfunction with viral infection. Loss of our sense of smell alone, or together with a loss of taste, has emerged as a reliable indicator of COVID-19 infection. Previously, similar dysfunctions have been detected in a large cohort of patients with chronic conditions. The research focus remains on understanding the persistence of olfactory and gustatory disturbances in the post-infection phase, especially in cases with long-term effect of infection (long COVID). Also, both sensory modalities show consistent age-related decline in studies aimed to understand the pathology of neurodegenerative conditions. Some studies using classical model organisms show an impact on neural structure and behavior in offspring as an outcome of parental olfactory experience. The methylation status of specific odorant receptors, activated in parents, is passed on to the offspring. Furthermore, experimental evidence indicates an inverse correlation of gustatory and olfactory abilities with obesity. Such diverse lines of evidence emerging from basic and clinical research studies indicate a complex interplay of genetic factors, evolutionary forces, and epigenetic alterations. Environmental factors that regulate gustation and olfaction could induce epigenetic modulation. However, in turn, such modulation leads to variable effects depending on genetic makeup and physiological status. Therefore, a layered regulatory hierarchy remains active and is passed on to multiple generations. In the present review, we attempt to understand the experimental evidence that indicates variable regulatory mechanisms through multilayered and cross-reacting pathways. Our analytical approach will add to enhancement of prevailing therapeutic interventions and bring to the forefront the significance of chemosensory modalities for the evaluation and maintenance of long-term health.}, } @article {pmid36835341, year = {2023}, author = {Brogna, C and Costanzo, V and Brogna, B and Bisaccia, DR and Brogna, G and Giuliano, M and Montano, L and Viduto, V and Cristoni, S and Fabrowski, M and Piscopo, M}, title = {Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835341}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2/genetics ; *COVID-19 ; RNA ; *Bacteriophages/genetics ; Amino Acids ; Proteomics ; *Viruses/genetics ; Microscopy, Fluorescence ; }, abstract = {SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients' blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.}, } @article {pmid36834984, year = {2023}, author = {Reyes-Long, S and Cortés-Altamirano, JL and Bandala, C and Avendaño-Ortiz, K and Bonilla-Jaime, H and Bueno-Nava, A and Ávila-Luna, A and Sánchez-Aparicio, P and Clavijo-Cornejo, D and Dotor-LLerena, AL and Cabrera-Ruiz, E and Alfaro-Rodríguez, A}, title = {Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36834984}, issn = {1422-0067}, mesh = {Humans ; *Chronic Pain/genetics ; *COVID-19/complications/genetics ; *MicroRNAs/genetics ; *Post-Acute COVID-19 Syndrome/genetics ; }, abstract = {The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.}, } @article {pmid36834176, year = {2023}, author = {Chandan, JS and Brown, KR and Simms-Williams, N and Bashir, NZ and Camaradou, J and Heining, D and Turner, GM and Rivera, SC and Hotham, R and Minhas, S and Nirantharakumar, K and Sivan, M and Khunti, K and Raindi, D and Marwaha, S and Hughes, SE and McMullan, C and Marshall, T and Calvert, MJ and Haroon, S and Aiyegbusi, OL and , }, title = {Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36834176}, issn = {1660-4601}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Mental Health ; }, abstract = {BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.

METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.

FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.

REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.}, } @article {pmid36833793, year = {2023}, author = {Duñabeitia, JA and Mera, F and Baro, Ó and Jadad-Garcia, T and Jadad, AR}, title = {Personalized Computerized Training for Cognitive Dysfunction after COVID-19: A Before-and-After Feasibility Pilot Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {4}, pages = {}, pmid = {36833793}, issn = {1660-4601}, mesh = {Adult ; Humans ; Pilot Projects ; Feasibility Studies ; *COVID-19 ; *Cognitive Dysfunction/psychology ; Cognition ; Post-Acute COVID-19 Syndrome ; }, abstract = {The current pilot study was set to evaluate the feasibility and potential benefit of a personalized computerized cognitive training (CCT) intervention to improve cognitive function among people living with post-acute sequelae of COVID-19 (PASC). Seventy three adults who self-reported cognitive dysfunction more than 3 months after a diagnosis of COVID-19 took part in an 8-week training study. Participants' general cognitive function was assessed before they completed as many cognitive daily training sessions as they wished during an 8-week period, using a personalized CCT application at home. At the end of this period, participants repeated the general cognitive function assessment. The differences between the scores at 8 weeks and baseline in five cognitive domains (attention, memory, coordination, perception, reasoning), complemented with analyses of the changes based on the participants' age, training time, self-reported health level at baseline and time since the initial COVID-19 infection. Participants had significant cognitive dysfunction and self-reported negative health levels at baseline. Most of the participants obtained higher scores after CCT in each of the domains as compared with baseline. The magnitude of this score increase was high across domains. It is concluded that a self-administered CCT based on gamified cognitive tasks could be an effective way to ameliorate cognitive dysfunction in persons with PASC. The ClinicalTrials.gov identifier is NCT05571852.}, } @article {pmid36832543, year = {2023}, author = {Skinner, JP and Moran, LV}, title = {Persistent effects of COVID-19 in patients hospitalized during the first wave of the pandemic: The impact of persistent fatigue on quality of life in a cross-sectional study.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28491}, doi = {10.1002/jmv.28491}, pmid = {36832543}, issn = {1096-9071}, support = {R01 MH122427/MH/NIMH NIH HHS/United States ; }, mesh = {Male ; Humans ; Adult ; Middle Aged ; Aged ; Female ; *COVID-19 ; Quality of Life ; Cross-Sectional Studies ; Pandemics ; Post-Acute COVID-19 Syndrome ; Fatigue ; Dyspnea ; }, abstract = {COVID-19 can affect physical and mental health long after acute infection. In this descriptive study, 48 individuals hospitalized for COVID-19 between April and May 2020 were interviewed regarding their experience with COVID-19 after hospitalization. The mean age of participants was 51.1 (±11.91) years (range 25-65 years) and 26 (54.2%) were men. Individuals had a mean of 1.2 (±0.94) comorbidities associated with more severe COVID-19, with hypertension (37.5%) being most common. Nineteen (39.6%) individuals required treatment in the intensive care unit. Participants were interviewed a median time of 553 days (IQR, 405.5-589.0) after discharge from the hospital. Thirty-seven (77.1%) individuals had 5 or more persistent symptoms at time of interview with only 3 (6.3%) experiencing none. The most reported persistent symptoms were fatigue (79.2%), difficulty breathing (68.8%), and muscle weakness (60.4%). Poor quality of life was experienced by 39 (81.3%) participants and 8 (16.7%) had a posttraumatic stress disorder (PTSD) score within the clinical range for diagnosis. For multivariable analyses, persistent fatigue was significantly predicted by number of symptoms during acute COVID-19 (t = 4.4, p < 0.001). Number of symptoms during acute COVID-19 was also significantly associated with persistent dyspnea (t = 3.4, p = 0.002). Higher scores on the Chalder fatigue scale after COVID-19 was significantly associated with poor quality of life (t = 2.6, p = 0.01) and PTSD symptomatology (t = 2.9, p = 0.008). More research is needed to highlight the wide range of resources those suffering from Long COVID require long after discharge.}, } @article {pmid36832445, year = {2023}, author = {Buchhorn, R}, title = {Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID.}, journal = {Children (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {36832445}, issn = {2227-9067}, abstract = {BACKGROUND: Dysautonomia seems to be important for the pathophysiology of psychosomatic diseases and, more recently, for long COVID. This concept may explain the clinical symptoms and could help open new therapeutic approaches.

METHODS: We compared our data from an analysis of heart rate variability (HRV) in an active standing test in 28 adolescents who had developed an inappropriate sinus tachycardia (IST, n = 13) or postural orthostatic tachycardia syndrome (POTS, n = 15) after contracting COVID-19 disease and/or vaccination with 64 adolescents from our database who developed dysautonomia due to psychosomatic diseases prior to the COVID-19 pandemic. We prove the effects of our treatment: omega-3 fatty acid supplementation (O3-FA, n = 18) in addition to propranolol (low dose, up to 20-20-0 mg, n = 32) or ivabradine 5-5-0 mg (n = 17) on heart rate regulation and heart rate variability (HRV).

RESULTS: The HRV data were not different between the adolescents with SARS-CoV-2-related disorders and the adolescents with dysautonomia prior to the pandemic. The heart rate increases in children with POTS while standing were significantly lower after low-dose propranolol (27.2 ± 17.4 bpm***), ivabradine (23.6 ± 8.12 bpm*), and O-3-FA (25.6 ± 8.4 bpm*). The heart rate in children with IST while lying/standing was significantly lower after propranolol (81.6 ± 10.1 bpm**/101.8 ± 18.8***), ivabradine (84.2 ± 8.4 bpm***/105.4 ± 14.6**), and O-3-FA (88.6 ± 7.9 bpm*/112.1/14.9*).

CONCLUSIONS: The HRV data of adolescents with dysautonomia after COVID-19 disease/vaccination are not significantly different from a historical control of adolescents with dysautonomia due to psychosomatic diseases prior to the pandemic. Low-dose propranolol > ivabradine > omega-3 fatty acids significantly decrease elevated heart rates in patients with IST and the heart rate increases in patients with POTS and may be beneficial in these children with dysautonomia.}, } @article {pmid36832180, year = {2023}, author = {Lavi, Y and Vojdani, A and Halpert, G and Sharif, K and Ostrinski, Y and Zyskind, I and Lattin, MT and Zimmerman, J and Silverberg, JI and Rosenberg, AZ and Shoenfeld, Y and Amital, H}, title = {Dysregulated Levels of Circulating Autoantibodies against Neuronal and Nervous System Autoantigens in COVID-19 Patients.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {36832180}, issn = {2075-4418}, support = {0000//Yaron and Gila Shemie Foundation/ ; }, abstract = {BACKGROUND: COVID-19 is a heterogenous disease resulting in long-term sequela in predisposed individuals. It is not uncommon that recovering patients endure non-respiratory ill-defined manifestations, including anosmia, and neurological and cognitive deficit persisting beyond recovery-a constellation of conditions that are grouped under the umbrella of long-term COVID-19 syndrome. Association between COVID-19 and autoimmune responses in predisposed individuals was shown in several studies.

AIM AND METHODS: To investigate autoimmune responses against neuronal and CNS autoantigens in SARS-CoV-2-infected patients, we performed a cross-sectional study with 246 participants, including 169 COVID-19 patients and 77 controls. Levels of antibodies against the acetylcholine receptor, glutamate receptor, amyloid β peptide, alpha-synucleins, dopamine 1 receptor, dopamine 2 receptor, tau protein, GAD-65, N-methyl D-aspartate (NMDA) receptor, BDNF, cerebellar, ganglioside, myelin basic protein, myelin oligodendrocyte glycoprotein, S100-B, glial fibrillary acidic protein, and enteric nerve were measured using an Enzyme-Linked Immunosorbent Assay (ELISA). Circulating levels of autoantibodies were compared between healthy controls and COVID-19 patients and then classified by disease severity (mild [n = 74], severe [n = 65], and requiring supplemental oxygen [n = 32]).

RESULTS: COVID-19 patients were found to have dysregulated autoantibody levels correlating with the disease severity, e.g., IgG to dopamine 1 receptor, NMDA receptors, brain-derived neurotrophic factor, and myelin oligodendrocyte glycoprotein. Elevated levels of IgA autoantibodies against amyloid β peptide, acetylcholine receptor, dopamine 2 receptor, myelin basic protein, and α-synuclein were detected in COVID-19 patients compared with healthy controls. Lower IgA autoantibody levels against NMDA receptors, and IgG autoantibodies against glutamic acid decarboxylase 65, amyloid β peptide, tau protein, enteric nerve, and S100-B were detected in COVID-19 patients versus healthy controls. Some of these antibodies have known clinical correlations with symptoms commonly reported in the long COVID-19 syndrome.

CONCLUSIONS: Overall, our study shows a widespread dysregulation in the titer of various autoantibodies against neuronal and CNS-related autoantigens in convalescent COVID-19 patients. Further research is needed to provide insight into the association between these neuronal autoantibodies and the enigmatic neurological and psychological symptoms reported in COVID-19 patients.}, } @article {pmid36831611, year = {2023}, author = {Lasagna, A and Albi, G and Figini, S and Basile, S and Sacchi, P and Bruno, R and Pedrazzoli, P}, title = {Long-COVID in Patients with Cancer Previously Treated with Early Anti-SARS-CoV-2 Therapies in an Out-of-Hospital Setting: A Single-Center Experience.}, journal = {Cancers}, volume = {15}, number = {4}, pages = {}, pmid = {36831611}, issn = {2072-6694}, support = {grant no 08067620//Policlinico San Matteo Fondazione/ ; }, abstract = {The incidence of long COVID in a cohort of patients with cancer with or without previous treatment with early therapies anti-SARS-CoV-2 in an out-of-hospital setting have to be elucidated. We prospectively enrolled all patients treated for a solid tumor at the department of Medical Oncology of the Fondazione IRCCS Policlinico San Matteo with a positive SARS-CoV-2 antigen or polymerase chain reaction test from January to September 2022 (Omicron surge). Ninety-seven patients answered the survey questions by telephone at least 12 weeks after COVID-19 diagnosis in order to evaluate the incidence of long COVID symptoms. Only twelve patients (12.4%) reported long COVID. No significant difference between early therapies anti-SARS-CoV-2 31 and long COVID (p = 0.443) was seen. The female sex (p = 0.024) and diabetes mellitus (p = 0.014) are significantly associated with long COVID. No statistically significant difference between the two groups (Long COVID vs. No Long COVID) according to the time to nasal swab viral clearance (p = 0.078). The overlap between the symptoms related to the oncological disease/oncological treatment and the symptoms of long COVID is one of the main future challenges that oncologists will have to manage.}, } @article {pmid36830913, year = {2023}, author = {Ong, IZ and Kolson, DL and Schindler, MK}, title = {Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC).}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36830913}, issn = {2227-9059}, abstract = {With a growing number of patients entering the recovery phase following infection with SARS-CoV-2, understanding the long-term neurological consequences of the disease is important to their care. The neurological complications of post-acute sequelae of SARS-CoV-2 infection (NC-PASC) represent a myriad of symptoms including headaches, brain fog, numbness/tingling, and other neurological symptoms that many people report long after their acute infection has resolved. Emerging reports are being published concerning COVID-19 and its chronic effects, yet limited knowledge of disease mechanisms has challenged therapeutic efforts. To address these issues, we review broadly the literature spanning 2020-2022 concerning the proposed mechanisms underlying NC-PASC, outline the long-term neurological sequelae associated with COVID-19, and discuss potential clinical interventions.}, } @article {pmid36830790, year = {2023}, author = {Tian, J and Kaufman, DL}, title = {The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19.}, journal = {Biomedicines}, volume = {11}, number = {2}, pages = {}, pmid = {36830790}, issn = {2227-9059}, support = {UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {GABA and GABAA-receptors (GABAA-Rs) play major roles in neurodevelopment and neurotransmission in the central nervous system (CNS). There has been a growing appreciation that GABAA-Rs are also present on most immune cells. Studies in the fields of autoimmune disease, cancer, parasitology, and virology have observed that GABA-R ligands have anti-inflammatory actions on T cells and antigen-presenting cells (APCs), while also enhancing regulatory T cell (Treg) responses and shifting APCs toward anti-inflammatory phenotypes. These actions have enabled GABAA-R ligands to ameliorate autoimmune diseases, such as type 1 diabetes (T1D), multiple sclerosis (MS), and rheumatoid arthritis, as well as type 2 diabetes (T2D)-associated inflammation in preclinical models. Conversely, antagonism of GABAA-R activity promotes the pro-inflammatory responses of T cells and APCs, enhancing anti-tumor responses and reducing tumor burden in models of solid tumors. Lung epithelial cells also express GABA-Rs, whose activation helps maintain fluid homeostasis and promote recovery from injury. The ability of GABAA-R agonists to limit both excessive immune responses and lung epithelial cell injury may underlie recent findings that GABAA-R agonists reduce the severity of disease in mice infected with highly lethal coronaviruses (SARS-CoV-2 and MHV-1). These observations suggest that GABAA-R agonists may provide off-the-shelf therapies for COVID-19 caused by new SARS-CoV-2 variants, as well as novel beta-coronaviruses, which evade vaccine-induced immune responses and antiviral medications. We review these findings and further advance the notions that (1) immune cells possess GABAA-Rs to limit inflammation in the CNS, and (2) this natural "braking system" on inflammatory responses may be pharmacologically engaged to slow the progression of autoimmune diseases, reduce the severity of COVID-19, and perhaps limit neuroinflammation associated with long COVID.}, } @article {pmid36829952, year = {2023}, author = {Akanchise, T and Angelova, A}, title = {Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36829952}, issn = {2076-3921}, abstract = {Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.}, } @article {pmid36829885, year = {2023}, author = {Jankauskas, SS and Kansakar, U and Sardu, C and Varzideh, F and Avvisato, R and Wang, X and Matarese, A and Marfella, R and Ziosi, M and Gambardella, J and Santulli, G}, title = {COVID-19 Causes Ferroptosis and Oxidative Stress in Human Endothelial Cells.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {36829885}, issn = {2076-3921}, support = {R01 HL164772/HL/NHLBI NIH HHS/United States ; R01 DK123259/DK/NIDDK NIH HHS/United States ; R01 DK033823/DK/NIDDK NIH HHS/United States ; R01 HL159062/HL/NHLBI NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; R01 HL146691/HL/NHLBI NIH HHS/United States ; T32 HL144456/HL/NHLBI NIH HHS/United States ; }, abstract = {Oxidative stress and endothelial dysfunction have been shown to play crucial roles in the pathophysiology of COVID-19 (coronavirus disease 2019). On these grounds, we sought to investigate the impact of COVID-19 on lipid peroxidation and ferroptosis in human endothelial cells. We hypothesized that oxidative stress and lipid peroxidation induced by COVID-19 in endothelial cells could be linked to the disease outcome. Thus, we collected serum from COVID-19 patients on hospital admission, and we incubated these sera with human endothelial cells, comparing the effects on the generation of reactive oxygen species (ROS) and lipid peroxidation between patients who survived and patients who did not survive. We found that the serum from non-survivors significantly increased lipid peroxidation. Moreover, serum from non-survivors markedly regulated the expression levels of the main markers of ferroptosis, including GPX4, SLC7A11, FTH1, and SAT1, a response that was rescued by silencing TNFR1 on endothelial cells. Taken together, our data indicate that serum from patients who did not survive COVID-19 triggers lipid peroxidation in human endothelial cells.}, } @article {pmid36828639, year = {2024}, author = {Mazibas, H and Speybroeck, N and Dhondt, E and Lambrecht, S and Goorts, K}, title = {Long COVID in the Belgian Defence forces: prevalence, risk factors and impact on quality of daily functioning.}, journal = {BMJ military health}, volume = {170}, number = {e2}, pages = {e172-e179}, doi = {10.1136/military-2022-002280}, pmid = {36828639}, issn = {2633-3775}, mesh = {Humans ; Belgium/epidemiology ; Male ; *COVID-19/epidemiology/psychology ; *Quality of Life/psychology ; Risk Factors ; Adult ; Female ; Prevalence ; *Post-Acute COVID-19 Syndrome ; *Military Personnel/statistics & numerical data/psychology ; Surveys and Questionnaires ; SARS-CoV-2 ; Middle Aged ; Activities of Daily Living ; }, abstract = {INTRODUCTION: Long COVID (LC) is a medical condition first described and documented through anecdotes on social media by patients prior to being recognised by WHO as a disease. Although >50 prolonged symptoms of LC have been described, it remains a diagnostic challenge for military providers and therefore threatens operational readiness.

METHODS: On 9 September 2021, an online survey was emailed to 2192 Belgian Defence personnel who had previously tested PCR positive for SARS-CoV-2 between 17 August 2020 and 31 May 2021. A total of 718 validated responses were received.Descriptive analyses determined the prevalence of LC and 10 most common symptoms and their duration following infection. In the explanatory analyses, risk factors related to LC were identified. To establish the health-related impact of LC on quality of life (HRQoL), we used the results from the EuroQol 5 Dimension 5 Level questionnaire.

RESULTS: The most frequent symptoms that were reported for >3 months were fatigue, lack of energy and breathing difficulties.47.35% of the respondents reported at least one persistent symptom, while 21.87% reported more than 3 symptoms lasting for at least 3 months after the initial COVID-19 infection. Most patients with LC suffered from symptoms of a neuropsychiatric nature (71.76%).LC was significantly associated with obesity; pre-existing respiratory disease and blood or immune disorders. Physical activity of >3 hours per week halved the risk of LC.The total QoL is reduced in patients with LC. Considering the five dimensions of the questionnaire, only the self-care dimension was not influenced by the presence of LC.

CONCLUSIONS: Almost half of Belgian Defence personnel developed LC after a confirmed COVID-19 infection, similar to numbers found in the Belgian population. Patients with LC would likely benefit from a multidisciplinary rehabilitation approach that addresses shortness of breath, fatigue and mood disturbance.}, } @article {pmid36828559, year = {2023}, author = {Espinosa-Gonzalez, AB and Master, H and Gall, N and Halpin, S and Rogers, N and Greenhalgh, T}, title = {Orthostatic tachycardia after covid-19.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {e073488}, doi = {10.1136/bmj-2022-073488}, pmid = {36828559}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; *Postural Orthostatic Tachycardia Syndrome ; Posture ; *Primary Dysautonomias ; Tachycardia ; }, } @article {pmid36828209, year = {2025}, author = {Seeley, MC and Hooper, M and Tan, J and Wells, R and Gallagher, C and Lau, DH}, title = {Plasma Exchange Improves Cognitive Function in Long-COVID-Related Postural Orthostatic Tachycardia Syndrome and Autoimmune Neurological Dysfunction.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {153-154}, doi = {10.1016/j.amjmed.2023.01.043}, pmid = {36828209}, issn = {1555-7162}, } @article {pmid36828133, year = {2023}, author = {Strawn, JR and Mills, JA and Schroeder, HK and Neptune, ZA and Specht, A and Keeshin, SW}, title = {The Impact of COVID-19 Infection and Characterization of Long COVID in Adolescents With Anxiety Disorders: A Prospective Longitudinal Study.}, journal = {Journal of the American Academy of Child and Adolescent Psychiatry}, volume = {62}, number = {7}, pages = {707-709}, pmid = {36828133}, issn = {1527-5418}, support = {R01 HD098757/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Humans ; Child ; *COVID-19 ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; SARS-CoV-2 ; Anxiety Disorders/psychology ; Anxiety/psychology ; Depression/psychology ; }, abstract = {While the coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted pediatric mental health, the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on youth with anxiety disorders has not been prospectively examined. Further, there are limited prospective data on post-acute sequelae COVID-19, including symptoms that constitute the long COVID neuropsychiatric syndrome. In December 2019, we began a longitudinal study of adolescents aged 12-17 years with DSM-5 primary anxiety disorders treated with either duloxetine or escitalopram. Assessments included all items from the Generalized Anxiety Disorder-7 (GAD-7) and Quick Inventory of Depressive Symptomatology (QIDS) scales at each week and a weekly clinician-rated Clinical Global Impressions-Severity (CGI-S) scale. We examined the longitudinal course of anxiety, including following laboratory-confirmed SARS-CoV-2 infection in affected adolescents. This prospective study of the longitudinal impact of COVID-19 in pediatric anxiety disorders reveals that COVID-19 is associated with worsening anxiety symptoms and a disquieting 33% worsening in syndromic severity. Further, these data raise the possibility that, in anxious youth, COVID-19 is associated with a surfeit of neuropsychiatric symptoms.}, } @article {pmid36827994, year = {2023}, author = {Gaspar, P and Dias, M and Parreira, I and Gonçalves, HD and Parlato, F and Maione, V and Atalaia Barbacena, H and Carreiro, C and Duarte, L}, title = {Predictors of Long-COVID-19 and its Impact on Quality of Life: Longitudinal Analysis at 3, 6 and 9 Months after Discharge from a Portuguese Centre.}, journal = {Acta medica portuguesa}, volume = {36}, number = {10}, pages = {647-660}, doi = {10.20344/amp.19047}, pmid = {36827994}, issn = {1646-0758}, mesh = {Pregnancy ; Humans ; Male ; Female ; Middle Aged ; *Quality of Life ; Patient Discharge ; Longitudinal Studies ; Portugal/epidemiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Surveys and Questionnaires ; }, abstract = {INTRODUCTION: Long-COVID-19 impacts health-related quality of life (HR-QoL) but data is scarce. The aim of this study was to describe and prospectively assess the prevalence and risk factors for long-COVID-19 after hospital discharge, and to evaluate its impact on patient HR-QoL.

MATERIAL AND METHODS: Single-centre longitudinal study including all COVID-19 patients discharged between December 2020 and February 2021. Patients were contacted remotely at three, six and nine months. Data were collected as follows: 1) Long-COVID-19 symptoms were self-reported; 2) HRQoL were assessed using the 3-level EuroQoL-5D (EQ-5D-3L) questionnaire. Pregnant women, demented, bedridden, and non-Portuguese-speaking patients were excluded.

RESULTS: The three-, six- and nine-month assessments were completed by 152, 117 and 110 patients (median age: 61 years; male sex: 56.6%). Long-COVID-19 (≥ 1 symptom) was reported by 66.5%, 62.4% and 53.6% of patients and HR-QoL assessment showed impairment of at least some domain in 65.8%, 69.2% and 55.4% of patients at three, six and nine months, respectively. Fatigue was the most common long-COVID-19 symptom. Anxiety/depression domain was the most frequently affected in all three time-points, peaking at six months (39%), followed by pain/discomfort and mobility domains. Long-COVID-19 was associated with the impairment of all EQ-5D-3L domains except for self-care domain at each time-point. Neither intensive care unit admission nor disease severity were associated with long-COVID-19 nor with impairment of any EQ-5D-3L domain. After adjusting for sex, age, frailty status, and comorbid conditions, long-COVID-19 remained significantly associated with HR-QoL impairment at three (OR 4.27, 95% CI 1.92 - 9.52, p < 0.001), six (OR 3.46, 95% CI 1.40 - 8.57, p = 0.007) and nine months (OR 4.13, 95% CI 1.62 - 10.55, p = 0.003) after hospital discharge. In a longitudinal analysis, patients reporting long-COVID-19 at three months had an EQ-5D-3L index value decreased by 0.14 per visit (p < 0.001) compared to those without long-COVID-19 and both groups had a non-significant change in mean EQ-5D-3L index over the nine-month period (time-point assessment, Z = 0.91, p = 0.364).

CONCLUSION: Clinical sequelae associated with long-COVID-19 can persist for at least nine months after hospital discharge in most patients and can impair long-term HR-QoL in more than half of patients regardless of disease severity, and clinicodemographic characteristics.}, } @article {pmid36825730, year = {2023}, author = {Pakkir Maideen, NM and Hassan Jumale, A and Ramadan Barakat, I and Khalifa Albasti, A}, title = {Potential of Black Seeds (Nigella sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms - An Insight.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {4}, pages = {e230223213955}, doi = {10.2174/1871526523666230223112045}, pmid = {36825730}, issn = {2212-3989}, mesh = {Animals ; Humans ; Plant Extracts/pharmacology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Nigella sativa ; Seeds ; }, abstract = {BACKGROUND: Some individuals may experience symptoms persisting for many months after the recovery from COVID-19 and patients with Long COVID are managed mainly with symptomatic treatment and supportive care.

OBJECTIVE: This review article focuses on the beneficial effects of black seeds (Nigella sativa) in the management of long COVID and persistent COVID symptoms.

METHODS: The literature was searched in databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, Embase, and reference lists to identify studies, which evaluated various effects of black seeds (N. sativa) related to signs and symptoms of long COVID.

RESULTS: Black seeds (N. sativa) have shown potential anti-COVID, antiviral, anti-inflammatory, antioxidant, immunomodulatory, antihypertensive, anti-obesity, antidiabetic, antihyperlipidemic, and antiasthmatic properties in various clinical, animal, in vitro, in vivo, and in silico studies, which would help the patients recovered from COVID to mitigate Long COVID complications.

CONCLUSION: Patients experiencing Long COVID may use black seeds (N. sativa) as adjunctive therapy in combination with symptomatic treatment and supportive care to prevent further deterioration and hospitalization. The safety and efficacy of N. sativa in patients with Long-COVID would further be established by future randomized controlled clinical trials.}, } @article {pmid36824451, year = {2023}, author = {Xiang, M and Wu, X and Jing, H and Novakovic, VA and Shi, J}, title = {The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury.}, journal = {Frontiers in cardiovascular medicine}, volume = {10}, number = {}, pages = {1062491}, pmid = {36824451}, issn = {2297-055X}, abstract = {The role of hypoxia, vascular endothelial injury, and thrombotic inflammation in worsening COVID-19 symptoms has been generally recognized. Damaged vascular endothelium plays a crucial role in forming in situ thrombosis, pulmonary dysfunction, and hypoxemia. Thrombotic inflammation can further aggravate local vascular endothelial injury and affect ventilation and blood flow ratio. According to the results of many studies, obesity is an independent risk factor for a variety of severe respiratory diseases and contributes to high mechanical ventilation rate, high mortality, and slow recovery in COVID-19 patients. This review will explore the mechanisms by which obesity may aggravate the acute phase of COVID-19 and delay long COVID recovery by affecting hypoxia, vascular endothelial injury, and thrombotic inflammation. A systematic search of PubMed database was conducted for papers published since January 2020, using the medical subject headings of "COVID-19" and "long COVID" combined with the following keywords: "obesity," "thrombosis," "endothelial injury," "inflammation," "hypoxia," "treatment," and "anticoagulation." In patients with obesity, the accumulation of central fat restricts the expansion of alveoli, exacerbating the pulmonary dysfunction caused by SARS-CoV-2 invasion, inflammatory damage, and lung edema. Abnormal fat secretion and immune impairment further aggravate the original tissue damage and inflammation diffusion. Obesity weakens baseline vascular endothelium function leading to an early injury and pre-thrombotic state after infection. Enhanced procoagulant activity and microthrombi promote early obstruction of the vascular. Obesity also prolongs the duration of symptoms and increases the risk of sequelae after hospital discharge. Persistent viral presence, long-term inflammation, microclots, and hypoxia may contribute to the development of persistent symptoms, suggesting that patients with obesity are uniquely susceptible to long COVID. Early interventions, including supplemental oxygen, comprehensive antithrombotic therapy, and anti-inflammatory drugs, show effectiveness in many studies in the prevention of serious hypoxia, thromboembolic events, and systemic inflammation, and are therefore recommended to reduce intensive care unit admission, mortality, and sequelae.}, } @article {pmid36824312, year = {2023}, author = {Méndez-García, LA and Carrillo-Ruiz, JD and Solleiro-Villavicencio, H}, title = {Editorial: Short and long-term sequelae within the central nervous system due to COVID-19.}, journal = {Frontiers in cellular neuroscience}, volume = {17}, number = {}, pages = {1146839}, pmid = {36824312}, issn = {1662-5102}, } @article {pmid36822995, year = {2023}, author = {Ross, J}, title = {Long COVID: A Concern for Health Care Providers Into 2023 and Beyond.}, journal = {Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses}, volume = {38}, number = {2}, pages = {355-356}, doi = {10.1016/j.jopan.2023.01.007}, pmid = {36822995}, issn = {1532-8473}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Health Personnel ; }, } @article {pmid36822818, year = {2023}, author = {Roca-Fernandez, A and Wamil, M and Telford, A and Carapella, V and Borlotti, A and Monteiro, D and Thomaides-Brears, H and Kelly, M and Dennis, A and Banerjee, R and Robson, M and Brady, M and Lip, GYH and Bull, S and Heightman, M and Ntusi, N and Banerjee, A}, title = {Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection.}, journal = {Open heart}, volume = {10}, number = {1}, pages = {}, pmid = {36822818}, issn = {2053-3624}, mesh = {Humans ; Stroke Volume ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Quality of Life ; Predictive Value of Tests ; SARS-CoV-2 ; Ventricular Function, Right ; }, abstract = {BACKGROUND: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID.

OBJECTIVES: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection.

METHODS: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls.

RESULTS: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months.

CONCLUSION: CMR abnormalities (left entricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.

TRIAL REGISTRATION NUMBER: NCT04369807.}, } @article {pmid36822507, year = {2023}, author = {Mejias, A and Schuchard, J and Rao, S and Bennett, TD and Jhaveri, R and Thacker, D and Bailey, LC and Christakis, DA and Pajor, NM and Razzaghi, H and Forrest, CB and Lee, GM}, title = {Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.}, journal = {The Journal of pediatrics}, volume = {257}, number = {}, pages = {113358}, pmid = {36822507}, issn = {1097-6833}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Antibodies, Viral ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; *COVID-19/complications/diagnosis ; Humans ; Electronic Health Records ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; Disease Progression ; Cohort Studies ; }, abstract = {Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.}, } @article {pmid36818469, year = {2022}, author = {Thompson, JS and Thornton, AC and Ainger, T and Garvy, BA}, title = {Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1033651}, pmid = {36818469}, issn = {1664-3224}, mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; *COVID-19/etiology ; Post-Acute COVID-19 Syndrome ; Lung ; Immunoglobulins ; Immunization, Passive/adverse effects ; }, abstract = {INTRODUCTION: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.

METHODS: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.

RESULTS: The patients' ages ranged from 34 to 79 years-with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.

CONCLUSION: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.}, } @article {pmid36818111, year = {2023}, author = {Llana, T and Mendez, M and Garces-Arilla, S and Hidalgo, V and Mendez-Lopez, M and Juan, MC}, title = {Association between olfactory dysfunction and mood disturbances with objective and subjective cognitive deficits in long-COVID.}, journal = {Frontiers in psychology}, volume = {14}, number = {}, pages = {1076743}, pmid = {36818111}, issn = {1664-1078}, abstract = {BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) has been associated with olfactory dysfunction. The persistent symptoms of anosmia or hyposmia were associated in previous studies with the development of memory impairment and mood disturbances. We aimed to investigate the association between the chronicity of reported olfactory dysfunction and subjective and objective cognitive performance in long-COVID patients and to explore whether their emotional symptoms are related to their cognition.

METHODS: One hundred twenty-eight long-COVID participants were recruited. Reported symptomatology, subjective memory complaints, anxiety and depression symptomatology, and trait-anxiety were assessed. Subjective memory complaints and mood disturbances were compared among groups of participants with olfactory dysfunction as an acute (AOD), persistent (POD), or nonexistent (NOD) symptom. Seventy-six of the volunteers also participated in a face-to-face session to assess their objective performance on tests of general cognitive function and verbal declarative memory. Objective cognitive performance and mood disturbances were compared among the AOD, POD, and NOD groups.

RESULTS: The subjective memory complaints and the anxiety and depression symptoms were similar among the groups, but the score in general cognitive function was lower in the participants with symptoms of acute olfactory dysfunction than in those with no olfactory symptoms at any time. Participants' memory complaints were positively related to their emotional symptoms. The relationship between depressive symptomatology and memory complaints interacted with the olfactory dysfunction, as it only occurred in the participants without symptoms of olfactory dysfunction. Depressive symptomatology and acute olfactory symptoms were negatively associated with general cognitive function and delayed memory performance. The months elapsed from diagnosis to assessment also predicted delayed memory performance. Anxious symptomatology was negatively associated with the immediate ability to recall verbal information in participants who did not present olfactory dysfunction in the acute phase of the infection.

CONCLUSION: Olfactory dysfunction in the acute phase of the infection by COVID-19 is related to cognitive deficits in objective tests, and mood disturbances are associated with self-reported and objective memory. These findings may contribute to further understanding the neuropsychological and emotional aspects of long-COVID.}, } @article {pmid36817925, year = {2023}, author = {Ahmad, I and Edin, A and Granvik, C and Kumm Persson, L and Tevell, S and Månsson, E and Magnuson, A and Marklund, I and Persson, IL and Kauppi, A and Ahlm, C and Forsell, MNE and Sundh, J and Lange, A and Cajander, S and Normark, J}, title = {High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1104267}, pmid = {36817925}, issn = {2296-2565}, mesh = {Humans ; *COVID-19 ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; Prevalence ; Prospective Studies ; Quality of Life ; Self Report ; }, abstract = {BACKGROUND: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae.

METHODS: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression.

RESULTS: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+.

CONCLUSION: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.}, } @article {pmid36815864, year = {2023}, author = {Velichkovsky, BB and Razvaliaeva, AY and Khlebnikova, AA and Manukyan, PA and Kasatkin, VN and Barmin, AV}, title = {Systematic Review and Meta-Analysis of Clinically Relevant Executive Functions Tests Performance after COVID-19.}, journal = {Behavioural neurology}, volume = {2023}, number = {}, pages = {1094267}, pmid = {36815864}, issn = {1875-8584}, mesh = {Humans ; Executive Function ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cognition ; *Cognition Disorders/psychology ; }, abstract = {It is widely known that COVID-19 has a number of prolonged effects on general health, wellbeing, and cognitive functioning. However, studies using differentiated performance measures of cognitive functions are still not widely spread making it hard to assess the exact functions that get impaired. Taking into account the similarities between post-COVID 'brain fog' and chemofog, we hypothesized that executive functions (EF) would be impaired. Literature search yielded six studies with 14 effect sizes of interest; pooled effect size was small to medium (d = -0.35). Combined with a narrative synthesis of six studies without a comparison group, these results show that EF get impaired after COVID-19; although, in most cases the impairment is transient and does not seem to be severe. These results specify the picture of 'brain fog' and may help to discover its mechanisms and ways of helping people with long COVID.}, } @article {pmid36813431, year = {2023}, author = {Friedel, DM and Cappell, MS}, title = {Diarrhea and Coronavirus Disease 2019 Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {59-75}, pmid = {36813431}, issn = {1558-1942}, mesh = {Humans ; *COVID-19/complications ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Diarrhea ; *Gastrointestinal Diseases/diagnosis ; }, abstract = {The global coronavirus disease-2019 (COVID-19) pandemic has caused significant morbidity and mortality, thoroughly affected daily living, and caused severe economic disruption throughout the world. Pulmonary symptoms predominate and account for most of the associated morbidity and mortality. However, extrapulmonary manifestations are common in COVID-19 infections, including gastrointestinal (GI) symptoms, such as diarrhea. Diarrhea affects approximately 10% to 20% of COVID-19 patients. Diarrhea can occasionally be the presenting and only COVID-19 symptom. Diarrhea in COVID-19 subjects is usually acute but is occasionally chronic. It is typically mild-to-moderate and nonbloody. It is usually much less clinically important than pulmonary or potential thrombotic disorders. Occasionally the diarrhea can be profuse and life-threatening. The entry receptor for COVID-19, angiotensin converting enzyme-2, is found throughout the GI tract, especially in the stomach and small intestine, which provides a pathophysiologic basis for local GI infection. COVID-19 virus has been documented in feces and in GI mucosa. Treatment of COVID-19 infection, especially antibiotic therapy, is a common culprit of the diarrhea, but secondary infections including bacteria, especially Clostridioides difficile, are sometimes implicated. Workup for diarrhea in hospitalized patients usually includes routine chemistries; basic metabolic panel; and a complete hemogram; sometimes stool studies, possibly including calprotectin or lactoferrin; and occasionally abdominal CT scan or colonoscopy. Treatment for the diarrhea is intravenous fluid infusion and electrolyte supplementation as necessary, and symptomatic antidiarrheal therapy, including Loperamide, kaolin-pectin, or possible alternatives. Superinfection with C difficile should be treated expeditiously. Diarrhea is prominent in post-COVID-19 (long COVID-19), and is occasionally noted after COVID-19 vaccination. The spectrum of diarrhea in COVID-19 patients is presently reviewed including the pathophysiology, clinical presentation, evaluation, and treatment.}, } @article {pmid36813422, year = {2023}, author = {Rizvi, A and Ziv, Y and Crawford, JM and Trindade, AJ}, title = {Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {139-156}, pmid = {36813422}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Disease Progression ; }, abstract = {Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.}, } @article {pmid36813419, year = {2023}, author = {Summa, KC and Hanauer, SB}, title = {COVID-19 and Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {103-113}, pmid = {36813419}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Vaccines ; Pandemics ; *Inflammatory Bowel Diseases ; }, abstract = {The COVID-19 pandemic caused by the SARS-CoV-2 virus represents an unprecedented global health crisis. Safe and effective vaccines were rapidly developed and deployed that reduced COVID-19-related severe disease, hospitalization, and death. Patients with inflammatory bowel disease are not at increased risk of severe disease or death from COVID-19, and data from large cohorts of patients with inflammatory bowel disease demonstrate that COVID-19 vaccination is safe and effective. Ongoing research is clarifying the long-term impact of SARS-CoV-2 infection on patients with inflammatory bowel disease, long-term immune responses to COVID-19 vaccination, and optimal timing for repeated COVID-19 vaccination doses.}, } @article {pmid36813418, year = {2023}, author = {Meringer, H and Wang, A and Mehandru, S}, title = {The Pathogenesis of Gastrointestinal, Hepatic, and Pancreatic Injury in Acute and Long Coronavirus Disease 2019 Infection.}, journal = {Gastroenterology clinics of North America}, volume = {52}, number = {1}, pages = {1-11}, pmid = {36813418}, issn = {1558-1942}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Gastrointestinal Tract ; Liver ; Dysbiosis ; *Gastrointestinal Diseases ; }, abstract = {The gastrointestinal (GI) tract is targeted by severe acute respiratory syndrome coronavirus-2. The present review examines GI involvement in patients with long coronavirus disease and discusses the underlying pathophysiological mechanisms that include viral persistence, mucosal and systemic immune dysregulation, microbial dysbiosis, insulin resistance, and metabolic abnormalities. Due to the complex and potentially multifactorial nature of this syndrome, rigorous clinical definitions and pathophysiology-based therapeutic approaches are warranted.}, } @article {pmid36813250, year = {2023}, author = {Qasmieh, SA and Robertson, MM and Teasdale, CA and Kulkarni, SG and Jones, HE and McNairy, M and Borrell, LN and Nash, D}, title = {The prevalence of SARS-CoV-2 infection and long COVID in U.S. adults during the BA.4/BA.5 surge, June-July 2022.}, journal = {Preventive medicine}, volume = {169}, number = {}, pages = {107461}, pmid = {36813250}, issn = {1096-0260}, mesh = {Adult ; Humans ; Adolescent ; Young Adult ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; Cross-Sectional Studies ; Prevalence ; SARS-CoV-2 ; }, abstract = {Due to changes in SARS-CoV-2 testing practices, passive case-based surveillance may be an increasingly unreliable indicator for monitoring the burden of SARS-CoV-2, especially during surges. We conducted a cross-sectional survey of a population-representative sample of 3042 U.S. adults between June 30 and July 2, 2022, during the Omicron BA.4/BA.5 surge. Respondents were asked about SARS-CoV-2 testing and outcomes, COVID-like symptoms, contact with cases, and experience with prolonged COVID-19 symptoms following prior infection. We estimated the weighted age and sex-standardized SARS-CoV-2 prevalence, during the 14-day period preceding the interview. We estimated age and gender adjusted prevalence ratios (aPR) for current SARS-CoV-2 infection using a log-binomial regression model. An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period-equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4,2.2) and Hispanic adults (aPR 2.4, 95% CI 2.0, 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection >4 weeks prior reported long COVID symptoms. The inequitable distribution of SARS-CoV-2 prevalence during the BA.4/BA.5 surge will likely drive inequities in the future burden of long COVID.}, } @article {pmid36811824, year = {2023}, author = {Bridger Staatz, C and Bann, D and Ploubidis, GB and Goodman, A and Silverwood, RJ}, title = {Age of First Overweight and Obesity, COVID-19 and Long COVID in Two British Birth Cohorts.}, journal = {Journal of epidemiology and global health}, volume = {13}, number = {1}, pages = {140-153}, pmid = {36811824}, issn = {2210-6014}, support = {MR/V002147/1/MRC_/Medical Research Council/United Kingdom ; MR/P023444/1/MRC_/Medical Research Council/United Kingdom ; COV-LT-0009-28654/DH_/Department of Health/United Kingdom ; }, mesh = {Child ; Humans ; Middle Aged ; *Overweight ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Birth Cohort ; Cross-Sectional Studies ; *COVID-19 ; Obesity ; Body Mass Index ; }, abstract = {Longer exposure to obesity, and thus a longer period in an inflamed state, may increase susceptibility to infectious diseases and worsen severity. Previous cross-sectional work finds higher BMI is related to worse COVID-19 outcomes, but less is known about associations with BMI across adulthood. To examine this, we used body mass index (BMI) collected through adulthood in the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participants were grouped by the age they were first overweight (> 25 kg/m[2]) and obese (> 30 kg/m[2]). Logistic regression was used to assess associations with COVID-19 (self-reported and serology-confirmed), severity (hospital admission and contact with health services) and long-COVID reported at ages 62 (NCDS) and 50 (BCS70). An earlier age of obesity and overweight, compared to those who never became obese or overweight, was associated with increased odds of adverse COVID-19 outcomes, but results were mixed and often underpowered. Those with early exposure to obesity were over twice as likely in NCDS (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.17-4.00) and three times as likely in BCS70 (OR 3.01, 95% CI 1.74-5.22) to have long COVID. In NCDS they were also over four times as likely to be admitted to hospital (OR 4.69, 95% CI 1.64-13.39). Most associations were somewhat explained by contemporaneous BMI or reported health, diabetes or hypertension; however, the association with hospital admission in NCDS remained. An earlier age of obesity onset is related to COVID-19 outcomes in later life, providing evidence of the long-term impact of raised BMI on infectious disease outcomes in midlife.}, } @article {pmid36810758, year = {2023}, author = {Mazurkiewicz, I and Chatys-Bogacka, Ż and Słowik, J and Zdanecka, M and Siwiec-Koźlik, A and Słowik, A and Drabik, L and Wnuk, M}, title = {Course of fatigue among patients previously hospitalised due to COVID-19.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {1}, pages = {101-110}, doi = {10.5603/PJNNS.a2023.0015}, pmid = {36810758}, issn = {0028-3843}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/epidemiology ; Retrospective Studies ; Hospitalization ; }, abstract = {INTRODUCTION: Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection.

MATERIAL AND METHODS: Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection.

RESULTS: We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [β 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, β -0.12 (-0.28; -0.01), p = 0.029].

CONCLUSIONS: Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and - only for the acute phase - age.}, } @article {pmid36810225, year = {2023}, author = {}, title = {Correction to "Treating common and potentially modifiable symptoms of post-COVID-19 condition (long COVID) in adults".}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {7}, pages = {E276}, pmid = {36810225}, issn = {1488-2329}, } @article {pmid36810170, year = {2023}, author = {Adler, L and Israel, M and Yehoshua, I and Azuri, J and Hoffman, R and Shahar, A and Mizrahi Reuveni, M and Grossman, Z}, title = {Long COVID symptoms in Israeli children with and without a history of SARS-CoV-2 infection: a cross-sectional study.}, journal = {BMJ open}, volume = {13}, number = {2}, pages = {e064155}, pmid = {36810170}, issn = {2044-6055}, mesh = {Adolescent ; Child ; Humans ; Aged ; Child, Preschool ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Cross-Sectional Studies ; Israel ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: To estimate the prevalence of long COVID symptoms in children with and without a history of SARS-CoV-2 infection and to evaluate factors associated with long COVID.

DESIGN: A nationwide cross-sectional study.

SETTING: Primary care.

PARTICIPANTS: 3240 parents of children aged 5-18 with and without SARS-CoV-2 infection completed an online questionnaire (11.9% response rate); 1148 and 2092 with/without a history of infection, respectively.

Primary outcome was the prevalence of long COVID symptoms in children with/without a history of infection. Secondary outcomes were the factors associated with the presence of long COVID symptoms and with failure to return to baseline health status in children with a history of infection including gender, age, time from illness, symptomatic illness and vaccine status.

RESULTS: Most long COVID symptoms were more prevalent in children with a history of SARS-CoV-2 infection: headaches (211 (18.4%) vs 114 (5.4%), p<0.001), weakness (173 (15.1%) vs 70 (3.3%), p<0.001), fatigue (141 (12.3%) vs 133 (6.4%), p<0.001) and abdominal pain (109 (9.5%) vs 79 (3.8%), p<0.001). Most long COVID symptoms in children with a history of SARS-CoV-2 infection were more prevalent in the older age group (12-18) compared with the younger age group (5-11). Some symptoms were more prevalent in children without a history of SARS-CoV-2 infection, including attention problems with school malfunctioning (225 (10.8%) vs 98 (8.5%), p=0.05), stress (190 (9.1%) vs 65 (5.7%), p<0.001), social problems (164 (7.8%) vs 32 (2.8%)) and weight changes (143 (6.8%) vs 43 (3.7%), p<0.001).

CONCLUSION: This study suggests that the prevalence of long COVID symptoms in children with a history of SARS-CoV-2 infection might be higher and more prevalent in adolescents than in young children. Some of the symptoms, mainly somatic symptoms, were more prevalent in children without a history of SARS-CoV-2 infection, highlighting the impact of the pandemic itself rather than the infection.}, } @article {pmid36809921, year = {2023}, author = {Patel, MA and Knauer, MJ and Nicholson, M and Daley, M and Van Nynatten, LR and Cepinskas, G and Fraser, DD}, title = {Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {29}, number = {1}, pages = {26}, pmid = {36809921}, issn = {1528-3658}, mesh = {Humans ; *COVID-19 ; Proteomics ; Case-Control Studies ; Machine Learning ; Post-Acute COVID-19 Syndrome ; Biomarkers ; }, abstract = {BACKGROUND: Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as "Long-COVID". A lack of Long-COVID biomarkers and pathophysiological mechanisms limits effective diagnosis, treatment and disease surveillance. We performed targeted proteomics and machine learning analyses to identify novel blood biomarkers of Long-COVID.

METHODS: A case-control study comparing the expression of 2925 unique blood proteins in Long-COVID outpatients versus COVID-19 inpatients and healthy control subjects. Targeted proteomics was accomplished with proximity extension assays, and machine learning was used to identify the most important proteins for identifying Long-COVID patients. Organ system and cell type expression patterns were identified with Natural Language Processing (NLP) of the UniProt Knowledgebase.

RESULTS: Machine learning analysis identified 119 relevant proteins for differentiating Long-COVID outpatients (Bonferonni corrected P < 0.01). Protein combinations were narrowed down to two optimal models, with nine and five proteins each, and with both having excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, F1 = 1.00). NLP expression analysis highlighted the diffuse organ system involvement in Long-COVID, as well as the involved cell types, including leukocytes and platelets, as key components associated with Long-COVID.

CONCLUSIONS: Proteomic analysis of plasma from Long-COVID patients identified 119 highly relevant proteins and two optimal models with nine and five proteins, respectively. The identified proteins reflected widespread organ and cell type expression. Optimal protein models, as well as individual proteins, hold the potential for accurate diagnosis of Long-COVID and targeted therapeutics.}, } @article {pmid36809148, year = {2023}, author = {Brandt, CT and Wiese, L and Christiansen, KM and Agergaard, J}, title = {Antibodies to Nucleocapsid Are Not Diagnostic for Long COVID.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0490022}, pmid = {36809148}, issn = {2165-0497}, } @article {pmid36807444, year = {2023}, author = {Islam, MS and Wang, Z and Abdel-Mohsen, M and Chen, X and Montaner, LJ}, title = {Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID.}, journal = {Journal of leukocyte biology}, volume = {113}, number = {3}, pages = {236-254}, doi = {10.1093/jleuko/qiac001}, pmid = {36807444}, issn = {1938-3673}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19 ; Leukocytes ; Antigens, Viral ; Autoantibodies ; Disease Progression ; }, abstract = {A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This phenomenon, termed post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of autoantibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder, including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include the degree of host responses (inflammation, NETinjury), residual viral antigen (persistent antigen), and exogenous factors (microbial translocation). Determinants of PASC may be amplified by comorbidities, age, and sex.}, } @article {pmid36806080, year = {2023}, author = {van der Zalm, MM and Dona', D and Rabie, H}, title = {Pediatric coronavirus disease 2019 in Africa.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {2}, pages = {176-183}, pmid = {36806080}, issn = {1531-698X}, support = {K43 TW011028/TW/FIC NIH HHS/United States ; }, mesh = {SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Africa/epidemiology ; *COVID-19/epidemiology/complications ; Humans ; Post-Acute COVID-19 Syndrome ; Infant ; Child ; }, abstract = {PURPOSE OF REVIEW: Three years into the coronavirus disease 2019 (COVID-19) pandemic, data on pediatric COVID-19 from African settings is limited. Understanding the impact of the pandemic in this setting with a high burden of communicable and noncommunicable diseases is critical to implementing effective interventions in public health programs.

RECENT FINDINGS: More severe COVID-19 has been reported in African settings, with especially infants and children with underlying comorbidities at highest risk for more severe disease. Data on the role of tuberculosis and HIV remain sparse. Compared to better resourced settings more children with multisystem inflammatory disease (MISC) are younger than 5 years and there is higher morbidity in all settings and increased mortality in some settings. Several reports suggest decreasing prevalence and severity of MIS-C disease with subsequent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant waves. Whether this decrease continues remains to be determined. Thus far, data on long-COVID in African settings is lacking and urgently needed considering the severity of the disease seen in the African population.

SUMMARY: Considering the differences seen in the severity of disease and short-term outcomes, there is an urgent need to establish long-term outcomes in children with COVID-19 and MIS-C in African children, including lung health assessment.}, } @article {pmid36806075, year = {2023}, author = {Chen, X and Bakal, J and Whitten, T and Waldie, B and Ho, C and Wright, P and Hassam, S and Norris, C}, title = {Assessing the impact of COVID-19 pandemic on the health of residents and the healthcare system in Alberta, Canada: an observational study-The Alberta POST-COVID Follow-up Study.}, journal = {BMJ open}, volume = {13}, number = {2}, pages = {e067449}, pmid = {36806075}, issn = {2044-6055}, mesh = {Humans ; Alberta/epidemiology ; Follow-Up Studies ; *Pandemics ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Patient Acceptance of Health Care ; }, abstract = {INTRODUCTION: Very little is known about how the COVID-19 pandemic has affected the health of residents and the healthcare system in Alberta, Canada. The purpose of this study is to establish an observational study to characterise the health of residents in Alberta, Canada, over time, covering a population that tested negative or positive for COVID-19 during the pandemic. The primary outcome is to characterise 'long COVID-19' and the health status of residents during the COVID-19 pandemic. Secondary outcomes include the estimation of the risk of and risk factors associated with adverse health outcomes and healthcare utilisation and burdens.

METHODS AND ANALYSIS: This is a population-level provincial observational study which will follow-up with Alberta residents who underwent testing for COVID-19 and completed surveys adapted from the ISARIC COVID-19 long-term follow-up survey. The survey data will be linked with medical records. Statistical analyses will be carried out to characterise 'long COVID-19' and the health status of residents during the pandemic. The outcomes of this study will inform strategies for primary care and rehabilitation services to prevent chronic consequences; contribute to healthcare management, interventional studies, rehabilitation and health management to reduce overall morbidity and improve long-term outcomes of COVID-19 and the COVID-19 pandemic and potentially guide a self-evaluation of a remote monitoring system to manage individuals' health.

ETHICS AND DISSEMINATION: This study was reviewed and approved by the University of Alberta ethics committee (Study ID: Pro00112053 & Pro00113039) on 13 August 2021 and adheres to the Alberta Health Services research information management policy. Study results will be used to manage clinical care, published in peer-reviewed journals and presented at local, national and international conferences.

PROTOCOL VERSION: 6 June 2022 EUROQOL ID: 161 015.}, } @article {pmid36806073, year = {2023}, author = {Herrett, E and Tomlin, K and Lin, LY and Tomlinson, LA and Jit, M and Briggs, A and Marks, M and Sandmann, F and Parry, J and Bates, C and Morley, J and Bacon, S and Butler-Cole, B and Mahalingasivam, V and Dennison, A and Smith, D and Gabriel, E and Mehrkar, A and Goldacre, B and Smeeth, L and Eggo, RMM}, title = {Protocol for an OpenSAFELY cohort study collecting patient-reported outcome measures using the TPP Airmid smartphone application and linked big data to quantify the health and economic costs of long COVID (OpenPROMPT).}, journal = {BMJ open}, volume = {13}, number = {2}, pages = {e071261}, pmid = {36806073}, issn = {2044-6055}, support = {MR/W016729/1/MRC_/Medical Research Council/United Kingdom ; 222097/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; MR/V015757/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MR/V015737/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC-20059/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Big Data ; Cohort Studies ; *COVID-19/prevention & control ; COVID-19 Testing ; *Mobile Applications ; Patient Reported Outcome Measures ; Post-Acute COVID-19 Syndrome ; Smartphone ; State Medicine ; }, abstract = {INTRODUCTION: The impact of long COVID on health-related quality of-life (HRQoL) and productivity is not currently known. It is important to understand who is worst affected by long COVID and the cost to the National Health Service (NHS) and society, so that strategies like booster vaccines can be prioritised to the right people. OpenPROMPT aims to understand the impact of long COVID on HRQoL in adults attending English primary care.

METHODS AND ANALYSIS: We will ask people to participate in this cohort study through a smartphone app (Airmid), and completing a series of questionnaires held within the app. Questionnaires will ask about HRQoL, productivity and symptoms of long COVID. Participants will be asked to fill in the questionnaires once a month, for 90 days. Questionnaire responses will be linked, where possible, to participants' existing health records from primary care, secondary care, and COVID testing and vaccination data. Analysis will take place using the OpenSAFELY data platform and will estimate the impact of long COVID on HRQoL, productivity and cost to the NHS.

ETHICS AND DISSEMINATION: The Proportionate Review Sub-Committee of the South Central-Berkshire B Research Ethics Committee has reviewed and approved the study and have agreed that we can ask people to take part (22/SC/0198). Our results will provide information to support long-term care, and make recommendations for prevention of long COVID in the future.

TRIAL REGISTRATION NUMBER: NCT05552612.}, } @article {pmid36805019, year = {2023}, author = {Fernández-Ortega, MÁ and Ponce-Rosas, ER and Muñiz-Salinas, DA and Rodríguez-Mendoza, O and Nájera Chávez, P and Sánchez-Pozos, V and Dávila-Mendoza, R and Barrell, AE}, title = {Cognitive dysfunction, diabetes mellitus 2 and arterial hypertension: Sequelae up to one year of COVID-19.}, journal = {Travel medicine and infectious disease}, volume = {52}, number = {}, pages = {102553}, pmid = {36805019}, issn = {1873-0442}, mesh = {Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; *Diabetes Mellitus, Type 2/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Hospitalization ; *Hypertension/epidemiology ; *Cognitive Dysfunction/epidemiology/etiology ; }, abstract = {BACKGROUND: Covid symptoms reflect its multisystem nature, in addition to its positive relationship between the severity of the condition and the severity of the long COVID.

OBJECTIVE: To identify the factors associated with the prevalence of SEQUELAE DUE TO COVID-19 one year after their hospital discharge due to severe pneumonia.

METHOD: Longitudinal, analytical, prospective and comparative study. 71 covid-19 pneumonia survivors were followed. Two telephone interviews were conducted to each patient; the first at 5 months of discharge and the second at 12 months from the mentioned date. We included questions of 40 symptoms, in addition to the questioning of diabetes mellitus and/or systemic hypertension with a mentioned onset during the hospitalization or after hospital discharge due to COVID-19.

RESULTS: Of the 37 patients without complications and without comorbidities prior to hospitalization, 11 (29.7%) developed arterial hypertension during or after discharge and 17 (45.9%) developed diabetes mellitus before five months. Short-term memory loss was an upward sequel in the two measurements, 24.3% and 41.9% respectively.

CONCLUSIONS: Type 2 diabetes mellitus and high blood pressure detected at five months was temporary and reversed in many cases at twelve months. It will be important to deepen the study of brain damage and cognitive dysfunction, characterized by memory loss.}, } @article {pmid36804609, year = {2023}, author = {Agergaard, J and Yamin Ali Khan, B and Engell-Sørensen, T and Schiøttz-Christensen, B and Østergaard, L and Hejbøl, EK and Schrøder, HD and Andersen, H and Blicher, JU and Holm Pedersen, T and Harbo, T and Tankisi, H and , }, title = {Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {148}, number = {}, pages = {65-75}, doi = {10.1016/j.clinph.2023.01.010}, pmid = {36804609}, issn = {1872-8952}, mesh = {Humans ; Electromyography/methods ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/complications ; *Muscular Diseases ; Muscle, Skeletal ; Fatigue ; }, abstract = {OBJECTIVE: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.

METHODS: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.

RESULTS: Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.

CONCLUSIONS: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.

SIGNIFICANCE: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.}, } @article {pmid36803675, year = {2023}, author = {Chen, H and Zhang, L and Zhang, Y and Chen, G and Wang, D and Chen, X and Wang, Z and Wang, J and Che, X and Horita, N and Seki, N}, title = {Prevalence and clinical features of long COVID from omicron infection in children and adults.}, journal = {The Journal of infection}, volume = {86}, number = {4}, pages = {e97-e99}, doi = {10.1016/j.jinf.2023.02.015}, pmid = {36803675}, issn = {1532-2742}, mesh = {Adult ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; Prevalence ; *COVID-19 ; }, } @article {pmid36802122, year = {2023}, author = {Hugon, J}, title = {Long COVID: Does SARS-CoV-2 induce lingering brain lesions?.}, journal = {European journal of neurology}, volume = {30}, number = {5}, pages = {1165-1166}, doi = {10.1111/ene.15751}, pmid = {36802122}, issn = {1468-1331}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases ; Brain/diagnostic imaging ; }, abstract = {Hundreds of millions of COVID cases have been reported so far and long-term lingering clinical symptoms are frequent and are called long COVID. Neurological signs including cognitive complaints are often described in long Covid. In COVID patients, the Sars-Cov-2 virus can reach the brain and could be responsible for cerebral anomalies observed in long COVID. Long-term careful clinical follow-up of these patients is necessary to detect early signs of neurodegeneration.}, } @article {pmid36802108, year = {2024}, author = {Jain, V and Nabi, N and Aggarwal, S and Alam, Z and Chandra, K and Singh, D and Kashyap, V and Islam, F and Kohli, S}, title = {Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {115-125}, doi = {10.1111/jocn.16652}, pmid = {36802108}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/epidemiology ; Quality of Life ; Tertiary Care Centers ; Alopecia ; Dyspnea ; Fatigue/epidemiology ; Mental Fatigue ; Memory Disorders ; }, abstract = {OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors.

BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection.

DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements.

METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters.

RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05).

CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS.

The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.}, } @article {pmid36801258, year = {2023}, author = {Simonin, Y}, title = {Neurobiology of long-COVID: Hypotheses and unanswered questions.}, journal = {Anaesthesia, critical care & pain medicine}, volume = {42}, number = {3}, pages = {101201}, pmid = {36801258}, issn = {2352-5568}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Neurobiology ; }, } @article {pmid36801082, year = {2023}, author = {Park, N and Oberlin, L and Cherestal, S and Bueno Castellano, C and Dargis, M and Wyka, KE and Jaywant, A and Kanellopoulos, D}, title = {Trajectory and outcomes of psychiatric symptoms in first-wave COVID-19 survivors referred for telepsychotherapy.}, journal = {General hospital psychiatry}, volume = {81}, number = {}, pages = {86-88}, pmid = {36801082}, issn = {1873-7714}, support = {UL1 TR002384/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Psychotherapy ; *COVID-19 ; *Telemedicine ; *Mental Disorders/epidemiology/therapy ; }, } @article {pmid36799525, year = {2023}, author = {Chatys-Bogacka, Ż and Mazurkiewicz, I and Słowik, J and Nowak, K and Sydor, W and Wizner, B and Słowik, A and Wnuk, M and Drabik, L}, title = {Sex-related patient-reported brain fog symptoms in non-hospitalised COVID-19 patients.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {1}, pages = {111-120}, doi = {10.5603/PJNNS.a2023.0010}, pmid = {36799525}, issn = {0028-3843}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; Cross-Sectional Studies ; Reproducibility of Results ; Patient Reported Outcome Measures ; Brain ; }, abstract = {INTRODUCTION: Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex.

MATERIAL AND METHODS: We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0-4, 4-12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab.

RESULTS: The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161-248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38-6.72; 4-12 weeks, OR 2.51, 95% CI: 1.02-6.14; > 12 weeks, OR 3.74, 95% CI: 1.12-12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41-4.54; 4-12 weeks, OR 3.74, 95% CI: 1.93-7.24; > 12 weeks, OR 2.00, 95% CI: 1.01-3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36-5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44-4.48 and OR 2.43, 95% CI: 1.37-4.31 for < 4 and 4-12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted.

CONCLUSIONS: Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog.}, } @article {pmid36799524, year = {2023}, author = {Czarnowska, A and Zajkowska, J and Kułakowska, A}, title = {Impact of SARS-CoV-2 on the nervous system.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {1}, pages = {26-35}, doi = {10.5603/PJNNS.a2023.0009}, pmid = {36799524}, issn = {0028-3843}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19/epidemiology ; Pandemics ; *Nervous System Diseases/epidemiology/etiology ; }, abstract = {INTRODUCTION: The ongoing COVID-19 pandemic is the largest global public health struggle. The spread of the novel coronavirus had resulted in almost 7 million deaths worldwide by January 2023.

STATE OF THE ART: The most common symptoms during the acute phase of COVID-19 are respiratory. However, many individuals present various neurological deficits at different stages of the infection. Furthermore, there are post-infectious complications that can be present within weeks after the initial symptoms. Both the central and peripheral nervous systems (CNS and PNS, respectively) can be affected. Many potential mechanisms and hypotheses regarding the neuropathology behind COVID-19 have been proposed.

CLINICAL IMPLICATIONS: The distribution of neurological symptoms during COVID-19 infection among studies differs greatly, which is mostly due to differing inclusion criteria. One of the most significant is incidence involving CNS circulation. In this review, we present basic information regarding the novel coronavirus, the possible routes along which the pathogen can reach the nervous system, neuropathology mechanisms, and neurological symptoms following COVID-19.

FUTURE DIRECTIONS: It seems that many factors, resulting both from the properties of the virus and from systemic responses to infection, play a role in developing neurological symptoms. The long-term effect of the virus on the nervous system is still unknown.}, } @article {pmid36798288, year = {2023}, author = {Bodansky, A and Wang, CY and Saxena, A and Mitchell, A and Takahashi, S and Anglin, K and Huang, B and Hoh, R and Lu, S and Goldberg, SA and Romero, J and Tran, B and Kirtikar, R and Grebe, H and So, M and Greenhouse, B and Durstenfeld, MS and Hsue, PY and Hellmuth, J and Kelly, JD and Martin, JN and Anderson, MS and Deeks, SG and Henrich, TJ and DeRisi, JL and Peluso, MJ}, title = {Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36798288}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; K12 HD000850/HD/NICHD NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; }, abstract = {Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.}, } @article {pmid36798286, year = {2023}, author = {Yin, K and Peluso, MJ and Luo, X and Thomas, R and Shin, MG and Neidleman, J and Andrew, A and Young, K and Ma, T and Hoh, R and Anglin, K and Huang, B and Argueta, U and Lopez, M and Valdivieso, D and Asare, K and Deveau, TM and Munter, SE and Ibrahim, R and Ständker, L and Lu, S and Goldberg, SA and Lee, SA and Lynch, KL and Kelly, JD and Martin, JN and Münch, J and Deeks, SG and Henrich, TJ and Roan, NR}, title = {Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36798286}, issn = {2692-8205}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; S10 RR028962/RR/NCRR NIH HHS/United States ; S10 OD018040/OD/NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, abstract = {Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple "omics" assays (CyTOF, RNAseq/scRNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. RNAseq/scRNAseq and Olink analyses similarly revealed immune dysregulatory mechanisms, along with non-immune associated perturbations, in individuals with LC. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.}, } @article {pmid36795973, year = {2023}, author = {Karbalaeimahdi, M and Farajnia, S and Bargahi, N and Ghadiri-Moghaddam, F and Rasouli Jazi, HR and Bakhtiari, N and Ghasemali, S and Zarghami, N}, title = {The Role of Interferons in Long Covid Infection.}, journal = {Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, volume = {43}, number = {2}, pages = {65-76}, doi = {10.1089/jir.2022.0193}, pmid = {36795973}, issn = {1557-7465}, mesh = {Humans ; Interferons/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Neurodegenerative Diseases ; Lung ; }, abstract = {Although the new generation of vaccines and anti-COVID-19 treatment regimens facilitated the management of acute COVID-19 infections, concerns about post-COVID-19 syndrome or Long Covid are rising. This issue can increase the incidence and morbidity of diseases such as diabetes, and cardiovascular, and lung infections, especially among patients suffering from neurodegenerative disease, cardiac arrhythmias, and ischemia. There are numerous risk factors that cause COVID-19 patients to experience post-COVID-19 syndrome. Three potential causes attributed to this disorder include immune dysregulation, viral persistence, and autoimmunity. Interferons (IFNs) are crucial in all aspects of post-COVID-19 syndrome etiology. In this review, we discuss the critical and double-edged role of IFNs in post-COVID-19 syndrome and how innovative biomedical approaches that target IFNs can reduce the occurrence of Long Covid infection.}, } @article {pmid36795701, year = {2023}, author = {Hossain, MM and Das, J and Rahman, F and Nesa, F and Hossain, P and Islam, AMK and Tasnim, S and Faizah, F and Mazumder, H and Purohit, N and Ramirez, G}, title = {Living with "long COVID": A systematic review and meta-synthesis of qualitative evidence.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0281884}, pmid = {36795701}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Qualitative Research ; Health Personnel/psychology ; Social Support ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Long-term health consequences of coronavirus disease (COVID-19), also known as "long COVID," has become a global health concern. In this systematic review, we aimed to synthesize the qualitative evidence on lived experiences of people living with long COVID that may inform health policymaking and practice.

METHODS: We searched six major databases and additional sources and systematically retrieved relevant qualitative studies and conducted a meta-synthesis of key findings using the Joanna Briggs Institute (JBI) guidelines and reporting standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist.

RESULTS: We found 15 articles representing 12 studies out of 619 citations from different sources. These studies provided 133 findings that were categorized into 55 categories. All categories were aggregated to the following synthesized findings: living with complex physical health problems, psychosocial crises of long COVID, slow recovery and rehabilitation, digital resources and information management, changes in social support, and experiences with healthcare providers, services, and systems. Ten studies were from the UK, and others were from Denmark and Italy, which highlights a critical lack of evidence from other countries.

CONCLUSIONS: More representative research is needed to understand long COVID-related experiences from diverse communities and populations. The available evidence informs a high burden of biopsychosocial challenges among people with long COVID that would require multilevel interventions such as strengthening health and social policies and services, engaging patients and caregivers in making decisions and developing resources, and addressing health and socioeconomic disparities associated with long COVID through evidence-based practice.}, } @article {pmid36795575, year = {2023}, author = {Ahn, B and Choi, SH and Yun, KW}, title = {Non-neuropsychiatric Long COVID Symptoms in Children Visiting a Pediatric Infectious Disease Clinic After an Omicron Surge.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {5}, pages = {e143-e145}, pmid = {36795575}, issn = {1532-0987}, mesh = {Adolescent ; Humans ; Child ; *COVID-19/epidemiology ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Ambulatory Care Facilities ; *Communicable Diseases ; }, abstract = {Although much interest has emerged regarding post-COVID conditions, data on children and adolescents are limited. The prevalence of long COVID and common symptoms were analyzed in this case-control study of 274 children. Prolonged non-neuropsychiatric symptoms were more frequent in the case group (17.0% and 4.8%, P = 0.004). Abdominal pain (6.6%) was the most common long COVID symptom.}, } @article {pmid36794902, year = {2023}, author = {O'Brien, S and Buckley, C and Butler, T and Cunningham, Z and Keane, S and McArdle, E and Mitchell, P and Donnelly, SC}, title = {Persistent diaphragmatic weakness and peripheral muscle weakness are associated with anosmia in the long-COVID syndrome.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {116}, number = {7}, pages = {603-604}, doi = {10.1093/qjmed/hcad025}, pmid = {36794902}, issn = {1460-2393}, mesh = {Humans ; *Anosmia ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Muscle Weakness/etiology ; }, } @article {pmid36793333, year = {2023}, author = {Jamaica Balderas, LMDC and Navarro Fernández, A and Dragustinovis Garza, SA and Orellana Jerves, MI and Solís Figueroa, WE and Koretzky, SG and Márquez González, H and Klünder Klünder, M and Espinosa, JG and Nieto Zermeño, J and Villa Guillén, M and Rosales Uribe, RE and Olivar López, V}, title = {Long COVID in children and adolescents: COVID-19 follow-up results in third-level pediatric hospital.}, journal = {Frontiers in pediatrics}, volume = {11}, number = {}, pages = {1016394}, pmid = {36793333}, issn = {2296-2360}, abstract = {INTRODUCTION: In children, the manifestations of coronavirus disease 2019 (COVID-19) in the acute phase are considered mild compared with those in adults; however, some children experience a severe disease that requires hospitalization. This study was designed to present the operation and follow-up results of the Post-COVID-19 Detection and Monitoring Sequels Clinic of Hospital Infantil de Mexico Federico Gómez in managing children with a history of SARS-CoV-2 infection.

METHODS: This was a prospective study conducted from July 2020 to December 2021, which included 215 children aged 0-18 years who tested positive for SARS-CoV-2 on polymerase chain reaction and/or immunoglobulin G test. The follow-up was conducted in the pulmonology medical consultation; ambulatory and hospitalized patients were assessed at 2, 4, 6, and 12 months.

RESULTS: The median age of the patients was 9.02 years, and neurological, endocrinological, pulmonary, oncological, and cardiological comorbidities were the most commonly observed among the patients. Moreover, 32.6% of the children had persistent symptoms at 2 months, 9.3% at 4 months, and 2.3% at 6 months, including dyspnea, dry cough, fatigue, and runny nose; the main acute complications were severe pneumonia, coagulopathy, nosocomial infections, acute renal injury, cardiac dysfunction, and pulmonary fibrosis. The more representative sequelae were alopecia, radiculopathy, perniosis, psoriasis, anxiety, and depression.

CONCLUSIONS: This study showed that children experience persistent symptoms, such as dyspnea, dry cough, fatigue, and runny nose, although to a lesser extent than adults, with significant clinical improvement 6 months after the acute infection. These results indicate the importance of monitoring children with COVID-19 through face-to-face consultations or telemedicine, with the objective of offering multidisciplinary and individualized care to preserve the health and quality of life of these children.}, } @article {pmid36793086, year = {2023}, author = {Pfaff, ER and Madlock-Brown, C and Baratta, JM and Bhatia, A and Davis, H and Girvin, A and Hill, E and Kelly, E and Kostka, K and Loomba, J and McMurry, JA and Wong, R and Bennett, TD and Moffitt, R and Chute, CG and Haendel, M and , and , }, title = {Coding long COVID: characterizing a new disease through an ICD-10 lens.}, journal = {BMC medicine}, volume = {21}, number = {1}, pages = {58}, pmid = {36793086}, issn = {1741-7015}, support = {UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Female ; *Post-Acute COVID-19 Syndrome ; International Classification of Diseases ; Pandemics ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Naming a newly discovered disease is a difficult process; in the context of the COVID-19 pandemic and the existence of post-acute sequelae of SARS-CoV-2 infection (PASC), which includes long COVID, it has proven especially challenging. Disease definitions and assignment of a diagnosis code are often asynchronous and iterative. The clinical definition and our understanding of the underlying mechanisms of long COVID are still in flux, and the deployment of an ICD-10-CM code for long COVID in the USA took nearly 2 years after patients had begun to describe their condition. Here, we leverage the largest publicly available HIPAA-limited dataset about patients with COVID-19 in the US to examine the heterogeneity of adoption and use of U09.9, the ICD-10-CM code for "Post COVID-19 condition, unspecified."

METHODS: We undertook a number of analyses to characterize the N3C population with a U09.9 diagnosis code (n = 33,782), including assessing person-level demographics and a number of area-level social determinants of health; diagnoses commonly co-occurring with U09.9, clustered using the Louvain algorithm; and quantifying medications and procedures recorded within 60 days of U09.9 diagnosis. We stratified all analyses by age group in order to discern differing patterns of care across the lifespan.

RESULTS: We established the diagnoses most commonly co-occurring with U09.9 and algorithmically clustered them into four major categories: cardiopulmonary, neurological, gastrointestinal, and comorbid conditions. Importantly, we discovered that the population of patients diagnosed with U09.9 is demographically skewed toward female, White, non-Hispanic individuals, as well as individuals living in areas with low poverty and low unemployment. Our results also include a characterization of common procedures and medications associated with U09.9-coded patients.

CONCLUSIONS: This work offers insight into potential subtypes and current practice patterns around long COVID and speaks to the existence of disparities in the diagnosis of patients with long COVID. This latter finding in particular requires further research and urgent remediation.}, } @article {pmid36792456, year = {2023}, author = {Jacobs, MM and Evans, E and Ellis, C}, title = {Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19.}, journal = {Journal of the National Medical Association}, volume = {115}, number = {2}, pages = {233-243}, pmid = {36792456}, issn = {1943-4693}, mesh = {Adult ; Female ; Humans ; Male ; Black or African American/psychology/statistics & numerical data ; Cognition ; COVID-19/complications/epidemiology/ethnology/prevention & control ; COVID-19 Vaccines/therapeutic use ; Incidence ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/ethnology/psychology ; United States/epidemiology ; White/psychology/statistics & numerical data ; *Cognitive Dysfunction/diagnosis/epidemiology/ethnology/psychology ; Race Factors ; Sex Factors ; Asian/psychology/statistics & numerical data ; Hispanic or Latino/psychology/statistics & numerical data ; }, abstract = {BACKGROUND: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

METHOD: Data from four releases of the Census Bureau's Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

RESULTS: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

CONCLUSIONS: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.}, } @article {pmid36791431, year = {2023}, author = {Slawson, DC}, title = {Likelihood of Long COVID Varies by Variant, Sex, and Vaccination Status.}, journal = {American family physician}, volume = {107}, number = {2}, pages = {199}, pmid = {36791431}, issn = {1532-0650}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; Vaccination ; }, } @article {pmid36791116, year = {2023}, author = {Forshaw, D and Wall, EC and Prescott, G and Dehbi, HM and Green, A and Attree, E and Hismeh, L and Strain, WD and Crooks, MG and Watkins, C and Robson, C and Banerjee, R and Lorgelly, P and Heightman, M and Banerjee, A and , }, title = {STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0272472}, pmid = {36791116}, issn = {1932-6203}, support = {COV-LT2-0043/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Delivery of Health Care, Integrated ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase III as Topic ; }, abstract = {INTRODUCTION: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace.

METHODS AND ANALYSIS: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately.

ETHICS AND DISSEMINATION: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations.

TRIAL REGISTRATION NUMBER: ISRCTN10665760.}, } @article {pmid36790825, year = {2023}, author = {Ostermann, PN and Schaal, H}, title = {Human brain organoids to explore SARS-CoV-2-induced effects on the central nervous system.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2430}, doi = {10.1002/rmv.2430}, pmid = {36790825}, issn = {1099-1654}, mesh = {Humans ; *SARS-CoV-2/physiology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Central Nervous System ; Brain ; Organoids ; }, abstract = {Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). In less than three years, an estimated 600 million infections with SARS-CoV-2 occurred worldwide, resulting in a pandemic with tremendous impact especially on economic and health sectors. Initially considered a respiratory disease, COVID-19, along with its long-term sequelae (long-COVID) rather is a systemic disease. Neurological symptoms like dementia or encephalopathy were reported early during the pandemic as concomitants of the acute phase and as characteristics of long-COVID. An excessive inflammatory immune response is hypothesized to play a major role in this context. However, direct infection of neural cells may also contribute to the neurological aspects of (long)-COVID-19. To mainly explore such direct effects of SARS-CoV-2 on the central nervous system, human brain organoids provide a useful platform. Infecting these three-dimensional tissue cultures allows the study of viral neurotropism as well as of virus-induced effects on single cells or even the complex cellular network within the organoid. In this review, we summarize the experimental studies that used SARS-CoV-2-infected human brain organoids to unravel the complex nature of (long)-COVID-19-related neurological manifestations.}, } @article {pmid36790806, year = {2023}, author = {Perlis, RH and Lunz Trujillo, K and Safarpour, A and Santillana, M and Ognyanova, K and Druckman, J and Lazer, D}, title = {Association of Post-COVID-19 Condition Symptoms and Employment Status.}, journal = {JAMA network open}, volume = {6}, number = {2}, pages = {e2256152}, pmid = {36790806}, issn = {2574-3805}, support = {R01 GM130668/GM/NIGMS NIH HHS/United States ; RF1 MH132335/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Employment ; Surveys and Questionnaires ; Unemployment ; }, abstract = {IMPORTANCE: Little is known about the functional correlates of post-COVID-19 condition (PCC), also known as long COVID, particularly the relevance of neurocognitive symptoms.

OBJECTIVE: To characterize prevalence of unemployment among individuals who did, or did not, develop PCC after acute infection.

This survey study used data from 8 waves of a 50-state US nonprobability internet population-based survey of respondents aged 18 to 69 years conducted between February 2021 and July 2022.

MAIN OUTCOMES AND MEASURES: The primary outcomes were self-reported current employment status and the presence of PCC, defined as report of continued symptoms at least 2 months beyond initial month of symptoms confirmed by a positive COVID-19 test.

RESULTS: The cohort included 15 308 survey respondents with test-confirmed COVID-19 at least 2 months prior, of whom 2236 (14.6%) reported PCC symptoms, including 1027 of 2236 (45.9%) reporting either brain fog or impaired memory. The mean (SD) age was 38.8 (13.5) years; 9679 respondents (63.2%) identified as women and 10 720 (70.0%) were White. Overall, 1418 of 15 308 respondents (9.3%) reported being unemployed, including 276 of 2236 (12.3%) of those with PCC and 1142 of 13 071 (8.7%) of those without PCC; 8229 respondents (53.8%) worked full-time, including 1017 (45.5%) of those with PCC and 7212 (55.2%) without PCC. In survey-weighted regression models excluding retired respondents, the presence of PCC was associated with a lower likelihood of working full-time (odds ratio [OR], 0.71 [95% CI, 0.63-0.80]; adjusted OR, 0.84 [95% CI, 0.74-0.96]) and with a higher likelihood of being unemployed (OR, 1.45 [95% CI, 1.22-1.73]; adjusted OR, 1.23 [95% CI, 1.02-1.48]). The presence of any cognitive symptom was associated with lower likelihood of working full time (OR, 0.70 [95% CI, 0.56-0.88]; adjusted OR, 0.75 [95% CI, 0.59-0.84]).

CONCLUSIONS AND RELEVANCE: PCC was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. The presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to treat and manage PCC symptoms.}, } @article {pmid36790796, year = {2023}, author = {Suran, M}, title = {Long COVID Linked With Unemployment in New Analysis.}, journal = {JAMA}, volume = {329}, number = {9}, pages = {701-702}, doi = {10.1001/jama.2023.0157}, pmid = {36790796}, issn = {1538-3598}, support = {U01 NS114140/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; COVID-19/complications/economics ; Employment/economics ; *Post-Acute COVID-19 Syndrome/complications/economics ; Socioeconomic Factors ; *Unemployment ; }, } @article {pmid36790044, year = {2023}, author = {Glowniak, A and Wojewoda, K and Tarkowski, A}, title = {COVID-19 and long-COVID-19 syndrome related myocarditis: The heart rhythm matters.}, journal = {Cardiology journal}, volume = {30}, number = {1}, pages = {165-166}, pmid = {36790044}, issn = {1898-018X}, mesh = {Humans ; *COVID-19 ; *Myocarditis ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid36789126, year = {2023}, author = {Sasaki, T and Toyama, Y and Horiguchi, T and Hibino, M and Tsuzuki, SI and Hayashi, M and Doi, Y and Iwata, M and Imaizumi, K and Inaba, M}, title = {Post-discharge clinical, laboratory and radiographic features of coronavirus disease 2019 (COVID-19) patients at university hospitals in Japan.}, journal = {Fujita medical journal}, volume = {9}, number = {1}, pages = {30-34}, pmid = {36789126}, issn = {2189-7255}, abstract = {OBJECTIVES: Coronavirus disease 2019 (COVID-19) has affected nearly half million people in Japan. However, information on the prolonged symptoms as well as laboratory and radiographic findings after hospital discharge remains limited.

METHODS: We retrospectively collected the symptoms, laboratory test results, and chest imaging results of COVID-19 patients at the time of the hospital admission and the ambulatory visits after discharge at two university hospitals between July and December 2020.

PATIENTS: A total of 126 COVID-19 patients, including of 88 with mild to moderate disease and 38 with severe to critical disease, were included. The time between symptom onset and the first outpatient visit was 46 days (Interquartile range, 39 to 55).

RESULTS: At the ambulatory visits, 36.5% of patients had at least one symptom. The most frequent symptom was shortness of breath (12.8%), followed by cough (11.1%), and fatigue (8.8%). Of 120 patients with post-discharge laboratory test results, 27 patients (22.5%) had abnormal alanine aminotransferase levels, and 35 patients (29.1%) had lymphocytopenia, including 24 and 27 mild and moderate patients. Of 122 patients with post-discharge chest computed tomography (CT) scans, 105 (83.3%) had abnormal findings. This abnormality was found in both mild to moderate and severe patients.

CONCLUSIONS: Shortness of breath, abnormal liver function test results and chest CT images often persisted for at least one month after discharge, even when symptoms were mild or moderate during hospitalization.}, } @article {pmid36787868, year = {2023}, author = {Zuin, M and Rigatelli, G and Battisti, V and Costola, G and Roncon, L and Bilato, C}, title = {Reply to "Letter to the editor in response to the paper by Zuin et al. 2023".}, journal = {International journal of cardiology}, volume = {376}, number = {}, pages = {26}, pmid = {36787868}, issn = {1874-1754}, } @article {pmid36787802, year = {2023}, author = {Dennis, A and Cuthbertson, DJ and Wootton, D and Crooks, M and Gabbay, M and Eichert, N and Mouchti, S and Pansini, M and Roca-Fernandez, A and Thomaides-Brears, H and Kelly, M and Robson, M and Hishmeh, L and Attree, E and Heightman, M and Banerjee, R and Banerjee, A}, title = {Multi-organ impairment and long COVID: a 1-year prospective, longitudinal cohort study.}, journal = {Journal of the Royal Society of Medicine}, volume = {116}, number = {3}, pages = {97-112}, pmid = {36787802}, issn = {1758-1095}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Quality of Life ; Longitudinal Studies ; }, abstract = {OBJECTIVES: To determine the prevalence of organ impairment in long COVID patients at 6 and 12 months after initial symptoms and to explore links to clinical presentation.

DESIGN: Prospective cohort study.

PARTICIPANTS: Individuals.

METHODS: In individuals recovered from acute COVID-19, we assessed symptoms, health status, and multi-organ tissue characterisation and function.

SETTING: Two non-acute healthcare settings (Oxford and London). Physiological and biochemical investigations were performed at baseline on all individuals, and those with organ impairment were reassessed.

MAIN OUTCOME MEASURES: Primary outcome was prevalence of single- and multi-organ impairment at 6 and 12 months post COVID-19.

RESULTS: A total of 536 individuals (mean age 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post COVID-19); 331 (62%) with organ impairment or incidental findings had follow-up, with reduced symptom burden from baseline (median number of symptoms 10 and 3, at 6 and 12 months, respectively). Extreme breathlessness (38% and 30%), cognitive dysfunction (48% and 38%) and poor health-related quality of life (EQ-5D-5L < 0.7; 57% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single-organ impairment. Single- and multi-organ impairment were present in 69% and 23% at baseline, persisting in 59% and 27% at follow-up, respectively.

CONCLUSIONS: Organ impairment persisted in 59% of 331 individuals followed up at 1 year post COVID-19, with implications for symptoms, quality of life and longer-term health, signalling the need for prevention and integrated care of long COVID.Trial Registration: ClinicalTrials.gov Identifier: NCT04369807.}, } @article {pmid36786887, year = {2023}, author = {Shachar-Lavie, I and Shorer, M and Segal, H and Fennig, S and Ashkenazi-Hoffnung, L}, title = {Mental health among children with long COVID during the COVID-19 pandemic.}, journal = {European journal of pediatrics}, volume = {182}, number = {4}, pages = {1793-1801}, pmid = {36786887}, issn = {1432-1076}, mesh = {Child ; Humans ; Child, Preschool ; Adolescent ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; Mental Health ; Case-Control Studies ; SARS-CoV-2 ; Parents/psychology ; }, abstract = {A growing number of studies report that persons of all ages, infected with SARS-CoV-2, may experience long-term persistent symptoms, known as long COVID (LC) or post COVID-19 condition. This is one of the first studies examining the consequences of LC on children's mental health. In this case-control study, we compared select mental health aspects of 103 children diagnosed with LC to a control group of 113 children uninfected with SARS-COV-2; all 4-18 years old. Both groups were assessed via parents' questionnaires. In comparison to the control group, children with LC exhibited more memory difficulties. However, no group differences emerged in other functional aspects (connection with friends and engagement in physical activities), problems with concentration, or levels of emotional-behavioral problems (externalizing, internalizing, ADHD, and PTSD symptoms). We also found that children with LC had greater exposure to COVID-19-related stressors. Higher levels of parental worries regarding their children's functioning and economic difficulties at home significantly predicted higher levels of children's emotional-behavioral problems and were better predictors than the child's age, social functioning, or LC diagnosis. Conclusion: LC was associated with impairments in some aspects of children's memory which may relate to academic functioning, but not with higher rates of emotional-behavioral problems, thus warranting interventional programs addressing school functioning and cognitive abilities in this population. Additionally, parents' economic stress and worries regarding their child's emotional adjustment during the pandemic, are important factors affecting pandemic-related emotional-behavioral problems among children, regardless of COVID-19 infection, that should be addressed. What is Known: • Children may have long COVID (LC) after being infected with SARS-COV-2. What is New: • LC may be associated to impairments in some aspects of children's memory, as reported by parents. • Parents' economic stress and worries concerning their children's emotional adjustment during the pandemic are associated with more distress in their children.}, } @article {pmid36786877, year = {2023}, author = {ZeinElabdeen, SG and Sherif, A and Kandil, NT and Altabib, AMO and Abdelrashid, MA}, title = {Left atrial longitudinal strain analysis in long Covid-19 syndrome.}, journal = {The international journal of cardiovascular imaging}, volume = {39}, number = {5}, pages = {939-944}, pmid = {36786877}, issn = {1875-8312}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Atrial Fibrillation ; Predictive Value of Tests ; *COVID-19 ; Heart Atria/diagnostic imaging ; *Ventricular Dysfunction, Left ; Disease Progression ; }, abstract = {It is known that during the active course of Coronavirus disease 2019 (COVID-19), myocardial injury has an established pathological base, while its myocardial injury post-recovery is still obscured.The aim of this study was to evaluate the longitudinal left atrial strain (LAS) using speckle tracking echocardiography (STE) in COVID-19-recovered patients who are previously healthy without confounder comorbidities to detect the potential cardiac dysfunction.200 patients were prospectively included and examined 4?12 weeks after recovery from COVID-19 infection. 137 participants with comorbidities or previous history of cardiopulmonary disease were excluded from the analysis. A total of 63 patients who fulfilled our inclusion criteria were recruited into two groups according to thepresence or absence of persistent dyspnoea and exercise intolerance. Clinical, laboratory & comprehensive echocardiographic examinations were done for all. We observed that 31.7% of the previously healthy individuals developed dyspnoea & exercise intolerance post-COVID-19 infection. There were significantly impaired LAS parameters in the symptomatic group (LA reservoir, contraction & conduit strain, 22.7%, -6.6% & -16.1% versus 40%, -12%, and ? 27% in the asymptomatic group with P < 0.000). Only LA reservoir strain and LA stiffness can independently predict the development of dyspnoea & exercise intolerance post-COVID-19 at cut-off values of 30% & 24.5% respectively with a sensitivity of 90% and a specificity of 91%, P < 0.001. These impaired LAS parameters could explain the developed symptoms post-COVID-19 recovery, even before disturbed conventional diastolic echocardiographic parameters.LAS parameters are significantly associated with the developed exertional dyspnoea & exercise intolerance post-COVID-19. LA reservoir strain & LA stiffness could provide a simple, easily available tool that points to early LV diastolic dysfunction and may direct the therapy in this subset of the population.}, } @article {pmid36786618, year = {2023}, author = {Fogh, K and Garred, P and Hansen, CB and Iversen, KK}, title = {Reply to Brandt et al., "Antibodies to Nucleocapsid Are Not Diagnostic for Long COVID".}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0006523}, pmid = {36786618}, issn = {2165-0497}, } @article {pmid36785842, year = {2023}, author = {Zhang, Y and Hu, H and Fokaidis, V and V, CL and Xu, J and Zang, C and Xu, Z and Wang, F and Koropsak, M and Bian, J and Hall, J and Rothman, RL and Shenkman, EA and Wei, WQ and Weiner, MG and Carton, TW and Kaushal, R}, title = {Identifying environmental risk factors for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the recover program.}, journal = {Environmental advances}, volume = {11}, number = {}, pages = {100352}, pmid = {36785842}, issn = {2666-7657}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the association between "exposome"-the totality of environmental exposures and the risk of PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified environmental risk factors for 23 PASC symptoms and conditions from nearly 200 exposome factors. The three domains of exposome include natural environment, built environment, and social environment. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each exposome factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) exposome characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, blood, circulatory, endocrine, and other organ systems. Specific environmental risk factors for each PASC condition and symptom were different across the New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular exposome characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.}, } @article {pmid36785807, year = {2023}, author = {Berends, N}, title = {[Not Available].}, journal = {Nursing}, volume = {29}, number = {1}, pages = {10-13}, doi = {10.1007/s41193-023-0166-z}, pmid = {36785807}, issn = {2468-1431}, } @article {pmid36778263, year = {2023}, author = {Perlis, RH and Santillana, M and Ognyanova, K and Lazer, D}, title = {Correlates of symptomatic remission among individuals with post-COVID-19 condition.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36778263}, support = {R01 GM130668/GM/NIGMS NIH HHS/United States ; RF1 MH132335/MH/NIMH NIH HHS/United States ; }, abstract = {IMPORTANCE: Post-COVID-19 condition (PCC), or long COVID, has become prevalent. The course of this syndrome, and likelihood of remission, has not been characterized.

OBJECTIVE: To quantify the rates of remission of PCC, and the sociodemographic features associated with remission.

DESIGN: 16 waves of a 50-state U.S. non-probability internet survey conducted between August 2020 and November 2022.

SETTING: Population-based.

PARTICIPANTS: Survey respondents age 18 and older.

MAIN OUTCOME AND MEASURE: PCC remission, defined as reporting full recovery from COVID-19 symptoms among individuals who on a prior survey wave reported experiencing continued COVID-19 symptoms beyond 2 months after the initial month of symptoms.

RESULTS: Among 423 survey respondents reporting continued symptoms more than 2 months after acute test-confirmed COVID-19 illness, who then completed at least 1 subsequent survey, mean age was 53.7 (SD 13.6) years; 293 (69%) identified as women, and 130 (31%) as men; 9 (2%) identified as Asian, 29 (7%) as Black, 13 (3%) as Hispanic, 15 (4%) as another category including Native American or Pacific Islander, and the remaining 357 (84%) as White. Overall, 131/423 (31%) of those who completed a subsequent survey reported no longer being symptomatic. In Cox regression models, male gender, younger age, lesser impact of PCC symptoms at initial visit, and infection when the Omicron strain predominated were all statistically significantly associated with greater likelihood of remission; presence of 'brain fog' or shortness of breath were associated with lesser likelihood of remission.

CONCLUSIONS AND RELEVANCE: A minority of individuals reported remission of PCC symptoms, highlighting the importance of efforts to identify treatments for this syndrome or means of preventing it.}, } @article {pmid36776887, year = {2023}, author = {Udoakang, AJ and Djomkam Zune, AL and Tapela, K and Nganyewo, NN and Olisaka, FN and Anyigba, CA and Tawiah-Eshun, S and Owusu, IA and Paemka, L and Awandare, GA and Quashie, PK}, title = {The COVID-19, tuberculosis and HIV/AIDS: Ménage à Trois.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1104828}, pmid = {36776887}, issn = {1664-3224}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/P028071/1/MRC_/Medical Research Council/United Kingdom ; /CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Acquired Immunodeficiency Syndrome/epidemiology ; *COVID-19 ; HIV ; *Coinfection/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Tuberculosis/diagnosis ; }, abstract = {In December 2019, a novel pneumonic condition, Coronavirus disease 2019 (COVID- 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in China and spread globally. The presentation of COVID-19 is more severe in persons with underlying medical conditions such as Tuberculosis (TB), Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and other pneumonic conditions. All three diseases are of global concern and can significantly affect the lungs with characteristic cytokine storm, immunosuppression, and respiratory failure. Co-infections of SARS-CoV-2 with HIV and Mycobacterium tuberculosis (Mtb) have been reported, which may influence their pathogenesis and disease progression. Pulmonary TB and HIV/AIDS patients could be more susceptible to SARS-CoV-2 infection leading to lethal synergy and disease severity. Therefore, the biological and epidemiological interactions of COVID-19, HIV/AIDS, and TB need to be understood holistically. While data is needed to predict the impact of the COVID-19 pandemic on these existing diseases, it is necessary to review the implications of the evolving COVID-19 management on HIV/AIDS and TB control, including therapy and funding. Also, the impact of long COVID on patients, who may have this co-infection. Thus, this review highlights the implications of COVID-19, HIV/AIDS, and TB co-infection compares disease mechanisms, addresses growing concerns, and suggests a direction for improved diagnosis and general management.}, } @article {pmid36776879, year = {2023}, author = {Jeon, K and Kim, Y and Kang, SK and Park, U and Kim, J and Park, N and Koh, J and Shim, MS and Kim, M and Rhee, YJ and Jeong, H and Lee, S and Park, D and Lim, J and Kim, H and Ha, NY and Jo, HY and Kim, SC and Lee, JH and Shon, J and Kim, H and Jeon, YK and Choi, YS and Kim, HY and Lee, WW and Choi, M and Park, HY and Park, WY and Kim, YS and Cho, NH}, title = {Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1101808}, pmid = {36776879}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Kinetics ; Post-Acute COVID-19 Syndrome ; Inflammation ; Inflammation Mediators ; Interferon-alpha ; }, abstract = {INTRODUCTION: Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive.

METHODS: Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients.

RESULTS: Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients.

DISCUSSION: Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.}, } @article {pmid36776093, year = {2023}, author = {Gyllensten, K and Holm, A and Sandén, H}, title = {Workplace factors that promote and hinder work ability and return to work among individuals with long-term effects of COVID-19: A qualitative study.}, journal = {Work (Reading, Mass.)}, volume = {75}, number = {4}, pages = {1101-1112}, pmid = {36776093}, issn = {1875-9270}, mesh = {Humans ; *COVID-19 ; Return to Work ; Post-Acute COVID-19 Syndrome ; Work Capacity Evaluation ; SARS-CoV-2 ; Workplace/psychology ; }, abstract = {BACKGROUND: Long COVID is defined by the persistence of physical and/or psychological and cognitive symptoms debuting after SARS-CoV-2 infection. Individuals affected describe impairing and debilitating symptoms sometimes making it difficult to take part in work and social life. Long COVID is likely to have an impact on the work force.

OBJECTIVE: The aim of the study was to explore workplace factors that promote and hinder work ability and return to work among individuals with long-term effects of COVID-19.

METHODS: A qualitative design was used. Data were collected by semi-structured focus group interviews and analysed using inductive thematic analysis. To increase trustworthiness, several researchers were involved in the data collection and analysis. Five focus group interviews were conducted with individuals suffering from long-term effects from COVID-19 affecting their work ability. In total, 19 individuals participated in the study, and all were working at least 50 per cent at the time of recruitment.

RESULTS: Five main themes emerged from the analysis: Communication and support, Possibilities to adjust work, Acceptance of new limitations, Increased need for recovery from work and Lack of knowledge and understanding of the effects of Covid.

CONCLUSION: The results suggested that it is useful to facilitate communication, support and work adjustments for individuals suffering from Long COVID. It is also important to accept limitations and fluctuations in work ability and encourage recovery during and after work.}, } @article {pmid36775065, year = {2023}, author = {Perisse, A and De Cacqueray, F and Delarbre, D and Marsaa, H and Bergmann, C and Da Silva, V and Bronstein, A and Paleiron, N and Menoud, N and Cobola, J and Verret, C and Mayet, A and Bylicki, O}, title = {Symptoms of Long-COVID 1-Year after a COVID-19 outbreak among sailors on a French aircraft carrier.}, journal = {Infectious diseases now}, volume = {53}, number = {4}, pages = {104673}, pmid = {36775065}, issn = {2666-9919}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Military Personnel ; Prospective Studies ; Disease Outbreaks ; Aircraft ; }, abstract = {OBJECTIVES: While persistent symptoms have been reported after the coronavirus disease-2019 (COVID-19), long-term data on outpatients with mild COVID-19 are lacking. The objective was to describe symptoms persisting for 12 months.

METHODS: This prospective cohort study on 1767 sailors of an aircraft carrier in which a Covid-19 outbreak occurred during a mission in April 2020 described predefined self-reported symptoms of Long-COVID at 6, 9 and 12 months. Logistic-regression analyses were used to identify correlates for Long-COVID at months 6, 9 and 12.

RESULTS: Among the 641 participants, 619 (35%) completed at least one follow-up questionnaire (413 COVID-positive and 206 COVID-negative). Symptoms of Long-COVID were reported by 53.7%, 55.2% and 54.3% of COVID-positive participants vs 31.2%, 23.3% and 40.0% in COVID-negative patients, at 6 (p <.002), 9 (p <.002) and 12 months (p =.13), respectively. The most frequent symptoms reported were concentration and memory difficulties, asthenia and sleep disorders.

CONCLUSION: In this study more than half of COVID-positive outpatients reported persistent symptoms up to 12 months post-quarantine. These findings suggests that all patients, including those with mild disease, can be affected by Long-COVID. A lack of difference at 12 months with COVID-negative patienys prompts caution. The symptoms of Long-COVID are so non-specific that they may be viewed as the consequence of multiple intercurrent factors.}, } @article {pmid36774419, year = {2023}, author = {Nascimento, TCDC and do Valle Costa, L and Ruiz, AD and Ledo, CB and Fernandes, VPL and Cardoso, LF and Junior, JMV and Saretta, R and Kalil-Filho, R and Drager, LF}, title = {Vaccination status and long COVID symptoms in patients discharged from hospital.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2481}, pmid = {36774419}, issn = {2045-2322}, mesh = {Male ; Humans ; Female ; Adult ; Middle Aged ; Aged ; *COVID-19/epidemiology/prevention & control ; Patient Discharge ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Hospitalization ; Hospitals ; Intensive Care Units ; Vaccination ; }, abstract = {Effective vaccination against coronavirus mitigates the risk of hospitalisation and mortality; however, it is unclear whether vaccination status influences long COVID symptoms in patients who require hospitalisation. The available evidence is limited to outpatients with mild disease. Here, we evaluated 412 patients (age: 60 ± 16 years, 65% males) consecutively admitted to two Hospitals in Brazil due to confirmed coronavirus disease 2019 (COVID-19). Compared with patients with complete vaccination (n = 185) before infection or hospitalisation, those with no or incomplete vaccination (n = 227) were younger and had a lower frequency of several comorbidities. Data during hospitalisation revealed that the no or incomplete vaccination group required more admissions to the intensive care unit (ICU), used more corticosteroids, and had higher rates of pulmonary embolism or deep venous thrombosis than the complete vaccination group. Ninety days after hospital discharge, patients with no or incomplete vaccination presented a higher frequency of symptoms (≥ 1) than patients with complete vaccination (40 vs. 27%; p = 0.013). After adjusting for confounders, no or incomplete vaccination (odds ratio [OR] 1.819; 95% confidence interval [CI] 1.175-2.815), female sex (OR 2.435; 95% CI 1.575-3.764) and ICU admission during hospitalisation (OR 1.697; 95% CI 1.062-2.712) were independently associated with ≥ 1 symptom 90 days after hospital discharge. In conclusion, even in patients with severe COVID-19, vaccination mitigates the probability of long COVID symptoms.}, } @article {pmid36774332, year = {2023}, author = {Watanabe, A and Iwagami, M and Yasuhara, J and Takagi, H and Kuno, T}, title = {Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis.}, journal = {Vaccine}, volume = {41}, number = {11}, pages = {1783-1790}, pmid = {36774332}, issn = {1873-2518}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.

METHODS: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.

RESULTS: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.

CONCLUSIONS: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.}, } @article {pmid36773054, year = {2023}, author = {Ferrara, F and Zovi, A and Masi, M and Langella, R and Trama, U and Boccellino, M and Vitiello, A}, title = {Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {396}, number = {7}, pages = {1583-1589}, pmid = {36773054}, issn = {1432-1912}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; tau Proteins ; Pandemics ; SARS-CoV-2 ; Fatigue ; }, abstract = {Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.}, } @article {pmid36769845, year = {2023}, author = {Colzato, LS and Elmers, J and Beste, C and Hommel, B}, title = {A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769845}, issn = {2077-0383}, abstract = {Long COVID, the postviral disorder caused by COVID-19, is expected to become one of the leading causes of disability in Europe. The cognitive consequences of long COVID have been described as "brain fog" and characterized by anxiety and depression, and by cognitive deficits. Long COVID is assumed to be a complex condition arising from multiple causes, including persistent brainstem dysfunction and disrupted vagal signaling. We recommend the potential application of auricular transcutaneous vagus nerve stimulation (atVNS) as an ADD-ON instrument to compensate for the cognitive decline and to ameliorate affective symptoms caused by long COVID. This technique enhances vagal signaling by directly activating the nuclei in the brainstem, which are hypoactive in long COVID to enhance mood and to promote attention, memory, and cognitive control-factors affected by long COVID. Considering that atVNS is a non-pharmacological intervention, its ADD-ON to standard pharmaceutical agents will be useful for non-responders, making of this method a suitable tool. Given that atVNS can be employed as an ecological momentary intervention (EMI), we outline the translational advantages of atVNS in the context of accelerating the cognitive and affective recovery from long COVID.}, } @article {pmid36769807, year = {2023}, author = {Chourasia, P and Goyal, L and Kansal, D and Roy, S and Singh, R and Mahata, I and Sheikh, AB and Shekhar, R}, title = {Risk of New-Onset Diabetes Mellitus as a Post-COVID-19 Condition and Possible Mechanisms: A Scoping Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769807}, issn = {2077-0383}, abstract = {Long-term effects of COVID-19 are becoming more apparent even as the severity of acute infection is decreasing due to vaccinations and treatment. In this scoping review, we explored the current literature for the relationship between COVID-19 infection and new-onset diabetes mellitus four weeks after acute infection. We systematically searched the peer-reviewed literature published in English between 1 January 2020 and 31 August 2022 to study the risk of new-onset diabetes mellitus post-COVID-19 infection. This scoping review yielded 11 articles based on our inclusion and exclusion criteria. Except for one, all studies suggested an increased risk of new-onset diabetes mellitus 4 weeks after acute infection. This risk appears most in the first six months after the acute COVID-19 infection and seems to increase in a graded fashion based on the severity of the initial COVID-19 infection. Our review suggests a possible association of new-onset diabetes mellitus 4 weeks after acute COVID-19 infection. Since the severity of COVID-19 infection is associated with the development of post-infectious diabetes, vaccination that reduces the severity of acute COVID-19 infection might help to reduce the risk of post-COVID-19 diabetes mellitus. More studies are needed to better understand and quantify the association of post-COVID-19 conditions with diabetes and the role of vaccination in influencing it.}, } @article {pmid36769425, year = {2023}, author = {Rodriguez-Blanco, C and Bernal-Utrera, C and Anarte-Lazo, E and Gonzalez-Gerez, JJ and Saavedra-Hernandez, M}, title = {A 14-Day Therapeutic Exercise Telerehabilitation Protocol of Physiotherapy Is Effective in Non-Hospitalized Post-COVID-19 Conditions: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769425}, issn = {2077-0383}, support = {"Research and Development in Advanced Physiotherapy in patients affected by post-COVID-19//Fisiosur i+D/ ; }, abstract = {The emergence of COVID-19 has led to serious public health problems. Now that the acute phase of the pandemic has passed, new challenges have arisen in relation to this disease. The post-COVID-19 conditions are a priority for intervention, as months after the onset of the disease, they continue to present symptoms, especially physical and respiratory symptoms. Our aim is to test the efficacy of a fourteen-day telerehabilitation program of respiratory and strength exercises in people with post-COVID-19 conditions. For this purpose, a randomized controlled trial was generated in which data from 48 patients were analyzed using the BS, 30STSTST, MD12, VAFS, and 6MWT tests. The obtained results showed the benefit of the intervention in generating great results with respect to the control group.}, } @article {pmid36769389, year = {2023}, author = {Van Wambeke, E and Bezler, C and Kasprowicz, AM and Charles, AL and Andres, E and Geny, B}, title = {Two-Years Follow-Up of Symptoms and Return to Work in Complex Post-COVID-19 Patients.}, journal = {Journal of clinical medicine}, volume = {12}, number = {3}, pages = {}, pmid = {36769389}, issn = {2077-0383}, abstract = {INTRODUCTION: Many COVID-19 patients present with severe long-lasting symptoms. They might benefit from a coordination team to manage such complex situations, but late efficacy still needs to be determined.

POPULATION AND METHODS: Out of 105 contacts, 45 patients had two phone consultations separated by personalized support 15 and 22 months, respectively, after COVID infection. Self-reported symptoms, feelings of improvement and ability to return to work allowed us to determine the efficacy of the therapeutic strategy proposed.

RESULTS: Unlike what was expected, many post-COVID-19 patients directly contacted the coordination team and had significant pre-existing comorbidities. Despite exercise, respiratory, olfactory rehabilitations, cognition/speech therapy and/or psychological support, the more frequent self-reported symptoms (fatigue, neurocognitive disorders, muscles and joint pain) did not resolve. However, dyspnea, anxiety and chest pain were significantly reduced. Finally, 2/3 of the patients felt some degree of improvement and returned to work either partially or fully, but 1/3 remained complaining of symptoms and out of work as late as 22 months after COVID occurrence. All patients greatly appreciated the second phone consultation.

CONCLUSIONS: In such complex situations, besides early and adapted rehabilitations and psychological help allowing better symptom management, relatively simple actions such as a phone call might be very useful to reduce patients' feelings of abandonment.}, } @article {pmid36769057, year = {2023}, author = {Lennol, MP and Ashton, NJ and Moreno-Pérez, O and García-Ayllón, MS and Ramos-Rincon, JM and Andrés, M and León-Ramírez, JM and Boix, V and Gil, J and Blennow, K and Merino, E and Zetterberg, H and Sáez-Valero, J}, title = {Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769057}, issn = {1422-0067}, mesh = {Humans ; *Angiotensin-Converting Enzyme 2/metabolism ; *COVID-19/metabolism ; SARS-CoV-2 ; Neurons/metabolism ; Neurofilament Proteins ; Biomarkers/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; }, abstract = {The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or "long COVID"), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms.}, } @article {pmid36767932, year = {2023}, author = {Tauekelova, AT and Kalila, Z and Bakhtiyar, A and Sautbayeva, Z and Len, P and Sailybayeva, A and Khamitov, S and Kadroldinova, N and Barteneva, NS and Bekbossynova, MS}, title = {Association of Lung Fibrotic Changes and Cardiological Dysfunction with Comorbidities in Long COVID-19 Cohort.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {3}, pages = {}, pmid = {36767932}, issn = {1660-4601}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Diabetes Mellitus, Type 2/complications ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; *Hypertension/complications ; Lung ; }, abstract = {Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID-19 and its comorbidities have not been established. Methods. In total, 312 patients with long COVID-19 from 21 primary care centers were included in the study. At the six-month follow-up, their lung function was assessed by computerized tomography (CT) and spirometry, whereas cardiac function was assessed by elec-trocardiogram (ECG), Holter ECG, echocardiography, 24 h blood pressure monitoring, and a six-minute walk test (6MWT). Results. Of the 312 persons investigated, significantly higher sys-tolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP were revealed in participants with hypertension or type 2 diabetes. Left ventricular diastolic dysfunc-tion was more frequently present in patients with hypertension. The most common registered CT abnormalities were fibrotic changes (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Among the tested biochemical parameters, three associations were found in long COVID-19 patients with hypertension but not diabetes: increased hemoglobin, fibrinogen, and ferritin. Nine patients had persisting IgM antibodies to SARS-CoV-2. Conclusions. We demon-strated a strong association between signs of cardiac dysfunction and lung fibrotic changes with comorbidities in a cohort of long COVID-19 subjects.}, } @article {pmid36767195, year = {2023}, author = {Ho, FF and Xu, S and Kwong, TMH and Li, AS and Ha, EH and Hua, H and Liong, C and Leung, KC and Leung, TH and Lin, Z and Wong, SY and Pan, F and Chung, VCH}, title = {Prevalence, Patterns, and Clinical Severity of Long COVID among Chinese Medicine Telemedicine Service Users: Preliminary Results from a Cross-Sectional Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {3}, pages = {}, pmid = {36767195}, issn = {1660-4601}, mesh = {Male ; Humans ; Female ; Middle Aged ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Prevalence ; Medicine, Chinese Traditional ; *Telemedicine ; }, abstract = {INTRODUCTION: The emergence and persistence of symptoms after acute COVID-19 is expected to become a major burden on healthcare systems. We assessed the features of the post-COVID-19 Syndrome (Long COVID) burden in a cohort of COVID-19 patients during the fifth major wave in Hong Kong.

METHODS: A cross-sectional study of 135 patients with confirmed COVID-19 from Feb to Apr 2022 who utilized traditional Chinese medicine telemedicine services was conducted. The COVID-19 Yorkshire Rehabilitation Scale was administered using an online survey 12 weeks after the COVID-19 infection. Prevalence of symptom severity and functional impairments were assessed to identify burdens and patterns. The correlation between symptom severity, functional impairments, patient characteristics, and overall health was evaluated.

RESULTS: The mean age was 46.8 years, with 46 (34.1%) males. Symptoms, functional impairments, and overall health worsened significantly when compared to the status prior to the infection. More than 50% reported the following sequelae 12 weeks after the acute infection: breathlessness, laryngeal or airway complications, fatigue, weakness, sleep, cognition, and anxiety. The presence of a single symptom or functional impairment significantly correlated with at least seven other problems positively, except for pain. Severity tended to be higher among vulnerable groups, including those who were chronic disease patients, older, less well educated, female, or had incomplete COVID-19 vaccinations.

CONCLUSIONS: Long COVID is a significant healthcare burden among telemedicine users in Hong Kong, with complex needs for symptom and functional impairment management. Designing relevant health and rehabilitation services tailored to the needs of these patients is warranted.}, } @article {pmid36766859, year = {2023}, author = {Maiorana, NV and Aiello, EN and Poletti, B and Carusi, F and De Sandi, A and Guidetti, M and Prandin, R and Marceglia, S and Ticozzi, N and Silani, V and Priori, A and Ferrucci, R}, title = {Relationship between Reaction Times and Post-COVID-19 Symptoms Assessed by a Web-Based Visual Detection Task.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {3}, pages = {}, pmid = {36766859}, issn = {2227-9032}, abstract = {Long-COVID is a clinical condition in which patients affected by SARS-CoV-2 usually report a wide range of physical and cognitive symptoms from 3 to 6 months after the infection recovery. The aim of the current study was to assess the link between self-reported long-COVID symptoms and reaction times (RTs) in a self-administered Visual Detection Task (VDT) in order to identify the predictor symptoms of the slowing in reaction times to determine attention impairment. In total, 362 participants (age (mean ± S.D.: 38.56 ± 13.14); sex (female-male: 73.76-26.24%)) responded to a web-based self-report questionnaire consisting of four sections: demographics, disease-related characteristics, and medical history questions. The final section consisted of a 23 item 5-point Likert-scale questionnaire related to long-term COVID-19 symptoms. After completing the questionnaire, subjects performed a VDT on a tablet screen to assess reaction times (RTs). An exploratory factorial analysis (EFA) was performed on the 23 long-COVID symptom questions, identifying 4 factors (cognition, behavior, physical condition, presence of anosmia and/or ageusia). The most important predictors of RTs were cognition and physical factors. By dissecting the cognitive and physical factors, learning, visual impairment, and headache were the top predictors of subjects' performance in the VDT. Long-COVID subjects showed higher RTs in the VDT after a considerable time post-disease, suggesting the presence of an attention deficit disorder. Attention impairment due to COVID-19 can be due to the presence of headaches, visual impairments, and the presence of cognitive problems related to the difficulty in learning new activities. The link between the slowing of reaction times and physical and cognitive symptoms post-COVID-19 suggests that attention deficit disorder is caused by a complex interaction between physical and cognitive symptoms. In addition, the study provides evidence that RTs in a VDT represent a reliable measure to detect the presence of long-COVID neurological sequelae.}, } @article {pmid36766599, year = {2023}, author = {Shrestha, AB and Mehta, A and Pokharel, P and Mishra, A and Adhikari, L and Shrestha, S and Yadav, RS and Khanal, S and Sah, R and Nowrouzi-Kia, B and Padhi, BK and Chattu, VK}, title = {Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {36766599}, issn = {2075-4418}, abstract = {(1) Background: Long COVID syndrome is a significant cause of morbidity in COVID-19 patients who remain symptomatic with varied clinical presentations beyond three weeks. Furthermore, the relevance of considering cardiovascular outcomes in post-COVID-19 syndrome is important in the current COVID-19 pandemic; (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review and meta-analysis. Systematic searches were conducted from multiple databases without language restrictions until October 8, 2022, to find studies evaluating cardiovascular outcomes such as arrhythmias, myocardium and pericardium diseases, coronary vessel disease, and thromboembolic disorders in post-COVID cases. The pooled odds ratio (OR), and standard mean difference (SMD) with their corresponding 95% confidence intervals (CI) were computed to find the association; (3) Results: Altogether, seven studies with a total of 8,126,462 (cases: 1,321,305; controls: 6,805,157) participants were included in the meta-analysis. Pooled odds ratios of cardiovascular outcomes were significantly higher in post-COVID cases (OR > 1, p < 0.05) than in controls. However, the mortality (OR: 4.76, p = 0.13), and heart rate variability (SMD: -0.06, p = 0.91) between cases and controls were not statistically significant; (4) Conclusions: Significant cardiovascular sequelae in long COVID syndrome highlight the importance of careful cardiac monitoring of COVID-19 patients in the post-COVID phase to address cardiovascular complications as soon as possible; larger-scale prospective studies are required for accurate estimation.}, } @article {pmid36764682, year = {2023}, author = {, and , and , }, title = {As a doctor with long covid, I feel abandoned by the NHS.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {337}, doi = {10.1136/bmj.p337}, pmid = {36764682}, issn = {1756-1833}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; State Medicine ; *COVID-19/epidemiology ; *Physicians ; Emotions ; }, } @article {pmid36762927, year = {2023}, author = {Manu, P}, title = {Ivermectin and the Emergence of Long COVID.}, journal = {American journal of therapeutics}, volume = {30}, number = {2}, pages = {e145}, doi = {10.1097/MJT.0000000000001607}, pmid = {36762927}, issn = {1536-3686}, mesh = {Humans ; *Ivermectin/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36762752, year = {2023}, author = {Fajloun, Z and Abi Khattar, Z and Kovacic, H and Legros, C and Sabatier, JM}, title = {SIBO: The Trail of a "New" Human Pathology Associated with Multiple Severe and Disabling COVID-19 and Long COVID Symptoms or Induced by the Anti-COVID-19 Vaccine.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {4}, pages = {e100223213593}, doi = {10.2174/1871526523666230210162334}, pmid = {36762752}, issn = {2212-3989}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; *COVID-19/prevention & control ; }, } @article {pmid36761395, year = {2023}, author = {Taruffi, L and Muccioli, L and Mitolo, M and Ferri, L and Descovich, C and Mazzoni, S and Michelucci, R and Lodi, R and Liguori, R and Cortelli, P and Tonon, C and Bisulli, F}, title = {Neurological Manifestations of Long COVID: A Single-Center One-Year Experience.}, journal = {Neuropsychiatric disease and treatment}, volume = {19}, number = {}, pages = {311-319}, pmid = {36761395}, issn = {1176-6328}, abstract = {PURPOSE: We report our single-center experience on the neurological manifestations of long COVID.

PATIENTS AND METHODS: This is a retrospective observational study. All consecutive patients referred to the neurological long COVID outpatient clinic of our institute from January 21 2021 to December 9 2021 underwent a general neurological objective examination. Treatments and investigations (brain MRI, neuropsychological evaluation, or others) were prescribed on an individual basis as per standard clinical practice. A follow-up visit was performed when appropriate. Descriptive statistics were presented as absolute and relative frequencies for categorical variables and as means, median, and ranges for continuous variables.

RESULTS: One hundred and three patients were visited (mean age 50.5 ±36 years, 62 females). The average time from acute COVID-19 infection to the first visit to our outpatient clinic was 243 days. Most patients presented with a mild form of acute COVID-19, with only 24 cases requiring hospitalization. The neurological symptoms mostly (n=70/103, 68%) started during the acute phase (before a negative swab for SARS-CoV-2). The most frequent acute manifestations reported, which lately became persistent, were fatigue (n=58/103, 56%), olfactory/taste dysfunction (n=58/103, 56%), headache (n=47/103, 46%), cognitive disorders (n=46/103, 45%), sleep disorders (n=30/103, 29%), sensitivity alterations (n=29/103, 28%), and dizziness (n=7/103, 7%). Tremor was also reported (n=8/103, 7%). Neuropsychological evaluation was performed in 30 patients and revealed alterations in executive functions (n=6/30, 20%), memory (n=11/30, 37%), with pathological depressive (n=9/30, 30%) and anxiety (n=8/30, 27%) scores. Brain MRIs have been performed in 41 cases, revealing nonspecific abnormal findings only in 4 cases. Thirty-six patients underwent a follow-up, where a general improvement was observed but rarely (n=2/36) a complete recovery.

CONCLUSION: The majority of patients presenting persistent neurological symptoms (most frequently fatigue, cognitive disorders, and olfactory dysfunctions) developed a previous mild form of COVID-19. Further studies are required to develop therapeutic strategies.}, } @article {pmid36760005, year = {2023}, author = {Fernández-Alonso, V and Rodríguez-Fernández, S and Secadas-Rincón, L and Pérez-Gómez, M and Moro-Tejedor, MN and Salcedo, M}, title = {Resilience After COVID-19: A Descriptive, Cross-Sectional Study.}, journal = {Clinical nursing research}, volume = {32}, number = {3}, pages = {618-628}, pmid = {36760005}, issn = {1552-3799}, mesh = {Adult ; Humans ; *COVID-19 ; Cross-Sectional Studies ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *Resilience, Psychological ; Depression ; Anxiety ; }, abstract = {The main purpose of this study was to examine the relationship between resilience and health-related quality of life in patients following COVID-19 disease among those with and without lingering symptoms. The study design is descriptive and cross-sectional. Participants (n = 97) were adults who had earlier contracted COVID-19 disease and were in post-infection status between July and October 2020. Participants completed the following instruments: Connor-Davidson Resilience Scale, Short-Form 12-item Health Survey, and Hospital Anxiety and Depression Scale. Approximately 35% post-COVID-19 patients had a low level of resilience. The impact on the health status and resilience of those who had reported symptoms after 6 months was also significant. Age and depression had a significant impact on level of resilience. This relationship can affect patient recovery and negatively impact the ability to cope with COVID-19 disease. It is necessary to implement specialized training for clinicians on the effects of long-term COVID-19 to improve patient care. Long COVID symptoms might manifest months after an acute COVID-19 illness; clinicians who can confirm patient reports of these symptoms may help patients recover and become more resilient.}, } @article {pmid36759161, year = {2023}, author = {Ladlow, P and Holdsworth, DA and O'Sullivan, O and Barker-Davies, RM and Houston, A and Chamley, R and Rogers-Smith, K and Kinkaid, V and Kedzierski, A and Naylor, J and Mulae, J and Cranley, M and Nicol, ED and Bennett, AN}, title = {Exercise tolerance, fatigue, mental health, and employment status at 5 and 12 months following COVID-19 illness in a physically trained population.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {134}, number = {3}, pages = {622-637}, pmid = {36759161}, issn = {1522-1601}, mesh = {Humans ; *COVID-19 ; Exercise Tolerance ; SARS-CoV-2 ; Fatigue ; Dyspnea ; Employment ; Mental Fatigue ; }, abstract = {Failure to recover following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may have a profound impact on individuals who participate in high-intensity/volume exercise as part of their occupation/recreation. The aim of this study was to describe the longitudinal cardiopulmonary exercise function, fatigue, and mental health status of military-trained individuals (up to 12-mo postinfection) who feel recovered, and those with persistent symptoms from two acute disease severity groups (hospitalized and community-managed), compared with an age-, sex-, and job role-matched control. Eighty-eight participants underwent cardiopulmonary functional tests at baseline (5 mo following acute illness) and 12 mo; 25 hospitalized with persistent symptoms (hospitalized-symptomatic), 6 hospitalized and recovered (hospitalized-recovered); 28 community-managed with persistent symptoms (community-symptomatic); 12 community-managed, now recovered (community-recovered), and 17 controls. Cardiopulmonary exercise function and mental health status were comparable between the 5 and 12-mo follow-up. At 12 mo, symptoms of fatigue (48% and 46%) and shortness of breath (SoB; 52% and 43%) remain high in hospitalized-symptomatic and community-symptomatic groups, respectively. At 12 mo, COVID-19-exposed participants had a reduced capacity for work at anaerobic threshold and at peak exercise levels of deconditioning persist, with many individuals struggling to return to strenuous activity. The prevalence considered "fully fit" at 12 mo was lowest in symptomatic groups (hospitalized-symptomatic, 4%; hospitalized-recovered, 50%; community-symptomatic, 18%; community-recovered, 82%; control, 82%) and 49% of COVID-19-exposed participants remained medically nondeployable within the British Armed Forces. For hospitalized and symptomatic individuals, cardiopulmonary exercise profiles are consistent with impaired metabolic efficiency and deconditioning at 12 mo postacute illness. The long-term deployability status of COVID-19-exposed military personnel is uncertain.NEW & NOTEWORTHY Subjective exercise limiting symptoms such as fatigue and shortness of breath reduce but remain prevalent in symptomatic groups. At 12 mo, COVID-19-exposed individuals still have a reduced capacity for work at the anaerobic threshold (which best predicts sustainable intensity), despite oxygen uptake comparable to controls. The prevalence of COVID-19-exposed individuals considered "medically non-deployable" remains high at 47%.}, } @article {pmid36759021, year = {2023}, author = {Faux-Nightingale, A and Burton, C and Twohig, H and Blagojevic-Bucknall, M and Carroll, W and Chew-Graham, CA and Dunn, K and Gilchrist, F and Helliwell, T and Lawton, O and Lawton, S and Mallen, C and Saunders, B and van der Windt, D and Welsh, V}, title = {Symptom patterns and life with post-acute COVID-19 in children aged 8-17 years: a mixed-methods study protocol.}, journal = {BJGP open}, volume = {7}, number = {2}, pages = {}, pmid = {36759021}, issn = {2398-3795}, abstract = {BACKGROUND: While there is a substantial body of knowledge about acute COVID-19, less is known about long-COVID, where symptoms continue beyond 4 weeks.

AIM: To describe longer-term effects of COVID-19 infection in children and young people (CYP) and identify their needs in relation to long-COVID.

DESIGN & SETTING: This study comprises an observational prospective cohort study and a linked qualitative study, identifying participants aged 8-17 years in the West Midlands of England.

METHOD: CYP will be invited to complete online questionnaires to monitor incidences and symptoms of COVID-19 over a 12-month period. CYP who have experienced long-term effects of COVID will be invited to interview, and those currently experiencing symptoms will be asked to document their experiences in a diary. Professionals who work with CYP will be invited to explore the impact of long-COVID on the wider experiences of CYP, in a focus group. Descriptive statistics will be used to describe the incidence and rates of resolution of symptoms, and comparisons will be made between exposed and non-exposed groups. Logistic regression models will be used to estimate associations between candidate predictors and the development of long-COVID, and linear regression will be used to estimate associations between candidate predictors. Qualitative data will be analysed thematically using the constant comparison method.

CONCLUSION: This study will describe features and symptoms of long-COVID and explore the impact of long-COVID within the lives of CYP and their families, to provide better understanding of long-COVID and inform clinical practice.}, } @article {pmid36758864, year = {2023}, author = {Carbone, RG and Puppo, F}, title = {Pericarditis in long COVID-19.}, journal = {International journal of cardiology}, volume = {376}, number = {}, pages = {156}, pmid = {36758864}, issn = {1874-1754}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Pericarditis ; *Myocarditis ; Vaccination ; }, } @article {pmid36757946, year = {2023}, author = {Epsi, NJ and Powers, JH and Lindholm, DA and Mende, K and Malloy, A and Ganesan, A and Huprikar, N and Lalani, T and Smith, A and Mody, RM and Jones, MU and Bazan, SE and Colombo, RE and Colombo, CJ and Ewers, EC and Larson, DT and Berjohn, CM and Maldonado, CJ and Blair, PW and Chenoweth, J and Saunders, DL and Livezey, J and Maves, RC and Sanchez Edwards, M and Rozman, JS and Simons, MP and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and , }, title = {A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms.}, journal = {PloS one}, volume = {18}, number = {2}, pages = {e0281272}, pmid = {36757946}, issn = {1932-6203}, support = {Y01 AI005072/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Interleukin-6 ; Phenotype ; Hospitalization ; Machine Learning ; }, abstract = {BACKGROUND: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles.

METHODS: 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations.

RESULTS: We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 ("Nasal cluster") is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 ("Sensory cluster") is highly correlated with loss of smell or taste, and cluster 3 ("Respiratory/Systemic cluster") is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01).

CONCLUSIONS: We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.}, } @article {pmid36757300, year = {2023}, author = {Yilmaz Gokmen, G and Durmaz, D and Demir, C and Yilmaz, FN}, title = {Determining Post-COVID-19 Symptoms and Rehabilitation Needs in Hospitalized and Nonhospitalized COVID-19 Survivors with Tele-Assessment Methods.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {29}, number = {9}, pages = {1312-1323}, doi = {10.1089/tmj.2022.0349}, pmid = {36757300}, issn = {1556-3669}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Myalgia ; Survivors/psychology ; Fatigue ; }, abstract = {Objectives: This study aimed to evaluate the post-COVID-19 symptoms, the severity of symptoms, and functional capacities seen in hospitalized and nonhospitalized COVID-19 survivors according to time periods (total 6, 1-3, and 3-6 months) by tele-assessment methods and to predict the need for periodic rehabilitation of COVID-19 survivors. Methods: Three hundred ninety-four COVID-19 survivors (50.18 ± 15.14 years) who were between 1 and 6 months after PCR(+) were included in the study, and their ongoing symptoms and the severity of these symptoms (0-10 points) were assessed with COVID-19 Yorkshire Rehabilitation Screening (C19-YRS) Tool, and the 30-s Chair Stand Test (CST) was applied by tele-assessment methods. Results: In hospitalized and nonhospitalized survivors of COVID-19, 87% experienced at least one symptom within the first 6 months. The most prevalent symptoms were anxiety (47.7%), fatigue (46.7%), and muscle pain (45.7%). The most common symptom in the nonhospitalized group was fatigue (52.6%), whereas anxiety was 46.8% in the hospitalized group. The 30-s CST score of the nonhospitalized group was significantly higher than the hospitalized group (p < 0.001). Conclusions: In the first 6 months post-COVID-19, musculoskeletal problems, anxiety, fatigue, and muscle pain were observed to be the most prevalent symptoms, regardless of time, in hospitalized and nonhospitalized survivors. There was a serious decrease in their functional capacity. Priority should be given to psychiatric, cardiopulmonary, and musculoskeletal rehabilitation in post-COVID-19. Inclusion of hospitalized/nonhospitalized COVID-19 survivors in a comprehensive rehabilitation program tailored to their needs by following a comprehensive tele-assessment by a multidisciplinary team will reduce the "long COVID-19 syndrome." ClinicalTrials.gov Registration Number: NCT04900441.}, } @article {pmid36754974, year = {2023}, author = {Abou-Hamdan, M and Saleh, R and Mani, S and Dournaud, P and Metifiot, M and Blondot, ML and Andreola, ML and Abdel-Sater, F and De Reggi, M and Gressens, P and Laforge, M}, title = {Potential antiviral effects of pantethine against SARS-CoV-2.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {2237}, pmid = {36754974}, issn = {2045-2322}, mesh = {Animals ; Chlorocebus aethiops ; Humans ; *SARS-CoV-2 ; Antiviral Agents/pharmacology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Virus Replication ; Vero Cells ; }, abstract = {SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.}, } @article {pmid36754119, year = {2023}, author = {Parhizgar, P and Yazdankhah, N and Rzepka, AM and Chung, KYC and Ali, I and Lai Fat Fur, R and Russell, V and Cheung, AM}, title = {Beyond Acute COVID-19: A Review of Long-term Cardiovascular Outcomes.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {726-740}, pmid = {36754119}, issn = {1916-7075}, support = {VR4-172729//CIHR/Canada ; }, mesh = {Adult ; Humans ; *Myocarditis ; Post-Acute COVID-19 Syndrome ; Acute Disease ; *COVID-19/epidemiology ; Canada/epidemiology ; SARS-CoV-2 ; Disease Progression ; }, abstract = {Statistics Canada estimated that approximately 1.4 million Canadians suffer from long COVID. Although cardiovascular changes during acute SARS-CoV-2 infection are well documented, long-term cardiovascular sequelae are less understood. In this review, we sought to characterize adult cardiovascular outcomes in the months after acute COVID-19 illness. In our search we identified reports of outcomes including cardiac dysautonomia, myocarditis, ischemic injuries, and ventricular dysfunction. Even in patients without overt cardiac outcomes, subclinical changes have been observed. Cardiovascular sequelae after SARS-CoV-2 infection can stem from exacerbation of preexisting conditions, ongoing inflammation, or as a result of damage that occurred during acute infection. For example, myocardial fibrosis has been reported months after hospital admission for COVID-19 illness, and might be a consequence of myocarditis and myocardial injury during acute disease. In turn, myocardial fibrosis can contribute to further outcomes including dysrhythmias and heart failure. Severity of acute infection might be a risk factor for long-term cardiovascular consequences, however, cardiovascular changes have also been reported in young, healthy individuals who had asymptomatic or mild acute disease. Although evolving evidence suggests that previous SARS-CoV-2 infection might be a risk factor for cardiovascular disease, there is heterogeneity in existing evidence, and some studies are marred by measured and unmeasured confounders. Many investigations have also been limited by relatively short follow-up. Future studies should focus on longer term outcomes (beyond 1 year) and identifying the prevalence of outcomes in different populations on the basis of acute and long COVID disease severity.}, } @article {pmid36752386, year = {2023}, author = {Schulder, T and Rudenstine, S and Ettman, CK and Galea, S}, title = {Correlates of long-COVID-19: the role of demographics, chronic illness, and psychiatric diagnosis in an urban sample.}, journal = {Psychology, health & medicine}, volume = {28}, number = {7}, pages = {1831-1843}, doi = {10.1080/13548506.2023.2177684}, pmid = {36752386}, issn = {1465-3966}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/epidemiology ; Chronic Disease ; Demography ; COVID-19 Testing ; }, abstract = {Long-COVID-19 symptoms are an emerging public health issue. This study sought to investigate demographics, chronic illness, and probable psychiatric diagnoses as correlates for long-COVID-19 in an urban adult sample. Self-report Qualtrics surveys were sent to students across City University of New York (CUNY) campuses in New York City in Winter 2021-2022. Binary logistic regressions were used to assess the relation of a range of factors with endorsement of long-COVID-19. Results demonstrated that Latinx participants endorsed higher odds of long-COVID-19, as compared to non-Latinx white participants. Participants who endorsed having a prior chronic illness and those who met the cut-off for probable psychiatric diagnoses all endorsed higher odds of long-COVID-19. Long-COVID-19 may be more likely among specific subpopulations and among persons with other ongoing physical and mental illness.}, } @article {pmid36751643, year = {2023}, author = {Cox, N and Raizada, SR and Barkham, N and Venkatachalam, S and Sheeran, TP and Adizie, T and Sapkota, H and Scott, IC and Muller, S and Bateman, J}, title = {The impact of the COVID-19 pandemic and stringent social distancing measures on health-related quality of life and COVID-19 infection rates in patients with rheumatic disease: a longitudinal analysis through the pandemic.}, journal = {Rheumatology advances in practice}, volume = {7}, number = {1}, pages = {rkad009}, pmid = {36751643}, issn = {2514-1775}, abstract = {OBJECTIVE: The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic and stringent social isolation measures on patients with rheumatic disease (RD) from the beginning of the pandemic (April 2020).

METHODS: In this UK-based single-centre, prospective, observational cohort study, all RD follow-up patients at our centre were invited by SMS text message in April 2020 to participate in the study. Participants completed questionnaires at four time points between April 2020 and December 2021. We collected demographics, clinically extremely vulnerable (CEV) status, short form 12 mental (MCS) and physical health component scores (PCS) for health-related quality of life, vaccination status, COVID-19 infection rates and incidence of long COVID.

RESULTS: We enrolled 1605 patients (female, 69.0%; CEV, 46.5%); 906 of 1605 (56.4%) completed linked responses to our final questionnaire. MCS improved (+0.6, P < 0.05), whereas PCS scores deteriorated (-1.4, P < 0.001) between April 2020 and December 2021. CEV patients had worse mental and physical health scores than non-CEV patients at entry (PCS, 36.7 and 39.3, respectively, P < 0.001; MCS, 40.9 and 43.0, respectively, P < 0.001) and at each time point throughout the study; both mental and physical health outcomes were worse in CEV compared with non-CEV patients (P < 0.001 and P = 0.004, respectively). At study close, 148 of 906 (16.3%) reported COVID infection, with no difference in infection, vaccination or long COVID rates between CEV and non-CEV patients.

CONCLUSIONS: Mental and physical health in RD patients has changed throughout the pandemic; outcomes for both metrics of health were worse in CEV patients, although there were no differences in infection rates between the groups. These data might assist the understanding and planning of future health-care policy and social restrictions in RD patients.

TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT04542031.}, } @article {pmid36750167, year = {2023}, author = {Barnes, HW and Demirdjian, S and Haddock, NL and Kaber, G and Martinez, HA and Nagy, N and Karmouty-Quintana, H and Bollyky, PL}, title = {Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.}, journal = {Matrix biology : journal of the International Society for Matrix Biology}, volume = {116}, number = {}, pages = {49-66}, pmid = {36750167}, issn = {1569-1802}, support = {R01 DC019965/DC/NIDCD NIH HHS/United States ; R01 HL138510/HL/NHLBI NIH HHS/United States ; R01 HL148184/HL/NHLBI NIH HHS/United States ; R01 HL157100/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Hyaluronic Acid ; Inflammation/pathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as the cause of a global pandemic. Infection with SARS-CoV-2 can result in COVID-19 with both acute and chronic disease manifestations that continue to impact many patients long after the resolution of viral replication. There is therefore great interest in understanding the host factors that contribute to COVID-19 pathogenesis. In this review, we address the role of hyaluronan (HA), an extracellular matrix polymer with roles in inflammation and cellular metabolism, in COVID-19 and critically evaluate the hypothesis that HA promotes COVID-19 pathogenesis. We first provide a brief overview of COVID-19 infection. Then we briefly summarize the known roles of HA in airway inflammation and immunity. We then address what is known about HA and the pathogenesis of COVID-19 acute respiratory distress syndrome (COVID-19 ARDS). Next, we examine potential roles for HA in post-acute SARS-CoV-2 infection (PASC), also known as "long COVID" as well as in COVID-associated fibrosis. Finally, we discuss the potential therapeutics that target HA as a means to treat COVID-19, including the repurposed drug hymecromone (4-methylumbelliferone). We conclude that HA is a promising potential therapeutic target for the treatment of COVID-19.}, } @article {pmid36749838, year = {2023}, author = {Furlanis, G and Busan, P and Formaggio, E and Menichelli, A and Lunardelli, A and Ajcevic, M and Pesavento, V and Manganotti, P}, title = {Stuttering-Like Dysfluencies as a Consequence of Long COVID-19.}, journal = {Journal of speech, language, and hearing research : JSLHR}, volume = {66}, number = {2}, pages = {415-430}, doi = {10.1044/2022_JSLHR-22-00381}, pmid = {36749838}, issn = {1558-9102}, mesh = {Humans ; *Stuttering/etiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Speech/physiology ; *Cerebrovascular Disorders ; }, abstract = {PURPOSE: We present two patients who developed neurogenic stuttering after long COVID-19 related to SARS-CoV-2 infection.

METHODS AND RESULTS: Both patients experienced both physical (e.g., fatigue) and cognitive difficulties, which led to impaired function of attention, lexical retrieval, and memory consolidation. Both patients had new-onset stuttering-like speech dysfluencies: Blocks and repetitions were especially evident at the initial part of words and sentences, sometimes accompanied by effortful and associated movements (e.g., facial grimaces and oro-facial movements). Neuropsychological evaluations confirmed the presence of difficulties in cognitive tasks, while neurophysiological evaluations (i.e., electroencephalography) suggested the presence of "slowed" patterns of brain activity. Neurogenic stuttering and cognitive difficulties were evident for 4-5 months after negativization of SARS-CoV-2 nasopharyngeal swab, with gradual improvement and near-to-complete recovery.

CONCLUSIONS: It is now evident that SARS-CoV-2 infection may significantly involve the central nervous system, also resulting in severe and long-term consequences, even if the precise mechanisms are still unknown. In the present report, long COVID-19 resulted in neurogenic stuttering, as the likely consequence of a "slowed" metabolism of (pre)frontal and sensorimotor brain regions (as suggested by the present and previous clinical evidence). As a consequence, the pathophysiological mechanisms related to the appearance of neurogenic stuttering have been hypothesized, which help to better understand the broader and possible neurological consequences of COVID-19.}, } @article {pmid36748919, year = {2023}, author = {Hicks, SD}, title = {Comparison of Symptom Duration Between Children With SARS-CoV-2 and Peers With Other Viral Illnesses During the COVID-19 Pandemic.}, journal = {Clinical pediatrics}, volume = {62}, number = {9}, pages = {1101-1108}, pmid = {36748919}, issn = {1938-2707}, support = {R61 HD105610/HD/NICHD NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; }, mesh = {Child ; Humans ; Child, Preschool ; Adolescent ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Cross-Sectional Studies ; Pain ; }, abstract = {Some children and young people (CYP) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience persistent symptoms, commonly called "long COVID." It remains unclear whether symptoms of SARS-CoV-2 persist longer than those of other respiratory viruses, particularly in young children. This cross-sectional study involved 372 CYP (0-15 years) tested for SARS-CoV-2. Character and duration of symptoms (cough, runny nose, sore throat, rash, diarrhea, vomiting, sore muscles, fatigue, fever, loss of smell) were compared between CYP with a positive test (n = 100) and those with a negative test (n = 272), while controlling for medical/demographic covariates. The average duration of symptoms for CYP with a positive SARS-CoV-2 test (8.5 ± 10 days) did not differ from that of CYP with a negative test (7.2 ± 5 days, P = .71, d = 0.046). A positive SARS-CoV-2 test did not increase the risk (36/372, 10%) of symptoms persisting for ≥3 weeks (odds ratio = 0.96, 95% confidence interval = 0.45-2.0). These results suggest CYP with non-SARS-CoV-2 infections experience a similar duration of symptoms as peers with SARS-CoV-2 infection.}, } @article {pmid36748905, year = {2023}, author = {Dagher, H and Chaftari, AM and Subbiah, IM and Malek, AE and Jiang, Y and Lamie, P and Granwehr, B and John, T and Yepez, E and Borjan, J and Reyes-Gibby, C and Flores, M and Khawaja, F and Pande, M and Ali, N and Rojo, R and Karp, DD and Chaftari, P and Hachem, R and Raad, II}, title = {Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {36748905}, issn = {2050-084X}, support = {P30CA016672/NH/NIH HHS/United States ; }, mesh = {United States ; Female ; Male ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Testing ; SARS-CoV-2 ; *Neoplasms ; Fatigue ; }, abstract = {BACKGROUND: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery.

METHODS: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months.

RESULTS: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons.

CONCLUSIONS: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission.

FUNDING: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.}, } @article {pmid36747962, year = {2023}, author = {Pink, I and Welte, T}, title = {[Not Available].}, journal = {CME (Berlin, Germany)}, volume = {20}, number = {1-2}, pages = {12-17}, pmid = {36747962}, issn = {1614-3744}, } @article {pmid36747883, year = {2023}, author = {Han, E and Gyöngyösi, M}, title = {[Long COVID-A New Challenge in Medicine: Focus on Pregnancy and Breastfeeding].}, journal = {Journal fur gynakologische Endokrinologie (Osterreichische Ausg.)}, volume = {33}, number = {1}, pages = {7-12}, pmid = {36747883}, issn = {1997-6690}, abstract = {Long COVID (coronavirus disease) has been described as a new multi-organ disease, which appears to be more prevalent in women than in men. Pregnant and breastfeeding women are a special subgroup of patients to consider with long COVID, as only scarce data have been collected to date. Menstrual changes are commonly observed during or after COVID-19; some studies also attribute slight changes of cycle length to previous inoculation against the virus. Pregnant women who have a symptomatic infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are at a higher risk for adverse outcomes and pregnancy-associated complications. Moreover, more and robust data are required to evaluate vertical transmission. COVID vaccines are the most effective tool against the pandemic, as they prevent infection, but also appear to be able to ease long COVID symptoms. Vaccines have been proven safe and effective in both pregnant and breastfeeding women. This article aims to present current data on long COVID in pregnant and breastfeeding women and elucidate risk factors and possible treatment options.}, } @article {pmid36745901, year = {2023}, author = {Tillman, TS and Chen, Q and Bondarenko, V and Coleman, JA and Xu, Y and Tang, P}, title = {SARS-CoV-2 Spike Protein Downregulates Cell Surface α7nAChR through a Helical Motif in the Spike Neck.}, journal = {ACS chemical neuroscience}, volume = {14}, number = {4}, pages = {689-698}, pmid = {36745901}, issn = {1948-7193}, support = {R01 DA046939/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *alpha7 Nicotinic Acetylcholine Receptor/genetics ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Mammals ; }, abstract = {A deficiency of the functional α7 nicotinic acetylcholine receptor (α7nAChR) impairs neuronal and immune systems. The SARS-CoV-2 spike protein (S12) facilitates virus cell entry during COVID-19 infection and can also independently disrupt cellular functions. Here, we found that S12 expression significantly downregulated surface expression of α7nAChR in mammalian cells. A helical segment of S12 (L1145-L1152) in the spike neck was identified to be responsible for the downregulation of α7nAChR, as the mutant S12AAA (L1145A-F1148A-L1152A) had minimal effects on surface α7nAChR expression. This S12 segment is homologous to the α7nAChR intracellular helical motif known for binding chaperone proteins RIC3 and Bcl-2 to promote α7nAChR surface expression. Competition from S12 for binding these proteins likely underlies suppression of surface α7nAChR. Considering the critical roles of α7nAChR in cellular functions, these findings provide a new perspective for improving mRNA vaccines and developing treatment options for certain symptoms related to long COVID.}, } @article {pmid36745532, year = {2023}, author = {Doroszko, A and Rola, P and Włodarczak, S and Lesiak, M and Włodarczak, A}, title = {Coronary microvascular dysfunction in the context of long COVID-19: What is the effect of anti-inflammatory treatment? Author's reply.}, journal = {Kardiologia polska}, volume = {81}, number = {3}, pages = {320-321}, doi = {10.33963/KP.a2023.0040}, pmid = {36745532}, issn = {1897-4279}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Myocardial Ischemia ; Anti-Inflammatory Agents ; }, } @article {pmid36744129, year = {2023}, author = {Lai, YJ and Liu, SH and Manachevakul, S and Lee, TA and Kuo, CT and Bello, D}, title = {Biomarkers in long COVID-19: A systematic review.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1085988}, pmid = {36744129}, issn = {2296-858X}, abstract = {PURPOSE: Long COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID.

METHODS: A systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated.

RESULTS: Identified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta.

CONCLUSION: Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.}, } @article {pmid36743679, year = {2022}, author = {Allendes, FJ and Díaz, HS and Ortiz, FC and Marcus, NJ and Quintanilla, R and Inestrosa, NC and Del Rio, R}, title = {Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1095249}, pmid = {36743679}, issn = {2296-858X}, abstract = {A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of "long-COVID," generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.}, } @article {pmid36742994, year = {2022}, author = {Williams, ES and Martins, TB and Shah, KS and Hill, HR and Coiras, M and Spivak, AM and Planelles, V}, title = {Cytokine Deficiencies in Patients with Long-COVID.}, journal = {Journal of clinical & cellular immunology}, volume = {13}, number = {6}, pages = {}, pmid = {36742994}, issn = {2155-9899}, support = {R01 AI143567/AI/NIAID NIH HHS/United States ; }, abstract = {Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of Interferon Gamma (IFNγ) and Interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID. We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.}, } @article {pmid36742339, year = {2023}, author = {Becerra-García, JA and Sánchez-Gutiérrez, T}, title = {[Long-COVID psychological symptoms in child and adolescent population: a standardized proposal for its exploration].}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {41}, number = {6}, pages = {384-385}, pmid = {36742339}, issn = {1578-1852}, } @article {pmid36740547, year = {2023}, author = {Miller, MJ and Feldstein, LR and Holbrook, J and Plumb, ID and Accorsi, EK and Zhang, QC and Cheng, Q and Ko, JY and Wanga, V and Konkle, S and Dimitrov, LV and Bertolli, J and Saydah, S}, title = {Post-COVID conditions and healthcare utilization among adults with and without disabilities-2021 Porter Novelli FallStyles survey.}, journal = {Disability and health journal}, volume = {16}, number = {2}, pages = {101436}, pmid = {36740547}, issn = {1876-7583}, mesh = {Adult ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Disabled Persons ; Surveys and Questionnaires ; Patient Acceptance of Health Care ; }, abstract = {BACKGROUND: Adults with disabilities are at increased risk for SARS-CoV-2 infection and severe disease; whether adults with disabilities are at an increased risk for ongoing symptoms after acute SARS-CoV-2 infection is unknown.

OBJECTIVES: To estimate the frequency and duration of long-term symptoms (>4 weeks) and health care utilization among adults with and without disabilities who self-report positive or negative SARS-CoV-2 test results.

METHODS: Data from a nationwide survey of 4510 U.S. adults administered from September 24, 2021-October 7, 2021, were analyzed for 3251 (79%) participants who self-reported disability status, symptom(s), and SARS-CoV-2 test results (a positive test or only negative tests). Multivariable models were used to estimate the odds of having ≥1 COVID-19-like symptom(s) lasting >4 weeks by test result and disability status, weighted and adjusted for socio-demographics.

RESULTS: Respondents who tested positive for SARS-CoV-2 had higher odds of reporting ≥1 long-term symptom (with disability: aOR = 4.50 [95% CI: 2.37, 8.54] and without disability: aOR = 9.88 [95% CI: 7.13, 13.71]) compared to respondents testing negative. Among respondents who tested positive, those with disabilities were not significantly more likely to experience long-term symptoms compared to respondents without disabilities (aOR = 1.65 [95% CI: 0.78, 3.50]). Health care utilization for reported symptoms was higher among respondents with disabilities who tested positive (40%) than among respondents without disabilities who tested positive (18%).

CONCLUSIONS: Ongoing symptoms among adults with and without disabilities who also test positive for SARS-CoV-2 are common; however, the frequency of health care utilization for ongoing symptoms is two-fold among adults with disabilities.}, } @article {pmid36739132, year = {2023}, author = {Tan, H and Liu, J and Zeng, F}, title = {China needs a scientific long COVID recovery-support platform.}, journal = {Lancet (London, England)}, volume = {401}, number = {10374}, pages = {344-345}, pmid = {36739132}, issn = {1474-547X}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; China/epidemiology ; }, } @article {pmid36739119, year = {2023}, author = {Mungmunpuntipantip, R and Wiwanitkit, V}, title = {Long COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Correspondence.}, journal = {Reumatologia clinica}, volume = {19}, number = {2}, pages = {119}, doi = {10.1016/j.reumae.2022.07.001}, pmid = {36739119}, issn = {2173-5743}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36738380, year = {2023}, author = {Beukenhorst, AL and Koch, CM and Hadjichrysanthou, C and Alter, G and de Wolf, F and Anderson, RM and Goudsmit, J}, title = {SARS-CoV-2 elicits non-sterilizing immunity and evades vaccine-induced immunity: implications for future vaccination strategies.}, journal = {European journal of epidemiology}, volume = {38}, number = {3}, pages = {237-242}, pmid = {36738380}, issn = {1573-7284}, mesh = {Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control ; Vaccination ; *Vaccines ; }, abstract = {Neither vaccination nor natural infection result in long-lasting protection against SARS-COV-2 infection and transmission, but both reduce the risk of severe COVID-19. To generate insights into optimal vaccination strategies for prevention of severe COVID-19 in the population, we extended a Susceptible-Exposed-Infectious-Removed (SEIR) mathematical model to compare the impact of vaccines that are highly protective against severe COVID-19 but not against infection and transmission, with those that block SARS-CoV-2 infection. Our analysis shows that vaccination strategies focusing on the prevention of severe COVID-19 are more effective than those focusing on creating of herd immunity. Key uncertainties that would affect the choice of vaccination strategies are: (1) the duration of protection against severe disease, (2) the protection against severe disease from variants that escape vaccine-induced immunity, (3) the incidence of long-COVID and level of protection provided by the vaccine, and (4) the rate of serious adverse events following vaccination, stratified by demographic variables.}, } @article {pmid36736577, year = {2023}, author = {Banko, A and Miljanovic, D and Cirkovic, A}, title = {Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {130}, number = {}, pages = {108-125}, pmid = {36736577}, issn = {1878-3511}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Herpesvirus 4, Human ; Cytomegalovirus/genetics ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Herpesviridae Infections/epidemiology ; *Herpesviridae/genetics ; Simplexvirus ; *Herpesvirus 6, Human/genetics ; }, abstract = {OBJECTIVES: Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue.

DESIGN AND METHODS: This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022.

RESULTS: The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls.

CONCLUSIONS: Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.}, } @article {pmid36736574, year = {2023}, author = {Seery, V and Raiden, S and Penedo, JMG and Borda, M and Herrera, L and Uranga, M and Marcó Del Pont, M and Chirino, C and Erramuspe, C and Alvarez, LS and Lenoir, M and Morales, LD and Davenport, C and Huespe Auchter, S and Monsalvo, L and Sastoque, L and Gavazzi, M and Russo, C and Sananez, I and Pando, MLÁ and Laufer, N and Muiños, R and Ferrero, F and Geffner, J and Arruvito, L}, title = {Persistent symptoms after COVID-19 in children and adolescents from Argentina.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {129}, number = {}, pages = {49-56}, pmid = {36736574}, issn = {1878-3511}, mesh = {Adult ; Humans ; Adolescent ; Child ; Argentina/epidemiology ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cough/epidemiology/etiology ; }, abstract = {OBJECTIVES: Although long COVID-19 is widely recognized in adults, less information is available about this condition in children, especially in developing countries. Here, we studied the long-term symptoms of SARS-CoV-2 infection beyond 3 months and the associated risk factors in a pediatric population.

METHODS: This observational study included 639 Argentinian children and adolescents with previously confirmed COVID-19 from June 2020-June 2021 and 577 children without previous COVID-19. Parents completed a survey about symptoms that their child had for >3 months after the diagnosis of SARS-CoV-2 infection.

RESULTS: At least one persistent symptom was observed more frequently in children with previous COVID-19 than in the non-COVID-19 group (34% vs 13%, P <0.0001). SARS-CoV-2 infection increased the risk of headache, dizziness, loss of taste, dyspnea, cough, fatigue, muscle pain, and loss of weight by three- to seven-fold. The loss of smell was only reported in infected children. After controlling for the other variables, older age, symptomatic COVID-19, and comorbidities were independent predictors of long-term symptoms.

CONCLUSIONS: One-third of children experienced persistent symptoms after COVID-19. Older age, symptomatic infection, and comorbidities were shown to be risk factors for long COVID-19. Pediatric long COVID-19 is a new condition that requires further investigation.}, } @article {pmid36736191, year = {2023}, author = {Horn, M and Wathelet, M and Amad, A and Martignène, N and Lathiere, T and Khelfaoui, K and Rousselle, M and El Qaoubii, O and Vuotto, F and Faure, K and Creupelandt, C and Vaiva, G and Fovet, T and D'Hondt, F}, title = {Persistent physical symptoms after COVID-19 infection and the risk of Somatic Symptom Disorder.}, journal = {Journal of psychosomatic research}, volume = {166}, number = {}, pages = {111172}, pmid = {36736191}, issn = {1879-1360}, mesh = {Humans ; Female ; Somatoform Disorders/diagnosis/epidemiology/etiology ; *Medically Unexplained Symptoms ; Retrospective Studies ; *COVID-19 ; Communicable Disease Control ; }, abstract = {OBJECTIVE: Evidence shows that many patients with COVID-19 present persistent symptoms after the acute infection. Some patients may be at a high risk of developing Somatic Symptom Disorder (SSD), in which persistent symptoms are accompanied by excessive and disproportionate health-related thoughts, feelings and behaviors regarding these symptoms. This study assessed the frequency of persistent physical symptoms and SSD and their associated factors in patients with confirmed COVID-19.

METHODS: We conducted a longitudinal retrospective study after the first two French lockdowns at the Lille University Hospital (France), including all patients with confirmed COVID-19. Persistent physical symptoms and excessive preoccupations for these symptoms were measured 8 to 10 months after the onset of COVID-19. The combination of the Patient Health Questionnaire-15 and the Somatic Symptom Disorder-B Criteria Scale was used to identify the individuals likely to present with SSD. Two linear regression models were performed to identify sociodemographic and medical risk factors of SSD.

RESULTS: Among the 377 patients with a laboratory-confirmed diagnosis, 220 (58.4%) completed the questionnaires. Sixty-five percent of the 220 included patients required hospitalization, 53.6% presented at least one persistent physical symptom and 10.4% were considered to present SSD. Female sex, older age, infection during the second wave and having probable PTSD were significantly associated with the severity of SSD and SSD was associated with a significantly higher healthcare use.

CONCLUSIONS: The identification of SSD should encourage clinicians to move beyond the artificial somatic/psychiatric dualism and contribute to a better alliance based on multi-disciplinary care.}, } @article {pmid36736066, year = {2023}, author = {Vásconez-González, J and Fernandez-Naranjo, R and Izquierdo-Condoy, JS and Delgado-Moreira, K and Cordovez, S and Tello-De-la-Torre, A and Paz, C and Castillo, D and Izquierdo-Condoy, N and Carrington, SJ and Ortiz-Prado, E}, title = {Comparative analysis of long-term self-reported COVID-19 symptoms among pregnant women.}, journal = {Journal of infection and public health}, volume = {16}, number = {3}, pages = {430-440}, pmid = {36736066}, issn = {1876-035X}, mesh = {Pregnancy ; Female ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; *Pregnancy Complications, Infectious/epidemiology/diagnosis ; Self Report ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; }, abstract = {BACKGROUND: The negative effects of COVID-19 infections during pregnancy have been amply described, however, the persistent sequels of this infection have not been explored so far.

OBJECTIVE: The aim of this study was to describe persisting symptoms after COVID-19 infection in pregnant and non-pregnant women in Ecuador.

METHODS: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 457 surveys were included in this study. We compared risk factor variables and long-term persisting symptoms of pregnant and non-pregnant women in Ecuador.

RESULTS: Overall, 247 (54.1 %) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by non-pregnant women (94.0 %). The most common Long-COVID symptoms in pregnant women were fatigue (10.6 %), hair loss (9.6 %), and difficulty concentrating (6.2 %). We found that pregnant women who smoked had a higher risk of suffering fatigue.

CONCLUSIONS: The most frequent Long-COVID symptoms in pregnant women were fatigue, hair loss, and difficulty concentrating. Apparently, the patterns of presentation of long-term sequelae of SARS-CoV-2 infection in pregnant women do not differ significantly from reports available from studies in the general population.}, } @article {pmid36735950, year = {2022}, author = {Mayo, NL and Ellenbogen, RL and Mendoza, MD and Russell, HA}, title = {The family physician's role in long COVID management.}, journal = {The Journal of family practice}, volume = {71}, number = {10}, pages = {426-431}, doi = {10.12788/jfp.0517}, pmid = {36735950}, issn = {1533-7294}, mesh = {Humans ; *Physicians, Family ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Counseling ; Referral and Consultation ; Physician's Role ; }, abstract = {A paucity of both data and therapeutics presents obstacles to care and makes your role in symptom management, psychological support, and referral-all described here-essential.}, } @article {pmid36735948, year = {2022}, author = {Barry, HC}, title = {A reason for hope in the face of long COVID.}, journal = {The Journal of family practice}, volume = {71}, number = {10}, pages = {421-422}, doi = {10.12788/jfp.0526}, pmid = {36735948}, issn = {1533-7294}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36735149, year = {2023}, author = {Bocci, T and Bertini, A and Campiglio, L and Botta, S and Libelli, G and Guidetti, M and Priori, A}, title = {Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {44}, number = {4}, pages = {1147-1153}, pmid = {36735149}, issn = {1590-3478}, support = {Bando COVID-19//Fondazione Romeo ed Enrica Invernizzi/ ; }, mesh = {Humans ; Adult ; Middle Aged ; *Motor Neurons/physiology ; Myalgia ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; Muscle, Skeletal ; Electromyography ; }, abstract = {INTRODUCTION: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

MATERIALS AND METHODS: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers.

RESULTS: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%).

CONCLUSION: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.}, } @article {pmid36734068, year = {2023}, author = {Guo, Y and Guo, Y and Zhang, Y and Li, F and Yu, J and Zhang, Y and Shen, Z and Mao, R and Zhu, H and Zhang, J}, title = {Factors affecting prolonged SARS-CoV-2 infection and development and validation of predictive nomograms.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28550}, doi = {10.1002/jmv.28550}, pmid = {36734068}, issn = {1096-9071}, mesh = {Humans ; Aged ; *COVID-19 ; Nomograms ; SARS-CoV-2 ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has received much attention since it is associated with mortality and is hypothesized as the cause of long COVID-19 and the emergence of a new variant of concerns. However, a prediction model for the accurate prediction of prolonged infection is still lacking. A total of 2938 confirmed patients with COVID-19 diagnosed by positive reverse transcriptase-polymerase chain reaction tests were recruited retrospectively. This study cohort was divided into a training set (70% of study patients; n = 2058) and a validation set (30% of study patients; n = 880). Univariate and multivariate logistic regression analyses were utilized to identify predictors for prolonged infection. Model 1 included only preadmission variables, whereas Model 2 also included after-admission variables. Nomograms based on variables of Model 1 and Model 2 were built for clinical use. The efficiency of nomograms was evaluated by using the area under the curve, calibration curves, and concordance indexes (C-index). Independent predictors of prolonged infection included in Model 1 were: age ≥75 years, chronic kidney disease, chronic lung disease, partially or fully vaccinated, and booster. Additional independent predictors in Model 2 were: treated with nirmatrelvir/ritonavir more than 5 days after diagnosis and glucocorticoid. The inclusion of after-admission variables in the model slightly improved the discriminatory power (C-index in the training cohort: 0.721 for Model 1 and 0.737 for Model 2; in the validation cohort: 0.699 for Model 1 and 0.719 for Model 2). In our study, we developed and validated predictive models based on readily available variables of preadmission and after-admission for predicting prolonged SARS-CoV-2 infection of patients with COVID-19.}, } @article {pmid36733935, year = {2022}, author = {Karampitsakos, T and Sotiropoulou, V and Katsaras, M and Tsiri, P and Georgakopoulou, VE and Papanikolaou, IC and Bibaki, E and Tomos, I and Lambiri, I and Papaioannou, O and Zarkadi, E and Antonakis, E and Pandi, A and Malakounidou, E and Sampsonas, F and Makrodimitri, S and Chrysikos, S and Hillas, G and Dimakou, K and Tzanakis, N and Sipsas, NV and Antoniou, K and Tzouvelekis, A}, title = {Post-COVID-19 interstitial lung disease: Insights from a machine learning radiographic model.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1083264}, pmid = {36733935}, issn = {2296-858X}, abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 seem to be an emerging global crisis. Machine learning radiographic models have great potential for meticulous evaluation of post-COVID-19 interstitial lung disease (ILD).

METHODS: In this multicenter, retrospective study, we included consecutive patients that had been evaluated 3 months following severe acute respiratory syndrome coronavirus 2 infection between 01/02/2021 and 12/5/2022. High-resolution computed tomography was evaluated through Imbio Lung Texture Analysis 2.1.

RESULTS: Two hundred thirty-two (n = 232) patients were analyzed. FVC% predicted was ≥80, between 60 and 79 and <60 in 74.2% (n = 172), 21.1% (n = 49), and 4.7% (n = 11) of the cohort, respectively. DLCO% predicted was ≥80, between 60 and 79 and <60 in 69.4% (n = 161), 15.5% (n = 36), and 15.1% (n = 35), respectively. Extent of ground glass opacities was ≥30% in 4.3% of patients (n = 10), between 5 and 29% in 48.7% of patients (n = 113) and <5% in 47.0% of patients (n = 109). The extent of reticulation was ≥30%, 5-29% and <5% in 1.3% (n = 3), 24.1% (n = 56), and 74.6% (n = 173) of the cohort, respectively. Patients (n = 13, 5.6%) with fibrotic lung disease and persistent functional impairment at the 6-month follow-up received antifibrotics and presented with an absolute change of +10.3 (p = 0.01) and +14.6 (p = 0.01) in FVC% predicted at 3 and 6 months after the initiation of antifibrotic.

CONCLUSION: Post-COVID-19-ILD represents an emerging entity. A substantial minority of patients presents with fibrotic lung disease and might experience benefit from antifibrotic initiation at the time point that fibrotic-like changes are "immature." Machine learning radiographic models could be of major significance for accurate radiographic evaluation and subsequently for the guidance of therapeutic approaches.}, } @article {pmid36731604, year = {2023}, author = {Crosier, R and Kafil, TS and Paterson, DI}, title = {Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {779-792}, pmid = {36731604}, issn = {1916-7075}, support = {//CIHR/Canada ; }, mesh = {Humans ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; Heart ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; RNA, Messenger ; }, abstract = {After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.}, } @article {pmid36731065, year = {2023}, author = {Kamp, JC and Werlein, C and Plucinski, EKJ and Neubert, L and Welte, T and Lee, PD and Tafforeau, P and Walsh, C and Kuehnel, MP and Schuppan, D and Hoeper, MM and Jonigk, DD and Ackermann, M}, title = {Novel Insight into Pulmonary Fibrosis and Long COVID.}, journal = {American journal of respiratory and critical care medicine}, volume = {207}, number = {8}, pages = {1105-1107}, pmid = {36731065}, issn = {1535-4970}, support = {MR/R025673/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Pulmonary Fibrosis/etiology ; *COVID-19 ; }, } @article {pmid36731064, year = {2023}, author = {Hatabu, H and Kaye, KM and Christiani, DC}, title = {Reply to Kamp et al.: Novel Insight into Pulmonary Fibrosis and Long Covid.}, journal = {American journal of respiratory and critical care medicine}, volume = {207}, number = {8}, pages = {1108}, pmid = {36731064}, issn = {1535-4970}, support = {R01 HL130974/GF/NIH HHS/United States ; R01 HL111024/GF/NIH HHS/United States ; 5U01CA209414/GF/NIH HHS/United States ; DE025208/GF/NIH HHS/United States ; R01 AI165382/AI/NIAID NIH HHS/United States ; R01 HL135142/GF/NIH HHS/United States ; R01 DE025208/DE/NIDCR NIH HHS/United States ; R01 CA203636/GF/NIH HHS/United States ; R01 AI150575/AI/NIAID NIH HHS/United States ; AI165382/GF/NIH HHS/United States ; AI150575/GF/NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Idiopathic Pulmonary Fibrosis ; }, } @article {pmid36730755, year = {2023}, author = {Messinger-Rapport, B and Grubb, B}, title = {Patient-Centered Paradigm for Managing Autonomic Long COVID Symptoms During Sports and Exercise.}, journal = {Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine}, volume = {33}, number = {2}, pages = {e14-e15}, doi = {10.1097/JSM.0000000000001093}, pmid = {36730755}, issn = {1536-3724}, mesh = {Female ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Primary Dysautonomias/diagnosis ; Tachycardia ; Patient-Centered Care ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/therapy ; }, abstract = {This report highlights a new, patient-centered paradigm for managing post-COVID-19 dysautonomia symptoms during sports and exercise. The patient was a healthcare worker exposed before vaccination. She experienced postural orthostatic tachycardia plus exertional tachycardia, with postexertional fatigue, beginning a few weeks after testing positive for COVID-19. Stress test, echo, and an extensive dysautonomia evaluation were negative. Recommended nonpharmacological and pharmacological interventions were poorly tolerated. Prescription of a novel regimen of "basal-dose" ivabradine, plus very low-dose metoprolol according to an exertional "sliding scale" managed symptoms to an acceptable level for work and recreation.}, } @article {pmid36729627, year = {2023}, author = {Moscucci, F and Gallina, S and Bucciarelli, V and Aimo, A and Pelà, G and Cadeddu-Dessalvi, C and Nodari, S and Maffei, S and Meloni, A and Deidda, M and Mercuro, G and Pedrinelli, R and Penco, M and Sciomer, S and Mattioli, AV}, title = {Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.}, journal = {Journal of cardiovascular medicine (Hagerstown, Md.)}, volume = {24}, number = {Suppl 1}, pages = {e15-e23}, pmid = {36729627}, issn = {1558-2035}, mesh = {Female ; Humans ; Male ; *COVID-19/complications ; *Cardiovascular Diseases/diagnosis/epidemiology/complications ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System/physiology ; *Cardiology ; }, abstract = {The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.}, } @article {pmid36729302, year = {2023}, author = {O'Sullivan, O and Holdsworth, DA and Ladlow, P and Barker-Davies, RM and Chamley, R and Houston, A and May, S and Dewson, D and Mills, D and Pierce, K and Mitchell, J and Xie, C and Sellon, E and Naylor, J and Mulae, J and Cranley, M and Talbot, NP and Rider, OJ and Nicol, ED and Bennett, AN}, title = {Cardiopulmonary, Functional, Cognitive and Mental Health Outcomes Post-COVID-19, Across the Range of Severity of Acute Illness, in a Physically Active, Working-Age Population.}, journal = {Sports medicine - open}, volume = {9}, number = {1}, pages = {7}, pmid = {36729302}, issn = {2199-1170}, abstract = {BACKGROUND: The COVID-19 pandemic has led to significant morbidity and mortality, with the former impacting and limiting individuals requiring high physical fitness, including sportspeople and emergency services.

METHODS: Observational cohort study of 4 groups: hospitalised, community illness with on-going symptoms (community-symptomatic), community illness now recovered (community-recovered) and comparison. A total of 113 participants (aged 39 ± 9, 86% male) were recruited: hospitalised (n = 35), community-symptomatic (n = 34), community-recovered (n = 18) and comparison (n = 26), approximately five months following acute illness. Participant outcome measures included cardiopulmonary imaging, submaximal and maximal exercise testing, pulmonary function, cognitive assessment, blood tests and questionnaires on mental health and function.

RESULTS: Hospitalised and community-symptomatic groups were older (43 ± 9 and 37 ± 10, P = 0.003), with a higher body mass index (31 ± 4 and 29 ± 4, P < 0.001), and had worse mental health (anxiety, depression and post-traumatic stress), fatigue and quality of life scores. Hospitalised and community-symptomatic participants performed less well on sub-maximal and maximal exercise testing. Hospitalised individuals had impaired ventilatory efficiency (higher VE/V̇CO2 slope, 29.6 ± 5.1, P < 0.001), achieved less work at anaerobic threshold (70 ± 15, P < 0.001) and peak (231 ± 35, P < 0.001), and had a reduced forced vital capacity (4.7 ± 0.9, P = 0.004). Clinically significant abnormal cardiopulmonary imaging findings were present in 6% of hospitalised participants. Community-recovered individuals had no significant differences in outcomes to the comparison group.

CONCLUSION: Symptomatically recovered individuals who suffered mild-moderate acute COVID-19 do not differ from an age-, sex- and job-role-matched comparison population five months post-illness. Individuals who were hospitalised or continue to suffer symptoms may require a specific comprehensive assessment prior to return to full physical activity.}, } @article {pmid36728728, year = {2024}, author = {Krug, E and Geckeler, KC and Frishman, WH}, title = {Cardiovascular Manifestations of Long COVID: A Review.}, journal = {Cardiology in review}, volume = {32}, number = {5}, pages = {402-407}, doi = {10.1097/CRD.0000000000000520}, pmid = {36728728}, issn = {1538-4683}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Cardiovascular Diseases/etiology/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; }, abstract = {The acute phase of severe acute respiratory syndrome coronavirus 2 [coronavirus disease (COVID)] infection has many well-documented cardiovascular manifestations, however, the long-term sequelae are less understood. In this focused review, we explore the risk factors, character, and rates of cardiovascular events in patients with Long COVID, which is defined as symptoms occurring more than 4 weeks following initial infection. Research has identified increased rates of cerebrovascular disease, dysrhythmias, ischemic and inflammatory heart disease, cardiopulmonary symptoms, and thrombotic events among those with Long COVID, though the risk rates and potential mechanisms behind each cardiovascular event vary. Finally, we discuss the current gaps in the literature as well as how COVID compares to other viral infections when it comes to causing long-term cardiovascular sequelae.}, } @article {pmid36728643, year = {2023}, author = {Baptista de Lima, J and Salazar, L and Fernandes, A and Teixeira, C and Marques, L and Afonso, C}, title = {Long COVID in Children and Adolescents: A Retrospective Study in a Pediatric Cohort.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {4}, pages = {e109-e111}, pmid = {36728643}, issn = {1532-0987}, mesh = {Humans ; Adolescent ; Child ; Retrospective Studies ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Risk Factors ; }, abstract = {Studies on long coronavirus disease (COVID) in children are scarce. We aimed to describe persistent symptoms and identify risk factors for its development. In our study population, 17.6% presented with long COVID, with respiratory symptoms more frequent in the first weeks and neuropsychiatric symptoms over time. Chronic conditions and obesity were risk factors, and adolescents were at a greater risk for long COVID.}, } @article {pmid36727514, year = {2023}, author = {Gerlach, J and Baig, AM and Fabrowski, M and Viduto, V}, title = {The immune paradox of SARS-CoV-2: Lymphocytopenia and autoimmunity evoking features in COVID-19 and possible treatment modalities.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2423}, doi = {10.1002/rmv.2423}, pmid = {36727514}, issn = {1099-1654}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Autoimmunity ; *Lymphopenia ; }, abstract = {SARS-CoV-2 causes multiorgan damage to vital organs and tissue that are known to be due to a combination of tissue tropisms and cytokine-mediated damage that it can incite in COVID-19. The effects of SARS-Co-2 on the lymphocytes and therefore on the immune response have attracted attention recently in COVID-19 to understand its effects in causing a chronic state of ongoing infection with Long-COVID. The associated lymphopaenia and autoimmune disease state, which is an apparent paradox, needs to be researched to dissect possible mechanisms underlying this state. This paper attempts to unravel the aforesaid immune paradox effects of SARS-CoV-2 on the lymphocytes and discusses appropriate treatment modalities with antiviral drugs and nutraceuticals which could prove virucidal in SARS-CoV-2 seeding monocytes and lymphocytes in patients with COVID-19 and Long-COVID. Importantly it proposes a new in vitro treatment modality of immune regulating cells that can help patients fight the lymphopaenia associated with COVID-19 and Long-COVID.}, } @article {pmid36726198, year = {2023}, author = {Müller, T and Riederer, P and Kuhn, W}, title = {Aminoadamantanes: from treatment of Parkinson's and Alzheimer's disease to symptom amelioration of long COVID-19 syndrome?.}, journal = {Expert review of clinical pharmacology}, volume = {16}, number = {2}, pages = {101-107}, doi = {10.1080/17512433.2023.2176301}, pmid = {36726198}, issn = {1751-2441}, mesh = {Humans ; Memantine/pharmacology/therapeutic use ; Post-Acute COVID-19 Syndrome ; *Alzheimer Disease/drug therapy ; *Parkinson Disease/drug therapy ; *COVID-19 ; Amantadine/pharmacology/therapeutic use ; }, abstract = {INTRODUCTION: The aminoadamantanes amantadine and memantine are well known. They mainly act as N-methyl-D-aspartate antagonists.

AREAS COVERED: The antiviral drug amantadine moderately ameliorates impaired motor behavior in patients with Parkinson's disease. Memantine provides beneficial effects on memory function in patients with advanced Alzheimer's disease already treated with acetylcholine esterase inhibitors. Both compounds counteract impaired monoamine neurotransmission with associated symptoms, such as depression. They improve vigilance, lack of attention and concentration, fatigue syndromes according to clinical findings in patients with chronic neurodegenerative processes. Their extrasynaptic N-methyl-D-Aspartate receptor blockade weakens a prolonged influx of Ca[2+] ions as the main responsible components of neuronal excitotoxicity. This causes neuronal dying and associated functional deficits.

EXPERT OPINION: We suggest aminoadamantanes as future therapies for amelioration of short- and long-term consequences of a COVID 19 infection. Particularly the extended-release amantadine formulations will be suitable. They showed better clinical efficacy compared with the conventional available compounds. Amantadine may particularly be suitable for amelioration of fatigue or chronic exhaustion, memantine for improvement of cognitive deficits. Clinical research in patients, who are affected by the short- and long-term consequences of a COVID 19 infection, is warranted to confirm these still hypothetical putative beneficial effects of aminoadamantanes.}, } @article {pmid36726167, year = {2023}, author = {Potter, C and Leggat, F and Lowe, R and Pallmann, P and Riaz, M and Barlow, C and Edwards, A and Siriwardena, AN and Sevdalis, N and Sewell, B and McRae, J and Fish, J and de Sousa de Abreu, MI and Jones, F and Busse, M}, title = {Effectiveness and cost-effectiveness of a personalised self-management intervention for living with long COVID: protocol for the LISTEN randomised controlled trial.}, journal = {Trials}, volume = {24}, number = {1}, pages = {75}, pmid = {36726167}, issn = {1745-6215}, support = {COV-LT2-0009//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Cost-Benefit Analysis ; *Self-Management ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Individuals living with long COVID experience multiple, interacting and fluctuating symptoms which can have a dramatic impact on daily living. The aim of the Long Covid Personalised Self-managemenT support EvaluatioN (LISTEN) trial is to evaluate effects of the LISTEN co-designed self-management support intervention for non-hospitalised people living with long COVID on participation in routine activities, social participation, emotional well-being, quality of life, fatigue, and self-efficacy. Cost-effectiveness will also be evaluated, and a detailed process evaluation carried out to understand how LISTEN is implemented.

METHODS: The study is a pragmatic randomised effectiveness and cost-effectiveness trial in which a total of 558 non-hospitalised people with long COVID will be randomised to either the LISTEN intervention or usual care. Recruitment strategies have been developed with input from the LISTEN Patient and Public Involvement and Engagement (PPIE) advisory group and a social enterprise, Diversity and Ability, to ensure inclusivity. Eligible participants can self-refer into the trial via a website or be referred by long COVID services. All participants complete a range of self-reported outcome measures, online, at baseline, 6 weeks, and 3 months post randomisation (the trial primary end point). Those randomised to the LISTEN intervention are offered up to six one-to-one sessions with LISTEN-trained intervention practitioners and given a co-designed digital resource and paper-based book. A detailed process evaluation will be conducted alongside the trial to inform implementation approaches should the LISTEN intervention be found effective and cost-effective.

DISCUSSION: The LISTEN trial is evaluating a co-designed, personalised self-management support intervention (the LISTEN intervention) for non-hospitalised people living with long COVID. The design has incorporated extensive strategies to minimise participant burden and maximise access. Whilst the duration of follow-up is limited, all participants are approached to consent for long-term follow-up (subject to additional funding being secured).

TRIAL REGISTRATION: LISTEN ISRCTN36407216. Registered on 27/01/2022.}, } @article {pmid36725436, year = {2023}, author = {Parodi, JB and Indavere, A and Bobadilla Jacob, P and Toledo, GC and Micali, RG and Waisman, G and Masson, W and Epstein, ED and Huerin, MS}, title = {Impact of COVID-19 vaccination in post-COVID cardiac complications.}, journal = {Vaccine}, volume = {41}, number = {8}, pages = {1524-1528}, pmid = {36725436}, issn = {1873-2518}, mesh = {Humans ; *COVID-19/complications/prevention & control ; *COVID-19 Vaccines/adverse effects ; *Heart Diseases/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; Vaccination/adverse effects ; }, abstract = {BACKGROUND: After the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms.

METHODS: All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis.

RESULTS: From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17-0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40-0.69, p<0.001).

CONCLUSION: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.}, } @article {pmid36720183, year = {2023}, author = {Kudoh, R and Komiya, K and Shinohara, A and Kageyama, T and Hiramatsu, K and Kadota, JI}, title = {Marital status and post-COVID-19 conditions.}, journal = {Respiratory investigation}, volume = {61}, number = {2}, pages = {181-185}, pmid = {36720183}, issn = {2212-5353}, mesh = {Humans ; *COVID-19 ; Depression/diagnosis/psychology ; Marital Status ; Surveys and Questionnaires ; Anxiety/diagnosis ; }, abstract = {Although studies have investigated the factors associated with psychological post-COVID-19 symptoms, the impact of marital status on symptom development has not been fully determined. This study conducts a questionnaire survey to investigate the association between marital status and the proportion of patients with post-COVID-19 symptoms in 749 cases as valid responses. Depressive state and memory impairment were more frequently seen in the no-spouse group when each symptom was compared according to marital status. Particularly in individuals in the 40s who had minor COVID-19 illness, this trend was noted. Single patients with mild COVID-19 illness may need proactive psychological support.}, } @article {pmid36720058, year = {2023}, author = {Riepl, M}, title = {Compounding for the Treatment of COVID-19 and Long COVID, Part 1: Terminology, Mutations, and Variants.}, journal = {International journal of pharmaceutical compounding}, volume = {27}, number = {1}, pages = {12-21}, pmid = {36720058}, issn = {1092-4221}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; Mutation ; }, abstract = {COVID-19 (coronavirus disease 2019), which is caused by the positive-stranded ribonucleic acid virus SARS-CoV-2 (acute respiratory syndrome coronavirus 2), is an extremely contagious airborne illness of pandemic proportions. In the modern era, few diseases other than COVID-19 have produced such severe, prolific, and protean short-term adverse effects and long-term sequelae. In addition, few other pandemics have exhibited a trajectory of morbidity and mortality so affected by social, economic, and political factors as well as individual personal perceptions and beliefs. Vaccines for the prevention of SARS-CoV-2 infection and treatments for COVID-19 mitigate associated morbidity and mortality, but an increasing array of variants presents challenges to therapeutic effectiveness. As a result, afflicted patients often require customized treatments that address the severity of their infection, the manifestations of disease they exhibit, and their individual pharmacogenomic profile. In such cases, a compounded preparation may offer needed support for recovery. This article, which is the first in a series on compounding for COVID-19 and long COVID (i.e., the long- term sequelae of SARS-CoV-2 infection), provides information about pertinent viral terminology and a brief overview of SARS-CoV-2 mutations and variants of note. Two formulations for customized compounds that may prove effective in treating the acute and/or long-term effects of COVID-19 when commercial therapies have failed are also provided.}, } @article {pmid36719540, year = {2023}, author = {Musheyev, B and Boparai, MS and Kimura, R and Janowicz, R and Pamlanye, S and Hou, W and Duong, TQ}, title = {Longitudinal medical subspecialty follow-up of critically and non-critically ill hospitalized COVID-19 survivors up to 24 months after discharge.}, journal = {Internal and emergency medicine}, volume = {18}, number = {2}, pages = {477-486}, pmid = {36719540}, issn = {1970-9366}, mesh = {Humans ; *COVID-19/epidemiology/therapy ; Patient Discharge ; SARS-CoV-2 ; Retrospective Studies ; Follow-Up Studies ; Aftercare ; Survivors ; Intensive Care Units ; }, abstract = {Medical specialty usage of COVID-19 survivors after hospital discharge is poorly understood. This study investigated medical specialty usage at 1-12 and 13-24 months post-hospital discharge in critically ill and non-critically ill COVID-19 survivors. This retrospective study followed ICU (N = 89) and non-ICU (N = 205) COVID-19 survivors who returned for follow-up within the Stony Brook Health System post-hospital discharge. Follow-up data including survival, hospital readmission, ongoing symptoms, medical specialty care use, and ICU status were examined 1-12 and 13-24 months after COVID-19 discharge. "New" (not previously seen) medical specialty usage was also identified. Essentially all (98%) patients survived. Hospital readmission was 34%, but functional status scores at discharge were not associated with hospital readmission. Many patients reported ongoing [neuromuscular (50%) respiratory (39%), chronic fatigue (35%), cardiovascular (30%), gastrointestinal (28%), neurocognitive (22%), genitourinary (22%), and mood-related (13%)] symptoms at least once 1-24 months after discharge. Common specialty follow-ups included cardiology (25%), vascular medicine (17%), urology (17%), neurology (16%), and pulmonology (14%), with some associated with pre-existing comorbidities and with COVID-19. Common new specialty visits were vascular medicine (11%), pulmonology (11%), and neurology (9%). ICU patients had more symptoms and follow-ups compared to the non-ICU patients. This study reported high incidence of persistent symptoms and medical specialty care needs in hospitalized COVID-19 survivors 1-24 months post-discharge. Some specialty care needs were COVID-19 related or exacerbated by COVID-19 disease while others were associated with pre-existing medical conditions. Longer follow-up studies of COVID-19 survivor medical care needs are necessary.}, } @article {pmid36719069, year = {2023}, author = {Teodoro, T and Chen, J and Gelauff, J and Edwards, MJ}, title = {Functional neurological disorder in people with long COVID: A systematic review.}, journal = {European journal of neurology}, volume = {30}, number = {5}, pages = {1505-1514}, doi = {10.1111/ene.15721}, pmid = {36719069}, issn = {1468-1331}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Conversion Disorder ; Anosmia ; Fatigue/etiology ; }, abstract = {BACKGROUND AND PURPOSE: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). It was hypothesized that a proportion of people with long COVID might be experiencing functional symptoms.

METHODS: A systematic review of studies containing original data on long COVID was performed. The frequency and characteristics of neurological symptoms were reviewed, looking for positive evidence suggesting an underlying functional disorder and the hypothesized causes of long COVID.

RESULTS: In all, 102 studies were included in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms and ageusia/anosmia. Overall, no evidence was found that any authors had systematically looked for positive features of FND. An exception was three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterized to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesized that some people with long COVID might have a functional disorder, and another eight studies a chronic-fatigue-syndrome-like response.

DISCUSSION: Neurological symptoms are prevalent in long COVID, but poorly characterized. The similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses are striking. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long COVID might in part correspond to a functional disorder remains untested.}, } @article {pmid36718484, year = {2023}, author = {Diekman, S and Chung, T}, title = {Post-acute sequelae of SARS-CoV-2 syndrome presenting as postural orthostatic tachycardia syndrome.}, journal = {Clinical and experimental emergency medicine}, volume = {10}, number = {1}, pages = {18-25}, pmid = {36718484}, issn = {2383-4625}, abstract = {The novel SARS-CoV-2 emerged in 2019, and the global COVID-19 pandemic continues into 2022. It has been known that a subset of patients develops chronic, debilitating symptoms after otherwise complete recovery from acute infection of COVID-19. Multiple terms have been used to describe this constellation of symptoms, including long COVID, long-haul COVID, and postacute sequelae of SARS-CoV-2 syndrome (PASC). PASC is broadly defined as a wide range of new, returning, or ongoing symptoms at least four weeks after infection. Those patients are often seen in emergency departments after acute COVID-19 infection, but their symptoms are not adequately managed because the underlying pathophysiology of PASC is not well understood. Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. POTS is one of the most common forms of autonomic dysfunction and defined by a sustained orthostatic tachycardia during active standing or head-up tilt test in the absence of orthostatic hypotension or other cardiopulmonary diseases. Because POTS is a treatable condition, it is important to recognize POTS among PASC patients. Herein, we reviewed the current literature on POTS and dysautonomia in PASC in order to better understand the overlap and distinction between these pathologies.}, } @article {pmid36718418, year = {2022}, author = {Barrett, P and Das, S and Magistretti, G and Pugacheva, E and Wingender, P}, title = {Long COVID? Prospects for economic scarring from the pandemic.}, journal = {Contemporary economic policy}, volume = {}, number = {}, pages = {}, pmid = {36718418}, issn = {1074-3529}, abstract = {This paper examines the potential persistent effects (scarring) of the COVID-19 pandemic on the economy and the channels through which they may occur. Our findings from a broad set of historical recessions confirm that recessions are associated with persistent output losses and that the greatest scarring has occurred following financial crises. The amount of scarring following pandemic and epidemic recessions in the sample is in between that of typical recessions and financial crises. Results on the channels show that the productivity channel is important, as all types of recessions have been followed by persistent losses to total factor productivity.}, } @article {pmid36718227, year = {2023}, author = {Varma-Doyle, A and Villemarette-Pittman, NR and Lelorier, P and England, J}, title = {Demonstrating new-onset or worsened sudomotor function post-COVID-19 on comparative analysis of autonomic function pre-and post-SARS-CoV-2 infection.}, journal = {eNeurologicalSci}, volume = {30}, number = {}, pages = {100445}, pmid = {36718227}, issn = {2405-6502}, abstract = {BACKGROUND: Autonomic dysfunction including sudomotor abnormalities have been reported in association with SARS-CoV-2 infection.

OBJECTIVE: There are no previous studies that have compared autonomic function objectively in patients pre- and post- SARS-CoV-2 infection.We aimed to identify if SARS-CoV-2 virus is triggering and/or worsening dysautonomia by comparing autonomic function tests in a group of patients pre-and post-SARS-CoV-2 infection.

DESIGN/METHODS: Six participants were enrolled and divided into two groups. The first group of 4 participants reported worsened autonomic symptoms post-SARS-CoV-2 infection. These individuals had their first autonomic test prior to COVID-19 pandemic outbreak (July 2019-December 2019). Autonomic function testing was repeated in these participants, 6 months to 1-year post-SARS-CoV-2 infection (June 2021).The second group of 2 participants reported new-onset autonomic symptoms post-COVID-19 infection and were also tested within 6 months post-SARS-CoV-2 infection.All participants had mild COVID-19 infection per WHO criteria. They had no evidence of large fiber neuropathy as demonstrated by normal neurophysiological studies (EMG/NCS). They were all screened for known causes of autonomic dysfunction and without risk factors of hypertension/hyperlipidemia, thyroid dysfunction, diabetes/prediabetes, vitamin deficiencies, history of HIV, hepatitis, or syphilis, prior radiation or chemical exposure or evidence of monoclonal gammopathy, or autoimmune condition.

RESULTS: Participants were female (age: 21-37y) and all endorsed orthostatic intolerance (6/6). Gastrointestinal symptoms (⅚), new-onset paresthesias, (3/6), and sexual dysfunction (2/6) were reported. Parasympathetic autonomic function remained stable 6-months to 1-year post-COVID-19 infection and no parasympathetic dysfunction was demonstrated in participants with new-onset dysautonomia symptoms. Postural orthostatic tachycardia was noted in half of the patients, being observed in one patient pre- SARS-CoV-2 infection and persisting post-SARS-CoV-2 infection; while new-onset postural tachycardia was observed in 1/3rd of patients. Sympathetic cholinergic (sudomotor) dysfunction was demonstrated in ALL participants. Worsened, or new-onset, sudomotor dysfunction was demonstrated in those with mild or normal sudomotor function on pre-COVID-19 autonomic testing.

CONCLUSIONS: Sympathetic adrenergic and cholinergic dysautonomia probably account for some of the symptoms of Long COVID-19. Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. However, the findings in our study are preliminary, and studies with larger sample size are needed to confirm these observations.}, } @article {pmid36717724, year = {2023}, author = {Cron, RQ}, title = {Immunologic prediction of long COVID.}, journal = {Nature immunology}, volume = {24}, number = {2}, pages = {207-208}, pmid = {36717724}, issn = {1529-2916}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Hospitalization ; }, } @article {pmid36717723, year = {2023}, author = {Ruffieux, H and Hanson, AL and Lodge, S and Lawler, NG and Whiley, L and Gray, N and Nolan, TH and Bergamaschi, L and Mescia, F and Turner, L and de Sa, A and Pelly, VS and , and Kotagiri, P and Kingston, N and Bradley, JR and Holmes, E and Wist, J and Nicholson, JK and Lyons, PA and Smith, KGC and Richardson, S and Bantug, GR and Hess, C}, title = {A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.}, journal = {Nature immunology}, volume = {24}, number = {2}, pages = {349-358}, pmid = {36717723}, issn = {1529-2916}, support = {219506/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MR/L019027/MRC_/Medical Research Council/United Kingdom ; MR/L019027/1/MRC_/Medical Research Council/United Kingdom ; MR/W018861/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 200871/Z/16/ Z/WT_/Wellcome Trust/United Kingdom ; 200871/WT_/Wellcome Trust/United Kingdom ; 200871/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Kynurenine ; Patient-Centered Care ; }, abstract = {The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.}, } @article {pmid36714125, year = {2022}, author = {Schaefer, LV and Bittmann, FN}, title = {Case report: Individualized pulsed electromagnetic field therapy in a Long COVID patient using the Adaptive Force as biomarker.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {879971}, pmid = {36714125}, issn = {2296-858X}, abstract = {The increasing prevalence of Long COVID is an imminent public health disaster, and established approaches have not provided adequate diagnostics or treatments. Recently, anesthetic blockade of the stellate ganglion was reported to improve Long COVID symptoms in a small case series, purportedly by "rebooting" the autonomic nervous system. Here, we present a novel diagnostic approach based on the Adaptive Force (AF), and report sustained positive outcome for one severely affected Long COVID patient using individualized pulsed electromagnetic field (PEMF) at the area C7/T1. AF reflects the capacity of the neuromuscular system to adapt adequately to external forces in an isometric holding manner. In case, maximal isometric AF (AFisomax) is exceeded, the muscle merges into eccentric muscle action. Thereby, the force usually increases further until maximal AF (AFmax) is reached. In case adaptation is optimal, AFisomax is ~99-100% of AFmax. This holding capacity (AFisomax) was found to be vulnerable to disruption by unpleasant stimulus and, hence, was regarded as functional parameter. AF was assessed by an objectified manual muscle test using a handheld device. Prior to treatment, AFisomax was considerably lower than AFmax for hip flexors (62 N = ~28% AFmax) and elbow flexors (71 N = ~44% AFmax); i.e., maximal holding capacity was significantly reduced, indicating dysfunctional motor control. We tested PEMF at C7/T1, identified a frequency that improved neuromuscular function, and applied it for ~15 min. Immediately post-treatment, AFisomax increased to ~210 N (~100% AFmax) at hip and 184 N (~100% AFmax) at elbow. Subjective Long COVID symptoms resolved the following day. At 4 weeks post-treatment, maximal holding capacity was still on a similarly high level as for immediately post-treatment (~100% AFmax) and patient was symptom-free. At 6 months the patient's Long COVID symptoms have not returned. This case report suggests (1) AF could be a promising diagnostic for post-infectious illness, (2) AF can be used to test effective treatments for post-infectious illness, and (3) individualized PEMF may resolve post-infectious symptoms.}, } @article {pmid36711624, year = {2023}, author = {Guo, B and Zhao, C and He, MZ and Senter, C and Zhou, Z and Peng, J and Li, S and Fitzpatrick, AL and Lindström, S and Stebbins, RC and Noppert, GA and Li, C}, title = {Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36711624}, support = {R00 AG062749/AG/NIA NIH HHS/United States ; R01 AG070953/AG/NIA NIH HHS/United States ; R01 AG075719/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: There is growing body of literature on the long-term cardiac symptoms following COVID-19. We conducted a systematic review and meta-analysis to synthesize and evaluate related evidence to inform clinical management and future studies.

METHODS: We searched two preprint and seven peer-reviewed article databases from January 1, 2020 to January 8, 2022 for studies investigating cardiac symptoms that persisted for at least 4 weeks among individuals who survived COVID-19. A customized Newcastle-Ottawa scale was used to evaluate the quality of included studies. Random-effects meta-analyses were performed to estimate the proportion of symptoms with 95% confidence intervals (CI), and stratified analyses were conducted to quantify the proportion of symptoms by study characteristics and quality.

RESULTS: A total of 101 studies describing 49 unique long-term cardiac symptoms met the inclusion criteria. Based on quality assessment, only 15.8% of the studies (n=16) were of high quality, and most studies scored poorly on sampling representativeness. The two most examined symptoms were chest pain and arrhythmia. Meta-analysis showed that the proportion of chest pain was 10.1% (95% CI: 6.4-15.5) and arrhythmia was 9.8% (95% CI: 5.4-17.2). Stratified analyses showed that studies with low-quality score, small sample size, unsystematic sampling method, and cross-sectional design were most likely to report high proportions of symptoms. For example, the proportion of chest pain was 21.3% (95% CI: 10.5-38.5), 9.3% (95% CI: 6.0-14.0), and 4.0% (95% CI: 1.3-12.0) in studies with low, medium, and high-quality scores, respectively. Similar patterns were observed for other cardiac symptoms including hypertension, cardiac abnormalities, myocardial injury, thromboembolism, stroke, heart failure, coronary disease, and myocarditis.

DISCUSSION: There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology.}, } @article {pmid36711488, year = {2023}, author = {Socia, D and Larie, D and Feuerwerker, S and An, G and Cockrell, C}, title = {Prediction of Long COVID Based on Severity of Initial COVID-19 Infection: Differences in predictive feature sets between hospitalized versus non-hospitalized index infections.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36711488}, abstract = {Long COVID is recognized as a significant consequence of SARS-COV2 infection. While the pathogenesis of Long COVID is still a subject of extensive investigation, there is considerable potential benefit in being able to predict which patients will develop Long COVID. We hypothesize that there would be distinct differences in the prediction of Long COVID based on the severity of the index infection, and use whether the index infection required hospitalization or not as a proxy for developing predictive models. We divide a large population of COVID patients drawn from the United States National Institutes of Health (NIH) National COVID Cohort Collaborative (N3C) Data Enclave Repository into two cohorts based on the severity of their initial COVID-19 illness and correspondingly trained two machine learning models: the Long COVID after Severe Disease Model (LCaSDM) and the Long COVID after Mild Disease Model (LCaMDM). The resulting models performed well on internal validation/testing, with a F1 score of 0.94 for the LCaSDM and 0.82 for the LCaMDM. There were distinct differences in the top 10 features used by each model, possibly reflecting the differences in type and amount of pathophysiological data between the hospitalized and non-hospitalized patients and/or reflecting different pathophysiological trajectories in the development of Long COVID. Of particular interest was the importance of Plant Hardiness Zone in the feature set for the LCaMDM, which may point to a role of climate and/or sunlight in the progression to Long COVID. Future work will involve a more detailed investigation of the potential role of climate and sunlight, as well as refinement of the predictive models as Long COVID becomes increasingly parsed into distinct clinical phenotypes.}, } @article {pmid36711478, year = {2023}, author = {Antar, AAR and Yu, T and Demko, ZO and Hu, C and Tornheim, JA and Blair, PW and Thomas, DL and Manabe, YC and , }, title = {Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.01.18.23284742}, pmid = {36711478}, support = {K23 AI135102/AI/NIAID NIH HHS/United States ; }, abstract = {The incidence of long COVID is substantial, even in people who did not require hospitalization for acute COVID-19. The pathobiological mechanisms of long COVID and the role of early viral kinetics in its development are largely unknown. Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long- COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset. Brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). This work indicates that at least two long COVID symptoms - brain fog and muscle pain - at 90+ days from acute COVID-19 onset are specifically associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract.}, } @article {pmid36710996, year = {2023}, author = {Kaufmann, J and Gould, O and Lloyd, V}, title = {Seeking Care for Long COVID: A Narrative Analysis of Canadian Experiences.}, journal = {Journal of patient experience}, volume = {10}, number = {}, pages = {23743735231151770}, pmid = {36710996}, issn = {2374-3735}, abstract = {The goal of this study was to explore the experiences of individuals seeking care for long COVID-19 in the Canadian healthcare system. Recorded virtual interviews were carried out with 8 participants and narrative analysis was used to examine the stories produced and identify the central narratives that defined participants' experiences. Care-seeking experiences were characterized by (1) often debilitating multi-system symptoms for which little information about prognosis was available and no effective treatments were provided, (2) compounded by the frustration of trying to convince family, friends, and health care practitioners of the legitimacy of their illness, (3) access to medical care was severely limited by the global pandemic and associated higher thresholds for care, (4) like others suffering from complex, multi-system conditions, people with long COVID are often struggling with a health-care system ill-suited for dealing with long-term and possibly chronic conditions. To make system-level improvements to better serve those with chronic conditions, it is critical that we understand the care-seeking experiences of chronic illness patients, including the unique experiences of those with long COVID.}, } @article {pmid36710628, year = {2023}, author = {Sobczak, E and Swafford, EP and Samano, D and Bass, D and Ghamasaee, P and Kottapally, M and Merenda, A and O'Phelan, K and Romano, JG and Sacco, RL and Rundek, T and Alkhachroum, A}, title = {Posttraumatic Stress Symptoms Among COVID-19 Survivors After Hospitalization.}, journal = {The Journal of neuropsychiatry and clinical neurosciences}, volume = {35}, number = {3}, pages = {256-261}, doi = {10.1176/appi.neuropsych.20220126}, pmid = {36710628}, issn = {1545-7222}, mesh = {Humans ; Female ; Middle Aged ; Aged ; Male ; *Stress Disorders, Post-Traumatic/epidemiology/etiology/diagnosis ; Aftercare ; Patient Discharge ; *COVID-19/epidemiology/complications ; Survivors/psychology ; }, abstract = {OBJECTIVE: Limited data are available on posttraumatic stress symptoms (PTSS) among COVID-19 survivors. This study aimed to contribute to this knowledge base.

METHODS: PTSS among COVID-19 survivors who had been hospitalized were investigated. Patients were identified as COVID-19 positive at hospital admission. COVID-19 survivors were surveyed with the Posttraumatic Stress Disorder Checklist (PCL-5) between March and October 2020 at 5- and 12-month postdischarge follow-up points.

RESULTS: Of 411 patients, 331 (81%) survived to hospital discharge. Of these survivors, 83 (25%) completed the PCL-5 at the 5-month follow-up. Of those patients, 12 (14%) screened positive for PTSS. At the 12-month follow-up, four of eight patients remained PTSS positive. Mean age of follow-up participants was 62±15 years; 47% were women, 65% were White, and 63% were Hispanic. PTSS-positive patients were predominantly non-White (67% vs. 30%, p=0.02), and although the differences were not statistically significant, these patients tended to be younger (56 vs. 63 years, p=0.08) and have shorter intensive care unit stays (2.0 vs. 12.5 days, p=0.06). PTSS-positive and PTSS-negative groups did not differ significantly in prehospitalization neurological diagnoses (11% vs. 8%), psychiatric diagnoses (17% vs. 21%), and intensive care admission status (25% vs. 25%). More patients in the PTSS-positive group had returned to the emergency department (50% vs. 14%, p<0.01) and reported fatigue at follow-up (100% vs. 42%, p<0.001). In the multivariate logistic regression model, non-White race (OR=11, 95% CI=2-91) and returning to the emergency department (OR=19, 95% CI=3-252) were associated with PTSS-positive status.

CONCLUSION: PTSS were twice as common among hospitalized COVID-19 survivors than among those in the general population.}, } @article {pmid36709621, year = {2023}, author = {Hitch, D and Deféin, E and Lloyd, M and Rasmussen, B and Haines, K and Garnys, E and , }, title = {Beyond the case numbers: Social determinants and contextual factors in patient narratives of recovery from COVID-19.}, journal = {Australian and New Zealand journal of public health}, volume = {47}, number = {1}, pages = {100002}, pmid = {36709621}, issn = {1753-6405}, mesh = {Adult ; Humans ; Australia/epidemiology ; *COVID-19 ; COVID-19 Testing ; Pandemics ; *Social Determinants of Health ; Post-Acute COVID-19 Syndrome ; New Zealand ; }, abstract = {OBJECTIVE: This study aimed to describe and contextualise COVID-19 recovery from the perspective of patient-lived experience, to inform the evolving public health response to the pandemic.

METHODS: Narrative interviews were completed with 37 adult Australians between six and 10 months following their COVID-19 diagnosis. Verbatim transcripts were analysed thematically and trustworthiness was supported by multiple strategies to ensure rigour.

RESULTS: Three themes were identified: 1) trajectories of recovery, 2) back to 'some sort of normal' and 3) the importance of work. Resumed participation in activities of daily life, the influence of social determinants of health and the impact of contextual factors were prominent features in the recovery narratives.

CONCLUSIONS: The COVID-19 pandemic presents both challenges and opportunities for public health systems to formulate appropriate responses and make improvements. Behind the case numbers, patient narratives described the uncertainty, diversity and multiple pathways to recovery that need to inform public health policy.

Looking beyond the case numbers reveals a complex landscape characterised by uncertainty, diversity and multiple pathways to recovery. The pandemic presents challenges and opportunities for public health in Australia and New Zealand, lived experience expertise is crucial to the formulation of an effective response.}, } @article {pmid36709220, year = {2023}, author = {Baker, SR and Halliday, G and Ząbczyk, M and Alkarithi, G and Macrae, FL and Undas, A and Hunt, BJ and Ariëns, RAS}, title = {Plasma from patients with pulmonary embolism show aggregates that reduce after anticoagulation.}, journal = {Communications medicine}, volume = {3}, number = {1}, pages = {12}, pmid = {36709220}, issn = {2730-664X}, abstract = {BACKGROUND: Microclots, a term also used for amyloid fibrin(ogen) particles and henceforth named aggregates, have recently been reported in the plasma of patients with COVID-19 and long COVID. These aggregates have been implicated in the thrombotic complications of these diseases.

METHODS: Plasma samples from 35 patients with acute pulmonary embolism were collected and analysed by laser scanning confocal microscopy and scanning electron microscopy before and after clotting.

RESULTS: Here we confirm the presence of aggregates and show that they also occur in the plasma of patients with pulmonary embolism, both before and after clotting. Aggregates vary in size and consist of fibrin and platelets. We show that treatment with low-molecular weight heparin reduces aggregates in the samples of patients with pulmonary embolism. Double centrifugation of plasma does not eliminate the aggregates.

CONCLUSIONS: These data corroborate the existence of microclots or aggregates in diseases associated with venous thromboembolism. Important questions are raised regarding their pathophysiological relevance and further studies are warranted to investigate whether they represent cause or consequence of clinical thrombosis.}, } @article {pmid36709083, year = {2023}, author = {Mantovani, A and Rescigno, M and Forni, G and Tognon, F and Putoto, G and Ictho, J and Lochoro, P}, title = {COVID-19 vaccines and a perspective on Africa.}, journal = {Trends in immunology}, volume = {44}, number = {3}, pages = {172-187}, pmid = {36709083}, issn = {1471-4981}, mesh = {Humans ; COVID-19 Vaccines ; *COVID-19 ; Pandemics/prevention & control ; *Vaccines ; Immunity, Innate ; Vaccination ; }, abstract = {Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.}, } @article {pmid36708796, year = {2025}, author = {Haslam, A and Prasad, V}, title = {Comparability of Control and Comparison Groups in Studies Assessing Long COVID.}, journal = {The American journal of medicine}, volume = {138}, number = {1}, pages = {148-152.e3}, pmid = {36708796}, issn = {1555-7162}, mesh = {Humans ; Control Groups ; *COVID-19/epidemiology ; Observational Studies as Topic ; Post-Acute COVID-19 Syndrome ; Randomized Controlled Trials as Topic ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Awareness of long coronavirus disease (COVID) began primarily through media and social media sources, which eventually led to the development of various definitions based on methodologies of varying quality. We sought to characterize comparison groups in long COVID studies and evaluate comparability of the different groups.

METHODS: We searched Embase, Web of Science, and PubMed for original research articles published in high-impact journals. We included studies on human patients with long COVID outcomes, and we abstracted study-related characteristics, as well as long COVID characteristics.

RESULTS: Of the 83 studies, 3 were randomized controlled trials testing interventions for long COVID, and 80 (96.4%) were observational studies. Among the 80 observational studies, 76 (95%) were trying to understand the incidence, prevalence, and risk factors for long COVID, 2 (2.5%) examined prevention strategies, and 2 (2.5%) examined treatment strategies. Among those 80 studies, 45 (56.2%) utilized a control or comparison group and 35 (43.8%) did not. Compared with 95% of observational studies that documented symptoms or assessed risk factors, all randomized studies assessed treatment strategies. We found 48.8% of observational studies did any adjustment for covariates, including demographics or health status. Of those that did adjust for covariates, 15 (38.5%) adjusted for 4 or fewer variables. We found that 26.5% of all studies and 45.8% of studies with a control/comparator group matched participants on at least 1 variable.

CONCLUSION: Long COVID studies in high-impact journals primarily examine symptoms and risk factors of long COVID; often lack an adequate comparison group and often do not control for potential confounders. Our results suggest that standardized definitions for long COVID, which are often based on data from uncontrolled and potentially biased studies, should be reviewed to ensure that they are based on objective data.}, } @article {pmid36708608, year = {2023}, author = {Mullard, JCR and Kawalek, J and Parkin, A and Rayner, C and Mir, G and Sivan, M and Greenhalgh, T}, title = {Towards evidence-based and inclusive models of peer support for long covid: A hermeneutic systematic review.}, journal = {Social science & medicine (1982)}, volume = {320}, number = {}, pages = {115669}, pmid = {36708608}, issn = {1873-5347}, support = {COV-LT2-0016/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hermeneutics ; Delivery of Health Care ; Peer Group ; }, abstract = {Since the first wave of COVID-19 in March 2020 the number of people living with post-COVID syndrome has risen rapidly at global pace, however, questions still remain as to whether there is a hidden cohort of sufferers not accessing mainstream clinics. This group are likely to be constituted by already marginalised people at the sharp end of existing health inequalities and not accessing formal clinics. The challenge of supporting such patients includes the question of how best to organise and facilitate different forms of support. As such, we aim to examine whether peer support is a potential option for hidden or hardly reached populations of long COVID sufferers with a specific focus on the UK, though not exclusively. Through a systematic hermeneutic literature review of peer support in other conditions (57 papers), we evaluate the global potential of peer support for the ongoing needs of people living with long COVID. Through our analysis, we highlight three key peer support perspectives in healthcare reflecting particular theoretical perspectives, goals, and understandings of what is 'good health', we call these: biomedical (disease control/management), relational (intersubjective mutual support) and socio-political (advocacy, campaigning & social context). Additionally, we identify three broad models for delivering peer support: service-led, community-based and social media. Attention to power relations, social and cultural capital, and a co-design approach are key when developing peer support services for disadvantaged and underserved groups. Models from other long-term conditions suggest that peer support for long COVID can and should go beyond biomedical goals and harness the power of relational support and collective advocacy. This may be particularly important when seeking to reduce health inequalities and improve access for a potentially hidden cohort of sufferers.}, } @article {pmid36708022, year = {2023}, author = {Yong, SJ and Halim, A and Halim, M and Liu, S and Aljeldah, M and Al Shammari, BR and Alwarthan, S and Alhajri, M and Alawfi, A and Alshengeti, A and Khamis, F and Alsalman, J and Alshukairi, AN and Abukhamis, NA and Almaghrabi, FS and Almuthree, SA and Alsulaiman, AM and Alshehail, BM and Alfaraj, AH and Alhawaj, SA and Mohapatra, RK and Rabaan, AA}, title = {Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2424}, doi = {10.1002/rmv.2424}, pmid = {36708022}, issn = {1099-1654}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Biomarkers ; SARS-CoV-2 ; C-Reactive Protein ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.}, } @article {pmid36707454, year = {2023}, author = {Elmazny, A and Magdy, R and Hussein, M and Elsebaie, EH and Ali, SH and Abdel Fattah, AM and Hassan, M and Yassin, A and Mahfouz, NA and Elsayed, RM and Fathy, W and Abdel-Hamid, HM and Abdelbadie, M and Soliman, SH}, title = {Neuropsychiatric post-acute sequelae of COVID-19: prevalence, severity, and impact of vaccination.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {273}, number = {6}, pages = {1349-1358}, pmid = {36707454}, issn = {1433-8491}, mesh = {Humans ; Adult ; Middle Aged ; *COVID-19/complications/epidemiology/prevention & control ; COVID-19 Vaccines/adverse effects ; Prevalence ; *Sleep Initiation and Maintenance Disorders ; Disease Progression ; Fatigue/epidemiology/etiology ; }, abstract = {The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415-2.683), 3.86 times (OR 3.86, 95% CI = 2.358-6.329), and 1.67 times (OR 1.67, 95% CI = 1.253-2.216), respectively. Fully vaccinated subjects before COVID-19 infection (n = 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (P value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.}, } @article {pmid36705268, year = {2023}, author = {Gottlieb, M and Wang, RC and Yu, H and Spatz, ES and Montoy, JCC and Rodriguez, RM and Chang, AM and Elmore, JG and Hannikainen, PA and Hill, M and Huebinger, RM and Idris, AH and Lin, Z and Koo, K and McDonald, S and O'Laughlin, KN and Plumb, ID and Santangelo, M and Saydah, S and Willis, M and Wisk, LE and Venkatesh, A and Stephens, KA and Weinstein, RA and , }, title = {Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {11}, pages = {1930-1941}, pmid = {36705268}, issn = {1537-6591}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; /CC/CDC HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; COVID-19 Testing ; Prospective Studies ; Fatigue/epidemiology/etiology ; }, abstract = {BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron).

METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status.

RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants.

CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.}, } @article {pmid36703736, year = {2022}, author = {Jiang, L and An, X and Duan, Y and Lian, F and Jin, D and Zhang, Y and Yang, C and Zhang, Y and Kang, X and Sun, Y}, title = {The pathological mechanism of the COVID-19 convalescence and its treatment with traditional Chinese medicine.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1054312}, pmid = {36703736}, issn = {1663-9812}, abstract = {The severe acute respiratory syndrome coronavirus - 2 (SARS - CoV - 2) was reported to cause the Wuhan outbreak of the corona virus disease 2019(COVID-19). To date, the COVID-19 has infected more than 600 million people gloabally. As a growing number of patients recover from acute infections and are discharged from hospitals, the proportion of patients in the recovery period is gradually increasing. Many of these individuals have been reported to experience multiple symptoms during the convalescence, such as fatigue, dyspnea and pain which are designated as "long-COVID", "post-COVID syndrome" or "recovery sequelae. We searched for recent articles published in PubMed on COVID-19 convalescence and found that the pathogenesis of COVID-19 convalescence is not yet well recognized. It may be associated with incomplete recovery of immune system, parenchymal organ damage (liver or lung), coagulation abnormalities, "second hit" caused by viral infection, and Phenomenon of Cell Senescence-Associated Secretory Phenotype (SASP). Some drugs and psychological factors of patients also play a non-negligible role in it. We also found that the effect of traditional Chinese medicine (TCM) is effective in the treatment of the COVID-19 recovery phase, which can not only relieve the corresponding symptoms, but also improve the indicators and pulmonary fibrosis. Bufei Huoxue Capsule, as the only drug explicitly mentioned for COVID-19 recovery period, can exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19. In addition, in previous studies, traditional Chinese medicine has been confirmed to have the ability to resist cytokine storms, as well as improve coagulation and myocardial damage, which makes it have potential therapeutic advantages in targeting the hyperimmune response, coagulation abnormalities and myocardial damage existing in the recovery period. In conclusion, the clinical symptoms of patients convalescing from COVID-19 are complex, and its pathogenesis has not been elucidated. traditional Chinese medicine, as a traditional treatment, its specific action and mechanism need to be confirmed by more studies, so that it can play a better role.}, } @article {pmid36703253, year = {2023}, author = {Landry, M and Bornstein, S and Nagaraj, N and Sardon, GA and Castel, A and Vyas, A and McDonnell, K and Agneshwar, M and Wilkinson, A and Goldman, L}, title = {Postacute Sequelae of SARS-CoV-2 in University Setting.}, journal = {Emerging infectious diseases}, volume = {29}, number = {3}, pages = {519-527}, pmid = {36703253}, issn = {1080-6059}, mesh = {Humans ; Female ; Male ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Universities ; Mental Health ; }, abstract = {Postacute sequelae of SARS-CoV-2 infection, commonly known as long COVID, is estimated to affect 10% to 80% of COVID-19 survivors. We examined the prevalence and predictors of long COVID from a sample of 1,338 COVID-19 cases among university members in Washington, DC, USA, during July 2021‒March 2022. Cases were followed up after 30 days of the initial positive result with confidential electronic surveys including questions about long COVID. The prevalence of long COVID was 36%. Long COVID was more prevalent among those who had underlying conditions, who were not fully vaccinated, who were female, who were former/current smokers, who experienced acute COVID-19 symptoms, who reported higher symptom counts, who sought medical care, or who received antibody treatment. Understanding long COVID among university members is imperative to support persons who have ongoing symptoms and to strengthen existing services or make referrals to other services, such as mental health, exercise programs, or long-term health studies.}, } @article {pmid36702551, year = {2023}, author = {Lu, JY and Boparai, MS and Shi, C and Henninger, EM and Rangareddy, M and Veeraraghavan, S and Mirhaji, P and Fisher, MC and Duong, TQ}, title = {Long-term outcomes of COVID-19 survivors with hospital AKI: association with time to recovery from AKI.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {38}, number = {10}, pages = {2160-2169}, doi = {10.1093/ndt/gfad020}, pmid = {36702551}, issn = {1460-2385}, mesh = {Humans ; Aftercare ; Patient Discharge ; *COVID-19/complications ; *Acute Kidney Injury/epidemiology/etiology/therapy ; *Renal Insufficiency, Chronic/complications/therapy/epidemiology ; Hospitals ; Risk Factors ; Survivors ; Retrospective Studies ; }, abstract = {BACKGROUND: Although coronavirus disease 2019 (COVID-19) patients who develop in-hospital acute kidney injury (AKI) have worse short-term outcomes, their long-term outcomes have not been fully characterized. We investigated 90-day and 1-year outcomes after hospital AKI grouped by time to recovery from AKI.

METHODS: This study consisted of 3296 COVID-19 patients with hospital AKI stratified by early recovery (<48 hours), delayed recovery (2-7 days) and prolonged recovery (>7-90 days). Demographics, comorbidities and laboratory values were obtained at admission and up to the 1-year follow-up. The incidence of major adverse cardiovascular events (MACE) and major adverse kidney events (MAKE), rehospitalization, recurrent AKI and new-onset chronic kidney disease (CKD) were obtained 90-days after COVID-19 discharge.

RESULTS: The incidence of hospital AKI was 28.6%. Of the COVID-19 patients with AKI, 58.0% experienced early recovery, 14.8% delayed recovery and 27.1% prolonged recovery. Patients with a longer AKI recovery time had a higher prevalence of CKD (P < .05) and were more likely to need invasive mechanical ventilation (P < .001) and to die (P < .001). Many COVID-19 patients developed MAKE, recurrent AKI and new-onset CKD within 90 days, and these incidences were higher in the prolonged recovery group (P < .05). The incidence of MACE peaked 20-40 days postdischarge, whereas MAKE peaked 80-90 days postdischarge. Logistic regression models predicted 90-day MACE and MAKE with 82.4 ± 1.6% and 79.6 ± 2.3% accuracy, respectively.

CONCLUSION: COVID-19 survivors who developed hospital AKI are at high risk for adverse cardiovascular and kidney outcomes, especially those with longer AKI recovery times and those with a history of CKD. These patients may require long-term follow-up for cardiac and kidney complications.}, } @article {pmid36701357, year = {2023}, author = {Cooper, E and Lound, A and Atchison, CJ and Whitaker, M and Eccles, C and Cooke, GS and Elliott, P and Ward, H}, title = {Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280943}, pmid = {36701357}, issn = {1932-6203}, support = {MC_PC_20049/MRC_/Medical Research Council/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; COV-LT-0040/DH_/Department of Health/United Kingdom ; MR/L01341X/1/MRC_/Medical Research Council/United Kingdom ; RE/18/4/34215/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; Female ; Male ; Adult ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Communicable Disease Control ; SARS-CoV-2 ; Qualitative Research ; }, abstract = {BACKGROUND: Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

METHODS: People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

RESULTS: We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

CONCLUSION: This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.}, } @article {pmid36700308, year = {2023}, author = {Liu, ST and Lin, SC and Chang, JP and Yang, KJ and Chu, CS and Yang, CC and Liang, CS and Sun, CF and Wang, SC and Satyanarayanan, SK and Su, KP}, title = {The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS).}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {21}, number = {1}, pages = {10-18}, pmid = {36700308}, issn = {1738-1088}, abstract = {There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.}, } @article {pmid36700201, year = {2022}, author = {Linnhoff, S and Koehler, L and Haghikia, A and Zaehle, T}, title = {The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {935614}, pmid = {36700201}, issn = {1664-3224}, mesh = {Humans ; *Transcranial Direct Current Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/complications/therapy ; Brain/physiology ; Cognition/physiology ; }, abstract = {Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.}, } @article {pmid36699926, year = {2022}, author = {Ahmed, T and Pooja, SD and Nandonik, AJ and Mostafa, S and Kabir, ZN}, title = {Sociodemographic, economic, physical, and mental health status of previously hospitalised patients with COVID-19 symptoms in Bangladesh: Protocol for a mixed-method study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {763812}, pmid = {36699926}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; Bangladesh/epidemiology ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Health Status ; }, abstract = {INTRODUCTION: Not much is known about the long-term consequences of COVID-19, popularly known as long COVID. This is particularly so in terms of patterns and clusters of symptoms over time, sociodemographic and economic characteristics of patients, and related clinical history. This is crucial for resource-constrained health systems such as Bangladesh to address long COVID as a forthcoming challenge. This protocol aims to investigate the consequences of COVID-19 over time for physical and mental health and how these are associated with demographic and socio-economic factors.

METHODS AND ANALYSIS: This mixed-method study collected information on all patients with symptoms of COVID-19 admitted to and discharged after recovery from a COVID-19-dedicated hospital in Bangladesh (N = 942), from April to December 2020. The sources of data were admission records and discharge certificates from the hospital for clinical history, cross-sectional survey on physical and mental health (assessed by DASS21 scale)-related symptoms and socioeconomic changes after recovery, and qualitative in-depth interviews on experiences of COVID-19. Interviews were conducted over the phone. Quantitative analysis was done to estimate the prevalence of physical and mental health consequences of COVID-19 after recovery and the association with socio-economic and demographic information. The qualitative analysis was performed using a thematic analysis approach.

DISCUSSION: It is imperative to understand the post-COVID consequences and related health and non-health aspects to inform evidence-based policymaking, especially for resource-poor contexts such as Bangladesh. Given the dearth of evidence in this regard, the proposed study will contribute to bridging this knowledge gap. It is important to note that this study is one of the few which presents information on post-COVID-19 consequences in the context of low- and middle-income countries and the first in Bangladesh.}, } @article {pmid36698837, year = {2022}, author = {Imamura, M and Uchyiama, SST and Naves, GS and Abicalaf, CARP and Mirisola, AR and Dos Santos, ACA and Battistella, LR and , }, title = {Ultrasonographic findings in long COVID: A cross-sectional study of 312 patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1051389}, pmid = {36698837}, issn = {2296-858X}, abstract = {BACKGROUND: Fatigue and muscle weakness are common complaints in COVID-19 survivors. However, little is still known about the skeletal muscle qualitative and quantitative characteristics after hospitalization due to moderate and severe COVID-19.

OBJECTIVES: To assess rectus femoris and vastus intermedius muscle thickness (MT) and rectus femoris echo intensity (EI) and to establish its association with demographic, clinical, functional, and inflammatory parameters in long COVID patients after hospital discharge.

METHODS: Cross-sectional study with 312 COVID-19 patients (53.53% male; age: 54.59 ± 13.50 years), with a laboratory-confirmed diagnosis of COVID-19. Patients were assessed 3-11 months after hospital discharge. We evaluated MT of the right rectus femoris and vastus intermedius and EI of the right rectus femoris using a portable ultrasound system, 6-13 MHz, broadband linear transducer. We corrected EI using the subcutaneous fat thickness. Ultrasonographic parameters were tested in association with demographic (sex and age); functional (Handgrip strength measurement, Timed Up and Go, 1 min Sit-to-Stand test, EuroQoL-5 Dimensions-5 Levels, World Health Organization Disability Assessment Schedule (WHODAS 2.0), Post-COVID-19 Functional Status, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), Medical Research Council (MRC) sum score, Borg Dyspnea Scale, MRC Dyspnea score, Visual Analogue Scale (VAS), Epworth Sleepiness Scale, Insomnia Severity Index, Functional Independence Measurement (FIM), and Functional Oral Intake Scale); clinical (length of hospital stay, intubation, and presence of comorbidities such as systemic hypertension, diabetes, obesity, chronic obstructive pulmonary disease, asthma), and inflammatory data assessed by the C-reactive protein and D-dimer serum concentrations.

RESULTS: Rectus femoris MT was associated with age, handgrip strength, Epworth Sleepiness Scale, and subcutaneous fat thickness (r[2] = 27.51%; p < 0.0001). Vastus intermedius MT was associated with age, pain intensity, handgrip strength, Epworth Sleepiness scale, FIM, and time since hospital discharge (r[2] = 21.12%; p < 0.0001). Rectus femoris EI was significantly associated with the male sex, TUG, Epworth Sleepiness Scale, and C-Reactive Protein levels (r[2] = 44.39%; p < 0.0001). Mean MT of rectus femoris and vastus intermedius are significantly different (p < 0.001).

CONCLUSION: After hospital discharge, long COVID patients present qualitative and quantitative skeletal muscle characteristics associated with a combination of demographic, clinical, and functional parameters.}, } @article {pmid36698810, year = {2022}, author = {Oliveira, CR and Jason, LA and Unutmaz, D and Bateman, L and Vernon, SD}, title = {Improvement of Long COVID symptoms over one year.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1065620}, pmid = {36698810}, issn = {2296-858X}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; L40 AI120154/AI/NIAID NIH HHS/United States ; U54 NS105539/NS/NINDS NIH HHS/United States ; }, abstract = {IMPORTANCE: Early and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.

METHODS: This prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of >3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.

PARTICIPANTS: Patients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.

RESULTS: At baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.

CONCLUSION AND RELEVANCE: There were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.}, } @article {pmid36698809, year = {2022}, author = {Dissook, S and Umsumarng, S and Mapoung, S and Semmarath, W and Arjsri, P and Srisawad, K and Dejkriengkraikul, P}, title = {Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-COVID.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1072056}, pmid = {36698809}, issn = {2296-858X}, abstract = {OBJECTIVE: The multi-systemic inflammation as a result of COVID-19 can persevere long after the initial symptoms of the illness have subsided. These effects are referred to as Long-COVID. Our research focused on the contribution of the Spike protein S1 subunit of SARS-CoV-2 (Spike S1) on the lung inflammation mediated by NLRP3 inflammasome machinery and the cytokine releases, interleukin 6 (IL-6), IL-1beta, and IL-18, in lung epithelial cells. This study has attempted to identify the naturally- occurring agents that act against inflammation-related long-COVID. The seed meal of Perilla frutescens (P. frutescens), which contains two major dietary polyphenols (rosmarinic acid and luteolin), has been reported to exhibit anti-inflammation activities. Therefore, we have established the ethyl acetate fraction of P. frutescens seed meal (PFEA) and determined its anti-inflammatory effects on Spike S1 exposure in A549 lung cells.

METHODS: PFEA was established using solvent-partitioned extraction. Rosmarinic acid (Ra) and luteolin (Lu) in PFEA were identified using the HPLC technique. The inhibitory effects of PFEA and its active compounds against Spike S1-induced inflammatory response in A549 cells were determined by RT-PCR and ELISA. The mechanistic study of anti-inflammatory properties of PFEA and Lu were determined using western blot technique.

RESULTS: PFEA was found to contain Ra (388.70 ± 11.12 mg/g extract) and Lu (248.82 ± 12.34 mg/g extract) as its major polyphenols. Accordingly, A549 lung cells were pre-treated with PFEA (12.5-100 μg/mL) and its two major compounds (2.5-20 μg/mL) prior to the Spike S1 exposure at 100 ng/mL. PFEA dose-dependently exhibited anti-inflammatory properties upon Spike S1-exposed A549 cells through IL-6, IL-1β, IL-18, and NLRP3 gene suppressions, as well as IL-6, IL-1β, and IL-18 cytokine releases with statistical significance (p < 0.05). Importantly, Lu possesses superior anti-inflammatory properties when compared with Ra (p < 0.01). Mechanistically, PFEA and Lu effectively attenuated a Spike S1-induced inflammatory response through downregulation of the JAK1/STAT3-inflammasome-dependent inflammatory pathway as evidenced by the downregulation of NLRP3, ASC, and cleaved-caspase-1 of the NLRP3 inflammasome components and by modulating the phosphorylation of JAK1 and STAT3 proteins (p < 0.05).

CONCLUSION: The findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.}, } @article {pmid36698111, year = {2023}, author = {Samper-Pardo, M and Oliván-Blázquez, B and Magallón-Botaya, R and Méndez-López, F and Bartolomé-Moreno, C and León-Herrera, S}, title = {The emotional well-being of Long COVID patients in relation to their symptoms, social support and stigmatization in social and health services: a qualitative study.}, journal = {BMC psychiatry}, volume = {23}, number = {1}, pages = {68}, pmid = {36698111}, issn = {1471-244X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life/psychology ; Stereotyping ; Social Support ; Health Services ; }, abstract = {BACKGROUND: Long COVID patients have experienced a decline in their quality of life due to, in part but not wholly, its negative emotional impact. Some of the most prevalent mental health symptoms presented by long COVID patients are anxiety, depression, and sleep disorders. As such, the need has arisen to analyze the personal experiences of these patients to understand how they are managing their daily lives while dealing with the condition. The objective of this study is to increase understanding about the emotional well-being of people diagnosed with long COVID.

METHODS: A qualitative design was created and carried out using 35 patients, with 17 participants being interviewed individually and 18 of them taking part in two focus groups. The participating patients were recruited in November and December 2021 from Primary Health Care (PHC) centers in the city of Zaragoza (Northern Spain) and from the Association of Long COVID Patients in Aragon. The study topics were emotional well-being, social support networks, and experience of discrimination. All an inductive thematic content analyses were performed iteratively using NVivo software.

RESULTS: The Long COVID patients identified low levels of self-perceived well-being due to their persistent symptoms, as well as limitations in their daily lives that had been persistent for many months. Suicidal thoughts were also mentioned by several patients. They referred to anguish and anxiety about the future as well as a fear of reinfection or relapse and returning to work. Many of the participants reported that they have sought the help of a mental health professional. Most participants identified discriminatory situations in health care.

CONCLUSIONS: It is necessary to continue researching the impact that Long COVID has had on mental health, as well as to provide Primary Health Care professionals with evidence that can guide the emotional treatment of these patients.}, } @article {pmid36697009, year = {2023}, author = {Wilmshurst, P and Bewley, S and Murray, P}, title = {Hyperbaric oxygen therapy for the treatment of long COVID.}, journal = {Clinical medicine (London, England)}, volume = {23}, number = {1}, pages = {99-100}, pmid = {36697009}, issn = {1473-4893}, mesh = {Humans ; *Hyperbaric Oxygenation ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Oxygen ; }, } @article {pmid36695924, year = {2023}, author = {Wang, SSY and Xu, C}, title = {Hydroxychloroquine: is there a role in long COVID?.}, journal = {Clinical rheumatology}, volume = {42}, number = {3}, pages = {977-978}, pmid = {36695924}, issn = {1434-9949}, mesh = {Humans ; Hydroxychloroquine/adverse effects ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; *Antimalarials/therapeutic use ; }, } @article {pmid36695893, year = {2023}, author = {Ludwig, B and Olbert, E and Trimmel, K and Seidel, S and Rommer, PS and Müller, C and Struhal, W and Berger, T}, title = {[Myalgic encephalomyelitis/chronic fatigue syndrome: an overview of current evidence].}, journal = {Der Nervenarzt}, volume = {94}, number = {8}, pages = {725-733}, pmid = {36695893}, issn = {1433-0407}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/therapy/epidemiology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Comorbidity ; }, abstract = {Over the past 5 years both media and scientific interest has surged regarding the disorder myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS), not least because of the clinically similar manifestation in long COVID or post-COVID. In this review we discuss the process of clinical diagnosis and randomized controlled therapeutic studies on ME/CFS, and the similarities or differences to long COVID and post-COVID. So far, neither clear pathophysiologically causal nor therapeutic evidence-based results on ME/CFS have been identified in the many years of scientific research. Given the evident psychiatric comorbidity rates in patients with a diagnosis of ME/CFS, a psychosomatic etiology of this syndrome should be considered. Furthermore, a precise and reliable diagnostic classification based on stricter criteria would benefit both pathophysiological and therapeutic research.}, } @article {pmid36695546, year = {2023}, author = {Berg, SK and Birk, NM and Thorsted, AB and Rosenkilde, S and Jensen, LB and Nygaard, U and Bundgaard, H and Thygesen, LC and Ersbøll, AK and Nielsen, SD and Christensen, AV}, title = {Risk of body weight changes among Danish children and adolescents during the COVID-19 pandemic.}, journal = {Pediatric obesity}, volume = {18}, number = {4}, pages = {e13005}, doi = {10.1111/ijpo.13005}, pmid = {36695546}, issn = {2047-6310}, mesh = {Adolescent ; Child ; Humans ; Child, Preschool ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pandemics ; SARS-CoV-2 ; Obesity ; Weight Gain ; Weight Loss ; Denmark ; }, abstract = {BACKGROUND: Knowledge of COVID-19 and the pandemic's effects on Danish children's body weight is limited.

OBJECTIVE: Objectives were to investigate (I) risk of weight changes among Danish children with and without SARS-CoV-2, (II) associations between weight changes, psychological symptoms, and long COVID symptoms, and (III) weight distribution pre- and post-pandemic.

METHODS: A national survey was administered to all Danish children aged 0-18 years, with prior COVID-19 (cases) and matched references including questions on weight, weight changes during the pandemic and long COVID-related symptoms. Descriptive statistics and logistic regression were used. Weight distribution was compared with a pre-pandemic database.

RESULTS: In all, 17 627 cases and 54 656 references were included. The 4-18-year-old cases had lower odds of unintended weight gain. The 2-3-year-old cases had higher odds and the 15-18-year-old cases lower odds of weight loss compared to references. Regardless of COVID-19 status, any reported long COVID-related symptom was associated with a change in body weight. No sign of increasing obesity rates was found among Danish children post-pandemic.

CONCLUSION: COVID-19 was associated with higher odds of weight loss in 2-3-year-olds and lower odds of unintended weight gain in 4-18-year-olds. Any long COVID-related symptom was associated with higher odds of weight changes regardless of COVID-19 status.}, } @article {pmid36695401, year = {2023}, author = {Constantinescu-Bercu, A and Kessler, A and de Groot, R and Dragunaite, B and Heightman, M and Hillman, T and Price, LC and Brennan, E and Sivera, R and Vanhoorelbeke, K and Singh, D and Scully, M}, title = {Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {21}, number = {1}, pages = {94-100}, pmid = {36695401}, issn = {1538-7836}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Thrombin ; *Antifibrinolytic Agents ; Quality of Life ; ADAM Proteins/metabolism ; *COVID-19/complications ; von Willebrand Factor/metabolism ; *Thrombosis/etiology ; Collagen ; ADAMTS13 Protein ; }, abstract = {BACKGROUND: Post-COVID syndrome (PCS) affects millions of people worldwide, causing a multitude of symptoms and impairing quality of life months or even years after acute COVID-19. A prothrombotic state has been suggested; however, underlying mechanisms remain to be elucidated.

OBJECTIVES: To investigate thrombogenicity in PCS using a microfluidic assay, linking microthrombi, thrombin generation, and the von Willebrand factor (VWF):a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13 (ADAMTS13) axis.

METHODS: Citrated blood was perfused through microfluidic channels coated with collagen or an antibody against the VWF A3 domain, and thrombogenicity was monitored in real time. Thrombin generation assays were performed and α(2)-antiplasmin, VWF, and ADAMTS13 activity levels were also measured.

RESULTS: We investigated thrombogenicity in a cohort of 21 patients with PCS with a median time following symptoms onset of 23 months using a dynamic microfluidic assay. Our data show a significant increase in platelet binding on both collagen and anti-VWF A3 in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). Thrombi forming on collagen presented different geometries in patients with PCS vs controls, with significantly increased thrombi area mainly attributable to thrombi length in the patient group. Thrombi length positively correlated with VWF(Ag):ADAMTS13 ratio and thrombin generation assay results, which were increased in 55.5% of patients. α(2)-Antiplasmin levels were normal in 89.5% of patients.

CONCLUSION: Together, these data present a dynamic assay to investigate the prothrombotic state in PCS, which may help unravel the mechanisms involved and/or establish new therapeutic strategies for this condition.}, } @article {pmid36694110, year = {2023}, author = {Squillace, N and Cogliandro, V and Rossi, E and Bellelli, G and Pozzi, M and Luppi, F and Lettino, M and Strepparava, MG and Ferrarese, C and Pollastri, E and Ricci, E and Bonfanti, P and , }, title = {A multidisciplinary approach to screen the post-COVID-19 conditions.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {54}, pmid = {36694110}, issn = {1471-2334}, mesh = {Adolescent ; Adult ; Humans ; Male ; *COVID-19 ; Hospitalization ; Intensive Care Units ; *Peripheral Nervous System Diseases ; SARS-CoV-2 ; Female ; }, abstract = {BACKGROUND: Post-COronaVIrus Disease 2019 (COVID-19) conditions (PCC) include multiple symptoms afflicting different organs and systems. To evaluate the frequency and type of them, we described our multidisciplinary approach with preliminary results of the first enrolled patients.

METHODS: We included patients aged ≥ 18 years with hospital admission for confirmed SARS-CoV-2 infection. Symptoms were grouped in five macro groups hereafter referred to as "Symptoms Category" (SC): respiratory SC (dyspnoea or cough), neurological SC (peripheral neuropathies, headache, impaired mobility, behavioural disorders), psychological SC (sleep disorders, mood disorders), muscular SC (arthromyalgia, asthenia), other SC (fever, alopecia, diarrhoea, weight loss, smell and taste alterations, sexual dysfunctions). SC were evaluated at discharge and at follow-up. Association between patients' characteristics and presence of SC at follow up was estimated by a logistic multivariable regression model.

RESULTS: From June 2020 to July 2021, we followed up 361 patients: 128 (35.5%) who were previously admitted to Intensive Care Unit (ICU) and 233 patients to ordinary department. The median length of hospital stay was 20 days (Inter-Quartile-Range 13-32). Most patients (317/361, 87.8%) were still symptomatic at discharge, with one third referring three or more SC. At follow up, 67.3% (243/361) of patients still complained at least one SC. Moreover, 159 patients (44%) developed at least one new involved SC during follow up: 116 (72.9%) one SC, 39 (24.5%) two SC, 4 (2.5%) three or more SC. At follow up visit 130 of 361 (36%) were still with SC developed during follow up. At multivariable analysis presence of any SC at follow-up was associated with male gender (Odds Ratio [OR] 3.23, Confidence Interval [CI] 95% 1.46-7.15), ICU admission (OR 2.78, CI 95% 1.29-5.96) and presence of SC at discharge (OR 14.39, CI 95% 6.41-32.32).

CONCLUSIONS: In our sample of patients with severe COVID-19, we found that PCC are highly variable and fluctuating over time; in particular, in about 50% of our patients new SC appear during follow up. Moreover, presence of PCC also in patients without SC at discharge and the variability of symptoms underlining the advisability of our multidisciplinary approach.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04424992, registered on 28 February 2020 https://www.

CLINICALTRIALS: gov/ct2/results?recrs=ab&cond=&term=NCT04424992&cntry=&state=&city=&dist   The current version of protocol is version 1.0 enrolling since June 2020. The enrollment is still ongoing.}, } @article {pmid36693071, year = {2023}, author = {Haneef, R and Fayad, M and Fouillet, A and Sommen, C and Bonaldi, C and Wyper, GMA and Pires, SM and Devleesschauwer, B and Rachas, A and Constantinou, P and Levy-Bruhl, D and Beltzer, N and Gallay, A}, title = {Direct impact of COVID-19 by estimating disability-adjusted life years at national level in France in 2020.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280990}, pmid = {36693071}, issn = {1932-6203}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; Disability-Adjusted Life Years ; Quality-Adjusted Life Years ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Disabled Persons ; France/epidemiology ; }, abstract = {BACKGROUND: The World Health Organization declared a pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on March 11, 2020. The standardized approach of disability-adjusted life years (DALYs) allows for quantifying the combined impact of morbidity and mortality of diseases and injuries. The main objective of this study was to estimate the direct impact of COVID-19 in France in 2020, using DALYs to combine the population health impact of infection fatalities, acute symptomatic infections and their post-acute consequences, in 28 days (baseline) up to 140 days, following the initial infection.

METHODS: National mortality, COVID-19 screening, and hospital admission data were used to calculate DALYs based on the European Burden of Disease Network consensus disease model. Scenario analyses were performed by varying the number of symptomatic cases and duration of symptoms up to a maximum of 140 days, defining COVID-19 deaths using the underlying, and associated, cause of death.

RESULTS: In 2020, the estimated DALYs due to COVID-19 in France were 990 710 (1472 per 100 000), with 99% of burden due to mortality (982 531 years of life lost, YLL) and 1% due to morbidity (8179 years lived with disability, YLD), following the initial infection. The contribution of YLD reached 375%, assuming the duration of 140 days of post-acute consequences of COVID-19. Post-acute consequences contributed to 49% of the total morbidity burden. The contribution of YLD due to acute symptomatic infections among people younger than 70 years was higher (67%) than among people aged 70 years and above (33%). YLL among people aged 70 years and above, contributed to 74% of the total YLL.

CONCLUSIONS: COVID-19 had a substantial impact on population health in France in 2020. The majority of population health loss was due to mortality. Men had higher population health loss due to COVID-19 than women. Post-acute consequences of COVID-19 had a large contribution to the YLD component of the disease burden, even when we assume the shortest duration of 28 days, long COVID burden is large. Further research is recommended to assess the impact of health inequalities associated with these estimates.}, } @article {pmid36693032, year = {2023}, author = {Kimura, RH and Sharifi, H and Shen, B and Berry, GJ and Guo, HH}, title = {αvβ6 Integrin Positron Emission Tomography of Lung Fibrosis in Idiopathic Pulmonary Fibrosis and Long COVID-19.}, journal = {American journal of respiratory and critical care medicine}, volume = {207}, number = {12}, pages = {1633-1635}, doi = {10.1164/rccm.202206-1107IM}, pmid = {36693032}, issn = {1535-4970}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/diagnostic imaging ; *Idiopathic Pulmonary Fibrosis/diagnostic imaging ; Positron-Emission Tomography ; Antigens, Neoplasm ; }, } @article {pmid36692636, year = {2023}, author = {Ferrucci, R and Cuffaro, L and Capozza, A and Rosci, C and Maiorana, N and Groppo, E and Reitano, MR and Poletti, B and Ticozzi, N and Tagliabue, L and Silani, V and Priori, A}, title = {Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.}, journal = {Journal of neurology}, volume = {270}, number = {4}, pages = {1823-1834}, pmid = {36692636}, issn = {1432-1459}, mesh = {Male ; Humans ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; *COVID-19/complications/diagnostic imaging ; Brain/diagnostic imaging/metabolism ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18/metabolism ; Cognition ; *Alzheimer Disease/metabolism ; *Cognitive Dysfunction/diagnostic imaging/etiology/metabolism ; }, abstract = {Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain ([18]F-FDG) PET/CT, and one also underwent [18]F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an [18]F-amyloid PET/CT to assess the presence of Aβ plaques. This examination showed significant Aβ deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.}, } @article {pmid36691834, year = {2023}, author = {Ceban, F and Subramaniapillai, M and Rosenblat, JD and Mansur, RB and McIntyre, RS}, title = {Can COVID-19 have a clinically significant effect on drug metabolism?.}, journal = {Expert opinion on drug safety}, volume = {22}, number = {1}, pages = {1-3}, doi = {10.1080/14740338.2023.2172158}, pmid = {36691834}, issn = {1744-764X}, mesh = {Humans ; *COVID-19 ; Vaccination ; }, } @article {pmid36691205, year = {2022}, author = {Salci, MA and Carreira, L and Facchini, LA and Oliveira, MLF and de Oliveira, RR and Ichisato, SMT and Covre, ER and Pesce, GB and Santos, JAT and Derhun, FM and Hungaro, AA and Moura, D and Höring, CF and Santos, MLAD and Oliveira, NN and Paiano, M and Góes, HLF and Jaques, AE and Fernandes, CAM and Vissoci, JRN}, title = {Post-acute COVID and long-COVID among adults and older adults in the State of Paraná, Brazil: protocol for an ambispective cohort study.}, journal = {BMJ open}, volume = {12}, number = {9}, pages = {e061094}, pmid = {36691205}, issn = {2044-6055}, mesh = {Humans ; Aged ; Adolescent ; *COVID-19 ; SARS-CoV-2 ; Brazil/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Prospective Studies ; Retrospective Studies ; }, abstract = {INTRODUCTION: Since 2020, the world has been going through a viral pandemic with a high morbidity and mortality rate along with the potential to evolve from an acute infection to post-acute and long-COVID, which is still in the process of elucidation. Diagnostic and prognostic research is essential to understand the complexity of factors and contexts involving the illness's process. This protocol introduces a study strategy to analyse predictors, sequelae, and repercussions of COVID-19 in adults and older adults with different disease severities in the State of Paraná, Brazil.

METHODS AND ANALYSIS: A mixed-methods sequential explanatory design. The quantitative data will be conducted by an ambispective cohort study, which will explore the manifestations of COVID-19 for 18 months, with nearly 3000 participants with confirmed diagnoses of COVID-19 (reverse transcription-PCR test) between March and December of 2020, retrieved from national disease reporting databases, over 18 years old, living in a Brazilian State (Paraná) and who survived the viral infection after being discharged from a health service. Data collection will be conducted through telephone interviews, at two different occasions: the first will be a recall 12 months after the acute phase as a retrospective follow-up, and the second will be another prospective interview, with data of the following 6 months. For the qualitative step, Grounded Theory will be used; participants will be selected from the cohort population. The first sample group will be composed of people who were discharged from the intensive care unit, and other sample groups will be composed according to theoretical saturation. The qualitative data will follow the temporal design and classification of the disease provided for in the cohort.

ETHICS AND DISSEMINATION: Ethics approval was granted by the State University of Maringá, under opinion number: 4 165 272 and CAAE: 34787020.0.0000.0104 on 21 July 2020, and Hospital do Trabalhador (Worker's Hospital), which is accountable for the Health Department of the State of Paraná, under opinion number: 4 214 589 and CAAE: 34787020.0.3001.5225 on 15 August 2020. The participants will verbally consent to the research, their consent will be recorded, and the informed consent form will be sent by mail or email. Outcomes will be widely disseminated through peer-reviewed manuscripts, conference presentations, media and reports to related authorities.}, } @article {pmid36690948, year = {2023}, author = {Shanbehzadeh, S and Zanjari, N and Yassin, M and Yassin, Z and Tavahomi, M}, title = {Association between long COVID, functional activity, and health-related quality of life in older adults.}, journal = {BMC geriatrics}, volume = {23}, number = {1}, pages = {40}, pmid = {36690948}, issn = {1471-2318}, mesh = {Humans ; Aged ; Aged, 80 and over ; *Quality of Life ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Activities of Daily Living ; Pain ; Fatigue ; }, abstract = {BACKGROUND: Older adults experience persistent symptoms post-COVID-19, termed as Long COVID, affecting their physical and mental health. This study aimed to evaluate the effects of Long COVID, level of physical activity, and functional decline on older adults' health-related quality of life post-COVID-19.

METHODS: This cross-sectional study was conducted on 121 older adults with 60 to 90 years old post-coronavirus infection. The standardized metrics used in the study were Fatigue Severity Scale, Physical Activity Elderly, SF12, Post-COVID-19 functional status scale, and COVID-19 Yorkshire rehabilitation screening scale. The severity of coronavirus infection was evaluated by changes in chest CT scan images and O2 saturation at hospital admission. Data were analyzed using linear regression analyses.

RESULTS: The results of regression analysis revealed six factors to be predictors of physical health at 6 months post-COVID-19 (F = 9.046, P < 0.001; explained variance 63%), which the significant factors were fatigue, level of physical activity, worsened pain, difficulties in activities of daily living and cognitive-communication problems. Among these factors, greater fatigue and worsened pain intensity were the strongest predictors. Mental health was associated with days of hospitalization and cognitive-communication problems (F = 2.866, P < 0.001; explained variance 35%).

CONCLUSIONS: Considering the negative impact of fatigue, pain, low physical activity, and cognitive-communication problems on health-related quality of life, early and accurate evaluation and management are required for recovered older adults post-COVID-19.}, } @article {pmid36690496, year = {2023}, author = {Klocke, C and Valentini, J and Stolz, R and Gaßner, L and Joos, S and Förster, C}, title = {Patients' Experiences With Therapeutic Approaches for Post-COVID Syndrome: Results of a Crowdsourced Research Survey.}, journal = {Annals of family medicine}, volume = {21}, number = {1}, pages = {73-75}, pmid = {36690496}, issn = {1544-1717}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Crowdsourcing ; Communication ; }, abstract = {Some patients develop multiple protracted sequelae after infection with SARS-CoV-2, collectively known as post-COVID syndrome or long COVID. To date, there is no evidence showing benefit of specific therapies for this condition, and patients likely resort to self-initiated therapies. We aimed to obtain information about therapies used by and needs of this population via inductive crowdsourcing research. Patients completed an online questionnaire about their symptoms and experiences with therapeutic approaches. Responses of 499 participants suggested few approaches (eg, mind-body medicine, respiratory therapy) had positive effects and showed a great need for patient-centered communication (eg, more recognition of this syndrome). Our findings can help design clinical studies and underscore the importance of the holistic approach to care provided by family medicine.}, } @article {pmid36690284, year = {2023}, author = {Ashton, RE and Philips, BE and Faghy, M}, title = {The acute and chronic implications of the COVID-19 virus on the cardiovascular system in adults: A systematic review.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {31-37}, pmid = {36690284}, issn = {1873-1740}, mesh = {Humans ; Adult ; SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Heart ; *Cardiovascular Diseases/diagnosis/epidemiology ; }, abstract = {Despite coronavirus disease 2019 (COVID-19) primarily being identified as a respiratory illness, some patients who seemingly recovered from initial infection, developed chronic multi-system complications such as cardiovascular (CV), pulmonary and neurological issues leading to multiple organ injuries. However, to date, there is a dearth of understanding of the acute and chronic implications of a COVID-19 infection on the CV system in adults. A systematic review of the literature was conducted according to PRISMA guidelines and prospectively registered via Prospero (ID: CRD42022360444). The MEDLINE Ovid, Cochrane Library and PubMed databases were searched from inception to August 2022. The search strategy keywords and MeSH terms used included: 1) COVID; 2) coronavirus; 3) long COVID; 4) cardiovascular; and 5) cardiovascular disease. Reference lists of all relevant systematic reviews identified were searched for additional studies. A total of 11,332 records were retrieved from database searches, of which 310 records were duplicates. A further 9887 were eliminated following screening of titles and abstracts. After full-text screening of 1135 articles, 9 manuscripts were included for review. The evidence of CV implications post-COVID-19 infection is clear, and this must be addressed with appropriate management strategies that recognise the acute and chronic nature of cardiac injury in COVID-19 patients. Efficacious management strategies will be needed to address long standing issues and morbidity.}, } @article {pmid36687403, year = {2022}, author = {Sum, CH and Ching, JYL and Song, T and Cheong, PK and Lo, CW and Lai, MK and Chia, CP and Chan, KL and Mak, WY and Leung, KC and Leung, SB and Zhang, H and Lin, Z}, title = {Chinese medicine for residual symptoms of COVID-19 recovered patients (long COVID)-A double-blind, randomized, and placebo-controlled clinical trial protocol.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {990639}, pmid = {36687403}, issn = {2296-858X}, abstract = {INTRODUCTION: Coronavirus disease 2019 (COVID-19) is the current global pandemic of which residual symptoms exhibited by post-acute, rehabilitating patients include fatigue, dyspnoea, and insomnia. Chinese medicine (CM) has been widely used in China to treat different stages of COVID-19. While there are a significant number of clinical studies suggesting its efficacy and safety in its use during acute stage, there are very few randomized controlled trials focusing on the rehabilitation stage. Liujunzhi Decoction and Shashen Maidong Decoction are frequently recommended by official clinical guidelines in China to treat COVID-19 patients in rehabilitation stage. This double-blind, randomized, placebo controlled study aims to evaluate the efficacy and safety of the combination of the two formulae [named "COVID-19 Rehab Formula (CRF)"] in treating COVID-19 residual symptoms (long COVID).

METHODS: Eligible subjects will be randomly divided into treatment group and control group in 1:1 ratio. Treatment group will receive CRF along with certain pre-defined CM according to symptoms for 8 weeks, while control group will receive equivalent packs of placebo for 8 weeks. Data in terms of Fatigue Severity Score (FSS), self-reported COVID-19 long term symptom assessment, the modified British Medical Research Council (mMRC) Dyspnoea Scale, EuroQol Five-Dimension Five-Level (EQ-5D-5L) Questionnaire, pulmonary function test and adverse events will be collected and analyzed by SPSS 24. Blood test on liver and renal functions will also be conducted as safety measures.

CONCLUSION: This study will evaluate the efficacy and safety of CRF in the treatment COVID-19 residual symptoms in a scientifically rigorous design.

CLINICAL TRIAL REGISTRATION: [ClinicalTrials.gov], identifier [NCT04924881].}, } @article {pmid36686632, year = {2023}, author = {Baskett, WI and Qureshi, AI and Shyu, D and Armer, JM and Shyu, CR}, title = {COVID-Specific Long-term Sequelae in Comparison to Common Viral Respiratory Infections: An Analysis of 17 487 Infected Adult Patients.}, journal = {Open forum infectious diseases}, volume = {10}, number = {1}, pages = {ofac683}, pmid = {36686632}, issn = {2328-8957}, abstract = {BACKGROUND: A better understanding of long-term health effects after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the health care priorities in the current pandemic. We analyzed a large and diverse patient cohort to study health effects related to SARS-CoV-2 infection occurring >1 month postinfection.

METHODS: We analyzed 17 487 patients who received diagnoses for SARS-CoV-2 infection in a total of 122 health care facilities in the United States before April 14, 2022. Patients were propensity score-matched with patients diagnosed with the common cold, influenza, or viral pneumonia from March 1, 2020, to April 1, 2021. For each outcome, SARS-CoV-2 was compared with a generic viral respiratory infection (VRI) by predicting diagnoses in the period between 30 and 365 days postinfection. Both coronavirus disease 2019 (COVID-19) and VRI patients were propensity score-matched with patients with no record of COVID-19 or VRI, and the same methodology was applied. Diagnoses where COVID-19 infection was a significant positive predictor in both COVID-19 vs VRI and COVID-19 vs control comparisons were considered COVID-19-specific effects.

RESULTS: Compared with common VRIs, SARS-CoV-2 was associated with diagnoses of palpitations, hair loss, fatigue, chest pain, dyspnea, joint pain, and obesity in the postinfectious period.

CONCLUSIONS: We identify that some diagnoses commonly described as "long COVID" do not appear significantly more frequent post-COVID-19 infection compared with other common VRIs. We also identify sequelae that are specifically associated with a prior SARS-CoV-2 infection.}, } @article {pmid36685609, year = {2023}, author = {Huerne, K and Filion, KB and Grad, R and Ernst, P and Gershon, AS and Eisenberg, MJ}, title = {Epidemiological and clinical perspectives of long COVID syndrome.}, journal = {American journal of medicine open}, volume = {9}, number = {}, pages = {100033}, pmid = {36685609}, issn = {2667-0364}, abstract = {Long COVID, or post-acute COVID-19 syndrome, is characterized by multi-organ symptoms lasting 2+ months after initial COVID-19 virus infection. This review presents the current state of evidence for long COVID syndrome, including the global public health context, incidence, prevalence, cardiopulmonary sequelae, physical and mental symptoms, recovery time, prognosis, risk factors, rehospitalization rates, and the impact of vaccination on long COVID outcomes. Results are presented by clinically relevant subgroups. Overall, 10-35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic stress disorder, memory loss, and difficulty concentrating. Delineating these issues will be crucial to inform appropriate post-pandemic health policy and protect the health of COVID-19 survivors, including potentially vulnerable or underrepresented groups. Directed to policymakers, health practitioners, and the general public, we provide recommendations and suggest avenues for future research with the larger goal of reducing harms associated with long COVID syndrome.}, } @article {pmid36685555, year = {2022}, author = {Sommen, SL and Havdal, LB and Selvakumar, J and Einvik, G and Leegaard, TM and Lund-Johansen, F and Michelsen, AE and Mollnes, TE and Stiansen-Sonerud, T and Tjade, T and Wyller, VBB and Berven, LL}, title = {Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1081718}, pmid = {36685555}, issn = {1664-3224}, mesh = {Humans ; Adolescent ; Young Adult ; *COVID-19 ; SARS-CoV-2 ; Cross-Sectional Studies ; Patient Acuity ; Biomarkers ; }, abstract = {INTRODUCTION: Both public and scientific attention have shifted from the acute COVID-19 illness to the chronic disability experienced by a proportion of COVID-19 convalescents. Post COVID-19 condition, a term used for long-lasting symptoms after COVID-19, can affect individuals across all disease severity and age groups. Data on post-COVID-19 symptomatology, epidemiology and pathophysiology in adolescents and young adults are scarce. To date, little is known on the immunological and pulmonary trends in these patients after COVID-19. This study investigated immunological markers and pulmonary function in non-hospitalized patients in this group at 6 months after initial mild COVID-19 infection.

METHODS: Non-hospitalized SARS-CoV-2 positive (n = 405) and SARS-CoV-2 negative (n = 111) adolescents and young adults (aged 12-25 years) were followed prospectively for six months after SARS-CoV-2 PCR testing. At baseline and at six months follow-up, all participants underwent an assessment including clinical examination, questionnaires, spirometry, and blood sampling. Cross-sectional comparisons of blood biomarkers; including white blood cell counts, CRP, GDF-15, a 27-multiplex cytokine assay, complement activation products and SARS-CoV-2 antibodies; and spirometry measures were performed after classification of all participants according to their COVID-19 status and adherence to post-COVID-19 case criteria. Associations between biomarkers and COVID-19 symptoms were explored.

RESULTS: No difference in pulmonary function was detected between the groups. COVID-19 convalescents had higher levels of chemokines eotaxin, MCP-1 and IP-10 than non-infected controls. The increase was modest and not associated with long-lasting COVID-19 symptoms.

DISCUSSION: Elevated inflammatory mediators were found in adolescents and young adults six months after mild COVID-19, but there was no association with post-COVID-19 condition.}, } @article {pmid36684985, year = {2022}, author = {Bowie, C and Friston, K}, title = {Using a Dynamic Causal Model to validate previous predictions and offer a 12-month forecast of the long-term effects of the COVID-19 epidemic in the UK.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1108886}, pmid = {36684985}, issn = {2296-2565}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; *Epidemics ; Models, Theoretical ; United Kingdom/epidemiology ; }, abstract = {BACKGROUND: Predicting the future UK COVID-19 epidemic provides a baseline of a vaccine-only mitigation policy from which to judge the effects of additional public health interventions. A previous 12-month prediction of the size of the epidemic to October 2022 underestimated its sequelae by a fifth. This analysis seeks to explain the reasons for the underestimation before offering new long-term predictions.

METHODS: A Dynamic Causal Model was used to identify changes in COVID-19 transmissibility and the public's behavioral response in the 12-months to October 2022. The model was then used to predict the future trends in infections, long-COVID, hospital admissions and deaths over 12-months to October 2023.

FINDINGS: The model estimated that the secondary attack rate increased from 0.4 to 0.5, the latent period shortened from 2.7 to 2.6 and the incubation period shortened from 2.0 to 1.95 days between October 2021 and October 2022. During this time the model also estimated that antibody immunity waned from 177 to 160 days and T-cell immunity from 205 to 180 days. This increase in transmissibility was associated with a reduction in pathogenicity with the proportion of infections developing acute respiratory distress syndrome falling for 6-2% in the same twelve-month period. Despite the wave of infections, the public response was to increase the tendency to expose themselves to a high-risk environment (e.g., leaving home) each day from 33-58% in the same period.The predictions for October 2023 indicate a wave of infections three times larger this coming year than last year with significant health and economic consequences such as 120,000 additional COVID-19 related deaths, 800,000 additional hospital admissions and 3.5 million people suffering acute-post-COVID-19 syndrome lasting more than 12 weeks.

INTERPRETATION: The increase in transmissibility together with the public's response provide plausible explanations for why the model underestimated the 12-month predictions to October 2022. The 2023 projection could well-underestimate the predicted substantial next wave of COVID-19 infection. Vaccination alone will not control the epidemic. The UK COVID-19 epidemic is not over. The results call for investment in precautionary public health interventions.}, } @article {pmid36682515, year = {2023}, author = {Erickson, MA and Logsdon, AF and Rhea, EM and Hansen, KM and Holden, SJ and Banks, WA and Smith, JL and German, C and Farr, SA and Morley, JE and Weaver, RR and Hirsch, AJ and Kovac, A and Kontsekova, E and Baumann, KK and Omer, MA and Raber, J}, title = {Blood-brain barrier penetration of non-replicating SARS-CoV-2 and S1 variants of concern induce neuroinflammation which is accentuated in a mouse model of Alzheimer's disease.}, journal = {Brain, behavior, and immunity}, volume = {109}, number = {}, pages = {251-268}, pmid = {36682515}, issn = {1090-2139}, support = {P30 AG066509/AG/NIA NIH HHS/United States ; RF1 AG059088/AG/NIA NIH HHS/United States ; R21 AG065928/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Blood-Brain Barrier/metabolism ; *Alzheimer Disease/metabolism ; SARS-CoV-2 ; *COVID-19/complications ; Neuroinflammatory Diseases ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 and especially Long COVID are associated with severe CNS symptoms and may place persons at risk to develop long-term cognitive impairments. Here, we show that two non-infective models of SARS-CoV-2 can cross the blood-brain barrier (BBB) and induce neuroinflammation, a major mechanism underpinning CNS and cognitive impairments, even in the absence of productive infection. The viral models cross the BBB by the mechanism of adsorptive transcytosis with the sugar N-acetylglucosamine being key. The delta and omicron variants cross the BB B faster than the other variants of concern, with peripheral tissue uptake rates also differing for the variants. Neuroinflammation induced by icv injection of S1 protein was greatly enhanced in young and especially in aged SAMP8 mice, a model of Alzheimer's disease, whereas sex and obesity had little effect.}, } @article {pmid36680925, year = {2023}, author = {Francis, G and Thunell, E}, title = {COVID-19 infection does not seem to affect cognition in college students.}, journal = {Consciousness and cognition}, volume = {108}, number = {}, pages = {103464}, pmid = {36680925}, issn = {1090-2376}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Bayes Theorem ; *COVID-19 ; Cognition/physiology ; Students/psychology ; }, abstract = {Emerging evidence indicates that COVID-19 damages the central nervous system and thereby might engender long-term cognitive impairment. Self-reports and some measures of cognitive ability suggest that long COVID can lead to substantial and frightening detriments in cognition. To further explore this issue, we used data from university courses on cognitive psychology where students participated in classic experiments that measure various aspects of cognition. Across 24 experiments we compared cognitive performance of students who had contracted COVID-19 against those who were uninfected. Using Bayes Factor analyses, we assessed both differences and invariances in performance as a function of infection status. Our findings suggest that COVID-19 infection has hardly any impact on cognition for university students.}, } @article {pmid36680646, year = {2023}, author = {Bowyer, RCE and Huggins, C and Toms, R and Shaw, RJ and Hou, B and Thompson, EJ and Kwong, ASF and Williams, DM and Kibble, M and Ploubidis, GB and Timpson, NJ and Sterne, JAC and Chaturvedi, N and Steves, CJ and Tilling, K and Silverwood, RJ and , }, title = {Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.}, journal = {European journal of epidemiology}, volume = {38}, number = {2}, pages = {199-210}, pmid = {36680646}, issn = {1573-7284}, support = {104036/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; 217065/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 216767/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MR/P023444/1/MRC_/Medical Research Council/United Kingdom ; WT212904/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_15018/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/3/MRC_/Medical Research Council/United Kingdom ; 221574/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; G9815508/MRC_/Medical Research Council/United Kingdom ; MR/W021315/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/2/MRC_/Medical Research Council/United Kingdom ; CS/16/4/32482/BHF_/British Heart Foundation/United Kingdom ; MR/N024397/1/MRC_/Medical Research Council/United Kingdom ; 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; WT101597MA/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Dyspnea ; Pain ; Fatigue ; United Kingdom ; }, abstract = {Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.}, } @article {pmid36680417, year = {2024}, author = {Salci, MA and Carreira, L and Baccon, WC and Marques, FRDM and Höring, CF and Oliveira, MLF and Milan, NS and de Souza, FCS and Gallo, AM and Covre, ER and Dixe, MA and Querido, A and Vissoci, JRN and Facchini, LA and Laranjeira, C}, title = {Perceived quality of life and associated factors in long COVID syndrome among older Brazilians: A cross-sectional study.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {178-191}, doi = {10.1111/jocn.16618}, pmid = {36680417}, issn = {1365-2702}, support = {//Ministério da Ciência, Tecnologia, Inovações e Comunicações - Brazil/ ; //Ministério da Saúde - Brazil/ ; 402882/2020-2//Conselho Nacional de Desenvolvimento Científico Tecnológico (CNPq) - Brazil/ ; CEECINST/00051/2018//FCT-Fundação para a Ciência e a Tecnologia - Portugal: Scientific Employment Stimulus-Institutional Call/ ; }, mesh = {*COVID-19/epidemiology ; *Post-Acute COVID-19 Syndrome/epidemiology ; South American People ; Humans ; *Quality of Life ; Aged ; Middle Aged ; Cross-Sectional Studies ; Brazil/epidemiology ; }, abstract = {AIMS AND OBJECTIVES: This paper aims to: (a) determine the personal, sociodemographic, clinical, behavioural, and social characteristics of older Brazilians with clinical evidence of long COVID; (b) evaluate perceived quality of life and determine its association with personal, sociodemographic, behavioural, clinical and social variables; and (c) assess significant predictors of high perceived QoL.

BACKGROUND: Given the inherent vulnerabilities of the ageing process, the older people are an at-risk group for both contagion of SARS-CoV-2 and the perpetuation of residual symptoms after infection, the so-called long COVID or post-COVID syndrome.

DESIGN: A cross-sectional survey design using the STROBE checklist.

METHODS: Brazilian older people with long COVID syndrome (n = 403) completed a phone survey measuring personal, sociodemographic, behavioural, clinical, and social characteristics, and perceived Quality of Life (QoL). Data were collected from June 2021-March 2022. A multiple linear regression model was performed to identify salient variables associated with high perceived QoL.

RESULTS: The mean age of participants was 67.7 ± 6.6 years old. The results of the multivariate regression model showed that race, home ownership, daily screen time, musculoskeletal and anxiety symptoms, and work situation were the significant predictors of QoL among COVID-19 survivors.

CONCLUSIONS: Knowledge about the persistence of physical, emotional, and social symptoms of COVID-19 can help nurses and other healthcare providers to improve the management of survivors, bringing benefits to the whole society.

Given the novelty of long-COVID and its heterogeneous trajectory, interventions focusing on the repercussions and requirements unique to more vulnerable older persons should be developed and these aspects should be included in public health recommendations and policymakers' concerns.

No patient or public contribution was required to design, to outcome measures or undertake this research. Patients/members of the public contributed only to the data collection.}, } @article {pmid36680296, year = {2023}, author = {Kirchberger, I and Peilstöcker, D and Warm, TD and Linseisen, J and Hyhlik-Dürr, A and Meisinger, C and Goßlau, Y}, title = {Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection.}, journal = {Viruses}, volume = {15}, number = {1}, pages = {}, pmid = {36680296}, issn = {1999-4915}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; *COVID-19/diagnosis ; SARS-CoV-2 ; *Cognitive Dysfunction/diagnosis/epidemiology/psychology ; Neuropsychological Tests ; }, abstract = {Studies on cognitive problems of persons with mild COVID-19 courses are still lacking. This study aimed to determine the frequency and associated factors of subjective and objective cognitive problems after COVID-19 in non-hospitalized persons. Study participants were examined at the University Hospital of Augsburg from 04/11/2020 to 26/05/2021. The Wechsler Adult Intelligence Scale (WAIS) IV digit span, Stroop Color and Word Test (SCWT), Regensburger verbal fluency test (RWT) and, subjective ratings of memory and concentration were applied. Of the 372 participants (mean age 46.8 ± 15.2 years, 54.3% women, median time after infection 9.1 months), 24.9% reported concentration and 21.9% memory problems. Overall, 55.6% of the participants had at least a mild negative alteration in any cognitive test. The strongest impairments were found regarding memory functions (41.1% mild alterations, 6.2% distinct impairments) and verbal fluency (12.4% mild alterations, 5.4% distinct impairments). SCWT showed negative alterations in no more than 3.0% of the participants. Level of school education, age, and depressiveness emerged as significantly related to the cognitive tests. The number of complaints and depressiveness were significantly associated with subjective memory and concentration problems. It is important to identify mild cognitive impairment in non-hospitalized COVID-19 patients early to offer them effective interventions.}, } @article {pmid36680082, year = {2022}, author = {Haque, A and Pant, AB}, title = {Long Covid: Untangling the Complex Syndrome and the Search for Therapeutics.}, journal = {Viruses}, volume = {15}, number = {1}, pages = {}, pmid = {36680082}, issn = {1999-4915}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {Long Covid can affect anyone who has previously had acute COVID-19. The root causes of this syndrome are still unknown, and no effective therapeutics are available. This complex syndrome, with a wide array of symptoms, is still evolving. Given the dire situation, it is important to identify the causes of Long Covid and the changes occurring within the immune system of affected patients to figure out how to treat it. The immune system intersects with the persistent viral fragments and blood clots that are implicated in this syndrome; understanding how these complex systems interact may help in untangling the puzzling physiopathology of Long Covid and identifying mitigation measures to provide patients some relief. In this paper, we discuss evidence-based findings and formulate hypotheses on the mechanisms underlying Long Covid's physiopathology and propose potential therapeutic options.}, } @article {pmid36676175, year = {2023}, author = {Di Stadio, A and Bernitsas, E and La Mantia, I and Brenner, MJ and Ralli, M and Vaira, LA and Colizza, A and Cavaliere, C and Laudani, M and Frohman, TC and De Vincentiis, M and Frohman, EM and Altieri, M}, title = {Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {36676175}, issn = {2075-1729}, abstract = {Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.}, } @article {pmid36676046, year = {2022}, author = {Sansone, D and Tassinari, A and Valentinotti, R and Kontogiannis, D and Ronchese, F and Centonze, S and Maggiore, A and Cegolon, L and Filon, FL}, title = {Persistence of Symptoms 15 Months since COVID-19 Diagnosis: Prevalence, Risk Factors and Residual Work Ability.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {36676046}, issn = {2075-1729}, abstract = {Background: A proportion of patients' ailments may last after recovering from acute COVID-19, with episodic and systemic symptoms of unclear etiology potentially involving different organs. Study aim: The aim of this study was to investigate the persistence of symptoms 15 months since COVID-19 diagnosis in patients referring to the post-COVID-19 clinic in Trieste (north-eastern Italy). Methods: Two-hundred-forty-seven patients were medically examined between 8 December 2020-6 April 2021, after a median time of 49 days since first positive swab test for SARS-CoV-2. After a median time of 15 months since COVID-19 diagnosis, the same patients were contacted over the phone and investigated by standardized questionnaire collecting information on any persisting symptoms and work ability index (WAI). Four multivariable logistic regression models were fitted to investigate factors associated with persistence of any respiratory, neurological, dysautonomic, or psychiatric symptoms at first (median time 49 days since COVID-19 diagnosis) as well as second (median 15 months since COVID-19 diagnosis) follow up. A multiple linear regression was also employed to investigate factors associated with higher mean WAI, assessed only at second follow up. Additionally, factors associated with persistence of symptoms 200+ days since COVID-19 diagnosis between first and second follow-up were investigated by multivariable Generalized Estimating Equation (GEE). Results: At first follow up (median time of 49 days since COVID-19 diagnosis) symptoms more frequently reported were fatigue (80.2%), shortness of breath (69.6%), concentration deficit (44.9%), headache (44.9%), myalgia (44.1%), arthralgia (43.3%), and anosmia (42.1%). At second follow-up (median time of 15 months since COVID-19 diagnosis) 75% patients returned to their baseline status preceding COVID-19. At first follow up males were less likely to experience neurological (OR = 0.16; 95% CI: 0.08; 0.35) as well as psychiatric (OR = 0.43; 95% CI: 0.23; 0.80) symptoms as compared to females. At first follow up, the risk of neurological symptoms increased also linearly with age (OR = 1.04; 95% CI: 1.01; 1.08) and pre-existing depression was a major risk factor for persisting dysautonomic (aOR = 6.35; 95% CI: 2.01; 20.11) as well as psychiatric symptoms (omitted estimate). Consistently, at second follow up only females experience psychiatric symptoms, whereas males exhibited significantly higher mean WAI (RC = 0.50; 95% CI: 0.11; 0.88). Additionally, neurological symptoms at second follow up were more likely in patients with pre-existing comorbidities (OR = 4.31; 95% CI: 1.27; 14.7). Finally, persistence of symptoms lasting 200+ days since COVID-19 diagnosis increased linearly with age (OR = 1.03; 95% CI 1.01-1.05) and were more likely in patients affected by pre-existing depression (OR = 2.68; 95% CI 1.60; 4.49). Conclusions: Following a median time of 15 months since first positive swab test, 75% patients with symptoms returned to their baseline health status preceding COVID-19. Females had a significantly lower WAI and were more likely to experience psychiatric symptoms at second follow up (15 months since COVID-19 diagnosis). Furthermore, the risk of symptoms persisting 200+ days since COVID-19 diagnosis increased with history of depression, endorsing the hypothesis that long-COVID-19 symptoms may be at least partially explained by pre-existing psychological conditions. Patient rehabilitation and psychological support may therefore play a key role in caring patients with the so called long COVID-19 syndrome.}, } @article {pmid36675555, year = {2023}, author = {De Maria, L and Sponselli, S and Caputi, A and Stefanizzi, P and Pipoli, A and Giannelli, G and Delvecchio, G and Tafuri, S and Inchingolo, F and Migliore, G and Bianchi, FP and Boffetta, P and Vimercati, L}, title = {SARS-CoV-2 Breakthrough Infections in Health Care Workers: An Italian Retrospective Cohort Study on Characteristics, Clinical Course and Outcomes.}, journal = {Journal of clinical medicine}, volume = {12}, number = {2}, pages = {}, pmid = {36675555}, issn = {2077-0383}, abstract = {BACKGROUND: The aim of this study was to determine the characteristics, clinical course and outcomes of COVID-19 breakthrough infections (BIs) among healthcare workers (HCWs) of an Italian University Hospital.

METHODS: A retrospective observational study was conducted on 6111 HCWs, from January 2021 to February 2022. The study population was offered the full vaccination with BNT162b2 mRNA COVID-19 vaccine. To allow return to work after BI, the protocol required one negative nasopharyngeal RT-PCR swab followed by a medical examination to assess the HCW's health status. Laboratory tests, instrumental tests and specialist evaluations were carried out if necessary.

RESULTS: The cases of BIs observed numbered 582 (9.7%). The frequency of BIs was significantly higher in females than in males (67% vs. 33%; p = 0.03), and in nurses than in all other professional categories (p = 0.001). A total of 88% of the HCWs affected by BI were still symptomatic after the negative swab. None of the instrumental tests carried out showed any new findings of pathological significance. All cases showed progressive disappearance of symptoms, such that no cases of long COVID and no hospitalization or deaths were recorded.

CONCLUSIONS: Our results confirm that SARS-CoV-2 infections occur even after a full vaccination course; however, the clinical course is favorable and severe outcomes are reduced.}, } @article {pmid36675479, year = {2023}, author = {Zhang, Q and Ye, Z and Bignotti, A and Zheng, XL}, title = {Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19.}, journal = {Journal of clinical medicine}, volume = {12}, number = {2}, pages = {}, pmid = {36675479}, issn = {2077-0383}, abstract = {Background: Endotheliopathy is a common pathologic finding in patients with acute and long COVID-19. It may be associated with disease severity and predispose patients to long-term complications. Plasma levels of a proteoglycan, syndecan-1, are found to be significantly elevated in patients with COVID-19, but its roles in assessing disease severity and predicting long-term outcome are not fully understood. Methods: A total of 124 consecutive hospitalized patients with SARS-CoV-2 infection were prospectively enrolled and blood samples were collected on admission (T1), 3−4 days following treatment (T2), and 1−2 days prior to discharge or death (T3). Plasma levels of syndecan-1 were determined using an immunosorbent assay; various statistical analyses were performed to determine the association between plasma syndecan-1 levels and disease severity or the 60-day mortality rate. Results: Compared with those in the healthy controls, plasma levels of syndecan-1 in patients with critical COVID-19 were significantly higher (p < 0.0001). However, there was no statistically significant difference among patients with different disease severity (p > 0.05), resulting from large individual variability. Longitudinal analysis demonstrated that while the levels fluctuated during hospitalization in all patients, plasma syndecan-1 levels were persistently elevated from baseline in critical COVID-19 patients. Cox proportional hazard regression analyses revealed that elevated plasma levels of syndecan-1 (>260 ng/mL at T1, >1018 ng/mL at T2, and >461 ng/mL at T3) were significantly associated with the 60-day mortality rate. Conclusions: Endotheliopathy, marked by glycocalyx degradation and elevated plasma syndecan-1, occurs in nearly all hospitalized patients with SARS-CoV-2 infection; elevated plasma syndecan-1 is associated with increased mortality in COVID-19 patients.}, } @article {pmid36675440, year = {2023}, author = {Al-Hakeim, HK and Al-Rubaye, HT and Almulla, AF and Al-Hadrawi, DS and Maes, M}, title = {Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.}, journal = {Journal of clinical medicine}, volume = {12}, number = {2}, pages = {}, pmid = {36675440}, issn = {2077-0383}, abstract = {BACKGROUND: Long-term coronavirus disease 2019 (long COVID) is associated with physio-somatic (chronic fatigue syndrome and somatic symptoms) and affective (depression and anxiety) symptoms. The severity of the long COVID physio-affective phenome is largely predicted by increased peak body temperature (BT) and lowered oxygen saturation (SpO2) during the acute infectious phase. This study aims to delineate whether the association of BT and SpO2 during the acute phase and the long COVID physio-affective phenome is mediated by neurotoxicity (NT) resulting from activated immune-inflammatory and oxidative stress pathways.

METHODS: We recruited 86 patients with long COVID (3-4 months after the acute phase) and 39 healthy controls and assessed serum C-reactive protein (CRP), caspase 1, interleukin (IL) 1β, IL-18, IL-10, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and calcium (Ca), as well as peak BT and SpO2 during the acute phase.

RESULTS: Cluster analysis revealed that a significant part (34.9%) of long COVID patients (n = 30) show a highly elevated NT index as computed based on IL-1β, IL-18, caspase 1, CRP, MPO, and AOPPs. Partial least squares analysis showed that 61.6% of the variance in the physio-affective phenome of long COVID could be explained by the NT index, lowered Ca, and peak BT/SpO2 in the acute phase and prior vaccinations with AstraZeneca or Pfizer. The most important predictors of the physio-affective phenome are Ca, CRP, IL-1β, AOPPs, and MPO.

CONCLUSION: The infection-immune-inflammatory core of acute COVID-19 strongly predicts the development of physio-affective symptoms 3-4 months later, and these effects are partly mediated by neuro-immune and neuro-oxidative pathways.}, } @article {pmid36675349, year = {2023}, author = {Ostrowska, M and Rzepka-Cholasińska, A and Pietrzykowski, Ł and Michalski, P and Kosobucka-Ozdoba, A and Jasiewicz, M and Kasprzak, M and Kryś, J and Kubica, A}, title = {Effects of Multidisciplinary Rehabilitation Program in Patients with Long COVID-19: Post-COVID-19 Rehabilitation (PCR SIRIO 8) Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {2}, pages = {}, pmid = {36675349}, issn = {2077-0383}, abstract = {Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 (p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients.}, } @article {pmid36675242, year = {2023}, author = {Giannitrapani, L and Mirarchi, L and Amodeo, S and Licata, A and Soresi, M and Cavaleri, F and Casalicchio, S and Ciulla, G and Ciuppa, ME and Cervello, M and Barbagallo, M and Veronese, N and The Comepa Group, }, title = {Can Baseline IL-6 Levels Predict Long COVID in Subjects Hospitalized for SARS-CoV-2 Disease?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36675242}, issn = {1422-0067}, support = {FFR 2021//University of Palermo/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Interleukin-6 ; Hospitalization ; }, abstract = {The immune response to infection plays a crucial role in the pathogenesis of COVID-19, but several patients develop a wide range of persistent symptoms, which is becoming a major global health and economic burden. However, reliable indicators are not yet available to predict the persistence of symptoms typical of the so-called long COVID. Our study aims to explore an eventual role of IL-6 levels as a marker of long COVID. Altogether, 184 patients admitted to the COVID Medicine Unit of the University Hospital in Palermo, Italy, from the 1st of September 2020, were analyzed. Patients were divided into two groups according to the IL-6 serum levels (normal or elevated), considering the serum IL-6 levels measured during the first four days of hospitalization. In our study, higher serum IL-6 levels were associated with a doubled higher risk of long COVID (OR = 2.05; 95% CI: 1.04-4.50) and, in particular, they were associated with a higher incidence of mobility decline (OR = 2.55; 95% CI: 1.08-9.40) and PTSD (OR = 2.38; 95% CI: 1.06-8.61). The analysis of our case series confirmed the prominent role of IL-6 levels in response to SARS-CoV-2 infection, as predictors not only of COVID-19 disease severity and unfavorable outcomes, but also long COVID development trends.}, } @article {pmid36674665, year = {2023}, author = {Vasichkina, E and Alekseeva, D and Kudryavtsev, I and Glushkova, A and Starshinova, AY and Malkova, A and Kudlay, D and Starshinova, A}, title = {COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674665}, issn = {1422-0067}, support = {075-15-2022-301//Federal Almazov North-West Medical Research Centre/ ; }, mesh = {Adult ; *Myocarditis/diagnosis ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; *COVID-19/complications/diagnosis ; Humans ; COVID-19 Testing ; Post-Acute COVID-19 Syndrome ; }, abstract = {In the beginning of COVID-19, the proportion of confirmed cases in the pediatric population was relatively small and there was an opinion that children often had a mild or asymptomatic course of infection. Our understanding of the immune response, diagnosis and treatment of COVID-19 is highly oriented towards the adult population. At the same time, despite the fact that COVID-19 in children usually occurs in a mild form, there is an incomplete understanding of the course as an acute infection and its subsequent manifestations such as Long-COVID-19 or Post-COVID-19, PASC in the pediatric population, correlations with comorbidities and immunological changes. In mild COVID-19 in childhood, some authors explain the absence of population decreasing T and B lymphocytes. Regardless of the patient's condition, they can have the second phase, related to the exacerbation of inflammation in the heart tissue even if the viral infection was completely eliminated-post infectious myocarditis. Mechanism of myocardial dysfunction development in MIS-C are not fully understood. It is known that various immunocompetent cells, including both resident inflammatory cells of peripheral tissues (for example macrophages, dendritic cells, resident memory T-lymphocytes and so on) and also circulating in the peripheral blood immune cells play an important role in the immunopathogenesis of myocarditis. It is expected that hyperproduction of interferons and the enhanced cytokine response of T cells 1 and 2 types contribute to dysfunction of the myocardium. However, the role of Th1 in the pathogenesis of myocarditis remains highly controversial. At the same time, the clinical manifestations and mechanisms of damage, including the heart, both against the background and after COVID-19, in children differ from adults. Further studies are needed to evaluate whether transient or persistent cardiac complications are associated with long-term adverse cardiac events.}, } @article {pmid36674238, year = {2023}, author = {da Costa E Silva, GR and Moura, WÉA and Dos Santos, KC and Gomes, DO and Bandeira, GN and Guimarães, RA and Rosso, CFW and Bazilio, GS and Leite, VRMC and Caetano, KAA and Carneiro, MADS and Teles, SA}, title = {Long-Term Symptoms after Mild Coronavirus Disease in Healthy Healthcare Professionals: A 12-Month Prospective Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {2}, pages = {}, pmid = {36674238}, issn = {1660-4601}, mesh = {Adult ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Myalgia ; Anosmia ; Cough/epidemiology ; Prospective Studies ; Headache/epidemiology/etiology ; *Pharyngitis/epidemiology ; Health Personnel ; Fatigue/epidemiology/etiology ; Delivery of Health Care ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has changed the course of human history and killed millions of people worldwide. Its long-term consequences remain uncertain. This study aimed to describe the short- and long-term symptoms of COVID-19 among individuals in Goiás, central Brazil, who experienced acute mild or non-symptomatic SARS-CoV-2 infection during the first wave of the pandemic. This prospective cohort study included 110 healthcare workers, 18 safety workers, and 19 administrative support workers, who were followed up for 12 months after the onset of COVID-19. Most participants were healthy adult female healthcare professionals. At the onset of infection, the major symptoms were headache, myalgia, nasal congestion, cough, coryza, anosmia, ageusia, sore throat, fatigue, diarrhea, and dyspnea. Furthermore, 20.3% of the participants had three or more COVID-19 symptoms that persisted for at least 12 months. These included coryza, congestion, hair loss, sore throat, headache, myalgia, cough, memory loss, anosmia, and fatigue. This study revealed a high prevalence of persistent symptoms of COVID-19 in healthy individuals from central Brazil, which may present an additional burden on healthcare services. Further studies are required to investigate the sequelae of COVID-19 over periods greater than 12 months.}, } @article {pmid36674117, year = {2023}, author = {Hausswirth, C and Schmit, C and Rougier, Y and Coste, A}, title = {Positive Impacts of a Four-Week Neuro-Meditation Program on Cognitive Function in Post-Acute Sequelae of COVID-19 Patients: A Randomized Controlled Trial.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {2}, pages = {}, pmid = {36674117}, issn = {1660-4601}, mesh = {Humans ; Quality of Life ; *Meditation ; Depression/etiology/therapy/psychology ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/therapy ; Cognition ; }, abstract = {Study objective: Long COVID patients can experience high levels of impairment in their cognitive function and mental health. Using a parallel randomized control trial, we evaluated the effectiveness of a neuro-meditation program to reduce cognitive impairment in patients with long COVID. Methods: A total of 34 patients with long COVID were randomized to an intervention group (G-Int; n = 17) or a control group (G-Con; n = 17) and 15 healthy participants were constitutive of a normative group (G-Nor). The intervention consisted of ten 30-min sessions of Rebalance® over a period of five weeks. Each session included sound therapy and coach-guided meditation associated with light stimulations (i.e., chromotherapy). Primary outcomes were performance on five computerized cognitive tasks (choice response time, pattern comparison, Simon, pursuit rotor task, and Corsi block-tapping task), mental and physical fatigue (Chalder fatigue scale), perceived stress (perceived stress scale) and mood (profiles of mood states). Secondary outcomes were anxiety and depressive symptoms (hospital anxiety and depression scale), muscular pain, joint pain, and headaches using visual analog scales (VAS) as well as sleep quality (Spiegel sleep questionnaire). Assessments were conducted at baseline and at 1−2 and 7−8 days of follow-up. Results: Compared to healthy subjects, long COVID patients showed significant differences at baseline on all the self-report questionnaires, and a Rebalance® program improved all the subjective reports, as well as cognitive performances, especially on reaction time-based tasks. In particular, only the G-Int group revealed shortened reaction times in the choice reaction time (RTbaseline = 593 ± 121 ms vs. RTpost2 = 521 ± 86 ms, p < 0.001), Simon (RTbaseline = 539 ± 123 ms vs. RTpost2 = 494 ± 134 ms, p < 0.01), and pattern comparison tasks (RTbaseline = 1244 ± 315 ms vs. RTpost2 = 1079 ± 213 ms, p < 0.001). Conclusions) Initial evidence suggests that neuro-meditation reduces cognitive impairment and improves physical and mental fatigue, muscle and joint pain, symptoms of depression and anxiety, mood disturbances as well as sleep quality. The Rebalance® program hence constitutes a promising non-pharmacological intervention for the treatment of long-term psychological/cognitive outcomes of COVID-19.}, } @article {pmid36673587, year = {2023}, author = {Romero-Rodríguez, E and Perula-de-Torres, LÁ and González-Lama, J and Castro-Jiménez, RÁ and Jiménez-García, C and Priego-Pérez, C and Vélez-Santamaría, R and Simón-Vicente, L and González-Santos, J and González-Bernal, JJ}, title = {Long COVID Symptomatology and Associated Factors in Primary Care Patients: The EPICOVID-AP21 Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {36673587}, issn = {2227-9032}, abstract = {Persistent COVID-19 condition includes a wide variety of symptoms and health problems of indeterminate duration. The present study examined the sociodemographic and clinical characteristics of the population with Long COVID seen in Primary Care using a questionnaire based on the existing scientific literature. It was an observational and descriptive study of the characteristics of the Spanish population with Long COVID over 14 years of age. The responses were analysed by means of a descriptive analysis of the variables recorded, in addition to a bivariate analysis to determine the existence of a relationship between persistent COVID-19 and variables such as gender, age, vaccination status or concomitant pathology. The results obtained clearly describe the sociodemographic characteristics of the population, highlighting the predominance of female gender and the prevalence of tiredness and fatigue. Furthermore, relevant information was obtained on the differences in symptomatology according to gender, age, previous pathologies and alterations derived from infection and/or vaccination. These data are important for better detection, diagnosis and treatment of Long COVID and the improvement of the quality of life of this population.}, } @article {pmid36673565, year = {2023}, author = {Guzman-Esquivel, J and Mendoza-Hernandez, MA and Guzman-Solorzano, HP and Sarmiento-Hernandez, KA and Rodriguez-Sanchez, IP and Martinez-Fierro, ML and Paz-Michel, BA and Murillo-Zamora, E and Rojas-Larios, F and Lugo-Trampe, A and Plata-Florenzano, JE and Delgado-Machuca, M and Delgado-Enciso, I}, title = {Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {36673565}, issn = {2227-9032}, support = {319282//Consejo Nacional de Ciencia y Tecnología/ ; }, abstract = {BACKGROUND: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID.

METHODS: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale.

RESULTS: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1-3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0-4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08-3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2-47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1-3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4-0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2-0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%).

CONCLUSIONS: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.}, } @article {pmid36673555, year = {2023}, author = {Valverde-Martínez, MÁ and López-Liria, R and Martínez-Cal, J and Benzo-Iglesias, MJ and Torres-Álamo, L and Rocamora-Pérez, P}, title = {Telerehabilitation, A Viable Option in Patients with Persistent Post-COVID Syndrome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {36673555}, issn = {2227-9032}, abstract = {The number of patients with post-COVID-19 syndrome continues to increase considerably, having serious healthcare, social and economic repercussions. The objective of this study is to describe the effectiveness of telerehabilitation to alleviate the symptoms of post-COVID-19 syndrome. A systematic review was conducted using the information available on four databases (PubMed, Medline, Scielo and PEDRo) on these patients until November 2022. The MeSH search terms were: Post-COVID syndrome, Post-COVID-19, Long COVID, Telerehabilitation, Physiotherapy, Rehabilitation, Virtual, Home care. Six articles were included which provided information on 140 patients, detailing their symptomatology, assessment, treatment and monitoring. The variables measured were dyspnea, fatigue, physical performance and quality of life. All studies included aerobic and anaerobic exercises. Most notable among the techniques used were rib cage expansion exercises, respiratory control and thoracic cage stretching, patient education, Mindfulness and virtual reality games to address physical, mental and relaxation aspects. The use of telerehabilitation could be an effective tool for the treatment of persistent symptoms after suffering from COVID-19. It has been shown in these studies that patients improve both their physical performance and their quality of life.}, } @article {pmid36672595, year = {2022}, author = {Brogna, C and Cristoni, S and Brogna, B and Bisaccia, DR and Marino, G and Viduto, V and Montano, L and Piscopo, M}, title = {Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2-New Data for a Possible Role in the Long COVID Pattern.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, pmid = {36672595}, issn = {2227-9059}, abstract = {It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson's disease (PD) or Alzheimer's Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.}, } @article {pmid36672005, year = {2022}, author = {Miskowiak, KW and Bech, JL and Henriksen, AC and Johnsen, S and Podlekareva, D and Marner, L}, title = {Cerebral Metabolic Rate of Glucose and Cognitive Tests in Long COVID Patients.}, journal = {Brain sciences}, volume = {13}, number = {1}, pages = {}, pmid = {36672005}, issn = {2076-3425}, abstract = {BACKGROUND: Common long-term sequelae after COVID-19 include fatigue and cognitive impairment. Although symptoms interfere with daily living, the underlying pathology is largely unknown. Previous studies report relative hypometabolism in frontal, limbic and cerebellar regions suggesting focal brain involvement. We aimed to determine whether absolute hypometabolism was present and correlated to same day standardized neurocognitive testing.

METHODS: Fourteen patients included from a long COVID clinic had cognitive testing and quantitative dynamic [[18]F]FDG PET of the brain on the same day to correlate cognitive function to metabolic glucose rate.

RESULTS: We found no hypometabolism in frontal, limbic and cerebellar regions in cognitively impaired relative to cognitive intact patients. In contrast, the cognitive impaired patients showed higher cerebellar metabolism (p = 0.03), which correlated with more severe deficits in working memory and executive function (p = 0.03).

CONCLUSIONS: Hypermetabolism in the cerebellum may reflect inefficient brain processing and play a role in cognitive impairments after COVID-19.}, } @article {pmid36671900, year = {2022}, author = {Khondakar, KR and Kaushik, A}, title = {Role of Wearable Sensing Technology to Manage Long COVID.}, journal = {Biosensors}, volume = {13}, number = {1}, pages = {}, pmid = {36671900}, issn = {2079-6374}, mesh = {Humans ; *COVID-19/diagnosis ; Post-Acute COVID-19 Syndrome ; *Wearable Electronic Devices ; Body Temperature ; Technology ; }, abstract = {Long COVID consequences have changed the perception towards disease management, and it is moving towards personal healthcare monitoring. In this regard, wearable devices have revolutionized the personal healthcare sector to track and monitor physiological parameters of the human body continuously. This would be largely beneficial for early detection (asymptomatic and pre-symptomatic cases of COVID-19), live patient conditions, and long COVID monitoring (COVID recovered patients and healthy individuals) for better COVID-19 management. There are multitude of wearable devices that can observe various human body parameters for remotely monitoring patients and self-monitoring mode for individuals. Smart watches, smart tattoos, rings, smart facemasks, nano-patches, etc., have emerged as the monitoring devices for key physiological parameters, such as body temperature, respiration rate, heart rate, oxygen level, etc. This review includes long COVID challenges for frequent monitoring of biometrics and its possible solution with wearable device technologies for diagnosis and post-therapy of diseases.}, } @article {pmid36671555, year = {2023}, author = {Righetto, I and Gasparotto, M and Casalino, L and Vacca, M and Filippini, F}, title = {Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.}, journal = {Biomolecules}, volume = {13}, number = {1}, pages = {}, pmid = {36671555}, issn = {2218-273X}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Brain-Gut Axis ; *Central Nervous System Diseases ; *Gastrointestinal Microbiome ; Mitochondria ; }, abstract = {Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and "Long-COVID". Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.}, } @article {pmid36670478, year = {2023}, author = {Garazzino, S and Denina, M and Pruccoli, G and Funiciello, E and Ramenghi, U and Fagioli, F}, title = {Long COVID-19/post-COVID condition in children: do we all speak the same language?.}, journal = {Italian journal of pediatrics}, volume = {49}, number = {1}, pages = {12}, pmid = {36670478}, issn = {1824-7288}, mesh = {Child ; Humans ; *COVID-19 ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Language ; }, abstract = {Post-COVID condition is a new and highly debated entity that is still to be outlined in its complexity, especially in the pediatric population. In response to the article by Trapani and colleagues, we report the results of a long-term follow-up conducted in the outpatient clinic of the Pediatric Infectious Diseases Unit on children admitted to our hospital with SARS-CoV-2 infection.}, } @article {pmid36670365, year = {2023}, author = {Kjellberg, A and Hassler, A and Boström, E and El Gharbi, S and Al-Ezerjawi, S and Kowalski, J and Rodriguez-Wallberg, KA and Bruchfeld, J and Ståhlberg, M and Nygren-Bonnier, M and Runold, M and Lindholm, P}, title = {Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {33}, pmid = {36670365}, issn = {1471-2334}, mesh = {Humans ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Hyperbaric Oxygenation/adverse effects ; Quality of Life ; Treatment Outcome ; Double-Blind Method ; }, abstract = {BACKGROUND: With ~ 50 million individuals suffering from post-COVID condition (PCC), low health related quality of life (HRQoL) is a vast problem. Common symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue, shortness of breath and cognitive dysfunction. No effective treatment options have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a candidate drug.

METHODS: The objective of this interim analysis is to describe our cohort and evaluate the safety of HBO2 for post covid condition. In an ongoing randomised, placebo-controlled, double blind, clinical trial, 20 previously healthy subjects with PCC were assigned to HBO2 or placebo. Primary endpoints are physical domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at 13 weeks. Secondary endpoints include objective physical tests. Safety endpoints are occurrence, frequency, and seriousness of Adverse Events (AEs). An independent data safety monitoring board (DSMB) reviewed unblinded data. The trial complies with Good Clinical Practice. Safety endpoints are evaluated descriptively. Comparisons against norm data was done using t-test.

RESULTS: Twenty subjects were randomised, they had very low HRQoL compared to norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs 83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs 662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there were at least a possible relationship with the study drug, most commonly cough and chest pain/discomfort.

CONCLUSIONS: An (unexpectedly) high frequency of AEs was observed but the DSMB assessed HBO2 to have a favourable safety profile. Our data may help other researchers in designing trials. Trial Registration ClinicalTrials.gov: NCT04842448. Registered 13 April 2021, https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30. Registered 21 May 2021, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.}, } @article {pmid36670030, year = {2023}, author = {García-Meléndez, DD and Morales-Casado, MI and Quintana Castro, P and Marsal Alonso, C}, title = {Persistent olfactory dysfunction in mild COVID-19 patients: A descriptive study of the characteristics and association with other symptoms.}, journal = {Medicina clinica}, volume = {160}, number = {8}, pages = {347-351}, pmid = {36670030}, issn = {1578-8989}, mesh = {Adult ; Humans ; *COVID-19/complications ; *Olfaction Disorders/diagnosis/epidemiology/etiology ; Prevalence ; Smell ; }, abstract = {INTRODUCTION: Post-COVID olfactory dysfunction continues to be studied due to the controversy of the mechanisms involved. The aim was to investigate the olfactory dysfunctions in association with other post-COVID symptoms.

MATERIAL AND METHODS: Observational, descriptive and single-center study. The patients had confirmed mild COVID-19 and subjective olfactory dysfunction of more than a month of evolution, which was assessed by Sniffin' Sticks Olfactory Test.

RESULTS: A total of 86 patients participated. The mean age was 37.2 years (SD 9.82). 70.9% reported parosmia and 46.5% symptoms of brain fog. A pathological test result was obtained in 72.1% of the participants. The most failed pen was 11 (apple) in 76.7%. Anosmia of pen 15 (anise) was reported more frequently in 24.4% and cacosmia of pen 9 (garlic) in 27.9%. We observed a significant association between patients who reported parosmias and brain fog (RR 2.18; p=0.018), also between parosmia and phantosmia (RR 6.042; p<0.001).

CONCLUSION: There is some pathological selectivity for certain test pens, a higher prevalence of cognitive symptoms and many patients with combined parosmia and brain fog.}, } @article {pmid36660968, year = {2023}, author = {Morello, R and Martino, L and Buonsenso, D}, title = {Diagnosis and management of post-COVID (Long COVID) in children: a moving target.}, journal = {Current opinion in pediatrics}, volume = {35}, number = {2}, pages = {184-192}, pmid = {36660968}, issn = {1531-698X}, mesh = {Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; Mental Health ; }, abstract = {PURPOSE OF REVIEW: This review describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge about its epidemiology, clinical presentation, pathogenesis and care.

RECENT FINDINGS: There is no internationally agreed definition of PCC, although now most researchers agree that it is a complex clinical symptomatology persisting for at least 3 months after COVID-19, without an alternative diagnosis. There are several uncertainties about paediatric PCC. So far, available literature suggest that 1-3% of recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop PCC. Its pathogenesis is unknown, although there is increasing evidence about possible abnormalities in the immune responses, cellular metabolism and intestinal microbiota, along with chronic endothelitis.

SUMMARY: Management of PCC in children is complex and require a multidisciplinary approach, with the goal of offering the best care possible to support diagnostics, research, mental health and access to research projects.}, } @article {pmid36660118, year = {2022}, author = {Jadali, Z and Jalil, AT}, title = {Long COVID and ophthalmology: New insights into underlying disease mechanisms.}, journal = {Taiwan journal of ophthalmology}, volume = {12}, number = {4}, pages = {499-500}, pmid = {36660118}, issn = {2211-5072}, } @article {pmid36657309, year = {2023}, author = {Versace, V and Tankisi, H}, title = {Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Potential neurophysiological biomarkers for these enigmatic entities.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {147}, number = {}, pages = {58-59}, pmid = {36657309}, issn = {1872-8952}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Biomarkers ; }, } @article {pmid36657113, year = {2022}, author = {Gallegos, M and Martino, P and Caycho-Rodríguez, T and Calandra, M and Razumovskiy, A and Arias-Gallegos, WL and Castro-Peçanha, V and Cervigni, M}, title = {What is post-COVID-19 syndrome? Definition and update.}, journal = {Gaceta medica de Mexico}, volume = {158}, number = {6}, pages = {442-446}, doi = {10.24875/GMM.M22000725}, pmid = {36657113}, issn = {0016-3813}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Latin America/epidemiology ; Public Health ; }, abstract = {This work addresses the origin and development of post-COVID-19 syndrome, which consists of the persistence of different symptoms over time as a consequence of SARS-CoV-2 infection. Based on a narrative review of the scientific literature, a brief analysis of the new term is made, specifying the conceptual definition, characteristic symptoms, the various implications for people's health, and the responses to specific care measures that have been implemented. It concludes with a wake-up call to the governments of Latin America and the Caribbean in order for care and surveillance to be provided to this public health problem.}, } @article {pmid36656830, year = {2023}, author = {Burton, C and Dawes, H and Goodwill, S and Thelwell, M and Dalton, C}, title = {Within and between-day variation and associations of symptoms in Long Covid: Intensive longitudinal study.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280343}, pmid = {36656830}, issn = {1932-6203}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Dizziness ; Pain ; Fatigue ; }, abstract = {BACKGROUND: People with Long Covid (Post Covid-19 Condition) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level.

METHODS AND FINDINGS: Intensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression. App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly autocorrelated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes. Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants.

CONCLUSION: Symptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.}, } @article {pmid36656776, year = {2023}, author = {Hadley, E and Yoo, YJ and Patel, S and Zhou, A and Laraway, B and Wong, R and Preiss, A and Chew, R and Davis, H and Chute, CG and Pfaff, ER and Loomba, J and Haendel, M and Hill, E and Moffitt, R and , }, title = {SARS-CoV-2 Reinfection is Preceded by Unique Biomarkers and Related to Initial Infection Timing and Severity: an N3C RECOVER EHR-Based Cohort Study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36656776}, support = {UM1 TR004404/TR/NCATS NIH HHS/United States ; U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {Although the COVID-19 pandemic has persisted for over 2 years, reinfections with SARS-CoV-2 are not well understood. We use the electronic health record (EHR)-based study cohort from the National COVID Cohort Collaborative (N3C) as part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative to characterize reinfection, understand development of Long COVID after reinfection, and compare severity of reinfection with initial infection. We validate previous findings of reinfection incidence (5.9%), the occurrence of most reinfections during the Omicron epoch, and evidence of multiple reinfections. We present novel findings that Long COVID diagnoses occur closer to the index date for infection or reinfection in the Omicron BA epoch. We report lower albumin levels leading up to reinfection and a statistically significant association of severity between first infection and reinfection (chi-squared value: 9446.2, p-value: 0) with a medium effect size (Cramer's V: 0.18, DoF = 4).}, } @article {pmid36655704, year = {2023}, author = {Hedin, K and van der Velden, AW and Hansen, MP and Moberg, AB and Balan, A and Bruno, P and Coenen, S and Johansen, E and Kowalczyk, A and Kurotschka, PK and van der Linde, SR and Malania, L and Rohde, J and Verbakel, J and Vornhagen, H and Vellinga, A}, title = {Initial symptoms and three months follow-up after acute COVID-19 in outpatients: An international prospective cohort study.}, journal = {The European journal of general practice}, volume = {29}, number = {2}, pages = {2154074}, pmid = {36655704}, issn = {1751-1402}, mesh = {Adult ; Humans ; *Outpatients ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Most studies on long-term follow-up of patients with COVID-19 focused on hospitalised patients. No prospective study with structured follow-up has been performed in non-hospitalised patients with COVID-19.

OBJECTIVES: To assess long-COVID and post-COVID (WHO definition: symptomatic at least 12 weeks), describe lingering symptoms, their impact on daily activities, and general practice visits and explore risk factors for symptom duration in outpatients.

METHODS: A prospective study of adult outpatients with confirmed SARS-CoV-2 infection and symptoms consistent with COVID-19 in 11 European countries, recruited during 2020 and 2021 from primary care and the community. Structured follow-up by phone interviews (symptom rating, symptom impact on daily activities and general practice visits) was performed at weeks 2, 4, 8, and 12 by study personnel. Data was analysed descriptively by using correlation matrixes and Cox regression.

RESULTS: Of 270 enrolled patients, 52% developed long-COVID and 32% post-COVID-syndrome. When only considering the presence of moderate or (very) severe symptoms at weeks 8 and 12, these percentages were 28% and 18%, respectively. Fatigue was the most often reported symptom during follow-up. The impact of lingering symptoms was most evident in sports and household activities. About half (53%) had at least one general practice contact during follow-up. Obese patients took twice as long to return to usual health (HR: 0.5, 95%CI: 0.3-0.8); no other risk profile could predict lingering symptoms.

CONCLUSION: Long-COVID and post-COVID are also common in outpatients. In 32%, it takes more than 12 weeks to return to usual health.}, } @article {pmid36654638, year = {2022}, author = {Kintrilis, N and Gkinos, CP and Galinos, I}, title = {Prolonged COVID-19 in a Multiple Sclerosis Patient Treated With Rituximab.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32523}, pmid = {36654638}, issn = {2168-8184}, abstract = {Immunocompromised patients commonly present prolonged viral shedding of the novel coronavirus SARS-CoV-2, detected through reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal or oropharyngeal swabs. The detection and estimation of the viral load in patients with COVID-19 is of utmost importance, not only for the effective isolation of the patient but also from a therapeutic point of view. In the current study, we present the case of an immunocompromised patient receiving rituximab infusions for the treatment of multiple sclerosis who exhibited COVID-19 clinical symptomatology for an extended period of time along with prolonged viral shedding while at the same time being unable to organize sufficient humoral immunity. Despite being fully vaccinated and having suffered symptomatic SARS-CoV-2 infections, antibodies against the virus remained undetected. Clinical relapse of his symptoms led to the trialing of a multitude of therapeutic interventions in order to combat the disease, with an extended remdesivir regimen proving the most efficacious in the alleviation of his symptoms. This case demonstrates how immunocompromised COVID-19 patients should be regarded under a different scope when it comes to the diagnosis, management, and resolution of their SARS-CoV-2 infection.}, } @article {pmid36653613, year = {2023}, author = {Graham, F}, title = {Daily briefing: At least 65 million people have long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-023-00114-0}, pmid = {36653613}, issn = {1476-4687}, } @article {pmid36652991, year = {2023}, author = {Wan, EYF and Mathur, S and Zhang, R and Yan, VKC and Lai, FTT and Chui, CSL and Li, X and Wong, CKH and Chan, EWY and Yiu, KH and Wong, ICK}, title = {Association of COVID-19 with short- and long-term risk of cardiovascular disease and mortality: a prospective cohort in UK Biobank.}, journal = {Cardiovascular research}, volume = {119}, number = {8}, pages = {1718-1727}, doi = {10.1093/cvr/cvac195}, pmid = {36652991}, issn = {1755-3245}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Child, Preschool ; *Cardiovascular Diseases/diagnosis/epidemiology/etiology ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Biological Specimen Banks ; Risk Factors ; *COVID-19/diagnosis/complications ; United Kingdom/epidemiology ; }, abstract = {AIMS: This study aims to evaluate the short- and long-term associations between COVID-19 and development of cardiovascular disease (CVD) outcomes and mortality in the general population.

METHODS AND RESULTS: A prospective cohort of patients with COVID-19 infection between 16 March 2020 and 30 November 2020 was identified from UK Biobank, and followed for up to 18 months, until 31 August 2021. Based on age (within 5 years) and sex, each case was randomly matched with up to 10 participants without COVID-19 infection from two cohorts-a contemporary cohort between 16 March 2020 and 30 November 2020 and a historical cohort between 16 March 2018 and 30 November 2018. The characteristics between groups were further adjusted with propensity score-based marginal mean weighting through stratification. To determine the association of COVID-19 with CVD and mortality within 21 days of diagnosis (acute phase) and after this period (post-acute phase), Cox regression was employed. In the acute phase, patients with COVID-19 (n = 7584) were associated with a significantly higher short-term risk of CVD {hazard ratio (HR): 4.3 [95% confidence interval (CI): 2.6- 6.9]; HR: 5.0 (95% CI: 3.0-8.1)} and all-cause mortality [HR: 81.1 (95% CI: 58.5-112.4); HR: 67.5 (95% CI: 49.9-91.1)] than the contemporary (n = 75 790) and historical controls (n = 75 774), respectively. Regarding the post-acute phase, patients with COVID-19 (n = 7139) persisted with a significantly higher risk of CVD in the long-term [HR: 1.4 (95% CI: 1.2-1.8); HR: 1.3 (95% CI: 1.1- 1.6)] and all-cause mortality [HR: 5.0 (95% CI: 4.3-5.8); HR: 4.5 (95% CI: 3.9-5.2) compared to the contemporary (n = 71 296) and historical controls (n = 71 314), respectively.

CONCLUSIONS: COVID-19 infection, including long-COVID, is associated with increased short- and long-term risks of CVD and mortality. Ongoing monitoring of signs and symptoms of developing these cardiovascular complications post diagnosis and up till at least a year post recovery may benefit infected patients, especially those with severe disease.}, } @article {pmid36652923, year = {2024}, author = {Zanini, G and Selleri, V and Roncati, L and Coppi, F and Nasi, M and Farinetti, A and Manenti, A and Pinti, M and Mattioli, AV}, title = {Vascular "Long COVID": A New Vessel Disease?.}, journal = {Angiology}, volume = {75}, number = {1}, pages = {8-14}, pmid = {36652923}, issn = {1940-1574}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Microcirculation ; Blood Platelets ; }, abstract = {Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as "Long Covid (LC)" disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first "endotheliitis," is often followed by production of "Neutrophil Extracellular Trap," and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis. In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible "LC" disease.}, } @article {pmid36652836, year = {2023}, author = {Tripathy, S and Kar, SK}, title = {Comments on "Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge".}, journal = {Asian journal of psychiatry}, volume = {82}, number = {}, pages = {103455}, pmid = {36652836}, issn = {1876-2026}, mesh = {Humans ; *COVID-19 ; Patient Discharge ; *Cognitive Dysfunction/etiology ; *Cognition Disorders ; Survivors/psychology ; }, } @article {pmid36651103, year = {2023}, author = {Bussani, R and Zentilin, L and Correa, R and Colliva, A and Silvestri, F and Zacchigna, S and Collesi, C and Giacca, M}, title = {Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19.}, journal = {The Journal of pathology}, volume = {259}, number = {3}, pages = {254-263}, pmid = {36651103}, issn = {1096-9896}, support = {787971/ERC_/European Research Council/International ; RG/19/11/34633/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; RNA, Viral/genetics ; Endothelial Cells ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11-300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.}, } @article {pmid36649958, year = {2023}, author = {Quinn, KL and Razak, F and Cheung, AM}, title = {Assessing common and potentially modifiable symptoms of post-COVID-19 condition (long COVID) in adults.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {2}, pages = {E76-E77}, pmid = {36649958}, issn = {1488-2329}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36649955, year = {2023}, author = {Quinn, KL and Razak, F and Cheung, AM}, title = {Diagnosing post-COVID-19 condition (long COVID) in adults.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {2}, pages = {E78-E79}, pmid = {36649955}, issn = {1488-2329}, mesh = {Humans ; Adult ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; COVID-19 Testing ; }, } @article {pmid36649954, year = {2023}, author = {Saigle, V}, title = {"My family doctor didn't know how to help me": a teenager's perspective on being diagnosed with long COVID.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {2}, pages = {E84}, doi = {10.1503/cmaj.221846}, pmid = {36649954}, issn = {1488-2329}, mesh = {Humans ; Adolescent ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36649950, year = {2023}, author = {Saigle, V}, title = {A patient's perspective on long COVID: improvement month to month not week to week.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {2}, pages = {E83}, doi = {10.1503/cmaj.221816}, pmid = {36649950}, issn = {1488-2329}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36649947, year = {2023}, author = {Quinn, KL and Cheung, AM and Razak, F}, title = {Treating common and potentially modifiable symptoms of post-COVID-19 condition (long COVID) in adults.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {195}, number = {2}, pages = {E80-E81}, pmid = {36649947}, issn = {1488-2329}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36649730, year = {2023}, author = {Rutsch, M and Frommhold, J and Buhr-Schinner, H and Gross, T and Schüller, PO and Deck, R}, title = {[Pneumological Rehabilitation in Patients with Long Covid - Health Changes at the End of the Inpatient Rehabilitation Measure].}, journal = {Die Rehabilitation}, volume = {62}, number = {6}, pages = {359-368}, doi = {10.1055/a-1964-7401}, pmid = {36649730}, issn = {1439-1309}, mesh = {Humans ; Treatment Outcome ; *Inpatients ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Prospective Studies ; *COVID-19 ; Germany/epidemiology ; }, abstract = {BACKGROUND: Some people suffering from Covid-19 can be affected by persistent symptoms and long-term consequences of the disease (Long Covid) beyond their acute phase. Consequently, this can lead to restrictions in participation. Therefore, the focus is on medical rehabilitation in which Long Covid is treated as a new challenge.

METHODS: A prospective, exploratory observational study will be conducted. The written survey of Long Covid rehabilitants takes place at the beginning and end of the pneumological rehabilitation. The aim of the study is to describe the rehabilitation contents and goals, the subjective burdens, the social and occupational participation as well as the health-related changes. Among other factors, disease-specific symptoms, quality of life, participation, psychological impairments, fatigue, and performance were recorded.

RESULTS: Long Covid rehabilitants (N=221) participate in the written survey. At the end of rehabilitation, the questionnaire survey indicated significant improvements in almost all outcome parameters with a large effect (p<0.01; ES between 0.76 (anxiety) and 1.30 (fatigue)). All corona symptoms, such as breathlessness on exertion, fatigue or lack of strength improved significantly at the end of rehabilitation. Moreover, the rehabilitants most frequently name the improvement of their health (92%), the increase of their performance (92%) and the improvement of the respiratory muscle strength (78%) as rehabilitation goals. In fact, these goals are achieved by 60 to 70%, significantly fewer rehabilitation patients reach the restoration of their ability to work (32%) or a better ability to concentrate (17%). Respiratory physiotherapy, endurance training and medical training therapy are described as most helpful. At the end of rehabilitation, 76% rated their rehabilitation success as good to excellent based on a single question.

CONCLUSION: The first data of the study reveal that Long Covid rehabilitants are exposed to substantial burdens. Through medical rehabilitation, the patients experience medical and social support and experience significant improvements in all recorded health-related outcomes.}, } @article {pmid36648965, year = {2022}, author = {Jason, LA and Dorri, JA}, title = {ME/CFS and Post-Exertional Malaise among Patients with Long COVID.}, journal = {Neurology international}, volume = {15}, number = {1}, pages = {1-11}, pmid = {36648965}, issn = {2035-8385}, support = {R01 NS111105/NS/NINDS NIH HHS/United States ; R01NS111105/NS/NINDS NIH HHS/United States ; }, abstract = {This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise. The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 71% met criteria for ME/CFS and of those who did not report they had ME/CFS, 40% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.}, } @article {pmid36648915, year = {2023}, author = {Okoye, C and Franchi, R and Calabrese, AM and Morelli, V and Peta, U and Mazzarone, T and Pompilii, IM and Coppini, G and Rogani, S and Calsolaro, V and Monzani, F}, title = {Determinants of 1-Year Adverse Event Requiring Re-Hospitalization in COVID-19 Oldest Old Survivors.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {8}, number = {1}, pages = {}, pmid = {36648915}, issn = {2308-3417}, abstract = {The incidence of "Long COVID" syndrome appears to be increasing, particularly in the geriatric population. At present, there are few data regarding the relationship between long COVID and the risk of re-hospitalization in the oldest old survivors. Patients older than 80 years consecutively hospitalized for COVID-19 in our tertiary care hospital were enrolled and followed after discharge in a 12-month ambulatory program. A comprehensive geriatric assessment (CGA), including functional capabilities and physical and cognitive performances, was performed at 6-month follow-up. Frailty degree was assessed using a 30-item frailty index. The re-hospitalization rate was assessed at 12-month follow-up through a computerized archive and phone interviews. Out of 100 patients discharged after hospitalization for COVID-19 (mean [SD] age 85 [4.0] years), 24 reported serious adverse events requiring re-hospitalization within 12 months. The most frequent causes of re-hospitalization were acute heart failure (HF), pneumonia and bone fracture (15.3% each). By multivariate logistic analysis, after adjustment for potential confounders, history of chronic HF [aOR: 3.00 (CI 95%: 1.10-8.16), p = 0.031] or chronic renal failure [aOR: 3.83 (CI 95%: 1.09-13.43), p = 0.036], the burden of comorbidity [(CIRSc) aOR: 1.95 (CI 95%: 1.28-2.97), p = 0.002] and frailty [aOR: 7.77 (CI 95%: 2.13-28.27), p = 0.002] resulted as independent predictors of re-hospitalization. One-fourth of the oldest old patients previously hospitalized for COVID-19 suffered from adverse events requiring re-hospitalization, two-thirds of them within three months after discharge. Frailty, the burden of comorbidity, history of chronic HF or chronic renal failure, but not COVID-19 disease severity, independently predicted re-hospitalization.}, } @article {pmid36648876, year = {2023}, author = {Vink, M and Vink-Niese, A}, title = {The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Diseases (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {36648876}, issn = {2079-9721}, abstract = {The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies. In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines. Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments. Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies. The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study. It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies. The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect. Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients. At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university. In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2.}, } @article {pmid36646091, year = {2023}, author = {Lutchmansingh, DD and Higuero Sevilla, JP and Possick, JD and Gulati, M}, title = {"Long Haulers".}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {1}, pages = {130-142}, doi = {10.1055/s-0042-1759568}, pmid = {36646091}, issn = {1098-9048}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Algorithms ; Disease Progression ; }, abstract = {Post-COVID conditions continue to afflict patients long after acute severe acute respiratory syndrome-coronavirus-2 (SARS CoV-2) infection. Over 50 symptoms across multiple organ systems have been reported, with pulmonary, cardiovascular, and neuropsychiatric sequelae occurring most frequently. Multiple terms have been used to describe post-COVID conditions including long COVID, long-haul COVID, postacute coronavirus disease 2019 (COVID-19), postacute sequelae of SARS-CoV-2 infection, long-term effects of COVID, and chronic COVID-19; however, standardized assessments and treatment algorithms for patients have generally been lacking. This review discusses the epidemiology and risk factors for post-COVID conditions and provides a general overview of the diagnostic assessment and treatment of specific manifestations. Data derived from the multitude of observational studies and scientific investigations into pathogenesis are providing a clearer understanding of the distinct phenotypes of post-COVID conditions. Insight gained from these studies and ongoing interventional trials continues to lead to the development of clinical protocols directed toward improving COVID-19 survivors' quality of life and preventing or reducing long-term morbidity.}, } @article {pmid36646086, year = {2023}, author = {Habet, V and Oliveira, CR}, title = {Clinical Epidemiology of Pediatric Coronavirus Disease 2019 and its Postacute Sequelae.}, journal = {Seminars in respiratory and critical care medicine}, volume = {44}, number = {1}, pages = {66-74}, pmid = {36646086}, issn = {1098-9048}, support = {K23 AI159518/AI/NIAID NIH HHS/United States ; L40 AI120154/AI/NIAID NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Quality of Life ; Disease Progression ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; *COVID-19/epidemiology/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has affected individuals of all ages across. Although children generally experience a benign illness from COVID-19, the emergence of novel variants of the virus has resulted in significant changes in the morbidity and mortality rates for this age group. Currently, COVID-19 is the eighth leading cause of pediatric deaths in the United States. In addition to acute respiratory illness, some children can develop a severe postinfectious condition known as a multisystem inflammatory syndrome in children, which can progress to rapid-onset cardiogenic shock. Recovery from COVID-19 can also be slow for some children, resulting in persistent or reoccurring symptoms for months, commonly referred to as long COVID. These postinfectious sequelae are often distressing for children and their parents, can negatively impact the quality of life, and impose a considerable burden on the health care system. In this article, we review the clinical epidemiology of pediatric COVID-19 and outline the management considerations for its acute and postacute manifestations.}, } @article {pmid36645453, year = {2023}, author = {Wong, MC and Huang, J and Wong, YY and Wong, GL and Yip, TC and Chan, RN and Chau, SW and Ng, SC and Wing, YK and Chan, FK}, title = {Epidemiology, Symptomatology, and Risk Factors for Long COVID Symptoms: Population-Based, Multicenter Study.}, journal = {JMIR public health and surveillance}, volume = {9}, number = {}, pages = {e42315}, pmid = {36645453}, issn = {2369-2960}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; China/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: Long COVID induces a substantial global burden of disease. The pathogenesis, complications, and epidemiological and clinical characteristics of patients with COVID-19 in the acute phase have been evaluated, while few studies have characterized the epidemiology, symptomatology, and risk factors of long COVID symptoms. Its characteristics among patients with COVID-19 in the general population remain unaddressed.

OBJECTIVE: We examined the prevalence of long COVID symptoms, its symptom patterns, and its risk factors in 4 major Chinese cities in order to fill the knowledge gap.

METHODS: We performed a population-based, multicenter survey using a representative sampling strategy via the Qualtrics platform in Beijing, Shanghai, Guangzhou, and Hong Kong in June 2022. We included 2712 community-dwelling patients with COVID-19 and measured the prevalence of long COVID symptoms defined by the World Health Organization (WHO), and their risk factors. The primary outcomes were the symptoms of long COVID, with various levels of impact. A descriptive analysis of the prevalence and distribution of long COVID symptoms according to disease severity was conducted. A sensitivity analysis of increasing the number of long COVID symptoms was also conducted. Univariate and multivariate regression analyses were performed to examine the risk factors of severe long COVID symptoms, including age, gender, marital status, current occupation, educational level, living status, smoking habits, monthly household income, self-perceived health status, the presence of chronic diseases, the use of chronic medication, COVID-19 vaccination status, and the severity of COVID-19.

RESULTS: The response rate was 63.6% (n=2712). The prevalence of long COVID, moderate or severe long COVID, and severe long COVID was 90.4% (n=2452), 62.4% (n=1692), and 31.0% (n=841), respectively. Fatigue (n=914, 33.7%), cough (n=865, 31.9%), sore throat (n=841, 31.0%), difficulty in concentrating (n=828, 30.5%), feeling of anxiety (n=817, 30.2%), myalgia (n=811, 29.9%), and arthralgia (n=811, 29.9%) were the most common severe long COVID symptoms. From multivariate regression analysis, female gender (adjusted odds ratio [aOR]=1.49, 95% CI 1.13-1.95); engagement in transportation, logistics, or the discipline workforce (aOR=2.52, 95% CI 1.58-4.03); living with domestic workers (aOR=2.37, 95% CI 1.39-4.03); smoking (aOR=1.55, 95% CI 1.17-2.05); poor or very poor self-perceived health status (aOR=15.4, 95% CI 7.88-30.00); ≥3 chronic diseases (aOR=2.71, 95% CI 1.54-4.79); chronic medication use (aOR=4.38, 95% CI 1.66-11.53); and critical severity of COVID-19 (aOR=1.52, 95% CI 1.07-2.15) were associated with severe long COVID. Prior vaccination with ≥2 doses of COVID-19 vaccines was a protective factor (aOR=0.35-0.22, 95% CI 0.08-0.90).

CONCLUSIONS: We examined the prevalence of long COVID symptoms in 4 Chinese cities according to the severity of COVID-19. We also evaluated the pattern of long COVID symptoms and their risk factors. These findings may inform early identification of patients with COVID-19 at risk of long COVID and planning of rehabilitative services.}, } @article {pmid36643576, year = {2023}, author = {Goodman, ML and Molldrem, S and Elliott, A and Robertson, D and Keiser, P}, title = {Long COVID and mental health correlates: a new chronic condition fits existing patterns.}, journal = {Health psychology and behavioral medicine}, volume = {11}, number = {1}, pages = {2164498}, pmid = {36643576}, issn = {2164-2850}, abstract = {BACKGROUND: Emerging Long COVID research indicates the condition has major population health consequence. Other chronic conditions have previously been associated with functional and mental health challenges - including depression, anxiety, post-traumatic stress disorder (PTSD), suicide ideation, substance use and lower life satisfaction.

METHODS: This study explores correlations between self-reported Long COVID, functional and mental health challenges among a random community-based sample of people (n = 655) aged 20-50 years who contracted COVID-19 prior to vaccination in a Texas county. A random sample of eligible participants was mailed a link to participate in a semi-structured questionnaire. Participant responses, including open-ended responses regarding their experience following COVID-19, were paired with health system data.

RESULTS: Long COVID was associated with increased presence of depression (13% increase), anxiety (28% increase), suicide ideation (10% increase), PTSD (20% increase), and decreased life satisfaction and daily functioning. Structural equation modeling, controlling for sociodemographic variables and imposing a theoretical framework from existing chronic disease research, demonstrated correlations between Long COVID and higher PTSD, suicide ideation and lower life satisfaction were mediated by higher daily functional challenges and common mental disorders.

CONCLUSIONS: Basic and applied, interdisciplinary research is urgently needed to characterize the population-based response to the new challenge of Long COVID.}, } @article {pmid36643174, year = {2023}, author = {Arifin, Y and Gunawan, EP and Ohyver, M}, title = {Developing an online information portal for enhancing society awareness of RPTRA (A case study RPTRA MAYA ASRI 13).}, journal = {Procedia computer science}, volume = {216}, number = {}, pages = {144-150}, pmid = {36643174}, issn = {1877-0509}, abstract = {The long COVID-19 pandemic has limited the activities of Ruang Publik Terpadu Ramah Anak (RPTRA) such as environment cleaning, repair of RPTRA infrastructure, learning and others, as well as the lack of public awareness about the existence and importance of RPTRA to the public and foreign tourists encouraging the RPTRA to make changes in the dissemination of information about the activities carried out in the RPTRA through the use of technology to survive and grow even during the Covid-19 Pandemic. The methodology used in this research is Group Discussion Forum with the administrators of the RPTRA Maya ASRI 13 to learn about the needs and expectations of the RPTRA administrators regarding the web portal to be built. Then, the implementation of the conceptual model, development, and evaluation of the effectiveness of the RPTRA information web portal was carried out. The contribution in this research is to implement a conceptual model on the information portal built on the platform of the Website with the PHP framework, which is then evaluated on the results of the pre-test and post-test about RPTRA the Wilcoxon-Signed Rank Test to test the effectiveness of the information web portal for general users. The results obtained from these tests indicate that the RPTRA Information Web Portal can help the public learn more about the existence of RPTRA Maya Asri 13.}, } @article {pmid36642294, year = {2023}, author = {Bourgonje, AR and Otten, AT}, title = {The Risk of Developing Long COVID in Patients With Inflammatory Bowel Diseases: Do Immunosuppressive Drugs Matter?.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {21}, number = {7}, pages = {1971-1972}, doi = {10.1016/j.cgh.2022.12.030}, pmid = {36642294}, issn = {1542-7714}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Immunosuppressive Agents/adverse effects ; *Inflammatory Bowel Diseases/complications/drug therapy/chemically induced ; }, } @article {pmid36642173, year = {2023}, author = {Fawzy, NA and Abou Shaar, B and Taha, RM and Arabi, TZ and Sabbah, BN and Alkodaymi, MS and Omrani, OA and Makhzoum, T and Almahfoudh, NE and Al-Hammad, QA and Hejazi, W and Obeidat, Y and Osman, N and Al-Kattan, KM and Berbari, EF and Tleyjeh, IM}, title = {A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {5}, pages = {570-577}, pmid = {36642173}, issn = {1469-0691}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Transcranial Direct Current Stimulation ; World Health Organization ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome.

OBJECTIVES: To systematically review registered trials currently investigating therapeutic modalities for PACS.

DATA SOURCES: A search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform.

Interventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.

METHODS: Data on trial characteristics and intervention characteristics were collected and summarized.

RESULTS: After screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed.

CONCLUSION: We identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.}, } @article {pmid36639608, year = {2023}, author = {Davis, HE and McCorkell, L and Vogel, JM and Topol, EJ}, title = {Long COVID: major findings, mechanisms and recommendations.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {3}, pages = {133-146}, pmid = {36639608}, issn = {1740-1534}, support = {UL1 TR002550/TR/NCATS NIH HHS/United States ; }, mesh = {Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *Biomedical Research ; }, abstract = {Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.}, } @article {pmid36639563, year = {2023}, author = {}, title = {Machine learning identifies long COVID patterns from electronic health records.}, journal = {Nature medicine}, volume = {29}, number = {1}, pages = {47-48}, pmid = {36639563}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Electronic Health Records ; Machine Learning ; SARS-CoV-2 ; }, abstract = {A machine learning algorithm identifies four reproducible clinical subphenotypes of long COVID from the electronic health records of patients with post-acute sequelae of SARS-CoV-2 infection within 30–180 days of infection; these patterns have implications for the treatment and management of long COVID.}, } @article {pmid36636846, year = {2023}, author = {Demirbuğa, A and Hançerli Törün, S and Kaba, Ö and Dede, E and Mete Atasever, N and Eryılmaz, CC and Okay, NS and Somer, A}, title = {[Long COVID in Children: A Pediatric Center Experience].}, journal = {Mikrobiyoloji bulteni}, volume = {57}, number = {1}, pages = {60-70}, doi = {10.5578/mb.20239905}, pmid = {36636846}, issn = {0374-9096}, mesh = {Adult ; Humans ; Male ; Child ; Female ; Adolescent ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Diabetes Mellitus, Type 2 ; Cough/epidemiology/etiology ; Fatigue/epidemiology/etiology ; }, abstract = {Although COVID-19 (Coronavirus disease-2019) is observed to be milder in children, it has been observed that the symptoms continue for a long time in many people after the acute period of the disease, especially the multisystemic inflammatory syndrome (MISC) that developed after COVID-19 with the progression of the pandemic. Although it was first defined by different names such as long COVID and post COVID in adults, it has been observed in studies that similar complaints such as cough, fatigue and difficulty in concentrating continue for a long time in children, just as in adults. In our study, we aimed to evaluate the status of long COVID in childhood. Our study included patients aged from one month to 18 years with moderate and severe symptoms who were hospitalized and discharged for SARS-CoV-2 infection in İstanbul University Faculty of Medicine between November 1, 2020 and November 1, 2021. A questionnaire form was created to learn about the complaints of the patients and their ongoing complaints. The patients/parents were called by phone and their complaints were recorded in the questionnaire. The patients were classified according to the definitions in the guidelines published by NICE, RCGP and SIGN. In total, 116 patients were included; 57.8% (n= 64) male, 42.5% (n= 49) female; 53.4% (n= 62) 0-9, 46.6% (n= 54) 10-18 years old. Comorbid conditions were found in 64 (55.2%) patients. The mean follow-up period was 5.90 ± 3.61 [min-max (1-12)] months; longest symptom durations: decrease in effort loss/fatigue 19.25 ± 74.56 (0-365) days, concentration difficulties 11.12 ± 49.75 (0-365) days, fatigue 9.61 ± 34.96 (0-365) days and cough were 8.34 ± 35.37 (0-365) days. The percentage of the patients who met the definition of subacute/ongoing symptomatic COVID-19 was 37.9% (n= 44). The most common symptoms were the decrease of effort capacity/fatigue 12.1% (n= 14) and the concentration difficulties 10.3% (n= 12) in subacute symptomatic patients. The percentage of patients matching the definition of chronic/post COVID-19 was 11.2% (n= 13). In the first year of the disease, ongoing complaints such as fatigue and concentration difficulties were observed in eight patients. The rate of concentration difficulties in the 10-18 age group was statistically significantly higher than the 0-9 age group (p= 0.037). In terms of other symptoms, no significant difference was found according to age, gender and concomitant disease status. Out of these, one patient was diagnosed with Type 2 diabetes mellitus during the acute illness, and two patients were diagnosed with allergic rhinitis after COVID-19. A statistically significant difference was found in the rates of concentration disorders according to age groups with subacute/ongoing symptoms. Although only the hospitalized patients were included, fatigue and difficulty in concentration were among the most common ongoing symptoms in our study, similar to the literature, and they were seen to be more common in older children. It is important both for early diagnosis and awareness to follow up children with COVID-19 in terms of symptoms, not only in terms of prolonged symptoms but also in terms of new diseases.}, } @article {pmid36636645, year = {2022}, author = {Dal Negro, RW and Turco, P and Povero, M}, title = {Nebivolol: an effective option against long-lasting dyspnoea following COVID-19 pneumonia - a pivotal double-blind, cross-over controlled study.}, journal = {Multidisciplinary respiratory medicine}, volume = {17}, number = {}, pages = {886}, pmid = {36636645}, issn = {1828-695X}, abstract = {BACKGROUND: Pulmonary microvascular occlusions can aggravate SARS-CoV-2 pneumonia and result in a variable decrease in capillary blood volume (Vc). Dyspnoea may persist for several weeks after hospital discharge in many patients who have "radiologically recovered" from COVID-19 pneumonia. Dyspnoea is frequently "unexplained" in these cases because abnormalities in lung vasculature are understudied. Furthermore, even when they are identified, therapeutic options are still lacking in clinical practice, with nitric oxide (NO) supplementation being used only for severe respiratory failure in the hospital setting. Nebivolol is the only selective β[1] adrenoceptor antagonist capable of inducing nitric oxide-mediated vasodilation by stimulating endothelial NO synthase via β3 agonism. The purpose of this study was to compare the effect of nebivolol versus placebo in patients who had low Vc and complained of dyspnoea for several weeks after COVID-19 pneumonia.

METHODS: Patients of both genders, aged ≥18 years, non-smokers, who had a CT scan that revealed no COVID-related parenchymal lesions but still complaining of dyspnoea 12-16 weeks after hospital discharge, were recruited. Spirometrical volumes, blood haemoglobin, SpO2, simultaneous diffusing capacity for carbon monoxide (CO) and NO (DLCO and DLNO, respectively), DLNO/DLCO ratio, Vc and exhaled NO (eNO) were measured together with their dyspnoea score (DS), heart frequency (HF), and blood arterial pressure (BAP). Data were collected before and one week after both placebo (P) and nebivolol (N) (2.5 mg od) double-blind cross-over administered at a two-week interval. Data were statistically compared, and p<0.05 assumed as statistically significant.

RESULTS: Eight patients (3 males) were investigated. In baseline, their mean DS was 2.5±0.6 SD, despite the normality of lung volumes. DLCO and DLNO mean values were lower than predicted, while mean DLNO/DLCO ratio was higher. Mean Vc proved substantially reduced. Placebo did not modify any variable (all p=ns) while N improved DLco and Vc significantly (+8.5%, p<0.04 and +17.7%, p<0.003, respectively). eNO also was significantly increased (+17.6%, p<0.002). Only N lowered the dyspnoea score (-76%, p<0.001). Systolic and diastolic BAP were slightly lowered (-7.5%, p<0.02 and -5.1%, p<0.04, respectively), together with HF (-16.8%, p<0.03).

CONCLUSIONS: The simultaneous assessment of DLNO, DLCO, DLNO/DLCO ratio, and Vc confirmed that long-lasting dyspnoea is related to hidden abnormalities in the lung capillary vasculature. These abnormalities can persist even after the complete resolution of parenchymal lesions regardless of the normality of lung volumes. Nebivolol, but not placebo, improves DS and Vc significantly. The mechanism suggested is the NO-mediated vasodilation via the β3 adrenoceptor stimulation of endothelial NO synthase. This hypothesis is supported by the substantial increase of eNO only assessed after nebivolol. As the nebivolol tolerability in these post-COVID normotensive patients was very good, the therapeutic use of nebivolol against residual and symptomatic signs of long-COVID can be suggested in out-patients.}, } @article {pmid36636391, year = {2023}, author = {Mattioli, AV and Coppi, F and Nasi, M and Pinti, M and Gallina, S}, title = {Long COVID: A New Challenge for Prevention of Obesity in Women.}, journal = {American journal of lifestyle medicine}, volume = {17}, number = {1}, pages = {164-168}, pmid = {36636391}, issn = {1559-8284}, abstract = {The long COVID affects individuals that do not recover for several weeks or months following the onset of symptoms of COVID-19. Obesity could play a role in the long COVID syndrome. During the pandemic, various factors contributed greatly to aggravating obesity in women leading to a pro-inflammatory and prothrombotic status. The present commentary explores the relationship between long COVID and obesity in women.}, } @article {pmid36634924, year = {2023}, author = {Sin, DD}, title = {Is long COVID an autoimmune disease?.}, journal = {The European respiratory journal}, volume = {61}, number = {1}, pages = {}, doi = {10.1183/13993003.02272-2022}, pmid = {36634924}, issn = {1399-3003}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Autoantibodies ; *COVID-19 ; *Autoimmune Diseases/complications/epidemiology ; }, } @article {pmid36633476, year = {2023}, author = {Aby, ES and Moafa, G and Latt, N and Sultan, MT and Cacioppo, PA and Kumar, S and Chung, RT and Bloom, PP and Gustafson, J and Daidone, M and Reinus, Z and Debes, JD and Sandhu, S and Sohal, A and Khalid, S and Roytman, M and Catana, AM and Wegermann, K and Carr, RM and Saiman, Y and Kassab, I and Chen, VL and Rabiee, A and Rosenberg, C and Nguyen, V and Gainey, C and Zhou, K and Chavin, K and Lizaola-Mayo, BC and Chascsa, DM and Varelas, L and Moghe, A and Dhanasekaran, R}, title = {Long-term clinical outcomes of patients with COVID-19 and chronic liver disease: US multicenter COLD study.}, journal = {Hepatology communications}, volume = {7}, number = {1}, pages = {e8874}, pmid = {36633476}, issn = {2471-254X}, mesh = {Adult ; Humans ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; *Liver Diseases ; Hospitalization ; }, abstract = {BACKGROUND: COVID-19 is associated with higher morbidity and mortality in patients with chronic liver diseases (CLDs). However, our understanding of the long-term outcomes of COVID-19 in patients with CLD is limited.

METHODS: We conducted a multicenter, observational cohort study of adult patients with CLD who were diagnosed with COVID-19 before May 30, 2020, to determine long-term clinical outcomes. We used a control group of patients with CLD confirmed negative for COVID-19.

RESULTS: We followed 666 patients with CLD (median age 58 years, 52.8% male) for a median of 384 (interquartile range: 31-462) days. The long-term mortality was 8.1%; with 3.6% experiencing delayed COVID-19-related mortality. Compared to a propensity-matched control group of patients with CLD without COVID-19 (n=1332), patients with CLD with COVID-19 had worse long-term survival [p<0.001; hazards ratio (HR): 1.69; 95% CI: 1.19-2.41] and higher rate of hospitalization (p<0.001, HR: 2.00, 1.62-2.48) over a 1-year follow-up period. Overall, 29.9% of patients reported symptoms of long-COVID-19. On multivariable analysis, female sex (p=0.05, HR: 2.45, 1.01-2.11), Hispanic ethnicity (p=0.003, HR: 1.94, 1.26-2.99), and severe COVID-19 requiring mechanical ventilation (p=0.028, HR: 1.74, 1.06-2.86) predicted long-COVID-19. In survivors, liver-related laboratory parameters showed significant improvement after COVID-19 resolution. COVID-19 vaccine status was available for 72% (n=470) of patients with CLD and history of COVID-19, of whom, 70% (n=326) had received the COVID-19 vaccine.

CONCLUSIONS: Our large, longitudinal, multicenter study demonstrates a high burden of long-term mortality and morbidity in patients with CLD and COVID-19. Symptoms consistent with long-COVID-19 were present in 30% of patients with CLD. These results illustrate the prolonged implications of COVID-19 both for recovering patients and for health care systems.}, } @article {pmid36633452, year = {2023}, author = {Hallek, M and Adorjan, K and Behrends, U and Ertl, G and Suttorp, N and Lehmann, C}, title = {Post-COVID Syndrome.}, journal = {Deutsches Arzteblatt international}, volume = {120}, number = {4}, pages = {48-55}, pmid = {36633452}, issn = {1866-0452}, mesh = {Adult ; Adolescent ; Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Inflammation ; Pandemics/prevention & control ; Vaccination ; }, abstract = {BACKGROUND: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).

METHODS: The data presented here were derived from a systematic literature review.

RESULTS: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.

CONCLUSION: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.}, } @article {pmid36632532, year = {2023}, author = {Rowe, K}, title = {Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Adolescents: Practical Guidance and Management Challenges.}, journal = {Adolescent health, medicine and therapeutics}, volume = {14}, number = {}, pages = {13-26}, pmid = {36632532}, issn = {1179-318X}, abstract = {This paper reviews the current understanding of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and whether any treatment strategies have been effective. ME/CFS is a condition of as yet unknown etiology that commonly follows an infective process. It includes a new onset of fatigue (of more than 3-6 month duration and not relieved by rest), post-exertional malaise, cognitive difficulties and unrefreshing sleep, and frequently orthostatic intolerance, somatic symptoms and pain. Long COVID has renewed interest in the condition and stimulated research with findings suggestive of a multisystem neuroimmune disease. There are no definitively effective treatments. Despite earlier recommendations regarding graded exercise therapy and cognitive behavior therapy, the current recommendations are managing symptoms, with lifestyle management and supportive care. This paper provides an outline of strategies that young people and their families have reported as helpful in managing a chronic illness that impacts their life socially, physically, emotionally, cognitively and educationally. As the illness frequently occurs at a time of rapid developmental changes, reducing these impacts is reported to be as important as managing the physical symptoms. Young people face a mean duration of 5 years illness (range 1-16 years) with a likely residual 20% having significant restrictions after 10 years. Their feedback has suggested that symptom management, self-management strategies, advocacy and educational liaison have been the most helpful. They value professionals who will listen and take them seriously, and after excluding alternative diagnoses, they explain the diagnosis, are supportive and assist in monitoring their progress. Remaining engaged in education was the best predictor of later functioning. This allowed for social connections, as well as potential independence and fulfilling some aspirations. The need to consider the impact of this chronic illness on all aspects of adolescent development, as part of management, is highlighted.}, } @article {pmid36632218, year = {2023}, author = {Huang, S and Zhou, X and Zhao, W and Du, Y and Yang, D and Huang, Y and Chen, Y and Zhang, H and Yang, G and Liu, J and Luo, H}, title = {Dynamic white matter changes in recovered COVID-19 patients: a two-year follow-up study.}, journal = {Theranostics}, volume = {13}, number = {2}, pages = {724-735}, pmid = {36632218}, issn = {1838-7640}, mesh = {Humans ; Follow-Up Studies ; *White Matter/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Brain/diagnostic imaging ; Inflammation ; }, abstract = {Background and purpose: Long COVID with regard to the neurological system deserves more attention, as a surge of treated patients are being discharged from the hospital. As the dynamic changes in white matter after two years remain unknown, this characteristic was the focus of this study. Methods: We investigated 17 recovered COVID-19 patients at two years after discharge. Diffusion tensor imaging, neurite orientation dispersion and density imaging were performed to identify white matter integrity and changes from one to two years after discharge. Data for 13 revisited healthy controls were collected as a reference. Subscales of the Wechsler Intelligence scale were used to assess cognitive function. Repeated-measures ANOVA was used to detect longitudinal changes in 17 recovered COVID-19 patients and 13 healthy controls after one-year follow-up. Correlations between diffusion metrics, cognitive function, and other clinical characteristics (i.e., inflammatory factors) were also analyzed. Results: Longitudinal analysis showed the recovery trends of large-scale brain regions, with small-scale brain region deterioration from one year to two years after SARS-CoV-2 infection. However, persistent white matter abnormalities were noted at two years after discharge. Longitudinal changes of cognitive function showed no group difference. But cross-sectional cognitive difference between recovered COVID-19 patients and revisited HCs was detected. Inflammation levels in the acute stage correlated positively with white matter abnormalities and negatively with cognitive function. Moreover, the more abnormal the white matter was at two years, the greater was the cognitive deficit present. Conclusion: Recovered COVID-19 patients showed longitudinal recovery trends of white matter. But also had persistent white matter abnormalities at two years after discharge. Inflammation levels in the acute stage may be considered predictors of cognition and white matter integrity, and the white matter microstructure acts as a biomarker of cognitive function in recovered COVID-19 patients. These findings provide an objective basis for early clinical intervention.}, } @article {pmid36631153, year = {2023}, author = {Mizrahi, B and Sudry, T and Flaks-Manov, N and Yehezkelli, Y and Kalkstein, N and Akiva, P and Ekka-Zohar, A and Ben David, SS and Lerner, U and Bivas-Benita, M and Greenfeld, S}, title = {Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.}, journal = {BMJ (Clinical research ed.)}, volume = {380}, number = {}, pages = {e072529}, pmid = {36631153}, issn = {1756-1833}, mesh = {Adult ; Child ; Humans ; Female ; Male ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Cohort Studies ; Retrospective Studies ; Dyspnea ; }, abstract = {OBJECTIVES: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status.

DESIGN: Retrospective nationwide cohort study.

SETTING: Electronic medical records from an Israeli nationwide healthcare organisation.

POPULATION: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.

MAIN OUTCOME MEASURES: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.

RESULTS: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.

CONCLUSIONS: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.}, } @article {pmid36631024, year = {2022}, author = {Soh, HS and Cho, B}, title = {Long COVID-19 and Health-Related Quality of Life of Mild Cases in Korea: 3-Months Follow-up of a Single Community Treatment Center.}, journal = {Journal of Korean medical science}, volume = {37}, number = {46}, pages = {e326}, pmid = {36631024}, issn = {1598-6357}, mesh = {Humans ; Female ; *Quality of Life/psychology ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; Prospective Studies ; Surveys and Questionnaires ; Republic of Korea/epidemiology ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) survivors mount as the pandemic continues. To date, studies on persistent symptoms and their effects on health-related quality of life (HRQoL) in mild COVID-19 cases have been limited.

METHODS: A prospective online survey was conducted in COVID-19 patients who were admitted to Seongnam Community Treatment Center, an isolation center in South Korea, from November 23rd 2021 to January 2nd 2022. Patients above the age of 19 with no or mild symptoms were included in the study. Total of 147 patients returned to the follow-up survey 3 months after discharge. Baseline demographics, clinical characteristics, symptoms, and EuroQol-5 dimensions-5 levels (EQ-5D-5L) measures were investigated.

RESULTS: The median (interquartile range [IQR]) interval period between the initial and follow-up survey was 96.0 (93.0-98.0) days. The median (IQR) age of participants was 51.0 (43.0-61.0). During isolation, 131 (89.1%) patients manifested symptoms. On follow-up, 82 (55.8%) participants remained symptomatic. Common symptoms were constitutional (fatigue, myalgia), neurological (memory impairment, hyposmia, hypogeusia, dizziness), and neuropsychiatric (anxiety) symptoms. Participants with remaining neuropsychiatric symptoms reported the lowest EQ-5D-5L index values. Factors associated with persistent symptoms and diminished HRQoL were identified as female sex, metabolic disease, and anxiety during acute COVID-19 phase.

CONCLUSIONS: Cardiopulmonary symptoms improved over time but constitutional, neurological, neuropsychiatric symptoms remained. Patients with neuropsychiatric symptoms (anxiety and insomnia) reported the worst HRQoL. Female sex, metabolic disease, and anxiety during the acute COVID-19 phase were associated with long COVID. Observations of long-term symptoms of COVID-19 with decline in HRQoL and integrated research in COVID-19 survivors are warranted.}, } @article {pmid36629074, year = {2024}, author = {Killingback, C and Thompson, M and Nettleton, M and Hyde, L and Marshall, P and Shepherdson, J and Crooks, MG and Green, A and Simpson, AJ}, title = {Telerehabilitation for patients who have been hospitalised with covid-19: a qualitative study.}, journal = {Disability and rehabilitation}, volume = {46}, number = {1}, pages = {150-158}, doi = {10.1080/09638288.2022.2159075}, pmid = {36629074}, issn = {1464-5165}, mesh = {Humans ; *Telerehabilitation/methods ; *COVID-19/epidemiology ; Exercise Therapy ; Qualitative Research ; Exercise ; }, abstract = {PURPOSE: The aim of this qualitative study was to explore the views of participants of a group-based, supervised, telerehabilitation programme, following discharge from hospital with Covid-19. This study was part of a single-centre, fast-track (wait-list), randomised, mixed-methods, feasibility trial of telerehabilitation (Registration: Clinicaltrials.gov reference:285205).

METHODS: Semi-structured interviews were conducted over a virtual teleconference platform with 10 participants who took part in a telerehabilitation programme following Covid-19 after discharge from an acute hospital. Data were transcribed verbatim and analysed using thematic analysis.

RESULTS: Five themes were important from the participant perspective: telerehabilitation programme as part of the Covid-19 journey; the telerehabilitation programme design and delivery; peer aspects; the role of the instructor; and the role of technology and online delivery.

CONCLUSIONS: Overall, the telerehabilitation programme was a positive experience for participants. The instructors were central to this positive view as was the group nature of the programme. The group aspect was particularly important in supporting the broader perceived wellbeing gains, such as the sense of enjoyment and reduced social isolation. Several participants would have liked to have continued with the exercises beyond the six-week intervention indicating that the programme could be a way to help people sustain a physically active lifestyle.IMPLICATIONS FOR REHABILITATIONParticipants who were recovering from Covid-19 following hospital admission perceived the telerehabilitation to be a positive experience overall.The group aspect of the telerehabilitation programme was important in supporting the broader perceived wellbeing gains such as the sense of enjoyment and reduced social isolation.Telerehabilitation programmes for Covid-19 may need to include pathways for participants to continue to engage in exercise beyond the time-limited six-week intervention to support ongoing self-management.}, } @article {pmid36628054, year = {2023}, author = {van Wijhe, M and Fogh, K and Ethelberg, S and Karmark Iversen, K and Nielsen, H and Østergaard, L and Andersen, B and Bundgaard, H and Jørgensen, CS and Scharff, BFS and Ellermann-Eriksen, S and Johansen, IS and Fomsgaard, A and Grove Krause, T and Wiese, L and Fischer, TK and Mølbak, K and Benfield, T and Folke, F and Lippert, F and Ostrowski, SR and Koch, A and Erikstrup, C and Vangsted, AM and Sørensen, AIV and Ullum, H and Skov, RL and Simonsen, L and Nielsen, SD}, title = {Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey.}, journal = {Open forum infectious diseases}, volume = {10}, number = {1}, pages = {ofac679}, pmid = {36628054}, issn = {2328-8957}, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection.

METHODS: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome.

RESULTS: In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0-7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5-14.6]) and smell (OR, 11.2 [95% CI, 9.1-13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID.

CONCLUSIONS: Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.}, } @article {pmid36628048, year = {2022}, author = {Khan, MH and Kirkpatrick, KP and Deng, Y and Shah, KB}, title = {Stellate Ganglion Block for Long COVID Symptom Management: A Case Report.}, journal = {Cureus}, volume = {14}, number = {12}, pages = {e32295}, pmid = {36628048}, issn = {2168-8184}, abstract = {Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms. .}, } @article {pmid36626183, year = {2023}, author = {Lippi, G and Sanchis-Gomar, F and Henry, BM}, title = {COVID-19 and its long-term sequelae: what do we know in 2023?.}, journal = {Polish archives of internal medicine}, volume = {133}, number = {4}, pages = {}, doi = {10.20452/pamw.16402}, pmid = {36626183}, issn = {1897-9483}, mesh = {Humans ; Female ; Male ; *COVID-19 ; COVID-19 Vaccines ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Disease Progression ; }, abstract = {Post‑viral syndrome is a well‑known medical condition characterized by different levels of physical, cognitive, and emotional impairment that may persist with fluctuating severity after recovering from an acute viral infection. Unsurprisingly, COVID‑19 may also be accompanied by medium- and long‑term clinical sequelae after recovering from a SARS‑CoV‑2 infection. Although many clinical definitions have been provided, "long‑COVID" can be defined as a condition occurring in patients with a history of SARS‑CoV‑2 infection, developing 3 months from the symptoms onset, persisting for at least 2 months, and not explained by alternative diagnoses. According to recent global analyses, the cumulative prevalence of long‑COVID seems to range between 9% and 63%, and is up to 6‑fold higher than that of similar postviral infection conditions. Long‑COVID primarily encompasses the presence of at least 1 symptom, such as fatigue, dyspnea, cognitive impairment / brain fog, postexertional malaise, memory issues, musculoskeletal pain / spasms, cough, sleep disturbances, tachycardia / palpitations, altered smell / taste perception, headache, chest pain, and depression. The most important demographic and clinical predictors to date are female sex, older age, cigarette smoking, pre‑existing medical conditions, lack of COVID‑19 vaccination, infection with pre‑Omicron SARS‑CoV‑2 variants, number of acute phase symptoms, viral load, severe / critical COVID‑19 illness, as well as invasive mechanical ventilation. Concerning the care for long‑COVID patients, the greatest challenge is the fact that this syndrome cannot be considered a single clinical entity, and thus it needs an integrated multidisciplinary management, specifically tailored to the type and severity of symptoms.}, } @article {pmid36625747, year = {2023}, author = {Jeong, YJ and Wi, YM and Park, H and Lee, JE and Kim, SH and Lee, KS}, title = {Current and Emerging Knowledge in COVID-19.}, journal = {Radiology}, volume = {306}, number = {2}, pages = {e222462}, pmid = {36625747}, issn = {1527-1315}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Tomography, X-Ray Computed ; }, abstract = {COVID-19 has emerged as a pandemic leading to a global public health crisis of unprecedented morbidity. A comprehensive insight into the imaging of COVID-19 has enabled early diagnosis, stratification of disease severity, and identification of potential sequelae. The evolution of COVID-19 can be divided into early infectious, pulmonary, and hyperinflammatory phases. Clinical features, imaging features, and management are different among the three phases. In the early stage, peripheral ground-glass opacities are predominant CT findings, and therapy directly targeting SARS-CoV-2 is effective. In the later stage, organizing pneumonia or diffuse alveolar damage pattern are predominant CT findings and anti-inflammatory therapies are more beneficial. The risk of severe disease or hospitalization is lower in breakthrough or Omicron variant infection compared with nonimmunized or Delta variant infections. The protection rates of the fourth dose of mRNA vaccination were 34% and 67% against overall infection and hospitalizations for severe illness, respectively. After acute COVID-19 pneumonia, most residual CT abnormalities gradually decreased in extent, but they may remain as linear or multifocal reticular or cystic lesions. Advanced insights into the pathophysiologic and imaging features of COVID-19 along with vaccine benefits have improved patient care, but emerging knowledge of post-COVID-19 condition, or long COVID, also presents radiology with new challenges.}, } @article {pmid36625181, year = {2023}, author = {Fleig, M and Müller, T and Antonini, VM and Riera, J and Belliato, M and Broman, LM and Fowles, JA and Belohlavek, J and Lorusso, R and Vercaemst, L and Jones, T and Roeleveld, PP and Di Nardo, M and Barrett, N and Swol, J}, title = {Extracorporeal life support provision in COVID-19 patients - An international EuroELSO 2022 update survey.}, journal = {Perfusion}, volume = {38}, number = {1_suppl}, pages = {13-23}, pmid = {36625181}, issn = {1477-111X}, mesh = {Adult ; Humans ; Child ; *COVID-19/epidemiology ; *Extracorporeal Membrane Oxygenation ; Post-Acute COVID-19 Syndrome ; Surveys and Questionnaires ; Pandemics ; }, abstract = {INTRODUCTION: An analysis on the ECLS use for patients with respiratory or cardiac support in COVID-19 based on an international response to EuroELSO survey, aims to generate a more comprehensive understanding of ECLS role during the recent viral pandemic.

METHODS: EuroELSO announced the survey at the 10th annual congress in London, May 2022. The survey covered 26 multiple-choice questions.

RESULTS: The survey returned 69 questionnaires from 62 centers across 22 European countries and seven centers across five non-European countries. Most of the centers providing ECLS for COVID-19 patients had more than 30 runs for respiratory support since December 2019. In the same period, at least 31 runs in adult COVID-19 patients have been performed in 48 of 69 centers (69.6%). The reported pediatric data from 18 centers is limited to less than the patients per center.

CONCLUSION: Majority of the COVID-19 patients received respiratory ECLS support and adult patients dominated. The indications and contraindications are broadly aligned with available guidelines. Most of the centers considered age >65 or biological age as a relative or absolute contraindication for ECLS in COVID-19. ECLS withdrawal criteria in COVID-19 are controversial because the long-term outcomes after ECLS in COVID-19 and the impact of critical illness and the impact of long-COVID are still not known.}, } @article {pmid36624784, year = {2022}, author = {The Lancet Regional Health-Europe, }, title = {Long COVID: An opportunity to focus on post-acute infection syndromes.}, journal = {The Lancet regional health. Europe}, volume = {22}, number = {}, pages = {100540}, doi = {10.1016/j.lanepe.2022.100540}, pmid = {36624784}, issn = {2666-7762}, } @article {pmid36623520, year = {2023}, author = {Xu, E and Xie, Y and Al-Aly, Z}, title = {Risks and burdens of incident dyslipidaemia in long COVID: a cohort study.}, journal = {The lancet. Diabetes & endocrinology}, volume = {11}, number = {2}, pages = {120-128}, pmid = {36623520}, issn = {2213-8595}, mesh = {United States/epidemiology ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cohort Studies ; SARS-CoV-2 ; Cholesterol, HDL ; *Dyslipidemias/epidemiology ; }, abstract = {BACKGROUND: Non-clinical evidence and a few human studies with short follow-ups suggest increased risk of dyslipidaemia in the post-acute phase of COVID-19 (ie, >30 days after SARS-CoV-2 infection). However, detailed large-scale controlled studies with longer follow-ups and in-depth assessment of the risks and burdens of incident dyslipidaemia in the post-acute phase of COVID-19 are not yet available. We, therefore, aimed to examine the risks and 1-year burdens of incident dyslipidaemia in the post-acute phase of COVID-19 among people who survive the first 30 days of SARS-CoV-2 infection.

METHODS: In this cohort study, we used the national health-care databases of the US Department of Veterans Affairs to build a cohort of 51 919 participants who had a positive COVID-19 test and survived the first 30 days of infection between March 1, 2020, and Jan 15, 2021; a non-infected contemporary control group (n=2 647 654) that enrolled patients between March 1, 2020, and Jan 15, 2021; and a historical control group (n=2 539 941) that enrolled patients between March 1, 2018, and Jan 15, 2019. Control groups had no evidence of SARS-CoV-2 infection, and participants in all three cohorts were free of dyslipidaemia before cohort enrolment. We then used inverse probability weighting using predefined and algorithmically-selected high dimensional variables to estimate the risks and 1-year burdens of incident dyslipidaemia, lipid-lowering medications use, and a composite of these outcomes. We reported two measures of risk: hazard ratios (HRs) and burden per 1000 people at 12 months. Additionally, we estimated the risks and burdens of incident dyslipidaemia outcomes in mutually exclusive groups based on the care setting of the acute infection (ie, participants who were non-hospitalised, hospitalised, or admitted to intensive care during the acute phase of SARS-CoV-2 infection).

FINDINGS: In the post-acute phase of the SARS-CoV-2 infection, compared with the non-infected contemporary control group, those in the COVID-19 group had higher risks and burdens of incident dyslipidaemia, including total cholesterol greater than 200 mg/dL (hazard ratio [HR] 1·26, 95% CI 1·22-1·29; burden 22·46, 95% CI 19·14-25·87 per 1000 people at 1 year), triglycerides greater than 150 mg/dL (1·27, 1·23-1·31; 22·03, 18·85-25·30), LDL cholesterol greater than 130 mg/dL (1·24, 1·20-1·29; 18·00, 14·98-21·11), and HDL cholesterol lower than 40 mg/dL (1·20, 1·16-1·25; 15·58, 12·52-18·73). The risk and burden of a composite of these abnormal lipid laboratory outcomes were 1·24 (95% CI 1·21-1·27) and 39·19 (95% CI 34·71-43·73), respectively. There was also increased risk and burden of incident lipid-lowering medications use (HR 1·54, 95% CI 1·48-1·61; burden 25·50, 95% CI 22·61-28·50). A composite of any dyslipidaemia outcome (laboratory abnormality or lipid-lowering medications use) yielded an HR of 1·31 (95% CI 1·28-1·34) and a burden of 54·03 (95% CI 49·21-58·92). The risks and burdens of these post-acute outcomes increased in a graded fashion corresponding to the severity of the acute phase of COVID-19 infection (ie, whether patients were non-hospitalised, hospitalised, or admitted to intensive care). The results were consistent in analyses comparing the COVID-19 group to the non-infected historical control group.

INTERPRETATION: Our findings suggest increased risks and 1-year burdens of incident dyslipidaemia and incident lipid-lowering medications use in the post-acute phase of COVID-19 infection. Post-acute care for those with COVID-19 should involve attention to dyslipidaemia as a potential post-acute sequela of SARS-CoV-2 infection.

FUNDING: US Department of Veterans Affairs.}, } @article {pmid36623391, year = {2023}, author = {Lemogne, C and Gouraud, C and Pitron, V and Ranque, B}, title = {Why the hypothesis of psychological mechanisms in long COVID is worth considering.}, journal = {Journal of psychosomatic research}, volume = {165}, number = {}, pages = {111135}, pmid = {36623391}, issn = {1879-1360}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Nocebo Effect ; }, } @article {pmid36620963, year = {2023}, author = {Saunders, C and Sperling, S and Bendstrup, E}, title = {A new paradigm is needed to explain long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {2}, pages = {e12-e13}, doi = {10.1016/S2213-2600(22)00501-X}, pmid = {36620963}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid36620918, year = {2023}, author = {Mazurkiewicz, I and Chatys-Bogacka, Z and Slowik, J and Klich-Raczka, A and Fedyk-Lukasik, M and Slowik, A and Wnuk, M and Drabik, L}, title = {Fatigue after COVID-19 in non-hospitalized patients according to sex.}, journal = {Brain and behavior}, volume = {13}, number = {2}, pages = {e2849}, pmid = {36620918}, issn = {2162-3279}, mesh = {Humans ; Female ; Male ; Adolescent ; *COVID-19/complications ; SARS-CoV-2 ; Retrospective Studies ; *Fatigue Syndrome, Chronic/epidemiology ; Headache ; }, abstract = {BACKGROUND: Limited evidence exists on sex differences in post-COVID fatigue among non-hospitalized patients. Therefore, aim of the study was to evaluate the course of chronic fatigue symptoms in non-hospitalized subjects with the SARS-CoV-2 infection, according to sex.

METHODS: Patients and staff from the University Hospital in Krakow anonymously and retrospectively completed neuropsychological questionnaire that included eight symptoms of chronic fatigue syndrome. The presence of these symptoms was assessed before COVID-19 and 0-4, 4-12, and >12 weeks postinfection. The inclusion criteria were as follows: age 18 or more years, >12 weeks since the onset of the SARS-CoV-2 infection, and diagnosis confirmed by the RT-PCR from anasopharyngeal swab.

RESULTS: We included 303 patients (79.53% women, 47.52% medical personnel) assessed retrospectively after a median of 30 (interquartile range: 23-35) weeks since the onset of symptoms. A higher prevalence of at least one chronic fatigue symptom was found in females in all time intervals after the onset of COVID-19 compared to males (p < .036). Women, compared to men, more often experienced persistent fatigue, not caused by effort and persisting after rest (for <4 weeks, odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.13-4.73; for 4-12 weeks, OR = 1.95, 95% CI: 1.06-3.61), non-restorative sleep (for <4 weeks, OR = 2.17, 95% CI: 1.23-3.81; for >12 weeks, OR = 1.95, 95% CI: 1.03-3.71), and sore throat (for <4 weeks, OR = 1.97, 95% CI: 1.03-3.78; for 4-12 weeks, OR = 2.76, 95% CI: 1.05-7.27). Sex differences in headache, arthralgia, and prolonged postexercise fatigue were observed only during the first 4 weeks (OR = 2.59, 95% CI: 1.45-4.60, OR = 2.97, 95% CI: 1.02-8.64, and OR = 1.87, 95% CI: 1.01-3.51, respectively). There were no differences between women and men in myalgia and self-reported lymph node enlargement.

CONCLUSIONS: The course of post-COVID fatigue differs significantly between sexes in non-hospitalized individuals with COVID-19, with women more often suffering from persistent fatigue, not caused by effort and persisting after rest, non-restorative sleep, and sore throat.}, } @article {pmid36619270, year = {2022}, author = {Jadali, Z and Jalil, AT}, title = {Gastrointestinal Involvement in Long COVID and Potential Pathogenic Mechanisms.}, journal = {Middle East journal of digestive diseases}, volume = {14}, number = {3}, pages = {359-360}, pmid = {36619270}, issn = {2008-5230}, } @article {pmid36618714, year = {2023}, author = {Fessel, J}, title = {Fluoxetine plus lithium for treatment of mental health impairment in Long Covid.}, journal = {Discover mental health}, volume = {3}, number = {1}, pages = {1}, pmid = {36618714}, issn = {2731-4383}, abstract = {PURPOSES: (1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate treatment based upon the brain cells that are dominantly affected.

METHODS: (1) Review the reports relating to the mental symptoms occurring in Long Covid. (2) Review the drugs that address the brain cells affected in Long Covid, and suggest pharmacotherapy for those patients whose response to psychotherapy is suboptimal.

RESULTS: Long Covid affects ~ 10% of patients infected by SARS-CoV-2, and mental symptoms affect ~ 20% of persons with Long Covid. The brain cell-types that have been demonstrated as dominantly affected in Long Covid are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types. Low dosage of each is likely to be well-tolerated and to cause neither clinically important adverse events (AE) nor serious adverse events (SAE).

CONCLUSION: For those patients whose response to psychotherapy is suboptimal, lithium and fluoxetine should be administered in combination for both depth of benefit and reduction of dosages.}, } @article {pmid36618501, year = {2023}, author = {Nishi, K and Yoshimoto, S and Tanaka, T and Kimura, S and Shinchi, Y and Yamano, T}, title = {A Potential Novel Treatment for Chronic Cough in Long COVID Patients: Clearance of Epipharyngeal Residual SARS-CoV-2 Spike RNA by Epipharyngeal Abrasive Therapy.}, journal = {Cureus}, volume = {15}, number = {1}, pages = {e33421}, pmid = {36618501}, issn = {2168-8184}, abstract = {A major target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the epipharyngeal mucosa. Epipharyngeal abrasive therapy (EAT) is a Japanese treatment for chronic epipharyngitis. EAT is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. Here, we present a case of a 21-year-old man with chronic coughing that persisted for four months after a diagnosis of mild coronavirus disease 2019 (COVID-19), who was treated by EAT. We diagnosed chronic epipharyngitis as the cause of the chronic cough after the SARS-CoV-2 infection. SARS-CoV-2 spike RNA had persisted in the epipharyngeal mucosa of this Long COVID patient. EAT was performed once a week for three months, which eliminated residual SARS-CoV-2 RNA and reduced epipharyngeal inflammation. Moreover, a reduction in the expression of proinflammatory cytokines was found by histopathological examination. We speculate that the virus was excreted with the drainage induced by EAT, which stopped the secretion of proinflammatory cytokines. This case study suggests that EAT is a useful treatment for chronic epipharyngitis involving long COVID.}, } @article {pmid36615143, year = {2023}, author = {Siekacz, K and Kumor-Kisielewska, A and Miłkowska-Dymanowska, J and Pietrusińska, M and Bartczak, K and Majewski, S and Stańczyk, A and Piotrowski, WJ and Białas, AJ}, title = {Soluble ITGaM and ITGb2 Integrin Subunits Are Involved in Long-Term Pulmonary Complications after COVID-19 Infection.}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36615143}, issn = {2077-0383}, abstract = {(1) Introduction: The role of soluble integrins in post-COVID-19 complications is unclear, especially in long-term pulmonary lesions. The purpose of this study was to investigate the association between soluble ITGa2, ITGaM and ITGb2 integrin subunits and long COVID-19 pulmonary complications. (2) Methodology: Post-COVID-19 patients were enrolled. According to the evidence of persistent interstitial lung lesions on CT, patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for further investigation (40 subjects for each group). Levels of ITGa2, ITGaM and ITGb2 integrin subunits were determined by ELISA assay. (3) Results: The serum concentration of sITGaM and sITGb2 were significantly higher in the P(+) group (sITGaM 18.63 ng/mL [IQR 14.17-28.83] vs. 14.75 ng/mL [IQR 10.91-20] p = 0.01 and sITGb2 10.55 ng/mL [IQR 6.53-15.83] vs. 6.34 ng/mL [IQR 4.98-9.68] p = 0.002). We observed a statistically significant correlation between sITGaM and sITGb2 elevation in the P(+) group (R = 0.42; p = 0.01). Patients from the P(+) group had a lower (1.82 +/-0.84 G/L) lymphocyte level than the P(-)group (2.28 +/-0.79 G/L), p = 0.03. Furthermore, we observed an inverse correlation in the P(-) group between blood lymphocyte count and sITGb2 integrin subunit levels (R = -0.49 p = 0.01). (4) Conclusions: Elevated concentrations of sITGaM and sITGb2 were associated with long-term pulmonary complications in post-COVID-19 patients. Both sITGaM and sITGb2 may be promising biomarkers for predicting pulmonary complications and could be a potential target for therapeutic intervention in post-COVID-19 patients.}, } @article {pmid36614987, year = {2022}, author = {Sabatino, J and Di Chiara, C and Di Candia, A and Sirico, D and Donà, D and Fumanelli, J and Basso, A and Pogacnik, P and Cuppini, E and Romano, LR and Castaldi, B and Reffo, E and Cerutti, A and Biffanti, R and Cozzani, S and Giaquinto, C and Di Salvo, G}, title = {Mid- and Long-Term Atrio-Ventricular Functional Changes in Children after Recovery from COVID-19.}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36614987}, issn = {2077-0383}, support = {VERDI (101045989)//European Union/ ; }, abstract = {Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE). Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3−18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180−240 days, >240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL). Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs. Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population.}, } @article {pmid36614901, year = {2022}, author = {Menezes Junior, ADS and Schröder, AA and Botelho, SM and Resende, AL}, title = {Cardiac Autonomic Function in Long COVID-19 Using Heart Rate Variability: An Observational Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36614901}, issn = {2077-0383}, abstract = {BACKGROUND: Heart rate variability is a non-invasive, measurable, and established autonomic nervous system test. Long-term COVID-19 sequelae are unclear; however, acute symptoms have been studied.

OBJECTIVES: To determine autonomic cardiac differences between long COVID-19 patients and healthy controls and evaluate associations among symptoms, comorbidities, and laboratory findings.

METHODS: This single-center study included long COVID-19 patients and healthy controls. The heart rate variability (HRV), a quantitative marker of autonomic activity, was monitored for 24 h using an ambulatory electrocardiogram system. HRV indices were compared between case and control groups. Symptom frequency and inflammatory markers were evaluated. A significant statistical level of 5% (p-value 0.05) was adopted.

RESULTS: A total of 47 long COVID-19 patients were compared to 42 healthy controls. Patients averaged 43.8 (SD14.8) years old, and 60.3% were female. In total, 52.5% of patients had moderate illness. Post-exercise dyspnea was most common (71.6%), and 53.2% lacked comorbidities. CNP, D-dimer, and CRP levels were elevated (p-values of 0.0098, 0.0023, and 0.0015, respectively). The control group had greater SDNN24 and SDANNI (OR = 0.98 (0.97 to 0.99; p = 0.01)). Increased low-frequency (LF) indices in COVID-19 patients (OR = 1.002 (1.0001 to 1.004; p = 0.030)) and high-frequency (HF) indices in the control group (OR = 0.987 (0.98 to 0.995; p = 0.001)) were also associated.

CONCLUSIONS: Patients with long COVID-19 had lower HF values than healthy individuals. These variations are associated with increased parasympathetic activity, which may be related to long COVID-19 symptoms and inflammatory laboratory findings.}, } @article {pmid36614882, year = {2022}, author = {Mattioli, AV and Selleri, V and Zanini, G and Nasi, M and Pinti, M and Stefanelli, C and Fedele, F and Gallina, S}, title = {Physical Activity and Diet in Older Women: A Narrative Review.}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36614882}, issn = {2077-0383}, abstract = {Physical activity and diet are essential for maintaining good health and preventing the development of non-communicable diseases, especially in the older adults. One aspect that is often over-looked is the different response between men and women to exercise and nutrients. The body's response to exercise and to different nutrients as well as the choice of foods is different in the two sexes and is strongly influenced by the different hormonal ages in women. The present narrative review analyzes the effects of gender on nutrition and physical activity in older women. Understanding which components of diet and physical activity affect the health status of older women would help target non-pharmacological but lifestyle-related therapeutic interventions. It is interesting to note that this analysis shows a lack of studies dedicated to older women and a lack of studies dedicated to the interactions between diet and physical activity in women. Gender medicine is a current need that still finds little evidence.}, } @article {pmid36614874, year = {2022}, author = {Chung, TH and Azar, A}, title = {Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC).}, journal = {Journal of clinical medicine}, volume = {12}, number = {1}, pages = {}, pmid = {36614874}, issn = {2077-0383}, abstract = {The novel SARS-CoV-2 virus and resulting COVID-19 global pandemic emerged in 2019 and continues into 2022. While mortality from COVID-19 is slowly declining, a subset of patients have developed chronic, debilitating symptoms following complete recovery from acute infection with COVID-19. Termed as post-acute sequelae of SARS-CoV-2 syndrome (PASC), the underlying pathophysiology of PASC is still not well understood. Given the similarity between the clinical phenotypes of PASC and postural orthostatic tachycardia syndrome (POTS), it has been postulated that dysautonomia may play a role in the pathophysiology of PASC. However, there have been only a few studies that have examined autonomic function in PASC. In this retrospective study, we performed an analysis of autonomic nerve function testing in PASC patients and compared the results with those of POTS patients and healthy controls. Our results suggest that a significant number of PASC patients have abnormal autonomic function tests, and their clinical features are indistinguishable from POTS.}, } @article {pmid36613731, year = {2022}, author = {Tyagi, SC and Pushpakumar, S and Sen, U and Mokshagundam, SPL and Kalra, DK and Saad, MA and Singh, M}, title = {COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613731}, issn = {1422-0067}, support = {HL-74185, HL-139047, DK116591 and AR-71789/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Matrix Metalloproteinase 9/metabolism ; Mice, Inbred mdx ; Tumor Necrosis Factor-alpha/metabolism ; Post-Acute COVID-19 Syndrome ; Neopterin/metabolism ; *COVID-19/pathology ; SARS-CoV-2 ; *Muscular Dystrophy, Duchenne/genetics ; Fibrosis ; Muscle, Skeletal/metabolism ; Disease Models, Animal ; }, abstract = {Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9[-/-]) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.}, } @article {pmid36613462, year = {2022}, author = {Dufrusine, B and Valentinuzzi, S and Bibbò, S and Damiani, V and Lanuti, P and Pieragostino, D and Del Boccio, P and D'Alessandro, E and Rabottini, A and Berghella, A and Allocati, N and Falasca, K and Ucciferri, C and Mucedola, F and Di Perna, M and Martino, L and Vecchiet, J and De Laurenzi, V and Dainese, E}, title = {Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613462}, issn = {1422-0067}, support = {FISR2020IP_03845//Italian Ministry of University and Research/ ; }, mesh = {Humans ; *Iron/metabolism ; Lipocalin-2 ; Post-Acute COVID-19 Syndrome ; Arachidonate 5-Lipoxygenase/metabolism ; Proteomics ; *COVID-19 ; Biomarkers ; }, abstract = {Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.}, } @article {pmid36613170, year = {2023}, author = {Lapa, J and Rosa, D and Mendes, JPL and Deusdará, R and Romero, GAS}, title = {Prevalence and Associated Factors of Post-COVID-19 Syndrome in a Brazilian Cohort after 3 and 6 Months of Hospital Discharge.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36613170}, issn = {1660-4601}, mesh = {Humans ; Female ; Brazil/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; *Hypercholesterolemia ; Prevalence ; *COVID-19/epidemiology ; Hospitalization ; Fatigue ; Hospitals, Public ; Obesity ; Memory Disorders ; }, abstract = {(1) Objectives: To evaluate the frequency and factors associated with the Post-COVID-19 Syndrome (PCS) in COVID-19 survivors after 3 and 6 months of hospital discharge; (2) Methods: We conducted a cohort study with patients who were hospitalized with COVID-19 in a referral public hospital in Brasília, Federal District, Brazil. After 3 and 6 months of discharge, patients answered a questionnaire about PCS symptoms. Poisson regression with robust variance was used to estimate the crude and adjusted prevalence ratios (PR and aPR) of PCS. (3) Results: The prevalence of PCS was 81% and 61% after 3 and 6 months of hospital discharge, respectively. The main symptoms after 3 months of discharge were hair loss (44%), fatigue (42%), and memory loss (39%); while after 6 months, they were memory loss (29%) and fatigue (27%). In the multivariate analysis, the main factor associated with PCS was female gender (aPR): 1.28 (1.16-1.41) and 1.60 (1.34-1.90), 3 and 6 months after hospital discharge, respectively. Hypercholesterolemia was also associated with PCS after 3 months aPR of 1.15 (1.04-1.27). After 6 months of discharge, obesity [aPR: 1.22 (1.03-1.45)] and pronation [aPR: 1.15 (1.06-1.25)] were relevant associated factors. (4) Conclusions: The prevalence of PCS was high in COVID-19 survivors who had the moderate and severe forms of the disease. Memory loss was the most persistent symptom. Our data pointed to female gender, hypercholesterolemia, obesity, and pronation during hospitalization as relevant PCS-associated risk factors.}, } @article {pmid36612816, year = {2022}, author = {Craparo, G and La Rosa, VL and Commodari, E and Marino, G and Vezzoli, M and Faraci, P and Vicario, CM and Cinà, GS and Colombi, M and Arcoleo, G and Severino, M and Costanzo, G and Gori, A and Mangiapane, E}, title = {What Is the Role of Psychological Factors in Long COVID Syndrome? Latent Class Analysis in a Sample of Patients Recovered from COVID-19.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612816}, issn = {1660-4601}, mesh = {Male ; Humans ; Female ; Post-Acute COVID-19 Syndrome ; *Stress Disorders, Post-Traumatic/psychology ; Latent Class Analysis ; *COVID-19/epidemiology ; Affective Symptoms ; }, abstract = {Background: This study aimed to identify clusters of long COVID-19 symptoms using latent class analysis and investigate the psychological factors involved in the onset of this syndrome. Method: Five hundred and six subjects recovering from COVID-19 completed a series of standardized questionnaires to evaluate the personality traits, alexithymia, and post-traumatic stress. Results: Five classes were identified: Brain fog (31.82%), No symptoms (20.95%), Sensory disorders (18.77%), Breath impairment (17.59%), and Multiple disorders (10.87%). Women reported post-COVID-19 respiratory symptoms and multiple disorders to a greater extent than men. Hospitalized subjects were more likely to report persistent symptoms after COVID-19 than asymptomatic or home-treated subjects. Antagonism, hyperarousal, and difficulty identifying emotions significantly predicted post COVID-19 symptoms. Conclusions: These findings open new questions for research on long COVID-19 and how states of emotional dysregulation can alter the physiological processes of the body and contribute to the onset of organic pathologies.}, } @article {pmid36612782, year = {2022}, author = {Samper-Pardo, M and León-Herrera, S and Oliván-Blázquez, B and Benedé-Azagra, B and Magallón-Botaya, R and Gómez-Soria, I and Calatayud, E and Aguilar-Latorre, A and Méndez-López, F and Pérez-Palomares, S and Cobos-Rincón, A and Valero-Errazu, D and Sagarra-Romero, L and Sánchez-Recio, R}, title = {Development and Validation of a Mobile Application as an Adjuvant Treatment for People Diagnosed with Long COVID-19: Protocol for a Co-Creation Study of a Health Asset and an Analysis of Its Effectiveness and Cost-Effectiveness.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612782}, issn = {1660-4601}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Cost-Benefit Analysis ; *Mobile Applications ; Quality of Life ; *COVID-19 ; Randomized Controlled Trials as Topic ; }, abstract = {OBJECTIVE: To analyse the overall effectiveness and cost-efficiency of a mobile application (APP) as a community health asset (HA) with recommendations and recovery exercises created bearing in mind the main symptoms presented by patients in order to improve their quality of life, as well as other secondary variables, such as the number and severity of ongoing symptoms, physical and cognitive functions, affective state, and sleep quality.

METHODS: The first step was to design and develop the technologic community resource, the APP, following the steps involved in the process of recommending health assets (RHA). After this, a protocol of a randomised clinical trial for analysing its effectiveness and cost-efficiency as a HA was developed. The participants will be assigned to: (1st) usual treatment by the primary care practitioner (TAU), as a control group; and (2nd) TAU + use of the APP as a HA and adjuvant treatment in their recovery + three motivational interviews (MI), as an interventional group. An evaluation will be carried out at baseline with further assessments three and six months following the end of the intervention.

DISCUSSION: Although research and care for these patients are still in their initial stages, it is necessary to equip patients and health care practitioners with tools to assist in their recovery. Furthermore, enhanced motivation can be achieved through telerehabilitation (TR).}, } @article {pmid36612567, year = {2022}, author = {Binns, CW and Lee, MK and Doan, TTD and Lee, A and Pham, M and Zhao, Y}, title = {COVID and Gender: A Narrative Review of the Asia-Pacific Region.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612567}, issn = {1660-4601}, mesh = {Male ; Female ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics/prevention & control ; Communicable Disease Control ; Asia/epidemiology ; }, abstract = {The COVID-19 pandemic has been the largest infectious disease epidemic to affect the human race since the great influenza pandemic of 1918-19 and is close to approaching the number of deaths from the earlier epidemic. A review of available data and the numerous currently available studies on COVID-19 shows that the rate of clinical cases is about 10% greater in females than males in Asia. However, the number of deaths is greater in males than in females. Women are more likely to experience the psychological effects of COVID-19 during and after acute infections. A significant proportion of acute COVID-19 infections continue and their prolonged symptoms have been reported. Further studies are needed, including detailed serology, to measure and monitor the incidence of COVID-19. The pandemic has had a widespread impact on broader societies including shortages of food, lockdowns and isolation. The number of orphans in developing countries has increased. Women have had to bear the major impacts of these community effects. More research is required to develop better vaccines acting against new strains of the virus and to develop systems to distribute vaccines to all people.}, } @article {pmid36612505, year = {2022}, author = {Perrin, PB and Ramos-Usuga, D and West, SJ and Merced, K and Klyce, DW and Lequerica, AH and Olabarrieta-Landa, L and Alzueta, E and Baker, FC and Iacovides, S and Cortes, M and Arango-Lasprilla, JC}, title = {Network Analysis of Neurobehavioral Symptom Patterns in an International Sample of Spanish-Speakers with a History of COVID-19 and Controls.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612505}, issn = {1660-4601}, mesh = {Adult ; Humans ; Control Groups ; *COVID-19/complications/epidemiology ; Fatigue ; Headache ; Pandemics ; Psychometrics ; Dizziness ; }, abstract = {(1) Background: Psychometric network analysis provides a novel statistical approach allowing researchers to model clusters of related symptoms as a dynamic system. This study applied network analysis to investigate the patterns of somatic, cognitive, and affective neurobehavioral symptoms in an international sample of Spanish-speaking individuals with a history of COVID-19 positivity and non-COVID controls; (2) methods: the sample (n = 1093) included 650 adults from 26 countries who reported having previously tested positive for COVID-19 (COVID+) through a viral and/or antigen test (average of 147 days since diagnosis). The control group (COVID-) was comprised of 443 adults from 20 countries who had completed the survey prior to the COVID-19 pandemic; (3) results: relative to the COVID- network, the COVID+ network was very well-connected, such that each neurobehavioral symptom was positively connected to the network. The organize-to-headache and dizzy-to-balance connections in the COVID+ network were stronger than in the COVID- network. The hearing, numbness, and tense symptoms were more central to the COVID+ network with the latter connected to the sleep, fatigue, and frustrated symptoms. The COVID- network was largely disjointed, with most of the somatosensory symptoms forming their own cluster with no connections to other symptom groups and fatigue not being connected to any other symptom. The cognitive and affective symptoms in the COVID- network were also largely connected to symptoms from within their own groups; (4) conclusions: These findings suggest that many of the long-term neurobehavioral symptoms of COVID-19 form a discernable network and that headaches, frustration, hearing problems, forgetfulness, and tension are the most central symptoms. Cognitive and behavioral rehabilitation strategies targeting these central symptom network features may hold promise to help fracture the lingering symptom network of COVID-19.}, } @article {pmid36611411, year = {2022}, author = {Eligulashvili, A and Darrell, M and Miller, C and Lee, J and Congdon, S and Lee, JS and Hsu, K and Yee, J and Hou, W and Islam, M and Duong, TQ}, title = {COVID-19 Patients in the COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {36611411}, issn = {2075-4418}, abstract = {Background: Early in the pandemic, we established COVID-19 Recovery and Engagement (CORE) Clinics in the Bronx and implemented a detailed evaluation protocol to assess physical, emotional, and cognitive function, pulmonary function tests, and imaging for COVID-19 survivors. Here, we report our findings up to five months post-acute COVID-19. Methods: Main outcomes and measures included pulmonary function tests, imaging tests, and a battery of symptom, physical, emotional, and cognitive assessments 5 months post-acute COVID-19. Findings: Dyspnea, fatigue, decreased exercise tolerance, brain fog, and shortness of breath were the most common symptoms but there were generally no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Many patients had abnormal physical, emotional, and cognitive scores, but most functioned independently; there were no significant differences between hospitalized and non-hospitalized cohorts (p > 0.05). Six-minute walk tests, lung ultrasound, and diaphragm excursion were abnormal but only in the hospitalized cohort. Pulmonary function tests showed moderately restrictive pulmonary function only in the hospitalized cohort but no obstructive pulmonary function. Newly detected major neurological events, microvascular disease, atrophy, and white-matter changes were rare, but lung opacity and fibrosis-like findings were common after acute COVID-19. Interpretation: Many COVID-19 survivors experienced moderately restrictive pulmonary function, and significant symptoms across the physical, emotional, and cognitive health domains. Newly detected brain imaging abnormalities were rare, but lung imaging abnormalities were common. This study provides insights into post-acute sequelae following SARS-CoV-2 infection in neurological and pulmonary systems which may be used to support at-risk patients and develop effective screening methods and interventions.}, } @article {pmid36611316, year = {2022}, author = {Núñez-Cortés, R and Flor-Rufino, C and Martínez-Arnau, FM and Arnal-Gómez, A and Espinoza-Bravo, C and Hernández-Guillén, D and Cortés-Amador, S}, title = {Feasibility of the 30 s Sit-to-Stand Test in the Telehealth Setting and Its Relationship to Persistent Symptoms in Non-Hospitalized Patients with Long COVID.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {36611316}, issn = {2075-4418}, abstract = {Fatigue, dyspnea and pain are the main limitations of patients with long COVID. The aim of this study was to determine the feasibility of the 30 s sit-to-stand (30s-STS) test in the telehealth setting and its relationship to persistent symptoms in a sample of non-hospitalized patients with long COVID. A cross-sectional study was conducted in community patients with long COVID. Data collection and assessments were performed by videoconference and consisted of the fatigue assessment scale (FAS), London activity of daily living scale (LCADL), post-COVID-19 functional status (PCFS) and European quality of life questionnaire (EQ-5D-5L), including the pain/discomfort dimension. The 30s-STS test was performed using a standardized protocol adapted for remote use, and the modified Borg scale (0−10) was used to assess dyspnea and lower limb fatigue immediately after the test. The feasibility of the 30s-STS test was assessed by the proportion of eligible participants who were able to complete the test. Safety was assessed by the number of adverse events that occurred during the test. Seventy-nine participants were included (median age: 44 years, 86.1% women). Performance in the 30s-STS test was 11.5 ± 3.2 repetitions with 60.8% of the sample below reference values. All eligible participants were able to complete the test. No adverse events were reported during the evaluation. Participants with lower 30s-STS performance had more fatigue and dyspnea, worse quality of life, more severe pain/discomfort, and worse functional status (p < 0.05). A significant correlation was obtained between LCADL and dyspnea, reported on the Borg scale (0−10) post 30s-STS (r = 0.71; p < 0.001). In conclusion, the 30s-STS test proved to be a feasible test to implement in the telehealth setting and is related to fatigue, dyspnea, quality of life and pain in non-hospitalized patients with long COVID. Clinicians may use this test when assessment of the physical sequelae of COVID-19 in the face-to-face setting is not possible.}, } @article {pmid36610599, year = {2023}, author = {Gamberini, G and Masuccio, FG and Cerrato, M and Strazzacappa, M and Ferraro, D and Solaro, C}, title = {Previously independent patients with mild-symptomatic COVID-19 are at high risk of developing cognitive impairment but not depression or anxiety.}, journal = {Journal of affective disorders}, volume = {324}, number = {}, pages = {645-651}, pmid = {36610599}, issn = {1573-2517}, mesh = {Humans ; Aged ; SARS-CoV-2 ; *COVID-19 ; Hospitalization ; *Nervous System Diseases ; Anxiety/epidemiology ; *Cognitive Dysfunction/diagnosis/epidemiology/etiology ; }, abstract = {OBJECTIVES: The aim of the study was to explore the cognitive functions of a large sample of hospitalised subjects with mild symptomatic Coronavirus Disease (COVID-19) who were previously independent at home and without neurological diseases.

METHODS: Patients admitted in a COVID-19 Unit for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection between November 2020 and March 2021 were recruited. Inclusion criteria were: being independent at home before the infection, radiologically confirmed COVID-19 pneumonia, positive reverse transcriptase-polymerase chain reaction nasopharyngeal swab and no oxygen supplementation at the time of evaluation.

EXCLUSION CRITERIA: cognitive impairment or neurological diseases previous to the infection, delirium episodes, and history of any mechanical ventilation use. They were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A).

RESULTS: Out of 522 subjects admitted in the COVID-19 Unit, 90 were enrolled [mean age = 68.32(11.99); 46M/44F]. An impaired MoCA (cut-off < 23) was found in 60 subjects (66.66 %). Pathological scores were obtained by 36.7 % of the subjects with <65 years and 78.3 % of those older than 65 years. A high prevalence of executive function and memory impairment was detected.

CONCLUSIONS: The results underline a high rate of cognitive impairment in previously independent mild COVID-19 patients. This might represent a potential threat for the everyday independence of these patients due to the consequences on everyday life activities and work following discharge from hospital. These subjects should, therefore, be monitored in order to allow a better understanding of the progression and consequences of the so-called "Long COVID".}, } @article {pmid36610206, year = {2023}, author = {Noda, Y and Sato, A and Shichi, M and Sato, A and Fujii, K and Iwasa, M and Nagano, Y and Kitahata, R and Osawa, R}, title = {Real world research on transcranial magnetic stimulation treatment strategies for neuropsychiatric symptoms with long-COVID in Japan.}, journal = {Asian journal of psychiatry}, volume = {81}, number = {}, pages = {103438}, pmid = {36610206}, issn = {1876-2026}, mesh = {Female ; Humans ; *COVID-19/etiology ; *Depressive Disorder, Major ; *Fatigue Syndrome, Chronic/etiology ; Japan ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; Transcranial Magnetic Stimulation/methods ; Treatment Outcome ; }, abstract = {The number of patients suffering from long-COVID is currently increasing rapidly, even after the acute symptoms of COVID-19 have improved. The objective of this study was to investigate the effects of a pilot transcranial magnetic stimulation (TMS) treatment on neuropsychiatric symptoms caused by long-COVID. In this study, we examined the efficacy of the TMS treatment protocol, which has been established to be effective in refractory depression, by applying it to patients who sought TMS treatment for neuropsychiatric symptoms caused by long-COVID at TMS clinics in Tokyo, Japan in the context of the real world TMS registry study in Japan. Of the 23 patients (13 females) with long-COVID included in this case series, the main neuropsychiatric symptoms were chronic fatigue (n = 12) and cognitive dysfunction (n = 11), but most patients also showed mild depressive symptoms. The mean score on the Montgomery-Åsberg Depression Rating Scale before TMS treatment was 21.2, which improved to 9.8 after treatment. Similarly, the score on the Performance Status, which assesses the degree of fatigue, improved from 5.4 to 4.2, and the score on the Perceived Deficits Questionnaire-Depression 5-item, which reflects cognitive function, improved from 10.0 to 6.3. Although a few patients complained of pain at the stimulation site during the TMS as a side effect, there were no serious adverse events. Despite the limitations of this open-label pilot study, the TMS protocol implemented in this study may have beneficial effects on neuropsychiatric symptoms caused by long-COVID, including depressive symptoms, chronic fatigue, and cognitive impairment. These preliminary findings warrant further validation in randomized controlled trials.}, } @article {pmid36609778, year = {2023}, author = {Teng, L and Song, X and Zhang, M and Han, Y and Chang, G and Chang, W and Shen, Z}, title = {The pattern of cytokines expression and dynamic changes of renal function at 6 months in patients with Omicron COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28477}, doi = {10.1002/jmv.28477}, pmid = {36609778}, issn = {1096-9071}, mesh = {Humans ; Cytokines ; Creatinine ; Post-Acute COVID-19 Syndrome ; Interleukin-5 ; *COVID-19 ; Transforming Growth Factor beta ; Glomerular Filtration Rate ; Kidney/physiology ; *Renal Insufficiency, Chronic ; }, abstract = {To analyze the dynamic changes of renal function longitudinally and investigate the cytokine profiles at 6 months in patients with Omicron COVID-19. Forty-seven patients with a proven diagnosis of Omicron COVID-19 from January to February 2022 attended a 6-month follow-up after discharge at Tianjin First Central Hospital. The demographic parameters, clinical features, and laboratory indexes were collected during hospitalization and 6 months after discharge. The serum cytokine levels at 6 months were also assessed. Patients were grouped according to with or without kidney involvement at admission. The levels of serum creatinine and estimated glomerular filtration rate (eGFR) were all normal both in the hospital and at follow-up. Whereas, compared with renal function in the hospital, serum creatinine levels at 6 months increased remarkably; meanwhile, eGFR decreased significantly in all patients. The serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, and TNF-α and IFN-γ significantly decreased and TGF-β remarkably increased in the kidney involvement group. The serum levels of IL-2 and IL-5 were positively correlated with age; contrarily, TGF-β showed a negative correlation with aging. The younger was an independent risk factor of the higher TGF-β levels. Omicron patients showed a decline in renal function at follow-up, reflecting the trend of CKD. Serum cytokine profiles were characterized with the majority of cytokines decreased and TGF-β increased in the kidney involvement group; the latter may be used as a sign of CKD. The tendency of CKD is one of the manifestations of long COVID and deserves attention.}, } @article {pmid36608066, year = {2022}, author = {Manu, P}, title = {Aromatherapy and Fermented Fruits for Long COVID: Placebo-Controlled Placebo Trials?.}, journal = {American journal of therapeutics}, volume = {29}, number = {6}, pages = {e649-e650}, doi = {10.1097/MJT.0000000000001574}, pmid = {36608066}, issn = {1536-3686}, mesh = {Humans ; *Aromatherapy ; Fruit ; Plant Oils ; *Post-Acute COVID-19 Syndrome/therapy ; Randomized Controlled Trials as Topic ; Placebos ; Fermented Foods ; }, } @article {pmid36607266, year = {2023}, author = {Buonsenso, D}, title = {It is OK to tell patients with long COVID that we don't know much about the condition yet.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {4}, pages = {585-586}, doi = {10.1111/apa.16658}, pmid = {36607266}, issn = {1651-2227}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36606602, year = {2023}, author = {Li, X and Yin, W and Li, A and Li, D and Gao, X and Wang, R and Cui, B and Qiu, S and Li, R and Jia, L and Zuo, C and Zhang, L and Li, M}, title = {ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus.}, journal = {Journal of medical virology}, volume = {95}, number = {2}, pages = {e28470}, doi = {10.1002/jmv.28470}, pmid = {36606602}, issn = {1096-9071}, mesh = {Male ; Humans ; Mice ; Animals ; *COVID-19 ; Peptidyl-Dipeptidase A/metabolism ; SARS-CoV-2/metabolism ; Angiotensin-Converting Enzyme 2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; Positron Emission Tomography Computed Tomography ; }, abstract = {Due to the COVID-19 pandemic, a series of sequelae, such as fatigue, tachypnea, and ageusia, appeared in long COVID patients, but the pathological basis was still uncertain. The targeted radiopharmaceuticals were of potential to systemically and dynamically trace the pathological changes. For the key ACE2 protein in the virus-host interaction, [68] Ga-cyc-DX600 was developed on the basis of DX600 as a PET tracer of ACE2 fluctuation and maintained the ability in differentiating ACE and ACE2. In the temporary infection model inhaled with the radio-traceable pseudovirus in the upper respiratory tract of male humanized ACE2 (hACE2) mice, organ-specific ACE2 dysfunction in acute period and the following ACE2 recovery in a relatively long period was visualized and quantified by ACE2 PET, revealing a complex pattern of virus concentration-dependent degree and time period-dependent tendency of ACE2 recovery, mainly a sudden decrease of apparent ACE2 in the heart, liver, kidneys, lungs, and so on, but the liver was of a quick functional compensation on ACE2 expression after a temporary decrease. ACE2 expression of most organs has recovered to a normal level at 15 days post inhalation, with brain and genitals still of a decreased SUVACE2 ; meanwhile, kidneys were of an increased SUVACE2 . These findings on ACE2 PET were further verified by western blot. When compared with high-resolution computed tomography on structural changes and FDG PET on glycometabolism, ACE2 PET was superior in an earlier diagnostic window during infection and more comprehensive understanding of functional dysfunction post-infection. In the respective ACE2 PET/CT and ACE2 PET/MR scans of a volunteer, the repeatability of SUVACE2 and the ACE2 specificity were further confirmed. In conclusion, [68] Ga-cyc-DX600 was developed as an ACE2-specific tracer, and the corresponding ACE2 PET revealed the dynamic patterns of functional ACE2 recovery and provided a reference and approach to explore the ACE2-related pathological basis of sequelae in long COVID.}, } @article {pmid36605094, year = {2022}, author = {Scharfenberg, D and Schild, AK and Warnke, C and Maier, F}, title = {A Network Perspective on Neuropsychiatric and Cognitive Symptoms of the Post-COVID Syndrome.}, journal = {Europe's journal of psychology}, volume = {18}, number = {4}, pages = {350-356}, pmid = {36605094}, issn = {1841-0413}, abstract = {Many patients that were infected with SARS-CoV-2 experience cognitive and affective symptoms weeks and months after their acute COVID-19 disease, even when acute symptoms were mild to moderate. For these patients, purely neurological explanations are struggling to explain the development and maintenance of the great variety of neuropsychiatric and cognitive symptoms occurring after COVID-19. We provide a psychological perspective based on the network theory of mental disorders as an added explanation that does not displace neurological mechanism but rather complements them. We suggest viewing the SARS-CoV-2 infection as a trigger that first activates nodes in a causally connected network of neuropsychiatric and cognitive symptoms. In the following, activation will spread throughout the network that will get in a self-sustaining stable and dysfunctional state manifesting in ongoing symptoms known as post-COVID-19 syndrome. The network perspective allows to generalize explanations for persistent neuropsychiatric and cognitive symptoms to patients that experienced mild or moderate acute courses of COVID-19, but also to similar phenomena following other viral infections. In addition, it could explain why some symptoms did not occur during acute COVID-19, but develop weeks or months after it. This network perspective shifts the focus from viewing persistent symptoms as a continuation of COVID-19 to acknowledging it as a complex syndrome that indeed originates from the disease but fully unfolds after it (post-COVID). To test the presented network perspective, we will need extensive cross-sectional as well as longitudinal data on cognitive and neuropsychiatric symptoms in post-COVID patients.}, } @article {pmid36603897, year = {2023}, author = {Twycross, A and Ceolta-Smith, J and Rayner, C}, title = {Abandoned by governments and employers.}, journal = {Evidence-based nursing}, volume = {26}, number = {1}, pages = {1-3}, doi = {10.1136/ebnurs-2022-103662}, pmid = {36603897}, issn = {1468-9618}, mesh = {Humans ; *Government ; }, } @article {pmid36601750, year = {2023}, author = {McWhirter, L and Carson, A}, title = {Functional cognitive disorders: clinical presentations and treatment approaches.}, journal = {Practical neurology}, volume = {23}, number = {2}, pages = {104-110}, doi = {10.1136/pn-2022-003608}, pmid = {36601750}, issn = {1474-7766}, mesh = {Humans ; *Cognition Disorders/diagnosis/etiology/therapy ; *Cognitive Dysfunction/diagnosis/therapy ; Cognition ; }, abstract = {Functional cognitive disorders (FCDs) are a common cause of subjective and mild cognitive impairment. Isolated FCDs commonly present to the cognitive clinic, but examination of the nature of the symptoms suggests that they can also be understood as a transdiagnostic feature of many other conditions. This article examines methods of formulating the cognitive difficulties in order to identify treatment targets in people with FCDs.}, } @article {pmid36601115, year = {2022}, author = {Bellan, M and Apostolo, D and Albè, A and Crevola, M and Errica, N and Ratano, G and Tonello, S and Minisini, R and D'Onghia, D and Baricich, A and Patrucco, F and Zeppegno, P and Gramaglia, C and Balbo, PE and Cappellano, G and Casella, S and Chiocchetti, A and Clivati, E and Giordano, M and Manfredi, M and Patti, G and Pinato, DJ and Puricelli, C and Raineri, D and Rolla, R and Sainaghi, PP and Pirisi, M and , }, title = {Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1038227}, pmid = {36601115}, issn = {1664-3224}, mesh = {Humans ; Adult ; Female ; *COVID-19 ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Interleukin-12 ; Cytokines ; Disease Progression ; }, abstract = {RATIONALE: Factors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called "long COVID") are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.

METHODS: A total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.

RESULTS: In 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.

CONCLUSIONS: Long COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.}, } @article {pmid36600580, year = {2023}, author = {McWhirter, L and Smyth, H and Hoeritzauer, I and Couturier, A and Stone, J and Carson, AJ}, title = {What is brain fog?.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {94}, number = {4}, pages = {321-325}, doi = {10.1136/jnnp-2022-329683}, pmid = {36600580}, issn = {1468-330X}, support = {/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Memory Disorders ; Fatigue ; Brain ; }, abstract = {BACKGROUND: The term 'brain fog' is increasingly used colloquially to describe difficulties in the cognitive realm. But what is brain fog? What sort of experiences do people talk about when they talk about brain fog? And, in turn, what might this tell us about potential underlying pathophysiological mechanisms? This study examined first-person descriptions in order to better understand the phenomenology of brain fog.

METHODS: Posts containing 'brain fog' were scraped from the social media platform Reddit, using python, over a week in October 2021. We examined descriptions of brain fog, themes of containing subreddits (topic-specific discussion forums), and causal attributions.

RESULTS: 1663 posts containing 'brain fog' were identified, 717 meeting inclusion criteria. 141 first person phenomenological descriptions depicted forgetfulness (51), difficulty concentrating (43), dissociative phenomena (34), cognitive 'slowness' and excessive effort (26), communication difficulties (22), 'fuzziness' or pressure (10) and fatigue (9). 50% (363/717) posts were in subreddits concerned with illness and disease: including COVID-19 (87), psychiatric, neurodevelopmental, autoimmune and functional disorders. 134 posts were in subreddits about drug use or discontinuation, and 44 in subreddits about abstention from masturbation. 570 posts included the poster's causal attribution, the most frequent attribution being long COVID in 60/570 (10%).

CONCLUSIONS: 'Brain fog' is used on Reddit to describe heterogeneous experiences, including of dissociation, fatigue, forgetfulness and excessive cognitive effort, and in association with a range of illnesses, drugs and behaviours. Encouraging detailed description of these experiences will help us better understand pathophysiological mechanisms underlying cognitive symptoms in health and disease.}, } @article {pmid36600349, year = {2022}, author = {Al-Oraibi, A and Naidu, JS and Chaka, A and Woolf, K and B Nellums, L and Tarrant, C and Pan, D and Sze, S and Martin, CA and Gogoi, M and Nazareth, J and Pareek, M}, title = {Prevalence of long COVID-19 among healthcare workers: a systematic review and meta-analysis protocol.}, journal = {BMJ open}, volume = {12}, number = {12}, pages = {e065234}, pmid = {36600349}, issn = {2044-6055}, support = {MR/V027549/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Health Personnel ; Meta-Analysis as Topic ; Systematic Reviews as Topic ; }, abstract = {INTRODUCTION: A proportion of those who survive the acute phase of COVID-19 experience prolonged symptoms, commonly known as long COVID-19. Given that healthcare workers (HCWs) face an elevated risk of acute COVID-19 compared with the general population, the global burden of long COVID-19 in HCWs is likely to be large; however, there is limited understanding of the prevalence of long COVID-19 in HCWs, or its symptoms and their clustering. This review will aim to estimate the pooled prevalence and the symptoms of long COVID-19 among HCWs infected with SARS-CoV-2 globally, and investigate differences by country, age, sex, ethnicity, vaccination status and occupation.

METHODS AND ANALYSIS: A systematic review and meta-analysis will be conducted. Medline (via Ovid), CINAHL (via EBSCO), Embase (via Ovid), PsycINFO (via EBSCO), OpenGrey (grey literature) and medRxiv (preprint server) will be searched from the 31 December 2019 onward. All research studies and preprint articles reporting any primary data on the prevalence and/or the symptoms of long COVID-19 among adult HCWs will be included. Methodological quality will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Outcomes are anticipated to be the prevalence of long COVID-19 among HCWs around the world and trajectory of symptoms. Data synthesis will include random-effect meta-analysis for studies reporting prevalence data of long COVID-19 following SARS-CoV-2 infection among HCWs. The results will be presented with a 95% CI as an estimated effect across studies. Heterogeneity will be assessed using I² statistic. Where meta-analysis is inappropriate, a narrative synthesis of the evidence will be conducted.

ETHICS AND DISSEMINATION: Ethical approval is not needed as data will be obtained from published articles. We will publish our findings in a peer-reviewed journal and disseminate the results of our review at conferences.

PROSPERO REGISTRATION NUMBER: CRD42022312781.}, } @article {pmid36599668, year = {2023}, author = {Buonsenso, D}, title = {Further evidence from a large US electronic health record-based study that some children and adolescents can develop postacute sequelae of SARS-CoV-2 infection.}, journal = {Evidence-based nursing}, volume = {26}, number = {3}, pages = {97}, doi = {10.1136/ebnurs-2022-103632}, pmid = {36599668}, issn = {1468-9618}, mesh = {Humans ; Adolescent ; Child ; *COVID-19 ; Electronic Health Records ; SARS-CoV-2 ; }, } @article {pmid36599625, year = {2023}, author = {Pinto Pereira, SM and Nugawela, MD and Rojas, NK and Shafran, R and McOwat, K and Simmons, R and Ford, T and Heyman, I and Ladhani, SN and Cheung, EY and Fox-Smith, L and Dalrymple, E and Stephenson, T}, title = {Post-COVID-19 condition at 6 months and COVID-19 vaccination in non-hospitalised children and young people.}, journal = {Archives of disease in childhood}, volume = {108}, number = {4}, pages = {289-295}, pmid = {36599625}, issn = {1468-2044}, support = {/DH_/Department of Health/United Kingdom ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Child ; Adolescent ; Infant ; *COVID-19/diagnosis/epidemiology/prevention & control ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Vaccination ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVES: To describe the physical and mental health of children and young people (CYP) 6 months after infection with SARS-CoV-2 and explore whether this varies by COVID-19 vaccination.

DESIGN: A non-hospitalised, national cohort of people aged 11-17 years old with PCR-confirmed SARS-CoV-2 infection and PCR negatives matched at study invitation, by age, sex, region and date of testing who completed questionnaires 6 months after PCR testing. The questionnaire included 21 symptoms and standardised scales (eg, EQ-5D-Y and Chalder Fatigue Scale).

RESULTS: 6407 test-positive and 6542 test-negative CYP completed the 6-month questionnaire: 60.9% of test-positive vs 43.2% of test-negative CYP reported at least one symptom 6 months post-test; 27.6% of test-positive vs 15.9% of test-negative CYP reported 3+ symptoms. Common symptoms at 6 months were tiredness and shortness of breath among both test-positive and test-negative CYP; however, the prevalence of both was higher in test-positive (38.4% and 22.8%, respectively) compared with test-negative CYP (26.7% and 10.9%, respectively). 24.5% test-positive vs 17.8% test-negative CYP met the Delphi research definition of long COVID. Mental health, well-being, fatigue and health-related quality of life scores were similar among test-positive and test-negative CYP 6 months post-test. Similarly, symptomatology was similar among COVID-19-vaccinated and COVID-19-unvaccinated test-positive and test-negative CYP.

CONCLUSIONS: Six-months post-PCR testing, CYP who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but test-positive CYP had higher symptom prevalence. Mental health, well-being, fatigue and health-related quality of life were similar among test-positive and test-negative CYP, and symptoms at 6 months were similar in COVID-19 vaccinated and unvaccinated.

TRIAL REGISTRATION NUMBER: ISRCTN 34804192.}, } @article {pmid36597543, year = {2022}, author = {Bramante, CT and Buse, JB and Liebovitz, D and Nicklas, J and Puskarich, MA and Cohen, K and Belani, H and Anderson, B and Huling, JD and Tignanelli, C and Thompson, J and Pullen, M and Siegel, L and Proper, J and Odde, DJ and Klatt, N and Sherwood, N and Lindberg, S and Wirtz, EL and Karger, A and Beckman, K and Erickson, S and Fenno, S and Hartman, K and Rose, M and Patel, B and Griffiths, G and Bhat, N and Murray, TA and Boulware, DR}, title = {Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36597543}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; K23 HL133604/HL/NHLBI NIH HHS/United States ; U54 CA210190/CA/NCI NIH HHS/United States ; P30 DK124723/DK/NIDDK NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Long Covid is an emerging chronic illness potentially affecting millions, sometimes preventing the ability to work or participate in normal daily activities. COVID-OUT was an investigator-initiated, multi-site, phase 3, randomized, quadruple-blinded placebo-controlled clinical trial (NCT04510194). The design simultaneously assessed three oral medications (metformin, ivermectin, fluvoxamine) using two by three parallel treatment factorial assignment to efficiently share placebo controls and assessed Long Covid outcomes for 10 months to understand whether early outpatient treatment of SARS-CoV-2 with metformin, ivermectin, or fluvoxamine prevents Long Covid.

METHODS: This was a decentralized, remotely delivered trial in the US of 1,125 adults age 30 to 85 with overweight or obesity, fewer than 7 days of symptoms, and enrolled within three days of a documented SARS-CoV-2 infection. Immediate release metformin titrated over 6 days to 1,500mg per day 14 days total; ivermectin 430mcg/kg/day for 3 days; fluvoxamine, 50mg on day one then 50mg twice daily through 14 days. Medical-provider diagnosis of Long Covid, reported by participant by day 300 after randomization was a pre-specified secondary outcome; the primary outcome of the trial was severe Covid by day 14.

RESULT: The median age was 45 years (IQR 37 to 54), 56% female of whom 7% were pregnant. Two percent identified as Native American; 3.7% as Asian; 7.4% as Black/African American; 82.8% as white; and 12.7% as Hispanic/Latino. The median BMI was 29.8 kg/m[2] (IQR 27 to 34); 51% had a BMI >30kg/m[2]. Overall, 8.4% reported having received a diagnosis of Long Covid from a medical provider: 6.3% in the metformin group and 10.6% in the metformin control; 8.0% in the ivermectin group and 8.1% in the ivermectin control; and 10.1% in the fluvoxamine group and 7.5% in the fluvoxamine control. The Hazard Ratio (HR) for Long Covid in the metformin group versus control was 0.58 (95% CI 0.38 to 0.88); 0.99 (95% CI 0.592 to 1.643) in the ivermectin group; and 1.36 in the fluvoxamine group (95% CI 0.785 to 2.385).

CONCLUSIONS: There was a 42% relative decrease in the incidence of Long Covid in the metformin group compared to its blinded control in a secondary outcome of this randomized phase 3 trial.}, } @article {pmid36597538, year = {2023}, author = {Prabhakaran, D and Day, GS and Munipalli, B and Rush, BK and Pudalov, L and Niazi, SK and Brennan, E and Powers, HR and Durvasula, R and Athreya, A and Blackmon, K}, title = {Neurophenotypes of COVID-19: risk factors and recovery outcomes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36597538}, issn = {2693-5015}, support = {K23 AG064029/AG/NIA NIH HHS/United States ; U01 AG057195/AG/NIA NIH HHS/United States ; U19 AG032438/AG/NIA NIH HHS/United States ; }, abstract = {Coronavirus disease 2019 (COVID-19) infection is associated with risk of persistent neurocognitive and neuropsychiatric complications, termed "long COVID". It is unclear whether the neuropsychological manifestations of COVID-19 present as a uniform syndrome or as distinct neurophenotypes with differing risk factors and recovery outcomes. We examined post-acute neuropsychological profiles following SARS-CoV-2 infection in 205 patients recruited from inpatient and outpatient populations, using an unsupervised machine learning cluster analysis, with objective and subjective measures as input features. This resulted in three distinct post-COVID clusters. In the largest cluster (69%), cognitive functions were within normal limits, although mild subjective attention and memory complaints were reported. Vaccination was associated with membership in this "normal cognition" phenotype. Cognitive impairment was present in the remaining 31% of the sample but clustered into two differentially impaired groups. In 16% of participants, memory deficits, slowed processing speed, and fatigue were predominant. Risk factors for membership in the "memory-speed impaired" neurophenotype included anosmia and more severe COVID-19 infection. In the remaining 15% of participants, executive dysfunction was predominant. Risk factors for membership in this milder "dysexecutive" neurophenotype included disease-nonspecific factors such as neighborhood deprivation and obesity. Recovery outcomes at 6-month follow-up differed across neurophenotypes, with the normal cognition group showing improvement in verbal memory and psychomotor speed, the dysexecutive group showing improvement in cognitive flexibility, and the memory-speed impaired group showing no objective improvement and relatively worse functional outcomes compared to the other two clusters. These results indicate that there are multiple post-acute neurophenotypes of long COVID, with different etiological pathways and recovery outcomes. This information may inform phenotype-specific approaches to treatment.}, } @article {pmid36597534, year = {2022}, author = {Lorman, V and Razzaghi, H and Song, X and Morse, K and Utidjian, L and Allen, AJ and Rao, S and Rogerson, C and Bennett, TD and Morizono, H and Eckrich, D and Jhaveri, R and Huang, Y and Ranade, D and Pajor, N and Lee, GM and Forrest, CB and Bailey, LC}, title = {A machine learning-based phenotype for long COVID in children: an EHR-based study from the RECOVER program.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36597534}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data.

METHODS AND FINDINGS: In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS-CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values.

CONCLUSIONS: The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses.

FUNDING SOURCE: This research was funded by the National Institutes of Health (NIH) Agreement OT2HL161847-01 as part of the Researching COVID to Enhance Recovery (RECOVER) program of research.

DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program, the NIH or other funders.}, } @article {pmid36597517, year = {2023}, author = {Berg, SK and Palm, P}, title = {Playing catch with long COVID - Understanding a new disease.}, journal = {The Lancet regional health. Europe}, volume = {25}, number = {}, pages = {100568}, pmid = {36597517}, issn = {2666-7762}, } @article {pmid36597293, year = {2022}, author = {Du, Y and Zhang, J and Wu, LJ and Zhang, Q and Wang, YX}, title = {The Epidemiology, Diagnosis and Prognosis of Long-COVID.}, journal = {Biomedical and environmental sciences : BES}, volume = {35}, number = {12}, pages = {1133-1139}, doi = {10.3967/bes2022.143}, pmid = {36597293}, issn = {2214-0190}, mesh = {Humans ; *COVID-19/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid36596904, year = {2023}, author = {Lui, DTW and Tsoi, KH and Lee, CH and Cheung, CYY and Fong, CHY and Lee, ACH and Tam, AR and Pang, P and Ho, TY and Law, CY and Lam, CW and To, KKW and Chow, WS and Woo, YC and Hung, IFN and Tan, KCB and Lam, KSL}, title = {A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors.}, journal = {Endocrine}, volume = {80}, number = {2}, pages = {380-391}, pmid = {36596904}, issn = {1559-0100}, mesh = {Male ; Humans ; Middle Aged ; Female ; Autoimmunity ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; Prospective Studies ; *COVID-19 ; SARS-CoV-2 ; *Thyroid Diseases ; Interferons ; Survivors ; }, abstract = {PURPOSE: We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID.

METHODS: We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month.

RESULTS: 250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence.

CONCLUSION: Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID.}, } @article {pmid36595621, year = {2024}, author = {Brickhouse, M and Gassen, J and Ryan, BJ and Muehlenbein, MP}, title = {Survey of COVID-19 isolation cases at a major university campus in the United States.}, journal = {Journal of American college health : J of ACH}, volume = {72}, number = {9}, pages = {3210-3215}, doi = {10.1080/07448481.2022.2155062}, pmid = {36595621}, issn = {1940-3208}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Universities/statistics & numerical data ; Male ; Female ; *Students/statistics & numerical data ; Young Adult ; Adult ; United States/epidemiology ; Surveys and Questionnaires ; SARS-CoV-2 ; Adolescent ; Quarantine ; }, abstract = {Objective: Baylor University established a surveillance system to assess the needs of students and faculty in isolation from SARS-CoV-2 as well as any longer-term symptoms. Participants: Overall, there were 309 responses between March 20 and May 19, 2021. Methods: A survey covering experience in isolation, symptoms, vaccination, and demographic characteristics was emailed to individuals on Day 7 of isolation; a follow-up health survey was sent 30 days later. Results: Only 9.6% of respondents reported needing assistance while in isolation. Nearly 75% of respondents experienced COVID-19 symptoms in isolation, and 31.9% had remaining symptoms after isolation. Older age, being male, and more severe symptoms were associated with longer symptom duration. Those vaccinated had lower odds of developing symptoms and having symptoms remaining post-isolation. Conclusions: The present study adds to our understanding of long-COVID in young adult populations, while providing a framework for similar institutions to sustain operations during a global pandemic.}, } @article {pmid36594004, year = {2023}, author = {Rhee, DK}, title = {COVID-19 infection and ginseng: Predictive influenza virus strains and non-predictive COVID-19 vaccine strains.}, journal = {Journal of ginseng research}, volume = {47}, number = {2}, pages = {347-348}, pmid = {36594004}, issn = {1226-8453}, abstract = {Vaccines help protect people from infections. However, Coronavirus 2019 (COVID-19) vaccinees often still become infected with COVID-19 variants (breakthrough infections) and may go on to suffer from long COVID symptoms due to short-lasting immunity and less-effective protection provided by available vaccines. Moreover, the current COVID-19 vaccines do not prevent viral transmission and ward off only about 15% of breakthrough infections. To prepare more effective vaccines, it is essential to predict the viral strains that will be circulating based on available epidemiological data. The World Health Organization recommends in advance which influenza strains are expected to be prevalent during influenza season to guide the production of influenza vaccines by pharmaceutical companies. However, future emerging COVID-19 strain(s) have not been possible to predict since no sound epidemiological information has been established. Thus, for more effective protection, immune stimulators alone or in combination with vaccines would be preferable to protect people from COVID-19 infection. One of those remedies would be ginseng, which has been used for potentiating immunity in the past.}, } @article {pmid36591299, year = {2022}, author = {Elizalde-Díaz, JP and Miranda-Narváez, CL and Martínez-Lazcano, JC and Martínez-Martínez, E}, title = {The relationship between chronic immune response and neurodegenerative damage in long COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1039427}, pmid = {36591299}, issn = {1664-3224}, mesh = {Humans ; Chemokines ; COVID-19 ; Immunity ; Interferon-alpha ; Interleukin-6 ; Ligands ; *Post-Acute COVID-19 Syndrome/complications/immunology/physiopathology ; SARS-CoV-2 ; *Neurodegenerative Diseases/etiology/immunology/physiopathology ; }, abstract = {In the past two years, the world has faced the pandemic caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which by August of 2022 has infected around 619 million people and caused the death of 6.55 million individuals globally. Although SARS-CoV-2 mainly affects the respiratory tract level, there are several reports, indicating that other organs such as the heart, kidney, pancreas, and brain can also be damaged. A characteristic observed in blood serum samples of patients suffering COVID-19 disease in moderate and severe stages, is a significant increase in proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-18 (IL-18), as well as the presence of autoantibodies against interferon-α (IFN-α), interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC motif chemokine ligand 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), and C-C motif chemokine ligand 1 (CCL1). Interestingly, it has been described that the chronic cytokinemia is related to alterations of blood-brain barrier (BBB) permeability and induction of neurotoxicity. Furthermore, the generation of autoantibodies affects processes such as neurogenesis, neuronal repair, chemotaxis and the optimal microglia function. These observations support the notion that COVID-19 patients who survived the disease present neurological sequelae and neuropsychiatric disorders. The goal of this review is to explore the relationship between inflammatory and humoral immune markers and the major neurological damage manifested in post-COVID-19 patients.}, } @article {pmid36591237, year = {2022}, author = {Dean, LS and Devendra, G and Jiyarom, B and Subia, N and Tallquist, MD and Nerurkar, VR and Chang, SP and Chow, DC and Shikuma, CM and Park, J}, title = {Phenotypic alteration of low-density granulocytes in people with pulmonary post-acute sequalae of SARS-CoV-2 infection.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1076724}, pmid = {36591237}, issn = {1664-3224}, support = {P30 GM114737/GM/NIGMS NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; K12 HL143960/HL/NHLBI NIH HHS/United States ; R01 HL144067/HL/NHLBI NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; R21 HL156112/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Cohort Studies ; *COVID-19/metabolism ; SARS-CoV-2 ; Granulocytes/metabolism ; Phenotype ; }, abstract = {BACKGROUND: Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored.

METHODS: Using participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry.

RESULTS: The number of LDGs was elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10[+] and CD16[hi] subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from COVID-19 convalescents (PPASC and NRS) displayed increased markers of NET forming ability and aggregation with platelets compared to LDGs from NP, but no differences were observed between PPASC and NRS.

CONCLUSIONS: Our data from a small cohort study demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in COVID-19 convalescent individuals may be associated with PPASC prognosis and development.}, } @article {pmid36589958, year = {2022}, author = {Pagen, DME and van Bilsen, CJA and Brinkhues, S and Moonen, CPB and Van Herck, M and Konings, K and den Heijer, CDJ and Mujakovic, S and Ter Waarbeek, HLG and Bouwmeester-Vincken, N and Vaes, AW and Spruit, MA and Hoebe, CJPA and Dukers-Muijrers, NHTM}, title = {Design and recruitment of a large-scale cohort study on prevalence, risk factors and impact evaluation of post-COVID-19 condition and its wider long-term social, mental, and physical health impact: The PRIME post-COVID study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1032955}, pmid = {36589958}, issn = {2296-2565}, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Retrospective Studies ; Prevalence ; Risk Factors ; }, abstract = {BACKGROUND: Persistent symptoms, described as long COVID or post-COVID-19 condition, pose a potential public health problem. Here, the design and recruitment of the PRIME post-COVID study is described. PRIME post-COVID is a large-scale population-based observational study that aims to improve understanding of the occurrence, risk factors, social, physical, mental, emotional, and socioeconomic impact of post-COVID-19 condition.

METHODS: An observational open cohort study was set up, with retrospective and prospective assessments on various health-conditions and health-factors (medical, demographic, social, and behavioral) based on a public health COVID-19 test and by self-report (using online questionnaires in Dutch language). Invited for participation were, as recorded in a public health registry, adults (18 years and older) who were tested for COVID-19 and had a valid Polymerase Chain Reaction (PCR) positive or negative test result, and email address. In November 2021, 61,655 individuals were invited by email to participate, these included all eligible adults who tested PCR positive between 1 June 2020 and 1 November 2021, and a sample of adults who tested negative (2:1), comparable in distribution of age, sex, municipality of residence and year-quarter of testing. New recruitment periods are planned as well. Participants are followed over time by regular follow-up measurements. Data are analyzed using the appropriate data-analyses methods.

DISCUSSION: The PRIME post-COVID study will provide insights into various health-related aspects of post-COVID-19 condition in the context of various stages of the COVID-19 pandemic. Results will inform practical guidance for society, clinical and public health practice for the prevention and care for long-term impact of COVID-19.

NCT05128695.}, } @article {pmid36589219, year = {2022}, author = {Liao, X and Guan, Y and Liao, Q and Ma, Z and Zhang, L and Dong, J and Lai, X and Zheng, G and Yang, S and Wang, C and Liao, Z and Song, S and Yi, H and Lu, H}, title = {Long-term sequelae of different COVID-19 variants: The original strain versus the Omicron variant.}, journal = {Global health & medicine}, volume = {4}, number = {6}, pages = {322-326}, pmid = {36589219}, issn = {2434-9194}, abstract = {Although Omicron appears to cause less severe acute illness than the original strain, the potential for large numbers of patients to experience long COVID is a major concern. Little is known about the recovery phase in cases of Omicron, highlighting the importance of dynamically monitor long COVID in those patients. Subjects of the current study were patients available for a three-month follow-up who were admitted from January 13 to May 22, 2020 (period of the original strain) and from January 1 to May 30, 2022 (period of Omicron). Twenty-eight-point-four percent of patients infected with the original strain had long-term symptoms of COVID-19 and 5.63% of those infected with the Omicron strain had such symptoms. The most common symptom was a cough (18.5%), followed by tightness in the chest (6.5%), in patients infected with the original strain. Fatigue (2.4%) and dyspnea (1.7%) were the most commonly reported symptoms in patients infected with the Omicron strain. The respiratory system is the primary target of SARSCoV-2. Supportive treatment is the basis for the treatment of respiratory symptoms in patients with COVID-19. Quality sleep and good nutrition may alleviate fatigue and mental issues. Further knowledge about a long-term syndrome due to Omicron needs to be discussed and assembled so that healthcare and workforce planners can rapidly obtain information to appropriately allocate resources.}, } @article {pmid36588926, year = {2022}, author = {Bhattacharyya, A and Seth, A and Rai, S}, title = {The effects of long COVID-19, its severity, and the need for immediate attention: Analysis of clinical trials and Twitter data.}, journal = {Frontiers in big data}, volume = {5}, number = {}, pages = {1051386}, pmid = {36588926}, issn = {2624-909X}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) has been declared a pandemic since March 2020 by the World Health Organization; identifying the disease progression, predicting patient outcomes early, the possibility of long-term adverse events through effective modeling, and the use of real-world data are of immense importance to effective treatment, resource allocation, and prevention of severe adverse events of grade 4 or 5.

METHODS: First, we raise awareness about the different clinical trials on long COVID-19. The trials were selected with the search term "long COVID-19" available in ClinicalTrials.gov. Second, we curated the recent tweets on long-haul COVID-19 and gave an overview of the sentiments of the people. The tweets obtained with the query term #long COVID-19 consisted of 8,436 tweets between 28 August 2022 and 06 September 2022. We utilized the National Research Council (NRC) Emotion Lexicon method for sentiment analysis. Finally, we analyze the retweet and favorite counts are associated with the sentiments of the tweeters via a negative binomial regression model.

RESULTS: Our results find that there are two types of clinical trials being conducted: observational and interventional. The retweet counts and favorite counts are associated with the sentiments and emotions, such as disgust, joy, sadness, surprise, trust, negative, and positive.

CONCLUSION: We need resources and further research in the area of long COVID-19.}, } @article {pmid36588333, year = {2022}, author = {Maiese, K}, title = {Apolipoprotein-ε4 allele (APOE-ε4) as a Mediator of Cognitive Loss and Dementia in Long COVID-19.}, journal = {Current neurovascular research}, volume = {19}, number = {5}, pages = {435-439}, doi = {10.2174/156720261905221227114624}, pmid = {36588333}, issn = {1875-5739}, } @article {pmid36587841, year = {2023}, author = {Jassat, W and Mudara, C and Vika, C and Welch, R and Arendse, T and Dryden, M and Blumberg, L and Mayet, N and Tempia, S and Parker, A and Nel, J and Perumal, R and Groome, MJ and Conradie, F and Ndjeka, N and Sigfrid, L and Merson, L and Cohen, C}, title = {A cohort study of post-COVID-19 condition across the Beta, Delta, and Omicron waves in South Africa: 6-month follow-up of hospitalized and nonhospitalized participants.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {128}, number = {}, pages = {102-111}, pmid = {36587841}, issn = {1878-3511}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Humans ; Female ; Cohort Studies ; South Africa ; Prospective Studies ; Follow-Up Studies ; Quality of Life ; *COVID-19 ; *HIV Infections ; }, abstract = {OBJECTIVES: The study aimed to describe the prevalence of and risk factors for post-COVID-19 condition (PCC).

METHODS: This was a prospective, longitudinal observational cohort study. Hospitalized and nonhospitalized adults were randomly selected to undergo telephone assessment at 1, 3, and 6 months. Participants were assessed using a standardized questionnaire for the evaluation of symptoms and health-related quality of life. We used negative binomial regression models to determine factors associated with the presence of ≥1 symptoms at 6 months.

RESULTS: A total of 46.7% of hospitalized and 18.5% of nonhospitalized participants experienced ≥1 symptoms at 6 months (P ≤0.001). Among hospitalized people living with HIV, 40.4% had persistent symptoms compared with 47.1% among participants without HIV (P = 0.108). The risk factors for PCC included older age, female sex, non-Black race, presence of a comorbidity, greater number of acute COVID-19 symptoms, hospitalization/COVID-19 severity, and wave period (lower risk of persistent symptoms for the Omicron compared with the Beta wave). There were no associations between self-reported vaccination status with persistent symptoms.

CONCLUSION: The study revealed a high prevalence of persistent symptoms among South African participants at 6 months but decreased risk for PCC among participants infected during the Omicron BA.1 wave. These findings have serious implications for countries with resource-constrained health care systems.}, } @article {pmid36586593, year = {2023}, author = {Miskowiak, KW and Pedersen, JK and Gunnarsson, DV and Roikjer, TK and Podlekareva, D and Hansen, H and Dall, CH and Johnsen, S}, title = {Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life.}, journal = {Journal of affective disorders}, volume = {324}, number = {}, pages = {162-169}, pmid = {36586593}, issn = {1573-2517}, mesh = {Humans ; Female ; *Cognition Disorders/psychology ; Quality of Life ; Post-Acute COVID-19 Syndrome ; Prevalence ; Cross-Sectional Studies ; *COVID-19/epidemiology ; *Cognitive Dysfunction/etiology/complications ; Cognition ; Patient Acuity ; Neuropsychological Tests ; }, abstract = {BACKGROUND: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner.

METHODS: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients' cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education.

RESULTS: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life.

LIMITATIONS: The study was cross-sectional, which precludes causality inferences.

CONCLUSIONS: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.}, } @article {pmid36584771, year = {2023}, author = {Fernández-de-Las-Peñas, C and Arendt-Nielsen, L and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Palomar-Gallego, MA and Pellicer-Valero, OJ and Giordano, R}, title = {ACE1 rs1799752 polymorphism is not associated with long-COVID symptomatology in previously hospitalized COVID-19 survivors.}, journal = {The Journal of infection}, volume = {86}, number = {3}, pages = {e67-e69}, pmid = {36584771}, issn = {1532-2742}, mesh = {Humans ; COVID-19/genetics ; Polymorphism, Genetic ; *Post-Acute COVID-19 Syndrome/genetics ; SARS-CoV-2 ; }, } @article {pmid36582565, year = {2022}, author = {Yousif, E and Premraj, S}, title = {A Review of Long COVID With a Special Focus on Its Cardiovascular Manifestations.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31933}, pmid = {36582565}, issn = {2168-8184}, abstract = {The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been the cause of the century's worst pandemic so far: coronavirus disease 2019 (COVID-19). It has led to unprecedented mortality and morbidity, resulting in devastating consequences worldwide. The acute manifestations of COVID-19 including respiratory as well as multisystem involvement have been causes of great concern among physicians. However, the long-term effects of the coronavirus have left many patients battling with chronic symptoms, ranging from extreme fatigue to cardiomyopathy. In this article, we review the chronic manifestations of COVID-19 with a focus on cardiovascular manifestations. We discuss the pathophysiology, post-acute sequelae, clinical manifestations, approach to the laboratory diagnosis of cardiovascular manifestations of long COVID, and a proposed multidisciplinary treatment method. We also explore the relationship between vaccination and the long COVID syndrome.}, } @article {pmid36582234, year = {2022}, author = {Haunhorst, S and Bloch, W and Javelle, F and Krüger, K and Baumgart, S and Drube, S and Lemhöfer, C and Reuken, P and Stallmach, A and Müller, M and Zielinski, CE and Pletz, MW and Gabriel, HHW and Puta, C}, title = {A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients - indications for their potential involvement in the development of Long COVID?.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1070994}, pmid = {36582234}, issn = {1664-3224}, mesh = {Humans ; CD4-Positive T-Lymphocytes ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; T-Lymphocytes, Regulatory ; }, abstract = {BACKGROUND: Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.

OBJECTIVE: The objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVID.

DESIGN: A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.

RESULTS: The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome's etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.

CONCLUSIONS: Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.}, } @article {pmid36580747, year = {2023}, author = {Jammoul, M and Naddour, J and Madi, A and Reslan, MA and Hatoum, F and Zeineddine, J and Abou-Kheir, W and Lawand, N}, title = {Investigating the possible mechanisms of autonomic dysfunction post-COVID-19.}, journal = {Autonomic neuroscience : basic & clinical}, volume = {245}, number = {}, pages = {103071}, pmid = {36580747}, issn = {1872-7484}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Autonomic Nervous System Diseases/etiology ; *Orthostatic Intolerance ; }, abstract = {Patients with long COVID suffer from many neurological manifestations that persist for 3 months following infection by SARS-CoV-2. Autonomic dysfunction (AD) or dysautonomia is one complication of long COVID that causes patients to experience fatigue, dizziness, syncope, dyspnea, orthostatic intolerance, nausea, vomiting, and heart palpitations. The pathophysiology behind AD onset post-COVID is largely unknown. As such, this review aims to highlight the potential mechanisms by which AD occurs in patients with long COVID. The first proposed mechanism includes the direct invasion of the hypothalamus or the medulla by SARS-CoV-2. Entry to these autonomic centers may occur through the neuronal or hematogenous routes. However, evidence so far indicates that neurological manifestations such as AD are caused indirectly. Another mechanism is autoimmunity whereby autoantibodies against different receptors and glycoproteins expressed on cellular membranes are produced. Additionally, persistent inflammation and hypoxia can work separately or together to promote sympathetic overactivation in a bidirectional interaction. Renin-angiotensin system imbalance can also drive AD in long COVID through the downregulation of relevant receptors and formation of autoantibodies. Understanding the pathophysiology of AD post-COVID-19 may help provide early diagnosis and better therapy for patients.}, } @article {pmid36580648, year = {2023}, author = {Barie, PS and Brindle, ME and Khadaroo, RG and Klassen, TL and Huston, JM}, title = {Omicron, Long-COVID, and the Safety of Elective Surgery for Adults and Children: Joint Guidance from the Therapeutics and Guidelines Committee of the Surgical Infection Society and the Surgery Strategic Clinical Network, Alberta Health Services.}, journal = {Surgical infections}, volume = {24}, number = {1}, pages = {6-18}, doi = {10.1089/sur.2022.274}, pmid = {36580648}, issn = {1557-8674}, mesh = {Adult ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; Alberta ; Multiple Organ Failure ; *COVID-19/epidemiology ; SARS-CoV-2 ; Health Services ; }, abstract = {Background: Active and recent coronavirus disease 2019 (COVID-19) infections are associated with morbidity and mortality after surgery in adults. Current recommendations suggest delaying elective surgery in survivors for four to 12 weeks, depending on initial illness severity. Recently, the predominant causes of COVID-19 are the highly transmissible/less virulent Omicron variant/subvariants. Moreover, increased survivability of primary infections has engendered the long-COVID syndrome, with protean manifestations that may persist for months. Considering the more than 600,000,000 COVID-19 survivors, surgeons will likely be consulted by recovered patients seeking elective operations. Knowledge gaps of the aftermath of Omicron infections raise questions whether extant guidance for timing of surgery still applies to adults or should apply to the pediatric population. Methods: Scoping review of relevant English-language literature. Results: Most supporting data derive from early in the pandemic when the Alpha variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predominated. The Omicron variant/subvariants generally cause milder infections with less organ dysfunction; many infections are asymptomatic, especially in children. Data are scant with respect to adult surgical outcomes after Omicron infection, and especially so for pediatric surgical outcomes at any stage of the pandemic. Conclusions: Numerous knowledge gaps persist with respect to the disease, the recovered pre-operative patient, the nature of the proposed procedure, and supporting data. For example, should the waiting period for all but urgent elective surgery be extended beyond 12 weeks, e.g., after serious/critical illness, or for patients with long-COVID and organ dysfunction? Conversely, can the waiting periods for asymptomatic patients or vaccinated patients be shortened? How shall children be risk-stratified, considering the distinctiveness of pediatric COVID-19 and the paucity of data? Forthcoming guidelines will hopefully answer these questions but may require ongoing modifications based on additional new data and the epidemiology of emerging strains.}, } @article {pmid36580406, year = {2024}, author = {Barker, KK and Whooley, O and Madden, EF and Ahrend, EE and Greene, RN}, title = {The long tail of COVID and the tale of long COVID: Diagnostic construction and the management of ignorance.}, journal = {Sociology of health & illness}, volume = {46}, number = {S1}, pages = {189-207}, pmid = {36580406}, issn = {1467-9566}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Sociology ; Uncertainty ; COVID-19 Testing ; }, abstract = {We bring together insights from the sociology of diagnosis and the sociology of ignorance to examine the early diagnostic unfolding of 'Long COVID' (LC). Originally described by patient activists, researchers set out to ponder its unwieldy clinical boundaries. Using a scoping review method in tandem with qualitative content analytic techniques, we analyse medicine's initial struggles to construct a LC diagnosis. Paying attention to the dynamics of ignorance, we highlight three consequential conceptual manoeuvres in the early classifications of LC: causal agnosticism concerning the relationship between COVID-19 and LC, evasion of lumping LC with similar conditions; and the predictable splitting off of medically explainable cases from the LC designation. These manoeuvres are not maleficent, inept or unreasonable. They are practical but impactful responses to the classificatory dilemmas present in the construction of diagnoses amidst ignorance. Although there are unique aspects to LC, we suggest that its early fate is nevertheless emblematic of medicine's diagnostic standardisation processes more generally. To varying degrees, diagnoses are ignorance management strategies; they create a pathway through the uncertainty at the core of disease realities. However, while diagnoses circumscribe some types of ignorance, they produce others through the creation of blind spots and paths not taken.}, } @article {pmid36579544, year = {2022}, author = {Jyonouchi, H and Geng, L and Rossignol, DA and Frye, RE}, title = {Long COVID Syndrome Presenting as Neuropsychiatric Exacerbations in Autism Spectrum Disorder: Insights for Treatment.}, journal = {Journal of personalized medicine}, volume = {12}, number = {11}, pages = {}, pmid = {36579544}, issn = {2075-4426}, support = {None//Jonty Foundation, St. Paul, MN/ ; None//The Brain Foundation, Pleasanton, CA./ ; }, abstract = {COVID-19 causes not only severe respiratory symptoms, but also long-term sequelae, even if the acute-phase symptoms are minor. Neurological and neuropsychiatric symptoms are emerging as major long-term sequalae. In patients with pre-existing behavioral symptoms, such as individuals with autism spectrum disorders (ASD), the emergence of neuropsychiatric symptoms due to long COVID can be difficult to diagnose and manage. Herein, we present three ASD cases who presented with markedly worsening neuropsychiatric symptoms following COVID-19 exposure and subsequent difficulty in managing the post-COVID neuropsychiatric symptoms. Case 1 contracted SARS-CoV-2 during the early stages of the pandemic and treatment targeting COVID-19-induced immune activation was delayed. Case 2 was asymptomatic in the acute stage of a confirmed COVID-19 exposure, but still developed significant neuropsychiatric symptoms. Case 3 demonstrated a difficult course, partly due to pre-existing immune dysregulation and prior use of multiple immunomodulating agents. In cases 1 and 3 for whom serial blood samples were obtained, notable changes in the production of inflammatory and counter-regulatory cytokines by peripheral blood monocytes were observed. The presented cases illustrate the profound effects of COVID-19 on neuropsychiatric symptoms in ASD subjects and the difficulty of managing long-COVID symptoms.}, } @article {pmid36579511, year = {2022}, author = {Sampogna, G and Di Vincenzo, M and Giallonardo, V and Perris, F and Volpicelli, A and Del Vecchio, V and Luciano, M and Fiorillo, A}, title = {The Psychiatric Consequences of Long-COVID: A Scoping Review.}, journal = {Journal of personalized medicine}, volume = {12}, number = {11}, pages = {}, pmid = {36579511}, issn = {2075-4426}, abstract = {The COVID-19 pandemic has represented a new form of traumatic event, affecting the general population worldwide and causing severe disruption of daily routine. A new urgent concern is related to the burden associated with COVID-19 symptoms that persist beyond the onset of infection, the so-called long-COVID syndrome. The present paper aims to: (1) describe the most frequent psychiatric symptoms reported by patients affected by long-COVID syndrome; (2) evaluate methodological discrepancies among the available studies; (3) inform clinicians and policy-makers on the possible strategies to be promoted in order to manage the psychiatric consequences of long-COVID syndrome. Twenty-one papers have been included in the present review, mostly with a cross-sectional or cohort design. Significant heterogeneity of long-COVID syndrome definitions was found. The presence of psychiatric symptoms was evaluated with very different assessment tools. The most common psychiatric symptoms of the long-COVID syndrome included fatigue, cognitive disturbances/impairment, depression, and anxiety symptoms. The rate of fatigue varied from 93.2-82.3% to 11.5%, cognitive impairment/cognitive dysfunction from 61.4% to 23.5% and depressive-anxiety symptoms from 23.5%to 9.5%.}, } @article {pmid36579288, year = {2022}, author = {Mehfooz, S and Mehrotra, N and Usmani, T and Raj, V}, title = {Fatality Chooses Its Path Through the Orbit: A Study of Rhino-Orbito-Cerebral Mucormycosis as a Complication of COVID-19 Infection.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31822}, pmid = {36579288}, issn = {2168-8184}, abstract = {Introduction and aim Mucormycosis is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes and it mainly affects people who are immunocompromised, or patients already infected with other diseases. The dreaded mucormycosis infection has recently gained gross ill-repute for having claimed many lives in coronavirus disease (COVID-19) and/or post-COVID-19 patients. Hence a need was felt to study the development of mucormycosis in COVID-19 patients to better prevent and treat this fungal infection in anticipated future waves of the pandemic. This study also aims to establish an association between COVID-19 positivity, systemic comorbidities, and treatment modalities with the possibility of occurrence of vision and life-threatening mucor infection of the nose, paranasal sinuses, orbit, and brain. Methods This is a hospital-based, retrospective, case-control study. The study reviewed case files of all patients diagnosed with rhino-orbito-cerebral mucormycosis (ROCM) from April 1, 2021, to May 31, 2021. A set of age-matched COVID-19-positive patients hospitalized during the study period with moderate to severe disease were recruited as controls. We addressed factors that could be associated with the development of fungal infection and studied the period between COVID-19 positivity and the onset of ROCM. Results The age of patients in both groups ranged from 40-60 years with 13 females and 17 males. A statistically significant correlation (p-value = 0.032) was found between positive reverse transcription-polymerase chain reaction (RT-PCR) history and use of intravenous (IV) corticosteroids (11 [73.3%] cases and all controls). The mean duration from COVID-19 positivity to the presentation of mucormycosis was 12.10±7.27 days. Uncontrolled blood sugar was found to be the most significant correlation (p-value = 0.003). Mucormycosis is 13.678 times more likely in people with abnormal hemoglobin A1c (HbA1c). Co-morbidities like anemia, chronic kidney disease (CKD), coronary artery disease (CAD), and leukemia were found in controls, but none of these conditions were seen in patients who developed mucormycosis. Conclusion Judicious use of steroids and strict control of blood sugar levels should be emphasized in the management of COVID-19 patients.}, } @article {pmid36577665, year = {2022}, author = {Kohn, L and Dauvrin, M and Detollenaere, J and Primus-de-Jong, C and Maertens de Noordhout, C and Castanares-Zapatero, D and Cleemput, I and Van den Heede, K}, title = {[Difficulties encountered by long COVID patients in the Belgian health system].}, journal = {Sante publique (Vandoeuvre-les-Nancy, France)}, volume = {34}, number = {5}, pages = {663-673}, doi = {10.3917/spub.225.0663}, pmid = {36577665}, issn = {0995-3914}, mesh = {Humans ; Belgium ; *COVID-19 ; Delivery of Health Care ; }, abstract = {INTRODUCTION: After contracting COVID-19, many people have continued to experience various symptoms for several weeks and months, even after a mild acute phase. These people with ‘long COVID’ faced difficulties when confronted with the healthcare system.

PURPOSE OF RESEARCH: In order to better understand their experience, we supplemented the information obtained in an online survey with a mixed qualitative approach based on 33 individual interviews and discussions with 101 participants in a forum in March 2021.

RESULTS: Several shortcomings were identified in the contacts of ‘long’ COVID patients with the health care system, such as the lack of listening or empathy of some health care professionals, the lack of a systematic or proactive approach during the diagnostic assessment, or the lack of interdisciplinary coordination. Patients feel misunderstood and are forced to develop their own strategies, whether for diagnosis or treatment. Patients’ discomfort has led them to question the value of medicine and to resort to unconventional therapies to alleviate their symptoms, sometimes at great cost.

CONCLUSIONS: Better informing the medical profession about the manifestation of the disease and the possible treatments, including the possibilities of reimbursement, would raise awareness and give them the tools to respond to the needs of ‘ long’ COVID patients. A comprehensive assessment of the patient through an “interdisciplinary assessment” seems necessary.}, } @article {pmid36575843, year = {2022}, author = {Melrose, J and Smith, MM}, title = {Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {14}, number = {4}, pages = {27}, doi = {10.31083/j.fbe1404027}, pmid = {36575843}, issn = {1945-0508}, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Flavonoids/therapeutic use/pharmacology ; Post-Acute COVID-19 Syndrome ; Molecular Docking Simulation ; Antiviral Agents/therapeutic use/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; *Neurodegenerative Diseases/drug therapy ; *Cognitive Dysfunction/drug therapy ; }, abstract = {The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.}, } @article {pmid36575774, year = {2023}, author = {Afroze, F and Arafat, SM and Ahmed, CM and Alam, B and Banu, S and Islam, MZ and Mahfuz, M and Parvin, I and Ackhter, MM and Shormi, I and Islam, F and Sultana, M and Chowdhury, AN and Ur Rahaman, MF and Khan, AH and Hasan, MN and Ahmed, S and Chisti, MJ and Ahmed, T}, title = {Features and risk factors of post-COVID-19 syndrome: findings from a longitudinal study in Bangladesh.}, journal = {The Lancet regional health. Southeast Asia}, volume = {11}, number = {}, pages = {100134}, pmid = {36575774}, issn = {2772-3682}, abstract = {BACKGROUND: A comprehensive study of the post-COVID syndrome (PCS) remains scarce in low-and middle-income countries. We assessed the prevalence, incidence rate, evolution over time, and risk factors of PCS among hospitalized (HS) and non-hospitalized (NHS) COVID-19 survivors.

METHODS: We undertook a prospective longitudinal study of COVID-19 survivors at months 1, 3, and 5 post-discharge or post-isolation period. The study was conducted at two COVID-19-designated hospitals in Dhaka, Bangladesh, between December 2020 and October 2021.

FINDINGS: 362 participants were enrolled in the study; the median time from the onset of COVID-19 to enrolment was 57 days (IQR 41, 82). At enrolment, after adjusting for potential confounders, the HS more often had one or more symptoms, peripheral neuropathy (PN), depression and anxiety disorder, poor quality of life, dyspnea, tachycardia, restrictive lung disease on spirometry, anemia, proteinuria, and need for insulin therapy than the non-hospitalized group (95% CI > 1 for all). Although most of these findings decreased significantly over time in HS, PN increased in both groups. The incidence of diabetes was 9.8/1000 person-month, and the new requirement of insulin therapy was higher (aOR, 6.71; 95% CI, 2.87, 15.67) among HS than the NHS. Older age, being female, comorbidity, cigarette smoking, hospitalization, and contact with COVID-19 cases were independently associated with PCS.

INTERPRETATION: We observed a high burden of PCS in hospitalized and non-hospitalized survivors despite most findings' decreasing trend over time. Our results underscore the importance of continuing long-term follow-up and subsequent management.

FUNDING: The United States Agency for International Development (USAID).}, } @article {pmid36575437, year = {2022}, author = {Naik, H and Shao, S and Tran, KC and Wong, AW and Russell, JA and Khor, E and Nacul, L and McKay, RJ and Carlsten, C and Ryerson, CJ and Levin, A}, title = {Evaluating fatigue in patients recovering from COVID-19: validation of the fatigue severity scale and single item screening questions.}, journal = {Health and quality of life outcomes}, volume = {20}, number = {1}, pages = {170}, pmid = {36575437}, issn = {1477-7525}, mesh = {Humans ; *Quality of Life ; Reproducibility of Results ; Severity of Illness Index ; *COVID-19/complications ; SARS-CoV-2 ; Surveys and Questionnaires ; Psychometrics ; }, abstract = {BACKGROUND: Fatigue is a common symptom in hospitalized and non-hospitalized patients recovering from COVID-19, but no fatigue measurement scales or questions have been validated in these populations. The objective of this study was to perform validity assessments of the fatigue severity scale (FSS) and two single-item screening questions (SISQs) for fatigue in patients recovering from COVID-19.

METHODS: We examined patients ≥ 28 days after their first SARS-CoV-2 infection who were hospitalized for their acute illness, as well as non-hospitalized patients referred for persistent symptoms. Patients completed questionnaires through 1 of 4 Post COVID-19 Recovery Clinics in British Columbia, Canada. Construct validity was assessed by comparing FSS scores to quality of life and depression measures. Two SISQs were evaluated based on the ability to classify fatigue (FSS score ≥ 4).

RESULTS: Questionnaires were returned in 548 hospitalized and 546 non-hospitalized patients, with scores computable in 96.4% and 98.2% of patients respectively. Cronbach's alpha was 0.96 in both groups. The mean ± SD FSS score was 4.4 ± 1.8 in the hospitalized and 5.2 ± 1.6 in the non-hospitalized group, with 62.5% hospitalized and 78.9% non-hospitalized patients classified as fatigued. Ceiling effects were 7.6% in the hospitalized and 16.1% in non-hospitalized patients. FSS scores negatively correlated with EQ-5D scores in both groups (Spearman's rho - 0.6 in both hospitalized and non-hospitalized; p < 0.001) and were higher among patients with a positive PHQ-2 depression screen (5.4 vs. 4.0 in hospitalized and 5.9 vs. 4.9 in non-hospitalized; p < 0.001). An SISQ asking whether there was "fatigue present" had a sensitivity of 70.6% in hospitalized and 83.2% in non-hospitalized patients; the "always feeling tired" SISQ, had a sensitivity of 70.5% and 89.6% respectively.

CONCLUSIONS: Fatigue was common and severe in patients referred for post COVID-19 assessment. Overall, the FSS is suitable for measuring fatigue in these patients, as there was excellent data quality, strong internal consistency, and construct validity. However, ceiling effects may be a limitation in the non-hospitalized group. SISQs had good sensitivity for identifying clinically relevant fatigue in non-hospitalized patients but only moderate sensitivity in the hospitalized group, indicating that there were more false negatives.}, } @article {pmid36575228, year = {2023}, author = {Matsumoto, C and Shibata, S and Kishi, T and Morimoto, S and Mogi, M and Yamamoto, K and Kobayashi, K and Tanaka, M and Asayama, K and Yamamoto, E and Nakagami, H and Hoshide, S and Mukoyama, M and Kario, K and Node, K and Rakugi, H}, title = {Long COVID and hypertension-related disorders: a report from the Japanese Society of Hypertension Project Team on COVID-19.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {3}, pages = {601-619}, pmid = {36575228}, issn = {1348-4214}, mesh = {Humans ; *COVID-19/complications ; *Hypertension ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) affects infected patients even after the acute phase and impairs their health and quality of life by causing a wide variety of symptoms, referred to as long COVID. Although the evidence is still insufficient, hypertension is suspected to be a potential risk factor for long COVID, and the occurrence of cardiovascular diseases seems to be a key facet of multiple conditions observed in long COVID. Nonetheless, there are few reports that comprehensively review the impacts of long COVID on hypertension and related disorders. As a sequel to our previous report in 2020 which reviewed the association of COVID-19 and hypertension, we summarize the possible influences of long COVID on hypertension-related organs, including the cardiovascular system, kidney, and endocrine system, as well as the pathophysiological mechanisms associated with the disorders in this review. Given that the clinical course of COVID-19 is highly affected by age and sex, we also review the impacts of these factors on long COVID. Lastly, we discuss areas of uncertainty and future directions, which may lead to better understanding and improved prognosis of clinical problems associated with COVID-19.}, } @article {pmid36575200, year = {2022}, author = {Imoto, W and Yamada, K and Kawai, R and Imai, T and Kawamoto, K and Uji, M and Kanda, H and Takada, M and Ohno, Y and Ohtani, H and Kono, M and Hikiishi, A and Eguchi, Y and Namikawa, H and Kawaguchi, T and Kakeya, H}, title = {A cross-sectional, multicenter survey of the prevalence and risk factors for Long COVID.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {22413}, pmid = {36575200}, issn = {2045-2322}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Sleep Initiation and Maintenance Disorders/complications ; Anosmia ; Dysgeusia ; Prevalence ; Risk Factors ; Chest Pain ; Dyspnea/epidemiology ; Fatigue/epidemiology/complications ; Alopecia/complications ; }, abstract = {Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.}, } @article {pmid36574210, year = {2023}, author = {Liao, B and Deng, YK and Zeng, M and Liu, Z}, title = {Long-term Consequences of COVID-19: Chemosensory Disorders.}, journal = {Current allergy and asthma reports}, volume = {23}, number = {2}, pages = {111-119}, pmid = {36574210}, issn = {1534-6315}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; *Olfaction Disorders/epidemiology/etiology/diagnosis ; Taste Disorders/epidemiology/etiology ; }, abstract = {PURPOSE OF REVIEW: A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies.

RECENT FINDINGS: Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3 months to 2 years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.}, } @article {pmid36573990, year = {2022}, author = {Suran, M}, title = {VA Finds Nirmatrelvir Associated With Lower Risk of Long COVID.}, journal = {JAMA}, volume = {328}, number = {24}, pages = {2386}, doi = {10.1001/jama.2022.20051}, pmid = {36573990}, issn = {1538-3598}, mesh = {Humans ; COVID-19/epidemiology/prevention & control ; *Post-Acute COVID-19 Syndrome/epidemiology/prevention & control ; Ritonavir ; *Viral Protease Inhibitors/therapeutic use ; United States Department of Veterans Affairs ; }, } @article {pmid36573989, year = {2022}, author = {Suran, M}, title = {HHS Releases New Report on Long COVID Experiences.}, journal = {JAMA}, volume = {328}, number = {24}, pages = {2386}, doi = {10.1001/jama.2022.20052}, pmid = {36573989}, issn = {1538-3598}, mesh = {Humans ; COVID-19 ; *Post-Acute COVID-19 Syndrome ; United States ; United States Dept. of Health and Human Services ; }, } @article {pmid36573390, year = {2022}, author = {Finsterer, J}, title = {Letter to the Editor: There Is No Indication for Treating Long COVID Vaccination Syndrome With Colchicine.}, journal = {Journal of Korean medical science}, volume = {37}, number = {50}, pages = {e357}, pmid = {36573390}, issn = {1598-6357}, mesh = {Adult ; Humans ; *Colchicine/therapeutic use ; *COVID-19/prevention & control ; Post-Acute COVID-19 Syndrome ; Vaccination ; RNA, Messenger ; }, } @article {pmid36573005, year = {2023}, author = {Spatz, ES and Gottlieb, M and Wisk, LE and Anderson, J and Chang, AM and Gentile, NL and Hill, MJ and Huebinger, RM and Idris, AH and Kinsman, J and Koo, K and Li, SX and McDonald, S and Plumb, ID and Rodriguez, RM and Saydah, S and Slovis, B and Stephens, KA and Unger, ER and Wang, RC and Yu, H and Hota, B and Elmore, JG and Weinstein, RA and Venkatesh, A}, title = {Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {9}, pages = {1559-1566}, pmid = {36573005}, issn = {1537-6591}, support = {75D30120C08008/IP/NCIRD CDC HHS/United States ; 75D30120C08008/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; *COVID-19/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; SARS-CoV-2 ; *Text Messaging ; }, abstract = {BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood.

METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email.

RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months.

CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID.

CLINICAL TRIALS REGISTRATION: NCT04610515.}, } @article {pmid36571092, year = {2023}, author = {Jadali, Z}, title = {COVID-19 and Auditory Dysfunctions: A Relatively Rare but Important Symptom.}, journal = {Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India}, volume = {75}, number = {2}, pages = {1321-1322}, pmid = {36571092}, issn = {2231-3796}, } @article {pmid36570972, year = {2022}, author = {Binka, M and Klaver, B and Cua, G and Wong, AW and Fibke, C and Velásquez García, HA and Adu, P and Levin, A and Mishra, S and Sander, B and Sbihi, H and Janjua, NZ}, title = {An Elastic Net Regression Model for Identifying Long COVID Patients Using Health Administrative Data: A Population-Based Study.}, journal = {Open forum infectious diseases}, volume = {9}, number = {12}, pages = {ofac640}, pmid = {36570972}, issn = {2328-8957}, abstract = {BACKGROUND: Long coronavirus disease (COVID) patients experience persistent symptoms after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Healthcare utilization data could provide critical information on the disease burden of long COVID for service planning; however, not all patients are diagnosed or assigned long COVID diagnostic codes. We developed an algorithm to identify individuals with long COVID using population-level health administrative data from British Columbia (BC), Canada.

METHODS: An elastic net penalized logistic regression model was developed to identify long COVID patients based on demographic characteristics, pre-existing conditions, COVID-19-related data, and all symptoms/conditions recorded >28-183 days after the COVID-19 symptom onset/reported (index) date of known long COVID patients (n = 2430) and a control group (n = 24 300), selected from all adult COVID-19 cases in BC with an index date on/before October 31, 2021 (n = 168 111). Known long COVID cases were diagnosed in a clinic and/or had the International Classification of Diseases, Tenth Revision, Canada (ICD-10-CA) code for "post COVID-19 condition" in their records.

RESULTS: The algorithm retained known symptoms/conditions associated with long COVID, demonstrating high sensitivity (86%), specificity (86%), and area under the receiver operator curve (93%). It identified 25 220 (18%) long COVID patients among the remaining 141 381 adult COVID-19 cases, >10 times the number of known cases. Known and predicted long COVID patients had comparable demographic and health-related characteristics.

CONCLUSIONS: Our algorithm identified long COVID patients with a high level of accuracy. This large cohort of long COVID patients will serve as a platform for robust assessments on the clinical course of long COVID, and provide much needed concrete information for decision-making.}, } @article {pmid36570827, year = {2022}, author = {Llana, T and Mendez, M and Zorzo, C and Fidalgo, C and Juan, MC and Mendez-Lopez, M}, title = {Anosmia in COVID-19 could be associated with long-term deficits in the consolidation of procedural and verbal declarative memories.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {1082811}, pmid = {36570827}, issn = {1662-4548}, abstract = {BACKGROUND AND PURPOSE: Long-COVID describes the long-term effects of the coronavirus disease 2019 (COVID-19). In long-COVID patients, neuropsychological alterations are frequently reported symptoms. Research points to medial temporal lobe dysfunction and its association with anosmia in long-COVID patients. This study aims to investigate the acquisition and consolidation of declarative and procedural memory in long-COVID patients and to explore whether anosmia is related to these dissociated memory functions.

METHODS: Forty-two long-COVID participants and 30 controls (C) were recruited. The sample of long-COVID patients was divided into two groups based on the presence or absence of anosmia, group A and group NA, respectively. Objective performance in verbal declarative memory (Paired-Associate Learning, PAL), procedural memory (Mirror Tracing Test, MTT), general cognitive function (Montreal Cognitive Assessment scale), psychomotor speed, and incidental learning (Digit Symbol Substitution Test) were assessed and compared among the A, NA, and C groups. Long-term retention of PAL and MTT were assessed 24 h after acquisition.

RESULTS: Lower scores in general cognition, psychomotor speed, and sustained attention were found in A and NA compared with C. However, incidental learning, both cue-guided and free-recalled, was diminished in group A compared with C, with no differences with group NA. General cognition and incidental learning were related to declarative memory function exclusively in long-COVID groups. Long-COVID groups presented lower long-term retention of verbal declarative memory than controls in recall tests but no differences in recognition tests. No group differences were found in the acquisition of procedural memory. However, long-term retention of this memory was worse in group A as compared to the NA and C groups, respectively, when errors and time of execution were considered.

CONCLUSION: Findings support that consolidation of both procedural and declarative memories is more affected than the acquisition of these memories in long-COVID patients, who are also more vulnerable to deficits in delayed recall than in recognition of declarative memories. Deficits in the consolidation of procedural memory and immediate recall of declarative information are especially relevant in long-COVID participants with anosmia. This indicates that anosmia in COVID-19 could be associated with a long-term dysfunction of the limbic system.}, } @article {pmid36570602, year = {2023}, author = {Halili, A}, title = {Temporal model for central sensitization: A hypothesis for mechanism and treatment using systemic manual therapy, a focused review.}, journal = {MethodsX}, volume = {10}, number = {}, pages = {101942}, pmid = {36570602}, issn = {2215-0161}, abstract = {The purpose of this focused review is to develop a consolidated hypothesis as to the causes and mechanisms of central sensitization and a related model for a treatment approach using Systemic Manual Therapy (SMT). The key to understanding central sensitization is a firm grasp on structure and function of the Locus-coeruleus noradrenaline system (LC-NA). This system uses an elaborate switching mechanism to control the level and rate of activation of multiple systems. This review evaluates the mechanisms and temporal relationships behind four components: salient stimuli, threat coding, aberrant afferent input, and oxidative stress. The five-stage temporal model for central sensitization includes phasic activation of the LC-NA system, salient stimuli, threat coding of salient stimuli, central sensitization, and neural degeneration. The three components of treatment include temporarily reducing afferent visceral input, shifting humoral inflammatory activity away from the brain and outside the body, and reducing oxidative stress by making oxygenated blood more available around the LC and other stressed areas in the brain. The SMT protocols that could help in reduction of visceral afferent input are GUOU, Barral and LAUG. Protocols that should shift humoral inflammatory activity away from the brain or completely out of the body include UD and DCS. One protocol that can potentially reduce oxidative stress by making oxygenated blood more available around the LC is CCCV. Future research and hypothesis-testing strategies as well as limitations are further discussed.}, } @article {pmid36570463, year = {2022}, author = {Zhang, J}, title = {Investigating neurological symptoms of infectious diseases like COVID-19 leading to a deeper understanding of neurodegenerative disorders such as Parkinson's disease.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {968193}, pmid = {36570463}, issn = {1664-2295}, abstract = {Apart from common respiratory symptoms, neurological symptoms are prevalent among patients with COVID-19. Research has shown that infection with SARS-CoV-2 accelerated alpha-synuclein aggregation, induced Lewy-body-like pathology, caused dopaminergic neuron senescence, and worsened symptoms in patients with Parkinson's disease (PD). In addition, SARS-CoV-2 infection can induce neuroinflammation and facilitate subsequent neurodegeneration in long COVID, and increase individual vulnerability to PD or parkinsonism. These findings suggest that a post-COVID-19 parkinsonism might follow the COVID-19 pandemic. In order to prevent a possible post-COVID-19 parkinsonism, this paper reviewed neurological symptoms and related findings of COVID-19 and related infectious diseases (influenza and prion disease) and neurodegenerative disorders (Alzheimer's disease, PD and amyotrophic lateral sclerosis), and discussed potential mechanisms underlying the neurological symptoms and the relationship between the infectious diseases and the neurodegenerative disorders, as well as the therapeutic and preventive implications in the neurodegenerative disorders. Infections with a relay of microbes (SARS-CoV-2, influenza A viruses, gut bacteria, etc.) and prion-like alpha-synuclein proteins over time may synergize to induce PD. Therefore, a systematic approach that targets these pathogens and the pathogen-induced neuroinflammation and neurodegeneration may provide cures for neurodegenerative disorders. Further, antiviral/antimicrobial drugs, vaccines, immunotherapies and new therapies (e.g., stem cell therapy) need to work together to treat, manage or prevent these disorders. As medical science and technology advances, it is anticipated that better vaccines for SARS-CoV-2 variants, new antiviral/antimicrobial drugs, effective immunotherapies (alpha-synuclein antibodies, vaccines for PD or parkinsonism, etc.), as well as new therapies will be developed and made available in the near future, which will help prevent a possible post-COVID-19 parkinsonism in the 21st century.}, } @article {pmid36569883, year = {2022}, author = {Yang, C and Zhao, H and Shannon, CP and Tebbutt, SJ}, title = {Omicron variants of SARS-CoV-2 and long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1061686}, pmid = {36569883}, issn = {1664-3224}, support = {177747//CIHR/Canada ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2/genetics ; *COVID-19 ; Public Health ; }, abstract = {Understanding the epidemiology of long COVID and emerging variants has significant public-health implications as physical interventions and restrictions that help limit viral spread are eased globally. Here, we provide rationales for the necessity of updating current vaccines to improve protection against omicron and emerging variants, as well as more research into understanding the epidemiology and mechanisms of long COVID.}, } @article {pmid36567371, year = {2023}, author = {Dağ Şeker, E and Erbahçeci Timur, İE}, title = {Assessment of early and long-COVID related retinal neurodegeneration with optical coherence tomography.}, journal = {International ophthalmology}, volume = {43}, number = {6}, pages = {2073-2081}, pmid = {36567371}, issn = {1573-2630}, mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retinal Ganglion Cells ; Post-Acute COVID-19 Syndrome ; Nerve Fibers ; *COVID-19/complications ; }, abstract = {PURPOSE: The aim of this study is to investigate short-term and long-term effects of coronovirus 19 disease (COVID-19) at inner and outer retinal layers of patients recovered from COVID-19 with Spectral Domain Optical Coherence Tomography (SD-OCT) and compare these to healthy subjects.

METHODS: Twenty-seven patients recovered from COVID-19, and age- and gender-matched 27 healthy controls were included in this study. Macular and peripapillary retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL) were analyzed with SD-OCT 1 month (V1 visit) and 12 months (V2 visit) after negative result of reverse transcriptase-polymerase chain reaction test.

RESULTS: Macular RNFL thickness in outer ring was thinner at V1 and V2 visits than healthy control (p = 0.049 and p = 0.005). Central and inferonasal quadrants of peripapillary RNFL thicknesses were reduced at V1 and V2 visits compared to controls (p = 0.001 and p = 0.024 for V1 visit; p = 0.001 and p = 0.006 for V2 visit). Thinning in ONL thickness in inner ring was observed at V1 and V2 visits than healthy subjects (p = 0.006 and p = 0.001).

CONCLUSION: Subclinical localized changes in macular and peripapillary RNFL and outer nuclear layer were demonstrated in early and 12-months follow-up after COVID-19 recovery.}, } @article {pmid36566815, year = {2023}, author = {Khan, N and Mahmud, N and Patel, M and Sundararajan, R and Reinisch, W}, title = {Incidence of Long COVID and Impact of Medications on the Risk of Developing Long COVID in a Nationwide Cohort of IBD Patients.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {21}, number = {7}, pages = {1960-1962.e1}, pmid = {36566815}, issn = {1542-7714}, support = {K08 DK124577/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Incidence ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Inflammatory Bowel Diseases/complications/drug therapy/epidemiology ; Risk Factors ; }, } @article {pmid36566741, year = {2023}, author = {Lenoir, A and Christe, A and Ebner, L and Beigelman-Aubry, C and Bridevaux, PO and Brutsche, M and Clarenbach, C and Erkosar, B and Garzoni, C and Geiser, T and Guler, SA and Heg, D and Lador, F and Mancinetti, M and Ott, SR and Piquilloud, L and Prella, M and Que, YA and von Garnier, C and Funke-Chambour, M}, title = {Pulmonary Recovery 12 Months after Non-Severe and Severe COVID-19: The Prospective Swiss COVID-19 Lung Study.}, journal = {Respiration; international review of thoracic diseases}, volume = {102}, number = {2}, pages = {120-133}, pmid = {36566741}, issn = {1423-0356}, mesh = {Humans ; Prospective Studies ; Switzerland/epidemiology ; *COVID-19 ; *Respiratory Insufficiency ; Lung/diagnostic imaging ; }, abstract = {BACKGROUND: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified.

OBJECTIVES: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19.

METHODS: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities.

RESULTS: At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased.

CONCLUSIONS: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.}, } @article {pmid36566073, year = {2023}, author = {Makoni, M}, title = {A long journey to long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {11}, number = {1}, pages = {21-22}, doi = {10.1016/S2213-2600(22)00499-4}, pmid = {36566073}, issn = {2213-2619}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36564007, year = {2023}, author = {da Fonseca Lima, EJ and Leite, RD}, title = {COVID-19 vaccination in children: a public health priority.}, journal = {Jornal de pediatria}, volume = {99 Suppl 1}, number = {Suppl 1}, pages = {S28-S36}, pmid = {36564007}, issn = {1678-4782}, mesh = {Vaccination ; *COVID-19 Vaccines ; Adolescent ; Systemic Inflammatory Response Syndrome ; Child ; Health Priorities ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology/prevention & control/complications ; }, abstract = {OBJECTIVE: Covid-19 had a direct impact on children's health. The aim of this review was to analyze epidemiological and clinical data, the consequences of the pandemic, and vaccination aspects in this group.

SOURCES OF DATA: The searches were carried out from January 2020 to November 2022, in the MEDLINE databases (PubMed) and publications of the Brazilian Ministry of Health and the Brazilian Society of Pediatrics.

SUMMARY OF FINDINGS: Covid-19 has a mild presentation in most children; however, the infection can progress to the severe form and, in some cases, to MIS-C. The prevalence of the so-called long Covid in children was 25.24%. Moreover, several indirect impacts occurred on the health of children and adolescents. Vaccination played a crucial role in enabling the reduction of severe disease and mortality rates. Children and adolescents, as a special population, were excluded from the initial clinical trials and, therefore, vaccination was introduced later in this group. Despite its importance, there have been difficulties in the efficient implementation of vaccination in the pediatric population. The CoronaVac vaccines are authorized in Brazil for children over three years of age and the pediatric presentations of the Pfizer vaccine have shown significant effectiveness and safety.

CONCLUSIONS: Covid-19 in the pediatric age group was responsible for the illness and deaths of a significant number of children. For successful immunization, major barriers have to be overcome. Real-world data on the safety and efficacy of several pediatric vaccines is emphasized, and the authors need a uniform message about the importance of immunization for all children.}, } @article {pmid36563487, year = {2023}, author = {Reese, JT and Blau, H and Casiraghi, E and Bergquist, T and Loomba, JJ and Callahan, TJ and Laraway, B and Antonescu, C and Coleman, B and Gargano, M and Wilkins, KJ and Cappelletti, L and Fontana, T and Ammar, N and Antony, B and Murali, TM and Caufield, JH and Karlebach, G and McMurry, JA and Williams, A and Moffitt, R and Banerjee, J and Solomonides, AE and Davis, H and Kostka, K and Valentini, G and Sahner, D and Chute, CG and Madlock-Brown, C and Haendel, MA and Robinson, PN and , and , }, title = {Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes.}, journal = {EBioMedicine}, volume = {87}, number = {}, pages = {104413}, pmid = {36563487}, issn = {2352-3964}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; KL2 TR003016/TR/NCATS NIH HHS/United States ; K01 AG070329/AG/NIA NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; R24 OD011883/OD/NIH HHS/United States ; U24 HG011449/HG/NHGRI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; RM1 HG010860/HG/NHGRI NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Disease Progression ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, long COVID is incompletely understood and characterised by a wide range of manifestations that are difficult to analyse computationally. Additionally, the generalisability of machine learning classification of COVID-19 clinical outcomes has rarely been tested.

METHODS: We present a method for computationally modelling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning.

FINDINGS: We found six clusters of PASC patients, each with distinct profiles of phenotypic abnormalities, including clusters with distinct pulmonary, neuropsychiatric, and cardiovascular abnormalities, and a cluster associated with broad, severe manifestations and increased mortality. There was significant association of cluster membership with a range of pre-existing conditions and measures of severity during acute COVID-19. We assigned new patients from other healthcare centres to clusters by maximum semantic similarity to the original patients, and showed that the clusters were generalisable across different hospital systems. The increased mortality rate originally identified in one cluster was consistently observed in patients assigned to that cluster in other hospital systems.

INTERPRETATION: Semantic phenotypic clustering provides a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.

FUNDING: NIH (TR002306/OT2HL161847-01/OD011883/HG010860), U.S.D.O.E. (DE-AC02-05CH11231), Donald A. Roux Family Fund at Jackson Laboratory, Marsico Family at CU Anschutz.}, } @article {pmid36562653, year = {2023}, author = {Bogusławski, S and Strzelak, A and Gajko, K and Peradzyńska, J and Popielska, J and Marczyńska, M and Kulus, M and Krenke, K}, title = {The outcomes of COVID-19 pneumonia in children-clinical, radiographic, and pulmonary function assessment.}, journal = {Pediatric pulmonology}, volume = {58}, number = {4}, pages = {1042-1050}, pmid = {36562653}, issn = {1099-0496}, mesh = {Humans ; Child ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; *COVID-19/complications ; Aftercare ; SARS-CoV-2 ; Patient Discharge ; Lung/diagnostic imaging ; Ultrasonography/methods ; }, abstract = {OBJECTIVES: The goal of this study was to assess the pulmonary sequelae of COVID-19 pneumonia in children.

STUDY DESIGN: Children (0-18 years old) diagnosed with COVID-19 pneumonia hospitalized between March 2020 and March 2021 were included in this observational study. All children underwent follow-up visits 3 months postdischarge, and if any abnormalities were stated, a second visit after the next 3 months was scheduled. Clinical assessment included medical history, physical examination, lung ultrasound (LUS) using a standardized protocol, and pulmonary function tests (PFTs). PFTs results were compared with healthy children.

RESULTS: Forty-one patients with COVID-19 pneumonia (severe disease n = 3, mechanical ventilation, n = 0) were included in the study. Persistent symptoms were reported by seven (17.1%) children, the most common was decreased exercise tolerance (57.1%), dyspnea (42.9%), and cough (42.9%). The most prevalent abnormalities in LUS were coalescent B-lines (37%) and small subpleural consolidations (29%). The extent of LUS abnormalities was significantly greater at the first than at the second follow-up visit (p = 0.03). There were no significant differences in PFTs results neither between the study group and healthy children nor between the two follow-up visits in the study group.

CONCLUSIONS: Our study shows that children might experience long-term sequelae following COVID-19 pneumonia. In the majority of cases, these are mild and resolve over time.}, } @article {pmid36561720, year = {2022}, author = {Alfadda, AA and Rafiullah, M and Alkhowaiter, M and Alotaibi, N and Alzahrani, M and Binkhamis, K and Siddiqui, K and Youssef, A and Altalhi, H and Almaghlouth, I and Alarifi, M and Albanyan, S and Alosaimi, MF and Isnani, A and Nawaz, SS and Alayed, K}, title = {Clinical and biochemical characteristics of people experiencing post-coronavirus disease 2019-related symptoms: A prospective follow-up investigation.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1067082}, pmid = {36561720}, issn = {2296-858X}, abstract = {BACKGROUND: Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics.

PURPOSE: To investigate the clinical and biochemical characteristics of people who recovered from COVID-19 after 6 months of discharge from the hospital.

METHODS: This was a prospective follow-up investigation of hospitalized and discharged COVID-19 patients. Adult patients admitted to King Saud University Medical City, Riyadh, Saudi Arabia, with laboratory-confirmed COVID-19 and discharged were recruited. The baseline demographic information, comorbidities, vital signs and symptoms, laboratory parameters, COVID-19 therapy, and outcomes were collected from the medical records. Blood samples were collected for cytokines estimation. A detailed interview about signs and symptoms was undertaken during the follow-up.

RESULTS: Half of the followed-up people reported experiencing at least one of the COVID-19-related symptoms. The mean blood pressure was found higher in follow-up. People with the symptoms were characterized by low lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without any post-COVID-19 symptoms. Cytokines IL-8, VEGF, and MCP-1 were higher in people with the most frequent symptoms.

CONCLUSION: People with post-COVID-19 symptoms were characterized by lower lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without symptoms. Individuals with the most frequent post-COVID-19 symptoms had higher baseline pro-inflammatory, chemotactic, and angiogenic cytokines.}, } @article {pmid36560907, year = {2023}, author = {Horikoshi, Y and Shibata, M and Funakoshi, H and Baba, S and Miyama, S}, title = {Post coronavirus disease 2019 condition in children at a children's hospital in Japan.}, journal = {Pediatrics international : official journal of the Japan Pediatric Society}, volume = {65}, number = {1}, pages = {e15458}, doi = {10.1111/ped.15458}, pmid = {36560907}, issn = {1442-200X}, mesh = {Female ; Humans ; Child ; *COVID-19/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; Japan/epidemiology ; Post-Acute COVID-19 Syndrome ; Dysgeusia ; Hospitals ; }, abstract = {BACKGROUND: Acute coronavirus disease 2019 (COVID-19) is associated with chronic symptoms. These have been termed the "post COVID-19 condition." The data on this condition in children are still limited. We therefore aimed to elucidate the characteristics of this post COVID-19 condition.

METHODS: Children referred to a long COVID-19 clinic were included at Tokyo Metropolitan Children's Medical Center between October 2021 and July 2022. Children with another diagnosis and those who failed to meet criteria for post COVID-19 condition were excluded. Demographic and clinical data were collected retrospectively.

RESULTS: Of 33 referrals, nine were excluded, and 24 fulfilled the criteria for post COVID-19 condition. The median age and percentage of girls were 12.5 (IQR: 11-13) years and 29.2%, respectively. All the patients had mild, acute COVID-19. Dysgeusia and brain fog was observed more frequently during the Delta and Omicron variant periods, respectively. School absenteeism >4 weeks was observed in 41.6% of the patients. Common symptoms included malaise, headache, dysgeusia, and dysosmia. The median duration of post COVID-19 condition was 4.5 (IQR: 2.8-5.2) months. Pain management and counseling using the pacing approach were the most commonly offered treatments. Symptom resolution and improvement was observed in 29.2% and 54.2% of the patients, respectively.

CONCLUSIONS: One third of the patients referred for long COVID did not fit the definition of the post COVID-19 condition. After a median follow up of 4.5 months, the majority of the cases resolved or improved.}, } @article {pmid36560801, year = {2022}, author = {Fernández-Lázaro, D and Santamaría, G and Sánchez-Serrano, N and Lantarón Caeiro, E and Seco-Calvo, J}, title = {Efficacy of Therapeutic Exercise in Reversing Decreased Strength, Impaired Respiratory Function, Decreased Physical Fitness, and Decreased Quality of Life Caused by the Post-COVID-19 Syndrome.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560801}, issn = {1999-4915}, mesh = {Humans ; Female ; Male ; *COVID-19/therapy ; Quality of Life ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Physical Fitness ; }, abstract = {In the current global scenario, many COVID-19 survivors present a severe deterioration in physical strength, respiratory function, and quality of life due to persistent symptoms and post-acute consequences of SARS-CoV-2 infection. These alterations are known as post-COVID-19 syndrome for which there is no specific and effective treatment for their management. Currently, therapeutic exercise strategies (ThEx) are effective in many diseases by reducing the appearance of complications and side effects linked to treatment, and are consequently of great relevance. In this study, we review the effect of ThEX in reversing decreased strength, impaired respiratory function, decreased physical fitness, and decreased quality of life (QoL) caused by post-COVID-19 syndrome. A literature search was conducted through the electronic databases, Medline (PubMed), SciELO and Cochrane Library Plus for this structured narrative review for studies published from database retrieval up till 12 December 2022. A total of 433 patients with post-COVID-19 syndrome condition (60% women) were included in the nine studies which met the inclusion/exclusion criteria. Overall, post-COVID-19 syndrome patients who followed a ThEx intervention showed improvements in strength, respiratory function, physical fitness and QoL, with no exercise-derived side effects. Thus, ThEx based on strength, aerobic and respiratory training could be an adjuvant non-pharmacological tool in the modulation of post-COVID-19 syndrome.}, } @article {pmid36560641, year = {2022}, author = {Ratcliffe, NA and Castro, HC and Gonzalez, MS and Mello, CB and Dyson, P}, title = {Reaching the Final Endgame for Constant Waves of COVID-19.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560641}, issn = {1999-4915}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Antiviral Agents/therapeutic use ; }, abstract = {Despite intramuscular vaccines saving millions of lives, constant devastating waves of SARS-CoV-2 infections continue. The elimination of COVID-19 is challenging, but necessary in order to avoid millions more people who would suffer from long COVID if we fail. Our paper describes rapidly advancing and innovative therapeutic strategies for the early stage of infection with COVID-19 so that tolerating continuing cycles of infection should be unnecessary in the future. These therapies include new vaccines with broader specificities, nasal therapies and antiviral drugs some targeting COVID-19 at the first stage of infection and preventing the virus entering the body in the first place. Our article describes the advantages and disadvantages of each of these therapeutic options which in various combinations could eventually prevent renewed waves of infection. Finally, important consideration is given to political, social and economic barriers that since 2020 hindered vaccine application and are likely to interfere again with any COVID-19 endgame.}, } @article {pmid36560633, year = {2022}, author = {Fernández-de-Las-Peñas, C and Notarte, KI and Peligro, PJ and Velasco, JV and Ocampo, MJ and Henry, BM and Arendt-Nielsen, L and Torres-Macho, J and Plaza-Manzano, G}, title = {Long-COVID Symptoms in Individuals Infected with Different SARS-CoV-2 Variants of Concern: A Systematic Review of the Literature.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560633}, issn = {1999-4915}, mesh = {Humans ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Databases, Factual ; }, abstract = {The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology.}, } @article {pmid36560392, year = {2022}, author = {Pourmasumi, S and Nazari, A and Ahmadi, Z and Kouni, SN and de Gregorio, C and Koniari, I and Dousdampanis, P and Mplani, V and Plotas, P and Assimakopoulos, S and Gogos, C and Aidonisdis, G and Roditis, P and Matsas, N and Velissaris, D and Calogiuri, G and Hung, MY and Altay, S and Kounis, NG}, title = {The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.}, journal = {Vaccines}, volume = {10}, number = {12}, pages = {}, pmid = {36560392}, issn = {2076-393X}, abstract = {Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.}, } @article {pmid36558963, year = {2022}, author = {Esposito, S and Autore, G and Argentiero, A and Ramundo, G and Perrone, S and Principi, N}, title = {Update on COVID-19 Therapy in Pediatric Age.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {12}, pages = {}, pmid = {36558963}, issn = {1424-8247}, abstract = {With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.}, } @article {pmid36558835, year = {2022}, author = {Rojas, K and Verdugo-Molinares, MG and Ochoa-Ruiz, AG and Canales, A and Reza-Zaldivar, EE and Limón-Rojas, A and Vallejo-Cardona, AA}, title = {Approximations to Diagnosis and Therapy of COVID-19 in Nervous Systems Using Extracellular Vesicles.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {12}, pages = {}, pmid = {36558835}, issn = {2076-0817}, abstract = {The SARS-CoV-2 virus was first identified at the end of December 2019, causing the disease known as COVID-19, which, due to the high degree of contagion, was declared a global pandemic as of 2020. The end of the isolation was in 2022, thanks to the global multidisciplinary work of the massive vaccination campaigns. Even with the current knowledge about this virus and the COVID-19 disease, there are many questions and challenges regarding diagnosis and therapy in the fight against this virus. One of the big problems is the so-called "long COVID", prolonged symptomatology characterized as a multiorgan disorder manifested as brain fog, fatigue, and shortness of breath, which persist chronically after the disease resolution. Therefore, this review proposes using extracellular vesicles (EVs) as a therapeutic or diagnostic option to confront the sequelae of the disease at the central nervous system level. Development: the review of updated knowledge about SARS-CoV-2 and COVID-19 is generally addressed as well as the current classification of extracellular vesicles and their proposed use in therapy and diagnosis. Through an analysis of examples, extracellular vesicles are highlighted to learn what happens in the central nervous system during and after COVID-19 and as a therapeutic option. Conclusions: even though there are limitations in the knowledge of the neurological manifestations of COVID-19, it is possible to observe the potential use of extracellular vesicles in therapy or as a diagnostic method and even the importance of their study for the knowledge of the pathophysiology of the disease.}, } @article {pmid36557705, year = {2022}, author = {Talotta, R}, title = {Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects?.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557705}, issn = {2076-2607}, abstract = {Long coronavirus disease-19 (COVID-19) is a newly discovered syndrome characterized by multiple organ manifestations that persist for weeks to months, following the recovery from acute disease. Occasionally, neurological and cardiovascular side effects mimicking long COVID-19 have been reported in recipients of COVID-19 vaccines. Hypothetically, the clinical similarity could be due to a shared pathogenic role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein produced by the virus or used for immunization. The S protein can bind to neuropilin (NRP)-1, which normally functions as a coreceptor for the vascular endothelial growth factor (VEGF)-A. By antagonizing the docking of VEGF-A to NRP-1, the S protein could disrupt physiological pathways involved in angiogenesis and nociception. One consequence could be the increase in unbound forms of VEGF-A that could bind to other receptors. SARS-CoV-2-infected individuals may exhibit increased plasma levels of VEGF-A during both acute illness and convalescence, which could be responsible for diffuse microvascular and neurological damage. A few studies suggest that serum VEGF-A may also be a potential biomarker for long COVID-19, whereas evidence for COVID-19 vaccines is lacking and merits further investigation.}, } @article {pmid36557244, year = {2022}, author = {Gil-Redondo, R and Conde, R and Bizkarguenaga, M and Bruzzone, C and Laín, A and González-Valle, B and Iriberri, M and Ramos-Acosta, C and Anguita, E and Arriaga Lariz, JI and España Yandiola, PP and Moran, MÁ and Jiménez-Mercado, ME and Egia-Mendikute, L and Seco, ML and Schäfer, H and Cannet, C and Spraul, M and Palazón, A and Embade, N and Lu, SC and Wist, J and Nicholson, JK and Mato, JM and Millet, O}, title = {An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study.}, journal = {Metabolites}, volume = {12}, number = {12}, pages = {}, pmid = {36557244}, issn = {2218-1989}, support = {//the SPRI I + D COVID-19 fund (Basque Government, bG-COVID-19)/ ; //BIOEF EITB Maratoia (BIO21/COV/037)/ ; //the European Research Council (ERC) (ERC-2018-StG 804236-NEXTGEN-IO), ISCiii DTS21/00094, RYC2018-024183-I; and PID2019-107956RA-I00/ ; //The Spinnaker Health Research Foundation, WA, The McCusker Foundation, WA, The Western Australian State Government/ ; //MRFF (grant number 2014349) for funding the Australian National Phenome Centre/ ; //the UK MRC/ ; //the Department of Jobs, Tourism, Science and Innovation, Government of Western Australian Premier's Fellowship/ ; //ARC Laureate Fellowship/ ; //Western Australian Covid Research Response team/ ; //Ministerio de Ciencia, Tecnología e Innovación (Minciencias), Ministerio de Educación Nacional, Ministerio de Industria, Comercio y Turismo e ICETEX (792-2017) 2a Convocatoria Ecosistema Científico - Colombia Científica para la Financiación de Proye/ ; //World Bank and Vicerrectoría de Investigaciones, Pontificia Universidad Javeriana, Bogotá, Co-lombia (contract no. FP44842 - 221-2018)/ ; }, abstract = {After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts.}, } @article {pmid36557009, year = {2022}, author = {Wirth, KJ and Löhn, M}, title = {Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {12}, pages = {}, pmid = {36557009}, issn = {1648-9144}, mesh = {Humans ; *Orthostatic Intolerance/complications/diagnosis ; Vasa Vasorum ; Microcirculation ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Autonomic Nervous System Diseases ; }, abstract = {Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection. The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID. We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels. We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability), also affects the vasa vasorum to impair the function of the capacitance vessels. In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.}, } @article {pmid36556998, year = {2022}, author = {Gutiérrez-Canales, LG and Muñoz-Corona, C and Barrera-Chávez, I and Viloria-Álvarez, C and Macías, AE and Guaní-Guerra, E}, title = {Quality of Life and Persistence of Symptoms in Outpatients after Recovery from COVID-19.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {12}, pages = {}, pmid = {36556998}, issn = {1648-9144}, mesh = {Humans ; Female ; *COVID-19/complications ; Quality of Life ; Outpatients ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {Background and Objectives: Patients infected with SARS-CoV-2 can have persistent symptoms after acute illness, which affects their quality of life (QoL). Research and data about this topic in Latin American ambulatory patients are scarce. Materials and Methods: We conducted an observational, prospective, transversal, and analytical study. To measure QoL, we used a validated Spanish version of the MOS/RAND 36-Item Short Form Health Survey (SF-36). Results: We included 206 outpatients in the study. A total of 73.3% patients had persistence of one or more symptoms. The most frequent persistent symptoms were fatigue (36.9%), anxiety (26.2%), and headache (24.8%). No statistically significant difference in the SF-36 QoL scores and the frequency of persistent COVID-19 symptoms was found when comparing the ≤5 and >5 months groups, except for myalgia, which was less frequently observed in the >5 months group after COVID-19 (26.2% vs. 14.1%, p < 0.038). Female gender was associated with an increased risk of persistence of symptoms (OR = 2.95, 95% CI 1.56−5.57). Having comorbidities/sequelae attributed to COVID-19 and persistence of COVID-19 symptoms were associated risk factors for poor physical component summary (PCS); on the other hand, female gender, anxiety, and depression were associated with poor mental component summary (MCS). Conclusion: Most outpatients had persistent COVID-19 symptoms after infection. Persistence of symptoms was associated with poor MCS and PCS. It is important to follow-up not only patients discharged from the hospital after SARS-CoV-2 infection, but also those under ambulatory management to provide them with rehabilitation and psychological therapy to improve their QoL.}, } @article {pmid36556422, year = {2022}, author = {Tofarides, AG and Christaki, E and Milionis, H and Nikolopoulos, GK}, title = {Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36556422}, issn = {2075-1729}, abstract = {Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden. In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition. Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition. Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination. Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.}, } @article {pmid36556290, year = {2022}, author = {Perrottelli, A and Sansone, N and Giordano, GM and Caporusso, E and Giuliani, L and Melillo, A and Pezzella, P and Bucci, P and Mucci, A and Galderisi, S}, title = {Cognitive Impairment after Post-Acute COVID-19 Infection: A Systematic Review of the Literature.}, journal = {Journal of personalized medicine}, volume = {12}, number = {12}, pages = {}, pmid = {36556290}, issn = {2075-4426}, abstract = {The present study aims to provide a critical overview of the literature on the relationships between post-acute COVID-19 infection and cognitive impairment, highlighting the limitations and confounding factors. A systematic search of articles published from 1 January 2020 to 1 July 2022 was performed in PubMed/Medline. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies using validated instruments for the assessment of cognitive impairment were included. Out of 5515 screened records, 72 studies met the inclusion criteria. The available evidence revealed the presence of impairment in executive functions, speed of processing, attention and memory in subjects recovered from COVID-19. However, several limitations of the literature reviewed should be highlighted: most studies were performed on small samples, not stratified by severity of disease and age, used as a cross-sectional or a short-term longitudinal design and provided a limited assessment of the different cognitive domains. Few studies investigated the neurobiological correlates of cognitive deficits in individuals recovered from COVID-19. Further studies with an adequate methodological design are needed for an in-depth characterization of cognitive impairment in individuals recovered from COVID-19.}, } @article {pmid36556137, year = {2022}, author = {Bernal-Utrera, C and Montero-Almagro, G and Anarte-Lazo, E and Gonzalez-Gerez, JJ and Rodriguez-Blanco, C and Saavedra-Hernandez, M}, title = {Therapeutic Exercise Interventions through Telerehabilitation in Patients with Post COVID-19 Symptoms: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556137}, issn = {2077-0383}, abstract = {The worldwide incidence of COVID-19 has generated a pandemic of sequelae. These sequelae require multidisciplinary rehabilitative work to address the multisystemic symptoms that patients will present with now and in the future. The aim of the present systematic review is to analyze the current situation of telerehabilitation in patients with COVID-19 sequelae and its effectiveness. Searches were conducted on the following databases: PubMed, Scopus, PEDro, and Web of Science (WOS). There was no complete homogeneity among the five selected articles, so we differentiated two clinical subgroups for the clustering of outcome measures: (group one) patients with post-discharge symptoms and (group two) patients with permanent symptoms or “long COVID-19” defined as persistent symptoms > 2 months. For group one, post-discharge sequelae, improvements were obtained in cardiovascular parameters, and physical test studies in group two presented very favorable results in all the cardiorespiratory measures and physical tests evaluated. Telerehabilitation through therapeutic exercise based on mixed protocols of aerobic, respiratory, and low-load strength exercises appear to be an effective and safe strategy for the recovery of short- and long-term post-COVID-19 sequelae.}, } @article {pmid36556030, year = {2022}, author = {Kalak, G and Jarjou'i, A and Bohadana, A and Wild, P and Rokach, A and Amiad, N and Abdelrahman, N and Arish, N and Chen-Shuali, C and Izbicki, G}, title = {Prevalence and Persistence of Symptoms in Adult COVID-19 Survivors 3 and 18 Months after Discharge from Hospital or Corona Hotels.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556030}, issn = {2077-0383}, abstract = {COVID-19 is characterized by persistent symptoms beyond acute illness. In this prospective cohort study of patients with COVID-19, we sought to characterize the prevalence and persistence of symptoms up to 18 months after diagnosis. We followed 166 patients and assessed their symptoms during acute illness, and at 3 and 18 months after disease onset. The mean number of symptoms per patient during acute disease was 2.3 (SD:1.2), dropping to 1.8 (SD:1.1) at 3 months after recovery and to 0.6 (SD:0.9) at 18 months after recovery. However, this decrease was not unidirectional. Between acute illness and 3 months, the frequency of symptoms decreased for cough (64.5%→24.7%), ageusia (21.7% to6%), anosmia (17.5%→5.4%), and generalized pain (10.8% to 5.4%) but increased for dyspnea (53%→57.2%) weakness (47%→54.8%), and brain fog (3%→8.4%). Between 3 and 18 months, the frequency of symptoms decreased for all symptoms but remained relatively high for dyspnea (15.8%), weakness (21.2%), and brain fog (7.3%). Symptoms may persist for at least 18 months after acute COVID-19 infection. During the medium- to long-term recovery period, the prevalence of some symptoms may decrease or remain stable, and the prevalence of others may increase before slowly decreasing thereafter. These data should be considered when planning post-acute care for these patients.}, } @article {pmid36556003, year = {2022}, author = {Frizzelli, A and Di Spigno, F and Moderato, L and Halasz, G and Aiello, M and Tzani, P and Manari, G and Calzetta, L and Pisi, R and Pelà, G and Piepoli, M and Chetta, A}, title = {An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36556003}, issn = {2077-0383}, abstract = {Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.}, } @article {pmid36555954, year = {2022}, author = {Agergaard, J and Ullahammer, WM and Gunst, JD and Østergaard, L and Schiøttz-Christensen, B}, title = {Characteristics of a Danish Post-COVID Cohort Referred for Examination due to Persistent Symptoms Six Months after Mild Acute COVID-19.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36555954}, issn = {2077-0383}, support = {NNF21OC0066984//Novo Nordisk Foundation/ ; A3770//Central Denmark Region/ ; }, abstract = {BACKGROUND: Post-COVID Clinics were recommended for patients with persistent symptoms following COVID-19, but no specific tests were suggested for evaluation. This study aimed to present a post-COVID clinic patient cohort and evaluate the use of a post-COVID symptom questionnaire (PCQ) score.

METHODS: Patients were referred from a population of approximately 1 million citizens. PCQ and standardized health scales were registered. Descriptive analyses were performed to assess the prevalence of symptoms, and correlation analyses was undertaken to asses convergent and discriminant trends between PCQ scores and health scales.

RESULTS: Of 547 patients, 447 accepted inclusion. The median age was 47 years and 12% of the patients were hospitalized. At a median of 6.3 (IQR 4.4-9.9) months after the onset of symptoms, 82% of the patients reported both physical exhaustion and concentration difficulties. Functional disability and extreme fatigue were reported as moderate to severe by 33% and 62% of the patients, respectively. The PCQ score correlated significantly with each of the standardized health scales.

CONCLUSION: Patients referred to a Post-COVID Clinic were previously generally healthy. At the time of diagnosis, they reported multiple symptoms with severely affected health. The PCQ score could be used as valid measure of Post-COVID severity.}, } @article {pmid36555948, year = {2022}, author = {Sunada, N and Nakano, Y and Otsuka, Y and Tokumasu, K and Honda, H and Sakurada, Y and Matsuda, Y and Hasegawa, T and Omura, D and Ochi, K and Hagiya, H and Ueda, K and Kataoka, H and Otsuka, F}, title = {Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36555948}, issn = {2077-0383}, abstract = {OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID.

METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed.

RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress.

CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.}, } @article {pmid36555931, year = {2022}, author = {Notarte, KI and de Oliveira, MHS and Peligro, PJ and Velasco, JV and Macaranas, I and Ver, AT and Pangilinan, FC and Pastrana, A and Goldrich, N and Kavteladze, D and Gellaco, MML and Liu, J and Lippi, G and Henry, BM and Fernández-de-Las-Peñas, C}, title = {Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {24}, pages = {}, pmid = {36555931}, issn = {2077-0383}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; }, abstract = {Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.}, } @article {pmid36554975, year = {2022}, author = {Reis, N and Dias, MJC and Sousa, L and Agostinho, I and Ricco, MT and Henriques, MA and Baixinho, CL}, title = {Telerehabilitation in the Transitional Care of Patients with Sequelae Associated with COVID-19: Perception of Portuguese Nurses.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {24}, pages = {}, pmid = {36554975}, issn = {1660-4601}, mesh = {Humans ; *Telerehabilitation ; *COVID-19 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Portugal ; *Transitional Care ; Disease Progression ; Perception ; *Nurses ; }, abstract = {The COVID-19 pandemic brought many changes and challenges to health professionals, due to a lack of knowledge when dealing with the disease, fear of contagion, and the sequelae that characterize long COVID. To deal with this situation, respiratory rehabilitation programs are recommended in face-to-face and/or telerehabilitation modalities. (1) Background: This study had as its primary aim identifying the aspects/components to be considered in the planning and implementation of telerehabilitation interventions that guarantee transitional care for people with long COVID-19 after hospitalization and as a secondary aim identifying the positive aspects of telerehabilitation. (2) Methods: The method used to answer the research question was a focus group, carried out online with eight nurses specialized in rehabilitation nursing. The answers to the semi-structured interview were subjected to content analysis, and qualitative data analysis software (WebQDA[®]) was used to organize and analyze the findings. (3) Results: Four categories emerged from the content analysis: coordination between care levels; transitional care telerehabilitation intervention; advantages of telerehabilitation; and opportunities. (4) Conclusions: These findings make an important contribution to the reorganization of transitional care, allowing the identification of central aspects to be considered in the planning and implementation of telerehabilitation programs for people with long COVID.}, } @article {pmid36554723, year = {2022}, author = {Goldhaber, NH and Kohn, JN and Ogan, WS and Sitapati, A and Longhurst, CA and Wang, A and Lee, S and Hong, S and Horton, LE}, title = {Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {24}, pages = {}, pmid = {36554723}, issn = {1660-4601}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Disease Progression ; Anxiety/epidemiology ; }, abstract = {Long COVID is a chronic condition characterized by symptoms such as fatigue, dyspnea, and cognitive impairment that persist or relapse months after an acute infection with the SARS-CoV-2 virus. Many distinct symptoms have been attributed to Long COVID; however, little is known about the potential clustering of these symptoms and risk factors that may predispose patients to certain clusters. In this study, an electronic survey was sent to patients in the UC San Diego Health (UCSDH) system who tested positive for COVID-19, querying if patients were experiencing symptoms consistent with Long COVID. Based on survey results, along with patient demographics reported in the electronic health record (EHR), linear and logistic regression models were used to examine putative risk factors, and exploratory factor analysis was performed to determine symptom clusters. Among 999 survey respondents, increased odds of Long COVID (n = 421; 42%) and greater Long COVID symptom burden were associated with female sex (OR = 1.73, 99% CI: 1.16-2.58; β = 0.48, 0.22-0.75), COVID-19 hospitalization (OR = 4.51, 2.50-8.43; β = 0.48, 0.17-0.78), and poorer pre-COVID self-rated health (OR = 0.75, 0.57-0.97; β = -0.19, -0.32--0.07). Over one-fifth of Long COVID patients screened positive for depression and/or anxiety, the latter of which was associated with younger age (OR = 0.96, 0.94-0.99). Factor analysis of 16 self-reported symptoms suggested five symptom clusters-gastrointestinal (GI), musculoskeletal (MSK), neurocognitive (NC), airway (AW), and cardiopulmonary (CP), with older age (β = 0.21, 0.11-0.30) and mixed race (β = 0.27, 0.04-0.51) being associated with greater MSK symptom burden. Greater NC symptom burden was associated with increased odds of depression (OR = 5.86, 2.71-13.8) and anxiety (OR = 2.83, 1.36-6.14). These results can inform clinicians in identifying patients at increased risk for Long COVID-related medical issues, particularly neurocognitive symptoms and symptom clusters, as well as informing health systems to manage operational expectations on a population-health level.}, } @article {pmid36554538, year = {2022}, author = {Blanco-Gonzalez, A and Cachón-Rodríguez, G and Del-Castillo-Feito, C and Cruz-Suarez, A}, title = {Is Purchase Behavior Different for Consumers with Long COVID?.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {24}, pages = {}, pmid = {36554538}, issn = {1660-4601}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Consumer Behavior ; Trust ; Uncertainty ; }, abstract = {COVID-19 has generated an uncertain environment, which has motivated changes in consumers' behavior globally. However, previous studies have not clarified if these effects are equally strong throughout the population. In this research, we want to analyze if there are behavioral differences between long-COVID consumers and others. For this purpose, we analyzed a sample of 522 consumers divided into three groups depending on their type of exposure to the disease: those with long COVID; ones that had recovered from COVID-19; and those that had never had COVID-19. The results show that the effect that COVID-19 has on purchase behavior differs depending on the type of exposure to the disease. In fact, those with long COVID experienced more pleasure when purchasing than other people, but they needed higher trust levels in the enterprises to purchase from them, since that reduces their perception of uncertainty. Furthermore, for long-COVID individuals, an organization's legitimacy level is even more important than for other consumer groups with less contact with the disease.}, } @article {pmid36554098, year = {2022}, author = {Kokolevich, ZM and Crowe, M and Mendez, D and Biros, E and Reznik, JE}, title = {Most Common Long COVID Physical Symptoms in Working Age Adults Who Experienced Mild COVID-19 Infection: A Scoping Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36554098}, issn = {2227-9032}, abstract = {BACKGROUND: One-third of patients who recover from COVID-19 present with long COVID. Their symptoms are broad, affecting their physical functioning and, ultimately, their quality of life. Many of those individuals who develop long COVID, possibly from a mild COVID-19 infection, are in the 18-65 age group. This prolongation of malaise directly influences national workforce economies.

OBJECTIVES: To summarise the commonly reported physical symptoms of long COVID in order to inform potential adjustments in healthcare for the employable population.

METHODS: The Embase, CINAHL, Medline, SCOPUS, and WHO COVID-19 databases were searched. The study selection process was based on the PRISMA guidelines. The extracted data were synthesised and presented narratively.

RESULTS: 7403 studies were accessed, comprising 60 cohort studies and 10 case series/studies, representing 289,213 patients who met our criteria. The most frequently reported physical symptoms were fatigue (92%), shortness of breath (SOB) (81.8%), muscle pain (43.6%), and joint pain (34.5%).

CONCLUSIONS: The range of reported physical symptoms was broad and varied; the main ones being fatigue, breathlessness/SOB, and pain. Similarities observed between long COVID and other post-acute infection syndromes may help formulate protocols to manage and promote recovery for long COVID patients. Inconsistencies were evident, particularly with a lack of adherence to the standardised definitions of long COVID.}, } @article {pmid36553942, year = {2022}, author = {Surapaneni, KM and Singhal, M and Saggu, SR and Bhatt, A and Shunmathy, P and Joshi, A}, title = {A Scoping Review on Long COVID-19: Physiological and Psychological Symptoms Post-Acute, Long-Post and Persistent Post COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36553942}, issn = {2227-9032}, abstract = {Background: The identification of persistent symptoms of chronic/long COVID-19 is crucial in understanding the management of long haulers of post COVID-19. Methods: Pub Med (Medline) database was scoped for original articles based on a search strategy related to the objectives. The selected articles post-screening were analyzed for variables relating to chronic/long COVID-19. Results were analyzed using descriptive statistics. Results: A total of 33 studies were reviewed. A total of 60% of the studies were observational studies and most of them were from high income countries. Almost half of the studies were in phase 3 of post-COVID-19, i.e., symptoms lasting >24 weeks. Among the physiological and psychological symptoms studied, fatigue, dyspnea, cough, headache, memory loss, depression, brain fog and lack of concentration were found to be the most frequently reported symptoms. Excessive sleep, constipation and neuropathic pain were among the least reported symptoms. Prior hospitalization, the female gender was found to be a risk factor. Limitations were reported by all studies. Conclusions: The major physiological and psychological symptoms of long COVID-19 have been explained with risk factors and its impact on patients’ lifestyles. The findings of this review hope to facilitate clinicians to draw conclusions to manage the long-term effects of post/chronic COVID-19.}, } @article {pmid36553888, year = {2022}, author = {Vásconez-González, J and Izquierdo-Condoy, JS and Fernandez-Naranjo, R and Ortiz-Prado, E}, title = {A Systematic Review and Quality Evaluation of Studies on Long-Term Sequelae of COVID-19.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {36553888}, issn = {2227-9032}, abstract = {COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being clarified. The aim of this study was to present an overview of the information available on the sequelae of COVID-19 in people who have suffered from the infection. A systematic review was carried out in which cohort studies, case series, and clinical case reports were included, and the PubMed, Scielo, SCOPUS, and Web of Science databases were extracted. Information was published from 2020 to 1 June 2022, and we included 26 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 8 for neurological and psychiatric, and 6 for cutaneous sequelae. Studies showed that the most common sequelae were those linked to the lungs, followed by skin, cutaneous, and psychiatric alterations. Women reported a higher incidence of the sequelae, as well as those with comorbidities and more severe COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its appearance, but it has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems, and further burden healthcare systems around the world.}, } @article {pmid36553195, year = {2022}, author = {Szoltysek-Boldys, I and Zielinska-Danch, W and Loboda, D and Wilczek, J and Gibinski, M and Paradowska-Nowakowska, E and Golba, KS and Sarecka-Hujar, B}, title = {Photoplethysmographic Measurement of Arterial Stiffness in Polish Patients with Long-COVID-19 Syndrome-The Results of a Cross-Sectional Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {36553195}, issn = {2075-4418}, support = {"Electrocardiology-Ochojec" Foundation//"Electrocardiology-Ochojec" Foundation/ ; }, abstract = {The coronavirus disease 2019 (COVID-19) is associated with an increase in the incidence of cardiovascular diseases (CVD) that persists even several months after the onset of infection. COVID-19 may also have an impact on arterial stiffness, which is a risk factor for CVD. We aimed to analyze if and to what extent arterial stiffness measured by photoplethysmography differed among COVID-19 convalescents depending on the acute phase severity and time elapsed since disease onset. A total of 225 patients (mean age 58.98 ± 8.57 years, 54.7% women) were analyzed after COVID-19 hospitalization at the Cardiac Rehabilitation Department of the Ustron Health Resort (Poland). In the entire study population, no differences were found in the mean values of stiffness index (SI) and reflection index (RI) depending on the severity of the acute COVID-19 and the time since the onset of the disease. There were no differences in the heart rate (HR) according to the severity of acute COVID-19; the mean HR was higher in patients who had COVID-19 less than 12 weeks before the study than in convalescents more than 24 weeks after the acute disease (p = 0.002). The mean values of SI and RI were higher in men than in women (p < 0.001), while the heart rate (HR) was similar in both sexes (p = 0.286). However, multiple linear regression analyses after adjusting for factors influencing arterial stiffness, i.e., sex, age, body mass index, smoking status, hypertension, diabetes, the severity of the acute COVID-19, and the time from the disease onset, confirmed that age, sex, time from disease onset, and diabetes are the most important determinants that could influence arterial stiffness.}, } @article {pmid36552013, year = {2022}, author = {Gryglewska-Wawrzak, K and Sakowicz, A and Banach, M and Maciejewski, M and Bielecka-Dabrowa, A}, title = {Factors of Persistent Limited Exercise Tolerance in Patients after COVID-19 with Normal Left Ventricular Ejection Fraction.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36552013}, issn = {2227-9059}, support = {PMMHRI-BCO.75/2020//Polish Mother's Memorial Hospital Research Institute/ ; }, abstract = {Exercise intolerance de novo is one of the most common reported symptoms in patients recovering from the Coronavirus Disease 2019 (COVID-19). The present study determines etiological and pathophysiological factors influencing the mechanism of impaired exercise tolerance in patients during Long-COVID. Consequently, the factors affecting the percentage predicted oxygen uptake at peak exercise (%VO2pred) in patients after COVID-19 with a normal left ventricular ejection fraction (LVEF) were assessment. A total of 120 patients recovering from COVID-19 at three to six months after confirmed diagnosis were included. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. The subjects were divided into the following groups: study patients’ group with worsen oxygen uptake (%VO2pred < 80%; n = 47) and control group presenting%VO2pred ≥ 80% (n = 73). ClinicalTrials.gov Identifier: NCT04828629. The male gender and the percent of total body water content (TBW%) were significantly higher in the study group compared to the control group (53 vs. 29%, p = 0.007 and 52.67 (±6.41) vs. 49.89 (±4.59), p = 0.02; respectively). Patients with %VO2pred < 80% presented significantly lower global peak systolic strain (GLPS), tricuspid annular plane systolic excursion (TAPSE), and late diastolic filling (A) velocity (19.34 (±1.72)% vs. 20.10 (±1.35)%, p = 0.03; 21.86 (±4.53) vs. 24.08 (±3.20) mm, p = 0.002 and median 59.5 (IQR: 50.0−71.0) vs. 70.5 (IQR: 62.0−80.0) cm/s, p = 0.004; respectively) compared to the controls. The results of the multiple logistic regression model show that (A) velocity (OR 0.40, 95%CI: 0.17−0.95; p = 0.03) and male gender (OR 2.52, 95%CI: 1.07−5.91; p = 0.03) were independently associated with %VO2pred. Conclusions: Men have over twice the risk of persistent limited exercise tolerance in Long-COVID than women. The decreased (A) velocity, TAPSE, GLPS, and hydration status are connected with limited exercise tolerance after COVID-19 in patients with normal LVEF.}, } @article {pmid36551891, year = {2022}, author = {Cimellaro, A and Addesi, D and Cavallo, M and Spagnolo, F and Suraci, E and Cordaro, R and Spinelli, I and Passafaro, F and Colosimo, M and Pintaudi, M and Pintaudi, C and On Behalf Of The CATAnzaro LOng Covid Cataloco Study Group, }, title = {Monoclonal Antibodies and Antivirals against SARS-CoV-2 Reduce the Risk of Long COVID: A Retrospective Propensity Score-Matched Case-Control Study.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36551891}, issn = {2227-9059}, abstract = {Long COVID is a complex condition affecting quality of life, with limited therapeutic options. We investigated the occurrence of long COVID in subjects receiving early therapy with monoclonal antibodies (mAbs) or antivirals to reduce the risk of COVID-19 progression. In this retrospective study we enrolled 737 adult patients (aged 65.16 ± 13.46; 361F), who experienced COVID-19 between January 2021 and March 2022. Antiviral or mAbs were administered to symptomatic patients who did not require oxygen therapy or hospital admission for SARS-CoV-2 infection, and who were at high risk of progression to severe disease, as identified by age > 65 years or the presence of comorbidities. Long COVID, defined as newly or persistent long-term symptoms 4 weeks after the onset of the acute illness, was reported in 204 cases (28%). Age (OR 1.03; p < 0.001), gender (OR 1.88; p < 0.001) and at least three comorbidities (OR 3.49; p = 0.049) were directly associated with long COVID; conversely, vaccination (OR 0.59; p = 0.005) and mAbs/antivirals (OR 0.44; p = 0.002) were independently associated with a reduced risk of long COVID. At a propensity-score-matched analysis, the mAbs/antivirals group had a significantly lower occurrence of long COVID in comparison with untreated controls (11% vs. 34%; p = 0.001). In conclusion, mAbs and antivirals administered against the progression of COVID-19 were associated with a reduced risk of long COVID.}, } @article {pmid36551869, year = {2022}, author = {Nunn, AVW and Guy, GW and Brysch, W and Bell, JD}, title = {Understanding Long COVID; Mitochondrial Health and Adaptation-Old Pathways, New Problems.}, journal = {Biomedicines}, volume = {10}, number = {12}, pages = {}, pmid = {36551869}, issn = {2227-9059}, abstract = {Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as "brain fog", fatigue and clotting problems. Explanations for "long COVID" include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can "tip" the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer's metabolism needs to be "tipped" back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.}, } @article {pmid36550758, year = {2022}, author = {Ufuk, F and Savaş, R}, title = {COVID-19 pneumonia: lessons learned, challenges, and preparing for the future.}, journal = {Diagnostic and interventional radiology (Ankara, Turkey)}, volume = {28}, number = {6}, pages = {576-585}, pmid = {36550758}, issn = {1305-3612}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; COVID-19 Testing ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a viral disease that causes life-threatening health problems during acute illness, causing a pandemic and millions of deaths. Although computed tomography (CT) was used as a diagnostic tool for COVID-19 in the early period of the pan demic due to the inaccessibility or long duration of the polymerase chain reaction tests, cur rent studies have revealed that CT scan should not be used to diagnose COVID-19. However, radiologic findings are vital in assessing pneumonia severity and investigating complications in patients with COVID-19. Long-term symptoms, also known as long COVID, in people recovering from COVID-19 affect patients' quality of life and cause global health problems. Herein, we aimed to summarize the lessons learned in COVID-19 pneumonia, the challenges in diagnosing the disease and complications, and the prospects for future studies.}, } @article {pmid36550205, year = {2023}, author = {Shibata, S and Kobayashi, K and Tanaka, M and Asayama, K and Yamamoto, E and Nakagami, H and Hoshide, S and Kishi, T and Matsumoto, C and Mogi, M and Morimoto, S and Yamamoto, K and Mukoyama, M and Kario, K and Node, K and Rakugi, H}, title = {COVID-19 pandemic and hypertension: an updated report from the Japanese Society of Hypertension project team on COVID-19.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {46}, number = {3}, pages = {589-600}, pmid = {36550205}, issn = {1348-4214}, mesh = {Humans ; *COVID-19/complications ; COVID-19 Vaccines ; *Hypertension/complications ; Pandemics ; Post-Acute COVID-19 Syndrome ; Renin-Angiotensin System ; SARS-CoV-2 ; }, abstract = {The number of reported cases with coronavirus disease 2019 (COVID-19) has exceeded 620 million worldwide, still having a profound impact on people's health and daily lives since its occurrence and outbreak in December 2019. From the early phase of the COVID-19 pandemic, there has been a concern that the rapid spread of this communicable disease can negatively influence non-communicable diseases. Accumulating data indicate that the restriction on the access to medical care, psychological distress, and life-style changes triggered by the pandemic have indeed affected blood pressure control in hypertensive patients. Since our previous report in 2020 that summarized the findings of the literature related to COVID-19 and hypertension, there has been a considerable progress in our understanding of the association between these two disorders; nonetheless, there are remaining challenges and emerging questions in the field. In this article, we aim to summarize the latest information on the impact of the pandemic on blood pressure control, the use of the renin-angiotensin system inhibitors in patients with COVID-19, and the blood pressure changes as one of the possible post-acute sequelae of COVID-19 (also known as long COVID). We also summarize the evidence of telemedicine and COVID-19 vaccination in hypertensive subjects, based on data available as of June 2022.}, } @article {pmid36549786, year = {2022}, author = {Palau, P and Domínguez, E and Gonzalez, C and Bondía, E and Albiach, C and Sastre, C and Martínez, ML and Núñez, J and López, L}, title = {Effect of a home-based inspiratory muscle training programme on functional capacity in postdischarged patients with long COVID: the InsCOVID trial.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {36549786}, issn = {2052-4439}, mesh = {Humans ; Female ; Adult ; Middle Aged ; Male ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; Breathing Exercises/methods ; Exercise Tolerance/physiology ; SARS-CoV-2 ; *COVID-19 ; Muscles ; }, abstract = {BACKGROUND: Fatigue and exercise intolerance are the most common symptoms in patients with long COVID.

AIMS: This study aimed to evaluate whether a home-based inspiratory muscle training (IMT) programme improves maximal functional capacity in patients' long COVID after a previous admission due to SARS-CoV-2 pneumonia.

METHODS: This study was a single-centre, blinded assessor, randomised controlled trial. Twenty-six patients with long COVID and a previous admission due to SARS-CoV-2 pneumonia were randomly assigned to receive either a 12-week IMT or usual care alone (NCT05279430). The physiotherapist and participants were not blinded. Patients allocated to the IMT arm were instructed to train at home twice daily using a threshold inspiratory muscle trainer and to maintain diaphragmatic breathing during the training session. The usual care arm received no intervention.The primary endpoint was the change in peak oxygen consumption (peakVO2). Secondary endpoints were changes in quality of life (QoL), ventilatory efficiency and chronotropic response during exercise (evaluated by chronotropic index-CIx- formula). We used linear mixed regression analysis for evaluating changes in primary and secondary endpoints.

RESULTS: The mean age of the sample and time to first visit after discharge were 50.4±12.2 years and 362±105 days, respectively. A total of 11 (42.3%) were female. At baseline, the mean of peakVO2, ventilatory efficiency and CIx were 18.9±5 mL/kg/min, 29.4±5.2 and 0.64±0.19, respectively. The IMT arm improved their peakVO2 significantly compared with usual care (+Δ 4.46 mL/kg/min, 95% CI 3.10 to 5.81; p<0.001). Similar positive findings were found when evaluating changes for CIx and some QoL dimensions. We did not find significant changes in ventilatory efficiency.

CONCLUSION: In long COVID patients with a previous admission due to SARS-CoV-2 pneumonia, IMT was associated with marked improvement in exercise capacity and QoL.

TRIAL REGISTRATION NUMBER: NCT05279430.}, } @article {pmid36549578, year = {2023}, author = {Schirinzi, T and Lattanzi, R and Maftei, D and Grillo, P and Zenuni, H and Boffa, L and Albanese, M and Simonetta, C and Bovenzi, R and Maurizi, R and Loccisano, L and Vincenzi, M and Greco, A and Di Girolamo, S and Mercuri, NB and Passali, FM and Severini, C}, title = {Substance P and Prokineticin-2 are overexpressed in olfactory neurons and play differential roles in persons with persistent post-COVID-19 olfactory dysfunction.}, journal = {Brain, behavior, and immunity}, volume = {108}, number = {}, pages = {302-308}, pmid = {36549578}, issn = {1090-2139}, mesh = {Humans ; *COVID-19 ; Neurons ; *Olfaction Disorders ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Smell ; Substance P ; }, abstract = {Persistent olfactory dysfunction (OD) is one of the most complaining and worrying complications of long COVID-19 because of the potential long-term neurological consequences. While causes of OD in the acute phases of the SARS-CoV-2 infection have been figured out, reasons for persistent OD are still unclear. Here we investigated the activity of two inflammatory pathways tightly linked with olfaction pathophysiology, namely Substance P (SP) and Prokineticin-2 (PK2), directly within the olfactory neurons (ONs) of patients to understand mechanisms of persistent post-COVID-19 OD. ONs were collected by non-invasive brushing from ten patients with persistent post-COVID-19 OD and ten healthy controls. Gene expression levels of SP, Neurokinin receptor 1, Interleukin-1β (IL-1β), PK2, PK2 receptors type 1 and 2, and Prokineticin-2-long peptide were measured in ONs by Real Time-PCR in both the groups, and correlated with residual olfaction. Immunofluorescence staining was also performed to quantify SP and PK2 proteins. OD patients, compared to controls, exhibited increased levels of both SP and PK2 in ONs, the latter proportional to residual olfaction. This work provided unprecedented, preliminary evidence that both SP and PK2 pathways may have a role in persistent post-COVID-19 OD. Namely, if the sustained activation of SP, lasting months after infection's resolution, might foster chronic inflammation and contribute to hyposmia, the PK2 expression could instead support the smell recovery.}, } @article {pmid36549172, year = {2023}, author = {He, D and Yuan, M and Dang, W and Bai, L and Yang, R and Wang, J and Ma, Y and Liu, B and Liu, S and Zhang, S and Liao, X and Zhang, W}, title = {Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge.}, journal = {Asian journal of psychiatry}, volume = {80}, number = {}, pages = {103409}, pmid = {36549172}, issn = {1876-2026}, mesh = {Humans ; *COVID-19/complications ; Patient Discharge ; Tumor Necrosis Factor-alpha ; *Cognitive Dysfunction/diagnosis ; Biomarkers ; Survivors ; }, abstract = {BACKGROUND: Emerging evidence shows that cognitive dysfunction may occur following coronavirus disease 19 (COVID-19) infection which is one of the most common symptoms reported in researches of "Long COVID". Several inflammatory markers are known to be elevated in COVID-19 survivors and the relationship between long-term inflammation changes and cognitive function remains unknown.

METHODS: We assessed cognitive function and neuropsychiatric symptoms of 66 COVID-19 survivors and 79 healthy controls (HCs) matched with sex, age, and education level using a digital, gamified cognitive function evaluation tool and questionnaires at 15 months after discharge. Venous blood samples were collected to measure cytokine levels. We performed correlation analyses and multiple linear regression analysis to identify the factors potentially related to cognitive function.

RESULTS: The COVID-19 survivors performed less well on the Trails (p = 0.047) than the HCs, but most of them did not report subjective neuropsychiatric symptoms. Intensive care unit experience (β = -2.247, p < 0.0001) and self-perceived disease severity (β = -1.522, p = 0.007) were positively correlated, whereas years of education (β = 0.098, p = 0.013) was negatively associated with the performance on the Trails. Moreover, the abnormally elevated TNF-α levels (r = -0.19, p = 0.040) were negatively correlated with performance on the Trails in COVID-19 group.

CONCLUSION: Our findings suggest that COVID-19 survivors show long-term cognitive impairment in executive function, even at 15 months after discharge. Serum TNF-α levels may be an underlying mechanism of long-term cognitive impairment in patients recovering from COVID-19.}, } @article {pmid36547424, year = {2022}, author = {Rohun, J and Dorniak, K and Faran, A and Kochańska, A and Zacharek, D and Daniłowicz-Szymanowicz, L}, title = {Long COVID-19 Myocarditis and Various Heart Failure Presentations: A Case Series.}, journal = {Journal of cardiovascular development and disease}, volume = {9}, number = {12}, pages = {}, pmid = {36547424}, issn = {2308-3425}, abstract = {(1) Background: Emerging data indicate that the ongoing COVID-19 pandemic may result in long-term cardiovascular complications, among which long COVID-19 myocarditis seems to be one of the most dangerous. Clinical presentation of cardiac inflammation ranges from almost asymptomatic to life-threatening conditions, including heart failure (HF) in different stages. (2) Methods: This is a retrospective case-series study that includes three adults with different clinical presentations of heart failure on grounds of myocarditis after initial COVID-19 infection. (3) Results: All patients had new-onset symptomatic HF of various severity: from a moderately reduced left ventricular ejection fraction in one patient to significantly reduced fractions in the remaining two. Moreover, complex ventricular arrhythmias were present in one case. All patients had confirmed past myocarditis in cardiac magnetic resonance. With optimal medical treatment, cardiac function improved, and the symptoms subsided in all cases. (4) Conclusions: In COVID-19 patients, long COVID myocarditis may be one of the severe complications of this acute disease. The heterogeneity in clinical symptoms and a paucity of specific diagnostic procedures expose the patient to the significant risk of misdiagnosing and further HF development.}, } @article {pmid36546678, year = {2024}, author = {Comber, C}, title = {Long COVID Frameworks: Examining Individual- and Population-Level Models to Assess and Improve Patient Care.}, journal = {Health promotion practice}, volume = {25}, number = {1}, pages = {22-26}, pmid = {36546678}, issn = {1552-6372}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Patient Care ; }, abstract = {Post-COVID conditions, commonly referred to as long COVID, has become of increasing interest to biomedical and public health communities. Patient advocacy is critical to not only advancing quality care outcomes for patients affected by prolonged effects of the disease, but also to contribute to our understanding of lived perspectives to ensure individual voices inform future care approaches. While there has not been a "one-size fits all" approach to standardized care, disease heterogeneity has challenged previous views that the virus is limited to single organ system infections. Stakeholders at all levels have the most impact when they collaborate and organize strategies to offer assessment and treatment in multidisciplinary settings. I propose a framework in which population- and individual-level models are integrated to enable quality outcomes while helping frontline practitioners improve their decision-making in all environments.}, } @article {pmid36543718, year = {2023}, author = {Liew, F and Talwar, S and Cross, A and Willett, BJ and Scott, S and Logan, N and Siggins, MK and Swieboda, D and Sidhu, JK and Efstathiou, C and Moore, SC and Davis, C and Mohamed, N and Nunag, J and King, C and Thompson, AAR and Rowland-Jones, SL and Docherty, AB and Chalmers, JD and Ho, LP and Horsley, A and Raman, B and Poinasamy, K and Marks, M and Kon, OM and Howard, L and Wootton, DG and Dunachie, S and Quint, JK and Evans, RA and Wain, LV and Fontanella, S and de Silva, TI and Ho, A and Harrison, E and Baillie, JK and Semple, MG and Brightling, C and Thwaites, RS and Turtle, L and Openshaw, PJM and , and , }, title = {SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.}, journal = {EBioMedicine}, volume = {87}, number = {}, pages = {104402}, pmid = {36543718}, issn = {2352-3964}, support = {MR/V028448/1/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_12014/12/MRC_/Medical Research Council/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MR/S020039/1/MRC_/Medical Research Council/United Kingdom ; COV/GLA/20/05/CSO_/Chief Scientist Office/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; G0801952/MRC_/Medical Research Council/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; G1000191/MRC_/Medical Research Council/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; G0700859/MRC_/Medical Research Council/United Kingdom ; MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MR/X009297/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; G0501425/MRC_/Medical Research Council/United Kingdom ; MC_PC_20002/MRC_/Medical Research Council/United Kingdom ; MC_UU_00036/2/MRC_/Medical Research Council/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_00008/5/MRC_/Medical Research Council/United Kingdom ; MR/S032304/1/MRC_/Medical Research Council/United Kingdom ; CH/F/21/90010/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20016/MRC_/Medical Research Council/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; *SARS-CoV-2 ; *COVID-19/prevention & control ; COVID-19 Vaccines ; Follow-Up Studies ; Vaccination ; Hospitalization ; Immunoglobulin A ; Immunoglobulin G ; Antibodies, Viral ; Antibodies, Neutralizing ; }, abstract = {BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.}, } @article {pmid36542805, year = {2023}, author = {Ora, J and Calzetta, L and Frugoni, C and Puxeddu, E and Rogliani, P}, title = {Expert guidance on the management and challenges of long-COVID syndrome: a systematic review.}, journal = {Expert opinion on pharmacotherapy}, volume = {24}, number = {3}, pages = {315-330}, doi = {10.1080/14656566.2022.2161365}, pmid = {36542805}, issn = {1744-7666}, mesh = {Humans ; *COVID-19 ; *Stress Disorders, Post-Traumatic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood.

AREAS COVERED: This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome.

EXPERT OPINION: 'Long-COVID' syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms.}, } @article {pmid36542514, year = {2023}, author = {Robertson, MM and Qasmieh, SA and Kulkarni, SG and Teasdale, CA and Jones, HE and McNairy, M and Borrell, LN and Nash, D}, title = {The Epidemiology of Long Coronavirus Disease in US Adults.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {9}, pages = {1636-1645}, doi = {10.1093/cid/ciac961}, pmid = {36542514}, issn = {1537-6591}, mesh = {Adult ; Humans ; Female ; United States/epidemiology ; Male ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Longitudinal Studies ; }, abstract = {BACKGROUND: We estimated the prevalence of long COVID and impact on daily living among a representative sample of adults in the United States.

METHODS: We conducted a population-representative survey, 30 June-2 July 2022, of a random sample of 3042 US adults aged 18 years or older and weighted to the 2020 US population. Using questions developed by the UK's Office of National Statistics, we estimated the prevalence of long COVID, by sociodemographics, adjusting for gender and age.

RESULTS: An estimated 7.3% (95% confidence interval: 6.1-8.5%) of all respondents reported long COVID, corresponding to approximately 18 828 696 adults. One-quarter (25.3% [18.2-32.4%]) of respondents with long COVID reported their day-to-day activities were impacted "a lot" and 28.9% had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection more than 12 months ago. The prevalence of long COVID was higher among respondents who were female (adjusted prevalence ratio [aPR]: 1.84 [1.40-2.42]), had comorbidities (aPR: 1.55 [1.19-2.00]), or were not (vs were) boosted (aPR: 1.67 [1.19-2.34]) or not vaccinated (vs boosted) (aPR: 1.41 [1.05-1.91]).

CONCLUSIONS: We observed a high burden of long COVID, substantial variability in prevalence of SARS-CoV-2, and risk factors unique from SARS-CoV-2 risk, suggesting areas for future research. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.}, } @article {pmid36540020, year = {2023}, author = {Maughan, ED and Thompson, ME and Walsh, CA and Issa, A and Lin, JS}, title = {Feasibility Assessment of a School Nurse-Led Approach Using Chronic Absenteeism to Establish the School-Based Active Surveillance Process.}, journal = {The Journal of school nursing : the official publication of the National Association of School Nurses}, volume = {39}, number = {2}, pages = {105-113}, doi = {10.1177/10598405221144259}, pmid = {36540020}, issn = {1546-8364}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology ; Absenteeism ; Feasibility Studies ; Nurse's Role ; Post-Acute COVID-19 Syndrome ; Watchful Waiting ; *COVID-19 ; }, abstract = {This article shares what was learned from the feasibility assessment of a nurse-led school-based active surveillance (SBAS) pilot to track chronic absenteeism using myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an exemplar. This pilot encompassed a 3-year period with training and feedback from school nurses (SNs) on data collection and ME/CFS. SNs found that the SBAS process helped them effectively identifying undiagnosed conditions. The assessment revealed the importance of focusing outreach efforts and establishing relationships with the school leadership in developing health policies and programs in the school setting. The pilot data were used to develop a manual to guide SNs for the SBAS process. This can be viewed as a model for SNs in establishing a surveillance to identify and track conditions like ME/CFS. With overlapping symptoms of Long COVID to ME/CFS, this assessment may provide insights for additional efforts to understand the impact of Long COVID on students' education.}, } @article {pmid36539931, year = {2022}, author = {Pak, VM and Lee, J}, title = {Examining the role of micronutrients on improving long COVID sleep-related symptoms.}, journal = {Journal of clinical nursing}, volume = {}, number = {}, pages = {}, pmid = {36539931}, issn = {1365-2702}, abstract = {AIMS AND OBJECTIVES: Long COVID is defined as the continuation of symptoms for four or more weeks after initial contraction of the virus. This review article examines the role of four select micronutrients (zinc, vitamins C, D and polyphenols) for their anti-inflammatory and therapeutic potential to improve sleep-related symptoms in persons with long COVID.

BACKGROUND: Evidence suggests a link between long COVID and increased inflammation. There are currently no therapeutic interventions for common sleep-related symptoms associated with long COVID. Micronutrients, due to their antioxidant and anti-inflammatory properties, may have a role in the treatment of sleep-related symptoms in the context of long COVID.

DESIGN: A narrative literature review was conducted and guided by the PRISMA checklist.

METHODS: All articles were screened from PubMed, ScienceDirect, NCBI or Google Scholar and were limited to human studies. The following keywords were used: 'COVID-19', 'sleep symptoms', 'zinc', 'vitamin C', 'vitamin D', 'polyphenols' and 'micronutrients'.

RESULTS: There are currently no studies that examine the usage of micronutrients and its impacts on long-term, sleep-related symptoms post-COVID-19 infection. We focussed our review on prior studies that examined micronutrients in the context of sleep symptoms and inflammation, while exploring the potential for micronutrients to help improve sleep-related symptoms associated with long COVID.

CONCLUSIONS: There is evidence to suggest that sleep-related symptoms associated with long COVID, such as fatigue and poor sleep quality, are associated with inflammation. Zinc, vitamins C, D and polyphenols all have the potential to improve both inflammation and sleep quality to alleviate symptoms. Future research should further examine these micronutrients in the context of long COVID to improve sleep and quality of life.

This article provides implications for clinicians to be at the forefront of research on the usage of micronutrients to improve sleep-related symptoms in persons with long COVID.}, } @article {pmid36539006, year = {2023}, author = {Harber, MP and Peterman, JE and Imboden, M and Kaminsky, L and Ashton, REM and Arena, R and Faghy, MA}, title = {Cardiorespiratory fitness as a vital sign of CVD risk in the COVID-19 era.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {44-48}, pmid = {36539006}, issn = {1873-1740}, mesh = {Humans ; *Cardiorespiratory Fitness/physiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; *Cardiovascular Diseases/diagnosis/epidemiology/prevention & control ; *COVID-19/epidemiology/complications ; Vital Signs ; Risk Factors ; Physical Fitness/physiology ; }, abstract = {The severe health consequences of the corona virus disease 2019 (COVID-19) pandemic have been exacerbated by the prevalence of cardiovascular disease (CVD) risk factors, such as physical inactivity, obesity, hypertension, and diabetes. Further, policy decisions during the pandemic augmented unhealthy lifestyle behaviors and health inequalities, likely increasing the global disease burden. Cardiorespiratory fitness (CRF) is a well-established biomarker associated with CVD risk. Emerging data demonstrate that high CRF offers some protection against severe outcomes from COVID-19 infection, highlighting the importance of CRF for population health and the potential for limiting the severity of future pandemics. CRF is best assessed by cardiopulmonary exercise testing (CPET), which will be an important tool for understanding the prolonged pathophysiology of COVID-19, the emergence of long-COVID, and the lasting effects of COVID-19 on CVD risk. Utilization of CRF and CPET within clinical settings should become commonplace because of lessons learned from the COVID-19 pandemic.}, } @article {pmid36538532, year = {2022}, author = {Arjun, MC and Singh, AK and Pal, D and Das, K and G, A and Venkateshan, M and Mishra, B and Patro, BK and Mohapatra, PR and Subba, SH}, title = {Characteristics and predictors of Long COVID among diagnosed cases of COVID-19.}, journal = {PloS one}, volume = {17}, number = {12}, pages = {e0278825}, pmid = {36538532}, issn = {1932-6203}, mesh = {Adult ; Humans ; *COVID-19/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; COVID-19 Vaccines ; Quality of Life ; }, abstract = {BACKGROUND: Long COVID or long-term symptoms after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe acute COVID-19 cases. We did this study to estimate the incidence and identify the characteristics and predictors of Long COVID among our patients.

METHODOLOGY: We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks and six months of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.

RESULTS: We have analyzed 487 and 371 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47) and 223 days (IQR:195,251), respectively. Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) and 9.4% (95% CI: 6.7%,12.9%) of participants at four weeks and six months of follow-up, respectively. Incidence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n = 72) at four weeks of follow-up. At six months, the incidence among mild/moderate (n = 319) was 7.2% (95% CI:4.6%,10.6%) as compared to 23.1% (95% CI:12.5%,36.8%) in severe/critical (n = 52). The most common Long COVID symptom was fatigue. Statistically significant predictors of Long COVID at four weeks of follow-up were-Pre-existing medical conditions (Adjusted Odds ratio (aOR) = 2.00, 95% CI: 1.16,3.44), having a higher number of symptoms during acute phase of COVID-19 disease (aOR = 11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR = 2.32, 95% CI: 1.17,4.58), the severity of illness (aOR = 5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR) = 3.89, 95% CI: 2.49,6.08).

CONCLUSION: A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.}, } @article {pmid36536440, year = {2022}, author = {Trapani, G and Verlato, G and Bertino, E and Maiocco, G and Vesentini, R and Spadavecchia, A and Dessì, A and Fanos, V}, title = {Response to commentary 'long COVID-19/post-COVID condition in children: do we all speak the same language?.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {200}, pmid = {36536440}, issn = {1824-7288}, mesh = {Humans ; Child ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Language ; Italy ; }, abstract = {Here we present the Authors' answer to the Letter written by Dr. Garazzino and Colleagues with reference to our article "Long COVID-19 in children: an Italian cohort study".}, } @article {pmid36535564, year = {2023}, author = {Zuin, M and Rigatelli, G and Battisti, V and Costola, G and Roncon, L and Bilato, C}, title = {Increased risk of acute myocardial infarction after COVID-19 recovery: A systematic review and meta-analysis.}, journal = {International journal of cardiology}, volume = {372}, number = {}, pages = {138-143}, pmid = {36535564}, issn = {1874-1754}, mesh = {Humans ; Male ; Middle Aged ; Female ; *COVID-19/complications ; SARS-CoV-2 ; *Myocardial Infarction/diagnosis/epidemiology/complications ; }, abstract = {BACKGROUND: Few studies have analyzed the incidence and the risk of acute myocardial infarction (AMI) during the post-acute phase of COVID-19 infection.

OBJECTIVE: To assess the incidence and risk of AMI in COVID-19 survivors after SARS-CoV-2 infection by a systematic review and meta-analysis of the available data.

METHODS: Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 and reporting the risk of incident AMI in patients recovered from COVID-19 infection. AMI risk was evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins and Thomson I[2] statistic.

RESULTS: Among 2765 articles obtained by our search strategy, four studies fulfilled the inclusion criteria for a total of 20,875,843 patients (mean age 56.1 years, 59.1% males). Of them, 1,244,604 had COVID-19 infection. Over a mean follow-up of 8.5 months, among COVID-19 recovered patients AMI occurred in 3.5 cases per 1.000 individuals compared to 2.02 cases per 1.000 individuals in the control cohort, defined as those who did not experience COVID-19 infection in the same period). COVID-19 patients showed an increased risk of incident AMI (HR: 1.93, 95% CI: 1.65-2.26, p < 0.0001, I[2] = 83.5%). Meta-regression analysis demonstrated that the risk of AMI was directly associated with age (p = 0.01) and male gender (p = 0.001), while an indirect relationship was observed when the length of follow-up was utilized as moderator (p < 0.001).

CONCLUSION: COVID-19 recovered patients had an increased risk of AMI.}, } @article {pmid36535372, year = {2023}, author = {Laorden, D and Domínguez-Ortega, J and Carpio, C and Barranco, P and Villamañán, E and Romero, D and Quirce, S and Álvarez-Sala, R and , }, title = {Long COVID outcomes in an asthmatic cohort and its implications for asthma control.}, journal = {Respiratory medicine}, volume = {207}, number = {}, pages = {107092}, pmid = {36535372}, issn = {1532-3064}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Asthma/complications/epidemiology/drug therapy ; *Anti-Asthmatic Agents/therapeutic use ; Administration, Inhalation ; Adrenal Cortex Hormones/therapeutic use ; }, } @article {pmid36535297, year = {2022}, author = {Vitiello, A and Ferrara, F and Zovi, A}, title = {Mechanisms and Clinical Perspectives of COVID-19-induced Cardiovascular Disease.}, journal = {Discovery medicine}, volume = {34}, number = {173}, pages = {181-187}, pmid = {36535297}, issn = {1944-7930}, mesh = {Humans ; *Cardiovascular Diseases ; *COVID-19 ; *Heart Diseases ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {COVID-19 infection can cause damage to various systems, such as cardiovascular, respiratory, and neurological, both during the course of the disease and in the period after recovery, caused by the effects of so-called "Long COVID." Cardiovascular complications caused by COVID-19 infection are not yet fully understood and characterized. Cardiovascular complications caused by COVID-19 include pericarditis, myocarditis, dysrhythmias, ischemic and non-ischemic heart disease, and thromboembolic disease. The pathophysiological and molecular mechanisms of cardiovascular damage caused by SARS-CoV-2 are still being studied. More severe COVID-19 cases with the multisystem inflammatory syndrome (MIS) have frequent involvement of cardiovascular damage. In addition, recent evidence shows that months later, individuals who have had a COVID-19 infection may be at a greater risk of suffering heart disease than individuals who have not had the infection. In this brief literature review, we summarize the current evidence in the literature on cardiovascular damage caused by COVID-19, during the period of infection and in the long COVID, and possible concomitant risk factors, which may play an important role.}, } @article {pmid36534494, year = {2022}, author = {Zięba, N and Stryjewska-Makuch, G and Goroszkiewicz, K and Zieliński, M and Dadok, A and Pietrzyk, B and Gajewska, J and Miśkiewicz-Orczyk, K and Lisowska, G}, title = {Assessment of life quality and health perception among recovered COVID-19 patients: multivariate analysis - own material and a review of previous reports on life quality assessment among convalescents.}, journal = {Medycyna pracy}, volume = {73}, number = {6}, pages = {449-456}, doi = {10.13075/mp.5893.01297}, pmid = {36534494}, issn = {2353-1339}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Quality of Life ; Pandemics ; Multivariate Analysis ; Perception ; }, abstract = {BACKGROUND: The SARS-CoV-2 virus, causing acute respiratory disease, is responsible for the COVID-19 pandemic, which began in early 2020. In addition to symptoms typical of respiratory tract infections, the virus causes a number of non-specific, often long-lasting effects that hinder the daily functioning of individuals. The aim of the study was a subjective assessment of life quality and health perception among recovered COVID-19 patients.

MATERIAL AND METHODS: The study included 337 subjects who had been infected with SARS-CoV-2 confirmed by a positive RT-PCR test. The study participants were of legal age. The convalescents completed a questionnaire that contained 26 questions about gender, height, body weight, blood type, general and specific symptoms, comorbidities, hospital stay and duration of specific symptoms, the severity of which was assessed on the Visual Analogue Scale (VAS). The subjects determined whether the COVID-19 infection influenced their health perception and life quality.

RESULTS: According to 46% of the respondents, COVID-19 had an impact on their quality of life and health. The chance for patients to notice the negative effects of COVID-19 on their current health status and life quality increased with each subsequent symptom of the disease by 49%, with each day of its occurrence by 3%, and with each VAS point of the severity of all infection symptoms by 30%.

CONCLUSIONS: The study shows that COVID-19 disease affects life quality and overall health perception after recovery. Significant impact of COVID-19 on the quality of life should be a signal to create mental support and rehabilitation programs for convalescents to minimize discomfort and shorten the duration of absenteeism from work. Med Pr. 2022;73(6):449-56.}, } @article {pmid36533738, year = {2022}, author = {Moretti, C and Collaro, C and Terzoni, C and Colucci, G and Copelli, M and Sarli, L and Artioli, G}, title = {Dealing with uncertainty. A qualitative study on the illness' experience in patients with Long-COVID in Italy.}, journal = {Acta bio-medica : Atenei Parmensis}, volume = {93}, number = {6}, pages = {e2022349}, pmid = {36533738}, issn = {2531-6745}, mesh = {Humans ; Female ; *Quality of Life ; *COVID-19 ; Uncertainty ; Post-Acute COVID-19 Syndrome ; Qualitative Research ; }, abstract = {BACKGROUND AND GOALS: An unknown proportion of people who had COVID-19 infection continue to experience symptoms such as fatigue, breathlessness, joint or muscle pain, difficulty sleeping, and brain fog. These symptoms have a significant impact on the quality of life. Long-COVID is a new multisystem disease still under investigation. This research aims to explore the illness experienced by patients suffering from Long-COVID in Italy.

RESEARCH DESIGN AND METHODS: Qualitative methodology with semi-structured interviews. Participants were recruited on the Facebook patient group between October 2021 and January 2022. Participants had been experiencing symptoms for at least three months following confirmed COVID-19 infection. Interviews were conducted by video call, recorded and transcribed with consent. The thematic analysis method has been chosen to infer data from textual material.

RESULTS: 17 interviews with women with Long-COVID have been analysed. The main themes include: a total change of life due to the symptomatology, loss of autonomy that affects social, family and professional life; social isolation, a sense of abandonment often increased by stigma, the difficulty of being believed and achieving diagnosis; difficulty in managing symptoms and accessing to care services; living with uncertainty caused by the lack of institutional, social, professional, familial and medical support.  Conclusions: Intervention programs, both institutional and social-health policies should be developed for patients with Long-COVID. The impact of symptoms could be reduced by developing standards and protocols, and by ensuring access to care and to multi-disciplinary rehabilitation. Further development of knowledge on Long-COVID is essential.}, } @article {pmid36532316, year = {2023}, author = {Fenton, C and Lee, A}, title = {Antidepressants with anti-inflammatory properties may be useful in long COVID depression.}, journal = {Drugs & therapy perspectives : for rational drug selection and use}, volume = {39}, number = {2}, pages = {65-70}, pmid = {36532316}, issn = {1172-0360}, abstract = {Long COVID, which is characterised by the presence of persistent symptoms following a COVID infection, may also cause long COVID depression (LCD). Although the risk factors for LCD are not directly characterised, prior mental health visits were associated with an increased risk for long COVID, whereas antidepressant use was not. Current evidence suggests that pro-inflammatory factors in the brain are linked to LCD, thus anti-inflammatory agents may be useful in mitigating LCD. Limited evidence suggests that selective serotonin reuptake inhibitors may also be effective in the treatment of LCD.}, } @article {pmid36531928, year = {2023}, author = {Shukla, AK and Atal, S and Banerjee, A and Jhaj, R and Balakrishnan, S and Chugh, PK and Xavier, D and Faruqui, A and Singh, A and Raveendran, R and Mathaiyan, J and Gauthaman, J and Parmar, UI and Tripathi, RK and Kamat, SK and Trivedi, N and Shah, P and Chauhan, J and Dikshit, H and Mishra, H and Kumar, R and Badyal, DK and Sharma, M and Singla, M and Medhi, B and Prakash, A and Joshi, R and Chatterjee, NS and Cherian, JJ and Kamboj, VP and Kshirsagar, N}, title = {An observational multi-centric COVID-19 sequelae study among health care workers.}, journal = {The Lancet regional health. Southeast Asia}, volume = {10}, number = {}, pages = {100129}, pmid = {36531928}, issn = {2772-3682}, abstract = {BACKGROUND: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any.

METHODS: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire.

FINDING: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19.

INTERPRETATION: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae.

FUNDING: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.}, } @article {pmid36531227, year = {2022}, author = {Cheng, ZS}, title = {Editorial: Genome-wide association studies of COVID-19 among diverse human populations.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {1088026}, pmid = {36531227}, issn = {1664-8021}, } @article {pmid36531139, year = {2022}, author = {Lokugamage, AU and Robinson, N and Pathberiya, SDC and Wong, S and Douglass, C}, title = {Respectful maternity care in the UK using a decolonial lens.}, journal = {SN social sciences}, volume = {2}, number = {12}, pages = {267}, pmid = {36531139}, issn = {2662-9283}, abstract = {Respectful maternity care (RMC) is part of a global movement addressing the previous absence of human rights in global safe maternal care guidance. RMC is grounded in kindness, compassion, dignity and respectful working conditions. The decolonisation movement in healthcare seeks to dismantle structural biases set up from a historically white, male, heteronormative Eurocentric medical system. This article applies a decolonising lens to the RMC agenda and examines barriers to its implementation in UK healthcare systems. Searches of peer-reviewed journals about decolonising maternity care in the UK revealed little. Drawing from wider information bases, we examine power imbalances constructed throughout a history of various colonial biases yet lingering in maternity care. The overarching findings of our analysis revealed 3 areas of focus: professional structures and institutional biases; power imbalances between types of staff and stakeholders of care; and person-centred care through a decolonial lens. To uproot inequity and create fairer and more respectful maternity care for women, birthing people and staff, it is vital that contemporary maternity institutions understand the decolonial perspective. This novel enquiry offers a scaffolding to undertake this process. Due to significant differences in colonial history between Western colonising powers, it is important to decolonise with respect to these different territories, histories and challenges.}, } @article {pmid36529373, year = {2023}, author = {Tene, L and Bergroth, T and Eisenberg, A and David, SSB and Chodick, G}, title = {Risk factors, health outcomes, healthcare services utilization, and direct medical costs of patients with long COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {128}, number = {}, pages = {3-10}, doi = {10.1016/j.ijid.2022.12.002}, pmid = {36529373}, issn = {1878-3511}, mesh = {Adult ; Humans ; Female ; Male ; Cohort Studies ; *COVID-19 ; Facilities and Services Utilization ; Health Care Costs ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Outcome Assessment, Health Care ; Retrospective Studies ; }, abstract = {OBJECTIVES: Data on the economic burden of long COVID are scarce. We aimed to examine the prevalence and medical costs of treating long COVID.

METHODS: We conducted this historical cohort study using data from patients with COVID-19 among members of a large health provider in Israel. Cases were defined according to physician diagnosis (definite long COVID) or suggestive symptoms given ≥ 4 weeks from infection (probable cases). Healthcare resource utilization and direct healthcare costs (HCCs) in the period before infection and afterward were compared across study groups.

RESULTS: Between March 2020, and March 2021, a total of 180,759 COVID-19 patients (mean [SD] age = 32.9 years [19.0 years]; 89,665 [49.6%] females) were identified. Overall, 14,088 (7.8%) individuals developed long COVID (mean [SD] age = 40.0 years [19.0 years]; 52.4% females). Among them, 1477(10.5%) were definite long COVID and 12,611(89.5%) were defined as probable long COVID. Long COVID was associated with age (adjusted odds ratio [AOR] = 1.058 per year, 95% CI: 1.053-1.063), female sex (AOR = 1.138; 95% CI: 1.098-1.180), smoking (AOR = 1.532; 95% CI: 1.358-1.727), and symptomatic acute phase (AOR = 1.178; 95% CI: 1.133-1.224), primarily muscle pain and cough. Hypertension was an important risk factor for long COVID among younger adults. Compared with patients with non-long COVID, definite and probable cases were associated with AORs of 2.47 (2.22-2.75) and 1.76 (1.68-1.84) for post-COVID hospitalization, respectively. Although among patients with non-long COVID HCCs decreased from $1400 during 4 months before the infection to $1021 and among patients with long COVID, HCCs increased from $2435 to $2810.

CONCLUSION: Long COVID is associated with a substantial increase in the utilization of healthcare services and direct medical costs. Our findings underline the need for timely planning and allocating resources for patient-centered care for patients with long COVID as well as for its secondary prevention in high-risk patients.}, } @article {pmid36528708, year = {2023}, author = {Milojkovic, D and Reynolds, CJ and Sandoval, DM and Pieper, FP and Liu, S and Pade, C and Gibbons, JM and McKnight, Á and Loaiza, S and Palanicawander, R and Innes, AJ and Claudiani, S and Apperley, JF and Altmann, DM and Boyton, RJ}, title = {COVID-19 vaccine boosted immunity against Omicron in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.}, journal = {Leukemia}, volume = {37}, number = {1}, pages = {244-247}, pmid = {36528708}, issn = {1476-5551}, support = {21011/LLR_/Blood Cancer UK/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; COVID-19 Vaccines ; Tyrosine Kinase Inhibitors ; *COVID-19 ; Imatinib Mesylate ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; }, } @article {pmid36528073, year = {2023}, author = {Holland, C and Hammond, C and Richmond, MM}, title = {COVID-19 and Pregnancy: Risks and Outcomes.}, journal = {Nursing for women's health}, volume = {27}, number = {1}, pages = {31-41}, pmid = {36528073}, issn = {1751-486X}, mesh = {Pregnancy ; Infant ; Infant, Newborn ; Female ; Humans ; *COVID-19 ; SARS-CoV-2 ; *Pregnancy Complications, Infectious/prevention & control ; Parturition ; Delivery, Obstetric ; Pregnancy Outcome/epidemiology ; }, abstract = {The normal physiologic changes of pregnancy are known to increase susceptibility to respiratory illness. Individuals who are pregnant are more likely to acquire a SARS-CoV-2 infection and develop COVID-19 than the general population; they are at increased risk for hospitalization; ventilator-assisted breathing; and other subsequent maternal, fetal, and neonatal health issues. Although the incidence of infection and subsequent morbidity is increased in pregnancy, mortality does not seem to be increased. Individuals who are vaccinated against COVID-19 before childbirth can pass antibodies to their fetuses via the placenta during pregnancy and to their infants during breastfeeding. It is important for health care providers to be cognizant of the potential impacts of COVID-19 on pregnant individuals and their offspring.}, } @article {pmid36526981, year = {2022}, author = {Gindlhuber, J and Tomin, T and Wiesenhofer, F and Zacharias, M and Liesinger, L and Demichev, V and Kratochwill, K and Gorkiewicz, G and Schittmayer, M and Birner-Gruenberger, R}, title = {Proteomic profiling of end-stage COVID-19 lung biopsies.}, journal = {Clinical proteomics}, volume = {19}, number = {1}, pages = {46}, pmid = {36526981}, issn = {1542-6416}, support = {W 1226/FWF_/Austrian Science Fund FWF/Austria ; 161L0221//German Ministry of Education and Research (BMBF)/ ; F73//Austrian Science Fund/ ; W1226//Austrian Science Fund/ ; }, abstract = {The outbreak of a novel coronavirus (SARS-CoV-2) in 2019 led to a worldwide pandemic, which remains an integral part of our lives to this day. Coronavirus disease (COVID-19) is a flu like condition, often accompanied by high fever and respiratory distress. In some cases, conjointly with other co-morbidities, COVID-19 can become severe, leading to lung arrest and even death. Although well-known from a clinical standpoint, the mechanistic understanding of lethal COVID-19 is still rudimentary. Studying the pathology and changes on a molecular level associated with the resulting COVID-19 disease is impeded by the highly infectious nature of the virus and the concomitant sampling challenges. We were able to procure COVID-19 post-mortem lung tissue specimens by our collaboration with the BSL-3 laboratory of the Biobanking and BioMolecular resources Research Infrastructure Austria which we subjected to state-of-the-art quantitative proteomic analysis to better understand the pulmonary manifestations of lethal COVID-19. Lung tissue samples from age-matched non-COVID-19 patients who died within the same period were used as controls. Samples were subjected to parallel accumulation-serial fragmentation combined with data-independent acquisition (diaPASEF) on a timsTOF Pro and obtained raw data was processed using DIA-NN software. Here we report that terminal COVID-19 patients display an increase in inflammation, acute immune response and blood clot formation (with concomitant triggering of fibrinolysis). Furthermore, we describe that COVID-19 diseased lungs undergo severe extracellular matrix restructuring, which was corroborated on the histopathological level. However, although undergoing an injury, diseased lungs seem to have impaired proliferative and tissue repair signalling, with several key kinase-mediated signalling pathways being less active. This might provide a mechanistic link to post-acute sequelae of COVID-19 (PASC; "Long COVID"). Overall, we emphasize the importance of histopathological patient stratification when interpreting molecular COVID-19 data.}, } @article {pmid36526333, year = {2023}, author = {Tuffnell, R and Sayers, P and Davis, E and Chan, E and Burkin, J and Moffat, C and Traub, C and Sheldon, M and Booth, S and Spathis, A}, title = {Palliative care symptom management expertise for long-COVID.}, journal = {BMJ supportive & palliative care}, volume = {13}, number = {1}, pages = {61-62}, doi = {10.1136/spcare-2022-004032}, pmid = {36526333}, issn = {2045-4368}, mesh = {Humans ; *Palliative Care ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36525872, year = {2023}, author = {Capela Santos, D and Jaconiano, S and Macedo, S and Ribeiro, F and Ponte, S and Soares, P and Boaventura, P}, title = {Yoga for COVID-19: An ancient practice for a new condition - A literature review.}, journal = {Complementary therapies in clinical practice}, volume = {50}, number = {}, pages = {101717}, pmid = {36525872}, issn = {1873-6947}, mesh = {Humans ; *Yoga/psychology ; *Meditation ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; *COVID-19/therapy ; }, abstract = {A substantial proportion of people with acute COVID-19 develop post-COVID-19 condition (previously known as long-COVID) characterized by symptoms that persist for months after the initial infection, including neuropsychological sequelae. Post-COVID-19 condition frequency varies greatly according to different studies, with values ranging from 4 to 80% of the COVID-19 patients. Yoga is a psycho-somatic approach that increases physical, mental, emotional and spiritual strength, and connection. Yoga practice enhances innate immunity and mental health, so it can be used as complementary therapy in the COVID-19 treatment, namely the post-COVID-19 condition. In this article, we conducted a literature review on yoga and COVID-19, finding that an intervention comprising asana, pranayama, and meditation may be a strategy of choice for these patients' recovery. However, further studies are needed to show its effectiveness in this, still unknown, context.}, } @article {pmid36523412, year = {2022}, author = {Durstenfeld, MS and Peluso, MJ and Peyser, ND and Lin, F and Knight, SJ and Djibo, A and Khatib, R and Kitzman, H and O'Brien, E and Williams, N and Isasi, C and Kornak, J and Carton, TW and Olgin, JE and Pletcher, MJ and Marcus, GM and Beatty, AL}, title = {Factors Associated with Long Covid Symptoms in an Online Cohort Study.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36523412}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; }, abstract = {IMPORTANCE: Prolonged symptoms following SARS-CoV-2 infection, or Long COVID, is common, but few prospective studies of Long COVID risk factors have been conducted.

OBJECTIVE: To determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID.

DESIGN: Cohort study with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection, and cross-sectional assessment of Long COVID symptoms using data from the COVID-19 Citizen Science (CCS) study.

SETTING: CCS is an online cohort study that began enrolling March 26, 2020. We included data collected between March 26, 2020, and May 18, 2022.

PARTICIPANTS: Adult CCS participants who reported a positive SARS-CoV-2 test result (PCR, Antigen, or Antibody) more than 30 days prior to May 4, 2022, were surveyed.

EXPOSURES: Age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, time of infection (variant wave), number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, exercise.

MAIN OUTCOME: Presence of at least 1 Long COVID symptom greater than 1 month after acute infection. Sensitivity analyses were performed considering only symptoms beyond 3 months and only severe symptoms.

RESULTS: 13,305 participants reported a SARS-CoV-2 positive test more than 30 days prior, 1480 (11.1% of eligible) responded to a survey about Long COVID symptoms, and 476 (32.2% of respondents) reported Long COVID symptoms (median 360 days after infection).Respondents' mean age was 53 and 1017 (69%) were female. Common Long COVID symptoms included fatigue, reported by 230/476 (48.3%), shortness of breath (109, 22.9%), confusion/brain fog (108, 22.7%), headache (103, 21.6%), and altered taste or smell (98, 20.6%). In multivariable models, number of acute COVID-19 symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms.

CONCLUSIONS AND RELEVANCE: Variant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.

KEY POINTS: Question: What are the patterns of symptoms and risk factors for Long COVID among SARS-CoV-2 infected individuals?Findings: Persistent symptoms were highly prevalent, especially fatigue, shortness of breath, headache, brain fog/confusion, and altered taste/smell, which persisted beyond 1 year among 56% of participants with symptoms; a minority of participants reported severe Long COVID symptoms. Number of acute symptoms during acute SARS-CoV-2 infection, financial insecurity, pre-existing depression, and infection with earlier variants are associated with prevalent Long COVID symptoms independent of vaccination, medical history, and other factors.Meaning: Severity of acute infection, SARS-CoV-2 variant, and financial insecurity and depression are associated with Long COVID symptoms.}, } @article {pmid36523407, year = {2022}, author = {Ghosh, P and Niesen, MJM and Pawlowski, C and Bandi, H and Yoo, U and Lenehan, PJ and M, PK and Nadig, M and Ross, J and Ardhanari, S and O'Horo, JC and Venkatakrishnan, AJ and Rosen, CJ and Telenti, A and Hurt, RT and Soundararajan, V}, title = {Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36523407}, abstract = {Post-COVID-19 conditions, also known as "long COVID", has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.}, } @article {pmid36523402, year = {2022}, author = {Lau, B and Wentz, E and Ni, Z and Yenokyan, K and Coggiano, C and Mehta, SH and Duggal, P}, title = {Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36523402}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, abstract = {IMPORTANCE: Persistent symptoms after SARS-COV-2 infection, or long-COVID, may occur in anywhere from 10-55% of those who have had COVID-19, but the extent of impact on daily functioning and disability remains unquantified.

OBJECTIVE: To characterize physical and mental disability associated with long-COVID.

DESIGN: Cross-sectional analysis of baseline data from a cohort study.

SETTING: Online US nationwide survey.

PARTICIPANTS: Adults 18 years of age and older who live in the US who either report a history of COVID-19 illness (n=8,874) or report never having had COVID-19 (n=633).

MAIN OUTCOME AND MEASURES: Self-reported mobility disability (difficulty walking a quarter of a mile and/or up 10 stairs, instrumental activities of daily living [IADL] disability (difficulty doing light or heavy housework), and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI).

RESULTS: Of 7,926 participants with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity. Sixty-five percent of long-COVID participants were classified as having at least one disability, compared to 6% of those with resolved-COVID (n=948) and 14% of those with no-COVID (n=633). Of long-COVID participants, about 1% and 5% were classified as critically physically disabled or mentally fatigued, respectively. Age, prior comorbidity, increased BMI, female gender, hospitalization for COVID-19, non-white race, and multi-race were all associated with significantly higher disability burden. Dizziness at the time of infection (33% non-hospitalized, 39% hospitalized) was associated with all five disability components in both hospitalized and non-hospitalized groups. Heavy limbs, dyspnea, and tremors were associated with four of the five components of disability in the non-hospitalized group, and heavy limbs was associated with four of the five components in the hospitalized group. Vaccination was protective against development of disability.

CONCLUSION AND RELEVANCE: We observed a high burden of physical and mental disability associated with long-COVID which has serious implications for individual and societal health that may be partially mitigated by vaccination. Longitudinal characterization and evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.}, } @article {pmid36520039, year = {2022}, author = {Guziejko, K and Tałałaj, J and Czupryna, P and Moniuszko-Malinowska, A}, title = {Long COVID.}, journal = {Przeglad epidemiologiczny}, volume = {76}, number = {3}, pages = {287-295}, doi = {10.32394/pe.76.27}, pmid = {36520039}, issn = {0033-2100}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Poland/epidemiology ; Pandemics ; }, abstract = {The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was primarily focused on the involvement of the respiratory system, as the most common clinical manifestation of the disease. Currently, also long COVID poses a significant problem for medicine and public health worldwide. It is characterized by persistent symptoms from various organs or systems, often present for several weeks and months after acute phase of SARS-CoV-2 infection. Currently, the most frequently used description for long COVID referred to symptoms that last more than three months after the onset. Numerous data confirm long-term effects of COVID-19, including pulmonary, cardiovascular, neurological, renal, hematologic, gastrointestinal, endocrine and psychosocial manifestations. It is necessary to monitor patients after acute phase of COVID-19 to detect and treat possible multi-organ long-term consequences of SARS-CoV-2 infection.}, } @article {pmid36518871, year = {2022}, author = {Heller, O and Chun, Y and Shapira, S and Troen, A and Shlomo, Y and Acri, M and Marotta, P and Kulkarni, S and Kinnison, B and Grinstein-Weiss, M}, title = {Prevalence of Long-COVID Among Low-Income and Marginalized Groups: Evidence From Israel.}, journal = {International journal of public health}, volume = {67}, number = {}, pages = {1605086}, pmid = {36518871}, issn = {1661-8564}, mesh = {Humans ; *SARS-CoV-2 ; Israel/epidemiology ; *COVID-19/epidemiology ; Prevalence ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; }, abstract = {Objective: To identify the socioeconomic and demographic factors associated with the prevalence of self-reported long-COVID symptoms. Method: We examined the association between acute-COVID (SARS-CoV-2) and long-COVID symptoms, by a cross-sectional analysis of data obtained on a prospective online-survey, conducted from November to December 2021 on a nationally-representative sample of the Israeli population (N = 2,246). Results: Findings suggest that there is a greater likelihood of experiencing long-COVID symptoms among low-income and among marginalized groups. After controlling for demographic and socioeconomic attributes, those who had moderate/severe acute-COVID were 1.3 (p < 0.05) times more likely to experience a long-term symptom and also reported more long-term symptoms (2.2 symptoms) than those who have not been infected (1.4 symptoms; p < 0.01). Among the low-income group, a larger gap in symptom count was found between those who had moderate/severe acute-COVID (3.3 symptoms) and those who had not been infected (1.8 symptoms, p < 0.05). Conclusion: Our findings highlight the importance of raising awareness of long-COVID among marginalized population groups, and to the therapeutic options available. Such efforts should be tailored and should consider the unique socioeconomic and cultural characteristics, as well as the preexisting low access to healthcare services among these groups.}, } @article {pmid36518782, year = {2022}, author = {Brasseler, M and Schönecker, A and Steindor, M and Della Marina, A and Bruns, N and Dogan, B and Felderhoff-Müser, U and Hebebrand, J and Dohna-Schwake, C and Goretzki, SC}, title = {Development of restrictive eating disorders in children and adolescents with long-COVID-associated smell and taste dysfunction.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {1022669}, pmid = {36518782}, issn = {2296-2360}, abstract = {BACKGROUND: Absent or abnormal senses of smell and taste have been frequently reported during both acute and long COVID in adult patients. In contrast, pediatric patients who test positive for SARS-CoV-2 are often asymptomatic and the loss of smell and/or taste has been infrequently reported. After observing several young patients with COVID-associated anosmia and ageusia at our clinic, we decided to investigate the incidence of subsequent eating disorders in these patients and in SARS-CoV-2 positive patients who did not experience anosmia and ageusia during the same period.

MATERIAL AND METHODS: A single-site retrospective cohort study of 84 pediatric patients with suspected long COVID who were treated in the Pediatric Infectious Diseases Outpatient Clinic at the University Hospital Essen were evaluated for persistent symptoms of COVID-19. Smell and taste dysfunction as well as eating behaviors were among the signs and symptoms analyzed in this study.

RESULTS: 24 out of 84 children and adolescents described smell and taste dysfunction after confirmed or suspected SARS-CoV-2 infections. A large number of these patients (6 out of 24) demonstrated increased fixation on their eating behavior post-COVID and over time these patients developed anorexia nervosa.

DISCUSSION/CONCLUSION: In this study we saw a possible association of long-lasting post-COVID smell and taste dysfunction with subsequent development of eating disorders. This observation is worrisome and merits further investigation by healthcare providers at multiple clinical sites.}, } @article {pmid36517845, year = {2022}, author = {Das, S and Taylor, K and Kozubek, J and Sardell, J and Gardner, S}, title = {Genetic risk factors for ME/CFS identified using combinatorial analysis.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {598}, pmid = {36517845}, issn = {1479-5876}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; COVID-19/complications ; *Fatigue Syndrome, Chronic/genetics ; *Fibromyalgia/genetics ; Post-Acute COVID-19 Syndrome/genetics ; Reproducibility of Results ; Risk Factors ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.

METHODS: We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and compared results for overlap and reproducibility.

RESULTS: Combinatorial analysis revealed 199 SNPs mapping to 14 genes that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3 and 5 SNPs. p-values for these communities range from 2.3 × 10[-10] to 1.6 × 10[-72]. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS.

CONCLUSIONS: This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.}, } @article {pmid36515147, year = {2023}, author = {Luvizutto, GJ and Bazan, R}, title = {Electrophysiological and neuroimaging tools to evaluate neurological symptoms, manifestations, and complications in patients with long COVID-19.}, journal = {Neurologia i neurochirurgia polska}, volume = {57}, number = {1}, pages = {8-10}, doi = {10.5603/PJNNS.a2022.0077}, pmid = {36515147}, issn = {0028-3843}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Nervous System Diseases/diagnostic imaging/etiology ; SARS-CoV-2 ; Neuroimaging ; }, } @article {pmid36514781, year = {2022}, author = {He, ST and Wu, K and Cheng, Z and He, M and Hu, R and Fan, N and Shen, L and Li, Q and Fan, H and Tong, Y}, title = {Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions.}, journal = {MedComm}, volume = {3}, number = {4}, pages = {e196}, pmid = {36514781}, issn = {2688-2663}, abstract = {COVID-19 caused by SARS-CoV-2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS-CoV-2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID. We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs. Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID-19.}, } @article {pmid36513284, year = {2023}, author = {Dini, FL and Baldini, U and Bytyçi, I and Pugliese, NR and Bajraktari, G and Henein, MY}, title = {Acute pericarditis as a major clinical manifestation of long COVID-19 syndrome.}, journal = {International journal of cardiology}, volume = {374}, number = {}, pages = {129-134}, pmid = {36513284}, issn = {1874-1754}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/complications/diagnosis ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; *Pericarditis/diagnosis/epidemiology ; Pericardium ; }, abstract = {BACKGROUND: The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis.

METHODS: We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines.

RESULTS: Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512).

CONCLUSION: Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.}, } @article {pmid36513053, year = {2022}, author = {Kim, SG and Kwon, HC and Kang, TK and Kwak, MY and Lee, S and Lee, K and Ko, K}, title = {COVID-19 Sequelae and Their Implications on Social Services.}, journal = {Journal of Korean medical science}, volume = {37}, number = {48}, pages = {e342}, pmid = {36513053}, issn = {1598-6357}, mesh = {Male ; Humans ; Female ; Middle Aged ; Quality of Life ; *Frailty ; Aftercare ; Prospective Studies ; *COVID-19/epidemiology ; Patient Discharge ; Social Work ; Disease Progression ; Taste Disorders ; Fatigue/epidemiology/etiology ; }, abstract = {BACKGROUND: The impact of persistent coronavirus disease 2019 (COVID-19) symptoms on quality of life remains unclear. This study aimed to describe such persistent symptoms and their relationships with quality of life, including clinical frailty and subjective health status.

METHODS: A prospective longitudinal 3-month follow-up survey monitored symptoms, health quality, support needs, frailty, and employment.

RESULTS: A total of 82 patients with a mean age of 52 years (ranging from 23-84 years) were enrolled, including 48 (58.6%) men, and 34 (41.5%) women. The fully active status decreased from 87.8% before admission to 78.1% post discharge. Two patients (2.4%) were ambulatory and capable of all self-care but unable to carry out any work-related activities 12 weeks after discharge. Clinical frailty scale (CFS) levels 1, 2, 3 and 4 changed drastically between admission and 12 weeks later after discharge. Just after admission, the median EuroQol visual analogue scales (EQ-VAS) was 82.23 (± 14.38), and it decreased to 78.10 (± 16.02) 12 weeks after discharge; 62 (75.6%) of patients reported at least one symptom 12 weeks after discharge. The most frequent symptom was fatigue followed by smell disorder, anxiety, sleep disorder, headache, depressive mood, dyspnea, and taste disorder. CFS was definitively associated with fatigue. Decreased EQ-VAS was associated with fatigue and palpitation, cough, taste disorder, and chest pain. EQ-VAS was worse in women (28%) than in men. Compared with regular outpatient clinic visits before admission, 21 patients (25.6%) reported increased outpatient clinic visits, one (1.4%) reported readmission, and one (1.4%) reported emergency room visits. Six of the 54 (77.1%) patients who were employed before admission lost their jobs. And most vulnerable type was self-employed, because three self-employed job workers were not working at 12 weeks after discharge.

CONCLUSION: COVID-19 sequelae should not be underestimated. We find a decrease in health quality and increase in psychological problems in discharged COVID-19 patients, and some patients experience unemployment. The number of patients suffering from COVID-19 sequelae would not be negligible considering there are more than one million COVID-19 infection cases in Korea. Hence, the government should start a systematic monitoring system for discharged patients and prepare timely medical and social interventions accordingly.}, } @article {pmid36512382, year = {2023}, author = {Baz, SA and Fang, C and Carpentieri, JD and Sheard, L}, title = {'I don't know what to do or where to go'. Experiences of accessing healthcare support from the perspectives of people living with Long Covid and healthcare professionals: A qualitative study in Bradford, UK.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {26}, number = {1}, pages = {542-554}, pmid = {36512382}, issn = {1369-7625}, support = {MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; COV-LT-0009/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Ethnicity ; Minority Groups ; *COVID-19/epidemiology ; Health Services Accessibility ; Qualitative Research ; United Kingdom ; *General Practitioners ; }, abstract = {BACKGROUND: In October 2022, it was estimated 2.3 million people in the United Kingdom have self-reported Long Covid (LC). Many people have reported not receiving adequate healthcare support. There is a lack of research which provides an in-depth exploration of the barriers faced by people with LC in accessing healthcare support. It is important to understand these barriers to provide better support, care and advice for those experiencing LC.

OBJECTIVE: To understand the barriers faced in accessing primary, secondary and specialist healthcare support for people with LC.

DESIGN AND PARTICIPATION: 40 interviews were conducted with people living with LC in Bradford alongside 12 interviews with healthcare professionals (HCPs) providing LC support in Bradford healthcare settings. Interviews were analysed using reflexive thematic analysis.

RESULTS: People living with LC had a large degree of difficulty in accessing healthcare services for LC support. We categorized the healthcare access experiences of participants into five main types: (1) being unable to access primary care, (2) accessing primary care but receiving (perceived) inadequate support, (3) extreme persistence, (4) alternatives to mainstream health care and (5) positive experiences. There was a severe lack of access to specialist LC services. Ethnic minority participants faced a further barrier of mistrust and fear of services deterring them from accessing support. HCPs discussed systemic barriers to delivering services. Experiences were embedded in macrostructural issues further exacerbated by the pandemic.

CONCLUSION: To better support people with LC, the barriers faced in accessing healthcare support must be addressed. Of significance, improvements to general practitioner access are required; especially as GPs are the first line of support for people living with LC.

A patient and public involvement group is engaged at regular intervals in the project.}, } @article {pmid36510683, year = {2023}, author = {Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Ruiz-Galiana, J and Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Bouza, E}, title = {Insights for COVID-19 in 2023.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {36}, number = {2}, pages = {114-124}, pmid = {36510683}, issn = {1988-9518}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; SARS-CoV-2 ; }, abstract = {Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.}, } @article {pmid36509479, year = {2022}, author = {Trochet, C}, title = {[Caregivers are also concerned by the Covid long].}, journal = {Revue de l'infirmiere}, volume = {71}, number = {284}, pages = {35-36}, doi = {10.1016/j.revinf.2022.10.010}, pmid = {36509479}, issn = {1293-8505}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Caregivers ; Pandemics ; Health Personnel ; }, abstract = {In the front line, from the beginning of the pandemic, to take care of patients hospitalized for severe forms of Covid-19, health professionals have not failed, despite the precautions taken, to contract the virus and develop the disease, sometimes with severe forms. Two hospital caregivers testify about their respective experiences and the repercussions on their daily life due to a long Covid.}, } @article {pmid36509476, year = {2022}, author = {Maoz, Z and Rich, S and Sudres, JL and Bouchard, JP}, title = {[Psychological support for long Covid patients during a rehabilitation stay].}, journal = {Revue de l'infirmiere}, volume = {71}, number = {284}, pages = {26-28}, doi = {10.1016/j.revinf.2022.10.007}, pmid = {36509476}, issn = {1293-8505}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Patients ; }, abstract = {Covid long affects each patient differently. This disorder can occur in people with both severe and mild forms of the disease. It is often a series of symptoms that disrupt different areas of life in a very variable way. These symptoms can change rapidly. Moreover, several symptoms are associated and fluctuate (between aggravation and recovery) during very variable periods, which leads to a mosaic diagnosis and engages the need for multidisciplinary management.}, } @article {pmid36509473, year = {2022}, author = {Barizien, N}, title = {[Recommendations for the management of long Covid].}, journal = {Revue de l'infirmiere}, volume = {71}, number = {284}, pages = {18-20}, doi = {10.1016/j.revinf.2022.10.004}, pmid = {36509473}, issn = {1293-8505}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {As we enter the eighth wave of pandemic Covid-19 infection, the disabling persistence of certain symptoms after this viral infection, often trivial with the latest variants, is still a concern. The most effective treatment of these prolonged symptoms after Covid remains a rapid diagnosis, even if it is primarily of elimination, followed by comprehensive, multidisciplinary, specialized management and early but individualized self-help exercises.}, } @article {pmid36509472, year = {2022}, author = {Warnet, S}, title = {[Post-Covid Affection, an adapted management is necessary].}, journal = {Revue de l'infirmiere}, volume = {71}, number = {284}, pages = {16-17}, doi = {10.1016/j.revinf.2022.10.003}, pmid = {36509472}, issn = {1293-8505}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Critical Pathways ; Health Personnel ; Post-Acute COVID-19 Syndrome ; }, abstract = {Covid-19 is a polymorphic disease, characterized in some patients by persistent symptoms several weeks or even months after the initial manifestations of SARS-CoV-2 infection. This is referred to as "long Covid" or post-Covid-19 disease. The polysymptomatic and fluctuating nature of these clinical manifestations generates questions and concerns for patients. To meet their care needs, the regional health agencies have worked with local health care providers to develop appropriate care pathways.}, } @article {pmid36509178, year = {2023}, author = {Hira, R and Baker, JR and Siddiqui, T and Ranada, SI and Soroush, A and Karalasingham, K and Ahmad, H and Mavai, V and Ayala Valani, LM and Ambreen, S and Bourne, KM and Lloyd, MG and Morillo, CA and Sheldon, RS and Raj, SR and , }, title = {Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19.}, journal = {The Canadian journal of cardiology}, volume = {39}, number = {6}, pages = {767-775}, pmid = {36509178}, issn = {1916-7075}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *COVID-19/complications/epidemiology ; Hemodynamics ; *Cardiovascular System ; *Hypotension, Orthostatic/diagnosis/epidemiology/etiology ; Autonomic Nervous System ; Disease Progression ; }, abstract = {BACKGROUND: Many COVID-19 patients are left with symptoms several months after resolution of the acute illness; this syndrome is known as post-acute sequalae of COVID-19 (PASC). We aimed to determine the prevalence of objective hemodynamic cardiovascular autonomic abnormalities (CAA), explore sex differences, and assess the prevalence of CAA among hospitalized vs nonhospitalized patients with PASC.

METHODS: Patients with PASC (n = 70; female [F] = 56; 42 years of age; 95% confidence interval [CI], 40-48) completed standard autonomic tests, including an active stand test 399 days (338, 455) after their COVID-19 infection. Clinical autonomic abnormalities were evaluated.

RESULTS: Most patients with PASC met the criteria for at least 1 CAA (51; 73%; F = 43). The postural orthostatic tachycardia syndrome hemodynamic (POTSHR) criterion of a heart rate increase of > 30 beats per minute within 5 to 10 minutes of standing was seen in 21 patients (30%; F = 20; P = 0.037 [by sex]). The initial orthostatic hypotension hemodynamic (IOH40) criterion of a transient systolic blood pressure change of > 40 mm Hg in the first 15 seconds of standing was seen in 43 (61%) patients and equally among female and male patients (63% vs 57%; P = 0.7). Only 9 (13%) patients were hospitalized; hospitalized vs nonhospitalized patients had similar frequencies of abnormalities (67% vs 74%; P = 0.7).

CONCLUSIONS: Patients with PASC have evidence of CAA, most commonly IOH40, which will be missed unless an active stand test is used. Female patients have increased frequency of POTSHR, but IOH40 is equally prevalent between sexes. Finally, even nonhospitalized "mild" infections can result in long-term CAAs.}, } @article {pmid36508159, year = {2023}, author = {Vink, M and Grande, T and Kohl, M}, title = {Letter to the Editor Regarding Fleischer et al. Neurological Study Does Not Provide Any Evidence that Long COVID is Psychosomatic.}, journal = {Neurology and therapy}, volume = {12}, number = {1}, pages = {329-332}, pmid = {36508159}, issn = {2193-8253}, } @article {pmid36508158, year = {2023}, author = {Stettner, M and Fleischer, M and Skoda, EM and Teufel, M and Kleinschnitz, C}, title = {Response Letter to Vink et al. 'Neurological Study Does Not Provide Any Evidence that Long COVID is Psychosomatic'.}, journal = {Neurology and therapy}, volume = {12}, number = {1}, pages = {333-336}, pmid = {36508158}, issn = {2193-8253}, } @article {pmid36507615, year = {2023}, author = {Yan, CH and Jang, SS and Lin, HC and Ma, Y and Khanwalkar, AR and Thai, A and Patel, ZM}, title = {Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial.}, journal = {International forum of allergy & rhinology}, volume = {13}, number = {6}, pages = {989-997}, pmid = {36507615}, issn = {2042-6984}, support = {K08 DC019956/DC/NIDCD NIH HHS/United States ; K08DC019956/DC/NIDCD NIH HHS/United States ; }, mesh = {Humans ; Anosmia/therapy ; *Olfaction Disorders/therapy ; *COVID-19/therapy ; Smell/physiology ; *Platelet-Rich Plasma ; }, abstract = {INTRODUCTION: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss.

METHODS: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale.

RESULTS: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported.

CONCLUSION: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.}, } @article {pmid36507225, year = {2023}, author = {Kovarik, JJ and Bileck, A and Hagn, G and Meier-Menches, SM and Frey, T and Kaempf, A and Hollenstein, M and Shoumariyeh, T and Skos, L and Reiter, B and Gerner, MC and Spannbauer, A and Hasimbegovic, E and Schmidl, D and Garhöfer, G and Gyöngyösi, M and Schmetterer, KG and Gerner, C}, title = {A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105717}, pmid = {36507225}, issn = {2589-0042}, abstract = {To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnitines. A model considering alternatively polarized macrophages as a major contributor to these molecular alterations is presented.}, } @article {pmid36507117, year = {2023}, author = {Maclean, A and Hunt, K and Brown, A and Evered, JA and Dowrick, A and Fokkens, A and Grob, R and Law, S and Locock, L and Marcinow, M and Smith, L and Urbanowicz, A and Verheij, N and Wild, C}, title = {Negotiation of collective and individual candidacy for long Covid healthcare in the early phases of the Covid-19 pandemic: Validated, diverted and rejected candidacy.}, journal = {SSM. Qualitative research in health}, volume = {3}, number = {}, pages = {100207}, pmid = {36507117}, issn = {2667-3215}, support = {COV/LTE/20/04/CSO_/Chief Scientist Office/United Kingdom ; UL1 TR002373/TR/NCATS NIH HHS/United States ; }, abstract = {This analysis of people's accounts of establishing their need and experiences of healthcare for long Covid (LC) symptoms draws on interview data from five countries (UK, US, Netherlands, Canada, Australia) during the first ∼18 months of the Covid-19 pandemic when LC was an emerging, sometimes contested, condition with scant scientific or lay knowledge to guide patients and professionals in their sense-making of often bewildering constellations of symptoms. We extend the construct of candidacy to explore positive and (more often) negative experiences that patients reported in their quest to understand their symptoms and seek appropriate care. Candidacy usually considers how individuals negotiate healthcare access. We argue a crucial step preceding individual claims to candidacy is recognition of their condition through generation of collective candidacy. "Vanguard patients" collectively identified, named and fought for recognition of long Covid in the context of limited scientific knowledge and no established treatment pathways. This process was technologically accelerated via social media use. Patients commonly experienced "rejected" candidacy (feeling disbelieved, discounted/uncounted and abandoned, and that their suffering was invisible to the medical gaze and society). Patients who felt their candidacy was "validated" had more positive experiences; they appreciated being believed and recognition of their changed lives/bodies and uncertain futures. More positive healthcare encounters were described as a process of "co-experting" through which patient and healthcare professional collaborated in a joint quest towards a pathway to recovery. The findings underpin the importance of believing and learning from patient experience, particularly vanguard patients with new and emerging illnesses.}, } @article {pmid36505947, year = {2022}, author = {Marra, AR and Kobayashi, T and Suzuki, H and Alsuhaibani, M and Hasegawa, S and Tholany, J and Perencevich, E and Maezato, AM and Ricardo, VCV and Salinas, JL and Edmond, MB and Rizzo, LV}, title = {The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis.}, journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE}, volume = {2}, number = {1}, pages = {e192}, pmid = {36505947}, issn = {2732-494X}, abstract = {BACKGROUND: Although multiple studies have revealed that coronavirus disease 2019 (COVID-19) vaccines can reduce COVID-19-related outcomes, little is known about their impact on post-COVID-19 conditions. We performed a systematic literature review and meta-analysis on the effectiveness of COVID-19 vaccination against post-COVID-19 conditions (ie, long COVID).

METHODS: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine. A post-COVID-19 condition was defined as any symptom that was present 3 or more weeks after having COVID-19. Editorials, commentaries, reviews, study protocols, and studies in the pediatric population were excluded. We calculated the pooled diagnostic odds ratios (DORs) for post-COVID-19 conditions between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 - DOR).

RESULTS: In total, 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post-COVID-19 conditions, of which 6 studies were included in the meta-analysis. The pooled DOR for post-COVID-19 conditions among individuals vaccinated with at least 1 dose was 0.708 (95% confidence interval (CI), 0.692-0.725) with an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%-30.8%). The vaccine effectiveness was 35.3% (95% CI, 32.3%-38.1%) among those who received the COVID-19 vaccine before having COVID-19, and 27.4% (95% CI, 25.4%-29.3%) among those who received it after having COVID-19.

CONCLUSIONS: COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low.}, } @article {pmid36505604, year = {2022}, author = {Raj, SVA and Jacob, A and Ambu, V and Wilson, T and Renuka, R}, title = {Post COVID-19 clinical manifestations and its risk factors among patients in a Northern District in Kerala, India.}, journal = {Journal of family medicine and primary care}, volume = {11}, number = {9}, pages = {5312-5319}, pmid = {36505604}, issn = {2249-4863}, abstract = {BACKGROUND: The novel virus SARS-CoV-2 has caused a pandemic of coronavirus disease 2019 (COVID-19). There is emerging evidence of post-COVID-19 manifestations among patients who sustain acute COVID-19. Most studies report fatigue, dyspnea, and myalgia as the common symptoms; however, currently, there is limited knowledge of these post-COVID manifestations and their risk factors, especially in India.

METHODS: A descriptive cross-sectional study was conducted among patients who had attended the district post-COVID clinic, Wayanad district, Kerala, from October 2020 to June 2021. Data were collected by direct/telephonic patient interviews and from their existing case records, using a pretested semi-structured proforma.

RESULTS: The sample size was 667. The mean age of the study population was 45 years (standard deviation [SD]: 14.55). The majority of the population presented with dyspnea (48%), fatigue (32%), and cough (25.6%). Mental health problems were also reported in 6% of participants. The respiratory system was commonly involved (61.2%). Around one-third of the patients (36.4%) had dyspnea on exertion and 11.8% had dyspnea at rest. One-fifth of the population reported aggravation of pre-existing co-morbidity and half of the respondents had persistence of at least one symptom after 6 months. There exist statistically significant associations between identified risk factors, especially gender, increasing age, the severity of COVID-19 infection, history of tobacco/alcohol use, and co-morbidities with outcomes.

CONCLUSION: As post-COVID syndrome is a multisystem disease, integrated rehabilitation is required with targeted intervention for survivors based on their symptoms and needs.}, } @article {pmid36504922, year = {2023}, author = {Pinto Pereira, SM and Shafran, R and Nugawela, MD and Panagi, L and Hargreaves, D and Ladhani, SN and Bennett, SD and Chalder, T and Dalrymple, E and Ford, T and Heyman, I and McOwat, K and Rojas, NK and Sharma, K and Simmons, R and White, SR and Stephenson, T}, title = {Natural course of health and well-being in non-hospitalised children and young people after testing for SARS-CoV-2: a prospective follow-up study over 12 months.}, journal = {The Lancet regional health. Europe}, volume = {25}, number = {}, pages = {100554}, pmid = {36504922}, issn = {2666-7762}, support = {MC_UU_00002/2/MRC_/Medical Research Council/United Kingdom ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Despite high numbers of children and young people (CYP) having acute COVID, there has been no prospective follow-up of CYP to establish the pattern of health and well-being over a year following infection.

METHODS: A non-hospitalised, national sample of 5086 (2909 SARS-COV-2 Positive; 2177 SARS-COV-2 Negative at baseline) CYP aged 11-17 completed questionnaires 6- and 12-months after PCR-tests between October 2020 and March 2021 confirming SARS-CoV-2 infection (excluding CYP with subsequent (re)infections). SARS-COV-2 Positive CYP was compared to age, sex and geographically-matched test-negative CYP.

FINDINGS: Ten of 21 symptoms had a prevalence less than 10% at baseline, 6- and 12-months post-test in both test-positives and test-negatives. Of the other 11 symptoms, in test-positives who had these at baseline, the prevalence of all symptoms declined greatly by 12-months. For CYP first describing one of these at 6-months, there was a decline in prevalence by 12-months. The overall prevalence of 9 of 11 symptoms declined by 12-months. As many CYP first described shortness of breath and tiredness at either 6- or 12-months, the overall prevalence of these two symptoms in test-positives appeared to increase by 6-months and increase further by 12-months. However, within-individual examination demonstrated that the prevalence of shortness of breath and tiredness actually declined in those first describing these two symptoms at either baseline or 6-months. This pattern was also evident for these two symptoms in test-negatives. Similar patterns were observed for validated measures of poor quality of life, emotional and behavioural difficulties, poor well-being and fatigue. Moreover, broadly similar patterns and results were noted for the sub-sample (N = 1808) that had data at baseline, 3-, 6- and 12-months post-test.

INTERPRETATION: In CYP, the prevalence of adverse symptoms reported at the time of a positive PCR-test declined over 12-months. Some test-positives and test-negatives reported adverse symptoms for the first time at six- and 12-months post-test, particularly tiredness, shortness of breath, poor quality of life, poor well-being and fatigue suggesting they are likely to be caused by multiple factors.

FUNDING: NIHR/UKRI (ref: COVLT0022).}, } @article {pmid36503014, year = {2023}, author = {Fauveau, V and Jacobi, A and Bernheim, A and Chung, M and Benkert, T and Fayad, ZA and Feng, L}, title = {Performance of spiral UTE-MRI of the lung in post-COVID patients.}, journal = {Magnetic resonance imaging}, volume = {96}, number = {}, pages = {135-143}, pmid = {36503014}, issn = {1873-5894}, support = {R01 EB031083/EB/NIBIB NIH HHS/United States ; R21 EB032917/EB/NIBIB NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/diagnostic imaging ; Lung/diagnostic imaging/pathology ; Magnetic Resonance Imaging/methods ; Breath Holding ; Imaging, Three-Dimensional/methods ; }, abstract = {Patients recovered from COVID-19 may develop long-COVID symptoms in the lung. For this patient population (post-COVID patients), they may benefit from longitudinal, radiation-free lung MRI exams for monitoring lung lesion development and progression. The purpose of this study was to investigate the performance of a spiral ultrashort echo time MRI sequence (Spiral-VIBE-UTE) in a cohort of post-COVID patients in comparison with CT and to compare image quality obtained using different spiral MRI acquisition protocols. Lung MRI was performed in 36 post-COVID patients with different acquisition protocols, including different spiral sampling reordering schemes (line in partition or partition in line) and different breath-hold positions (inspiration or expiration). Three experienced chest radiologists independently scored all the MR images for different pulmonary structures. Lung MR images from spiral acquisition protocol that received the highest image quality scores were also compared against corresponding CT images in 27 patients for evaluating diagnostic image quality and lesion identification. Spiral-VIBE-UTE MRI acquired with the line in partition reordering scheme in an inspiratory breath-holding position achieved the highest image quality scores (score range = 2.17-3.69) compared to others (score range = 1.7-3.29). Compared to corresponding chest CT images, three readers found that 81.5% (22 out of 27), 81.5% (22 out of 27) and 37% (10 out of 27) of the MR images were useful, respectively. Meanwhile, they all agreed that MRI could identify significant lesions in the lungs. The Spiral-VIBE-UTE sequence allows for fast imaging of the lung in a single breath hold. It could be a valuable tool for lung imaging without radiation and could provide great value for managing different lung diseases including assessment of post-COVID lesions.}, } @article {pmid36502582, year = {2023}, author = {Tippett, E and Hitch, D and Irving, L and Watters, D}, title = {Post-acute COVID-19 condition (PACC): a perspective on collaborative Australian research imperatives and primary health models of care.}, journal = {Australian journal of primary health}, volume = {29}, number = {4}, pages = {293-295}, doi = {10.1071/PY22009}, pmid = {36502582}, issn = {1836-7399}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Australia/epidemiology ; Quality of Health Care ; Longitudinal Studies ; }, abstract = {Post-acute COVID-19 condition (PACC) - also known as long COVID - is a serious and growing problem in primary health. This letter describes the work of the Victorian Post-Acute COVID-19 Study (VPACS) group, which comprises clinician researchers, basic scientists and consumers. Two key priorities for PACC research in Australia are identified and discussed: (1) the establishment of COVID-19 patient registries and data linkage; and (2) the consolidation of clinical guidelines. Collaboration between consumers, researchers, clinicians and institutions must be the foundation of PACC management in Australia. Ongoing research should focus on large, multicentre controlled studies, the protective effect of vaccination, differential impacts from variants, pathobiological underpinnings, disease mechanisms to avoid severe and enduring impacts on the Australian economy. The lived experience of people with PACC is also essential to enable the design and implementation of effective models of care. VPACS brings a diverse group of people together to work on a shared vision of holistic and high-quality care, and collectively maximise their impact on outcomes for patients and the broader community.}, } @article {pmid36501014, year = {2022}, author = {Tosato, M and Calvani, R and Picca, A and Ciciarello, F and Galluzzo, V and Coelho-Júnior, HJ and Di Giorgio, A and Di Mario, C and Gervasoni, J and Gremese, E and Leone, PM and Nesci, A and Paglionico, AM and Santoliquido, A and Santoro, L and Santucci, L and Tolusso, B and Urbani, A and Marini, F and Marzetti, E and Landi, F and , }, title = {Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.}, journal = {Nutrients}, volume = {14}, number = {23}, pages = {}, pmid = {36501014}, issn = {2072-6643}, mesh = {Adult ; Humans ; Female ; Young Adult ; Middle Aged ; Male ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Hand Strength ; Ascorbic Acid/therapeutic use ; Single-Blind Method ; Double-Blind Method ; Vitamins ; Arginine/therapeutic use ; Physical Functional Performance ; Fatigue/drug therapy/etiology ; }, abstract = {Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.}, } @article {pmid36499711, year = {2022}, author = {Singh, S and Yang, YF}, title = {Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36499711}, issn = {1422-0067}, mesh = {Humans ; Animals ; Mice ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; Network Pharmacology ; Medicine, Chinese Traditional ; Tumor Necrosis Factor-alpha ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Molecular Docking Simulation ; }, abstract = {Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches. Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals. Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments. In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.}, } @article {pmid36498197, year = {2022}, author = {Thronicke, A and Hinse, M and Weinert, S and Jakubowski, A and Grieb, G and Matthes, H}, title = {Factors Associated with Self-Reported Post/Long-COVID-A Real-World Data Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498197}, issn = {1660-4601}, support = {n.a.//Software AG (Italy)/ ; }, mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology ; Self Report ; Depression ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; Fatigue/epidemiology ; }, abstract = {Evidence suggests that Post/Long-COVID (PLC) is associated with a reduced health-related quality of life, however little knowledge exists on the risk factors that contribute to PLC. The objective of this prospective real-world data study was to evaluate factors associated with PLC using national online survey data. Adjusted multivariable regression analyses were performed using the software R. Between 14 April and 15 June 2021, 99 registered individuals reported to have suffered from PLC symptoms and the most common PLC symptoms reported were fatigue, dyspnoea, decreased strength, hyposmia, and memory loss. The odds of individuals suffering from COVID-19-associated anxiety, hyposmia, or heart palpitations developing PLC were eight times (OR 8.28, 95% CI 1.43−47.85, p < 0.01), five times (OR 4.74, 95% CI 1.59−14.12, p < 0.005), or three times (OR 2.62, 95% CI 1.72−3.99, p < 0.01) higher, respectively, than of those who had not experienced these symptoms. Individuals who experienced fatigue while having COVID-19 were seven times more likely to develop PLC fatigue than those who had not (OR 6.52, 95% CI: 4.29−9.91, p < 0.0001). Our findings revealed that 13% of the individuals who had previously suffered from COVID-19 subsequently reported having PLC. Furthermore, COVID-19-associated anxiety, hyposmia, heart palpitations, and fatigue were, among others, significant determinants for the development of PLC symptoms. Hyposmia has not previously been reported as an independent predictive factor for PLC. We suggest closely monitoring patients with COVID-19-induced fatigue, heart palpitations, and anxiety, as these symptoms may be predictors of PLC symptoms, including fatigue.}, } @article {pmid36498103, year = {2022}, author = {Du, M and Ma, Y and Deng, J and Liu, M and Liu, J}, title = {Comparison of Long COVID-19 Caused by Different SARS-CoV-2 Strains: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498103}, issn = {1660-4601}, support = {72122001, 71934002//National Natural Science Foundation of China/ ; 2021ZD0114101, 2021ZD0114104, 2021ZD0114105//National Key Research and Development Project of China/ ; 2021LY038//National Statistical Science Research Project/ ; 202204/WT_/Wellcome Trust/United Kingdom ; KY202101004//National Science and Technology Project on Development Assistance for Technology, Developing China-ASEAN Public Health Research and Development Collaborating Center/ ; }, mesh = {Humans ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Pandemics ; Fatigue/epidemiology ; *Sleep Wake Disorders ; }, abstract = {Although many studies of long COVID-19 were reported, there was a lack of systematic research which assessed the differences of long COVID-19 in regard to what unique SARS-CoV-2 strains caused it. As such, this systematic review and meta-analysis aims to evaluate the characteristics of long COVID-19 that is caused by different SARS-CoV-2 strains. We systematically searched the PubMed, EMBASE, and ScienceDirect databases in order to find cohort studies of long COVID-19 as defined by the WHO (Geneva, Switzerland). The main outcomes were in determining the percentages of long COVID-19 among patients who were infected with different SARS-CoV-2 strains. Further, this study was registered in PROSPERO (CRD42022339964). A total of 51 studies with 33,573 patients was included, of which three studies possessed the Alpha and Delta variants, and five studies possessed the Omicron variant. The highest pooled estimate of long COVID-19 was found in the CT abnormalities (60.5%; 95% CI: 40.4%, 80.6%) for the wild-type strain; fatigue (66.1%; 95% CI: 42.2%, 89.9%) for the Alpha variant; and ≥1 general symptoms (28.4%; 95% CI: 7.9%, 49.0%) for the Omicron variant. The pooled estimates of ≥1 general symptoms (65.8%; 95% CI: 47.7%, 83.9%) and fatigue were the highest symptoms found among patients infected with the Alpha variant, followed by the wild-type strain, and then the Omicron variant. The pooled estimate of myalgia was highest among patients infected with the Omicron variant (11.7%; 95%: 8.3%, 15.1%), compared with those infected with the wild-type strain (9.4%; 95%: 6.3%, 12.5%). The pooled estimate of sleep difficulty was lowest among the patients infected with the Delta variant (2.5%; 95%: 0.2%, 4.9%) when compared with those infected with the wild-type strain (24.5%; 95%: 17.5%, 31.5%) and the Omicron variant (18.7%; 95%: 1.0%, 36.5%). The findings of this study suggest that there is no significant difference between long COVID-19 that has been caused by different strains, except in certain general symptoms (i.e., in the Alpha or Omicron variant) and in sleep difficulty (i.e., the wild-type strain). In the context of the ongoing COVID-19 pandemic and its emerging variants, directing more attention to long COVID-19 that is caused by unique strains, as well as implementing targeted intervention measures to address it are vital.}, } @article {pmid36498091, year = {2022}, author = {Fischer, A and Badier, N and Zhang, L and Elbéji, A and Wilmes, P and Oustric, P and Benoy, C and Ollert, M and Fagherazzi, G}, title = {Long COVID Classification: Findings from a Clustering Analysis in the Predi-COVID Cohort Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36498091}, issn = {1660-4601}, support = {14716273//Luxembourg National Research Fund (FNR)/ ; }, mesh = {Humans ; Female ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Quality of Life ; }, abstract = {The increasing number of people living with Long COVID requires the development of more personalized care; currently, limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratify people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified three patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean = 2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and poor sleep and respiratory quality of life. Compared to the other clusters, Cluster-Severe was characterized by a higher proportion of women and smokers with a higher number of Long COVID symptoms, in particular vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified into three subcategories in terms of severity. If replicated in other populations, this simple classification will help clinicians improve the care of people with Long COVID.}, } @article {pmid36497744, year = {2022}, author = {Wu, X and Yong, CC and Lee, ST}, title = {Addressing the COVID-19 Shock: The Potential Job Creation in China by the RCEP.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36497744}, issn = {1660-4601}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Employment ; *COVID-19/epidemiology ; China/epidemiology ; }, abstract = {In 2020, coronavirus disease (COVID-19) left around 81% of the global workforce, nearly 2.7 billion workers, affected. Employment in China was the first to be hit by COVID-19. The Regional Comprehensive Economic Partnership (RCEP) is expected to bring dynamism to China's employment market in an era of long COVID-19. This study aims to examine the number of sectoral jobs that the RCEP will create in China, with the number of skilled or unskilled labour employed in each sector. The exogenous shocks to the RCEP can be reflected in the number of jobs created through multipliers based on a social accounting matrix compiled from China's input-output tables in 2017, combined with the employment satellite accounts compiled. The results show that the RCEP is expected to create over 17 million potential jobs in China, with unskilled labour accounting for 10.44 million and skilled labour for 6.77 million. It is even expected that there will be job losses in the metalworking machinery sector. The contribution of this paper can serve as a reference for policies to protect vulnerable sectors, further open up trade markets and strengthen cooperation among RCEP members as important measures to address the employment impact of long COVID-19.}, } @article {pmid36497573, year = {2022}, author = {Chasco, EE and Dukes, K and Jones, D and Comellas, AP and Hoffman, RM and Garg, A}, title = {Brain Fog and Fatigue following COVID-19 Infection: An Exploratory Study of Patient Experiences of Long COVID.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {23}, pages = {}, pmid = {36497573}, issn = {1660-4601}, support = {P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Quality of Life ; Mental Fatigue ; Fatigue/etiology ; Disease Progression ; Patient Outcome Assessment ; Brain ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC) is a poorly understood condition with significant impact on quality of life. We aimed to better understand the lived experiences of patients with PASC, focusing on the impact of cognitive complaints ("brain fog") and fatigue on (1) daily activities, (2) work/employment, and (3) interpersonal relationships. We conducted semi-structured qualitative interviews with 15 patients of a Midwestern academic hospital's post-COVID-19 clinic. We audio-recorded, transcribed, and analyzed interviews thematically using a combined deductive-inductive approach and collected participants' characteristics from chart review. Participants frequently used descriptive and metaphorical language to describe symptoms that were relapsing-remitting and unpredictable. Fatigue and brain fog affected all domains and identified subthemes included symptoms' synergistic effects, difficulty with multitasking, lack of support, poor self-perception, and fear of loss of income and employment. Personal relationships were affected with change of responsibilities, difficulty parenting, social isolation, and guilt due to the burdens placed on family. Furthermore, underlying social stigma contributed to negative emotions, which significantly affected emotional and mental health. Our findings highlight PASC's negative impact on patients' daily lives. Providers can better support COVID-19 survivors during their recovery by identifying their needs in a sensitive and timely manner.}, } @article {pmid36497138, year = {2022}, author = {Kobusiak-Prokopowicz, M and Fułek, K and Fułek, M and Kaaz, K and Mysiak, A and Kurpas, D and Beszłej, JA and Brzecka, A and Leszek, J}, title = {Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19.}, journal = {Cells}, volume = {11}, number = {23}, pages = {}, pmid = {36497138}, issn = {2073-4409}, mesh = {Humans ; *COVID-19/complications ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Lung ; }, abstract = {Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.}, } @article {pmid36496499, year = {2022}, author = {Bartczak, KT and Milkowska-Dymanowska, J and Piotrowski, WJ and Bialas, AJ}, title = {The utility of telemedicine in managing patients after COVID-19.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {21392}, pmid = {36496499}, issn = {2045-2322}, mesh = {Humans ; Middle Aged ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Pandemics/prevention & control ; }, abstract = {Despite growing knowledge about transmission and relatively wide access to prophylaxis, the world is still facing a severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) global pandemic. Under these circumstances telemedicine emerges as a powerful tool for safe at-home surveillance after a hospital discharge; the data on when to safely release a patient after acute COVID-19 is scarce. Reckoning an urgent need for improving outpatient management and possibly fatal complications of the post-COVID period, we performed the pilot telemonitoring program described below. The study aimed to assess the usefulness of parameters and surveys remotely obtained from COVID-19 convalescents in their individual prognosis prediction. Patients were involved in the study between December 2020 and May 2021. Recruitment was performed either during the hospital discharge (those hospitalized in a Barlicki Memorial Hospital in Lodz) or the first outpatient visit up to 6 weeks after discharge from another center. Every participant received equipment for daily saturation and heart rate measurement coupled with a tablet for remote data transmission. The measurements were made after at least fifteen minutes of rest in a sitting position without oxygen supplementation. Along with the measurements, the cough and dyspnea daily surveys (1-5 points) and Fatigue Assessment Scale weekly surveys were filled. We expected a saturation decrease during thromboembolic events, infectious complications, etc. A total of 30 patients were monitored for a minimum period of 45 days, at least 2 weeks after spontaneous saturation normalization. The mean age was 55 (mean 55.23; SD ± 10.64 years). The group was divided according to clinical improvement defined as the ≥ 10% functional vital capacity (FVC) raise or ≥ 15% lung transfer for carbon monoxide (TL,CO) rise. Our findings suggest that at-rest home saturation measurements below 94% (p = 0.03) correspond with the lack of clinical improvement in post-COVID observation (p = 0.03). The non-improvement group presented with a lower mean-94 (93-96)% versus 96 (95-97)%, p = 0.01 and minimum saturation-89 (86-92)% versus 92 (90-94)%, p = 0.04. They also presented higher variations in saturation measurements; saturation amplitude was 9 (7-11)% versus 7 (4-8)%, p = 0.03; up to day 22 most of the saturation differences reached statistical significance. Last but not least, we discovered that participants missing 2 or more measurements during the observation were more often ranked into the clinical improvement group (p = 0.01). Heart rate day-to-day measurements did not differ between both groups; gathered data about dyspnea and cough intensity did not reach statistical significance either. A better understanding of the disease's natural history will ultimately lead us to a better understanding of long COVID symptoms and corresponding threats. In this paper, we have found home oxygen saturation telemonitoring to be useful in the prediction of the trajectory of the disease course. Our findings suggest that detection of at-rest home saturation measurement equal to or below 94% corresponds with the lack of clinical improvement at the time of observation and this group of patients presented higher variability of day-to-day oxygen saturation measurements. The determination of which patient should be involved in telemedicine programs after discharge requests further research.}, } @article {pmid36496030, year = {2023}, author = {Harding, JL and Oviedo, SA and Ali, MK and Ofotokun, I and Gander, JC and Patel, SA and Magliano, DJ and Patzer, RE}, title = {The bidirectional association between diabetes and long-COVID-19 - A systematic review.}, journal = {Diabetes research and clinical practice}, volume = {195}, number = {}, pages = {110202}, pmid = {36496030}, issn = {1872-8227}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus/epidemiology ; Risk Factors ; Disease Progression ; }, abstract = {Some evidence suggests that diabetes may be a risk factor for the development of post-acute sequelae of COVID-19 (PASC). Recent data also indicate that new-onset diabetes may be a complication of COVID-19. Here, we review the existing evidence. Following PRISMA guidelines, we conducted a systematic review through August 8, 2022. We included longitudinal studies reporting on the risk of PASC (i.e., sequelae that extend beyond four weeks after initial infection) in people with and without diabetes, and studies reporting on the risk of new-onset diabetes in people with vs without COVID-19 with a minimum of 4-weeks of follow-up. All studies were published in English. Among 5,532 studies screened, 39 were included in the final review. Among 25 studies reporting on diabetes and PASC, 44 % (n = 11) identified diabetes as a significant risk factor for PASC (increased relative risk ranging from 7 % to 342 %) while 56 % (n = 14) did not. Among 14 studies reporting on new-onset diabetes, 12 (86 %) reported that COVID-19 (vs no COVID) was significantly associated with new-onset diabetes with increased risks ranging from 11 % to 276 %. COVID-19 survivors may be at increased risk for new-onset diabetes, but whether pre-existing diabetes is also a risk factor for PASC remains unclear.}, } @article {pmid36494763, year = {2022}, author = {Khalife, J}, title = {Effective strategies against COVID-19 and the importance of infection sequelae.}, journal = {Global health research and policy}, volume = {7}, number = {1}, pages = {49}, pmid = {36494763}, issn = {2397-0642}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics/prevention & control ; }, abstract = {COVID-19 is a serious threat to human health and development. The acute burden of the pandemic includes more than 18.2 million deaths worldwide, and is unprecedented in modern times. This represents only a fraction of the total burden, as it excludes infection sequelae. An effective global strategic paradigm has been missing throughout the pandemic. The 'flattening the curve' approach neglected the importance of infection sequelae, and being centered on healthcare capacity was conceptually contrary to a people-centered health system. In March 2022, the World Health Organization revised its pandemic approach, importantly shifting emphasis away from managing transmission and towards prevention. Despite limitations, this now recognizes the role of infection sequelae, whose impact is becoming clearer in both variety and scale. Drawing on the foundational concepts of Sun Tzu and Carl von Clausewitz, most country approaches do not qualify as strategies, but rather as operational plans. They are also largely ineffective, neglecting infection sequelae, viral evolution dangers and other parameters. The purpose of this article is to summarize the evidence on COVID-19 infection sequelae, and alongside other contextual parameters use this to motivate that infection should be prevented. This is then used to answer the question: What is an effective strategy against COVID-19?}, } @article {pmid36494289, year = {2023}, author = {Sher, L}, title = {Long COVID and the risk of suicide.}, journal = {General hospital psychiatry}, volume = {80}, number = {}, pages = {66-67}, pmid = {36494289}, issn = {1873-7714}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Suicide ; SARS-CoV-2 ; }, } @article {pmid36483107, year = {2022}, author = {Swarnakar, R and Jenifa, S and Wadhwa, S}, title = {Musculoskeletal complications in long COVID-19: A systematic review.}, journal = {World journal of virology}, volume = {11}, number = {6}, pages = {485-495}, pmid = {36483107}, issn = {2220-3249}, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has crippled humanity since early 2020. Various sequelae of COVID-19 have been reported in different body systems. Musculoskeletal symptoms are widely reported during COVID-19 infection, but musculoskeletal complications in long COVID-19 are underreported. However, post-COVID-19 survivors have reported complaints of persisting or new-onset fatigue, myalgia, arthralgia, arthritis, muscle weakness, etc in clinical practice. The well-known detrimental effects of steroids on the musculoskeletal system coupled with their over-the-counter availability can also be anticipated since they were the cornerstone of life-saving management in this pandemic.

AIM: To determine the musculoskeletal complications in long COVID.

METHODS: We performed a systematic review of 'systematic reviews and meta-analyses'.

RESULTS: Of the 63 articles screened, 24 articles were included. Two articles specifically discussed children and adolescents. One article discussed rehabilitation intervention. No article addressed rehabilitation of musculoskeletal issues in long COVID-19 in particular. Fatigue was the most common musculoskeletal complication.

CONCLUSION: Fatigue is found to be very common along with myalgia and arthralgia. There were no studies on rehabilitation intervention in musculoskeletal complications specifically. Considering the lacuna in literature and the needs of the current situation, further studies are warranted to standardize effective rehabilitation interventions in musculoskeletal complications. More homogenous studies are needed. Studies on functional impairment due to musculoskeletal involvement are essential.}, } @article {pmid36482164, year = {2023}, author = {Gudziol, H and Bitter, T and Kirschstein, T and Laute, K and Schade, U and Guntinas-Lichius, O}, title = {[Reported and measured olfactory and gustatory findings in a long-COVID cohort].}, journal = {Laryngo- rhino- otologie}, volume = {102}, number = {3}, pages = {194-202}, doi = {10.1055/a-1970-6510}, pmid = {36482164}, issn = {1438-8685}, mesh = {Adult ; Humans ; Smell ; Taste ; *Olfaction Disorders/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; }, abstract = {INTRODUCTION: Disorders of the sense of smell and taste are often complained as a long-COVID symptom. In a special long-COVID consultation (ENT-LCS), we wanted to figure out how large the proportion of pathological olfactory or gustatory diagnoses actually is in this cohort.

METHODS: 48 adult patients who visited the ENT-LCS because of their own suffering were asked about their history, rated their ability to smell (SER) and taste (SES) with school grades and completed the extended Sniffin' Sticks test and the 3-drop test as a taste test. Diagnoses were made from the SDI smell score and the total taste score using normative values. Correlations were calculated between the measured scores and the self-assessment and between SER and SES.

RESULTS: Pathological chemosensory diagnoses were present in 90%. Pathological olfactory diagnoses were twice as common as gustatory ones. No pathological diagnosis could be verified in 10% of the cohort. Anosmia-ageusia syndrome was diagnosed in six patients. SER correlated strongly with SDI. SES correlated moderately with SScore-total. SER correlated strongly with SES.

CONCLUSIONS: There is a risk of smell-taste confusion when interpreting reported chemosensory symptoms. This is another reason why reference is made to the importance of quantifying the chemical senses with validated tests.}, } @article {pmid36480981, year = {2022}, author = {Mansell, V and Hall Dykgraaf, S and Kidd, M and Goodyear-Smith, F}, title = {Long COVID and older people.}, journal = {The lancet. Healthy longevity}, volume = {3}, number = {12}, pages = {e849-e854}, doi = {10.1016/S2666-7568(22)00245-8}, pmid = {36480981}, issn = {2666-7568}, mesh = {Humans ; Aged ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; COVID-19 Vaccines ; Quality of Life ; Communicable Disease Control ; }, abstract = {Long COVID is a poorly understood condition, with a wide spectrum of effects on multiple body systems and variable presentation in different individuals. Long COVID is of particular concern among older people (ie, aged 65 years or older), who are at greater risk than younger people of persisting symptoms associated with COVID-19. In addition, COVID-19 might trigger or exacerbate chronic conditions that occur commonly in older people, such as cardiovascular diseases, respiratory diseases, neurodegenerative conditions, and functional decline. In addition, the disruptive effects of COVID-19 for older people should not be underestimated; lockdowns and other restrictions might have reduced the social interactions of older people, and they are also likely to have lost a spouse or loved one during the pandemic, which can contribute to mental and physical decline. COVID-19 vaccination appears to reduce the effects of long COVID, and older people, especially those living in aged care facilities, should remain up-to-date with their COVID-19 vaccinations. Health-care staff should also consider long COVID in the differential diagnosis of relevant symptoms in older people, rather than assume increasing frailty, and should pursue early multidisciplinary assessment and management of persisting symptoms. Addressing physical, psychological, and functional sequelae will mitigate the effect of long COVID and improve the health and quality of life of older people.}, } @article {pmid36480262, year = {2024}, author = {Kohn, L and Dauvrin, M and Detollenaere, J and Primus-de Jong, C and Maertens de Noordhout, C and Castanares-Zapatero, D and Cleemput, I and Van den Heede, K}, title = {Long COVID and return to work: a qualitative study.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {29-36}, doi = {10.1093/occmed/kqac119}, pmid = {36480262}, issn = {1471-8405}, support = {//Belgian Health Care Knowledge Centre/ ; }, mesh = {Humans ; *Return to Work/psychology ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19 ; SARS-CoV-2 ; Qualitative Research ; }, abstract = {BACKGROUND: The COVID-19 pandemic has given rise to an increasing number of patients with 'long COVID'. Long COVID is the persistence of symptoms for weeks or months after an infection by SARS-CoV-2. It often impacts on the professional life of affected people.

AIMS: The aim of this study is to understand the experiences and needs of people with long COVID in relation to their return to work.

METHODS: A qualitative study, combining individual interviews and online forum discussions, was performed early 2021, as part of a larger mixed method study on the needs of long COVID patients in Belgium.

RESULTS: One hundred and thirty-four people participated in the study. Participants described various clinical symptoms precluding their return to work. They also face sceptical reactions from employers and colleagues and a lack of support from the social welfare system to facilitate their return to work. These barriers have various impacts, including psychological ones, likely to compromise the professional future of long COVID patients.

CONCLUSIONS: While the analysis of patients' experiences shows variation in long COVID patients' experiences with return to work, it may help occupational physicians and healthcare practitioners to better take up their crucial role in the return to work of long COVID patients, including raising employers' and colleagues' awareness of the specific difficulties related to long COVID.}, } @article {pmid36479948, year = {2023}, author = {Gokani, SA and Ta, NH and Espehana, A and Garden, EM and Klyvyte, G and Luke, L and Myuran, T and Uththerakunaseelan, V and Boak, DC and Philpott, CM}, title = {The growing burden of long COVID in the United Kingdom: Insights from the UK Coronavirus Infection Survey.}, journal = {International forum of allergy & rhinology}, volume = {13}, number = {8}, pages = {1535-1538}, pmid = {36479948}, issn = {2042-6984}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Taste Disorders ; United Kingdom/epidemiology ; *Olfaction Disorders ; Smell ; Taste ; }, } @article {pmid36479679, year = {2022}, author = {Koczulla, AR and Ankermann, T and Behrends, U and Berlit, P and Berner, R and Böing, S and Brinkmann, F and Frank, U and Franke, C and Glöckl, R and Gogoll, C and Häuser, W and Hohberger, B and Huber, G and Hummel, T and Köllner, V and Krause, S and Kronsbein, J and Maibaum, T and Otto-Thöne, A and Pecks, U and Peters, EMJ and Peters, S and Pfeifer, M and Platz, T and Pletz, M and Powitz, F and Rabe, KF and Scheibenbogen, C and Schneider, D and Stallmach, A and Stegbauer, M and Tenenbaum, T and Töpfner, N and von Versen-Höynck, F and Wagner, HO and Waller, C and Widmann, CN and Winterholler, C and Wirtz, H and Zwick, R}, title = {[German S1 Guideline Long-/Post-COVID].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {76}, number = {12}, pages = {855-907}, doi = {10.1055/a-1946-3230}, pmid = {36479679}, issn = {1438-8790}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, abstract = {The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.}, } @article {pmid36479046, year = {2022}, author = {Haider, HF and Szczepek, AJ}, title = {Editorial: Neurotological consequences of long COVID.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1087896}, pmid = {36479046}, issn = {1664-2295}, } @article {pmid36477364, year = {2023}, author = {van der Maaden, T and Mutubuki, EN and de Bruijn, S and Leung, KY and Knoop, H and Slootweg, J and Tulen, AD and Wong, A and van Hoek, AJ and Franz, E and van den Wijngaard, CC}, title = {Prevalence and Severity of Symptoms 3 Months After Infection With SARS-CoV-2 Compared to Test-Negative and Population Controls in the Netherlands.}, journal = {The Journal of infectious diseases}, volume = {227}, number = {9}, pages = {1059-1067}, doi = {10.1093/infdis/jiac474}, pmid = {36477364}, issn = {1537-6613}, mesh = {Humans ; *SARS-CoV-2 ; Netherlands/epidemiology ; *COVID-19/epidemiology ; Anosmia ; Population Control ; Prevalence ; Prospective Studies ; }, abstract = {BACKGROUND: This prospective study assesses symptoms 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared to test-negative and population controls, and the effect of vaccination prior to infection.

METHODS: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2 test, or after invitation from the general population (population controls). After 3 months, participants indicated presence of 41 symptoms and severity of 4 symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection.

RESULTS: In total, 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At 3 months, 13 symptoms, and severity of fatigue, cognitive impairment, and dyspnea were significantly elevated incases compared to controls. Of cases, 48.5% reported ≥1 significantly elevated symptom compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases aged <65 years, and was significantly protective for loss of smell and taste but not for other symptoms.

DISCUSSION: Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which was higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65 years.}, } @article {pmid36476156, year = {2023}, author = {Jimeno-Almazán, A and Buendía-Romero, Á and Martínez-Cava, A and Franco-López, F and Sánchez-Alcaraz, BJ and Courel-Ibáñez, J and Pallarés, JG}, title = {Effects of a concurrent training, respiratory muscle exercise, and self-management recommendations on recovery from post-COVID-19 conditions: the RECOVE trial.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {134}, number = {1}, pages = {95-104}, pmid = {36476156}, issn = {1522-1601}, mesh = {Adult ; Humans ; Quality of Life ; *Self-Management ; *COVID-19 ; Exercise/physiology ; Respiratory Muscles/physiology ; Muscle Strength/physiology ; Breathing Exercises ; Fatigue ; }, abstract = {The aim of this study was to determine the effectiveness of physical exercise, respiratory muscle training, and the self-management World Health Organization (WHO) recommendations leaflet on the recovery of physical fitness, quality of life, and symptom status in people with post-COVID-19 conditions. Eighty nonhospitalized adults with a post-COVID-19 condition were randomly assigned to one of four 8-wk parallel intervention groups: 1) multicomponent exercise program based on concurrent training (CT, number of subjects (n) = 20; 3 resistance and endurance supervised sessions per week at low-moderate intensity); 2) inspiratory muscle training (RM, n = 17; 2 standardized daily sessions); 3) a combination of both of the above (CTRM, n = 23); and 4) control group (CON, n = 20; following the WHO guidelines for post-COVID-19-related illness rehabilitation). No significant differences between groups were detected at baseline. Although no significant differences between interventions were detected in the V̇o2max, significant individual improvements were identified in the CT (7.5%; effect size, ES = 0.28) and CTRM (7.8%; ES = 0.36) groups. Lower body muscle strength significantly improved in the CT and CTRM (14.5%-32.6%; ES = 0.27-1.13) groups compared with RM and CON (-0.3% to 11.3%; ES = 0.10-0.19). The CT and CTRM groups improved significantly for dyspnea and fatigue, as did the health status. In addition, significant differences between interventions were described in fatigue and depression scales favoring CT and CTRM interventions. An individualized and supervised concurrent training with or without inspiratory muscle training was safe and more effective than self-care recommendations and inspiratory muscle training alone, to regain cardiovascular and muscular fitness, improve symptom severity, and health status in outpatients with post-COVID-19 conditions.NEW & NOTEWORTHY Eight weeks of concurrent training, with or without inspiratory muscle exercise, was better than WHO "Support for Rehabilitation: Self-Management after COVID-19-Related Illness" recommendations or inspiratory muscle training alone to improve cardiopulmonary fitness, strength, and symptom severity, in a safe and effective manner. The RECOVE trial proved the benefits and utility of a supervised exercise program in people with post-COVID-19 conditions after mild COVID-19 in an ambulatory setting.}, } @article {pmid36476088, year = {2022}, author = {Tullie, S and Michell, A and Reid, AWN}, title = {Bilateral Carpal Tunnel Syndrome Following COVID-19 Vaccination: A Case Report.}, journal = {The journal of hand surgery Asian-Pacific volume}, volume = {27}, number = {6}, pages = {1035-1037}, doi = {10.1142/S242483552272050X}, pmid = {36476088}, issn = {2424-8363}, mesh = {*COVID-19 Vaccines/adverse effects ; Immunization, Secondary ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control ; ChAdOx1 nCoV-19 ; *Carpal Tunnel Syndrome/surgery ; Median Nerve ; }, abstract = {Coronavirus disease 2019 (COVID-19) continues to pose significant health challenges, with insights into long-term disease sequelae emerging. The post-viral effects resulting from COVID-19 are being investigated and 'long COVID-19' is now a recognised phenomenon. As part of the spectrum of comorbidities, acute-onset neuropathy is associated with infection. The public health response aimed at limiting morbidity and mortality is rooted in vaccination programmes. With the extensive roll-out of novel vaccinations, there has been careful monitoring of temporally associated health problems. Some of the documented associations include neuropathy and entrapment neuropathies. This case report details a patient presenting with bilateral carpal tunnel syndrome (CTS) post their second dose of AZD1222 (ChAdOx1 nCoV-19) vaccination. Though we do not claim causality, the emerging post-vaccination immune-mediated effects may ultimately be proven to include neuropathy exacerbation. Meticulous recording of such associations is required as it is of great relevance to the hand surgeon managing CTS. Level of Evidence: Level V (Therapeutic).}, } @article {pmid36475055, year = {2023}, author = {Kerbl, R}, title = {[How frequent is long COVID really?].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {171}, number = {1}, pages = {3-4}, doi = {10.1007/s00112-022-01660-z}, pmid = {36475055}, issn = {0026-9298}, } @article {pmid36474804, year = {2023}, author = {O'Mahoney, LL and Routen, A and Gillies, C and Ekezie, W and Welford, A and Zhang, A and Karamchandani, U and Simms-Williams, N and Cassambai, S and Ardavani, A and Wilkinson, TJ and Hawthorne, G and Curtis, F and Kingsnorth, AP and Almaqhawi, A and Ward, T and Ayoubkhani, D and Banerjee, A and Calvert, M and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Evans, RA and Zaccardi, F and Wright, S and Khunti, K}, title = {The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis.}, journal = {EClinicalMedicine}, volume = {55}, number = {}, pages = {101762}, pmid = {36474804}, issn = {2589-5370}, support = {MC_PC_20049/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population.

METHODS: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247).

FINDINGS: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%).

INTERPRETATION: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies.

FUNDING: No funding.}, } @article {pmid36474113, year = {2023}, author = {Garai, R and Krivácsy, P and Herczeg, V and Kovács, F and Tél, B and Kelemen, J and Máthé, A and Zsáry, E and Takács, J and Veres, DS and Szabó, AJ}, title = {Clinical assessment of children with long COVID syndrome.}, journal = {Pediatric research}, volume = {93}, number = {6}, pages = {1616-1625}, pmid = {36474113}, issn = {1530-0447}, mesh = {Humans ; Child ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; *COVID-19/diagnosis ; Pandemics ; }, abstract = {BACKGROUND: There is a need for further understanding pediatric long COVID syndrome (LCS) to be able to create specific case definitions and guidelines for providing good clinical care.

METHODS: Medical records of all LCS patients who presented at our designated LC clinic were collected. We carried out descriptive analyses summarizing the history, clinical presentation, and findings of children, while doing a diagnosis of exclusion with multi-disciplinary medical examinations (physical, laboratory, and radiological examinations, specialist consultations, etc.) without a control group.

RESULTS: Most children reported at least minor impairment to their quality of life, of which 17 (23%) had moderate or severe difficulties. Findings that could be directly connected to the linked complaint category were observed in an average of 18%, respiratory symptoms with objective alterations being the most frequent (37%). Despite our detecting mostly non-specific conditions, in a smaller number we identified well-described causes such as autoimmune thyroiditis (7%).

CONCLUSIONS: The majority of children stated an impairment in their quality of life, while symptom-related conditions were detected only in a minority. Controlled studies are needed to separate the effect of the pandemic era from the infection itself. Evidence-based pediatric guidelines could aid to rationalize the list of recommended examinations.

IMPACT: Long COVID syndrome is a complex entity with a great impact on children's everyday lives. Still, there is no clear guidance for pediatric clinical management. Systematic, detailed studies with medical assessment findings could aid the process of creating evidence-based guidelines. We present validated systematic information collected during in-person medical assessments with detailed medical findings and quality of life changes. While making a diagnosis of exclusion, we could confirm symptom-related conditions only in a minority of children; however, the majority reported at least minor impairment to their quality of life.}, } @article {pmid36473651, year = {2022}, author = {Graña, C and Ghosn, L and Evrenoglou, T and Jarde, A and Minozzi, S and Bergman, H and Buckley, BS and Probyn, K and Villanueva, G and Henschke, N and Bonnet, H and Assi, R and Menon, S and Marti, M and Devane, D and Mallon, P and Lelievre, JD and Askie, LM and Kredo, T and Ferrand, G and Davidson, M and Riveros, C and Tovey, D and Meerpohl, JJ and Grasselli, G and Rada, G and Hróbjartsson, A and Ravaud, P and Chaimani, A and Boutron, I}, title = {Efficacy and safety of COVID-19 vaccines.}, journal = {The Cochrane database of systematic reviews}, volume = {12}, number = {12}, pages = {CD015477}, pmid = {36473651}, issn = {1469-493X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; Middle Aged ; Aged ; Adolescent ; *2019-nCoV Vaccine mRNA-1273 ; *COVID-19/prevention & control ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.

SEARCH METHODS: We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.

SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes.  We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs).  MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available.  This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.

AUTHORS' CONCLUSIONS: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.}, } @article {pmid36473347, year = {2023}, author = {Diana, L and Regazzoni, R and Sozzi, M and Piconi, S and Borghesi, L and Lazzaroni, E and Basilico, P and Aliprandi, A and Bolognini, N and Bonardi, DR and Colombo, D and Salmaggi, A}, title = {Monitoring cognitive and psychological alterations in COVID-19 patients: A longitudinal neuropsychological study.}, journal = {Journal of the neurological sciences}, volume = {444}, number = {}, pages = {120511}, pmid = {36473347}, issn = {1878-5883}, mesh = {Humans ; Quality of Life ; Cross-Sectional Studies ; *COVID-19/complications ; SARS-CoV-2 ; *Cognitive Dysfunction/epidemiology/etiology ; Neuropsychological Tests ; Cognition ; }, abstract = {BACKGROUND: SARS-COV-2 infection has been associated to long-lasting neuropsychiatric sequelae, including cognitive deficits, that persist after one year. However, longitudinal monitoring has been scarcely performed. Here, in a sample of COVID-19 patients, we monitor cognitive, psychological and quality of life-related profiles up to 22 months from resolution of respiratory disease.

METHODS: Out of 657 COVID-19 patients screened at Manzoni Hospital (Lecco, Italy), 22 underwent neuropsychological testing because of subjective cognitive disturbances at 6 months, 16 months, and 22 months. Tests of memory, attention, and executive functions were administered, along with questionnaires for depressive and Post-traumatic stress disorder (PTSD) symptoms, psychological well-being and quality of life. Cross-sectional descriptives, correlational, as well as longitudinal analyses considering COVID19-severity were carried out. A preliminary comparison with a sample of obstructive sleep apneas patients was also performed.

RESULTS: Around 50% of COVID-19 patients presented with cognitive deficits at t0. The most affected domain was verbal memory. Pathological scores diminished over time, but a high rate of borderline scores was still observable. Longitudinal analyses highlighted improvements in verbal and non-verbal long term memory, as well as attention, and executive functioning. Depression and PTSD-related symptoms were present in 30% of patients. The latter decreased over time and were associated to attentional-executive performance.

CONCLUSIONS: Cognitive dysfunctions in COVID-19 patients may extend over 1 year, yet showing a significant recovery in several cases. Cognitive alterations are accompanied by a significant psychological distress. Many patients displaying borderline scores, especially those at higher risk of dementia, deserve clinical monitoring.}, } @article {pmid36472878, year = {2022}, author = {Stephenson, J}, title = {Report on Long COVID Urges Actions to Address Needs of Patients, Caregivers.}, journal = {JAMA health forum}, volume = {3}, number = {12}, pages = {e225254}, doi = {10.1001/jamahealthforum.2022.5254}, pmid = {36472878}, issn = {2689-0186}, mesh = {Humans ; Caregivers ; *COVID-19 ; Patients ; *Post-Acute COVID-19 Syndrome ; }, } @article {pmid36472284, year = {2022}, author = {Ternushchak, TM and Tovt-Korshynska, MI and Varvarynets, AV}, title = {AMBULATORY BLOOD PRESSURE VARIABILITY IN YOUNG ADULTS WITH LONG-COVID SYNDROME.}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {75}, number = {10}, pages = {2481-2485}, doi = {10.36740/WLek202210131}, pmid = {36472284}, issn = {0043-5147}, mesh = {Humans ; Young Adult ; Adult ; Blood Pressure Monitoring, Ambulatory ; Blood Pressure/physiology ; *COVID-19 ; *Hypertension ; Circadian Rhythm ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The aim: To perform an overall assessment of BP and BP variability using ambulatory measurements in young adults with long COVID syndrome.

PATIENTS AND METHODS: Materials and methods: We enrolled young patients with diagnosed long-COVID syndrome (n = 58, mean age 23.07 ± 1.54 years), compared with an age-matched healthy subjects who had not suffered from COVID-19 (n = 57, mean age 22.9 ± 1.83 years). Patients with long-COVID syndrome had recovered from mild/moderate illness and none had required hospitalization. Ambulatory 24 hours blood pressure (AMBP) parameters (mean BP, daytime BP, nighttime BP, pulse pressure, nocturnal systolic BP dipping, dipper status) were measured in all participants. The variability of systolic BP (SBP) and diastolic BP (DBP) values was assessed by the following common metrics, including the average real variability (ARV), the coefficient of variation (CV), the standard deviation (SD), and the weighed SD of SBP and DBP.

RESULTS: Results: The average values of 24-hour ambulatory blood pressure, mean BP, daytime and nighttime systolic BP, diastolic BP and pulse pressure were found to be significantly different among patients with long COVID syndrome and control group. Group analyses showed that this difference was in SBP mean values (127.1 ± 6.65 mmHg and 115.93 ± 6.24 mmHg respectively) and DBP mean values (73.31 ± 5.30 mmHg and 68.79 ± 5.5 mmHg respectively) mainly at night. PP values at daytime were almost similar among groups, but PP values at nighttime were higher in patients with long-COVID syndrome (53.8 (52.44- 55.14) mmHg and 47.14 (46.45 - 47.88) mmHg respectively). Nocturnal SBP dipping was better in control group than in patients with long-COVID syndrome (5.3 ± 5.68 and 3.1 ± 3.79 mmHg respectively). Only 13 (22.4%) patients with long-COVID syndrome had normal dip-per status while more than half - 38 (66.7%) in healthy subjects. The values of ARV of SBP and DBP over 24-hour, awake, and asleep time frames were found to be greater in patients with long COVID syndrome than healthy controls (p < 0.05).

CONCLUSION: Conclusions: Patients with long- COVID syndrome have higher BP mean values of 24-hour ABPM particularly at nightime, significant blood pressure BP variability, which increases the risk of cardiovascular events in future. Nevertheless, the further prospective investigations is warranted to investigate the potential mechanisms and causality associations.}, } @article {pmid36471749, year = {2023}, author = {Leaman, R and Islamaj, R and Allot, A and Chen, Q and Wilbur, WJ and Lu, Z}, title = {Comprehensively identifying Long Covid articles with human-in-the-loop machine learning.}, journal = {Patterns (New York, N.Y.)}, volume = {4}, number = {1}, pages = {100659}, pmid = {36471749}, issn = {2666-3899}, abstract = {A significant percentage of COVID-19 survivors experience ongoing multisystemic symptoms that often affect daily living, a condition known as Long Covid or post-acute-sequelae of SARS-CoV-2 infection. However, identifying scientific articles relevant to Long Covid is challenging since there is no standardized or consensus terminology. We developed an iterative human-in-the-loop machine learning framework combining data programming with active learning into a robust ensemble model, demonstrating higher specificity and considerably higher sensitivity than other methods. Analysis of the Long Covid Collection shows that (1) most Long Covid articles do not refer to Long Covid by any name, (2) when the condition is named, the name used most frequently in the literature is Long Covid, and (3) Long Covid is associated with disorders in a wide variety of body systems. The Long Covid Collection is updated weekly and is searchable online at the LitCovid portal: https://www.ncbi.nlm.nih.gov/research/coronavirus/docsum?filters=e_condition.LongCovid.}, } @article {pmid36471421, year = {2023}, author = {Taghadosi, M and Safarzadeh, E and Asgarzadeh, A and Roghani, SA and Shamsi, A and Jalili, C and Assar, S and Soufivand, P and Pournazari, M and Feizollahi, P and Nicknam, MH and Asghariazar, V and Vaziri, S and Shahriari, H and Mohammadi, A}, title = {Partners in crime: Autoantibodies complicit in COVID-19 pathogenesis.}, journal = {Reviews in medical virology}, volume = {33}, number = {2}, pages = {e2412}, pmid = {36471421}, issn = {1099-1654}, mesh = {Crime ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Humans ; Autoantibodies ; }, abstract = {Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.}, } @article {pmid36470824, year = {2022}, author = {Dove, S and Turlington, L and Elmendorf, K and Mahachi, K and Petersen, C and Meyer, D}, title = {Singing Voice Symptomatology Following Presumed SARS-CoV-2 Infection.}, journal = {Journal of voice : official journal of the Voice Foundation}, volume = {}, number = {}, pages = {}, pmid = {36470824}, issn = {1873-4588}, abstract = {The impact of continued COVID-19 sequelae on singers' vocal function has yet to be determined. An online survey of singers who have contracted SARS-CoV-2 infection was designed and administered globally. Participants (n = 1,153) were recruited in Africa, the Americas, Asia, Australia, and Europe. Survey questions included demographics, peri- and post-SARS-CoV-2 infection symptoms, and self-reported sequelae attributed to long-COVID. The survey was made available in English, Portuguese, Spanish, and Traditional and Simplified Mandarin Chinese. Data were statistically analyzed to provide a useful summary of the sample and to evaluate associations between long-COVID and singers' vocal function. We found that age, gender, and vaccination status were not significantly correlated to a change in singing voice in our sample. However, severity of infection was statistically correlated with a change in singing voice. Of the 34 signs and symptoms presented, lingering cough, shortness of breath, and chronic fatigue were significantly correlated with a change in singing voice. These data and their analyses have added to our understanding of this growing population's unique vocal needs, and may inform strategies for singing voice habilitation in COVID-19 survivors.}, } @article {pmid36470237, year = {2023}, author = {Hatabu, H and Kaye, KM and Christiani, DC}, title = {Viral Infection, Pulmonary Fibrosis, and Long COVID.}, journal = {American journal of respiratory and critical care medicine}, volume = {207}, number = {6}, pages = {647-649}, pmid = {36470237}, issn = {1535-4970}, support = {R01 AI150575/AI/NIAID NIH HHS/United States ; R01 AI165382/AI/NIAID NIH HHS/United States ; R01 DE025208/DE/NIDCR NIH HHS/United States ; R01CA203636/NH/NIH HHS/United States ; 5U01CA209414/NH/NIH HHS/United States ; R01HL111024/NH/NIH HHS/United States ; R01HL135142/NH/NIH HHS/United States ; R01HL130974/NH/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; *Pulmonary Fibrosis/etiology ; Post-Acute COVID-19 Syndrome ; *Virus Diseases ; Hospitalization ; Lung ; }, } @article {pmid36468825, year = {2022}, author = {Negrini, S and Kiekens, C and Cordani, C and Arienti, C and DE Groote, W}, title = {Cochrane "evidence relevant to" rehabilitation of people with post COVID-19 condition. What it is and how it has been mapped to inform the development of the World Health Organization recommendations.}, journal = {European journal of physical and rehabilitation medicine}, volume = {58}, number = {6}, pages = {853-856}, pmid = {36468825}, issn = {1973-9095}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *COVID-19/epidemiology ; Evidence-Based Medicine ; *Pandemics ; Post-Acute COVID-19 Syndrome ; Systematic Reviews as Topic ; }, abstract = {Cochrane Rehabilitation developed a series of actions to provide the global rehabilitation community with the best available evidence to respond to the COVID-19 pandemic. These initiatives constituted the REH-COVER (Rehabilitation COVID-19 evidence-based response) action. In March 2020, the first initiative started in agreement with the European Journal of Physical and Rehabilitation Medicine (EJPRM): the rapid systematic review of all papers relevant to COVID-19 rehabilitation to inform rehabilitation health professionals rapidly. Currently, we are facing the long-term consequences of COVID-19, initially called "long Covid" and now named post COVID-19 condition (PCC), which led to the request by the WHO Rehabilitation Programme for evidence synthesis to support the development of specific recommendations. Cochrane Rehabilitation provided the best available evidence from the REH-COVER rapid living systematic review results, a systematic scoping review on the models of care and a summary of "evidence relevant to" the rehabilitation for adults with PCC. Based on this evidence, expert groups developed the 16 recommendations for the rehabilitation of adults with PCC recently published in Chapter 24 of the WHO "Clinical management of COVID-19 living guideline." This paper aims to introduce the Special Section of EJPRM reporting the work performed by Cochrane Rehabilitation to produce a summary of the existing "evidence relevant to" the rehabilitation of adults with PCC. The paper reports the methodology (overview of systematic reviews with mapping) and introduces the concept of "evidence relevant to" rehabilitation.}, } @article {pmid36468196, year = {2023}, author = {Baimukhamedov, C}, title = {How long is long COVID.}, journal = {International journal of rheumatic diseases}, volume = {26}, number = {2}, pages = {190-192}, pmid = {36468196}, issn = {1756-185X}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Arthritis, Rheumatoid ; }, } @article {pmid36466841, year = {2022}, author = {Jing, H and Wu, X and Xiang, M and Liu, L and Novakovic, VA and Shi, J}, title = {Pathophysiological mechanisms of thrombosis in acute and long COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {992384}, pmid = {36466841}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis/etiology ; Anticoagulants/therapeutic use ; Phosphatidylserines ; Cytokine Release Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe COVID-19 and high mortality. COVID-19 disease is associated with a hyper-inflammatory response (cytokine storm) mediated by the immune system. However, the role of the inflammatory response in thrombosis remains incompletely understood. In this review, we investigate the crosstalk between inflammation and thrombosis in the context of COVID-19, focusing on the contributions of inflammation to the pathogenesis of thrombosis, and propose combined use of anti-inflammatory and anticoagulant therapeutics. Under inflammatory conditions, the interactions between neutrophils and platelets, platelet activation, monocyte tissue factor expression, microparticle release, and phosphatidylserine (PS) externalization as well as complement activation are collectively involved in immune-thrombosis. Inflammation results in the activation and apoptosis of blood cells, leading to microparticle release and PS externalization on blood cells and microparticles, which significantly enhances the catalytic efficiency of the tenase and prothrombinase complexes, and promotes thrombin-mediated fibrin generation and local blood clot formation. Given the risk of thrombosis in the COVID-19, the importance of antithrombotic therapies has been generally recognized, but certain deficiencies and treatment gaps in remain. Antiplatelet drugs are not in combination with anticoagulant treatments, thus fail to dampen platelet procoagulant activity. Current treatments also do not propose an optimal time for anticoagulation. The efficacy of anticoagulant treatments depends on the time of therapy initiation. The best time for antithrombotic therapy is as early as possible after diagnosis, ideally in the early stage of the disease. We also elaborate on the possible mechanisms of long COVID thromboembolic complications, including persistent inflammation, endothelial injury and dysfunction, and coagulation abnormalities. The above-mentioned contents provide therapeutic strategies for COVID-19 patients and further improve patient outcomes.}, } @article {pmid36466420, year = {2022}, author = {Conte, C and Muscaritoli, M}, title = {Editorial: Muscle mass and function in COVID-19.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1012742}, pmid = {36466420}, issn = {2296-861X}, } @article {pmid36466122, year = {2023}, author = {Nouraeinejad, A}, title = {Brain fog as a Long-term Sequela of COVID-19.}, journal = {SN comprehensive clinical medicine}, volume = {5}, number = {1}, pages = {9}, pmid = {36466122}, issn = {2523-8973}, abstract = {Increasing data indicate that people infected with COVID-19 are at high risk for developing long-term neurological complications, such as "brain fog" or cognitive impairment. However, little is known about the long-term outcomes of COVID-19 survivors. This also applies to the prevalence, risk factors, and pathobiological findings associated with these consequences. Although cognitive complications are anticipated in patients who require a long-lasting hospital stay or intubation, milder cases of COVID-19 with no record of hospitalization have also been shown to experience assessable cognitive challenges. Cognitive impairment can have a devastating impact on daily functioning. Understanding the long-term effect of COVID-19 on cognitive function is vital for applying specific schemes to those who wish to return to their jobs productively.}, } @article {pmid36466050, year = {2022}, author = {Ghasemi, D and Araeynejad, F and Maghsoud, O and Gerami, N and Keihan, AH and Rezaie, E and Mehdizadeh, S and Hosseinzadeh, R and Mohammadi, R and Bahardoust, M and Heiat, M}, title = {The Trend of IgG and IgM Antibodies During 6-Month Period After the Disease Episode in COVID-19 Patients.}, journal = {Iranian journal of science and technology. Transaction A, Science}, volume = {46}, number = {6}, pages = {1555-1562}, pmid = {36466050}, issn = {1028-6276}, abstract = {UNLABELLED: SARS-CoV-2 is a newly emerged coronavirus that has been widely transmitted since late 2019. It has caused a pandemic and infected roughly 450 million people globally.Hitherto, there is no approved anti-COVID-19 treatment, and vaccination is the only experienced preventive strategy. It mainly promotes the immune system, which is vital as a barrier against COVID-19. Humoral immunity (antibody-mediated immunity), among the various functions of the immune system against the coronavirus, plays an outstanding role in preventing infection. Consequently, we intended to assess IgG and IgM antibodies, 3 and 6 months after infection, to trend their titer and see how long COVID-19 antibodies remained in the human body. According to the research-designed criteria, only 98 patients out of 4500 suspected cases of SARS-CoV-2 infection remained for analysis. Blood samples were taken in three time periods (Day Zero (T 0), 3 and 6 months post-infection) and examined for COVID-19's IgG and IgM antibodies titration using the ELISA platform. Though both IgG and IgM were still detectable for some subjects at the end of the period, the decline in their levels (from 14.45 ± 5.88 to 2.52 ± 2.33 for IgG [85% decline of antibody titer] and 8.3 ± 0.99 to 0.37 ± 0.14 for IgM [95.5% decline of antibody titer]) was statistically significant (P value 0.0001). There was no correlation between gender and IgG and IgM levels. Although the levels of both antibodies were overall higher in the senior group (≥ 60 years old), statistical analysis showed a significantly higher level just for IgM in this group (P value: 0.005). Following the results, although anti-SARS-CoV-2 IgM and IgG antibodies can persist in the blood for 6 months post-infection, their levels steeply declined over time. Therefore, relying on humoral immunity as a trustworthy barrier against SARS-CoV-2 infection calls for more extensive research.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40995-022-01382-7.}, } @article {pmid36465224, year = {2022}, author = {Hariri, N and Takrooni, W and Nasraldin, N and Bawahab, N and Alfalogy, E}, title = {Effect of the Long COVID-19 Quarantine and Associated Lack of Physical Activity on Overall Health.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e30955}, pmid = {36465224}, issn = {2168-8184}, abstract = {Background The COVID-19 pandemic's mandatory quarantine encouraged a sedentary lifestyle, which had detrimental effects on health. The purpose of this study is to evaluate the health effects of the prolonged COVID-19 quarantine. Methods A descriptive cross-sectional study was conducted using an online questionnaire to assess the effects of physical activity and dietary patterns on weight gain and perceived stress. Results Of the 384 participants, the majority (58.6%) experienced stress, while 22.4% saw a dramatic decline in physical activity and only 19.8% performed regular physical activity. Although 64.1% of the participants reported eating healthily, 40.6% gained weight during the quarantine. Insufficient exercise (OR 1.966, 95% CI: 1.001-3.858) and consuming soft drinks frequently (OR 2.363, 95% CI: 1.137-4.910) were the two most important predictors of weight gain. The likelihood of developing psychological stress was increased by consuming more food (OR 2.592, 95% CI; 1.268-5.298), eating few vegetables (OR 3.154, 95% CI: 1.203-8.269), and insufficient exercising (OR 2.211, 95% CI: 1.063-4.600). Conclusion Long quarantines and physical inactivity raise the risk of weight gain and stress, both of which have detrimental effects on general health.}, } @article {pmid36465192, year = {2022}, author = {Chatterjee, E and Khan, T and Renzi, LS and Charles, EJ and Mandalaneni, K}, title = {A Bibliometric Analysis of COVID-19 Scientific Literature From the English-Speaking Caribbean.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e30958}, pmid = {36465192}, issn = {2168-8184}, abstract = {The COVID-19 pandemic has led to a global crisis and has affected the Caribbean islands, leading to significant health and socioeconomic consequences in this region. Efforts to mitigate the burden of this disease have led to an accelerated amount of research in the English-speaking Caribbean (ESC). This bibliometric analysis aimed to evaluate the COVID-19-related scientific literature from the ESC nations. A total of 175 articles were included and analyzed from an initial PubMed search (n = 638) for COVID-19-related scientific literature from the ESC nations published between January 1, 2020, and June 30, 2022. Microsoft Excel 2016 (Microsoft Corporation, Redmond, Washington) and the VOSviewer (version 1.6.18) were used to characterize countries, authorship, journals, affiliations, and keywords of the COVID-19-related articles. Trinidad and Tobago (38%), Jamaica (22%), Barbados (20%), and Grenada (15%) contributed to the greatest number of publications. The University of the West Indies (UWI) campuses in Trinidad and Tobago, Jamaica and Barbados, and St. George's University in Grenada were the most prolific institutions. Srikanth Umakanthan from the UWI was the most prolific author. Cureus, SN Comprehensive Clinical Medicine, and Frontiers in Public Health were the first three most productive journals; 59% of the 175 articles had either the first or last author affiliated with an institution in the ESC, and 19% of the articles were country-focused: Trinidad and Tobago (16/175), Jamaica (9/175), Barbados (5/175), and Antigua and Barbuda (2/175). Among the top themes of research, 27% were outbreak response and rearrangements, epidemiological studies (23%), clinical management (23%), and medical education (13%). Over the last two years, an interest stimulated by the pandemic has expanded the research in ESC countries. However, gaps in the knowledge exist, especially in the epidemiology of COVID-19 complications in the sub-populations of chronic non-communicable diseases, post-COVID syndrome, and the long-COVID syndrome in the region. Hence, there is enormous scope for more research across the region.}, } @article {pmid36464877, year = {2023}, author = {Scarpellini, E and Tack, J}, title = {Post-COVID-19 Gastro-Intestinal Disturbances.}, journal = {Reviews on recent clinical trials}, volume = {18}, number = {1}, pages = {34-40}, doi = {10.2174/1574887118666221201104833}, pmid = {36464877}, issn = {1876-1038}, mesh = {Humans ; *Irritable Bowel Syndrome/complications/diagnosis/therapy ; *COVID-19/complications ; SARS-CoV-2 ; *Gastrointestinal Diseases/etiology/diagnosis ; *Dyspepsia ; }, abstract = {BACKGROUND: Since the end of 2019, SARS-CoV-2 has been responsible for the multisystemic hyper-inflammatory disease, namely, COVID-19, as a majorly impactful pandemic. Gastrointestinal (GI) symptoms occurring during and after disease are gaining increasing attention among experts.

METHODS: We briefly review and comment on preliminary and recent evidences on prevalence, pathophysiology, and perspective treatment options for GI disturbances during and after COVID-19.

RESULTS: Several reports from the literature show a significant portion of COVID-19 patients suffering from GI symptoms both at the early stages of the disease and after the end of it, sometimes for several months, namely "long-COVID-19" patients, irrespective of vaccination. An unsolved issue regarding COVID-19 is the association between GI symptoms and the outcome of COVID-19 patients. Several studies and metanalyses suggest a worse evolution of COVID-19 in patients presenting with GI symptoms. However, these data have not been agreed. Indeed, only one uniform observation can be found in the literature: patients with chronic liver disease have a worse outcome from COVID-19 infection. Upper and lower GI symptoms have similarities with postinfectious functional dyspepsia (FD) and irritable bowel syndrome (IBS). FD and IBS following infection are recognize as pathophysiological factor the gut microbial, which is a gut microbial quali- and quantitative unbalance, namely dysbiosis. Furthermore, several preliminary reports and ongoing clinical trials have shown gut microbiota modulation by pre-, pro- and postbiotics to be effective in changing and preventing COVID-19 natural course.

CONCLUSION: GI symptoms characterize both long- and non-long-COVID-19 with a potentially significant impact on its natural course. Gut microbiota modulation seems to be a sensible target for disease treatment and/or prevention.}, } @article {pmid36462554, year = {2023}, author = {Faghy, MA and Ashton, REM and Parizher, G and Smith, A and Arena, R and Gough, LA and Emery, MS}, title = {COVID-19 and elite sport: Cardiovascular implications and return-to-play.}, journal = {Progress in cardiovascular diseases}, volume = {76}, number = {}, pages = {61-68}, pmid = {36462554}, issn = {1873-1740}, mesh = {Humans ; *COVID-19/epidemiology ; Return to Sport ; Post-Acute COVID-19 Syndrome ; *Sports ; Athletes ; }, abstract = {Curtailing elite sports during the coronavirus disease 2019 (COVID-19) pandemic was necessary to prevent widespread viral transmission. Now that elite sport and international competitions have been largely restored, there is still a need to devise appropriate screening and management pathways for athletes with a history of, or current, COVID-19 infection. These approaches should support the decision-making process of coaches, sports medicine practitioners and the athlete about the suitability to return to training and competition activities. In the absence of longitudinal data sets from athlete populations, the incidence of developing prolonged and debilitating symptoms (i.e., Long COVID) that affects a return to training and competition remains a challenge to sports and exercise scientists, sports medicine practitioners and clinical groups. As the world attempts to adjust toward 'living with COVID-19' the very nature of elite and international sporting competition poses a risk to athlete welfare that must be screened for and managed with bespoke protocols that consider the cardiovascular implications for performance.}, } @article {pmid36462223, year = {2023}, author = {Gemignani, F and Bellanova, MF and Saccani, E}, title = {Long-COVID phenotypes and small fiber neuropathy.}, journal = {Journal of the neurological sciences}, volume = {444}, number = {}, pages = {120490}, doi = {10.1016/j.jns.2022.120490}, pmid = {36462223}, issn = {1878-5883}, mesh = {Humans ; *Small Fiber Neuropathy/complications/diagnosis/genetics ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Autonomic Nervous System Diseases ; Phenotype ; }, } @article {pmid36462147, year = {2023}, author = {Karavanaki, K and Rodolaki, K and Soldatou, A and Karanasios, S and Kakleas, K}, title = {Covid-19 infection in children and adolescents and its association with type 1 diabetes mellitus (T1d) presentation and management.}, journal = {Endocrine}, volume = {80}, number = {2}, pages = {237-252}, pmid = {36462147}, issn = {1559-0100}, mesh = {Adult ; *COVID-19/complications ; Pandemics ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; Adolescent ; SARS-CoV-2 ; *Diabetes Mellitus, Type 1/complications/therapy ; Systemic Inflammatory Response Syndrome ; *Diabetes Mellitus, Type 2/complications/epidemiology ; }, abstract = {Children seem to be affected by the new SARS-CoV-2 virus less severely than adults, with better prognosis and low mortality. Serious complications of COVID-19 infection in children include multisystem inflammatory response syndrome in COVID-19 infection (MIS-C), myo-or pericarditis and, less frequently, long COVID syndrome. On the other hand, adults with type 1 (T1D) or type 2 diabetes (T2D) are among the most vulnerable groups affected by COVID-19, with increased morbidity and mortality. Moreover, an association of SARS-CoV-2 with diabetes has been observed, possibly affecting the frequency and severity of the first clinical presentation of T1D or T2D, as well as the development of acute diabetes after COVID-19 infection. The present review summarizes the current data on the incidence of T1D among children and adolescents during the COVID-19 pandemic, as well as its severity. Moreover, it reports on the types of newly diagnosed diabetes after COVID infection and the possible pathogenetic mechanisms. Additionally, this study presents current data on the effect of SARS-CoV-2 on diabetes control in patients with known T1D and on the severity of clinical presentation of COVID infection in these patients. Finally, this review discusses the necessity of immunization against COVID 19 in children and adolescents with T1D.}, } @article {pmid36461167, year = {2023}, author = {Parker, M and Sawant, HB and Flannery, T and Tarrant, R and Shardha, J and Bannister, R and Ross, D and Halpin, S and Greenwood, DC and Sivan, M}, title = {Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28373}, pmid = {36461167}, issn = {1096-9071}, mesh = {Humans ; *COVID-19/therapy ; Quality of Life ; Post-Acute COVID-19 Syndrome ; *Fatigue Syndrome, Chronic ; Prospective Studies ; Symptom Flare Up ; Health Status ; }, abstract = {Post-exertional symptom exacerbation (PESE) is a characteristic symptom of post-COVID syndrome (PCS). This prospective study investigated the effect of a 6-week structured World Health Organization (WHO) Borg CR-10 5-phase pacing protocol on PESE episodes and quality of life in a cohort of individuals with long-standing PCS (average duration of symptoms was 17 months). Participants received weekly telephone calls with a clinician to complete the Leeds PESE questionnaire (LPQ) and identify the appropriate phase of the pacing protocol. EQ-5D 5L was completed at the intervention's beginning and end to measure overall health. Thirty-one participants completed the 6-week protocol, with a statistically and clinically significant reduction in the average number of PESE episodes (from 3.4 episodes in Week 1 to 1.1 in Week 6), with an average decrease of 16% (95% CI: 9%-24%; p < 0.001) each week, and reduction across all three exertional triggers (physical, cognitive, and emotional). Physical activity levels showed moderate improvements during the intervention period. Mean EQ-5D 5L scores improved from 51.4 to 60.6 points (paired difference of 9.2 points, 95% CI: 3.2-15.2 points; p = 0.004). A structured pacing protocol significantly reduces PESE episodes and improves overall health in PCS.}, } @article {pmid36460367, year = {2022}, author = {Vishnu Sharma, M and Arora, VK and Anupama, N}, title = {Role of chest radiography in the diagnosis of pulmonary tuberculosis during nCovid19 pandemic.}, journal = {The Indian journal of tuberculosis}, volume = {69}, number = {4}, pages = {385-388}, doi = {10.1016/j.ijtb.2022.03.008}, pmid = {36460367}, issn = {0019-5707}, mesh = {Humans ; Pandemics ; *COVID-19/diagnosis ; *Bronchopneumonia ; *Tuberculosis, Pulmonary/diagnostic imaging/epidemiology ; Radiography ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pulmonary tuberculosis and nCovid 19 share many common risk factors. nCovid19 may increase the risk to develop pulmonary tuberculosis. Pulmonary tuberculosis may precede, co-exist or follow nCovid19. Careful evaluation of chest radiography is useful to differentiate tuberculosis from nCovid19 bronchopneumonia. Symptoms of tuberculosis may be mistaken for long covid. A normal chest x ray in the absence of sputum production may help to rule out tuberculosis in such cases. All patients with nCovid19 bronchopneumonia should undergo a careful chest x ray evaluation for any lesions suggestive of tuberculosis. All patients with chest radiological abnormality should undergo sputum examination to rule tuberculosis as atypical radiological manifestations may be more common in patients with nCovid19. Symptoms, signs, clinical features and chest radiographic features of Pulmonary tuberculosis and nCovid19 bronchopneumonia may overlap in some cases. Correlation of chest radiographic findings with epidemiologic history, clinical presentation, and RT-PCR test results or in later stages antibody titres will help in confirming or excluding the diagnosis in suspected cases of nCovid19. In pulmonary tuberculosis definitive diagnosis should be established by bacteriological confirmation. Molecular diagnostic tools should be used to confirm or exclude tuberculosis in suspect cases as the results are rapid, accurate and reliable.}, } @article {pmid36458712, year = {2022}, author = {Tahmaz, A and Çetin, E and Balcı, U and Sarıgül Yıldırım, F and Seyman, D and Gürgen, A}, title = {[The Evaluation of Long Coronavirus Disease Symptoms at Ninth Month from a Hospital in Türkiye].}, journal = {Mikrobiyoloji bulteni}, volume = {56}, number = {4}, pages = {657-666}, doi = {10.5578/mb.20229604}, pmid = {36458712}, issn = {0374-9096}, mesh = {Humans ; Female ; Male ; Adult ; Middle Aged ; *Coronavirus ; *COVID-19 ; Cross-Sectional Studies ; *Coronavirus Infections ; Hospitals ; Alopecia ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is defined as symptoms related to various organs following COVID-19. There is currently very little information available about the prevalence of these symptoms and their long-term recovery time. The aim of this study was to describe the symptoms that persisted nine months after COVID-19. This cross-sectional study was conducted in Antalya, Türkiye, between November 1 and 30, 2020 on COVID-19 patients. Patients were contacted approximately nine months later by two infectious diseases physicians, and the questionnaire which included 27 symptoms was completed. Of the 390 patients who met the criteria, 329 agreed to participate in the study. Patients' average age was 48.9 ± 14.4 years, and 51.7% were male. 79.3% of the people still had at least one symptom at the end of the ninth month. The most common symptoms were weakness-fatigue (54.7%), forgetfulness (45.3%), effort loss (35.0%), sleep disturbance (34.3%), joint pain (27.4%), and hair loss (23.4%). According to analysis performed in terms of sex; hair loss, diarrhea, nausea, dizziness, sore throat, loss of taste and smell were more common in women than in men (p= 0.042, p= 0.047, p= 0.050, p= 0.026, p= 0.016, p= 0.036, p= 0.027, respectively). Individuals aged 65 years and over had a significantly lower number of symptoms (p= 0.029) than all other age groups. Furthermore, the number of symptoms was higher in patients who used steroids (p= 0.049). This study is an important source of information on the long-term symptoms of COVID-19. Our results have shown that the symptoms associated with COVID-19 do not completely resolve even after nine months, which explains why long COVID requires continuous monitoring.}, } @article {pmid36458566, year = {2023}, author = {Schultheiß, C and Willscher, E and Paschold, L and Gottschick, C and Klee, B and Bosurgi, L and Dutzmann, J and Sedding, D and Frese, T and Girndt, M and Höll, JI and Gekle, M and Mikolajczyk, R and Binder, M}, title = {Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28364}, pmid = {36458566}, issn = {1096-9071}, mesh = {Humans ; Biomarkers ; Cohort Studies ; COVID-19/complications ; Disease Progression ; *Post-Acute COVID-19 Syndrome/diagnosis/metabolism ; Quality of Life ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus/blood/chemistry ; Macrophages/metabolism ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that can substantially impair the quality of life. Underlying mechanisms ranging from persistent viruses to innate and adaptive immune dysregulation have been discussed. Here, we profiled the plasma of 181 individuals from the cohort study for digital health research in Germany (DigiHero), including individuals after mild to moderate COVID-19 with or without PASC and uninfected controls. We focused on soluble factors related to monocyte/macrophage biology and on circulating SARS-CoV-2 spike (S1) protein as a potential biomarker for persistent viral reservoirs. At a median time of 8 months after infection, we found pronounced dysregulation in almost all tested soluble factors, including both pro-inflammatory and pro-fibrotic cytokines. These immunological perturbations were remarkably independent of ongoing PASC symptoms per se, but further correlation and regression analyses suggested PASC-specific patterns involving CCL2/MCP-1 and IL-8 that either correlated with sCD162, sCD206/MMR, IFN-α2, IL-17A and IL-33, or IL-18 and IL-23. None of the analyzed factors correlated with the detectability or levels of circulating S1, indicating that this represents an independent subset of patients with PASC. These data confirm prior evidence of immune dysregulation and persistence of viral protein in PASC and illustrate its biological heterogeneity that still awaits correlation with clinically defined PASC subtypes.}, } @article {pmid36458509, year = {2023}, author = {Fancourt, D and Steptoe, A and Bu, F}, title = {Psychological consequences of long COVID: comparing trajectories of depressive and anxiety symptoms before and after contracting SARS-CoV-2 between matched long- and short-COVID groups.}, journal = {The British journal of psychiatry : the journal of mental science}, volume = {222}, number = {2}, pages = {74-81}, pmid = {36458509}, issn = {1472-1465}, support = {/WT_/Wellcome Trust/United Kingdom ; 205407/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 221400/WT_/Wellcome Trust/United Kingdom ; 221400/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Depression/epidemiology ; Anxiety/epidemiology/psychology ; }, abstract = {BACKGROUND: There is a growing global awareness of the psychological consequences of long COVID, supported by emerging empirical evidence. However, the emergence and long-term trajectories of psychological symptoms following the infection are still unclear.

AIMS: To examine when psychological symptoms first emerge following infection with SARS-CoV-2 and the long-term trajectories of psychological symptoms comparing long- and short-COVID groups.

METHOD: We analysed longitudinal data from the UCL COVID-19 Social Study (March 2020 to November 2021). We included data from adults living in England who reported contracting SARS-CoV-2 by November 2021 (n = 3115). Of these, 15.9% reported having had long COVID (n = 495). They were matched to participants who had short COVID using propensity score matching on a variety of demographic, socioeconomic and health covariates (n = 962 individuals with 13 325 observations) and data were further analysed using growth curve modelling.

RESULTS: Depressive and anxiety symptoms increased immediately following the onset of infection in both long- and short-COVID groups. But the long-COVID group had substantially greater initial increases in depressive symptoms and heightened levels over 22 months follow-up. Initial increases in anxiety were not significantly different between groups, but only the short-COVID group experienced an improvement in anxiety over follow-up, leading to widening differences between groups.

CONCLUSIONS: The findings support work on the psychobiological pathways involved in the development of psychological symptoms relating to long COVID. The results highlight the need for monitoring of mental health and provision of adequate support to be interwoven with diagnosis and treatment of the physical consequences of long COVID.}, } @article {pmid36457320, year = {2022}, author = {Bowie, C and Friston, K}, title = {A 12-month projection to September 2022 of the COVID-19 epidemic in the UK using a dynamic causal model.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {999210}, pmid = {36457320}, issn = {2296-2565}, mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Predicting the future UK COVID-19 epidemic allows other countries to compare their epidemic with one unfolding without public health measures except a vaccine program.

METHODS: A Dynamic Causal Model was used to estimate key model parameters of the UK epidemic, such as vaccine effectiveness and increased transmissibility of Alpha and Delta variants, the effectiveness of the vaccine program roll-out and changes in contact rates. The model predicts the future trends in infections, long-COVID, hospital admissions and deaths.

RESULTS: Two-dose vaccination given to 66% of the UK population prevents transmission following infection by 44%, serious illness by 86% and death by 93%. Despite this, with no other public health measures used, cases will increase from 37 million to 61 million, hospital admissions from 536,000 to 684,000 and deaths from 136,000 to 142,000 over 12 months. A retrospective analysis (conducted after the original submission of this report) allowed a comparison of these predictions of morbidity and mortality with actual outcomes.

CONCLUSION: Vaccination alone will not control the epidemic. Relaxation of mitigating public health measures carries several risks, which include overwhelming the health services, the creation of vaccine resistant variants and the economic cost of huge numbers of acute and chronic cases.}, } @article {pmid36457246, year = {2023}, author = {Chrapkowska, C}, title = {Mental and physical health should be evaluated in children and adolescents with long COVID.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {2}, pages = {176-177}, pmid = {36457246}, issn = {1651-2227}, mesh = {Adolescent ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; }, } @article {pmid36455453, year = {2023}, author = {Versace, V and Ortelli, P and Dezi, S and Ferrazzoli, D and Alibardi, A and Bonini, I and Engl, M and Maestri, R and Assogna, M and Ajello, V and Pucks-Faes, E and Saltuari, L and Sebastianelli, L and Kofler, M and Koch, G}, title = {Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {145}, number = {}, pages = {81-88}, pmid = {36455453}, issn = {1872-8952}, mesh = {Female ; Humans ; Adult ; Middle Aged ; *Luteolin/pharmacology ; Neural Inhibition/physiology ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Transcranial Magnetic Stimulation/methods ; gamma-Aminobutyric Acid ; Fatigue ; Evoked Potentials, Motor/physiology ; }, abstract = {OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI.

METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity.

RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected.

CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients.

SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.}, } @article {pmid36454631, year = {2023}, author = {Peluso, MJ and Deveau, TM and Munter, SE and Ryder, D and Buck, A and Beck-Engeser, G and Chan, F and Lu, S and Goldberg, SA and Hoh, R and Tai, V and Torres, L and Iyer, NS and Deswal, M and Ngo, LH and Buitrago, M and Rodriguez, A and Chen, JY and Yee, BC and Chenna, A and Winslow, JW and Petropoulos, CJ and Deitchman, AN and Hellmuth, J and Spinelli, MA and Durstenfeld, MS and Hsue, PY and Kelly, JD and Martin, JN and Deeks, SG and Hunt, PW and Henrich, TJ}, title = {Chronic viral coinfections differentially affect the likelihood of developing long COVID.}, journal = {The Journal of clinical investigation}, volume = {133}, number = {3}, pages = {}, pmid = {36454631}, issn = {1558-8238}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K24 AI145806/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K23 AG075262/AG/NIA NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; R01 HL152957/HL/NHLBI NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *HIV Infections/complications/epidemiology ; *Coinfection/epidemiology ; Fatigue/epidemiology/etiology ; *Cytomegalovirus Infections ; Immunoglobulin G ; Antibodies, Viral ; }, abstract = {BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).}, } @article {pmid36454120, year = {2023}, author = {Almulla, AF and Al-Hakeim, HK and Maes, M}, title = {Chronic fatigue and affective symptoms in acute and long COVID are attributable to immune-inflammatory pathways.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {2}, pages = {125-126}, pmid = {36454120}, issn = {1440-1819}, support = {64.310/169/2564//The study was funded by the C2F program, Chulalongkorn University, Thailand/ ; }, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis/metabolism ; Post-Acute COVID-19 Syndrome ; Affective Symptoms ; *COVID-19 ; Fatigue/etiology ; }, } @article {pmid36452019, year = {2022}, author = {Nguyen-Ho, L and Nguyen-Nhu, V and Tran-Thi, TT and Solomon, JJ}, title = {Severe chronic cough relating to post-COVID-19 interstitial lung disease: a case report.}, journal = {Asia Pacific allergy}, volume = {12}, number = {4}, pages = {e42}, pmid = {36452019}, issn = {2233-8276}, abstract = {Cough is a common symptom occurring in patients with acute coronavirus disease 2019 (COVID-19) infection as well as during the post-COVID-19 period. The post-COVID-19 cough can improve over time and the incidence of sustained post-COVID-19 chronic cough is low. Approaching post-COVID-19 cough is challenging to clinicians including pulmonologists and allergists due to a diverse set of etiologies and the lack of published guidance on effective treatments. A 60-year-old male ex-smoker presented to the outpatient long COVID-19 clinic because of a prolonged cough for 4 months after a severe COVID-19 infection. His cough was so violent that he had suffered a spontaneous pneumothorax on 2 occasions. In addition, he also complained of exertional breathlessness. Due to concerns over ongoing systemic inflammation from COVID-19 or thromboembolism, a serum C-reactive protein and d-dimer where checked and were normal. Chest computed tomography (CT) images revealed diffuse ground glass opacities combined with scattered emphysema in the bilateral upper lobes and several small bullae located close to the pleura. His diagnosis was post-COVID-19 interstitial lung disease (ILD) and he was treated with methylprednisolone 32 mg/day. After 2 weeks of treatment, he showed improvement with near cessation of cough and a significant decline in dyspnea. The follow-up chest CT also showed improvement in the ground glass opacities. Severe chronic cough could be a manifestation of post-COVID-19 ILD. This case demonstrates the use of systemic corticosteroid to improve both post-COVID-19 ILD and its associated chronic cough.}, } @article {pmid36451883, year = {2022}, author = {Rubinstein, R and Mei, W and Cassidy, CA and Streeter, G and Basham, C and Cerami, C and Lin, FC and Lin, JT and Mollan, KR}, title = {Transmission prevention behaviors in US households with SARS-CoV-2 cases in 2020.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36451883}, support = {P30 AI050410/AI/NIAID NIH HHS/United States ; T32 DK007634/DK/NIDDK NIH HHS/United States ; T32 GM008719/GM/NIGMS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: SARS-CoV-2 transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors.

METHODS: We analyzed a COVID-19 prospective household transmission cohort in North Carolina (April-Oct 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between Days 7-14.

RESULTS: In the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between Days 7-14 was reported by 26% of household contacts, and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case.

CONCLUSION: In-home masking during household exposure to COVID-19 was infrequent in 2020. In light of ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors.}, } @article {pmid36451331, year = {2022}, author = {Allard, N and Miller, A and Morgan, M and Chakraborty, S}, title = {Post-COVID-19 syndrome/condition or long COVID: Persistent illness after acute SARS CoV-2 infection.}, journal = {Australian journal of general practice}, volume = {51}, number = {12}, pages = {952-957}, doi = {10.31128/AJGP-05-22-6429}, pmid = {36451331}, issn = {2208-7958}, mesh = {Humans ; *COVID-19/complications ; Australia/epidemiology ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Approximately 10 million Australians have had confirmed SARS-CoV-2 infection. The waves of infection in the population have been succeeded by smaller waves of people affected by persistent illness following acute infection. Post-COVID-19 symptoms may extend for months following infection. There is a range of symptoms causing mild to debilitating impairment.

OBJECTIVE: This article summarises what is currently understood about the pathophysiology, risk factors, symptoms and how to approach both the assessment and care of people with post-COVID-19 sequelae.

DISCUSSION: Currently recommended is a person-centred approach from a multidisciplinary team, with general practitioners centrally coordinating care. As the understanding of post-acute COVID-19 is evolving, regularly updated or 'living guidelines' will be crucial for those affected to be provided with best care within the health system.}, } @article {pmid36450116, year = {2023}, author = {Spicuzza, L and Campisi, R and Alia, S and Prestifilippo, S and Giuffrida, ML and Angileri, L and Ciancio, N and Vancheri, C}, title = {Female Sex Affects Respiratory Function and Exercise Ability in Patients Recovered from COVID-19 Pneumonia.}, journal = {Journal of women's health (2002)}, volume = {32}, number = {1}, pages = {18-23}, doi = {10.1089/jwh.2022.0104}, pmid = {36450116}, issn = {1931-843X}, mesh = {Male ; Humans ; Female ; Acute Disease ; Retrospective Studies ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Exercise Tolerance ; }, abstract = {Background: Coronavirus-19 Disease (COVID-19) may cause persistent symptoms and functional respiratory impairment, known as long COVID. Determinants of long COVID are unclear. Although males experience more severe acute illness, the impact of sex on the occurrence of long-term sequelae is unknown. The aim of this study was to establish whether sex affects pulmonary function, exercise capacity, and clinical outcomes in patients recovered from COVID-19 pneumonia. Materials and Methods: We performed a retrospective analysis on patients evaluated in our "Post-COVID Clinic" after a median follow-up of 128 days from the acute disease. Tests performed included standard spirometry, diffusion capacity of the lung for carbon monoxide (DLCO), and 6-minute walk test (6-MWT). Results: A total of 157 patients (mean age 59.9 ± 12, 91 males) recovered from mild to severe pneumonia, without previous respiratory disease, were included. No differences in demographic data and in the severity of the acute illness were observed between the two study groups, males and females. Abnormal alveolar diffusion was more common and severe among females (DLCO <80% in 31% of males vs. 53% of females, p < 0.01; DLCO <70%, in 20% of males vs. 40% of females, p < 0.01). Severe reduction in 6-MWT was observed in 20% of males versus 46% of females (p < 0.01). Multiple logistic regression showed that female sex was an independent predictor of abnormal DLCO and 6-MWT. The prevalence of symptoms and radiological abnormalities was similar in the two groups. Conclusions: These data show that at 4 months follow-up women recovered from COVID-19 pneumonia are more likely to exhibit a reduced alveolar diffusion capacity and exercise tolerance than men, although a similar severity of the acute disease.}, } @article {pmid36449461, year = {2022}, author = {van der Feltz-Cornelis, CM and Sweetman, J and Allsopp, G and Attree, E and Crooks, MG and Cuthbertson, DJ and Forshaw, D and Gabbay, M and Green, A and Heightman, M and Hillman, T and Hishmeh, L and Khunti, K and Lip, GYH and Lorgelly, P and Montgomery, H and Strain, WD and Wall, E and Watkins, C and Williams, N and Wootton, DG and Banerjee, A and , }, title = {STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol.}, journal = {PloS one}, volume = {17}, number = {11}, pages = {e0277936}, pmid = {36449461}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology ; Critical Pathways ; Mental Health ; *Delivery of Health Care, Integrated ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: As mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs.

METHODS AND ANALYSIS: This study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID.

ETHICS AND DISSEMINATION: Ethical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID.

REGISTRATION: Researchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.}, } @article {pmid36449260, year = {2023}, author = {Di Gennaro, F and Belati, A and Tulone, O and Diella, L and Fiore Bavaro, D and Bonica, R and Genna, V and Smith, L and Trott, M and Bruyere, O and Mirarchi, L and Cusumano, C and Dominguez, LJ and Saracino, A and Veronese, N and Barbagallo, M}, title = {Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients.}, journal = {Internal and emergency medicine}, volume = {18}, number = {5}, pages = {1573-1581}, pmid = {36449260}, issn = {1970-9366}, support = {ffr//Università degli Studi di Palermo/ ; }, mesh = {Female ; Humans ; Middle Aged ; Male ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Incidence ; RNA, Viral ; }, abstract = {The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2-61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.}, } @article {pmid36448687, year = {2023}, author = {Ramírez-Vélez, R and Legarra-Gorgoñon, G and Oscoz-Ochandorena, S and García-Alonso, Y and García-Alonso, N and Oteiza, J and Ernaga Lorea, A and Correa-Rodríguez, M and Izquierdo, M}, title = {Reduced muscle strength in patients with long-COVID-19 syndrome is mediated by limb muscle mass.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {134}, number = {1}, pages = {50-58}, pmid = {36448687}, issn = {1522-1601}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; Aftercare ; *COVID-19 ; Patient Discharge ; Muscle Weakness ; Muscle Strength/physiology ; Body Composition/physiology ; Hand Strength/physiology ; Muscles ; Muscle, Skeletal/physiology ; Absorptiometry, Photon/methods ; }, abstract = {Understanding the impact of COVID-19 on muscle strength may help to elucidate the organ systems that contribute to acute and chronic COVID-19 sequelae. We questioned whether patients with postdischarge symptoms after COVID-19 had compromised muscle strength compared with a control group, and if this potential relationship was mediated by the lower appendicular lean mass index (ALMI). A total of 99 patients with long-COVID-19 and 97 control participants were screened. Maximal grip strength was assessed with a TKK 5101 digital dynamometer, and leg extension 1RM was measured using EGYM Smart Strength machines. Body composition (fat mass percentage, lean mass, visceral fat, and appendicular lean mass index) was determined using a whole body dual-energy X-ray densitometer. Results showed that grip strength and leg extension strength were significantly higher in controls than in COVID-19 survivors (mean [SD], 32.82 [10.01] vs. 26.94 [10.33] kg; difference, 5.87 kg; P < 0.001) and (mean [SD], 93.98 [33.73] vs. 71.59 [33.70] kg; difference, 22.38 kg; P < 0.001), respectively). The relationship between long-COVID syndrome and grip/leg strength levels was partly mediated by ALMI, which explained 52% of the association for grip strength and 39% for leg extension. Our findings provide novel insights into the mechanisms underlying the relationship between long-COVID syndrome and grip/leg strength levels, supporting the negative effects of long-COVID syndrome on muscle function.NEW & NOTEWORTHY The causes of post-COVID-19 syndrome are uncertain. Limb muscle wasting common to patients with COVID-19 limits daily activities and exercise. In this cross-sectional study, we found that patients with long-COVID-19 syndrome had significantly lower absolute and relative muscle strength measurements than control participants. Interestingly, we identified that these relationships were mostly mediated by limb muscle mass. Our data thus suggest that the evident reduced upper and lower muscle mass is a putative cause of-or contributor to-the functional limitation of patients with long-COVID-19 syndrome.}, } @article {pmid36447953, year = {2022}, author = {Ali, M}, title = {Severe acute respiratory syndrome coronavirus 2 infection altered the factors associated with headache: evidence from a multicenter community-based case-control study.}, journal = {Pain reports}, volume = {7}, number = {6}, pages = {e1051}, pmid = {36447953}, issn = {2471-2531}, abstract = {INTRODUCTION: Headache is one of the significant global public health concerns. Furthermore, it is a standard feature of patients with acute and postacute COVID-19.

OBJECTIVES: This study aimed to estimate and compare the prevalence of headaches among postacute COVID and non-COVID individuals and identify and contrast the risk factors between both groups.

METHODS: This was a multicenter case-control study. Individuals who had recovered from acute SARS-CoV-2 infection were considered "case", and those who never tested positive for COVID-19 were considered "control." Headaches were measured using the musculoskeletal subscale of the subjective health complaints scale. Multiple logistic regression analysis was used to identify the predictors of headaches.

RESULTS: A total of 878 individuals (439 cases) aged 38.30 ± 12.77 years (mean ± standard deviation) participated in this study. The prevalence of headaches was 26.2% among COVID-19 survivors; however, only 10.7% of unaffected participants reported headaches at the same time. Regression analyses suggested that the recovery duration from acute COVID-19 ≤ 90 days (adjusted odds ratio [AOR] = 2.03, CI = 1.13-3.65) was the only predictor of headache among postacute COVID-19 survivors. However, the female gender (AOR = 3.09, 95% CI = 1.51-6.32), members of a joint family (AOR = 1.99, 95% CI = 1.02-3.90), and city dwellers (AOR = 2.43, 95% CI = 0.94-6.25) were the predictor of headache among non-COVID participants.

CONCLUSION: This study found a higher prevalence of headaches among COVID-19 survivors. In addition, predictors of headache among cases and controls were unmatched, indicating heterogenous impact of COVID-19 on human health. The health care providers should be informed of the study's results when discussing better practices to mitigate the burden of headaches.}, } @article {pmid36447795, year = {2022}, author = {Déguilhem, A and Malaab, J and Talmatkadi, M and Renner, S and Foulquié, P and Fagherazzi, G and Loussikian, P and Marty, T and Mebarki, A and Texier, N and Schuck, S}, title = {Identifying Profiles and Symptoms of Patients With Long COVID in France: Data Mining Infodemiology Study Based on Social Media.}, journal = {JMIR infodemiology}, volume = {2}, number = {2}, pages = {e39849}, pmid = {36447795}, issn = {2564-1891}, abstract = {BACKGROUND: Long COVID-a condition with persistent symptoms post COVID-19 infection-is the first illness arising from social media. In France, the French hashtag #ApresJ20 described symptoms persisting longer than 20 days after contracting COVID-19. Faced with a lack of recognition from medical and official entities, patients formed communities on social media and described their symptoms as long-lasting, fluctuating, and multisystemic. While many studies on long COVID relied on traditional research methods with lengthy processes, social media offers a foundation for large-scale studies with a fast-flowing outburst of data.

OBJECTIVE: We aimed to identify and analyze Long Haulers' main reported symptoms, symptom co-occurrences, topics of discussion, difficulties encountered, and patient profiles.

METHODS: Data were extracted based on a list of pertinent keywords from public sites (eg, Twitter) and health-related forums (eg, Doctissimo). Reported symptoms were identified via the MedDRA dictionary, displayed per the volume of posts mentioning them, and aggregated at the user level. Associations were assessed by computing co-occurrences in users' messages, as pairs of preferred terms. Discussion topics were analyzed using the Biterm Topic Modeling; difficulties and unmet needs were explored manually. To identify patient profiles in relation to their symptoms, each preferred term's total was used to create user-level hierarchal clusters.

RESULTS: Between January 1, 2020, and August 10, 2021, overall, 15,364 messages were identified as originating from 6494 patients of long COVID or their caregivers. Our analyses revealed 3 major symptom co-occurrences: asthenia-dyspnea (102/289, 35.3%), asthenia-anxiety (65/289, 22.5%), and asthenia-headaches (50/289, 17.3%). The main reported difficulties were symptom management (150/424, 35.4% of messages), psychological impact (64/424,15.1%), significant pain (51/424, 12.0%), deterioration in general well-being (52/424, 12.3%), and impact on daily and professional life (40/424, 9.4% and 34/424, 8.0% of messages, respectively). We identified 3 profiles of patients in relation to their symptoms: profile A (n=406 patients) reported exclusively an asthenia symptom; profile B (n=129) expressed anxiety (n=129, 100%), asthenia (n=28, 21.7%), dyspnea (n=15, 11.6%), and ageusia (n=3, 2.3%); and profile C (n=141) described dyspnea (n=141, 100%), and asthenia (n=45, 31.9%). Approximately 49.1% of users (79/161) continued expressing symptoms after more than 3 months post infection, and 20.5% (33/161) after 1 year.

CONCLUSIONS: Long COVID is a lingering condition that affects people worldwide, physically and psychologically. It impacts Long Haulers' quality of life, everyday tasks, and professional activities. Social media played an undeniable role in raising and delivering Long Haulers' voices and can potentially rapidly provide large volumes of valuable patient-reported information. Since long COVID was a self-titled condition by patients themselves via social media, it is imperative to continuously include their perspectives in related research. Our results can help design patient-centric instruments to be further used in clinical practice to better capture meaningful dimensions of long COVID.}, } @article {pmid36447641, year = {2023}, author = {Damant, RW and Rourke, L and Cui, Y and Lam, GY and Smith, MP and Fuhr, DP and Tay, JK and Varughese, RA and Laratta, CR and Lau, A and Wong, EY and Stickland, MK and Ferrara, G}, title = {Reliability and validity of the post COVID-19 condition stigma questionnaire: A prospective cohort study.}, journal = {EClinicalMedicine}, volume = {55}, number = {}, pages = {101755}, pmid = {36447641}, issn = {2589-5370}, abstract = {BACKGROUND: Many of the 10-20% percent of COVID-19 survivors who develop Post COVID-19 Condition (PCC, or Long COVID) describe experiences suggestive of stigmatization, a known social determinant of health. Our objective was to develop an instrument, the Post COVID-19 Condition Stigma Questionnaire (PCCSQ), with which to quantify and characterise PCC-related stigma.

METHODS: We conducted a prospective cohort study to assess the reliability and validity of the PCCSQ. Patients referred to our Post COVID-19 Clinic in the Canadian City of Edmonton, Alberta between May 29, 2021 and May 24, 2022 who met inclusion criteria (attending an academic post COVID-19 clinic; age ≥18 years; persistent symptoms and impairment at ≥ 12 weeks since PCR positive acute COVID-19 infection; English-speaking; internet access; consenting) were invited to complete online questionnaires, including the PCCSQ. Analyses were conducted to estimate the instrument's reliability, construct validity, and association with relevant instruments and defined health outcomes.

FINDINGS: Of the 198 patients invited, 145 (73%) met inclusion criteria and completed usable questionnaires. Total Stigma Score (TSS) on the PCCSQ ranged from 40 to 174/200. The mean (SD) was 103.9 (31.3). Cronbach's alpha was 0.97. Test-retest reliability was 0.92. Factor analysis supported a 6-factor latent construct. Subtest reliabilities were >0.75. Individuals reporting increased TSS occurred across all demographic groups. Increased risk categories included women, white ethnicity, and limited educational opportunities. TSS was positively correlated with symptoms, depression, anxiety, loneliness, reduced self-esteem, thoughts of self-harm, post-COVID functional status, frailty, EQ5D5L score, and number of ED visits. It was negatively correlated with perceived social support, 6-min walk distance, and EQ5D5L global rating. Stigma scores were significantly increased among participants reporting employment status as disabled.

INTERPRETATION: Our findings suggested that the PCCSQ is a valid, reliable tool with which to estimate PCC-related stigma. It allows for the identification of patients reporting increased stigma and offers insights into their experiences.

FUNDING: The Edmonton Post COVID-19 Clinic is supported by the University of Alberta and Alberta Health Services. No additional sources of funding were involved in the execution of this research study.}, } @article {pmid36447237, year = {2022}, author = {Nugawela, MD and Stephenson, T and Shafran, R and De Stavola, BL and Ladhani, SN and Simmons, R and McOwat, K and Rojas, N and Dalrymple, E and Cheung, EY and Ford, T and Heyman, I and Crawley, E and Pinto Pereira, SM}, title = {Predictive model for long COVID in children 3 months after a SARS-CoV-2 PCR test.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {465}, pmid = {36447237}, issn = {1741-7015}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Child ; Humans ; Adolescent ; *SARS-CoV-2/genetics ; *COVID-19/diagnosis ; Quality of Life ; Polymerase Chain Reaction ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status.

METHODS: Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11-17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting.

RESULTS: A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130).

CONCLUSIONS: We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.}, } @article {pmid36446465, year = {2022}, author = {Ghossein-Doha, C and Wintjens, MSJN and Janssen, EBNJ and Klein, D and Heemskerk, SCM and Asselbergs, FW and Birnie, E and Bonsel, GJ and van Bussel, BCT and Cals, JWL and Ten Cate, H and Haagsma, J and Hemmen, B and van der Horst, ICC and Kietselaer, BLJH and Klok, FA and de Kruif, MD and Linschoten, M and van Santen, S and Vernooy, K and Willems, LH and Westerborg, R and Warle, M and van Kuijk, SMJ}, title = {Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.}, journal = {BMJ open}, volume = {12}, number = {11}, pages = {e065142}, pmid = {36446465}, issn = {2044-6055}, mesh = {Humans ; Cohort Studies ; *COVID-19/epidemiology ; Follow-Up Studies ; Prevalence ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

TRIAL REGISTRATION NUMBER: NCT05240742.}, } @article {pmid36446075, year = {2023}, author = {Patoulias, D and Dimosiari, A and Michailidis, T}, title = {Coronary microvascular dysfunction in the context of long COVID-19: What is the effect of anti-inflammatory treatment?.}, journal = {Kardiologia polska}, volume = {81}, number = {3}, pages = {318-319}, doi = {10.33963/KP.a2022.0272}, pmid = {36446075}, issn = {1897-4279}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Coronary Artery Disease ; *Myocardial Ischemia ; Coronary Circulation ; Coronary Vessels ; }, } @article {pmid36445566, year = {2023}, author = {Ferrara, MC and Zarcone, C and Tassistro, E and Rebora, P and Rossi, E and Luppi, F and Foti, G and Squillace, N and Lettino, M and Strepparava, MG and Bonfanti, P and Bellelli, G and , }, title = {Frailty and long-COVID: is COVID-19 responsible for a transition in frailty status among older adults who survived hospitalization for COVID-19?.}, journal = {Aging clinical and experimental research}, volume = {35}, number = {2}, pages = {455-461}, pmid = {36445566}, issn = {1720-8319}, mesh = {Aged ; Humans ; Male ; Female ; *COVID-19/epidemiology ; *Frailty ; Frail Elderly ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Hospitalization ; Geriatric Assessment ; }, abstract = {BACKGROUND: There is a paucity of knowledge about the effects of COronaVIrus Disease-19 (COVID-19) on long-term frailty development or progression over time.

AIM: This study aims to assess transitions in frailty status in older adults who survived hospitalization for COVID-19.

METHODS: This is a longitudinal panel study. A multidisciplinary outpatient follow-up service was established since summer 2020, for the evaluation of individuals discharged alive, after hospitalization due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the clinical frailty scale (CFS). Main patients' characteristics, including health, functional, cognitive, and psychological status were collected.

RESULTS: A total of 177 patients aged 65 years and older were evaluated until June 2022. They were predominantly male, with a median age of 70 (Q1-Q3 67-75) years and a median body mass index of 27.5 (Q1-Q3 24.9-30.6) kg/m[2] at hospital admission. The median follow-up time was 6.3 (Q1-Q3 3.7-10.9) months. Sixty-one patients (34.5%) scored worse at CFS follow-up compared to hospital admission, and twenty-two patients (12.4%) became frail.

DISCUSSION AND CONCLUSION: This study shows that one out of three older patients previously hospitalized for COVID-19 had an unfavorable transition in CFS score during a median follow-up of nearly 6 months. Specific interventions to prevent frailty development or progression should be considered for patients at risk. Further studies are required to confirm our findings.}, } @article {pmid36445225, year = {2023}, author = {Prayer, F and Kienast, P and Strassl, A and Moser, PT and Bernitzky, D and Milacek, C and Gyöngyösi, M and Kifjak, D and Röhrich, S and Beer, L and Watzenböck, ML and Milos, RI and Wassipaul, C and Gompelmann, D and Herold, CJ and Prosch, H and Heidinger, BH}, title = {Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.}, journal = {Radiology}, volume = {307}, number = {1}, pages = {e222087}, pmid = {36445225}, issn = {1527-1315}, mesh = {Male ; Adult ; Humans ; Middle Aged ; Prospective Studies ; Phantoms, Imaging ; *Photons ; *COVID-19/diagnostic imaging ; Tomography, X-Ray Computed/methods ; Lung/diagnostic imaging ; }, abstract = {Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [P < .001] and -1.15 ± 0.43 [P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.}, } @article {pmid36440302, year = {2022}, author = {Laranjeira, TA and Menezes, AS}, title = {A Systematic Review of Post-COVID Electrocardiographic Changes in Young Athletes.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e31829}, pmid = {36440302}, issn = {2168-8184}, abstract = {Post-coronavirus disease (COVID) syndrome involves the presentation of various new, returning, or ongoing symptoms, more than four weeks after COVID-19 infection. Post-infectious myocarditis is a potential sequela, associated with greater arrhythmogenic potential. Thus, it is an outcome that should be considered in athletes. An undiagnosed heart condition associated with adrenergic stimulus caused by high-intensity exercises can lead to sudden cardiac death. Electrocardiography (ECG) plays a role in cardiac screening for potential cardiac changes associated with myocarditis. Therefore, this study aimed to evaluate the occurrence of electrocardiographic alterations in athletes during the post-COVID period. A systematic review of longitudinal observational studies in the PubMed, LILACS, and CENTRAL databases that evaluated athletes in the post-COVID period with ECG was performed. A total of four articles involving 5371 patients were included in the analysis. The athletes mostly presented with mild asymptomatic or symptomatic COVID-19. A low prevalence of electrocardiographic alterations suggestive of cardiac involvement by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in this population. Electrocardiographic abnormalities indicative of myocarditis are uncommon in young athletes throughout the post-COVID era. However, anomalies that may signify and need further cardiovascular testing were found.}, } @article {pmid36438042, year = {2022}, author = {Romero-Rodríguez, E and Pérula-de Torres, LÁ and Castro-Jiménez, R and González-Lama, J and Jiménez-García, C and González-Bernal, JJ and González-Santos, J and Vélez-Santamaría, R and Sánchez-González, E and Santamaría-Peláez, M}, title = {Hospital admission and vaccination as predictive factors of long COVID-19 symptoms.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1016013}, pmid = {36438042}, issn = {2296-858X}, abstract = {BACKGROUND: Since the beginning of the COVID-19 pandemic, a great variability of symptoms that affect all organs and systems of the body has been identified in patients with SARS-CoV-2 infection; this symptomatology can sometimes persist over time, giving rise to the so-called long COVID or post-COVID. The aim of this study is to delve into the clinical characterization of these patients, as well as to take into account the influence of factors such as hospitalization, admission to ICU, history of pneumonia, or vaccination status on the persistence of symptoms.

MATERIAL AND METHODS: An observational, descriptive, multicenter, and retrospective study was designed with a series of cases of people who presented long COVID, which includes univariate, bivariate, and multivariate analyses. Data were obtained from an online ad hoc questionnaire, and statistical analysis was performed using SPSS Software Version 25 (IBM-Inc., Chicago, IL, USA).

RESULTS: Hospitalization, ICU admission, history of pneumonia, and vaccination were predictive factors (positive or negative) for the following long-COVID symptoms: headache, menstrual disorders, joint pain, cough, chills, nasal congestion, back pain, abdominal pain, weight loss, eye discomfort, facial erythema, itching, tremors, dizziness, seizures, sleeping difficulty, dry eyes, palpitations, fatigue, paresthesia, dyspnea, aphonia, chest pain, high blood pressure, vomiting, memory loss, brain fog, hypothermia, low blood pressure, sputum or phlegm, lack of concentration, hair loss, and erectile dysfunction.

CONCLUSION: This study provides evidence on the clinical characterization of patients suffering from long COVID in order to offer them the most appropriate treatments.}, } @article {pmid36437985, year = {2022}, author = {Chang, JG and Ha, EH and Lee, W and Lee, SY}, title = {Cognitive impairments in patients with subacute coronavirus disease: Initial experiences in a post-coronavirus disease clinic.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {994331}, pmid = {36437985}, issn = {1663-4365}, abstract = {BACKGROUND: A significant number of patients experience persistent cognitive impairment after coronavirus disease (COVID-19). This study aimed to investigate the cognitive function of patients in the subacute phase of COVID-19 and to identify the clinical factors associated with cognitive sequelae.

MATERIALS AND METHODS: Data from patients who visited the psychiatric department of our post-COVID clinic between March and May 2022 were analyzed. The results of neuropsychiatric function tests, including the digit span forward (attention/processing speed) and backward (working memory) tests, the trail making test part A (attention/processing speed) and part B (executive functioning), and the Stroop word color interference test (executive functioning), as well as clinical data from 40 patients in the subacute phase of COVID-19 were analyzed. We calculated the frequency of impairments in each cognitive measure, defined as a z-score of ≤-1.5 standard deviations below measure-specific age- and sex-adjusted norms.

RESULTS: Of the participants, 72.5% (n = 29) had impairments in at least one cognitive domain. Impairment in executive function was the most frequent (64.9%), followed by impairments in processing speed/attention (52.5%) and working memory (42.5%). Age was inversely correlated with T scores in all cognitive function tests.

CONCLUSION: Regular examination of cognitive function is needed, especially in elderly individuals, regardless of the subjective symptom manifestations.}, } @article {pmid36436792, year = {2023}, author = {Huang, Q and Jia, M and Sun, Y and Jiang, B and Cui, D and Feng, L and Yang, W}, title = {One-Year Temporal Changes in Long COVID Prevalence and Characteristics: A Systematic Review and Meta-Analysis.}, journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research}, volume = {26}, number = {6}, pages = {934-942}, doi = {10.1016/j.jval.2022.11.011}, pmid = {36436792}, issn = {1524-4733}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; *Mental Disorders ; Risk Factors ; }, abstract = {OBJECTIVES: This study aimed to explore the 1-year temporal change in prevalence, variety, and potential risk factors of long COVID symptoms and to further predict the prognostic trends of long COVID.

METHODS: We searched electronic databases for related studies published from January 2020 to February 2022 and conducted 1-group meta-analysis and locally weighted regression to explore the monthly temporal change in the prevalence of each long COVID symptom in 1-year follow-up period.

RESULTS: A total of 137 studies were included in meta-analysis, including 134 093 participants. The temporal change of any long COVID symptom showed a steep decrease initially (from 92% at acute phase to 55% at 1-month follow-up), followed by stabilization at approximately 50% during 1-year follow-up. Six months or more after the acute phase, the odds ratio of population characteristic-related factors increased, such as female (from 1.62 to 1.82), whereas the odds ratio value of acute phase-related factors (severe or critical cases and hospitalization) decreased. As for specific symptoms, approximately two-thirds of the symptoms did not significantly reduce during the 1-year follow-up, and the neuropsychiatric symptoms showed a higher long-term prevalence (approximately 25%) and longer persistence than physical symptoms.

CONCLUSIONS: The temporal changes in the prevalence and characteristics speculate that long COVID may persist longer than expected. In particular, we should pay more attention to neuropsychiatric symptoms and other symptoms for which there is no significant downward trend in prevalence. The influence of acute phase-related factors for long COVID gradually decreases over time, whereas the influence of population characteristic-related factors gradually increases.}, } @article {pmid36435560, year = {2022}, author = {Qanneta, R}, title = {Long COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: Similarities and differences of two peas in a pod.}, journal = {Reumatologia clinica}, volume = {18}, number = {10}, pages = {626-628}, pmid = {36435560}, issn = {2173-5743}, mesh = {Humans ; *Fatigue Syndrome, Chronic/diagnosis ; *COVID-19 ; Fatigue ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36434908, year = {2022}, author = {Baruch, J and Zahra, C and Cardona, T and Melillo, T}, title = {National long COVID impact and risk factors.}, journal = {Public health}, volume = {213}, number = {}, pages = {177-180}, pmid = {36434908}, issn = {1476-5616}, mesh = {Humans ; Female ; Adult ; Infant ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Risk Factors ; Memory Disorders ; }, abstract = {OBJECTIVE: Our objective was to estimate the prevalence and risk factors for long COVID symptoms among polymerase chain reaction-confirmed COVID-19 patients (hospitalised and community) in Malta.

STUDY DESIGN: This was a national cross-sectional survey among COVID-19 patients in Malta during 2020.

METHODS: Patients were sent a questionnaire 3-6 months after testing positive. Data were analysed descriptively to estimate symptom prevalence, and multivariable logistic regressions were used to determine the risk factors for long COVID symptoms. Age, sex, initial symptoms, hospitalisation, and healthcare worker status were used as risk factors and symptoms (cough, shortness of breath, fatigue, anxiety, sadness, and memory loss) 2.5 months or more after COVID-19 onset were used as outcomes.

RESULTS: Of 8446 eligible participants, 2665 (31.55%) responded with a median age of 37 years. Initial symptoms were reported in 82% of responders, and 7.73% were hospitalised. Among the long COVID symptoms, fatigue persisted among most non-hospitalised responders, whereas anxiety, shortness of breath, and sadness were the most common symptoms. Female sex, hospitalisation, and initial symptoms were associated with higher odds of fatigue, shortness of breath, cough, anxiety, sadness, and memory loss as long COVID symptoms.

CONCLUSIONS: Our study is the first to highlight long COVID symptoms and risk factors in Malta, showing that long COVID is common among hospitalised and non-hospitalised patients. These data should increase awareness of long COVID and facilitate support to those affected nationally.}, } @article {pmid36434150, year = {2022}, author = {Zhang, L and Lei, J and Zhang, J and Yin, L and Chen, Y and Xi, Y and Moreira, JP}, title = {Undiagnosed Long COVID-19 in China Among Non-vaccinated Individuals: Identifying Persistent Symptoms and Impacts on Patients' Health-Related Quality of Life.}, journal = {Journal of epidemiology and global health}, volume = {12}, number = {4}, pages = {560-571}, pmid = {36434150}, issn = {2210-6014}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Quality of Life ; China/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Is Long COVID-19 under-diagnosed? The definition of this new condition has received many contributions, and it is still under development as a great variety of symptoms have been associated to it. This study explores the possibility that there are non-diagnosed cases among individuals who have been infected by SARS-CoV-2 and have not been vaccinated. The long-term symptoms identified among a sample 255 individuals have been associated to Long COVID-19 by recent literature. The study relates these symptoms to risk factors and health-related quality of life (HRQoL) negative impacts. The individuals were screened 1 year after discharge to explore its potential relation to Long COVID-19. Patients diagnosed with COVID-19 and discharged from designated hospitals in a Chinese province between January and April 2020 were included in this study. They received computed tomography (CT) scans one month after discharge. One year after discharge, patients were invited to physical examination and interviewed with questionnaire on health-related quality of life (HRQoL) and post-COVID-19 symptoms. Tobit regression and Logistic regression were applied to evaluate the risk factors for health utility value and pain/discomfort and anxiety/depression. One year after discharge, 39.61% patients complained of several of the symptoms associated to Long COVID-19. More than half had abnormal chest CT. Previous studies focused on the post-COVID-19 symptoms and chest CT findings of patients, but few studies have assessed the COVID-19-associated risk factors for health-related quality of life.}, } @article {pmid36432196, year = {2022}, author = {Henri, J and Minder, L and Mohanasundaram, K and Dilly, S and Goupil-Lamy, A and Di Primo, C and Slama Schwok, A}, title = {Neuropeptides, New Ligands of SARS-CoV-2 Nucleoprotein, a Potential Link between Replication, Inflammation and Neurotransmission.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {22}, pages = {}, pmid = {36432196}, issn = {1420-3049}, support = {CoVNucleovir//The CovNucleovir from the faculty of Medicine of Sorbonne University/ ; CoVNucleovir//The Sorbonne University Foundation/ ; }, mesh = {Humans ; Nucleoproteins ; SARS-CoV-2 ; *COVID-19 ; Ligands ; Substance P ; *Neuropeptides ; Synaptic Transmission ; Inflammation ; Post-Acute COVID-19 Syndrome ; }, abstract = {This work identifies new ligands of the nucleoprotein N of SARS-CoV-2 by in silico screening, which used a new model of N, built from an Alphafold model refined by molecular dynamic simulations. The ligands were neuropeptides, such as substance P (1-7) and enkephalin, bound at a large site of the C-terminal or associated with the N-terminal β-sheet. The BA4 and BA5 Omicron variants of N also exhibited a large site as in wt N, and an increased flexibility of the BA5 variant, enabling substance P binding. The binding sites of some ligands deduced from modeling in wt N were assessed by mutation studies in surface plasmon resonance experiments. Dynamic light scattering showed that the ligands impeded RNA binding to N, which likely inhibited replication. We suggest that the physiological role of these neuropeptides in neurotransmission, pain and vasodilation for cholecystokinin and substance P could be altered by binding to N. We speculate that N may link between viral replication and multiple pathways leading to long COVID-19 symptoms. Therefore, N may constitute a "danger hub" that needs to be inhibited, even at high cost for the host. Antivirals targeted to N may therefore reduce the risk of brain fog and stroke, and improve patients' health.}, } @article {pmid36431250, year = {2022}, author = {Buonsenso, D and Pazukhina, E and Gentili, C and Vetrugno, L and Morello, R and Zona, M and De Matteis, A and D'Ilario, F and Lanni, R and Rongai, T and Del Balzo, P and Fonte, MT and Valente, M and De Rose, C and Munblit, D and Sigfrid, L and Valentini, P}, title = {The Prevalence, Characteristics and Risk Factors of Persistent Symptoms in Non-Hospitalized and Hospitalized Children with SARS-CoV-2 Infection Followed-Up for up to 12 Months: A Prospective, Cohort Study in Rome, Italy.}, journal = {Journal of clinical medicine}, volume = {11}, number = {22}, pages = {}, pmid = {36431250}, issn = {2077-0383}, abstract = {Previous studies assessing the prevalence of COVID-19 sequelae in children have included either a small number of children or a short follow-up period, or have only focused on hospitalized children. We investigated the prevalence of persistent symptoms amongst children and assessed the risk factors, including the impact of variants. A prospective cohort study included children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection. The participants were assessed via telephone and face-to-face visits at 1-5, 6-9 and 12 or more months post-SARS-CoV-2 diagnosis using the ISARIC COVID-19 follow-up survey. Of the 679 children enrolled, 51% were female; 488 were infected during the wild virus wave, and 29 were infected with the Alpha, 42 with the Delta and 120 with the Omicron variants. Fatigue (19%), headache (12%), insomnia (7.5%), muscle pain (6.9%) and confusion with concentration issues (6.8%) were the most common persistent symptoms. Families reported an overall improvement over time, with 0.7% of parents interviewed at 12 months or more of the follow-up period reporting a poor recovery. Patients that had not recovered by 6-9 months had a lower probability of recovering during the next follow-up period. Children infected with a variant or the wild virus had an overall similar rate of persistent symptoms (although the pattern of reported symptoms differed significantly) and recovery rates. Conclusions: Recovery rates after SARS-CoV-2 infection improved as time passed from the initial infection, ranging from 4% of children having poor recovery at 1-5 months' follow-up to 1.3% at 6-9 months and 0.7% at 12 months. The patterns of persistence changed according to the variants involved at the time of infection. This study reinforces that a subgroup of children develop long-lasting persistent symptoms and highlights the need for further studies investigating the reasons behind the development of PCC.}, } @article {pmid36430303, year = {2022}, author = {Huang, S and Taylor, CG and Zahradka, P}, title = {Long Chain N3-PUFA Decreases ACE2 Protein Levels and Prevents SARS-CoV-2 Cell Entry.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430303}, issn = {1422-0067}, support = {Research Without Borders//St. Boniface Hospital Foundation/ ; }, mesh = {Animals ; Humans ; Rats ; Angiotensin-Converting Enzyme 2 ; *COVID-19 ; Docosahexaenoic Acids/pharmacology ; *Fatty Acids, Omega-3/pharmacology ; HEK293 Cells ; SARS-CoV-2 ; Virus Internalization ; }, abstract = {Angiotensin-converting enzyme 2 (ACE2) is a target of interest for both COVID-19 and cardiovascular disease management. Even though lower ACE2 levels may be beneficial in SARS-CoV-2 infectivity, maintaining the ACE1/ACE2 balance is also crucial for cardiovascular health. So far, reports describing conditions capable of altering ACE2 protein levels, especially via dietary components, are limited. In this study, the effects of omega-3 polyunsaturated fatty acids (n3-PUFA) on the protein levels of ACE1 and ACE2 in rodent tissues, human endothelial and kidney cell lines, and human plasma were examined. The ability of n3-PUFA to affect the entry of the SARS-CoV-2 pseudovirus into cells was also tested. Docosahexaenoic acid (DHA), and in some cases eicosapentaenoic acid (EPA), but not α-linoleic acid (ALA), reduced both ACE1 and ACE2 (non-glycosylated p100 and glycosylated p130 forms) in the heart, aorta, and kidneys of obese rats, as well as in human EA.hy926 endothelial and HEK293 kidney cells. Dietary supplementation with either DHA or ALA had no effect on plasma soluble ACE2 levels in humans. However, treatment of HEK293 cells with 80 and 125 µM DHA for 16 h inhibited the entry of the SARS-CoV-2 pseudovirus. These results strongly suggest that DHA treatment may reduce the ability of SARS-CoV-2 to infect cells via a mechanism involving a decrease in the absolute level of ACE2 protein as well as its glycosylation. Our findings warrant further evaluation of long-chain n3-PUFA supplements as a novel option for restricting SARS-CoV-2 infectivity in the general population.}, } @article {pmid36430175, year = {2022}, author = {Schlick, S and Lucio, M and Wallukat, G and Bartsch, A and Skornia, A and Hoffmanns, J and Szewczykowski, C and Schröder, T and Raith, F and Rogge, L and Heltmann, F and Moritz, M and Beitlich, L and Schottenhamml, J and Herrmann, M and Harrer, T and Ganslmayer, M and Kruse, FE and Lämmer, R and Mardin, C and Hohberger, B}, title = {Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430175}, issn = {1422-0067}, support = {LGL; 2490-PC-2021-V14//Bavarian Health and Food Safety Authority/ ; }, mesh = {Humans ; Male ; Female ; Fluorescein Angiography/methods ; *COVID-19/complications ; Retinal Vessels ; Microcirculation ; Tomography, Optical Coherence/methods ; Prospective Studies ; *Fatigue Syndrome, Chronic ; SARS-CoV-2 ; Fatigue ; Biomarkers ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.}, } @article {pmid36429623, year = {2022}, author = {McEwan, K and Collett, H and Nairn, J and Bird, J and Faghy, MA and Pfeifer, E and Jackson, JE and Cook, C and Bond, A}, title = {The Feasibility and Impact of Practising Online Forest Bathing to Improve Anxiety, Rumination, Social Connection and Long-COVID Symptoms: A Pilot Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {22}, pages = {}, pmid = {36429623}, issn = {1660-4601}, mesh = {Adult ; Humans ; Pilot Projects ; *COVID-19/epidemiology ; Feasibility Studies ; Anxiety/therapy ; Forests ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID affects over 144 million people globally. In the absence of treatments, there is a need to establish the efficacy of therapies that improve patient outcomes. Forest bathing has been demonstrated to improve physical and mental outcomes but there is no evidence in Long-COVID patients. Accordingly, this pilot study sought to determine the feasibility and effectiveness of online forest bathing in adults with Long-COVID.

METHODS: Feasibility was assessed by monitoring retention rates and participant feedback. In a waitlist controlled, repeated measures design, 22 Long-COVID patients completed weekly online surveys during a four-week waitlist control period, before engaging in four weekly online forest bathing sessions, completing post-intervention surveys following each session.

RESULTS: In terms of retention, 27% did not provide post-intervention data, reasons for non-adherence were: feeling too ill, having medical appointments, or having career responsibilities. Compared with the waitlist control period, there were statistically significant improvements in Anxiety (49% decrease), Rumination (48% decrease), Social Connection (78% increase), and Long-COVID symptoms (22% decrease). Written qualitative comments indicated that participants experienced feelings of calm and joy, felt more connected socially and with nature, and experienced a break from the pain and rumination surrounding their illness.

CONCLUSIONS: Online Forest bathing resulted in significant improvements in well-being and symptom severity and could be considered an accessible and inexpensive adjunct therapy for Long-COVID patients. Where people have limited access to in-person nature, virtual nature may offer an alternative to improve health and well-being outcomes.}, } @article {pmid36429458, year = {2022}, author = {Nielsen, TB and Leth, S and Pedersen, M and Harbo, HD and Nielsen, CV and Laursen, CH and Schiøttz-Christensen, B and Oestergaard, LG}, title = {Mental Fatigue, Activities of Daily Living, Sick Leave and Functional Status among Patients with Long COVID: A Cross-Sectional Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {22}, pages = {}, pmid = {36429458}, issn = {1660-4601}, mesh = {Humans ; Female ; Middle Aged ; Adolescent ; Male ; *Sick Leave ; Activities of Daily Living ; Cross-Sectional Studies ; *COVID-19/epidemiology ; Functional Status ; Canada ; Mental Fatigue/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Studies suggest that persistent symptoms after COVID-19 (long COVID) influence functioning and activities of daily living (ADL). However, it is still uncertain how and to what extent. This study aimed to describe patient-reported mental fatigue, ADL problems, ADL ability, sick leave and functional status among patients with long COVID. In this cross-sectional study, 448 patients, ≥18 years old and referred to occupational therapy at a Danish Post-COVID-19 Clinic, were included. Mental fatigue was measured by the Mental Fatigue Scale, ADL problems and ability were measured by the Canadian Occupational Performance Measure, sick leave was self-reported and functional status was evaluated by the Post-COVID-19 Functional Status Scale. Mean age was 46.8 years, 73% of the patients were female, and 75% suffered from moderate to severe mental fatigue. The majority reported difficulties performing productive and leisure activities. The median performance and satisfaction scores were 4.8 and 3, respectively. In total, 56% of the patients were on sick leave, and 94% were referred to rehabilitation. A decrease in functional status was found between pre-COVID-19 and assessment. Conclusively, the patients were highly affected in their everyday life and had distinct rehabilitation needs. Future research is needed to address causalities and rehabilitation for this patient group.}, } @article {pmid36429392, year = {2022}, author = {Izquierdo-Condoy, JS and Fernandez-Naranjo, R and Vasconez-González, E and Cordovez, S and Tello-De-la-Torre, A and Paz, C and Delgado-Moreira, K and Carrington, S and Viscor, G and Ortiz-Prado, E}, title = {Long COVID at Different Altitudes: A Countrywide Epidemiological Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {22}, pages = {}, pmid = {36429392}, issn = {1660-4601}, mesh = {Young Adult ; Humans ; Female ; *Altitude ; *COVID-19/epidemiology ; Cross-Sectional Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients.

METHODS: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (<2500 m) and high altitude (>2500 m).

RESULTS: Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses.

CONCLUSIONS: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.}, } @article {pmid36427058, year = {2022}, author = {Pintos-Pascual, I and Moreno-Torres, V and Ibánez-Estéllez, F and Corrales-Rodriguez, P and Treviño, A and Corpas, M and Corral, O and Soriano, V and de Mendoza, C}, title = {Is SARS-CoV-2 the only cause of long-COVID?.}, journal = {AIDS reviews}, volume = {24}, number = {4}, pages = {183-196}, doi = {10.24875/AIDSRev.22000025}, pmid = {36427058}, issn = {1698-6997}, mesh = {Adult ; Male ; Humans ; Female ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *COVID-19/complications ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; *HIV Infections ; Post-Infectious Disorders ; }, abstract = {Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved. There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of postinfectious fatigue syndromes.}, } @article {pmid36426658, year = {2024}, author = {Rochmawati, E and Iskandar, AC and Kamilah, F}, title = {Persistent symptoms among post-COVID-19 survivors: A systematic review and meta-analysis.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {29-39}, doi = {10.1111/jocn.16471}, pmid = {36426658}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/epidemiology ; Chest Pain ; Cough ; Dyspnea ; Fatigue/epidemiology ; }, abstract = {BACKGROUND: Single studies support the presence of several post-COVID-19 symptoms; however, there is no evidence for the synthesis of symptoms.

OBJECTIVE: We attempt to provide an overview of the persistent symptoms that post-COVID-19 patients encounter, as well as the duration of these symptoms to help them plan their rehabilitation.

DESIGN: Systematic review and meta-analysis.

PARTICIPANTS: A total of 16 studies involving 8756 patients post-COVID-19 were included.

METHODS: The CINAHL, PubMed, EMBASE, Scopus, and Web of Science databases were searched from 2019 to August 2021. Observational studies that reported data on post-COVID-19 symptoms were included. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal for Observational Studies. We included medium- to high-quality studies. We used a random-effects model for the meta-analytical pooled prevalence of each post-COVID-19 symptom, and I[2] statistics for heterogeneity.

RESULTS: From the 2481 studies identified, 16 met the inclusion criteria. The sample included 7623 hospitalised and 1133 non-hospitalised patients. We found the most prevalent symptoms were fatigue and dyspnea with a pooled prevalence ranging from 42% (27%-58%). Other post-COVID-19 symptoms included sleep disturbance 28% (14%-45%), cough 25% (10%-44%), anosmia/ageusia 24% (7%-47%), fever 21% (4%-47%), myalgia 17% (2%-41%), chest pain 11% (5%-20%), and headache 9% (2%-20%). In addition to physical symptoms, anxiety/depression was also prevalent 27% (8%-53%).

CONCLUSIONS: Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms and experienced up to 12 months.

Multiple persistent symptoms are still experienced until 12 months of post-Covid 19. This meta-analysis should provide some awareness to nurses to highlights the unmet healthcare needs of post-COVID-19 patients. Long-term monitoring for the evaluation and treatment of symptoms and conditions and rehabilitation programs should be conducted.}, } @article {pmid36425345, year = {2022}, author = {Gustavson, AM and Purnell, A and Adly, M and Awan, O and Bräu, N and Braus, NA and Bryant, MS and Chang, L and Cyborski, C and Darvish, B and Del Piero, LB and Eaton, TL and Kiliveros, A and Kloth, H and McNiel, ER and Miller, MA and Patrick, A and Powers, P and Pyne, M and Rodriguez, IG and Romesser, J and Rud, B and Seidel, I and Tepper, A and Trinh, H and Tonkin, B and Vachachira, J and Yang, H and Shak, JR}, title = {A Learning Health System Approach to Long COVID Care.}, journal = {Federal practitioner : for the health care professionals of the VA, DoD, and PHS}, volume = {39}, number = {7}, pages = {310-314}, pmid = {36425345}, issn = {1078-4497}, abstract = {BACKGROUND: Global initiatives to mitigate COVID-19 transmission have shifted health system priorities to management of patients with prolonged long COVID symptoms. To better meet the needs of patients, clinicians, and systems, a learning health system approach can use rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care.

OBSERVATIONS: Employees in the Veterans Health Administration formed a multidisciplinary workgroup. We sought to develop processes to learn more about this novel long COVID syndrome and innovative long COVID care models that can be applied within and outside of our health care system. We describe our workgroup processes and goals to create a mechanism for cross-facility communication, identify gaps in care and research, and cocreate knowledge on best practices for long COVID care delivery.

CONCLUSIONS: The learning health system approach will be critical in reimagining health care service delivery after the COVID-19 pandemic.}, } @article {pmid36425003, year = {2022}, author = {Thurner, L and Fadle, N and Regitz, E and Preuss, KD and Neumann, F and Cetin, O and Schormann, C and Hoffmann, MC and Herr, C and Kheiroddin, P and Rixecker, TM and Bals, R and Muller, S and Thurner, B and Kessel, C and Kabesch, M and Bewarder, M and Heyne, K and Lensch, C and Kos, IA}, title = {Autoantibodies against SUMO1-DHX35 in long-COVID.}, journal = {Journal of translational autoimmunity}, volume = {5}, number = {}, pages = {100171}, pmid = {36425003}, issn = {2589-9090}, abstract = {Long COVID is a collection of symptoms as a late sequelae of SARS-CoV-2 infection. It often includes mental symptoms such as cognitive symptoms, persisting loss of smell and taste, in addition to exertional dyspnea. A role of various autoantibodies (autoAbs) has been postulated in long-COVID and is being further investigated. With the goal of identifying potentially unknown autoAbs, we screened plasma of patients with long COVID on in-house post-translationally modified protein macroarrays including citrullinated, SUMOylated and acetylated membranes. SUMO1ylated isoform DEAD/H (Asp-Glu-Ala-Asp/His) box helicase 35 (SUMO1-DHX35) was identified as only candidate antigen. In adult patients with long COVID, IgG autoAbs against SUMO1-DHX35 of IgG class were found in seven of 71 (9.8%) plasma samples, of IgM and IgG class in one of 69 (1.4%) samples, not in 200 healthy adult controls, not in 442 healthy children, and 146 children after SARS-CoV-2 infection. All autoAb-positive seven patients were female. AutoAb titers ranged between 200 to up to 400 By point mutagenesis and expression of FLAG-tagged mutants of DHX35 in HEK293 cells, and subsequent SUMOylation of purified constructs, lysine 53 was identified as a unique, never yet identified, SUMOylation site. The autoAbs had no reactivity against the non-SUMO1ylated mutant (K53R) of DHX35. To summarize, autoAbs against SUMO1-DHX35 were identified in adult female patients with long-COVID. Further studies are needed to verify the frequency of occurrence. The function of DHX35 has not yet been determined and there is no available information in relation to disease implication. The molecular mechanism causing the SUMOylation, the potential functional consequences of this post-translational modification on DHX35, and a potential pathogenicity of the autoAbs against SUMO1-DHX35 in COVID-19 and other possible contexts remain to be elucidated.}, } @article {pmid36424958, year = {2022}, author = {Paul, S and Mishra, CM}, title = {Do we need to vaccinate every child against COVID-19: What evidence suggests-A systematic review of opinions.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1002992}, pmid = {36424958}, issn = {2296-2565}, mesh = {Systemic Inflammatory Response Syndrome ; Child ; Humans ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; *COVID-19/prevention & control/complications ; Adult ; Vaccination ; }, abstract = {It is still debatable whether all children should receive the COVID-19 vaccine. The comparatively mild cases and low risk of COVID-19 in children compared to adults, as well as the lack of clarity on the relative effects of the disease and vaccine, indicate that the risk-benefit ratio of vaccination in children is more nuanced. To consider and highlight the complexity of policy decisions regarding COVID-19 vaccination in children, we outlined the points regarding for and against vaccination of children against COVID-19 in this systemic review. Using Medical Search Headings (MeSH) terms and keywords, we searched PubMed, PubMed Central, Scopus, and Google Scholar. The primary search term was COVID-19 vaccination (all synonyms), factors (all synonyms), and among children (all synonyms). A total of 367 articles were searched. Finally, 64 articles met the inclusion criteria and were included in the review. The major theme/tone of 28 (43.75%) articles was in favor of children's COVID vaccination, and they were highlighting the positive factors, whereas the major theme/tone of 20 (31.25%) articles was against it. Approximately 16 (25.0%) articles were in a neutral position. Major factors highlighted by articles in favor of childhood COVID vaccination were as follows: the increasing rate of disease burden (29 articles), prevention of interruption of academic activities of children or school reopening (24 articles), and a role in defense against COVID infection (21 articles). Major factors against childhood vaccination were as follows: mild infection among children (27 articles), ethical concerns and legal problems regarding the consent of minors (17 articles), and vaccine hesitancy among parents for childhood vaccination (11 articles). Whereas, factors of uncertainty were the role in the reduction of community transmission (19 articles), protection against MIS-C (10 articles), and defense against long COVID (7 articles). Considering all the factors of COVID-19 disease progression among children, a cautious approach will be essential before proceeding with COVID-19 vaccination in children.}, } @article {pmid36423831, year = {2023}, author = {Faist, A and Schloer, S and Mecate-Zambrano, A and Janowski, J and Schreiber, A and Boergeling, Y and Conrad, BCG and Kumar, S and Toebben, L and Schughart, K and Baumgardt, M and Kessler, M and Hoenzke, K and Hocke, A and Trautmann, M and Hartmann, W and Kato, H and Rescher, U and Christersson, A and Kuehn, J and Mellmann, A and Wolff, T and Kuempers, P and Rovas, A and Wiewrodt, R and Wiebe, K and Barth, P and Ludwig, S and Brunotte, L}, title = {Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier.}, journal = {Antiviral research}, volume = {209}, number = {}, pages = {105475}, pmid = {36423831}, issn = {1872-9096}, support = {U19 AI100625/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Antiviral Agents/pharmacology/therapeutic use ; *COVID-19/complications ; *Inflammation/drug therapy/virology ; Lung ; *p38 Mitogen-Activated Protein Kinases ; *Post-Acute COVID-19 Syndrome ; *SARS-CoV-2 ; Signal Transduction ; }, abstract = {SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate that targeting p38 signal transduction with the selective and clinically pre-evaluated inhibitors PH-797804 and VX-702 markedly reduced the expression of the pro-inflammatory cytokines IL6, CXCL8, CXCL10 and TNF-α during infection, while viral replication and the interferon-mediated antiviral response of the lung epithelial barrier were largely maintained. Furthermore, our results reveal a high level of drug synergism of both p38 inhibitors in co-treatments with the nucleoside analogs Remdesivir and Molnupiravir to suppress viral replication of the SARS-CoV-2 variants of concern, revealing an exciting and novel mode of synergistic action of p38 inhibition. These results open new avenues for the improvement of the current treatment strategies for COVID-19.}, } @article {pmid36422588, year = {2022}, author = {Fernández-de-Las-Peñas, C and Liew, BXW and Herrero-Montes, M and Del-Valle-Loarte, P and Rodríguez-Rosado, R and Ferrer-Pargada, D and Neblett, R and Paras-Bravo, P}, title = {Data-Driven Path Analytic Modeling to Understand Underlying Mechanisms in COVID-19 Survivors Suffering from Long-Term Post-COVID Pain: A Spanish Cohort Study.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {36422588}, issn = {2076-0817}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; Next-Val 2021//Fundación Marques de Valdecilla/ ; }, abstract = {Pain can be present in up to 50% of people with post-COVID-19 condition. Understanding the complexity of post-COVID pain can help with better phenotyping of this post-COVID symptom. The aim of this study is to describe the complex associations between sensory-related, psychological, and cognitive variables in previously hospitalized COVID-19 survivors with post-COVID pain, recruited from three hospitals in Madrid (Spain) by using data-driven path analytic modeling. Demographic (i.e., age, height, and weight), sensory-related (intensity or duration of pain, central sensitization-associated symptoms, and neuropathic pain features), psychological (anxiety and depressive levels, and sleep quality), and cognitive (catastrophizing and kinesiophobia) variables were collected in a sample of 149 subjects with post-COVID pain. A Bayesian network was used for structural learning, and the structural model was fitted using structural equation modeling (SEM). The SEM model fit was excellent: RMSEA < 0.001, CFI = 1.000, SRMR = 0.063, and NNFI = 1.008. The only significant predictor of post-COVID pain was the level of depressive symptoms (β=0.241, p = 0.001). Higher levels of anxiety were associated with greater central sensitization-associated symptoms by a magnitude of β=0.406 (p = 0.008). Males reported less severe neuropathic pain symptoms (−1.50 SD S-LANSS score, p < 0.001) than females. A higher level of depressive symptoms was associated with worse sleep quality (β=0.406, p < 0.001), and greater levels of catastrophizing (β=0.345, p < 0.001). This study presents a model for post-COVID pain where psychological factors were related to central sensitization-associated symptoms and sleep quality. Further, maladaptive cognitions, such as catastrophizing, were also associated with depression. Finally, females reported more neuropathic pain features than males. Our data-driven model could be leveraged in clinical trials investigating treatment approaches in COVID-19 survivors with post-COVID pain and can represent a first step for the development of a theoretical/conceptual framework for post-COVID pain.}, } @article {pmid36420736, year = {2023}, author = {Zhang, HP and Sun, YL and Wang, YF and Yazici, D and Azkur, D and Ogulur, I and Azkur, AK and Yang, ZW and Chen, XX and Zhang, AZ and Hu, JQ and Liu, GH and Akdis, M and Akdis, CA and Gao, YD}, title = {Recent developments in the immunopathology of COVID-19.}, journal = {Allergy}, volume = {78}, number = {2}, pages = {369-388}, pmid = {36420736}, issn = {1398-9995}, mesh = {*COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Anaphylaxis ; }, abstract = {There has been an important change in the clinical characteristics and immune profile of Coronavirus disease 2019 (COVID-19) patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy of the COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4, and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) may cause severe and heterogeneous disease but with a lower mortality rate. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. There is conflicting evidence about whether atopic diseases, such as allergic asthma and rhinitis, are associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, the European Academy of Allergy and Clinical Immunology (EAACI) developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID-19.}, } @article {pmid36420354, year = {2022}, author = {Agarwala, S and Vijayvargiya, M and Sawant, T and Kulkarni, S}, title = {Bisphosphonates for Post-COVID Osteonecrosis of the Femoral Head: Medical Management of a Surgical Condition.}, journal = {JB & JS open access}, volume = {7}, number = {4}, pages = {}, pmid = {36420354}, issn = {2472-7245}, abstract = {UNLABELLED: COVID-19 infection can cause long-term effects, cumulatively known as long COVID syndrome. One such sequela is osteonecrosis of the femoral head (also called avascular necrosis of the femoral head, or AVNFH). On the basis of our 20-year experience in using bisphosphonate therapy in the successful management of osteonecrosis, we conducted the present study to evaluate the efficacy of the therapy in the management of post-COVID osteonecrosis of the femoral head. In addition, we aimed to evaluate the cumulative dosage of corticosteroids and the duration between the commencement of corticosteroids and the development of osteonecrosis in COVID-19 survivors.

METHODS: This was a retrospective evaluation of 48 patients (88 hips) diagnosed with osteonecrosis of the femoral head at a tertiary care center after COVID-19 infection between September 2020 and May 2021. Patients received intravenous zoledronic acid (5 mg) at the initiation of therapy and oral alendronate (35 mg) twice weekly, and were followed for a minimum of 6 months. Clinical evaluation was conducted using a visual analog scale (VAS) for pain and the Harris hip score (HHS). Radiographic evaluation was performed to assess the progression of the disease and collapse of the femoral head.

RESULTS: At a mean follow-up of 10 months, 84 (95.5%) of the hips showed good clinical outcomes, and only 4 (4.5%) of the hips required surgical intervention. The mean VAS pain score and HHS improved at 6 weeks and steadily improved on subsequent follow-ups. In 16 (18%) of the 88 affected hips, radiographic progression was observed. The mean dose of corticosteroids administered to the patients to manage COVID-19 infection was 841.3 mg of prednisolone equivalents. The mean duration between the commencement of corticosteroid therapy and the development of osteonecrosis was 179 days.

CONCLUSIONS: Post-COVID osteonecrosis appears to be more aggressive, with COVID-19 itself contributing to its etiopathogenesis in addition to corticosteroids. However, it can be diagnosed by magnetic resonance imaging (MRI) in symptomatic patients and then effectively treated medically, especially if detected in the early stages.

LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.}, } @article {pmid36420234, year = {2022}, author = {Sloop, GD and Pop, G and Weidman, JJ and St Cyr, JA}, title = {COVID-19 Demonstrates That Inflammation Is a Hyperviscous State.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e30603}, pmid = {36420234}, issn = {2168-8184}, abstract = {Many of the complications of severe coronavirus disease-2019 (COVID-19) are caused by blood hyperviscosity driven by marked hyperfibrinogenemia. This results in a distinctive hyperviscosity syndrome which affects areas of high and low shear. A change in blood viscosity causes a threefold inverse change in blood flow, which increases the risk of thrombosis in both arteries and veins despite prophylactic anticoagulation. Increased blood viscosity decreases perfusion of all tissues, including the lungs, heart, and brain. Decreased perfusion of the lungs causes global ventilation-perfusion mismatch which results in silent hypoxemia and decreased efficacy of positive pressure ventilation in treating pulmonary failure in COVID-19. Increased blood viscosity causes a mismatch in oxygen supply and demand in the heart, resulting in myocarditis and ventricular diastolic dysfunction. Decreased perfusion of the brain causes demyelination because of a sublethal cell injury to oligodendrocytes. Hyperviscosity can cause stasis in capillaries, which can cause endothelial necrosis. This can lead to the rarefaction of capillary beds, which is noted in "long-COVID." The genome of the virus which causes COVID-19, severe acute respiratory syndrome coronavirus 2, contains an extraordinarily high number of the oligonucleotide virulence factor 5'-purine-uridine-uridine-purine-uridine-3', which binds to toll-like receptor 8, hyperactivating innate immunity. This can lead to a marked elevation in fibrinogen levels and an increased prevalence of neutrophil extracellular traps in pulmonary failure, as seen in COVID-19 patients.}, } @article {pmid36417364, year = {2022}, author = {Pantelic, M and Ziauddeen, N and Boyes, M and O'Hara, ME and Hastie, C and Alwan, NA}, title = {Long Covid stigma: Estimating burden and validating scale in a UK-based sample.}, journal = {PloS one}, volume = {17}, number = {11}, pages = {e0277317}, pmid = {36417364}, issn = {1932-6203}, mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology ; RNA, Viral ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability. This study aimed to develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma.

METHODS: Data from the follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling was used. Thirteen questions on stigma were designed to develop the LCSS capturing three domains-enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated.

RESULTS: 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least 'sometimes' and 'often/always' was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without.

CONCLUSION: This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid.}, } @article {pmid36417318, year = {2023}, author = {Looi, JC and Maguire, PA and Kisely, SR and Allison, S}, title = {Psychiatrist and trainee moral injury during the organisational long COVID of Australian acute psychiatric inpatient services.}, journal = {Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists}, volume = {31}, number = {2}, pages = {121-123}, doi = {10.1177/10398562221142448}, pmid = {36417318}, issn = {1440-1665}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Inpatients ; *COVID-19 ; *Stress Disorders, Post-Traumatic ; Pandemics ; Australia/epidemiology ; SARS-CoV-2 ; *Psychiatry ; }, abstract = {OBJECTIVE: This paper provides a commentary on the risk of moral injury amongst psychiatrists and trainees working in the acute psychiatric hospital sector, during the third winter of the COVID-19 pandemic.

CONCLUSIONS: Moral injuries arise from observing, causing or failing to prevent adverse outcomes that transgress core ethical and moral values. Potentially, morally injurious events (PMIEs) are more prevalent and potent while demand on acute hospitals is heightened with the emergence of highly infectious SARS-CoV-2-Omicron subvariants (BA.4 and BA.5). Acute hospital inpatient services were already facing extraordinary stresses in the context of increasingly depleted infrastructure and staffing related to the pandemic. These stresses have a high potential to be morally injurious. It is essential to immediately fund additional staff and resources and address workplace health and safety, to seek to arrest a spiral of moral injury and burnout amongst psychiatrists and trainees. We discuss recommended support strategies.}, } @article {pmid36417267, year = {2022}, author = {Domènech-Montoliu, S and Puig-Barberà, J and Pac-Sa, MR and Vidal-Utrillas, P and Latorre-Poveda, M and Del Rio-González, A and Ferrando-Rubert, S and Ferrer-Abad, G and Sánchez-Urbano, M and Aparisi-Esteve, L and Badenes-Marques, G and Cervera-Ferrer, B and Clerig-Arnau, U and Dols-Bernad, C and Fontal-Carcel, M and Gomez-Lanas, L and Jovani-Sales, D and León-Domingo, MC and Llopico-Vilanova, MD and Moros-Blasco, M and Notari-Rodríguez, C and Ruíz-Puig, R and Valls-López, S and Arnedo-Pena, A}, title = {Complications Post-COVID-19 and Risk Factors among Patients after Six Months of a SARS-CoV-2 Infection: A Population-Based Prospective Cohort Study.}, journal = {Epidemiologia (Basel, Switzerland)}, volume = {3}, number = {1}, pages = {49-67}, pmid = {36417267}, issn = {2673-3986}, abstract = {In October 2020, we conducted a population-based prospective cohort study to determine post-COVID-19 complications, recovery, return to usual health, and associated risk factors in 536 cases of COVID-19 outbreak in Borriana (Spain) by administering an epidemiological questionnaire via phone interviews. A total of 484 patients participated (90.3%), age mean 37.2 ± 17.1 years, and 301 females (62.2%). Mild illness was the most common COVID-19 manifestation. After six months, 160 patients (33.1%) suffered at least one complication post-COVID-19, and 47 (29.4%) of them sought medical assistance. The most frequent persistent symptoms were hair loss, fatigue, loss of smell or taste, and headache. Risk factors associated with a complication were female sex (adjusted relative risk, [aRR] = 1.93 95% confidence interval [CI] 1.41-2.65), age 35 years and above (aRR = 1.50 95% CI 1.14-1.99), B blood group (aRR = 1.51 95% CI 1.04-2.16), current smoker (RR = 1.61 95% CI 1.02-2.54), and at least a COVID-19 exposure (aRR = 2.13 95% CI 1.11-4.09). Male sex, age younger than 35 years, and low COVID-19 exposures were associated with better recovery and return to usual health. A third of patients presented persistent symptoms compatible with the long-COVID-19 syndrome. In conclusion, an active medical follow-up of post-COVID-19 patients must be implemented.}, } @article {pmid36415469, year = {2022}, author = {Fritsche, LG and Jin, W and Admon, AJ and Mukherjee, B}, title = {Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36415469}, support = {K08 HL155407/HL/NHLBI NIH HHS/United States ; P30 CA046592/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: A growing number of Coronavirus Disease-2019 (COVID-19) survivors are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS). Using electronic health records data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models.

METHODS: In our cohort of 63,675 COVID-19 positive patients, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design and phenome-wide scans to characterize PASC-associated phenotypes of the pre-, acute-, and post-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance.

RESULTS: In the post-COVID-19 period, known PASC symptoms (e.g., shortness of breath, malaise/fatigue) and musculoskeletal, infectious, and digestive disorders were enriched among PASC cases. We found seven phenotypes in the pre-COVID-19 period (e.g., irritable bowel syndrome, concussion, nausea/vomiting) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological) associated with PASC. The derived pre- and acute-COVID-19 PheRSs stratified risk well, e.g., the combined PheRSs identified a quarter of the COVID-19 positive cohort with an at least 2.9-fold increased risk for PASC.

CONCLUSIONS: The uncovered PASC-associated diagnoses across categories highlighted a complex arrangement of presenting and likely predisposing features, some with a potential for risk stratification approaches.}, } @article {pmid36415464, year = {2022}, author = {Perlis, RH and Trujillo, KL and Safarpour, A and Santillana, M and Ognyanova, K and Druckman, J and Lazer, D}, title = {Research Letter: Association between long COVID symptoms and employment status.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36415464}, support = {R01 GM130668/GM/NIGMS NIH HHS/United States ; RF1 MH132335/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms.

METHOD: We analyzed a previously-reported cohort derived from 8 waves of a nonprobability-sample internet survey called the COVID States Project, conducted every 4-8 weeks between February 2021 and July 2022. Primary analyses examined associations between long COVID and lack of full employment or unemployment, adjusted for age, sex, race and ethnicity, education, urbanicity, and region, using multiple logistic regression with interlocking survey weights.

RESULTS: The cohort included 15,307 survey respondents ages 18-69 with test-confirmed COVID-19 at least 2 months prior, of whom 2,236 (14.6%) reported long COVID symptoms, including 1,027/2,236 (45.9%) reporting either 'brain fog' or impaired memory. Overall, 1,418/15,307 (9.3%) reported being unemployed, including 276/2,236 (12.3%) of those with long COVID and 1,142/13,071 (8.7%) of those without; 8,228 (53.8%) worked full-time, including 1,017 (45.5%) of those with long COVID and 7,211 (55.2%) without. In survey-weighted regression models, presence of long COVID was associated with being unemployed (crude OR 1.44, 95% CI 1.20-1.72; adjusted OR 1.23, 95% CI 1.02-1.48), and with lower likelihood of working full-time (crude OR 0.73, 95% CI 0.64-0.82; adjusted OR 0.79, 95% CI 0.70 -0.90). Among individuals with long COVID, the presence of cognitive symptoms - either brain fog or impaired memory - was associated with lower likelihood of working full time (crude OR 0.71, 95% CI 0.57-0.89, adjusted OR 0.77, 95% CI 0.61-0.97).

CONCLUSION: Long COVID was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. Presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to respond to long COVID, and particularly the associated neurocognitive symptoms.}, } @article {pmid36415203, year = {2022}, author = {Jiang, S and Loomba, J and Sharma, S and Brown, D and , and , }, title = {Vital Measurements of Hospitalized COVID-19 Patients as a Predictor of Long COVID: An EHR-based Cohort Study from the RECOVER Program in N3C.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {36415203}, issn = {2331-8422}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {It is shown that various symptoms could remain in the stage of post-acute sequelae of SARS-CoV-2 infection (PASC), otherwise known as Long COVID. A number of COVID patients suffer from heterogeneous symptoms, which severely impact recovery from the pandemic. While scientists are trying to give an unambiguous definition of Long COVID, efforts in prediction of Long COVID could play an important role in understanding the characteristic of this new disease. Vital measurements (e.g. oxygen saturation, heart rate, blood pressure) could reflect body's most basic functions and are measured regularly during hospitalization, so among patients diagnosed COVID positive and hospitalized, we analyze the vital measurements of first 7 days since the hospitalization start date to study the pattern of the vital measurements and predict Long COVID with the information from vital measurements.}, } @article {pmid36414624, year = {2022}, author = {Xiao, Y and Sharma, MM and Thiruvalluru, RK and Gimbrone, C and Weissman, MM and Olfson, M and Keyes, KM and Pathak, J}, title = {Trends in psychiatric diagnoses by COVID-19 infection and hospitalization among patients with and without recent clinical psychiatric diagnoses in New York city from March 2020 to August 2021.}, journal = {Translational psychiatry}, volume = {12}, number = {1}, pages = {492}, pmid = {36414624}, issn = {2158-3188}, support = {R01 MH121922/MH/NIMH NIH HHS/United States ; R01 MH119177/MH/NIMH NIH HHS/United States ; R25 MD011713/MD/NIMHD NIH HHS/United States ; R01 MH121907/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/epidemiology ; New York City/epidemiology ; SARS-CoV-2 ; Hospitalization ; Post-Acute COVID-19 Syndrome ; }, abstract = {Determining emerging trends of clinical psychiatric diagnoses among patients infected with the SARS-CoV-2 virus is important to understand post-acute sequelae of SARS-CoV-2 infection or long COVID. However, published reports accounting for pre-COVID psychiatric diagnoses have usually relied on self-report rather than clinical diagnoses. Using electronic health records (EHRs) among 2,358,318 patients from the New York City (NYC) metropolitan region, this time series study examined changes in clinical psychiatric diagnoses between March 2020 and August 2021 with month as the unit of analysis. We compared trends in patients with and without recent pre-COVID clinical psychiatric diagnoses noted in the EHRs up to 3 years before the first COVID-19 test. Patients with recent clinical psychiatric diagnoses, as compared to those without, had more subsequent anxiety disorders, mood disorders, and psychosis throughout the study period. Substance use disorders were greater between March and August 2020 among patients without any recent clinical psychiatric diagnoses than those with. COVID-19 positive patients (both hospitalized and non-hospitalized) had greater post-COVID psychiatric diagnoses than COVID-19 negative patients. Among patients with recent clinical psychiatric diagnoses, psychiatric diagnoses have decreased since January 2021, regardless of COVID-19 infection/hospitalization. However, among patients without recent clinical psychiatric diagnoses, new anxiety disorders, mood disorders, and psychosis diagnoses increased between February and August 2021 among all patients (COVID-19 positive and negative). The greatest increases were anxiety disorders (378.7%) and mood disorders (269.0%) among COVID-19 positive non-hospitalized patients. New clinical psychosis diagnoses increased by 242.5% among COVID-19 negative patients. This study is the first to delineate the impact of COVID-19 on different clinical psychiatric diagnoses by pre-COVID psychiatric diagnoses and COVID-19 infections and hospitalizations across NYC, one of the hardest-hit US cities in the early pandemic. Our findings suggest the need for tailoring treatment and policies to meet the needs of individuals with pre-COVID psychiatric diagnoses.}, } @article {pmid36414294, year = {2022}, author = {Elbéji, A and Zhang, L and Higa, E and Fischer, A and Despotovic, V and Nazarov, PV and Aguayo, G and Fagherazzi, G}, title = {Vocal biomarker predicts fatigue in people with COVID-19: results from the prospective Predi-COVID cohort study.}, journal = {BMJ open}, volume = {12}, number = {11}, pages = {e062463}, pmid = {36414294}, issn = {2044-6055}, mesh = {Humans ; Female ; Male ; Adult ; Middle Aged ; *COVID-19/diagnosis ; Prospective Studies ; Cohort Studies ; SARS-CoV-2 ; Biomarkers ; Fatigue/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To develop a vocal biomarker for fatigue monitoring in people with COVID-19.

DESIGN: Prospective cohort study.

SETTING: Predi-COVID data between May 2020 and May 2021.

PARTICIPANTS: A total of 1772 voice recordings were used to train an AI-based algorithm to predict fatigue, stratified by gender and smartphone's operating system (Android/iOS). The recordings were collected from 296 participants tracked for 2 weeks following SARS-CoV-2 infection.

Four machine learning algorithms (logistic regression, k-nearest neighbours, support vector machine and soft voting classifier) were used to train and derive the fatigue vocal biomarker. The models were evaluated based on the following metrics: area under the curve (AUC), accuracy, F1-score, precision and recall. The Brier score was also used to evaluate the models' calibrations.

RESULTS: The final study population included 56% of women and had a mean (±SD) age of 40 (±13) years. Women were more likely to report fatigue (p<0.001). We developed four models for Android female, Android male, iOS female and iOS male users with a weighted AUC of 86%, 82%, 79%, 85% and a mean Brier Score of 0.15, 0.12, 0.17, 0.12, respectively. The vocal biomarker derived from the prediction models successfully discriminated COVID-19 participants with and without fatigue.

CONCLUSIONS: This study demonstrates the feasibility of identifying and remotely monitoring fatigue thanks to voice. Vocal biomarkers, digitally integrated into telemedicine technologies, are expected to improve the monitoring of people with COVID-19 or Long-COVID.

TRIAL REGISTRATION NUMBER: NCT04380987.}, } @article {pmid36412591, year = {2022}, author = {Romeyke, T}, title = {A Multimodal Approach in the Treatment of Persistent Post-COVID.}, journal = {Diseases (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {36412591}, issn = {2079-9721}, abstract = {BACKGROUND: Many patients suffer from the consequences of a COVID infection. The so-called long or post-COVID syndrome affects the quality of life of patients and can lead to severe physical impairments. There are currently no suitable therapies for the treatment of long/post-COVID.

CASE PRESENTATION: A 49-year-old patient with post-COVID was admitted to a specialized clinic to carry out a multimodal therapy approach in the event of a therapy-resistant course. In addition to pronounced fatigue, sleep disorders, inner restlessness, and depression were seen in the patients' high levels of suffering. A naturopathic complex therapy including systemic whole-body hyperthermia was carried out. Well-being and physical well-being were recorded using the visual analog scale, and depression was recorded using the Patient Health Questionnaire Depression (PHQ-D). There was close monitoring of the vital parameters, and an evaluation of the therapy result was performed.

DISCUSSION AND CONCLUSION: The implementation of a naturopathic complex therapy including systemic whole-body hyperthermia was able to significantly improve the mental state, physical well-being, and mood of the patient. Since there are still no evidence-based therapy recommendations for the treatment of long/post-COVID, clinical research is called upon to intensively deal with this topic and to examine treatment concepts.}, } @article {pmid36412084, year = {2023}, author = {Astin, R and Banerjee, A and Baker, MR and Dani, M and Ford, E and Hull, JH and Lim, PB and McNarry, M and Morten, K and O'Sullivan, O and Pretorius, E and Raman, B and Soteropoulos, DS and Taquet, M and Hall, CN}, title = {Long COVID: mechanisms, risk factors and recovery.}, journal = {Experimental physiology}, volume = {108}, number = {1}, pages = {12-27}, pmid = {36412084}, issn = {1469-445X}, support = {RE/18/3/34214//British Heart Foundation/United Kingdom ; COV-LT2-0043//Department of Health/United Kingdom ; MR/V036750/1//Medical Research Council/United Kingdom ; NIHR200937//Department of Health/United Kingdom ; MR/S026495/1//Medical Research Council/United Kingdom ; MR/W004798/1//Medical Research Council/United Kingdom ; COV/LT2/0022//Department of Health/United Kingdom ; BRC-1215-20005//Department of Health/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Risk Factors ; *Autonomic Nervous System Diseases ; }, abstract = {NEW FINDINGS: What is the topic of this review? The emerging condition of long COVID, its epidemiology, pathophysiological impacts on patients of different backgrounds, physiological mechanisms emerging as explanations of the condition, and treatment strategies being trialled. The review leads from a Physiological Society online conference on this topic. What advances does it highlight? Progress in understanding the pathophysiology and cellular mechanisms underlying Long COVID and potential therapeutic and management strategies.

ABSTRACT: Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance - namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology - including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.}, } @article {pmid36412057, year = {2023}, author = {Takakura, K and Suka, M and Kajihara, M and Koido, S}, title = {Clinical features, therapeutic outcomes, and recovery period of long COVID.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28316}, pmid = {36412057}, issn = {1096-9071}, mesh = {Male ; Humans ; Female ; Adult ; *COVID-19/therapy ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Treatment Outcome ; Fatigue ; }, abstract = {To characterize the clinical features of long COVID, 286 patients who received care in our outpatient clinic for long COVID from May to December 2021 were surveyed. The recovery periods of each symptom and the key factors contributing to early recovery were statistically analysed. The median age of the patients was 35.8 years, with 137 men and 149 women. The median number of symptoms was 2.8. The most frequent symptoms were respiratory manifestations (52.1%), followed by fatigue (51.4%). Respiratory symptoms, fatigue, and headache/arthralgia were major complaints in the initial phase, whereas hair loss was a major complaint in the late phase, suggesting that the chief complaint of patients with long COVID may vary temporally. The best treatment outcome was observed for pulmonary symptoms, and hair loss had the worst outcome. COVID-19 severity, the number of manifestations, and the delay in starting treatment exerted a negative effect on the recovery period of long COVID. In addition, the smoking habit was an independent risk factor for slowing the recovery period from long COVID. This study provides insights into the clinical course of each manifestation and therapeutic options with a more certain future of long COVID to meet the unmet medical needs.}, } @article {pmid36410797, year = {2022}, author = {Corrado, J and Halpin, S and Preston, N and Whiteside, D and Tarrant, R and Davison, J and Simms, AD and O'Connor, RJ and Casson, A and Sivan, M}, title = {HEART rate variability biofeedback for long COVID symptoms (HEARTLOC): protocol for a feasibility study.}, journal = {BMJ open}, volume = {12}, number = {11}, pages = {e066044}, pmid = {36410797}, issn = {2044-6055}, support = {MC_PC_19042/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Humans ; Biofeedback, Psychology/methods ; *COVID-19 ; Dizziness ; Feasibility Studies ; Heart Rate/physiology ; Quality of Life ; RNA, Viral ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID (LC), also known as post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to one in seven people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the heart rate variability biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC.

METHODS AND ANALYSIS: 30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10 min periods everyday for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale, Composite Autonomic Symptom Score, WHO Disability Assessment Schedule and EQ-5D-5L health-related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data.

ETHICS AND DISSEMINATION: The study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications.

TRIAL REGISTRATION NUMBER: NCT05228665.}, } @article {pmid36408018, year = {2022}, author = {Líška, D and Liptaková, E and Babičová, A and Batalik, L and Baňárová, PS and Dobrodenková, S}, title = {What is the quality of life in patients with long COVID compared to a healthy control group?.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {975992}, pmid = {36408018}, issn = {2296-2565}, mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology ; Control Groups ; Cross-Sectional Studies ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Many patients have prolonged symptoms after COVID-19 infection, which can affect patient quality of life (QOL). The aim of this study is to determine the quality of life in patients with long COVID, compared with healthy controls.

MATERIAL AND METHODS: The study was a prospective cross-sectional study using an anonymous online survey. The SF-36 questionnaire was chosen for quality of life measurement. The survey was distributed through the Facebook social media platform targeting groups of patients with long COVID. The control group was made up of physiotherapy and physical education students.

RESULTS: There was a significant difference in physical function, with a mean score of 94.9 (±9.4) among the students, compared to long COVID patients with a mean score of 66.2 (±25.4) (p < 0.001). A similar result was found in the physical role (p < 0.001). The overall quality of life score for college students was 578.0 (±111.9), and the overall score for patients with long COVID was 331.9 (±126.9).

CONCLUSIONS: Patients with long COVID had a lower quality of life compared to the healthy control group, and this was associated with the negative effect of long-COVID. Lower quality of life in patients with long COVID is an important therapeutic goal, which requires attention.}, } @article {pmid36407988, year = {2022}, author = {Aghaei, A and Aggarwal, A and Zhang, R and Li, X and Qiao, S}, title = {Resilience resources and coping strategies of COVID-19 female long haulers: A qualitative study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {970378}, pmid = {36407988}, issn = {2296-2565}, support = {R01 AI127203/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19 ; Adaptation, Psychological ; Qualitative Research ; Social Support ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Female long haulers deal with persistent post-acute COVID-19 symptoms that have serious health implications. This study aimed to identify resilience resources at multiple socio-ecological levels for female long haulers and describe how resilience resources affect their responses to long COVID.

METHODS: Purposive sampling was adopted to recruit participants through social media from April to June 2021 followed by 15 semi-structured interviews. An inductive analytical approach was adopted to categorize themes by open and axial coding that were verified by peer review.

RESULTS: Female long haulers relied on resources at various socio-ecological levels to foster their resilience in response to long COVID. At the individual level, they utilized cognitive and emotional resources to increase knowledge, learn new skills, set goals, and manage emotions; behavioral resources (e.g., internal motivation and executive functioning) to perform physical, creative, and recreational activities, and adopt healthier eating habits; and spiritual resources to perform spiritual rituals and connect with God. At the social level, the support from existing relationships and/or online social support groups enhanced their social identity and provided material and informational resources. At the health systems level, the guidance from counselors and physicians and availability of clinics, medicines, and health equipment assisted them in symptom management and medication adherence.

CONCLUSION: The resilience of female long haulers can be enhanced through (1) offering financial and health-related resources, (2) developing online social-support groups, (3) counseling and care service training for healthcare professionals, and (4) implementing more psychosocial interventions by labor organizations.}, } @article {pmid36407125, year = {2023}, author = {Buonsenso, D}, title = {Pharmacological trials for long COVID: first light at the end of the tunnel.}, journal = {The Lancet regional health. Europe}, volume = {24}, number = {}, pages = {100544}, pmid = {36407125}, issn = {2666-7762}, } @article {pmid36407052, year = {2022}, author = {Banerjee, I and Robinson, J and Sathian, B}, title = {Treatment of Long COVID or Post COVID syndrome: A Pharmacological approach.}, journal = {Nepal journal of epidemiology}, volume = {12}, number = {3}, pages = {1220-1223}, pmid = {36407052}, issn = {2091-0800}, } @article {pmid36406042, year = {2022}, author = {van Elst, JM and Boesveldt, S and Vissink, A and Jager-Wittenaar, H and Reyners, AKL and de Haan, JJ}, title = {Subjective Mouthfeel and Temperature Alterations in COVID-19 Patients Six to Ten Months After Diagnosis.}, journal = {Chemosensory perception}, volume = {15}, number = {2}, pages = {165-174}, pmid = {36406042}, issn = {1936-5802}, abstract = {INTRODUCTION: The characteristics and impact of mouthfeel, temperature, smell, and taste alterations in patients with COVID-19 at a long term are yet not well known. In this study, these characteristics and their impact on daily life and quality of life (QoL) were assessed, six to ten months after infection, in patients with COVID-19 searching for peer support on Facebook.

METHODS: Between December 2020 and January 2021, members of two COVID-19 Facebook groups were invited to complete a questionnaire. Participants were asked to report their perception of mouthfeel, temperature, smell, and taste alterations and their impact.

RESULTS: The questionnaire was completed by 157/216 respondents (73%), with 92% being women. Alterations in mouthfeel, temperature, smell, and taste were reported by respectively 66, 40, 148, and 133 participants. The most frequently reported mouthfeel alterations were "a different feeling" and "dry mouth" in 38 and 30 participants, respectively. Preferences for food temperature were equally changed to "freezing", "cool", "room temperature", "a bit warmer", and "warmer". An impact on daily life and QoL was reported by most patients with alterations in mouthfeel (91% and 79%), temperature (78% and 60%), smell (98% and 93%), and taste (93% and 88%), respectively.

CONCLUSIONS: Patients with COVID-19 searching for peer support on Facebook experienced, next to smell and taste alterations, mouthfeel and temperature disturbances, six to ten months after infection. These alterations have an impact on daily life and QoL.

IMPLICATIONS: Health professionals should, next to smell and taste alterations, be aware of mouthfeel and temperature alterations in patients with COVID-19.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12078-022-09304-y.}, } @article {pmid36405695, year = {2022}, author = {Zhao, J and Zhu, J and Huang, C and Zhu, X and Zhu, Z and Wu, Q and Yuan, R}, title = {Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1035151}, pmid = {36405695}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Periodicals as Topic ; Bibliometrics ; }, abstract = {BACKGROUND: Since the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics.

METHODS: Publications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis.

RESULTS: 1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: "Delta/Omicron variants", "cytokine storm", "neutralization/neutralizing antibody", "T cell", "BNT162b2", "mRNA vaccine", "vaccine effectiveness/safety", and "long COVID".

CONCLUSION: This study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.}, } @article {pmid36405232, year = {2022}, author = {Sakellaropoulos, SG and Ali, M and Papadis, A and Mohammed, M and Mitsis, A and Zivzivadze, Z}, title = {Is Long COVID Syndrome a Transient Mitochondriopathy Newly Discovered: Implications of CPET.}, journal = {Cardiology research}, volume = {13}, number = {5}, pages = {264-267}, pmid = {36405232}, issn = {1923-2829}, abstract = {The new outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has an impact worldwide, primarily as a medical emergency. Even that the total constellation is considered as a pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19) gives rise to dysfunction in multiple organs (e.g., brain, lungs, heart, muscles) that impairs cardiopulmonary (CP) function. Parallel to the CP consequences of COVID-19 is a significant reduction in physical activity. Cardiopulmonary exercise testing (CPET) is daily used in clinical practice to define prognosis, provide risk stratification and treatment strategy. As such, the significance of CPET is crucial concerning clinical assessments of COVID-19 patients. Furthermore, new studies aim at understanding the effects of SARS-CoV-2 infection in long term. Multiple studies have investigated the cardiopulmonary function and impairment of exercise endurance in such patients, as well as a possible prolonged physical impairment. With this review, we summarize the COVID-19-associated pathophysiology for the Long COVID (LC) syndrome as well as the importance of performing CPET.}, } @article {pmid36404774, year = {2024}, author = {Nouraeinejad, A}, title = {The pathological mechanisms underlying brain fog or cognitive impairment in long COVID.}, journal = {The International journal of neuroscience}, volume = {134}, number = {7}, pages = {812-813}, doi = {10.1080/00207454.2022.2150845}, pmid = {36404774}, issn = {1563-5279}, mesh = {Humans ; *COVID-19/complications ; *Cognitive Dysfunction/etiology/physiopathology ; Brain/physiopathology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36403699, year = {2023}, author = {Rombauts, A and Infante, C and de Lagos, MDÁM and Alba, J and Valiente, A and Donado-Mazarrón, C and Carretero-Ledesma, M and Rodríguez-Álvarez, R and Omatos, S and Palacios-Baena, ZR and Abelenda-Alonso, G and Silva-Sánchez, MDM and Goikoetxea-Agirre, AJ and Oteo, JA and Rodríguez-Baño, J and Cordero, E and Gudiol, C and Sánchez-Céspedes, J and Carratalà, J}, title = {Impact of SARS-CoV-2 RNAemia and other risk factors on long-COVID: A prospective observational multicentre cohort study.}, journal = {The Journal of infection}, volume = {86}, number = {2}, pages = {154-225}, pmid = {36403699}, issn = {1532-2742}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Risk Factors ; Cohort Studies ; RNA, Viral/genetics ; }, } @article {pmid36403360, year = {2022}, author = {Gasnier, M and Montani, D and Corruble, E and Colle, R and , }, title = {Psychiatric disorders and long COVID.}, journal = {Respiratory medicine and research}, volume = {82}, number = {}, pages = {100958}, pmid = {36403360}, issn = {2590-0412}, mesh = {Humans ; *COVID-19/psychology ; *Mental Disorders/diagnosis/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36400555, year = {2023}, author = {Hovaguimian, A}, title = {Dysautonomia: Diagnosis and Management.}, journal = {Neurologic clinics}, volume = {41}, number = {1}, pages = {193-213}, doi = {10.1016/j.ncl.2022.08.002}, pmid = {36400555}, issn = {1557-9875}, mesh = {Humans ; *COVID-19 ; *Primary Dysautonomias/diagnosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Dysautonomias are a heterogenous group of disorders that can cause variable symptoms ranging from isolated impairment of one autonomic function to multisystem failure. The causes are also diverse and can be central or peripheral and primary (owing to an intrinsic neurologic cause) or secondary (owing to a disorder that secondarily causes damage to the autonomic nervous system). This review covers common phenotypes of dysautonomias, primary and secondary causes, initial clinical workups, interpretation of common autonomic tests, and first-line treatments. A brief review of autonomic impairment associated with acute and long-COVID is also presented.}, } @article {pmid36398720, year = {2023}, author = {Scarpelli, S and De Santis, A and Alfonsi, V and Gorgoni, M and Morin, CM and Espie, C and Merikanto, I and Chung, F and Penzel, T and Bjorvatn, B and Dauvilliers, Y and Holzinger, B and Wing, YK and Partinen, M and Plazzi, G and De Gennaro, L}, title = {The role of sleep and dreams in long-COVID.}, journal = {Journal of sleep research}, volume = {32}, number = {3}, pages = {e13789}, doi = {10.1111/jsr.13789}, pmid = {36398720}, issn = {1365-2869}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; RNA, Viral ; *COVID-19 ; SARS-CoV-2 ; Sleep ; }, abstract = {Recent investigations show that many people affected by SARS-CoV2 (COVID-19) report persistent symptoms 2-3 months from the onset of the infection. Here, we report the Italian findings from the second International COVID-19 Sleep Study survey, aiming to investigate sleep and dream alterations in participants with post-acute symptoms, and identify the best determinants of these alterations among patients with long-COVID. Data from 383 participants who have had COVID-19 were collected through a web-survey (May-November 2021). Descriptive analyses were performed to outline the sociodemographic characteristics of long-COVID (N = 270, with at least two long-lasting symptoms) and short-COVID (N = 113, with none or one long-lasting symptom) participants. They were then compared concerning sleep and dream measures. We performed multiple linear regressions considering as dependent variables sleep and dream parameters discriminating the long-COVID group. Age, gender, work status, financial burden, COVID-19 severity and the level of care were significantly different between long-COVID and short-COVID subjects. The long-COVID group showed greater sleep alterations (sleep quality, daytime sleepiness, sleep inertia, naps, insomnia, sleep apnea, nightmares) compared with the short-COVID group. We also found that the number of long-COVID symptoms, psychological factors and age were the best explanatory variables of sleep and oneiric alterations. Our findings highlight that sleep alterations are part of the clinical presentation of the long-COVID syndrome. Moreover, psychological status and the number of post-acute symptoms should be considered as state-like variables modulating the sleep problems in long-COVID individuals. Finally, according to previous investigations, oneiric alterations are confirmed as a reliable mental health index.}, } @article {pmid36396269, year = {2022}, author = {Dix, E and Roy, K}, title = {COVID-19: Brain Effects.}, journal = {The Psychiatric clinics of North America}, volume = {45}, number = {4}, pages = {625-637}, pmid = {36396269}, issn = {1558-3147}, mesh = {Humans ; Aged ; *COVID-19 ; Brain/pathology ; Aging ; }, abstract = {Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for the coronavirus disease (COVID-19), affects the brain. Neurologic and neuropsychiatric symptoms may manifest in the acute and post-acute phases of illness. The vulnerability of the brain with aging further increases the burden of disease in the elderly, who are at the highest risk of complications and death from COVID-19. The mechanisms underlying the effects of COVID-19 on the brain are not fully known. Emerging evidence vis-à-vis pathogenesis and etiologies of COVID-19 brain effects is promising and may pave the way for future research and development of interventions.}, } @article {pmid36389819, year = {2022}, author = {Tian, J and Dillion, BJ and Henley, J and Comai, L and Kaufman, DL}, title = {A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1007955}, pmid = {36389819}, issn = {1664-3224}, support = {UL1 TR001881/TR/NCATS NIH HHS/United States ; }, mesh = {Mice ; Humans ; Animals ; SARS-CoV-2 ; Viral Load ; *Pneumonia ; gamma-Aminobutyric Acid ; *COVID-19 Drug Treatment ; }, abstract = {Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). Because MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, we sought to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection. We observed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice. GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19. The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials. We also discuss the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation.}, } @article {pmid36389746, year = {2022}, author = {Giménez-Orenga, K and Pierquin, J and Brunel, J and Charvet, B and Martín-Martínez, E and Perron, H and Oltra, E}, title = {HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1020064}, pmid = {36389746}, issn = {1664-3224}, mesh = {Humans ; *Endogenous Retroviruses ; *COVID-19 ; SARS-CoV-2 ; *Multiple Sclerosis ; Immunoglobulin E ; }, abstract = {Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other. The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01). These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.}, } @article {pmid36388207, year = {2022}, author = {Cheshire, WP}, title = {The grand challenge of autonomic disorders.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1052137}, pmid = {36388207}, issn = {1664-2295}, } @article {pmid36387947, year = {2022}, author = {Porter, N and Jason, LA}, title = {Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2599-2626}, pmid = {36387947}, issn = {1176-6328}, abstract = {Some individuals infected with SARS CoV-2 have developed Post-Acute Sequelae of SARS CoV-2 infection (PASC) or what has been referred to as Long COVID. Efforts are underway to find effective treatment strategies for those with Long COVID. One possible approach involves alternative medical interventions, which have been widely used to treat and manage symptoms of a variety of medical problems including post-viral infections. Meditation has been found to reduce fatigue and unrefreshing sleep, and for those with post-viral infections, it has enhanced immunity, and reduced inflammatory-driven pathogenesis. Our article summarizes the literature on what is known about mindfulness meditation interventions, and reviews evidence on how it may apply to those with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Evidence is reviewed suggesting effective and sustainable outcomes may be achieved for symptomatology and underlying pathology of post-viral fatigue (PASC and ME/CFS).}, } @article {pmid36386945, year = {2022}, author = {Gaylis, NB and Kreychman, I and Sagliani, J and Mograbi, J and Gabet, Y}, title = {The results of a unique dietary supplement (nutraceutical formulation) used to treat the symptoms of long-haul COVID.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1034169}, pmid = {36386945}, issn = {2296-861X}, abstract = {Long-COVID is a syndrome characterized by debilitating symptoms that persist over 3 months after infection with the SARS-CoV-2 virus. It affects 15 to 33% of COVID-19 recovered patients and has no dedicated treatment. First, we found that β-caryophyllene and pregnenolone have a significant synergistic effect in the resolution of LPS-induced sepsis and inflammation in mice. Then we combined these two compounds with seven others and designed a unique dietary supplement formulation to alleviate long COVID inflammatory and neurological disorders. We performed a one-arm open-labeled study at a single site with 51 eligible patients from 18 states. Each participant recorded the severity level of 12 symptoms (including fatigue, weakness, cardiac and neurological symptoms, shortness of breath, gastrointestinal disorders, ageusia or anosmia, anxiety, joint pain, rash, cough, and insomnia) at baseline, 2- and 4-week time points. On average, all the symptoms were significantly milder after 2 weeks, with further improvement after 4 weeks. Importantly, each symptom was significantly attenuated in 72 to 84% of the participants. There were no significant adverse effects. Our data indicate that the use of this nutraceutical product is a safe and significantly efficient option to reduce multiple symptoms of long COVID.}, } @article {pmid36385522, year = {2023}, author = {Wright, FL and Cheema, K and Goldacre, R and Hall, N and Herz, N and Islam, N and Karim, Z and Moreno-Martos, D and Morales, DR and O'Connell, D and Spata, E and Akbari, A and Ashworth, M and Barber, M and Briffa, N and Canoy, D and Denaxas, S and Khunti, K and Kurdi, A and Mamas, M and Priedon, R and Sudlow, C and Morris, EJA and Lacey, B and Banerjee, A}, title = {Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.}, journal = {European heart journal. Quality of care & clinical outcomes}, volume = {9}, number = {4}, pages = {377-388}, pmid = {36385522}, issn = {2058-1742}, support = {MR/V028367/1/MRC_/Medical Research Council/United Kingdom ; MR/K006584/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; SP/19/3/34 678/BHF_/British Heart Foundation/United Kingdom ; MR/V028367/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; /CSO_/Chief Scientist Office/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; *Cardiovascular Diseases/epidemiology/therapy ; Pandemics ; Secondary Care ; Electronic Health Records ; *Venous Thromboembolism ; England/epidemiology ; *Stroke/epidemiology ; *Heart Failure ; }, abstract = {BACKGROUND: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described.

METHODS AND RESULTS: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions.

CONCLUSION: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.}, } @article {pmid36385449, year = {2023}, author = {Kubota, T and Kuroda, N and Sone, D}, title = {Neuropsychiatric aspects of long COVID: A comprehensive review.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {2}, pages = {84-93}, pmid = {36385449}, issn = {1440-1819}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Anxiety Disorders ; }, abstract = {Although some patients have persistent symptoms or develop new symptoms following coronavirus disease 2019 (COVID-19) infection, neuropsychiatric aspects of long COVID are not well known. This review summarizes and provides an update on the neuropsychiatric dimensions of long COVID. Its neuropsychiatric manifestations commonly include fatigue, cognitive impairment, sleep disorders, depression, anxiety, and post-traumatic stress disorder. There are no specific tests for long COVID, but some characteristic findings such as hypometabolism on positron emission tomography have been reported. The possible mechanisms of long COVID include inflammation, ischemic effects, direct viral invasion, and social and environmental changes. Some patient characteristics and the severity and complications of acute COVID-19 infection may be associated with an increased risk of neuropsychiatric symptoms. Long COVID may resolve spontaneously or persist, depending on the type of neuropsychiatric symptoms. Although established treatments are lacking, various psychological and pharmacological treatments have been attempted. Vaccination against COVID-19 infection plays a key role in the prevention of long coronavirus disease. With differences among the SARS-CoV-2 variants, including the omicron variant, the aspects of long COVID are likely to change in the future. Further studies clarifying the aspects of long COVID to develop effective treatments are warranted.}, } @article {pmid36385229, year = {2022}, author = {Wagner, C and Griesel, M and Mikolajewska, A and Metzendorf, MI and Fischer, AL and Stegemann, M and Spagl, M and Nair, AA and Daniel, J and Fichtner, F and Skoetz, N}, title = {Systemic corticosteroids for the treatment of COVID-19: Equity-related analyses and update on evidence.}, journal = {The Cochrane database of systematic reviews}, volume = {11}, number = {11}, pages = {CD014963}, pmid = {36385229}, issn = {1469-493X}, mesh = {Humans ; Aged ; Aged, 80 and over ; Adrenal Cortex Hormones/adverse effects ; Methylprednisolone ; Dexamethasone/adverse effects ; *Invasive Fungal Infections ; Randomized Controlled Trials as Topic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.

OBJECTIVES: To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach.

SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections.

MAIN RESULTS: We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; ≥ 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease.

AUTHORS' CONCLUSIONS: Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.}, } @article {pmid36384641, year = {2022}, author = {Deforth, M and Gebhard, CE and Bengs, S and Buehler, PK and Schuepbach, RA and Zinkernagel, AS and Brugger, SD and Acevedo, CT and Patriki, D and Wiggli, B and Twerenbold, R and Kuster, GM and Pargger, H and Schefold, JC and Spinetti, T and Wendel-Garcia, PD and Hofmaenner, DA and Gysi, B and Siegemund, M and Heinze, G and Regitz-Zagrosek, V and Gebhard, C and Held, U}, title = {Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms.}, journal = {Diagnostic and prognostic research}, volume = {6}, number = {1}, pages = {22}, pmid = {36384641}, issn = {2397-7523}, support = {Grant number//The Loop Zurich/ ; 196140//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19.

METHODS: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance.

RESULTS: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09).

CONCLUSION: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended.}, } @article {pmid36382632, year = {2022}, author = {Ambrosino, P and Sanduzzi Zamparelli, S and Mosella, M and Formisano, R and Molino, A and Spedicato, GA and Papa, A and Motta, A and Di Minno, MND and Maniscalco, M}, title = {Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions.}, journal = {Annals of medicine}, volume = {54}, number = {1}, pages = {3234-3249}, pmid = {36382632}, issn = {1365-2060}, mesh = {Humans ; *COVID-19 ; Endothelium ; }, abstract = {BACKGROUND: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19.

METHODS: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684.

RESULTS: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p < 0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p = 0.037).

CONCLUSIONS: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.}, } @article {pmid36381920, year = {2022}, author = {Kingma, TJ and Hoch, V and Johnson, C and Chaudhry, B}, title = {Avascular Necrosis of the Hip: A Post COVID-19 Sequela.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e29976}, pmid = {36381920}, issn = {2168-8184}, abstract = {A 60-year-old African American male presented to the hospital with seven months of progressively worsening left anterior hip pain with no known trauma. Two months after the pain onset, he underwent an x-ray of the pelvis with the lateral left hip, revealing dystrophic soft tissue calcification adjacent to the superolateral left acetabulum. Pain at this time was attributed to presumed sciatica vs arthritis. The patient underwent multimodal treatment for his pain without relief. In the month prior to the presentation, the patient also developed right hip pain. He then underwent a bilateral hip x-ray, revealing left femoral neck lucency suspicious for a nondisplaced fracture. CT pelvis was ordered at this time for further evaluation and demonstrated bilateral subcapital hip fractures. He was subsequently discharged from the emergency department with pending laboratory work and plans for close outpatient orthopedic surgery follow-up. The following day, the patient was instructed to return to the hospital due to an elevated erythrocyte sedimentation rate of 39 mm/hr and C-reactive protein of 41.6 mg/L. Subsequent MRI pelvis revealed bilateral subcapital femoral neck fractures with avascular necrosis (AVN) requiring surgical intervention with bilateral hip arthroplasty. Our patient underwent an extensive workup with no evidence of traditional risk factors for osteonecrosis, osteopenia, or other bone diseases. A pertinent finding in the patient's history was an admission for severe SARS-CoV-2 (COVID-19) infection 10 months prior. 'Long COVID' is a complex illness that has been shown to affect intravascular blood flow, and likely contributed to the development of bilateral hip AVN in our patient. Given this novel presentation, it is crucial that AVN be considered early in evaluating anterior hip pain for patients with a history of COVID-19 infection in order to avoid severe consequences such as femoral neck fractures.}, } @article {pmid36379498, year = {2022}, author = {}, title = {Long COVID: What You Should Know.}, journal = {American family physician}, volume = {106}, number = {5}, pages = {Online}, pmid = {36379498}, issn = {1532-0650}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36379497, year = {2022}, author = {Herman, E and Shih, E and Cheng, A}, title = {Long COVID: Rapid Evidence Review.}, journal = {American family physician}, volume = {106}, number = {5}, pages = {523-532}, pmid = {36379497}, issn = {1532-0650}, mesh = {United States ; Humans ; *COVID-19/diagnosis/therapy ; Headache/etiology ; Chest Pain ; Fatigue/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Postacute sequelae of COVID-19, also known as long COVID, affects approximately 10% to 30% of the hundreds of millions of people who have had acute COVID-19. The Centers for Disease Control and Prevention defines long COVID as the presence of new, returning, or ongoing symptoms associated with acute COVID-19 that persist beyond 28 days. The diagnosis of long COVID can be based on a previous clinical diagnosis of COVID-19 and does not require a prior positive polymerase chain reaction or antigen test result to confirm infection. Patients with long COVID report a broad range of symptoms, including abdominal pain, anosmia, chest pain, cognitive impairment (brain fog), dizziness, dyspnea, fatigue, headache, insomnia, mood changes, palpitations, paresthesias, and postexertional malaise. The presentation is variable, and symptoms can fluctuate or persist and relapse and remit. The diagnostic approach is to differentiate long COVID from acute sequelae of COVID-19, previous comorbidities, unmasking of preexisting health conditions, reinfections, new acute concerns, and complications of prolonged illness, hospitalization, or isolation. Many presenting symptoms of long COVID are commonly seen in a primary care practice, and management can be improved by using established treatment paradigms and supportive care. Although several medications have been suggested for the treatment of fatigue related to long COVID, the evidence for their use is currently lacking. Holistic treatment strategies for long COVID include discussion of pacing and energy conservation; individualized, symptom-guided, phased return to activity programs; maintaining adequate hydration and a healthy diet; and treatment of underlying medical conditions.}, } @article {pmid36379490, year = {2022}, author = {Wadhwa, A}, title = {Long COVID in Children: What Do We Know?.}, journal = {American family physician}, volume = {106}, number = {5}, pages = {488-489}, pmid = {36379490}, issn = {1532-0650}, mesh = {Child ; Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36379135, year = {2022}, author = {Frontera, JA and Sabadia, S and Yang, D and de Havenon, A and Yaghi, S and Lewis, A and Lord, AS and Melmed, K and Thawani, S and Balcer, LJ and Wisniewski, T and Galetta, SL and , }, title = {Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization.}, journal = {Journal of the neurological sciences}, volume = {443}, number = {}, pages = {120487}, pmid = {36379135}, issn = {1878-5883}, support = {U24 NS113844/NS/NINDS NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; R01 AG077422/AG/NIA NIH HHS/United States ; P01 AG060882/AG/NIA NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19 ; Activities of Daily Living ; Prospective Studies ; Quality of Life/psychology ; Longitudinal Studies ; Hospitalization ; Fatigue/epidemiology/etiology ; }, abstract = {BACKGROUND: Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19.

METHODS: We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression.

RESULTS: Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms).

CONCLUSIONS: Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.}, } @article {pmid36378504, year = {2022}, author = {Fischer, A and Elbeji, A and Aguayo, G and Fagherazzi, G}, title = {Recommendations for Successful Implementation of the Use of Vocal Biomarkers for Remote Monitoring of COVID-19 and Long COVID in Clinical Practice and Research.}, journal = {Interactive journal of medical research}, volume = {11}, number = {2}, pages = {e40655}, pmid = {36378504}, issn = {1929-073X}, abstract = {The COVID-19 pandemic accelerated the use of remote patient monitoring in clinical practice or research for safety and emergency reasons, justifying the need for innovative digital health solutions to monitor key parameters or symptoms related to COVID-19 or Long COVID. The use of voice-based technologies, and in particular vocal biomarkers, is a promising approach, voice being a rich, easy-to-collect medium with numerous potential applications for health care, from diagnosis to monitoring. In this viewpoint, we provide an overview of the potential benefits and limitations of using voice to monitor COVID-19, Long COVID, and related symptoms. We then describe an optimal pipeline to bring a vocal biomarker candidate from research to clinical practice and discuss recommendations to achieve such a clinical implementation successfully.}, } @article {pmid36378091, year = {2023}, author = {Ross, SM}, title = {Long COVID and Mitochondrial Dysfunction.}, journal = {Holistic nursing practice}, volume = {37}, number = {1}, pages = {51-53}, doi = {10.1097/HNP.0000000000000566}, pmid = {36378091}, issn = {1550-5138}, mesh = {Humans ; *COVID-19 ; Mitochondria ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36376776, year = {2022}, author = {d'Ettorre, G and Vassalini, P and Coppolelli, V and Gentilini Cacciola, E and Sanitinelli, L and Maddaloni, L and Fabris, S and Mastroianni, CM and d'Ettorre, G and Ceccarelli, G}, title = {Health-related quality of life in survivors of severe COVID-19 infection.}, journal = {Pharmacological reports : PR}, volume = {74}, number = {6}, pages = {1286-1295}, pmid = {36376776}, issn = {2299-5684}, mesh = {Humans ; Female ; *Quality of Life ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Long-term effects of Coronavirus Disease 2019 (COVID-19) are increasingly recognized as having a significant impact on Health-Related Quality of Life (HRQoL). Understanding HRQoL status for each patient affected by long COVID-19 and its determinants may have a key role to prevent and treat this condition.

METHODS: In this prospective observational study conducted in a large academic COVID-19 hospital in Rome, participants were contacted 2 years after hospital admission for severe COVID-19. To assess HRQoL, EQ-5D-5L and Visual analog scale (EQ VAS) standard questionnaires were administered by interview. Logistic regression model was used to the five health dimensions as dependent variables (0 = no problem, 1 = some/extreme problem).

KEY RESULTS: In 137 enrolled patients, the mean pre-COVID and post-COVID EQ-5D-5L index and EQ-VAS score were 0.97 (SD 0.06), 0.79 (SD 0.26) and 72.38 (SD 15.18), respectively. After subdivision of the participants for clinical and social variables, the EQ-5D-5L index resulted significantly lower than in the pre-COVID-19 period. Female gender, unemployed status, and chronic comorbidities were the most common predictors for having any problems in each EQ-5D-5L domain, while also older age and higher Body Mass Index (BMI) showed to be related to a lower EQ-VAS score.

CONCLUSION: HRQoL showed to be still low in patients 2 years after acute severe COVID-19. Given the significant impact of SARS-CoV-2 on long-term chronic symptoms, predictors of poor outcomes must be considered during the acute phase of illness to plan a tailored follow-up path for each patient.}, } @article {pmid36375693, year = {2023}, author = {Brunvoll, SH and Nygaard, AB and Fagerland, MW and Holland, P and Ellingjord-Dale, M and Dahl, JA and Søraas, A}, title = {Post-acute symptoms 3-15 months after COVID-19 among unvaccinated and vaccinated individuals with a breakthrough infection.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {126}, number = {}, pages = {10-13}, pmid = {36375693}, issn = {1878-3511}, mesh = {Humans ; *COVID-19/diagnosis ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; Vaccination ; }, abstract = {OBJECTIVE: We aimed to describe post-acute sequelae of SARS-CoV-2 infection (PASC) related symptoms 3-15 months after a positive test in SARS-CoV-2 unvaccinated and vaccinated participants with a breakthrough infection.

METHODS: Participants of the Norwegian COVID-19 cohort, without a positive SARS-CoV-2 test, completed a questionnaire about PASC-related symptoms between November 2020 and January 2021. About a year later, a second questionnaire (which also included the Everyday Memory Questionnaire [EMQ]-13) was completed by the same participants, most still without a positive SARS-CoV-2 test, but also by unvaccinated and vaccinated participants with a positive test 3-15 months before the questionnaire. Laboratory-confirmed SARS-CoV-2 status (positive or negative swab test determined by reverse transcriptase quantitative polymerase chain reaction) at the time of completing the questionnaire was ascertained from the Mandatory Norwegian Surveillance System for Communicable Diseases.

RESULTS: No differences were found in the self-reported PASC symptoms, dyspnea, fatigue, smell/taste changes, concentration problems, or the EMQ-13 score between unvaccinated and vaccinated participants 3-15 months after the positive test. Fewer memory problems were reported among vaccinated than unvaccinated participants.

CONCLUSION: SARS-CoV-2 vaccines offer minor protection against PASC symptoms, although fewer memory problems were reported among the vaccinated than the unvaccinated participants.}, } @article {pmid36373223, year = {2023}, author = {Bernas, SN and Baldauf, H and Real, R and Sauter, J and Markert, J and Trost, S and Tausche, K and Behrends, U and Schmidt, AH and Schetelig, J}, title = {Post-COVID-19 condition in the German working population: A cross-sectional study of 200,000 registered stem cell donors.}, journal = {Journal of internal medicine}, volume = {293}, number = {3}, pages = {354-370}, pmid = {36373223}, issn = {1365-2796}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; *COVID-19/epidemiology ; SARS-CoV-2 ; Cross-Sectional Studies ; Risk Factors ; Stem Cells ; }, abstract = {BACKGROUND: The SARS-CoV-2 pandemic has strained health systems worldwide, and infection numbers continue to rise. While previous data have already shown that many patients suffer from symptoms for months after an acute infection, data on risk factors and long-term outcomes are incomplete, particularly for the working population.

OBJECTIVES: We aimed to provide information on the prevalence of post-COVID-19 conditions in a subset of the German working-age population (18-61 years old) and to analyze risk factors.

METHODS: We conducted an online survey with a health questionnaire among registered potential stem cell donors with or without a self-reported history of polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Logistic regression models were used to examine the risks of severity of acute infection, sex, age, body mass index, diabetes mellitus, and arterial hypertension medication on post-COVID-19 symptoms.

RESULTS: A total of 199,377 donors reported evaluable survey questionnaires-12,609 cases had a history of SARS-CoV-2 infection and 186,768 controls had none. Overall, cases reported physical, cognitive, and psychological complaints more frequently compared to controls. Increased rates of complaints persisted throughout 15 months postinfection, for example, 28.4%/19.3% of cases/controls reported fatigue (p <0.0001) and 9.5%/3.6% of cases/controls reported loss of concentration (p <0.0001). No significant differences were observed in the frequency of reported symptoms between 3 and 15 months postinfection. Multivariate analysis revealed a strong influence of the severity of the acute SARS-CoV-2 infection episode and age on the risk for post-COVID-19 conditions.

CONCLUSION: We report the prevalence of post-COVID-19 conditions in mainly unvaccinated individuals with SARS-CoV-2 infections between February 2020 and August 2021. The severity of the acute course and age were major risk factors. Vaccinations may reduce the risk of post-COVID-19 conditions by reducing the risk of severe infections.}, } @article {pmid36369815, year = {2022}, author = {Barbara, JM and Gatt, J and Xuereb, RA and Tabone Adami, N and Darmanin, J and Erasmi, R and G Xuereb, R and Barbara, C and Stephen, F and Jane Magri, C}, title = {Clinical outcomes at medium-term follow-up of COVID-19.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {52}, number = {3}, pages = {220-227}, pmid = {36369815}, issn = {2042-8189}, mesh = {Male ; Humans ; Adult ; Middle Aged ; Female ; *COVID-19/epidemiology ; Quality of Life ; Follow-Up Studies ; }, abstract = {BACKGROUND: The long coronavirus disease 2019 (COVID-19) syndrome is defined as persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks following the acute illness.

METHODS: In all, 2,646 patients were randomly selected from all individuals who were diagnosed with COVID-19. They were interviewed so as to assess the persistence of symptoms and health-related quality of life. Blood investigations were also taken.

RESULTS: The median (interquartile range (IQR)) age was 44 (31-55) years and 48.6% were males. Five per cent had been hospitalised. Follow-up was for a median of 142 days (IQR: 128-161). Twenty-two per cent of the participants claimed that they were feeling worse than they felt before COVID-19. The most common symptoms were anosmia, ageusia, fatigue, shortness of breath, headaches and myalgia. The Short Form-36 questionnaire revealed that 16.4% felt that they were somewhat worse than in the previous year and that hospitalised patients fared worse in all domains except for role-emotional. New-onset diabetes was similar to the rate of undiagnosed diabetes in the background population. Hospitalised patients had significantly higher liver transaminases, fasting plasma glucose, glycated haemoglobin, uric acid, red cell distribution width, mean platelet volume, triglyceride levels and troponin levels but lower estimated glomerular filtration rate and high-density lipoprotein-cholesterol at follow-up.

DISCUSSION: A significant proportion of patients were symptomatic at a median follow-up of 142 days and felt worse than 1 year previously. Hospitalised patients had more biochemical and haematological abnormalities compared to non-hospitalised ones, suggesting ongoing inflammation in subjects who were more severely affected by the disease.}, } @article {pmid36369208, year = {2022}, author = {Calabrese, C and Kirchner, E and Calabrese, LH}, title = {Long COVID and rheumatology: Clinical, diagnostic, and therapeutic implications.}, journal = {Best practice & research. Clinical rheumatology}, volume = {36}, number = {4}, pages = {101794}, pmid = {36369208}, issn = {1532-1770}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Rheumatology ; Quality of Life ; COVID-19 Testing ; }, abstract = {As of this writing, it is estimated that there have been nearly 600 million cases of coronavirus disease 2019 (COVID-19) around the world with over six million deaths. While shocking, these figures do not fully illustrate the morbidity associated with this disease. It is also estimated that between 10% and 30% of those who survive COVID-19 develop persistent symptoms after the acute infection has passed. These individuals, who most often experienced initial infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) considered mild to moderate in severity, often display a broad array of symptoms. Collectively, this disorder or syndrome is now referred to as Long COVID (among other designations), and it represents a national/international health crisis. The most frequently reported symptoms associated with Long COVID include chronic fatigue with post exertional features, neurocognitive dysfunction, breathlessness, and somatic pain. Long COVID can range in severity from mild to severely debilitating, with resultant loss of quality of life and productivity. For now, there are many unanswered questions surrounding Long COVID: how can it be best defined, what is needed for accurate diagnosis, what is causing it, and how should it be best managed. How rheumatologists will engage in the Long COVID pandemic is another question; at the minimum, we will be called upon to evaluate and manage our own patients with immune-mediated inflammatory diseases who have developed it. This review focuses on addressing the disease essentials, providing both declarative and procedural knowledge to prepare rheumatologists for how to address Long COVID: understanding its origins, its current case definitions, epidemiology, pathobiology and clinical manifestations. Finally, it will provide an outline on how to clinically approach patients with possible Long COVID and initiate treatment and/or guide them on how to best manage it.}, } @article {pmid36368772, year = {2023}, author = {Kuitunen, I}, title = {Long COVID-19 is rarely diagnosed in children: nationwide register-based analysis.}, journal = {Archives of disease in childhood}, volume = {108}, number = {2}, pages = {151}, doi = {10.1136/archdischild-2022-324998}, pmid = {36368772}, issn = {1468-2044}, mesh = {Child ; Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Registries ; }, } @article {pmid36368518, year = {2023}, author = {Alvarez-Moreno, CA and Pineda, J and Bareño, A and Espitia, R and Rengifo, P}, title = {Long COVID-19 in Latin America: Low prevalence, high resilience or low surveillance and difficulties accessing health care?.}, journal = {Travel medicine and infectious disease}, volume = {51}, number = {}, pages = {102492}, pmid = {36368518}, issn = {1873-0442}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; Prevalence ; Latin America/epidemiology ; Delivery of Health Care ; }, } @article {pmid36367295, year = {2022}, author = {de Roos, MP and Siegerink, S and Dijkstra, NG and Broekman, BF and Brinkman, K and Jonkman, NH and Bresser, P}, title = {Pulmonary function and Quality of Life in a prospective cohort of (non-) hospitalized COVID-19 pneumonia survivors up to six months.}, journal = {Chronic respiratory disease}, volume = {19}, number = {}, pages = {14799731221114271}, pmid = {36367295}, issn = {1479-9731}, mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology ; Prospective Studies ; Survivors ; Lung ; }, abstract = {OBJECTIVES: A decrease of both diffusion capacity (DLCO) and Quality of Life (QoL) was reported after discharge in hospitalized COVID-19 pneumonia survivors. We studied three and 6 month outcomes in hospitalized and non-hospitalized patients.

METHODS: COVID-19 pneumonia survivors (n = 317) were categorized into non-hospitalized "moderate" cases (n = 59), hospitalized "severe" cases (n = 180) and ICU-admitted "critical" cases (n = 39). We studied DLCO and QoL (Short Form SF-36 health survey) 3 and 6 months after discharge. Data were analyzed using (repeated measures) ANOVA, Kruskal-Wallis or Chi-square test (p < .05).

RESULTS: At 3 months DLCO was decreased in 44% of moderate-, 56% of severe- and 82% of critical cases (p < .003). Mean DLCO in critical cases (64±14%) was lower compared to severe (76 ± 17%) and moderate (81±15%) cases (p < .001). A total of 159/278 patients had a decreased DLCO (<80%), of whom the DLCO improved after 6 months in 45% (71/159). However the DLCO did not normalize in the majority (89%) of the cases (63 ± 10% vs 68±10%; p < .001). At 3 months, compared to critical cases, moderate cases scored lower on SF-36 domain "general health" (p < .05); both moderate and severe cases scored lower on the domain of "health change" (p < .05). At 6 months, there were no differences in SF-36 between the subgroups. Compared to 3 months, in all groups "physical functioning" improved; in contrast all groups scored significantly lower on "non-physical" SF-36 domains.

CONCLUSION: Three months after COVID-19 pneumonia, DLCO was still decreased in the more severely affected patients, with an incomplete recovery after 6 months. At 3 months QoL was impaired. At 6 months, while "physical functioning" improved, a decrease in "non-physical" QoL was observed but did not differ between the moderate and severely affected patients.}, } @article {pmid36366465, year = {2022}, author = {Spinicci, M and Graziani, L and Tilli, M and Nkurunziza, J and Vellere, I and Borchi, B and Mencarini, J and Campolmi, I and Gori, L and Giovannoni, L and Amato, C and Livi, L and Rasero, L and Fattirolli, F and Marcucci, R and Giusti, B and Olivotto, I and Tomassetti, S and Lavorini, F and Maggi, L and Annunziato, F and Marchionni, N and Zammarchi, L and Bartoloni, A}, title = {Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.}, journal = {Viruses}, volume = {14}, number = {11}, pages = {}, pmid = {36366465}, issn = {1999-4915}, mesh = {Female ; Humans ; Male ; *COVID-19/epidemiology ; *Fatigue Syndrome, Chronic/complications ; Pandemics ; Phenotype ; Retrospective Studies ; SARS-CoV-2/genetics ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.}, } @article {pmid36362782, year = {2022}, author = {De Luca, R and Bonanno, M and Calabrò, RS}, title = {Psychological and Cognitive Effects of Long COVID: A Narrative Review Focusing on the Assessment and Rehabilitative Approach.}, journal = {Journal of clinical medicine}, volume = {11}, number = {21}, pages = {}, pmid = {36362782}, issn = {2077-0383}, abstract = {Long COVID is a clinical syndrome characterized by profound fatigue, neurocognitive difficulties, muscle pain, weakness, and depression, lasting beyond the 3-12 weeks following infection with SARS-CoV-2. Among the symptoms, neurocognitive and psychiatric sequelae, including attention and memory alterations, as well as anxiety and depression symptoms, have become major targets of current healthcare providers given the significant public health impact. In this context, assessment tools play a crucial role in the early screening of cognitive alterations due to Long COVID. Among others, the general cognitive assessment tools, such as the Montreal Cognitive assessment, and more specific ones, including the State Trait Inventory of Cognitive Fatigue and the Digit Span, may be of help in investigating the main neurocognitive alterations. Moreover, appropriate neurorehabilitative programs using specific methods and techniques (conventional and/or advanced) through a multidisciplinary team are required to treat COVID-19-related cognitive and behavioral abnormalities. In this narrative review, we sought to describe the main neurocognitive and psychiatric symptoms as well as to provide some clinical advice for the assessment and treatment of Long COVID.}, } @article {pmid36362710, year = {2022}, author = {Pauwen, NY and Faoro, V and Boucharessas, F and Colot, T and Guillaume, A and Sergysels, R and Ninane, V}, title = {Validation Criteria for PETCO2 Kinetics during the Hyperventilation Provocation Test in the Diagnosis of Idiopathic Hyperventilation Syndrome.}, journal = {Journal of clinical medicine}, volume = {11}, number = {21}, pages = {}, pmid = {36362710}, issn = {2077-0383}, abstract = {Background: The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ). Methods: The kinetics of PETCO2 during the HPTest were mathematically modeled and compared between 37 HVS patients (NQ ≥23/64) and 37 healthy controls (NQ <23/64) matched for gender, age, and body dimensions. AUC values with sensitivity and specificity were calculated, and analysis was monitored in a validation cohort of 152 routine HPTests. Results: A threshold value of a less than 12.8 mmHg increment of PETCO2 at the 5th minute of the recovery phase of the HPTest diagnosed HVS patients with excellent sensitivity (0.92) and specificity (0.84). These results were confirmed in the validation cohort, highlighting the presence of 24% false positives/negatives when diagnosing on the basis of complaints in the NQ. Conclusions: For HVS diagnosis, we suggest considering the HPTest, which can more reliably reflect the mechanisms of CO2 homeostasis and the response of the respiratory center to a stimulus, regardless of the subjective onset of symptoms.}, } @article {pmid36362706, year = {2022}, author = {Tarazona, V and Kirouchena, D and Clerc, P and Pinsard-Laventure, F and Bourrion, B}, title = {Quality of Life in COVID-19 Outpatients: A Long-Term Follow-Up Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {21}, pages = {}, pmid = {36362706}, issn = {2077-0383}, abstract = {Background: The long-term issues faced by COVID-19 survivors remain unclear. Symptoms may persist for several months, even in non-hospitalized patients, probably impacting the quality of life. Objective: To assess the health-related quality of life of outpatients one year after SARS-CoV-2 infection. Design, Settings, and Participants: This prospective multicentre study, conducted in France from February 2020 to February 2022, compared 150 COVID-19 cases (PCR+ and/or CT scan+) and 260 controls (PCR-) selected from a database of four COVID centres. Main outcomes: Health-related quality of life assessed using the EQ-5D-5L scale. Results: COVID-19 outpatients (n = 96) had significantly lower health-related quality of life than controls (n = 81) one year after SARS-CoV-2 infection: the EQ-5D-5L index averaged 0.87 in cases and 0.95 in controls (p = 0.002); the EQ- VAS averaged 78 in cases and 86.7 in controls (p < 0.001). This alteration in quality of life was more intense in the areas of pain or discomfort and daily activities. Conclusions: This study is the first to show an alteration in the quality of life of COVID-19 outpatients after one year. Appropriate guidance and community rehabilitation programs are required for outpatients with persistent symptoms of COVID-19. Research must continue to confirm these results in larger cohorts.}, } @article {pmid36362684, year = {2022}, author = {Hirahata, K and Nawa, N and Fujiwara, T}, title = {Characteristics of Long COVID: Cases from the First to the Fifth Wave in Greater Tokyo, Japan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {21}, pages = {}, pmid = {36362684}, issn = {2077-0383}, abstract = {PURPOSE: Approximately 25-60% of COVID-19 patients develop long-term sequelae of the condition known as long COVID. This study aimed to examine sociodemographic and clinical characteristics of long COVID in Japan.

METHODS: The data of long COVID patients, defined as those who were symptomatic after 28 days from onset, were collected in an outpatient clinic in Tokyo, Japan between 6 January 2020 and 2 October 2021 (N = 1891). Information on age, sex, employment, infection waves, vaccination, impairment in activities of daily living, and symptoms were obtained from electronic medical records. We used linear regression to analyze the association of patients characteristics with performance status.

RESULTS: The mean number of days from onset was 77.6 (SD: 71.3). Female, those who had their work hours reduced, on leave, dismissed or retired or not working, were associated with lower performance status. Fatigue, depressive symptom, brain fog, dyspnea, palpitation, body pain, loss of appetite, fever-but not headache, insomnia, loss of smell, loss of taste, hair loss, or cough-were associated with the lower performance status.

CONCLUSION: Sex and employment status were associated with lower performance status in long COVID patients. Studies are needed to elucidate the full picture of the characteristics of long COVID patients.}, } @article {pmid36361430, year = {2022}, author = {Duradoni, M and Gursesli, MC and Materassi, L and Serritella, E and Guazzini, A}, title = {The Long-COVID Experience Changed People's Vaccine Hesitancy but Not Their Vaccination Fear.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {21}, pages = {}, pmid = {36361430}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines/therapeutic use ; Vaccination Hesitancy ; Pandemics ; Patient Acceptance of Health Care ; Vaccination ; *Vaccines ; Fear ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Starting in early 2020, the COVID-19 pandemic has been responsible, worldwide, for millions of deaths and patients with long-COVID syndrome. In an attempt to stop the spread of the virus, the blanket administration of COVID-19 vaccines proved to be the most effective measure, yet the existence and availability of functional vaccines did not and, still, do not ensure the willingness and intent of people to be vaccinated. This study assessed the similarities and differences in vaccine fears and vaccine hesitancy through between clusters of subjects: people that were not infected with COVID-19, people that had COVID but did not develop long-lasting symptoms, and people that were infected with COVID and developed long-COVID syndrome. From the sample of 1111 Italian people, it was found that individuals who experienced mild symptoms showed higher vaccine hesitancy (confidence, complacency, and collective responsibility) than those who did not contract COVID-19. People affected by long-COVID showed a lower overall hesitancy than individuals who had COVID-19 without incurring long-lasting symptoms and, thus, essentially resembled people who had no experience of COVID-19 infection in terms of the vaccine hesitancy scores. Vaccine fear remained unchanged across all three of the examined clusters.}, } @article {pmid36361362, year = {2022}, author = {Ogonowska-Slodownik, A and Labecka, MK and Kaczmarczyk, K and McNamara, RJ and Starczewski, M and Gajewski, J and Maciejewska-Skrendo, A and Morgulec-Adamowicz, N}, title = {Water-Based and Land-Based Exercise for Children with Post-COVID-19 Condition (postCOVIDkids)-Protocol for a Randomized Controlled Trial.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {21}, pages = {}, pmid = {36361362}, issn = {1660-4601}, mesh = {Child ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Quality of Life ; Prospective Studies ; Water ; Fatigue ; Dyspnea/etiology ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {The most common symptoms of post-COVID-19 condition in children are fatigue, shortness of breath, exercise intolerance, and weakness. The post-COVID-19 condition in children can be very debilitating and lead to prolonged school absences, high morbidity, and limitations in daily functioning. The aim of this research project is to determine the effectiveness of land-based and water-based exercise interventions on exercise capacity, fatigue, health-related quality of life, and pulmonary function in children with post-COVID-19 condition. This study is a prospective randomized controlled study with pre- and post-intervention assessment. Participants will be recruited from Warsaw's primary schools and primary healthcare units according to the inclusion criteria: (i) symptoms of post-COVID-19 condition lasting more than one month following initial COVID-19 infection confirmed by the diagnosis by general practitioner (including obligatory fatigue and shortness of breath/respiratory problems); (ii) age 10-12 years old. Participants meeting the inclusion criteria will be randomized to one of three groups: water-based exercise, land-based exercise, or control (no exercise). We hope this study will provide guidance for long-COVID-19 rehabilitation in children.}, } @article {pmid36360651, year = {2022}, author = {Speichert, LJ and Schweda, A and Witzke, O and Konik, M and Rohn, H and Stettner, M and Musche, V and Herchert, K and Fink, M and Geiger, S and Bäuerle, A and Skoda, EM and Teufel, M and Dinse, H}, title = {Fear of Death during COVID-19 Does Not Explain Post-Infection Depression Symptoms beyond Reported Symptoms during the Infection in COVID-19 Survivors.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {21}, pages = {}, pmid = {36360651}, issn = {1660-4601}, mesh = {*COVID-19/epidemiology ; Cross-Sectional Studies ; SARS-CoV-2 ; Pandemics ; Humans ; Depression/epidemiology/etiology/psychology ; *Medically Unexplained Symptoms ; Female ; COVID-19 Testing ; Survivors ; Anxiety/psychology ; Phobic Disorders ; }, abstract = {The COVID-19 pandemic poses an unprecedented global burden to the general population and, in particular, to individuals who have been infected with SARS-CoV-2. In the context of the discussion about "post COVID-19", the aim of the study was to advance research on mental health and long-term consequences after COVID-19. In total, 214 COVID-19 survivors (female: 54.2%; hospitalized: 36.7%) participated in the repeated cross-sectional assessment. In addition to demographic data, mental and somatic symptoms, fear of death at the time of infection, and depressive (PHQ-8) and generalized anxiety symptoms (GAD-7) were assessed. Results showed an increased prevalence of depressive symptoms and symptoms of generalized anxiety compared to observations in the general population prior to the COVID-19 pandemic. Psychological symptoms of depression and reported levels of fear of death during the SARS-CoV-2 infection showed a negative association with the time interval since COVID-19 diagnosis. Furthermore, although fear of death during the acute COVID-19 was related to depression and generalized anxiety, this association was predominantly explained by the presence of mental and somatic symptoms. In conclusion, initial fear of death does not impact mental health beyond the overall symptom burden. Furthermore, depressive symptoms appear to vanish across time since infection.}, } @article {pmid36360494, year = {2022}, author = {Allado, E and Poussel, M and Hamroun, A and Moussu, A and Kneizeh, G and Hily, O and Temperelli, M and Corradi, C and Koch, A and Albuisson, E and Chenuel, B}, title = {Is There a Relationship between Hyperventilation Syndrome and History of Acute SARS-CoV-2 Infection? A Cross-Sectional Study.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {36360494}, issn = {2227-9032}, abstract = {Following COVID-19 infection, many patients suffer from long-lasting symptoms that may greatly impair their quality of life. Persisting dyspnea and other functional respiratory complaints can evoke hyperventilation syndrome (HVS) as a putative contributor to long-COVID presentation in COVID-19 survivors. We aimed to assess the possible relationship between HVS and previous acute COVID-19 infection. We designed a cross-sectional, single-center study, including all patients consecutively referred to our Lung Function and Exercise Testing Department between January and June 2021. Participants completed a systematic Nijmegen Questionnaire, a modified Medical Research Council dyspnea scale assessment, a post-COVID screening questionnaire, and performed a standardized lung function test. The population was divided according to HVS diagnosis, defined as a Nijmegen score of > 23/64. The occurrence of previous COVID-19 infection was compared according to the Nijmegen score after adjustment for potential confounders by multivariate logistic regression. In total, 2846 patients were included: 1472 men (51.7%) with a mean age of 56 (±16.6) years. A total of 455 patients (16%) declared a previous SARS-CoV-2 infection, and 590 patients presented a positive score (>23/64) in the Nijmegen Questionnaire (20.7%). Compared with COVID-19-free patients, there was an increased occurrence of HVS+ in cases of COVID-19 infection that did not require hospitalization (aOR = 1.93 [1.17−3.18]). The results of this large-scale, cross-sectional study suggest an association between HVS diagnosis and a history of COVID-19 disease in patients who were not hospitalized.}, } @article {pmid36360471, year = {2022}, author = {Al-Mhanna, SB and Mohamed, M and Noor, NM and Afolabi, HA and Irekeola, AA and Bello, KE and Aldhahi, MI and Wan Ghazali, WS}, title = {Effectiveness of Pulmonary Rehabilitation among COVID-19 Patients: A Systematic Review and Meta-Analysis.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {36360471}, issn = {2227-9032}, abstract = {Background: Many COVID-19 patients presented with detrimental features, such as impaired respiratory function, physical capacity, and overall poor quality of life. The present study evaluates the effectiveness of pulmonary rehabilitation on COVID-19 patients. Methods: We searched PubMed, Scopus, ScienceDirect, and Google Scholar from 2019 to 2021. The protocol was registered in PROSPERO with the registration number CRD42021273618. We performed statistical analyses via random effects and expressed the outcomes as standardized mean difference (SMD) for continuous variables, with 95% confidence intervals (CI). Results: We included six trials involving 432 patients. The primary outcome showed a significant improvement in physical function (SMD 0.83, 95% CI −0.58 to 1.09; p < 0.001; four trials, 266 participants; high-quality evidence). There was significant difference in anxiety (SMD −0.80, 95% CI −1.23 to −0.37; p = 0.003), physical activity intensity levels (SMD −1.27, 95% CI −2.23 to −0.32; p = 0.009), sleep quality (MD −0.05, 95% CI −0.83 to −0.16; p = 0.004), peripheral muscle performance of lower limbs (SMD 0.90, 95% CI −0.60 to 1.20; p < 0.001), and dyspnoea outcomes (SMD −0.55, 95% CI −0.87 to −0.23; p = 0.007). Conclusions: Pulmonary rehabilitation is an effective adjuvant therapy that minimizes COVID-19 severity in the intervention group compared to the conventional treatment. The findings of this study will need to be considered in the framework of the clinical outcome as observed in the intervention outcome. Additionally, safer data on guideline rehabilitation would be needed to examine whether pulmonary rehabilitation would be a fruitful intervention to reduce COVID-19 severity.}, } @article {pmid36360405, year = {2022}, author = {Gonzalez-Aumatell, A and Bovo, MV and Carreras-Abad, C and Cuso-Perez, S and Domènech Marsal, È and Coll-Fernández, R and Goicoechea Calvo, A and Giralt-López, M and Enseñat Cantallops, A and Moron-Lopez, S and Martinez-Picado, J and Sol Ventura, P and Rodrigo, C and Méndez Hernández, M}, title = {Social, Academic, and Health Status Impact of Long COVID on Children and Young People: An Observational, Descriptive, and Longitudinal Cohort Study.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {11}, pages = {}, pmid = {36360405}, issn = {2227-9067}, abstract = {There is a lack of evidence of the health impacts due to long COVID among children and young people (CYP). The objective of this study is to determine the main clinical characteristics of long COVID in CYP and to investigate the academic, social, and health status impacts of long COVID in this population. An observational, descriptive, and longitudinal study on CYP who presented COVID-19 symptoms for more than twelve weeks after SARS-CoV-2 infection was performed between December 2020 and May 2021. Fifty CYP were included, with a median age of 14.1 years, 33 (66%) were female, and 17 (34%) had a relative diagnosed with long COVID. Since the initial infection and up to the first visit, CYP had persisting symptoms for a median of 4.1 months, and for 18 (36%) CYP these symptoms persisted for more than 6 months. Fatigue (100%), neurocognitive disorders (74%), muscular weakness (74%), and headache (72%) were the most reported symptoms. A total of 9 (18%) CYP could not attend school, 17 (34%) had a reduced schedule, 33 (66%) showed a decreased school performance, and 68% had stopped extracurricular activities. This preliminary study shows the impact that long COVID has on the health, academic, and social life of CYP.}, } @article {pmid36360172, year = {2022}, author = {Fernández-de-Las-Peñas, C and Arendt-Nielsen, L and Díaz-Gil, G and Gómez-Esquer, F and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Palomar-Gallego, MA and Pellicer-Valero, OJ and Giordano, R}, title = {Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.}, journal = {Genes}, volume = {13}, number = {11}, pages = {}, pmid = {36360172}, issn = {2073-4425}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Angiotensin-Converting Enzyme 2/genetics ; *COVID-19/genetics ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Single Nucleotide ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 virus into the cells, so polymorphisms could be important for the prognoses of long-COVID symptoms. Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) individuals who had been previously hospitalized due to COVID-19 were included. Three potential genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva samples of participants: ACE2 (rs2285666), ACE2 (rs2074192), TMPRSS2 (rs12329760), TMPRSS2 (rs2070788). Participants were asked to self-report the presence of any post-COVID defined as a symptom that started no later than one month after SARS-CoV-2 acute infection and whether the symptom persisted at the time of the study. At the time of the study (mean: 17.8, SD: 5.2 months after hospital discharge), 87.7% patients reported at least one symptom. Fatigue (62.8%), pain (39.9%) or memory loss (32.1%) were the most prevalent post-COVID symptoms. Overall, no differences in long-COVID symptoms were dependent on ACE2 rs2285666, ACE2 rs2074192, TMPRSS2 rs12329760, or TMPRSS2 rs2070788 genotypes. The four SNPs assessed, albeit previously associated with COVID-19 severity, do not predispose for developing long-COVID symptoms in people who were previously hospitalized due to COVID-19 during the first wave of the pandemic.}, } @article {pmid36359409, year = {2022}, author = {Fiedler, L and Motloch, LJ and Jirak, P and Gumerov, R and Davtyan, P and Gareeva, D and Lakman, I and Tataurov, A and Lasinova, G and Pavlov, V and Hauptmann, L and Kopp, K and Hoppe, UC and Lichtenauer, M and Pistulli, R and Dieplinger, AM and Zagidullin, N}, title = {Investigation of hs-TnI and sST-2 as Potential Predictors of Long-Term Cardiovascular Risk in Patients with Survived Hospitalization for COVID-19 Pneumonia.}, journal = {Biomedicines}, volume = {10}, number = {11}, pages = {}, pmid = {36359409}, issn = {2227-9059}, support = {22-25-00019//Russian Science Foundation/ ; }, abstract = {Introduction: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. Methods: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. Results: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7% & specificity = 65.7%; sST-2: sensitivity = 33.3% & specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012−1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904−12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI = 4.509−29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). Conclusion: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.}, } @article {pmid36358996, year = {2022}, author = {Cardinali, DP and Brown, GM and Pandi-Perumal, SR}, title = {Possible Application of Melatonin in Long COVID.}, journal = {Biomolecules}, volume = {12}, number = {11}, pages = {}, pmid = {36358996}, issn = {2218-273X}, mesh = {Humans ; *Melatonin/therapeutic use ; SARS-CoV-2 ; *Fatigue Syndrome, Chronic/drug therapy/diagnosis ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, "long COVID". Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or "brain fog"), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration ("brain fog") and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.}, } @article {pmid36358582, year = {2022}, author = {Hepburn, J and Williams-Lockhart, S and Bensadoun, RJ and Hanna, R}, title = {A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {36358582}, issn = {2076-3921}, abstract = {Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021-August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm[2] for PDI and 4.9 J/cm[2] for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12-24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of "long COVID" symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.}, } @article {pmid36355754, year = {2022}, author = {Roessler, M and Tesch, F and Batram, M and Jacob, J and Loser, F and Weidinger, O and Wende, D and Vivirito, A and Toepfner, N and Ehm, F and Seifert, M and Nagel, O and König, C and Jucknewitz, R and Armann, JP and Berner, R and Treskova-Schwarzbach, M and Hertle, D and Scholz, S and Stern, S and Ballesteros, P and Baßler, S and Bertele, B and Repschläger, U and Richter, N and Riederer, C and Sobik, F and Schramm, A and Schulte, C and Wieler, L and Walker, J and Scheidt-Nave, C and Schmitt, J}, title = {Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.}, journal = {PLoS medicine}, volume = {19}, number = {11}, pages = {e1004122}, pmid = {36355754}, issn = {1549-1676}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Cohort Studies ; *COVID-19/epidemiology ; COVID-19 Testing ; Germany/epidemiology ; Morbidity ; Retrospective Studies ; Young Adult ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults.

METHODS AND FINDINGS: We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias.

CONCLUSIONS: In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults.

TRIAL REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.}, } @article {pmid36355108, year = {2022}, author = {Guntur, VP and Nemkov, T and de Boer, E and Mohning, MP and Baraghoshi, D and Cendali, FI and San-Millán, I and Petrache, I and D'Alessandro, A}, title = {Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC).}, journal = {Metabolites}, volume = {12}, number = {11}, pages = {}, pmid = {36355108}, issn = {2218-1989}, support = {R01 HL146442/HL/NHLBI NIH HHS/United States ; RM1 GM131968/GM/NIGMS NIH HHS/United States ; R01 HL077328/HL/NHLBI NIH HHS/United States ; T32 HL007085/HL/NHLBI NIH HHS/United States ; R01 HL148151/HL/NHLBI NIH HHS/United States ; R21 HL150032/HL/NHLBI NIH HHS/United States ; R01 HL149714/HL/NHLBI NIH HHS/United States ; RM1GM131968/GM/NIGMS NIH HHS/United States ; R01 HL161004/HL/NHLBI NIH HHS/United States ; }, abstract = {Exercise intolerance is a major manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus infection (PASC, or "long-COVID"). Exercise intolerance in PASC is associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism and mitochondrial dysfunction. It remains unclear whether the profound disturbances in metabolism that have been identified in plasma from patients suffering from acute coronavirus disease 2019 (COVID-19) are also present in PASC. To bridge this gap, individuals with a history of previous acute COVID-19 infection that did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) and were grouped into those that developed PASC (n = 29) and those that fully recovered (n = 16). Plasma samples from the two groups were analyzed via mass spectrometry-based untargeted metabolomics and compared against plasma metabolic profiles of healthy control individuals (n = 30). Observational demographic and clinical data were retrospectively abstracted from the medical record. Compared to plasma of healthy controls or individuals who recovered from COVID-19, PASC plasma exhibited significantly higher free- and carnitine-conjugated mono-, poly-, and highly unsaturated fatty acids, accompanied by markedly lower levels of mono-, di- and tricarboxylates (pyruvate, lactate, citrate, succinate, and malate), polyamines (spermine) and taurine. Plasma from individuals who fully recovered from COVID-19 exhibited an intermediary metabolic phenotype, with milder disturbances in fatty acid metabolism and higher levels of spermine and taurine. Of note, depletion of tryptophan-a hallmark of disease severity in COVID-19-is not normalized in PASC patients, despite normalization of kynurenine levels-a tryptophan metabolite that predicts mortality in hospitalized COVID-19 patients. In conclusion, PASC plasma metabolites are indicative of altered fatty acid metabolism and dysfunctional mitochondria-dependent lipid catabolism. These metabolic profiles obtained at rest are consistent with previously reported mitochondrial dysfunction during exercise, and may pave the way for therapeutic intervention focused on restoring mitochondrial fat-burning capacity.}, } @article {pmid36354180, year = {2022}, author = {Mesias, VSD and Zhu, H and Tang, X and Dai, X and Liu, W and Guo, Y and Huang, J}, title = {Moderate Binding between Two SARS-CoV-2 Protein Segments and α-Synuclein Alters Its Toxic Oligomerization Propensity Differently.}, journal = {The journal of physical chemistry letters}, volume = {13}, number = {45}, pages = {10642-10648}, pmid = {36354180}, issn = {1948-7185}, mesh = {Humans ; *alpha-Synuclein/metabolism ; *COVID-19 ; *Parkinson Disease/metabolism ; Protein Binding ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus/metabolism ; *Coronavirus Envelope Proteins/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {The neurological symptoms of long COVID and viral neuroinvasion have raised concerns about the potential interactions between SARS-CoV-2 protein segments and neuronal proteins, which might confer a risk of post-infection neurodegeneration, but the underlying mechanisms remain unclear. Here, we reported that the receptor-binding domain (RBD) of the spike protein and the nine-residue segment (SK9) of the envelope protein could bind to α-synuclein (αSyn) with Kd values of 503 ± 24 nM and 12.7 ± 1.6 μM, respectively. RBD could inhibit αSyn fibrillization by blocking the non-amyloid-β component region and mediating its antiparallel β-sheet structural conversions. Omicron-RBD (BA.5) was shown to have a slightly stronger affinity for αSyn (Kd = 235 ± 10 nM), which implies similar effects, whereas SK9 may bind to the C-terminus which accelerates the formation of parallel β-sheet-containing oligomers and abruptly increases the rate of membrane disruption by 213%. Our results provide plausible molecular insights into the impact of SARS-CoV-2 post-infection and the oligomerization propensity of αSyn that is associated with Parkinson's disease.}, } @article {pmid36353967, year = {2023}, author = {Corvol, H and Prevost, B and Aubertin, G and Thouvenin, G and Taytard, J and Nathan, N}, title = {COVID-19 and pediatric pulmonology: Feedback from an expert center after the first year of the pandemic.}, journal = {Pediatric pulmonology}, volume = {58}, number = {2}, pages = {392-397}, pmid = {36353967}, issn = {1099-0496}, mesh = {Young Adult ; Humans ; Child ; Adolescent ; Aged ; *COVID-19 ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; Feedback ; *Pulmonary Medicine ; }, abstract = {The coronavirus disease 2019 (COVID-19) outbreak has evolved with different waves corresponding to subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. While the most severe cases have been observed in the elderly and in individuals with underlying comorbidities, severe pediatric and young adult cases have been observed, as well as post-infectious inflammatory syndromes and persistent symptoms leading to long-COVID. This manuscript describes the experience of a pediatric respiratory unit during the first year of the pandemic and reviews the corresponding literature with a special emphasis on children and young people with underlying conditions, such as immunosuppression, sickle cell disease, and cystic fibrosis.}, } @article {pmid36353225, year = {2022}, author = {Pływaczewska-Jakubowska, M and Chudzik, M and Babicki, M and Kapusta, J and Jankowski, P}, title = {Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1036556}, pmid = {36353225}, issn = {2296-858X}, abstract = {INTRODUCTION: The coronavirus disease (COVID) 2019 pandemic remains a great challenge for the healthcare system. The widely reported prolonged signs and symptoms resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (Long-COVID) require medical care. The aim of the study was to assess factors, including lifestyle variables, related to the course of COVID-19 infection and to assess their impact on prolonged symptoms in non-hospitalized patients with COVID-19.

METHODS: A total of 1,847 (637 men and 1,210 women) non-hospitalized participants of the STOP-COVID registry of the PoLoCOV-Study who, following the COVID-19, underwent check-up examinations at the cardiology outpatient clinic were included in the analysis.

RESULTS: The study participants (median age 51 [41-62] years) were evaluated at 13.4 (8.4-23.6) weeks following the diagnosis of COVID-19. Female sex (odds ratio [OR] 1.46 [95% CI 1.19-1.78]), body mass index (BMI; per 1 kg/m[2]: 1.02 [1.00-1.04]), hypertension (1.39 [1.07-1.81]), asthma (1.55 [1.06-2.27]), stress or overworking (1.54 [1.25-1.90]), and nightshift work (1.51 [1.06-2.14]) were independently related to the severity of symptoms during acute phase of the COVID-19 infection. The Long-COVID syndrome was independently related to the female sex (1.42 [1.13-1.79]), history of myocardial infarction (2.57 [1.04-6.32]), asthma (1.56 [1.01-2.41]), and severe course of the acute phase of the COVID-19 infection (2.27 [1.82-2.83]).

CONCLUSION: Female sex, BMI, asthma, hypertension, nightshifts, and stress or overworking are significantly related to the severity of the acute phase of the COVID-19 infection, while female sex, asthma, history of myocardial infarction, and the severity of symptoms in the acute phase of COVID-19 are the predictors of Long-COVID in non-hospitalized patients. We did not find an independent relation between Long-COVID and the studied lifestyle factors.}, } @article {pmid36353127, year = {2022}, author = {Larsen, NW and Stiles, LE and Shaik, R and Schneider, L and Muppidi, S and Tsui, CT and Geng, LN and Bonilla, H and Miglis, MG}, title = {Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {1012668}, pmid = {36353127}, issn = {1664-2295}, support = {R25 AI147369/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.

OBJECTIVE: To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.

DESIGN: Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.

PARTICIPANTS: 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.

MAIN MEASURES: The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.

KEY RESULTS: Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].

CONCLUSIONS: Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.}, } @article {pmid36352492, year = {2022}, author = {Dirican, E and Bal, T}, title = {COVID-19 disease severity to predict persistent symptoms: a systematic review and meta-analysis.}, journal = {Primary health care research & development}, volume = {23}, number = {}, pages = {e69}, pmid = {36352492}, issn = {1477-1128}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Dyspnea/diagnosis/etiology ; Fatigue/diagnosis/etiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is unclear, whether the initial disease severity may help to predict which COVID-19 patients at risk of developing persistent symptoms.

AIM: The aim of this study was to examine whether the initial disease severity affects the risk of persistent symptoms in post-acute COVID-19 syndrome and long COVID.

METHODS: A systematic search was conducted using PUBMED, Google Scholar, EMBASE, and ProQuest databases to identify eligible articles published after January 2020 up to and including 30 August 2021. Pooled odds ratio (OR) and confidence intervals (CIs) were calculated using random effects meta-analysis.

FINDINGS: After searching a total of 7733 articles, 20 relevant observational studies with a total of 7840 patients were selected for meta-analysis. The pooled OR for persistent dyspnea in COVID-19 survivors with a severe versus nonsevere initial disease was 2.17 [95%CI 1.62 to 2.90], and it was 1.33 [95%CI 0.75 to 2.33] for persistent cough, 1.30 [95%CI 1.06 to 1.58] for persistent fatigue, 1.02 [95%CI 0.73 to 1.40] for persistent anosmia, 1.22 [95%CI 0.69 to 2.16] for persistent chest pain, and 1.30 [95%CI 0.93 to 1.81] for persistent palpitation.

CONCLUSIONS: Contrary to expectations, we did not observe an association between the initial COVID-19 disease severity and common persistent symptoms except for dyspnea and fatigue. In addition, it was found that being in the acute or prolonged post-COVID phase did not affect the risk of symptoms. Primary care providers should be alert to potential most prevalent persistent symptoms in all COVID-19 survivors, which are not limited to patients with critical-severe initial disease.}, } @article {pmid36352367, year = {2022}, author = {Moura, AEF and Oliveira, DN and Torres, DM and Tavares-Júnior, JWL and Nóbrega, PR and Braga-Neto, P and Sobreira-Neto, MA}, title = {Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long COVID syndrome - a prospective cohort study.}, journal = {BMC neurology}, volume = {22}, number = {1}, pages = {417}, pmid = {36352367}, issn = {1471-2377}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/epidemiology ; *COVID-19/complications/epidemiology ; Prospective Studies ; Sleepiness ; *Disorders of Excessive Somnolence/diagnosis/epidemiology ; *Sleep Wake Disorders/epidemiology ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome.

METHODOLOGY: A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness.

RESULTS: Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients.

CONCLUSION: Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.}, } @article {pmid36351871, year = {2022}, author = {Raveendran, AV and Jayadevan, R and Sashidharan, S}, title = {Erratum to "Long COVID: An overview" [Diabetes Metabol. Syndr. Clin. Res. Rev. (2021) 869-875].}, journal = {Diabetes & metabolic syndrome}, volume = {16}, number = {12}, pages = {102660}, doi = {10.1016/j.dsx.2022.102660}, pmid = {36351871}, issn = {1878-0334}, } @article {pmid36351274, year = {2022}, author = {Venkataramani, V and Winkler, F}, title = {Cognitive Deficits in Long Covid-19.}, journal = {The New England journal of medicine}, volume = {387}, number = {19}, pages = {1813-1815}, doi = {10.1056/NEJMcibr2210069}, pmid = {36351274}, issn = {1533-4406}, mesh = {Humans ; Cognition ; Cognition Disorders/etiology ; *Cognitive Dysfunction/etiology ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36350613, year = {2023}, author = {Chen, Q and Allot, A and Leaman, R and Wei, CH and Aghaarabi, E and Guerrerio, JJ and Xu, L and Lu, Z}, title = {LitCovid in 2022: an information resource for the COVID-19 literature.}, journal = {Nucleic acids research}, volume = {51}, number = {D1}, pages = {D1512-D1518}, pmid = {36350613}, issn = {1362-4962}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; United States ; *Databases, Bibliographic ; }, abstract = {LitCovid (https://www.ncbi.nlm.nih.gov/research/coronavirus/)-first launched in February 2020-is a first-of-its-kind literature hub for tracking up-to-date published research on COVID-19. The number of articles in LitCovid has increased from 55 000 to ∼300 000 over the past 2.5 years, with a consistent growth rate of ∼10 000 articles per month. In addition to the rapid literature growth, the COVID-19 pandemic has evolved dramatically. For instance, the Omicron variant has now accounted for over 98% of new infections in the United States. In response to the continuing evolution of the COVID-19 pandemic, this article describes significant updates to LitCovid over the last 2 years. First, we introduced the long Covid collection consisting of the articles on COVID-19 survivors experiencing ongoing multisystemic symptoms, including respiratory issues, cardiovascular disease, cognitive impairment, and profound fatigue. Second, we provided new annotations on the latest COVID-19 strains and vaccines mentioned in the literature. Third, we improved several existing features with more accurate machine learning algorithms for annotating topics and classifying articles relevant to COVID-19. LitCovid has been widely used with millions of accesses by users worldwide on various information needs and continues to play a critical role in collecting, curating and standardizing the latest knowledge on the COVID-19 literature.}, } @article {pmid36350150, year = {2022}, author = {Fogh, K and Larsen, TG and Hansen, CB and Hasselbalch, RB and Eriksen, ARR and Bundgaard, H and Frikke-Schmidt, R and Hilsted, LM and Østergaard, L and Johansen, IS and Hageman, I and Garred, P and Iversen, K}, title = {Self-Reported Long COVID and Its Association with the Presence of SARS-CoV-2 Antibodies in a Danish Cohort up to 12 Months after Infection.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0253722}, pmid = {36350150}, issn = {2165-0497}, mesh = {Humans ; Female ; Middle Aged ; Adolescent ; Male ; *Post-Acute COVID-19 Syndrome ; Self Report ; SARS-CoV-2 ; Cohort Studies ; Pandemics ; *COVID-19/epidemiology ; Antibodies, Viral ; Denmark/epidemiology ; }, abstract = {The majority of long coronavirus disease (COVID) symptoms are not specific to COVID-19 and could be explained by other conditions. The present study aimed to explore whether Danish individuals with a perception that they suffer from long COVID have antibodies against the nucleocapsid antigen, as a proxy for detecting previous infection. The study was conducted in February and March 2021, right after the second surge of the COVID-19 pandemic in Denmark. All members of the social media group on Facebook "Covidramte med senfølger" ("long COVID sufferers'') above the age of 17 years and living in Denmark were invited to participate in a short electronic questionnaire about long COVID risk factors and symptoms. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein was detected in blood samples as a proxy for natural SARS-CoV-2 infection. The final study population comprised 341 participants (90.6% females) who completed blood sampling and answered the questionnaire. A total of 232 (68%) were seropositive (median age, 49.5 years; interquartile range [IQR], 41 to 55 years; 90.1% females). There was no significant difference between sexes and serostatus. Seronegative and seropositive individuals had a similar burden of symptoms that could be attributed to long COVID. Time since perceived COVID-19 was significantly longer in the group of seronegative individuals than the seropositive ones (P < 0.001). This study suggests that long-COVID sufferers are mostly women and showed that a third of the participants did not have detectable anti-N-protein antibodies. It emphasizes the importance of early confirmation of COVID-19, as this study indicates an overlap between long-COVID symptoms and symptoms that are possibly of another origin. IMPORTANCE This cohort study included questionnaire data as well as anti-nucleocapsid antibody analysis, allowing us to determine whether participants were seropositive due to vaccination or natural infection. The study emphasizes the importance of early confirmation of COVID-19, as antibodies recede with time, and it indicates an overlap between long COVID symptoms and symptoms possibly of another origin.}, } @article {pmid36349400, year = {2023}, author = {Chee, YJ and Fan, BE and Young, BE and Dalan, R and Lye, DC}, title = {Clinical trials on the pharmacological treatment of long COVID: A systematic review.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28289}, pmid = {36349400}, issn = {1096-9071}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Multiple Organ Failure ; }, abstract = {The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome. A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.}, } @article {pmid36348978, year = {2023}, author = {Safronenka, A and Capcha, JMC and Webster, KA and Buglo, E and Tamariz, L and Goldberger, JJ and Shehadeh, LA}, title = {Autoimmune Reaction Associated With Long COVID Syndrome and Cardiovascular Disease: A Genetic Case Report.}, journal = {JACC. Case reports}, volume = {6}, number = {}, pages = {101644}, pmid = {36348978}, issn = {2666-0849}, support = {R01 HL140468/HL/NHLBI NIH HHS/United States ; }, abstract = {A 35-year-old woman with history of cardiovascular disease presented with shortness of breath, lightheadedness, fatigue, chest pain, and premature ventricular contractions 3 weeks after her second COVID-19 vaccine. Symptoms subsided following catheter ablation and ibuprofen except for chest pain and fatigue, which persisted following ablation and subsequent SARS-CoV-2 infection. The case suggests causal associations between COVID-19 vaccine/infection and recurrence of cardiovascular disease, including long-COVID-like symptoms. (Level of Difficulty: Advanced.).}, } @article {pmid36347517, year = {2022}, author = {Jung, J}, title = {Preparations for the Assessment of COVID-19 Infection and Long-Term Cardiovascular Risk.}, journal = {Korean circulation journal}, volume = {52}, number = {11}, pages = {808-813}, pmid = {36347517}, issn = {1738-5520}, support = {NRF-2021R1C1C101177411//National Research Foundation of Korea/Korea ; HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; }, abstract = {Studies showing that coronavirus disease 2019 (COVID-19) is associated with an increased risk of cardiovascular disease continue to be published. However, studies on how long the overall cardiovascular risk increases after COVID-19 and the magnitude of its long-term effects have only been confirmed recently. This is partly because the distinction between cardiovascular risk as an acute complication of COVID-19 or post-acute cardiovascular manifestations is ambiguous. Long-COVID has arisen as an important topic in the second half of the pandemic. This term indicates that symptoms persist for more than two 2 months; following three months of SARS-CoV-2 infection and cannot be explained by other medical conditions. Despite the agreement of these international organizations and experts, it is difficult to define whether there is sufficient medical evidence to prove the existence of long-COVID. However, the Korean government and Korea Disease Control and Prevention Agency (KDCA) are preparing a new platform to assess the long-term impact of COVID-19. Using this data, a prospective cohort of 10,000 confirmed COVID-19 cases will be established. This cohort will be linked with claims data from the National Health Insurance Services (NHIS) and it is expected that increased real-world evidence of long-COVID will be accumulated.}, } @article {pmid36343181, year = {2022}, author = {Yonts, A Brugler and Burton, J and Jones Herbert, L}, title = {A Review of Current Evaluation and Management Strategies in Pediatric Postacute Sequelae of COVID-19.}, journal = {Pediatric annals}, volume = {51}, number = {11}, pages = {e421-e425}, doi = {10.3928/19382359-20220913-08}, pmid = {36343181}, issn = {1938-2359}, mesh = {Adolescent ; Child ; Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Disease Progression ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pediatric postacute sequelae of COVID-19 (pPASC), or long COVID, is a complex, heterogeneous, multisystem syndrome that leads to disruption in the lives of children and adolescents for months, and possibly years, after recovery from acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. While the underlying pathophysiologic mechanisms of PASC are still under investigation, clinicians are facing the immediate challenges of treating these patients. In this article, we provide an overview of the current multidisciplinary evaluation of patients with pPASC. We also offer guidance on the medical, psychological, and rehabilitative management strategies based on experience with both pPASC and patients with other postviral syndromes. [Pediatr Ann. 2022;51(11):e421-e425.].}, } @article {pmid36343180, year = {2022}, author = {Yonts, A Brugler}, title = {Pediatric Long-COVID: A Review of the Definition, Epidemiology, Presentation, and Pathophysiology.}, journal = {Pediatric annals}, volume = {51}, number = {11}, pages = {e416-e420}, doi = {10.3928/19382359-20220913-06}, pmid = {36343180}, issn = {1938-2359}, mesh = {Child ; Humans ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Activities of Daily Living ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although children have been largely spared the most severe consequences of acute infection with SARS-CoV-2 virus, it is estimated that up to one-quarter of the more than 14 million children diagnosed as having coronavirus disease 2019 (COVID-19) have developed persistent symptoms of fatigue, postexertional malaise, neurologic and cognitive symptoms, and other symptoms that interfere with activities of daily living for months after their initial illness. Pediatric postacute sequelae of COVID-19 (pPASC), or long-COVID, is a complex, heterogeneous, postviral condition involving multiple body systems and is likely attributable to several concurrent underlying physiologic processes, including damage from direct viral invasion, endovascular dysfunction and microthrombosis, viral persistence, and the development of autoimmunity. In this review, we explore the current state of the literature regarding definition, epidemiology, clinical presentation, and proposed pathophysiologic mechanisms of pPASC. [Pediatr Ann. 2022;51(11):e416-e420.].}, } @article {pmid36341457, year = {2022}, author = {Apostolou, E and Rizwan, M and Moustardas, P and Sjögren, P and Bertilson, BC and Bragée, B and Polo, O and Rosén, A}, title = {Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {949787}, pmid = {36341457}, issn = {1664-3224}, mesh = {Humans ; *Fatigue Syndrome, Chronic ; *COVID-19 ; Saliva ; SARS-CoV-2 ; *Herpesvirus 6, Human ; Antibodies, Viral ; *Endogenous Retroviruses ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.

METHODS: Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.

RESULTS: At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.

CONCLUSION: Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.}, } @article {pmid36341327, year = {2022}, author = {Kundura, L and Cezar, R and André, S and Campos-Mora, M and Lozano, C and Vincent, T and Muller, L and Lefrant, JY and Roger, C and Claret, PG and Duvnjak, S and Loubet, P and Sotto, A and Tran, TA and Estaquier, J and Corbeau, P}, title = {Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1029006}, pmid = {36341327}, issn = {1664-3224}, mesh = {Humans ; *COVID-19 ; Perforin/genetics ; SARS-CoV-2 ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; CD8-Positive T-Lymphocytes ; Post-Acute COVID-19 Syndrome ; }, abstract = {T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.}, } @article {pmid36339936, year = {2022}, author = {Struijk, M and Möller, T and Bruinvels, D and Spreeuwers, D}, title = {[Not Available].}, journal = {Tijdschrift voor bedrijfs- en verzekeringsgeneeskunde}, volume = {30}, number = {7-8}, pages = {40-43}, doi = {10.1007/s12498-022-2026-1}, pmid = {36339936}, issn = {1876-5858}, } @article {pmid36339677, year = {2022}, author = {Amekran, Y and Damoun, N and El Hangouche, AJ}, title = {Postural orthostatic tachycardia syndrome and post-acute COVID-19.}, journal = {Global cardiology science & practice}, volume = {2022}, number = {1-2}, pages = {e202213}, pmid = {36339677}, issn = {2305-7823}, abstract = {While the acute illness of COVID-19 was the initial focus of concern, there are increasing reports of patients with chronic symptoms, known as long-COVID. Dysautonomia may be a possible post-acute neurological complication explaining the persistent symptoms observed in long COVID. Postural tachycardia syndrome (POTS), a form of dysautonomia characterized by sustained tachycardia and orthostatic intolerance, has been increasingly reported in patients after SARS-CoV-2 infection. In this context, this review aimed to report and discuss the available literature pertaining to post COVID-19 POTS.}, } @article {pmid36339175, year = {2022}, author = {Moens, M and Duarte, RV and De Smedt, A and Putman, K and Callens, J and Billot, M and Roulaud, M and Rigoard, P and Goudman, L}, title = {Health-related quality of life in persons post-COVID-19 infection in comparison to normative controls and chronic pain patients.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {991572}, pmid = {36339175}, issn = {2296-2565}, mesh = {Humans ; *Chronic Pain/epidemiology ; *COVID-19/epidemiology ; Pandemics ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: The Coronavirus disease 2019 (COVID-19) pandemic exerted a tremendous pressure on the healthcare system, people's social life, mental health and financial status with profound implications for the general population. The exact impact of the pandemic on the overall physical, mental and social wellbeing of COVID-19 infection survivors on the long term has not yet been explored in a thorough way. Based on the reporting of persistent pain, fatigue and dyspnea symptoms by these survivors, it is our hypothesis that their quality of life will be extremely impacted, as is observed in patients with chronic pain. Therefore, the first aim of this study was to perform an in-depth evaluation of the quality of life of post-COVID-19 infected persons. The second aim was to compare the quality of life of these persons with a normative population and with patients with chronic pain. Health-related quality of life, as a measure for a person's overall physical, mental, and social wellbeing, was measured with the 3-level EQ5D in 547 post-COVID-19 infected persons. These data were compared to reference data from normal population records for Belgium and to data from patients with chronic pain after spinal surgery with two-way analyses of variance. In total, 89.58% of the post-COVID-19 infected persons reported pain/discomfort and 82.45% indicated limitations when performing usual activities, when evaluated 287 days (SD: 150) after the infection. Self-care was preserved in most post-COVID-19 persons, whereby only 13.16% indicated problems. The mean EQ5D-3L index score was 0.57 (SD: 0.23) and EQ5D VAS mean score was 56.6 (SD: 18.2). The mean index score for the normative population was significantly higher than for COVID-19 infected persons [mean difference of 0.31 (95% from 0.29 to 0.33), p < 0.01] while the mean score of chronic pain patients was significantly lower than the score of COVID-19 infected persons [mean difference of -0.31 (95% from -0.29 to -0.33), p < 0.01]. Compared to age-and sex adjusted reference data, health-related quality of life of persons with long COVID is severely impacted. In relation to patients with chronic pain after spinal surgery, the quality of life of post-COVID-19 infected persons seemed to be better.

CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov/, identifier: NCT04912778.}, } @article {pmid36338320, year = {2023}, author = {Machado, K and Ayuk, P}, title = {Post-COVID-19 condition and pregnancy.}, journal = {Case reports in women's health}, volume = {37}, number = {}, pages = {e00458}, pmid = {36338320}, issn = {2214-9112}, } @article {pmid36337508, year = {2022}, author = {Engelmann, P and Löwe, B and Brehm, TT and Weigel, A and Ullrich, F and Addo, MM and Schulze Zur Wiesch, J and Lohse, AW and Toussaint, A}, title = {Risk factors for worsening of somatic symptom burden in a prospective cohort during the COVID-19 pandemic.}, journal = {Frontiers in psychology}, volume = {13}, number = {}, pages = {1022203}, pmid = {36337508}, issn = {1664-1078}, abstract = {INTRODUCTION: Little is known about risk factors for both Long COVID and somatic symptoms that develop in individuals without a history of COVID-19 in response to the pandemic. There is reason to assume an interplay between pathophysiological mechanisms and psychosocial factors in the etiology of symptom persistence.

OBJECTIVE: Therefore, this study investigates specific risk factors for somatic symptom deterioration in a cohort of German adults with and without prior SARS-CoV-2 infection.

METHODS: German healthcare professionals underwent SARS-CoV-2 IgG antibody testing and completed self-rating questionnaires at baseline and 21 months later between April 2020 and February 2022. Differences in variables between the time points were analyzed and a regression analysis was performed to predict somatic symptom deterioration at follow-up.

RESULTS: Seven hundred fifty-one adults completed both assessments. Until follow-up, n = 58 had contracted SARS-CoV-2 confirmed by serology. Between baseline and follow-up, signs of mental and physical strain increased significantly in the sample. Symptom expectations associated with COVID-19 and a self-reported history of COVID-19, but not serologically confirmed SARS-CoV-2 infection, significantly predicted somatic symptom deterioration at follow-up. A further predictor was baseline psychological symptom burden.

CONCLUSIONS: This study supports a disease-overarching biopsychosocial model for the development of burdensome somatic symptoms during the COVID-19 pandemic and supports research findings that symptom burden may be more related to the psychosocial effects of the pandemic than to infection itself. Future studies on Long COVID should include SARS-CoV-2 negative control groups and consider symptom burden prior to infection in order to avoid an overestimation of prevalence rates.}, } @article {pmid36337133, year = {2022}, author = {Denning, J and Parks, H}, title = {Trying times: an experience of early pandemic COVID-19 diagnosis and enduring long COVID.}, journal = {Breathe (Sheffield, England)}, volume = {18}, number = {2}, pages = {220061}, doi = {10.1183/20734735.0061-2022}, pmid = {36337133}, issn = {1810-6838}, abstract = {COVID-19 has affected us all, but for those with long COVID there is a need for patience and compassion as we learn to treat this emerging condition. https://bit.ly/3A7JCpZ.}, } @article {pmid36337005, year = {2023}, author = {Juhász, V and Szabó, L and Pavlik, A and Tállay, A and Balla, D and Kiss, O and Babity, M and Sydó, N and Csulak, E and Benczúr, A and Országh, A and Gregor, Z and Becker, D and Merkely, B and Vágó, H}, title = {Short and mid-term characteristics of COVID-19 disease course in athletes: A high-volume, single-center study.}, journal = {Scandinavian journal of medicine & science in sports}, volume = {33}, number = {3}, pages = {341-352}, pmid = {36337005}, issn = {1600-0838}, support = {2020-4.1.1.-TKP2020//Ministry for Innovation and Technology in Hungary, Thematic Excellence Programme/ ; NVKP_16-1-2016-0017//National Research, Development, and Innovation Fund of Hungary/ ; RRF-2.3.1-21-2022-00004//European Union/ ; 2020-1.1.6-JÖVŐ-2021-00013//National Research, Development and Innovation Office of Hungary/ ; }, mesh = {Humans ; Male ; Female ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Myocardium ; Athletes ; }, abstract = {INTRODUCTION: At the pandemic's beginning, significant concern has risen about the prevalence of myocardial involvement after SARS-CoV-2 infection. We assessed the cardiovascular burden of SARS-CoV-2 in a large cohort of athletes and identified factors that might affect the disease course. We included 633 athletes in our study on whom we performed extensive cardiology examinations after recovering from SARS-CoV-2 infection. More than half of the athletes (n = 322) returned for a follow-up examination median of 107 days after the commencement of their infection.

RESULTS: Troponin T positivity was as low as 1.4% of the athletes, where the subsequently performed examinations did not show definitive, ongoing myocardial injury. Altogether, 31% of the athletes' rapid training rebuild was hindered by persistent or reoccurring symptoms. Female athletes reported a higher prevalence of return to play (RTP) symptoms than their male counterparts (34% vs. 19%, p = 0.005). The development of long COVID symptoms was independently predicted by increasing age and acute symptoms' severity in a multiple regression model (AUC 0.75, CI 0.685-0.801). Athletes presenting with either or both cough and ferritin levels higher than >150 μg/L had a 4.1x (CI 1.78-9.6, p = 0.001) higher odds ratio of developing persistent symptoms.

CONCLUSION: While SARS-CoV-2 rarely affects the myocardium in athletes, about one in three of them experience symptoms beyond the acute phase. Identifying those athletes with a predisposition to developing long-standing symptoms may aid clinicians and trainers in finding the optimal return-to-play timing and training load rebuild pace.}, } @article {pmid36330986, year = {2022}, author = {MohanaSundaram, A and Sathanantham, ST and Velayutham, R}, title = {Long COVID-19 and used cooking oil consumption in India: The potential for concurrent and cascading scourges - Correspondence.}, journal = {International journal of surgery (London, England)}, volume = {107}, number = {}, pages = {106972}, pmid = {36330986}, issn = {1743-9159}, mesh = {Humans ; *COVID-19/epidemiology ; Cooking ; India/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36327888, year = {2022}, author = {Dobie, T}, title = {Neuro-immune interactions: The spectacular forest.}, journal = {Neuron}, volume = {110}, number = {21}, pages = {3407-3408}, doi = {10.1016/j.neuron.2022.10.023}, pmid = {36327888}, issn = {1097-4199}, mesh = {Humans ; *COVID-19 ; Ecosystem ; Neuroimmunomodulation ; Forests ; Post-Acute COVID-19 Syndrome ; }, abstract = {In this special issue of Neuron, we present a series of opinions and reviews on neuro-immune interactions. Recent insights into how profoundly the nervous and immune systems affect each other, bolstered by trans-disciplinary collaboration, have revolutionized both neuroscience and immunology. Like a forest ecosystem, an organism thrives or withers depending on the balance of its components. Highlighted in this special issue is a small sampling of the ever-growing list of diseases influenced by dysfunctional neuro-immune crosstalk, ranging from multiple sclerosis and brain cancer to long COVID and Alzheimer's.}, } @article {pmid36326761, year = {2022}, author = {O'Hare, AM and Vig, EK and Iwashyna, TJ and Fox, A and Taylor, JS and Viglianti, EM and Butler, CR and Vranas, KC and Helfand, M and Tuepker, A and Nugent, SM and Winchell, KA and Laundry, RJ and Bowling, CB and Hynes, DM and Maciejewski, ML and Bohnert, ASB and Locke, ER and Boyko, EJ and Ioannou, GN and , }, title = {Complexity and Challenges of the Clinical Diagnosis and Management of Long COVID.}, journal = {JAMA network open}, volume = {5}, number = {11}, pages = {e2240332}, pmid = {36326761}, issn = {2574-3805}, support = {IK2 HX003005/HX/HSRD VA/United States ; IK6 HX003395/HX/HSRD VA/United States ; K23 DK129777/DK/NIDDK NIH HHS/United States ; }, mesh = {Male ; Humans ; Middle Aged ; Female ; *COVID-19/diagnosis/epidemiology ; SARS-CoV-2 ; Clinical Decision-Making ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: There is increasing recognition of the long-term health effects of SARS-CoV-2 infection (sometimes called long COVID). However, little is yet known about the clinical diagnosis and management of long COVID within health systems.

OBJECTIVE: To describe dominant themes pertaining to the clinical diagnosis and management of long COVID in the electronic health records (EHRs) of patients with a diagnostic code for this condition (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code U09.9).

This qualitative analysis used data from EHRs of a national random sample of 200 patients receiving care in the Department of Veterans Affairs (VA) with documentation of a positive result on a polymerase chain reaction (PCR) test for SARS-CoV-2 between February 27, 2020, and December 31, 2021, and an ICD-10 diagnostic code for long COVID between October 1, 2021, when the code was implemented, and March 1, 2022. Data were analyzed from February 5 to May 31, 2022.

MAIN OUTCOMES AND MEASURES: A text word search and qualitative analysis of patients' VA-wide EHRs was performed to identify dominant themes pertaining to the clinical diagnosis and management of long COVID.

RESULTS: In this qualitative analysis of documentation in the VA-wide EHR, the mean (SD) age of the 200 sampled patients at the time of their first positive PCR test result for SARS-CoV-2 in VA records was 60 (14.5) years. The sample included 173 (86.5%) men; 45 individuals (22.5%) were identified as Black and 136 individuals (68.0%) were identified as White. In qualitative analysis of documentation pertaining to long COVID in patients' EHRs 2 dominant themes were identified: (1) clinical uncertainty, in that it was often unclear whether particular symptoms could be attributed to long COVID, given the medical complexity and functional limitations of many patients and absence of specific markers for this condition, which could lead to ongoing monitoring, diagnostic testing, and specialist referral; and (2) care fragmentation, describing how post-COVID-19 care processes were often siloed from and poorly coordinated with other aspects of care and could be burdensome to patients.

CONCLUSIONS AND RELEVANCE: This qualitative study of documentation in the VA EHR highlights the complexity of diagnosing long COVID in clinical settings and the challenges of caring for patients who have or are suspected of having this condition.}, } @article {pmid36326730, year = {2022}, author = {Kessler, A and Heightman, M and Brennan, E}, title = {Post-COVID-19 respiratory problems: burden and management.}, journal = {Current opinion in supportive and palliative care}, volume = {16}, number = {4}, pages = {203-209}, doi = {10.1097/SPC.0000000000000619}, pmid = {36326730}, issn = {1751-4266}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Quality of Life ; Respiratory Function Tests ; *Lung Diseases, Interstitial ; Lung ; }, abstract = {PURPOSE OF REVIEW: To describe the burden of post-COVID respiratory sequelae in posthospital and nonhospitalized COVID-19 survivors and to describe the priorities of clinical management.

RECENT FINDINGS: Due to varying definitions of 'Long COVID' or 'Post-COVID', the prevalence of post-COVID sequelae or persisting symptoms is challenging to estimate but ranges from 2.3 to 51%. Risk factors for persistent post-COVID symptoms include age, female sex, deprivation, presence of comorbidities; and in posthospital COVID-19 survivors, the severity of acute infection. Common post-COVID respiratory symptoms include breathlessness, cough and chest pain and many individuals also experience exercise intolerance. The most common pulmonary function test abnormality is impaired diffusing capacity for carbon monoxide. In posthospital COVID-19 survivors, the prevalence of interstitial lung damage is 5-11%. Disordered breathing is common in all post-COVID patients and respiratory physiotherapy is helpful.

SUMMARY: The vast numbers of COVID-19 infections globally implies that a large number of people will be affected by post-COVID sequelae even with conservative estimates. A significant number of people are affected for several months and up to years following acute infection. Post-COVID sequelae have a detrimental impact on quality of life and ability to work.}, } @article {pmid36326545, year = {2022}, author = {Zawilska, JB and Kuczyńska, K}, title = {Psychiatric and neurological complications of long COVID.}, journal = {Journal of psychiatric research}, volume = {156}, number = {}, pages = {349-360}, pmid = {36326545}, issn = {1879-1379}, mesh = {Child ; Humans ; Adolescent ; *Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; }, abstract = {COVID-19 was primarily considered a pulmonary disease with extrapulmonary manifestations. As the pandemic spread, there has been growing evidence that the disease affects various organs/systems, including the central and peripheral nervous systems. Accumulation of clinical data demonstrates that in a large population of survivors impairments in the function of one or more organs may persist for a long time, a phenomenon commonly known as post COVID or long COVID. Fatigue and cognitive dysfunction, such as concentration problems, short-term memory deficits, general memory loss, a specific decline in attention, language and praxis abilities, encoding and verbal fluency, impairment of executive functions, and psychomotor coordination, are amongst the most common and debilitating features of neuropsychatric symptoms of post COVID syndrome. Several patients also suffer from compromised sleep, depression, anxiety and post-traumatic stress disorder. Patients with long COVID may demonstrate brain hypometabolism, hypoperfusion of the cerebral cortex and changes in the brain structure and functional connectivity. Children and adolescents represent a minority of COVID-19 cases, so not surprisingly data on the long-term sequelae after SARS-CoV-2 infections in these age groups are scarce. Although the pathogenesis, clinical characteristics, epidemiology, and risk factors of the acute phase of COVID-19 have been largely explained, these areas are yet to be explored in long COVID. This review aims to provide an update on what is currently known about long COVID effects on mental health.}, } @article {pmid36324612, year = {2022}, author = {Efstathiou, V and Stefanou, MI and Demetriou, M and Siafakas, N and Katsantoni, E and Makris, M and Tsivgoulis, G and Zoumpourlis, V and Kympouropoulos, SP and Tsoporis, JN and Spandidos, DA and Ferentinos, P and Smyrnis, N and Rizos, E}, title = {New‑onset neuropsychiatric sequelae and 'long‑COVID' syndrome (Review).}, journal = {Experimental and therapeutic medicine}, volume = {24}, number = {5}, pages = {705}, pmid = {36324612}, issn = {1792-1015}, abstract = {The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships.}, } @article {pmid36324314, year = {2022}, author = {Suba Rao, HR and Hamzaid, NA and Ahmad, MY and Hamzah, N}, title = {Physiological factors affecting the mechanical performance of peripheral muscles: A perspective for long COVID patients through a systematic literature review.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {958333}, pmid = {36324314}, issn = {1664-042X}, abstract = {Background: Peripheral muscle weakness can be measured quantitatively in long COVID patients. Mechanomyography (MMG) is an alternative tool to measure muscle strength non-invasively. Objective: This literature review aims to provide evidence on the efficacy of MMG in measuring muscle strength for long COVID patients and to determine the physiological factors that may affect the use of MMG in assessing muscle performance. Methods: A systematic literature review was conducted using EBSCO's MEDLINE Complete. A total of five out of 2,249 potential publications fulfilled the inclusion criteria. Results: The selected studies addressed muscle performance based on the physiological effects of age, gender, and physical activity level. MMG is sensitive in measuring muscle strength for long COVID patients due to its higher signal-to-noise ratio and lightweight accelerometers. Its neglectable skin impedance and low risk of influences during the recording of surface motions make MMG a reliable tool. Conclusion: Muscle performance is affected by age, gender, and physical activity level. Sensors, such as MMG, as well as the length of the muscle and the characteristics of the muscle activity, are important considerations when choosing a sensor for diagnostic evaluation. The efficacy of MMG in measuring muscle strength for long COVID patients and the physiological factors that may affect the use of MMG in assessing muscle performance are discussed.}, } @article {pmid36324055, year = {2023}, author = {Hallmann, E and Sikora, D and Poniedziałek, B and Szymański, K and Kondratiuk, K and Żurawski, J and Brydak, L and Rzymski, P}, title = {IgG autoantibodies against ACE2 in SARS-CoV-2 infected patients.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28273}, pmid = {36324055}, issn = {1096-9071}, mesh = {Male ; Humans ; Female ; SARS-CoV-2 ; *COVID-19 ; Angiotensin-Converting Enzyme 2 ; Peptidyl-Dipeptidase A/metabolism ; *Influenza, Human ; Post-Acute COVID-19 Syndrome ; Immunoglobulin G ; Autoantibodies ; }, abstract = {How frequently autoantibodies against angiotensin-converting enzyme 2 (ACE2) occur in patients infected by SARS-CoV-2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long-lasting effects of COVID-19 observed in some individuals, particularly if IgG-class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS-CoV-2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti-ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID-19, but some severe and asymptomatic cases were also observed. Patients with severe infection had twofold higher titers than mild and asymptomatic cases. Age, comorbidities, and influenza vaccination status were not related to antibody prevalence. The prevalence of IgG anti-SARS-CoV-2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor-binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS-CoV-2 infection, particularly concerning long COVID-19.}, } @article {pmid36323892, year = {2022}, author = {Graham, F}, title = {Daily briefing: The crushing 'brain fog' of long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-02969-1}, pmid = {36323892}, issn = {1476-4687}, } @article {pmid36323462, year = {2022}, author = {Kjellberg, A and Abdel-Halim, L and Hassler, A and El Gharbi, S and Al-Ezerjawi, S and Boström, E and Sundberg, CJ and Pernow, J and Medson, K and Kowalski, JH and Rodriguez-Wallberg, KA and Zheng, X and Catrina, S and Runold, M and Ståhlberg, M and Bruchfeld, J and Nygren-Bonnier, M and Lindholm, P}, title = {Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial.}, journal = {BMJ open}, volume = {12}, number = {11}, pages = {e061870}, pmid = {36323462}, issn = {2044-6055}, mesh = {Humans ; Clinical Trials, Phase II as Topic ; *COVID-19/therapy ; Double-Blind Method ; *Hyperbaric Oxygenation ; Prospective Studies ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.

METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.

ETHICS AND DISSEMINATION: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.

TRIAL REGISTRATION NUMBER: NCT04842448.}, } @article {pmid36323438, year = {2023}, author = {Winkelmann, S and Korth, A and Voss, B and Nasr, MA and Behrend, N and Pudszuhn, A and Hofmann, VM and Schendzielorz, P and Maetzler, C and Hermes, A and Borzikowsky, C and Bahmer, T and Lieb, W and Schreiber, S and Stork, S and Montellano, FA and Witzenrath, M and Keil, T and Krawczak, M and Laudien, M and On Behalf Of The Napkon Study Group, NSG}, title = {Persisting chemosensory dysfunction in COVID-19 - a cross-sectional population-based survey.}, journal = {Rhinology}, volume = {61}, number = {1}, pages = {12-23}, doi = {10.4193/Rhin22.176}, pmid = {36323438}, issn = {0300-0729}, mesh = {Adult ; Humans ; Middle Aged ; *COVID-19 ; Cross-Sectional Studies ; *Olfaction Disorders/epidemiology/etiology/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Smell ; Taste Disorders/epidemiology/etiology ; }, abstract = {BACKGROUND: Chemosensory dysfunction (CD) has been reported as a common symptom of SARS-CoV-2 infection, but it is not well understood whether and for how long changes of smell, taste and chemesthesis persist in infected individuals.

METHODOLOGY: Unselected adult residents of the German federal state of Schleswig-Holstein with Polymerase Chain Reaction (PCR)-test-confirmed SARS-CoV-2 infection were invited to participate in this large cross-sectional study. Data on the medical history and subjective chemosensory function of participants were obtained through questionnaires and visual analogue scales (VAS). Olfactory function (OF) was objectified with the Sniffin Sticks test (SST), including threshold (T), discrimination (D) and identification (I) test as well as summarized TDI score, and compared to that in healthy controls. Gustatory function (GF) was evaluated with the suprathreshold taste strips (TS) test, and trigeminal function was tested with an ampoule containing ammonia.

RESULTS: Between November 2020 and June 2021, 667 infected individuals (mean age: 48.2 years) were examined 9.1 months, on average, after positive PCR testing. Of these, 45.6% had persisting subjective olfactory dysfunction (OD), 36.2% had subjective gustatory dysfunction (GD). Tested OD, tested GD and impaired trigeminal function were observed in 34.6%, 7.3% and 1.8% of participants, respectively. The mean TDI score of participants was significantly lower compared to healthy subjects. Significant associations were observed between subjective OD and GD, and between tested OD and GD.

CONCLUSION: Nine months after SARS-CoV-2 infection, OD prevalence is significantly increased among infected members of the general population. Therefore, OD should be included in the list of symptoms collectively defining Long-COVID.}, } @article {pmid36322364, year = {2022}, author = {Mohammad, KO and Lin, A and Rodriguez, JBC}, title = {Cardiac Manifestations of Post-Acute COVID-19 Infection.}, journal = {Current cardiology reports}, volume = {24}, number = {12}, pages = {1775-1783}, pmid = {36322364}, issn = {1534-3170}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Heart ; Arrhythmias, Cardiac ; }, abstract = {PURPOSE OF REVIEW: There is emerging evidence that the post-acute and chronic phases of COVID-19 infection are associated with various significant cardiovascular sequelae.

RECENT FINDINGS: Long COVID has been shown to be associated with multiple cardiovascular sequelae including direct myocardial injury, arrhythmias, and cardiomyopathies. Hypotheses on the mechanism of myocardial injury include direct viral infiltration and autoimmune dysregulation. Long COVID is associated with persistent cardiac ischemia in patients with no previous history of coronary disease, atrial and ventricular arrhythmias, and the development of new-onset heart failure in previously healthy patients. Onset of long COVID may be related to severity of the initial SARS-CoV2 infection. Cardiac MRI is a valuable tool in assessing myocarditis and the development of cardiomyopathies in the setting of long COVID. Both patients with and without pre-existing cardiovascular disease are at risk of developing myocardial injury in the setting of long COVID. Future studies will elucidate both cardiovascular mortality and cardiac rehabilitation in the post-acute and chronic phases of COVID-19.}, } @article {pmid36322190, year = {2023}, author = {Goehringer, F and Bruyere, A and Doyen, M and Bevilacqua, S and Charmillon, A and Heyer, S and Verger, A}, title = {Brain [18]F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {50}, number = {4}, pages = {1084-1089}, pmid = {36322190}, issn = {1619-7089}, mesh = {Humans ; *Fluorodeoxyglucose F18/metabolism ; Retrospective Studies ; Outpatients ; Asthenia/metabolism ; Positron-Emission Tomography/methods ; *COVID-19/diagnostic imaging ; Brain/diagnostic imaging/metabolism ; }, abstract = {BACKGROUND: Brain [18]F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain [18]F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics.

METHODS: We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain [18]F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics.

RESULTS: Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection (r =  - 0.44, p = 0.02) and with the duration of symptoms (r =  - 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase (p ≤ 0.04) were associated with these hypometabolic clusters.

CONCLUSION: Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement.}, } @article {pmid36319840, year = {2022}, author = {Di Gennaro, L and Valentini, P and Sorrentino, S and Ferretti, MA and De Candia, E and Basso, M and Lancellotti, S and De Cristofaro, R and De Rose, C and Mariani, F and Morello, R and Lazzareschi, I and Sigfrid, L and Munblit, D and Buonsenso, D}, title = {Extended coagulation profile of children with Long Covid: a prospective study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18392}, pmid = {36319840}, issn = {2045-2322}, support = {65925795//pfizer non competitive grant/ ; }, mesh = {Adult ; Female ; Humans ; Child ; Infant, Newborn ; Male ; *COVID-19 ; von Willebrand Factor ; Prospective Studies ; SARS-CoV-2 ; Case-Control Studies ; COVID-19 Testing ; Fibrinogen/analysis ; Post-Acute COVID-19 Syndrome ; }, abstract = {Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8-12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.}, } @article {pmid36319780, year = {2023}, author = {Al-Aly, Z and Agarwal, A and Alwan, N and Luyckx, VA}, title = {Long COVID: long-term health outcomes and implications for policy and research.}, journal = {Nature reviews. Nephrology}, volume = {19}, number = {1}, pages = {1-2}, pmid = {36319780}, issn = {1759-507X}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Policy ; Outcome Assessment, Health Care ; Long-Term Care ; }, abstract = {Long COVID, which refers to post-acute and chronic sequelae of SARS-CoV-2 infection, can affect nearly every organ system and all demographic groups. The high and growing toll of long COVID calls for an urgent need to understand how to prevent and treat it. Governments and health systems must address the care needs of people with long COVID.}, } @article {pmid36319681, year = {2022}, author = {Heubner, L and Petrick, PL and Güldner, A and Bartels, L and Ragaller, M and Mirus, M and Rand, A and Tiebel, O and Beyer-Westendorf, J and Rößler, M and Schmitt, J and Koch, T and Spieth, PM}, title = {Extreme obesity is a strong predictor for in-hospital mortality and the prevalence of long-COVID in severe COVID-19 patients with acute respiratory distress syndrome.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18418}, pmid = {36319681}, issn = {2045-2322}, mesh = {Aged ; Humans ; Male ; *COVID-19 ; Hospital Mortality ; Intensive Care Units ; Obesity ; Prevalence ; Respiration, Artificial ; *Respiratory Distress Syndrome ; Retrospective Studies ; Female ; Adult ; Middle Aged ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; }, abstract = {Acute Respiratory Distress Syndrome (ARDS) is common in COVID-19 patients and is associated with high mortality. The aim of this observational study was to describe patients' characteristics and outcome, identifying potential risk factors for in-hospital mortality and for developing Long-COVID symptoms. This retrospective study included all patients with COVID-19 associated ARDS (cARDS) in the period from March 2020 to March 2021 who were invasively ventilated at the intensive care unit (ICU) of the University Hospital Dresden, Germany. Between October 2021 and December 2021 patients discharged alive (at minimum 6 months after hospital discharge-midterm survival) were contacted and interviewed about persistent symptoms possibly associated with COVID-19 as well as the quality of their lives using the EQ-5D-5L-questionnaire. Long-COVID was defined as the occurrence of one of the symptoms at least 6 months after discharge. Risk factors for mortality were assessed with Cox regression models and risk factors for developing Long-COVID symptoms by using relative risk (RR) regression. 184 Patients were included in this study (male: n = 134 (73%), median age 67 (range 25-92). All patients were diagnosed with ARDS according to the Berlin Definition. 89% of patients (n = 164) had severe ARDS (Horovitz-index < 100 mmHg). In 27% (n = 49) extracorporeal membrane oxygenation was necessary to maintain gas exchange. The median length of in-hospital stay was 19 days (range 1-60). ICU mortality was 51%, hospital mortality 59%. Midterm survival (median 11 months) was 83% (n = 55) and 78% (n = 43) of these patients presented Long-COVID symptoms with fatigue as the most common symptom (70%). Extreme obesity (BMI > 40 kg/m[2]) was the strongest predictor for in-hospital mortality (hazard ratio: 3.147, confidence interval 1.000-9.897) and for developing Long-COVID symptoms (RR 1.61, confidence interval 1.26-2.06). In-hospital mortality in severe cARDS patients was high, but > 80% of patients discharged alive survived the midterm observation period. Nonetheless, most patients developed Long-COVID symptoms. Extreme obesity with BMI > 40 kg/m[2] was identified as independent risk factor for in-hospital mortality and for developing Long-COVID symptoms.Trial registration DRKS-ID DRKS00027856.}, } @article {pmid36319644, year = {2022}, author = {Hastie, CE and Lowe, DJ and McAuley, A and Winter, AJ and Mills, NL and Black, C and Scott, JT and O'Donnell, CA and Blane, DN and Browne, S and Ibbotson, TR and Pell, JP}, title = {Author Correction: Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6540}, doi = {10.1038/s41467-022-34344-z}, pmid = {36319644}, issn = {2041-1723}, support = {CH/F/21/90010/BHF_/British Heart Foundation/United Kingdom ; }, } @article {pmid36317311, year = {2023}, author = {Kaushik, P and Kumari, M and Singh, NK and Suri, A}, title = {The role of gut microbiota in etiopathogenesis of long COVID syndrome.}, journal = {Hormone molecular biology and clinical investigation}, volume = {44}, number = {2}, pages = {113-114}, pmid = {36317311}, issn = {1868-1891}, mesh = {Humans ; *Gastrointestinal Microbiome ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Probiotics ; Prebiotics ; }, } @article {pmid36317108, year = {2022}, author = {Thewjitcharoen, Y and Krittiyawong, S and Nakasatien, S and Himathongkam, T}, title = {Kratom-Associated Mixed Cholestatic-Hepatocellular Liver Injury in a Patient With Long COVID: A case Report.}, journal = {Clinical medicine insights. Case reports}, volume = {15}, number = {}, pages = {11795476221132824}, pmid = {36317108}, issn = {1179-5476}, abstract = {INTRODUCTION: Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom which led people in many areas to seek income from the sale of kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-COVID syndrome who developed a mixed cholestatic-hepatocellular liver injury secondary to kratom.

CASE PRESENTATION: A 23-year-old Thai man was seen for an evaluation of fatigue and nausea which was soon followed by pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was purchased from a friend and used in a homemade iced cocktail called "4 × 100" consisting of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. His lab workup showed his total bilirubin to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, and alanine aminotransferase was 1635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed normal liver and no cirrhosis. The case was managed conservatively for 5 days in the hospital by giving intravenous fluid and stopping all medications. Urine toxicology screening confirmed the presence of mitragynine and diphenhydramine. He was in a stable condition with normalized liver function tests at 3 months after discharge.

CONCLUSION: The COVID-19 pandemic has posed unprecedented challenges to health consequences and this case highlights the importance of kratom as potential cause of acute liver injury. Future studies should accumulate further case series and identify kratom-user subgroups or the polydrug patterns of kratom use that are at heightened risk of severe liver injury.}, } @article {pmid36317068, year = {2022}, author = {Tarantino, U and Visconti, VV and Bonanni, R and Gatti, A and Marcozzi, M and Calabrò, D and Cariati, I}, title = {Osteosarcopenia and Long-COVID: a dangerous combination.}, journal = {Therapeutic advances in musculoskeletal disease}, volume = {14}, number = {}, pages = {1759720X221130485}, pmid = {36317068}, issn = {1759-720X}, abstract = {SARS-CoV-2 has caused a global pandemic and an unprecedented public health crisis, infecting more than 580 million people worldwide. Moreover, recent evidence has suggested the emergence of a new syndrome known as Long-COVID, a term used to describe a diverse set of physical and mental symptoms that persist after a diagnosed SARS-CoV-2 infection. Epidemiological data have identified myalgias, muscle and joint dysfunction, and bone fragility as common sequelae in patients with moderate and severe forms of this disease. Significant musculoskeletal dysfunction has also been detected in some healed patients, although knowledge about pathophysiological mechanisms of Long-COVID is still rather scarce. In this context, SARS-CoV-2 infection has been suggested to amplify the effects of aging on the musculoskeletal system by aggravating the osteosarcopenic state. Based on this evidence, our review focused on the muscle and bone tissue alterations induced by SARS-CoV-2 infection and Long-COVID, summarizing the current knowledge on the underlying biological mechanisms and highlighting the need for a multidisciplinary approach to predict the musculoskeletal targets and long-term consequences of COVID-19 disease.}, } @article {pmid36316955, year = {2023}, author = {Dias, MB and Medeiros, APV and de Melo, SS and Fonseca, CS and Jacob-Filho, W and Avelino-Silva, TJ and Aliberti, MJR and , }, title = {The long and winding road of COVID-19 in survivors of hospitalisation: Symptoms trajectory and predictors of long COVID.}, journal = {Journal of internal medicine}, volume = {293}, number = {2}, pages = {264-268}, pmid = {36316955}, issn = {1365-2796}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Hospitalization ; Survivors ; }, } @article {pmid36316848, year = {2022}, author = {Luo, D and Liu, B and Wang, P and Liao, H and Mao, S and Chen, H and Huang, Y and Liu, L and Lan, W and Liu, F}, title = {Traditional Chinese medicine combined with Moxibustion in the treatment of "long-COVID": A protocol for systematic review and meta-analysis.}, journal = {Medicine}, volume = {101}, number = {43}, pages = {e31447}, pmid = {36316848}, issn = {1536-5964}, mesh = {Humans ; *Moxibustion/methods ; Medicine, Chinese Traditional/methods ; *COVID-19/therapy ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Research Design ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: From the end of 2019 to now, COVID-19 is still prevalent, which poses a great threat to international public health. With the increasing number of people infected, the number of patients with COVID-19 sequelae is also increasing, but there is no specific drug for COVID-19 sequelae. In China, traditional Chinese medicine combined with acupuncture has been widely used in COVID-19 sequelae, but there is still a lack of evidence-based medicine evaluation. The purpose of this study was to evaluate the efficacy and safety of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae.

METHODS: According to the retrieval strategy, the "long COVID" randomized controlled trial of traditional Chinese medicine combined with moxibustion will be search in eight databases composed of PubMed, Embase, Web of Science, China National knowledge Infrastructure Database, China Biomedical Database and China Science and Technology Journal Database, regardless of publication date or language. The study was screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the study. Meta-analysis was carried out using RevMan5.3 and STATA12.0 software. Finally, the level of evidence of the results will be evaluated.

RESULTS: This study will evaluate whether traditional Chinese medicine combined with moxibustion can effectively treat the symptoms of COVID-19 sequelae.

CONCLUSION: This study will provide evidence whether there is benefit of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. At the same time, our research results will provide a reference for clinical decision-making and guiding development in the future.}, } @article {pmid36316598, year = {2023}, author = {Hany, M and Zidan, A and Gaballa, M and Ibrahim, M and Agayby, ASS and Abouelnasr, AA and Sheta, E and Torensma, B}, title = {Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery.}, journal = {Obesity surgery}, volume = {33}, number = {1}, pages = {139-148}, pmid = {36316598}, issn = {1708-0428}, mesh = {Female ; Humans ; Adult ; Middle Aged ; Male ; *COVID-19 ; SARS-CoV-2 ; Gallbladder/surgery ; *Obesity, Morbid/surgery ; Stomach/surgery ; *Bariatric Surgery ; }, abstract = {BACKGROUND: Lingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gut tissue might be a source of infection during bariatric surgery. This study aimed to confirm the presence of SARS-CoV-2 nucleocapsid in gastric and gallbladder tissues removed during bariatric surgery in individuals previously infected with coronavirus disease 2019 (COVID-19) who had negative polymerase chain reaction results prior to the surgery.

METHODS: Gastric and gallbladder specimens from 80 patients who underwent bariatric surgery between November 2021 and May 2022 and had a history of COVID-19 infection with gastrointestinal symptoms were examined for the presence of lingering SARS-CoV-2 nucleocapsid proteins using immunohistochemistry.

RESULTS: Gastric specimens from 26 (32.5%) patients and 4 (100%) cholecystectomy specimens showed positive cytoplasmic staining for the anti-SARS-CoV-2 nucleocapsid protein in surface mucosal epithelial cells. The mean age was 37.8 ± 10.3 years. The average body mass index was 44.2 ± 7.0 kg/m[2]; most of the patients were females (71.3%). The positive staining group was significantly younger than the negative staining group (p = 0.007). The full-dose vaccination rate was 58.8%, with a median of 91 days after the last vaccine dose. A positive serological anti-spike IgG response was observed in 99% of the patients. The median time between initial COVID-19 infection and surgery was 274 and 380 days in the positive and negative staining groups, respectively (p = 0.371).

CONCLUSION: Gastric and gallbladder tissues can retain SARS-CoV-2 particles for a long time after COVID-19 infection, handling stomach specimens from patients during an operation must be done with care, as we usually do, but now with the knowledge that in 1/3 of patients they can be present. Performing LSG on post-COVID patients did not seem to increase perioperative morbidity.}, } @article {pmid36315942, year = {2022}, author = {Chambers, LC and Beaudoin, FL}, title = {A Longitudinal Study of COVID-19 Sequelae and Immunity.}, journal = {Annals of internal medicine}, volume = {175}, number = {12}, pages = {W153}, doi = {10.7326/L22-0330}, pmid = {36315942}, issn = {1539-3704}, mesh = {Humans ; Longitudinal Studies ; *COVID-19 ; }, } @article {pmid36315558, year = {2022}, author = {Barreto, APA and Barreto Filho, MA and Duarte, LC and Cerqueira-Silva, T and Camelier, A and Tavares, NM and Barral-Netto, M and Boaventura, V and Lima, MCC and , }, title = {Metabolic disorders and post-acute hospitalization in black/mixed-race patients with long COVID in Brazil: A cross-sectional analysis.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276771}, pmid = {36315558}, issn = {1932-6203}, mesh = {Humans ; Female ; Male ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Brazil/epidemiology ; Pandemics ; Quality of Life ; Hospitalization ; *Metabolic Diseases ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Although low-middle income countries have been disproportionately affected by the COVID-19 pandemic, there is scarce information about the impact of long COVID on their population. This study aimed to evaluate long COVID symptomatology, complications (hospital readmission and metabolic disorders), and main clinical features that impact Quality of Life (QoL).

METHODS: This cross-sectional study provides a detailed clinical and laboratory picture of individuals who presented residual symptoms after mild to severe acute COVID-19. Between Aug-2020 to Sep-2021, long COVID patients were evaluated in a reference center for long COVID in Bahia State, Brazil. The EQ-5D-5L questionnaire accessed QoL.

RESULTS: A total of 1164 (52 ±13.4 years, 57% female, 88% black/mixed-race) were evaluated 2.3 [IQR = 1.6-3.7] months after mild (n = 351, 30.2%), moderate (338, 29.0%) or severe (475, 40.8%) acute illness. Dyspnea (790, 67.9%), fatigue (738, 63.5%), and chest pain (525, 42.9%) were the most frequent residual symptoms regardless of acute severity, affecting the QoL of 88.9% of patients (n/N-826/925), mainly the domains of anxiety/depression and pain/discomfort. High levels of HbA1c were detected for 175 out of 664 patients (26.6%), 40% of them without a previous diagnosis of diabetes mellitus. Of note, hospital admission one-to-three months after the acute phase of disease was required for 51 (4.4%) patients.

CONCLUSION: In this majority-black/mixed-race population, long COVID was associated with post-acute hospitalization, newly diagnosed diabetes mellitus, and decreased QoL, particularly in women and regardless of disease severity of acute infection, suggesting important implications for health care system.}, } @article {pmid36315323, year = {2023}, author = {DeMars, J and Brown, DA and Angelidis, I and Jones, F and McGuire, F and O'Brien, KK and Oller, D and Pemberton, S and Tarrant, R and Verduzco-Gutierrez, M and Gross, DP}, title = {What is Safe Long COVID Rehabilitation?.}, journal = {Journal of occupational rehabilitation}, volume = {33}, number = {2}, pages = {227-230}, pmid = {36315323}, issn = {1573-3688}, mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, } @article {pmid36314555, year = {2022}, author = {Adler, L and Gazit, S and Pinto, Y and Perez, G and Mizrahi Reuveni, M and Yehoshua, I and Hoffman, R and Azuri, J and Patalon, T}, title = {Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study.}, journal = {Scandinavian journal of primary health care}, volume = {40}, number = {3}, pages = {342-349}, pmid = {36314555}, issn = {1502-7724}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; Dyspnea/epidemiology ; }, abstract = {OBJECTIVE: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID.

DESIGN: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages.

SETTING: Israeli general practice.

SUBJECTS: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and, 936 without a history of SARS-CoV-2 infection.

MAIN OUTCOME MEASURES: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms.

RESULTS: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness.

CONCLUSION: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.Key PointsLong-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.}, } @article {pmid36314341, year = {2022}, author = {Güven, D and Buluş, AD}, title = {Clinical and laboratory predictors of long-COVID in children: a single center retrospective study.}, journal = {European review for medical and pharmacological sciences}, volume = {26}, number = {20}, pages = {7695-7704}, doi = {10.26355/eurrev_202210_30046}, pmid = {36314341}, issn = {2284-0729}, mesh = {Child ; Humans ; *COVID-19 ; *Pneumonia, Viral ; *Coronavirus Infections ; Pandemics ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The majority of children experience a mild course of acute Coronavirus Disease 2019 (COVID-19). Only few studies have looked at long-term recovery from COVID-19 infection in children. The purpose of this study was to identify the predictors of long-COVID by performing a thorough analysis of the clinical, laboratory, and demographic characteristics of children with COVID-19.

PATIENTS AND METHODS: Between August and October 2021, data were obtained retrospectively from the medical records of 251 children diagnosed with COVID-19 at a tertiary single-center hospital. The prognostic effects of admission-related factors were compared between patients who experienced long-lasting symptoms and those who did not.

RESULTS: Long-COVID symptoms were noted in 12.4% of patients. Joint pain (7.6%), lumbago (4.8%), and headache (3.2%) were the most common symptoms. The mean onset of long-COVID symptoms was 1.35±0.49 months. The onset of long-COVID symptoms was 4 weeks after initial diagnosis in 64.5% of patients and 4-8 weeks later in 35.5% of the patients. The mean duration of long-COVID symptoms was 5.32±2.51 months. Children with long-COVID had higher leukocytes, neutrophils, monocytes, basophils, platelets, and D-dimer when compared with patients without long-COVID (p < 0.001). Leukocytes, neutrophils, monocytes, platelets, and D-dimer had the highest AUC in the ROC analysis (0.694, 0.658, 0.681, 0.667, and 0.612, respectively) and were statistically significant.

CONCLUSIONS: Despite the majority of children with COVID-19 having mild or asymptomatic acute disease, the majority of long-COVID symptoms were associated with functional impairment between 1 and 9 months after the start of the infection. Increased leukocytes, monocytes, neutrophils, platelets, and D-dimer appear to be the most powerful laboratory predictors for long-COVID and monitoring these predictors may assist clinicians to identify and follow-up patients with higher risk for long-COVID.}, } @article {pmid36314211, year = {2023}, author = {Golzari-Sorkheh, M and Weaver, DF and Reed, MA}, title = {COVID-19 as a Risk Factor for Alzheimer's Disease.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {91}, number = {1}, pages = {1-23}, doi = {10.3233/JAD-220800}, pmid = {36314211}, issn = {1875-8908}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Alzheimer Disease/epidemiology/complications ; Neuroinflammatory Diseases ; *Nervous System Diseases/etiology ; Risk Factors ; }, abstract = {Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although a primarily respiratory disease, recent reports indicate that it also affects the central nervous system (CNS). Over 25% of COVID-19 patients report neurological symptoms such as memory loss, anosmia, hyposmia, confusion, and headaches. The neurological outcomes may be a result of viral entry into the CNS and/or resulting neuroinflammation, both of which underlie an elevated risk for Alzheimer's disease (AD). Herein, we ask: Is COVID-19 a risk factor for AD? To answer, we identify the literature and review mechanisms by which COVID-19-mediated neuroinflammation can contribute to the development of AD, evaluate the effects of acute versus chronic phases of infection, and lastly, discuss potential therapeutics to address the rising rates of COVID-19 neurological sequelae.}, } @article {pmid36313487, year = {2022}, author = {Schulze, H and Charles James, J and Trampe, N and Richter, D and Pakeerathan, T and Siems, N and Ayzenberg, I and Gold, R and Faissner, S}, title = {Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {979152}, pmid = {36313487}, issn = {1664-2295}, abstract = {OBJECTIVE: Regarding pathogenesis, clinical manifestations, at-risk individuals, and diagnostic methods for stratifying patients for therapeutic approaches, our understanding of post-COVID syndrome is limited. Here, we set out to assess sociodemographic and clinical aspects in patients with the long-COVID and post-COVID syndrome.

METHODS: We performed a cross-sectional analysis of patients presenting at our specialized university hospital outpatient clinic. We assessed patients' clinical presentation, fatigue, symptoms of depression and anxiety, and impairment of smell.

RESULTS: A total of 101 patients were included (73.3% female), of whom 78.2% had a mild course of COVID-19. At presentation, 93.1% suffered from fatigue, 82.2% from impaired concentration, and 79.2% from impaired memory, 53.5% had impaired sleep. The most common secondary diagnosis found in our cohort was thyroid disease. Fatigue analysis showed that 81.3% of female and 58.8% of male patients had severe combined fatigue. Female gender was an independent risk factor for severe fatigue (severe cognitive fatigue OR = 8.045, p = 0.010; severe motor fatigue OR = 7.698, p = 0.013). Males suffered from more depressive symptoms, which correlated positively with the duration of symptom onset. 70.3% of patients with anamnestic smell impairment had hyposmia, and 18.9% were anosmic.

INTERPRETATION: Most long-COVID patients suffered from severe fatigue, with the female sex as an independent risk factor. Fatigue was not associated with symptoms of depression or anxiety. Patients with long-COVID symptoms should receive an interdisciplinary diagnostic and therapeutic approach depending on the clinical presentation.}, } @article {pmid36313404, year = {2022}, author = {Mortazavi, SA and Bevelacqua, JJ and Welsh, JS and Masoumi, SJ and Bahaaddini Beigy Zarandi, BF and Ghadimi-Moghadam, A and Haghani, M and Mortazavi, SMJ}, title = {The Paradox of COVID-19 in Sub-Saharan Africa: Why it is More Unethical Not to Investigate Low Dose Radiotherapy for COVID-19.}, journal = {Journal of biomedical physics & engineering}, volume = {12}, number = {5}, pages = {539-542}, pmid = {36313404}, issn = {2251-7200}, abstract = {An accumulating body of evidence shows that various ethnicities are differentially affected by SARS-COV-2 infection. Moreover, some evidence shows that due to the vaccine inequity and millions of people living with HIV, a major catastrophe could occur in African countries that possibly affects the whole world. Given the possibility that Neanderthal genes confer a slight increase in susceptibility, this difference, at least to some extent, might possibly decrease the risk of the emergence of new SARS-CoV-2 variants among black people in Africa. Recent studies show less death and fewer cases among the ethnic group classified as "Black Africans". Although Neanderthal DNA might explain some differences in morbidity and mortality of COVID-19, a multitude of confounders complicate things to where drawing definite conclusions is hard or even impossible. Using selective-pressure-free treatments (e.g. low dose radiotherapy) for COVID-19 pneumonia would be of crucial importance everywhere, but particularly in sub-Saharan Africa, where "long COVID" in millions of people with HIV paves the road for the more frequent emergence of new variants.}, } @article {pmid36311179, year = {2022}, author = {Mitsuyama, Y and Yamakawa, K and Kayano, K and Maruyama, M and Umemura, Y and Wada, T and Fujimi, S}, title = {Residual persistence of cytotoxicity lymphocytes and regulatory T cells in patients with severe coronavirus disease 2019 over a 1-year recovery process.}, journal = {Acute medicine & surgery}, volume = {9}, number = {1}, pages = {e803}, pmid = {36311179}, issn = {2052-8817}, abstract = {AIM: To clarify the immune cellular changes in critically ill patients recovering from coronavirus disease 2019 (COVID-19).

METHODS: The immune response of peripheral blood mononuclear cells from patients with severe COVID-19 in different stages of recovery (3, 6, and 12 months from hospitalization) was evaluated by single-cell mass cytometry. Immunological changes in patients were compared with those in age-matched healthy donors.

RESULTS: Three patients with severe COVID-19 were compared with four healthy donors. In the patients, there was an increase in the cell density of CD4- and CD8-positive T lymphocytes, and B cells, over the course of the recovery period. CD4- and CD8-positive T lymphocytes expressing T-bet and granzyme B (Gzm B) in patients were abundant during all recovery periods. The level of regulatory T cells remained high throughout the year. The levels of natural killer (NK) cells in patients were higher than in those in the healthy donors, and the frequency of CD16[+] NK cells expressing Gzm B increased throughout the year.

CONCLUSION: Patients recovering from severe COVID-19 showed persistence of cytotoxic lymphocytes, NK cells, and regulatory T cells throughout the posthospitalization year of recovery.}, } @article {pmid36310021, year = {2022}, author = {Nagel, C and Olschewski, H and Sorichter, S and Uezgoer, G and Diehm, C and Huppert, P and Iber, T and Herth, F and Harutyunova, S and Marra, AM and Benjamin, N and Salkić, A and Grünig, E and Egenlauf, B}, title = {Impairment of Inspiratory Muscle Function after COVID-19.}, journal = {Respiration; international review of thoracic diseases}, volume = {101}, number = {11}, pages = {981-989}, doi = {10.1159/000527361}, pmid = {36310021}, issn = {1423-0356}, mesh = {Humans ; Adult ; Middle Aged ; *COVID-19/complications ; Respiratory Muscles ; Vital Capacity/physiology ; Dyspnea/etiology ; Muscle Strength/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting.

METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021.

RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters.

CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.}, } @article {pmid36304797, year = {2022}, author = {Delalić, Đ and Jug, J and Prkačin, I}, title = {ARTERIAL HYPERTENSION FOLLOWING COVID-19: A RETROSPECTIVE STUDY OF PATIENTS IN A CENTRAL EUROPEAN TERTIARY CARE CENTER.}, journal = {Acta clinica Croatica}, volume = {61}, number = {Suppl 1}, pages = {23-27}, pmid = {36304797}, issn = {1333-9451}, mesh = {Humans ; Retrospective Studies ; *Coronavirus ; *COVID-19/complications/epidemiology ; Tertiary Care Centers ; *Hypertension/epidemiology ; Blood Pressure/physiology ; }, abstract = {The aim of this study was to determine the frequency of newly verified or worsened existing hypertension in patients who had coronavirus 2019 (COVID-19). To be categorized as a COVID-19 patient, a positive reverse-transcription polymerase chain reaction test at a single point in time was required. The patients' age, history, laboratory values and antihypertensive therapy of patients were recorded. In one year, 32 of 199 patients studied had either newly verified (15) or worsened existing (17) arterial hypertension. Among those patients, the median time from a verified infection to the onset of symptoms was 3 months. When the patients were divided into groups, 4 were in the acute, 11 in the sub-acute, 8 in the chronic and 9 in the "long COVID" group. Compared to the rest of the study population, patients presenting with arterial hypertension had significantly higher systolic (median 141 mmHg vs 130 mmHg, p<0.001) and diastolic (median 93 mmHg vs 80 mmHg, p<0.001) blood pressure and were significantly younger (median 51 vs 59 years, p 0.032). Arterial hypertension following COVID-19, either newly verified or worsened existing, is a relatively common occurrence (16% of our patient pool), indicating that more effort should be directed at evaluating the blood pressure values of patients following COVID-19.}, } @article {pmid36304574, year = {2022}, author = {Li, F and Zhang, X and Comellas, AP and Hoffman, EA and Yang, T and Lin, CL}, title = {Contrastive learning and subtyping of post-COVID-19 lung computed tomography images.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {999263}, pmid = {36304574}, issn = {1664-042X}, support = {T32 HL144461/HL/NHLBI NIH HHS/United States ; }, abstract = {Patients who recovered from the novel coronavirus disease 2019 (COVID-19) may experience a range of long-term symptoms. Since the lung is the most common site of the infection, pulmonary sequelae may present persistently in COVID-19 survivors. To better understand the symptoms associated with impaired lung function in patients with post-COVID-19, we aimed to build a deep learning model which conducts two tasks: to differentiate post-COVID-19 from healthy subjects and to identify post-COVID-19 subtypes, based on the latent representations of lung computed tomography (CT) scans. CT scans of 140 post-COVID-19 subjects and 105 healthy controls were analyzed. A novel contrastive learning model was developed by introducing a lung volume transform to learn latent features of disease phenotypes from CT scans at inspiration and expiration of the same subjects. The model achieved 90% accuracy for the differentiation of the post-COVID-19 subjects from the healthy controls. Two clusters (C1 and C2) with distinct characteristics were identified among the post-COVID-19 subjects. C1 exhibited increased air-trapping caused by small airways disease (4.10%, p = 0.008) and diffusing capacity for carbon monoxide %predicted (DLCO %predicted, 101.95%, p < 0.001), while C2 had decreased lung volume (4.40L, p < 0.001) and increased ground glass opacity (GGO%, 15.85%, p < 0.001). The contrastive learning model is able to capture the latent features of two post-COVID-19 subtypes characterized by air-trapping due to small airways disease and airway-associated interstitial fibrotic-like patterns, respectively. The discovery of post-COVID-19 subtypes suggests the need for different managements and treatments of long-term sequelae of patients with post-COVID-19.}, } @article {pmid36304538, year = {2022}, author = {Jaeger, BR and Arron, HE and Kalka-Moll, WM and Seidel, D}, title = {The potential of heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.)-apheresis for patients with severe acute or chronic COVID-19.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {1007636}, pmid = {36304538}, issn = {2297-055X}, abstract = {Patients with long COVID and acute COVID should benefit from treatment with H.E.L.P. apheresis, which is in clinical use for 37 years. COVID-19 can cause a severe acute multi-organ illness and, subsequently, in many patients the chronic illness long-COVID/PASC. The alveolar tissue and adjacent capillaries show inflammatory and procoagulatory activation with cell necrosis, thrombi, and massive fibrinoid deposits, namely, unsolvable microthrombi, which results in an obstructed gas exchange. Heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.) apheresis solves these problems by helping the entire macro- and microcirculation extracorporeally. It uses unfractionated heparin, which binds the spike protein and thereby should remove the virus (debris). It dissolves the forming microthrombi without bleeding risk. It removes large amounts of fibrinogen (coagulation protein), which immediately improves the oxygen supply in the capillaries. In addition, it removes the precursors of both the procoagulatory and the fibrinolytic cascade, thus de-escalating the entire hemostaseological system. It increases myocardial, cerebral, and pulmonary blood flow rates, and coronary flow reserve, facilitating oxygen exchange in the capillaries, without bleeding risks. Another factor in COVID is the "cytokine storm" harming microcirculation in the lungs and other organs. Intervention by H.E.L.P. apheresis could prevent uncontrollable coagulation and inflammatory activity by removing cytokines such as interleukin (IL)-6, IL-8, and TNF-α, and reduces C-reactive protein, and eliminating endo- and ecto-toxins, without touching protective IgM/IgG antibodies, leukocyte, or platelet function. The therapy can be used safely in combination with antiviral drugs, antibiotics, anticoagulants, or antihypertensive drugs. Long-term clinical experience with H.E.L.P. apheresis shows it cannot inflict harm upon patients with COVID-19.}, } @article {pmid36302947, year = {2022}, author = {Thiele, K and Balfanz, P and Müller, T and Hartmann, B and Spiesshoefer, J and Grebe, J and Müller-Wieland, D and Marx, N and Dreher, M and Daher, A}, title = {Cardiopulmonary work up of patients with and without fatigue 6 months after COVID-19.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18038}, pmid = {36302947}, issn = {2045-2322}, mesh = {Humans ; *COVID-19 ; Quality of Life ; Ventricular Function, Left ; Stroke Volume ; *Ventricular Dysfunction, Left ; Fatigue/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {The pathogenesis of long-Covid symptoms remains incompletely understood. Therefore, we aimed to determine cardiopulmonary limitations 6 months after surviving COVID-19 using pulmonary function tests, echocardiographic studies to the point of analysis of global-longitudinal-strain (GLS), which describes the cycling myocardium deformation and provides better data on left ventricular (LV) dysfunction than LV ejection fraction (LVEF), and validated questionnaires. Overall, 60 consecutive hospitalized patients were included (61 ± 2 years, 40% treated in the ICU). At follow-up (194 ± 3 days after discharge), fatigue was the most prevalent symptom (28%). Patients with fatigue were more symptomatic overall and characterized by worse quality of life (QoL) scores compared to patients without fatigue (all p < 0.05), mainly due to limited mobility and high symptom burden. While PFT variables and LVEF were normal in the vast majority of patients (LVEF = 52% (45-52%)), GLS was significantly reduced (- 15% (- 18 to - 14%)). However, GLS values were not different between patients with and without fatigue. In conclusion, fatigue was the most prevalent long-Covid symptom in our cohort, which was associated with worse QoL mainly due to limited mobility and the high burden of concomitant symptoms. Patients showed a subtle myocardial dysfunction 6 months after surviving COVID-19, but this did not relate to the presence of fatigue.}, } @article {pmid36301542, year = {2022}, author = {Perlis, RH and Santillana, M and Ognyanova, K and Safarpour, A and Lunz Trujillo, K and Simonson, MD and Green, J and Quintana, A and Druckman, J and Baum, MA and Lazer, D}, title = {Prevalence and Correlates of Long COVID Symptoms Among US Adults.}, journal = {JAMA network open}, volume = {5}, number = {10}, pages = {e2238804}, pmid = {36301542}, issn = {2574-3805}, support = {R01 GM130668/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Acute Disease ; Betacoronavirus ; *Coronavirus Infections/epidemiology ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Pandemics/prevention & control ; *Pneumonia, Viral/epidemiology ; Prevalence ; SARS-CoV-2 ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Persistence of COVID-19 symptoms beyond 2 months, or long COVID, is increasingly recognized as a common sequela of acute infection.

OBJECTIVES: To estimate the prevalence of and sociodemographic factors associated with long COVID and to identify whether the predominant variant at the time of infection and prior vaccination status are associated with differential risk.

This cross-sectional study comprised 8 waves of a nonprobability internet survey conducted between February 5, 2021, and July 6, 2022, among individuals aged 18 years or older, inclusive of all 50 states and the District of Columbia.

MAIN OUTCOMES AND MEASURES: Long COVID, defined as reporting continued COVID-19 symptoms beyond 2 months after the initial month of symptoms, among individuals with self-reported positive results of a polymerase chain reaction test or antigen test.

RESULTS: The 16 091 survey respondents reporting test-confirmed COVID-19 illness at least 2 months prior had a mean age of 40.5 (15.2) years; 10 075 (62.6%) were women, and 6016 (37.4%) were men; 817 (5.1%) were Asian, 1826 (11.3%) were Black, 1546 (9.6%) were Hispanic, and 11 425 (71.0%) were White. From this cohort, 2359 individuals (14.7%) reported continued COVID-19 symptoms more than 2 months after acute illness. Reweighted to reflect national sociodemographic distributions, these individuals represented 13.9% of those who had tested positive for COVID-19, or 1.7% of US adults. In logistic regression models, older age per decade above 40 years (adjusted odds ratio [OR], 1.15; 95% CI, 1.12-1.19) and female gender (adjusted OR, 1.91; 95% CI, 1.73-2.13) were associated with greater risk of persistence of long COVID; individuals with a graduate education vs high school or less (adjusted OR, 0.67; 95% CI, 0.56-0.79) and urban vs rural residence (adjusted OR, 0.74; 95% CI, 0.64-0.86) were less likely to report persistence of long COVID. Compared with ancestral COVID-19, infection during periods when the Epsilon variant (OR, 0.81; 95% CI, 0.69-0.95) or the Omicron variant (OR, 0.77; 95% CI, 0.64-0.92) predominated in the US was associated with diminished likelihood of long COVID. Completion of the primary vaccine series prior to acute illness was associated with diminished risk for long COVID (OR, 0.72; 95% CI, 0.60-0.86).

CONCLUSIONS AND RELEVANCE: This study suggests that long COVID is prevalent and associated with female gender and older age, while risk may be diminished by completion of primary vaccination series prior to infection.}, } @article {pmid36301107, year = {2022}, author = {Vilas Boas de Melo, C and Peters, F and van Dijken, H and Lenz, S and van de Ven, K and Wijsman, L and Gomersbach, A and Schouten, T and van Kasteren, PB and van den Brand, J and de Jonge, J}, title = {Influenza Infection in Ferrets with SARS-CoV-2 Infection History.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0138622}, pmid = {36301107}, issn = {2165-0497}, mesh = {Animals ; Humans ; *Influenza, Human ; SARS-CoV-2 ; Ferrets ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; *Influenza A Virus, H1N1 Subtype ; Pandemics ; }, abstract = {Nonpharmaceutical interventions (NPIs) to contain the SARS-CoV-2 pandemic drastically reduced human-to-human interactions, decreasing the circulation of other respiratory viruses, as well. Consequently, influenza virus circulation, which is normally responsible for 3 to 5 million hospitalizations per year globally, was significantly reduced. With the downscaling of the NPI countermeasures, there is a concern for increased influenza disease, particularly in individuals suffering from postacute effects of SARS-CoV-2 infection. To investigate this, we performed a sequential influenza H1N1 infection 4 weeks after an initial SARS-CoV-2 infection in ferrets. Upon H1N1 infection, ferrets that were previously infected with SARS-CoV-2 showed an increased tendency to develop clinical signs, compared to the control H1N1-infected animals. A histopathological analysis indicated only a slight increase for type II pneumocyte hyperplasia and bronchitis. Thus, the effects of the sequential infection appeared minor. However, ferrets were infected with B.1.351-SARS-CoV-2, the beta variant of concern, which replicated poorly in our model. The histopathology of the respiratory organs was mostly resolved 4 weeks after the SARS-CoV-2 infection, with only reminiscent histopathological features in the upper respiratory tract. Nevertheless, SARS-CoV-2 specific cellular and humoral responses were observed, confirming an established infection. On account of a modest trend toward the enhancement of the influenza disease, even upon a mild SARS-CoV-2 infection, our findings suggest that a stronger SARS-CoV-2 infection and its consequent, long-term effects could have a greater impact on the outcome of disease after a sequential influenza infection. Hence, the influenza vaccination of individuals suffering from postacute SARS-CoV-2 infection effects may be considered an avertible measure for such a scenario. IMPORTANCE During the COVID-19 pandemic, the use of face masks, social distancing, and isolation were effective not only in decreasing the circulation of SARS-CoV-2 but also in reducing other respiratory viruses, such as influenza. With fewer restrictions currently in place, influenza is slowly returning. In the meantime, people who are still suffering from long-COVID could be more vulnerable to an influenza virus infection and could develop a more severe influenza disease. This study provides directions to the effect of a previous SARS-CoV-2 exposure on influenza disease severity in a ferret model. This model is highly valuable to test sequential infections under controlled settings for translation to humans. We could not induce clear long-term COVID-19 effects, as the SARS-CoV-2 infections in the ferrets were mild. However, we still observed a slight increase in influenza disease severity compared to ferrets that had not encountered SARS-CoV-2 before. Therefore, it may be advisable to include long-COVID patients as a risk group for influenza vaccination.}, } @article {pmid36298551, year = {2022}, author = {Buchhorn, R}, title = {Dysautonomia in Children with Post-Acute Sequelae of Coronavirus 2019 Disease and/or Vaccination.}, journal = {Vaccines}, volume = {10}, number = {10}, pages = {}, pmid = {36298551}, issn = {2076-393X}, abstract = {UNLABELLED: Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood.

METHODS: In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published.

RESULTS: All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2.

CONCLUSION: The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.}, } @article {pmid36298472, year = {2022}, author = {Rapti, V and Tsaganos, T and Vathiotis, IA and Syrigos, NK and Li, P and Poulakou, G}, title = {New Insights into SARS-CoV-2 and Cancer Cross-Talk: Does a Novel Oncogenesis Driver Emerge?.}, journal = {Vaccines}, volume = {10}, number = {10}, pages = {}, pmid = {36298472}, issn = {2076-393X}, abstract = {Since the pandemic's onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. So far, several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms. Excessive cytokine release, impaired T-cell responses, aberrant activation of regulatory signaling pathways (e.g., JAK-STAT, MAPK, NF-kB), and tissue damage, hallmarks of COVID-19 disease course, are also present in the tumor microenvironment. Therefore, the intersection of COVID-19 and cancer is partially recognized and the long-term effects of the virus on oncogenesis and cancer progression have not been explored yet. Herein, we present an up-to-date review of the current literature regarding COVID-19 and cancer cross-talk, as well as the oncogenic pathways stimulated by SARS-CoV-2.}, } @article {pmid36296272, year = {2022}, author = {Forsyth, CB and Zhang, L and Bhushan, A and Swanson, B and Zhang, L and Mamede, JI and Voigt, RM and Shaikh, M and Engen, PA and Keshavarzian, A}, title = {The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells.}, journal = {Microorganisms}, volume = {10}, number = {10}, pages = {}, pmid = {36296272}, issn = {2076-2607}, support = {NSF 2031754//National Science Foundation/ ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the "Cytokine Storm", which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or "Long COVID". Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1-S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.}, } @article {pmid36295814, year = {2022}, author = {Alenazy, MF and Aljohar, HI and Alruwaili, AR and Daghestani, MH and Alonazi, MA and Labban, RS and El-Ansary, AK and Balto, HA}, title = {Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications.}, journal = {Metabolites}, volume = {12}, number = {10}, pages = {}, pmid = {36295814}, issn = {2218-1989}, support = {RSP2022R179//King Saud University, Riyadh, Saudi Arabia/ ; }, abstract = {Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.}, } @article {pmid36295660, year = {2022}, author = {Mutiawati, E and Kusuma, HI and Fahriani, M and Harapan, H and Syahrul, S and Musadir, N}, title = {Headache in Post-COVID-19 Patients: Its Characteristics and Relationship with the Quality of Life.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {10}, pages = {}, pmid = {36295660}, issn = {1648-9144}, mesh = {Humans ; *Quality of Life ; *COVID-19/complications ; Cross-Sectional Studies ; Headache/etiology ; Logistic Models ; }, abstract = {Little is known on the characteristics of headaches associated with coronavirus disease 2019 (COVID-19) in Indonesia. The objective of this study was to describe the characteristics of headache in post-COVID-19 patients, and its impact on the patients' quality of life (QoL), as well as to determine the associated determinants of the poor QoL. A cross-sectional study was conducted in Banda Aceh, Indonesia. The demographic characteristics, clinical symptoms of COVID-19, characteristics of headache, and the QoL were collected and assessed. Headache was diagnosed and characterized using the International Classification of Headache Disorders, version 3 (ICHD-3). QoL was assessed using a Short Form 36 Health Survey (SF-36) tool. A logistic regression model was used to investigate the associated determinants of poor QoL in post-COVID-19 patients. A total of 215 post-COVID-19 patients were included in the final analysis, and 21.4% (46/215) of them had a poor QoL due to headache following COVID-19. Those who were unemployed and who contracted COVID-19 less than three months prior to the study had higher odds of having poor QoL compared to those who were employed and who contracted COVID-19 more than three months prior to the study. Low QoL was also related to headache that occurred less than one month after recovering from COVID-19 (compared to that which occurred longer than one month after); had a high frequency; had a combination sensation of pulsating, pressing, fiery, and stabbing pain; had a high severity score; and had additional symptoms accompanying the headache. In conclusion, headache related to COVID-19 is associated with low QoL among post-COVID-19 patients. A guideline on prevention measures of headache on COVID-19 patients, therefore, needs to be established to avoid long-term consequences.}, } @article {pmid36295554, year = {2022}, author = {Nakano, Y and Otsuka, Y and Honda, H and Sunada, N and Tokumasu, K and Sakurada, Y and Matsuda, Y and Hasegawa, T and Ochi, K and Hagiya, H and Kataoka, H and Ueda, K and Otsuka, F}, title = {Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {10}, pages = {}, pmid = {36295554}, issn = {1648-9144}, mesh = {Humans ; *COVID-19/complications ; Japan/epidemiology ; SARS-CoV-2 ; Fatigue/epidemiology/etiology ; }, abstract = {Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.}, } @article {pmid36294991, year = {2022}, author = {Schambeck, SE and Mateyka, LM and Burrell, T and Graf, N and Brill, I and Stark, T and Protzer, U and Busch, DH and Gerhard, M and Riehl, H and Poppert, H}, title = {Two-Year Follow-Up on Chemosensory Dysfunction and Adaptive Immune Response after Infection with SARS-CoV-2 in a Cohort of 44 Healthcare Workers.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {36294991}, issn = {2075-1729}, abstract = {Persistent chemosensory dysfunction (PCD) is a common symptom of long-COVID. Chemosensory dysfunction (CD) as well as SARS-CoV-2-specific antibody levels and CD8[+] T-cell immunity were investigated in a cohort of 44 healthcare workers up to a median of 721 days after a positive PCR test. CD was assessed using questionnaires and psychophysical screening tests. After 721 days, 11 of 44 (25%) participants reported PCD, with five describing an impaired quality of life. One participant reported hyperosmia (increased sense of smell). The risk of PCD at 721 days was higher for participants reporting qualitative changes (parosmia (altered smell), dysgeusia (altered taste), or phantosmia (hallucination of smell)) during initial infection than in those with isolated quantitative losses during the first COVID-19 infection (62.5% vs. 7.1%). The main recovery rate occurred within the first 100 days and did not continue until follow-up at 2 years. No correlation was found between antibody levels and CD, but we observed a trend of a higher percentage of T-cell responders in participants with CD. In conclusion, a significant proportion of patients suffer from PCD and impaired quality of life 2 years after initial infection. Qualitative changes in smell or taste during COVID-19 pose a higher risk for PCD.}, } @article {pmid36294534, year = {2022}, author = {Harenwall, S and Heywood-Everett, S and Henderson, R and Smith, J and McEnery, R and Bland, AR}, title = {The Interactive Effects of Post-Traumatic Stress Symptoms and Breathlessness on Fatigue Severity in Post-COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {11}, number = {20}, pages = {}, pmid = {36294534}, issn = {2077-0383}, abstract = {BACKGROUND: Post-traumatic stress symptoms (PTSS) and breathlessness have been well documented in the acute phase of COVID-19 as well as in Post-COVID-19 Syndrome (PCS), commonly known as Long-COVID. The present study aimed to explore whether PTSS and breathlessness interact to exacerbate fatigue among individuals recovering from PCS, similar to the effects evidenced in other health conditions that feature respiratory distress..

METHODS: Outcome measures were collected from 154 participants reporting persistent fatigue following acute COVID-19 infection who were enrolled in a 7-week rehabilitation course provided by the Primary Care Wellbeing Service (PCWBS) in Bradford District Care NHS Foundation Trust (BDCFT).

RESULTS: Hierarchical multiple linear regression revealed that fatigue severity was associated with a significant interaction between PTSS and breathlessness, even when controlling for pre-COVID health related quality of life (HRQoL), age, symptom duration and hospital admittance during the acute phase. Furthermore, improvements in fatigue following rehabilitation were significantly associated with improvements in PTSS.

CONCLUSIONS: PTSS may be an important therapeutic target in multidisciplinary rehabilitation for reducing fatigue in the recovery from PCS. It is therefore important that treatment for PCS takes a biopsychosocial approach to recovery, putting emphasis on direct and indirect psychological factors which may facilitate or disrupt physical recovery. This highlights the need for all PCS clinics to screen for PTSD and if present, target as a priority in treatment to maximise the potential for successful rehabilitation.}, } @article {pmid36294444, year = {2022}, author = {Shechter, A and Yelin, D and Margalit, I and Abitbol, M and Morelli, O and Hamdan, A and Vaturi, M and Eisen, A and Sagie, A and Kornowski, R and Shapira, Y}, title = {Assessment of Adult Patients with Long COVID Manifestations Suspected as Cardiovascular: A Single-Center Experience.}, journal = {Journal of clinical medicine}, volume = {11}, number = {20}, pages = {}, pmid = {36294444}, issn = {2077-0383}, abstract = {Background: Persistent symptoms affect a subset of coronavirus disease 2019 (COVID-19) survivors. Some of these may be cardiovascular (CV)-related. Objective: To assess the burden of objective CV morbidity among, and to explore the short-term course experienced by, COVID-19 patients with post-infectious symptomatology suspected as CV. Methods: This was a single-center, retrospective analysis of consecutive adult patients with new-onset symptoms believed to be CV following recovery from COVID-19, who had been assessed at a dedicated 'Cardio'-COVID clinic between June 2020 and June 2021. All participants were followed for 1 year for symptomatic course and the occurrence of new CV diagnoses and major adverse cardiovascular events (MACE). Results: A total of 96 patients (median age 54 (IQR, 44-64) years, 52 (54%) females) were included in the final analysis. Initial visits occurred within a median of 142 days after the diagnosis of acute COVID. Nearly all (99%) patients experienced a symptomatic acute illness, which was graded as severe in 26 (27%) cases according to the National Institutes of Health (NIH) criteria. Long-COVID symptoms included mainly dyspnea and fatigue. While the initial work-up was mostly normal, 45% of the 11 cardiac magnetic resonance studies performed revealed pathologies. New CV diagnoses were made in nine (9%) patients and mainly included myocarditis that later resolved. An abnormal spirometry was the only variable associated with these. No MACE were recorded. Fifty-two (54%) participants felt that their symptoms improved. No association was found between CV morbidity and symptomatic course. Conclusions: In our experience, long-COVID symptoms of presumed CV origin signified actual CV disease in a minority of patients who, irrespective of the final diagnosis, faced a fair 1-year prognosis.}, } @article {pmid36294186, year = {2022}, author = {Hiremath, S and Doukrou, M and Flannery, H and Carey, C and Gregorowski, A and Ward, J and Hargreaves, D and Segal, TY}, title = {Key Features of a Multi-Disciplinary Hospital-Based Rehabilitation Program for Children and Adolescents with Moderate to Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36294186}, issn = {1660-4601}, mesh = {Child ; Humans ; Adolescent ; *Fatigue Syndrome, Chronic/therapy ; Retrospective Studies ; *COVID-19 ; Hospitals ; }, abstract = {PURPOSE OF THE STUDY: There is limited published data on treatment or outcomes of children and young people (CYP) with moderate or severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Here, we describe outcomes of moderate and severe ME/CFS in CYP treated in a tertiary adolescent service. This information is useful when planning services for CYP and families affected by moderate/severe ME/CFS and to guide future management trials and commissioning decisions.

STUDY DESIGN: A retrospective review was conducted of medical records of the 27 CYP who received ward-based treatment in 2015. Notes were retrospectively reviewed to assess progress in four markers of wellbeing over the period of treatment: (i) mobility, (ii) education, (iii) sleep and (iv) involvement in social/recreational activities.

RESULTS: A total of 23/27 (85%) showed improvement in one or more domains over their period of ward-based therapy. 19/27 (70%) of patients showed improvement in physical ability. In 15/23 patients (65%), there was an improvement in ability to access education, in 12/24 (50%) sleep improved, and 16/27 (59%) demonstrated an improvement in socialising/ability perform recreational activities.

CONCLUSION/IMPLICATIONS: A multidisciplinary hospital-based rehabilitation programme for moderate and severe ME/CFS was associated with improvement in at least one area of wellbeing in 85% of the CYP we reviewed. These data may be used as a baseline to evaluate the impact of other models of delivering care for this patient group. It may be useful when considering other groups such as those affected by Post-COVID Syndrome.}, } @article {pmid36293968, year = {2022}, author = {Messiah, SE and Xie, L and Mathew, MS and Shaikh, S and Veeraswamy, A and Rabi, A and Francis, J and Lozano, A and Ronquillo, C and Sanchez, V and He, W and Weerakoon, SM and Srikanth, N and Borel, M and Kapera, O and Kahn, J}, title = {Comparison of Long-Term Complications of COVID-19 Illness among a Diverse Sample of Children by MIS-C Status.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36293968}, issn = {1660-4601}, mesh = {Male ; Female ; Humans ; Child ; *COVID-19/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; }, abstract = {Most pediatric COVID-19 cases are asymptomatic; however, a small number of children are diagnosed with multisystem inflammatory syndrome in children (MIS-C), a rare but severe condition that is associated with SARS-CoV-2 infection. Persistent symptoms of COVID-19 illness in children diagnosed with/without MIS-C is largely unknown. A retrospective EHR review of patients with COVID-19 illness from one pediatric healthcare system to assess the presence of acute (<30 days) and chronic (≥30, 60-120, and >120 days) long-term COVID symptoms was conducted. Patients/caregivers completed a follow-up survey from March 2021 to January 2022 to assess the presence of long COVID. Results showed that non-MIS-C children (n = 286; 54.49% Hispanic; 19.23% non-Hispanic Black; 5.77% other ethnicity; 79.49% government insurance) were younger (mean age 6.43 years [SD 5.95]) versus MIS-C (n = 26) children (mean age 9.08 years, [SD 4.86]) (p = 0.032). A share of 11.5% of children with MIS-C and 37.8% without MIS-C reported acute long COVID while 26.9% and 15.3% reported chronic long COVID, respectively. Females were almost twice as likely to report long symptoms versus males and those with private insurance were 66% less likely to report long symptoms versus those with government insurance. In conclusion, a substantial proportion of ethnically diverse children from low resource backgrounds with severe COVID illness are reporting long-term impacts. Findings can inform pediatric professionals about this vulnerable population in post-COVID-19 recovery efforts.}, } @article {pmid36293857, year = {2022}, author = {Wrona, M and Skrypnik, D}, title = {New-Onset Diabetes Mellitus, Hypertension, Dyslipidaemia as Sequelae of COVID-19 Infection-Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36293857}, issn = {1660-4601}, support = {502-14-21191730-11315 ; ID: 4089//Poznan University of Medical Sciences/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Diabetes Mellitus/epidemiology/etiology ; *Hypertension/epidemiology/etiology ; *Dyslipidemias/epidemiology/etiology ; Glucose ; Lipids ; }, abstract = {As the population recovers from the coronavirus disease 2019 (COVID-19) pandemic, a subset of individuals is emerging as post-coronavirus disease (post-COVID) patients who experience multifactorial long-term symptoms several weeks after the initial recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this systematic review is to present the latest scientific reports that evaluate changes in glucose levels, blood pressure readings and lipid profiles after recovery from COVID-19 to verify the hypothesis that new-onset diabetes mellitus, arterial hypertension and dyslipidaemia are a possible sequela of a COVID-19 infection. The open access databases PubMed and Google Scholar were searched. Articles investigating patients with residual clinical signs and biochemical alteration indicating diabetes, hypertension and dyslipidaemia at least a month after recovering from COVID-19 were included. It has been shown that a select number of patients were diagnosed with new-onset diabetes, arterial hypertension and dyslipidaemia after COVID-19 infection. Alterations in glucose levels, blood pressure and lipid profiles months after initial infection shows the importance of considering diabetes mellitus, arterial hypertension and dyslipidaemia as part of the multifactorial diagnostic criteria post-COVID to better provide evidence-based clinical care.}, } @article {pmid36293582, year = {2022}, author = {Schaap, G and Wensink, M and Doggen, CJM and van der Palen, J and Vonkeman, HE and Bode, C}, title = {"It Really Is an Elusive Illness"-Post-COVID-19 Illness Perceptions and Recovery Strategies: A Thematic Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {20}, pages = {}, pmid = {36293582}, issn = {1660-4601}, mesh = {Humans ; *COVID-19/epidemiology ; Fatigue ; Qualitative Research ; }, abstract = {A substantial number of patients report persisting symptoms after a COVID-19 infection: so-called post-COVID-19 syndrome. There is limited research on patients' perspectives on post-COVID-19 symptoms and ways to recover. This qualitative study explored the illness perceptions and recovery strategies of patients who had been hospitalised for COVID-19. Differences between recovered and non-recovered patients were investigated. Semi-structured in-depth interviews were held with 24 participating patients (8 recovered and 16 non-recovered) 7 to 12 months after hospital discharge. Data were interpreted using reflexive thematic analysis. Four overarching themes were identified: (I) symptoms after hospital discharge; (II) impact of COVID-19 on daily life and self-identity; (III) uncertainty about COVID-19; and (IV) dealing with COVID-19. Formerly hospitalised post-COVID-19 patients seem to have difficulties with making sense of their illness and gaining control over their recovery. The majority of non-recovered participants continue to suffer mostly from weakness or fatigue, dyspnoea and cognitive dysfunction. No notable differences in illness beliefs were observed between recovered and non-recovered participants.}, } @article {pmid36293160, year = {2022}, author = {Scurati, R and Papini, N and Giussani, P and Alberti, G and Tringali, C}, title = {The Challenge of Long COVID-19 Management: From Disease Molecular Hallmarks to the Proposal of Exercise as Therapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293160}, issn = {1422-0067}, mesh = {Humans ; *COVID-19/therapy ; SARS-CoV-2 ; Quality of Life ; Nerve Growth Factors ; }, abstract = {Long coronavirus disease 19 (COVID-19) is the designation given to a novel syndrome that develops within a few months after infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and that is presenting with increasing incidence because of the numerous cases of infection. Long COVID-19 is characterized by a sequela of clinical symptoms that concern different organs and tissues, from nervous, respiratory, gastrointestinal, and renal systems to skeletal muscle and cardiovascular apparatus. The main common molecular cause for all long COVID-19 facets appears to be related to immune dysregulations, the persistence of inflammatory status, epigenetic modifications, and alterations of neurotrophin release. The prevention and management of long COVID-19 are still inappropriate because many aspects need further clarification. Exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19 depending on training intensity, duration, and continuity. Evidence suggests that it could improve the quality of life of long COVID-19 patients. This review explores the main clinical features and the known molecular mechanisms underlying long COVID-19 in the perspective of considering exercise as a co-medication in long COVID-19 management.}, } @article {pmid36293090, year = {2022}, author = {Odainic, A and Spitzer, J and Szlapa, JB and Schade, S and Krämer, TJ and Neuberger, J and Bode, C and Steinhagen, F and Schmithausen, RM and Wilbring, G and Sib, E and Mutters, NT and Rabenschlag, F and Kettel, L and Woznitza, M and van Bremen, K and Peers, T and Medinger, G and Kudaliyanage, A and Kreutzenbeck, M and Strube, U and Johnson, JM and Mattoon, D and Ball, AJ and Scory, S and McGuire, R and Putensen, C and Abdullah, Z and Latz, C and Schmidt, SV}, title = {Comparative Analysis of Antibody Titers against the Spike Protein of SARS-CoV-2 Variants in Infected Patient Cohorts and Diverse Vaccination Regimes.}, journal = {International journal of molecular sciences}, volume = {23}, number = {20}, pages = {}, pmid = {36293090}, issn = {1422-0067}, support = {01KI20343//Federal Ministry of Education and Research/ ; }, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; Spike Glycoprotein, Coronavirus ; Pandemics ; Antibodies, Viral ; Viral Envelope Proteins/genetics ; Antibodies, Neutralizing ; Vaccination ; }, abstract = {The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection.}, } @article {pmid36292338, year = {2022}, author = {Manukyan, P and Deviaterikova, A and Velichkovsky, BB and Kasatkin, V}, title = {The Impact of Mild COVID-19 on Executive Functioning and Mental Health Outcomes in Young Adults.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {10}, pages = {}, pmid = {36292338}, issn = {2227-9032}, support = {212201-2-000//RUDN University Scientific Projects Grant System/ ; }, abstract = {COVID-19 is associated with a range of long-lasting symptoms related to cognitive and psycho-emotional spheres. Even mild cases of the disease can lead to persistent cognitive deficits and deterioration of the psycho-emotional state. The purpose of our study was to examine the presence and frequency of psycho-emotional disorders and cognitive deficits in students who recovered from mild form of COVID-19. A total of 40 COVID-19 survivors and 25 healthy controls participated in our study. We assessed three core cognitive functions (inhibition, working memory, task-switching), reaction time and motor speed. We also assessed depression, anxiety and fatigue with self-report questionnaires. The COVID-19 group manifested increased depression and decreased inhibition in comparison with the controls. Our results show that even in young adults who have recovered from mild COVID-19, there are persisting cognitive and psycho-emotional deficits.}, } @article {pmid36292286, year = {2022}, author = {Jegal, KH and Yoon, J and Kim, S and Jang, S and Jin, YH and Lee, JH and Choi, SM and Kim, TH and Kwon, S}, title = {Herbal Medicines for Post-Acute Sequelae (Fatigue or Cognitive Dysfunction) of SARS-CoV-2 Infection: A Phase 2 Pilot Clinical Study Protocol.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {10}, pages = {}, pmid = {36292286}, issn = {2227-9032}, support = {KSN2022220//Korea Institute of Oriental Medicine/ ; }, abstract = {Long-term sequelae refer to persistent symptoms or signs for >6 months after SARS-CoV-2 infection. The most common symptoms of sequelae are fatigue and neuropsychiatric symptoms (concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression). However, approved treatments have not been fully established. Herbal medicines are administered for 12 weeks to patients who continuously complain of fatigue or cognitive dysfunction for >4 weeks that only occurred after COVID-19 diagnoses. Based on the Korean Medicine syndrome differentiation diagnosis, patients with fatigue will be administered Bojungikgi-tang or Kyungok-go, whereas those with cognitive dysfunction will be administered Cheonwangbosim-dan. Results could support evidence that herbal medicines may mitigate fatigue and cognitive dysfunction caused by COVID-19. Furthermore, by investigating the effects of herbal medicines on changes in metabolite and immune response due to COVID-19, which may be responsible for sequelae, the potential of herbal medicines as one of the therapeutic interventions for post-acute sequelae of SARS-CoV-2 infection can be evaluated. Therefore, the effects of herbal medicine on fatigue and cognitive dysfunction sequelae due to COVID-19 will be elucidated in this study to provide an insight into the preparation of medical management for the post-acute sequelae of SARS-CoV-2 infection.}, } @article {pmid36292191, year = {2022}, author = {Cioboata, R and Nicolosu, D and Streba, CT and Vasile, CM and Olteanu, M and Nemes, A and Gheorghe, A and Calarasu, C and Turcu, AA}, title = {Post-COVID-19 Syndrome Based on Disease Form and Associated Comorbidities.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, pmid = {36292191}, issn = {2075-4418}, abstract = {(1) Background: SARS-CoV-2 has infected more than 97 million people worldwide and caused the death of more than 6 million. (2) Methods: Between 1 October and 31 December 2020, 764 patients diagnosed with SARS-CoV-2 infection were selected based on RT-PCR test results. The following parameters were noted: age, gender, origin, days of hospitalization, COVID-19 experienced form, radiographic imaging features, associated comorbidities, and recommended treatment at discharge. (3) Results: The mean age at the time of COVID-19 infection was 55.2 years for men and 55.3 years for women. There was a similar age distribution among patients, regardless of gender. There was a substantial difference between the average lengths of hospitalization and those with residual symptoms-most patients who reported symptoms after discharge had been admitted with moderately severe forms of illness. Fatigue was the main remaining symptom (36%). (4) Conclusions: In conclusion, to clarify the impact of SARS-CoV-2 infection on patients in the long term, further studies are needed to investigate the elements assessed. Well-designed recovery programs will be needed to effectively manage these patients, with multidisciplinary collaboration and a team of professionals involved in all aspects of post-COVID patient health.}, } @article {pmid36291562, year = {2022}, author = {Goh, GK and Dunker, AK and Foster, JA and Uversky, VN}, title = {A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation.}, journal = {Biomolecules}, volume = {12}, number = {10}, pages = {}, pmid = {36291562}, issn = {2218-273X}, mesh = {Humans ; Animals ; *SARS-CoV-2 ; *COVID-19 ; Pangolins ; Phylogeny ; Reproducibility of Results ; Viral Proteins ; Nucleocapsid Proteins/genetics ; Membrane Proteins ; }, abstract = {The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID-percentage of intrinsic disorder-of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PIDN as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal-oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles.}, } @article {pmid36291381, year = {2022}, author = {Morello, R and De Rose, C and Cardinali, S and Valentini, P and Buonsenso, D}, title = {Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {36291381}, issn = {2227-9067}, abstract = {Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia. Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract. In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.}, } @article {pmid36291297, year = {2022}, author = {Pacho-Hernández, JC and Fernández-de-Las-Peñas, C and Fuensalida-Novo, S and Jiménez-Antona, C and Ortega-Santiago, R and Cigarán-Mendez, M}, title = {Sleep Quality Mediates the Effect of Sensitization-Associated Symptoms, Anxiety, and Depression on Quality of Life in Individuals with Post-COVID-19 Pain.}, journal = {Brain sciences}, volume = {12}, number = {10}, pages = {}, pmid = {36291297}, issn = {2076-3425}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; }, abstract = {A better understanding of biological and emotional variables associated with health-related quality of life in people with long-COVID is needed. Our aim was to identify potential direct and indirect effects on the relationships between sensitization-associated symptoms, mood disorders such as anxiety/depressive levels, and sleep quality on health-related quality of life in people suffering from post-COVID-19 pain. One hundred and forty-six individuals who were hospitalized due to COVID-19 during the first wave of the pandemic and suffering from long-term post-COVID-19 pain completed different patient-reported outcome measures (PROMs), including clinical features, symptoms associated with sensitization of the central nervous system (Central Sensitization Inventory), mood disorders (Hospital Anxiety and Depressive Scale), sleep quality (Pittsburgh Sleep Quality Index), and health-related quality of life (paper-based five-level version of EuroQol-5D) in a face-to-face interview conducted at 18.8 (SD 1.8) months after hospitalization. Different mediation models were conducted to assess the direct and indirect effects of the associations among the different variables. The mediation models revealed that sensitization-associated symptoms and depressive levels directly affected health-related quality of life; however, these effects were not statistically significant when sleep quality was included. In fact, the effect of sensitization-associated symptomatology on quality of life (β = -0.10, 95% CI -0.1736, -0.0373), the effect of depressive levels on quality of life (β= -0.09, 95% CI -0.1789, -0.0314), and the effect of anxiety levels on quality of life (β = -0.09, 95% CI -0.1648, -0.0337) were all indirectly mediated by sleep quality. This study revealed that sleep quality mediates the relationship between sensitization-associated symptoms and mood disorders (depressive/anxiety levels) with health-related quality of life in individuals who were hospitalized with COVID-19 at the first wave of the pandemic and reporting post-COVID-19 pain. Longitudinal studies will help to determine the clinical implications of these findings.}, } @article {pmid36291027, year = {2022}, author = {Cherusseri, J and Savio, CM and Khalid, M and Chaudhary, V and Numan, A and Varma, SJ and Menon, A and Kaushik, A}, title = {SARS-CoV-2-on-Chip for Long COVID Management.}, journal = {Biosensors}, volume = {12}, number = {10}, pages = {}, pmid = {36291027}, issn = {2079-6374}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/diagnosis ; COVID-19 Testing ; Point-of-Care Systems ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a "wicked evil" in this century due to its extended progression and huge human mortalities. Although the diagnosis of SARS-CoV-2 viral infection is made simple and practical by employing reverse transcription polymerase chain reaction (RT-PCR) investigation, the process is costly, complex, time-consuming, and requires experts for testing and the constraints of a laboratory. Therefore, these challenges have raised the paradigm of on-site portable biosensors on a single chip, which reduces human resources and enables remote access to minimize the overwhelming burden on the existing global healthcare sector. This article reviews the recent advancements in biosensors for long coronavirus disease (COVID) management using a multitude of devices, such as point-of-care biosensors and lab-on-chip biosensors. Furthermore, it details the shift in the paradigm of SARS-CoV-2-on-chip biosensors from the laboratory to on-site detection with intelligent and economical operation, representing near-future diagnostic technologies for public health emergency management.}, } @article {pmid36289827, year = {2022}, author = {Fernández-de-Las-Peñas, C and Nijs, J and Neblett, R and Polli, A and Moens, M and Goudman, L and Shekhar Patil, M and Knaggs, RD and Pickering, G and Arendt-Nielsen, L}, title = {Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition.}, journal = {Biomedicines}, volume = {10}, number = {10}, pages = {}, pmid = {36289827}, issn = {2227-9059}, support = {LONG COVID EXP//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.}, } @article {pmid36288726, year = {2022}, author = {Monje, M and Iwasaki, A}, title = {The neurobiology of long COVID.}, journal = {Neuron}, volume = {110}, number = {21}, pages = {3484-3496}, pmid = {36288726}, issn = {1097-4199}, support = {U19 CA264504/CA/NCI NIH HHS/United States ; R01 CA258384/CA/NCI NIH HHS/United States ; DP1 NS111132/NS/NINDS NIH HHS/United States ; R01 NS092597/NS/NINDS NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; R01 CA263500/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Nervous System Diseases ; *Mental Disorders ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 and represent a major component of the post-acute COVID-19 syndrome, also known as long COVID. Here, we review what is understood about the pathobiology of post-acute COVID-19 impact on the CNS and discuss possible neurobiological underpinnings of the cognitive symptoms affecting COVID-19 survivors. We propose the chief mechanisms that may contribute to this emerging neurological health crisis.}, } @article {pmid36288615, year = {2022}, author = {Rola, P and Włodarczak, A and Włodarczak, S and Kędzierska, M and Furtan, Ł and Barycki, M and Szudrowicz, M and Kulczycki, JJ and Doroszko, A and Lesiak, M}, title = {Invasive assessment of coronary microvascular dysfunction in patients with long COVID: Outcomes of a pilot study.}, journal = {Kardiologia polska}, volume = {80}, number = {12}, pages = {1252-1255}, doi = {10.33963/KP.a2022.0239}, pmid = {36288615}, issn = {1897-4279}, mesh = {Humans ; Pilot Projects ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Myocardial Ischemia ; *Coronary Artery Disease ; Coronary Circulation ; Coronary Vessels ; }, } @article {pmid36286219, year = {2022}, author = {Azzolino, D and Spolidoro, GCI and Mazzocchi, A and Agostoni, C and Cesari, M}, title = {When the Pandemic Will Be Over: Lots of Hope and Some Concerns.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {7}, number = {5}, pages = {}, pmid = {36286219}, issn = {2308-3417}, abstract = {The COVID-19 pandemic significantly threatened healthcare systems worldwide. The worst-hit population has been represented by older people with underlying chronic comorbidities, while children and adolescents developed mild or asymptomatic forms of the disease. However, certain medical conditions (i.e., obesity, respiratory, or neurological or immune disorders) may increase the risk for poor health outcomes even in young and middle-aged people. Beyond the direct negative effects of the infection, the pandemic posed several health challenges through an increase in psycho-social issues (i.e., anxiety, depression, fatigue, sleep alterations, loneliness, reduced assistance, and loss of income). Accordingly, the pandemic is negatively impacting the accumulation of the functional reserves of each individual, starting from early life. With the long-term effects of the pandemic to be seen in the coming years, clinicians must be prepared to manage such high clinical complexity of people they encounter, through the implementation of multidimensional and multidisciplinary interventions.}, } @article {pmid36285549, year = {2022}, author = {Faghy, MA and Owen, R and Thomas, C and Yates, J and Ferraro, FV and Skipper, L and Barley-McMullen, S and Brown, DA and Arena, R and Ashton, RE}, title = {Is long COVID the next global health crisis?.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {03067}, pmid = {36285549}, issn = {2047-2986}, mesh = {Humans ; *COVID-19 ; Global Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36283919, year = {2023}, author = {Lai, CC and Hsu, CK and Yen, MY and Lee, PI and Ko, WC and Hsueh, PR}, title = {Long COVID: An inevitable sequela of SARS-CoV-2 infection.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {56}, number = {1}, pages = {1-9}, pmid = {36283919}, issn = {1995-9133}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Lung ; Disease Progression ; }, abstract = {At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although more than 98% of patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive acute COVID, a significant portion of survivors can develop residual health problems, which is termed as long COVID. Although severe COVID-19 is generally associated with a high risk of long COVID, patients with asymptomatic or mild disease can also show long COVID. The definition of long COVID is inconsistent and its clinical manifestations are protean. In addition to general symptoms, such as fatigue, long COVID can affect many organ systems, including the respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, and metabolic systems. Moreover, patients with long COVID may experience exercise intolerance and impaired daily function and quality of life. Long COVID may be caused by SARS-CoV-2 direct injury or its associated immune/inflammatory response. Assessment of patients with long COVID requires comprehensive evaluation, including history taking, physical examination, laboratory tests, radiography, and functional tests. However, there is no known effective treatment for long COVID. Based on the limited evidence, vaccines may help to prevent the development of long COVID. As long COVID is a new clinical entity that is constantly evolving, there are still many unknowns, and further investigation is warranted to enhance our understanding of this disease.}, } @article {pmid36282267, year = {2022}, author = {Suran, M}, title = {VA Guidebook on Long COVID.}, journal = {JAMA}, volume = {328}, number = {16}, pages = {1580}, doi = {10.1001/jama.2022.15484}, pmid = {36282267}, issn = {1538-3598}, mesh = {Humans ; *COVID-19 ; Practice Guidelines as Topic ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36282136, year = {2022}, author = {Munblit, D and Greenhawt, M and Brough, HA and Pushkareva, A and Karimova, D and Demidova, A and Warner, JO and Kalayci, O and Sediva, A and Untersmayr, E and Rodriguez Del Rio, P and Vazquez-Ortiz, M and Arasi, S and Alvaro-Lozano, M and Tsabouri, S and Galli, E and Beken, B and Eigenmann, PA}, title = {Allergic diseases and immunodeficiencies in children, lessons learnt from COVID-19 pandemic by 2022: A statement from the EAACI-section on pediatrics.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {33}, number = {10}, pages = {e13851}, pmid = {36282136}, issn = {1399-3038}, mesh = {Child ; Humans ; *COVID-19/epidemiology ; Pandemics ; *Hypersensitivity ; *Asthma/epidemiology ; *Immunologic Deficiency Syndromes ; Post-Acute COVID-19 Syndrome ; }, abstract = {By the April 12, 2022, the COVID-19 pandemic had resulted in over half a billion people being infected worldwide. There have been 6.1 million deaths directly due to the infection, but the pandemic has had many more short- and long-term pervasive effects on the physical and mental health of the population. Allergic diseases are among the most prevalent noncommunicable chronic diseases in the pediatric population, and health-care professionals and researchers were seeking answers since the beginning of pandemic. Children are at lower risk of developing severe COVID-19 or dying from infection. Allergic diseases are not associated with a higher COVID-19 severity and mortality, apart from severe/poorly controlled asthma. The pandemic disrupted routine health care, but many mitigation strategies, including but not limited to telemedicine, were successfully implemented to continue delivery of high-standard care. Although children faced a multitude of pandemic-related issues, allergic conditions were effectively treated remotely while reduction in air pollution and lack of contact with outdoor allergens resulted in improvement, particularly respiratory allergies. There is no evidence to recommend substantial changes to usual management modalities of allergic conditions in children, including allergen immunotherapy and use of biologicals. Allergic children are not at greater risk of multisystem inflammatory syndrome development, but some associations with Long COVID were reported, although the data are limited, and further research is needed. This statement of the EAACI Section on Pediatrics provides recommendations based on the lessons learnt from the pandemic, as available evidence.}, } @article {pmid36282031, year = {2022}, author = {Mendola, M and Leoni, M and Cozzi, Y and Manzari, A and Tonelli, F and Metruccio, F and Tosti, L and Battini, V and Cucchi, I and Costa, MC and Carrer, P}, title = {Long-term COVID symptoms, work ability and fitness to work in healthcare workers hospitalized for Sars-CoV-2 infection.}, journal = {La Medicina del lavoro}, volume = {113}, number = {5}, pages = {e2022040}, pmid = {36282031}, issn = {0025-7818}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Work Capacity Evaluation ; Health Personnel ; Dyspnea/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: COVID-19 can affect the persistence of symptoms and work ability (WA), hence the fitness to work of healthcare workers (HCW). We describe the effects of COVID-19 in hospitalized HCWs of a large Hospital in Lombardy and their implications on WA and fitness to work.

METHODS: Fifty-six HCWs of Fatebenefratelli-Sacco Hospital have been hospitalized for COVID-19 since March 2020. Clinical and fitness-to-work data were acquired from Occupational Health Surveillance Program. A structured questionnaire was administered to 53/56 HCWs 18 months after infection to investigate Long-COVID symptoms and WA.

RESULTS: Symptoms most reported at recovery (rhino-pharyngeal swab-NPS-negative) were exertional dyspnea (86.8%), asthenia (86.8%), arthro-myalgia (71.7%), sleep disorders (64.2%), resting dyspnea (62.3%), cough (56.6%). 69.6% underwent evaluation at out-patient clinics experienced in Long-COVID. Ten months after recovery, symptoms related to physical well-being decreased while memory and anxiety/depression were more persistent. At recovery, the WA score decreased from 10 to 8, and then an improvement from 8 to 9 was noted during the survey. At the return-to-work examination, fit-to-work judgements with restrictions increased from 31.4% to 58.7%; then, a slight decrease in the rate of judgements with restrictions was observed at the survey's time.

CONCLUSION: Post-COVID-19 symptoms can persist for a long time and could impact WA and fitness-to-work of HCW. Adequate health surveillance protocols should guarantee the health protection of HCW with persistent disorders after COVID-19.}, } @article {pmid36281870, year = {2024}, author = {Hon, KLE and Leung, AKC and Leung, KKY and Wong, AHC}, title = {Impact of "Long Covid" on Children: Global and Hong Kong Perspectives.}, journal = {Current pediatric reviews}, volume = {20}, number = {1}, pages = {59-65}, doi = {10.2174/1573396319666221021154949}, pmid = {36281870}, issn = {1875-6336}, mesh = {Adolescent ; Child ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Hong Kong/epidemiology ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease (COVID-19) pandemic spares no nation or city, and the virus is responsible for the escalating incidence and mortality worldwide.

OBJECTIVE: This article reviews the impact of "Long Covid" on Children.

METHODS: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "COVID-19" OR "long COVID". The search was restricted to children and adolescent aged < 18 years and English literature.

RESULTS: Many large-scale studies have provided strong scientific evidence as to the detrimental and irreversible sequelae of COVID-19 on the health, psychology, and development of affected children. Many insights into managing this disease can be obtained from comparing the management of influenza. COVID-19 is generally a mild respiratory disease in children. Several syndromes, such as multisystem inflammatory syndrome in children (MIS-C) and COVID toe, are probably not specific to SARS-CoV-2. "Long COVID", or the long-term effects of SARS-CoV-2 infection, or the prolonged isolation and containment strategies on education and psychosocial influences on children associated with the pandemic, are significant.

CONCLUSION: Healthcare providers must be aware of the potential effects of quarantine on children's mental health. More importantly, healthcare providers must appreciate the importance of the decisions and actions made by governments, non-governmental organizations, the community, schools, and parents in reducing the possible effects of this situation. Multifaceted age-specific and developmentally appropriate strategies must be adopted by healthcare authorities to lessen the negative impact of quarantine on the psychological well-being of children.}, } @article {pmid36281239, year = {2022}, author = {Pink, I and Welte, T}, title = {[Not Available].}, journal = {Pneumo news}, volume = {14}, number = {5}, pages = {43-49}, pmid = {36281239}, issn = {2199-3866}, } @article {pmid36280755, year = {2023}, author = {Al-Hakeim, HK and Al-Rubaye, HT and Al-Hadrawi, DS and Almulla, AF and Maes, M}, title = {Long-COVID post-viral chronic fatigue and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study.}, journal = {Molecular psychiatry}, volume = {28}, number = {2}, pages = {564-578}, pmid = {36280755}, issn = {1476-5578}, mesh = {Humans ; Antioxidants ; *Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Affective Symptoms ; *COVID-19 ; Oxidative Stress/physiology ; Inflammation ; Zinc ; }, abstract = {The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety symptoms 3-4 months later. The present study was performed to examine the effects of SpO2 and PBT during acute infection on immune, oxidative and nitrosative stress (IO&NS) pathways and neuropsychiatric symptoms of Long COVID. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the neuropsychiatric symptoms of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Lowered SpO2 strongly predicts OSTOX/ANTIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. The results suggest that post-viral somatic and mental symptoms have a neuroimmune and neuro-oxidative origin.}, } @article {pmid36280088, year = {2022}, author = {Ferreira, LC and Gomes, CEM and Rodrigues-Neto, JF and Jeronimo, SMB}, title = {Genome-wide association studies of COVID-19: Connecting the dots.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {106}, number = {}, pages = {105379}, pmid = {36280088}, issn = {1567-7257}, mesh = {Humans ; *COVID-19/genetics ; SARS-CoV-2/genetics ; Genome-Wide Association Study ; Post-Acute COVID-19 Syndrome ; Antiviral Agents ; Membrane Transport Proteins ; }, abstract = {Genome-wide association studies (GWASs) are a research approach used to identify genetic variants associated with common diseases, like COVID-19. The lead genetic variants (n = 41) reported by the eleven largest COVID-19 GWASs are mapped to 22 different chromosomal regions. The loci 3q21.31 (LZTFL1 and chemokine receptor genes) and 9q34.2 (ABO), associated with disease severity and susceptibility to infection, respectively, were the most replicated findings across studies. Genes involved with mucociliary clearance (CEP97, FOXP4), viral-entry (ACE2, SLC6A20) and mucosal immunity (MIR6891) are associated with the risk of SARS-CoV-2 infection while genes of antiviral immune response (IFNAR2, OAS1), leukocyte trafficking (CCR9, CXCR6) and lung injury (DPP9, NOTCH4) are associated with severe disease. The biological processes underlying the risk of infection occur prominently, but not exclusively, in the upper airways whereas the severe COVID-19-associated processes in alveolar-capillary interface. The COVID-19 GWASs has unraveled key genetic mechanisms of SARS-CoV-2 pathogenesis, although the genetic basis of other COVID-19 related phenotypes (long COVID and neurological impairment) remains to be elucidated.}, } @article {pmid36278147, year = {2022}, author = {Rudofker, EW and Parker, H and Cornwell, WK}, title = {An Exercise Prescription as a Novel Management Strategy for Treatment of Long COVID.}, journal = {JACC. Case reports}, volume = {4}, number = {20}, pages = {1344-1347}, pmid = {36278147}, issn = {2666-0849}, support = {UL1 TR002535/TR/NCATS NIH HHS/United States ; }, abstract = {Mechanisms causing the post-acute sequelae of SARS-CoV-2 (long COVID) remain elusive, but the clinical phenotype is consistent with cardiac deconditioning. We report a case series of patients with long COVID whose symptoms improved/resolved with exercise and present exercise training as a novel therapeutic strategy for management of long COVID syndrome. (Level of Difficulty: Intermediate.).}, } @article {pmid36275692, year = {2022}, author = {Goh, D and Lim, JCT and Fernaíndez, SB and Joseph, CR and Edwards, SG and Neo, ZW and Lee, JN and Caballero, SG and Lau, MC and Yeong, JPS}, title = {Corrigendum: Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1036894}, doi = {10.3389/fimmu.2022.1036894}, pmid = {36275692}, issn = {1664-3224}, abstract = {[This corrects the article DOI: 10.3389/fimmu.2022.939989.].}, } @article {pmid36274177, year = {2022}, author = {Salari, N and Khodayari, Y and Hosseinian-Far, A and Zarei, H and Rasoulpoor, S and Akbari, H and Mohammadi, M}, title = {Global prevalence of chronic fatigue syndrome among long COVID-19 patients: A systematic review and meta-analysis.}, journal = {BioPsychoSocial medicine}, volume = {16}, number = {1}, pages = {21}, pmid = {36274177}, issn = {1751-0759}, abstract = {BACKGROUND: Chronic fatigue syndrome is a persistent and debilitating disorder. According to several studies, chronic fatigue syndrome has been identified among recovered COVID-19 patients as the most common symptom of long COVID. The aim of this systematic review and meta-analysis study was to obtain the prevalence of chronic fatigue syndrome in long COVID cases.

METHODS: In this systematic review and meta-analysis, we analysed reported results of studies that assessed the occurrence of chronic fatigue syndrome among COVID-19 patients four weeks after the onset of symptoms. The study selection was commenced by searching PubMed, Web of Science, Science Direct, Scopus, Embase, and Google scholar using the keywords of Chronic fatigue syndrome, COVID-19, and post-COVID-19 syndrome. The searches were without a lower time limit and until April 2022. Heterogeneity of studies was assessed using the I[2] index, and a random effects model was used for analysis. Data analysis was performed within the Comprehensive Meta-Analysis software (version 2).

RESULTS: The pooled prevalence of chronic fatigue syndrome four weeks after the onset of COVID-19 symptoms, in 52 studies with a sample size of 127,117, was 45.2% (95% CI: 34.1-56.9%). Meta-regression analysis in examining the effects of the two factors of sample size, and year of study on the changes in the overall prevalence, showed that with increasing sample size, and year of study, the prevalence of chronic fatigue syndrome among long COVID patients (p < 0.05).

CONCLUSION: Our results show that the overall prevalence of chronic fatigue syndrome as a long COVID symptom is 45.2%. Chronic fatigue after infection with COVID-19 can negatively affect personal and social lives. Given such significant negative consequences caused by the syndrome, it is recommended that health policymakers allocate funds to reduce the adverse effects of this syndrome, by creating programs to support long COVID patients.}, } @article {pmid36273799, year = {2023}, author = {Golla, R and Vuyyuru, S and Kante, B and Kumar, P and Thomas, DM and Makharia, G and Kedia, S and Ahuja, V}, title = {Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {21}, number = {3}, pages = {789-796.e1}, pmid = {36273799}, issn = {1542-7714}, mesh = {Humans ; *Dyspepsia/diagnosis ; Follow-Up Studies ; Prospective Studies ; *COVID-19/complications ; *Gastrointestinal Diseases/diagnosis ; *Irritable Bowel Syndrome/complications ; Disease Progression ; *Malabsorption Syndromes ; }, abstract = {BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19.

METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI.

RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01).

CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.}, } @article {pmid36272444, year = {2023}, author = {Sacks-Zimmerman, A and Bergquist, TF and Farr, EM and Cornwell, MA and Kanellopoulos, D}, title = {Rehabilitation of Neuropsychiatric Symptoms in Patients With Long COVID: Position Statement.}, journal = {Archives of physical medicine and rehabilitation}, volume = {104}, number = {2}, pages = {350-354}, pmid = {36272444}, issn = {1532-821X}, mesh = {Adult ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Quality of Life ; *Mental Disorders ; Chronic Disease ; }, abstract = {Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.}, } @article {pmid36271437, year = {2023}, author = {Moslemi, C and Saekmose, S and Larsen, R and Brodersen, T and Didriksen, M and Hjalgrim, H and Banasik, K and Nielsen, KR and Bruun, MT and Dowsett, J and Kasperen, KA and Mikkelsen, S and Hansen, TF and Ullum, H and Erikstrup, C and Olsson, ML and Ostrowski, SR and Pedersen, OB}, title = {A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19.}, journal = {Transfusion}, volume = {63}, number = {1}, pages = {47-58}, pmid = {36271437}, issn = {1537-2995}, mesh = {Humans ; ABO Blood-Group System ; *Blood Group Antigens/genetics ; Cohort Studies ; *COVID-19/blood/genetics ; *Post-Acute COVID-19 Syndrome/blood/genetics ; SARS-CoV-2 ; Genetic Predisposition to Disease ; }, abstract = {BACKGROUND: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well.

STUDY DESIGN AND METHODS: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates.

RESULTS: The Lewis blood group antigen Le[a] displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79-0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06-1.14] p < .001, 1.17 CI[1.14-1.2] p < .001, and 1.2 CI[1.14-1.26] p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found.

DISCUSSION: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Le[a] and confirms the previous link to blood group O. The new association to Le[a] could be explained by a link between mucosal microbiome and SARS-CoV-2.}, } @article {pmid36271419, year = {2022}, author = {Hultström, M and Lipcsey, M and Morrison, DR and Nakanishi, T and Butler-Laporte, G and Chen, Y and Yoshiji, S and Forgetta, V and Farjoun, Y and Wallin, E and Larsson, IM and Larsson, A and Marton, A and Titze, JM and Nihlén, S and Richards, JB and Frithiof, R}, title = {Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19: a multicenter cohort study.}, journal = {Critical care (London, England)}, volume = {26}, number = {1}, pages = {322}, pmid = {36271419}, issn = {1466-609X}, support = {KAW 2020.0182//Knut och Alice Wallenbergs Stiftelse/ ; 20210089, 20190639, 20190637//Hjärt-Lungfonden/ ; SLS-938101//Svenska Läkaresällskapet/ ; CIHR: 365825//CIHR/Canada ; 2014-02569, 2014-07606//Vetenskapsrådet/ ; F2020-0054//Swedish Kidney Foundation/ ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Dehydration/etiology ; Sodium ; Urea ; Potassium ; Amino Acids ; Glucose ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19.

METHODS: The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental.

RESULTS: Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern.

CONCLUSIONS: Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID.

TRIAL REGISTRATION: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).}, } @article {pmid36270117, year = {2022}, author = {Gupta, A and Satapathy, AK and Bahinipati, P}, title = {Delayed catastrophic thrombotic events in post-acute COVID-19.}, journal = {Thrombosis research}, volume = {220}, number = {}, pages = {60-64}, pmid = {36270117}, issn = {1879-2472}, mesh = {Humans ; *COVID-19/complications ; *Thrombosis/etiology ; Anticoagulants ; }, } @article {pmid36268783, year = {2022}, author = {Inal, J and Paizuldaeva, A and Terziu, E}, title = {Therapeutic use of calpeptin in COVID-19 infection.}, journal = {Clinical science (London, England : 1979)}, volume = {136}, number = {20}, pages = {1439-1447}, pmid = {36268783}, issn = {1470-8736}, mesh = {Humans ; Calpain ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {This perspective considers the benefits of the potential future use of the cell permeant calpain inhibitor, calpeptin, as a drug to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent work has reported calpeptin's capacity to inhibit entry of the virus into cells. Elsewhere, several drugs, including calpeptin, were found to be able to inhibit extracellular vesicle (EV) biogenesis. Unsurprisingly, because of similarities between viral and EV release mechanisms, calpeptin has also been shown to inhibit viral egress. This approach, identifying calpeptin, through large-scale screening studies as a candidate drug to treat COVID-19, however, has not considered the longer term likely benefits of calpain inhibition, post-COVID-19. This perspective will reflect on the capacity of calpeptin for treating long COVID by inhibiting the overproduction of neutrophil extracellular traps potentially damaging lung cells and promoting clotting, together with limiting associated chronic inflammation, tissue damage and pulmonary fibrosis. It will also reflect on the tolerated and detrimental in vivo side-effects of calpain inhibition from various preclinical studies.}, } @article {pmid36268261, year = {2022}, author = {Dal Negro, RW and Turco, P and Povero, M}, title = {Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause.}, journal = {Multidisciplinary respiratory medicine}, volume = {17}, number = {1}, pages = {875}, pmid = {36268261}, issn = {1828-695X}, abstract = {BACKGROUND: During SARS-CoV-2 infection, diffuse alveolar damage and pulmonary microvascular abnormalities are critical events that result in gas exchange disorders of varying severity and duration. The only measure of carbon monoxide (CO) diffusing capacity (DLCO) is unable to distinguish the alveolar from the vascular side of present and residual diffusive abnormalities, and measure of nitric oxide (NO) diffusing capacity (DLNO) is also recommended. Dyspnoea, despite being understudied, persists in a significant proportion of patients for several weeks after hospital discharge. The goal of this study was to look into the underlying cause of long-term dyspnoea in patients who were "clinically and radiologically recovered" from COVID pneumonia by assessing DLCO and DLNO at the same time.

METHODS: Patients of both genders, aged ≥18 years, who had a CT scan showing complete resolution of COVID-related parenchymal lesions were recruited consecutively. Spirometrical volumes, blood haemoglobin, SpO2, DLCO, DLNO and capillary blood volume (Vc) were measured. Data from patients without dyspnoea (group A) and from patients still claiming dyspnoea after 12-16 weeks from their hospital discharge (group B) were statistically compared.

RESULTS: Forty patients were recruited: 19 in group A and 21 in group B. Groups were comparable for their general characteristics and spirometrical volumes, that were in the normal range. Mean values for DLCO, DLNO and Vc were significantly and substantially lower than predicted only in patients of group B (p<0.011; p<0.0036; p<0.02; p<0.001, respectively). The DLNO/ DLCO ratio was higher in group B (p<0.001) and inversely correlated to Vc values (-0.3636).

CONCLUSIONS: The single-breath, simultaneous measurement of DLCO, DLNO, and Vc demonstrated that problems with blood gas exchange can persist even after parenchymal lesions have healed completely. Regardless of the normality of spirometric volumes, there was a significant reduction in lung capillary blood volume. In these patients, the cause of long-term dyspnoea may be related to hidden abnormalities in the vascular side of diffusive function. In the near future, novel therapeutic approaches against residual and symptomatic signs of long-COVID are possible.}, } @article {pmid36267244, year = {2022}, author = {Goldhaber, NH and Ogan, WS and Greaves, A and Tai-Seale, M and Sitapati, A and Longhurst, CA and Horton, LE}, title = {Population-Based Evaluation of Postacute Coronavirus Disease-2019 (COVID-19) Chronic Sequelae in Patients Who Tested Positive for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).}, journal = {Open forum infectious diseases}, volume = {9}, number = {10}, pages = {ofac495}, pmid = {36267244}, issn = {2328-8957}, abstract = {The true incidence and comprehensive characteristics of Long Coronavirus Disease-19 (COVID-19) are currently unknown. This is the first population-based outreach study of Long COVID within an entire health system, conducted to determine operational needs to care for patients with Long COVID.}, } @article {pmid36267023, year = {2024}, author = {Lutaud, R and Verger, P and Peretti-Watel, P and Eldin, C}, title = {When the patient is making the (wrong?) diagnosis: a biographical approach to patients consulting for presumed Lyme disease.}, journal = {Family practice}, volume = {41}, number = {4}, pages = {534-542}, pmid = {36267023}, issn = {1460-2229}, support = {//IHU Méditerranée Infection/ ; ANR-10-AHU-03//National Research Agency/ ; //Region Provence Alpes Côte d'Azur and European funding "FEDER PIRMI."/ ; }, mesh = {Humans ; *Lyme Disease/diagnosis ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Referral and Consultation ; Aged ; COVID-19/diagnosis ; Diagnostic Errors ; France ; }, abstract = {BACKGROUND: Media coverage of Lyme disease (LD) has led to an increase in consultations for presumed LD in Europe. However, LD is confirmed in only 10%-20% of patients, with a significant number remaining in a diagnostic dead-end.

OBJECTIVES: To reach a deeper understanding of how patients themselves contribute to the diagnostic process. To describe the genesis of the LD hypothesis in care pathways.

METHODS: In 2019, 30 patients from a prospective cohort consulting in the infectious diseases department at University Hospital in Marseille for presumed LD were recruited for semistructured interviews. The inclusion criteria were: suffering from subjective symptoms for 6 months, no clinical or paraclinical argument suggesting current LD. The patients' medical trajectories were collected using a biographical approach.

RESULTS: The diagnosis of LD was primarily triggered by identification with personal testimonies found on the Internet. Most of patients were leading their own diagnostic investigation. The majority of participants were convinced they had LD despite the lack of medical evidence and the scepticism of their referring GP.

CONCLUSION: GPs should first systematically explore patients' aetiologic representations in order to improve adherence to the diagnosis especially in the management of medically unexplained symptoms. Long COVID-19 syndrome challenge offers an opportunity to promote active patient involvement in diagnosis.}, } @article {pmid36265876, year = {2022}, author = {Greenhalgh, T and Sivan, M and Delaney, B and Evans, R and Milne, R}, title = {Authors' reply to Ward.}, journal = {BMJ (Clinical research ed.)}, volume = {379}, number = {}, pages = {o2506}, doi = {10.1136/bmj.o2506}, pmid = {36265876}, issn = {1756-1833}, } @article {pmid36263014, year = {2022}, author = {Yin, Y and Liu, XZ and Tian, Q and Fan, YX and Ye, Z and Meng, TQ and Wei, GH and Xiong, CL and Li, HG and He, X and Zhou, LQ}, title = {Transcriptome and DNA methylome analysis of peripheral blood samples reveals incomplete restoration and transposable element activation after 3-months recovery of COVID-19.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {1001558}, pmid = {36263014}, issn = {2296-634X}, abstract = {Comprehensive analyses showed that SARS-CoV-2 infection caused COVID-19 and induced strong immune responses and sometimes severe illnesses. However, cellular features of recovered patients and long-term health consequences remain largely unexplored. In this study, we collected peripheral blood samples from nine recovered COVID-19 patients (median age of 36 years old) from Hubei province, China, 3 months after discharge as well as 5 age- and gender-matched healthy controls; and carried out RNA-seq and whole-genome bisulfite sequencing to identify hallmarks of recovered COVID-19 patients. Our analyses showed significant changes both in transcript abundance and DNA methylation of genes and transposable elements (TEs) in recovered COVID-19 patients. We identified 425 upregulated genes, 214 downregulated genes, and 18,516 differentially methylated regions (DMRs) in total. Aberrantly expressed genes and DMRs were found to be associated with immune responses and other related biological processes, implicating prolonged overreaction of the immune system in response to SARS-CoV-2 infection. Notably, a significant amount of TEs was aberrantly activated and their activation was positively correlated with COVID-19 severity. Moreover, differentially methylated TEs may regulate adjacent gene expression as regulatory elements. Those identified transcriptomic and epigenomic signatures define and drive the features of recovered COVID-19 patients, helping determine the risks of long COVID-19, and guiding clinical intervention.}, } @article {pmid36261892, year = {2022}, author = {}, title = {Clinical Guidelines for Long COVID Await a Better Definition of the Syndrome.}, journal = {The American journal of nursing}, volume = {122}, number = {11}, pages = {13}, doi = {10.1097/01.NAJ.0000897076.99993.50}, pmid = {36261892}, issn = {1538-7488}, mesh = {Humans ; *COVID-19 ; *Guidelines as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {A recent study takes a step in that direction.}, } @article {pmid36261163, year = {2022}, author = {Ward, PW}, title = {Long covid update for primary care should acknowledge functional symptoms.}, journal = {BMJ (Clinical research ed.)}, volume = {379}, number = {}, pages = {o2501}, doi = {10.1136/bmj.o2501}, pmid = {36261163}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36261140, year = {2022}, author = {Berger, M}, title = {Covid-19 and long covid highlight the need to tackle behavioural health challenges.}, journal = {BMJ (Clinical research ed.)}, volume = {379}, number = {}, pages = {o2502}, doi = {10.1136/bmj.o2502}, pmid = {36261140}, issn = {1756-1833}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Psychiatry ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36257950, year = {2022}, author = {Nevalainen, OPO and Horstia, S and Laakkonen, S and Rutanen, J and Mustonen, JMJ and Kalliala, IEJ and Ansakorpi, H and Kreivi, HR and Kuutti, P and Paajanen, J and Parkkila, S and Paukkeri, EL and Perola, M and Pourjamal, N and Renner, A and Rosberg, T and Rutanen, T and Savolainen, J and , and Haukka, JK and Guyatt, GH and Tikkinen, KAO}, title = {Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6152}, pmid = {36257950}, issn = {2041-1723}, mesh = {Humans ; Alanine/therapeutic use ; Antiviral Agents/therapeutic use ; Finland/epidemiology ; Hospitalization ; Quality of Life ; Treatment Outcome ; Randomized Controlled Trials as Topic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.}, } @article {pmid36257307, year = {2022}, author = {August, D and Stete, K and Hilger, H and Götz, V and Biever, P and Hosp, J and Wagner, D and Köhler, TC and Gerstacker, K and Seufert, J and Laubner, K and Kern, W and Rieg, S}, title = {[Complaints and clinical findings six months after COVID-19: outpatient follow-up at the University Medical Center Freiburg].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {76}, number = {10}, pages = {679-688}, doi = {10.1055/a-1916-1405}, pmid = {36257307}, issn = {1438-8790}, mesh = {Male ; Female ; Humans ; *COVID-19 ; SARS-CoV-2 ; Outpatients ; Quality of Life ; Retrospective Studies ; Follow-Up Studies ; Academic Medical Centers ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19. However, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg.

METHODS:  Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19. All patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists.

FINDINGS:  132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60 %) had been treated as outpatients and 53 (40 %) as inpatients. Most common complaints were persistent fatigue (82 %) and dyspnea on exertion (61 %). Further common complaints were impairments of concentration (54 %), insomnia (43 %), and impairments of smell or taste (35 %). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients.

CONCLUSION:  Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.}, } @article {pmid36253950, year = {2024}, author = {Zheng, X and Qian, M and Ye, X and Zhang, M and Zhan, C and Li, H and Luo, T}, title = {Implications for long COVID: A systematic review and meta-aggregation of experience of patients diagnosed with COVID-19.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {40-57}, pmid = {36253950}, issn = {1365-2702}, mesh = {Humans ; Aftercare ; Patient Discharge ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology ; Qualitative Research ; }, abstract = {AIMS AND OBJECTIVES: This review aims to synthesize the available evidence of what patients experience when infected with COVID-19, both in hospital and post-discharge settings.

DESIGN: This review was conducted using the Joanna Briggs Institute (JBI) methodology for qualitative systematic reviews and evidence synthesis. Reporting of results was presented according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a public health crisis worldwide. Many patients diagnosed with COVID-19 have varied levels of persisting mental disorders. Previous studies have reported the degree, prevalence and outcome of psychological problems. Minimal research explored the experience of patients with long COVID. The real-life experience of patients with COVID-19 from diagnosis to post-discharge can deepen the understanding of nurses, physicians and policymakers.

METHODS: All studies describing the experience of patients were included. Two authors independently appraised the methodological quality of the included studies using the JBI Critical Appraisal Checklist for Qualitative Research 2020.

RESULTS: This systematic review aggregated patients' experience of being diagnosed with COVID-19 in both hospitalized and post-discharge settings. Finally, 17 studies met inclusion criteria and quality appraisal guidelines. The selected studies in the meta-synthesis resulted in 12 categories, and further were concluded as five synthesized findings: physical symptoms caused by the virus, positive and negative emotional responses to the virus, positive coping strategies as facilitators of epidemic prevention and control, negative coping strategies as obstacles of epidemic prevention and control, and unmet needs for medical resource.

CONCLUSIONS: The psychological burden of patients diagnosed with COVID-19 is heavy and persistent. Social support is essential in the control and prevention of the epidemic. Nurses and other staff should pay more attention to the mental health of the infected patients both in and after hospitalization.

Nurses should care about the persistent mental trauma of COVID-19 survivors and provide appropriate psychological interventions to mitigate the negative psychological consequences of them. Besides, nurses, as healthcare professionals who may have the most touch with patients, should evaluate the level of social support and deploy it for them. It is also needed for nurses to listen to patient's needs and treat them with carefulness and adequate patience in order to decrease the unmet needs of patients.}, } @article {pmid36253560, year = {2023}, author = {Xu, SW and Ilyas, I and Weng, JP}, title = {Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies.}, journal = {Acta pharmacologica Sinica}, volume = {44}, number = {4}, pages = {695-709}, pmid = {36253560}, issn = {1745-7254}, mesh = {Animals ; Humans ; Biomarkers ; *COVID-19/pathology ; *Endothelial Cells/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.}, } @article {pmid36252983, year = {2022}, author = {McNaughton, CD and Austin, PC and Sivaswamy, A and Fang, J and Abdel-Qadir, H and Daneman, N and Udell, JA and Wodchis, WP and Mostarac, I and Lee, DS and Atzema, CL}, title = {Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {194}, number = {40}, pages = {E1368-E1376}, pmid = {36252983}, issn = {1488-2329}, mesh = {Adult ; Female ; Humans ; Male ; Caregiver Burden ; *COVID-19/complications/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection.

METHODS: We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex.

RESULTS: Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI -0.67 to -0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (-27.31) and outpatient (-0.87) encounters.

INTERPRETATION: We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).}, } @article {pmid36252801, year = {2022}, author = {Santos, CAD and Fonseca Filho, GG and Alves, MM and Macedo, EYL and Pontes, MGA and Paula, AP and Barreto, CTR and Zeneide, FN and Nery, AF and Freitas, RAO and D'Souza-Li, L}, title = {Maternal and Neonatal Outcomes Associated with Mild COVID-19 Infection in an Obstetric Cohort in Brazil.}, journal = {The American journal of tropical medicine and hygiene}, volume = {107}, number = {5}, pages = {1060-1065}, pmid = {36252801}, issn = {1476-1645}, mesh = {Infant, Newborn ; Female ; Pregnancy ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Pandemics ; *Premature Birth/epidemiology ; COVID-19 Testing ; *Depression, Postpartum/epidemiology ; Prospective Studies ; Pregnancy Outcome ; Brazil/epidemiology ; *Pregnancy Complications ; Cohort Studies ; *Infant, Newborn, Diseases/epidemiology ; *Pregnancy Complications, Infectious/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Previous coronavirus epidemics were associated with increased maternal morbidity, mortality, and adverse obstetric outcomes. Reports for SARS-CoV-2 indicate that the obstetric population is at increased risk for severe illness, although there are still limited data on mild COVID-19 infection during pregnancy. To determine the association between mild COVID-19 infection during pregnancy, and maternal and neonatal outcomes, we performed a prospective cohort study among pregnant women with COVID-19 and a control group. Postnatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. We recruited 84 pregnant women with mild COVID-19 and 88 pregnant women without COVID-19. All participants were unvaccinated. The most common acute COVID-19 symptoms were headache (82.1%), loss of smell (81%), and asthenia (77.4%). The median duration of long COVID symptoms was 60 days (interquartile range, 130). Pregnant women with a COVID-19 diagnosis were at greater risk for obstetric ultrasound abnormalities-mainly, fetal growth restriction (relative risk [RR], 12.40; 95% CI, 1.66-92.5), premature birth (RR, 2.62; 95% CI, 1.07-6.43), and postpartum depression (RR, 2.28; 95% CI, 1.24-4.21). Our results alert clinicians to the consequences of COVID-19 during pregnancy, even in mild cases, given the increased risk of ultrasound abnormalities, premature birth, long COVID symptoms, and postpartum depression. National guidelines on preventive measures and treatments should be based on scientific evidence, including attention to the impact on health and family needs during and after the COVID-19 pandemic.}, } @article {pmid36250103, year = {2022}, author = {de Castro, MV and Silva, MVR and Soares, FB and Cória, VR and Naslavsky, MS and Scliar, MO and Castelli, EC and de Oliveira, JR and Sasahara, GL and Santos, KS and Cunha-Neto, E and Kalil, J and Zatz, M}, title = {Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: A case report.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1008585}, pmid = {36250103}, issn = {2296-858X}, abstract = {BACKGROUND: The influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins.

CASE PRESENTATION AND METHODS: Here we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing.

CONCLUSION: Although the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.}, } @article {pmid36250059, year = {2022}, author = {Braga-Paz, I and Ferreira de Araújo, JL and Alves, HJ and de Ávila, RE and Resende, GG and Teixeira, MM and de Aguiar, RS and de Souza, RP and Bahia, D}, title = {Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {905757}, pmid = {36250059}, issn = {2235-2988}, mesh = {*Ageusia/etiology ; Angiotensin-Converting Enzyme 2/*genetics ; Anosmia ; *COVID-19/genetics ; Cognition ; Gene Expression ; Humans ; *Olfaction Disorders/genetics ; Receptors, Angiotensin ; SARS-CoV-2 ; }, abstract = {In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.}, } @article {pmid36249044, year = {2022}, author = {Ballotta, L and Simonetti, O and D'Agaro, P and Segat, L and Koncan, R and Martinez-Orellana, P and Dattola, F and Orsini, E and Marcello, A and Dal Monego, S and Licastro, D and Misin, A and Mohamed, S and Sbisà, E and Lucchini, E and De Sabbata, GM and Zaja, F and Luzzati, R}, title = {Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {945060}, pmid = {36249044}, issn = {2234-943X}, abstract = {Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild-moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.}, } @article {pmid36248863, year = {2022}, author = {Corrêa, HL and Deus, LA and Araújo, TB and Reis, AL and Amorim, CEN and Gadelha, AB and Santos, RL and Honorato, FS and Motta-Santos, D and Tzanno-Martins, C and Neves, RVP and Rosa, TS}, title = {Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1006076}, pmid = {36248863}, issn = {1664-3224}, mesh = {Brazil/epidemiology ; *COVID-19/complications/epidemiology ; Female ; Hand Strength ; Humans ; Interleukin-10 ; Iron ; Male ; Phosphates ; Renal Dialysis/adverse effects/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample.

METHODS: 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m[2]) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05.

RESULTS: We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue.

CONCLUSION: There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial 'U1111-1237-8231'. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.}, } @article {pmid36247234, year = {2022}, author = {Norouzi Masir, M and Shirvaliloo, M}, title = {Symptomatology and microbiology of the gastrointestinal tract in post-COVID conditions.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {6}, number = {10}, pages = {667-676}, pmid = {36247234}, issn = {2397-9070}, abstract = {Post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC), refer to the persistence of symptoms in COVID-19 long-haulers. Various manifestations of post-COVID conditions are general symptoms and/or manifestations of damage in multiple organs. Besides, SARS-CoV-2 can involve the gastrointestinal tract, resulting in sequelae such as diarrhea, abdominal pain, nausea, anorexia, vomiting, constipation, abdominal distension, acid reflux, and/or gastrointestinal bleeding. Previous investigations point to SARS-CoV-2 entry into enterocytes enhances by the angiotensin-converting enzyme 2 (ACE2) receptors. Interestingly, ACE2 receptors are abundantly expressed in the gut, implying infection with SARS-CoV-2 might occur through this route as well as in the respiratory tract. According to mounting evidence, SARS-CoV-2 RNA has been identified in fecal specimens of patients with COVID-19 during and beyond the acute phase. In addition, studies have shown gut microbiome composition is altered in patients with PASC, hence, another putative mechanism linked to gastrointestinal symptoms is gut dysbiosis. The presence of the gut-lung axis in COVID-19 might have major implications for disease pathogenesis and treatment. This review discussed the prevalence of gastrointestinal symptoms and pathophysiology underlying possible infection of the gut in patients with PASC. Also, SARS-COV-2 induced NLRP3 inflammasome-dependent inflammatory pathways are briefly addressed.}, } @article {pmid36247216, year = {2022}, author = {McCracken, LM and Buhrman, M and Badinlou, F and Brocki, KC}, title = {Health, well-being, and persisting symptoms in the pandemic: What is the role of psychological flexibility?.}, journal = {Journal of contextual behavioral science}, volume = {26}, number = {}, pages = {187-192}, pmid = {36247216}, issn = {2212-1447}, abstract = {Finding psychological factors that can reduce the substantial impact of COVID-19 on mental and physical health is important. Here we replicate and expand a previous study regarding the role of psychological flexibility (PF) in this context. We employed a comprehensive and well validated measure of PF and examined its role in relation to health outcomes and persistent post COVID-19 symptoms. 1174 participants completed standardized measures of depression, anxiety, insomnia and the Multidimensional Psychological Flexibility Inventory (MPFI), and reported the presence of persistent symptoms associated with "long COVID." All PF and psychological inflexibility (PI) facets, except for acceptance, correlated with the three mental health outcomes and with persistent symptoms. PF and PI accounted for significant variance in depression, anxiety, and insomnia after adjusting for background and health status variables. A notable finding was the particularly stronger correlations obtained for the PI facets. Our findings emphasize the potentially mitigating effects of PF on mental ill health, as well as the particularly aggravating effects of PI, in the pandemic context. A novel finding is the significant association of PI with persisting symptoms of COVID.}, } @article {pmid36247098, year = {2022}, author = {Rawlings, GH and Beail, N}, title = {Long-COVID in people with intellectual disabilities: A call for research of a neglected area.}, journal = {British journal of learning disabilities}, volume = {}, number = {}, pages = {}, pmid = {36247098}, issn = {1354-4187}, abstract = {BACKGROUND: Long-COVID (also known as post-coronavirus-19 syndrome) is a term used to describe symptoms that people experience following their recovery from the COVID-19 virus. The severity of long-COVID is well recognised, with healthcare providers commissioning services to diagnose and treat those affected, as well as funded research into the condition.

METHODS: We performed a systematic search for relevant articles but were unable to find any research on long-COVID in people with intellectual disabilities. Due to the lack of data, we have only been able to make extrapolations from what is known about the condition within the general population.

FINDINGS: We provide an overview of long-COVID and its potential relevance to people with an intellectual disability. We have focused specifically on symptoms or signs, prevalence, risk factors and treatments of the condition in this group, highlighting areas for clinical practice and future research from a psychosocial perspective. We raise serious questions about our current understanding and the availability of the evidence-based to inform treatments tailored towards this population.

CONCLUSION: This is the first report that we are aware of on the topic of long-COVID in people with an intellectual disability. The lack of research is preventing us from gaining a greater understanding of how the condition impacts people with an intellectual disability.}, } @article {pmid36247065, year = {2022}, author = {Murugesu, JA}, title = {Vaccines could cut the risk of long covid by two-fifths.}, journal = {New scientist (1971)}, volume = {256}, number = {3407}, pages = {12}, doi = {10.1016/S0262-4079(22)01801-2}, pmid = {36247065}, issn = {0262-4079}, } @article {pmid36245462, year = {2022}, author = {Amin, MA and Khan, II and Nahin, S and Bonna, AS and Afrin, S and Hawlader, MDH}, title = {COVID-19 hospitalization with later long COVID in a person with Down syndrome.}, journal = {Clinical case reports}, volume = {10}, number = {10}, pages = {e6425}, pmid = {36245462}, issn = {2050-0904}, abstract = {Viruses that induce pulmonary difficulties and auto-inflammation are more common in people with Down syndrome. They also have a higher number of comorbidities associated with a worse prognosis than the overall population. Adult patients with acute COVID-19 are increasingly being diagnosed with Long COVID. However, patients with Down syndrome with later long COVID-19 are the first example documented in Bangladesh.}, } @article {pmid36243455, year = {2022}, author = {eBioMedicine, }, title = {First steps towards diagnosing long COVID.}, journal = {EBioMedicine}, volume = {84}, number = {}, pages = {104306}, doi = {10.1016/j.ebiom.2022.104306}, pmid = {36243455}, issn = {2352-3964}, mesh = {*COVID-19/complications/diagnosis ; COVID-19 Testing ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36242969, year = {2022}, author = {Aden, D and Zaheer, S and Kumar, R and Raj, S and Khan, T and Varshney, S}, title = {Beyond COVID-19 and SARS-CoV-2, cardiovascular outcomes of "long covid" from a pathological perspective - a look back and road ahead.}, journal = {Pathology, research and practice}, volume = {239}, number = {}, pages = {154144}, pmid = {36242969}, issn = {1618-0631}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/complications ; Lung ; Post-Acute COVID-19 Syndrome ; }, abstract = {With the decrease in severity of COVID-19 there is a sense of relief in the general population. However, there has been an increased incidence of cardiovascular and other organ complications post-infection, which have raised concerns about long COVID. The term "long COVID" was first used by Perego on social media to denote the persistence of symptoms weeks or months after initial SARS-CoV-2 infection and the term 'long haulers' was first described by Watson and by Yong to identify post-COVID conditions. There has been an increased incidence of sudden cardiac death and MI post-COVID-19 in healthy individuals, sports persons and prominent movie stars. Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 may include 1) Damage to tissues and cells that are important for blood flow, so clotting of blood is increased. 2) Persistence of fragments of virus or its sub-particles/ protein material in a wide range of body sites and, 3) an immune system gone haywire. As the majority of countries across the globe are easing coronavirus precautionary measures, there is an urgent need by health care organizations and policymakers worldwide to generate awareness by educating the public at large, about the ill effects of long-COVID and varied types of post-acute sequelae of COVID-19.}, } @article {pmid36241127, year = {2023}, author = {Kameyama, K and Mizutani, K and Miyake, Y and Iwase, T and Mizutani, Y and Yamada, M and Ito, Y and Ishihara, S and Deguchi, T}, title = {Evaluation of physical and psychological status of health care workers infected with COVID-19 during a hospital outbreak in Japan.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {29}, number = {2}, pages = {126-130}, pmid = {36241127}, issn = {1437-7780}, mesh = {Humans ; Male ; Female ; *COVID-19/epidemiology ; Quality of Life ; SARS-CoV-2 ; Japan/epidemiology ; Health Personnel ; Hospitals ; Disease Outbreaks ; }, abstract = {PURPOSE: COVID-19 causes physical and psychological impacts on health care workers (HCWs), especially when it occurs during an outbreak. As there are few reports on outcomes of HCWs infected with COVID-19 during a hospital outbreak, we investigated the physical and psychological impacts on HCWs infected with COVID-19 during an outbreak in our hospital.

METHODS: During the outbreak in our hospital, 231 people were infected with COVID-19 including patients, HCWs and their families. Among them, 83 HCWs were enrolled in this study. Current quality of life (QOL) was assessed with the EuroQol-visual analogue scales (EQ-VAS), and motivation to keep on working was evaluated by a 10-point analogue scale. Physiological recovery rates including return to work (RTW) period were also analyzed.

RESULTS: One nurse quit work due to anxiety regarding re-infection with COVID-19. The median period to RTW from the diagnosis was 14.0 (12.0-17.0) days. Motivation to keep on working was slightly reduced, and the EQ-VAS was 75.0 (65.0-83.6). There were no significant differences in QOL and motivation between male and female HCWs, nurses and other HCWs, treatment and non-treatment group, and supplemental and non-supplemental oxygen group. The most frequent persistent symptoms at 1,3 and 6 months after infection were anosmia followed by fatigue.

CONCLUSION: Although QOL and motivation to keep on working were slightly reduced, only one HCW quit work. No severe persistent symptoms were observed, and the RTW period was relatively short.}, } @article {pmid36238724, year = {2022}, author = {Williams, ESCP and Martins, TB and Hill, HR and Coiras, M and Shah, KS and Planelles, V and Spivak, AM}, title = {Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.10.03.22280661}, pmid = {36238724}, abstract = {Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of interferon gamma (IFNγ) and interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID. We propose immune exhaustion as the driver of long-COVID, with the complete absence of IFNγ and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.}, } @article {pmid36238713, year = {2022}, author = {Brannock, MD and Chew, RF and Preiss, AJ and Hadley, EC and McMurry, JA and Leese, PJ and Girvin, AT and Crosskey, M and Zhou, AG and Moffitt, RA and Funk, MJ and Pfaff, ER and Haendel, MA and Chute, CG and , }, title = {Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36238713}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {IMPORTANCE: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations.

OBJECTIVE: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C).

EXPOSURES: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination.

MAIN OUTCOMES AND MEASURES: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards.

RESULTS: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).

CONCLUSIONS AND RELEVANCE: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.

KEY POINTS: Question: Does vaccination prior to COVID-19 onset change the risk of long COVID diagnosis?Findings: Four observational analyses of EHRs showed a statistically significant reduction in long COVID risk associated with pre-COVID vaccination (first cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; second cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).Meaning: Vaccination prior to COVID onset has a protective association with long COVID even in the case of breakthrough infections.}, } @article {pmid36238082, year = {2022}, author = {Zhao, Y and Jaber, VR and Lukiw, WJ}, title = {SARS-CoV-2, long COVID, prion disease and neurodegeneration.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {1002770}, pmid = {36238082}, issn = {1662-4548}, support = {R01 AG018031/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; }, } @article {pmid36237184, year = {2022}, author = {Ziegler, CG and Riediger, C and Gruber, M and Kunath, C and Ullrich, M and Pietzsch, J and Nölting, S and Siepmann, T and Bornstein, SR and Remde, H and Constantinescu, G}, title = {Case report: Incidentally discovered case of pheochromocytoma as a cause of long COVID-19 syndrome.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {967995}, pmid = {36237184}, issn = {1664-2392}, mesh = {*Adrenal Gland Neoplasms/complications/diagnosis/surgery ; Adult ; Blood Pressure Monitoring, Ambulatory ; *COVID-19/complications ; Dizziness/complications ; Humans ; *Hypertension/complications ; Male ; Metanephrine ; Normetanephrine ; Phenoxybenzamine ; *Pheochromocytoma/complications/diagnosis/surgery ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pheochromocytomas (PCCs) are rare but potentially lethal tumors that arise from the adrenal medulla. The clinical suspicion and diagnosis of PCC can be challenging due to the non-specific nature of signs and symptoms. In many patients, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could lead to long-term symptoms including fatigue, headaches, and cognitive dysfunction. Here, we present the case of a patient incidentally diagnosed with an adrenal mass that proved to be a PCC after imaging was performed due to persisting complaints after coronavirus disease 2019 (COVID-19) infection. A 37-year-old male patient was referred to our center because of a right-sided inhomogeneous adrenal mass, incidentally found during a computed tomographic scan of the thorax performed due to cough and dyspnea that persisted after COVID-19 infection. Other complaints that were present prior to COVID-19 infection included profuse sweating, dizziness, exhaustion with chronic fatigue, and concentration difficulties. The patient had no history of hypertension, his blood pressure was normal, and the 24-h ambulatory blood pressure monitoring confirmed normotension but with the absence of nocturnal dipping. Plasma normetanephrine was 5.7-fold above the upper limit (UL) of reference intervals (738 pg/ml, UL = 129 pg/ml), whereas plasma metanephrine and methoxytyramine were normal at 30 pg/ml (UL = 84 pg/ml) and <4 pg/ml (UL = 16 pg/ml), respectively. Preoperative preparation with phenoxybenzamine was initiated, and a 4-cm tumor was surgically resected. Profuse sweating as well as dizziness was resolved after adrenalectomy pointing toward PCC and not COVID-19-associated patient concerns. Altogether, this case illustrates the difficulties in recognizing the possibility of PCC due to the non-specific nature of signs and symptoms of the tumor, which in this case did not include hypertension and coincided with some of the symptoms of long COVID-19.}, } @article {pmid36233830, year = {2022}, author = {Rinaldi, R and Basile, M and Salzillo, C and Grieco, DL and Caffè, A and Masciocchi, C and Lilli, L and Damiani, A and La Vecchia, G and Iannaccone, G and Bonanni, A and De Pascale, G and Murri, R and Fantoni, M and Liuzzo, G and Sanna, T and Massetti, M and Gasbarrini, A and Valentini, V and Antonelli, M and Crea, F and Montone, RA and On Behalf Of The Gemelli Against Covid Group, }, title = {Myocardial Injury Portends a Higher Risk of Mortality and Long-Term Cardiovascular Sequelae after Hospital Discharge in COVID-19 Survivors.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233830}, issn = {2077-0383}, support = {Ricerca Corrente di Rete 2021-23671212//Italian Ministry of Health/ ; Program PON "Research and Innovation"//Italian Ministry for University and Research/ ; }, abstract = {Background: Cardiovascular sequelae after COVID-19 are frequent. However, the predictors for their occurrence are still unknown. In this study, we aimed to assess whether myocardial injury during COVID-19 hospitalization is associated to CV sequelae and death after hospital discharge. Methods: In this prospective observational study, consecutive patients who were admitted for COVID-19 in a metropolitan COVID-19 hub in Italy, between March 2021 and January 2022, with a ≥ 1 assessment of high sensitivity cardiac troponin I (hs-cTnI) were included in the study, if they were alive at hospital discharge. Myocardial injury was defined as elevation hs-cTnI > 99th percentile of the upper reference limit. The incidence of all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, admission for acute or chronic coronary syndrome, hospitalization for heart failure, and stroke/transient ischemic attack) at follow-up were the primary outcomes. Arrhythmias, inflammatory heart diseases, and/or thrombotic disorders were analyzed as well. Results: Among the 701 COVID-19 survivors (mean age 66.4 ± 14.4 years, 40.2% female), myocardial injury occurred in 75 (10.7%) patients. At a median follow-up of 270 days (IQR 165, 380), all-cause mortality (21.3% vs. 6.1%, p < 0.001), MACCE (25.3% vs. 4.5%, p < 0.001), arrhythmias (9.3% vs. 5.0%, p = 0.034), and inflammatory heart disease (8.0% vs. 1.1%, p < 0.001) were more frequent in patients with myocardial injury compared to those without. At multivariate analysis, myocardial injury (HR 1.95 [95% CI:1.05−3.61]), age (HR 1.09 [95% CI:1.06−1.12]), and chronic kidney disease (HR 2.63 [95% CI:1.33−5.21]) were independent predictors of death. Myocardial injury (HR 3.92 [95% CI:2.07−7.42]), age (HR 1.05 [95% CI:1.02−1.08]), and diabetes (HR 2.35 [95% CI:1.25−4.43]) were independent predictors of MACCE. Conclusion: In COVID-19 survivors, myocardial injury during the hospital stay portends a higher risk of mortality and cardiovascular sequelae and could be considered for the risk stratification of COVID-19 sequelae in patients who are successfully discharged.}, } @article {pmid36233769, year = {2022}, author = {Rodríguez-Pérez, MP and Sánchez-Herrera-Baeza, P and Rodríguez-Ledo, P and Serrada-Tejeda, S and García-Bravo, C and Pérez-de-Heredia-Torres, M}, title = {Headaches and Dizziness as Disabling, Persistent Symptoms in Patients with Long COVID-A National Multicentre Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233769}, issn = {2077-0383}, abstract = {Background: Currently, about 15% of coronavirus disease-19 (COVID-19) patients are affected by Long COVID worldwide; however, this condition has not yet been sufficiently studied. The aim of this study was to identify the impact of symptom persistence as well as clinical and socio-demographic variables in a cohort of people with Long COVID. Methods: We conducted a descriptive cross-sectional study of a sample of adult patients from different Spanish regions presenting with Long COVID. Data collection was conducted between April and July 2021. Functional status and dependency were assessed. Results: A multivariate linear regression was performed, and the model was statistically significant (F (7; 114) = 8.79; p < 0.001), according to the overall ALDQ score. The variables with a statistically significant effect on the degree of dependence were age (p = 0.014), time since diagnosis (p = 0.02), headaches (p = 0.031), and dizziness (p = 0.039). Functional status post-COVID showed a positive and significant relationship with the percentage of dependence (p < 0.001). Conclusions: People affected by Long COVID showed moderate dependency status and limitations in functionality. Those with neurological symptoms, such as dizziness and headaches, as well as older age, showed a higher degree of dependency. Improvements in dependency status occurred with increasing time since diagnosis.}, } @article {pmid36233559, year = {2022}, author = {Clerbaux, LA and Mayasich, SA and Muñoz, A and Soares, H and Petrillo, M and Albertini, MC and Lanthier, N and Grenga, L and Amorim, MJ}, title = {Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233559}, issn = {2077-0383}, support = {CEECIND/02373/2020//Fundação para a Ciência e Tecnologia/ ; CEECIND/01049/2020//Fundação para a Ciência e Tecnologia/ ; }, abstract = {The gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract, the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the detection of SARS-CoV-2 RNA in feces. However, the underlying mechanisms remain poorly understood. It has been proposed that SARS-CoV-2 can productively infect enterocytes, damaging the intestinal barrier and contributing to inflammatory response, which might lead to GI manifestations, including diarrhea. Here, we report a methodological approach to assess the evidence supporting the sequence of events driving SARS-CoV-2 enteric infection up to gut adverse outcomes. Exploring evidence permits to highlight knowledge gaps and current inconsistencies in the literature and to guide further research. Based on the current insights on SARS-CoV-2 intestinal infection and transmission, we then discuss the potential implication on clinical practice, including on long COVID. A better understanding of the GI implication in COVID-19 is still needed to improve disease management and could help identify innovative therapies or preventive actions targeting the GI tract.}, } @article {pmid36233555, year = {2022}, author = {Katzenstein, TL and Christensen, J and Lund, TK and Kalhauge, A and Rönsholt, F and Podlekareva, D and Arndal, E and Berg, RMG and Helt, TW and Lebech, AM and Mortensen, J}, title = {Relation of Pulmonary Diffusing Capacity Decline to HRCT and VQ SPECT/CT Findings at Early Follow-Up after COVID-19: A Prospective Cohort Study (The SECURe Study).}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233555}, issn = {2077-0383}, abstract = {A large proportion of patients exhibit persistently reduced pulmonary diffusion capacity after COVID-19. It is unknown whether this is due to a post-COVID restrictive lung disease and/or pulmonary vascular disease. The aim of the current study was to investigate the association between initial COVID-19 severity and haemoglobin-corrected diffusion capacity to carbon monoxide (DLco) reduction at follow-up. Furthermore, to analyse if DLco reduction could be linked to pulmonary fibrosis (PF) and/or thromboembolic disease within the first months after the illness, a total of 67 patients diagnosed with COVID-19 from March to December 2020 were included across three severity groups: 12 not admitted to hospital (Group I), 40 admitted to hospital without intensive care unit (ICU) admission (Group II), and 15 admitted to hospital with ICU admission (Group III). At first follow-up, 5 months post SARS-CoV-2 positive testing/4 months after discharge, lung function testing, including DLco, high-resolution CT chest scan (HRCT) and ventilation-perfusion (VQ) single photon emission computed tomography (SPECT)/CT were conducted. DLco was reduced in 42% of the patients; the prevalence and extent depended on the clinical severity group and was typically observed as part of a restrictive pattern with reduced total lung capacity. Reduced DLco was associated with the extent of ground-glass opacification and signs of PF on HRCT, but not with mismatched perfusion defects on VQ SPECT/CT. The severity-dependent decline in DLco observed early after COVID-19 appears to be caused by restrictive and not pulmonary vascular disease.}, } @article {pmid36233516, year = {2022}, author = {Fernández-de-Las-Peñas, C and Giordano, R and Díaz-Gil, G and Gómez-Esquer, F and Ambite-Quesada, S and Palomar-Gallego, MA and Arendt-Nielsen, L}, title = {Post-COVID Pain Is Not Associated with Inflammatory Polymorphisms in People Who Had Been Hospitalized by COVID-19.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233516}, issn = {2077-0383}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; NNF21OC0067235//Novo Nordisk Foundation/ ; }, abstract = {Our aim was to assess the association between four inflammatory polymorphisms with the development of post-COVID pain and to associate these polymorphisms with the clinical pain phenotype in individuals who had been hospitalized by COVID-19. Three potential genotypes of IL-6 (rs1800796), IL-10 (rs1800896), TNF-α (rs1800629), and IFITM3 (rs12252) single nucleotide polymorphisms (SNPs) were obtained from no-stimulated saliva samples from 293 (49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors by polymerase chain reactions. Pain phenotyping consisted of the evaluation of pain features, sensitization-associated symptoms, anxiety levels, depressive levels, sleep quality, catastrophizing, and kinesiophobia levels in patients with post-COVID pain. Analyses were conducted to associate clinical features with genotypes. One hundred and seventeen (39.9%) patients experienced post-COVID pain 17.8 ± 5.2 months after hospital discharge. No significant differences in the distribution of the genotype variants of any SNPs were identified between COVID-19 survivors with and without post-COVID pain (all, p > 0.47). Similarly, the clinical pain phenotype was not significantly different between patients with and without post-COVID pain since no differences in any variable were observed for any SNPs. In conclusion, four SNPs associated with inflammatory and immune responses did not appear to be associated with post-COVID pain in previously hospitalized COVID-19 survivors. Further, neither of the SNPs were involved in the phenotyping features of post-COVID pain.}, } @article {pmid36233447, year = {2022}, author = {Okoye, C and Calsolaro, V and Calabrese, AM and Zotti, S and Fedecostante, M and Volpato, S and Fumagalli, S and Cherubini, A and Antonelli Incalzi, R and Monzani, F and , }, title = {Determinants of Cause-Specific Mortality and Loss of Independence in Older Patients following Hospitalization for COVID-19: The GeroCovid Outcomes Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233447}, issn = {2077-0383}, abstract = {Hospitalization for acute SARS-CoV-2 infection confers an almost five-fold higher risk of post-discharge, all-cause mortality compared to controls from the general population. A negative impact on the functional autonomy of older patients, especially in cases of severe disease and prolonged hospitalization, has been recently described. However, little is known about the determinants of cause-specific mortality and loss of independence (LOI) in the activities of daily living (ADL) following COVID-19 hospitalization. Thus, the current prospective, multicenter study is aimed at identifying the determinants of post-discharge cause-specific mortality and the loss of autonomy in at least one ADL function. Older patients hospitalized for a SARS-CoV-2 infection were consecutively enrolled in an e-Registry from 1 March 2020, until 31 December 2020. After at least six months from discharge, patients were extensively re-evaluated according to a common protocol at the outpatient clinic of eight tertiary care Italian hospitals. Of 193 patients [109 (56.4%) men, mean age 79.9 ± 9.1 years], 43 (22.3%) died during follow-up. The most common causes of death were cardiovascular diseases (46.0%), respiratory failure (26.5%), and gastrointestinal and genitourinary diseases (8.8% each). Pre-morbid ADLs qualified as an independent mortality risk factor [adjusted HR 0.77 (95%CI: 0.63-0.95)]. Of 132 patients, 28 (21.2%) lost their independence in at least one ADL. The adjusted risk of LOI declined with a lower frailty degree [aOR 0.03 (95%CI: 0.01-0.32)]. In conclusion, at long-term follow-up after hospitalization for acute SARS-CoV-2 infection, more than 40% of older patients died or experienced a loss of functional independence compared to their pre-morbid condition. Given its high prevalence, the loss of functional independence after hospitalization for COVID-19 could be reasonably included among the features of the "Long COVID-19 syndrome" of older patients.}, } @article {pmid36233443, year = {2022}, author = {Zis, P and Ioannou, C and Artemiadis, A and Christodoulou, K and Kalampokini, S and Hadjigeorgiou, GM}, title = {Prevalence and Determinants of Chronic Pain Post-COVID; Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233443}, issn = {2077-0383}, abstract = {INTRODUCTION: Chronic pain is increasingly recognized as part of long COVID syndrome, mainly in the form of myalgias. However, chronic pain has several forms, and according to our clinical experience, COVID-19 survivors suffer from numerous painful syndromes, other than myalgias. The aim of our study was to estimate the prevalence of chronic pain, describe the commonest painful syndromes and identify pain determinants in a random population of COVID-19 survivors.

METHODS: This was a cross-sectional study conducted at the Medical School, University of Cyprus. A random population of 90 COVID-19 survivors was recruited. Demographic and COVID-19 related clinical characteristics were recorded. The painDETECT and DN4 questionnaires were used to evaluate the painful syndromes.

RESULTS: The prevalence of chronic pain was estimated to be 63.3%. The most common site of pain was low back (37.8%), followed by joints (28.9%) and neck (12.2%). Patients with chronic pain compared to subjects without pain were older (50.5 ± 15.9 versus 42.2 ± 12.6, p = 0.011) and more likely to be female (71.9% versus 45.5%, p = 0.013). One in six subjects (16.7%) reported new-onset pain post COVID-19. The prevalence of neuropathic pain was estimated to be 24.4%. After adjusting for age and gender, headache during COVID-19 was a statistically significant predictor of neuropathic pain, increasing 4.9 times (95% 1.4-16.6, p = 0.011) the odds of neuropathic pain.

CONCLUSION: Chronic pain-especially neuropathic-is widely prevalent in COVID-19 survivors. One in six subjects will develop new-onset pain that will persist beyond the acute phase of the disease and, therefore, should be considered a symptom of long COVID syndrome.}, } @article {pmid36233392, year = {2022}, author = {Orfei, MD and Porcari, DE and D'Arcangelo, S and Maggi, F and Russignaga, D and Ricciardi, E}, title = {A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome.}, journal = {Journal of clinical medicine}, volume = {11}, number = {19}, pages = {}, pmid = {36233392}, issn = {2077-0383}, support = {289/2021//Intesa Sanpaolo Innovation Center; Programmazione Triennale (PRO3) project: 'Neurocognitive, sensory-motor, and emotional out-comes following the pandemic in populations at risk'/ ; }, abstract = {Epidemiological data and etiopathogenesis of brain fog are very heterogeneous in the literature, preventing adequate diagnosis and treatment. Our study aimed to explore the relationship between brain fog, neuropsychiatric and cognitive symptoms in the general population. A sample of 441 subjects underwent a web-based survey, including the PANAS, the DASS-21, the IES-R, the Beck Cognitive Insight Scale, and a questionnaire investigating demographic information, brain fog, subjective cognitive impairments (Scc) and sleep disorders. ANOVA, ANCOVA, correlation and multiple stepwise regression analyses were performed. In our sample, 33% of participants were defined as Healthy Subjects (HS; no brain fog, no Scc), 27% as Probable Brain Fog (PBF; brain fog or Scc), and 40% as Functional Brain Fog (FBF; brain fog plus Scc). PBF and FBF showed higher levels of neuropsychiatric symptoms than HS, and FBF showed the worst psychological outcome. Moreover, worse cognitive symptoms were related to the female gender, greater neuropsychiatric symptoms, sleep disorders, and rumination/indecision. Being a woman and more severe neuropsychiatric symptoms were predictors of FBF severity. Our data pointed out a high prevalence and various levels of severity and impairments of brain fog, suggesting a classificatory proposal and a multifaceted etiopathogenic model, thus facilitating adequate diagnostic and therapeutic approaches.}, } @article {pmid36233149, year = {2022}, author = {MacRaild, CA and Mohammed, MU and Faheem, and Murugesan, S and Styles, IK and Peterson, AL and Kirkpatrick, CMJ and Cooper, MA and Palombo, EA and Simpson, MM and Jain, HA and Agarwal, V and McAuley, AJ and Kumar, A and Creek, DJ and Trevaskis, NL and Vasan, SS}, title = {Systematic Down-Selection of Repurposed Drug Candidates for COVID-19.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36233149}, issn = {1422-0067}, support = {75F40121C00144//United States Food and Drug Administration/ ; MRF2009092//National Health and Medical Research Council/ ; }, mesh = {Antiviral Agents/pharmacology/therapeutic use ; *COVID-19/complications ; Drug Repositioning ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {SARS-CoV-2 is the cause of the COVID-19 pandemic which has claimed more than 6.5 million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as the current vaccines cannot prevent all infections. This situation calls for the collaboration of biomedical scientists and healthcare workers across the world. Repurposing approved drugs is an effective way of fast-tracking new treatments for recently emerged diseases. To this end, we have assembled and curated a database consisting of 7817 compounds from the Compounds Australia Open Drug collection. We developed a set of eight filters based on indicators of efficacy and safety that were applied sequentially to down-select drugs that showed promise for drug repurposing efforts against SARS-CoV-2. Considerable effort was made to evaluate approximately 14,000 assay data points for SARS-CoV-2 FDA/TGA-approved drugs and provide an average activity score for 3539 compounds. The filtering process identified 12 FDA-approved molecules with established safety profiles that have plausible mechanisms for treating COVID-19 disease. The methodology developed in our study provides a template for prioritising drug candidates that can be repurposed for the safe, efficacious, and cost-effective treatment of COVID-19, long COVID, or any other future disease. We present our database in an easy-to-use interactive interface (CoviRx that was also developed to enable the scientific community to access to the data of over 7000 potential drugs and to implement alternative prioritisation and down-selection strategies.}, } @article {pmid36232592, year = {2022}, author = {Khodanovich, MY and Kamaeva, DA and Naumova, AV}, title = {Role of Demyelination in the Persistence of Neurological and Mental Impairments after COVID-19.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232592}, issn = {1422-0067}, support = {22-15-00481//Russian Science Foundation/ ; }, mesh = {*Attention Deficit Disorder with Hyperactivity ; *COVID-19/complications ; *Demyelinating Diseases/complications ; Humans ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term neurological and mental complications of COVID-19, the so-called post-COVID syndrome or long COVID, affect the quality of life. The most persistent manifestations of long COVID include fatigue, anosmia/hyposmia, insomnia, depression/anxiety, and memory/attention deficits. The physiological basis of neurological and psychiatric disorders is still poorly understood. This review summarizes the current knowledge of neurological sequelae in post-COVID patients and discusses brain demyelination as a possible mechanism of these complications with a focus on neuroimaging findings. Numerous reviews, experimental and theoretical studies consider brain demyelination as one of the mechanisms of the central neural system impairment. Several factors might cause demyelination, such as inflammation, direct effect of the virus on oligodendrocytes, and cerebrovascular disorders, inducing myelin damage. There is a contradiction between the solid fundamental basis underlying demyelination as the mechanism of the neurological injuries and relatively little published clinical evidence related to demyelination in COVID-19 patients. The reason for this probably lies in the fact that most clinical studies used conventional MRI techniques, which can detect only large, clearly visible demyelinating lesions. A very limited number of studies use specific methods for myelin quantification detected changes in the white matter tracts 3 and 10 months after the acute phase of COVID-19. Future research applying quantitative MRI assessment of myelin in combination with neurological and psychological studies will help in understanding the mechanisms of post-COVID complications associated with demyelination.}, } @article {pmid36232113, year = {2022}, author = {Chatys-Bogacka, Z and Mazurkiewicz, I and Slowik, J and Bociaga-Jasik, M and Dzieza-Grudnik, A and Slowik, A and Wnuk, M and Drabik, L}, title = {Brain Fog and Quality of Life at Work in Non-Hospitalized Patients after COVID-19.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {19}, pages = {}, pmid = {36232113}, issn = {1660-4601}, mesh = {Adult ; Brain ; *COVID-19/epidemiology ; Female ; Humans ; Male ; Quality of Life ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {Background: There is still a need for studies on the quality of life (QoL) at work among COVID-19 survivors. Therefore, we aimed to evaluate the association between the brain fog symptoms and the QoL at work in non-hospitalized patients with previous SARS-CoV-2 infection. Methods: Three hundred non-hospitalized patients (79.33% women; median age, 36 years; interquartile range, 30-48 years) were included in the final analysis. An anonymous neuropsychological questionnaire containing eight different questions on the presence of brain fog symptoms in four time intervals, i.e., pre-COVID-19 and 0-4, 4-12, and >12 weeks after infection, was retrospectively introduced to patients and staff of the University Hospital in Krakow. Additionally, a four-point Likert scale was used to evaluate QoL at work in four time periods. Included were participants aged ≥ 18 years in whom the diagnosis of COVID-19 was confirmed by the RT-PCR from nasopharyngeal swab and the first symptoms occurred no earlier than 3 months before the completion of the questionnaire. Results: Before SARS-CoV-2 infection, 28.00% (n = 84) of patients reported poor QoL at work. Within 4, 4-12, and >12 weeks after infection, a decrease in QoL was observed in 75.67% (n = 227), 65.00% (n = 195), and 53.66% (n = 161) of patients, respectively (p < 0.001). With increasing deterioration of the QoL at work, the number of brain fog symptoms increased, and patients with severe QoL impairment exhibited a median of five symptoms for <4, 4-12, and >12 weeks post-COVID-19. In the multivariable logistic regression model, predictors of the deterioration of the QoL at work depended on the time from COVID-19 onset; in the acute phase of the disease (<4 weeks), it was predicted by impairment in remembering information from the past (OR 1.88, 95%CI: 1.18-3.00, p = 0.008) and multitasking (OR 1.96, 95%CI: 1.48-2.58, p < 0.001). Furthermore, an impairment in the QoL at work 4-12 weeks and >12 weeks after COVID-19 was independently associated with age (OR 0.46, 95%CI: 0.25-0.85, p = 0.014 and OR 1.03, 95%CI: 1.01-1.05, p = 0.025, respectively), problems with multitasking (OR 2.05, 95%CI: 1.40-3.01, p < 0.001 and OR 1.75, 95%CI: 1.15-2.66, p = 0.009, respectively), answering questions in an understandable/unambiguous manner (OR 1.99, 95%CI: 1.27-3.14, p = 0.003 and OR 2.00, 95%CI: 1.47-2.36, p = 0.001, respectively), and, only for the >12 week interval, problems with remembering information from the past (OR 2.21, 95%CI: 1.24-3.92, p = 0.007). Conclusions: Certain brain fog symptoms, such as impaired memory or multitasking, are predictors of a poorer QoL at work not only during the acute phase of COVID-19 but also within more than 12 weeks after the onset of infection.}, } @article {pmid36231979, year = {2022}, author = {Flannery, T and Brady-Sawant, H and Tarrant, R and Davison, J and Shardha, J and Halpin, S and Sivan, M and Ross, D}, title = {A Mixed-Methods Evaluation of a Virtual Rehabilitation Program for Self-Management in Post-COVID-19 Syndrome (Long COVID).}, journal = {International journal of environmental research and public health}, volume = {19}, number = {19}, pages = {}, pmid = {36231979}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Health Personnel/education ; Humans ; *Self-Management ; *Telerehabilitation ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID (LC) symptoms can be long standing, diverse and debilitating; comprehensive multidisciplinary rehabilitation programs are required to address this. A 10-week LC Virtual Rehabilitation Program (VRP) was developed to provide early education and self-management techniques to address the main symptoms of LC and was delivered to a group of persons with Long COVID (PwLC) online, facilitated by members of the multi-disciplinary rehabilitation team. This paper describes an evaluation of this VRP. Questionnaires completed by Healthcare Professionals (HCP) delivering the VRP were thematically analyzed to gain a priori themes and design semi-structured telephone interview questions for PwLC. Template analysis (TA) was used to analyze interview data. Routinely collected patient demographics and service data were also examined. Seventeen HCP survey responses were obtained and 38 PwLC telephone questionnaires were completed. The HCP interviews generated three a priori themes (1. Attendance and Availability, 2. Content, 3. Use of Digital Technology). TA was applied and three further themes emerged from the combined HCP and PwLC responses (4. Group Dynamics, 5. Individual Factors, 6. Internal Change). Key outcomes demonstrated that: the VRP was highly valued; digital delivery enabled self-management; barriers to attendance included work/life balance, use of technology, health inequalities; and LC was poorly understood by employers. Recommendations are provided for the design of VRPs for LC.}, } @article {pmid36231893, year = {2022}, author = {Ramos-Usuga, D and Perrin, PB and Bogdanova, Y and Olabarrieta-Landa, L and Alzueta, E and Baker, FC and Iacovides, S and Cortes, M and Arango-Lasprilla, JC}, title = {Moderate, Little, or No Improvements in Neurobehavioral Symptoms among Individuals with Long COVID: A 34-Country Retrospective Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {19}, pages = {}, pmid = {36231893}, issn = {1660-4601}, mesh = {Adult ; *COVID-19/complications/epidemiology ; COVID-19 Testing ; Female ; Humans ; Infant, Newborn ; Male ; Oxygen ; Quality of Life ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {(1) Background: Some people with COVID-19 develop a series of symptoms that last for several months after infection, known as Long COVID. Although these symptoms interfere with people's daily functioning and quality of life, few studies have focused on neurobehavioral symptoms and the risk factors associated with their development; (2) Methods: 1001 adults from 34 countries who had previously tested positive for COVID-19 completed the Neurobehavioral Symptom Inventory reporting the symptoms before their COVID-19 diagnosis, during the COVID-19 infection, and currently; (3) Results: Participants reported large-sized increases before vs. during COVID-19 in all domains. Participants reported a medium-sized improvement (during COVID-19 vs. now) in somatic symptoms, a small-sized improvement in affective symptoms, and very minor/no improvement in cognitive symptoms. The risk factors for increased neurobehavioral symptoms were: being female/trans, unemployed, younger age, low education, having another chronic health condition, greater COVID-19 severity, greater number of days since the COVID-19 diagnosis, not having received oxygen therapy, and having been hospitalized. Additionally, participants from North America, Europe, and Central Asia reported higher levels of symptoms across all domains relative to Latin America and Sub-Saharan Africa; (4) Conclusions: The results highlight the importance of evaluating and treating neurobehavioral symptoms after COVID-19, especially targeting the higher-risk groups identified. General rehabilitation strategies and evidence-based cognitive rehabilitation are needed in both the acute and Long COVID phases.}, } @article {pmid36231717, year = {2022}, author = {Gao, P and Liu, J and Liu, M}, title = {Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {19}, pages = {}, pmid = {36231717}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology/prevention & control ; *COVID-19 Vaccines/therapeutic use ; Humans ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) is still in a global pandemic state. Some studies have reported that COVID-19 vaccines had a protective effect against long COVID. However, the conclusions of the studies on the effect of COVID-19 vaccines on long COVID were not consistent. This study aimed to systematically review relevant studies in the real world, and performed a meta-analysis to explore the relationship between vaccination and long COVID. We systematically searched PubMed, Embase, Web of science, and ScienceDirect from inception to 19 September 2022. The PICO (P: patients; I: intervention; C: comparison; O: outcome) was as follows: patients diagnosed with COVID-19 (P); vaccination with COVID-19 vaccines (I); the patients were divided into vaccinated and unvaccinated groups (C); the outcomes were the occurrence of long COVID, as well as the various symptoms of long COVID (O). A fixed-effect model and random-effects model were chosen based on the heterogeneity between studies in order to pool the effect value. The results showed that the vaccinated group had a 29% lower risk of developing long COVID compared with the unvaccinated group (RR = 0.71, 95% CI: 0.58-0.87, p < 0.01). Compared with patients who were not vaccinated, vaccination showed its protective effect in patients vaccinated with two doses (RR = 0.83, 95% CI: 0.74-0.94, p < 0.01), but not one dose (RR = 0.83, 95% CI: 0.65-1.07, p = 0.14). In addition, vaccination was effective against long COVD in patients either vaccinated before SARS-CoV-2 infection/COVID-19 (RR = 0.82, 95% CI: 0.74-0.91, p < 0.01) or vaccinated after SARS-CoV-2 infection/COVID-19 (RR = 0.83, 95% CI: 0.74-0.92, p < 0.01). For long COVID symptoms, vaccination reduced the risk of cognitive dysfunction/symptoms, kidney diseases/problems, myalgia, and sleeping disorders/problems sleeping. Our study shows that COVID-19 vaccines had an effect on reducing the risk of long COVID in patients vaccinated before or after SARS-CoV-2 infection/COVID-19. We suggest that the vaccination rate should be improved as soon as possible, especially for a complete vaccination course. There should be more studies to explore the basic mechanisms of the protective effect of COVID-19 vaccines on long COVID in the future.}, } @article {pmid36228563, year = {2022}, author = {Rizvi, AA and Kathuria, A and Al Mahmeed, W and Al-Rasadi, K and Al-Alawi, K and Banach, M and Banerjee, Y and Ceriello, A and Cesur, M and Cosentino, F and Galia, M and Goh, SY and Janez, A and Kalra, S and Kempler, P and Lessan, N and Lotufo, P and Papanas, N and Santos, RD and Stoian, AP and Toth, PP and Viswanathan, V and Rizzo, M and , }, title = {Post-COVID syndrome, inflammation, and diabetes.}, journal = {Journal of diabetes and its complications}, volume = {36}, number = {11}, pages = {108336}, pmid = {36228563}, issn = {1873-460X}, mesh = {Humans ; SARS-CoV-2 ; Pandemics ; *COVID-19/complications ; RNA, Viral ; *Diabetes Mellitus/epidemiology/therapy ; *Hyperglycemia/complications ; Inflammation/complications ; }, abstract = {The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.}, } @article {pmid36228200, year = {2022}, author = {Amorim, CEN and Gomes, VLT and Cristelli, MP and Viana, LA and de Luca Correa, H and Lima, GBB and de Sousa Silva, FS and de Castro Lima, GS and Rosa, TDS and Nakamura, MR and Quintino, PM and Tedesco-Silva, H and Medina-Pestana, J}, title = {High Prevalence of Long-COVID Among Kidney Transplant Recipients: A Longitudinal Cohort Study.}, journal = {Transplantation}, volume = {106}, number = {12}, pages = {2408-2415}, pmid = {36228200}, issn = {1534-6080}, mesh = {Adult ; Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology ; *Kidney Transplantation/adverse effects ; Longitudinal Studies ; Prospective Studies ; Prevalence ; Acute Disease ; Transplant Recipients ; Cohort Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Kidney transplant recipients are at a higher risk to develop more severe clinical forms of coronavirus disease 2019 (COVID-19), perhaps increasing the risk of presenting its long-term clinical complications, labeled as Long-COVID.

METHODS: This single-center, observational, prospective study included adult kidney transplant recipients with COVID-19 confirmed by reverse transcription polymerase chain reaction between March 20, 2020, and May 31, 2021, who were alive and with functioning graft 3 mo after the onset of symptoms. The prevalence of Long-COVID was investigated by a phone survey using a structured questionnaire of organic symptoms. Adjusted multivariable logistic regression models were used to investigate independent risk factors.

RESULTS: Of 1741 patients who developed COVID-19, 465 died, and 37 returned to dialysis. Of the 1239 eligible patients, 780 (63%) answered the survey during the window period. The mean age was 48 ± 12 y, 41% were women, and the mean time from transplantation was 8 ± 6 y. During acute illness, 45% needed hospitalization. Long-COVID was identified in 214 (27%) of the subjects, with body aches being the most prevalent symptom (44%). Of 233 who provided working status, 17% did not return to work within 3 mo. No baseline characteristics or infection-related variables predicted Long-COVID; actually, the number of symptoms in the acute illness was the only independent risk factor identified (hazard ratio, 1.12; 95% confidence interval, 1.02-1.22).

CONCLUSION: In this cohort of kidney transplant recipients, Long-COVID was prevalent and associated with a reduced return to work. The burden of acute phase symptoms was the only risk factor associated with Long-COVID.}, } @article {pmid36227557, year = {2023}, author = {Duan, E and Garry, K and Horwitz, LI and Weerahandi, H}, title = {"I Am Not the Same as I Was Before": A Qualitative Analysis of COVID-19 Survivors.}, journal = {International journal of behavioral medicine}, volume = {30}, number = {5}, pages = {663-672}, pmid = {36227557}, issn = {1532-7558}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; OTA2HL161847/HL/NHLBI NIH HHS/United States ; K23HL145110/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Cohort Studies ; Quality of Life/psychology ; Survivors ; }, abstract = {BACKGROUND: Little is known about the illness experience of patients' long-term emotional and physical recovery from severe COVID-19 infection. This study aimed to expand upon the recovery process of COVID-19 survivors up to 6 months after hospital discharge.

METHODS: Qualitative analysis of free-response answers from a cohort study of 152 patients ≥ 18 years hospitalized with laboratory-confirmed SARS-CoV-2 surveyed at 1-month post hospital discharge and 6-months post hospital discharge. Responses were analyzed with a grounded theory approach to identify overarching themes.

RESULTS: Participants described persistent complications, both physical and mental, that have affected their recovery from COVID-19. Five overarching themes of post-acute patient experiences were generated: (1) an increased awareness of a mind and body connection, (2) feelings of premature aging, (3) an overall decline in quality of life, (4) a continued fear of infection, and (5) methods of coping.

CONCLUSIONS: Patients described lasting changes to their mental health and overall quality of life in connection to physical complications after severe COVID-19 infection. Patients' reports of their experience call for a greater awareness of the psychological aspects of COVID-19 recovery to provide both physical and psychological rehabilitation services. Additional resources such as education around re-infection and financial resources are needed.}, } @article {pmid36227021, year = {2023}, author = {Yang, DM and Chang, TJ and Hung, KF and Wang, ML and Cheng, YF and Chiang, SH and Chen, MF and Liao, YT and Lai, WQ and Liang, KH}, title = {Smart healthcare: A prospective future medical approach for COVID-19.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {86}, number = {2}, pages = {138-146}, pmid = {36227021}, issn = {1728-7731}, mesh = {Humans ; *COVID-19 ; Artificial Intelligence ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Delivery of Health Care ; }, abstract = {COVID-19 has greatly affected human life for over 3 years. In this review, we focus on smart healthcare solutions that address major requirements for coping with the COVID-19 pandemic, including (1) the continuous monitoring of severe acute respiratory syndrome coronavirus 2, (2) patient stratification with distinct short-term outcomes (eg, mild or severe diseases) and long-term outcomes (eg, long COVID), and (3) adherence to medication and treatments for patients with COVID-19. Smart healthcare often utilizes medical artificial intelligence (AI) and cloud computing and integrates cutting-edge biological and optoelectronic techniques. These are valuable technologies for addressing the unmet needs in the management of COVID. By leveraging deep learning/machine learning capabilities and big data, medical AI can perform precise prognosis predictions and provide reliable suggestions for physicians' decision-making. Through the assistance of the Internet of Medical Things, which encompasses wearable devices, smartphone apps, internet-based drug delivery systems, and telemedicine technologies, the status of mild cases can be continuously monitored and medications provided at home without the need for hospital care. In cases that develop into severe cases, emergency feedback can be provided through the hospital for rapid treatment. Smart healthcare can possibly prevent the development of severe COVID-19 cases and therefore lower the burden on intensive care units.}, } @article {pmid36226564, year = {2022}, author = {Jette, AM}, title = {The Looming Challenge of Long COVID.}, journal = {Physical therapy}, volume = {102}, number = {11}, pages = {}, doi = {10.1093/ptj/pzac147}, pmid = {36226564}, issn = {1538-6724}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Photic Stimulation ; }, } @article {pmid36226380, year = {2023}, author = {Pisareva, E and Badiou, S and Mihalovičová, L and Mirandola, A and Pastor, B and Kudriavtsev, A and Berger, M and Roubille, C and Fesler, P and Klouche, K and Cristol, JP and Thierry, AR}, title = {Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28209}, pmid = {36226380}, issn = {1096-9071}, mesh = {Humans ; *Extracellular Traps ; Prospective Studies ; Antibodies, Anticardiolipin ; *COVID-19/pathology ; Immunoglobulin G ; Immunoglobulin M ; Neutrophils ; }, abstract = {In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.}, } @article {pmid36226231, year = {2022}, author = {Alkwai, HM and Khalifa, AM and Ahmed, AM and Alnajib, AM and Alshammari, KA and Alrashidi, MM and Ahmed, HG}, title = {Persistence of COVID-19 symptoms beyond 3 months and the delayed return to the usual state of health in Saudi Arabia: A cross-sectional study.}, journal = {SAGE open medicine}, volume = {10}, number = {}, pages = {20503121221129918}, pmid = {36226231}, issn = {2050-3121}, abstract = {UNLABELLED: A substantial number of COVID-19 survivors describe ongoing symptoms long after the acute phase. This so-called post-COVID-19 syndrome or long COVID occurs irrespective of initial disease severity.

OBJECTIVES: This cross-sectional study aims to describe and characterise the prevalence of persistent COVID-19 symptoms beyond three months and to evaluate the risk factors for the delayed return to the usual state of health.

METHODS: An electronic survey was developed, piloted, and conducted during the first wave of the COVID-19 pandemic. The survey consisted of questions exploring socio-demographic data, comorbidities, COVID-19 disease (diagnosis, presenting symptoms, management, and persistent symptoms), and the return to the usual state of health. Participants were users of social media platforms. We received results from 746 respondents. One hundred thirty-six responses were excluded due to a self-diagnosis of COVID-19. Respondents reporting a COVID-19 diagnosis 3 months or more prior to the study (N = 213) were included in the analysis. Predictors of the delayed return to the usual state of health were identified by logistic regression.

RESULTS: Three months or more after a COVID-19 diagnosis, almost half of the respondents, 109 (51.2%), had residual symptoms. The five most prevalent persistent symptoms were fatigue (13.6%), altered sense of smell (12.7%), muscle aches (10.3%), headache (9.9%), and body aches (8.5%). When questioned regarding the return to baseline health, 152 (71.4%) answered in the affirmative. The total number of chronic medical conditions was determined as a statistically significant predictor for the delayed return to the usual state of health.

CONCLUSION: Three months or more after acute COVID-19 infection, 5 out of 10 survivors experienced persistent symptoms, and 3 out of 10 reported a delayed return to baseline health. Considering the overall burden of COVID-19 disease, this can pose health and socio-economic challenges. Therefore, health systems need support in managing long COVID and improving long-term COVID-19 outcomes.}, } @article {pmid36226148, year = {2022}, author = {Roseti, L and Grigolo, B}, title = {COVID-19 and rheumatic diseases: A mini-review.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {997876}, pmid = {36226148}, issn = {2296-858X}, abstract = {Joint pain and arthralgia can be manifestations of COVID-19, and studies evaluating long COVID symptoms identified the persistence of these disorders. Moreover, some case reports highlighted the development of new inflammatory arthritis in patients with COVID-19, suggesting a possible relation. Viral infections and rheumatic diseases share a documented relationship; they have been associated with genetic and environmental risk factors responsible for some of them. There is crosstalk between viruses and the immune system during the development of several rheumatic diseases. Moreover, infections may participate in the pathogenesis of autoimmune rheumatic diseases and contribute to patient mortality. Therefore, it is crucial to provide a clearer insight into the interaction between viral infections and rheumatic diseases. Here, we provide a mini-review of the current literature with the aim of shedding light on the relationship between COVID-19 and rheumatic or musculoskeletal diseases, which is still unclear. Specifically, we examined several aspects: risk for the rheumatic population of acquiring the virus or developing severe symptoms, similarities of COVID-19 and arthritis, the possible rheumatic consequence of COVID-19, of rheumatic drugs and vaccines, and COVID-19 prevention in rheumatic patients through vaccination.}, } @article {pmid36225258, year = {2022}, author = {Li, Q and Liu, Y and Zhang, L}, title = {Cytoplasmic tail determines the membrane trafficking and localization of SARS-CoV-2 spike protein.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {1004036}, pmid = {36225258}, issn = {2296-889X}, abstract = {The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry through associating with ACE2 on host cells. Intracellular trafficking and palmitoylation of S protein are required for its function. The short cytoplasmic tail of S protein plays a key role in the intracellular trafficking, which contains the binding site for the host trafficking proteins such as COPI, COPII and SNX27. This cytoplasmic tail also contains the palmitoylation sites of S protein. Protein palmitoylation modification of S protein could be catalyzed by a family of zinc finger DHHC domain-containing protein palmitoyltransferases (ZDHHCs). The intracellular trafficking and membrane location facilitate surface expression of S protein and assembly of progeny virions. In this review, we summarize the function of S protein cytoplasmic tail in transportation and localization. S protein relies on intracellular trafficking pathways and palmitoylation modification to facilitate the life cycle of SARS-CoV-2, meanwhile it could interfere with the host transport pathways. The interplay between S protein and intracellular trafficking proteins could partially explain the acute symptoms or Long-COVID complications in multiple organs of COVID-19 patients.}, } @article {pmid36224705, year = {2023}, author = {Arjun, MC and Singh, AK and Roy, P and Ravichandran, M and Mandal, S and Pal, D and Das, K and Gajjala, A and Venkateshan, M and Mishra, B and Patro, BK and Mohapatra, PR and Subba, SH}, title = {Long COVID following Omicron wave in Eastern India-A retrospective cohort study.}, journal = {Journal of medical virology}, volume = {95}, number = {1}, pages = {e28214}, pmid = {36224705}, issn = {1096-9071}, mesh = {Adult ; Humans ; *Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Retrospective Studies ; *COVID-19/epidemiology ; SARS-CoV-2 ; India/epidemiology ; }, abstract = {Long coronavirus disease (COVID) or postacute sequelae of coronavirus disease of 2019 (COVID-19) is widely reported but the data of long COVID after infection with the Omicron variant is limited. This study was conducted to estimate the incidence, characteristics of symptoms, and predictors of long COVID among COVID-19 patients diagnosed during the Omicron wave in Eastern India. The cohort of COVID-19 patients included were adults (≥18 years) diagnosed as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction. After 28 days of diagnosis; participants were followed up with a telephonic interview to capture data on sociodemographic, clinical history, anthropometry, substance use, COVID-19 vaccination status, acute COVID-19 symptoms, and long COVID symptoms. The long COVID symptoms were self-reported by the participants. Logistic regression was used to determine the predictors of long COVID. The median follow-up of participants was 73 days (Interquartile range; 67-83). The final analysis had 524 participants' data; among them 8.2% (95% Confidence Interval [CI]: 6%-10.9%) self-reported long COVID symptoms. Fatigue (34.9%) was the most common reported symptom followed by cough (27.9%). In multivariable logistic regression only two predictors were statistically significant-number of acute COVID-19 symptoms ≥ five (Adjusted odds ratio (aOR) = 2.95, 95% CI: 1.30-6.71) and past history of COVID-19 (aOR = 2.66, 95% CI: 1.14-6.22). The proportion of self-reported long COVID is considerably low among COVID-19 patients diagnosed during the Omicron wave in Eastern India when compared with estimates during Delta wave in the same setting.}, } @article {pmid36224173, year = {2022}, author = {Hastie, CE and Lowe, DJ and McAuley, A and Winter, AJ and Mills, NL and Black, C and Scott, JT and O'Donnell, CA and Blane, DN and Browne, S and Ibbotson, TR and Pell, JP}, title = {Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5663}, pmid = {36224173}, issn = {2041-1723}, support = {COV/LTE/20/06/CSO_/Chief Scientist Office/United Kingdom ; CH/F/21/90010/BHF_/British Heart Foundation/United Kingdom ; RG/20/10/34966/BHF_/British Heart Foundation/United Kingdom ; RE/18/5/34216/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Female ; Hospitalization ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.}, } @article {pmid36223804, year = {2023}, author = {Ortega-Paz, L and Talasaz, AH and Sadeghipour, P and Potpara, TS and Aronow, HD and Jara-Palomares, L and Sholzberg, M and Angiolillo, DJ and Lip, GYH and Bikdeli, B}, title = {COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.}, journal = {Seminars in thrombosis and hemostasis}, volume = {49}, number = {8}, pages = {816-832}, doi = {10.1055/s-0042-1757634}, pmid = {36223804}, issn = {1098-9064}, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; *Pulmonary Embolism/diagnosis/epidemiology/etiology ; *Venous Thrombosis/drug therapy ; Lung ; *Venous Thromboembolism/diagnosis/drug therapy/epidemiology ; *Thrombosis/drug therapy ; Anticoagulants/therapeutic use ; COVID-19 Testing ; }, abstract = {COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.}, } @article {pmid36223711, year = {2022}, author = {Portacci, A and Quaranta, VN and Iorillo, I and Buonamico, E and Diaferia, F and Quaranta, S and Locorotondo, C and Dragonieri, S and Carpagnano, GE}, title = {The impact of healthcare setting on post-COVID mood disorders: a single-centre perspective from Southern Italy Respiratory Intensive Care Unit.}, journal = {Respiratory medicine}, volume = {203}, number = {}, pages = {107006}, pmid = {36223711}, issn = {1532-3064}, mesh = {Humans ; Female ; *COVID-19/complications/epidemiology ; Mood Disorders/epidemiology/etiology ; Prospective Studies ; Intensive Care Units ; Delivery of Health Care ; }, abstract = {BACKGROUND AND OBJECTIVES: Post-COVID syndrome includes several clinical identities, with both physical and mental alterations lasting several months from the acute phase of COVID-19 disease. However, to date, data concerning the relationship between healthcare settings during COVID-19 disease and post-COVID mood disorders are lacking.

METHODS: We performed a prospective study enrolling 440 patients with post-COVID syndrome. Each patient underwent a complete clinical evaluation, along with blood and functional tests. Patients were divided according to the healthcare setting needed during COVID-19 disease.

RESULTS: Patients admitted to RICU were more prone to develop mental alterations, even when compared to ICU-admitted patients. Other risk factors for mood disorders included female gender and some post-COVID symptoms.

CONCLUSIONS: Healthcare needs during COVID-19 can explain the higher incidence of mood disorders in post-COVID syndrome. RICU arises as an important but underexplored risk factor for post-COVID psychic sequelae.}, } @article {pmid36223120, year = {2022}, author = {Durstenfeld, MS and Sun, K and Tahir, P and Peluso, MJ and Deeks, SG and Aras, MA and Grandis, DJ and Long, CS and Beatty, A and Hsue, PY}, title = {Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis.}, journal = {JAMA network open}, volume = {5}, number = {10}, pages = {e2236057}, pmid = {36223120}, issn = {2574-3805}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; *COVID-19/complications/diagnosis ; Cross-Sectional Studies ; Exercise Test ; Humans ; Oxygen ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Reduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.

OBJECTIVES: To estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.

DATA SOURCES: A search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.

STUDY SELECTION: Studies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V̇o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.

DATA EXTRACTION AND SYNTHESIS: Data extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.

MAIN OUTCOMES AND MEASURES: Difference in peak V̇o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.

RESULTS: A total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V̇o2 was -4.9 (95% CI, -6.4 to -3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.

CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.}, } @article {pmid36221293, year = {2022}, author = {Büttiker, P and Stefano, GB and Weissenberger, S and Ptacek, R and Anders, M and Raboch, J and Kream, RM}, title = {HIV, HSV, SARS-CoV-2 and Ebola Share Long-Term Neuropsychiatric Sequelae.}, journal = {Neuropsychiatric disease and treatment}, volume = {18}, number = {}, pages = {2229-2237}, pmid = {36221293}, issn = {1176-6328}, abstract = {Long COVID, in which disease-related symptoms persist for months after recovery, has led to a revival of the discussion of whether neuropsychiatric long-term symptoms after viral infections indeed result from virulent activity or are purely psychological phenomena. In this review, we demonstrate that, despite showing differences in structure and targeting, many viruses have highly similar neuropsychiatric effects on the host. Herein, we compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus 1 (HIV-1), Ebola virus disease (EVD), and herpes simplex virus 1 (HSV-1). We provide evidence that the mutual symptoms of acute and long-term anxiety, depression and post-traumatic stress among these viral infections are likely to result from primary viral activity, thus suggesting that these viruses share neuroinvasive strategies in common. Moreover, it appears that secondary induced environmental stress can lead to the emergence of psychopathologies and increased susceptibility to viral (re)infection in infected individuals. We hypothesize that a positive feedback loop of virus-environment-reinforced systemic responses exists. It is surmised that this cycle of primary virulent activity and secondary stress-induced reactivation, may be detrimental to infected individuals by maintaining and reinforcing the host's immunocompromised state of chronic inflammation, immunological strain, and maladaptive central-nervous-system activity. We propose that this state can lead to perturbed cognitive processing and promote aversive learning, which may manifest as acute, long-term neuropsychiatric illness.}, } @article {pmid36220753, year = {2022}, author = {Ruenjaiman, V and Sodsai, P and Kueanjinda, P and Bunrasmee, W and Klinchanhom, S and Reantragoon, R and Tunvirachaisakul, C and Manothummetha, K and Mejun, N and Liengswangwong, K and Torvorapanit, P and Paitoonpong, L and Putcharoen, O and Palaga, T and Hirankarn, N and , }, title = {Impact of SARS-CoV-2 infection on the profiles and responses of innate immune cells after recovery.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {55}, number = {6 Pt 1}, pages = {993-1004}, pmid = {36220753}, issn = {1995-9133}, mesh = {Humans ; *COVID-19 ; Tumor Necrosis Factor-alpha ; Leukocytes, Mononuclear ; Post-Acute COVID-19 Syndrome ; Longitudinal Studies ; Interleukin-6 ; SARS-CoV-2 ; Cytokines ; Immunity, Innate ; }, abstract = {BACKGROUNDS: SARS-CoV-2 infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic to severe symptoms and death. Most COVID-19 pathogenesis is associated with hyperinflammatory conditions driven primarily by myeloid cell lineages. The long-term effects of SARS-CoV-2 infection post recovery include various symptoms.

METHODS: We performed a longitudinal study of the innate immune profiles 1 and 3 months after recovery in the Thai cohort by comparing patients with mild, moderate, and severe clinical symptoms using peripheral blood mononuclear cells (n = 62).

RESULTS: Significant increases in the frequencies of monocytes compared to controls and NK cells compared to mild and moderate patients were observed in severe patients 1-3 months post recovery. Increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were observed in all recovered patients, even after 3 months. Increased IL-6 and TNFα levels in monocytes were observed 1 month after recovery in response to lipopolysaccharide (LPS) stimulation, while decreased CD86 and HLA-DR levels were observed regardless of stimulation. A multiplex analysis of serum cytokines performed at 1 month revealed that most innate cytokines, except for TNFα, IL4/IL-13 (Th2) and IFNγ (Th1), were elevated in recovered patients in a severity-dependent manner. Finally, the myelopoiesis cytokines G-CSF and GM-CSF were higher in all patient groups. Increased monocytes and IL-6- and TNFα-producing cells were significantly associated with long COVID-19 symptoms.

CONCLUSIONS: These results reveal that COVID-19 infection influences the frequencies and functions of innate immune cells for up to 3 months after recovery, which may potentially lead to some of the long COVID symptoms.}, } @article {pmid36220361, year = {2022}, author = {Lai, H and Yang, M and Sun, M and Pan, B and Wang, Q and Wang, J and Tian, J and Ding, G and Yang, K and Song, X and Ge, L}, title = {Risk of incident diabetes after COVID-19 infection: A systematic review and meta-analysis.}, journal = {Metabolism: clinical and experimental}, volume = {137}, number = {}, pages = {155330}, pmid = {36220361}, issn = {1532-8600}, mesh = {Male ; Humans ; Female ; *Diabetes Mellitus, Type 2/epidemiology ; Retrospective Studies ; COVID-19 Testing ; *COVID-19/epidemiology ; Risk Factors ; }, abstract = {BACKGROUND: COVID-19 might be a risk factor for various chronic diseases. However, the association between COVID-19 and the risk of incident diabetes remains unclear. We aimed to meta-analyze evidence on the relative risk of incident diabetes in patients with COVID-19.

METHODS: In this systematic review and meta-analysis, the Embase, PubMed, CENTRAL, and Web of Science databases were searched from December 2019 to June 8, 2022. We included cohort studies that provided data on the number, proportion, or relative risk of diabetes after confirming the COVID-19 diagnosis. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to pool the relative risk with corresponding 95 % confidence intervals. Prespecified subgroup and meta-regression analyses were conducted to explore the potential influencing factors. We converted the relative risk to the absolute risk difference to present the evidence. This study was registered in advance (PROSPERO CRD42022337841).

MAIN FINDINGS: Ten articles involving 11 retrospective cohorts with a total of 47.1 million participants proved eligible. We found a 64 % greater risk (RR = 1.64, 95%CI: 1.51 to 1.79) of diabetes in patients with COVID-19 compared with non-COVID-19 controls, which could increase the number of diabetes events by 701 (558 more to 865 more) per 10,000 persons. We detected significant subgroup effects for type of diabetes and sex. Type 2 diabetes has a higher relative risk than type 1. Moreover, men may be at a higher risk of overall diabetes than women. Sensitivity analysis confirmed the robustness of the results. No evidence was found for publication bias.

CONCLUSIONS: COVID-19 is strongly associated with the risk of incident diabetes, including both type 1 and type 2 diabetes. We should be aware of the risk of developing diabetes after COVID-19 and prepare for the associated health problems, given the large and growing number of people infected with COVID-19. However, the body of evidence still needs to be strengthened.}, } @article {pmid36220127, year = {2022}, author = {Friedman, SA and Masters-Israilov, A and Robbins, MS}, title = {Secondary Headache Disorders: Approach, Workup, and Special Considerations for Select Populations.}, journal = {Seminars in neurology}, volume = {42}, number = {4}, pages = {418-427}, doi = {10.1055/s-0042-1757753}, pmid = {36220127}, issn = {1098-9021}, mesh = {Humans ; Female ; Pregnancy ; Aged ; *COVID-19/complications ; *Headache Disorders, Secondary/diagnosis/etiology/therapy ; Headache/diagnosis/etiology/therapy ; *Pseudotumor Cerebri/complications ; *Pregnancy Complications, Infectious ; Post-Acute COVID-19 Syndrome ; }, abstract = {Headache is one of the most common diagnoses in neurology. A thorough understanding of the clinical presentation of secondary headache, which can be life-threatening, is critical. This review provides an overview of the diagnostic approach to a patient with headache, including discussion of "red," "orange," and "green" flags. We emphasize particular scenarios to help tailor the clinical workup to individual circumstances such as in pregnant women, when particular attention must be paid to the effects of blood pressure and hypercoagulability, as well as in older adults, where there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis. Patients with risk factors for headache secondary to alterations in intracranial pressure, whether elevated (e.g., idiopathic intracranial hypertension) or decreased (e.g., cerebrospinal fluid leak), may require more specific diagnostic testing and treatment. Finally, headache in patients with COVID-19 or long COVID-19 is increasingly recognized and may have multiple etiologies.}, } @article {pmid36219596, year = {2022}, author = {Heaton-Shrestha, C and Torrens-Burton, A and Leggat, F and Islam, I and Busse, M and Jones, F}, title = {Co-designing personalised self-management support for people living with long Covid: The LISTEN protocol.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0274469}, pmid = {36219596}, issn = {1932-6203}, support = {COV-LT2-0009/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/therapy ; Cost-Benefit Analysis ; Humans ; Randomized Controlled Trials as Topic ; *Self-Management ; State Medicine ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long Covid is recognised as a complex condition characterised by multiple, interacting and fluctuating symptoms which impact everyday life in diverse ways. The extent of symptom clusters and variability supports interventions that can accommodate heterogeneity, such as personalised self-management support. This approach is also advocated by people living with long Covid and guidelines published by the UK's National Institute for Health and Care Excellence. Long Covid Personalised Self-managemenT support co-design and EvaluatioN (LISTEN) is one of 15 research projects funded by the UK's National Institute of Health Research long Covid research programme. LISTEN aims to work with people living with or recovered from long Covid to co-design self-management resources, and a training programme for rehabilitation practitioners to deliver personalised support. The intervention will focus on people not hospitalised for Covid. The protocol presented here details the co-design of the LISTEN intervention which, on completion, will be evaluated in a randomised controlled trial.

METHODS: The study will utilise an Accelerated Experience-Based Co-Design approach, and involve 30 people from England and Wales with lived experience of long Covid, and 15 rehabilitation practitioners living with, or supporting people with, long Covid. Through online meetings, participants will share their stories of long Covid, their challenges and strategies to live better with or recover from long Covid, their priorities for self-management resources and the practitioner training andcreate, review and refine these resources and the training. Throughout, LISTEN will draw upon the UK standards of public involvement in research.

DISCUSSION: If effective and cost-effective, the intervention will be available across the UK's National Health Service. The first of its kind, this study could make a difference to the lives of people with long Covid. To ensure impact, we have developed strategies to involve people from diverse backgrounds and mitigate potential barriers to involvement.}, } @article {pmid36219031, year = {2022}, author = {Cutler, DM}, title = {The Costs of Long COVID.}, journal = {JAMA health forum}, volume = {3}, number = {5}, pages = {e221809}, doi = {10.1001/jamahealthforum.2022.1809}, pmid = {36219031}, issn = {2689-0186}, mesh = {*COVID-19/complications ; Costs and Cost Analysis ; Humans ; Pandemics ; *Pneumonia, Viral/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36218967, year = {2022}, author = {Stephenson, J}, title = {Biden Administration Outlines Strategy to Tackle Long COVID.}, journal = {JAMA health forum}, volume = {3}, number = {4}, pages = {e221280}, doi = {10.1001/jamahealthforum.2022.1280}, pmid = {36218967}, issn = {2689-0186}, mesh = {*COVID-19/complications ; Humans ; Politics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36217108, year = {2022}, author = {Patel, MA and Knauer, MJ and Nicholson, M and Daley, M and Van Nynatten, LR and Martin, C and Patterson, EK and Cepinskas, G and Seney, SL and Dobretzberger, V and Miholits, M and Webb, B and Fraser, DD}, title = {Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {28}, number = {1}, pages = {122}, pmid = {36217108}, issn = {1528-3658}, mesh = {*Biomarkers/blood ; *COVID-19/complications ; Case-Control Studies ; Endoglin ; Female ; Humans ; Integrin alpha4beta1 ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 1 ; Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1 ; Thrombomodulin ; Vascular Cell Adhesion Molecule-1 ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor D ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID is characterized by prolonged, diffuse symptoms months after acute COVID-19. Accurate diagnosis and targeted therapies for Long-COVID are lacking. We investigated vascular transformation biomarkers in Long-COVID patients.

METHODS: A case-control study utilizing Long-COVID patients, one to six months (median 98.5 days) post-infection, with multiplex immunoassay measurement of sixteen blood biomarkers of vascular transformation, including ANG-1, P-SEL, MMP-1, VE-Cad, Syn-1, Endoglin, PECAM-1, VEGF-A, ICAM-1, VLA-4, E-SEL, thrombomodulin, VEGF-R2, VEGF-R3, VCAM-1 and VEGF-D.

RESULTS: Fourteen vasculature transformation blood biomarkers were significantly elevated in Long-COVID outpatients, versus acutely ill COVID-19 inpatients and healthy controls subjects (P < 0.05). A unique two biomarker profile consisting of ANG-1/P-SEL was developed with machine learning, providing a classification accuracy for Long-COVID status of 96%. Individually, ANG-1 and P-SEL had excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, P < 0.0001; validated in a secondary cohort). Specific to Long-COVID, ANG-1 levels were associated with female sex and a lack of disease interventions at follow-up (P < 0.05).

CONCLUSIONS: Long-COVID patients suffer prolonged, diffuse symptoms and poorer health. Vascular transformation blood biomarkers were significantly elevated in Long-COVID, with angiogenesis markers (ANG-1/P-SEL) providing classification accuracy of 96%. Vascular transformation blood biomarkers hold potential for diagnostics, and modulators of angiogenesis may have therapeutic efficacy.}, } @article {pmid36217029, year = {2023}, author = {Kim, DK and Weller, B and Lin, CW and Sheykhkarimli, D and Knapp, JJ and Dugied, G and Zanzoni, A and Pons, C and Tofaute, MJ and Maseko, SB and Spirohn, K and Laval, F and Lambourne, L and Kishore, N and Rayhan, A and Sauer, M and Young, V and Halder, H and la Rosa, NM and Pogoutse, O and Strobel, A and Schwehn, P and Li, R and Rothballer, ST and Altmann, M and Cassonnet, P and Coté, AG and Vergara, LE and Hazelwood, I and Liu, BB and Nguyen, M and Pandiarajan, R and Dohai, B and Coloma, PAR and Poirson, J and Giuliana, P and Willems, L and Taipale, M and Jacob, Y and Hao, T and Hill, DE and Brun, C and Twizere, JC and Krappmann, D and Heinig, M and Falter, C and Aloy, P and Demeret, C and Vidal, M and Calderwood, MA and Roth, FP and Falter-Braun, P}, title = {A proteome-scale map of the SARS-CoV-2-human contactome.}, journal = {Nature biotechnology}, volume = {41}, number = {1}, pages = {140-149}, pmid = {36217029}, issn = {1546-1696}, support = {//CIHR/Canada ; }, mesh = {Humans ; *SARS-CoV-2/genetics ; *COVID-19/genetics ; Proteome/genetics ; Post-Acute COVID-19 Syndrome ; Virus Replication/genetics ; Ubiquitin Thiolesterase/pharmacology ; }, abstract = {Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions. We find that host proteins genetically associated with comorbidities of severe illness and long COVID are enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, we demonstrate that viral NSP14 activates nuclear factor κB (NF-κB)-dependent transcription, even in the presence of cytokine signaling. Moreover, for several tested host proteins, genetic knock-down substantially reduces viral replication. Additionally, we show for USP25 that this effect is phenocopied by the small-molecule inhibitor AZ1. Our results connect viral proteins to human genetic architecture for COVID-19 severity and offer potential therapeutic targets.}, } @article {pmid36216482, year = {2022}, author = {Ameratunga, R and Woon, ST and Steele, R and Lehnert, K and Leung, E and Brooks, AES}, title = {Critical role of diagnostic SARS-CoV-2 T cell assays for immunodeficient patients.}, journal = {Journal of clinical pathology}, volume = {75}, number = {12}, pages = {793-797}, doi = {10.1136/jcp-2022-208305}, pmid = {36216482}, issn = {1472-4146}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/diagnosis ; Antibodies, Viral ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {After almost 3 years of intense study, the immunological basis of COVID-19 is better understood. Patients who suffer severe disease have a chaotic, destructive immune response. Many patients with severe COVID-19 produce high titres of non-neutralising antibodies, which are unable to sterilise the infection. In contrast, there is increasing evidence that a rapid, balanced cellular immune response is required to eliminate the virus and mitigate disease severity. In the longer term, memory T cell responses, following infection or vaccination, play a critical role in protection against SARS-CoV-2.Given the pivotal role of cellular immunity in the response to COVID-19, diagnostic T cell assays for SARS-CoV-2 may be of particular value for immunodeficient patients. A diagnostic SARS-CoV-2 T cell assay would be of utility for immunocompromised patients who are unable to produce antibodies or have passively acquired antibodies from subcutaneous or intravenous immunoglobulin (SCIG/IVIG) replacement. In many antibody-deficient patients, cellular responses are preserved. SARS-CoV-2 T cell assays may identify breakthrough infections if reverse transcriptase quantitative PCR (RT-qPCR) or rapid antigen tests (RATs) are not undertaken during the window of viral shedding. In addition to utility in patients with immunodeficiency, memory T cell responses could also identify chronically symptomatic patients with long COVID-19 who were infected early in the pandemic. These individuals may have been infected before the availability of reliable RT-qPCR and RAT tests and their antibodies may have waned. T cell responses to SARS-CoV-2 have greater durability than antibodies and can also distinguish patients with infection from vaccinated individuals.}, } @article {pmid36216186, year = {2022}, author = {Bertran, M and Pinto Pereira, SM and Nugawela, MD and Stephenson, T and Shafran, R and Ford, T and Buszewicz, M and Whittaker, E and Heyman, I and Segal, TY and Dalrymple, E and Ladhani, SN}, title = {The relationship between Post COVID symptoms in young people and their parents.}, journal = {The Journal of infection}, volume = {85}, number = {6}, pages = {702-769}, doi = {10.1016/j.jinf.2022.10.005}, pmid = {36216186}, issn = {1532-2742}, support = {MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Adolescent ; *COVID-19 ; Parents ; }, } @article {pmid36215063, year = {2022}, author = {, and Wulf Hanson, S and Abbafati, C and Aerts, JG and Al-Aly, Z and Ashbaugh, C and Ballouz, T and Blyuss, O and Bobkova, P and Bonsel, G and Borzakova, S and Buonsenso, D and Butnaru, D and Carter, A and Chu, H and De Rose, C and Diab, MM and Ekbom, E and El Tantawi, M and Fomin, V and Frithiof, R and Gamirova, A and Glybochko, PV and Haagsma, JA and Haghjooy Javanmard, S and Hamilton, EB and Harris, G and Heijenbrok-Kal, MH and Helbok, R and Hellemons, ME and Hillus, D and Huijts, SM and Hultström, M and Jassat, W and Kurth, F and Larsson, IM and Lipcsey, M and Liu, C and Loflin, CD and Malinovschi, A and Mao, W and Mazankova, L and McCulloch, D and Menges, D and Mohammadifard, N and Munblit, D and Nekliudov, NA and Ogbuoji, O and Osmanov, IM and Peñalvo, JL and Petersen, MS and Puhan, MA and Rahman, M and Rass, V and Reinig, N and Ribbers, GM and Ricchiuto, A and Rubertsson, S and Samitova, E and Sarrafzadegan, N and Shikhaleva, A and Simpson, KE and Sinatti, D and Soriano, JB and Spiridonova, E and Steinbeis, F and Svistunov, AA and Valentini, P and van de Water, BJ and van den Berg-Emons, R and Wallin, E and Witzenrath, M and Wu, Y and Xu, H and Zoller, T and Adolph, C and Albright, J and Amlag, JO and Aravkin, AY and Bang-Jensen, BL and Bisignano, C and Castellano, R and Castro, E and Chakrabarti, S and Collins, JK and Dai, X and Daoud, F and Dapper, C and Deen, A and Duncan, BB and Erickson, M and Ewald, SB and Ferrari, AJ and Flaxman, AD and Fullman, N and Gamkrelidze, A and Giles, JR and Guo, G and Hay, SI and He, J and Helak, M and Hulland, EN and Kereselidze, M and Krohn, KJ and Lazzar-Atwood, A and Lindstrom, A and Lozano, R and Malta, DC and Månsson, J and Mantilla Herrera, AM and Mokdad, AH and Monasta, L and Nomura, S and Pasovic, M and Pigott, DM and Reiner, RC and Reinke, G and Ribeiro, ALP and Santomauro, DF and Sholokhov, A and Spurlock, EE and Walcott, R and Walker, A and Wiysonge, CS and Zheng, P and Bettger, JP and Murray, CJL and Vos, T}, title = {Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.}, journal = {JAMA}, volume = {328}, number = {16}, pages = {1604-1615}, pmid = {36215063}, issn = {1538-3598}, support = {K23 NR019019/NR/NINR NIH HHS/United States ; T32 AI007044/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Bayes Theorem ; *COVID-19/complications/epidemiology ; *Fatigue/epidemiology/etiology ; Pain/epidemiology/etiology ; SARS-CoV-2 ; Syndrome ; *Cognition Disorders/epidemiology/etiology ; *Respiratory Insufficiency/epidemiology/etiology ; Internationality ; Global Health/statistics & numerical data ; Mood Disorders/epidemiology/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).

OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.

Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.

EXPOSURES: Symptomatic SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.

RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.

CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.}, } @article {pmid36215047, year = {2022}, author = {Li, D and Liao, X and Liu, Z and Ma, Z and Dong, J and Zheng, G and Zi, M and Wang, F and He, Q and Li, G and Zhang, Z and Liu, L}, title = {Healthy outcomes of patients with COVID-19 two years after the infection: a prospective cohort study.}, journal = {Emerging microbes & infections}, volume = {11}, number = {1}, pages = {2680-2688}, pmid = {36215047}, issn = {2222-1751}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Prospective Studies ; COVID-19 Testing ; Lung/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; }, abstract = {The long-term effect of coronavirus disease 2019 (COVID-19) has been rarely known. This study aimed to investigate healthy outcomes of COVID-19 survivors up to 2 years after the infection. A total of 155 COVID-19 patients, who were discharged from Shenzhen Third People's Hospital from February 2020 to April 2020, were enrolled and followed up until March 4, 2022. COVID-19 survivors received questionnaires of long COVID symptoms and psychological symptoms, pulmonary function tests, chest computed tomography (CT) scans and routine laboratory tests. Two years after infection, 36.6% of patients had at least one symptom of long COVID. Vision impairment and fatigue were the most common symptom. 35.0% of participants still had at least one psychological symptom of anxiety, depression, post-traumatic stress symptoms, and sleep difficulties. Radiographic abnormalities were presented in 50.7% of patients, with the most common features of fibrosis-like lesions and residual ground-glass opacity. Diffuse dysfunction (24.0%) was the main abnormalities of pulmonary function tests. Most laboratory parameters returned to normal range, while persistent abnormalities in kidney and liver function test were observed in a subset of participants after discharge. Two years after COVID-19 infection, persistent symptoms of long COVID and psychological symptoms, as well as abnormalities in pulmonary function tests and CT, were still common in a subset of recovering individuals. These findings were limited by the lack of a healthy control group and pre-COVID assessments, which should be confirmed by further large-scale studies.}, } @article {pmid36214989, year = {2023}, author = {Roe, K}, title = {SARS-CoV-2 and Toxoplasma gondii shared symptoms suggest muscle cells and neurons are their chronic infection reservoirs.}, journal = {Human cell}, volume = {36}, number = {1}, pages = {483-485}, pmid = {36214989}, issn = {1749-0774}, mesh = {Humans ; *Toxoplasma ; SARS-CoV-2 ; *COVID-19 ; Disease Reservoirs ; Neurons ; Muscle Cells ; }, } @article {pmid36213654, year = {2022}, author = {Visvabharathy, L and Orban, ZS and Koralnik, IJ}, title = {Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1003103}, pmid = {36213654}, issn = {2296-858X}, abstract = {INTRODUCTION: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment.

CASE PRESENTATION: A 37-year-old female with a 7-year history of rheumatoid arthritis enrolled in a COVID-19 research study was found to continuously test SARS-CoV-2 antigen positive in the nasopharynx for 6 months after acute infection. She simultaneously presented with new-onset PASC symptoms including chronic occipital headache and periods of intense fatigue 8 weeks after acute infection. The patient was prescribed nirmatrelvir/ritonavir to treat SARS-CoV-2 persistence at 3.5 months post-acute infection and observed a reduction in PASC symptoms 3 weeks after completing antiviral treatment. After resurgence of PASC symptoms, she stopped treatment with tocilizumab for rheumatoid arthritis to attempt complete SARS-CoV-2 viral clearance. The severity of the patient's PASC symptoms subsequently increased, and she developed new-onset brain fog in addition to previous symptoms, which resolved after resumption of tocilizumab treatment. Assessment of adaptive immune responses demonstrated that nirmatrelvir/ritonavir and tocilizumab treatment decreased antiviral and autoreactive T cell activation. After resuming tocilizumab treatment, the patient's PASC symptoms were significantly reduced, but nasopharyngeal antigen positivity remained.

CONCLUSION: These data suggest that nirmatrelvir/ritonavir should be considered in the treatment of PASC in patients who have SARS-CoV-2 antigen persistence, though care must be taken to monitor the patient for symptom resurgence or viral reactivation. In addition, the IL-6 inhibitor tocilizumab may ameliorate PASC symptoms in patients with persistent headache, fatigue, and brain fog.}, } @article {pmid36213211, year = {2022}, author = {Vannini, L and Laynez-Carnicero, A and Bobis-Alvarez, C and Figueroa-Mora, A and Poncela-Mireles, J and Hernandez, FG}, title = {Accuracy of quality of life questionnaire as a diagnostic tool for SARS-CoV-2 pulmonary sequelae.}, journal = {Medicina clinica (English ed.)}, volume = {159}, number = {7}, pages = {330-333}, pmid = {36213211}, issn = {2387-0206}, abstract = {BACKGROUND: Follow-up after hospital discharge of SARS-CoV-2 survivors represents a huge burden on the healthcare system. We attempt to assess the utility of symptoms and health-related quality of life questionnaire (SF-12) to identify SARS CoV2 pulmonary sequelae.

METHODS: Prospective, non-interventional follow-up study. A cardiopulmonary exercise test, functional respiratory test (PFT), SF12 questionnaire were performed after hospitalization at six months after the first positive PCR smear.

RESULTS: 41 patients were included, female (39%), mean age 57.3 ± 13.7 years. 70% persisted with symptoms. 46% presented a maximum oxygen consumption below 80% of predicted. SF-12 physical domain score was significantly reduced in patients with altered PFT (32.7 vs. 45.9; p < 0.001) and obtained the best sensitivity and specificity to identify PFT alterations (AUC 0.862, Sensitivity 85.7%, Specificity 81.5%).

CONCLUSIONS: SF-12 questionnaire shows high sensitivity and specificity to detect SARS CoV2 survivors with pulmonary function alterations.}, } @article {pmid36213137, year = {2022}, author = {Kompani, K and Deml, MJ and Mahdavian, F and Koval, O and Arora, S and Broqvist, H}, title = {Who Said What: A Multi-Country Content Analysis of European Health Organisations' COVID-19 Social Media Communication.}, journal = {International journal of public health}, volume = {67}, number = {}, pages = {1604973}, pmid = {36213137}, issn = {1661-8564}, mesh = {*COVID-19/complications/epidemiology ; Communication ; *Health Communication ; Humans ; Pandemics ; SARS-CoV-2 ; *Social Media ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objectives: As a risk communication tool, social media was mobilised at an unprecedented level during the COVID-19 pandemic. This study examined health authorities' risk communication on social media in response to the pandemic in 2020. Methods: We analysed 1,633 COVID-19-related posts from 15 social media accounts managed by official health authorities in Germany, Norway, Sweden, Switzerland, and the United Kingdom. Results: The rate at which the authorities posted about COVID-19 on social media fluctuated throughout 2020. Each account's posting frequency peaked between March and May 2020, before dropping considerably during the summer. The messages that the organisations focused on also varied throughout the year but covered most risk communication guidelines. Yet, our analysis highlighted themes that were communicated infrequently, such as long COVID or exercising during the pandemic. Conclusion: With more individuals now following health authorities on social media, platforms such as Instagram hold great potential for future risk communication campaigns and strategies.}, } @article {pmid36212783, year = {2022}, author = {Russell, D and Spence, NJ and Chase, JD and Schwartz, T and Tumminello, CM and Bouldin, E}, title = {Support amid uncertainty: Long COVID illness experiences and the role of online communities.}, journal = {SSM. Qualitative research in health}, volume = {2}, number = {}, pages = {100177}, pmid = {36212783}, issn = {2667-3215}, abstract = {Long COVID is characterized by persistent and debilitating long-term symptoms from COVID-19. Many persons with Long COVID began gathering in online communities during the early phases of the pandemic to share their illness experiences. This qualitative interview study explored the subjective experiences of 20 persons with Long COVID recruited from five online communities. Their understandings of illness and associated implications for social relationships with family and friends, healthcare professionals, and online community members were explored. Three themes were identified from our analysis, including (1) complex and unpredictable illness experienced amid an evolving understanding of the pandemic; (2) frustration, dismissal, and gaslighting in healthcare interactions; and (3) validation and support from online communities. These findings highlight the significant uncertainty that persons with Long COVID navigated, the features of their often dismaying healthcare experiences, and the ways in which online communities aided them in understanding their illness.}, } @article {pmid36212621, year = {2022}, author = {Khan, A and Heide, S and Flatley, A and Khan, A and Nobler, M}, title = {Tinnitus and biopsychosocial ramifications of COVID-19 associated with severe suicide attempt-a case report.}, journal = {Psychiatry research case reports}, volume = {1}, number = {2}, pages = {100067}, pmid = {36212621}, issn = {2773-0212}, abstract = {The COVID-19 disease has been linked to multiple physical and mental health consequences which may be partially attributed to multi-system modulation by inflammatory cytokines. Post-acute sequelae (PASC) of SARS-CoV-2 infection, colloquially known as "Long Covid", has become an established entity. However, screening guidelines and interventions for COVID-19 survivors remain elusive. The neuropsychiatric sequelae of COVID-19 seem to originate from a cumulation of biopsychosocial factors which may predispose individuals to acute psychiatric decompensation irrespective of a previously diagnosed mental illness. We present a case report which illustrates how cognitive issues and medical complaints may negatively interact resulting in significant depression and a severe suicide attempt.}, } @article {pmid36211989, year = {2022}, author = {Calabrese, LH and Calabrese, CM}, title = {Long COVID: defining the role of rheumatology in care and research.}, journal = {The Lancet. Rheumatology}, volume = {4}, number = {12}, pages = {e812-e814}, pmid = {36211989}, issn = {2665-9913}, } @article {pmid36211553, year = {2022}, author = {Murata, N and Yamada, A and Fujito, H and Hashimoto, N and Nagao, T and Tanaka, Y and Fukumoto, K and Arai, R and Wakamatsu, Y and Ebuchi, Y and Monden, M and Kojima, K and Hayashi, K and Gon, Y and Okumura, Y}, title = {Cardiovascular manifestations identified by multi-modality imaging in patients with long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {968584}, pmid = {36211553}, issn = {2297-055X}, abstract = {BACKGROUND: The possibility of permanent cardiovascular damage causing cardiovascular long COVID has been suggested; however, data are insufficient. This study investigated the prevalence of cardiovascular disorders, particularly in patients with cardiovascular long COVID using multi-modality imaging.

METHODS: A total of 584 patients admitted to the hospital due to COVID-19 between January 2020 and September 2021 were initially considered. Upon outpatient follow-up, 52 (9%) were suspected to have cardiovascular long COVID, had complaints of chest pain, dyspnea, or palpitations, and were finally enrolled in this study. This study is registered with the Japanese University Hospital Medical Information Network (UMIN 000047978).

RESULTS: Of 52 patients with long COVID who were followed up in the outpatient clinic for cardiovascular symptoms, cardiovascular disorders were present in 27% (14/52). Among them, 15% (8/52) had myocardial injury, 8% (4/52) pulmonary embolisms, and 4% (2/52) both. The incidence of a severe condition (36% [5/14] vs. 8% [3/38], p = 0.014) and in-hospital cardiac events (71% [10/14] vs. 24% [9/38], p = 0.002) was significantly higher in patients with cardiovascular disorders than in those without. A multivariate logistic regression analysis revealed that a severe condition (OR, 5.789; 95% CI 1.442-45.220; p = 0.017) and in-hospital cardiac events (OR, 8.079; 95% CI 1.306-25.657; p = 0.021) were independent risk factors of cardiovascular disorders in cardiovascular long COVID patients.

CONCLUSIONS: Suspicion of cardiovascular involvement in patients with cardiovascular long COVID in this study was approximately 30%. A severe condition during hospitalization and in-hospital cardiac events were risk factors of a cardiovascular sequalae in CV long COVID patients.}, } @article {pmid36211365, year = {2022}, author = {Bizjak, DA and Stangl, M and Börner, N and Bösch, F and Durner, J and Drunin, G and Buhl, JL and Abendroth, D}, title = {Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1004545}, pmid = {36211365}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers ; C-Reactive Protein ; *COVID-19/complications/diagnosis ; COVID-19 Testing ; Humans ; Interleukin-6 ; *Kynurenine/metabolism ; Middle Aged ; SARS-CoV-2 ; Tryptophan/metabolism ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: In patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples.

MATERIAL AND METHODS: The study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302, 144f/158m, mean age 47.1 ± 18.3 years (range 18-75)). Two further groups were generated based on Group A (n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and Group B (n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms/syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission. In Group B we determined Kyn 4 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva two, three and four months after dismission. We identified 12 patients with Post-COVID symptoms >20 weeks with still significant elevated Kyn-levels.

RESULTS: Mean values for NC used as reference were 2.79 ± 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (r=0.411; p-values <0.001) and CRP (r=0.488, p-values<0.001). Kyn values in Group B (Long-/Post-COVID) showed still significant higher values (8.77 ± 1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range.

CONCLUSION: Serum and saliva Kyn are reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve a useful biomarker for diagnosis and monitoring both Long- and Post-COVID syndrome and its therapy.}, } @article {pmid36210480, year = {2023}, author = {Lara Carrion, L and Bramstedt, KA}, title = {Exploring the ethical complexity of pediatric organ transplant candidates and COVID-19 vaccination: Tensions between autonomy and beneficence, children and parents.}, journal = {Pediatric transplantation}, volume = {27}, number = {1}, pages = {e14408}, pmid = {36210480}, issn = {1399-3046}, mesh = {Child ; Humans ; COVID-19 Vaccines/therapeutic use ; Beneficence ; *Tissue and Organ Procurement ; Post-Acute COVID-19 Syndrome ; Pandemics ; *COVID-19/prevention & control ; *Organ Transplantation ; Vaccination ; Parents ; Transplant Recipients ; }, abstract = {BACKGROUND: POT is emotionally sensitive due to cohort vulnerability, their lack of decisional capacity, and waitlist mortality. The COVID-19 pandemic has added complexity to the setting of pediatric transplantation, as well as living donation, due to tensions about COVID-19 vaccination for recipients, donors, and parent-caregivers.

METHODS: In the context of COVID-19 vaccination, two ethicists present four pediatric donation and transplant dilemmas for ethical exploration and offer guidance to clinical teams, noting that mandates are controversial, and there is no global harmonization regarding requirements.

RESULTS: As with all vaccinations, they are a tool of organ stewardship aimed to optimize outcomes and, in the setting of pediatrics, ensure optimal caregiving for these vulnerable recipients. Current evidence supports the ethical permissibility of COVID-19 vaccination mandates for transplant candidates aged 6 months and older.

CONCLUSION: Our guidance considers the tensions of autonomy and beneficence and the ethical duty of organ stewardship. The harms of being unvaccinated and risking the harms of COVID-19 and long-COVID post-transplant support the ethical permissibility of vaccination mandates in countries where the vaccine has pediatric regulatory approval.}, } @article {pmid36210445, year = {2022}, author = {Batiha, GE and Al-Kuraishy, HM and Al-Gareeb, AI and Welson, NN}, title = {Pathophysiology of Post-COVID syndromes: a new perspective.}, journal = {Virology journal}, volume = {19}, number = {1}, pages = {158}, pmid = {36210445}, issn = {1743-422X}, mesh = {*COVID-19/complications ; Fatigue ; Female ; Histamine Antagonists ; Humans ; Inflammation Mediators ; *Mastocytosis/diagnosis ; SARS-CoV-2 ; }, abstract = {Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients. PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown. Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.}, } @article {pmid36208907, year = {2022}, author = {Leta, V and Boura, I and van Wamelen, DJ and Rodriguez-Violante, M and Antonini, A and Chaudhuri, KR}, title = {Covid-19 and Parkinson's disease: Acute clinical implications, long-COVID and post-COVID-19 parkinsonism.}, journal = {International review of neurobiology}, volume = {165}, number = {}, pages = {63-89}, pmid = {36208907}, issn = {2162-5514}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; *Parkinson Disease/complications ; *Parkinsonian Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The Coronavirus Disease 2019 (Covid-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for the delivery of healthcare and has had a clear impact on people with chronic neurological conditions such as Parkinson's disease (PD). Acute worsening of motor and non-motor symptoms and long-term sequalae have been described during and after SARS-CoV-2 infections in people with Parkinson's (PwP), which are likely to be multifactorial in their origin. On the one hand, it is likely that worsening of symptoms has been related to the viral infection itself, whereas social restrictions imposed over the course of the Covid-19 pandemic might also have had such an effect. Twenty cases of post-Covid-19 para-infectious or post-infectious parkinsonism have been described so far where a variety of pathophysiological mechanisms seem to be involved; however, a Covid-19-induced wave of post-viral parkinsonism seems rather unlikely at the moment. Here, we describe the interaction between SARS-CoV-2 and PD in the short- and long-term and summarize the clinical features of post-Covid-19 cases of parkinsonism observed so far.}, } @article {pmid36208897, year = {2022}, author = {Rota, S and Boura, I and Wan, YM and Lazcano-Ocampo, C and Rodriguez-Violante, M and Antonini, A and Chaudhuri, KR}, title = {Spotlight on non-motor symptoms and Covid-19.}, journal = {International review of neurobiology}, volume = {165}, number = {}, pages = {103-133}, pmid = {36208897}, issn = {2162-5514}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; Quality of Life/psychology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The Coronavirus Disease 2019 (Covid-19) pandemic has profoundly affected the quality of life (QoL) and health of the general population globally over the past 2 years, with a clear impact on people with Parkinson's Disease (PwP, PD). Non-motor symptoms have been widely acknowledged to hold a vital part in the clinical spectrum of PD, and, although often underrecognized, they significantly contribute to patients' and their caregivers' QoL. Up to now, there have been numerous reports of newly emerging or acutely deteriorating non-motor symptoms in PwP who had been infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), while some of these symptoms, like fatigue, pain, depression, anxiety and cognitive impairment, have also been identified as part of the long-COVID syndrome due to their persistent nature. The subjacent mechanisms, mediating the appearance or progression of non-motor symptoms in the context of Covid-19, although probably multifactorial in origin, remain largely unknown. Such mechanisms might be, at least partly, related solely to the viral infection per se or the lifestyle changes imposed during the pandemic, as many of the non-motor symptoms seem to be prevalent even among Covid-19 patients without PD. Here, we summarize the available evidence and implications of Covid-19 in non-motor PD symptoms in the acute and chronic, if applicable, phase of the infection, with a special reference on studies of PwP.}, } @article {pmid36208038, year = {2023}, author = {Merikanto, I and Dauvilliers, Y and Chung, F and Wing, YK and De Gennaro, L and Holzinger, B and Bjorvatn, B and Morin, CM and Penzel, T and Benedict, C and Koscec Bjelajac, A and Chan, NY and Espie, CA and Hrubos-Strøm, H and Inoue, Y and Korman, M and Landtblom, AM and Léger, D and Matsui, K and Mota-Rolim, S and Nadorff, MR and Plazzi, G and Reis, C and Yordanova, J and Partinen, M}, title = {Sleep symptoms are essential features of long-COVID - Comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II).}, journal = {Journal of sleep research}, volume = {32}, number = {1}, pages = {e13754}, pmid = {36208038}, issn = {1365-2869}, mesh = {Humans ; *COVID-19 ; Sleep ; *Disorders of Excessive Somnolence/diagnosis ; Fatigue ; *Sleep Initiation and Maintenance Disorders/etiology/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many people report suffering from post-acute sequelae of COVID-19 or "long-COVID", but there are still open questions on what actually constitutes long-COVID and how prevalent it is. The current definition of post-acute sequelae of COVID-19 is based on voting using the Delphi-method by the WHO post-COVID-19 working group. It emphasizes long-lasting fatigue, shortness of breath and cognitive dysfunction as the core symptoms of post-acute sequelae of COVID-19. In this international survey study consisting of 13,628 subjects aged 18-99 years from 16 countries of Asia, Europe, North America and South America (May-Dec 2021), we show that post-acute sequelae of COVID-19 symptoms were more prevalent amongst the more severe COVID-19 cases, i.e. those requiring hospitalisation for COVID-19. We also found that long-lasting sleep symptoms are at the core of post-acute sequelae of COVID-19 and associate with the COVID-19 severity when COVID-19 cases are compared with COVID-negative cases. Specifically, fatigue (61.3%), insomnia symptoms (49.6%) and excessive daytime sleepiness (35.8%) were highly prevalent amongst respondents reporting long-lasting symptoms after hospitalisation for COVID-19. Understanding the importance of sleep-related symptoms in post-acute sequelae of COVID-19 has a clinical relevance when diagnosing and treating long-COVID.}, } @article {pmid36206959, year = {2022}, author = {Trimarco, V and Izzo, R and Zanforlin, A and Tursi, F and Scarpelli, F and Santus, P and Pennisi, A and Pelaia, G and Mussi, C and Mininni, S and Messina, N and Marazzi, G and Maniscalco, M and Mallardo, M and Fazio, G and Diana, A and Capra Marzani, M and Aloè, T and Mone, P and Trimarco, B and Santulli, G}, title = {Endothelial dysfunction in long-COVID: New insights from the nationwide multicenter LINCOLN Study.}, journal = {Pharmacological research}, volume = {185}, number = {}, pages = {106486}, pmid = {36206959}, issn = {1096-1186}, mesh = {Humans ; *COVID-19 ; Ascorbic Acid ; Antioxidants/metabolism ; Oxidative Stress ; Endothelium, Vascular/metabolism ; Arginine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36206625, year = {2022}, author = {Ackermann, M and Kamp, JC and Werlein, C and Walsh, CL and Stark, H and Prade, V and Surabattula, R and Wagner, WL and Disney, C and Bodey, AJ and Illig, T and Leeming, DJ and Karsdal, MA and Tzankov, A and Boor, P and Kühnel, MP and Länger, FP and Verleden, SE and Kvasnicka, HM and Kreipe, HH and Haverich, A and Black, SM and Walch, A and Tafforeau, P and Lee, PD and Hoeper, MM and Welte, T and Seeliger, B and David, S and Schuppan, D and Mentzer, SJ and Jonigk, DD}, title = {The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling.}, journal = {EBioMedicine}, volume = {85}, number = {}, pages = {104296}, pmid = {36206625}, issn = {2352-3964}, support = {P01 HL146369/HL/NHLBI NIH HHS/United States ; MR/R025673/1/MRC_/Medical Research Council/United Kingdom ; R01 HL060190/HL/NHLBI NIH HHS/United States ; MR/S007687/1/MRC_/Medical Research Council/United Kingdom ; P01 HL134610/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Lung/diagnostic imaging/pathology ; *Lung Diseases, Interstitial/pathology ; Fibrosis ; Biomarkers/analysis ; Ischemia/pathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response.

METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time.

FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19.

INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID.

FUNDING: This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.}, } @article {pmid36204261, year = {2022}, author = {Menezes, AS and Botelho, SM and Santos, LR and Rezende, AL}, title = {Acute COVID-19 Syndrome Predicts Severe Long COVID-19: An Observational Study.}, journal = {Cureus}, volume = {14}, number = {10}, pages = {e29826}, pmid = {36204261}, issn = {2168-8184}, abstract = {Introduction Tissue damage, chronic dysfunction, and symptoms that last more than 12 weeks are hallmarks of long-term chronic opportunistic viral infection (COVID-19), and the disease may have a permanent, relapsing/remitting, or gradually improving course. This study aimed to determine the risk factors of severe long COVID-19. Methods In October 2021, primary care clinics enrolled consenting 18- to 89-year-olds to complete an online questionnaire on self-diagnosis, clinician diagnosis, testing, symptom presence, and duration of COVID-19. Long COVID-19 was identified if symptoms were beyond 12 weeks. Patients with long-lasting COVID-19 symptoms were assessed using multivariable regression to identify potential predictors of severe long COVID-19. Results Of the 220 respondents, 108 (49%) patients were self- or clinician-diagnosed with COVID-19 or had a confirmed positive laboratory test result. Patients aged >45 years and with at least 15 COVID-19 symptoms were 5.55 and 6.02 times, respectively, more likely to acquire severe long COVID-19. Most patients with severe and moderate post-acute COVID-19 syndrome had no relevant comorbidities (p=0.0402; odds ratio [OR]=0.4; 95% confidence interval [CI]=0.18-0.98). Obesity was a significant predictor (p=0.0307; OR=6.2; 95% CI=1.1-33.2). Conclusion The simultaneous presence of 15 or more COVID-19 symptoms, age >45 years, and obesity were related to a higher probability of severe long COVID-19.}, } @article {pmid36203683, year = {2022}, author = {Zhong, H and Zhou, Y and Mei, SY and Tang, R and Feng, JH and He, ZY and Xu, QY and Xing, SP}, title = {Scars of COVID-19: A bibliometric analysis of post-COVID-19 fibrosis.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {967829}, pmid = {36203683}, issn = {2296-2565}, mesh = {Bibliometrics ; *COVID-19/complications/epidemiology ; Cicatrix ; Cytokines ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) becomes a worldwide public health threat. Increasing evidence proves that COVID-19-induced acute injuries could be reversed by a couple of therapies. After that, post-COVID-19 fibrosis (PCF), a sequela of "Long COVID," earns rapidly emerging concerns. PCF is associated with deteriorative lung function and worse quality of life. But the process of PCF remains speculative. Therefore, we aim to conduct a bibliometric analysis to explore the overall structure, hotspots, and trend topics of PCF.

MATERIALS AND METHODS: A comprehensive search was performed in the Web of Science core database to collect literature on PCF. Search syntax included COVID-19 relevant terms: "COVID 19," "COVID-19 Virus Disease," "COVID-19 Virus Infection," "Coronavirus Disease-19," "2019 Novel Coronavirus Disease," "2019 Novel Coronavirus Infection," "SARS Coronavirus 2 Infection," "COVID-19 Pandemic," "Coronavirus," "2019-nCoV," and "SARS-CoV-2"; and fibrosis relevant terms: "Fibrosis," "Fibroses," and "Cirrhosis." Articles in English were included. Totally 1,088 publications were enrolled. Searching results were subsequentially exported and collected for the bibliometric analysis. National, organizational, and individual level data were analyzed and visualized through biblioshiny package in the R, VOSviewer software, the CiteSpace software, and the Graphical Clustering Toolkit (gCLUTO) software, respectively.

RESULTS: The intrinsic structure and development in the field of PCF were investigated in the present bibliometric analysis. The topmost keywords were "COVID-19" (occurrences, 636) surrounded by "SARS-CoV-2" (occurrences, 242), "coronavirus" (occurrences, 123), "fibrosis" (occurrences, 120), and "pneumonia" (occurrences, 94). The epidemiology, physiopathology, diagnosis, and therapy of PCF were extensively studied. After this, based on dynamic analysis of keywords, hot topics sharply changed from "Wuhan," "inflammation," and "cytokine storm" to "quality of life" and "infection" through burst detection; from "acute respiratory syndrome," "cystic-fibrosis" and "fibrosis" to "infection," "COVID-19," "quality-of-life" through thematic evolution; from "enzyme" to "post COVID." Similarly, co-cited references analysis showed that topics of references with most citations shift from "pulmonary pathology" (cluster 0) to "COVID-19 vaccination" (cluster 6). Additionally, the overview of contributors, impact, and collaboration was revealed. Summarily, the USA stood out as the most prolific, influential, and collaborative country. The Udice French Research University, Imperial College London, Harvard University, and the University of Washington represented the largest volume of publications, citations, H-index, and co-authorships, respectively. Dana Albon was the most productive and cited author with the strongest co-authorship link strength. Journal of Cystic Fibrosis topped the list of prolific and influential journals.

CONCLUSION: Outcomes gained from this study assisted professionals in better realizing PCF and would guide future practices. Epidemiology, pathogenesis, and therapeutics were study hotspots in the early phase of PCF research. As the spread of the COVID-19 pandemic and progress in this field, recent attention shifted to the quality of life of patients and post-COVID comorbidities. Nevertheless, COVID-19 relevant infection and vaccination were speculated to be research trends with current and future interest. International cooperation as well as in-depth laboratory experiments were encouraged to promote further explorations in the field of PCF.}, } @article {pmid36202473, year = {2022}, author = {O'Sullivan-Murphy, B and Driehuys, B and Mammarappallil, J}, title = {MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?.}, journal = {Radiologic clinics of North America}, volume = {60}, number = {6}, pages = {1021-1032}, doi = {10.1016/j.rcl.2022.06.007}, pmid = {36202473}, issn = {1557-8275}, mesh = {Humans ; Lung/diagnostic imaging ; *Lung Diseases/diagnostic imaging ; Magnetic Resonance Imaging/methods ; *Xenon Isotopes ; }, abstract = {Patients with diffuse lung diseases require thorough medical and social history and physical examinations, coupled with a multitude of laboratory tests, pulmonary function tests, and radiologic imaging to discern and manage the specific disease. This review summarizes the current state of imaging of various diffuse lung diseases by hyperpolarized MR imaging. The potential of hyperpolarized MR imaging as a clinical tool is outlined as a novel imaging approach that enables further understanding of the cause of diffuse lung diseases, permits earlier detection of disease progression before that found with pulmonary function tests, and can delineate physiologic response to lung therapies.}, } @article {pmid36200625, year = {2022}, author = {Pinto, MD and Chakraborty, R and Lambert, N}, title = {The Elephant in the Waiting Room: An Urgent Call for Papers to Address the Public Health Crisis of Long COVID.}, journal = {Clinical nursing research}, volume = {31}, number = {8}, pages = {1387-1389}, pmid = {36200625}, issn = {1552-3799}, mesh = {Humans ; *COVID-19/epidemiology ; Public Health ; Waiting Rooms ; *Pneumonia, Viral/epidemiology/prevention & control ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36199500, year = {2022}, author = {Herndon, CM and Nguyen, V}, title = {Patterns of Viral Arthropathy and Myalgia Following COVID-19: A Cross-Sectional National Survey.}, journal = {Journal of pain research}, volume = {15}, number = {}, pages = {3069-3077}, pmid = {36199500}, issn = {1178-7090}, abstract = {INTRODUCTION: Viral arthropathy is an increasingly recognized sequela of several viral pathogens including alphaviruses, hepatitis, and potentially coronaviruses. Case reports of viral arthropathy and myalgia associated with SARS-CoV-2 infection (COVID-19) both during active disease and following resolution of acute COVID-19 symptoms are becoming more prevalent. We sought to describe the prevalence of viral arthropathy and myalgia associated with COVID-19, as well as to identify factors that may predict these symptoms.

METHODS: A national, cross-sectional survey was conducted using a questionnaire administered online. Subjects self-reporting previous confirmed COVID-19 were recruited using the Amazon Mechanical Turk crowdsourcing platform. Questionnaire items included demographics, frequency and severity of common COVID-19 symptoms, requirement for hospitalization or mechanical ventilation, subject recall of arthropathy or myalgia onset, duration, and severity, as well as WOMAC score. Binary logistic regression was used to identify potential predictive co-variates for the development of either arthropathy or myalgia.

RESULTS: A total of 3222 participants completed the arthropathy/myalgia questionnaire with 1065 responses remaining for analysis following application of exclusion criteria, data integrity review, and omission of respondents with confounding conditions. Of the 1065 cases, 282 (26.5%) reported arthralgia and 566 (53.2%) reported myalgia at some point during or after COVID-19 with 9.9% and 6.0% reporting onset of arthralgia or myalgia, respectively, after resolution of acute COVID-19 symptoms. The presence of several commonly reported COVID symptoms or indicators of disease severity was predictive of arthralgia including hospitalization (OR 3.7; 95% CI 2.4 to 5.8), sore throat (OR 2.3; 95% CI 1.5 to 3.5), fatigue (OR 2.9; 95% CI 1.7 to 4.9), and ageusia/anosmia (OR 1.7; 95% CI 1.1 to 2.7).

DISCUSSION: Based on these results, new-onset arthropathy and myalgia following COVID-19 resolution may be an increasingly encountered etiology for pain.}, } @article {pmid36198972, year = {2022}, author = {Facharztmagazine, R}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {17}, pages = {70}, doi = {10.1007/s15006-022-1962-0}, pmid = {36198972}, issn = {1613-3560}, mesh = {*COVID-19/complications ; *Cough ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36196947, year = {2022}, author = {Hawar, AS and Dauod, AS}, title = {Long COVID-19 prevalence among a sample of infected people in Erbil city.}, journal = {Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharmacologie clinique}, volume = {29}, number = {3}, pages = {e123-e133}, pmid = {36196947}, issn = {2561-8741}, mesh = {*COVID-19/complications/epidemiology ; Cities ; Cross-Sectional Studies ; Humans ; Prevalence ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-term effects of the disease were founded and described as post-COVID-19 syndrome post-COVID syndrome are the symptoms that develop and last for four weeks or even months and cannot be explained by an alternative diagnosis; symptoms may remain for >3 months. The cause of persistent symptoms is unclear. Objectives: This study aimed to Estimate the prevalence of residual symptoms among a sample of people infected with COVID-19 who survived and recovered in Erbil city and to find out the relation between the severity of the disease and post-COVID-19 syndrome. And to know the incidence of post-COVID-19 syndrome in chronic disease patients.

PATIENTS AND METHODS: This cross-sectional study was conducted in 6 primary health care centers in 6 municipalities in Erbil city, Kurdistan region, Iraq. A convenience sample of randomly selected 300 patients was involved in the study depending on inclusion criteria. For one year, starting from March 1, 2021, until the end of February 2022.

RESULTS: The prevalence of post-COVID syndrome among the 300 cases was 54.67%. Of these cases, 11.7% had one symptom, 26% had two signs, and 17% had with three or more symptoms. There was a significant statistical association between persistent symptoms and the severity of COVID-19. Also, there was a substantial statistical association between persistent symptoms and chronic disease, most (67.9%) respondents with post-COVID-19 syndromes suffered from chronic disease, and the p-value was 0.001. There was a significant statistical association between persistent symptoms and disease duration; most (73%) of cases with post-COVID-19 syndrome got the disease from 7 to 14 days, while 54.5% of them struggled with COVID-19 for >14 days.

CONCLUSION: Most people who have recovered from COVID-19 have many long-lasting symptoms that make it hard to go about their daily lives. This is now called a post-COVID syndrome. Getting to this status could have been caused by several things. Age, gender, whether a person has a chronic disease, disease severity, and duration are all things to consider, Even though all COVID-19 victims should be kept an eye on for long-term evaluation and treatment of post-COVID symptoms.}, } @article {pmid36196612, year = {2022}, author = {Kim, Y and Kim, SE and Kim, T and Yun, KW and Lee, SH and Lee, E and Seo, JW and Jung, YH and Chong, YP}, title = {Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID.}, journal = {Infection & chemotherapy}, volume = {54}, number = {3}, pages = {566-597}, pmid = {36196612}, issn = {2093-2340}, abstract = {Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called 'long COVID' have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.}, } @article {pmid36195985, year = {2023}, author = {Peter, RS and Nieters, A and Brockmann, SO and Göpel, S and Kindle, G and Merle, U and Steinacker, JM and Kern, WV and Rothenbacher, D and , }, title = {Association of BMI with general health, working capacity recovered, and post-acute sequelae of COVID-19.}, journal = {Obesity (Silver Spring, Md.)}, volume = {31}, number = {1}, pages = {43-48}, pmid = {36195985}, issn = {1930-739X}, mesh = {Humans ; Female ; Male ; Adult ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Body Mass Index ; Disease Progression ; Fatigue/epidemiology/etiology ; }, abstract = {OBJECTIVE: The aim of this study was to determine the risk of post-acute sequelae of COVID-19 associated with the continuous spectrum of BMI.

METHODS: Epidemiology of Long COVID (EPILOC) is a population-based study conducted in Baden-Württemberg (Germany), including subjects aged 18 to 65 years who tested positive for SARS-CoV-2 between October 2020 and April 2021. Eligible subjects answered a standardized questionnaire, including sociodemographic characteristics, lifestyle factors, and the presence of specific symptoms. Participants assessed their current general health recovery and working capacity compared with the pre-infection situation and provided their body height and weight. Generalized additive models were used to assess the association of BMI with general health recovered, working capacity recovered, and prevalence of fatigue, cognitive impairment, and chest symptoms.

RESULTS: The analyses included 11,296 individuals (41% male), with a mean age of 44.0 (SD 13.7) years. Best general health recovery was observed at BMI of 22.1 (95% CI: 21.0-27.0) kg/m[2] in men and BMI of 21.6 (95% CI: 20.3-23.1) kg/m[2] in women. In addition, we found that increasing BMI was consistently associated with post-COVID fatigue, neurocognitive impairment, and chest symptoms.

CONCLUSIONS: High BMI contributes to impaired recovery after SARS-CoV-2 infection; however, a low BMI is associated with impaired recovery as well.}, } @article {pmid36195306, year = {2022}, author = {Hung, CH and Wei, JC}, title = {Long COVID symptoms survey and methodological issue.}, journal = {Pharmacological research}, volume = {185}, number = {}, pages = {106485}, doi = {10.1016/j.phrs.2022.106485}, pmid = {36195306}, issn = {1096-1186}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36194958, year = {2023}, author = {Tíscar-González, V and Sánchez-Gómez, S and Lafuente Martínez, A and Peña Serrano, A and Twose López, M and Díaz Alonso, S and Bartolomé-Rupérez, M and Portuondo-Jiménez, J and Zorrilla-Martínez, I}, title = {[Experiences and impact on the quality of life of people with long COVID].}, journal = {Gaceta sanitaria}, volume = {37}, number = {}, pages = {102247}, doi = {10.1016/j.gaceta.2022.102247}, pmid = {36194958}, issn = {1578-1283}, mesh = {Humans ; Infant ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Qualitative Research ; }, abstract = {OBJECTIVE: To explore the experiences of people with persistent COVID in the Basque Country more than a year after the start of the pandemic, in order to understand the health and social impact it has, as well as to detect possible areas for improvement in the care that these people receive in order to develop health programms to support their recovery.

METHOD: Qualitative phenomenological study. In-depth interviews will be carried out as a data collection technique until saturation of the discourse. Patients of legal age who present persistent COVID symptomatology with an evolution time of more than 12 weeks were included. Contact with the patients was made through the Basque Long COVID Collective. The interviews were carried out and recorded through the ZOOM application. After the literal transcription of the interviews, the thematic analysis will be carried out, identifying the first units of meaning and assigning codes that will later be grouped into the different categories.

RESULTS: 20 patients participated. A total of three main categories emerged from the analysis of the discourses: 1) affecting/impacting patients' quality of life; 2) identifying improvements in healthcare; and 3) comforting aspects.

CONCLUSIONS: This study shows the significant impact on the quality of life suffered by these people. It is necessary to design health policies that favour a personalised, comprehensive and multidisciplinary approach to these patients.}, } @article {pmid36194229, year = {2022}, author = {Slomski, A}, title = {Long COVID in Children.}, journal = {JAMA}, volume = {328}, number = {13}, pages = {1288}, doi = {10.1001/jama.2022.15439}, pmid = {36194229}, issn = {1538-3598}, mesh = {*COVID-19/complications ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36193427, year = {2022}, author = {Ozduran, E and Büyükçoban, S}, title = {A content analysis of the reliability and quality of Youtube videos as a source of information on health-related post-COVID pain.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e14089}, pmid = {36193427}, issn = {2167-8359}, mesh = {United States ; Humans ; *COVID-19/epidemiology ; Reproducibility of Results ; Information Dissemination ; *Social Media ; Post-Acute COVID-19 Syndrome ; Information Sources ; Quality of Life ; Pain ; }, abstract = {BACKGROUND: The use of the internet as a source of information has increased during the pandemic, and YouTube has become an increasingly important source of information on Coronavirus disease 2019 (COVID-19). In the long COVID picture, which occurs when symptoms related to COVID-19 last longer than 1 month, pain involving the musculoskeletal system affects the quality of life quite negatively. The aim of this study was to investigate the informational value and quality of YouTube videos related to post-COVID pain.

METHODS: In this study, 180 videos were listed using the search terms "pain after COVID," "post-COVID pain," and "long COVID and pain"(15 April 2022). Videos were classified according to video parameters and content analysis. Quality, reliability and accuracy of the videos were determined with the Global Quality Score (GQS), the Journal of American Medical Association (JAMA) Benchmark Criteria and the Modified DISCERN Questionnaire, respectively.

RESULTS: One hundred videos that met the inclusion criteria were included in the assessment. Of these videos, 74 were found to be of low quality, 14 of moderate quality, and 12 of high quality; 21% contained insufficient data, 73% contained partially sufficient data, and 6% contained completely sufficient data. Videos uploaded by academic sources (66.7%) and physicians (12.5%) made up the majority of the high-quality group. A statistically significant correlation was found between the source of upload and number of views (p = 0.014), likes (p = 0.030), comments (p = 0.007), and video duration (p = 0.004). Video duration was found to have a poor positive correlation with GQS (r = 0.500), JAMA (r = 0.528), and modified DISCERN (r = 0.470) scores (p < 0.001).

CONCLUSION: The findings of this study revealed that the majority of YouTube videos on post-COVID pain had low quality and partially sufficient data. High-quality videos were found to have longer durations and were uploaded by academic sources and physicians. The fact that only videos with English content at a certain time can be counted among the limitations. For patients suffering from post-COVID pain whose access to healthcare services was interrupted during the COVID pandemic, YouTube can be considered as an alternative source as well as a means of telerehabilitation. It can be argued that higher quality videos created by healthcare professionals could aid in patient education in the future.}, } @article {pmid36192556, year = {2022}, author = {}, title = {Long-term neurological sequelae of SARS-CoV-2 infection.}, journal = {Nature medicine}, volume = {28}, number = {11}, pages = {2269-2270}, pmid = {36192556}, issn = {1546-170X}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Nervous System Diseases/etiology ; Disease Progression ; }, abstract = {We show that patients who survive the first 30 days of acute SARS-CoV-2 infection have an increased risk of various post-acute neurological disorders after 1 year compared with uninfected contemporaries. The burden of these sequelae (aspects of ‘long COVID’) has serious implications for patients as well as society.}, } @article {pmid36191881, year = {2022}, author = {Santulli, G and Trimarco, V and Trimarco, B and Izzo, R}, title = {Beneficial effects of Vitamin C and L-Arginine in the treatment of post-acute sequelae of COVID-19.}, journal = {Pharmacological research}, volume = {185}, number = {}, pages = {106479}, pmid = {36191881}, issn = {1096-1186}, mesh = {Humans ; *Ascorbic Acid/therapeutic use/pharmacology ; *COVID-19/complications ; Arginine/therapeutic use/pharmacology ; Vasodilation ; *COVID-19 Drug Treatment ; }, } @article {pmid36191820, year = {2022}, author = {Daitch, V and Yelin, D and Awwad, M and Guaraldi, G and Milić, J and Mussini, C and Falcone, M and Tiseo, G and Carrozzi, L and Pistelli, F and Nehme, M and Guessous, I and Kaiser, L and Vetter, P and Bordas-Martínez, J and Durà-Miralles, X and Peleato-Catalan, D and Gudiol, C and Shapira-Lichter, I and Abecasis, D and Leibovici, L and Yahav, D and Margalit, I and , }, title = {Characteristics of long-COVID among older adults: a cross-sectional study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {125}, number = {}, pages = {287-293}, doi = {10.1016/j.ijid.2022.09.035}, pmid = {36191820}, issn = {1878-3511}, mesh = {Female ; Aged ; Humans ; Middle Aged ; *Post-Acute COVID-19 Syndrome ; Cross-Sectional Studies ; *COVID-19/epidemiology ; COVID-19 Testing ; Prospective Studies ; Dyspnea/etiology ; Fatigue/etiology ; Obesity ; }, abstract = {OBJECTIVES: To describe long-COVID symptoms among older adults and to assess the risk factors for two common long-COVID symptoms: fatigue and dyspnea.

METHODS: This is a multicenter, prospective cohort study conducted in Israel, Switzerland, Spain, and Italy. Individuals were included at least 30 days after their COVID-19 diagnosis. We compared long-COVID symptoms between elderly (aged >65 years) and younger individuals (aged 18-65 years) and conducted univariate and multivariable analyses for the predictors of long-COVID fatigue and dyspnea.

RESULTS: A total of 2333 individuals were evaluated at an average of 5 months (146 days [95% confidence interval 142-150]) after COVID-19 onset. The mean age was 51 years, and 20.5% were aged >65 years. Older adults were more likely to be symptomatic, with the most common symptoms being fatigue (38%) and dyspnea (30%); they were more likely to complain of cough and arthralgia and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor.

CONCLUSION: Older individuals with long-COVID have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.}, } @article {pmid36191007, year = {2022}, author = {Smyth, N and Alwan, NA and Band, R and Chaudhry, A and Chew-Graham, CA and Gopal, D and Jackson, M and Kingstone, T and Wright, A and Ridge, D}, title = {Exploring the lived experience of Long Covid in black and minority ethnic groups in the UK: Protocol for qualitative interviews and art-based methods.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275166}, pmid = {36191007}, issn = {1932-6203}, support = {NIHR203106/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; *Ethnicity ; Humans ; Minority Groups ; Qualitative Research ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Some people experience prolonged symptoms following an acute COVID-19 infection including fatigue, chest pain and breathlessness, headache and cognitive impairment. When symptoms persist for over 12 weeks following the initial infection, and are not explained by an alternative diagnosis, the term post-COVID-19 syndrome is used, or the patient-defined term of Long Covid. Understanding the lived experiences of Long Covid is crucial to supporting its management. However, research on patient experiences of Long Covid is currently not ethnically diverse enough. The study aim is to explore the lived experience of Long Covid, using qualitative interviews and art-based methods, among people from ethnically diverse backgrounds (in the UK), to better understand wider systems of support and healthcare support needs. Co-created artwork will be used to build on the interview findings. A purposive sampling strategy will be used to gain diverse experiences of Long Covid, sampling by demographics, geographic locations and experiences of Long Covid. Individuals (aged >18 years) from Black and ethnic minority backgrounds, who self-report Long Covid symptoms, will be invited to take part in a semi-structured interview. Interviews will be analysed thematically. A sub-sample of participants will be invited to co-create visual artwork to further explore shared narratives of Long Covid, enhance storytelling and increase understanding about the condition. A patient advisory group, representing diversity in ethnicity and experiences of Long Covid, will inform all research stages. Stakeholder workshops with healthcare professionals and persons, systems or networks important to people's management of Long Covid, will advise on the integration of findings to inform management of Long Covid. The study will use patient narratives from people from diverse ethnic backgrounds, to raise awareness of Long Covid and help inform management of Long Covid and how wider social systems and networks may inform better healthcare service access and experiences.}, } @article {pmid36190929, year = {2022}, author = {Baig, AM and Greig, NH and Gerlach, J and Salunke, P and Fabrowski, M and Viduto, V and Ali, T}, title = {Underlying Causes and Treatment Modalities for Neurological Deficits in COVID-19 and Long-COVID.}, journal = {ACS chemical neuroscience}, volume = {13}, number = {20}, pages = {2934-2938}, doi = {10.1021/acschemneuro.2c00482}, pmid = {36190929}, issn = {1948-7193}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {With reports of diverse neurological deficits in the acute phase of COVID-19, there is a surge in neurological findings in Long-COVID─a protracted phase of SARS-CoV-2 infection. Very little is known regarding the pathogenic mechanisms of Neuro-COVID in the above two settings in the current pandemic. Herein, we hint toward the possible molecular mechanism that can contribute to the signs and symptoms of patients with neurological deficits and possible treatment and prevention modalities in the acute and chronic phases of COVID-19.}, } @article {pmid36189287, year = {2022}, author = {Teo, WP and Goodwill, AM}, title = {Can exercise attenuate the negative effects of long COVID syndrome on brain health?.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {986950}, pmid = {36189287}, issn = {1664-3224}, mesh = {Brain/physiology ; Brain-Derived Neurotrophic Factor ; *COVID-19/complications ; Exercise/physiology ; Humans ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {The impetus for many governments globally to treat the novel coronavirus (COVID-19) as an endemic warrant more research into the prevention, and management of long COVID syndrome (LCS). Whilst the data on LCS remains scarce, reports suggest a large proportion of recovered individuals will experience ongoing neuropsychological symptoms, even with mild disease severity. The pathophysiology underlying LCS is multifaceted. Evidence suggests that altered inflammatory, neurotrophic, and neurotransmitter pathways within the brain contribute to neuropsychological symptoms reported following COVID-19. Exercise or regular physical activity has long been shown to have positive effects on brain health and cognition through exerting positive effects on inflammatory markers, neurotransmitters, and neurotropic factors analogous to the neurophysiological pathways proposed to be disrupted by COVID-19 infection. Thus, exercise may serve as an important lifestyle behavior in the management of LCS. In this opinion article, we present the evidence to support the positive role of exercise in the management of cognitive symptom that manifest with LCS and discuss important considerations and interactions with cardiorespiratory and exercise tolerance complications that often present for individuals experiencing LCS. We highlight the need for more research and training of sports medicine practitioners and clinical exercise physiologists in the management of LCS with exercise and call for further research to understand the optimal dose-responses and exercise prescription guidelines for cognitive benefits and minimizing other complications.}, } @article {pmid36189286, year = {2022}, author = {Lv, Y and Zhang, T and Cai, J and Huang, C and Zhan, S and Liu, J}, title = {Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {952987}, pmid = {36189286}, issn = {1664-3224}, mesh = {*COVID-19/complications/genetics ; Computational Biology ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/genetics ; Humans ; Interleukin-6 ; *MicroRNAs ; Pandemics ; SARS-CoV-2 ; Systems Biology ; Transcription Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear.

METHODS: We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein-protein interaction (PPI) analysis, transcription factor (TF)-gene interaction network analysis, transcription factor-miRNA co-regulatory network analysis, and candidate drug analysis prediction.

RESULTS: We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF-gene and TF-miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted.

CONCLUSION: This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.}, } @article {pmid36188789, year = {2021}, author = {Curnow, E and Tyagi, V and Salisbury, L and Stuart, K and Melville-Jóhannesson, B and Nicol, K and McCormack, B and Dewing, J and Magowan, R and Sagan, O and Bulley, C}, title = {Person-Centered Healthcare Practice in a Pandemic Context: An Exploration of People's Experience of Seeking Healthcare Support.}, journal = {Frontiers in rehabilitation sciences}, volume = {2}, number = {}, pages = {726210}, pmid = {36188789}, issn = {2673-6861}, support = {COV/QMU/20/04/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {Background: The recent COVID-19 pandemic increased pressure upon healthcare resources resulting in compromised health services. Enforced national lockdown led to people being unable to access essential services in addition to limiting contact with social support networks. The novel coronavirus, and subsequent condition known as long covid were not well-understood and clinicians were not supported by existing guidelines or pathways. Our study explored people's experiences of healthcare during this period with a person-centered "lens." Methods: Ninety-seven people participated in our online survey about their experiences of the pandemic, particularly while socially isolated and their experiences of healthcare. Following completion of the survey, 11 of these participants agreed to further semi-structured interviews to explore this further in their own words. Interview conversations were transcribed, checked; together with the responses to open questions in the survey. The data were then analyzed thematically by members of the research team. We conducted framework analysis from a post-positivist perspective, using the Person-centered Practice Framework to explore participants' experiences. Results: There were few examples of people describing person-centered care. People experienced barriers to accessing support, and negative experiences of care that represented complexities enacting person-centered care at each level of the framework (processes, practice environment, prerequisites, and macro context). These barriers were influenced greatly by the pandemic, for example, with health professionals being harder to access. Some experiences related to the ways in which health professionals responded to the context, for example, positive examples included active listening, recognition of people's experiences, seeking to find out more, and engaging in collaborative problem-solving. Discussion: People want to feel heard, supported to navigate healthcare systems, source trustworthy information, find appropriate services, and collaborate in learning and problem-solving with healthcare professionals. There have been enormous challenges to the provision of healthcare throughout the pandemic. Moving forward is crucial with emphasis on overcoming barriers to person-centered healthcare. This should focus on steps now and also in planning for the possibility of further rapid changes in the demand for and provision of healthcare.}, } @article {pmid36188760, year = {2021}, author = {Uddin, T and Rahim, HR and Khandaker, MN}, title = {The Impact of COVID-19 and the Challenges of Post-COVID Rehabilitation in a Developing Country.}, journal = {Frontiers in rehabilitation sciences}, volume = {2}, number = {}, pages = {746061}, pmid = {36188760}, issn = {2673-6861}, abstract = {The coronavirus disease 2019 (COVID-19) and its impact on human functioning are gaining increased interest. Like many other lower-income countries, the Bangladesh health and rehabilitation sector was adversely affected by COVID-19. Multiple challenges were identified for preparedness and medical rehabilitation during COVID-19 surges. Appropriate supervision of multispecialty long COVID clinics and attention to rehabilitation teamwork are important. Rehabilitation plays a key role in the management of patients with COVID-19 and can reduce the length of hospital stay and improve health outcomes. While waiting for people to be fully vaccinated; ensuring equitable access to COVID-19 vaccination, health care, and rehabilitation services among people with disabilities should be a part of the core mission during the pandemic. All levels of care including, critical, post-acute, or long covid clinic scale-up of rehabilitation services are needed. A physiatrist-led rehabilitation team approach is vital for the adaptation of rehabilitation interventions to improve the functional outcomes of persons with impairment and disability affected by COVID-19.}, } @article {pmid36188433, year = {2022}, author = {Zhang, H and Li, X and Huang, L and Gu, X and Wang, Y and Liu, M and Liu, Z and Zhang, X and Yu, Z and Wang, Y and Huang, C and Cao, B}, title = {Lung-function trajectories in COVID-19 survivors after discharge: A two-year longitudinal cohort study.}, journal = {EClinicalMedicine}, volume = {54}, number = {}, pages = {101668}, pmid = {36188433}, issn = {2589-5370}, abstract = {BACKGROUND: Data on the long-term trajectories of lung function are scarce in COVID-19 survivors.

METHODS: We re-analyzed the data from a prospective longitudinal cohort follow-up study of COVID-19 survivors over 2 years after infection. All participants were divided into scale 3, scale 4 and scale 5-6 groups according to seven-category ordinal scale. The changes of pulmonary function tests (PFTs), the Modified Medical Research Council (mMRC) Dyspnea Scale, 6-min walking test health-related quality of life (HRQoL) across the three serial follow-up visits were evaluated, and compared among three groups. We performed liner regression to determine potential factors that were associated with changes of PFTs and distance walked in 6 minutes (6MWD).

FINDINGS: In this study, 288 participants generally presented an improvement of PFTs parameters from 6 months to 1 year after infection. The scale 5-6 group displayed a significantly higher increase of PFTs compared with scale 3 and scale 4 groups (all p<0.0167), and corticosteroids therapy was identified as a protective factor for the PFTs improvement with a correlation coefficient of 2.730 (0.215-5.246) for forced vital capacity (FVC), 2.909 (0.383-5.436) for total lung capacity (TLC), and 3.299 (0.211-6.387) for diffusion capacity for carbon monoxide (DLco), respectively. From 1-year to 2-year follow-up, the PFTs parameters generally decreased, which was not observed to be associated with changes of 6MWD and HRQoL. Dyspnea (mMRC≥1) generally decreased over time (23.3% [61/262] for 6-month, 27.9% [67/240] for 1-year, 13.4% [35/261] for 2-year), and 6MWD increased continuously (500.0 m vs 505.0 m vs 525.0 m).

INTERPRETATION: Corticosteroids therapy during hospitalization was a protective factor for PFTs improvement from 6 months to 1 year. The relatively fast decline trend of PFTs from 1 year to 2 years needs to be paid attention and further validated in the future follow-up study.

FUNDINGS: This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-048) and the National Key Research and Development Program of China (2021YFC0864700).}, } @article {pmid36188407, year = {2022}, author = {Kelly, KM and Anghinah, R and Kullmann, A and Ashmore, RC and Synowiec, AS and Gibson, LC and Manfrinati, L and de Araújo, A and Spera, RR and Brucki, SMD and Tuma, RL and Braverman, A and Kiderman, A}, title = {Oculomotor, vestibular, reaction time, and cognitive tests as objective measures of neural deficits in patients post COVID-19 infection.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {919596}, pmid = {36188407}, issn = {1664-2295}, abstract = {OBJECTIVE: An alarming proportion (>30%) of patients affected by SARS-CoV-2 (COVID-19) continue to experience neurological symptoms, including headache, dizziness, smell and/or taste abnormalities, and impaired consciousness (brain fog), after recovery from the acute infection. These symptoms are self-reported and vary from patient to patient, making it difficult to accurately diagnose and initiate a proper treatment course. Objective measures to identify and quantify neural deficits underlying the symptom profiles are lacking. This study tested the hypothesis that oculomotor, vestibular, reaction time, and cognitive (OVRT-C) testing using eye-tracking can objectively identify and measure functional neural deficits post COVID-19 infection.

METHODS: Subjects diagnosed with COVID-19 (n = 77) were tested post-infection with a battery of 20 OVRT-C tests delivered on a portable eye-tracking device (Neurolign Dx100). Data from 14 tests were compared to previously collected normative data from subjects with similar demographics. Post-COVID subjects were also administered the Neurobehavioral Symptom Inventory (NSI) for symptom evaluation.

RESULTS: A significant percentage of post COVID-19 patients (up to 86%) scored outside the norms in 12 out of 14 tests, with smooth pursuit and optokinetic responses being most severely affected. A multivariate model constructed using stepwise logistic regression identified 6 metrics as significant indicators of post-COVID patients. The area under the receiver operating characteristic curve (AUC) was 0.89, the estimated specificity was 98% (with cutoff value of 0.5) and the sensitivity was 88%. There were moderate but significant correlations between NSI domain key variables and OVRT-C tests.

CONCLUSIONS: This study demonstrates the feasibility of OVRT-C testing to provide objective measures of neural deficits in people recovering from COVID-19 infection. Such testing may serve as an efficient tool for identifying hidden neurological deficits post COVID-19, screening patients at risk of developing long COVID, and may help guide rehabilitation and treatment strategies.}, } @article {pmid36187895, year = {2022}, author = {Lazova, S and Gerenska, D and Slabakova, Y and Velikova, T}, title = {Immunological features of the multisystem inflammatory syndrome associated with SARS-CoV-2 in children.}, journal = {American journal of clinical and experimental immunology}, volume = {11}, number = {4}, pages = {64-71}, pmid = {36187895}, issn = {2164-7712}, abstract = {A particular group of children developed severe multisystem inflammation associated with current or recent SARS-CoV-2 infection or contact with a COVID-19 patient in the previous few weeks. The condition was defined as multisystem inflammatory syndrome (MIS) in children (MIS-C). As the definition of CDC and WHO is fast widely accepted, the lack of an international consensus on the definition of the syndrome cases, however, leads to some difficulties for clinicians. Additionally, MIS-C shares some immunological, pathological features with the conditions, such as cytokine storm, long COVID and/or post-COVID syndrome. The picture is further complicated by the existence of the syndrome in adults (MIS-A). Therefore, we have compared these conditions from the immunological point of view in our review based on the published case reports, studies, systematic reviews and metaanalyses. This knowledge is essential not only for immunologists. The paediatricians must be familiar with the immunological bases of the syndrome and implement it in on-time recognition and diagnosis and minimize systemic damage of this life-threatening condition at the earliest stage possible. Further investigations still need to be done to find and develop the best effective therapy and prophylactics.}, } @article {pmid36187720, year = {2022}, author = {Green, R and Mayilsamy, K and McGill, AR and Martinez, TE and Chandran, B and Blair, LJ and Bickford, PC and Mohapatra, SS and Mohapatra, S}, title = {SARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.}, journal = {Molecular therapy. Methods & clinical development}, volume = {27}, number = {}, pages = {217-229}, pmid = {36187720}, issn = {2329-0501}, support = {I01 BX004626/BX/BLRD VA/United States ; IK6 BX004214/BX/BLRD VA/United States ; IK6 BX004212/BX/BLRD VA/United States ; R01 NS073899/NS/NINDS NIH HHS/United States ; I01 BX005490/BX/BLRD VA/United States ; R01 CA180758/CA/NCI NIH HHS/United States ; I01 BX005757/BX/BLRD VA/United States ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has caused over 600,000,000 infections globally thus far. Up to 30% of individuals with mild to severe disease develop long COVID, exhibiting diverse neurologic symptoms including dementias. However, there is a paucity of knowledge of molecular brain markers and whether these can precipitate the onset of Alzheimer's disease (AD). Herein, we report the brain gene expression profiles of severe COVID-19 patients showing increased expression of innate immune response genes and genes implicated in AD pathogenesis. The use of a mouse-adapted strain of SARS-CoV-2 (MA10) in an aged mouse model shows evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferon-inducible gene Ifi204, and complement genes C4 and C5AR1. Brain histopathology shows AD signatures including increased tau-phosphorylation, tau-oligomerization, and α-synuclein expression in aged MA10 infected mice. The results of gene expression profiling of SARS-CoV-2-infected and AD brains and studies in the MA10 aged mouse model taken together, for the first time provide evidence suggesting that SARS-CoV-2 infection alters expression of genes in the brain associated with the development of AD. Future studies of common molecular markers in SARS-CoV-2 infection and AD could be useful for developing novel therapies targeting AD.}, } @article {pmid36187294, year = {2022}, author = {Méndez-García, LA and Escobedo, G and Minguer-Uribe, AG and Viurcos-Sanabria, R and Aguayo-Guerrero, JA and Carrillo-Ruiz, JD and Solleiro-Villavicencio, H}, title = {Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations.}, journal = {Frontiers in cellular neuroscience}, volume = {16}, number = {}, pages = {977039}, pmid = {36187294}, issn = {1662-5102}, abstract = {SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.}, } @article {pmid36186977, year = {2022}, author = {Schieffer, E and Schieffer, B}, title = {The rationale for the treatment of long-Covid symptoms - A cardiologist's view.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {992686}, pmid = {36186977}, issn = {2297-055X}, abstract = {The ongoing coronavirus disease 2019 pandemic left us with thousands of patients suffering from neurological, cardiovascular, and psychiatric disorders named post-acute sequelae of COVID-19 or just long-Covid. In parallel, the vaccination campaigns against SARS-CoV-2 spike protein saved millions of lives worldwide but long-Covid symptoms also appeared rarely following vaccination with a strong overlap to the "canonical" long-Covid symptoms. A therapeutic strategy targeting both, post-VAC and post-SARS-CoV-2 long-Covid symptoms is warranted since exposure to the S-protein either by vaccination or SARS-CoV-2 infection may trigger identical immuno-inflammatory cascades resulting in long-Covid symptoms.}, } @article {pmid36186771, year = {2022}, author = {Goldman, M}, title = {Long Covid, a great imitator of the 21th century.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1026425}, pmid = {36186771}, issn = {2296-858X}, } @article {pmid36186173, year = {2022}, author = {Tsioutis, C and Tofarides, A and Spernovasilis, N}, title = {Transition beyond the acute phase of the COVID-19 pandemic: Need to address the long-term health impacts of COVID-19.}, journal = {World journal of clinical cases}, volume = {10}, number = {27}, pages = {9967-9969}, pmid = {36186173}, issn = {2307-8960}, abstract = {Despite gaps in knowledge, long-term sequelae of coronavirus disease 2019 (COVID-19) infections are globally acknowledged and thus require special attention by public health organizations and services. Therefore, it is necessary to support and promote public health initiatives that address long-term disability due to COVID-19.}, } @article {pmid36184207, year = {2022}, author = {Galluzzo, V and Zazzara, MB and Ciciarello, F and Savera, G and Pais, C and Calvani, R and Picca, A and Marzetti, E and Landi, F and Tosato, M and , }, title = {Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function.}, journal = {Clinical nutrition ESPEN}, volume = {51}, number = {}, pages = {215-221}, pmid = {36184207}, issn = {2405-4577}, mesh = {Aged ; Amino Acids ; *COVID-19 ; Dietary Supplements ; Fatigue ; Female ; Ferritins ; *Hand Strength ; Humans ; Middle Aged ; Muscle Strength/physiology ; Plant Extracts ; Survivors ; Vitamins ; }, abstract = {BACKGROUND: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.

AIM: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vitamins, and plant extracts (Apportal®) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.

METHODS: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal® for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one-minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS).

RESULTS: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low-flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at t1 as compared to t0. A trend, although not significant, in reduction of ferritin levels was found after nutritional supplementation (94.4 vs. 84.3, respectively; p = 0.01). The self-rated health status increased by at least 13 points (t0, mean 57.6 ± 5.86; t1, mean 71.4 ± 6.73; p < 0.05).

CONCLUSIONS: After 28 days of nutritional supplementation with Apportal® in COVID-19 survivors affected by fatigue with reduced tolerance to exercise, we found a significant improvement in means of muscle strength and physical performance, associated with enhancement of self-rated health status between t0 and t1.}, } @article {pmid36184010, year = {2022}, author = {Ku, CH and Yong, SB and Wei, JC}, title = {Letter to the Editor: Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN survey.}, journal = {Pharmacological research}, volume = {185}, number = {}, pages = {106478}, pmid = {36184010}, issn = {1096-1186}, mesh = {Humans ; Ascorbic Acid/therapeutic use ; Vitamins ; Arginine/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, } @article {pmid36182048, year = {2022}, author = {Yavropoulou, MP and Tsokos, GC and Chrousos, GP and Sfikakis, PP}, title = {Protracted stress-induced hypocortisolemia may account for the clinical and immune manifestations of Long COVID.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {245}, number = {}, pages = {109133}, pmid = {36182048}, issn = {1521-7035}, mesh = {Humans ; Pituitary-Adrenal System/physiology ; Hypothalamo-Hypophyseal System/physiology ; *COVID-19/complications ; Hydrocortisone ; *Fatigue Syndrome, Chronic/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {About one out of eight people to convalesce from COVID-19 suffer from the so called Long COVID, a syndrome of non-specific symptoms with unclear pathogenesis. In a recent study published in Cell Long COVID participants reporting respiratory symptoms had low cortisol levels. In an as yet unpublished analysis from Yale University low plasma cortisol levels discriminated Long COVID from asymptomatic convalescent or healthy non-infected controls. Although various immune perturbations were present in Long COVID, low levels of cortisol were prominent and strikingly, depression and anxiety were increased. It has become clear that Long COVID features may be similar to those described in myalgic encephalomyelitis/chronic fatigue syndrome, post-SARS sickness syndrome, and various chronic stress syndromes which have been linked to hypocortisolemia. Notably, lack of response of the hypothalamic-pituitary-adrenal axis to hypocortisolemia shows a suppressed axis in Long COVID. We suggest that the inability of hypothalamic-pituitary-adrenal axis to recover after the acute illness, perhaps due to protracted stress in predisposed individuals, may represent the pathogenetic basis of the Long COVID-associated clinical and immunological manifestations.}, } @article {pmid36178611, year = {2022}, author = {DePace, NL and Colombo, J}, title = {Long-COVID Syndrome and the Cardiovascular System: A Review of Neurocardiologic Effects on Multiple Systems.}, journal = {Current cardiology reports}, volume = {24}, number = {11}, pages = {1711-1726}, pmid = {36178611}, issn = {1534-3170}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; SARS-CoV-2 ; *Cardiovascular System ; }, abstract = {PURPOSE OF REVIEW: Long-COVID syndrome is a multi-organ disorder that persists beyond 12 weeks post-acute SARS-CoV-2 infection (COVID-19). Here, we provide a definition for this syndrome and discuss neuro-cardiology involvement due to the effects of (1) angiotensin-converting enzyme 2 receptors (the entry points for the virus), (2) inflammation, and (3) oxidative stress (the resultant effects of the virus).

RECENT FINDINGS: These effects may produce a spectrum of cardio-neuro effects (e.g., myocardial injury, primary arrhythmia, and cardiac symptoms due to autonomic dysfunction) which may affect all systems of the body. We discuss the symptoms and suggest therapies that target the underlying autonomic dysfunction to relieve the symptoms rather than merely treating symptoms. In addition to treating the autonomic dysfunction, the therapy also treats chronic inflammation and oxidative stress. Together with a full noninvasive cardiac workup, a full assessment of the autonomic nervous system, specifying parasympathetic and sympathetic (P&S) activity, both at rest and in response to challenges, is recommended. Cardiac symptoms must be treated directly. Cardiac treatment is often facilitated by treating the P&S dysfunction. Cardiac symptoms of dyspnea, chest pain, and palpitations, for example, need to be assessed objectively to differentiate cardiac from neural (autonomic) etiology. Long-term myocardial injury commonly involves P&S dysfunction. P&S assessment usually connects symptoms of Long-COVID to the documented autonomic dysfunction(s).}, } @article {pmid36176520, year = {2022}, author = {Schrimpf, A and Braesigk, A and Lippmann, S and Bleckwenn, M}, title = {Management and treatment of long COVID symptoms in general practices: An online-based survey.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {937100}, pmid = {36176520}, issn = {2296-2565}, mesh = {*COVID-19/complications/therapy ; Fatigue ; *General Practice ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Independent from initial severity, many patients develop persistent symptoms after infection with SARS-CoV-2, described as long COVID syndrome. Most of these patients are treated by general practitioners (GPs). As evidence-based treatment recommendations are still sparse, GPs must make their therapy decisions under uncertainty. We investigated (1) the most frequently observed long COVID symptoms in general practices and (2) GPs' applied treatment and rehabilitation plans for these symptoms. In total, 143 German GPs participated in an online-based survey between 05/2021 and 07/2021. We found that each GP practice was treating on average 12 patients with long COVID symptoms. Most frequently seen symptoms were fatigue and reduced performance. Current therapy options were rated as poor and loss of smell and taste, fatigue, or lack of concentration were perceived to be especially difficult to treat. The use of drug and non-drug therapies and specialist referrals focused primarily on physiological and less on psychosomatic/psychological rehabilitation and followed guidelines of similar conditions. Our results provide first insights into how GPs approach a newly emerging condition in the absence of guidelines, evidence-based recommendations, or approved therapies, and might inform about GP preparedness in future pandemics. Our results also emphasize a gap between the current knowledge of the long COVID manifestation and knowledge about effective rehabilitation.}, } @article {pmid36175088, year = {2022}, author = {Hawke, LD and Brown, EE and Rodak, T and Rossell, S and Ski, CF and Strudwick, G and Thompson, DR and Wang, W and Xu, D and Castle, D}, title = {Protocol for a systematic review of interventions targeting mental health, cognition or psychological well-being among individuals with long COVID.}, journal = {BMJ open}, volume = {12}, number = {9}, pages = {e063846}, pmid = {36175088}, issn = {2044-6055}, mesh = {*COVID-19/complications ; Cognition ; Humans ; Knowledge ; *Mental Health ; Meta-Analysis as Topic ; Systematic Reviews as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: For some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or 'long COVID', negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID.

METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A health sciences librarian will identify the relevant literature through comprehensive systematic searches of Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, medRxiv, PsyArXiv, China National Knowledge Internet and WANFANG Data databases, as well as The Cochrane Central Register of Controlled Trials, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Studies will be selected through a title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data extracted will include intervention descriptions and efficacy metrics. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted. Risk of bias assessment will be conducted using the Cochrane Risk of Bias 2.0 tool.

ETHICS AND DISSEMINATION: Ethical approval for systematic reviews is not required. As researchers and clinicians respond to the new clinical entity that long COVID represents, this review will synthesise a rapidly emerging evidence base describing and testing interventions to promote mental health, cognition or psychological well-being. Results will therefore be disseminated through an open-access peer-reviewed publication and conference presentations to inform research and clinical practice.

PROSPERO REGISTRATION NUMBER: CRD42022318678.}, } @article {pmid36172860, year = {2022}, author = {Monroy-Iglesias, MJ and Tremble, K and Russell, B and Moss, C and Dolly, S and Sita-Lumsden, A and Cortellini, A and Pinato, DJ and Rigg, A and Karagiannis, SN and Van Hemelrijck, M}, title = {Long-term effects of COVID-19 on cancer patients: the experience from Guy's Cancer Centre.}, journal = {Future oncology (London, England)}, volume = {18}, number = {32}, pages = {3585-3594}, doi = {10.2217/fon-2022-0088}, pmid = {36172860}, issn = {1744-8301}, support = {MR/L023091/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; COVID-19 Testing ; *COVID-19/complications/epidemiology ; *Neoplasms/complications/epidemiology ; Dyspnea ; }, abstract = {Background: Few studies have investigated the long-term effects of COVID-19 on cancer patients. Materials & methods: The authors conducted a telephone survey on the long-term symptoms of cancer patients from Guy's Cancer Centre. They compared patients whose symptoms occurred/got worse over 4 weeks after COVID-19 diagnosis (classified as long COVID) with patients who did not develop symptoms or whose symptoms occurred/got worse in the first 4 weeks after diagnosis. Results: The authors analyzed responses from 80 patients with a previous COVID-19 diagnosis; 51.3% (n = 41) developed long COVID. The most common symptoms were fatigue, breathlessness and cognitive impairment. Conclusion: Findings suggest that over half of the cancer population will experience long-term effects after their initial COVID-19 diagnosis. Further studies are required to validate the findings of this study.}, } @article {pmid36172134, year = {2022}, author = {O'Connor, EE and Rednam, N and O'Brien, R and O'Brien, S and Rock, P and Levine, A and Zeffiro, TA}, title = {Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.09.22.22280222}, pmid = {36172134}, abstract = {BACKGROUND: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups.

METHODS: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention.

RESULTS: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests.

CONCLUSION: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.}, } @article {pmid36171050, year = {2022}, author = {Lloyd-Evans, PHI and Baldwin, MM and Daynes, E and Hong, A and Mills, G and Goddard, ACN and Chaplin, E and Gardiner, N and Singh, SJ and , }, title = {Early experiences of the Your COVID Recovery[®] digital programme for individuals with long COVID.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {36171050}, issn = {2052-4439}, mesh = {*COVID-19/complications ; Comorbidity ; Female ; Humans ; Male ; *Quality of Life ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To describe the early data from the Your COVID Recovery[®] digital programme and to explore the data collected from two embedded outcome measures.

DESIGN: Observational.

SETTING: Primary and secondary care (England-Online).

PARTICIPANTS: 110 individuals completed the programme (68.1% female, 88.1% White British, age: 46.3 (10.8) years, weight: 86.5 (21.1) kg, height: 169.3 (10.0) cm). 47.2% of patients reported comorbidities.

INTERVENTION: Following an assessment by a healthcare professional, individuals with long COVID were offered access to the Your COVID Recovery[®] digital programme. The programme comprises of four stages for the participants to progress through. Participants are encouraged to record severity of their symptoms and amount of activity they are doing on a symptom and an activity tracker. Resources and interactive material on managing symptoms of long COVID are available throughout each stage.

PRIMARY OUTCOME MEASURES: Questionnaire (EuroQ0l 5-Dimension 5-Level (EQ-5D-5L) and the chronic obstructive pulmonary disease assessment test (CAT)) data were extracted from the site from 11 March 2021 until 9 November 2021.

RESULTS: Participants were on the programme for 8.6 (4.3) weeks. There was a statistically significant increase in EQ-5D-5L visual analogue scale (VAS) score (pre=48.8 (19.5); post=59.9 (22.1); p<0.01). The EQ-5D-5L Index Value preintervention to postintervention did improve but not significantly (pre=0.5 (0.3); post=0.6 (0.3); p=0.09). CAT total score improved significantly preintervention to postintervention (pre=19.8 (7.2); post=15.6 (7.6); p<0.01). All CAT item scores significantly improved preintervention to postintervention (p<0.005), except the phlegm item score (p=0.168).

DISCUSSION: This early data describes the impact of the Your COVID Recovery[®] digital programme on the first cohort of patients to complete the digital recovery programme. The outcome data are promising and should encourage uptake.}, } @article {pmid36170723, year = {2022}, author = {Kozina, T and Gonda, X and Thibaut, F and Tavormina, G and Borisova, N and Gorbatchev, D and Protasov, A and Kolsanov, A and Smirnova, D}, title = {Educational Initiative about the COVID-19 Pandemic-Related Neuropsychiatry for Early Career Professionals in EU: The Impact of the Novel Virus on Brain, Mind, and Society.}, journal = {Psychiatria Danubina}, volume = {34}, number = {Suppl 8}, pages = {164-169}, pmid = {36170723}, issn = {0353-5053}, mesh = {Brain ; *COVID-19/complications ; Communicable Disease Control ; Humans ; *Neuropsychiatry ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic brought challenges to governments, healthcare systems (including, mental healthcare services), clinicians and researchers in the EU and worldwide. A range of neurological (e.g., brain fog, encephalitis, myalgia) and psychiatric (e.g., affective disorders, delirium, cognitive disturbances) complications of a novel nature have been observed in patients during the acute phase of illness, which often persist as a Long-COVID state for months after the primary recovery. The pandemic has progressed to a psychodemic and syndemic, affecting communities with social distress, panic, fears, increased home violence, and protest movements that derive from conspiracy theories and hostile attitudes towards vaccination and lockdown measures. In response to this complex scenario of major social changes, universities must face the need to equip the new generation of doctors with novel special skills.

SUBJECTS AND METHODS: The study course (50 hours duration; 20 lectures, three webinars, three e-discussion forums, five local seminars, two social events, three intermediate assessments and a final test for certification; bilingual Russian/English hybrid format, information materials, video-content, interactive web-page and social media) was developed by the team of the International Centre for Education and Research in Neuropsychiatry (ICERN), and is unique for the EU. The course integrates the most relevant data on SARS-Cov-2-related neuropsychiatry, and COVID-19' pandemic impact on mental health and society, including assignment of the vulnerable groups of students and healthcare professionals. The major topics covered during the course are (i) Novel virus, (ii) Brain, (iii) Society. The project takes place originally in Samara State Medical University. The ICERN Faculty includes academic staff from France, Hungary, Italy, Russia, Switzerland, invited speakers from the WHO Regional Office for Europe and World Psychiatric Association (EU Zones) members, some of them employed at ICERN by remote work contracts. The format of the educational process for students is hybrid suggesting both remote and face-to-face events. Distant learning participants and EU lecturers are to attend on-line via zoom platform, whereas local participants and staff work face-to-face in the ICERN video-conference room. The course is addressed to a broad audience of doctors, undergraduate and postgraduate students, and researchers from EU wishing to upgrade their knowledge in the pandemic-associated neuropsychiatry.

RESULTS: The evaluation process supposes three intermediate assessments and a final test for certification. On-line assessment is to be performed at the project web-page - 10 randomly selected questions with scoring from 1 to 10 each. The Pass Score is 70-100. At the end of the course all the participants receive certificates of Samara State Medical University according to the ERASMUS policy book, as planned in 2021.

CONCLUSIONS: We formatted this course as essential for the target audience to improve their resources of professional adaptability in the field of neuropsychiatry and mental healthcare management during challenging times. The ICERN course in pandemic-related neuropsychiatry is essential for early career health professionals and targets the principles of "academia without borders" in the context of international medical knowledge exchange. In the conditions of the changing social situation this educational content is necessary for the young doctors to acquire the add-on skills on flexibility to switch toward new professional approaches in the times of need. The long-term outcomes in pandemic-related neuropsychiatry are still to be seen, though the first feedback on the course content is already promising for the academic community.}, } @article {pmid36170709, year = {2022}, author = {Spurio, MG}, title = {Long-COVID and Stress Overload: A Direct Link with Psychophysical Disease. A Necessary Interconnection to Focalize Emerging Needs and Necessities.}, journal = {Psychiatria Danubina}, volume = {34}, number = {Suppl 8}, pages = {90-95}, pmid = {36170709}, issn = {0353-5053}, mesh = {Adaptation, Psychological ; Anxiety/epidemiology/etiology ; Anxiety Disorders ; *COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {The current world scenario of apprehension and suffering for the physical and economic health of people, has generated a situation of anxiety accompanied by an emotional overload of stress, often difficult to manage. The emerging Long-Covid syndrome has placed the emphasis on the persistence of clinical factors in some individuals, beyond the time which is normally considered acceptable for healing. This article aims to provide a contribution in the research of the possible causes related to the onset of Long-Covid syndrome, as well as in the understanding of the peculiar type of link between the various psycho-physical aspects and the health condition, while focusing attention on new ways of coping and treatment.}, } @article {pmid36170698, year = {2022}, author = {Vaiman, E and Gayduk, A and Strelnik, A and Smirnova, D and Davydkin, I and Fedyashov, I and Cumming, P and Shnayder, N and Nasyrova, R}, title = {Possible Clinical and Pharmacogenetic Predictors of the Efficacy and Safety of Carbamazepine in Post-COVID-19 Depression.}, journal = {Psychiatria Danubina}, volume = {34}, number = {Suppl 8}, pages = {31-37}, pmid = {36170698}, issn = {0353-5053}, mesh = {Anticonvulsants/adverse effects ; Antidepressive Agents/adverse effects ; Benzodiazepines ; *COVID-19/complications ; Carbamazepine/adverse effects ; Depression ; Humans ; Pharmacogenetics ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Individuals who have suffered from novel coronavirus disease (COVID-19) are at risk for developing post-COVID neuropsychiatric disorders, which are an integral part of the Long COVID syndrome. Depression and/or anxiety are considered the most common psychiatric disorders after experiencing COVID-19. Certain antiepileptic drugs, notably, carbamazepine (CMZ), are effective in the treatment of mood disorders, especially as mood stabilizers in bipolar affective disorder (BAD), but the efficacy of CMZ in Long COVID remains to be established. The aim of the review was to investigate pharmacogenetic predictors of safety and efficacy of CMZ in patients with depressive symptoms of Long COVID during the post-infection period.

SUBJECTS AND METHODS: We carried out a systematic search for publications in English and Russian on the safety and efficacy of CMZ in depressive disorders of different etiologies in the PubMed, Web of Science, Springer, Clinical Keys, Google Schooler, E-Library databases using keywords and combined word searches (carbamazepine, COVID-19, depression, epilepsy, post-COVID-syndrome) for the period from January 01,2020 to June 10, 2022.

RESULTS: We review the main adverse drug reactions (ADRs) associated with CMZ, drug-drug interactions, and genetic predictors of the development of ADR. Here, we consider as risk factors, candidate genes for CMZ metabolism, CMZ transport, immunohistocompatibility genes, and candidate genes for QT prolongation.

CONCLUSIONS: The choice of antidepressant treatment for patients with Long COVID is fraught because of the frequent occurrence of subclinical (interictal) epileptiform activity in the EEG. Consequently, antidepressant medications with a proconvulsant effect are contraindicated for Long COVID patients. CMZ may be a promising alternative for the treatment of depressive disorders in Long COVID states, given its mood-stabilizer, antidepressant, and antiepileptic profile.}, } @article {pmid36169757, year = {2022}, author = {Novak, P and Giannetti, MP and Weller, E and Hamilton, MJ and Mukerji, SS and Alabsi, HS and Systrom, D and Marciano, SP and Felsenstein, D and Mullally, WJ and Pilgrim, DM and Castells, M}, title = {Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {12}, pages = {6627-6638}, pmid = {36169757}, issn = {1590-3478}, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/complications ; Retrospective Studies ; *COVID-19/complications ; Autonomic Nervous System ; Heart Rate/physiology ; Blood Pressure/physiology ; *Small Fiber Neuropathy ; }, abstract = {BACKGROUND: The autonomic nervous system (ANS) is a complex network where sympathetic and parasympathetic domains interact inside and outside of the network. Correlation-based network analysis (NA) is a novel approach enabling the quantification of these interactions. The aim of this study is to assess the applicability of NA to assess relationships between autonomic, sensory, respiratory, cerebrovascular, and inflammatory markers on post-acute sequela of COVID-19 (PASC) and postural tachycardia syndrome (POTS).

METHODS: In this retrospective study, datasets from PASC (n = 15), POTS (n = 15), and matched controls (n = 11) were analyzed. Networks were constructed from surveys (autonomic and sensory), autonomic tests (deep breathing, Valsalva maneuver, tilt, and sudomotor test) results using heart rate, blood pressure, cerebral blood flow velocity (CBFv), capnography, skin biopsies for assessment of small fiber neuropathy (SFN), and various inflammatory markers. Networks were characterized by clusters and centrality metrics.

RESULTS: Standard analysis showed widespread abnormalities including reduced orthostatic CBFv in 100%/88% (PASC/POTS), SFN 77%/88%, mild-to-moderate dysautonomia 100%/100%, hypocapnia 87%/100%, and elevated inflammatory markers. NA showed different signatures for both disorders with centrality metrics of vascular and inflammatory variables playing prominent roles in differentiating PASC from POTS.

CONCLUSIONS: NA is suitable for a relationship analysis between autonomic and nonautonomic components. Our preliminary analyses indicate that NA can expand the value of autonomic testing and provide new insight into the functioning of the ANS and related systems in complex disease processes such as PASC and POTS.}, } @article {pmid36169708, year = {2023}, author = {Oikonomou, E and Lampsas, S and Theofilis, P and Souvaliotis, N and Papamikroulis, GA and Katsarou, O and Kalogeras, K and Pantelidis, P and Papaioannou, TG and Tsatsaragkou, A and Marinos, G and Siasos, G and Tousoulis, D and Vavuranakis, M}, title = {Impaired left ventricular deformation and ventricular-arterial coupling in post-COVID-19: association with autonomic dysregulation.}, journal = {Heart and vessels}, volume = {38}, number = {3}, pages = {381-393}, pmid = {36169708}, issn = {1615-2573}, mesh = {Humans ; Pulse Wave Analysis ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; Ventricular Function, Left/physiology ; *Ventricular Dysfunction, Left/diagnosis/etiology ; *Vascular Stiffness/physiology ; }, abstract = {Coronavirus disease-19 (COVID-19) has extended implications namely the long COVID-19 syndrome. We assessed over-time changes in left ventricular (LV) function, aortic stiffness, autonomic function, and ventricular-arterial coupling (VAC) in post-COVID-19 patients. We followed 34 post-COVID-19 subjects, up to 6 months post-hospital discharge. Subjects without COVID-19 served as control. We evaluated LV global longitudinal strain (LV-GLS), arterial stiffness [carotid-femoral pulse wave velocity (cf-PWV)], and heart rate variability -standard deviation of normal RR intervals (SDNN). VAC was estimated as the ratio of cf-PWV to LV-GLS. Post-COVID-19 individuals (1-month post-hospital discharge) presented with impaired LV-GLS [-18.4%(3.1) vs. -22.0%(2.7), P < 0.001], cf-PWV [12.1 m/s (3.2) vs. 9.6 m/s (1.9), P < 0.001], SDNN [111.3 ms (22.6) vs. 147.2 ms (14.0), P < 0.001], and VAC [-0.68 (0.22) vs. -0.44 (0.10), P < 0.001] compared to control. LV-GLS, SDNN, and VAC improved at the 6-month follow-up however they did not reach control levels. In post-COVID-19 subjects, SDNN and VAC were correlated at the 1-month (R = 0.499, P = 0.003) and 6-month (R = 0.372, P = 0.04) follow-up. Long COVID-19 syndrome was associated with impaired LV-GLS, SDNN, and VAC. Post-COVID-19 subjects presented with autonomic dysregulation associated with aortic stiffness, ventricular-arterial impairment, and LV dysfunction, even 6-months post-hospital discharge. These abnormalities may be related to the presence of long COVID-19 syndrome.}, } @article {pmid36168555, year = {2022}, author = {Ayoubkhani, D and Bosworth, ML and King, S and Pouwels, KB and Glickman, M and Nafilyan, V and Zaccardi, F and Khunti, K and Alwan, NA and Walker, AS}, title = {Risk of Long COVID in People Infected With Severe Acute Respiratory Syndrome Coronavirus 2 After 2 Doses of a Coronavirus Disease 2019 Vaccine: Community-Based, Matched Cohort Study.}, journal = {Open forum infectious diseases}, volume = {9}, number = {9}, pages = {ofac464}, pmid = {36168555}, issn = {2328-8957}, abstract = {We investigated long COVID incidence by vaccination status in a random sample of UK adults from April 2020 to November 2021. Persistent symptoms were reported by 9.5% of 3090 breakthrough severe acute respiratory syndrome coronavirus 2 infections and 14.6% of unvaccinated controls (adjusted odds ratio, 0.59 [95% confidence interval, .50-.69]), emphasizing the need for public health initiatives to increase population-level vaccine uptake.}, } @article {pmid36168319, year = {2022}, author = {Annam, P and Manda, A and Myneni, UK and Sahar, AN and Prasad, N and Sam, KK and Sahu, S and Reddy, KK}, title = {Corticosteroids induced avascular necrosis of hip, a "long COVID-19" complication: Case report.}, journal = {Annals of medicine and surgery (2012)}, volume = {82}, number = {}, pages = {104753}, pmid = {36168319}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Since it first surfaced, the new Coronavirus has multiplied and mutated into different forms, leading to a significant impact on people's lives. COVID-19's long-term impact is not completely known; It can only be hypothesized based on the prior outbreak of severe acute respiratory syndrome (SARS). Avascular necrosis (AVN) is one of these consequences, which if left untreated can lead to catastrophic events and bone collapse. It's important to remember that individuals who have recovered from COVID-19 infection are still at risk of developing AVN. The pathological findings in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are very similar to those seen in severe acute respiratory syndrome coronavirus (SARS-CoV) infection.

CASE PRESENTATION: We present cases of 27 and 69-year-old men with no comorbidities admitted with complaints of bilateral hip pain post covid treatment with corticosteroids and antivirals. The diagnosis was established based on history, physical examination, and magnetic resonance imaging (MRI).

CLINICAL DISCUSSION: The use of corticosteroids in the treatment of SARS-CoV-2 infection has saved many lives, and it is still advised for moderate to severe cases on a short-term basis. The long-term use of corticosteroids is associated with numerous side effects. One of the most prevalent side effects of steroids is avascular necrosis of the femoral head, which is aggravated by the disease process.

CONCLUSION: Early detection of Avascular necrosis is very crucial in its management due to its high progression rate. Low therapeutic doses of corticosteroids with minimal effective duration remain the key to halting its occurrence.}, } @article {pmid36166652, year = {2022}, author = {Harding, JL and Patel, SA and Davis, T and Patzer, RE and McDonald, B and Walker-Williams, D and Jagannathan, R and Teunis, L and Gander, J}, title = {Understanding Racial Disparities in COVID-19-Related Complications: Protocol for a Mixed Methods Study.}, journal = {JMIR research protocols}, volume = {11}, number = {10}, pages = {e38914}, pmid = {36166652}, issn = {1929-0748}, abstract = {BACKGROUND: In the United States, the COVID-19 pandemic has magnified the disproportionate and long-standing health disparities experienced by Black communities. Although it is acknowledged that social determinants of health (SDOH) rather than biological factors likely contribute to this disparity, few studies using rigorous analytic approaches in large, information-rich community-based data sets are dedicated to understanding the underlying drivers of these racial disparities.

OBJECTIVE: The overall aim of our study is to elucidate the mechanisms by which racial disparities in severe COVID-19 outcomes arise, using both quantitative and qualitative methods.

METHODS: In this protocol, we outline a convergent parallel mixed methods approach to identifying, quantifying, and contextualizing factors that contribute to the dramatic disparity in COVID-19 severity (ie, hospitalization, mortality) in Black versus white COVID-19 patients within the integrated health care system of Kaiser Permanente Georgia (KPGA). Toward this end, we will generate two quantitative cohorts of KPGA members with a confirmed COVID-19 diagnosis between January 1, 2020, and September 30, 2021: (1) an electronic medical record (EMR) cohort including routinely captured data on diagnoses, medications, and laboratory values, and a subset of patients hospitalized at Emory Healthcare to capture additional in-hospital data; and (2) a survey cohort, where participants will answer a range of questions related to demographics (eg, race, education), usual health behaviors (eg, physical activity, smoking), impact of COVID-19 (eg, job loss, caregiving responsibilities), and medical mistrust. Key outcomes of interest for these two cohorts include hospitalization, mortality, intensive care unit admission, hospital readmission, and long COVID-19. Finally, we will conduct qualitative semistructured interviews to capture perceptions of and experiences of being hospitalized with COVID-19 as well as related interactions with KPGA health care providers. We will analyze and interpret the quantitative and qualitative data separately, and then integrate the qualitative and quantitative findings using a triangulation design approach.

RESULTS: This study has been funded by a Woodruff Health Sciences grant from December 2020 to December 2022. As of August 31, 2022, 31,500 KPGA members diagnosed with COVID-19 have been included in the EMR cohort, including 3028 who were hospitalized at Emory Healthcare, and 482 KPGA members completed the survey. In addition, 20 KPGA members (10 Black and 10 white) have been interviewed about their experiences navigating care with COVID-19. Quantitative and qualitative data cleaning and coding have been completed. Data analysis is underway with results anticipated to be published in December 2022.

CONCLUSIONS: Results from this mixed methods pilot study in a diverse integrated care setting in the southeastern United States will provide insights into the mechanisms underpinning racial disparities in COVID-19 complications. The quantitative and qualitative data will provide important context to generate hypotheses around the mechanisms for racial disparities in COVID-19, and may help to inform the development of multilevel strategies to reduce the burden of racial disparities in COVID-19 and its ongoing sequelae. Incorporating contextual information, elucidated from qualitative interviews, will increase the efficacy, adoption, and sustainability of such strategies.

RR1-10.2196/38914.}, } @article {pmid36166651, year = {2022}, author = {Wright, H and Turner, A and Ennis, S and Percy, C and Loftus, G and Clyne, W and Matouskova, G and Martin, F}, title = {Digital Peer-Supported Self-Management Intervention Codesigned by People With Long COVID: Mixed Methods Proof-of-Concept Study.}, journal = {JMIR formative research}, volume = {6}, number = {10}, pages = {e41410}, pmid = {36166651}, issn = {2561-326X}, abstract = {BACKGROUND: There are around 1.3 million people in the United Kingdom with the devastating psychological, physical, and cognitive consequences of long COVID (LC). UK guidelines recommend that LC symptoms be managed pragmatically with holistic support for patients' biopsychosocial needs, including psychological, emotional, and physical health. Self-management strategies, such as pacing, prioritization, and goal setting, are vital for the self-management of many LC symptoms.

OBJECTIVE: This paper describes the codevelopment and initial testing of a digital intervention combining peer support with positive psychology approaches for self-managing the physical, emotional, psychological, and cognitive challenges associated with LC. The objectives of this study were to (1) codesign an intervention with and for people with LC; (2) test the intervention and study methods; (3) measure changes in participant well-being, self-efficacy, fatigue, and loneliness; and (4) understand the types of self-management goals and strategies used by people with LC.

METHODS: The study used a pre-post, mixed methods, pragmatic, uncontrolled design. Digital intervention content was codeveloped with a lived-experience group to meet the needs uncovered during the intervention development and logic mapping phase. The resulting 8-week digital intervention, Hope Programme for Long COVID, was attended by 47 participants, who completed pre- and postprogram measures of well-being, self-efficacy, fatigue, and loneliness. Goal-setting data were extracted from the digital platform at the end of the intervention.

RESULTS: The recruitment rate (n=47, 83.9%) and follow-up rate (n=28, 59.6%) were encouraging. Positive mental well-being (mean difference 6.5, P<.001) and self-efficacy (mean difference 1.1, P=.009) improved from baseline to postcourse. All goals set by participants mapped onto the 5 goal-oriented domains in the taxonomy of everyday self-management strategies (TEDSS). The most frequent type of goals was related to activity strategies, followed by health behavior and internal strategies.

CONCLUSIONS: The bespoke self-management intervention, Hope Programme for Long COVID, was well attended, and follow-up was encouraging. The sample characteristics largely mirrored those of the wider UK population with LC. Although not powered to detect statistically significant changes, the preliminary data show improvements in self-efficacy and positive mental well-being. Our next trial (ISRCTN: 11868601) will use a nonrandomized waitlist control design to further examine intervention efficacy.}, } @article {pmid36166648, year = {2022}, author = {Fuster-Casanovas, A and Fernandez-Luque, L and Nuñez-Benjumea, FJ and Moreno Conde, A and Luque-Romero, LG and Bilionis, I and Rubio Escudero, C and Chicchi Giglioli, IA and Vidal-Alaball, J}, title = {An Artificial Intelligence-Driven Digital Health Solution to Support Clinical Management of Patients With Long COVID-19: Protocol for a Prospective Multicenter Observational Study.}, journal = {JMIR research protocols}, volume = {11}, number = {10}, pages = {e37704}, pmid = {36166648}, issn = {1929-0748}, abstract = {BACKGROUND: COVID-19 pandemic has revealed the weaknesses of most health systems around the world, collapsing them and depleting their available health care resources. Fortunately, the development and enforcement of specific public health policies, such as vaccination, mask wearing, and social distancing, among others, has reduced the prevalence and complications associated with COVID-19 in its acute phase. However, the aftermath of the global pandemic has called for an efficient approach to manage patients with long COVID-19. This is a great opportunity to leverage on innovative digital health solutions to provide exhausted health care systems with the most cost-effective and efficient tools available to support the clinical management of this population. In this context, the SENSING-AI project is focused on the research toward the implementation of an artificial intelligence-driven digital health solution that supports both the adaptive self-management of people living with long COVID-19 and the health care staff in charge of the management and follow-up of this population.

OBJECTIVE: The objective of this protocol is the prospective collection of psychometric and biometric data from 10 patients for training algorithms and prediction models to complement the SENSING-AI cohort.

METHODS: Publicly available health and lifestyle data registries will be consulted and complemented with a retrospective cohort of anonymized data collected from clinical information of patients diagnosed with long COVID-19. Furthermore, a prospective patient-generated data set will be captured using wearable devices and validated patient-reported outcomes questionnaires to complement the retrospective cohort. Finally, the 'Findability, Accessibility, Interoperability, and Reuse' guiding principles for scientific data management and stewardship will be applied to the resulting data set to encourage the continuous process of discovery, evaluation, and reuse of information for the research community at large.

RESULTS: The SENSING-AI cohort is expected to be completed during 2022. It is expected that sufficient data will be obtained to generate artificial intelligence models based on behavior change and mental well-being techniques to improve patients' self-management, while providing useful and timely clinical decision support services to health care professionals based on risk stratification models and early detection of exacerbations.

CONCLUSIONS: SENSING-AI focuses on obtaining high-quality data of patients with long COVID-19 during their daily life. Supporting these patients is of paramount importance in the current pandemic situation, including supporting their health care professionals in a cost-effective and efficient management of long COVID-19.

TRIAL REGISTRATION: Clinicaltrials.gov NCT05204615; https://clinicaltrials.gov/ct2/show/NCT05204615.

DERR1-10.2196/37704.}, } @article {pmid36166227, year = {2022}, author = {Sorg, AL and Becht, S and Jank, M and Armann, J and von Both, U and Hufnagel, M and Lander, F and Liese, JG and Niehues, T and Verjans, E and Wetzke, M and Stojanov, S and Behrends, U and Drosten, C and Schroten, H and von Kries, R}, title = {Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany.}, journal = {JAMA network open}, volume = {5}, number = {9}, pages = {e2233454}, pmid = {36166227}, issn = {2574-3805}, mesh = {Adolescent ; *COVID-19/complications/epidemiology ; Child ; Communicable Disease Control ; Cross-Sectional Studies ; *Fatigue Syndrome, Chronic/epidemiology/psychology ; Female ; Germany/epidemiology ; Humans ; Immunoglobulin G ; Male ; Pandemics ; Quality of Life ; SARS-CoV-2 ; Seroepidemiologic Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.

OBJECTIVE: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.

This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.

EXPOSURES: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.

MAIN OUTCOMES AND MEASURES: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.

RESULTS: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.

CONCLUSIONS AND RELEVANCE: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.}, } @article {pmid36165028, year = {2022}, author = {Freedberg, DE and Chang, L}, title = {Gastrointestinal symptoms in COVID-19: the long and the short of it.}, journal = {Current opinion in gastroenterology}, volume = {38}, number = {6}, pages = {555-561}, doi = {10.1097/MOG.0000000000000876}, pmid = {36165028}, issn = {1531-7056}, support = {U54 DK123755/DK/NIDDK NIH HHS/United States ; OT2 OD024899/OD/NIH HHS/United States ; }, mesh = {*COVID-19/complications ; *Gastrointestinal Diseases/diagnosis/etiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: A large and growing number of patients have persistent gastrointestinal symptoms that they attribute to COVID-19. SARS-CoV-2, the virus that causes COVID-19, replicates within the gut and acute COVID-19 is associated with alteration of the gut microbiome. This article reviews recent observational data related to gastrointestinal symptoms in 'long COVID' and discusses pathophysiologic mechanisms that might explain persistent post-COVID gastrointestinal symptoms.

RECENT FINDINGS: Gastrointestinal symptoms are present in half of the patients with acute COVID-19, persist 6 months after COVID-19 in 10-25% of patients, and are rated as the most bothersome symptom in 11% of all patients. These symptoms include heartburn, constipation, diarrhoea and abdominal pain and decline in prevalence with the passage of time. Long COVID gastrointestinal symptoms are associated with mental health symptoms (anxiety and depression) that predate COVID-19 and also with mental health symptoms that are concurrent, after recovery from COVID-19. The cause of long COVID gastrointestinal symptoms is unknown and hypotheses include the SARS-CoV-2 virus itself, which infects the gastrointestinal tract; COVID-19, which can be accompanied by gut microbiome changes, a profound systemic inflammatory response and critical illness; and/or effects of pandemic stress on gastrointestinal function and symptom perception, which may be unrelated to either SARS-CoV-2 or to COVID-19.

SUMMARY: New, persistent gastrointestinal symptoms are commonly reported after recovery from COVID-19. The pathophysiology of these symptoms is unknown but likely to be multifactorial.}, } @article {pmid36164285, year = {2022}, author = {Senjam, SS and Balhara, YPS and Kumar, P and Nischal, N and Manna, S and Madan, K and Ahmed, NH and Gupta, N and Vashist, P and Guleria, R}, title = {A Comprehensive Assessment of Self-Reported Post COVID-19 Symptoms Among Beneficiaries of Hospital Employee Scheme at a Tertiary Healthcare Institution in Northern India.}, journal = {International journal of general medicine}, volume = {15}, number = {}, pages = {7355-7372}, pmid = {36164285}, issn = {1178-7074}, abstract = {PURPOSE: With millions of people being affected by COVID-19, people living with post COVID-19 clinical symptoms (PCS) are expected to rise further. The primary aim of the study was to comprehensively assess self-reported PCS and its associated risk factors among beneficiaries of Hospital Employee Scheme of a tertiary healthcare institution in Delhi.

PATIENTS AND METHODS: An online cross-sectional study was conducted using a semi-structured questionnaire developed by employing nominal group technique among individuals aged 18 years and above who were novel SARS-CoV-2 positive from January to April 2021. Participants were telephoned first, before sending the online survey link. Socio-demographic data, information on PCS along with potential risk factors, pre-existing morbidities, vaccination status, severity of acute illness and management were collected between June and July 2021. PCS was presented as relative frequency; Chi-Square test and odds ratio; adjusted values were used to rule out any association between PCS and predictors.

RESULTS: In total, 773 of 1801 eligible participants responded to the survey (completion rate 42.9%), with a median age of 34 years (IQR 27-44). Males accounted for 56.4% and PCS was present in 33.2%. The most prevalent symptoms were fatigue (79.3%), arthralgia (33.4%), myalgia (29.9%), hair loss (28.0%), headache (27.2%), breathlessness (25.3%), and sleep disturbance (25.3%). The prevalence of PCS was reduced to 12.8% at 12 weeks. Female gender, older age, oxygen supplementation, severity of acute illness, and pre-existing co-morbidities were positively associated with PCS. Vaccination (second dose) reduced the odds of developing PCS by 39% compared to unvaccinated participants (aOR 0.61; 95% CI 0.40-0.96).

CONCLUSION: PCS affects almost all organ systems of the body, regardless of the severity of acute COVID-19 illness. Two doses of vaccine hel reduce the development of PCS.}, } @article {pmid36163137, year = {2022}, author = {Alzueta, E and Perrin, PB and Yuksel, D and Ramos-Usuga, D and Kiss, O and Iacovides, S and de Zambotti, M and Cortes, M and Olabarrieta-Landa, L and Arango-Lasprilla, JC and Baker, FC}, title = {An international study of post-COVID sleep health.}, journal = {Sleep health}, volume = {8}, number = {6}, pages = {684-690}, pmid = {36163137}, issn = {2352-7226}, mesh = {Humans ; *COVID-19 ; COVID-19 Testing ; Quality of Life ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; Sleep ; *Sleep Initiation and Maintenance Disorders ; }, abstract = {OBJECTIVES: COVID-19 has infected millions of people worldwide, with growing evidence that individuals with a history of infection may continue to show persistent post-COVID symptoms (long COVID). The aim of this study was to investigate sleep health in an international sample of individuals who reported previously testing positive for COVID-19.

DESIGN: Cross-sectional.

SETTING: Online survey distributed online between March and June 2021.

PARTICIPANTS: A total of 1001 individuals who reported a positive diagnosis of COVID-19 across different geographical regions, including North and South America, Sub-Saharan Africa, and Europe.

MEASUREMENTS: Self-reported sleep health, using the Regulatory Satisfaction Alertness Timing Efficiency Duration scale, as recalled before a COVID-19 diagnosis and also reported currently.

RESULTS: Individuals reported worse overall current sleep health, with lower ratings across the 6 dimensions of sleep health (sleep regularity, satisfaction, alertness, timing, efficiency, and duration) compared to their ratings as recalled before COVID-19 infection. Greater severity of COVID-19 symptoms was the strongest predictor of poor current sleep health (P < .001), independent of demographics, presence of a pre-existing chronic health condition, and time since infection. Poor current sleep health was associated with poorer current quality of life (P < .001).

CONCLUSIONS: Poor current sleep health is evident in individuals with a history of COVID-19, particularly those with more severe symptoms at the time of their COVID-19 infection and is associated with a poorer quality of life. Clinicians and researchers should assess sleep health in COVID-19 patients and investigate long-term associations with their mental and physical health, as well as potential benefits of improving sleep in this population.}, } @article {pmid36161203, year = {2022}, author = {He, J and Yang, T}, title = {In the era of long COVID, can we seek new techniques for better rehabilitation?.}, journal = {Chronic diseases and translational medicine}, volume = {8}, number = {3}, pages = {149-153}, pmid = {36161203}, issn = {2589-0514}, } @article {pmid36160133, year = {2022}, author = {Carrasco-Garrido, P and Fernández-de-Las-Peñas, C and Hernández-Barrera, V and Palacios-Ceña, D and Jiménez-Trujillo, I and Gallardo-Pino, C}, title = {Benzodiazepines and Z-hypnotics consumption in long-COVID-19 patients: Gender differences and associated factors.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {975930}, pmid = {36160133}, issn = {2296-858X}, abstract = {BACKGROUND: Psychotropic drug consumption has increased during the COVID-19 pandemic. We describe here the prevalence and identifying factors associated with Benzodiazepine (BZD) and Z-hypnotics use among a sample of Spanish adults suffering from long-COVID-19 syndrome, from a gender perspective.

MATERIALS AND METHODS: Data were anonymously collected between 15th December 2021 and 15th March 2022. The collection form consisted of several questions gathering sociodemographic information, post-COVID symptom, health profile, and pharmacological drug intake. Using logistic multivariate regression models, we estimated the independent effect of each of these variables on self-medicated consumption. Three models were generated (female, male, and both gender).

RESULTS: Prevalence of BZD and Z-hypnotics use was 44.9% (46.5% for women; 37.8% for men). Zolpidem was the most consumed drug among male (20.7%), and lorazepam in female (31.1%). Patterns of drug consumption among female were related with number of post-COVID symptoms and smoking habit (AOR 2.76, 95%CI 1.16-6.52). Males under 40 years of age are more likely to consume BZD and Z-hypnotics (AOR 5.52, 95%CI 1.08-28.27).

CONCLUSION: The prevalence of consumption of BZD and Z-hypnotics in those subjects with long-COVID-19 in our study reaches values of 44.9%. Women with long-COVID-19 declare a higher prevalence of consumption than men. Predictors of BZD and Z-hypnotic in men were, age and number of medication use. Smoking habit and the number of post-COVID symptoms were predictive variables in women.}, } @article {pmid36159208, year = {2022}, author = {Duindam, HB and Kessels, RPC and van den Borst, B and Pickkers, P and Abdo, WF}, title = {Long-term cognitive performance and its relation to anti-inflammatory therapy in a cohort of survivors of severe COVID-19.}, journal = {Brain, behavior, & immunity - health}, volume = {25}, number = {}, pages = {100513}, pmid = {36159208}, issn = {2666-3546}, abstract = {BACKGROUND AND OBJECTIVES: Long-term cognitive performance data in former critically ill COVID-19 patients are sparse. Current evidence suggests that cognitive decline is related to neuroinflammation, which might be attenuated by COVID-19 related anti-inflammatory therapies. The objective of this prospective cohort study was to study long term cognitive outcomes following severe COVID-19 and the relation to anti-inflammatory therapies.

METHODS: Prospective observational cohort of patients that survived an intensive care unit (ICU) admission due to severe COVID-19. Six months after hospital discharge, we extensively assessed both objective cognitive functioning and subjective cognitive complaints. Furthermore, patients were stratified in cohorts according to their anti-inflammatory treatment (i.e. no immunomodulatory therapy, dexamethasone, or both dexamethasone and interleukin-6 receptor antagonist tocilizumab).

RESULTS: 96 patients were included (March 2020-June 2021, median [IQR] age 61 [55-69] years). 91% received invasive mechanical ventilation, and mean ± SD severity-of-disease APACHE-II-score at admission was 15.8 ± 4.1. After 6.5 ± 1.3 months, 27% of patients scored cognitively impaired. Patients that did or did not develop cognitive impairments were similar in ICU-admission parameters, clinical course and delirium incidence. Patients with subjective cognitive complaints (20%) were more likely women (61% vs 26%), and had a shorter ICU stay (median [IQR] 8 [5-15] vs 18 [9-31], p = 0.002). Objective cognitive dysfunction did not correlate with subjective cognitive dysfunction. 27% of the participants received dexamethasone during intensive care admission, 44% received additional tocilizumab and 29% received neither. Overall occurrence and severity of cognitive dysfunction were not affected by anti-inflammatory therapy, although patients treated with both dexamethasone and tocilizumab had worse executive functioning scores (Trail Making Test interference) than patients without anti-inflammatory treatment (T-score 40.3 ± 13.5 vs 49.1 ± 9.3, p = 0.007).

DISCUSSION: A relevant proportion of critically ill COVID-19 patients shows deficits in long-term cognitive functioning. Apart from more pronounced executive dysfunction, overall, anti-inflammatory therapy appeared not to affect long-term cognitive performance. Our findings provide insight in long-term cognitive outcomes in patients who survived COVID-19, that may facilitate health-care providers counseling patients and their caregivers.}, } @article {pmid36159093, year = {2022}, author = {Swarnakar, R and Yadav, SL}, title = {Rehabilitation in long COVID-19: A mini-review.}, journal = {World journal of methodology}, volume = {12}, number = {4}, pages = {235-245}, pmid = {36159093}, issn = {2222-0682}, abstract = {We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of 'new normal'. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.}, } @article {pmid36158335, year = {2022}, author = {Kalia, R and Kalia, R and Musih, J and Cubelo, M and Popat, J}, title = {Post-COVID-19 Syndrome: A Novel Diagnosis.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e28266}, pmid = {36158335}, issn = {2168-8184}, abstract = {Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.}, } @article {pmid36158308, year = {2022}, author = {Goldstein Ferber, S and Shoval, G and Zalsman, G and Weller, A}, title = {Does COVID-19 related symptomatology indicate a transdiagnostic neuropsychiatric disorder? - Multidisciplinary implications.}, journal = {World journal of psychiatry}, volume = {12}, number = {8}, pages = {1004-1015}, pmid = {36158308}, issn = {2220-3206}, abstract = {The clinical presentation that emerges from the extensive coronavirus disease 2019 (COVID-19) mental health literature suggests high correlations among many conventional psychiatric diagnoses. Arguments against the use of multiple comorbidities for a single patient have been published long before the pandemic. Concurrently, diagnostic recommendations for use of transdiagnostic considerations for improved treatment have been also published in recent years. In this review, we pose the question of whether a transdiagnostic mental health disease, including psychiatric and neuropsychiatric symptomology, has emerged since the onset of the pandemic. There are many attempts to identify a syndrome related to the pandemic, but none of the validated scales is able to capture the entire psychiatric and neuropsychiatric clinical presentation in infected and non-infected individuals. These scales also only marginally touch the issue of etiology and prevalence. We suggest a working hypothesis termed Complex Stress Reaction Syndrome (CSRS) representing a global psychiatric reaction to the pandemic situation in the general population (Type A) and a neuropsychiatric reaction in infected individuals (Type B) which relates to neurocognitive and psychiatric features which are part (excluding systemic and metabolic dysfunctions) of the syndrome termed in the literature as long COVID. We base our propositions on multidisciplinary scientific data regarding mental health during the global pandemic situation and the effects of viral infection reviewed from Google Scholar and PubMed between February 1, 2022 and March 10, 2022. Search in-clusion criteria were "mental health", "COVID-19" and "Long COVID", English language and human studies only. We suggest that this more comprehensive way of understanding COVID-19 complex mental health reactions may promote better prevention and treatment and serve to guide implementation of recommended administrative regulations that were recently published by the World Psychiatric Association. This review may serve as a call for an international investigation of our working hypothesis.}, } @article {pmid36156538, year = {2022}, author = {Zifko, UA and Yacob, M and Braun, BJ and Dietz, GPH}, title = {Alleviation of Post-COVID-19 Cognitive Deficits by Treatment with EGb 761®: A Case Series.}, journal = {The American journal of case reports}, volume = {23}, number = {}, pages = {e937094}, pmid = {36156538}, issn = {1941-5923}, mesh = {Adult ; Anti-Inflammatory Agents/therapeutic use ; *COVID-19/complications ; Cognition ; *Cognitive Dysfunction/drug therapy/etiology ; Endothelial Cells ; Fatigue ; Female ; Ginkgo biloba ; Humans ; Male ; Plant Extracts/pharmacology/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND Cognitive symptoms persisting longer than 3 months after infection, such as memory loss, or difficulties concentrating, have been reported in up to one-third of patients after COVID-19. Evidence-based therapeutic interventions to treat post-COVID-19 symptoms (also called "Long-COVID symptoms") have not yet been established, and the treating physicians must rely on conjecture to help patients. Based on its mechanism of action and its efficacy in treating cognitive impairment, as well as its good tolerability, the Ginkgo biloba special extract EGb 761 has been suggested as a remedy to alleviate cognitive post-COVID-19 symptoms. In many studies, EGb 761 has been demonstrated to protect endothelial cells, to have potent anti-inflammatory effects, and to enhance neuroplasticity. CASE REPORT Here, we report for the first time the application of EGb 761 in the therapy of post-COVID-19-related cognitive deficits. Three women and 2 men, aged 26 to 59 years (average age 34.6 years), presented with concentration and attention deficits, cognitive deficiencies, and/or fatigue 9-35 weeks after infection. A daily dose of 2×80 mg of EGb 761 did not cause any detectable adverse effects, and it substantially improved or completely restored cognitive deficits and, when initially present, also other symptoms, such as fatigue and hyposmia, within an observation period of up to 6 months. CONCLUSIONS Our observations support the hypothesis that EGb 761 might be a low-risk treatment option for post-COVID-19 patients with cognitive symptoms. Moreover, we derive recommendations for randomized controlled clinical trials to confirm efficacy in that indication.}, } @article {pmid36156274, year = {2022}, author = {Lund, EM and Ayers, KB}, title = {Ever-changing but always constant: "Waves" of disability discrimination during the COVID-19 pandemic in the United States.}, journal = {Disability and health journal}, volume = {15}, number = {4}, pages = {101374}, pmid = {36156274}, issn = {1876-7583}, mesh = {Humans ; United States/epidemiology ; *COVID-19 ; *Disabled Persons ; Pandemics ; Post-Acute COVID-19 Syndrome ; Social Discrimination ; }, abstract = {The ongoing novel coronavirus 2019 (COVID-19) pandemic has had considerable effects on the disability community. As the pandemic has progressed and changed, the manifestations of these effects have differed, and yet the underlying causes-ableism including the devaluation of disabled lives-have remained consistent. In this commentary, we explore the impact of the pandemic on the disability community in the United States, conceptualizing four distinct but overlapping "waves" of discrimination: 1) healthcare rationing and missed opportunities for disability inclusion, 2) access to resources, supplies, and accommodations; 3) vaccine access; and 4) long COVID and disability identity. Throughout our discussion of these waves, we detail the discrimination faced by people with disabilities, the underlying ableism that perpetuates it, and the resilience shown by the disability community. We end with a call for combating systemic ableism in healthcare and public health systems.}, } @article {pmid36155957, year = {2022}, author = {Haddad, A and Janda, A and Renk, H and Stich, M and Frieh, P and Kaier, K and Lohrmann, F and Nieters, A and Willems, A and Huzly, D and Dulovic, A and Schneiderhan-Marra, N and Jacobsen, EM and Fabricius, D and Zernickel, M and Stamminger, T and Bode, SFN and Himpel, T and Remppis, J and Engel, C and Peter, A and Ganzenmueller, T and Hoffmann, GF and Haase, B and Kräusslich, HG and Müller, B and Franz, AR and Debatin, KM and Tönshoff, B and Henneke, P and Elling, R}, title = {Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study.}, journal = {EBioMedicine}, volume = {84}, number = {}, pages = {104245}, pmid = {36155957}, issn = {2352-3964}, mesh = {Adolescent ; Adult ; *COVID-19/complications/epidemiology ; Child ; Female ; Humans ; Male ; Parents ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households.

METHODS: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires.

FINDINGS: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]).

INTERPRETATION: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful.

FUNDING: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.}, } @article {pmid36155767, year = {2022}, author = {Gallegos, M and Caycho-Rodríguez, T}, title = {[Long COVID-19: Clinical indicators].}, journal = {Revista medica de Chile}, volume = {150}, number = {4}, pages = {564-566}, doi = {10.4067/S0034-98872022000400564}, pmid = {36155767}, issn = {0717-6163}, mesh = {*COVID-19/complications/pathology/physiopathology ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36155748, year = {2022}, author = {Roy, R and McDonaugh, B and O'Gallagher, K}, title = {COVID-19 and the heart.}, journal = {British medical bulletin}, volume = {144}, number = {1}, pages = {4-11}, pmid = {36155748}, issn = {1471-8391}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Pandemics ; *Heart Failure/epidemiology/etiology ; }, abstract = {BACKGROUND: There is evidence for a bi-directional relationship between COVID-19 and the cardiovascular (CV) system.

SOURCE OF DATA: Published literature.

AREAS OF AGREEMENT: Pre-existing heart failure (HF) increases the risk of mortality with COVID-19. CV complications are recognized, including increased rates of acute coronary syndromes, HF, arrhythmia and myocarditis. Drugs targeting the angiotensin system are safe and may provide prognostic benefit.

AREAS OF CONTROVERSY: Vaccination as a cause of myocarditis remains a key area of contention.

GROWING POINTS: As the pandemic progresses, we are gaining more data about the long-term effects of COVID-19 on the CV system: long COVID, and medium-to-long-term increases in CV risk.

Large-scale longitudinal studies will shed light on long-term CV outcomes with COVID-19. Furthermore, the differential effects of COVID-19 variants on the CV system must be investigated.}, } @article {pmid36154716, year = {2022}, author = {Huang, Y and Pinto, MD and Borelli, JL and Asgari Mehrabadi, M and Abrahim, HL and Dutt, N and Lambert, N and Nurmi, EL and Chakraborty, R and Rahmani, AM and Downs, CA}, title = {COVID Symptoms, Symptom Clusters, and Predictors for Becoming a Long-Hauler Looking for Clarity in the Haze of the Pandemic.}, journal = {Clinical nursing research}, volume = {31}, number = {8}, pages = {1390-1398}, pmid = {36154716}, issn = {1552-3799}, support = {UL1 TR001414/TR/NCATS NIH HHS/United States ; }, mesh = {Male ; Humans ; Female ; *Pandemics ; *COVID-19/epidemiology ; SARS-CoV-2 ; Syndrome ; Risk Factors ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC) is defined as persistent symptoms after apparent recovery from acute COVID-19 infection, also known as COVID-19 long-haul. We performed a retrospective review of electronic health records (EHR) from the University of California COvid Research Data Set (UC CORDS), a de-identified EHR of PCR-confirmed SARS-CoV-2-positive patients in California. The purposes were to (1) describe the prevalence of PASC, (2) describe COVID-19 symptoms and symptom clusters, and (3) identify risk factors for PASC. Data were subjected to non-negative matrix factorization to identify symptom clusters, and a predictive model of PASC was developed. PASC prevalence was 11% (277/2,153), and of these patients, 66% (183/277) were considered asymptomatic at days 0-30. Five PASC symptom clusters emerged and specific symptoms at days 0-30 were associated with PASC. Women were more likely than men to develop PASC, with all age groups and ethnicities represented. PASC is a public health priority.}, } @article {pmid36154545, year = {2022}, author = {Hadda, V and Suri, TM and Iyer, H and Jain, A and Mittal, S and Madan, K and Mohan, A and Seith Bhalla, A and Sindhwani, G and Dutt, N and Venkatnarayan, K and Nath, A and Dhooria, S and Kumar, R and Marwah, V and Karmakar, S and Chaudhry, D and Ayub, II and Dwivedi, DP and Tiwari, P and Koul, P and Behera, AK and Saxena, P and Sengupta, A and Mohapatra, PR and Goyal, A and Christopher, DJ and Guleria, R}, title = {A Delphi consensus statement for the management of post-COVID interstitial lung disease.}, journal = {Expert review of respiratory medicine}, volume = {16}, number = {9}, pages = {983-995}, doi = {10.1080/17476348.2022.2128770}, pmid = {36154545}, issn = {1747-6356}, mesh = {Humans ; Delphi Technique ; *COVID-19/complications ; *Lung Diseases, Interstitial/diagnosis/epidemiology/etiology ; Consensus ; Lung/diagnostic imaging ; }, abstract = {INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach.

AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members.

EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.}, } @article {pmid36153556, year = {2022}, author = {Retornaz, F and Rebaudet, S and Stavris, C and Jammes, Y}, title = {Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {429}, pmid = {36153556}, issn = {1479-5876}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis ; Hand Strength ; Humans ; Myalgia/complications ; Retrospective Studies ; SARS-CoV-2 ; *Sleep Wake Disorders/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.

METHODS: This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.

RESULTS: The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.

CONCLUSIONS: These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.}, } @article {pmid36152884, year = {2022}, author = {Gómez-Carballa, A and Pardo-Seco, J and Pischedda, S and Rivero-Calle, I and Butler-Laporte, G and Richards, JB and Viz-Lasheras, S and Martinón-Torres, F and Salas, A and , }, title = {Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics.}, journal = {Environmental research}, volume = {215}, number = {Pt 2}, pages = {114288}, pmid = {36152884}, issn = {1096-0953}, mesh = {*COVID-19/complications/epidemiology/genetics ; *Coronavirus/genetics/metabolism ; *Coronavirus Infections ; DNA Methylation ; Epigenomics ; Female ; Genome-Wide Association Study ; Humans ; Male ; Toll-Like Receptor 7/genetics ; Transcriptome ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.}, } @article {pmid36151916, year = {2022}, author = {Harada, T and Schmitz, K and Helsper, CW and Campbell, G and Nekhlyudov, L}, title = {Long-COVID and long-term cancer survivorship-Shared lessons and opportunities.}, journal = {European journal of cancer care}, volume = {31}, number = {6}, pages = {e13712}, pmid = {36151916}, issn = {1365-2354}, mesh = {United States ; Humans ; *COVID-19 ; *Cancer Survivors ; SARS-CoV-2 ; *Neoplasms/therapy/epidemiology ; Europe ; }, abstract = {As of 2022, close to 90 million persons in the United States, 243 million persons in Europe and 585 million worldwide have been infected with the novel SARS-CoV-2 (COVID-19) virus and survived. Estimates vary but suggest that up to 50% may experience long-term sequelae, termed 'Long-COVID'. While Long-COVID is a new condition, the phenomenon of disabling long-term effects following an illness requiring ongoing surveillance and management is not. In this commentary, we discuss how Long-COVID parallels the experiences of long-term cancer survivors, highlight shared challenges and offer opportunities to improve research and clinical care for both growing populations of patients as well as other long-term chronic, disabling conditions.}, } @article {pmid36151607, year = {2022}, author = {Stute, NL and Szeghy, RE and Stickford, JL and Province, VP and Augenreich, MA and Ratchford, SM and Stickford, ASL}, title = {Longitudinal observations of sympathetic neural activity and hemodynamics during 6 months recovery from SARS-CoV-2 infection.}, journal = {Physiological reports}, volume = {10}, number = {18}, pages = {e15423}, pmid = {36151607}, issn = {2051-817X}, mesh = {Baroreflex/physiology ; Blood Pressure/physiology ; *COVID-19 ; Cross-Sectional Studies ; Heart Rate/physiology ; Hemodynamics/physiology ; Humans ; Muscle, Skeletal/physiology ; SARS-CoV-2 ; Sympathetic Nervous System/physiology ; Young Adult ; }, abstract = {Cross-sectional data indicate that acute SARS-CoV-2 infection increases resting muscle sympathetic nerve activity (MSNA) and alters hemodynamic responses to orthostasis in young adults. However, the longitudinal impact of contracting SARS-CoV-2 on autonomic function remains unclear. The aim of this study was to longitudinally track MSNA, sympathetic transduction to blood pressure (BP), and hemodynamics over 6 months following SARS-CoV-2 infection. Young adults positive with SARS-CoV-2 reported to the laboratory three times over 6 months (V1:41 ± 17, V2:108 ± 21, V3:173 ± 16 days post-infection). MSNA, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were measured at rest, during a cold pressor test (CPT), and at 30° head-up tilt (HUT). Basal SBP (p = 0.019) and DBP (p < 0.001) decreased throughout the 6 months, whereas basal MSNA and HR were not different. Basal sympathetic transduction to BP and estimates of baroreflex sensitivity did not change over time. SBP and DBP were lower during CPT (SBP: p = 0.016, DBP: p = 0.007) and HUT at V3 compared with V1 (SBP: p = 0.041, DBP: p = 0.017), with largely no changes in MSNA. There was a trend toward a visit-by-time interaction for burst incidence (p = 0.055) during HUT, wherein at baseline immediately prior to tilting, burst incidence was lower at V3 compared with V1 (p = 0.014), but there were no differences between visits in the 30 HUT position. These results support impairments to cardiovascular health, and potentially autonomic function, which may improve over time. However, the improvements in BP over 6 months recovery from mild SARS-CoV-2 infection are likely not a direct result of changes in sympathetic activity.}, } @article {pmid36150751, year = {2023}, author = {Alcindor, ML}, title = {Guidelines for diagnosing 'long Covid' in patients living with postacute sequelae of COVID-19 (PASC).}, journal = {Evidence-based nursing}, volume = {26}, number = {1}, pages = {20}, doi = {10.1136/ebnurs-2022-103538}, pmid = {36150751}, issn = {1468-9618}, mesh = {Humans ; *COVID-19/diagnosis ; COVID-19 Testing ; Patients ; *Post-Acute COVID-19 Syndrome ; }, } @article {pmid36148648, year = {2022}, author = {Pearson, M and Singh, P and Bartel, H and Crawford, P and Allsopp, G}, title = {Creative Long Covid: A qualitative exploration of the experience of Long Covid through the medium of creative narratives.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {25}, number = {6}, pages = {2950-2959}, pmid = {36148648}, issn = {1369-7625}, mesh = {Humans ; *COVID-19 ; Narration ; Writing ; Interpersonal Relations ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Healthcare is witnessing a new disease with the emergence of Long Covid; a condition which can result in myriad symptoms, varying in frequency and severity. As new data are emerging to help inform treatment guidelines, the perspectives of those living with Long Covid are essential in informing healthcare practice. The research aimed to collect the narratives of people living with Long Covid to better understand the lived experience of this condition. In attempting to narrate complex or traumatic experiences the arts and humanities can offer alternative ways of expressing embodied narratives, representing rich sources of meaning. Therefore, the research specifically sought to elicit creative expressions from participants with lived experience of Long Covid.

METHODS: Data were collected via an online repository where participants could submit their pieces of creative writing. Data were collected between August 2021 and January 2022 and a total of 28 submissions were received from participants. These were mostly written creative narratives. However, a small number were submitted as audio or video files of spoken word poetry or songs. Data collection was stopped once data saturation was achieved.

RESULTS: The submissions were subjected to thematic analysis and five themes were generated. These five themes are Identity, social relationships, symptoms, interaction with healthcare systems and time. The results provide an insight into the experience of Long Covid as detailed by the participants' creative narratives.

CONCLUSION: The results from this study provide a unique insight into the lived experience of Long Covid. In relation to clinical practice, the results suggest that adjustment reaction and loss of sense of self could be added as common symptoms.

Before undertaking the research, Long Covid community groups were contacted to discuss the potential value of this study and it was widely supported. One of the leading Long Covid support groups was also involved in disseminating information regarding the project. As part of ongoing work within this project, members of the team are actively disseminating the results within Long Covid communities and seeking to develop arts-based workshops specifically for people with Long Covid.}, } @article {pmid36148558, year = {2023}, author = {Takao, M and Ohira, M}, title = {Neurological post-acute sequelae of SARS-CoV-2 infection.}, journal = {Psychiatry and clinical neurosciences}, volume = {77}, number = {2}, pages = {72-83}, doi = {10.1111/pcn.13481}, pmid = {36148558}, issn = {1440-1819}, support = {3-8//Intramural fund from NCNP/ ; 22dk0307115h0001//Japan Agency for Medical Research and Development/ ; JP21wm0425019//Japan Agency for Medical Research and Development/ ; 18K06506//Japan Society for the Promotion of Science/ ; 21K06417//Japan Society for the Promotion of Science/ ; 22H04923//Japan Society for the Promotion of Science/ ; //NCNP/ ; //the Research Committee of Prion Disease and Slow Virus Infection/ ; Slow V//Health and Labour Sciences Research Grants/ ; //Ministry of Health, Labour and Welfare, Japan/ ; }, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Ambulatory Care Facilities ; Anxiety ; Disease Progression ; }, abstract = {The novel coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can have two phases: acute (generally 4 weeks after onset) and chronic (>4 weeks after onset). Both phases include a wide variety of signs and symptoms including neurological and psychiatric symptoms. The signs and symptoms that are considered sequelae of COVID-19 are termed post-COVID condition, long COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC). PASC symptoms include fatigue, dyspnea, palpitation, dysosmia, subfever, hypertension, alopecia, sleep problems, loss of concentration, amnesia, numbness, pain, gastrointestinal symptoms, depression, and anxiety. Because the specific pathophysiology of PASC has not yet been clarified, there are no definite criteria of the condition, hence the World Health Organization's definition is quite broad. Consequently, it is difficult to correctly diagnose PASC. Approximately 50% of patients may show at least one PASC symptom up to 12 months after COVID-19 infection; however, the exact prevalence of PASC has not been determined. Despite extensive research in progress worldwide, there are currently no clear diagnostic methodologies or treatments for PASC. In this review, we discuss the currently available information on PASC and highlight the neurological sequelae of COVID-19 infection. Furthermore, we provide clinical suggestions for diagnosing and caring for patients with PASC based on our outpatient clinic experience.}, } @article {pmid36148046, year = {2022}, author = {Blann, AD and Heitmar, R}, title = {SARS-CoV-2 and COVID-19: A Narrative Review.}, journal = {British journal of biomedical science}, volume = {79}, number = {}, pages = {10426}, pmid = {36148046}, issn = {2474-0896}, mesh = {*COVID-19/complications ; Humans ; Pandemics/prevention & control ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The World Health Organisation has reported that the viral disease known as COVID-19, caused by SARS-CoV-2, is the leading cause of death by a single infectious agent. This narrative review examines certain components of the pandemic: its origins, early clinical data, global and UK-focussed epidemiology, vaccination, variants, and long COVID.}, } @article {pmid36147602, year = {2022}, author = {Palomino-Kobayashi, LA and Ymaña, B and Ruiz, J and Mayanga-Herrera, A and Ugarte-Gil, MF and Pons, MJ}, title = {Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1000291}, pmid = {36147602}, issn = {2235-2988}, mesh = {Biomarkers ; *COVID-19/mortality ; Chemokine CCL5 ; Creatinine ; *Haptoglobins ; Humans ; Permeability ; Peru/epidemiology ; *Protein Precursors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Zonulin has previously been related to intestinal permeability in various inflammatory diseases, and more recently to the physiopathology of severe COVID-19 infections. We analysed serum samples from a previous study of a Peruvian cohort of hospitalised COVID-19 patients, for the quantification of zonulin by sandwich ELISA. Comparisons with clinical data, haematological and biochemical parameters and cytokine/chemokine levels were made. We found higher baseline zonulin levels in deceased patients, and zonulin was associated with fatal outcome in multivariable analyses, even after adjustment for age, gender, and obesity. There were also positive correlations between zonulin, creatinine, D-dimer values and prothrombin time, while inverse correlations were found for Sa/FiO2 ratio and CCL5 (RANTES). Further longitudinal studies are recommended to analyse the variation of zonulin levels over time as well as their relationship with long-COVID.}, } @article {pmid36146806, year = {2022}, author = {Jamoulle, M and Kazeneza-Mugisha, G and Zayane, A}, title = {Follow-Up of a Cohort of Patients with Post-Acute COVID-19 Syndrome in a Belgian Family Practice.}, journal = {Viruses}, volume = {14}, number = {9}, pages = {}, pmid = {36146806}, issn = {1999-4915}, mesh = {Adult ; Belgium/epidemiology ; *COVID-19/complications ; Family Practice ; Female ; Follow-Up Studies ; Humans ; Reproducibility of Results ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Fifty-five patients who suffered from COVID-19, who were still very ill after several months, with extreme fatigue, effort exhaustion, brain fog, anomia, memory disorder, anosmia, dysgeusia, and other multi-systemic health problems have been followed in a family practice setting between May 2021 and July 2022. Data extracted from the medical records of the 55 patients (40 women), mean age 42.4 (12 to 79 years), and a qualitative study of 6 of them using a semi-open-ended questionnaire allowed to highlight the clinical picture described by WHO as post-acute COVID-19 syndrome (PACS) also known as long COVID. We used brain single-photon emission computed tomography (SPECT-CT) in thirty-two patients with a high severity index and a highly impaired functional status, demonstrating vascular encephalopathy in twenty nine patients and supporting the hypothesis of a persistent cerebral vascular flow disorder in post COVID-19 condition. The patients will benefit from the consortium COVID Human Genetic Effort (covidhge.com) to explore the genetic and immunological basis of their problem, as 23/55 cases don't have immunological certainty of a COVID-19 infection. There is no known verified treatment. Analyzing the data from the first 52 patients, three categories of patients emerged over time: 16 patients made a full recovery after 6-8 months, 15 patients were able to return to life and work after 12-18 months with some sequelae, both groups being considered cured. In the third group, 21 patients are still very ill and unable to resume their work and life after 18 months. The biopsychosocial consequences on patients' lives are severe and family doctors are left out in the cold. It is necessary to test the reproducibility of this description, conducted on a small number of patients. Nevertheless, identifying, monitoring and supporting these patients is a necessity in family medicine.}, } @article {pmid36146672, year = {2022}, author = {Veronese, N and Bonica, R and Cotugno, S and Tulone, O and Camporeale, M and Smith, L and Trott, M and Bruyere, O and Mirarchi, L and Rizzo, G and Bavaro, DF and Barbagallo, M and Dominguez, LJ and Marotta, C and Silenzi, A and Nicastri, E and Saracino, A and Di Gennaro, F}, title = {Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review.}, journal = {Viruses}, volume = {14}, number = {9}, pages = {}, pmid = {36146672}, issn = {1999-4915}, mesh = {Adult ; *COVID-19/complications/therapy ; Female ; Humans ; Luteolin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19.

METHODS: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection.

RESULTS: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue.

CONCLUSION: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms.}, } @article {pmid36146560, year = {2022}, author = {Fernández-de-Las-Peñas, C and Ortega-Santiago, R and Fuensalida-Novo, S and Martín-Guerrero, JD and Pellicer-Valero, OJ and Torres-Macho, J}, title = {Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant.}, journal = {Vaccines}, volume = {10}, number = {9}, pages = {}, pmid = {36146560}, issn = {2076-393X}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; }, abstract = {This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in an urban hospital in Madrid, Spain. Individuals were classified as vaccinated if they received full administration (i.e., two doses) of BNT162b2 ("Pfizer-BioNTech") vaccines. Other vaccines were excluded. Those with just one dose of the BNT162b2 vaccine were considered as non-vaccinated. Patients were scheduled for a telephone interview at a follow-up around six months after infection for assessing the presence of post-COVID symptoms with particular attention to those symptoms starting after acute infection and hospitalization. Anxiety/depressive levels and sleep quality were likely assessed. Hospitalization and clinical data were collected from medical records. A total comprising 109 vaccinated and 92 non-vaccinated COVID-19 survivors was included. Vaccinated patients were older and presented a higher number of medical comorbidities, particular cardiorespiratory conditions, than non-vaccinated patients. No differences in COVID-19 onset symptoms at hospitalization and post-COVID symptoms six months after hospital discharge were found between vaccinated and non-vaccinated groups. No specific risk factor for any post-COVID symptom was identified in either group. This study observed that COVID-19 onset-associated symptoms and post-COVID symptoms six-months after hospitalization were similar between previously hospitalized COVID-19 survivors vaccinated and those non-vaccinated. Current data can be applied to the Delta variant and those vaccinated with BNT162b2 (Pfizer-BioNTech) vaccine.}, } @article {pmid36142282, year = {2022}, author = {Dybowska, M and Wyrostkiewicz, D and Opoka, L and Lewandowska, K and Sobiecka, M and Tomkowski, W and Szturmowicz, M}, title = {Venous Thromboembolic Disease in COVID-19, Pathophysiology, Therapy and Prophylaxis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142282}, issn = {1422-0067}, mesh = {Anticoagulants/therapeutic use ; *COVID-19/complications ; Heparin/therapeutic use ; Humans ; SARS-CoV-2 ; *Venous Thromboembolism/drug therapy/etiology/prevention & control ; *Venous Thrombosis/drug therapy ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {For over two years, the world has been facing the epidemiological and health challenge of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Growing problems are also complications after the development of COVID-19 in the form of post and long- COVID syndromes, posing a challenge for the medical community, both for clinicians and the scientific world. SARS-CoV-2 infection is associated with an increased risk of cardiovascular complications, especially thromboembolic complications, which are associated with both thrombosis of small and very small vessels due to immunothrombosis, and the development of venous thromboembolism. Low molecular wight heparin (LMHW) are the basic agents used in the prevention and treatment of thromboembolic complications in COVID-19. There is still a great deal of controversy regarding both the prevention and treatment of thromboembolic complications, including the prophylaxis dose or the optimal duration of anticoagulant treatment in patients with an episode of venous thromboembolism.}, } @article {pmid36141948, year = {2022}, author = {De Vincenzi, C and Pansini, M and Ferrara, B and Buonomo, I and Benevene, P}, title = {Consequences of COVID-19 on Employees in Remote Working: Challenges, Risks and Opportunities An Evidence-Based Literature Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {18}, pages = {}, pmid = {36141948}, issn = {1660-4601}, mesh = {*COVID-19/epidemiology ; Humans ; Mental Health ; Pandemics ; *Teleworking ; Workplace ; }, abstract = {The COVID-19 pandemic forced organizations across all sectors and sizes to undertake crucial changes in order to remain productive during the emergency. Among these, the shift towards remote working arrangements is still present in our workplaces, impacting employees' well-being and productivity. This systematic review aims to describe the pandemic's consequences on work organization by analyzing whether and how the shift towards remote or home-working impacted employees' productivity, performance, and well-being. Furthermore, it describes the role of individual and organizational factors in determining employees' adjustment to remote work. Sixty-seven peer-reviewed papers published from 2020 to 2022, written in English, were selected through the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Findings describe how remote working arrangements, the workplace and organizational factors, and the employees' individual traits and skills impacted employees' productivity and well-being. Furthermore, they provide a description of the organizational enforcement actions reported in the literature. Managerial and practical implications, such as enforcement actions, team management strategies, and initiatives to promote employees' physical and mental health, will be discussed in the paper.}, } @article {pmid36141935, year = {2022}, author = {Thomas, M}, title = {The Fatigue-Related Symptoms Post-Acute SARS-CoV-2: A Preliminary Comparative Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {18}, pages = {}, pmid = {36141935}, issn = {1660-4601}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/complications/etiology ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {A sizeable sub-group of individuals continue to experience persistent debilitating symptoms post-acute SARS-CoV-2. Although these can vary from person to person, fatigue appears to be the most common symptom. Post-viral fatigue has been documented in conditions such as influenza, infectious mononucleosis and more recently chronic fatigue syndrome (CFS). The current study uses measures that successfully describe the fatigue-related symptoms associated with CFS to investigate the fatigue experienced post-acute SARS-CoV-2. Twenty-six volunteers were recruited from Long COVID support groups active on social media. Data were collected anonymously using an online survey platform. These data were compared to pre-pandemic data from non-fatigued and CFS groups. The post-acute SARS-CoV-2 volunteers reported significantly higher levels of fatigue and cognitive difficulties than the non-fatigued controls. They also report more individual symptoms (such as lack of concentration) and problems with sleep quality. There was a similarity between the post-acute SARS-CoV-2 volunteers and the CFS group in terms of levels of depression, perceived stress, emotional distress and cognitive difficulties. Although this was a small-scale study, it demonstrates the range of symptoms experienced post-acute SARS-CoV-2. In addition, the similarities between this group and CFS suggests the need for further research into the mechanisms at play here, the need to identify those at risk of long-term symptoms and the development of possible interventions.}, } @article {pmid36141732, year = {2022}, author = {Fernández-de-Las-Peñas, C and Palacios-Ceña, M and Rodríguez-Jiménez, J and de-la-Llave-Rincón, AI and Fuensalida-Novo, S and Cigarán-Méndez, M and Florencio, LL and Ambite-Quesada, S and Ortega-Santiago, R and Pardo-Hernández, A and Hernández-Barrera, V and Palacios-Ceña, D and Gil-de-Miguel, Á}, title = {Psychometric Properties of the Functional Impairment Checklist (FIC) as a Disease-Specific Patient-Reported Outcome Measure (PROM) in Previously Hospitalized COVID-19 Survivors with Long-COVID.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {18}, pages = {}, pmid = {36141732}, issn = {1660-4601}, mesh = {Aged ; *COVID-19/complications/epidemiology ; Checklist ; Cohort Studies ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Reported Outcome Measures ; Psychometrics ; Reproducibility of Results ; SARS-CoV-2 ; Surveys and Questionnaires ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with a plethora of long-lasting symptoms (long-COVID). The presence of long-COVID symptoms causes decreased functionality. This study described the psychometric properties of the Functional Impairment Checklist (FIC), a disease-specific patient-reported outcome measure (PROM) used for evaluating the functional consequences of SARS in previously hospitalized COVID-19 survivors with long-COVID symptoms. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized with COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.4% women) COVID-19 survivors with long-COVID completed the FIC at a long-term follow-up after hospitalization (mean: 8.4 ± 1.5 months). Internal consistency (Cronbach alpha value), reliability (item-internal consistency, item-discriminant validity), construct validity (exploratory factor analysis), floor effect and ceiling effect were calculated. The mean time for fulfilling the FIC was 62 ± 11 s. The Cronbach's alpha values reflecting the internal consistency reliability were 0.864 for FIC-symptoms and 0.845 for FIC-disability. The correlation coefficient between the FIC-symptoms and FIC-disability scale was good (r: 0.676). The ceiling effect ranged from 2.29% to 9.02%, whereas the floor effect ranged from 38.56% to 80.19%. The exploratory factor analysis showed factor loadings from 0.514 to 0.866, supporting good construct validity. Women exhibited greater limitations in all physical symptoms and disability-related domains of the FIC compared with men (all, p < 0.001). Further, younger patients (those aged <45 years) self-reported lower physical symptoms and disability-related domains than older patients. In conclusion, this study indicates that the FIC has good psychometric properties to be used as a specific-disease PROM to measure function and disability in COVID-19 survivors with long-COVID.}, } @article {pmid36141693, year = {2022}, author = {Kersten, J and Hoyo, L and Wolf, A and Hüll, E and Nunn, S and Tadic, M and Scharnbeck, D and Rottbauer, W and Buckert, D}, title = {Cardiopulmonary Exercise Testing Distinguishes between Post-COVID-19 as a Dysfunctional Syndrome and Organ Pathologies.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {18}, pages = {}, pmid = {36141693}, issn = {1660-4601}, mesh = {*COVID-19/diagnosis ; Carbon Dioxide ; Dyspnea/diagnosis/etiology ; *Exercise Test/methods ; Humans ; Oxygen Consumption ; }, abstract = {(1) Background: Dyspnea is one of the most frequent symptoms among post-COVID-19 patients. Cardiopulmonary exercise testing (CPET) is key to a differential diagnosis of dyspnea. This study aimed to describe and classify patterns of cardiopulmonary dysfunction in post-COVID-19 patients, using CPET. (2) Methods: A total of 143 symptomatic post-COVID-19 patients were included in the study. All patients underwent CPET, including oxygen consumption, slope of minute ventilation to CO2 production, and capillary blood gas testing, and were evaluated for signs of limitation by two experienced examiners. In total, 120 patients reached a satisfactory level of exertion and were included in further analyses. (3) Results: Using CPET, cardiovascular diseases such as venous thromboembolism or ischemic and nonischemic heart disease were identified as either cardiac (4.2%) or pulmonary vascular (5.8%) limitations. Some patients also exhibited dysfunctional states, such as deconditioning (15.8%) or pulmonary mechanical limitation (9.2%), mostly resulting from dysfunctional breathing patterns. Most (65%) patients showed no signs of limitation. (4) Conclusions: CPET can identify patients with distinct limitation patterns, and potentially guide further therapy and rehabilitation. Dysfunctional breathing and deconditioning are crucial factors for the evaluation of post-COVID-19 patients, as they can differentiate these dysfunctional syndromes from organic diseases. This highlights the importance of dynamic (as opposed to static) investigations in the post-COVID-19 context.}, } @article {pmid36141012, year = {2022}, author = {Catalano, A and Iacopetta, D and Ceramella, J and Maio, AC and Basile, G and Giuzio, F and Bonomo, MG and Aquaro, S and Walsh, TJ and Sinicropi, MS and Saturnino, C and Geronikaki, A and Salzano, G}, title = {Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {18}, pages = {}, pmid = {36141012}, issn = {2304-8158}, support = {1062_R13_GREEN//Ministry of Education, Universities and Research/ ; }, abstract = {The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.}, } @article {pmid36139092, year = {2022}, author = {Lukiw, WJ and Jaber, VR and Pogue, AI and Zhao, Y}, title = {SARS-CoV-2 Invasion and Pathological Links to Prion Disease.}, journal = {Biomolecules}, volume = {12}, number = {9}, pages = {}, pmid = {36139092}, issn = {2218-273X}, support = {R01 AG018031/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; AG038834/NH/NIH HHS/United States ; AG18031/NH/NIH HHS/United States ; }, mesh = {Aged ; *COVID-19/complications ; Cytokine Release Syndrome ; Cytokines/metabolism ; *Encephalitis/complications ; Humans ; *Nervous System Diseases ; *Prion Diseases ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or impaired consciousness. Depending upon the patient’s age at the onset of COVID-19 and other factors, up to ~35% of all elderly COVID-19 patients develop a mild-to-severe encephalopathy due to complications arising from a SARS-CoV-2-induced cytokine storm and a surge in cytokine-mediated pro-inflammatory and immune signaling. In fact, this cytokine storm syndrome: (i) appears to predispose aged COVID-19 patients to the development of other neurological complications, especially those who have experienced a more serious grade of COVID-19 infection; (ii) lies along highly interactive and pathological pathways involving SARS-CoV-2 infection that promotes the parallel development and/or intensification of progressive and often lethal neurological conditions, and (iii) is strongly associated with the symptomology, onset, and development of human prion disease (PrD) and other insidious and incurable neurological syndromes. This commentary paper will evaluate some recent peer-reviewed studies in this intriguing area of human SARS-CoV-2-associated neuropathology and will assess how chronic, viral-mediated changes to the brain and CNS contribute to cognitive decline in PrD and other progressive, age-related neurodegenerative disorders.}, } @article {pmid36138753, year = {2022}, author = {McDaid, KM and Chopra, M}, title = {A Pilot Study to Examine If Dietary Habits Can Affect Symptomology in Mild Pre-Vaccination COVID-19 Cases.}, journal = {Biology}, volume = {11}, number = {9}, pages = {}, pmid = {36138753}, issn = {2079-7737}, abstract = {The heterogeneity of the severity of symptoms of COVID-19 experienced by the young and healthy individuals is poorly understood. The present study was undertaken to mainly examine whether the respective diets and the type of symptoms experienced by patients are predictive of having long COVID-19. Disease severity was assessed with a symptomatology questionnaire and used to group 55 participants in asymptomatic (AS), mild symptoms (S) and long COVID (LC). We found that experiencing a higher number of symptoms as well as fatigue were predictors of developing LC whereas those who experienced rhinorrhea were less likely to develop LC. Blood samples were also taken to measure vitamin D [25(OH)D] concentrations and duration of spike IgG antibodies. In this study, serum 25(OH)D was not significantly different between 3 symptom groups with median (IQR) ng/mL levels of 22.0 (12.3) in the AS, 22.3 (7.5) in S, and 24.9 (9.4) in the LC group (p ≥ 0.05). The duration of IgG antibody response was found to vary greatly, with some individuals showing raised IgG over a year after infection. To examine whether dietary factors can influence the severity of symptoms, diet was analysed using 4-7-day food diaries as well as a Food Frequency Questionnaire (FFQ). Some nutrients such as vitamin E, polyunsaturated fatty acids, fibre, and iron were associated with lower severity of COVID-19. Lower intake of vitamin E was associated with having LC with a median (IQR) intake of 6.2 mg (3.8) seen in LC vs. 8.6 mg (7.2) in the AS group (p = 0.047). This pilot study has highlighted a few differences in the number and type of symptoms experienced by the young non-hospitalised individuals with mild and long COVID-19 and identified a few dietary components for their potential protective role against long COVID-19, however, the findings need to be confirmed with further large scale studies.}, } @article {pmid36138727, year = {2022}, author = {Werner, S and Doerfel, C and Biedermann, R and Lorenz, M and Rasche, M and Proquitté, H and Newman, L and Vilser, D}, title = {The CSHQ-DE Questionnaire Uncovers Relevant Sleep Disorders in Children and Adolescents with Long COVID.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {9}, pages = {}, pmid = {36138727}, issn = {2227-9067}, abstract = {Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms, generally referred to as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared the sleep behavior at three different time points: pre-COVID-19; post-COVID-19 at the initial presentation; and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range: 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients; 11% experienced moderate disease. The initial presentation occurred at a median of 20.4 weeks (6 weeks-14 months) after the infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82 ± 8.7 points) to post-COVID-19 (49.40 ± 8.3 points; p ≤ 0.01). The score then normalized at re-presentation (46.98 ± 7.8; p = 0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data showed that children and adolescents with long COVID often suffer from sleep disturbances. For most children and adolescents, these sleep disorders decreased over time without any further medical intervention aside from a basic sleep consultation.}, } @article {pmid36137612, year = {2022}, author = {Greenhalgh, T and Sivan, M and Delaney, B and Evans, R and Milne, R}, title = {Long covid-an update for primary care.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {e072117}, doi = {10.1136/bmj-2022-072117}, pmid = {36137612}, issn = {1756-1833}, mesh = {*COVID-19/complications ; Humans ; Primary Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36137590, year = {2023}, author = {Son, K and Jamil, R and Chowdhury, A and Mukherjee, M and Venegas, C and Miyasaki, K and Zhang, K and Patel, Z and Salter, B and Yuen, ACY and Lau, KS and Cowbrough, B and Radford, K and Huang, C and Kjarsgaard, M and Dvorkin-Gheva, A and Smith, J and Li, QZ and Waserman, S and Ryerson, CJ and Nair, P and Ho, T and Balakrishnan, N and Nazy, I and Bowdish, DME and Svenningsen, S and Carlsten, C and Mukherjee, M}, title = {Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms.}, journal = {The European respiratory journal}, volume = {61}, number = {1}, pages = {}, doi = {10.1183/13993003.00970-2022}, pmid = {36137590}, issn = {1399-3003}, mesh = {Humans ; *Autoantibodies ; Post-Acute COVID-19 Syndrome ; Tumor Necrosis Factor-alpha ; Cough ; *COVID-19 ; Antibodies, Antinuclear ; Cytokines ; Fatigue ; }, abstract = {BACKGROUND: Autoimmunity has been reported in patients with severe coronavirus disease 2019 (COVID-19). We investigated whether anti-nuclear/extractable-nuclear antibodies (ANAs/ENAs) were present up to a year after infection, and if they were associated with the development of clinically relevant post-acute sequalae of COVID-19 (PASC) symptoms.

METHODS: A rapid-assessment line immunoassay was used to measure circulating levels of ANAs/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6 and 12 months post-recovery. Patient-reported fatigue, cough and dyspnoea were recorded at each time point. Multivariable logistic regression model and receiver operating curves were used to test the association of autoantibodies with patient-reported outcomes and pro-inflammatory cytokines.

RESULTS: Compared to age- and sex-matched healthy controls (n=22) and those who had other respiratory infections (n=34), patients with COVID-19 had higher detectable ANAs at 3 months post-recovery (p<0.001). The mean number of ANA autoreactivities per individual decreased between 3 and 12 months (from 3.99 to 1.55) with persistent positive titres associated with fatigue, dyspnoea and cough severity. Antibodies to U1-snRNP and anti-SS-B/La were both positively associated with persistent symptoms of fatigue (p<0.028, area under the curve (AUC) 0.86) and dyspnoea (p<0.003, AUC=0.81). Pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α and C-reactive protein predicted the elevated ANAs at 12 months. TNF-α, D-dimer and interleukin-1β had the strongest association with symptoms at 12 months. Regression analysis showed that TNF-α predicted fatigue (β=4.65, p=0.004) and general symptomaticity (β=2.40, p=0.03) at 12 months.

INTERPRETATION: Persistently positive ANAs at 12 months post-COVID are associated with persisting symptoms and inflammation (TNF-α) in a subset of COVID-19 survivors. This finding indicates the need for further investigation into the role of autoimmunity in PASC.}, } @article {pmid36136066, year = {2022}, author = {Churilov, LP and Normatov, MG and Utekhin, VJ}, title = {Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity?.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {29}, number = {3}, pages = {486-494}, pmid = {36136066}, issn = {1873-149X}, support = {№ 22-15-00113//Russian Sciense Foundation (https://rscf.ru/project/22-15-00113/)/ ; }, abstract = {Molecular mimicry between human and microbial/viral/parasite peptides is common and has long been associated with the etiology of autoimmune disorders provoked by exogenous pathogens. A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between the SARS-CoV-2 spike glycoprotein (S-protein) and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. A total of 14 pentapeptides shared by the SARS-CoV-2 S-protein, thyroid, pituitary, adrenal cortex autoantigens and beta-cells of the islets of Langerhans were identified, all of them belong to the immunoreactive epitopes of SARS-CoV-2. The discussion of the findings relates the results to the clinical correlates of COVID-19-associated autoimmune endocrinopathies. The most common of these illnesses is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to the marker autoantigens of this disease. The most important in pathogenesis of severe COVID-19, according to the authors, may be autoimmunity against adrenals because their adequate response prevents excessive systemic action of the inflammatory mediators causing cytokine storm and hemodynamic shock. A critique of the antigenic mimicry concept is given with an assertion that peptide sharing is not a guarantee but only a prerequisite for provoking autoimmunity based on the molecular mimicry. The latter event occurs in carriers of certain HLA haplotypes and when a shared peptide is only used in antigen processing.}, } @article {pmid36134915, year = {2022}, author = {Scarpino, I and Zucco, C and Vallelunga, R and Luzza, F and Cannataro, M}, title = {Investigating Topic Modeling Techniques to Extract Meaningful Insights in Italian Long COVID Narration.}, journal = {Biotech (Basel (Switzerland))}, volume = {11}, number = {3}, pages = {}, pmid = {36134915}, issn = {2673-6284}, abstract = {Through an adequate survey of the history of the disease, Narrative Medicine (NM) aims to allow the definition and implementation of an effective, appropriate, and shared treatment path. In the present study different topic modeling techniques are compared, as Latent Dirichlet Allocation (LDA) and topic modeling based on BERT transformer, to extract meaningful insights in the Italian narration of COVID-19 pandemic. In particular, the main focus was the characterization of Post-acute Sequelae of COVID-19, (i.e., PASC) writings as opposed to writings by health professionals and general reflections on COVID-19, (i.e., non-PASC) writings, modeled as a semi-supervised task. The results show that the BERTopic-based approach outperforms the LDA-base approach by grouping in the same cluster the 97.26% of analyzed documents, and reaching an overall accuracy of 91.97%.}, } @article {pmid36134517, year = {2023}, author = {Al-Hadrawi, DS and Al-Rubaye, HT and Almulla, AF and Al-Hakeim, HK and Maes, M}, title = {Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to Long COVID: A precision nomothetic approach.}, journal = {Acta neuropsychiatrica}, volume = {35}, number = {2}, pages = {76-87}, doi = {10.1017/neu.2022.21}, pmid = {36134517}, issn = {1601-5215}, mesh = {Humans ; Female ; *Fatigue Syndrome, Chronic/diagnosis ; Post-Acute COVID-19 Syndrome ; Oxygen Saturation ; Body Temperature ; Affective Symptoms ; *COVID-19/complications/diagnosis ; Biomarkers/metabolism ; Fatigue ; }, abstract = {BACKGROUND: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labelled as "physio-affective phenome") of LC has remained elusive.

OBJECTIVE: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

METHOD: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3-4 months later.

RESULTS: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques, we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterised by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

CONCLUSION: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.}, } @article {pmid36131932, year = {2022}, author = {Goh, D and Lim, JCT and Fernaíndez, SB and Joseph, CR and Edwards, SG and Neo, ZW and Lee, JN and Caballero, SG and Lau, MC and Yeong, JPS}, title = {Case report: Persistence of residual antigen and RNA of the SARS-CoV-2 virus in tissues of two patients with long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {939989}, pmid = {36131932}, issn = {1664-3224}, mesh = {Antibodies, Viral ; Antigens, Viral ; *COVID-19/complications ; Humans ; Nucleocapsid Proteins ; RNA, Viral ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The World Health Organization has defined long COVID-19 (LC) as a condition that occurs in individuals with a history of SARS-CoV-2 infection who exhibit persistent symptoms after its acute phase that last for at least two months and cannot be explained by an alternative diagnosis. Since we had previously reported residual viral antigens in tissues of convalescent patients, we aimed to assess the presence of such antigens in long COVID tissues. Here, we established the presence of the residual virus in the appendix, skin, and breast tissues of 2 patients who exhibited LC symptoms 163 and 426 days after symptom onset. With multiplex immunohistochemistry, we detected viral nucleocapsid protein in all three tissues. The nucleocapsid protein was further observed to colocalize with macrophage marker CD68, suggesting that immune cells were direct targets of SARS-CoV-2. Additionally, using RNAscope, the presence of viral RNA was also detected. Our positive finding in the breast tissue is corroborated by the recent reports of immunocompromised patients experiencing LC symptoms and persistent viral replication. Overall, our findings and emerging LC studies raise the possibility that the gastrointestinal tract may function as a reservoir for SARS-CoV-2.}, } @article {pmid36131349, year = {2022}, author = {Kimmig, LM and Rako, ZA and Ziegler, S and Richter, MJ and G S, AT and Roller, F and Grimminger, F and Vadász, I and Seeger, W and Herold, S and Tello, K and Matt, U}, title = {Long-term comprehensive cardiopulmonary phenotyping of COVID-19.}, journal = {Respiratory research}, volume = {23}, number = {1}, pages = {263}, pmid = {36131349}, issn = {1465-993X}, support = {413584448//Deutsche Forschungsgemeinschaft/ ; 390649896//Deutsche Forschungsgemeinschaft/ ; }, mesh = {COVID-19/*complications ; COVID-19 Testing ; Echocardiography ; *Exercise Test ; Humans ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Persistent symptoms after initial COVID-19 infection are common and are frequently referred to by the umbrella terms "post-COVID syndrome" and "long COVID". The sheer number of affected patients pose an increasing challenge to healthcare systems worldwide. To date, our understanding of the pathophysiology of the post-COVID syndrome remains poor and the extent to which persistent cardiopulmonary abnormalities contribute to the symptom complex is unclear. We sought to determine the presence and impact of cardiopulmonary sequelae after COVID-19 in longitudinal assessment.

METHODS: We report on 71 patients who underwent comprehensive, longitudinal testing in regular intervals for up to 12 months after their initial COVID-19 diagnosis. Testing included pulmonary function testing, cardiopulmonary exercise testing, dedicated left and right heart echocardiography, lung ultrasonography, and cardiac MRI.

RESULTS: Our results demonstrate that subjective quality of life after COVID-19 (EQ-5D visual acuity scale, VAS, 67.4 for patients treated as outpatient, 79.2 for patients admitted to the general floor, 71.8 for patients treated in an ICU) is not related to the severity of the initial infection. Maximal exercise capacity is also reduced (VO2max 79% predicted, SD ± 19%); however, this is driven in large parts by patients who had initially required ICU-level of care. The degree of objective reduction in exertion did not correlate with quality of life scores. Pulmonary function testing revealed mild and persistent reduction in DLCO over the first 12 months without significant restrictive or obstructive lung disease. Left and right heart function was intact with good RV function and intact RV/PA coupling, imaging findings suggestive of myocarditis were uncommon (7% of patients).

CONCLUSION: A reduction in exercise capacity after COVID-19 is common, but is most prominent in patients previously treated in the ICU and more likely related to deconditioning or fatigue than to cardiopulmonary impairment. Subjective quality of life scores are independent of the severity of initial infection and do not correlate with objective measures of cardiopulmonary function. In our cohort, persistent cardiopulmonary impairment after COVID-19 was uncommon. The post-COVID syndrome is unlikely to be the result of cardiopulmonary sequalae and may reflect a post-ICU syndrome in some. Trial registration Registered on clinicaltrials.gov (NCT04442789), Date: June 23, 2020.}, } @article {pmid36131342, year = {2022}, author = {Kruger, A and Vlok, M and Turner, S and Venter, C and Laubscher, GJ and Kell, DB and Pretorius, E}, title = {Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system.}, journal = {Cardiovascular diabetology}, volume = {21}, number = {1}, pages = {190}, pmid = {36131342}, issn = {1475-2840}, mesh = {Biomarkers ; C-Reactive Protein/metabolism ; *COVID-19/complications ; *Diabetes Mellitus, Type 2/complications ; Fibrin/metabolism ; Fibrinogen/metabolism ; Humans ; Interleukin-6 ; Plasma Kallikrein ; Platelet Factor 4 ; Proteomics ; *Thrombosis/diagnosis ; alpha-2-Antiplasmin ; von Willebrand Factor/analysis ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is a significant insoluble fibrin amyloid microclot load in the circulation of individuals with long COVID, and that these microclots entrap a substantial number of inflammatory molecules, including those that might prevent clot breakdown. Scientifically, the most challenging aspect of this debilitating condition is that traditional pathology tests such as a serum CRP (C-reactive protein) may not show any significant abnormal inflammatory markers, albeit these tests measure only the soluble inflammatory molecules. Elevated, or abnormal soluble biomarkers such as IL-6, D-Dimer or fibrinogen indicate an increased risk for thrombosis or a host immune response in COVID-19. The absence of biomarkers in standard pathology tests, result in a significant amount of confusion for patients and clinicians, as patients are extremely sick or even bed-ridden but with no regular identifiable reason for their disease. Biomarkers that are currently available cannot detect the molecules present in the microclots we identified and are therefore unable to confirm their presence or the mechanisms that drive their formation.

METHODS: Here we analysed the protein content of double-digested microclots of 99 long COVID patients and 29 healthy controls. The patients suffering from long COVID reported their symptoms through a questionnaire completed by themselves or their attending physician.

RESULTS: Our long COVID cohort's symptoms were found to be in line with global findings, where the most prevalent symptoms were constant fatigue (74%,) cognitive impairment (71%) and depression and anxiety (30%). Our most noteworthy findings were a reduced level of plasma Kallikrein compared to our controls, an increased level of platelet factor 4 (PF4) von Willebrand factor (VWF), and a marginally increased level of α-2 antiplasmin (α-2-AP). We also found a significant presence of antibodies entrapped inside these microclots.

CONCLUSION: Our results confirm the presence of pro-inflammatory molecules that may also contribute to a failed fibrinolysis phenomenon, which could possibly explain why individuals with long COVID suffer from chronic fatigue, dyspnoea, or cognitive impairment. In addition, significant platelet hyperactivation was noted. Hyperactivation will result in the granular content of platelets being shed into the circulation, including PF4. Overall, our results provide further evidence of both a failed fibrinolytic system in long COVID/PASC and the entrapment of many proteins whose presence might otherwise go unrecorded. These findings might have significant implications for individuals with pre-existing comorbidities, including cardiovascular disease and type 2 diabetes.}, } @article {pmid36131218, year = {2022}, author = {Feldman, DE and Boudrias, MH and Mazer, B}, title = {Long COVID symptoms in a population-based sample of persons discharged home from hospital.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {113}, number = {6}, pages = {930-939}, pmid = {36131218}, issn = {1920-7476}, mesh = {Adult ; Humans ; Female ; Male ; *COVID-19/epidemiology ; Patient Discharge ; Aftercare ; Depression/epidemiology ; Hospitals ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: The impact of long COVID among persons hospitalized and discharged home is unknown. We aimed to (1) report the prevalence of long COVID in persons hospitalized for COVID-19 and discharged home; (2) estimate the prevalence of physical, sensory, and psychological/mental health impairments; and (3) explore associated factors.

METHODS: We conducted a telephone survey of adult residents in Laval, Quebec, who were discharged home ≥ 2 months post-hospitalization for COVID-19. Participants responded to a standard questionnaire regarding persistent symptoms. We calculated the prevalence of long COVID and of persistent types of symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression.

RESULTS: In our sample (n = 398), 70% reported physical symptoms, 58% psychological problems, and 16% sensory impairments. 31.5% reported being troubled by persistent symptoms (long COVID). Factors associated with long COVID were a greater number of symptoms (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.69-2.28) and increased hospital stay (OR = 1.03, 95% CI = 1.01-1.06). Other factors associated with physical and psychological symptoms were female sex (OR = 2.17, 95% CI = 1.27-3.71 and OR = 2.06, 95% CI = 1.25-3.39; respectively), higher education level (OR = 2.10, 95% CI = 1.20-3.68 and OR = 2.43, 95% CI = 1.44-4.14; respectively), and obesity (OR = 1.95, 95% CI = 1.15-3.34 and OR = 1.70, 95% CI = 1.05-2.77; respectively).

CONCLUSION: In this population-based study of persons hospitalized for COVID-19 and discharged home, nearly one third were troubled by symptoms for 2 months or more post-discharge. There was a high proportion with persistent physical and psychological/mental health symptoms. Further research will assess the specific needs of these patients to inform health policy makers on service requirements for these persons.}, } @article {pmid36130797, year = {2022}, author = {Owens, B}, title = {How "long covid" is shedding light on postviral syndromes.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o2188}, doi = {10.1136/bmj.o2188}, pmid = {36130797}, issn = {1756-1833}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic ; *Frailty ; Humans ; RNA, Viral ; Virus Shedding ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36130738, year = {2022}, author = {, }, title = {The needs of patients with long covid must not be ignored.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o2287}, doi = {10.1136/bmj.o2287}, pmid = {36130738}, issn = {1756-1833}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36128513, year = {2022}, author = {, }, title = {Long Covid Europe patient group calls for greater regional collaboration and action at WHO European regional committee.}, journal = {The Lancet regional health. Europe}, volume = {21}, number = {}, pages = {100517}, pmid = {36128513}, issn = {2666-7762}, } @article {pmid36126984, year = {2022}, author = {Roehr, B}, title = {Long covid: protesters outside the White House demand better care.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o2266}, doi = {10.1136/bmj.o2266}, pmid = {36126984}, issn = {1756-1833}, } @article {pmid36126384, year = {2022}, author = {Kirschbaum, C}, title = {What to do now that hypocortisol appears to be a predominant sign of long COVID?.}, journal = {Psychoneuroendocrinology}, volume = {145}, number = {}, pages = {105919}, pmid = {36126384}, issn = {1873-3360}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Tomography, X-Ray Computed ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36125379, year = {2023}, author = {Heiss, R and Tan, L and Schmidt, S and Regensburger, AP and Ewert, F and Mammadova, D and Buehler, A and Vogel-Claussen, J and Voskrebenzev, A and Rauh, M and Rompel, O and Nagel, AM and Lévy, S and Bickelhaupt, S and May, MS and Uder, M and Metzler, M and Trollmann, R and Woelfle, J and Wagner, AL and Knieling, F}, title = {Pulmonary Dysfunction after Pediatric COVID-19.}, journal = {Radiology}, volume = {306}, number = {3}, pages = {e221250}, pmid = {36125379}, issn = {1527-1315}, mesh = {Adolescent ; Adult ; Child ; Humans ; Male ; *COVID-19 ; Cross-Sectional Studies ; Lung/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {Background Long COVID occurs at a lower frequency in children and adolescents than in adults. Morphologic and free-breathing phase-resolved functional low-field-strength MRI may help identify persistent pulmonary manifestations after SARS-CoV-2 infection. Purpose To characterize both morphologic and functional changes of lung parenchyma at low-field-strength MRI in children and adolescents with post-COVID-19 condition compared with healthy controls. Materials and Methods Between August and December 2021, a cross-sectional clinical trial using low-field-strength MRI was performed in children and adolescents from a single academic medical center. The primary outcome was the frequency of morphologic changes at MRI. Secondary outcomes included MRI-derived functional proton ventilation and perfusion parameters. Clinical symptoms, the duration from positive reverse transcriptase-polymerase chain reaction test result, and serologic parameters were compared with imaging results. Nonparametric tests for pairwise and corrected tests for groupwise comparisons were applied to assess differences in healthy controls, recovered participants, and those with long COVID. Results A total of 54 participants after COVID-19 infection (mean age, 11 years ± 3 [SD]; 30 boys [56%]) and nine healthy controls (mean age, 10 years ± 3; seven boys [78%]) were included: 29 (54%) in the COVID-19 group had recovered from infection and 25 (46%) were classified as having long COVID on the day of enrollment. Morphologic abnormality was identified in one recovered participant. Both ventilated and perfused lung parenchyma (ventilation-perfusion [V/Q] match) was higher in healthy controls (81% ± 6.1) compared with the recovered group (62% ± 19; P = .006) and the group with long COVID (60% ± 20; P = .003). V/Q match was lower in patients with time from COVID-19 infection to study participation of less than 180 days (63% ± 20; P = .03), 180-360 days (63% ± 18; P = .03), and 360 days (41% ± 12; P < .001) as compared with the never-infected healthy controls (81% ± 6.1). Conclusion Low-field-strength MRI showed persistent pulmonary dysfunction in children and adolescents who recovered from COVID-19 and those with long COVID. Clinical trial registration no. NCT04990531 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Paltiel in this issue.}, } @article {pmid36120804, year = {2022}, author = {Lee, J and Kwon, KH}, title = {Future perspective safe cosmetics: Focused on associated with ISO natural organic index.}, journal = {Journal of cosmetic dermatology}, volume = {21}, number = {12}, pages = {6619-6627}, doi = {10.1111/jocd.15398}, pmid = {36120804}, issn = {1473-2165}, mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Cosmetics/adverse effects ; Skin ; }, abstract = {BACKGROUND: As we enter the era of long COVID, recent studies on the relationship between coronavirus disease-19 (COVID-19) and skin are being conducted from various angles. Awareness of the safety of healthy skin is increasing.

OBJECTIVES: Therefore, in this study, we empirically analyzed safe cosmetics, natural cosmetics, and organic cosmetics, which have recently become a critical issue.

METHODS: Keywords such as 'long COVID', 'COVID-19 Skin', 'ISO Natural Organic Index', 'edible', 'safe cosmetics', 'natural cosmetics', and 'organic cosmetics' were searched and created. This study was conducted using PubMed, Google Scholar, Riss, Scopus, and ResearchGate. Accordingly, a total of 689 papers were studied. This paper was successfully completed using a total of 41 references in this study using PRISMA flow diagram.

RESULTS: In the long COVID era, customers in the beauty and cosmetics market will have to apply ISO natural organic ingredients to the cosmetics and beauty industry, reflecting consumer demand for edible ingredients for safety issues. Therefore, it will be able to provide new strategy and implications for a safer cosmetic market that values health and beauty.

CONCLUSION: Therefore, in this literature review, interest in skin has increased due to the long corona, and it was determined that changes in the cosmetic market would be necessary by using the ISO natural organic index for the consumer's desire for healthy skin. Therefore, in this article, in the future development of eco-friendly organic cosmetics, in line with the natural and environment-friendly changes reminiscent of the efficacy or ingredients of products, it is necessary to develop cosmetics using the ISO natural organic index that meets the needs of consumers and a differentiated strategy.}, } @article {pmid36120629, year = {2022}, author = {Tjahjadi, M and Caropeboka, S and Permana, C and Susanto, K and Susanto, E}, title = {Long-Delayed Manifestation of COVID-19 Coagulopathy Presenting with Severe Cerebral Venous Thrombosis Causes Massive Brain Hemorrhage.}, journal = {Asian journal of neurosurgery}, volume = {17}, number = {2}, pages = {342-346}, pmid = {36120629}, issn = {1793-5482}, abstract = {COVID-19 infection causes coagulopathy, which may lead to cerebral venous thrombotic (CVT) event. It usually occurs in patients with higher severity level of infection and manifests mostly within a month after the infection. However, in rare cases, the CVT may happen long after the infection and unrelated to the degree of the infection severity. We present the case of a previously healthy 62-year-old male patient with very mild COVID-19 symptoms that resolved in 3 weeks of home isolation treatment. Immediately after the infection, he developed hypercoagulability and was treated routinely with a novel oral anti-coagulant drug. Four months after the infection, he developed a worsening headache which, in several days, deteriorated to cause reduction in his consciousness level. Imaging showed a right temporoparietooccipital massive brain hemorrhage with right transverse and sigmoid sinus thrombosis. Emergency decompressive craniectomy was performed and the patient recovery was excellent. In patients with a hypercoagulable state after COVID-19 infection, the possibility of CVT event should be observed. It may not be related to the severity of the infection, and it may happen long after the infection.}, } @article {pmid36119337, year = {2022}, author = {Suresh, H and Nagaraja, MS}, title = {A study of clinical profile, sequelae of COVID, and satisfaction of inpatient care at a government COVID care hospital in Karnataka.}, journal = {Journal of family medicine and primary care}, volume = {11}, number = {6}, pages = {2672-2677}, pmid = {36119337}, issn = {2249-4863}, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 virus has increased the morbidity and mortality across the world. The most common symptoms are fever, dry cough, tiredness, and the least common symptoms are aches and pains, sore throat, diarrhoea, conjunctivitis, headache and loss of taste or smell. In this current pandemic, the number of COVID-19 survivors being discharged from the hospital is increasing day by day and the long-term effect among the survivors is also increasing. Fatigue and dyspnea were the most reported Post COVID symptoms. The presence of these symptoms is also known as "Long COVID". COVID-19 disease has not only affected the physical health but also the mental health of the patients which also had led to decrease in their quality of life.

MATERIAL AND METHODS: A retrospective cross-sectional study was conducted among 35 patients who were admitted in District hospital in Mysuru during the month of October 2020. Purposive Sampling was adopted for selecting the patients. Data was collected through telephone after their discharge. Data were entered in Microsoft Excel sheet and analysed using SPSS trial version 23. Descriptive statistics such as percentages and proportions were calculated. To see the association between the variables, Chi-square test, Fischer's exact test was used. P < 0.05 was taken as statistically significant.

RESULTS: The mean age of the study participants was 49.1 years. Majority of them had fever (68.6%) followed by Myalgia (65.7%), cough (60%), fatigue (42.9%), headache (37.1%) Majority of the patients had no symptoms after discharge (65.7%). After being discharged from the hospital, 22.9% of patients had difficulty in sleeping, 17.1% had loss of taste/smell and fatigue, 8.6% of them had breathlessness and 5.7% of the patients had a change in voice and loss of appetite.

CONCLUSION: With the increasing number of cases across the world, we will most likely face an ongoing wave of COVID-19 sequelae. To Prevent this, an extensive rehabilitation program is necessary for patients during hospitalization and after discharge.}, } @article {pmid36117492, year = {2022}, author = {Baig, AM}, title = {Differential diagnosis and pathogenesis of the neurological signs and symptoms in COVID-19 and long-COVID syndrome.}, journal = {CNS neuroscience & therapeutics}, volume = {28}, number = {12}, pages = {1905-1907}, pmid = {36117492}, issn = {1755-5949}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Pandemics ; Diagnosis, Differential ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurological features have now been reported very frequently in the ongoing COVID-19 pandemic caused by SARS-CoV-2. The neurological deficits associated features are observed in both acute and chronic stages of COVID-19 and they appear to overlap with wide-ranging symptoms that can be attributed to being of non-neural origins, thus obscuring the definitive diagnosis of neuro-COVID. The pathogenetic factors acting in concert to cause neuronal injury are now emerging, with SARS-CoV-2 directly affecting the brain coupled with the neuroinflammatory factors have been implicated in the causation of disabilities in acute COVID-19 and patients with Long-COVID syndrome. As the differentiation between a neural origin and other organ-based causation of a particular neurological feature is of prognostic significance, it implores a course of action to this covert, yet important neurological challenge.}, } @article {pmid36116186, year = {2022}, author = {Baumeister, A and Göritz, AS and Benoy, C and Jelinek, L and Moritz, S}, title = {Long-COVID or long before? Neurocognitive deficits in people with COVID-19.}, journal = {Psychiatry research}, volume = {317}, number = {}, pages = {114822}, pmid = {36116186}, issn = {1872-7123}, mesh = {Humans ; *COVID-19/complications ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {In connection with COVID-19 disease, evidence of persisting psychiatric and neurocognitive effects is accumulating. To examine long COVID symptoms, baseline data from 2015 (i.e., before the pandemic) and follow-up data from 2021 from 428 participants were compared. Participants with COVID-19 reported more subjective neurocognitive complaints in the follow-up, but this did not correspond to the test performance. Also, greater depressive symptoms compared with the no-COVID group were reported. However, these complaints must be put into perspective when considering the baseline data, since complaints were present before the COVID infection. Thus, premorbid performance as well as psychological factors should be considered when discussing long COVID.}, } @article {pmid36115083, year = {2022}, author = {Parodi, C and Viganò, I and Ottaviano, E and Massa, V and Borghi, E and Beretta, S and Di Francesco, JC and Badioni, V and Vignoli, A and , }, title = {Long-term analysis of the effects of COVID-19 in people with epilepsy: Results from a multicenter on-line survey across the pandemic waves.}, journal = {Epilepsy & behavior : E&B}, volume = {135}, number = {}, pages = {108900}, pmid = {36115083}, issn = {1525-5069}, mesh = {*COVID-19/complications/epidemiology ; COVID-19 Testing ; Communicable Disease Control ; *Epilepsy/psychology ; Humans ; Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: The worldwide pandemic caused by SARS-CoV-2 virus posed many challenges to the scientific and medical communities, including the protection and management of fragile populations. People with epilepsy (PWE) are a heterogenous group of subjects, with different treatment regimens and severity of symptoms. During the National lockdown, in Italy many patients with chronic conditions lost their regular follow-up program. The aim of this study was to investigate the impact of COVID-19 on their health status, from the start of the pandemic (March 2020) to July 2021 and one year later.

METHODS: We proposed an online questionnaire to subjects followed up at different epilepsy centers located in Milano, Monza & Lodi, three of Lombardy, Northern Italy, the most affected areas by the pandemic. Survey evaluated age, sex, characteristics of patients, type of epilepsy and therapies, COVID-19 diagnosis, vaccines, sleep quality, and anxiety status.

RESULTS: Among 178 analyzed surveys, 37 individuals reported symptoms of COVID-19 in closed contacts, including 9 with molecular diagnosis and 16 PWE performing the nasopharyngeal swab with 3 positive cases. One year later, 35 individuals reported at least one symptom overlapping with those typical of COVID-19, 8 received COVID-19 diagnosis, among which 6 were positive for SARS-CoV-2 infection. According to the sleep quality scale assessment, most PWE (52.3%) had poor sleep quality. Assessing anxiety status, 32 (38.1%) had a pathological score.

CONCLUSION: In this multicenter study, we observed that PWE do not appear to be at a higher risk of severe COVID-19. It will be fundamental monitoring this group to assess possible differences in long-COVID-19 and/or neuro-COVID-19 prevalence. On the other hand, our survey confirmed the impact of the pandemic on anxiety and quality of sleep in PWE. Thus, it is important to promptly recognize and treat psychological distress in PWE, because it could be a risk factor in seizure aggravation and quality-of-life deterioration. Telemedicine appears to be a useful tool to support patients with chronic diseases, such as epilepsy.}, } @article {pmid36114710, year = {2022}, author = {Yadav, AK and Mukherjee, G and Vasisht, K and Bobdey, S}, title = {Long COVID Among Moderate to Severe COVID-19 Cases in India During Second Wave of COVID-19.}, journal = {Asia-Pacific journal of public health}, volume = {34}, number = {8}, pages = {846-848}, pmid = {36114710}, issn = {1941-2479}, mesh = {Humans ; *COVID-19 ; Pandemics ; India/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36113745, year = {2022}, author = {Hsu, CK and Lai, CC}, title = {Confounding factors for developing long COVID.}, journal = {Pharmacological research}, volume = {184}, number = {}, pages = {106450}, doi = {10.1016/j.phrs.2022.106450}, pmid = {36113745}, issn = {1096-1186}, mesh = {*COVID-19/complications ; Humans ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36113246, year = {2022}, author = {Kumaria, A and Noah, A and Kirkman, MA}, title = {Does covid-19 impair endogenous neurogenesis?.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {105}, number = {}, pages = {79-85}, doi = {10.1016/j.jocn.2022.09.006}, pmid = {36113246}, issn = {1532-2653}, mesh = {*COVID-19/complications ; Humans ; *Neurodegenerative Diseases/therapy ; Neurogenesis/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Endogenous neural stem cells are thought to continue to generate new neurons throughout life in the human brain. Endogenous neurogenesis has been proposed to contribute to physiological roles in maintaining and regenerating olfaction, as well as promoting normal cognition, learning and memory. Specific impairments in these processes in COVID-19 - impaired olfaction and cognition - may implicate the SARS-CoV-2 virus in attenuating neurogenesis. Furthermore, neurogenesis has been linked with neuroregeneration; and impaired neuroregeneration has previously been linked with neurodegenerative diseases. Emerging evidence supports an association between COVID-19 infection and accelerated neurodegeneration. Also, structural changes indicating global reduction in brain size and specific reduction in the size of limbic structures - including orbitofrontal cortex, olfactory cortex and parahippocampal gyrus - as a result of SARS-CoV-2 infection have been demonstrated. This paper proposes the hypothesis that SARS-CoV-2 infection may impair endogenous neural stem cell activity. An attenuation of neurogenesis may contribute to reduction in brain size and/or neurodegenerative processes following SARS-CoV-2 infection. Furthermore, as neural stem cells are thought to be the cell of origin in glioma, better understanding of SARS-CoV-2 interaction with tumorigenic stem cells is indicated, with a view to informing therapeutic modulation. The subacute and chronic implications of attenuated endogenous neurogenesis are explored in the context of long COVID. Modulating endogenous neurogenesis may be a novel therapeutic strategy to address specific neurological manifestations of COVID-19 and potential applicability in tumour virotherapy.}, } @article {pmid36112333, year = {2022}, author = {Fagyas, M and Nagy, B and Ráduly, AP and Mányiné, IS and Mártha, L and Erdősi, G and Sipka, S and Enyedi, E and Szabó, AÁ and Pólik, Z and Kappelmayer, J and Papp, Z and Borbély, A and Szabó, T and Balla, J and Balla, G and Bai, P and Bácsi, A and Tóth, A}, title = {The majority of severe COVID-19 patients develop anti-cardiac autoantibodies.}, journal = {GeroScience}, volume = {44}, number = {5}, pages = {2347-2360}, pmid = {36112333}, issn = {2509-2723}, mesh = {Humans ; Aged ; Autoantibodies ; *Cardiomyopathy, Dilated ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Heart Failure ; Immunoglobulin G ; Immunoglobulin M ; *Aortic Valve Stenosis ; }, abstract = {Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, p = 0.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, p = 0.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, p = 0.03) and IgM (10%, p < 0.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment. Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65 years) and the patients younger than 65 years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).}, } @article {pmid36111386, year = {2022}, author = {Jimeno-Almazán, A and Franco-López, F and Buendía-Romero, Á and Martínez-Cava, A and Sánchez-Agar, JA and Sánchez-Alcaraz Martínez, BJ and Courel-Ibáñez, J and Pallarés, JG}, title = {Rehabilitation for post-COVID-19 condition through a supervised exercise intervention: A randomized controlled trial.}, journal = {Scandinavian journal of medicine & science in sports}, volume = {32}, number = {12}, pages = {1791-1801}, pmid = {36111386}, issn = {1600-0838}, support = {//Centro Médico Virgen de la Caridad/ ; //Ministerio de Ciencia e Innovación/ ; }, mesh = {Humans ; Quality of Life ; *COVID-19 ; Muscle Strength/physiology ; *Resistance Training ; Exercise Therapy/methods ; }, abstract = {PURPOSE: The aim of the study was to compare the outcomes of patients with post-COVID-19 condition undergoing supervised therapeutic exercise intervention or following the self-management WHO (World Health Organization) rehabilitation leaflet.

METHODS: A randomized controlled trial was carried out that included 39 participants with post-COVID-19 condition who had a chronic symptomatic phase lasting >12 weeks. Comprehensive medical screening, patient-reported symptoms, and cardiorespiratory fitness and muscular strength were assessed. Patients were randomly assigned to a tailored multicomponent exercise program based on concurrent training for 8 weeks (two supervised sessions per week comprised resistance training combined with aerobic training [moderate intensity variable training], plus a third day of monitored light intensity continuous training), or to a control group which followed the WHO guidelines for rehabilitation after COVID-19.

RESULTS: After follow-up, there were changes in physical outcomes in both groups, however, the magnitude of the change pre-post intervention favored the exercise group in cardiovascular and strength markers: VO2 max +5.7%, sit-to-stand -22.7% and load-velocity profiles in bench press +6.3%, and half squat +16.9%, (p < 0.05). In addition, exercise intervention resulted in a significantly better quality of life, less fatigue, less depression, and improved functional status, as well as in superior cardiovascular fitness and muscle strength compared to controls (p < 0.05). No adverse events were observed during the training sessions.

CONCLUSION: Compared to current WHO recommendations, a supervised, tailored concurrent training at low and moderate intensity for both resistance and endurance training is a more effective, safe, and well-tolerated intervention in post-COVID-19 conditions.}, } @article {pmid36111310, year = {2022}, author = {Shan, D and Liu, C and Li, S and Zheng, Y}, title = {Increased anxiety from fear of Omicron in China as compared to North America and Western Europe: A cross-sectional Kendall's tau-b analysis using the generalized anxiety disorder 7-item questionnaire.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {977361}, pmid = {36111310}, issn = {1664-0640}, abstract = {BACKGROUND: Policies dealing with the Coronavirus Disease 2019 (COVID-19) pandemic vary across the globe, the different governmental responses then affect the public perception of COVID-19. Many unofficial Chinese media outlets frequently spread misinformation about COVID-19 and exaggerated reports of rare sequelae of Omicron for monetization and attention seeking, leading to panics in the Chinese public. In comparison the attitudes toward Omicron in other countries around the world, especially in North America and Western Europe have shifted to a more relaxed stance.

OBJECTIVE: This article primarily aims to investigate the association between Chinese people's attitudes toward the potential after-effects of Omicron and their anxiety status, as compared to these of people living in North America or Western Europe.

METHODS: We conducted a questionnaire survey via the Credamo and collected valid data from 500 Chinese (not living in Shanghai), another 500 Chinese (living in Shanghai) and 500 people living in North America or Western Europe in June 2022. Kendall's coefficient of rank correlation tau-sub-b was used to examine this association.

RESULTS: The results suggested that subjective attitudes of Chinese participants toward the sequelae of Omicron were positively and significantly associated with their anxiety status [i.e., the Generalized Anxiety Disorder 7-item (GAD-7) scores] in Shanghai (China) (Tb = 0.44, p < 0.01) and other parts of China outside Shanghai (Tb = 0.37, p < 0.01). However, no such significant correlation was found in North America & Western Europe (Tb = -0.01, p > 0.05).

CONCLUSION: Our findings showed that Chinese participants who were more worried about the after-effects of Omicron had higher levels of anxiety. Although it is true that Long COVID-19 should be a concern, exaggerated media reporting can impact negatively on an individual's mental wellbeing. Only through the dissemination of robust scientific studies, the misinformation and the fears that follow it can be put to rest.}, } @article {pmid36109264, year = {2022}, author = {Alghamdi, F and Owen, R and Ashton, REM and Obotiba, AD and Meertens, RM and Hyde, E and Faghy, MA and Knapp, KM and Rogers, P and Strain, WD}, title = {Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services.}, journal = {Radiography (London, England : 1995)}, volume = {28 Suppl 1}, number = {}, pages = {S93-S99}, pmid = {36109264}, issn = {1532-2831}, mesh = {*COVID-19/complications/diagnostic imaging ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: The COVID-19 pandemic caused an unprecedented health crisis resulting in over 6 million deaths worldwide, a figure, which continues to grow. In addition to the excess mortality, there are individuals who recovered from the acute stages, but suffered long-term changes in their health post COVID-19, commonly referred to as long COVID. It is estimated there are currently 1.8 million long COVID sufferers by May 2022 in the UK alone. The aim of this narrative literature review is to explore the signs, symptoms and diagnosis of long COVID and the potential impact on imaging services.

KEY FINDINGS: Long COVID is estimated to occur in 9.5% of those with two doses of vaccination and 14.6% if those with a single dose or no vaccination. Long COVID is defined by ongoing symptoms lasting for 12 or more weeks post acute infection. Symptoms are associated with reductions in the quality of daily life and may involve multisystem manifestations or present as a single symptom.

CONCLUSION: The full impact of long COVID on imaging services is yet to be realised, but there is likely to be significant increased demand for imaging, particularly in CT for the assessment of lung disease. Educators will need to include aspects related to long COVID pathophysiology and imaging presentations in curricula, underpinned by the rapidly evolving evidence base.

IMPLICATIONS FOR PRACTICE: Symptoms relating to long COVID are likely to become a common reason for imaging, with a particular burden on Computed Tomography services. Planning, education and updating protocols in line with a rapidly emerging evidence base is going to be essential.}, } @article {pmid36108875, year = {2022}, author = {Trimarco, V and Izzo, R and Mone, P and Trimarco, B and Santulli, G}, title = {Targeting endothelial dysfunction and oxidative stress in Long-COVID.}, journal = {Pharmacological research}, volume = {184}, number = {}, pages = {106451}, pmid = {36108875}, issn = {1096-1186}, mesh = {*COVID-19/complications ; Endothelium, Vascular/metabolism ; Humans ; Oxidative Stress ; *Vascular Diseases/metabolism ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36108666, year = {2024}, author = {Llana, T and Zorzo, C and Mendez-Lopez, M and Mendez, M}, title = {Memory alterations after COVID-19 infection: a systematic review.}, journal = {Applied neuropsychology. Adult}, volume = {31}, number = {3}, pages = {292-305}, doi = {10.1080/23279095.2022.2123739}, pmid = {36108666}, issn = {2327-9109}, mesh = {Humans ; *COVID-19/complications ; *Memory Disorders/etiology ; Neuropsychological Tests ; }, abstract = {SARS-CoV-2 infection has a wide range of both acute and long-term symptoms. Memory alterations have been frequently reported in studies that explore cognition. The main objective of the systematic review is to update and further analyze the existing evidence of objective memory impairments in long-COVID-19 considering sample and study design characteristics, as well as to explore associations between memory performance and their epidemiological, clinical, and pathological features. A total of 13 studies were identified by searching in PubMed, Web of Science, and PsycInfo databases up to May 6, 2022. Most studies evaluated verbal component of memory in the short-term and long-term recall up to 30 min and mainly performed a single assessment completed at 4-6 months after the infection. The samples mainly consisted of middle-aged adults that required hospitalization. Samples were not stratified by sex, age, and severity. Poor verbal learning was reported in most cases (6-58%), followed by deficits in long-term (4-58%) and short-term (4-37%) verbal memory. Visuospatial component of memory was studied less than verbal component, showing impairment of long-term retention of visual items (10-49%). COVID-19 severity in the acute stage was not systematically associated with poor memory performance. Verbal memory deficits were associated with anxiety and depression. The existing literature on objective memory assessment in long-COVID suggests further research is warranted to confirm memory dysfunction in association with epidemiological, pathological, and clinical factors, using both verbal and visuospatial tests, and exploring in deep long-term memory deficits.}, } @article {pmid36108134, year = {2022}, author = {Mikuteit, M and Heinemann, S and Roder, S and Niewolik, J and Schröder, D and Vahldiek, K and Klawitter, S and Cossmann, A and Bergemann, T and Degen, C and Klawonn, F and Behrens, GMN and Müller, F and Dopfer-Jablonka, A and Steffens, S}, title = {Long-term Consequences of COVID-19 and the Pandemic: Protocol for a Web-Based, Longitudinal Observational Study (DEFEAT).}, journal = {JMIR research protocols}, volume = {11}, number = {10}, pages = {e38718}, pmid = {36108134}, issn = {1929-0748}, abstract = {BACKGROUND: With population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms.

OBJECTIVE: In this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic.

METHODS: With a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID.

RESULTS: Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database.

CONCLUSIONS: This study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID.

TRIAL REGISTRATION: German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt.

DERR1-10.2196/38718.}, } @article {pmid36108021, year = {2022}, author = {Couzin-Frankel, J}, title = {Private venture tackles Long Covid, aims to test drugs soon.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6612}, pages = {1245}, doi = {10.1126/science.ade8709}, pmid = {36108021}, issn = {1095-9203}, mesh = {*Antiviral Agents/therapeutic use ; *Biomedical Research ; *COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Initiative to explore whether coronavirus lingers in patients.}, } @article {pmid36107667, year = {2022}, author = {Mills, F and Bhogal, JK and Dennis, A and Spoiala, C and Milward, J and Saeed, S and Jones, LF and Weston, D and Carter, H}, title = {The effects of messaging on long COVID expectations: An online experiment.}, journal = {Health psychology : official journal of the Division of Health Psychology, American Psychological Association}, volume = {41}, number = {11}, pages = {853-863}, pmid = {36107667}, issn = {1930-7810}, support = {//National Institute for Health Research; Health Protection Research Units (HPRU)/ ; }, mesh = {*COVID-19/complications ; Humans ; Motivation ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: We examined whether varying information about long COVID would affect expectations about the illness.

METHOD: In October 2021, we conducted a 2 (Illness Description: long COVID vs. ongoing COVID-19 recovery) × 2 (Symptom Uncertainty: uncertainty emphasized vs. not emphasized) × 2 (Efficacy of Support: enhanced vs. basic support) between-subjects randomized online experimental study. Participants (N = 1,110) were presented with a scenario describing a positive COVID-19 test result, followed by one of eight scenarios describing a long COVID diagnosis and then completed outcome measures of illness expectations including: symptom severity, symptom duration, quality of life, personal control, treatment control, and illness coherence.

RESULTS: We ran a series of 2 × 2 × 2 ANOVAs on the outcome variables. We found a main effect of illness description: individuals reported longer symptom duration and less illness coherence when the illness was described as long COVID (compared to ongoing COVID-19 recovery). There was a main effect of symptom uncertainty: when uncertainty was emphasized, participants reported longer expected symptom duration (p < .001), less treatment control (p = .031), and less illness coherence (p < .001) than when uncertainty was not emphasized. There was a main effect of efficacy of support: participants reported higher personal control (p = .004) and higher treatment control (p = .037) when support was enhanced (compared to basic support).

CONCLUSIONS: Communications around long COVID should avoid emphasizing symptom uncertainty and aim to provide people with access to additional support and information on how they can facilitate their recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).}, } @article {pmid36107254, year = {2022}, author = {Pellegrino, R and Chiappini, E and Licari, A and Galli, L and Marseglia, GL}, title = {Prevalence and clinical presentation of long COVID in children: a systematic review.}, journal = {European journal of pediatrics}, volume = {181}, number = {12}, pages = {3995-4009}, pmid = {36107254}, issn = {1432-1076}, mesh = {Child ; Adolescent ; Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Prevalence ; Cross-Sectional Studies ; Communicable Disease Control ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: A systematic literature review was conducted up to 15th February 2022 to summarize long COVID evidence and to assess prevalence and clinical presentation in children and adolescents. Articles reporting long COVID prevalence and symptoms based on original data in the paediatric population were included. Case series quality was assessed through the JBI Critical Appraisal Checklist. For observational studies, adherence to STROBE checklist was evaluated. Twenty-two articles were included: 19 observational studies (12 cohort/7 cross-sectional) and 3 case series. Nine studies provided a control group. We found a high variability in terms of prevalence (1.6-70%). The most frequently reported symptoms were fatigue (2-87%), headache (3.5-80%), arthro-myalgias (5.4-66%), chest tightness or pain (1.4-51%), and dyspnoea (2-57.1%). Five studies reported limitations in daily function due to long COVID. Alterations at brain imaging were described in one study, transient electrocardiographic abnormalities were described in a minority of children, while most authors did not evidence long-term pulmonary sequelae. Older age, female sex, and previous long-term pathological conditions were more frequently associated with persistent symptoms.

CONCLUSION: Long COVID evidence in children is limited, heterogeneous, and based on low-quality studies. The lockdown consequences are difficult to distinguish from long COVID symptoms. High-quality studies are required: WHO definition of long COVID should be used, controlled clinical studies should be encouraged, and the impact of new variants on long COVID prevalence should be investigated to ensure an objective analysis of long COVID characteristics in children and a proper allocation of healthcare system resources.

WHAT IS KNOWN: • Children rarely develop a severe respiratory disease in the acute phase of COVID-19. • A limited number of patients develop a multisystem inflammatory condition that can lead to multiorgan failure and shock.

WHAT IS NEW: • Persistent symptoms after SARS-CoV-2 infection are reported in children and limitations in daily function due to long COVID symptoms affect school attendance. • Functional complaints of post-acute COVID are difficult to be distinguished from those due to social restrictions.}, } @article {pmid36106285, year = {2022}, author = {Chauhan, G and Upadhyay, A and Khanduja, S and Emerick, T}, title = {Stellate Ganglion Block for Anosmia and Dysgeusia Due to Long COVID.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27779}, pmid = {36106285}, issn = {2168-8184}, abstract = {Anosmia and parosmia refer to the loss or dysfunction of smell, respectively. Dysgeusia refers to taste disturbance. The coronavirus disease 2019 (COVID-19) pandemic and the subsequent phenomenon of Long COVID syndrome have been associated with an increased incidence of anosmia and dysgeusia. Smell and taste disturbances associated with COVID-19 are usually self-limiting but can persist for longer periods in some cases. Imbalances of the autonomic nervous system, especially dysregulation of the sympathetic system, are implicated in the persistence of anosmia and dysgeusia post-COVID-19 infection. Stellate ganglion block (SGB) can diminish the increased sympathetic activity and potentially resolve anosmia and dysgeusia occurring due to Long COVID. The authors report the successful resolution of persistent anosmia and dysgeusia due to Long COVID in a female patient after she underwent SGB.}, } @article {pmid36106228, year = {2022}, author = {Okuda, H and Kunieda, C and Shibata, H and Ohashi, T and Ogawa, T}, title = {Bilateral Recurrent Laryngeal Nerve Paralysis Manifesting as Long COVID.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27792}, pmid = {36106228}, issn = {2168-8184}, abstract = {Management with ventilation is used for severe cases of coronavirus disease 2019 (COVID-19). After extubation, recurrent laryngeal nerve paralysis due to various factors may occur. Almost all cases of paralysis develop unilaterally; however, bilateral recurrent laryngeal nerve paralysis occurs rarely. Such cases may be fatal due to upper air obstruction, and patients are forced to adhere to restrictions after a tracheotomy. The present case illustrates bilateral recurrent laryngeal nerve paralysis that occurred 48 hours after withdrawal from the ventilator. A 75-year-old woman with a history of hypertension came to our hospital with a history of fever and cough for five days. She was diagnosed with pneumonia due to COVID-19 via polymerase chain reaction using her saliva, and ground-glass opacity was found in both lung fields on chest X-ray and computed tomography (CT). Mechanical ventilation, steroids, remdesivir, and baricitinib were administered. The patient's fever and oxygenation status improved with these treatments, and she was weaned from the ventilator on the eighth day of hospitalization. She had no symptoms immediately. However, 48 hours after extubation, bilateral recurrent laryngeal nerve paralysis was suspected. Thus, oral intubation was immediately introduced and a tracheostomy was performed. Vocal cord movement disorders continued for eight weeks, and during that period, the patient displayed hoarseness and suffered from dysphagia. We considered that nerve disorders from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in addition to the compression by the endotracheal tube, caused bilateral recurrent laryngeal nerve paralysis. The neural injury by SARS-CoV-2 may prolong and manifest as "Long COVID."}, } @article {pmid36104031, year = {2022}, author = {Wise, J}, title = {Covid-19: WHO urges action as 17 million long covid cases are estimated in Europe.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o2232}, doi = {10.1136/bmj.o2232}, pmid = {36104031}, issn = {1756-1833}, mesh = {*COVID-19/complications ; Europe/epidemiology ; Humans ; World Health Organization ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36103880, year = {2022}, author = {Wild, CJ and Norton, L and Menon, DK and Ripsman, DA and Swartz, RH and Owen, AM}, title = {Disentangling the cognitive, physical, and mental health sequelae of COVID-19.}, journal = {Cell reports. Medicine}, volume = {3}, number = {10}, pages = {100750}, pmid = {36103880}, issn = {2666-3791}, mesh = {Adult ; Humans ; Neuropsychological Tests ; *Mental Health ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Cognition ; }, abstract = {As COVID-19 cases exceed hundreds of millions globally, many survivors face cognitive challenges and prolonged symptoms. However, important questions about the cognitive effects of COVID-19 remain unresolved. In this cross-sectional online study, 478 adult volunteers who self-reported a positive test for COVID-19 (mean = 30 days since most recent test) perform significantly worse than pre-pandemic norms on cognitive measures of processing speed, reasoning, verbal, and overall performance, but not short-term memory, suggesting domain-specific deficits. Cognitive differences are even observed in participants who did not require hospitalization. Factor analysis of health- and COVID-related questionnaires reveals two clusters of symptoms-one that varies mostly with physical symptoms and illness severity, and one with mental health. Cognitive performance is positively correlated with the global measure encompassing physical symptoms, but not the one that broadly describes mental health, suggesting that the subjective experience of "long COVID" relates to physical symptoms and cognitive deficits, especially executive dysfunction.}, } @article {pmid36103031, year = {2023}, author = {Picone, P and Sanfilippo, T and Guggino, R and Scalisi, L and Monastero, R and Baschi, R and Mandalà, V and San Biagio, L and Rizzo, M and Giacomazza, D and Dispenza, C and Nuzzo, D}, title = {Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.}, journal = {Cellular and molecular neurobiology}, volume = {43}, number = {5}, pages = {1685-1695}, pmid = {36103031}, issn = {1573-6830}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Mental Health ; Post-Acute COVID-19 Syndrome ; Pandemics ; }, abstract = {SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.}, } @article {pmid36101871, year = {2022}, author = {O' Mahony, L and Buwalda, T and Blair, M and Forde, B and Lunjani, N and Ambikan, A and Neogi, U and Barrett, P and Geary, E and O'Connor, N and Dineen, J and Clarke, G and Kelleher, E and Horgan, M and Jackson, A and Sadlier, C}, title = {Impact of Long COVID on health and quality of life.}, journal = {HRB open research}, volume = {5}, number = {}, pages = {31}, pmid = {36101871}, issn = {2515-4826}, abstract = {Background: The aim of this study was to measure the impact of post-acute sequelae of COVID-19 (PASC) on quality of life, mental health, ability to work and return to baseline health in an Irish cohort. Methods: We invited individuals with symptoms of COVID-19 lasting more than 14 days to participate in an anonymous online questionnaire. Basic demographic data and self-reported symptoms were recorded. Internationally validated instruments including the patient health questionnaire somatic, anxiety and depressive symptom scales (PHQ-SADS), the Patient Health Questionnaire-15 (PHQ-15) and Chadler fatigue scale (CFQ) were used. Results: We analysed responses from 988 participants with self-reported confirmed (diagnostic/antibody positive; 81%) or suspected (diagnostic/antibody negative or untested; 9%) COVID-19. The majority of respondents were female (88%), white (98%), with a median age of 43.0 (range 15 - 88 years old) and a median BMI of 26.0 (range 16 - 60). At the time of completing this survey, 89% of respondents reported that they have not returned to their pre-COVID-19 level of health. The median number of symptoms reported was 8 (range 0 to 33 symptoms), with a median duration of 12 months (range 1 to 20 months) since time of acute infection. A high proportion of PASC patients reported that they have a moderate or severe limitation in their ability to carry out their usual activities, 38% report their ability to work is severely limited and 33% report a moderate, or higher, level of anxiety or depression. Conclusion: The results of this survey of an Irish cohort with PASC are in line with reports from other settings, and we confirm that patients with PASC reported prolonged, multi-system symptoms which can significantly impact quality of life, affect ability to work and cause significant disability. Dedicated multidisciplinary, cross specialty supports are required to improve outcomes of this patient group.}, } @article {pmid36100326, year = {2022}, author = {Sukocheva, OA and Maksoud, R and Beeraka, NM and Madhunapantula, SV and Sinelnikov, M and Nikolenko, VN and Neganova, ME and Klochkov, SG and Amjad Kamal, M and Staines, DR and Marshall-Gradisnik, S}, title = {Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Journal of advanced research}, volume = {40}, number = {}, pages = {179-196}, pmid = {36100326}, issn = {2090-1224}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic ; Humans ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

AIMS OF REVIEW: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology.

The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.}, } @article {pmid36098262, year = {2022}, author = {Stephenson, T and Shafran, R and Ladhani, SN}, title = {Long COVID in children and adolescents.}, journal = {Current opinion in infectious diseases}, volume = {35}, number = {5}, pages = {461-467}, pmid = {36098262}, issn = {1473-6527}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Female ; Humans ; Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Although acute COVID-19 has been milder in children and young people compared with adults, there is a concern that they may suffer persistent symptoms. There is a need to define the clinical phenotype, determine those most at risk, the natural course of the condition and evaluate preventive and therapeutic strategies for both mental health and physical symptoms.

RECENT FINDINGS: More recent studies with control groups reported a lower prevalence of persistent symptoms in children and young people exposed to SARS-CoV-2. A systematic review and meta-analysis found that the frequency of the majority of reported persistent symptoms is similar in SARS-CoV-2 positive cases and controls. Children and young people infected with SARS-COV-2 had small but significant increases in persisting cognitive difficulties, headache and loss of smell. Factors associated with persisting, impairing symptoms include increased number of symptoms at the time of testing, female sex, older age, worse self-rated physical and mental health, and feelings of loneliness preinfection.

SUMMARY: This review highlights the importance of a control group in studies following SARS-CoV-2 infection, the need for case definitions and research to understand the outcomes of long COVID in children and young people.}, } @article {pmid36096146, year = {2023}, author = {Amir, O and Goldberg, Y and Mandel, M and Bar-On, YM and Bodenheimer, O and Freedman, L and Ash, N and Alroy-Preis, S and Huppert, A and Milo, R}, title = {Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study.}, journal = {The Lancet. Infectious diseases}, volume = {23}, number = {1}, pages = {67-73}, pmid = {36096146}, issn = {1474-4457}, mesh = {Humans ; Adolescent ; Child ; *COVID-19/epidemiology/prevention & control ; SARS-CoV-2 ; Israel/epidemiology ; Post-Acute COVID-19 Syndrome ; BNT162 Vaccine ; }, abstract = {BACKGROUND: The BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. We aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents.

METHODS: In this observational cohort study, we extracted data for the omicron-dominated (sublineage BA.1) period. We compared rates of confirmed SARS-CoV-2 infection between children aged 5-10 years 14-35 days after receiving the second vaccine dose with an internal control group of children 3-7 days after receiving the first dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents aged 12-15 years 14-60 days after receiving a booster dose with an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure.

FINDINGS: Between Dec 26, 2021, and Jan 8, 2022, we included 1 158 289 participants. In children aged 5-10 years, the adjusted rate of confirmed infection was 2·3 times (95% CI 2·0-2·5) lower in children who received a second dose than in the internal control group. The adjusted infection rate in children who received a second dose was 102 infections per 100 000 risk-days (94-110) compared with 231 infections per 100 000 risk-days (215-248) in the corresponding internal control cohort. In adolescents aged 12-15 years, the booster dose decreased confirmed infection rates by 3·3 times (2·8-4·0) compared with in the internal control group. The adjusted infection rate of the booster cohort was 70 per 100 000 risk-days (60-81) compared with 232 per 100 000 risk-days (212-254) in the internal control cohort.

INTERPRETATION: A recent two-dose vaccination regimen with BNT162b2 and a recent booster dose in adolescents substantially reduced the rate of confirmed infection compared with the internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and long-COVID.

FUNDING: None.}, } @article {pmid36094442, year = {2022}, author = {Brehon, K and Niemeläinen, R and Hall, M and Bostick, GP and Brown, CA and Wieler, M and Gross, DP}, title = {Return-to-Work Following Occupational Rehabilitation for Long COVID: Descriptive Cohort Study.}, journal = {JMIR rehabilitation and assistive technologies}, volume = {9}, number = {3}, pages = {e39883}, pmid = {36094442}, issn = {2369-2529}, abstract = {BACKGROUND: Emerging evidence suggests that worldwide, between 30% and 50% of those who are infected with COVID-19 experience long COVID (LC) symptoms. These symptoms create challenges with return-to-work (RTW) in a high proportion of individuals with LC. To tailor rehabilitation programs to LC sequelae and help improve RTW outcomes, more research on LC rehabilitation program outcomes is needed.

OBJECTIVE: This study describes the characteristics and outcomes of workers who participated in an LC occupational rehabilitation program.

METHODS: A cohort study was conducted. Descriptive variables included demographic and occupational factors as well as patient-reported outcome measures (PROMs, ie, the Fatigue Severity Scale [FSS], the Post-COVID Functional Scale [PCFS], the 36-item Short Form Health Survey [SF-36], the Pain Disability Index [PDI], the pain Visual Analogue Scale [VAS], the 9-item Patient Health Questionnaire [PHQ-9], the 7-item Generalized Anxiety Disorder Questionnaire [GAD-7], and the Diagnostic and Statistical Manual for Mental Disorders Fifth Edition [DSM-5] posttraumatic stress disorder [PTSD] checklist [PCL-5]). The main outcome variable was the RTW status at discharge. Descriptive statistics were calculated. Logistic regression examined predictors of RTW.

RESULTS: The sample consisted of 81 workers. Most workers were female (n=52, 64%) and from health-related occupations (n=43, 53%). Only 43 (53%) individuals returned to work at program discharge, with 40 (93%) of these returning to modified duties. Although there were statistically significant improvements on the pain VAS (mean 11.1, SD 25.6, t31=2.5, P=.02), the PDI (mean 9.4, SD 12.5, t32=4.3, P<.001), the FSS (mean 3.9, SD 8.7, t38=2.8, P=.01), the SF-36 PCS (mean 4.8, SD 8.7, t38=-3.5, P=.001), the PHQ-9 (mean 3.7, SD 4.0, t31=5.2, P<.001), and the GAD-7 (mean 1.8, SD 4.4, t22=1.8, P=.03), there were no significant improvements in the PCFS, the overall mental component score (MCS) of the SF-36, or on the PCL-5. The availability of modified duties (odds ratio [OR] 3.38, 95% CI 1.26-9.10) and shorter time between infection and admission for rehabilitation (OR 0.99, 95% CI 0.99-1.00) predicted RTW even when controlling for age and gender.

CONCLUSIONS: Workers undergoing LC rehabilitation reported significant but modest improvements on a variety of PROMs, but only 43 (53%) returned to work. Outcomes would likely improve with increased availability of modified duties and timelier rehabilitation. Additional research is needed, including larger observational cohorts as well as randomized controlled trials to evaluate the effectiveness of LC rehabilitation.}, } @article {pmid36093345, year = {2022}, author = {Pfaff, ER and Madlock-Brown, C and Baratta, JM and Bhatia, A and Davis, H and Girvin, A and Hill, E and Kelly, L and Kostka, K and Loomba, J and McMurry, JA and Wong, R and Bennett, TD and Moffitt, R and Chute, CG and Haendel, M and , and , }, title = {Coding Long COVID: Characterizing a new disease through an ICD-10 lens.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36093345}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Naming a newly discovered disease is a difficult process; in the context of the COVID-19 pandemic and the existence of post-acute sequelae of SARS-CoV-2 infection (PASC), which includes Long COVID, it has proven especially challenging. Disease definitions and assignment of a diagnosis code are often asynchronous and iterative. The clinical definition and our understanding of the underlying mechanisms of Long COVID are still in flux, and the deployment of an ICD-10-CM code for Long COVID in the US took nearly two years after patients had begun to describe their condition. Here we leverage the largest publicly available HIPAA-limited dataset about patients with COVID-19 in the US to examine the heterogeneity of adoption and use of U09.9, the ICD-10-CM code for "Post COVID-19 condition, unspecified."

METHODS: We undertook a number of analyses to characterize the N3C population with a U09.9 diagnosis code (n = 21,072), including assessing person-level demographics and a number of area-level social determinants of health; diagnoses commonly co-occurring with U09.9, clustered using the Louvain algorithm; and quantifying medications and procedures recorded within 60 days of U09.9 diagnosis. We stratified all analyses by age group in order to discern differing patterns of care across the lifespan.

RESULTS: We established the diagnoses most commonly co-occurring with U09.9, and algorithmically clustered them into four major categories: cardiopulmonary, neurological, gastrointestinal, and comorbid conditions. Importantly, we discovered that the population of patients diagnosed with U09.9 is demographically skewed toward female, White, non-Hispanic individuals, as well as individuals living in areas with low poverty, high education, and high access to medical care. Our results also include a characterization of common procedures and medications associated with U09.9-coded patients.

CONCLUSIONS: This work offers insight into potential subtypes and current practice patterns around Long COVID, and speaks to the existence of disparities in the diagnosis of patients with Long COVID. This latter finding in particular requires further research and urgent remediation.}, } @article {pmid36092770, year = {2022}, author = {Au, L and Capotescu, C and Eyal, G and Finestone, G}, title = {Long covid and medical gaslighting: Dismissal, delayed diagnosis, and deferred treatment.}, journal = {SSM. Qualitative research in health}, volume = {2}, number = {}, pages = {100167}, pmid = {36092770}, issn = {2667-3215}, abstract = {While we know a lot more about Long Covid today, patients who were infected with Covid-19 early on in the pandemic and developed Long Covid had to contend with medical professionals who lacked awareness of the potential for extended complications from Covid-19. Long Covid patients have responded by labeling their contentious interactions with medical professionals, organizations, and the broader medical system as "gaslighting." We argue that the charge of medical gaslighting can be understood as a form of ontological politics. Not only do patients demand that their version of reality be recognized, but they also blame the experts who hold gatekeeping power over their medical care for producing a distorted version of said reality. By analyzing results from an online survey of Long Covid patients active on social media in the United States (n = 334), we find that experiences of contention and their reframing as "gaslighting" were common amongst our respondents. In short answer responses about their experience obtaining medical care for Long Covid, our respondents described encountering medical professionals who dismissed their experience, leading to lengthy diagnostic odysseys and lack of treatment options for Long Covid. Even though we are limited by characteristics of our sample, there is good reason to believe that these experiences and their contentious reframing as medical gaslighting are exacerbated by gender, class, and racial inequalities.}, } @article {pmid36091834, year = {2022}, author = {Chen, W and Yao, M and Chen, M and Ou, Z and Yang, Q and He, Y and Zhang, N and Deng, M and Wu, Y and Chen, R and Tan, X and Kong, Z}, title = {Using an untargeted metabolomics approach to analyze serum metabolites in COVID-19 patients with nucleic acid turning negative.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {964037}, pmid = {36091834}, issn = {1663-9812}, abstract = {Background: The coronavirus disease of 2019 (COVID-19) is a severe public health issue that has infected millions of people. The effective prevention and control of COVID-19 has resulted in a considerable increase in the number of cured cases. However, little research has been done on a complete metabonomic examination of metabolic alterations in COVID-19 patients following treatment. The current project pursues rigorously to characterize the variation of serum metabolites between healthy controls and COVID-19 patients with nucleic acid turning negative via untargeted metabolomics. Methods: The metabolic difference between 20 COVID-19 patients (CT ≥ 35) and 20 healthy controls were investigated utilizing untargeted metabolomics analysis employing High-resolution UHPLC-MS/MS. COVID-19 patients' fundamental clinical indicators, as well as health controls, were also collected. Results: Out of the 714 metabolites identified, 203 still significantly differed between COVID-19 patients and healthy controls, including multiple amino acids, fatty acids, and glycerophospholipids. The clinical indexes including monocytes, lymphocytes, albumin concentration, total bilirubin and direct bilirubin have also differed between our two groups of participators. Conclusion: Our results clearly showed that in COVID-19 patients with nucleic acid turning negative, their metabolism was still dysregulated in amino acid metabolism and lipid metabolism, which could be the mechanism of long-COVID and calls for specific post-treatment care to help COVID-19 patients recover.}, } @article {pmid36091707, year = {2022}, author = {Trott, M and Driscoll, R and Pardhan, S}, title = {The prevalence of sensory changes in post-COVID syndrome: A systematic review and meta-analysis.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {980253}, pmid = {36091707}, issn = {2296-858X}, abstract = {UNLABELLED: Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total n 4,707; median n per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7-16.6%), hyposmia 29.9% (95% CI 19.9-40%), ageusia 11.7% (95% CI 6.1-17.3%), and hypogeusia 31.2% (95% 16.4-46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms.

[www.crd.york.ac.uk/prospero], identifier [CRD42021292804].}, } @article {pmid36091550, year = {2022}, author = {Ma, H and Ma, Y and Ge, S and Wang, S and Zhao, IY and Christensen, M}, title = {Intrapersonal and interpersonal level factors influencing self-care practices among Hong Kong individuals with COVID-19-A qualitative study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {964944}, pmid = {36091550}, issn = {2296-2565}, mesh = {*COVID-19/complications ; Hong Kong ; Humans ; Pandemics ; Self Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The unprecedented crisis during the fifth wave of the COVID-19 pandemic in Hong Kong placed a significant burden on the health care system. Therefore, the Hong Kong government advocated that individuals with no or mild COVID-19 symptoms should self-care at home. This study aimed to understand intrapersonal and interpersonal level factors that shaped self-care practices among home-quarantined individuals with COVID-19 during the peak of the pandemic.

METHODS: This study used convenience and snowball sampling whereby a total of 30 semi-structured telephone interviews were conducted between March and April 2022. Inductive content analysis was used to analyze the data.

RESULTS: Factors reported at the intrapersonal level included socioeconomic status and housing conditions, information and knowledge about COVID-19, long COVID, and psychological adjustments brought about by home quarantine. Factors identified at the interpersonal level included caregiving responsibilities, family relationships, and social support.

CONCLUSIONS: Findings from this study identified a combination of intra and interpersonal level factors influenced an individual's self-care practices as a result of pandemic-induced quarantine. It was particularly concerning for those individuals in socially and economically deprived groups, where access to services was challenging. This study also raised awareness of the ineffectual and insufficient knowledge individuals held of self-medication and overall COVID-19 management. A key recommendation is developing family-based resilience programmes to support and empower vulnerable families to better cope with the realities of self-quarantine.}, } @article {pmid36090973, year = {2022}, author = {García-Abellán, J and Fernández, M and Padilla, S and García, JA and Agulló, V and Lozano, V and Ena, N and García-Sánchez, L and Gutiérrez, F and Masiá, M}, title = {Immunologic phenotype of patients with long-COVID syndrome of 1-year duration.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {920627}, pmid = {36090973}, issn = {1664-3224}, mesh = {*COVID-19/complications ; Female ; Humans ; Inflammation ; Longitudinal Studies ; Phenotype ; Prospective Studies ; SARS-CoV-2 ; Viral Envelope Proteins ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration.

METHODS: Prospective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed.

RESULTS: Of 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98; 95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03-0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months.

CONCLUSION: Patients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.}, } @article {pmid36090762, year = {2022}, author = {Abraham, S and Manohar, SA and Patel, R and Saji, AM and Dani, SS and Ganatra, S}, title = {Strategies for Cardio-Oncology Care During the COVID-19 Pandemic.}, journal = {Current treatment options in cardiovascular medicine}, volume = {24}, number = {8}, pages = {137-153}, pmid = {36090762}, issn = {1092-8464}, abstract = {PURPOSE OF REVIEW: The COVID-19 pandemic has disrupted healthcare and has disproportionately affected the marginalized populations. Patients with cancer and cardiovascular disease (cardio-oncology population) are uniquely affected. In this review, we explore the current data on COVID-19 vulnerability and outcomes in these patients and discuss strategies for cardio-oncology care with a focus on healthcare innovation, health equity, and inclusion.

RECENT FINDINGS: The growing evidence suggest increased morbidity and mortality from COVID-19 in patients with comorbid cancer and cardiovascular disease. Additionally, de novo cardiovascular complications such as myocarditis, myocardial infarction, arrhythmia, heart failure, and thromboembolic events have increasingly emerged, possibly due to an accentuated host immune response and cytokine release syndrome.

SUMMARY: Patient-centric policies are helpful for cardio-oncology surveillance like remote monitoring, increased use of biomarker-based surveillance, imaging modalities like CT scan, and point-of-care ultrasound to minimize the exposure for high-risk patients. Abundant prior experience in cancer therapy scaffolded the repurposed use of corticosteroids, IL-6 inhibitors, and Janus kinase inhibitors in the treatment of COVID-19 infection. COVID-19 vaccine timing and dose frequency present a challenge due to overlapping toxicities and immune cell depletion in patients receiving cancer therapies. The SARS-CoV-2 pandemic laid bare social and ethnic disparities in healthcare but also steered in innovation to combat problems of patient outreach, particularly with virtual care. In the recovery phase, the backlog in cardio-oncology care, interplay of cancer therapy-related side effects, and long COVID-19 syndrome are crucial issues to address.}, } @article {pmid36090156, year = {2022}, author = {Rao, P and Peritz, DC and Systrom, D and Lewine, K and Cornwell, WK and Hsu, JJ}, title = {Orthostatic and Exercise Intolerance in Recreational and Competitive Athletes With Long COVID.}, journal = {JACC. Case reports}, volume = {4}, number = {17}, pages = {1119-1123}, pmid = {36090156}, issn = {2666-0849}, support = {T32 HL125232/HL/NHLBI NIH HHS/United States ; }, abstract = {Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC) infection is particularly concerning to athletes who place a high premium on cardiovascular performance and competition. This initial case series shows the overlap between PASC and orthostatic intolerance in athletes, reveals the diagnostic challenges, and highlights the role of graded exercise training in this population. (Level of Difficulty: Advanced.).}, } @article {pmid36089700, year = {2023}, author = {Peluso, MJ and Mitchell, A and Wang, CY and Takahashi, S and Hoh, R and Tai, V and Durstenfeld, MS and Hsue, PY and Kelly, JD and Martin, JN and Wilson, MR and Greenhouse, B and Deeks, SG and DeRisi, JL and Henrich, TJ}, title = {Low Prevalence of Interferon α Autoantibodies in People Experiencing Symptoms of Post-Coronavirus Disease 2019 (COVID-19) Conditions, or Long COVID.}, journal = {The Journal of infectious diseases}, volume = {227}, number = {2}, pages = {246-250}, doi = {10.1093/infdis/jiac372}, pmid = {36089700}, issn = {1537-6613}, support = {K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI076614/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; 3R01AI141003/NH/NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Interferon-alpha ; Post-Acute COVID-19 Syndrome ; Autoantibodies ; Prevalence ; }, abstract = {Interferon (IFN)-specific autoantibodies have been implicated in severe coronavirus disease 2019 (COVID-19) and have been proposed as a potential driver of the persistent symptoms characterizing "long COVID," a type of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report that only 2 of 215 participants with convalescent SARS-CoV-2 infection tested over 394 time points, including 121 people experiencing long COVID symptoms, had detectable IFN-α2 antibodies. Both had been hospitalized during the acute phase of the infection. These data suggest that persistent anti-IFN antibodies, although a potential driver of severe COVID-19, are unlikely to contribute to long COVID symptoms in the postacute phase of the infection.}, } @article {pmid36089591, year = {2022}, author = {Gorecka, M and Jex, N and Thirunavukarasu, S and Chowdhary, A and Corrado, J and Davison, J and Tarrant, R and Poenar, AM and Sharrack, N and Parkin, A and Sivan, M and Swoboda, PP and Xue, H and Vassiliou, V and Kellman, P and Plein, S and Halpin, SJ and Simms, AD and Greenwood, JP and Levelt, E}, title = {Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case-control study.}, journal = {Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance}, volume = {24}, number = {1}, pages = {50}, pmid = {36089591}, issn = {1532-429X}, support = {MC_PC_20014/MRC_/Medical Research Council/United Kingdom ; 221690/Z/20/Z//Welcome Trust Clinical Career Development Fellowship/ ; COV0254//National Institute for Health Research/ ; }, mesh = {*COVID-19/complications ; Case-Control Studies ; Contrast Media ; Gadolinium ; Humans ; Magnetic Resonance Imaging ; *Myocarditis ; Predictive Value of Tests ; Spectrum Analysis ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy ([31]P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism.

METHODS: Prospective case-control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent [31]P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission.

RESULTS: Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics.

CONCLUSIONS: In this prospective case-control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.}, } @article {pmid36088642, year = {2023}, author = {Araújo, BTS and Barros, AEVR and Nunes, DTX and Remígio de Aguiar, MI and Mastroianni, VW and de Souza, JAF and Fernades, J and Campos, SL and Brandão, DC and Dornelas de Andrade, A}, title = {Effects of continuous aerobic training associated with resistance training on maximal and submaximal exercise tolerance, fatigue, and quality of life of patients post-COVID-19.}, journal = {Physiotherapy research international : the journal for researchers and clinicians in physical therapy}, volume = {28}, number = {1}, pages = {e1972}, pmid = {36088642}, issn = {1471-2865}, support = {//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; //Fundação de Amparo a Ciência e Tecnologia/ ; //Initiative "Fazer o Bem Faz Bem"/ ; //Observatório COVID PROPG/PROPESQI UFPE 2020/ ; }, mesh = {Adult ; Humans ; Adolescent ; Quality of Life ; Exercise Tolerance/physiology ; *Resistance Training ; *COVID-19 ; Fatigue ; }, abstract = {BACKGROUND AND PURPOSE: Dyspnea, fatigue, and reduced exercise tolerance are common in post-COVID-19 patients. In these patients, rehabilitation can improve functional capacity, reduce deconditioning after a prolonged stay in the intensive care unit, and facilitate the return to work. Thus, the present study verified the effects of cardiopulmonary rehabilitation consisting of continuous aerobic and resistance training of moderate-intensity on pulmonary function, respiratory muscle strength, maximum and submaximal tolerance to exercise, fatigue, and quality of life in post-COVID-19 patients.

METHODS: Quasi-experimental study with a protocol of 12 sessions of an outpatient intervention. Adults over 18 years of age (N = 26) with a diagnosis of COVID-19 and hospital discharge at least 15 days before the first evaluation were included. Participants performed moderate-intensity continuous aerobic and resistance training twice a week. Maximal and submaximal exercise tolerance, lung function, respiratory muscle strength, fatigue and quality of life were evaluated before and after the intervention protocol.

RESULTS: Cardiopulmonary rehabilitation improved maximal exercise tolerance, with 18.62% increase in peak oxygen consumption (VO2peak) and 29.05% in time to reach VO2 peak. VE/VCO2 slope reduced 5.21% after intervention. We also observed increased submaximal exercise tolerance (increase of 70.57 m in the 6-min walk test, p = 0.001), improved quality of life, and reduced perceived fatigue after intervention.

DISCUSSION: Patients recovered from COVID-19 can develop persistent dysfunctions in almost all organ systems and present different signs and symptoms. The complexity and variability of the damage caused by this disease can make it difficult to target rehabilitation programs, making it necessary to establish specific protocols. In this work, cardiopulmonary rehabilitation improved lung function, respiratory muscle strength, maximal and submaximal exercise tolerance, fatigue and quality of life. Continuous aerobic and resistance training of moderate intensity proved to be effective in the recovery of post-COVID-19 patients.}, } @article {pmid36087363, year = {2022}, author = {Besteher, B and Machnik, M and Troll, M and Toepffer, A and Zerekidze, A and Rocktäschel, T and Heller, C and Kikinis, Z and Brodoehl, S and Finke, K and Reuken, PA and Opel, N and Stallmach, A and Gaser, C and Walter, M}, title = {Larger gray matter volumes in neuropsychiatric long-COVID syndrome.}, journal = {Psychiatry research}, volume = {317}, number = {}, pages = {114836}, pmid = {36087363}, issn = {1872-7123}, mesh = {Humans ; *Gray Matter/diagnostic imaging ; *COVID-19/complications ; SARS-CoV-2 ; Brain/diagnostic imaging ; Magnetic Resonance Imaging ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID. To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed. Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found. GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.}, } @article {pmid36085055, year = {2022}, author = {Paul, E and Fancourt, D}, title = {Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: a longitudinal analysis of 1581 UK adults.}, journal = {BMC public health}, volume = {22}, number = {1}, pages = {1716}, pmid = {36085055}, issn = {1471-2458}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; Health Behavior ; Humans ; Risk Factors ; Self Report ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Demographic and infection-related characteristics have been identified as risk factors for long COVID, but research on the influence of health behaviours (e.g., exercise, smoking) immediately preceding the index infection is lacking. The aim of this study was to examine whether specific health behaviours in the month preceding infection with COVID-19 act as upstream risk factors for long COVID as well as well as three specific long COVID symptoms.

METHODS: One thousand five hundred eighty-one UK adults from the UCL COVID-19 Social Study and who had previously been infected with COVID-19 were analysed. Health behaviours in the month before infection were weekly exercise frequency, days of fresh air per week, sleep quality, smoking, consuming more than the number of recommended alcoholic drinks per week (> 14), and the number of mental health care behaviours (e.g., online mental health programme). Logistic regressions controlling for covariates (e.g., COVID-19 infection severity, socio-demographics, and pre-existing health conditions) examined the impact of health behaviours on long COVID and three long COVID symptoms (difficulty with mobility, cognition, and self-care).

RESULTS: In the month before infection with COVID-19, poor quality sleep increased the odds of long COVID (odds ratio [OR]: 3.53; (95% confidence interval [CI]: 2.01 to 6.21), as did average quality sleep (OR: 2.44; 95% CI: 1.44 to 4.12). Having smoked (OR: 8.39; 95% CI: 1.86 to 37.91) increased and meeting recommended weekly physical activity guidelines (3h hours) (OR: 0.05; 95% CI: 0.01 to 0.39) reduced the likelihood of difficulty with self-care (e.g., washing all over or dressing) amongst those with long COVID.

CONCLUSIONS: Results point to the importance of sleep quality for long COVID, potentially helping to explain previously demonstrated links between stress and long COVID. Results also suggest that exercise and smoking may be modifiable risk factors for preventing the development of difficulty with self-care.}, } @article {pmid36084543, year = {2022}, author = {Johnson, SU and Amundsen, OM and Johnson, MS and Hoffart, A and Halsøy, Ø and Skjerdingstad, N and Ebling, S and Ebrahimi, OV}, title = {Psychiatric symptoms in COVID-19-positive individuals in the general population: Trajectories of depression, anxiety, and insomnia.}, journal = {Psychiatry research}, volume = {317}, number = {}, pages = {114806}, pmid = {36084543}, issn = {1872-7123}, mesh = {Humans ; *COVID-19/epidemiology ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Depression/epidemiology/psychology ; Anxiety/epidemiology/psychology ; Anxiety Disorders/epidemiology/psychology ; }, abstract = {The present study investigates differences in the trajectories of anxiety, depression, and sleep problems among infected versus non-infected case-controlled individuals. Patients who tested positive for COVID-19 were selected from a representative sample in Norway (N > 10,000). In total, 126 of these individuals were infected during the project period, and this group was analyzed at T5 (May 2021). Of these positive cases, those who had completed both PHQ-9 and GAD-7 at all three measurement points were selected for longitudinal analysis using multilevel modeling. There was a significant difference at T5 between those who had tested positive for COVID-19 and matched controls. Anxiety and depression were reduced among those who tested positive, but there were no differences in trajectory when compared to matched controls. Limitations include the use of self-report measures and the assessment of symptoms at a time when strict virus mitigation protocols were in place. The present findings indicate that individuals who test positive for COVID-19 exhibit higher levels of depressive symptoms after restrictions are lifted. However, comparison of anxiety and depression symptom trajectories with matched controls reveals that both groups exhibited stable or slightly decreased symptoms.}, } @article {pmid36079751, year = {2022}, author = {Rossi, AP and Muollo, V and Dalla Valle, Z and Urbani, S and Pellegrini, M and El Ghoch, M and Mazzali, G}, title = {The Role of Obesity, Body Composition, and Nutrition in COVID-19 Pandemia: A Narrative Review.}, journal = {Nutrients}, volume = {14}, number = {17}, pages = {}, pmid = {36079751}, issn = {2072-6643}, mesh = {Body Composition ; *COVID-19/complications ; Hospitalization ; Humans ; Nutritional Status ; Obesity/complications/epidemiology/therapy ; *Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, infecting nearly 500 million people, with more than 6 million deaths recorded globally. Obesity leads people to be more vulnerable, developing worse outcomes that can require hospitalization in intensive care units (ICU). This review focused on the available findings that investigated the link between COVID-19, body composition, and nutritional status. Most studies showed that not only body fat quantity but also its distribution seems to play a crucial role in COVID-19 severity. Compared to the body mass index (BMI), visceral adipose tissue and intrathoracic fat are better predictors of COVID-19 severity and indicate the need for hospitalization in ICU and invasive mechanical ventilation. High volumes of epicardial adipose tissue and its thickness can cause an infection located in the myocardial tissue, thereby enhancing severe COVID-related myocardial damage with impairments in coronary flow reserve and thromboembolism. Other important components such as sarcopenia and intermuscular fat augment the vulnerability in contracting COVID-19 and increase mortality, inflammation, and muscle damage. Malnutrition is prevalent in this population, but a lack of knowledge remains regarding the beneficial effects aimed at optimizing nutritional status to limit catabolism and preserve muscle mass. Finally, with the increase in patients recovering from COVID-19, evaluation and treatment in those with Long COVID syndrome may become highly relevant.}, } @article {pmid36079040, year = {2022}, author = {Liang, CS and Gałecki, P and Su, KP}, title = {Unresolved Systemic Inflammation, Long COVID, and the Common Pathomechanisms of Somatic and Psychiatric Comorbidity.}, journal = {Journal of clinical medicine}, volume = {11}, number = {17}, pages = {}, pmid = {36079040}, issn = {2077-0383}, abstract = {Monoamine hypothesis is an overestimated hypothesis of major depressive disorder (MDD), and the treatments and biomarkers that target it only show modest effect in randomized controlled trials+ (RCTs) or case-control studies [...].}, } @article {pmid36078910, year = {2022}, author = {Chudzik, M and Lewek, J and Kapusta, J and Banach, M and Jankowski, P and Bielecka-Dabrowa, A}, title = {Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {17}, pages = {}, pmid = {36078910}, issn = {2077-0383}, abstract = {Background: The SARS-CoV-2 pandemic has become an enormous worldwide challenge over the last two years. However, little is still known about the risk of Long COVID (LC) in patients without comorbidities. Thus, we aimed to assess the predictors of LC in patients without comorbidities. Methods: Patients’ information, the course of the disease with symptoms, and post-COVID-19 complaints were collected within 4−12 weeks after COVID-19 recovery. Next, the patients were followed for at least 3 months. ECG, 24-h ECG monitoring, 24-h blood pressure (BP) monitoring, echocardiography, and selected biochemical tests were performed. LC was recognized based on the WHO definition. Results: We identified 701 consecutive patients, 488 of whom completed a 3-month follow-up (63% women). Comparisons were made between the LC group (n = 218) and patients without any symptoms after SARS-CoV-2 recovery (non-LC group) (n = 270). Patients with a severe course of acute-phase COVID-19 developed LC complications more often (34% vs. 19%, p < 0.0001). The persistent symptoms were observed in 45% of LC patients. The LC group also had significantly more symptoms during the acute phase of COVID-19, and they suffered significantly more often from dyspnoea (48 vs. 33%), fatigue (72 vs. 63%), chest pain (50 vs. 36%), leg muscle pain (41 vs. 32%), headache (66 vs. 52%), arthralgia (44 vs. 25%), and chills (34 vs. 25%). In LC patients, significant differences regarding sex and body mass index were observed—woman: 69% vs. 56% (p = 0.003), and BMI: 28 [24−31] vs. 26 kg/m2 [23−30] (p < 0.001), respectively. The number of symptoms in the acute phase was significantly greater in the LC group than in the control group (5 [2−8] vs. 2 [1−5], p = 0.0001). The LC group also had a higher 24-h heart rate (77 [72−83] vs. 75 [70−81], p = 0.021) at admission to the outpatient clinic. Multivariate regression analysis showed that LC patients had a higher BMI (odds ratio (OR): 1.06, 95% confidence intervals [CI]: 1.02−1.10, p = 0.007), almost twice as often had a severe course of COVID-19 (OR: 1.74, CI: 1.07−2.81, p = 0.025), and presented with joint pain in the acute phase (OR: 1.90, CI: 1.23−2.95, p = 0.004). Conclusions: A severe course of COVID-19, BMI, and arthralgia are independently associated with the risk of Long COVID in healthy individuals.}, } @article {pmid36078808, year = {2022}, author = {Buonsenso, D and Gualano, MR and Rossi, MF and Valz Gris, A and Sisti, LG and Borrelli, I and Santoro, PE and Tumminello, A and Gentili, C and Malorni, W and Valentini, P and Ricciardi, W and Moscato, U}, title = {Post-Acute COVID-19 Sequelae in a Working Population at One Year Follow-Up: A Wide Range of Impacts from an Italian Sample.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {17}, pages = {}, pmid = {36078808}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology ; Employment/psychology ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID-19 is a term used to describe the symptomatic sequelae that develop after suffering from COVID-19. Very few studies have investigated the impact of COVID-19 sequelae on employment status. The aim of this research was to characterise sequelae of COVID-19 in a population of workers who tested positive for COVID-19, with a follow-up within one year of the acute illness, and to analyse the possible association between this and changes in the workers' occupational status. In this retrospective cohort study, a questionnaire was administered to 155 workers; descriptive, univariate (chi-square tests), and multivariate (logistic regression model) analyses were carried out. The mean age was 46.48 years (SD ± 7.302); 76 participants were males (49.7%), and 33 participants reported being current smokers (21.3%). Overall, 19.0% of patients reported not feeling fully recovered at follow-up, and 13.7% reported a change in their job status after COVID-19. A change in occupational status was associated with being a smoker (OR 4.106, CI [1.406-11.990], p = 0.010); hospital stay was associated with age > 46 years in a statistically significant way (p = 0.025) and with not feeling fully recovered at follow-up (p = 0.003). A persistent worsening in anxiety was more common in women (p = 0.028). This study identifies smoking as a risk factor for workers not able to resume their job; furthermore, occupational physicians should monitor mental health more closely after COVID-19, particularly in female workers.}, } @article {pmid36075815, year = {2022}, author = {Barazzoni, R and Breda, J and Cuerda, C and Schneider, S and Deutz, NE and Wickramasinghe, K and , }, title = {COVID-19: Lessons on malnutrition, nutritional care and public health from the ESPEN-WHO Europe call for papers.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {41}, number = {12}, pages = {2858-2868}, pmid = {36075815}, issn = {1532-1983}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Humans ; *COVID-19/epidemiology ; Nutrition Assessment ; Nutritional Status ; Public Health ; Communicable Disease Control ; *Malnutrition/epidemiology/prevention & control/diagnosis ; Europe/epidemiology ; Obesity ; World Health Organization ; Post-Acute COVID-19 Syndrome ; }, abstract = {With prolonged pandemic conditions, and emerging evidence but persisting low awareness of the importance of nutritional derangements, ESPEN has promoted in close collaboration with World Health Organization-Europe a call for papers on all aspects relating COVID-19 and nutrition as well as nutritional care, in the Society Journals Clinical Nutrition and Clinical Nutrition ESPEN. Although more COVID-related papers are being submitted and continue to be evaluated, ESPEN and WHO present the current editorial to summarize the many published findings supporting major interactions between nutritional status and COVID-19. These include 1) high risk of developing the disease and high risk of severe disease in the presence of pre-existing undernutrition (malnutrition) including micronutrient deficiencies; 2) high risk of developing malnutrition during the course of COVID-19, with substantial impact on long-term sequelae and risk of long COVID; 3) persons with obesity are also prone to develop or worsen malnutrition and its negative consequences during the course of COVID-19; 4) malnutrition screening and implementation of nutritional care may improve disease outcomes; 5) social and public health determinants contribute to the interaction between nutritional status and COVID-19, including negative impact of lockdown and social limitations on nutrition quality and nutritional status. We believe the evidence supports the need to consider COVID-19 as (also) a case of malnutrition-enhanced disease and disease-related malnutrition, with added risk for persons both with and without obesity. Similarities with many other disease conditions further support recommendations to implement standard nutritional screening and care in COVID-19 patients, and they underscore the relevance of appropriate nutritional and lifestyle prevention policies to limit infection risk and mitigate the negative health impact of acute pandemic bouts.}, } @article {pmid36075330, year = {2022}, author = {Hugon, J}, title = {Author's response to the letter on the article: "Long-COVID: cognitive deficits (brain fog) and brain lesions in non-hospitalized patients".}, journal = {Presse medicale (Paris, France : 1983)}, volume = {51}, number = {2}, pages = {104137}, doi = {10.1016/j.lpm.2022.104137}, pmid = {36075330}, issn = {2213-0276}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Cognition Disorders/etiology ; *Nervous System Diseases ; Brain/diagnostic imaging ; Cognition ; }, } @article {pmid36074854, year = {2022}, author = {Marshall-Gradisnik, S and Eaton-Fitch, N}, title = {Understanding myalgic encephalomyelitis.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6611}, pages = {1150-1151}, doi = {10.1126/science.abo1261}, pmid = {36074854}, issn = {1095-9203}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/virology ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Myalgic encephalomyelitis and Long Covid have overlapping presentation.}, } @article {pmid36074833, year = {2022}, author = {Pierce, CA and Herold, KC and Herold, BC and Chou, J and Randolph, A and Kane, B and McFarland, S and Gurdasani, D and Pagel, C and Hotez, P and Cobey, S and Hensley, SE}, title = {COVID-19 and children.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6611}, pages = {1144-1149}, pmid = {36074833}, issn = {1095-9203}, support = {R01 AI134367/AI/NIAID NIH HHS/United States ; MR/S003711/2/MRC_/Medical Research Council/United Kingdom ; T32 AI007501/AI/NIAID NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; MR/S003711/1/MRC_/Medical Research Council/United Kingdom ; 75N93021C00015/AI/NIAID NIH HHS/United States ; T32 GM007288/GM/NIGMS NIH HHS/United States ; }, mesh = {Aged ; *COVID-19/complications/therapy ; Child ; Humans ; *Pandemics ; SARS-CoV-2 ; *Systemic Inflammatory Response Syndrome/therapy/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.}, } @article {pmid36074666, year = {2022}, author = {Popescu, M and Terzea, DC and Carsote, M and Ghenea, AE and Costache, A and Popescu, IAS and Biciuşcă, V and Busuioc, CJ and Ghemigian, AM}, title = {COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.}, journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie}, volume = {63}, number = {1}, pages = {39-48}, pmid = {36074666}, issn = {2066-8279}, mesh = {Adrenal Glands ; *Adrenal Insufficiency/complications ; *COVID-19/complications ; Glucocorticoids ; Hemorrhage/complications ; Humans ; Hydrocortisone ; Infarction/complications ; Necrosis/complications ; Retrospective Studies ; *Thrombosis/complications ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.}, } @article {pmid36074464, year = {2022}, author = {Mendes Paranhos, AC and Nazareth Dias, ÁR and Machado da Silva, LC and Vieira Hennemann Koury, G and de Jesus Sousa, E and Cerasi, AJ and Souza, GS and Simões Quaresma, JA and Magno Falcão, LF}, title = {Sociodemographic Characteristics and Comorbidities of Patients With Long COVID and Persistent Olfactory Dysfunction.}, journal = {JAMA network open}, volume = {5}, number = {9}, pages = {e2230637}, pmid = {36074464}, issn = {2574-3805}, mesh = {Adult ; Anosmia/epidemiology ; *COVID-19/complications/epidemiology ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; *Olfaction Disorders/epidemiology ; SARS-CoV-2 ; Smell ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Determining the characteristics, type, and severity of olfactory dysfunction in patients with long COVID is important for the prognosis and potential treatment of the affected population.

OBJECTIVE: To describe the sociodemographic and clinical features of patients with long COVID who develop persistent olfactory dysfunction.

This cross-sectional study, conducted at a rehabilitation center at a public university in the Amazon region of Brazil between September 9, 2020, and October 20, 2021, comprised 219 patients with long COVID and self-reported neurologic symptoms. Of these 219 patients, 139 received a diagnosis of chronic olfactory dysfunction, as confirmed by the Connecticut Chemosensory Clinical Research Center (CCCRC) test.

EXPOSURE: Clinical diagnosis of long COVID.

MAIN OUTCOMES AND MEASURES: Electronic case report forms were prepared for the collection of sociodemographic and clinical data. Patients' sense of smell was evaluated via a CCCRC test, and the association of olfactory dysfunction with aspects of daily life was recorded using a questionnaire.

RESULTS: Of the 219 patients included in the study, 164 (74.9%) were women, 194 (88.6%) were between 18 and 59 years of age (mean [SD] age, 43.2 [12.9] years), 206 (94.1%) had more than 9 years of education, and 115 (52.5%) had a monthly income of up to US $192.00. In the study group, 139 patients (63.5%) had some degree of olfactory dysfunction, whereas 80 patients (36.5%) had normosmia. Patients with olfactory dysfunction had a significantly longer duration of long COVID symptoms than those in the normosmia group (mean [SD], 242.7 [101.9] vs 221.0 [97.5] days; P = .01). Among patients with anosmia, there was a significant association between olfactory dysfunction and daily activities, especially in terms of impairment in hazard detection (21 of 31 patients [67.7%]), personal hygiene (21 of 31 patients [67.7%]), and food intake (21 of 31 patients [67.7%]). Univariable logistic regression analyses found that ageusia symptoms were associated with the occurrence of olfactory dysfunction (odds ratio [OR], 11.14 [95% CI, 4.76-26.07]; P < .001), whereas headache (OR, 0.41 [95% CI, 0.22-0.76]; P < .001) and sleep disorders (OR, 0.48 [95% CI, 0.26-0.92]; P = .02) showed an inverse association with the occurrence of olfactory dysfunction.

CONCLUSIONS AND RELEVANCE: Olfactory dysfunction is one of the most important long-term neurologic symptoms of COVID-19, with the highest prevalence seen among women, adults, and outpatients. Patients with olfactory dysfunction may experience persistent severe hyposmia or anosmia more than 1 year from the onset of symptoms, suggesting the possibility of the condition becoming a permanent sequela.}, } @article {pmid36072173, year = {2022}, author = {Dale, L}, title = {Neurological Complications of COVID-19: A Review of the Literature.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e27633}, pmid = {36072173}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) has caused the most unprecedented health crisis since the 1918 H1N1 pandemic. Whilst COVID-19 is traditionally considered to be a respiratory disease, it is important to understand that this virus has the potential to disseminate throughout the body causing multi-organ failure. Both peripheral and central neurological systems have been shown to be greatly affected. This review aims to look at the available literature published on COVID-19 and summarize the main neurological complications seen so far.}, } @article {pmid36071155, year = {2022}, author = {Mantovani, A and Morrone, MC and Patrono, C and Santoro, MG and Schiaffino, S and Remuzzi, G and Bussolati, G and , }, title = {Long Covid: where we stand and challenges ahead.}, journal = {Cell death and differentiation}, volume = {29}, number = {10}, pages = {1891-1900}, pmid = {36071155}, issn = {1476-5403}, mesh = {*COVID-19/complications ; Humans ; Lung/pathology ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.}, } @article {pmid36070309, year = {2022}, author = {Jansen, EB and Orvold, SN and Swan, CL and Yourkowski, A and Thivierge, BM and Francis, ME and Ge, A and Rioux, M and Darbellay, J and Howland, JG and Kelvin, AA}, title = {After the virus has cleared-Can preclinical models be employed for Long COVID research?.}, journal = {PLoS pathogens}, volume = {18}, number = {9}, pages = {e1010741}, pmid = {36070309}, issn = {1553-7374}, support = {OV5-170349//CIHR/Canada ; VRI-172779//CIHR/Canada ; OV2- 170357//CIHR/Canada ; }, mesh = {Animals ; *COVID-19/complications ; Cricetinae ; Ferrets ; Humans ; Mesocricetus ; Mice ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well as debilitating multiorgan dysfunction that persists after the initial viral phase has resolved. Long COVID or Post-Acute Sequelae of COVID-19 (PASC) is manifested by a variety of symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% and 75% of recovering COVID-19 patients. However, little is known about the mechanisms causing Long COVID and there are no widely accepted treatments or therapeutics. After introducing the clinical aspects of acute COVID-19 and Long COVID in humans, we summarize the work in animals (mice, Syrian hamsters, ferrets, and nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, and multiorgan involvement are explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) are highlighted for insight into possible long-term disease characteristics. Finally, we discuss how the models can be leveraged for treatment evaluation, including pharmacological agents that are currently in human clinical trials for treating Long COVID. The establishment of a recognized Long COVID preclinical model representing the human condition would allow the identification of mechanisms causing disease as well as serve as a vehicle for evaluating potential therapeutics.}, } @article {pmid36069885, year = {2022}, author = {Wang, S and Quan, L and Chavarro, JE and Slopen, N and Kubzansky, LD and Koenen, KC and Kang, JH and Weisskopf, MG and Branch-Elliman, W and Roberts, AL}, title = {Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions.}, journal = {JAMA psychiatry}, volume = {79}, number = {11}, pages = {1081-1091}, pmid = {36069885}, issn = {2168-6238}, support = {U01 HL145386/HL/NHLBI NIH HHS/United States ; R24 ES028521/ES/NIEHS NIH HHS/United States ; R01 HD094725/HD/NICHD NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; R01 HD057368/HD/NICHD NIH HHS/United States ; }, mesh = {Female ; Humans ; Middle Aged ; Male ; *COVID-19/epidemiology ; Loneliness/psychology ; SARS-CoV-2 ; Depression/diagnosis ; Prospective Studies ; Anxiety/psychology ; Stress, Psychological/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Few risk factors for long-lasting (≥4 weeks) COVID-19 symptoms have been identified.

OBJECTIVE: To determine whether high levels of psychological distress before SARS-CoV-2 infection, characterized by depression, anxiety, worry, perceived stress, and loneliness, are prospectively associated with increased risk of developing post-COVID-19 conditions (sometimes called long COVID).

This prospective cohort study used data from 3 large ongoing, predominantly female cohorts: Nurses' Health Study II, Nurses' Health Study 3, and the Growing Up Today Study. Between April 2020 and November 2021, participants were followed up with periodic surveys. Participants were included if they reported no current or prior SARS-CoV-2 infection at the April 2020 baseline survey when distress was assessed and returned 1 or more follow-up questionnaires.

EXPOSURES: Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at study baseline early in the pandemic, before SARS-CoV-2 infection, using validated questionnaires.

MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection was self-reported during each of 6 monthly and then quarterly follow-up questionnaires. COVID-19-related symptoms lasting 4 weeks or longer and daily life impairment due to these symptoms were self-reported on the final questionnaire, 1 year after baseline.

RESULTS: Of 54 960 participants, 38.0% (n = 20 902) were active health care workers, and 96.6% (n = 53 107) were female; the mean (SD) age was 57.5 (13.8) years. Six percent (3193 participants) reported a positive SARS-CoV-2 test result during follow-up (1-47 weeks after baseline). Among these, probable depression (risk ratio [RR], 1.32; 95% CI = 1.12-1.55), probable anxiety (RR = 1.42; 95% CI, 1.23-1.65), worry about COVID-19 (RR, 1.37; 95% CI, 1.17-1.61), perceived stress (highest vs lowest quartile: RR, 1.46; 95% CI, 1.18-1.81), and loneliness (RR, 1.32; 95% CI, 1.08-1.61) were each associated with post-COVID-19 conditions (1403 cases) in generalized estimating equation models adjusted for sociodemographic factors, health behaviors, and comorbidities. Participants with 2 or more types of distress prior to infection were at nearly 50% increased risk for post-COVID-19 conditions (RR, 1.49; 95% CI, 1.23-1.80). All types of distress were associated with increased risk of daily life impairment (783 cases) among individuals with post-COVID-19 conditions (RR range, 1.15-1.51).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that preinfection psychological distress may be a risk factor for post-COVID-19 conditions in individuals with SARS-CoV-2 infection. Future work should examine the biobehavioral mechanism linking psychological distress with persistent postinfection symptoms.}, } @article {pmid36069846, year = {2022}, author = {Matharaarachchi, S and Domaratzki, M and Katz, A and Muthukumarana, S}, title = {Discovering Long COVID Symptom Patterns: Association Rule Mining and Sentiment Analysis in Social Media Tweets.}, journal = {JMIR formative research}, volume = {6}, number = {9}, pages = {e37984}, pmid = {36069846}, issn = {2561-326X}, abstract = {BACKGROUND: The COVID-19 pandemic is a substantial public health crisis that negatively affects human health and well-being. As a result of being infected with the coronavirus, patients can experience long-term health effects called long COVID syndrome. Multiple symptoms characterize this syndrome, and it is crucial to identify these symptoms as they may negatively impact patients' day-to-day lives. Breathlessness, fatigue, and brain fog are the 3 most common continuing and debilitating symptoms that patients with long COVID have reported, often months after the onset of COVID-19.

OBJECTIVE: This study aimed to understand the patterns and behavior of long COVID symptoms reported by patients on the Twitter social media platform, which is vital to improving our understanding of long COVID.

METHODS: Long COVID-related Twitter data were collected from May 1, 2020, to December 31, 2021. We used association rule mining techniques to identify frequent symptoms and establish relationships between symptoms among patients with long COVID in Twitter social media discussions. The highest confidence level-based detection was used to determine the most significant rules with 10% minimum confidence and 0.01% minimum support with a positive lift.

RESULTS: Among the 30,327 tweets included in our study, the most frequent symptoms were brain fog (n=7812, 25.8%), fatigue (n=5284, 17.4%), breathing/lung issues (n=4750, 15.7%), heart issues (n=2900, 9.6%), flu symptoms (n=2824, 9.3%), depression (n=2256, 7.4%) and general pains (n=1786, 5.9%). Loss of smell and taste, cold, cough, chest pain, fever, headache, and arm pain emerged in 1.6% (n=474) to 5.3% (n=1616) of patients with long COVID. Furthermore, the highest confidence level-based detection successfully demonstrates the potential of association analysis and the Apriori algorithm to establish patterns to explore 57 meaningful relationship rules among long COVID symptoms. The strongest relationship revealed that patients with lung/breathing problems and loss of taste are likely to have a loss of smell with 77% confidence.

CONCLUSIONS: There are very active social media discussions that could support the growing understanding of COVID-19 and its long-term impact. These discussions enable a potential field of research to analyze the behavior of long COVID syndrome. Exploratory data analysis using natural language processing methods revealed the symptoms and medical conditions related to long COVID discussions on the Twitter social media platform. Using Apriori algorithm-based association rules, we determined interesting and meaningful relationships between symptoms.}, } @article {pmid36068887, year = {2022}, author = {Noordzij, M}, title = {[Not Available].}, journal = {Tijdschrift voor verzorgenden}, volume = {54}, number = {5}, pages = {10-12}, doi = {10.1007/s41183-022-1304-4}, pmid = {36068887}, issn = {0921-5832}, } @article {pmid36066294, year = {2022}, author = {Mangion, K and Berry, C}, title = {Multisystem involvement in COVID-19: what have we learnt?.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {83}, number = {8}, pages = {1-5}, doi = {10.12968/hmed.2022.0290}, pmid = {36066294}, issn = {1750-8460}, mesh = {*COVID-19/complications ; Heart ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 illness trajectory involves persistent cardio-renal inflammation, activation of the haemostatic pathway and lung involvement. Results of a study carried out by the authors' team demonstrate a link between post-COVID-19 syndrome (people who have long COVID) and multisystem disease, which partly explains the lingering impairments in patient-reported health-related quality of life, physical function and psychological wellbeing after COVID-19. This article discusses what hospital physicians need to be aware of when considering the likelihood of myocarditis in patients with post-COVID-19 syndrome and the implications in the longer term.}, } @article {pmid36065103, year = {2022}, author = {Bellanti, JA}, title = {The long COVID syndrome: A conundrum for the allergist/immunologist.}, journal = {Allergy and asthma proceedings}, volume = {43}, number = {5}, pages = {368-374}, pmid = {36065103}, issn = {1539-6304}, mesh = {Allergists ; *COVID-19/complications/epidemiology ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: The long coronavirus disease 2019 (COVID-19) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. Objective: The purpose of this report was to examine the current body of evidence that deals with the relationship of COVID-19 infection with the long COVID syndrome to define the possible immunologic mechanisms involved in the pathogenesis of long COVID and to describe potential strategies for the diagnosis and clinical management of the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as long COVID, post-COVID-19 condition, pathogenesis of long COVID, management of the long COVID syndrome. Results: The post-COVID conditions, a more recent and less anxiety-inducing term for the patient than long COVID or "long haul," is an umbrella term for a wide range of physical and mental health symptoms similar to those seen in patients with the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), experienced by some patients and are present ≥ 4 weeks after SARS-CoV-2 infection. Although the precise reason why long COVID develops is unknown, one of the major causes is thought to be related to chronic inflammation with overproduction of inflammatory cytokines responsible for the symptoms of the disorder. Conclusion: Long COVID is a growing burden for millions of patients, health-care providers, and global health-care systems, and is a particular challenge for the allergist/immunologist. Many survivors of COVID-19 struggle with multiple symptoms, increased disability, reduced function, and poor quality of life. The allergist/immunologist can assist the total health-care team's efforts in providing a comprehensive and coordinated approach to the management of these patients by promoting comprehensive vaccination and rehabilitation and social services that focus on improving physical, mental, and social well-being, and by establishing partnerships with specialists and other health-care professionals who can provide behavioral, lifestyle, and integrative approaches that may have much to offer in helping patients cope with their symptoms.}, } @article {pmid36062113, year = {2022}, author = {Floridia, M and Grassi, T and Giuliano, M and Tiple, D and Pricci, F and Villa, M and Silenzi, A and Onder, G}, title = {Characteristics of Long-COVID care centers in Italy. A national survey of 124 clinical sites.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {975527}, pmid = {36062113}, issn = {2296-2565}, mesh = {*COVID-19/complications/epidemiology ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; *Telemedicine/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Despite the growing clinical relevance of Long-COVID, there is minimal information available on the organizational response of health services to this condition.

METHODS: A national online survey of centers providing assistance for Long-COVID was implemented. Information collected included date of start of activity, target population, mode of assistance and of referral, type and number of specialists available, diagnostic and instrumental tests, use of telemedicine and of specific questionnaires.

RESULTS: Between February and May 2022, 124 centers completed the survey. Half of them were situated in northern Italy. Most (88.9%) provided assistance through either outpatient visits or day hospital services. Eleven (8.9%) assisted pediatric patients. Access to centers included scheduled visits for previously hospitalized patients (67.7%), referral from primary care (62.1%), from other specialists (46.8%), and, less commonly, from other services. Almost half of the centers (46.3%) started their activity early in the pandemics (March-September 2020). Almost all (93.5%) communicated with primary care physicians, and 21.8% used telemedicine tools. The mean number of patients followed was 40 per month (median 20, IQR 10-40). In most cases, the center coordinator was a specialist in respiratory diseases (30.6%), infectious diseases (28.2%), or internal medicine (25.0%). At least half of the centers had specialistic support in cardiology, respiratory diseases, radiology, infectious diseases, neurology and psychology, but roughly one quarter of centers had just only one (14.5%) or two (9.7%) specialists available. The clinical assessment was usually supported by a wide range of laboratory and instrumental diagnostics and by multidimensional evaluations.

CONCLUSIONS: Most of the centers had an articulate and multidisciplinary approach to diagnosis and care of Long-COVID. However, a minority of centers provided only single or dual specialistic support. These findings may be of help in defining common standards, interventions and guidelines that can reduce gaps and heterogeneity in assistance to patients with Long-COVID.}, } @article {pmid36062008, year = {2022}, author = {Guido, CA and Lucidi, F and Midulla, F and Zicari, AM and Bove, E and Avenoso, F and Amedeo, I and Mancino, E and Nenna, R and De Castro, G and Capponi, M and Cinicola, BL and Brindisi, G and Grisoni, F and Murciano, M and Spalice, A and , }, title = {Neurological and psychological effects of long COVID in a young population: A cross-sectional study.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {925144}, pmid = {36062008}, issn = {1664-2295}, abstract = {AIM: We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3-5 months after infection have psychological consequences that interfere with their adaptive functioning.

METHOD: We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3-5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease.

RESULTS: At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3-5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5-5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6-18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID.

CONCLUSIONS: These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents.}, } @article {pmid36059441, year = {2022}, author = {Brehm, J and Spaeth, A and Dreßler, L and Masetto, T and Dannenberg, R and Peter, C and Grimmler, M}, title = {SARS-CoV-2 antibody progression and neutralizing potential in mild symptomatic COVID-19 patients - a comparative long term post-infection study.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {915338}, pmid = {36059441}, issn = {1664-3224}, mesh = {Antibodies, Viral ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Since December 2019, SARS-CoV-2 has been keeping the world in suspense. Rapid tests, molecular diagnosis of acute infections, and vaccination campaigns with vaccines are building blocks of strategic pandemic control worldwide. For laboratory diagnostics, the quantification of the antibody titer of convalescents and vaccinated patients is thus increasingly coming to the fore.

METHODS: Here we present an evaluation on the comparability of five serological tests on a cohort of 13 patients with mild COVID-19 disease. Also participants who were vaccinated after recovery were included in this study. All common immune methods (ELISA, CLIA, PETIA) and SARS-CoV-2 specific antigens (N-, S1- and RBD-) were specifically tracked and directly compared for up to 455 days. The titer of recovered participants was also set to the degree of symptoms during infection and the occurrence of Long-COVID. In addition, relative comparability of different serological tests, all standardized to WHO, was set in reference to the neutralizing potential of the corresponding participants.

FINDINGS: The individual immune responses over 455 days after a mild SARS-CoV-2 infection remain stable, in contrast to vaccinated participants. All sero-tests reveal comparable performance and dynamics during the study and compared well to a surrogate neutralization test.

CONCLUSION: The information presented here will help clinicians in the daily laboratory work in the selection and evaluation of different serological tests offered. The data also will support in respect of a sero-test-based neutralization cutoff.}, } @article {pmid36058345, year = {2022}, author = {Tanni, SE and Tonon, CR and Gatto, M and Mota, GAF and Okoshi, MP}, title = {Post-COVID-19 syndrome: Cardiovascular manifestations.}, journal = {International journal of cardiology}, volume = {369}, number = {}, pages = {80-81}, pmid = {36058345}, issn = {1874-1754}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36056372, year = {2022}, author = {Hatcher, S and Werier, J and Edgar, NE and Booth, J and Cameron, DWJ and Corrales-Medina, V and Corsi, D and Cowan, J and Giguère, P and Kaluzienski, M and Marshall, S and Mestre, T and Mulligan, B and Orpana, H and Pontefract, A and Stafford, D and Thavorn, K and Trudel, G}, title = {Enhancing COVID Rehabilitation with Technology (ECORT): protocol for an open-label, single-site randomized controlled trial evaluating the effectiveness of electronic case management for individuals with persistent COVID-19 symptoms.}, journal = {Trials}, volume = {23}, number = {1}, pages = {728}, pmid = {36056372}, issn = {1745-6215}, support = {466900/CAPMC/CIHR/Canada ; }, mesh = {Antiviral Agents/adverse effects ; *COVID-19/complications ; Case Management ; Electronics ; Fatigue/chemically induced ; Humans ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Technology ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: As of May 2022, Ontario has seen more than 1.3 million cases of COVID-19. While the majority of individuals will recover from infection within 4 weeks, a significant subset experience persistent and often debilitating symptoms, known as "post-COVID syndrome" or "Long COVID." Those with Long COVID experience a wide array of symptoms, with variable severity, including fatigue, cognitive impairment, and shortness of breath. Further, the prevalence and duration of Long COVID is not clear, nor is there evidence on the best course of rehabilitation for individuals to return to their desired level of function. Previous work with chronic conditions has suggested that the addition of electronic case management (ECM) may help to improve outcomes. These platforms provide enhanced connection with care providers, detailed symptom tracking and goal setting, and access to relevant resources. In this study, our primary aim is to determine if the addition of ECM with health coaching improves Long COVID outcomes at 3 months compared to health coaching alone.

METHODS: The trial is an open-label, single-site, randomized controlled trial of ECM with health coaching (ECM+) compared to health coaching alone (HC). Both groups will continue to receive usual care. Participants will be randomized equally to receive health coaching (± ECM) for a period of 8 weeks and a 12-week follow-up. Our primary outcome is the WHO Disability Assessment Scale (WHODAS), 36-item self-report total score. Participants will also complete measures of cognition, fatigue, breathlessness, and mental health. Participants and care providers will be asked to complete a brief qualitative interview at the end of the study to evaluate acceptability and implementation of the intervention.

DISCUSSION: There is currently little evidence about the optimal treatment of Long COVID patients or the use of digital health platforms in this population. The results of this trial could result in rapid, scalable, and personalized care for people with Long COVID which will decrease morbidity after an acute infection. Results from this study will also inform decision making in Long COVID and treatment guidelines at provincial and national levels.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05019963. Registered on 25 August 2021.}, } @article {pmid36605410, year = {2021}, author = {Oduro-Mensah, D and Oduro-Mensah, E and Quashie, P and Awandare, G and Okine, L}, title = {Explaining the unexpected COVID-19 trends and potential impact across Africa.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {1177}, pmid = {36605410}, issn = {2046-1402}, support = {MR/P028071/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Africa/epidemiology ; Inflammation ; Immunity, Innate ; }, abstract = {Official COVID-19 case counts and mortality rates across Africa are lower than had been anticipated. Research reports, however, indicate far higher exposure rates than the official counts in some countries. Particularly in Western and Central Africa, where mortality rates are disproportionately lower than the rest of the continent, this occurrence may be due to immune response adaptations resulting from (1) frequent exposure to certain pro-inflammatory pathogens, and (2) a prevalence of low-grade inflammation coupled with peculiar modifications to the immune response based on one's immunobiography. We suggest that the two factors lead to a situation where post infection, there is a rapid ramp-up of innate immune responses, enough to induce effective defense and protection against plethora pathogens. Alongside current efforts at procuring and distributing vaccines, we draw attention to the need for work towards appreciating the impact of the apparently widespread, asymptomatic SARS-CoV-2 infections on Africa's populations vis a vis systemic inflammation status and long-term consequences for public health.}, } @article {pmid36054105, year = {2022}, author = {do Prado, CB and Emerick, GS and Cevolani Pires, LB and Salaroli, LB}, title = {Impact of long-term COVID on workers: A systematic review protocol.}, journal = {PloS one}, volume = {17}, number = {9}, pages = {e0265705}, pmid = {36054105}, issn = {1932-6203}, mesh = {Activities of Daily Living ; *COVID-19/complications/epidemiology ; Humans ; *Occupational Health ; Quality of Life ; Systematic Reviews as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Part of the patients infected by COVID-19 have at least one lasting sequel of the disease and may be framed in the concept of long Covid. These sequelae can compromise the quality of life, increase dependence on other people for personal care, impair the performance of activities of daily living, thus compromising work activities and harming the health of the worker. This protocol aims to critically synthesize the scientific evidence on the effects of Covid-19 among workers and its impact on their health status and professional life.

METHOD: Searches will be performed in MEDLINE via PubMed, EMBASE, Cochrane Library Central, Web of Science, Scopus, LILACS and Epistemonikos. Included studies will be those that report the prevalence of long-term signs and symptoms in workers and/or the impact on their health status and work performance, which may be associated with Covid-19 infection. Data extraction will be conducted by 3 reviewers independently. For data synthesis, a results report will be carried out, based on the main outcome of this study.

DISCUSSION: This review will provide evidence to support health surveillance to help decision makers (i.e. healthcare providers, stakeholders and governments) regarding long-term Covid.

TRIAL REGISTRATION: PROSPERO registration number: CRD42021288120. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288120.}, } @article {pmid36053670, year = {2023}, author = {Chang, X and Ismail, NI and Rahman, A and Xu, D and Chan, RWY and Ong, SG and Ong, SB}, title = {Long COVID-19 and the Heart: Is Cardiac Mitochondria the Missing Link?.}, journal = {Antioxidants & redox signaling}, volume = {38}, number = {7-9}, pages = {599-618}, pmid = {36053670}, issn = {1557-7716}, support = {K99 HL130416/HL/NHLBI NIH HHS/United States ; R00 HL130416/HL/NHLBI NIH HHS/United States ; R01 HL148756/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology ; *Heart Diseases ; *Myocarditis/complications/therapy ; Mitochondria ; }, abstract = {Significance: Although corona virus disease 2019 (COVID-19) has now gradually been categorized as an endemic, the long-term effect of COVID-19 in causing multiorgan disorders, including a perturbed cardiovascular system, is beginning to gain attention. Nonetheless, the underlying mechanism triggering post-COVID-19 cardiovascular dysfunction remains enigmatic. Are cardiac mitochondria the key to mediating cardiac dysfunction post-severe acute respiratory syndrome coronavirus 2 (post-SARS-CoV-2) infection? Recent Advances: Cardiovascular complications post-SARS-CoV-2 infection include myocarditis, myocardial injury, microvascular injury, pericarditis, acute coronary syndrome, and arrhythmias (fast or slow). Different types of myocardial damage or reduced heart function can occur after a lung infection or lung injury. Myocardial/coronary injury or decreased cardiac function is directly associated with increased mortality after hospital discharge in patients with COVID-19. The incidence of adverse cardiovascular events increases even in recovered COVID-19 patients. Disrupted cardiac mitochondria postinfection have been postulated to lead to cardiovascular dysfunction in the COVID-19 patients. Further studies are crucial to unravel the association between SARS-CoV-2 infection, mitochondrial dysfunction, and ensuing cardiovascular disorders (CVD). Critical Issues: The relationship between COVID-19 and myocardial injury or cardiovascular dysfunction has not been elucidated. In particular, the role of the cardiac mitochondria in this association remains to be determined. Future Directions: Elucidating the cause of cardiac mitochondrial dysfunction post-SARS-CoV-2 infection may allow a deeper understanding of long COVID-19 and resulting CVD, thus providing a potential therapeutic target. Antioxid. Redox Signal. 38, 599-618.}, } @article {pmid36052466, year = {2023}, author = {Swank, Z and Senussi, Y and Manickas-Hill, Z and Yu, XG and Li, JZ and Alter, G and Walt, DR}, title = {Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {3}, pages = {e487-e490}, pmid = {36052466}, issn = {1537-6591}, support = {//NIH/ ; }, mesh = {Humans ; *Antigens, Viral/blood/immunology ; *COVID-19/blood/complications/immunology ; Disease Progression ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome/blood/diagnosis/immunology ; Biomarkers/blood ; *Spike Glycoprotein, Coronavirus/blood ; }, abstract = {The diagnosis of postacute sequelae of coronavirus disease 2019 (PASC) poses an ongoing medical challenge. To identify biomarkers associated with PASC we analyzed plasma samples collected from PASC and coronavirus disease 2019 patients to quantify viral antigens and inflammatory markers. We detect severe acute respiratory syndrome coronavirus 2 spike predominantly in PASC patients up to 12 months after diagnosis.}, } @article {pmid36051716, year = {2022}, author = {Swarnakar, R and Yadav, SL}, title = {Communicable to Non-communicable Disease Pandemic in the Making: An Urgent Call for Post-COVID-19 Preparedness.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e27453}, pmid = {36051716}, issn = {2168-8184}, abstract = {We have entered the third year of the coronavirus disease 2019 (COVID-19) pandemic. If we look back, we can see how this pandemic caused a wide spectrum of disabilities and death worldwide. Moreover, COVID-19 is notorious for affecting multiple systems of our body leading to what we call "long-COVID". Many people are still suffering from persistent symptoms of long-COVID. Apart from respiratory complications, it is causing cardiac issues, renal failure, stroke, etc. Due to such multiple complications, the rate of disability and functional impairments has increased in the past two years following the beginning of this pandemic. Thus, an infectious disease/communicable disease such as COVID-19 is indirectly leading to increased incidence of several non-communicable diseases (cardiac, renal, neurological, etc.). In this scenario, urgent preparedness in all aspects is warranted to control such a situation.}, } @article {pmid36051597, year = {2022}, author = {Löffler-Stastka, H and Pietrzak-Franger, M}, title = {COVID-19 survivors: Multi-disciplinary efforts in psychiatry and medical humanities for long-term realignment.}, journal = {World journal of psychiatry}, volume = {12}, number = {7}, pages = {995-998}, pmid = {36051597}, issn = {2220-3206}, abstract = {The coronavirus disease 2019 pandemic represents an enduring transformation in health care and education with the advancement of smart universities, telehealth, adaptive research protocols, personalized medicine, and self-controlled or artificial intelligence-controlled learning. These changes, of course, also cover mental health and long-term realignment of coronavirus disease 2019 survivors. Fatigue or anxiety, as the most prominent psychiatric "long coronavirus disease 2019" symptoms, need a theory-based and empirically-sound procedure that would help us grasp the complexity of the condition in research and treatment. Considering the systemic character of the condition, such strategies have to take the whole individual and their sociocultural context into consideration. Still, at the moment, attempts to build an integrative framework for providing meaning and understanding for the patients of how to cope with anxiety when they are confronted with empirically reduced parameters (e.g., severe acute respiratory syndrome coronavirus type 2) or biomarkers (e.g., the FK506 binding protein 5) are rare. In this context, multidisciplinary efforts are necessary. We therefore join in a plea for an establishment of 'translational medical humanities' that would allow a more straightforward intervention of humanities (e.g., the importance of the therapist variable, continuity, the social environment, etc) into the disciplinary, medial, political, and popular cultural debates around health, health-care provision, research (e.g., computer scientists for simulation studies), and wellbeing.}, } @article {pmid36051247, year = {2022}, author = {Notarte, KI and Catahay, JA and Velasco, JV and Pastrana, A and Ver, AT and Pangilinan, FC and Peligro, PJ and Casimiro, M and Guerrero, JJ and Gellaco, MML and Lippi, G and Henry, BM and Fernández-de-Las-Peñas, C}, title = {Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review.}, journal = {EClinicalMedicine}, volume = {53}, number = {}, pages = {101624}, pmid = {36051247}, issn = {2589-5370}, abstract = {BACKGROUND: Although COVID-19 vaccination decreases the risk of severe illness, it is unclear whether vaccine administration may impact the prevalence of long-COVID. The aim of this systematic review is to investigate the association between COVID-19 vaccination and long-COVID symptomatology.

METHODS: MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were searched up to June 20, 2022. Peer-reviewed studies or preprints monitoring multiple symptoms appearing after acute SARS-CoV-2 infection either before or after COVID-19 vaccination collected by personal, telephone or electronic interviews were included. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale.

FINDINGS: From 2584 studies identified, 11 peer-reviewed studies and six preprints were included. The methodological quality of 82% (n=14/17) studies was high. Six studies (n=17,256,654 individuals) investigated the impact of vaccines before acute SARS-CoV-2 infection (vaccine-infection-long-COVID design). Overall, vaccination was associated with reduced risks or odds of long-COVID, with preliminary evidence suggesting that two doses are more effective than one dose. Eleven studies (n=36,736 COVID-19 survivors) investigated changes in long-COVID symptoms after vaccination (infection-long-COVID-vaccine design). Seven articles showed an improvement in long-COVID symptoms at least one dose post-vaccination, while four studies reported no change or worsening in long-COVID symptoms after vaccination.

INTERPRETATION: Low level of evidence (grade III, case-controls, cohort studies) suggests that vaccination before SARS-CoV-2 infection could reduce the risk of subsequent long-COVID. The impact of vaccination in people with existing long-COVID symptoms is still controversial, with some data showing changes in symptoms and others did not. These assumptions are limited to those vaccines used in the studies.

FUNDING: The LONG-COVID-EXP-CM study supported by a grant of Comunidad de Madrid.}, } @article {pmid36048910, year = {2022}, author = {Shaffer, L}, title = {Lots of long COVID treatment leads, but few are proven.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {36}, pages = {e2213524119}, pmid = {36048910}, issn = {1091-6490}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, } @article {pmid36046290, year = {2022}, author = {Uniyal, N and Sethi, Y and Sharma, PC and Sayana, A and Jeet, N and Agarwal, A and Rawat, V}, title = {Post-COVID Syndrome and Severity of COVID-19: A Cross-Sectional Epidemiological Evaluation From North India.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e27345}, pmid = {36046290}, issn = {2168-8184}, abstract = {Background COVID-19 has now lasted for more than two years as a pandemic and has had enduring effects on the health of people as the post-COVID syndrome. Recent literature has shown the long-term effects of COVID-19 on various organ systems, including but not limited to respiratory, cardiovascular, neurological, musculoskeletal, and gastrointestinal systems. Methods and objectives We aimed to estimate the prevalence of post-acute COVID symptoms in a tertiary care center in northern India; observe the effects of the demographic profile of age, BMI, gender, and presence of comorbidities on the persistence of post-COVID syndrome, and explore any correlation between the severity of COVID-19 disease and the persistence of post-COVID symptoms. We designed a survey containing structured questions evaluating post-COVID symptoms beyond three weeks (post-acute COVID phase), six weeks (post-COVID phase), and 12 weeks of acute illness. It was administered online. Results Prevalence of post-COVID symptoms both after three and six weeks was reported to be 16.67% and 7.37%, respectively. The most common symptoms to persist were musculoskeletal symptoms (fatigue), followed by upper respiratory symptoms. Disease severity (p<0.05), BMI (p<0.05), and comorbidities were seen to affect post-COVID symptoms significantly, whereas gender and age of the patient had no significant effect. Disease severity significantly affected the persistence of post-COVID symptoms up to 12 weeks; however, this effect does not hold true in long COVID haulers. Also, the risk of developing persistent post-acute COVID symptoms was more in moderate to severe disease than in mild disease. Conclusion The pandemic might be close to over, but it is not out of our lives yet, and the persistence of post-COVID symptoms is exigent.}, } @article {pmid36046159, year = {2022}, author = {Tavares-Júnior, JWL and Oliveira, DN and da Silva, JBS and Feitosa, WLQ and Sousa, AVM and Cunha, LCV and Gaspar, SB and Gomes, CMP and de Oliveira, LLB and Moreira-Nunes, CA and Montenegro, RC and Sobreira-Neto, MA and Braga-Neto, P}, title = {Long-covid cognitive impairment: Cognitive assessment and apolipoprotein E (APOE) genotyping correlation in a Brazilian cohort.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {947583}, pmid = {36046159}, issn = {1664-0640}, abstract = {INTRODUCTION: Few studies have objectively evaluated cognitive deficits after the acute phase of COVID-19 disease. Moreover, the role of apolipoprotein E (APOE) genotypes in cognitive decline in patients with COVID-19 has not been evaluated yet.

METHODS: This cross-sectional study was conducted in confirmed cases of COVID-19 patients with neurological symptoms that persisted for more than 3 months from the onset. We determined APOE genotypes.

RESULTS: The final sample consisted of 141 patients. The most frequent APOE genotype was E3/E3 (N = 95; 67.3%). In total, 93 patients (65.9%) had memory impairment symptoms as the main complaint, objectively confirmed through screening tests in 25 patients (17.7%). Patients with cognitive impairment had a lower frequency of anosmia than the normal and subjective cognitive decline (SCD) groups (p = 0.005). In addition, depression was recurrent in the cognitive impairment group and the SCD group (p = 0.046). Cognitive impairment was significantly more frequent in hospitalized patients and those with a lower education level. Cognitive status was not associated with APOE genotypes.

DISCUSSION: Hospitalized patients had more severe infection with a greater possibility of systemic complications, greater inflammatory response, and prolonged hospitalization, which could impact cognitive performance. Cognitive impairment in patients with COVID-19 does not necessarily involve specific APOE polymorphisms. However, psychiatric disorders may also be responsible for cognitive complaints. Cognitive complaints are frequent in patients with COVID-19, even after the acute phase of the disease and in mild cases. Hospitalized participants and depressed patients may have a higher risk of cognitive impairment. APOE genotypes or haplotypes may not significantly play a role in COVID-19 cognitive impairment.}, } @article {pmid36043493, year = {2022}, author = {Kell, DB and Pretorius, E}, title = {The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications.}, journal = {The Biochemical journal}, volume = {479}, number = {16}, pages = {1653-1708}, pmid = {36043493}, issn = {1470-8728}, mesh = {*Arthritis, Rheumatoid/therapy ; *COVID-19/complications ; *Fatigue Syndrome, Chronic/metabolism ; Humans ; Oxidative Stress/physiology ; *Reperfusion Injury/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.}, } @article {pmid36043156, year = {2022}, author = {Sakhamuri, SM and Jankie, S and Pinto Pereira, LM}, title = {Calling on Latin America and the Caribbean countries to recognise the disability from long COVID.}, journal = {Lancet regional health. Americas}, volume = {15}, number = {}, pages = {100362}, pmid = {36043156}, issn = {2667-193X}, } @article {pmid36041287, year = {2022}, author = {Hool, LC}, title = {Elucidating the role of the L-type calcium channel in excitability and energetics in the heart: The ISHR 2020 Research Achievement Award Lecture.}, journal = {Journal of molecular and cellular cardiology}, volume = {172}, number = {}, pages = {100-108}, doi = {10.1016/j.yjmcc.2022.08.001}, pmid = {36041287}, issn = {1095-8584}, mesh = {Animals ; Humans ; Calcium/metabolism ; *Calcium Channels, L-Type/physiology ; *Cardiomyopathies/metabolism ; COVID-19 ; Diabetes Mellitus, Type 2/metabolism ; Hypertrophy/metabolism ; Myocytes, Cardiac/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiovascular disease continues to be the leading health burden worldwide and with the rising rates in obesity and type II diabetes and ongoing effects of long COVID, it is anticipated that the burden of cardiovascular morbidity and mortality will increase. Calcium is essential to cardiac excitation and contraction. The main route for Ca[2+] influx is the L-type Ca[2+] channel (Cav1.2) and embryos that are homozygous null for the Cav1.2 gene are lethal at day 14 postcoitum. Acute changes in Ca[2+] influx through the channel contribute to arrhythmia and sudden death, and chronic increases in intracellular Ca[2+] contribute to pathological hypertrophy and heart failure. We use a multidisciplinary approach to study the regulation of the channel from the molecular level through to in vivo CRISPR mutant animal models. Here we describe some examples of our work from over 2 decades studying the role of the channel under physiological and pathological conditions. Our single channel analysis of purified human Cav1.2 protein in proteoliposomes has contributed to understanding direct molecular regulation of the channel including identifying the critical serine involved in the "fight or flight" response. Using the same approach we identified the cysteine responsible for altered function during oxidative stress. Chronic activation of the L-type Ca[2+] channel during oxidative stress occurs as a result of persistent glutathionylation of the channel that contributes to the development of hypertrophy. We describe for the first time that activation of the channel alters mitochondrial function (and energetics) on a beat-to-beat basis via movement of cytoskeletal proteins. In translational studies we have used this response to "report" mitochondrial function in models of cardiomyopathy and to test efficacy of novel therapies to prevent cardiomyopathy.}, } @article {pmid36040993, year = {2022}, author = {Pal, R and Chopra, H and Awasthi, R and Bandhey, H and Nagori, A and Sethi, T}, title = {Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature With Unsupervised Word Embeddings and Machine Learning: Evidence-Based Study.}, journal = {Journal of medical Internet research}, volume = {24}, number = {11}, pages = {e34067}, pmid = {36040993}, issn = {1438-8871}, mesh = {Humans ; *COVID-19 ; Machine Learning ; Semantics ; Supervised Machine Learning ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Evidence from peer-reviewed literature is the cornerstone for designing responses to global threats such as COVID-19. In massive and rapidly growing corpuses, such as COVID-19 publications, assimilating and synthesizing information is challenging. Leveraging a robust computational pipeline that evaluates multiple aspects, such as network topological features, communities, and their temporal trends, can make this process more efficient.

OBJECTIVE: We aimed to show that new knowledge can be captured and tracked using the temporal change in the underlying unsupervised word embeddings of the literature. Further imminent themes can be predicted using machine learning on the evolving associations between words.

METHODS: Frequently occurring medical entities were extracted from the abstracts of more than 150,000 COVID-19 articles published on the World Health Organization database, collected on a monthly interval starting from February 2020. Word embeddings trained on each month's literature were used to construct networks of entities with cosine similarities as edge weights. Topological features of the subsequent month's network were forecasted based on prior patterns, and new links were predicted using supervised machine learning. Community detection and alluvial diagrams were used to track biomedical themes that evolved over the months.

RESULTS: We found that thromboembolic complications were detected as an emerging theme as early as August 2020. A shift toward the symptoms of long COVID complications was observed during March 2021, and neurological complications gained significance in June 2021. A prospective validation of the link prediction models achieved an area under the receiver operating characteristic curve of 0.87. Predictive modeling revealed predisposing conditions, symptoms, cross-infection, and neurological complications as dominant research themes in COVID-19 publications based on the patterns observed in previous months.

CONCLUSIONS: Machine learning-based prediction of emerging links can contribute toward steering research by capturing themes represented by groups of medical entities, based on patterns of semantic relationships over time.}, } @article {pmid36040960, year = {2022}, author = {Moy, FM and Hairi, NN and Lim, ERJ and Bulgiba, A}, title = {Long COVID and its associated factors among COVID survivors in the community from a middle-income country-An online cross-sectional study.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0273364}, pmid = {36040960}, issn = {1932-6203}, mesh = {Anxiety/epidemiology ; *COVID-19/complications/epidemiology ; *Coronavirus Infections/epidemiology ; Cross-Sectional Studies ; Depression/epidemiology ; Female ; Humans ; Pandemics ; *Pneumonia, Viral/epidemiology ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Patients with COVID-19 usually recover and return to normal health, however some patients may have symptoms that last for weeks or even months after recovery. This persistent state of ill health is known as Long COVID if it continues for more than three months and are not explained by an alternative diagnosis. Long Covid has been overlooked, especially in the low- and middle-income countries. Therefore, we conducted an online survey among the COVID-19 survivors in the community to explore their Long COVID symptoms, factors associated with Long COVID and how Long COVID affected their work. A total of 732 COVID-19 survivors responded, with 56% were without or with mild symptoms during their acute COVID-19 conditions. One in five COVID-19 survivors reported of experiencing Long COVID. The most commonly reported symptoms were fatigue, brain fog, depression, anxiety and insomnia. Females had 58% higher odds (95% CI: 1.02, 2.45) of experiencing Long COVID. Patients with moderate and severe levels of acute COVID-19 symptoms had OR of 3.01 (95% CI: 1.21, 7.47) and 3.62 (95% CI: 1.31, 10.03) respectively for Long COVID. Recognition of Long COVID and its associated factors is important in planning prevention, rehabilitation, clinical management to improve recovery from COVID-19.}, } @article {pmid36039714, year = {2022}, author = {Abrignani, MG and Maloberti, A and Temporelli, PL and Binaghi, G and Cesaro, A and Ciccirillo, F and Oliva, F and Gabrielli, D and Riccio, C and Gulizia, MM and Colivicchi, F}, title = {[Long COVID: nosographic aspects and clinical epidemiology].}, journal = {Giornale italiano di cardiologia (2006)}, volume = {23}, number = {9}, pages = {651-662}, doi = {10.1714/3860.38447}, pmid = {36039714}, issn = {1972-6481}, mesh = {*COVID-19/complications/epidemiology/physiopathology/psychology ; Humans ; Quality of Life ; Risk Factors ; SARS-CoV-2/pathogenicity ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Recent evidence shows that a range of persistent or new symptoms can manifest after 4-12 weeks in a subset of patients who have recovered from acute SARS-CoV-2 infection, and this condition has been coined long COVID by COVID-19 survivors among social support groups. Long COVID can affect the whole spectrum of people with COVID-19, from those with very mild acute disease to the most severe forms. Like the acute form, long COVID has multisystemic aspects. Patients can manifest with a very heterogeneous multitude of symptoms, including fatigue, post-exertional malaise, dyspnea, cognitive impairment, sleep disturbances, anxiety and depression, muscle pain, brain fog, anosmia/dysgeusia, headache, and limitation of functional capacity, which impact their quality of life. Because of the extreme clinical heterogeneity, and also due to the lack of a shared, specific definition, it is very difficult to know the real prevalence and incidence of this condition. Risk factors for developing long COVID would be female sex, initial severity, and comorbidities. Globally, with the re-emergence of new waves, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating a more thorough understanding of potential sequelae of COVID-19. This review summarizes up to date definitions and epidemiological aspects of long COVID.}, } @article {pmid36038169, year = {2022}, author = {Bulley, C and Tyagi, V and Curnow, E and Nicol, K and Salisbury, L and Stuart, K and McCormack, B and Magowan, R and Sagan, O and Dewing, J}, title = {Support after COVID-19 study: a mixed-methods cross-sectional study to develop recommendations for practice.}, journal = {BMJ open}, volume = {12}, number = {8}, pages = {e056568}, pmid = {36038169}, issn = {2044-6055}, support = {COV/QMU/20/04/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Health Personnel ; Humans ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: Objectives of study stage 1 were to: explore people's experiences of illness due to COVID-19 while feeling socially isolated or socially isolating; identify perceptions of what would support recovery; and synthesise insights into recommendations for supporting people after COVID-19. Study stage 2 objectives were to engage stakeholders in evaluating these recommendations and analyse likely influences on access to the support identified.

DESIGN: A two-stage, multimethod cross-sectional study was conducted from a postpositivist perspective. Stage 1 included an international online survey of people's experiences of illness, particularly COVID-19, in isolation (n=675 full responses). Stage 2 involved a further online survey (n=43), two tweetchats treated as large online focus groups (n=60 and n=27 people tweeting), two smaller focus groups (both n=4) and one interview (both using MS teams).

SETTING: Stage 1 had an international emphasis, although 87% of respondents were living in the UK. Stage 2 focused on the UK.

PARTICIPANTS: Anyone aged 18+ and able to complete a survey in English could participate. Stage 2 included health professionals, advocates and people with lived experience.

MAIN OUTCOME MEASURES: Descriptive data and response categories derived from open responses to the survey and the qualitative data.

RESULTS: Of those responding fully to stage 1 (mean age 44 years); 130 (19%) had experienced COVID-19 in isolation; 45 had recovered, taking a mean of 5.3 (range 1-54) weeks. 85 did not feel they had recovered; fatigue and varied 'other' symptoms were most prevalent and also had most substantial negative impacts. Our draft recommendations were highly supported by respondents to stage 2 and refined to produce final recommendations.

CONCLUSIONS: Recommendations support access to progressive intensity and specialism of support, addressing access barriers that might inadvertently increase health inequalities. Multidisciplinary collaboration and learning are crucial, including the person with COVID-19 and/or Long Covid in the planning and decision making throughout.}, } @article {pmid36035093, year = {2022}, author = {Brough, DN and Abel, S and Priddle, L}, title = {A service evaluation of a community project combining psychoeducation and mind-body complementary approaches to support those with long covid in the UK.}, journal = {European journal of integrative medicine}, volume = {55}, number = {}, pages = {102182}, pmid = {36035093}, issn = {1876-3820}, abstract = {INTRODUCTION: Post covid-19 syndrome or Long Covid has been estimated to impact 1.3 million individuals in the UK. This study evaluates the outcomes of delivering a complementary Long Covid support service using psycho-educational and mind-body approaches within a community setting.

METHODS: This study utilised quantitative methods to evaluate the outcomes of implementing a complementary approach to providing Long Covid support. The service offered a package of care including group sessions combining psychoeducation and mind-body complementary approaches and optional 1:2:1 sessions (physiotherapy and craniosacral therapy (CST)). Screening for the service and health information was obtained using the Covid-19-Yorkshire Rehabilitation Screening tool (C-19 YRS). The impact of the service was assessed using the patient reported outcome measure: Warwick Holistic Health Questionnaire (WHHQ-18), and a survey was designed for general evaluation and feedback about the service from participants.

RESULTS: 25 participants engaged with the service. The C-19YRS proved to be a useful tool to screen service users. The WHHQ-18 highlighted a positive group change (n = 16) in participants' mental, physical, emotional, and spiritual wellbeing: mean group score at the start = 33.7 (SD=12.5), mean group score at the follow up = 39.5 (SD=10.8). In the feedback from the service evaluation, participants reported that the service was useful in supporting them with their health challenges resulting from Long Covid and was delivered to the standard expected.

CONCLUSION: In conclusion the psycho-educational and mind-body complementary approaches used within this service were well received and the measures used to evaluate were suitable for a service delivered within a community setting.}, } @article {pmid36033820, year = {2022}, author = {Smith, CJ and Renshaw, P and Yurgelun-Todd, D and Sheth, C}, title = {Acute and chronic neuropsychiatric symptoms in novel coronavirus disease 2019 (COVID-19) patients: A qualitative review.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {772335}, pmid = {36033820}, issn = {2296-2565}, mesh = {Anxiety ; *COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) on March 11th, 2020. It has had unprecedented adverse effects on healthcare systems, economies, and societies globally. SARS-CoV-2 is not only a threat to physical health but has also been shown to have a severe impact on neuropsychiatric health. Many studies and case reports across countries have demonstrated insomnia, depressed mood, anxiety, post-traumatic stress disorder (PTSD), and cognitive change in COVID-19 patients during the acute phase of the infection, as well as in apparently recovered COVID-19 patients. The goal of this narrative review is to synthesize and summarize the emerging literature detailing the neuropsychiatric manifestations of COVID-19 with special emphasis on the long-term implications of COVID-19.}, } @article {pmid36032983, year = {2022}, author = {Hill, E and Mehta, H and Sharma, S and Mane, K and Xie, C and Cathey, E and Loomba, J and Russell, S and Spratt, H and DeWitt, PE and Ammar, N and Madlock-Brown, C and Brown, D and McMurry, JA and Chute, CG and Haendel, MA and Moffitt, R and Pfaff, ER and Bennett, TD and , and , }, title = {Risk Factors Associated with Post-Acute Sequelae of SARS-CoV-2 in an EHR Cohort: A National COVID Cohort Collaborative (N3C) Analysis as part of the NIH RECOVER program.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {36032983}, support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR001422/TR/NCATS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; U54 GM115371/GM/NIGMS NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UL1 TR003167/TR/NCATS NIH HHS/United States ; OT2 HL161847/HL/NHLBI NIH HHS/United States ; UL1 TR001409/TR/NCATS NIH HHS/United States ; UL1 TR001449/TR/NCATS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001433/TR/NCATS NIH HHS/United States ; K01 AG070329/AG/NIA NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR001414/TR/NCATS NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UL1 TR002645/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002366/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; U54 GM115677/GM/NIGMS NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: More than one-third of individuals experience post-acute sequelae of SARS-CoV-2 infection (PASC, which includes long-COVID).

OBJECTIVE: To identify risk factors associated with PASC/long-COVID.

DESIGN: Retrospective case-control study.

SETTING: 31 health systems in the United States from the National COVID Cohort Collaborative (N3C).

PATIENTS: 8,325 individuals with PASC (defined by the presence of the International Classification of Diseases, version 10 code U09.9 or a long-COVID clinic visit) matched to 41,625 controls within the same health system.

MEASUREMENTS: Risk factors included demographics, comorbidities, and treatment and acute characteristics related to COVID-19. Multivariable logistic regression, random forest, and XGBoost were used to determine the associations between risk factors and PASC.

RESULTS: Among 8,325 individuals with PASC, the majority were >50 years of age (56.6%), female (62.8%), and non-Hispanic White (68.6%). In logistic regression, middle-age categories (40 to 69 years; OR ranging from 2.32 to 2.58), female sex (OR 1.4, 95% CI 1.33-1.48), hospitalization associated with COVID-19 (OR 3.8, 95% CI 3.05-4.73), long (8-30 days, OR 1.69, 95% CI 1.31-2.17) or extended hospital stay (30+ days, OR 3.38, 95% CI 2.45-4.67), receipt of mechanical ventilation (OR 1.44, 95% CI 1.18-1.74), and several comorbidities including depression (OR 1.50, 95% CI 1.40-1.60), chronic lung disease (OR 1.63, 95% CI 1.53-1.74), and obesity (OR 1.23, 95% CI 1.16-1.3) were associated with increased likelihood of PASC diagnosis or care at a long-COVID clinic. Characteristics associated with a lower likelihood of PASC diagnosis or care at a long-COVID clinic included younger age (18 to 29 years), male sex, non-Hispanic Black race, and comorbidities such as substance abuse, cardiomyopathy, psychosis, and dementia. More doctors per capita in the county of residence was associated with an increased likelihood of PASC diagnosis or care at a long-COVID clinic. Our findings were consistent in sensitivity analyses using a variety of analytic techniques and approaches to select controls.

CONCLUSIONS: This national study identified important risk factors for PASC such as middle age, severe COVID-19 disease, and specific comorbidities. Further clinical and epidemiological research is needed to better understand underlying mechanisms and the potential role of vaccines and therapeutics in altering PASC course.}, } @article {pmid36032234, year = {2022}, author = {Joli, J and Buck, P and Zipfel, S and Stengel, A}, title = {Post-COVID-19 fatigue: A systematic review.}, journal = {Frontiers in psychiatry}, volume = {13}, number = {}, pages = {947973}, pmid = {36032234}, issn = {1664-0640}, abstract = {UNLABELLED: Fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. This systematic review was performed to describe symptoms, etiology, possible risk factors related to post-COVID-19 fatigue and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were used. All articles that met the inclusion criteria were analyzed for demographics, clinical data and treatment. Included were studies which focused on an adult population (18-65 years old); elderly patients and patients with chronic somatic diseases which can also cause fatigue were excluded. We identified 2,851, screened 2,193 and finally included 20 studies with moderate to high methodological quality, encompassing 5,629 participants. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of comorbidities, and a prediagnosis of depression/anxiety. Lastly, a possible autoimmune etiology was suspected. Several treatment approaches have been tested mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6-min walking test) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP). Lastly. muscle strength and physical function were improved after undergoing an 8-weeks biweekly physical therapy course including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, larger and controlled studies e.g., investigating the effect of physical and / or psychotherapy for patients with post-COVID-19 fatigue are urgently warranted.

Unique Identifier: CRD42022320676, https://www.crd.york.ac.uk/PROSPERO/.}, } @article {pmid36032086, year = {2022}, author = {Moody, R and Sonda, S and Johnston, FH and Smith, KJ and Stephens, N and McPherson, M and Flanagan, KL and Plebanski, M}, title = {Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {945021}, pmid = {36032086}, issn = {1664-3224}, mesh = {*Antibodies, Viral/immunology ; Autoantibodies/immunology ; Autoantigens ; *COVID-19/complications/immunology ; Humans ; Immunoglobulin G ; Leukocyte L1 Antigen Complex/immunology ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Autoantibodies to multiple targets are found during acute COVID-19. Whether all, or some, persist after 6 months, and their correlation with sustained anti-SARS-CoV-2 immunity, is still controversial. Herein, we measured antibodies to multiple SARS-CoV-2 antigens (Wuhan-Hu-1 nucleoprotein (NP), whole spike (S), spike subunits (S1, S2 and receptor binding domain (RBD)) and Omicron spike) and 102 human proteins with known autoimmune associations, in plasma from healthcare workers 8 months post-exposure to SARS-CoV-2 (n=31 with confirmed COVID-19 disease and n=21 uninfected controls (PCR and anti-SARS-CoV-2 negative) at baseline). IgG antibody responses to SARS-CoV-2 antigens were significantly higher in the convalescent cohort than the healthy cohort, highlighting lasting antibody responses up to 8 months post-infection. These were also shown to be cross-reactive to the Omicron variant spike protein at a similar level to lasting anti-RBD antibodies (correlation r=0.89). Individuals post COVID-19 infection recognised a common set of autoantigens, specific to this group in comparison to the healthy controls. Moreover, the long-term level of anti-Spike IgG was associated with the breadth of autoreactivity post-COVID-19. There were further moderate positive correlations between anti-SARS-CoV-2 responses and 11 specific autoantigens. The most commonly recognised autoantigens were found in the COVID-19 convalescent cohort. Although there was no overall correlation in self-reported symptom severity and anti-SARS-CoV-2 antibody levels, anti-calprotectin antibodies were associated with return to healthy normal life 8 months post infection. Calprotectin was also the most common target for autoantibodies, recognized by 22.6% of the overall convalescent cohort. Future studies may address whether, counter-intuitively, such autoantibodies may play a protective role in the pathology of long-COVID-19.}, } @article {pmid36031313, year = {2022}, author = {Cavallieri, F and Sellner, J and Zedde, M and Moro, E}, title = {Neurologic complications of coronavirus and other respiratory viral infections.}, journal = {Handbook of clinical neurology}, volume = {189}, number = {}, pages = {331-358}, pmid = {36031313}, issn = {0072-9752}, mesh = {*COVID-19/complications ; Humans ; *Nervous System Diseases ; *Peripheral Nervous System Diseases ; SARS-CoV-2 ; Seizures ; Post-Acute COVID-19 Syndrome ; }, abstract = {In humans, several respiratory viruses can have neurologic implications affecting both central and peripheral nervous system. Neurologic manifestations can be linked to viral neurotropism and/or indirect effects of the infection due to endothelitis with vascular damage and ischemia, hypercoagulation state with thrombosis and hemorrhages, systemic inflammatory response, autoimmune reactions, and other damages. Among these respiratory viruses, recent and huge attention has been given to the coronaviruses, especially the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic started in 2020. Besides the common respiratory symptoms and the lung tropism of SARS-CoV-2 (COVID-19), neurologic manifestations are not rare and often present in the severe forms of the infection. The most common acute and subacute symptoms and signs include headache, fatigue, myalgia, anosmia, ageusia, sleep disturbances, whereas clinical syndromes include mainly encephalopathy, ischemic stroke, seizures, and autoimmune peripheral neuropathies. Although the pathogenetic mechanisms of COVID-19 in the various acute neurologic manifestations are partially understood, little is known about long-term consequences of the infection. These consequences concern both the so-called long-COVID (characterized by the persistence of neurological manifestations after the resolution of the acute viral phase), and the onset of new neurological symptoms that may be linked to the previous infection.}, } @article {pmid36030555, year = {2022}, author = {Xie, J and Klemsz, MJ and Kacena, MA and Sandusky, G and Zhang, X and Kaplan, MH}, title = {Inhibition of MEK signaling prevents SARS-CoV2-induced lung damage and improves the survival of infected mice.}, journal = {Journal of medical virology}, volume = {94}, number = {12}, pages = {6097-6102}, pmid = {36030555}, issn = {1096-9071}, support = {UL1 TR002529/TR/NCATS NIH HHS/United States ; U54 DK106846/DK/NIDDK NIH HHS/United States ; /NH/NIH HHS/United States ; R01 AI057459/AI/NIAID NIH HHS/United States ; R01 AI045515/AI/NIAID NIH HHS/United States ; }, mesh = {Amphiregulin ; *COVID-19/complications ; Extracellular Signal-Regulated MAP Kinases ; Humans ; Lung ; MAP Kinase Kinase Kinases ; Mitogen-Activated Protein Kinase Kinases/genetics ; RNA, Viral ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Coronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with six million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID-19-caused death, effective medication to relieve COVID-19-associated symptoms and alleviate disease progression is still in high demand. In particular, one in three COVID-19 patients have signs of long COVID syndrome and are termed, long haulers. At present, there are no effective ways to treat long haulers. In this study, we determine the effectiveness of inhibiting mitogen-activated protein kinase (MEK) signaling in preventing SARS-CoV-2-induced lung damage in mice. We showed that phosphorylation of extracellular signal-regulated kinase, a marker for MEK activation, is high in SARS-CoV-2-infected lung tissues of mice and humans. We also showed that selumetinib, a specific inhibitor of the upstream MEK kinases, reduces cell proliferation, reduces lung damage following SARS-CoV-2 infection, and prolongs the survival of the infected mice. Selumetinib has been approved by the US Food and Drug Administration to treat cancer. Further analysis indicates that amphiregulin, an essential upstream molecule, was upregulated following SARS-CoV-2 infection. Our data suggest that MEK signaling activation represents a target for therapeutic intervention strategies against SARS-CoV-2-induced lung damage and that selumetinib may be repurposed to treat COVID-19.}, } @article {pmid36030055, year = {2022}, author = {Newhouse, A and Kritzer, MD and Eryilmaz, H and Praschan, N and Camprodon, JA and Fricchione, G and Chemali, Z}, title = {Neurocircuitry Hypothesis and Clinical Experience in Treating Neuropsychiatric Symptoms of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.}, journal = {Journal of the Academy of Consultation-Liaison Psychiatry}, volume = {63}, number = {6}, pages = {619-627}, pmid = {36030055}, issn = {2667-2960}, support = {T32 MH112485/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; SARS-CoV-2 ; *COVID-19 ; Disease Progression ; *Cognitive Dysfunction ; Memory Disorders ; }, abstract = {Persistent symptoms following COVID-19 infection have been termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. Many of these symptoms are neuropsychiatric, such as inattention, impaired memory, and executive dysfunction; these are often colloquially termed "brain fog". These symptoms are common and often persist long after the acute phase. The pattern of these deficits combined with laboratory, neuroimaging, electroencephalographic, and neuropsychological data suggest that these symptoms may be driven by direct and indirect damage to the frontal-subcortical neural networks. Here, we review this evidence, share our clinical experience at an academic medical center, and discuss potential treatment implications. While the exact etiology remains unknown, a neurocircuit-informed understanding of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection can help guide pharmacology, neuromodulation, and physical and psychological therapeutic approaches.}, } @article {pmid36028767, year = {2022}, author = {Graham, F}, title = {Daily briefing: Do tiny blood clots cause long COVID?.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-02327-1}, pmid = {36028767}, issn = {1476-4687}, } @article {pmid36028604, year = {2022}, author = {Fleischer, M and Szepanowski, F and Tovar, M and Herchert, K and Dinse, H and Schweda, A and Mausberg, AK and Holle-Lee, D and Köhrmann, M and Stögbauer, J and Jokisch, D and Jokisch, M and Deuschl, C and Skoda, EM and Teufel, M and Stettner, M and Kleinschnitz, C}, title = {Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients.}, journal = {Neurology and therapy}, volume = {11}, number = {4}, pages = {1637-1657}, pmid = {36028604}, issn = {2193-8253}, abstract = {INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome.

METHODS: A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment.

RESULTS: Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue.

CONCLUSIONS: Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.}, } @article {pmid36017003, year = {2022}, author = {Curran, CS and Kopp, JB}, title = {RAGE pathway activation and function in chronic kidney disease and COVID-19.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {970423}, pmid = {36017003}, issn = {2296-858X}, abstract = {The multi-ligand receptor for advanced glycation end-products (RAGE) and its ligands are contributing factors in autoimmunity, cancers, and infectious disease. RAGE activation is increased in chronic kidney disease (CKD) and coronavirus disease 2019 (COVID-19). CKD may increase the risk of COVID-19 severity and may also develop in the form of long COVID. RAGE is expressed in essentially all kidney cell types. Increased production of RAGE isoforms and RAGE ligands during CKD and COVID-19 promotes RAGE activity. The downstream effects include cellular dysfunction, tissue injury, fibrosis, and inflammation, which in turn contribute to a decline in kidney function, hypertension, thrombotic disorders, and cognitive impairment. In this review, we discuss the forms and mechanisms of RAGE and RAGE ligands in the kidney and COVID-19. Because various small molecules antagonize RAGE activity in animal models, targeting RAGE, its co-receptors, or its ligands may offer novel therapeutic approaches to slowing or halting progressive kidney disease, for which current therapies are often inadequate.}, } @article {pmid36016385, year = {2022}, author = {Chudzik, M and Babicki, M and Mastalerz-Migas, A and Kapusta, J}, title = {Persisting Smell and Taste Disorders in Patients Who Recovered from SARS-CoV-2 Virus Infection-Data from the Polish PoLoCOV-CVD Study.}, journal = {Viruses}, volume = {14}, number = {8}, pages = {}, pmid = {36016385}, issn = {1999-4915}, mesh = {Adult ; Aged ; Arthralgia ; *COVID-19/complications/epidemiology ; *Cardiovascular Diseases/complications ; Female ; Humans ; Male ; Middle Aged ; *Olfaction Disorders/diagnosis/epidemiology/etiology ; Poland/epidemiology ; SARS-CoV-2/pathogenicity ; Smell ; *Taste Disorders/diagnosis/epidemiology/etiology ; }, abstract = {In the majority of cases, patients infected with the SARS-CoV-2 virus experience a complete resolution of symptoms within six weeks of acquiring the infection, but an increasing number of patients report persistent symptoms. This study aimed to analyse the prevalence of self-reported smell and/or taste disorders (STDs) in a group of convalescent patients after infection with the SARS-CoV-2 virus and to identify risk factors for the disease. The study included 2218 COVID-19 convalescents after both inpatient and outpatient treatment. The sample group was analysed with regard to chronic diseases, place of isolation and clinical symptoms occurring during COVID-19 along with their duration. The assessment also included the most common symptoms of COVID-19 and the severity of the disease course. A total of 98 patients reported persistent smell and taste disorders up to three months after the end of isolation (67.4% of men and 32.6% of women). The mean age of the participants was 53.8 ± 13.5 years (49.19 ± 14.68 in patients with an STD vs. 54.01 ± 13.44 in patients without an STD). The patients treated for COVID-19 at home (p < 0.001) constituted almost the entire group of patients with persistent smell and taste disorders (97%). Among the patients with persistent smell and taste disorders, 57.1% suffered from at least one chronic condition (vs. 71.4% of patients without an STD). In patients with an STD, the number of symptoms per patient was higher than in the other group at 8.87 ± 3.65 (p = 0.018), while the most common clinical symptoms during the acute phase of COVID-19 were smell and taste disorders (84%) (p < 0.001), significant weakness (70%), headache (60%), cough (55%), arthralgia (51%) (p = 0.034) and back muscle pain (51%). Based on the results obtained, the following conclusions were drawn: the risk of developing persistent smell and taste disorders after COVID-19 is greater in younger people with less comorbidities and a higher number of symptoms during the acute phase of COVID-19. The risk is associated with clinical symptoms occurring during the acute phase of COVID-19, i.e., smell and taste disorders and arthralgia. In addition, this risk is higher in patients receiving outpatient treatment for COVID-19.}, } @article {pmid36016376, year = {2022}, author = {Chudzik, M and Babicki, M and Kapusta, J and Kałuzińska-Kołat, Ż and Kołat, D and Jankowski, P and Mastalerz-Migas, A}, title = {Long-COVID Clinical Features and Risk Factors: A Retrospective Analysis of Patients from the STOP-COVID Registry of the PoLoCOV Study.}, journal = {Viruses}, volume = {14}, number = {8}, pages = {}, pmid = {36016376}, issn = {1999-4915}, mesh = {*COVID-19/complications/epidemiology ; Cough/epidemiology/virology ; *Fatigue Syndrome, Chronic/epidemiology/virology ; Female ; Humans ; Mental Fatigue/epidemiology/virology ; Registries ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Despite recovering from the acute phase of coronavirus disease (COVID-19), many patients report continuing symptoms that most commonly include fatigue, cough, neurologic problems, hair loss, headache, and musculoskeletal pain, a condition termed long-COVID syndrome. Neither its etiopathogenesis, nor its clinical presentation or risk factors are fully understood. Therefore, the purpose of this study was to retrospectively evaluate the most common symptoms of long-COVID among patients from the STOP COVID registry of the PoLoCOV study, and to search for risk factors for development of the syndrome. The registry includes patients who presented to the medical center for persistent clinical symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The analysis included data from initial presentation and at three-month follow-up. Of the 2218 patients, 1569 (70.7%) reported having at least one symptom classified as long-COVID syndrome three months after recovery from the initial SARS-CoV-2 infection. The most common symptoms included chronic fatigue (35.6%\), cough (23.0%), and a set of neurological symptoms referred to as brain fog (12.1%). Risk factors for developing long-COVID syndrome included female gender (odds ratio [OR]: 1.48, 95% confidence intervals [CI] [1.19-1.84]), severe COVID-19 (OR: 1.56, CI: 1.00-2.42), dyspnea (OR: 1.31, CI: 1.02-1.69), and chest pain (OR: 1.48, CI: 1.14-1.92). Long-COVID syndrome represents a significant clinical and social problem. The most common clinical manifestations are chronic fatigue, cough, and brain fog. Given the still-limited knowledge of long-COVID syndrome, further research and observation are needed to better understand the mechanisms and risk factors of the disease.}, } @article {pmid36016309, year = {2022}, author = {Stafie, CS and Solomon, SM and Sufaru, IG and Manaila, M and Stafie, II and Melinte, G and Simionescu, B and Leustean, L}, title = {Pathogenic Connections in Post-COVID Conditions: What Do We Know in the Large Unknown? A Narrative Review.}, journal = {Viruses}, volume = {14}, number = {8}, pages = {}, pmid = {36016309}, issn = {1999-4915}, mesh = {Adult ; *COVID-19/complications/pathology ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.}, } @article {pmid36015250, year = {2022}, author = {Adami, R and Russo, P and Amante, C and De Soricellis, C and Della Porta, G and Reverchon, E and Del Gaudio, P}, title = {Supercritical Antisolvent Technique for the Production of Breathable Naringin Powder.}, journal = {Pharmaceutics}, volume = {14}, number = {8}, pages = {}, pmid = {36015250}, issn = {1999-4923}, abstract = {Flavonoids are polyphenolic compounds largely present in fruits and vegetables possessing antioxidant properties, anti-inflammatory and antibacterial activities. Their use in clinical practice is very poor due to their low bioavailability, susceptibility to oxidation and degradation. Moreover, their slight solubility in biological fluids and a consequent low dissolution rate leads to an irregular absorption from solid dosage forms, even though, anti-inflammatory formulations could be used as support for several disease treatment, i.e. the COVID-19 syndrome. To improve flavonoid bioavailability particle size of the powder can be reduced to make it breathable and to promote the absorption in the lung tissues. Supercritical fluid based antisolvent technique has been used to produce naringin particles, with size, shape and density as well as free flowing properties able to fit inhalation needs. The dried particles are produced with the removal of the solvent at lower temperatures compared to the most used traditional micronization processes, such as spray drying. The best breathable fraction for naringin particles is obtained for particles with a d50~7 µm manufactured at 35 °C-150 bar and at 60 °C-130 bar, corresponding to 32.6% and 36.7% respectively. The powder is produced using a high CO2 molar fraction (0.99) that assure a better removal of the solvent. NuLi-1 cell line of immortalised bronchial epithelial cells adopted to evaluate powder cytotoxicity indicated after 24 h absence of toxicity at concentration of 25 µM.}, } @article {pmid36015078, year = {2022}, author = {Nunes, JM and Kruger, A and Proal, A and Kell, DB and Pretorius, E}, title = {The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {8}, pages = {}, pmid = {36015078}, issn = {1424-8247}, support = {NNF10CC1016517//Novo Nordisk Foundation/ ; }, abstract = {We have previously demonstrated that platelet-poor plasma (PPP) obtained from patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state and contains hyperactivated platelets and considerable numbers of already-formed amyloid fibrin(ogen) or fibrinaloid microclots. Due to the substantial overlap in symptoms and etiology between Long COVID/PASC and ME/CFS, we investigated whether coagulopathies reflected in Long COVID/PASC-hypercoagulability, platelet hyperactivation, and fibrinaloid microclot formation-were present in individuals with ME/CFS and gender- and age-matched healthy controls. ME/CFS samples showed significant hypercoagulability as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated PPP from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed hyperactivation of platelets in ME/CFS hematocrit samples. Using a quantitative scoring system, the ME/CFS platelets were found to have a mean spreading score of 2.72 ± 1.24 vs. 1.00 (activation with pseudopodia formation) for healthy controls. We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, the fibrinaloid microclot load was not as great as was previously noted in Long COVID/PASC. Fibrinaloid microclots, in particular, may contribute to many ME/CFS symptoms, such as fatigue, seen in patients with ME/CFS, via the (temporary) blockage of microcapillaries and hence ischemia. Furthermore, fibrinaloid microclots might damage the endothelium. The discovery of these biomarkers represents an important development in ME/CFS research. It also points to possible uses for treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation.}, } @article {pmid36012469, year = {2022}, author = {Nishi, K and Yoshimoto, S and Nishi, S and Nishi, T and Nishi, R and Tanaka, T and Tsunoda, T and Imai, K and Tanaka, H and Hotta, O and Tanaka, A and Hiromatsu, K and Shirasawa, S and Nakagawa, T and Yamano, T}, title = {Epipharyngeal Abrasive Therapy (EAT) Reduces the mRNA Expression of Major Proinflammatory Cytokine IL-6 in Chronic Epipharyngitis.}, journal = {International journal of molecular sciences}, volume = {23}, number = {16}, pages = {}, pmid = {36012469}, issn = {1422-0067}, support = {0000//The Soda Toyoji Memorial Foundation/ ; }, mesh = {Cytokines/genetics ; Humans ; *Interleukin-6/genetics ; *Pharyngitis/therapy ; RNA, Messenger/genetics ; }, abstract = {The epipharynx, located behind the nasal cavity, is responsible for upper respiratory tract immunity; however, it is also the site of frequent acute and chronic inflammation. Previous reports have suggested that chronic epipharyngitis is involved not only in local symptoms such as cough and postnasal drip, but also in systemic inflammatory diseases such as IgA nephropathy and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID. Epipharyngeal Abrasive Therapy (EAT), which is an effective treatment for chronic epipharyngitis in Japan, is reported to be effective for these intractable diseases. The sedation of chronic epipharyngitis by EAT induces suppression of the inflammatory cytokines and improves systemic symptoms, which is considered to be one of the mechanisms, but there is no report that has proved this hypothesis. The purpose of this study was to clarify the anti-inflammatory effect of EAT histologically. The study subjects were 8 patients who were not treated with EAT and 11 patients who were treated with EAT for chronic epipharyngitis for 1 month or more. For immunohistochemical assessment, the expression pattern of IL-6 mRNA, which plays a central role in the human cytokine network, was analyzed using in situ hybridization. The expression of IL-6 in the EAT-treated group was significantly lower than those in the EAT nontreated group (p = 0.0015). In addition, EAT suppressed the expression of tumor necrosis factor alpha (TNFα), a crucial proinflammatory cytokine. As a result, continuous EAT suppressed submucosal cell aggregation and reduced inflammatory cytokines. Thus, EAT may contribute to the improvement of systemic inflammatory diseases through the suppression of IL-6 expression.}, } @article {pmid36011997, year = {2022}, author = {Maes, M and Al-Rubaye, HT and Almulla, AF and Al-Hadrawi, DS and Stoyanova, K and Kubera, M and Al-Hakeim, HK}, title = {Lowered Quality of Life in Long COVID Is Predicted by Affective Symptoms, Chronic Fatigue Syndrome, Inflammation and Neuroimmunotoxic Pathways.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011997}, issn = {1660-4601}, mesh = {Affective Symptoms ; Biomarkers ; *COVID-19/complications/epidemiology ; Calcium ; *Fatigue Syndrome, Chronic/epidemiology ; Female ; Humans ; Inflammation ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {The physio-affective phenome of Long COVID-19 is predicted by (a) immune-inflammatory biomarkers of the acute infectious phase, including peak body temperature (PBT) and oxygen saturation (SpO2), and (b) the subsequent activation of immune and oxidative stress pathways during Long COVID. The purpose of this study was to delineate the effects of PBT and SpO2 during acute infection, as well as the increased neurotoxicity on the physical, psychological, social and environmental domains of health-related quality of life (HR-QoL) in people with Long COVID. We recruited 86 participants with Long COVID and 39 normal controls, assessed the WHO-QoL-BREF (World Health Organization Quality of Life Instrument-Abridged Version, Geneva, Switzerland) and the physio-affective phenome of Long COVID (comprising depression, anxiety and fibromyalgia-fatigue rating scales) and measured PBT and SpO2 during acute infection, and neurotoxicity (NT, comprising serum interleukin (IL)-1β, IL-18 and caspase-1, advanced oxidation protein products and myeloperoxidase, calcium and insulin resistance) in Long COVID. We found that 70.3% of the variance in HR-QoL was explained by the regression on the physio-affective phenome, lowered calcium and increased NT, whilst 61.5% of the variance in the physio-affective phenome was explained by calcium, NT, increased PBT, lowered SpO2, female sex and vaccination with AstraZeneca and Pfizer. The effects of PBT and SpO2 on lowered HR-QoL were mediated by increased NT and lowered calcium yielding increased severity of the physio-affective phenome which largely affects HR-QoL. In conclusion, lowered HR-Qol in Long COVID is largely predicted by the severity of neuro-immune and neuro-oxidative pathways during acute and Long COVID.}, } @article {pmid36011562, year = {2022}, author = {Franco, JVA and Garegnani, LI and Oltra, GV and Metzendorf, MI and Trivisonno, LF and Sgarbossa, N and Ducks, D and Heldt, K and Mumm, R and Barnes, B and Scheidt-Nave, C}, title = {Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011562}, issn = {1660-4601}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Cross-Sectional Studies ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID-19 conditions, also known as 'Long-COVID-19', describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.}, } @article {pmid36011458, year = {2022}, author = {Wang, Y and Bao, S and Chen, Y}, title = {The Illness Experience of Long COVID Patients: A Qualitative Study Based on the Online Q&A Community Zhihu.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {16}, pages = {}, pmid = {36011458}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology ; Grounded Theory ; Humans ; Qualitative Research ; Social Stigma ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is a public health problem that cannot be ignored, and it is critical to understand the long COVID patients' living situations and support this group through their illness narratives. This study is based on grounded theory, and coded the self-produced texts of long COVID patients on the largest online Q&A community in China, Zhihu APP, in an attempt to explore the illness experiences of long COVID patients in China and to understand how they adapt to their illness and reconstruct their lives. The results show that patients face not only the threat of pain from the illness itself, but also social stigma and discrimination. Patients turn their illness experiences into motivation to move forward and reconstruct self and life by 'pushing forward the biographical flows again', 'impression management' and 'self-compassion'. These findings can help policy-makers and medical institutions to provide timely and appropriate policy support and psychological assistance to patients with long COVID, to create a supportive and inclusive social environment, and to reduce discrimination and stigma against them.}, } @article {pmid36010630, year = {2022}, author = {De Luca, P and Camaioni, A and Marra, P and Salzano, G and Carriere, G and Ricciardi, L and Pucci, R and Montemurro, N and Brenner, MJ and Di Stadio, A}, title = {Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010630}, issn = {2073-4409}, mesh = {Amides ; *COVID-19/complications ; Ethanolamines ; Female ; Humans ; Longitudinal Studies ; Luteolin/pharmacology/therapeutic use ; Male ; *Olfaction Disorders/drug therapy/epidemiology ; Palmitic Acids ; Smell ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence ("previously treated") or absence ("naïve") of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6-14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.}, } @article {pmid36010557, year = {2022}, author = {Zingaropoli, MA and Iannetta, M and Piermatteo, L and Pasculli, P and Latronico, T and Mazzuti, L and Campogiani, L and Duca, L and Ferraguti, G and De Michele, M and Galardo, G and Pugliese, F and Antonelli, G and Andreoni, M and Sarmati, L and Lichtner, M and Turriziani, O and Ceccherini-Silberstein, F and Liuzzi, GM and Mastroianni, CM and Ciardi, MR}, title = {Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010557}, issn = {2073-4409}, mesh = {Axons ; *Blood-Brain Barrier ; *COVID-19 ; Humans ; RNA, Viral ; SARS-CoV-2 ; }, abstract = {Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.}, } @article {pmid36010377, year = {2022}, author = {Lazar, M and Barbu, EC and Chitu, CE and Tiliscan, C and Stratan, L and Arama, SS and Arama, V and Ion, DA}, title = {Interstitial Lung Fibrosis Following COVID-19 Pneumonia.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010377}, issn = {2075-4418}, abstract = {Background and Objectives: Pulmonary fibrosis represents a stage of normal physiologic response to inflammatory aggression, mostly self-limiting and reversible; however, numerous patients treated for SARS-CoV-2 pneumonia present after release from hospital residual lung fibrosis. In this article, we aim to present an optimization method for evaluating pulmonary fibrosis by quantitative analysis, to identify the risk factors/predictors for pulmonary fibrosis in patients with SARS-CoV-2 infection, and to characterize the impact of pulmonary fibrosis on the symptomatology of patients after release from the hospital. Materials and Methods: We performed a prospective observational study on 100 patients with severe forms of pneumonia, with a control group of 61 non-COVID normal patients. Results: We found persistent interstitial changes consistent with fibrotic changes in 69% of patients. The risk of fibrosis was proportional to the values of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and lactate dehydrogenase (LDH), and to the duration of hospitalization. The imaging parameters correlated with increased risk for interstitial fibrosis were the number of affected pulmonary lobes and the percent of interstitial pulmonary fibrosis. Conclusions: The main risk factors for pulmonary fibrosis post-COVID-19 identified in our study are increased ESR, CRP, LDH, duration of hospitalization and the severity of pneumonia.}, } @article {pmid36010203, year = {2022}, author = {Khaswal, A and Kumar, V and Kumar, S}, title = {Long-Term Health Consequences of SARS-CoV-2: Assumptions Based on SARS-CoV-1 and MERS-CoV Infections.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010203}, issn = {2075-4418}, support = {K99AG065645/AG/NIA NIH HHS/United States ; }, abstract = {Coronavirus Disease-2019 (COVID-19) is one of the worst pandemics in the history of the world. It is the third coronavirus disease that has afflicted humans in a short span of time. The world appears to be recovering from the grasp of this deadly pandemic; still, its post-disease health effects are not clearly understood. It is evident that the vast majority of COVID-19 patients usually recovered over time; however, disease manifestation is reported to still exist in some patients even after complete recovery. The disease is known to have left irreversible damage(s) among some patients and these damages are expected to cause mild or severe degrees of health effects. Apart from the apparent damage to the lungs caused by SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection, COVID-19-surviving patients display a wide spectrum of dysfunctions in different organ systems that is similar to what occurs with SARS-CoV-1 and MERS diseases. The major long COVID-19 manifestations include the following aspects: (1) central nervous system, (2) cardiovascular, (3) pulmonary, (4) gastrointestinal, (5) hematologic, (6) renal and (7) psycho-social systems. COVID-19 has a disease display manifestation in these organs and its related systems amongst a large number of recovered cases. Our study highlights the expected bodily consequences of the pandemic caused by SARS-CoV-2 infection based on the understanding of the long-term effects of SARS-CoV-1 and MERS-CoV.}, } @article {pmid36010141, year = {2022}, author = {Buonsenso, D and Martino, L and Morello, R and De Rose, C and Valentini, P}, title = {Chronic Olfactory Dysfunction in Children with Long COVID: A Retrospective Study.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {8}, pages = {}, pmid = {36010141}, issn = {2227-9067}, support = {65925795//pfizer/ ; }, abstract = {Olfactory dysfunction is one of the long-term consequences of acute SARS-CoV-2 infection in adults. This study aims to analyze the prevalence of chronic anosmia among COVID-19 children and to bring to light its impact on their families' quality of life and wellbeing. Children younger than 18 years old, who were detected as being COVID-19-positive by RT-PCR and were assessed in a pediatric post-COVID outpatient clinic at least 28 days after the onset of the acute infection, were included in the study. The patients suffering from persisting smell disorders were asked to answer a questionnaire about their symptoms and how they influence their daily life. Out of the 784 children evaluated, 13 (1.7%) presented olfactory impairment at a mean follow-up since the acute infection of more than three months. Parents' answers showed that they were worried about their children's health, in particular they wanted to know if and when they would recover and if these disorders would have long-term consequences. They also wanted to share their experiences, in order to help other people who are experiencing the same disorders in everyday life. Our study highlights that smell disorders can significantly upset children's eating habits and everyday activities. Furthermore, these findings suggest that future research should try to better understand the mechanisms causing loss of smell in COVID-19 patients and find the most appropriate treatment.}, } @article {pmid36009498, year = {2022}, author = {Fernández-de-Las-Peñas, C and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Rodríguez-Jiménez, J and Gómez-Mayordomo, V and Torres-Macho, J and Pellicer-Valero, OJ and Martín-Guerrero, JD and Hernández-Barrera, V and Arendt-Nielsen, L}, title = {Prevalence of Musculoskeletal Post-COVID Pain in Hospitalized COVID-19 Survivors Depending on Infection with the Historical, Alpha or Delta SARS-CoV-2 Variant.}, journal = {Biomedicines}, volume = {10}, number = {8}, pages = {}, pmid = {36009498}, issn = {2227-9059}, support = {THE LONG-COVID-EXP-CM//Comunidad de Madrid/ ; 0067235//Novo Nordisk Foundation/ ; }, abstract = {We compared the prevalence of musculoskeletal post-COVID pain between previously hospitalized COVID-19 survivors infected with the historical, Alpha or Delta SARS-CoV-2 variant. Data about musculoskeletal post-COVID pain were systematically collected through a telephone interview involving 201 patients who had survived the historical variant, 211 who had survived the Alpha variant and 202 who had survived the Delta variant six months after hospital discharge. Participants were recruited from non-vaccinated individuals hospitalized due to SARS-CoV-2 infection in one hospital of Madrid (Spain) during three different waves of the pandemic (historical, Alpha or Delta variant). Hospitalization and clinical data were collected from hospital medical records. In addition, anxiety/depressive levels and sleep quality were also assessed. The prevalence of musculoskeletal post-COVID pain was higher (p = 0.003) in patients infected with the historical variant (47.7%) than in those infected with the Alpha (38.3%) or Delta (41%) variants. A significantly (p = 0.002) higher proportion of individuals infected with the historical variant reported generalized pain (20.5%) when compared with those infected with the other variants. The prevalence of new-onset post-COVID musculoskeletal pain reached 80.1%, 75.2% and 79.5% of patients infected with the historical, Alpha or Delta variants, respectively. No specific risk factors for developing post-COVID pain were identified depending on the SARS-CoV-2 variant. In conclusion, this study found that musculoskeletal post-COVID pain is highly prevalent in COVID-19 survivors six months after hospital discharge, with the highest prevalence and most generalized pain symptoms in individuals infected with the historical variant. Approximately 50% developed "de novo" post-COVID musculoskeletal pain symptoms.}, } @article {pmid36009268, year = {2022}, author = {Muchtaridi, M and Amirah, SR and Harmonis, JA and Ikram, EHK}, title = {Role of Nuclear Factor Erythroid 2 (Nrf2) in the Recovery of Long COVID-19 Using Natural Antioxidants: A Systematic Review.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009268}, issn = {2076-3921}, support = {2203/UN6.3.1/PT.00/2022//Padjadjaran University/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infectious disease with approximately 517 million confirmed cases, with the average number of cases revealing that patients recover immediately without hospitalization. However, several other cases found that patients still experience various symptoms after 3-12 weeks, which is known as a long COVID syndrome. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can activate nuclear factor kappa beta (NF-κβ) and unbind the nuclear factor erythroid 2-related factor 2 (Nrf2) with Kelch-like ECH-associated protein 1 (Keap1), causing inhibition of Nrf2, which has an important role in antioxidant response and redox homeostasis. Disrupting the Keap1-Nrf2 pathway enhances Nrf2 activity, and has been identified as a vital approach for the prevention of oxidative stress and inflammation. Hence, natural antioxidants from various sources have been identified as a promising strategy to prevent oxidative stress, which plays a role in reducing the long COVID-19 symptoms. Oxygen-rich natural antioxidant compounds provide an effective Nrf2 activation effect that interact with the conserved amino acid residues in the Keap1-binding pocket, such as Ser602, Ser363, Ser508, and Ser555. In this review, the benefits of various natural antioxidant compounds that can modulate the Nrf2 signaling pathway, which is critical in reducing and curing long COVID-19, are highlighted and discussed.}, } @article {pmid36009185, year = {2022}, author = {Crudele, A and Smeriglio, A and Ingegneri, M and Panera, N and Bianchi, M and Braghini, MR and Pastore, A and Tocco, V and Carsetti, R and Zaffina, S and Alisi, A and Trombetta, D}, title = {Hydroxytyrosol Recovers SARS-CoV-2-PLpro-Dependent Impairment of Interferon Related Genes in Polarized Human Airway, Intestinal and Liver Epithelial Cells.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {8}, pages = {}, pmid = {36009185}, issn = {2076-3921}, support = {POR FESR 14/20//Finpiemonte/ ; }, abstract = {The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects 10-20% of the individuals who have recovered from the infection. Scientific and clinical evidence demonstrates that long-COVID can develop in both adults and children. It has been hypothesized that multi-organ effects of long-COVID could be associated with the persistence of virus RNA/proteins in host cells, but the real mechanism remains to be elucidated. Therefore, we sought to determine the effects of the exogenous expression of the papain-like protease (PLpro) domain of the non-structural protein (NSP3) of SARS-CoV-2 in polarized human airway (Calu-3), intestinal (Caco-2), and liver (HepG2) epithelial cells, and to evaluate the ability of the natural antioxidant hydroxytyrosol (HXT) in neutralizing these effects. Our results demonstrated that PLpro was able to induce a cascade of inflammatory genes and proteins (mainly associated with the interferon pathway) and increase the apoptotic rate and expression of several oxidative stress markers in all evaluated epithelial cells. Noteably, the treatment with 10 μM HXT reverted PL-pro-dependent effects almost completely. This study provides the first evidence that SARS-CoV-2 PLpro remaining in host cells after viral clearance may contribute to the pathogenetic mechanisms of long-COVID. These effects may be counteracted by natural antioxidants. Further clinical and experimental studies are necessary to confirm this hypothesis.}, } @article {pmid36008721, year = {2022}, author = {Waltz, E}, title = {Could long COVID be linked to herpes viruses? Early data offer a hint.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {36008721}, issn = {1476-4687}, } @article {pmid36008115, year = {2022}, author = {Kachaner, A and Lemogne, C and Dave, J and Ranque, B and de Broucker, T and Meppiel, E}, title = {Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19).}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2021-327899}, pmid = {36008115}, issn = {1468-330X}, abstract = {OBJECTIVES: To assess the diagnosis of somatic symptom disorder (SSD) in patients with unexplained neurological symptoms occurring after SARS-CoV-2 infection, also referred to as long COVID.

DESIGN: Single-centre observational study.

PARTICIPANTS: Adult patients experiencing unexplained long-lasting neurological symptoms after mild COVID. Of the 58 consecutive patients referred in our centre, 50 were included.

INTERVENTION: Patients were contacted for a standardised psychometric evaluation by phone, followed by a self-survey.

MAIN OUTCOME: Positive diagnosis of SSD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).

RESULTS: Although the patients did not meet the DSM-5 criteria for a functional neurological symptom disorder specifically, SSD diagnosis based on DSM-5 criteria was positive in 32 (64%) patients. In the remaining 18 patients, SSD was considered possible given the high score on diagnostic scales. Physical examination were normal for all. Brain MRI showed unspecific minor white matter hyperintensities in 8/46 patients. Neuropsychological assessment showed exclusively mild impairment of attention in 14 out of 15 tested patients, in discrepancy with their major subjective complaint. Forty-five (90%) patients met criteria for Chronic Fatigue Syndrome. Seventeen (32%) patients were screened positive for mood-anxiety disorders, 19 (38%) had a history of prior SSD and 27 (54%) reported past trauma. Additional self-survey highlighted post-traumatic stress disorder in 12/43 (28%), high levels of alexithymia traits and perfectionism. Long-lasting symptoms had a major impact with a high rate of insomnia (29/43, 67%), psychiatric follow-up (28/50, 56%) and work or pay loss (25/50, 50%).

CONCLUSION: A majority of patients with unexplained long-lasting neurological symptoms after mild COVID met diagnostic criteria for SSD and may require specific management.

TRIAL REGISTRATION NUMBER: NCT04889313.}, } @article {pmid36007131, year = {2022}, author = {Koss, J and Bohnet-Joschko, S}, title = {Social Media Mining of Long-COVID Self-Medication Reported by Reddit Users: Feasibility Study to Support Drug Repurposing.}, journal = {JMIR formative research}, volume = {6}, number = {10}, pages = {e39582}, pmid = {36007131}, issn = {2561-326X}, abstract = {BACKGROUND: Since the beginning of the COVID-19 pandemic, over 480 million people have been infected and more than 6 million people have died from COVID-19 worldwide. In some patients with acute COVID-19, symptoms manifest over a longer period, which is also called "long-COVID." Unmet medical needs related to long-COVID are high, since there are no treatments approved. Patients experiment with various medications and supplements hoping to alleviate their suffering. They often share their experiences on social media.

OBJECTIVE: The aim of this study was to explore the feasibility of social media mining methods to extract important compounds from the perspective of patients. The goal is to provide an overview of different medication strategies and important agents mentioned in Reddit users' self-reports to support hypothesis generation for drug repurposing, by incorporating patients' experiences.

METHODS: We used named-entity recognition to extract substances representing medications or supplements used to treat long-COVID from almost 70,000 posts on the "/r/covidlonghaulers" subreddit. We analyzed substances by frequency, co-occurrences, and network analysis to identify important substances and substance clusters.

RESULTS: The named-entity recognition algorithm achieved an F1 score of 0.67. A total of 28,447 substance entities and 5789 word co-occurrence pairs were extracted. "Histamine antagonists," "famotidine," "magnesium," "vitamins," and "steroids" were the most frequently mentioned substances. Network analysis revealed three clusters of substances, indicating certain medication patterns.

CONCLUSIONS: This feasibility study indicates that network analysis can be used to characterize the medication strategies discussed in social media. Comparison with existing literature shows that this approach identifies substances that are promising candidates for drug repurposing, such as antihistamines, steroids, or antidepressants. In the context of a pandemic, the proposed method could be used to support drug repurposing hypothesis development by prioritizing substances that are important to users.}, } @article {pmid36004306, year = {2022}, author = {Choudhury, A and Tariq, R and Jena, A and Vesely, EK and Singh, S and Khanna, S and Sharma, V}, title = {Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221118403}, pmid = {36004306}, issn = {1756-283X}, abstract = {BACKGROUND: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic.

OBJECTIVES: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID.

DESIGN: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed.

DATA SOURCES AND METHODS: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages 'meta' and 'metafor'.

RESULTS: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06-0.22, I [2] = 99%] and 0.22 (95% CI, 0.10-0.41, I [2] = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04-0.38, I [2] = 96%), 0.06 (95% CI, 0.03-0.11, I [2] = 98%), 0.20 (95% CI, 0.08-0.43, I [2] = 98%), and 0.17 (95% CI, 0.10-0.27, I [2] = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04-0.23, I [2] = 98%), 0.20 (95% CI, 0.06-0.50, I [2] = 97%), and 0.17 (95% CI, 0.06-0.37, I [2] = 96%), respectively.

CONCLUSION: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.}, } @article {pmid36004011, year = {2022}, author = {Boehm, BA and Packer, CD}, title = {Persistent Relapsing Immune Thrombocytopenia Following COVID-19 Infection.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e27133}, pmid = {36004011}, issn = {2168-8184}, abstract = {Immune thrombocytopenia (ITP) is a rare autoimmune disease that presents along a spectrum of disease severity, ranging from asymptomatic thrombocytopenia to potentially life-threatening bleeding complications. Recent case reports and case series suggest that a COVID-19 infection can trigger secondary ITP and may be associated with higher rates of bleeding and lower nadir platelet counts compared to patients with ITP of other etiologies. Multiple ITP relapses have also been described in some COVID-19 patients. We report the case of a 30-year-old otherwise healthy woman who presented to the hospital with fatigue, easy bruising, and a platelet count of 11 x 10[3]/µL. She responded well to our initial treatment with prednisone and intravenous immunoglobulin (IVIG) but experienced a persistent disease course with nine ITP relapses (defined as platelet count <30 x 10[3]/µL) over the next 10.5 months, requiring six additional hospital admissions for acute management as well as long-term maintenance medication adjustments. It is important for clinicians to recognize ITP as a potential complication of a COVID-19 infection and to initiate early therapy to prevent serious bleeding in these patients. Further studies will be needed to understand the natural history, optimal treatment, and prognosis for patients with relapsing COVID-19-associated ITP.}, } @article {pmid36003084, year = {2022}, author = {Chan Sui Ko, A and Candellier, A and Mercier, M and Joseph, C and Carette, H and Basille, D and Lion-Daolio, S and Devaux, S and Schmit, JL and Lanoix, JP and Andrejak, C}, title = {No Impact of Corticosteroid Use During the Acute Phase on Persistent Symptoms Post-COVID-19.}, journal = {International journal of general medicine}, volume = {15}, number = {}, pages = {6645-6651}, pmid = {36003084}, issn = {1178-7074}, abstract = {Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58-1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients.}, } @article {pmid36002874, year = {2022}, author = {Badran, BW and Huffman, SM and Dancy, M and Austelle, CW and Bikson, M and Kautz, SA and George, MS}, title = {A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms.}, journal = {Bioelectronic medicine}, volume = {8}, number = {1}, pages = {13}, pmid = {36002874}, issn = {2332-8886}, support = {P20 GM109040/GM/NIGMS NIH HHS/United States ; P2C HD086844/HD/NICHD NIH HHS/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; U54GM104941-08//Delaware Clinical and Translational Research ACCEL Program/ ; }, abstract = {BACKGROUND: Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively.

METHODS: We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered on ClinicalTrials.gov under the identifier: NCT04638673 registered November 20, 2020.

RESULTS: Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals.

CONCLUSIONS: This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.}, } @article {pmid36002482, year = {2022}, author = {Willyard, C}, title = {Could tiny blood clots cause long COVID's puzzling symptoms?.}, journal = {Nature}, volume = {608}, number = {7924}, pages = {662-664}, pmid = {36002482}, issn = {1476-4687}, mesh = {*COVID-19/complications/pathology/virology ; Humans ; *SARS-CoV-2/pathogenicity ; *Thrombosis/complications/pathology/virology ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid36002109, year = {2023}, author = {Mammi, P and Ranza, E and Rampello, A and Ravanetti, D and Cavaldonati, A and Moretti, S and Gobbi, E and Rodà, F and Brianti, R}, title = {Post-COVID-19 Ongoing Symptoms and Health-Related Quality of Life: Does Rehabilitation Matter?: Preliminary Evidence.}, journal = {American journal of physical medicine & rehabilitation}, volume = {102}, number = {3}, pages = {241-244}, pmid = {36002109}, issn = {1537-7385}, mesh = {Humans ; *Quality of Life ; *COVID-19 ; Pain ; Dyspnea/etiology ; Fatigue/etiology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Individuals with persisting symptoms after coronavirus disease 2019 have reported a decrease in health-related quality of life. This study explores the outcome of 50 subjects with post-coronavirus disease 2019 ongoing symptoms including "long COVID"(symptoms lasting over 3 mos), after a rehabilitation program focused on three symptoms: fatigue, breathlessness, and pain. The aims were as follows: to assess the feasibility of the program, to observe a possible change in symptoms and quality of life (null hypothesis: no differences in variables before and after treatment), and to investigate a possible relationship between symptoms and quality of life.

DESIGN: This is a retrospective observational study.

RESULTS: Symptoms intensity measured with numeric rating scale decreased. Mean differences are as follows: breathlessness, -2.91; fatigue, -2.05; and pain, -2.41 (P > 0.001). Quality of life measured with Euroqol-5D improved. Mean differences are as follows: Euroqol-5D index, 0.104, and Euroqol-5D visual analog scale, 19.21 (P < 0.001). Effect size of these changings is classifiable as large (Cohen d > 0.8 and <1.3) except for Euroqol-5D index (Cohen d = -0.575), resulting medium (>0.5 and <0.8). Correlation (Pearson r) between symptoms and Euroqol-5D resulted moderate for pain and fatigue (-0.609 and -0.531, P < 0.001) and low for breathlessness (-0.533, P < 0.001).

CONCLUSIONS: Rehabilitation can be feasible and may improve symptoms and quality of life. Further research is needed.}, } @article {pmid35999838, year = {2022}, author = {Taquet, M and Harrison, PJ}, title = {Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study.}, journal = {Brain communications}, volume = {4}, number = {4}, pages = {fcac206}, pmid = {35999838}, issn = {2632-1297}, abstract = {Post-COVID cognitive deficits (often referred to as 'brain fog') are common and have large impacts on patients' level of functioning. No specific intervention exists to mitigate this burden. This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with epilepsy taking phenytoin (a commonly used receptor-interacting protein kinase inhibitor) versus valproate or levetiracetam at the time of COVID-19 diagnosis. Patients taking phenytoin at the time of COVID-19 were at a significantly lower risk of cognitive deficits in the 6 months after COVID-19 infection than a matched cohort of patients receiving levetiracetam (hazard ratio 0.78, 95% confidence interval 0.63-0.97, P = 0.024) or valproate (hazard ratio 0.73, 95% confidence interval 0.58-0.93, P = 0.011). In secondary analyses, results were robust when controlling for subtype of epilepsy, and showed specificity to cognitive deficits in that similar associations were not seen with other 'long-COVID' outcomes such as persistent breathlessness or pain. These findings provide pharmacoepidemiological support for the hypothesis that receptor-interacting protein kinase signaling is involved in post-COVID cognitive deficits. These results should prompt empirical investigations of receptor-interacting protein kinase inhibitors in the prevention of post-COVID cognitive deficits.}, } @article {pmid35999605, year = {2022}, author = {Wolf, S and Zechmeister-Koss, I and Erdös, J}, title = {Possible long COVID healthcare pathways: a scoping review.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {1076}, pmid = {35999605}, issn = {1472-6963}, mesh = {*COVID-19/complications/epidemiology ; *Coronavirus ; *Coronavirus Infections/epidemiology/therapy ; Delivery of Health Care ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Individuals of all ages and with all degrees of severity of the coronavirus disease (COVID) can suffer from persisting or reappearing symptoms called long COVID. Long COVID involves various symptoms, such as shortness of breath, fatigue, or organ damage. The growing number of long COVID cases places a burden on the patients and the broader economy and, hence, has gained more weight in political decisions. This scoping review aimed to give an overview of recommendations about possible long COVID healthcare pathways and requirements regarding decision-making and communication for healthcare professionals.

METHODS: A systematic search in four databases and biweekly update-hand searches were conducted. In addition to guidelines and reviews, expert opinions in consensus statements or clinical perspectives were also considered. Data were systematically extracted and subsequently narratively and graphically summarised.

RESULTS: Fourteen references, five guidelines, four reviews, one consensus paper, and four clinical perspectives were included. The evidence recommended that most long COVID-related healthcare should be in primary care. Patients with complex symptoms should be referred to specialized long COVID outpatient assessment clinics. In contrast, patients with one dominant symptom should be directed to the respective specialist for a second assessment. Depending on the patients' needs, further referral options include, e.g. rehabilitation or non-medical health services. Self-management and good communication between healthcare professionals and patients are crucial aspects of the long COVID management recommendations.

CONCLUSIONS: The quality of the included guidelines and reviews is limited in the methods applied due to the novelty of this topic and the associated urgency for research. Hence, an update review with more rigorous data is recommended. Furthermore, the systematic collection of real-world data on long COVID surveillance needs to be set up soon to gather further information on the duration and severity of long COVID and thereby facilitate long COVID care planning.}, } @article {pmid35999107, year = {2022}, author = {Kanaan, CN and Iskandar, JP and Gad, MM and Kondoleon, NP and Mirzai, S and Hsich, EM and Estep, JD and Fares, MA}, title = {Outcomes Associated With COVID-19 Hospitalization in Heart Transplantation Patients.}, journal = {Transplantation proceedings}, volume = {54}, number = {10}, pages = {2688-2691}, pmid = {35999107}, issn = {1873-2623}, support = {R01 HL141892/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; Hospitalization ; *Heart Transplantation/adverse effects ; }, abstract = {BACKGROUND: Heart transplantation (HT) recipients infected with COVID-19 may be at an increased risk of severe illness due to chronic immunosuppression.

MATERIALS AND METHODS: Adult HT patients hospitalized with COVID-19 at the Cleveland Clinic between March 2020 and March 2021 were included in this retrospective cohort analysis. Twenty-four HT cases were matched to 96 non-HT controls, similarly hospitalized with COVID-19, out of 11,481 patients based on different baseline characteristics. Primary outcome was all-cause mortality; secondary outcomes included mechanical ventilation, intensive care unit admission, vasopressor need, dialysis, pneumonia, and 90-day readmission. Subgroup analysis was performed based on the time from transplantation (within 1 year of transplantation and greater than 1 year since transplantation).

RESULTS: Both primary and secondary outcomes were not significant. Subgroup analysis did not show a significant difference in mortality (P = .355) or 30-day readmission (P = .841) between patients who were within 1 year of transplantation and remote transplantation beyond 1 year. Univariable analysis of immunosuppressant continuation, dose-reduction, or discontinuation did not significantly affect HT mortality.

CONCLUSIONS: Despite limited sample size, our results suggest that HT patients do not show worse outcomes after acquiring COVID-19, whether in the first year of transplantation or after a remote transplantation procedure. Future studies with multicenter data that incorporate the subsequent COVID-19 variants (eg, Delta and Omicron), the impact of long COVID-19, and assessing full vs reduced immunosuppression regimens would add insights to this patient population.}, } @article {pmid35998959, year = {2022}, author = {Williamson, AE and Tydeman, F and Miners, A and Pyper, K and Martineau, AR}, title = {Short-term and long-term impacts of COVID-19 on economic vulnerability: a population-based longitudinal study (COVIDENCE UK).}, journal = {BMJ open}, volume = {12}, number = {8}, pages = {e065083}, pmid = {35998959}, issn = {2044-6055}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Longitudinal Studies ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To determine whether COVID-19 has a significant impact on adequacy of household income to meet basic needs (primary outcome) and work absence due to sickness (secondary outcome), both at the onset of illness (short term) and subsequently (long term).

DESIGN: Multilevel mixed regression analysis of self-reported data from monthly online questionnaires, completed 1 May 2020 to 28 October 2021, adjusting for baseline characteristics including age, sex, socioeconomic status and self-rated health.

SETTING AND PARTICIPANTS: Participants (n=16 910) were UK residents aged 16 years or over participating in a national longitudinal study of COVID-19 (COVIDENCE UK).

RESULTS: Incident COVID-19 was independently associated with increased odds of participants reporting household income as being inadequate to meet their basic needs in the short term (adjusted OR (aOR) 1.39, 95% CI 1.12 to 1.73) though this did not persist in the long term (aOR 1.00, 95% CI 0.86 to 1.16). Exploratory analysis revealed a stronger short-term association among those who reported long COVID, defined as the presence of symptoms lasting more than 4 weeks after disease onset, than those reporting COVID-19 without long COVID (p for trend 0.002). Incident COVID-19 associated with increased odds of reporting sickness absence from work in the long term (aOR 4.73, 95% CI 2.47 to 9.06) but not in the short term (aOR 1.34, 95% CI 0.52 to 3.49).

CONCLUSIONS: We demonstrate an independent association between COVID-19 and increased risk of economic vulnerability among COVIDENCE participants, measured by both household income sufficiency and sickness absence from work. Taking these findings together with pre-existing research showing that socioeconomic disadvantage increases the risk of developing COVID-19, this may suggest a 'vicious cycle' of impaired health and poor economic outcomes.

TRIAL REGISTRATION NUMBER: NCT04330599.}, } @article {pmid35996191, year = {2022}, author = {Zhong, LL and Wong, YP and Leung, CY and Peng, B and Lin, ZX and Wong Taam, VC and Luo, Y and Chen, HY and Chao, CD and Wong, CF and Tam, FS and Chan, K and Lee, KY and Ho, LF and Wong, AY and Choy, CF and Ng, BF and Wong, RH and Feng, YB and Liong, C and Bian, ZX and , }, title = {Effects of Chinese medicine for COVID-19 rehabilitation: a multicenter observational study.}, journal = {Chinese medicine}, volume = {17}, number = {1}, pages = {99}, pmid = {35996191}, issn = {1749-8546}, support = {HA 105/48 PT35//Hospital Authority/ ; }, abstract = {OBJECTIVES: This study aimed to evaluate the effects of Chinese Medicine (CM) on the health condition of the post-COVID-19 patients, particularly with the CM Syndrome diagnosis and Body Constitutions (BC), as well as related clinical characteristics.

METHODS: 150 participants who had COVID-19 and discharged from Hong Kong public hospitals were recruited. They were provided with three to six months of CM treatments, during which assessments were made per month and at follow-up on their CM syndromes, BC, lung functions, and other medical conditions. This study was divided into two parts: (1) Retrospective survey: medical history of participants during COVID-19 hospitalization was collected during the baseline visit; (2) Prospective observation and assessments: clinical symptoms, lung functions, and BC status were evaluated in participants receiving CM treatment based on syndrome differentiation and clinical symptoms.

RESULTS: The median hospitalization period was 16 days. Symptoms were presented in 145 (96.6%) patients at the day they were diagnosed with COVID-19. Fever, fatigue, and dry cough were the most common symptoms, exhibiting in 59.3% (89 of 150), 55.3% (83 of 150), and 46% (70 of 150) participants, respectively. Among the 150 post-COVID patients, majority (71.3%) were of the two particular post-COVID CM Syndromes (Qi Deficiency of Lung and Spleen, and Qi and Yin Deficiency). Upon CM treatment, there was an observable increase in participants reaching a balanced BC (i.e. healthy body conditions). The increase was observed to be more prominent in those without the particular CM Syndromes compared to those with the CM Syndromes. Main clinical symptoms in participants with the CM Syndromes decreased upon CM treatment. Occurrence of fatigue also dropped after CM treatment though not all accompanied clinical symptoms were resolved fully. Further to the improvement in terms of CM assessments, lung functions of the participants were found to show improvement after treatment. Both the performance in 6MWT and scores in the LFQ improved upon CM treatments (P < 0.05).

CONCLUSION: This study provided evidence for individualized CM treatment on COVID-19 rehabilitation concerning the clinical symptoms improvements, lung functions improvement, and achieving a balanced BC. It is believed that CM may be a key to further promote rehabilitation and resolution of residual symptoms. Long-term large scale follow-up studies on sub-categorising post-COVID patients according to different CM syndromes would be required to further elucidate treatment of persistent symptoms that may be associated with long-COVID.}, } @article {pmid35995059, year = {2022}, author = {Platz, T and Dewey, S and Köllner, V and Schlitt, A}, title = {[Rehabilitation with coronavirus disease with SARS-CoV-2 (COVID-19)].}, journal = {Die Rehabilitation}, volume = {61}, number = {4}, pages = {297-310}, doi = {10.1055/a-1746-4828}, pmid = {35995059}, issn = {1439-1309}, mesh = {*COVID-19/complications ; Germany ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The Coronavirus disease with SARS-CoV-2 viral infection (COVID-19) and its diverse courses of disease from mild to critical illness frequently is not only an acute disease, but will - in a proportion of those affected - lead to organ structure and body function deficits that still exist or become apparent after the acute stage of disease. When clinically relevant symptoms or functional deficits (impairments) are documented more than four weeks after COVID-19 onset, the syndrome is called "Long-COVID", from 12 weeks after onset onwards "Post-COVID".In such cases and when everyday life functioning and return to work are affected by persisting deficits specialized rehabilitation treatment is indicated. An individual medical, frequently multi-professional diagnostic evaluation is mandatory in that situation: For adequate treatment, it is important to identify and objectify the individually underlying health conditions based on knowledge about the diverse potential consequences of COVID-19, to assess type and severity of functional consequences (impairments, activity limitations, and restrictions of participation) of Long-/Post-COVID individually, and then to decide on the treatment necessities and plans. With regard to rehabilitation, need and decision for either pulmonary, neurological, cardiac, or psychosomatic rehabilitation depends on the individual medical presentation.}, } @article {pmid35994869, year = {2022}, author = {Michelutti, M and Furlanis, G and Buoite Stella, A and Bellavita, G and Frezza, N and Torresin, G and Ajčević, M and Manganotti, P}, title = {Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service.}, journal = {Journal of the neurological sciences}, volume = {441}, number = {}, pages = {120355}, pmid = {35994869}, issn = {1878-5883}, mesh = {*COVID-19/complications/epidemiology ; Female ; Humans ; Male ; *Neurology ; Retrospective Studies ; SARS-CoV-2 ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {"Long-COVID" is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection. We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups. Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049). Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.}, } @article {pmid35994135, year = {2022}, author = {Ser, MH and Çalıkuşu, FZ and Tanrıverdi, U and Abbaszade, H and Hakyemez, S and Balkan, İİ and Karaali, R and Gündüz, A}, title = {Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {11}, pages = {6167-6177}, pmid = {35994135}, issn = {1590-3478}, mesh = {Humans ; *COVID-19 ; Autonomic Nervous System ; Galvanic Skin Response ; *Diabetic Neuropathies/diagnosis ; Skin/innervation ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology.

METHODS: Step 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis.

RESULTS: There were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate.

CONCLUSION: Neuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.}, } @article {pmid35993433, year = {2022}, author = {Singh, J and Bhagaloo, L and Sy, E and Lavoie, AJ and Dehghani, P and Bardutz, HA and Mang, CS and Buttigieg, J and Neary, JP}, title = {Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept.}, journal = {Physiological reports}, volume = {10}, number = {16}, pages = {e15430}, pmid = {35993433}, issn = {2051-817X}, mesh = {*COVID-19/complications ; Echocardiography ; Humans ; Systole ; *Ventricular Dysfunction, Right ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although acute COVID-19 is known to cause cardiac damage in some cases, there is still much to learn about the duration and relative permanence of the damage that may occur. Long COVID is a condition that can occur when COVID-19 symptoms remain in the postviral acute period. Varying accounts of long COVID have been described across the literature, however, cardiac impairments are sustained in many individuals and cardiovascular assessment is now considered to be an expected follow-up examination. The purpose of this review and proof of concept is to summarize the current research related to the assessment of cardiac function, including echocardiography and blood biomarker data, during the follow-up period in patients who recovered from COVID-19. Following a literature review, it was found that right ventricular dysfunction along with global longitudinal strain and diastolic dysfunction are common findings. Finally, more severe acute myocardial injury during the index hospitalization appears to exacerbate cardiac function. The available literature implies that cardiac function must be monitored in patients recovered from COVID-19 who remain symptomatic and that the impairments and severity vary from person-to-person. The proof-of-concept analysis of patients with cardiac disease and respiratory disease in comparison to those with sustained symptoms from COVID-19 suggests elevated systolic time interval in those with sustained symptoms from COVID-19, thus reducing heart performance indices. Future research must consider the details of cardiac complications during the acute infection period and relate this to the cardiac function in patients with long COVID during mid- and long-term follow-up.}, } @article {pmid35992025, year = {2022}, author = {Field, RE}, title = {Long Covid - a cause of concern for surgical training.}, journal = {Journal of hip preservation surgery}, volume = {9}, number = {3}, pages = {143-144}, pmid = {35992025}, issn = {2054-8397}, } @article {pmid35990753, year = {2022}, author = {Murugesu, JA}, title = {Long covid struck 1 in 8 adults who got infected.}, journal = {New scientist (1971)}, volume = {255}, number = {3399}, pages = {9}, doi = {10.1016/S0262-4079(22)01416-6}, pmid = {35990753}, issn = {0262-4079}, } @article {pmid35989844, year = {2022}, author = {Okayasu, T and Ohta, R and Igarashi, M and Kurita, Y and Hayakawa, M and Sano, C}, title = {Coexistence of Pancytopenia and Myositis After Developing COVID-19.}, journal = {Cureus}, volume = {14}, number = {7}, pages = {e26978}, pmid = {35989844}, issn = {2168-8184}, abstract = {COVID-19 causes not only acute but also subacute medical conditions during the clinical course. COVID-19 causes severe inflammatory conditions; therefore, patients may develop long-term complications. Among patients with acute COVID-19, some patients can experience persistent symptoms, such as fatigue, joint pain, and smell and taste abnormalities, known as the long COVID-19 syndrome. The symptoms can be severe and require continuous medical care. Patients with severe clinical courses of COVID-19 may have critical symptoms again after the cure of the acute infections, especially among older patients. We encountered a case of neutropenia and myositis one month after contracting COVID-19. An 89-year-old man presented to our hospital with acute-onset systemic muscle pain and difficulty in movement and speaking. The patient had neutropenia and myositis with an extremely high level of immunoglobulin G caused by COVID-19. A granulocyte colony-stimulating factor could be effective for treating neutropenia. Besides, prednisolone was effective for treating myositis. In community hospitals, after developing COVID-19, appropriate history taking and physical examination should be performed in older patients with ambiguous symptoms, as they might have critical medical conditions such as neutropenia and myositis. The appropriate diagnosis and treatments of older patients with the complications of COVID-19 should be performed.}, } @article {pmid35988361, year = {2022}, author = {Degen, CV and Mikuteit, M and Niewolik, J and Joosten, T and Schröder, D and Vahldiek, K and Mücke, U and Heinemann, S and Müller, F and Behrens, GMN and Klawonn, F and Lenarz, T and Dopfer-Jablonka, A and Steffens, S}, title = {Audiological profile of adult Long COVID patients.}, journal = {American journal of otolaryngology}, volume = {43}, number = {5}, pages = {103579}, pmid = {35988361}, issn = {1532-818X}, mesh = {Adult ; Audiometry, Pure-Tone ; Auditory Threshold ; *COVID-19/complications ; *Hearing Loss, Sensorineural/diagnosis ; Humans ; Otoacoustic Emissions, Spontaneous ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Hearing loss is one of the self-reported symptoms of Long COVID patients, however data from objective and subjective audiological tests demonstrating diminished hearing in Long COVID patients has not been published.

MATERIALS AND METHODS: Respondents of a large Long COVID online survey were invited to the ENT-department for an otologic exam. The participants were split into three groups based on their history of SARS-CoV-2 infection and persistence of symptoms. Respondents with a history of a SARS-CoV-2 infection were allocated to the Long COVID group, if they reported persistent symptoms and to the Ex COVID group, if they had regained their previous level of health. Participants without a history of SARS-CoV-2 infection made up the No COVID control group. In total, 295 ears were examined with otoscopy, tympanograms, pure tone audiometry and otoacoustic emissions. Ears with known preexisting hearing loss or status post ear surgery, as well as those with abnormal otoscopic findings, non-type A tympanograms or negative Rinne test were excluded.

RESULTS: Compared to the No COVID and Ex COVID groups, we did not find a clinically significant difference in either hearing thresholds or frequency specific TEOAEs. However, at 500 Hz the data from the left ear, but not the right ear showed a significantly better threshold in the Ex COVID group, compared to Long COVID and No COVID groups. Any of the other tested frequencies between 500 Hz and 8 kHz were not significantly different between the different groups. There was a significantly lower frequency-specific signal-to-noise-ratio of the TEOAEs in the Long COVID compared to the No COVID group at 2.8 kHz. At all other frequencies, there were no significant differences between the three groups in the TEOAE signal-to-noise-ratio.

CONCLUSION: This study detected no evidence of persistent cochlear damage months after SARS-CoV-2 infection in a large cohort of Long COVID patients, as well as those fully recovered.}, } @article {pmid35986269, year = {2022}, author = {Tsuzuki, S and Miyazato, Y and Terada, M and Morioka, S and Ohmagari, N and Beutels, P}, title = {Impact of long-COVID on health-related quality of life in Japanese COVID-19 patients.}, journal = {Health and quality of life outcomes}, volume = {20}, number = {1}, pages = {125}, pmid = {35986269}, issn = {1477-7525}, support = {18K17369//Japan Society for the Promotion of Science/ ; 20K10546//Japan Society for the Promotion of Science/ ; 20A05//National Center for Global Health and Medicine/ ; JP20fk0108502//Japan Agency for Medical Research and Development/ ; Research for risk assessment//Ministry of Health, Labour and Welfare/ ; implementation of crisis management functions for emerging//Ministry of Health, Labour and Welfare/ ; re-emerging infectious diseases//Ministry of Health, Labour and Welfare/ ; }, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Health Status ; Humans ; Japan/epidemiology ; *Quality of Life ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The empirical basis for a quantitative assessment of the disease burden imposed by long-COVID is currently scant. We aimed to inform the disease burden caused by long-COVID in Japan.

METHODS: We conducted a cross sectional self-report questionnaire survey. The questionnaire was mailed to 526 eligible patients, who were recovered from acute COVID-19 in April 2021. Answers were classified into two groups; participants who have no symptom and those who have any ongoing prolonged symptoms that lasted longer than four weeks at the time of the survey. We estimated the average treatment effect (ATE) of ongoing prolonged symptoms on EQ-VAS and EQ-5D-3L questionnaire using inverse probability weighting. In addition to symptom prolongation, we investigated whether other factors (including demography, lifestyle, and acute severity) were associated with low EQ-VAS and EQ-5D-3L values, by multivariable linear regression.

RESULTS: 349 participants reported no symptoms and 108 reported any symptoms at the time of the survey. The participants who reported any symptoms showed a lower average value on the EQ-VAS (69.9 vs 82.8, respectively) and on the EQ-5D-3L (0.85 vs 0.96, respectively) than those reporting no symptoms considering the ATE of ongoing prolonged symptoms. The ATE of ongoing prolonged symptoms on EQ-VAS was - 12.9 [95% CI - 15.9 to - 9.8], and on the EQ-5D-3L it was - 0.11 [95% CI - 0.13 to - 0.09], implying prolonged symptoms have a negative impact on patients' EQ-VAS and EQ-5D-3L score. In multivariable linear regression, only having prolonged symptoms was associated with lower scores (- 11.7 [95% CI - 15.0 to - 8.5] for EQ-VAS and - 0.10 [95% CI - 0.13 to - 0.08] for EQ-5D-3L).

CONCLUSIONS: Due to their long duration, long-COVID symptoms represent a substantial disease burden expressed in impact on health-related quality of life.}, } @article {pmid35984816, year = {2023}, author = {Wiemken, TL and McGrath, LJ and Andersen, KM and Khan, F and Malhotra, D and Alfred, T and Nguyen, JL and Puzniak, L and Thoburn, E and Jodar, L and McLaughlin, JM}, title = {Coronavirus Disease 2019 Severity and Risk of Subsequent Cardiovascular Events.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {3}, pages = {e42-e50}, pmid = {35984816}, issn = {1537-6591}, mesh = {Adult ; Humans ; United States/epidemiology ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Retrospective Studies ; COVID-19 Testing ; Intensive Care Units ; Hospitalization ; *Heart Diseases ; }, abstract = {BACKGROUND: Little is known about the relationship between coronavirus disease 2019 (COVID-19) severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of United States adults.

METHODS: Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between 1 April 2020 and 31 May 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 days after COVID-19 diagnosis using inverse probability of treatment-weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only.

RESULTS: A total of 1 357 518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [aHR], 1.80 [95% confidence interval {CI}, 1.71-1.89]) or non-ICU hospitalization (aHR, 1.28 [95% CI, 1.24-1.33]). Risk of subsequent hospitalization for CVE was even higher (aHRs, 3.47 [95% CI, 3.20-3.76] for ICU and 1.96 [95% CI, 1.85-2.09] for non-ICU hospitalized vs outpatient only).

CONCLUSIONS: COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder COVID-19 who were managed solely in the outpatient setting, even after adjusting for differences between these groups. These findings underscore the continued importance of preventing severe acute respiratory syndrome coronavirus 2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.}, } @article {pmid35984763, year = {2022}, author = {Longobardi, I and Prado, DMLD and Goessler, KF and Meletti, MM and de Oliveira Júnior, GN and de Andrade, DCO and Gualano, B and Roschel, H}, title = {Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {323}, number = {3}, pages = {H569-H576}, pmid = {35984763}, issn = {1522-1539}, mesh = {*COVID-19 ; Cross-Sectional Studies ; Exercise ; Exercise Test/methods ; Exercise Tolerance/physiology ; Humans ; Kinetics ; Oxygen/metabolism ; *Oxygen Consumption/physiology ; SARS-CoV-2 ; Survivors ; }, abstract = {The post-acute phase of coronavirus disease 2019 (COVID-19) is often marked by several persistent symptoms and exertional intolerance, which compromise survivors' exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (V̇o2) kinetics and cardiopulmonary function in survivors of severe COVID-19 about 3-6 mo after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5 ± 1 mo after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximum-graded cardiopulmonary exercise test (CPX) with an initial 3-min period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). V̇o2 kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% (P = 0.008) and 28% (P = 0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed an 11% longer (P = 0.046) half-time of recovery of V̇o2 (T1/2V̇o2) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. Peak oxygen uptake (V̇o2peak), percent-predicted V̇o2peak, and V̇o2 at the ventilatory threshold (V̇o2VT) were reduced by 17%, 17%, and 12% in COVID-19 survivors, respectively (all P < 0.05). None of the ventilatory parameters differed between groups (all P > 0.05). In addition, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P < 0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which V̇o2 is adjusted to changes in energy demands.NEW & NOTEWORTHY Our findings provide novel data regarding the impact of COVID-19 on submaximal and maximal cardiopulmonary responses to exercise. We showed that V̇o2 kinetics is significantly impaired at both the onset (on-transient) and the recovery phase (off-transient) of exercise in these patients. Furthermore, our results suggest that survivors of severe COVID-19 may have a higher metabolic demand at a walking pace. These findings may partly explain the exertional intolerance frequently observed following COVID-19.}, } @article {pmid35983269, year = {2022}, author = {Fischer, A and Zhang, L and Elbéji, A and Wilmes, P and Oustric, P and Staub, T and Nazarov, PV and Ollert, M and Fagherazzi, G}, title = {Long COVID Symptomatology After 12 Months and Its Impact on Quality of Life According to Initial Coronavirus Disease 2019 Disease Severity.}, journal = {Open forum infectious diseases}, volume = {9}, number = {8}, pages = {ofac397}, pmid = {35983269}, issn = {2328-8957}, abstract = {BACKGROUND: "Long COVID" is characterized by a variety of symptoms and an important burden for affected people. Our objective was to describe long COVID symptomatology according to initial coronavirus disease 2019 (COVID-19) severity.

METHODS: Predi-COVID cohort study participants, recruited at the time of acute COVID-19 infection, completed a detailed 12-month symptom and quality of life questionnaire. Frequencies and co-occurrences of symptoms were assessed.

RESULTS: Among the 289 participants who fully completed the 12-month questionnaire, 59.5% reported at least 1 symptom, with a median of 6 symptoms. Participants with an initial moderate or severe acute illness declared more frequently 1 or more symptoms (82.6% vs 38.6%, P < .001) and had on average 6.8 more symptoms (95% confidence interval, 4.18-9.38) than initially asymptomatic participants who developed symptoms after the acute infection. Overall, 12.5% of the participants could not envisage coping with their symptoms in the long term. Frequently reported symptoms, such as neurological and cardiovascular symptoms, but also less frequent ones such as gastrointestinal symptoms, tended to cluster.

CONCLUSIONS: Frequencies and burden of symptoms present 12 months after acute COVID-19 infection increased with the severity of the acute illness. Long COVID likely consists of multiple subcategories rather than a single entity. This work will contribute to the better understanding of long COVID and to the definition of precision health strategies.

CLINICAL TRIALS REGISTRATION: NCT04380987.}, } @article {pmid35983089, year = {2022}, author = {Ito, A and Okada, T and Minato, N and Hattori, F}, title = {Possible internal viral shedding and interferon production after clinical recovery from COVID-19: Case report.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {959196}, pmid = {35983089}, issn = {2296-858X}, abstract = {A 70-year-old man underwent off-pump coronary artery bypass grafting 28 days after his recovery from coronavirus disease 2019 (COVID-19), which was confirmed by a negative polymerase chain reaction (PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a nasopharyngeal swab. The PCR test result was also negative for nasopharyngeal sampling 5 days prior to the surgery. However, his redundant saphenous vein and sputum through the endotracheal tube that was taken on the operative day showed the presence of SARS-CoV-2 by PCR. Immunohistochemical analysis of Spike and Nucleoprotein of the saphenous vein showed small clusters of each antigen-positive speckle. Ultrastructural imaging of the saphenous vein showed virus-like particles. The cell-based assay suggested that the patient's serum contained a higher concentration of type-I interferons than that of healthy control sera. These observations suggest that internal viral shedding and, to some extent, innate immune responses continue after COVID-19 recovery.}, } @article {pmid35982674, year = {2022}, author = {Demko, ZO and Yu, T and Mullapudi, SK and Varela Heslin, MG and Dorsey, CA and Payton, CB and Tornheim, JA and Blair, PW and Mehta, SH and Thomas, DL and Manabe, YC and Antar, AAR and , }, title = {Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.08.08.22278543}, pmid = {35982674}, support = {K08 AI143391/AI/NIAID NIH HHS/United States ; K23 AI135102/AI/NIAID NIH HHS/United States ; }, abstract = {Little data exist on long COVID outcomes beyond one year. In a cohort enrolled with mild-moderate acute COVID-19, a wide range of symptoms manifest at 6, 12, and 18 months. Endorsing over 3 symptoms associates with poorer quality of life in 5 domains: physical, social, fatigue, pain, and general health.}, } @article {pmid35982667, year = {2022}, author = {Klein, J and Wood, J and Jaycox, J and Lu, P and Dhodapkar, RM and Gehlhausen, JR and Tabachnikova, A and Tabacof, L and Malik, AA and Kamath, K and Greene, K and Monteiro, VS and Peña-Hernandez, M and Mao, T and Bhattacharjee, B and Takahashi, T and Lucas, C and Silva, J and Mccarthy, D and Breyman, E and Tosto-Mancuso, J and Dai, Y and Perotti, E and Akduman, K and Tzeng, TJ and Xu, L and Yildirim, I and Krumholz, HM and Shon, J and Medzhitov, R and Omer, SB and van Dijk, D and Ring, AM and Putrino, D and Iwasaki, A}, title = {Distinguishing features of Long COVID identified through immune profiling.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.08.09.22278592}, pmid = {35982667}, support = {R01 AI157488/AI/NIAID NIH HHS/United States ; T32 AI007019/AI/NIAID NIH HHS/United States ; }, abstract = {SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID [1-3] . Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions [1-3] ; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.}, } @article {pmid35981692, year = {2022}, author = {Zhou, Y and Liu, X and Wang, X and Li, H and Zeng, G}, title = {Re: 'Association between IgG antibody levels and adverse events after first and second BNT162b2 mRNA vaccine doses' by Braun et al.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {12}, pages = {1671-1672}, pmid = {35981692}, issn = {1469-0691}, mesh = {Humans ; *Immunoglobulin G ; *BNT162 Vaccine ; Vaccines, Synthetic ; Antibodies, Viral ; mRNA Vaccines ; }, } @article {pmid35981646, year = {2022}, author = {Goetzl, EJ and Kapogiannis, D}, title = {Long-COVID: Phase 2 of the COVID-19 Pandemic.}, journal = {The American journal of medicine}, volume = {135}, number = {11}, pages = {1277-1279}, pmid = {35981646}, issn = {1555-7162}, mesh = {Humans ; *COVID-19/complications/epidemiology ; Pandemics ; *Post-Acute COVID-19 Syndrome/epidemiology ; SARS-CoV-2 ; }, } @article {pmid35981059, year = {2022}, author = {Kalimuddin, S and Teh, YE and Wee, LE and Paintal, S and Sasisekharan, R and Low, JG and Sheth, SK and Ooi, EE}, title = {Chronic sequelae complicate convalescence from both dengue and acute viral respiratory illness.}, journal = {PLoS neglected tropical diseases}, volume = {16}, number = {8}, pages = {e0010724}, pmid = {35981059}, issn = {1935-2735}, mesh = {*COVID-19/complications ; Convalescence ; *Dengue/complications/epidemiology ; Disease Progression ; Humans ; Male ; Pandemics ; *Respiratory Tract Infections/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long Covid has raised awareness of the potentially disabling chronic sequelae that afflicts patients after acute viral infection. Similar syndromes of post-infectious sequelae have also been observed after other viral infections such as dengue, but their true prevalence and functional impact remain poorly defined. We prospectively enrolled 209 patients with acute dengue (n = 48; one with severe dengue) and other acute viral respiratory infections (ARI) (n = 161), and followed them up for chronic sequelae up to one year post-enrolment, prior to the onset of the Covid-19 pandemic. Baseline demographics and co-morbidities were balanced between both groups except for gender, with more males in the dengue cohort (63% vs 29%, p<0.001). Except for the first visit, data on symptoms were collected remotely using a purpose-built mobile phone application. Mental health outcomes were evaluated using the validated SF-12v2 Health Survey. Almost all patients (95.8% of dengue and 94.4% of ARI patients) experienced at least one symptom of fatigue, somnolence, headache, concentration impairment or memory impairment within the first week of enrolment. Amongst patients with at least 3-months of follow-up, 18.0% in the dengue cohort and 14.6% in the ARI cohort experienced persistent symptoms. The median month-3 SF-12v2 Mental Component Summary Score was lower in patients who remained symptomatic at 3 months and beyond, compared to those whose symptoms fully resolved (47.7 vs. 56.0, p<0.001), indicating that patients who self-reported persistence of symptoms also experienced functionally worse mental health. No statistically significant difference in age, gender distribution or hospitalisation status was observed between those with and without chronic sequelae. Our findings reveal an under-appreciated burden of post-infection chronic sequelae in dengue and ARI patients. They call for studies to define the pathophysiology of this condition, and determine the efficacy of both vaccines as well as antiviral drugs in preventing such sequelae.}, } @article {pmid35981036, year = {2022}, author = {Couzin-Frankel, J}, title = {Long Covid clues emerge from patients' blood.}, journal = {Science (New York, N.Y.)}, volume = {377}, number = {6608}, pages = {803}, doi = {10.1126/science.ade4427}, pmid = {35981036}, issn = {1095-9203}, mesh = {*COVID-19/blood/immunology ; Humans ; Hydrocortisone/blood ; T-Lymphocytes/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Study implicates lack of key hormone, battle-weary immune cells, and awakened viruses.}, } @article {pmid35979616, year = {2023}, author = {Ehikhametalor, K and Deans-Minott, J and Duncan, JP}, title = {Multisystem Inflammatory Syndrome in Adults (MIS-A) After COVID-19 Infection and Recent Vaccination with Recombinant Adenoviral Vector Encoding the Spike Protein Antigen of SARS-CoV-2 (ChAdOx1 nCoV-19, Vaxzevria).}, journal = {Journal of intensive care medicine}, volume = {38}, number = {2}, pages = {232-237}, pmid = {35979616}, issn = {1525-1489}, mesh = {Adult ; Humans ; ChAdOx1 nCoV-19 ; *COVID-19 ; COVID-19 Vaccines ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; }, abstract = {The clinical spectrum of Coronavirus 2019 (COVID-19) includes acute COVID-19, long covid and multisystem inflammatory syndrome in children and adults (MISC/A). The rapid roll-out of COVID-19 vaccination has the potential to affect the clinical presentation of COVID-19 and case reports document rare occurrences of MIS-A after COVID-19 infection and recent vaccination with m-RNA vaccines. We describe 2 cases of MIS-A after COVID-19 infection and recent vaccination with ChAdOx1 nCoV-19.}, } @article {pmid35976326, year = {2022}, author = {Guedes, BF}, title = {NeuroCOVID-19: a critical review.}, journal = {Arquivos de neuro-psiquiatria}, volume = {80}, number = {5 Suppl 1}, pages = {281-289}, pmid = {35976326}, issn = {1678-4227}, mesh = {*COVID-19/complications ; Humans ; *Nervous System Diseases/diagnosis ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon.

OBJECTIVE: This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge.

METHODS: Narrative review.

RESULTS: Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists.

CONCLUSION: Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword - putting patient's suffering in the spotlight, but with a tradeoff in methodological consistency.}, } @article {pmid35974973, year = {2022}, author = {Banerjee, I and Robinson, J and Leclézio, A and Sathian, B and Banerjee, I}, title = {Post COVID syndrome: A novel challenge and threat to international health.}, journal = {Nepal journal of epidemiology}, volume = {12}, number = {2}, pages = {1215-1219}, pmid = {35974973}, issn = {2091-0800}, abstract = {The global pandemic caused by the SARS-CoV-2 virus has affected every continent worldwide. The novelty of this virus, its mutations and the rapid speed and unprecedented rate at which it has torn through the global community has in turn lead to an innate lack of knowledge and information about the actual disease caused and the severity of the complications associated with COVID-19. The SARS-CoV-2 virus has been infecting individuals since 2019 and now as of 2022 has been circulating for just over 2 years within the global populous. As the number of cases have risen globally over this period (some of which having contracted the virus twice) further endeavours have been undertaken to better understand the pathogenesis and natural progression of the disease. A condition reported in some cases with extended bouts of sickness or symptoms following the initial infection with COVID was labelled "long COVID" towards the earlier phases of the pandemic (in the spring of 2020), but has only recently gained the global media and medical attention due to its affliction of more individuals on a global basis and has thus warranted further investigation. Long COVID is described as a persistent, long-term state of poor health following an infection with COVID-19. The effect of Long COVID is multisystemic in nature with a wide array of signs and symptoms. The most commonly reported clinical features of long COVID are: headaches, myalgia, chest pain, rashes, abdominal pain, shortness of breath, palpitations, anosmia, persistent cough, brain fogs, forgetfulness, depression, insomnia, fatigue and anxiety. This research aims to explore the symptomatology, pathophysiology as well as the treatment and prevention of Long COVID.}, } @article {pmid35974260, year = {2023}, author = {Malahfji, M and Crudo, V and Ahmed, AI and Saeed, M and Saad, JM and Zoghbi, WA and Al-Mallah, MH}, title = {Coronary microvascular dysfunction and COVID-19: implications for long COVID patients.}, journal = {Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology}, volume = {30}, number = {5}, pages = {2204-2206}, pmid = {35974260}, issn = {1532-6551}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Coronary Artery Disease/diagnostic imaging ; *Myocardial Ischemia ; Coronary Vessels ; Microcirculation ; Coronary Circulation ; }, } @article {pmid35974081, year = {2022}, author = {Pérez-González, A and Araújo-Ameijeiras, A and Fernández-Villar, A and Crespo, M and Poveda, E and , }, title = {Author Correction: Long COVID in hospitalized and non-hospitalized patients in a large cohort in Northwest Spain, a prospective cohort study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {13873}, doi = {10.1038/s41598-022-18023-z}, pmid = {35974081}, issn = {2045-2322}, } @article {pmid35971552, year = {2022}, author = {Kaushik, A and Mostafavi, E}, title = {To manage long COVID by selective SARS-CoV-2 infection biosensing.}, journal = {Innovation (Cambridge (Mass.))}, volume = {3}, number = {5}, pages = {100303}, pmid = {35971552}, issn = {2666-6758}, support = {T32 EB009035/EB/NIBIB NIH HHS/United States ; }, } @article {pmid35971463, year = {2022}, author = {Azadvari, M and Haghparast, A and Nakhostin-Ansari, A and Emami Razavi, SZ and Hosseini, M}, title = {Musculoskeletal symptoms in patients with long COVID: A cross-sectional study on Iranian patients.}, journal = {Heliyon}, volume = {8}, number = {8}, pages = {e10148}, pmid = {35971463}, issn = {2405-8440}, abstract = {BACKGROUND AND OBJECTIVES: Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors.

METHODS: We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants' demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients' characteristic and COVID-19 course was evaluated.

RESULT: 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD = 11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms.

CONCLUSION: This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.}, } @article {pmid35971155, year = {2022}, author = {Morrow, A and Gray, SR and Bayes, HK and Sykes, R and McGarry, E and Anderson, D and Boiskin, D and Burke, C and Cleland, JGF and Goodyear, C and Ibbotson, T and Lang, CC and McConnachie, and Mair, F and Mangion, K and Patel, M and Sattar, N and Taggart, D and Taylor, R and Dawkes, S and Berry, C}, title = {Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.}, journal = {Trials}, volume = {23}, number = {1}, pages = {660}, pmid = {35971155}, issn = {1745-6215}, support = {COV/LTE/20/10/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Adult ; COVID-19/*complications/therapy ; Chest Pain ; Dyspnea ; Fatigue ; Humans ; Quality of Life ; *Resistance Training ; *SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection.

METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea.

DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals.

TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.}, } @article {pmid35971066, year = {2022}, author = {Dahmen, A and Keller, FM and Derksen, C and Rinn, R and Becker, P and Lippke, S}, title = {Screening and assessment for post-acute COVID-19 syndrome (PACS), guidance by personal pilots and support with individual digital trainings within intersectoral care: a study protocol of a randomized controlled trial.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {693}, pmid = {35971066}, issn = {1471-2334}, support = {Gesamt-2490-PC-2021-V7- D56613/2021//Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit/ ; }, mesh = {*COVID-19/complications ; Humans ; Mass Screening ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Because the clinical patterns and symptoms that persist after a COVID-19 infection are diverse, a diagnosis of post-acute COVID-19 syndrome (PACS) is difficult to implement. The current research project therefore aims to evaluate the feasibility and the practicability of a comprehensive, interdisciplinary, and cross-sectoral treatment program consisting of a low-threshold online screening and holistic assessment for PACS. Furthermore, it aims to evaluate digital interventions and the use of so-called personal guides that may help to facilitate the recovery of PACS.

METHODS: This German study consists of a low-threshold online screening for PACS where positively screened participants will be supported throughout by personal pilots. The personal pilots are aimed at empowering patients and helping them to navigate through the study and different treatment options. Patients will then be randomly assigned either to an intervention group (IG) or an active control group (ACG). The IG will receive a comprehensive assessment of physiological and psychological functioning to inform future treatment. The ACG does not receive the assessment but both groups will receive a treatment consisting of an individual digital treatment program (digital intervention platform and an intervention via a chatbot). This digital intervention is based on the needs identified during the assessment for participants in the IG. Compared to that, the ACG will receive a more common digital treatment program aiming to reduce PACS symptoms. Importantly, a third comparison group (CompG) will be recruited that does not receive any treatment. A propensity score matching will take place, ensuring comparability between the participants. Primary endpoints of the study are symptom reduction and return to work. Secondary outcomes comprise, for example, social participation and activities in daily life. Furthermore, the feasibility and applicability of the online screening tool, the holistic assessment, digital trainings, and personal pilots will be evaluated.

DISCUSSION: This is one of the first large-scale studies to improve the diagnosis and the care of patients with PACS by means of empowerment. It is to be evaluated whether the methods utilized can be used for the German and international population. Trial registration ClinicalTrials.gov Identifier: NCT05238415; date of registration: February 14, 2022.}, } @article {pmid35970935, year = {2023}, author = {Nathanielsz, J and Toh, ZQ and Do, LAH and Mulholland, K and Licciardi, PV}, title = {SARS-CoV-2 infection in children and implications for vaccination.}, journal = {Pediatric research}, volume = {93}, number = {5}, pages = {1177-1187}, pmid = {35970935}, issn = {1530-0447}, mesh = {Adolescent ; Adult ; Humans ; Child ; *COVID-19/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Pandemics ; Vaccination ; }, abstract = {The COVID-19 pandemic caused by novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for more than 500 million cases worldwide as of April 2022. Initial estimates in 2020 found that children were less likely to become infected with SARS-CoV-2 and more likely to be asymptomatic or display mild COVID-19 symptoms. Our early understanding of COVID-19 transmission and disease in children led to a range of public health measures including school closures that have indirectly impacted child health and wellbeing. The emergence of variants of concern (particularly Delta and Omicron) has raised new issues about transmissibility in children, as preliminary data suggest that children may be at increased risk of infection, especially if unvaccinated. Global national prevalence data show that SARS-CoV-2 infection in children and adolescents is rising due to COVID-19 vaccination among adults and increased circulation of Delta and Omicron variants. To mitigate this, childhood immunisation programmes are being implemented globally to prevent direct and indirect consequences of COVID-19 including severe complications (e.g., MIS-C), debilitating long-COVID symptoms, and the indirect impacts of prolonged community and school closures on childhood education, social and behavioural development and mental health. This review explores the current state of knowledge on COVID-19 in children including COVID-19 vaccination strategies. IMPACT: Provides an up-to-date account of SARS-CoV-2 infections in children. Discusses the direct and indirect effects of COVID-19 in children. Provides the latest information on the current state of global COVID-19 vaccination in children.}, } @article {pmid35969597, year = {2022}, author = {Ramasawmy, M and Mu, Y and Clutterbuck, D and Pantelic, M and Lip, GYH and van der Feltz-Cornelis, C and Wootton, D and Williams, NH and Montgomery, H and Mallinson Cookson, R and Attree, E and Gabbay, M and Heightman, M and Alwan, NA and Banerjee, A and Lorgelly, P and , }, title = {STIMULATE-ICP-CAREINEQUAL (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) study protocol: Defining usual care and examining inequalities in Long Covid support.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0271978}, pmid = {35969597}, issn = {1932-6203}, support = {COV-LT2-0043/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/therapy ; Critical Pathways ; *Delivery of Health Care, Integrated ; Humans ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Individuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor. In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients' experiences of stigma and discrimination.

METHODS AND ANALYSIS: A mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received.

ETHICS AND DISSEMINATION: Ethical approval was obtained from South Central-Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.}, } @article {pmid35968657, year = {2024}, author = {Lunt, J and Hemming, S and Burton, K and Elander, J and Baraniak, A}, title = {What workers can tell us about post-COVID workability.}, journal = {Occupational medicine (Oxford, England)}, volume = {74}, number = {1}, pages = {15-23}, pmid = {35968657}, issn = {1471-8405}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; Workplace/psychology ; *Occupational Health ; Social Support ; }, abstract = {BACKGROUND: The apparent functional impact of post-COVID-19 syndrome has workability implications for large segments of the working-age population.

AIMS: To understand obstacles and enablers around self-reported workability of workers following COVID-19, to better guide sustainable workplace accommodations.

METHODS: An exploratory online survey comprising quantitative and qualitative questions was disseminated via social media and industry networks between December 2020 and February 2021, yielding usable responses from 145 workers. Qualitative data were subjected to content analysis.

RESULTS: Over half of the sample (64%) were from the health, social care, and education sectors. Just under 15% had returned to work, and 53% and 50% reported their physical and psychological workability respectively as moderate at best. Leading workability obstacles were multi-level, comprising fatigue, the interaction between symptoms and job, lack of control over job pressures, inappropriate sickness absence management policies, and lack of COVID-aware organizational cultures. Self-management support, modified work, flexible co-developed graded return-to-work planning, and improved line management competency were advocated as key enablers.

CONCLUSIONS: Assuming appropriate medical management of any pathophysiological complications of COVID-19, maintaining or regaining post-COVID workability might reasonably follow a typical biopsychosocial framework enhanced to cater to the fluctuating nature of the symptoms. This should entail flexible, regularly reviewed and longer-term return-to-work planning addressing multi-level workability obstacles, co-developed between workers and line managers, with support from human resources, occupational health professionals (OHP's), and a COVID-aware organizational culture.}, } @article {pmid35966751, year = {2022}, author = {Kim, TH and Jeon, SR and Kang, JW and Kwon, S}, title = {Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2022}, number = {}, pages = {7303393}, pmid = {35966751}, issn = {1741-427X}, abstract = {Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis. The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications. The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.}, } @article {pmid35966512, year = {2022}, author = {Motloch, LJ and Jirak, P and Mirna, M and Fiedler, L and Davtyan, PA and Lakman, IA and Gareeva, DF and Tyurin, AV and Gumerov, RM and Matskeplishvili, ST and Pavlov, VN and Cai, B and Kopp, K and Topf, A and Hoppe, UC and Pistulli, R and Zagidullin, NS}, title = {Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {916156}, pmid = {35966512}, issn = {2297-055X}, abstract = {INTRODUCTION: Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting.

METHODS: To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period.

RESULTS: While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = -3.33 (0.60), P < 0.001 and dipyridamole: B = -3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = -2.69 (0.74), P < 0.001 and dipyridamole: B = -17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B-3.12 (1.42), P = 0.012] and stroke [B = -3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = -17.05 (1.01), P < 0.001].

CONCLUSION: Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.}, } @article {pmid35966226, year = {2022}, author = {Jukema, BN and Smit, K and Hopman, MTE and Bongers, CCWG and Pelgrim, TC and Rijk, MH and Platteel, TN and Venekamp, RP and Zwart, DLM and Rutten, FH and Koenderman, L}, title = {Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease.}, journal = {Frontiers in allergy}, volume = {3}, number = {}, pages = {942699}, pmid = {35966226}, issn = {2673-6101}, abstract = {INTRODUCTION: Neutrophil and eosinophil activation and its relation to disease severity has been understudied in primary care patients with COVID-19. In this study, we investigated whether the neutrophil and eosinophil compartment were affected in primary care patients with COVID-19.

METHODS: COVID-19 patients, aged ≥ 40 years with cardiovascular comorbidity presenting to the general practitioner with substantial symptoms, partaking in the COVIDSat@Home study between January and April 2021, were included. Blood was drawn during and 3 to 6 months after active COVID-19 disease and analyzed by automated flow cytometry, before and after stimulation with a formyl-peptide (fNLF). Mature neutrophil and eosinophil markers at both time points were compared to healthy controls. A questionnaire was conducted on disease symptoms during and 3 to 6 months after COVID-19 disease.

RESULTS: The blood of 18 COVID-19 patients and 34 healthy controls was analyzed. During active COVID-19 disease, neutrophils showed reduced CD10 (p = 0.0360), increased CD11b (p = 0.0002) and decreased CD62L expression (p < 0.0001) compared to healthy controls. During active COVID-19 disease, fNLF stimulated neutrophils showed decreased CD10 levels (p < 0.0001). Three to six months after COVID-19 disease, unstimulated neutrophils showed lowered CD62L expression (p = 0.0003) and stimulated neutrophils had decreased CD10 expression (p = 0.0483) compared to healthy controls. Both (un)stimulated CD10 levels increased 3 to 6 months after active disease (p = 0.0120 and p < 0.0001, respectively) compared to during active disease. Eosinophil blood counts were reduced during active COVID-19 disease and increased 3 to 6 months after infection (p < 0.0001). During active COVID-19, eosinophils showed increased unstimulated CD11b (p = 0.0139) and decreased (un)stimulated CD62L expression (p = 0.0036 and p = 0.0156, respectively) compared to healthy controls. Three to six months after COVID-19 disease, (un)stimulated eosinophil CD62L expression was decreased (p = 0.0148 and p = 0.0063, respectively) and the percentage of CD11b[bright] cells was increased (p = 0.0083 and p = 0.0307, respectively) compared to healthy controls.

CONCLUSION: Automated flow cytometry analysis reveals specific mature neutrophil and eosinophil activation patterns in primary care patients with COVID-19 disease, during and 3 to 6 months after active disease. This suggests that the neutrophil and eosinophil compartment are long-term affected by COVID-19 in primary care patients. This indicates that these compartments may be involved in the pathogenesis of long COVID.}, } @article {pmid35963844, year = {2022}, author = {Florentino, PTV and Alves, FJO and Cerqueira-Silva, T and Oliveira, VA and Júnior, JBS and Jantsch, AG and Penna, GO and Boaventura, V and Werneck, GL and Rodrigues, LC and Pearce, N and Barral-Netto, M and Barreto, ML and Paixão, ES}, title = {Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {4756}, pmid = {35963844}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 213589/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Brazil/epidemiology ; *COVID-19/complications/epidemiology/prevention & control ; Case-Control Studies ; Child ; Humans ; Systemic Inflammatory Response Syndrome ; Vaccine Efficacy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although severe COVID-19 in children is rare, they may develop multisystem inflammatory syndrome, long-COVID and downstream effects of COVID-19, including social isolation and disruption of education. Data on the effectiveness of the CoronaVac vaccine is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. We conducted a test-negative design to estimate vaccine effectiveness using 197,958 tests from January 21, 2022, to April 15, 2022, during the Omicron dominant period in Brazil among children aged 6 to 11 years. The estimated vaccine effectiveness for symptomatic infection was 39.8% (95% CI 33.7-45.4) at ≥14 days post-second dose. For hospital admission vaccine effectiveness was 59.2% (95% CI 11.3-84.5) at ≥14 days. Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness.}, } @article {pmid35963600, year = {2022}, author = {Morioka, S and Tsuzuki, S and Suzuki, M and Terada, M and Akashi, M and Osanai, Y and Kuge, C and Sanada, M and Tanaka, K and Maruki, T and Takahashi, K and Saito, S and Hayakawa, K and Teruya, K and Hojo, M and Ohmagari, N}, title = {Post COVID-19 condition of the Omicron variant of SARS-CoV-2.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {28}, number = {11}, pages = {1546-1551}, pmid = {35963600}, issn = {1437-7780}, mesh = {Aged ; *COVID-19/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Quality of Life ; *SARS-CoV-2 ; }, abstract = {OBJECTIVES: To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains.

STUDY DESIGN: A single-center cross-sectional study.

METHODS: Patients who recovered from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients' characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching.

RESULTS: We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively.

CONCLUSIONS: The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.}, } @article {pmid35963198, year = {2022}, author = {Lucchese, G and Vogelgesang, A and Boesl, F and Raafat, D and Holtfreter, S and Bröker, BM and Stufano, A and Fleischmann, R and Prüss, H and Franke, C and Flöel, A}, title = {Anti-neuronal antibodies against brainstem antigens are associated with COVID-19.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104211}, pmid = {35963198}, issn = {2352-3964}, mesh = {Antibodies, Viral ; Brain Stem ; *COVID-19/complications ; Epitopes ; Humans ; Immunoglobulin G ; Immunoglobulin M ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Understanding how SARS-CoV-2 affects respiratory centres in the brainstem may help to preclude assisted ventilation for patients in intensive care setting. Viral invasion appears unlikely, although autoimmunity has been implicated, the responsible antigens remain unknown. We previously predicted the involvement of three epitopes within distinct brainstem proteins: disabled homolog 1 (DAB1), apoptosis-inducing-factor-1 (AIFM1), and surfeit-locus-protein-1 (SURF1).

METHODS: Here, we used microarrays to screen serum from COVID-19 patients admitted to intensive care and compared those with controls who experienced mild course of the disease.

FINDINGS: The results confirm the occurrence of IgG and IgM antibodies against the hypothesised epitopes in COVID-19 patients. Importantly, while IgM levels were similar in both groups, IgG levels were significantly elevated in severely ill patients compared to controls, suggesting a pathogenic role of IgG.

INTERPRETATION: The newly discovered anti-neuronal antibodies might be promising markers of severe disease and the targeted peptide epitopes might be used for targeted immunomodulation. Further work is needed to determine whether these antibodies may play a role in long-COVID.

FUNDING: AF, CF and PR received support from the German Research Foundation (grants FL 379/22-1, 327654276-SFB 1315, FR 4479/1-1, PR 1274/8-1). SH, DR, and DB received support from the Ministry of Economy, State of Mecklenburg Western Pomerania, Germany (grant COVIDPROTECT: "Optimisation of diagnostic and therapeutic pathways for COVID-19 patients in MV"). SH received support from the Research Group Molecular Medicine University of Greifswald (FVMM, seed funding FOVB-2021-01). AV received support from the Else Kröner Fresenius Foundation and the Alzheimer Research Initiative.}, } @article {pmid35962520, year = {2023}, author = {Taghrir, MH and Akbarialiabad, H and Abdollahi, A and Ghahramani, N and Bastani, B and Paydar, S and Razani, B and Mwangi, J and Asadi-Pooya, AA and Roozbeh, J and Malekmakan, L and Kumar, M}, title = {Inequity and disparities mar existing global research evidence on Long COVID.}, journal = {Global health promotion}, volume = {30}, number = {1}, pages = {63-67}, pmid = {35962520}, issn = {1757-9767}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19/epidemiology ; RNA, Viral ; SARS-CoV-2 ; Geography ; }, abstract = {Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead. With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.}, } @article {pmid35962348, year = {2022}, author = {Magdy, R and Elmazny, A and Soliman, SH and Elsebaie, EH and Ali, SH and Abdel Fattah, AM and Hassan, M and Yassien, A and Mahfouz, NA and Elsayed, RM and Fathy, W and Abdel-Hamid, HM and Mohamed, J and Hussein, M}, title = {Post-COVID-19 neuropsychiatric manifestations among COVID-19 survivors suffering from migraine: a case-control study.}, journal = {The journal of headache and pain}, volume = {23}, number = {1}, pages = {101}, pmid = {35962348}, issn = {1129-2377}, mesh = {*COVID-19/complications ; Case-Control Studies ; Headache/epidemiology/etiology ; Humans ; *Migraine Disorders ; SARS-CoV-2 ; Survivors ; }, abstract = {BACKGROUND: The burden of post-coronavirus disease (COVID)-19 symptoms has been increasing and is of great concern in patients with pre-existing chronic medical conditions.This study aimed to delineate the post-COVID-19 neuropsychiatric symptoms among migraine patients compared to the non-migraine control group.

METHODS: Two groups, each of 204 COVID-19 survivors, were enrolled in the study after 3 months of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, one group fulfilling the episodic migraine criteria and the other serving as a matching control group. Subjects were evaluated through an in-person interview for post-COVID-19 neuropsychiatric symptoms, including detailed headache patterns and severity, using the visual analogue scale.

RESULTS: The Frequency of headache during the acute phase of COVID-19 was more frequent in migraine patients (OR = 1.60, 95%CI = 1.04-2.45, P-value = 0.031). The reported significant post-COVID-19 neuropsychiatric symptoms in migraine patients compared to controls were fatigue (OR = 1.662, 95%CI = 1.064-2.596, P-value = 0.025), anosmia/hyposmia (OR = 2.06, 95%CI = 1.164- 3.645, P-value = 0.012), cacosmia (OR = 2.663, 95%CI = 1.145-6.195, P-value = 0.019), depression (OR = 2.259, 95%CI = 1.284- 3.975, P-value = 0.004), anxiety (OR = 3.267, 95%CI = 1.747- 6.108, P-value ≤ 0.001), insomnia (OR = 2.203, 95%CI = 1.298- 3.739, P-value = 0.003), and headache (OR = 3.148, 95%CI = 1.616-6.136, P-value =  ≤ 0.001).While there was no statistically significant difference between migraine patients and controls regarding the post-COVID-19 functional status score (P-value = 0.102). The pattern of post-COVID-19 headache was reported as chronic headache transformation in 17.6% of the migraine group, with the median intensity rate being 5.5 and IQR (3-7). In the control group, 14% experienced chronic headache attributed to systemic viral infection with a median intensity rate of 2 and IQR (2-5), while 12% experienced a new daily persistent headache with a median intensity of 5 and IQR (1-6).

CONCLUSION: The study highlighted the importance of follow-up migraine patients upon recovery from COVID-19 infection, being more vulnerable to post-COVID-19 symptoms.}, } @article {pmid35962207, year = {2022}, author = {}, title = {Long COVID includes breathing and reproductive problems and has a range of risk factors.}, journal = {Nature medicine}, volume = {28}, number = {8}, pages = {1554-1555}, pmid = {35962207}, issn = {1546-170X}, mesh = {*COVID-19/complications/epidemiology ; Data Collection ; Humans ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {A large cohort of non-hospitalized adults with confirmed SARS-CoV-2 infection and matched controls were studied to investigate the symptoms of long COVID. SARS-CoV-2 infection was associated with 62 symptoms (three clusters) that persisted beyond 12 weeks, and with a range of risk factors.}, } @article {pmid35960527, year = {2022}, author = {Abbasi, J}, title = {The US Now Has a Research Plan for Long COVID-Is It Enough?.}, journal = {JAMA}, volume = {328}, number = {9}, pages = {812-814}, doi = {10.1001/jama.2022.14536}, pmid = {35960527}, issn = {1538-3598}, mesh = {*Biomedical Research/organization & administration ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; United States ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35959897, year = {2023}, author = {Fjelltveit, EB and Blomberg, B and Kuwelker, K and Zhou, F and Onyango, TB and Brokstad, KA and Elyanow, R and Kaplan, IM and Tøndel, C and Mohn, KGI and Özgümüş, T and Cox, RJ and Langeland, N and , }, title = {Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {3}, pages = {e60-e70}, pmid = {35959897}, issn = {1537-6591}, support = {101563/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Female ; Humans ; *SARS-CoV-2 ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Case-Control Studies ; Dyspnea ; Memory Disorders ; }, abstract = {BACKGROUND: The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID.

METHODS: A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses.

RESULTS: Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27-10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51-15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88-20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22-5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5-21.5; P = .024) and among women (excess risk 18.7%; 95% CI, 4.4-32.9; P = .010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor β depth was significantly associated with both dyspnea and number of symptoms at 12 months.

CONCLUSIONS: This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms.}, } @article {pmid35958855, year = {2022}, author = {Zhang, Q and Li, J and Weng, L}, title = {A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {937008}, pmid = {35958855}, issn = {2296-2565}, mesh = {Bibliometrics ; *COVID-19/complications ; Child ; Humans ; Iran ; Pandemics ; SARS-CoV-2 ; United States ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The characteristic symptom of coronavirus disease 2019 (COVID-19) is respiratory distress, but neurological symptoms are the most frequent extra-pulmonary symptoms. This study aims to explore the current status and hot topics of neurology-related research on COVID-19 using bibliometric analysis.

METHODS: Publications regarding neurology and COVID-19 were retrieved from the Web of Science Core Collection (WoSCC) on March 28 2022. The Advanced search was conducted using "TS = ('COVID 19' or 'Novel Coronavirus 2019' or 'Coronavirus disease 2019' or '2019-nCOV' or 'SARS-CoV-2' or 'coronavirus-2') and TS = ('neurology'or 'neurological' or 'nervous system' or 'neurodegenerative disease' or 'brain' or 'cerebra' or 'nerve')". Microsoft Excel 2010 and VOSviewer were used to characterize the largest contributors, including the authors, journals, institutions, and countries. The hot topics and knowledge network were analyzed by CiteSpace and VOSviewer.

RESULTS: A total of 5,329 publications between 2020 and 2022 were retrieved. The United States, Italy, and the United Kingdom were three key contributors to this field. Harvard Medical School, the Tehran University of Medical Sciences, and the UCL Queen Square Institute of Neurology were the major institutions with the largest publications. Josef Finsterer from the University of São Paulo (Austria) was the most prolific author. Tom Solomon from the University of Liverpool (UK) was the most cited author. Neurological Sciences and Frontiers in Neurology were the first two most productive journals, while Journal of Neurology held the first in terms of total citations and citations per publication. Cerebrovascular diseases, neurodegenerative diseases, encephalitis and encephalopathy, neuroimmune complications, neurological presentation in children, long COVID and mental health, and telemedicine were the central topics regarding the neurology-related research on COVID-19.

CONCLUSION: Neurology-related research on COVID-19 has attracted considerable attention worldwide. Research topics shifted from "morality, autopsy, and telemedicine" in 2020 to various COVID-19-related neurological symptoms in 2021, such as "stroke," "Alzheimer's disease," "Parkinson's disease," "Guillain-Barre syndrome," "multiple sclerosis," "seizures in children," and "long COVID." "Applications of telemedicine in neurology during COVID-19 pandemic," "COVID-19-related neurological complications and mechanism," and "long COVID" require further study.}, } @article {pmid35957651, year = {2022}, author = {Sarda, R and Kumar, A and Chandra, A and Bir, M and Kumar, S and Soneja, M and Sinha, S and Wig, N}, title = {Prevalence of Long COVID-19 and its Impact on Quality of Life Among Outpatients With Mild COVID-19 Disease at Tertiary Care Center in North India.}, journal = {Journal of patient experience}, volume = {9}, number = {}, pages = {23743735221117358}, pmid = {35957651}, issn = {2374-3735}, abstract = {Literature is lacking on the spectrum of symptoms of long COVID-19 (defined as symptoms persisting beyond 28 days of diagnosis) and its impact on quality of life. This single-center, cross-sectional study included mild COVID-19 cases as determined by a positive real-time reverse transcription polymerase chain reaction test. Patients were contacted at least 28 days after diagnosis and were interviewed telephonically using semi-structured questionnaires for duration of symptoms, fatigue using Fatigue Severity Scale (FSS) and quality of life using the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). A total of 251 COVID-19 patients were included; of which 169 (67.3%) were males. The mean age of the patients was 35.8 years (SD = 12.5). The prevalence of long COVID-19 was 28.2% (n = 71, 95% CI: 23.0-34.2). The most common symptoms involved the musculoskeletal system (12.7%), upper respiratory tract (7.6%), and fatigue among 17 (6.8%) patients. Patients with long COVID-19 had significantly higher FSS score and lower WHOQOL-BREF score compared to the patients without long COVID-19 (<28 days).}, } @article {pmid35957578, year = {2023}, author = {Gary, JB and Gallagher, L and Joseph, PV and Reed, D and Gudis, DA and Overdevest, JB}, title = {Qualitative Olfactory Dysfunction and COVID-19: An Evidence-Based Review with Recommendations for the Clinician.}, journal = {American journal of rhinology & allergy}, volume = {37}, number = {1}, pages = {95-101}, pmid = {35957578}, issn = {1945-8932}, support = {K23 DC019678/DC/NIDCD NIH HHS/United States ; T35 AG044303/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Anosmia ; *COVID-19/complications/epidemiology ; *Olfaction Disorders/diagnosis/epidemiology/therapy ; Quality of Life ; SARS-CoV-2 ; Smell ; }, abstract = {BACKGROUND: Nearly 40% of patients who experience smell loss during SARS-CoV-2 infection may develop qualitative olfactory dysfunction, most commonly parosmia. Our evidence-based review summarizes the evolving literature and offers recommendations for the clinician on the management of patients experiencing parosmia associated with COVID-19.

METHODS: We performed a systematic search using independent queries in PubMed, Embase, Ovid, and Cochrane databases, then categorized articles according to themes that emerged regarding epidemiology, effect on quality of life, disease progression, prognosis, pathophysiology, diagnosis, and treatment of parosmia.

RESULTS: We identified 123 unique references meeting eligibility and performed title and abstract review with 2 independent reviewers, with 74 articles undergoing full-text review. An inductive approach to thematic development provided 7 central themes regarding qualitative olfactory dysfunction following COVID-19.

CONCLUSIONS: While other respiratory viruses are known to cause qualitative olfactory disturbances, the incidence of parosmia following COVID-19 is notable, and correlates negatively with age. The presence of parosmia predicts persistent quantitative olfactory dysfunction. Onset can occur months after infection, and symptoms may persist for well over 7 months. Affected patients report increased anxiety and decreased quality of life. Structured olfactory training with essential oils is the preferred treatment, where parosmia predicts recovery of aspects of quantitative smell loss when undergoing training. There is limited evidence that nasal corticosteroids may accelerate recovery of olfactory function. Patients should be prepared for the possibility that symptoms may persist for years, and providers should guide them to resources for coping with their psychosocial burden.}, } @article {pmid35956247, year = {2022}, author = {Fernández-de-Las-Peñas, C and Fuensalida-Novo, S and Ortega-Santiago, R and Valera-Calero, JA and Cescon, C and Derboni, M and Giuffrida, V and Barbero, M}, title = {Pain Extent Is Not Associated with Sensory-Associated Symptoms, Cognitive or Psychological Variables in COVID-19 Survivors Suffering from Post-COVID Pain.}, journal = {Journal of clinical medicine}, volume = {11}, number = {15}, pages = {}, pmid = {35956247}, issn = {2077-0383}, support = {LONG COVID EXP//Comunidad de Madrid/ ; 0067235//Novo Nordisk Foundation/ ; }, abstract = {We aimed to investigate the relationship between pain extent, as a sign of sensitization, and sensory-related, cognitive and psychological variables in hospitalized COVID-19 survivors with post-COVID pain. One hundred and forty-six (67 males, 79 females) previously hospitalized COVID-19 survivors with post-COVID pain completed demographic (age, sex, height, weight), sensory-related (Central Sensitization Inventory, Self-Report Leeds Assessment of Neuropathic Symptoms), cognitive (Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia) and psychological (Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index) variables. Pain extent and frequency maps were calculated from pain drawings using customized software. After conducting a correlation analysis to determine the relationships between variables, a stepwise linear regression model was performed to identify pain extent predictors, if available. Pain extent was significantly and weakly associated with pain intensity (r = -0.201, p = 0.014): the larger the pain extent, the lower the pain intensity. No other significant association was observed between pain extent and sensory-related, cognitive, or psychological variables in individuals with post-COVID pain. Females had higher pain intensity, more sensitization-associated symptoms, higher anxiety, lower sleep quality, and higher kinesiophobia levels than males. Sex differences correlation analyses revealed that pain extent was associated with pain intensity in males, but not in females. Pain extent was not associated with any of the measured variables and was also not related to the presence of sensitization-associated symptoms in our sample of COVID-19 survivors with long-term post-COVID pain.}, } @article {pmid35956094, year = {2022}, author = {Grieco, T and Gomes, V and Rossi, A and Cantisani, C and Greco, ME and Rossi, G and Sernicola, A and Pellacani, G}, title = {The Pathological Culprit of Neuropathic Skin Pain in Long COVID-19 Patients: A Case Series.}, journal = {Journal of clinical medicine}, volume = {11}, number = {15}, pages = {}, pmid = {35956094}, issn = {2077-0383}, abstract = {Cutaneous neurosensory symptoms have become increasingly reported findings in COVID-19; however, these virus-related manifestations are largely overlooked, and their pathology is poorly understood. Moreover, alterations of skin sensibility currently recognize no clear histopathology substrate. The purpose of this study was to provide pathology evidence of neurosensory skin system involvement in COVID-19 patients complaining of subjective neurological symptoms affecting the skin. Out of 142 patients, six long COVID-19 cases complaining of cutaneous subjective neurological symptoms assessed on an NTSS-6 questionnaire underwent histopathological and immunohistochemical analyses of skin areas affected by paroxysmal diffuse burning and itching sensations. Two patients also performed electroneurography examination. The histology investigation showed hypertrophic glomus vascular bodies with hypertrophic S100+ perineural sheath cells and adjacent hypertrophy of the nerve branches associated with increased basophil polysaccharide matrix. Electroneurography revealed disturbances of A-delta and C dermal neuronal fibers. The main limitation of this study consisted of a limited number of skin biopsy samples, requiring further investigation. Histopathology findings are consistent with hypertrophy of nerve endings, suggesting a condition such as "dermal hyperneury", a recently reported small nerve hypertrophy condition affecting sensory C fibers. Such a neuropathic basis could explain dysesthesia experienced by the patients, as previously described in postherpetic neuralgia.}, } @article {pmid35956037, year = {2022}, author = {Blumberg, Y and Edelstein, M and Abu Jabal, K and Golan, R and Tuvia, N and Perets, Y and Saad, M and Levinas, T and Saleem, D and Israeli, Z and Alaa, AR and Elbaz Greener, G and Amital, A and Halabi, M}, title = {Protective Effects of BNT162b2 Vaccination on Aerobic Capacity Following Mild to Moderate SARS-CoV-2 Infection: A Cross-Sectional Study Israel.}, journal = {Journal of clinical medicine}, volume = {11}, number = {15}, pages = {}, pmid = {35956037}, issn = {2077-0383}, abstract = {Patients previously infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may experience post-acute adverse health outcomes, known as long COVID. The most reported symptoms are fatigue, headache and attention/concentration issues, dyspnea and myalgia. In addition, reduced aerobic capacity has been demonstrated in both mild and moderate COVID-19 patients. It is unknown whether COVID-19 vaccination mitigates against reduced aerobic capacity. Our aim was to compare the aerobic capacity of vaccinated and unvaccinated individuals previously infected with SARS-CoV-2. Methods: Individuals aged 18 to 65 years with laboratory-confirmed mild to moderate COVID-19 disease were invited to Ziv Medical Centre, Israel, three months after SARS-CoV-2 infection. We compared individuals unvaccinated at the time of infection to those vaccinated in terms of aerobic capacity, measured using symptom-limited cardiopulmonary exercise test (CPET). Results: We recruited 28 unvaccinated and 22 vaccinated patients. There were no differences in baseline demographic and pulmonary function testing (PFT) parameters. Compared with unvaccinated individuals, those vaccinated had higher V’O2/kg at peak exercise and at the anaerobic threshold. The V’O2/kg peak in the unvaccinated group was 83% of predicted vs. 100% in the vaccinated (p < 0.002). At the anaerobic threshold (AT), vaccinated individuals had a higher V’O2/kg than those unvaccinated. Conclusions: Vaccinated individuals had significantly better exercise performance. Compared with vaccinated individuals, a higher proportion of those unvaccinated performed substantially worse than expected on CPET. These results suggest that vaccination at the time of infection is associated with better aerobic capacity following SARS-CoV-2 infection.}, } @article {pmid35955979, year = {2022}, author = {Buonsenso, D and Valentini, P and De Rose, C and Tredicine, M and Pereyra Boza, MDC and Camponeschi, C and Morello, R and Zampino, G and Brooks, AES and Rende, M and Ria, F and Sanguinetti, M and Delogu, G and Sali, M and Di Sante, G and On Behalf Of The Gemelli-Pediatric Covid-Team, }, title = {Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children.}, journal = {Journal of clinical medicine}, volume = {11}, number = {15}, pages = {}, pmid = {35955979}, issn = {2077-0383}, support = {65925795//Pfizer (Italy)/ ; 2021.0347//Fondazione Cassa Risparmio Perugia/ ; }, abstract = {Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.}, } @article {pmid35954922, year = {2022}, author = {Estebanez-Pérez, MJ and Pastora-Bernal, JM and Martín-Valero, R}, title = {The Effectiveness of a Four-Week Digital Physiotherapy Intervention to Improve Functional Capacity and Adherence to Intervention in Patients with Long COVID-19.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {15}, pages = {}, pmid = {35954922}, issn = {1660-4601}, mesh = {*COVID-19/complications/therapy ; Humans ; Physical Therapy Modalities ; Recovery of Function ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID-19 has been defined as the condition occurring in individuals with a history of probable or confirmed SARS-CoV-2 infection, with related symptoms lasting at least 2 months and not explainable by an alternative diagnosis. The practice of digital physiotherapy presents itself as a promising complementary treatment method to standard physiotherapy, playing a key role in the recovery of function in subjects who have passed the disease and who maintain some symptomatology over time. The aims of this research are to explore the effect of a digital physiotherapy intervention on functional recovery in patients diagnosed with Long COVID-19 and to identify the level of adherence to the treatment carried out. A quasi-experimental pre-post study assessed initially and at the end of the 4-week intervention the functional capacity (1-min STS and SPPB) and the adherence (software) of a total of 32 participants. After the 4-week digital physiotherapy practice intervention with an individualised and customise exercise programme, a statistically significant improvement was observed (p < 0.05) with a small to medium effect size, high adherence rates and values above the minimal clinically important difference (MCID). We consider our intervention feasible, safe and consistent with our objectives. However, further randomised clinical trials and studies with larger samples are needed to draw extrapolable conclusions. Trial registration NCT04742946.}, } @article {pmid35954630, year = {2022}, author = {Fernández-de-Las-Peñas, C and Rodríguez-Jiménez, J and Palacios-Ceña, M and de-la-Llave-Rincón, AI and Fuensalida-Novo, S and Florencio, LL and Ambite-Quesada, S and Ortega-Santiago, R and Arias-Buría, JL and Liew, BXW and Hernández-Barrera, V and Cigarán-Méndez, M}, title = {Psychometric Properties of the Hospital Anxiety and Depression Scale (HADS) in Previously Hospitalized COVID-19 Patients.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {15}, pages = {}, pmid = {35954630}, issn = {1660-4601}, mesh = {Aged ; Anxiety/psychology ; *COVID-19/complications ; Cohort Studies ; Depression/psychology ; Female ; Hospitals ; Humans ; Male ; Middle Aged ; Psychometrics ; Reproducibility of Results ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is associated with psychological/emotional disturbances. This study aimed to assess internal consistency, reliability, and construct validity of the Hospital Anxiety and Depressive Scale (HADS), as a patient-reported outcome measure (PROM) for evaluating emotional consequences of SARS-CoV-2 in hospitalized COVID-19 survivors with long COVID. The LONG-COVID-EXP-CM is a multicenter cohort study including patients hospitalized by COVID-19 during the first wave of the pandemic in five hospitals in Madrid. A total of 1969 (age: 61 ± 16 years, 46.5% women) COVID-19 survivors experiencing post-COVID symptoms a mean of 8.4 ± 1.5 months after hospital discharge completed HADS. Internal consistency (Cronbach α), reliability (item-internal consistency, item-discriminant validity), construct validity (confirmatory factor analysis), and floor effect and ceiling effect were calculated. The mean time for fulfilling HADS was 65 ± 12 s. A ceiling effect ranging from 1.99% to 13.74% and a floor effect ranging from 43.05% to 77.77% was observed. Based on the item-scale correlation coefficients, the Cronbach's alpha values reflecting the internal consistency reliability were 0.890 for the anxiety scale (HADS-A) and 0.856 for the depressive scale (HADS-D) The correlation coefficient between HADS-A and HADS-D scores was excellent (r: 0.878). The confirmatory factor analysis revealed that five out of the seven fitness indexes were excellent: CFI = 0.969, NNFI = 0.963; TLI = 0.963; AGFI = 0.951; GFI = 0.972), supporting good construct validity. In conclusion, this study indicates that both anxiety and depressive symptoms scales of HADS had overall good psychometric properties to be used for assessing psychological and emotional stress in COVID-19 survivors with long COVID.}, } @article {pmid35953502, year = {2022}, author = {Sinclair, JE and Mayfield, HJ and Short, KR and Brown, SJ and Puranik, R and Mengersen, K and Litt, JCB and Lau, CL}, title = {A Bayesian network analysis quantifying risks versus benefits of the Pfizer COVID-19 vaccine in Australia.}, journal = {NPJ vaccines}, volume = {7}, number = {1}, pages = {93}, pmid = {35953502}, issn = {2059-0105}, support = {1193826//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 2007919//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, abstract = {The Pfizer COVID-19 vaccine is associated with increased myocarditis incidence. Constantly evolving evidence regarding incidence and case fatality of COVID-19 and myocarditis related to infection or vaccination, creates challenges for risk-benefit analysis of vaccination. Challenges are complicated further by emerging evidence of waning vaccine effectiveness, and variable effectiveness against variants. Here, we build on previous work on the COVID-19 Risk Calculator (CoRiCal) by integrating Australian and international data to inform a Bayesian network that calculates probabilities of outcomes for the delta variant under different scenarios of Pfizer COVID-19 vaccine coverage, age groups (≥12 years), sex, community transmission intensity and vaccine effectiveness. The model estimates that in a population where 5% were unvaccinated, 5% had one dose, 60% had two doses and 30% had three doses, there was a substantially greater probability of developing (239-5847 times) and dying (1430-384,684 times) from COVID-19-related than vaccine-associated myocarditis (depending on age and sex). For one million people with this vaccine coverage, where transmission intensity was equivalent to 10% chance of infection over 2 months, 68,813 symptomatic COVID-19 cases and 981 deaths would be prevented, with 42 and 16 expected cases of vaccine-associated myocarditis in males and females, respectively. These results justify vaccination in all age groups as vaccine-associated myocarditis is generally mild in the young, and there is unequivocal evidence for reduced mortality from COVID-19 in older individuals. The model may be updated to include emerging best evidence, data pertinent to different countries or vaccines and other outcomes such as long COVID.}, } @article {pmid35953265, year = {2022}, author = {Gasnier, M and Choucha, W and Radiguer, F and Faulet, T and Chappell, K and Bougarel, A and Kondarjian, C and Thorey, P and Baldacci, A and Ballerini, M and Ait Tayeb, AEK and Herrero, H and Hardy-Leger, I and Meyrignac, O and Morin, L and Lecoq, AL and Pham, T and Noel, N and Jollant, F and Montani, D and Monnet, X and Becquemont, L and Corruble, E and Colle, R and , }, title = {Comorbidity of long COVID and psychiatric disorders after a hospitalisation for COVID-19: a cross-sectional study.}, journal = {Journal of neurology, neurosurgery, and psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1136/jnnp-2021-328516}, pmid = {35953265}, issn = {1468-330X}, abstract = {OBJECTIVES: Long COVID is a major public health issue. Whether long COVID is comorbid with psychiatric disorders remains unclear. Here, we investigate the association between long COVID, psychiatric symptoms and psychiatric disorders.

DESIGN: Cross-sectional.

SETTINGS: Bicêtre Hospital, France, secondary care.

PARTICIPANTS: One hundred seventy-seven patients admitted in intensive care unit during acute phase and/or reporting long COVID complaints were assessed 4 months after hospitalisation for an acute COVID.

MAIN OUTCOME MEASURES: Eight long COVID complaints were investigated: fatigue, respiratory and cognitive complaints, muscle weakness, pain, headache, paraesthesia and anosmia. The number of complaints, the presence/absence of each COVID-19 complaint as well as lung CT scan abnormalities and objective cognitive impairment) were considered. Self-reported psychiatric symptoms were assessed with questionnaires. Experienced psychiatrists assessed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based diagnoses of psychiatric disorders.

RESULTS: One hundred and fifteen (65%) patients had at least one long COVID complaint. The number of long COVID complaints was associated with psychiatric symptoms. The number of long COVID complaints was higher in patients with psychiatric disorders (mean (m) (SD)=2.47 (1.30), p<0.05), new-onset psychiatric disorders (m (SD)=2.41 (1.32), p<0.05) and significant suicide risk (m (SD)=2.67 (1.32), p<0.05) than in patients without any psychiatric disorder (m (SD)=1.43 (1.48)). Respiratory complaints were associated with a higher risk of psychiatric disorder and new-onset psychiatric disorder, and cognitive complaints were associated with a higher risk of psychiatric disorder.

CONCLUSIONS: Long COVID is associated with psychiatric disorders, new-onset psychiatric disorders and suicide risk. Psychiatric disorders and suicide risk should be systematically assessed in patients with long COVID.}, } @article {pmid35952496, year = {2022}, author = {Ozonoff, A and Schaenman, J and Jayavelu, ND and Milliren, CE and Calfee, CS and Cairns, CB and Kraft, M and Baden, LR and Shaw, AC and Krammer, F and van Bakel, H and Esserman, DA and Liu, S and Sesma, AF and Simon, V and Hafler, DA and Montgomery, RR and Kleinstein, SH and Levy, O and Bime, C and Haddad, EK and Erle, DJ and Pulendran, B and Nadeau, KC and Davis, MM and Hough, CL and Messer, WB and Higuita, NIA and Metcalf, JP and Atkinson, MA and Brakenridge, SC and Corry, D and Kheradmand, F and Ehrlich, LIR and Melamed, E and McComsey, GA and Sekaly, R and Diray-Arce, J and Peters, B and Augustine, AD and Reed, EF and Altman, MC and Becker, PM and Rouphael, N and , }, title = {Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104208}, pmid = {35952496}, issn = {2352-3964}, support = {U19 AI090023/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; U19 AI062629/AI/NIAID NIH HHS/United States ; U19 AI077439/AI/NIAID NIH HHS/United States ; U19 AI128910/AI/NIAID NIH HHS/United States ; R01 AI104870/AI/NIAID NIH HHS/United States ; U19 AI118626/AI/NIAID NIH HHS/United States ; U19 AI167891/AI/NIAID NIH HHS/United States ; U19 AI167903/AI/NIAID NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01 AI145835/AI/NIAID NIH HHS/United States ; U19 AI128913/AI/NIAID NIH HHS/United States ; R01 AI132774/AI/NIAID NIH HHS/United States ; U19 AI118608/AI/NIAID NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; U54 AI142766/AI/NIAID NIH HHS/United States ; U19 AI057266/AI/NIAID NIH HHS/United States ; K08 AA027837/AA/NIAAA NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; K08 HL141623/HL/NHLBI NIH HHS/United States ; P01 AI153559/AI/NIAID NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; R01 AI135803/AI/NIAID NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Creatinine ; Female ; Hospitalization ; Humans ; Male ; Phenotype ; Prospective Studies ; RNA, Viral ; SARS-CoV-2 ; Severity of Illness Index ; Troponin ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.

METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.

FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.

INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.

FUNDING: NIH.}, } @article {pmid35951647, year = {2022}, author = {Crunfli, F and Carregari, VC and Veras, FP and Silva, LS and Nogueira, MH and Antunes, ASLM and Vendramini, PH and Valença, AGF and Brandão-Teles, C and Zuccoli, GDS and Reis-de-Oliveira, G and Silva-Costa, LC and Saia-Cereda, VM and Smith, BJ and Codo, AC and de Souza, GF and Muraro, SP and Parise, PL and Toledo-Teixeira, DA and Santos de Castro, ÍM and Melo, BM and Almeida, GM and Firmino, EMS and Paiva, IM and Silva, BMS and Guimarães, RM and Mendes, ND and Ludwig, RL and Ruiz, GP and Knittel, TL and Davanzo, GG and Gerhardt, JA and Rodrigues, PB and Forato, J and Amorim, MR and Brunetti, NS and Martini, MC and Benatti, MN and Batah, SS and Siyuan, L and João, RB and Aventurato, ÍK and Rabelo de Brito, M and Mendes, MJ and da Costa, BA and Alvim, MKM and da Silva Júnior, JR and Damião, LL and de Sousa, IMP and da Rocha, ED and Gonçalves, SM and Lopes da Silva, LH and Bettini, V and Campos, BM and Ludwig, G and Tavares, LA and Pontelli, MC and Viana, RMM and Martins, RB and Vieira, AS and Alves-Filho, JC and Arruda, E and Podolsky-Gondim, GG and Santos, MV and Neder, L and Damasio, A and Rehen, S and Vinolo, MAR and Munhoz, CD and Louzada-Junior, P and Oliveira, RD and Cunha, FQ and Nakaya, HI and Mauad, T and Duarte-Neto, AN and Ferraz da Silva, LF and Dolhnikoff, M and Saldiva, PHN and Farias, AS and Cendes, F and Moraes-Vieira, PMM and Fabro, AT and Sebollela, A and Proença-Modena, JL and Yasuda, CL and Mori, MA and Cunha, TM and Martins-de-Souza, D}, title = {Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, number = {35}, pages = {e2200960119}, pmid = {35951647}, issn = {1091-6490}, mesh = {Astrocytes/pathology/virology ; *Brain/pathology/virology ; *COVID-19/complications/pathology ; *Central Nervous System Viral Diseases/etiology/pathology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.}, } @article {pmid35951203, year = {2023}, author = {Osiaevi, I and Schulze, A and Evers, G and Harmening, K and Vink, H and Kümpers, P and Mohr, M and Rovas, A}, title = {Persistent capillary rarefication in long COVID syndrome.}, journal = {Angiogenesis}, volume = {26}, number = {1}, pages = {53-61}, pmid = {35951203}, issn = {1573-7209}, mesh = {Humans ; *Capillaries ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; Critical Illness ; *COVID-19/metabolism ; SARS-CoV-2 ; Glycocalyx ; Microcirculation ; }, abstract = {BACKGROUND: Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after the initial infection.

METHODS: This prospective, observational study included 58 participants, 27 of whom were long COVID patients with persistent symptoms > 12 weeks after recovery from PCR-confirmed SARS-CoV-2 infection. Fifteen healthy volunteers and a historical cohort of critically ill COVID-19 patients (n = 16) served as controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version of Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell velocity (VRBC) and the microvascular health score (MVHS™) in sublingual microvessels with diameters 4-25 µm.

MEASUREMENTS AND MAIN RESULTS: Although dimensions of the glycocalyx were comparable to those of healthy controls, a µm-precise analysis showed a significant decrease of vascular density, that exclusively affected very small capillaries (D5: - 45.16%; D6: - 35.60%; D7: - 22.79%). Plotting VRBC of capillaries and feed vessels showed that the number of capillaries perfused in long COVID patients was comparable to that of critically ill COVID-19 patients and did not respond adequately to local variations of tissue metabolic demand. MVHS was markedly reduced in the long COVID cohort (healthy 3.87 vs. long COVID 2.72 points; p = 0.002).

CONCLUSIONS: Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.}, } @article {pmid35950630, year = {2023}, author = {Rohrhofer, J and Graninger, M and Lettenmaier, L and Schweighardt, J and Gentile, SA and Koidl, L and Ret, D and Stingl, M and Puchhammer-Stöckl, E and Untersmayr, E}, title = {Association between Epstein-Barr-Virus reactivation and development of Long-COVID fatigue.}, journal = {Allergy}, volume = {78}, number = {1}, pages = {297-299}, pmid = {35950630}, issn = {1398-9995}, mesh = {Humans ; *Post-Acute COVID-19 Syndrome ; *COVID-19 ; Antibodies, Viral ; Immunoglobulin G ; Fatigue ; Virus Activation ; }, } @article {pmid35949299, year = {2022}, author = {Bogdanov, VY and Khirmanov, VN}, title = {SARS-CoV-2, platelets, and endothelium: coexistence in space and time, or a pernicious ménage à trois?.}, journal = {Vascular biology (Bristol, England)}, volume = {4}, number = {1}, pages = {R35-R43}, pmid = {35949299}, issn = {2516-5658}, abstract = {As we enter year 3 of SARS-CoV-2 pandemic, long-term consequences of COVID-19 have become a major public health issue worldwide; however, the molecular and cellular underpinnings of 'long COVID' remain very poorly understood. A paradigm has recently emerged that thrombo-inflammatory consequences of SARS-CoV-2's impact on endothelial cells and platelets likely play a significant role in the development of chronic symptomatology associated with COVID-19. In this brief overview, we discuss the recent findings pertaining to the detection of SARS-CoV-2 virions in vascular cell subtypes, the contribution of the coagulation system to the development of 'long COVID', and the potential role of stem/progenitor cells in the viral and thrombotic dissemination in this disorder.}, } @article {pmid35945375, year = {2022}, author = {Ledford, H}, title = {Long-COVID treatments: why the world is still waiting.}, journal = {Nature}, volume = {608}, number = {7922}, pages = {258-260}, pmid = {35945375}, issn = {1476-4687}, mesh = {*Antiviral Agents/therapeutic use ; *COVID-19/complications/virology ; Humans ; SARS-CoV-2/pathogenicity ; Time Factors ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, } @article {pmid35942159, year = {2022}, author = {Ilieva, M and Tschaikowski, M and Vandin, A and Uchida, S}, title = {The current status of gene expression profilings in COVID-19 patients.}, journal = {Clinical and translational discovery}, volume = {2}, number = {3}, pages = {e104}, pmid = {35942159}, issn = {2768-0622}, abstract = {BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept through every part of the world. Because of its impact, international efforts have been underway to identify the variants of SARS-CoV-2 by genome sequencing and to understand the gene expression changes in COVID-19 patients compared to healthy donors using RNA sequencing (RNA-seq) assay. Within the last two and half years since the emergence of SARS-CoV-2, a large number of OMICS data of COVID-19 patients have accumulated. Yet, we are still far from understanding the disease mechanism. Further, many people suffer from long-term effects of COVID-19; calling for a more systematic way to data mine the generated OMICS data, especially RNA-seq data.

METHODS: By searching gene expression omnibus (GEO) using the key terms, COVID-19 and RNA-seq, 108 GEO entries were identified. Each of these studies was manually examined to categorize the studies into bulk or single-cell RNA-seq (scRNA-seq) followed by an inspection of their original articles.

RESULTS: The currently available RNA-seq data were generated from various types of patients' samples, and COVID-19 related sample materials have been sequenced at the level of RNA, including whole blood, different components of blood [e.g., plasma, peripheral blood mononuclear cells (PBMCs), leukocytes, lymphocytes, monocytes, T cells], nasal swabs, and autopsy samples (e.g., lung, heart, liver, kidney). Of these, RNA-seq studies using whole blood, PBMCs, nasal swabs and autopsy/biopsy samples were reviewed to highlight the major findings from RNA-seq data analysis.

CONCLUSIONS: Based on the bulk and scRNA-seq data analysis, severe COVID-19 patients display shifts in cell populations, especially those of leukocytes and monocytes, possibly leading to cytokine storms and immune silence. These RNA-seq data form the foundation for further gene expression analysis using samples from individuals suffering from long COVID.}, } @article {pmid35942002, year = {2022}, author = {Athavale, T and Athavale, A and Bairy, A and Jansari, M and Karpe, S and Nagare, M and Mutkule, V}, title = {Hemoptysis after COVID: Pulmonary artery pseudoaneurysm treated with endovascular coiling.}, journal = {Respiratory medicine case reports}, volume = {39}, number = {}, pages = {101708}, pmid = {35942002}, issn = {2213-0071}, abstract = {Pulmonary artery pseudoaneurysms are a rare but life-threatening cause of hemoptysis. These are saccular dilatations of the pulmonary artery which do not involve all the three layers of the vessel and are prone to rupture. PAPAs are most commonly associated with infections but may also be caused by vasculitis, lung fibrosis, pulmonary hypertension and a multitude of other causes. CT pulmonary angiography is the diagnostic modality of choice allowing delineation of the PAPA, underlying cause and allowing planning of further management. Although treating the underlying cause is an important part of management, endovascular intervention is required in cases with hemoptysis. Long COVID is an entity that is still under evaluation. It has multisystem involvement. We describe the case of a 30-year-old teacher with hemoptysis after COVID who was diagnosed with a PAPA of segmental branch of left upper lobar pulmonary artery and treated with endovascular embolization with coils and glue. His hemoptysis has stopped since then. He also had pulmonary fibrosis and growth of multidrug resistant Klebsiella pneumoniae in sputum. These were treated medically and he has resumed his work as a teacher.}, } @article {pmid35940086, year = {2022}, author = {Desai, SS and Nguyen, AL and Bernstein, GA}, title = {Letter to editor: Case report of long COVID-19 with psychosis in a child.}, journal = {Psychiatry research}, volume = {316}, number = {}, pages = {114743}, pmid = {35940086}, issn = {1872-7123}, mesh = {*COVID-19/complications ; Child ; Humans ; *Psychotic Disorders/complications ; *Severe acute respiratory syndrome-related coronavirus ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35938771, year = {2022}, author = {Arun, S and Storan, A and Myers, B}, title = {Mast cell activation syndrome and the link with long COVID.}, journal = {British journal of hospital medicine (London, England : 2005)}, volume = {83}, number = {7}, pages = {1-10}, doi = {10.12968/hmed.2022.0123}, pmid = {35938771}, issn = {1750-8460}, mesh = {*COVID-19/complications ; Histamine/metabolism ; Humans ; *Mast Cell Activation Syndrome ; Mast Cells/metabolism ; Neoplasm Recurrence, Local ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Mast cells are innate immune cells found in connective tissues throughout the body, most prevalent at tissue-environment interfaces. They possess multiple cell-surface receptors which react to various stimuli and, after activation, release many mediators including histamine, heparin, cytokines, prostaglandins, leukotrienes and proteases. In mast cell activation syndrome, excessive amounts of inflammatory mediators are released in response to triggers such as foods, fragrances, stress, exercise, medications or temperature changes. Diagnostic markers may be difficult to assess because of their rapid degradation; these include urinary N-methyl histamine, urinary prostaglandins D2, DM and F2α and serum tryptase (which is stable) in the UK. Self-management techniques, medications and avoiding triggers may improve quality of life. Treatments include mast cell mediator blockers, mast cell stabilisers and anti-inflammatory agents. 'Long COVID' describes post-COVID-19 syndrome when symptoms persist for more than 12 weeks after initial infection with no alternative diagnosis. Both mast cell activation syndrome and long COVID cause multiple symptoms. It is theorised that COVID-19 infection could lead to exaggeration of existing undiagnosed mast cell activation syndrome, or could activate normal mast cells owing to the persistence of viral particles. Other similarities include the relapse-remission cycle and improvements with similar treatments. Importantly, however, aside from mast cell disorders, long COVID could potentially be attributed to several other conditions.}, } @article {pmid35938281, year = {2022}, author = {Wickert, K and Romeo, JM and Rumrill, P and Sheppard-Jones, K and McCurry, S}, title = {Return to work considerations in the lingering COVID-19 Era: Long COVID, multiple chemical sensitivity, and universal design.}, journal = {Work (Reading, Mass.)}, volume = {73}, number = {2}, pages = {355-360}, doi = {10.3233/WOR-223641}, pmid = {35938281}, issn = {1875-9270}, mesh = {Humans ; *COVID-19 ; Return to Work ; Universal Design ; *Multiple Chemical Sensitivity ; Workplace ; Post-Acute COVID-19 Syndrome ; }, abstract = {This article discusses how COVID-19 has impacted the American workforce, symptoms of Long COVID syndrome, Multiple Chemical Sensitivity, and ways to avoid triggering its symptoms when sanitizing the workplace and using Universal Design practices to increase accessibility and decrease transmission of COVID-19 among workers. Interface with healthcare providers, rehabilitation professionals, and employers is emphasized.}, } @article {pmid35938280, year = {2022}, author = {Gualano, MR and Rossi, MF and Borrelli, I and Santoro, PE and Amantea, C and Daniele, A and Tumminello, A and Moscato, U}, title = {Returning to work and the impact of post COVID-19 condition: A systematic review.}, journal = {Work (Reading, Mass.)}, volume = {73}, number = {2}, pages = {405-413}, doi = {10.3233/WOR-220103}, pmid = {35938280}, issn = {1875-9270}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Quality of Life ; World Health Organization ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic is still ongoing, with rapidly increasing cases all over the world, and the emerging issue of post COVID-19 (or Long COVID-19) condition is impacting the occupational world.

OBJECTIVE: The aim of this systematic review was to evaluate the impact of lasting COVID-19 symptoms or disability on the working population upon their return to employment.

METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements we performed a systematic review in December 2021, screening three databases (PubMed, ISI Web of Knowledge, Scopus), for articles investigating return to work in patients that were previously hospitalized due to COVID-19. A hand-searched was then performed through the references of the included systematic review. A quality assessment was performed on the included studies.

RESULTS: Out of the 263 articles found through the initial search, 11 studies were included in this systematic review. The selected studies were divided based on follow-up time, in two months follow-up, follow-up between two and six months, and six months follow-up. All the studies highlighted an important impact of post COVID-19 condition in returning to work after being hospitalized, with differences based on follow-up time, home Country and mean/median age of the sample considered.

CONCLUSIONS: This review highlighted post COVID-19 condition as a rising problem in occupational medicine, with consequences on workers' quality of life and productivity. The role of occupational physicians could be essential in applying limitations to work duties or hours and facilitating the return to employment in workers with a post COVID-19 condition.}, } @article {pmid35937924, year = {2022}, author = {Groopman, DS and Elkiss, M}, title = {Energetic Medicine and Long COVID.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {154-156}, pmid = {35937924}, issn = {1933-6586}, } @article {pmid35934258, year = {2022}, author = {Solomon, M and Liang, C}, title = {Human coronaviruses: The emergence of SARS-CoV-2 and management of COVID-19.}, journal = {Virus research}, volume = {319}, number = {}, pages = {198882}, pmid = {35934258}, issn = {1872-7492}, support = {//CIHR/Canada ; }, mesh = {Betacoronavirus/genetics ; *Coronavirus Infections/drug therapy ; Humans ; *Pneumonia, Viral/prevention & control ; SARS-CoV-2/genetics ; *COVID-19 Drug Treatment ; }, abstract = {To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.}, } @article {pmid35933996, year = {2022}, author = {Brightling, CE and Evans, RA}, title = {Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?.}, journal = {Lancet (London, England)}, volume = {400}, number = {10350}, pages = {411-413}, pmid = {35933996}, issn = {1474-547X}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35933347, year = {2022}, author = {Pretorius, E and Venter, C and Laubscher, GJ and Kotze, MJ and Oladejo, SO and Watson, LR and Rajaratnam, K and Watson, BW and Kell, DB}, title = {Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC).}, journal = {Cardiovascular diabetology}, volume = {21}, number = {1}, pages = {148}, pmid = {35933347}, issn = {1475-2840}, mesh = {Amyloid ; *COVID-19/complications/epidemiology ; *Diabetes Mellitus, Type 2 ; Female ; Fibrin ; Humans ; Male ; Prevalence ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of Long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities.

METHODS: In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases.

RESULTS: Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.

CONCLUSIONS: Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of Long COVID/PASC as a major determinant of effective treatment, including those focusing on reducing clot burden and platelet hyperactivation.}, } @article {pmid35930487, year = {2022}, author = {Warren, S and Drake, J and Wu, CK}, title = {Cognitive Complications of COVID-19 Infection.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {27-30}, pmid = {35930487}, issn = {2327-2228}, mesh = {*COVID-19/complications ; Cognition ; Executive Function/physiology ; Humans ; Neuropsychological Tests ; SARS-CoV-2 ; }, abstract = {SARS-CoV-2 is associated with a post-infectious neurocognitive syndrome characterized by fatigue and deficits in attention, memory, and executive function. As screening cognitive testing generally remains normal, the pathophysiologic basis of these symptoms remains controversial and there is no standardized treatment paradigm. We present a clinical case demonstrative of typical neurocognitive sequelae of SARS-CoV-2 infection, highlighting medical and social factors that may have contributed to the severity of symptoms. We discuss the pathophysiologic evidence for cognitive "brain fog" following COVID-19 infection as well as lifestyle changes and rehabilitation strategies that may improve recovery. As the benefits of pharmacologic therapy remain unproven, we close with a brief discussion of medication options that might be appropriate targets for future clinical trials in the context of rehabilitative treatment.}, } @article {pmid35930486, year = {2022}, author = {Stiles, KA and Weisbach, E and Cahill, JF}, title = {Neurological Sequelae of COVID-19 in Rehabilitation Settings.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {23-26}, pmid = {35930486}, issn = {2327-2228}, mesh = {*COVID-19/complications ; *Guillain-Barre Syndrome/complications ; Headache ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurological symptoms of post-acute sequelae of COVID-19 (PASC), also known as Long COVID, are recognized. Four neurological syndromes (transverse myelitis, ischemic stroke, headache, and Guillain-Barré syndrome) associated with PASC are reviewed here, with a particular focus on issues related to rehabilitation.}, } @article {pmid35930485, year = {2022}, author = {Khetpal, V and Berkowitz, J and Vijayakumar, S and Choudhary, G and Mukand, JA and Rudolph, JL and Wu, WC and Erqou, S}, title = {Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {16-22}, pmid = {35930485}, issn = {2327-2228}, mesh = {Arrhythmias, Cardiac/diagnosis/etiology/therapy ; *COVID-19/complications ; COVID-19 Testing ; Chest Pain/etiology ; Humans ; *Myocarditis ; Post-Acute COVID-19 Syndrome ; }, abstract = {Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.}, } @article {pmid35930484, year = {2022}, author = {Simon, M and Simmons, JE}, title = {A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {11-15}, pmid = {35930484}, issn = {2327-2228}, mesh = {*COVID-19/complications ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {With the SARS-CoV-2 pandemic continuing into its third year, the number of patients who survive acute COVID-19 infection but go on to develop long-term symptoms is increasing daily. Those individuals who experience one or more of a variety of persistent symptoms post-COVID-19 are now diagnosed with the syndrome called post-acute sequelae of COVID-19 (PASC), often colloquially called "Long COVID." This article discusses relevant research and current hypotheses regarding the pathophysiology and management of respiratory symptoms of PASC, in order to provide primary care physicians with context for management of this heterogeneous population. We focus on the growing body of research that supports the use of pulmonary rehabilitation for patients with PASC to improve symptoms and quality of life.}, } @article {pmid35930483, year = {2022}, author = {Mukand, JA}, title = {RIMJ Special Section: The Evaluation & Rehabilitation of Long COVID.}, journal = {Rhode Island medical journal (2013)}, volume = {105}, number = {7}, pages = {7-10}, pmid = {35930483}, issn = {2327-2228}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35930181, year = {2022}, author = {Cristillo, V and Pilotto, A and Piccinelli, SC and Gipponi, S and Leonardi, M and Bezzi, M and Padovani, A}, title = {Predictors of "brain fog" 1 year after COVID-19 disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {10}, pages = {5795-5797}, pmid = {35930181}, issn = {1590-3478}, mesh = {Brain ; *COVID-19/complications ; Fatigue/epidemiology/etiology ; Humans ; Mental Status and Dementia Tests ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Brain fog has been described up to 1 year after SARS-CoV-2 infection, notwithstanding the underlying mechanisms are still poorly investigated. In this study, we aimed to evaluate the prevalence of cognitive complaints at 1-year follow-up and to identify the factors related to persistent brain fog in COVID-19 patients.

METHODS: Out of 246 COVID patients, hospitalized from March 1st to May 31st, a sample of 137 patients accepted to be evaluated at 1 year from discharge, through a full clinical, neurological, and psychological examination, including the Montreal Cognitive Assessment (MoCA), impact of event scale-revised (IES-R), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), and fatigue severity scale (FSS). Subjects with prior cognitive impairment and/or psychiatric disorders were excluded.

RESULTS: Patients with cognitive disorders exhibited lower MoCA score (22.9 ± 4.3 vs. 26.3 ± 3.1, p = 0.002) and higher IES-R score (33.7 ± 18.5 vs. 26.4 ± 16.3, p = 0.050), SDS score (40.9 ± 6.5 vs. 35.5 ± 8.6, p = 0.004), and fatigue severity scale score (33.6 ± 16.1 vs. 23.7 ± 12.5, p = 0.001), compared to patients without cognitive complaints. Logistic regression showed a significant correlation between brain fog and the self-rating depression scale values (p = 0.020), adjusted for age (p = 0.445), sex (p = 0.178), premorbid Cumulative Illness Rating Scale (CIRS) (p = 0.288), COVID-19 severity (BCRSS) (p = 0.964), education level (p = 0.784) and MoCA score (p = 0.909).

CONCLUSIONS: Our study showed depression as the strongest predictor of persistent brain fog, adjusting for demographic and clinical variables. Wider longitudinal studies are warranted to better explain cognitive difficulties after COVID-19.}, } @article {pmid35926861, year = {2022}, author = {Mahase, E}, title = {Covid-19: One in eight adults develops long covid symptoms, study suggests.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o1946}, doi = {10.1136/bmj.o1946}, pmid = {35926861}, issn = {1756-1833}, mesh = {Adult ; *COVID-19/complications ; Depression/diagnosis ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35925863, year = {2022}, author = {Xie, Y and Butler, M}, title = {Serum N-glycomic profiling may provide potential signatures for surveillance of COVID-19.}, journal = {Glycobiology}, volume = {32}, number = {10}, pages = {871-885}, pmid = {35925863}, issn = {1460-2423}, mesh = {*COVID-19/diagnosis ; *Glycomics ; Glycoproteins/chemistry ; Humans ; Polysaccharides/chemistry ; SARS-CoV-2 ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Disease development and progression are often associated with aberrant glycosylation, indicating that changes in biological fluid glycome may potentially serve as disease signatures. The corona virus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a significant threat to global human health. However, the effect of SARS-CoV-2 infection on the overall serum N-glycomic profile has been largely unexplored. Here, we extended our 96-well-plate-based high-throughput, high-sensitivity N-glycan profiling platform further with the aim of elucidating potential COVID-19-associated serum N-glycomic alterations. Use of this platform revealed both similarities and differences between the serum N-glycomic fingerprints of COVID-19 positive and control cohorts. Although there were no specific glycan peaks exclusively present or absent in COVID-19 positive cohort, this cohort showed significantly higher levels of glycans and variability. On the contrary, the overall N-glycomic profiles for healthy controls were well-contained within a narrow range. From the serum glycomic analysis, we were able to deduce changes in different glycan subclasses sharing certain structural features. Of significance was the hyperbranched and hypersialylated glycans and their derived glycan subclass traits. T-distributed stochastic neighbor embedding and hierarchical heatmap clustering analysis were performed to identify 13 serum glycomic variables that potentially distinguished the COVID-19 positive from healthy controls. Such serum N-glycomic changes described herein may indicate or correlate to the changes in serum glycoproteins upon COVID-19 infection. Furthermore, mapping the serum N-glycome following SARS-CoV-2 infection may help us better understand the disease and enable "Long-COVID" surveillance to capture the full spectrum of persistent symptoms.}, } @article {pmid35925075, year = {2022}, author = {Herold, S and Salzberger, B}, title = {[Long COVID-a new challenge].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {811-812}, pmid = {35925075}, issn = {2731-7099}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35925074, year = {2022}, author = {Renz-Polster, H and Scheibenbogen, C}, title = {[Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {830-839}, pmid = {35925074}, issn = {2731-7099}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis ; Humans ; Pain ; }, abstract = {BACKGROUND: A sizable part of post-COVID syndrome meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A doubling of cases of ME/CFS within the next years is therefore projected.

OBJECTIVES: Presentation of the current state of knowledge on ME/CFS.

MATERIALS AND METHODS: Unsystematic review of the literature and of own contributions in research and patient care.

RESULTS AND CONCLUSIONS: ME/CFS is a neuroimmunological disease, mostly infection-induced, usually persisting throughout life. Clinically it is characterized by fatigue lasting at least 6 months and the defining core feature of exercise intolerance (post-exertional malaise, PEM). Exercise intolerance is defined as a worsening of symptoms after (even mild) everyday exertion, which usually begins after several hours or on the following day, is still noticeable at least 14 h after exertion, and often lasts for several days (up to weeks or longer). Furthermore, ME/CFS is characterized by pain, disturbances of sleep, thinking and memory, and dysregulation of the circulatory, endocrine, and immune systems. As a separate clinical entity, ME/CFS should be distinguished from chronic fatigue, which occurs as a symptom of a range of very different diseases. The diagnosis of ME/CFS is made clinically using established international diagnostic criteria and requires careful stepwise diagnosis to exclude other diagnoses. A causal therapy for ME/CFS has not been established; the focus is on symptoms relief, treatment of the often accompanying orthostatic intolerance, and assistance with anticipatory energy management (pacing).}, } @article {pmid35925073, year = {2022}, author = {Sommer, N and Schmeck, B}, title = {[Pulmonary manifestations in long COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {819-829}, pmid = {35925073}, issn = {2731-7099}, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; *Lung Diseases, Interstitial/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Pulmonary manifestations are very common sequelae after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections, which are summarized under the term long COVID (coronavirus disease) syndrome.

AIM/METHODS: This article summarizes the current literature on pulmonary manifestations with a focus on expert opinions and recommendations.

RESULTS: After chronic fatigue, dyspnea is the most common symptom in patients with long COVID syndrome. Pathological findings are mainly found after a severe acute course of COVID-19 and include radiological changes with characteristics of interstitial lung diseases, restrictive ventilation patterns and limitations in diffusion capacity as the most common pathological finding. Although both symptoms and pathological pulmonary alterations improve over time, some patients may still suffer from abnormalities months after the acute infection. The relevance of the pathological findings, as well as the involvement of functional respiratory limitations, cardiopulmonary deconditioning, non-somatic causes and pre-existing lung diseases, is currently unclear. The advanced diagnostic assessment thus focusses on high-risk patients and includes, in addition to imaging and pulmonary function tests, a cardiopulmonary exercise test and, if the findings are unclear, an echocardiography to diagnose a pulmonary vascular component. The therapeutic options currently include treatment of the underlying causes of the symptoms (e.g. interstitial lung diseases, cough) according to the respective guidelines and rehabilitation measures.

DISCUSSION: The current knowledge about pulmonary manifestations in long COVID patients is constantly being expanded, but due to limited availability of clinical trials, there are still no evidence-based guidelines for the diagnosis and therapy of pulmonary manifestations in long COVID syndrome.}, } @article {pmid35925072, year = {2022}, author = {Bauernfeind, S and Schmidt, B}, title = {[The value of COVID-19 vaccination in the context of Long-COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {840-850}, pmid = {35925072}, issn = {2731-7099}, mesh = {*COVID-19/complications/prevention & control ; COVID-19 Vaccines/therapeutic use ; Humans ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {There are currently no strategies available on how to deal with Long-COVID (COVID "coronavirus disease"). COVID-19 vaccination could be both a preemptive and a therapeutic option for the future. The evaluation of the available studies is complicated by varying definitions. There are, however, indications that (complete) COVID-19 vaccination is able not only to prevent symptomatic infection but also to reduce the risk of Long-COVID. In some patients with Long-COVID, symptoms are modified after (first and/or second) COVID-19 vaccination; however, there is no clear evidence for a real therapeutic effect on Long-COVID.}, } @article {pmid35925071, year = {2022}, author = {Pink, I and Welte, T}, title = {[Frequency, spectrum and risk factors of long COVID].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {8}, pages = {813-818}, pmid = {35925071}, issn = {2731-7099}, mesh = {*Ageusia ; *COVID-19/complications/epidemiology ; Humans ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Between 10 and 20% of individuals infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) suffer from symptoms up to weeks after initial infection. The most frequently reported symptoms include fatigue, dyspnea, anosmia and ageusia, as well as headaches, joint pain, cough, cognitive impairment and impaired sleeping. After exclusion of other etiologies and symptom duration of more than 4 weeks after initial infection this is referred to as long COVID. In contrast to acute coronavirus disease 2019 (COVID-19), no specific risk factors have been identified as yet as being associated with the occurrence of this disease. Furthermore, there are varying hypotheses concerning the pathomechanism of long COVID. Dividing patients into groups is beneficial in the clinical context. Regardless of long COVID symptoms the risk of cardiovascular events is increased even 1 year after COVID-19.}, } @article {pmid35923692, year = {2022}, author = {Luo, YS and Luo, L and Li, W and Chen, Y and Wu, GF and Chen, F and Shen, HY and Li, HM and Guo, MY and Yin, S and Zhang, K and Cheng, ZS}, title = {Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {931562}, pmid = {35923692}, issn = {1664-8021}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.}, } @article {pmid35919910, year = {2022}, author = {Ohira, M and Sano, T and Takao, M}, title = {Clinical features of patients who visited the outpatient clinic for long COVID in Japan.}, journal = {eNeurologicalSci}, volume = {28}, number = {}, pages = {100418}, pmid = {35919910}, issn = {2405-6502}, abstract = {BACKGROUND: The clinical course, comorbidity, and management of symptoms after the acute phase of coronavirus disease 2019 (COVID-19) remain controversial.

METHODS: This was a descriptive case series study, examining the characteristics of patients with longstanding symptoms related to COVID-19 who visited our outpatient clinic between 1 June and 31 December 2021. We analyzed patients' background, chief complaints, clinical course after COVID-19 onset, and clinical examination results.

RESULTS: A total of 90 patients with a mean age of 39.8 years were confirmed as having long COVID. The median time between diagnosis of COVID-19 and visiting our clinic was 66.8 days, and 89 patients (98.9%) were unvaccinated. Depression was the most common comorbidity (nine patients, 10.0%). The most common chief complaint was disturbance of smell and/or taste (35, 38.9%), followed by memory disturbance (22, 24.4%) and fatigue (29, 31.1%). Head MRI was performed for 42 (46.7%) patients, and the most common finding was sinusitis (four patients). Olfactory testing was conducted in 25 patients (27.8%) using a T&T olfactometer, and 14 patients (56%) had mild olfactory impairment. Of the five odors in the T&T, recognition of β-phenylethyl alcohol was most impaired.

CONCLUSIONS: This study describes the basic characteristics of long COVID in Japan. It suggests that long COVID is complex because it results in a wide range of symptoms.}, } @article {pmid35918096, year = {2022}, author = {Greenhalgh, T and Kane, B and Reicher, S}, title = {"Downgrade your mask before entering"-a dangerous NHS policy at a critical public health juncture.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o1929}, doi = {10.1136/bmj.o1929}, pmid = {35918096}, issn = {1756-1833}, mesh = {Health Policy ; Humans ; Masks ; Policy ; *Public Health ; *State Medicine ; }, } @article {pmid35915884, year = {2022}, author = {Platz, T and Dewey, S and Köllner, V and Schlitt, A}, title = {[Rehabilitation with coronavirus disease with SARS-CoV-2 (COVID-19)].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {147}, number = {15}, pages = {981-989}, doi = {10.1055/a-1646-5801}, pmid = {35915884}, issn = {1439-4413}, mesh = {*COVID-19/complications ; Humans ; *Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The Coronavirus disease with SARS-CoV-2 viral infection (COVID-19) and its diverse courses of disease from mild to critical illness frequently is not only an acute disease, but will - in a proportion of those affected - lead to organ structure and body function deficits that still exist or become apparent after the acute stage of disease. When clinically relevant symptoms or functional deficits (impairments) are documented more than four weeks after COVID-19 onset, the syndrome is called "Long-COVID", from 12 weeks after onset onwards "Post-COVID".In such cases and when everyday life functioning or return to work are affected by persisting deficits specialized rehabilitation treatment is indicated. An individual medical, frequently multi-professional diagnostic evaluation is mandatory in that situation: For adequate treatment, it is important to identify and objectify the individually underlying health conditions based on knowledge about the diverse potential consequences of COVID-19, to assess type and severity of functional consequences (impairments, activity limitations, and restrictions of participation) of Long-/Post-COVID individually, and then to decide on the treatment necessities and plans. With regard to rehabilitation, need and decision for either pulmonary, neurological, cardiac, or psychosomatic rehabilitation depends on the individual medical presentation.}, } @article {pmid35915417, year = {2022}, author = {Tana, C and Bentivegna, E and Cho, SJ and Harriott, AM and García-Azorín, D and Labastida-Ramirez, A and Ornello, R and Raffaelli, B and Beltrán, ER and Ruscheweyh, R and Martelletti, P}, title = {Long COVID headache.}, journal = {The journal of headache and pain}, volume = {23}, number = {1}, pages = {93}, pmid = {35915417}, issn = {1129-2377}, mesh = {*COVID-19/complications ; Headache/diagnosis/etiology/therapy ; Humans ; *Migraine Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.}, } @article {pmid35914783, year = {2022}, author = {Hereth, B and Tubig, P and Sorrels, A and Muldoon, A and Hills, K and Evans, NG}, title = {Long covid and disability: a brave new world.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {e069868}, doi = {10.1136/bmj-2021-069868}, pmid = {35914783}, issn = {1756-1833}, mesh = {*COVID-19/complications ; *Disabled Persons ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35914765, year = {2023}, author = {Nalbandian, A and Desai, AD and Wan, EY}, title = {Post-COVID-19 Condition.}, journal = {Annual review of medicine}, volume = {74}, number = {}, pages = {55-64}, doi = {10.1146/annurev-med-043021-030635}, pmid = {35914765}, issn = {1545-326X}, support = {T32 HL007854/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; *COVID-19 ; Quality of Life ; SARS-CoV-2 ; *Cognitive Dysfunction/epidemiology/etiology ; Dyspnea ; }, abstract = {An estimated 10-15% of those infected with SARS-CoV-2 may have post-COVID-19 condition. Common lingering signs and symptoms include shortness of breath, fatigue, high heart rate, and memory and cognitive dysfunction even several months after infection, often impacting survivors' quality of life. The prevalence and duration of individual symptoms remain difficult to ascertain due to the lack of standardized research methods across various studies and limited patient follow-up in clinical studies. Nonetheless, data indicate post-COVID-19 condition may occur independent of acuity of initial infection, hospitalization status, age, or pre-existing comorbidities. Risk factors may include female sex and underlying respiratory or psychiatric disease. Supportive therapies to mitigate symptoms remain the mainstay of treatment. Reassuringly, most patients experience a reduction in symptoms by 1 year. The use of a universal case definition and shared research methods will allow for further clarity regarding the pervasiveness of this entity and its long-term health consequences.}, } @article {pmid35914265, year = {2022}, author = {Montori, VM}, title = {Patients surviving COVID-19 had increased risk for incident diabetes vs. persons without COVID-19.}, journal = {Annals of internal medicine}, volume = {175}, number = {8}, pages = {JC93}, doi = {10.7326/J22-0052}, pmid = {35914265}, issn = {1539-3704}, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; *Diabetes Mellitus/epidemiology ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022;10:311-21. 35325624.}, } @article {pmid35912863, year = {2022}, author = {Ahamed, J and Laurence, J}, title = {Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches.}, journal = {The Journal of clinical investigation}, volume = {132}, number = {15}, pages = {}, pmid = {35912863}, issn = {1558-8238}, support = {R01 HL148123/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications/therapy ; Female ; Humans ; Inflammation ; SARS-CoV-2 ; *Thrombosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2-infected individuals may suffer a multi-organ system disorder known as "long COVID" or post-acute sequelae of SARS-CoV-2 infection (PASC). There are no standard treatments, the pathophysiology is unknown, and incidence varies by clinical phenotype. Acute COVID-19 correlates with biomarkers of systemic inflammation, hypercoagulability, and comorbidities that are less prominent in PASC. Macrovessel thrombosis, a hallmark of acute COVID-19, is less frequent in PASC. Female sex at birth is associated with reduced risk for acute COVID-19 progression, but with increased risk of PASC. Persistent microvascular endotheliopathy associated with cryptic SARS-CoV-2 tissue reservoirs has been implicated in PASC pathology. Autoantibodies, localized inflammation, and reactivation of latent pathogens may also be involved, potentially leading to microvascular thrombosis, as documented in multiple PASC tissues. Diagnostic assays illuminating possible therapeutic targets are discussed.}, } @article {pmid35912735, year = {2022}, author = {Koutsiaris, AG and Riri, K and Boutlas, S and Panagiotou, TN and Kotoula, M and Daniil, Z and Tsironi, EE}, title = {COVID-19 hemodynamic and thrombotic effect on the eye microcirculation after hospitalization: A quantitative case-control study.}, journal = {Clinical hemorheology and microcirculation}, volume = {82}, number = {4}, pages = {379-390}, doi = {10.3233/CH-221554}, pmid = {35912735}, issn = {1875-8622}, mesh = {Humans ; Microcirculation ; Blood Flow Velocity ; Case-Control Studies ; Post-Acute COVID-19 Syndrome ; Anticoagulants ; *COVID-19 ; *Venous Thromboembolism ; Hemodynamics ; Hospitalization ; }, abstract = {BACKGROUND & OBJECTIVE: To quantify the hemodynamic and thrombotic effect of COVID-19 on the eye microcirculation of patients with thromboprophylaxis, shortly after hospital discharge.

METHODS: This case-control study included 17 COVID-19 survivors (named "COVID-19 Group") and 17 healthy volunteers (named "Control Group"). Axial blood velocity (Vax) and percentage of occluded vessels (POV) were quantified by Conjunctival Video Capillaroscopy (CVC). Microvessels were identified and classified as "capillaries" (CAP), "postcapillary venules of size 1" (PC1), and "postcapillary venules of size 2" (PC2).

RESULTS: The COVID-19 Group did not differ significantly in basic demographics from the Control Group. In the COVID-19 Group, there was a statistically significant (p < 0.001) reduction of Vax (39%, 49% and 47%, for CAP, PC1, and PC2, respectively) in comparison to the Control Group and a sizeable (p < 0.001) increase of POV (600%) in comparison to the Control Group.

CONCLUSIONS: COVID-19 not only reduces significantly axial blood velocity in the capillaries and postcapillary venules of the eye but has also a devastating effect on microthrombosis (POV) despite thromboprophylaxis treatment. This gives a possible explanation for long COVID and a hint about the existence of a possibly unknown coagulation factor.}, } @article {pmid35911550, year = {2022}, author = {Sze, S and Pan, D and Moss, AJ and Ong, CK and Pareek, M and Squire, IB and Clark, AL}, title = {Overstimulation of the ergoreflex-A possible mechanism to explain symptoms in long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {940832}, pmid = {35911550}, issn = {2297-055X}, abstract = {Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID.}, } @article {pmid35911387, year = {2022}, author = {Damanti, S and Cilla, M and Cilona, M and Fici, A and Merolla, A and Pacioni, G and De Lorenzo, R and Martinenghi, S and Vitali, G and Magnaghi, C and Fumagalli, A and Gennaro Mazza, M and Benedetti, F and Tresoldi, M and Rovere Querini, P}, title = {Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {834887}, pmid = {35911387}, issn = {2296-858X}, abstract = {BACKGROUND: A motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals.

METHODS: This was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia.

RESULTS: A total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23-1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B -5.63, 95% CI -8.39 to -2.87, p < 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10-15.13, p = 0.003), impaired muscle performance (SPPB: B -3.47, 95% CI -6.33 to -0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52-619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37-813413358.35, p < 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87-1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32-8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17-12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44-1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009).

CONCLUSION: The precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.}, } @article {pmid35910083, year = {2022}, author = {James, LM and Georgopoulos, AP}, title = {At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.}, journal = {Neuroscience insights}, volume = {17}, number = {}, pages = {26331055221114817}, pmid = {35910083}, issn = {2633-1055}, abstract = {Several foreign antigens such as those derived from viruses and bacteria have been linked to long-term deleterious effects on the brain and other organs; yet, health outcomes subsequent to foreign antigen exposure vary depending in large part on the host's immune system, in general, and on human leukocyte antigen (HLA) composition, in particular. Here we first provide a brief description of 3 conditions characterized by persistent long-term symptoms, namely long-COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Gulf War Illness (GWI), followed by a brief overview of the role of HLA in the immune response to foreign antigens. We then discuss our Persistent Antigen (PA) hypothesis and highlight associations between antigen persistence due to HLA-antigen incongruence and chronic health conditions in general and the 3 "long" diseases above in particular. This review is not intended to cover the breadth and depth of symptomatology of those diseases but is specifically focused on the hypothesis that the presence of persistent antigens underlies their pathogenesis.}, } @article {pmid35909366, year = {2022}, author = {Parums, DV}, title = {Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {28}, number = {}, pages = {e937927}, pmid = {35909366}, issn = {1643-3750}, mesh = {Adenoviruses, Human ; Adult ; *COVID-19/complications ; Child ; Humans ; Pandemics/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The range of long-term clinical conditions following SARS-CoV-2 infection in adults is now recognized. However, the prevalence, presentation, and risk factors for long COVID, or post-COVID-19, in children are less well understood because there have been few follow-up studies or long-term clinical trials in children with COVID-19. However, recent studies have shown that children with mild or asymptomatic COVID-19 may develop long-term sequelae that include cough, fatigue, and lethargy. The incidence and severity of common childhood respiratory viruses have changed in the past year, including respiratory syncytial virus (RSV). Hepatitis of unknown cause in children with SARS-CoV-2 infection is increasingly reported. Although both a viral cause and an autoimmune cause have been proposed, adenovirus type 41 infection is of current interest. These findings support immunization programs for SARS-CoV-2 in children, and infection surveillance and monitoring of the changing patterns and severity of other pediatric viral infections, including adenovirus type 41 and RSV, to develop and administer effective vaccines. This Editorial aims to highlight what is currently known of the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infection in children and the changing epidemiology and pathogenesis of previously common childhood viral infections now driven by the COVID-19 pandemic.}, } @article {pmid35908724, year = {2022}, author = {de Oliveira, JF and de Ávila, RE and de Oliveira, NR and da Cunha Severino Sampaio, N and Botelho, M and Gonçalves, FA and Neto, CJF and de Almeida Milagres, AC and Gomes, TCC and Pereira, TL and de Souza, RP and Molina, I}, title = {Persistent symptoms, quality of life, and risk factors in long COVID: a cross-sectional study of hospitalized patients in Brazil.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {122}, number = {}, pages = {1044-1051}, pmid = {35908724}, issn = {1878-3511}, mesh = {Brazil/epidemiology ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Dysgeusia ; Fatigue/epidemiology/etiology ; Humans ; Quality of Life ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: COVID-19 has been associated with long-term consequences to patient wellness and quality of life. Data on post-COVID-19 conditions are scarce in developing countries. This study aimed to investigate long COVID in a cohort of hospitalized patients in Brazil.

METHODS: Surviving patients discharged from the hospital between July 1, 2020 and March 31, 2021 were assessed between 2 and 12 months after acute onset of COVID-19. The outcomes were the prevalence of persistent symptoms, risk factors associated with long COVID, and quality of life as assessed by the EuroQol 5D-3L questionnaire.

RESULTS: Of 439 participants, most (84%) reported at least one long COVID symptom, at a median of 138 days (interquartile range [IQR] 90-201) after disease onset. Fatigue (63.1%), dyspnea (53.7%), arthralgia (56.1%), and depression/anxiety (55.1%) were the most prevalent symptoms. In multivariate analysis, dysgeusia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.18-3.44, P <0.001) and intensive care unit (ICU) admission (OR 2.6, 95% CI 1.19-6.56, P = 0.03) were independently associated with long COVID. Fifty percent of patients reported a worsened clinical condition and quality of life.

CONCLUSION: Long-term outcomes of SARS-CoV-2 infection in a low- to middle-income country were relevant. Fatigue was the most common persistent symptom. ICU admission was an independent factor associated with long COVID. Dysgeusia could be a potential predictor of long COVID.}, } @article {pmid35908177, year = {2022}, author = {Mantovani, E and Tamburin, S}, title = {D2/D3 Receptor Agonism: Paving the Way for a New Therapeutic Target for Taste Disorders in Parkinson's Disease and Other Conditions?.}, journal = {The international journal of neuropsychopharmacology}, volume = {25}, number = {11}, pages = {933-935}, pmid = {35908177}, issn = {1469-5111}, mesh = {Humans ; Aged ; Pramipexole ; Dopamine Agonists/therapeutic use ; Receptors, Dopamine D3 ; *Parkinson Disease/complications/drug therapy/physiopathology ; Dopamine ; Healthy Volunteers ; *COVID-19 ; Taste ; Quality of Life ; Benzothiazoles ; Taste Disorders/drug therapy/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Chemosensory (i.e., olfaction and taste) dysfunction is common in neurodegenerative (e.g., Parkinson's disease, Alzheimer's disease, and dementia), psychiatric (e.g., depression, bipolar disorders, other conditions), and postinfectious (i.e., long COVID) diseases and in the elderly. Despite its impact on patients' quality of life, no established treatment for taste disorders exists so far. A recent report on the effect of pramipexole, a D2/D3 agonist, on taste performance in healthy participants provides support for a new potential therapeutic target for taste dysfunction to be tested in future randomized, placebo-controlled, clinical trials across several populations reporting gustatory symptoms.}, } @article {pmid35907815, year = {2022}, author = {Blackmon, K and Day, GS and Powers, HR and Bosch, W and Prabhakaran, D and Woolston, D and Pedraza, O}, title = {Neurocognitive screening in patients following SARS-CoV-2 infection: tools for triage.}, journal = {BMC neurology}, volume = {22}, number = {1}, pages = {285}, pmid = {35907815}, issn = {1471-2377}, mesh = {*COVID-19/complications/diagnosis ; Cross-Sectional Studies ; Hospitalization ; Humans ; SARS-CoV-2 ; Triage ; }, abstract = {BACKGROUND: Cognitive complaints are common in patients recovering from Coronavirus Disease 2019 (COVID-19), yet their etiology is often unclear. We assess factors that contribute to cognitive impairment in ambulatory versus hospitalized patients during the sub-acute stage of recovery.

METHODS: In this cross-sectional study, participants were prospectively recruited from a hospital-wide registry. All patients tested positive for SARS-CoV-2 infection using a real-time reverse transcriptase polymerase-chain-reaction assay. Patients ≤ 18 years-of-age and those with a pre-existing major neurocognitive disorder were excluded. Participants completed an extensive neuropsychological questionnaire and a computerized cognitive screen via remote telemedicine platform. Rates of subjective and objective neuropsychological impairment were compared between the ambulatory and hospitalized groups. Factors associated with impairment were explored separately within each group.

RESULTS: A total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests 24 ± 22 days following laboratory confirmation of SARS-CoV-2 infection. Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27-40%), without differences between the groups. However, hospitalized patients showed higher rates of objective impairment in visual memory (30% vs. 4%; p = 0.001) and psychomotor speed (41% vs. 15%; p = 0.008). Objective cognitive test performance was associated with anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group.

CONCLUSIONS: Focal cognitive deficits are more common in hospitalized than ambulatory patients. Cognitive performance is associated with neuropsychiatric symptoms in ambulatory but not hospitalized patients. Objective neurocognitive measures can provide essential information to inform neurologic triage and should be included as endpoints in clinical trials.}, } @article {pmid35907120, year = {2022}, author = {Bergmans, RS and Chambers-Peeple, K and Aboul-Hassan, D and Dell'Imperio, S and Martin, A and Wegryn-Jones, R and Xiao, LZ and Yu, C and Williams, DA and Clauw, DJ and DeJonckheere, M}, title = {Opportunities to Improve Long COVID Care: Implications from Semi-structured Interviews with Black Patients.}, journal = {The patient}, volume = {15}, number = {6}, pages = {715-728}, pmid = {35907120}, issn = {1178-1661}, support = {P30 ES017885/ES/NIEHS NIH HHS/United States ; T32 AR007080/AR/NIAMS NIH HHS/United States ; }, mesh = {Adult ; Humans ; United States ; Female ; Male ; *COVID-19/epidemiology ; COVID-19 Testing ; Black People ; *Physicians ; Qualitative Research ; Post-Acute COVID-19 Syndrome ; Black or African American ; }, abstract = {BACKGROUND: Long coronavirus disease (COVID) is an emerging condition that could considerably burden healthcare systems. Prior qualitative studies characterize the experience of having long COVID, which is valuable for informing care strategies. However, evidence comes from predominantly White samples. This is a concern because underrepresentation of Black patients in research and intervention development contribute to racial inequities.

OBJECTIVE: To facilitate racial equity in long COVID care, the purpose of this qualitative study was to inform the development of care strategies that are responsive to the experiences and perspectives of Black patients with long COVID in the United States of America.

METHODS: Using convenience sampling, we conducted race-concordant, semi-structured, and open-ended interviews with Black adults (80% female, mean age = 39) who had long COVID. We transcribed and anonymized the recorded interviews. We analyzed the transcripts using inductive, thematic analysis. Theme development focused on who can help or hinder strategies for reducing health inequities, what should be done to change care policies or treatment strategies, and when are the critical timepoints for intervention.

RESULTS: We developed four main themes. Participants reported challenges before and after COVID testing. Many participants contacted primary care physicians as a first step for long COVID treatment. However, not all respondents had positive experiences and at times felt dismissed. Without a qualifying diagnosis, participants could not obtain disability benefits, which negatively influenced their employment and increased financial hardship.

CONCLUSIONS: There are possible targets for improving long COVID care, from COVID testing through to long-term treatment plans. There is a need to increase long COVID awareness among physicians. Diagnosis and a standardized treatment plan could help patients avoid unnecessary healthcare utilization and obtain comprehensive support.}, } @article {pmid35906952, year = {2023}, author = {Altersberger, M and Goliasch, G and Khafaga, M and Schneider, M and Cho, Y and Winkler, R and Funk, GC and Binder, T and Huber, G and Zwick, RH and Genger, M}, title = {Echocardiography and Lung Ultrasound in Long COVID and Post-COVID Syndrome, a Review Document of the Austrian Society of Pneumology and the Austrian Society of Ultrasound in Medicine.}, journal = {Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine}, volume = {42}, number = {2}, pages = {269-277}, pmid = {35906952}, issn = {1550-9613}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *Pulmonary Medicine ; Austria ; *COVID-19 ; Echocardiography ; Lung/diagnostic imaging ; }, abstract = {Lung ultrasound has the potential to enable standardized follow-up without radiation exposure and with lower associated costs in comparison to CT scans. It is a valuable tool to follow up on patients after a COVID-19 infection and evaluate if there is pulmonary fibrosis developing. Echocardiography, including strain imaging, is a proven tool to assess various causes of dyspnea and adds valuable information in the context of long COVID care. Including two-dimensional (2D) strain imaging, a better comprehension of myocardial damage in post-COVID syndrome can be made. Especially 2D strain imaging (left and the right ventricular strain) can provide information about prognosis.}, } @article {pmid35904783, year = {2022}, author = {Ioannou, GN and Baraff, A and Fox, A and Shahoumian, T and Hickok, A and O'Hare, AM and Bohnert, ASB and Boyko, EJ and Maciejewski, ML and Bowling, CB and Viglianti, E and Iwashyna, TJ and Hynes, DM}, title = {Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System.}, journal = {JAMA network open}, volume = {5}, number = {7}, pages = {e2224359}, pmid = {35904783}, issn = {2574-3805}, support = {IK6 HX003395/HX/HSRD VA/United States ; }, mesh = {Aged ; Aged, 80 and over ; *COVID-19/complications/epidemiology ; COVID-19 Testing ; Delivery of Health Care ; Documentation ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; *Veterans ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Some persons infected with SARS-CoV-2 experience symptoms or impairments many months after acute infection.

OBJECTIVES: To determine the rates, clinical setting, and factors associated with documented receipt of COVID-19-related care 3 or more months after acute infection.

This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants included persons with a positive SARS-CoV-2 test between February 1, 2020, and April 30, 2021, who were still alive 3 months after infection and did not have evidence of reinfection. Data analysis was performed from February 2020 to December 2021.

EXPOSURES: Positive SARS-CoV-2 test.

MAIN OUTCOMES AND MEASURES: Rates and factors associated with documentation of COVID-19-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (U07.1, Z86.16, U09.9, and J12.82) 3 or more months after acute infection (hereafter, long-COVID care), with follow-up extending to December 31, 2021.

RESULTS: Among 198 601 SARS-CoV-2-positive persons included in the study, the mean (SD) age was 60.4 (17.7) years, 176 942 individuals (89.1%) were male, 133 924 (67.4%) were White, 44 733 (22.5%) were Black, and 19 735 (9.9%) were Hispanic. During a mean (SD) follow-up of 13.5 (3.6) months, long-COVID care was documented in a wide variety of clinics, most commonly primary care and general internal medicine (18 634 of 56 310 encounters [33.1%]), pulmonary (7360 of 56 310 encounters [13.1%]), and geriatrics (5454 of 56 310 encounters [9.7%]). Long-COVID care was documented in 26 745 cohort members (13.5%), with great variability across geographical regions (range, 10.8%-18.1%) and medical centers (range, 3.0%-41.0%). Factors significantly associated with documented long-COVID care included older age, Black or American Indian/Alaska Native race, Hispanic ethnicity, geographical region, high Charlson Comorbidity Index score, having documented symptoms at the time of acute infection (adjusted odds ratio [AOR], 1.71; 95% CI, 1.65-1.78) and requiring hospitalization (AOR, 2.60; 95% CI, 2.51-2.69) or mechanical ventilation (AOR, 2.46; 95% CI, 2.26-2.69). Patients who were fully vaccinated at the time of infection were less likely to receive long-COVID care (AOR, 0.78; 95% CI, 0.68-0.90).

CONCLUSIONS AND RELEVANCE: Long-COVID care was documented in a variety of clinical settings, with great variability across regions and medical centers and was documented more commonly in older persons, those with higher comorbidity burden, those with more severe acute COVID-19 presentation and those who were unvaccinated at the time of infection. These findings provide support and guidance for health care systems to develop systematic approaches to the evaluation and management of patients who may be experiencing long COVID.}, } @article {pmid35904700, year = {2022}, author = {Jimeno-Almazán, A and Martínez-Cava, A and Buendía-Romero, Á and Franco-López, F and Sánchez-Agar, JA and Sánchez-Alcaraz, BJ and Tufano, JJ and Pallarés, JG and Courel-Ibáñez, J}, title = {Relationship between the severity of persistent symptoms, physical fitness, and cardiopulmonary function in post-COVID-19 condition. A population-based analysis.}, journal = {Internal and emergency medicine}, volume = {17}, number = {8}, pages = {2199-2208}, pmid = {35904700}, issn = {1970-9366}, support = {35110/2020//Hospital Médico Virgen de la Caridad/ ; }, mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology ; Stroke Volume ; Ventricular Function, Left ; Physical Fitness ; Fatigue/etiology ; Dyspnea/etiology ; }, abstract = {The aim of this study was to determine the relationship between physical fitness, cardiopulmonary function and patient-reported severity of symptoms in people with post-COVID-19 condition. We examined ambulatory patients (n = 72) with post-COVID-19 condition who had a chronic symptomatic phase lasting > 12 weeks from the onset of symptoms, but had not been hospitalized for acute COVID-19. A comprehensive medical screening was conducted, including clinical history, symptomatology, comorbidities, body composition and physical activity levels. We then identified the relationship between physical fitness (cardiorespiratory fitness and muscular strength), cardiopulmonary function (echocardiographic and spirometry parameters) and patient-reported severity of symptoms (fatigue, dyspnea, health-related quality of life, anxiety, and depression). Age, body mass index, sex, number of comorbidities and duration of symptoms were included as potential confounders. Results showed that greater physical fitness and cardiopulmonary function were associated with lower severity of symptoms in people with post-COVID-19 condition. Cardiorespiratory fitness, lower-limb muscle strength, maximal voluntary ventilation and left ventricular ejection fraction account for reducing fatigue and dyspnea. Greater physical activity levels were associated with fewer symptoms and less-severe fatigue and dyspnea. In conclusion, preserving better cardiopulmonary health and physical condition during the course of the disease-even in mild cases-was related to a lower intensity of symptoms in non-hospitalized people with post-COVID-19 condition. It is probable that exercise and physical conditioning are valuable pre- and post-COVID-19 countermeasures that could help decrease the severity, not only of acute infection, but of post-COVID-19 persistent symptoms and prognosis.}, } @article {pmid35902858, year = {2022}, author = {Plekhanova, T and Rowlands, AV and Evans, RA and Edwardson, CL and Bishop, NC and Bolton, CE and Chalmers, JD and Davies, MJ and Daynes, E and Dempsey, PC and Docherty, AB and Elneima, O and Greening, NJ and Greenwood, SA and Hall, AP and Harris, VC and Harrison, EM and Henson, J and Ho, LP and Horsley, A and Houchen-Wolloff, L and Khunti, K and Leavy, OC and Lone, NI and Marks, M and Maylor, B and McAuley, HJC and Nolan, CM and Poinasamy, K and Quint, JK and Raman, B and Richardson, M and Sargeant, JA and Saunders, RM and Sereno, M and Shikotra, A and Singapuri, A and Steiner, M and Stensel, DJ and Wain, LV and Whitney, J and Wootton, DG and Brightling, CE and Man, WD and Singh, SJ and Yates, T and , }, title = {Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.}, journal = {The international journal of behavioral nutrition and physical activity}, volume = {19}, number = {1}, pages = {94}, pmid = {35902858}, issn = {1479-5868}, support = {MR/V020536/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Accelerometry/methods ; Aftercare ; Aged ; *COVID-19 ; *Diabetes Mellitus, Type 2/therapy ; Exercise ; Female ; Hospitalization ; Hospitals ; Humans ; Male ; Patient Discharge ; Sleep ; }, abstract = {BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms.

METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators.

RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes.

CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.}, } @article {pmid35902374, year = {2022}, author = {Karkala, A and Moschonas, S and Sykas, G and Karagianni, M and Gilou, S and Papaefthymiou, O and Kourtidou-Papadeli, C}, title = {Sleep Quality and Mental Health Consequences of COVID-19 Pandemic in the Aviation Community in Greece.}, journal = {Journal of occupational and environmental medicine}, volume = {64}, number = {9}, pages = {e567-e574}, pmid = {35902374}, issn = {1536-5948}, mesh = {*Aviation ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Fatigue/epidemiology/etiology ; Female ; Greece/epidemiology ; Humans ; Mental Health ; Pandemics ; Sleep Quality ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The aim of this study was to assess the mental health and sleep quality of aviation workers in Greece during the pandemic.

METHODS: A cross-sectional study of aviation workers in Greece was conducted.

RESULTS: Sleep disturbances were observed in 25.4% of our 548 participants, whereas 8.2% and 5.8% reported at least mild depressive and anxiety symptoms, respectively. The impact of the pandemic on their mental health was their primary concern, which increased for many active pilots according to their workload. Those infected mainly faced daily tiredness and fatigue. Smoking habits and high body mass index were a predisposition for more physical symptoms. Cabin crew and women generally yielded worse scores than the other groups.

CONCLUSION: Fear of infection could explain mental health issues, whereas physical symptoms of those infected could be attributed to long-COVID (coronavirus disease) syndrome. Flight attendants' lower ratings may be due to more occupational exposure.}, } @article {pmid35901492, year = {2022}, author = {Lechner, M and Liu, J and Counsell, N and Gillespie, D and Chandrasekharan, D and Ta, NH and Jumani, K and Gupta, R and Rao-Merugumala, S and Rocke, J and Williams, C and Tetteh, A and Amnolsingh, R and Khwaja, S and Batterham, RL and Yan, CH and Treibel, TA and Moon, JC and Woods, J and Brunton, R and Boardman, J and Paun, S and Eynon-Lewis, N and Kumar, BN and Jayaraj, S and Hopkins, C and Philpott, C and Lund, VJ}, title = {The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.}, journal = {Rhinology}, volume = {60}, number = {3}, pages = {188-199}, doi = {10.4193/Rhin21.470}, pmid = {35901492}, issn = {0300-0729}, support = {FS/19/35/34374/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; Smell ; *COVID-19/complications ; Anosmia/etiology ; Olfactory Training ; *Olfaction Disorders/etiology/diagnosis ; }, abstract = {BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted.

METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants.

RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia.

CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.}, } @article {pmid35901463, year = {2022}, author = {Ng, R and Vargas, G and Jashar, DT and Morrow, A and Malone, LA}, title = {Neurocognitive and Psychosocial Characteristics of Pediatric Patients With Post-Acute/Long-COVID: A Retrospective Clinical Case Series.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {37}, number = {8}, pages = {1633-1643}, pmid = {35901463}, issn = {1873-5843}, mesh = {Humans ; Child ; Neuropsychological Tests ; *COVID-19/complications ; Retrospective Studies ; Attention ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Studies suggest a large number of patients have persistent symptoms following COVID-19 infection-a condition termed "long COVID." Although children and parents often report cognitive difficulties after COVID, very few if any studies have been published including neuropsychological testing.

METHODS: A retrospective chart review was completed for the first 18 patients referred for a neuropsychological evaluation from a multidisciplinary pediatric post-COVID clinic. The neuropsychological screening battery assessed verbal fluency and category switching, attention, working memory, processing speed, and verbal learning and memory. Patients' caregivers also completed standardized questionnaires regarding day-to-day mood and behavior.

RESULTS: At intake, the most common neurologic symptoms reported by caregivers were attention problems (83.3%), fatigue/lethargy (77.7%), sleep disturbance (77.7%), dizziness/vertigo (72.2%), and headaches (72.2%). On rating scales, most caregivers endorsed concerns for depressed mood and anxiety (14/15 and 12/15). A large proportion of patients had difficulties with attention (9/18) and depressed mood/anxiety (13/18) before COVID. On cognitive testing, the majority of the patients performed within or above broad average range (≥16th percentile) across most domains. However, a little over half of the patients performed below average on auditory attention measures.

CONCLUSIONS: Within our clinically referred sample, children who reported lingering cognitive symptoms after COVID-19 often had a preexisting history of attention and/or mood and anxiety concerns. Many of these patients performed below average in attention testing, but it remains to be seen whether this was due to direct effects of COVID, physical symptoms, and/or preexisting difficulties with attention or mood/anxiety.}, } @article {pmid35898449, year = {2022}, author = {Bonyek-Silva, I and Cerqueira-Silva, T and Nunes, S and Machado, AFA and Cruz, MRS and Pereira, B and Estrela, L and Silva, J and Isis, A and Barral, A and Oliveira, PRS and Khouri, R and Serezani, CH and Brodskyn, C and Caldas, JR and Barral-Netto, M and Boaventura, V and Tavares, NM}, title = {Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {896378}, pmid = {35898449}, issn = {1664-2392}, support = {R01 DK122147/DK/NIDDK NIH HHS/United States ; R01 HL124159/HL/NHLBI NIH HHS/United States ; R21 AI149207/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19/complications ; *Diabetes Mellitus ; Hospitalization ; Humans ; Interleukin-6/*biosynthesis ; *Prediabetic State/complications ; }, abstract = {AIMS: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19.

MATERIALS AND METHODS: We compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization.

RESULTS: Patients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms.

CONCLUSIONS: PDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.}, } @article {pmid35898346, year = {2022}, author = {Peluso, MJ and Deveau, TM and Munter, SE and Ryder, D and Buck, A and Beck-Engeser, G and Chan, F and Lu, S and Goldberg, SA and Hoh, R and Tai, V and Torres, L and Iyer, NS and Deswal, M and Ngo, LH and Buitrago, M and Rodriguez, A and Chen, JY and Yee, BC and Chenna, A and Winslow, JW and Petropoulos, CJ and Deitchman, AN and Hellmuth, J and Spinelli, MA and Durstenfeld, MS and Hsue, PY and Kelly, JD and Martin, JN and Deeks, SG and Hunt, PW and Henrich, TJ}, title = {Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {35898346}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K24 AI145806/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; }, abstract = {UNLABELLED: The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. In a cohort of 280 adults with prior SARS-CoV-2 infection, we observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4 months following initial diagnosis were independently associated with serological evidence of recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen IgG levels, but not with ongoing EBV viremia. Evidence of EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52) and tended to have less severe (>5 symptoms reported) LC (OR 0.44). Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.

SUMMARY: The authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence of recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with a decreased risk of Long COVID.}, } @article {pmid35898334, year = {2022}, author = {Mohan, SA and Fadzaily, ZS and Abdullah Hashim, SH}, title = {Spontaneous Haemothorax in a Patient with COVID-19.}, journal = {Case reports in medicine}, volume = {2022}, number = {}, pages = {8275326}, pmid = {35898334}, issn = {1687-9627}, abstract = {The global pandemic of COVID-19 is caused by SARS-CoV-2 virus. We continue to discover the wide spectrum of complications associated with COVID-19. Some well-known complications include pneumonia, acute respiratory distress syndrome, pneumothorax, disseminated intravascular coagulation (DIC), chronic fatigue, multiorgan dysfunction, and long COVID-19 syndrome. We report a rare case of a 51-year-old man with severe COVID-19 pneumonia who developed haemorrhagic shock secondary to spontaneous haemothorax after 17 days of hospitalisation. Clinicians should be aware of such occurrence, and hence, high clinical suspicion, prompt recognition of signs and symptoms of shock, and adequate resuscitation will improve the outcomes of patients.}, } @article {pmid35897448, year = {2022}, author = {Aghaei, A and Zhang, R and Taylor, S and Tam, CC and Yang, CH and Li, X and Qiao, S}, title = {Social Life of Females with Persistent COVID-19 Symptoms: A Qualitative Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {15}, pages = {}, pmid = {35897448}, issn = {1660-4601}, support = {R01AI127203-5S1/NH/NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Female ; Humans ; Qualitative Research ; Social Stigma ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent COVID-19 symptoms (long COVID) may bring challenges to long haulers' social lives. Females may endure more profound impacts given their special social roles and existing structural inequality. This study explores the effects of long COVID on the social life of female long haulers. We conducted semi-structured interviews via Zoom between April and June 2021 with 15 female long haulers in the United States, purposely recruited from Facebook and Slack groups and organization websites related to long COVID. Interviews were audio-recorded and transcribed verbatim with consent. The interview data were managed using MAXQDA and examined by thematic analysis. Long COVID negatively affected female long haulers' social lives by causing physical limitations, economic issues, altered social relationships, social roles' conflicts, and social stigma. Long COVID prevented female long haulers' recovery process. Physical limitations altered their perceptions on body, and family-work conflicts caused tremendous stress. They also experienced internalized stigma and job insecurities. This study provides insights into challenges that COVID-19 female long haulers could face in their return to normal social life, underscoring the vulnerability of females affected by long COVID due to significant alterations in their social lives. Shifting to new methods of communication, especially social media, diminished the adverse effects of long COVID (e.g., social isolation).}, } @article {pmid35896202, year = {2022}, author = {Wise, J}, title = {Long covid: Hair loss and sexual dysfunction are among wider symptoms, study finds.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o1887}, doi = {10.1136/bmj.o1887}, pmid = {35896202}, issn = {1756-1833}, mesh = {Alopecia/etiology ; *COVID-19/complications ; Humans ; *Sexual Dysfunction, Physiological/etiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35896188, year = {2022}, author = {Tan, BKJ and Han, R and Zhao, JJ and Tan, NKW and Quah, ESH and Tan, CJ and Chan, YH and Teo, NWY and Charn, TC and See, A and Xu, S and Chapurin, N and Chandra, RK and Chowdhury, N and Butowt, R and von Bartheld, CS and Kumar, BN and Hopkins, C and Toh, ST}, title = {Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {e069503}, pmid = {35896188}, issn = {1756-1833}, support = {P20 GM103554/GM/NIGMS NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Female ; Humans ; *Olfaction Disorders/etiology ; Prognosis ; Smell ; Taste ; Taste Disorders/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021.

REVIEW METHODS: Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included.

DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery.

MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste.

RESULTS: 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I[2]=70%, τ[2]=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I[2]=67%, τ[2]=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I[2]=0.0-77.2%, τ[2]=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I[2]=0.0-72.1%, τ[2]=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I[2]=20%, τ[2]=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I[2]=78%, τ[2]=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I[2]=10%, τ[2]<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I[2]=0%, τ[2]<0.001) were less likely to recover their sense of smell.

CONCLUSIONS: A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid.

PROSPERO CRD42021283922.}, } @article {pmid35895564, year = {2022}, author = {Falus, A}, title = {[Coronavirus pandemic - the COVID-19 kaleidoscope today (May, 2022)].}, journal = {Orvosi hetilap}, volume = {163}, number = {24}, pages = {935-942}, doi = {10.1556/650.2022.32574}, pmid = {35895564}, issn = {1788-6120}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The article attempts to review the principal epidemiological data of the coronavirus pandemic (COVID-19) based on the rapidly changing and expanding international and domestic literature. The review covers the so-called ,,long COVID-19 as well as the latest pharmacological and immunotherapeutic developments. The manuscript deals with the future of innovative vaccinology, the so-called 'pan-vaccines' developed through artificial intelligences and nano technology.}, } @article {pmid35893881, year = {2022}, author = {Ghanem, J and Passadori, A and Severac, F and Dieterlen, A and Geny, B and Andrès, E}, title = {Effects of Rehabilitation on Long-COVID-19 Patient's Autonomy, Symptoms and Nutritional Observance.}, journal = {Nutrients}, volume = {14}, number = {15}, pages = {}, pmid = {35893881}, issn = {2072-6643}, mesh = {*COVID-19/complications ; Fatigue/complications ; Humans ; *Malnutrition/diagnosis ; Nutrition Assessment ; Nutritional Status ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Despite significant improvements in COVID-19 therapy, many patients still present with persistent symptoms and quality-of-life alterations. The aim of this study was to simultaneously investigate the long-term evolution of autonomy, malnutrition and long-lasting symptoms in people infected with COVID-19 and hospitalized in the ICU. Method: Patients’ clinical characteristics; extent of their loss of autonomy based on “Autonomie Gérontologie Groupes Iso-Ressources” (AG-GIR) classification; nutritional status while following the French and Global Leadership Initiative on Malnutrition (GLIM) recommendations; and symptom evolutions before infection, during hospitalization and rehabilitation, and up to 6 months after returning home were determined in thirty-seven patients. Results: Prior to a COVID-19 infection, all patients were autonomous, but upon admission to the rehabilitation center (CRM), 39% of them became highly dependent. After discharge from the center and 6 months after returning home, only 6 and 3%, respectively, still required considerable assistance. Of these thirty-seven patients, 11% were moderately malnourished and 81% presented with severe malnutrition, with a significant correlation being observed between malnutrition and autonomy (p < 0.05). Except for fatigue, which persisted in 70% of the patients 6 months after discharge from rehabilitation, all other symptoms decreased significantly. Conclusions: This study shows a striking decrease in autonomy associated with malnutrition after hospitalization for a COVID-19 infection and a clear beneficial effect from personalized rehabilitation. However, although almost all patients regained autonomy 6 months after returning home, they often still suffer from fatigue. Patient compliance with their nutritional recommendations deserves further improvement, preferably through personalized and persistent follow-up with the patient.}, } @article {pmid35893413, year = {2022}, author = {Joris, M and Pincemail, J and Colson, C and Joris, J and Calmes, D and Cavalier, E and Misset, B and Guiot, J and Minguet, G and Rousseau, AF}, title = {Exercise Limitation after Critical Versus Mild COVID-19 Infection: A Metabolic Perspective.}, journal = {Journal of clinical medicine}, volume = {11}, number = {15}, pages = {}, pmid = {35893413}, issn = {2077-0383}, abstract = {Exercise limitation in COVID-19 survivors is poorly explained. In this retrospective study, cardiopulmonary exercise testing (CPET) was coupled with an oxidative stress assessment in COVID-19 critically ill survivors (ICU group). Thirty-one patients were included in this group. At rest, their oxygen uptake (VO2) was elevated (8 [5.6-9.7] mL/min/kg). The maximum effort was reached at low values of workload and VO2 (66 [40.9-79.2]% and 74.5 [62.6-102.8]% of the respective predicted values). The ventilatory equivalent for carbon dioxide remained within normal ranges. Their metabolic efficiency was low: 15.2 [12.9-17.8]%. The 50% decrease in VO2 after maximum effort was delayed, at 130 [120-170] s, with a still-high respiratory exchange ratio (1.13 [1-1.2]). The blood myeloperoxidase was elevated (92 [75.5-106.5] ng/mL), and the OSS was altered. The CPET profile of the ICU group was compared with long COVID patients after mid-disease (MLC group) and obese patients (OB group). The MLC patients (n = 23) reached peak workload and predicted VO2 values, but their resting VO2, metabolic efficiency, and recovery profiles were similar to the ICU group to a lesser extent. In the OB group (n = 15), no hypermetabolism at rest was observed. In conclusion, the exercise limitation after a critical COVID-19 bout resulted from an altered metabolic profile in the context of persistent inflammation and oxidative stress. Altered exercise and metabolic profiles were also observed in the MLC group. The contribution of obesity on the physiopathology of exercise limitation after a critical bout of COVID-19 did not seem relevant.}, } @article {pmid35893119, year = {2022}, author = {Raciti, L and De Luca, R and Raciti, G and Arcadi, FA and Calabrò, RS}, title = {The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {10}, number = {3}, pages = {}, pmid = {35893119}, issn = {2076-3271}, mesh = {Adult ; Amides ; *COVID-19/complications ; Ethanolamines ; Female ; Humans ; Male ; Middle Aged ; Palmitic Acids ; Quality of Life ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID. Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.}, } @article {pmid35893072, year = {2022}, author = {Fernández-de-Las-Peñas, C and Giordano, R and Díaz-Gil, G and Gil-Crujera, A and Gómez-Sánchez, SM and Ambite-Quesada, S and Arendt-Nielsen, L}, title = {Are Pain Polymorphisms Associated with the Risk and Phenotype of Post-COVID Pain in Previously Hospitalized COVID-19 Survivors?.}, journal = {Genes}, volume = {13}, number = {8}, pages = {}, pmid = {35893072}, issn = {2073-4425}, mesh = {Adult ; Aged ; *COVID-19/complications/genetics ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; *Neuralgia/genetics/virology ; Phenotype ; Polymorphism, Single Nucleotide ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objective: To investigate the association of different, selected pain polymorphisms with the presence of de novo long-COVID pain symptoms and to analyze the association between these polymorphisms with clinical, sensory-related, cognitive and psychological variables in COVID-19 survivors. Methods: Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) previously hospitalized COVID-19 survivors participated. Three genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva: OPRM1 (rs1799971), COMT (rs4680), BDNF (rs6265), and HTR1B (rs6296) by polymerase chain reactions in all participants. Further, clinical (intensity/duration of pain), sensory-related (sensitization-associated symptoms, neuropathic pain features), psychological (anxiety or depressive levels, sleep quality), and cognitive (catastrophizing, kinesiophobia) variables were collected in those COVID-19 survivors suffering from post-COVID pain. Analyses were carried out to associate clinical features with genotype. Results: Participants were assessed 17.8 ± 5.2 months after hospitalization. One hundred and seventeen (39.9%) experienced post-COVID pain (particularly of musculoskeletal origin). The distributions of the genotype variants of any SNP were not significantly different between COVID-19 survivors with and without long-term post-COVID pain (all, p > 0.178). No differences in sensitization-associated symptoms, neuropathic pain features, catastrophizing, kinesiophobia levels, anxiety and depressive levels or sleep quality according to the genotype variant in any SNPs were found. No effect of gender was identified. Conclusion: The four SNPs generally associated with pain did not appear to predispose to the development of de novo long-COVID pain symptoms in previously hospitalized COVID-19 survivors. The SNPs were not involved in the phenotypic features of post-COVID pain either.}, } @article {pmid35892542, year = {2022}, author = {Krouzecky, C and Aden, J and Hametner, K and Klaps, A and Kovacovsky, Z and Stetina, BU}, title = {Fantastic Beasts and Why It Is Necessary to Understand Our Relationship-Animal Companionship under Challenging Circumstances Using the Example of Long-Covid.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {15}, pages = {}, pmid = {35892542}, issn = {2076-2615}, abstract = {Studies in the field of human-animal interaction tend to highlight the positive results of the influence of animals on humans, which supports the popular belief that the human-animal bond positively affects humans' well-being ("pet-effect"). Nevertheless, contradictory results exist that seem especially visible since the COVID-19 pandemic, a prominent external stressor. Despite critical findings, individuals seem to want to believe in the beneficial effects of the human-animal relationship ("pet-effect paradox"). Based on this background, the present study aims to investigate this phenomenon using a mixed-method design. Therefore, animal caregivers were surveyed online and compared using psychometric measurements and open-ended questions. In this context, a special focus was placed on the additional stressor of Long-Covid and related concerns. The results demonstrate once more the existence of the "pet-effect paradox" due to a contradiction in the quantitative and qualitative results. At a quantitative level, the findings show additional burdens on animal caregivers who are confronted with multiple loads. However, the qualitative results indicate a belief in the beneficial effects of pets at the biopsychosocial level. Additionally, the data demonstrate a shift in focus away from the environment to oneself when affected by Long-Covid, which might affect the ability to care for an animal.}, } @article {pmid35892410, year = {2022}, author = {Tarantino, S and Graziano, S and Carducci, C and Giampaolo, R and Grimaldi Capitello, T}, title = {Cognitive Difficulties, Psychological Symptoms, and Long Lasting Somatic Complaints in Adolescents with Previous SARS-CoV-2 Infection: A Telehealth Cross-Sectional Pilot Study.}, journal = {Brain sciences}, volume = {12}, number = {8}, pages = {}, pmid = {35892410}, issn = {2076-3425}, abstract = {BACKGROUND: Few studies have evaluated cognitive functioning and mental health in children and adolescents who contracted the SARS-CoV-2 infection. We investigated the prevalence and association of neuropsychological difficulties, psychological symptoms, and self-reported long-COVID complaints in a sample of adolescents.

METHODS: Thirty-one adolescents infected by COVID-19 within 3-6 months prior to the assessment were included. Neuropsychological difficulties, psychological symptoms, and self-reported long-COVID complaints were evaluated using a checklist and a battery of multiple standardized measures, using a telehealth procedure. Symptoms during the infection were also detected.

RESULTS: We included 31 adolescents (23 girls, 8 boys; mean age 14.1, SD = 2). We found borderline scores in 32.3% and 45.2% of our sample for phonemic and category fluency, respectively. A high percentage of participants showed symptoms of depression (80.6%) and anxiety (61.3%). Fifty-eight percent reported at least one long-COVID symptom. The most common symptoms were headache and attention problems (58%). Subjects presenting numbness/weakness, fatigue, brain fog, or attention problems had higher scores in depression, anxiety, and post-traumatic stress symptoms (p ≤ 0.05).

CONCLUSION: This is a pilot study limited by the lack of control group. However, we found that cognitive, psychological, and physical symptoms were very common among adolescents recovered from COVID-19.}, } @article {pmid35892064, year = {2023}, author = {Sathish, T and Anton, MC}, title = {Persistence of new-onset diabetes in the post-acute phase of COVID-19.}, journal = {International journal of diabetes in developing countries}, volume = {43}, number = {1}, pages = {118-119}, pmid = {35892064}, issn = {0973-3930}, } @article {pmid35891696, year = {2022}, author = {Helmsdal, G and Hanusson, KD and Kristiansen, MF and Foldbo, BM and Danielsen, ME and Steig, BÁ and Gaini, S and Strøm, M and Weihe, P and Petersen, MS}, title = {Long COVID in the Long Run-23-Month Follow-up Study of Persistent Symptoms.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac270}, pmid = {35891696}, issn = {2328-8957}, abstract = {Symptoms of long coronavirus disease (COVID) were found in 38% of 170 patients followed for a median of 22.6 months. The most prevalent symptoms were fatigue, affected taste and smell, and difficulties remembering and concentrating. Predictors for long COVID were older age and number of symptoms in the acute phase. Long COVID may take many months, maybe years, to resolve.}, } @article {pmid35891466, year = {2022}, author = {Fernández-de-Las-Peñas, C and Valera-Calero, JA and Herrero-Montes, M and Del-Valle-Loarte, P and Rodríguez-Rosado, R and Ferrer-Pargada, D and Arendt-Nielsen, L and Parás-Bravo, P}, title = {The Self-Reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and PainDETECT Questionnaires in COVID-19 Survivors with Post-COVID Pain.}, journal = {Viruses}, volume = {14}, number = {7}, pages = {}, pmid = {35891466}, issn = {1999-4915}, mesh = {*COVID-19/complications/diagnosis ; Humans ; *Neuralgia/diagnosis/etiology ; Quality of Life ; Reproducibility of Results ; Self Report ; Surveys and Questionnaires ; Survivors ; }, abstract = {This study aimed to analyze correlations between Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS) and PainDETECT with proxies of sensitization, pain-related, or psychological/cognitive variables in coronavirus disease, 2019 (COVID-19) survivors exhibiting post-COVID pain. Demographic, clinical, psychological, cognitive, sensitization-associated symptoms, and health-related quality of life were collected in 146 survivors with post-COVID pain. The PainDETECT and S-LANSS questionnaires were used for assessing neuropathic pain-related symptoms. Patients were assessed with a mean of 18.8 (SD 1.8) months after hospitalization. Both questionnaires were positively associated with pain intensity (p < 0.05), anxiety (PainDETECT p < 0.05; S-LANSS p < 0.01), sensitization-associated symptoms (p < 0.01), catastrophism (p < 0.01), and kinesiophobia (p < 0.01) and negatively associated with quality of life (PainDETECT p < 0.05; S-LANSS p < 0.01). Depressive levels were associated with S-LANSS (p < 0.05) but not with PainDETECT. The stepwise regression analyses revealed that 47.2% of S-LANSS was explained by PainDETECT (44.6%), post-COVID pain symptoms duration (1.7%), and weight (1.1%), whereas 51.2% of PainDETECT was explained by S-LANSS (44.6%), sensitization-associated symptoms (5.4%), and anxiety levels (1.2%). A good convergent association between S-LANSS and PainDETECT was found. Additionally, S-LANSS was associated with symptom duration and weight whereas PainDETECT was associated with sensitization-associated symptoms and anxiety levels, suggesting that the two questionnaires evaluate different aspects of the neuropathic pain spectrum in post-COVID pain patients.}, } @article {pmid35891354, year = {2022}, author = {Ward, B and Yombi, JC and Balligand, JL and Cani, PD and Collet, JF and de Greef, J and Dewulf, JP and Gatto, L and Haufroid, V and Jodogne, S and Kabamba, B and Pyr Dit Ruys, S and Vertommen, D and Elens, L and Belkhir, L}, title = {HYGIEIA: HYpothesizing the Genesis of Infectious Diseases and Epidemics through an Integrated Systems Biology Approach.}, journal = {Viruses}, volume = {14}, number = {7}, pages = {}, pmid = {35891354}, issn = {1999-4915}, mesh = {*COVID-19/complications/epidemiology ; *Communicable Diseases/epidemiology ; Humans ; Longitudinal Studies ; Metabolomics/methods ; Pandemics ; Systems Biology/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care.}, } @article {pmid35891317, year = {2022}, author = {Kaur, U and Bala, S and Joshi, A and Reddy, NTS and Japur, C and Chauhan, M and Pedapanga, N and Kumar, S and Mukherjee, A and Mishra, V and Talda, D and Singh, R and Gupta, RK and Yadav, AK and Rana, PJ and Srivastava, J and Bhat K, S and Singh, A and P G, NK and Pandey, M and Patwardhan, K and Kansal, S and Chakrabarti, SS}, title = {Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.}, journal = {Vaccines}, volume = {10}, number = {7}, pages = {}, pmid = {35891317}, issn = {2076-393X}, abstract = {Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.}, } @article {pmid35891272, year = {2022}, author = {Dattner, AM}, title = {Potential Immunologic and Integrative Methods to Enhance Vaccine Safety.}, journal = {Vaccines}, volume = {10}, number = {7}, pages = {}, pmid = {35891272}, issn = {2076-393X}, abstract = {Vaccine safety is measured by the disease protection it confers compared to the harm it may cause; both factors and their relative numbers have been the subject of disagreement. Cross-reactive attack of analogous self-antigens modified by dietary and microbiome factors is one of the poorly explored likely causes of harm. Screening for that and other risk factors might point out those most likely to develop severe vaccine reactions. Cooperation from those with opinions for and against vaccination in data gathering and vetting will lead to greater safety. Screening should include an integrative medical perspective regarding diet, microbiome, leaky gut, and other antigen sources. It might include emerging electronic technology or integrative energetic techniques vetted ultimately by cross-reactive lymphocyte testing or genetic evaluation. The knowledge gained from evaluating those with reactions could enhance the screening process and, since similar antigenic stimuli and reactions are involved, help long COVID sufferers. Centers for early identification and rescue from vaccine reactions could lower morbidity and mortality, and increase the percentage of people choosing to be vaccinated. Additional platforms for boosting; using lower dosage; other routes of administration, such as intranasal or intradermal needles; and possibly different antigens could make it easier to vaccinate globally to address the new variants of viruses rapidly arising.}, } @article {pmid35891179, year = {2022}, author = {Said, KB and Al-Otaibi, A and Aljaloud, L and Al-Anazi, B and Alsolami, A and Alreshidi, FS and On Behalf Of The Ha'il Com Research Unit Group, }, title = {The Frequency and Patterns of Post-COVID-19 Vaccination Syndrome Reveal Initially Mild and Potentially Immunocytopenic Signs in Primarily Young Saudi Women.}, journal = {Vaccines}, volume = {10}, number = {7}, pages = {}, pmid = {35891179}, issn = {2076-393X}, support = {RG20064//University of Hail/ ; }, abstract = {Vaccination is the most promising approach for ending or containing the SARS-CoV-2 pandemic. However, serious post-COVID-19 vaccine reactions, including immunocytopenia (ITP) syndrome, have been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of widely available specific therapeutics, vigilance is important while more studies are needed. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 vaccine side effects on febrile patients after administration three major vaccines. Results indicated that the majority of respondents administered Pfizer BioNtech vaccine (81%, n = 809); followed by AstraZeneca (16%, n = 155); and Moderna (3%, n = 34). Overall 998 participants, 74% (n = 737) showed no serious symptoms; however, 26.2% (n = 261) revealed typical syndromes. In a focused group of 722 participants, the following rates were identified: shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent among those who showed typical symptoms. The onset time was mostly between 1-3 days in 49% (n = 128), followed by 4-7 days in 21.8% (n = 57), 8-14 days in 16.5% (n = 43), and more than a month in 12.6% (n = 33). The onsets occurred mostly after the first, second, or both doses, 9%, 10%, and 7% of participants, respectively. The frequency of symptoms was significantly higher after Moderna[®] vaccine (p-value = 0.00006) and it was significantly lower in participants who received Pfizer (p-value = 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, sex, education, and nationality had no influence on the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID-19 vaccine syndrome.}, } @article {pmid35889971, year = {2022}, author = {Fernández-de-Las-Peñas, C and Cancela-Cilleruelo, I and Rodríguez-Jiménez, J and Gómez-Mayordomo, V and Pellicer-Valero, OJ and Martín-Guerrero, JD and Hernández-Barrera, V and Arendt-Nielsen, L and Torres-Macho, J}, title = {Associated-Onset Symptoms and Post-COVID-19 Symptoms in Hospitalized COVID-19 Survivors Infected with Wuhan, Alpha or Delta SARS-CoV-2 Variant.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {35889971}, issn = {2076-0817}, support = {LONG COVID EXP CM//Comunidad de Madrid/ ; }, abstract = {This study compared associated-symptoms at the acute phase of infection and post-COVID-19 symptoms between individuals hospitalized with the Wuhan, Alpha or Delta SARS-CoV-2 variant. Non-vaccinated individuals hospitalized because of SARS-CoV-2 infection in one hospital during three different waves of the pandemic (Wuhan, Alpha or Delta) were scheduled for a telephone interview. The presence of post-COVID-19 symptoms was systematically assessed. Hospitalization and clinical data were collected from medical records. A total of 201 patients infected with the Wuhan variant, 211 with the Alpha variant and 202 with Delta variant were assessed six months after hospitalization. Patients infected with the Wuhan variant had a greater number of symptoms at hospital admission (higher prevalence of fever, dyspnea or gastrointestinal problems) than those infected with Alpha or Delta variant (p < 0.01). A greater proportion of patients infected with the Delta variant reported headache, anosmia or ageusia as onset symptoms (p < 0.01). The mean number of post-COVID-19 symptoms was higher (p < 0.001) in individuals infected with the Wuhan variant (mean: 2.7 ± 1.3) than in those infected with the Alpha (mean: 1.8 ± 1.1) or Delta (mean: 2.1 ± 1.5) variant. Post-COVID-19 dyspnea was more prevalent (p < 0.001) in people infected with the Wuhan variant, whereas hair loss was higher in those infected with the Delta variant (p = 0.002). No differences in post-COVID-19 fatigue by SARS-CoV-2 variant were found (p = 0.594). Differences in COVID-19 associated onset symptoms and post-COVID-19 dyspnea were observed depending on the SARS-CoV-2 variant. The presence of fatigue was a common post-COVID-19 symptom to all SARS-CoV-2 variants.}, } @article {pmid35888568, year = {2022}, author = {Tokumasu, K and Honda, H and Sunada, N and Sakurada, Y and Matsuda, Y and Yamamoto, K and Nakano, Y and Hasegawa, T and Yamamoto, Y and Otsuka, Y and Hagiya, H and Kataoka, H and Ueda, K and Otsuka, F}, title = {Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {7}, pages = {}, pmid = {35888568}, issn = {1648-9144}, mesh = {*COVID-19/complications/epidemiology ; Canada ; *Fatigue Syndrome, Chronic/complications/diagnosis/epidemiology ; Female ; Headache ; Humans ; Male ; Retrospective Studies ; *Sleep Initiation and Maintenance Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.}, } @article {pmid35888154, year = {2022}, author = {Mumtaz, A and Sheikh, AAE and Khan, AM and Khalid, SN and Khan, J and Nasrullah, A and Sagheer, S and Sheikh, AB}, title = {COVID-19 Vaccine and Long COVID: A Scoping Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35888154}, issn = {2075-1729}, abstract = {As the COVID-19 pandemic progresses, changing definitions and therapeutics regarding the post-acute sequela of COVID-19, particularly long COVID, have become a subject of great interest and study. The study aims to describe the pathophysiology and discuss different therapeutic agents currently available for long COVID. Another objective is to assess comparative efficacy between different types of vaccines on symptoms of long COVID. A preliminary search was conducted using Ovid Medline, Embase, medRxiv, and NIH COVID-19 portfolios. A total of 16 studies were included in our review. Despite some of the data showing variable results, most of the vaccinated patients reported improvement in long COVID symptoms with no significant difference between various types of vaccines. Further trials are needed to better identify the comparative efficacy of vaccines for long COVID and ascertain other therapeutic modalities.}, } @article {pmid35886618, year = {2022}, author = {Su, Z and Cheshmehzangi, A and McDonnell, D and Ahmad, J and Šegalo, S and Xiang, YT and da Veiga, CP}, title = {The Advantages of the Zero-COVID-19 Strategy.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {14}, pages = {}, pmid = {35886618}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology/prevention & control ; COVID-19 Vaccines ; Humans ; Pandemics/prevention & control ; Public Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {Introduction: To curb the COVID-19 pandemic, countries across the globe have adopted either a mitigation or anelimination policy, such as the zero-COVID-19 strategy. However, further research is needed to systematically investigate the advantages of the zero-COVID-19 strategy in the literature. To bridge the research gap, this study examines the zero-COVID-19 strategy in terms of its advantages as a global anti-pandemic framework. Methods: A literature review was conducted in PubMed, PsycINFO, and Scopus to locate academic articles that discussed the advantages of the zero-COVID-19 strategy. Braun and Clarke's thematic analysis approach was adopted to guide the data analysis process. Results: The findings of our study show that the advantages of the zero-COVID-19 strategy range from short-term (e.g., limited virus infections, hospitalizations, and deaths), to medium-term (e.g., reduced presence of other infectious diseases), and long-term (e.g., low incidence of long COVID-19). While local residents mainly leverage these advantages, they also impact the global community (e.g., stable global supply of essentials, such as COVID-19 vaccines). Conclusions: COVID-19 is catastrophic, yet controllable. Our study examined the advantages of the zero-COVID-19 strategy from a nuanced perspective and discussed how these advantages benefit both the local and the global community in pandemic control and management. Future studies could investigate the shortcomings of the zero-COVID-19 strategy, especially its unintended consequences, such as adverse impacts on vulnerable populations' mental health, so that society could more efficiently, economically, and empathetically capitalize on the potential of the zero-COVID-19 strategy for the betterment of personal and public health.}, } @article {pmid35886491, year = {2022}, author = {Cárdaba-García, RM and Durantez-Fernández, C and Pérez, LP and Barba-Pérez, MÁ and Olea, E}, title = {What Do We Know Today about Long COVID? Nursing Care for a New Clinical Syndrome.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {14}, pages = {}, pmid = {35886491}, issn = {1660-4601}, mesh = {*COVID-19/complications/nursing ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent COVID, long COVID, long-effects, long-term effects or chronic COVID are all names of a new syndrome caused by a set of multi-organ symptoms that appear after having been infected with SARS-CoV-2 [...].}, } @article {pmid35883936, year = {2022}, author = {Di Chiara, C and Carraro, S and Zanconato, S and Cozzani, S and Baraldi, E and Giaquinto, C and Ferraro, VA and Donà, D}, title = {Preliminary Evidence on Pulmonary Function after Asymptomatic and Mild COVID-19 in Children.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35883936}, issn = {2227-9067}, support = {101016167//European Union's Horizon 2020/ ; }, abstract = {BACKGROUND: While it has been described that adults can develop long-lasting deterioration in pulmonary function (PF) after coronavirus disease 19 (COVID-19), regardless of disease severity, data on the long-term pneumological impact of SARS-CoV-2 infection in children are lacking.

METHODS: Performing a single-center, prospective, observational study on children aged 6-18 years with a previous diagnosis of asymptomatic/mild COVID-19, we evaluated the long-term impact of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children.

RESULTS: A total of 61 subjects underwent spirometry after a mean time of 10 ± 4 months from asymptomatic or mild infection. None of the children reported any respiratory symptoms, needed any inhaled therapy, or had abnormal lung function.

CONCLUSIONS: In our study, we observed that children and adolescents did not develop chronic respiratory symptoms and did not present lung function impairment after asymptomatic or mild SARS-CoV-2 infection.}, } @article {pmid35882253, year = {2022}, author = {Davies, F and Finlay, I and Howson, H and Rich, N}, title = {Recommendations for a voluntary Long COVID Registry.}, journal = {Journal of the Royal Society of Medicine}, volume = {115}, number = {8}, pages = {322-324}, pmid = {35882253}, issn = {1758-1095}, mesh = {*COVID-19/complications ; Humans ; Registries ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35881153, year = {2022}, author = {Elhiny, R and Al-Jumaili, AA and Yawuz, MJ}, title = {What might COVID-19 patients experience after recovery? A comprehensive review.}, journal = {The International journal of pharmacy practice}, volume = {30}, number = {5}, pages = {404-413}, pmid = {35881153}, issn = {2042-7174}, mesh = {Humans ; *COVID-19 ; Anxiety ; Vomiting ; *Gastrointestinal Diseases ; }, abstract = {OBJECTIVES: The objective of this review was to describe the COVID-19 complications after recovery.

METHODS: The researchers systematically reviewed studies that reported post-COVID-19 complications from three databases: PubMed, Google Scholar and the World Health Organization (WHO) COVID-19 database. The search was conducted between 21 November 2020 and 14 January 2021. Inclusion criteria were articles written in English, with primary data, reporting complications of COVID-19 after full recovery. The review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement.

KEY FINDINGS: This review included 69 studies with 146 725 patients from 22 countries related to post-COVID-19 complications. Thirty-six studies reported post-cure respiratory complications, ranging from dyspnoea to residual pulmonary fibrosis. Cardiac symptoms were reported in nine studies, including palpitation, chest pain and diastolic dysfunction. Neurological complications included post-traumatic stress syndrome, anxiety, depression, memory issues, insomnia and sleeping disturbance, cognitive impairments and stigma. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and acute liver injury. The physical decline was the most common symptom reported in the musculoskeletal complications.

CONCLUSION: COVID-19 may cause several types of complications after recovery (testing negative PCR). The identified complications include respiratory, neurological/mental, cardiovascular, gastrointestinal tract, urinary tract, musculoskeletal and miscellaneous complications. However, the key impairments were pulmonary consequences, psychological problems and exercise intolerance. Thus, COVID-19 patients may need long-term follow-up.}, } @article {pmid35879616, year = {2022}, author = {Subramanian, A and Nirantharakumar, K and Hughes, S and Myles, P and Williams, T and Gokhale, KM and Taverner, T and Chandan, JS and Brown, K and Simms-Williams, N and Shah, AD and Singh, M and Kidy, F and Okoth, K and Hotham, R and Bashir, N and Cockburn, N and Lee, SI and Turner, GM and Gkoutos, GV and Aiyegbusi, OL and McMullan, C and Denniston, AK and Sapey, E and Lord, JM and Wraith, DC and Leggett, E and Iles, C and Marshall, T and Price, MJ and Marwaha, S and Davies, EH and Jackson, LJ and Matthews, KL and Camaradou, J and Calvert, M and Haroon, S}, title = {Symptoms and risk factors for long COVID in non-hospitalized adults.}, journal = {Nature medicine}, volume = {28}, number = {8}, pages = {1706-1714}, pmid = {35879616}, issn = {1546-170X}, support = {COV-LT-0013/DH_/Department of Health/United Kingdom ; MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MR/P021220/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; NIHR203304/DH_/Department of Health/United Kingdom ; 300688/DH_/Department of Health/United Kingdom ; NIHR132914/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; Cohort Studies ; Ethnicity ; Female ; Humans ; Male ; Minority Groups ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.}, } @article {pmid35875995, year = {2022}, author = {Fogarty, H and Ward, SE and Townsend, L and Karampini, E and Elliott, S and Conlon, N and Dunne, J and Kiersey, R and Naughton, A and Gardiner, M and Byrne, M and Bergin, C and O'Sullivan, JM and Martin-Loeches, I and Nadarajan, P and Bannan, C and Mallon, PW and Curley, GF and Preston, RJS and Rehill, AM and Baker, RI and Cheallaigh, CN and O'Donnell, JS and , }, title = {Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {20}, number = {10}, pages = {2429-2438}, pmid = {35875995}, issn = {1538-7836}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {ADAMTS13 Protein ; Angiopoietin-2 ; *COVID-19/complications ; Convalescence ; *Hemostatics ; Humans ; Neovascularization, Pathologic ; Osteoprotegerin ; Platelet Factor 4 ; SARS-CoV-2 ; Thrombin ; von Willebrand Factor/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation.

PATIENTS AND METHODS: Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36).

RESULTS: ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively.

CONCLUSION: Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.}, } @article {pmid35875883, year = {2023}, author = {Gyöngyösi, M and Alcaide, P and Asselbergs, FW and Brundel, BJJM and Camici, GG and Martins, PDC and Ferdinandy, P and Fontana, M and Girao, H and Gnecchi, M and Gollmann-Tepeköylü, C and Kleinbongard, P and Krieg, T and Madonna, R and Paillard, M and Pantazis, A and Perrino, C and Pesce, M and Schiattarella, GG and Sluijter, JPG and Steffens, S and Tschöpe, C and Van Linthout, S and Davidson, SM}, title = {Long COVID and the cardiovascular system-elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases.}, journal = {Cardiovascular research}, volume = {119}, number = {2}, pages = {336-356}, pmid = {35875883}, issn = {1755-3245}, support = {725229/ERC_/European Research Council/International ; PG/16/85/32471/BHF_/British Heart Foundation/United Kingdom ; PG/19/51/34493/BHF_/British Heart Foundation/United Kingdom ; R01 HL144477/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; SARS-CoV-2 ; Heart ; *Heart Diseases ; Myocardium ; COVID-19 Testing ; }, abstract = {Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.}, } @article {pmid35874958, year = {2022}, author = {Koc, HC and Xiao, J and Liu, W and Li, Y and Chen, G}, title = {Long COVID and its Management.}, journal = {International journal of biological sciences}, volume = {18}, number = {12}, pages = {4768-4780}, pmid = {35874958}, issn = {1449-2288}, mesh = {*COVID-19/complications ; Health Personnel ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The pandemic of COVID-19 is the biggest public health crisis in 21[st] Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.}, } @article {pmid35874953, year = {2022}, author = {Park, JW and Wang, X and Xu, RH}, title = {Revealing the mystery of persistent smell loss in Long COVID patients.}, journal = {International journal of biological sciences}, volume = {18}, number = {12}, pages = {4795-4808}, pmid = {35874953}, issn = {1449-2288}, mesh = {*Anosmia/diagnosis/virology ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.}, } @article {pmid35874696, year = {2022}, author = {Noval Rivas, M and Porritt, RA and Cheng, MH and Bahar, I and Arditi, M}, title = {Multisystem Inflammatory Syndrome in Children and Long COVID: The SARS-CoV-2 Viral Superantigen Hypothesis.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {941009}, pmid = {35874696}, issn = {1664-3224}, support = {P41 GM103712/GM/NIGMS NIH HHS/United States ; R01 AI072726/AI/NIAID NIH HHS/United States ; R01 GM139297/GM/NIGMS NIH HHS/United States ; R01 HL139766/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Child ; *Connective Tissue Diseases ; Humans ; Neurotoxins ; RNA, Viral ; SARS-CoV-2 ; Superantigens ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Multisystem inflammatory syndrome in children (MIS-C) is a febrile pediatric inflammatory disease that may develop weeks after initial SARS-CoV-2 infection or exposure. MIS-C involves systemic hyperinflammation and multiorgan involvement, including severe cardiovascular, gastrointestinal (GI) and neurological symptoms. Some clinical attributes of MIS-C-such as persistent fever, rashes, conjunctivitis and oral mucosa changes (red fissured lips and strawberry tongue)-overlap with features of Kawasaki disease (KD). In addition, MIS-C shares striking clinical similarities with toxic shock syndrome (TSS), which is triggered by bacterial superantigens (SAgs). The remarkable similarities between MIS-C and TSS prompted a search for SAg-like structures in the SARS-CoV-2 virus and the discovery of a unique SAg-like motif highly similar to a Staphylococcal enterotoxin B (SEB) fragment in the SARS-CoV-2 spike 1 (S1) glycoprotein. Computational studies suggest that the SAg-like motif has a high affinity for binding T-cell receptors (TCRs) and MHC Class II proteins. Immunosequencing of peripheral blood samples from MIS-C patients revealed a profound expansion of TCR β variable gene 11-2 (TRBV11-2), which correlates with MIS-C severity and serum cytokine levels, consistent with a SAg-triggered immune response. Computational sequence analysis of SARS-CoV-2 spike further identified conserved neurotoxin-like motifs which may alter neuronal cell function and contribute to neurological symptoms in COVID-19 and MIS-C patients. Additionally, autoantibodies are detected during MIS-C, which may indicate development of post-SARS-CoV-2 autoreactive and autoimmune responses. Finally, prolonged persistence of SARS-CoV-2 RNA in the gut, increased gut permeability and elevated levels of circulating S1 have been observed in children with MIS-C. Accordingly, we hypothesize that continuous and prolonged exposure to the viral SAg-like and neurotoxin-like motifs in SARS-CoV-2 spike may promote autoimmunity leading to the development of post-acute COVID-19 syndromes, including MIS-C and long COVID, as well as the neurological complications resulting from SARS-CoV-2 infection.}, } @article {pmid35874528, year = {2022}, author = {Beaudry, RI and Brotto, AR and Varughese, RA and de Waal, S and Fuhr, DP and Damant, RW and Ferrara, G and Lam, GY and Smith, MP and Stickland, MK}, title = {Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {917886}, pmid = {35874528}, issn = {1664-042X}, abstract = {Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.}, } @article {pmid35873350, year = {2022}, author = {Chen, AK and Wang, X and McCluskey, LP and Morgan, JC and Switzer, JA and Mehta, R and Tingen, M and Su, S and Harris, RA and Hess, DC and Rutkowski, EK}, title = {Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA.}, journal = {Brain, behavior, & immunity - health}, volume = {24}, number = {}, pages = {100491}, pmid = {35873350}, issn = {2666-3546}, support = {R01 NS112511/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection.

METHODS: The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis.

RESULTS: Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing.

CONCLUSION: Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.}, } @article {pmid35871259, year = {2022}, author = {Fernández-de-Las-Peñas, C and Rodríguez-Jiménez, J and Moro-López-Menchero, P and Cancela-Cilleruelo, I and Pardo-Hernández, A and Hernández-Barrera, V and Gil-de-Miguel, Á}, title = {Psychometric properties of the Spanish version of the EuroQol-5D-5L in previously hospitalized COVID-19 survivors with long COVID.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {12605}, pmid = {35871259}, issn = {2045-2322}, mesh = {*COVID-19/complications ; Humans ; Psychometrics/methods ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The EuroQol 5-dimensions 5-levels (EQ-5D-5L) is a generic patient-reported outcome measures (PROM) used for evaluating health-related quality of life (HRQoL). No data on its psychometric properties in COVID-19 survivors is available. We aimed to describe internal consistency, test-retest reliability, and construct validity of the EQ-5D-5L in people with long-COVID. Ninety-three (n = 93) individuals previously hospitalized due to COVID-19 with post-COVID symptoms completed the EQ-5D-5L questionnaire twice one year after hospital discharge in a three-week interval. Internal consistency (Cronbach alpha and Omega value), test-retest reliability (kappa and ICC2,1) and construct validity (factor analysis), and floor/ceiling effects were calculated. No ceiling effect was observed in any dimension whereas the floor effect ranged from 53.76 to 94.62%. The overall Cronbach's α value was 0.75 (95%CI 0.64-0.83) and the Omega ω value was 0.77 (95%CI 0.66-0.84), showing good internal consistency of the questionnaire. Further, Cronbach's alpha values the of each dimension ranged from 0.63 to 0.77 whereas those for Omega values ranged from 0.70 to 0.79. The test-retest reliability of the total score was excellent (ICC2,1 0.86, 95%CI 0.798-0.911). The agreement percentage ranged from 85.13 to 96.77%; but kappa coefficients ranged from fair (κ: 0.37) to good (κ: 0.61). The factor analysis showed factor loadings from 0.585 to 0.813 supporting good construct validity. The EQ-5D-5L has good psychometric properties to be used as a PROM to assess HRQoL in hospitalized COVID-19 survivors with long-COVID.}, } @article {pmid35868675, year = {2022}, author = {Lauria, A and Carfì, A and Benvenuto, F and Bramato, G and Ciciarello, F and Rocchi, S and Rota, E and Salerno, A and Stella, L and Tritto, M and Di Paola, A and Pais, C and Tosato, M and Janiri, D and Sani, G and Pagano, FC and Fantoni, M and Bernabei, R and Landi, F and Bizzarro, A and , }, title = {Neuropsychological Measures of Long COVID-19 Fog in Older Subjects.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {593-603}, pmid = {35868675}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Humans ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 is known to impact older people more severely and to cause persistent symptoms during the recovery phase, including cognitive and neurologic ones. We investigated the cognitive and neurologic features of 100 elderly patients with confirmed diagnosis of coronavirus disease 2019 evaluated in the postacute phase through a direct neuropsychological evaluation consisting on Mini Mental State Examination and 8 neuropsychological tests. Overall, a total of 33 participants were found to perform at a level considered to be pathologic; more specifically, 33%, 23%, and 20% failed on Trial Making, Digit Span Backwards, and Frontal Evaluation Battery tests, respectively.}, } @article {pmid35868674, year = {2022}, author = {Tosato, M and Ciciarello, F and Zazzara, MB and Pais, C and Savera, G and Picca, A and Galluzzo, V and Coelho-Júnior, HJ and Calvani, R and Marzetti, E and Landi, F and , }, title = {Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {565-591}, pmid = {35868674}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Dietary Supplements ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The persistence of COVID-19 symptoms weeks or months after an initial SARS-CoV-2 infection has become one of the most burdensome legacies of the pandemic. This condition, known as long COVID syndrome, affects many persons of all age groups and is associated with substantial reductions of quality of life. Several mechanisms may be involved in long COVID syndrome, including chronic inflammation, metabolic perturbations, endothelial dysfunction, and gut dysbiosis. These pathogenic mechanisms overlap with those of the aging process and may aggravate pre-existing degenerative conditions. This review discusses bioactive foods, supplements, and nutraceuticals as possible interventions against long COVID syndrome.}, } @article {pmid35868673, year = {2022}, author = {Grund, S and Bauer, JM}, title = {Malnutrition and Sarcopenia in COVID-19 Survivors.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {559-564}, pmid = {35868673}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications/epidemiology ; Geriatric Assessment/methods ; Humans ; *Malnutrition/diagnosis/epidemiology/etiology ; Nursing Homes ; Nutrition Assessment ; Nutritional Status ; *Sarcopenia/diagnosis/epidemiology/etiology ; Survivors ; }, abstract = {Malnutrition has been one of the most common complications of older COVID-19 survivors. COVID-19 associated symptoms like loss of appetite as well as changes in taste and smell may trigger the deterioration of nutritional status, while other complications of the disease may contribute to it, like respiratory failure that necessitates admission to the ICU. Especially in nursing home residents reduced food intake may be related to preexisting and also to incident geriatric syndromes like delirium. Sarcopenia has also been highly prevalent in older COVID-19 survivors. It is caused and exacerbated by COVID-19-associated inflammatory processes, total or partial immobilization, and malnutrition. COVID-19 survivors may be at high risk of developing the vicious circle that results from the interaction of deteriorating nutritional status and declining functionality. Regular monitoring of nutritional and functional status is, therefore, indicated in all older COVID-19 survivors. If malnutrition and/or functional decline have been identified in this patient population, low-threshold provision of individualized nutritional and exercise interventions should be installed. In those that are most seriously affected by malnutrition and sarcopenia ambulatory or inpatient rehabilitation has to be considered. Geriatric rehabilitation programs should be specifically adapted to the needs of older patients with COVID-19.}, } @article {pmid35868672, year = {2022}, author = {Montes-Ibarra, M and Oliveira, CLP and Orsso, CE and Landi, F and Marzetti, E and Prado, CM}, title = {The Impact of Long COVID-19 on Muscle Health.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {545-557}, pmid = {35868672}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Humans ; *Muscle Strength/physiology ; Muscle, Skeletal ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 negatively impacts several organs and systems weeks or months after initial diagnosis. Skeletal muscle can be affected, leading to fatigue, lower mobility, weakness, and poor physical performance. Older adults are at increased risk of developing musculoskeletal symptoms during long COVID. Systemic inflammation, physical inactivity, and poor nutritional status are some of the mechanisms leading to muscle dysfunction in individuals with long COVID. Current evidence suggests that long COVID negatively impacts body composition, muscle function, and quality of life. Muscle mass and function assessments can contribute toward the identification, diagnosis, and management of poor muscle health resulting from long COVID.}, } @article {pmid35868671, year = {2022}, author = {Rodriguez-Sanchez, I and Rodriguez-Mañas, L and Laosa, O}, title = {Long COVID-19: The Need for an Interdisciplinary Approach.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {533-544}, pmid = {35868671}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications ; Frail Elderly ; *Frailty ; Humans ; *Sarcopenia/etiology/prevention & control ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long coronavirus disease 2019 (COVID-19) is characterized by persistent COVID-19 symptoms that last for at least 2 months. In the elderly population, apart from the typical symptoms (fatigue, cough, or dyspnea), unspecific symptoms coexist (functional deterioration, cognitive impairment, or delirium) that can mitigate the prevalence of this syndrome in this age group. Its main consequence is the functional decline, leading to sarcopenia, frailty, and disability, in addition to the nutritional and cognitive disorders. Thus, a multicomponent and individualized program (exercise, diet, cognitive stimulation) should be designed for older people with persistent COVID, where new technologies could be useful.}, } @article {pmid35868667, year = {2022}, author = {Zazzara, MB and Bellieni, A and Calvani, R and Coelho-Junior, HJ and Picca, A and Marzetti, E}, title = {Inflammaging at the Time of COVID-19.}, journal = {Clinics in geriatric medicine}, volume = {38}, number = {3}, pages = {473-481}, pmid = {35868667}, issn = {1879-8853}, mesh = {Aged ; *COVID-19/complications/therapy ; Cytokines ; Humans ; Inflammation/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe coronavirus disease 2019 (COVID-19) is associated with overproduction of proinflammatory cytokines. The ensuing cytokine storm contributes to the development of severe pneumonia and, possibly, to long-term symptom persistence (long COVID). The chronic state of low-grade inflammation that accompanies aging (inflammaging) might predispose older adults to severe COVID-19. Inflammaging may also contribute to symptom persistence following acute COVID-19. Antiinflammatory drugs and immunomodulatory agents can achieve significant therapeutic gain during acute COVID-19. Lifestyle interventions (eg, physical activity, diet) may be proposed as strategies to counteract inflammation and mitigate long-term symptom persistence.}, } @article {pmid35868478, year = {2022}, author = {Izzo, R and Trimarco, V and Mone, P and Aloè, T and Capra Marzani, M and Diana, A and Fazio, G and Mallardo, M and Maniscalco, M and Marazzi, G and Messina, N and Mininni, S and Mussi, C and Pelaia, G and Pennisi, A and Santus, P and Scarpelli, F and Tursi, F and Zanforlin, A and Santulli, G and Trimarco, B}, title = {Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.}, journal = {Pharmacological research}, volume = {183}, number = {}, pages = {106360}, pmid = {35868478}, issn = {1096-1186}, mesh = {Arginine/therapeutic use ; *Ascorbic Acid/therapeutic use ; *COVID-19/complications ; Humans ; Vitamins ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms.

METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment).

RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm.

CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.}, } @article {pmid35868344, year = {2022}, author = {Wais, T and Hasan, M and Rai, V and Agrawal, DK}, title = {Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics.}, journal = {Expert review of clinical immunology}, volume = {18}, number = {9}, pages = {947-960}, pmid = {35868344}, issn = {1744-8409}, support = {R01 HL144125/HL/NHLBI NIH HHS/United States ; R01 HL147662/HL/NHLBI NIH HHS/United States ; }, mesh = {Biomarkers ; Brain ; *Brain-Gut Axis ; *COVID-19/complications ; *Gastrointestinal Diseases ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Infection with COVID-19 results in acute respiratory symptoms followed by long COVID multi-organ effects presenting with neurological, cardiovascular, musculoskeletal, and gastrointestinal (GI) manifestations. Temporal relationship between gastrointestinal and neurological symptoms is unclear but warranted for exploring better clinical care for COVID-19 patients.

AREAS COVERED: We critically reviewed the temporal relationship between gut-brain axis after SARS-CoV-2 infection and the molecular mechanisms involved in neuroinvasion following GI infection. Mediators are identified that could serve as biomarkers and therapeutic targets in SARS-CoV-2. We discussed the potential therapeutic approaches to mitigate the effects of GI infection with SARS-CoV-2.

EXPERT OPINION: Altered gut microbiota cause increased expression of various mediators, including zonulin causing disruption of tight junction. This stimulates enteric nervous system and signals to CNS precipitating neurological sequalae. Published reports suggest potential role of cytokines, immune cells, B(0)AT1 (SLC6A19), ACE2, TMRSS2, TMPRSS4, IFN-γ, IL-17A, zonulin, and altered gut microbiome in gut-brain axis and associated neurological sequalae. Targeting these mediators and gut microbiome to improve immunity will be of therapeutic significance. In-depth research and well-designed large-scale population-based clinical trials with multidisciplinary and collaborative approaches are warranted. Investigating the temporal relationship between organs involved in long-term sequalae is critical due to evolving variants of SARS-CoV-2.}, } @article {pmid35867593, year = {2022}, author = {Omar, IM and Weaver, JS and Samet, JD and Serhal, AM and Mar, WA and Taljanovic, MS}, title = {Musculoskeletal Manifestations of COVID-19: Currently Described Clinical Symptoms and Multimodality Imaging Findings.}, journal = {Radiographics : a review publication of the Radiological Society of North America, Inc}, volume = {42}, number = {5}, pages = {1415-1432}, pmid = {35867593}, issn = {1527-1323}, mesh = {*COVID-19/complications ; Humans ; Multimodal Imaging ; *Musculoskeletal System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19, the clinical syndrome produced by infection with SARS-CoV-2, can result in multisystem organ dysfunction, including respiratory failure and hypercoagulability, which can lead to critical illness and death. Musculoskeletal (MSK) manifestations of COVID-19 are common but have been relatively underreported, possibly because of the severity of manifestations in other organ systems. Additionally, patients who have undergone sedation and who are critically ill are often unable to alert clinicians of their MSK symptoms. Furthermore, some therapeutic measures such as medications and vaccinations can worsen existing MSK symptoms or cause additional symptoms. Symptoms may persist or occur months after the initial infection, known as post-COVID condition or long COVID. As the global experience with COVID-19 and the vaccination effort increases, certain patterns of MSK disease involving the bones, muscles, peripheral nerves, blood vessels, and joints have emerged, many of which are likely related to a hyperinflammatory host response, prothrombotic state, or therapeutic efforts rather than direct viral toxicity. Imaging findings for various COVID-19-related MSK pathologic conditions across a variety of modalities are being recognized, which can be helpful for diagnosis, treatment guidance, and follow-up. The online slide presentation from the RSNA Annual Meeting is available for this article. [©]RSNA, 2022.}, } @article {pmid35866369, year = {2022}, author = {Pandori, WJ and Padgett, LE and Alimadadi, A and Gutierrez, NA and Araujo, DJ and Huh, CJ and Olingy, CE and Dinh, HQ and Wu, R and Vijayanand, P and Chee, SJ and Ottensmeier, CH and Hedrick, CC}, title = {Single-cell immune profiling reveals long-term changes in myeloid cells and identifies a novel subset of CD9[+] monocytes associated with COVID-19 hospitalization.}, journal = {Journal of leukocyte biology}, volume = {112}, number = {5}, pages = {1053-1063}, pmid = {35866369}, issn = {1938-3673}, support = {F32 HL146069/HL/NHLBI NIH HHS/United States ; P01 HL136275/HL/NHLBI NIH HHS/United States ; S10 OD018499/OD/NIH HHS/United States ; T32 AI125179/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *COVID-19 ; Monocytes ; SARS-CoV-2 ; Interleukin-8/metabolism ; Lipopolysaccharides/metabolism ; Myeloid Cells ; Hospitalization ; Tetraspanin 29/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in severe immune dysfunction, hospitalization, and death. Many patients also develop long-COVID-19, experiencing symptoms months after infection. Although significant progress has been made in understanding the immune response to acute SARS-CoV-2 infection, gaps remain in our knowledge of how innate immunity influences disease kinetics and severity. We hypothesized that cytometry by time-of-flight analysis of PBMCs from healthy and infected subjects would identify novel cell surface markers and innate immune cell subsets associated with COVID-19 severity. In this pursuit, we identified monocyte and dendritic cell subsets that changed in frequency during acute SARS-CoV-2 infection and correlated with clinical parameters of disease severity. Subsets of nonclassical monocytes decreased in frequency in hospitalized subjects, yet increased in the most severe patients and positively correlated with clinical values associated with worse disease severity. CD9, CD163, PDL1, and PDL2 expression significantly increased in hospitalized subjects, and CD9 and 6-Sulfo LacNac emerged as the markers that best distinguished monocyte subsets amongst all subjects. CD9[+] monocytes remained elevated, whereas nonclassical monocytes remained decreased, in the blood of hospitalized subjects at 3-4 months postinfection. Finally, we found that CD9[+] monocytes functionally released more IL-8 and MCP-1 after LPS stimulation. This study identifies new monocyte subsets present in the blood of COVID-19 patients that correlate with disease severity, and links CD9[+] monocytes to COVID-19 progression.}, } @article {pmid35863367, year = {2022}, author = {Lawton, T and Alwan, NA}, title = {The UK COVID-19 Inquiry must examine the foundations of pandemic decision making.}, journal = {Lancet (London, England)}, volume = {400}, number = {10358}, pages = {1087-1089}, pmid = {35863367}, issn = {1474-547X}, mesh = {*COVID-19 ; Decision Making ; Humans ; *Pandemics/prevention & control ; SARS-CoV-2 ; United Kingdom/epidemiology ; }, } @article {pmid35862724, year = {2022}, author = {Bassett, M and Salemi, M and Rife Magalis, B}, title = {Lessons Learned and Yet-to-Be Learned on the Importance of RNA Structure in SARS-CoV-2 Replication.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {86}, number = {3}, pages = {e0005721}, pmid = {35862724}, issn = {1098-5557}, mesh = {*COVID-19 ; Humans ; Pandemics ; RNA ; *SARS-CoV-2/genetics ; }, abstract = {SARS-CoV-2, the etiological agent responsible for the COVID-19 pandemic, is a member of the virus family Coronaviridae, known for relatively extensive (~30-kb) RNA genomes that not only encode for numerous proteins but are also capable of forming elaborate structures. As highlighted in this review, these structures perform critical functions in various steps of the viral life cycle, ultimately impacting pathogenesis and transmissibility. We examine these elements in the context of coronavirus evolutionary history and future directions for curbing the spread of SARS-CoV-2 and other potential human coronaviruses. While we focus on structures supported by a variety of biochemical, biophysical, and/or computational methods, we also touch here on recent evidence for novel structures in both protein-coding and noncoding regions of the genome, including an assessment of the potential role for RNA structure in the controversial finding of SARS-CoV-2 integration in "long COVID" patients. This review aims to serve as a consolidation of previous works on coronavirus and more recent investigation of SARS-CoV-2, emphasizing the need for improved understanding of the role of RNA structure in the evolution and adaptation of these human viruses.}, } @article {pmid35862681, year = {2022}, author = {Oishi, K and Horiuchi, S and Minkoff, JM and tenOever, BR}, title = {The Host Response to Influenza A Virus Interferes with SARS-CoV-2 Replication during Coinfection.}, journal = {Journal of virology}, volume = {96}, number = {15}, pages = {e0076522}, pmid = {35862681}, issn = {1098-5514}, mesh = {Animals ; *COVID-19/immunology/mortality/virology ; *Coinfection/immunology/virology ; *Cross-Priming/immunology ; Humans ; *Influenza A Virus, H1N1 Subtype/immunology ; *Influenza, Human/immunology/virology ; Interferons/immunology ; Mesocricetus/immunology/virology ; *SARS-CoV-2/growth & development/immunology ; *Virus Replication/immunology ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) represent two highly transmissible airborne pathogens with pandemic capabilities. Although these viruses belong to separate virus families-SARS-CoV-2 is a member of the family Coronaviridae, while IAV is a member of the family Orthomyxoviridae-both have shown zoonotic potential, with significant animal reservoirs in species in close contact with humans. The two viruses are similar in their capacity to infect human airways, and coinfections resulting in significant morbidity and mortality have been documented. Here, we investigate the interaction between SARS-CoV-2 USA-WA1/2020 and influenza H1N1 A/California/04/2009 virus during coinfection. Competition assays in vitro were performed in susceptible cells that were either interferon type I/III (IFN-I/-III) nonresponsive or IFN-I/-III responsive, in addition to an in vivo golden hamster model. We find that SARS-CoV-2 infection does not interfere with IAV biology in vivo, regardless of timing between the infections. In contrast, we observe a significant loss of SARS-CoV-2 replication following IAV infection. The latter phenotype correlates with increased levels of IFN-I/-III and immune priming that interferes with the kinetics of SARS-CoV-2 replication. Together, these data suggest that cocirculation of SARS-CoV-2 and IAV is unlikely to result in increased severity of disease. IMPORTANCE The human population now has two circulating respiratory RNA viruses with high pandemic potential, namely, SARS-CoV-2 and influenza A virus. As both viruses infect the airways and can result in significant morbidity and mortality, it is imperative that we also understand the consequences of getting coinfected. Here, we demonstrate that the host response to influenza A virus uniquely interferes with SARS-CoV-2 biology although the inverse relationship is not evident. Overall, we find that the host response to both viruses is comparable to that to SARS-CoV-2 infection alone.}, } @article {pmid35861926, year = {2022}, author = {Graham, EL and Koralnik, IJ and Liotta, EM}, title = {Therapeutic Approaches to the Neurologic Manifestations of COVID-19.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {19}, number = {5}, pages = {1435-1466}, pmid = {35861926}, issn = {1878-7479}, mesh = {Adult ; Humans ; *COVID-19/complications ; SARS-CoV-2 ; Quality of Life ; *Stroke ; Seizures ; }, abstract = {As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.}, } @article {pmid35861678, year = {2022}, author = {Mayor, N and Meza-Torres, B and Okusi, C and Delanerolle, G and Chapman, M and Wang, W and Anand, S and Feher, M and Macartney, J and Byford, R and Joy, M and Gatenby, P and Curcin, V and Greenhalgh, T and Delaney, B and de Lusignan, S}, title = {Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.}, journal = {JMIR public health and surveillance}, volume = {8}, number = {8}, pages = {e36989}, pmid = {35861678}, issn = {2369-2960}, support = {25310/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*COVID-19/complications ; COVID-19 Testing ; Humans ; Phenotype ; Primary Health Care ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition.

OBJECTIVE: This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not.

METHODS: We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression.

RESULTS: The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19.

CONCLUSIONS: Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.}, } @article {pmid35860936, year = {2022}, author = {Takao, M and Ohira, M}, title = {[Outpatient Clinic for Long COVID].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {74}, number = {7}, pages = {885-891}, doi = {10.11477/mf.1416202143}, pmid = {35860936}, issn = {1881-6096}, mesh = {Ambulatory Care Facilities ; *COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {We summarize the current status of outpatient clinics for patients with long-term coronavirus disease 2019-associated post-acute sequelae severe acute respiratory syndrome coronavirus 2 infection (PASC) at the National Center of Neurology and Psychiatry Hospital. The pathogenesis of PASC is not well understood and its symptoms vary. Recently, the number of patients with PASC has been increasing, meaning that many physicians will need to treat such patients occasionally. Although diagnostic, testing, and treatment methods have not been established, clinicians must apply a long-term management approach to patients based on the clinical evaluation of each individual. Furthermore, there is an urgent need to establish a system for analyzing PASC on a long-term basis.}, } @article {pmid35860935, year = {2022}, author = {Watanabe, H and Shima, S and Mizutani, Y and Ueda, A and Ito, M}, title = {[Long COVID: Pathogenesis and Therapeutic Approach].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {74}, number = {7}, pages = {879-884}, doi = {10.11477/mf.1416202142}, pmid = {35860935}, issn = {1881-6096}, mesh = {*COVID-19/complications ; Cytokines ; Humans ; Inflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {A group of patients with coronavirus disease 2019 (COVID-19) exhibited various persistent or new systemic symptoms, including psychiatric symptoms, sleep disturbances, exercise intolerance, arthralgia, headache, cognitive decline, brain fog, and autonomic symptoms, all of which persisted long after the resolution of infectious symptoms. Several imaging studies have shown that long COVID cases present with decreased glucose metabolism and progressive brain atrophy. Although no single pathological hypothesis thoroughly explains the varied clinical presentations and timings, the following have attracted attention: 1) persistent viral infection, 2) persistent inflammation, 3) involvement of the autoimmune system, and 4) mitochondrial dysfunction. In all these hypotheses, inflammatory cytokines may be involved in orthostatic dysregulation by decreasing the expression and activity of ACE2, consequently changing the blood pressure through vagus nerve hyperactivation. Myopathy and peripheral neuropathy may also be caused by direct infection of the muscles and nerves, hypoxia, mitochondrial damage, and cytokine storm. Furthermore, multiple theories regarding the mechanisms by which systemic inflammatory findings affect the central nervous system have been postulated, including neuroinflammation caused by inflammatory cells crossing the blood-brain barrier via choroid plexus cells and the involvement of various autoantibodies. Despite these findings, no definitive consensus has been reached due to the complexity and diversity of COVID-19 pathophysiology. Thus, it is essential to understand the neurological symptoms and pathophysiology involved in long COVID.}, } @article {pmid35858254, year = {2022}, author = {Groenveld, T and Achttien, R and Smits, M and de Vries, M and van Heerde, R and Staal, B and van Goor, H and , }, title = {Feasibility of Virtual Reality Exercises at Home for Post-COVID-19 Condition: Cohort Study.}, journal = {JMIR rehabilitation and assistive technologies}, volume = {9}, number = {3}, pages = {e36836}, pmid = {35858254}, issn = {2369-2529}, abstract = {BACKGROUND: Between 30% to 76% of COVID-19 patients have persistent physical and mental symptoms, sometimes up to 9 months after acute COVID-19. Current rehabilitation is mostly focused on the physical symptoms, whereas experts have agreed on the need for a biopsychosocial approach. A novel approach such as virtual reality (VR) rehabilitation at home might benefit patients and therapists, especially considering the expected rush of patients with post-COVID-19 condition needing rehabilitation.

OBJECTIVE: The aim of this study was to investigate the feasibility of self-administered VR exercises at home for post-COVID-19 condition.

METHODS: This was a single-arm feasibility study in an outpatient care setting. Patients who needed physiotherapy because of post-COVID-19 condition were included as determined by the treating physiotherapist. Participants performed VR physical exercises at home for a period of 6 weeks and were allowed to perform VR mental exercise through applications available on the VR platform to reduce stress and anxiety and promote cognitive functioning. The main outcomes were related to feasibility (ie, duration and frequency of VR use), safety (ie, adverse events), patient satisfaction, and reasons to withdraw. Physical performance, daily activities, cognitive functioning, anxiety and depression, and the quality of life were measured before and after.

RESULTS: In total, 48 patients were included; 1 (2%) patient did not start VR, and 7 (15%) patients withdrew, mostly due to dizziness. Almost 70% (33/47) of participants reported experiencing any adverse event during VR exercising. However, only 25% (9/36) recalled these events at the end of the intervention period. The majority (27/36, 75%) of the patients described VR as having a positive influence on their recovery, and the global satisfaction score was 67%. The average VR use was 30 minutes per session, 3-4 times a week for 3-6 weeks. The overall use of VR applications was almost equally distributed over the 3 sets of VR exercises (physical, relaxing, and cognitive). However, the use frequency of physical exercises seemed to decrease over time, whereas the use of cognitive and relaxation exercises remained stable. Physical performance and quality of life outcomes were significantly improved after 6 weeks.

CONCLUSIONS: VR physical exercises at home is feasible and safe with good acceptance in a significant percentage of patient with post-COVID-19 condition.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04505761; https://clinicaltrials.gov/ct2/show/NCT04505761.}, } @article {pmid35857629, year = {2022}, author = {Frere, JJ and Serafini, RA and Pryce, KD and Zazhytska, M and Oishi, K and Golynker, I and Panis, M and Zimering, J and Horiuchi, S and Hoagland, DA and Møller, R and Ruiz, A and Kodra, A and Overdevest, JB and Canoll, PD and Borczuk, AC and Chandar, V and Bram, Y and Schwartz, R and Lomvardas, S and Zachariou, V and tenOever, BR}, title = {SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery.}, journal = {Science translational medicine}, volume = {14}, number = {664}, pages = {eabq3059}, pmid = {35857629}, issn = {1946-6242}, support = {K23 DC019678/DC/NIDCD NIH HHS/United States ; P01 DA047233/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/complications ; Cricetinae ; Humans ; Interferons ; Mesocricetus ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster after either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely affected the olfactory bulb (OB) and olfactory epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month after viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.}, } @article {pmid35857581, year = {2022}, author = {Narasimhan, H and Wu, Y and Goplen, NP and Sun, J}, title = {Immune determinants of chronic sequelae after respiratory viral infection.}, journal = {Science immunology}, volume = {7}, number = {73}, pages = {eabm7996}, doi = {10.1126/sciimmunol.abm7996}, pmid = {35857581}, issn = {2470-9468}, mesh = {*COVID-19/complications/immunology ; Coronavirus ; Humans ; Pandemics ; *Respiratory Tract Infections/immunology/virology ; *Virus Diseases/complications/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The acute effects of various respiratory viral infections have been well studied, with extensive characterization of the clinical presentation as well as viral pathogenesis and host responses. However, over the course of the recent COVID-19 pandemic, the incidence and prevalence of chronic sequelae after acute viral infections have become increasingly appreciated as a serious health concern. Post-acute sequelae of COVID-19, alternatively described as "long COVID-19," are characterized by symptoms that persist for longer than 28 days after recovery from acute illness. Although there exists substantial heterogeneity in the nature of the observed sequelae, this phenomenon has also been observed in the context of other respiratory viral infections including influenza virus, respiratory syncytial virus, rhinovirus, severe acute respiratory syndrome coronavirus, and Middle Eastern respiratory syndrome coronavirus. In this Review, we discuss the various sequelae observed following important human respiratory viral pathogens and our current understanding of the immunological mechanisms underlying the failure of restoration of homeostasis in the lung.}, } @article {pmid35857271, year = {2022}, author = {di Filippo, L and Frara, S and Doga, M and Giustina, A}, title = {The osteo-metabolic phenotype of COVID-19: an update.}, journal = {Endocrine}, volume = {78}, number = {2}, pages = {247-254}, pmid = {35857271}, issn = {1559-0100}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; COVID-19 Vaccines ; Parathyroid Hormone ; Phenotype ; Post-Acute COVID-19 Syndrome ; }, abstract = {CONTEXT: In the multifaceted COVID-19 clinical scenario characterized by a multi-system disorder with negative implications not only on respiratory function but also on cardiac, hematological, neurological and endocrine-metabolic systems, a distinctive osteo-metabolic phenotype with an independent influence on disease severity and recovery of patients affected was early reported.

AIM: To summarize and update the main evidences regarding the distinct components of this phenotype in acute and Long COVID-19, reinforcing its clinical relevance and discussing the main pathophysiological and clinical-therapeutic implications of the most recent reported findings.

RESULTS: This emerging phenotype is characterized by a widespread acute hypocalcemia and hypovitaminosis D with an impaired compensatory parathyroid hormone response, and a high prevalence of skeletal complications such as vertebral fractures. The clinical relevance of this osteo-metabolic phenotype on acute COVID-19 is well characterized, and novel seminal evidences are progressively highlighting its importance also in predicting patient's long-term outcomes and Long COVID-19 occurrence.

CONCLUSIONS: These findings reinforced the central role of a multidisciplinary team, including endocrinologists, in evaluating these patients for a proactive search of each aspect of the osteo-metabolic phenotype components since they may represent suitable therapeutic targets to prevent SARS-CoV-2 infection, poor COVID-19 outcomes, Long COVID-19 occurrence and even possibly better responses to COVID-19 vaccination.}, } @article {pmid35856065, year = {2022}, author = {Wang, SY and Adejumo, P and See, C and Onuma, OK and Miller, EJ and Spatz, ES}, title = {Characteristics of patients referred to a cardiovascular disease clinic for post-acute sequelae of SARS-CoV-2 infection.}, journal = {American heart journal plus : cardiology research and practice}, volume = {18}, number = {}, pages = {100176}, pmid = {35856065}, issn = {2666-6022}, support = {U54 MD010711/MD/NIMHD NIH HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; R01 EB028106/EB/NIBIB NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; T32 GM136651/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: There is limited literature on cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC).

METHODS: This observational study aimed to describe the characteristics, diagnostic evaluations, and new cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC, and to identify factors associated with cardiovascular symptoms with no identifiable cardiac pathology.

RESULTS: Of 126 patients, average age was 46 years, and 34 % were male. Patients presented on average five months after COVID-19 diagnosis. The most common symptoms were dyspnea (52 %), chest pain/pressure (48 %), palpitations (44 %), and fatigue (42 %), commonly associated with exertion or exercise intolerance. New cardiovascular diseases were present in 23 % of cases. The remainder exhibited common symptoms which we termed "cardiovascular PASC syndrome."

DISCUSSION: We found that only one in four patients had a new cardiovascular diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.}, } @article {pmid35854691, year = {2022}, author = {Compagno, S and Palermi, S and Pescatore, V and Brugin, E and Sarto, M and Marin, R and Calzavara, V and Nizzetto, M and Scevola, M and Aloi, A and Biffi, A and Zanella, C and Carretta, G and Gallo, S and Giada, F}, title = {Physical and psychological reconditioning in long COVID syndrome: Results of an out-of-hospital exercise and psychological - based rehabilitation program.}, journal = {International journal of cardiology. Heart & vasculature}, volume = {41}, number = {}, pages = {101080}, pmid = {35854691}, issn = {2352-9067}, abstract = {BACKGROUND: Long Covid Syndrome (LCS) is used to describe signs and symptoms that continue or develop after acute COVID-19 infection. Natural history and treatment of this syndrome are still poorly understood, even if evidences suggest the potential role of physical rehabilitation in improving symptoms in these patients.

AIM OF THE STUDY: The aim of the present study was to evaluate effectiveness, safety and feasibility of an out-of-hospital multidisciplinary rehabilitation (MDR) program, based both on physical and psychological reconditioning, in reducing symptoms and improving physical fitness and psychological parameters in patients with LCS.

METHODS: Thirty consecutive patients with LCS (18 males, mean age 58 years) underwent an accurate medical screening process including anthropometric and muscular strength evaluation, cardiopulmonary exercise test, quality of life (QoL) and psychological appraisal before and after a MDR program.

RESULTS: At baseline, all LCS patients were strongly symptomatic and showed severe impairments in physical performance, QoL and psychological parameters. No adverse effects and dropouts were observed during the exercise training sessions. After the MDR program, COVID-19 residual symptoms significantly decreased, and significant improvements in upper and lower limb muscular strength, cardiopulmonary parameters, perceived physical and mental health, depression and anxiety were observed.

CONCLUSIONS: The present study confirms the severe physical and psychological impairment of patients with LCS and suggests that a MDR program is effective, safe and feasible in these patients and could promote their physical and psychological recovery.}, } @article {pmid35853751, year = {2022}, author = {Hachinski, V}, title = {The New Brain Age.}, journal = {Neurology}, volume = {99}, number = {11}, pages = {468-472}, doi = {10.1212/WNL.0000000000201059}, pmid = {35853751}, issn = {1526-632X}, mesh = {Artificial Intelligence ; Brain/diagnostic imaging ; *COVID-19/complications ; Humans ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {The pandemic is transforming neurology. Long COVID will linger, neurologic diseases will increase, and technology, artificial intelligence, and new virtual worlds will usher a new age of the brain and new roles for neurologists. The pandemic has compelled international collaboration, greatly increased communications, and accelerated drug and vaccines approvals. It also dramatized the close interconnection of cognitive, mental, and social health and their relevance to building back better health, education, work, and leisure. Brain health is the key to health, productivity, and well-being. Neurologists are best placed to lead brain knowledge integration and application through the unifying theme of brain health by becoming advocates, healers, and guardians of the brain.}, } @article {pmid35853689, year = {2022}, author = {Hunt, J}, title = {Making space for disability studies within a structurally competent medical curriculum: reflections on long Covid.}, journal = {Medical humanities}, volume = {}, number = {}, pages = {}, doi = {10.1136/medhum-2022-012415}, pmid = {35853689}, issn = {1473-4265}, abstract = {While critically informed approaches to medical education are increasingly advocated in literature, discussion of the potential role of disability studies in informing pedagogy and practice is largely lacking. The emergence of long Covid, alongside the strong possibility of a wave of covid-related disability, underlines an urgent need for medicine to develop more contextualised, nuanced and structurally competent understandings of chronic illness and disability. This article argues that the integration of thinking from disability studies into medical curricula offers a pathway to such understanding, informing a more equitable, holistic and patient-centred approach to practice. Further, a structurally competent, antiableist approach positions clinicians and patients as allies, working together within a structural context that constrains both parties. Such positioning may mitigate tensions within the clinical encounter, tensions that are well documented in the realm of marginalised chronic illness and disability. While the possibilities arising from a partnership between disability studies and medicine are numerous, the foci here are the social relational model of disability and the concept of psycho-emotional disablism, within a broader framework of critical disability studies. It is argued that inadequate healthcare provision and policy in the realm of long Covid can be understood as a form of structural and psycho-emotional disablism, arising from and reinforcing an ableist psychosocial imaginary permeated with neoliberal assumptions, and carrying a risk of furthering both disability and impairment. After considering long Covid through these particular lenses, the article concludes with a discussion of how a partnership between disability studies and a structurally competent approach to medical education might translate into practice.}, } @article {pmid35853576, year = {2022}, author = {Ormiston, CK and Świątkiewicz, I and Taub, PR}, title = {Postural orthostatic tachycardia syndrome as a sequela of COVID-19.}, journal = {Heart rhythm}, volume = {19}, number = {11}, pages = {1880-1889}, pmid = {35853576}, issn = {1556-3871}, support = {R01 DK118278/DK/NIDDK NIH HHS/United States ; R01 HL136407/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology/therapy ; *Orthostatic Intolerance/epidemiology ; Pandemics ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; Tachycardia ; }, abstract = {Postural orthostatic tachycardia syndrome (POTS) is a complex multisystem disorder characterized by orthostatic intolerance and tachycardia and may be triggered by viral infection. Recent reports indicate that 2%-14% of coronavirus disease 2019 (COVID-19) survivors develop POTS and 9%-61% experience POTS-like symptoms, such as tachycardia, orthostatic intolerance, fatigue, and cognitive impairment within 6-8 months of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Pathophysiological mechanisms of post-COVID-19 POTS are not well understood. Current hypotheses include autoimmunity related to SARS-CoV-2 infection, autonomic dysfunction, direct toxic injury by SARS-CoV-2 to the autonomic nervous system, and invasion of the central nervous system by SARS-CoV-2. Practitioners should actively assess POTS in patients with post-acute COVID-19 syndrome symptoms. Given that the symptoms of post-COVID-19 POTS are predominantly chronic orthostatic tachycardia, lifestyle modifications in combination with the use of heart rate-lowering medications along with other pharmacotherapies should be considered. For example, ivabradine or β-blockers in combination with compression stockings and increasing salt and fluid intake has shown potential. Treatment teams should be multidisciplinary, including physicians of various specialties, nurses, psychologists, and physiotherapists. Additionally, more resources to adequately care for this patient population are urgently needed given the increased demand for autonomic specialists and clinics since the start of the COVID-19 pandemic. Considering our limited understanding of post-COVID-19 POTS, further research on topics such as its natural history, pathophysiological mechanisms, and ideal treatment is warranted. This review evaluates the current literature available on the associations between COVID-19 and POTS, possible mechanisms, patient assessment, treatments, and future directions to improving our understanding of post-COVID-19 POTS.}, } @article {pmid35853464, year = {2022}, author = {Bechmann, N and Maccio, U and Kotb, R and Dweik, RA and Cherfane, M and Moch, H and Bornstein, SR and Varga, Z}, title = {COVID-19 Infections in Gonads: Consequences on Fertility?.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {549-555}, pmid = {35853464}, issn = {1439-4286}, mesh = {Aged ; *COVID-19/complications ; COVID-19 Vaccines ; Female ; Fertility ; Gonads ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pandemics ; Pituitary-Adrenal System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 may influence human fertility and sexuality in several ways. Different cell types in gonads show a constitutive expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), which provide potential entry pathways for SARS-CoV-2. In addition to the biological effects of a COVID-19 infection on the gonads, the impact of the ongoing COVID-19 pandemic on mental health issues and sexual behavior may affect reproduction. This review summarizes the current knowledge on the influence of COVID-19 on the gonads and discusses possible consequences on human fertility. In this context, the close interaction between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis in response to COVID-19-related stress is discussed. Some women noticed changes in their menstrual cycle during the COVID-19 pandemic, which could be due to psychological stress, for example. In addition, occasional cases of reduced oocyte quality and ovarian function are described after COVID-19 infection. In men, COVID-19 may cause a short-term decrease in fertility by damaging testicular tissue and/or impairing spermatogenesis. Moreover, decreased ratio testosterone/LH and FSH/LH in COVID-19 compared to aged-matched healthy men has been reported. Available data do not suggest any effect of the available SARS-CoV-2 vaccines on fertility. The effects of long COVID on human fertility have been reported and include cases with premature ovarian failure and oligomenorrhoea in women and erectile dysfunction in men. Despite the increasing knowledge about the effects of COVID-19 infections on human gonads and fertility, the long-term consequences of the COVID-19 pandemic cannot yet be assessed in this context.}, } @article {pmid35853019, year = {2022}, author = {Rezel-Potts, E and Douiri, A and Sun, X and Chowienczyk, PJ and Shah, AM and Gulliford, MC}, title = {Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK.}, journal = {PLoS medicine}, volume = {19}, number = {7}, pages = {e1004052}, pmid = {35853019}, issn = {1549-1676}, support = {CH/1999001/11735/BHF_/British Heart Foundation/United Kingdom ; RE/18/2/34213/BHF_/British Heart Foundation/United Kingdom ; SP/14/8/31352/BHF_/British Heart Foundation/United Kingdom ; IS-BRC-1215-20006/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; *Cardiovascular Diseases/epidemiology/etiology ; Cohort Studies ; *Diabetes Mellitus/epidemiology ; Humans ; *Pulmonary Embolism ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Acute Coronavirus Disease 2019 (COVID-19) has been associated with new-onset cardiovascular disease (CVD) and diabetes mellitus (DM), but it is not known whether COVID-19 has long-term impacts on cardiometabolic outcomes. This study aimed to determine whether the incidence of new DM and CVDs are increased over 12 months after COVID-19 compared with matched controls.

METHODS AND FINDINGS: We conducted a cohort study from 2020 to 2021 analysing electronic records for 1,356 United Kingdom family practices with a population of 13.4 million. Participants were 428,650 COVID-19 patients without DM or CVD who were individually matched with 428,650 control patients on age, sex, and family practice and followed up to January 2022. Outcomes were incidence of DM and CVD. A difference-in-difference analysis estimated the net effect of COVID-19 allowing for baseline differences, age, ethnicity, smoking, body mass index (BMI), systolic blood pressure, Charlson score, index month, and matched set. Follow-up time was divided into 4 weeks from index date ("acute COVID-19"), 5 to 12 weeks from index date ("post-acute COVID-19"), and 13 to 52 weeks from index date ("long COVID-19"). Net incidence of DM increased in the first 4 weeks after COVID-19 (adjusted rate ratio, RR 1.81, 95% confidence interval (CI) 1.51 to 2.19) and remained elevated from 5 to 12 weeks (RR 1.27, 1.11 to 1.46) but not from 13 to 52 weeks overall (1.07, 0.99 to 1.16). Acute COVID-19 was associated with net increased CVD incidence (5.82, 4.82 to 7.03) including pulmonary embolism (RR 11.51, 7.07 to 18.73), atrial arrythmias (6.44, 4.17 to 9.96), and venous thromboses (5.43, 3.27 to 9.01). CVD incidence declined from 5 to 12 weeks (RR 1.49, 1.28 to 1.73) and showed a net decrease from 13 to 52 weeks (0.80, 0.73 to 0.88). The analyses were based on health records data and participants' exposure and outcome status might have been misclassified.

CONCLUSIONS: In this study, we found that CVD was increased early after COVID-19 mainly from pulmonary embolism, atrial arrhythmias, and venous thromboses. DM incidence remained elevated for at least 12 weeks following COVID-19 before declining. People without preexisting CVD or DM who suffer from COVID-19 do not appear to have a long-term increase in incidence of these conditions.}, } @article {pmid35852546, year = {2022}, author = {Lehmann, HC}, title = {[Neuromuscular manifestations in long-COVID syndrome].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {761-768}, pmid = {35852546}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The term long-COVID syndrome encompasses symptoms that occur after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, persisting over a period of several weeks, and which cannot be explained by another diagnosis. Long-COVID is considered to be a multiorgan condition. In this review article, the data regarding neuromuscular manifestations of long-COVID syndrome are summarized and evaluated based on criteria, such as effect size, plausibility, coherence, and experimental evidence. So far, myalgia and autonomic dysfunction (especially postural tachycardia syndrome) have been postulated as neuromuscular symptoms of long-COVID; however, the evidence to date is limited. In addition to very heterogeneous methodologies and different definitions of long-COVID in the clinical studies, conclusive experimental data supporting the described symptoms as a specific long-term consequence of COVID-19 are lacking.}, } @article {pmid35851732, year = {2022}, author = {Asadi-Pooya, AA and Nemati, M and Nemati, H}, title = {'Long COVID': Symptom persistence in children hospitalised for COVID-19.}, journal = {Journal of paediatrics and child health}, volume = {58}, number = {10}, pages = {1836-1840}, pmid = {35851732}, issn = {1440-1754}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Fatigue/etiology ; Follow-Up Studies ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIM: We aimed to describe the long-term outcome with respect to symptom persistence amongst children hospitalised for COVID-19.

METHODS: This was a follow-up study of 58 children and adolescents hospitalised with COVID-19. For all patients, the data were collected in a phone call to the family in December 2021 (9 months after the initial study and more than 13 months after their admission to hospital). We inquired about their current health status and obtained information, if the responding parent consented orally to participate and answer the questions.

RESULTS: Fifty-one children and adolescents were studied. Only five patients (10%) had persistent symptoms compatible with long-COVID; the reported symptoms include fatigue in four (8%), weakness in three (6%), exercise intolerance in two (4%) and shortness of breath in two (4%) patients. Four patients (7.8%), who did not have any symptoms of long-COVID in phase 1 of the study, reported new-onset symptoms or complaints that are potentially compatible with the diagnosis of long-COVID (weakness, myalgia, excess sputum, cough, fatigue) in the current phase.

CONCLUSIONS: Symptom persistence of long-COVID is infrequent amongst children hospitalised for COVID-19. Most of the symptoms of long-COVID will resolve with the passage of time and the residual symptoms are often mild and tolerable. The scientific community should carefully and clearly define long-COVID and its natural course in order to facilitate and harmonise future studies.}, } @article {pmid35851024, year = {2022}, author = {Zhang, MR and Huang, HG and Chen, HX and Deng, YF}, title = {Factors associated with poor mental health outcomes in nurses in COVID-19-designated hospitals in the postepidemic period in Guangdong Province: a cross-sectional study.}, journal = {BMJ open}, volume = {12}, number = {7}, pages = {e061116}, pmid = {35851024}, issn = {2044-6055}, mesh = {Anxiety/epidemiology/psychology ; *COVID-19/complications/epidemiology ; China/epidemiology ; Cross-Sectional Studies ; Depression/epidemiology ; Hospitals ; Humans ; Outcome Assessment, Health Care ; Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The early days of the COVID-19 pandemic placed enormous pressure and subsequent negative psychological problems on nurses, but at this stage of the year-long COVID-19 outbreak, the level of stress and negative emotions that nurses experience is unclear. Our study attempted to assess the factors influencing mental health status in nurses during the postepidemic period of COVID-19.

DESIGN: Cross-sectional study.

SETTING: COVID-19 designated hospitals.

PARTICIPANTS: 1284 Chinese nurses.

MAIN OUTCOME MEASURES: Electronic questionnaires, including the Chinese version of the Perceived Stress Scale (CPSS) and Symptom Checklist-90 (SCL-90), were distributed for self-evaluation. Regression analysis was used to analyse the associated factors of psychological stress among variables such as age, years of nursing experience, weekly working hours, anxiety symptoms, somatisation symptoms and compulsive symptoms.

RESULTS: A total of 1284 respondents from COVID-19-designated hospitals in Guangdong Province were studied. The average CPSS score for all respondents was 22.91±7.12. A total of 38.5% of respondents scored ≥26 on the CPSS, indicating a significant degree of psychological stress. Nurses with high psychological stress had higher levels of anxiety symptoms (41.7% vs 8.0%), somatisation symptoms (31.4% vs 7.7%) and compulsion symptoms (62.3% vs 27.0%) than nurses with low psychological stress. Stepwise multiple linear regression revealed that weekly working hours, years of nursing experience, anxiety symptoms, somatisation symptoms and compulsion symptoms had a linear relationship with the participants' psychological stress scores.

CONCLUSION: Nurses experienced significant physical and psychological risk while working in the postepidemic period. Our findings suggest that nurses still need support to protect their physical and mental health.}, } @article {pmid35850558, year = {2022}, author = {Gerlis, C and Barradell, A and Gardiner, NY and Chaplin, E and Goddard, A and Singh, SJ and Daynes, E}, title = {The Recovery Journey and the Rehabilitation Boat - A qualitative study to explore experiences of COVID-19 rehabilitation.}, journal = {Chronic respiratory disease}, volume = {19}, number = {}, pages = {14799731221114266}, pmid = {35850558}, issn = {1479-9731}, mesh = {*COVID-19 ; Dyspnea/etiology ; Exercise ; Focus Groups ; Humans ; Qualitative Research ; }, abstract = {INTRODUCTION: There are early data to suggest that a rehabilitation programme can help with on-going symptoms of COVID-19, including breathlessness, exercise limitation and fatigue. As yet, there are no published data to understand patients' perceived acceptability of a rehabilitation programme for COVID-19.

METHODS: 2 focus groups (n = 9) and 4 one to one interviews were conducted with participants who attended a rehabilitation program following COVID-19. Interviews were analysed using reflexive thematic analysis with an inductive approach.

RESULTS: Two overarching themes were generated from the data. The first, The Recovery Journey is sub-divided into five sub-themes of Expectations, Individual and Varied Journeys, Mental and Physical Improvements, Self-values and The Journey Continues. The second overarching theme, The Rehabilitation boat contains five subthemes: Programme Delivery, Safe and Supportive, Validation and Assurance, Shared Reflections and Education.

CONCLUSION: A rehabilitation programme for post COVID-19 symptoms was considered to be acceptable and viewed positively in terms of improving physical and mental symptoms. The opportunity to share the experience with others in the same boat was highly valued in the context of an unexpected and potentially lonely COVID-19 recovery.}, } @article {pmid35849572, year = {2022}, author = {Robertson, JL and Senger, RS and Talty, J and Du, P and Sayed-Issa, A and Avellar, ML and Ngo, LT and Gomez De La Espriella, M and Fazili, TN and Jackson-Akers, JY and Guruli, G and Orlando, G}, title = {Alterations in the molecular composition of COVID-19 patient urine, detected using Raman spectroscopic/computational analysis.}, journal = {PloS one}, volume = {17}, number = {7}, pages = {e0270914}, pmid = {35849572}, issn = {1932-6203}, mesh = {*COVID-19/complications/diagnosis ; Humans ; SARS-CoV-2 ; Spectrum Analysis, Raman/methods ; Urinalysis/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {We developed and tested a method to detect COVID-19 disease, using urine specimens. The technology is based on Raman spectroscopy and computational analysis. It does not detect SARS-CoV-2 virus or viral components, but rather a urine 'molecular fingerprint', representing systemic metabolic, inflammatory, and immunologic reactions to infection. We analyzed voided urine specimens from 46 symptomatic COVID-19 patients with positive real time-polymerase chain reaction (RT-PCR) tests for infection or household contact with test-positive patients. We compared their urine Raman spectra with urine Raman spectra from healthy individuals (n = 185), peritoneal dialysis patients (n = 20), and patients with active bladder cancer (n = 17), collected between 2016-2018 (i.e., pre-COVID-19). We also compared all urine Raman spectra with urine specimens collected from healthy, fully vaccinated volunteers (n = 19) from July to September 2021. Disease severity (primarily respiratory) ranged among mild (n = 25), moderate (n = 14), and severe (n = 7). Seventy percent of patients sought evaluation within 14 days of onset. One severely affected patient was hospitalized, the remainder being managed with home/ambulatory care. Twenty patients had clinical pathology profiling. Seven of 20 patients had mildly elevated serum creatinine values (>0.9 mg/dl; range 0.9-1.34 mg/dl) and 6/7 of these patients also had estimated glomerular filtration rates (eGFR) <90 mL/min/1.73m2 (range 59-84 mL/min/1.73m2). We could not determine if any of these patients had antecedent clinical pathology abnormalities. Our technology (Raman Chemometric Urinalysis-Rametrix®) had an overall prediction accuracy of 97.6% for detecting complex, multimolecular fingerprints in urine associated with COVID-19 disease. The sensitivity of this model for detecting COVID-19 was 90.9%. The specificity was 98.8%, the positive predictive value was 93.0%, and the negative predictive value was 98.4%. In assessing severity, the method showed to be accurate in identifying symptoms as mild, moderate, or severe (random chance = 33%) based on the urine multimolecular fingerprint. Finally, a fingerprint of 'Long COVID-19' symptoms (defined as lasting longer than 30 days) was located in urine. Our methods were able to locate the presence of this fingerprint with 70.0% sensitivity and 98.7% specificity in leave-one-out cross-validation analysis. Further validation testing will include sampling more patients, examining correlations of disease severity and/or duration, and employing metabolomic analysis (Gas Chromatography-Mass Spectrometry [GC-MS], High Performance Liquid Chromatography [HPLC]) to identify individual components contributing to COVID-19 molecular fingerprints.}, } @article {pmid35848380, year = {2022}, author = {Shanthanna, H and Nelson, AM and Kissoon, N and Narouze, S}, title = {The COVID-19 pandemic and its consequences for chronic pain: a narrative review.}, journal = {Anaesthesia}, volume = {77}, number = {9}, pages = {1039-1050}, pmid = {35848380}, issn = {1365-2044}, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; *Chronic Pain/etiology/therapy ; Headache ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic transformed everyday life, but the implications were most impactful for vulnerable populations, including patients with chronic pain. Moreover, persistent pain is increasingly recognised as a key manifestation of long COVID. This narrative review explores the consequences of the COVID-19 pandemic for chronic pain. Publications were identified related to the COVID-19 pandemic influence on the burden of chronic pain, development of new-onset pain because of long COVID with proposed mechanisms and COVID-19 vaccines and pain interventions. Broadly, mechanisms underlying pain due to SARS-CoV-2 infection could be caused by 'systemic inflammatory-immune mechanisms', 'direct neuropathic mechanisms' or 'secondary mechanisms due to the viral infection or treatment'. Existing chronic pain populations were variably impacted and social determinants of health appeared to influence the degree of effect. SARS-CoV-2 infection increased the absolute numbers of patients with pain and headache. In the acute phase, headache as a presenting symptom predicted a milder course. New-onset chronic pain was reportedly common and likely involves multiple mechanisms; however, its prevalence decreases over time and symptoms appear to fluctuate. Patients requiring intensive support were particularly susceptible to long COVID symptoms. Some evidence suggests steroid exposure (often used for pain interventions) may affect vaccine efficacy, but there is no evidence of clinical repercussions to date. Although existing chronic pain management could help with symptomatic relief, there is a need to advance research focusing on mechanism-based treatments within the domain of multidisciplinary care.}, } @article {pmid35847821, year = {2022}, author = {Vernon, SD and Funk, S and Bateman, L and Stoddard, GJ and Hammer, S and Sullivan, K and Bell, J and Abbaszadeh, S and Lipkin, WI and Komaroff, AL}, title = {Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {917019}, pmid = {35847821}, issn = {2296-858X}, support = {U54 AI138370/AI/NIAID NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment ("brain fog"), orthostatic intolerance (OI) and other symptoms ("Long COVID"). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

METHODS: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

PARTICIPANTS: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

RESULTS: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

CONCLUSIONS: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.}, } @article {pmid35847457, year = {2022}, author = {Colas, C and Bayle, M and Labeix, P and Botelho-Nevers, E and Gagneux-Brunon, A and Cazorla, C and Schein, F and Breugnon, E and Garcin, A and Feasson, L and Roche, F and Hupin, D}, title = {Management of Long COVID-The CoviMouv' Pilot Study: Importance of Adapted Physical Activity for Prolonged Symptoms Following SARS-CoV2 Infection.}, journal = {Frontiers in sports and active living}, volume = {4}, number = {}, pages = {877188}, pmid = {35847457}, issn = {2624-9367}, abstract = {CONTEXT: After a COVID-19 infection, some patients have persistent symptoms, the most common is fatigue. To prevent it from becoming chronic (post-COVID-19 syndrome), early management before 3 months could be useful. Exercise and education are recommended.

OBJECTIVE: To assess fatigue in patients with prolonged symptoms after COVID-19 infection and who received a mixed program of remote adapted physical activity and therapeutic education. The secondary objective was to evaluate the efficacy and safety of this training method thanks to aerobic and anaerobic parameters.

METHODS: "CoviMouv': From Coaching in Visual to Mouv in real" is a nonrandomized controlled pilot study. Patients in telerehabilitation followed 12 remote exercise sessions and 3 therapeutic education workshops. Patients on traditional rehabilitation followed their program with a community-based physiotherapist.

RESULTS: Fatigue was reduced after the one-month intervention in both groups (p = 0.010). The majority of aerobic parameters were significantly improved, e.g., maximal oxygen uptake (p = 0.005), walking distance (p = 0.019) or hyperventilation values (p = 0.035). The anaerobic parameter was not improved (p = 0.400). No adverse event was declared.

DISCUSSION: Telerehabilitation is a good alternative when a face-to-face program is not possible. This care at an early stage of the disease could help prevent the chronicity of post-COVID-19 symptoms and the installation of vicious circles of physical deconditioning. A larger study would be necessary.}, } @article {pmid35846757, year = {2022}, author = {Queiroz, MAF and Neves, PFMD and Lima, SS and Lopes, JDC and Torres, MKDS and Vallinoto, IMVC and Bichara, CDA and Dos Santos, EF and de Brito, MTFM and da Silva, ALS and Leite, MM and da Costa, FP and Viana, MNDSA and Rodrigues, FBB and de Sarges, KML and Cantanhede, MHD and da Silva, R and Bichara, CNC and van den Berg, AVS and Veríssimo, AOL and Carvalho, MDS and Henriques, DF and Dos Santos, CP and Nunes, JAL and Costa, IB and Viana, GMR and Carneiro, FRO and Palacios, VRDCM and Quaresma, JAS and Brasil-Costa, I and Dos Santos, EJM and Falcão, LFM and Vallinoto, ACR}, title = {Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {922422}, pmid = {35846757}, issn = {2235-2988}, mesh = {Biomarkers ; *COVID-19/complications ; Cytokines ; Humans ; Interleukin-10 ; Interleukin-17 ; Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Middle Aged ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.}, } @article {pmid35844548, year = {2022}, author = {Colarusso, C and Terlizzi, M and Maglio, A and Molino, A and Candia, C and Vitale, C and Hansbro, PM and Vatrella, A and Pinto, A and Sorrentino, R}, title = {Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {934264}, pmid = {35844548}, issn = {1664-3224}, mesh = {*COVID-19/blood/immunology/pathology ; Carrier Proteins ; Caspase 1/immunology ; *DNA-Binding Proteins/blood/immunology ; Humans ; Inflammasomes/blood/immunology ; Interferon-alpha/metabolism ; Leukocytes, Mononuclear/immunology ; *Pulmonary Fibrosis/blood/immunology/pathology/virology ; SARS-CoV-2 ; Transforming Growth Factor beta/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-β. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-β were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.}, } @article {pmid35844354, year = {2022}, author = {Awoyemi, T and Ebili, U and Olusanya, A and Ogunniyi, KE and Adejumo, AV}, title = {Twitter Sentiment Analysis of Long COVID Syndrome.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e25901}, pmid = {35844354}, issn = {2168-8184}, abstract = {Background Long COVID syndrome originated as a patient phrased terminology which was initially used to describe a group of vague symptoms that persisted after recovering from COVID-19. However, it has moved from a patient lingo to a recognized pathological entity which refers to a group of symptoms that lasts weeks or months after the COVID-19 illness. The novelty of this condition, the inadequacy of research on long COVID syndrome, and its origin as a patient-coined terminology necessitated exploring the disease's sentiments and conversations by analyzing publicly available tweets. Method Tweets were extracted using the Twarc2 tool for tweets in the English language with the keywords (long COVID syndrome, long COVID, post-COVID syndrome, post-acute sequelae of SARS-CoV-2, long-term COVID, long haulers, and chronic COVID syndrome) between March 25, 2022, and April 1, 2022. The analyses included frequency of the keywords, sentiment analysis, and topic modeling to identify and explore discussion topics over time. A natural language approach and the latent Dirichlet allocation algorithm were used to determine the most shared tweet topics, categorize clusters, and identify themes based on keyword analysis. Results The search yielded 62,232 tweets. The tweets were reduced to 10,670 tweets after removing the duplicates. The vast majority of the tweets originated from the United States of America (38%), United Kingdom (30%), and Canada (13%), with the most common hashtags being #longcovid (36%) and #covid (6.36%), and the most frequently used word being people (1.05%). The top three emotions detected by our analysis were trust (11.68%), fear (11.26%), and sadness (9.76%). The sentiment analysis results showed that people have comparable levels of positivity (19.90%) and negativity (18.39%) towards long COVID. Conclusions Our analysis revealed comparable sentiments about long COVID syndrome, albeit slightly positive. Most tweets connoted trust (positive), fear (negative), and sadness (negative). These emotions were linked with concerns about the infection, pandemic, chronic disability, and governmental policies. We believe this study would be important in guiding information dissemination and governmental policy implementation necessary in tackling long COVID syndrome.}, } @article {pmid35844318, year = {2022}, author = {Shivani, F and Kumari, N and Bai, P and Rakesh, F and Haseeb, M and Kumar, S and Jamil, A and Zaidi, M and Shaukat, F and Rizwan, A}, title = {Long-Term Symptoms of COVID-19: One-Year Follow-Up Study.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e25937}, pmid = {35844318}, issn = {2168-8184}, abstract = {INTRODUCTION: Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome.

METHODS: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States).

RESULTS: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%).

CONCLUSION: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals' attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.}, } @article {pmid35843984, year = {2022}, author = {Franke, C and Berlit, P and Prüss, H}, title = {Neurological manifestations of post-COVID-19 syndrome S1-guideline of the German society of neurology.}, journal = {Neurological research and practice}, volume = {4}, number = {1}, pages = {28}, pmid = {35843984}, issn = {2524-3489}, abstract = {Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to COVID-19 (COrona VIrus Disease-2019). SARS-CoV-2 acute infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. Neurological manifestations are commonly reported during the post-acute phase and are also present in Long-COVID (LCS) and post-COVID-19 syndrome (PCS). In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of COVID-19. In December 2021 this S1 guideline was revised and guidance for the care of patients with post-COVID-19 syndrome regarding neurological manifestations was added. This is an abbreviated version of the post-COVID-19 syndrome chapter of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).}, } @article {pmid35843340, year = {2023}, author = {Shih, AR and Misdraji, J}, title = {COVID-19: gastrointestinal and hepatobiliary manifestations.}, journal = {Human pathology}, volume = {132}, number = {}, pages = {39-55}, pmid = {35843340}, issn = {1532-8392}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Gastrointestinal Diseases/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Tract ; }, abstract = {SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.}, } @article {pmid35841032, year = {2022}, author = {Spiesshoefer, J and Friedrich, J and Regmi, B and Geppert, J and Jörn, B and Kersten, A and Giannoni, A and Boentert, M and Marx, G and Marx, N and Daher, A and Dreher, M}, title = {Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.}, journal = {Respiratory research}, volume = {23}, number = {1}, pages = {187}, pmid = {35841032}, issn = {1465-993X}, mesh = {Aftercare ; *COVID-19/complications ; Case-Control Studies ; Diaphragm/diagnostic imaging ; Dyspnea/diagnosis/etiology ; Humans ; Patient Discharge ; Physical Exertion ; Respiration, Artificial ; *Respiratory Distress Syndrome/diagnosis/etiology/therapy ; SARS-CoV-2 ; }, abstract = {Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.}, } @article {pmid35840817, year = {2022}, author = {Verger, A and Barthel, H and Tolboom, N and Fraioli, F and Cecchin, D and Albert, NL and van Berckel, B and Boellaard, R and Brendel, M and Ekmekcioglu, O and Semah, F and Traub-Weidinger, T and van de Weehaeghe, D and Morbelli, S and Guedj, E}, title = {2-[[18]F]-FDG PET for imaging brain involvement in patients with long COVID: perspective of the EANM Neuroimaging Committee.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {49}, number = {11}, pages = {3599-3606}, pmid = {35840817}, issn = {1619-7089}, mesh = {Brain/diagnostic imaging ; *COVID-19/complications ; *Fluorodeoxyglucose F18 ; Humans ; Neuroimaging ; Positron-Emission Tomography/methods ; Radiopharmaceuticals ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35840463, year = {2022}, author = {Jolobe, OMP}, title = {Post-COVID-19 diabetes in the context of long COVID.}, journal = {The American journal of emergency medicine}, volume = {61}, number = {}, pages = {208-209}, pmid = {35840463}, issn = {1532-8171}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Diabetes Mellitus/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35839175, year = {2022}, author = {Cocciolillo, F and Di Giuda, D and Morello, R and De Rose, C and Valentini, P and Buonsenso, D}, title = {Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience.}, journal = {The Pediatric infectious disease journal}, volume = {41}, number = {8}, pages = {663-665}, pmid = {35839175}, issn = {1532-0987}, mesh = {Brain ; *COVID-19/complications/diagnostic imaging ; Child ; Fluorodeoxyglucose F18 ; Frontal Lobe/diagnostic imaging ; Humans ; Positron-Emission Tomography/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.}, } @article {pmid35838974, year = {2022}, author = {Turton, N and Heaton, RA and Hargreaves, IP}, title = {COVID-19 and the Assessment of Coenzyme Q10.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2511}, number = {}, pages = {355-365}, pmid = {35838974}, issn = {1940-6029}, mesh = {*COVID-19/complications/diagnosis ; Humans ; Mitochondrial Diseases ; *Ubiquinone/analogs & derivatives/chemistry/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coenzyme Q10 (CoQ10) plays an essential electron carrier role in the mitochondrial electron transfer chain (ETC) as well as being a potent antioxidant and influencing inflammatory mediators. In view of these functions, the reason why certain individuals may be more susceptible to the severe disease or long-term complications (long COVID) of COVID-19 infection may be associated with an underlying deficit in cellular CoQ10 status. Thus, our group has outlined an analytical method for the determination of cellular CoQ10 status using HPLC linked UV detection at 275 nm. This method has been utilized in patient tissue samples to investigate evidence of a CoQ10 deficiency and thus may have potential in determining the possible susceptibility of individuals to severe disease associated with COVID-19 infection or to long COVID.}, } @article {pmid35838670, year = {2022}, author = {Schneiderman, M and Rumain, B and Kaganovskiy, L and Geliebter, A}, title = {Incidence and Relative Risk of COVID-19 in Adolescents and Youth Compared With Older Adults in 19 US States, Fall 2020.}, journal = {JAMA network open}, volume = {5}, number = {7}, pages = {e2222126}, pmid = {35838670}, issn = {2574-3805}, mesh = {Adolescent ; Aged ; *COVID-19/complications/epidemiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Humans ; Incidence ; Middle Aged ; Risk Factors ; SARS-CoV-2 ; United States/epidemiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Adolescents have been thought to be low in susceptibility to COVID-19 compared with older adults. Data regarding incidence and risk of COVID-19 are needed to convey risk of infection and inform prevention messaging, especially because US states such as Florida are recommending against vaccinating individuals ages 5 to 17 years and because more infections among adolescents could signal potentially higher incidence of long COVID.

OBJECTIVE: To compare incidence rates and relative risk of infection among US adolescents and youth with those of older adults for wild-type SARS-CoV-2.

This cross-sectional study included persons living in 19 US states that experienced surges from the start of the pandemic through fall 2020. Participants were all individuals reported as cases on state health department websites for the age groups and states studied. Age groups included adolescents (ages 10 to 19 years), youth (ages 15 to 24 years or 18 to 24 years), adolescents and youth combined (ages 10 to 24 years), and older adults (either age 60 years or 65 years and older), with age thresholds dependent on individual state data. Data were analyzed between June 2021 and January 2022.

MAIN OUTCOMES AND MEASURES: Incidence rates for the wild-type SARS-CoV-2 strain; the relative risk of infection in adolescents and youth compared with older adults, based on the incidence rate ratio (IRR).

RESULTS: In 16 of 19 states, the IRR of COVID-19 infection in adolescents and youth was significantly greater than in older adults. For example, in Florida, the incidence rate in adolescents and youth was 0.055 compared with 0.028 in older adults-adolescents and youth had 1.94 times the risk of contracting COVID-19 compared with older adults (IRR, 1.94; 95% CI, 1.92-1.95).

CONCLUSIONS AND RELEVANCE: Results from this cross-sectional study with US data were contrary to studies from Asia and Europe indicating lower susceptibility of adolescents than older adults. Our findings with the wild-type strain were consistent with findings reported in the UK for the Delta variant and underscored that even with the wild-type lineage, incidence among adolescents and youth exceeded that in older adults.}, } @article {pmid35838578, year = {2022}, author = {Troitskaya, LA and Plotnikova, IA and Avakyan, GG and Erokhina, VA and Badalyan, OL and Muraveva, AV and Zelentsova, VL and Khodko, OK and Safarova, ST and Shirokova, EI and Rusina, EA and Sanina, NP and Terentev, KV and Rachin, AP}, title = {Neuropsychological evaluation of cognitive disorders in children after COVID-19.}, journal = {European journal of translational myology}, volume = {32}, number = {3}, pages = {}, pmid = {35838578}, issn = {2037-7452}, abstract = {The article presents the results of neuropsychological remote and face-to-face testing of 25 children aged 12 to 17 years in the nearest (during and 1-2 weeks after the treatment) and later period (2-12 months) after COVID-19 infection with predominant respiratory tract infection, organized in Ekaterinburg in the State Autonomous Institution "Children's Hospital № 8". Indication of family contact with patients with a new coronavirus infection was found in all patients, a positive nasopharyngeal swab for SARS-CoV-2 RNA by PCR was found in 58%, non-focal neurological complaints were found in 54% of children. The control group consisted of 25 pupils of Moscow comprehensive schools (14 girls and 11 boys) aged between 12 and 16 years who were examined before the pandemic. The methods included: investigation of the kinesthetic, spatial, dynamic, graphic praxis; auditory-motor coordination; visual, object-constructive gnosis; auditory-speech, visual memory; voluntary attention; thinking. Significant differences with the results of neuropsychological tests performed in children in the control group were found, allowing us to assert impairment of memory, attention, visual gnosis, visual-spatial function, kinesthetic and dynamic praxis, verbal and non-verbal component of thinking. According to A.R. Luria's theory, the topic of the disorders involves the temporo-parieto-occipital, mediobasal, frontotemporal parts of the brain, the reticular formation and limbic structures. This necessitates the development of corrective educational programs and an in-depth diagnostic algorithm that determines the morphological substrate of cognitive disorders in children, who have undergone COVID-19.}, } @article {pmid35837086, year = {2022}, author = {Huynh, G and Nguyen, HV and Vo, LY and Le, NT and Nguyen, HTN}, title = {Assessment of Insomnia and Associated Factors Among Patients Who Have Recovered from COVID-19 in Vietnam.}, journal = {Patient preference and adherence}, volume = {16}, number = {}, pages = {1637-1647}, pmid = {35837086}, issn = {1177-889X}, abstract = {INTRODUCTION: The COVID-19 pandemic has been affecting the lives of millions of people globally. Patients recovering from COVID-19 are facing, not only the symptom of long COVID, but also psychological problems, such as sleep disturbance. This study aims to assess the proportion of COVID-19 recovered adult patients that suffer from insomnia and associated factors in Vietnam.

METHODS: A cross-sectional study was performed between January and March 2022 among patients who have recovered from a COVID-19 infection. Data were collected based on a self-administered questionnaire that included sociodemographic and standardized questionnaires from the Hospital Anxiety and Depression Scale (HADS), the Perceived stress scale (PSS) and the dependent variable using Insomnia Severity Index (ISI). Multivariable logistic regression was conducted to explore factors associated with the patients' insomnia disorder.

RESULTS: A total of 325 participants were included in this analysis, 34.5% of participants had insomnia. According to multivariable logistic regression, participants who were equal to and over 50 years of age, feeling alienated from others, and were not supported by families or relatives, reported significantly higher levels of insomnia disorders over those aged under 50 years, having closer ties with family and had received support from family or relatives. Besides, respondents who recorded mental health problems that included anxiety, depression and stress were more likely to get insomnia disorders than those without mental health symptoms (OR 2.7, 95% CI 1.1-6.6) (OR 4.5, 95% CI 2.3-8.9) (OR 2.3, 95% CI 1.1-5.3), respectively, all p < 0.05.

CONCLUSION: There was a remarkable rate of COVID-19 recovered patients experiencing insomnia disorders. Older age, alienated relationships and not being supported by families or relatives, as well as had mental health problems, are factors that affected the patients' insomnia, which showed that these sleep issues need to be screened and managed among adults who have recovered from COVID-19.}, } @article {pmid35836945, year = {2022}, author = {Motloch, LJ and Jirak, P and Gareeva, D and Davtyan, P and Gumerov, R and Lakman, I and Tataurov, A and Zulkarneev, R and Kabirov, I and Cai, B and Valeev, B and Pavlov, V and Kopp, K and Hoppe, UC and Lichtenauer, M and Fiedler, L and Pistulli, R and Zagidullin, N}, title = {Cardiovascular Biomarkers for Prediction of in-hospital and 1-Year Post-discharge Mortality in Patients With COVID-19 Pneumonia.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {906665}, pmid = {35836945}, issn = {2296-858X}, abstract = {AIMS: While COVID-19 affects the cardiovascular system, the potential clinical impact of cardiovascular biomarkers on predicting outcomes in COVID-19 patients is still unknown. Therefore, to investigate this issue we analyzed the prognostic potential of cardiac biomarkers on in-hospital and long-term post-discharge mortality of patients with COVID-19 pneumonia.

METHODS: Serum soluble ST2, VCAM-1, and hs-TnI were evaluated upon admission in 280 consecutive patients hospitalized with COVID-19-associated pneumonia in a single, tertiary care center. Patient clinical and laboratory characteristics and the concentration of biomarkers were correlated with in-hospital [Hospital stay: 11 days (10; 14)] and post-discharge all-cause mortality at 1 year follow-up [FU: 354 days (342; 361)].

RESULTS: 11 patients died while hospitalized for COVID-19 (3.9%), and 11 patients died during the 1-year post-discharge follow-up period (n = 11, 4.1%). Using multivariate analysis, VCAM-1 was shown to predict mortality during the hospital period (HR 1.081, CI 95% 1.035;1.129, p = 0.017), but not ST2 or hs-TnI. In contrast, during one-year FU post hospital discharge, ST2 (HR 1.006, 95% CI 1.002;1.009, p < 0.001) and hs-TnI (HR 1.362, 95% CI 1.050;1.766, p = 0.024) predicted mortality, although not VCAM-1.

CONCLUSION: In patients hospitalized with Covid-19 pneumonia, elevated levels of VCAM-1 at admission were associated with in-hospital mortality, while ST2 and hs-TnI might predict post-discharge mortality in long term follow-up.}, } @article {pmid35834042, year = {2022}, author = {Kuczborska, K and Buda, P and Książyk, J}, title = {Long-COVID in immunocompromised children.}, journal = {European journal of pediatrics}, volume = {181}, number = {9}, pages = {3501-3509}, pmid = {35834042}, issn = {1432-1076}, mesh = {*COVID-19/complications/epidemiology ; Child ; *Coronavirus Infections/diagnosis ; Humans ; Immunocompromised Host ; Pandemics ; *Pneumonia, Viral/diagnosis ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child's general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children - 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%). Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%).

CONCLUSIONS: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings.

WHAT IS KNOWN: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 - mainly mild or asymptomatic - among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups.

WHAT IS NEW: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.}, } @article {pmid35833897, year = {2022}, author = {Lobanov, AA and Irina A Grishechkina, and Andronov, SV and Gleb N Barashkov, and Andrey I Popov, and Anatoliy D Fesyun, and Elena P Ivanova, and Maccarone, MC and Stefano Masiero, }, title = {Can aquatic exercises contribute to the improvement of the gait stereotype function in patients with Long COVID outcomes?.}, journal = {European journal of translational myology}, volume = {32}, number = {3}, pages = {}, pmid = {35833897}, issn = {2037-7452}, abstract = {A variety of rehabilitation programmes can be offered to Long COVID patients, specifically physical training. Indeed 90% of these patients reports impairments of verticalization, stability and spatial orientation, making difficult exercise in the gym. The aim of our study was to assess the effectiveness and safety of aquatic exercise techniques as part of a comprehensive rehabilitation program for patients with Long COVID. The first of a two-stage program involved development of aquatic exercises technique, which was evaluated in 12 patients with impaired upright posture control before and after exercising by "Habilect" video gait analysis system. During the second phase, effectiveness and safety of aqua exercises were tested in water pool as part of a comprehensive rehabilitation programme conducted in 23 patients with Long COVID outcomes. Physical examination, 6-minute step test, Euro-QL-5D questionnaire, Borg scale, laser Doppler flowmetry, cardiointervalography, and spirometry were performed before and after the aquatic exercises program. After the training with aquatic exercises, indices of deviations of the main body axes of the head and the body mass centre ameliorated, as well as direction of body movement vector decreased (p<0.05). This study demonstrated a statistically significant improvement in exercise tolerance in both groups, as measured by the 6-minute step test after rehabilitation. The comparison group averaged 236.7 metres [126; 380] (T=8, p=0.047) after the rehabilitation course and the intervention group averaged 233.71 metres [150; 320] (T=8.0, p=0.047). When tested with the Euro-QL-5D questionnaire, a post-treatment improvement was noted in the comparison group on the anxiety/depression subscale (3 [3;3] (T=0, p=0.043)). In the intervention group, laser Doppler flowmetry revealed a statistically significant increase in microcirculation (6.36 standard units after rehabilitation) [5.54; 8.17] (T=7.0, p=0.004), and a decrease of oxidative metabolism index of 6.89 standard units. [4.76; 6.96] (T=4.0, p=0.03). No serious adverse events were reported. In conclusion, the developed aquatic exercises technique seems to contribute to recovery of impaired upright posture and motor function, normalizing the walking pattern.}, } @article {pmid35832113, year = {2022}, author = {Calloway, T and Hsiao, AF and Brand, M and Lai, J and Geise, C and Caceido, B and Alpert, R and Hollifield, M}, title = {Conceptualizing a Traditional Chinese Medicine and Pathology of Arousal Diagnostic and Pathophysiological Framework for Postacute Sequelae of COVID-19.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {167-171}, pmid = {35832113}, issn = {1933-6586}, abstract = {INTRODUCTION: The postacute sequelae of COVID-19 (PASC) is a serious heterogeneous condition that affects a significant minority of those who endured COVID-19. PASC involves multiple body systems and an illness trajectory that has stages now being identified in medical research.

OBJECTIVE: Traditional Chinese Medicine (TCM) and acupuncture are well suited to conceptualize and treat PASC and other postviral conditions. No description of TCM theory and its relationship with modern medical theory about PASC and its illness trajectory currently exists.

CONCLUSION: The authors provide an overview of the potential value of TCM for conceptualizing and treating PASC with a few examples and clarify directions for research.}, } @article {pmid35832109, year = {2022}, author = {Williams, JE and Moramarco, J}, title = {The Role of Acupuncture for Long COVID: Mechanisms and Models.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {159-166}, pmid = {35832109}, issn = {1933-6586}, abstract = {OBJECTIVE: To establish an evidence-based role for acupuncture as a safe and effective treatment for managing Long COVID in the integrative medical setting.

BACKGROUND: COVID-19 progresses to a chronic state, termed Long COVID, in about 30% of cases with estimates as high as 40% for prolonged illness. Symptoms are diverse and range over several body systems, including unrelenting fatigue, persistent malaise, chronic pain, and mood changes. Early clinical reports suggest acupuncture can effectively address both symptoms and the underlying causes of Long COVID.

EVIDENCE: Historically, acupuncture is well defined in Traditional Chinese Medicine writings to treat influenza-like febrile illnesses. Contemporary scientific literature and case studies support the value of acupuncture for symptoms associated with acute and chronic respiratory viral infections, such as influenza, including SARS and COVID-19. Recent reports provide early evidence of acupuncture's effectiveness in managing Long COVID symptoms and may also have disease-modifying benefits.

CONCLUSION: Acupuncture is a viable adjunctive health care modality as part of a multidisciplinary approach for symptom control and disease management to improve quality of life in Long COVID patients. Since acupuncture may favorably modify the length and outcome of this condition, the model of acupuncture presented in this article warrants broader use in the integrative clinical setting and for further research.}, } @article {pmid35832108, year = {2022}, author = {Hollifield, M and Cocozza, K and Calloway, T and Lai, J and Caicedo, B and Carrick, K and Alpert, R and Hsiao, AF}, title = {Improvement in Long-COVID Symptoms Using Acupuncture: A Case Study.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {172-176}, pmid = {35832108}, issn = {1933-6586}, abstract = {BACKGROUND: The long-COVID syndrome (LCS), defined by residual symptoms from acute COVID-19 for <60 days, affects about one-third of all COVID survivors and is an emerging public health challenge. Empirical data about the range of symptoms or the utility of acupuncture alone for the LCS are very limited.

CASE: This observational case study of a 46-year-old male with LCS was conducted to preliminarily define the range of symptoms, a Traditional Chinese Medicine (TCM) diagnostic structure, and evaluate the potential utility of prescribed acupuncture for LCS.

RESULTS: The primary TCM diagnostic patterns from this patient's LCS presentation included Lung Qi and Yin Deficiency, Qi and Blood Stagnation, and Spleen Qi Deficiency with dampness. Acupuncture for this patient was associated with reduced symptoms and signs of LCS.

CONCLUSION: A preliminary TCM diagnostic structure for LCS was defined. Acupuncture appears to have been helpful for a patient with LCS. Further research is needed to demonstrate the efficacy of acupuncture and/or other TCM modalities for LCS.}, } @article {pmid35832106, year = {2022}, author = {Stone, JAM}, title = {Long-COVID: Spotlight on National Institutes of Health Funding and Registered Trials.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {157-158}, doi = {10.1089/acu.2022.29206.jst}, pmid = {35832106}, issn = {1933-6586}, } @article {pmid35832078, year = {2022}, author = {Satta, S and Shahabipour, F and Gao, W and Lentz, SR and Perlman, S and Ashammakhi, N and Hsiai, T}, title = {Engineering viral genomics and nano-liposomes in microfluidic platforms for patient-specific analysis of SARS-CoV-2 variants.}, journal = {Theranostics}, volume = {12}, number = {10}, pages = {4779-4790}, pmid = {35832078}, issn = {1838-7640}, support = {UG3 TR003148/TR/NCATS NIH HHS/United States ; R01 HL129727/HL/NHLBI NIH HHS/United States ; R01 AI129269/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; R01 HL111437/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; *COVID-19/complications/diagnosis ; *Coronavirus Infections/prevention & control ; Genomics ; Humans ; Liposomes ; Microfluidics ; Mutation ; Pandemics/prevention & control ; Peptidyl-Dipeptidase A/metabolism ; *Pneumonia, Viral ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; }, abstract = {New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.}, } @article {pmid35822272, year = {2022}, author = {Muñoz-Corona, C and Gutiérrez-Canales, LG and Ortiz-Ledesma, C and Martínez-Navarro, LJ and Macías, AE and Scavo-Montes, DA and Guaní-Guerra, E}, title = {Quality of life and persistence of COVID-19 symptoms 90 days after hospital discharge.}, journal = {The Journal of international medical research}, volume = {50}, number = {7}, pages = {3000605221110492}, pmid = {35822272}, issn = {1473-2300}, mesh = {Arthralgia ; *COVID-19 ; Fatigue ; Hospitals ; Humans ; Patient Discharge ; *Quality of Life ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: We aimed to describe the persistence of symptoms in coronavirus disease 2019 (COVID-19) and quality of life (QoL) among patients 90 days after their discharge from the hospital for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine differences in QoL domains concerning the absence or presence of persistent symptoms.

METHODS: To measure QoL, we used a validated Spanish version of the 36-item Short Form Health Survey (SF-36).

RESULTS: We included 141 patients. Ninety days after discharge, COVID-19 symptoms persisted in 107 patients (75.9%), with fatigue (55.3%) and joint pain (46.8%) being the most frequent. According to the SF-36, the role-physical score was the dimension with the lowest values (median score, 25; interquartile range, 0-75). Patients with joint pain, fatigue, and dyspnea had lower scores than patients without those symptoms, with 10 of the 13 evaluated SF-36 scales showing lower levels.

CONCLUSION: Ninety days after hospital discharge from COVID-19 reference centers, most patients had persistent symptoms and had lower SF-36 scores than patients without symptoms. It is important to follow-up patients discharged from the hospital after SARS-CoV-2 infection, ideally through a post-COVID-19 health care clinic and rehabilitation program, to improve QoL in these patients.}, } @article {pmid35821795, year = {2022}, author = {Trager, RJ and Brewka, EC and Kaiser, CM and Patterson, AJ and Dusek, JA}, title = {Acupuncture in Multidisciplinary Treatment for Post-COVID-19 Syndrome.}, journal = {Medical acupuncture}, volume = {34}, number = {3}, pages = {177-183}, pmid = {35821795}, issn = {1933-6586}, abstract = {BACKGROUND: Post-COVID syndrome (PCS) is a complex, multisystem illness that may follow SARS-CoV-2/COVID-19 infection. As there is limited evidence for individual therapies and no singular treatment for PCS, guidelines endorse a multidisciplinary approach. This is a case report of a patient with PCS benefiting from a comprehensive approach including acupuncture with symptom-titrated physical activity (STPA).

CASE: A 50-year-old woman presented from a Long-COVID Clinic referral to an outpatient hospital-affiliated acupuncturist. She had 8 months of fatigue, anosmia, chest pressure, palpitations, and other symptoms following mild assay-confirmed COVID-19. Prior/concurrent medical testing revealed multisystem-inflammatory involvement (pericardial effusion, thyroid dysfunction, and elevated d-dimers). Cardiology/pulmonology cleared the patient for exercise to tolerance considering that serious pathology was absent. The acupuncturist's Traditional Chinese Medicine impression was of Qi Deficiency of the Heart, Lung, Spleen, and Kidney. This patient received 7 sessions of scalp, auricular, and body acupuncture. Physical-therapist (PT)-led STPA began 1-week post-acupuncture, involving 6 30-minute exercise sessions while monitoring her heart rate, with as-needed rest.

RESULTS: The patient's chest pressure and palpitations resolved after 1 acupuncture treatment. With 6 additional treatments, spanning 9 weeks, overlapping with PT-led SPTA, she recovered completely and resumed her normal exercise.

CONCLUSIONS: Acupuncture appeared to facilitate PCS recovery. However, the independent effects of acupuncture are less clear, given the concurrent STPA/exercise therapy, and should be explored using large study designs. Acupuncture is an attractive potential PCS therapy, considering its holistic approach and that it may be added to a multidisciplinary, guideline-concordant regimen.}, } @article {pmid35821571, year = {2022}, author = {Skilbeck, L}, title = {Patient-led integrated cognitive behavioural therapy for management of long COVID with comorbid depression and anxiety in primary care - A case study.}, journal = {Chronic illness}, volume = {18}, number = {3}, pages = {691-701}, doi = {10.1177/17423953221113605}, pmid = {35821571}, issn = {1745-9206}, mesh = {Adult ; Anxiety/complications/therapy ; *COVID-19/complications/therapy ; *Cognitive Behavioral Therapy ; Cost-Benefit Analysis ; Depression/complications/therapy ; Humans ; Male ; Primary Health Care ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Long COVID affects approximately ten-percent of people following post-acute Coronavirus infection. Long COVID is a complex, multisystemic recent illness. Therefore, there are currently no unitary guidelines on its management. The UK national guidelines currently recommended that interventions are guided by objective research evidence and subjective experiences of patients. They also emphasise multidisciplinary/interdisciplinary professional care and patient self-management.

METHODS: The current case study applied patient-led integrated cognitive behavioural therapy in a 36-year-old male presenting with long COVID symptoms with comorbid depression and anxiety. It applied integrated interdisciplinary CBT with emphasis on enhancing patient self-management. The patient attended twelve, individual, 60 min video sessions, via Microsoft Teams over a period of five months. The treatment was conducted in collaboration with the patient's general practitioner, physiotherapists and cardiopulmonary specialists. In line with the National Institute for Health and Care Excellence guidelines, it applied symptom monitoring, graded pacing and behavioural experiments.

RESULTS: At the end of therapy, the patient showed reliable change in his somatic symptoms, depression and anxiety symptoms. He also showed improved quality of life.

DISCUSSION: This case illustrates the effective use of patient-led CBT for managing symptoms of long COVID with comorbid depression and anxiety in primary care.}, } @article {pmid35820689, year = {2022}, author = {Davies, M}, title = {Long covid patients travel abroad for expensive and experimental "blood washing".}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o1671}, doi = {10.1136/bmj.o1671}, pmid = {35820689}, issn = {1756-1833}, mesh = {*COVID-19/complications/therapy ; Humans ; Medical Tourism ; Travel ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35818362, year = {2022}, author = {Zisis, SN and Durieux, JC and Mouchati, C and Perez, JA and McComsey, GA}, title = {The Protective Effect of Coronavirus Disease 2019 (COVID-19) Vaccination on Postacute Sequelae of COVID-19: A Multicenter Study From a Large National Health Research Network.}, journal = {Open forum infectious diseases}, volume = {9}, number = {7}, pages = {ofac228}, pmid = {35818362}, issn = {2328-8957}, support = {UL1 TR002548/TR/NCATS NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccines have been proven to decrease the severity of acute-phase infection; however, little is known about their effect on postacute sequelae of COVID-19 (PASC).

METHODS: Patients with confirmed COVID-19 diagnosis and minimum age of 18 years with 3-month follow-up postdiagnosis between 21 September 2020 and 14 December 2021 were identified from the TriNetX Research Network platform. The primary outcomes consisted of new-onset or persistent symptoms, new-onset diagnoses, and death and were compared between vaccine and no-vaccine groups.

RESULTS: At baseline, 1 578 719 patients with confirmed COVID-19 were identified and 1.6% (n = 25 225) completed vaccination. After matching, there were no differences (P > .05) in demographics or preexisting comorbidities. At 28 days following COVID-19 diagnosis, the incidence of hypertension was 13.52 per 1000, diabetes was 5.98 per 1000, thyroid disease was 3.80 per 1000, heart disease was 15.41 per 1000, and mental disorders was 14.77 per 1000 in the vaccine cohort. At 90 days following COVID-19 diagnosis, the relative risk of hypertension was 0.33 (95% confidence interval [CI], .26-.42), diabetes was 0.28 (95% CI, .20-.38), heart disease was 0.35 (95% CI, .29-.44), and death was 0.21 (95% CI, .16-.27). Differences in both 28- and 90-day risk between the vaccine and no-vaccine cohorts were observed for each outcome, and there was enough evidence (P < .05) to suggest that these differences were attributed to the vaccine.

CONCLUSIONS: Our data suggest that COVID-19 vaccine is protective against PASC symptoms, new onset of health conditions, and mortality.}, } @article {pmid35816778, year = {2022}, author = {Gallegos, M and Portillo, N and Martino, P and Cervigni, M}, title = {Long COVID-19: Rethinking mental health.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {77}, number = {}, pages = {100067}, pmid = {35816778}, issn = {1980-5322}, mesh = {*COVID-19/complications ; Humans ; *Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35816681, year = {2022}, author = {Ramiller, A and Mudie, K and Seibert, E and Whittaker, S}, title = {The Facilitation of Clinical and Therapeutic Discoveries in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Related Diseases: Protocol for the You + ME Registry Research Platform.}, journal = {JMIR research protocols}, volume = {11}, number = {8}, pages = {e36798}, pmid = {35816681}, issn = {1929-0748}, support = {U24 NS105535/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, have transformed the understanding of many complex illnesses, such as cancer and multiple sclerosis, by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS.

OBJECTIVE: This study aims to describe the protocol for the You + ME Registry, present preliminary results related to participant enrollment and satisfaction, and discuss the limitations of the registry as well as next steps.

METHODS: We developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with long COVID (LC), and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people.

RESULTS: As of September 30, 2021, the You + ME Registry had over 4200 geographically diverse participants (3033/4339, 69.9%, people with ME/CFS; 833/4339, 19.2%, post-COVID-19 people; and 473/4339, 10.9%, control volunteers), with an average of 72 new people registered every week. It has qualified as "great" using a net promotor score, indicating registrants are likely to recommend the registry to a friend. Analyses of collected data are currently underway, and preliminary findings are expected in the near future.

CONCLUSIONS: The You + ME Registry is an invaluable resource because it integrates with a symptom-tracking app, as well as a biorepository, to provide a robust and rich data set that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04806620; https://clinicaltrials.gov/ct2/show/NCT04806620.

DERR1-10.2196/36798.}, } @article {pmid35816258, year = {2022}, author = {Wurz, A and Culos-Reed, SN and Franklin, K and DeMars, J and Wrightson, JG and Twomey, R}, title = {"I feel like my body is broken": exploring the experiences of people living with long COVID.}, journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation}, volume = {31}, number = {12}, pages = {3339-3354}, pmid = {35816258}, issn = {1573-2649}, mesh = {Adult ; Female ; Humans ; *COVID-19 ; Quality of Life/psychology ; Emotions ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Long COVID, an illness affecting a subset of individuals after COVID-19, is distressing, poorly understood, and reduces quality of life. The objective of this sub-study was to better understand and explore individuals' experiences with long COVID and commonly reported symptoms, using qualitative data collected from open-ended survey responses.

METHODS: Data were collected from adults living with long COVID who participated in a larger observational online survey. Participants had the option of answering seven open-ended items. Data from the open-ended items were analyzed following guidelines for reflective thematic analysis.

RESULTS: From 213 participants who were included in the online survey, 169 participants who primarily self-identified as women (88.2%), aged 40-49 (33.1%), who had been experiencing long COVID symptoms for ≥ 6 months (74%) provided open-ended responses. Four overlapping and interconnected themes were identified: (1) Long COVID symptoms are numerous and wearing, (2) The effects of long COVID are pervasive, (3) Physical activity is difficult and, in some cases, not possible, and (4) Asking for help when few are listening, and little is working.

CONCLUSION: Findings reaffirm prior research, highlighting the complex nature of long COVID. Further, results show the ways individuals affected by the illness are negatively impacted and have had to alter their daily activities. Participants recounted the challenges faced when advocating for themselves, adapting to new limitations, and navigating healthcare systems. The varied relapsing-remitting symptoms, unknown prognosis, and deep sense of loss over one's prior identity suggest interventions are needed to support this population.}, } @article {pmid35814187, year = {2022}, author = {O'Kelly, B and Vidal, L and McHugh, T and Woo, J and Avramovic, G and Lambert, JS}, title = {Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study.}, journal = {Brain, behavior, & immunity - health}, volume = {24}, number = {}, pages = {100485}, pmid = {35814187}, issn = {2666-3546}, abstract = {BACKGROUND: Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial.

METHODS: In this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events.

FINDINGS: In total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2-49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171-396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054).

CONCLUSIONS: LDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.}, } @article {pmid35813874, year = {2022}, author = {Sumi, T and Harada, K}, title = {Immune response to SARS-CoV-2 in severe disease and long COVID-19.}, journal = {iScience}, volume = {25}, number = {8}, pages = {104723}, pmid = {35813874}, issn = {2589-0042}, abstract = {COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10% decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastically increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID.}, } @article {pmid35812220, year = {2022}, author = {Diniz, FC and Hipkiss, AR and Ferreira, GC}, title = {The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients.}, journal = {Frontiers in neuroscience}, volume = {16}, number = {}, pages = {898735}, pmid = {35812220}, issn = {1662-4548}, abstract = {Carnosine is a dipeptide expressed in both the central nervous system and periphery. Several biological functions have been attributed to carnosine, including as an anti-inflammatory and antioxidant agent, and as a modulator of mitochondrial metabolism. Some of these mechanisms have been implicated in the pathophysiology of coronavirus disease-2019 (COVID-19). COVID-19 is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The clinical manifestation and recovery time for COVID-19 are variable. Some patients are severely affected by SARS-CoV-2 infection and may experience respiratory failure, thromboembolic disease, neurological symptoms, kidney damage, acute pancreatitis, and even death. COVID-19 patients with comorbidities, including diabetes, are at higher risk of death. Mechanisms underlying the dysfunction of the afflicted organs in COVID-19 patients have been discussed, the most common being the so-called cytokine storm. Given the biological effects attributed to carnosine, adjuvant therapy with this dipeptide could be considered as supportive treatment in patients with either COVID-19 or long COVID.}, } @article {pmid35812094, year = {2022}, author = {Jacob, S and Kapadia, R and Soule, T and Luo, H and Schellenberg, KL and Douville, RN and Pfeffer, G}, title = {Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {914411}, pmid = {35812094}, issn = {1664-2295}, abstract = {In this article we review complications to the peripheral nervous system that occur as a consequence of viral infections, with a special focus on complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We discuss neuromuscular complications in three broad categories; the direct consequences of viral infection, autoimmune neuromuscular disorders provoked by viral infections, and chronic neurodegenerative conditions which have been associated with viral infections. We also include discussion of neuromuscular disorders that are treated by immunomodulatory therapies, and how this affects patient susceptibility in the current context of the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is associated with direct consequences to the peripheral nervous system via presumed direct viral injury (dysgeusia/anosmia, myalgias/rhabdomyolysis, and potentially mononeuritis multiplex) and autoimmunity (Guillain Barré syndrome and variants). It has important implications for people receiving immunomodulatory therapies who may be at greater risk of severe outcomes from COVID-19. Thus far, chronic post-COVID syndromes (a.k.a: long COVID) also include possible involvement of the neuromuscular system. Whether we may observe neuromuscular degenerative conditions in the longer term will be an important question to monitor in future studies.}, } @article {pmid35811273, year = {2022}, author = {Seghatchian, J and Pereira, P and Lanza, F}, title = {Spotlights on the latest opinions on identification, prevention, and management of newer CoV-2 variants: A roundup appraisal on innovative ideas and designer vaccines for Omicron.}, journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}, volume = {61}, number = {6}, pages = {103499}, pmid = {35811273}, issn = {1473-0502}, mesh = {Humans ; *COVID-19/prevention & control ; Communicable Disease Control ; SARS-CoV-2 ; *Vaccines ; Antibodies, Monoclonal ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although mass vaccination combined with some other preventative strategies and lockdown was associated with some early signs that COVID-19 infection might be fading away, the over 35 sites mutated new South African variant, "Omicron", emerged almost globally. Certain predisposed hosts may develop severe inflammatory thrombotic or mild long-Covid conditions due to this variant, which depletes T-cells, neutralizes antibodies circulating in the body, and coincidentally induces hypercoagulability. The surge of Omicron combined with Delta variants may confer unresponsiveness to the currently available vaccines even when the second dose is given up to 90 days. A drop in the antibody levels by 30 % has been identified in omicron-infected individuals, and one in five people is resistant to antibody treatment. This poses major concerns in the transmissibility rate of this new variant, even in a heavy mass vaccinated environment. This heavily mutated Omicron with other spike sites facilitates viral entry into the cells through conformational changes, irrespective of circulating neutralising antibody. Based on this consideration, we believe that speeding up mixed-matched vaccines with higher T-cell stimulation ability may improve the current situation. Moreover, large orders for antiviral drugs and monoclonal antibodies that could tackle Omicron combined with other variants may be valuable. The use of free polyclonal antibody donations and, hopefully, T-cell immunotherapy, may represent further breakthrough therapeutic interventions. However, Omicron infection is relatively milder than the ongoing Delta variant but is extremely contagious, and therefore the development of novel interventions is highly demanding.}, } @article {pmid35811082, year = {2022}, author = {Petersen, MS and Í Kongsstovu, S and Eliasen, EH and Larsen, S and Hansen, JL and Vest, N and Dahl, MM and Christiansen, DH and Møller, LF and Kristiansen, MF}, title = {Clinical characteristics of the Omicron variant - results from a Nationwide Symptoms Survey in the Faroe Islands.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {122}, number = {}, pages = {636-643}, pmid = {35811082}, issn = {1878-3511}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Child ; Cross-Sectional Studies ; Humans ; *SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Omicron appears to lead to a milder illness for patients compared with previous COVID-19 variants. However, not all infected with Omicron would describe their illness as mild. In this study, we investigate the experienced severity and symptoms of the Omicron variant.

METHODS: We conducted a nationwide cross-sectional study, including 5036 individuals of all ages, consisting of reverse transcription-polymerase chain reaction confirmed SARS-CoV-2 cases from 1 January to 31 January 2022 (n = 4506) and a control group without SARS-COV-2 infection in December 2021 or January 2022 (n = 530). Omicron was dominant during this period. Cases were asked about their acute symptoms and answered a web-based questionnaire 10-30 days after their positive test while controls were asked about symptoms during the past week.

RESULTS: Among cases, 97% reported at least one symptom during the acute phase compared with 79% of controls. Just over half the cases assessed their illness as asymptomatic or mild, whereas 46% assessed their illness as moderate or severe. Children reported fewer symptoms and less severe illnesses than adults (P <0.001). The largest risk differences (RDs) between adult cases and controls due to symptoms were observed for fever (RD = 60.6%, confidence interval [CI] 57.4-63.6), fatigue (RD = 49.6%, CI 44.1-54.7), and chills (RD = 48.8%, CI 43.8-53.2).

CONCLUSION: Most of those infected with Omicron experience symptoms, and the Omicron variant appears to lead to less severe disease. However, this does not mean that all the infected experience an Omicron infection as mild. The unprecedented rate of Omicron infections worldwide leads to urgent questions about the rate of long COVID after Omicron infections.}, } @article {pmid35808102, year = {2022}, author = {Wu, Y and Rakotoarisoa, M and Angelov, B and Deng, Y and Angelova, A}, title = {Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {12}, number = {13}, pages = {}, pmid = {35808102}, issn = {2079-4991}, support = {CZ.02.1.01/0.0/0.0/15_003/0000447 "Structural Dynamics of Biomolecular Systems" (ELIBIO)//European Regional Development Fund/ ; CZ.02.1.01/0.0/0.0/16_019/0000789 "Advanced research using high-intensity laser produced photons and particles"//European Regional Development Fund/ ; 3+3 program, No. 204, item 27 from 25.03.2020//JINR, Dubna/ ; WIUCASQD2019005//Wenzhou Institute, University of Chinese Academy of Sciences/ ; 31670841//National Natural Science Foundation China/ ; ANR-11-IDEX-0003-02 "IDI 2017" IDEX Paris-Saclay//Agence Nationale de la Recherche France/ ; }, abstract = {Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide-drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.}, } @article {pmid35807916, year = {2022}, author = {Semmarath, W and Mapoung, S and Umsumarng, S and Arjsri, P and Srisawad, K and Thippraphan, P and Yodkeeree, S and Dejkriengkraikul, P}, title = {Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway.}, journal = {Nutrients}, volume = {14}, number = {13}, pages = {}, pmid = {35807916}, issn = {2072-6643}, support = {FF65/025//The Fundamental Fund 2022, Chiang Mai University/ ; PHD/0126/2559//The Royal Golden Jubilee Scholarship PhD. Program (RGJ)/ ; }, mesh = {Anthocyanins/pharmacology ; *COVID-19/complications ; Glucosides/pharmacology ; Humans ; Inflammasomes ; Interleukin-18 ; Lung/metabolism ; Macrophages/metabolism ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; *Oryza/metabolism ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; }, abstract = {Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G and P3G-rich fraction of black rice germ and bran (BR extract) on the inhibition of inflammatory responses induced by SP, as well as the inhibition of NF-kB activation and the NLRP3 inflammasome pathway in an in vitro model. In this study, BR extract was identified for its active anthocyanins, C3G and P3G, using the HPLC technique. A549-lung cells and differentiated THP-1 macrophages were treated with BR extract, C3G, or P3G prior to exposure to 100 ng/mL of SP. Their anti-inflammatory properties were then determined. BR extract at concentrations of 12.5−100 μg/mL exhibited anti-inflammation activity for both A549 and THP-1 cells through the significant suppression of NLRP3, IL-1β, and IL-18 inflammatory gene expressions and IL-6, IL-1β, and IL-18 cytokine secretions in a dose-dependent manner (p < 0.05). It was determined that both cell lines, C3G and P3G (at 1.25−10 μg/mL), were compatibly responsible for the significant inhibition of SP-induced inflammatory responses for both gene and protein levels (p < 0.05). With regard to the anti-inflammation mechanism, BR extract, C3G, and P3G could attenuate SP-induced inflammation via counteraction with NF-kB activation and downregulation of the inflammasome-dependent inflammatory pathway proteins (NLRP3, ASC, and capase-1). Overall, the protective effects of anthocyanins obtained from black rice germ and bran can be employed in potentially preventive strategies that use pigmented rice against the long-term sequelae of COVID-19 infection.}, } @article {pmid35806901, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Pellicer-Valero, ÓJ and Navarro-Pardo, E and Gómez-Mayordomo, V and Cuadrado, ML and Arias-Navalón, JA and Cigarán-Méndez, M and Hernández-Barrera, V and Arendt-Nielsen, L}, title = {Reply to Ayuso García et al. Health Perception among Female COVID-19 Patients. Comment on "Fernández-de-las-Peñas et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J. Clin. Med. 2022, 11, 413".}, journal = {Journal of clinical medicine}, volume = {11}, number = {13}, pages = {}, pmid = {35806901}, issn = {2077-0383}, abstract = {We have read with great interest the comment by Ayuso García et al [...].}, } @article {pmid35806214, year = {2022}, author = {Szewczykowski, C and Mardin, C and Lucio, M and Wallukat, G and Hoffmanns, J and Schröder, T and Raith, F and Rogge, L and Heltmann, F and Moritz, M and Beitlich, L and Schottenhamml, J and Herrmann, M and Harrer, T and Ganslmayer, M and Kruse, FE and Kräter, M and Guck, J and Lämmer, R and Zenkel, M and Gießl, A and Hohberger, B}, title = {Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.}, journal = {International journal of molecular sciences}, volume = {23}, number = {13}, pages = {}, pmid = {35806214}, issn = {1422-0067}, support = {01EP2108A//Federal Ministry of Education and Research/ ; }, mesh = {Adrenergic Agents ; Autoantibodies ; *COVID-19/complications ; Female ; Humans ; Microcirculation ; Receptors, G-Protein-Coupled ; Retinal Vessels ; SARS-CoV-2 ; Tomography, Optical Coherence ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT-angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.}, } @article {pmid35805671, year = {2022}, author = {Mińko, A and Turoń-Skrzypińska, A and Rył, A and Tomska, N and Bereda, Z and Rotter, I}, title = {Searching for Factors Influencing the Severity of the Symptoms of Long COVID.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {13}, pages = {}, pmid = {35805671}, issn = {1660-4601}, mesh = {Aged ; *COVID-19/complications/epidemiology ; Delivery of Health Care ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is a highly contagious respiratory disease. Infection with the virus can occur with differing symptom severity, from mild and moderate to severe cases, but the long-term consequences of infection have not been fully identified or studied. Long COVID is defined as occurring in individuals with a history of probable or confirmed SARS-CoV-2 infection, and symptoms persisting for at least two months within three months of onset that cannot be explained by an alternative diagnosis. The purpose of this study was to look for factors that influence the type and severity of Long COVID symptoms. In total, 932 individuals with a history of COVID-19 were qualified for the study using an original questionnaire based on the COVID-19 Yorkshire Rehab Screen (C19-YRS) questionnaire. Older adults were more likely to report problems with mobility (p < 0.001) and in performing daily activities (p = 0.014). Those with a higher BMI showed significantly more symptoms such as dyspnea at rest (p < 0.001) and on exertion (p < 0.001), feelings of chronic fatigue (p = 0.023), problems with mobility (p < 0.001), and in performing daily activities (p = 0.002). The data show that those with Long COVID should receive multidisciplinary help including additional medical and psychological support. Particular attention should be paid to elderly and obese persons, who should be included in rehabilitation programs after COVID-19 in the first place.}, } @article {pmid35805406, year = {2022}, author = {Houben, S and Bonnechère, B}, title = {The Impact of COVID-19 Infection on Cognitive Function and the Implication for Rehabilitation: A Systematic Review and Meta-Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {13}, pages = {}, pmid = {35805406}, issn = {1660-4601}, mesh = {*COVID-19 ; Cognition ; Humans ; }, abstract = {There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. This prolonged COVID-19 pathology is often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post-COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub-functions level. Therefore, we first aim to summarize the current level of evidence supporting the negative impact of COVID-19 infection on cognitive functions. Twenty-seven studies were included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3786 healthy controls). We then performed a meta-analysis summarizing the results of five studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in standardized mean differences, is -0.41 [95%CI -0.55; -0.27]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and avoid long-term complications.}, } @article {pmid35804058, year = {2022}, author = {Wu, Q and Ailshire, JA and Crimmins, EM}, title = {Long COVID and symptom trajectory in a representative sample of Americans in the first year of the pandemic.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11647}, pmid = {35804058}, issn = {2045-2322}, support = {P30 AG017265/AG/NIA NIH HHS/United States ; U01 AG054580/AG/NIA NIH HHS/United States ; }, mesh = {*COVID-19/complications/epidemiology ; Headache/epidemiology ; Humans ; *Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {People who have COVID-19 can experience symptoms for months. Studies on long COVID in the population lack representative samples and longitudinal data focusing on new-onset symptoms occurring with COVID while accounting for pre-infection symptoms. We use a sample representing the U.S. community population from the Understanding America Study COVID-19 Survey, which surveyed around 8000 respondents bi-weekly from March 2020 to March 2021. Our final sample includes 308 infected individuals who were interviewed one month before, around the time of, and 12 weeks after infection. About 23% of the sample experienced new-onset symptoms during infection which lasted for more than 12 weeks, and thus can be considered as having long COVID. The most common new-onset persistent symptoms among those included in the study were headache (22%), runny or stuffy nose (19%), abdominal discomfort (18%), fatigue (17%), and diarrhea (13%). Long COVID was more likely among obese individuals (OR = 5.44, 95% CI 2.12-13.96) and those who experienced hair loss (OR = 6.94, 95% CI 1.03-46.92), headache (OR = 3.37, 95% CI 1.18-9.60), and sore throat (OR = 3.56, 95% CI 1.21-10.46) during infection. There was a lack of evidence relating risk to age, gender, race/ethnicity, education, current smoking status, or comorbid chronic conditions. This work provides national estimates of long COVID in a representative sample after accounting for pre-infection symptoms.}, } @article {pmid35800257, year = {2022}, author = {Peluso, MJ and Anglin, K and Durstenfeld, MS and Martin, JN and Kelly, JD and Hsue, PY and Henrich, TJ and Deeks, SG}, title = {Effect of Oral Nirmatrelvir on Long COVID Symptoms: 4 Cases and Rationale for Systematic Studies.}, journal = {Pathogens & immunity}, volume = {7}, number = {1}, pages = {95-103}, pmid = {35800257}, issn = {2469-2964}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Efforts to understand the impact of SARS-CoV-2 variants, vaccine status, and treatment on the development and persistence of Long COVID have intensified.

METHODS: We report 4 sequential cases from a post-COVID cohort study demonstrating variability in outcomes following differentially timed nirmatrelvir therapy, received as part of clinical care.

RESULTS: In the first case, the participant experienced symptomatic rebound and developed Long COVID despite early initiation of antiviral therapy. In the next 2 cases, participants reported improvement in persistent COVID symptoms when nirmatrelvir was taken 25 and 60 days following initial symptom onset. In the final case, an individual with presumed Long COVID for 2 years reported substantial improvement in chronic symptoms when taking nirmatrelvir following SARS-CoV-2 re-infection.

CONCLUSIONS: These anecdotes suggest that systematic study of antiviral therapy for Long COVID is warranted.}, } @article {pmid35798818, year = {2022}, author = {Lee, Y and Riskedal, E and Kalleberg, KT and Istre, M and Lind, A and Lund-Johansen, F and Reiakvam, O and Søraas, AVL and Harris, JR and Dahl, JA and Hadley, CL and Jugessur, A}, title = {EWAS of post-COVID-19 patients shows methylation differences in the immune-response associated gene, IFI44L, three months after COVID-19 infection.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11478}, pmid = {35798818}, issn = {2045-2322}, mesh = {*Autoimmune Diseases/genetics ; *COVID-19/complications/genetics ; Cohort Studies ; DNA Methylation ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although substantial progress has been made in managing COVID-19, it is still difficult to predict a patient's prognosis. We explored the epigenetic signatures of COVID-19 in peripheral blood using data from an ongoing prospective observational study of COVID-19 called the Norwegian Corona Cohort Study. A series of EWASs were performed to compare the DNA methylation profiles between COVID-19 cases and controls three months post-infection. We also investigated differences associated with severity and long-COVID. Three CpGs-cg22399236, cg03607951, and cg09829636-were significantly hypomethylated (FDR < 0.05) in COVID-19 positive individuals. cg03607951 is located in IFI44L which is involved in innate response to viral infection and several systemic autoimmune diseases. cg09829636 is located in ANKRD9, a gene implicated in a wide variety of cellular processes, including the degradation of IMPDH2. The link between ANKRD9 and IMPDH2 is striking given that IMPDHs are considered therapeutic targets for COVID-19. Furthermore, gene ontology analyses revealed pathways involved in response to viruses. The lack of significant differences associated with severity and long-COVID may be real or reflect limitations in sample size. Our findings support the involvement of interferon responsive genes in the pathophysiology of COVID-19 and indicate a possible link to systemic autoimmune diseases.}, } @article {pmid35798378, year = {2022}, author = {Strain, D}, title = {Removing special covid leave will only undervalue staff and threaten patient safety.}, journal = {BMJ (Clinical research ed.)}, volume = {378}, number = {}, pages = {o1684}, doi = {10.1136/bmj.o1684}, pmid = {35798378}, issn = {1756-1833}, mesh = {*COVID-19 ; Employment ; Humans ; *Patient Safety ; Personal Protective Equipment ; }, } @article {pmid35797498, year = {2023}, author = {Woltsche, JN and Horwath-Winter, J and Dorn, C and Boldin, I and Steinwender, G and Heidinger, A and Woltsche, N}, title = {Neuropathic Corneal Pain as Debilitating Manifestation of LONG-COVID.}, journal = {Ocular immunology and inflammation}, volume = {31}, number = {6}, pages = {1216-1218}, doi = {10.1080/09273948.2022.2090963}, pmid = {35797498}, issn = {1744-5078}, mesh = {Female ; Humans ; Cornea/innervation ; *COVID-19/complications ; Microscopy, Confocal ; *Neuralgia/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {This report illustrates the case of a female patient suffering from severe ocular discomfort, tinnitus and ageusia, 7 months after a SARS-CoV-2 infection. The medical history implicated a diagnosis of LONG-COVID with ocular pain as the most debilitating symptom. In-vivo confocal microscopy revealed corneal microneuromas with hyperreflectivity and irregular enlargement of nerve endings in both eyes, which led to the diagnosis of neuropathic corneal pain. The aim of this report is to increase awareness that COVID-19 induced neuropathic pain can also occur in the cornea representing the human body's most richly innervated tissue.}, } @article {pmid35797144, year = {2022}, author = {Caorsi, R and Civino, A and Ravelli, A}, title = {Complications of severe acute respiratory syndrome coronavirus 2 infection in children.}, journal = {Current opinion in rheumatology}, volume = {34}, number = {5}, pages = {267-273}, doi = {10.1097/BOR.0000000000000892}, pmid = {35797144}, issn = {1531-6963}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Although during the initial stages of COVID-19 pandemic, the pediatric population seemed to be less affected, a number of SARS-CoV-2-related manifestations emerged over time, the principal of which is the multisystem inflammatory syndrome in children (MIS-C). Here we provide an update on the main pediatric disorders associated with SARS-CoV-2 infection.

RECENT FINDINGS: MIS-C is novel postinfectious manifestation with clinical features similar to Kawasaki disease and characterized by intense systemic inflammation affecting multiple organs. Many children required intensive care therapy because of circulatory shock, usually of myocardial origin. Appropriate treatment with immunomodulatory therapies led to favorable outcomes in most patients, with recovery of overall health and cardiac dysfunction. In addition to MIS-C, a variety of other complications of COVID-19 in children have been described, including thrombotic events, neurologic manifestations, and chilblain-like lesions. There is still uncertainty about the true prevalence of long COVID in children and its distinction from pandemic-related complaints.

SUMMARY: The experience gained so far with MIS-C and the other SARS-CoV-2-related complications in children and adolescents will facilitate accurate diagnosis and appropriate treatment. Further studies are needed to elucidate the pathophysiology of MIS-C and to determine the real impact of long-COVID in the pediatric age group.}, } @article {pmid35796131, year = {2022}, author = {Azzolini, E and Levi, R and Sarti, R and Pozzi, C and Mollura, M and Mantovani, A and Rescigno, M}, title = {Association Between BNT162b2 Vaccination and Long COVID After Infections Not Requiring Hospitalization in Health Care Workers.}, journal = {JAMA}, volume = {328}, number = {7}, pages = {676-678}, pmid = {35796131}, issn = {1538-3598}, mesh = {*BNT162 Vaccine ; *COVID-19/complications/prevention & control ; *Health Personnel ; Hospitalization ; Humans ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {This study examines the risk of long COVID following mRNA vaccination, compared with no vaccination, in health care workers in Italy who had COVID-19 infection.}, } @article {pmid35794549, year = {2022}, author = {Pazukhina, E and Andreeva, M and Spiridonova, E and Bobkova, P and Shikhaleva, A and El-Taravi, Y and Rumyantsev, M and Gamirova, A and Bairashevskaia, A and Petrova, P and Baimukhambetova, D and Pikuza, M and Abdeeva, E and Filippova, Y and Deunezhewa, S and Nekliudov, N and Bugaeva, P and Bulanov, N and Avdeev, S and Kapustina, V and Guekht, A and DunnGalvin, A and Comberiati, P and Peroni, DG and Apfelbacher, C and Genuneit, J and Reyes, LF and Brackel, CLH and Fomin, V and Svistunov, AA and Timashev, P and Mazankova, L and Miroshina, A and Samitova, E and Borzakova, S and Bondarenko, E and Korsunskiy, AA and Carson, G and Sigfrid, L and Scott, JT and Greenhawt, M and Buonsenso, D and Semple, MG and Warner, JO and Olliaro, P and Needham, DM and Glybochko, P and Butnaru, D and Osmanov, IM and Munblit, D and , }, title = {Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID).}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {244}, pmid = {35794549}, issn = {1741-7015}, support = {MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *COVID-19/epidemiology ; Child ; Cohort Studies ; Female ; Hospitals ; Humans ; *Hypertension ; Moscow/epidemiology ; Patient Discharge ; Prevalence ; Prospective Studies ; Risk Factors ; }, abstract = {BACKGROUND: Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors.

METHODS: Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge.

RESULTS: One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47-53) in adults and 20% (95% CI 16-24) in children at 6 months, with decline to 34% (95% CI 31-37) and 11% (95% CI 8-14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47).

CONCLUSIONS: Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.}, } @article {pmid35793922, year = {2022}, author = {Daines, L and Mulholland, RH and Vasileiou, E and Hammersley, V and Weatherill, D and Katikireddi, SV and Kerr, S and Moore, E and Pesenti, E and Quint, JK and Shah, SA and Shi, T and Simpson, CR and Robertson, C and Sheikh, A}, title = {Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.}, journal = {BMJ open}, volume = {12}, number = {7}, pages = {e059385}, pmid = {35793922}, issn = {2044-6055}, support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; MC_PC_19075/MRC_/Medical Research Council/United Kingdom ; COV/LTE/20/15/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; Hospitalization ; Humans ; Observational Studies as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

METHODS AND ANALYSIS: We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.

ETHICS AND DISSEMINATION: The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.}, } @article {pmid35791687, year = {2022}, author = {Tobinick, E and Spengler, RN and Ignatowski, TA and Wassel, M and Laborde, S}, title = {Rapid improvement in severe long COVID following perispinal etanercept.}, journal = {Current medical research and opinion}, volume = {38}, number = {12}, pages = {2013-2020}, doi = {10.1080/03007995.2022.2096351}, pmid = {35791687}, issn = {1473-4877}, mesh = {Humans ; Etanercept/therapeutic use ; Receptors, Tumor Necrosis Factor/therapeutic use ; *COVID-19/complications ; Immunoglobulin G/therapeutic use ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha ; *Stroke/drug therapy ; Fatigue ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: This study aimed to describe the neurological improvements in a patient with severe long COVID brain dysfunction following perispinal etanercept administration. Perispinal administration of etanercept, a novel method designed to enhance its brain delivery via carriage in the cerebrospinal venous system, has previously been shown to reduce chronic neurological dysfunction after stroke. Etanercept is a recombinant biologic that is capable of ameliorating two components of neuroinflammation: microglial activation and the excess bioactivity of tumor necrosis factor (TNF), a proinflammatory cytokine that is a key neuromodulator in the brain. Optimal synaptic and brain network function require physiological levels of TNF. Neuroinflammation, including brain microglial activation and excess central TNF, can be a consequence of stroke or peripheral infection, including infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.

METHODS: Standardized, validated measures, including the Montreal Cognitive Assessment, Beck Depression Index-II (BDI-II), Fatigue Assessment Scale, Controlled Oral Word Association Test, Trail Making Tests, Timed Finger-to-Nose Test, 20 m Self-Paced Walk Test, 5 Times Sit-to-Stand Test and Grip Strength measured with a Jamar Dynamometer were used to quantitate changes in cognition, depression, fatigue and neurological function after a single 25 mg perispinal etanercept dose in a patient with severe long COVID of 12 months duration.

RESULTS: Following perispinal etanercept administration there was immediate neurological improvement. At 24 h, there were remarkable reductions in chronic post-COVID-19 fatigue and depression, and significant measurable improvements in cognition, executive function, phonemic verbal fluency, balance, gait, upper limb coordination and grip strength. Cognition, depression and fatigue were examined at 29 days; each remained substantially improved.

CONCLUSION: Perispinal etanercept is a promising treatment for the chronic neurologic dysfunction that may persist after resolution of acute COVID-19, including chronic cognitive dysfunction, fatigue, and depression. These results suggest that long COVID brain neuroinflammation is a potentially reversible pathology and viable treatment target. In view of the increasing unmet medical need, clinical trials of perispinal etanercept for long COVID are urgently necessary. The robust results of the present case suggest that perispinal etanercept clinical trials studying long COVID populations with severe fatigue, depression and cognitive dysfunction may have improved ability to detect a treatment effect. Positron emission tomographic methods that image brain microglial activation and measurements of cerebrospinal fluid proinflammatory cytokines may be useful for patient selection and correlation with treatment effects, as well as provide insight into the underlying pathophysiology.}, } @article {pmid35789882, year = {2022}, author = {Norredam, M and Hayward, S and Deal, A and Agyemang, C and Hargreaves, S}, title = {Understanding and addressing long-COVID among migrants and ethnic minorities in Europe.}, journal = {The Lancet regional health. Europe}, volume = {19}, number = {}, pages = {100427}, pmid = {35789882}, issn = {2666-7762}, } @article {pmid35788744, year = {2022}, author = {Muñoz-Jurado, A and Escribano, BM and Agüera, E and Caballero-Villarraso, J and Galván, A and Túnez, I}, title = {SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19.}, journal = {Journal of neurology}, volume = {269}, number = {9}, pages = {4581-4603}, pmid = {35788744}, issn = {1432-1459}, mesh = {Antibodies, Viral ; *COVID-19/complications ; COVID-19 Vaccines/adverse effects ; Humans ; *Multiple Sclerosis/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 pandemic has raised particular concern for people with Multiple Sclerosis, as these people are believed to be at increased risk of infection, especially those being treated with disease-modifying therapies. Therefore, the objective of this review was to describe how COVID-19 affects people who suffer from Multiple Sclerosis, evaluating the risk they have of suffering an infection by this virus, according to the therapy to which they are subjected as well as the immune response of these patients both to infection and vaccines and the neurological consequences that the virus can have in the long term. The results regarding the increased risk of infection due to treatment are contradictory. B-cell depletion therapies may cause patients to have a lower probability of generating a detectable neutralizing antibody titer. However, more studies are needed to help understand how this virus works, paying special attention to long COVID and the neurological symptoms that it causes.}, } @article {pmid35787541, year = {2022}, author = {Pai, N and Vella, SL}, title = {The physical and mental health consequences of social isolation and loneliness in the context of COVID-19.}, journal = {Current opinion in psychiatry}, volume = {35}, number = {5}, pages = {305-310}, pmid = {35787541}, issn = {1473-6578}, mesh = {*COVID-19/complications ; Humans ; *Loneliness/psychology ; Mental Health ; Pandemics ; Social Isolation/psychology ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Social isolation and loneliness are known contributors to all-cause mortality as well as a range of physical and mental health conditions. Therefore, this article reviews current literature pertaining to the effects of social isolation and loneliness on physical and mental health during the current COVID-19 pandemic.

RECENT FINDINGS: Social isolation and loneliness contribute to a myriad of physical and mental health conditions. Specifically social isolation and loneliness contribute to the development of cardiovascular disease, diabetes mellitus, and cancer. However, most research indicated that poor lifestyle factors explained most of the association. Social isolation and loneliness are also associated with cognitive problems including dementia, immune system problems, and mental health conditions. Further social isolation and loneliness also spur behavioral issues that significantly affect physical and mental health.

SUMMARY: Evidence suggests that social isolation and loneliness have significant consequences on the physical and mental health of the individual and that the move toward ending all protections against COVID-19 has significant implications for the vulnerable. Further the similarities between the effects of social isolation and loneliness are compared to some of the conditions evident in long-COVID.}, } @article {pmid35787539, year = {2022}, author = {Poonja, S and Chaudhuri, KR and Miyasaki, JM}, title = {Movement disorders in COVID-19 times: impact on care in movement disorders and Parkinson disease.}, journal = {Current opinion in neurology}, volume = {35}, number = {4}, pages = {494-501}, pmid = {35787539}, issn = {1473-6551}, mesh = {*COVID-19/complications/epidemiology ; Humans ; *Movement Disorders/epidemiology/therapy ; Pandemics ; *Parkinson Disease/epidemiology/therapy ; SARS-CoV-2 ; *Telemedicine ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP).

RECENT FINDINGS: As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine.

SUMMARY: COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.}, } @article {pmid35785594, year = {2022}, author = {Pinzon, RT and Wijaya, VO and Jody, AA and Nunsio, PN and Buana, RB}, title = {Persistent neurological manifestations in long COVID-19 syndrome: A systematic review and meta-analysis.}, journal = {Journal of infection and public health}, volume = {15}, number = {8}, pages = {856-869}, pmid = {35785594}, issn = {1876-035X}, mesh = {*COVID-19/complications ; *Coronavirus Infections/epidemiology ; Humans ; Pandemics ; *Pneumonia, Viral/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Several studies have reported prolonged symptoms especially neurological symptoms following acute infection in patients with COVID-19, known as long COVID-19. There are only few studies investigating this population and relatively less known, including nervous system involvement. A systematic review and meta-analysis of these studies are required to understanding the prevalence of persistent neurological manifestations after COVID-19.

OBJECTIVE: To conduct a systematic review and meta-analysis on the persistent neurological manifestations in COVID-19 survivors.

METHODS: Authors conducted a literature search through PubMed and MedRxiv from January 1st, 2020 to October 2021 according to PRISMA guideline. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of long COVID-19 patients in their data were included. Case reports and case series also included in this review. The quality of the studies was assessed based on the Oxford Centre for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and heterogeneity test.

FINDINGS: From 128 identified studies, 36 were eligible, with 9944 participants included. Most of the included studies had mean duration of follow-up after COVID-19 onset of less than 6 months. Fatigue was the most common (52.8%, 95%CI 19.9 - 84.4) symptoms of long COVID, followed by cognitive disorder (35.4%, 95%CI 2.1 - 81.7); paresthesia (33.3%, 95%CI 2.7 - 76.6); sleep disorder (32.9%, 95%CI 6.5 - 67.4); musculoskeletal pain (27.8%, 95%CI 12.7 - 46); and dizziness (26.4%, 95%CI 4.6 - 57.9).

CONCLUSION: Neurological manifestations are prevalent and persisting in patients with long COVID. The duration of the symptoms are vary among literatures. However, the frequency are mostly observed during the first six months after the illness onset.}, } @article {pmid35785029, year = {2022}, author = {Szukiewicz, D and Wojdasiewicz, P and Watroba, M and Szewczyk, G}, title = {Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {9534163}, pmid = {35785029}, issn = {2314-7156}, mesh = {*COVID-19/complications ; Female ; Humans ; *Mast Cell Activation Syndrome ; *Mastocytosis ; Pregnancy ; *Pregnancy Complications, Infectious ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19), a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can affect almost all systems and organs of the human body, including those responsible for reproductive function in women. The multisystem inflammatory response in COVID-19 shows many analogies with mast cell activation syndrome (MCAS), and MCAS may be an important component in the course of COVID-19. Of note, the female sex hormones estradiol (E2) and progesterone (P4) significantly influence mast cell (MC) behavior. This review presents the importance of MCs and the mediators from their granules in the female reproductive system, including pregnancy, and discusses the mechanism of potential disorders related to MCAS. Then, the available data on COVID-19 in the context of hormonal disorders, the course of endometriosis, female fertility, and the course of pregnancy were compiled to verify intuitively predicted threats. Surprisingly, although COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in MCAS, the available clinical data do not provide grounds for treating this mechanism as significantly increasing the risk of abnormal female reproductive function, including pregnancy. Further studies in the context of post COVID-19 condition (long COVID), where inflammation and a procoagulative state resemble many aspects of MCAS, are needed.}, } @article {pmid35784994, year = {2022}, author = {Warren, BC and Bond, T and Hessler, R and Boldt, J}, title = {Primary Paraganglioma of the Lung in an Asymptomatic Patient.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e25562}, pmid = {35784994}, issn = {2168-8184}, abstract = {Arising from the autonomic paraganglia of the neuroendocrine system, paragangliomas are rare neoplasms that are derived from the embryonic neural crest. Primary paragangliomas of the lung are exceedingly rare, with little known about their origin. Here we present a 47-year-old female presenting in 2021, one year after a COVID-19 infection, with symptoms of tachycardia, shortness of breath, and palpitations which she associated with presumed long COVID-19. An imaging workup noted a 1.5 cm nodule in the lingula of the left lung. She then had surgical resection of the nodule, which was found to be a primary lung paraganglioma. A follow-up dotatate positron emission tomography (PET) CT noted no residual disease, and genetic testing was negative for known mutations. This case demonstrates the need for close monitoring with follow-up for incidental findings in order to provide a timely and accurate diagnosis in accordance with guideline criteria.}, } @article {pmid35784959, year = {2022}, author = {Khasnavis, S and Habib, M and Kaawar, F and Lee, S and Capo, A and Atoot, A}, title = {New Perspectives on Long COVID Syndrome: The Development of Unusually Delayed and Recurring Pericarditis After a Primary SARS-CoV-2 Infection.}, journal = {Cureus}, volume = {14}, number = {6}, pages = {e25559}, pmid = {35784959}, issn = {2168-8184}, abstract = {Since the start of the COVID-19 pandemic in early 2020, pericarditis has been identified as a COVID-19 complication. We report a case where the development of pericarditis was unusually delayed after the initial COVID infection. The reported onset of pericarditis and pericardial effusion is anywhere from a few days to a few months after infection. Our case surmises that a latent complication of COVID-19 can manifest more than one year after the initial infection. A forty-three-year-old male with a past medical history of SARS-CoV-2 infection in September 2020 presented in September 2021 and January 2022 with recurrent sharp chest pain and shortness of breath. During both admissions, he was diagnosed with acute pericarditis, and his workup was significant for elevations in D-dimer and CRP as well as pericardial and pleural effusions. Recurring pericardial symptoms and persistent elevations in D-dimer and CRP point toward a COVID etiology, particularly in the absence of other factors associated with pericarditis. Our case highlights the importance of recognizing this latent complication one year after the initial infection and how the symptoms can persist beyond the one-year period.}, } @article {pmid35783877, year = {2022}, author = {Kumar, GS and Vadgaonkar, A and Purunaik, S and Shelatkar, R and Vaidya, VG and Ganu, G and Vadgaonkar, A and Joshi, S}, title = {Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e25467}, pmid = {35783877}, issn = {2168-8184}, abstract = {Introduction In the present study, the combination of two tablets, one with Aspirin and Promethazine and the other with vitamin D3, C, and B3 along with zinc and selenium supplementation was proposed as an intervention (APMV2020). The ingredients in the formulation represent a precise, tailored therapy for the symptoms of COVID-19, combined with natural constituents to help the body itself build immunity to recover from infection. The present study was conducted to clinically validate the safety and efficacy of the APMV2020 tablets. Trial design The present trial is a randomized, multicentric, controlled clinical trial involving 260 mild to moderate COVID-19 patients. The treatment duration was of 10 days. Methodology The subjects were randomized to receive either the control intervention (clinical management protocol for COVID-19 advocated by the Indian Council of Medical Research (ICMR) or the test intervention (treatment with APMV2020 tablets along with the standard control treatment. The assessment days were baseline, days five and 10. Results APMV2020 significantly (<0.05) improved symptoms of COVID-19 like cough, myalgia, headache, and anosmia as compared to the control group. APMV2020 treatment also reduced inflammatory markers like lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP). Conclusion APMV2020 can prove as a good candidate to be integrated into the COVID-19 management protocol. As it can offer speedy clinical recovery to reduce the burden on healthcare infrastructure, second, the combination shows significant anti-inflammatory potential to improve prognosis, and lastly, the immunomodulatory properties offer long-term protection that can help in combating long COVID symptoms and complications.}, } @article {pmid35783627, year = {2022}, author = {Twele, F and Ten Hagen, NA and Meller, S and Schulz, C and Osterhaus, A and Jendrny, P and Ebbers, H and Pink, I and Drick, N and Welte, T and Schalke, E and Volk, HA}, title = {Detection of Post-COVID-19 Patients Using Medical Scent Detection Dogs-A Pilot Study.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {877259}, pmid = {35783627}, issn = {2296-858X}, abstract = {There is a growing number of COVID-19 patients experiencing long-term symptoms months after their acute SARS-CoV-2 infection. Previous research proved dogs' ability to detect acute SARS-CoV-2 infections, but has not yet shown if dogs also indicate samples of patients with post-COVID-19 condition (Long COVID). Nine dogs, previously trained to detect samples of acute COVID-19 patients, were confronted with samples of Long COVID patients in two testing scenarios. In test scenario I (samples of acute COVID-19 vs. Long COVID) dogs achieved a mean sensitivity (for acute COVID-19) of 86.7% (95%CI: 75.4-98.0%) and a specificity of 95.8% (95%CI: 92.5-99.0%). When dogs were confronted with Long COVID and negative control samples in scenario IIa, dogs achieved a mean sensitivity (for Long COVID) of 94.4 (95%CI: 70.5-100.0%) and a specificity of 96.1% (95%CI: 87.6-100.0%). In comparison, when acute SARS-CoV-2 positive samples and negative control samples were comparatively presented (scenario IIb), a mean sensitivity of 86.9 (95%CI: 55.7-100.0%) and a specificity of 88.1% (95%CI: 82.7-93.6%) was attained. This pilot study supports the hypothesis of volatile organic compounds (VOCs) being long-term present after the initial infection in post-COVID-19 patients. Detection dogs, trained with samples of acute COVID-19 patients, also identified samples of Long COVID patients with a high sensitivity when presented next to samples of healthy individuals. This data may be used for further studies evaluating the pathophysiology underlying Long COVID and the composition of specific VOC-patterns released by SARS-CoV-2 infected patients throughout the course of this complex disease.}, } @article {pmid35782298, year = {2022}, author = {Wilson, C}, title = {Long covid risk with omicron may be half that of delta.}, journal = {New scientist (1971)}, volume = {254}, number = {3392}, pages = {12}, doi = {10.1016/S0262-4079(22)01099-5}, pmid = {35782298}, issn = {0262-4079}, } @article {pmid35781635, year = {2022}, author = {Asadi-Pooya, AA and Nemati, H and Shahisavandi, M and Akbari, A and Emami, A and Lotfi, M and Rostamihosseinkhani, M and Barzegar, Z and Kabiri, M and Zeraatpisheh, Z and Farjoud-Kouhanjani, M and Jafari, A and Sasannia, S and Ashrafi, S and Nazeri, M and Nasiri, S}, title = {Correction to: Long COVID in children and adolescents.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12519-022-00588-4}, pmid = {35781635}, issn = {1867-0687}, } @article {pmid35780756, year = {2022}, author = {Bertuccelli, M and Ciringione, L and Rubega, M and Bisiacchi, P and Masiero, S and Del Felice, A}, title = {Cognitive impairment in people with previous COVID-19 infection: A scoping review.}, journal = {Cortex; a journal devoted to the study of the nervous system and behavior}, volume = {154}, number = {}, pages = {212-230}, pmid = {35780756}, issn = {1973-8102}, mesh = {*COVID-19 ; *Cognitive Dysfunction ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 is a worldwide public health issue. Almost 2 years into the pandemic, the persistence of symptoms after the acute phase is a well-recognized phenomenon. We conducted a scoping review to map cognitive domain impairments, their frequency, and associated psycho-affective disorders in people with a previous COVID-19 infection. We searched PubMed/MEDLINE, Scopus, and PsycInfo to identify relevant reports published between December 1, 2019 and February 21, 2022. We followed the PRISMA (Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses) extension for scoping review guidelines. Three independent reviewers selected and charted 25 records out of 922. Memory, attention, and executive functions appeared to be the most affected domains. Delayed recall and learning were the most impaired domains of memory. Among the executive functions, abstraction, inhibition, set shifting, and sustained and selective attention were most commonly impaired. Language and visuo-spatial abilities were rarely affected, although this finding might be biased by the scarcity of reports. Neurological and respiratory conditions were often reported in association with cognitive deficits. Results on psycho-affective conditions were inconclusive due to the low frequency of reported data. Admission to an intensive care unit is not related to cognitive deficits. This review highlighted a potential effect of a previous post-COVID-19 infection on a pattern of memory, attention, and executive functions impairments. These findings need to be confirmed on larger cohorts with comprehensive neuropsychological batteries and correlated to neurophysiological and neurobiological substrates.}, } @article {pmid35778936, year = {2022}, author = {Manhas, KP and O'Connell, P and Krysa, J and Henderson, I and Ho, C and Papathanassoglou, E}, title = {Development of a Novel Care Rehabilitation Pathway for Post-COVID Conditions (Long COVID) in a Provincial Health System in Alberta, Canada.}, journal = {Physical therapy}, volume = {102}, number = {9}, pages = {}, doi = {10.1093/ptj/pzac090}, pmid = {35778936}, issn = {1538-6724}, support = {//Canadian Institute of Health Research/ ; }, mesh = {Alberta ; *COVID-19/complications ; Canada ; Critical Pathways ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The purpose of this study was to describe the development and composition of a codesigned, multidisciplinary, integrated, systematic rehabilitation framework for post-COVID conditions (PCC) that spans the care continuum to streamline and standardize rehabilitation services to support persons with PCC in Alberta, Canada.

METHODS: A collaborative, consensus-based approach was used involving 2 iterative provincial taskforces in a Canadian provincial health system. The first taskforce (59 multidisciplinary stakeholders) sought to clarify the requisite facets of a sustainable, provincially coordinated rehabilitation approach for post-COVID rehabilitation needs based on available research evidence. The second taskforce (129 multidisciplinary stakeholders) translated that strategy and criteria into an operational framework for provincial implementation. Both taskforces sought to align with operational realities of the provincial health system.

RESULTS: The summation of this collaborative consensus approach resulted in the Provincial Post COVID-19 Rehabilitation Response Framework (PCRF). The PCRF includes 3 care pathways across the care continuum specifically targeting in-hospital care, continuing care, and community-based care with 3 key elements: (1) the use of specific symptom screening and assessment tools to systematically identify PCC symptoms and functional impairments, (2) pathways to determine patients' rehabilitation trajectory and guide their transition between care settings, and (3) self-management and education resources for patients and providers.

CONCLUSION: The PCRF aligns with international mandates for novel, codesigned, multidisciplinary approaches to systematically address PCC and its myriad manifestations across the care continuum. The PCRF allows for local adaptation and highlights equity considerations, allowing for further spread and scale provincially, nationally, and internationally.

IMPACT: The PCRF is a framework for health systems to ensure consistent identification, assessment, and management of the rehabilitation needs of postacute and chronic PCC. Rehabilitation providers and health systems can build from the PCRF for their local communities to reduce unmet needs and advance the standardization of access to rehabilitation services for persons with PCC.}, } @article {pmid35777859, year = {2024}, author = {Gustavson, AM and Eaton, TL and Schapira, RM and Iwashyna, TJ and Adly, M and Purnell, A}, title = {Approaches to long COVID care: the Veterans Health Administration experience in 2021.}, journal = {BMJ military health}, volume = {170}, number = {2}, pages = {179-180}, doi = {10.1136/military-2022-002185}, pmid = {35777859}, issn = {2633-3775}, support = {K12 HS026379/HS/AHRQ HHS/United States ; }, mesh = {Humans ; Veterans Health ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Mental Health Services ; *Veterans ; }, } @article {pmid35776557, year = {2022}, author = {Mendes, A}, title = {Adjuncts to treatments for long COVID.}, journal = {British journal of community nursing}, volume = {27}, number = {7}, pages = {318-319}, doi = {10.12968/bjcn.2022.27.7.318}, pmid = {35776557}, issn = {1462-4753}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35776165, year = {2023}, author = {Tenforde, MW and Devine, OJ and Reese, HE and Silk, BJ and Iuliano, AD and Threlkel, R and Vu, QM and Plumb, ID and Cadwell, BL and Rose, C and Steele, MK and Briggs-Hagen, M and Ayoubkhani, D and Pawelek, P and Nafilyan, V and Saydah, SH and Bertolli, J}, title = {Point Prevalence Estimates of Activity-Limiting Long-term Symptoms Among United States Adults ≥1 Month After Reported Severe Acute Respiratory Syndrome Coronavirus 2 Infection, 1 November 2021.}, journal = {The Journal of infectious diseases}, volume = {227}, number = {7}, pages = {855-863}, doi = {10.1093/infdis/jiac281}, pmid = {35776165}, issn = {1537-6613}, support = {/CC/CDC HHS/United States ; }, mesh = {Male ; Female ; Adult ; Humans ; United States/epidemiology ; *COVID-19/epidemiology ; SARS-CoV-2 ; Prevalence ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021.

METHODS: We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration.

RESULTS: On 1 November 2021, at least 3.0-5.0 million US adults, or 1.2%-1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month's duration. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%-3.8%.

CONCLUSIONS: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.}, } @article {pmid35776071, year = {2022}, author = {Langnickel, L and Darms, J and Heldt, K and Ducks, D and Fluck, J}, title = {Continuous development of the semantic search engine preVIEW: from COVID-19 to long COVID.}, journal = {Database : the journal of biological databases and curation}, volume = {2022}, number = {}, pages = {}, pmid = {35776071}, issn = {1758-0463}, mesh = {*COVID-19/complications/epidemiology ; Humans ; SARS-CoV-2 ; *Search Engine ; Semantics ; Post-Acute COVID-19 Syndrome ; }, abstract = {preVIEW is a freely available semantic search engine for Coronavirus disease (COVID-19)-related preprint publications. Currently, it contains >43 800 documents indexed with >4000 semantic concepts, annotated automatically. During the last 2 years, the dynamic situation of the corona crisis has demanded dynamic development. Whereas new semantic concepts have been added over time-such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest-the service has been also extended with several features improving the usability and user friendliness. Most importantly, the user is now able to give feedback on detected semantic concepts, i.e. a user can mark annotations as true positives or false positives. In addition, we expanded our methods to construct search queries. The presented version of preVIEW also includes links to the peer-reviewed journal articles, if available. With the described system, we participated in the BioCreative VII interactive text-mining track and retrieved promising user-in-the-loop feedback. Additionally, as the occurrence of long-term symptoms after an infection with the virus SARS-CoV-2-called long COVID-is getting more and more attention, we have recently developed and incorporated a long COVID classifier based on state-of-the-art methods and manually curated data by experts. The service is freely accessible under https://preview.zbmed.de.}, } @article {pmid35773859, year = {2022}, author = {Kulenovic, A and Lagumdzija-Kulenovic, A}, title = {Using Logistic Regression to Predict Long COVID Conditions in Chronic Patients.}, journal = {Studies in health technology and informatics}, volume = {295}, number = {}, pages = {265-268}, doi = {10.3233/SHTI220713}, pmid = {35773859}, issn = {1879-8365}, mesh = {*COVID-19/complications ; Electronic Health Records ; Humans ; Logistic Models ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Chronic diseases pose significant challenges to patients and healthcare systems, and the COVID-19 pandemic has further deteriorated that situation. This paper presents a method for predicting selected long COVID conditions in chronic and multimorbidity patients. It produces a logistic regression model for each long COVID condition by examining electronic medical records (EMRs) of COVID-19 patients and taking their chronic conditions as predictors. The models were developed and tested using the Jumpstart EMR database, provided in the COVID-19 Research Environment of Hopkins University, containing about 250,000 EMRs of the outpatient and ambulatory COVID-19 patients across the US. They are illustrated by predictions of 20 prevalent acute and chronic long-COVID conditions in patients diagnosed with frequent pre-COVID chronic diseases. These models can aid in investigating long COVID impacts on various chronic patients, finding their underlying pathophysiology, and establishing guidelines for their treatment and prevention.}, } @article {pmid35772782, year = {2023}, author = {Gambardella, J and Kansakar, U and Sardu, C and Messina, V and Jankauskas, SS and Marfella, R and Maggi, P and Wang, X and Mone, P and Paolisso, G and Sorriento, D and Santulli, G}, title = {Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {384}, number = {1}, pages = {109-115}, pmid = {35772782}, issn = {1521-0103}, support = {R01 DK123259/DK/NIDDK NIH HHS/United States ; R01 DK033823/DK/NIDDK NIH HHS/United States ; R01 HL159062/HL/NHLBI NIH HHS/United States ; R01 HL146691/HL/NHLBI NIH HHS/United States ; T32 HL144456/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *COVID-19/complications ; Endothelial Cells ; *MicroRNAs/genetics/metabolism ; *Post-Acute COVID-19 Syndrome/genetics/metabolism ; SARS-CoV-2 ; *Thrombosis/genetics/metabolism/virology ; *Exosomes/metabolism ; }, abstract = {We hypothesized that exosomal microRNAs could be implied in the pathogenesis of thromboembolic complications in coronavirus disease 2019 (COVID-19). We isolated circulating exosomes from patients with COVID-19, and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for the internalization of the "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), including angiotensin converting enzyme 2, transmembrane protease serine 2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared with cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19. SIGNIFICANCE STATEMENT: This work demonstrates for the first time that two specific microRNAs (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. These findings are especially relevant to the general audience when considering the emerging prominence of post-acute sequelae of COVID-19 systemic manifestations known as Long COVID.}, } @article {pmid35772216, year = {2022}, author = {Krishna, BA and Lim, EY and Mactavous, L and , and Lyons, PA and Doffinger, R and Bradley, JR and Smith, KGC and Sinclair, J and Matheson, NJ and Lehner, PJ and Wills, MR and Sithole, N}, title = {Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104129}, pmid = {35772216}, issn = {2352-3964}, support = {MR/V028448/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; MR/V011561/1/MRC_/Medical Research Council/United Kingdom ; MR/T032413/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/S00081X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antibodies, Viral ; *COVID-19/complications ; Humans ; Interleukin-2 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative.

METHODS: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients.

FINDINGS: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses.

INTERPRETATION: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID.

FUNDING: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).}, } @article {pmid35768516, year = {2022}, author = {Minton, K}, title = {Mechanistic insights into Long COVID in hamsters.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {8}, pages = {463}, pmid = {35768516}, issn = {1474-1741}, mesh = {Animals ; *COVID-19/complications ; Cricetinae ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35768406, year = {2022}, author = {Hawke, LD and Nguyen, ATP and Ski, CF and Thompson, DR and Ma, C and Castle, D}, title = {Interventions for mental health, cognition, and psychological wellbeing in long COVID: a systematic review of registered trials.}, journal = {Psychological medicine}, volume = {52}, number = {13}, pages = {2426-2440}, pmid = {35768406}, issn = {1469-8978}, support = {WI1-179893//CIHR/Canada ; }, mesh = {Humans ; *Mental Health ; *COVID-19 ; Bias ; Post-Acute COVID-19 Syndrome ; Cognition ; }, abstract = {BACKGROUND: Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as 'long COVID'. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID.

METHODS: Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted.

RESULTS: Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes.

CONCLUSIONS: While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.}, } @article {pmid35768219, year = {2022}, author = {Aikawa, T and Ogino, J and Oyama-Manabe, N and Funayama, N}, title = {Vasospastic Angina: A Cause of Post-acute COVID-19 Syndrome.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {61}, number = {17}, pages = {2693-2695}, pmid = {35768219}, issn = {1349-7235}, mesh = {Angina Pectoris/complications ; *Angina Pectoris, Variant/complications ; *COVID-19/complications ; *Coronary Vasospasm/etiology ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35768007, year = {2022}, author = {Kao, J and Frankland, PW}, title = {COVID fog demystified.}, journal = {Cell}, volume = {185}, number = {14}, pages = {2391-2393}, pmid = {35768007}, issn = {1097-4172}, mesh = {*COVID-19/complications ; *Cognitive Dysfunction ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as "COVID fog." New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.}, } @article {pmid35768006, year = {2022}, author = {Fernández-Castañeda, A and Lu, P and Geraghty, AC and Song, E and Lee, MH and Wood, J and O'Dea, MR and Dutton, S and Shamardani, K and Nwangwu, K and Mancusi, R and Yalçın, B and Taylor, KR and Acosta-Alvarez, L and Malacon, K and Keough, MB and Ni, L and Woo, PJ and Contreras-Esquivel, D and Toland, AMS and Gehlhausen, JR and Klein, J and Takahashi, T and Silva, J and Israelow, B and Lucas, C and Mao, T and Peña-Hernández, MA and Tabachnikova, A and Homer, RJ and Tabacof, L and Tosto-Mancuso, J and Breyman, E and Kontorovich, A and McCarthy, D and Quezado, M and Vogel, H and Hefti, MM and Perl, DP and Liddelow, S and Folkerth, R and Putrino, D and Nath, A and Iwasaki, A and Monje, M}, title = {Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.}, journal = {Cell}, volume = {185}, number = {14}, pages = {2452-2468.e16}, pmid = {35768006}, issn = {1097-4172}, support = {R01 EY033353/EY/NEI NIH HHS/United States ; T32 GM145402/GM/NIGMS NIH HHS/United States ; DP1 NS111132/NS/NINDS NIH HHS/United States ; R01 NS092597/NS/NINDS NIH HHS/United States ; K23 NS109284/NS/NINDS NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; /CRUK_/Cancer Research UK/United Kingdom ; T32 GM007365/GM/NIGMS NIH HHS/United States ; T32 AI007019/AI/NIAID NIH HHS/United States ; T32 CA009302/CA/NCI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; K08 AI163493/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *COVID-19 ; Humans ; *Influenza, Human/pathology ; Mice ; Microglia/pathology ; Myelin Sheath ; *Neoplasms/pathology ; SARS-CoV-2 ; }, abstract = {COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.}, } @article {pmid35766728, year = {2022}, author = {Pichardo-Rodríguez, R and Bracamonte-Hernández, JJ and Ramírez-Meyhuay, DC and Arquinigo-Lavado, IR and Peña-Oscuvilca, W and Saavedra-Velasco, M and Ruiz-Franco, O}, title = {Concurrence between Guillain-Barré syndrome and immune thrombocytopenic purpura possibly induced by long COVID-19.}, journal = {Revista peruana de medicina experimental y salud publica}, volume = {39}, number = {1}, pages = {111-114}, pmid = {35766728}, issn = {1726-4642}, mesh = {*COVID-19/complications ; *Guillain-Barre Syndrome/complications/therapy ; Humans ; Male ; *Purpura, Thrombocytopenic, Idiopathic/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {During acute SARS-CoV-2 infection, there is persistent deregulation of the immune system that can last up to 8 months after the acute condition is controlled. This, added to other factors, is possibly associated with an increased risk of the appearance and concurrence of autoimmune diseases. The simultaneous occurrence of GBS and ITP has been rarely reported in the literature, and GBS is rarely associated with another autoimmune disease. We present the case of a man who, one month after his recovery from acute moderate COVID-19, presented concurrent GBS and ITP with an adequate response to treatment.}, } @article {pmid35766219, year = {2023}, author = {Shankar, R and Perera, B and Roy, A and Courtenay, K and Laugharne, R and Sivan, M}, title = {Post-COVID syndrome and adults with intellectual disability: another vulnerable population forgotten?.}, journal = {The British journal of psychiatry : the journal of mental science}, volume = {222}, number = {1}, pages = {1-3}, doi = {10.1192/bjp.2022.89}, pmid = {35766219}, issn = {1472-1465}, mesh = {Child ; Adult ; Humans ; *Intellectual Disability/epidemiology ; Vulnerable Populations ; *COVID-19 ; Developmental Disabilities ; Post-Acute COVID-19 Syndrome ; }, abstract = {An area of interest presently is the lingering symptoms after COVID-19, i.e. post-COVID-19 syndrome (PCS). Specifics of diagnosis and management of PCS are emerging. However, vulnerable populations such as those with intellectual disabilities, who were disproportionately affected by the pandemic, risk being 'left behind' from these considerations.}, } @article {pmid35765623, year = {2022}, author = {}, title = {[Not Available].}, journal = {Padiatrie und Padologie}, volume = {57}, number = {3}, pages = {120-124}, doi = {10.1007/s00608-022-00983-0}, pmid = {35765623}, issn = {0030-9338}, } @article {pmid35765566, year = {2022}, author = {Badran, BW and Huffman, SM and Dancy, M and Austelle, CW and Bikson, M and Kautz, SA and George, MS}, title = {A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35765566}, issn = {2693-5015}, support = {IK6 RX003075/RX/RRD VA/United States ; U54 GM104941/GM/NIGMS NIH HHS/United States ; }, abstract = {Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered onClinicalTrials.gov under the identifier: NCT04638673. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.}, } @article {pmid35765080, year = {2022}, author = {Bothou, C and Saleh, L and von Eckardstein, A and Beuschlein, F and Nowak, A}, title = {COVID-19 in Fabry disease: a reference center prospective study.}, journal = {Orphanet journal of rare diseases}, volume = {17}, number = {1}, pages = {250}, pmid = {35765080}, issn = {1750-1172}, mesh = {*COVID-19/complications ; *Fabry Disease/genetics ; Female ; Humans ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: During the coronavirus disease-19 (COVID-19) pandemic, vulnerable populations must be identified to prevent increased mortality. Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to chronic kidney disease (CKD), cardiomyopathy, pneumonopathy and premature strokes. Little is known whether SARS-CoV-2 infection bears a particular risk for FD patients.

METHODS: During pandemic (02.2020-03.2021) we have regularly followed 104 unvaccinated FD patients. In 61/104, titre of serum antibodies against SARS-CoV-2 were measured and SARS-CoV-2 PCR test was performed in symptomatic patients or in case of positivity of other family members. The symptoms and duration of COVID-19 were reported by the patients or the treating physician.

RESULTS: No deaths or intensive care unit hospitalizations occurred. 13/104 (12.5%) were diagnosed with SARS-CoV-2 infection (16.7% (4/24) men 12.2% (6/49) women of classic phenotype, 25% (3/12) of the men and 0% (0/8) of the women of later- onset phenotype). Of those, 2/13 (15.4%) patients-both kidney transplant recipients-developed severe COVID-19, were hospitalized, and required a high-flow oxygen mask. The rest either developed mild COVID-19 manifestations (8/13, 61.5%) or were asymptomatic (3/13, 23.1%). 2/13 (15.4%) of the patients experienced Fabry pain crisis and 3/13 (23.1%) long COVID-19 like symptoms.

CONCLUSIONS: Similar to the general population, in FD patients the risk for severe COVID-19 seems to be driven by the immune system rather than by FD itself. Immunosuppression in kidney transplant recipients represented the highest risk in this population.}, } @article {pmid35764955, year = {2022}, author = {Cash, A and Kaufman, DL}, title = {Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {295}, pmid = {35764955}, issn = {1479-5876}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/complications/drug therapy ; Female ; Humans ; Male ; Mental Fatigue/drug therapy/virology ; Middle Aged ; *Oxaloacetic Acid/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue.

METHODS: ME/CFS and Long-COVID patients were enrolled in an open label dose escalating "Proof of Concept" non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of the ME/CFS patients were women, average age was 47 and length of ME/CFS from diagnosis was 8.9 years. The Long-COVID patients were a random group that responded to social media advertising (Face Book) with symptoms for at least 6 months. ME/CFS patients were given separate doses of 500 mg BID (N = 23), 1,000 mg BID (N = 29) and 1000 mg TID (N = 24) AEO for six weeks. Long COVID patients were given 500 mg AEO BID (N = 22) and 1000 mg AEO (N = 21), again over a six-week period. The main outcome measure was to compare baseline scoring with results at 6 weeks with the Chalder Fatigue Score (Likert Scoring) versus historical placebo. The hypothesis being tested was formulated prior to data collection.

RESULTS: 76 ME/CFS patients (73.7% women, median age of 47) showed an average reduction in fatigue at 6 weeks as measured by the "Chalder Fatigue Questionnaire" of 22.5% to 27.9% from baseline (P < 0.005) (Likert scoring). Both physical and mental fatigue were significantly improved over baseline and historical placebo. Fatigue amelioration in ME/CFS patients increased in a dose dependent manner from 21.7% for 500 mg BID to 27.6% for 1000 mg Oxaloacetate BID to 33.3% for 1000 mg TID. Long COVID patients' fatigue was significantly reduced by up to 46.8% in 6-weeks.

CONCLUSIONS: Significant reductions in physical and metal fatigue for ME/CFS and Long-COVID patients were seen after 6 weeks of treatment. As there has been little progress in providing fatigue relief for the millions of ME/CFS and Long COVID patients, anhydrous enol oxaloacetate may bridge this important medical need. Further study of oxaloacetate supplementation for the treatment of ME/CFS and Long COVID is warranted. Trial Registration https://clinicaltrials.gov/ct2/show/NCT04592354 Registered October 19, 2020. 1,000 mg BID Normalized Fatigue Data for Baseline, 2-weeks and 6-weeks evaluated by 3 Validated Fatigue Scoring Questionnaires.}, } @article {pmid35764621, year = {2022}, author = {Thompson, EJ and Williams, DM and Walker, AJ and Mitchell, RE and Niedzwiedz, CL and Yang, TC and Huggins, CF and Kwong, ASF and Silverwood, RJ and Di Gessa, G and Bowyer, RCE and Northstone, K and Hou, B and Green, MJ and Dodgeon, B and Doores, KJ and Duncan, EL and Williams, FMK and , and Steptoe, A and Porteous, DJ and McEachan, RRC and Tomlinson, L and Goldacre, B and Patalay, P and Ploubidis, GB and Katikireddi, SV and Tilling, K and Rentsch, CT and Timpson, NJ and Chaturvedi, N and Steves, CJ}, title = {Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3528}, pmid = {35764621}, issn = {2041-1723}, support = {COV-LT-0009/DH_/Department of Health/United Kingdom ; 217065/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; 104036/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_15018/MRC_/Medical Research Council/United Kingdom ; WT101597MA/WT_/Wellcome Trust/United Kingdom ; 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MR/P023444/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_19009/MRC_/Medical Research Council/United Kingdom ; CZD/16/6/CSO_/Chief Scientist Office/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_UU_00011/1/MRC_/Medical Research Council/United Kingdom ; C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; 221574/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; CS/16/4/32482/BHF_/British Heart Foundation/United Kingdom ; MC_UU_00019/1/MRC_/Medical Research Council/United Kingdom ; MR/R024774/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/2/MRC_/Medical Research Council/United Kingdom ; MR/V015737//MRC_/Medical Research Council/United Kingdom ; NIHR200166/DH_/Department of Health/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; G9815508/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 216767/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MC_UU_00011/3/MRC_/Medical Research Council/United Kingdom ; MR/N024397/1/MRC_/Medical Research Council/United Kingdom ; 204813/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; SPHSU17/CSO_/Chief Scientist Office/United Kingdom ; WT212904/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; *Electronic Health Records ; Female ; Humans ; Longitudinal Studies ; Risk Factors ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.}, } @article {pmid35763985, year = {2022}, author = {Rubega, M and Ciringione, L and Bertuccelli, M and Paramento, M and Sparacino, G and Vianello, A and Masiero, S and Vallesi, A and Formaggio, E and Del Felice, A}, title = {High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {140}, number = {}, pages = {126-135}, pmid = {35763985}, issn = {1872-8952}, mesh = {*COVID-19 ; Cognition ; Electroencephalography ; Follow-Up Studies ; Humans ; Intensive Care Units ; Quality of Life ; Sleep/physiology ; }, abstract = {OBJECTIVE: To disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19.

METHODS: People discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation.

RESULTS: We enrolled 33 participants (17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators.

CONCLUSIONS: Our results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors - especially in nonICU participants - after 12 months from discharge.

SIGNIFICANCE: These findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.}, } @article {pmid35763279, year = {2022}, author = {De Luca, P and Di Stadio, A and Colacurcio, V and Marra, P and Scarpa, A and Ricciardiello, F and Cassandro, C and Camaioni, A and Cassandro, E}, title = {Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence.}, journal = {Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale}, volume = {42}, number = {Suppl. 1}, pages = {S87-S93}, pmid = {35763279}, issn = {1827-675X}, mesh = {*COVID-19/complications ; Hearing Disorders/diagnosis/virology ; Humans ; *Olfaction Disorders/diagnosis/virology ; SARS-CoV-2 ; *Taste Disorders/diagnosis/virology ; Vertigo/diagnosis/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID".

METHODS: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2.

RESULTS: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021.

CONCLUSIONS: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.}, } @article {pmid35760447, year = {2022}, author = {Hylton, H and Long, A and Francis, C and Taylor, RR and Ricketts, WM and Singh, R and Pfeffer, PE}, title = {Real-world use of the Breathing Pattern Assessment Tool in assessment of breathlessness post-COVID-19.}, journal = {Clinical medicine (London, England)}, volume = {22}, number = {4}, pages = {376-379}, pmid = {35760447}, issn = {1473-4893}, abstract = {INTRODUCTION: Breathing pattern disorders (BPDs) are a common cause of chronic breathlessness, including after acute respiratory illnesses such as COVID pneumonia. BPD is however underdiagnosed, partly as a result of difficulty in clinically assessing breathing pattern. The Breathing Pattern Assessment Tool (BPAT) has been validated for use in diagnosing BPD in patients with asthma but to date has not been validated in other diseases.

METHODS: Patients undergoing face-to-face review in a post-COVID clinic were assessed by a respiratory physician and specialist respiratory physiotherapist. Assessment included a Dyspnoea-12 (D12) questionnaire to assess breathlessness, physiotherapist assessment of breathing pattern including manual assessment of respiratory motion, and BPAT assessment. The sensitivity and specificity of BPAT for diagnosis of BPD in post-COVID patients was assessed.

RESULTS: BPAT had a sensitivity of 89.5% and specificity of 78.3% for diagnosing BPD in post-COVID breathlessness. Patients with a BPAT score above the diagnostic cut-off had higher levels of breathlessness than those with lower BPAT scores (D12 score mean average 19.4 vs 13.2).

CONCLUSION: BPAT has high sensitivity and moderate specificity for BPD in patients with long COVID. This would support its use as a screening test in clinic, and as a diagnostic tool for large cohort studies.}, } @article {pmid35757700, year = {2022}, author = {Wiech, M and Chroscicki, P and Swatler, J and Stepnik, D and De Biasi, S and Hampel, M and Brewinska-Olchowik, M and Maliszewska, A and Sklinda, K and Durlik, M and Wierzba, W and Cossarizza, A and Piwocka, K}, title = {Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {886431}, pmid = {35757700}, issn = {1664-3224}, mesh = {CD4-Positive T-Lymphocytes ; *COVID-19/complications ; Fatigue ; Granzymes ; Humans ; Inflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given the scale of the worldwide infections, the long-term recovery and the integrative health-care in the nearest future, it is critical to understand the cellular and molecular mechanisms as well as possible predictors of the longitudinal post-COVID-19 responses in convalescent individuals. The immune system and T cell alterations are proposed as drivers of post-acute COVID syndrome. However, despite the number of studies on COVID-19, many of them addressed only the severe convalescents or the short-term responses. Here, we performed longitudinal studies of mild, moderate and severe COVID-19-convalescent patients, at two time points (3 and 6 months from the infection), to assess the dynamics of T cells immune landscape, integrated with patients-reported symptoms. We show that alterations among T cell subsets exhibit different, severity- and time-dependent dynamics, that in severe convalescents result in a polarization towards an exhausted/senescent state of CD4+ and CD8+ T cells and perturbances in CD4+ Tregs. In particular, CD8+ T cells exhibit a high proportion of CD57+ terminal effector cells, together with significant decrease of naïve cell population, augmented granzyme B and IFN-γ production and unresolved inflammation 6 months after infection. Mild convalescents showed increased naïve, and decreased central memory and effector memory CD4+ Treg subsets. Patients from all severity groups can be predisposed to the long COVID symptoms, and fatigue and cognitive dysfunctions are not necessarily related to exhausted/senescent state and T cell dysfunctions, as well as unresolved inflammation that was found only in severe convalescents. In conclusion, the post-COVID-19 functional remodeling of T cells could be seen as a two-step process, leading to distinct convalescent immune states at 6 months after infection. Our data imply that attenuation of the functional polarization together with blocking granzyme B and IFN-γ in CD8+ cells might influence post-COVID alterations in severe convalescents. However, either the search for long COVID predictors or any treatment to prevent PACS and further complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe COVID-19.}, } @article {pmid35756854, year = {2022}, author = {Kluge, HHP and Muscat, NA and , and Mishra, S and Nielsen, S and Tille, F and Pfeifer, D and Covid Europe, L and Sivan, M}, title = {Call for action: Health services in the European region must adopt integrated care models to manage Post-Covid-19 Condition.}, journal = {The Lancet regional health. Europe}, volume = {18}, number = {}, pages = {100435}, pmid = {35756854}, issn = {2666-7762}, support = {001/WHO_/World Health Organization/International ; }, } @article {pmid35755951, year = {2022}, author = {Carter, SJ and Baranauskas, MN and Raglin, JS and Pescosolido, BA and Perry, BL}, title = {Functional Status, Mood State, and Physical Activity Among Women With Post-Acute COVID-19 Syndrome.}, journal = {International journal of public health}, volume = {67}, number = {}, pages = {1604589}, pmid = {35755951}, issn = {1661-8564}, support = {UL1 TR002529/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; *COVID-19/complications/epidemiology ; Exercise ; Female ; Functional Status ; Humans ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objectives: While organ-specific pathophysiology has been well-described in SARS-CoV-2 infection, less is known about the attendant effects on functional status, mood state and leisure-time physical activity (PA) in post-acute COVID-19 syndrome (PASC). Methods: A case-control design was employed to recruit 32 women (n = 17 SARS-CoV-2; n = 15 controls) matched on age (54 ± 12 years) and body mass index (27 ± 6 kg/m[2]) that did not differ by smoking status or history of cardiopulmonary disease. Participants completed a series of assessments including Profile of Mood States (POMS), Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M), and Godin-Shephard Leisure-Time PA. Results: Significant between-group differences were detected for the POMS total mood disturbance with sub-scale analyses revealing elevated tension, confusion, and lower vigor among SARS-CoV-2 participants (all p-values < 0.05). The number of SARS-CoV-2 symptoms (e.g., loss of taste/smell, muscle aches etc.) were associated (r = 0.620, p = 0.008) with confusion. SARS-CoV-2 participants exhibited poorer functional status (p = 0.008) and reduced leisure-time PA (p = 0.004) compared to controls. Conclusion: The sequela of persistent SARS-CoV-2 symptoms elicit clear disturbances in functional status, mood state, and leisure-time PA among women with PASC. Ongoing symptom presentation affects recovery time-course and PA participation.}, } @article {pmid35755616, year = {2022}, author = {Meißner, T}, title = {[Not Available].}, journal = {Pneumo news}, volume = {14}, number = {3}, pages = {35-36}, doi = {10.1007/s15033-022-2851-z}, pmid = {35755616}, issn = {2199-3866}, } @article {pmid35753836, year = {2022}, author = {Pontali, E and Silva, DR and Marx, FM and Caminero, JA and Centis, R and D'Ambrosio, L and Garcia-Garcia, JM and Muhwa, JC and Tiberi, S and Migliori, GB}, title = {Breathing Back Better! A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs.}, journal = {Archivos de bronconeumologia}, volume = {58}, number = {11}, pages = {754-763}, pmid = {35753836}, issn = {1579-2129}, mesh = {Humans ; *COVID-19 ; *Tuberculosis ; Cost-Benefit Analysis ; Lung ; Post-Acute COVID-19 Syndrome ; }, abstract = {Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation. In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness. Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review.}, } @article {pmid35753603, year = {2022}, author = {Petersen, MS and Kristiansen, MF and Hanusson, KD and Foldbo, BM and Danielsen, ME and Á Steig, B and Gaini, S and Strøm, M and Weihe, P}, title = {Prevalence of long COVID in a national cohort: longitudinal measures from disease onset until 8 months' follow-up.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {122}, number = {}, pages = {437-441}, pmid = {35753603}, issn = {1878-3511}, mesh = {*COVID-19/complications/epidemiology ; COVID-19 Testing ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Prevalence ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Persistence of COVID-19 symptoms in nonhospitalized individuals beyond a few months has not been well characterized. In this longitudinal study from the Faroe Islands, we present prevalence of long COVID in mainly nonhospitalized patients who were followed up for up to 8 months.

METHODS: All Faroese individuals with confirmed COVID-19 diagnosis from August to December 2020 were invited to participate in this study (n = 297). Demographic and clinical characteristics and self-reported symptoms were ascertained prospectively using a detailed questionnaire administered at repeated phone interviews.

RESULTS: A total of 226 individuals participated at baseline (226/297, 76% participation rate), of whom 170 participants had more than 3 months follow-up. Of these, 39% (n = 67/170, 95% confidence interval [CI] 32-37%) reported persistent symptoms (median [range] 168 [93-231] days) after the acute phase and 8% (n = 14/170, 95% CI 5-13%) reported severe persistent symptoms. The most prevalent symptoms were fatigue (17%) and smell (17%) and taste (14%) dysfunction. Long COVID was more common in people reporting daily medication use (odds ratio 2.34, 95% CI 1.02-5.37).

CONCLUSION: Our results show that symptoms may take months to resolve, even among nonhospitalized individuals, with a mild illness in the acute phase. Continued monitoring for long COVID is needed to evaluate the added risk of a potential public health concern.}, } @article {pmid35752482, year = {2022}, author = {Ngeow, WC and Tang, L and Ho, JY and Tay, HW and Wong, RCW and Ahmad, MS and Marla, V and Sekar, K}, title = {The Provision of Dental Care to COVID-19 Survivors: A Concise Review.}, journal = {International dental journal}, volume = {72}, number = {4}, pages = {421-435}, pmid = {35752482}, issn = {1875-595X}, mesh = {*COVID-19/complications ; *Dental Care ; Humans ; SARS-CoV-2 ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIMS: It has been reported that there are a certain percentage of COVID-19 patients who recover but suffer from devastating permanent organ damage or failure. Others suffer from long Covid syndrome, with prolonged symptoms that persist more than 12 weeks. However, there is scarcity of literature regarding the provision of dental treatment for these two groups of patients. This manuscript reviews the impact of multi-system involvement on the provision of dental care to these patients.

MATERIALS AND METHODS: A search of literature was done in PubMed-Medline and Scopus databases to review the available literature on COVID-19 impacts on pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, and neurologic systems and respective management in dental clinical settings.

RESULTS: The literature search from PubMed-Medline and Scopus databases resulted in 74 salient articles that contributed to the concise review on COVID-19 effects on pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, and neurologic systems and/or its respective dental management recommendations.

CONCLUSIONS: This concise review covers the management of post COVID-19 patients with pulmonary, cardiovascular, haematologic, renal, gastrointestinal, endocrine, or neurologic system complications.}, } @article {pmid35752194, year = {2022}, author = {Kikkenborg Berg, S and Palm, P and Nygaard, U and Bundgaard, H and Petersen, MNS and Rosenkilde, S and Thorsted, AB and Ersbøll, AK and Thygesen, LC and Nielsen, SD and Vinggaard Christensen, A}, title = {Long COVID symptoms in SARS-CoV-2-positive children aged 0-14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {9}, pages = {614-623}, pmid = {35752194}, issn = {2352-4650}, mesh = {Adolescent ; *COVID-19/complications/epidemiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Denmark/epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: After the acute phase of SARS-CoV-2 infection, children can develop long COVID symptoms. We aimed to investigate the prevalence of long-lasting symptoms, the duration and intensity of symptoms, quality of life, number of sick days and absences from daycare or school, and psychological and social outcomes in children aged 0-14 years who had been infected with SARS-CoV-2 relative to controls with no history of SARS-CoV-2 infection.

METHODS: A nationwide cross-sectional study was conducted including children with a confirmed SARS-CoV-2-positive PCR test (cases) and matched controls from Danish national registers. A survey was sent to mothers (proxy reporting) of children aged 0-14 years who had had a positive SARS-CoV-2 test between Jan 1, 2020, and July 12, 2021, and a control group matched (1:4) by age and sex. The survey included the Pediatric Quality of Life Inventory (PedsQL) and the Children's Somatic Symptoms Inventory-24 (CSSI-24) to capture current overall health and wellbeing, and ancillary questions about the 23 most common long COVID symptoms. Descriptive statistics and logistic regression analysis were used. Clinically relevant differences were defined as those with a Hedges'g score greater than 0·2. This study is registered at ClinicalTrials.gov (NCT04786353).

FINDINGS: Responses to the survey were received from 10 997 (28·8%) of 38 152 cases and 33 016 (22·4%) of 147 212 controls between July 20, 2021, and Sept 15, 2021. Median age was 10·2 years (IQR 6·6-12·8) in cases and 10·6 years (6·9-12·9) in controls. 5267 (48·2%) cases and 15 777 (48·3%) controls were female, and 5658 (51·8%) cases and 16 870 (51·7%) controls were male. Cases had higher odds of reporting at least one symptom lasting more than 2 months than did controls in the 0-3 years age group (478 [40·0%] of 1194 vs 1049 [27·2%] of 3855; OR 1·78 [95% CI 1·55-2·04], p<0·0001), 4-11 years age group (1912 [38·1%] of 5023 vs 6189 [33·7%] of 18 372; 1·23 [1·15-1·31], p<0·0001), and 12-14 years age group (1313 [46·0%] of 2857 vs 4454 [41·3%] of 10 789; 1·21 [1·11-1·32], p<0·0001). Differences in CSSI-24 symptom scores between cases and controls were statistically significant but not clinically relevant. Small clinically relevant differences in PedsQL quality-of-life scores related to emotional functioning were found in favour of cases in the children aged 4-11 years (median score 80·0 [IQR 65·0-95·0]) in cases vs 75·0 [60·0-85·0] in controls; p<0·0001) and 12-14 years (90·0 [70·0-100·0] vs (85·0 [65·0-95·0], p<0·0001). PedsQL social functioning scores were also higher in cases (100·0 [90·0-100·0] than controls (95·0 [80·0-100·0]) in the 12-14 years age group (p<0·0001; Hedges g>0·2).

INTERPRETATION: Compared with controls, children aged 0-14 years who had a SARS-CoV-2 infection had more prevalent long-lasting symptoms. There was a tendency towards better quality-of-life scores related to emotional and social functioning in cases than in controls in older children. The burden of symptoms among children in the control group requires attention. Long COVID must be recognised and multi-disciplinary long COVID clinics for children might be beneficial.

FUNDING: A P Møller and Chastine Mc-Kinney Møller Foundation.}, } @article {pmid35752193, year = {2022}, author = {Rytter, MJH}, title = {Difficult questions about long COVID in children.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {9}, pages = {595-597}, pmid = {35752193}, issn = {2352-4650}, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35750397, year = {2022}, author = {The Lancet Digital Health, }, title = {Big data and long COVID.}, journal = {The Lancet. Digital health}, volume = {4}, number = {7}, pages = {e477}, doi = {10.1016/S2589-7500(22)00113-3}, pmid = {35750397}, issn = {2589-7500}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; SP/14/6/31350/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Big Data ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35747798, year = {2022}, author = {Hajjaji, N and Lepoutre, K and Lakhdar, S and Bécourt, S and Bellier, C and Kaczmarek, E and Broyelle, A and Giscard, S and Lartigau, E}, title = {16 Months Follow Up of Patients' Behavior and Mild COVID-19 Patterns in a Large Cohort of Cancer Patients During the Pandemic.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {901426}, pmid = {35747798}, issn = {2234-943X}, abstract = {Background: Acute severe forms of COVID-19 infection are more likely in cancer patients and growing attention has been given to the persistent symptoms of the disease after severe COVID-19. However, mild illness is the dominant clinical presentation of COVID-19 infection. To investigate patients' behavior and the short- and longer-term pattern of the disease in cancer patients with mild COVID infection, a longitudinal online survey was conducted for 16 months during the pandemic in a large cohort of cancer patients from a French COVID-19 hot spot. An online questionnaire was administered at three time points between the first wave of the pandemic in France and the fourth wave. The questionnaire was completed by 1415 to 2224 patients, which queried patients' demographics, their behavior, and COVID infection patterns. Seventy percent of the patients were female, and 40% had a comorbid condition. More than one-third of the participants had breast cancer, and half were survivors. The rate of infection was 30% during wave 1 and 10% in wave 4; most patients had a mild COVID-19 infection. Twenty-five percent of infected patients during wave 4 did not seek medical advice. At wave 4, 87% of the patients received at least one dose of vaccine. Systematic compliance to shielding measures decreased over time. The short-term pattern of mild COVID changed between wave 1 and wave 4. Twenty-two percent of infected patients experienced persistent signs for more than 6 months with a negative impact on sleep, social behavior, and increased consumption of stress-relieving drugs. Our results showed a high prevalence of long-lasting symptoms in cancer patients with mild COVID-19 infection and inadequate behavior toward the disease and prevention measures among patients.}, } @article {pmid35747600, year = {2022}, author = {Khoja, O and Silva Passadouro, B and Mulvey, M and Delis, I and Astill, S and Tan, AL and Sivan, M}, title = {Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID.}, journal = {Journal of pain research}, volume = {15}, number = {}, pages = {1729-1748}, pmid = {35747600}, issn = {1178-7090}, abstract = {OBJECTIVE: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.

METHODS: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.

RESULTS: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.

CONCLUSION: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.}, } @article {pmid35747313, year = {2022}, author = {Gall, NP and James, S and Kavi, L}, title = {Observational case series of postural tachycardia syndrome (PoTS) in post-COVID-19 patients.}, journal = {The British journal of cardiology}, volume = {29}, number = {1}, pages = {3}, pmid = {35747313}, issn = {1753-4313}, abstract = {There is emerging evidence that a proportion of patients who develop long (post)-COVID-19 have abnormalities in the regulation of their autonomic nervous system manifesting as postural tachycardia syndrome (PoTS). We report a series of 14 patients who developed symptoms and signs compatible with PoTS following clinically diagnosed COVID-19 infection. Their symptoms and clinical findings were consistent with those of patients with non-COVID-related PoTS. The authors recommend an active stand test for patients who present after COVID-19 infection with cardiovascular symptoms including chest pain, palpitations, lightheadedness and breathlessness that are worse with the upright posture. They further recommend training of clinicians and investment in health services to provide for the anticipated significant increase in patients presenting with PoTS and other forms of autonomic dysfunction due to the COVID-19 pandemic.}, } @article {pmid35747312, year = {2022}, author = {Opie, M and Nuttall, M}, title = {Pipedreams, the pandemic and PoTS: is the post-COVID-19 era a turning point for PoTS services?.}, journal = {The British journal of cardiology}, volume = {29}, number = {1}, pages = {7}, pmid = {35747312}, issn = {1753-4313}, } @article {pmid35747023, year = {2022}, author = {Touman, A and Kahyat, M and Bulkhi, A and Khairo, M and Alyamani, W and Aldobyany, AM and Ghaleb, N and Ashi, H and Alsobaie, M and Alqurashi, E}, title = {Post COVID-19 Chronic Parenchymal Lung Changes.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e25197}, pmid = {35747023}, issn = {2168-8184}, abstract = {INTRODUCTION: Persistent parenchymal lung changes are an important long-term sequela of COVID-19. There are limited data on this COVID-19 infection sequela characteristics and trajectories. This study aims to evaluate persistent COVID-19-related parenchymal lung changes 10 weeks after acute viral pneumonia and to identify associated risk factors.

METHODS: This is a retrospective case-control observational study involving 38 COVID-19 confirmed cases using nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) at King Abdullah Medical City (KAMC) Hospital, Makkah. Patients were recruited from the post-COVID-19 interstitial lung disease (ILD) clinic. Referral to this clinic was based on the pulmonology consultant's assessment of hospitalized patients suspected of developing COVID-19-related ILD changes during hospitalization.

RESULTS: Thirty-eight patients with parenchymal lung changes were evaluated at the ILD clinic. Nineteen patients who had persistent parenchymal changes 10 weeks after the acute illness (group 1) were compared with 19 control patients who had accelerated clinical and/or radiological improvement (group 2). Group 1 was found to have the more severe clinical and radiological disease, with a higher peak value of inflammatory biomarkers. Two risk factors were identified, neutrophil-lymphocyte ratio (NLR) > 3.13 at admission increases the odds ratio (OR) of chronic parenchymal changes by 6.42 and 5.92 in the univariate and multivariate analyses, respectively. Invasive mechanical ventilation had a more profound effect with ORs of 13.09 and 44.5 in the univariate and multivariate analyses, respectively.

CONCLUSION: Herein, we found that only receiving invasive mechanical ventilation and having NLR >3.13 at admission were strong risk factors for persistent parenchymal lung changes. Neither the clinical severity of the acute illness nor the radiological one is found to predict this outcome. None of the medications received during the acute illness were found to alter the risk for this post-COVID-19 infection sequelae.}, } @article {pmid35745708, year = {2022}, author = {Ruggiero, V and Aquino, RP and Del Gaudio, P and Campiglia, P and Russo, P}, title = {Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection.}, journal = {Pharmaceutics}, volume = {14}, number = {6}, pages = {}, pmid = {35745708}, issn = {1999-4923}, abstract = {Post-COVID syndrome or long COVID is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection, the pathogen responsible for coronavirus disease. The content herein presented reviews the reported long-term consequences and aftereffects of COVID-19 infection and the potential strategies to adopt for their management. Recent studies have shown that severe forms of COVID-19 can progress into acute respiratory distress syndrome (ARDS), a predisposing factor of pulmonary fibrosis that can irreversibly compromise respiratory function. Considering that the most serious complications are observed in the airways, the inhalation delivery of drugs directly to the lungs should be preferred, since it allows to lower the dose and systemic side effects. Although further studies are needed to optimize these techniques, recent studies have also shown the importance of in vitro models to recreate the SARS-CoV-2 infection and study its sequelae. The information reported suggests the necessity to develop new inhalation therapies in order to improve the quality of life of patients who suffer from this condition.}, } @article {pmid35743993, year = {2022}, author = {Tokumasu, K and Ueda, K and Honda, H and Sunada, N and Sakurada, Y and Matsuda, Y and Nakano, Y and Hasegawa, T and Otsuka, Y and Obika, M and Hagiya, H and Kataoka, H and Otsuka, F}, title = {Application of Kampo Medicines for Treatment of General Fatigue Due to Long COVID.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {6}, pages = {}, pmid = {35743993}, issn = {1648-9144}, mesh = {*COVID-19/complications ; Fatigue/drug therapy/etiology ; Humans ; Medicine, Kampo ; *Plants, Medicinal ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.}, } @article {pmid35743932, year = {2022}, author = {Bonsaksen, T and Leung, J and Price, D and Ruffolo, M and Lamph, G and Kabelenga, I and Thygesen, H and Geirdal, AØ}, title = {Self-Reported Long COVID in the General Population: Sociodemographic and Health Correlates in a Cross-National Sample.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {35743932}, issn = {2075-1729}, abstract = {We aimed to gain knowledge of possible sociodemographic predictors of long COVID and whether long COVID was associated with health outcomes almost two years after the pandemic outbreak. There were 1649 adults who participated in the study by completing a cross-sectional online survey disseminated openly in Norway, the UK, the USA, and Australia between November 2021 and January 2022. Participants were defined as having long COVID based on self-reports that they had been infected by COVID-19 and were experiencing long-lasting COVID symptoms. Logistic regression analyses were used to examine possible sociodemographic predictors, and multivariate analysis of variance was used to examine whether long COVID status was associated with health outcomes. None of the sociodemographic variables was significantly associated with reporting long COVID. Having long COVID was associated with higher levels of psychological distress, fatigue, and perceived stress. The effect of long COVID on health outcomes was greater among men than among women. In conclusion, long COVID appeared across sociodemographic groups. People with long COVID reported worsened health outcomes compared to those who had had COVID-19 but without long-term symptoms. Men experiencing long COVID appear to be particularly vulnerable to experiencing poorer health outcomes; health services may pay extra attention to potentially unnoticed needs for support among men experiencing long COVID.}, } @article {pmid35743774, year = {2022}, author = {Katsarou, MS and Iasonidou, E and Osarogue, A and Kalafatis, E and Stefanatou, M and Pappa, S and Gatzonis, S and Verentzioti, A and Gounopoulos, P and Demponeras, C and Konstantinidou, E and Drakoulis, N and Asimakos, A and Antonoglou, A and Mavronasou, A and Spetsioti, S and Kotanidou, A and Katsaounou, P}, title = {The Greek Collaborative Long COVID Study: Non-Hospitalized and Hospitalized Patients Share Similar Symptom Patterns.}, journal = {Journal of personalized medicine}, volume = {12}, number = {6}, pages = {}, pmid = {35743774}, issn = {2075-4426}, abstract = {Long COVID-19 syndrome refers to persisting symptoms (>12 weeks) after the initial coronavirus infection and is estimated to affect 3% to 12% of people diagnosed with the disease globally. Aim: We conducted a collaborative study with the Long COVID patient organization in Greece, in order to estimate the characteristics, symptoms, and challenges these patients confront. Methods: Data were collected from 208 patients using unstructured qualitative free-text entries in an anonymized online questionnaire. Results: The majority of respondents (68.8%) were not hospitalized and reported lingering symptoms (66.8%) for more than six months. Eighteen different symptoms (fatigue, palpitations, shortness of breath, parosmia, etc.) were mentioned in both hospitalized and community patients. Awareness of Long COVID sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still not included inthe management plan of Long COVID patients. Conclusions: Patients infected with coronavirus with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Long COVID syndrome appears to be a multi-systemic entity and a multidisciplinary medical approach should be adopted in order to correctly diagnose and successfully manage these patients.}, } @article {pmid35743516, year = {2022}, author = {Jennings, G and Monaghan, A and Xue, F and Duggan, E and Romero-Ortuño, R}, title = {Comprehensive Clinical Characterisation of Brain Fog in Adults Reporting Long COVID Symptoms.}, journal = {Journal of clinical medicine}, volume = {11}, number = {12}, pages = {}, pmid = {35743516}, issn = {2077-0383}, support = {20/COV/8493/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {(1) Introduction: A subset of individuals experiencing long COVID symptoms are affected by 'brain fog', a lay term that often refers to general cognitive dysfunction but one that is still poorly characterised. In this study, a comprehensive clinical characterisation of self-reported brain fog was conducted vis-à-vis other long COVID symptoms and parameters of mental, cognitive, and physical health. (2) Methodology: Adult participants reporting long COVID symptoms were recruited from hospital clinics and as self-referrals. Participants completed a battery of questionnaires and clinical assessments, including COVID-19 history, symptomatology, self-reported scales (Chalder Fatigue Scale [CFQ], Center for Epidemiological Studies Depression Scale, and Impact of Events Scale-Revised), computer-based cognitive assessments (simple response time and choice reaction time tasks), physical performance tests (gait velocity and muscle strength assessments), and an orthostatic active stand test. A systematic comparison between participants with and without self-reported brain fog was conducted, and a backwards binary logistic regression model was computed to identify the strongest independent associations with brain fog. This was complemented by an automatic cluster analysis to rank the importance of associations. Finally, a structural equation model was postulated with a causal model of key symptomatic indicators and functional consequences of brain fog as a latent variable. (3) Results: Of 108 participants assessed, brain fog was a self-reported symptom in 71 (65.7%) participants. Those with brain fog were at a longer point in time since COVID-19 onset and reported longer duration of low activity during the acute illness. When assessed, those with brain fog had higher frequencies of subjective memory impairment, word-finding difficulties, dizziness, myalgia, arthralgia, hyperhidrosis, cough, voice weakness, throat pain, visual and hearing problems, dysosmia, paraesthesia, chest pain, skin rashes, and hair loss; mean scores in fatigue, depression, and post-traumatic stress scales were higher; performance in both computer-based cognitive tasks was poorer; and measured gait speed and grip strength were lower. The logistic regression suggested that the best independent associations with brain fog were memory impairment, CFQ, and myalgia. The cluster analysis suggested that the most important associations with brain fog were CFQ, dizziness, myalgia, reduced gait speed, word-finding difficulties, reduced grip strength, and memory impairment. The SEM was consistent with key indicators of brain fog being CFQ, dizziness, myalgia, word-finding difficulties, and memory impairment; and reduced grip strength, gait speed, and cognitive response times its functional consequences. (4) Conclusions: The findings indicate that self-reported brain fog in long COVID is a recognisable symptom cluster primarily characterised by fatigue, dizziness, myalgia, word-finding difficulties, and memory impairment and has adverse psychological and psychomotor correlates. In long COVID, brain fog should be regarded as a wide-ranging symptom and addressed holistically with medical, psychological, and rehabilitative supports as guided by individual needs.}, } @article {pmid35742355, year = {2022}, author = {Clemente, I and Sinatti, G and Cirella, A and Santini, SJ and Balsano, C}, title = {Alteration of Inflammatory Parameters and Psychological Post-Traumatic Syndrome in Long-COVID Patients.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {12}, pages = {}, pmid = {35742355}, issn = {1660-4601}, mesh = {Anxiety/epidemiology/etiology ; C-Reactive Protein/analysis ; *COVID-19/complications ; Ferritins ; Humans ; L-Lactate Dehydrogenase ; SARS-CoV-2 ; *Sleep Wake Disorders ; Post-Acute COVID-19 Syndrome ; }, abstract = {The aim of our study is to evaluate the correlation between the psychological status of patients recovered from SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (long-COVID patients) and their inflammatory status. Three months after hospital discharge, ninety-three patients were recruited and categorized into two distinct populations: control and long-COVID (COrona VIrus Disease) group. Patients belonging to the control group presented with an entering diagnosis of cardiovascular, metabolic, or respiratory disease and a negative history of SARS-CoV-2 infection, whereas the long-COVID population presented with a severe SARS-CoV-2 infection treated in the sub-intensive Care Unit. Psychological evaluation was performed through the administration of the Symptom Checklist-90 (SCL90) and LDH (Lactate dehydrogenase), ferritin, CRPhs (C-high sensitivity Reactive Protein), NLR (Neutrophil-to-lymphocyte ratio), PLR (Platelet-to-lymphocyte ratio), and SII (systemic immune-inflammation index) were investigated. We highlighted that beyond the first three months after contagion, patients recovered from SARS-CoV-2 infection are characterized by the persistence of a systemic inflammatory state and are at high risk for developing somatization, depression, anxiety, and sleep disturbances. Interestingly, ferritin value was strongly correlated with sleep disorders (p < 0.05). Our study emphasizes how COVID-19 strategies for risk stratification, prognosis, and therapy management of patients should be implemented with a psychological follow-up.}, } @article {pmid35742231, year = {2022}, author = {Peters, C and Dulon, M and Westermann, C and Kozak, A and Nienhaus, A}, title = {Long-Term Effects of COVID-19 on Workers in Health and Social Services in Germany.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {12}, pages = {}, pmid = {35742231}, issn = {1660-4601}, mesh = {*COVID-19/epidemiology ; Female ; Germany/epidemiology ; Humans ; Quality of Life ; SARS-CoV-2 ; Social Work ; }, abstract = {Health workers are at increased risk for SARS-CoV-2 infections. What follows the acute infection is rarely reported in the occupational context. This study examines the employees' consequences of COVID-19 infection, the risk factors and the impact on quality of life over time. In this baseline survey, respondents were asked about their COVID-19 infection in 2020 and their current health situation. Out of 2053 participants, almost 73% experienced persistent symptoms for more than three months, with fatigue/exhaustion, concentration/memory problems and shortness of breath being most frequently reported. Risk factors were older age, female gender, previous illness, many and severe symptoms during the acute infection, and outpatient medical care. An impaired health-related quality of life was found in participants suffering from persistent symptoms. Overall, a high need for rehabilitation to improve health and work ability is evident. Further follow-up surveys will observe the changes and the impact of vaccination on the consequences of COVID-19 among health workers.}, } @article {pmid35742219, year = {2022}, author = {Villalpando, JMG and Forcelledo, HA and Castillo, JLB and Sastré, AJ and Rojop, IEJ and Hernández, VO and Canabal, FEM and Priego, CGG}, title = {COVID-19, Long COVID Syndrome, and Mental Health Sequelae in a Mexican Population.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {12}, pages = {}, pmid = {35742219}, issn = {1660-4601}, mesh = {Anxiety/epidemiology/psychology ; *COVID-19/complications/epidemiology ; Depression/epidemiology/psychology ; Humans ; Mental Health ; Pandemics ; SARS-CoV-2 ; Stress, Psychological/epidemiology/psychology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic is currently a worldwide threat and concern, not only because of COVID-19 itself but its sequelae. The aim of this study was to evaluate whether a relation between COVID-19, Long COVID, and the prevalence of mental health disorders exist. A total of 203 people from Tabasco were included in this study, answering a survey integrated by three dominions: General and epidemiological data, the DASS-21 test (to determine the presence of signs or symptoms suggestive of depression, anxiety, and/or stress) and an exploratory questionnaire about Long COVID syndrome. A descriptive and inferential statistical analysis was made via Microsoft Excel and Graphpad Prism software, evaluating differences through the Mann−Whitney U test and considering p < 0.05 as statistically significant. Of the 203 people surveyed, 96 (47.29%) had had COVID-19 and 107 (52.71%) had not; from the ones that had COVID-19, 29 (30.21%) presented mental health disorders and 88 (91.66%) presented at least one symptom or sign of Long COVID syndrome; meanwhile, 31 (32.29%) presented 10 or more symptoms or signs. From the comparison between the population with previous mental health disorders and COVID-19 and those without background disorders or COVID-19, the results were the following: 27.58% vs. 16.82% presented severe depression, 48.27% vs. 17.75% presented severe anxiety, and 27.58% vs. 20.56% presented severe stress. A high prevalence of mental health effects was observed in patients without COVID-19 and increased in the population with Long COVID syndrome and previous mental health disorders.}, } @article {pmid35741206, year = {2022}, author = {Manolescu, D and Timar, B and Bratosin, F and Rosca, O and Citu, C and Oancea, C}, title = {Predictors for COVID-19 Complete Remission with HRCT Pattern Evolution: A Monocentric, Prospective Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {6}, pages = {}, pmid = {35741206}, issn = {2075-4418}, abstract = {There are growing concerns that some COVID-19 survivors may acquire fibrosis and other irreversible lung abnormalities. The purpose of this prospective study was to assess the rate and predictors of complete resolution of COVID-19 pneumonia by pursuing a hypothetical relation between time and imaging pattern evolution using HRCT findings. A monocentric prospective cohort study with a consecutive-case enrolment design was implemented during a five-month period, having a total of 683 post-COVID patients eligible for inclusion and 635 evaluations with complete follow-up for chest HRCT. The target for post-COVID evaluations consisted of performing HRCT 90 days after a confirmed SARS-CoV-2 infection. The studied patients had an average age of 54 years, ranging between 18 and 85 years old, and an average duration from the first symptoms until HRCT was performed of 74 days. At the post-COVID follow-up, 25.8% had a complete imagistic remission. The most common appearance with HRCT was “ground glass” in 86.6% in patients with persistent COVID-19, followed by reticulations, present in 78.8%, and respectively pleural thickening in 41.2% of cases. The mean total HRCT scores were statistically significantly higher in patients older than 65 years (10.6 ± 6.0) compared to the 40−65 group (6.1 ± 6.1) and the 18−40 age group (2.7 ± 4.8) (p < 0.001). Chest HRCT is a “time window” in documenting temporal persistent radiologic features of lung injury 90 days after SARS-CoV-2 infection, determining the pathologic basis of so-called “long COVID”. The complete remission was associated with a significantly higher average follow-up period and a significantly lower average patient age. Persistent HRCT features of ground glass, reticulation, and pleural thickening are associated with a higher total CT score and older age.}, } @article {pmid35740354, year = {2022}, author = {Chilosi, M and Doglioni, C and Ravaglia, C and Martignoni, G and Salvagno, GL and Pizzolo, G and Bronte, V and Poletti, V}, title = {Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia.}, journal = {Biomedicines}, volume = {10}, number = {6}, pages = {}, pmid = {35740354}, issn = {2227-9059}, abstract = {Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome's evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes.}, } @article {pmid35739136, year = {2022}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Ayuzo Del Valle, NC and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S}, title = {Long-COVID in children and adolescents: a systematic review and meta-analyses.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9950}, pmid = {35739136}, issn = {2045-2322}, mesh = {Adolescent ; *Ageusia ; *COVID-19/complications/epidemiology ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Prevalence ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The objective of this systematic review and meta-analyses is to estimate the prevalence of long-COVID in children and adolescents and to present the full spectrum of symptoms present after acute COVID-19. We have used PubMed and Embase to identify observational studies published before February 10th, 2022 that included a minimum of 30 patients with ages ranging from 0 to 18 years that met the National Institute for Healthcare Excellence (NICE) definition of long-COVID, which consists of both ongoing (4 to 12 weeks) and post-COVID-19 (≥ 12 weeks) symptoms. Random-effects meta-analyses were performed using the MetaXL software to estimate the pooled prevalence with a 95% confidence interval (CI). Heterogeneity was assessed using I[2] statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed (registration PROSPERO CRD42021275408). The literature search yielded 8373 publications, of which 21 studies met the inclusion criteria, and a total of 80,071 children and adolescents were included. The prevalence of long-COVID was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%). Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls. Limitations of the studies analyzed include lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and a high level of heterogeneity.}, } @article {pmid35737279, year = {2022}, author = {Case, KR and Wang, CP and Hosek, MG and Lill, SF and Howell, AB and Taylor, BS and Bridges, J and MacCarthy, DJ and Winkler, P and Tsevat, J}, title = {Health-related quality of life and social determinants of health following COVID-19 infection in a predominantly Latino population.}, journal = {Journal of patient-reported outcomes}, volume = {6}, number = {1}, pages = {72}, pmid = {35737279}, issn = {2509-8020}, abstract = {BACKGROUND: As the COVID-19 pandemic evolves, more information is needed on its long-term impacts on health-related quality of life (HRQoL) and social determinants of health (SDoH). The aim of the study was to assess HRQoL and SDoH among a predominantly Latino population of COVID-19 survivors and to compare effects in Latinos versus non-Latinos.

METHODS: This cross-sectional study consisted of a survey (in English and Spanish) of COVID-19 survivors from December 2020 to July 2021. The study assessed sociodemographic data, clinical characteristics, and SDoH, consisting of 10 COVID-19-related concerns. The PROMIS-29 + 2 (PROPr) measure, which captures 8 HRQoL domains and a preference-based health utility, was used to assess HRQoL. Bivariate analyses included chi-square tests and t-tests. Generalized linear models were conducted for multivariable analyses.

RESULTS: Of 230 respondents (6.3% response rate), the mean [SD] age was 43.1 [14.3] years; 83.0% were Latino; the mean [SD] time since diagnosis was 8.1 [3.2] months; and 12.6% had a history of hospitalization with COVID-19. HRQoL scores were slightly worse than population norms on all domains, especially anxiety; the mean [SD] PROPr health utility was 0.36 [0.25]. Domain scores were similar by ethnicity except for cognitive function-abilities, where scores were lower in Latinos. Multivariable analyses revealed that: (1) financial concerns were associated with worse health utility, as well as worse scores on all 8 PROMIS domains; (2) interpersonal conflict was associated with worse health utility and worse scores on 6 of the 8 PROMIS domains (anxiety, depression, fatigue, sleep disturbance, social function, and pain interference); and (3) Latino ethnicity was only associated with 1 PROMIS domain (cognitive function-abilities) after controlling for covariates.

CONCLUSION: COVID-19 infection is associated with HRQoL decrements long after the acute infection, and financial concerns and interpersonal conflict are particularly associated with worse HRQoL.}, } @article {pmid35736595, year = {2022}, author = {McSpedon, C}, title = {Long COVID: What We Know Now.}, journal = {The American journal of nursing}, volume = {122}, number = {7}, pages = {20-22}, doi = {10.1097/01.NAJ.0000842232.15530.f1}, pmid = {35736595}, issn = {1538-7488}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {A growing population struggles with ongoing health problems.}, } @article {pmid35736479, year = {2022}, author = {Sonnweber, T and Grubwieser, P and Sahanic, S and Böhm, AK and Pizzini, A and Luger, A and Schwabl, C and Koppelstätter, S and Kurz, K and Puchner, B and Sperner-Unterweger, B and Hüfner, K and Wöll, E and Nairz, M and Widmann, G and Tancevski, I and Löffler-Ragg, J and Weiss, G}, title = {The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study.}, journal = {Metabolites}, volume = {12}, number = {6}, pages = {}, pmid = {35736479}, issn = {2218-1989}, support = {Project 17271//Austrian National bank Fund, J.LR/ ; n.a.//Verein zur Förderung von Forschung und Weiterbildung in Infektiologie und Immunologie, Innsbruck (G.We.)/ ; IIS 1199-0424//Boehringer Ingelheim RCV GmbH & Co KG (I.T.)/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study "Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)" encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome.}, } @article {pmid35736349, year = {2022}, author = {da Silveira Gorman, R and Syed, IU}, title = {Connecting the Dots in Emerging Mast Cell Research: Do Factors Affecting Mast Cell Activation Provide a Missing Link between Adverse COVID-19 Outcomes and the Social Determinants of Health?.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {35736349}, issn = {2076-3271}, mesh = {*COVID-19/complications ; Humans ; Mast Cells ; Pandemics ; Social Determinants of Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {Evidence continues to emerge that the social determinants of health play a role in adverse outcomes related to COVID-19, including increased morbidity and mortality, increased risk of long COVID, and vaccine adverse effects. Therefore, a more nuanced understanding of the biochemical and cellular pathways of illnesses commonly associated with adverse social determinants of health is urgently needed. We contend that a commitment to understanding adverse outcomes in historically marginalized communities will increase community-level confidence in public health measures. Here, we synthesize emerging literature on mast cell disease, and the role of mast cells in chronic illness, alongside emerging research on mechanisms of COVID illness and vaccines. We propose that a focus on aberrant and/or hyperactive mast cell behavior associated with chronic underlying health conditions can elucidate adverse COVID-related outcomes and contribute to the pandemic recovery. Standards of care for mast cell activation syndrome (MCAS), as well as clinical reviews, experimental research, and case reports, suggest that effective and cost-efficient remedies are available, including antihistamines, vitamin C, and quercetin, among others. Primary care physicians, specialists, and public health workers should consider new and emerging evidence from the biomedical literature in tackling COVID-19. Specialists and researchers note that MCAS is likely grossly under-diagnosed; therefore, public health agencies and policy makers should urgently attend to community-based experiences of adverse COVID outcomes. It is essential that we extract and examine experiential evidence of marginalized communities from the broader political-ideological discourse.}, } @article {pmid35734086, year = {2022}, author = {Torices, S and Motta, C and da Rosa, B and Marcos, A and Alvarez-Rosa, L and Siqueira, M and Moreno-Rodriguez, T and Matos, A and Caetano, B and Martins, J and Gladulich, L and Loiola, E and Bagshaw, O and Stuart, J and Siqueira, M and Stipursky, J and Toborek, M and Adesse, D}, title = {SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35734086}, issn = {2693-5015}, support = {R01 MH128022/MH/NIMH NIH HHS/United States ; R01 DA044579/DA/NIDA NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; R01 DA039576/DA/NIDA NIH HHS/United States ; R01 DA050528/DA/NIDA NIH HHS/United States ; R01 DA040537/DA/NIDA NIH HHS/United States ; R21 MH122235/MH/NIMH NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; }, abstract = {Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non- productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.}, } @article {pmid35734081, year = {2022}, author = {Durstenfeld, MS and Sun, K and Tahir, PM and Peluso, MJ and Deeks, SG and Aras, MA and Grandis, DJ and Long, CS and Beatty, A and Hsue, PY}, title = {Cardiopulmonary exercise testing to evaluate post-acute sequelae of COVID-19 ("Long COVID"): a systematic review and meta-analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.06.15.22276458}, pmid = {35734081}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; }, abstract = {IMPORTANCE: Reduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.

OBJECTIVES: To estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.

DATA SOURCES: We searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022.

STUDY SELECTION: We included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO 2 . 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers.

DATA EXTRACTION AND SYNTHESIS: Data extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models.

MAIN OUTCOMES AND MEASURES: A priori primary outcomes were differences in peak VO 2 (in ml/kg/min) among those with and without SARS-CoV-2 infection and LC.

RESULTS: We identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO 2 was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO 2 was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described.

CONCLUSIONS AND RELEVANCE: These studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.}, } @article {pmid35734080, year = {2022}, author = {Torices, S and Motta, CS and da Rosa, BG and Marcos, AC and Alvarez-Rosa, L and Siqueira, M and Moreno-Rodriguez, T and Matos, A and Caetano, B and Martins, J and Gladulich, L and Loiola, E and Bagshaw, OR and Stuart, JA and Siqueira, MM and Stipursky, J and Toborek, M and Adesse, D}, title = {SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {35734080}, issn = {2692-8205}, support = {R01 MH128022/MH/NIMH NIH HHS/United States ; R01 DA044579/DA/NIDA NIH HHS/United States ; R01 HL126559/HL/NHLBI NIH HHS/United States ; R01 DA039576/DA/NIDA NIH HHS/United States ; R01 DA050528/DA/NIDA NIH HHS/United States ; R01 DA040537/DA/NIDA NIH HHS/United States ; R21 MH122235/MH/NIMH NIH HHS/United States ; R01 DA047157/DA/NIDA NIH HHS/United States ; R01 MH072567/MH/NIMH NIH HHS/United States ; }, abstract = {Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non-productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.}, } @article {pmid35733875, year = {2022}, author = {Zhou, X and Yang, D and Kong, X and Wei, C and LvQiu, S and Wang, L and Lin, Y and Yin, Z and Zhou, Z and Luo, H}, title = {Case Report: Pirfenidone in the Treatment of Post-COVID-19 Pulmonary Fibrosis.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {925703}, pmid = {35733875}, issn = {2296-858X}, abstract = {BACKGROUND: Pulmonary fibrosis is one of the sequelae of the COVID-19, which seriously affects the quality of life of survivors. Currently, there are no optimal evidence based guidelines targeting this population.

CASE PRESENTATION: We report a 66-year-old female patient without underlying comorbidities admitted to Changsha Public Health Center because of COVID-19. During hospitalization, she developed co-bacterial infection and acute respiratory distress syndrome, and received broad-spectrum antibacterial therapy, invasive mechanical ventilation and extracorporeal membrane oxygenation. After the acute phase, she developed post-COVID-19 pulmonary fibrosis subsequently treated with pirfenidone. Over 96 weeks after pirfenidone treatment, her modified Medical Research Council Dyspnea level improved to 2 from 4 at discharge. Her 6 minutes walk test distance, total lung capacity, and diffusion capacity for carbon monoxide all increased. Chest CT performed on 2 years after illness onset showed regressing fibrosis. The Hospital Anxiety and Depression Scale, Athens Insomnia Scale, and 36-Item Short Form Health Survey questionnaire all improved.

CONCLUSION: Post-COVID-19 pulmonary fibrosis is a challenging consequence of COVID-19, and our case suggests that pirfenidone may be an effective treatment option.}, } @article {pmid35732153, year = {2022}, author = {Schultheiß, C and Willscher, E and Paschold, L and Gottschick, C and Klee, B and Henkes, SS and Bosurgi, L and Dutzmann, J and Sedding, D and Frese, T and Girndt, M and Höll, JI and Gekle, M and Mikolajczyk, R and Binder, M}, title = {The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.}, journal = {Cell reports. Medicine}, volume = {3}, number = {6}, pages = {100663}, pmid = {35732153}, issn = {2666-3791}, mesh = {*COVID-19/complications/immunology/pathology ; Cohort Studies ; *Cytokines/immunology ; Disease Progression ; Humans ; Immunologic Tests ; Interleukin-1beta/immunology ; Interleukin-6/immunology ; Tumor Necrosis Factor-alpha/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.}, } @article {pmid35731968, year = {2022}, author = {Mekhael, M and Lim, CH and El Hajjar, AH and Noujaim, C and Pottle, C and Makan, N and Dagher, L and Zhang, Y and Chouman, N and Li, DL and Ayoub, T and Marrouche, N}, title = {Studying the Effect of Long COVID-19 Infection on Sleep Quality Using Wearable Health Devices: Observational Study.}, journal = {Journal of medical Internet research}, volume = {24}, number = {7}, pages = {e38000}, pmid = {35731968}, issn = {1438-8871}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Polysomnography ; Sleep/physiology ; Sleep Quality ; *Wearable Electronic Devices ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Patients with COVID-19 have increased sleep disturbances and decreased sleep quality during and after the infection. The current published literature focuses mainly on qualitative analyses based on surveys and subjective measurements rather than quantitative data.

OBJECTIVE: In this paper, we assessed the long-term effects of COVID-19 through sleep patterns from continuous signals collected via wearable wristbands.

METHODS: Patients with a history of COVID-19 were compared to a control arm of individuals who never had COVID-19. Baseline demographics were collected for each subject. Linear correlations among the mean duration of each sleep phase and the mean daily biometrics were performed. The average duration for each subject's total sleep time and sleep phases per night was calculated and compared between the 2 groups.

RESULTS: This study includes 122 patients with COVID-19 and 588 controls (N=710). Total sleep time was positively correlated with respiratory rate (RR) and oxygen saturation (SpO2). Increased awake sleep phase was correlated with increased heart rate, decreased RR, heart rate variability (HRV), and SpO2. Increased light sleep time was correlated with increased RR and SpO2 in the group with COVID-19. Deep sleep duration was correlated with decreased heart rate as well as increased RR and SpO2. When comparing different sleep phases, patients with long COVID-19 had decreased light sleep (244, SD 67 vs 258, SD 67; P=.003) and decreased deep sleep time (123, SD 66 vs 128, SD 58; P=.02).

CONCLUSIONS: Regardless of the demographic background and symptom levels, patients with a history of COVID-19 infection demonstrated altered sleep architecture when compared to matched controls. The sleep of patients with COVID-19 was characterized by decreased total sleep and deep sleep.}, } @article {pmid35729924, year = {2022}, author = {Rivas-Vazquez, RA and Rey, G and Quintana, A and Rivas-Vazquez, AA}, title = {Correction to: Assessment and Management of Long COVID.}, journal = {Journal of health service psychology}, volume = {48}, number = {3}, pages = {141}, pmid = {35729924}, issn = {2662-2653}, abstract = {[This corrects the article DOI: 10.1007/s42843-022-00055-8.].}, } @article {pmid35728442, year = {2022}, author = {Freire, MP and Oliveira, MS and Magri, MMC and Tavares, BM and Marinho, I and Nastri, ACSS and Filho, GB and , and Levin, AS}, title = {Frequency and factors associated with hospital readmission after COVID-19 hospitalization: the importance of post-COVID diarrhea.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {77}, number = {}, pages = {100061}, pmid = {35728442}, issn = {1980-5322}, mesh = {Adult ; *COVID-19 ; COVID-19 Testing ; Diarrhea ; Female ; Hospitalization ; Humans ; Patient Readmission ; Prospective Studies ; }, abstract = {PURPOSE: The aim of this study was to describe the incidence and risk factors for hospital readmission and infection during the months after COVID-19 hospital admission.

METHODS: This prospective study included adult patients who were hospitalized due to COVID-19 and had been discharged from April 2020 to August 2020. All patients had a medical evaluation with a structured questionnaire 6 to 11 months after hospital admission. The authors included only patients with confirmed COVID-19 by RT-PCR. Patients with pregnant/postpartum women, with a proven COVID-19 reinfection or incapable of answering the questionnaire were excluded.

RESULTS: A total of 822 patients completed the follow-up assessment, and 68% reported at least one recurrent symptom related to COVID-19. The most frequent symptom was myalgia (42%). Thirty-two percent of patients visited an emergency room after COVID-19 hospitalization, and 80 (10%) patients required re-hospitalization. Risk factors for hospital readmission were orotracheal intubation during COVID-19 hospitalization (p = 0.003, OR = 2.14), Charlson score (p = 0.002, OR = 1.21), congestive heart failure (p = 0.005, OR = 2.34), peripheral artery disease (p = 0.06, OR = 2.06) and persistent diarrhea after COVID-19 hospitalization discharge (p = 0.02, OR = 1.91). The main cause of hospital readmission was an infection, 43 (54%). Pneumonia was the most frequent infection (29%).

CONCLUSIONS: The presence of symptoms after six months of COVID-19 diagnosis was frequent, and hospital readmission was relatively high.}, } @article {pmid35727926, year = {2022}, author = {Lapteva, ES and Ariev, AL and Arieva, GT and Tsutsunawa, MR and Diachkova-Gerceva, DC}, title = {[The role of geriatric services in the diagnosis and monitoring of outcomes of postcoital syndrome (review).].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {35}, number = {2}, pages = {191-205}, pmid = {35727926}, issn = {1561-9125}, mesh = {Aged ; *COVID-19/complications/diagnosis/epidemiology ; *Health Services for the Aged ; Humans ; Pandemics ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {In addition to the rapid and rippling spread of the pandemic across the globe today, there is a growing problem called «long-COVID-19», a term that describes the long-term effects of a new coronavirus infection COVID-19. How the disease proceeds after «recovery», including the long-term physical and psychological health consequences, the future of COVID-19 survivors remains largely unclear. This is especially true for the contingent older age groups. This article summarizes the experience of foreign studies aimed at determining the duration and clarifying the nature of multi-organ complications after undergoing COVID-19, as well as ways of long-term rehabilitation of patients in older age groups with post-COVID syndrome.}, } @article {pmid35727895, year = {2022}, author = {Mattioli, AV and Coppi, F and Nasi, M and Gallina, S}, title = {Stress and cardiovascular risk burden after the pandemic: current status and future prospects.}, journal = {Expert review of cardiovascular therapy}, volume = {20}, number = {7}, pages = {507-513}, doi = {10.1080/14779072.2022.2092097}, pmid = {35727895}, issn = {1744-8344}, mesh = {*COVID-19/complications ; *Cardiovascular Diseases/epidemiology/etiology ; Depression/epidemiology ; Female ; Heart Disease Risk Factors ; Humans ; Pandemics ; Risk Factors ; SARS-CoV-2 ; Stress, Psychological/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The recent COVID-19 pandemic has induced an increase in anxiety, stress, and depression in the world population, prompting a reevaluation of these well-known risk factors on cardiovascular burden.

AREAS COVERED: This short report analyzes the impact of the pandemic on stress and depression, highlighting how the phenomenon has particularly affected women and highlights the strategies that can be undertaken after the pandemic to reduce stress and depression. We have analyzed the pandemic because it has completely changed the scenario of cardiovascular risk factors with an important increase in socio-economic stressors.

EXPERT OPINION: It is still difficult to assess the damage produced on cardiovascular risk just as it is almost impossible to predict how the overwhelming and important increase in Long-Covid Syndromes will impact the population. Strong action is needed to support critical situations and to implement social campaigns aimed at restoring healthy lifestyles. Physical activity can be an easy and inexpensive tool to help cope with stress and depression.}, } @article {pmid35727635, year = {2022}, author = {Giron, LB and Peluso, MJ and Ding, J and Kenny, G and Zilberstein, NF and Koshy, J and Hong, KY and Rasmussen, H and Miller, GE and Bishehsari, F and Balk, RA and Moy, JN and Hoh, R and Lu, S and Goldman, AR and Tang, HY and Yee, BC and Chenna, A and Winslow, JW and Petropoulos, CJ and Kelly, JD and Wasse, H and Martin, JN and Liu, Q and Keshavarzian, A and Landay, A and Deeks, SG and Henrich, TJ and Abdel-Mohsen, M}, title = {Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.}, journal = {JCI insight}, volume = {7}, number = {15}, pages = {}, pmid = {35727635}, issn = {2379-3708}, support = {R01 AA029859/AA/NIAAA NIH HHS/United States ; R01 AI158013/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; R01 DK123733/DK/NIDDK NIH HHS/United States ; S10 OD023586/OD/NIH HHS/United States ; R24 AA026801/AA/NIAAA NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; R50 CA221838/CA/NCI NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Humans ; Inflammation ; Lectins, C-Type/metabolism ; NF-kappa B/metabolism ; SARS-CoV-2 ; Syk Kinase ; *beta-Glucans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.}, } @article {pmid35726132, year = {2022}, author = {Sylvester, SV and Rusu, R and Chan, B and Bellows, M and O'Keefe, C and Nicholson, S}, title = {Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review.}, journal = {Current medical research and opinion}, volume = {38}, number = {8}, pages = {1391-1399}, doi = {10.1080/03007995.2022.2081454}, pmid = {35726132}, issn = {1473-4877}, mesh = {*COVID-19/complications/epidemiology ; Disease Progression ; Female ; Humans ; Male ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: We conducted literature reviews to uncover differential effects of sex on sequelae from coronavirus disease 2019 (COVID-19) and on long COVID syndrome.

METHODS: Two authors independently searched OvidSP in Embase, Medline, Biosis, and Derwent Drug File. Publications reporting original, sex-disaggregated data for sequelae of COVID-19 (published before August 2020) and long COVID syndrome (published before June 2021) were included in the reviews. The association between COVID-19 sequelae (i.e. lasting <4 weeks after symptom onset) and sex, and between long COVID syndrome (i.e. lasting >4 weeks after symptom onset) and sex, was determined by odds ratio (OR) and 95% confidence interval (CI) (statistical significance defined by 95% CI not including 1).

RESULTS: Of 4346 publications identified, 23 and 12 met eligibility criteria for COVID-19 sequelae and long COVID syndrome, respectively. COVID-19 sequelae in the categories of psychiatric/mood (OR = 1.80; 95% CI: 1.35-2.41), ENT (OR = 1.42; 95% CI: 1.39-1.46), musculoskeletal (OR = 1.15; 95% CI: 1.14-1.16), and respiratory (OR = 1.09; 95% CI: 1.08-1.11) were significantly more likely among females (vs. males), whereas renal sequelae (OR = 0.83; 95% CI: 0.75-0.93) were significantly more likely among males. The likelihood of having long COVID syndrome was significantly greater among females (OR = 1.22; 95% CI: 1.13-1.32), with the odds of ENT (OR = 2.28; 95% CI: 1.94-2.67), GI (OR = 1.60; 95% CI: 1.04-2.44), psychiatric/mood (OR = 1.58; 95% CI: 1.37-1.82), neurological (OR = 1.30; 95% CI: 1.03-1.63), dermatological (OR = 1.29; 95% CI: 1.05-1.58), and other (OR = 1.36; 95% CI: 1.25-1.49) disorders significantly higher among females and the odds of endocrine (OR = 0.75; 95% CI: 0.69-0.81) and renal disorders (OR = 0.74; 95% CI: 0.64-0.86) significantly higher among males.

CONCLUSIONS: Sex-disaggregated differences for COVID-19 sequelae and long COVID syndrome were observed. Few COVID-19 studies report sex-disaggregated data, underscoring the need for further sex-based research/reporting of COVID-19 disease.}, } @article {pmid35725828, year = {2022}, author = {Ledford, H}, title = {How common is long COVID? Why studies give different answers.}, journal = {Nature}, volume = {606}, number = {7916}, pages = {852-853}, pmid = {35725828}, issn = {1476-4687}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Reproducibility of Results ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35725782, year = {2022}, author = {Wynberg, E and Han, AX and Boyd, A and van Willigen, HDG and Verveen, A and Lebbink, R and van der Straten, K and Kootstra, N and van Gils, MJ and Russell, C and Leenstra, T and de Jong, MD and de Bree, GJ and Prins, M and , }, title = {The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study.}, journal = {Vaccine}, volume = {40}, number = {32}, pages = {4424-4431}, pmid = {35725782}, issn = {1873-2518}, mesh = {Adult ; Bayes Theorem ; *COVID-19/prevention & control ; *COVID-19 Vaccines ; Humans ; Immunoglobulin G ; Prospective Studies ; SARS-CoV-2 ; Vaccination ; }, abstract = {BACKGROUND: Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC.

METHODS: RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression.

FINDINGS: Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46-5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183-324) and 181 (147-230) among participants with PASC, and 170 (125-252) and 144 (113-196) among those without PASC, respectively.

INTERPRETATION: Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.}, } @article {pmid35724998, year = {2022}, author = {Duong, D}, title = {The evolving picture of long COVID.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {194}, number = {24}, pages = {E850-E851}, doi = {10.1503/cmaj.1096004}, pmid = {35724998}, issn = {1488-2329}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35724689, year = {2022}, author = {Steenblock, C and Hassanein, M and Khan, EG and Yaman, M and Kamel, M and Barbir, M and Lorke, DE and Rock, JA and Everett, D and Bejtullah, S and Heimerer, A and Tahirukaj, E and Beqiri, P and Bornstein, SR}, title = {Diabetes and COVID-19: Short- and Long-Term Consequences.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {503-509}, pmid = {35724689}, issn = {1439-4286}, support = {Deutsche Forschungsgemeinschaft//288034826,314061271/ ; }, mesh = {*COVID-19/complications ; Communicable Disease Control ; *Diabetes Mellitus/epidemiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.}, } @article {pmid35724687, year = {2022}, author = {Bornstein, SR and Cozma, D and Kamel, M and Hamad, M and Mohammad, MG and Khan, NA and Saber, MM and Semreen, MH and Steenblock, C}, title = {Long-COVID, Metabolic and Endocrine Disease.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {562-566}, pmid = {35724687}, issn = {1439-4286}, support = {Deutsche Forschungsgemeinschaft//288034826,314061271/ ; }, mesh = {*COVID-19/complications ; *Endocrine System Diseases/complications/epidemiology/therapy ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In the aftermath of the corona pandemic, long-COVID or post-acute COVID-19 syndrome still represents a great challenge, and this topic will continue to represent a significant health problem in the coming years. At present, the impact of long-COVID on our health system cannot be fully assessed but according to current studies, up to 40% of people who have been infected with SARS-CoV-2 suffer from clinically relevant symptoms of long-COVID syndrome several weeks to months after the acute phase. The main symptoms are chronic fatigue, dyspnea, and various cognitive symptoms. Initial studies have shown that people with overweight and diabetes mellitus have a higher risk of developing long-COVID associated symptoms. Furthermore, repeated treatment of acute COVID-19 and long-COVID with steroids can contribute to long-term metabolic and endocrine disorders. Therefore, a structured program with rehabilitation and physical activity as well as optimal dietary management is of utmost importance, especially for patients with metabolic diseases and/or long-COVID. Furthermore, the removal of autoantibodies and specific therapeutic apheresis procedures could lead to a significant improvement in the symptoms of long-COVID in individual patients.}, } @article {pmid35724449, year = {2022}, author = {Newell, KL and Waickman, AT}, title = {Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infectionImmunity and inflammaion in post-acute sequelae of SARS-CoV-2 infection.}, journal = {Current opinion in immunology}, volume = {77}, number = {}, pages = {102228}, pmid = {35724449}, issn = {1879-0372}, mesh = {*COVID-19/complications ; Humans ; Inflammation ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection is known to result in a range of symptoms with varying degrees of acute-phase severity. In a subset of individuals, an equally diverse collection of long-term sequelae has been reported after convalescence. As survivorship and therefore the number of individuals with 'long-COVID' continues to grow, an understanding of the prevalence, origins, and mechanisms of post-acute sequelae manifestation is critically needed. Here, we will explore proposed roles of the anti-SARS-CoV-2 immune response in the onset, severity, and persistence of SARS-CoV-2 post-acute sequelae. We discuss the potential roles of persistent virus and autoantigens in this syndrome, as well as the contributions of unresolved inflammation and tissue injury. Furthermore, we highlight recent evidence demonstrating the potential benefits of vaccination and immunity in the resolution of post-acute symptoms.}, } @article {pmid35721785, year = {2022}, author = {Almas, T and Malik, J and Alsubai, AK and Jawad Zaidi, SM and Iqbal, R and Khan, K and Ali, M and Ishaq, U and Alsufyani, M and Hadeed, S and Alsufyani, R and Ahmed, R and Thakur, T and Huang, H and Antony, M and Antony, I and Bhullar, A and Kotait, F and Al-Ani, L}, title = {Post-acute COVID-19 syndrome and its prolonged effects: An updated systematic review.}, journal = {Annals of medicine and surgery (2012)}, volume = {80}, number = {}, pages = {103995}, pmid = {35721785}, issn = {2049-0801}, abstract = {OBJECTIVE: This systematic review aimed at estimating the prevalence of post-acute COVID-19 symptoms in view of published literature that studied prolonged clinical manifestations after recovery from acute COVID-19 infection.

METHODS: Relevant databases were searched for extraction of articles. For data synthesis, based on the distribution of quantitative variables, they were expressed as mean ± standard deviation (SD) or median and interquartile range (IQR). Qualitative variables were presented as frequency (n) and percentages (%).

RESULTS: Twenty-one articles qualified for the final analysis. The most common persistent clinical manifestations were fatigue (54.11%), dyspnea (24.38%), alopecia (23.21%), hyperhidrosis (23.6%), insomnia (25.98%), anxiety (17.29%), and arthralgia (16.35%). In addition to these symptoms, new-onset hypertension, diabetes, neuropsychiatric disorders, and bladder incontinence were also reported.

CONCLUSION: Clinical features of post-acute COVID-19 infection can manifest even after 60 days of initial infection. Multidisciplinary care along with regular follow-up must be provided to such patients.}, } @article {pmid35720240, year = {2022}, author = {Bogariu, AM and Dumitrascu, DL}, title = {Digestive involvement in the Long-COVID syndrome.}, journal = {Medicine and pharmacy reports}, volume = {95}, number = {1}, pages = {5-10}, pmid = {35720240}, issn = {2668-0572}, abstract = {BACKGROUND AND AIM: The SARS-CoV-2 infection which caused a worldwide epidemic was considered first a lung disease. Later on, it was found that the disease caused by this virus, SARS-CoV-2, can affect most organs, including the digestive system. The long-term effects of this infection are now progressively detected and called Long-COVID. This review aims is to present the updated knowledge of the digestive sequelae after SARS-CoV-2 infection.

METHODS: A search was performed in the main medical literature databases. The following search terms were used: long-covid, gastrointestinal or gastric sequelae SARS-CoV-2 and COVID-19. Data on gastrointestinal symptoms after 12 weeks were collected and presented. Observational studies were included. Studies that focus only on acute COVID-19 infection (<4 weeks) were excluded.

RESULTS: The main symptoms that can occur in the long term are: diarrhea, nausea, vomiting, abdominal pain, along with increased liver enzymes. Patients with chronic diseases have a higher risk of developing long-term sequelae, but it is not documented that digestive sequelae are influenced by the presence of chronic diseases.

CONCLUSIONS: The SARS-CoV-2 virus can affect any part of the digestive system not only in the acute infection phase but also for longer time, leaving long-term sequelae.}, } @article {pmid35717982, year = {2022}, author = {Antonelli, M and Pujol, JC and Spector, TD and Ourselin, S and Steves, CJ}, title = {Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2.}, journal = {Lancet (London, England)}, volume = {399}, number = {10343}, pages = {2263-2264}, pmid = {35717982}, issn = {1474-547X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Antibodies, Viral ; *COVID-19/complications ; Humans ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35717880, year = {2022}, author = {Grisanti, SG and Garbarino, S and Barisione, E and Aloè, T and Grosso, M and Schenone, C and Pardini, M and Biassoni, E and Zaottini, F and Picasso, R and Morbelli, S and Campi, C and Pesce, G and Massa, F and Girtler, N and Battaglini, D and Cabona, C and Bassetti, M and Uccelli, A and Schenone, A and Piana, M and Benedetti, L}, title = {Neurological long-COVID in the outpatient clinic: Two subtypes, two courses.}, journal = {Journal of the neurological sciences}, volume = {439}, number = {}, pages = {120315}, pmid = {35717880}, issn = {1878-5883}, mesh = {*Ageusia ; Ambulatory Care Facilities ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Symptoms referable to central and peripheral nervous system involvement are often evident both during the acute phase of COVID-19 infection and during long-COVID. In this study, we evaluated a population of patients with prior COVID-19 infection who showed signs and symptoms consistent with neurological long-COVID.

METHODS: We prospectively collected demographic and acute phase course data from patients with prior COVID-19 infection who showed symptoms related to neurological involvement in the long-COVID phase. Firstly, we performed a multivariate logistic linear regression analysis to investigate the impact of demographic and clinical data, the severity of the acute COVID-19 infection and hospitalization course, on the post-COVID neurological symptoms at three months follow-up. Secondly, we performed an unsupervised clustering analysis to investigate whether there was evidence of different subtypes of neurological long COVID-19.

RESULTS: One hundred and nine patients referred to the neurological post-COVID outpatient clinic. Clustering analysis on the most common neurological symptoms returned two well-separated and well-balanced clusters: long-COVID type 1 contains the subjects with memory disturbances, psychological impairment, headache, anosmia and ageusia, while long-COVID type 2 contains all the subjects with reported symptoms related to PNS involvement. The analysis of potential risk-factors among the demographic, clinical presentation, COVID 19 severity and hospitalization course variables showed that the number of comorbidities at onset, the BMI, the number of COVID-19 symptoms, the number of non-neurological complications and a more severe course of the acute infection were all, on average, higher for the cluster of subjects with reported symptoms related to PNS involvement.

CONCLUSION: We analyzed the characteristics of neurological long-COVID and presented a method to identify well-defined patient groups with distinct symptoms and risk factors. The proposed method could potentially enable treatment deployment by identifying the optimal interventions and services for well-defined patient groups, so alleviating long-COVID and easing recovery.}, } @article {pmid35717309, year = {2022}, author = {Stengel, S and Hoffmann, M and Koetsenruijter, J and Peters-Klimm, F and Wensing, M and Merle, U and Szecsenyi, J}, title = {[Long COVID: Care and support needs from the perspective of "long-haul" patients and primary care practitioners - a mixed-methods study from Baden-Wuerttemberg].}, journal = {Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen}, volume = {172}, number = {}, pages = {61-70}, pmid = {35717309}, issn = {2212-0289}, mesh = {Ambulatory Care ; Attitude of Health Personnel ; *COVID-19/complications/therapy ; Germany ; Humans ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The approaches to cope with the challenges of providing medical care to patients with symptoms of long COVID are multidisciplinary and involve primary care worldwide. The aim of this study was to explore the experiences and ideas for continued development of medical care of long COVID from the patients' (PAT) and primary care practitioners' (PCP) perspective.

METHODS: Between the third and fourth COVID-19 wave in Germany (July to September 2021), a mixed methods study was conducted by inviting patients and PCPs in two neighboring districts (urban and rural) in Baden-Wuerttemberg to a paper-based questionnaire with both closed and open questions. On the part of the PCPs a written, anonymized, complete survey was conducted, on the part of symptomatic COVID long-haulers an anonymized online survey with announcement of the study by multiple recruiting processes. Qualitative content analysis was applied to free text entries. The quantitative results were analyzed mainly descriptively.

RESULTS: The responses of n = 72 PCPs (response rate 12%) and n = 126 PAT showed a heterogeneous assessment regarding the satisfaction with medical care for long COVID as well as the perception of the attitude towards patients and their disease in both groups. Uncertainty and dealing with it played a relevant role in both groups as well. The professional medical knowledge was assessed by 3,1 (self-assessment PCPs) and 3,2 (PAT) on average using a five-point Likert scale (1 = not applicable; 5 = applicable). The request for a structured overall concept with competent contact points and coordination of medical care for long COVID patients emerged out of the statements of both groups.

CONCLUSION: The results support an interdisciplinary, intersectoral and interprofessional stepped-care concept for long COVID in Germany with PCPs as the first contact persons, integration of specialized contact points and knowledge transfer. Therefore, it appears to be both reasonable and appropriate to establish regional networks with links between regional outpatient medical care structures and the university medical sector.}, } @article {pmid35715663, year = {2023}, author = {Emecen, AN and Keskin, S and Turunc, O and Suner, AF and Siyve, N and Basoglu Sensoy, E and Dinc, F and Kilinc, O and Avkan Oguz, V and Bayrak, S and Unal, B}, title = {The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study.}, journal = {Irish journal of medical science}, volume = {192}, number = {2}, pages = {741-750}, pmid = {35715663}, issn = {1863-4362}, mesh = {Humans ; Female ; *COVID-19/epidemiology ; SARS-CoV-2 ; Longitudinal Studies ; RNA, Viral ; Hospitalization ; Post-Acute COVID-19 Syndrome ; Fatigue ; Dyspnea/epidemiology/etiology ; }, abstract = {BACKGROUND: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare.

AIMS: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms.

METHODS: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms.

RESULTS: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57-1.93), bad economic status (OR 1.37, 1.14-1.65), current smoking (OR 1.15, 1.02-1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40-0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33-2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19-2.78), and hospitalization (intensive care unit, OR 2.18, 1.51-3.14) were associated with reporting of symptoms.

CONCLUSIONS: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation.}, } @article {pmid35714995, year = {2022}, author = {Wise, J}, title = {Covid-19: Long covid risk is lower with omicron than delta, researchers find.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {o1500}, doi = {10.1136/bmj.o1500}, pmid = {35714995}, issn = {1756-1833}, mesh = {*COVID-19/complications ; Humans ; Research Personnel ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35714658, year = {2022}, author = {Munblit, D and Nicholson, T and Akrami, A and Apfelbacher, C and Chen, J and De Groote, W and Diaz, JV and Gorst, SL and Harman, N and Kokorina, A and Olliaro, P and Parr, C and Preller, J and Schiess, N and Schmitt, J and Seylanova, N and Simpson, F and Tong, A and Needham, DM and Williamson, PR and , }, title = {A core outcome set for post-COVID-19 condition in adults for use in clinical practice and research: an international Delphi consensus study.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {7}, pages = {715-724}, pmid = {35714658}, issn = {2213-2619}, support = {001/WHO_/World Health Organization/International ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Delphi Technique ; Humans ; Outcome Assessment, Health Care ; Research Design ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Health consequences that persist beyond the acute infection phase of COVID-19, termed post-COVID-19 condition (also commonly known as long COVID), vary widely and represent a growing global health challenge. Research on post-COVID-19 condition is expanding but, at present, no agreement exists on the health outcomes that should be measured in people living with the condition. To address this gap, we conducted an international consensus study, which included a comprehensive literature review and classification of outcomes for post-COVID-19 condition that informed a two-round online modified Delphi process followed by an online consensus meeting to finalise the core outcome set (COS). 1535 participants from 71 countries were involved, with 1148 individuals participating in both Delphi rounds. Eleven outcomes achieved consensus for inclusion in the final COS: fatigue; pain; post-exertion symptoms; work or occupational and study changes; survival; and functioning, symptoms, and conditions for each of cardiovascular, respiratory, nervous system, cognitive, mental health, and physical outcomes. Recovery was included a priori because it was a relevant outcome that was part of a previously published COS on COVID-19. The next step in this COS development exercise will be to establish the instruments that are most appropriate to measure these core outcomes. This international consensus-based COS should provide a framework for standardised assessment of adults with post-COVID-19 condition, aimed at facilitating clinical care and research worldwide.}, } @article {pmid35714657, year = {2022}, author = {Munblit, D and Buonsenso, D and Sigfrid, L and Vijverberg, SJH and Brackel, CLH}, title = {Post-COVID-19 condition in children: a COS is urgently needed.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {7}, pages = {628-629}, pmid = {35714657}, issn = {2213-2619}, mesh = {*COVID-19 ; Child ; Humans ; }, } @article {pmid35711381, year = {2022}, author = {Doeblin, P and Steinbeis, F and Scannell, CM and Goetze, C and Al-Tabatabaee, S and Erley, J and Faragli, A and Pröpper, F and Witzenrath, M and Zoller, T and Stehning, C and Gerhardt, H and Sánchez-González, J and Alskaf, E and Kühne, T and Pieske, B and Tschöpe, C and Chiribiri, A and Kelle, S}, title = {Brief Research Report: Quantitative Analysis of Potential Coronary Microvascular Disease in Suspected Long-COVID Syndrome.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {877416}, pmid = {35711381}, issn = {2297-055X}, abstract = {BACKGROUND: Case series have reported persistent cardiopulmonary symptoms, often termed long-COVID or post-COVID syndrome, in more than half of patients recovering from Coronavirus Disease 19 (COVID-19). Recently, alterations in microvascular perfusion have been proposed as a possible pathomechanism in long-COVID syndrome. We examined whether microvascular perfusion, measured by quantitative stress perfusion cardiac magnetic resonance (CMR), is impaired in patients with persistent cardiac symptoms post-COVID-19.

METHODS: Our population consisted of 33 patients post-COVID-19 examined in Berlin and London, 11 (33%) of which complained of persistent chest pain and 13 (39%) of dyspnea. The scan protocol included standard cardiac imaging and dual-sequence quantitative stress perfusion. Standard parameters were compared to 17 healthy controls from our institution. Quantitative perfusion was compared to published values of healthy controls.

RESULTS: The stress myocardial blood flow (MBF) was significantly lower [31.8 ± 5.1 vs. 37.8 ± 6.0 (μl/g/beat), P < 0.001] and the T2 relaxation time was significantly higher (46.2 ± 3.6 vs. 42.7 ± 2.8 ms, P = 0.002) post-COVID-19 compared to healthy controls. Stress MBF and T1 and T2 relaxation times were not correlated to the COVID-19 severity (Spearman r = -0.302, -0.070, and -0.297, respectively) or the presence of symptoms. The stress MBF showed a U-shaped relation to time from PCR to CMR, no correlation to T1 relaxation time, and a negative correlation to T2 relaxation time (Pearson r = -0.446, P = 0.029).

CONCLUSION: While we found a significantly reduced microvascular perfusion post-COVID-19 compared to healthy controls, this reduction was not related to symptoms or COVID-19 severity.}, } @article {pmid35709281, year = {2022}, author = {Couzin-Frankel, J}, title = {Clues to long COVID.}, journal = {Science (New York, N.Y.)}, volume = {376}, number = {6599}, pages = {1261-1265}, doi = {10.1126/science.add4297}, pmid = {35709281}, issn = {1095-9203}, abstract = {Scientists strive to unravel what is driving disabling symptoms.}, } @article {pmid35709270, year = {2022}, author = {Wadman, M}, title = {Glacial pace for U.S. Long Covid grants.}, journal = {Science (New York, N.Y.)}, volume = {376}, number = {6599}, pages = {1262-1263}, doi = {10.1126/science.add4321}, pmid = {35709270}, issn = {1095-9203}, mesh = {*COVID-19/complications/economics ; *Financing, Organized ; Humans ; National Institutes of Health (U.S.) ; United States ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35705825, year = {2022}, author = {Callaway, E}, title = {How months-long COVID infections could seed dangerous new variants.}, journal = {Nature}, volume = {606}, number = {7914}, pages = {452-455}, pmid = {35705825}, issn = {1476-4687}, mesh = {*COVID-19/virology ; Humans ; *SARS-CoV-2/classification/genetics ; Time Factors ; }, } @article {pmid35705219, year = {2022}, author = {Adab, P and Haroon, S and O'Hara, ME and Jordan, RE}, title = {Comorbidities and covid-19.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {o1431}, doi = {10.1136/bmj.o1431}, pmid = {35705219}, issn = {1756-1833}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/epidemiology ; Comorbidity ; Humans ; SARS-CoV-2 ; }, } @article {pmid35703982, year = {2022}, author = {Imoto, W and Yamada, K and Kakeya, H}, title = {Long COVID with intracranial microangiopathy.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {115}, number = {8}, pages = {539}, doi = {10.1093/qjmed/hcac139}, pmid = {35703982}, issn = {1460-2393}, mesh = {*COVID-19/complications ; Capillaries ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35702847, year = {2022}, author = {Taparia, NB}, title = {116 not out: A Case of long COVID Syndrome.}, journal = {The Journal of the Association of Physicians of India}, volume = {70}, number = {6}, pages = {11-12}, doi = {10.5005/japi-11001-0015}, pmid = {35702847}, issn = {0004-5772}, mesh = {Adult ; *COVID-19/complications ; Humans ; Male ; Pandemics ; *Respiratory Distress Syndrome/etiology/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 pandemic has caused havoc worldwide with huge health and financial losses to patients and relatives. It has wide clinical spectrum with acute respiratory distress syndrome (ARDS) as its primary manifestation. This also includes secondary infections developing post-COVID. Overall 10-15% of patients develop severe COVID and 5% become critically ill. Usually it takes 2-4 weeks to resolve. But few patients take unusually longer period to recover due to severe and serious complications. Some of them require prolonged ventilatory support and home oxygen and recover gradually with very high morbidity rates. We report a case of a 35-year-old male patient who was COVID-19 positive and took a long period of 116 days in-hospital stay to recover from illness in spite of having all possible complications.}, } @article {pmid35701643, year = {2022}, author = {Hofer, U}, title = {Animal model of long COVID?.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {8}, pages = {446}, pmid = {35701643}, issn = {1740-1534}, mesh = {Animals ; *COVID-19/complications ; Disease Models, Animal ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {A study in hamsters shows prolonged inflammatory changes after COVID-19.}, } @article {pmid35700481, year = {2022}, author = {Avery, RK}, title = {Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge.}, journal = {Transplantation}, volume = {106}, number = {8}, pages = {1528-1537}, pmid = {35700481}, issn = {1534-6080}, mesh = {Antibodies, Viral ; *COVID-19/complications/therapy ; Humans ; Immunization, Passive ; *Organ Transplantation/adverse effects ; SARS-CoV-2 ; Transplant Recipients ; COVID-19 Serotherapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12-18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.}, } @article {pmid35699134, year = {2022}, author = {Gattoni, C and Conti, E and Casolo, A and Nuccio, S and Baglieri, C and Capelli, C and Girardi, M}, title = {COVID-19 disease in professional football players: symptoms and impact on pulmonary function and metabolic power during matches.}, journal = {Physiological reports}, volume = {10}, number = {11}, pages = {e15337}, pmid = {35699134}, issn = {2051-817X}, mesh = {Adult ; Humans ; Male ; Young Adult ; *Athletic Performance/physiology ; *COVID-19 ; Muscle Fatigue ; *Running ; *Soccer/physiology ; }, abstract = {This study aimed at: (1) Reporting COVID-19 symptoms and duration in professional football players; (2) comparing players' pulmonary function before and after COVID-19; (3) comparing players' metabolic power (Pmet) before and after COVID-19. Thirteen male players (Age: 23.9 ± 4.0 years, V̇O2peak : 49.7 ± 4.0 mL/kg/min) underwent a medical screening and performed a running incremental step test and a spirometry test after COVID-19. Spirometric data were compared with the ones collected at the beginning of the same season. Players' mean Pmet of the 10 matches played before COVID-19 was compared with mean Pmet of the 10 matches played after COVID-19. Players completed a questionnaire on COVID-19 symptoms and duration 6 months following the disease. COVID-19 positivity lasted on average 15 ± 5 days. "General fatigue" and "muscle fatigue" symptoms were reported by all players during COVID-19 and persisted for 77% (general fatigue) and 54% (muscle fatigue) of the players for 37 ± 28 and 38 ± 29 days after the disease, respectively. No significant changes in spirometric measurements were found after COVID-19, even though some impairments at the individual level were observed. Conversely, a linear mixed-effects model analysis showed a significant reduction of Pmet (-4.1 ± 3.5%) following COVID-19 (t = -2.686, p < 0.05). "General fatigue" and "muscle fatigue" symptoms may persist for several weeks following COVID-19 in professional football players and should be considered for a safer return to sport. Players' capacity to compete at high intensities might be compromised after COVID-19.}, } @article {pmid35698920, year = {2022}, author = {Martone, AM and Tosato, M and Ciciarello, F and Galluzzo, V and Zazzara, MB and Pais, C and Savera, G and Calvani, R and Marzetti, E and Robles, MC and Ramirez, M and Landi, F and , }, title = {Sarcopenia as potential biological substrate of long COVID-19 syndrome: prevalence, clinical features, and risk factors.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {13}, number = {4}, pages = {1974-1982}, pmid = {35698920}, issn = {2190-6009}, support = {//Abbott Nutrition/ ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *COVID-19/complications ; Dyspnea ; Fatigue ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; *Sarcopenia/epidemiology/etiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Severe clinical pictures and sequelae of COVID-19 disease are immune mediated and characterized by a 'cytokine storm'. Skeletal muscle has emerged as a potent regulator of immune system function. The aim of the present study is to define the prevalence of sarcopenia among COVID-19 survivors and the negative impact of sarcopenia on the post-acute COVID-19 syndrome and its related risk factors.

METHODS: A total of 541 subjects recovered from COVID-19 disease were enrolled in the Gemelli Against COVID-19 Post-Acute Care between April 2020 and February 2021. They underwent a multidisciplinary clinical evaluation and muscle strength and physical performance assessment.

RESULTS: Mean age was 53.1 years (SD 15.2, range from 18 to 86 years), and 274 (51%) were women. The prevalence of sarcopenia was 19.5%, and it was higher in patients with a longer hospital stay and lower in patients who were more physically active and had higher levels of serum albumin. Patients with sarcopenia had a higher number of persistent symptoms than non-sarcopenic patients (3.8 ± 2.9 vs. 3.2 ± 2.8, respectively; P = 0.06), in particular fatigue, dyspnoea, and joint pain.

CONCLUSIONS: Sarcopenia identified according to the EWGSOP2 criteria is high in patients recovered from COVID-19 acute illness, particularly in those who had experienced the worst clinical picture reporting the persistence of fatigue and dyspnoea. Our data suggest that sarcopenia, through the persistence of inflammation, could be the biological substrate of long COVID-19 syndrome. Physical activity, especially if associated with adequate nutrition, seems to be an important protective factor.}, } @article {pmid35698804, year = {2022}, author = {Jonigk, D and Werlein, C and Lee, PD and Kauczor, HU and Länger, F and Ackermann, M}, title = {Pulmonary and Systemic Pathology in COVID-19—Holistic Pathological Analyses.}, journal = {Deutsches Arzteblatt international}, volume = {119}, number = {25}, pages = {429-435}, pmid = {35698804}, issn = {1866-0452}, support = {MR/R025673/1/MRC_/Medical Research Council/United Kingdom ; MR/S007687/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; Pandemics ; SARS-CoV-2 ; *Thrombosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic is the third worldwide coronavirus-associated disease outbreak in the past 20 years. Lung involvement, with acute respiratory distress syndrome (ARDS) in severe cases, is the main clinical feature of this disease; the cardiovascular system, the central nervous system, and the gastrointestinal tract can also be affected. The pathophysiology of both pulmonary and extrapulmonary organ damage was almost completely unknown when the pandemic began.

METHODS: This review is based on pertinent publications retrieved by a selective search concerning the structural changes and pathophysiology of COVID-19, with a focus on imaging techniques.

RESULTS: Immunohistochemical, electron-microscopic and molecular pathological analyses of tissues obtained by autopsy have improved our understanding of COVID-19 pathophysiology, including molecular regulatory mechanisms. Intussusceptive angiogenesis (IA) has been found to be a prominent pattern of damage in the affected organs of COVID-19 patients. In IA, an existing vessel changes by invagination of the endothelium and formation of an intraluminal septum, ultimately giving rise to two new lumina. This alters hemodynamics within the vessel, leading to a loss of laminar flow and its replacement by turbulent, inhomogeneous flow. IA, which arises because of ischemia due to thrombosis, is itself a risk factor for the generation of further microthrombi; these have been detected in the lungs, heart, liver, kidneys, brain, and placenta of COVID-19 patients.

CONCLUSION: Studies of autopsy material from various tissues of COVID-19 patients have revealed ultrastructural evidence of altered microvascularity, IA, and multifocal thrombi. These changes may contribute to the pathophysiology of post-acute interstitial fibrotic organ changes as well as to the clinical picture of long COVID.}, } @article {pmid35697699, year = {2022}, author = {Charnley, M and Islam, S and Bindra, GK and Engwirda, J and Ratcliffe, J and Zhou, J and Mezzenga, R and Hulett, MD and Han, K and Berryman, JT and Reynolds, NP}, title = {Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3387}, pmid = {35697699}, issn = {2041-1723}, mesh = {*COVID-19/complications ; Humans ; Peptides ; Proteome ; RNA, Viral ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don't understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.}, } @article {pmid35697054, year = {2022}, author = {Yang, C and Zhao, H and Tebbutt, SJ}, title = {A glimpse into long COVID and symptoms.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {9}, pages = {e81}, pmid = {35697054}, issn = {2213-2619}, support = {177747//CIHR/Canada ; }, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35697052, year = {2022}, author = {Huang, L and Gu, X and Zhang, H and Cao, B}, title = {A glimpse into long COVID and symptoms - Authors' reply.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {9}, pages = {e82}, pmid = {35697052}, issn = {2213-2619}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35696289, year = {2022}, author = {O'Kelly, B and Vidal, L and Avramovic, G and Broughan, J and Cotter, AG and Cullen, W and McHugh, T and O'Gorman, T and Woo, J and Lambert, JS}, title = {Predictors and Outcomes for COVID-19 Re-Admissions in the Anticipate Cohort.}, journal = {Irish medical journal}, volume = {115}, number = {5}, pages = {599}, pmid = {35696289}, issn = {0332-3102}, mesh = {Adult ; *COVID-19 ; Female ; Humans ; Male ; Middle Aged ; Nausea ; Patient Readmission ; Retrospective Studies ; Risk Factors ; Vomiting ; }, abstract = {Aims To describe readmissions of hospitalised patients with COVID-19, define predictors of readmission and explore the long term outcomes using the SF-12 score compared to patients who were not readmitted and those not hospitalised. Methods A single centre retrospective in North Inner-City Dublin. Recruitment was done through a COVID follow up clinic. Predictors of readmission and SF-12 scores at two timepoints post follow up at median 3 months and 12 months. Results Seventy (45%) participants were admitted, with a median age of 49.5 years (IQR 41.3-56.9), 36(51%) of whom were female. Unscheduled readmissions at ≤30 days in COVID-19 patients were 9(12.9%) and length of stay was four days (IQR 2-5). Readmissions were due to ongoing symptoms(n=9(64.3%)) or new complications(n=5(35.7%)). Mechanical ventilation and having symptoms of nausea and vomiting on index admission were predictive of readmission. (p=0.002). SF-12 scores at one year of readmitted patients were not different to patients who were never admitted at median one year follow up, p=.089. Conclusions Most readmissions were of short duration. Early follow up of patients post MV or who had nausea and vomiting on index admission should be prioritised. Wellbeing of readmitted patients was not different to those never hospitalised, at one year.}, } @article {pmid35693424, year = {2022}, author = {Qanneta, R}, title = {Long COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome: Similarities and differences of two peas in a pod.}, journal = {Reumatologia clinica}, volume = {18}, number = {10}, pages = {626-628}, pmid = {35693424}, issn = {1885-1398}, } @article {pmid35693009, year = {2022}, author = {Tate, W and Walker, M and Sweetman, E and Helliwell, A and Peppercorn, K and Edgar, C and Blair, A and Chatterjee, A}, title = {Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {877772}, pmid = {35693009}, issn = {1664-2295}, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from a viral infection, but also from other external stressors, like exposure to agricultural chemicals, other types of infection, surgery, or other severe stress events. Research has shown these events produce a systemic molecular inflammatory response and chronic immune activation and dysregulation. What has been more difficult to establish is the hierarchy of the physiological responses that give rise to the myriad of symptoms that ME/CFS patients experience, and why they do not resolve and are generally life-long. The severity of the symptoms frequently fluctuates through relapse recovery periods, with brain-centered symptoms of neuroinflammation, loss of homeostatic control, "brain fog" affecting cognitive ability, lack of refreshing sleep, and poor response to even small stresses. How these brain effects develop with ME/CFS from the initiating external effector, whether virus or other cause, is poorly understood and that is what our paper aims to address. We propose the hypothesis that following the initial stressor event, the subsequent systemic pathology moves to the brain via neurovascular pathways or through a dysfunctional blood-brain barrier (BBB), resulting in chronic neuroinflammation and leading to a sustained illness with chronic relapse recovery cycles. Signaling through recognized pathways from the brain back to body physiology is likely part of the process by which the illness cycle in the peripheral system is sustained and why healing does not occur. By contrast, Long COVID (Post-COVID-19 condition) is a very recent ME/CFS-like illness arising from the single pandemic virus, SARS-CoV-2. We believe the ME/CFS-like ongoing effects of Long COVID are arising by very similar mechanisms involving neuroinflammation, but likely with some unique signaling, resulting from the pathology of the initial SARS-CoV-2 infection. The fact that there are very similar symptoms in both ongoing diseases, despite the diversity in the nature of the initial stressors, supports the concept of a similar dysfunctional CNS component common to both.}, } @article {pmid35692134, year = {2023}, author = {Eslami, M and Mollazadeh, R and Mirshafiee, S and Sehat, P and Alizadeh, F and Emkanjoo, Z and Far, VL and Shahmohamadi, E}, title = {Postural Orthostatic Tachycardia Syndrome and Orthostatic Hypotension Post COVID-19.}, journal = {Infectious disorders drug targets}, volume = {23}, number = {1}, pages = {e100622205846}, doi = {10.2174/1871526522666220610143504}, pmid = {35692134}, issn = {2212-3989}, mesh = {Humans ; Male ; Aged ; Adult ; Middle Aged ; Female ; *Postural Orthostatic Tachycardia Syndrome/epidemiology/diagnosis ; *Hypotension, Orthostatic/etiology/diagnosis ; Cross-Sectional Studies ; Tilt-Table Test ; *COVID-19/complications ; }, abstract = {BACKGROUND: Novel coronavirus causes coronavirus disease -19 (COVID-19). The hallmark is acute respiratory distress syndrome, but other systems' involvement is less illustrated. Our goal was to evaluate the manifestation of COVID-19 on one of the overlaps of the cardiovascular and nervous system, namely: Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH).

METHODS: This single-center cross-sectional observational study encompassed 60 consecutive patients that were hospitalized and recovered from severe or critical COVID-19. At the time of discharge, Blood Pressure (BP) and Heart Rate (HR) in the supine and upright position (1st, 3rd, 5th and 10th minutes) were measured. Symptomatic patients were reevaluated 2 months later.

RESULTS: The mean age of patients was 56.6 (± 16.2) years and 42 patients were male (70%). The most frequent cardiovascular risk factor was hypertension (35%). OH and POTS were detected in 29(48.3%) and 10(16.7%) patients, respectively, at the time of hospital discharge. The mean age of patients with OH was higher than POTS and POTS was frequent in the elderly. Two months later, among 10 patients with POTS, the sign and symptoms were resolved in 8(80%). Two (20%) patients who still had positive signs and symptoms of POTS were older than 65 years. Among 29 patients with OH, the signs and symptoms were resolved in 26 (89.7%).

CONCLUSION: In our study, 65% of patients had OH or POTs on the day of hospital discharge; complete recovery is gradual and needs several additional weeks. This is one of the aspects of the entity recently named "Long COVID".}, } @article {pmid35690576, year = {2022}, author = {Thygesen, JH and Tomlinson, C and Hollings, S and Mizani, MA and Handy, A and Akbari, A and Banerjee, A and Cooper, J and Lai, AG and Li, K and Mateen, BA and Sattar, N and Sofat, R and Torralbo, A and Wu, H and Wood, A and Sterne, JAC and Pagel, C and Whiteley, WN and Sudlow, C and Hemingway, H and Denaxas, S and , }, title = {COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records.}, journal = {The Lancet. Digital health}, volume = {4}, number = {7}, pages = {e542-e557}, pmid = {35690576}, issn = {2589-7500}, support = {MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/2/MRC_/Medical Research Council/United Kingdom ; SP/19/3/34678/BHF_/British Heart Foundation/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/1/MRC_/Medical Research Council/United Kingdom ; CH/17/1/32804/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_UU_00004/08/MRC_/Medical Research Council/United Kingdom ; MR/S004149/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_18029/MRC_/Medical Research Council/United Kingdom ; 204841/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MR/S004149/2/MRC_/Medical Research Council/United Kingdom ; MR/K006584/1/MRC_/Medical Research Council/United Kingdom ; FS/18/5/33319/BHF_/British Heart Foundation/United Kingdom ; FS/11/38/28864/BHF_/British Heart Foundation/United Kingdom ; AA/18/6/24223/BHF_/British Heart Foundation/United Kingdom ; MR/L018942/1/MRC_/Medical Research Council/United Kingdom ; MC_UU_00019/4/MRC_/Medical Research Council/United Kingdom ; FS/14/76/30933/BHF_/British Heart Foundation/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; MR/T021780/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/epidemiology ; COVID-19 Testing ; Cohort Studies ; Electronic Health Records ; England/epidemiology ; Humans ; SARS-CoV-2 ; State Medicine ; }, abstract = {BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework.

METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status.

FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1.

INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources.

FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.}, } @article {pmid35690233, year = {2022}, author = {Sadat Larijani, M and Ashrafian, F and Bagheri Amiri, F and Banifazl, M and Bavand, A and Karami, A and Asgari Shokooh, F and Ramezani, A}, title = {Characterization of long COVID-19 manifestations and its associated factors: A prospective cohort study from Iran.}, journal = {Microbial pathogenesis}, volume = {169}, number = {}, pages = {105618}, pmid = {35690233}, issn = {1096-1208}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Iran/epidemiology ; Prospective Studies ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value < 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p < 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population.}, } @article {pmid35688881, year = {2022}, author = {Flemming, A}, title = {Vaccines only partially protect against Long COVID.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {7}, pages = {410}, pmid = {35688881}, issn = {1474-1741}, mesh = {*COVID-19/complications/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; *Vaccines ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35688830, year = {2022}, author = {Rigoni, M and Torri, E and Nollo, G and Donne, LD and Rizzardo, S and Lenzi, L and Falzone, A and Cozzio, S}, title = {"Long COVID" results after hospitalization for SARS-CoV-2 infection.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9581}, pmid = {35688830}, issn = {2045-2322}, mesh = {*COVID-19/complications/therapy ; Dyspnea/etiology ; Hospitalization ; Humans ; Prospective Studies ; Referral and Consultation ; Respiration, Artificial/methods ; SARS-CoV-2 ; Telephone ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term sequelae of symptomatic infection caused by SARS-CoV-2 are largely undiscovered. We performed a prospective cohort study on consecutively hospitalized Sars-CoV-2 patients (March-May 2020) for evaluating COVID-19 outcomes at 6 and 12 months. After hospital discharge, patients were addressed to two follow-up pathways based on respiratory support needed during hospitalization. Outcomes were assessed by telephone consultation or ambulatory visit. Among 471 patients, 80.9% received no respiratory support during hospitalization; 19.1% received non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV). 58 patients died during hospitalization, therefore 413 were enrolled for follow-up. At 6 months, among 355 patients, the 30.3% had any symptoms, 18.0% dyspnea, 6.2% neurological symptoms. Fifty-two out of 105 had major damages in interstitial computed tomography images. NIV/IMV patients had higher probability to suffer of symptoms (aOR = 4.00, 95%CI:1.99-8.05), dyspnea (aOR = 2.80, 95%CI:1.28-6.16), neurological symptoms (aOR = 9.72, 95%CI:2.78-34.00). At 12 months, among 344, the 25.3% suffered on any symptoms, 12.2% dyspnea, 10.1% neurological symptoms. Severe interstitial lesions were present in 37 out of 47 investigated patients. NIV/IMV patients in respect to no respiratory support, had higher probability of experiencing symptoms (aOR = 3.66, 95%CI:1.73-7.74), neurological symptoms (aOR = 8.96, 95%CI:3.22-24.90). COVID-19 patients showed prolonged sequelae up to 12 months, highlighting the need of follow-up pathways for post-COVID-19 syndrome.}, } @article {pmid35687603, year = {2022}, author = {Holdsworth, DA and Chamley, R and Barker-Davies, R and O'Sullivan, O and Ladlow, P and Mitchell, JL and Dewson, D and Mills, D and May, SLJ and Cranley, M and Xie, C and Sellon, E and Mulae, J and Naylor, J and Raman, B and Talbot, NP and Rider, OJ and Bennett, AN and Nicol, ED}, title = {Comprehensive clinical assessment identifies specific neurocognitive deficits in working-age patients with long-COVID.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0267392}, pmid = {35687603}, issn = {1932-6203}, mesh = {Acute Disease ; Adult ; *COVID-19/complications ; Fatigue/etiology ; Female ; Humans ; Lung ; Male ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity.

METHODS: Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness.

RESULTS: 205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness.

CONCLUSION: Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.}, } @article {pmid35687535, year = {2022}, author = {Cooper, S and Tobar, A and Konen, O and Orenstein, N and Kropach Gilad, N and Landau, YE and Mozer-Glassberg, Y and Bar-Lev, MR and Shaoul, R and Shamir, R and Waisbourd-Zinman, O}, title = {Long COVID-19 Liver Manifestation in Children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {75}, number = {3}, pages = {244-251}, pmid = {35687535}, issn = {1536-4801}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Infant ; Liver/pathology ; *Liver Failure, Acute/pathology ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury.

METHODS: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome.

RESULTS: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative.

CONCLUSIONS: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.}, } @article {pmid35686389, year = {2022}, author = {Lee, J and Kwon, KH}, title = {The significant transformation of life into health and beauty in metaverse era.}, journal = {Journal of cosmetic dermatology}, volume = {21}, number = {12}, pages = {6575-6583}, doi = {10.1111/jocd.15151}, pmid = {35686389}, issn = {1473-2165}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 ; *Cosmetics ; Marketing ; }, abstract = {BACKGROUND: In 2019, coronavirus disease-19 (COVID-19) continues, and it is evolving and starting again. It is a situation to keep in mind that now is the era of With Corona (WC) and Long-COVID. "WC" will be a transformation of the quarantine system. The current situation is associated with health and beauty. Sustainability of healthy beauty is giving new meaning to well-being and well-dying.

OBJECTIVES: Therefore, in this study, we empirically analyzed the changes in the perception of health and beauty among cosmetic consumers in the metaverse, which are recently becoming an issue in the WC era.

METHODS: It was created by searching keywords such as "With Corona," "Health," "Life Beauty," "Customized inner beauty," "Customized cosmetics," "Metaverse," "DTC GT," etc. This study was conducted with reference to PubMed, Google Scholar, Riss, Scopus, and ResearchGate. Accordingly, a total of 472 papers were researched, and among them, 32 papers, which are the focus of the study, were finally included in this study.

RESULTS: As the era of WC changes, a new paradigm of converting the customer experience of the beauty market into a metaverse will be beginning. Accordingly, it is necessary to pay attention to changes in the cosmetic industry by reflecting the needs of consumers.

CONCLUSION: It is necessary to create a new mobile platform that encompasses three-dimensional health and beauty life using direct-to-customer genetic testing (DTC GT) with Web 3.0 in the metaverse that integrates life health and beauty in the WC era. Accordingly, it is expected that this article will be used as an invaluable marketing material in preparation for new changes in the metaverse cosmetics market in the future by clearly understanding the needs of consumers in the cosmetics industry, which are changing as they transformation to WC era.}, } @article {pmid35684944, year = {2023}, author = {Dogas, T and Brkovic, T and Novak, I and Radic, J}, title = {COVID-19 in kidney transplant recipients; a DALMATIAN single-center experience.}, journal = {Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy}, volume = {27}, number = {1}, pages = {107-116}, pmid = {35684944}, issn = {1744-9987}, mesh = {Male ; Humans ; Female ; *COVID-19/epidemiology ; *Kidney Transplantation ; Immunosuppressive Agents/adverse effects ; Renal Replacement Therapy ; *Acute Kidney Injury/epidemiology ; }, abstract = {INTRODUCTION: We aimed to explore COVID-19 severity, complications, and outcome predictors in the Dalmatian population of kidney transplant recipients (KTRs).

METHODS: KTRs confirmed with acute COVID-19 infection until May 2021 were included and followed up for 6 months.

RESULTS: Out of 50 KTRs average aged 63 years, 36 (72%) were men. Nine (18%) KTRs had no pulmonary infiltration, and twenty-nine (58%) did not require oxygen supplementation. Bilateral pulmonary infiltrates had 29 (58%) while high-flow nasal cannula or mechanical ventilation required 8 (16%) KTRs. The mortality rate was 16%. Acute kidney injury developed in 18 (36%), and acute renal replacement therapy required 2 (4%) KTRs. Nine (18%) KTRs were subsequently rehospitalized. Chronic COVID-19 syndrome reported 23 (58%) KTRs.

CONCLUSIONS: D-dimers were found to be the key prognostic factor of clinical complications, emphasizing the importance of underlying thrombotic microangiopathy. Optimal immunosuppressant adjusting in KTRs with acute COVID-19 infection remains to be clarified.}, } @article {pmid35683480, year = {2022}, author = {Zhang, J and Shu, T and Zhu, R and Yang, F and Zhang, B and Lai, X}, title = {The Long-Term Effect of COVID-19 Disease Severity on Risk of Diabetes Incidence and the Near 1-Year Follow-Up Outcomes among Postdischarge Patients in Wuhan.}, journal = {Journal of clinical medicine}, volume = {11}, number = {11}, pages = {}, pmid = {35683480}, issn = {2077-0383}, support = {2020M680102//China Postdoctoral Science Foundation/ ; }, abstract = {We assessed the nearly 1-year health consequences following discharge and related risk factors of COVID-19 infection and further explored the long-term effect of COVID-19 disease severity on the risk of diabetes incidence. This prospective study included 248 COVID-19 patients discharged from Wuhan Hospital of Traditional Chinese Medicine who were followed up between 1 March and 10 June 2021. Logistic regression models were used to evaluate risk factors. The top ten symptoms were shortness of breath (30.3%), sore or dry throat (25.7%), cough (23.2%), expectoration (23.2%), body pain (22.3%), chest tightness (20.8%), palpitations (17.8%), sleep difficulties (17.0%), fatigue (16.6%), and anxiety (15.3%). Hypertension was associated with fatigue (OR = 2.51, 95% CI: 1.08, 5.80), shortness of breath (OR = 2.34, 95% CI: 1.16, 4.69), palpitations (OR = 2.82, 95% CI: 1.26, 6.31), expectoration (OR = 2.08, 95% CI: 1.01, 4.30), and sore or dry throat (OR = 2.71, 95% CI: 1.30, 5.65). Diabetes was associated with palpitations (OR = 3.22, 95% CI: 1.18, 8.81). Critical illness was associated with an increased risk of diabetes incidence after discharge (OR = 2.90, 95% CI: 1.07, 7.88), which seemed more evident in males. Long COVID-19 symptoms were common at 1-year postdischarge; hypertension and diabetes could be projected as potential risk factors. We are among the first researchers to find that critical illness is associated with incident diabetes after discharge.}, } @article {pmid35683388, year = {2022}, author = {Ayuso García, B and Romay Lema, E and Rabuñal Rey, R}, title = {Health Perception among Female COVID-19 Patients. Comment on Fernández-de-las-Peñas et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J. Clin. Med. 2022, 11, 413.}, journal = {Journal of clinical medicine}, volume = {11}, number = {11}, pages = {}, pmid = {35683388}, issn = {2077-0383}, abstract = {We read with interest the original paper by Fernández-de-las-Peñas et al. [...].}, } @article {pmid35682203, year = {2022}, author = {Yang, HJ and Setou, N and Koh, E}, title = {Utilization of Mind-Body Intervention for Integrative Health Care of COVID-19 Patients and Survivors.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {11}, pages = {}, pmid = {35682203}, issn = {1660-4601}, mesh = {Anxiety/psychology/therapy ; *COVID-19/epidemiology/therapy ; Communicable Disease Control ; Delivery of Health Care ; Humans ; Pandemics ; Randomized Controlled Trials as Topic ; Survivors ; *Yoga ; }, abstract = {Recent findings suggest a correlation between COVID-19 and diabetes, although the underlying causes are still little understood. COVID-19 infection tends to induce severe symptoms in patients with underlying diabetes, increasing their mortality rate. Moreover, COVID-19 itself appears to be a diabetogenic factor. In addition, mental health conditions, such as depression due to lockdown and anxiety about infection, were found to affect glycemic control and immunity, highlighting the importance of mental health care during the pandemic. Mind-Body Intervention (MBI), which includes meditation, yoga, and qigong, has emerged as a tool for mental health management due to its effects on stress reduction and the promotion of mental and physical well-being. Here, we review the latest randomized controlled trials to determine the effects of MBI on glycemic control and the immune system and discuss the underlying mechanisms by which MBI facilitates the virtuous cycle of stress management, glycemic control, and immune modulation. Furthermore, we examine the actual utilization of MBI during the COVID-19 pandemic era through recent studies. With proper online education, non-pharmacological MBI may be more widely used as an important tool for self-health care that complements the usual treatment of COVID-19 patients and survivors.}, } @article {pmid35679657, year = {2022}, author = {Eldokla, AM and Ali, ST}, title = {Autonomic function testing in long-COVID syndrome patients with orthostatic intolerance.}, journal = {Autonomic neuroscience : basic & clinical}, volume = {241}, number = {}, pages = {102997}, doi = {10.1016/j.autneu.2022.102997}, pmid = {35679657}, issn = {1872-7484}, mesh = {Blood Pressure ; *COVID-19/complications ; Heart Rate ; Humans ; *Hypotension, Orthostatic/diagnosis/etiology ; *Orthostatic Intolerance/diagnosis ; *Postural Orthostatic Tachycardia Syndrome/complications/diagnosis ; Retrospective Studies ; Tilt-Table Test ; Post-Acute COVID-19 Syndrome ; }, abstract = {The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.}, } @article {pmid35677075, year = {2022}, author = {Lai, P and Nguyen, L and Okin, D and Drew, D and Battista, V and Jesudasen, S and Kuntz, T and Bhosle, A and Thompson, K and Reinicke, T and Lo, CH and Woo, J and Caraballo, A and Berra, L and Vieira, J and Huang, CY and Adhikari, UD and Kim, M and Sui, HY and Magicheva-Gupta, M and McIver, L and Goldberg, M and Kwon, D and Huttenhower, C and Chan, A}, title = {Metagenomic assessment of gut microbial communities and risk of severe COVID-19.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35677075}, issn = {2693-5015}, support = {K01 DK120742/DK/NIDDK NIH HHS/United States ; K23 DK125838/DK/NIDDK NIH HHS/United States ; T32 HL116275/HL/NHLBI NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; }, abstract = {The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. We profiled 127 hospitalized patients with COVID-19 (n=79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. 48 species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID", suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with predicting whether stool was obtained from patients with severe vs. moderate COVID-19. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to validate these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.}, } @article {pmid35677073, year = {2023}, author = {Durstenfeld, MS and Peluso, MJ and Kaveti, P and Hill, C and Li, D and Sander, E and Swaminathan, S and Arechiga, VM and Lu, S and Goldberg, SA and Hoh, R and Chenna, A and Yee, BC and Winslow, JW and Petropoulos, CJ and Kelly, JD and Glidden, DV and Henrich, TJ and Martin, JN and Lee, YJ and Aras, MA and Long, CS and Grandis, DJ and Deeks, SG and Hsue, PY}, title = {Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.05.17.22275235}, pmid = {35677073}, support = {K12 HL143961/HL/NHLBI NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity using advanced cardiac testing.

METHODS: We performed cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; substudy of NCT04362150). Adults who completed a research echocardiogram (at a median 6 months after SARS-CoV-2 infection) without evidence of heart failure or pulmonary hypertension were asked to complete additional cardiopulmonary testing approximately 1 year later. Although participants were recruited as a prospective cohort, to account for selection bias, the primary analyses were as a case-control study comparing those with and without persistent cardiopulmonary symptoms. We also correlated findings with previously measured biomarkers. We used logistic regression and linear regression models to adjust for potential confounders including age, sex, body mass index, time since SARS-CoV-2 infection, and hospitalization for acute SARS-CoV-2 infection, with sensitivity analyses adjusting for medical history.

RESULTS: Sixty participants (unselected for symptoms, median age 53, 42% female, 87% non- hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On maximal CPET, 18/37 (49%) with symptoms had reduced exercise capacity (peak VO 2 <85% predicted) compared to 3/19 (16%) without symptoms (p=0.02). The adjusted peak VO 2 was 5.2 ml/kg/min (95%CI 2.1-8.3; p=0.001) or 16.9% lower actual compared to predicted (95%CI 4.3- 29.6; p=0.02) among those with symptoms compared to those without symptoms. Chronotropic incompetence was present among 12/21 (57%) with reduced VO 2 including 11/37 (30%) with symptoms and 1/19 (5%) without (p=0.04). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO 2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias on ambulatory monitoring were not present.

CONCLUSIONS: We found evidence of objectively reduced exercise capacity among those with cardiopulmonary symptoms more than 1 year following COVID-19, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary phenotype Long COVID.

KEY POINTS: Long COVID symptoms were associated with reduced exercise capacity on cardiopulmonary exercise testing more than 1 year after SARS-CoV-2 infection. The most common abnormal finding was chronotropic incompetence. Reduced exercise capacity was associated with early elevations in inflammatory markers.}, } @article {pmid35677013, year = {2022}, author = {Yellumahanthi, DK and Barnett, B and Barnett, S and Yellumahanthi, S}, title = {COVID-19 Infection: Its Lingering Symptoms in Adults.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24736}, pmid = {35677013}, issn = {2168-8184}, abstract = {Background Recent studies showed that a significant percentage of people who recovered from coronavirus disease 2019 (COVID-19) had lingering symptoms. Among patients diagnosed with COVID-19 infection, studies showed persistent symptoms both in patients hospitalized and in outpatient settings. In the studies done in the outpatient setting involving mild to moderate COVID-19 patients, there were significant variations regarding the exact percentage of people with lingering symptoms. Also, in the outpatient setting, not many studies were done on COVID-19 patients that assessed risk factors for having lingering symptoms. Given that a large percentage of people infected with COVID-19 infection do not get hospitalized, it is imperative that this lacuna be filled. We believe knowing the details of long-term symptoms of COVID-19 infection both from prevalence and predictors point of view, could allow the physicians, healthcare system and community to better prepare for managing and following these patients. Materials and methods Our study period was within 12 months after the first documented case of COVID-19 occurred in the State of Alabama. Our study population included patients who were diagnosed with a documented case of COVID-19 in this time period and were under the care of a single primary care provider at an ambulatory clinic. Among 80 patients who had documented COVID-19, three left the practice, two declined to participate in the study and three were deceased (two due to COVID-19 and one for other reasons). Therefore, the study population constituted 72 patients. A questionnaire was mailed to all 72 patients to see how many of them had symptoms three months and beyond of having COVID-19 infection. A chart review was conducted for the study participants to assess for "Comorbid conditions", health conditions that were considered conclusively high risk for acute COVID-19 infection by US Center for Disease Control and Prevention (CDC). Results Fifty-three patients responded to the questionnaire; 27 patients (50.9%) reported lingering symptoms beyond three months of diagnosis with COVID-19 infection. The three most common symptoms reported were fatigue (56%), brain fog (48%), and shortness of breath (41%). The results also showed that women are more likely than men to have lingering symptoms. "Elderly" (≥65 years) patients were as likely as 18-64 years old patients to have lingering symptoms and the presence of one or more of the "Comorbid conditions" does not have any bearing on the occurrence of lingering symptoms. Conclusion Future studies should be done in a larger population to assess the findings that our study showed regarding "elderly" age and the presence of one or more "comorbid conditions" being independent variables of the occurrence of prolonged COVID-19 symptoms. We recommend studies be done assessing the prevalence and predictors for the long-term effects of the COVID-19 infection. This knowledge could help in preventing those long-term symptoms from occurring in the first place and also in preparing the patient, the physician and the community in managing the outcomes effectively.}, } @article {pmid35676112, year = {2022}, author = {Vannini, L and Laynez-Carnicero, A and Bobis-Alvarez, C and Figueroa-Mora, A and Poncela-Mireles, J and Hernandez, FG}, title = {Accuracy of quality of life questionnaire as a diagnostic tool for SARS-CoV-2 pulmonary sequelae.}, journal = {Medicina clinica}, volume = {159}, number = {7}, pages = {330-333}, pmid = {35676112}, issn = {1578-8989}, mesh = {Adult ; Aged ; *COVID-19/diagnosis ; COVID-19 Testing ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Prospective Studies ; Quality of Life ; *SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Follow-up after hospital discharge of SARS-CoV-2 survivors represents a huge burden on the healthcare system. We attempt to assess the utility of symptoms and health-related quality of life questionnaire (SF-12) to identify SARS CoV2 pulmonary sequelae.

METHODS: Prospective, non-interventional follow-up study. A cardiopulmonary exercise test, functional respiratory test (PFT), SF12 questionnaire were performed after hospitalization at six months after the first positive PCR smear.

RESULTS: 41 patients were included, female (39%), mean age 57.3±13.7 years. 70% persisted with symptoms. 46% presented a maximum oxygen consumption below 80% of predicted. SF-12 physical domain score was significantly reduced in patients with altered PFT (32.7 vs. 45.9; p<0.001) and obtained the best sensitivity and specificity to identify PFT alterations (AUC 0.862, Sensitivity 85.7%, Specificity 81.5%).

CONCLUSIONS: SF-12 questionnaire shows high sensitivity and specificity to detect SARS CoV2 survivors with pulmonary function alterations.}, } @article {pmid35672483, year = {2022}, author = {Majithia, M and Ribeiro, SP}, title = {COVID-19 and Down syndrome: the spark in the fuel.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {7}, pages = {404-405}, pmid = {35672483}, issn = {1474-1741}, mesh = {*COVID-19 ; *Down Syndrome/genetics ; Humans ; }, abstract = {In individuals with Down syndrome, immune dysregulation is partially caused by chromosome 21 trisomy. Here, we discuss how these immune differences may result in poorer COVID-19 outcomes, including diminished responses to vaccination and possibly elevated risk for long COVID.}, } @article {pmid35672052, year = {2022}, author = {Kitsou, V and Blomberg, B and Lunde, T and Saeed, S}, title = {Intermittent left bundle branch block with septal flash and postural orthostatic tachycardia syndrome in a young woman with long COVID-19.}, journal = {BMJ case reports}, volume = {15}, number = {6}, pages = {}, pmid = {35672052}, issn = {1757-790X}, mesh = {Bundle-Branch Block/diagnosis ; *COVID-19/complications ; Dyspnea/etiology ; Female ; Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {The emerging entity, long COVID -19 is characterised by long-lasting dyspnoea, fatigue, cognitive dysfunction and other symptoms. Cardiac involvement manifested as conduction abnormalities, left ventricle mechanical dyssynchrony, dyspnoea, palpitation and postural orthostatic tachycardia syndrome (POTS) are common in long COVID-19. The direct viral damage to the myocardium or immune-mediated inflammation are postulated mechanisms. A woman in her forties presented with a 2-month history of chest pain, functional dyspnoea, palpitation and an episode of syncope after having been home-isolated for mild COVID infection. During clinical workup, a clustering of ECG and echocardiographic abnormalities including left bundle branch block, septal flash, and presystolic wave on spectral Doppler echocardiography, and POTS were detected. The echocardiographic findings together with POTS and persistent dyspnoea indicated the presence of a long COVID-19 state. The prevalence and clinical significance of these finding, as well as the impact on long-term prognosis, should be investigated in future studies.}, } @article {pmid35671044, year = {2022}, author = {Donnelly, SC}, title = {Long-COVID syndrome and the lung.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {115}, number = {6}, pages = {347}, doi = {10.1093/qjmed/hcac133}, pmid = {35671044}, issn = {1460-2393}, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35670916, year = {2022}, author = {Fernández-de-Las-Peñas, C and Varol, U and Gómez-Mayordomo, V and Cuadrado, ML and Valera-Calero, JA}, title = {The relevance of headache as an onset symptom in COVID-19: a network analysis of data from the LONG-COVID-EXP-CM multicentre study.}, journal = {Acta neurologica Belgica}, volume = {122}, number = {4}, pages = {1093-1095}, pmid = {35670916}, issn = {2240-2993}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; }, mesh = {*COVID-19/complications ; *Headache/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35669940, year = {2022}, author = {Young, P}, title = {[Sleep disorders and fatigue syndrome in long COVID syndrome: case-based experiences from neurological/sleep medicine rehabilitation].}, journal = {Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine}, volume = {26}, number = {2}, pages = {73-79}, pmid = {35669940}, issn = {1432-9123}, abstract = {Sleep disturbances and clinically significant fatigue syndrome are regularly described for long COVID syndrome. The pathophysiological correlations remain unknown. The clinical presentation is variable and must be considered individually. Four case studies will be used to illustrate the symptoms that constitute long COVID syndrome and the treatment options available. Multimodal individualized rehabilitation seems to be suitable to return those affected to their premorbid performance and to achieve a considerable reduction in insomniac complaints.}, } @article {pmid35669390, year = {2022}, author = {C, L and Upadhyaya, A and Neogi, AG and Niranjan, V}, title = {Identification of novel regulatory pathways across normal human bronchial epithelial cell lines (NHBEs) and peripheral blood mononuclear cell lines (PBMCs) in COVID-19 patients using transcriptome analysis.}, journal = {Informatics in medicine unlocked}, volume = {31}, number = {}, pages = {100979}, pmid = {35669390}, issn = {2352-9148}, abstract = {The SARS-CoV-2 is one of the most infectious and deadly coronaviruses, which has gripped the world, causing the COVID-19 pandemic. Despite the numerous studies being conducted on this virus, many uncertainties are with the disease. This is exacerbated by the speedy mutations acquired by the viral strain, which enables the disease to present itself differently in different people, introducing new factors of uncertainty. This study aims at the identification of regulatory pathways across two cell lines, namely, the peripheral blood mononuclear cell line (PBMC) and the normal human bronchial epithelial (NHBE) cell line. Both the above-mentioned cell lines were considered because they support viral replication. Furthermore, the NHBE cell line captures vital changes in the lungs, which are the main organs affected by the COVID-19 patients, and the PBMC cell line is closely linked to the body's immune system. RNA-Seq analysis, differential gene expression and gene set enrichment analysis for pathway identification were followed. Pathway analysis throws light upon the various systems affected in the body due to the COVID-19. Gene regulatory networks associated with the significant pathways were also designed. These networks aid in identifying various gene targets, along with their interactions. Studying the functionality of the pathways and the gene interactions associated with them, aided by long COVID studies, will provide immense clarity about the current COVID-19 scenario. In the long term, this will help in the design of therapeutic approaches against the SARS-CoV-2 and can also contribute to drug repurposing studies. Ultimately, this study identifies and analyses the relationship of various undiscovered or lesser explored pathways in the human body to the SARS-CoV-2 and establish a clearer picture of the association to help streamline further studies and approaches.}, } @article {pmid35669355, year = {2022}, author = {Noordzij, M}, title = {[Not Available].}, journal = {Nursing}, volume = {28}, number = {6}, pages = {42-48}, pmid = {35669355}, issn = {2468-1431}, } @article {pmid35667743, year = {2022}, author = {Dangayach, NS and Newcombe, V and Sonnenville, R}, title = {Acute Neurologic Complications of COVID-19 and Postacute Sequelae of COVID-19.}, journal = {Critical care clinics}, volume = {38}, number = {3}, pages = {553-570}, pmid = {35667743}, issn = {1557-8232}, mesh = {*COVID-19/complications ; Disease Progression ; Fatigue/complications ; Headache/complications ; Humans ; *Nervous System Diseases/etiology/therapy ; *Stroke ; }, abstract = {Neurologic complications can be seen in mild to severe COVID-19 with a higher risk in patients with severe COVID-19. These can occur as a direct consequence of viral infection or consequences of treatments. The spectrum ranges from non-life-threatening, like headache, fatigue, malaise, anosmia, dysgeusia, to life-threatening complications, like stroke, encephalitis, coma, Guillain-Barre syndrome. A high index of suspicion can aid in early recognition and treatment. Outcomes depend on severity of underlying COVID-19, patient age, comorbidities, and severity of the complication. Postacute sequelae of COVID-19 range from fatigue, headache, dysosmia, brain fog, anxiety, depression to an overlap with postintensive care syndrome.}, } @article {pmid35667737, year = {2022}, author = {Schwab, K and Schwitzer, E and Qadir, N}, title = {Postacute Sequelae of COVID-19 Critical Illness.}, journal = {Critical care clinics}, volume = {38}, number = {3}, pages = {455-472}, pmid = {35667737}, issn = {1557-8232}, mesh = {*COVID-19/complications/therapy ; Critical Illness/therapy ; Disease Progression ; Humans ; SARS-CoV-2 ; }, abstract = {With an ever-increasing number of COVID-19 survivors, providers are tasked with addressing the longer lasting symptoms of COVID-19, or postacute sequelae of SARS-CoV-2 infection (PASC). For critically ill patients, existing knowledge about postintensive care syndrome (PICS) represents a useful structure for understanding PASC. Post-ICU clinics leverage a multidisciplinary team to evaluate and treat the physical, cognitive, and psychological sequelae central to both PICS and PASC in critically ill patients. While management through both pharmacologic and nonpharmacologic modalities can be used, further research into both the optimal treatment and prevention of PASC represents a key public health imperative.}, } @article {pmid35665012, year = {2022}, author = {Reese, JT and Blau, H and Bergquist, T and Loomba, JJ and Callahan, T and Laraway, B and Antonescu, C and Casiraghi, E and Coleman, B and Gargano, M and Wilkins, KJ and Cappelletti, L and Fontana, T and Ammar, N and Antony, B and Murali, TM and Karlebach, G and McMurry, JA and Williams, A and Moffitt, R and Banerjee, J and Solomonides, AE and Davis, H and Kostka, K and Valentini, G and Sahner, D and Chute, CG and Madlock-Brown, C and Haendel, MA and Robinson, PN and , }, title = {Generalizable Long COVID Subtypes: Findings from the NIH N3C and RECOVER Programs.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.05.24.22275398}, pmid = {35665012}, support = {UL1 TR001445/TR/NCATS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; UL1 TR001436/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002556/TR/NCATS NIH HHS/United States ; }, abstract = {Accurate stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning procedures. Using k-means clustering of this similarity matrix, we found six distinct clusters of PASC patients, each with distinct profiles of phenotypic abnormalities. There was a significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. Two of the clusters were associated with severe manifestations and displayed increased mortality. We assigned new patients from other healthcare centers to one of the six clusters on the basis of maximum semantic similarity to the original patients. We show that the identified clusters were generalizable across different hospital systems and that the increased mortality rate was consistently observed in two of the clusters. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.}, } @article {pmid35664995, year = {2022}, author = {Hanson, SW and Abbafati, C and Aerts, JG and Al-Aly, Z and Ashbaugh, C and Ballouz, T and Blyuss, O and Bobkova, P and Bonsel, G and Borzakova, S and Buonsenso, D and Butnaru, D and Carter, A and Chu, H and De Rose, C and Diab, MM and Ekbom, E and El Tantawi, M and Fomin, V and Frithiof, R and Gamirova, A and Glybochko, PV and Haagsma, JA and Javanmard, SH and Hamilton, EB and Harris, G and Heijenbrok-Kal, MH and Helbok, R and Hellemons, ME and Hillus, D and Huijts, SM and Hultström, M and Jassat, W and Kurth, F and Larsson, IM and Lipcsey, M and Liu, C and Loflin, CD and Malinovschi, A and Mao, W and Mazankova, L and McCulloch, D and Menges, D and Mohammadifard, N and Munblit, D and Nekliudov, NA and Ogbuoji, O and Osmanov, IM and Peñalvo, JL and Petersen, MS and Puhan, MA and Rahman, M and Rass, V and Reinig, N and Ribbers, GM and Ricchiuto, A and Rubertsson, S and Samitova, E and Sarrafzadegan, N and Shikhaleva, A and Simpson, KE and Sinatti, D and Soriano, JB and Spiridonova, E and Steinbeis, F and Svistunov, AA and Valentini, P and van de Water, BJ and van den Berg-Emons, R and Wallin, E and Witzenrath, M and Wu, Y and Xu, H and Zoller, T and Adolph, C and Albright, J and Amlag, JO and Aravkin, AY and Bang-Jensen, BL and Bisignano, C and Castellano, R and Castro, E and Chakrabarti, S and Collins, JK and Dai, X and Daoud, F and Dapper, C and Deen, A and Duncan, BB and Erickson, M and Ewald, SB and Ferrari, AJ and Flaxman, AD and Fullman, N and Gamkrelidze, A and Giles, JR and Guo, G and Hay, SI and He, J and Helak, M and Hulland, EN and Kereselidze, M and Krohn, KJ and Lazzar-Atwood, A and Lindstrom, A and Lozano, R and Magistro, B and Malta, DC and Månsson, J and Herrera, AMM and Mokdad, AH and Monasta, L and Nomura, S and Pasovic, M and Pigott, DM and Reiner, RC and Reinke, G and Ribeiro, ALP and Santomauro, DF and Sholokhov, A and Spurlock, EE and Walcott, R and Walker, A and Wiysonge, CS and Zheng, P and Bettger, JP and Murray, CJ and Vos, T}, title = {A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {35664995}, support = {K23 NR019019/NR/NINR NIH HHS/United States ; R03 AG064303/AG/NIA NIH HHS/United States ; R21 AG061142/AG/NIA NIH HHS/United States ; U54 MD012530/MD/NIMHD NIH HHS/United States ; }, abstract = {IMPORTANCE: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.

OBJECTIVE: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.

DESIGN: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.

RESULTS: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.

CONCLUSIONS AND RELEVANCE: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.

KEY POINTS: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.}, } @article {pmid35664993, year = {2022}, author = {Muri, J and Cecchinato, V and Cavalli, A and Shanbhag, AA and Matkovic, M and Biggiogero, M and Maida, PA and Moritz, J and Toscano, C and Ghovehoud, E and Furlan, R and Barbic, F and Voza, A and Nadai, G and Cervia, C and Zurbuchen, Y and Taeschler, P and Murray, LA and Danelon-Sargenti, G and Moro, S and Gong, T and Piffaretti, P and Bianchini, F and Crivelli, V and Podešvová, L and Pedotti, M and Jarrossay, D and Sgrignani, J and Thelen, S and Uhr, M and Bernasconi, E and Rauch, A and Manzo, A and Ciurea, A and Rocchi, MBL and Varani, L and Moser, B and Bottazzi, B and Thelen, M and Fallon, BA and Boyman, O and Mantovani, A and Garzoni, C and Franzetti-Pellanda, A and Uguccioni, M and Robbiani, DF}, title = {Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {35664993}, issn = {2692-8205}, support = {P01 AI138938/AI/NIAID NIH HHS/United States ; U01 AI151698/AI/NIAID NIH HHS/United States ; U19 AI111825/AI/NIAID NIH HHS/United States ; }, abstract = {UNLABELLED: Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection. Anti-chemokine antibodies are present also in HIV-1 infection and autoimmune disorders, but they target different chemokines than those in COVID-19. Monoclonal antibodies derived from COVID- 19 convalescents that bind to the chemokine N-loop impair cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising anti-chemokine antibodies associated with favorable COVID-19 may be beneficial by modulating the inflammatory response and thus bear therapeutic potential.

ONE-SENTENCE SUMMARY: Naturally arising anti-chemokine antibodies associate with favorable COVID-19 and predict lack of long COVID.}, } @article {pmid35663839, year = {2022}, author = {Goldstein, CA and Kagan, D and Rizvydeen, M and Warshaw, S and Troost, JP and Burgess, HJ}, title = {The possibility of circadian rhythm disruption in long COVID.}, journal = {Brain, behavior, & immunity - health}, volume = {23}, number = {}, pages = {100476}, pmid = {35663839}, issn = {2666-3546}, } @article {pmid35662932, year = {2022}, author = {Surma, S and Sahebkar, A and Urbański, J and Penson, PE and Banach, M}, title = {Curcumin - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {865497}, pmid = {35662932}, issn = {2296-861X}, abstract = {Despite continuous advances in pharmacotherapy, atherosclerotic cardiovascular disease remains the world's leading killer. Atherosclerosis relates not only to an increased level of cholesterol, but involves the development of atherosclerotic plaques, which are formed as a result of processes including inflammation and oxidative stress. Therefore, in addition to the classical risk factors for ASCVD (such as type 2 diabetes, overweight, obesity, hypertension and metabolic syndrome), residual risk factors such as inflammation and oxidative stress should also be reduced. The most important intervention in ASCVD is prevention, which includes promoting a healthy diet based on products of natural origin. Curcumin, which is often present in the diet, has been demonstrate to confer several benefits to health. It has been shown in numerous clinical trials that curcumin exhibited anti-diabetic, lipid-lowering, antihypertensive, antioxidant and anti-inflammatory effects, as well as promoting weight loss. All this means that curcumin has a comprehensive impact on the most important risk factors of ASCVD and may be a beneficial support in the treatment of these diseases. Recently, it has also been shown that curcumin may have a beneficial effect on the course of SARS-CoV-2 infection and might be helpful in the prevention of long-COVID complications. The aim of this review is to summarize the current knowledge regarding the safety and efficacy of curcumin in the prevention and treatment of cardiometabolic diseases.}, } @article {pmid35662207, year = {2022}, author = {Poloni, TE and Medici, V and Zito, A and Carlos, AF}, title = {The long-COVID-19 in older adults: facts and conjectures.}, journal = {Neural regeneration research}, volume = {17}, number = {12}, pages = {2679-2681}, pmid = {35662207}, issn = {1673-5374}, } @article {pmid35660031, year = {2022}, author = {Leppkes, M and Neurath, MF}, title = {Rear Window-What Can the Gut Tell Us About Long-COVID?.}, journal = {Gastroenterology}, volume = {163}, number = {2}, pages = {376-378}, pmid = {35660031}, issn = {1528-0012}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35659358, year = {2022}, author = {Trapani, G and Verlato, G and Bertino, E and Maiocco, G and Vesentini, R and Spadavecchia, A and Dessì, A and Fanos, V}, title = {Long COVID-19 in children: an Italian cohort study.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {83}, pmid = {35659358}, issn = {1824-7288}, mesh = {Adolescent ; *COVID-19/complications/epidemiology ; Child ; Cohort Studies ; Female ; Hospitalization ; Humans ; Male ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection.

METHODS: Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents.

RESULTS: Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11-16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms.

CONCLUSIONS: Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.}, } @article {pmid35658801, year = {2022}, author = {Anaya, JM and Herrán, M and Beltrán, S and Rojas, M}, title = {Is post-COVID syndrome an autoimmune disease?.}, journal = {Expert review of clinical immunology}, volume = {18}, number = {7}, pages = {653-666}, doi = {10.1080/1744666X.2022.2085561}, pmid = {35658801}, issn = {1744-8409}, mesh = {*Autoimmune Diseases/epidemiology ; *COVID-19/epidemiology ; Humans ; SARS-CoV-2 ; Time Factors ; }, abstract = {INTRODUCTION: Post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development.

AREAS COVERED: The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment.

EXPERT OPINION: An autoimmune phenomenon plays a major role in most causative theories explaining PCS. There is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination's effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.}, } @article {pmid35658540, year = {2022}, author = {Lacavalerie, MR and Pierre-Francois, S and Agossou, M and Inamo, J and Cabie, A and Barnay, JL and Neviere, R}, title = {Obese patients with long COVID-19 display abnormal hyperventilatory response and impaired gas exchange at peak exercise.}, journal = {Future cardiology}, volume = {18}, number = {7}, pages = {577-584}, pmid = {35658540}, issn = {1744-8298}, mesh = {*COVID-19/complications ; Exercise/physiology ; Exercise Test ; Exercise Tolerance/physiology ; Humans ; Obesity/complications ; Oxygen Consumption/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Aim: To analyze the impact of obesity on cardiopulmonary response to exercise in people with chronic post-COVID-19 syndrome. Patients & methods: Consecutive subjects with chronic post-COVID syndrome 6 months after nonsevere acute infection were included. All patients received a complete clinical evaluation, lung function tests and cardiopulmonary exercise testing. A total of 51 consecutive patients diagnosed with chronic post-COVID-19 were enrolled in this study. Results: More than half of patients with chronic post-COVID-19 had a significant alteration in aerobic exercise capacity (VO2peak) 6 months after hospital discharge. Obese long-COVID-19 patients also displayed a marked reduction of oxygen pulse (O2pulse). Conclusion: Obese patients were more prone to have pathological pulmonary limitation and pulmonary gas exchange impairment to exercise compared with nonobese COVID-19 patients.}, } @article {pmid35658110, year = {2022}, author = {Wang, Y and Zheng, K and Gao, W and Lv, J and Yu, C and Wang, L and Wang, Z and Wang, B and Liao, C and Li, L}, title = {Asymptomatic and pre-symptomatic infection in Coronavirus Disease 2019 pandemic.}, journal = {Medical review (2021)}, volume = {2}, number = {1}, pages = {66-88}, pmid = {35658110}, issn = {2749-9642}, abstract = {With the presence of Coronavirus Disease 2019 (COVID-19) asymptomatic infections detected, their proportion, transmission potential, and other aspects such as immunity and related emerging challenges have attracted people's attention. We have found that based on high-quality research, asymptomatic infections account for at least one-third of the total cases, whereas based on systematic review and meta-analysis, the proportion is about one-fifth. Evaluating the true transmission potential of asymptomatic cases is difficult but critical, since it may affect national policies in response to COVID-19. We have summarized the current evidence and found, compared with symptomatic cases, the transmission capacity of asymptomatic individuals is weaker, even though they have similar viral load and relatively short virus shedding duration. As the outbreak progresses, asymptomatic infections have also been found to develop long COVID-19. In addition, the role of asymptomatic infection in COVID-19 remains to be further revealed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge. Nevertheless, as asymptomatic infections transmit the SARS-CoV-2 virus silently, they still pose a substantial threat to public health. Therefore, it is essential to conduct screening to obtain more knowledge about the asymptomatic infections and to detect them as soon as possible; meanwhile, management of them is also a key point in the fight against COVID-19 community transmission. The different management of asymptomatic infections in various countries are compared and the experience in China is displayed in detail.}, } @article {pmid35655148, year = {2022}, author = {Raza, S and Schwartz, B and Rosella, LC}, title = {CoQUAD: a COVID-19 question answering dataset system, facilitating research, benchmarking, and practice.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {210}, pmid = {35655148}, issn = {1471-2105}, mesh = {Algorithms ; *Benchmarking ; *COVID-19 ; Humans ; Language ; Natural Language Processing ; }, abstract = {BACKGROUND: Due to the growing amount of COVID-19 research literature, medical experts, clinical scientists, and researchers frequently struggle to stay up to date on the most recent findings. There is a pressing need to assist researchers and practitioners in mining and responding to COVID-19-related questions on time.

METHODS: This paper introduces CoQUAD, a question-answering system that can extract answers related to COVID-19 questions in an efficient manner. There are two datasets provided in this work: a reference-standard dataset built using the CORD-19 and LitCOVID initiatives, and a gold-standard dataset prepared by the experts from a public health domain. The CoQUAD has a Retriever component trained on the BM25 algorithm that searches the reference-standard dataset for relevant documents based on a question related to COVID-19. CoQUAD also has a Reader component that consists of a Transformer-based model, namely MPNet, which is used to read the paragraphs and find the answers related to a question from the retrieved documents. In comparison to previous works, the proposed CoQUAD system can answer questions related to early, mid, and post-COVID-19 topics.

RESULTS: Extensive experiments on CoQUAD Retriever and Reader modules show that CoQUAD can provide effective and relevant answers to any COVID-19-related questions posed in natural language, with a higher level of accuracy. When compared to state-of-the-art baselines, CoQUAD outperforms the previous models, achieving an exact match ratio score of 77.50% and an F1 score of 77.10%.

CONCLUSION: CoQUAD is a question-answering system that mines COVID-19 literature using natural language processing techniques to help the research community find the most recent findings and answer any related questions.}, } @article {pmid35655143, year = {2022}, author = {Baarsma, ME and Claassen, SA and van der Horst, HE and Hovius, JW and Sanders, JM}, title = {Knowing the entire story - a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease).}, journal = {BMC primary care}, volume = {23}, number = {1}, pages = {139}, pmid = {35655143}, issn = {2731-4553}, mesh = {*COVID-19/complications ; Focus Groups ; Humans ; Patient Outcome Assessment ; *Post-Lyme Disease Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them.

METHODS: Informed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes.

RESULTS: Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition).

CONCLUSION: Central themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.}, } @article {pmid35649534, year = {2022}, author = {Wise, J}, title = {Covid-19: Two million people in the UK are estimated to be experiencing long covid, says ONS.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {o1391}, doi = {10.1136/bmj.o1391}, pmid = {35649534}, issn = {1756-1833}, mesh = {*COVID-19/complications/epidemiology ; Humans ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35647079, year = {2022}, author = {Wood, G and Kirkevang, TS and Agergaard, J and Leth, S and Hansen, ESS and Laustsen, C and Larsen, AH and Jensen, HK and Østergaard, LJ and Bøtker, HE and Poulsen, SH and Kim, WY}, title = {Cardiac Performance and Cardiopulmonary Fitness After Infection With SARS-CoV-2.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {871603}, pmid = {35647079}, issn = {2297-055X}, abstract = {AIMS: Persistent cardiac symptoms are an increasingly reported phenomenon following COVID-19. However, the underlying cause of cardiac symptoms is unknown. This study aimed to identify the underlying causes, if any, of these symptoms 1 year following acute COVID-19 infection.

METHODS AND RESULTS: 22 individuals with persistent cardiac symptoms were prospectively investigated using echocardiography, cardiovascular magnetic resonance (CMR), 6-min walking test, cardio-pulmonary exercise testing and electrocardiography. A median of 382 days (IQR 368, 442) passed between diagnosis of COVID-19 and investigation. As a cohort their echocardiography, CMR, 6-min walking test and exercise testing results were within the normal ranges. There were no differences in left ventricular ejection fraction (61.45 ± 6.59 %), global longitudinal strain (19.80 ± 3.12 %) or tricuspid annular plane systolic excursion (24.96 ± 5.55 mm) as measured by echocardiography compared to a healthy control group. VO2 max (2045.00 ± 658.40 ml/min), % expected VO2 max (114.80 ± 23.08 %) and 6-minute distance walked (608.90 ± 54.51 m) exceeded that expected for the patient cohort, whilst Troponin I (5.59 ± 6.59 ng/l) and Nt-proBNP (88.18 ± 54.27 ng/l) were normal.

CONCLUSION: Among a cohort of 22 patients with self-reported persistent cardiac symptoms, we identified no underlying cardiac disease or reduced cardiopulmonary fitness 1 year following COVID-19.}, } @article {pmid35647070, year = {2022}, author = {Charfeddine, S and Ibnhadjamor, H and Jdidi, J and Torjmen, S and Kraiem, S and Bahloul, A and Makni, A and Kallel, N and Moussa, N and Boudaya, M and Touil, I and Ghrab, A and Elghoul, J and Meddeb, Z and Thabet, Y and Ben Salem, K and Addad, F and Bouslama, K and Milouchi, S and Hammami, R and Abdessalem, S and Abid, L}, title = {Sulodexide Significantly Improves Endothelial Dysfunction and Alleviates Chest Pain and Palpitations in Patients With Long-COVID-19: Insights From TUN-EndCOV Study.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {866113}, pmid = {35647070}, issn = {2297-055X}, abstract = {OBJECTIVE: Non-respiratory long-coronavirus disease 2019 (COVID-19) symptoms are mainly related to a long-lasting endothelial dysfunction and microcirculation impairment. We hypothesized that Sulodexide, a purified glycosaminoglycan mixture with a beneficial endothelial effect in arterial and venous peripheral diseases, may be effective in a subset of patients with long COVID-19.

APPROACH AND RESULTS: We conducted a multicenter prospective quasi-experimental study. A total of 290 patients from the TUN-EndCOV study with long-COVID-19 symptoms and endothelial dysfunction were included. The endothelial function was clinically assessed using a post-occlusive reactive hyperemia protocol with finger thermal monitoring device. Endothelial quality index (EQI) was assessed at inclusion and at 21 days later. The study population was assigned to a sulodexide group (144 patients) or a no-medical treatment group (146 patients). Clinical characteristics were similar at inclusion in the two groups. Fatigue, shortness of breath, and chest pain were the most common symptoms, respectively, 54.5, 53.8, and 28.3%. At 21 days, the sulodexide group improved significantly better than the no-medical treatment group in chest pain (83.7 vs. 43.6%, p < 10[-3]), palpitations (85.2 vs. 52.9%, p = 0.009), and endothelial function [median delta-EQI 0.66 (0.6) vs. 0.18 (0.3); p < 10[-3]]. Endothelial function improvement was significantly correlated with chest pain and palpitations recovery (AUC, i.e., area under the curve = 0.66, CI [0.57- 0.75], p = 0.001 and AUC = 0.60, CI [0.51- 0.69], p = 0.03, respectively).

CONCLUSION: Sulodexide significantly improves long-lasting post-COVID-19 endothelial dysfunction and alleviates chest pain and palpitations.}, } @article {pmid35646959, year = {2022}, author = {Cerasola, D and Argano, C and Corrao, S}, title = {Lessons From COVID-19: Physical Exercise Can Improve and Optimize Health Status.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {834844}, pmid = {35646959}, issn = {2296-858X}, abstract = {The outbreak of Coronavirus Disease 2019 (COVID-19) has caused increasing challenges for healthcare systems globally. The disease spread rapidly from Wuhan to the rest of the world, involving more than 400 million individuals and including more than 5 million deaths. In dealing with the pandemic, China and other countries took protective measures such as promoting social distancing, canceling public gatherings, closing schools, quarantining, and imposing lockdowns. All these measures lead to physical inactivity. Being physically inactive has significant repercussions on the status of physical and mental wellbeing, and it is associated with anxiety, stress, increased chronic disease risk, and worsening of chronic conditions. In this sense, the relevance of maintaining a healthy lifestyle through physical exercise has been outlined by the World Health Organization (WHO). The aim of this mini review is to discuss the importance of physical activity in the context of the COVID-19 pandemic, highlighting the benefits of physical activity and exercise that could be potentially effective treatment strategies for comorbid chronic conditions, long covid syndrome (LCS), and symptoms such as depression and anxiety.}, } @article {pmid35646346, year = {2022}, author = {Lahmer, T and Erber, J and Schmid, RM and Schneider, J and Spinner, CD and Luppa, P and Sörgel, F and Kinzig, M and Rasch, S}, title = {SARS-CoV-2 viral load dynamics in immunocompromised critically ill patients on remdesivir treatment.}, journal = {Multidisciplinary respiratory medicine}, volume = {17}, number = {}, pages = {825}, pmid = {35646346}, issn = {1828-695X}, abstract = {The relationship between SARS-CoV-2 quantitative viral load and risk of disease progression, morbidity such as long- COVID or mortality in immunosuppressed, remains largely undefined in COVID-19 patients. Critically ill immunosuppressed patients potentially benefit from remdesivir treatment because of the prolonged course of their infection. Four critically ill immunocompromised patients and the impact of remdesivir on viral dynamics in lower respiratory samples were studied. Bronchoalveolar lavage (BAL) samples were assessed to measure SARS-CoV-2 quantitative viral load using real-time PCR. Corresponding plasma levels of remdesivir and its metabolite GS-441524 were determined. Mean virus load of 39.74 x 10[7] geq/ml (±33.25 x 10[7] geq/ml) on day 1 dropped significantly (p<0.008) to 3.54 x 10[6] geq/ml (±6.93 x 10[6] geq/ml) on day 3 and to 1.4 x 10[5] geq/ml (±2.35 x 10[5] geq/ml) on day 5 of remdesivir treatment. Mean virus load dropped below <1% between day 1 and 5 of remdesivir treatment. Parent prodrug remdesivir and also GS441524 metabolite levels of antiviral activity in our patients were far in excess of EC 50. Our data present that remdesivir treatment potentially reduces the SARS-CoV-2 viral load in immunosuppressed critically ill patients. However, the implication of viral load reduction on morbidity and mortality needs further investigation.}, } @article {pmid35645833, year = {2022}, author = {Vuorio, A and Raal, F and Ijäs, P and Kaste, M and Kovanen, PT}, title = {Long-Term Cardiovascular and Cerebrovascular Challenges Posed by COVID-19 in Patients With Familial Hypercholesterolemia.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {890141}, pmid = {35645833}, issn = {1663-9812}, } @article {pmid35643305, year = {2022}, author = {Ali, M and Bonna, AS and Sarkar, AS and Islam, MA and Rahman, NA}, title = {SARS-CoV-2 infection is associated with low back pain: findings from a community-based case-control study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {122}, number = {}, pages = {144-151}, pmid = {35643305}, issn = {1878-3511}, mesh = {Adolescent ; Adult ; *COVID-19/complications/epidemiology ; Case-Control Studies ; Humans ; *Low Back Pain/epidemiology/etiology ; Odds Ratio ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: Pain is a significant complaint of patients with postacute COVID-19 syndrome; however, little is known about the association between SARS-CoV-2 infection and pain. This study aimed to (1) examine the association between SARS-CoV-2 infection and low back pain (LBP) and (2) identify independent predictors of LBP among survivors of COVID-19.

METHODS: This case-control study involved 878 participants aged ≥18 years. Data were collected from February 24 to April 7, 2022, in Bangladesh. LBP was measured using the musculoskeletal subscale of subjective health complaints produced by Eriksen et al. Descriptive analysis was performed to compute LBP prevalence and compare the prevalence across groups. Multiple logistic analyses helped to identify the predictors of LBP for survivors of COVID-19.

RESULTS: Overall, 20% of participants reported LBP; however, the prevalence of LBP was significantly high among patients with postacute COVID-19 compared with their counterparts (24.4% vs 15.7%, P = 0.001). Regression analysis for all participants suggested that SARS-CoV-2 infection was independently associated with LBP (adjusted odds ratio 1.837, 95% confidence interval 1.253-2.692). However, moderate COVID-19 symptom (adjusted odds ratio 1.754, 95% confidence interval 0.984-3.126) was the only statistically significant predictor of LBP among postacute COVID-19 patients.

CONCLUSION: SARS-CoV-2 infection was associated with LBP, and moderate COVID-19 symptom was an independently associated factor of LBP. The health care facilities must be prepared to deal with the burden of LBP among patients with postacute COVID-19.}, } @article {pmid35641057, year = {2022}, author = {Ebell, MH and Forgacs, D and Shen, Y and Ross, TM and Hulme, C and Bentivegna, M and Hanley, HB and Jefferson, AM and Hainess, L}, title = {High Prevalence of Both Previous Infection with SARS-CoV-2 and Persistent Symptoms.}, journal = {Journal of the American Board of Family Medicine : JABFM}, volume = {35}, number = {3}, pages = {570-578}, doi = {10.3122/jabfm.2022.03.210348}, pmid = {35641057}, issn = {1558-7118}, mesh = {*COVID-19/epidemiology ; Cross-Sectional Studies ; Humans ; Male ; Prevalence ; *SARS-CoV-2 ; Universities ; }, abstract = {INTRODUCTION: Universities are unique settings with large populations, congregate housing, and frequent attendance of events in large groups. However, the current prevalence of previous COVID-19 infection in university students, including symptomatic and asymptomatic disease, is unknown. Our goal therefore was to determine the prevalence of previous infection, risk factors for infection, and the prevalence of persistent symptoms following infection among university students.

METHODS: This was a cross-sectional study set in a large public university between January 22 and March 22, 2021. We surveyed students about demographics, risk factors, and symptoms, and simultaneously tested their saliva for IgA antibodies to SARS-CoV-2. To estimate the prevalence of previous infection we adjusted our intentional sample of a diverse student population for year in school and age to resemble the composition of the entire student body and adjusted for the imperfect sensitivity and specificity of the antibody test. Univariate and multiple regression analysis was used to identify independent risk factors for infection, and the proportion of students with persistent symptoms following acute infection was determined.

RESULTS: A total of 488 students completed the survey, 432 had a valid antibody result, and 428 had both. The estimated prevalence of previous infection for 432 participants with valid antibody results was 41%. Of 145 students in our sample with a positive antibody test, 41.4% denied having a previous positive polymerase chain reaction (PCR) test for SARS-CoV-2 and presumably had an asymptomatic infection; in our adjusted analysis we estimate that approximately 2-thirds of students had asymptomatic infections. Independent risk factors for infection included male sex, having a roommate with a known symptomatic infection, and having two or fewer roommates. More frequent attendance of parties and bars was a univariate risk factor, but not in the multiple regression analysis. Of 122 students reporting a previous symptomatic infection, 14 (11.4%) reported persistent symptoms consistent with postacute COVID-19 a median of 132 days later.

CONCLUSIONS AND RELEVANCE: Previous COVID-19 infection, both symptomatic and asymptomatic, was common at a large university. Measures that could prevent resurgence of the infection when students return to campus include mandatory vaccination policies, mass surveillance testing, and testing of sewage for antigen to SARS-CoV-2.}, } @article {pmid35637934, year = {2022}, author = {Töpfner, N and , and Alberer, M and Ankermann, T and , and Bender, S and , and Berner, R and de Laffolie, J and , and Dingemann, J and , and Heinicke, D and , and Haas, JP and , and Hufnagel, M and Hummel, T and , and Huppertz, HI and , and Knuf, M and Kobbe, R and Lücke, T and , and Riedel, J and , and Rosenecker, J and , and Wölfle, J and , and Schneider, B and , and Schneider, D and , and Schriever, V and , and Schroeder, A and , and Stojanov, S and Tenenbaum, T and Trapp, S and , and Vilser, D and , and Brinkmann, F and Behrends, U}, title = {[Recommendation for standardized medical care for children and adolescents with long COVID].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {170}, number = {6}, pages = {539-547}, pmid = {35637934}, issn = {0026-9298}, abstract = {This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.}, } @article {pmid35637413, year = {2022}, author = {Kanczkowski, W and Beuschlein, F and Bornstein, SR}, title = {Is there a role for the adrenal glands in long COVID?.}, journal = {Nature reviews. Endocrinology}, volume = {18}, number = {8}, pages = {451-452}, pmid = {35637413}, issn = {1759-5037}, mesh = {Adrenal Glands ; *COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {The symptoms of long COVID and chronic adrenal insufficiency have striking similarities. Therefore, we aim to raise awareness of assessing adrenal function in patients with long COVID.}, } @article {pmid35636906, year = {2022}, author = {Hope, AA and Evering, TH}, title = {Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.}, journal = {Infectious disease clinics of North America}, volume = {36}, number = {2}, pages = {379-395}, pmid = {35636906}, issn = {1557-9824}, support = {K01 HL140279/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or long coronavirus disease (COVID) is an emerging syndrome characterized by multiple persisting or newly emergent symptoms following the acute phase of SARS-CoV-2 infection. For affected patients, these prolonged symptoms can have a relapsing and remitting course and may be associated with disability and frequent health care utilization. Although many symptom-driven treatments are available, management remains challenging and often requires a multidisciplinary approach. This article summarizes the emerging consensus on definitions, epidemiology, and pathophysiology of long COVID and discusses what is understood about prevention, evaluation, and treatment of this syndrome.}, } @article {pmid35636457, year = {2022}, author = {Rohner, M and Schwarz, PEH and Bornstein, SR}, title = {Treating Insulin Resistance with Intermittent Personalized Nutrition to Sustain Metabolic Health and Functioning Immune System for Risk Reduction of Viral Diseases Especially COVID-19 and Long-COVID.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {54}, number = {8}, pages = {567-570}, doi = {10.1055/a-1864-8234}, pmid = {35636457}, issn = {1439-4286}, mesh = {*COVID-19/complications ; *Diabetes Mellitus, Type 2/complications/therapy ; Humans ; Immune System ; *Insulin Resistance ; Pandemics ; Risk Reduction Behavior ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The Covid-19 pandemic has provided new and strong evidence for poor outcomes of viral infection in patients with poor metabolic health. Insulin resistance is at the root of many metabolic conditions and a key driver of their progression as it promotes ineffectual inflammation whilst impairing immune functions. In a vicious circle, insulin resistance facilitates SARS-CoV-2 infection, whilst infection drives insulin resistance. We discuss the underlying mechanisms and explore ways to improve metabolic health and prevent insulin resistance through early detection and targeted nutritional interventions. With proven efficacy in prediabetes, type 2 diabetes, and their cardiovascular and organ complications, as much as non-alcoholic liver disease, we argue to extend such approaches to ensure resilience to the current pandemic and viral challenges beyond.}, } @article {pmid35635529, year = {2024}, author = {Nouraeinejad, A}, title = {A proposal to apply brain injury recovery treatments for cognitive impairment in COVID-19 survivors.}, journal = {The International journal of neuroscience}, volume = {134}, number = {1}, pages = {88-89}, doi = {10.1080/00207454.2022.2084091}, pmid = {35635529}, issn = {1563-5279}, mesh = {Humans ; *COVID-19/complications ; *Cognitive Dysfunction/etiology ; *Brain Injuries ; Survivors ; }, abstract = {There is still little information about the nature and broader prevalence of cognitive problems during post-infection in COVID-19 survivors. This is also the case for pathobiological findings related to these complications. In the meantime, there is mounting alarm regarding potential long-term outcomes of COVID-19, with descriptions of 'long COVID' symptoms keeping up into the chronic stage, which include 'brain fog'. The cognitive impairment or brain fog creates many difficulties in daily activities and makes problems for those who wish to successfully return to their job. The author proposes applying brain injury recovery treatments for cognitive impairment in COVID-19 survivors.}, } @article {pmid35633949, year = {2022}, author = {Izquierdo-Pujol, J and Moron-Lopez, S and Dalmau, J and Gonzalez-Aumatell, A and Carreras-Abad, C and Mendez, M and Rodrigo, C and Martinez-Picado, J}, title = {Post COVID-19 Condition in Children and Adolescents: An Emerging Problem.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {894204}, pmid = {35633949}, issn = {2296-2360}, abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.}, } @article {pmid35633158, year = {2022}, author = {Ahmad, SJ and Feigen, CM and Vazquez, JP and Kobets, AJ and Altschul, DJ}, title = {Neurological Sequelae of COVID-19.}, journal = {Journal of integrative neuroscience}, volume = {21}, number = {3}, pages = {77}, doi = {10.31083/j.jin2103077}, pmid = {35633158}, issn = {0219-6352}, mesh = {Anosmia/virology ; *COVID-19/complications ; Cytokines ; Disease Progression ; Encephalitis/virology ; Headache/virology ; Hemorrhagic Stroke/virology ; Humans ; Inflammation ; *Nervous System Diseases/virology ; SARS-CoV-2 ; Stroke/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders.

OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments.

METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients.

RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.}, } @article {pmid35632784, year = {2022}, author = {Sabino, JS and Amorim, MR and de Souza, WM and Marega, LF and Mofatto, LS and Toledo-Teixeira, DA and Forato, J and Stabeli, RG and Costa, ML and Spilki, FR and Sabino, EC and Faria, NR and Benites, BD and Addas-Carvalho, M and Stucchi, RSB and Vasconcelos, DM and Weaver, SC and Granja, F and Proenca-Modena, JL and Vilela, MMDS}, title = {Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report.}, journal = {Viruses}, volume = {14}, number = {5}, pages = {}, pmid = {35632784}, issn = {1999-4915}, support = {MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; MR/S019510/1/MRC_/Medical Research Council/United Kingdom ; R24 AI120942/AI/NIAID NIH HHS/United States ; MR/S0195/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Antibodies, Viral ; *COVID-19/complications ; Eating ; Female ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Milk, Human ; NF-kappa B ; RNA, Viral ; *SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.}, } @article {pmid35632776, year = {2022}, author = {Acanfora, D and Nolano, M and Acanfora, C and Colella, C and Provitera, V and Caporaso, G and Rodolico, GR and Bortone, AS and Galasso, G and Casucci, G}, title = {Impaired Vagal Activity in Long-COVID-19 Patients.}, journal = {Viruses}, volume = {14}, number = {5}, pages = {}, pmid = {35632776}, issn = {1999-4915}, mesh = {*COVID-19/complications ; Electrocardiography ; Heart Rate/physiology ; Humans ; *Primary Dysautonomias ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.}, } @article {pmid35632761, year = {2022}, author = {Seehusen, F and Clark, JJ and Sharma, P and Bentley, EG and Kirby, A and Subramaniam, K and Wunderlin-Giuliani, S and Hughes, GL and Patterson, EI and Michael, BD and Owen, A and Hiscox, JA and Stewart, JP and Kipar, A}, title = {Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse.}, journal = {Viruses}, volume = {14}, number = {5}, pages = {}, pmid = {35632761}, issn = {1999-4915}, support = {MR/W005611/1/MRC_/Medical Research Council/United Kingdom ; MR/T028750/1/MRC_/Medical Research Council/United Kingdom ; MR/V007181//1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/V03605X/1/MRC_/Medical Research Council/United Kingdom ; MR/V007181/1/MRC_/Medical Research Council/United Kingdom ; 75F40120C00085/FD/FDA HHS/United States ; ISSF201902/3/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Angiotensin-Converting Enzyme 2/genetics ; Animals ; *COVID-19/complications ; *Central Nervous System/physiopathology/virology ; Humans ; Mice ; Mice, Transgenic ; SARS-CoV-2/genetics ; *Viral Tropism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS.}, } @article {pmid35632649, year = {2022}, author = {Imai, K and Yamano, T and Nishi, S and Nishi, R and Nishi, T and Tanaka, H and Tsunoda, T and Yoshimoto, S and Tanaka, A and Hiromatsu, K and Shirasawa, S and Nakagawa, T and Nishi, K}, title = {Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment.}, journal = {Viruses}, volume = {14}, number = {5}, pages = {}, pmid = {35632649}, issn = {1999-4915}, mesh = {Adult ; *COVID-19/complications/therapy ; *Fatigue Syndrome, Chronic ; Headache ; Humans ; Inflammation ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.}, } @article {pmid35632408, year = {2022}, author = {Strain, WD and Sherwood, O and Banerjee, A and Van der Togt, V and Hishmeh, L and Rossman, J}, title = {The Impact of COVID Vaccination on Symptoms of Long COVID: An International Survey of People with Lived Experience of Long COVID.}, journal = {Vaccines}, volume = {10}, number = {5}, pages = {}, pmid = {35632408}, issn = {2076-393X}, abstract = {UNLABELLED: Long COVID is a multi-system syndrome following SARS-CoV-2 infection with persistent symptoms of at least 4 weeks, and frequently for several months. It has been suggested that there may be an autoimmune component. There has been an understandable caution amongst some people experiencing long COVID that, by boosting their immune response, a COVID vaccine may exacerbate their symptoms. We aimed to survey people living with long COVID, evaluating the impact of their first COVID vaccination on their symptoms.

METHODS: Patients with long COVID were invited to complete a web-based questionnaire through postings on social media and direct mailing from support groups. Basic demographics, range and severity of long COVID symptoms, before and after their vaccine, were surveyed.

RESULTS: 900 people participated in the questionnaire, of whom 45 had pre-existing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) but no evidence of COVID infection, and a further 43 did not complete the survey in full. The demographics and symptomology of the remaining 812 people were similar to those recorded by the UK Office of National Statistics. Following vaccination, 57.9% of participants reported improvements in symptoms, 17.9% reported deterioration and the remainder no change. There was considerable individual variation in responses. Larger improvements in symptom severity scores were seen in those receiving the mRNA vaccines compared to adenoviral vector vaccines.

CONCLUSIONS: Our survey suggests COVID-19 vaccination may improve long COVID patients, on average. The observational nature of the survey limits drawing direct causal inference, but requires validation with a randomised controlled trial.}, } @article {pmid35631077, year = {2022}, author = {Pérez-Gómez, HR and Morfín-Otero, R and González-Díaz, E and Esparza-Ahumada, S and León-Garnica, G and Rodríguez-Noriega, E}, title = {The Multifaceted Manifestations of Multisystem Inflammatory Syndrome during the SARS-CoV-2 Pandemic.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35631077}, issn = {2076-0817}, abstract = {The novel coronavirus SARS-CoV-2, which has similarities to the 2002-2003 severe acute respiratory syndrome coronavirus known as SARS-CoV-1, causes the infectious disease designated COVID-19 by the World Health Organization (Coronavirus Disease 2019). Although the first reports indicated that activity of the virus is centered in the lungs, it was soon acknowledged that SARS-CoV-2 causes a multisystem disease. Indeed, this new pathogen causes a variety of syndromes, including asymptomatic disease; mild disease; moderate disease; a severe form that requires hospitalization, intensive care, and mechanical ventilation; multisystem inflammatory disease; and a condition called long COVID or postacute sequelae of SARS-CoV-2 infection. Some of these syndromes resemble previously described disorders, including those with no confirmed etiology, such as Kawasaki disease. After recognition of a distinct multisystem inflammatory syndrome in children, followed by a similar syndrome in adults, various multisystem syndromes occurring during the pandemic associated or related to SARS-CoV-2 began to be identified. A typical pattern of cytokine and chemokine dysregulation occurs in these complex syndromes; however, the disorders have distinct immunological determinants that may help to differentiate them. This review discusses the origins of the different trajectories of the inflammatory syndromes related to SARS-CoV-2 infection.}, } @article {pmid35629421, year = {2022}, author = {Ylikoski, J and Lehtimäki, J and Pääkkönen, R and Mäkitie, A}, title = {Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {35629421}, issn = {2075-1729}, abstract = {Most SARS CoV-2 infections probably occur unnoticed or cause only cause a mild common cold that does not require medical intervention. A significant proportion of more severe cases is characterized by early neurological symptoms such as headache, fatigue, and impaired consciousness, including respiratory distress. These symptoms suggest hypoxia, specifically affecting the brain. The condition is best explained by primary replication of the virus in the nasal respiratory and/or the olfactory epithelia, followed by an invasion of the virus into the central nervous system, including the respiratory centers, either along a transneural route, through disruption of the blood-brain barrier, or both. In patients, presenting with early dyspnea, the primary goal of therapy should be the reversal of brain hypoxia as efficiently as possible. The first approach should be intermittent treatment with 100% oxygen using a tight oronasal mask or a hood. If this does not help within a few hours, an enclosure is needed to increase the ambient pressure. This management approach is well established in the hypoxia-related diseases in diving and aerospace medicine and preserves the patient's spontaneous breathing. Preliminary research evidence indicates that even a small elevation of the ambient pressure might be lifesaving. Other neurological symptoms, presenting particularly in long COVID-19, suggest imbalance of the autonomous nervous system, i.e., dysautonomia. These patients could benefit from vagal nerve stimulation.}, } @article {pmid35627801, year = {2022}, author = {Piras, I and Piazza, MF and Piccolo, C and Azara, A and Piana, A and Finco, G and Galletta, M}, title = {Experiences, Emotions, and Health Consequences among COVID-19 Survivors after Intensive Care Unit Hospitalization.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {10}, pages = {}, pmid = {35627801}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology ; Emotions ; Female ; Hospitalization ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Quality of Life ; Survivors/psychology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Literature suggested that COVID-19 patients experienced hospitalization as a physically and psychologically stressful event, with the risk to develop post-traumatic stress symptoms. The study aimed to understand psychological experiences of COVID-19 survivors with severe complications during and after ICU hospitalization, and any relevant health consequences. From October 2020 to January 2021, a qualitative study was conducted in Italy via semi-structured interviews by phone or video call addressed to COVID-19 survivors, randomly enrolled among people who released their stories publicly on newspapers, television, or social media. Fifteen individuals (three women and twelve men with average age of 56.4 years) were interviewed. Four main themes emerged: (i) emotion of fear; (ii) isolation and loneliness; (iii) unawareness about the gravity of the situation as a protective factor; (iv) "Long COVID" as consequences of the disease on physical and psychological health. During hospitalization, 66.7% of participants had mild or moderate values of anxiety and depression. After discharge, 86.7% moved to normal values. The results suggest that long-COVID is an important problem to manage to improve patients' quality of life. It is essential to guarantee a holistic take in charge starting before the discharge and continuing care after discharge in the community where they live.}, } @article {pmid35627530, year = {2022}, author = {Merzon, E and Weiss, M and Krone, B and Cohen, S and Ilani, G and Vinker, S and Cohen-Golan, A and Green, I and Israel, A and Schneider, T and Ashkenazi, S and Weizman, A and Manor, I}, title = {Clinical and Socio-Demographic Variables Associated with the Diagnosis of Long COVID Syndrome in Youth: A Population-Based Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {10}, pages = {}, pmid = {35627530}, issn = {1660-4601}, mesh = {Adolescent ; *Attention Deficit Disorder with Hyperactivity/complications ; *COVID-19/complications/diagnosis/epidemiology ; Child ; Humans ; Morbidity ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {This study examines the demographic, clinical and socioeconomic factors associated with diagnosis of long COVID syndrome (LCS). Data of 20,601 COVID-19-positive children aged 5 to 18 years were collected between 2020 and 2021 in an Israeli database. Logistic regression analysis was used to evaluate the adjusted odds ratio for the characteristics of the COVID-19 infection and pre-COVID-19 morbidities. Children with LCS were significantly more likely to have been severely symptomatic, required hospitalization, and experienced recurrent acute infection within 180 days. In addition, children with LCS were significantly more likely to have had ADHD, chronic urticaria, and allergic rhinitis. Diagnosis of LCS is significantly associated with pre-COVID-19 ADHD diagnosis, suggesting clinicians treating ADHD children who become infected with COVID-19 remain vigilant for the possibility of LCS. Although the risk of severe COVID-19 infection and LCS in children is low, further research on possible morbidity related to LCS in children is needed.}, } @article {pmid35627510, year = {2022}, author = {Laestadius, LI and Guidry, JPD and Bishop, A and Campos-Castillo, C}, title = {State Health Department Communication about Long COVID in the United States on Facebook: Risks, Prevention, and Support.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {10}, pages = {}, pmid = {35627510}, issn = {1660-4601}, mesh = {*COVID-19/complications/epidemiology/prevention & control ; *Health Communication ; Humans ; *Social Media ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Greater public awareness of long COVID severity and susceptibility is needed to support those with long COVID and encourage preventive behaviors. It is not yet known to what extent health departments have informed the public about long COVID risks or offered guidance and support for those with long COVID. The objective of this research was to determine how and to what extent US state health departments have communicated with the public about long COVID via Facebook. Facebook posts with COVID-19 and long COVID terms made by 50 US state health departments plus Washington, DC, from 1 January 2020 to 31 January 2022, were collected using CrowdTangle. The first long COVID post appeared on 15 July 2020. From 15 July 2020 to 31 January 2022, state health departments made 49,310 COVID-19 posts and 137 long COVID posts. Using quantitative content analysis methods, long COVID posts were coded for health belief model constructs. Among long COVID posts, 75.18% included language about susceptibility, 64.96% severity, and 64.23% benefits of prevention. Cues to preventive action appeared in 54.01% of posts. 19.71% of posts provided guidance for those with long COVID. While health departments posted extensively about COVID-19, posts about long COVID were rare. This represents a missed opportunity to bolster arguments for preventive behaviors and support those experiencing long COVID.}, } @article {pmid35627472, year = {2022}, author = {Wose Kinge, C and Hanekom, S and Lupton-Smith, A and Akpan, F and Mothibi, E and Maotoe, T and Lebatie, F and Majuba, P and Sanne, I and Chasela, C}, title = {Persistent Symptoms among Frontline Health Workers Post-Acute COVID-19 Infection.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {10}, pages = {}, pmid = {35627472}, issn = {1660-4601}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Female ; Health Personnel ; Health Workforce ; Humans ; Male ; Post-Acute COVID-19 Syndrome ; }, abstract = {Growing evidence shows that a significant number of patients with COVID-19 experience persistent symptoms, also known as long COVID-19. We sought to identify persistent symptoms of COVID-19 in frontline workers at Right to Care South Africa, who are past the acute phase of illness, using a cross-sectional survey. We analysed data from 207 eligible COVID-19 positive frontline workers who participated in a two-month post-COVID-19 online self-administered survey. The survey response rate was 30%; of the 62 respondents with a median age of 33.5 years (IQR= 30-44 years), 47 (76%) were females. The majority (n = 55; 88.7%) self-isolated and 7 (11.3%) were admitted to hospital at the time of diagnosis. The most common comorbid condition reported was hypertension, particularly among workers aged 45-55 years. The most reported persistent symptoms were characterised by fatigue, anxiety, difficulty sleeping, chest pain, muscle pain, and brain fog. Long COVID-19 is a serious phenomenon, of which much is still unknown, including its causes, how common it is especially in non-hospitalised healthcare workers, and how to treat it. Given the rise in COVID-19 cases, the prevalence of long COVID-19 is likely to be substantial; thus, the need for rehabilitation programs targeted at each persistent COVID-19 symptom is critical.}, } @article {pmid35626317, year = {2022}, author = {Petrella, C and Nenna, R and Petrarca, L and Tarani, F and Paparella, R and Mancino, E and Di Mattia, G and Conti, MG and Matera, L and Bonci, E and Ceci, FM and Ferraguti, G and Gabanella, F and Barbato, C and Di Certo, MG and Cavalcanti, L and Minni, A and Midulla, F and Tarani, L and Fiore, M}, title = {Serum NGF and BDNF in Long-COVID-19 Adolescents: A Pilot Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {35626317}, issn = {2075-4418}, abstract = {COVID-19 (COronaVIrus Disease 19) is an infectious disease also known as an acute respiratory syndrome caused by the SARS-CoV-2. Although in children and adolescents SARS-CoV-2 infection produces mostly mild or moderate symptoms, in a certain percentage of recovered young people a condition of malaise, defined as long-COVID-19, remains. To date, the risk factors for the development of long-COVID-19 are not completely elucidated. Neurotrophins such as NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) are known to regulate not only neuronal growth, survival and plasticity, but also to influence cardiovascular, immune, and endocrine systems in physiological and/or pathological conditions; to date only a few papers have discussed their potential role in COVID-19. In the present pilot study, we aimed to identify NGF and BDNF changes in the serum of a small cohort of male and female adolescents that contracted the infection during the second wave of the pandemic (between September and October 2020), notably in the absence of available vaccines. Blood withdrawal was carried out when the recruited adolescents tested negative for the SARS-CoV-2 ("post-infected COVID-19"), 30 to 35 days after the last molecular test. According to their COVID-19 related outcomes, the recruited individuals were divided into three groups: asymptomatics, acute symptomatics and symptomatics that over time developed long-COVID-19 symptoms ("future long-COVID-19"). As a control group, we analyzed the serum of age-matched healthy controls that did not contract the infection. Inflammatory biomarkers (TNF-α, TGF-β), MCP-1, IL-1α, IL-2, IL-6, IL-10, IL-12) were also analyzed with the free oxygen radicals' presence as an oxidative stress index. We showed that NGF serum content was lower in post-infected-COVID-19 individuals when compared to healthy controls; BDNF levels were found to be higher compared to healthy individuals only in post-infected-COVID-19 symptomatic and future long-COVID-19 girls, leaving the BDNF levels unchanged in asymptomatic individuals if compared to controls. Oxidative stress and inflammatory biomarkers were unchanged in male and female adolescents, except for TGF-β that, similarly to BDNF, was higher in post-infected-COVID-19 symptomatic and future long-COVID-19 girls. We predicted that NGF and/or BDNF could be used as early biomarkers of COVID-19 morbidity in adolescents.}, } @article {pmid35624973, year = {2022}, author = {Nowakowski, S and Kokonda, M and Sultana, R and Duong, BB and Nagy, SE and Zaidan, MF and Baig, MM and Grigg, BV and Seashore, J and Deer, RR}, title = {Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic.}, journal = {Brain sciences}, volume = {12}, number = {5}, pages = {}, pmid = {35624973}, issn = {2076-3425}, support = {R01NR018342;/NH/NIH HHS/United States ; P30AG024832/NH/NIH HHS/United States ; R01 NR018342/NR/NINR NIH HHS/United States ; UL1TR001439/NH/NIH HHS/United States ; P30 AG024832/AG/NIA NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; }, abstract = {A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time.}, } @article {pmid35624901, year = {2022}, author = {Savino, R and Polito, AN and Arcidiacono, G and Poliseno, M and Lo Caputo, S}, title = {Neuropsychiatric Disorders in Pediatric Long COVID-19: A Case Series.}, journal = {Brain sciences}, volume = {12}, number = {5}, pages = {}, pmid = {35624901}, issn = {2076-3425}, abstract = {Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection.}, } @article {pmid35624818, year = {2022}, author = {Ercegovac, M and Asanin, M and Savic-Radojevic, A and Ranin, J and Matic, M and Djukic, T and Coric, V and Jerotic, D and Todorovic, N and Milosevic, I and Stevanovic, G and Simic, T and Bukumiric, Z and Pljesa-Ercegovac, M}, title = {Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35624818}, issn = {2076-3921}, support = {7546803, entitled AntioxIdentification//Science Fund of the Republic of Serbia, Special Research Program on COVID-19/ ; }, abstract = {Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.}, } @article {pmid35623871, year = {2022}, author = {Quilliot, D}, title = {Overweight subjects have a higher risk of malnutrition and loss of function after severe COVID infection.}, journal = {Clinical nutrition ESPEN}, volume = {49}, number = {}, pages = {669-670}, pmid = {35623871}, issn = {2405-4577}, mesh = {*COVID-19 ; Humans ; *Malnutrition/complications/epidemiology ; Overweight/complications ; }, } @article {pmid35619573, year = {2022}, author = {Kim, Y and Kim, SW and Chang, HH and Kwon, KT and Hwang, S and Bae, S}, title = {One Year Follow-Up of COVID-19 Related Symptoms and Patient Quality of Life: A Prospective Cohort Study.}, journal = {Yonsei medical journal}, volume = {63}, number = {6}, pages = {499-510}, pmid = {35619573}, issn = {1976-2437}, support = {2020-ER5334-00//Korea Centers for Disease Control and Prevention/Republic of Korea ; 2021-ER1901-00//Korea Centers for Disease Control and Prevention/Republic of Korea ; }, mesh = {Adult ; Anxiety Disorders/diagnosis ; *COVID-19 ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Quality of Life/psychology ; }, abstract = {PURPOSE: Globally, concerns have grown regarding the long-term effects of novel coronavirus disease (COVID-19) infection. Therefore, we evaluated the long-term course of persistent symptoms and patient quality of life.

MATERIALS AND METHODS: This prospective cohort study was conducted at a single tertiary university hospital from August 31, 2020 to March 29, 2021 with adult patients followed at 6 and 12 months after acute COVID-19 symptom onset or diagnosis. Clinical characteristics, self-reported symptoms, EuroQol 5 dimension 5 level (EQ5D-5L) index scores, Korean version of the Patient Health Questionnaire-9 (PHQ-9), Korean version of the Posttraumatic Stress Disorder Checklist-5 (PCL-5-K), and Generalized Anxiety Disorder-7 (GAD-7) were investigated. Symptom persistent or non-persistent groups were defined according to persistency of COVID-19 related symptoms or signs after acute COVID-19 infection, respectively.

RESULTS: Of all 235 patients, 170 (64.6%) patients were eligible for analysis. The median age was 51 (interquartile range, 37-61) years old, and 102 patients were female (60.0%). After 12 months from acute COVID-19 infection, in total, 83 (48.8%) patients still suffered from COVID-19-related symptoms. The most common symptoms included amnesia (24.1%), insomnia (14.7%), fatigue (13.5%), and anxiety (12.9%). Among the five EQ5D-5L categories, the average value of anxiety or depression was the most predominant. PHQ-9 and PCL-5-K scores were statistically higher in the COVID-19-related symptom persistent group than the non-persistent group (p=0.001). However, GAD-7 scores showed no statistical differences between the two groups (p=0.051).

CONCLUSION: Neuropsychiatric symptoms were the major COVID-19-related symptoms after 12 months from acute COVID-19 infection, reducing quality of life.}, } @article {pmid35618472, year = {2022}, author = {Jenkins, H}, title = {Recommendations for the recognition, diagnosis, and management of long COVID.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {719}, pages = {259}, pmid = {35618472}, issn = {1478-5242}, mesh = {*COVID-19/complications/diagnosis/therapy ; Delphi Technique ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35618462, year = {2022}, author = {Chew-Graham, CA and Briggs, TA and Kane, B}, title = {Long COVID in children and young people: uncertainty and contradictions.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {719}, pages = {253-254}, pmid = {35618462}, issn = {1478-5242}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35618461, year = {2022}, author = {Bovo, MV and Launer, J}, title = {'Tell me about that colleague': long COVID, narrative medicine, and a remarkable conversation.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {719}, pages = {278-279}, pmid = {35618461}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Communication ; Humans ; Narration ; *Narrative Medicine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35615791, year = {2023}, author = {Murch, BJ and Hollier, SE and Kenward, C and Wood, RM}, title = {Use of linked patient data to assess the effect of Long-COVID on system-wide healthcare utilisation.}, journal = {Health information management : journal of the Health Information Management Association of Australia}, volume = {52}, number = {3}, pages = {167-175}, doi = {10.1177/18333583221089915}, pmid = {35615791}, issn = {1833-3575}, mesh = {Male ; Female ; Humans ; *Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Testing ; Semantic Web ; *COVID-19/epidemiology ; Delivery of Health Care ; Patient Acceptance of Health Care ; }, abstract = {Background: Within the relatively early stages of the COVID-19 pandemic, there had been an awareness of the potential longer-term effects of infection (so called Long-COVID) but little was known of the ongoing demands such patients may place on healthcare services. Objective: To investigate whether COVID-19 illness is associated with increased post-acute healthcare utilisation. Method: Using linked data from primary care, secondary care, mental health and community services, activity volumes were compared across the 3 months preceding and proceeding COVID-19 diagnoses for 7,791 individuals, with a distinction made between whether or not patients were hospitalised for treatment. Differences were assessed against those of a control group containing individuals who had not received a COVID-19 diagnosis. All data were sourced from the authors' healthcare system in South West England. Results: For hospitalised COVID-19 cases, a statistically significant increase in non-elective admissions was identified for males and females <65 years. For non-hospitalised cases, statistically significant increases were identified in GP Doctor and Nurse attendances and GP prescriptions (males and females, all ages); Emergency Department attendances (females <65 years); Mental Health contacts (males and females ≥65 years); and Outpatient consultations (males ≥65 years). Conclusion: There is evidence of an association between positive COVID-19 diagnosis and increased post-acute activity within particular healthcare settings. Linked patient-level data provides information that can be useful to understand ongoing healthcare needs resulting from Long-COVID, and support the configuration of Long-COVID pathways of care.}, } @article {pmid35615437, year = {2022}, author = {O'Doherty, L and Hendricken Phelan, S and Wood, N and O'Brien, S and Sui, J and Mangan, C and Howley, F and O'Regan, S and Razif, NAM and Conlan, C and Argue, R and Holohan, S and Dyer, A and Salleh, F and Townsend, L and Hughes, G and Kerr, C and Reidy, D and Sanz, A and Connolly, E and Kelly, A and Leacy, E and Reddy, C and Gargan, S and Breen, E and Hawerkamp, H and Dunne, J and Martin-Loeches, I and McLaughlin, AM and Long, A and Shiels, O and Fallon, P and Hennessy, M and Romero-Ortuno, R and Bannan, C and Prior, AR and Rakovac, A and McCormack, W and McManus, R and Donnelly, S and Bergin, C and Little, M and Ní Cheallaigh, C and Conlon, N}, title = {Study protocol for the St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19.}, journal = {HRB open research}, volume = {5}, number = {}, pages = {20}, pmid = {35615437}, issn = {2515-4826}, abstract = {Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited. Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.}, } @article {pmid35614263, year = {2022}, author = {Reardon, S}, title = {Long COVID risk falls only slightly after vaccination, huge study shows.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {35614263}, issn = {1476-4687}, } @article {pmid35614233, year = {2022}, author = {Al-Aly, Z and Bowe, B and Xie, Y}, title = {Long COVID after breakthrough SARS-CoV-2 infection.}, journal = {Nature medicine}, volume = {28}, number = {7}, pages = {1461-1467}, pmid = {35614233}, issn = {1546-170X}, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; Humans ; *Nervous System Diseases ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-also referred to as Long COVID-have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.}, } @article {pmid35614173, year = {2022}, author = {El Otmani, H and Nabili, S and Berrada, M and Bellakhdar, S and El Moutawakil, B and Abdoh Rafai, M}, title = {Prevalence, characteristics and risk factors in a Moroccan cohort of Long-Covid-19.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {9}, pages = {5175-5180}, pmid = {35614173}, issn = {1590-3478}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Morocco/epidemiology ; Prevalence ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Covid-19 can involve persistence of nonspecific symptoms and sequelae that last weeks to months after initial recovery, but the definition of this situation is lacking. Thus, the aim of our study is to estimate the prevalence, symptoms, and signs extending beyond the acute phase of Covid-19 compared to the general population not infected with the virus and to assess the factors influencing the occurrence of these symptoms in developing countries like Morocco.

PATIENTS AND METHODS: This study recruited 118 healthcare workers who endured the Covid-19 infection and 118 matched controls that had never experienced it. We have defined Long-Covid-19 according to guidance for NICE, and we used a survey made of direct questions and short answers sent to the recruiters via mail to evaluate the demographic parameters, severity and duration of the Covid-19 symptoms, vaccination against SARS CoV-2, and pulmonary involvement, and a series of general symptoms were looked for.

FINDINGS: Our study found that the prevalence of Long-Covid-19 was 47.4%. Compared to the general population, the symptoms with statistical significative results were predominated by asthenia, myalgia, and brain fog. The severity of the pulmonary involvement on chest CT scan was the only risk factor to their occurrence, whereas no effect of the vaccination anti-SARS-CoV-2 was found.

CONCLUSION: Comparing to the literature, this study showed that nearly half of the patients who have been infected with SARS-CoV-2 will experience a variety of symptoms after the acute phase of this infection, and that it would be a real burden even in the youngest. We also found that vaccination against SARS-Cov-2 has no impact on this prevalence, which is to the best of our knowledge has never been previously studied.}, } @article {pmid35614108, year = {2022}, author = {Kersten, J and Wolf, A and Hoyo, L and Hüll, E and Tadic, M and Andreß, S and d'Almeida, S and Scharnbeck, D and Roder, E and Beschoner, P and Rottbauer, W and Buckert, D}, title = {Symptom burden correlates to impairment of diffusion capacity and exercise intolerance in long COVID patients.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8801}, pmid = {35614108}, issn = {2045-2322}, mesh = {*COVID-19/complications ; Exercise Tolerance ; Female ; Humans ; Lung ; Male ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {After acute infection with the SARS-CoV-2 virus, a considerable number of patients remains symptomatic with pathological changes in various organ systems. This study aimed to relate the physical and mental burden of symptoms of long COVID patients to the findings of a somatic evaluation. In patients with persistent long COVID symptoms three months after acute infection we assessed physical and mental health status using the SF-36 questionnaire. The cohort was dichotomised by the results (upper two quartiles vs. lower to quartiles) and compared with regard to transthoracic echocardiography, body plethysmography (including diffusion capacity), capillary blood gas analysis and 6-min walk test (6-MWT). From February 22 to September 13, 2021, 463 patients were prospectively examined, of which 367 completed the SF-36 questionnaire. A positive correlation between initial disease severity (need for hospitalization, intensive care medicine) and resulting symptom burden at follow-up could be demonstrated. Patients with impaired subjective physical and mental status were significantly more likely to be women. There was a significant correlation between symptom severity and reduced exercise tolerance in the 6-MWT (495.6 ± 83.7 m vs 549.7 ± 71.6 m, p < 0.001) and diffusion capacity for carbon monoxide (85.6 ± 14.3% of target vs 94.5 ± 14.4, p < 0.001). In long COVID patients, initial disease severity is correlated with symptom burden after at least 3 months of follow-up. Highly symptomatic long COVID patients show impaired diffusion capacity and 6-MWT despite average or mildly affected mechanical lung parameters. It must be further differentiated whether this corresponds to a transient functional impairment or whether it is a matter of defined organ damage.}, } @article {pmid35610313, year = {2022}, author = {Frere, JJ and tenOever, BR}, title = {Cardiometabolic syndrome - an emergent feature of Long COVID?.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {7}, pages = {399-400}, pmid = {35610313}, issn = {1474-1741}, mesh = {*COVID-19/complications ; *Cardiovascular Diseases ; Humans ; *Metabolic Syndrome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Large-scale clinical studies on the post-infectious impacts of SARS-CoV-2 have suggested that patients who have recovered from acute infection have increased risk for cardiometabolic syndrome-associated morbidities such as diabetes, chronic kidney disease and heart failure. Initial studies have taken the first steps towards unravelling the molecular processes that may be driving these findings, including the role of immune and inflammatory factors, but a comprehensive aetiology remains unclear. Given that cardiometabolic syndrome progression in patients with Long COVID may pose a significant global health and economic burden post pandemic, there is an emergent need to identify therapeutic targets and treatment options.}, } @article {pmid35608715, year = {2023}, author = {Al-Kuraishy, HM and Al-Gareeb, AI and El-Bouseary, MM and Sonbol, FI and Batiha, GE}, title = {Hyperviscosity syndrome in COVID-19 and related vaccines: exploring of uncertainties.}, journal = {Clinical and experimental medicine}, volume = {23}, number = {3}, pages = {679-688}, pmid = {35608715}, issn = {1591-9528}, mesh = {Humans ; COVID-19 Vaccines/adverse effects ; Post-Acute COVID-19 Syndrome ; Prospective Studies ; *COVID-19/prevention & control ; Immunoglobulins ; *Vaccines ; *Immune System Diseases ; Vaccination ; Fibrinogen ; }, abstract = {Hyperviscosity syndrome (HVS) recently emerged as a complication of coronavirus disease 2019 (COVID-19) and COVID-19 vaccines. Therefore, the objectives of this critical review are to establish the association between COVID-19 and COVID-19 vaccines with the development of HVS. HVS may develop in various viral infections due to impairment of humoral and cellular immunity with elevation of immunoglobulins. COVID-19 can increase blood viscosity (BV) through modulation of fibrinogen, albumin, lipoproteins, and red blood cell (RBC) indices. HVS can cause cardiovascular and neurological complications in COVID-19 like myocardial infarction (MI) and stroke. HVS with or without abnormal RBCs function in COVID-19 participates in the reduction of tissue oxygenation with the development of cardio-metabolic complications and long COVID-19. Besides, HVS may develop in vaccine recipients with previous COVID-19 due to higher underlying Ig concentrations and rarely without previous COVID-19. Similarly, patients with metabolic syndrome are at the highest risk for propagation of HVS after COVID-19 vaccination. In conclusion, COVID-19 and related vaccines are linked with the development of HVS, mainly in patients with previous COVID-19 and underlying metabolic derangements. The possible mechanism of HVS in COVID-19 and related vaccines is increasing levels of fibrinogen and immunoglobulins. However, dehydration, oxidative stress, and inflammatory reactions are regarded as additional contributing factors in the pathogenesis of HVS in COVID-19. However, this critical review cannot determine the final causal relationship between COVID-19 and related vaccines and the development of HVS. Prospective and retrospective studies are warranted in this field.}, } @article {pmid35608619, year = {2022}, author = {Schmoll, D}, title = {[Long COVID: what can the psychiatric expert use for support?].}, journal = {Der Nervenarzt}, volume = {93}, number = {7}, pages = {754}, pmid = {35608619}, issn = {1433-0407}, mesh = {*COVID-19/complications/psychology ; Humans ; Psychiatry ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35608443, year = {2022}, author = {Grist, JT and Collier, GJ and Walters, H and Kim, M and Chen, M and Abu Eid, G and Laws, A and Matthews, V and Jacob, K and Cross, S and Eves, A and Durrant, M and McIntyre, A and Thompson, R and Schulte, RF and Raman, B and Robbins, PA and Wild, JM and Fraser, E and Gleeson, F}, title = {Lung Abnormalities Detected with Hyperpolarized [129]Xe MRI in Patients with Long COVID.}, journal = {Radiology}, volume = {305}, number = {3}, pages = {709-717}, pmid = {35608443}, issn = {1527-1315}, support = {FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; SP/14/6/31350/BHF_/British Heart Foundation/United Kingdom ; MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Male ; Humans ; Female ; Adult ; Middle Aged ; *Xenon Isotopes ; *COVID-19/diagnostic imaging ; Prospective Studies ; Magnetic Resonance Imaging/methods ; Lung/diagnostic imaging ; Dyspnea ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background Post-COVID-19 condition encompasses symptoms following COVID-19 infection that linger at least 4 weeks after the end of active infection. Symptoms are wide ranging, but breathlessness is common. Purpose To determine if the previously described lung abnormalities seen on hyperpolarized (HP) pulmonary xenon 129 ([129]Xe) MRI scans in participants with post-COVID-19 condition who were hospitalized are also present in participants with post-COVID-19 condition who were not hospitalized. Materials and Methods In this prospective study, nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) were enrolled from June 2020 to August 2021. Participants underwent chest CT, HP [129]Xe MRI, pulmonary function testing, and the 1-minute sit-to-stand test and completed breathlessness questionnaires. Control subjects underwent HP [129]Xe MRI only. CT scans were analyzed for post-COVID-19 interstitial lung disease severity using a previously published scoring system and full-scale airway network (FAN) modeling. Analysis used group and pairwise comparisons between participants and control subjects and correlations between participant clinical and imaging data. Results A total of 11 NHLC participants (four men, seven women; mean age, 44 years ± 11 [SD]; 95% CI: 37, 50) and 12 PHC participants (10 men, two women; mean age, 58 years ±10; 95% CI: 52, 64) were included, with a significant difference in age between groups (P = .05). Mean time from infection was 287 days ± 79 (95% CI: 240, 334) and 143 days ± 72 (95% CI: 105, 190) in NHLC and PHC participants, respectively. NHLC and PHC participants had normal or near normal CT scans (mean, 0.3/25 ± 0.6 [95% CI: 0, 0.63] and 7/25 ± 5 [95% CI: 4, 10], respectively). Gas transfer (Dlco) was different between NHLC and PHC participants (mean Dlco, 76% ± 8 [95% CI: 73, 83] vs 86% ± 8 [95% CI: 80, 91], respectively; P = .04), but there was no evidence of other differences in lung function. Mean red blood cell-to-tissue plasma ratio was different between volunteers (mean, 0.45 ± 0.07; 95% CI: 0.43, 0.47]) and PHC participants (mean, 0.31 ± 0.10; 95% CI: 0.24, 0.37; P = .02) and between volunteers and NHLC participants (mean, 0.37 ± 0.10; 95% CI: 0.31, 0.44; P = .03) but not between NHLC and PHC participants (P = .26). FAN results did not correlate with Dlco) or HP [129]Xe MRI results. Conclusion Nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) showed hyperpolarized pulmonary xenon 129 MRI and red blood cell-to-tissue plasma abnormalities, with NHLC participants demonstrating lower gas transfer than PHC participants despite having normal CT findings. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Parraga and Matheson in this issue.}, } @article {pmid35608204, year = {2022}, author = {Ladlow, P and O'Sullivan, O and Bennett, AN and Barker-Davies, R and Houston, A and Chamley, R and May, S and Mills, D and Dewson, D and Rogers-Smith, K and Ward, C and Taylor, J and Mulae, J and Naylor, J and Nicol, ED and Holdsworth, DA}, title = {The effect of medium-term recovery status after COVID-19 illness on cardiopulmonary exercise capacity in a physically active adult population.}, journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, volume = {132}, number = {6}, pages = {1525-1535}, pmid = {35608204}, issn = {1522-1601}, support = {//Defense Medical Services Research Steering Group/ ; }, mesh = {Adult ; *COVID-19 ; Exercise Test ; Exercise Tolerance ; *Heart Failure ; Humans ; Oxygen ; Oxygen Consumption ; }, abstract = {A failure to fully recover following coronavirus disease 2019 (COVID-19) may have a profound impact on high-functioning populations ranging from frontline emergency services to professional or amateur/recreational athletes. The aim of the study is to describe the medium-term cardiopulmonary exercise profiles of individuals with "persistent symptoms" and individuals who feel "recovered" after hospitalization or mild-moderate community infection following COVID-19 to an age, sex, and job-role matched control group. A total of 113 participants underwent cardiopulmonary functional tests at a mean of 159 ± 7 days (∼5 mo) following acute illness; 27 hospitalized with persistent symptoms (hospitalized-symptomatic), 8 hospitalized and now recovered (hospitalized-recovered); 34 community managed with persistent symptoms (community-symptomatic); 18 community managed and now recovered (community-recovered); and 26 controls. Hospitalized groups had the least favorable body composition (body mass, body mass index, and waist circumference) compared with controls. Hospitalized-symptomatic and community-symptomatic individuals had a lower oxygen uptake (V̇o2) at peak exercise (hospitalized-symptomatic, 29.9 ± 5.0 mL/kg/min; community-symptomatic, 34.4 ± 7.2 mL/kg/min; vs. control 43.9 ± 3.1 mL/kg/min, both P < 0.001). Hospitalized-symptomatic individuals had a steeper V̇e/V̇co2 slope (lower ventilatory efficiency) (30.5 ± 5.3 vs. 25.5 ± 2.6, P = 0.003) versus. controls. Hospitalized-recovered had a significantly lower oxygen uptake at peak (32.6 ± 6.6 mL/kg/min vs. 43.9 ± 13.1 mL/kg/min, P = 0.015) compared with controls. No significant differences were reported between community-recovered individuals and controls in any cardiopulmonary parameter. In conclusion, medium-term findings suggest that community-recovered individuals did not differ in cardiopulmonary fitness from physically active healthy controls. This suggests their readiness to return to higher levels of physical activity. However, the hospitalized-recovered group and both groups with persistent symptoms had enduring functional limitations, warranting further monitoring, rehabilitation, and recovery.NEW & NOTEWORTHY At 5 mo postinfection, community-treated individuals who feel recovered have comparable cardiopulmonary exercise profiles to the physically trained and active controls, suggesting a readiness to return to higher intensity/volumes of exercise. However, both symptomatic groups and the hospital-recovered group have persistent functional limitations when compared with active controls, supporting the requirement for ongoing monitoring, rehabilitation, and recovery.}, } @article {pmid35606656, year = {2022}, author = {Hellwig, S and Domschke, K}, title = {[Post-COVID syndrome-Focus fatigue].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {788-796}, pmid = {35606656}, issn = {1433-0407}, mesh = {*COVID-19/complications/therapy ; Depression/therapy ; Fatigue/diagnosis/etiology/therapy ; *Fatigue Syndrome, Chronic/diagnosis/psychology/therapy ; Humans ; SARS-CoV-2 ; }, abstract = {The World Health Organization (WHO) defines post-coronavirus disease 2019 (COVID-19) as a condition which occurs in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection 3 months after the onset of COVID-19 symptoms, lasts for at least 2 months and cannot be explained by an alternative diagnosis. Core symptoms of post-COVID syndrome are fatigue, dyspnea and cognitive dysfunction, which have an impact on everyday functional level. Neuropsychiatric late sequelae are common in COVID-19 patients, with incidence rates over 30%. Beside the abovementioned core symptoms, sleep disorders, depression and anxiety show increased incidences. According to current opinion, associated neuropsychiatric symptoms are subsumed under the term post-COVID syndrome but are also interpreted as comorbidities, which can promote the manifestation of a post-COVID syndrome. The key symptom fatigue shows symptom overlapping and comorbidity with psychiatric disorders. Imaging studies indicate an organic correlate of fatigue in post-COVID patients. Furthermore, psychosocial aspects and psychiatric comorbidities, such as depression and anxiety disorders as modulating and therefore potentially treatable factors were identified. Treatment of fatigue consists of pharmacological management with stimulants and antidepressants as well as nonpharmacological strategies, most notably cognitive behavioral therapy and exercise-focused interventions. The evidence for this comes from meta-analyses of tumor-associated or post-viral fatigue.}, } @article {pmid35605170, year = {2022}, author = {Meza-Torres, B and Delanerolle, G and Okusi, C and Mayor, N and Anand, S and Macartney, J and Gatenby, P and Glampson, B and Chapman, M and Curcin, V and Mayer, E and Joy, M and Greenhalgh, T and Delaney, B and de Lusignan, S}, title = {Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.}, journal = {JMIR public health and surveillance}, volume = {8}, number = {8}, pages = {e37668}, pmid = {35605170}, issn = {2369-2960}, mesh = {Female ; Humans ; Male ; *COVID-19/complications ; *Cross Infection ; *Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Community-Acquired Infections ; }, abstract = {BACKGROUND: Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

OBJECTIVE: We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

METHODS: We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

RESULTS: In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

CONCLUSIONS: The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.}, } @article {pmid35603810, year = {2022}, author = {Sivan, M and Preston, N and Parkin, A and Makower, S and Gee, J and Ross, D and Tarrant, R and Davison, J and Halpin, S and O'Connor, RJ and Horton, M}, title = {The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) patient-reported outcome measure for Long Covid or Post-COVID-19 syndrome.}, journal = {Journal of medical virology}, volume = {94}, number = {9}, pages = {4253-4264}, pmid = {35603810}, issn = {1096-9071}, mesh = {*COVID-19/complications/diagnosis ; Humans ; Patient Reported Outcome Measures ; Reproducibility of Results ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The C19-YRS is the literature's first condition-specific, validated scale for patient assessment and monitoring in Post-COVID-19 syndrome (PCS). The 22-item scale's subscales (scores) are symptom severity (0-100), functional disability (0-50), additional symptoms (0-60), and overall health (0-10).

OBJECTIVES: This study aimed to test the scale's psychometric properties using Rasch analysis and modify the scale based on analysis findings, emerging information on essential PCS symptoms, and feedback from a working group of patients and professionals.

METHODS: Data from 370 PCS patients were assessed using a Rasch Measurement Theory framework to test model fit, local dependency, response category functioning, differential item functioning, targeting, reliability, and unidimensionality. The working group undertook iterative changes to the scale based on the psychometric results and including essential symptoms.

RESULTS: Symptom severity and functional disability subscales showed good targeting and reliability. Post hoc rescoring suggested that a 4-point response category structure would be more appropriate than an 11-point response for both subscales. Symptoms with binary responses were placed in the other symptoms subscale. The overall health single-item subscale remained unchanged.

CONCLUSION: A 17-item C19-YRSm was developed with subscales (scores): symptom severity (0-30), functional disability (0-15), other symptoms (0-25), and overall health (0-10).}, } @article {pmid35602927, year = {2022}, author = {Rolin, S and Chakales, A and Verduzco-Gutierrez, M}, title = {Rehabilitation Strategies for Cognitive and Neuropsychiatric Manifestations of COVID-19.}, journal = {Current physical medicine and rehabilitation reports}, volume = {10}, number = {3}, pages = {182-187}, pmid = {35602927}, issn = {2167-4833}, abstract = {PURPOSE OF REVIEW: Extrapulmonary manifestations of COVID-19 are abundant, including after recovery of acute SARS-CoV-2 infection. This review seeks to explore the cognitive and neuropsychiatric manifestations of COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), including Long COVID syndromes. Furthermore, the review will discuss rehabilitation strategies for the emerging neurological consequences of COVID-19 to help those experiencing long-term effects of COVID-19.

RECENT FINDINGS: There is emerging evidence depicting the neural involvement of COVID-19. Health priorities have shifted from understanding pathogenesis and treatment of pulmonary symptoms to targeting the acute and chronic sequelae of COVID-19, including cognitive and neuropsychiatric symptoms. The sequelae of COVID-19 often co-occur with other medical problems and is best managed by assessment and care across multiple disciplines. Symptoms following infection are similar to those found by other syndromes and disorders that disrupt the central nervous system.

SUMMARY: The acute and chronic sequelae of COVID-19 have become major targets of current health care providers given its significant public health impact, inclusive of cognitive and neuropsychiatric sequelae. Assessment and referral to rehabilitation based on each individual's needs and symptoms can decrease morbidity and improve quality of life.}, } @article {pmid35602198, year = {2021}, author = {Alwan, NA}, title = {The teachings of Long COVID.}, journal = {Communications medicine}, volume = {1}, number = {}, pages = {15}, pmid = {35602198}, issn = {2730-664X}, abstract = {Long COVID is prolonged illness resulting from SARS-CoV-2 infection. Its serious implications for individuals and society have been missing from public communication and pandemic policy. Here, I draw on my lived experience, research, and advocacy work with Long COVID and reflect on the lessons learnt.}, } @article {pmid35601952, year = {2022}, author = {Cobilinschi, C and Melente, OM and Bologa, C and Cotae, AM and Constantinescu, L and Bacruban, S and Grinţescu, IM}, title = {Cardiac tamponade - an unexpected "long COVID-19" complication.}, journal = {Germs}, volume = {12}, number = {1}, pages = {112-117}, pmid = {35601952}, issn = {2248-2997}, abstract = {INTRODUCTION: Year 2020 has been a cornerstone in medical research due to the COVID-19 pandemic outbreak. The process of understanding the condition brought to light certain organ involvement like pulmonary or kidney damage or endocrine disbalances, while connection to other types of organ impairment remain unclear. SARS-CoV-2 has previously been incriminated in cardiac involvement, ranging from mild symptoms to more severe occurrences such as myocarditis, arrythmias or heart failure, thus complicating the acute-phase management and worsening patients' prognosis. Despite being reported as an acute manifestation in critical COVID-19, cardiac tamponade seems to also occur as a "long- COVID19" complication. The latter is a distinct yet unclear entity associated with remanent fatigue or cough, but more severe sequelae like vasculitis or polyneuropathy can occsur.

CASE REPORT: We report the case of a 42-year-old patient admitted in the intensive care unit for severe respiratory and renal dysfunction one month after an initial mild episode of COVID-19. RT-PCR for SARS-CoV-2 on admission was negative. Initial imaging through CT and heart ultrasound revealed the presence of pericardial effusion but no signs of tamponade were initially obvious. Twelve hours later, the patient's state deteriorated with cardiocirculatory failure and signs of obstructive shock. Agents responsible for severe acute respiratory infection (SARI) such as influenza A and B, adenovirus, Bordetella pertussis, Mycoplasma pneumoniae, coxsackie virus, Chlamydia pneumoniae or parainfluenza viruses were ruled out. Surprisingly, RT-PCR testing for SARS-CoV-2 came back positive, although the initial test was negative. Repeated imaging confirmed massive circumferential pericardial effusion for which emergency pericardiocentesis was performed. Fluid was an exudate and histopathology reported chronic inflammation. RT-PCR testing for Mycoplasma tuberculosis in the pericardial tissue came back negative.

CONCLUSIONS: The case is to our knowledge among the first to report cardiac tamponade one month after mild COVID-19 infection. The aim of this case report is to raise awareness in the medical community on the possibility of severe complications targeting major organs in the long-COVID-19 phase.}, } @article {pmid35600811, year = {2023}, author = {Martin de Francisco, Á and Fernández Fresnedo, G}, title = {[Long COVID-19 renal disease: A present medical need for nephrology].}, journal = {Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia}, volume = {43}, number = {1}, pages = {1-5}, pmid = {35600811}, issn = {1989-2284}, } @article {pmid35599507, year = {2022}, author = {Braga, LW and Oliveira, SB and Moreira, AS and Pereira, ME and Carneiro, VS and Serio, AS and Freitas, LF and Isidro, HBL and Souza, LMN}, title = {Neuropsychological manifestations of long COVID in hospitalized and non-hospitalized Brazilian Patients.}, journal = {NeuroRehabilitation}, volume = {50}, number = {4}, pages = {391-400}, doi = {10.3233/NRE-228020}, pmid = {35599507}, issn = {1878-6448}, mesh = {Adult ; *Anxiety/etiology ; Brazil/epidemiology ; *COVID-19/complications ; *Cognition Disorders/etiology/psychology ; *Depression/etiology ; Humans ; Neuropsychological Tests ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: There has been a significant increase in number of patients seeking neuropsychological rehabilitation months after the acute phase of COVID-19 infection.

OBJECTIVE: Identify the cognitive and psychiatric disorders in patients with long COVID or Post-Acute Sequelae of COVID (PASC) and explore the association between disease severity during the acute phase and persistent neuropsychological manifestations.

METHODS: 614 adults were assessed an average of eight months post-infection. Participants were, on average, 47.6 y.o., who sought rehabilitation for neuropsychological problems. Patients were evaluated using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing tests (NEUPSILIN) for executive functions, and the Hospital Anxiety and Depression Scale (HADS).

RESULTS: The BNIS score was significantly below reference values in all subscales, especially affect and memory. Verbal Fluency and Clock Drawing subtest results were also lower. Patients with PASC tested high for anxiety/depression, but there was no statistically significant relationship between HADS and BNIS scores. Neuropsychological evaluations showed no differences in cognitive or psychiatric profiles between hospitalized and non-hospitalized patients.

CONCLUSIONS: Neuropsychological results suggest executive function problems and high incidence of anxiety/depression, irrespective of acute-phase severity, underscoring a need for neurorehabilitation programs while providing data for public policy initiatives.}, } @article {pmid35598567, year = {2022}, author = {Attia, MH}, title = {A cautionary note on altered pace of aging in the COVID-19 era.}, journal = {Forensic science international. Genetics}, volume = {59}, number = {}, pages = {102724}, pmid = {35598567}, issn = {1878-0326}, mesh = {Adult ; Aging/genetics ; Biomarkers ; *COVID-19/complications ; DNA/genetics ; Humans ; Reproducibility of Results ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is highly age-dependent due to hi-jacking the molecular control of the immune cells by the severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) leading to aberrant DNA methylation (DNAm) pattern of blood in comparison to normal individuals. These epigenetic modifications have been linked to perturbations to the epigenetic clock, development of long COVID-19 syndrome, and all-cause mortality risk. I reviewed the effects of COVID-19 on different molecular age markers such as the DNAm, telomere length (TL), and signal joint T-cell receptor excision circle (sjTREC). Integrating the accumulated clinical research data, COVID-19 and novel medical management may alter the pace of aging in adult individuals (<60 years). As such, COVID-19 might be a confounder in epigenetic age estimation similar to life style diversities, pathogens and pathologies which may influence the interpretation of DNAm data. Similarly, the SARS-CoV-2 affects T-lymphocyte function with possible influence on sjTREC levels. In contrast, TL measurements performed years before the SARS-CoV-2 pandemic proved that short TL predisposes to severe COVID- 19 independently from chronological age. However, the persistence of COVID-19 epigenetic scars and the durability of the immune response after vaccination and their effect on the ongoing pace of aging are still unknown. In the light of these data, the heterogeneous nature of the samples in these studies mandates a systematic evaluation of the currrent methods. SARS-CoV-2 may modify the reliability of the age estimation models in real casework because blood is the most common biological sample encountered in forensic contexts.}, } @article {pmid35598178, year = {2022}, author = {L'Huillier, AG and Pagano, S and Baggio, S and Meyer, B and Andrey, DO and Nehme, M and Guessous, I and Eberhardt, CS and Huttner, A and Posfay-Barbe, KM and Yerly, S and Siegrist, CA and Kaiser, L and Vuilleumier, N}, title = {Autoantibodies against apolipoprotein A-1 after COVID-19 predict symptoms persistence.}, journal = {European journal of clinical investigation}, volume = {52}, number = {10}, pages = {e13818}, pmid = {35598178}, issn = {1365-2362}, support = {657//De Reuter Foundation/ ; //Fondation Ancrage/ ; //Fondation de Bienfaisance du Groupe Pictet/ ; //Fondation Prive des HUG/ ; //Geneva University Hospitals and Faculty of Medicine's Center for Vaccinology/ ; //Geneva University Hospitals and Faculty of Medicine's Centre for Emerging Viral Diseases./ ; //Geneva University Hospitals Project and Development Grant/ ; //Schmidheiny Foundation/ ; }, mesh = {Antibodies, Viral ; Antiviral Agents ; Apolipoprotein A-I ; Autoantibodies ; *COVID-19 ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence.

METHODS: All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-α and-γ production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro.

RESULTS: AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3[rd] month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-α production by HMDMs (p = 0.03), without affecting the IFN-γ response.

CONCLUSION: COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-α response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.}, } @article {pmid35598023, year = {2022}, author = {Bloise, S and Isoldi, S and Marcellino, A and De Luca, E and Dilillo, A and Mallardo, S and Martucci, V and Sanseviero, M and Del Giudice, E and Iorfida, D and Leone, R and Testa, A and Frasacco, B and Gizzone, P and Proietti Ciolli, C and Sinceri, A and Zuliani, F and Zanardi, E and Gambarotto, A and Lisa Grandinetti, A and Ventriglia, F and Lubrano, R}, title = {Clinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {79}, pmid = {35598023}, issn = {1824-7288}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Child ; Humans ; Pandemics ; Quarantine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: SARS-CoV-2 infection in the pediatric age group has a milder course than in adults, but in some cases even children may present with severe forms or develop long-term consequences. The aim of this study was to analyze the clinical features, long-term effects, lifestyle changes and psychological effects of SARS-CoV-2 infection in a pediatric sample of the Italian population.

METHODS: We conducted a telephone survey among 3075 children infected with SARS-CoV-2 in the Latina Local Health Authority. Outcomes included: clinical features of infection, long-term symptoms, lifestyle changes and emotional symptoms during the illness. The information obtained was automatically linked to a spreadsheet and analyzed.

RESULTS: One thousand four hundred thirteen children agreed to participate in the study; the mean age was 112.8 ± 21.9 months. Children were infected mainly inside familial clusters (59.6%; n = 842); 99% (n = 1399) of children were asymptomatic or exhibited mild symptoms. 20% (n = 259) of children experienced long-term symptoms; risk factors were: older age, higher body mass index and longer duration of infection. Throughout the period of infection, children spent most of the time on devices like tv-video, social media and mobile phone for non-educational activities. 58.8% (n = 620) of parents expressed a negative opinion about distance learning. Finally, we observed that 49,6% (n = 532) of children experienced psychological symptoms during quarantine period.

CONCLUSION: Despite a lower susceptibility to COVID-19 in children, it is important to keep the focus high in children, both because of the possible long symptoms after infection and the impact on a children's mental and physical health due to pandemic. We believe that the return to school or other extracurricular activities are important to correct some of the risk factors for the long COVID syndrome, as obesity, and to limit the cultural damage generated by distance learning and psychological effects related to restrictive measures.}, } @article {pmid35596571, year = {2022}, author = {Healey, Q and Sheikh, A and Daines, L and Vasileiou, E}, title = {Symptoms and signs of long COVID: A rapid review and meta-analysis.}, journal = {Journal of global health}, volume = {12}, number = {}, pages = {05014}, pmid = {35596571}, issn = {2047-2986}, support = {COV/LTE/20/15/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Cohort Studies ; Humans ; Longitudinal Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is defined as symptoms and signs related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are present at least four weeks following acute infection. These symptoms and signs are poorly characterised but may be associated with significant morbidity. We sought to synthesise the evidence on their incidence to guide future research, policy and practice.

METHODS: We searched Medline and Embase for longitudinal cohort studies from January 2020 to July 2021 that investigated adults with long COVID at least four weeks after acute infection. Risk of bias was assessed using the Joanna Briggs Institute checklist for cohort studies. Random-effects meta-analyses were performed with subgroup analysis by follow-up time (4-12 vs more than 12 weeks).

RESULTS: 19 studies were included, 13 of which included patients hospitalised with COVID-19. The total sample size was 10 643 and the follow-up time ranged from 30 to 340 days. Risk of bias was assessed as high in one study, moderate in two studies and low in the remaining 16 studies. The most common symptoms and signs seen at any time point in long COVID were fatigue (37%; 95% confidence interval (CI) = 23-55), dyspnoea (21%; 95% CI = 14-30), olfactory dysfunction (17%; 95% CI = 9-29), myalgia (12%; 95% CI = 5-25), cough (11%; 95% CI = 6-20) and gustatory dysfunction (10%; 95% CI = 7-17). High heterogeneity was seen for all meta-analyses and the presence of some funnel plot asymmetry may indicate reporting bias. No effect of follow-up time was found for any symptom or sign included in the subgroup analysis.

CONCLUSIONS: We have summarised evidence from longitudinal cohort studies on the most common symptoms and signs associated with long COVID. High heterogeneity seen in the meta-analysis means pooled incidence estimates should be interpreted with caution. This heterogeneity may be attributable to studies including patients from different health care settings and countries.}, } @article {pmid35594336, year = {2022}, author = {Castanares-Zapatero, D and Chalon, P and Kohn, L and Dauvrin, M and Detollenaere, J and Maertens de Noordhout, C and Primus-de Jong, C and Cleemput, I and Van den Heede, K}, title = {Pathophysiology and mechanism of long COVID: a comprehensive review.}, journal = {Annals of medicine}, volume = {54}, number = {1}, pages = {1473-1487}, pmid = {35594336}, issn = {1365-2060}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: After almost 2 years of fighting against SARS-CoV-2 pandemic, the number of patients enduring persistent symptoms long after acute infection is a matter of concern. This set of symptoms was referred to as "long COVID", and it was defined more recently as "Post COVID-19 condition" by the World health Organization (WHO). Although studies have revealed that long COVID can manifest whatever the severity of inaugural illness, the underlying pathophysiology is still enigmatic.

AIM: To conduct a comprehensive review to address the putative pathophysiology underlying the persisting symptoms of long COVID.

METHOD: We searched 11 bibliographic databases (Cochrane Library, JBI EBP Database, Medline, Embase, PsycInfo, CINHAL, Ovid Nursing Database, Journals@Ovid, SciLit, EuropePMC, and CoronaCentral). We selected studies that put forward hypotheses on the pathophysiology, as well as those that encompassed long COVID patients in their research investigation.

RESULTS: A total of 98 articles were included in the systematic review, 54 of which exclusively addressed hypotheses on pathophysiology, while 44 involved COVID patients. Studies that included patients displayed heterogeneity with respect to the severity of initial illness, timing of analysis, or presence of a control group. Although long COVID likely results from long-term organ damage due to acute-phase infection, specific mechanisms following the initial illness could contribute to the later symptoms possibly affecting many organs. As such, autonomic nervous system damage could account for many symptoms without clear evidence of organ damage. Immune dysregulation, auto-immunity, endothelial dysfunction, occult viral persistence, as well as coagulation activation are the main underlying pathophysiological mechanisms so far.

CONCLUSION: Evidence on why persistent symptoms occur is still limited, and available studies are heterogeneous. Apart from long-term organ damage, many hints suggest that specific mechanisms following acute illness could be involved in long COVID symptoms. KEY MESSAGESLong-COVID is a multisystem disease that develops regardless of the initial disease severity. Its clinical spectrum comprises a wide range of symptoms.The mechanisms underlying its pathophysiology are still unclear. Although organ damage from the acute infection phase likely accounts for symptoms, specific long-lasting inflammatory mechanisms have been proposed, as well.Existing studies involving Long-COVID patients are highly heterogeneous, as they include patients with various COVID-19 severity levels and different time frame analysis, as well.}, } @article {pmid35590317, year = {2022}, author = {Rivera, J and Rodríguez, T and Pallarés, M and Castrejón, I and González, T and Vallejo-Slocker, L and Molina-Collada, J and Montero, F and Arias, A and Vallejo, MA and Alvaro-Gracia, JM and Collado, A}, title = {Prevalence of post-COVID-19 in patients with fibromyalgia: a comparative study with other inflammatory and autoimmune rheumatic diseases.}, journal = {BMC musculoskeletal disorders}, volume = {23}, number = {1}, pages = {471}, pmid = {35590317}, issn = {1471-2474}, mesh = {*Autoimmune Diseases ; *COVID-19/epidemiology ; COVID-19 Testing ; Fatigue/diagnosis/epidemiology ; *Fibromyalgia/diagnosis/epidemiology/psychology ; Humans ; Prevalence ; Retrospective Studies ; *Rheumatic Diseases/diagnosis/epidemiology ; Severity of Illness Index ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients.

METHODS: Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group.

RESULTS: RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p <  0.0001). Only loss of smell was more frequent in the FM group (p = 0.005). The FM group with PC (n = 29) showed more severity of the Combined Index of Severity in Fibromyalgia (ICAF) total score and physical factor after COVID-19, while emotional, coping factors and the ACR criteria did not change.

CONCLUSIONS: The prevalence of PC in FM patients is similar to RD patients. In FM patients, the presence of PC does not appear to impact the severity of FM.}, } @article {pmid35590069, year = {2022}, author = {Baker, N and Ledford, H}, title = {Coronapod: 'viral ghosts' support idea that SARS-CoV-2 reservoirs could be behind long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-01331-9}, pmid = {35590069}, issn = {1476-4687}, } @article {pmid35589549, year = {2022}, author = {Pfaff, ER and Girvin, AT and Bennett, TD and Bhatia, A and Brooks, IM and Deer, RR and Dekermanjian, JP and Jolley, SE and Kahn, MG and Kostka, K and McMurry, JA and Moffitt, R and Walden, A and Chute, CG and Haendel, MA and , }, title = {Identifying who has long COVID in the USA: a machine learning approach using N3C data.}, journal = {The Lancet. Digital health}, volume = {4}, number = {7}, pages = {e532-e541}, pmid = {35589549}, issn = {2589-7500}, support = {OT2 HL161847/HL/NHLBI NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *COVID-19/complications/diagnosis/epidemiology ; COVID-19 Testing ; Humans ; Machine Learning ; Pandemics ; SARS-CoV-2 ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, known as long COVID, have severely affected recovery from the COVID-19 pandemic for patients and society alike. Long COVID is characterised by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous definition. Studies of electronic health records are a crucial element of the US National Institutes of Health's RECOVER Initiative, which is addressing the urgent need to understand long COVID, identify treatments, and accurately identify who has it-the latter is the aim of this study.

METHODS: Using the National COVID Cohort Collaborative's (N3C) electronic health record repository, we developed XGBoost machine learning models to identify potential patients with long COVID. We defined our base population (n=1 793 604) as any non-deceased adult patient (age ≥18 years) with either an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) from an inpatient or emergency visit, or a positive SARS-CoV-2 PCR or antigen test, and for whom at least 90 days have passed since COVID-19 index date. We examined demographics, health-care utilisation, diagnoses, and medications for 97 995 adults with COVID-19. We used data on these features and 597 patients from a long COVID clinic to train three machine learning models to identify potential long COVID among all patients with COVID-19, patients hospitalised with COVID-19, and patients who had COVID-19 but were not hospitalised. Feature importance was determined via Shapley values. We further validated the models on data from a fourth site.

FINDINGS: Our models identified, with high accuracy, patients who potentially have long COVID, achieving areas under the receiver operator characteristic curve of 0·92 (all patients), 0·90 (hospitalised), and 0·85 (non-hospitalised). Important features, as defined by Shapley values, include rate of health-care utilisation, patient age, dyspnoea, and other diagnosis and medication information available within the electronic health record.

INTERPRETATION: Patients identified by our models as potentially having long COVID can be interpreted as patients warranting care at a specialty clinic for long COVID, which is an essential proxy for long COVID diagnosis as its definition continues to evolve. We also achieve the urgent goal of identifying potential long COVID in patients for clinical trials. As more data sources are identified, our models can be retrained and tuned based on the needs of individual studies.

FUNDING: US National Institutes of Health and National Center for Advancing Translational Sciences through the RECOVER Initiative.}, } @article {pmid35586759, year = {2022}, author = {Matsunaga, A and Tsuzuki, S and Morioka, S and Ohmagari, N and Ishizaka, Y}, title = {Long COVID: current status in Japan and knowledge about its molecular background.}, journal = {Global health & medicine}, volume = {4}, number = {2}, pages = {83-93}, pmid = {35586759}, issn = {2434-9194}, abstract = {Even after recovering from coronavirus disease 2019 (COVID-19), patients can experience prolonged complaints, referred to as "long COVID". Similar to reports in Caucasians, a follow-up study in Japan revealed that fatigue, dyspnea, cough, anosmia/dysgeusia, and dyssomnia are common symptoms. Although the precise mode of long COVID remains elusive, multiple etiologies such as direct organ damage by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), autoimmunity, prolonged inflammatory reactions, and psychiatric impairment seem to be involved. Notably, SARS-CoV-2 is neurotropic, and viral RNA and proteins are continuously detectable in multiple organs, including the brain. Viral proteins exert a number of different toxic effects on cells, suggesting that persistent infection is a key element for understanding long COVID. Here, we first reviewed the current status of long COVID in Japan, and then summarized literature that help us understand the molecular background of the symptoms. Finally, we discuss the feasibility of vaccination as a treatment for patients with long COVID.}, } @article {pmid35584895, year = {2022}, author = {Howell, J}, title = {COVID-19 narratives and layered temporality.}, journal = {Medical humanities}, volume = {48}, number = {2}, pages = {211-220}, doi = {10.1136/medhum-2021-012258}, pmid = {35584895}, issn = {1473-4265}, mesh = {*COVID-19/complications ; Humanities ; Humans ; Narration ; Post-Acute COVID-19 Syndrome ; }, abstract = {The essay outlines the ways in which narrative approaches to COVID-19 can draw on imaginative literature and critical oral history to resist the 'closure' often offered by cultural representations of epidemics. To support this goal, it analyses science and speculative fiction by Alejandro Morales and Tananarive Due in terms of how these works create alternative temporalities, which undermine colonial and racist medical discourse. The essay then examines a new archive of emerging autobiographical illness narratives, namely online Facebook posts and oral history samples by 'long COVID' survivors, for their alternate temporalities of illness.}, } @article {pmid35584848, year = {2022}, author = {Sivan, M and Greenhalgh, T and Milne, R and Delaney, B}, title = {Are vaccines a potential treatment for long covid?.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {o988}, doi = {10.1136/bmj.o988}, pmid = {35584848}, issn = {1756-1833}, mesh = {*COVID-19/complications/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; *Vaccines ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35584816, year = {2022}, author = {Ayoubkhani, D and Bermingham, C and Pouwels, KB and Glickman, M and Nafilyan, V and Zaccardi, F and Khunti, K and Alwan, NA and Walker, AS}, title = {Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {e069676}, pmid = {35584816}, issn = {1756-1833}, mesh = {Adult ; *COVID-19/complications/epidemiology/prevention & control ; COVID-19 Vaccines ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination.

DESIGN: Observational cohort study.

SETTING: Community dwelling population, UK.

PARTICIPANTS: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection.

MAIN OUTCOME MEASURE: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021.

RESULTS: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval -18.6% to -6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval -0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval -14.1% to -3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (-1.2% to -0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination.

CONCLUSIONS: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.}, } @article {pmid35580970, year = {2022}, author = {Sivan, M and Greenhalgh, T and Darbyshire, JL and Mir, G and O'Connor, RJ and Dawes, H and Greenwood, D and O'Connor, D and Horton, M and Petrou, S and de Lusignan, S and Curcin, V and Mayer, E and Casson, A and Milne, R and Rayner, C and Smith, N and Parkin, A and Preston, N and Delaney, B and , }, title = {LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION): protocol for a mixed-methods study in the UK.}, journal = {BMJ open}, volume = {12}, number = {5}, pages = {e063505}, pmid = {35580970}, issn = {2044-6055}, support = {G0501681/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications/therapy ; Humans ; Locomotion ; State Medicine ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID, a new condition whose origins and natural history are not yet fully established, currently affects 1.5 million people in the UK. Most do not have access to specialist long COVID services. We seek to optimise long COVID care both within and outside specialist clinics, including improving access, reducing inequalities, helping self-management and providing guidance and decision support for primary care. We aim to establish a 'gold standard' of care by systematically analysing current practices, iteratively improving pathways and systems of care.

METHODS AND ANALYSIS: This mixed-methods, multisite study is informed by the principles of applied health services research, quality improvement, co-design, outcome measurement and learning health systems. It was developed in close partnership with patients (whose stated priorities are prompt clinical assessment; evidence-based advice and treatment and help with returning to work and other roles) and with front-line clinicians. Workstreams and tasks to optimise assessment, treatment and monitoring are based in three contrasting settings: workstream 1 (qualitative research, up to 100 participants), specialist management in 10 long COVID clinics across the UK, via a quality improvement collaborative, experience-based co-design and targeted efforts to reduce inequalities of access, return to work and peer support; workstream 2 (quantitative research, up to 5000 participants), patient self-management at home, technology-supported monitoring and validation of condition-specific outcome measures and workstream 3 (quantitative research, up to 5000 participants), generalist management in primary care, harnessing electronic record data to study population phenotypes and develop evidence-based decision support, referral pathways and analysis of costs. Study governance includes an active patient advisory group.

ETHICS AND DISSEMINATION: LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS study is sponsored by the University of Leeds and approved by Yorkshire & The Humber-Bradford Leeds Research Ethics Committee (ref: 21/YH/0276). Participants will provide informed consent. Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers.

TRIAL REGISTRATION NUMBER: NCT05057260, ISRCTN15022307.}, } @article {pmid35579205, year = {2022}, author = {Nyström, S and Hammarström, P}, title = {Amyloidogenesis of SARS-CoV-2 Spike Protein.}, journal = {Journal of the American Chemical Society}, volume = {144}, number = {20}, pages = {8945-8950}, pmid = {35579205}, issn = {1520-5126}, mesh = {Amino Acid Sequence ; *Amyloid/chemistry ; Amyloidogenic Proteins/chemistry ; *COVID-19/complications ; Humans ; Leukocyte Elastase ; Peptides/chemistry ; Prospective Studies ; Protein Structure, Secondary ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus/chemistry ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 spike protein (S-protein). Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37 °C. Three 20-amino acid long synthetic spike peptides (sequence 192-211, 601-620, 1166-1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194-203, part of the most amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed sites of viral infection. Our data propose a molecular mechanism for potential amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The prospective of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis can be important in understanding the disease and long COVID-19.}, } @article {pmid35578802, year = {2022}, author = {Baslet, G and Aybek, S and Ducharme, S and Modirrousta, M and Nicholson, TR}, title = {Neuropsychiatry's Role in the Postacute Sequelae of COVID-19: Report From the American Neuropsychiatric Association Committee on Research.}, journal = {The Journal of neuropsychiatry and clinical neurosciences}, volume = {34}, number = {4}, pages = {341-350}, doi = {10.1176/appi.neuropsych.21080209}, pmid = {35578802}, issn = {1545-7222}, mesh = {Acute Disease ; *COVID-19/complications ; Disease Progression ; Humans ; *Neuropsychiatry ; United States ; }, abstract = {Postacute sequelae of COVID-19 can occur in patients who had only mild acute disease. A comprehensive neuropsychiatric approach reviews historical factors, provides objective assessment of symptoms, considers potential etiologies, and offers a therapeutic approach aimed at restoring premorbid functioning.}, } @article {pmid35578190, year = {2022}, author = {Lehmann, A and Gysan, M and Bernitzky, D and Bal, C and Prosch, H and Zehetmayer, S and Milos, RI and Vonbank, K and Pohl, W and Idzko, M and Gompelmann, D}, title = {Comparison of pulmonary function test, diffusion capacity, blood gas analysis and CT scan in patients with and without persistent respiratory symptoms following COVID-19.}, journal = {BMC pulmonary medicine}, volume = {22}, number = {1}, pages = {196}, pmid = {35578190}, issn = {1471-2466}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Gas Analysis ; *COVID-19/complications ; Humans ; Middle Aged ; Prospective Studies ; RNA, Viral ; Respiratory Function Tests ; SARS-CoV-2 ; Tomography, X-Ray Computed ; Young Adult ; }, abstract = {BACKGROUND: Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations.

METHODS: In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients.

RESULTS: In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042).

CONCLUSION: Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.}, } @article {pmid35578130, year = {2022}, author = {O'Leary, K}, title = {Lullabies for long COVID.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41591-022-00060-w}, pmid = {35578130}, issn = {1546-170X}, } @article {pmid35577377, year = {2022}, author = {McAlister, FA and Dong, Y and Chu, A and Wang, X and Youngson, E and Quinn, KL and Verma, A and Udell, JA and Yu, AYX and Razak, F and Ho, C and de Mestral, C and Ross, HJ and van Walraven, C and Lee, DS and , }, title = {The risk of death or unplanned readmission after discharge from a COVID-19 hospitalization in Alberta and Ontario.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {194}, number = {19}, pages = {E666-E673}, pmid = {35577377}, issn = {1488-2329}, mesh = {Adult ; Alberta/epidemiology ; *COVID-19/epidemiology/therapy ; Comorbidity ; Emergency Service, Hospital ; Hospitalization ; Humans ; Length of Stay ; Ontario/epidemiology ; Patient Discharge ; *Patient Readmission ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge.

METHODS: We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario.

RESULTS: Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission > 30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay > 30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73.

INTERPRETATION: Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.}, } @article {pmid35576613, year = {2022}, author = {Diep, PT and Chaudry, M and Dixon, A and Chaudry, F and Kasabri, V}, title = {Oxytocin, the panacea for long-COVID? a review.}, journal = {Hormone molecular biology and clinical investigation}, volume = {43}, number = {3}, pages = {363-371}, doi = {10.1515/hmbci-2021-0034}, pmid = {35576613}, issn = {1868-1891}, mesh = {*COVID-19/complications ; Humans ; *Neuropeptides ; Oxytocin/pharmacology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring the pro-health effects of the OXT neuropeptide.

METHODS: A review of published literature was surveyed using Google Scholar and PubMed.

RESULTS: Numerous experimental data can be shown to correlate with OXT and long-COVID symptoms and conditions, thus providing strong circumstantial evidence to support our hypothesis. It is postulated that the reduction in plasma OXT due to acute and post-viral damage to the hypothalamus and oxytocinergic neurones contributes to the variable multi-system, remitting and relapsing nature of long-COVID. The intranasal route of OXT application was determined to be most appropriate and clinically relevant for the restoration of oxytocinergic function post COVID-19 infection.

CONCLUSIONS: We believe it is imperative to further investigate whether OXT alleviates the prolonged suffering of patients with long-COVID. Succinctly, OXT may be the much-needed post-pandemic panacea.}, } @article {pmid35576015, year = {2022}, author = {Schilling, C and Meyer-Lindenberg, A and Schweiger, JI}, title = {[Cognitive disorders and sleep disturbances in long COVID].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {779-787}, pmid = {35576015}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Cognition ; Humans ; SARS-CoV-2 ; Sleep ; *Sleep Wake Disorders/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: During the last 2 years of the coronavirus disease 2019 (COVID-19) pandemic, knowledge about the long-term effects of the disease, the so-called long COVID, has rapidly grown; however, many questions remain unanswered, especially regarding the causes of persistent symptoms and their prognosis. Cognitive disorders and sleep disturbances are among the most frequent complaints. Both are associated with severe suffering and significant impairment in everyday functioning.

OBJECTIVE: What is known about the occurrence of cognitive disorders and sleep disturbances in long COVID? What are the influencing factors and what is known about the course over time and possible underlying mechanisms? What treatment options are available?

MATERIAL AND METHOD: In a narrative review, the most important findings on cognitive disorders and sleep disturbances in long COVID are presented. An overview of cohort studies with data on the prevalence and influencing factors of both symptom complexes is given. Current knowledge and hypotheses on pathophysiological mechanisms are presented and an outlook on treatment approaches is given.

RESULTS: About one in five of those affected report cognitive impairment more than 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and about one third report sleep disturbances. The latter comprise symptoms of insomnia as well as hypersomnia. Cognitive impairment and sleep disturbances occur in patients with all levels of initial disease severity. There are indications of an improvement of cognitive deficits over time but further longitudinal studies are needed.

CONCLUSION: In addition to the prognosis, the underlying disease mechanisms are still insufficiently understood. Furthermore, there is a great need for research on the efficacy and specific effective factors of therapeutic interventions.}, } @article {pmid35575989, year = {2022}, author = {Ocsovszky, Z and Otohal, J and Berényi, B and Juhász, V and Skoda, R and Bokor, L and Dohy, Z and Szabó, L and Nagy, G and Becker, D and Merkely, B and Vágó, H}, title = {The associations of long-COVID symptoms, clinical characteristics and affective psychological constructs in a non-hospitalized cohort.}, journal = {Physiology international}, volume = {}, number = {}, pages = {}, doi = {10.1556/2060.2022.00030}, pmid = {35575989}, issn = {2498-602X}, abstract = {OBJECTIVE: The effects of COVID-19, especially long-COVID, on the psychological health is incompletely understood. We aimed to evaluate the mid-term associations of the long-COVID symptoms and affective factors in a cohort of non-hospitalized patients.

METHOD: A total of 166 patients were enrolled in this study, including 119 sedentary/non-athlete and 47 athlete subjects at the Post-COVID Outpatient Clinic of Semmelweis University. Clinical data regarding acute and long-term symptoms were obtained and detailed laboratory testing was carried out. Demographic data and psychological tests were collected.

RESULTS: We found a positive association between the level of depressive symptoms and anxiety and long-COVID symptom count, while life satisfaction and social support correlated negatively with the long-COVID symptom count. Higher haemoglobin levels and lower LDL-cholesterol were also shown to be moderating factors. A regression model showed that symptoms during acute infection, depression, age, and life satisfaction are predictors of the long-COVID symptom count. The presence of pre-existing affective or anxiety problems was also associated with higher reported long-COVID symptom count. Furthermore, we found significant association between pre-existing mental health problems and the investigated psychological constructs.

CONCLUSION: It appears that long COVID-19 is associated with acute symptoms and mental factors. Depression and anxiety have been shown to have a negative effect on symptom perception, and also contribute to a higher number of symptoms in a non-hospitalized sample. Our study suggests bi-directional interconnection between clinical and psychological factors.}, } @article {pmid35573390, year = {2022}, author = {Weldetsadik, AY and Abayneh, M and Abraha, M and Sirgu, S and Bekele, D}, title = {Clinical Characteristics and Outcome of Pediatric COVID-19 Patients in Ethiopia During the Early COVID-19 Pandemic: A Prospective Cohort Study.}, journal = {Pediatric health, medicine and therapeutics}, volume = {13}, number = {}, pages = {165-174}, pmid = {35573390}, issn = {1179-9927}, abstract = {INTRODUCTION: Most previous pediatric COVID-19 studies reported milder disease in children. However, there are limited pediatric data from low-income settings. We aimed to assess the characteristics and outcomes of pediatric COVID-19 in Ethiopia.

SETTING: St. Paul's COVID-19 treatment center; a tertiary COVID-19 center. Pediatric care was provided in a dedicated ward but with a common ICU.

METHODS: St. Paul's Hospital COVID-19 cohort (SPC-19) included inpatient COVID-19 RT-PCR confirmed cases from August 2020 to January 2021. Data were extracted from case report forms attached to patient charts and completed by the clinicians. Data were uploaded into the Redcap database and exported to SPSS 20 for analysis. Binary logistic regression and chi-square test were used in the analysis.

RESULTS: Seventy-nine patients 0-19 years were included from the SPC-19 cohort over 6 months. Pediatric admissions accounted for 11% of cases in the cohort. The mean age (SD) was 6.9 (±6.36) years and 40 (50.6%) were female. The disease was asymptomatic or mild in 57 (72.2%), moderate in 15 (19%), and severe or critical in 7 (8.8%). The commonest presentations in symptomatic children were prostration (26.6%) followed by vomiting (12.7%), fever and cough (11.4% each), and dyspnea (10%). About 53 (67%) children had multimorbidity, and 14 (17.7%) children died. All deaths were in children with comorbidities with tuberculosis and malignancy being associated with 43% of deaths. Nearly 5% of children reported long-COVID symptoms highlighting the need for prolonged follow-up in those children.

CONCLUSION: Despite lower admissions and severity, high mortality and morbidity was documented in our pediatric cohort. The presence of comorbidity and inadequate care organization likely contributed to high mortality. COVID-19 centers of low-income settings should emphasize optimizing the care of children with COVID-19 and multimorbidity, and vaccination should be considered in those children to prevent high morbidity and mortality.}, } @article {pmid35572152, year = {2022}, author = {Rivas-Vazquez, RA and Rey, G and Quintana, A and Rivas-Vazquez, AA}, title = {Assessment and Management of Long COVID.}, journal = {Journal of health service psychology}, volume = {48}, number = {1}, pages = {21-30}, pmid = {35572152}, issn = {2662-2653}, abstract = {Almost two years into the pandemic, the scientific and healthcare communities continue to learn a great deal regarding COVID-19, the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Broad variability during acute COVID-19 infection is seen, ranging from asymptomatic presentation to death. The vast majority of individuals who develop COVID-19 return to their pre-COVID-19 baseline within several weeks. However, a portion of patients will develop a post-COVID-19 syndrome of persistent cognitive, somatic, and behavioral symptoms. This syndrome, designated as post-acute sequelae of SARS-CoV-2 infection, is more commonly known as long COVID. The objectives of this paper are to inform psychologists regarding our current understanding of the underlying pathophysiology of COVID-19, review criteria for range of severity during acute illness, present clinical manifestations of long haul phenomena, and discuss the emerging literature base of evidence-based treatment and management approaches.}, } @article {pmid35571554, year = {2022}, author = {Chang, YS}, title = {Coronavirus disease 2019 (COVID-19) and Long COVID.}, journal = {Asia Pacific allergy}, volume = {12}, number = {2}, pages = {e22}, pmid = {35571554}, issn = {2233-8276}, } @article {pmid35571551, year = {2022}, author = {Kang, YR and Oh, JY and Lee, JH and Small, PM and Chung, KF and Song, WJ}, title = {Long-COVID severe refractory cough: discussion of a case with 6-week longitudinal cough characterization.}, journal = {Asia Pacific allergy}, volume = {12}, number = {2}, pages = {e19}, pmid = {35571551}, issn = {2233-8276}, abstract = {Long coronavirus disease (COVID) refers to an array of variable and fluctuating symptoms experienced after acute illness, with signs and symptoms that persist for 8-12 weeks and are not otherwise explicable. Cough is the most common symptom of acute COVID-19, but cough may persist in some individuals for weeks or months after recovery from acute phase. Long-COVID cough patients may get stigmatised because of the public fear of contagion and reinfection. However, clinical characteristics and longitudinal course of long-COVID cough have not been reported in detail, and evidence-based treatment is also lacking. In this paper, we describe a case of long-COVID severe refractory cough with features of laryngeal hypersensitivity and dysfunction. We characterized cough using patient-reported outcomes and engaged in continuous cough frequency monitoring. Through the case study, we discuss potential mechanisms, managements, and clinical implications of long-COVID refractory cough problems.}, } @article {pmid35571200, year = {2022}, author = {Marques, KC and Silva, CC and Trindade, SDS and Santos, MCS and Rocha, RSB and Vasconcelos, PFDC and Quaresma, JAS and Falcão, LFM}, title = {Reduction of Cardiac Autonomic Modulation and Increased Sympathetic Activity by Heart Rate Variability in Patients With Long COVID.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {862001}, pmid = {35571200}, issn = {2297-055X}, abstract = {Although several clinical manifestations of persistent long coronavirus disease (COVID-19) have been documented, their effects on the cardiovascular and autonomic nervous system over the long term remain unclear. Thus, we examined the presence of alterations in cardiac autonomic functioning in individuals with long-term manifestations. The study was conducted from October 2020 to May 2021, and an autonomic assessment was performed to collect heart rate data for the heart rate variability (HRV) analysis. The study participants were divided into the long COVID clinical group, the intragroup, which included patients who were hospitalized, and those who were not hospitalized and were symptomatic for different periods (≤3, >3, ≤6, and >6 months), with and without dyspnoea. The control group, the intergroup, comprised of COVID-free individuals. Our results demonstrated that the long COVID clinical group showed reduced HRV compared with the COVID-19-uninfected control group. Patients aged 23-59 years developed COVID symptoms within 30 days after infection, whose diagnosis was confirmed by serologic or reverse-transcription polymerase chain reaction (swab) tests, were included in the study. A total of 155 patients with long COVID [95 women (61.29%), mean age 43.88 ± 10.88 years and 60 men (38.71%), mean age 43.93 ± 10.11 years] and 94 controls [61 women (64.89%), mean age 40.83 ± 6.31 and 33 men (35.11%), mean age 40.69 ± 6.35 years] were included. The intragroup and intergroup comparisons revealed a reduction in global HRV, increased sympathetic modulation influence, and a decrease in parasympathetic modulation in long COVID. The intragroup showed normal sympathovagal balance, while the intergroup showed reduced sympathovagal balance. Our findings indicate that long COVID leads to sympathetic excitation influence and parasympathetic reduction. The excitation can increase the heart rate and blood pressure and predispose to cardiovascular complications. Short-term HRV analysis showed good reproducibility to verify the cardiac autonomic involvement.}, } @article {pmid35571085, year = {2022}, author = {Vollbracht, C and Kraft, K}, title = {Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {899198}, pmid = {35571085}, issn = {1663-9812}, abstract = {Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.}, } @article {pmid35570247, year = {2022}, author = {Miglis, MG and Seliger, J and Shaik, R and Gibbons, CH}, title = {A case series of cutaneous phosphorylated α-synuclein in Long-COVID POTS.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {32}, number = {3}, pages = {209-212}, pmid = {35570247}, issn = {1619-1560}, mesh = {*COVID-19/complications ; Humans ; *Lewy Body Disease ; *Parkinson Disease ; alpha-Synuclein ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35570238, year = {2022}, author = {Hennigs, JK and Huwe, M and Hennigs, A and Oqueka, T and Simon, M and Harbaum, L and Körbelin, J and Schmiedel, S and Schulze Zur Wiesch, J and Addo, MM and Kluge, S and Klose, H}, title = {Respiratory muscle dysfunction in long-COVID patients.}, journal = {Infection}, volume = {50}, number = {5}, pages = {1391-1397}, pmid = {35570238}, issn = {1439-0973}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Humans ; Pilot Projects ; Respiratory Muscles/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Symptoms often persistent for more than 4 weeks after COVID-19-now commonly referred to as 'Long COVID'. Independent of initial disease severity or pathological pulmonary functions tests, fatigue, exertional intolerance and dyspnea are among the most common COVID-19 sequelae. We hypothesized that respiratory muscle dysfunction might be prevalent in persistently symptomatic patients after COVID-19 with self-reported exercise intolerance.

METHODS: In a small cross-sectional pilot study (n = 67) of mild-to-moderate (nonhospitalized) and moderate-to-critical convalescent (formerly hospitalized) patients presenting to our outpatient clinic approx. 5 months after acute infection, we measured neuroventilatory activity P0.1, inspiratory muscle strength (PImax) and total respiratory muscle strain (P0.1/PImax) in addition to standard pulmonary functions tests, capillary blood gas analysis, 6 min walking tests and functional questionnaires.

RESULTS: Pathological P0.1/PImax was found in 88% of symptomatic patients. Mean PImax was reduced in hospitalized patients, but reduced PImax was also found in 65% of nonhospitalized patients. Mean P0.1 was pathologically increased in both groups. Increased P0.1 was associated with exercise-induced deoxygenation, impaired exercise tolerance, decreased activity and productivity and worse Post-COVID-19 functional status scale. Pathological changes in P0.1, PImax or P0.1/PImax were not associated with pre-existing conditions.

CONCLUSIONS: Our findings point towards respiratory muscle dysfunction as a novel aspect of COVID-19 sequelae. Thus, we strongly advocate for systematic respiratory muscle testing during the diagnostic workup of persistently symptomatic, convalescent COVID-19 patients.}, } @article {pmid35568518, year = {2022}, author = {Reis, J and Buguet, A and Román, GC and Spencer, PS}, title = {The COVID-19 pandemic, an environmental neurology perspective.}, journal = {Revue neurologique}, volume = {178}, number = {6}, pages = {499-511}, pmid = {35568518}, issn = {0035-3787}, mesh = {*COVID-19/complications/epidemiology ; Humans ; *Neurology ; Pandemics/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurologists have a particular interest in SARS-CoV-2 because the nervous system is a major participant in COVID-19, both in its acute phase and in its persistent post-COVID phase. The global spread of SARS-CoV-2 infection has revealed most of the challenges and risk factors that humanity will face in the future. We review from an environmental neurology perspective some characteristics that have underpinned the pandemic. We consider the agent, SARS-CoV-2, the spread of SARS-CoV-2 as influenced by environmental factors, its impact on the brain and some containment measures on brain health. Several questions remain, including the differential clinical impact of variants, the impact of SARS-CoV-2 on sleep and wakefulness, and the neurological components of Long-COVID syndrome. We touch on the role of national leaders and public health policies that have underpinned management of the COVID-19 pandemic. Increased awareness, anticipation and preparedness are needed to address comparable future challenges.}, } @article {pmid35568052, year = {2022}, author = {Huang, L and Li, X and Gu, X and Zhang, H and Ren, L and Guo, L and Liu, M and Wang, Y and Cui, D and Wang, Y and Zhang, X and Shang, L and Zhong, J and Wang, X and Wang, J and Cao, B}, title = {Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {9}, pages = {863-876}, pmid = {35568052}, issn = {2213-2619}, mesh = {Child, Preschool ; Female ; Humans ; Male ; *COVID-19/complications/epidemiology/therapy ; Dyspnea ; Hospitalization ; Longitudinal Studies ; Outcome Assessment, Health Care ; Pandemics ; Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {BACKGROUND: With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status.

METHODS: We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls.

FINDINGS: 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls.

INTERPRETATION: Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.}, } @article {pmid35567575, year = {2022}, author = {Sorensen, JM and Crooks, VA and Freeman, S and Carroll, S and Davison, KM and MacPhee, M and Berndt, A and Walls, J and Mithani, A}, title = {A call to action to enhance understanding of long COVID in long-term care home residents.}, journal = {Journal of the American Geriatrics Society}, volume = {70}, number = {7}, pages = {1943-1945}, pmid = {35567575}, issn = {1532-5415}, support = {FAFM-2021-0094-EN_Mithani//COVID-19 Pandemic Response and Impact Grant (Co-RIG) Program of the Foundation for Advancing Family Medicine and the Canadian Medical Association Foundation/ ; }, mesh = {*COVID-19/complications ; Humans ; *Long-Term Care ; Nursing Homes ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35566536, year = {2022}, author = {Sperling, S and Fløe, A and Leth, S and Hyldgaard, C and Gissel, T and Topcu, A and Kristensen, L and Sønderskov, LD and Schmid, JM and Jensen-Fangel, S and Bendstrup, E}, title = {Fatigue Is a Major Symptom at COVID-19 Hospitalization Follow-Up.}, journal = {Journal of clinical medicine}, volume = {11}, number = {9}, pages = {}, pmid = {35566536}, issn = {2077-0383}, support = {NNF21OC0066984//Novo Nordisk Foundation/ ; }, abstract = {Persistent symptoms after hospitalization with COVID-19 are common, but the frequency and severity of these symptoms are insufficiently understood. We aimed to describe symptoms and pulmonary function after hospitalization with COVID-19. Patients hospitalized with COVID-19 in Central Denmark Region were invited for follow-up 3 months after discharge. Clinical characteristics, patient reported outcomes (Fatigue Assessment Scale (FAS), anxiety and depression (HADS)), symptoms, pulmonary function test and 6-min walk test were collected. We included 218 patients (mean age 59.9 (95% CI: 58.2, 61.7), 59% males). Fatigue, dyspnea and impaired concentration were the most prevalent symptoms at follow-up. Using FAS, 47% reported mild-to-moderate fatigue and 18% severe fatigue. Mean HADS was 7.9 (95% CI: 6.9, 8.9). FAS was correlated to HADS (β = 0.52 (95% CI: 0.44, 0.59, p < 0.001)). Mean DLCO was 80.4% (95% CI: 77.8, 83.0) and 45% had DLCO ˂ 80%. Mean DLCO was significantly reduced in patients treated in the ICU (70.46% (95% CI 65.13, 75.79)). The highest FAS and HADS were seen in patients with the shortest period of hospitalization (2.1 days (95% CI: 1.4, 2.7)) with no need for oxygen. In conclusion, fatigue is a common symptom after hospitalization for COVID-19 and ICU treatment is associated to decreased diffusion capacity.}, } @article {pmid35566502, year = {2022}, author = {Romero-Ortuno, R and Jennings, G and Xue, F and Duggan, E and Gormley, J and Monaghan, A}, title = {Predictors of Submaximal Exercise Test Attainment in Adults Reporting Long COVID Symptoms.}, journal = {Journal of clinical medicine}, volume = {11}, number = {9}, pages = {}, pmid = {35566502}, issn = {2077-0383}, support = {/WT_/Wellcome Trust/United Kingdom ; 20/COV/8493 and 18/FRL/6188/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {Adults with long COVID often report intolerance to exercise. Cardiopulmonary exercise testing (CPET) has been used in many settings to measure exercise ability but has been conducted in a few long COVID cohorts. We conducted CPET in a sample of adults reporting long COVID symptoms using a submaximal cycle ergometer protocol. We studied pre-exercise predictors of achieving 85% of the age-predicted maximum heart rate (85%HRmax) using logistic regression. Eighty participants were included (mean age 46 years, range 25−78, 71% women). Forty participants (50%) did not reach 85%HRmax. On average, non-achievers reached 84% of their predicted 85%HRmax. No adverse events occurred. Participants who did not achieve 85%HRmax were older (p < 0.001), had more recent COVID-19 illness (p = 0.012) with higher frequency of hospitalization (p = 0.025), and had been more affected by dizziness (p = 0.041) and joint pain (p = 0.028). In the logistic regression model including age, body mass index, time since COVID-19, COVID-19-related hospitalization, dizziness, joint pain, pre-existing cardiopulmonary disease, and use of beta blockers, independent predictors of achieving 85%HRmax were younger age (p = 0.001) and longer time since COVID-19 (p = 0.008). Our cross-sectional findings suggest that exercise tolerance in adults with long COVID has potential to improve over time. Longitudinal research should assess the extent to which this may occur and its mechanisms. ClinicalTrials.gov identifier: NCT05027724 (TROPIC Study).}, } @article {pmid35566253, year = {2022}, author = {Khazaal, S and Harb, J and Rima, M and Annweiler, C and Wu, Y and Cao, Z and Abi Khattar, Z and Legros, C and Kovacic, H and Fajloun, Z and Sabatier, JM}, title = {The Pathophysiology of Long COVID throughout the Renin-Angiotensin System.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {9}, pages = {}, pmid = {35566253}, issn = {1420-3049}, mesh = {Angiotensin-Converting Enzyme 2 ; *COVID-19/complications ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System/physiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people's lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.}, } @article {pmid35564663, year = {2022}, author = {Romaszko-Wojtowicz, A and Maksymowicz, S and Jarynowski, A and Jaśkiewicz, Ł and Czekaj, Ł and Doboszyńska, A}, title = {Telemonitoring in Long-COVID Patients-Preliminary Findings.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564663}, issn = {1660-4601}, mesh = {*COVID-19/complications/diagnosis ; Humans ; Pandemics ; SARS-CoV-2 ; *Telemedicine/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has revealed the high usefulness of telemedicine. To date, no uniform recommendations or diagnostic protocols for long-COVID patients have been developed. This article presents the preliminary results of the examination of patients after SARS-CoV-2 infection who were provided with medical telemonitoring devices in order to oversee their pulmonological and cardiological health. Three cases have been analyzed. Each patient underwent a 10-day registration of basic vital signs, in three 15-min sessions daily: RR (respiratory rate), ECG (electrocardiogram), HR (pulse), SPO2 (saturation), body temperature and cough. Rule methods and machine learning were employed to automatically detect events. As a result, serious disorders of all the three patients were detected: cardiological and respiratory disorders that required extended diagnostics. Furthermore, average values of the selected parameters (RR, HR, SPO2) were calculated for every patient, including an indication of how often they exceeded the alarm thresholds. In conclusion, monitoring parameters in patients using telemedicine, especially in a time of limited access to the healthcare system, is a valuable clinical instrument. It enables medical professionals to recognize conditions which may endanger a patient's health or life. Telemedicine provides a reliable assessment of a patient's health status made over a distance, which can alleviate a patient's stress caused by long-COVID syndrome. Telemedicine allows identification of disorders and performing further diagnosis, which is possible owing to the implementation of advanced analysis. Telemedicine, however, requires flexibility and the engagement of a multidisciplinary team, who will respond to patients' problems on an ongoing basis.}, } @article {pmid35564579, year = {2022}, author = {Fugazzaro, S and Contri, A and Esseroukh, O and Kaleci, S and Croci, S and Massari, M and Facciolongo, NC and Besutti, G and Iori, M and Salvarani, C and Costi, S and , }, title = {Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564579}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Dyspnea ; Exercise Therapy/methods ; Female ; Humans ; Male ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2-69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had "low risk of bias", and three were in the "some concerns" category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.}, } @article {pmid35564488, year = {2022}, author = {Wright, J and Astill, SL and Sivan, M}, title = {The Relationship between Physical Activity and Long COVID: A Cross-Sectional Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {9}, pages = {}, pmid = {35564488}, issn = {1660-4601}, mesh = {Activities of Daily Living ; Adult ; *COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Exercise ; Female ; Humans ; Male ; Middle Aged ; Post-Acute COVID-19 Syndrome ; }, abstract = {The relationship between Long Covid (LC) symptoms and physical activity (PA) levels are unclear. In this cross-sectional study, we examined this association, and the advice that individuals with LC received on PA. Adults with LC were recruited via social media. The New Zealand physical activity questionnaire short form (NZPAQ-SF) was adapted to capture current and pre-COVID-19 PA levels and activities of daily living (ADLs). Participants reported how PA affected their symptoms, and what PA recommendations they had received from healthcare professionals and other resources; 477 participants completed the survey. Mean age (SD) was 45.69 (10.02) years, 89.1% female, 92.7% white, and median LC duration was 383.5 days (IQR: 168.25,427). Participants were less active than pre-COVID-19 (26.88 ± 74.85 vs. 361.68 ± 396.29 min per week, p < 0.001) and required more assistance with ADLs in a 7-day period compared to pre-COVID-19 (2.23 ± 2.83 vs. 0.11 ± 0.74 days requiring assistance, p < 0.001). No differences were found between the number of days of assistance required with ADLs, or the amount of PA, and the different durations of LC illness (p > 0.05). Participants reported the effect of PA on LC symptoms as: worsened (74.84%), improved (0.84%), mixed effect (20.96%), or no effect (28.72%). Participants received contradictory advice on whether to be physically active in LC. LC is associated with a reduction in PA and a loss of independence, with most participants reporting PA worsened LC symptoms. PA level reduction is independent of duration of LC. Research is needed to understand how to safely return to PA without worsening LC symptoms.}, } @article {pmid35562145, year = {2022}, author = {Lin, LC and Hollis, B and Hefti, MM}, title = {Neuropathology of COVID-19.}, journal = {Indian journal of pathology & microbiology}, volume = {65}, number = {Supplement}, pages = {S146-S152}, doi = {10.4103/ijpm.ijpm_1103_21}, pmid = {35562145}, issn = {0974-5130}, mesh = {Aged ; Brain/pathology ; *COVID-19 ; Humans ; *Neurodegenerative Diseases/pathology ; Pandemics ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has placed global health care systems under unprecedented strain but has, at the same time, provided a unique opportunity for pathologists to turn autopsy findings into directly actionable insights into patient care. The current data on the neuropathology of COVID-19 remains preliminary and is limited by the lack of suitable controls, but certain tentative conclusions can be drawn. SARS-CoV-2 can infect multiple cell types in the central nervous system and does so in a subset of patients, although the clinical significance of direct infections remains in the central nervous system (CNS) and the peripheral nervous system (PNS) infections remains unclear. The best-described neuropathological manifestations of COVID-19 in the brain are variable patterns of neuroinflammation and vascular injury, although again, it remains unclear to what degree these findings are specifically due to COVID-19. There is also intriguing preliminary data to suggest a complex relationship between COVID-19 and neurodegeneration, with certain alleles that increase AD risk also increasing the risk of severe COVID-19, and conversely, the possibility that COVID-19 may increase the risk of neurodegenerative disease. The neuropathology of so-called "long-COVID" and the potential effects of COVID-19, or critical illness in general, on neurodegenerative disease remains unclear. There is thus an urgent need for long-term cohort studies of COVID-19 survivors, including brain donation, particularly in elderly patients, with careful recruitment of controls with similar non-COVID inflammatory illnesses.}, } @article {pmid35561352, year = {2022}, author = {Meagher, T}, title = {Long COVID - One Year On.}, journal = {Journal of insurance medicine (New York, N.Y.)}, volume = {49}, number = {3}, pages = {183-188}, doi = {10.17849/insm-49-3-1-6.1}, pmid = {35561352}, issn = {0743-6661}, mesh = {Humans ; *COVID-19/epidemiology ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is now a recognized complication of acute COVID-19 infection. As the COVID-19 pandemic moves into its third year, the prevalence of Long COVID continues to increase. Many individuals report symptoms lasting longer than a year, and a subset of this group is unable to work. This article will provide an update on Long COVID, with a particular focus on distinguishing it from other clinical entities. It will review several proposed disease mechanisms and will attempt to anticipate the impact on disability insurance.}, } @article {pmid35557480, year = {2022}, author = {Ireson, J and Taylor, A and Richardson, E and Greenfield, B and Jones, G}, title = {Exploring invisibility and epistemic injustice in Long Covid-A citizen science qualitative analysis of patient stories from an online Covid community.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {25}, number = {4}, pages = {1753-1765}, pmid = {35557480}, issn = {1369-7625}, support = {202022/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Trust ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: In 2020, the long-lasting effects of the Covid-19 virus were not included in public messages of risks to public health. Long Covid emerged as a novel and enigmatic illness with a serious and life-changing impact. Long Covid is poorly explained by objective medical tests, leading to widespread disbelief and stigma associated with the condition. The aim of this organic research is to explore the physical and epistemic challenges of living with Long Covid.

METHODS: Unlike any previous pandemic in history, online Covid communities and 'citizen science' have played a leading role in advancing our understanding of Long Covid. As patient-led research of this grassroots Covid community, a team approach to thematic analysis was undertaken of 66 patient stories submitted online to covid19-recovery.org at the beginning of the Covid-19 pandemic between April and September 2020.

RESULTS: The overriding theme of the analysis highlights the complexities and challenges of living with Long Covid. Our distinct themes were identified: the life-changing impact of the condition, the importance of validation and how, for many, seeking alternatives was felt to be their only option.

CONCLUSIONS: Long Covid does not easily fit into the dominant evidence-based practice and the biomedical model of health, which rely on objective indicators of the disease process. Patient testimonies are vital to understanding and treating Long Covid, yet patients are frequently disbelieved, and their testimonies are not taken seriously leading to stigma and epistemic injustice, which introduces a lack of trust into the therapeutic relationship.

PATIENT CONTRIBUTION: The research was undertaken in partnership with our consumer representative(s) and all findings and subsequent recommendations have been coproduced.}, } @article {pmid35552722, year = {2022}, author = {Mezlini, A and Shapiro, A and Daza, EJ and Caddigan, E and Ramirez, E and Althoff, T and Foschini, L}, title = {Estimating the Burden of Influenza-like Illness on Daily Activity at the Population Scale Using Commercial Wearable Sensors.}, journal = {JAMA network open}, volume = {5}, number = {5}, pages = {e2211958}, pmid = {35552722}, issn = {2574-3805}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Cohort Studies ; Female ; Humans ; *Influenza, Human/diagnosis/epidemiology ; Male ; Pandemics ; *Virus Diseases/epidemiology ; *Wearable Electronic Devices ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: The severity of viral infections can vary widely, from asymptomatic cases to complications leading to hospitalizations and death. Milder cases, despite being more prevalent, often go undocumented, and their public health burden is not accurately estimated.

OBJECTIVE: To estimate the true burden of influenza-like illness (ILI) in the US population using a surrogate measure of daily steps lost as measured by commercial wearable sensors.

This cohort study modeled data from 15 122 US adults who reported ILI symptoms during the 2018-2019 influenza season (before the COVID-19 pandemic) and who had a sufficient density of wearable sensor data at symptom onset. Participants' minute-level step data as measured by commercial wearable sensors were collected from October 1, 2018, through June 30, 2019. Minute-level activity time series were transformed into day-level time series per user, indicating the total number of steps daily.

MAIN OUTCOMES AND MEASURES: The primary end point was the number of steps lost during the period of 4 days before symptom onset (the latent phase) through 11 days after symptom onset (the symptomatic phase). The association between covariates and steps lost during this interval was also examined.

RESULTS: Of the 15 122 participants in this study, 13 108 (86.7%) were women, and the median age was 32 years (IQR, 27-38 years). For their ILI event, 2836 of 15 080 participants (18.8%) sought medical attention, and only 61 (0.4%) were hospitalized. Over the course of an ILI lasting 10 days, the mean cumulative loss was 4437 steps (95% CI, 4143-4731 steps). After weighting, there was an estimated overall nationwide reduction in mobility equivalent to 255.2 billion steps (95% CI, 232.9-277.6 billion steps) lost because of ILI symptoms during the study period. This finding reflects significant changes in routines, mobility, and employment and is equivalent to 15% of the active US population becoming completely immobilized for 1 day. Moreover, 60.6% of this reduction in steps (154.6 billion steps [95% CI, 138.1-171.2 billion steps]) occurred among persons who sought no medical care. Age and educational level were positively associated with steps lost.

CONCLUSIONS AND RELEVANCE: These findings suggest that most of the burden of ILI in this study would have been invisible to health care and public health reporting systems. This approach has applications for public health, health care, and clinical research, from estimating costs of lost productivity at population scale, to measuring effectiveness of anti-ILI treatments, to monitoring recovery after acute viral syndromes such as during long COVID-19.}, } @article {pmid35552501, year = {2022}, author = {Richter, D and Schulze, H and James, JC and Siems, N and Trampe, N and Gold, R and Krogias, C and Faissner, S}, title = {Hypoechogenicity of brainstem raphe in long-COVID syndrome-less common but independently associated with depressive symptoms: a cross-sectional study.}, journal = {Journal of neurology}, volume = {269}, number = {9}, pages = {4604-4610}, pmid = {35552501}, issn = {1432-1459}, mesh = {Anxiety/diagnostic imaging ; Brain Stem/diagnostic imaging ; *COVID-19/complications/diagnostic imaging ; Cross-Sectional Studies ; *Depression/diagnostic imaging ; Humans ; Ultrasonography, Doppler, Transcranial ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Long coronavirus disease (Long-COVID) syndrome is a hitherto poorly understood phenomenon with a broad spectrum of symptoms, including depression and anxiety. Depressive symptoms have been associated with brainstem raphe (BR) alterations in transcranial sonography (TCS) that might reflect dysfunction of the serotonergic system. The primary aim was to investigate the connection of BR alterations with depressive and anxiety symptoms in patients with Long-COVID syndrome.

METHODS: In a cross-sectional study design, we included outpatients fulfilling the criteria of Long-COVID syndrome. All patients were examined by TCS in the axial plane with focus on BR signal alterations. The Hospital Anxiety and Depression Scale (HADS) was used to test for symptoms of anxiety and depression.

RESULTS: We included n = 70 patients with Long-COVID syndrome, of which 28.6% (n = 20) exhibited a reduced echogenicity of BR in the TCS examination. Patients with hypoechogenic BR had higher subscores for anxiety and depression compared to normoechogenic patients (HADS depression: median 8 versus 5.5, p = 0.006; HADS anxiety: median 9 versus 6.5, p = 0.006). After adjustment for reasonable confounders, only the odds ratio (OR) for relevant depressive symptoms was higher among Long-COVID patients with hypoechogenic raphe (adjusted OR 3.884, 95% CI 1.244-12.123).

DISCUSSION: Hypoechogenic BR alterations are independently associated with depressive symptoms in Long-COVID patients but are not highly frequent. Future studies should investigate whether the hypoechogenicity of the BR is a direct consequence or whether it reflects a priori a higher susceptibility to depressive symptoms after COVID-19, thus enabling to identify COVID-19 patients at higher risk of developing Long-COVID depressive symptoms.}, } @article {pmid35552466, year = {2022}, author = {Gerhard, A and Prüß, H and Franke, C}, title = {[Manifestations of the central nervous system after COVID-19].}, journal = {Der Nervenarzt}, volume = {93}, number = {8}, pages = {769-778}, pmid = {35552466}, issn = {1433-0407}, mesh = {*COVID-19/complications ; Central Nervous System ; Humans ; *Nervous System Diseases/etiology ; *Posterior Leukoencephalopathy Syndrome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Numerous diseases of the central nervous system (CNS), especially in the postacute phase after an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described. These include neuroimmunologically mediated diseases, such as encephalopathy, encephalitis, myelitis, acute disseminated encephalomyelitis (ADEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE) and neuromyelitis optica spectrum disorder (NMOSD) as well as others, such as posterior reversible encephalopathy syndrome (PRES), opsoclonus myoclonus ataxia (OMA) and cerebrovascular diseases. A parainfectious or postinfectious association is discussed but the pathophysiological mechanisms are so far unknown. Underlying mechanisms could be a virus-triggered overactivation of the immune system with hyperinflammation and cytokine storm but possibly also the development of specific autoantibodies against CNS tissue. Direct damage due to the invasion of SARS-CoV‑2 into the brain or spinal cord does not seem to play a relevant role. An exact clinical phenotyping and initiation of additional diagnostics are recommended, also to rule out other causes. To date no medicinal treatment options for CNS manifestations of long COVID exist; however, first results regarding inflammation and autoimmunity are promising and could lead to new treatment approaches.}, } @article {pmid35548336, year = {2022}, author = {Raghavan, S and Leo, MD}, title = {Histamine Potentiates SARS-CoV-2 Spike Protein Entry Into Endothelial Cells.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {872736}, pmid = {35548336}, issn = {1663-9812}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease (COVID-19) is one of the most serious global health crises in recent history. COVID-19 patient symptoms range from life-threatening to mild and asymptomatic, which presents unique problems in identifying, quarantining, and treating the affected individuals. The emergence of unusual symptoms among survivors, now referred to as "Long COVID", is concerning, especially since much about the condition and the treatment of it is still relatively unknown. Evidence so far also suggests that some of these symptoms can be attributed to vascular inflammation. Although famotidine, the commonly used histamine H2 receptor (H2R) blocker, was shown to have no antiviral activity, recent reports indicate that it could prevent adverse outcomes in COVID-19 patients. Histamine is a classic proinflammatory mediator, the levels of which increase along with other cytokines during COVID-19 infection. Histamine activates H2R signaling, while famotidine specifically blocks H2R activation. Investigating the effects of recombinant SARS-CoV-2 spike protein S1 Receptor-Binding Domain (Spike) on ACE2 expression in cultured human coronary artery endothelial cells, we found that the presence of histamine potentiated spike-mediated ACE2 internalization into endothelial cells. This effect was blocked by famotidine, protein kinase A inhibition, or by H2 receptor protein knockdown. Together, these results indicate that histamine and histamine receptor signaling is likely essential for spike protein to induce ACE2 internalization in endothelial cells and cause endothelial dysfunction and that this effect can be blocked by the H2R blocker, famotidine.}, } @article {pmid35547372, year = {2022}, author = {Degen, CV and Mikuteit, M and Niewolik, J and Schröder, D and Vahldiek, K and Mücke, U and Heinemann, S and Müller, F and Behrens, GMN and Klawonn, F and Dopfer-Jablonka, A and Steffens, S}, title = {Self-reported Tinnitus and Vertigo or Dizziness in a Cohort of Adult Long COVID Patients.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {884002}, pmid = {35547372}, issn = {1664-2295}, abstract = {Tinnitus, vertigo and dizziness are symptoms commonly reported among Long and Post COVID patients, however the severity of these symptoms has not been assessed in large trials. Therefore, in this study a large cohort of Long COVID patients was surveyed about the presence and severity of tinnitus and vertigo or dizziness symptoms. The online survey was completed by a German cohort of 1,082 adult Long COVID patients after a mean period of 43.2 weeks ± 23.4 weeks after infection. Eighty percent were not fully vaccinated (at least two vaccinations) at the time of their first COVID symptoms and 9.8% were hospitalized in the course of their acute SARS-CoV-2 infection. At the time of the survey, 60% of patients reported the presence of vertigo or dizziness with a mean severity of 4.6 ± 2.7 on a scale of 1 (least severe) to 10 (most severe) and 30% complained of tinnitus with a mean severity of 4.8 ± 3.0. Approximately one fifth of the participants with tinnitus and vertigo or dizziness, rated their symptoms to be severe. The data shown in this study confirms that tinnitus and vertigo or dizziness are common symptoms in Long COVID patients and demonstrates, that a compelling number of patients rate their symptoms as severe. The self-reported severity highlights the need for Long COVID clinics to address these symptoms effectively. We suggest a multidisciplinary diagnostic and therapeutic approach to prevent further morbidity and socioeconomic burden for Long COVID patients suffering from severe vertigo, dizziness or tinnitus.}, } @article {pmid35543533, year = {2022}, author = {Prasannan, N and Heightman, M and Hillman, T and Wall, E and Bell, R and Kessler, A and Neave, L and Doyle, A and Devaraj, A and Singh, D and Dehbi, HM and Scully, M}, title = {Impaired exercise capacity in post-COVID-19 syndrome: the role of VWF-ADAMTS13 axis.}, journal = {Blood advances}, volume = {6}, number = {13}, pages = {4041-4048}, pmid = {35543533}, issn = {2473-9537}, mesh = {ADAM Proteins ; ADAMTS13 Protein ; *COVID-19/complications ; Exercise Tolerance ; Humans ; SARS-CoV-2 ; *Thrombosis ; von Willebrand Factor ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID syndrome (PCS), or long COVID, is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath, and cognitive slowing. Acute COVID-19 is strongly linked with an increased risk of thrombosis, which is a prothrombotic state quantified by an elevated von Willebrand factor (VWF) antigen (Ag)/ADAMTS13 ratio that is associated with severity of acute COVID-19 infection. We investigated whether patients with PCS also had evidence of a prothrombotic state associated with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk, including VWF(Ag)/ADAMTS13 ratio, was investigated. An elevated VWF(Ag)/ADAMTS13 ratio (≥1.5) was present in nearly one-third of the cohort and was 4 times more likely to be present in patients with impaired exercise capacity, as evidenced by desaturation ≥3% and/or an increase in lactate level >1 from baseline on a 1-minute sit-to-stand test and/or a 6-minute walk test (P < .0001). Of 276 patients, 56 (20%) had impaired exercise capacity, of which 55% (31/56) had a VWF(Ag)/ADAMTS13 ratio ≥1.5 (P < .0001). Factor VIII and VWF(Ag) were elevated in 26% and 18%, respectively, and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and suggest a role for antithrombotic therapy in the treatment of these patients.}, } @article {pmid35538169, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Cancela-Cilleruelo, I and Rodríguez-Jiménez, J and Moro-López-Menchero, P and Pellicer-Valero, OJ}, title = {Exploring trajectory recovery curves of post-COVID cognitive symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study.}, journal = {Journal of neurology}, volume = {269}, number = {9}, pages = {4613-4617}, pmid = {35538169}, issn = {1432-1459}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; }, mesh = {*COVID-19/complications ; Cognition ; Hospitalization ; Humans ; Survivors/psychology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35536408, year = {2022}, author = {Papadopoulou, M and Bakola, E and Papapostolou, A and Stefanou, MI and Gaga, M and Zouvelou, V and Michopoulos, I and Tsivgoulis, G}, title = {Autonomic dysfunction in long-COVID syndrome: a neurophysiological and neurosonology study.}, journal = {Journal of neurology}, volume = {269}, number = {9}, pages = {4611-4612}, pmid = {35536408}, issn = {1432-1459}, mesh = {*Autonomic Nervous System Diseases/etiology ; *COVID-19/complications ; Heart Rate/physiology ; Humans ; *Primary Dysautonomias ; Sympathetic Nervous System/physiology ; Ultrasonography, Doppler, Transcranial ; Vagus Nerve ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35529457, year = {2022}, author = {Di Girolamo, FG and Fiotti, N and Sisto, UG and Nunnari, A and Colla, S and Mearelli, F and Vinci, P and Schincariol, P and Biolo, G}, title = {Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {865402}, pmid = {35529457}, issn = {2296-861X}, abstract = {SARS-CoV-2 infection is often associated with severe inflammation, oxidative stress, hypoxia and impaired physical activity. These factors all together contribute to muscle wasting and fatigue. In addition, there is evidence of a direct SARS-CoV-2 viral infiltration into skeletal muscle. Aging is often characterized by sarcopenia or sarcopenic obesity These conditions are risk factors for severe acute COVID-19 and long-COVID-19 syndrome. From these observations we may predict a strong association between COVID-19 and decreased muscle mass and functions. While the relationship between physical inactivity, chronic inflammation, oxidative stress and muscle dysfunction is well-known, the effects on muscle mass of COVID-19-related hypoxemia are inadequately investigated. The aim of this review is to highlight metabolic, immunity-related and redox biomarkers potentially affected by reduced oxygen availability and/or muscle fatigue in order to shed light on the negative impact of COVID-19 on muscle mass and function. Possible countermeasures are also reviewed.}, } @article {pmid35529336, year = {2022}, author = {Buonsenso, D and Munblit, D and Pazukhina, E and Ricchiuto, A and Sinatti, D and Zona, M and De Matteis, A and D'Ilario, F and Gentili, C and Lanni, R and Rongai, T and Del Balzo, P and Fonte, MT and Valente, M and Zampino, G and De Rose, C and Sigfrid, L and Valentini, P and , }, title = {Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {834875}, pmid = {35529336}, issn = {2296-2360}, abstract = {BACKGROUND: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

METHODS: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

RESULTS: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

CONCLUSION: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.}, } @article {pmid35527479, year = {2022}, author = {Allen, MB}, title = {COVID-19, cancer post-pandemic risk, and the radiation oncology physicist.}, journal = {Journal of applied clinical medical physics}, volume = {23}, number = {5}, pages = {e13628}, pmid = {35527479}, issn = {1526-9914}, mesh = {*COVID-19/epidemiology ; Health Physics ; Humans ; *Neoplasms/epidemiology/radiotherapy ; Pandemics ; *Radiation Oncology ; }, } @article {pmid35525253, year = {2022}, author = {Munblit, D and O'Hara, ME and Akrami, A and Perego, E and Olliaro, P and Needham, DM}, title = {Long COVID: aiming for a consensus.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {7}, pages = {632-634}, pmid = {35525253}, issn = {2213-2619}, mesh = {*COVID-19/complications ; Consensus ; Humans ; *Lung Neoplasms ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35524667, year = {2022}, author = {Mundula, T and Russo, E and Curini, L and Giudici, F and Piccioni, A and Franceschi, F and Amedei, A}, title = {Chronic Systemic Low-Grade Inflammation and Modern Lifestyle: The Dark Role of Gut Microbiota on Related Diseases with a Focus on COVID-19 Pandemic.}, journal = {Current medicinal chemistry}, volume = {29}, number = {33}, pages = {5370-5396}, doi = {10.2174/0929867329666220430131018}, pmid = {35524667}, issn = {1875-533X}, support = {2020//ECCO, European Crohn's and Colitis Organisation/ ; }, mesh = {*COVID-19/complications ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammation ; Life Style ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Inflammation is a physiological, beneficial, and auto-limiting response of the host to alarming stimuli. Conversely, a chronic systemic low-grade inflammation (CSLGI), known as a long-time persisting condition, causes damage to the organs and host tissues, representing a major risk for chronic diseases. Currently, a high global incidence of chronic inflammatory diseases is observed, often linked to the lifestyle-related changes that occurred in the last decade. The main lifestyle-related factors are proinflammatory diet, psychological stress, tobacco smoking, alcohol abuse, physical inactivity, and indoor living and working with its related consequences such as indoor pollution, artificial light exposure, and low vitamin D production. Recent scientific evidence found that gut microbiota (GM) has a main role in shaping the host's health, particularly as CSLGI mediator. Based on the lastest discoveries regarding the remarkable GM activity, in this manuscript we focus on the elements of actual lifestyle that influence the composition and function of the intestinal microbial community in order to elicit the CSLGI and its correlated pathologies. In this scenario, we provide a broad review of the interplay between modern lifestyle, GM, and CSLGI with a special focus on the COVID symptoms and emerging long-COVID syndrome.}, } @article {pmid35524358, year = {2022}, author = {Buonsenso, D and Piazza, M and Boner, AL and Bellanti, JA}, title = {Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome.}, journal = {Allergy and asthma proceedings}, volume = {43}, number = {3}, pages = {187-193}, pmid = {35524358}, issn = {1539-6304}, mesh = {*COVID-19/complications/physiopathology ; *Cytokines/metabolism ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production. Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition. Methods: Extensive research was conducted in medical literature data bases by applying terms such as "long COVID" associated with "persistence of the SARS-CoV-2 virus" "spike protein' "COVID-19" and "biologic therapies." Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.}, } @article {pmid35524067, year = {2022}, author = {Barrea, L and Vetrani, C and Caprio, M and Cataldi, M and Ghoch, ME and Elce, A and Camajani, E and Verde, L and Savastano, S and Colao, A and Muscogiuri, G}, title = {From the Ketogenic Diet to the Mediterranean Diet: The Potential Dietary Therapy in Patients with Obesity after CoVID-19 Infection (Post CoVID Syndrome).}, journal = {Current obesity reports}, volume = {11}, number = {3}, pages = {144-165}, pmid = {35524067}, issn = {2162-4968}, mesh = {*COVID-19 ; *Diet, Ketogenic/adverse effects ; *Diet, Mediterranean ; Humans ; Obesity/complications ; SARS-CoV-2 ; }, abstract = {PURPOSE OF REVIEW: This review primarily examines the evidence for areas of consensus and on-going uncertainty or controversy about diet and physical exercise approaches for in the post-CoVID. We propose an ideal dietary and physical activity approach that the patient with obesity should follow after CoVID-19 infection in order to reduce the clinical conditions associated with post-CoVID syndrome.

RECENT FINDINGS: The CoVID-19 disease pandemic, caused by the severe acute respiratory syndrome coronavirus-2, has spread all over the globe, infecting hundreds of millions of individuals and causing millions of death. It is also known to be is associated with several medical and psychological complications, especially in patients with obesity and weight-related disorders who in general pose a significant global public health problem, and in specific affected individuals are on a greater risk of developing poorer CoVID-19 clinical outcomes and experience a higher rate of mortality. Little is still known about the best nutritional approach to be adopted in this disease especially in the patients post-CoVID syndrome. To the best of our knowledge, no specific nutritional recommendations exist to manage in the patients post-CoVID syndrome. We report a presentation of nutritional therapeutic approach based on a ketogenic diet protocol followed by a transition to the Mediterranean diet in patients post-infection by CoVID, combined to a physical activity program to address conditions associated with post-CoVID syndrome.}, } @article {pmid35523438, year = {2022}, author = {Al-Oraibi, A and Woolf, K and Nellums, LB and Tarrant, C and Naqvi, H and Pareek, M}, title = {Caring for the carers: understanding long covid in our diverse healthcare workforce.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {o1152}, doi = {10.1136/bmj.o1152}, pmid = {35523438}, issn = {1756-1833}, support = {MR/V027549/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; *Caregivers ; Delivery of Health Care ; Humans ; Workforce ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35521969, year = {2022}, author = {de Melo, BAG and Mundim, MV and Lemes, RMR and Cruz, EM and Ribeiro, TN and Santiago, CF and da Fonsêca, JHL and Benincasa, JC and Stilhano, RS and Mantovani, N and Santana, LC and Durães-Carvalho, R and Diaz, RS and Janini, LMR and Maricato, JT and Porcionatto, MA}, title = {3D Bioprinted Neural-Like Tissue as a Platform to Study Neurotropism of Mouse-Adapted SARS-CoV-2.}, journal = {Advanced biology}, volume = {6}, number = {8}, pages = {e2200002}, pmid = {35521969}, issn = {2701-0198}, mesh = {Animals ; Brain ; *COVID-19/complications ; Humans ; Mice ; Neurons ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The effects of neuroinvasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) become clinically relevant due to the numerous neurological symptoms observed in Corona Virus Disease 2019 (COVID-19) patients during infection and post-COVID syndrome or long COVID. This study reports the biofabrication of a 3D bioprinted neural-like tissue as a proof-of-concept platform for a more representative study of SARS-CoV-2 brain infection. Bioink is optimized regarding its biophysical properties and is mixed with murine neural cells to construct a 3D model of COVID-19 infection. Aiming to increase the specificity to murine cells, SARS-CoV-2 is mouse-adapted (MA-SARS-CoV-2) in vitro, in a protocol first reported here. MA-SARS-CoV-2 reveals mutations located at the Orf1a and Orf3a domains and is evolutionarily closer to the original Wuhan SARS-CoV-2 strain than SARS-CoV-2 used for adaptation. Remarkably, MA-SARS-CoV-2 shows high specificity to murine cells, which present distinct responses when cultured in 2D and 3D systems, regarding cell morphology, neuroinflammation, and virus titration. MA-SARS-CoV-2 represents a valuable tool in studies using animal models, and the 3D neural-like tissue serves as a powerful in vitro platform for modeling brain infection, contributing to the development of antivirals and new treatments for COVID-19.}, } @article {pmid35521752, year = {2022}, author = {Busatto, GF and de Araujo, AL and Castaldelli-Maia, JM and Damiano, RF and Imamura, M and Guedes, BF and de Rezende Pinna, F and Sawamura, MVY and Mancini, MC and da Silva, KR and Garcia, ML and Sumita, N and Brunoni, AR and da Silva Duarte, AJ and Burdmann, EA and Kallas, EG and Cerri, GG and Nitrini, R and Bento, RF and Rocha, VG and de Souza, HP and Miguel, EC and de Carvalho, CRR and Forlenza, OV and Batistella, LR and , }, title = {Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.}, journal = {Psychological medicine}, volume = {52}, number = {12}, pages = {2387-2398}, pmid = {35521752}, issn = {1469-8978}, mesh = {Adult ; Aged ; C-Reactive Protein ; *COVID-19/complications ; Central Nervous System ; Disease Progression ; Fatigue/etiology ; Female ; Humans ; Inflammation ; Male ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce.

METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment.

RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities.

CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.}, } @article {pmid35514142, year = {2022}, author = {de Miranda, DAP and Gomes, SVC and Filgueiras, PS and Corsini, CA and Almeida, NBF and Silva, RA and Medeiros, MIVARC and Vilela, RVR and Fernandes, GR and Grenfell, RFQ}, title = {Long COVID-19 syndrome: a 14-months longitudinal study during the two first epidemic peaks in Southeast Brazil.}, journal = {Transactions of the Royal Society of Tropical Medicine and Hygiene}, volume = {116}, number = {11}, pages = {1007-1014}, doi = {10.1093/trstmh/trac030}, pmid = {35514142}, issn = {1878-3503}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Brazil/epidemiology ; Longitudinal Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: A growing number of long COVID cases after infection have been reported. By definition, long COVID is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, the profile and timeline of which remains uncertain.

METHODS: In this work, in-home, outpatient and hospitalized COVID-19 positive patients were monitored for up to 14 mo to establish the prevalence of long COVID symptoms and their correlation with age, pre-existing comorbidities and course of acute infection. The longitudinal study included 646 positive patients who were monitored once a month.

RESULTS: From the whole population, 50.2% presented with long COVID syndrome. Twenty-three different symptoms were reported. Most frequent were fatigue (35.6%), persistent cough (34.0%), dyspnea (26.5%), loss of smell/taste (20.1%) and frequent headaches (17.3%). Mental disorders (20.7%), change in blood pressure (7.4%) and thrombosis (6.2%) were also reported. Most patients presented with 2-3 symptoms at the same time. Long COVID started after mild, moderate and severe infection in 60, 13 and 27% of cases, respectively, and it was not restricted to specific age groups.

CONCLUSIONS: Older patients tended to have more severe symptoms, leading to a longer post-COVID-19 period. The presence of seven comorbidities was correlated with the severity of infection, and severity itself was the main factor that determined the duration of symptoms in long COVID cases.}, } @article {pmid35508067, year = {2022}, author = {Baldi, BG and Fabro, AT and Franco, AC and Machado, MHC and Prudente, RA and Franco, ET and Marrone, SR and Vale, SAD and Cezare, TJ and Moraes, MPT and Ferreira, EVM and Albuquerque, ALP and Sawamura, MVY and Tanni, SE}, title = {Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {48}, number = {3}, pages = {e20210438}, pmid = {35508067}, issn = {1806-3756}, mesh = {Biopsy/methods ; *COVID-19/complications ; Humans ; Lung/diagnostic imaging/pathology ; *Lung Diseases, Interstitial/pathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).}, } @article {pmid35507278, year = {2022}, author = {Tobler, DL and Pruzansky, AJ and Naderi, S and Ambrosy, AP and Slade, JJ}, title = {Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician.}, journal = {Current atherosclerosis reports}, volume = {24}, number = {7}, pages = {563-570}, pmid = {35507278}, issn = {1534-6242}, support = {K23 HL150159/HL/NHLBI NIH HHS/United States ; }, mesh = {*Acute Coronary Syndrome ; Arrhythmias, Cardiac ; *COVID-19/complications ; Heart ; *Heart Failure ; Humans ; SARS-CoV-2 ; *Ventricular Dysfunction, Right ; }, abstract = {PURPOSE OF REVIEW: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.

RECENT FINDINGS: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.}, } @article {pmid35505733, year = {2022}, author = {Rao, CM and Rout, P and Pattnaik, AP and Singh, N and Rajendran, A and Patro, S}, title = {The Microbial Profile and Resistance Pattern of Pathogens Isolated From Long COVID Pneumonia Patients and Their Correlation to Clinical Outcome: Our Experience From a Tertiary Care Hospital.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23644}, pmid = {35505733}, issn = {2168-8184}, abstract = {Background Coronavirus disease 2019 (COVID-19) patients with persistent symptoms for at least four weeks in spite of being reverse transcriptase-polymerase chain reaction (RTPCR) negative for COVID infection are defined as long COVID (wherein pulmonary involvement is seen in a significant proportion of cases). The history of prolonged use of corticosteroids, broad-spectrum antibiotics, and associated comorbid conditions in these patients increases the possibility of infection with multidrug-resistant microbial strains. It may lead to a grave prognosis, hence appropriate microbiological evaluation and management at the earliest can have a better outcome. Methods A retrospective observational study was carried out among long COVID patients admitted to the Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India, a tertiary care hospital. Eighty-four patients admitted to the ICU or non-ICU ward in the hospital from April to October 2021 were included in the study. Antibiotics, as prescribed by our hospital antibiotic policy, were administered wherever required and were subsequently changed according to culture and sensitivity reports of the samples (sputum, endotracheal aspirates, or blood). An analysis of the antibiotic sensitivity patterns of the pathogens isolated was performed. The outcome after optimum medical management was assessed for survivors, discharge, or death. Results Out of the total of 84 patients, 41 samples (sputum, endotracheal aspirates or blood) were collected and sent for culture, of which 32 (78.1%) were found to be culture positive for pathogens. Among the pathogens isolated, there were 22 (69%) drug-resistant and 10 (31%) sensitive organisms. Among the 22 resistant pathogen isolates, 18 were Gram-negative species, the most common species being Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii; two were Gram-positive species, one each from Staphylococcus aureus and Enterococcus faecalis, and three were Candida tropicalis. Of five deaths reported among 22 cases with resistant isolates, extensively drug-resistant (XDR), multi-drug resistance (MDR), and pan drug resistance (PDR) strains were detected in three, one, and one cases, respectively, and were harboured by K. pneumoniae, P. aeruginosa, and A. baumanii. Of the total eight deaths, there were two deaths among the 43 patients who received an empiric antibiotic in the wards, and six deaths were reported in the ICU. Despite raised biomarkers of inflammation, comorbid illnesses, renal impairment, and immunocompromised states, there was 91% survival and discharge, which was statistically significant (p-value = 0.00). Conclusion To conclude, K. pneumoniae, P. aeruginosa, A. baumanii, C. tropicalis, S. aureus, and E. faecalis were the most commonly isolated organisms among long COVID pneumonia cases, of which some were MDR, PDR and XDR strains. Early microbiological evaluation with targeted, proper antimicrobial usage along with optimized medical management and, wherever needed, critical care support in the ICU may lead to a better prognostic outcome in those groups of patients.}, } @article {pmid35501458, year = {2023}, author = {Vlachopoulos, C and Terentes-Printzios, D and Katsaounou, P and Solomou, E and Gardikioti, V and Exarchos, D and Economou, D and Christopoulou, G and Kalkinis, AD and Kafouris, P and Antonopoulos, A and Lazaros, G and Kotanidou, A and Datseris, I and Tsioufis, K and Anagnostopoulos, C}, title = {Time-related aortic inflammatory response, as assessed with [18]F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.}, journal = {Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology}, volume = {30}, number = {1}, pages = {74-82}, pmid = {35501458}, issn = {1532-6551}, mesh = {Humans ; Middle Aged ; Aged ; *Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Case-Control Studies ; Radiopharmaceuticals ; *COVID-19 ; Positron-Emission Tomography ; Aorta, Abdominal ; Inflammation ; }, abstract = {AIM: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19.

METHODS: Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring [18]F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR.

RESULTS: There was no significant difference in aortic [18]F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to [18]F-FDG PET-CT scan (Spearman's rho = - 0.528, P = 0.017 and Spearman's rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036).

CONCLUSION: This is the first study suggesting that aortic inflammation, as assessed by [18]F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.}, } @article {pmid35496469, year = {2022}, author = {Hafiz, R and Gandhi, TK and Mishra, S and Prasad, A and Mahajan, V and Di, X and Natelson, BH and Biswal, BB}, title = {Higher limbic and basal ganglia volumes in surviving COVID-negative patients and the relations to fatigue.}, journal = {Neuroimage. Reports}, volume = {2}, number = {2}, pages = {100095}, pmid = {35496469}, issn = {2666-9560}, support = {R01 AT009829/AT/NCCIH NIH HHS/United States ; R01 MH131335/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Among systemic abnormalities caused by the novel coronavirus, little is known about the critical attack on the central nervous system (CNS). Few studies have shown cerebrovascular pathologies that indicate CNS involvement in acute patients. However, replication studies are necessary to verify if these effects persist in COVID-19 survivors more conclusively. Furthermore, recent studies indicate fatigue is highly prevalent among 'long-COVID' patients. How morphometry in each group relate to work-related fatigue need to be investigated.

METHOD: COVID survivors were MRI scanned two weeks after hospital discharge. We hypothesized, these survivors will demonstrate altered gray matter volume (GMV) and experience higher fatigue levels when compared to healthy controls, leading to stronger correlation of GMV with fatigue. Voxel-based morphometry was performed on T1-weighted MRI images between 46 survivors and 30 controls. Unpaired two-sample t-test and multiple linear regression were performed to observe group differences and correlation of fatigue with GMV.

RESULTS: The COVID group experienced significantly higher fatigue levels and GMV of this group was significantly higher within the Limbic System and Basal Ganglia when compared to healthy controls. Moreover, while a significant positive correlation was observed across the whole group between GMV and self-reported fatigue, COVID subjects showed stronger effects within the Posterior Cingulate, Precuneus and Superior Parietal Lobule.

CONCLUSION: Brain regions with GMV alterations in our analysis align with both single case acute patient reports and current group level neuroimaging findings. We also newly report a stronger positive correlation of GMV with fatigue among COVID survivors within brain regions associated with fatigue, indicating a link between structural abnormality and brain function in this cohort.}, } @article {pmid35496309, year = {2022}, author = {Spuch, C and López-García, M and Rivera-Baltanás, T and Cabrera-Alvargonzález, JJ and Gadh, S and Rodrigues-Amorim, D and Álvarez-Estévez, T and Mora, A and Iglesias-Martínez-Almeida, M and Freiría-Martínez, L and Pérez-Rodríguez, M and Pérez-González, A and López-Domínguez, A and Longueira-Suarez, MR and Sousa-Domínguez, A and Araújo-Ameijeiras, A and Mosquera-Rodríguez, D and Crespo, M and Vila-Fernández, D and Regueiro, B and Olivares, JM}, title = {Efficacy and Safety of Lithium Treatment in SARS-CoV-2 Infected Patients.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {850583}, pmid = {35496309}, issn = {1663-9812}, abstract = {At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020-002008-37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.}, } @article {pmid35493814, year = {2022}, author = {Hirano, SI and Ichikawa, Y and Sato, B and Takefuji, Y and Satoh, F}, title = {Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review.}, journal = {Frontiers in neurology}, volume = {13}, number = {}, pages = {841310}, pmid = {35493814}, issn = {1664-2295}, abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disorder that is characterized by fatigue that persists for more than 6 months, weakness, sleep disturbances, and cognitive dysfunction. There are multiple possible etiologies for ME/CFS, among which mitochondrial dysfunction plays a major role in abnormal energy metabolism. The potential of many substances for the treatment of ME/CFS has been examined; however, satisfactory outcomes have not yet been achieved. The development of new substances for curative, not symptomatic, treatments is desired. Molecular hydrogen (H2) ameliorates mitochondrial dysfunction by scavenging hydroxyl radicals, the most potent oxidant among reactive oxygen species. Animal experiments and clinical trials reported that H2 exerted ameliorative effects on acute and chronic fatigue. Therefore, we conducted a literature review on the mechanism by which H2 improves acute and chronic fatigue in animals and healthy people and showed that the attenuation of mitochondrial dysfunction by H2 may be involved in the ameliorative effects. Although further clinical trials are needed to determine the efficacy and mechanism of H2 gas in ME/CFS, our literature review suggested that H2 gas may be an effective medical gas for the treatment of ME/CFS.}, } @article {pmid35493431, year = {2022}, author = {Efstathiou, V and Stefanou, MI and Demetriou, M and Siafakas, N and Makris, M and Tsivgoulis, G and Zoumpourlis, V and Kympouropoulos, SP and Tsoporis, JN and Spandidos, DA and Smyrnis, N and Rizos, E}, title = {Long COVID and neuropsychiatric manifestations (Review).}, journal = {Experimental and therapeutic medicine}, volume = {23}, number = {5}, pages = {363}, pmid = {35493431}, issn = {1792-1015}, abstract = {There is accumulating evidence in the literature indicating that a number of patients with coronavirus disease 2019 (COVID-19) may experience a range of neuropsychiatric symptoms, persisting or even presenting following the resolution of acute COVID-19. Among the neuropsychiatric manifestations more frequently associated with 'long COVID' are depression, anxiety, post-traumatic stress disorder, sleep disturbances, fatigue and cognitive deficits, that can potentially be debilitating and negatively affect patients' wellbeing, albeit in the majority of cases symptoms tend to improve over time. Despite variations in results obtained from studies using different methodological approaches to define 'long COVID' syndrome, the most widely accepted factors associated with a higher risk of developing neuropsychiatric manifestations include the severity of foregoing COVID-19, the female sex, the presence of comorbidities, a history of mental health disease and an elevation in the levels of inflammatory markers, albeit further research is required to establish causal associations. To date, the pathophysiological mechanisms implicated in neuropsychiatric manifestations of 'long COVID' remain only partially elucidated, while the role of the indirect effects of the COVID-19 pandemic, such as social isolation and uncertainty concerning social, financial and health recovery post-COVID, have also been highlighted. Given the alarming effects of 'long-COVID', interdisciplinary cooperation for the early identification of patients who are at a high risk of persistent neuropsychiatric presentations, beyond COVID-19 recovery, is crucial to ensure that appropriate integrated physical and mental health support is provided, with the aim of mitigating the risks of long-term disability at a societal and individual level.}, } @article {pmid35492595, year = {2022}, author = {Dos Santos, PK and Sigoli, E and Bragança, LJG and Cornachione, AS}, title = {The Musculoskeletal Involvement After Mild to Moderate COVID-19 Infection.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {813924}, pmid = {35492595}, issn = {1664-042X}, abstract = {COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has been drastically affecting the daily lives of millions of people. COVID-19 is described as a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and skeletal muscle damage. These symptoms can persist for months, decreasing the quality of life of numerous individuals. Curiously, most studies in the scientific literature focus on patients who were hospitalized due to SARS-CoV-2 infection and little is known about the mechanism of action of COVID-19 on skeletal muscles, especially of individuals who had the mild to moderate forms of the disease (non-hospitalized patients). In this review, we focus on the current knowledge about the musculoskeletal system in COVID-19, highlighting the lack of researches investigating the mild to moderate cases of infection and pointing out why it is essential to care for these patients. Also, we will comment about the need of more experimental data to assess the musculoskeletal manifestations on COVID-19-positive individuals.}, } @article {pmid35491089, year = {2022}, author = {Sunada, N and Honda, H and Nakano, Y and Yamamoto, K and Tokumasu, K and Sakurada, Y and Matsuda, Y and Hasegawa, T and Otsuka, Y and Obika, M and Hanayama, Y and Hagiya, H and Ueda, K and Kataoka, H and Otsuka, F}, title = {Hormonal trends in patients suffering from long COVID symptoms.}, journal = {Endocrine journal}, volume = {69}, number = {10}, pages = {1173-1181}, doi = {10.1507/endocrj.EJ22-0093}, pmid = {35491089}, issn = {1348-4540}, mesh = {Humans ; Female ; Aged ; Thyrotropin ; *COVID-19 ; Hydrocortisone ; Retrospective Studies ; Dysgeusia ; SARS-CoV-2 ; *Olfaction Disorders ; Alopecia ; Fatigue/epidemiology/etiology ; Thyroxine ; Post-Acute COVID-19 Syndrome ; }, abstract = {Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.}, } @article {pmid35490909, year = {2022}, author = {Mungmunpuntipantip, R and Wiwanitkit, V}, title = {Letter on the article "Long-COVID: Cognitive deficits (brain fog) and brain lesions in nonhospitalized patients".}, journal = {Presse medicale (Paris, France : 1983)}, volume = {51}, number = {2}, pages = {104122}, pmid = {35490909}, issn = {2213-0276}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Cognition Disorders/etiology ; *Nervous System Diseases ; Brain/diagnostic imaging ; Cognition ; }, } @article {pmid35490117, year = {2022}, author = {Zürcher, SJ and Banzer, C and Adamus, C and Lehmann, AI and Richter, D and Kerksieck, P}, title = {Post-viral mental health sequelae in infected persons associated with COVID-19 and previous epidemics and pandemics: Systematic review and meta-analysis of prevalence estimates.}, journal = {Journal of infection and public health}, volume = {15}, number = {5}, pages = {599-608}, pmid = {35490117}, issn = {1876-035X}, mesh = {Adult ; *COVID-19/epidemiology ; Humans ; *Influenza A Virus, H1N1 Subtype ; *Influenza A Virus, H7N9 Subtype ; Mental Health ; Pandemics ; Prevalence ; SARS-CoV-2 ; }, abstract = {AIMS: Post-viral mental health problems (MHP) in COVID-19 patients and survivors were anticipated already during early stages of this pandemic. We aimed to synthesize the prevalence of the anxiety, depression, post-traumatic and general distress domain associated with virus epidemics since 2002.

METHODS: In this systematic review and meta-analysis, we searched PubMed, PsycINFO, and Embase from 2002 to April 14, 2021 for peer-reviewed studies reporting prevalence of MHP in adults with laboratory-confirmed or suspected SARS-CoV-1, H1N1, MERS-CoV, H7N9, Ebolavirus, or SARS-CoV-2 infection. We included studies that assessed post-viral MHP with validated and frequently used scales. A three-level random-effects meta-analysis for dependent effect sizes was conducted to account for multiple outcome reporting. We pooled MHP across all domains and separately by severity (above mild or moderate-to-severe) and by acute (one month), ongoing (one to three months), and post-illness stages (longer than three months). A meta-regression was conducted to test for moderating effects, particularly for exploring estimate differences between SARS-Cov-2 and previous pandemics and epidemics. PROSPERO registration: CRD42020194535.

RESULTS: We identified 59 studies including between 14 and 1002 participants and providing 187 prevalence estimates. MHP, in general, decreased from acute to post-illness from 46.3% to 38.8% and for mild and moderate-to-severe from 22.3% to 18.8%, respectively. We found no evidence of moderating effects except for non-random sampling and H1N1 showing higher prevalence. There was a non-significant trend towards lower MHP for SARS-CoV-2 compared to previous epidemics.

CONCLUSIONS: MHP prevalence estimates decreased over time but were still on a substantial level at post-illness. Post-viral mental health problems caused by SARS-CoV-2 could have been expected much earlier, given the previous post-viral sequelae.}, } @article {pmid35489367, year = {2022}, author = {Philip, KEJ and Owles, H and McVey, S and Pagnuco, T and Bruce, K and Brunjes, H and Banya, W and Mollica, J and Lound, A and Zumpe, S and Abrahams, AM and Padmanaban, V and Hardy, TH and Lewis, A and Lalvani, A and Elkin, S and Hopkinson, NS}, title = {An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {9}, pages = {851-862}, pmid = {35489367}, issn = {2213-2619}, mesh = {*COVID-19/complications ; Dyspnea/etiology/therapy ; Humans ; Quality of Life ; Single-Blind Method ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: There are few evidence-based interventions for long COVID; however, holistic approaches supporting recovery are advocated. We assessed whether an online breathing and wellbeing programme improves health related quality-of-life (HRQoL) in people with persisting breathlessness following COVID-19.

METHODS: We conducted a parallel-group, single-blind, randomised controlled trial in patients who had been referred from one of 51 UK-based collaborating long COVID clinics. Eligible participants were aged 18 years or older; were recovering from COVID-19 with ongoing breathlessness, with or without anxiety, at least 4 weeks after symptom onset; had internet access with an appropriate device; and were deemed clinically suitable for participation by one of the collaborating COVID-19 clinics. Following clinical assessment, potential participants were given a unique online portal code. Participants were randomly assigned (1:1) to either immediate participation in the English National Opera (ENO) Breathe programme or to usual care. Randomisation was done by the research team using computer-generated block randomisation lists, with block size 10. The researcher responsible for randomisation was masked to responses. Participants in the ENO Breathe group participated in a 6-week online breathing and wellbeing programme, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques. Those in the deferred group received usual care until they exited the trial. The primary outcome, assessed in the intention-to-treat population, was change in HRQoL, assessed using the RAND 36-item short form survey instrument mental health composite (MHC) and physical health composite (PHC) scores. Secondary outcome measures were the chronic obstructive pulmonary disease assessment test score, visual analogue scales (VAS) for breathlessness, and scores on the dyspnoea-12, the generalised anxiety disorder 7-item scale, and the short form-6D. A thematic analysis exploring participant experience was also conducted using qualitative data from focus groups, survey responses, and email correspondence. This trial is registered with ClinicalTrials.gov, NCT04830033.

FINDINGS: Between April 22 and May 25, 2021, 158 participants were recruited and randomly assigned. Of these, eight (5%) individuals were excluded and 150 participants were allocated to a treatment group (74 in the ENO Breathe group and 76 in the usual care group). Compared with usual care, ENO Breathe was associated with an improvement in MHC score (regression coefficient 2·42 [95% CI 0·03 to 4·80]; p=0·047), but not PHC score (0·60 [-1·33 to 2·52]; p=0·54). VAS for breathlessness (running) favoured ENO Breathe participation (-10·48 [-17·23 to -3·73]; p=0·0026). No other statistically significant between-group differences in secondary outcomes were observed. One minor self-limiting adverse event was reported by a participant in the ENO Breathe group who felt dizzy using a computer for extended periods. Thematic analysis of ENO Breathe participant experience identified three key themes: (1) improvements in symptoms; (2) feeling that the programme was complementary to standard care; and (3) the particular suitability of singing and music to address their needs.

INTERPRETATION: Our findings suggest that an online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable, symptom-management techniques might have a role supporting recovery.

FUNDING: Imperial College London.}, } @article {pmid35489015, year = {2022}, author = {Umesh, A and Pranay, K and Pandey, RC and Gupta, MK}, title = {Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism.}, journal = {Infection}, volume = {50}, number = {5}, pages = {1053-1066}, pmid = {35489015}, issn = {1439-0973}, mesh = {*COVID-19/complications/epidemiology ; Hospitalization ; Humans ; Risk Factors ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Apart from the global disease burden of acute COVID-19 disease, the health complications arising after recovery have been recognized as a long-COVID or post-COVID-19 syndrome. Evidences of long-COVID symptoms involving various organ systems are rapidly growing in literature. The objective was to perform a rapid review and evidence mapping of systemic complications and symptoms of long-COVID and underlying pathophysiological mechanisms.

METHODS: Publications reporting clinical trials, observational cohort studies, case-control studies, case-series, meta-analysis, and systematic reviews, focusing on the squeal of the disease, consequences of COVID-19 treatment/hospitalization, long-COVID, chronic COVID syndrome, and post acute COVID-19 were reviewed in detail for the narrative synthesis of frequency, duration, risk factors, and pathophysiology.

RESULTS: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies. However, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood. Analysis of the clinical trial landscape suggests that more than 50% of the industry-sponsored trials are focused on pulmonary symptoms. In contrast to the epidemiological trends and academic trials, cardiovascular complications are not a focus of industry-sponsored trials, suggestive of the gaps in the research efforts.

CONCLUSION: The gap in epidemiological trends and academic trials, particularly concerning cardiovascular complications not being a focus of industry-sponsored trials is suggestive of the gaps in research efforts and longer follow-up durations would help identify other long-COVID-related health issues such as reproductive health and fertility.}, } @article {pmid35488918, year = {2022}, author = {Calabria, M and García-Sánchez, C and Grunden, N and Pons, C and Arroyo, JA and Gómez-Anson, B and Estévez García, MDC and Belvís, R and Morollón, N and Vera Igual, J and Mur, I and Pomar, V and Domingo, P}, title = {Post-COVID-19 fatigue: the contribution of cognitive and neuropsychiatric symptoms.}, journal = {Journal of neurology}, volume = {269}, number = {8}, pages = {3990-3999}, pmid = {35488918}, issn = {1432-1459}, mesh = {*COVID-19/complications ; Cognition ; *Cognitive Dysfunction/diagnosis ; Depression/diagnosis ; Fatigue/diagnosis ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as "Long COVID." Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue.}, } @article {pmid35487533, year = {2022}, author = {Di Mattei, VE and Perego, G and Milano, F and Hill, TE and Harari, SA}, title = {The curious incident of long COVID symptoms, from an imaginary condition to a recognised syndrome: a "small victory".}, journal = {The European respiratory journal}, volume = {59}, number = {6}, pages = {}, pmid = {35487533}, issn = {1399-3003}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {In the early stages of the pandemic, patients with a post-COVID condition felt ignored and disbelieved by their doctors and relatives. Given the importance of the doctor–patient relationship in post-COVID management, we recommend “relationship-based care”. https://bit.ly/3vQ9RO1}, } @article {pmid35486940, year = {2022}, author = {Gupta, M and Gupta, N and Esang, M}, title = {Long COVID in Children and Adolescents.}, journal = {The primary care companion for CNS disorders}, volume = {24}, number = {2}, pages = {}, doi = {10.4088/PCC.21r03218}, pmid = {35486940}, issn = {2155-7780}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Objective: To review the empirical evidence regarding neuropsychiatric illness (long coronavirus disease [COVID]) in children and adolescents post-severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection. Data Sources: A search of PubMed, PsycINFO, Cochrane Library, and Google Scholar was conducted from the date of inception until February 2022 using the keywords corona*, COVID-19, SARS-CoV-2, mental health, depression, anxiety, neurological, psychiatric, long COVID, and post-COVID outcomes. Age filters were used to include children and adolescents aged ≤ 18 years. Study Selection: The search resulted in the identification of 526 articles; 48 articles met the inclusion criteria. Data Extraction: Results are presented using a narrative review format. Data regarding long COVID in children and adolescents post-SARS-CoV-2 infection were extracted to understand epidemiologic trends, preventive measures, and treatment options. Results: Studies during the initial phase of the pandemic reported a mixed range of symptoms from case reports or case series. However, multisystem inflammatory syndrome in children (MIS-C) was widely reported. During the subsequent phases, the emergence of new variants led to a surge of SARS-CoV-2 infections in pediatric populations. There were highly variable, mixed symptom clusters within 60 days post-infection, which resolved in many patients within 6 months. There were prolonged illnesses and impairments in some children and adolescents with long COVID, and many had similar symptoms even though they tested negative for COVID-19. Conclusions: Long COVID symptoms are both physical and mental in nature among children and adolescents. The impairments have the potential to affect long-term functioning and increase the overall burden on health care delivery. Despite current studies having methodological issues, there is a consensus to provide multidisciplinary and holistic care to those in need.}, } @article {pmid35484639, year = {2022}, author = {Weinstock, LB and Brook, JB and Walters, AS and Goris, A and Afrin, LB and Molderings, GJ}, title = {Restless legs syndrome is associated with long-COVID in women.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {18}, number = {5}, pages = {1413-1418}, pmid = {35484639}, issn = {1550-9397}, mesh = {Adult ; *COVID-19/complications ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Pregnancy ; *Pregnancy Complications, Infectious ; Quality of Life ; *Restless Legs Syndrome/complications/diagnosis/epidemiology ; Retrospective Studies ; *Sleep Apnea Syndromes/complications ; *Sleep Wake Disorders/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {STUDY OBJECTIVES: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-coronavirus disease 2019 (pre-COVID-19) time points.

METHODS: Adults on LC-focused Facebook pages were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥ 18 years of age who never had overt symptoms of COVID-19. Pregnancy was an exclusion criterion for both groups.

RESULTS: There were 136 participants with LC (89.7% females, age 46.9 ± 12.9 years) and 136 controls (65.4% females, age 49.2 ± 15.5). RLS prevalence in females with LC was 5.7% pre-COVID-19 and 14.8% post-COVID-19 (P < .01) vs 6.7% in control females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among females with LC failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity, or use of antihistamines and antidepressants.

CONCLUSIONS: The baseline prevalence of RLS in females with LC was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Postinfectious immunological mechanisms may be at play in the production for RLS symptoms.

CITATION: Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med. 2022;18(5):1413-1418.}, } @article {pmid35478078, year = {2022}, author = {Ziegler, S and Raineri, A and Nittas, V and Rangelov, N and Vollrath, F and Britt, C and Puhan, MA}, title = {Long COVID Citizen Scientists: Developing a Needs-Based Research Agenda by Persons Affected by Long COVID.}, journal = {The patient}, volume = {15}, number = {5}, pages = {565-576}, pmid = {35478078}, issn = {1178-1661}, mesh = {Adolescent ; Adult ; *COVID-19/complications/epidemiology ; Child ; *Fatigue Syndrome, Chronic/epidemiology ; Female ; Humans ; Male ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-term health consequences following acute SARS-CoV-2 infection, referred to as post-COVID-19 condition or Long COVID, are increasing, with population-based prevalence estimates for adults at around 20%. Persons affected by Long COVID report various health problems, yet evidence to guide clinical decision making remains scarce.

OBJECTIVE: The present study aimed to identify Long COVID research priorities using a citizen science approach and solely considering the needs of those affected.

METHODS: This citizen science study followed an iterative process of patient needs identification, evaluation and prioritisation. A Long COVID Citizen Science Board (21 persons with Long COVID, and seven with myalgic encephalomyelitis/chronic fatigue syndrome) and a Long COVID Working Group (25 persons with Long COVID, four patients with myalgic encephalomyelitis/chronic fatigue syndrome and one relative) were formed. The study included four activities: three remote meetings and one online survey. First, Board members identified the needs and research questions. Second, Working Group members and persons affected by Long COVID (241 respondents, 85.5% with Long COVID, 14.5% with myalgic encephalomyelitis/chronic fatigue syndrome and 7.1% relatives) evaluated the research questions on a 1-5 Likert scale using an online survey. Then the Board gave feedback on this evaluation. Finally, Board members set the priorities for research through voting and discussion.

RESULTS: Sixty-eight research questions were generated by the Board and categorised into four research domains (medicine, healthcare services, socioeconomics and burden of disease) and 14 subcategories. Their average importance ratings were moderate to high and varied from 3.41 (standard deviation = 1.16) for sex-specific diagnostics to 4.86 (standard deviation = 0.41) for medical questions on treatment. Five topics were prioritised: "treatment, rehabilitation and chronic care management", "availability of interfaces for treatment continuity", "availability of healthcare structures", "awareness and knowledge among professionals" and "prevalence of Long COVID in children and adolescents".

CONCLUSIONS: To our knowledge, this is the first study developing a citizen-driven, explicitly patient-centred research agenda with persons affected by Long COVID, setting it apart from existing multi-stakeholder efforts. The identified priorities could guide future research and funding allocation. Our methodology establishes a framework for citizen-driven research agendas, suitable for transfer to other diseases.}, } @article {pmid35477864, year = {2022}, author = {Lin, S and Lau, LH and Chanchlani, N and Kennedy, NA and Ng, SC}, title = {Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic.}, journal = {Gut}, volume = {71}, number = {7}, pages = {1426-1439}, pmid = {35477864}, issn = {1468-3288}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; COVID-19 Vaccines ; Chronic Disease ; Humans ; *Inflammatory Bowel Diseases/complications/drug therapy/epidemiology ; Pandemics/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has raised considerable concerns that patients with inflammatory bowel disease (IBD), particularly those treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 acquisition, develop worse outcomes following COVID-19, and have suboptimal vaccine response compared with the general population. In this review, we summarise data on the risk of COVID-19 and associated outcomes, and latest guidance on SARS-CoV-2 vaccines in patients with IBD. Emerging evidence suggests that commonly used medications for IBD, such as corticosteroids but not biologicals, were associated with adverse outcomes to COVID-19. There has been no increased risk of de novo, or delayed, IBD diagnoses, however, an overall decrease in endoscopy procedures has led to a rise in the number of missed endoscopic-detected cancers during the pandemic. The impact of IBD medication on vaccine response has been a research priority recently. Data suggest that patients with IBD treated with antitumour necrosis factor (TNF) medications had attenuated humoral responses to SARS-CoV-2 vaccines, and more rapid antibody decay, compared with non-anti-TNF-treated patients. Reassuringly, rates of breakthrough infections and hospitalisations in all patients who received vaccines, irrespective of IBD treatment, remained low. International guidelines recommend that all patients with IBD treated with immunosuppressive therapies should receive, at any point during their treatment cycle, three primary doses of SARS-CoV-2 vaccines with a further booster dose as soon as possible. Future research should focus on our understanding of the rate of antibody decay in biological-treated patients, which patients require additional doses of SARS-CoV-2 vaccine, the long-term risks of COVID-19 on IBD disease course and activity, and the potential risk of long COVID-19 in patients with IBD.}, } @article {pmid35477524, year = {2022}, author = {Hughes, SE and Haroon, S and Subramanian, A and McMullan, C and Aiyegbusi, OL and Turner, GM and Jackson, L and Davies, EH and Frost, C and McNamara, G and Price, G and Matthews, K and Camaradou, J and Ormerod, J and Walker, A and Calvert, MJ}, title = {Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.}, journal = {BMJ (Clinical research ed.)}, volume = {377}, number = {}, pages = {e070230}, pmid = {35477524}, issn = {1756-1833}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Humans ; Prospective Studies ; Reproducibility of Results ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).

DESIGN: Multiphase, prospective mixed methods study.

SETTING: Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.

PARTICIPANTS: 13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.

MAIN OUTCOME MEASURES: Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.

RESULTS: SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.

CONCLUSIONS: SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.}, } @article {pmid35474919, year = {2022}, author = {Kerbl, R}, title = {[Long COVID?].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {170}, number = {6}, pages = {490-492}, doi = {10.1007/s00112-022-01484-x}, pmid = {35474919}, issn = {0026-9298}, } @article {pmid35474749, year = {2022}, author = {Blomberg, B and Cox, RJ and Langeland, N}, title = {Long COVID: A growing problem in need of intervention.}, journal = {Cell reports. Medicine}, volume = {3}, number = {3}, pages = {100552}, pmid = {35474749}, issn = {2666-3791}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Public Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {The number of people who have survived COVID-19 is overwhelming-official figures approach half a billion. Thus, any long-term consequences in COVID-19 survivors could have a huge impact on public health and on healthcare services in the coming months and years, with potentially 100 million individuals affected.}, } @article {pmid35473737, year = {2022}, author = {Haroon, S and Nirantharakumar, K and Hughes, SE and Subramanian, A and Aiyegbusi, OL and Davies, EH and Myles, P and Williams, T and Turner, G and Chandan, JS and McMullan, C and Lord, J and Wraith, DC and McGee, K and Denniston, AK and Taverner, T and Jackson, LJ and Sapey, E and Gkoutos, G and Gokhale, K and Leggett, E and Iles, C and Frost, C and McNamara, G and Bamford, A and Marshall, T and Zemedikun, DT and Price, G and Marwaha, S and Simms-Williams, N and Brown, K and Walker, A and Jones, K and Matthews, K and Camaradou, J and Saint-Cricq, M and Kumar, S and Alder, Y and Stanton, DE and Agyen, L and Baber, M and Blaize, H and Calvert, M}, title = {Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).}, journal = {BMJ open}, volume = {12}, number = {4}, pages = {e060413}, pmid = {35473737}, issn = {2044-6055}, support = {MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MR/P021220/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications/therapy ; COVID-19 Testing ; Humans ; Patient Reported Outcome Measures ; Quality of Life ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.

METHODS AND ANALYSIS: A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

TRIAL REGISTRATION NUMBER: 1567490.}, } @article {pmid35472305, year = {2022}, author = {Florencio, LL and Fernández-de-Las-Peñas, C}, title = {Long COVID: systemic inflammation and obesity as therapeutic targets.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {8}, pages = {726-727}, pmid = {35472305}, issn = {2213-2619}, mesh = {*COVID-19/complications ; Humans ; Inflammation/drug therapy ; Obesity/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35472304, year = {2022}, author = {, }, title = {Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {8}, pages = {761-775}, pmid = {35472304}, issn = {2213-2619}, support = {MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MR/S004041/1/MRC_/Medical Research Council/United Kingdom ; G0501425/MRC_/Medical Research Council/United Kingdom ; 206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MR/T005580/1/MRC_/Medical Research Council/United Kingdom ; SP/14/6/31350/BHF_/British Heart Foundation/United Kingdom ; G0801952/MRC_/Medical Research Council/United Kingdom ; G108/603/MRC_/Medical Research Council/United Kingdom ; G0700859/MRC_/Medical Research Council/United Kingdom ; FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20002/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; CH/16/1/32013/BHF_/British Heart Foundation/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_00008/5/MRC_/Medical Research Council/United Kingdom ; MR/J002739/1/MRC_/Medical Research Council/United Kingdom ; 216606/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; MR/V034243/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/N029488/1/MRC_/Medical Research Council/United Kingdom ; G1000191/MRC_/Medical Research Council/United Kingdom ; MC_PC_20016/MRC_/Medical Research Council/United Kingdom ; 209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Adult ; *COVID-19/complications/therapy ; Female ; Hospitalization ; Humans ; Inflammation ; Longitudinal Studies ; Male ; Middle Aged ; Obesity ; Prospective Studies ; Quality of Life ; Retrospective Studies ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.

METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.

FINDINGS: 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7-9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46-0·99]), obesity (0·50 [0·34-0·74]) and invasive mechanical ventilation (0·42 [0·23-0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74-1·00]), at 5 months (0·74 [0·64-0·88]) to 1 year (0·75 [0·62-0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.

INTERPRETATION: The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

FUNDING: UK Research and Innovation and National Institute for Health Research.}, } @article {pmid35468586, year = {2022}, author = {Al-Jabr, H and Windle, K and Thompson, DR and Jenkins, ZM and Castle, DJ and Ski, CF}, title = {Long COVID Optimal Health Program (LC-OHP) to Enhance Psychological and Physical Health: Protocol for a Feasibility Randomized Controlled Trial.}, journal = {JMIR research protocols}, volume = {11}, number = {5}, pages = {e36673}, pmid = {35468586}, issn = {1929-0748}, abstract = {BACKGROUND: Long COVID is a collection of symptoms that develop during or following a confirmed or suspected case of COVID-19, which continue for more than 12 weeks. Despite the negative impact of long COVID on people's lives and functioning, there is no validated treatment or even rehabilitation guidance. What has been recommended thus far is the adoption of holistic management approaches. The Optimal Health Program (OHP) is a brief 5-session, plus booster, psychosocial program designed to support mental and physical well-being that has been used effectively for a range of chronic conditions.

OBJECTIVE: This study examines the feasibility and acceptability of employing an especially customized version of OHP (long COVID OHP [LC-OHP]) to improve psychological and physical health of people with long COVID.

METHODS: This is a feasibility randomized controlled trial that will be running from November 2021 to February 2023. Eligible participants aged 18 years or older who are experiencing symptoms of long COVID will be identified through their secondary practitioners with recruitment to be undertaken by the research team. A total of 60 participants will be randomized into a control (usual care) or an intervention (LC-OHP) group. Outcomes will be feasibility and acceptability of the program (primary); and efficacy of the LC-OHP in improving anxiety, depression, fatigue, self-efficacy, and quality of life (secondary). Up to 20 participants will be interviewed at the end of the trial to explore their experience with the program. Quantitative data will be analyzed using SPSS, and differences between groups will be compared using inferential tests where appropriate. Qualitative data will be transcribed and thematically analyzed to identify common emerging themes.

RESULTS: This is an ongoing study, which began in November 2021.

CONCLUSIONS: Long COVID has a significant impact on an individual's mental and physical functioning. The LC-OHP has a potential to provide people living with long COVID with additional support and to improve self-efficacy. The findings of this study would identify the feasibility of delivering this program to this population and will provide an indication for the program's effectiveness.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN38746119; https://www.isrctn.com/ISRCTN38746119.

DERR1-10.2196/36673.}, } @article {pmid35468083, year = {2022}, author = {Day, HLS}, title = {Exploring Online Peer Support Groups for Adults Experiencing Long COVID in the United Kingdom: Qualitative Interview Study.}, journal = {Journal of medical Internet research}, volume = {24}, number = {5}, pages = {e37674}, pmid = {35468083}, issn = {1438-8871}, mesh = {Adult ; *COVID-19/complications ; Humans ; Peer Group ; Qualitative Research ; Self-Help Groups ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is an emerging public health concern. A growing number of individuals are experiencing prolonged, multifaceted health challenges and accompanying social impacts after COVID-19 infections. Support services in the United Kingdom remain insufficient and fraught with complexity. Responding to persistent gaps in care, patients joined forces in online peer support groups. However, little is known about how these groups impact patients with long COVID and their lived experiences of the condition.

OBJECTIVE: The aim of this study is to explore the roles that online peer support groups take on and the impact they have on patients experiencing and recovering from long COVID in the United Kingdom. In doing so, this study aims to identify ways to inform future long COVID care, including online peer support and broader long COVID care structures.

METHODS: I conducted 11 semistructured interviews virtually on Zoom in July 2021. Participants had long COVID, were UK-based, and used long COVID online peer support groups. Topics discussed in interviews included what led participants to these groups, experiences within them, and feelings about the roles that the groups took on. I analyzed the results by manually conducting thematic analysis.

RESULTS: Long COVID online peer support groups had numerous roles, significantly impacting users. I identified 5 themes and 13 subthemes through thematic analysis. The identified themes were as follows: (1) filling professional care gaps, (2) societal awareness, (3) engagement behavior, (4) diversity, and (5) social connections. Given the void of professional support, those experiencing long COVID gained some benefit from these groups. However, participants emphasized notable concerns about the all-encompassing roles these groups embody and speculated over potential improvements.

CONCLUSIONS: If used appropriately, online peer support groups could be immensely beneficial for patient well-being, beyond simply filling gaps in long COVID care. However, it appears many groups take on more than they can manage and become potentially harmful. Through prioritizing patient voices, long COVID care could be restructured to maximize peer support's benefits within broader care structures.}, } @article {pmid35467330, year = {2022}, author = {Martin-Lesende, I and Blasco-López, L}, title = {Emotional and psychological impact of infection and postCOVID-19 in older people: beyond the usual symptoms of long COVID.}, journal = {European geriatric medicine}, volume = {13}, number = {3}, pages = {693-694}, pmid = {35467330}, issn = {1878-7649}, mesh = {Aged ; *COVID-19/complications/epidemiology ; Emotions ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35466278, year = {2022}, author = {Lazova, S and Dimitrova, Y and Hristova, D and Tzotcheva, I and Velikova, T}, title = {Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C-Can We Match the Puzzle?.}, journal = {Antibodies (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {35466278}, issn = {2073-4468}, abstract = {The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first.}, } @article {pmid35465246, year = {2022}, author = {McCarthy, MJ}, title = {Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19.}, journal = {Brain, behavior, & immunity - health}, volume = {20}, number = {}, pages = {100412}, pmid = {35465246}, issn = {2666-3546}, abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a common and disabling disorder primarily characterized by persistent fatigue and exercise intolerance, with associated sleep disturbances, autonomic dysfunction, and cognitive problems. The causes of ME/CFS are not well understood but may coincide with immune and inflammatory responses following viral infections. During the current SARS-CoV2 coronavirus pandemic, ME/CFS has been increasingly reported to overlap with persistent "long COVID" symptoms, also called the post-acute sequelae of COVID-19 (PASC). Given the prominence of activity and sleep problems in ME/CFS, circadian rhythm disruption has been examined as a contributing factor in ME/CFS. While these studies of circadian rhythms have been pursued for decades, evidence linking circadian rhythms to ME/CFS remains inconclusive. A major limitation of older chronobiology studies of ME/CFS was the unavailability of modern molecular methods to study circadian rhythms and incomplete understanding of circadian rhythms outside the brain in peripheral organ systems. Major methodological and conceptual advancements in chronobiology have since been made. Over the same time, biomarker research in ME/CFS has progressed. Together, these new developments may justify renewed interest in circadian rhythm research in ME/CFS. Presently, we review ME/CFS from the perspective of circadian rhythms, covering both older and newer studies that make use of modern molecular methods. We focus on transforming growth factor beta (TGFB), a cytokine that has been previously associated with ME/CFS and has an important role in circadian rhythms, especially in peripheral cells. We propose that disrupted TGFB signaling in ME/CFS may play a role in disrupting physiological rhythms in sleep, activity, and cognition, leading to the insomnia, energy disturbances, cognition problems, depression, and autonomic dysfunction associated with ME/CFS. Since SARS-like coronavirus infections cause persistent changes in TGFB and previous coronavirus outbreaks have caused ME/CFS-like syndromes, chronobiological considerations may have immediate implications for understanding ME/CFS in the context of the COVID-19 pandemic and possibly suggest new avenues for therapeutic interventions.}, } @article {pmid35464506, year = {2022}, author = {Guerrero, M and Castroman, P and Quiroga, O and Berenguel Cook, M and Narvaez Tamayo, MA and Venturoni, L and Pergolizzi, J and Rekatsina, M and Varrassi, G}, title = {Pain Management and COVID-19: A Latin American Perspective.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23100}, pmid = {35464506}, issn = {2168-8184}, abstract = {Vaccinations and therapeutics have been developed for COVID-19, but vaccine uptake varies markedly among countries. Public health responses have also varied, in particular, with lockdown efforts and school closing. All over the world, the pandemic exposed healthcare and economic weaknesses. COVID-19 exacerbated mental health issues by exposing the population to prolonged periods of fear, anxiety, financial stress, psychological uncertainties, and sometimes isolation from even family and friends. Chronic pain patients have been disproportionately affected. The pandemic-associated stresses may have exacerbated their already painful symptoms while at the same time interrupting their access to care. The ramifications of the COVID-19 post-viral syndrome ("long COVID-19") are not yet known. COVID-19 viral infection has been associated with neuropathic pain symptoms. Tele-triage and telehealth applications can help manage chronic pain patients in the COVID-19 era, but many interventional procedures, injections, or other treatments have been delayed. The role of palliative care for patients with terminal cases of infection must be re-examined. Palliative care is a relatively new medical specialty and allows terminally ill patients to die in as much comfort and peace as can be afforded to them. More training in palliative care for all clinicians is urgently needed. COVID-19 exposed much that is wrong or weak or inadequate in our healthcare systems, but it also allowed us to embrace new technologies and develop better systems to manage the challenge of a pandemic.}, } @article {pmid35464473, year = {2022}, author = {Xiang, M and Jing, H and Wang, C and Novakovic, VA and Shi, J}, title = {Persistent Lung Injury and Prothrombotic State in Long COVID.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {862522}, pmid = {35464473}, issn = {1664-3224}, mesh = {Aftercare ; *COVID-19/complications ; Humans ; *Lung Injury/etiology ; Patient Discharge ; SARS-CoV-2 ; *Thrombophilia/etiology ; *Thrombosis/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient's lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.}, } @article {pmid35464004, year = {2022}, author = {De Lorenzo, R and Palmisano, A and Esposito, A and Gnasso, C and Nicoletti, V and Leone, R and Vignale, D and Falbo, E and Ferrante, M and Cilla, M and Magnaghi, C and Martinenghi, S and Vitali, G and Molfino, A and Rovere-Querini, P and Muscaritoli, M and Conte, C}, title = {Myosteatosis Significantly Predicts Persistent Dyspnea and Mobility Problems in COVID-19 Survivors.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {846901}, pmid = {35464004}, issn = {2296-861X}, abstract = {BACKGROUND: Persistent symptoms including dyspnea and functional impairment are common in COVID-19 survivors. Poor muscle quality (myosteatosis) associates with poor short-term outcomes in COVID-19 patients. The aim of this observational study was to assess the relationship between myosteatosis diagnosed during acute COVID-19 and patient-reported outcomes at 6 months after discharge.

METHODS: Myosteatosis was diagnosed based on CT-derived skeletal muscle radiation attenuation (SM-RA) measured during hospitalization in 97 COVID-19 survivors who had available anthropometric and clinical data upon admission and at the 6-month follow-up after discharge. Dyspnea in daily activities was assessed using the modified Medical Research Council (mMRC) scale for dyspnea. Health-related quality of life was measured using the European quality of life questionnaire three-level version (EQ-5D-3L).

RESULTS: Characteristics of patients with (lowest sex- and age-specific tertile of SM-RA) or without myosteatosis during acute COVID-19 were similar. At 6 months, patients with myosteatosis had greater rates of obesity (48.4 vs. 27.7%, p = 0.046), abdominal obesity (80.0 vs. 47.6%, p = 0.003), dyspnea (32.3 vs. 12.5%, p = 0.021) and mobility problems (32.3 vs. 12.5%, p = 0.004). Myosteatosis diagnosed during acute COVID-19 was the only significant predictor of persistent dyspnea (OR 3.19 [95% C.I. 1.04; 9.87], p = 0.043) and mobility problems (OR 3.70 [95% C.I. 1.25; 10.95], p = 0.018) at 6 months at logistic regression adjusted for sex, age, and BMI.

CONCLUSION: Myosteatosis diagnosed during acute COVID-19 significantly predicts persistent dyspnea and mobility problems at 6 months after hospital discharge independent of age, sex, and body mass.

CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [NCT04318366].}, } @article {pmid35463893, year = {2022}, author = {Buonsenso, D and Valentini, P and Macchi, M and Folino, F and Pensabene, C and Patria, MF and Agostoni, C and Castaldi, S and Lecce, M and Giannì, ML and Marchisio, P and Milani, GP and , }, title = {Caregivers' Attitudes Toward COVID-19 Vaccination in Children and Adolescents With a History of SARS-CoV-2 Infection.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {867968}, pmid = {35463893}, issn = {2296-2360}, abstract = {BACKGROUND: Limited data are available on the attitudes of caregivers toward COVID-19 vaccination in children and adolescents with a history of SARS-CoV-2 infection or Long Covid symptoms. The aim of this study was to investigate the vaccine hesitancy among caregivers of children and adolescents with a documented history of SARS-CoV-2 infection and to explore the possible associations between COVID-19 manifestations and the acceptance of the vaccine.

METHODS: Caregivers of children or adolescents with a microbiologically confirmed diagnosis of SARS-CoV-2 infection evaluated in two University Hospitals were interviewed.

RESULTS: We were able to contact 132 caregivers and 9 declined to participate. 68 caregivers (56%) were in favor of COVID-19 vaccination for their child. In the multiple logistic regression, child's age (OR 1.17, 95%CI 1.06-1.28) and hospitalization due to COVID-19 (OR 3.25, 95%CI 1.06-9.95) were positively associated with being in favor of COVID-19 vaccination. On the contrary, the occurrence of child's Long Covid was associated with a higher likelihood of being against the vaccination (OR 0.28, 95%CI 0.10-0.80).

CONCLUSIONS: This preliminary study shows that only about half of the interviewed parents of children and adolescents with a previous SARS-CoV-2 infection are willing to vaccinate them to prevent a repeated COVID-19 infection. These findings might help healthcare workers to provide tailored information to caregivers of children with a previous SARS-CoV-2 infection.}, } @article {pmid35463767, year = {2022}, author = {Borlotti, A and Thomaides-Brears, H and Georgiopoulos, G and Banerjee, R and Robson, MD and Fusco, DN and Masci, PG}, title = {The Additive Value of Cardiovascular Magnetic Resonance in Convalescent COVID-19 Patients.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {854750}, pmid = {35463767}, issn = {2297-055X}, abstract = {In COVID-19 the development of severe viral pneumonia that is coupled with systemic inflammatory response triggers multi-organ failure and is of major concern. Cardiac involvement occurs in nearly 60% of patients with pre-existing cardiovascular conditions and heralds worse clinical outcome. Diagnoses carried out in the acute phase of COVID-19 rely upon increased levels of circulating cardiac injury biomarkers and transthoracic echocardiography. These diagnostics, however, were unable to pinpoint the mechanisms of cardiac injury in COVID-19 patients. Identifying the main features of cardiac injury remains an urgent yet unmet need in cardiology, given the potential clinical consequences. Cardiovascular magnetic resonance (CMR) provides an unparalleled opportunity to gain a deeper insight into myocardial injury given its unique ability to interrogate the properties of myocardial tissue. This endeavor is particularly important in convalescent COVID-19 patients as many continue to experience chest pain, palpitations, dyspnea and exertional fatigue, six or more months after the acute illness. This review will provide a critical appraisal of research on cardiovascular damage in convalescent adult COVID-19 patients with an emphasis on the use of CMR and its value to our understanding of organ damage.}, } @article {pmid35462637, year = {2022}, author = {Saha, SA and Russo, AM and Chung, MK and Deering, TF and Lakkireddy, D and Gopinathannair, R}, title = {COVID-19 and Cardiac Arrhythmias: a Contemporary Review.}, journal = {Current treatment options in cardiovascular medicine}, volume = {24}, number = {6}, pages = {87-107}, pmid = {35462637}, issn = {1092-8464}, support = {R01 HL111314/HL/NHLBI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions.

RECENT FINDINGS: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death.

SUMMARY: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.}, } @article {pmid35460319, year = {2022}, author = {Rakusa, M and Öztürk, S and Moro, E and Helbok, R and Bassetti, CL and Beghi, E and Bereczki, D and Bodini, B and Di Liberto, G and Jenkins, TM and Macerollo, A and Maia, LF and Martinelli-Boneschi, F and Pisani, A and Priori, A and Sauerbier, A and Soffietti, R and Taba, P and von Oertzen, TJ and Zedde, M and Crean, M and Burlica, A and Cavallieri, F and Sellner, J and , }, title = {COVID-19 vaccination hesitancy among people with chronic neurological disorders: A position paper.}, journal = {European journal of neurology}, volume = {29}, number = {8}, pages = {2163-2172}, pmid = {35460319}, issn = {1468-1331}, mesh = {*COVID-19/complications/prevention & control ; *COVID-19 Vaccines/administration & dosage ; Humans ; *Nervous System Diseases ; Pandemics ; SARS-CoV-2 ; Vaccination/psychology ; *Vaccination Hesitancy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course.

METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation.

RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction.

CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.}, } @article {pmid35458189, year = {2022}, author = {Barrea, L and Verde, L and Grant, WB and Frias-Toral, E and Sarno, G and Vetrani, C and Ceriani, F and Garcia-Velasquez, E and Contreras-Briceño, J and Savastano, S and Colao, A and Muscogiuri, G}, title = {Vitamin D: A Role Also in Long COVID-19?.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458189}, issn = {2072-6643}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Vitamin D/pharmacology/therapeutic use ; *Vitamin D Deficiency/complications/epidemiology ; Vitamins/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as "long COVID-19". Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic.}, } @article {pmid35457093, year = {2022}, author = {Mohamed, MS and Johansson, A and Jonsson, J and Schiöth, HB}, title = {Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35457093}, issn = {1422-0067}, mesh = {*COVID-19/complications ; Gliosis ; Humans ; Quality of Life ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed "post-COVID-19 syndrome" or "long COVID". Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments. Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.}, } @article {pmid35456998, year = {2022}, author = {Perła-Kaján, J and Jakubowski, H}, title = {COVID-19 and One-Carbon Metabolism.}, journal = {International journal of molecular sciences}, volume = {23}, number = {8}, pages = {}, pmid = {35456998}, issn = {1422-0067}, support = {2018/29/B/NZ4/00771//National Science Center/ ; 2019/33/B/NZ4/01760//National Science Center/ ; }, mesh = {*COVID-19/complications ; Carbon/metabolism ; Folic Acid/metabolism ; Homocysteine ; Humans ; Methionine/metabolism ; SARS-CoV-2 ; Vitamin B 12/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Dysregulation of one-carbon metabolism affects a wide range of biological processes and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Accumulating evidence suggests that one-carbon metabolism plays an important role in COVID-19. The symptoms of long COVID-19 are similar to those presented by subjects suffering from vitamin B12 deficiency (pernicious anemia). The metabolism of a cell infected by the SARS-CoV-2 virus is reshaped to fulfill the need for massive viral RNA synthesis, which requires de novo purine biosynthesis involving folate and one-carbon metabolism. Many aspects of host sulfur amino acid metabolism, particularly glutathione metabolism underlying antioxidant defenses, are also taken over by the SARS-CoV-2 virus. The purpose of this review is to summarize recent findings related to one-carbon metabolism and sulfur metabolites in COVID-19 and discuss how they inform strategies to combat the disease.}, } @article {pmid35456321, year = {2022}, author = {Cattadori, G and Di Marco, S and Baravelli, M and Picozzi, A and Ambrosio, G}, title = {Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology.}, journal = {Journal of clinical medicine}, volume = {11}, number = {8}, pages = {}, pmid = {35456321}, issn = {2077-0383}, abstract = {The battle against COVID-19 has entered a new phase with Rehabilitation Centres being among the major players, because the medical outcome of COVID-19 patients does not end with the control of pulmonary inflammation marked by a negative virology test, as many patients continue to suffer from long-COVID-19 syndrome. Exercise training is known to be highly valuable in patients with cardiac or lung disease, and it exerts beneficial effects on the immune system and inflammation. We therefore reviewed past and recent papers about exercise training, considering the multifactorial features characterizing post-COVID-19 patients' clinical conditions. Consequently, we conceived a proposal for a post-COVID-19 patient exercise protocol as a combination of multiple recommended exercise training regimens. Specifically, we built pre-evaluation and exercise training for post-COVID-19 patients taking advantage of the various programs of exercise already validated for diseases that may share pathophysiological and clinical characteristics with long-COVID-19.}, } @article {pmid35456065, year = {2022}, author = {Hamdy, A and Leonardi, A}, title = {Superantigens and SARS-CoV-2.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35456065}, issn = {2076-0817}, abstract = {It has been posited SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 causes many of the biological and clinical consequences of a superantigen, and, in the context of reinfection and waning immunity, it is important to better understand the impact of a widely circulating, airborne pathogen that may be a superantigen, superantigen-like or trigger a superantigenic host response. Urgent research is needed to better understand the long-term risks being taken by governments whose policies enable widespread transmission of a potential superantigenic pathogen, and to more clearly define the vaccination and public health policies needed to protect against the consequences of repeat exposure to the pathogen.}, } @article {pmid35455789, year = {2022}, author = {Vagheggini, G and Marzetti, F and Miniati, M and Bernardeschi, L and Miccoli, M and Boni Brivio, G and Meini, S and Panait, E and Cini, E and Gemignani, A}, title = {Pulmonary Function and Psychological Burden Three Months after COVID-19: Proposal of a Comprehensive Multidimensional Assessment Protocol.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {4}, pages = {}, pmid = {35455789}, issn = {2227-9032}, abstract = {Persisting limitations in respiratory function and gas exchange, cognitive impairment, and mental health deterioration have been observed weeks and months after acute SARS-CoV-2 (COVID-19). The present study aims at assessing the impairment at three-months in patients who successfully recovered from acute COVID-19. We collected data from May to July 2020. Patients underwent a multidimensional extensive assessment including pulmonary function test, psychological tests, thoracic echo scan, and functional exercise capacity. A total of 21 patients (M:13; Age 57.05 ± 11.02) completed the global assessment. A considerable proportion of patients showed symptoms of post-traumatic stress disorder (28.6%), moderate depressive symptoms (9.5%), and clinical insomnia (9.5%); 14.3% of patients exhibited moderate anxiety. A total of eleven patients (52.4%) showed impaired respiratory gas exchange capacity (P-DLCO, DLCO ≤ 79% pred). Compared to patients with normal gas exchange, the P-DLCO subgroup perceived a significant worsening in quality of life (QoL) after COVID-19 (p = 0.024), higher fatigue (p = 0.005), and higher impact of lung disease (p = 0.013). In P-DLCO subgroup, higher echo score was positively associated with hospitalization length of stay (p = 0.047), depressive symptoms (p = 0.042), fatigue (p = 0.035), impairment in mental health (p = 0.035), and impact of lung disease in health status (p = 0.020). Pulmonary function and echo scan lung changes were associated to worsened QoL, fatigue, and psychological distress symptoms.}, } @article {pmid35455008, year = {2022}, author = {Boaventura, P and Macedo, S and Ribeiro, F and Jaconiano, S and Soares, P}, title = {Post-COVID-19 Condition: Where Are We Now?.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {35455008}, issn = {2075-1729}, abstract = {COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.}, } @article {pmid35454374, year = {2022}, author = {Soejima, Y and Otsuka, Y and Tokumasu, K and Nakano, Y and Harada, K and Nakamoto, K and Sunada, N and Sakurada, Y and Hasegawa, K and Hagiya, H and Ueda, K and Otsuka, F}, title = {Late-Onset Hypogonadism in a Male Patient with Long COVID Diagnosed by Exclusion of ME/CFS.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {4}, pages = {}, pmid = {35454374}, issn = {1648-9144}, mesh = {Adult ; *COVID-19/complications ; Fatigue/etiology ; *Fatigue Syndrome, Chronic ; Gonadotropin-Releasing Hormone ; Humans ; *Hypogonadism/complications/diagnosis ; Luteinizing Hormone ; Male ; SARS-CoV-2 ; Testosterone/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).}, } @article {pmid35454144, year = {2022}, author = {Piazza, M and Di Cicco, M and Pecoraro, L and Ghezzi, M and Peroni, D and Comberiati, P}, title = {Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome.}, journal = {Biomolecules}, volume = {12}, number = {4}, pages = {}, pmid = {35454144}, issn = {2218-273X}, mesh = {*COVID-19/complications ; Child ; Humans ; Inflammation ; SARS-CoV-2 ; Vitamins ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences.}, } @article {pmid35453505, year = {2022}, author = {Margaria, JP and Moretta, L and Alves-Filho, JC and Hirsch, E}, title = {PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury.}, journal = {Biomedicines}, volume = {10}, number = {4}, pages = {}, pmid = {35453505}, issn = {2227-9059}, abstract = {Pulmonary fibrosis is a pathological fibrotic process affecting the lungs of five million people worldwide. The incidence rate will increase even more in the next years due to the long-COVID-19 syndrome, but a resolving treatment is not available yet and usually prognosis is poor. The emerging role of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling in fibrotic processes has inspired the testing of drugs targeting the PI3K/Akt pathway that are currently under clinical evaluation. This review highlights the progress in understanding the role of PI3K/Akt in the development of lung fibrosis and its causative pathological context, including sepsis as well as acute lung injury (ALI) and its consequent acute respiratory distress syndrome (ARDS). We further summarize current knowledge about PI3K inhibitors for pulmonary fibrosis treatment, including drugs under development as well as in clinical trials. We finally discuss how the design of inhaled compounds targeting the PI3K pathways might potentiate efficacy and improve tolerability.}, } @article {pmid35452519, year = {2022}, author = {Gaylis, NB and Ritter, A and Kelly, SA and Pourhassan, NZ and Tiwary, M and Sacha, JB and Hansen, SG and Recknor, C and Yang, OO}, title = {Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {7}, pages = {1232-1234}, pmid = {35452519}, issn = {1537-6591}, mesh = {*COVID-19 ; Chemokines, CC ; Humans ; Immunosuppression Therapy ; Receptors, CCR5 ; }, abstract = {In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.}, } @article {pmid35452027, year = {2023}, author = {Hastie, CE and Foster, HME and Jani, BD and O'Donnell, CA and Ho, FK and Pell, JP and Sattar, N and Katikireddi, SV and Mair, FS and Nicholl, BI}, title = {Chronic pain and COVID-19 hospitalisation and mortality: a UK Biobank cohort study.}, journal = {Pain}, volume = {164}, number = {1}, pages = {84-90}, pmid = {35452027}, issn = {1872-6623}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_UU_00022/2/MRC_/Medical Research Council/United Kingdom ; SCAF/15/02/CSO_/Chief Scientist Office/United Kingdom ; MR/T001585/1/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *COVID-19 ; Cohort Studies ; *Chronic Pain/epidemiology ; Post-Acute COVID-19 Syndrome ; Biological Specimen Banks ; Hospitalization ; United Kingdom/epidemiology ; }, abstract = {The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P -value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P -value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.}, } @article {pmid35451721, year = {2023}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Florencio, LL and Navarro-Pardo, E and Rodríguez-Jiménez, J and Torres-Macho, J and Pellicer-Valero, OJ}, title = {Clustering analysis reveals different profiles associating long-term post-COVID symptoms, COVID-19 symptoms at hospital admission and previous medical co-morbidities in previously hospitalized COVID-19 survivors.}, journal = {Infection}, volume = {51}, number = {1}, pages = {61-69}, pmid = {35451721}, issn = {1439-0973}, support = {LONG-COVID-EXP-CM//Comunidad de Madrid/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; Hospitalization ; Post-Acute COVID-19 Syndrome ; Cluster Analysis ; Hospitals ; Survivors ; Morbidity ; }, abstract = {PURPOSE: To identify subgroups of COVID-19 survivors exhibiting long-term post-COVID symptoms according to clinical/hospitalization data by using cluster analysis in order to foresee the illness progress and facilitate subsequent prognosis.

METHODS: Age, gender, height, weight, pre-existing medical comorbidities, Internal Care Unit (ICU) admission, days at hospital, and presence of COVID-19 symptoms at hospital admission were collected from hospital records in a sample of patients recovered from COVID-19 at five hospitals in Madrid (Spain). A predefined list of post-COVID symptoms was systematically assessed a mean of 8.4 months (SD 15.5) after hospital discharge. Anxiety/depressive levels and sleep quality were assessed with the Hospital Anxiety and Depression Scale and Pittsburgh Sleep Quality Index, respectively. Cluster analysis was used to identify groupings of COVID-19 patients without introducing any previous assumptions, yielding three different clusters associating post-COVID symptoms with acute COVID-19 symptoms at hospital admission.

RESULTS: Cluster 2 grouped subjects with lower prevalence of medical co-morbidities, lower number of COVID-19 symptoms at hospital admission, lower number of post-COVID symptoms, and almost no limitations with daily living activities when compared to the others. In contrast, individuals in cluster 0 and 1 exhibited higher number of pre-existing medical co-morbidities, higher number of COVID-19 symptoms at hospital admission, higher number of long-term post-COVID symptoms (particularly fatigue, dyspnea and pain), more limitations on daily living activities, higher anxiety and depressive levels, and worse sleep quality than those in cluster 2.

CONCLUSIONS: The identified subgrouping may reflect different mechanisms which should be considered in therapeutic interventions.}, } @article {pmid35451276, year = {2022}, author = {Perrin, A and Caflisch, M}, title = {[A new challenge: post-COVID syndrome in teenagers].}, journal = {Revue medicale suisse}, volume = {18}, number = {778}, pages = {737-740}, doi = {10.53738/REVMED.2022.18.778.737}, pmid = {35451276}, issn = {1660-9379}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Humans ; Quality of Life ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID syndrome (or long COVID) is a set of persistent symptoms occurring after a documented SARS-CoV-2 infection. Children and adolescents are also affected, with similar symptoms than adults. To date there is no clinical or biological parameter allowing to confirm the diagnosis, which relies on the presence of typical symptoms associated with a suggestive temporality, in the absence of any other explanation. These persistent symptoms can have a strong impact on the quality of life and schooling. In our specialized consultation for pediatric post-COVID syndrome, we offer a global and multidisciplinary follow-up to patients and their families, supporting them progressively resuming physical and mental activity, and pursuing school attendance to avoid dropout.}, } @article {pmid35450781, year = {2022}, author = {Mayfield, HJ and Lau, CL and Sinclair, JE and Brown, SJ and Baird, A and Litt, J and Vuorinen, A and Short, KR and Waller, M and Mengersen, K}, title = {Designing an evidence-based Bayesian network for estimating the risk versus benefits of AstraZeneca COVID-19 vaccine.}, journal = {Vaccine}, volume = {40}, number = {22}, pages = {3072-3084}, pmid = {35450781}, issn = {1873-2518}, mesh = {Bayes Theorem ; *COVID-19/complications/prevention & control ; COVID-19 Vaccines/adverse effects ; ChAdOx1 nCoV-19 ; Humans ; *Thrombocytopenia ; Post-Acute COVID-19 Syndrome ; }, abstract = {Uncertainty surrounding the risk of developing and dying from Thrombosis and Thrombocytopenia Syndrome (TTS) associated with the AstraZeneca (AZ) COVID-19 vaccine may contribute to vaccine hesitancy. A model is urgently needed to combine and effectively communicate evidence on the risks versus benefits of the AZ vaccine. We developed a Bayesian network to consolidate evidence on risks and benefits of the AZ vaccine, and parameterised the model using data from a range of empirical studies, government reports, and expert advisory groups. Expert judgement was used to interpret the available evidence and determine the model structure, relevant variables, data for inclusion, and how these data were used to inform the model. The model can be used as a decision-support tool to generate scenarios based on age, sex, virus variant and community transmission rates, making it useful for individuals, clinicians, and researchers to assess the chances of different health outcomes. Model outputs include the risk of dying from TTS following the AZ COVID-19 vaccine, the risk of dying from COVID-19 or COVID-19-associated atypical severe blood clots under different scenarios. Although the model is focused on Australia, it can be adapted to international settings by re-parameterising it with local data. This paper provides detailed description of the model-building methodology, which can be used to expand the scope of the model to include other COVID-19 vaccines, booster doses, comorbidities and other health outcomes (e.g., long COVID) to ensure the model remains relevant in the face of constantly changing discussion on risks versus benefits of COVID-19 vaccination.}, } @article {pmid35450524, year = {2022}, author = {Stefano, GB and Kream, RM}, title = {Viruses Broaden the Definition of Life by Genomic Incorporation of Artificial Intelligence and Machine Learning Processes.}, journal = {Current neuropharmacology}, volume = {20}, number = {10}, pages = {1888-1893}, pmid = {35450524}, issn = {1875-6190}, mesh = {Artificial Intelligence ; *COVID-19/complications ; Genomics ; Humans ; Machine Learning ; SARS-CoV-2/genetics ; *Viruses ; Post-Acute COVID-19 Syndrome ; }, abstract = {Viruses have been classified as non-living because they require a cellular host to support their replicative processes. Empirical investigations have significantly advanced our understanding of the many strategies employed by viruses to usurp and divert host regulatory and metabolic processes to drive the synthesis and release of infectious particles. The recent emergence of SARS-CoV-2 has permitted us to evaluate and discuss a potentially novel classification of viruses as living entities. The ability of SARS CoV-2 to engender comprehensive regulatory control of integrative cellular processes is strongly suggestive of an inherently dynamic informational registry that is programmatically encoded by linear ssRNA sequences responding to distinct evolutionary constraints. Responses to positive evolutionary constraints have resulted in a single-stranded RNA viral genome that occupies a threedimensional space defined by conserved base-paring resulting from a complex pattern of both secondary and tertiary structures. Additionally, regulatory control of virus-mediated infectious processes relies on extensive protein-protein interactions that drive conformational matching and shape recognition events to provide a functional link between complementary viral and host nucleic acid and protein domains. We also recognize that the seamless integration of complex replicative processes is highly dependent on the precise temporal matching of complementary nucleotide sequences and their corresponding structural and non-structural viral proteins. Interestingly, the deployment of concerted transcriptional and translational activities within targeted cellular domains may be modeled by artificial intelligence (AI) strategies that are inherently fluid, self-correcting, and adaptive at accommodating temporal changes in host defense mechanisms. An in-depth understanding of multiple self-correcting AIassociated viral processes will most certainly lead to novel therapeutic development platforms, notably the design of efficacious neuropharmacological agents to treat chronic CNS syndromes associated with long-COVID. In summary, it appears that viruses, notably SARS-CoV-2, are very much alive due to acquired genetic advantages that are intimately entrained to existential host processes via evolutionarily constrained AI-associated learning paradigms.}, } @article {pmid35449732, year = {2022}, author = {Wang, C and Yu, C and Jing, H and Wu, X and Novakovic, VA and Xie, R and Shi, J}, title = {Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {861703}, pmid = {35449732}, issn = {2235-2988}, mesh = {Anticoagulants/therapeutic use ; *COVID-19/complications ; Humans ; Hypoxia ; Inflammation/complications ; Quality of Life ; SARS-CoV-2 ; *Thrombosis/etiology/prevention & control ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.}, } @article {pmid35449467, year = {2022}, author = {Olschewski, H and Eber, E and Bucher, B and Hackner, K and Handzhiev, S and Hoetzenecker, K and Idzko, M and Klepetko, W and Kovacs, G and Lamprecht, B and Löffler-Ragg, J and Meilinger, M and Müller, A and Prior, C and Schindler, O and Täubl, H and Zacharasiewicz, A and Zwick, RH and Arns, BM and Bolitschek, J and Cima, K and Gingrich, E and Hochmair, M and Horak, F and Jaksch, P and Kropfmüller, R and Pfleger, A and Puchner, B and Puelacher, C and Rodriguez, P and Salzer, HJF and Schenk, P and Stelzmüller, I and Strenger, V and Urban, M and Wagner, M and Wimberger, F and Flick, H}, title = {Management of patients with SARS-CoV-2 infections with focus on patients with chronic lung diseases (as of 10 January 2022) : Updated statement of the Austrian Society of Pneumology (ASP).}, journal = {Wiener klinische Wochenschrift}, volume = {134}, number = {9-10}, pages = {399-419}, pmid = {35449467}, issn = {1613-7671}, mesh = {Austria/epidemiology ; *COVID-19/epidemiology ; Child ; Communicable Disease Control ; Humans ; *Lung Diseases/epidemiology/therapy ; *Pulmonary Medicine ; SARS-CoV-2 ; Young Adult ; }, abstract = {The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV‑2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV‑2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV‑2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.}, } @article {pmid35447962, year = {2022}, author = {Frosolini, A and Parrino, D and Fabbris, C and Fantin, F and Inches, I and Invitto, S and Spinato, G and Filippis, C}, title = {Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series.}, journal = {Brain sciences}, volume = {12}, number = {4}, pages = {}, pmid = {35447962}, issn = {2076-3425}, abstract = {An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction. A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin' Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs. The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis.}, } @article {pmid35447302, year = {2022}, author = {Taquet, M and Dercon, Q and Harrison, PJ}, title = {Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections.}, journal = {Brain, behavior, and immunity}, volume = {103}, number = {}, pages = {154-162}, pmid = {35447302}, issn = {1090-2139}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; Disease Progression ; Humans ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021, i.e. before the emergence of the Omicron variant). Associations with the number of vaccine doses (1 vs. 2) and age (<60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p < 0.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those <60 years-old, whereas no robust associations were observed in those ≥60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.}, } @article {pmid35444473, year = {2022}, author = {Medina-Perucha, L and López-Jiménez, T and Holst, AS and Jacques-Aviñó, C and Munrós-Feliu, J and Martínez-Bueno, C and Valls-Llobet, C and Pinzón-Sanabria, D and Vicente-Hernández, MM and Berenguera, A}, title = {Self-Reported Menstrual Alterations During the COVID-19 Syndemic in Spain: A Cross-Sectional Study.}, journal = {International journal of women's health}, volume = {14}, number = {}, pages = {529-544}, pmid = {35444473}, issn = {1179-1411}, abstract = {INTRODUCTION: Available evidence suggests that there might be an association between the stressors experienced during the COVID-19 syndemic and changes in menstrual patterns. The aim of this study was to assess self-reported menstrual alterations during the COVID-19 syndemic among women and people who menstruate aged 18-55 in Spain.

MATERIALS AND METHODS: A cross-sectional online survey-based study was conducted (March-July 2021). Descriptive statistics were calculated and multivariate logistic regression models were constructed. This study was conducted as part of the "Equity and Menstrual Health in Spain" research project.

RESULTS: Among participants (N=17,455), 39.4% reported menstrual alterations since the start of the syndemic. Participants self-reporting long COVID-19 presented higher odds of menstrual alterations (aOR: 1.34, 95% CI, 1.15-1.57). In participants with no history of COVID-19, the risk for self-reported menstrual alterations was significantly higher based on employment situation, among participants experiencing financial issues (eg, financial issues always/many times <12 months: aOR: 1.68, 95% CI, 1.48-1.90), poorer self-perceived health (eg, poor: aOR: 2.00, 95% CI, 1.31-3.07), and those diagnosed with polycystic ovary syndrome (aOR: 1.13, 95% CI, 1.02-1.26). Among participants with a self-reported COVID-19 diagnosis, factors that significantly increased the odds for menstrual alterations were experiencing financial strains (eg, financial issues always/many times <12 months: aOR: 1.53, 95% CI, 1.09-2.14), poorer self-perceived health (eg, poor: aOR: 3.09, 95% CI, 1.01-9.52). Overall, factors that decreased the odds of reporting menstrual alterations included age >25, being a carer, not having a gynecological condition and using hormonal contraception.

DISCUSSION AND CONCLUSIONS: Findings suggest an impact of the COVID-19 syndemic on menstrual patterns. Social inequities in reporting menstrual alterations were identified. While the risk of reporting menstrual alterations was higher among participants with long COVID-19, evidence is not conclusive. Further research on menstrual health in the context of COVID-19 is needed, also to inform policy and practice.}, } @article {pmid35443975, year = {2022}, author = {Lin, Y and Saper, R and Patil, SJ}, title = {Long COVID Shared Medical Appointments: Lifestyle and Mind-Body Medicine With Peer Support.}, journal = {Annals of family medicine}, volume = {20}, number = {4}, pages = {383}, doi = {10.1370/afm.2817}, pmid = {35443975}, issn = {1544-1717}, mesh = {Appointments and Schedules ; *COVID-19/complications ; Humans ; Life Style ; Mind-Body Therapies ; *Shared Medical Appointments ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35441168, year = {2022}, author = {Victor, J and Jordan, T and Lamkin, E and Ikeh, K and March, A and Frere, J and Crompton, A and Allen, L and Fanning, J and Lim, WY and Muoio, D and Fouquerel, E and Martindale, R and Dewitt, J and deLance, N and Taatjes, D and Dragon, J and Holcombe, R and Greenblatt, M and Kaminsky, D and Hong, J and Zhou, P and tenOever, B and Chatterjee, N}, title = {SARS-CoV-2 hijacks host cell genome instability pathways.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35441168}, issn = {2693-5015}, support = {P20 GM103449/GM/NIGMS NIH HHS/United States ; P30 GM103498/GM/NIGMS NIH HHS/United States ; R21 CA191448/CA/NCI NIH HHS/United States ; S10 OD025030/OD/NIH HHS/United States ; R35 GM142982/GM/NIGMS NIH HHS/United States ; R00 ES027028/ES/NIEHS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; P30 RR032135/RR/NCRR NIH HHS/United States ; }, abstract = {The repertoire of coronavirus disease 2019 (COVID-19)-mediated adverse health outcomes has continued to expand in infected patients, including the susceptibility to developing long-COVID; however, the molecular underpinnings at the cellular level are poorly defined. In this study, we report that SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection triggers host cell genome instability by modulating the expression of molecules of DNA repair and mutagenic translesion synthesis. Further, SARS-CoV-2 infection causes genetic alterations, such as increased mutagenesis, telomere dysregulation, and elevated microsatellite instability (MSI). The MSI phenotype was coupled to reduced MLH1, MSH6, and MSH2 in infected cells. Strikingly, pre-treatment of cells with the REV1-targeting translesion DNA synthesis inhibitor, JH-RE-06, suppresses SARS-CoV-2 proliferation and dramatically represses the SARS-CoV-2-dependent genome instability. Mechanistically, JH-RE-06 treatment induces autophagy, which we hypothesize limits SARS-CoV-2 proliferation and, therefore, the hijacking of host-cell genome instability pathways. These results have implications for understanding the pathobiological consequences of COVID-19.}, } @article {pmid35441129, year = {2022}, author = {Heald, A and Perrin, R and Walther, A and Stedman, M and Hann, M and Mukherjee, A and Riste, L}, title = {Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention.}, journal = {Cardiovascular endocrinology & metabolism}, volume = {11}, number = {2}, pages = {e0261}, pmid = {35441129}, issn = {2574-0954}, abstract = {UNLABELLED: In the early days of the first global wave of the COVID-19 pandemic, the potential for a postviral syndrome to manifest following COVID-19 infection was first recognized. Here, we present an analysis of a case series of the first 20 patients' data collected in clinical practice to evaluate the potential of a possible alternative treatment for Long COVID.

METHODS: Face-to-face treatment sessions with Perrin technique practitioners occurred weekly involving effleurage/other manual articulatory techniques. The individuals being treated also undertook daily self-massage along with gentle mobility exercises. Patients recorded symptom severity using the self-report 54-item profile of fatigue-related states (PFRS) before and after treatment.

RESULTS: The mean age of male patients was 41.8 years (range, 29-53 years), and for female patients, 39.3 years (range, 28-50 years). None of the participants had a prior diagnosis of chronic fatigue syndrome, and all were new attendees to the clinics at the time of initial assessment. The average number of treatment sessions was 9.7 in men and 9.4 in women. The reduction in PFRS scores was 45% in men and 52% in women. The highest subscale scores on average were for fatigue, with the lowest for somatic symptoms. All subscale scores showed, on average, a similar reduction of approximately 50% postintervention, with the reduction in score relating to a decrease in the severity of symptoms.

CONCLUSION: Our findings suggest that a specific manual lymphatic drainage intervention may help to reduce fatigue symptoms related to Long COVID. Perhaps preventing acute symptoms through early intervention.}, } @article {pmid35440166, year = {2022}, author = {Kaye, DM and Vizi, D and Graham, S and Wang, B and Shihata, W and Nanayakkara, S and Mariani, J and Premaratne, M}, title = {Physiologic Insights Into Long COVID Breathlessness.}, journal = {Circulation. Heart failure}, volume = {15}, number = {6}, pages = {e009346}, pmid = {35440166}, issn = {1941-3297}, mesh = {*COVID-19/complications ; Dyspnea/diagnosis/etiology ; *Heart Failure ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35434687, year = {2022}, author = {Robineau, O and Wiernik, E and Lemogne, C and de Lamballerie, X and Ninove, L and Blanché, H and Deleuze, JF and Ribet, C and Kab, S and Goldberg, M and Severi, G and Touvier, M and Zins, M and Carrat, F}, title = {Persistent symptoms after the first wave of COVID-19 in relation to SARS-CoV-2 serology and experience of acute symptoms: A nested survey in a population-based cohort.}, journal = {The Lancet regional health. Europe}, volume = {17}, number = {}, pages = {100363}, pmid = {35434687}, issn = {2666-7762}, abstract = {BACKGROUND: Many patients report persistent symptoms after COVID-19. Our aim was to determine whether some of these symptoms were more associated with past SARS-CoV-2 infection compared to other conditions.

METHODS: This prospective survey was nested in CONSTANCES, a randomly selected French population-based cohort, started in 2012. All participants being followed-up by internet completed 2 questionnaires during the first wave of the pandemic focusing on the acute symptoms of their COVID-19-like illness. Serological tests for SARS-CoV-2 were then performed (May-Nov 2020). Between December 2020 and January 2021, participants completed a third questionnaire about symptoms that had lasted more than 2 months. Participants were classified into four groups according to both European Center for Diseases Control (ECDC) criteria for COVID-19 (ECDC+ or ECDC-) and serological SARS-CoV-2 test results (Sero+ or Sero-). To compare the risk of each persistent symptom among the groups, logistic regression models were adjusted for age, sex, educational level, comorbidities, and the number of acute symptoms declared during the first wave of the epidemic. A mediation analysis was performed to estimate the direct effect of the infection on persistent symptoms and its indirect effect via the initial clinical presentation.

FINDINGS: The analysis was performed in 25,910 participants. There was a higher risk of persistent dysgeusia/anosmia, dyspnea and asthenia in the ECDC+/Sero+ group than in the ECDC+/Sero- group (OR: 6.83 [4.47-10.42], 1.69 [1.07-2.6] and 1.48 [1.05-2.07], respectively). Abdominal pain, sensory symptoms or sleep disorders were at lower risk in the ECDC+/Sero+ group than in the ECDC+/Sero- group (0.51 [0.24-0.96], 0.40 [0.16-0.85], and 0.69 [0.49-0.95], respectively). The mediation analysis revealed that the association of the serological test results with each symptom was mainly mediated by ECDC symptoms (proportion mediated range 50-107%).

CONCLUSION: A greater risk of persistent dysgeusia/anosmia, dyspnea and asthenia was observed in SARS-CoV-2 infected people. The initial clinical presentation substantially drives the association of positive serological test results with persistent symptoms.

FUNDING: French National Research Agency.}, } @article {pmid35433541, year = {2022}, author = {Vizzari, G and Morniroli, D and Tiraferri, V and Castaldi, S and Patria, MF and Marchisio, P and Agostoni, C and Mosca, F and Buonsenso, D and Milani, GP and Giannì, ML and , }, title = {Modulating Role of Breastfeeding Toward Long COVID Occurrence in Children: A Preliminary Study.}, journal = {Frontiers in pediatrics}, volume = {10}, number = {}, pages = {884962}, pmid = {35433541}, issn = {2296-2360}, abstract = {The SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus-2) pandemic has forced the global health system to face new challenges both in the acute management of COVID-19 (Coronavirus Disease 2019) patients and in its consequences. In particular, the long-term effects of this new virus, especially in children, are still poorly understood. Scientific research is currently trying to understand the mechanisms underlying the so called "long COVID syndrome". Since the beginning of the pandemic, breastmilk has been studied for its antiviral and immunomodulatory properties. Based on these assumptions, we conducted a preliminary study in order to investigate the prevalence of long COVID in a cohort of Italian children with previously detected SARS-CoV-2 infection and evaluate if breastfeeding might play a role in modulating long COVID occurrence.}, } @article {pmid35431691, year = {2022}, author = {Benson, D}, title = {Conversation with Shonna Stokowski: The Gupta Brain Retraining Program for Long Covid.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {21}, number = {1}, pages = {24-27}, pmid = {35431691}, issn = {1546-993X}, } @article {pmid35431658, year = {2022}, author = {Zhu, F and Ang, JY}, title = {COVID-19 Infection in Children: Diagnosis and Management.}, journal = {Current infectious disease reports}, volume = {24}, number = {4}, pages = {51-62}, pmid = {35431658}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Due to the rapidly changing landscape of COVID-19, the purpose of this review is to provide a concise and updated summary of pediatric COVID-19 diagnosis and management.

RECENT FINDINGS: The relative proportion of pediatric cases have significantly increased following the emergence of the Omicron variant (from < 2% in the early pandemic to 25% from 1/27 to 2/3/22). While children present with milder symptoms than adults, severe disease can still occur, particularly in children with comorbidities. There is a relative paucity of pediatric data in the management of COVID-19 and the majority of recommendations remain based on adult data.

SUMMARY: Fever and cough remain the most common clinical presentations, although atypical presentations such as "COVID toes," anosmia, and croup may be present. Children are at risk for post-infectious complications such as MIS-C and long COVID. Nucleic acid amplification tests through respiratory PCR remain the mainstay of diagnosis. The mainstay of management remains supportive care and prevention through vaccination is highly recommended. In patients at increased risk of progression, interventions such as monoclonal antibody therapy, PO Paxlovid, or IV remdesivir × 3 days should be considered. In patients with severe disease, the use of remdesivir, dexamethasone, and immunomodulatory agents (tocilizumab, baricitinib) is recommended. Children can be at risk for thrombosis from COVID-19 and anticoagulation is recommended in children with markedly elevated D-dimer levels or superimposed clinical risk factors for hospital associated venous thromboembolism.}, } @article {pmid35431398, year = {2022}, author = {Gao, Y and Liang, WQ and Li, YR and He, JX and Guan, WJ}, title = {The Short- and Long-Term Clinical, Radiological and Functional Consequences of COVID-19.}, journal = {Archivos de bronconeumologia}, volume = {58}, number = {}, pages = {32-38}, pmid = {35431398}, issn = {1579-2129}, mesh = {*COVID-19 ; Forecasting ; Humans ; Lung/diagnostic imaging ; Risk Factors ; }, abstract = {As with the rapid increase of the number of patients who have recovered from COVID-19 globally, there needs to be a major shift of the focus from rapid pathogen detection, treatment and prevention to the promotion of better recovery. Notwithstanding the scarcity of our understandings, recent studies have unraveled a plethora of pulmonary and systemic consequences which require medical attention. These consequences remained as of the end of follow-up which ranged from 1 month to 1 year. Here, we review the consequences of COVID-19 in terms of the residual symptoms, radiological and functional manifestations, and identify the potential risk factors that contribute to a prolonged recovery. We also summarize the benefits of clinical interventions (particularly the pulmonary rehabilitation program), and address several undetermined concerns and key future research directions.}, } @article {pmid35429399, year = {2022}, author = {Chen, C and Haupert, SR and Zimmermann, L and Shi, X and Fritsche, LG and Mukherjee, B}, title = {Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review.}, journal = {The Journal of infectious diseases}, volume = {226}, number = {9}, pages = {1593-1607}, doi = {10.1093/infdis/jiac136}, pmid = {35429399}, issn = {1537-6613}, mesh = {Humans ; *COVID-19 ; *Pneumonia, Viral/epidemiology ; *Coronavirus Infections/epidemiology ; Pandemics ; Prevalence ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: This study aims to examine the worldwide prevalence of post-coronavirus disease 2019 (COVID-19) condition, through a systematic review and meta-analysis.

METHODS: PubMed, Embase, and iSearch were searched on July 5, 2021 with verification extending to March 13, 2022. Using a random-effects framework with DerSimonian-Laird estimator, we meta-analyzed post-COVID-19 condition prevalence at 28+ days from infection.

RESULTS: Fifty studies were included, and 41 were meta-analyzed. Global estimated pooled prevalence of post-COVID-19 condition was 0.43 (95% confidence interval [CI], .39-.46). Hospitalized and nonhospitalized patients had estimates of 0.54 (95% CI, .44-.63) and 0.34 (95% CI, .25-.46), respectively. Regional prevalence estimates were Asia (0.51; 95% CI, .37-.65), Europe (0.44; 95% CI, .32-.56), and United States of America (0.31; 95% CI, .21-.43). Global prevalence for 30, 60, 90, and 120 days after infection were estimated to be 0.37 (95% CI, .26-.49), 0.25 (95% CI, .15-.38), 0.32 (95% CI, .14-.57), and 0.49 (95% CI, .40-.59), respectively. Fatigue was the most common symptom reported with a prevalence of 0.23 (95% CI, .17-.30), followed by memory problems (0.14; 95% CI, .10-.19).

CONCLUSIONS: This study finds post-COVID-19 condition prevalence is substantial; the health effects of COVID-19 seem to be prolonged and can exert stress on the healthcare system.}, } @article {pmid35422571, year = {2022}, author = {Ripani, U and Bisaccia, M and Meccariello, L}, title = {Dexamethasone and Nutraceutical Therapy Can Reduce the Myalgia Due to COVID-19 - a Systemic Review of the Active Substances that Can Reduce the Expression of Interlukin-6.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {76}, number = {1}, pages = {66-71}, pmid = {35422571}, issn = {1986-5961}, mesh = {Humans ; *COVID-19 Drug Treatment ; Dexamethasone/therapeutic use ; Dietary Supplements ; Inflammation ; Interleukin-6 ; Myalgia/etiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Myalgia reflects generalized inflammation and cytokine response and can be the onset symptom of 36% of patients with COVID-19. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) levels in plasma and upper respiratory secretions directly correlate with the magnitude of viral replication, fever, and respiratory and systemic symptoms, including musculoskeletal clinical manifestations.

OBJECTIVE: The aim of our work is to report literature scientific investigation clinical protocol to reduce the immunomodulation and inflammatory response nutraceutical therapy associated with dexamethasone and how can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.

METHODS: We searched in Pubmed and Cochrane the nautriceutical drugs to treat the immune modulation of organism to COVID-19. We put these keywords: immune inflammation, desease descriptions, epidemiology COVID-19; immunomodulations; IL-6; Rheumatic Symptoms; Joint; Musculoskeletal Disorders; dexamethasone; Polydatin; Zinc; Melatonin; N- Acetyl Cysteine; Colostrum; L- Glutamine; Vitamin D3.

RESULTS: We found 61 papers. All the authors analyze them. After the Analyze we suggest the use of response nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.

CONCLUSION: According the scientific literature nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19.}, } @article {pmid35421963, year = {2022}, author = {Angeles, MR and Wanni Arachchige Dona, S and Nguyen, HD and Le, LK and Hensher, M}, title = {Modelling the potential acute and post-acute burden of COVID-19 under the Australian border re-opening plan.}, journal = {BMC public health}, volume = {22}, number = {1}, pages = {757}, pmid = {35421963}, issn = {1471-2458}, mesh = {Australia/epidemiology ; *COVID-19/complications/epidemiology ; Cost of Illness ; Critical Illness ; Humans ; Quality-Adjusted Life Years ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Concerns have grown that post-acute sequelae of COVID-19 may affect significant numbers of survivors. However, the analyses used to guide policy-making for Australia's national and state re-opening plans have not incorporated non-acute illness in their modelling. We, therefore, develop a model by which to estimate the potential acute and post-acute COVID-19 burden using disability-adjusted life years (DALYs) associated with the re-opening of Australian borders and the easing of other public health measures, with particular attention to longer-term, post-acute consequences and the potential impact of permanent functional impairment following COVID-19.

METHODS: A model was developed based on the European Burden of Disease Network protocol guideline and consensus model to estimate the burden of COVID-19 using DALYs. Data inputs were based on publicly available sources. COVID-19 infection and different scenarios were drawn from the Doherty Institute's modelling report to estimate the likely DALY losses under the Australian national re-opening plan. Long COVID prevalence, post-intensive care syndrome (PICS) and potential permanent functional impairment incidences were drawn from the literature. DALYs were calculated for the following health states: the symptomatic phase, Long COVID, PICS and potential permanent functional impairment (e.g., diabetes, Parkinson's disease, dementia, anxiety disorders, ischemic stroke). Uncertainty and sensitivity analysis were performed to examine the robustness of the results.

RESULTS: Mortality was responsible for 72-74% of the total base case COVID-19 burden. Long COVID and post-intensive care syndrome accounted for at least 19 and 3% of the total base case DALYs respectively. When included in the analysis, potential permanent impairment could contribute to 51-55% of total DALYs lost.

CONCLUSIONS: The impact of Long COVID and potential long-term post-COVID disabilities could contribute substantially to the COVID-19 burden in Australia's post-vaccination setting. As vaccination coverage increases, the share of COVID-19 burden driven by longer-term morbidity rises relative to mortality. As Australia re-opens, better estimates of the COVID-19 burden can assist with decision-making on pandemic control measures and planning for the healthcare needs of COVID-19 survivors. Our estimates highlight the importance of valuing the morbidity of post-COVID-19 sequelae, above and beyond simple mortality and case statistics.}, } @article {pmid35420565, year = {2022}, author = {Bonnet, U and Juckel, G}, title = {COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants-A Scoping Review.}, journal = {Journal of clinical psychopharmacology}, volume = {42}, number = {3}, pages = {284-292}, pmid = {35420565}, issn = {1533-712X}, mesh = {Antidepressive Agents/pharmacology/therapeutic use ; *COVID-19/complications ; Fluoxetine/pharmacology ; Fluvoxamine/pharmacology/therapeutic use ; Humans ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Selective Serotonin Reuptake Inhibitors/adverse effects ; *Serotonin and Noradrenaline Reuptake Inhibitors ; *Trazodone ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {PURPOSE/BACKGROUND: Studies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2-infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.

METHODS/PROCEDURES: We conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.

FINDING/RESULTS: As of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19-related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.

IMPLICATIONS/CONCLUSIONS: At present, the best evidence of an "anti-COVID-19" potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute "dark zones" in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.}, } @article {pmid35419559, year = {2022}, author = {Guckert, M and Milanovic, K and Hannig, J and Simon, D and Wettengl, T and Evers, D and Kleyer, A and Keller, T and Pitt, J}, title = {The Disruption of Trust in the Digital Transformation Leading to Health 4.0.}, journal = {Frontiers in digital health}, volume = {4}, number = {}, pages = {815573}, pmid = {35419559}, issn = {2673-253X}, abstract = {The specification and application of policies and guidelines for public health, medical education and training, and screening programmes for preventative medicine are all predicated on trust relationships between medical authorities, health practitioners and patients. These relationships are in turn predicated on a verbal contract that is over two thousand years old. The impact of information and communication technology (ICT), underpinning Health 4.0, has the potential to disrupt this analog relationship in several dimensions; but it also presents an opportunity to strengthen it, and so to increase the take-up and effectiveness of new policies. This paper develops an analytic framework for the trust relationships in Health 4.0, and through three use cases, assesses a medical policy, the introduction of a new technology, and the implications of that technology for the trust relationships. We integrate this assessment in a set of actionable recommendations, in particular that the trust framework should be part of the design methodology for developing and deploying medical applications. In a concluding discussion, we advocate that, in a post-pandemic world, IT to support policies and programmes to address widespread socio-medical problems with mental health, long Covid, physical inactivity and vaccine misinformation will be essential, and for that, strong trust relationships between all the stakeholders are absolutely critical.}, } @article {pmid35418390, year = {2022}, author = {Goldman, RD}, title = {Long COVID in children.}, journal = {Canadian family physician Medecin de famille canadien}, volume = {68}, number = {4}, pages = {263-265}, pmid = {35418390}, issn = {1715-5258}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Communicable Disease Control ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {QUESTION: Several physicians in our family medicine clinic noted a recent increase in the number of children with nonspecific symptoms after having had COVID-19. Based on the assumption that these children may have long COVID syndrome, what is the recommended treatment?

ANSWER: Lockdowns and isolation during the COVID-19 pandemic have affected the physical and mental health of children and adolescents. A recognized complication of COVID-19 is a post-COVID-19 syndrome (long COVID) that was initially reported in adults with an estimated prevalence of 10%. More recent reports on long COVID in children suggest a prevalence of 8% to 10%, but small cohorts, a range of symptoms, and challenges in defining the syndrome make accurately estimating the prevalence difficult. Furthermore, providers may find it challenging to differentiate between neuropsychiatric symptoms that are consequences of COVID-19 infection versus those that are a result of stress, anxiety, or changes in behaviour owing to restrictions associated with the pandemic. Until more evidence is available, management includes obtaining a detailed history, performing a comprehensive physical examination, and aiming to relieve symptoms while following up every 2 to 4 months.}, } @article {pmid35417745, year = {2022}, author = {Horwitz, RI and Conroy, AH and Cullen, MR and Colella, K and Mawn, M and Singer, BH and Sim, I}, title = {Long COVID and Medicine's Two Cultures.}, journal = {The American journal of medicine}, volume = {135}, number = {8}, pages = {945-949}, doi = {10.1016/j.amjmed.2022.03.020}, pmid = {35417745}, issn = {1555-7162}, mesh = {*COVID-19/complications ; Humans ; *Medicine ; Post-Acute COVID-19 Syndrome ; }, abstract = {Medicine has separated the two cultures of biological science and social science in research, even though they are intimately connected in the lives of our patients. To understand the cause, progression, and treatment of long COVID , biology and biography, the patient's lived experience, must be studied together.}, } @article {pmid35417544, year = {2022}, author = {Paneni, F and Patrono, C}, title = {Increased risk of incident diabetes in patients with long COVID.}, journal = {European heart journal}, volume = {43}, number = {22}, pages = {2094-2095}, doi = {10.1093/eurheartj/ehac196}, pmid = {35417544}, issn = {1522-9645}, mesh = {*COVID-19/complications/epidemiology ; *Diabetes Mellitus/epidemiology ; *Diabetes Mellitus, Type 2/complications/epidemiology ; Humans ; Incidence ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35417314, year = {2022}, author = {Beharry, M}, title = {Pediatric Anxiety and Depression in the Time of COVID-19.}, journal = {Pediatric annals}, volume = {51}, number = {4}, pages = {e154-e160}, doi = {10.3928/19382359-20220317-01}, pmid = {35417314}, issn = {1938-2359}, mesh = {Adolescent ; Anxiety/diagnosis/epidemiology/therapy ; *COVID-19/complications ; Child ; Depression/diagnosis/epidemiology/therapy ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {Pediatricians and other primary care clinicians are responsible for the screening of numerous health issues. As the coronavirus disease 2019 (COVID-19) pandemic persists, the adverse mental health effects on patients, their families, and the community at large are evident. Therefore, pediatricians are tasked with assessing, triaging, and initiating treatment for common mental health concerns such as anxiety and depression. Complicating the picture is long-COVID. This article reviews the epidemiology of pediatric and adolescent anxiety and depression and data about pediatric long-COVID. Additionally, strategies and tools for pediatricians and their office staff to address the mental health needs of their patients are outlined. [Pediatr Ann. 2022;51(4):e154-e160.].}, } @article {pmid35416359, year = {2022}, author = {Silva, CC and Bichara, CNC and Carneiro, FRO and Palacios, VRDCM and Berg, AVSVD and Quaresma, JAS and Magno Falcão, LF}, title = {Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach.}, journal = {Reviews in medical virology}, volume = {32}, number = {6}, pages = {e2355}, pmid = {35416359}, issn = {1099-1654}, mesh = {Humans ; *COVID-19/complications ; SARS-CoV-2 ; *Musculoskeletal System ; Muscles ; Post-Acute COVID-19 Syndrome ; }, abstract = {In long coronavirus disease 2019 (long COVID-19), involvement of the musculoskeletal system is characterised by the persistence or appearance of symptoms such as fatigue, muscle weakness, myalgia, and decline in physical and functional performance, even at 4 weeks after the onset of acute symptoms of COVID-19. Muscle injury biomarkers are altered during the acute phase of the disease. The cellular damage and hyperinflammatory state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to the persistence of symptoms, hypoxaemia, mitochondrial damage, and dysregulation of the renin-angiotensin system. In addition, the occurrence of cerebrovascular diseases, involvement of the peripheral nervous system, and harmful effects of hospitalisation, such as the use of drugs, immobility, and weakness acquired in the intensive care unit, all aggravate muscle damage. Here, we review the multifactorial mechanisms of muscle tissue injury, aggravating conditions, and associated sequelae in long COVID-19.}, } @article {pmid35415186, year = {2022}, author = {Lorent, N and Vande Weygaerde, Y and Claeys, E and Guler Caamano Fajardo, I and De Vos, N and De Wever, W and Salhi, B and Gyselinck, I and Bosteels, C and Lambrecht, BN and Everaerts, S and Verschraegen, S and Schepers, C and Demeyer, H and Heyns, A and Depuydt, P and Oeyen, S and Van Bleyenbergh, P and Godinas, L and Dupont, L and Hermans, G and Derom, E and Gosselink, R and Janssens, W and Van Braeckel, E}, title = {Prospective longitudinal evaluation of hospitalised COVID-19 survivors 3 and 12 months after discharge.}, journal = {ERJ open research}, volume = {8}, number = {2}, pages = {}, pmid = {35415186}, issn = {2312-0541}, abstract = {BACKGROUND: Long-term outcome data of coronavirus disease 2019 (COVID-19) survivors are needed to understand their recovery trajectory and additional care needs.

METHODS: A prospective observational multicentre cohort study was carried out of adults hospitalised with COVID-19 from March through May 2020. Workup at 3 and 12 months following admission consisted of clinical review, pulmonary function testing, 6-min walk distance (6MWD), muscle strength, chest computed tomography (CT) and quality of life questionnaires. We evaluated factors correlating with recovery by linear mixed effects modelling.

RESULTS: Of 695 patients admitted, 299 and 226 returned at 3 and 12 months, respectively (median age 59 years, 69% male, 31% severe disease). About half and a third of the patients reported fatigue, dyspnoea and/or cognitive impairment at 3 and 12 months, respectively. Reduced 6MWD and quadriceps strength were present in 20% and 60% at 3 months versus 7% and 30% at 12 months. A high anxiety score and body mass index correlated with poor functional recovery. At 3 months, diffusing capacity for carbon monoxide (D LCO) and total lung capacity were below the lower limit of normal in 35% and 18%, decreasing to 21% and 16% at 12 months; predictors of poor D LCO recovery were female sex, pre-existing lung disease, smoking and disease severity. Chest CT improved over time; 10% presented non-progressive fibrotic changes at 1 year.

CONCLUSION: Many COVID-19 survivors, especially those with severe disease, experienced limitations at 3 months. At 1 year, the majority showed improvement to almost complete recovery. To identify additional care or rehabilitation needs, we recommend a timely multidisciplinary follow-up visit following COVID-19 admission.}, } @article {pmid35413949, year = {2022}, author = {Whitaker, M and Elliott, J and Chadeau-Hyam, M and Riley, S and Darzi, A and Cooke, G and Ward, H and Elliott, P}, title = {Persistent COVID-19 symptoms in a community study of 606,434 people in England.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1957}, pmid = {35413949}, issn = {2041-1723}, support = {MR/L01341X/1/MRC_/Medical Research Council/United Kingdom ; 22184/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; 200187/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_17114/MRC_/Medical Research Council/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; MR/J008761/1/MRC_/Medical Research Council/United Kingdom ; RE/18/4/34215/BHF_/British Heart Foundation/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; 200861/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MR/V030841/1/MRC_/Medical Research Council/United Kingdom ; UNS32973/WT_/Wellcome Trust/United Kingdom ; MC_PC_19012/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; England/epidemiology ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.}, } @article {pmid35412189, year = {2022}, author = {Jacques, ET and Basch, CH and Park, E and Kollia, B and Barry, E}, title = {Long Haul COVID-19 Videos on YouTube: Implications for Health Communication.}, journal = {Journal of community health}, volume = {47}, number = {4}, pages = {610-615}, pmid = {35412189}, issn = {1573-3610}, mesh = {*COVID-19/complications/epidemiology ; *Health Communication ; Humans ; Language ; *Social Media ; Video Recording ; Post-Acute COVID-19 Syndrome ; }, abstract = {The term COVID-19 "long haul" originated on social media and was later studied by the scientific community. This study describes content related to persistent COVID-19 symptoms on YouTube. The 100 most viewed English-language videos identified with the keywords "COVID-19 long haul" were assessed for video origin, engagement, and content related to COVID-19 long-haul. The findings indicate that the majority of videos were uploaded by television or internet news (56%), followed by consumers (members of the public, 32%), health professionals (only 9%), and lastly by entertainment TV (non-news programs, 3%). Videos originating from entertainment TV were significantly more likely to be "liked" than videos from other sources. The most commonly mentioned long-haul symptoms in the videos were physical (fatigue, 73%; difficulty breathing/shortness of breath, 56%; and joint or muscle pain, 49%) and cognitive (difficulty thinking or concentrating; 69%). The case of COVID-19 long haul demonstrates that social media are significant fora whereon the public identify health concerns. It is necessary for healthcare professionals to assume an active and responsible role in social media.}, } @article {pmid35411333, year = {2022}, author = {Sanyaolu, A and Marinkovic, A and Prakash, S and Zhao, A and Balendra, V and Haider, N and Jain, I and Simic, T and Okorie, C}, title = {Post-acute Sequelae in COVID-19 Survivors: an Overview.}, journal = {SN comprehensive clinical medicine}, volume = {4}, number = {1}, pages = {91}, pmid = {35411333}, issn = {2523-8973}, abstract = {In the acute phase of SARS-CoV-2 infection, varying degrees of clinical manifestations have been noticed in patients. Some patients who recovered from the infection developed long-term effects which have become of interest to the scientific and medical communities, as it relates to pathogenesis and the multidisciplinary approach to treatment. Long COVID (long-term or long-haul) is the collective term used to define recovered individuals of SARS-CoV-2 infection who have presented with persistent COVID symptoms, as well as the emergence of disorders and complications. Following the review of literature from major scientific databases, this paper investigated long COVID and the resulting post-sequela effects on survivors, regardless of initial disease severity. The clinical manifestations and multisystem complications of the disease specifically, cardiovascular, neurologic and psychologic, hematologic, pulmonary, dermatologic, and other ailments were discussed. Patients with chronic COVID-19 were found to experience heart thrombosis leading to myocardial infarction, inflammation, lung fibrosis, stroke, venous thromboembolism, arterial thromboembolism, "brain fog", general mood dysfunctions, dermatological issues, and fatigue. As the disease continues to progress and spread, and with the emergence of new variants the management of these persisting symptoms will pose a challenge for healthcare providers and medical systems in the next period of the pandemic. However, more information is needed about long COVID, particularly concerning certain patient populations, variability in follow-up times, the prevalence of comorbidities, and the evolution of the spread of infection. Thus, continued research needs to be conducted concerning the disease pathology to develop preventative measures and management strategies to treat long COVID.}, } @article {pmid35411017, year = {2022}, author = {Sugiyama, A and Miwata, K and Kitahara, Y and Okimoto, M and Abe, K and E, B and Ouoba, S and Akita, T and Tanimine, N and Ohdan, H and Kubo, T and Nagasawa, A and Nakanishi, T and Takafuta, T and Tanaka, J}, title = {Long COVID occurrence in COVID-19 survivors.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6039}, pmid = {35411017}, issn = {2045-2322}, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {This cross-sectional study aimed to investigate the post-acute consequences of COVID-19. We conducted a self-administered questionnaire survey on sequelae, psychological distress (K6), impairments in work performance (WFun), and COVID-19-related experiences of stigma and discrimination in two designated COVID-19 hospitals in Hiroshima Prefecture, Japan, between August 2020 and March 2021. The prevalence of sequelae was calculated by age and COVID-19 severity. Factors independently associated with sequelae or psychological distress were identified using logistic regression analysis. Among 127 patients who had recovered from COVID-19, 52.0% had persistent symptoms at a median of 29 days [IQR 23-128] after COVID-19 onset. Among patients with mild COVID-19, 49.5% had sequelae. The most frequent symptoms were olfactory disorders (15.0%), taste disorders (14.2%), and cough (14.2%). Multivariate analysis showed that age was an independent risk factor for sequelae (adjusted odds ratios [AOR] for ≥ 60 years vs. < 40 years 3.63, p = 0.0165). Possible psychological distress was noted in 30.7% (17.9% of males and 45.0% of females). Female sex and the presence of sequelae were independent risk factors for psychological distress. Of all participants, 29.1% had possible impairments in work performance. Experiences of stigma and discrimination were reported by 43.3% of participants. This study revealed the significant impacts of Long COVID on health in local communities. A large-scale, long-term cohort study is desired.}, } @article {pmid35410933, year = {2022}, author = {Chandan, JS and Brown, K and Simms-Williams, N and Camaradou, J and Bashir, N and Heining, D and Aiyegbusi, OL and Turner, G and Cruz Rivera, S and Hotham, R and Nirantharakumar, K and Sivan, M and Khunti, K and Raindi, D and Marwaha, S and Hughes, SE and McMullan, C and Calvert, M and Haroon, S}, title = {Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.}, journal = {BMJ open}, volume = {12}, number = {4}, pages = {e057885}, pmid = {35410933}, issn = {2044-6055}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Bias ; *COVID-19/complications/therapy ; Humans ; Meta-Analysis as Topic ; Research Design ; SARS-CoV-2 ; Syndrome ; Systematic Reviews as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

AIMS: This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

METHODS AND ANALYSIS: Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

PROSPERO REGISTRATION NUMBER: The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).}, } @article {pmid35410644, year = {2022}, author = {Nielsen, SL and Ludwigsen, T and Johnsen, S and Miskowiak, KW}, title = {[Cognitive late sequelae of COVID-19].}, journal = {Ugeskrift for laeger}, volume = {184}, number = {15}, pages = {}, pmid = {35410644}, issn = {1603-6824}, mesh = {*COVID-19/complications ; Cognition ; Humans ; Neuropsychological Tests ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cognitive sequelae of COVID-19 including memory and concentration difficulties have been observed in 40-65% of persons who have been hospitalised with COVID-19 and 27-50% of non-hospitalised individuals. The cognitive impairments are associated with reduced work function and quality of life. This review recommends systematic cognition screening at long-COVID clinics using brief and feasible objective cognitive screeners, such as the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test B or similar tests with sensitivity to cognitive impairment in young populations.}, } @article {pmid35409815, year = {2022}, author = {Besnier, F and Bérubé, B and Malo, J and Gagnon, C and Grégoire, CA and Juneau, M and Simard, F and L'Allier, P and Nigam, A and Iglésies-Grau, J and Vincent, T and Talamonti, D and Dupuy, EG and Mohammadi, H and Gayda, M and Bherer, L}, title = {Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35409815}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Dyspnea/etiology ; Fatigue ; Humans ; Quality of Life ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {(1) Background: Cardiopulmonary and brain functions are frequently impaired after COVID-19 infection. Exercise rehabilitation could have a major impact on the healing process of patients affected by long COVID-19. (2) Methods: The COVID-Rehab study will investigate the effectiveness of an eight-week cardiopulmonary rehabilitation program on cardiorespiratory fitness (V˙O2max) in long-COVID-19 individuals. Secondary objectives will include functional capacity, quality of life, perceived stress, sleep quality (questionnaires), respiratory capacity (spirometry test), coagulation, inflammatory and oxidative-stress profile (blood draw), cognition (neuropsychological tests), neurovascular coupling and pulsatility (fNIRS). The COVID-Rehab project was a randomised clinical trial with two intervention arms (1:1 ratio) that will be blindly evaluated. It will recruit a total of 40 individuals: (1) rehabilitation: centre-based exercise-training program (eight weeks, three times per week); (2) control: individuals will have to maintain their daily habits. (3) Conclusions: Currently, there are no specific rehabilitation guidelines for long-COVID-19 patients, but preliminary studies show encouraging results. Clinicaltrials.gov (NCT05035628).}, } @article {pmid35409644, year = {2022}, author = {Aparisi, Á and Ybarra-Falcón, C and Iglesias-Echeverría, C and García-Gómez, M and Marcos-Mangas, M and Valle-Peñacoba, G and Carrasco-Moraleja, M and Fernández-de-Las-Peñas, C and Guerrero, ÁL and García-Azorín, D}, title = {Cardio-Pulmonary Dysfunction Evaluation in Patients with Persistent Post-COVID-19 Headache.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {7}, pages = {}, pmid = {35409644}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Female ; Headache/etiology ; Humans ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background (1): Headache is a prevalent symptom experienced during ongoing SARS-CoV-2 infection, but also weeks after recovery. Whether cardio-pulmonary dysfunction contributes causally to headache persistence is unknown. Methods (2): We conducted a case-control analysis nested in a prospective cohort study. Individuals were recruited from August 2020 to December 2020. Patients were grouped according to the presence or absence of long-COVID headache for three months after COVID-19 resolution. We compared demographic data, clinical variables, cardio-pulmonary laboratory biomarkers, quality of life, and cardio-pulmonary function between groups. Results (3): A cohort of 70 COVID-19 patients was evaluated. Patients with headaches (n = 10; 14.3%) were more frequently female (100% vs. 58.4%; p = 0.011) and younger (46.9 ± 8.45 vs. 56.13 ± 12 years; p = 0.023). No between-group differences in laboratory analysis, resting echocardiography, cardio-pulmonary exercise test, or pulmonary function tests were observed. Conclusion (4): In this exploratory study, no significant differences in cardio-pulmonary dysfunction were observed between patients with and without long-COVID headache during mid-term follow-up.}, } @article {pmid35407562, year = {2022}, author = {Yamamoto, Y and Otsuka, Y and Sunada, N and Tokumasu, K and Nakano, Y and Honda, H and Sakurada, Y and Hagiya, H and Hanayama, Y and Otsuka, F}, title = {Detection of Male Hypogonadism in Patients with Post COVID-19 Condition.}, journal = {Journal of clinical medicine}, volume = {11}, number = {7}, pages = {}, pmid = {35407562}, issn = {2077-0383}, abstract = {The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that “general fatigue” mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients’ backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT < 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = −0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.}, } @article {pmid35407054, year = {2022}, author = {Parker, JK and Methven, L and Pellegrino, R and Smith, BC and Gane, S and Kelly, CE}, title = {Emerging Pattern of Post-COVID-19 Parosmia and Its Effect on Food Perception.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {35407054}, issn = {2304-8158}, abstract = {Olfactory dysfunction is amongst the many symptoms of Long COVID. Whilst most people that experience smell loss post COVID-19 recover their sense of smell and taste within a few weeks, about 10% of cases experience long-term problems, and their smell recovery journey often begins a few months later when everyday items start to smell distorted. This is known as parosmia. The aim of this study was to identify the key food triggers of parosmic distortions and investigate the relationship between distortion and disgust in order to establish the impact of parosmia on diet and quality of life. In this cross-sectional study (n = 727), respondents experiencing smell distortions completed a questionnaire covering aspects of smell loss, parosmia and the associated change in valence of everyday items. There was a significant correlation between strength and disgust (p < 0.0001), and when the selected items were reported as distorted, they were described as either unpleasant or gag-inducing 84% of the time. This change in valence associated with loss of expected pleasure and the presence of strange tastes and burning sensations must certainly lead to changes in eating behaviours and serious longer-term consequences for mental health and quality of life.}, } @article {pmid35403679, year = {2022}, author = {Margalit, I and Yelin, D and Sagi, M and Rahat, MM and Sheena, L and Mizrahi, N and Gordin, Y and Agmon, H and Epstein, NK and Atamna, A and Tishler, O and Daitch, V and Babich, T and Abecasis, D and Yarom, Y and Kazum, S and Shitenberg, D and Baltaxe, E and Elkana, O and Shapira-Lichter, I and Leibovici, L and Yahav, D}, title = {Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {10}, pages = {1688-1697}, pmid = {35403679}, issn = {1537-6591}, mesh = {Humans ; Middle Aged ; Case-Control Studies ; *COVID-19/complications ; *Fatigue/epidemiology ; Risk Factors ; Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology.

METHODS: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue.

RESULTS: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003).

CONCLUSIONS: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology.

CLINICAL TRIALS REGISTRATION: NCT04851561.}, } @article {pmid35401774, year = {2022}, author = {Certain Curi, AC and Antunes Ferreira, AP and Calazans Nogueira, LA and Meziat Filho, NAM and Sá Ferreira, A}, title = {Osteopathy and physiotherapy compared to physiotherapy alone on fatigue in long COVID: Study protocol for a pragmatic randomized controlled superiority trial.}, journal = {International journal of osteopathic medicine : IJOM}, volume = {44}, number = {}, pages = {22-28}, pmid = {35401774}, issn = {1746-0689}, abstract = {OBJECTIVE: Fatigue is among the most common symptoms of the long-term effects of coronavirus (long COVID). This study aims to compare the effectiveness of osteopathic manipulative treatment (OMT) combined with physiotherapy treatment (PT) compared to PT alone on fatigue and functional limitations after two months post randomization in adults with long COVID.

METHODS: This is a study protocol for a two-arm, assessor-blinded, pragmatic randomized controlled superiority trial. Seventy-six participants will be randomly allocated to OMT + PT or PT. The PT includes usual care interventions including motor and respiratory exercises targeting cardiorespiratory and skeletal muscle functions. The OMT entails direct and indirect musculoskeletal, viceral and cranial techniques. Patients will be evaluated before and after a 2-month intervention program, and at 3-month follow-up session. Primary objectives comprise fatigue and functional limitations at 2-month post randomization as assessed by the fatigue severity scale and the Post-COVID Functional State scale. Secondary objectives comprise fatigue and functional limitations at 3 months, and the perceived change post-treatment as assessed by the Perceived Change Scale (PCS-patient).

REGISTRATION: This protocol was registered (NCT05012826) and received ethical approval (38342520.7.0000.5235). Participant recruitment began in August 2021 and is expected to conclude in July 2023. Publication of the results is anticipated in 2023.}, } @article {pmid35401574, year = {2022}, author = {Wang, JY and Zhang, W and Roehrl, VB and Roehrl, MW and Roehrl, MH}, title = {An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {831849}, pmid = {35401574}, issn = {1664-3224}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Autoantigens ; *COVID-19 ; Dermatan Sulfate ; Humans ; Lung/metabolism ; Proteins ; RNA ; SARS-CoV-2 ; }, abstract = {UNLABELLED: COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. We used DS-affinity proteomics to define the autoantigen-ome of lung fibroblasts and bioinformatics analyses to study the relationship between autoantigenic proteins and COVID-induced alterations. Using DS-affinity, we identified an autoantigen-ome of 408 proteins from human HFL1 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigen-ome have thus far been found to be altered at protein or RNA levels in SARS-CoV-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a connection between COVID infection and autoimmunity. The vast number of COVID-altered proteins with high intrinsic propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles suggests a need for long-term monitoring of autoimmunity in COVID. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic, such as "long COVID" syndrome.

SUMMARY SENTENCE: An autoantigen-ome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19.}, } @article {pmid35401523, year = {2022}, author = {Galán, M and Vigón, L and Fuertes, D and Murciano-Antón, MA and Casado-Fernández, G and Domínguez-Mateos, S and Mateos, E and Ramos-Martín, F and Planelles, V and Torres, M and Rodríguez-Mora, S and López-Huertas, MR and Coiras, M}, title = {Persistent Overactive Cytotoxic Immune Response in a Spanish Cohort of Individuals With Long-COVID: Identification of Diagnostic Biomarkers.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {848886}, pmid = {35401523}, issn = {1664-3224}, support = {R01 AI143567/AI/NIAID NIH HHS/United States ; }, mesh = {Biomarkers ; CD8-Positive T-Lymphocytes ; *COVID-19/complications ; Female ; Humans ; Immunity ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8[+] TEMRA cells, CD8[±]TCRγδ[+] cells, and NK cells with CD56[+]CD57[+]NKG2C[+] phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4[+] Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3[+] T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O[+] blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.}, } @article {pmid35401521, year = {2022}, author = {Tanunliong, G and Liu, AC and Kaweski, S and Irvine, M and Reyes, RC and Purych, D and Krajden, M and Morshed, M and Sekirov, I and Gantt, S and Skowronski, DM and Jassem, AN}, title = {Age-Associated Seroprevalence of Coronavirus Antibodies: Population-Based Serosurveys in 2013 and 2020, British Columbia, Canada.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {836449}, pmid = {35401521}, issn = {1664-3224}, mesh = {Aged ; Aged, 80 and over ; Antibodies, Viral ; British Columbia/epidemiology ; *COVID-19/complications/epidemiology ; Child ; Humans ; SARS-CoV-2 ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Older adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age.

METHODS: To assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets.

RESULTS: Samples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally.

CONCLUSION: Most people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.}, } @article {pmid35398877, year = {2022}, author = {Ohla, K and Veldhuizen, MG and Green, T and Hannum, ME and Bakke, AJ and Moein, ST and Tognetti, A and Postma, EM and Pellegrino, R and Hwang, DLD and Albayay, J and Koyama, S and Nolden, AA and Thomas-Danguin, T and Mucignat-Caretta, C and Menger, NS and Croijmans, I and Ã-ztà Rk, L and YanÄ K, H and Pierron, D and Pereda-Loth, V and Nunez-Parra, A and Martinez Pineda, AM and Gillespie, D and Farruggia, MC and Cecchetto, C and Fornazieri, MA and Philpott, C and Voznessenskaya, V and Cooper, KW and Rohlfs Dominguez, P and Calcinoni, O and de Groot, J and Boesveldt, S and Bhutani, S and Weir, EM and Exten, C and Joseph, PV and Parma, V and Hayes, JE and Niv, MY}, title = {A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.}, journal = {Rhinology}, volume = {60}, number = {3}, pages = {207-217}, pmid = {35398877}, issn = {0300-0729}, support = {Z99 AA999999/ImNIH/Intramural NIH HHS/United States ; ZIA AA000138/ImNIH/Intramural NIH HHS/United States ; ZIA AA000136/ImNIH/Intramural NIH HHS/United States ; ZIA AA000139/ImNIH/Intramural NIH HHS/United States ; ZIA AA000135/ImNIH/Intramural NIH HHS/United States ; T32 DC000014/DC/NIDCD NIH HHS/United States ; F32 DC020380/DC/NIDCD NIH HHS/United States ; ZIA AA000137/ImNIH/Intramural NIH HHS/United States ; F32 DC020100/DC/NIDCD NIH HHS/United States ; }, mesh = {Male ; Humans ; Female ; *COVID-19/complications ; Smell ; *Ageusia ; Anosmia/etiology ; SARS-CoV-2 ; Cohort Studies ; COVID-19 Testing ; Follow-Up Studies ; Post-Acute COVID-19 Syndrome ; *Olfaction Disorders/epidemiology/etiology/diagnosis ; }, abstract = {BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection.

METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness.

RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2.

CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.}, } @article {pmid35397801, year = {2022}, author = {The Lancet Diabetes Endocrinology, }, title = {Long COVID: the elephant in the room.}, journal = {The lancet. Diabetes & endocrinology}, volume = {10}, number = {5}, pages = {297}, doi = {10.1016/S2213-8587(22)00111-5}, pmid = {35397801}, issn = {2213-8595}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35393771, year = {2022}, author = {Eldokla, AM and Mohamed-Hussein, AA and Fouad, AM and Abdelnaser, MG and Ali, ST and Makhlouf, NA and Sayed, IG and Makhlouf, HA and Shah, J and Aiash, H}, title = {Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.}, journal = {Annals of clinical and translational neurology}, volume = {9}, number = {6}, pages = {778-785}, pmid = {35393771}, issn = {2328-9503}, mesh = {*COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; *Orthostatic Intolerance ; Prevalence ; *Primary Dysautonomias/epidemiology/etiology ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking.

OBJECTIVE: To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome.

METHODS: We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19.

RESULTS: We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001).

CONCLUSIONS: Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.}, } @article {pmid35391879, year = {2022}, author = {Comelli, A and Viero, G and Bettini, G and Nobili, A and Tettamanti, M and Galbussera, AA and Muscatello, A and Mantero, M and Canetta, C and Martinelli Boneschi, F and Arighi, A and Brambilla, P and Vecchi, M and Lampertico, P and Bonfanti, P and Contoli, M and Blasi, F and Gori, A and Bandera, A}, title = {Patient-Reported Symptoms and Sequelae 12 Months After COVID-19 in Hospitalized Adults: A Multicenter Long-Term Follow-Up Study.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {834354}, pmid = {35391879}, issn = {2296-858X}, abstract = {OBJECTIVE: Our knowledge on the long-term consequences of COVID-19 is still scarce despite the clinical relevance of persisting syndrome. The aim of this study was to analyze patient-reported outcomes, including assessment by specific questionnaires of health impairment and symptoms.

METHODS: This is a prospective, observational and multicenter cohort study coordinated by Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico di Milano and Istituto di Ricerche Farmacologiche Mario Negri IRCCS including eight hospitals located in North and Central Italy. A telephone interview to assess rehospitalization, access to health care resources, general health status subjective evaluation, and symptoms was performed at 12 months after the discharge in patients admitted to hospital because of COVID-19 from February 2020 to the end of May 2020.

RESULTS: Among the 776 patients discharged alive, 44 (5.7%) died, 456 subjects (58.8%) completed the questionnaire and 276 (35.6%) were not reachable or refused to join the telephone interview. The mean age of the study population was 59.4 years (SD 14.1), 69.8% of individuals needed oxygen support during hospitalization and 10.4% were admitted to ICU. Overall, 91.7% of participants reported at least one symptom/sequela at 12 months. Exertional dyspnea (71.7%), fatigue (54.6%), and gastrointestinal symptoms (32.8%) were the most reported ones. Health issues after discharge including hospitalization or access to emergency room were described by 19.4% of subjects. Female and presence of comorbidities were independent predictors of whealth impairment and presence of ≥2 symptoms/sequelae after 12 months from hospitalization for COVID-19.

CONCLUSIONS: Patient-reported symptoms and sequelae, principally dyspnea and fatigue, are found in most individuals even 12 months from COVID-19 hospitalization. Long-term follow-up based on patient-centered outcome can contribute to plan tailored interventions.}, } @article {pmid35390511, year = {2022}, author = {Rejdak, K and Fiedor, P and Bonek, R and Goch, A and Gala-Błądzińska, A and Chełstowski, W and Łukasiak, J and Kiciak, S and Dąbrowski, P and Dec, M and Król, ZJ and Papuć, E and Zasybska, A and Segiet, A and Grieb, P}, title = {The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.}, journal = {Contemporary clinical trials}, volume = {116}, number = {}, pages = {106755}, pmid = {35390511}, issn = {1559-2030}, mesh = {Amantadine/therapeutic use ; *COVID-19/complications ; Humans ; *Respiratory Insufficiency ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications.

METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine.

CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome.

CLINICAL TRIAL REGISTRATION: www.

CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).}, } @article {pmid35390469, year = {2022}, author = {Yang, CP and Chang, CM and Yang, CC and Pariante, CM and Su, KP}, title = {Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.}, journal = {Brain, behavior, and immunity}, volume = {103}, number = {}, pages = {19-27}, pmid = {35390469}, issn = {1090-2139}, support = {G108/603/MRC_/Medical Research Council/United Kingdom ; MR/J002739/1/MRC_/Medical Research Council/United Kingdom ; MR/N029488/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Fatty Acids ; *Fatty Acids, Omega-3/therapeutic use ; Humans ; Hypothalamo-Hypophyseal System ; Inflammation/drug therapy ; Pituitary-Adrenal System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.}, } @article {pmid35388764, year = {2022}, author = {Fajloun, Z and Kovacic, H and Annweiler, C and Wu, Y and Cao, Z and Sabatier, JM}, title = {SARS-CoV-2-Induced Neurological Disorders in Symptomatic Covid-19 and Long Covid Patients: Key Role of Brain Renin-Angiotensin System.}, journal = {Infectious disorders drug targets}, volume = {22}, number = {5}, pages = {e060422203203}, doi = {10.2174/1871526522666220406124618}, pmid = {35388764}, issn = {2212-3989}, mesh = {Brain/diagnostic imaging ; *COVID-19/complications ; Humans ; *Nervous System Diseases ; Renin-Angiotensin System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35388183, year = {2022}, author = {Hashimoto, Y and Suzuki, T and Hashimoto, K}, title = {Comments to "Fluvoxamine and long COVID-19: a new role for sigma-1 receptor (S1R) agonists" by Khani and Entezari-Maleki.}, journal = {Molecular psychiatry}, volume = {27}, number = {9}, pages = {3563-3564}, pmid = {35388183}, issn = {1476-5578}, mesh = {Humans ; Fluvoxamine/therapeutic use ; *COVID-19 ; *Receptors, sigma ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Sigma-1 Receptor ; }, } @article {pmid35388182, year = {2022}, author = {Khani, E and Entezari-Maleki, T}, title = {Fluvoxamine and long COVID-19; a new role for sigma-1 receptor (S1R) agonists.}, journal = {Molecular psychiatry}, volume = {27}, number = {9}, pages = {3562}, pmid = {35388182}, issn = {1476-5578}, mesh = {Humans ; Fluvoxamine/therapeutic use ; *COVID-19 ; *Receptors, sigma/agonists ; COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; Sigma-1 Receptor ; }, } @article {pmid35385677, year = {2022}, author = {Faghy, MA and Maden-Wilkinson, T and Arena, R and Copeland, RJ and Owen, R and Hodgkins, H and Willmott, A}, title = {COVID-19 patients require multi-disciplinary rehabilitation approaches to address persisting symptom profiles and restore pre-COVID quality of life.}, journal = {Expert review of respiratory medicine}, volume = {16}, number = {5}, pages = {595-600}, doi = {10.1080/17476348.2022.2063843}, pmid = {35385677}, issn = {1747-6356}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Quality of Life ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID diagnosis is prominent, and our attention must support those experiencing debilitating and long-standing symptoms. To establish patient pathways, we must consider the societal and economic impacts of sustained COVID-19. Accordingly, we sought to determine the pertinent areas impacting quality of life (QoL) following a COVID-19 infection.

RESEARCH METHODS: Three hundred and eighty-one participants completed a web-based survey (83% female, 17% male) consisting of 70 questions across 7 sections (demographics, COVID-19 symptoms; QoL; sleep quality; breathlessness; physical activity and mental health). Mean age, height, body mass and body mass index (BMI) were 42 ± 12 years, 167.6 ± 10.4 cm, 81.2 ± 22.2 kg, and 29.1 ± 8.4 kg.m[2], respectively.

RESULTS: Participant health was reduced because of COVID-19 symptoms ('Good health' to 'Poor health' [P < 0.001]). Survey respondents who work reported ongoing issues with performing moderate (83%) and vigorous (79%) work-related activities.

CONCLUSIONS: COVID-19 patients report reduced capacity to participate in activities associated with daily life, including employment activities. Bespoke COVID-19 support pathways must consider multi-disciplinary approaches that address the holistic needs of patients to restore pre-pandemic quality of life and address experienced health and wellbeing challenges.Plain Language Summary: The long-term impact of long-COVID has a dramatic impact upon daily activities and lifestyle. The development of bespoke support pathways to support patients must address the physical and psychological considerations to adequately restore pre-COVID quality of life and address broader societal and economic implications, especially for those that are of working age.}, } @article {pmid35385125, year = {2022}, author = {Finsterer, J}, title = {Small fiber neuropathy underlying dysautonomia in COVID-19 and in post-SARS-CoV-2 vaccination and long-COVID syndromes.}, journal = {Muscle & nerve}, volume = {65}, number = {6}, pages = {E31-E32}, pmid = {35385125}, issn = {1097-4598}, mesh = {*COVID-19/complications/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; *Primary Dysautonomias/etiology ; SARS-CoV-2 ; *Small Fiber Neuropathy/etiology ; Syndrome ; Vaccination/adverse effects ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35383586, year = {2022}, author = {Carson, E and Hemenway, AN}, title = {A Scoping Review of Pharmacological Management of Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2021.}, journal = {American journal of therapeutics}, volume = {29}, number = {3}, pages = {e305-e321}, pmid = {35383586}, issn = {1536-3686}, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC), or long-COVID, are signs and symptoms that persist after the acute phase of Coronavirus disease 2019 infection has passed. PASC is newly recognized, and research is ongoing to answer questions about pathology, symptoms, diagnosis, and optimal treatment.

AREAS OF UNCERTAINTY: Use of pharmacologic treatment for symptoms of PASC is currently evolving. This scoping review aims to assess medical literature for any evidence supporting or refuting use of any medications to specifically treat PASC.

DATA SOURCES: PubMed, EMBASE, Web of Science, and gray literature sources were searched for any study of medication use for PASC. Studies were included if they described medication use in patients with PASC. There were no exclusion criteria based on study type or if results were reported. Studies were divided into completed works and ongoing research.

RESULTS: Fifty-two records were included in final analysis from an initial 3524 records found, including 2 randomized controlled trials, 7 prospective, open-label or observational studies, 14 case reports or case series, 1 survey, 1 correspondence, 1 retrospective analysis, and 26 studies in progress. Seven of the 26 completed works investigate ivabradine or beta-blockers, whereas 7 investigate local or systemic corticosteroids. Three investigate multi-ingredient nutritional supplements. The other 9 completed works as well as the 26 studies in progress investigate a wide variety of other treatments including drugs in development, drugs used for other conditions, herbals, supplements, and vitamins.

CONCLUSIONS: There is limited, but evolving, literature on medication treatment for PASC. Providers who opt to use pharmacologic therapy for PASC need to be vigilant in their knowledge of these evolving data.}, } @article {pmid35383311, year = {2022}, author = {Brodin, P and Casari, G and Townsend, L and O'Farrelly, C and Tancevski, I and Löffler-Ragg, J and Mogensen, TH and Casanova, JL and , }, title = {Studying severe long COVID to understand post-infectious disorders beyond COVID-19.}, journal = {Nature medicine}, volume = {28}, number = {5}, pages = {879-882}, pmid = {35383311}, issn = {1546-170X}, support = {MR/S032304/1/MRC_/Medical Research Council/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*COVID-19/complications ; Humans ; Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35383197, year = {2022}, author = {Tran, VT and Porcher, R and Pane, I and Ravaud, P}, title = {Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1812}, pmid = {35383197}, issn = {2041-1723}, mesh = {Adult ; *COVID-19/complications ; Humans ; Prospective Studies ; SARS-CoV-2 ; Taste Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {About 10% of people infected by severe acute respiratory syndrome coronavirus 2 experience post COVID-19 disease. We analysed data from 968 adult patients (5350 person-months) with a confirmed infection enroled in the ComPaRe long COVID cohort, a disease prevalent prospective e-cohort of such patients in France. Day-by-day prevalence of post COVID-19 symptoms was determined from patients' responses to the Long COVID Symptom Tool, a validated self-reported questionnaire assessing 53 symptoms. Among patients symptomatic after 2 months, 85% still reported symptoms one year after their symptom onset. Evolution of symptoms showed a decreasing prevalence over time for 27/53 symptoms (e.g., loss of taste/smell); a stable prevalence over time for 18/53 symptoms (e.g., dyspnoea), and an increasing prevalence over time for 8/53 symptoms (e.g., paraesthesia). The disease impact on patients' lives began increasing 6 months after onset. Our results are of importance to understand the natural history of post COVID-19 disease.}, } @article {pmid35382075, year = {2022}, author = {Raciti, L and Arcadi, FA and Calabrò, RS}, title = {Could Palmitoylethanolamide Be an Effective Treatment for Long-COVID-19? Hypothesis and Insights in Potential Mechanisms of Action and Clinical Applications.}, journal = {Innovations in clinical neuroscience}, volume = {19}, number = {1-3}, pages = {19-25}, pmid = {35382075}, issn = {2158-8333}, abstract = {COVID-19 is highly transmissive and contagious disease with a wide spectrum of clinicopathological issues, including respiratory, vasculo-coagulative, and immune disorders. In some cases of COVID-19, patients can be characterized by clinical sequelae with mild-to-moderate symptoms that persist long after the resolution of the acute infection, known as long-COVID, potentially affecting their quality of life. The main symptoms of long-COVID include persistent dyspnea, fatigue and weakness (that are typically out of proportion, to the degree of ongoing lung damage and gas exchange impairment), persistence of anosmia and dysgeusia, neuropsychiatric symptoms, and cognitive dysfunctions (such as brain fog or memory lapses). The appropriate management and prevention of potential long-COVID sequelae is still lacking. It is also believed that long-term symptoms of COVID-19 are related to an immunity over-response, namely a cytokine storm, involving the release of pro-inflammatory interleukins, monocyte chemoattractant proteins, and tissue necrosis factors. Palmitoylethanolamide (PEA) shows affinity for vanilloid receptor 1 and for cannabinoid-like G protein-coupled receptors, enhancing anandamide activity by means of an entourage effect. Due to its anti-inflammatory properties, PEA has been recently used as an early add-on therapy for respiratory problems in patients with COVID-19. It is believed that PEA mitigates the cytokine storm modulating cell-mediated immunity, as well as counteracts pain and oxidative stress. In this article, we theorize that PEA could be a potentially effective nutraceutical to treat long-COVID, with regard to fatigue and myalgia, where a mythocondrial dysfunction is hypothesizable.}, } @article {pmid35381597, year = {2022}, author = {Fernández-de-Las-Peñas, C and Ryan-Murua, P and Rodríguez-Jiménez, J and Palacios-Ceña, M and Arendt-Nielsen, L and Torres-Macho, J}, title = {Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors.}, journal = {Respiration; international review of thoracic diseases}, volume = {101}, number = {7}, pages = {658-665}, pmid = {35381597}, issn = {1423-0356}, mesh = {Biomarkers ; *COVID-19/complications ; Cohort Studies ; Dyspnea/etiology ; Fatigue/epidemiology/etiology ; Female ; Hospitalization ; Hospitals ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The aim of this study was to investigate the association between serological biomarkers at the acute phase of infection at hospital admission with the development of long-term post-COVID fatigue and dyspnea.

METHODS: A cohort study including patients hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the outbreak (from March 20 to June 30, 2020) was conducted. Hospitalization data, clinical data, and eleven serological biomarkers were systematically collected at hospital admission. Patients were scheduled for an individual telephone interview after hospital discharge for collecting data about the presence of post-COVID fatigue and dyspnea.

RESULTS: A total of 412 patients (age: 62 years, standard deviation: 15 years; 47.5% women) were assessed with a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID fatigue and dyspnea was 72.8% and 17.2% at 6 months and 45.4% and 13.6% at 12 months after hospital discharge, respectively. Patients exhibiting post-COVID fatigue at 6 or 12 months exhibited a lower hemoglobin level, higher lymphocyte count, and lower neutrophil and platelets counts (all, p < 0.05), whereas those exhibiting post-COVID dyspnea at 6 or 12 months had a lower platelet count and lower alanine transaminase, aspartate transaminase, and lactate dehydrogenase (LDH) levels (all, p < 0.05) than those not developing post-COVID fatigue or dyspnea, respectively. The multivariate regression analyses revealed that a lower platelet count and lower LDH levels were associated but just explaining 4.5% of the variance, of suffering from post-COVID fatigue and dyspnea, respectively.

CONCLUSION: Some serological biomarkers were slightly different in patients exhibiting post-COVID fatigue or dyspnea, but they could not explain the long-COVID problems in those patients.}, } @article {pmid35381027, year = {2022}, author = {Kuodi, P and Gorelik, Y and Edelstein, M}, title = {Characterisation of the long-term physical and mental health consequences of SARS-CoV-2 infection: A systematic review and meta-analysis protocol.}, journal = {PloS one}, volume = {17}, number = {4}, pages = {e0266232}, pmid = {35381027}, issn = {1932-6203}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Mental Health ; Meta-Analysis as Topic ; SARS-CoV-2 ; Systematic Reviews as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: As of July 2021, there has been more than 185 million documented cases of the novel coronavirus (SARS-CoV-2) infections and more than 4 million deaths globally. Despite more than 90% of documented cases being classified as "recovered" from SARS-CoV-2 infection, a proportion of patients reported a wide variety of persisting symptoms after the initial onset or acute phase of the infection, often referred to as "Long Covid". As data on the symptomatology of post-acute SARS-CoV-2 infection gradually becomes available, there is an urgent need to organise and synthesise the data in order to define what constitutes Long Covid and assist with its management in clinical and community settings.

METHODS: This protocol follows the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines. A comprehensive literature search strategy will be developed in accordance with the Cochrane highly sensitive search guidelines. The following electronic databases will be searched for studies to include in the systematic review and meta-analysis: MEDLINE (via PubMed), Scopus, Google Scholar, Web of Science (Web of Knowledge), Science direct, EMBASE, Mednar, Psych INFO, and EBSCOhost. Dual screening will be applied at every screening stage. Two reviewers will independently screen titles, abstracts and full text of potentially eligible studies following the predefined inclusion and exclusion criteria in order to select studies to include in the review. As heterogeneity is anticipated between the included studies, data will be pooled in a meta-analysis using a random effects model. A clustering analytic approach will be applied to identify symptoms groupings and assign the symptoms into clusters. R statistical software will be used for the meta-analysis. Highly heterogenous data will be synthesised narratively. The studies will be assessed, for quality using quality assessment tools appropriate for each study design. Two reviewers will independently undertake the quality of studies assessments.

DISSEMINATION PLANS: Findings of the systematic review will be disseminated through a peer-reviewed publication and presentation of findings at conferences, workshops and government and private sector stakeholder engagement meetings.

CLINICAL TRIAL REGISTRATION: PROSPERO registration number: CRD4202126589. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD4202126589.}, } @article {pmid35380318, year = {2022}, author = {Bitirgen, G and Korkmaz, C and Zamani, A and Iyisoy, MS and Kerimoglu, H and Malik, RA}, title = {Abnormal quantitative pupillary light responses following COVID-19.}, journal = {International ophthalmology}, volume = {42}, number = {9}, pages = {2847-2854}, pmid = {35380318}, issn = {1573-2630}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; France ; Humans ; Light ; Pupil ; Reflex, Pupillary ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: To characterize alterations in pupillary light reflex responses in subjects following coronavirus disease 2019 (COVID-19), especially those with long-COVID.

METHODS: Thirty-five subjects with previous COVID-19 and 30 healthy control participants were enrolled in this cross-sectional comparative study. An infrared dynamic pupillometry system (MonPack One; Metrovision, France) was used to quantify pupillary light responses. The National Institute for Health and Care Excellence (NICE) long-COVID questionnaire was used to identify persisting symptoms at least 4 weeks after acute COVID-19.

RESULTS: The median time after the diagnosis of acute COVID-19 was 4.0 (2.0-5.0) months. There was an increase in the latency of pupil contraction (P = 0.001) and a reduction in the duration of pupil contraction (P = 0.039) in post-COVID-19 subjects compared to healthy controls. No significant differences were observed in the initial pupil diameter, amplitude and velocity of pupil contraction or latency, velocity and duration of pupil dilation. Long-COVID was present in 25/35 (71%) subjects and their duration of pupil contraction was reduced compared to subjects without long-COVID (P = 0.009). The NICE long-COVID questionnaire total score (ρ = - 0.507; P = 0.002) and neurological score (ρ = - 0.412; P = 0.014) correlated with the duration of pupil contraction and the total score correlated with the latency of dilation (ρ = - 0.352; P = 0.038).

CONCLUSION: Dynamic pupillometry reveals significant alterations in contractile pupillary light responses, indicative of parasympathetic dysfunction after COVID-19.}, } @article {pmid35379408, year = {2022}, author = {Sharma, P and Bharti, S and Garg, I}, title = {Post COVID fatigue: Can we really ignore it?.}, journal = {The Indian journal of tuberculosis}, volume = {69}, number = {2}, pages = {238-241}, pmid = {35379408}, issn = {0019-5707}, mesh = {*COVID-19/complications ; Fatigue/etiology ; *Fatigue Syndrome, Chronic/complications/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID, also referred to as post-acute COVID-19, chronic COVID-19, post-COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or after acute COVID-19 illness, continue for ≥12 weeks, and are not explained by an alternative diagnosis. It is not yet known whether "long-COVID" represents a new syndrome unique to COVID-19 or overlaps with recovery from similar illnesses. It's difficult for physicians to predict when symptoms will improve as it varies differently in different people. Patient's recovery depends on various factors including age, associated comorbidities, severity of COVID-19 infection. Some symptoms, like fatigue, might continue even while others improve or go away. This review addresses the pathogenesis, presentation of post covid fatigue, its severity and its management.}, } @article {pmid35378898, year = {2022}, author = {Calcaterra, G and Fanos, V and Cataldi, L and Cugusi, L and Crisafulli, A and Bassareo, PP}, title = {Need for resuming sports and physical activity for children and adolescents following COVID-19 infection.}, journal = {Sport sciences for health}, volume = {18}, number = {4}, pages = {1179-1185}, pmid = {35378898}, issn = {1824-7490}, abstract = {INTRODUCTION: A decline in sports activities among children and adolescents was noted during the stay-at-home restrictions imposed by COVID-19. With the easing of restrictions, physical activities are being resumed.

EVIDENCE ACQUISITION: A data search was conducted to identify the role of parents in resuming sporting activities, the risks and benefits of doing so, the physical examination to be conducted prior to physical activity, the existence of guidelines/protocols for return to sports and physical activity, the role of comorbidities in influencing the restart of the same.

EVIDENCE SYNTHESIS: Parents should consult the child's physician prior to allowing he/she to resume physical exercise. In preparation for this, a careful physical examination should be performed. Children with COVID-19, even if asymptomatic, should not resume any physical activity until at least 10 days after testing positive. Those with moderate or severe COVID-19 should be referred for cardiological evaluation. The level of activity should be resumed gradually, as per the GRTP protocol. Athletes with a positive COVID-19 test in the presence of concomitant medical conditions (diabetes, cardiovascular or respiratory or renal disease) should undergo medical evaluation prior to adhering to a GRTP. Those with complicated COVID19 infection or long Covid may need additional investigations.

CONCLUSIONS: While there is no doubt that it will bring multiple benefits in terms of general health, returning to play sport should be gradual and preceded by an accurate physical examination in those young subjects previously affected by the coronavirus disease, especially when their heart and/or lungs and/or kidneys were affected.}, } @article {pmid35378724, year = {2022}, author = {Tulp, E and Wagenaar, J}, title = {[Not Available].}, journal = {Nursing}, volume = {28}, number = {4}, pages = {39-44}, doi = {10.1007/s41193-022-0046-y}, pmid = {35378724}, issn = {2468-1431}, } @article {pmid35373863, year = {2022}, author = {Mannucci, PM and Nobili, A and Tettamanti, M and D'Avanzo, B and Galbussera, AA and Remuzzi, G and Fortino, I and Leoni, O and Harari, S}, title = {Impact of the post-COVID-19 condition on health care after the first disease wave in Lombardy.}, journal = {Journal of internal medicine}, volume = {292}, number = {3}, pages = {450-462}, pmid = {35373863}, issn = {1365-2796}, mesh = {*COVID-19/epidemiology ; Delivery of Health Care ; Humans ; Intensive Care Units ; Pandemics ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: Lombardy was affected in the early months of 2020 by the SARS-CoV-2 pandemic with very high morbidity and mortality. The post-COVID-19 condition and related public health burden are scarcely known.

SETTING AND DESIGN: Using the regional population administrative database including all the 48,932 individuals who survived COVID-19 and became polymerase-chain-reaction negative for SARS-CoV-2 by 31 May 2020, incident mortality, rehospitalizations, attendances to hospital emergency room, and outpatient medical visits were evaluated over a mid-term period of 6 months in 20,521 individuals managed at home, 26,016 hospitalized in medical wards, and 1611 in intensive care units (ICUs). These data were also evaluated in the corresponding period of 2019, when the region was not yet affected by the pandemic. Other indicators and proxies of the health-care burden related to the post-COVID condition were also evaluated.

MAIN RESULTS: In individuals previously admitted to the ICU and medical wards, rehospitalizations, attendances to hospital emergency rooms, and out-patient medical visits were much more frequent in the 6-month period after SARS-CoV-2 negativization than in the same prepandemic period. Performances of spirometry increased more than 50-fold, chest CT scans 32-fold in ICU-admitted cases and 5.5-fold in non-ICU cases, and electrocardiography 5.6-fold in ICU cases and twofold in non-ICU cases. Use of drugs and biochemical tests increased in all cases.

CONCLUSIONS: These results provide a real-life picture of the post-COVID condition and of its effects on the increased consumption of health-care resources, considered proxies of comorbidities.}, } @article {pmid35373158, year = {2022}, author = {Kaatz, M and Springer, S and Schubert, R and Zieger, M}, title = {Representation of long COVID syndrome in the awareness of the population is revealed by Google Trends analysis.}, journal = {Brain, behavior, & immunity - health}, volume = {22}, number = {}, pages = {100455}, pmid = {35373158}, issn = {2666-3546}, abstract = {In some COVID-19 patients, symptoms persist for several weeks and sometimes, after the acute disease phase, these patients develop new symptoms, which then represents a transition into the so-called long COVID. The exact demarcation of the terms and generally applicable definitions are still discussed, but the phenomenon is most commonly referred to as long COVID. In this study, Google Trends data have been used to track levels of public awareness for long COVID and some important symptoms during the course of the COVID-19 pandemic. The results of this analysis clearly demonstrate the public interest in the new topic of long COVID, as documented by a corresponding search volume. This is related to the disease COVID-19, which is being spread by the corona pandemic. Relevant symptoms for COVID-19 or long COVID, for example ageusia and anosmia, only started to receive more public attention during the pandemic. Therefore, Google Trends is a useful tool to demonstrate the population's awareness of certain infodemiological topics like long COVID.}, } @article {pmid35370620, year = {2022}, author = {Guo, P and Benito Ballesteros, A and Yeung, SP and Liu, R and Saha, A and Curtis, L and Kaser, M and Haggard, MP and Cheke, LG}, title = {COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {804937}, pmid = {35370620}, issn = {1663-4365}, abstract = {COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID - the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on "objective" cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.}, } @article {pmid35370617, year = {2022}, author = {Guo, P and Benito Ballesteros, A and Yeung, SP and Liu, R and Saha, A and Curtis, L and Kaser, M and Haggard, MP and Cheke, LG}, title = {COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study.}, journal = {Frontiers in aging neuroscience}, volume = {14}, number = {}, pages = {804922}, pmid = {35370617}, issn = {1663-4365}, abstract = {Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing "Long COVID"-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not. We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.}, } @article {pmid35370531, year = {2022}, author = {Zwick, RH}, title = {[Outpatient pulmonary rehabilitation].}, journal = {Der Pneumologe}, volume = {19}, number = {3}, pages = {150-157}, pmid = {35370531}, issn = {1613-5636}, abstract = {BACKGROUND: Outpatient pulmonary rehabilitation (PR) plays a central role in the integrative care of patients with pulmonary diseases.

MATERIAL AND METHODS: The article gives an overview of the recent evidence on outpatient PR in various diseases, in various settings including the cost-effectiveness. This is based on a selective literature search in the PubMed and Medline databanks, current expert opinions and clinical experiences.

RESULTS: Early rehabilitation after exacerbation in COPD patients leads to a reduction of rehospitalizations (hazard ratio 0.83) and to a reduction of mortality (hazard ratio 0.63) over a period of 12 months. Telerehabilitation is a promising future perspective in specific settings. Recent publications on bronchiectasis, interstitial lung diseases and pulmonary hypertension could confirm the safety and feasibility of outpatient PR and the cost-effectiveness could be demonstrated. Also, the evidence for inpatient as well as outpatient PR settings for patients with post-COVID and long COVID is growing.

CONCLUSION: There is growing equivalence with respect to the evidence on PR, independent of whether it is carried out in an outpatient or inpatient setting.}, } @article {pmid35369686, year = {2022}, author = {Baig, AM}, title = {Correlating Biochemical and Structural Changes in the Brain with Clinical Features in COVID-19.}, journal = {ACS chemical neuroscience}, volume = {13}, number = {8}, pages = {1105-1107}, doi = {10.1021/acschemneuro.2c00164}, pmid = {35369686}, issn = {1948-7193}, mesh = {Brain/diagnostic imaging ; *COVID-19 ; Humans ; *Nervous System Diseases ; SARS-CoV-2 ; }, abstract = {With emerging reports of the deleterious effects of SARS-CoV-2 reflecting as neurological deficits in COVID-19, the biochemical and morphological changes it casts on the brain are also being investigated. This is an important niche of research as it is expected to predict and relate the neurological clinical features in the acute phase and chronic syndromic forms of COVID-19. Here debated are the biochemical and structural changes that can be related to the neurological manifestations in COVID-19.}, } @article {pmid35368611, year = {2021}, author = {Rodríguez-Alfonso, B and Ruiz Solís, S and Silva-Hernández, L and Pintos Pascual, I and Aguado Ibáñez, S and Salas Antón, C}, title = {[[18]F-FDG-PET/CT in SARS-CoV-2 infection and its sequelae].}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {40}, number = {5}, pages = {299-309}, pmid = {35368611}, issn = {2253-8070}, mesh = {*COVID-19/complications/diagnostic imaging ; Fluorodeoxyglucose F18 ; Humans ; Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In recent months, much of the scientific efforts have focused on research on SARSCoV-2 infection and its consequences in humans. Still, many aspects remain unknown. It is known that the damage caused by SARS-CoV-2 is multifactorial and that its extension goes beyond lung inflammation and the acute phase, with the appearance of numerous complications and sequelae. To date, knowledge about the usefulness of [18]F-FDG-PET/CT in the acute phase has been limited to the incidental detection of SARS-CoV-2 unsuspected pneumonia. Recent studies have been appearing collecting the findings of [18]F-FDG- PET/CT in long COVID-19 or persistent COVID-19 state as well as the alterations caused after mass vaccination of the population in the metabolic studies. This work aims to review the existing literature focusing on these three issues and to briefly present our own preliminary experience.}, } @article {pmid35366017, year = {2022}, author = {Nirenberg, MS and Requena, L and Santonja, C and Smith, GT and McClain, SA}, title = {Histopathology of persistent long COVID toe: A case report.}, journal = {Journal of cutaneous pathology}, volume = {49}, number = {9}, pages = {791-794}, pmid = {35366017}, issn = {1600-0560}, mesh = {*COVID-19/complications/pathology ; Chilblains/pathology ; *Cyanosis/complications/pathology ; Humans ; Male ; Middle Aged ; Obesity/complications ; SARS-CoV-2/pathogenicity ; *Thrombosis/complications/pathology ; Time Factors ; *Toes/pathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within 10 days of exposure. Biopsy specimen of the distal toe 16 weeks after initial exposure showed papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy specimen of "long COVID toe" following presumed SARS-CoV-2 exposure, with a demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.}, } @article {pmid35365631, year = {2022}, author = {Rutkai, I and Mayer, MG and Hellmers, LM and Ning, B and Huang, Z and Monjure, CJ and Coyne, C and Silvestri, R and Golden, N and Hensley, K and Chandler, K and Lehmicke, G and Bix, GJ and Maness, NJ and Russell-Lodrigue, K and Hu, TY and Roy, CJ and Blair, RV and Bohm, R and Doyle-Meyers, LA and Rappaport, J and Fischer, T}, title = {Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1745}, pmid = {35365631}, issn = {2041-1723}, support = {P51 OD011104/OD/NIH HHS/United States ; }, mesh = {Animals ; Brain ; *COVID-19 ; Endothelial Cells ; Humans ; Primates ; *SARS-CoV-2 ; }, abstract = {Neurological manifestations are a significant complication of coronavirus disease (COVID-19), but underlying mechanisms aren't well understood. The development of animal models that recapitulate the neuropathological findings of autopsied brain tissue from patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are critical for elucidating the neuropathogenesis of infection and disease. Here, we show neuroinflammation, microhemorrhages, brain hypoxia, and neuropathology that is consistent with hypoxic-ischemic injury in SARS-CoV-2 infected non-human primates (NHPs), including evidence of neuron degeneration and apoptosis. Importantly, this is seen among infected animals that do not develop severe respiratory disease, which may provide insight into neurological symptoms associated with "long COVID". Sparse virus is detected in brain endothelial cells but does not associate with the severity of central nervous system (CNS) injury. We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.}, } @article {pmid35365568, year = {2023}, author = {Medeiros, M and Edwards, HA and Baquet, CR}, title = {Research in the USA on COVID-19's long-term effects: measures needed to ensure black, indigenous and Latinx communities are not left behind.}, journal = {Journal of medical ethics}, volume = {49}, number = {2}, pages = {87-91}, pmid = {35365568}, issn = {1473-4257}, mesh = {Humans ; COVID-19/ethnology ; Hispanic or Latino ; *Post-Acute COVID-19 Syndrome/ethnology ; SARS-CoV-2 ; United States/epidemiology ; Vaccination ; Black or African American ; Indigenous Peoples ; *Healthcare Disparities/ethnology ; }, abstract = {The SARS-CoV-2 (COVID-19) pandemic continues to expose underlying inequities in healthcare for black, indigenous and Latinx communities in the USA. The gaps in equitable care for communities of colour transcend the diagnosis, treatment and vaccinations related to COVID-19. We are experiencing a continued gap across racial and socioeconomic lines for those who suffer prolonged effects of COVID-19, also known as 'Long COVID-19'. What we know about the treatment for Long COVID-19 so far is that it is complex, requires a multidisciplinary approach and there is still much research needed to fully understand the effects. In this paper, we discuss pragmatic considerations for including affected communities, relevant stakeholders, and leaders from communities of colour in the planning and implementation of Long COVID-19 research.}, } @article {pmid35365499, year = {2022}, author = {Stephenson, T and Allin, B and Nugawela, MD and Rojas, N and Dalrymple, E and Pinto Pereira, S and Soni, M and Knight, M and Cheung, EY and Heyman, I and , and Shafran, R}, title = {Long COVID (post-COVID-19 condition) in children: a modified Delphi process.}, journal = {Archives of disease in childhood}, volume = {107}, number = {7}, pages = {674-680}, pmid = {35365499}, issn = {1468-2044}, support = {/DH_/Department of Health/United Kingdom ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; *COVID-19/complications/diagnosis/epidemiology ; Child ; Consensus ; Delphi Technique ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: The aim of this study was to derive a research definition for 'Long COVID (post-COVID-19 condition)' in children and young people (CYP) to allow comparisons between research studies.

DESIGN: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group.

SETTING: The study was conducted remotely using online surveys and a virtual consensus meeting.

PARTICIPANTS: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years.

MAIN OUTCOME MEASURES: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting.

RESULTS: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test.

CONCLUSIONS: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO.}, } @article {pmid35362302, year = {2022}, author = {Taskiran-Sag, A and Eroğlu, E and Canlar, Ş and Poyraz, BM and Özülken, K and Mumcuoğlu, T and Numanoğlu, N}, title = {Subacute neurological sequelae in mild COVID-19 outpatients.}, journal = {Tuberkuloz ve toraks}, volume = {70}, number = {1}, pages = {27-36}, doi = {10.5578/tt.20229904}, pmid = {35362302}, issn = {2980-3187}, mesh = {Adult ; *COVID-19/complications ; Headache/complications/etiology ; Humans ; Outpatients ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Neurological aspect of COVID-19 is less understood compared to its respiratory and systemic effects. We aimed to define subacute neurological sequelae in patients who recovered from mild COVID-19.

MATERIALS AND METHODS: This study enrolled long COVID patients who had mild infection, were non-hospitalized, and admitted to our hospital with neurological complaints occurring after COVID-19. The evaluation included detailed history of the symptoms, neurological examination, blood tests and necessary investigations relevant to their personal medical situation, and also a retrospective inquiry about their respiratory and neurological status during the acute phase of infection. Descriptive statistical measures, Chi-square and Student's t-test were utilized.

RESULT: We identified 50 patients (29F/21M) with a mean age of 36.9 ± 1.6 (mean ± SEM). The average time from COVID-19 to admission was 99 days(min-max= 15-247). Most frequent neurological complaints were headache (42%) and cognitive dysfunction (42%). Sleep disturbance (36%), prolonged anosmia (30%), prolonged ageusia (22%), fatigue (22%), and dizziness (8%) followed. Most patients with headache experienced headache also as an acute manifestation of COVID-19 (p= 0.02). Acute-stage sleep disorders were found to be more associated with subacute cognitive symptoms than other central symptoms (p= 0.008). The most common neurological symptom in the acute phase was headache (74%). Six patients, despite the absence of any acute-stage neurological symptoms, presented with emergence of subacute neurological sequela. There were only five patients with pulmonary involvement during the acute stage, who were not different from the rest of the cohort in terms of neurological sequelae. There was no increase of inflammatory markers in the blood tests at the subacute stage, or no association of the symptoms to biochemical parameters.

CONCLUSIONS: This study gives a description of neurological sequelae of mild COVID-19 at the subacute stage, in a relatively young group, and reveals that cognitive disturbances, as well as headache, are quite frequent.}, } @article {pmid35360923, year = {2022}, author = {Buonsenso, D and Espuny Pujol, F and Munblit, D and Pata, D and McFarland, S and Simpson, FK}, title = {Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children.}, journal = {Future microbiology}, volume = {17}, number = {8}, pages = {577-588}, pmid = {35360923}, issn = {1746-0921}, mesh = {*COVID-19 ; Child ; Fatigue/diagnosis ; Humans ; *Mental Health ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {Background: Whether long coronavirus disease pertains to children as well is not yet clear. Methods: The authors performed a survey in children suffering from persistent symptoms since initial infection. A total of 510 children infected between January 2020 and January 2021 were included. Results: Symptoms such as fatigue, headache, muscle and joint pain, rashes and heart palpitations and issues such as lack of concentration and short-term memory problems were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. Conclusion: A better comprehension of long coronavirus disease is urgently needed.}, } @article {pmid35360744, year = {2022}, author = {Hüfner, K and Tymoszuk, P and Ausserhofer, D and Sahanic, S and Pizzini, A and Rass, V and Galffy, M and Böhm, A and Kurz, K and Sonnweber, T and Tancevski, I and Kiechl, S and Huber, A and Plagg, B and Wiedermann, CJ and Bellmann-Weiler, R and Bachler, H and Weiss, G and Piccoliori, G and Helbok, R and Loeffler-Ragg, J and Sperner-Unterweger, B}, title = {Who Is at Risk of Poor Mental Health Following Coronavirus Disease-19 Outpatient Management?.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {792881}, pmid = {35360744}, issn = {2296-858X}, abstract = {BACKGROUND: Coronavirus Disease-19 (COVID-19) convalescents are at risk of developing a de novo mental health disorder or worsening of a pre-existing one. COVID-19 outpatients have been less well characterized than their hospitalized counterparts. The objectives of our study were to identify indicators for poor mental health following COVID-19 outpatient management and to identify high-risk individuals.

METHODS: We conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n = 1,157, Italy/IT: n = 893). Primary endpoints were positive screening for depression and anxiety (Patient Health Questionnaire; PHQ-4) and self-perceived overall mental health (OMH) and quality of life (QoL) rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health and QoL with socio-demographic, COVID-19 course, and recovery variables were assessed by multi-parameter Random Forest and Poisson modeling. Mental health risk subsets were defined by self-organizing maps (SOMs) and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/).

RESULTS: Depression and/or anxiety before infection was reported by 4.6% (IT)/6% (AT) of participants. At a median of 79 days (AT)/96 days (IT) post-COVID-19 onset, 12.4% (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3% (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their OMH (AT: 21.8%, IT: 24.1%) or QoL (AT: 20.3%, IT: 25.9%) as fair or poor. Psychosocial stress, physical performance loss, high numbers of acute and sub-acute COVID-19 complaints, and the presence of acute and sub-acute neurocognitive symptoms (impaired concentration, confusion, and forgetfulness) were the strongest correlates of deteriorating mental health and poor QoL. In clustering analysis, these variables defined subsets with a particularly high propensity of post-COVID-19 mental health impairment and decreased QoL. Pre-existing depression or anxiety (DA) was associated with an increased symptom burden during acute COVID-19 and recovery.

CONCLUSION: Our study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as "red flags" of mental health deterioration, which should prompt general practitioners to identify non-hospitalized COVID-19 patients who may benefit from early psychological and psychiatric intervention.

CLINICAL TRIAL REGISTRATION: [ClinicalTrials.gov], identifier [NCT04661462].}, } @article {pmid35359819, year = {2022}, author = {Cahalan, RM and Meade, C and Mockler, S}, title = {SingStrong-A singing and breathing retraining intervention for respiratory and other common symptoms of long COVID: A pilot study.}, journal = {Canadian journal of respiratory therapy : CJRT = Revue canadienne de la therapie respiratoire : RCTR}, volume = {58}, number = {}, pages = {20-27}, pmid = {35359819}, issn = {1205-9838}, abstract = {BACKGROUND: Management of Long COVID (LC) is hugely challenging for clinicians. This pilot study evaluated a breathing retraining and singing programme (SingStrong for LC) to address common LC symptoms. The study hypothesized that this intervention would improve symptoms impacting disordered breathing and participant wellbeing.

METHODS: The 10-week, bi-weekly online programme was comprised of a 45-min class of mindfulness, breathing retraining, vocal exercises, and singing. Sessions were recorded for non-attenders and conducted by a trained vocal coach experienced in respiratory cohorts. Persons with a confirmed COVID-19 diagnosis and persisting symptoms were invited to participate. Demographic and COVID-19 data were collected, and the DePaul Symptom Questionnaire Short Form (DSQ- SF) and COVID-19 Yorkshire Rehab Screen questionnaires were administered. Post-intervention focus groups were also conducted.

RESULTS: Of 27 (F = 23(85%)) participants recruited, data from 21 who completed at least 10 (50%) classes were analysed. Participants showed significant pre-post-intervention improvements in all breathlessness symptoms (at rest: P < 0.001; dressing: P = 0.01; stairs: P < 0.001), fatigue (P = 0.03), usual activities (P = 0.04), pain/disability (P = 0.03), voice quality (P = 0.01), and communication/cognition (P = 0.04). Pre-post number of instances meeting DSQ-SF criteria for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) decreased by a net of nine cases (14.3%). No association between COVID-19 hospitalisation status and diagnosis of ME/CFS was identified. Qualitative feedback from eight participants was overwhelmingly positive with all reporting improvements in breathing and general well-being.

CONCLUSION: The SingStrong programme shows promise as a viable treatment option for LC sufferers. Future studies are required to further investigate the efficacy of this intervention.}, } @article {pmid35359614, year = {2022}, author = {Nittas, V and Gao, M and West, EA and Ballouz, T and Menges, D and Wulf Hanson, S and Puhan, MA}, title = {Long COVID Through a Public Health Lens: An Umbrella Review.}, journal = {Public health reviews}, volume = {43}, number = {}, pages = {1604501}, pmid = {35359614}, issn = {0301-0422}, abstract = {Objectives: To synthesize existing evidence on prevalence as well as clinical and socio-economic aspects of Long COVID. Methods: An umbrella review of reviews and a targeted evidence synthesis of their primary studies, including searches in four electronic databases, reference lists of included reviews, as well as related article lists of relevant publications. Results: Synthesis included 23 reviews and 102 primary studies. Prevalence estimates ranged from 7.5% to 41% in non-hospitalized adults, 2.3%-53% in mixed adult samples, 37.6% in hospitalized adults, and 2%-3.5% in primarily non-hospitalized children. Preliminary evidence suggests that female sex, age, comorbidities, the severity of acute disease, and obesity are associated with Long COVID. Almost 50% of primary studies reported some degree of Long COVID-related social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. Conclusion: Long COVID will likely have a substantial public health impact. Current evidence is still heterogeneous and incomplete. To fully understand Long COVID, well-designed prospective studies with representative samples will be essential.}, } @article {pmid35359346, year = {2021}, author = {Walia, N and Lat, JO and Tariq, R and Tyagi, S and Qazi, AM and Salari, SW and Jafar, A and Kousar, T and Bieniek, S}, title = {Post-acute sequelae of COVID-19 and the mental health implications.}, journal = {Discoveries (Craiova, Romania)}, volume = {9}, number = {4}, pages = {e140}, pmid = {35359346}, issn = {2359-7232}, abstract = {Post-acute sequelae of COVID-19 (PASC) or more commonly known as Long COVID-19, is the term given to persistent symptoms 12 weeks from the initial presentation of COVID-19 infection. Several multi-organ symptoms have been reported by patients. Some common symptoms include headaches, fatigue, memory impairment and mental health complications such as anxiety and depression. People with previous psychiatric diagnosis are at greater risk of developing longer mental health implications from persistent COVID-19 symptoms. Additionally, healthcare workers are at increased risk of being long haulers leading to burnout and exhaustion. The objective of this review article is to provide comprehensive evidence from existing literature on various symptoms reported by patients experiencing Long COVID-19 and the rate of occurrence of such symptoms in different populations. A long-term disease surveillance is required to further understand the persistent symptoms or the long-term impact of this infection.}, } @article {pmid35356830, year = {2023}, author = {Gosser, R and Anderson, S and Blaszczyk, A and Jen, C and Bhatt, S}, title = {In It for the Long Haul: Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2.}, journal = {Journal of pharmacy practice}, volume = {36}, number = {5}, pages = {1048-1051}, pmid = {35356830}, issn = {1531-1937}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19/complications ; Pandemics ; Quality of Life ; Pharmacists ; }, abstract = {The COVID-19 pandemic has caused immeasurable clinical, economic, and societal challenges for the world since early 2020. Intense focus has been placed on determining evidence-based acute management of patients infected with the SARS-CoV-2 virus, as well as accelerating vaccination efforts for those eligible to receive it. As patients recover from infection, many are left with long-term symptoms, known as "Long COVID" or "Post-Acute Sequelae of COVID19," that challenges the ability to fully recover, return to baseline health status, and regain quality of life. As the most accessible healthcare professional, pharmacists can assist with the management of long COVID as a member of the multidisciplinary team. Pharmacists' medication acumen is beneficial to the management of long COVID symptomatology as more research comes to the forefront of this deadly disease.}, } @article {pmid35355964, year = {2022}, author = {Filippetti, L and Pace, N and Louis, JS and Mandry, D and Goehringer, F and Rocher, MS and Jay, N and Selton-Suty, C and Hossu, G and Huttin, O and Marie, PY}, title = {Long-Lasting Myocardial and Skeletal Muscle Damage Evidenced by Serial CMR During the First Year in COVID-19 Patients From the First Wave.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {831580}, pmid = {35355964}, issn = {2297-055X}, abstract = {INTRODUCTION: This observational CMR study aims to characterize left-ventricular (LV) damage, which may be specifically attributed to COVID-19 and is distant in time from the acute phase, through serial CMR performed during the first year in patients with no prior cardiac disease.

METHODS: This study included consecutive patients without any prior history of cardiac disease but with a peak troponin-Ic > 50 ng/ml at the time of the first COVID-wave. All had a CMR in the first months after the acute phase, and some had an additional CMR at the end of the first year to monitor LV function, remodeling, and abnormalities evocative of myositis and myocarditis - i.e., increased T1/T2 relaxation times, increased extracellular volume (ECV), and delayed contrast enhancement.

RESULTS: Nineteen consecutively admitted COVID-19 patients (17 men, median age 66 [57-71] years) were included. Eight (42%) had hypertension, six (32%) were obese, and 16 (84%) had suffered an acute respiratory distress syndrome. The 1[st] CMR, recorded at a median 3.2 [interquartile range: 2.6-3.9] months from the troponin peak, showed (1) LV concentric remodeling in 12 patients (63%), (2) myocardial tissue abnormalities in 11 (58%), including 9 increased myocardial ECVs, and (3) 14 (74%) increased ECVs from shoulder skeletal muscles. The 2[nd] CMR, obtained at 11.1 [11.0-11.7] months from the troponin peak in 13 patients, showed unchanged LV function and remodeling but a return to normal or below the normal range for all ECVs of the myocardium and skeletal muscles.

CONCLUSION: Many patients with no history of cardiac disease but for whom an increase in blood troponin-Ic ascertained COVID-19 induced myocardial damage exhibited signs of persistent extracellular edema at a median 3-months from the troponin peak, affecting the myocardium and skeletal muscles, which resolved within a one-year time frame. Associations with long-COVID symptoms need to be investigated on a larger scale now.

CLINICAL TRIAL REGISTRATION: NCT04753762 on the ClinicalTrials.gov site.}, } @article {pmid35355961, year = {2022}, author = {Chadda, KR and Blakey, EE and Huang, CL and Jeevaratnam, K}, title = {Long COVID-19 and Postural Orthostatic Tachycardia Syndrome- Is Dysautonomia to Be Blamed?.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {860198}, pmid = {35355961}, issn = {2297-055X}, abstract = {While the increased arrhythmic tendency during acute COVID-19 infection is recognised, the long-term cardiac electrophysiological complications are less well known. There are a high number of patients reporting ongoing symptoms post-infection, termed long COVID. A recent hypothesis is that long COVID symptoms could be attributed to dysautonomia, defined as malfunction of the autonomic nervous system (ANS). The most prevalent cardiovascular dysautonomia amongst young people is postural orthostatic tachycardia syndrome (POTS). Numerous reports have described the development of POTS as part of long COVID. Possible underlying mechanisms, although not mutually exclusive or exhaustive, include hypovolaemia, neurotropism, inflammation and autoimmunity. Treatment options for POTS and other long COVID symptoms are currently limited. Future research studies should aim to elucidate the underlying mechanisms of dysautonomia to enable the development of targeted therapies. Furthermore, it is important to educate healthcare professionals to recognise complications and conditions arising from COVID-19, such as POTS, to allow prompt diagnosis and access to early treatment.}, } @article {pmid35355308, year = {2022}, author = {Díaz-Resendiz, KJG and Benitez-Trinidad, AB and Covantes-Rosales, CE and Toledo-Ibarra, GA and Ortiz-Lazareno, PC and Girón-Pérez, DA and Bueno-Durán, AY and Pérez-Díaz, DA and Barcelos-García, RG and Girón-Pérez, MI}, title = {Loss of mitochondrial membrane potential (ΔΨm) in leucocytes as post-COVID-19 sequelae.}, journal = {Journal of leukocyte biology}, volume = {112}, number = {1}, pages = {23-29}, pmid = {35355308}, issn = {1938-3673}, mesh = {*COVID-19/complications ; Female ; Humans ; Leukocytes ; Male ; Membrane Potential, Mitochondrial ; Mitochondria/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {The mitochondrial membrane potential (ΔΨm) is a parameter often used to determine mitochondrial function; therefore, it can be used to determine the integrity and functionality of cells. A decrement of ΔΨm is implicated in several inflammatory-related pathologies, such phenomena can be related to COVID-19 infection. The present work aimed to compare the ΔΨm in leucocytes (human PBMCs; HPBMC) isolated from healthy control (HC) subjects, patients with COVID-19 (C-19), recovered subjects at 40 ± 13 (R1) and 335 ± 20 (R2) days after infection (dai). Obtained data showed that ΔΨm decreased in HPBMC of subjects with C-19, R1, and R2 compared with HC. When analyzing the ΔΨm data by sex, in females, a significant decrease was observed in R1 and R2 groups versus HC. Regarding men, a significant decrease of ΔΨm was observed in R1, with respect to HC, contrary to R2 group, who reestablished this parameter. Obtained results suggest that the loss of ΔΨm could be related to the long-COVID.}, } @article {pmid35355237, year = {2022}, author = {Loosen, SH and Jensen, BO and Tanislav, C and Luedde, T and Roderburg, C and Kostev, K}, title = {Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients.}, journal = {Infection}, volume = {50}, number = {5}, pages = {1165-1170}, pmid = {35355237}, issn = {1439-0973}, mesh = {Adult ; *COVID-19/complications/epidemiology ; *Coronavirus Infections/diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Lipid Metabolism ; *Lipid Metabolism Disorders/complications ; Male ; Middle Aged ; Obesity/complications/epidemiology ; *Pneumonia, Viral/diagnosis ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development.

METHODS: We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS.

RESULTS: Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28-1.65, p < 0.001) and obesity (OR 1.25, 95% CI 1.08-1.44, p = 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients' age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54-2.13, p < 0.001), female sex (OR 1.33, 95% CI 1.20-1.47, p < 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39-2.00, p < 0.001) and depression (OR 1.27, 95% CI 1.09-1.47, p = < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09-1.95, p = < 0.012) in men were associated with an increased likelihood of developing LCS.

CONCLUSION: Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.}, } @article {pmid35354642, year = {2022}, author = {Houchen-Wolloff, L and Poinasamy, K and Holmes, K and Tarpey, M and Hastie, C and Raihani, K and Rogers, N and Smith, N and Adams, D and Burgess, P and Clark, J and Cranage, C and Desai, M and Geary, N and Gill, R and Mangwani, J and Staunton, L and Berry, C and Bolton, CE and Chalder, T and Chalmers, J and De Soyza, A and Elneima, O and Geddes, J and Heller, S and Ho, LP and Jacob, J and McAuley, H and Parmar, A and Quint, JK and Raman, B and Rowland, M and Singapuri, A and Singh, SJ and Thomas, D and Toshner, MR and Wain, LV and Horsley, AR and Marks, M and Brightling, CE and Evans, RA}, title = {Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19.}, journal = {Thorax}, volume = {77}, number = {7}, pages = {717-720}, pmid = {35354642}, issn = {1468-3296}, support = {MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; CS-2016-16-020/DH_/Department of Health/United Kingdom ; COV0319/DH_/Department of Health/United Kingdom ; 209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Caregivers ; Disease Progression ; Health Priorities ; Humans ; Research Personnel ; Post-Acute COVID-19 Syndrome ; }, abstract = {Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.}, } @article {pmid35354589, year = {2022}, author = {Frésard, I and Genecand, L and Altarelli, M and Gex, G and Vremaroiu, P and Vremaroiu-Coman, A and Lawi, D and Bridevaux, PO}, title = {Dysfunctional breathing diagnosed by cardiopulmonary exercise testing in 'long COVID' patients with persistent dyspnoea.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35354589}, issn = {2052-4439}, mesh = {*COVID-19/complications/diagnosis ; Dyspnea/diagnosis/etiology ; Exercise Test ; Exercise Tolerance/physiology ; Humans ; Male ; Middle Aged ; Respiration ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: 'Long COVID'-associated dyspnoea may persist for months after SARS-CoV-2 infection. Among the causes of persistent dyspnoea, dysfunctional breathing (DB), defined as an erratic or inappropriate ventilation at rest or exercise, has been observed, but little is known about its occurrence and pathophysiology among individuals with 'long COVID'. We aimed to describe the occurrence and identify clinical predictors of DB among patients following SARS-CoV-2 infection.

METHODS: Cardiopulmonary exercise testing (CPET) was performed in 51 SARS-CoV-2 patients (median age, 64 years (IQR, 15)); male, 66.7%) living with 'long COVID' and persistent dyspnoea. CPET was classified into three dominant patterns: respiratory limitation with gas exchange abnormalities (RL); normal CPET or O2 delivery/utilisation impairment (D); and DB. Non-parametric and χ[2] tests were applied to analyse the association between CPET dominant patterns and demographics, pulmonary function tests and SARS-CoV-2 severity.

RESULTS: Among 51 patients, DB mostly without hyperventilation was found in 29.4% (n=15), RL in 54.9% (n=28) and D in 15.7% (n=8). When compared with RL individuals, patients with DB were younger, had significantly less severe initial infection, a better transfer capacity for carbon monoxide (median 85% (IQR, 28)), higher oxygen consumption (22.9 mL/min/kg (IQR, 5.5)), a better ventilatory efficiency slope (31.6 (IQR, 12.8)), and a higher SpO2 (95% (IQR, 3)).

CONCLUSIONS: Our findings suggest that DB without hyperventilation could be an important pathophysiological mechanism of disabling dyspnoea in younger outpatients following SARS-CoV-2 infection, which appears to be a feature of COVID-19 not described in other viral diseases.}, } @article {pmid35351759, year = {2022}, author = {Agarwala, SR and Vijayvargiya, M and Sawant, T}, title = {Secondary osteonecrosis of the knee as a part of long COVID-19 syndrome: a case series.}, journal = {BMJ case reports}, volume = {15}, number = {3}, pages = {}, pmid = {35351759}, issn = {1757-790X}, mesh = {*COVID-19/complications ; Humans ; Knee Joint/diagnostic imaging ; Magnetic Resonance Imaging ; *Osteonecrosis/diagnostic imaging/drug therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 infection affects different organ systems with long-term sequelae, which has been termed as long COVID-19 syndrome. To the best of our knowledge, osteonecrosis of the knee as a part of long COVID-19 syndrome has not been documented. Corticosteroids are being used extensively in moderate and severe cases of COVID-19. We report two cases who developed osteonecrosis of the knee after being treated for COVID-19 infection. In our case series, the mean cumulative dose of prednisolone was 1156.5 mg (900-1413 mg), which is less than the cumulative dose reported in literature for osteonecrosis of the knee. In our case series, the patients developed symptomatic osteonecrosis at a mean interval of 73 days after initiation of steroid therapy, with the earliest presenting at 25 days. Early diagnosis of osteonecrosis of the knee on high clinical suspicion by MRI would help in early intervention with bisphosphonate therapy.}, } @article {pmid35350258, year = {2022}, author = {Staffolani, S and Iencinella, V and Cimatti, M and Tavio, M}, title = {Long COVID-19 syndrome as a fourth phase of SARS-CoV-2 infection.}, journal = {Le infezioni in medicina}, volume = {30}, number = {1}, pages = {22-29}, pmid = {35350258}, issn = {2532-8689}, abstract = {The SARS-CoV-2 pandemic has affected in the last two years a large number of subjects, with a high cost in terms of morbidity and mortality. The scientific community made progress in understanding risk factors, pathophysiology, clinical manifestations, diagnosis and treatment of acute SARS-CoV-2 infection. In the last months, another condition has become evident and caught the attention of the scientific community: the so-called long COVID syndrome. The pathophysiology of this condition is not known, even if some hypothesis have been made but not demonstrated yet. Long COVID is characterized by a very heterogeneous group of subacute and/or chronic symptoms and signs that follow the acute phase of SARS-CoV-2 infection and have a very variable duration. The presence of this syndrome in an individual is not dependent from the severity of the acute SARS-CoV-2 infection. Because of the extreme clinical heterogeneity, and also due to the lack of a shared and specific definition of the disease, it is very difficult to know the real prevalence and incidence of this condition. Some risk factors for the development of the disease have been identified: advanced age, elevated body mass index, comorbidities, specific symptoms of acute COVID-19 (in particular dyspnea), number of symptoms in the acute phase and female sex. The number of individuals affected by long COVID is high, even if it occurs only in a part of the subjects who had COVID-19. Therefore, long COVID constitutes now a major health issue and has to be managed in order to ensure an adequate access to care for all the people that need it. "Post COVID" clinics have been created in various countries, especially in Europe, for the management of people affected by long COVID syndrome. Guidelines have been written to help clinicians. An important role in the management of long COVID patients is played by the general practitioner, directly or indirectly linked to post COVID hospital clinics. The extreme heterogeneity of clinical presentation needs a patient-tailored, multidisciplinary approach. As NHS guidelines say, the three principal of care for long COVID patients are personalized care, multidisciplinary support and rehabilitation. More studies are needed in order to know better the pathophysiology of the disease. It is also necessary to create standardized and shared definitions of the disease, in order to better understand the epidemiology, the diagnostic criteria and to offer the right treatment to all the individuals who need it, without social or economic diffeences.}, } @article {pmid35347854, year = {2022}, author = {Han, JH and Womack, KN and Tenforde, MW and Files, DC and Gibbs, KW and Shapiro, NI and Prekker, ME and Erickson, HL and Steingrub, JS and Qadir, N and Khan, A and Hough, CL and Johnson, NJ and Ely, EW and Rice, TW and Casey, JD and Lindsell, CJ and Gong, MN and Srinivasan, V and Lewis, NM and Patel, MM and Self, WH and , }, title = {Associations between persistent symptoms after mild COVID-19 and long-term health status, quality of life, and psychological distress.}, journal = {Influenza and other respiratory viruses}, volume = {16}, number = {4}, pages = {680-689}, pmid = {35347854}, issn = {1750-2659}, support = {K23 HL153584/HL/NHLBI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; 75D30120C07637/CC/CDC HHS/United States ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; Health Status ; Humans ; Prospective Studies ; *Psychological Distress ; Quality of Life/psychology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: We sought to assess whether persistent COVID-19 symptoms beyond 6 months (Long-COVID) among patients with mild COVID-19 is associated with poorer health status, quality of life, and psychological distress.

METHODS: This was a multicenter prospective cohort study that included adult outpatients with acute COVID-19 from eight sites during 2-week sampling periods from April 1 and July 28, 2020. Participants were contacted 6-11 months after their first positive SARS-CoV-2 to complete a survey, which collected information on the severity of eight COVID-19 symptoms using a 4-point scale ranging from 0 (not present) to 3 (severe) at 1 month before COVID-19 (pre-illness) and at follow-up; the difference for each was calculated as an attributable persistent symptom severity score. A total attributable persistent COVID-19 symptom burden score was calculated by summing the attributable persistent severity scores for all eight symptoms. Outcomes measured at long-term follow-up comprised overall health status (EuroQol visual analogue scale), quality of life (EQ-5D-5L), and psychological distress (Patient Health Questionnaire-4). The association between the total attributable persistent COVID-19 burden score and each outcome was analyzed using multivariable proportional odds regression.

RESULTS: Of the 2092 outpatients with COVID-19, 436 (21%) responded to the survey. The median (IQR) attributable persistent COVID-19 symptom burden score was 2 (0, 4); higher scores were associated with lower overall health status (aOR 0.63; 95% CI: 0.57-0.69), lower quality of life (aOR: 0.65; 95%CI: 0.59-0.72), and higher psychological distress (aOR: 1.40; 95%CI, 1.28-1.54) after adjusting for age, race, ethnicity, education, and income.

CONCLUSIONS: In participants with mild acute COVID-19, the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress.}, } @article {pmid35346138, year = {2022}, author = {Schiavi, M and Fugazzaro, S and Bertolini, A and Denti, M and Mainini, C and Accogli, MA and Bedogni, G and Ghizzoni, D and Esseroukh, O and Gualdi, C and Costi, S}, title = {"Like before, but not exactly": the Qualy-REACT qualitative inquiry into the lived experience of long COVID.}, journal = {BMC public health}, volume = {22}, number = {1}, pages = {599}, pmid = {35346138}, issn = {1471-2458}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pregnancy ; *Pregnancy Complications, Infectious ; Quality-Adjusted Life Years ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) affect millions of individuals worldwide. Rehabilitation interventions could support individuals during the recovery phase of COVID-19, but a comprehensive understanding of this new disease and its associated needs is crucial. This qualitative study investigated the experience of individuals who had been hospitalized for COVID-19, focusing on those needs and difficulties they perceived as most urgent.

METHODS: This naturalistic qualitative study was part of a single-center mix-method cross-sectional study (REACT) conducted in Italy during the first peak of the SARS-CoV-2 pandemic. The qualitative data collection took place through a telephone interview conducted 3 months after hospital discharge. The experience of individuals discharged after hospitalization for COVID-19 was investigated through the main research question - "Tell me, how has it been going since you were discharged?". Two secondary questions investigated symptoms, activities, and participation. Data were recorded and transcribed verbatim within 48 h. An empirical phenomenological approach was used by the researchers, who independently analyzed the data and, through consensus, developed an interpretative model to answer the research question. Translation occurred after data was analyzed.

RESULTS: During the first peak of the COVID-19 pandemic, 784 individuals with COVID-19 were discharged from the hospitals of the Local Health Authority of the Province of Reggio Emilia (Italy); 446 were excluded due to the presence of acute or chronic conditions causing disability other than COVID-19 (n. 339), inability to participate in the study procedures (n. 56), insufficient medical documentation to allow for screening (n. 21), discharge to residential facilities (n. 25), and pregnancy (n. 5). Overall, 150 individuals consented to participate in the REACT study, and 56 individuals (60.7% male, average age 62.8 years ±11.8) were interviewed in June-July 2020, up to data saturation. Persistent symptoms, feelings of isolation, fear and stigma, emotional distress, a fatalistic attitude, and return to (adapted) life course were the key themes that characterized the participants' experience after hospital discharge.

CONCLUSIONS: The experience as narrated by the participants in this study confirms the persistence of symptoms described in PASC and highlights the sense of isolation and psychological distress. These phenomena may trigger a vicious circle, but the participants also reported adaptation processes that allowed them to gradually return to their life course. Whether all individuals are able to rapidly activate these mechanisms and whether rehabilitation can help to break this vicious circle by improving residual symptoms remain to be seen.

TRIAL REGISTRATION: ClinicalTrials.com NCT04438239.}, } @article {pmid35345699, year = {2022}, author = {Mitsikostas, DD and Moka, E and Orrillo, E and Aurilio, C and Vadalouca, A and Paladini, A and Varrassi, G}, title = {Neuropathic Pain in Neurologic Disorders: A Narrative Review.}, journal = {Cureus}, volume = {14}, number = {2}, pages = {e22419}, pmid = {35345699}, issn = {2168-8184}, abstract = {Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host's response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.}, } @article {pmid35341334, year = {2022}, author = {Hunt, J and Blease, C and Geraghty, KJ}, title = {Long Covid at the crossroads: Comparisons and lessons from the treatment of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).}, journal = {Journal of health psychology}, volume = {27}, number = {14}, pages = {3106-3120}, doi = {10.1177/13591053221084494}, pmid = {35341334}, issn = {1461-7277}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Whilst parallels have been drawn between Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), there is a well-documented history of negative stereotyping and marginalisation of patients with ME/CFS. A socio-politically oriented comparison of scientific, clinical and societal responses to Long Covid and ME/CFS is thus important to prevent similar harms arising among Long Covid patients. We identify four reasons for injustices in the treatment of ME/CFS patients, and discuss the risk of Long Covid following a similar trajectory. We conclude with policy and practice recommendations to help prevent such injustices arising again, including consideration of critical reflexivity in medical education.}, } @article {pmid35339673, year = {2022}, author = {Peghin, M and De Martino, M and Palese, A and Gerussi, V and Bontempo, G and Graziano, E and Visintini, E and D'Elia, D and Dellai, F and Marrella, F and Fabris, M and Curcio, F and Sartor, A and Isola, M and Tascini, C}, title = {Post-COVID-19 syndrome and humoral response association after 1 year in vaccinated and unvaccinated patients.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {8}, pages = {1140-1148}, pmid = {35339673}, issn = {1469-0691}, mesh = {Adult ; Antibodies, Viral ; *COVID-19/complications/prevention & control ; COVID-19 Vaccines ; Female ; Humans ; Immunoglobulin G ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: This study aimed to describe the impact of vaccination and the role of humoral responses on post-COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2).

METHODS: This prospective study was conducted through interviews to investigate post-COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March-May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed.

RESULTS: A total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post-COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post-COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR: 1.35; 95% CI, 1.11-1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7-37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4-31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs. 0.9-2500 U/mL; OR: 1.36; 95% CI, 0.62-3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451).

DISCUSSION: The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19.}, } @article {pmid35338366, year = {2022}, author = {Ledford, H}, title = {Can drugs reduce the risk of long COVID? What scientists know so far.}, journal = {Nature}, volume = {604}, number = {7904}, pages = {20-21}, doi = {10.1038/d41586-022-00823-y}, pmid = {35338366}, issn = {1476-4687}, mesh = {*COVID-19/complications ; Humans ; *Physicians ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, } @article {pmid35337143, year = {2022}, author = {Karosanidze, I and Kiladze, U and Kirtadze, N and Giorgadze, M and Amashukeli, N and Parulava, N and Iluridze, N and Kikabidze, N and Gudavadze, N and Gelashvili, L and Koberidze, V and Gigashvili, E and Jajanidze, N and Latsabidze, N and Mamageishvili, N and Shengelia, R and Hovhannisyan, A and Panossian, A}, title = {Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {3}, pages = {}, pmid = {35337143}, issn = {1424-8247}, support = {Nr 2021-2//Swedish Herbal Institute R&D in Vallberga/ ; }, abstract = {Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan[®]/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks. Chisan[®] decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan[®] treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time). However, the significant difference between placebo and Chisan[®] treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan[®] treatment group. Furthermore, a significant difference between the placebo and Chisan[®] treatment was observed for creatinine: Chisan[®] significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan[®]/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.}, } @article {pmid35337044, year = {2022}, author = {Nunhofer, V and Weidner, L and Hoeggerl, AD and Zimmermann, G and Badstuber, N and Grabmer, C and Jungbauer, C and Lindlbauer, N and Held, N and Pascariuc, M and Ortner, T and Rohde, E and Laner-Plamberger, S}, title = {Persistence of Naturally Acquired and Functional SARS-CoV-2 Antibodies in Blood Donors One Year after Infection.}, journal = {Viruses}, volume = {14}, number = {3}, pages = {}, pmid = {35337044}, issn = {1999-4915}, support = {20204-WISS/225/197-2019//Paracelsus Medical University/ ; 20102-F1901166-KZP//Paracelsus Medical University/ ; }, mesh = {Adult ; Antibodies, Viral ; Blood Donors ; *COVID-19 ; Humans ; Immunologic Tests ; *SARS-CoV-2 ; }, abstract = {The developmental course of antibodies produced after a SARS-CoV-2 infection has been insufficiently investigated so far. Therefore, the aim of this study was to investigate the dynamics of SARS-CoV-2 antibody levels against the viral nucleocapsid- and spike-protein among Austrian blood donors as a representative group of a supposedly healthy population within the first year after a SARS-CoV-2 infection. The impact of age, sex, vaccination status, AB0-blood group and awareness about the infection was evaluated. Our study shows that the level of anti-N antibodies is declining, while anti-S antibody levels remain stable. Antibodies detected were functional in vitro. Age, sex and blood group do not influence antibody dynamics. However, blood group AB shows significantly lower antibody levels and in vitro functionality compared to other blood groups. Our data reveal that one out of five individuals was not aware of a previous SARS-CoV-2 infection and that the disease course neither affects the level of antibody production nor the in vitro functionality. We also found that 14% of participants show persisting COVID-19-related symptoms for up to nine months. Our results provide valuable insights into the dynamics of the immune response after a SARS-CoV-2 infection in a representative cohort of adult blood donors in Central Europe.}, } @article {pmid35334595, year = {2022}, author = {Wirth, KJ and Scheibenbogen, C}, title = {Dyspnea in Post-COVID Syndrome following Mild Acute COVID-19 Infections: Potential Causes and Consequences for a Therapeutic Approach.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {3}, pages = {}, pmid = {35334595}, issn = {1648-9144}, mesh = {*COVID-19/complications ; Dyspnea/etiology ; Exercise ; *Fatigue Syndrome, Chronic/etiology/therapy ; Humans ; Sodium ; }, abstract = {Dyspnea, shortness of breath, and chest pain are frequent symptoms of post-COVID syndrome (PCS). These symptoms are unrelated to organ damage in most patients after mild acute COVID infection. Hyperventilation has been identified as a cause of exercise-induced dyspnea in PCS. Since there is a broad overlap in symptomatology with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), causes for dyspnea and potential consequences can be deduced by a stringent application of assumptions made for ME/CFS in our recent review papers. One of the first stimuli of respiration in exercise is caused by metabolic feedback via skeletal muscle afferents. Hyperventilation in PCS, which occurs early on during exercise, can arise from a combined disturbance of a poor skeletal muscle energetic situation and autonomic dysfunction (overshooting respiratory response), both found in ME/CFS. The exaggerated respiratory response aggravating dyspnea does not only limit the ability to exercise but further impairs the muscular energetic situation: one of the buffering mechanisms to respiratory alkalosis is a proton shift from intracellular to extracellular space via the sodium-proton-exchanger subtype 1 (NHE1), thereby loading cells with sodium. This adds to two other sodium loading mechanisms already operative, namely glycolytic metabolism (intracellular acidosis) and impaired Na[+]/K[+]ATPase activity. High intracellular sodium has unfavorable effects on mitochondrial calcium and metabolism via sodium-calcium-exchangers (NCX). Mitochondrial calcium overload by high intracellular sodium reversing the transport mode of NCX to import calcium is a key driver for fatigue and chronification. Prevention of hyperventilation has a therapeutic potential by keeping intracellular sodium below the threshold where calcium overload occurs.}, } @article {pmid35334213, year = {2022}, author = {Menuchin-Lasowski, Y and Schreiber, A and Lecanda, A and Mecate-Zambrano, A and Brunotte, L and Psathaki, OE and Ludwig, S and Rauen, T and Schöler, HR}, title = {SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids.}, journal = {Stem cell reports}, volume = {17}, number = {4}, pages = {789-803}, pmid = {35334213}, issn = {2213-6711}, mesh = {Angiotensin-Converting Enzyme 2 ; *COVID-19/complications ; Humans ; Organoids/metabolism ; Retina ; Retinal Ganglion Cells ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several studies have pointed to retinal involvement in COVID-19, yet many questions remain regarding the ability of SARS-CoV-2 to infect and replicate in retinal cells and its effects on the retina. Here, we have used human pluripotent stem cell-derived retinal organoids to study retinal infection by SARS-CoV-2. Indeed, SARS-CoV-2 can infect and replicate in retinal organoids, as it is shown to infect different retinal lineages, such as retinal ganglion cells and photoreceptors. SARS-CoV-2 infection of retinal organoids also induces the expression of several inflammatory genes, such as interleukin 33, a gene associated with acute COVID-19 and retinal degeneration. Finally, we show that the use of antibodies to block ACE2 significantly reduces SARS-CoV-2 infection of retinal organoids, indicating that SARS-CoV-2 infects retinal cells in an ACE2-dependent manner. These results suggest a retinal involvement in COVID-19 and emphasize the need to monitor retinal pathologies as potential sequelae of "long COVID."}, } @article {pmid35333613, year = {2022}, author = {Pelà, G and Goldoni, M and Solinas, E and Cavalli, C and Tagliaferri, S and Ranzieri, S and Frizzelli, A and Marchi, L and Mori, PA and Majori, M and Aiello, M and Corradi, M and Chetta, A}, title = {Sex-Related Differences in Long-COVID-19 Syndrome.}, journal = {Journal of women's health (2002)}, volume = {31}, number = {5}, pages = {620-630}, doi = {10.1089/jwh.2021.0411}, pmid = {35333613}, issn = {1931-843X}, mesh = {*COVID-19/complications/epidemiology ; Chest Pain/etiology ; Cough/complications ; Dyspnea/etiology ; Fatigue ; Female ; Humans ; Male ; Myalgia/complications/etiology ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Sex Characteristics ; *Sleep Wake Disorders/complications/epidemiology ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Sex differences have been demonstrated in the acute phase of coronavirus disease 2019 (COVID-19). Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance. Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.}, } @article {pmid35333125, year = {2022}, author = {Szolnoky, G and González-Ochoa, AJ}, title = {Sulodexide: A Benefit for Cardiovascular Sequelae of Long COVID Patients?.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {28}, number = {}, pages = {10760296221084300}, pmid = {35333125}, issn = {1938-2723}, mesh = {*COVID-19/complications ; Disease Progression ; Glycosaminoglycans ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, } @article {pmid35332308, year = {2022}, author = {Mohamed, MO and Banerjee, A}, title = {Long COVID and cardiovascular disease: a learning health system approach.}, journal = {Nature reviews. Cardiology}, volume = {19}, number = {5}, pages = {287-288}, pmid = {35332308}, issn = {1759-5010}, mesh = {*COVID-19/complications ; *Cardiovascular Diseases/epidemiology ; *Deep Learning ; Humans ; *Learning Health System ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiovascular disease is both a risk factor and potential outcome of the direct, indirect and long-term effects of COVID-19. A recent analysis in >150,000 survivors of COVID-19 demonstrates an increased 1-year risk of numerous cardiovascular diseases. Preventing and managing this new disease burden presents challenges to health systems and requires a learning health system approach.}, } @article {pmid35331679, year = {2022}, author = {Alharbi, KS and Singh, Y and Hassan Almalki, W and Rawat, S and Afzal, O and Alfawaz Altamimi, AS and Kazmi, I and Al-Abbasi, FA and Alzarea, SI and Singh, SK and Bhatt, S and Chellappan, DK and Dua, K and Gupta, G}, title = {Gut Microbiota Disruption in COVID-19 or Post-COVID Illness Association with severity biomarkers: A Possible Role of Pre / Pro-biotics in manipulating microflora.}, journal = {Chemico-biological interactions}, volume = {358}, number = {}, pages = {109898}, pmid = {35331679}, issn = {1872-7786}, mesh = {Biomarkers ; *COVID-19/complications ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term "post-COVID-19 symptoms" refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.}, } @article {pmid35330108, year = {2022}, author = {Jakubec, P and Fišerová, K and Genzor, S and Kolář, M}, title = {Pulmonary Complications after COVID-19.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {35330108}, issn = {2075-1729}, support = {DRO FNOL 00098892//University Hospital Olomouc/ ; IGA_LF_2022_018//Palacký University Olomouc/ ; AZV NU22-B-112//Czech Health Research Council/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a threat to patients not only because of its acute course, but also because of various complications occurring in the following period, that is, more than 28 days after the onset of acute infection. The present study identified a total of 121 patients hospitalized 29 or more days after the first positive result of a PCR test for SARS-CoV-2, of whom 98 patients were included in the study. Patients were divided into two groups by the time interval between the positive COVID-19 test result and hospitalization date. The time intervals were week 5-11 in an ongoing-COVID group (57.1% of patients) and 12 or more weeks in a post-COVID-group (42.9%). The most frequent reason for hospitalization was respiratory tract infection (58.2%). Pneumonia accounted for 77.2% of these cases. Other reasons for hospitalization were interstitial lung disease (22.4%), pulmonary embolism (8.2%), and sarcoidosis (6.1%). The study group was further divided according to the causes of hospitalization into subgroups with infections and other causes. In the group with infectious diseases, there was a shorter time period between PCR positivity and hospitalization and there were significantly more frequent non-respiratory complications. In the entire sample, the in-hospital mortality was 5.1%.}, } @article {pmid35329867, year = {2022}, author = {Maglietta, G and Diodati, F and Puntoni, M and Lazzarelli, S and Marcomini, B and Patrizi, L and Caminiti, C}, title = {Prognostic Factors for Post-COVID-19 Syndrome: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {11}, number = {6}, pages = {}, pmid = {35329867}, issn = {2077-0383}, abstract = {Evidence shows that a substantial proportion of patients with COVID-19 experiences long-term consequences of the disease, but the predisposing factors are poorly understood. We conducted a systematic review and meta-analysis to identify factors present during COVID-19 hospitalization associated with an increased risk of exhibiting new or persisting symptoms (Post-COVID-19 Syndrome, PCS). MedLine and WebOfScience were last searched on 30 September 2021. We included English language clinical trials and observational studies investigating prognostic factors for PCS in adults previously hospitalized for COVID-19, reporting at least one individual prospective follow-up of minimum 12 weeks. Two authors independently assessed risk of bias, which was judged generally moderate. Risk factors were included in the analysis if their association with PCS was investigated by at least two studies. To summarize the prognostic effect of each factor (or group of factors), odds ratios were estimated using raw data. Overall, 20 articles met the inclusion criteria, involving 13,340 patients. Associations were statistically significant for two factors: female sex with any symptoms (OR 1.52; 95% CI 1.27-1.82), with mental health symptoms (OR 1.67, 95% CI 1.21-2.29) and with fatigue (OR 1.54, 95% CI 1.32-1.79); acute disease severity with respiratory symptoms (OR 1.66, 95% CI 1.03-2.68). The I[2] statistics tests were calculated to quantify the degree of study heterogeneity. This is the first meta-analysis measuring the association between factors present during COVID-19 hospitalization and long-term sequelae. The role of female sex and acute disease severity as independent prognostic factors must be confirmed in robust longitudinal studies with longer follow-up. Identifying populations at greatest risk for PCS can enable the development of targeted prevention and management strategies. Systematic review registration: PROSPERO CRD42021253467.}, } @article {pmid35329428, year = {2022}, author = {Jin, H and Lu, L and Fan, H}, title = {Global Trends and Research Hotspots in Long COVID: A Bibliometric Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329428}, issn = {1660-4601}, support = {2019YFC1606306//National Key Research and Development Program of China/ ; }, mesh = {Bibliometrics ; *COVID-19/complications/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is a condition distinguished by long-term sequelae that occur or persist after the convalescence period of COVID-19. During the COVID-19 pandemic, more and more people who tested positive for SARS-CoV-2 experienced long COVID, which attracted the attention of researchers. This study aims to assess the pattern of long COVID research literature, analyze the research topics, and provide insights on long COVID. In this study, we extracted 784 publications from Scopus in the field of long COVID. According to bibliometric analysis, it is found that: developed countries in Europe and America were in leading positions in terms of paper productivity and citations. The International Journal of Environmental Research and Public Health and the Journal of Clinical Medicine were leading journals in the perspective of publications count, and Nature Medicine had the highest number of citations. Author Greenhalgh T has the highest number of papers and citations. The main research topics were: pathophysiology, symptoms, treatment, and epidemiology. The causes of long COVID may be related to organ injury, inflammation, maladaptation of the angiotensin-converting enzyme 2 (ACE2) pathway, and mental factors. The symptoms are varied, including physical and psychological symptoms. Treatment options vary from person to person. Most patients developed at least one long-term symptom. Finally, we presented some possible research opportunities.}, } @article {pmid35329184, year = {2022}, author = {Neculicioiu, VS and Colosi, IA and Costache, C and Sevastre-Berghian, A and Clichici, S}, title = {Time to Sleep?-A Review of the Impact of the COVID-19 Pandemic on Sleep and Mental Health.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {6}, pages = {}, pmid = {35329184}, issn = {1660-4601}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Communicable Disease Control ; Humans ; Mental Health ; Pandemics ; Sleep/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Sleep is intrinsically tied to mental and overall health. Short sleep duration accompanies the modern lifestyle, possibly reaching epidemic proportions. The pandemic and subsequent lockdowns determined a fundamental shift in the modern lifestyle and had profound effects on sleep and mental health. This paper aims to provide an overview of the relationship between sleep, mental health and COVID-19. Contrasting outcomes on sleep health have been highlighted by most reports during the pandemic in the general population. Consequently, while longer sleep durations have been reported, this change was accompanied by decreases in sleep quality and altered sleep timing. Furthermore, an increased impact of sleep deficiencies and mental health burden was generally reported in health care workers as compared with the adult general population. Although not among the most frequent symptoms during the acute or persistent phase, an increased prevalence of sleep deficiencies has been reported in patients with acute and long COVID. The importance of sleep in immune regulation is well known. Consequently, sleep deficiencies may influence multiple aspects of COVID-19, such as the risk, severity, and prognosis of the infection and even vaccine response.}, } @article {pmid35328506, year = {2022}, author = {Che Mohd Nassir, CMN and Zolkefley, MKI and Ramli, MD and Norman, HH and Abdul Hamid, H and Mustapha, M}, title = {Neuroinflammation and COVID-19 Ischemic Stroke Recovery-Evolving Evidence for the Mediating Roles of the ACE2/Angiotensin-(1-7)/Mas Receptor Axis and NLRP3 Inflammasome.}, journal = {International journal of molecular sciences}, volume = {23}, number = {6}, pages = {}, pmid = {35328506}, issn = {1422-0067}, mesh = {Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/*metabolism ; COVID-19/complications/*metabolism/virology ; Humans ; Inflammasomes/*metabolism ; Ischemic Stroke/complications/*metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neuroinflammatory Diseases/complications/*metabolism ; Peptide Fragments/metabolism ; Proteins/*metabolism ; Proto-Oncogene Mas/metabolism ; SARS-CoV-2/metabolism/physiology ; Signal Transduction ; }, abstract = {Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1-7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang- (1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation.}, } @article {pmid35325625, year = {2022}, author = {Narayan, KMV and Staimez, LR}, title = {Rising diabetes diagnosis in long COVID.}, journal = {The lancet. Diabetes & endocrinology}, volume = {10}, number = {5}, pages = {298-299}, pmid = {35325625}, issn = {2213-8595}, support = {P30 DK111024/DK/NIDDK NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; KL2 TR002381/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19/complications ; *Diabetes Mellitus/diagnosis/epidemiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35325624, year = {2022}, author = {Xie, Y and Al-Aly, Z}, title = {Risks and burdens of incident diabetes in long COVID: a cohort study.}, journal = {The lancet. Diabetes & endocrinology}, volume = {10}, number = {5}, pages = {311-321}, pmid = {35325624}, issn = {2213-8595}, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; *Diabetes Mellitus/epidemiology ; Humans ; Hypoglycemic Agents ; SARS-CoV-2 ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: There is growing evidence suggesting that beyond the acute phase of SARS-CoV-2 infection, people with COVID-19 could experience a wide range of post-acute sequelae, including diabetes. However, the risks and burdens of diabetes in the post-acute phase of the disease have not yet been comprehensively characterised. To address this knowledge gap, we aimed to examine the post-acute risk and burden of incident diabetes in people who survived the first 30 days of SARS-CoV-2 infection.

METHODS: In this cohort study, we used the national databases of the US Department of Veterans Affairs to build a cohort of 181 280 participants who had a positive COVID-19 test between March 1, 2020, and Sept 30, 2021, and survived the first 30 days of COVID-19; a contemporary control (n=4 118 441) that enrolled participants between March 1, 2020, and Sept 30, 2021; and a historical control (n=4 286 911) that enrolled participants between March 1, 2018, and Sept 30, 2019. Both control groups had no evidence of SARS-CoV-2 infection. Participants in all three comparison groups were free of diabetes before cohort entry and were followed up for a median of 352 days (IQR 245-406). We used inverse probability weighted survival analyses, including predefined and algorithmically selected high dimensional variables, to estimate post-acute COVID-19 risks of incident diabetes, antihyperglycaemic use, and a composite of the two outcomes. We reported two measures of risk: hazard ratio (HR) and burden per 1000 people at 12 months.

FINDINGS: In the post-acute phase of the disease, compared with the contemporary control group, people with COVID-19 exhibited an increased risk (HR 1·40, 95% CI 1·36-1·44) and excess burden (13·46, 95% CI 12·11-14·84, per 1000 people at 12 months) of incident diabetes; and an increased risk (1·85, 1·78-1·92) and excess burden (12·35, 11·36-13·38) of incident antihyperglycaemic use. Additionally, analyses to estimate the risk of a composite endpoint of incident diabetes or antihyperglycaemic use yielded a HR of 1·46 (95% CI 1·43-1·50) and an excess burden of 18·03 (95% CI 16·59-19·51) per 1000 people at 12 months. Risks and burdens of post-acute outcomes increased in a graded fashion according to the severity of the acute phase of COVID-19 (whether patients were non-hospitalised, hospitalised, or admitted to intensive care). All the results were consistent in analyses using the historical control as the reference category.

INTERPRETATION: In the post-acute phase, we report increased risks and 12-month burdens of incident diabetes and antihyperglycaemic use in people with COVID-19 compared with a contemporary control group of people who were enrolled during the same period and had not contracted SARS-CoV-2, and a historical control group from a pre-pandemic era. Post-acute COVID-19 care should involve identification and management of diabetes.

FUNDING: US Department of Veterans Affairs and the American Society of Nephrology.}, } @article {pmid35323978, year = {2022}, author = {Mitchell, PD and Olaniyi, J and Buckley, C and Donnelly, SC}, title = {Long COVID syndrome and the lung: how long will it last?.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {115}, number = {6}, pages = {349-350}, pmid = {35323978}, issn = {1460-2393}, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging ; Respiratory Function Tests ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The prevalence and duration of the long-term respiratory complications of COVID-19 infection remains to be elucidated. This short commentary reports on recently published studies in patients post-acute COVID-19 infection in terms of symptom prevalence, physiological and radiological sequela and where only symptoms are present despite investigation. Pulmonary function testing, 6-min walk tests, computed tomography chest and more advanced imaging modalities have been incorporated to reveal the underlying pathophysiology that cause such disabling symptoms in patient with post-acute COVID-9 syndrome (PACS). PACS has a serious impact on people's ability to return to work, affecting the physical, mental, social sphere and with significant healthcare and general economic consequences for them, their families and society.}, } @article {pmid35321473, year = {2022}, author = {Prestes, GDS and Simon, CS and Walz, R and Ritter, C and Dal-Pizzol, F}, title = {Respiratory Outcomes After 6 Months of Hospital Discharge in Patients Affected by COVID-19: A Prospective Cohort.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {795074}, pmid = {35321473}, issn = {2296-858X}, abstract = {BACKGROUND: Considering millions of people affected by Coronavirus disease 2019 (COVID-19), long-lasting sequelae can significantly impact health worldwide. Data from prospective studies in lower-middle-income countries on persistent lung dysfunction secondary to COVID-19 are lacking. This work aims to determine risk factors and the impact of persistent lung dysfunctions in COVID-19 survivors.

METHODS: Observational and prospective cohort of patients admitted to a tertiary hospital from June 2020 to November 2020. Persistence of chest CT scan alterations, desaturation in the six-minute walk test (6MWT), forced expiratory volume in one second (FEV1), lung carbon monoxide diffusion (DLCO), and maximum inspiratory pressure (MIP) were measured 6 months after hospital discharge. Additionally, the Barthel index (BI) and the Modified Medical Research Council (mMRC) Dyspnea Scale were used to determine the impact of lung dysfunction in activities of daily living (ADL).

RESULTS: It was included 44 patients. Sixty percent had persistent lung CT scan abnormalities. From 18 to 43% of patients had at least one pulmonary function dysfunction, a decrease in FEV1 was the least prevalent (18%), and a reduction in DLCO and MIP was the most frequent (43%). In general, female gender, comorbidity index, and age were associated with worse lung function. Additionally, the presence of lung dysfunction could predict worse BI (r-square 0.28) and mMRC (r-square 0.32).

CONCLUSION: Long-term lung dysfunction is relatively common in survivors from severe COVID-19 and impacts negatively on ADL and the intensity of dyspnea, similar to studies in high-income countries.}, } @article {pmid35320385, year = {2022}, author = {Verger, A and Kas, A and Dudouet, P and Goehringer, F and Salmon-Ceron, D and Guedj, E}, title = {Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {49}, number = {9}, pages = {3197-3202}, pmid = {35320385}, issn = {1619-7089}, mesh = {Brain/diagnostic imaging/metabolism ; *COVID-19/complications/diagnostic imaging ; Female ; *Fluorodeoxyglucose F18/metabolism ; Humans ; Middle Aged ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/metabolism ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of [18]F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum.

METHODS: From the beginning of August 2021 to the end of October 2021, the brain [18]F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain [18]F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern.

RESULTS: On the 143 brain [18]F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles.

CONCLUSION: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.}, } @article {pmid35318939, year = {2022}, author = {Scherer, PE and Kirwan, JP and Rosen, CJ}, title = {Post-acute sequelae of COVID-19: A metabolic perspective.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35318939}, issn = {2050-084X}, support = {U54 GM104940/GM/NIGMS NIH HHS/United States ; U54GM11516-05/GM/NIGMS NIH HHS/United States ; }, mesh = {COVID-19/*complications/epidemiology/etiology/metabolism/therapy ; Diabetes Mellitus, Type 2 ; Disease Management ; *Disease Susceptibility ; *Energy Metabolism ; Glucose/metabolism ; Glucose Intolerance ; Humans ; Insulin Resistance ; Islets of Langerhans/metabolism ; Liver/metabolism ; Metabolic Syndrome/epidemiology/etiology/metabolism/therapy ; Risk Assessment ; Risk Factors ; T-Lymphocytes/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 pandemic continues to rage around the world. At the same time, despite strong public health measures and high vaccination rates in some countries, a post-COVID-19 syndrome has emerged which lacks a clear definition, prevalence, or etiology. However, fatigue, dyspnea, brain fog, and lack of smell and/or taste are often characteristic of patients with this syndrome. These are evident more than a month after infection, and are labeled as Post-Acute Sequelae of CoV-2 (PASC) or commonly referred to as long-COVID. Metabolic dysfunction (i.e., obesity, insulin resistance, and diabetes mellitus) is a predisposing risk factor for severe acute COVID-19, and there is emerging evidence that this factor plus a chronic inflammatory state may predispose to PASC. In this article, we explore the potential pathogenic metabolic mechanisms that could underly both severe acute COVID-19 and PASC, and then consider how these might be targeted for future therapeutic approaches.}, } @article {pmid35317885, year = {2022}, author = {Bellanti, JA and Settipane, RA}, title = {Long-COVID and loss of smell: A post-COVID olfactory dysfunction that continues to challenge the allergist/immunologist.}, journal = {Allergy and asthma proceedings}, volume = {43}, number = {2}, pages = {93-95}, pmid = {35317885}, issn = {1539-6304}, mesh = {Allergists ; Anosmia ; *COVID-19/complications ; Humans ; *Olfaction Disorders/etiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35316977, year = {2022}, author = {Hollenberg, MD and Epstein, M}, title = {The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.}, journal = {Kidney international supplements}, volume = {12}, number = {1}, pages = {48-62}, pmid = {35316977}, issn = {2157-1724}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic, causing considerable mortality and morbidity worldwide, has fully engaged the biomedical community in attempts to elucidate the pathophysiology of COVID-19 and develop robust therapeutic strategies. To this end, the predominant research focus has been on the adaptive immune response to COVID-19 infections stimulated by mRNA and protein vaccines and on the duration and persistence of immune protection. In contrast, the role of the innate immune response to the viral challenge has been underrepresented. This overview focuses on the innate immune response to COVID-19 infection, with an emphasis on the roles of extracellular proteases in the tissue microenvironment. Proteinase-mediated signaling caused by enzymes in the extracellular microenvironment occurs upstream of the increased production of inflammatory cytokines that mediate COVID-19 pathology. These enzymes include the coagulation cascade, kinin-generating plasma kallikrein, and the complement system, as well as angiotensin-generating proteinases of the renin-angiotensin system. Furthermore, in the context of several articles in this Supplement elucidating and detailing the trajectory of diverse profibrotic pathways, we extrapolate these insights to explore how fibrosis and profibrotic pathways participate importantly in the pathogenesis of COVID-19. We propose that the lessons garnered from understanding the roles of microenvironment proteinases in triggering the innate immune response to COVID-19 pathology will identify potential therapeutic targets and inform approaches to the clinical management of COVID-19. Furthermore, the information may also provide a template for understanding the determinants of COVID-19-induced tissue fibrosis that may follow resolution of acute infection (so-called "long COVID"), which represents a major new challenge to our healthcare systems.}, } @article {pmid35316904, year = {2022}, author = {Jatczak-Pawlik, I and Lewek, J and Czkwianianc, E and Blomberg, A and Krysiak, N and Zeman, K and Jankowski, P and Banach, M and , }, title = {Biochemical and cardiovascular predictors of PIMS-TS risk in children after COVID-19 recovery: preliminary results of the LATE-COVID-Kids Study.}, journal = {Archives of medical science : AMS}, volume = {18}, number = {2}, pages = {545-552}, pmid = {35316904}, issn = {1734-1922}, abstract = {INTRODUCTION: We aimed to characterize biochemical and cardiovascular predictors of the paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) risk based on the data from the LATE-COVID-Kids study.

METHODS: 148 consecutive COVID-19 convalescents hospitalized for the clinical evaluation after the acute phase of COVID-19 were classified into two groups related to symptoms: 33 children finally diagnosed with PIMS-TS and 115 children without PIMS-TS (control group).

RESULTS: PIMS-TS children were significantly younger (6.79 ±4.57 vs. 9.10 ±4.94 years). After adjustment, in comparison to those without, PIMS-TS children had a higher level of antithrombin III (111 ±9.30 vs. 105 ±11.4), higher heart rate (HR)/min (100 (89.0-111) vs. 90 (79.7-100)) and sinus rhythm (p = 0.03) but lower PQ interval (p = 0.02) on admission to hospital. The lymphocytes (absolute count and percentage) were significantly higher in children with PIMS-TS, and the opposite results were obtained for IgA and neutrophils. Furthermore, children with PIMS-TS had a higher level of thyroid stimulating hormone (2.76 (2.16-4.18) vs. 2.36 (1.73-2.83)) and red cell distribution width (p < 0.005) compared to those without.

CONCLUSIONS: It is the first data on the possible predictors of PIMS-TS risk in the Long-COVID period. These results need to be further validated to next create the PIMS SCORE algorithm, which might enable the effective prediction of children with the risk of PIMS-TS occurrence after COVID-19 recovery.}, } @article {pmid35315447, year = {2022}, author = {Cozzi, G and Iacono, A and Troisi, A and Marchetti, F}, title = {[Mental health and pandemic in children and adolescents: what is likely to label as "long-covid".].}, journal = {Recenti progressi in medicina}, volume = {113}, number = {3}, pages = {172-176}, doi = {10.1701/3761.37482}, pmid = {35315447}, issn = {2038-1840}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Humans ; Mental Health ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-covid is a typical condition of adults with a history of probable or confirmed SARS-CoV-2 infection in the previous 3 months and with symptoms lasting over 2 months not explained by an alternative diagnosis. In pediatric age the lack of significative differences comparing the reported symptoms between seropositive and seronegative suggests that long-covid might be less common than previously thought, emphasizing the impact of pandemic-associated symptoms regarding the well-being and mental health of young adolescents. Many children-adolescents, who have had SARS-CoV-2 infection or not, have a health request to which we must respond with a professional approach aimed at a complex functional rehabilitation. The risk is that the "long-covid" becomes a "long-inattention" on relevant mental health problems.}, } @article {pmid35315087, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Navarro-Pardo, E and Torres-Macho, J and Guijarro, C and Pellicer-Valero, OJ}, title = {Exploring the recovery curve for gastrointestinal symptoms from the acute COVID-19 phase to long-term post-COVID: The LONG-COVID-EXP-CM Multicenter Study.}, journal = {Journal of medical virology}, volume = {94}, number = {7}, pages = {2925-2927}, pmid = {35315087}, issn = {1096-9071}, mesh = {*COVID-19/complications ; *Gastrointestinal Diseases ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35313574, year = {2022}, author = {Wu, Q and Ailshire, J and Crimmins, E}, title = {Long COVID and Symptom Trajectory in a Representative Sample of Americans.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35313574}, issn = {2693-5015}, support = {P30 AG017265/AG/NIA NIH HHS/United States ; U01 AG054580/AG/NIA NIH HHS/United States ; }, abstract = {People who have COVID-19 can experience symptoms for months. Studies on long COVID in the population lack representative samples and longitudinal data focusing on new-onset symptoms occurring with COVID while accounting for pre-infection symptoms. We use a sample representing the U.S. community population from the Understanding America Study COVID-19 Survey, which surveyed around 8,000 respondents bi-weekly from March 2020 to March 2021. Our final sample includes 308 infected individuals who were interviewed one month before, around the time of, and 12 weeks after infection. About 23% of the sample experienced new-onset symptoms during infection which lasted for more than 12 weeks, and thus can be considered as having long COVID. The most common persistent new-onset symptoms among those included in the study were headache (22%), runny or stuffy nose (19%), abdominal discomfort (18%), fatigue (17%), and diarrhea (13%). Long COVID was more likely among obese individuals (OR = 5.44, p < 0.001) and those who experienced hair loss (OR = 6.94, p < 0.05), headache (OR = 3.37, p < 0.05), and sore throat (OR = 3.56, p < 0.05) during infection. Risk was unrelated to age, gender, race/ethnicity, education, current smoking status, or comorbid chronic conditions. This work provides national estimates of long COVID in a representative sample after accounting for pre-infection symptoms.}, } @article {pmid35313532, year = {2022}, author = {Amanatidou, E and Gkiouliava, A and Pella, E and Serafidi, M and Tsilingiris, D and Vallianou, NG and Karampela, I and Dalamaga, M}, title = {Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges.}, journal = {Metabolism open}, volume = {14}, number = {}, pages = {100180}, pmid = {35313532}, issn = {2589-9368}, abstract = {Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions against the global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates of protection against severe disease and mortality. Barely a year after vaccines became available, the Omicron variant and its unprecedented speed of transmission has posed a new challenge. Overall, Omicron presents increased immune escape, transmissibility, and decreased pathogenicity. Vaccines do not offer a full protection against SARS-CoV-2 acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who may in turn spread the virus to others. Breakthrough infections may be causally related to the viral profile (viral variant and load, incubation period, transmissibility, pathogenicity, immune evasion), immunity characteristics (mucosal versus systemic immunity, duration of immunity, etc.), host determinants (age, comorbidities, immune status, immunosuppressive drugs) and vaccination properties (platform, antigen dose, dose number, dose interval, route of administration). Determining the rate of breakthrough infections may be challenging and necessitates the conduction of population-based studies regarding vaccine effectiveness as well as neutralizing antibody testing, a surrogate of immune protection. In this review, we analyze the causes of breakthrough infections, their clinical consequences (severity of infection and transmission), methods of determining their incidence as well as challenges and perspectives. Long COVID as well as multi-inflammatory syndrome in adolescents may be significantly reduced in breakthrough infections. The need for universal pancoranavirus vaccines that would aim at protecting against a plethora of SARS-CoV-2 variants as well as emerging variants is discussed. Finally, novel vaccine strategies, such as nasal vaccines, may confer robust mucosal and systemic protection, reducing efficiently transmission.}, } @article {pmid35309052, year = {2022}, author = {Monaghan, A and Jennings, G and Xue, F and Byrne, L and Duggan, E and Romero-Ortuno, R}, title = {Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {833650}, pmid = {35309052}, issn = {1664-042X}, abstract = {In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres[®] NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HRnadir: 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR = 1.09, 95% CI: 1.01-1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOHAS) orthostatic hypotension, but neither correlated with OIAS. Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OItilt). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOHtilt (2 to HR > 120 bpm), but six did not report OItilt. In conclusion, OIAS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).}, } @article {pmid35308999, year = {2021}, author = {Whitfield, E and Coffey, C and Zhang, H and Shi, T and Wu, X and Li, Q and Wu, H}, title = {Axes of Prognosis: Identifying Subtypes of COVID-19 Outcomes.}, journal = {AMIA ... Annual Symposium proceedings. AMIA Symposium}, volume = {2021}, number = {}, pages = {1198-1207}, pmid = {35308999}, issn = {1942-597X}, support = {MC_PC_18029/MRC_/Medical Research Council/United Kingdom ; MR/S004149/1/MRC_/Medical Research Council/United Kingdom ; MR/S004149/2/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications ; Cluster Analysis ; Cohort Studies ; Humans ; Prognosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is a disease with vast impact, yet much remains unclear about patient outcomes. Most approaches to risk prediction of COVID-19 focus on binary or tertiary severity outcomes, despite the heterogeneity of the disease. In this work, we identify heterogeneous subtypes of COVID-19 outcomes by considering 'axes' of prognosis. We propose two innovative clustering approaches - 'Layered Axes' and 'Prognosis Space' - to apply on patients' outcome data. We then show how these clusters can help predict a patient's deterioration pathway on their hospital admission, using random forest classification. We illustrate this methodology on a cohort from Wuhan in early 2020. We discover interesting subgroups of poor prognosis, particularly within respiratory patients, and predict respiratory subgroup membership with high accuracy. This work could assist clinicians in identifying appropriate treatments at patients' hospital admission. Moreover, our method could be used to explore subtypes of 'long COVID' and other diseases with heterogeneous outcomes.}, } @article {pmid35307746, year = {2022}, author = {Noll, J and Reichert, M and Dietrich, M and Riedel, JG and Hecker, M and Padberg, W and Weigand, MA and Hecker, A}, title = {When to operate after SARS-CoV-2 infection? A review on the recent consensus recommendation of the DGC/BDC and the DGAI/BDA.}, journal = {Langenbeck's archives of surgery}, volume = {407}, number = {4}, pages = {1315-1332}, pmid = {35307746}, issn = {1435-2451}, mesh = {*COVID-19 ; Critical Care ; Elective Surgical Procedures/adverse effects ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Since the eruption of the worldwide SARS-CoV-2 pandemic in late 2019/early 2020, multiple elective surgical interventions were postponed. Through pandemic measures, elective operation capacities were reduced in favour of intensive care treatment for critically ill SARS-CoV-2 patients. Although intermittent low-incidence infection rates allowed an increase in elective surgery, surgeons have to include long-term pulmonary and extrapulmonary complications of SARS-CoV-2 infections (especially "Long Covid") in their perioperative management considerations and risk assessment procedures. This review summarizes recent consensus statements and recommendations regarding the timepoint for surgical intervention after SARS-CoV-2 infection released by respective German societies and professional representatives including DGC/BDC (Germany Society of Surgery/Professional Association of German Surgeons e.V.) and DGAI/BDA (Germany Society of Anesthesiology and Intensive Care Medicine/Professional Association of German Anesthesiologists e.V.) within the scope of the recent literature. The current literature reveals that patients with pre- and perioperative SARS-CoV-2 infection have a dramatically deteriorated postoperative outcome. Thereby, perioperative mortality is mainly caused by pulmonary and thromboembolic complications. Notably, perioperative mortality decreases to normal values over time depending on the duration of SARS-CoV-2 infection.}, } @article {pmid35307048, year = {2022}, author = {Burton, A and Aughterson, H and Fancourt, D and Philip, KEJ}, title = {Factors shaping the mental health and well-being of people experiencing persistent COVID-19 symptoms or 'long COVID': qualitative study.}, journal = {BJPsych open}, volume = {8}, number = {2}, pages = {e72}, pmid = {35307048}, issn = {2056-4724}, support = {/WT_/Wellcome Trust/United Kingdom ; 205407/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Around one in ten people who contract COVID-19 report persistent symptoms or 'long COVID'. Impaired mental health and well-being is commonly reported, including anxiety, depression and reduced quality of life. However, there is limited in-depth research exploring why mental health and well-being are affected in people experiencing long COVID.

AIMS: To explore factors affecting mental health and well-being from the perspective of people with long COVID.

METHOD: Semi-structured qualitative interviews were audio-recorded and transcribed. Data were analysed using reflexive thematic analysis. Twenty-one people with long COVID participated in the study. Participants were eligible if they self-reported a positive swab test/antibody test or one or more commonly reported COVID-19 symptoms at illness onset. and experiences of one or more long COVID symptoms ≥3 weeks following illness onset.

RESULTS: Five themes were identified across participant accounts regarding factors affecting mental health and well-being, including symptoms causing severe disruption to daily life, lack of service and treatment options, uncertainty of illness trajectories, experiences of care and understanding from others and changes to identity.

CONCLUSIONS: People with long COVID experience a range of factors that negatively affect their mental health and well-being. Providing patient-centred health services that integrate rapidly evolving research in this area is important, as are peer support groups and supported approaches to self-management.}, } @article {pmid35304353, year = {2022}, author = {Marchetti, F and Cozzi, G}, title = {Are we mislabelling long covid in children and adolescents?.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o705}, doi = {10.1136/bmj.o705}, pmid = {35304353}, issn = {1756-1833}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35301101, year = {2022}, author = {O'Kelly, B and Vidal, L and Avramovic, G and Broughan, J and Connolly, SP and Cotter, AG and Cullen, W and Glaspy, S and McHugh, T and Woo, J and Lambert, JS}, title = {Assessing the impact of COVID-19 at 1-year using the SF-12 questionnaire: Data from the Anticipate longitudinal cohort study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {118}, number = {}, pages = {236-243}, pmid = {35301101}, issn = {1878-3511}, mesh = {*COVID-19/complications/diagnosis/epidemiology ; Cohort Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Prospective Studies ; Quality of Life ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Few studies to date have explored the health-related quality of life (HRQoL) in patients with long COVID.

METHODS: The Anticipate Study is a prospective single-centre observational cohort study. Hospitalised and nonhospitalised patients were seen at a dedicated post-COVID clinic at a 2-4 month (Timepoint 1) and 7-14 month follow-up (Timepoint 2). The main objectives of this study are to assess the longitudinal impact of COVID-19 in patients using the 12-item Short Form Survey (SF-12) score, a health-related quality of life tool, and to identify predictors of developing post-COVID-19 syndrome (PoCS). In addition, we aimed to describe symptomatology and identify predictors of PoCS at 1-year.

RESULTS: A total of 155 patients were enrolled, 105 (68%) were female aged 43.3 (31-52) years. In total 149 (96%) and 94 (61%) patients completed follow-up at median 96 (76-118) days and 364 (303-398) days. The overall cohort had significantly reduced physical composite score (PCS) of the SF-12 (45.39 [10.58] vs 50 [10], p = 0.02). Participants with PoCS had significantly lower scores than those without symptoms at 1-year follow-up (37.2 [10.4] v 46.1 [10.9] p <0.001), and scores for these patients did not improve over the 2 Timepoints (PCS 34.95 [10.5] - 37.2 [10.4], p = 0.22). Fatigue was the most common symptom. Those with 5 or more symptoms at initial diagnosis had lower PCS and mental composite score (MCS) at 1-year. Predictors of PoCS at 1-year were lower PCS and higher baseline heart rate (HR) at clinic review median 3 months after COVID-19.

CONCLUSION: Patients with PoCS have lower PCS scores during follow-up, which did not significantly improve up to a 1-year follow-up. Lower PCS scores and higher HR at rest can be used in the weeks after COVID-19 can help predict those at risk of PoCS at 1 year.}, } @article {pmid35298894, year = {2022}, author = {Magnúsdóttir, I and Lovik, A and Unnarsdóttir, AB and McCartney, D and Ask, H and Kõiv, K and Christoffersen, LAN and Johnson, SU and Hauksdóttir, A and Fawns-Ritchie, C and Helenius, D and González-Hijón, J and Lu, L and Ebrahimi, OV and Hoffart, A and Porteous, DJ and Fang, F and Jakobsdóttir, J and Lehto, K and Andreassen, OA and Pedersen, OBV and Aspelund, T and Valdimarsdóttir, UA and , }, title = {Acute COVID-19 severity and mental health morbidity trajectories in patient populations of six nations: an observational study.}, journal = {The Lancet. Public health}, volume = {7}, number = {5}, pages = {e406-e416}, pmid = {35298894}, issn = {2468-2667}, support = {/WT_/Wellcome Trust/United Kingdom ; CZD/16/6/CSO_/Chief Scientist Office/United Kingdom ; 216767/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; COVID-19 Testing ; Cross-Sectional Studies ; Follow-Up Studies ; Humans ; Mental Health ; Morbidity ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-term mental and physical health consequences of COVID-19 (long COVID) are a persistent public health concern. Little is still known about the long-term mental health of non-hospitalised patients with COVID-19 with varying illness severities. Our aim was to assess the prevalence of adverse mental health symptoms among individuals diagnosed with COVID-19 in the general population by acute infection severity up to 16 months after diagnosis.

METHODS: This observational follow-up study included seven prospectively planned cohorts across six countries (Denmark, Estonia, Iceland, Norway, Sweden, and the UK). Participants were recruited from March 27, 2020, to Aug 13, 2021. Individuals aged 18 years or older were eligible to participate. In a cross-sectional analysis, we contrasted symptom prevalence of depression, anxiety, COVID-19-related distress, and poor sleep quality (screened with validated mental health instruments) among individuals with and without a diagnosis of COVID-19 at entry, 0-16 months from diagnosis. In a cohort analysis, we further used repeated measures to estimate the change in mental health symptoms before and after COVID-19 diagnosis.

FINDINGS: The analytical cohort consisted of 247 249 individuals, 9979 (4·0%) of whom were diagnosed with COVID-19 during the study period. Mean follow-up was 5·65 months (SD 4·26). Participants diagnosed with COVID-19 presented overall with a higher prevalence of symptoms of depression (prevalence ratio [PR] 1·18 [95% CI 1·03-1·36]) and poorer sleep quality (1·13 [1·03-1·24]) but not symptoms of anxiety (0·97 [0·91-1·03]) or COVID-19-related distress (1·05 [0·93-1·20]) compared with individuals without a COVID-19 diagnosis. Although the prevalence of depression and COVID-19-related distress attenuated with time, individuals diagnosed with COVID-19 but never bedridden due to their illness were consistently at lower risk of depression (PR 0·83 [95% CI 0·75-0·91]) and anxiety (0·77 [0·63-0·94]) than those not diagnosed with COVID-19, whereas patients who were bedridden for more than 7 days were persistently at higher risk of symptoms of depression (PR 1·61 [95% CI 1·27-2·05]) and anxiety (1·43 [1·26-1·63]) than those not diagnosed throughout the study period.

INTERPRETATION: Severe acute COVID-19 illness-indicated by extended time bedridden-is associated with long-term mental morbidity among recovering individuals in the general population. These findings call for increased vigilance of adverse mental health development among patients with a severe acute disease phase of COVID-19.

FUNDING: Nordforsk, Horizon2020, Wellcome Trust, and Estonian Research Council.}, } @article {pmid35296346, year = {2022}, author = {Rojas, M and Rodríguez, Y and Acosta-Ampudia, Y and Monsalve, DM and Zhu, C and Li, QZ and Ramírez-Santana, C and Anaya, JM}, title = {Autoimmunity is a hallmark of post-COVID syndrome.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {129}, pmid = {35296346}, issn = {1479-5876}, support = {ABN011/IV-FBG001//Universidad del Rosario/ ; }, mesh = {Adult ; Antibodies, Viral/blood ; *Autoimmunity ; *COVID-19 ; Humans ; Immunoglobulin M/blood ; Male ; Middle Aged ; SARS-CoV-2 ; }, abstract = {Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.}, } @article {pmid35296042, year = {2022}, author = {Castro, JP and Kierkegaard, M and Zeitelhofer, M}, title = {A Call to Use the Multicomponent Exercise Tai Chi to Improve Recovery From COVID-19 and Long COVID.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {827645}, pmid = {35296042}, issn = {2296-2565}, mesh = {*COVID-19/complications ; Exercise ; Humans ; Quality of Life ; *Tai Ji ; Post-Acute COVID-19 Syndrome ; }, abstract = {Approximately 10% of all COVID patients develop long COVID symptoms, which may persist from 1 month up to longer than 1 year. Long COVID may affect any organ/system and manifest in a broad range of symptoms such as shortness of breath, post-exercise malaise, cognitive decline, chronic fatigue, gastrointestinal disorders, musculoskeletal pain and deterioration of mental health. In this context, health institutions struggle with resources to keep up with the prolonged rehabilitation for the increasing number of individuals affected by long COVID. Tai Chi is a multicomponent rehabilitation approach comprising correct breathing technique, balance and neuromuscular training as well as stress- and emotional management. In addition, practicing Tai Chi elicits the relaxation response and balances the autonomic nervous system thus regulating respiration, heart rate, blood pressure and vitality in general. Moreover, Tai Chi has been shown to increase lung capacity, improve cognitive status and mental health, and thereby even the quality of life in diseases such as chronic obstructive pulmonary disease (COPD). Hence, we advocate Tai Chi as potent and suitable rehabilitation tool for post-COVID-19-affected individuals.}, } @article {pmid35295965, year = {2022}, author = {Becker, J and Papagianni, A and Herrmann, E and Nöller, F and Sommer, C and Rittner, HL}, title = {Transient hypoalgesia after COVID-19 infection.}, journal = {Pain reports}, volume = {7}, number = {2}, pages = {e990}, pmid = {35295965}, issn = {2471-2531}, abstract = {INTRODUCTION: Loss of smell or taste are often-cited complications during COVID-19 disease, but there is no clear evidence for affection of the peripheral nervous system.

METHODS: Here, we report a 48-year-old man presenting with persistent dysgeusia and hypoalgesia of the lower legs, hands, and cheeks after COVID-19 infection in Spring 2020.

RESULTS: Upon clinical examination 7 months after the infection, the patient could not feel pain after pinprick stimuli. Quantitative sensory testing revealed increased thermal detection thresholds at the face but no changes at the foot. Electrical C-fiber stimulation elicited lower pain ratings at the distal leg compared with the proximal leg, but overall higher pain ratings than in healthy control subjects. The axon flare reaction in response to histamine and acetylcholine was almost absent with no pain sensation. Skin punch biopsy revealed a reduced intraepidermal nerve fiber density at the lower leg, and transient receptor potential vanilloid 1 and calcitonin gene-related peptide immunoreactivity were similar to a healthy control. Symptoms and positive tests improved 5 months later.

CONCLUSION: In summary, we describe a case of hypoalgesia after COVID-19 disease. Studies investigating long-COVID syndrome should test not only for painful neuropathic symptoms but also for hypoalgesia, especially in patients with prolonged dysgeusia.}, } @article {pmid35294728, year = {2022}, author = {Garout, MA and Saleh, SAK and Adly, HM and Abdulkhaliq, AA and Khafagy, AA and Abdeltawab, MR and Rabaan, AA and Rodriguez-Morales, AJ and Al-Tawfiq, JA and Alandiyjany, MN}, title = {Post-COVID-19 syndrome: assessment of short- and long-term post-recovery symptoms in recovered cases in Saudi Arabia.}, journal = {Infection}, volume = {50}, number = {6}, pages = {1431-1439}, pmid = {35294728}, issn = {1439-0973}, support = {22 UQU 4240001-DSR-01//Umm Al-Qura University/ ; }, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Saudi Arabia/epidemiology ; Anxiety/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Recent studies investigated the endurance of symptoms and occurrence of complications three months after SARS-CoV-2 infection. This study aims to examine the prevalence, variation, and severity of continual symptoms in the post-COVID-19 using a single-center questionnaire.

METHODS: The questionnaire was distributed among population in Saudi Arabia who recovered from COVID-19 between April 1, 2020 and December 31, 2021.

RESULTS: A total of 744 participants completed the questionnaire, 318 (42.8%) recovered less than 3 months, 75 (10.1%) recovered 3-6 months, while 351 (47.2%) recovered more than 6 months. About half of the participants 353 (47.5%) had incessant symptoms and of those patients, more than half had two or more symptoms. Common symptoms included fatigue 189 (25.4%), headache 118 (15.9%), and myalgia 63 (8.5%). Of the participants, 189 (21.4%) experienced continual symptoms including anxiety in 98 (13.2%) and depression in 70 (9.5%).

CONCLUSION: The current study showed a high proportion of individuals with long-COVID-19 symptoms. Thus, proper assessment of the individuals in the post-recovery period can guide the patients to the relevant clinics for rehabilitation. Moreover, there is a great importance to decrease COVID-19 infection, populations should be targeted to boost vaccine efficiency.}, } @article {pmid35294563, year = {2022}, author = {Hennigs, JK and Oqueka, T and Harbaum, L and Klose, H}, title = {[Organ-specific sequelae of COVID-19 in adults].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {65}, number = {4}, pages = {462-470}, pmid = {35294563}, issn = {1437-1588}, mesh = {Adult ; *COVID-19/complications ; Disease Progression ; Germany ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Organ-specific sequelae after COVID-19 occur frequently and are highly diverse in their features. Sequelae and symptoms persisting for more than four weeks after COVID-19 define the condition "long COVID."Organ-specific sequelae of COVID-19 generally occur more often after severe disease. Yet, duration and intensity of organ-specific sequelae are highly variable. While pulmonary sequelae typically persist after more severe acute disease, COVID-19 sequelae may also develop weeks after infection and can affect any organ. The degree of SARS-CoV‑2 specificity of COVID-19 sequelae, however, remains unclear. Thus, diagnosis and treatment of COVID-19 sequelae represent an interdisciplinary challenge. Diagnostic and therapeutic approaches are guided by type, extent, and cause of the specific sequelae as targeted therapy options for long COVID are lacking.In the present work, we review current knowledge regarding the prevalence/incidence, duration, specificity, type, and extent of organ-specific COVID-19 sequelae and summarize current diagnostic and therapeutic strategies (as of November 2021).}, } @article {pmid35291364, year = {2022}, author = {Zulu, JE and Banda, D and Hines, JZ and Luchembe, M and Sivile, S and Siwingwa, M and Kampamba, D and Zyambo, KD and Chirwa, R and Chirwa, L and Malambo, W and Barradas, D and Sinyange, N and Agolory, S and Mulenga, LB and Fwoloshi, S}, title = {Two-month follow-up of persons with SARS-CoV-2 infection-Zambia, September 2020: a cohort study.}, journal = {The Pan African medical journal}, volume = {41}, number = {}, pages = {26}, pmid = {35291364}, issn = {1937-8688}, mesh = {*COVID-19/diagnosis/epidemiology ; Cohort Studies ; Follow-Up Studies ; Humans ; SARS-CoV-2 ; Zambia/epidemiology ; }, abstract = {INTRODUCTION: COVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms.

METHODS: in September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose polymerase chain reaction (PCR) tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions.

RESULTS: of 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms.

CONCLUSION: a notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ´post-acute COVID-19 clinics´ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.}, } @article {pmid35290729, year = {2022}, author = {Hugon, J and Queneau, M and Sanchez Ortiz, M and Msika, EF and Farid, K and Paquet, C}, title = {Cognitive decline and brainstem hypometabolism in long COVID: A case series.}, journal = {Brain and behavior}, volume = {12}, number = {4}, pages = {e2513}, pmid = {35290729}, issn = {2162-3279}, mesh = {Brain/diagnostic imaging ; Brain Stem/diagnostic imaging ; *COVID-19/complications/diagnostic imaging ; *Cognitive Dysfunction/diagnostic imaging/etiology ; Fluorodeoxyglucose F18 ; Humans ; Positron-Emission Tomography ; Radiopharmaceuticals ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To assess FDG cerebral PET in patients suffering from cognitive impairment linked to Long COVID. The COVID pandemic has affected dozens of millions of people around the world and has resulted in the deaths of more than 3 million people. Following the acute forms, it has been reported sometimes long forms of COVID, with involvements of several organs including the brain. Neurological complications can include cognitive disturbances (brain fog) that are very common and can seriously disturb the life of patients.

METHODS: Fluorodeoxyglucose PETs were performed in 3 patients with cognitive decline following COVID infection.

RESULTS: We report here 3 cases of brain fog with major hypometabolic areas of the pons revealed by the cerebral FDG PET.

CONCLUSION: The dysfunction of the locus coeruleus in these patients could partly explain the cognitive disorders observed. Further studies involving larger cohorts of patients suffering from cognitive dysfunction will be needed to determine if the brainstem is frequently affected in these patients.}, } @article {pmid35289448, year = {2022}, author = {Hale, N and Meit, M and Pettyjohn, S and Wahlquist, A and Loos, M}, title = {The implications of long COVID for rural communities.}, journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association}, volume = {38}, number = {4}, pages = {945-947}, pmid = {35289448}, issn = {1748-0361}, mesh = {*COVID-19/complications/epidemiology ; Humans ; Pandemics ; *Pneumonia, Viral/epidemiology ; Rural Population ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35289272, year = {2022}, author = {Costanza, A and Amerio, A and Aguglia, A and Serafini, G and Amore, M and Hasler, R and Ambrosetti, J and Bondolfi, G and Sampogna, G and Berardelli, I and Fiorillo, A and Pompili, M and Nguyen, KD}, title = {Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: Hypothesis for a nefarious collision?.}, journal = {Neuroscience and biobehavioral reviews}, volume = {136}, number = {}, pages = {104606}, pmid = {35289272}, issn = {1873-7528}, mesh = {*COVID-19/complications ; Humans ; Neuroinflammatory Diseases ; SARS-CoV-2 ; Suicidal Ideation ; *Suicide ; Post-Acute COVID-19 Syndrome ; }, abstract = {Accumulating scientific and clinical evidence highlighted pathological hyperinflammation as a cardinal feature of SARS-CoV-2 infection and acute COVID-19 disease. With the emergence of long COVID-19 syndrome, several chronic health consequences, including neuropsychiatric sequelae, have gained attention from the public and medical communities. Since inflammatory mediators have also been accredited as putative biomarkers of suicidal ideations and behaviors, hyper- and neuroinflammation might share some colliding points, overlapping and being interconnected in the context of COVID-19. This review aims to provide a summary of current knowledge on the molecular and cellular mechanisms of COVID-19-associated hyper/neuroinflammation with focus on their relevance to the inflammatory hypothesis of suicide development. Subsequently, strategies to alleviate COVID-19 hyper/neuroinflammation by immunomodulatory agents (many of which at experimental stages) as well as psychopharmacologic/psychotherapeutic approaches are also mentioned. While suicide risk in COVID-19 survivors - until now little known - needs further analysis through longitudinal studies, current observations and mechanistic postulates warrant additional attention to this possibly emerging mental health concern.}, } @article {pmid35289000, year = {2022}, author = {Muraleedharan, M and Panda, NK and Angrish, P and Arora, K and Patro, SK and Bansal, S and Chakrabarti, A and Rudramurthy, SM and Bakshi, J and Mohindra, S and Gupta, R and Virk, RS and Verma, RK and Ramavat, AS and Nayak, G}, title = {As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic.}, journal = {Mycoses}, volume = {65}, number = {5}, pages = {567-576}, pmid = {35289000}, issn = {1439-0507}, mesh = {*COVID-19/epidemiology ; Cross-Sectional Studies ; Fungi ; Humans ; *Mucormycosis/diagnosis ; Pandemics ; Retrospective Studies ; }, abstract = {BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India.

OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic.

METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed.

RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%).

CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.}, } @article {pmid35287333, year = {2022}, author = {Morrow, AK and Malone, LA and Kokorelis, C and Petracek, LS and Eastin, EF and Lobner, KL and Neuendorff, L and Rowe, PC}, title = {Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS.}, journal = {Current pediatrics reports}, volume = {10}, number = {2}, pages = {31-44}, pmid = {35287333}, issn = {2167-4841}, abstract = {PURPOSE OF REVIEW: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

RECENT FINDINGS: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning. The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

SUMMARY: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments. At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40124-022-00261-4.}, } @article {pmid35285122, year = {2022}, author = {Ferrucci, R and Dini, M and Rosci, C and Capozza, A and Groppo, E and Reitano, MR and Allocco, E and Poletti, B and Brugnera, A and Bai, F and Monti, A and Ticozzi, N and Silani, V and Centanni, S and D'Arminio Monforte, A and Tagliabue, L and Priori, A}, title = {One-year cognitive follow-up of COVID-19 hospitalized patients.}, journal = {European journal of neurology}, volume = {29}, number = {7}, pages = {2006-2014}, pmid = {35285122}, issn = {1468-1331}, mesh = {*COVID-19 ; Cognition ; *Cognition Disorders/psychology ; *Cognitive Dysfunction/epidemiology/etiology ; Follow-Up Studies ; Humans ; Neuropsychological Tests ; }, abstract = {BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables.

METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge.

RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037).

CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.}, } @article {pmid35285072, year = {2022}, author = {Peluso, MJ and Deeks, SG and Mustapic, M and Kapogiannis, D and Henrich, TJ and Lu, S and Goldberg, SA and Hoh, R and Chen, JY and Martinez, EO and Kelly, JD and Martin, JN and Goetzl, EJ}, title = {SARS-CoV-2 and Mitochondrial Proteins in Neural-Derived Exosomes of COVID-19.}, journal = {Annals of neurology}, volume = {91}, number = {6}, pages = {772-781}, pmid = {35285072}, issn = {1531-8249}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Biomarkers ; *COVID-19/complications ; Disease Progression ; *Exosomes/metabolism ; Humans ; Membrane Proteins ; Mitochondrial Proteins ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.

METHODS: SARS-CoV-2 proteins and mitochondrial proteins (MPs) in enriched plasma neuron-derived extracellular vesicles (NDEVs) and astrocyte-derived EVs (ADEVs) were quantified in resolved acute COVID-19 without post-acute sequelae of SARS-CoV-2 (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls.

RESULTS: NDEV and ADEV mean levels of SARS-CoV-2 S1 and nucleocapsid (N) proteins were higher in all PASC sub-groups than controls, but only N levels were higher in PASC with than without NP. Exosome marker CD81-normalized NDEV mean levels of subunit 6 of MP respiratory chain complex I and subunit 10 of complex III, and neuroprotective MPs Humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were decreased significantly in PASC with NP but not in PASC without NP relative to controls. NDEV levels of MPs voltage-dependent anion-selective channel protein 1 (VDAC1) and N-methyl-D-aspartate receptor 1 (NMDAR1) were decreased in PASC without and with NP, whereas those of calcium channel MPs mitochondrial calcium uniporter (MCU), sodium/calcium exchanger (NCLX) and leucine zipper EF-hand containing transmembrane 1 protein (LETM1) were decreased only in PASC with NP. ADEV levels of MCU and NCLX only were increased in PASC without and with NP.

INTERPRETATION: Abnormal NDEV and ADEV levels of SARS-CoV-2 N and S1 protein and MPs correlate with NP and may be biomarkers for long-COVID prognostics and therapeutic trials. ANN NEUROL 2022;91:772-781.}, } @article {pmid35285070, year = {2023}, author = {Cozzi, G and Marchetti, F and Barbi, E}, title = {Clinicians need to be careful that they do not confuse mental health issues and long COVID in children and adolescents.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {112}, number = {2}, pages = {180-182}, pmid = {35285070}, issn = {1651-2227}, mesh = {Adolescent ; Child ; Humans ; *Post-Acute COVID-19 Syndrome ; Mental Health ; *COVID-19 ; }, } @article {pmid35284919, year = {2022}, author = {Crea, F}, title = {European Society of Cardiology guidance for the management of cardiovascular disease during the pandemic and a focus on long COVID.}, journal = {European heart journal}, volume = {43}, number = {11}, pages = {1017-1021}, doi = {10.1093/eurheartj/ehac087}, pmid = {35284919}, issn = {1522-9645}, mesh = {*COVID-19/complications ; *Cardiology ; *Cardiovascular Diseases/epidemiology/therapy ; Humans ; Pandemics/prevention & control ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35283306, year = {2022}, author = {Prendki, V and Tiseo, G and Falcone, M and , }, title = {Caring for older adults during the COVID-19 pandemic.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {6}, pages = {785-791}, pmid = {35283306}, issn = {1469-0691}, mesh = {Aged ; *COVID-19/epidemiology/therapy ; *Frailty/diagnosis/epidemiology ; Humans ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Elderly patients represent a high-risk group with increased risk of death from COVID-19. Despite the number of published studies, several unmet needs in care for older adults exist.

OBJECTIVES: To discuss unmet needs of COVID-19 in this special population.

SOURCES: A literature review for studies on COVID-19 in elderly patients published between December 2019 and November 2021 was performed. Clinical questions were formulated to guide the literature search. The search was conducted in the MEDLINE database, combining specific search terms. Two reviewers independently conducted the search and selected the studies according to the prespecified clinical questions.

CONTENT: Elderly patients with COVID-19 have peculiar characteristics. They may have atypical clinical presentation, with no fever and with delirium or neurological manifestations as the most common signs, with potential delayed diagnosis and increased risk of death. The reported fatality rates among elderly patients with COVID-19 are extremely high. Several factors, including comorbidities, atypical presentation, and exclusion from intensive care unit care, contribute to this excess of mortality. Age alone is frequently used as a key factor to exclude the elderly from intensive care, but there is evidence that frailty rather than age better predicts the risk of poor outcome in this category. Durability of vaccine efficacy in the elderly remains debated, and the need for a third booster dose is becoming increasingly evident. Finally, efforts to care for elderly patients who have survived after acute COVID-19 should be implemented, considering the high rates of long COVID sequelae and the risk of longitudinal functional and cognitive decline.

IMPLICATIONS: We highlight peculiar aspects of COVID-19 in elderly patients and factors contributing to high risk of poor outcome in this category. We also illuminated gaps in current evidence, suggesting future research directions and underlining the need for further studies on the optimal management of elderly patients with COVID-19.}, } @article {pmid35282780, year = {2022}, author = {Ceban, F and Leber, A and Jawad, MY and Yu, M and Lui, LMW and Subramaniapillai, M and Di Vincenzo, JD and Gill, H and Rodrigues, NB and Cao, B and Lee, Y and Lin, K and Mansur, RB and Ho, R and Burke, MJ and Rosenblat, JD and McIntyre, RS}, title = {Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research.}, journal = {Infectious diseases (London, England)}, volume = {54}, number = {7}, pages = {467-477}, pmid = {35282780}, issn = {2374-4243}, mesh = {*COVID-19/complications ; Humans ; Research Design ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021-2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.

METHODS: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.

RESULTS: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.

CONCLUSIONS: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.}, } @article {pmid35281581, year = {2022}, author = {Hamazaki, K and Nishigaki, T and Kuramoto, N and Oh, K and Konishi, H}, title = {Secondary Adrenal Insufficiency After COVID-19 Diagnosed by Insulin Tolerance Test and Corticotropin-Releasing Hormone Test.}, journal = {Cureus}, volume = {14}, number = {3}, pages = {e23021}, pmid = {35281581}, issn = {2168-8184}, abstract = {Coronavirus disease 2019 (COVID-19) can affect multiple organs and systems, including the endocrine system. Its symptoms can last for months, resulting in post-COVID-19 conditions, among others. A small number of patients have central adrenal insufficiency (CAI) months after recovery from COVID-19; nevertheless, its pathogenesis has not been fully elucidated. The insulin tolerance test (ITT) is a gold standard test assessing the hypothalamic-pituitary-adrenal axis, and the corticotropin-releasing hormone (CRH) test is useful for differentiating CAI into secondary (pituitary) and tertiary (hypothalamic) adrenal insufficiency. We present a case of new-onset CAI in a young female patient who had no medical history other than COVID-19. Adrenocorticotropin hormone and cortisol responded poorly to both insulin-induced hypoglycemia and CRH administration. These findings suggest that the pituitary gland may be the primary site of hypothalamic-pituitary-adrenal dysfunction, although magnetic resonance imaging of the pituitary gland was unremarkable. To our knowledge, this is possibly the first and only case report of new-onset secondary adrenal insufficiency after recovery from COVID-19 in which the ITT and the CRH test were performed and highly suggestive for the pathogenesis of not only post-COVID-19 CAI but also post-COVID-19 conditions.}, } @article {pmid35280890, year = {2022}, author = {Westermeier, F and Lacerda, EM and Scheibenbogen, C and Sepúlveda, N}, title = {Editorial: Current Insights Into Complex Post-infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {862953}, pmid = {35280890}, issn = {2296-858X}, } @article {pmid35280874, year = {2022}, author = {Nguyen, NN and Hoang, VT and Dao, TL and Meddeb, L and Cortaredona, S and Lagier, JC and Million, M and Raoult, D and Gautret, P}, title = {Long-Term Persistence of Olfactory and Gustatory Disorders in COVID-19 Patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {794550}, pmid = {35280874}, issn = {2296-858X}, abstract = {Smell and taste disorders are frequent symptoms during acute COVID-19 and may persist long after the resolution of the initial phase. This study aims to estimate the proportion and risk factors for smell and/or taste disorders at the onset of symptoms and their persistence after more than 6 months of follow-up in COVID-19 patients. We analyzed a prospective cohort of COVID-19 patients admitted to our institute in Marseille, France in early 2020. After being discharged from the hospital, patients with smell and/or taste disorders were contacted for a telephone interview. Logistic regression analysis was performed to determine the risk factors for smell and/or taste disorders. A total of 3,737 patients were included, of whom 1,676 reported smell and/or taste disorders at the onset of symptoms. Taste and/or smell disorders were independently associated with being younger and female, a lower likelihood of suffering from diabetes, cardiovascular diseases and cancer, a longer delay between the onset of symptoms and consultation, and non-severe forms of COVID-19 at admission. Of the 605 patients with smell and/or taste disorders who were followed-up, 154 (25.5%) reported the persistence of symptoms for more than 6 months. At the time of follow-up, being female, having a chronic respiratory disease and using angiotensin-converting enzyme inhibitors (ACEis) were factors independently associated with the persistence of smell and/or taste disorders. In conclusion, the long-term persistence of olfactory and gustative disorders is frequent among COVID-19 patients, notably affecting female patients and patients who suffered from chronic respiratory diseases before infection. The role of ACEis needs to be further evaluated in larger numbers of patients.}, } @article {pmid35277048, year = {2022}, author = {Carr, AC and Gombart, AF}, title = {Multi-Level Immune Support by Vitamins C and D during the SARS-CoV-2 Pandemic.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35277048}, issn = {2072-6643}, mesh = {Ascorbic Acid/therapeutic use ; *COVID-19/complications ; Humans ; Pandemics/prevention & control ; *SARS-CoV-2 ; Vitamins/therapeutic use ; Post-Acute COVID-19 Syndrome ; }, abstract = {Vitamins C and D have well-known immune supportive roles, with deficiencies in both vitamins predisposing to increased risk and severity of respiratory infections. Numerous studies have indicated that administration of these vitamins, particularly to people who are deficient, can decrease the risk and severity of respiratory infections. This has stimulated an interest in the potential efficacy of these vitamins in people with novel coronavirus (SARS-CoV-2) infection and its more severe disease (COVID-19). In this overview, we highlight the current research evidence around the multiple levels of immune support provided by vitamins C and D in the context of general respiratory infections and with a focus on the current SARS-CoV-2 pandemic. These include: prevention of infection; attenuating infection symptoms and severity; adjunctive therapy for severe disease; attenuating ongoing sequelae (long COVID); and immunisation support. Although some of these topics have not yet been investigated in great depth concerning SARS-CoV-2 and COVID-19, extensive research into the role of these vitamins in general respiratory infections has highlighted directions for future research in the current pandemic.}, } @article {pmid35276888, year = {2022}, author = {Marshall, RP and Droste, JN and Giessing, J and Kreider, RB}, title = {Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review.}, journal = {Nutrients}, volume = {14}, number = {3}, pages = {}, pmid = {35276888}, issn = {2072-6643}, mesh = {*Creatine/metabolism/pharmacology/therapeutic use ; Dietary Supplements ; Energy Metabolism ; *Exercise ; Humans ; Mitochondria/metabolism ; }, abstract = {Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.}, } @article {pmid35272932, year = {2022}, author = {Peluso, MJ and Deeks, SG}, title = {Early clues regarding the pathogenesis of long-COVID.}, journal = {Trends in immunology}, volume = {43}, number = {4}, pages = {268-270}, pmid = {35272932}, issn = {1471-4981}, support = {K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including 'long COVID', is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC.}, } @article {pmid35272262, year = {2022}, author = {Soril, LJJ and Damant, RW and Lam, GY and Smith, MP and Weatherald, J and Bourbeau, J and Hernandez, P and Stickland, MK}, title = {The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature.}, journal = {Respiratory medicine}, volume = {195}, number = {}, pages = {106782}, pmid = {35272262}, issn = {1532-3064}, abstract = {BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required.

METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included.

RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.

CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.}, } @article {pmid35271343, year = {2022}, author = {Merad, M and Blish, CA and Sallusto, F and Iwasaki, A}, title = {The immunology and immunopathology of COVID-19.}, journal = {Science (New York, N.Y.)}, volume = {375}, number = {6585}, pages = {1122-1127}, doi = {10.1126/science.abm8108}, pmid = {35271343}, issn = {1095-9203}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adaptive Immunity ; Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/*complications/*immunology/physiopathology/therapy/virology ; Female ; Humans ; Immunity, Innate ; Inflammation ; Male ; Risk Factors ; SARS-CoV-2/*immunology/physiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.}, } @article {pmid35270905, year = {2022}, author = {Xue, F and Monaghan, A and Jennings, G and Byrne, L and Foran, T and Duggan, E and Romero-Ortuno, R}, title = {A Novel Methodology for the Synchronous Collection and Multimodal Visualization of Continuous Neurocardiovascular and Neuromuscular Physiological Data in Adults with Long COVID.}, journal = {Sensors (Basel, Switzerland)}, volume = {22}, number = {5}, pages = {}, pmid = {35270905}, issn = {1424-8220}, support = {20/COV/8493/SFI_/Science Foundation Ireland/Ireland ; 18/FRL/6188/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Adult ; *COVID-19/complications ; *Cardiovascular System ; Humans ; Muscle Contraction ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e., self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. Methods: To conduct such an investigation, a wide range of continuous non-invasive biomedical sensing technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. Results: With the proposed methodology described and exemplified in this paper, we were able to collect relevant physiological data for the assessment of neurocardiovascular and neuromuscular functioning. We were also able to integrate signals from a variety of instruments in a synchronized fashion and visualize the interactions between different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. Conclusions: The proposed methodology can offer an overview of the functioning of the neurocardiovascular and neuromuscular systems in a combined NCVI/NMFI setup and is capable of conducting comparative studies with signals from multiple participants at any given time in the assessment. This could help clinicians and researchers generate and test hypotheses based on the multimodal inspection of raw data in long COVID and other cohorts.}, } @article {pmid35268400, year = {2022}, author = {Sakurada, Y and Sunada, N and Honda, H and Tokumasu, K and Otsuka, Y and Nakano, Y and Hanayama, Y and Furukawa, M and Hagiya, H and Otsuka, F}, title = {Serial Changes of Long COVID Symptoms and Clinical Utility of Serum Antibody Titers for Evaluation of Long COVID.}, journal = {Journal of clinical medicine}, volume = {11}, number = {5}, pages = {}, pmid = {35268400}, issn = {2077-0383}, abstract = {BACKGROUND: Various symptoms persist even after the acute symptoms in about one third of patients with COVID-19. In February 2021, we established an outpatient clinic in a university hospital for patients with long COVID and started medical treatment for sequelae that persisted one month or more after infection.

METHODS: To determine the key factors that affect the onset and clinical course of sequelae, a retrospective analysis was performed at Okayama University Hospital (Japan) between February and July 2021. We focused on changes in the numbers of symptoms and the background of the patients during a three-month period from the first outpatient visit. We also examined the relationship with SARS-CoV-2 antibody titers.

RESULTS: Information was obtained from medical records for 65 patients. The symptoms of sequelae were diverse, with more than 20 types. The most frequent symptoms were general malaise, dysosmia, dysgeusia, sleeplessness, and headache. These symptoms improved in about 60% of the patients after 3 months. Patients who required hospitalization and had a poor condition in the acute phase and patients who received oxygen/dexamethasone therapy had higher antibody titers at the time of consultation. Patients with antibody titers ≥200 U/mL showed significantly fewer improvements in long COVID symptoms in 1 month, but they showed improvements at 3 months after the first visit.

CONCLUSION: Long COVID symptoms were improved at 3 months after the initial visit in more than half of the patients. Serum antibody titers were higher in patients who experienced a severe acute phase, but the serum antibody titers did not seem to be directly related to the long-term persistence of long COVID symptoms.}, } @article {pmid35267974, year = {2022}, author = {Motti, ML and Tafuri, D and Donini, L and Masucci, MT and De Falco, V and Mazzeo, F}, title = {The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19).}, journal = {Nutrients}, volume = {14}, number = {5}, pages = {}, pmid = {35267974}, issn = {2072-6643}, mesh = {*COVID-19/complications/prevention & control ; Humans ; Nutrients ; Pandemics/prevention & control ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., "long COVID", that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.}, } @article {pmid35266533, year = {2022}, author = {Rienks, R and Holdsworth, D and Davos, CH and Halle, M and Bennett, A and Parati, G and Guettler, N and Nicol, ED}, title = {Cardiopulmonary assessment prior to returning to high-hazard occupations post-symptomatic COVID-19 infection: a position statement of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology.}, journal = {European journal of preventive cardiology}, volume = {29}, number = {13}, pages = {1724-1730}, pmid = {35266533}, issn = {2047-4881}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Occupations ; *Cardiology ; *Aviation ; Post-Acute COVID-19 Syndrome ; }, abstract = {This article provides an overview of the recommendations of the Aviation and Occupational Cardiology Task Force of the European Association of Preventive Cardiology on returning individuals to work in high-hazard occupations (such as flying, diving, and workplaces that are remote from healthcare facilities) following symptomatic Coronavirus Disease 2019 (COVID-19) infection. This process requires exclusion of significant underlying cardiopulmonary disease and this consensus statement (from experts across the field) outlines the appropriate screening and investigative processes that should be undertaken. The recommended response is based on simple screening in primary healthcare to determine those at risk, followed by first line investigations, including an exercise capacity assessment, to identify the small proportion of individuals who may have circulatory, pulmonary, or mixed disease. These individuals can then receive more advanced, targeted investigations. This statement provides a pragmatic, evidence-based approach for those (in all occupations) to assess employee health and capacity prior to a return to work following severe disease, or while continuing to experience significant post-COVID-19 symptoms (so-called 'long-COVID' or post-COVID-19 syndrome).}, } @article {pmid35266128, year = {2022}, author = {Wisnivesky, JP and Govindarajulu, U and Bagiella, E and Goswami, R and Kale, M and Campbell, KN and Meliambro, K and Chen, Z and Aberg, JA and Lin, JJ}, title = {Association of Vaccination with the Persistence of Post-COVID Symptoms.}, journal = {Journal of general internal medicine}, volume = {37}, number = {7}, pages = {1748-1753}, pmid = {35266128}, issn = {1525-1497}, mesh = {Anosmia ; *COVID-19/epidemiology/prevention & control ; COVID-19 Vaccines ; Disease Progression ; Humans ; Quality of Life ; *SARS-CoV-2 ; Vaccination ; }, abstract = {BACKGROUND: Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective cohort to assess differences in post-acute sequelae of COVID (PASC) among vaccinated vs. unvaccinated patients.

METHODS: We used data from a cohort of COVID-19 patients enrolled into a prospective registry established at a tertiary care health system in New York City. Participants underwent a baseline evaluation before COVID-19 vaccines were available and were followed 6 months later. We compared unadjusted and propensity score-adjusted baseline to 6-month change for several PASC-related symptoms and measures: anosmia, respiratory (cough, dyspnea, phlegm, wheezing), depression, anxiety, post-traumatic stress disorder (PTSD; COVID-19-related and other trauma), and quality-of-life domains among participants who received vs. those who did not receive COVID-19 vaccination.

RESULTS: The study included 453 COVID-19 patients with PASC, of which 324 (72%) were vaccinated between the baseline and 6-month visit. Unadjusted analyses did not show significant differences in the baseline to 6-month change in anosmia, respiratory symptoms, depression, anxiety, PTSD, or quality of life (p > 0.05 for all comparisons) among vaccinated vs. unvaccinated patients. Similar results were found in propensity-adjusted comparisons and in secondary analyses based on the number of vaccine doses received.

CONCLUSIONS: Our findings suggest that COVID vaccination is not associated with improvement in PASC. Additional studies are needed to better understand the mechanisms underlying PASC and to develop effective treatments.}, } @article {pmid35265728, year = {2022}, author = {Kenny, G and McCann, K and O'Brien, C and Savinelli, S and Tinago, W and Yousif, O and Lambert, JS and O'Broin, C and Feeney, ER and De Barra, E and Doran, P and Mallon, PWG and , }, title = {Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms.}, journal = {Open forum infectious diseases}, volume = {9}, number = {4}, pages = {ofac060}, pmid = {35265728}, issn = {2328-8957}, abstract = {BACKGROUND: We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID.

METHODS: This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters.

RESULTS: Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36-54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2-3] symptoms per individual in cluster 3 vs 6 [IQR, 5-7] and 4 [IQR, 3-5] in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning.

CONCLUSIONS: Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.}, } @article {pmid35264214, year = {2022}, author = {Esposito, S and Principi, N and Azzari, C and Cardinale, F and Di Mauro, G and Galli, L and Gattinara, GC and Fainardi, V and Guarino, A and Lancella, L and Licari, A and Mancino, E and Marseglia, GL and Leonardi, S and Nenna, R and Zampogna, S and Zona, S and Staiano, A and Midulla, F}, title = {Italian intersociety consensus on management of long covid in children.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {42}, pmid = {35264214}, issn = {1824-7288}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Consensus ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/diagnosis/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed.

MAIN FINDINGS: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type.

CONCLUSIONS: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.}, } @article {pmid35264003, year = {2022}, author = {Buonsenso, D and Di Gennaro, L and De Rose, C and Morello, R and D'Ilario, F and Zampino, G and Piazza, M and Boner, AL and Iraci, C and O'Connell, S and Cohen, VB and Esposito, S and Munblit, D and Reena, J and Sigfrid, L and Valentini, P}, title = {Long-term outcomes of pediatric infections: from traditional infectious diseases to long Covid.}, journal = {Future microbiology}, volume = {17}, number = {}, pages = {551-571}, pmid = {35264003}, issn = {1746-0921}, mesh = {*COVID-19/complications ; Child ; *Communicable Diseases ; Humans ; Italy/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long Covid and lessons learnt from a pediatric post-Covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.}, } @article {pmid35260380, year = {2022}, author = {López-Sampalo, A and Bernal-López, MR and Gómez-Huelgas, R}, title = {Persistent COVID-19 syndrome. A narrative review.}, journal = {Revista clinica espanola}, volume = {222}, number = {4}, pages = {241-250}, pmid = {35260380}, issn = {2254-8874}, mesh = {*COVID-19/complications ; Disease Progression ; Female ; Humans ; Middle Aged ; Quality of Life ; SARS-CoV-2 ; Syndrome ; }, abstract = {As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.}, } @article {pmid35259179, year = {2022}, author = {Ziauddeen, N and Gurdasani, D and O'Hara, ME and Hastie, C and Roderick, P and Yao, G and Alwan, NA}, title = {Characteristics and impact of Long Covid: Findings from an online survey.}, journal = {PloS one}, volume = {17}, number = {3}, pages = {e0264331}, pmid = {35259179}, issn = {1932-6203}, support = {MR/S003711/1/MRC_/Medical Research Council/United Kingdom ; MR/S003711/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; COVID-19/complications/pathology/*psychology/virology ; Cluster Analysis ; Cognitive Dysfunction/*etiology ; Cross-Sectional Studies ; Delivery of Health Care ; Dyspnea/*etiology ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/isolation & purification ; Self Report ; Sleep Wake Disorders/*etiology ; Stress, Physiological ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: Long Covid is a public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life.

METHODS: We collected self-reported data through an online survey using convenience non-probability sampling. The survey enrolled adults who reported lab-confirmed (PCR or antibody) or suspected COVID-19 who were not hospitalised in the first two weeks of illness. This analysis was restricted to those with self-reported Long Covid. Univariate comparisons between those with and without confirmed COVID-19 infection were carried out and agglomerative hierarchical clustering was used to identify specific symptom clusters, and their demographic and functional correlates.

RESULTS: We analysed data from 2550 participants with a median duration of illness of 7.6 months (interquartile range (IQR) 7.1-7.9). 26.5% reported lab-confirmation of infection. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cognitive dysfunction and palpitations became more prevalent later in the illness. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress, and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n = 2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n = 305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n = 2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n = 283, 11.2%) exhibiting more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup.

CONCLUSION: This is an exploratory survey of Long Covid characteristics. Whilst this is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions.}, } @article {pmid35258437, year = {2022}, author = {Hodgson, CL and Higgins, AM and Bailey, MJ and Mather, AM and Beach, L and Bellomo, R and Bissett, B and Boden, IJ and Bradley, S and Burrell, A and Cooper, DJ and Fulcher, BJ and Haines, KJ and Hodgson, IT and Hopkins, J and Jones, AYM and Lane, S and Lawrence, D and van der Lee, L and Liacos, J and Linke, NJ and Gomes, LM and Nickels, M and Ntoumenopoulos, G and Myles, PS and Patman, S and Paton, M and Pound, G and Rai, S and Rix, A and Rollinson, TC and Tipping, CJ and Thomas, P and Trapani, T and Udy, AA and Whitehead, C and Anderson, S and Neto, AS and , }, title = {Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non-COVID-19 Critical Illness.}, journal = {American journal of respiratory and critical care medicine}, volume = {205}, number = {10}, pages = {1159-1168}, pmid = {35258437}, issn = {1535-4970}, mesh = {Adult ; Australia/epidemiology ; *COVID-19 ; Critical Illness ; Humans ; Respiration, Artificial ; *SARS-CoV-2 ; Survivors ; }, abstract = {Rationale: The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non-COVID-19 are yet to be established. Objectives: We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non-COVID-19. Methods: We included critically ill patients with COVID-19 and non-COVID-19 from two prospective observational studies. Patients were eligible if they were adult (age ⩾ 8 yr) and received ⩾24 hours of mechanical ventilation. In addition, patients with COVID-19 were eligible with a positive laboratory PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Measurements and Main Results: Demographic, intervention, and hospital outcome data were obtained from electronic medical records. Survivors were contacted by telephone for functional outcomes with trained outcome assessors using the World Health Organization Disability Assessment Schedule 2.0. Between March 6, 2020, and April 21, 2021, 120 critically ill patients with COVID-19, and between August 2017 and January 2019, 199 critically ill patients without COVID-19, fulfilled the inclusion criteria. Patients with COVID-19 were older (median [interquartile range], 62 [55-71] vs. 58 [44-69] yr; P = 0.019) with a lower Acute Physiology and Chronic Health Evaluation II score (17 [13-20] vs. 19 [15-23]; P = 0.011). Although duration of ventilation was longer in patients with COVID-19 than in those without COVID-19 (12 [5-19] vs. 4.8 [2.3-8.8] d; P < 0.001), 180-day mortality was similar between the groups (39/120 [32.5%] vs. 70/199 [35.2%]; P = 0.715). The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P = 0.583). Conclusions: At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non-COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).}, } @article {pmid35257903, year = {2022}, author = {Chan Sui Ko, A and Candellier, A and Mercier, M and Joseph, C and Schmit, JL and Lanoix, JP and Andrejak, C}, title = {Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {118}, number = {}, pages = {220-223}, pmid = {35257903}, issn = {1878-3511}, mesh = {*COVID-19/complications ; Female ; Hospitalization ; Humans ; *Hypertension/epidemiology ; Intensive Care Units ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Post-COVID-19 symptoms experienced by many survivors have a further devastating effect. This study aimed to analyze the risk factors associated with long COVID-19 in a prospective cohort of hospitalized patients including those requiring intensive care unit (ICU) transfer, taking into account objective measures of COVID-19 severity.

METHODS: Hospitalized patients with confirmed COVID-19 were enrolled. A structured follow-up visit was performed 4 months after hospital admission. Multivariable adjusted regression models were used to analyse the association between parameters at the acute phase and persistent symptoms.

RESULTS: A follow-up visit was performed in 316 patients including 115 (36.4%) discharged from the ICU. Mean age was 64.1 years, and 201 patients (58.3%) were men. Female sex (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.17-3.22; P =.01), hypertension (OR, 2.01; 95% CI, 1.22-3.31; P <.01), and the number of initial symptoms (NIS) (OR, 1.35; 95% CI, 1.17-1.54; P <.001) were significantly associated with long COVID-19. Number of persistent symptoms was significantly associated with NIS (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.11-1.22; P <.001), female sex (aIRR, 1.56; 95% CI 1.29-1.87; P <.001), hypertension (aIRR, 1.23; 95% CI, 1.02-1.50; P =.03), and length of stay in hospital (aIRR, 1.01; 95% CI, 1.005-1.017; P <.001).

CONCLUSION: Our study suggested that female sex, hypertension, and NIS had a significant impact on persistent symptoms in hospitalized patients in contrast to severity of acute COVID-19 infection.}, } @article {pmid35256450, year = {2022}, author = {O'Brien, KK and Brown, DA and Bergin, C and Erlandson, KM and Vera, JH and Avery, L and Carusone, SC and Cheung, AM and Goulding, S and Harding, R and McCorkell, L and O'Hara, M and Robinson, L and Thomson, C and Wei, H and St Clair-Sullivan, N and Torres, B and Bannan, C and Roche, N and Stokes, R and Gayle, P and Solomon, P}, title = {Long COVID and episodic disability: advancing the conceptualisation, measurement and knowledge of episodic disability among people living with Long COVID - protocol for a mixed-methods study.}, journal = {BMJ open}, volume = {12}, number = {3}, pages = {e060826}, pmid = {35256450}, issn = {2044-6055}, support = {R01 AG054366/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; *COVID-19/complications ; Concept Formation ; Disability Evaluation ; *HIV Infections/rehabilitation ; Humans ; Psychometrics/methods ; Reproducibility of Results ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: As the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. Our aims are to: (1) characterise disability experiences among people living with Long COVID in Canada, UK, USA and Ireland; and (2) develop a patient-reported outcome measure to assess the presence, severity and episodic nature of disability with Long COVID.

METHODS AND ANALYSIS: In phase 1, we will conduct semistructured interviews with adults living with Long COVID to explore experiences of disability (dimensions, uncertainty, trajectories, influencing contextual factors) and establish an episodic disability (ED) framework in the context of Long COVID (n~10 each country). Using the conceptual framework, we will establish the Long COVID Episodic Disability Questionnaire (EDQ). In phase 2, we will examine the validity (construct, structural) and reliability (internal consistency, test-retest) of the EDQ for use in Long COVID. We will electronically administer the EDQ and four health status criterion measures with adults living with Long COVID, and readminister the EDQ 1 week later (n~170 each country). We will use Rasch analysis to refine the EDQ, and confirm structural and cross-cultural validity. We will calculate Cronbach's alphas (internal consistency reliability), and intraclass correlation coefficients (test-retest reliability), and examine correlations for hypotheses theorising relationships between EDQ and criterion measure scores (construct validity). Using phase 2 data, we will characterise the profile of disability using structural equation modelling techniques to examine relationships between dimensions of disability and the influence of intrinsic and extrinsic contextual factors. This research involves an academic-clinical-community partnership building on foundational work in ED measurement, Long COVID and rehabilitation.

ETHICS AND DISSEMINATION: This study was approved by the University of Toronto Research Ethics Board. Knowledge translation will occur with community collaborators in the form of presentations and publications in open access peer-reviewed journals and presentations.}, } @article {pmid35256357, year = {2022}, author = {Brennan, A and Broughan, J and McCombe, G and Brennan, J and Collins, C and Fawsitt, R and Gallagher, J and Guérandel, A and O'Kelly, B and Quinlan, D and Lambert, JS and Cullen, W}, title = {Enhancing the management of long COVID in general practice: a scoping review.}, journal = {BJGP open}, volume = {6}, number = {3}, pages = {}, pmid = {35256357}, issn = {2398-3795}, abstract = {BACKGROUND: Long COVID is a multifaceted condition, and it has impacted a considerable proportion of those with acute COVID-19. Affected patients often have complex care needs requiring holistic and multidisciplinary care, the kind routinely provided in general practice. However, there is limited evidence regarding GP interventions.

AIM: This study aimed to identify key concepts and knowledge gaps around long COVID by conducting a scoping review of literature on the condition's management by GPs.

DESIGN & SETTING: Arksey and O'Malley's six-stage scoping review framework, with recommendations by Levac et al, was used.

METHOD: PubMed, Google Scholar, the Cochrane Library, Scopus, and Google searches were conducted to identify relevant peer reviewed and grey literature, and study selection process was conducted according to the PRISMA Extension for Scoping Reviews guidelines. Braun and Clarke's 'Thematic Analysis' approach was used to interpret data.

RESULTS: Nineteen of 972 identified articles were selected for review. These included peer reviewed articles and grey literature spanning a wide range of countries. Six themes were identified regarding GP management of long COVID, these being: (1) GP uncertainty, (2) listening and empathy, (3) assessment and monitoring of symptoms, (4) coordinating access to appropriate services, (5) facilitating provision of continual and integrated multidisciplinary care and (6) need to provide or facilitate psychological support.

CONCLUSION: The findings show that GPs can play and have played a key role in the management of long COVID, and that patient care can be improved through better understanding of patient experiences, standardised approaches for symptom identification and treatment, and facilitation of access to multidisciplinary specialist services when needed. Future research evaluating focused GP interventions is needed.}, } @article {pmid35251264, year = {2021}, author = {Maxwell, E and Radford, M}, title = {Long Covid and the ghost of nursing theory.}, journal = {Journal of research in nursing : JRN}, volume = {26}, number = {5}, pages = {362-366}, pmid = {35251264}, issn = {1744-988X}, } @article {pmid35249215, year = {2022}, author = {de Leeuw, E and Yashadhana, A and Hitch, D}, title = {Long COVID: sustained and multiplied disadvantage.}, journal = {The Medical journal of Australia}, volume = {216}, number = {5}, pages = {222-224}, pmid = {35249215}, issn = {1326-5377}, mesh = {COVID-19/*complications/diagnosis/epidemiology/therapy ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35249144, year = {2022}, author = {Cecchetti, G and Agosta, F and Canu, E and Basaia, S and Barbieri, A and Cardamone, R and Bernasconi, MP and Castelnovo, V and Cividini, C and Cursi, M and Vabanesi, M and Impellizzeri, M and Lazzarin, SM and Fanelli, GF and Minicucci, F and Giacalone, G and Falini, A and Falautano, M and Rovere-Querini, P and Roveri, L and Filippi, M}, title = {Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study.}, journal = {Journal of neurology}, volume = {269}, number = {7}, pages = {3400-3412}, pmid = {35249144}, issn = {1432-1459}, mesh = {Adult ; Anosmia ; *COVID-19/complications ; Cognition ; *Cognitive Dysfunction/diagnostic imaging/etiology/pathology ; Dysgeusia ; Electroencephalography ; Humans ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Survivors ; }, abstract = {BACKGROUND AND OBJECTIVES: To explore cognitive, EEG, and MRI features in COVID-19 survivors up to 10 months after hospital discharge.

METHODS: Adult patients with a recent diagnosis of COVID-19 and reporting subsequent cognitive complaints underwent neuropsychological assessment and 19-channel-EEG within 2 months (baseline, N = 49) and 10 months (follow-up, N = 33) after hospital discharge. A brain MRI was obtained for 36 patients at baseline. Matched healthy controls were included. Using eLORETA, EEG regional current densities and linear lagged connectivity values were estimated. Total brain and white matter hyperintensities (WMH) volumes were measured. Clinical and instrumental data were evaluated between patients and controls at baseline, and within patient whole group and with/without dysgeusia/hyposmia subgroups over time. Correlations among findings at each timepoint were computed.

RESULTS: At baseline, 53% and 28% of patients showed cognitive and psychopathological disturbances, respectively, with executive dysfunctions correlating with acute-phase respiratory distress. Compared to healthy controls, patients also showed higher regional current density and connectivity at delta band, correlating with executive performances, and greater WMH load, correlating with verbal memory deficits. A reduction of cognitive impairment and delta band EEG connectivity were observed over time, while psychopathological symptoms persisted. Patients with acute dysgeusia/hyposmia showed lower improvement at memory tests than those without. Lower EEG delta band at baseline predicted worse cognitive functioning at follow-up.

DISCUSSION: COVID-19 patients showed interrelated cognitive, EEG, and MRI abnormalities 2 months after hospital discharge. Cognitive and EEG findings improved at 10 months. Dysgeusia and hyposmia during acute COVID-19 were related with increased vulnerability in memory functions over time.}, } @article {pmid35248780, year = {2022}, author = {Oikonomou, E and Souvaliotis, N and Lampsas, S and Siasos, G and Poulakou, G and Theofilis, P and Papaioannou, TG and Haidich, AB and Tsaousi, G and Ntousopoulos, V and Sakka, V and Charalambous, G and Rapti, V and Raftopoulou, S and Syrigos, K and Tsioufis, C and Tousoulis, D and Vavuranakis, M}, title = {Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study.}, journal = {Vascular pharmacology}, volume = {144}, number = {}, pages = {106975}, pmid = {35248780}, issn = {1879-3649}, mesh = {*COVID-19/complications ; Cohort Studies ; Endothelium, Vascular ; Humans ; Prospective Studies ; Vasodilation/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function.

METHODS: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages.

RESULTS: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge.

CONCLUSION: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.}, } @article {pmid35248142, year = {2022}, author = {Esposito, S and , }, title = {Manifesto of the pediatricians of Emilia-Romagna region, Italy, in favor of vaccination against COVID in children 5-11 years old.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {40}, pmid = {35248142}, issn = {1824-7288}, mesh = {Adult ; *COVID-19/complications/epidemiology/prevention & control ; COVID-19 Vaccines ; Child ; Child, Preschool ; Humans ; Italy/epidemiology ; Pediatricians ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Following the authorization by the regulatory authorities of vaccination against COVID for children aged between 5 and 11, in Emilia-Romagna Region, Italy, the pediatricians of the Italian Society of Pediatrics (SIP), the Italian Society of Neonatology (SIN), the Cultural Association of Pediatrics, the Italian Federation of Pediatricians (FIMP) and the Italian Union of Family Pediatricians (SIMPeF), who work in the hospital and in the territorial setting, have made a univocal and convinced appeal in favor of vaccination also in this age group.

MAIN FINDINGS: In order to contribute to a conscious choice, on the part of parents, based on exhaustive and correct information, a 24-point manifesto was developed. The manifesto showed that vaccines against COVID are the most effective and safest tool we have to counter the spread of SARS-CoV-2 and vaccination against COVID is a right of children just as it is for adults. Children between 5 and 11 years are not protected from the virus and a large part of the newly infected is this age. Although SARS-CoV-2 infection is certainly more benign in children, in some cases it can cause a serious pathology and long COVID. The stress caused by the pandemic, the prolonged closure of schools and the interruption of sports and recreational activities have had a devastating effect on the mental health of children and on the development of their personality. Vaccinating children against COVID serves to protect them from severe forms of disease and long COVID, allowing them to attend school face-to-face and lead a normal social life. The safety of vaccinatin is very high and vaccines against COVID have no influence on fertility nor can they cause developmental or growth side effects.

CONCLUSIONS: The manifesto highlighted that the vaccine against COVID for children aged between 5 and 11 is effective and safe and represents an extraordinary gift for safeguarding health of the younger ones. The invitation, therefore, to parents is to have their children vaccinated against COVID as early as possible.}, } @article {pmid35245941, year = {2022}, author = {Sandmann, FG and Tessier, E and Lacy, J and Kall, M and Van Leeuwen, E and Charlett, A and Eggo, RM and Dabrera, G and Edmunds, WJ and Ramsay, M and Campbell, H and Amirthalingam, G and Jit, M}, title = {Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {1}, pages = {e962-e973}, doi = {10.1093/cid/ciac151}, pmid = {35245941}, issn = {1537-6591}, mesh = {Adult ; *COVID-19 ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prospective Studies ; Quality of Life ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England.

METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls.

RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England.

CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.}, } @article {pmid35242762, year = {2022}, author = {Martínez-Salazar, B and Holwerda, M and Stüdle, C and Piragyte, I and Mercader, N and Engelhardt, B and Rieben, R and Döring, Y}, title = {COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {824851}, pmid = {35242762}, issn = {2296-634X}, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as "Long-COVID-syndrome". Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.}, } @article {pmid35241251, year = {2022}, author = {Mancini, DM and Natelson, BH}, title = {Reply: CPET for Long COVID-19.}, journal = {JACC. Heart failure}, volume = {10}, number = {3}, pages = {215}, pmid = {35241251}, issn = {2213-1787}, mesh = {Bacterial Toxins ; *COVID-19/complications ; Exercise Test ; *Heart Failure ; Humans ; Oxygen Consumption ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35241250, year = {2022}, author = {Naeije, R and Caravita, S}, title = {CPET for Long COVID-19.}, journal = {JACC. Heart failure}, volume = {10}, number = {3}, pages = {214-215}, pmid = {35241250}, issn = {2213-1787}, mesh = {Bacterial Toxins ; *COVID-19/complications ; Exercise Test ; *Heart Failure ; Humans ; Oxygen Consumption ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35239247, year = {2022}, author = {Rass, V and Beer, R and Schiefecker, AJ and Lindner, A and Kofler, M and Ianosi, BA and Mahlknecht, P and Heim, B and Peball, M and Carbone, F and Limmert, V and Kindl, P and Putnina, L and Fava, E and Sahanic, S and Sonnweber, T and Löscher, WN and Wanschitz, JV and Zamarian, L and Djamshidian, A and Tancevski, I and Weiss, G and Bellmann-Weiler, R and Kiechl, S and Seppi, K and Loeffler-Ragg, J and Pfausler, B and Helbok, R}, title = {Neurological outcomes 1 year after COVID-19 diagnosis: A prospective longitudinal cohort study.}, journal = {European journal of neurology}, volume = {29}, number = {6}, pages = {1685-1696}, pmid = {35239247}, issn = {1468-1331}, mesh = {Anosmia/diagnosis/etiology ; *COVID-19/complications/diagnosis ; Cohort Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND AND PURPOSE: Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19.

METHODS: A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment < 26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5).

RESULTS: Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test <13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p > 0.05).

CONCLUSION: Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.}, } @article {pmid35239080, year = {2022}, author = {Bouwensch, C and Hahn, V and Boulmé, F}, title = {Analysis of 160 nonhospitalized COVID-19 patients with mild to moderate symptoms from an Austrian general medical practice: from typical disease pattern to unexpected clinical features.}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {172}, number = {9-10}, pages = {198-210}, pmid = {35239080}, issn = {1563-258X}, mesh = {Austria ; *COVID-19/diagnosis/epidemiology ; COVID-19 Testing ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Patients from the general practice who had severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection between January 2020 and March 2021 participated in an online survey to report their symptoms. This observational study describes the broad range of mild to moderate symptoms experienced by 160 symptom-based coronavirus disease 2019 (COVID-19) nonhospitalized patients, including 89 laboratory-confirmed cases. Compared to confirmed cases, a higher number of presumed and suspected patients had sore throat, shortness of breath, tightness in the chest, fatigue, or severe neck tension. Unexpected COVID-19-associated clinical features, such as alteration of blood consistency, hormonal imbalance, increased muscle tone and/or aches of skeletal muscles, joint pain, or dermatological disorders were observed by the participants. In the early period of the pandemic, COVID-19 diagnosis of patients was based on medical symptoms rather than polymerase chain reaction (PCR) or serological testing. These real-world data are essential to understand the pathophysiology of this virus infection and to develop innovative therapeutic approaches.}, } @article {pmid35238626, year = {2022}, author = {Jovanoski, N and Kuznik, A and Becker, U and Hussein, M and Briggs, A}, title = {Cost-effectiveness of casirivimab/imdevimab in patients with COVID-19 in the ambulatory setting.}, journal = {Journal of managed care & specialty pharmacy}, volume = {28}, number = {5}, pages = {555-565}, doi = {10.18553/jmcp.2022.21469}, pmid = {35238626}, issn = {2376-1032}, mesh = {Adult ; Antibodies, Monoclonal, Humanized ; Cost-Benefit Analysis ; Female ; Humans ; Male ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Most patients infected with SARS-CoV-2, resulting in COVID-19, have only mild symptoms that can be managed in an ambulatory setting. However, a significant number of patients develop a more severe form of the disease and require hospital care, with the risk of long-term sequelae or death. Casirivimab/imdevimab is a combination of 2 recombinant human monoclonal antibodies that has been shown to significantly reduce the risk of hospitalization or death in patients with mild to moderate COVID-19 in the ambulatory setting. OBJECTIVE: To establish the cost-effectiveness of casirivimab/imdevimab in ambulatory individuals with COVID-19. METHODS: A cost-effectiveness model was constructed to simulate the natural history of COVID-19 in ambulatory patients and to identify those patients for whom casirivimab/imdevimab may be a cost-effective treatment from a US payer perspective. Patients enter the model in the ambulatory health state and can receive either active treatment with casirivimab/imdevimab or usual care. Patients can either recover from the infection or be hospitalized, from where they can recover from infection or die. Following this acute phase, patients enter a Markov model to estimate lifetime quality-adjusted life years. The model uses the risk of hospitalization in both the active treatment and usual care cohorts, and age- and sex-specific risk of mortality. Other model inputs include hospitalization costs and health-related utilities in the ambulatory acute treatment phase, the hospitalized setting, and the post-acute phase. Accounting for the heterogeneity of risk by age and comorbidities, results are presented separately for various combinations of baseline age and usual care risk in a 7 × 9 matrix. Outcomes related to "long COVID" are assessed in scenario analyses. RESULTS: In the base case, at a willingness-to-pay threshold of $100,000, treatment with casirivimab/imdevimab was found to be cost-effective in most patients, including those older than 40 years of age with a baseline hospitalization risk greater than or equal to 2% and patients aged 20 years with a baseline risk of hospitalization greater than or equal to 4%, whereas for hospitalization risk greater than or equal to 10%, casirivimab/imdevimab is dominant. Casirivimab/imdevimab was not cost-effective in patients aged 20 years with a 3% or lower risk of hospitalization or in patients aged 30 years with a 2% risk. CONCLUSIONS: This economic analysis found that casirivimab/imdevimab is a cost-effective treatment for most ambulatory patients with COVID-19. DISCLOSURES: N. Jovanoski and U. Becker are employees of F Hoffman-La Roche Ltd.; A. Kuznik and M. Hussein are employees of Regeneron Pharmaceuticals Inc. and hold stock and stock options; A. Briggs has provided consultancy to F Hoffman-La Roche Ltd. and has received consultancy fees from Merck and Co., Inc., GlaxoSmithKline plc., and Novartis. This study was funded by Regeneron Pharmaceuticals, Inc.}, } @article {pmid35238053, year = {2022}, author = {Tsuchida, T and Hirose, M and Inoue, Y and Kunishima, H and Otsubo, T and Matsuda, T}, title = {Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID.}, journal = {Journal of medical virology}, volume = {94}, number = {7}, pages = {3416-3420}, pmid = {35238053}, issn = {1096-9071}, mesh = {Antibodies, Viral ; *COVID-19/complications/prevention & control ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14-21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS-CoV-2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre- and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre- and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed.}, } @article {pmid35236727, year = {2022}, author = {McNarry, MA and Berg, RMG and Shelley, J and Hudson, J and Saynor, ZL and Duckers, J and Lewis, K and Davies, GA and Mackintosh, KA}, title = {Inspiratory muscle training enhances recovery post-COVID-19: a randomised controlled trial.}, journal = {The European respiratory journal}, volume = {60}, number = {4}, pages = {}, pmid = {35236727}, issn = {1399-3003}, mesh = {Adult ; Breathing Exercises ; *COVID-19/complications ; Dyspnea/therapy ; Female ; Humans ; *Lung Diseases, Interstitial ; Male ; Middle Aged ; Muscle Strength ; Quality of Life ; Respiratory Muscles ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT).

METHODS: 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes.

RESULTS: According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness.

CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.}, } @article {pmid35236547, year = {2022}, author = {Förster, C and Colombo, MG and Wetzel, AJ and Martus, P and Joos, S}, title = {Persisting Symptoms After COVID-19.}, journal = {Deutsches Arzteblatt international}, volume = {119}, number = {10}, pages = {167-174}, pmid = {35236547}, issn = {1866-0452}, mesh = {Adult ; *COVID-19/complications/epidemiology ; Fatigue/epidemiology/etiology ; Female ; Hospitalization ; Humans ; Male ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: After recovering from coronavirus disease 2019 (COVID-19), a considerable number of patients report long-term sequelae. The epidemiologic data vary widely in the studies published to date, depending on the study design and the patient cohorts analyzed. Using a population-based approach, we report symptoms and clinical characteristics following COVID-19 (long COVID), focusing on symptoms ≥ 12 weeks (post-COVID-19).

METHODS: In three German administrative districts, all adult patients with a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) between March and September 2020 (n = 4632) were invited to complete a questionnaire. Predictors for post-COVID-19 were identified by multiple ordinal regression analysis. Study registration: DRKS00023069.

RESULTS: A total of 1459 patients were included in the study, 175 (12%) of whom had been hospitalized for treatment of the acute phase of COVID-19. The prevalence of post-COVID-19 was 72.6% (n = 127) and 46.2% (n = 588) for hospitalized and non-hospitalized patients, respectively. The most frequently occurring long-term symptoms were fatigue (41.5% of all symptoms ≥ 12 weeks, n = 297), physical exhaustion (40.8%, n = 292), difficulty in concentrating (30.6%, n = 219), and loss of the senses of taste (25.9%, n = 185) and smell (25.5%, n = 182). Quality of life was significantly impaired in patients with post-COVID-19. The strongest risk factors for post-COVID-19 were female sex, overall severity of comorbidities, and severity of acute COVID-19.

CONCLUSION: Patients who are not hospitalized also frequently experience continued symptoms following COVID-19. The heterogeneity of symptoms calls for a multi - disciplinary stepped-care approach, for which identification of patients at risk is crucial. A limitation of the study is the lack of a control group.}, } @article {pmid35233795, year = {2022}, author = {Giannos, P and Prokopidis, K}, title = {Gut dysbiosis and long COVID-19: Feeling gutted.}, journal = {Journal of medical virology}, volume = {94}, number = {7}, pages = {2917-2918}, pmid = {35233795}, issn = {1096-9071}, mesh = {*COVID-19/complications ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35233035, year = {2022}, author = {Pérez-González, A and Araújo-Ameijeiras, A and Fernández-Villar, A and Crespo, M and Poveda, E and , }, title = {Long COVID in hospitalized and non-hospitalized patients in a large cohort in Northwest Spain, a prospective cohort study.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3369}, pmid = {35233035}, issn = {2045-2322}, support = {CM20/00243//Instituto de Salud Carlos III/ ; COV20/00698//Instituto de Salud Carlos III/ ; COV20/00698//Instituto de Salud Carlos III/ ; }, mesh = {Adult ; Aged ; *COVID-19/epidemiology/therapy ; Female ; Follow-Up Studies ; *Hospitalization ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; *SARS-CoV-2 ; Sex Factors ; Spain/epidemiology ; }, abstract = {Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.}, } @article {pmid35232851, year = {2022}, author = {Saniasiaya, J and Narayanan, P}, title = {Parosmia post COVID-19: an unpleasant manifestation of long COVID syndrome.}, journal = {Postgraduate medical journal}, volume = {98}, number = {e2}, pages = {e96}, doi = {10.1136/postgradmedj-2021-139855}, pmid = {35232851}, issn = {1469-0756}, mesh = {*COVID-19/complications ; Humans ; *Olfaction Disorders ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35232750, year = {2022}, author = {Oaklander, AL and Mills, AJ and Kelley, M and Toran, LS and Smith, B and Dalakas, MC and Nath, A}, title = {Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {9}, number = {3}, pages = {}, pmid = {35232750}, issn = {2332-7812}, support = {R01 NS093653/NS/NINDS NIH HHS/United States ; U01 FD007769/FD/FDA HHS/United States ; }, mesh = {Adrenal Cortex Hormones/*therapeutic use ; Adult ; COVID-19/*complications ; Electrodiagnosis ; Female ; Humans ; Immunoglobulins, Intravenous/*therapeutic use ; Male ; Middle Aged ; Neurologic Examination ; Peripheral Nervous System Diseases/drug therapy/*etiology/physiopathology ; Treatment Outcome ; }, abstract = {BACKGROUND AND OBJECTIVES: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

METHODS: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

RESULTS: Among 17 patients (mean age 43.3 years, 69% female, 94% Caucasian, and 19% Latino), 59% had ≥1 test interpretation confirming neuropathy. These included 63% (10/16) of skin biopsies, 17% (2/12) of electrodiagnostic tests and 50% (4/8) of autonomic function tests. One patient was diagnosed with critical illness axonal neuropathy and another with multifocal demyelinating neuropathy 3 weeks after mild COVID, and ≥10 received small-fiber neuropathy diagnoses. Longitudinal improvement averaged 52%, although none reported complete resolution. For treatment, 65% (11/17) received immunotherapies (corticosteroids and/or IV immunoglobulins).

DISCUSSION: Among evaluated patients with long COVID, prolonged, often disabling, small-fiber neuropathy after mild SARS-CoV-2 was most common, beginning within 1 month of COVID-19 onset. Various evidence suggested infection-triggered immune dysregulation as a common mechanism.}, } @article {pmid35230003, year = {2022}, author = {Banić, M and Janković Makek, M and Samaržija, M and Muršić, D and Boras, Z and Trkeš, V and Baričević, D and Koršić, M and Basara, L and Jalušić Glunčić, T and Vukić Dugac, A}, title = {Risk factors and severity of functional impairment in long COVID: a single-center experience in Croatia.}, journal = {Croatian medical journal}, volume = {63}, number = {1}, pages = {27-35}, pmid = {35230003}, issn = {1332-8166}, mesh = {*COVID-19/complications/epidemiology ; Croatia/epidemiology ; Female ; Humans ; Quality of Life ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIM: To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID.

METHODS: The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS).

RESULTS: The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID.

CONCLUSION: Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.}, } @article {pmid35229544, year = {2022}, author = {Ashton, R and Ansdell, P and Hume, E and Maden-Wilkinson, T and Ryan, D and Tuttiett, E and Faghy, M}, title = {COVID-19 and the long-term cardio-respiratory and metabolic health complications.}, journal = {Reviews in cardiovascular medicine}, volume = {23}, number = {2}, pages = {53}, doi = {10.31083/j.rcm2302053}, pmid = {35229544}, issn = {2153-8174}, mesh = {*COVID-19/complications ; Cardiovascular System ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) transmission continues to impact people globally. Whilst the acute symptoms and management strategies are well documented, millions of people globally are experiencing a prolonged and debilitating symptom profile that is reported to last months and even years. COVID-19 is a multi-system disease however the magnitude of the effects and its associated legacy is presently not well understood. Early reports indicate that multidisciplinary approaches between clinical and non-clinical entities are needed to provide effective and rehabilitative patient support pathways and restore pre-COVID-19 quality of life and functional status. Accordingly, this review provides a summary of the impact on cardiovascular, inflammatory, respiratory, and musculoskeletal function following an acute COVID-19 infection along with the prolonged effects of long-COVID.}, } @article {pmid35229074, year = {2022}, author = {Santarossa, S and Rapp, A and Sardinas, S and Hussein, J and Ramirez, A and Cassidy-Bushrow, AE and Cheng, P and Yu, E}, title = {Understanding the #longCOVID and #longhaulers Conversation on Twitter: Multimethod Study.}, journal = {JMIR infodemiology}, volume = {2}, number = {1}, pages = {e31259}, pmid = {35229074}, issn = {2564-1891}, abstract = {BACKGROUND: The scientific community is just beginning to uncover the potential long-term effects of COVID-19, and one way to start gathering information is by examining the present discourse on the topic. The conversation about long COVID-19 on Twitter provides insight into related public perception and personal experiences.

OBJECTIVE: The aim of this study was to investigate the #longCOVID and #longhaulers conversations on Twitter by examining the combined effects of topic discussion and social network analysis for discovery on long COVID-19.

METHODS: A multipronged approach was used to analyze data (N=2500 records from Twitter) about long COVID-19 and from people experiencing long COVID-19. A text analysis was performed by both human coders and Netlytic, a cloud-based text and social networks analyzer. The social network analysis generated Name and Chain networks that showed connections and interactions between Twitter users.

RESULTS: Among the 2010 tweets about long COVID-19 and 490 tweets by COVID-19 long haulers, 30,923 and 7817 unique words were found, respectively. For both conversation types, "#longcovid" and "covid" were the most frequently mentioned words; however, through visually inspecting the data, words relevant to having long COVID-19 (ie, symptoms, fatigue, pain) were more prominent in tweets by COVID-19 long haulers. When discussing long COVID-19, the most prominent frames were "support" (1090/1931, 56.45%) and "research" (435/1931, 22.53%). In COVID-19 long haulers conversations, "symptoms" (297/483, 61.5%) and "building a community" (152/483, 31.5%) were the most prominent frames. The social network analysis revealed that for both tweets about long COVID-19 and tweets by COVID-19 long haulers, networks are highly decentralized, fragmented, and loosely connected.

CONCLUSIONS: This study provides a glimpse into the ways long COVID-19 is framed by social network users. Understanding these perspectives may help generate future patient-centered research questions.}, } @article {pmid35228971, year = {2022}, author = {Gaur, R and Asthana, S and Yadav, R and Ghuleliya, R and Kumar, D and Akhtar, M and Gonnade, N and Choudhary, A and Mathew, MM and Gaur, N}, title = {Assessment of Physical Disability After Three Months in Patients Recovered From COVID-19: A Cross-Sectional Study.}, journal = {Cureus}, volume = {14}, number = {1}, pages = {e21618}, pmid = {35228971}, issn = {2168-8184}, abstract = {PURPOSE: This study was done to assess the extent of disability in coronavirus disease 2019 (COVID-19) survivors using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

MATERIAL AND METHODS: This was a cross-sectional study with convenient sampling. Institutional ethical clearance was taken. Informed consent was taken from all patients. Disability assessment was done using WHODAS 2.0. All patients were initial reverse transcriptase-polymerase chain reaction (RT-PCR) positive for COVID-19. Patients with neuromuscular deficits or who were taking medication for psychiatric illness before getting infected with COVID-19 were excluded from the study.

RESULTS: Fatigue followed by dyspnea was the most common reported symptom after three months of COVID-19 infection. COVID-19 survivors with fatigue or dyspnea had a more significant disability as compared to other patients. Females had a more significant disability when compared to males. We did not find any significant disability in COVID-19 survivors after three months of disease based on body mass index, hospitalization, diabetes, and oxygen requirements.

CONCLUSION: COVID-19 survivors suffered from significant disability after three months of disease especially females and survivors with fatigue or dyspnea. Recognizing post-COVID-19 sequelae and the availability of rehabilitation services will be critical in preventing another public health crisis after acute COVID-19 infection.}, } @article {pmid35227568, year = {2022}, author = {Serhan, CN and Libreros, S and Nshimiyimana, R}, title = {E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.}, journal = {Seminars in immunology}, volume = {59}, number = {}, pages = {101597}, pmid = {35227568}, issn = {1096-3618}, support = {K99 HL153673/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Humans ; *COVID-19 ; Docosahexaenoic Acids/therapeutic use ; *Eicosapentaenoic Acid/therapeutic use ; Inflammation ; Inflammation Mediators/metabolism ; Metabolome ; Pandemics ; Post-Acute COVID-19 Syndrome ; Clinical Trials as Topic ; }, abstract = {The COVID-19 pandemic has raised international awareness of the importance of rigorous scientific evidence and the havoc caused by uncontrolled excessive inflammation. Here we consider the evidence on whether the specialized pro-resolving mediators (SPMs) are ready to meet this challenge as well as targeted metabololipidomics of the resolution-inflammation metabolomes. Specific stereochemical mechanisms in the biosynthesis of SPMs from omega-3 essential fatty acids give rise to unique local-acting lipid mediators. SPMs possess stereochemically defined potent bioactive structures that are high-affinity ligands for cognate G protein-coupled surface receptors that evoke the cellular responses required for efficient resolution of acute inflammation. The SPMs biosynthesized from the major omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are coined Resolvins (resolution phase interaction products; E series and D-series), Protectins and Maresins (macrophage mediators in resolving inflammation). Their biosynthesis and stereochemical assignments are established and confirmed (>1,441 resolvin publications in PubMed.gov) as well as their functional roles on innate immune cells and adaptive immune cells (both lymphocyte T-cell subsets and B-cells). The resolution of a protective acute inflammatory response is governed mainly by phagocytes that actively clear apoptotic cells, debris, blood clots and pathogens. These resolution phase functions of the acute inflammatory response are enhanced by SPMs, which together prepare the inflammatory loci for homeostasis and stimulate tissue regeneration via activating stem cells and the biosynthesis of novel cys-SPMs (e.g. MCTRs, PCTRs and RCTRs). These cys-SPMs also activate regeneration, are organ protective and stimulate resolution of local inflammation. Herein, we review the biosynthesis and functions of the E-series resolvins, namely resolvin E1 (the first n-3 resolvin identified), resolvin E2, resolvin E3 and resolvin E4 biosynthesized from their precursor eicosapentaenoic acid (EPA), and the critical role of total organic synthesis in confirming SPM complete stereochemistry, establishing their potent functions in resolution of inflammation, and novel structures. The physical properties of each biologically derived SPM, i.e., ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS[2]) fragmentation, were matched to SPMs biosynthesized and prepared by stereospecific total organic synthesis. We briefly review this approach, also used with the endogenous D-series resolvins, protectins and maresins confirming their potent functions in resolution of inflammation, that paves the way for their rigorous evaluation in human tissues and clinical trials. The assignment of complete stereochemistry for each of the E and D series Resolvins, Protectins and Maresins was a critical and required step that enabled human clinical studies as in SPM profiling in COVID-19 infections and experimental animal disease models that also opened the promise of resolution physiology, resolution pharmacology and targeted precision nutrition as new areas for monitoring health and disease mechanisms.}, } @article {pmid35226158, year = {2022}, author = {Franquet, T and Giménez, A and Ketai, L and Mazzini, S and Rial, A and Pomar, V and Domingo, P}, title = {Air trapping in COVID-19 patients following hospital discharge: retrospective evaluation with paired inspiratory/expiratory thin-section CT.}, journal = {European radiology}, volume = {32}, number = {7}, pages = {4427-4436}, pmid = {35226158}, issn = {1432-1084}, support = {COV20/00070//instituto de salud carlos iii/ ; }, mesh = {*Bronchiectasis ; *COVID-19/complications ; Female ; Hospitals ; Humans ; Lung/diagnostic imaging ; Male ; Middle Aged ; Patient Discharge ; Retrospective Studies ; Tomography, X-Ray Computed/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: The study reports our experience with paired inspiration/expiration thin-section computed tomographic (CT) scans in the follow-up of COVID-19 patients with persistent respiratory symptoms.

METHODS: From August 13, 2020, to May 31, 2021, 48 long-COVID patients with respiratory symptoms (27 men and 21 women; median age, 62.0 years; interquartile range: 54.0-69.0 years) underwent follow-up paired inspiration-expiration thin-section CT scans. Patient demographics, length of hospital stay, intensive care unit admission rate, and clinical and laboratory features of acute infection were also included. The scans were obtained on a median of 72.5 days after onset of symptoms (interquartile range: 58.5-86.5) and at least 30 days after hospital discharge. Thin-section CT findings included ground-glass opacity, mosaic attenuation pattern, consolidation, traction bronchiectasis, reticulation, parenchymal bands, bronchial wall thickening, and air trapping. We used a quantitative score to determine the degree of air trapping in the expiratory scans.

RESULTS: Parenchymal abnormality was found in 50% (24/48) of patients and included air trapping (37/48, 77%), ground-glass opacities (19/48, 40%), reticulation (18/48, 38%), parenchymal bands (15/48, 31%), traction bronchiectasis (9/48, 19%), mosaic attenuation pattern (9/48, 19%), bronchial wall thickening (6/48, 13%), and consolidation (2/48, 4%). The absence of air trapping was observed in 11/48 (23%), mild air trapping in 20/48 (42%), moderate in 13/48 (27%), and severe in 4/48 (8%). Independent predictors of air trapping were, in decreasing order of importance, gender (p = 0.0085), and age (p = 0.0182).

CONCLUSIONS: Our results, in a limited number of patients, suggest that follow-up with paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping.

KEY POINTS: • Our experience indicates that paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. • Iterative reconstruction and dose-reduction options are recommended for demonstrating air trapping in long-COVID patients.}, } @article {pmid35223894, year = {2022}, author = {Maccio, U and Zinkernagel, AS and Schuepbach, R and Probst-Mueller, E and Frontzek, K and Brugger, SD and Hofmaenner, DA and Moch, H and Varga, Z}, title = {Long-Term Persisting SARS-CoV-2 RNA and Pathological Findings: Lessons Learnt From a Series of 35 COVID-19 Autopsies.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {778489}, pmid = {35223894}, issn = {2296-858X}, abstract = {BACKGROUND: Long-term sequelae of coronavirus disease 2019 (COVID-19), including the interaction between persisting viral-RNA and specific tissue involvement, pose a challenging issue. In this study, we addressed the chronological correlation (after first clinical diagnosis and postmortem) between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and organ involvement.

METHODS: The presence of postmortem SARS-CoV-2 RNA from 35 complete COVID-19 autopsies was correlated with the time interval between the first diagnosis of COVID-19 and death and with its relationship to morphologic findings.

RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be evident up to 40 days after the first diagnosis and can persist to 94 hours after death. Postmortem SARS-CoV-2 RNA was mostly positive in lungs (70%) and trachea (69%), but all investigated organs were positive with variable frequency. Late-stage tissue damage was evident up to 65 days after initial diagnosis in several organs. Positivity for SARS-CoV-2 RNA in pulmonary swabs correlated with diffuse alveolar damage (p = 0.0009). No correlation between positive swabs and other morphologic findings was present. Cerebral (p = 0.0003) and systemic hemorrhages (p = 0.009), cardiac thrombi (p = 0.04), and ischemic events (p = 0.03) were more frequent in the first wave, whereas bacterial pneumonia (p = 0.03) was more prevalent in the second wave. No differences in biometric data, clinical comorbidities, and other autopsy findings were found.

CONCLUSIONS: Our data provide evidence not only of long-term postmortem persisting SARS-CoV-2 RNA but also of tissue damage several weeks after the first diagnosis of SARS-CoV-2 infection. Additional conditions, such as concomitant bacterial pulmonary superinfection, lung aspergillosis, thromboembolic phenomena, and hemorrhages can further worsen tissue damage.}, } @article {pmid35223629, year = {2022}, author = {Yaksi, N and Teker, AG and Imre, A}, title = {Long COVID in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.}, journal = {Iranian journal of public health}, volume = {51}, number = {1}, pages = {88-95}, pmid = {35223629}, issn = {2251-6093}, abstract = {BACKGROUND: We aimed to evaluate the Long COVID frequency, and related factors in patients followed up after hospitalization.

METHODS: This retrospective cohort study included 133 inpatients with COVID-19 PCR test positivity from Nigde Province, Turkey between 01.01.2021 and 28.02.2021. The characteristics of the patients were recorded by examining the files, and the symptom questioning was made by telephone interviewing with the patients approximately four months after the date of diagnosis. The presence of at least one symptom lasting more than four weeks was described as Long COVID.

RESULTS: The frequency of Long COVID was 64.7%. The most common Long COVID symptoms were fatigue (45.9%), respiratory distress (25.6%), and muscle / joint pain (24.8%), respectively. In comparison analysis to identify factors associated with Long COVID; Long COVID was found to be more frequent among women (P=0.04); patients with severe COVID-19 (P<0.01), patients with prolonged hospital stay (P=0.03), patients with the comorbid disease (P=0.03), and Diabetes Mellitus patients (P=0.02). Additionally, the frequency of Long COVID increased as the depression score stated by the person increased after COVID-19 disease (P=0.02).

CONCLUSION: The treatment of COVID-19 patients should not end when they are discharged from the hospital. On the contrary, these patients, especially high-risk patients, should be followed up in post-COVID clinics and rehabilitated physically and psychosocially with a multidisciplinary approach following the recovery period of the acute illness.}, } @article {pmid35223315, year = {2022}, author = {Borkotokey, M}, title = {Scarred for Life as Covid-19 Leaves Its Mark: An Autobiographical Case Report.}, journal = {Cureus}, volume = {14}, number = {1}, pages = {e21542}, pmid = {35223315}, issn = {2168-8184}, abstract = {The COVID-19 pandemic affected humans in many more ways than one. The medical fraternity worked relentlessly, clad in personal protective equipment (PPE), to fight a virus that had taken the world by surprise. The irony is that, despite the PPE, our fraternity never felt so vulnerable and exposed. Yet, they stood out in handling the COVID-19 pandemic with due diligence. This case report describes the wearied experience of a healthcare worker affected by COVID-19 and its effect on physical and mental health. The author describes her experience as she suffered from COVID-19 and long COVID.}, } @article {pmid35221537, year = {2022}, author = {van Zitteren, M and van Boreen, MC and Spanjer, J}, title = {[Not Available].}, journal = {Tijdschrift voor bedrijfs- en verzekeringsgeneeskunde}, volume = {30}, number = {3}, pages = {36-40}, doi = {10.1007/s12498-022-1475-x}, pmid = {35221537}, issn = {1876-5858}, } @article {pmid35221210, year = {2022}, author = {Barthorpe, A and Rogers, JP}, title = {Coronavirus infections from 2002 to 2021: neuropsychiatric manifestations.}, journal = {Sleep medicine}, volume = {91}, number = {}, pages = {282-288}, pmid = {35221210}, issn = {1878-5506}, support = {102186/B/13/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications ; *Coronavirus 229E, Human ; *Delirium/epidemiology/etiology ; Humans ; *Severe acute respiratory syndrome-related coronavirus ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronaviruses have been known to infect humans for several decades and there are four endemic subtypes: HCoV (human coronavirus) -229E, -NL63, -OC43 and -HKU1. These mainly cause a mild upper respiratory illness, but occasionally in vulnerable individuals they can result in more severe respiratory disease and, rarely, CNS involvement. Prior exposure to these viruses has also been associated with an increased odds of having a major psychiatric illness. The severe acute respiratory syndrome (SARS), caused by SARS-CoV, started in 2002 and, as well as causing a more severe respiratory phenotype, was also associated with delirium and affective symptoms acutely. Psychosis occurred in about 1% of individuals and was generally thought to be due to corticosteroid administration. The Middle East respiratory syndrome (MERS), caused by MERS-CoV, revealed similar findings. Survivors of both SARS and MERS reported persistent physical and psychological symptoms at least several months after the acute illness. The reported neuropsychiatric symptoms of COVID-19 range from the common symptoms of systemic and upper respiratory infections to severe and disabling conditions. Delirium has been described using varying terminology; as well as being a possible presenting feature of COVID-19, it has also been shown to be a marker of severe disease. Stroke, both ischaemic and haemorrhagic, have been reported to be more common in COVID-19 than in other medical illnesses. Mood and anxiety disorders are likely to be common at follow-up, while psychosis remains rare and controversial. 'Long Covid' is likely to represent a highly clinically and aetiologically heterogeneous group.}, } @article {pmid35219440, year = {2022}, author = {Butler, M and Cross, B and Hafeez, D and Lim, MF and Morrin, H and Rengasamy, ER and Pollak, T and Nicholson, TR}, title = {Emerging Knowledge of the Neurobiology of COVID-19.}, journal = {The Psychiatric clinics of North America}, volume = {45}, number = {1}, pages = {29-43}, pmid = {35219440}, issn = {1558-3147}, mesh = {*COVID-19/complications ; Humans ; Nervous System Diseases/*virology ; Neurobiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.}, } @article {pmid35219086, year = {2022}, author = {Chidambaram, V and Kumar, A and Calcaterra, G and Mehta, JL}, title = {Persistent cardiac injury - An important component of long COVID-19 syndrome.}, journal = {EBioMedicine}, volume = {77}, number = {}, pages = {103892}, pmid = {35219086}, issn = {2352-3964}, mesh = {*COVID-19/complications ; *Heart Diseases ; *Heart Injuries ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35216882, year = {2022}, author = {Chuang, HJ and Hsiao, MY and Wang, TG and Liang, HW}, title = {A multi-disciplinary rehabilitation approach for people surviving severe COVID-19-a case series and literature review.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {121}, number = {12}, pages = {2408-2415}, pmid = {35216882}, issn = {0929-6646}, mesh = {Humans ; *COVID-19 ; Critical Illness ; Activities of Daily Living ; Taiwan ; }, abstract = {BACKGROUND/PURPOSE: COronaVIrus Disease 2019 (COVID-19) has caused tremendous casualties and morbidities worldwide. Multisystem manifestations, including muscle weakness, dyspnea, cognitive decline, dysphagia, and dysarthria are frequently reported among critically ill patients. The resultant activity limitations and participation restrictions call for an organized and multidisciplinary approach to rehabilitation. Taiwan had a rapid surge in community infection cases from May to July 2021, and our team established a team-based approach in response to the rehabilitation needs for the in-patients, especially the critically-ill group.

METHODS: We built a core treatment team and established a referral pathway for critically ill patients with COVID-19 based on a multidisciplinary approach. The care process and outcomes of a case series of patients who received in-patient rehabilitation after medical stabilization were presented.

RESULTS: Our clinical care module was established according to interim World Health Organization guidance and current research and demonstrated a high degree of feasibility. Five patients with multiple impairments received in-patient rehabilitation and experienced significant functional improvement. We documented improvements in motor function, swallowing function, and activities of daily living after the rehabilitation.

CONCLUSION: Our clinical experience suggests considerable benefits can be obtained from a well-organized and multidisciplinary rehabilitation approach for severe COVID-19 patients.}, } @article {pmid35216672, year = {2022}, author = {Su, Y and Yuan, D and Chen, DG and Ng, RH and Wang, K and Choi, J and Li, S and Hong, S and Zhang, R and Xie, J and Kornilov, SA and Scherler, K and Pavlovitch-Bedzyk, AJ and Dong, S and Lausted, C and Lee, I and Fallen, S and Dai, CL and Baloni, P and Smith, B and Duvvuri, VR and Anderson, KG and Li, J and Yang, F and Duncombe, CJ and McCulloch, DJ and Rostomily, C and Troisch, P and Zhou, J and Mackay, S and DeGottardi, Q and May, DH and Taniguchi, R and Gittelman, RM and Klinger, M and Snyder, TM and Roper, R and Wojciechowska, G and Murray, K and Edmark, R and Evans, S and Jones, L and Zhou, Y and Rowen, L and Liu, R and Chour, W and Algren, HA and Berrington, WR and Wallick, JA and Cochran, RA and Micikas, ME and , and Wrin, T and Petropoulos, CJ and Cole, HR and Fischer, TD and Wei, W and Hoon, DSB and Price, ND and Subramanian, N and Hill, JA and Hadlock, J and Magis, AT and Ribas, A and Lanier, LL and Boyd, SD and Bluestone, JA and Chu, H and Hood, L and Gottardo, R and Greenberg, PD and Davis, MM and Goldman, JD and Heath, JR}, title = {Multiple early factors anticipate post-acute COVID-19 sequelae.}, journal = {Cell}, volume = {185}, number = {5}, pages = {881-895.e20}, pmid = {35216672}, issn = {1097-4172}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; T32 AI007334/AI/NIAID NIH HHS/United States ; R21 AI138258/AI/NIAID NIH HHS/United States ; R01 DA040395/DA/NIDA NIH HHS/United States ; UG3 TR002884/TR/NCATS NIH HHS/United States ; R01 AI068129/AI/NIAID NIH HHS/United States ; P01 AI153559/AI/NIAID NIH HHS/United States ; R01 AI155685/AI/NIAID NIH HHS/United States ; T32 AI007044/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; U19 AI128914/AI/NIAID NIH HHS/United States ; R01 AI163131/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity/genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies/blood ; Biomarkers/metabolism ; Blood Proteins/metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism ; COVID-19/*complications/*diagnosis/immunology/pathology/virology ; *Convalescence ; Disease Progression ; Female ; Humans ; Immunity, Innate/genetics ; Longitudinal Studies ; Male ; Middle Aged ; Risk Factors ; SARS-CoV-2/isolation & purification ; Transcriptome ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8[+] T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.}, } @article {pmid35216286, year = {2022}, author = {Russo, A and Tellone, E and Barreca, D and Ficarra, S and Laganà, G}, title = {Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216286}, issn = {1422-0067}, mesh = {Anemia/virology ; Antiviral Agents/pharmacology ; COVID-19/*blood/complications/*diet therapy/etiology/metabolism ; Erythrocytes/metabolism/pathology/*virology ; Hemoglobins/metabolism ; Hemolysis ; Humans ; Oxidative Stress ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells. Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.}, } @article {pmid35215365, year = {2022}, author = {Albanese, M and Marrone, G and Paolino, A and Di Lauro, M and Di Daniele, F and Chiaramonte, C and D'Agostini, C and Romani, A and Cavaliere, A and Guerriero, C and Magrini, A and Mercuri, NB and Di Daniele, N and Noce, A}, title = {Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case-Control Study.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, pmid = {35215365}, issn = {1424-8247}, abstract = {Ultramicronized palmitoylethanolamide (um-PEA), a compound with antioxidant, anti-inflammatory and neuroprotective properties, appears to be a potential adjuvant treatment for early stages of Coronavirus disease 2019 (COVID-19). In our study, we enrolled 90 patients with confirmed diagnosis of COVID-19 that were randomized into two groups, homogeneous for age, gender and BMI. The first group received oral supplementation based on um-PEA at a dose of 1800 mg/day for a total of 28 days; the second group was the control group (R.S. 73.20). At baseline (T0) and after 28 days of um-PEA treatment (T1), we monitored: routine laboratory parameters, inflammatory and oxidative stress (OS) biomarkers, lymphocytes subpopulation and COVID-19 serological response. At T1, the um-PEA-treated group presented a significant reduction in inflammation compared to the control group (CRP p = 0.007; IL-6 p = 0.0001; neutrophils to lymphocytes ratio p = 0.044). At T1, the controls showed a significant increase in OS compared to the treated group (FORT p = 0.05). At T1, the um-PEA group exhibited a significant decrease in D-dimer levels (p = 0.0001) and higher levels of IgG against SARS-CoV-2 (p = 0.0001) compared to the controls. Our data demonstrated, in a randomized clinical trial, the beneficial effects of um-PEA in both asymptomatic and mild-symptomatic patients related to reductions in inflammatory state, OS and coagulative cascade alterations.}, } @article {pmid35215212, year = {2022}, author = {Han, Q and Zheng, B and Daines, L and Sheikh, A}, title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {2}, pages = {}, pmid = {35215212}, issn = {2076-0817}, support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18-39), dyspnoea (18%, 95% CI: 13-24), arthromyalgia (26%, 95% CI: 8-44), depression (23%, 95% CI: 12-34), anxiety (22%, 95% CI: 15-29), memory loss (19%, 95% CI: 7-31), concentration difficulties (18%, 95% CI: 2-35), and insomnia (12%, 95% CI: 7-17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients.}, } @article {pmid35214624, year = {2022}, author = {Varnai, R and Molnar, T and Zavori, L and Tőkés-Füzesi, M and Illes, Z and Kanizsai, A and Csecsei, P}, title = {Serum Level of Anti-Nucleocapsid, but Not Anti-Spike Antibody, Is Associated with Improvement of Long COVID Symptoms.}, journal = {Vaccines}, volume = {10}, number = {2}, pages = {}, pmid = {35214624}, issn = {2076-393X}, abstract = {BACKGROUND: Long COVID is a condition characterized by long-term sequelae persisting after the typical convalescence period of COVID-19. Previous reports have suggested the role of an unsatisfactory immune response and impaired viral clearance in the pathogenesis of long COVID syndrome. We focused on potential associations between post-vaccination changes of antibody titers and the severity of long COVID symptoms and factors influencing the state of remission observed in patients with long COVID after vaccination.

METHODS: The severity of long COVID symptoms and serum anti-SARS-CoV-2 spike (S-Ig) and nucleocapsid (NC-Ig) levels were assessed in 107 post-COVID subjects at two time points: at baseline, and 17-24 weeks later. Besides, vaccination status was also assessed. Symptoms were evaluated based on the Chalder fatigue scale (CFQ-11) and visual analogue scale (VAS).

RESULTS: Serum level of S-Ig and NC-Ig at baseline were significantly higher in the patients with non-severe fatigue than those with severe fatigue, and this difference remained significant at follow-up in the case of NC-Ig. NC-Ig level above median was as an independent predictor for complete remission at follow-up. The difference in NC-Ig levels in subgroup analyses (severe fatigue vs. non-severe fatigue; complete remission vs. incomplete remission or progression) was found to be significant only in patients who received vaccination.

CONCLUSIONS: The immune response against the SARS-CoV-2 nucleocapsid may play a more important role than the spike in the course of long-term COVID syndrome.}, } @article {pmid35214599, year = {2022}, author = {Shiri, T and Evans, M and Talarico, CA and Morgan, AR and Mussad, M and Buck, PO and McEwan, P and Strain, WD}, title = {The Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program.}, journal = {Vaccines}, volume = {10}, number = {2}, pages = {}, pmid = {35214599}, issn = {2076-393X}, support = {NA//Moderna Therapeutics (United States)/ ; }, abstract = {The vaccination program is reducing the burden of COVID-19. However, recently, COVID-19 infections have been increasing across Europe, providing evidence that vaccine efficacy is waning. Consequently, booster doses are required to restore immunity levels. However, the relative risk-benefit ratio of boosters, compared to pursuing a primary course in the unvaccinated population, remains uncertain. In this study, a susceptible-exposed-infectious-recovered (SEIR) transmission model of SARS-CoV-2 was used to investigate the impact of COVID-19 vaccine waning on disease burden, the benefit of a booster vaccine program compared to targeting the unvaccinated population, and the population-wide risk-benefit profile of vaccination. Our data demonstrates that the rate of vaccine efficacy waning has a significant impact on COVID-19 hospitalisations with the greatest effect in populations with lower vaccination coverage. There was greater benefit associated with a booster vaccination strategy compared to targeting the unvaccinated population, once >50% of the population had received their primary vaccination course. The population benefits of vaccination (reduced hospitalisations, long-COVID and deaths) outweighed the risks of myocarditis/pericarditis by an order of magnitude. Vaccination is important in ending the COVID-19 pandemic sooner, and the reduction in hospitalisations, death and long-COVID associated with vaccination significantly outweigh any risks. Despite these obvious benefits some people are vaccine reluctant, and as such remain unvaccinated. However, when most of a population have been vaccinated, a focus on a booster vaccine strategy for this group is likely to offer greater value, than targeting the proportion of the population who choose to remain unvaccinated.}, } @article {pmid35213866, year = {2022}, author = {Zimmermann, P and Pittet, LF and Curtis, N}, title = {The Challenge of Studying Long COVID: An Updated Review.}, journal = {The Pediatric infectious disease journal}, volume = {41}, number = {5}, pages = {424-426}, pmid = {35213866}, issn = {1532-0987}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Pandemics ; Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Accurately determining the risk of long COVID is challenging. Existing studies in children and adolescents have considerable limitations and distinguishing long-term SARS-CoV-2 infection-associated symptoms from pandemic-related symptoms is difficult. Over half of individuals in this age group, irrespective of COVID-19, report physical and psychologic symptoms, highlighting the impact of the pandemic. More robust data is needed to inform policy decisions.}, } @article {pmid35212063, year = {2022}, author = {Vestad, B and Ueland, T and Lerum, TV and Dahl, TB and Holm, K and Barratt-Due, A and Kåsine, T and Dyrhol-Riise, AM and Stiksrud, B and Tonby, K and Hoel, H and Olsen, IC and Henriksen, KN and Tveita, A and Manotheepan, R and Haugli, M and Eiken, R and Berg, Å and Halvorsen, B and Lekva, T and Ranheim, T and Michelsen, AE and Kildal, AB and Johannessen, A and Thoresen, L and Skudal, H and Kittang, BR and Olsen, RB and Ystrøm, CM and Skei, NV and Hannula, R and Aballi, S and Kvåle, R and Skjønsberg, OH and Aukrust, P and Hov, JR and Trøseid, M and , }, title = {Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.}, journal = {Journal of internal medicine}, volume = {291}, number = {6}, pages = {801-812}, pmid = {35212063}, issn = {1365-2796}, mesh = {*COVID-19/complications ; Clinical Trials as Topic ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown.

METHODS: Plasma was collected during hospital admission and after 3 months from the NOR-Solidarity trial (n = 181) and analyzed for markers of gut barrier dysfunction and inflammation. At the 3-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO). Rectal swabs for gut microbiota analyses were collected (n = 97) and analyzed by sequencing the 16S rRNA gene.

RESULTS: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal 3 months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP levels remained elevated during and after hospitalization and were associated with low-grade inflammation and respiratory dysfunction after 3 months.

CONCLUSION: Respiratory dysfunction after COVID-19 is associated with altered gut microbiota and persistently elevated LBP levels. Our results should be regarded as hypothesis generating, pointing to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID.}, } @article {pmid35211871, year = {2022}, author = {Caspersen, IH and Magnus, P and Trogstad, L}, title = {Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort.}, journal = {European journal of epidemiology}, volume = {37}, number = {5}, pages = {539-548}, pmid = {35211871}, issn = {1573-7284}, support = {262700//Norges Forskningsråd/ ; }, mesh = {Adult ; *COVID-19/complications/epidemiology ; Child ; Cohort Studies ; Fatigue/epidemiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Physical, psychological and cognitive symptoms have been reported as post-acute sequelae for COVID-19 patients but are also common in the general uninfected population. We aimed to calculate the excess risk and identify patterns of 22 symptoms up to 12 months after COVID-19. We followed more than 70,000 adult participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. Infected and non-infected participants registered presence of 22 different symptoms in March 2021. One year after infection, 13 of 22 symptoms were associated with SARS-CoV-2 infection, based on relative risks between infected and uninfected subjects. For instance, 17.4% of SARS-CoV-2 infected cohort participants reported fatigue that persist 12 months after infection, compared to new occurrence of fatigue that had lasted less than 12 months in 3.8% of non-infected subjects (excess risk 13.6%). The adjusted relative risk for fatigue was 4.8 (95% CI 3.5-6.7). Two main underlying factors explained 50% of the variance in the 13 symptoms. Brain fog, poor memory, dizziness, heart palpitations, and fatigue had high loadings on the first factor, while shortness-of breath and cough had high loadings on the second factor. Lack of taste and smell showed low to moderate correlation to other symptoms. Anxiety, depression and mood swings were not strongly related to COVID-19. Our results suggest that there are clusters of symptoms after COVID-19 due to different mechanisms and question whether it is meaningful to describe long COVID as one syndrome.}, } @article {pmid35207572, year = {2022}, author = {Fainardi, V and Meoli, A and Chiopris, G and Motta, M and Skenderaj, K and Grandinetti, R and Bergomi, A and Antodaro, F and Zona, S and Esposito, S}, title = {Long COVID in Children and Adolescents.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207572}, issn = {2075-1729}, abstract = {Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.}, } @article {pmid35207429, year = {2022}, author = {Vaira, LA and Gessa, C and Deiana, G and Salzano, G and Maglitto, F and Lechien, JR and Saussez, S and Piombino, P and Biglio, A and Biglioli, F and Boscolo-Rizzo, P and Hopkins, C and Parma, V and De Riu, G}, title = {The Effects of Persistent Olfactory and Gustatory Dysfunctions on Quality of Life in Long-COVID-19 Patients.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35207429}, issn = {2075-1729}, abstract = {(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.}, } @article {pmid35207171, year = {2022}, author = {Yelin, D and Margalit, I and Nehme, M and Bordas-Martínez, J and Pistelli, F and Yahav, D and Guessous, I and Durà-Miralles, X and Carrozzi, L and Shapira-Lichter, I and Vetter, P and Peleato-Catalan, D and Tiseo, G and Wirtheim, E and Kaiser, L and Gudiol, C and Falcone, M and Leibovici, L and On Behalf Of The LongCOV Research Group, }, title = {Patterns of Long COVID Symptoms: A Multi-Center Cross Sectional Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {4}, pages = {}, pmid = {35207171}, issn = {2077-0383}, support = {2021//Israeli Insurance Association research fund/ ; }, abstract = {BACKGROUND: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients.

METHODS: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients' characteristics, features of acute disease and effect on daily life were sought.

RESULTS: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5-9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status.

CONCLUSION: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions.}, } @article {pmid35207003, year = {2022}, author = {Vink, M and Vink-Niese, F}, title = {Is It Useful to Question the Recovery Behaviour of Patients with ME/CFS or Long COVID?.}, journal = {Healthcare (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {35207003}, issn = {2227-9032}, abstract = {For the last few decades, medical guidelines have recommended treating patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with graded exercise therapy (GET) and cognitive behavioural therapy (CBT). Moreover, doctors have questioned the recovery behaviour of these patients and stimulated them to follow these treatments so that they would be able to go back to work. In this article, we reviewed trials of GET and CBT for ME/CFS that reported on work status before and after treatment to answer the question of whether doctors should continue to question the recovery behaviour of patients with ME/CFS. Our review shows that more patients are unable to work after treatment than before treatment with CBT and GET. It also highlights the fact that both treatments are unsafe for patients with ME/CFS. Therefore, questioning the recovery behaviour of patients with ME/CFS is pointless. This confirms the conclusion from the British National Institute for Health and Care Excellence (NICE), which has recently published its updated ME/CFS guideline and concluded that CBT and GET are not effective and do not lead to recovery. Studies on CBT and GET for long COVID have not yet been published. However, this review offers no support for their use in improving the recovery of patients with an ME/CFS-like illness after infection with COVID-19, nor does it lend any support to the practice of questioning the recovery behaviour of these patients.}, } @article {pmid35206616, year = {2022}, author = {Platten, M and Nienhaus, A and Peters, C and Cranen, R and Wisplinghoff, H and Kersten, JF and Bach, AD and Michels, G}, title = {Cumulative Incidence of SARS-CoV-2 in Healthcare Workers at a General Hospital in Germany during the Pandemic-A Longitudinal Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {4}, pages = {}, pmid = {35206616}, issn = {1660-4601}, support = {ext. FF_1461//Department for Occupational Medicine, Hazardous Substances and Health Sciences (AGG), Institution for Statutory Accident Insurance in the Health and Welfare Services (BGW), Hamburg 22089, Germany/ ; }, mesh = {*COVID-19/complications/epidemiology ; Germany/epidemiology ; Health Personnel ; Hospitals, General ; Humans ; Incidence ; Pandemics/prevention & control ; Quality of Life ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Health workers (HW) are at increased risk for SARS-CoV-2 infection. In order to monitor the infection dynamic on the basis of contact with patients, HW at the St. Antonius Hospital (SAH) were tested four times in one year by PCR and serology. The cumulative incidence of infection in HW was calculated. Swab and blood tests were simultaneously performed between April 2020 and April 2021. Risk factors and demographic information were assessed at the beginning of the study. The response rate was above 75% in all rounds of testing. The study comprised 1506 HW, 165 (10.6%) of which tested positive for SARS-CoV-2 infection. Working in an ICU or on wards with patient contact were risk factors (OR 4.4, 95% CI 1.73-13.6 and OR 2.9, 95% CI 1.27-8.49). At the end of the study, the majority of HW (810 of 1363 (59.4%)) had been vaccinated at least once. A total of 29.1% of unvaccinated HW and 5.3% of vaccinated HW showed an immune response typical for natural SARS-CoV-2 infection. Of the 73 HW who provided information on the course of the disease, 31.5% reported that their quality of life continued to be impaired. The cumulative incidence of infection was low in these HW, which may be attributed to vaccination and good hygiene. Nevertheless, a work-related infection risk was identified, highlighting the need to improve protection against infection. A high risk of developing long COVID was found after the infection has subsided. Special rehabilitation programs should be provided and HW should be compensated for reduced work capacity in the case that rehabilitation fails or takes a long time.}, } @article {pmid35205026, year = {2022}, author = {Bellanti, F and Lo Buglio, A and Vendemiale, G}, title = {Redox Homeostasis and Immune Alterations in Coronavirus Disease-19.}, journal = {Biology}, volume = {11}, number = {2}, pages = {}, pmid = {35205026}, issn = {2079-7737}, abstract = {The global Coronavirus Disease 2019 (COVID-19) pandemic is characterized by a wide variety of clinical features, from no or moderate symptoms to severe illness. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that first affects the respiratory tract. Other than being limited to lungs, SARS-CoV-2 may lead to a multisystem disease that can even be durable (long COVID). The clinical spectrum of COVID-19 depends on variability in the immune regulation. Indeed, disease progression is consequent to failure in the immune regulation, characterized by an intensification of the pro-inflammatory response. Disturbance of systemic and organ-related redox balance may be a further mechanism underlying variability in COVID-19 severity. Other than being determinant for SARS-CoV-2 entry and fusion to the host cell, reactive species and redox signaling are deeply involved in the immune response. This review sums up the present knowledge on the role of redox balance in the regulation of susceptibility to SARS-CoV-2 infection and related immune response, debating the effectiveness of antioxidant compounds in the management of COVID-19.}, } @article {pmid35204999, year = {2022}, author = {Buonsenso, D and Mariani, F and Pierri, L and Morello, R and Yock-Corrales, A and Del Aguila, O and Lazzareschi, I and Zampino, G and Nunziata, F and Valentini, P and Lo Vecchio, A}, title = {Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {2}, pages = {}, pmid = {35204999}, issn = {2227-9067}, abstract = {Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62-10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19.}, } @article {pmid35203918, year = {2022}, author = {Di Stadio, A and Brenner, MJ and De Luca, P and Albanese, M and D'Ascanio, L and Ralli, M and Roccamatisi, D and Cingolani, C and Vitelli, F and Camaioni, A and Di Girolamo, S and Bernitsas, E}, title = {Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study.}, journal = {Brain sciences}, volume = {12}, number = {2}, pages = {}, pmid = {35203918}, issn = {2076-3425}, abstract = {Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.}, } @article {pmid35203555, year = {2022}, author = {Chutipongtanate, S and Morrow, AL and Newburg, DS}, title = {Human Milk Oligosaccharides: Potential Applications in COVID-19.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, pmid = {35203555}, issn = {2227-9059}, abstract = {Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global health crisis with more than four million deaths worldwide. A substantial number of COVID-19 survivors continue suffering from long-COVID syndrome, a long-term complication exhibiting chronic inflammation and gut dysbiosis. Much effort is being expended to improve therapeutic outcomes. Human milk oligosaccharides (hMOS) are non-digestible carbohydrates known to exert health benefits in breastfed infants by preventing infection, maintaining immune homeostasis and nurturing healthy gut microbiota. These beneficial effects suggest the hypothesis that hMOS might have applications in COVID-19 as receptor decoys, immunomodulators, mucosal signaling agents, and prebiotics. This review summarizes hMOS biogenesis and classification, describes the possible mechanisms of action of hMOS upon different phases of SARS-CoV-2 infection, and discusses the challenges and opportunities of hMOS research for clinical applications in COVID-19.}, } @article {pmid35203084, year = {2022}, author = {Nopp, S and Moik, F and Klok, FA and Gattinger, D and Petrovic, M and Vonbank, K and Koczulla, AR and Ay, C and Zwick, RH}, title = {Outpatient Pulmonary Rehabilitation in Patients with Long COVID Improves Exercise Capacity, Functional Status, Dyspnea, Fatigue, and Quality of Life.}, journal = {Respiration; international review of thoracic diseases}, volume = {101}, number = {6}, pages = {593-601}, pmid = {35203084}, issn = {1423-0356}, mesh = {*COVID-19/complications ; Dyspnea ; Exercise Tolerance/physiology ; Fatigue/etiology ; Female ; Functional Status ; Humans ; Male ; Middle Aged ; Outpatients ; Prospective Studies ; *Pulmonary Disease, Chronic Obstructive ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: COVID-19 survivors face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations. Pulmonary rehabilitation has been recommended, although formal studies quantifying the effect of rehabilitation in COVID-19 patients are lacking.

METHODS: We conducted a prospective observational cohort study including consecutive patients admitted to an outpatient pulmonary rehabilitation center due to persistent symptoms after COVID-19. The primary endpoint was change in 6-min walk distance (6MWD) after undergoing a 6-week interdisciplinary individualized pulmonary rehabilitation program. Secondary endpoints included change in the post-COVID-19 functional status (PCFS) scale, Borg dyspnea scale, Fatigue Assessment Scale, and quality of life. Further, changes in pulmonary function tests were explored.

RESULTS: Of 64 patients undergoing rehabilitation, 58 patients (mean age 47 years, 43% women, 38% severe/critical COVID-19) were included in the per-protocol-analysis. At baseline (i.e., in mean 4.4 months after infection onset), mean 6MWD was 584.1 m (±95.0), and functional impairment was graded in median at 2 (IQR, 2-3) on the PCFS. On average, patients improved their 6MWD by 62.9 m (±48.2, p < 0.001) and reported an improvement of 1 grade on the PCFS scale. Accordingly, we observed significant improvements across secondary endpoints including presence of dyspnea (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Also, pulmonary function parameters (forced expiratory volume in 1 s, lung diffusion capacity, inspiratory muscle pressure) significantly increased during rehabilitation.

CONCLUSION: In patients with long COVID, exercise capacity, functional status, dyspnea, fatigue, and quality of life improved after 6 weeks of personalized interdisciplinary pulmonary rehabilitation. Future studies are needed to establish the optimal protocol, duration, and long-term benefits as well as cost-effectiveness of rehabilitation.}, } @article {pmid35200155, year = {2022}, author = {Houben-Wilke, S and Goërtz, YM and Delbressine, JM and Vaes, AW and Meys, R and Machado, FV and van Herck, M and Burtin, C and Posthuma, R and Franssen, FM and Vijlbrief, H and Spies, Y and van 't Hul, AJ and Spruit, MA and Janssen, DJ}, title = {The Impact of Long COVID-19 on Mental Health: Observational 6-Month Follow-Up Study.}, journal = {JMIR mental health}, volume = {9}, number = {2}, pages = {e33704}, pmid = {35200155}, issn = {2368-7959}, abstract = {BACKGROUND: The psychological impact of COVID-19 can be substantial. However, knowledge about long-term psychological outcomes in patients with COVID-19 is scarce.

OBJECTIVE: In this longitudinal, observational study, we aimed to reveal symptoms of posttraumatic stress disorder (PTSD) and symptoms of anxiety and depression up to 6 months after the onset of COVID-19-related symptoms in patients with confirmed COVID-19 and persistent complaints. To demonstrate the impact in nonhospitalized patients, we further aimed to compare these outcomes between nonhospitalized and hospitalized patients.

METHODS: Demographics, symptoms of PTSD (Trauma Screening Questionnaire [TSQ] ≥6 points) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS] ≥8 points) were assessed at 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID-19 peer support groups.

RESULTS: Data from 239 patients with confirmed COVID-19 (198/239, 82.8% female; median age: 50 [IQR 39-56] years) were analyzed. At the 3-month follow-up, 37.2% (89/239) of the patients had symptoms of PTSD, 35.6% (85/239) had symptoms of anxiety, and 46.9% (112/239) had symptoms of depression, which remained high at the 6-month follow-up (64/239, 26.8%, P=.001; 83/239, 34.7%, P=.90; 97/239, 40.6%, P=.08, respectively; versus the 3-month follow-up). TSQ scores and HADS anxiety and depression scores were strongly correlated at the 3- and 6-month follow-ups (r=0.63-0.71, P<.001). Symptoms of PTSD, anxiety, and depression were comparable between hospitalized (n=62) and nonhospitalized (n=177) patients.

CONCLUSIONS: A substantial percentage of patients with confirmed COVID-19 and persistent complaints reported symptoms of PTSD, anxiety, or depression 3 and 6 months after the onset of COVID-19-related symptoms. The prevalence rates of symptoms of PTSD, anxiety, and depression were comparable between hospitalized and nonhospitalized patients and merely improved over time. Health care professionals need to be aware of these psychological complications and intervene on time in post-COVID-19 patients with persistent complaints.

TRIAL REGISTRATION: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.}, } @article {pmid35198158, year = {2022}, author = {Selvaskandan, H and Nimmo, A and Savino, M and Afuwape, S and Brand, S and Graham-Brown, M and Medcalf, J and Cockwell, P and Beckwith, H}, title = {Burnout and long COVID among the UK nephrology workforce: results from a national survey investigating the impact of COVID-19 on working lives.}, journal = {Clinical kidney journal}, volume = {15}, number = {3}, pages = {517-526}, pmid = {35198158}, issn = {2048-8505}, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is placing a significant strain on healthcare. We conducted a national survey of the UK nephrology workforce to understand its impacts on their working lives.

METHODS: An online questionnaire incorporating the Maslach Burnout Inventory score was distributed between 31 March and 1 May 2021, with a focus on COVID-19 and long COVID incidence, vaccine uptake, burnout and working patterns. Data were analysed qualitatively and quantitatively; multivariable logistic regression was used to identify associations.

RESULTS: A total of 423 responses were received. Of them, 29% had contracted COVID-19, which was more common among doctors and nurses {odds ratio [OR] 2.18 [95% confidence interval (CI) 1.13-4.22]} and those <55 years of age [OR 2.60 (95% CI 1.38-4.90)]. Of those who contracted COVID-19, 36% had symptoms of long COVID, which was more common among ethnicities other than White British [OR 2.57 (95% CI 1.09-6.05)]. A total of 57% had evidence of burnout, which was more common among younger respondents [OR 1.92 (95% CI 1.10-3.35)] and those with long COVID [OR 10.31 (95% CI 1.32-80.70)], and 59% with reconfigured job plans continued to work more hours. More of those working full-time wished to retire early. A total of 59% experienced remote working, with a majority preference for continuing this in the future. In terms of vaccination, 95% had received one dose of a COVID-19 vaccine and 86% had received two doses by May 2021.

CONCLUSIONS: Burnout and long COVID is prevalent with impacts on working lives. Some groups are more at risk. Vaccination uptake is high and remote and flexible working were well received. Institutional interventions are needed to prevent workforce attrition.}, } @article {pmid35198136, year = {2022}, author = {Stefanou, MI and Palaiodimou, L and Bakola, E and Smyrnis, N and Papadopoulou, M and Paraskevas, GP and Rizos, E and Boutati, E and Grigoriadis, N and Krogias, C and Giannopoulos, S and Tsiodras, S and Gaga, M and Tsivgoulis, G}, title = {Neurological manifestations of long-COVID syndrome: a narrative review.}, journal = {Therapeutic advances in chronic disease}, volume = {13}, number = {}, pages = {20406223221076890}, pmid = {35198136}, issn = {2040-6223}, abstract = {Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for 'long-COVID' diagnosis. Nevertheless, 'long-COVID' is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of 'long-COVID' encompass fatigue; 'brain fog'; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of 'long-COVID', neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological 'long-COVID' sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological 'long-COVID' sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for 'long-COVID' are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological 'long-COVID' symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological 'long-COVID' sequelae.}, } @article {pmid35195253, year = {2022}, author = {Kell, DB and Laubscher, GJ and Pretorius, E}, title = {A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications.}, journal = {The Biochemical journal}, volume = {479}, number = {4}, pages = {537-559}, pmid = {35195253}, issn = {1470-8728}, mesh = {*Amyloid/blood/chemistry ; Anticoagulants/*therapeutic use ; *COVID-19/blood ; Fibrin/chemistry/metabolism ; Humans ; *Lung/metabolism/virology ; SARS-CoV-2/*metabolism ; *Thrombosis/drug therapy/metabolism/virology ; *COVID-19 Drug Treatment ; }, abstract = {Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.}, } @article {pmid35194745, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Navarro-Pardo, E and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Pellicer-Valero, OJ}, title = {Exploring Trajectory Curves from Loss of Smell and Taste in Previously Hospitalized COVID-19 Survivors: the LONG-COVID-EXP-CM Multicenter Study.}, journal = {Journal of general internal medicine}, volume = {37}, number = {7}, pages = {1821-1823}, pmid = {35194745}, issn = {1525-1497}, mesh = {Anosmia ; *COVID-19/complications ; Humans ; Survivors ; Taste ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35193574, year = {2022}, author = {Rivera-Izquierdo, M and Láinez-Ramos-Bossini, AJ and de Alba, IG and Ortiz-González-Serna, R and Serrano-Ortiz, Á and Fernández-Martínez, NF and Ruiz-Montero, R and Cervilla, JA}, title = {Long COVID 12 months after discharge: persistent symptoms in patients hospitalised due to COVID-19 and patients hospitalised due to other causes-a multicentre cohort study.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {92}, pmid = {35193574}, issn = {1741-7015}, mesh = {Adult ; *COVID-19/complications ; Cohort Studies ; Hospitalization ; Humans ; Patient Discharge ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-term-specific sequelae or persistent symptoms (SPS) after hospitalisation due to COVID-19 are not known. The aim of this study was to explore the presence of SPS 12 months after discharge in survivors hospitalised due to COVID-19 and compare it with survivors hospitalised due to other causes.

METHODS: Prospective cohort study, the Andalusian Cohort of Hospitalised patients for COVID-19 (ANCOHVID study), conducted in 4 hospitals and 29 primary care centres in Andalusia, Spain. The sample was composed of 906 adult patients; 453 patients hospitalised due to COVID-19 (exposed) and 453 hospitalised due to other causes (non-exposed) from March 1 to April 15, 2020, and discharged alive. The main outcomes were (1) the prevalence of SPS at 12 months after discharge and (2) the incidence of SPS after discharge. Outcome data at 12 months were compared between the exposed and non-exposed cohorts. Risk ratios were calculated, and bivariate analyses were performed.

RESULTS: A total of 163 (36.1%) and 160 (35.3%) patients of the exposed and non-exposed cohorts, respectively, showed at least one SPS at 12 months after discharge. The SPS with higher prevalence in the subgroup of patients hospitalised due to COVID-19 12 months after discharge were persistent pharyngeal symptoms (p<0.001), neurological SPS (p=0.049), confusion or memory loss (p=0.043), thrombotic events (p=0.025) and anxiety (p=0.046). The incidence of SPS was higher for the exposed cohort regarding pharyngeal symptoms (risk ratio, 8.00; 95% CI, 1.85 to 36.12), confusion or memory loss (risk ratio, 3.50; 95% CI, 1.16 to 10.55) and anxiety symptoms (risk ratio, 2.36; 95% CI, 1.28 to 4.34).

CONCLUSIONS: There was a similar frequency of long-term SPS after discharge at 12 months, regardless of the cause of admission (COVID-19 or other causes). Nevertheless, some symptoms that were found to be more associated with COVID-19, such as memory loss or anxiety, merit further investigation. These results should guide future follow-up of COVID-19 patients after hospital discharge.}, } @article {pmid35191397, year = {2022}, author = {Tian, T and Wu, J and Chen, T and Li, J and Yan, S and Zhou, Y and Peng, X and Li, Y and Zheng, N and Cai, A and Ning, Q and Xiang, H and Xu, F and Qin, Y and Zhu, W and Wang, J}, title = {Long-term follow-up of dynamic brain changes in patients recovered from COVID-19 without neurological manifestations.}, journal = {JCI insight}, volume = {7}, number = {4}, pages = {}, pmid = {35191397}, issn = {2379-3708}, mesh = {Brain/*pathology ; COVID-19/complications/*pathology/virology ; Female ; Humans ; Male ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUNDAfter the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as "long COVID" - even those without specific neurological manifestations in the acute phase.METHODSDynamic brain changes are crucial for a better understanding and early prevention of "long COVID." Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge.RESULTSOverall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases.CONCLUSIONOur study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of "long COVID" and early clinical guidance toward complete recovery.FUNDINGNational Natural Science Foundation of China.}, } @article {pmid35188188, year = {2022}, author = {Kambic, T and Hadžić, V and Lainscak, M}, title = {Optimizing cardiopulmonary rehabilitation of long COVID-19 syndrome: are we there yet?.}, journal = {European journal of preventive cardiology}, volume = {29}, number = {8}, pages = {e268-e269}, doi = {10.1093/eurjpc/zwac038}, pmid = {35188188}, issn = {2047-4881}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35185603, year = {2021}, author = {Pozzi, A}, title = {COVID-19 and Mitochondrial Non-Coding RNAs: New Insights From Published Data.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {805005}, pmid = {35185603}, issn = {1664-042X}, abstract = {Scientists all around the world are working to investigate new ways to prevent and treat COVID-19, and recent research has been focusing on the effects of a syndrome commonly called "long COVID." People affected by this syndrome usually suffer from symptoms like the ones observed in several types of fatigue syndrome. As these syndromes are often linked to mitochondrial dysfunction, researchers hypothesized that a dysfunction in the mitochondrial metabolism might be part of the causes of long COVID. However, while there are a few studies investigating the effect of SARS-CoV-2 infection on mitochondrial metabolism, the effect on the transcription of mitochondrial non-coding RNAs has not been investigated yet. Thus, using publicly available data, I explored the effect of SARS-CoV-2 on the expression of several mitochondrial non-coding RNAs in patients recovering from COVID-19. No change in the expression of long non-coding RNAs was detected at any stage of the infection, but up to 43 small mitochondrial RNAs have their expression altered during the recovery from COVID-19. This result suggests that the SARS-CoV-2 infection somehow affected the metabolism of small mitochondrial RNAs specifically without altering the overall mitochondrial transcription. Despite these being only preliminary results on a small cohort, the analyses clearly showed that individuals infected by SARS-CoV-2 retain an altered expression of these small RNAs. This persistent alteration in the expression of small mitochondrial RNAs might be involved in the long COVID syndrome and further studies are needed to confirm the possibility.}, } @article {pmid35182777, year = {2022}, author = {Dotan, A and David, P and Arnheim, D and Shoenfeld, Y}, title = {The autonomic aspects of the post-COVID19 syndrome.}, journal = {Autoimmunity reviews}, volume = {21}, number = {5}, pages = {103071}, pmid = {35182777}, issn = {1873-0183}, mesh = {Autonomic Nervous System ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 outbreak, responsible for the widespread COVID-19, led to one of the most rogue pandemics in modern time, yet the major effects of the pandemic may still be ahead of us. SARS-CoV-2 had been found to possess autoimmune properties. Close to 20 distinct autoantibodies which target GPCR of the nervous system and renin-angiotensin system-related molecules were found significantly associated with the clinical severity of COVID-19. The new on-set of more than 10 various autoimmune disorders were documented as well. Additionally, clinical presentations of persisted symptoms were triggered in numerous recently recovered COVID-19 patients, which led to the formulation of the novel term "post-COVID19 syndrome". Manifestations related to post-COVID-19 syndrome exist among approximately 50-80% of symptomatic COVID-19 patients who recovered, and among patients reported more than 50 different long-term effects of the SARS-CoV-2 infection. Many of the common symptoms of the post-COVID19 syndrome are not explained by the virus-related injury alone. Similarly to chronic fatigue syndrome and fibromyalgia, autoimmune-mediated autonomic nervous system dysfunction may play a significant part in the pathogenesis of such symptoms, including chronic fatigue, cognitive impairment, mood related disorders, and numerous more. Importantly, therapeutic options such as immunomodulatory and immunosuppressive therapy may favor some post-COVID19 patients, while plasmapheresis and IVIG could be considered in severe cases. Nevertheless, as physical exercise has been found to stabilize the autonomic nervous system, exercise therapy might be a safer and more effective remedy for the post-COVID19 syndrome.}, } @article {pmid35182760, year = {2022}, author = {Yelin, D and Moschopoulos, CD and Margalit, I and Gkrania-Klotsas, E and Landi, F and Stahl, JP and Yahav, D}, title = {ESCMID rapid guidelines for assessment and management of long COVID.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {7}, pages = {955-972}, pmid = {35182760}, issn = {1469-0691}, mesh = {*COVID-19/complications/diagnosis/therapy ; Evidence-Based Medicine ; Humans ; Quality of Life ; Recovery of Function ; Return to Work ; Post-Acute COVID-19 Syndrome ; }, abstract = {SCOPE: The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'.

METHODS: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design.

RECOMMENDATIONS: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19.}, } @article {pmid35177935, year = {2022}, author = {Duerlund, LS and Shakar, S and Nielsen, H and Bodilsen, J}, title = {Positive Predictive Value of the ICD-10 Diagnosis Code for Long-COVID.}, journal = {Clinical epidemiology}, volume = {14}, number = {}, pages = {141-148}, pmid = {35177935}, issn = {1179-1349}, abstract = {PURPOSE: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for long coronavirus disease 2019 (long-COVID) in a Danish Health registry.

PATIENTS AND METHODS: This was a medical record review of all patients with a diagnosis code of long-COVID (DB948A) at all hospitals in the North Denmark Region from February 27, 2020 through June 30, 2021. Confirmed long-COVID was categorized as fulfillment of all three criteria: (1) a positive polymerase chain reaction (PCR) test for SARS-CoV-2 on a respiratory sample or a positive serum antibody test, (2) symptoms suggestive of long-COVID with no other diagnosis considered more likely, and (3) symptom duration >6 weeks.

RESULTS: A total of 306 patients were assigned a hospital diagnosis code for long-COVID corresponding to 1.4% of all SARS-CoV-2 positive individuals during the study period (n=21,727). Next, 40 patients were excluded due to incomplete diagnostic evaluation at time of record review leaving 266 patients for analysis. The patients had a median age of 51 years (interquartile range 43-60) and 175/266 (66%) were females. Long-COVID was confirmed in 249/266 yielding an overall PPV of 94% (95%CI: 90-96) and did not differ substantially according to most age groups, sex, previous hospitalization for COVID-19, or by using 12 weeks of symptom duration as cut-off. The PPV was low for children and adolescents (n=5), the very elderly (n=9), and those included by secondary long-COVID diagnoses (n=10).

CONCLUSION: The overall PPV of diagnosis codes for long-COVID in the North Denmark Region was high and was likely suitable for future registry-based studies of long-COVID. Caution is advised at the extremes of age and secondary diagnosis codes.}, } @article {pmid35176758, year = {2022}, author = {Raman, B and Bluemke, DA and Lüscher, TF and Neubauer, S}, title = {Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus.}, journal = {European heart journal}, volume = {43}, number = {11}, pages = {1157-1172}, pmid = {35176758}, issn = {1522-9645}, support = {//National Institute for Health Research/ ; //Oxford Biomedical Research Centre/ ; RE/18/3/34214//Oxford British Heart Foundation (BHF) Centre of Research Excellence/ ; }, mesh = {*COVID-19/complications ; *Heart Diseases ; Humans ; *Myocarditis/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.}, } @article {pmid35174650, year = {2022}, author = {Clark, IA}, title = {Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic.}, journal = {Pharmacology research & perspectives}, volume = {10}, number = {2}, pages = {e00926}, pmid = {35174650}, issn = {2052-1707}, mesh = {COVID-19/*complications/metabolism/pathology ; Etanercept/administration & dosage/*therapeutic use ; Humans ; Injections, Spinal ; Microglia/metabolism/pathology ; Stroke/*complications/metabolism ; Syndrome ; Tumor Necrosis Factor-alpha/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {The chronic neurological aspects of traumatic brain injury, post-stroke syndromes, long COVID-19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen-associated molecular patterns or damage-associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non-infectious conditions. The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF-maintained, microglial activation. While too large to negotiate the blood-brain barrier effectively, the specific anti-TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.}, } @article {pmid35172970, year = {2022}, author = {Mahase, E}, title = {Covid-19: Vaccinated people are less likely to get long covid, review finds.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o407}, doi = {10.1136/bmj.o407}, pmid = {35172970}, issn = {1756-1833}, } @article {pmid35172609, year = {2022}, author = {Almomen, A and Cox, J and Lebouché, B and Cheng, MP and Frenette, C and Routy, JP and Costiniuk, CT}, title = {Short Communication: Ongoing Impact of the Social Determinants of Health During the Second and Third Waves of the COVID-19 Pandemic in People Living with HIV Receiving Care in a Montreal-Based Tertiary Care Center.}, journal = {AIDS research and human retroviruses}, volume = {38}, number = {5}, pages = {359-362}, doi = {10.1089/AID.2021.0186}, pmid = {35172609}, issn = {1931-8405}, support = {//CIHR/Canada ; }, mesh = {*COVID-19/complications/epidemiology ; *HIV Infections/complications/epidemiology ; Humans ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; Social Determinants of Health ; Tertiary Care Centers ; Post-Acute COVID-19 Syndrome ; }, abstract = {We performed retrospective chart reviews and described the clinical characteristics, exposure risks, and disease severity of people living with HIV (PLWH) attending the Chronic Viral Illness Service (CVIS) in Montreal, Canada, who developed coronavirus disease 2019 (COVID-19) during September 2020-August 2021, coinciding with the second and third waves of the pandemic. A total of 61 PLWH with a positive COVID-19 polymerase chain reaction were identified, giving a COVID-19 prevalence of 5%. The most common exposure risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during waves two and three was having a family member/close contact with COVID-19 (36%). Similar to what we observed during the first wave, PLWH who acquired COVID-19 during waves two and three of the pandemic often worked or lived in long-term care residences or health care settings, putting them at risk. Five people (8%) were asymptomatic. Nearly all persons had mild disease on initial presentation and most had a full recovery. Two individuals were admitted to hospital with COVID-19, whereas three individuals acquired COVID-19 nosocomially. No individuals died due to COVID-19. Two individuals developed symptoms associated with long COVID-19 syndrome. Findings highlight the ongoing impact of the social determinants of health during the second and third waves of the pandemic in PLWH.}, } @article {pmid35169790, year = {2022}, author = {Aghaei, A and Zhang, R and Taylor, S and Tam, CC and Yang, CH and Li, X and Qiao, S}, title = {Impact of COVID-19 symptoms on social aspects of life among female long haulers: A qualitative study.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {35169790}, issn = {2693-5015}, support = {R01 AI127203/AI/NIAID NIH HHS/United States ; }, abstract = {INTRODUCTION: Persistent COVID-19 symptoms (long COVID) may bring numerous challenges to long haulers' social lives. Women may have to endure more profound impacts given their social roles and existing structural inequality. This study aims to explore the impacts of long COVID on various aspects of social life among female long haulers.

METHODS: We conducted 15 semi-structured interviews with female long haulers in the United States purposely recruited from Facebook groups, Slack group, and organization websites. The interviews were audio recorded after appropriate consent and transcribed verbatim. Inductive approach was applied in thematic analysis, which consists of six stages: becoming familiar with data, developing initial codes, extracting themes, refining themes, labeling themes, and reporting. The MAXQDA software was used in data analysis.

RESULTS: Participants reported persistent symptoms that negatively affected their social lives in many ways. The main impacts included physical limitation, financial hardship, social relationship, conflict of social roles, and social stigma. Negative effects of long COVID hindered female long haulers' recovery process. Social isolation, COVID-19 associated stigma, and conflicts of social roles cause tremendous stress. Employers' support and social media usage may play positive role in their coping with impacts of long COVID on their social life.

CONCLUSION: Existing policies and intervention programs need to be adapted to address the challenges and barriers that long haulers face in returning to normal social life, especially for females. Tailored social life-related recommendations and social support are needed for female long haulers.}, } @article {pmid35169700, year = {2022}, author = {Badenoch, JB and Rengasamy, ER and Watson, C and Jansen, K and Chakraborty, S and Sundaram, RD and Hafeez, D and Burchill, E and Saini, A and Thomas, L and Cross, B and Hunt, CK and Conti, I and Ralovska, S and Hussain, Z and Butler, M and Pollak, TA and Koychev, I and Michael, BD and Holling, H and Nicholson, TR and Rogers, JP and Rooney, AG}, title = {Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis.}, journal = {Brain communications}, volume = {4}, number = {1}, pages = {fcab297}, pmid = {35169700}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/J000914/1/MRC_/Medical Research Council/United Kingdom ; MRF_C0396/MRF/MRF/United Kingdom ; }, abstract = {The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I [2]. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I [2 ]= 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.}, } @article {pmid35169377, year = {2021}, author = {Salihefendic, N and Zildzic, M and Huseinagic, H}, title = {Ischemic Vasculitis as a Cause of Brain Disorder's in Patients with Long Covid: Case Report.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {75}, number = {6}, pages = {471-474}, pmid = {35169377}, issn = {1986-5961}, mesh = {Brain ; *Brain Diseases/etiology ; *COVID-19/complications ; Female ; Humans ; SARS-CoV-2 ; *Vasculitis/complications ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The new coronavirus SARS-CoV-2 caused a pandemic that threatened all aspects of life and health while worsening the socio-economic situation of the entire population. COVID-19 affects all organs and organ systems. The symptoms of the affected organs can last for a long time after the acute infection. About 1/3 of patients develop neuropsychiatric signs in the clinical course of the disease. The most common symptoms are mental fog, headache, cognitive changes, behavior changes, muscle weakness, anosmia and ageusia. These symptoms may develop due to a direct effect of the virus on the neurons or hyper reactive immune response.

OBJECTIVE: The aim of this article is to describe 2 young adults who developed neuropsychiatric symptoms in the course of Long COVID-19 syndrome. Ischemic vasculitis was proved using CT imaging.

CASE REPORT: We collected data of two younger females who had previously recovered from the acute form of COVID-19 without respiratory complications. They developed in the next 1-2 months a clinical picture of a brain disorder. In both cases, CT and angiography scans of the brain showed signs of ischemic vasculitis. Neurological therapy has led to an improvement of the neuropsychiatric symptoms.

CONCLUSION: Neuropsychiatric disorders in Long Covid syndrome are common and diverse. Two cases of young adults who developed signs of neurological disorder in the post COVID-19 period were presented, and CT scans of the brain showed signs of ischemic vasculitis.}, } @article {pmid35169259, year = {2022}, author = {Alwan, NA}, title = {Lessons from Long COVID: working with patients to design better research.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {4}, pages = {201-202}, pmid = {35169259}, issn = {1474-1741}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The perspectives of people with lived experience of any condition being researched must actively inform the research questions asked and the way in which we go about answering them. The experience of Long Covid gives a contemporary example of how working together with patients is integral to medical research.}, } @article {pmid35169258, year = {2022}, author = {Flemming, A}, title = {First glimpses into the mechanisms of Long COVID.}, journal = {Nature reviews. Immunology}, volume = {22}, number = {3}, pages = {146}, pmid = {35169258}, issn = {1474-1741}, } @article {pmid35168680, year = {2022}, author = {Bhaiyat, AM and Sasson, E and Wang, Z and Khairy, S and Ginzarly, M and Qureshi, U and Fikree, M and Efrati, S}, title = {Hyperbaric oxygen treatment for long coronavirus disease-19: a case report.}, journal = {Journal of medical case reports}, volume = {16}, number = {1}, pages = {80}, pmid = {35168680}, issn = {1752-1947}, mesh = {*COVID-19/complications ; Diffusion Tensor Imaging ; Humans ; *Hyperbaric Oxygenation ; Male ; Middle Aged ; Oxygen ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as "long COVID." Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy.

CASE PRESENTATION: A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity.

CONCLUSIONS: We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.}, } @article {pmid35165652, year = {2021}, author = {Mughal, F and Khunti, K and Mallen, CD}, title = {The impact of COVID-19 on primary care: Insights from the National Health Service (NHS) and future recommendations.}, journal = {Journal of family medicine and primary care}, volume = {10}, number = {12}, pages = {4345}, pmid = {35165652}, issn = {2249-4863}, support = {NIHR300957/DH_/Department of Health/United Kingdom ; }, abstract = {COVID-19 has changed health systems and services. In this commentary, we outline the impact COVID-19 has had on the delivery of primary health care, and on primary care teams, and describe the NHS response. We highlight the challenges of managing long-COVID and identify areas of importance for primary care in a post-COVID context. We describe ongoing public health measures and list recommendations for primary care for COVID-19 and future unknown pandemics. We conclude with salient points on the future of primary care.}, } @article {pmid35164920, year = {2022}, author = {Ludot, M and Breton, S and Ibrahim, N and Moro, MR}, title = {[A case of long form Covid-19 reported by a suffering teenager].}, journal = {Soins. Pediatrie, puericulture}, volume = {43}, number = {324}, pages = {12-14}, doi = {10.1016/j.spp.2021.12.003}, pmid = {35164920}, issn = {1259-4792}, mesh = {Adolescent ; Anxiety ; *COVID-19 ; Depression ; Humans ; SARS-CoV-2 ; }, abstract = {Long-term Covid-19 is now part of our lives and can be questioned by adolescents and their families when faced with long- lasting and unexplained symptoms. This is the case of Alice, a 16-year-old teenager treated at the Cochin Hospital's adolescent centre, who presents digestive disorders and strange body sensations mas-king anxiety-depressive affects.}, } @article {pmid35164631, year = {2022}, author = {Miguez-Rey, E and Choi, D and Kim, S and Yoon, S and Săndulescu, O}, title = {Monoclonal antibody therapies in the management of SARS-CoV-2 infection.}, journal = {Expert opinion on investigational drugs}, volume = {31}, number = {1}, pages = {41-58}, pmid = {35164631}, issn = {1744-7658}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Neutralizing antibodies (NAbs) that target key domains of the spike protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have therapeutic value because of their specificity. Depending on the targeted epitope, single agents may be effective, but combined treatment involving multiple NAbs may be necessary to prevent the emergence of resistant variants.

AREAS COVERED: This article highlights the accelerated regulatory processes established to facilitate the review and approval of potential therapies. An overview of treatment approaches for SARS-CoV-2 infection, with detailed examination of the preclinical and clinical evidence supporting the use of NAbs, is provided. Finally, insights are offered into the potential benefits and challenges associated with the use of these agents.

EXPERT OPINION: NAbs offer an effective, evidence-based therapeutic intervention during the early stages of SARS-CoV-2 infection when viral replication is the primary factor driving disease progression. As the pandemic progresses, appropriate use of NAbs will be important to minimize the risk of escape variants. Ultimately, the availability of effective treatments for COVID-19 will allow the establishment of treatment algorithms for minimizing the substantial rates of hospitalization, morbidity (including long COVID) and mortality currently associated with the disease.}, } @article {pmid35162225, year = {2022}, author = {Sojka, A and Machniak, M and Andrzejewski, W and Kosendiak, A and Chwałczyńska, A}, title = {Changes in Physical Activity and the Occurrence of Specific Symptoms of "Long-COVID Syndrome" in Men Aged 18-25.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {3}, pages = {}, pmid = {35162225}, issn = {1660-4601}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Exercise ; Humans ; Male ; Pandemics ; SARS-CoV-2 ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {The aim of this study was to assess the occurrence of non-specific symptoms of "long-COVID syndrome" depending on the physical activity undertaken resulting from the imposed forms of study (distance learning-contact learning); 136 men aged 21.5 ± 1.58 from universities educating students of medical faculties were examined. The difference between the universities was mainly due to the nature of the classes undertaken (classes remotely-hybrid form) in the period from March 2020 to February 2021. Among the respondents, 17% in Group I and 16% in Group II were infected with the SARS-CoV-2 virus, including 50% in Group I with moderate symptoms, and in Group II-most people 45% with mild symptoms. The conducted research clearly shows the impact of the COVID-19 pandemic on students. They show a number of important problems, such as reduced physical activity, as well as increased body weight and time spent in front of the monitor. They also make it clear that the health consequences of the pandemic affect both people who were infected with the SARS-CoV-2 virus and those who did not suffer from this infection.}, } @article {pmid35160024, year = {2022}, author = {Jones, OY and Yeralan, S}, title = {Is Long COVID a State of Systemic Pericyte Disarray?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {3}, pages = {}, pmid = {35160024}, issn = {2077-0383}, support = {XXX//Eleanor Naylor Dana Charitable Trust/ ; }, abstract = {The most challenging aspect of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) or Long COVID remains for the discordance between the viral damage from acute infection in the recent past and susceptibility of Long COVID without clear evidence of post infectious inflammation or autoimmune reactions. In this communication we propose that disarray of pericytes plays a central role in emerge of Long COVID. We assume pericytes are agents with "Triple-A" qualities, i.e., analyze-adapt and advance, necessary for sustainability of host homeostasis. Based on this view, we further suggest Long COVID may provide a model system to integrate system theory and complex adaptive systems to explore a new class of maladies those are currently not well defined and with no remedies.}, } @article {pmid35159974, year = {2022}, author = {Visco, V and Vitale, C and Rispoli, A and Izzo, C and Virtuoso, N and Ferruzzi, GJ and Santopietro, M and Melfi, A and Rusciano, MR and Maglio, A and Di Pietro, P and Carrizzo, A and Galasso, G and Vatrella, A and Vecchione, C and Ciccarelli, M}, title = {Post-COVID-19 Syndrome: Involvement and Interactions between Respiratory, Cardiovascular and Nervous Systems.}, journal = {Journal of clinical medicine}, volume = {11}, number = {3}, pages = {}, pmid = {35159974}, issn = {2077-0383}, abstract = {Though the acute effects of SARS-CoV-2 infection have been extensively reported, the long-term effects are less well described. Specifically, while clinicians endure to battle COVID-19, we also need to develop broad strategies to manage post-COVID-19 symptoms and encourage those affected to seek suitable care. This review addresses the possible involvement of the lung, heart and brain in post-viral syndromes and describes suggested management of post-COVID-19 syndrome. Post-COVID-19 respiratory manifestations comprise coughing and shortness of breath. Furthermore, arrhythmias, palpitations, hypotension, increased heart rate, venous thromboembolic diseases, myocarditis and acute heart failure are usual cardiovascular events. Among neurological manifestations, headache, peripheral neuropathy symptoms, memory issues, lack of concentration and sleep disorders are most commonly observed with varying frequencies. Finally, mental health issues affecting mental abilities and mood fluctuations, namely anxiety and depression, are frequently seen. Finally, long COVID is a complex syndrome with protracted heterogeneous symptoms, and patients who experience post-COVID-19 sequelae require personalized treatment as well as ongoing support.}, } @article {pmid35158380, year = {2022}, author = {Michler, E and Dolzhenko, Y and Altmann, C}, title = {[Late neurological consequences of a SARS-CoV-2 infection].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {147}, number = {4}, pages = {173-177}, doi = {10.1055/a-1689-6188}, pmid = {35158380}, issn = {1439-4413}, mesh = {COVID-19/*complications ; Humans ; Male ; Middle Aged ; Nervous System Diseases/diagnosis/*etiology/*rehabilitation ; Occupational Therapy/methods ; Physical Therapy Modalities ; Psychosocial Support Systems ; *SARS-CoV-2 ; }, abstract = {BACKGROUND: Persistent neurological late symptoms of SARS-CoV-2 infection are common and require regular follow-up treatment. In order to establish uniform therapy concepts, it is necessary to evaluate individual therapeutic approaches for long COVID and post-COVID-19 syndrome.

ANAMNESE: A 62-year-old patient was admitted to our rehab clinic for follow-up treatment after severe SARS-CoV-2 infection with neurological symptoms. The initially extensive laboratory and imaging investigation did not reveal any organic cause for the sometimes apoplectiform, complex clinical picture, so that the patient was transferred directly to our rehabilitation clinic in the event of everyday restrictions and rollator dependency.

EXAMINATION AND FINDINGS: Clinically, there was a reduced general condition and the mood was depressed. Neurological symptoms were gait ataxia, hand tremor, amnesic aphasia and reduced ability to concentrate. PET / CT showed no evidence of tumor or inflammation.

THERAPY AND PROGRESS: A multimodal therapy program consisting of physiotherapy and occupational therapy as well as psychological support was carried out. In addition, off-label therapy with oral glucocorticoids and colchicine was initiated. In the course of the disease, there was a clear reduction in all symptoms with little residual hand tremor.

CONCLUSIONS: Whole body and brain FDG PET can be helpful in long COVID and post-COVID-19 syndrome patients with neurological symptoms of unknown origin. These patients benefit from systematic rehabilitation. Glucocorticoids and colchicine appear to accelerate symptom reduction. The rehabilitative therapy should be continued on an outpatient basis.}, } @article {pmid35158095, year = {2022}, author = {Seang, S and Itani, O and Monsel, G and Abdi, B and Marcelin, AG and Valantin, MA and Palich, R and Fayçal, A and Pourcher, V and Katlama, C and Tubiana, R}, title = {Long COVID-19 symptoms: Clinical characteristics and recovery rate among non-severe outpatients over a six-month follow-up.}, journal = {Infectious diseases now}, volume = {52}, number = {3}, pages = {165-169}, pmid = {35158095}, issn = {2666-9919}, mesh = {Asthenia ; *COVID-19/complications ; Dyspnea ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myalgia ; Outpatients ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: To describe persistent symptoms in long COVID-19 non-severe outpatients and report the 6-month clinical recovery (CR) rate.

METHODS: Observational study enrolling outpatients (≥ 18 years) with confirmed non-severe COVID-19 (positive nasopharyngeal RT-PCR or presence of SARS-CoV-2 antibodies) who consulted for persistent symptoms after the first pandemic wave (March-May 2020). CR was assessed at the 6-month visit and defined as complete (no symptom), partial (persistent symptoms of lower intensity) or lack of recovery (no improvement).

RESULTS: Sixty-three patients (79% women, mean age: 48 years) enrolled; main symptoms (mean 81 days after acute infection): asthenia/myalgia (77%), dyspnea (51%), headaches (35%), cough (33%). At 6 months (n=56), 30% had complete, 57% partial, and 13% lack of recovery. The proportion of patients with>2 persistent symptoms was 26% at 6 months (main symptoms: dyspnea [54%] and asthenia/myalgia [46%]).

CONCLUSION: We observed a slow but high recovery rate at 6 months among these outpatients.}, } @article {pmid35155749, year = {2022}, author = {Calabrese, L and Colloca, L}, title = {Long COVID-19 and the Role of the Patient-Clinician Interaction in Symptom Management.}, journal = {Journal of patient experience}, volume = {9}, number = {}, pages = {23743735221077514}, pmid = {35155749}, issn = {2374-3735}, } @article {pmid35155636, year = {2022}, author = {Bisceglia, I and Canale, ML and Gallucci, G and Turazza, FM and Lestuzzi, C and Parrini, I and Russo, G and Maurea, N and Quagliariello, V and Oliva, S and Di Fusco, SA and Lucà, F and Tarantini, L and Trambaiolo, P and Moreo, A and Geraci, G and Gabrielli, D and Gulizia, MM and Oliva, F and Colivicchi, F}, title = {Cardio-Oncology in the COVID Era (Co & Co): The Never Ending Story.}, journal = {Frontiers in cardiovascular medicine}, volume = {9}, number = {}, pages = {821193}, pmid = {35155636}, issn = {2297-055X}, abstract = {The pathophysiology of some non-communicable diseases (NCDs) such as hypertension, cardiovascular disease (CVD), diabetes, and cancer includes an alteration of the endothelial function. COVID-19 is a pulmonary and vascular disease with a negative impact on patients whose damaged endothelium is particularly vulnerable. The peculiar SARS-CoV-2-induced "endothelitis" triggers an intriguing immune-thrombosis that affects both the venous and arterial vascular beds. An increased liability for infection and an increased likelihood of a worse outcome have been observed during the pandemic in patients with active cancer and in cancer survivors. "Overlapping commonalities" between COVID-19 and Cardio-Oncology have been described that include shared phenotypes of cardiovascular toxicities such as left ventricular dysfunction, ischemic syndromes, conduction disturbances, myocarditis, pericarditis and right ventricular failure; shared pathophysiologic mechanisms such as inflammation, release of cytokines, the renin-angiotensin-aldosterone-pathway, coagulation abnormalities, microthrombosis and endothelial dysfunction. For these features and for the catalyst role of NCDs (mainly CVD and cancer), we should refer to COVID-19 as a "syndemic." Another challenging issue is the persistence of the symptoms, the so-called "long COVID" whose pathogenesis is still uncertain: it may be due to persistent multi-organ viral attacks or to an abnormal immune response. An intensive vaccination campaign is the most successful pharmacological weapon against SARS-CoV-2, but the increasing number of variants has reduced the efficacy of the vaccines in controlling SARS-CoV-2 infections. After a year of vaccinations we have also learned more about efficacy and side-effects of COVID-19 vaccines. An important byproduct of the COVID-19 pandemic has been the rapid expansion of telemedicine platforms across different care settings; this new modality of monitoring cancer patients may be useful even in a post pandemic era. In this paper we analyze the problems that the cardio-oncologists are facing in a pandemic scenario modified by the extensive vaccination campaign and add actionable recommendations derived from the ongoing studies and from the syndemic nature of the infection.}, } @article {pmid35155571, year = {2021}, author = {Rahimmanesh, I and Shariati, L and Dana, N and Esmaeili, Y and Vaseghi, G and Haghjooy Javanmard, S}, title = {Cancer Occurrence as the Upcoming Complications of COVID-19.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {813175}, pmid = {35155571}, issn = {2296-889X}, abstract = {Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID-19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi-organ failure are hallmarks of severe COVID-19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low-grade inflammation in "long COVID-19" syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.}, } @article {pmid35153987, year = {2021}, author = {Gilio, L and Galifi, G and Centonze, D and Stampanoni Bassi, M}, title = {Case Report: Overlap Between Long COVID and Functional Neurological Disorders.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {811276}, pmid = {35153987}, issn = {1664-2295}, abstract = {Long lasting symptoms have been reported in a considerable proportion of patients after a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. This condition, defined as either "post-acute coronavirus disease (COVID)," "long COVID," or "long-haul COVID," has also been described in outpatients and in individuals who are asymptomatic during the acute infection. A possible overlap exists between this condition and the functional neurological disorders (FNDs). We report a 23-year-old man who developed, after asymptomatic COVID-19, a complex symptomatology characterized by fatigue, episodic shortness of breath, nocturnal tachycardia, and chest pain. He also complained of attention and memory difficulties, fluctuating limb dysesthesia, and weakness of his left arm. After neurological examination, a diagnosis of FND was made. Notably, the patient was also evaluated at a post-COVID center and received a diagnosis of long COVID-19 syndrome. After 4 months of psychoanalytic psychotherapy and targeted physical therapy in our center for FNDs, dysesthesia and motor symptoms had resolved, and the subjective cognitive complaints had improved significantly. However, the patient had not fully recovered as mild symptoms persisted limiting physical activities. Long-term post COVID symptoms and FNDs may share underlying biological mechanisms, such as stress and inflammation. Our case suggests that functional symptoms may coexist with the long COVID symptoms and may improve with targeted interventions. In patients presenting with new fluctuating symptoms after SARS-CoV-2 infection, the diagnosis of FNDs should be considered, and the positive clinical signs should be carefully investigated.}, } @article {pmid35153633, year = {2022}, author = {Pinto, MD and Lambert, N and Downs, CA and Abrahim, H and Hughes, TD and Rahmani, AM and Burton, CW and Chakraborty, R}, title = {Antihistamines for Postacute Sequelae of SARS-CoV-2 Infection.}, journal = {The journal for nurse practitioners : JNP}, volume = {18}, number = {3}, pages = {335-338}, pmid = {35153633}, issn = {1555-4155}, abstract = {Postacute sequelae of SARS-CoV2 (PASC) infection is an emerging global health crisis, variably affecting millions worldwide. PASC has no established treatment. We describe 2 cases of PASC in response to opportune administration of over-the-counter antihistamines, with significant improvement in symptoms and ability to perform activities of daily living. Future studies are warranted to understand the potential role of histamine in the pathogenesis of PASC and explore the clinical benefits of antihistamines in the treatment of PASC.}, } @article {pmid35151371, year = {2022}, author = {Vijayakumar, B and Boustani, K and Ogger, PP and Papadaki, A and Tonkin, J and Orton, CM and Ghai, P and Suveizdyte, K and Hewitt, RJ and Desai, SR and Devaraj, A and Snelgrove, RJ and Molyneaux, PL and Garner, JL and Peters, JE and Shah, PL and Lloyd, CM and Harker, JA}, title = {Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.}, journal = {Immunity}, volume = {55}, number = {3}, pages = {542-556.e5}, pmid = {35151371}, issn = {1097-4180}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/S004068/2/MRC_/Medical Research Council/United Kingdom ; MR/V027638/1/MRC_/Medical Research Council/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; B-Lymphocytes/*immunology ; COVID-19/complications/*immunology ; Female ; Follow-Up Studies ; Humans ; Immunity, Cellular ; Immunoproteins ; Male ; Middle Aged ; Monocytes/*immunology ; Proteome ; Respiration Disorders/etiology/*immunology ; Respiratory System/*immunology/pathology ; SARS-CoV-2/*physiology ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.}, } @article {pmid35150911, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Rodríguez-Jiménez, J and Pellicer-Valero, OJ}, title = {Exploring the trajectory recovery curve of the number of post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {117}, number = {}, pages = {201-203}, pmid = {35150911}, issn = {1878-3511}, mesh = {*COVID-19/complications ; Hospitalization ; Hospitals ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: This multicenter study investigated the recovery curve of the number of post-COVID-19 symptoms in previously hospitalized patients using an exponential decay model and mosaic plots.

METHODS: Patients hospitalized during the first wave of the pandemic (from March 10, 2010-May 31, 2020) due to COVID-19 from 5 hospitals in Madrid, Spain were scheduled for 2 telephone interviews at 2 follow-ups with a 5-month period in between and were asked about the presence of post-COVID-19 symptoms. The total number of post-COVID-19 symptoms was monitored. Clinical features, symptoms at hospital admission, and hospitalization data were collected from medical records.

RESULTS: A total of 1593 patients who had COVID-19 were assessed 8.4 (T1) and 13.2 (T2) months after hospitalization. The mean number of post-COVID-19 symptoms was 2.6 (SD 2.0) at T1 and 1.5 (SD 1.4) at T2. The trajectory curve showed a decrease in prevalence trend. The analysis also revealed that 985 (61.8%) subjects reported more (T1>T2), 549 (34.5%) equal (T1 = T2), and 59 (3.7%) fewer (T1
CONCLUSIONS: Current trajectory analysis revealed an overall decrease in the tendency in the number of post-COVID-19 symptoms throughout the 2 years after the infection.}, } @article {pmid35150765, year = {2022}, author = {Righi, E and Mirandola, M and Mazzaferri, F and Dossi, G and Razzaboni, E and Zaffagnini, A and Ivaldi, F and Visentin, A and Lambertenghi, L and Arena, C and Micheletto, C and Gibellini, D and Tacconelli, E}, title = {Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study.}, journal = {The Journal of infection}, volume = {84}, number = {4}, pages = {566-572}, pmid = {35150765}, issn = {1532-2742}, mesh = {*COVID-19/complications/epidemiology ; Cohort Studies ; Fatigue/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients.

METHODS: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed.

RESULTS: 465 patients (54% males, 51% hospitalized) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalization and ICU stay vs. non-hospitalized status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress.

CONCLUSIONS: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.}, } @article {pmid35149572, year = {2022}, author = {Callan, C and Ladds, E and Husain, L and Pattinson, K and Greenhalgh, T}, title = {'I can't cope with multiple inputs': a qualitative study of the lived experience of 'brain fog' after COVID-19.}, journal = {BMJ open}, volume = {12}, number = {2}, pages = {e056366}, pmid = {35149572}, issn = {2044-6055}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Brain ; *COVID-19/complications/psychology ; Female ; Humans ; Mental Fatigue/virology ; Qualitative Research ; SARS-CoV-2 ; Somatoform Disorders/*virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To explore the lived experience of 'brain fog'-the wide variety of neurocognitive symptoms that can follow COVID-19.

DESIGN AND SETTING: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.

METHOD: 50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others' accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.

RESULTS: Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term 'brain fog'; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants' search for physical mechanisms to explain their symptoms.

CONCLUSION: These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.}, } @article {pmid35147823, year = {2022}, author = {Drosos, AA and Pelechas, E and Voulgari, PV}, title = {Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?.}, journal = {Clinical rheumatology}, volume = {41}, number = {3}, pages = {957-958}, pmid = {35147823}, issn = {1434-9949}, mesh = {Autoimmunity ; *COVID-19/complications ; Humans ; *Rheumatology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35144991, year = {2022}, author = {Antoniou, KM and Vasarmidi, E and Russell, AM and Andrejak, C and Crestani, B and Delcroix, M and Dinh-Xuan, AT and Poletti, V and Sverzellati, N and Vitacca, M and Witzenrath, M and Tonia, T and Spanevello, A}, title = {European Respiratory Society statement on long COVID follow-up.}, journal = {The European respiratory journal}, volume = {60}, number = {2}, pages = {}, pmid = {35144991}, issn = {1399-3003}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications ; Follow-Up Studies ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Patients diagnosed with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aimed to identify optimal strategies for follow-up care that may positively impact the patient's quality of life (QoL). A European Respiratory Society (ERS) Task Force convened and prioritised eight clinical questions. A targeted search of the literature defined the timeline of "long COVID" as 1-6 months post-infection and identified clinical evidence in the follow-up of patients. Studies meeting the inclusion criteria report an association of characteristics of acute infection with persistent symptoms, thromboembolic events in the follow-up period, and evaluations of pulmonary physiology and imaging. Importantly, this statement reviews QoL consequences, symptom burden, disability and home care follow-up. Overall, the evidence for follow-up care for patients with long COVID is limited.}, } @article {pmid35144718, year = {2022}, author = {Tang, SW and Leonard, BE and Helmeste, DM}, title = {Long COVID, neuropsychiatric disorders, psychotropics, present and future.}, journal = {Acta neuropsychiatrica}, volume = {34}, number = {3}, pages = {109-126}, doi = {10.1017/neu.2022.6}, pmid = {35144718}, issn = {1601-5215}, mesh = {Anxiety ; *COVID-19/complications/epidemiology ; Humans ; Pandemics ; Psychotropic Drugs/therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Long COVID refers to the lingering symptoms which persist or appear after the acute illness. The dominant long COVID symptoms in the two years since the pandemic began (2020-2021) have been depression, anxiety, fatigue, concentration and cognitive impairments with few reports of psychosis. Whether other symptoms will appear later on is not yet known. For example, dopamine-dependent movement disorders generally take many years before first symptoms are seen. Post-stroke depression and anxiety may explain many of the early long COVID cases. Hemorrhagic, hypoxic and inflammatory damages of the central nervous system, unresolved systematic inflammation, metabolic impairment, cerebral vascular accidents such as stroke, hypoxia from pulmonary damages and fibrotic changes are among the major causes of long COVID. Glucose metabolic and hypoxic brain issues likely predispose subjects with pre-existing diabetes, cardiovascular or lung problems to long COVID as well. Preliminary data suggest that psychotropic medications may not be a danger but could instead be beneficial in combating COVID-19 infection. The same is true for diabetes medications such as metformin. Thus, a focus on sigma-1 receptor ligands and glucose metabolism is expected to be useful for new drug development as well as the repurposing of current drugs. The reported protective effects of psychotropics and antihistamines against COVID-19, the earlier reports of reduced number of sigma-1 receptors in post-mortem schizophrenic brains, with many antidepressant and antipsychotic drugs being antihistamines with significant affinity for the sigma-1 receptor, support the role of sigma and histamine receptors in neuroinflammation and viral infections. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.}, } @article {pmid35144461, year = {2022}, author = {Mendelsohn, AS and Nath, N and De Sá, A and Von Pressentin, KB}, title = {Two months follow-up of patients with non-critical COVID-19 in Cape Town, South Africa.}, journal = {South African family practice : official journal of the South African Academy of Family Practice/Primary Care}, volume = {64}, number = {1}, pages = {e1-e6}, pmid = {35144461}, issn = {2078-6204}, mesh = {Adult ; *COVID-19/complications ; Cross-Sectional Studies ; Follow-Up Studies ; Humans ; Retrospective Studies ; SARS-CoV-2 ; South Africa/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Approximately 10% of coronavirus disease 2019 (COVID-19) patients will experience long COVID. There is no study of long COVID in mild COVID-19 patients in South Africa. This study aimed, firstly, to describe the prevalence of long COVID in mild COVID-19 patients in Cape Town, and, secondly, to document the impact of COVID-19 on patients' well-being, work, and their access to long COVID treatment.

METHODS: In this retrospective cross-sectional study, a random sample of adults diagnosed with mild COVID-19 were called two months post-diagnosis. The participants telephonically completed a standardised survey describing their long COVID symptoms, missed workdays, and health-seeking behaviour. Medical records were reviewed for comorbidities, original COVID-19 symptoms, and treatment.

RESULTS: It was found that 60% of patients with mild COVID-19 had ≥ 1 long COVID symptom, while 35% had ≥ 3 ongoing symptoms for two months. Dyspnoea and fatigue were the most common symptoms. The findings revealed that 52% of employed patients missed work and 25% of patients self-reported non-recovery from their COVID-19. Moreover, 24% of patients consulted a clinician for long COVID, but only 7% of patients received long COVID care in the public sector. Of the 17% of patients requiring additional help for long COVID, 56% were interested in assistance by text message or telephonic consultation.

CONCLUSION: Over a half of mild COVID-19 patients experienced at least one long COVID symptom for two months and nearly 20% needed additional medical treatment. Very few patients utilised the public sector for long COVID treatment. There is a great need for long COVID treatment in public healthcare services and patients are receptive to remote care.}, } @article {pmid35143771, year = {2022}, author = {Kikkenborg Berg, S and Dam Nielsen, S and Nygaard, U and Bundgaard, H and Palm, P and Rotvig, C and Vinggaard Christensen, A}, title = {Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {4}, pages = {240-248}, pmid = {35143771}, issn = {2352-4650}, mesh = {Adolescent ; COVID-19/*complications/diagnosis/epidemiology/psychology ; COVID-19 Testing ; Case-Control Studies ; Cross-Sectional Studies ; Denmark/epidemiology ; Female ; Humans ; Male ; Quality of Life ; SARS-CoV-2 ; Schools ; Sick Leave/statistics & numerical data ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Many adolescents have been affected by the COVID-19 pandemic either directly by being infected with the virus or indirectly by lockdowns and restrictions influencing normal living. We aimed to investigate health, including symptoms of long COVID, in adolescents (aged 15-18 years) who tested positive for SARS-CoV-2 compared with a control group.

METHODS: LongCOVIDKidsDK was a national, cross-sectional study carried out in Denmark, which included SARS-CoV-2-positive adolescents and matched controls. All Danish adolescents aged 15-18 years with a positive SARS-CoV-2 test during the period Jan 1, 2020, to July 12, 2021, and a control group matched (1:4) by age and sex were sent a survey from July 20, 2021. Participants had until Sept 15, 2021, to respond. Symptoms associated with COVID-19, school attendance, and health-related quality of life were investigated using ancillary questions and validated questionnaires (Paediatric Quality of Life Inventory [PedsQL] and Children's Somatic Symptoms Inventory-24 [CSSI-24]). Statistical analyses included descriptive statistics and logistic regression. This study is registered at ClinicalTrials.gov, NCT04786353.

FINDINGS: 24 315 adolescents with a positive SARS-CoV-2 test (case group) and 97 257 matched controls were invited to participate. 3013 matched controls were excluded because of suspected SARS-CoV-2 infection. 6630 (27·3%) responded in the case group and 21 640 (22·3%) responded and were eligible to participate in the control group. Across both groups, median age was 17·6 years (IQR 16·4-18·5), 16 277 (57·6%) of 28 270 responders were female, and 11 993 (42·4%) were male. Participants in the case group had greater odds of having at least one long COVID symptom lasting at least 2 months compared with the control group (3159 [61·9%] vs 12 340 [57·0%], odds ratio 1·22 [95% CI 1·15-1·30]; p<0·0001). Participants in the case group reported significantly lower symptom scores (ie, less somatic distress) on the CSSI-24 than in the control group: mean 10·7 (SD 11·4, median 7·0 [IQR 2·0-15·0]) versus 11·9 (10·6, 9·0 [4·0-17·0]; p<0·0001). Participants in the case group had better quality of life scores on the PedsQL than in the control group: physical functioning mean score 88·7 (SD 13·9, median 93·8 [IQR 84·4-100·0]) versus 86·5 (14·3, 90·6 [81·3-96·9]; p<0·0001); emotional functioning 77·1 (20·3, 80·0 [65·0-95·0]) versus 71·7 (21·4, 75·0 [60·0-90·0]; p<0·0001); social functioning 93·1 (12·5, 100·0 [90·0-100·0]) versus 88·4 (16·2, 95·0 [80·0-100·0]; p<0·0001); and school functioning 66·9 (22·5, 65·0 [60·0-85·0]) versus 62·9 (22·1, 65·0 [50·0-80·0]; p<0·0001). More participants in the case group than in the control group reported 16 or more sick days (1205 [18·2%] vs 2518 [11·6%]; p<0·0001) and 16 or more days of school absence (695 [10·5%] vs 1777 [8·2%]; p<0·0001).

INTERPRETATION: Participants with SARS-CoV-2-positive tests had more long-lasting symptoms and sick leave, whereas participants in the control group had more short-lasting symptoms and worse quality of life. Knowledge of long COVID in adolescents is important to guide clinical recognition and management of this condition.

FUNDING: AP Møller and Chastine McKinney Møller Foundation.}, } @article {pmid35143770, year = {2022}, author = {Stephenson, T and Pinto Pereira, SM and Shafran, R and de Stavola, BL and Rojas, N and McOwat, K and Simmons, R and Zavala, M and O'Mahoney, L and Chalder, T and Crawley, E and Ford, TJ and Harnden, A and Heyman, I and Swann, O and Whittaker, E and , and Ladhani, SN}, title = {Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {4}, pages = {230-239}, pmid = {35143770}, issn = {2352-4650}, support = {MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MR/P020372/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; COVID-19/*complications/*diagnosis/*epidemiology/pathology/psychology ; COVID-19 Testing ; Child ; Cohort Studies ; England/epidemiology ; Female ; Humans ; Male ; Polymerase Chain Reaction ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status.

METHODS: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192).

FINDINGS: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health.

INTERPRETATION: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship.

FUNDING: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation.}, } @article {pmid35142947, year = {2022}, author = {Nguyen, NN and Hoang, VT and Dao, TL and Dudouet, P and Eldin, C and Gautret, P}, title = {Clinical patterns of somatic symptoms in patients suffering from post-acute long COVID: a systematic review.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {41}, number = {4}, pages = {515-545}, pmid = {35142947}, issn = {1435-4373}, mesh = {*COVID-19/complications/epidemiology ; Fatigue/epidemiology/etiology ; Female ; Humans ; *Medically Unexplained Symptoms ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID-19 may affect patients after hospital discharge.

AIMS: This study aims to describe the burden of the long-term persistence of clinical symptoms in COVID-19 patients.

METHODS: We conducted a systematic review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. The PubMed and Google Scholar databases were searched for studies that included information on the prevalence of somatic clinical symptoms lasting at least 4 weeks after the onset of a PCR- or serology-confirmed diagnosis of COVID-19. The prevalence of persisting clinical symptoms was assessed and risk factors were described when investigated. Psychological symptoms and cognitive disorders were not evaluated in this study.

RESULTS: Thirty-seven articles met the inclusion criteria. Eighteen studies involved in-patients only with a duration of follow-up of either less than 12 weeks, 12 weeks to 6 months, or more. In these studies, fatigue (16-64%), dyspnea (15-61%), cough (2-59%), arthralgia (8-55%), and thoracic pain (5-62%) were the most frequent persisting symptoms. In nineteen studies conducted in a majority of out-patients, the persistence of these symptoms was lower and 3% to 74% of patients reported prolonged smell and taste disorders. The main risk factors for persisting symptoms were being female, older, having comorbidities and severity at the acute phase of the disease.

CONCLUSION: COVID-19 patients should have access to dedicated multidisciplinary healthcare allowing a holistic approach. Effective outpatient care for patients with long-COVID-19 requires coordination across multiple sub-specialties, which can be proposed in specialized post-COVID units.}, } @article {pmid35142247, year = {2022}, author = {Martelletti, P and Bentivegna, E}, title = {Insights into headache 2022.}, journal = {Expert review of neurotherapeutics}, volume = {22}, number = {2}, pages = {85-87}, doi = {10.1080/14737175.2022.2038135}, pmid = {35142247}, issn = {1744-8360}, mesh = {*Calcitonin Gene-Related Peptide Receptor Antagonists ; *Headache/therapy ; Humans ; }, } @article {pmid35139906, year = {2022}, author = {Mera-Cordero, F and Bonet-Monne, S and Almeda-Ortega, J and García-Sangenís, A and Cunillera-Puèrtolas, O and Contreras-Martos, S and Alvarez-Muñoz, G and Monfà, R and Balanzó-Joué, M and Morros, R and Salvador-Gonzalez, B}, title = {Correction to: Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol.}, journal = {Trials}, volume = {23}, number = {1}, pages = {130}, pmid = {35139906}, issn = {1745-6215}, } @article {pmid35138737, year = {2022}, author = {Franssen, FME and Janssen, DJA and Spruit, MA}, title = {[Long COVID: the next challenge for health care].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {166}, number = {}, pages = {}, pmid = {35138737}, issn = {1876-8784}, mesh = {*COVID-19/complications ; Delivery of Health Care ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is seen in a growing group of patients who experience a large number of symptoms after previous infection with SARS-CoV-2. The symptoms persist and are accompanied by impaired functioning without a sufficient pathophysiological explanation. While the condition is more commonly seen in patients who have been critically ill, predictive factors for long COVID are lacking. There are also no objective, diagnostic criteria, evidence-based interventions or scientifically based advice for the follow-up of this group. Recent research shows that most symptoms and limitations diminish over time, but also that there is a small group with permanent physical, psychological and/or cognitive problems. This article describes the current definition, epidemiology, and symptoms of long COVID. The functional and structural abnormalities and additional health risks are also discussed. Finally, it mentions a number of challenges that will have to be addressed to prevent this condition from having adverse consequences not only for individual patients but also casting a large shadow on health care and economic recovery.}, } @article {pmid35137496, year = {2022}, author = {Taga, A and Lauria, G}, title = {COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era.}, journal = {Journal of the peripheral nervous system : JPNS}, volume = {27}, number = {1}, pages = {4-30}, pmid = {35137496}, issn = {1529-8027}, mesh = {*COVID-19/complications/epidemiology/prevention & control ; COVID-19 Vaccines/adverse effects ; *Guillain-Barre Syndrome/epidemiology/etiology ; Humans ; Pandemics ; Peripheral Nervous System ; }, abstract = {Increasing literature has linked COVID-19 to peripheral nervous system (PNS) diseases. In addition, as we move from the pandemic to the vaccination era, literature interest is shifting towards the potential association between COVID-19 vaccines and PNS manifestations. We reviewed published literature on COVID-19, COVID-19 vaccines and PNS manifestations between 1 January 2020 and 1 December 2021. For Guillain-Barré syndrome (GBS), isolated cranial neuropathy (ICN) and myositis associated with COVID-19, the demographic, clinical, laboratory, electrophysiological and imaging features were included in a narrative synthesis. We identified 169 studies on COVID-19-associated complications, including 63 papers (92 patients) on GBS, 29 papers (37 patients) on ICN and 11 papers (18 patients) on myositis. Additional clinical phenotypes included chronic inflammatory demyelinating polyneuropathy, vasculitic neuropathies, neuralgic amyotrophy, critical care-related complications, and myasthenia gravis. PNS complications secondary to COVID-19 vaccines have been reported during randomized clinical trials, in real-world case reports, and during large-scale surveillance programs. These mainly include cases of GBS, Bell's palsy, and cases of neuralgic amyotrophy. Based on our extensive review of the literature, any conclusion about a pathophysiological correlation between COVID-19 and PNS disorders remains premature, and solely supported by their temporal association, while epidemiological and pathological data are insufficient. The occurrence of PNS complications after COVID-19 vaccines seems limited to a possible higher risk of facial nerve palsy and GBS, to a degree that widespread access to the ongoing vaccination campaign should not be discouraged, while awaiting for more definitive data from large-scale surveillance studies.}, } @article {pmid35136912, year = {2022}, author = {Krishnan, K and Miller, AK and Reiter, K and Bonner-Jackson, A}, title = {Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19.}, journal = {Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists}, volume = {37}, number = {4}, pages = {729-737}, pmid = {35136912}, issn = {1873-5843}, mesh = {*COVID-19/complications ; Cognition ; *Cognition Disorders/complications/etiology ; Fatigue ; Female ; Humans ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.

METHODS: Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.

RESULTS: This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%-40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.

CONCLUSIONS: The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.}, } @article {pmid35136225, year = {2022}, author = {}, title = {Long COVID and kids: more research is urgently needed.}, journal = {Nature}, volume = {602}, number = {7896}, pages = {183}, doi = {10.1038/d41586-022-00334-w}, pmid = {35136225}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Biomedical Research/*trends ; COVID-19/*complications/epidemiology/immunology/therapy ; COVID-19 Vaccines/administration & dosage/immunology ; Child ; Child, Preschool ; Clinical Trials as Topic/methods ; Cognitive Dysfunction/*epidemiology ; Cohort Studies ; Fatigue/*epidemiology ; Humans ; Prevalence ; *Uncertainty ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35135781, year = {2022}, author = {Iacobucci, G}, title = {Long covid: "Holistic" approach is best, given range of symptoms, say researchers.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o336}, doi = {10.1136/bmj.o336}, pmid = {35135781}, issn = {1756-1833}, } @article {pmid35135496, year = {2022}, author = {Titze-de-Almeida, R and da Cunha, TR and Dos Santos Silva, LD and Ferreira, CS and Silva, CP and Ribeiro, AP and de Castro Moreira Santos Júnior, A and de Paula Brandão, PR and Silva, APB and da Rocha, MCO and Xavier, ME and Titze-de-Almeida, SS and Shimizu, HE and Delgado-Rodrigues, RN}, title = {Persistent, new-onset symptoms and mental health complaints in Long COVID in a Brazilian cohort of non-hospitalized patients.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {133}, pmid = {35135496}, issn = {1471-2334}, support = {TED/MEC n. 9249//Ministério da Educação/ ; }, mesh = {Adult ; Anxiety ; Brazil/epidemiology ; *COVID-19/complications/psychology ; Depression ; Humans ; Memory ; *Mental Health ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections lead to acute- and chronic Long COVID (LC) symptoms. However, few studies have addressed LC sequelae on brain functions. This study was aimed to examine if acute symptoms of coronavirus disease 2019 (COVID-19) would persist during LC, and if memory problems would be correlated with sleep, depressive mood, or anxious complaints.

METHODS: Our work followed a cohort of 236 patients from two public hospitals of the Federal District in mid-western Brazil. Patients' interviews checked for clinical symptoms during acute and LC (5-8 months after real-time reverse transcription polymerase chain reaction, RT-qPCR).

RESULTS: Most cases were non-hospitalized individuals (86.3%) with a median age of 41.2 years. While myalgia (50%), hyposmia (48.3%), and dysgeusia (45.8%) were prevalent symptoms in acute phase, fatigue (21.6%) followed by headache (19.1%) and myalgia (16.1%) commonly occurred during LC. In LC, 39.8% of individuals reported memory complaints, 36.9% felt anxious, 44.9% felt depressed, and 45.8% had sleep problems. Furthermore, memory complaints were associated with sleep problems (adjusted OR 3.206; 95% CI 1.723-6.030) and depressive feelings (adjusted OR 3.981; 95% CI 2.068-7.815).

CONCLUSIONS: The SARS-CoV-2 infection leads to persistent symptoms during LC, in which memory problems may be associated with sleep and depressive complaints.}, } @article {pmid35134812, year = {2022}, author = {Yelin, D and Margalit, I}, title = {Challenges and Management of Long COVID in Individuals with Hematological Illnesses.}, journal = {Acta haematologica}, volume = {145}, number = {3}, pages = {275-281}, pmid = {35134812}, issn = {1421-9662}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has impacted hundreds of millions of people globally, a relatively large proportion of whom continue to suffer from ongoing, sometime debilitating symptoms. This phenomenon, termed "long COVID," is difficult to diagnose and manage because of a paucity of objective findings and despite the abundance of descriptive data published so far. In this review, we aimed to describe the common manifestations of long COVID, diagnostic and management challenges, and address specific aspects in hematologic patients.}, } @article {pmid35133956, year = {2022}, author = {Bonifácio, LP and Csizmar, VNF and Barbosa-Júnior, F and Pereira, APS and Koenigkam-Santos, M and Wada, DT and Gaspar, GG and Carvalho, FS and Bollela, VR and Santana, RC and Souza, JP and Bellissimo-Rodrigues, F}, title = {Long-Term Symptoms among COVID-19 Survivors in Prospective Cohort Study, Brazil.}, journal = {Emerging infectious diseases}, volume = {28}, number = {3}, pages = {730-733}, pmid = {35133956}, issn = {1080-6059}, mesh = {Brazil/epidemiology ; *COVID-19 ; Humans ; Prospective Studies ; SARS-CoV-2 ; Survivors ; }, abstract = {We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.}, } @article {pmid35132606, year = {2022}, author = {Gomes, M and Murray, E and Raftery, J}, title = {Economic Evaluation of Digital Health Interventions: Methodological Issues and Recommendations for Practice.}, journal = {PharmacoEconomics}, volume = {40}, number = {4}, pages = {367-378}, pmid = {35132606}, issn = {1179-2027}, mesh = {*COVID-19/complications ; Cost-Benefit Analysis ; England ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Health care interventions are increasingly being delivered through digital technologies, offering major opportunities for delivering more health gains from scarce health care resources. Digital health interventions (DHIs) raise distinct challenges for economic evaluations compared with drugs and medical devices, not least due to their interacting, evolving features. The implications of the distinctive nature of DHIs for the methodological choices underpinning their economic evaluation is not well understood. This paper provides an in-depth discussion of distinct features of DHIs and how they might impact the design, measurement, analysis and reporting of cost-effectiveness analysis conducted alongside both randomised and non-randomised studies. These include aspects related to choice of comparator, costs and benefits assessment, study perspective and type of economic analysis. We argue that typical methodological standpoints, such as taking a health service perspective, focusing on health-related benefits and adopting cost-utility analyses, as typically adopted in the economic evaluation of non-digital technologies (pharmaceutical drugs and medical devices), are unlikely to be appropriate for DHIs. We illustrate how these methodological aspects can be appropriately addressed in an evaluation of a digitally supported, remote rehabilitation programme for patients with Long Covid in England. We highlight several methodological considerations for improving practice and areas where further methodological work is required.}, } @article {pmid35132414, year = {2022}, author = {Shen, WB and Elahi, M and Logue, J and Yang, P and Baracco, L and Reece, EA and Wang, B and Li, L and Blanchard, TG and Han, Z and Rissman, RA and Frieman, MB and Yang, P}, title = {SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2022.01.31.478476}, pmid = {35132414}, issn = {2692-8205}, support = {P30 AG066530/AG/NIA NIH HHS/United States ; }, abstract = {The neurotropism of SARS-CoV-2 and the phenotypes of infected neurons are still in debate. Long COVID manifests with "brain diseases" and the cause of these brain dysfunction is mysterious. Here, we analyze 34 age- and underlying disease-matched COVID-19 or non-COVID-19 human brains. SARS-CoV-2 RNA, nucleocapsid, and spike proteins are present in neurons of the cognitive centers of all COVID-19 patients, with its non-structural protein NSF2 detected in adult cases but not in the infant case, indicating viral replications in mature neurons. In adult COVID-19 patients without underlying neurodegeneration, SARS-CoV-2 infection triggers Aβ and p-tau deposition, degenerating neurons, microglia activation, and increased cytokine, in some cases with Aβ plaques and p-tau pretangles. The number of SARS-CoV-2 [+] cells is higher in patients with neurodegenerative diseases than in those without such conditions. SARS-CoV-2 further activates microglia and induces Aβ and p-tau deposits in non-Alzheimer's neurodegenerative disease patients. SARS-CoV-2 infects mature neurons derived from inducible pluripotent stem cells from healthy and Alzheimer's disease (AD) individuals through its receptor ACE2 and facilitator neuropilin-1. SARS-CoV-2 triggers AD-like gene programs in healthy neurons and exacerbates AD neuropathology. An AD infectious etiology gene signature is identified through SARS-CoV-2 infection and silencing the top three downregulated genes in human primary neurons recapitulates the neurodegenerative phenotypes of SARS-CoV-2. Thus, our data suggest that SARS-CoV-2 invades the brain and activates an AD-like program.}, } @article {pmid35131989, year = {2022}, author = {Daines, L and Zheng, B and Pfeffer, P and Hurst, JR and Sheikh, A}, title = {A clinical review of long-COVID with a focus on the respiratory system.}, journal = {Current opinion in pulmonary medicine}, volume = {28}, number = {3}, pages = {174-179}, pmid = {35131989}, issn = {1531-6971}, support = {COV/LTE/20/15/CSO_/Chief Scientist Office/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology ; Cough ; Humans ; Respiratory System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system.

RECENT FINDINGS: Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID.

SUMMARY: Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.}, } @article {pmid35131836, year = {2022}, author = {Murray, E and Goodfellow, H and Bindman, J and Blandford, A and Bradbury, K and Chaudhry, T and Fernandez-Reyes, D and Gomes, M and Hamilton, FL and Heightman, M and Henley, W and Hurst, JR and Hylton, H and Linke, S and Pfeffer, P and Ricketts, W and Robson, C and Singh, R and Stevenson, FA and Walker, S and Waywell, J}, title = {Development, deployment and evaluation of digitally enabled, remote, supported rehabilitation for people with long COVID-19 (Living With COVID-19 Recovery): protocol for a mixed-methods study.}, journal = {BMJ open}, volume = {12}, number = {2}, pages = {e057408}, pmid = {35131836}, issn = {2044-6055}, support = {NIHR132243/DH_/Department of Health/United Kingdom ; }, mesh = {Anxiety ; *COVID-19/complications ; Humans ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long COVID-19 is a distressing, disabling and heterogeneous syndrome often causing severe functional impairment. Predominant symptoms include fatigue, cognitive impairment ('brain fog'), breathlessness and anxiety or depression. These symptoms are amenable to rehabilitation delivered by skilled healthcare professionals, but COVID-19 has put severe strain on healthcare systems. This study aims to explore whether digitally enabled, remotely supported rehabilitation for people with long COVID-19 can enable healthcare systems to provide high quality care to large numbers of patients within the available resources. Specific objectives are to (1) develop and refine a digital health intervention (DHI) that supports patient assessment, monitoring and remote rehabilitation; (2) develop implementation models that support sustainable deployment at scale; (3) evaluate the impact of the DHI on recovery trajectories and (4) identify and mitigate health inequalities due to the digital divide.

METHODS AND ANALYSIS: Mixed-methods, theoretically informed, single-arm prospective study, combining methods drawn from engineering/computer science with those from biomedicine. There are four work packages (WP), one for each objective. WP1 focuses on identifying user requirements and iteratively developing the intervention to meet them; WP2 combines qualitative data from users with learning from implementation science and normalisation process theory, to promote adoption, scale-up, spread and sustainability of the intervention; WP3 uses quantitative demographic, clinical and resource use data collected by the DHI to determine illness trajectories and how these are affected by use of the DHI; while WP4 focuses on identifying and mitigating health inequalities and overarches the other three WPs.

ETHICS AND DISSEMINATION: Ethical approval obtained from East Midlands - Derby Research Ethics Committee (reference 288199). Our dissemination strategy targets three audiences: (1) Policy makers, Health service managers and clinicians responsible for delivering long COVID-19 services; (2) patients and the public; (3) academics.

TRIAL REGISTRATION NUMBER: Research Registry number: researchregistry6173.}, } @article {pmid35131031, year = {2022}, author = {Sonnweber, T and Tymoszuk, P and Sahanic, S and Boehm, A and Pizzini, A and Luger, A and Schwabl, C and Nairz, M and Grubwieser, P and Kurz, K and Koppelstätter, S and Aichner, M and Puchner, B and Egger, A and Hoermann, G and Wöll, E and Weiss, G and Widmann, G and Tancevski, I and Löffler-Ragg, J}, title = {Investigating phenotypes of pulmonary COVID-19 recovery: A longitudinal observational prospective multicenter trial.}, journal = {eLife}, volume = {11}, number = {}, pages = {}, pmid = {35131031}, issn = {2050-084X}, support = {GZ 71934//Landes Tirols/ ; IIS 1199-0424//Boehringer Ingelheim/ ; GZ 71934//Land Tirol/ ; }, mesh = {Adult ; Aged ; COVID-19/epidemiology/rehabilitation/*therapy ; Female ; Follow-Up Studies ; Humans ; Intensive Care Units ; Logistic Models ; Longitudinal Studies ; Lung Diseases/diagnosis/*epidemiology/*physiopathology ; Male ; Middle Aged ; Phenotype ; Prospective Studies ; Risk Factors ; SARS-CoV-2 ; Tomography, X-Ray Computed/methods ; }, abstract = {BACKGROUND: The optimal procedures to prevent, identify, monitor, and treat long-term pulmonary sequelae of COVID-19 are elusive. Here, we characterized the kinetics of respiratory and symptom recovery following COVID-19.

METHODS: We conducted a longitudinal, multicenter observational study in ambulatory and hospitalized COVID-19 patients recruited in early 2020 (n = 145). Pulmonary computed tomography (CT) and lung function (LF) readouts, symptom prevalence, and clinical and laboratory parameters were collected during acute COVID-19 and at 60, 100, and 180 days follow-up visits. Recovery kinetics and risk factors were investigated by logistic regression. Classification of clinical features and participants was accomplished by unsupervised and semi-supervised multiparameter clustering and machine learning.

RESULTS: At the 6-month follow-up, 49% of participants reported persistent symptoms. The frequency of structural lung CT abnormalities ranged from 18% in the mild outpatient cases to 76% in the intensive care unit (ICU) convalescents. Prevalence of impaired LF ranged from 14% in the mild outpatient cases to 50% in the ICU survivors. Incomplete radiological lung recovery was associated with increased anti-S1/S2 antibody titer, IL-6, and CRP levels at the early follow-up. We demonstrated that the risk of perturbed pulmonary recovery could be robustly estimated at early follow-up by clustering and machine learning classifiers employing solely non-CT and non-LF parameters.

CONCLUSIONS: The severity of acute COVID-19 and protracted systemic inflammation is strongly linked to persistent structural and functional lung abnormality. Automated screening of multiparameter health record data may assist in the prediction of incomplete pulmonary recovery and optimize COVID-19 follow-up management.

FUNDING: The State of Tyrol (GZ 71934), Boehringer Ingelheim/Investigator initiated study (IIS 1199-0424).

CLINICAL TRIAL NUMBER: ClinicalTrials.gov: NCT04416100.}, } @article {pmid35130818, year = {2022}, author = {Whiteside, DM and Basso, MR and Naini, SM and Porter, J and Holker, E and Waldron, EJ and Melnik, TE and Niskanen, N and Taylor, SE}, title = {Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning.}, journal = {The Clinical neuropsychologist}, volume = {36}, number = {4}, pages = {806-828}, doi = {10.1080/13854046.2022.2030412}, pmid = {35130818}, issn = {1744-4144}, support = {UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Cognition ; *Cognition Disorders/diagnosis/etiology ; Disease Progression ; Executive Function ; Female ; Humans ; Neuropsychological Tests ; }, abstract = {OBJECTIVE: Long-term cognitive sequelae of COVID-19 have not been extensively studied. This study provides initial results on cognitive outcomes in Post-Acute Sequelae of COVID-19 (PASC).Participants and Methods: This study examined 53 consecutive outpatients diagnosed with COVID-19. Four participants were excluded due to performance validity test failure. All participants had positive COVID-19 tests, reported cognitive concerns, and completed neuropsychological tests to assess performance validity, attention/working memory, processing speed, memory, language, visual-spatial, executive functioning, motor, and emotional functioning. The sample was mostly white (89.8%), female (83.7%), and never hospitalized (69.4%) for COVID-19.

RESULTS: Analyses indicated no mean scores in the Impaired range (>2 standard deviations [SD] below normative mean) on objective cognitive testing and a low base rate of Impaired test scores. Higher (>20%) base rates of Borderline performance (1-2 SDs below normative mean) were found on some measures. There was also evidence for frequently elevated mean scores on mood measures which correlated with some cognitive measures and the number of Borderline scores per participants.

CONCLUSIONS: The results were noteworthy for infrequent Impaired scores, and significant correlations between cognition and mood/anxiety measures, but not between cognitive performance and premorbid vascular risk factors, psychiatric diagnoses, or COVID-19 disease severity. Results suggest that psychological distress was prominent in PASC and related to objective cognitive performance, but objective cognitive performance was unrelated to cognitive complaints. Other contributing factors may include fatigue/sleep issues. Neurologically based cognitive deficits were not suggested by the results.}, } @article {pmid35129713, year = {2022}, author = {Miglis, MG and Larsen, N and Muppidi, S}, title = {Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {32}, number = {2}, pages = {91-94}, pmid = {35129713}, issn = {1619-1560}, mesh = {Autonomic Nervous System ; *COVID-19/complications ; Humans ; *Tachycardia, Sinus/diagnosis ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35129097, year = {2022}, author = {Hegde, S and Sreeram, S and Bhat, KR and Satish, V and Shekar, S and Babu, M}, title = {Evaluation of post-COVID health status using the EuroQol-5D-5L scale.}, journal = {Pathogens and global health}, volume = {116}, number = {8}, pages = {498-508}, pmid = {35129097}, issn = {2047-7732}, mesh = {Humans ; Infant, Newborn ; *Quality of Life ; Aftercare ; SARS-CoV-2 ; *COVID-19/epidemiology ; Patient Discharge ; Health Status ; Surveys and Questionnaires ; }, abstract = {SARS-CoV-2 has had a lasting effect on the overall health of recovered patients, called 'long COVID'. Currently, there is a lack of a validated standard questionnaire to assess post-COVID health status. A retrospective observational study involving the recovered COVID patients admitted to a secondary care hospital in India between June to December 2020 (n = 123), was conducted using the EuroQol-5D-5L scale at discharge, 4 weeks and 8 weeks post-discharge. A significant difference in anxiety/depression scores was found (χ[2] = 65.6, p < 0.000) among the 3 categories of time (discharge, 4 weeks and 8 weeks). The anxiety/depression dimension scores showed a significant change (p < 0.0001) between discharge and 8 weeks, using paired t-test. Age had a significant relationship with the anxiety/depression dimension at 4 weeks (OR = 5.617, 95% CI = 1.0320-30.5746, p < 0.05). A significant difference was found using Kruskal-Wallis rank-sum test on mean index scores (χ[2] = 60.0, p < 0.000) among the three categories of time (discharge, 4 weeks and 8 weeks). There was a statistically significant difference of time on EQ Index scores as determined by one-way repeated measures ANOVA (F(2,375) = 18.941, p = <0.00001). Our study found time to have a statistically significant impact on the mean index scores, level sum scores and dimension scores. Smoking was found to be significantly associated with usual activity scores at 4 weeks. The most remarkable changes occurred in the anxiety/depression dimension. Overall, there was a general trend of health improvement.}, } @article {pmid35128398, year = {2022}, author = {Zhao, S and Shibata, K and Hellyer, PJ and Trender, W and Manohar, S and Hampshire, A and Husain, M}, title = {Rapid vigilance and episodic memory decrements in COVID-19 survivors.}, journal = {Brain communications}, volume = {4}, number = {1}, pages = {fcab295}, pmid = {35128398}, issn = {2632-1297}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/V036858/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Recent studies indicate that COVID-19 infection can lead to serious neurological consequences in a small percentage of individuals. However, in the months following acute illness, many more suffer from fatigue, low motivation, disturbed mood, poor sleep and cognitive symptoms, colloquially referred to as 'brain fog'. But what about individuals who had asymptomatic to moderate COVID-19 and reported no concerns after recovering from COVID-19? Here, we examined a wide range of cognitive functions critical for daily life (including sustained attention, memory, motor control, planning, semantic reasoning, mental rotation and spatial-visual attention) in people who had previously suffered from COVID-19 but were not significantly different from a control group on self-reported fatigue, forgetfulness, sleep abnormality, motivation, depression, anxiety and personality profile. Reassuringly, COVID-19 survivors performed well in most abilities tested, including working memory, executive function, planning and mental rotation. However, they displayed significantly worse episodic memory (up to 6 months post-infection) and greater decline in vigilance with time on task (for up to 9 months). Overall, the results show that specific chronic cognitive changes following COVID-19 are evident on objective testing even amongst those who do not report a greater symptom burden. Importantly, in the sample tested here, these were not significantly different from normal after 6-9 months, demonstrating evidence of recovery over time.}, } @article {pmid35127274, year = {2022}, author = {Thallapureddy, K and Thallapureddy, K and Zerda, E and Suresh, N and Kamat, D and Rajasekaran, K and Moreira, A}, title = {Long-Term Complications of COVID-19 Infection in Adolescents and Children.}, journal = {Current pediatrics reports}, volume = {10}, number = {1}, pages = {11-17}, pmid = {35127274}, issn = {2167-4841}, abstract = {PURPOSE OF REVIEW: Compared to adults, post-COVID-19 symptoms are uncommon and have not been thoroughly evaluated in children. This review summarizes the literature in terms of persistent symptoms in children and adolescents after SARS-CoV-2 infection.

RECENT FINDINGS: Children were less likely to develop long COVID when compared to adults. Older children (e.g., adolescents) and those who had symptomatic COVID-19 had a higher probability for long COVID.

SUMMARY: Families and health care providers need to be aware of a new constellation of long COVID symptoms in the pediatric population. More evidence and time are needed to better understand the potential effects of long COVID-19 in children and adolescents. In comparison to adults, children are less likely to have persistent COVID-19 symptoms.}, } @article {pmid35125594, year = {2022}, author = {Hamzelou, J}, title = {What covid-19 does to the brain.}, journal = {New scientist (1971)}, volume = {253}, number = {3371}, pages = {19}, doi = {10.1016/S0262-4079(22)00130-0}, pmid = {35125594}, issn = {0262-4079}, abstract = {The latest evidence suggests neurological symptoms of long covid, such as brain fog, are caused by an immune reaction - and should be reversible, reports Jessica Hamzelou.}, } @article {pmid35124546, year = {2022}, author = {Azevedo, MN and Rodrigues, EDS and Passos, EAFV and Filho, MAB and Barreto, APA and Lima, MCC and Barreto, ML and Castro-de-Araujo, LFS}, title = {Multimorbidity associated with anxiety symptomatology in post-COVID patients.}, journal = {Psychiatry research}, volume = {309}, number = {}, pages = {114427}, pmid = {35124546}, issn = {1872-7123}, support = {MC_PC_MR/T03355X/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Anxiety/diagnosis/epidemiology ; *COVID-19 ; Depression/diagnosis ; Humans ; Male ; Multimorbidity ; *Pandemics ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic hit individuals with chronic conditions the hardest. It is known that anxiety symptoms are frequent in post-COVID conditions. We want to examine whether multimorbidity is associated with anxiety in post-COVID patients. We reported descriptive statistics from 389 post-COVID patients and perform a linear regression with anxiety symptoms measured using the Hospital Anxiety and Depression (HAD) scale. For each extra chronic condition, there was a mean increase of 0.11 in the HAD-anxiety score. However, there was a reduction for age and being male. These findings can potentially help policy-makers better organize post-COVID health services and improve patients care.}, } @article {pmid35121715, year = {2022}, author = {Siberry, VGR and Rowe, PC}, title = {Pediatric Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Overlaps and Opportunities.}, journal = {The Pediatric infectious disease journal}, volume = {41}, number = {4}, pages = {e139-e141}, pmid = {35121715}, issn = {1532-0987}, mesh = {*COVID-19/complications ; Child ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35121209, year = {2022}, author = {Premraj, L and Kannapadi, NV and Briggs, J and Seal, SM and Battaglini, D and Fanning, J and Suen, J and Robba, C and Fraser, J and Cho, SM}, title = {Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis.}, journal = {Journal of the neurological sciences}, volume = {434}, number = {}, pages = {120162}, pmid = {35121209}, issn = {1878-5883}, support = {K23 HL157610/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Anxiety/epidemiology/etiology/psychology ; *COVID-19/complications/epidemiology ; Fatigue/diagnosis ; Headache/epidemiology ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis.

OBJECTIVE: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.

DATA SOURCES: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.

STUDY SELECTION: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.

DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.

The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.

RESULTS: Of 1458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were: fatigue (37%, 95% CI: 24%-50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%-34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced frequency of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR: 1.9, 95% CI: 1.4-2.3). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.

CONCLUSIONS AND RELEVANCE: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.}, } @article {pmid35118594, year = {2022}, author = {Borel, M and Xie, L and Kapera, O and Mihalcea, A and Kahn, J and Messiah, SE}, title = {Long-term physical, mental and social health effects of COVID-19 in the pediatric population: a scoping review.}, journal = {World journal of pediatrics : WJP}, volume = {18}, number = {3}, pages = {149-159}, pmid = {35118594}, issn = {1867-0687}, mesh = {Adolescent ; Adult ; *COVID-19 ; Child ; Fatigue/diagnosis/epidemiology/etiology ; Humans ; Pandemics ; Physical Examination ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The majority of coronavirus disease 2019 (COVID-19) symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection, which raises questions about the long-term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic.

METHODS: A search was conducted using PubMed, Web of Science, Science Direct, and Cochrane between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) severe acute respiratory syndrome coronavirus 2 in children; (3) English language; and (4) human studies only.

RESULTS: The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. In addition, COVID-19 has had a moderate impact on children and adolescents' social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes.

CONCLUSIONS: There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes.}, } @article {pmid35116025, year = {2021}, author = {Plüß, M and Mese, K and Kowallick, JT and Schuster, A and Tampe, D and Tampe, B}, title = {Case Report: Cytomegalovirus Reactivation and Pericarditis Following ChAdOx1 nCoV-19 Vaccination Against SARS-CoV-2.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {784145}, pmid = {35116025}, issn = {1664-3224}, mesh = {Aged ; Antiviral Agents/therapeutic use ; COVID-19/prevention & control ; ChAdOx1 nCoV-19/*adverse effects ; Cytomegalovirus/*drug effects/physiology ; Cytomegalovirus Infections/chemically induced/drug therapy/virology ; Female ; Humans ; Pericarditis/*chemically induced/drug therapy/virology ; SARS-CoV-2/*immunology ; Treatment Outcome ; Valganciclovir/therapeutic use ; Viremia/chemically induced/drug therapy/virology ; Virus Activation/*drug effects ; }, abstract = {As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.}, } @article {pmid35114994, year = {2022}, author = {Munblit, D and Nicholson, TR and Needham, DM and Seylanova, N and Parr, C and Chen, J and Kokorina, A and Sigfrid, L and Buonsenso, D and Bhatnagar, S and Thiruvengadam, R and Parker, AM and Preller, J and Avdeev, S and Klok, FA and Tong, A and Diaz, JV and Groote, W and Schiess, N and Akrami, A and Simpson, F and Olliaro, P and Apfelbacher, C and Rosa, RG and Chevinsky, JR and Saydah, S and Schmitt, J and Guekht, A and Gorst, SL and Genuneit, J and Reyes, LF and Asmanov, A and O'Hara, ME and Scott, JT and Michelen, M and Stavropoulou, C and Warner, JO and Herridge, M and Williamson, PR}, title = {Studying the post-COVID-19 condition: research challenges, strategies, and importance of Core Outcome Set development.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {50}, pmid = {35114994}, issn = {1741-7015}, support = {001/WHO_/World Health Organization/International ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; *COVID-19/complications ; Child ; Disease Progression ; Humans ; Outcome Assessment, Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: A substantial portion of people with COVID-19 subsequently experience lasting symptoms including fatigue, shortness of breath, and neurological complaints such as cognitive dysfunction many months after acute infection. Emerging evidence suggests that this condition, commonly referred to as long COVID but also known as post-acute sequelae of SARS-CoV-2 infection (PASC) or post-COVID-19 condition, could become a significant global health burden.

MAIN TEXT: While the number of studies investigating the post-COVID-19 condition is increasing, there is no agreement on how this new disease should be defined and diagnosed in clinical practice and what relevant outcomes to measure. There is an urgent need to optimise and standardise outcome measures for this important patient group both for clinical services and for research and to allow comparing and pooling of data.

CONCLUSIONS: A Core Outcome Set for post-COVID-19 condition should be developed in the shortest time frame possible, for improvement in data quality, harmonisation, and comparability between different geographical locations. We call for a global initiative, involving all relevant partners, including, but not limited to, healthcare professionals, researchers, methodologists, patients, and caregivers. We urge coordinated actions aiming to develop a Core Outcome Set (COS) for post-COVID-19 condition in both the adult and paediatric populations.}, } @article {pmid35114535, year = {2022}, author = {Cau, R and Faa, G and Nardi, V and Balestrieri, A and Puig, J and Suri, JS and SanFilippo, R and Saba, L}, title = {Long-COVID diagnosis: From diagnostic to advanced AI-driven models.}, journal = {European journal of radiology}, volume = {148}, number = {}, pages = {110164}, pmid = {35114535}, issn = {1872-7727}, mesh = {Artificial Intelligence ; *COVID-19/complications ; Humans ; RNA, Viral ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-COV 2 is recognized to be responsible for a multi-organ syndrome. In most patients, symptoms are mild. However, in certain subjects, COVID-19 tends to progress more severely. Most of the patients infected with SARS-COV2 fully recovered within some weeks. In a considerable number of patients, like many other viral infections, various long-lasting symptoms have been described, now defined as "long COVID-19 syndrome". Given the high number of contagious over the world, it is necessary to understand and comprehend this emerging pathology to enable early diagnosis and improve patents outcomes. In this scenario, AI-based models can be applied in long-COVID-19 patients to assist clinicians and at the same time, to reduce the considerable impact on the care and rehabilitation unit. The purpose of this manuscript is to review different aspects of long-COVID-19 syndrome from clinical presentation to diagnosis, highlighting the considerable impact that AI can have.}, } @article {pmid35114136, year = {2022}, author = {Bechmann, N and Barthel, A and Schedl, A and Herzig, S and Varga, Z and Gebhard, C and Mayr, M and Hantel, C and Beuschlein, F and Wolfrum, C and Perakakis, N and Poston, L and Andoniadou, CL and Siow, R and Gainetdinov, RR and Dotan, A and Shoenfeld, Y and Mingrone, G and Bornstein, SR}, title = {Sexual dimorphism in COVID-19: potential clinical and public health implications.}, journal = {The lancet. Diabetes & endocrinology}, volume = {10}, number = {3}, pages = {221-230}, pmid = {35114136}, issn = {2213-8595}, support = {CH/16/3/32406/BHF_/British Heart Foundation/United Kingdom ; RG/16/14/32397/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/epidemiology/physiopathology ; Female ; *Health Status Disparities ; Humans ; Hypothalamo-Hypophyseal System ; Male ; Pituitary-Adrenal System ; Public Health ; *Sex Characteristics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.}, } @article {pmid35113831, year = {2022}, author = {Malizos, KN}, title = {Long COVID-19: A New Challenge to Public Health.}, journal = {The Journal of bone and joint surgery. American volume}, volume = {104}, number = {3}, pages = {205-206}, doi = {10.2106/JBJS.21.01276}, pmid = {35113831}, issn = {1535-1386}, mesh = {COVID-19/*complications ; Humans ; *Public Health ; }, } @article {pmid35112786, year = {2022}, author = {Reiken, S and Sittenfeld, L and Dridi, H and Liu, Y and Liu, X and Marks, AR}, title = {Alzheimer's-like signaling in brains of COVID-19 patients.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {18}, number = {5}, pages = {955-965}, pmid = {35112786}, issn = {1552-5279}, mesh = {*Alzheimer Disease/genetics ; Brain/pathology ; *COVID-19/complications ; Calcium Signaling/physiology ; Humans ; Ryanodine Receptor Calcium Release Channel/genetics/metabolism ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.

METHODS: Brain lysates from control and COVID-19 patients were analyzed for oxidative stress and inflammatory signaling pathway markers, and measurements of Alzheimer's disease (AD)-linked signaling biochemistry. Post-translational modifications of the ryanodine receptor/calcium (Ca2[+]) release channels (RyR) on the endoplasmic reticuli (ER), known to be linked to AD, were also measured by co-immunoprecipitation/immunoblotting of the brain lysates.

RESULTS: We provide evidence linking SARS-CoV-2 infection to activation of TGF-β signaling and oxidative overload. The neuropathological pathways causing tau hyperphosphorylation typically associated with AD were also shown to be activated in COVID-19 patients. RyR2 in COVID-19 brains demonstrated a "leaky" phenotype, which can promote cognitive and behavioral defects.

DISCUSSION: COVID-19 neuropathology includes AD-like features and leaky RyR2 channels could be a therapeutic target for amelioration of some cognitive defects associated with SARS-CoV-2 infection and long COVID.}, } @article {pmid35111870, year = {2022}, author = {Ram-Mohan, N and Kim, D and Rogers, AJ and Blish, CA and Nadeau, KC and Blomkalns, AL and Yang, S}, title = {Association Between SARS-CoV-2 RNAemia and Postacute Sequelae of COVID-19.}, journal = {Open forum infectious diseases}, volume = {9}, number = {2}, pages = {ofab646}, pmid = {35111870}, issn = {2328-8957}, support = {R01 AI137272/AI/NIAID NIH HHS/United States ; R01 AI153133/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; }, abstract = {Determinants of Post-Acute Sequelae of COVID-19 are not known. Here we show that 83.3% of patients with viral RNA in blood (RNAemia) at presentation were symptomatic in the post-acute phase. RNAemia at presentation successfully predicted PASC, independent of patient demographics, worst disease severity, and length of symptoms.}, } @article {pmid35108477, year = {2022}, author = {Rubin, EJ and Baden, LR and Rosen, CJ and Morrissey, S}, title = {Audio Interview: Studying Long Covid.}, journal = {The New England journal of medicine}, volume = {386}, number = {5}, pages = {e20}, doi = {10.1056/NEJMe2201619}, pmid = {35108477}, issn = {1533-4406}, mesh = {Adult ; COVID-19/*complications/epidemiology/psychology ; Case-Control Studies ; Child ; Humans ; Immunity, Herd ; Patient Acuity ; *Patient Selection ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35106317, year = {2022}, author = {Peluso, MJ and Kelly, JD and Lu, S and Goldberg, SA and Davidson, MC and Mathur, S and Durstenfeld, MS and Spinelli, MA and Hoh, R and Tai, V and Fehrman, EA and Torres, L and Hernandez, Y and Williams, MC and Arreguin, MI and Ngo, LH and Deswal, M and Munter, SE and Martinez, EO and Anglin, KA and Romero, MD and Tavs, J and Rugart, PR and Chen, JY and Sans, HM and Murray, VW and Ellis, PK and Donohue, KC and Massachi, JA and Weiss, JO and Mehdi, I and Pineda-Ramirez, J and Tang, AF and Wenger, MA and Assenzio, MT and Yuan, Y and Krone, MR and Rutishauser, RL and Rodriguez-Barraquer, I and Greenhouse, B and Sauceda, JA and Gandhi, M and Scheffler, AW and Hsue, PY and Henrich, TJ and Deeks, SG and Martin, JN}, title = {Persistence, Magnitude, and Patterns of Postacute Symptoms and Quality of Life Following Onset of SARS-CoV-2 Infection: Cohort Description and Approaches for Measurement.}, journal = {Open forum infectious diseases}, volume = {9}, number = {2}, pages = {ofab640}, pmid = {35106317}, issn = {2328-8957}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; K23 AI076614/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; T32 HL007731/HL/NHLBI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: There is mounting evidence for the presence of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life.

METHODS: We assembled a cohort of adults with a documented history of SARS-CoV-2 RNA positivity at ≥2 weeks past onset of coronavirus disease 2019 (COVID-19) symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life.

RESULTS: Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 were symptomatic but not hospitalized, and 44 were symptomatic and hospitalized. During the postacute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping, and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared with pre-COVID-19. Two clusters of symptom domains were identified.

CONCLUSIONS: Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple subphenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various subgroups of PASC.}, } @article {pmid35105498, year = {2022}, author = {Hsu, WL and Chang, YW and Horng, YS and Hsu, YT and Wu, PS}, title = {The successful rehabilitation of a 75-year-old female with debilitating long COVID: A case report.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {121}, number = {7}, pages = {1342-1347}, pmid = {35105498}, issn = {0929-6646}, mesh = {Activities of Daily Living ; Aged ; *COVID-19/complications ; *Coronavirus ; *Coronavirus Infections/complications/therapy ; Female ; Humans ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {A 75-year-old previously healthy female became severely ill, functionally dependent, and required long-term home oxygen therapy, after recovery from coronavirus disease 2019 (COVID-19) with acute respiratory failure and extensive pulmonary fibrosis. After two months of respiratory muscle training and a comprehensive cardiopulmonary rehabilitation program, her dyspnea, physical performance, pulmonary function parameters, and activities of daily living rapidly improved. This Case highlights the importance of a timely active rehabilitation program for COVID-19 survivors experiencing the long-term effects of coronavirus (long COVID).}, } @article {pmid35103573, year = {2022}, author = {Butler, SJ and Santhosh, L and Gupta, S and Parker, AM and Gershon, AS}, title = {Long COVID Patient Fact Sheet.}, journal = {American journal of respiratory and critical care medicine}, volume = {205}, number = {3}, pages = {P5-P6}, doi = {10.1164/rccm.2053P5}, pmid = {35103573}, issn = {1535-4970}, mesh = {COVID-19/*complications/diagnosis/etiology/therapy ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35103255, year = {2022}, author = {Samara, A and Herlenius, E and O' Brien, P and Khalil, A}, title = {Potential role of neurofilament in COVID-19 and preeclampsia.}, journal = {Cell reports. Medicine}, volume = {3}, number = {1}, pages = {100490}, pmid = {35103255}, issn = {2666-3791}, mesh = {Biomarkers/blood ; COVID-19/*blood/*epidemiology/virology ; Comorbidity ; Female ; Humans ; Incidence ; Neurofilament Proteins/*blood ; Pre-Eclampsia/*blood/*epidemiology ; Pregnancy ; *SARS-CoV-2 ; }, abstract = {Neurofilament light (NFL) is a promising circulating biomarker in preeclampsia and COVID-19, even without evident neurological complications. Several pathways might contribute to the elevated serum NFL levels seen in both pathologies. Future studies will determine whether NFL is a long COVID marker and delineate NFL's role in COVID-19-associated preeclampsia.}, } @article {pmid35101537, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Rodríguez-Jiménez, J and Navarro-Pardo, E and Pellicer-Valero, OJ}, title = {Exploring the recovery curves for long-term post-COVID functional limitations on daily living activities: The LONG-COVID-EXP-CM multicenter study.}, journal = {The Journal of infection}, volume = {84}, number = {5}, pages = {722-746}, pmid = {35101537}, issn = {1532-2742}, mesh = {*COVID-19/complications ; Hospitalization ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35098861, year = {2022}, author = {Whiteside, DM and Naini, SM and Basso, MR and Waldron, EJ and Holker, E and Porter, J and Niskanen, N and Melnik, TE and Taylor, SE}, title = {Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection part 2: Psychological functioning.}, journal = {The Clinical neuropsychologist}, volume = {36}, number = {4}, pages = {829-847}, doi = {10.1080/13854046.2022.2030411}, pmid = {35098861}, issn = {1744-4144}, support = {UL1 TR002494/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Disease Progression ; Female ; Humans ; Male ; Neuropsychological Tests ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Limited research investigating the long-term psychological and emotional correlates of COVID-19 infection has been completed. The current study begins to address this limitation in patients experiencing Post-Acute Sequelae SARS-CoV-2 (PASC; e.g. "Long COVID"). Participants were 43 consecutive neuropsychological outpatients diagnosed with PASC and who completed the Personality Assessment Inventory (PAI). The sample was predominantly female (n = 36) and white (n = 32). Effect sizes compared to the normative mean T scores and base rates of elevated (T > 69) scores were calculated. PAI scales measuring somatic preoccupation and depression had large effect sizes and the highest base rates of scale elevations, with the mean T score at approximately the normative cutoff for clinical significance (T = 70). The Schizophrenia Thought Disorder subscale (SCZ-T) also had a large effect size and high base rate of elevation, likely reflecting cognitive concerns. Scales measuring anxiety had medium effect sizes. The other PAI scales generally had small to negligible effect sizes. There were no significant differences between hospitalized and non-hospitalized participants on the PAI. Overall, PAI scales measuring psychological distress, particularly somatic preoccupation and depression, were the most frequently elevated in the participants. The specific reasons for somatic preoccupation could not be determined in this study. Potential explanations include a vulnerability to distress in Long COVID patients, premorbid somatic preoccupation perhaps motivating these patients to seek clinical attention, or socioenvironmental factors leading some COVID patients to be somatically preoccupied with minor physiological changes and attribute those changes to COVID-19.}, } @article {pmid35096923, year = {2021}, author = {Santinelli, L and Laghi, L and Innocenti, GP and Pinacchio, C and Vassalini, P and Celani, L and Lazzaro, A and Borrazzo, C and Marazzato, M and Tarsitani, L and Koukopoulos, AE and Mastroianni, CM and d'Ettorre, G and Ceccarelli, G}, title = {Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {756177}, pmid = {35096923}, issn = {2296-861X}, abstract = {Long COVID refers to patients with symptoms as fatigue, "brain fog," pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.}, } @article {pmid35096282, year = {2022}, author = {Greene, T and El-Leithy, S and Billings, J and Albert, I and Birch, J and Campbell, M and Ehntholt, K and Fortune, L and Gilbert, N and Grey, N and Hana, L and Kennerley, H and Lee, D and Lunn, S and Murphy, D and Robertson, M and Wade, D and Brewin, CR and Bloomfield, MAP}, title = {Anticipating PTSD in severe COVID survivors: the case for screen-and-treat.}, journal = {European journal of psychotraumatology}, volume = {13}, number = {1}, pages = {1959707}, pmid = {35096282}, issn = {2000-8066}, mesh = {COVID-19/epidemiology/*psychology ; Humans ; Mass Screening ; Pandemics ; Stress Disorders, Post-Traumatic/diagnosis/*epidemiology/psychology ; Survivors/*psychology ; }, abstract = {Based on research from previous pandemics, studies of critical care survivors, and emerging COVID-19 data, we estimate that up to 30% of survivors of severe COVID will develop PTSD. PTSD is frequently undetected across primary and secondary care settings and the psychological needs of survivors may be overshadowed by a focus on physical recovery. Delayed PTSD diagnosis is associated with poor outcomes. There is a clear case for survivors of severe COVID to be systematically screened for PTSD, and those that develop PTSD should receive timely access to evidence-based treatment for PTSD and other mental health problems by multidisciplinary teams.}, } @article {pmid35095170, year = {2022}, author = {Ambrosino, N}, title = {Long COVID: Impact and Comprehensive Management. A Never Ending Story?.}, journal = {Archivos de bronconeumologia}, volume = {58}, number = {6}, pages = {469-470}, pmid = {35095170}, issn = {1579-2129}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35095003, year = {2022}, author = {Zalat, M and Bolbol, S}, title = {Telework benefits and associated health problems during the long COVID-19 era.}, journal = {Work (Reading, Mass.)}, volume = {71}, number = {2}, pages = {371-378}, doi = {10.3233/WOR-210691}, pmid = {35095003}, issn = {1875-9270}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Female ; Humans ; Male ; SARS-CoV-2 ; *Teleworking ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Teleworking became a necessary practice as an alternative to office work during the long COVID-19 era.

OBJECTIVES: To recognize the telework associated benefits and health problems and to assess the relationship between some teleworkers' characteristics, their health problems with job satisfaction and recuperation for promoting telework practices.

METHODS: A cross-sectional online survey was conducted among employees working remotely in different work sectors using a questionnaire assessing job satisfaction and recuperation.

RESULTS: Telework benefits included saving time and money (89.3%), minimizing the COVID-19 spread (86.9%), and balancing of work and life (63.4%). Telework associated health problems included musculoskeletal (78.2%), work-related stress (65.9%), and visual problems (47%). Telework job satisfaction was significantly higher among married male workers, working less than 40hs/week, and with previous remote working experience before COVID-19. On the other hand, married female teleworkers working more than 40hs/week and without previous remote working experience before COVID-19 had significantly more perceived fatigue and less recuperation. All teleworkers with reported health problems showed significantly more perceived fatigue and less recuperation.

CONCLUSIONS: More than half of the participants recommended continuing teleworking post-COVID-19 due to its benefits on their working and social life. Telework would enables the employers to adapt and satisfy the teleworkers' expectations to maintain their work and productivity.}, } @article {pmid35091474, year = {2022}, author = {Wise, J}, title = {Covid-19: Antibody "signature" could predict risk of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o245}, doi = {10.1136/bmj.o245}, pmid = {35091474}, issn = {1756-1833}, } @article {pmid35091425, year = {2022}, author = {Sivan, M and Wright, S and Hughes, S and Calvert, M}, title = {Using condition specific patient reported outcome measures for long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o257}, doi = {10.1136/bmj.o257}, pmid = {35091425}, issn = {1756-1833}, mesh = {COVID-19/*complications ; Humans ; Outcome Assessment, Health Care/methods ; *Patient Reported Outcome Measures ; SARS-CoV-2 ; *Syndrome ; }, } @article {pmid35091414, year = {2022}, author = {Hutchinson, J and Checkland, K and Munford, L and Khavandi, S and Sutton, M}, title = {Long COVID in general practice: an analysis of the equity of NHS England's enhanced service specification.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {715}, pages = {85-86}, pmid = {35091414}, issn = {1478-5242}, mesh = {*COVID-19/complications/epidemiology ; England/epidemiology ; *General Practice ; Humans ; SARS-CoV-2 ; State Medicine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35091402, year = {2022}, author = {Spiers, N}, title = {Recognising and bearing the burden of long COVID-related disability.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {715}, pages = {70}, pmid = {35091402}, issn = {1478-5242}, mesh = {*COVID-19/complications/epidemiology ; *Disabled Persons ; Humans ; Quality-Adjusted Life Years ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35090015, year = {2022}, author = {Strahm, C and Seneghini, M and Güsewell, S and Egger, T and Leal-Neto, O and Brucher, A and Lemmenmeier, E and Meier Kleeb, D and Möller, JC and Rieder, P and Ruetti, M and Rutz, R and Schmid, HR and Stocker, R and Vuichard-Gysin, D and Wiggli, B and Besold, U and Kuster, SP and McGeer, A and Risch, L and Friedl, A and Schlegel, M and Schmid, D and Vernazza, P and Kahlert, CR and Kohler, P}, title = {Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Results of a Prospective Multicenter Cohort.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {1}, pages = {e1011-e1019}, pmid = {35090015}, issn = {1537-6591}, mesh = {Asymptomatic Infections/epidemiology ; *COVID-19/complications/epidemiology ; Fatigue ; Female ; Health Personnel ; Humans ; Male ; *Olfaction Disorders ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed.

METHODS: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

RESULTS: Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

CONCLUSIONS: Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.}, } @article {pmid35088048, year = {2021}, author = {Longobardi, I and do Prado, DML and Goessler, KF and de Oliveira Júnior, GN and de Andrade, DCO and Gualano, B and Roschel, H}, title = {Benefits of Home-Based Exercise Training Following Critical SARS-CoV-2 Infection: A Case Report.}, journal = {Frontiers in sports and active living}, volume = {3}, number = {}, pages = {791703}, pmid = {35088048}, issn = {2624-9367}, abstract = {In the current scenario, in which an elevated number of COVID-19 survivors present with severe physical deconditioning, exercise intolerance, persistent symptoms, and other post-acute consequences, effective rehabilitation strategies are of utmost relevance. In this study, we report for the first time the effect of home-based exercise training (HBET) in a survivor patient from critical COVID-19 illness. A 67-year-old woman who had critical COVID-19 disease [71 days of hospitalization, of which 49 days were in the intensive care unit (ICU) with invasive mechanical ventilation due to respiratory failure] underwent a 10-week HBET aiming to recovering overall physical condition. Before and after the intervention, we assessed cardiopulmonary parameters, skeletal muscle strength and functionality, fatigue severity, and self-reported persistent symptoms. At baseline (3 months after discharge), she presented with severe impairment in cardiorespiratory functional capacity (<50% age predicted VO2peak). After the intervention, remarkable improvements in VO2peak (from 10.61 to 15.48 mL·kg[-1]·min[-1], Δ: 45.9%), oxygen uptake efficiency slope (OUES; from 1.0 to 1.3 L·min[-1], Δ: 30.1%), HR/VO2 slope (from 92 to 52 bpm·L[-1], Δ: -43.5%), the lowest VE/VCO2 ratio (from 35.4 to 32.9 L·min[-1], Δ: -7.1%), and exertional dyspnea were observed. In addition, handgrip strength (from 22 to 27 kg, Δ: 22.7%), 30-s Sit-to-Stand (30-STS; from 14 to 16 repetitions, Δ:14.3%), Timed-Up-and-Go (TUG; from 8.25 to 7.01 s, Δ: -15%) performance and post-COVID functional status (PCFS) score (from 4 to 2) were also improved from baseline to post-intervention. Self-reported persistent symptoms were also improved, and Fatigue Severity Scale (FSS) score decreased (from 4 to 2.7) from baseline to post-intervention. This is the first evidence that a semi-supervised, HBET program may be safe and potentially effective in improving cardiorespiratory and physical functionality in COVID-19 survivors. Controlled studies are warranted to confirm these findings.}, } @article {pmid35087250, year = {2022}, author = {Conlon, AM}, title = {Daily briefing: Vaccination could reduce long COVID risk.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-022-00201-8}, pmid = {35087250}, issn = {1476-4687}, } @article {pmid35086863, year = {2022}, author = {Jreidini, C}, title = {How can you help me integrate my long covid care?.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {n3102}, doi = {10.1136/bmj.n3102}, pmid = {35086863}, issn = {1756-1833}, mesh = {COVID-19/*complications/diagnosis/therapy/virology ; Humans ; Patient Education as Topic ; Patient Participation ; SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35086782, year = {2022}, author = {Martín-Garrido, I and Medrano-Ortega, FJ}, title = {Beyond acute SARS-CoV-2 infection: A new challenge for Internal Medicine.}, journal = {Revista clinica espanola}, volume = {222}, number = {3}, pages = {176-179}, pmid = {35086782}, issn = {2254-8874}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, abstract = {Infection with the new SARS-CoV-2 coronavirus has reached pandemic proportions, with a very high death toll worldwide. Despite the scientific community's strenuous efforts to address this disease in its acute phase, as well as in prevention through the development of vaccines in record time, there remains another important workhorse: understanding and treating the persistence of symptoms beyond the acute phase, the so-called protracted COVID-19 syndrome or persistent COVID. These persistent manifestations affect several organs and systems and may depend on both the pathogenic mechanisms of the virus and the pathophysiological response of the patient. One year after the onset of this pandemic, there is an urgent need to address this situation from a comprehensive approach.}, } @article {pmid35086489, year = {2022}, author = {Kim, Y and Bitna-Ha, and Kim, SW and Chang, HH and Kwon, KT and Bae, S and Hwang, S}, title = {Post-acute COVID-19 syndrome in patients after 12 months from COVID-19 infection in Korea.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {93}, pmid = {35086489}, issn = {1471-2334}, mesh = {Adolescent ; Adult ; Aged ; *COVID-19/complications ; COVID-19 Testing ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Quality of Life ; Republic of Korea/epidemiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues to progress, awareness about its long-term impacts has been growing. To date, studies on the long-term course of symptoms, factors associated with persistent symptoms, and quality of life after 12 months since recovery from acute COVID-19 have been limited.

METHODS: A prospective online survey (First: September 8, 2020-September 10, 2020; Second: May 26, 2021-June 1, 2021) was conducted on recovered patients who were previously diagnosed with COVID-19 between February 13, 2020 and March 13, 2020 at Kyungpook National University Hospital. Responders aged between 17 and 70 years were included in the study. Overall, 900 and 241 responders were followed up at 6 and 12 months after recovery from COVID-19 in the first and second surveys, respectively. Clinical characteristics, self-reported persistent symptoms, and EuroQol-5-dimension (EQ5D) index score were investigated for evaluating quality of life.

RESULTS: The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 454 (interquartile range [IQR] 451-458) days. The median age of the responders was 37 (IQR 26.0-51.0) years, and 164 (68.0%) responders were women. Altogether, 11 (4.6%) responders were asymptomatic, and 194 (80.5%), 30 (12.4%), and 6 (2.5%) responders had mild, moderate, and severe illness, respectively. Overall, 127 (52.7%) responders still experienced COVID-19-related persistent symptoms and 12 (5.0%) were receiving outpatient treatment for such symptoms. The main symptoms were difficulty in concentration, cognitive dysfunction, amnesia, depression, fatigue, and anxiety. Considering the EQ5D index scores, only 59.3% of the responders did not have anxiety or depression. Older age, female sex, and disease severity were identified as risk factors for persistent neuropsychiatric symptoms.

CONCLUSION: COVID-19-related persistent symptoms improved over time; however, neurological symptoms can last longer than other symptoms. Continuous careful observation of symptom improvement and multidisciplinary integrated research on recovered COVID-19 patients are required.}, } @article {pmid35084966, year = {2022}, author = {Couzin-Frankel, J and Vogel, G}, title = {Vaccines may cause rare, Long Covid-like symptoms.}, journal = {Science (New York, N.Y.)}, volume = {375}, number = {6579}, pages = {364-366}, doi = {10.1126/science.ada0536}, pmid = {35084966}, issn = {1095-9203}, mesh = {Animals ; Antibodies, Viral/immunology ; Autoantibodies/analysis/immunology ; COVID-19/*complications/epidemiology/etiology/immunology ; COVID-19 Vaccines/*adverse effects/immunology ; Humans ; Mice ; SARS-CoV-2/immunology ; Thrombosis/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {[Figure: see text].}, } @article {pmid35079817, year = {2022}, author = {Twomey, R and DeMars, J and Franklin, K and Culos-Reed, SN and Weatherald, J and Wrightson, JG}, title = {Chronic Fatigue and Postexertional Malaise in People Living With Long COVID: An Observational Study.}, journal = {Physical therapy}, volume = {102}, number = {4}, pages = {}, pmid = {35079817}, issn = {1538-6724}, support = {//CIHR/Canada ; }, mesh = {Adult ; *COVID-19/complications ; Cross-Sectional Studies ; *Fatigue Syndrome, Chronic ; Humans ; Quality of Life ; Symptom Flare Up ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: People living with long COVID describe a high symptom burden, and a more detailed assessment is needed to inform rehabilitation recommendations. The objectives were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of postexertional malaise (PEM); and assess symptoms of dysfunctional breathing, self-reported physical activity, and health-related quality of life.

METHODS: This was an observational study with a cross-sectional survey design (data collection from February 2021 to April 2021). Eligible participants were adults experiencing persistent symptoms due to COVID-19 that did not predate the confirmed or suspected infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the DePaul Symptom Questionnaire-Post-Exertional Malaise.

RESULTS: After data cleaning, 213 participants were included in the analysis. The total Functional Assessment of Chronic Illness Therapy-Fatigue Scale score was 18 (SD = 10) (where the score can range from 0 to 52, and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Postexertional symptom exacerbation affected most participants, and 58.7% met the PEM scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome.

CONCLUSION: Long COVID is characterized by chronic fatigue that is clinically relevant and at least as severe as fatigue in several other clinical conditions. PEM is a significant challenge for this patient group. Because of the potential for setbacks and deteriorated function following overexertion, fatigue and postexertional symptom exacerbation must be monitored and reported in clinical practice and in studies involving interventions for people with long COVID.

IMPACT: Physical therapists working with people with long COVID should measure and validate the patient's experience. Postexertional symptom exacerbation must be considered, and rehabilitation needs to be carefully designed based on individual presentation. Beneficial interventions might first ensure symptom stabilization via pacing, a self-management strategy for the activity that helps minimize postexertional malaise.}, } @article {pmid35079804, year = {2022}, author = {Acosta-Ampudia, Y and Monsalve, DM and Rojas, M and Rodríguez, Y and Zapata, E and Ramírez-Santana, C and Anaya, JM}, title = {Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome.}, journal = {The Journal of infectious diseases}, volume = {225}, number = {12}, pages = {2155-2162}, pmid = {35079804}, issn = {1537-6613}, mesh = {*Autoimmunity ; *COVID-19/complications ; Cytokines ; Humans ; Inflammation ; Interferon-gamma ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The immunopathological pathways enabling post-coronavirus disease 2019 (COVID-19) syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition.

METHODS: Thirty-three patients were included for longitudinal clinical and autoantibody analyses, 12 of whom were assessed for cytokines and lymphocyte populations. Patients were followed for 7-11 months after acute COVID-19. Autoimmune profile and immunological statuses were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry.

RESULTS: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by up-regulated interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1β, and IL-13, whereas interferon-γ-induced protein 10 (IP-10) was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of immunoglobulin G S1-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remained elevated over time.

CONCLUSIONS: The clinical manifestations of PCS are associated with the persistence of a proinflammatory and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.}, } @article {pmid35079170, year = {2022}, author = {Kreier, F}, title = {Long-COVID symptoms less likely in vaccinated people, Israeli data say.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {35079170}, issn = {1476-4687}, } @article {pmid35078982, year = {2022}, author = {Cervia, C and Zurbuchen, Y and Taeschler, P and Ballouz, T and Menges, D and Hasler, S and Adamo, S and Raeber, ME and Bächli, E and Rudiger, A and Stüssi-Helbling, M and Huber, LC and Nilsson, J and Held, U and Puhan, MA and Boyman, O}, title = {Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {446}, pmid = {35078982}, issn = {2041-1723}, support = {NRP 78 Implementation Programme//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; 4078P0-198431//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; NRP 78 Implementation Programme//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; 4078P0-198431//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; 310030-200669//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; 323530-191220//Schweizerische Akademie der Medizinischen Wissenschaften (Swiss Academy of Medical Sciences)/ ; 323530-191230//Schweizerische Akademie der Medizinischen Wissenschaften (Swiss Academy of Medical Sciences)/ ; 323530-177975//Schweizerische Akademie der Medizinischen Wissenschaften (Swiss Academy of Medical Sciences)/ ; YTCR 32/18//Schweizerische Akademie der Medizinischen Wissenschaften (Swiss Academy of Medical Sciences)/ ; YTCR 32/18//Gottfried und Julia Bangerter-Rhyner-Stiftung (Bangerter-Stiftung)/ ; }, mesh = {Adult ; Aged ; Antibodies, Viral/blood/*immunology ; COVID-19/blood/*complications/diagnosis/*immunology ; Cohort Studies ; Cough/blood/complications/immunology ; Dyspnea/blood/complications/immunology ; Fatigue/blood/complications/immunology ; Female ; Fever/blood/complications/immunology ; Humans ; Immunoglobulin G/blood/*immunology ; Immunoglobulin M/blood/*immunology ; Male ; Middle Aged ; ROC Curve ; SARS-CoV-2/*immunology/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.}, } @article {pmid35077770, year = {2022}, author = {Mariani, C and Borgonovo, F and Capetti, AF and Oreni, L and Cossu, MV and Pellicciotta, M and Armiento, L and Bocchio, S and Dedivitiis, G and Lupo, A and Galli, M and Rizzardini, G}, title = {Persistence of Long-COVID symptoms in a heterogenous prospective cohort.}, journal = {The Journal of infection}, volume = {84}, number = {5}, pages = {722-746}, pmid = {35077770}, issn = {1532-2742}, mesh = {*COVID-19/complications ; Cohort Studies ; Humans ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35077442, year = {2022}, author = {Quinn, KL and Bell, CM}, title = {Pandemic health consequences: Grasping the long COVID tail.}, journal = {PLoS medicine}, volume = {19}, number = {1}, pages = {e1003891}, pmid = {35077442}, issn = {1549-1676}, mesh = {COVID-19/*complications/epidemiology/virology ; Humans ; Pandemics/*statistics & numerical data ; SARS-CoV-2/*physiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35076368, year = {2022}, author = {Lee, H and Sung, HK and Lee, D and Choi, Y and Lee, JY and Lee, JY and Oh, MD}, title = {Comparison of Complications after Coronavirus Disease and Seasonal Influenza, South Korea.}, journal = {Emerging infectious diseases}, volume = {28}, number = {2}, pages = {347-353}, pmid = {35076368}, issn = {1080-6059}, mesh = {Adult ; *COVID-19 ; Humans ; *Influenza, Human/complications/epidemiology ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Seasons ; }, abstract = {We conducted a retrospective cohort study using claims data to determine the number and types of complications from coronavirus disease (COVID-19) that patients experience and which patients are more vulnerable to those complications compared with complications in patients with influenza. Among the cohort, 19.6% of COVID-19 patients and 28.5% of influenza patients had >1 new complication. In most complications, COVID-19 patients had lower or similar relative risk compared with influenza patients; exceptions were hair loss, heart failure, mood disorder, and dementia. Young to middle-aged adult COVID-19 patients and patients in COVID-19 hotspots had a higher risk for complications. Overall, COVID-19 patients had fewer complications than influenza patients, but caution is necessary in high-risk groups. If the fatality rate for COVID-19 is reduced through vaccination, management strategies for this disease could be adapted, similar to those for influenza management, such as easing restrictions on economic activity or requirements for close-contact isolation.}, } @article {pmid35069924, year = {2022}, author = {Kiatkittikul, P and Promteangtrong, C and Kunawudhi, A and Siripongsatian, D and Siripongboonsitti, T and Ruckpanich, P and Thongdonpua, S and Jantarato, A and Piboonvorawong, C and Fonghoi, N and Chotipanich, C}, title = {Abnormality Pattern of F-18 FDG PET Whole Body with Functional MRI Brain in Post-Acute COVID-19.}, journal = {Nuclear medicine and molecular imaging}, volume = {56}, number = {1}, pages = {29-41}, pmid = {35069924}, issn = {1869-3474}, abstract = {PURPOSE: The study aimed to investigate imaging abnormalities associated with post-acute COVID-19 using F-18 FDG PET/CT and PET/ rsfMRI brain.

METHODS: We retrospectively recruited 13 patients with post-acute COVID-19. The post-acute COVID-19 symptoms and neuropsychiatric tests were performed before F-18 FDG PET/CT whole body with PET/rsfMRI brain. Qualitative and semiquantitative analyses were also conducted in both whole body and brain images.

RESULTS: Among the 13 patients, 8 (61.5%) had myositis, followed by 8 (61.5%) with vasculitis (mainly in the thoracic aorta), and 7 (53.8%) with lung abnormalities.. Interestingly, one patient with a very high serum RBD IgG antibody demonstrated diffuse myositis throughout the body which potentially associated with immune-mediated myositis. One patient experienced psoriasis exacerbation with autoimmune-mediated after COVID-19. Most patients had multiple areas of abnormal brain connectivity involving the frontal and parieto-temporo-occipital lobes, as well as the thalamus.

CONCLUSION: The whole body F-18 FDG PET can be a potential tool to assess inflammatory process and support the hyperinflammatory etiology, mainly for lesions in skeletal muscle, vascular wall, and lung, as well as, multiple brain abnormalities in post-acute COVID-19. Nonetheless, further studies are recommended to confirm the results.}, } @article {pmid35067364, year = {2022}, author = {Heerdt, PM and Shelley, B and Singh, I}, title = {Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications.}, journal = {British journal of anaesthesia}, volume = {128}, number = {3}, pages = {e246-e249}, pmid = {35067364}, issn = {1471-6771}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; COVID-19/*complications ; Female ; Humans ; Male ; Middle Aged ; Oxygen/*metabolism ; Oxygen Consumption ; Perioperative Care ; Young Adult ; }, } @article {pmid35065779, year = {2022}, author = {Brown, K and Yahyouche, A and Haroon, S and Camaradou, J and Turner, G}, title = {Long COVID and self-management.}, journal = {Lancet (London, England)}, volume = {399}, number = {10322}, pages = {355}, pmid = {35065779}, issn = {1474-547X}, support = {MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications/therapy ; Chronic Disease/therapy ; Humans ; Observational Studies as Topic ; *Self Medication ; *Self-Management ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35065716, year = {2022}, author = {Venkatesan, P}, title = {Do vaccines protect from long COVID?.}, journal = {The Lancet. Respiratory medicine}, volume = {10}, number = {3}, pages = {e30}, doi = {10.1016/S2213-2600(22)00020-0}, pmid = {35065716}, issn = {2213-2619}, mesh = {*COVID-19/complications/prevention & control ; COVID-19 Vaccines ; Humans ; Vaccination ; *Vaccines ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35065619, year = {2022}, author = {Fortunato, F and Martinelli, D and Iannelli, G and Milazzo, M and Farina, U and Di Matteo, G and De Nittis, R and Ascatigno, L and Cassano, M and Lopalco, PL and Prato, R}, title = {Self-reported olfactory and gustatory dysfunctions in COVID-19 patients: a 1-year follow-up study in Foggia district, Italy.}, journal = {BMC infectious diseases}, volume = {22}, number = {1}, pages = {77}, pmid = {35065619}, issn = {1471-2334}, mesh = {*COVID-19 ; Follow-Up Studies ; Humans ; Italy/epidemiology ; *Olfaction Disorders/diagnosis/epidemiology/etiology ; Quality of Life ; SARS-CoV-2 ; Self Report ; Smell ; }, abstract = {BACKGROUND: From the initial stages of the pandemic in early 2020, COVID-19-related olfactory and gustatory dysfunctions have been widely reported and are emerging as one of the most frequent long-term sequelae of SARS-CoV-2 infection. However, data regarding the long-term recovery of the sense of smell and taste are lacking. This study aimed to characterize the evolution up to one year after the diagnosis of self-reported olfactory and gustatory dysfunctions in COVID-19 cases.

METHODS: Based on the data of the active surveillance platform of the Apulia region, Italy, we selected the residents of Foggia district who were confirmed positive for SARS-CoV-2 from March 1st to June 16th, 2020, and home-quarantined with paucisymptomatic-to-mild clinical presentation. Self-reported olfactory and gustatory dysfunctions were recorded at baseline through a survey of dichotomous questions. The evolution of these symptoms at approximately one year was prospectively assessed via telephone by the validated sino-nasal outcome test 22 (SNOT-22, Italian version).

RESULTS: Among the 1,175 COVID-19 cases notified in the Foggia district during the first epidemic wave, 488 had paucisymptomatic-to-mild clinical presentation. Of these, 41.2% (n = 201, 95% confidence interval [CI] 36.8-45.7%) reported at least one sensory dysfunction. A total of 178 to 201 (88.5%) patients agreed to participate in the follow-up survey. According to the SNOT-22 results, the persistence of a sensory dysfunction was observed in the 29.8% (n = 53, 95% CI 23.2-37.1%) of them. Particularly, loss of smell persisted in 25.8% (n = 46, 95% CI 19.6-32.9%), loss of taste in 21.3% (n = 38, 95% CI 15.6-28.1%), loss of both in 17.4% (n = 31, 95% CI 12.2-23.8%) of participants in the follow-up. The rates of full recovery increased over time: from 59% at 30 days to 71.9% at 90 days for the sense of smell; from 61.3% at 30 days to 74.7% at 90 days for the sense of taste.

CONCLUSIONS: The persistence of COVID-19-related olfactory and gustatory dysfunctions up to 12 months after the disease onset in a noteworthy proportion (approximately 3 out of 10) of patients with paucisymptomatic-to-mild clinical presentation deserves further investigations due to its possible pathophysiological implications and impact on the quality of life.}, } @article {pmid35062742, year = {2022}, author = {Stein, M and Ashkenazi-Hoffnung, L and Greenberg, D and Dalal, I and Livni, G and Chapnick, G and Stein-Zamir, C and Ashkenazi, S and Hecht-Sagie, L and Grossman, Z}, title = {The Burden of COVID-19 in Children and Its Prevention by Vaccination: A Joint Statement of the Israeli Pediatric Association and the Israeli Society for Pediatric Infectious Diseases.}, journal = {Vaccines}, volume = {10}, number = {1}, pages = {}, pmid = {35062742}, issn = {2076-393X}, abstract = {As of October 2021, SARS-CoV-2 infections were reported among 512,613 children and adolescents in Israel (~33% of all COVID-19 cases). The 5-11-year age group accounted for about 43% (223,850) of affected children and adolescents. In light of the availability of the Pfizer-BioNTech BNT162b2 vaccine against COVID-19 for children aged 5-11 years, we aimed to write a position paper for pediatricians, policymakers and families regarding the clinical aspects of COVID-19 and the vaccination of children against COVID-19. The first objective of this review was to describe the diverse facets of the burden of COVID-19 in children, including the direct effects of hospitalization during the acute phase of the disease, multisystem inflammatory syndrome in children, long COVID and the indirect effects of social isolation and interruption in education. In addition, we aimed to provide an update regarding the efficacy and safety of childhood mRNA COVID-19 vaccination and to instill confidence in pediatricians regarding the benefits of vaccinating children against COVID-19. We reviewed up-to-date Israeli and international epidemiological data and literature regarding COVID-19 morbidity and its sequelae in children, vaccine efficacy in reducing COVID-19-related morbidity and SARS-CoV-2 transmission and vaccine safety data. We conducted a risk-benefit analysis regarding the vaccination of children and adolescents. We concluded that vaccines are safe and effective and are recommended for all children aged 5 to 11 years to protect them from COVID-19 and its complications and to reduce community transmissions. Based on these data, after weighing the benefits of vaccination versus the harm, the Israeli Ministry of Health decided to recommend vaccination for children aged 5-11 years.}, } @article {pmid35062706, year = {2021}, author = {Scherlinger, M and Pijnenburg, L and Chatelus, E and Arnaud, L and Gottenberg, JE and Sibilia, J and Felten, R}, title = {Effect of SARS-CoV-2 Vaccination on Symptoms from Post-Acute Sequelae of COVID-19: Results from the Nationwide VAXILONG Study.}, journal = {Vaccines}, volume = {10}, number = {1}, pages = {}, pmid = {35062706}, issn = {2076-393X}, abstract = {INTRODUCTION: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC).

PATIENTS AND METHODS: We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied.

RESULTS: 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents' median age was 44 (IQR 25-75: 37-50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198-431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%).

CONCLUSION: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC.}, } @article {pmid35062027, year = {2022}, author = {Donnelly, SC}, title = {After acute there is the long-COVID syndrome: what's the plan?.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {115}, number = {1}, pages = {1-2}, doi = {10.1093/qjmed/hcab333}, pmid = {35062027}, issn = {1460-2393}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35061232, year = {2022}, author = {Fortini, A and Rosso, A and Cecchini, P and Torrigiani, A and Lo Forte, A and Carrai, P and Alessi, C and Fabbrizzi, F and Lovicu, E and Sbaragli, S and Faraone, A}, title = {One-year evolution of DLCO changes and respiratory symptoms in patients with post COVID-19 respiratory syndrome.}, journal = {Infection}, volume = {50}, number = {2}, pages = {513-517}, pmid = {35061232}, issn = {1439-0973}, mesh = {Aged ; *COVID-19/complications ; Hospitalization ; Humans ; Lung/diagnostic imaging ; Male ; Patient Discharge ; Spirometry ; }, abstract = {PURPOSE: During a follow-up program of patients admitted for COVID-19 at our non-ICU Unit, we found that 37% of them had decreased diffusing lung capacity for carbon monoxide (DLCO) 3-6 months after discharge. This prospective observational study aimed to evaluate the evolution of changes in DLCO and respiratory symptoms at the 1-year follow-up visit.

METHODS: Seventeen (mean age 71 years; 8 males) of 19 eligible patients (DLCO < 80% of predicted at the 3-6 months follow-up visit) completed the 1-year follow-up visit. One patient refused to participate and 1 patient had died 3 months earlier from myocardial infarction. The visit included a self-reported structured questionnaire, physical exam, blood tests, ECG, and spirometry with DLCO.

RESULTS: Mean DLCO was significantly improved at the 1-year visit (from 64% of predicted at 3-6 months to 74% of predicted at 1 year; P = 0.003). A clinically significant increase in DLCO (10% or greater) was observed in 11 patients (65%) with complete normalization (> 80% of predicted) in 6 (35%); in the other 6 (35%) it remained unchanged. The prevalence of exertional dyspnea (65-35%, P = 0.17), cough (24-18%, P = 1), and fatigue (76-35%, P = 0.04) decreased at the 1-year visit.

CONCLUSION: These results suggest that DLCO and respiratory symptoms tend to normalize or improve 1 year after hospitalization for COVID-19 in most patients. However, there is also a non-negligible number of patients (about one-third) in whom respiratory changes persist and will need prolonged follow-up.}, } @article {pmid35060361, year = {2022}, author = {Bungenberg, J and Humkamp, K and Hohenfeld, C and Rust, MI and Ermis, U and Dreher, M and Hartmann, NK and Marx, G and Binkofski, F and Finke, C and Schulz, JB and Costa, AS and Reetz, K}, title = {Long COVID-19: Objectifying most self-reported neurological symptoms.}, journal = {Annals of clinical and translational neurology}, volume = {9}, number = {2}, pages = {141-154}, pmid = {35060361}, issn = {2328-9503}, mesh = {Adult ; COVID-19/*complications/*physiopathology ; Cross-Sectional Studies ; Female ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Nervous System Diseases/*etiology ; *Quality of Life ; SARS-CoV-2/pathogenicity ; *Self Report ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: We aimed to objectify and compare persisting self-reported symptoms in initially hospitalized and non-hospitalized patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by applying clinical standardized measures.

METHODS: We conducted a cross-sectional study of adult patients with confirmed SARS-CoV-2 infection including medical history, neurological examination, blood markers, neuropsychological testing, patient-reported outcome measures (PROMs), and brain magnetic resonance imaging (MRI).

RESULTS: Fifty patients with persisting symptoms for at least 4 weeks were included and classified by initial hospitalization status. Median time from SARS-CoV-2 detection to investigation was 29.3 weeks (range 3.3-57.9). Although individual cognitive performance was generally within the normative range in both groups, mostly mild deficits were found in attention, executive functions, and memory. Hospitalized patients performed worse in global cognition, logical reasoning, and processes of verbal memory. In both groups, fatigue severity was associated with reduced performance in attention and psychomotor speed tasks (rs  = -0.40, p < 0.05) and reduced quality of life (EQ5D, rs  = 0.57, p < 0.001) and with more persisting symptoms (median 3 vs. 6, p < 0.01). PROMs identified fatigue, reduced sleep quality, and increased anxiety and depression in both groups but more pronounced in non-hospitalized patients. Brain MRI revealed microbleeds exclusively in hospitalized patients (n = 5).

INTERPRETATION: Regardless of initial COVID-19 severity, an individuals' mental and physical health can be severely impaired in the long-term limitedly objectified by clinical standard diagnostic with abnormalities primarily found in hospitalized patients. This needs to be considered when planning rehabilitation therapies and should give rise to new biomarker research.}, } @article {pmid35059902, year = {2022}, author = {Mirfazeli, FS and Sarabi-Jamab, A and Pereira-Sanchez, V and Kordi, A and Shariati, B and Shariat, SV and Bahrami, S and Nohesara, S and Almasi-Dooghaee, M and Faiz, SHR}, title = {Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {43}, number = {4}, pages = {2231-2239}, pmid = {35059902}, issn = {1590-3478}, mesh = {*COVID-19/complications ; Cognition ; *Fatigue Syndrome, Chronic/complications ; Female ; Follow-Up Studies ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The preva lence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We followed up 95 patients with confirmed COVID-19 for 9 months to identify and characterize long-COVID symptoms. Easy fatigability was the most common symptom (51.04%), followed by anxiety (38.54%), dyspnea (38.54%), and new-onset headache (38.54%). There was no association between COVID-19 severity in the acute phase and the number of long-COVID symptoms (F(1,93) = 0.75, p = 0.45), and cognitive function (MoCA) scores (F(1,90) = 0.073, p = 0.787) at follow-up. Being female (F(1,92) = - 2.27, p = 0.02), having a higher number of symptoms (F(1,93) = 2.76, p = 0.0068), and experiencing constitutional neuropsychiatric symptoms (F(1,93) = 2.529, p = 0.01) in the acute phase were associated with having chronic fatigue syndrome at follow-up. Moreover, constitutional neuropsychiatric symptoms in the acute phase were associated with a lower MoCA score (F(1,93) = 10.84, p = 0.001) at follow-up. Specific clinical presentations such as constitutional neuropsychiatric symptoms in the acute phase might be predictors of debilitating long-COVID symptoms such as chronic fatigue syndrome and cognitive deficits.}, } @article {pmid35059730, year = {2022}, author = {Geronikolou, SA and Takan, I and Pavlopoulou, A and Mantzourani, M and Chrousos, GP}, title = {Thrombocytopenia in COVID‑19 and vaccine‑induced thrombotic thrombocytopenia.}, journal = {International journal of molecular medicine}, volume = {49}, number = {3}, pages = {}, pmid = {35059730}, issn = {1791-244X}, mesh = {Artificial Intelligence ; *COVID-19/complications ; COVID-19 Vaccines/adverse effects ; Humans ; SARS-CoV-2 ; *Thrombocytopenia/chemically induced/genetics ; *Thrombosis/genetics ; *Vaccines ; Post-Acute COVID-19 Syndrome ; }, abstract = {The highly heterogeneous symptomatology and unpredictable progress of COVID‑19 triggered unprecedented intensive biomedical research and a number of clinical research projects. Although the pathophysiology of the disease is being progressively clarified, its complexity remains vast. Moreover, some extremely infrequent cases of thrombotic thrombocytopenia following vaccination against SARS‑CoV‑2 infection have been observed. The present study aimed to map the signaling pathways of thrombocytopenia implicated in COVID‑19, as well as in vaccine‑induced thrombotic thrombocytopenia (VITT). The biomedical literature database, MEDLINE/PubMed, was thoroughly searched using artificial intelligence techniques for the semantic relations among the top 50 similar words (>0.9) implicated in COVID‑19‑mediated human infection or VITT. Additionally, STRING, a database of primary and predicted associations among genes and proteins (collected from diverse resources, such as documented pathway knowledge, high‑throughput experimental studies, cross‑species extrapolated information, automated text mining results, computationally predicted interactions, etc.), was employed, with the confidence threshold set at 0.7. In addition, two interactomes were constructed: i) A network including 119 and 56 nodes relevant to COVID‑19 and thrombocytopenia, respectively; and ii) a second network containing 60 nodes relevant to VITT. Although thrombocytopenia is a dominant morbidity in both entities, three nodes were observed that corresponded to genes (AURKA, CD46 and CD19) expressed only in VITT, whilst ADAM10, CDC20, SHC1 and STXBP2 are silenced in VITT, but are commonly expressed in both COVID‑19 and thrombocytopenia. The calculated average node degree was immense (11.9 in COVID‑19 and 6.43 in VITT), illustrating the complexity of COVID‑19 and VITT pathologies and confirming the importance of cytokines, as well as of pathways activated following hypoxic events. In addition, PYCARD, NLP3 and P2RX7 are key potential therapeutic targets for all three morbid entities, meriting further research. This interactome was based on wild‑type genes, revealing the predisposition of the body to hypoxia‑induced thrombosis, leading to the acute COVID‑19 phenotype, the 'long‑COVID syndrome', and/or VITT. Thus, common nodes appear to be key players in illness prevention, progression and treatment.}, } @article {pmid35059196, year = {2022}, author = {Wong-Chew, RM and Rodríguez Cabrera, EX and Rodríguez Valdez, CA and Lomelin-Gascon, J and Morales-Juárez, L and de la Cerda, MLR and Villa-Romero, AR and Arce Fernández, S and Serratos Fernandez, M and Bello, HH and Castañeda, LM and Avendaño, MA and Hernández-Cruz, JA and Álvarez Martínez, N and Fernanda Contreras, L and Rafael González de la Cerda, L and Juárez Flores, A and Martínez-Juarez, LA and Álvarez-Hernández, DA and Gallardo-Rincón, H and Fajardo Dolci, G and Tapia-Conyer, R and Valdez-Vázquez, RR}, title = {Symptom cluster analysis of long COVID-19 in patients discharged from the Temporary COVID-19 Hospital in Mexico City.}, journal = {Therapeutic advances in infectious disease}, volume = {9}, number = {}, pages = {20499361211069264}, pmid = {35059196}, issn = {2049-9361}, abstract = {INTRODUCTION: Several reports have emerged describing the long-term consequences of COVID-19 and its effects on multiple systems.

METHODS: As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of the long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal).

RESULTS: We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p < 0.00001). Women were more prone than men to develop long-term symptoms, and invasive mechanical ventilation also increased the frequency of symptoms at 30 days post-discharge.

CONCLUSION: Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.}, } @article {pmid35058281, year = {2022}, author = {Zimmermann, P and Pittet, LF and Curtis, N}, title = {Long covid in children and adolescents.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o143}, doi = {10.1136/bmj.o143}, pmid = {35058281}, issn = {1756-1833}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Humans ; Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35058230, year = {2022}, author = {Baraniuk, C}, title = {Covid-19: How Europe is approaching long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {376}, number = {}, pages = {o158}, doi = {10.1136/bmj.o158}, pmid = {35058230}, issn = {1756-1833}, } @article {pmid35057809, year = {2022}, author = {Jarius, S and Pache, F and Körtvelyessy, P and Jelčić, I and Stettner, M and Franciotta, D and Keller, E and Neumann, B and Ringelstein, M and Senel, M and Regeniter, A and Kalantzis, R and Willms, JF and Berthele, A and Busch, M and Capobianco, M and Eisele, A and Reichen, I and Dersch, R and Rauer, S and Sandner, K and Ayzenberg, I and Gross, CC and Hegen, H and Khalil, M and Kleiter, I and Lenhard, T and Haas, J and Aktas, O and Angstwurm, K and Kleinschnitz, C and Lewerenz, J and Tumani, H and Paul, F and Stangel, M and Ruprecht, K and Wildemann, B and , }, title = {Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.}, journal = {Journal of neuroinflammation}, volume = {19}, number = {1}, pages = {19}, pmid = {35057809}, issn = {1742-2094}, support = {1499 TG93 U1//Ministry for Education and Research Baden-Württemberg, Germany/ ; 4078P0_198345/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {Adult ; Blood-Brain Barrier ; COVID-19/*cerebrospinal fluid/complications ; Cerebrospinal Fluid Proteins/cerebrospinal fluid ; Cytokines/cerebrospinal fluid ; Europe ; Female ; Humans ; Immunity, Cellular ; Immunoglobulin G/cerebrospinal fluid ; Lactic Acid/cerebrospinal fluid ; Leukocyte Count ; Male ; Middle Aged ; Nervous System Diseases/cerebrospinal fluid/etiology ; Oligoclonal Bands/cerebrospinal fluid ; Retrospective Studies ; Spinal Puncture ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far.

OBJECTIVE: To analyze systematically the CSF profile in COVID-19.

METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease.

CONCLUSIONS: The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.}, } @article {pmid35056324, year = {2021}, author = {Hayden, MR and Tyagi, SC}, title = {Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer's Disease and Long COVID.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {58}, number = {1}, pages = {}, pmid = {35056324}, issn = {1648-9144}, mesh = {*Alzheimer Disease ; *COVID-19/complications ; Carbon ; *Diabetes Mellitus, Type 2 ; Folic Acid ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Impaired folate-mediated one-carbon metabolism (FOCM) is associated with many pathologies and developmental abnormalities. FOCM is a metabolic network of interdependent biosynthetic pathways that is known to be compartmentalized in the cytoplasm, mitochondria and nucleus. Currently, the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be fully established. This review specifically examines the role of impaired FOCM in type 2 diabetes mellitus, Alzheimer's disease and the emerging Long COVID/post-acute sequelae of SARS-CoV-2 (PASC). Importantly, elevated homocysteine may be considered a biomarker for impaired FOCM, which is known to result in increased oxidative-redox stress. Therefore, the incorporation of hyperhomocysteinemia will be discussed in relation to impaired FOCM in each of the previously listed clinical diseases. This review is intended to fill gaps in knowledge associated with these clinical diseases and impaired FOCM. Additionally, some of the therapeutics will be discussed at this early time point in studying impaired FOCM in each of the above clinical disease states. It is hoped that this review will allow the reader to better understand the role of FOCM in the development and treatment of clinical disease states that may be associated with impaired FOCM and how to restore a more normal functional role for FOCM through improved nutrition and/or restoring the essential water-soluble B vitamins through oral supplementation.}, } @article {pmid35054906, year = {2022}, author = {Lauwers, M and Au, M and Yuan, S and Wen, C}, title = {COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives.}, journal = {International journal of molecular sciences}, volume = {23}, number = {2}, pages = {}, pmid = {35054906}, issn = {1422-0067}, mesh = {Adipose Tissue/metabolism/physiopathology ; *Aging ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/complications/*pathology/virology ; Humans ; Musculoskeletal System/metabolism/physiopathology ; Osteoarthritis/complications/*pathology ; Pain/etiology ; Renin-Angiotensin System ; SARS-CoV-2/isolation & purification ; }, abstract = {COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.}, } @article {pmid35054224, year = {2021}, author = {Luchian, ML and Motoc, A and Lochy, S and Magne, J and Belsack, D and De Mey, J and Roosens, B and Van den Bussche, K and Boeckstaens, S and Chameleva, H and Geers, J and Houard, L and De Potter, T and Allard, S and Weytjens, C and Droogmans, S and Cosyns, B}, title = {Subclinical Myocardial Dysfunction in Patients with Persistent Dyspnea One Year after COVID-19.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054224}, issn = {2075-4418}, abstract = {Long coronavirus disease 2019 (COVID-19) was described in patients recovering from COVID-19, with dyspnea being a frequent symptom. Data regarding the potential mechanisms of long COVID remain scarce. We investigated the presence of subclinical cardiac dysfunction, assessed by transthoracic echocardiography (TTE), in recovered COVID-19 patients with or without dyspnea, after exclusion of previous cardiopulmonary diseases. A total of 310 consecutive COVID-19 patients were prospectively included. Of those, 66 patients (mean age 51.3 ± 11.1 years, almost 60% males) without known cardiopulmonary diseases underwent one-year follow-up consisting of clinical evaluation, spirometry, chest computed tomography, and TTE. From there, 23 (34.8%) patients reported dyspnea. Left ventricle (LV) ejection fraction was not significantly different between patients with or without dyspnea (55.7 ± 4.6 versus (vs.) 57.6 ± 4.5, p = 0.131). Patients with dyspnea presented lower LV global longitudinal strain, global constructive work (GCW), and global work index (GWI) compared to asymptomatic patients (-19.9 ± 2.1 vs. -21.3 ± 2.3 p = 0.039; 2183.7 ± 487.9 vs. 2483.1 ± 422.4, p = 0.024; 1960.0 ± 396.2 vs. 2221.1 ± 407.9, p = 0.030). GCW and GWI were inversely and independently associated with dyspnea (p = 0.035, OR 0.998, 95% CI 0.997-1.000; p = 0.040, OR 0.998, 95% CI 0.997-1.000). Persistent dyspnea one-year after COVID-19 was present in more than a third of the recovered patients. GCW and GWI were the only echocardiographic parameters independently associated with symptoms, suggesting a decrease in myocardial performance and subclinical cardiac dysfunction.}, } @article {pmid35054108, year = {2022}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Pellicer-Valero, ÓJ and Navarro-Pardo, E and Gómez-Mayordomo, V and Cuadrado, ML and Arias-Navalón, JA and Cigarán-Méndez, M and Hernández-Barrera, V and Arendt-Nielsen, L}, title = {Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study.}, journal = {Journal of clinical medicine}, volume = {11}, number = {2}, pages = {}, pmid = {35054108}, issn = {2077-0383}, support = {NNF21OC0067235//Novo Nordisk Foundation/ ; The LONG-COVID-EXP-CM//Comunidad de Madrid/ ; }, abstract = {This multicenter cohort study investigated the differences between coronavirus disease 2019 (COVID-19) related symptoms and post-COVID symptoms between male and female COVID-19 survivors. Clinical and hospitalization data were collected from hospital medical records in a sample of individuals recovered from COVID-19 at five public hospitals in Spain. A predefined list of post-COVID symptoms was systematically assessed, but patients were free to report any symptom. Anxiety/depressive levels and sleep quality were also assessed. Adjusted multivariate logistic regressions were used to identify the association of sex with post-COVID related-symptoms. A total of 1969 individuals (age: 61, SD: 16 years, 46.4% women) were assessed 8.4 months after discharge. No overall significant sex differences in COVID-19 onset symptoms at hospital admission were found. Post-COVID symptoms were present in up to 60% of hospitalized COVID-19 survivors eight months after the infection. The number of post-COVID symptoms was 2.25 for females and 1.5 for males. After adjusting by all variables, female sex was associated with ≥3 post-COVID symptoms (adj OR 2.54, 95%CI 1.671-3.865, p < 0.001), the presence of post-COVID fatigue (adj OR 1.514, 95%CI 1.040-2.205), dyspnea (rest: adj OR 1.428, 95%CI 1.081-1.886, exertion: adj OR 1.409, 95%CI 1.109-1.791), pain (adj OR 1.349, 95%CI 1.059-1.720), hair loss (adj OR 4.529, 95%CI 2.784-7.368), ocular problems (adj OR 1.981, 95%CI 1.185-3.312), depressive levels (adj OR 1.606, 95%CI 1.002-2.572) and worse sleep quality (adj OR 1.634, 95%CI 1.097-2.434). Female sex was a risk factor for the development of some long-term post-COVID symptoms including mood disorders. Healthcare systems should consider sex differences in the management of long haulers.}, } @article {pmid35053059, year = {2022}, author = {Thye, AY and Law, JW and Tan, LT and Pusparajah, P and Ser, HL and Thurairajasingam, S and Letchumanan, V and Lee, LH}, title = {Psychological Symptoms in COVID-19 Patients: Insights into Pathophysiology and Risk Factors of Long COVID-19.}, journal = {Biology}, volume = {11}, number = {1}, pages = {}, pmid = {35053059}, issn = {2079-7737}, support = {FRGS/1/2019/SKK08/MUSM/02/7//Fundamental Research Grant Scheme/ ; MBRS/JCSMHS/02/2020//SEED Funding from Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences/ ; }, abstract = {There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.}, } @article {pmid35052628, year = {2022}, author = {Satoh, T and Trudler, D and Oh, CK and Lipton, SA}, title = {Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35052628}, issn = {2076-3921}, support = {R35 AG071734/AG/NIA NIH HHS/United States ; R01 AG078756/AG/NIA NIH HHS/United States ; R01 AG056259/AG/NIA NIH HHS/United States ; RF1 AG057409, R01 AG056259, R01 DA048882, R01 NS086890 and DP1 DA041722//NIH grants/ ; DISC2 COVID19-11811, and a COVID-19 award from Fast Grants//California Institute for Regenerative Medicine (CIRM) grant/ ; R01 DA048882/DA/NIDA NIH HHS/United States ; RF1 AG057409/AG/NIA NIH HHS/United States ; }, abstract = {Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer's disease (AD), Parkinson's disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed "long-COVID." One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and "brain fog" are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood-brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.}, } @article {pmid35043334, year = {2022}, author = {Grund, S and Bauer, J}, title = {[Long COVID Syndrome in frail older persons - complex to diagnose and treat].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {1}, pages = {42-47}, doi = {10.1007/s15006-021-0575-3}, pmid = {35043334}, issn = {1613-3560}, mesh = {Aged ; Aged, 80 and over ; *COVID-19/complications ; Frail Elderly ; Geriatric Assessment ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35043333, year = {2022}, author = {Bisenius, S and Kersting, A}, title = {[Psychosomatic aspects of Long COVID].}, journal = {MMW Fortschritte der Medizin}, volume = {164}, number = {1}, pages = {40-41}, doi = {10.1007/s15006-021-0540-1}, pmid = {35043333}, issn = {1613-3560}, mesh = {*COVID-19/complications/psychology ; Humans ; *Psychophysiologic Disorders/diagnosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35043113, year = {2022}, author = {Fernández-Castañeda, A and Lu, P and Geraghty, AC and Song, E and Lee, MH and Wood, J and Yalçın, B and Taylor, KR and Dutton, S and Acosta-Alvarez, L and Ni, L and Contreras-Esquivel, D and Gehlhausen, JR and Klein, J and Lucas, C and Mao, T and Silva, J and Peña-Hernández, MA and Tabachnikova, A and Takahashi, T and Tabacof, L and Tosto-Mancuso, J and Breyman, E and Kontorovich, A and McCarthy, D and Quezado, M and Hefti, M and Perl, D and Folkerth, R and Putrino, D and Nath, A and Iwasaki, A and Monje, M}, title = {Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {35043113}, issn = {2692-8205}, support = {DP1 NS111132/NS/NINDS NIH HHS/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01 NS092597/NS/NINDS NIH HHS/United States ; T32 AR007016/AR/NIAMS NIH HHS/United States ; }, abstract = {Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection - without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.}, } @article {pmid35039086, year = {2022}, author = {Zha, M and Chaffee, K and Alsarraj, J}, title = {Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report.}, journal = {Journal of medical case reports}, volume = {16}, number = {1}, pages = {31}, pmid = {35039086}, issn = {1752-1947}, mesh = {*COVID-19/complications ; *Dry Needling ; Humans ; Male ; Middle Aged ; Myalgia ; SARS-CoV-2 ; Trigger Points ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Myofascial pain is a complex health condition that affects the majority of the general population. Myalgia has been recognized as a symptom of long COVID syndrome. The treatment for long COVID syndrome-related myalgia lacks research. Dry needling is a technique that involves the insertion of a needle into the tissue of, or overlaying, a pain point. Wet needling is the addition of an injection of an analgesic substance such as lidocaine while performing needling. Both dry and wet needling have are practiced as treatment modalities for myofascial pain. Limited literature exists to define long COVID syndrome-related myalgia and its relation to myofascial pain, or to examine the utility of needling techniques for this pain. We report a case of dry and wet needling as effective treatments for long COVID-related myofascial pain.

CASE PRESENTATION: A 59-year-old, previously healthy Hispanic male with no comorbid conditions was diagnosed with COVID-19 pneumonia. The patient suffered moderate disease without hypoxia and was never hospitalized. Three months later, the patient continued to suffer from symptoms such as exertional dyspnea, "brain fog," and myalgia. An extensive multisystem workup revealed normal cardiac, pulmonary, and end organ functions. The patient was then diagnosed with long COVID syndrome. The nature and chronicity of the patient's myalgia meet the criteria for myofascial pain. Both wet and dry needling were used to treat the patient's myofascial pain, with good short- and long-term therapeutic effects.

CONCLUSIONS: COVID-19 infection has been shown to exacerbate preexisting myofascial pain syndrome. Our case report indicates that long COVID syndrome-related myalgia is likely a form of new-onset myofascial pain. Additionally, both wet and dry needling can be utilized as an effective treatment modality for this pain syndrome, with short- and long-term benefits.}, } @article {pmid35038898, year = {2022}, author = {Gamage, AM and Tan, KS and Chan, WOY and Lew, ZZR and Liu, J and Tan, CW and Rajagopalan, D and Lin, QXX and Tan, LM and Venkatesh, PN and Ong, YK and Thong, M and Lin, RTP and Prabhakar, S and Wang, Y and Wang, LF}, title = {Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection In Vitro, despite Eliciting a Prolonged Antiviral Response.}, journal = {mBio}, volume = {13}, number = {1}, pages = {e0343621}, pmid = {35038898}, issn = {2150-7511}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Epithelial Cells ; Antiviral Agents ; }, abstract = {The dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia. IMPORTANCE Increasing medical attention has been drawn to the persistence of symptoms (long-COVID syndrome) or live virus shedding from subsets of COVID-19 patients weeks to months after the initial onset of symptoms. In vitro approaches to model viral or symptom persistence are needed to fully dissect the complex and likely varied mechanisms underlying these clinical observations. We show that in vitro differentiated human NECs are persistently infected with SARS-CoV-2 for up to 28 dpi. This viral replication occurred despite the presence of an antiviral gene signature across all NEC cell types even at 28 dpi. This indicates that epithelial cell intrinsic antiviral responses are insufficient for the clearance of SARS-CoV-2, implying an essential role for tissue-resident and infiltrating immune cells for eventual viral clearance from infected airway tissue in COVID-19 patients.}, } @article {pmid35038258, year = {2021}, author = {Adeniyi, BO and Akinwalere, O and Erhabor, GE}, title = {Long COVID in Nigeria Beyond the Epidemic, Making Adequate Preparations for the Long-Term Effects of COVID-19.}, journal = {West African journal of medicine}, volume = {38}, number = {12}, pages = {1247-1248}, pmid = {35038258}, issn = {0189-160X}, mesh = {*COVID-19/complications ; Humans ; Nigeria ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35032963, year = {2022}, author = {Clerbaux, LA and Amigó, N and Amorim, MJ and Bal-Price, A and Batista Leite, S and Beronius, A and Bezemer, GFG and Bostroem, AC and Carusi, A and Coecke, S and Concha, R and Daskalopoulos, EP and De Bernardi, F and Edrosa, E and Edwards, SW and Filipovska, J and Garcia-Reyero, N and Gavins, FNE and Halappanavar, S and Hargreaves, AJ and Hogberg, HT and Huynh, MT and Jacobson, D and Josephs-Spaulding, J and Kim, YJ and Kong, HJ and Krebs, CE and Lam, A and Landesmann, B and Layton, A and Lee, YO and Macmillan, DS and Mantovani, A and Margiotta-Casaluci, L and Martens, M and Masereeuw, R and Mayasich, SA and Mei, LM and Mortensen, H and Munoz Pineiro, A and Nymark, P and Ohayon, E and Ojasi, J and Paini, A and Parissis, N and Parvatam, S and Pistollato, F and Sachana, M and Sørli, JB and Sullivan, KM and Sund, J and Tanabe, S and Tsaioun, K and Vinken, M and Viviani, L and Waspe, J and Willett, C and Wittwehr, C}, title = {COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop.}, journal = {ALTEX}, volume = {39}, number = {2}, pages = {322–335}, pmid = {35032963}, issn = {1868-8551}, support = {EPA999999/ImEPA/Intramural EPA/United States ; RF1 AG053303/AG/NIA NIH HHS/United States ; }, mesh = {*Adverse Outcome Pathways ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {On April 28-29, 2021, 50 scientists from different fields of expertise met for the 3rd online CIAO workshop. The CIAO project “Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework” aims at building a holistic assembly of the available scientific knowledge on COVID-19 using the AOP framework. An individual AOP depicts the disease progression from the initial contact with the SARS-CoV-2 virus through biological key events (KE) toward an adverse outcome such as respiratory distress, anosmia or multiorgan failure. Assembling the individual AOPs into a network highlights shared KEs as central biological nodes involved in multiple outcomes observed in COVID-19 patients. During the workshop, the KEs and AOPs established so far by the CIAO members were presented and posi­tioned on a timeline of the disease course. Modulating factors influencing the progression and severity of the disease were also addressed as well as factors beyond purely biological phenomena. CIAO relies on an interdisciplinary crowd­sourcing effort, therefore, approaches to expand the CIAO network by widening the crowd and reaching stakeholders were also discussed. To conclude the workshop, it was decided that the AOPs/KEs will be further consolidated, inte­grating virus variants and long COVID when relevant, while an outreach campaign will be launched to broaden the CIAO scientific crowd.}, } @article {pmid35032430, year = {2022}, author = {Jansen, J and Reimer, KC and Nagai, JS and Varghese, FS and Overheul, GJ and de Beer, M and Roverts, R and Daviran, D and Fermin, LAS and Willemsen, B and Beukenboom, M and Djudjaj, S and von Stillfried, S and van Eijk, LE and Mastik, M and Bulthuis, M and Dunnen, WD and van Goor, H and Hillebrands, JL and Triana, SH and Alexandrov, T and Timm, MC and van den Berge, BT and van den Broek, M and Nlandu, Q and Heijnert, J and Bindels, EMJ and Hoogenboezem, RM and Mooren, F and Kuppe, C and Miesen, P and Grünberg, K and Ijzermans, T and Steenbergen, EJ and Czogalla, J and Schreuder, MF and Sommerdijk, N and Akiva, A and Boor, P and Puelles, VG and Floege, J and Huber, TB and , and van Rij, RP and Costa, IG and Schneider, RK and Smeets, B and Kramann, R}, title = {SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids.}, journal = {Cell stem cell}, volume = {29}, number = {2}, pages = {217-231.e8}, pmid = {35032430}, issn = {1875-9777}, mesh = {*COVID-19/complications ; Fibrosis ; Humans ; Kidney ; Organoids/pathology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.}, } @article {pmid35031121, year = {2022}, author = {Valdes, E and Fuchs, B and Morrison, C and Charvet, L and Lewis, A and Thawani, S and Balcer, L and Galetta, SL and Wisniewski, T and Frontera, JA}, title = {Demographic and social determinants of cognitive dysfunction following hospitalization for COVID-19.}, journal = {Journal of the neurological sciences}, volume = {438}, number = {}, pages = {120146}, pmid = {35031121}, issn = {1878-5883}, support = {P01 AG060882/AG/NIA NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; }, mesh = {*COVID-19/complications/epidemiology ; *Cognitive Dysfunction/diagnosis/epidemiology/etiology ; *Dementia/complications ; Hospitalization ; Humans ; Prospective Studies ; SARS-CoV-2 ; Social Determinants of Health ; }, abstract = {BACKGROUND: Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19.

METHODS: We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA.

RESULTS: Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition.

CONCLUSIONS: Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.}, } @article {pmid35029046, year = {2022}, author = {Jarrott, B and Head, R and Pringle, KG and Lumbers, ER and Martin, JH}, title = {"LONG COVID"-A hypothesis for understanding the biological basis and pharmacological treatment strategy.}, journal = {Pharmacology research & perspectives}, volume = {10}, number = {1}, pages = {e00911}, pmid = {35029046}, issn = {2052-1707}, mesh = {Antiviral Agents/*therapeutic use ; Biomarkers/metabolism ; COVID-19/*complications/physiopathology/virology ; Endothelium, Vascular/virology ; Humans ; SARS-CoV-2/isolation & purification/physiology ; Virus Replication ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as "COVID-19" with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, "brain fog," insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named "LONG COVID." Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively. It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in "LONG COVID" subjects experiencing insomnia, depression, fatigue, and "brain fog" but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.}, } @article {pmid35028901, year = {2022}, author = {Theoharides, TC}, title = {Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome?.}, journal = {Molecular neurobiology}, volume = {59}, number = {3}, pages = {1850-1861}, pmid = {35028901}, issn = {1559-1182}, mesh = {COVID-19/*complications/etiology/virology ; Humans ; Prospective Studies ; Spike Glycoprotein, Coronavirus/*physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 infects cells via its spike protein binding to its surface receptor on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that many patients develop a chronic condition characterized by fatigue and neuropsychiatric symptoms, termed long-COVID. Most of the vaccines produced so far for COVID-19 direct mammalian cells via either mRNA or an adenovirus vector to express the spike protein, or administer recombinant spike protein, which is recognized by the immune system leading to the production of neutralizing antibodies. Recent publications provide new findings that may help decipher the pathogenesis of long-COVID. One paper reported perivascular inflammation in brains of deceased patients with COVID-19, while others showed that the spike protein could damage the endothelium in an animal model, that it could disrupt an in vitro model of the blood-brain barrier (BBB), and that it can cross the BBB resulting in perivascular inflammation. Moreover, the spike protein appears to share antigenic epitopes with human molecular chaperons resulting in autoimmunity and can activate toll-like receptors (TLRs), leading to release of inflammatory cytokines. Moreover, some antibodies produced against the spike protein may not be neutralizing, but may change its conformation rendering it more likely to bind to its receptor. As a result, one wonders whether the spike protein entering the brain or being expressed by brain cells could activate microglia, alone or together with inflammatory cytokines, since protective antibodies could not cross the BBB, leading to neuro-inflammation and contributing to long-COVID. Hence, there is urgent need to better understand the neurotoxic effects of the spike protein and to consider possible interventions to mitigate spike protein-related detrimental effects to the brain, possibly via use of small natural molecules, especially the flavonoids luteolin and quercetin.}, } @article {pmid35027728, year = {2022}, author = {Phetsouphanh, C and Darley, DR and Wilson, DB and Howe, A and Munier, CML and Patel, SK and Juno, JA and Burrell, LM and Kent, SJ and Dore, GJ and Kelleher, AD and Matthews, GV}, title = {Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection.}, journal = {Nature immunology}, volume = {23}, number = {2}, pages = {210-216}, pmid = {35027728}, issn = {1529-2916}, support = {1902854//NSF | Directorate for Mathematical & Physical Sciences | Division of Mathematical Sciences (DMS)/ ; 1055214//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1123673//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1136322//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1149990//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Adult ; Aged ; B-Lymphocytes/*immunology/metabolism/virology ; Biomarkers/blood ; COVID-19/blood/*complications/immunology/virology ; Case-Control Studies ; Cytokines/blood ; Female ; Host-Pathogen Interactions ; Humans ; *Immunity, Innate ; Inflammation Mediators/blood ; Male ; Middle Aged ; Prognosis ; SARS-CoV-2/*immunology/pathogenicity ; Severity of Illness Index ; T-Lymphocytes/*immunology/metabolism/virology ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-β, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.}, } @article {pmid35027428, year = {2022}, author = {Philip, KEJ and Buttery, S and Williams, P and Vijayakumar, B and Tonkin, J and Cumella, A and Renwick, L and Ogden, L and Quint, JK and Johnston, SL and Polkey, MI and Hopkinson, NS}, title = {Impact of COVID-19 on people with asthma: a mixed methods analysis from a UK wide survey.}, journal = {BMJ open respiratory research}, volume = {9}, number = {1}, pages = {}, pmid = {35027428}, issn = {2052-4439}, mesh = {*Asthma/drug therapy/epidemiology ; *COVID-19/complications ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The impact of acute COVID-19 on people with asthma appears complex, being moderated by multiple interacting disease-specific, demographic and environmental factors. Research regarding longer-term effects in this group is limited. We aimed to assess impacts of COVID-19 and predictors of persistent symptoms, in people with asthma.

METHODS: Using data from an online UK-wide survey of 4500 people with asthma (median age 50-59 years, 81% female), conducted in October 2020, we undertook a mixed methods analysis of the characteristics and experience of those reporting having had COVID-19.

RESULTS: The COVID-19 group (n=471, 10.5%) reported increased inhaler use and worse asthma management, compared with those not reporting COVID-19, but did not differ by gender, ethnicity or household income. Among the COVID-19 group, 56.1% reported having long COVID, 20.2% were 'unsure'. Those with long COVID were more likely than those without long COVID to describe: their breathing as worse or much worse after their initial illness (73.7% vs 34.8%, p<0.001), increased inhaler use (67.8% vs 34.8%, p<0.001) and worse or much worse asthma management (59.6% vs 25.6%, p<0.001). Having long COVID was not associated with age, gender, ethnicity, UK nation or household income.Analysis of free text survey responses identified three key themes: (1) variable COVID-19 severity, duration and recovery; (2) symptom overlap and interaction between COVID-19 and asthma; (3) barriers to accessing healthcare.

CONCLUSIONS: Persisting symptoms are common in people with asthma following COVID-19. Measures are needed to ensure appropriate healthcare access including clinical evaluation and investigation, to distinguish between COVID-19 symptoms and asthma.}, } @article {pmid35027067, year = {2022}, author = {Ryan, FJ and Hope, CM and Masavuli, MG and Lynn, MA and Mekonnen, ZA and Yeow, AEL and Garcia-Valtanen, P and Al-Delfi, Z and Gummow, J and Ferguson, C and O'Connor, S and Reddi, BAJ and Hissaria, P and Shaw, D and Kok-Lim, C and Gleadle, JM and Beard, MR and Barry, SC and Grubor-Bauk, B and Lynn, DJ}, title = {Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection.}, journal = {BMC medicine}, volume = {20}, number = {1}, pages = {26}, pmid = {35027067}, issn = {1741-7015}, mesh = {Antibodies, Viral ; *COVID-19/complications ; Humans ; Immune System ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.

METHODS: We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.

RESULTS: Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.

CONCLUSIONS: Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.}, } @article {pmid35023454, year = {2022}, author = {Haberland, A and Müller, J}, title = {Aptamers Against COVID-19: An Untested Opportunity.}, journal = {Mini reviews in medicinal chemistry}, volume = {22}, number = {13}, pages = {1708-1715}, pmid = {35023454}, issn = {1875-5607}, mesh = {Antiviral Agents/pharmacology/therapeutic use ; *COVID-19/complications ; Drug Repositioning ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {Given the lack of success in the development of effective drugs to treat COVID-19, which show "game-changing" potential, it is necessary to explore drugs with different modes of action. Single mode-of-action drugs have not been succeeded in curing COVID-19, which is a highly complex disease. This is the case for direct antivirals and anti-inflammatory drugs, both of which treat different phases of the disease. Aptamers are molecules that deliver different modes of action, allowing their effects to be bundled, which, when combined, support their therapeutic efficacy. In this minireview, we summarise the current activities in the development of aptamers for the treatment of COVID-19 and long-COVID. A special emphasis is placed on the capability of their multiple modes of action, which is a promising approach for treating complex diseases such as COVID-19.}, } @article {pmid35020945, year = {2022}, author = {}, title = {Does anti-viral treatment in acute COVID infection decrease the risk of developing the Long-COVID Syndrome?.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {114}, number = {12}, pages = {841-842}, doi = {10.1093/qjmed/hcab319}, pmid = {35020945}, issn = {1460-2393}, mesh = {Antiviral Agents/therapeutic use ; *COVID-19/complications ; Humans ; *Infections ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35019862, year = {2022}, author = {Rebello, CJ and Axelrod, CL and Reynolds, CF and Greenway, FL and Kirwan, JP}, title = {Exercise as a Moderator of Persistent Neuroendocrine Symptoms of COVID-19.}, journal = {Exercise and sport sciences reviews}, volume = {50}, number = {2}, pages = {65-72}, pmid = {35019862}, issn = {1538-3008}, support = {K99 AG065419/AG/NIA NIH HHS/United States ; R00 AG065419/AG/NIA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {Brain ; *COVID-19/complications ; Disease Progression ; Exercise ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Precipitated by chronic psychological stress, immune system dysregulation, and a hyperinflammatory state, the sequelae of postacute COVID-19 (long COVID) include depression and new-onset diabetes. We hypothesize that exercise counters the neuropsychiatric and endocrine sequelae of long COVID by inducing the release of circulating factors that mediate the anti-inflammatory response, support brain homeostasis, and increase insulin sensitivity.}, } @article {pmid35017239, year = {2022}, author = {Macpherson, K and Cooper, K and Harbour, J and Mahal, D and Miller, C and Nairn, M}, title = {Experiences of living with long COVID and of accessing healthcare services: a qualitative systematic review.}, journal = {BMJ open}, volume = {12}, number = {1}, pages = {e050979}, pmid = {35017239}, issn = {2044-6055}, mesh = {*COVID-19/complications ; Delivery of Health Care ; Female ; Health Services ; Humans ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To explore the experiences of people living with long COVID and how they perceive the healthcare services available to them.

DESIGN: Qualitative systematic review.

DATA SOURCES: Electronic literature searches of websites, bibliographic databases and discussion forums, including PubMed LitCovid, Proquest COVID, EPPI Centre living systematic map of evidence, medRxiv, bioRxiv, Medline, Psychinfo and Web of Science Core Collection were conducted to identify qualitative literature published in English up to 13 January 2021.

INCLUSION CRITERIA: Papers reporting qualitative or mixed-methods studies that focused on the experiences of long COVID and/or perceptions of accessing healthcare by people with long COVID. Title/abstract and full-text screening were conducted by two reviewers independently, with conflicts resolved by discussion or a third reviewer.

QUALITY APPRAISAL: Two reviewers independently appraised included studies using the qualitative CASP (Critical Appraisal Skills Programme) checklist. Conflicts were resolved by discussion or a third reviewer.

DATA EXTRACTION AND SYNTHESIS: Thematic synthesis, involving line-by-line reading, generation of concepts, descriptive and analytical themes, was conducted by the review team with regular discussion.

RESULTS: Five studies published in 2020 met the inclusion criteria, two international surveys and three qualitative studies from the UK. Sample sizes varied from 24 (interview study) to 3762 (survey). Participants were predominantly young white females recruited from social media or online support groups. Three analytical themes were generated: (1) symptoms and self-directed management of long COVID; (2) emotional aspects of living with long COVID and (3) healthcare experiences associated with long COVID.

CONCLUSIONS: People experience long COVID as a heterogeneous condition, with a variety of physical and emotional consequences. It appears that greater knowledge of long COVID is required by a number of stakeholders and that the design of emerging long COVID services or adaptation of existing services for long COVID patients should take account of patients' experiences in their design.}, } @article {pmid35017102, year = {2022}, author = {Fernández-de-Las-Peñas, C and Pellicer-Valero, OJ and Navarro-Pardo, E and Palacios-Ceña, D and Florencio, LL and Guijarro, C and Martín-Guerrero, JD}, title = {Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {116}, number = {}, pages = {241-244}, pmid = {35017102}, issn = {1878-3511}, mesh = {*COVID-19/complications ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: This multicenter study investigated clinical risk factors associated with the number of long-term symptoms after COVID.

METHODS: Clinical features, symptoms at hospital admission, hospitalization data, and the number of symptoms after COVID was systematically assessed for patients who recovered from COVID-19 in 4 hospitals in Madrid (Spain) from February 20 to May 31, 2020.

RESULTS: Overall, 1,969 patients (46.5% women, age: 61, SD: 16 years) were randomly assessed 8.4 months (SD 1.5) after hospital discharge. Female gender (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.57-2.10), number of morbidities (OR 1.182, 95% CI 1.08-1.29), number of symptoms at hospital admission (OR 1.309, 95% CI 1.15-1.49) and days at the hospital (OR 1.01, 95% CI 1.007-1.017) were associated (all, p <0.001) with more long-term symptoms after COVID. Further, vomiting (OR 1.78, 95% CI 1.26-2.52), throat pain (OR 1.36, 95% CI 1.02-1.81), diarrhea (OR 1.51, 95% CI 1.25-1.82), dyspnea (OR 1.20, 95% CI 1.01-1.41), or headache (OR 1.50, 95% CI 1.28-1.75) as symptoms at hospital admission were also associated (all, p <0.01) with a higher number of symptoms after COVID.

CONCLUSION: This multicenter study found that a higher number of symptoms at hospital admission were the most relevant risk factor for developing more symptoms after COVID, supporting the assumption that a higher symptom load at the acute phase is associated with a greater likelihood of long-term symptoms after COVID.}, } @article {pmid35014706, year = {2022}, author = {Gemignani, F}, title = {Small Fiber Neuropathy and SARS-CoV-2 Infection. Another piece in the long COVID puzzle?.}, journal = {Muscle & nerve}, volume = {65}, number = {4}, pages = {369-370}, doi = {10.1002/mus.27495}, pmid = {35014706}, issn = {1097-4598}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; *Small Fiber Neuropathy/diagnosis ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid35014543, year = {2022}, author = {Snowden, GT and Clement, ND and Zhang, S and Xue, Q and Simpson, AHRW}, title = {Orthopaedic long COVID - the unknown unknowns : are we facing a pandemic of avascular necrosis following COVID-19?.}, journal = {Bone & joint research}, volume = {11}, number = {1}, pages = {10-11}, pmid = {35014543}, issn = {2046-3758}, } @article {pmid35014002, year = {2022}, author = {Cristillo, V and Pilotto, A and Cotti Piccinelli, S and Bonzi, G and Canale, A and Gipponi, S and Bezzi, M and Leonardi, M and Padovani, A and , }, title = {Premorbid vulnerability and disease severity impact on Long-COVID cognitive impairment.}, journal = {Aging clinical and experimental research}, volume = {34}, number = {1}, pages = {257-260}, pmid = {35014002}, issn = {1720-8319}, mesh = {*COVID-19/complications ; *Cognitive Dysfunction/diagnosis ; Humans ; Longitudinal Studies ; SARS-CoV-2 ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Cognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.

AIMS: In this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).

METHODS: One hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).

RESULTS: Abnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1-2, 2020) (OR 1.27; 95% CI 1.05-1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1-2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53-14.63; p = 0.003) during the acute phase of the disease.

DISCUSSION: This longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.

CONCLUSIONS: These findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.}, } @article {pmid35012590, year = {2022}, author = {Principi, N and Esposito, S}, title = {Reasons in favour of universal vaccination campaign against COVID-19 in the pediatric population.}, journal = {Italian journal of pediatrics}, volume = {48}, number = {1}, pages = {4}, pmid = {35012590}, issn = {1824-7288}, mesh = {Adolescent ; Age Factors ; COVID-19/complications/epidemiology/*prevention & control ; *COVID-19 Vaccines ; Child ; Hospitalization ; Humans ; *Immunization Programs ; *Mandatory Programs ; Risk Assessment ; }, abstract = {BACKGROUND: Despite the growing evidence of the extreme efficacy of COVID-19 vaccines in adults and the elderly, the administration of the same prophylactic measures to pediatric subjects is debated by some parents and by a number of researchers. The aim of this manuscript is to explain the reasons for overcoming hesitancy towards COVID-19 vaccination in children and adolescents and to highlight the importance of universal COVID-19 vaccination in the pediatric population.

MAIN FINDINGS: Recent epidemiological data suggest that the risk that a child with COVID-19 is hospitalized or admitted to the pediatric intensive care unit is greater than initially thought. Children may also suffer from long COVID and school closure because of COVID-19 can cause relevant mental health problems in the pediatric population. Placebo-controlled, observer-blinded, clinical trials showed appropriate efficacy, safety and tolerability of authorized mRNA COVID-19 vaccines in children and adolescents 12-17 years old. Vaccination in children younger than 12 years of age will allow further benefits .

CONCLUSIONS: COVID-19 vaccine administration seems mandatory in all the children and adolescents because of COVID-19 related complications as well as the efficacy, safety and tolerability of COVID-19 vaccines in this population. Due to the recent approval of COVID-9 vaccines for children 5-10 years old, it is desirable that vaccine opponents can understand how important is the universal immunization against COVID-19 for the pediatric subjects.}, } @article {pmid35010786, year = {2022}, author = {Crankson, S and Pokhrel, S and Anokye, NK}, title = {Determinants of COVID-19-Related Length of Hospital Stays and Long COVID in Ghana: A Cross-Sectional Analysis.}, journal = {International journal of environmental research and public health}, volume = {19}, number = {1}, pages = {}, pmid = {35010786}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Ghana/epidemiology ; Humans ; Length of Stay ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: There is paucity of data on determinants of length of COVID-19 admissions and long COVID, an emerging long-term sequel of COVID-19, in Ghana. Therefore, this study identified these determinants and discussed their policy implications.

METHOD: Data of 2334 patients seen at the main COVID-19 treatment centre in Ghana were analysed in this study. Their characteristics, such as age, education level and comorbidities, were examined as explanatory variables. The dependent variables were length of COVID-19 hospitalisations and long COVID. Negative binomial and binary logistic regressions were fitted to investigate the determinants.

RESULT: The regression analyses showed that, on average, COVID-19 patients with hypertension and diabetes mellitus spent almost 2 days longer in hospital (p = 0.00, 95% CI = 1.42-2.33) and had 4 times the odds of long COVID (95% CI = 1.61-10.85, p = 0.003) compared to those with no comorbidities. In addition, the odds of long COVID decreased with increasing patient's education level (primary OR = 0.73, p = 0.02; secondary/vocational OR = 0.26, p = 0.02; tertiary education OR = 0.23, p = 0.12).

CONCLUSION: The presence of hypertension and diabetes mellitus determined both length of hospitalisation and long COVID among patients with COVID-19 in Ghana. COVID-19 prevention and management policies should therefore consider these factors.}, } @article {pmid35006516, year = {2022}, author = {Wagner, B and Steiner, M and Markovic, L and Crevenna, R}, title = {Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report.}, journal = {Wiener medizinische Wochenschrift (1946)}, volume = {172}, number = {9-10}, pages = {227-232}, pmid = {35006516}, issn = {1563-258X}, mesh = {*COVID-19/therapy ; *Electromagnetic Fields ; Fatigue/etiology/therapy ; Humans ; Quality of Life ; }, abstract = {BACKGROUND: Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication.

METHODS: Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures.

RESULTS: Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later.

CONCLUSION: The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.}, } @article {pmid35003784, year = {2021}, author = {Goel, N and Goyal, N and Kumar, R}, title = {Long COVID Mimicking Interstitial Lung Disease: A Case Series.}, journal = {Current health sciences journal}, volume = {47}, number = {3}, pages = {469-473}, pmid = {35003784}, issn = {2067-0656}, abstract = {Interstitial lung diseases (ILD) can occur due to various known or unknown causes. They usually present with dry cough and exertional dyspnea. On radiology usual findings are ground glass opacities (GGO's), reticular shadows, nodules etc. Some patients after acute COVID-19 (coronavirus disease 2019) suffer from persistent symptoms/manifestations. These have been called 'Long COVID'. Long COVID also has radiological features like GGO's, nodules and reticulations. Further, patients even without history of acute COVID-19, can also present with 'Long COVID'. In the present case series, we describe three such cases with no history of having suffered from COVID-19, presenting with ILD like features and diagnosed as Long COVID. We infer from these cases that 'Long COVID' can both clinically and radiologically mimic ILD's. Hence, emphasizing the fact that in the present COVID-19 pandemic situation, 'Long COVID should be a differential diagnosis to be considered while making a new diagnosis of ILD.}, } @article {pmid35000650, year = {2023}, author = {Fernández-de-Las-Peñas, C and Martín-Guerrero, JD and Cancela-Cilleruelo, I and Moro-López-Menchero, P and Rodríguez-Jiménez, J and Pellicer-Valero, OJ}, title = {Trajectory curves of post-COVID anxiety/depressive symptoms and sleep quality in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study.}, journal = {Psychological medicine}, volume = {53}, number = {9}, pages = {4298-4299}, pmid = {35000650}, issn = {1469-8978}, mesh = {Humans ; *COVID-19 ; Depression/epidemiology ; Post-Acute COVID-19 Syndrome ; Sleep Quality ; Anxiety/epidemiology ; Survivors ; }, } @article {pmid35000587, year = {2022}, author = {Gandjour, A}, title = {Benefits, risks, and cost-effectiveness of COVID-19 self-tests from a consumer's perspective.}, journal = {BMC health services research}, volume = {22}, number = {1}, pages = {47}, pmid = {35000587}, issn = {1472-6963}, mesh = {*COVID-19/diagnosis ; *Cost-Benefit Analysis ; Germany ; Humans ; Quality-Adjusted Life Years ; SARS-CoV-2 ; *Self-Testing ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The aim of this study is to quantify the health benefits, risks, and cost-effectiveness of COVID-19 self-tests from a consumer's perspective in Germany.

METHODS: The analysis is based on a modelling approach using secondary data. The clinical endpoints considered in this analysis are avoided SARS-CoV-2 infections and secondary severe clinical events (death, intensive care unit (ICU) admission, and long COVID syndrome). The study determines the number of self-tests that need to be conducted under a 7-day incidence of 75 per 100,000 population to prevent one infection or severe clinical event. Furthermore, the study calculates the cost of testing per avoided clinical event and quality-adjusted life year (QALY) gained from a consumer perspective.

RESULTS: Disregarding the rate of unreported COVID-19 cases, 4556 self-tests need to be conducted (over 12 years) in order to avoid one undesirable event (death, intensive care unit stay, or long COVID syndrome). Ninety percent of infections are not avoided among direct contacts but along the chain of infection. The costs per quality-adjusted life year gained from a consumer's perspective are €5870. This ratio is particularly sensitive to the 7-day incidence, effective reproduction number, and the age of contacts.

CONCLUSIONS: The benefits of self-testing in the general population at a 7-day incidence rate of 75 per 100,000 appear to be minor. Nevertheless, cost-effectiveness may still be acceptable in the presence of higher-risk contacts given the low costs of self-test kits in Germany.}, } @article {pmid35000003, year = {2022}, author = {Borch, L and Holm, M and Knudsen, M and Ellermann-Eriksen, S and Hagstroem, S}, title = {Long COVID symptoms and duration in SARS-CoV-2 positive children - a nationwide cohort study.}, journal = {European journal of pediatrics}, volume = {181}, number = {4}, pages = {1597-1607}, pmid = {35000003}, issn = {1432-1076}, mesh = {Adolescent ; Adult ; *COVID-19/complications ; Child ; Child, Preschool ; Cohort Studies ; Headache/etiology ; Humans ; Infant ; Infant, Newborn ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of 'long COVID' in children. A nationwide cohort study of 37,522 children aged 0-17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%). An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6-17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04-0.06), loss of smell RD 0.01 (CI 0.01-0.01), loss of taste RD 0.01 (CI 0.01-0.02) and muscle weakness RD 0.01 (CI 0.00-0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12-0.13), loss of taste RD 0.10 (CI 0.09-0.10), fatigue RD 0.05 (CI 0.05-0.06), respiratory problems RD 0.03 (CI 0.03-0.04), dizziness RD 0.02 (CI 0.02-0.03), muscle weakness RD 0.02 (CI 0.01-0.02) and chest pain RD 0.01 (CI 0.01-0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children 'long COVID' symptoms resolved within 1-5 months.

CONCLUSIONS: Long COVID in children is rare and mainly of short duration.

WHAT IS KNOWN: • There are increasing reports on 'long COVID' in adults. • Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group.

WHAT IS NEW: • 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks ('long COVID'), when compared to a control group. • The most common 'long COVID' symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems. • These 'long COVID' symptoms cannot be assigned to psychological sequelae of social restrictions. • Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not 'long COVID' symptoms. • In most cases 'long COVID' symptoms resolve within 1-5 months.}, } @article {pmid34997542, year = {2022}, author = {Stallmach, A and Kesselmeier, M and Bauer, M and Gramlich, J and Finke, K and Fischer, A and Fleischmann-Struzek, C and Heutelbeck, A and Katzer, K and Mutschke, S and Pletz, MW and Quickert, S and Reinhart, K and Stallmach, Z and Walter, M and Scherag, A and Reuken, PA}, title = {Comparison of fatigue, cognitive dysfunction and psychological disorders in post-COVID patients and patients after sepsis: is there a specific constellation?.}, journal = {Infection}, volume = {50}, number = {3}, pages = {661-669}, pmid = {34997542}, issn = {1439-0973}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *COVID-19/complications/epidemiology ; *Cognitive Dysfunction/epidemiology/etiology ; Disease Progression ; Fatigue/diagnosis/epidemiology/etiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; *Sepsis/complications/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis.

METHODS: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression.

RESULTS: Median age of the post-COVID patients was 51 years (range 17-86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients.

CONCLUSION: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection.}, } @article {pmid34994790, year = {2022}, author = {Donnelly, SC}, title = {The Long-COVID Syndrome: smoking and enhanced suicide risk.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {114}, number = {11}, pages = {765}, doi = {10.1093/qjmed/hcab300}, pmid = {34994790}, issn = {1460-2393}, mesh = {*COVID-19/complications ; Humans ; Risk Factors ; SARS-CoV-2 ; Smoking/adverse effects ; *Suicide ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34993037, year = {2021}, author = {Giri, A and Talwar, D and Acharya, S and Saggu, DK and Kumar, S}, title = {Atrial Tachycardia Masquerading As Inappropriate Sinus Tachycardia (IST) After COVID-19 Infection: A Matter of Concern?.}, journal = {Cureus}, volume = {13}, number = {12}, pages = {e20090}, pmid = {34993037}, issn = {2168-8184}, abstract = {COVID-19 Infection has wrecked havoc all over the world; the spectrum of this disease ranges from asymptomatic mild cases to severe cases such as acute respiratory distress syndrome (ARDS). Not only the acute infection but post COVID sequelae are also a cause of concern. Post-COVID states or Long COVID are the sequences of complications following the active infection. As post COVID sequelae are unpredictable it is absolutely the need of the hour to educate physicians and make them aware of all possibilities. We report one such case of a post COVID recovered young lady, who presented with drug-refractory recurrent palpitations. She was initially suspected to have inappropriate sinus tachycardia. But electrophysiological study confirmed the diagnosis of atrial tachycardia which was successfully ablated. The patient now has completed six months of follow-up and is off any medication.}, } @article {pmid34991703, year = {2022}, author = {Mera-Cordero, F and Bonet-Monne, S and Almeda-Ortega, J and García-Sangenís, A and Cunillera-Puèrtolas, O and Contreras-Martos, S and Alvarez-Muñoz, G and Monfà, R and Balanzo-Joué, M and Morros, R and Salvador-Gonzalez, B}, title = {Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol.}, journal = {Trials}, volume = {23}, number = {1}, pages = {19}, pmid = {34991703}, issn = {1745-6215}, mesh = {Acetates ; *COVID-19/complications ; Cyclopropanes ; Double-Blind Method ; Humans ; Oxygen Saturation ; Quality of Life ; Quinolines ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Sulfides ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect the globe. After 18 months of the SARS-CoV-2 emergence, clinicians have clearly defined a subgroup of patients with lasting, disabling symptoms. While big strides have been made in understanding the acute phase of SARS-CoV-2 infection, the pathophysiology of long COVID is still largely unknown, and evidence-based, effective treatments for this condition remain unavailable.

OBJECTIVES: To evaluate the efficacy of 10 mg oral montelukast every 24 h versus placebo in improving quality of life associated with mild to moderate respiratory symptoms in patients with long COVID as measured with the COPD Assessment Test (CAT) questionnaire. The secondary objectives will evaluate the effect of montelukast versus placebo on improving exercise capacity, COVID-19 symptoms (asthenia, headache, mental confusion or brain fog, ageusia, and anosmia), oxygen desaturation during exertion, functional status, and mortality.

METHODS AND ANALYSIS: Phase III, randomized, double-blind clinical trial. We will include 18- to 80-year-old patients with SARS-CoV-2 infection and mild to moderate respiratory symptoms lasting more than 4 weeks. Participants will be randomly allocated in a 1:1 ratio to the intervention (experimental treatment with 10 mg/day montelukast) or the control group (placebo group), during a 28-day treatment. Follow-up will finish 56 days after the start of treatment. The primary outcome will be health-related quality of life associated with respiratory symptoms according to the COPD Assessment Test 4 weeks after starting the treatment. The following are the secondary outcomes: (a) exercise capacity and oxygen saturation (1-min sit-to-stand test); (b) Post-COVID-19 Functional Status Scale; (c) other symptoms: asthenia, headache, mental confusion (brain fog), ageusia, and anosmia (Likert scale); (d) use of healthcare resources; (e) mortality; (f) sick leave duration in days; and (g) side effects of montelukast.

ETHICS AND DISSEMINATION: This study has been approved by the Clinical Research Ethics Committee of the IDIAPJGol (reference number 21/091-C). The trial results will be published in open access, peer-reviewed journals and explained in webinars to increase awareness and understanding about long COVID among primary health professionals.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04695704 . Registered on January 5, 2021. EudraCT number 2021-000605-24. Prospectively registered.}, } @article {pmid34986922, year = {2022}, author = {Heching, HJ and Goyal, A and Harvey, B and Malloy-Walton, L and Follansbee, C and Mcintosh, A and Forsha, D}, title = {Electrocardiographic changes in non-hospitalised children with COVID-19.}, journal = {Cardiology in the young}, volume = {32}, number = {12}, pages = {1910-1916}, doi = {10.1017/S1047951121005138}, pmid = {34986922}, issn = {1467-1107}, mesh = {Child ; Humans ; Male ; Female ; *COVID-19 ; Stroke Volume ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; Ventricular Function, Left ; Electrocardiography ; Arrhythmias, Cardiac/diagnosis ; *Myocarditis/diagnostic imaging ; }, abstract = {OBJECTIVES: Many children diagnosed with COVID-19 infections did not require hospitalisation. Our objective was to analyse electrocardiographic changes in children with asymptomatic, mild or moderate COVID-19 who did not require hospitalisation.

METHODS: All children are seen in a paediatric cardiology clinic who had asymptomatic, mild or moderate COVID-19 that did not require hospitalisation and had at least one electrocardiogram after their diagnosis were included in this retrospective analysis. Records were reviewed to determine COVID-19 disease severity and presence of Long COVID. Rhythm assessment, atrial enlargement, ventricular hypertrophy, PR/QRS/QT interval duration and ST-T wave abnormalities were analysed by a paediatric electrophysiologist. Clinically ordered echocardiograms were reviewed for signs of myopericarditis (left ventricular ejection fraction and pericardial effusion) on any subject with an electrocardiographic abnormality.

RESULTS: Of the 82 children meeting inclusion criteria (14.4 years, range 1-18 years, 57% male), 17 patients (21%) demonstrated electrocardiographic changes. Ten patients (12%) had electrocardiogram of borderline significance, which included isolated mild PR prolongation or mild repolarisation abnormalities. The other seven patients (9%) had concerning electrocardiographic findings consisting of more significant repolarisation abnormalities. None of the patients with an abnormal electrocardiogram revealed any echocardiographic abnormality. All abnormal electrocardiograms normalised over time except in two cases. Across the entire cohort, greater COVID-19 disease severity and long COVID were not associated with electrocardiographic abnormalities.

CONCLUSIONS: Electrocardiographic abnormalities are present in a minority of children with an asymptomatic, mild or moderate COVID-19 infection. Many of these changes resolved over time and no evidence of myopericarditis was present on echocardiography.}, } @article {pmid34982129, year = {2022}, author = {Slomski, A}, title = {Belief in Having Had COVID-19 Linked With Long COVID Symptoms.}, journal = {JAMA}, volume = {327}, number = {1}, pages = {26}, doi = {10.1001/jama.2021.23318}, pmid = {34982129}, issn = {1538-3598}, } @article {pmid34982039, year = {2022}, author = {Blanchard, M and Backhaus, L and Ming Azevedo, P and Hügle, T}, title = {An mHealth App for Fibromyalgia-like Post-COVID-19 Syndrome: Protocol for the Analysis of User Experience and Clinical Data.}, journal = {JMIR research protocols}, volume = {11}, number = {2}, pages = {e32193}, pmid = {34982039}, issn = {1929-0748}, abstract = {BACKGROUND: Post-COVID-19 syndrome, also referred as "long covid," describes persisting symptoms after SARS-CoV-2 infection, including myalgia, fatigue, respiratory, or neurological symptoms. Objective symptoms are often lacking, thus resembling a fibromyalgia-like syndrome. Digital therapeutics have shown efficiency in similar chronic disorders such as fibromyalgia, offering specific disease monitoring and interventions such as cognitive behavioral therapy or physical and respiratory exercise guidance.

OBJECTIVE: This protocol aims to study the requirements and features of a new mobile health (mHealth) app among patients with fibromyalgia-like post-COVID-19 syndrome in a clinical trial.

METHODS: We created a web application prototype for the post-COVID-19 syndrome called "POCOS," as a web-based rehabilitation tool aiming to improve clinical outcomes. Patients without organ damage or ongoing inflammation will be included in the study. App use will be assessed through user experience questionnaires, focus groups, and clinical data analysis. Subsequently, we will analyze cross-sectional and longitudinal clinical data.

RESULTS: The developed mHealth app consists of a clinically adapted app interface with a simplified patient-reported outcome assessment, monitoring of medical interventions, and disease activity as well as web-based instructions for specific physical and respiratory exercises, stress reduction, and lifestyle instructions. The enrollment of participants is expected to be carried out in November 2021.

CONCLUSIONS: User experience plays an important role in digital therapeutics and needs to be clinically tested to allow further improvement. We here describe this process for a new app for the treatment of the fibromyalgia-like post-COVID-19 syndrome and discuss the relevance of the potential outcomes such as natural disease course and disease phenotypes.

PRR1-10.2196/32193.}, } @article {pmid34973396, year = {2022}, author = {Ceban, F and Ling, S and Lui, LMW and Lee, Y and Gill, H and Teopiz, KM and Rodrigues, NB and Subramaniapillai, M and Di Vincenzo, JD and Cao, B and Lin, K and Mansur, RB and Ho, RC and Rosenblat, JD and Miskowiak, KW and Vinberg, M and Maletic, V and McIntyre, RS}, title = {Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.}, journal = {Brain, behavior, and immunity}, volume = {101}, number = {}, pages = {93-135}, pmid = {34973396}, issn = {1090-2139}, mesh = {*COVID-19/complications ; COVID-19 Testing ; *Cognitive Dysfunction ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.

OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.

DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.

STUDY SELECTION: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.

Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.

MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.

RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I[2] = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I[2] = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.

CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.

STUDY REGISTRATION: PROSPERO (CRD42021256965).}, } @article {pmid34972801, year = {2022}, author = {Hussain, FA}, title = {Facilitating care: a biopsychosocial perspective on long COVID.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {714}, pages = {30-31}, doi = {10.3399/bjgp22X718181}, pmid = {34972801}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34972793, year = {2022}, author = {Kavi, L}, title = {Postural tachycardia syndrome and long COVID: an update.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {72}, number = {714}, pages = {8-9}, pmid = {34972793}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34970914, year = {2022}, author = {Weber, B and Siddiqi, H and Zhou, G and Vieira, J and Kim, A and Rutherford, H and Mitre, X and Feeley, M and Oganezova, K and Varshney, AS and Bhatt, AS and Nauffal, V and Atri, DS and Blankstein, R and Karlson, EW and Di Carli, M and Baden, LR and Bhatt, DL and Woolley, AE}, title = {Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes.}, journal = {Journal of the American Heart Association}, volume = {11}, number = {1}, pages = {e022010}, pmid = {34970914}, issn = {2047-9980}, support = {K23 HL159276/HL/NHLBI NIH HHS/United States ; T32 HL094301/HL/NHLBI NIH HHS/United States ; }, mesh = {*COVID-19/complications/therapy ; *Heart Injuries/epidemiology ; Hospitalization ; Humans ; Prospective Studies ; Treatment Outcome ; Troponin T/blood ; }, abstract = {Background Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.}, } @article {pmid34968019, year = {2021}, author = {Samartsev, IN and Zhivolupov, SA and Butakova, JS and Parshin, MS}, title = {[The open observational study of aceclofenac and vinpocetine effectiveness and tolerability in treatment of patients with chronic cerebrovascular disease after COVID-19 (AQUA study)].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {121}, number = {11}, pages = {s1-s8}, doi = {10.17116/jnevro2021121111s1}, pmid = {34968019}, issn = {1997-7298}, mesh = {Aged ; *COVID-19/complications ; *Cerebrovascular Disorders/drug therapy/epidemiology ; Diclofenac/analogs & derivatives/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Vinca Alkaloids/*therapeutic use ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {OBJECTIVE: To estimate the frequency of long-COVID in patients with chronic cerebrovascular disease, to identify the risk factors for the development of this condition and to analyze effectiveness and tolerability of Vinpocetine and Aertal in treatment of this disease.

MATERIAL AND METHODS: The study included 97 patients (64.5±5.2 years), among which 42 were diagnosed with long-COVID. The effectiveness of treatment was analyzed with NRS-P, Post-COVID-19 Functional Status (PCFS), Global Rating of Change Scale (GROC).

RESULTS: Predictors of long-COVID was female gender (p=0.022), severe COVID-19 (p=0.035), comorbidities: cardiovascular diseases (p=0.032), endocrinopathies (p=0.041), affective disorders (p=0.021). Significant changes in the functional status of patients were recorded after 20 days of treatment (PCFS), in pain after 10 days (NRS-P). The most pronounced clinical effect (PCFS) was obtained after 1 mth of therapy with vinpocetine and 20 days with aceclofenac (NRS-P). After 30 days 25/59.5% of patients noted a «pronounced» improvement in their own well-being (GROC) without the development of significant side effects.

CONCLUSIONS: 43.3% of patients with chronic cerebrovascular disease and certain predictors develop long-COVID. Aceclofenac and vinpocetine are effective in relieving a number of symptoms of long-COVID, which requires further study.}, } @article {pmid34964184, year = {2022}, author = {Merikanto, I and Dauvilliers, Y and Chung, F and Holzinger, B and De Gennaro, L and Wing, YK and Korman, M and Partinen, M and , }, title = {Disturbances in sleep, circadian rhythms and daytime functioning in relation to coronavirus infection and Long-COVID - A multinational ICOSS study.}, journal = {Journal of sleep research}, volume = {31}, number = {4}, pages = {e13542}, doi = {10.1111/jsr.13542}, pmid = {34964184}, issn = {1365-2869}, mesh = {*COVID-19/complications ; Circadian Rhythm ; Humans ; SARS-CoV-2 ; Sleep ; Post-Acute COVID-19 Syndrome ; }, abstract = {This protocol paper describes the second survey produced by the International Covid Sleep Study (ICOSS) group with the aim to examine the associations between SARS-CoV-2 infection and sleep, sleepiness, and circadian problems as potential predisposing factors for more severe COVID-19 disease profile and for development of Long-COVID in the general population. The survey consists of 47 questions on sleep, daytime sleepiness, circadian rhythm, health, mental wellbeing, life habits, and socioeconomic situation before and during the pandemic, and conditional questions to those reporting having had coronavirus infection, being vaccinated, or suffering from particular sleep symptoms or sleep disorders. Surveys will be administered online between May and November 2021 in Austria, Brazil, Bulgaria, Canada, China, Croatia, Finland, France, Germany, Israel, Italy, Japan, Norway, Portugal, Sweden and USA. Data collected by the survey will give valuable information on the open questions regarding COVID-19 disease risk factors, symptomatology and evolution of Long-COVID, and on other long-term consequences related to the pandemic.}, } @article {pmid34964039, year = {2022}, author = {Gavriilaki, E and Maiques-Diaz, A}, title = {"Long COVID-19" of Researchers: What to Do Next?.}, journal = {HemaSphere}, volume = {6}, number = {1}, pages = {e673}, pmid = {34964039}, issn = {2572-9241}, } @article {pmid34960661, year = {2021}, author = {St Clair, LA and Brehm, AL and Cagle, S and Dunham, T and Faris, J and Gendler, P and Graham, ME and Quackenbush, SL and Rovnak, J and Perera, R}, title = {The 21st Annual Meeting of the Rocky Mountain Virology Association.}, journal = {Viruses}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/v13122392}, pmid = {34960661}, issn = {1999-4915}, support = {R13 AI164787/AI/NIAID NIH HHS/United States ; R13 AI164787-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Host-Pathogen Interactions ; Humans ; Pandemics/prevention & control ; Prion Diseases/diagnosis/prevention & control ; Prions/immunology/isolation & purification/pathogenicity ; Vaccines ; *Virology/organization & administration ; Virus Diseases/diagnosis/epidemiology/prevention & control/virology ; Viruses/classification/immunology/isolation & purification/pathogenicity ; }, abstract = {Nestled within the Rocky Mountain National Forest, 114 scientists and students gathered at Colorado State University's Mountain Campus for this year's 21st annual Rocky Mountain National Virology Association meeting. This 3-day retreat consisted of 31 talks and 30 poster presentations discussing advances in research pertaining to viral and prion diseases. The keynote address provided a timely discussion on zoonotic coronaviruses, lessons learned, and the path forward towards predicting, preparing, and preventing future viral disease outbreaks. Other invited speakers discussed advances in SARS-CoV-2 surveillance, molecular interactions involved in flavivirus genome assembly, evaluation of ethnomedicines for their efficacy against infectious diseases, multi-omic analyses to define risk factors associated with long COVID, the role that interferon lambda plays in control of viral pathogenesis, cell-fusion-dependent pathogenesis of varicella zoster virus, and advances in the development of a vaccine platform against prion diseases. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations.}, } @article {pmid34951953, year = {2022}, author = {Soriano, JB and Murthy, S and Marshall, JC and Relan, P and Diaz, JV and , }, title = {A clinical case definition of post-COVID-19 condition by a Delphi consensus.}, journal = {The Lancet. Infectious diseases}, volume = {22}, number = {4}, pages = {e102-e107}, pmid = {34951953}, issn = {1474-4457}, support = {001/WHO_/World Health Organization/International ; }, mesh = {Adult ; *COVID-19/complications ; Child ; Consensus ; Delphi Technique ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.}, } @article {pmid34951387, year = {2022}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Ptacek, R and Wang, F and Esch, T and Bilfinger, TV and Raboch, J and Kream, RM}, title = {Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19.}, journal = {Current neuropharmacology}, volume = {20}, number = {6}, pages = {1229-1240}, pmid = {34951387}, issn = {1875-6190}, mesh = {*COVID-19/complications ; Central Nervous System ; Disease Progression ; Humans ; *Neurodegenerative Diseases ; Pandemics ; SARS-CoV-2 ; }, abstract = {The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China, in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long-term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as "brain fog" which comprises difficulty concentrating, forgetfulness, confusion, depression, and fatigue. Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad-based working models have focused on mitochondrial dysregulation, leading to systemic reductions of metabolic activity and cellular bioenergetics within the CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults, leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens. By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.}, } @article {pmid34948983, year = {2021}, author = {Cascella, M and Miceli, L and Cutugno, F and Di Lorenzo, G and Morabito, A and Oriente, A and Massazza, G and Magni, A and Marinangeli, F and Cuomo, A and On Behalf Of The Delphi Panel, }, title = {A Delphi Consensus Approach for the Management of Chronic Pain during and after the COVID-19 Era.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948983}, issn = {1660-4601}, mesh = {*COVID-19/complications ; *Chronic Pain/diagnosis/therapy ; Consensus ; Delphi Technique ; Humans ; *Pain Management ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Due to a lack of published evidence on the topic, a modified Delphi approach was used to develop recommendations useful for chronic pain management during and after the COVID-19 pandemic. Focusing on the available literature and personal clinical expertise, an Italian board of nine professionals from different disciplines identified four main topics: prevention of chronic pain, treatment of chronic pain, consequences of inadequate treatment, and perspectives. They elaborated a semi-structured questionnaire. A multidisciplinary panel of experts in the field of pain management was requested to comment on the statements. Based on the answers provided, a structured questionnaire was prepared (Round 1). It included 21 statements divided into three categories (organizational issues; diagnosis and therapies; telemedicine and future perspectives). A five-point Likert scale was adopted. The threshold for consensus was set at a minimum of 70% of the number of respondents (level of agreement ≥ 4, Agree or Strongly Agree). A final questionnaire with rephrasing of the statements that did not reach the consensus threshold was elaborated (Round 2). A total of 29 clinicians were included in the panel. Twenty clinicians (69%) responded in both the first and second round. After two rounds, consensus (≥70%) was achieved in 20 out of 21 statements. The lack of consensus was recorded for the statement regarding the management of post-COVID pain (55%; Median 4; IQR 2.3). Another statement on telemedicine reached the threshold in the first round (70%), but the value was not confirmed in Round 2 (65%; Median 4; IQR 2). Most of the proposed items reached consensus, suggesting the need to make organizational changes, the structuring of careful diagnostic and therapeutic pathways, and the application of new technologies in pain medicine. Long-COVID-19 care is an issue that needs further research. Remote assistance for chronic pain must be regulated.}, } @article {pmid34948858, year = {2021}, author = {Lira, FS and Pereira, T and Guerra Minuzzi, L and Figueiredo, C and Olean-Oliveira, T and Figueira Freire, APC and Coelho-E-Silva, MJ and Caseiro, A and Thomatieli-Santos, RV and Dos Santos, VR and Gobbo, LA and Seelaender, M and Krüger, K and Pinho, RA and Rosa-Neto, JC and de Alencar Silva, BS}, title = {Modulatory Effects of Physical Activity Levels on Immune Responses and General Clinical Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections-A Protocol for an Observational Prospective Follow-Up Investigation: Fit-COVID-19 Study.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948858}, issn = {1660-4601}, mesh = {Adult ; *COVID-19 ; Exercise ; Follow-Up Studies ; Humans ; Immunity ; Leukocytes, Mononuclear ; Observational Studies as Topic ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {Background: This proposal aims to explain some of the gaps in scientific knowledge on the natural history of coronavirus disease (COVID-19), with a specific focus on immune, inflammatory, and metabolic markers, in parallel with temporal assessment of clinical and mental health in patients with COVID-19. The study will explore the temporal modulatory effects of physical activity and body composition on individual trajectories. This approach will provide a better understanding of the survival mechanisms provided by the immunomodulatory role of physical fitness. Methods: We will conduct a prospective observational cohort study including adult patients previously infected with the SARS-CoV-2 virus who have expressed a mild to moderate COVID-19 infection. Procedures will be conducted for all participants at baseline, six weeks after vaccination, and again at 12 months. At each visit, a venous blood sample will be collected for immune phenotypic characterization and biochemistry assays (inflammatory and metabolic parameters). Also, body composition, physical activity level, cardiovascular and pulmonary function, peripheral and respiratory muscle strength, functional exercise capacity, and mental health will be evaluated. Using the baseline information, participants will be grouped based on physical activity levels (sedentary versus active), body composition (normal weight versus overweight or obese), and SARS-CoV-2 status (positive versus negative). A sub-study will provide mechanistic evidence using an in-vitro assay based on well-trained individuals and age-matched sedentary controls who are negative for SARS-CoV-2 infection. Whole blood will be stimulated using recombinant human coronavirus to determine the cytokine profile. Peripheral blood mononuclear cells (PBMCs) from healthy well-trained participants will be collected and treated with homologous serum (from the main study; samples collected before and after the vaccine) and recombinant coronavirus (inactive virus). The metabolism of PBMCs will be analyzed using Respirometry (Seahorse). Data will be analyzed using multilevel repeated-measures ANOVA. Conclusions: The data generated will help us answer three main questions: (1) Does the innate immune system of physically active individuals respond better to viral infections compared with that of sedentary people? (2) which functional and metabolic mechanisms explain the differences in responses in participants with different physical fitness levels? and (3) do these mechanisms have long-term positive modulatory effects on mental and cardiovascular health? Trial registration number: Brazilian Registry of Clinical Trials: RBR-5dqvkv3. Registered on 21 September 2021.}, } @article {pmid34948798, year = {2021}, author = {Fowler-Davis, S and Young, R and Maden-Wilkinson, T and Hameed, W and Dracas, E and Hurrell, E and Bahl, R and Kilcourse, E and Robinson, R and Copeland, R}, title = {Assessing the Acceptability of a Co-Produced Long COVID Intervention in an Underserved Community in the UK.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {24}, pages = {}, pmid = {34948798}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Female ; Humans ; Male ; *Medically Underserved Area ; Pandemics ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long COVID is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long COVID living in communities recognised as more deprived.

METHODS: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual 'clinic' was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual's participation and their completion of the intervention.

RESULTS: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long COVID difficulties.

CONCLUSIONS: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long COVID.}, } @article {pmid34946430, year = {2021}, author = {Muratori Holanda, T and Alberico, C and Rios-Colon, L and Arthur, E and Kumar, D}, title = {Trends in COVID-19 Health Disparities in North Carolina: Preparing the Field for Long-Haul Patients.}, journal = {Healthcare (Basel, Switzerland)}, volume = {9}, number = {12}, pages = {}, pmid = {34946430}, issn = {2227-9032}, support = {U24 MD015970/MD/NIMHD NIH HHS/United States ; U54MD012392/MD/NIMHD NIH HHS/United States ; R01MD012767/MD/NIMHD NIH HHS/United States ; }, abstract = {Long-term coronavirus disease 2019 (long-COVID) refers to persistent symptoms of SARS-CoV-2 (COVID-19) lingering beyond four weeks of initial infection. Approximately 30% of COVID-19 survivors develop prolonged symptoms. Communities of color are disproportionately affected by comorbidities, increasing the risk of severe COVID-19 and potentially leading to long-COVID. This study aims to identify trends in health disparities related to COVID-19 cases, which can help unveil potential populations at risk for long-COVID. All North Carolina (NC) counties (n = 100) were selected as a case study. Cases and vaccinations per 1000 population were calculated based on the NC Department of Health and Human Services COVID-19 dashboard with reports current as of 8 October 2021, which were stratified by age groups and race/ethnicity. Then, NC COVID-19 cases were correlated to median household income, poverty, population density, and social vulnerability index themes. We observed a negative correlation between cases (p < 0.05) and deaths (p < 0.01) with both income and vaccination status. Moreover, there was a significant positive association between vaccination status and median household income (p < 0.01). Our results highlight the prevailing trend between exacerbated COVID-19 infection and low-income/under-resourced communities. Consequently, efforts and resources should be channeled to these communities to effectively monitor, diagnose, and treat against COVID-19 and potentially prevent an overwhelming number of long-COVID cases.}, } @article {pmid34945213, year = {2021}, author = {Jennings, G and Monaghan, A and Xue, F and Mockler, D and Romero-Ortuño, R}, title = {A Systematic Review of Persistent Symptoms and Residual Abnormal Functioning following Acute COVID-19: Ongoing Symptomatic Phase vs. Post-COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945213}, issn = {2077-0383}, support = {SFI COVID-19 Programme - 20/COV/8493/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {OBJECTIVE: To compare the two phases of long COVID, namely ongoing symptomatic COVID-19 (OSC; signs and symptoms from 4 to 12 weeks from initial infection) and post-COVID-19 syndrome (PCS; signs and symptoms beyond 12 weeks) with respect to symptomatology, abnormal functioning, psychological burden, and quality of life.

DESIGN: Systematic review.

DATA SOURCES: Electronic search of EMBASE, MEDLINE, ProQuest Coronavirus Research Database, LitCOVID, and Google Scholar between January and April 2021, and manual search for relevant citations from review articles. Eligibility Criteria: Cross-sectional studies, cohort studies, randomised control trials, and case-control studies with participant data concerning long COVID symptomatology or abnormal functioning.

DATA EXTRACTION: Studies were screened and assessed for risk of bias by two independent reviewers, with conflicts resolved with a third reviewer. The AXIS tool was utilised to appraise the quality of the evidence. Data were extracted and collated using a data extraction tool in Microsoft Excel.

RESULTS: Of the 1145 studies screened, 39 were included, all describing adult cohorts with long COVID and sample sizes ranging from 32 to 1733. Studies included data pertaining to symptomatology, pulmonary functioning, chest imaging, cognitive functioning, psychological disorder, and/or quality of life. Fatigue presented as the most prevalent symptom during both OSC and PCS at 43% and 44%, respectively. Sleep disorder (36%; 33%), dyspnoea (31%; 40%), and cough (26%; 22%) followed in prevalence. Abnormal spirometry (FEV1 < 80% predicted) was observed in 15% and 11%, and abnormal chest imaging was observed in 34% and 28%, respectively. Cognitive impairments were also evident (20%; 15%), as well as anxiety (28%; 34%) and depression (25%; 32%). Decreased quality of life was reported by 40% in those with OSC and 57% with PCS.

CONCLUSIONS: The prevalence of OSC and PCS were highly variable. Reported symptoms covered a wide range of body systems, with a general overlap in frequencies between the two phases. However, abnormalities in lung function and imaging seemed to be more common in OSC, whilst anxiety, depression, and poor quality of life seemed more frequent in PCS. In general, the quality of the evidence was moderate and further research is needed to understand longitudinal symptomatology trajectories in long COVID. Systematic Review Registration: Registered with PROSPERO with ID #CRD42021247846.}, } @article {pmid34945155, year = {2021}, author = {Bellavia, S and Scala, I and Luigetti, M and Brunetti, V and Gabrielli, M and Zileri Dal Verme, L and Servidei, S and Calabresi, P and Frisullo, G and Della Marca, G}, title = {Instrumental Evaluation of COVID-19 Related Dysautonomia in Non-Critically-Ill Patients: An Observational, Cross-Sectional Study.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945155}, issn = {2077-0383}, abstract = {Coronavirus disease-19 (COVID-19) is a predominantly respiratory syndrome. Growing reports about a SARS-CoV-2 neurological involvement, including autonomic dysfunction (AD), have been reported, mostly in critically-ill patients, or in the long-COVID syndrome. In this observational, cross-sectional study, we investigated the prevalence of AD in 20 non-critically-ill COVID-19 patients (COVID+ group) in the acute phase of the disease through a composite instrumental evaluation consisting of Sudoscan, automated pupillometry, heart rate variability (HRV), and pulse transit time (PTT). All the parameters were compared to a control group of 20 healthy volunteers (COVID- group). COVID+ group presented higher values of pupillary dilatation velocities, and baseline pupil diameter than COVID- subjects. Moreover, COVID+ patients presented a higher incidence of feet sudomotor dysfunction than COVID- group. No significant differences emerged in HRV and PTT parameters between groups. In this study we observed the occurrence of autonomic dysfunction in the early stage of the disease.}, } @article {pmid34945095, year = {2021}, author = {Fernández-Lázaro, D and Sánchez-Serrano, N and Mielgo-Ayuso, J and García-Hernández, JL and González-Bernal, JJ and Seco-Calvo, J}, title = {Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, pmid = {34945095}, issn = {2077-0383}, support = {07.04.467804.74011.0//Instituto de Salud Carlos III/ ; ° 07.04.467804.74011.0//Consejería de Educación Junta of Castilla-Leon/ ; }, abstract = {Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as "Long COVID" (LC). Patients with LC may develop multi-organ symptom complex that remains 4-12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus-host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC.}, } @article {pmid34944747, year = {2021}, author = {Colarusso, C and Maglio, A and Terlizzi, M and Vitale, C and Molino, A and Pinto, A and Vatrella, A and Sorrentino, R}, title = {Post-COVID-19 Patients Who Develop Lung Fibrotic-like Changes Have Lower Circulating Levels of IFN-β but Higher Levels of IL-1α and TGF-β.}, journal = {Biomedicines}, volume = {9}, number = {12}, pages = {}, pmid = {34944747}, issn = {2227-9059}, abstract = {PURPOSE: SARS-CoV-2 infection induces in some patients a condition called long-COVID-19, herein post-COVID-19 (PC), which persists for longer than the negative oral-pharyngeal swab. One of the complications of PC is pulmonary fibrosis. The purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis.

PATIENTS AND METHODS: We analyzed blood samples of healthy, anti-SARS-CoV-2 vaccinated (VAX) subjects and PC patients who were stratified according to the severity of the disease and chest computed tomography (CT) scan data.

RESULTS: The inflammatory C reactive protein (CRP), complement complex C5b-9, LDH, but not IL-6, were higher in PC patients, independent of the severity of the disease and lung fibrotic areas. Interestingly, PC patients with ground-glass opacities (as revealed by chest CT scan) were characterized by higher plasma levels of IL-1α, CXCL-10, TGF-β, but not of IFN-β, compared to healthy and VAX subjects. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-β, but higher IL-1α and TGF-β.

CONCLUSIONS: We found that higher IL-1α and TGF-β and lower plasma levels of IFN-β could predict an increased relative risk (RR = 2.8) of lung fibrosis-like changes in PC patients.}, } @article {pmid34943875, year = {2021}, author = {Lynch, SM and Guo, G and Gibson, DS and Bjourson, AJ and Rai, TS}, title = {Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease.}, journal = {Cells}, volume = {10}, number = {12}, pages = {}, pmid = {34943875}, issn = {2073-4409}, support = {COM/5618/20//Public Health Agency/ ; }, mesh = {Aging/*pathology ; Animals ; Biomarkers/metabolism ; COVID-19/*pathology ; Cellular Senescence ; Humans ; SARS-CoV-2/*physiology ; Translational Research, Biomedical ; }, abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or "sendotypes"), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.}, } @article {pmid34942461, year = {2022}, author = {May, BC and Gallivan, KH}, title = {Levocetirizine and montelukast in the COVID-19 treatment paradigm.}, journal = {International immunopharmacology}, volume = {103}, number = {}, pages = {108412}, pmid = {34942461}, issn = {1878-1705}, mesh = {Acetates/*therapeutic use ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cetirizine/*therapeutic use ; Child ; Child, Preschool ; Cyclopropanes/*therapeutic use ; Female ; Histamine H1 Antagonists, Non-Sedating/*therapeutic use ; Humans ; Leukotriene Antagonists/*therapeutic use ; Male ; Middle Aged ; Quinolines/*therapeutic use ; Retrospective Studies ; SARS-CoV-2/*drug effects ; Sulfides/*therapeutic use ; Treatment Outcome ; Young Adult ; *COVID-19 Drug Treatment ; }, abstract = {Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.}, } @article {pmid34940980, year = {2021}, author = {Danieli, MG and Piga, MA and Paladini, A and Longhi, E and Mezzanotte, C and Moroncini, G and Shoenfeld, Y}, title = {Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease.}, journal = {Scandinavian journal of immunology}, volume = {94}, number = {5}, pages = {e13101}, pmid = {34940980}, issn = {1365-3083}, mesh = {Adult ; Antiviral Agents/*therapeutic use ; Autoimmune Diseases/etiology/immunology/*prevention & control ; COVID-19/*complications/etiology/immunology/prevention & control ; COVID-19 Vaccines/adverse effects/*immunology ; Chemotherapy, Adjuvant ; Critical Illness ; Humans ; Immunoglobulins, Intravenous/*therapeutic use ; Italy ; Length of Stay ; Respiration, Artificial ; SARS-CoV-2/*physiology ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called 'cytokines storm' is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg). We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome. The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies' limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.}, } @article {pmid34940941, year = {2022}, author = {Tryfou, ES and Kostakou, PM and Chasikidis, CG and Kostopoulos, VS and Serafetinidis, II and Ferdianaki, EK and Mihas, C and Olympios, CD and Kouris, NT}, title = {Biventricular myocardial function in Covid-19 recovered patients assessed by speckle tracking echocardiography: a prospective cohort echocardiography study.}, journal = {The international journal of cardiovascular imaging}, volume = {38}, number = {5}, pages = {995-1003}, pmid = {34940941}, issn = {1875-8312}, abstract = {Although severe acute respiratory syndrome coronavirus 2 causes respiratory disease, it may also lead to cardiovascular involvement with unknown long-term consequences. The aim of our study was to evaluate prospectively cardiac involvement in patients after the recovery from Covid-19, using two-dimensional speckle tracking echocardiography. 100 Covid-19 recovered patients with preserved left ventricular ejection fraction, were included, divided based upon clinical manifestation into two groups, those who were treated ambulant and those who were hospitalized. All patients underwent echocardiographic evaluation after their recovery. Although overall LV systolic function expressed by EF was normal, left ventricular global longitudinal strain (LVGLS) was significantly lower in Covid-19 recovered patients (33.28 ± 9.4 days after diagnosis) compared to controls (- 18.47 ± - 2.4 vs. - 21.07 ± - 1.76% respectively, p < 0.0001). Εspecially the lateral wall longitudinal strain (LATLS) and posterior wall longitudinal strain (POSTLS) were significantly reduced in all patients compared to controls (- 17.77 ± - 3.48 vs. - 20.97 ± - 2.86%, p < 0.0001 and - 19.52 ± - 5.3 vs. - 22.23 ± - 2.65%, p = 0.01). right ventricular global longitudinal strain (RVGLS) was significantly diminished only in the hospitalized group of Covid-19 recovered patients, compared to controls (- 18.17 ± - 3.32 vs. - 26.03 ± - 4.55% respectively, p < 0.0001). LVGLS is affected in almost all individuals after Covid-19 infection independently of the infection severity, with LATLS being the most sensitive marker of LV impairment and with POSTLS to follow. RV shows impaired GLS in severely ill patients highlighting RVGLS as a helpful tool of prognosis. Recovered patients from Covid-19 infection have to be monitored for a long time, since the term "long Covid disease" might also include the cardiac function.}, } @article {pmid34939506, year = {2021}, author = {Harenwall, S and Heywood-Everett, S and Henderson, R and Godsell, S and Jordan, S and Moore, A and Philpot, U and Shepherd, K and Smith, J and Bland, AR}, title = {Post-Covid-19 Syndrome: Improvements in Health-Related Quality of Life Following Psychology-Led Interdisciplinary Virtual Rehabilitation.}, journal = {Journal of primary care & community health}, volume = {12}, number = {}, pages = {21501319211067674}, pmid = {34939506}, issn = {2150-1327}, mesh = {*COVID-19/complications ; Humans ; Quality of Life ; SARS-CoV-2 ; *Telerehabilitation ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is increasingly recognized as having significant long-term impact on physical and mental health. The Primary Care Wellbeing Service (PCWBS) in Bradford District Care NHS Foundation Trust (BDCFT) is a psychology-led specialist interdisciplinary team of health professionals specializing in persistent physical symptoms (PPS) and Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) with an emphasis on holistic integrated care. The PCWBS quickly recognized the risk of the long-term effects of COVID-19, particularly for social, health and care staff, and developed a 7-week virtual rehabilitation course which was piloted in October 2020. The "Recovering from COVID" course takes a whole system, biopsychosocial approach to understanding COVID-19 and post-viral fatigue (PVF) and is delivered by an interdisciplinary team consisting of a clinical psychologist, physiotherapist, occupational therapist, dietitian, speech and language therapist, assistant psychologist, and a personal support navigator with support from a team administrator. The course focuses on understanding PVF, sleep optimization, nutrition, swallowing, activity management, energy conservation, stress management, breathing optimization, managing setbacks, and signposting to appropriate resources and services. Since the pilot, PCWBS has delivered 7 courses to support over 200 people suffering from post-COVID-19 syndrome. One hundred and forty-nine individuals that enrolled on the "Recovering from COVID" course completed the EQ-5D-5L to assess Health-related quality of life (HRQoL) across 5 dimensions, including problems with mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Subsequently, 76 individuals completed these measures at the end of the rehabilitation course showing that patient ratings were significantly improved. In response to the NIHR recommendation for rapid evaluation of different service models for supporting people with post-COVID-19 syndrome, this data offers hope that rehabilitation is effective in reversing some of the problems faced by people living with the long-term effects of COVID-19.}, } @article {pmid34935514, year = {2022}, author = {Tyack, C and Unadkat, S and Voisnyte, J}, title = {Adolescent sleep - lessons from COVID-19.}, journal = {Clinical child psychology and psychiatry}, volume = {27}, number = {1}, pages = {6-17}, pmid = {34935514}, issn = {1461-7021}, mesh = {Adolescent ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Sleep ; Post-Acute COVID-19 Syndrome ; }, abstract = {Sleep in adolescents was significantly impacted by the COVID-19 pandemic. We present a commentary on a range of articles exploring COVID-19's impact on sleep in teenagers, exploring the variety of effects internationally, interactions with sleep biology and the environment, mental health, online learning and Long COVID. We conclude with vicious and virtuous flowers suggesting ways to mitigate the impacts of COVID-19 on adolescent sleep.}, } @article {pmid34934117, year = {2021}, author = {Williams, TL and Strachan, G and Macrae, RGC and Kuc, RE and Nyimanu, D and Paterson, AL and Sinha, S and Maguire, JJ and Davenport, AP}, title = {Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {24336}, pmid = {34934117}, issn = {2045-2322}, support = {MC_PC_17230/MRC_/Medical Research Council/United Kingdom ; FS/13/29/30024/BHF_/British Heart Foundation/United Kingdom ; 208363/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; 203814/Z/16/A/WT_/Wellcome Trust/United Kingdom ; SP/15/7/31561/BHF_/British Heart Foundation/United Kingdom ; FS/17/61/33473/BHF_/British Heart Foundation/United Kingdom ; WT107715/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; FS/18/46/33663/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Angiotensin-Converting Enzyme 2/chemistry/genetics/*metabolism ; Bile Ducts/metabolism/virology ; Binding Sites ; COVID-19/pathology/virology ; Humans ; Lung/metabolism/virology ; Microscopy, Fluorescence, Multiphoton ; Protein Binding ; Protein Isoforms/chemistry/genetics/metabolism ; Receptors, Virus/chemistry/metabolism ; SARS-CoV-2/isolation & purification/*physiology ; Spike Glycoprotein, Coronavirus/chemistry/*metabolism ; Virus Internalization ; }, abstract = {ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent 'Long COVID'. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.}, } @article {pmid34933829, year = {2022}, author = {Sansone, A and Mollaioli, D and Limoncin, E and Ciocca, G and Bắc, NH and Cao, TN and Hou, G and Yuan, J and Zitzmann, M and Giraldi, A and Jannini, EA}, title = {The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers.}, journal = {Sexual medicine reviews}, volume = {10}, number = {2}, pages = {271-285}, pmid = {34933829}, issn = {2050-0521}, mesh = {Biomarkers ; *COVID-19/complications ; *Erectile Dysfunction/epidemiology ; Humans ; Male ; Quality of Life/psychology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Long term complications of COVID-19, the disease caused by the SARS-CoV-2, involve many organ systems, dramatically worsening the quality of life, and finally contributing to impaired physical functioning. Despite the presence of well-identified pathogenetic mechanisms, the effect of "Long COVID" on sexual health has been only marginally addressed.

OBJECTIVES: To provide coverage of the current literature on long COVID, its epidemiology, pathophysiology, and relevance for erectile function.

METHODS: Comprehensive review of literature pertaining to the epidemiology and pathophysiology of long COVID, and its relevance for erectile function.

RESULTS: Symptoms of long COVID are highly prevalent and involve almost all systems of the human body, with a plethora of clinical manifestations which range from minor nuisances to life-threatening conditions. "Brain fog" and fatigue are the most common complaints, although other neuropsychiatric complications, including sensory dysfunctions, anxiety, depression, and cerebrovascular events have also been reported. The respiratory and cardiovascular systems are also affected, with dyspnea, pulmonary fibrosis, endothelial dysfunction, and myocarditis occurring in some COVID long haulers. A subset of patients might develop endocrine manifestations, including onset of diabetes, thyroid dysfunction, and hypogonadism. Overall, long COVID features many complications which can impair erectile function by multiple pathogenetic mechanisms, and which could require tailored treatment: (i) careful investigation and management from the sexual medicine expert are therefore much needed, (ii) and future research on this topic is warranted.

CONCLUSION: in COVID-19 long haulers, several complications can adversely affect erectile function which, upon future tailored studies, could be used as biomarker for the severity of the long COVID disease and for its follow-up. Sansone A, Mollaioli D, Limoncin E et al. The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers. Sex Med Rev 2022;10:271-285.}, } @article {pmid34932496, year = {2022}, author = {Corman, BHP and Rajupet, S and Ye, F and Schoenfeld, ER}, title = {The Role of Unobtrusive Home-Based Continuous Sensing in the Management of Postacute Sequelae of SARS CoV-2.}, journal = {Journal of medical Internet research}, volume = {24}, number = {1}, pages = {e32713}, pmid = {34932496}, issn = {1438-8871}, mesh = {*COVID-19 ; Disease Progression ; Humans ; Pandemics ; Prevalence ; *SARS-CoV-2 ; }, abstract = {Amid the COVID-19 pandemic, it has been reported that greater than 35% of patients with confirmed or suspected COVID-19 develop postacute sequelae of SARS CoV-2 (PASC). PASC is still a disease for which preliminary medical data are being collected-mostly measurements collected during hospital or clinical visits-and pathophysiological understanding is yet in its infancy. The disease is notable for its prevalence and its variable symptom presentation, and as such, management plans could be more holistically made if health care providers had access to unobtrusive home-based wearable and contactless continuous physiologic and physical sensor data. Such between-hospital or between-clinic data can quantitatively elucidate a majority of the temporal evolution of PASC symptoms. Although not universally of comparable accuracy to gold standard medical devices, home-deployed sensors offer great insights into the development and progression of PASC. Suitable sensors include those providing vital signs and activity measurements that correlate directly or by proxy to documented PASC symptoms. Such continuous, home-based data can give care providers contextualized information from which symptom exacerbation or relieving factors may be classified. Such data can also improve the collective academic understanding of PASC by providing temporally and activity-associated symptom cataloging. In this viewpoint, we make a case for the utilization of home-based continuous sensing that can serve as a foundation from which medical professionals and engineers may develop and pursue long-term mitigation strategies for PASC.}, } @article {pmid34930107, year = {2021}, author = {Chen, C and Amelia, A and Ashdown, GW and Mueller, I and Coussens, AK and Eriksson, EM}, title = {Risk surveillance and mitigation: autoantibodies as triggers and inhibitors of severe reactions to SARS-CoV-2 infection.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {27}, number = {1}, pages = {160}, pmid = {34930107}, issn = {1528-3658}, support = {GNT1161627//National Health and Medical Research Council/ ; GNT1043345//National Health and Medical Research Council/ ; }, mesh = {Animals ; Autoantibodies/*immunology/*metabolism ; Autoimmunity/physiology ; COVID-19/*complications/*immunology/metabolism ; Humans ; SARS-CoV-2/*immunology/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 clinical presentation differs considerably between individuals, ranging from asymptomatic, mild/moderate and severe disease which in some cases are fatal or result in long-term effects. Identifying immune mechanisms behind severe disease development informs screening strategies to predict who are at greater risk of developing life-threatening complications. However, to date clear prognostic indicators of individual risk of severe or long COVID remain elusive. Autoantibodies recognize a range of self-antigens and upon antigen recognition and binding, important processes involved in inflammation, pathogen defence and coagulation are modified. Recent studies report a significantly higher prevalence of autoantibodies that target immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins in COVID-19 patients experiencing severe disease compared to those who experience mild or asymptomatic infections. Here we discuss the diverse impacts of autoantibodies on immune processes and associations with severe COVID-19 disease.}, } @article {pmid34927603, year = {2022}, author = {Kasi, SG and Dhir, SK and Shah, A and Shivananda, S and Verma, S and Marathe, S and Chatterjee, K and Agarwalla, S and Srirampur, S and Kalyani, S and Pemde, HK and Balasubramanian, S and Basavaraja, GV and Parekh, BJ and Kumar, R and Gupta, P and , }, title = {Coronavirus Disease 2019 (COVID-19) Vaccination for Children: Position Statement of Indian Academy of Pediatrics Advisory Committee on Vaccination and Immunization Practices.}, journal = {Indian pediatrics}, volume = {59}, number = {1}, pages = {51-57}, pmid = {34927603}, issn = {0974-7559}, mesh = {Adolescent ; Advisory Committees ; *COVID-19/complications ; COVID-19 Vaccines ; Child ; Child, Preschool ; Humans ; Immunization ; Immunization Schedule ; *Pediatrics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Vaccination ; Post-Acute COVID-19 Syndrome ; }, abstract = {JUSTIFICATION: Data generated after the first wave has revealed that some children with coronavirus 19 (COVID-19) can become seriously ill. Multi-inflammatory syndrome in children (MIS-C) and long COVID cause significant morbidity in children. Prolonged school closures and quarantine have played havoc with the psychosocial health of children. Many countries in the world have issued emergency use authorisation (EUA) of selected Covid-19 vaccines for use in children. In India, a Subject Expert Committee (SEC) has recommended the use of Covaxin (Bharat Biotech) for children from the ages of 2-18 years. The recommendation has been given to the Drugs Controller General of India (DCGI) for final approval.

OBJECTIVE: To provide an evidence-based document to guide the pediatricians on the recommendation to administer COVID vaccines to children, as and when they are available for use.

PROCESS: Formulation of key questions was done by the committee, followed by review of literature on epidemiology and burden of Covid-19 in children, review of the studies on COVID vaccines in children, and the IAP stand on Covid-19 vaccination in children. The available data was discussed in the ACVIP focused WhatsApp group followed by an online meeting on 24 October, 2021, wherein the document was discussed in detail and finalized.

RECOMMENDATIONS: The IAP supports the Government of India's decision to extend the COVID-19 vaccination program to children between 2-18 years of age. Children with high-risk conditions may be immunized on a priority basis. The IAP and its members should be a partner with the Government of India, in the implementation of this program and the surveillance that is necessary following the roll-out.}, } @article {pmid34924675, year = {2022}, author = {Gupta, A and Jain, V and Singh, A}, title = {Stacking Ensemble-Based Intelligent Machine Learning Model for Predicting Post-COVID-19 Complications.}, journal = {New generation computing}, volume = {40}, number = {4}, pages = {987-1007}, pmid = {34924675}, issn = {0288-3635}, abstract = {The recent outbreak of novel coronavirus disease (COVID-19) has resulted in healthcare crises across the globe. Moreover, the persistent and prolonged complications of post-COVID-19 or long COVID are also putting extreme pressure on hospital authorities due to the constrained healthcare resources. Out of many long-lasting post-COVID-19 complications, heart disease has been realized as the most common among COVID-19 survivors. The motivation behind this research is the limited availability of the post-COVID-19 dataset. In the current research, data related to post-COVID complications are collected by personally contacting the previously infected COVID-19 patients. The dataset is preprocessed to deal with missing values followed by oversampling to generate numerous instances, and model training. A binary classifier based on a stacking ensemble is modeled with deep neural networks for the prediction of heart diseases, post-COVID-19 infection. The proposed model is validated against other baseline techniques, such as decision trees, random forest, support vector machines, and artificial neural networks. Results show that the proposed technique outperforms other baseline techniques and achieves the highest accuracy of 93.23%. Moreover, the results of specificity (95.74%), precision (95.24%), and recall (92.05%) also prove the utility of the adopted approach in comparison to other techniques for the prediction of heart diseases.}, } @article {pmid34924406, year = {2021}, author = {Sabel, BA and Zhou, W and Huber, F and Schmidt, F and Sabel, K and Gonschorek, A and Bilc, M}, title = {Non-invasive brain microcurrent stimulation therapy of long-COVID-19 reduces vascular dysregulation and improves visual and cognitive impairment.}, journal = {Restorative neurology and neuroscience}, volume = {39}, number = {6}, pages = {393-408}, pmid = {34924406}, issn = {1878-3627}, mesh = {Adult ; Aged ; Brain ; *COVID-19/complications ; *Cognitive Dysfunction/therapy/virology ; *Electric Stimulation Therapy ; Female ; Humans ; *Vision Disorders/therapy/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: An effective treatment is needed for long-COVID patients which suffer from symptoms of vision and/or cognition impairment such as impaired attention, memory, language comprehension, or fatigue.

OBJECTIVE: Because COVID-19infection causes reduced blood flow which may cause neuronal inactivation, we explored if neuromodulation with non-invasive brain stimulation using microcurrent (NIBS), known to enhance blood flow and neuronal synchronization, can reduce these symptoms.

METHODS: Two female long-COVID patients were treated for 10-13 days with alternating current stimulation of the eyes and brain. While one patient (age 40) was infected with the SARS CoV-2 virus, the other (age 72) developed symptoms following AstraZeneca vaccination. Before and after therapy, cognition was assessed subjectively by interview and visual fields quantified using perimetry. One patient was also tested with a cognitive test battery and with a retinal dynamic vascular analyser (DVA), a surrogate marker of vascular dysregulation in the brain.

RESULTS: In both patients NIBS markedly improved cognition and partially reversed visual field loss within 3-4 days. Cognitive tests in one patient confirmed recovery of up to 40-60% in cognitive subfunctions with perimetry results showing stable and visual field recovery even during follow-up. DVA showed that NIBS reduced vascular dysregulation by normalizing vessel dynamics (dilation/constriction), with particularly noticeable changes in the peripheral veins and arteries.

CONCLUSIONS: NIBS was effective in improving visual and cognitive deficits in two confirmed SARS-COV-2 patients. Because recovery of function was associated with restoration of vascular autoregulation, we propose that (i) hypometabolic, "silent" neurons are the likely biological cause of long-COVID associated visual and cognitive deficits, and (ii) reoxygenation of these "silent" neurons provides the basis for neural reactivation and neurological recovery. Controlled trials are now needed to confirm these observations.}, } @article {pmid34922826, year = {2022}, author = {Patton, LL}, title = {Long-COVID and the practice of oral medicine.}, journal = {Oral surgery, oral medicine, oral pathology and oral radiology}, volume = {133}, number = {2}, pages = {125-128}, pmid = {34922826}, issn = {2212-4411}, mesh = {*COVID-19/complications ; Humans ; Oral Health ; *Oral Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34922734, year = {2022}, author = {Baumber, R and Panagoda, P and Cremin, J and Flynn, P}, title = {Risk stratification of individuals undergoing surgery after COVID 19 recovery. Response to Br J Anaesth 2022; 128: e37-9.}, journal = {British journal of anaesthesia}, volume = {128}, number = {2}, pages = {e57-e58}, pmid = {34922734}, issn = {1471-6771}, mesh = {*COVID-19 ; Humans ; Risk Assessment ; SARS-CoV-2 ; }, } @article {pmid34922127, year = {2022}, author = {Liu, LD and Duricka, DL}, title = {Stellate ganglion block reduces symptoms of Long COVID: A case series.}, journal = {Journal of neuroimmunology}, volume = {362}, number = {}, pages = {577784}, pmid = {34922127}, issn = {1872-8421}, mesh = {Adult ; Autonomic Nerve Block/*methods ; COVID-19/*complications/surgery ; Female ; Humans ; SARS-CoV-2 ; Stellate Ganglion/*surgery ; Post-Acute COVID-19 Syndrome ; }, abstract = {After recovering from COVID-19, a significant proportion of symptomatic and asymptomatic individuals develop Long COVID. Fatigue, orthostatic intolerance, brain fog, anosmia, and ageusia/dysgeusia in Long COVID resemble "sickness behavior," the autonomic nervous system response to pro-inflammatory cytokines (Dantzer et al., 2008). Aberrant network adaptation to sympathetic/parasympathetic imbalance is expected to produce long-standing dysautonomia. Cervical sympathetic chain activity can be blocked with local anesthetic, allowing the regional autonomic nervous system to "reboot." In this case series, we successfully treated two Long COVID patients using stellate ganglion block, implicating dysautonomia in the pathophysiology of Long COVID and suggesting a novel treatment.}, } @article {pmid34921808, year = {2022}, author = {Molteni, E and Bhopal, SS and Hughes, RC and Absoud, M and Duncan, EL and , }, title = {Long COVID in children - Authors' reply.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {1}, pages = {e3}, pmid = {34921808}, issn = {2352-4650}, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34921807, year = {2022}, author = {Gurdasani, D and Akrami, A and Bradley, VC and Costello, A and Greenhalgh, T and Flaxman, S and McKee, M and Michie, S and Pagel, C and Rasmussen, S and Scally, G and Yates, C and Ziauddeen, H}, title = {Long COVID in children.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {1}, pages = {e2}, pmid = {34921807}, issn = {2352-4650}, support = {MR/S003711/1/MRC_/Medical Research Council/United Kingdom ; MR/S003711/2/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34921806, year = {2022}, author = {Mcfarland, S and Citrenbaum, S and Sherwood, O and van der Togt, V and Rossman, JS}, title = {Long COVID in children.}, journal = {The Lancet. Child & adolescent health}, volume = {6}, number = {1}, pages = {e1}, pmid = {34921806}, issn = {2352-4650}, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34921381, year = {2022}, author = {Rafałowicz, B and Wagner, L and Rafałowicz, J}, title = {Long COVID Oral Cavity Symptoms Based on Selected Clinical Cases.}, journal = {European journal of dentistry}, volume = {16}, number = {2}, pages = {458-463}, pmid = {34921381}, issn = {1305-7456}, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by variable clinical features, different durations, and several previously unheard-of late complications. Knowledge about this infection is constantly evolving.The aim of the study is to present selected cases of the most common symptoms of long COVID in the oral cavity.Among the 1,256 studied patients, 32% of them had discoloration, ulceration, and hemorrhagic changes on the oral mucosa, 29.69% had mycosis located on the tongue, 25.79% of patients had aphthous-like lesions on the hard palate, and in 12.5% atrophic cheilitis was observed. During the anamnesis, approximately 60% of patients reported salivary secretory disorders in the initial period of infection, which is 6.68% prolonged up to 4 months after systemic symptoms disappeared. In an extreme case, an aphthous-like lesion was located on the hard palate, which persisted for 6 months. Approximately 36% of patients did not agree to the proposed treatment. As a result, they only received recommendations on the use of oral hygiene products and received weekly check-ups. In this group of patients, most pathological changes spontaneously cleared after 3 weeks. The elderly with coexisting diseases, persons with a more severe SARS-CoV-2, and hospitalized patients had more extensive and severe lesions in the oral cavity that persisted for a long time after infection.In patients after the SARS-CoV-2 infection and suspected of this infection, a detailed intraoral examination should be performed, and the patient must be obligatorily monitored for a minimum period of 6 months. Depending on the patient's clinical condition, changes in the oral cavity require observation, basic or specialist treatment. In the case of changes in the cavity without pain symptoms, observation should be made for approximately 4 weeks and wait for the spontaneous regression of the changes. However, when pain occurs, a good solution is to use laser biostimulation. In the case of complex pathological changes occurring in the oral cavity, the patient should be directed for specialist treatment.}, } @article {pmid34921017, year = {2021}, author = {David, AS}, title = {Long covid: research must guide future management.}, journal = {BMJ (Clinical research ed.)}, volume = {375}, number = {}, pages = {n3109}, doi = {10.1136/bmj.n3109}, pmid = {34921017}, issn = {1756-1833}, mesh = {*Biomedical Research ; COVID-19/*complications/diagnosis/therapy ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34919045, year = {2021}, author = {Chowdhury, F and Grigoriadou, S and Bombardieri, M}, title = {Severity of COVID-19 infection in primary Sjögren's syndrome and the emerging evidence of COVID-19-induced xerostomia.}, journal = {Clinical and experimental rheumatology}, volume = {39 Suppl 133}, number = {6}, pages = {215-222}, doi = {10.55563/clinexprheumatol/k7x3ta}, pmid = {34919045}, issn = {0392-856X}, support = {21268/VAC_/Versus Arthritis/United Kingdom ; MR/N003063/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Autoimmune Diseases ; *COVID-19 ; Humans ; SARS-CoV-2 ; *Sjogren's Syndrome/diagnosis/drug therapy/epidemiology ; *Xerostomia ; }, abstract = {Since the beginning of the COVID-19 disease pandemic caused by the new coronavirus SARS-CoV-2, the disease has claimed over 205M cases (205,338,159) and 4,333,094 deaths (WHO dashboard - accessed 15/08/2021). In addition to the overwhelming impact on healthcare systems treating acutely ill patients, the pandemic has had an impact on all other aspects of health care delivery, including the management of chronic diseases, the risk that is posed in patients with chronic conditions and the risk of the infection itself in those with chronic conditions. Autoimmune rheumatic diseases (ARDs), including primary Sjögren's syndrome (pSS), characterised by immune dysregulation affecting several organs in variable severity, have been of particular interest given the accelerated phase of the immune response in the course of SARS-CoV-2 infection leading to the acute inflammatory response and respiratory distress syndrome or multi-organ failure. On the other hand, the effect of immunosuppressive drug therapies can represent a double edge sword on the course of the disease, either by increased susceptibility to and severity of the infection, or by preventing the accelerated inflammatory response induced by the infection. Additionally, the long-term impact of SARS-CoV-2 infection on the host immune system has led to the onset of novel complex clinical manifestations, comprised under the large umbrella of "long-COVID", which we are only starting to understand. In this review we focus on two interrelated aspects: i) the impact of COVID-19 on patients with pSS and ii) the emerging evidence of long-term xerostomia after SARS-CoV-2 infection.}, } @article {pmid34918990, year = {2022}, author = {Chand, S and Kapoor, S and Naqvi, A and Thakkar, J and Fazzari, MJ and Orsi, D and Dieiev, V and Lewandowski, DC and Dicpinigaitis, PV}, title = {Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19.}, journal = {Journal of intensive care medicine}, volume = {37}, number = {6}, pages = {736-742}, pmid = {34918990}, issn = {1525-1489}, mesh = {*Acute Kidney Injury/epidemiology/etiology/therapy ; *COVID-19/complications ; Critical Illness/therapy ; Female ; Follow-Up Studies ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Renal Replacement Therapy ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes.

METHODS: We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020).

RESULTS: 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge.

CONCLUSION: Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.}, } @article {pmid34918437, year = {2022}, author = {Schneider, SA and Hennig, A and Martino, D}, title = {Relationship between COVID-19 and movement disorders: A narrative review.}, journal = {European journal of neurology}, volume = {29}, number = {4}, pages = {1243-1253}, doi = {10.1111/ene.15217}, pmid = {34918437}, issn = {1468-1331}, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; Humans ; *Movement Disorders/epidemiology/etiology ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: The scientific literature on COVID-19 is increasingly growing.

METHODS: In this paper, we review the literature on movement disorders in the context of the COVID-19 pandemic.

RESULTS: First, there are a variety of transient movement disorders that may manifest in the acute phase of COVID-19, most often myoclonus, with more than 50 patients described in the literature. New onset parkinsonism, chorea, and tic-like behaviours have also been reported. Movement disorders as a side effect after COVID-19 vaccination are rare, occurring with a frequency of 0.00002-0.0002 depending on the product used, mostly manifesting with tremor. Current evidence for potential long-term manifestations, for example, long COVID parkinsonism, is separately discussed. Second, the pandemic has also had an impact on patients with pre-existing movement disorder syndromes, with negative effects on clinical status and overall well-being, and reduced access to medication and health care. In many parts, the pandemic has led to reorganization of the medical system, including the development of new digital solutions. The movement disorder-related evidence for this is reviewed and discussed.

CONCLUSIONS: The pandemic and the associated preventive measures have had a negative impact on the clinical status, access to health care, and overall well-being of patients with pre-existing movement disorders.}, } @article {pmid34918425, year = {2022}, author = {Del Brutto, OH and Rumbea, DA and Recalde, BY and Mera, RM}, title = {Cognitive sequelae of long COVID may not be permanent: A prospective study.}, journal = {European journal of neurology}, volume = {29}, number = {4}, pages = {1218-1221}, doi = {10.1111/ene.15215}, pmid = {34918425}, issn = {1468-1331}, support = {//Universidad de Especialidades Espíritu Santo/ ; }, mesh = {*COVID-19/complications ; Cognition ; *Cognitive Dysfunction/epidemiology/etiology ; Humans ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND PURPOSE: Cognitive decline is a recognized manifestation of long COVID, even among patients who experience mild disease. However, there is no evidence regarding the length of cognitive decline in these patients. This study aimed to assess whether COVID-19-related cognitive decline is a permanent deficit or if it improves over time.

METHODS: Cognitive performance was evaluated by means of the Montreal Cognitive Assessment (MoCA) in COVID-19 survivors and noninfected individuals. All study participants had four cognitive evaluations, two of them before the pandemic and the other two, 6 and 18 months after the initial SARS-CoV-2 outbreak infection in the village. Linear mixed effects models for longitudinal data were fitted to assess differences in cognitive performance across COVID-19 survivors and noninfected individuals.

RESULTS: The study included 78 participants, 50 with history of mild COVID-19 and 28 without. There was a significant-likely age-related-decline in MoCA scores between the two prepandemic tests (β = -1.53, 95% confidence interval [CI] = -2.14 to -0.92, p < 0.001), which did not differ across individuals who later developed COVID-19 when compared to noninfected individuals. Six months after infection, only COVID-19 survivors had a significant decline in MoCA scores (β = -1.37, 95% CI = -2.14 to -0.61, p < 0.001), which reversed after 1 additional year of follow-up (β = 0.66, 95% CI = -0.11 to 1.42, p = 0.092). No differences were noticed among noninfected individuals when both postpandemic MoCA scores were compared.

CONCLUSIONS: Study results suggest that long COVID-related cognitive decline may spontaneously improve over time.}, } @article {pmid34918211, year = {2022}, author = {Santiago-Rodriguez, EI and Maiorana, A and Peluso, MJ and Hoh, R and Tai, V and Fehrman, EA and Hernandez, Y and Torres, L and Spinelli, MA and Gandhi, M and Kelly, JD and Martin, JN and Henrich, TJ and Deeks, SG and Sauceda, JA}, title = {Characterizing the COVID-19 Illness Experience to Inform the Study of Post-acute Sequelae and Recovery.}, journal = {International journal of behavioral medicine}, volume = {29}, number = {5}, pages = {610-623}, pmid = {34918211}, issn = {1532-7558}, support = {P30 MH062246/MH/NIMH NIH HHS/United States ; R01 AI158013/AI/NIAID NIH HHS/United States ; T32 MH019105/MH/NIMH NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; L30 AI147159/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; *COVID-19/complications ; Cohort Studies ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: There is an urgent need to fully understand the impact of variable COVID-19 experiences and the optimal management of post-acute sequelae of SARS-CoV-2 infection. We characterized the variability in the acute illness experience and ongoing recovery process from participants in a COVID-19 recovery cohort study in Northern California in 2020.

METHOD: We completed 24 semi-structured in-depth interviews with adults with confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations. We purposefully sampled English- and Spanish-speaking adults with asymptomatic, mild, and severe symptomatic infection, including those who were hospitalized and those with HIV co-infection. We used a thematic analysis to analyze interviews and identify salient themes.

RESULTS: After integrating the thematic analysis with clinical data, we identified key themes: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress; (2) symptomatic infection carried uncertainty in symptom presentation and ongoing recovery (e.g., long COVID); and (3) health information-seeking behavior was facilitated by access to medical care and uncertainty with the recovery process.

CONCLUSION: Our data informs the emerging field of "long COVID" research and shows a need to provide information and continuous support to persons with post-acute sequelae to ensure they feel secure along the path to recovery.}, } @article {pmid34917659, year = {2021}, author = {Charfeddine, S and Ibn Hadj Amor, H and Jdidi, J and Torjmen, S and Kraiem, S and Hammami, R and Bahloul, A and Kallel, N and Moussa, N and Touil, I and Ghrab, A and Elghoul, J and Meddeb, Z and Thabet, Y and Kammoun, S and Bouslama, K and Milouchi, S and Abdessalem, S and Abid, L}, title = {Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study.}, journal = {Frontiers in cardiovascular medicine}, volume = {8}, number = {}, pages = {745758}, pmid = {34917659}, issn = {2297-055X}, abstract = {The COVID-19 disease is a multisystem disease due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated with endothelial dysfunction. This is a cross-sectional multicenter observational study with prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95-2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain, and neuro-cognitive difficulties were significantly associated with endothelium dysfunction with an EQI <2 after adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI <2), female gender, and severe clinical status at acute COVID-19 infection with a need for oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms, specifically non-respiratory symptoms, are due to persistent endothelial dysfunction. These findings allow for better care of patients with long COVID-19 symptoms.}, } @article {pmid34917633, year = {2021}, author = {Barros, CMSS and Freire, RS and Frota, E and Rezende Santos, AG and Farias, MEL and Rodrigues, MGA and Silva, BM and Prado Jeronimo, CM and Netto, RLA and Silva Borba, MG and Baía-da-Silva, D and Brito-Sousa, JD and Xavier, MS and Araújo-Alexandre, MA and Sampaio, VS and Melo, GC and Arêas, GT and Hajjar, LA and Monteiro, WM and Gomes Naveca, F and Costa, FTM and Val, FFA and Lacerda, MVG and , }, title = {Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {758405}, pmid = {34917633}, issn = {2296-858X}, abstract = {Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days. Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical-radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit. Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission. Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis. Trial Registration: ClinicalTrials.gov, Identifier: NCT04343729.}, } @article {pmid34913540, year = {2024}, author = {Cha, C and Baek, G}, title = {Symptoms and management of long COVID: A scoping review.}, journal = {Journal of clinical nursing}, volume = {33}, number = {1}, pages = {11-28}, doi = {10.1111/jocn.16150}, pmid = {34913540}, issn = {1365-2702}, mesh = {Humans ; *COVID-19/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics ; COVID-19 Drug Treatment ; Fatigue ; Cough ; }, abstract = {AIM: This scoping review aims to describe published work on the symptoms and management of long COVID conditions.

BACKGROUND: Symptoms and management of COVID-19 have focused on the acute stage. However, long-term consequences have also been observed.

METHODS: A scoping review was performed based on the framework suggested by Arksey and O'Malley. We conducted a literature search to retrieve articles published from May 2020 to March 2021 in CINHAL, Cochrane library, Embase, PubMed and Web of science, including backward and forward citation tracking from the included articles. Among the 1880 articles retrieved, 34 articles met our criteria for review: 21 were related to symptom presentation and 13 to the management of long COVID.

RESULTS: Long COVID symptoms were described in 21 articles. Following COVID-19 treatment, hospitalised patients most frequently reported dyspnoea, followed by anosmia/ageusia, fatigue and cough, while non-hospitalised patients commonly reported cough, followed by fever and myalgia/arthralgia. Thirteen studies described management for long COVID: Focused on a multidisciplinary approach in seven articles, pulmonary rehabilitation in three articles, fatigue management in two articles and psychological therapy in one study.

CONCLUSION: People experience varied COVID-19 symptoms after treatment. However, guidelines on evidence-based, multidisciplinary management for long COVID conditions are limited in the literature. The COVID-19 pandemic may extend due to virus mutations; therefore, it is crucial to develop and disseminate evidence-based, multidisciplinary management guidelines.

A rehabilitation care plan and community healthcare plans are necessary for COVID-19 patients before discharge. Remote programmes could facilitate the monitoring and screening of people with long COVID.}, } @article {pmid34912599, year = {2021}, author = {Vera-Lastra, O and Lucas-Hernández, A and Ruiz-Montiel, JE and Gonzalez-Rodriguez, VR and Pineda-Galindo, LF}, title = {Myopericarditis as a Manifestation of Long COVID Syndrome.}, journal = {Cureus}, volume = {13}, number = {11}, pages = {e19449}, pmid = {34912599}, issn = {2168-8184}, abstract = {The main presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is respiratory. However, there are extrapulmonary manifestations such as myocardial and pericardial injury. The term long COVID syndrome describes the persistence of symptoms in patients who have recovered from the infection. A 31-year-old man presented with mild coronavirus disease 2019 (COVID-19) symptoms for three days. Two weeks later, he developed chest pain, pericardial rub, and pericardial effusion; he underwent echocardiography showing pericarditis and an MRI which revealed inferoseptal hypokinesia and mild global myocardial hyperintensity, cardiac scintigraphy with Ga-67, and an inflammatory process in the myocardium. He was treated with methylprednisolone pulse (1g IV/day) and tapering prednisone (5 mg/day), with gradual evolution of symptoms for one year. In conclusion, this is a patient without comorbidities with clinical, laboratory, and imaging diagnosis of myopericarditis as a manifestation of long COVID syndrome.}, } @article {pmid34912345, year = {2021}, author = {Emadi-Baygi, M and Ehsanifard, M and Afrashtehpour, N and Norouzi, M and Joz-Abbasalian, Z}, title = {Corona Virus Disease 2019 (COVID-19) as a System-Level Infectious Disease With Distinct Sex Disparities.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {778913}, pmid = {34912345}, issn = {1664-3224}, mesh = {Biomarkers ; Blood Coagulation ; Blood Coagulation Disorders/diagnosis/etiology ; COVID-19/complications/diagnosis/*epidemiology/*virology ; Cytokines/metabolism ; Disease Susceptibility ; Endothelium/metabolism ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation Mediators ; Male ; Renin-Angiotensin System ; *SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; }, abstract = {The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.}, } @article {pmid34911690, year = {2021}, author = {Torjesen, I}, title = {Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest.}, journal = {BMJ (Clinical research ed.)}, volume = {375}, number = {}, pages = {n3092}, doi = {10.1136/bmj.n3092}, pmid = {34911690}, issn = {1756-1833}, } @article {pmid34906986, year = {2021}, author = {Hossain, MA and Hossain, KMA and Saunders, K and Uddin, Z and Walton, LM and Raigangar, V and Sakel, M and Shafin, R and Hossain, MS and Kabir, MF and Faruqui, R and Rana, MS and Ahmed, MS and Chakrovorty, SK and Hossain, MA and Jahid, IK}, title = {Prevalence of Long COVID symptoms in Bangladesh: a prospective Inception Cohort Study of COVID-19 survivors.}, journal = {BMJ global health}, volume = {6}, number = {12}, pages = {}, pmid = {34906986}, issn = {2059-7908}, mesh = {Activities of Daily Living ; Bangladesh/epidemiology ; *COVID-19/complications ; COVID-19 Testing ; Cohort Studies ; Female ; Humans ; Oxygen Saturation ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The objective of this study was to identify the prevalence of long COVID symptoms in a large cohort of people living with and affected by long COVID and identify any potential associated risk factors.

METHODS: A prospective survey was undertaken of an inception cohort of confirmed people living with and affected by long COVID (aged 18-87 years). 14392 participants were recruited from 24 testing facilities across Bangladesh between June and November 2020. All participants had a previously confirmed positive COVID-19 diagnosis, and reported persistent symptoms and difficulties in performing daily activities. Participants who consented were contacted by face-to-face interview, and were interviewed regarding long COVID, and restriction of activities of daily living using post COVID-19 functional status scale. Cardiorespiratory parameters measured at rest (heart rate, systolic blood pressure, diastolic blood pressure, oxygen saturation levels, maximal oxygen consumption, inspiratory and expiratory lung volume) were also measured.

RESULTS: Among 2198 participants, the prevalence of long COVID symptoms at 12 weeks was 16.1%. Overall, eight long COVID symptoms were identified and in descending order of prominence are: fatigue, pain, dyspnoea, cough, anosmia, appetite loss, headache and chest pain. People living with and affected by long COVID experienced between 1 and 8 long COVID symptoms with an overall duration period of 21.8±5.2 weeks. Structural equation modelling predicted the length of long COVID to be related to younger age, female gender, rural residence, prior functional limitation and smoking.

CONCLUSION: In this cohort, at 31 weeks post diagnosis, the prevalence of long COVID symptoms was 16.1%. The risk factors identified for presence and longer length of long COVID symptoms warrant further research and consideration to support public health initiatives.}, } @article {pmid34906823, year = {2022}, author = {Roth, PH and Gadebusch-Bondio, M}, title = {The contested meaning of "long COVID" - Patients, doctors, and the politics of subjective evidence.}, journal = {Social science & medicine (1982)}, volume = {292}, number = {}, pages = {114619}, pmid = {34906823}, issn = {1873-5347}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; Politics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In our article, we reconstruct how the patient-made term "long COVID" was able to become a widely accepted concept in public discourses. While the condition was initially invisible to the public eye, we show how the mobilization of subjective evidence online, i.e., the dissemination of reports on the different experiences of lasting symptoms, was able to transform the condition into a crucial feature of the coronavirus pandemic. We explore how stakeholders used the term "long COVID" in online media and in other channels to create their illness and group identity, but also to demarcate the personal experience and experiential knowledge of long COVID from that of other sources. Our exploratory study addresses two questions. Firstly, how the mobilization of subjective evidence leads to the recognition of long COVID and the development of treatment interventions in medicine; and secondly, what distinguishes these developments from other examples of subjective evidence mobilization. We argue that the long COVID movement was able to fill crucial knowledge gaps in the pandemic discourses, making long COVID a legitimate concern of official measures to counter the pandemic. By first showing how illness experiences were gathered that defied official classifications of COVID-19, we show how patients made the "long COVID" term. Then we compare the clinical and social identity of long COVID to that of chronic fatigue syndrome (ME/CFS), before we examine the social and epistemic processes at work in the digital and medial discourses that have transformed how the pandemic is perceived through the lens of long COVID. Building on this, we finally demonstrate how the alignment of medical professionals as patients with the movement has challenged the normative role of clinical evidence, leading to new forms of medical action to tackle the pandemic.}, } @article {pmid34905407, year = {2022}, author = {Miller, L and Berber, E and Sumbria, D and Rouse, BT}, title = {Controlling the Burden of COVID-19 by Manipulating Host Metabolism.}, journal = {Viral immunology}, volume = {35}, number = {1}, pages = {24-32}, pmid = {34905407}, issn = {1557-8976}, support = {R21 AI142862/AI/NIAID NIH HHS/United States ; R01 EY005093/EY/NEI NIH HHS/United States ; }, mesh = {*COVID-19/metabolism/therapy ; *Cost of Illness ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause global health problems, but its impact would be minimized if the many effective vaccines that have been developed were available and in widespread use by all societies. This ideal situation is not occurring so other means of controlling COVID-19 are needed. In this short review, we make the case that manipulating host metabolic pathways could be a therapeutic approach worth exploring. The rationale for such an approach comes from the fact that viruses cause metabolic changes in cells they infect, effective host defense mechanisms against viruses requires the activity of one or more metabolic pathways, and that hosts with metabolic defects such as diabetes are more susceptible to severe consequences after COVID-19. We describe the types of approaches that could be used to redirect various aspects of host metabolism and the success that some of these maneuvers have had at controlling other virus infections. Manipulating metabolic activities to control the outcome of COVID-19 has to date received minimal attention. Manipulating host metabolism will never replace vaccines to control COVID-19 but could be used as an adjunct therapy to the extent of ongoing infection.}, } @article {pmid34903448, year = {2022}, author = {Fumagalli, C and Zocchi, C and Tassetti, L and Silverii, MV and Amato, C and Livi, L and Giovannoni, L and Verrillo, F and Bartoloni, A and Marcucci, R and Lavorini, F and Fumagalli, S and Ungar, A and Olivotto, I and Rasero, L and Fattirolli, F and Marchionni, N and , }, title = {Factors associated with persistence of symptoms 1 year after COVID-19: A longitudinal, prospective phone-based interview follow-up cohort study.}, journal = {European journal of internal medicine}, volume = {97}, number = {}, pages = {36-41}, pmid = {34903448}, issn = {1879-0828}, mesh = {*COVID-19/complications ; Cohort Studies ; Follow-Up Studies ; Humans ; Prospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To investigate the persistence of symptoms compatible with COVID-19 in a real-file prospective cohort of patients at 12 months from hospital discharge.

METHODS: Longitudinal, prospective, single-center, cohort telephone follow-up (FU) study in a Tertiary Care Hospital. All consecutive patients >18 years admitted for COVID-19 were prospectively enrolled in a telephone FU program aimed at monitoring symptoms after 1,3,6,9 and 12 months from hospital discharge. The survey screened for somatic (fatigue, dyspnea, dyspnea, palpitations, cough, chest pain, abdominal pain, ageusia, anosmia, bowel symptoms) and emotional symptoms (insomnia, confusion, altered sense of reality, loss of appetite, fear, and depression) and frailty. Only patients with 12 months FU data were analyzed (N=254). Prevalence and factors associated with symptoms were the main outcomes. Frailty was defined by the presence of ≥3 indicators: weakness, slowness/impaired mobility, weight-loss, low physical activity, and exhaustion.

RESULTS: At 12 months, 40.5% of patients reported at least one symptom. The most common somatic ones were fatigue, exertional dyspnea, cough, bowel complaints while the most common psycho-emotional were insomnia, confusion, fear, and depression. Age, gender, gender, frailty, multiple symptoms at baseline and chronic obstructive pulmonary disease (COPD) were associated with symptoms persistence. Furthermore, frailty, COPD and multiple symptoms at baseline were associated with increased risk of somatic symptoms at 12 months, while age and gender were associated with emotional ones.

CONCLUSIONS: Burden of the long COVID-19 symptoms decreased over time but remained as high as 40% at 12 months with important gender and functional differences, highlighting potential patient categories who may benefit from specific follow up strategies.}, } @article {pmid34899999, year = {2022}, author = {Shimohata, T}, title = {Neuro-COVID-19.}, journal = {Clinical & experimental neuroimmunology}, volume = {13}, number = {1}, pages = {17-23}, pmid = {34899999}, issn = {1759-1961}, abstract = {Neuromuscular manifestations of new coronavirus disease 2019 (COVID-19) infection are frequent, and include dizziness, headache, myopathy, and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate. The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS-CoV-2 virus, encephalopathy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune-mediated encephalitis that occurs after infection. The sequelae, called post-acute COVID-19 syndrome or long COVID, include neuromuscular manifestations, such as anxiety, depression, sleep disturbance, muscle weakness, brain fog and cognitive impairment. It is desirable to establish diagnostic criteria and treatment for these symptoms. Vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, bilateral facial paralysis, encephalitis and opsoclonus-myoclonus syndrome have been reported as adverse reactions after the COVID-19 vaccine, although these are rare.}, } @article {pmid34899105, year = {2021}, author = {Sims, S and Fletcher, S and Brearley, S and Ross, F and Manthorpe, J and Harris, R}, title = {What does Success Look Like for Leaders of Integrated Health and Social Care Systems? a Realist Review.}, journal = {International journal of integrated care}, volume = {21}, number = {4}, pages = {26}, pmid = {34899105}, issn = {1568-4156}, abstract = {INTRODUCTION: Health and social care services in England are moving towards greater integration, yet little is known about how leadership of integrated care teams and systems can be supported and improved. This realist review explores what works about the leadership of integrated care teams and systems, for whom, in what circumstances and why.

METHODS: A realist synthesis approach was undertaken in 2020 to explore English language literature on the leadership of integrated care teams and systems, complemented by ongoing stakeholder consultation.

RESULTS: Evidence was identified for seven potentially important components of leadership in integrated care teams and systems: 'inspiring intent to work together'; 'creating the conditions'; 'balancing multiple perspectives'; 'working with power'; 'taking a wider view'; 'a commitment to learning and development' and 'clarifying complexity'.

DISCUSSION: Research into the leadership of integrated care teams and systems is limited, with ideas often reverting to existing framings of leadership, where teams and organisations are less complex. Research also often focuses on the importance of who the leader is rather than what they do.

CONCLUSION: This review has generated new perspectives on the leadership of integrated care teams and systems that can be built upon, developed, and tested further.}, } @article {pmid34897635, year = {2021}, author = {Evrin, T and Katipoglu, B}, title = {COVID-19 are dangerous to the kidneys in any situation, not only in a pandemic: LONG-COVID-19 and kidney disease.}, journal = {Cardiology journal}, volume = {28}, number = {6}, pages = {1005-1006}, pmid = {34897635}, issn = {1898-018X}, mesh = {*COVID-19/complications ; Humans ; Kidney/physiopathology ; *Kidney Diseases/virology ; Pandemics ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34895935, year = {2022}, author = {Raw, RK and Rees, J and Kelly, CA and Wroe, C and Chadwick, DR}, title = {Prior COVID-19 infection is associated with increased Adverse Events (AEs) after the first, but not the second, dose of the BNT162b2/Pfizer vaccine.}, journal = {Vaccine}, volume = {40}, number = {3}, pages = {418-423}, pmid = {34895935}, issn = {1873-2518}, mesh = {*BNT162 Vaccine ; *COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; SARS-CoV-2 ; Vaccination Hesitancy ; }, abstract = {The BNT162b2/Pfizer SARS-CoV-2 vaccine has been widely used in the UK, particularly amongst healthcare workers (HCWs). To establish whether previous COVID-19 influenced vaccine-associated Adverse Events (AEs), we conducted a survey-based study of HCWs in Northeast England. Out of 1238 HCWs, 32% self-reported prior positive PCR and/or antibody test for SARS-CoV-2. Post-dose AEs were worse in those with prior COVID-19 after the first, but not the second dose of vaccine. Second dose AEs were greater in frequency/severity, regardless of COVID-19 history, and they were more systemic in nature. Women and younger HCW were more likely to report AEs after both doses, while dosing interval had no effect on AEs. Ongoing Symptomatic COVID-19 was associated with greater frequency/severity of AEs after dose 2, but not dose one. Overall, AEs were self-limiting and short-lived (i.e.,<48 h) in nature. These findings have implications for vaccine hesitancy and informing guidelines for recommended dosing protocols.}, } @article {pmid34893782, year = {2021}, author = {Baker, N and Ledford, H}, title = {Coronapod: vaccines and long COVID, how protected are you?.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-021-03732-8}, pmid = {34893782}, issn = {1476-4687}, } @article {pmid34893773, year = {2021}, author = {van der Togt, V and Mcfarland, S and Esperti, M and Semper, E and Citrenbaum, S and Rossman, JS}, title = {Promotion of non-evidence-based therapeutics within patient-led Long COVID support groups.}, journal = {Nature medicine}, volume = {27}, number = {12}, pages = {2068-2069}, pmid = {34893773}, issn = {1546-170X}, mesh = {COVID-19/*complications/therapy/virology ; Evidence-Based Medicine ; Health Promotion/*methods ; Humans ; SARS-CoV-2/isolation & purification ; *Self-Help Groups ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34890036, year = {2021}, author = {Naureen, Z and Dautaj, A and Nodari, S and Fioretti, F and Dhuli, K and Anpilogov, K and Lorusso, L and Paolacci, S and Michelini, S and Guda, T and Kallazi, M and Bertelli, M}, title = {Proposal of a food supplement for the management of post-COVID syndrome.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {1 Suppl}, pages = {67-73}, doi = {10.26355/eurrev_202112_27335}, pmid = {34890036}, issn = {2284-0729}, mesh = {Acetylcarnitine/administration & dosage ; Adult ; Aged ; COVID-19/*complications/diet therapy/pathology/psychology/virology ; *Dietary Supplements/adverse effects ; Fatigue/etiology ; Female ; Gastrointestinal Diseases/etiology ; Humans ; Male ; Middle Aged ; Phenylethyl Alcohol/administration & dosage/analogs & derivatives ; Pilot Projects ; SARS-CoV-2/isolation & purification ; Self Report ; Surveys and Questionnaires ; Vitamins/administration & dosage ; Post-Acute COVID-19 Syndrome ; }, abstract = {A vast majority of COVID-19 patients experience fatigue, extreme tiredness and symptoms that persist beyond the active phase of the disease. This condition is called post-COVID syndrome. The mechanisms by which the virus causes prolonged illness are still unclear. The aim of this review is to gather information regarding post-COVID syndrome so as to highlight its etiological basis and the nutritional regimes and supplements that can mitigate, alleviate or relieve the associated chronic fatigue, gastrointestinal disorders and continuing inflammatory reactions. Naturally-occurring food supplements, such as acetyl L-carnitine, hydroxytyrosol and vitamins B, C and D hold significant promise in the management of post-COVID syndrome. In this pilot observational study, we evaluated the effect of a food supplement containing hydroxytyrosol, acetyl L-carnitine and vitamins B, C and D in improving perceived fatigue in patients who recovered from COVID-19 but had post-COVID syndrome characterized by chronic fatigue. The results suggest that the food supplement could proceed to clinical trials of its efficacy in aiding the recovery of patients with long COVID.}, } @article {pmid34889531, year = {2022}, author = {Jozuka, R and Kimura, H and Uematsu, T and Fujigaki, H and Yamamoto, Y and Kobayashi, M and Kawabata, K and Koike, H and Inada, T and Saito, K and Katsuno, M and Ozaki, N}, title = {Severe and long-lasting neuropsychiatric symptoms after mild respiratory symptoms caused by COVID-19: A case report.}, journal = {Neuropsychopharmacology reports}, volume = {42}, number = {1}, pages = {114-119}, pmid = {34889531}, issn = {2574-173X}, support = {JP21dk0307099//AMED/ ; JP21dk0307103//AMED/ ; 21H02848//Japan Society for the Promotion of Science/ ; }, mesh = {*COVID-19/complications ; Fatigue ; Female ; Humans ; *Mental Disorders ; Middle Aged ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID-19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID-19 remain poorly understood. Here, we present a case of COVID-19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms.

CASE PRESENTATION: A 55-year-old female with COVID-19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post-COVID-19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained.

CONCLUSIONS: This case suggests the importance of both recognizing that even apparently mild COVID-19-related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long-term course of COVID-19-related neuropsychiatric symptoms in the future.}, } @article {pmid34889154, year = {2022}, author = {Roesler, M and Fato, P and Obst, B}, title = {Long COVID-The New "Invisible" Illness: How School Nurses Can Support the Nursing and Educational Teams for Student Success.}, journal = {NASN school nurse (Print)}, volume = {37}, number = {2}, pages = {90-95}, doi = {10.1177/1942602X211059427}, pmid = {34889154}, issn = {1942-6038}, mesh = {*COVID-19/complications ; Child ; Humans ; *Return to School ; SARS-CoV-2 ; *School Nursing ; Students ; Post-Acute COVID-19 Syndrome ; }, abstract = {School-age children are not immune to COVID-19 or the pronounced and persistent symptoms associated with a long-COVID diagnosis. Students may present with a variety of symptoms affecting their physical, cognitive, and mental health. The school community should be educated on the school-based interventions and recommendations for creating an individualized safe and successful return to school plan. As we await approval for vaccinations in school-age children younger than 12 years and continue to reposition ourselves to the waves of this pandemic and new variants of the virus, understanding the medical and educational long-term effects on our students may be a long-term need.}, } @article {pmid34888989, year = {2022}, author = {Yong, SJ and Liu, S}, title = {Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies.}, journal = {Reviews in medical virology}, volume = {32}, number = {4}, pages = {e2315}, doi = {10.1002/rmv.2315}, pmid = {34888989}, issn = {1099-1654}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; Humans ; Pandemics ; *Postural Orthostatic Tachycardia Syndrome/diagnosis/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The effects of coronavirus disease 2019 (COVID-19), a highly transmissible infectious respiratory disease that has initiated an ongoing pandemic since early 2020, do not always end in the acute phase. Depending on the study referred, about 10%-30% (or more) of COVID-19 survivors may develop long-COVID or post-COVID-19 syndrome (PCS), characterised by persistent symptoms (most commonly fatigue, dyspnoea, and cognitive impairments) lasting for 3 months or more after acute COVID-19. While the pathophysiological mechanisms of PCS have been extensively described elsewhere, the subtypes of PCS have not. Owing to its highly multifaceted nature, this review proposes and characterises six subtypes of PCS based on the existing literature. The subtypes are non-severe COVID-19 multi-organ sequelae (NSC-MOS), pulmonary fibrosis sequelae (PFS), myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), post-intensive care syndrome (PICS) and medical or clinical sequelae (MCS). Original studies supporting each of these subtypes are documented in this review, as well as their respective symptoms and potential interventions. Ultimately, the subtyping proposed herein aims to provide better clarity on the current understanding of PCS.}, } @article {pmid34884276, year = {2021}, author = {Salvatori, S and Baldassarre, F and Mossa, M and Monteleone, G}, title = {Long COVID in Inflammatory Bowel Diseases.}, journal = {Journal of clinical medicine}, volume = {10}, number = {23}, pages = {}, pmid = {34884276}, issn = {2077-0383}, abstract = {BACKGROUND AND AIMS: SARS-CoV-2-infected patients can experience long-lasting symptoms even after the resolution of the acute infection. This condition, defined as Long COVID, is now recognized as a public health priority and its negative impact on the quality of life of the patients could be more relevant in individuals with debilitating pathologies. We here evaluated the frequency of Long COVID in patients with inflammatory bowel diseases (IBD).

METHODS: IBD patients afferent for scheduled visits to our tertiary referral center at the Tor Vergata University Hospital, Rome, were recruited from 7 September to 22 October 2021. During the visits, patients were investigated about previous COVID-19 infection and the possible development of Long COVID.

RESULTS: Fifty-three out of 528 IBD patients (10%) have had a SARS-CoV-2 infection. Of these, 21 patients (40%) developed Long COVID, and asthenia was the more frequent symptom as it occurred in nearly two-thirds of patients. Patients with Long COVID were more frequently females, while other clinical and demographic characteristics did not differ between patients with Long COVID and those without Long COVID. In particular, the IBD relapses occurred with the same frequency in the two groups.

CONCLUSIONS: Long COVID appears to be common in IBD patients even though it does not influence the IBD course.}, } @article {pmid34884216, year = {2021}, author = {Vallée, A}, title = {Dysautonomia and Implications for Anosmia in Long COVID-19 Disease.}, journal = {Journal of clinical medicine}, volume = {10}, number = {23}, pages = {}, pmid = {34884216}, issn = {2077-0383}, abstract = {Long COVID-19 patients often reported anosmia as one of the predominant persisting symptoms. Recent findings have shown that anosmia is associated with neurological dysregulations. However, the involvement of the autonomic nervous system (ANS), which can aggregate all the long COVID-19 neurological symptoms, including anosmia, has not received much attention in the literature. Dysautonomia is characterized by the failure of the activities of components in the ANS. Long COVID-19 anosmia fatigue could result from damage to olfactory sensory neurons, leading to an augmentation in the resistance to cerebrospinal fluid outflow by the cribriform plate, and further causing congestion of the glymphatic system with subsequent toxic build-up in the brain. Studies have shown that anosmia was an important neurologic symptom described in long COVID-19 in association with potential COVID-19 neurotropism. SARS-CoV-2 can either travel via peripheral blood vessels causing endothelial dysfunction, triggering coagulation cascade and multiple organ dysfunction, or reach the systemic circulation and take a different route to the blood-brain barrier, damaging the blood-brain barrier and leading to neuroinflammation and neuronal excitotoxicity. SARS-CoV-2 entry via the olfactory epithelium and the increase in the expression of TMPRSS2 with ACE2 facilitates SARS-CoV-2 neurotropism and then dysautonomia in long COVID-19 patients. Due to this effect, patients with anosmia persisting 3 months after COVID-19 diagnosis showed extensive destruction of the olfactory epithelium. Persistent anosmia observed among long COVID-19 patients may be involved by a cascade of effects generated by dysautonomia leading to ACE2 antibodies enhancing a persistent immune activation.}, } @article {pmid34882720, year = {2021}, author = {Kisiel, MA and Nordqvist, T and Westman, G and Svartengren, M and Malinovschi, A and Janols, H}, title = {Patterns and predictors of sick leave among Swedish non-hospitalized healthcare and residential care workers with Covid-19 during the early phase of the pandemic.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260652}, pmid = {34882720}, issn = {1932-6203}, mesh = {Adult ; COVID-19/*epidemiology/virology ; Comorbidity ; Depression/diagnosis ; Dyspnea/diagnosis ; Female ; Health Personnel/*psychology ; Humans ; Male ; Middle Aged ; Pandemics ; Risk ; SARS-CoV-2/isolation & purification ; Sick Leave/*statistics & numerical data ; Sweden/epidemiology ; }, abstract = {Healthcare and residential care workers represent two occupational groups that have, in particular, been at risk of Covid-19, its long-term consequences, and related sick leave. In this study, we investigated the predictors of prolonged sick leave among healthcare and residential workers due to non-hospitalized Covid-19 in the early period of the pandemic. This study is based on a patient register (n = 3209) and included non-hospitalized healthcare or residential care service workers with a positive RT- PCR for SARS-CoV-2 (n = 433) between March and August 2020. Data such as socio-demographics, clinical characteristics, and the length of sick leave because of Covid-19 and prior to the pandemic were extracted from the patient's electronic health records. Prolonged sick leave was defined as sick leave ≥ 3 weeks, based on the Swedish pandemic policy. A generalized linear model was used with a binary distribution, adjusted for age, gender, and comorbidity in order to predict prolonged sick leave. Of 433 (77% women) healthcare and residential care workers included in this study, 14.8% needed longer sick leave (> 3 weeks) due to Covid-19. Only 1.4% of the subjects were on sick leave because of long Covid. The risk of sick leave was increased two-fold among residential care workers (adjusted RR 2.14 [95% CI 1.31-3.51]). Depression/anxiety (adjusted RR 2.09 [95% CI 1.31-3.34]), obesity (adjusted RR 1.96 [95% CI 1.01-3.81]) and dyspnea at symptom onset (adjusted RR 2.47 [95% CI 1.55-3.92]), sick leave prior to the pandemic (3-12 weeks) (adjusted RR 2.23 [95% CI 1.21-4.10]) were associated with longer sick leave. From a public health perspective, considering occupational category, comorbidity, symptoms at onset, and sick leave prior to the pandemic as potential predictors of sick leave in healthcare may help prevent staff shortage.}, } @article {pmid34882130, year = {2021}, author = {Nune, A and Durkowski, V and Titman, A and Gupta, L and Hadzhiivanov, M and Ahmed, A and Musat, C and Sapkota, HR}, title = {Incidence and risk factors of long COVID in the UK: a single-centre observational study.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {51}, number = {4}, pages = {338-343}, doi = {10.4997/JRCPE.2021.405}, pmid = {34882130}, issn = {2042-8189}, mesh = {*COVID-19/complications ; Humans ; Incidence ; Risk Factors ; SARS-CoV-2 ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Studies to evaluate long COVID symptoms and their risk factors are limited. We evaluated the presence of long COVID and its risk factors in patients discharged from a hospital with COVID-19 illness.

METHODS: This observational study included 271 COVID-19 patients admitted between February and July 2020 in a hospital in the UK. The primary outcome measure was to assess the duration and severity of long COVID and its predictors at 3, 6 and 9 months. Logistic regression was performed to assess the potential risk factors for long COVID.

RESULTS: Out of 89 patients interviewed, 55 (62%) had long COVID for 3 months, 46 (52%) for 6 months and 37 of the 75 patients admitted to the hospital with acute COVID-19 had long COVID for 9 months (49%). The most common long COVID symptoms were fatigue and breathlessness.

CONCLUSION: Nearly two-thirds of patients at 3 months and a half at 9 months had long COVID. COVID-19 pneumonia was the strongest predictor of long COVID in Caucasians at 3 months.}, } @article {pmid34881263, year = {2021}, author = {Wu, L and Wu, Y and Xiong, H and Mei, B and You, T}, title = {Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {761314}, pmid = {34881263}, issn = {2296-858X}, abstract = {Many patients who had coronavirus disease 2019 (COVID-19) had at least one symptom that persisted after recovery from the acute phase. Our purpose was to review the empirical evidence on symptom prevalence, complications, and management of patients with long COVID. We systematically reviewed the literature on the clinical manifestations of long COVID-19, defined by the persistence of symptoms beyond the acute phase of infection. Bibliographic searches in PubMed and Google Scholar were conducted to retrieve relevant studies on confirmed patients with long COVID that were published prior to August 30, 2021. The most common persistent symptoms were fatigue, cough, dyspnea, chest pains, chest tightness, joint pain, muscle pain, loss of taste or smell, hair loss, sleep difficulties, anxiety, and depression. Some of the less common persistent symptoms were skin rash, decreased appetite, sweating, inability to concentrate, and memory lapses. In addition to these general symptoms, some patients experienced dysfunctions of specific organs, mainly the lungs, heart, kidneys, and nervous system. A comprehensive understanding of the persistent clinical manifestations of COVID-19 can improve and facilitate patient management and referrals. Prompt rehabilitative care and targeted interventions of these patients may improve their recovery from physical, immune, and mental health symptoms.}, } @article {pmid34880476, year = {2021}, author = {Graham, F}, title = {Daily briefing: What we know about vaccines and long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-021-03531-1}, pmid = {34880476}, issn = {1476-4687}, } @article {pmid34877576, year = {2021}, author = {Kanduc, D}, title = {From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity.}, journal = {Global medical genetics}, volume = {8}, number = {4}, pages = {176-182}, pmid = {34877576}, issn = {2699-9404}, abstract = {Background and Objectives Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins. Materials and Methods Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases. Results An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena. Conclusion This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic.}, } @article {pmid34877261, year = {2022}, author = {Bansal, R and Gubbi, S and Koch, CA}, title = {COVID-19 and chronic fatigue syndrome: An endocrine perspective.}, journal = {Journal of clinical & translational endocrinology}, volume = {27}, number = {}, pages = {100284}, pmid = {34877261}, issn = {2214-6237}, abstract = {Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs. Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help. Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenal and thyroid function. We here review the literature and potential pathophysiological mechanisms involved in and related to post COVID-19 symptoms with an emphasis on endocrine function.}, } @article {pmid34876772, year = {2022}, author = {Vallejo Camazón, N and Teis, A and Martínez Membrive, MJ and Llibre, C and Bayés-Genís, A and Mateu, L}, title = {[Long COVID-19 and microvascular disease-related angina].}, journal = {Revista espanola de cardiologia}, volume = {75}, number = {5}, pages = {444-446}, pmid = {34876772}, issn = {1579-2242}, } @article {pmid34875129, year = {2022}, author = {Lam, GY and Befus, D and Damant, RW and Ferrara, G and Fuhr, DP and Laratta, CR and Lau, A and Stickland, MK and Varughese, RA and Wong, EY and Smith, MP}, title = {COVID-19 hospitalization is associated with pulmonary/diffusion abnormalities but not post-acute sequelae of COVID-19 severity.}, journal = {Journal of internal medicine}, volume = {291}, number = {5}, pages = {694-697}, doi = {10.1111/joim.13427}, pmid = {34875129}, issn = {1365-2796}, mesh = {*COVID-19/complications ; Disease Progression ; Hospitalization ; Humans ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease-19 (COVID-19) has resulted in much acute morbidity and mortality worldwide. There is now a growing recognition of the post-acute sequela of COVID-19, termed long COVID. However, the risk factors contributing to this condition remain unclear. Here, we address the growing controversy in the literature of whether hospitalization is a risk factor for long COVID. We found that hospitalization is associated with worse pulmonary restriction and reduction in diffusion capacity at 3 months post-infection. However, the impact on mental health, functional and quality of life is equally severe in those who have and have not been hospitalized during the acute infection. These findings suggest that hospitalization is a risk factor for pulmonary complications of long COVID but not the overall severity of long COVID.}, } @article {pmid34873584, year = {2021}, author = {Canas, LS and Österdahl, MF and Deng, J and Hu, C and Selvachandran, S and Polidori, L and May, A and Molteni, E and Murray, B and Chen, L and Kerfoot, E and Klaser, K and Antonelli, M and Hammers, A and Spector, T and Ourselin, S and Steves, C and Sudre, CH and Modat, M and Duncan, EL}, title = {Disentangling post-vaccination symptoms from early COVID-19.}, journal = {EClinicalMedicine}, volume = {42}, number = {}, pages = {101212}, pmid = {34873584}, issn = {2589-5370}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app.

METHODS: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models considering UK testing criteria.

FINDINGS: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue).

INTERPRETATION: Post-vaccination symptoms per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread.

FUNDING: UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Chronic Disease Research Foundation, Zoe Limited.}, } @article {pmid34872154, year = {2021}, author = {Weingärtner, AL and Stengel, A}, title = {[Fatigue at Long COVID].}, journal = {Psychotherapie, Psychosomatik, medizinische Psychologie}, volume = {71}, number = {12}, pages = {515-527}, doi = {10.1055/a-1544-8349}, pmid = {34872154}, issn = {1439-1058}, mesh = {*COVID-19/complications ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent or new symptoms after infection with SARS-CoV-2 are common and are referred to as Long COVID. Fatigue is by far the most common symptom. The current article deals with fatigue in the context of Long COVID, attempts a pathogenetic classification and makes suggestions for appropriate treatment.}, } @article {pmid34871947, year = {2022}, author = {Steinbeis, F and Thibeault, C and Doellinger, F and Ring, RM and Mittermaier, M and Ruwwe-Glösenkamp, C and Alius, F and Knape, P and Meyer, HJ and Lippert, LJ and Helbig, ET and Grund, D and Temmesfeld-Wollbrück, B and Suttorp, N and Sander, LE and Kurth, F and Penzkofer, T and Witzenrath, M and Zoller, T}, title = {Severity of respiratory failure and computed chest tomography in acute COVID-19 correlates with pulmonary function and respiratory symptoms after infection with SARS-CoV-2: An observational longitudinal study over 12 months.}, journal = {Respiratory medicine}, volume = {191}, number = {}, pages = {106709}, pmid = {34871947}, issn = {1532-3064}, mesh = {Adult ; Aged ; COVID-19/*complications/diagnostic imaging/*physiopathology/therapy ; Extracorporeal Membrane Oxygenation ; Female ; Forced Expiratory Volume/physiology ; Hospitalization ; Humans ; Longitudinal Studies ; Lung/diagnostic imaging/*physiopathology ; Male ; Middle Aged ; Oxygen Inhalation Therapy ; Pulmonary Diffusing Capacity/physiology ; *Quality of Life ; Recovery of Function ; Respiration, Artificial ; Respiratory Function Tests ; Respiratory Insufficiency/diagnostic imaging/*physiopathology/therapy ; SARS-CoV-2 ; Severity of Illness Index ; Surveys and Questionnaires ; Tomography, X-Ray Computed ; Total Lung Capacity/physiology ; Vital Capacity/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19.

METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19.

RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease.

CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.}, } @article {pmid34870392, year = {2021}, author = {Zimmermann, P and Pittet, LF and Curtis, N}, title = {How Common is Long COVID in Children and Adolescents?.}, journal = {The Pediatric infectious disease journal}, volume = {40}, number = {12}, pages = {e482-e487}, pmid = {34870392}, issn = {1532-0987}, mesh = {Adolescent ; COVID-19/*complications/epidemiology/ethnology/*pathology ; Child ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In children, the risk of coronavirus disease (COVID) being severe is low. However, the risk of persistent symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncertain in this age group, and the features of "long COVID" are poorly characterized. We reviewed the 14 studies to date that have reported persistent symptoms following COVID in children and adolescents. Almost all the studies have major limitations, including the lack of a clear case definition, variable follow-up times, inclusion of children without confirmation of SARS-CoV-2 infection, reliance on self- or parent-reported symptoms without clinical assessment, nonresponse and other biases, and the absence of a control group. Of the 5 studies which included children and adolescents without SARS-CoV-2 infection as controls, 2 did not find persistent symptoms to be more prevalent in children and adolescents with evidence of SARS-CoV-2 infection. This highlights that long-term SARS-CoV-2 infection-associated symptoms are difficult to distinguish from pandemic-associated symptoms.}, } @article {pmid34869451, year = {2021}, author = {Hohberger, B and Harrer, T and Mardin, C and Kruse, F and Hoffmanns, J and Rogge, L and Heltmann, F and Moritz, M and Szewczykowski, C and Schottenhamml, J and Kräter, M and Bergua, A and Zenkel, M and Gießl, A and Schlötzer-Schrehardt, U and Lämmer, R and Herrmann, M and Haberland, A and Göttel, P and Müller, J and Wallukat, G}, title = {Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {754667}, pmid = {34869451}, issn = {2296-858X}, abstract = {Clinical features of Coronavirus disease 2019 (COVID-19) are caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial healthcare issue, and the development of long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as impaired capillary microcirculation, chronic fatigue syndrome (CFS), proinflammatory cytokines, and functional autoantibodies targeting G-protein-coupled receptors (GPCR-AAbs). Here, we present a case report of successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with a high affinity to GPCR-AAbs that neutralizes these AAbs. A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from CFS, loss of taste, and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by constant improvement of the fatigue symptoms of the patient, taste, and retinal capillary microcirculation. Therefore, the removal of GPCR-AAb might ameliorate the characteristics of the LCD, such as capillary impairment, loss of taste, and CFS.}, } @article {pmid34868880, year = {2022}, author = {Desai, AD and Boursiquot, BC and Moore, CJ and Gopinathannair, R and Waase, MP and Rubin, GA and Wan, EY}, title = {Autonomic dysfunction post-acute COVID-19 infection.}, journal = {HeartRhythm case reports}, volume = {8}, number = {3}, pages = {143-146}, pmid = {34868880}, issn = {2214-0271}, support = {R01 HL152236/HL/NHLBI NIH HHS/United States ; }, } @article {pmid34868622, year = {2021}, author = {Miyake, E and Martin, S}, title = {Long Covid: Online patient narratives, public health communication and vaccine hesitancy.}, journal = {Digital health}, volume = {7}, number = {}, pages = {20552076211059649}, pmid = {34868622}, issn = {2055-2076}, abstract = {INTRODUCTION: This study combines quantitative and qualitative analyses of social media data collected through three key stages of the pandemic, to highlight the following: 'First wave' (March to May, 2020): negative consequences arising from a disconnect between official health communications, and unofficial Long Covid sufferers' narratives online.'Second wave' (October 2020 to January 2021): closing the 'gap' between official health communications and unofficial patient narratives, leading to a better integration between patient voice, research and services.'Vaccination phase' (January 2021, early stages of the vaccination programme in the UK): continuing and new emerging concerns.

METHODS: We adopted a mixed methods approach involving quantitative and qualitative analyses of 1.38 million posts mentioning long-term symptoms of Covid-19, gathered across social media and news platforms between 1 January 2020 and 1 January 2021, on Twitter, Facebook, Blogs, and Forums. Our inductive thematic analysis was informed by our discourse analysis of words, and sentiment analysis of hashtags and emojis.

RESULTS: Results indicate that the negative impacts arise mostly from conflicting definitions of Covid-19 and fears around the Covid-19 vaccine for Long Covid sufferers. Key areas of concern are: time/duration; symptoms/testing; emotional impact; lack of support and resources.

CONCLUSIONS: Whilst Covid-19 is a global issue, specific sociocultural, political and economic contexts mean patients experience Long Covid at a localised level, needing appropriate localised responses. This can only happen if we build a knowledge base that begins with the patient, ultimately informing treatment and rehabilitation strategies for Long Covid.}, } @article {pmid34867943, year = {2021}, author = {Lim, J and Puan, KJ and Wang, LW and Teng, KWW and Loh, CY and Tan, KP and Carissimo, G and Chan, YH and Poh, CM and Lee, CY and Fong, SW and Yeo, NK and Chee, RS and Amrun, SN and Chang, ZW and Tay, MZ and Torres-Ruesta, A and Leo Fernandez, N and How, W and Andiappan, AK and Lee, W and Duan, K and Tan, SY and Yan, G and Kalimuddin, S and Lye, DC and Leo, YS and Ong, SWX and Young, BE and Renia, L and Ng, LFP and Lee, B and Rötzschke, O}, title = {Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {710217}, pmid = {34867943}, issn = {1664-3224}, mesh = {Adult ; Aged ; COVID-19/complications/*immunology ; Cohort Studies ; Convalescence ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/*immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states.}, } @article {pmid34867791, year = {2021}, author = {Edwards, C and Klekot, O and Halugan, L and Korchev, Y}, title = {Follow Your Nose: A Key Clue to Understanding and Treating COVID-19.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {747744}, pmid = {34867791}, issn = {1664-2392}, mesh = {Adenosine Triphosphate/metabolism ; Adult ; Aged ; Angiopoietin-2/biosynthesis ; Angiotensin-Converting Enzyme 2/biosynthesis ; Animals ; Anosmia/*complications ; COVID-19/blood/*diagnosis/*therapy ; Dexamethasone/administration & dosage/blood/therapeutic use ; Endothelial Cells/metabolism ; Female ; Humans ; Hydrocortisone/metabolism ; Kidney/drug effects ; Male ; Middle Aged ; Models, Biological ; *Nociception ; Polymerase Chain Reaction ; Rats ; Receptors, Mineralocorticoid/biosynthesis ; *SARS-CoV-2 ; Spironolactone/blood ; *Symptom Assessment ; von Willebrand Factor/biosynthesis ; }, abstract = {This paper suggests that ATP release induced by the SARS-CoV-2 virus plays a key role in the genesis of the major symptoms and complications of COVID-19. Infection of specific cells which contain the Angiotensin-Converting Enzyme 2 (ACE2) receptor results in a loss of protection of the Mineralocorticoid Receptor (MR). Local activation by cortisol stimulates the release of ATP initially into the basolateral compartment and then by lysosomal exocytosis from the cell surface. This then acts on adjacent cells. In the nose ATP acts as a nociceptive stimulus which results in anosmia. It is suggested that a similar paracrine mechanism is responsible for the loss of taste. In the lung ATP release from type 2 alveolar cells produces the non-productive cough by acting on purinergic receptors on adjacent neuroepithelial cells and activating, via the vagus, the cough reflex. Infection of endothelial cells results in the exocytosis of WeibelPalade bodies. These contain the Von Willebrand Factor responsible for micro-clotting and angiopoietin-2 which increases vascular permeability and plays a key role in the Acute Respiratory Distress Syndrome. To test this hypothesis this paper reports proof of concept studies in which MR blockade using spironolactone and low dose dexamethasone (SpiDex) was given to PCR-confirmed COVID-19 patients. In 80 patients with moderate to severe respiratory failure 40 were given SpiDex and 40 conventional treatment with high dose dexamethasone (HiDex). There was 1 death in the HiDex group and none in the SpiDex. As judged by clinical, biochemical and radiological parameters there were clear statistically significant benefits of SpiDex in comparison to HiDex. A further 20 outpatients with COVID-19 were given SpiDex. There was no control group and the aim was to demonstrate safety. No adverse effects were noted and no patient became hyperkalaemic. 90% were asymptomatic at 10 days. The very positive results suggest that blockade of the MR can produce major benefit in COVID19 patients. Further larger controlled studies of inpatients and outpatients are required not only for SARS-CoV-2 infection per se but also to determine if this treatment affects the incidence of Long COVID.}, } @article {pmid34865592, year = {2022}, author = {Rao, A and Veluswamy, SK and Shankarappa, BG and Reddy, RM and Umesh, N and John, L and Mathew, L and Shetty, N}, title = {Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study.}, journal = {Expert review of anti-infective therapy}, volume = {20}, number = {5}, pages = {781-787}, pmid = {34865592}, issn = {1744-8336}, mesh = {Adult ; *COVID-19/complications/prevention & control ; COVID-19 Testing ; Female ; Health Personnel ; Humans ; Hydroxychloroquine/adverse effects ; Male ; Pandemics/prevention & control ; *Pre-Exposure Prophylaxis ; Prospective Studies ; SARS-CoV-2 ; Young Adult ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Hydroxychloroquine had attracted significant attention in the initial phases of the COVID-19 pandemic but current recommendations do not support its use. However, the evidence against its use as pre-exposure prophylaxis have been of low to moderate quality and have been limited by high risk of bias.

METHODS: Following institutional ethics committee approval, healthcare workers (n = 1294) completing their first week-long COVID in-patient duty, subsequent institutional quarantine and RT-PCR testing for COVID-19 infection were included for this prospective cohort study. Demographic data, hydroxychloroquine usage and related adverse effects were captured through a 'Caring for the Caregivers' surveillance system. A chi-Square test of independence was used to determine the effect of hydroxychloroquine prophylaxis.

RESULTS: Among the 1294 participants (age: 31 ± 7 years, 61% women), 273 (21.1%) healthcare workers used hydroxychloroquine prophylaxis as per Indian Council of Medical Research recommendations and 83/1294 (6.4%) tested positive after their duty. There was no significant difference in COVID-19 incidence between those on hydroxychloroquine prophylaxis and those not on it (5.9% vs 6.6%, χ[2] = 0.177, p = 0.675; RR = 0.89, 95% CI - 0.53 to 1.52). There were no significant adverse effects to hydroxychloroquine usage.

CONCLUSION: This study demonstrated no benefit of hydroxychloroquine prophylaxis and provides quality evidence against its use in COVID-19 prevention.}, } @article {pmid34863322, year = {2021}, author = {Braz, S}, title = {[Long-COVID: A Challenge for the Medical Community and the National Health Service].}, journal = {Acta medica portuguesa}, volume = {34}, number = {9}, pages = {567-568}, doi = {10.20344/amp.16991}, pmid = {34863322}, issn = {1646-0758}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; *State Medicine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34862223, year = {2021}, author = {Robbins, T and Gonevski, M and Clark, C and Baitule, S and Sharma, K and Magar, A and Patel, K and Sankar, S and Kyrou, I and Ali, A and Randeva, HS}, title = {Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {6}, pages = {e629-e632}, pmid = {34862223}, issn = {1473-4893}, mesh = {Adolescent ; *COVID-19/complications ; Humans ; *Hyperbaric Oxygenation ; Oxygen ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is a common occurrence following COVID-19 infection. The most common symptom reported is fatigue. Limited interventional treatment options exist. We report the first evaluation of hyperbaric oxygen therapy (HBOT) for long COVID treatment.

METHODS: A total of 10 consecutive patients received 10 sessions of HBOT to 2.4 atmospheres over 12 days. Each treatment session lasted 105 minutes, consisting of three 30-minute exposures to 100% oxygen, interspersed with 5-minute air breaks. Validated fatigue and cognitive scoring assessments were performed at day 1 and 10. Statistical analysis was with Wilcoxon signed-rank testing reported alongside effect sizes.

RESULTS: HBOT yielded a statistically significant improvement in the Chalder fatigue scale (p=0.0059; d=1.75 (very large)), global cognition (p=0.0137; d=-1.07 (large)), executive function (p=0.0039; d=-1.06 (large)), attention (p=0.0020; d=-1.2 (very large)), information processing (p=0.0059; d=-1.25 (very large)) and verbal function (p=0.0098; d=-0.92 (large)).

CONCLUSION: Long COVID-related fatigue can be debilitating, and may affect young people who were previously in economic employment. The results presented here suggest potential benefits of HBOT, with statistically significant results following 10 sessions.}, } @article {pmid34861604, year = {2022}, author = {Tleyjeh, IM and Saddik, B and Ramakrishnan, RK and AlSwaidan, N and AlAnazi, A and Alhazmi, D and Aloufi, A and AlSumait, F and Berbari, EF and Halwani, R}, title = {Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up.}, journal = {Journal of infection and public health}, volume = {15}, number = {1}, pages = {21-28}, pmid = {34861604}, issn = {1876-035X}, mesh = {Adolescent ; Adult ; Aftercare ; Aged ; *COVID-19/complications ; Cohort Studies ; *Dyspnea/epidemiology/virology ; *Exercise Tolerance ; *Fatigue Syndrome, Chronic/virology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Patient Discharge ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19.

METHODS: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up.

RESULTS: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score.

CONCLUSIONS: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.}, } @article {pmid34858230, year = {2021}, author = {Bottemanne, H and Gouraud, C and Hulot, JS and Blanchard, A and Ranque, B and Lahlou-Laforêt, K and Limosin, F and Günther, S and Lebeaux, D and Lemogne, C}, title = {Do Anxiety and Depression Predict Persistent Physical Symptoms After a Severe COVID-19 Episode? A Prospective Study.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {757685}, pmid = {34858230}, issn = {1664-0640}, abstract = {Background: Persistent physical symptoms are common after a coronavirus disease 2019 (COVID-19) episode, but their pathophysiological mechanisms remain poorly understood. In this study, we aimed to explore the association between anxiety and depression at 1-month after acute infection and the presence of fatigue, dyspnea, and pain complaints at 3-month follow-up. Methods: We conducted a prospective study in patients previously hospitalized for COVID-19 followed up for 3 months. The Hospital Anxiety and Depression Scale (HAD-S) was administered by physicians at 1-month follow-up, and the presence of fatigue, dyspnea, and pain complaints was assessed at both 1 month and 3 months. Multivariable logistic regressions explored the association between anxiety and depression subscores and the persistence of each of the physical symptom at 3 months. Results: A total of 84 patients were included in this study (Median age: 60 years, interquartile range: 50.5-67.5 years, 23 women). We did not find any significant interaction between anxiety and the presence of fatigue, dyspnea, or pain complaints at 1 month in predicting the persistence of these symptoms at 3 months (all p ≥ 0.36). In contrast, depression significantly interacted with the presence of pain at 1 month in predicting the persistence of pain at 3 months (OR: 1.60, 95% CI: 1.02-2.51, p = 0.039), with a similar trend for dyspnea (OR: 1.51, 95% CI: 0.99-2.28, p = 0.052). Discussion and Conclusion: Contrary to anxiety, depression after an acute COVID-19 episode may be associated with and increased risk of some persistent physical symptoms, including pain and dyspnea.}, } @article {pmid34857243, year = {2021}, author = {Rossato, MS and Brilli, E and Ferri, N and Giordano, G and Tarantino, G}, title = {Observational study on the benefit of a nutritional supplement, supporting immune function and energy metabolism, on chronic fatigue associated with the SARS-CoV-2 post-infection progress.}, journal = {Clinical nutrition ESPEN}, volume = {46}, number = {}, pages = {510-518}, pmid = {34857243}, issn = {2405-4577}, mesh = {*COVID-19 ; Dietary Supplements ; Energy Metabolism ; *Fatigue Syndrome, Chronic ; Humans ; Immunity ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND & AIMS: Recent studies have verified that the SARS-CoV-2 infection (from December 2019 has affected 123 million people throughout the world and more than 3 million people in Italy), can have medium-term and long-term effects, collectively referred to as "post-Covid syndrome" or "long-Covid" characterized by chronic fatigue, followed by muscle weakness, dyspnea and headache. Chronic fatigue or chronic tiredness is a persistent symptom both in patients who have experienced a severe infection and in those who have experienced a mild form of infection. Studies conducted on both patients discharged from hospital and patients managed at home showed that there was no association between the severity of the Coronavirus disease (Covid-19) and the subsequent chronic fatigue symptom. The aim of this study was to evaluate the ability of a nutritional supplement based on vitamins, minerals, amino acids and plant extracts (Apportal®) intake, to ameliorate the general health status in particular the chronic fatigue symptom in subjects after SARS-CoV-2 negativity.

METHODS: Participants were advised to take one sachet daily of Apportal® for 28 consecutive days. At the beginning (T0), after 14 days (T1) and after 28 days (T2) of supplementation, general fatigue, mental fatigue and Quality of Life indexes were evaluated through specific questionnaires. The assessment of quality of life and health status were measured through the EuroQoL-5D questionnaire, chronic fatigue using the FACIT-Fatigue questionnaire and mental fatigue using the modified Chalder questionnaire.

RESULTS: 201 subjects were enrolled for the study; results showed a significant improvement in all indexes analyzed after 14 and 28 days of supplementation. The main significant improvement was observed after the first 14 days and it was further confirmed at 28 days as well. The RTE (Relative Treatment Effect) trend about quality of life, health status, FACIT-Fatigue and mental fatigue in the three questionnaires was statistically significant (Wald Statistic, p < 0.0001). The data of FACIT-questionnaire showed an improvement of at least 1 unit in 76.62% of subjects after 14 days and in 90.05% of subjects after 28 days. An improvement of 10-unit was found in about one third of subjects after 14 days and in half of the subjects after 28 days.

CONCLUSIONS: This study shows that Apportal® can reduce chronic fatigue and improve quality of life and health status in subjects after SARS-CoV-2 negativity due to the synergistic effect of its components.}, } @article {pmid34857010, year = {2021}, author = {Kuut, TA and Müller, F and Aldenkamp, A and Assmann-Schuilwerve, E and Braamse, A and Geerlings, SE and Gibney, KB and Kanaan, RAA and Nieuwkerk, P and Olde Hartman, TC and Pauëlsen, D and Prins, M and Slieker, K and Van Vugt, M and Bleeker-Rovers, CP and Keijmel, SP and Knoop, H}, title = {A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.}, journal = {Trials}, volume = {22}, number = {1}, pages = {867}, pmid = {34857010}, issn = {1745-6215}, support = {10430012010025/ZONMW_/ZonMw/Netherlands ; }, mesh = {*COVID-19/complications ; *Cognitive Behavioral Therapy ; Fatigue/diagnosis/etiology/therapy ; Humans ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2.

METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2.

DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms.

TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.}, } @article {pmid34855874, year = {2021}, author = {Martin, C and Luteijn, M and Letton, W and Robertson, J and McDonald, S}, title = {A model framework for projecting the prevalence and impact of Long-COVID in the UK.}, journal = {PloS one}, volume = {16}, number = {12}, pages = {e0260843}, pmid = {34855874}, issn = {1932-6203}, mesh = {COVID-19/*complications/epidemiology/etiology ; Forecasting ; Humans ; Models, Statistical ; Prevalence ; Quality-Adjusted Life Years ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 disease in the UK population, including symptoms of 'long-COVID'. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long-COVID. The prevalence of symptomatic COVID-19, encompassing acute symptoms and long-COVID symptoms, was modelled using a decay function. Permanent injury as a result of COVID-19 infection, was modelled as a fixed prevalence. Both parts were combined to calculate QALY loss due to COVID-19 symptoms. Assuming a 60% final attack rate for SARS-CoV-2 infection in the population, we modelled 299,730 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,764 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury). The UK Government willingness-to-pay to avoid these QALY losses would be £17.9 billion and £32.2 billion, respectively. Additionally, 90,143 people were subject to permanent injury from COVID-19 (0.14% of the population). Given the ongoing development in information in this area, we present a model framework for calculating the health economic impacts of symptoms following SARS-CoV-2 infection. This model framework can aid in quantifying the adverse health impact of COVID-19, long-COVID and permanent injury following COVID-19 in society and assist the proactive management of risk posed to health. Further research is needed using standardised measures of patient reported outcomes relevant to long-COVID and applied at a population level.}, } @article {pmid34853850, year = {2021}, author = {Ladani, AP and Loganathan, M and Kolikonda, MK and Lippmann, S}, title = {COVID-19 Legacy.}, journal = {Southern medical journal}, volume = {114}, number = {12}, pages = {751-759}, pmid = {34853850}, issn = {1541-8243}, mesh = {COVID-19/*complications/*epidemiology ; Comorbidity ; Humans ; Incidence ; Pandemics ; Prognosis ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infection caused by the severe acute respiratory syndrome-coronavirus-2 virus that led to a pandemic. Acute manifestations of COVID-19 include fever, cough, dyspnea, respiratory failure, pneumonitis, anosmia, thromboembolic events, cardiogenic shock, renal injury, ischemic strokes, encephalitis, and cutaneous eruptions, especially of hands or feet. Prolonged symptoms, unpredictable recoveries, and chronic sequelae (long COVID) sometimes emerge even for some people who survive the initial illness. Sequelae such as fatigue occasionally persist even for those with only mild to moderate cases. There is much to learn about postacute COVID-19 dyspnea, anosmia, psychosis, thyroiditis, cardiac arrhythmia, and/or multisystem inflammatory response syndrome in children. Determining prognoses is imprecise. Examining patient databases about those who have survived COVID-19 is warranted. Multidisciplinary teams are assessing such disease databases to better understand longer-term complications and guide treatment.}, } @article {pmid34853527, year = {2021}, author = {Murugan, AK and Alzahrani, AS}, title = {SARS-CoV-2: Emerging Role in the Pathogenesis of Various Thyroid Diseases.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6191-6221}, pmid = {34853527}, issn = {1178-7031}, abstract = {Coronavirus disease-2019 (COVID-19) is asymptomatic in most cases, but it is impartible and fatal in fragile and elderly people. Heretofore, more than four million people succumbed to COVID-19, while it spreads to every part of the globe. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) induces various dysfunctions in many vital organs including the thyroid by utilizing ACE2 as a receptor for cellular entry. Emerging reports clearly show the involvement of SARS-CoV-2 in diverse thyroid disorders. Thus, this review article aims to review comprehensively all the recent developments in SARS-CoV-2-induced pathogenesis of thyroid diseases. The review briefly summarizes the recent key findings on the mechanism of SARS-CoV-2 infection, the role of ACE2 receptor in viral entry, SARS-CoV-2-activated molecular signaling in host cells, ACE2 expression in the thyroid, cytokine storm, and its vital role in thyroid dysfunction and long-COVID in relation to thyroid and autoimmunity. Further, it extensively discusses rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various thyroid dysfunctions during and post-COVID-19 conditions which include subacute thyroiditis, Graves' diseases, Hashimoto's thyroiditis, thyrotoxicosis, and other recent advances in further discerning the implications of this virus within thyroid dysfunction. Unraveling the pathophysiology of SARS-CoV-2-triggered thyroid dysfunctions may aid pertinent therapeutic options and management of these patients in both during and post-COVID-19 scenarios.}, } @article {pmid34852145, year = {2021}, author = {Fink, TT and Marques, HHS and Gualano, B and Lindoso, L and Bain, V and Astley, C and Martins, F and Matheus, D and Matsuo, OM and Suguita, P and Trindade, V and Paula, CSY and Farhat, SCL and Palmeira, P and Leal, GN and Suzuki, L and Odone Filho, V and Carneiro-Sampaio, M and Duarte, AJS and Antonangelo, L and Batisttella, LR and Polanczyk, GV and Pereira, RMR and Carvalho, CRR and Buchpiguel, CA and Xavier, ACL and Seelaender, M and Silva, CA and Pereira, MFB and , and Sallum, AME and Brentani, AVM and Neto, ÁJS and Ihara, A and Santos, AR and Canton, APM and Watanabe, A and Santos, ACD and Pastorino, AC and Franco, BDGM and Caruzo, B and Ceneviva, C and Martins, CCMF and Prado, D and Abellan, DM and Benatti, FB and Smaria, F and Gonçalves, FT and Penteado, FD and Castro, GSF and Gonçalves, GS and Roschel, H and Disi, IR and Marques, IG and Castro, IA and Buscatti, IM and Faiad, JZ and Fiamoncini, J and Rodrigues, JC and Carneiro, JDA and Paz, JA and Ferreira, JC and Ferreira, JCO and Silva, KR and Bastos, KLM and Kozu, K and Cristofani, LM and Souza, LVB and Campos, LMA and Silva Filho, LVRF and Sapienza, MT and Lima, MS and Garanito, MP and Santos, MFA and Dorna, MB and Aikawa, NE and Litvinov, N and Sakita, NK and Gaiolla, PVV and Pasqualucci, P and Toma, RK and Correa-Silva, S and Sieczkowska, SM and Imamura, M and Forsait, S and Santos, VA and Zheng, Y}, title = {Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.}, journal = {Clinics (Sao Paulo, Brazil)}, volume = {76}, number = {}, pages = {e3511}, pmid = {34852145}, issn = {1980-5322}, mesh = {Adolescent ; *COVID-19/complications ; COVID-19 Testing ; Child ; Humans ; Latin America ; Male ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; Tertiary Care Centers ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19).

METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed.

RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls.

CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.}, } @article {pmid34851455, year = {2021}, author = {Rabady, S and Altenberger, J and Brose, M and Denk-Linnert, DM and Fertl, E and Götzinger, F and de la Cruz Gomez Pellin, M and Hofbaur, B and Hoffmann, K and Hoffmann-Dorninger, R and Koczulla, R and Lammel, O and Lamprecht, B and Löffler-Ragg, J and Müller, CA and Poggenburg, S and Rittmannsberger, H and Sator, P and Strenger, V and Vonbank, K and Wancata, J and Weber, T and Weber, J and Weiss, G and Wendler, M and Zwick, RH}, title = {[Guideline S1: Long COVID: Diagnostics and treatment strategies].}, journal = {Wiener klinische Wochenschrift}, volume = {133}, number = {Suppl 7}, pages = {237-278}, pmid = {34851455}, issn = {1613-7671}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV‑2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.}, } @article {pmid34850782, year = {2021}, author = {Marciniak, E and Górniak, A and Hanke, W}, title = {[Long lasting symptoms of dyspnea, cough and fatigue after COVID-19 - narrative review of epidemiological studies].}, journal = {Medycyna pracy}, volume = {72}, number = {6}, pages = {711-720}, doi = {10.13075/mp.5893.01190}, pmid = {34850782}, issn = {2353-1339}, mesh = {*COVID-19/complications ; Cough/epidemiology/etiology ; Dyspnea/epidemiology ; Epidemiologic Studies ; Humans ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {"Long-COVID" is described as long-term effects of SARS‑ CoV‑2 infection that last >4 weeks after the acutephase of infection. The aim of this narrative reviews to evaluate the frequency of occurrence of 3 symptoms often observed in Long-COVID, i.e., chronic fatigue, shortness of breath and cough, and whether comorbidities such as diabetes and arterial hypertension increase the risk of complications after a history of SARS‑ CoV‑2 infection. The method of narrative review was used in this paper. PubMed (May 31, 2021) search was performed to retrieve articles concerning the occurrence of long COVID-19 chronic fatigue, dyspnoea and chronic cough. Studies in which the observation period was <30 days and the average age of subjects exceeded 60 years, as well as studies with no information on the methodology used, in particular without the method of recruiting people for the study, were excluded. Populations with a high frequency of diabetes were defined as the prevalence >10%, and in the case of arterial hypertension >40%. The average frequency of diabetes <10%, hypertension 40%. It can be concluded that in the period of >30 days after discharge from the hospital, in populations with a high incidence of diabetes and hypertension, the incidence of chronic fatigue and cough was higher than in the other analyzed groups. Symptoms of dyspnea were most frequently reported in populations with high rates of diabetes, but at the same time in the average percentage of people with arterial hypertension. Persistent symptoms specific to "Long-COVID" can significantly reduce the ability to perform work. In this situation, check-ups performed before returning to work after long-term leave tape on a new dimension. Med Pr. 2021;72(6):711-20.}, } @article {pmid34850268, year = {2021}, author = {Steinestel, K and Czech, A and Hackenbroch, C and Bloch, W and Gagiannis, D}, title = {[Clinical, radiological, and histopathological features of pulmonary post-COVID syndrome : A form of autoimmune-mediated interstitial lung disease?].}, journal = {Der Pathologe}, volume = {42}, number = {Suppl 2}, pages = {160-164}, pmid = {34850268}, issn = {1432-1963}, mesh = {Adult ; *COVID-19 ; Humans ; Lung/diagnostic imaging ; *Lung Diseases, Interstitial ; Pilot Projects ; SARS-CoV-2 ; }, abstract = {BACKGROUND: About 10% of patients develop persistent symptoms after mild/moderate COVID-19. We have previously reported detection of antinuclear autoantibodies/extractable nuclear antigens (ANA/ENA) in patients with severe COVID-19.

OBJECTIVES: The aim of this small pilot study was to characterize long-/post-COVID and to evaluate possible similarities between lung involvement in long-/post-COVID and connective tissue disease (CTD).

METHODS: We prospectively enrolled 33 previously healthy patients with persistent pulmonal symptoms after mild/moderate COVID-19 without hospitalization (median age, 39 years). We performed clinical evaluation including pulmonary function tests, computed tomography (CT), and serology for ANA/ENA. In 29 of 33 patients, transbronchial biopsies (TBBs) were taken for histopathological assessment.

RESULTS: Most patients presented with disturbed oxygen pulse in spiroergometry and slight lymphocytosis in bronchoalveolar lavage (BAL) fluid. The CT pattern showed bronchial wall thickening and increased low-attenuation volume. Autoantibodies were detected in 13 of 33 patients (39.4%). Histopathological assessment showed interstitial lymphocytosis with alveolar fibrin and organizing pneumonia. Ultrastructural analyses revealed interstitial collagen deposition.

CONCLUSION: While histopathology of pulmonary long-/post-COVID alone is unspecific, the combination with clinical and radiological features together with detection of autoantibodies would allow for a diagnosis of interstitial pneumonia with autoimmune features (IPAF). Since we observe interstitial collagen deposition and since IPAF/CTD-ILD might progress to fibrosis, the persistence of autoantibodies and possible fibrotic change should be closely monitored in autoantibody-positive long-/post-COVID patients.}, } @article {pmid34850227, year = {2022}, author = {Kelly, BD and Gulati, G}, title = {Long COVID: the elephant in the room.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {115}, number = {1}, pages = {5-6}, pmid = {34850227}, issn = {1460-2393}, mesh = {*Aortic Aneurysm, Thoracic ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34850210, year = {2022}, author = {Boglione, L and Meli, G and Poletti, F and Rostagno, R and Moglia, R and Cantone, M and Esposito, M and Scianguetta, C and Domenicale, B and Di Pasquale, F and Borrè, S}, title = {Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {114}, number = {12}, pages = {865-871}, pmid = {34850210}, issn = {1460-2393}, mesh = {Adenosine Monophosphate/analogs & derivatives/*therapeutic use ; Alanine/analogs & derivatives/*therapeutic use ; *COVID-19/complications ; Hospitalization ; Humans ; Incidence ; Intensive Care Units ; Prospective Studies ; Risk Factors ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The definition of 'long-COVID syndrome' (LCS) is still debated and describes the persistence of symptoms after viral clearance in hospitalized or non-hospitalized patients affected by coronavirus disease 2019 (COVID-19).

AIM: In this study, we examined the prevalence and the risk factors of LCS in a cohort of patients with previous COVID-19 and followed for at least 6 months of follow-up.

DESIGN: We conducted a prospective study including all hospitalized patients affected by COVID-19 at our center of Infectious Diseases (Vercelli, Italy) admitted between 10 March 2020 and 15 January 2021 for at least 6 months after discharge. Two follow-up visits were performed: after 1 and 6 months after hospital discharge. Clinical, laboratory and radiological data were recorded at each visit.

RESULTS: A total of 449 patients were included in the analysis. The LCS was diagnosed in 322 subjects at Visit 1 (71.7%) and in 206 at Visit 2 (45.9); according to the post-COVID-19 functional status scale we observed 147 patients with values 2-3 and 175 with values >3 at Visit 1; at Visit 2, 133 subjects had the score between 2-3 and 73 > 3. In multivariate analysis, intensive care unit (ICU) admission (OR = 2.551; 95% CI = 1.998-6.819; P = 0.019), time of hospitalization (OR = 2.255; 95% CI = 1.018-6.992; P = 0.016) and treatment with remdesivir (OR = 0.641; 95% CI = 0.413-0.782; P < 0.001) were independent predictors of LCS.

CONCLUSIONS: Treatment with remdesivir leads to a 35.9% reduction in LCS rate in follow-up. Severity of illness, need of ICU admission and length of hospital stay were factor associated with the persistence of PCS at 6 months of follow-up.}, } @article {pmid34849658, year = {2022}, author = {Zavala, M and Ireland, G and Amin-Chowdhury, Z and Ramsay, ME and Ladhani, SN}, title = {Acute and Persistent Symptoms in Children With Polymerase Chain Reaction (PCR)-Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Compared With Test-Negative Children in England: Active, Prospective, National Surveillance.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {1}, pages = {e191-e200}, doi = {10.1093/cid/ciab991}, pmid = {34849658}, issn = {1537-6591}, mesh = {*COVID-19/diagnosis/epidemiology ; COVID-19 Testing ; Child ; Fever ; Humans ; Polymerase Chain Reaction ; Prospective Studies ; *SARS-CoV-2/genetics ; }, abstract = {BACKGROUND: Most children recover quickly after coronavirus disease 2019 (COVID-19), but some may have ongoing symptoms. Follow-up studies have been limited by small sample sizes and lack of appropriate controls.

METHODS: We used national testing data to identify children aged 2-16 years with a SARS-CoV-2 PCR test during 1-7 January 2021 and randomly selected 1500 PCR-positive cases and 1500 matched PCR-negative controls. Parents were asked to complete a questionnaire about the acute illness and prespecified neurological, dermatological, sensory, respiratory, cardiovascular, gastrointestinal, mental health (including emotional and behavioral well-being), and other symptoms experienced ≥5 times at 1 month after the PCR test.

RESULTS: Overall, 35.0% (859/2456) completed the questionnaire, including 38.0% (472/1242) of cases and 32% (387/1214) of controls, of whom 68% (320/472) and 40% (154/387) were symptomatic, respectively. The most prevalent acute symptoms were cough (249/859, 29.0%), fever (236/859, 27.5%), headache (236/859, 27.4%), and fatigue (231/859, 26.9%). One month later, 21/320 (6.7%) of symptomatic cases and 6/154 (4.2%) of symptomatic controls (P = .24) experienced ongoing symptoms. Of the 65 ongoing symptoms solicited, 3 clusters were significantly (P < .05) more common, albeit at low prevalence, among symptomatic cases (3-7%) than symptomatic controls (0-3%): neurological, sensory, and emotional and behavioral well-being. Mental health symptoms were reported by all groups but more frequently among symptomatic cases than symptomatic controls or asymptomatic children.

CONCLUSIONS: Children with symptomatic COVID-19 had a slightly higher prevalence of ongoing symptoms than symptomatic controls, and not as high as previously reported. Healthcare resources should be prioritized to support the mental health of children.}, } @article {pmid34849652, year = {2022}, author = {Sahanic, S and Tymoszuk, P and Ausserhofer, D and Rass, V and Pizzini, A and Nordmeyer, G and Hüfner, K and Kurz, K and Weber, PM and Sonnweber, T and Boehm, A and Aichner, M and Cima, K and Boeckle, B and Holzner, B and Rumpold, G and Puelacher, C and Kiechl, S and Huber, A and Wiedermann, CJ and Sperner-Unterweger, B and Tancevski, I and Bellmann-Weiler, R and Bachler, H and Piccoliori, G and Helbok, R and Weiss, G and Loeffler-Ragg, J}, title = {Phenotyping of Acute and Persistent Coronavirus Disease 2019 Features in the Outpatient Setting: Exploratory Analysis of an International Cross-sectional Online Survey.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {1}, pages = {e418-e431}, doi = {10.1093/cid/ciab978}, pmid = {34849652}, issn = {1537-6591}, mesh = {*COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Outpatients ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID, defined as the presence of coronavirus disease 2019 (COVID-19) symptoms ≥28 days after clinical onset, is an emerging challenge to healthcare systems. The objective of the current study was to explore recovery phenotypes in nonhospitalized individuals with COVID-19.

METHODS: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY; Austria, n = 1157) and South Tyrol (STY; Italy, n = 893). Data were collected on demographics, comorbid conditions, COVID-19 symptoms, and recovery in adult outpatients. Phenotypes of acute COVID-19, postacute sequelae, and risk of protracted recovery were explored using semi-supervised clustering and multiparameter least absolute shrinkage and selection operator (LASSO) modeling.

RESULTS: Participants in the study cohorts were predominantly working age (median age [interquartile range], 43 [31-53] years] for TY and 45 [35-55] years] for STY) and female (65.1% in TY and 68.3% in STY). Nearly half (47.6% in TY and 49.3% in STY) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the nonspecific infection phenotype and the multiorgan phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal, and dermatological symptoms were linked to elevated risk of protracted recovery. The major subset of individuals with long COVID (49.3% in TY; 55.6% in STY) displayed no persistent hyposmia or hypogeusia but high counts of postacute MOP symptoms and poor self-reported physical recovery.

CONCLUSIONS: The results of our 2-cohort analysis delineated phenotypic diversity of acute and postacute COVID-19 manifestations in home-isolated patients, which must be considered in predicting protracted convalescence and allocating medical resources.}, } @article {pmid34848509, year = {2021}, author = {Genecand, C and Mongin, D and Koegler, F and Lebowitz, D and Regard, S and Falcone, JL and Nehme, M and Braillard, O and Grira, M and Joubert, D and Chopard, P and Delaporte, E and Stirnemann, J and Guessous, I and Tardin, A and Courvoisier, DS}, title = {Cohort profile: Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS).}, journal = {BMJ open}, volume = {11}, number = {11}, pages = {e048946}, pmid = {34848509}, issn = {2044-6055}, mesh = {*COVID-19/complications ; Humans ; Inpatients ; Outpatients ; Pandemics ; Prospective Studies ; Retrospective Studies ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: The Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS) is an ongoing prospective cohort created by the Geneva Directorate of Health. It consists of an operational database compiling all SARS-CoV-2 test results recorded in the Geneva area since late February 2020. This article aims at presenting this comprehensive cohort, in light of some of the varying public health measures in Geneva, Switzerland, since March 2020.

PARTICIPANTS: As of 1 June 2021, the database included 360 525 patients, among which 65 475 had at least one positive test result for SARS-CoV-2. Among all positive patients, 37.6% were contacted only once, 10.6% had one follow-up call, 8.5% had two and 27.7% had three or more follow-up calls. Participation rate among positive patients is 94%. Data collection is ongoing.

FINDINGS TO DATE: ARGOS data illustrates the magnitude of COVID-19 pandemic in Geneva, Switzerland, and details a variety of population factors and outcomes. The content of the cohort includes demographic data, comorbidities and risk factors for poor clinical outcome, self-reported COVID-19 symptoms, environmental and socioeconomic factors, prospective and retrospective contact tracing data, travel quarantine data and deaths. The registry has already been used in several publications focusing on symptoms and long COVID-19, infection fatality rate and re-infection.

FUTURE PLANS: The data of this large real-world registry provides a valuable resource for various types of research, such as clinical research, epidemiological research or policy assessment as it illustrates the impact of public health policies and overall disease burden of COVID-19.}, } @article {pmid34848374, year = {2022}, author = {Nguyen, NN and Hoang, VT and Dao, TL and Meddeb, L and Lagier, JC and Million, M and Raoult, D and Gautret, P}, title = {Long-term persistence of symptoms of dyspnoea in COVID-19 patients.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {115}, number = {}, pages = {17-23}, pmid = {34848374}, issn = {1878-3511}, mesh = {*COVID-19 ; Dyspnea/etiology ; Humans ; SARS-CoV-2 ; }, } @article {pmid34845562, year = {2022}, author = {Sapkota, HR and Nune, A}, title = {Long COVID from rheumatology perspective - a narrative review.}, journal = {Clinical rheumatology}, volume = {41}, number = {2}, pages = {337-348}, pmid = {34845562}, issn = {1434-9949}, mesh = {*COVID-19/complications ; Humans ; *Rheumatic Diseases/complications/diagnosis ; *Rheumatology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term sequel of acute COVID-19, commonly referred to as long COVID, has affected millions of patients worldwide. Long COVID patients display persistent or relapsing and remitting symptoms that include fatigue, breathlessness, cough, myalgia, arthralgia, sleep disturbance, cognitive impairment and skin rashes. Due to the shared clinical features, laboratory and imaging findings, long COVID could mimic rheumatic disease posing a diagnostic challenge. Our comprehensive literature review will help rheumatologist to be aware of long COVID manifestations and differentiating features from rheumatic diseases to ensure a timely and correct diagnosis is reached.}, } @article {pmid34845462, year = {2022}, author = {Hafiz, R and Gandhi, TK and Mishra, S and Prasad, A and Mahajan, V and Di, X and Natelson, BH and Biswal, BB}, title = {Higher Limbic and Basal Ganglia volumes in surviving COVID-negative patients and the relations to fatigue.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {34845462}, support = {R01 AT009829/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND: Among systemic abnormalities caused by the novel coronavirus, little is known about the critical attack on the central nervous system (CNS). Few studies have shown cerebrovascular pathologies that indicate CNS involvement in acute patients. However, replication studies are necessary to verify if these effects persist in COVID-19 survivors more conclusively. Furthermore, recent studies indicate fatigue is highly prevalent among 'long-COVID' patients. How morphometry in each group relate to work-related fatigue need to be investigated.

METHOD: COVID survivors were MRI scanned two weeks after hospital discharge. We hypothesized, these survivors will demonstrate altered gray matter volume (GMV) and experience higher fatigue levels when compared to healthy controls, leading to stronger correlation of GMV with fatigue. Voxel-based morphometry was performed on T1-weighted MRI images between 46 survivors and 30 controls. Unpaired two-sample t-test and multiple linear regression were performed to observe group differences and correlation of fatigue with GMV.

RESULTS: The COVID group experienced significantly higher fatigue levels and GMV of this group was significantly higher within the Limbic System and Basal Ganglia when compared to healthy controls. Moreover, while a significant positive correlation was observed across the whole group between GMV and self-reported fatigue, COVID subjects showed stronger effects within the Posterior Cingulate, Precuneus and Superior Parietal Lobule .

CONCLUSION: Brain regions with GMV alterations in our analysis align with both single case acute patient reports and current group level neuroimaging findings. We also newly report a stronger positive correlation of GMV with fatigue among COVID survivors within brain regions associated with fatigue, indicating a link between structural abnormality and brain function in this cohort.}, } @article {pmid34842325, year = {2022}, author = {Hunter, P}, title = {Viral diseases and the brain: Long COVID puts the spotlight on how viral infections affect the brain: Long COVID puts the spotlight on how viral infections affect the brain.}, journal = {EMBO reports}, volume = {23}, number = {1}, pages = {e54342}, pmid = {34842325}, issn = {1469-3178}, mesh = {Brain/*virology ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Various viruses can affect the brain directly or indirectly. The specter of Long COVID has focused research on how respiratory viruses can cause infection and inflammation of brain cells.}, } @article {pmid34840383, year = {2021}, author = {Asadi-Pooya, AA and Akbari, A and Emami, A and Lotfi, M and Rostamihosseinkhani, M and Nemati, H and Barzegar, Z and Kabiri, M and Zeraatpisheh, Z and Farjoud-Kouhanjani, M and Jafari, A and Sasannia, F and Ashrafi, S and Nazeri, M and Nasiri, S and Shahisavandi, M}, title = {Risk Factors Associated with Long COVID Syndrome: A Retrospective Study.}, journal = {Iranian journal of medical sciences}, volume = {46}, number = {6}, pages = {428-436}, pmid = {34840383}, issn = {1735-3688}, mesh = {Adult ; COVID-19/*complications/epidemiology ; Female ; Humans ; Iran/epidemiology ; Male ; Retrospective Studies ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Recently, people have recognized the post-acute phase symptoms of the COVID-19. We investigated the long-term symptoms associated with COVID-19, (Long COVID Syndrome), and the risk factors associated with it.

METHODS: This was a retrospective observational study. All the consecutive adult patients referred to the healthcare facilities anywhere in Fars province from 19 February 2020 until 20 November 2020 were included. All the patients had a confirmed COVID-19 diagnosis. In a phone call to the patients, at least three months after their discharge from the hospital, we obtained their current information. The IBM SPSS Statistics (version 25.0) was used. Pearson Chi square, Fisher's exact test, t test, and binary logistic regression analysis model were employed. A P value of less than 0.05 was considered to be significant.

RESULTS: In total, 4,681 patients were studied, 2915 of whom (62.3%) reported symptoms. The most common symptoms of long COVID syndrome were fatigue, exercise intolerance, walking intolerance, muscle pain, and shortness of breath. Women were more likely to experience long-term COVID syndrome than men (Odds Ratio: 1,268; 95% Confidence Interval: 1,122-1,432; P=0.0001), which was significant. Presentation with respiratory problems at the onset of illness was also significantly associated with long COVID syndrome (Odds Ratio: 1.425; 95% Confidence Interval: 1.177-1.724; P=0.0001). A shorter length of hospital stay was inversely associated with long COVID syndrome (Odds Ratio: 0.953; 95% Confidence Interval: 0.941-0.965; P=0.0001).

CONCLUSION: Long COVID syndrome is a frequent and disabling condition and has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness.}, } @article {pmid34840031, year = {2022}, author = {Raghavan, K and Dedeepiya, VD and Suryaprakash, V and Rao, KS and Ikewaki, N and Sonoda, T and Levy, GA and Iwasaki, M and Senthilkumar, R and Preethy, S and Abraham, SJ}, title = {Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {145}, number = {}, pages = {112243}, pmid = {34840031}, issn = {1950-6007}, mesh = {*Aureobasidium ; Biomarkers/blood ; *COVID-19/blood/diagnosis ; Complementary Therapies/methods ; *Cytokine Release Syndrome/blood/etiology/prevention & control ; Dietary Supplements ; Female ; Fibrin Fibrinogen Degradation Products/*analysis ; Humans ; Immunologic Factors/administration & dosage ; Interleukin-6/*analysis ; Male ; Middle Aged ; Pilot Projects ; SARS-CoV-2 ; Treatment Outcome ; beta-Glucans/*administration & dosage ; *COVID-19 Drug Treatment ; }, abstract = {OBJECTIVE: In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients.

METHODS: A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n = 8) - Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n = 8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n = 8) for 30 days.

RESULTS: There was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395-3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18-3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25-0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4 + and CD8 + T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups.

CONCLUSION: As these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.}, } @article {pmid34839808, year = {2022}, author = {Benzarti, W and Toulgui, E and Prefaut, C and Chamari, K and Ben Saad, H}, title = {General practitioners should provide the cardiorespiratory rehabilitation' 'minimum advice' for long COVID-19 patients.}, journal = {The Libyan journal of medicine}, volume = {17}, number = {1}, pages = {2009101}, pmid = {34839808}, issn = {1819-6357}, mesh = {*COVID-19/complications ; *General Practitioners ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34839684, year = {2021}, author = {Nguyen-Hoang, A}, title = {Nutrition therapy for long COVID.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {30}, number = {21}, pages = {S28-S29}, doi = {10.12968/bjon.2021.30.21.S28}, pmid = {34839684}, issn = {2052-2819}, mesh = {*COVID-19/complications ; Humans ; *Nutrition Therapy ; Nutritional Status ; Nutritional Support ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34839263, year = {2021}, author = {Deer, RR and Rock, MA and Vasilevsky, N and Carmody, L and Rando, H and Anzalone, AJ and Basson, MD and Bennett, TD and Bergquist, T and Boudreau, EA and Bramante, CT and Byrd, JB and Callahan, TJ and Chan, LE and Chu, H and Chute, CG and Coleman, BD and Davis, HE and Gagnier, J and Greene, CS and Hillegass, WB and Kavuluru, R and Kimble, WD and Koraishy, FM and Köhler, S and Liang, C and Liu, F and Liu, H and Madhira, V and Madlock-Brown, CR and Matentzoglu, N and Mazzotti, DR and McMurry, JA and McNair, DS and Moffitt, RA and Monteith, TS and Parker, AM and Perry, MA and Pfaff, E and Reese, JT and Saltz, J and Schuff, RA and Solomonides, AE and Solway, J and Spratt, H and Stein, GS and Sule, AA and Topaloglu, U and Vavougios, GD and Wang, L and Haendel, MA and Robinson, PN}, title = {Characterizing Long COVID: Deep Phenotype of a Complex Condition.}, journal = {EBioMedicine}, volume = {74}, number = {}, pages = {103722}, pmid = {34839263}, issn = {2352-3964}, support = {K23 DK124654/DK/NIDDK NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; R01 HG010067/HG/NHGRI NIH HHS/United States ; K23 HL128909/HL/NHLBI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; K99 GM145411/GM/NIGMS NIH HHS/United States ; P30 AG024832/AG/NIA NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; }, mesh = {COVID-19/*complications/diagnosis/*pathology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.

METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19.

FUNDING: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies.

INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID.

FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.}, } @article {pmid34838682, year = {2022}, author = {Seitz, A and Ong, P}, title = {Endothelial dysfunction in COVID-19: A potential predictor of long-COVID?.}, journal = {International journal of cardiology}, volume = {349}, number = {}, pages = {155-156}, pmid = {34838682}, issn = {1874-1754}, mesh = {*COVID-19/complications ; Endothelium, Vascular ; Humans ; SARS-CoV-2 ; *Vascular Diseases ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34836878, year = {2021}, author = {Van de Vyver, J and Leite, AC and Alwan, NA}, title = {Navigating the social identity of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {375}, number = {}, pages = {n2933}, doi = {10.1136/bmj.n2933}, pmid = {34836878}, issn = {1756-1833}, mesh = {Adult ; Avoidance Learning ; Biomedical Research/*methods ; COVID-19/*complications/diagnosis/epidemiology/physiopathology/psychology/virology ; Child ; Female ; Help-Seeking Behavior ; Humans ; Interdisciplinary Research/methods ; Prevalence ; Quality of Life ; SARS-CoV-2/genetics ; Social Identification ; Social Isolation/*psychology ; Social Stigma ; United Kingdom/epidemiology ; Vulnerable Populations/psychology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34836219, year = {2021}, author = {Gérard, M and Mahmutovic, M and Malgras, A and Michot, N and Scheyer, N and Jaussaud, R and Nguyen-Thi, PL and Quilliot, D}, title = {Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19.}, journal = {Nutrients}, volume = {13}, number = {11}, pages = {}, pmid = {34836219}, issn = {2072-6643}, mesh = {Adult ; Aged ; COVID-19/*complications/diagnosis/physiopathology/therapy ; Female ; Functional Status ; Hospitalization ; Humans ; Length of Stay ; Male ; Malnutrition/diagnosis/*etiology/physiopathology/therapy ; Middle Aged ; *Muscle Strength ; Muscle Weakness/diagnosis/*etiology/physiopathology/therapy ; Muscle, Skeletal/*physiopathology ; *Nutritional Status ; Obesity/complications ; Prognosis ; Prospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {UNLABELLED: Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored.

METHOD: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors.

RESULTS: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April 2020, 23.7% died and 288 patients were at home at D30 post-discharge. At this date, 136 of them (47.2%) presented persistent malnutrition, a significant decrease in muscle strength or a PS ≥ 2. These patients received dietary counseling, nutritional supplementation, adapted physical activity guidance or physiotherapy assistance, or were admitted to post-care facilities. At 6 months post-discharge, 91.0% of the 136 patients (n = 119) were evaluated and 36.0% had persistent malnutrition, 14.3% complained of a significant decrease in muscle strength and 14.9% had a performance status > 2. Obesity was more frequent in patients with impairment than in those without (52.8% vs. 31.0%; p = 0.0071), with these patients being admitted more frequently to ICUs (50.9% vs. 31.3%; p = 0.010). Among those with persistent symptoms, 10% had psychiatric co-morbidities (mood disorders, anxiety, or post-traumatic stress syndrome), 7.6% had prolonged pneumological symptoms and 4.2% had neurological symptoms.

CONCLUSIONS: Obese subjects as well as patients who have stayed in intensive care have a higher risk of functional loss or undernutrition 6 months after a severe COVID infection. Malnutrition and loss of muscle strength should be considered in the clinical assessment of these patients.}, } @article {pmid34835130, year = {2021}, author = {Vollenberg, R and Tepasse, PR and Ochs, K and Floer, M and Strauss, M and Rennebaum, F and Kabar, I and Rovas, A and Nowacki, T}, title = {Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.}, journal = {Viruses}, volume = {13}, number = {11}, pages = {}, pmid = {34835130}, issn = {1999-4915}, mesh = {COVID-19/metabolism/*pathology ; Cross-Sectional Studies ; Endothelium, Vascular/pathology ; Female ; Glycocalyx/metabolism/*pathology ; Humans ; Inflammation ; Lung/pathology ; Male ; Middle Aged ; Prospective Studies ; Syndecan-1/*blood ; }, abstract = {The COVID-19 pandemic is caused by the SARS CoV-2 virus and can lead to severe lung damage and hyperinflammation. In the context of COVID-19 infection, inflammation-induced degradation of the glycocalyx layer in endothelial cells has been demonstrated. Syndecan-1 (SDC-1) is an established parameter for measuring glycocalyx injury. This prospective, multicenter, observational, cross-sectional study analyzed SDC-1 levels in 24 convalescent patients that had been infected with SARS-CoV-2 with mild disease course without need of hospitalization. We included 13 age-matched healthy individuals and 10 age-matched hospitalized COVID-19 patients with acute mild disease course as controls. In convalescent COVID-19 patients, significantly elevated SDC-1 levels were detected after a median of 88 days after symptom onset compared to healthy controls, whereas no difference was found when compared to SDC-1 levels of hospitalized patients undergoing acute disease. This study is the first to demonstrate signs of endothelial damage in non-pre-diseased, convalescent COVID-19 patients after mild disease progression without hospitalization. The data are consistent with studies showing evidence of persistent endothelial damage after severe or critical disease progression. Further work to investigate endothelial damage in convalescent COVID-19 patients should follow.}, } @article {pmid34834958, year = {2021}, author = {Messin, L and Puyraveau, M and Benabdallah, Y and Lepiller, Q and Gendrin, V and Zayet, S and Klopfenstein, T and Toko, L and Pierron, A and Royer, PY}, title = {COVEVOL: Natural Evolution at 6 Months of COVID-19.}, journal = {Viruses}, volume = {13}, number = {11}, pages = {}, pmid = {34834958}, issn = {1999-4915}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Body Mass Index ; COVID-19/*complications/epidemiology/*physiopathology ; Chronic Disease ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many studies have investigated post-COVID symptoms, but the predictors of symptom persistence remain unknown. The objective was to describe the natural course of the disease at 6 months and to identify possible factors favoring the resurgence or persistence of these symptoms. COVEVOL is a retrospective observational descriptive study of 74 patients. All patients with positive SARS-CoV-2 PCR from March 2020 were included. We compared a group with symptom persistence (PS group) with another group without symptom persistence (no-PS group). Fifty-three out of seventy-four patients (71.62%) described at least one persistent symptom at 6 months of SARS-CoV-2 infection. In the PS group, 56.6% were women and the average age was 54.7 years old [21-89.2] ± 16.9. The main symptoms were asthenia (56.6%, n = 30), dyspnea (34%, n = 18), anxiety (32.1% n = 17), anosmia (24.5%, n = 13) and agueusia (15.1% n = 8). Ten patients (13.51%) presented a resurgence in symptoms. Patients in the PS group were older (p = 0.0048), had a higher BMI (p = 0.0071), and were more frequently hospitalized (p = 0.0359) compared to the no-PS group. Odynophagia and nasal obstruction were less present in the inaugural symptoms of COVID-19 in the PS group (p = 0.0202 and p = 0.0332). Persistent post-COVID syndromes are common and identification of contributing factors is necessary for understanding this phenomenon and appropriate management.}, } @article {pmid34830872, year = {2021}, author = {De Winter, FHR and Hotterbeekx, A and Huizing, MT and Konnova, A and Fransen, E and Jongers, B and Jairam, RK and Van Averbeke, V and Moons, P and Roelant, E and Le Blon, D and Vanden Berghe, W and Janssens, A and Lybaert, W and Croes, L and Vulsteke, C and Malhotra-Kumar, S and Goossens, H and Berneman, Z and Peeters, M and van Dam, PA and Kumar-Singh, S}, title = {Blood Cytokine Analysis Suggests That SARS-CoV-2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients.}, journal = {Cancers}, volume = {13}, number = {22}, pages = {}, pmid = {34830872}, issn = {2072-6694}, support = {000100470//Kom Op Tegen Kanker/ ; 2020//UZA Foundation grant/ ; 42839//University of Antwerp/ ; s30729//University of Antwerp/ ; 115523 and 115737//Innovative Medicines Initiative/ ; Orchestra//Horizon 2020/ ; FWO-SB151525 and FWO-1S93418N//Research Foundation - Flanders/ ; }, abstract = {Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-β, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.}, } @article {pmid34830716, year = {2021}, author = {Jimeno-Almazán, A and Pallarés, JG and Buendía-Romero, Á and Martínez-Cava, A and Courel-Ibáñez, J}, title = {Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome.}, journal = {Journal of clinical medicine}, volume = {10}, number = {22}, pages = {}, pmid = {34830716}, issn = {2077-0383}, support = {2021//Cardiosalus/ ; 2020//Centro Médico Virgen de la Caridad/ ; }, abstract = {Patients recovering from COVID-19 commonly report persistence of dyspnea, exertional fatigue, and difficulties in carrying out their daily activities. However, the nature of these symptoms is still unknown. The purpose of the study was to identify limiting causes of cardiopulmonary origin for the performance of physical exercise in post-COVID-19 condition that could explain the symptomatic persistence of dyspnea or fatigue-related symptoms. Thirty-two non-hospitalized patients with post-COVID-19 condition (i.e., still presenting a chronic symptomatic phase lasting >90 days since debut of symptoms that lasted for at least 2 months and cannot be explained by an alternative diagnosis) completed a clinical examination including echocardiography, submaximal and maximal cardiorespiratory fitness tests (Ekblom-Bak and Bruce's protocols), and a battery of validated questionnaires about fatigue and exercise intolerance. Four participants (12.5%) reported an abnormal cardiac response to exercise during the submaximal test, which aroused suspicion of the presence of chronotropic incompetence. All of them were confirmed with a positive diagnosis maximal exercise test after cardiology screening, even with a comprehensive clinical examination, resting ECG, and echocardiogram, without other findings. No statistical differences were found in any physiological variables or questionnaire values, between patients with positive and negative diagnoses. Chronotropic incompetence and other autonomic disorders may appear in patients with mild forms of COVID-19 presentation and may persist in the long term, being responsible for exercise intolerance after resolution of acute infection. Clinicians should be aware that chronotropic incompetence and other autonomic disorders may be a complication of COVID-19 and should consider appropriate diagnostic and therapeutic interventions in these patients, especially when early exercise-related fatigability is reported.}, } @article {pmid34830550, year = {2021}, author = {Schambeck, SE and Crowell, CS and Wagner, KI and D'Ippolito, E and Burrell, T and Mijočević, H and Protzer, U and Busch, DH and Gerhard, M and Poppert, H and Beyer, H}, title = {Phantosmia, Parosmia, and Dysgeusia Are Prolonged and Late-Onset Symptoms of COVID-19.}, journal = {Journal of clinical medicine}, volume = {10}, number = {22}, pages = {}, pmid = {34830550}, issn = {2077-0383}, abstract = {Deficiencies in smell and taste are common symptoms of COVID-19. Quantitative losses are well surveyed. This study focuses on qualitative changes such as phantosmia (hallucination of smell), parosmia (alteration of smell), and dysgeusia (alteration of taste) and possible connections with the adaptive immune system. Subjective experience of deficiency in taste and smell was assessed by two different questionnaires after a median of 100 and 244 days after first positive RT-PCR test. SARS-CoV-2-specific antibody levels were measured with the iFlash-SARS-CoV-2 assay. After 100 days a psychophysical screening test for olfactory and gustatory dysfunction was administered. 30 of 44 (68.2%) participants reported a chemosensory dysfunction (14 quantitative, 6 qualitative, 10 quantitative, and qualitative) during COVID-19, eleven (25.0%) participants (1 quantitative, 7 qualitative, 3 quantitative, and quantity) after 100 days, and 14 (31.8%) participants (1 quantitative, 10 qualitative, 3 quantitative and qualitative) after 244 days. Four (9.1%) participants, who were symptom-free after 100 days reported now recently arisen qualitative changes. Serological and T-cell analysis showed no correlation with impairment of taste and smell. In conclusion, qualitative changes can persist for several months and occur as late-onset symptoms months after full recovery from COVID-19-induced quantitative losses in taste and smell.}, } @article {pmid34830303, year = {2021}, author = {Loke, XY and Imran, SAM and Tye, GJ and Wan Kamarul Zaman, WS and Nordin, F}, title = {Immunomodulation and Regenerative Capacity of MSCs for Long-COVID.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830303}, issn = {1422-0067}, support = {FF-2021-378//National University of Malaysia/ ; FPR-1//National University of Malaysia/ ; }, mesh = {COVID-19/*complications/pathology/therapy/virology ; Humans ; Immunomodulation/*physiology ; Lung/pathology/physiology ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology/metabolism ; Regeneration/*physiology ; Respiratory Distress Syndrome/pathology/therapy ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.}, } @article {pmid34829769, year = {2021}, author = {Utrero-Rico, A and Ruiz-Ruigómez, M and Laguna-Goya, R and Arrieta-Ortubay, E and Chivite-Lacaba, M and González-Cuadrado, C and Lalueza, A and Almendro-Vazquez, P and Serrano, A and Aguado, JM and Lumbreras, C and Paz-Artal, E}, title = {A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID.}, journal = {Biomedicines}, volume = {9}, number = {11}, pages = {}, pmid = {34829769}, issn = {2227-9059}, support = {COVID-19 research call COV20/00181//Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181) - co-financed by the European Development Regional Fund "A way to achieve Europe"/ ; CIVICO study 2020/0082//Consejeria de Sanidad de la Comunidad de Madrid/ ; }, abstract = {Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID.}, } @article {pmid34829406, year = {2021}, author = {Pelà, G and Goldoni, M and Cavalli, C and Perrino, F and Tagliaferri, S and Frizzelli, A and Mori, PA and Majori, M and Aiello, M and Sverzellati, N and Corradi, M and Chetta, A}, title = {Long-Term Cardiac Sequelae in Patients Referred into a Diagnostic Post-COVID-19 Pathway: The Different Impacts on the Right and Left Ventricles.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {34829406}, issn = {2075-4418}, abstract = {Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features' data about the acute phase along with information about the follow-up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-up of 5 months, echocardiography showed morpho-functional characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and bi-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High-Resolution computed tomography score and hemodynamic Instability (HI), and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies.}, } @article {pmid34828592, year = {2021}, author = {Brownlie, H and Speight, N}, title = {Back to the Future? Immunoglobulin Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {Healthcare (Basel, Switzerland)}, volume = {9}, number = {11}, pages = {}, pmid = {34828592}, issn = {2227-9032}, abstract = {The findings of controlled trials on use of intravenous immunoglobulin G (IV IgG) to treat myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are generally viewed as representing mixed results. On detailed review, a clearer picture emerges, which suggests that the potential therapeutic value of this intervention has been underestimated. Our analysis is consistent with the propositions that: (1) IgG is highly effective for a proportion of patients with severe and well-characterised ME/CFS; (2) responders can be predicted with a high degree of accuracy based on markers of immune dysfunction. Rigorous steps were taken in the research trials to record adverse events, with transient symptom exacerbation commonly experienced in both intervention and placebo control groups, suggesting that this reflected the impact of participation on people with an illness characterised by post-exertional symptom exacerbation. Worsening of certain specific symptoms, notably headache, did occur more commonly with IgG and may have been concomitant to effective treatment, being associated with clinical improvement. The findings emerging from this review are supported by clinical observations relating to treatment of patients with severe and very severe ME/CFS, for whom intramuscular and subcutaneous administration provide alternative options. We conclude that: (1) there is a strong case for this area of research to be revived; (2) pending further research, clinicians would be justified in offering a course of IgG to selected ME/CFS patients at the more severe end of the spectrum. As the majority of trial participants had experienced an acute viral or viral-like onset, we further suggest that IgG treatment may be pertinent to the care of some patients who remain ill following infection with SARS-CoV-2 virus.}, } @article {pmid34826844, year = {2021}, author = {Jarosch, I and Leitl, D and Koczulla, AR}, title = {[The pulmonary view on post-/Long-COVID].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {23}, pages = {1559-1563}, doi = {10.1055/a-1578-0347}, pmid = {34826844}, issn = {1439-4413}, mesh = {COVID-19/*complications/diagnosis/physiopathology/therapy ; Humans ; Lung/physiopathology ; Practice Guidelines as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {A majority of COVID patients suffers from hetereogenous symptoms after acute infection which are limiting patients participation in social life, activities of daily living and the return to work. In March 2021, the German Society of Pneumology initiated the AWMF S1 guideline Post-COVID/Long-COVID in order to show an individual practice-oriented, diagnostic and therapeutic clinical algorithm according to the individual symptoms. This article is based on the S1 guideline and highlights some trials of interest with a focus on pulmonary symptoms. The guideline and, accordingly, this article have an explicitly practical and clinical purpose. The guideline will be further developed by the author team based on the current increase in knowledge this is reflected in the clinical summary article.}, } @article {pmid34826619, year = {2022}, author = {Lledó, GM and Sellares, J and Brotons, C and Sans, M and Antón, JD and Blanco, J and Bassat, Q and Sarukhan, A and Miró, JM and de Sanjosé, S and , }, title = {Post-acute COVID-19 syndrome: a new tsunami requiring a universal case definition.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {3}, pages = {315-318}, pmid = {34826619}, issn = {1469-0691}, mesh = {*COVID-19/complications/diagnosis ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34824074, year = {2021}, author = {Thompson, DR and Al-Jabr, H and Windle, K and Ski, CF}, title = {Long COVID: supporting people through the quagmire.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {713}, pages = {561}, pmid = {34824074}, issn = {1478-5242}, mesh = {*COVID-19/complications/epidemiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34824040, year = {2022}, author = {Vallejo Camazón, N and Teis, A and Martínez Membrive, MJ and Llibre, C and Bayés-Genís, A and Mateu, L}, title = {Long COVID-19 and microvascular disease-related angina.}, journal = {Revista espanola de cardiologia (English ed.)}, volume = {75}, number = {5}, pages = {444-446}, pmid = {34824040}, issn = {1885-5857}, mesh = {*COVID-19/complications ; Coronary Circulation ; Humans ; Microcirculation ; *Microvascular Angina/diagnosis/etiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34821709, year = {2021}, author = {Bisaccia, G and Ricci, F and Recce, V and Serio, A and Iannetti, G and Chahal, AA and Ståhlberg, M and Khanji, MY and Fedorowski, A and Gallina, S}, title = {Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?.}, journal = {Journal of cardiovascular development and disease}, volume = {8}, number = {11}, pages = {}, pmid = {34821709}, issn = {2308-3425}, abstract = {Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and "brain fog". Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.}, } @article {pmid34820848, year = {2022}, author = {Wechsler, JB and Butuci, M and Wong, A and Kamboj, AP and Youngblood, BA}, title = {Mast cell activation is associated with post-acute COVID-19 syndrome.}, journal = {Allergy}, volume = {77}, number = {4}, pages = {1288-1291}, pmid = {34820848}, issn = {1398-9995}, support = {//Allakos, Inc/ ; }, mesh = {*COVID-19/complications ; Cytokines ; Humans ; Immunity, Innate ; Inflammation ; Mast Cells ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34820152, year = {2021}, author = {Roth, A and Chan, PS and Jonas, W}, title = {Addressing the Long COVID Crisis: Integrative Health and Long COVID.}, journal = {Global advances in health and medicine}, volume = {10}, number = {}, pages = {21649561211056597}, pmid = {34820152}, issn = {2164-957X}, abstract = {While COVID-19 has killed millions of people globally, its lasting effects on the health and well-being of entire populations are just becoming clear. As many as 30% of those diagnosed with COVID-19 report continuing health-related problems, regardless of the severity of the initial infection. Given the infection rate in the world, that translates to between 5.4 and 17.9 million globally; about 700 000 in the US. The syndrome goes by many names; here we call it "long COVID." Patients experience a wide range of symptoms, including serious organ system effects such as pulmonary fibrosis, myocarditis, new diabetes diagnoses, stroke, and other cerebrovascular events. They also experience ongoing pain, fatigue, and cognitive dysfunction. We suggest here that these patients require an integrative health approach, one that combines traditional medical management, non-pharmacological approaches, and behavior and lifestyle changes. Such an approach has been shown to be beneficial in other chronic illnesses such as fibromyalgia, chronic fatigue syndrome, and post-Lyme disease.}, } @article {pmid34820130, year = {2021}, author = {Rheault, S}, title = {Severe COVID-19 and long COVID in a 31-year-old woman with incontinentia pigmenti: A case report.}, journal = {SAGE open medical case reports}, volume = {9}, number = {}, pages = {2050313X211059295}, pmid = {34820130}, issn = {2050-313X}, abstract = {Incontinentia pigmenti is a rare genetic disease affecting the skin, microvasculature, and central nervous system, in which a hyperactive inflammatory response is observed. Due to the inflammatory phase of COVID-19 and associated cytokine storm, infection with SARS-CoV-2 in individuals with incontinentia pigmenti is a concern. Furthermore, type I interferon autoantibodies are found in life-threatening COVID-19 pneumonia and in 25% of individuals with incontinentia pigmenti. The present case report describes a 31-year-old Caucasian woman with incontinentia pigmenti and severe COVID-19. She was hospitalized for oxygen therapy, intravenous antibiotics, and corticosteroids. Eight months later, she is still symptomatic. To our knowledge, she is the first reported case of long COVID in incontinentia pigmenti. Increased autoimmunity may be implicated in both incontinentia pigmenti and long COVID. Pending evidence-based guidelines, COVID-protective measures including vaccination should be recommended to all patients with incontinentia pigmenti. Specific interferon therapy may be considered along with usual COVID treatment.}, } @article {pmid34817268, year = {2022}, author = {Desai, AD and Lavelle, M and Boursiquot, BC and Wan, EY}, title = {Long-term complications of COVID-19.}, journal = {American journal of physiology. Cell physiology}, volume = {322}, number = {1}, pages = {C1-C11}, pmid = {34817268}, issn = {1522-1563}, support = {R01 HL152236/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; COVID-19/*complications/etiology/*physiopathology ; Cardiovascular Diseases/etiology ; Central Nervous System Diseases/etiology ; Disease Progression ; Hematologic Diseases/etiology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our understanding of both short-term and long-term complications of infection with SARS-CoV-2 continues to grow as well. Just as there is heterogeneity in the acute infectious phase, there is heterogeneity in the long-term complications seen following COVID-19 illness. The purpose of this review article is to present the current literature with regards to the epidemiology, pathophysiology, and proposed management algorithms for the various long-term sequelae that have been observed in each organ system following infection with SARS-CoV-2. We will also consider future directions, with regards to newer variants of the virus and their potential impact on the long-term complications observed.}, } @article {pmid34816207, year = {2021}, author = {Newson, L and Manyonda, I and Lewis, R and Preissner, R and Preissner, S and Seeland, U}, title = {Sensitive to Infection but Strong in Defense-Female Sex and the Power of Oestradiol in the COVID-19 Pandemic.}, journal = {Frontiers in global women's health}, volume = {2}, number = {}, pages = {651752}, pmid = {34816207}, issn = {2673-5059}, abstract = {The incidence of SARS-CoV2 infections is around 15% higher in premenopausal women compared to age matched men, yet the fatality rate from COVID-19 is significantly higher in men than women for all age strata. Sex differences have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), with SARS-CoV 2 virus infection sex differences appear more dramatic. The regulation and expression of the angiotensin converting enzyme 2 (ACE2) is the key for this special coronavirus SARS-CoV-2 to enter the cell. 17β-oestradiol increases expression level and activity of angiotensin converting enzyme-2 (ACE2) and the alternative signaling pathway of Ang II via the angiotensin II receptor type II (AT2R) and the Mas receptor is more dominant in female sex than in male sex. Maybe a hint to explain the higher infection risk in women. The same hormonal milieu plays a major role in protecting women where morbidity and mortality are concerned, since the dominant female hormone, oestradiol, has immune-modulatory properties that are likely to be protective against virus infections. It is also known that the X chromosome contains the largest number of immune-related genes, potentially conferring an advantage to women in efficient immune responsiveness. Lifestyle factors are also likely to be contributory. Premenopausal women could possibly face higher exposure to infection (hence higher infection rates) because economic conditions are often less favorable for them with less opportunity for home office work because of jobs requiring mandatory attendance. Due to the additional task of childcare, it is likely that contact times with other people will be longer. Women generally make healthier lifestyle choices, thus reducing the disease burden that confers high risk of mortality in COVID-19 infected men. This narrative review aims to present key concepts and knowledge gaps on the effects of oestrogen associated with SARS-CoV2 infection and COVID-19 disease.}, } @article {pmid34815580, year = {2021}, author = {Ledford, H}, title = {Do vaccines protect against long COVID? What the data say.}, journal = {Nature}, volume = {599}, number = {7886}, pages = {546-548}, pmid = {34815580}, issn = {1476-4687}, mesh = {Acute Disease/epidemiology ; COVID-19/*complications/epidemiology/physiopathology/prevention & control/rehabilitation ; COVID-19 Vaccines/administration & dosage/*immunology ; Chronic Disease/epidemiology/prevention & control ; Humans ; Immunization, Secondary ; Neurological Rehabilitation ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34813820, year = {2022}, author = {Behnood, SA and Shafran, R and Bennett, SD and Zhang, AXD and O'Mahoney, LL and Stephenson, TJ and Ladhani, SN and De Stavola, BL and Viner, RM and Swann, OV}, title = {Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies.}, journal = {The Journal of infection}, volume = {84}, number = {2}, pages = {158-170}, pmid = {34813820}, issn = {1532-2742}, mesh = {Adolescent ; *COVID-19 ; Child ; Fatigue ; Fever/etiology ; Headache/complications/etiology ; Humans ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration.

METHODS: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153.

FINDINGS: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99-231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms.

INTERPRETATION: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.}, } @article {pmid34813382, year = {2022}, author = {Vaira, LA and Salzano, G and Le Bon, SD and Maglio, A and Petrocelli, M and Steffens, Y and Ligas, E and Maglitto, F and Lechien, JR and Saussez, S and Vatrella, A and Salzano, FA and Boscolo-Rizzo, P and Hopkins, C and De Riu, G}, title = {Prevalence of Persistent Olfactory Disorders in Patients With COVID-19: A Psychophysical Case-Control Study With 1-Year Follow-up.}, journal = {Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery}, volume = {167}, number = {1}, pages = {183-186}, doi = {10.1177/01945998211061511}, pmid = {34813382}, issn = {1097-6817}, mesh = {Anosmia ; *COVID-19/epidemiology ; Case-Control Studies ; Follow-Up Studies ; Humans ; *Olfaction Disorders/epidemiology ; Prevalence ; Smell ; }, abstract = {The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.}, } @article {pmid34811716, year = {2022}, author = {Szarpak, L and Pruc, M and Filipiak, KJ and Popieluch, J and Bielski, A and Jaguszewski, MJ and Gilis-Malinowska, N and Chirico, F and Rafique, Z and Peacock, FW}, title = {Myocarditis: A complication of COVID-19 and long-COVID-19 syndrome as a serious threat in modern cardiology.}, journal = {Cardiology journal}, volume = {29}, number = {1}, pages = {178-179}, pmid = {34811716}, issn = {1898-018X}, mesh = {*COVID-19/complications ; *Cardiology ; Humans ; *Myocarditis/diagnosis/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34811549, year = {2022}, author = {Routen, A and O'Mahoney, L and Ayoubkhani, D and Banerjee, A and Brightling, C and Calvert, M and Chaturvedi, N and Diamond, I and Eggo, R and Elliott, P and Evans, RA and Haroon, S and Herret, E and O'Hara, ME and Shafran, R and Stanborough, J and Stephenson, T and Sterne, J and Ward, H and Khunti, K}, title = {Understanding and tracking the impact of long COVID in the United Kingdom.}, journal = {Nature medicine}, volume = {28}, number = {1}, pages = {11-15}, pmid = {34811549}, issn = {1546-170X}, support = {MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_20049/MRC_/Medical Research Council/United Kingdom ; MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_19012/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications/epidemiology/pathology/virology ; Humans ; Pandemics ; SARS-CoV-2/isolation & purification ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34810378, year = {2021}, author = {Balaji, SM}, title = {Long COVID-19 and dental treatment.}, journal = {Indian journal of dental research : official publication of Indian Society for Dental Research}, volume = {32}, number = {2}, pages = {139}, doi = {10.4103/ijdr.IJDR_959_21}, pmid = {34810378}, issn = {1998-3603}, mesh = {*COVID-19/complications ; Dental Care ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34808607, year = {2021}, author = {Wood, J and Tabacof, L and Tosto-Mancuso, J and McCarthy, D and Kontorovich, A and Putrino, D}, title = {Levels of end-tidal carbon dioxide are low despite normal respiratory rate in individuals with long COVID.}, journal = {Journal of breath research}, volume = {16}, number = {1}, pages = {}, doi = {10.1088/1752-7163/ac3c18}, pmid = {34808607}, issn = {1752-7163}, mesh = {Breath Tests ; *COVID-19/complications ; Capnography ; *Carbon Dioxide ; Humans ; Respiratory Rate ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34803561, year = {2021}, author = {Facharztmagazine, R}, title = {[Not Available].}, journal = {CME (Berlin, Germany)}, volume = {18}, number = {11}, pages = {6}, doi = {10.1007/s11298-021-2240-7}, pmid = {34803561}, issn = {1614-3744}, } @article {pmid34803536, year = {2021}, author = {Lovie, H}, title = {Gu Syndrome, Lurking Pathogens, and Long Covid: An Old Take on a New Disease.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {20}, number = {5}, pages = {22-24}, pmid = {34803536}, issn = {1546-993X}, } @article {pmid34803180, year = {2022}, author = {López-Sampalo, A and Bernal-López, MR and Gómez-Huelgas, R}, title = {[Persistent COVID-19 syndrome. A narrative review].}, journal = {Revista clinica espanola}, volume = {222}, number = {4}, pages = {241-250}, pmid = {34803180}, issn = {1578-1860}, abstract = {As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.}, } @article {pmid34802495, year = {2021}, author = {Mohamed-Hussein, AAR and Amin, MT and Makhlouf, HA and Makhlouf, NA and Galal, I and Abd-Elaal, HK and Abdeltawab, D and Kholief, KMS and Hashem, MK}, title = {Non-hospitalised COVID-19 patients have more frequent long COVID-19 symptoms.}, journal = {The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease}, volume = {25}, number = {9}, pages = {732-737}, doi = {10.5588/ijtld.21.0135}, pmid = {34802495}, issn = {1815-7920}, mesh = {*COVID-19/complications/epidemiology ; Cross-Sectional Studies ; Hospitalization ; Humans ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID-19 syndrome refers to the persistence of symptoms for more than 12 weeks after the start of acute symptoms. The pathophysiology of this syndrome is not yet clear.OBJECTIVE: To assess long COVID-19 symptoms in hospitalised and non-hospitalised patients.METHODS: A cross-sectional survey was used. The study included 262 patients who were divided into two groups based on their hospital admission history: 167 (63.7%) were not hospitalised, while 95 (36.3%) were hospitalised.RESULTS: Long-COVID was reported in 157 out of 262 patients (59.9%), and was significantly more frequent in non-hospitalised patients (68.3% vs. 45.3%; P < 0.001). During the acute phase, hospitalised patients had more respiratory symptoms (95.9% vs. 85.6%), while non-hospitalised patients had more neuropsychiatric symptoms (84.4% vs. 69.5%; P < 0.05). Constitutional and neuropsychiatric symptoms were the most frequently reported persistent symptoms in both groups, but all persistent symptoms were more frequent in the non-hospitalised group (P < 0.005).CONCLUSION: Long COVID-19 symptoms affect both hospitalised and non-hospitalised patients. Neuropsychiatric manifestations were the most common persistent COVID-19 symptoms. Rehabilitation and psychotherapy could be advised for all recovered COVID-19 patients. Non-hospitalised COVID-19 patients should be counselled to contact healthcare providers whenever needed.}, } @article {pmid34794857, year = {2022}, author = {Chan, G and Narang, A and Aframian, A and Ali, Z and Bridgeman, J and Carr, A and Chapman, L and Goodier, H and Morgan, C and Park, C and Sexton, S and Sugand, K and Walton, T and Wilson, M and Belgaumkar, A and Gallagher, K and Ghosh, K and Gibbons, C and Jacob, J and Keightley, A and Nawaz, Z and Sarraf, K and Wakeling, C and Kieffer, W and Rogers, B}, title = {Medium-term mortality after hip fractures and COVID-19: A prospective multi-centre UK study.}, journal = {Chinese journal of traumatology = Zhonghua chuang shang za zhi}, volume = {25}, number = {3}, pages = {161-165}, pmid = {34794857}, issn = {1008-1275}, mesh = {*COVID-19 ; *Hip Fractures/surgery ; Humans ; Pandemics ; Prospective Studies ; Retrospective Studies ; State Medicine ; United Kingdom/epidemiology ; }, abstract = {PURPOSE: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture.

METHODS: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27.

RESULTS: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978).

CONCLUSION: Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture.}, } @article {pmid34793374, year = {2021}, author = {Morrow, AK and Ng, R and Vargas, G and Jashar, DT and Henning, E and Stinson, N and Malone, LA}, title = {Postacute/Long COVID in Pediatrics: Development of a Multidisciplinary Rehabilitation Clinic and Preliminary Case Series.}, journal = {American journal of physical medicine & rehabilitation}, volume = {100}, number = {12}, pages = {1140-1147}, pmid = {34793374}, issn = {1537-7385}, mesh = {Adolescent ; Anxiety/rehabilitation/virology ; COVID-19/*complications/diagnosis/psychology/*rehabilitation ; Child ; Fatigue/rehabilitation/virology ; Female ; Headache/rehabilitation/virology ; Humans ; Male ; Neuropsychological Tests ; *Patient Care Team ; Pediatrics/*methods ; Quality of Life ; SARS-CoV-2 ; Subacute Care/*methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {The long-term sequelae after SARS-CoV-2 infections in children is unknown. Guidance is needed on helpful models of care for an emerging subset of pediatric patients with postacute/long COVID who continue to experience persistent symptoms after initial COVID-19 diagnosis. Here, we describe a pediatric multidisciplinary post-COVID-19 rehabilitation clinic model as well as a case series of the initial cohort of patients who presented to this clinic. A consecutive sample of nine patients (pediatric patients <21 yrs of age) who presented to our clinic are included. The most common presenting symptoms were fatigue (8 of 9 patients), headaches (6 of 9), difficulty with schoolwork (6 of 8), "brain fog" (4 of 9), and dizziness/lightheadedness (4 of 9). Most patients had decreased scores on self-reported quality-of-life measures compared with healthy controls. In the patients who participated in neuropsychological testing, a subset demonstrated difficulties with sustained auditory attention and divided attention; however, most of these patients had preexisting attention and/or mood concerns. There were also some who self-reported elevated depression and anxiety symptoms. Pediatric patients with postacute/long COVID may present with a variety of physical, cognitive, and mood symptoms. We present a model of care to address these symptoms through a multidisciplinary rehabilitation approach.}, } @article {pmid34793373, year = {2021}, author = {Verduzco-Gutierrez, M and Estores, IM and Graf, MJP and Barshikar, S and Cabrera, JA and Chang, LE and Eapen, BC and Bell, KR}, title = {Models of Care for Postacute COVID-19 Clinics: Experiences and a Practical Framework for Outpatient Physiatry Settings.}, journal = {American journal of physical medicine & rehabilitation}, volume = {100}, number = {12}, pages = {1133-1139}, pmid = {34793373}, issn = {1537-7385}, mesh = {Ambulatory Care/*methods ; COVID-19/*complications/*rehabilitation ; Humans ; Physical and Rehabilitation Medicine/*methods ; SARS-CoV-2 ; Subacute Care/*methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {After surviving infection with the SARS-CoV-2 virus, individuals may have persistent symptoms and prolonged impairments that may last for weeks to months. The frequency and heterogeneity of persistent post-COVID conditions have created challenges in care. Specialty clinics are being established in response to an increasing need to care for patients with postacute sequelae of SARS-CoV-2 or long COVID syndrome. Although many post-COVID conditions can be bettered through a comprehensive rehabilitation plan, various clinical settings may benefit from differing models of coordinated care. We present five models of care in varying degrees of development and compare processes and adaptations to address the unique needs of each center and their unique patient populations. Forging a path to recovery will necessitate a multidisciplinary team with physiatry involvement to meet the distinctive needs of patients with postacute sequelae of SARS-CoV-2. Furthermore, it is imperative that there be equitable access to this care and commitment from healthcare institutions to provide resources for these programs.}, } @article {pmid34790680, year = {2021}, author = {Hayes, LD and Ingram, J and Sculthorpe, NF}, title = {More Than 100 Persistent Symptoms of SARS-CoV-2 (Long COVID): A Scoping Review.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {750378}, pmid = {34790680}, issn = {2296-858X}, support = {COV/LTE/20/08/CSO_/Chief Scientist Office/United Kingdom ; }, abstract = {Background: Persistent coronavirus disease 2019 (COVID-19) symptoms are increasingly well-reported in cohort studies and case series. Given the spread of the pandemic, number of individuals suffering from persistent symptoms, termed 'long COVID', are significant. However, type and prevalence of symptoms are not well reported using systematic literature reviews. Objectives: In this scoping review of the literature, we aggregated type and prevalence of symptoms in people with long COVID. Eligibility Criteria: Original investigations concerning the name and prevalence of symptoms were considered in participants ≥4-weeks post-infection. Sources of Evidence: Four electronic databases [Medline, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL)] were searched. Methods: A scoping review was conducted using the Arksey and O'Malley framework. Review selection and characterisation was performed by three independent reviewers using pretested forms. Results: Authors reviewed 2,711 titles and abstracts for inclusion with 152 selected for full-text review. 102 articles were subsequently removed as this did not meet inclusion criteria. Thus, fifty studies were analysed, 34 of which were described as cohort studies or prospective cohort studies, 14 were described as cross-sectional studies, one was described as a case control study, and one was described as a retrospective observational study. In total, >100 symptoms were identified and there was considerable heterogeneity in symptom prevalence and setting of study. Ten studies reported cardiovascular symptoms, four examined pulmonary symptoms, 25 reported respiratory symptoms, 24 reported pain-related symptoms, 21 reported fatigue, 16 reported general infection symptoms, 10 reported symptoms of psychological disorders, nine reported cognitive impairment, 31 reported a sensory impairment, seven reported a dermatological complaint, 11 reported a functional impairment, and 18 reported a symptom which did not fit into any of the above categories. Conclusion: Most studies report symptoms analogous to those apparent in acute COVID-19 infection (i.e., sensory impairment and respiratory symptoms). Yet, our data suggest a larger spectrum of symptoms, evidenced by >100 reported symptoms. Symptom prevalence varied significantly and was not explained by data collection approaches, study design or other methodological approaches, and may be related to unknown cohort-specific factors.}, } @article {pmid34787782, year = {2022}, author = {Lamb, LE and Timar, R and Wills, M and Dhar, S and Lucas, SM and Komnenov, D and Chancellor, MB and Dhar, N}, title = {Long COVID and COVID-19-associated cystitis (CAC).}, journal = {International urology and nephrology}, volume = {54}, number = {1}, pages = {17-21}, pmid = {34787782}, issn = {1573-2584}, mesh = {Aged ; Aged, 80 and over ; COVID-19/*complications/epidemiology/etiology ; Cystitis/epidemiology/*etiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Pandemics ; *Quality of Life ; *SARS-CoV-2 ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: There is scarce literature regarding genitourinary symptoms in COVID-19, especially post-acute disease otherwise known as Long COVID. We identified recovered COVID-19 patients presenting with new or worsening overactive bladder symptoms, known as COVID-19-associated cystitis (CAC).

METHODS: We used the American Urological Association Urology Care Foundation Overactive Bladder (OAB) Assessment Tool to screen COVID-19 recovered patients presenting with urological complaints at our urban-located institution from 5/22/2020 to 12/31/2020. Patients 10-14 weeks post-discharge responded to 5 symptom and 4 quality-of-life (QoL) questions. We reported median symptom scores, as well as QoL scores, based on new or worsening urinary symptoms, and by sex.

RESULTS: We identified 350 patients with de novo or worsening OAB symptoms 10-14 weeks after hospitalization with COVID-19. The median total OAB symptom score in both men and women was 18. The median total QoL score for both men and women was 19. Patients with worsening OAB symptoms had a median pre-COVID-19 symptom score of 8 (4-10) compared to post-COVID-19 median symptom score of 19 (17-21). Median age was 64.5 (range 47-82). Median hospital length-of-stay was 10 days (range 5-30).

CONCLUSION: We report survey-based results of patients suffering from new or worsening OAB symptoms months after their hospitalization from COVID-19. Future studies with larger sample sizes and more extensive testing will hopefully elucidate the specific pathophysiology of OAB symptoms in the context of long COVID so urologists can timely and appropriately treat their patients.}, } @article {pmid34783052, year = {2022}, author = {Sivan, M and Parkin, A and Makower, S and Greenwood, DC}, title = {Post-COVID syndrome symptoms, functional disability, and clinical severity phenotypes in hospitalized and nonhospitalized individuals: A cross-sectional evaluation from a community COVID rehabilitation service.}, journal = {Journal of medical virology}, volume = {94}, number = {4}, pages = {1419-1427}, pmid = {34783052}, issn = {1096-9071}, support = {MC_PC_19042/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; COVID-19/*rehabilitation ; Community Health Services/methods/*organization & administration ; Critical Pathways/*organization & administration ; Cross-Sectional Studies ; Disability Evaluation ; Female ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Phenotype ; *SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {There is currently limited information on clinical severity phenotypes of symptoms and functional disability in post-coronavirus disease 2019 (COVID) Syndrome (PCS). A purposive sample of 370 PCS patients from a dedicated community COVID-19 rehabilitation service was assessed using the COVID-19 Yorkshire Rehabilitation Scale where each symptom or functional difficulty was scored on a 0-10 Likert scale and also compared with before infection. Phenotypes based on symptom severity were extracted to identify any noticeable patterns. The correlation between symptom severity, functional disability, and overall health was explored. The mean age was 47 years, with 237 (64%) females. The median duration of symptoms was 211 days (interquartile range 143-353). Symptoms and functional difficulties increased substantially when compared to before infection. Three distinct severity phenotypes of mild (n = 90), moderate (n = 186), and severe (n = 94) were identified where the severity of individual symptoms was of similar severity within each phenotype. Symptom scores were strongly positively correlated with functional difficulty scores (0.7, 0.6-0.7) and moderately negatively correlated with overall health (-0.4, -0.3, to -0.5). This is the first study reporting on severity phenotypes in a largely nonhospitalized PCS cohort. Severity phenotypes might help stratify patients for targeted interventions and planning of care pathways.}, } @article {pmid34778143, year = {2021}, author = {Roge, I and Smane, L and Kivite-Urtane, A and Pucuka, Z and Racko, I and Klavina, L and Pavare, J}, title = {Comparison of Persistent Symptoms After COVID-19 and Other Non-SARS-CoV-2 Infections in Children.}, journal = {Frontiers in pediatrics}, volume = {9}, number = {}, pages = {752385}, pmid = {34778143}, issn = {2296-2360}, abstract = {Introduction: The data on long COVID in children is scarce since children and adolescents are typically less severely affected by acute COVID-19. This study aimed to identify the long-term consequences of SARS-CoV-2 infection in children, and to compare the persistent symptom spectrum between COVID-19 and community-acquired infections of other etiologies. Methods: This was an ambidirectional cohort study conducted at the Children's Clinical University Hospital in Latvia. The study population of pediatric COVID-19 patients and children with other non-SARS-CoV-2-community-acquired infections were invited to participate between July 1, 2020, and April 30, 2021. Results: In total, 236 pediatric COVID-19 patients were enrolled in the study. Additionally, 142 comparison group patients were also enrolled. Median follow-up time from acute symptom onset was 73.5 days (IQR; 43-110 days) in the COVID-19 patient group and 69 days (IQR, 58-84 days) in the comparison group. Most pediatric COVID-19 survivors (70%, N = 152) reported at least one persistent symptom, but more than half of the patients (53%, N = 117) noted two or more long-lasting symptoms. The most commonly reported complaints among COVID-19 patients included persistent fatigue (25.2%), cognitive sequelae, such as irritability (24.3%), and mood changes (23.3%), as well as headaches (16.9%), rhinorrhea (16.1%), coughing (14.4%), and anosmia/dysgeusia (12.3%). In addition, 105 (44.5%) COVID patients had persistent symptoms after the 12-week cut-off point, with irritability (27.6%, N = 29), mood changes (26.7%, N = 28), and fatigue (19.2%, N = 20) being the most commonly reported ones. Differences in symptom spectrum among the various age groups were seen. Logistic regression analysis showed that long-term persistent symptoms as fever, fatigue, rhinorrhea, loss of taste and/or smell, headaches, cognitive sequelae, and nocturnal sweating were significantly associated with the COVID-19 experience when compared with the controls. Conclusions: We found that at the time of interview almost three-quarters of children reported at least one persistent symptom, but the majority of patients (53%) had two or more concurrent symptoms. The comparison group's inclusion in the study allowed us to identify that symptom persistence is more apparent with COVID-19 than any other non-SARS-CoV-2 infection. More research is needed to distinguish the symptoms of long COVID from pandemic-associated complaints. Each persistent symptom is important in terms of child well-being during COVID-19 recovery.}, } @article {pmid34775534, year = {2022}, author = {Tiseo, G and Yahav, D and Paul, M and Tinelli, M and Gavazzi, G and Mussini, C and Prendki, V and Falcone, M}, title = {What have we learned from the first to the second wave of COVID-19 pandemic? An international survey from the ESCMID Study Group for Infection in the Elderly (ESGIE) group.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {41}, number = {2}, pages = {281-288}, pmid = {34775534}, issn = {1435-4373}, mesh = {*COVID-19/epidemiology ; Drug Combinations ; Humans ; Hydroxychloroquine/therapeutic use ; Intensive Care Units ; Lopinavir ; *Pandemics ; Ritonavir ; Surveys and Questionnaires ; *COVID-19 Drug Treatment ; }, abstract = {The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO2/FiO2 200-350) and severe (PiO2/FiO2 < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians.}, } @article {pmid34774190, year = {2021}, author = {Ward, H and Flower, B and Garcia, PJ and Ong, SWX and Altmann, DM and Delaney, B and Smith, N and Elliott, P and Cooke, G}, title = {Global surveillance, research, and collaboration needed to improve understanding and management of long COVID.}, journal = {Lancet (London, England)}, volume = {398}, number = {10316}, pages = {2057-2059}, pmid = {34774190}, issn = {1474-547X}, support = {MC_PC_19012/MRC_/Medical Research Council/United Kingdom ; MC_PC_20049/MRC_/Medical Research Council/United Kingdom ; MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications ; *Chronic Disease ; Cognitive Dysfunction/etiology ; *Disease Management ; Fatigue/etiology ; Humans ; *Population Surveillance ; Research ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34772779, year = {2021}, author = {Vance, H and Maslach, A and Stoneman, E and Harmes, K and Ransom, A and Seagly, K and Furst, W}, title = {Addressing Post-COVID Symptoms: A Guide for Primary Care Physicians.}, journal = {Journal of the American Board of Family Medicine : JABFM}, volume = {34}, number = {6}, pages = {1229-1242}, doi = {10.3122/jabfm.2021.06.210254}, pmid = {34772779}, issn = {1558-7118}, mesh = {*COVID-19 ; Humans ; *Physicians, Primary Care ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Post-COVID symptoms, defined as symptoms lasting >4 weeks postinfection, have been identified not only among those patients who were hospitalized with severe symptoms but also among those who were asymptomatic or with only mild symptoms. Primary care providers (PCPs) will often be the first point of contact for patients experiencing potential complications of post-COVID symptoms. The aim of this article is to present a post-COVID management tool for PCPs to use as a quick reference and guide to the initial workup and management of the most common post-COVID symptoms.

METHODS: Published guidance, recent literature, and expert specialist opinion were used to create the structure outlining the outpatient evaluation and treatment for post-COVID symptoms.

RESULTS: A quick-reference guide for management of post-COVID symptoms was created for PCPs. Educational materials were created for clinicians to share with patients. Our article reviews several common complaints including respiratory, cognitive, and neurological symptoms, chronic fatigue, dysautonomia, and anosmia and presents recommendations for management.

CONCLUSIONS: Data on long-term effects of COVID-19 are still emerging, and rapid dissemination of this data to front-line PCPs is crucial. This table was our effort to make the currently available evidence accessible for our PCPs in a simple, easy-to-use format.}, } @article {pmid34769973, year = {2021}, author = {Džubera, A and Chochol, J and Illéš, R and Chocholová, A and Zemková, E}, title = {Vertebral Algic Syndrome Treatment in Long COVID-Cases Reports.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {21}, pages = {}, pmid = {34769973}, issn = {1660-4601}, support = {INTERREG V-A SK-CZ/2018/06 (No. 304011P714)//the Cross-border Co-operation Programme INTERREG V-A SK-CZ/2018/06 (No. 304011P714)/ ; }, mesh = {*COVID-19/complications ; Decompression, Surgical ; Humans ; *Radiculopathy/surgery ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Though pain is a frequent symptom of long COVID-19, little attention has been paid to vertebral algic syndrome. Therefore, we present the cases reports of two precisely selected physically active patients where vertebral algic syndrome and radiculopathy dramatically worsened in acute SARS-CoV-2 infections. The vertebral pain with radicular irritation was resistant to conservative treatment in chronic post-COVID syndrome. The neurological difficulties corresponded to the radiologic imaging presented on MRI scans. Due to the absence of standard therapeutic guidelines in literature sources, it was decided to provide routine therapeutic procedures. Spinal surgery with radicular decompression was performed within 6 months after acute SARS-CoV-2 infection. This led to the improvement of their neurological status and was in corroboration with decreases of VAS (from 9 to 0 in Patient 1 and from 7 to 1 in Patient 2). Our experience indicates that these patients benefited from the standard neurosurgical radicular decompression, and sufficient pain relief was achieved; nevertheless, the initial trigger of neurological worsening was acute SARS-CoV-2 infection.}, } @article {pmid34769934, year = {2021}, author = {Shelley, J and Hudson, J and Mackintosh, KA and Saynor, ZL and Duckers, J and Lewis, KE and Davies, GA and Berg, RMG and McNarry, MA}, title = {'I Live a Kind of Shadow Life': Individual Experiences of COVID-19 Recovery and the Impact on Physical Activity Levels.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {21}, pages = {}, pmid = {34769934}, issn = {1660-4601}, support = {SER1032//Llywodraeth Cymru/ ; FF4 (RWIF Collaboration Booster Faculty Fund)//Higher Education Funding Council for Wales/ ; }, mesh = {*Activities of Daily Living ; Adult ; *COVID-19/complications ; Exercise ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. 'Long COVID' is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals' experiences of recovering from COVID-19 to provide a better understanding of the acute and long-term impact of the disease on physical activity (PA). Individualised semi-structured interviews were conducted with 48 adults recovering from COVID-19 at 6-11 months post-infection. An inductive thematic analysis approach was used, reaching saturation at 14 interviews (10 female; 47 ± 7 years). Four overarching themes were identified: (i) Living with COVID-19, including managing activities of daily living; (ii) Dealing with the Unknown and self-management strategies; (iii) Re-introducing physical activity; and (iv) Challenges of returning to work. The return to PA, whether through activities of daily living, work or exercise, is often associated with the exacerbation of symptoms, presenting a range of challenges for individuals recovering from COVID-19. Individually tailored support is therefore required to address the unique challenges posed by COVID-19.}, } @article {pmid34768725, year = {2021}, author = {Malinowska, A and Muchlado, M and Ślizień, Z and Biedunkiewicz, B and Heleniak, Z and Dębska-Ślizień, A and Tylicki, L}, title = {Post-COVID-19 Sydrome and Decrease in Health-Related Quality of Life in Kidney Transplant Recipients after SARS-COV-2 Infection-A Cohort Longitudinal Study from the North of Poland.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768725}, issn = {2077-0383}, abstract = {INTRODUCTION: Patients after SARS-CoV-2 infection frequently face "Post-COVID-19 Syndrome", defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease.

MATERIALS AND METHODS: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale.

RESULTS: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity.

CONCLUSIONS: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs.}, } @article {pmid34765889, year = {2021}, author = {, }, title = {The microvascular hypothesis underlying neurologic manifestations of long COVID-19 and possible therapeutic strategies.}, journal = {Cardiovascular endocrinology & metabolism}, volume = {10}, number = {4}, pages = {193-203}, pmid = {34765889}, issn = {2574-0954}, abstract = {With the ongoing distribution of the coronavirus disease (COVID) vaccines, the pandemic of our age is ending, leaving the world to deal with its well-documented aftereffects. Long COVID comprises a variety of symptoms, of which the neurological component prevails. The most permeating theory on the genesis of these symptoms builds upon the development of microvascular dysfunction similar to that seen in numerous vascular diseases such as diabetes. This can occur through the peripheral activation of angiotensin-converting enzyme 2 receptors, or through exacerbations of pro-inflammatory cytokines that can remain in circulation even after the infection diminishes. Several drugs have been identified to act on the neurovascular unit to promote repair, such as gliptins, and others. They also succeeded in improving neurologic outcome in diabetic patients. The repurposing of such drugs for treatment of long COVID-19 can possibly shorten the time to recovery of long COVID-19 syndrome.}, } @article {pmid34765348, year = {2021}, author = {Talwar, D and Kumar, S and Acharya, S and Khanna, S and Hulkoti, V}, title = {Paroxysmal Supraventricular Tachycardia and Cardiac Arrest: A Presentation of Pulmonary Embolism With Infarction as a Sequela of Long COVID Syndrome.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e18572}, pmid = {34765348}, issn = {2168-8184}, abstract = {With the emergence of diverse post-COVID sequelae, there have been reports of thromboembolic events such as stroke, myocardial infarction, and pulmonary embolism. These events have been reported after severe coronavirus disease 2019 (COVID-19) infections mostly requiring intensive care unit admissions. The findings of acute pulmonary embolism on electrocardiography are commonly sinus tachycardia and S1Q3T3. However, the presentation of pulmonary embolism with arrhythmias is rare. We report a case of a young 31-year-old female who had a history of COVID-19 with a chest computed tomography (CT) severity score of 5/25 five weeks back and presented with acute onset chest pain, breathlessness for one hour followed by collapse. She was intubated in the emergency department and managed with antiarrhythmic drugs however she went into sudden cardiorespiratory arrest and was revived with cardiopulmonary resuscitation. The patient was finally diagnosed as a case of pulmonary embolism leading to pulmonary infarction presenting as paroxysmal supraventricular tachycardia and cardiac arrest as a result of long COVID syndrome. This emphasizes the importance of routine follow-up and strict vigilance even in young patients with mild COVID-19 as it might result in serious life-threatening complications which otherwise seem to be unexpected.}, } @article {pmid34764200, year = {2021}, author = {Heightman, M and Prashar, J and Hillman, TE and Marks, M and Livingston, R and Ridsdale, HA and Bell, R and Zandi, M and McNamara, P and Chauhan, A and Denneny, E and Astin, R and Purcell, H and Attree, E and Hishmeh, L and Prescott, G and Evans, R and Mehta, P and Brennan, E and Brown, JS and Porter, J and Logan, S and Wall, E and Dehbi, HM and Cone, S and Banerjee, A}, title = {Post-COVID-19 assessment in a specialist clinical service: a 12-month, single-centre, prospective study in 1325 individuals.}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, pmid = {34764200}, issn = {2052-4439}, support = {MC_PC_20022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19 ; Delivery of Health Care ; Ethnicity ; Female ; Humans ; Male ; Minority Groups ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Post-COVID-19 complications require simultaneous characterisation and management to plan policy and health system responses. We describe the 12-month experience of the first UK dedicated post-COVID-19 clinical service to include hospitalised and non-hospitalised patients.

METHODS: In a single-centre, observational analysis, we report the demographics, symptoms, comorbidities, investigations, treatments, functional recovery, specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post-COVID-19 service between April 2020 and April 2021, comparing by referral route: posthospitalised (PH), non-hospitalised (NH) and post emergency department (PED). Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression.

RESULTS: 1325 individuals were assessed (PH: 547, 41.3%; PED: 212, 16%; NH: 566, 42.7%). Compared with the PH and PED groups, the NH group were younger (median 44.6 (35.6-52.8) years vs 58.3 (47.0-67.7) years and 48.5 (39.4-55.7) years), more likely to be female (68.2%, 43.0% and 59.9%), less likely to be of ethnic minority (30.9%, 52.7% and 41.0%) or seen later after symptom onset (median (IQR): 194 (118-298) days, 69 (51-111) days and 76 (55-128) days; all p<0.0001). All groups had similar rates of onward specialist referral (NH 18.7%, PH 16.1% and PED 18.9%, p=0.452) and were more likely to require support for breathlessness (23.7%, 5.5% and 15.1%, p<0.001) and fatigue (17.8%, 4.8% and 8.0%, p<0.001). Hospitalised patients had higher rates of pulmonary emboli, persistent lung interstitial abnormalities and other organ impairment. 716 (54.0%) individuals reported <75% optimal health (median 70%, IQR 55%-85%). Less than half of employed individuals could return to work full time at first assessment.

CONCLUSION: Post-COVID-19 symptoms were significant in PH and NH patients, with significant ongoing healthcare needs and utilisation. Trials of interventions and patient-centred pathways for diagnostic and treatment approaches are urgently required.}, } @article {pmid34763058, year = {2022}, author = {Bai, F and Tomasoni, D and Falcinella, C and Barbanotti, D and Castoldi, R and Mulè, G and Augello, M and Mondatore, D and Allegrini, M and Cona, A and Tesoro, D and Tagliaferri, G and Viganò, O and Suardi, E and Tincati, C and Beringheli, T and Varisco, B and Battistini, CL and Piscopo, K and Vegni, E and Tavelli, A and Terzoni, S and Marchetti, G and Monforte, AD}, title = {Female gender is associated with long COVID syndrome: a prospective cohort study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {28}, number = {4}, pages = {611.e9-611.e16}, pmid = {34763058}, issn = {1469-0691}, mesh = {Adult ; *COVID-19/complications/diagnosis/epidemiology ; Female ; Humans ; Male ; Prospective Studies ; Respiration, Artificial ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: We explored the association between female gender and long COVID syndrome, defined as persistence of physical and/or psychological symptoms for more than 4 weeks after recovery from acute COVID-19 disease. The secondary aim was to identify predictors of long COVID syndrome by multivariable logistic regression analysis.

METHODS: This was a single-centre prospective cohort study conducted at San Paolo Hospital in Milan, Italy. We enrolled adult patients who were evaluated at the post-COVID outpatient service of our Infectious Diseases Unit between 15 April 2020 and 15 December 2020. Participants were individuals who had clinically recovered from COVID-19 and in whom virological clearance had occurred. Previous infection by SARS-CoV-2 was microbiologically documented by positivity using a reverse-transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab. All enrolled patients underwent blood tests and a comprehensive medical examination at follow-up. Individuals were interviewed about resolved and persisting symptoms and were asked to fill in two questionnaires to allow assessment of the Hospital Anxiety and Depression symptoms (HADS) score and of the Impact of Event Scale-Revised (IES-R) score.

RESULTS: A total of 377 patients were enrolled in the study. The median time from symtpom onset to virological clerance was 44 (37-53) days. A diagnosis of long COVID syndrome was made in 260/377 (69%) patients. The most common reported symptoms were fatigue (149/377, 39.5%), exertional dyspnoea (109/377, 28.9%), musculoskeletal pain (80/377, 21.2%) and "brain fog" (76/377, 20.2%). Anxiety symptoms were ascertained in 71/377 (18.8%) individuals, whereas 40/377 (10.6%) patients presented symptoms of depression. Post-traumatic stress disorder (defined by a pathological IES-R score) was diagnosed in one-third of patients (85/275, 31%). Female gender was independently associated with long COVID syndrome at multivariable analysis (AOR 3.3 vs. males, 95% CI 1.8-6.2, p < 0.0001). Advanced age (adjusted (A)OR 1.03 for 10 years older, 95% CI 1.01-1.05, p 0.01) and active smoking (AOR 0.19 for former smokers vs. active smokers, 95% CI 0.06-0.62, p 0.002) were also associated with a higher risk of long COVID, while no association was found between severity of disease and long COVID (AOR 0.67 for continuous positive airway pressure (CPAP)/non-invasive mechanical ventilation (NIMV)/orotracheal intubation (OTI) vs. no 02 therapy, 95% CI 0.29-1.55, p 0.85).

DISCUSSION: Factors that were found to be associated with a higher risk of developing "long COVID" syndrome were female gender, older age and active smoking, but not severity of the acute disease. Individuals affected by SARS-CoV-2 infection with the aforementioned features should be early identified and involved in follow-up programmes.}, } @article {pmid34760415, year = {2021}, author = {Otsuka, Y and Tokumasu, K and Nakano, Y and Honda, H and Sakurada, Y and Sunada, N and Omura, D and Hasegawa, K and Hagiya, H and Obika, M and Ueda, K and Kataoka, H and Otsuka, F}, title = {Clinical Characteristics of Japanese Patients Who Visited a COVID-19 Aftercare Clinic for Post-Acute Sequelae of COVID-19/Long COVID.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e18568}, pmid = {34760415}, issn = {2168-8184}, abstract = {Introduction The long-term clinical course, prognosis, and optimal management of symptoms and conditions after the acute phase of coronavirus disease 2019 (COVID-19) remain to be elucidated. The purpose of this study was to clarify the characteristics of patients referred to a COVID-19 aftercare (CAC) clinic established at a tertiary academic hospital in Japan. Methods This study was a descriptive case series study. All patients who visited the CAC clinic between February 15 and September 17 in 2021 were included. Patients' background, chief complaints, and clinical courses after the onset of COVID-19 were described. Results A total of 87 Japanese patients (median age, 40.0 years; interquartile range [IQR], 26.5-53.0 years; 52.9% women) were referred to the CAC clinic. The median interval between the onset of COVID-19 and the visit to the clinic was 79.0 (IQR, 52.5-112.0) days. Referral sources were hospitals (36 patients), clinics (47 patients), a local healthcare center (3 patients), and other (1 patient). The most common chief complaint was general fatigue (50.4%) followed by dysosmia (28.7%), dysgeusia (26.4%), hair loss (18.4%), headache (17.2%), dyspnea (16.1%), and dyssomnia (13.1%). Respiratory symptoms were common in the early stages of the disease but were less common as the chief complaints when visiting the clinic. On the other hand, neurological, psychiatric, and extremity symptoms were predominant one month after the onset of COVID-19. Conclusions Regardless of the severity in the acute phase, patients visiting our CAC clinic suffered from a variety of symptoms. General physicians skilled in using a comprehensive approach would be optimal to see patients with such complex symptoms.}, } @article {pmid34756631, year = {2022}, author = {Harari, S and Ripamonti, L and Marveggio, P and Mannucci, PM}, title = {Long COVID: A patient perspective.}, journal = {European journal of internal medicine}, volume = {95}, number = {}, pages = {104-105}, pmid = {34756631}, issn = {1879-0828}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34756590, year = {2022}, author = {France, K and Glick, M}, title = {Long COVID and oral health care considerations.}, journal = {Journal of the American Dental Association (1939)}, volume = {153}, number = {2}, pages = {167-174}, pmid = {34756590}, issn = {1943-4723}, mesh = {*COVID-19/complications ; Delivery of Health Care ; Humans ; Oral Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: People who have recovered from the initial severe acute respiratory syndrome coronavirus 2 infection are at risk of developing long COVID, a prolonged suite of signs and symptoms that may interfere with daily life and the ability to undergo routine oral health care.

METHODS: The available literature on long COVID was reviewed and compiled to produce a review of the syndrome as currently understood. Articles were evaluated with a focus on how long COVID may affect the provision of oral health care and on ways in which treatment may need to be modified to best care for this vulnerable patient population.

RESULTS: Long COVID includes a wide variety of symptoms, such as fatigue, shortness of breath, chest pain, risk of developing thromboembolism, and neurologic and psychiatric complications. These symptoms may arise at various times and in a wide range of patients, and they may necessitate modification of routine oral health care interventions.

CONCLUSIONS: Recommendations for the treatment of affected people in an oral health care setting are presented, including a thorough evaluation of the patient history and current status, understanding of how related symptoms may affect oral health care interventions, and which modifications to treatment are needed to provide safe and appropriate care.

PRACTICAL IMPLICATIONS: Oral health care professionals must be aware of long COVID, an increasingly prevalent condition with a widely variable presentation and impact. Oral health care professionals should be prepared to treat these patients safely in an outpatient oral health setting.}, } @article {pmid34755940, year = {2021}, author = {Marone Diop, I and Kokkinakis, I and Wenker Dabiri, C and De Vallière, S and Cornuz, J and Favrat, B}, title = {[Practical management of long Covid disease in outpatients: illustration by clinical cases].}, journal = {Revue medicale suisse}, volume = {17}, number = {758}, pages = {1915-1921}, pmid = {34755940}, issn = {1660-9379}, mesh = {*COVID-19/complications ; Humans ; *Outpatients ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 pandemic has caused an unprecedented global public health crisis. The term long Covid is used to describe diverse and heterogeneous symptoms that persist more than 4 weeks after infection with an estimated incidence of 10-40%, which varies between studies. The principal characteristics of long Covid are fluctuating symptoms of prolonged duration affecting multiple organs, such as fatigue, dyspnea, cough, anosmia, dysgeusia, chest pain, palpitations, headache, myalgia, cognitive and gastrointestinal disorders. Contributing factors, possible pathophysiological explanations and international recommendations can help in the management of the disease in the outpatient setting. Biopsychosocial and multidisciplinary management in primary care medicine is essential.}, } @article {pmid34753712, year = {2021}, author = {Banerjee, A}, title = {Long covid: new wine in need of new bottles.}, journal = {BMJ (Clinical research ed.)}, volume = {375}, number = {}, pages = {n2736}, doi = {10.1136/bmj.n2736}, pmid = {34753712}, issn = {1756-1833}, mesh = {Biomedical Research/*trends ; COVID-19/*complications ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34752489, year = {2021}, author = {Fowler-Davis, S and Platts, K and Thelwell, M and Woodward, A and Harrop, D}, title = {A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long Covid?.}, journal = {PloS one}, volume = {16}, number = {11}, pages = {e0259533}, pmid = {34752489}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/complications/epidemiology ; *Fatigue/therapy/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Fatigue syndromes have been widely observed following post-viral infection and are being recognised because of Covid19. Interventions used to treat and manage fatigue have been widely researched and this study aims to synthesise the literature associated with fatigue interventions to investigate the outcomes that may be applicable to 'long Covid'.

METHOD: The study was registered with PROSPERO (CRD42020214209) in October 2020 and five electronic databases were searched. Papers were screened, critically appraised and data extracted from studies that reported outcomes of fatigue interventions for post-viral syndromes. The narrative synthesis includes statistical analysis associated with effectiveness and then identifies the characteristics of the interventions, including identification of transferable learning for the treatment of fatigue in long Covid. An expert panel supported critical appraisal and data synthesis.

RESULTS: Over 7,000 research papers revealed a diverse range of interventions and fatigue outcome measures. Forty papers were selected for data extraction after final screening. The effectiveness of all interventions was assessed according to mean differences (MD) in measured fatigue severity between each experimental group and a control following the intervention, as well as standardised mean differences as an overall measure of effect size. Analyses identified a range of effects-from most effective MD -39.0 [95% CI -51.8 to -26.2] to least effective MD 42.28 [95% CI 33.23 to 51.34]-across a range of interventions implemented with people suffering varying levels of fatigue severity. Interventions were multimodal with a range of supportive therapeutic methods and varied in intensity and requirements of the participants. Those in western medical systems tended to be based on self- management and education principles (i.e., group cognitive behavioural therapy (CBT).

CONCLUSION: Findings suggest that the research is highly focussed on a narrow participant demographic and relatively few methods are effective in managing fatigue symptoms. Selected literature reported complex interventions using self-rating fatigue scales that report effect. Synthesis suggests that long Covid fatigue management may be beneficial when a) physical and psychological support, is delivered in groups where people can plan their functional response to fatigue; and b) where strengthening rather than endurance is used to prevent deconditioning; and c) where fatigue is regarded in the context of an individual's lifestyle and home-based activities are used.}, } @article {pmid34750595, year = {2022}, author = {García-Saugar, M and Jaén-Jover, C and Hernández-Sánchez, S and Poveda-Pagán, EJ and Lozano-Quijada, C}, title = {[Recommendations for outpatient respiratory rehabilitation of long COVID patients].}, journal = {Anales del sistema sanitario de Navarra}, volume = {45}, number = {1}, pages = {}, pmid = {34750595}, issn = {2340-3527}, mesh = {*COVID-19/complications ; Humans ; Outpatients ; Physical Therapy Modalities ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The appearance of COVID-19 has been a problem for public health on a global scale, putting pressure on health care systems. The after-effects of this illness have highlighted the importance of rehabilitation in long COVID patients involv-ing different health professionals. The treatment of the respiratory after-effects of this disease in an outpatient setting is a specialized field. It is appropriate to offer a series of practical recommendations of cardio-respiratory rehabilitation that are helpful to the professionals involved in the after-effects when ending hospitalisation. This review of the literature includes ten key aspects of respiratory physiotherapy that range from assessment, parameters to monitor, signs of alarm and respiratory rehabilitation techniques and other exercises for this population.}, } @article {pmid34748955, year = {2021}, author = {Barber, MS and Barrett, R and Bradley, RD and Walker, E}, title = {A naturopathic treatment approach for mild and moderate COVID-19: A retrospective chart review.}, journal = {Complementary therapies in medicine}, volume = {63}, number = {}, pages = {102788}, pmid = {34748955}, issn = {1873-6963}, mesh = {*COVID-19/complications ; COVID-19 Vaccines ; Humans ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to significant morbidity and mortality. Although COVID-19 vaccination is available, therapeutic options are still needed. The goal of the present manuscript is to report on a treatment strategy used in a naturopathic medical practice for mild and moderate COVID-19.

DESIGN: A retrospective chart review was conducted of 30 consecutive patients diagnosed with mild and moderate COVID-19 who were provided multi-nutrient, herbal, and probiotic treatment in a rural, out-patient, naturopathic primary care setting.

MAIN OUTCOMES MEASURES: The primary outcome was treatment safety; secondary outcomes included changes in symptoms, progression to severe COVID-19, incidence of long COVID, and recovery time.

RESULTS: No side effects or adverse events were reported from treatment and all patients experienced resolution of symptoms presumed to be associated with COVID-19 infection. One patient who had been ill for 28 days prior to presentation was hospitalized. Five patients had an illness duration of more than one month. Time to treatment was correlated with duration of illness post-treatment (r = 0.63, p < 0.001) and more symptoms at presentation was correlated with a longer duration of illness (r = 0.52, p < 0.01).

CONCLUSIONS: In this retrospective chart review, a multi-nutrient, herbal, and probiotic therapeutic approach for mild and moderate COVID-19 appeared to be well-tolerated. Delay in seeking treatment after symptom onset, as well as more symptoms at presentation, were correlated with a longer duration of illness. This treatment strategy may have clinical benefit, warranting prospective clinical trials with confirmed COVID-19 cases.}, } @article {pmid34747982, year = {2022}, author = {Matta, J and Wiernik, E and Robineau, O and Carrat, F and Touvier, M and Severi, G and de Lamballerie, X and Blanché, H and Deleuze, JF and Gouraud, C and Hoertel, N and Ranque, B and Goldberg, M and Zins, M and Lemogne, C and , }, title = {Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic.}, journal = {JAMA internal medicine}, volume = {182}, number = {1}, pages = {19-25}, pmid = {34747982}, issn = {2168-6114}, mesh = {Adult ; COVID-19/blood/*diagnosis/epidemiology ; COVID-19 Serological Testing/methods/*standards/statistics & numerical data ; Cross-Sectional Studies ; Female ; France/epidemiology ; Humans ; Male ; Middle Aged ; *Self Report ; Surveys and Questionnaires ; *Syndrome ; }, abstract = {IMPORTANCE: After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors.

OBJECTIVE: To examine the associations of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms (eg, fatigue, breathlessness, or impaired attention) in the general population during the COVID-19 pandemic.

Participants in this cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, an enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Between December 2020 and January 2021, the participants reported whether they believed they had experienced COVID-19 infection and had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants who reported having an initial COVID-19 infection only after completing the serology test were excluded.

MAIN OUTCOMES AND MEASURES: Logistic regressions for each persistent symptom as the outcome were computed in models including both self-reported COVID-19 infection and serology test results and adjusting for age, sex, income, and educational level.

RESULTS: Of 35 852 volunteers invited to participate in the study, 26 823 (74.8%) with complete data were included in the present study (mean [SD] age, 49.4 [12.9] years; 13 731 women [51.2%]). Self-reported infection was positively associated with persistent physical symptoms, with odds ratios ranging from 1.39 (95% CI, 1.03-1.86) to 16.37 (95% CI, 10.21-26.24) except for hearing impairment (odds ratio, 1.45; 95% CI, 0.82-2.55) and sleep problems (odds ratio, 1.14; 95% CI, 0.89-1.46). A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66-4.46), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection. Further adjusting for self-rated health or depressive symptoms yielded similar results. There was no significant interaction between belief and serology test results.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection. Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus. A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to "long COVID."}, } @article {pmid34747740, year = {2021}, author = {Rajkumar Tripathi, AK and Pinto, LM}, title = {Long COVID: "And the fire rages on".}, journal = {Lung India : official organ of Indian Chest Society}, volume = {38}, number = {6}, pages = {564-570}, pmid = {34747740}, issn = {0970-2113}, abstract = {With the increasing cohort of COVID-19 survivors worldwide, we now realize the proportionate rise in post-COVID-19 syndrome. In this review article, we try to define, summarize, and classify this syndrome systematically. This would help clinicians to identify and manage this condition more efficiently. We propose a tool kit that might be useful in recording follow-up data of COVID-19 survivors.}, } @article {pmid34746909, year = {2021}, author = {Stewart, S and Newson, L and Briggs, TA and Grammatopoulos, D and Young, L and Gill, P}, title = {Long COVID risk - a signal to address sex hormones and women's health.}, journal = {The Lancet regional health. Europe}, volume = {11}, number = {}, pages = {100242}, pmid = {34746909}, issn = {2666-7762}, } @article {pmid34745122, year = {2021}, author = {van de Ven, K and van Dijken, H and Wijsman, L and Gomersbach, A and Schouten, T and Kool, J and Lenz, S and Roholl, P and Meijer, A and van Kasteren, PB and de Jonge, J}, title = {Pathology and Immunity After SARS-CoV-2 Infection in Male Ferrets Is Affected by Age and Inoculation Route.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {750229}, pmid = {34745122}, issn = {1664-3224}, mesh = {Administration, Intranasal ; Age Factors ; Animals ; Asymptomatic Diseases ; Bronchi/*pathology ; COVID-19/*complications/*immunology ; Disease Models, Animal ; Ferrets/*immunology/virology ; Humans ; Hyperplasia ; Immunity, Cellular ; Immunity, Humoral ; Injection, Intratympanic ; Male ; SARS-CoV-2/*physiology ; Virus Internalization ; Post-Acute COVID-19 Syndrome ; }, abstract = {Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nasal turbinates was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.}, } @article {pmid34742667, year = {2022}, author = {Heo, S and Young, DC and Safirstein, J and Bourque, B and Antell, MH and Diloreto, S and Rotolo, SM}, title = {Mental status changes during elexacaftor/tezacaftor / ivacaftor therapy.}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {21}, number = {2}, pages = {339-343}, doi = {10.1016/j.jcf.2021.10.002}, pmid = {34742667}, issn = {1873-5010}, mesh = {*Affect/drug effects ; Aminophenols ; Benzodioxoles ; Chloride Channel Agonists ; *Cystic Fibrosis/drug therapy/genetics ; *Cystic Fibrosis Transmembrane Conductance Regulator/drug effects ; Drug Combinations ; Humans ; Indoles ; Mental Fatigue ; Pyrazoles ; Pyridines ; Pyrrolidines ; Quinolones ; Somatoform Disorders ; }, abstract = {Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta) is the newest Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drug approved by the Food and Drug Administration. Post-marketing reports with earlier CFTR modulators suggest these medications can impact mood, and in clinical trials an adverse effect of headache was reported with all currently approved CFTR modulators. However, there are no other documented reports of mental status changes during clinical trials or in post-marketing reports with elexacaftor/tezacaftor/ivacaftor. In this case series, we describe 6 patients who reported "mental fogginess" or other mental status changes shortly after initiation of this drug. The mechanism of this patient-reported side effect is still unclear. All patients noticed a change within the first 3 months of therapy. The management differed in each case, with all four cystic fibrosis (CF) care teams utilizing a patient-centered decision-making approach to address this concern.}, } @article {pmid34738307, year = {2022}, author = {Fogarty, H and Karampini, E and O'Donnell, AS and Ward, SE and O'Sullivan, JM and O'Donnell, JS and , }, title = {Persistent endotheliopathy in the pathogenesis of long COVID syndrome - Reply to comment from von Meijenfeldt et al.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {20}, number = {1}, pages = {270-271}, pmid = {34738307}, issn = {1538-7836}, mesh = {*COVID-19/complications ; Endothelial Cells ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34732518, year = {2021}, author = {Buttery, S and Philip, KEJ and Williams, P and Fallas, A and West, B and Cumella, A and Cheung, C and Walker, S and Quint, JK and Polkey, MI and Hopkinson, NS}, title = {Patient symptoms and experience following COVID-19: results from a UK-wide survey.}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, pmid = {34732518}, issn = {2052-4439}, mesh = {*COVID-19/complications ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Surveys and Questionnaires ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To investigate the experience of people who continue to be unwell after acute COVID-19, often referred to as 'long COVID', both in terms of their symptoms and their interactions with healthcare.

DESIGN: We conducted a mixed-methods analysis of responses to a survey accessed through a UK online post-COVID-19 support and information hub, between April and December 2020, about people's experiences after having acute COVID-19.

PARTICIPANTS: 3290 respondents, 78% female, 92.1% white ethnicity and median age range 45-54 years; 12.7% had been hospitalised. 494(16.5%) completed the survey between 4 and 8 weeks of the onset of their symptoms, 641(21.4%) between 8 and 12 weeks and 1865 (62.1%) >12 weeks after.

RESULTS: The ongoing symptoms most frequently reported were: breathing problems (92.1%), fatigue (83.3%), muscle weakness or joint stiffness (50.6%), sleep disturbances (46.2%), problems with mental abilities (45.9%), changes in mood, including anxiety and depression (43.1%) and cough (42.3%). Symptoms did not appear to be related to the severity of the acute illness or to the presence of pre-existing medical conditions. Analysis of free-text responses revealed three main themes: (1) experience of living with COVID-19: physical and psychological symptoms that fluctuate unpredictably; (2) interactions with healthcare that were unsatisfactory; (3) implications for the future: their own condition, society and the healthcare system, and the need for research CONCLUSION: Consideration of patient perspectives and experiences will assist in the planning of services to address problems persisting in people who remain symptomatic after the acute phase of COVID-19.}, } @article {pmid34731533, year = {2022}, author = {von Meijenfeldt, FA and Havervall, S and Adelmeijer, J and Thalin, C and Lisman, T}, title = {Persistent endotheliopathy in the pathogenesis of long COVID syndrome: Comment from von Meijenfeldt et al.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {20}, number = {1}, pages = {267-269}, pmid = {34731533}, issn = {1538-7836}, mesh = {*COVID-19/complications ; Endothelial Cells/pathology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34730322, year = {2021}, author = {Goel, N and Goyal, N and Nagaraja, R and Kumar, R}, title = {Systemic corticosteroids for management of 'long-COVID': an evaluation after 3 months of treatment.}, journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace}, volume = {92}, number = {2}, pages = {}, doi = {10.4081/monaldi.2021.1981}, pmid = {34730322}, issn = {2532-5264}, mesh = {Adrenal Cortex Hormones/therapeutic use ; *COVID-19/complications ; Dyspnea ; Humans ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Some patients even 4 weeks after Corona Virus Disease 2019 (COVID-19) remain to be symptomatic and are known as "long-COVID". In the present study we performed the follow up evaluation at 3 months of long-COVID patients, after treatment with systemic steroids. During the study duration, out of the 4,542 patients managed in the outpatient department of the particular unit, there were 49 patients of Long-COVID. The patients having abnormal computed tomography (CT) alongwith resting hypoxia or exertional desaturation were treated with systemic steroid (deflazacort) in tapering doses for 8-10 weeks. We retrospectively analysed the clinical and radiological findings of these patients at first presentation and at about 3 months of follow up visit. On follow up, all the 49 long-COVID patients showed improvement. The occurrence of breathlessness decreased from 91.83% to 44.89% (p<0.001) and cough from 77.55% to 8.16% (p<0.001). Twenty-four patients were prescribed systemic steroids. Out of these, nearly 58% patients had MMRC grade 4 breathlessness, which decreased to < 2 MMRC in about 86% of these patients. MMRC grade (median) decreased from 3 to 1 (p<0.001). Majority of patients who were tachypnoeic and hypoxic at rest (n=7) showed improvement (71%), post-treatment with corticosteroids. Occurrence of normal chest X-ray increased from 12% to 71% (p<0.001). All these patients had abnormal CT thorax initially, and post-treatment 25% had normal CT thorax. Hence, we conclude that systemic steroids are helpful in hastening recovery of select subset of long-COVID patients. Simultaneously, we should be cautious of immunosuppressive effects of steroids like tuberculosis reactivation, especially in tuberculosis endemic countries. These findings have therapeutic implications and may serve as guidance for future approach to the management of 'long-COVID' with pulmonary sequalae.}, } @article {pmid34729561, year = {2021}, author = {Wang, JY and Zhang, W and Roehrl, MW and Roehrl, VB and Roehrl, MH}, title = {An Autoantigen Profile from Jurkat T-Lymphoblasts Provides a Molecular Guide for Investigating Autoimmune Sequelae of COVID-19.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {34729561}, issn = {2692-8205}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R21 CA251992/CA/NCI NIH HHS/United States ; }, abstract = {In order to understand autoimmune phenomena contributing to the pathophysiology of COVID-19 and post-COVID syndrome, we have been profiling autoantigens (autoAgs) from various cell types. Although cells share numerous autoAgs, each cell type gives rise to unique COVID-altered autoAg candidates, which may explain the wide range of symptoms experienced by patients with autoimmune sequelae of SARS-CoV-2 infection. Based on the unifying property of affinity between autoantigens (autoAgs) and the glycosaminoglycan dermatan sulfate (DS), this paper reports 140 candidate autoAgs identified from proteome extracts of human Jurkat T-cells, of which at least 105 (75%) are known targets of autoantibodies. Comparison with currently available multi-omic COVID-19 data shows that 125 (89%) of DS-affinity proteins are altered at protein and/or RNA levels in SARS-CoV-2-infected cells or patients, with at least 94 being known autoAgs in a wide spectrum of autoimmune diseases and cancer. Protein alterations by ubiquitination and phosphorylation in the viral infection are major contributors of autoAgs. The autoAg protein network is significantly associated with cellular response to stress, apoptosis, RNA metabolism, mRNA processing and translation, protein folding and processing, chromosome organization, cell cycle, and muscle contraction. The autoAgs include clusters of histones, CCT/TriC chaperonin, DNA replication licensing factors, proteasome and ribosome proteins, heat shock proteins, serine/arginine-rich splicing factors, 14-3-3 proteins, and cytoskeletal proteins. AutoAgs such as LCP1 and NACA that are altered in the T cells of COVID patients may provide insight into T-cell responses in the viral infection and merit further study. The autoantigen-ome from this study contributes to a comprehensive molecular map for investigating acute, subacute, and chronic autoimmune disorders caused by SARS-CoV-2.}, } @article {pmid34729556, year = {2021}, author = {Klein, R and Soung, A and Sissoko, C and Nordvig, A and Canoll, P and Mariani, M and Jiang, X and Bricker, T and Goldman, J and Rosoklija, G and Arango, V and Underwood, M and Mann, JJ and Boon, A and Dowrk, A and Boldrini, M}, title = {COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {34729556}, issn = {2693-5015}, support = {U01 NS090415/NS/NINDS NIH HHS/United States ; R01 MH083862/MH/NIMH NIH HHS/United States ; R01 MH125030/MH/NIMH NIH HHS/United States ; R01 MH098786/MH/NIMH NIH HHS/United States ; R01 MH064168/MH/NIMH NIH HHS/United States ; U01 AI151810/AI/NIAID NIH HHS/United States ; R56 AG063372/AG/NIA NIH HHS/United States ; R35 NS122310/NS/NINDS NIH HHS/United States ; P30 AG066462/AG/NIA NIH HHS/United States ; P50 MH090964/MH/NIMH NIH HHS/United States ; R21 AI164769/AI/NIAID NIH HHS/United States ; R01 MH040210/MH/NIMH NIH HHS/United States ; }, abstract = {Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness [1-4] . Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous system symptoms remain largely unknown.In an established hamster model of intranasal infection with SARS-CoV-2 [5] , and patients deceased from COVID-19, we report a lack of viral neuroinvasion despite aberrant BBB permeability, microglial activation, and brain expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the inferior olivary nucleus of the medulla, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uremia or trauma. In the hippocampus dentate gyrus of both COVID-19 hamsters and humans, fewer cells expressed doublecortin, a marker of neuroblasts and immature neurons.Despite absence of viral neurotropism, we find SARS-CoV-2-induced inflammation, and hypoxia in humans, affect brain regions essential for fine motor function, learning, memory, and emotional responses, and result in loss of adult hippocampal neurogenesis. Neuroinflammation could affect cognition and behaviour via disruption of brain vasculature integrity, neurotransmission, and neurogenesis, acute effects that may persist in COVID-19 survivors with long-COVID symptoms.}, } @article {pmid34729276, year = {2021}, author = {Varanasi, S and Sathyamoorthy, M and Chamakura, S and Shah, SA}, title = {Management of Long-COVID Postural Orthostatic Tachycardia Syndrome With Enhanced External Counterpulsation.}, journal = {Cureus}, volume = {13}, number = {9}, pages = {e18398}, pmid = {34729276}, issn = {2168-8184}, abstract = {A growing number of patients diagnosed with COVID-19 disease have been reported to have postural orthostatic tachycardia syndrome (POTS) after the acute phase. A 57-year-old female was diagnosed with COVID-19 in December 2020. As a result of her acute illness, she was hospitalized for COVID pneumonia and respiratory failure, followed by stays at an acute care facility and home rehabilitation center. After the acute phase, the patient was diagnosed with long-COVID-19-associated POTS with symptoms such as fatigue, "brain fog," and dyspnea. The patient was referred to an enhanced external counterpulsation (EECP) treatment center and underwent 15, one-hour sessions over three weeks. Upon completion of therapy, the patient reported improvements with "brain fog" and the ability to perform activities of daily living. Her Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue score was reduced by three points, six-minute walk distance increased by 85 feet, and Duke Activity Status Index (DASI) improved by over 15 points. EECP therapy was chosen due to the overlap in underlying pathology driving POTS and the mechanisms of action of EECP. This report is the first case of using EECP for the successful management of COVID-19-associated POTS and warrants further trials.}, } @article {pmid34726085, year = {2021}, author = {Lindsay, RK and Wilson, JJ and Trott, M and Olanrewaju, O and Tully, MA and López-Sánchez, GF and Shin, JI and Pizzol, D and Allen, P and Butler, LT and Barnett, Y and Smith, L}, title = {What are the recommendations for returning athletes who have experienced long term COVID-19 symptoms?.}, journal = {Annals of medicine}, volume = {53}, number = {1}, pages = {1935-1944}, pmid = {34726085}, issn = {1365-2060}, mesh = {*Athletes ; Athletic Performance/*physiology ; COVID-19/*complications/physiopathology/rehabilitation ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {Currently, there is limited research reporting the symptoms of long COVID among athletes, and the recommendations for athletes returning to competition/training who have experienced long COVID symptoms. Therefore, the aim of this systematic review is to synthesise the recommendations for returning athletes who have experienced long COVID symptoms. The protocol was registered in PROSPERO under CRD42021265939. Two authors searched the electronic databases PubMed, Embase, Scopus, the Cochrane Library, Web of Science, CINAHL, PsycINFO, and SPORTDiscus from August 2019-July 2021. Search terms included words related to "long COVID", "athlete" and "return". Data extraction was completed for each study by two independent investigators for: (1) first author name; (2) year of publication; (3) journal; (4) Definition of athlete (i.e. elite or non-elite) (5) Recommendations reported. A total of 220 records were found. Following title and abstract screening, 61 studies were eligible for full text screening. Overall, no studies, commentaries, editorials or reviews provided specific recommendations for "long COVID" defined as COVID-19 signs and symptoms lasting for over 4 weeks as a result of COVID-19 infection. In addition, we found no studies which reported symptoms of athletes suffering from long COVID. Despite the lack of evidence, we did find eight separate professional recommendations for managing "long-term effects" and "ongoing" or "prolonged" symptoms and COVID-19 complications among athletes. Practitioners should be aware of both mental and physical symptoms of long COVID, and additional considerations may be required for athletes who have undergone intensive care. The present review provides a list of recommendations based on existing literature that may be followed and implemented for returning athletes.Key MessagesFurther research, including longitudinal research of athletes who have tested positive for COVID-19, is required to develop evidenced-based guidelines for athletes with ongoing COVID-19 symptoms.Prior to returning to play after COVID-19 infection, a thorough medical history, physical and psychological examination should be conducted by a medical professional.Athletes should continue to monitor and record their own physical and psychological markers of health.}, } @article {pmid34723680, year = {2021}, author = {Gurdasani, D and Bhatt, S and Costello, A and Denaxas, S and Flaxman, S and Greenhalgh, T and Griffin, S and Hyde, Z and Katzourakis, A and McKee, M and Michie, S and Ratmann, O and Reicher, S and Scally, G and Tomlinson, C and Yates, C and Ziauddeen, H and Pagel, C}, title = {Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis.}, journal = {Journal of the Royal Society of Medicine}, volume = {114}, number = {11}, pages = {513-524}, pmid = {34723680}, issn = {1758-1095}, support = {MR/K006584/1/MRC_/Medical Research Council/United Kingdom ; MR/V038109/1/MRC_/Medical Research Council/United Kingdom ; MR/S003711/1/MRC_/Medical Research Council/United Kingdom ; MR/R015600/1/MRC_/Medical Research Council/United Kingdom ; MR/S003711/2/MRC_/Medical Research Council/United Kingdom ; MC_PC_19012/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adolescent Health ; Age Factors ; COVID-19/complications/mortality/*prevention & control/therapy ; *COVID-19 Vaccines/adverse effects ; Child ; Child Health ; England ; Female ; *Hospitalization ; Humans ; Incidence ; *Intensive Care Units ; Male ; Myocarditis/etiology ; *Public Health ; Risk ; SARS-CoV-2 ; *Severity of Illness Index ; Treatment Outcome ; *Vaccination/adverse effects ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To offer a quantitative risk-benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England.

SETTING: England.

DESIGN: Following the risk-benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12-17 in England. We then used these rates alongside a range of estimates for incidence of long COVID, vaccine efficacy and vaccine-induced myocarditis, to estimate hospital and Intensive Care Unit admissions, deaths and cases of long COVID over a period of 16 weeks under assumptions of high and low case incidence.

PARTICIPANTS: All 12-17 year olds with a record of confirmed SARS-CoV-2 infection in England between 1 July 2020 and 31 March 2021 using national linked electronic health records, accessed through the British Heart Foundation Data Science Centre.

MAIN OUTCOME MEASURES: Hospitalisations, Intensive Care Unit admissions, deaths and cases of long COVID averted by vaccinating all 12-17 year olds in England over a 16-week period under different estimates of future case incidence.

RESULTS: At high future case incidence of 1000/100,000 population/week over 16 weeks, vaccination could avert 4430 hospital admissions and 36 deaths over 16 weeks. At the low incidence of 50/100,000/week, vaccination could avert 70 hospital admissions and two deaths over 16 weeks. The benefit of vaccination in terms of hospitalisations in adolescents outweighs risks unless case rates are sustainably very low (below 30/100,000 teenagers/week). Benefit of vaccination exists at any case rate for the outcomes of death and long COVID, since neither have been associated with vaccination to date.

CONCLUSIONS: Given the current (as at 15 September 2021) high case rates (680/100,000 population/week in 10-19 year olds) in England, our findings support vaccination of adolescents against SARS-CoV2.}, } @article {pmid34721055, year = {2021}, author = {Hebbard, C and Lee, B and Katare, R and Garikipati, VNS}, title = {Diabetes, Heart Failure, and COVID-19: An Update.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {706185}, pmid = {34721055}, issn = {1664-042X}, abstract = {The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the WHO in March 2020. As of August 2021, more than 220 countries have been affected, accounting for 211,844,613 confirmed cases and 4,432,802 deaths worldwide. A new delta variant wave is sweeping through the globe. While previous reports consistently have demonstrated worse prognoses for patients with existing cardiovascular disease than for those without, new studies are showing a possible link between SARS-CoV-2 infection and an increased incidence of new-onset heart disease and diabetes, regardless of disease severity. If this trend is true, with hundreds of millions infected, the disease burden could portend a potentially troubling increase in heart disease and diabetes in the future. Focusing on heart failure in this review, we discuss the current data at the intersection of COVID, heart failure, and diabetes, from clinical findings to potential mechanisms of how SARS-CoV-2 infection could increase the incidence of those pathologies. Additionally, we posit questions for future research areas regarding the significance for patient care.}, } @article {pmid34720198, year = {2021}, author = {Zepp, F and Knuf, M}, title = {[Coronavirus disease 2019 in childhood and adolescence].}, journal = {Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde}, volume = {169}, number = {11}, pages = {1010-1033}, pmid = {34720198}, issn = {0026-9298}, abstract = {The coronavirus disease 2019 (COVID‑19) mostly occurs in children and adolescents as an asymptomatic infection. The course of the disease is usually mild or moderate. The estimated seroprevalence in Germany before the start of the vaccination program in children and adolescents was > 10%. Individual risk factors for a severe course are known. The COVID‑19-associated pediatric inflammatory multisystem syndrome (PIMS) is a very rare and severe disease with a favorable prognosis if diagnosed early and treated appropriately. The data situation on long-COVID syndrome in children and adolescents is still insufficiently defined and the incidence is not known. The primary source of infections in children and adolescents are household contacts. Transmission in school settings and other day care facilities play a subordinate role, at least in Germany.Two mRNA vaccines are currently approved in Europe for the prevention of COVID‑19 in children and adolescents above the age of 12 years. Except for the very rare occurrence of pericarditis/myocarditis in temporal association with the vaccination, especially in young men, the COVID‑19 vaccines are considered effective and safe in the age group 12-17 years. The Standing Vaccination Commission (STIKO) issued a vaccination recommendation for all 12-17-year-olds on 19 August 2021.}, } @article {pmid34719599, year = {2021}, author = {Naik, S and Haldar, SN and Soneja, M and Mundadan, NG and Garg, P and Mittal, A and Desai, D and Trilangi, PK and Chakraborty, S and Begam, NN and Bhattacharya, B and Maher, G and Mahishi, N and Rajanna, C and Kumar, SS and Arunan, B and Kirtana, J and Gupta, A and Patidar, D and Kodan, P and Sethi, P and Ray, A and Jorwal, P and Kumar, A and Nischal, N and Sinha, S and Biswas, A and Wig, N}, title = {Post COVID-19 sequelae: A prospective observational study from Northern India.}, journal = {Drug discoveries & therapeutics}, volume = {15}, number = {5}, pages = {254-260}, doi = {10.5582/ddt.2021.01093}, pmid = {34719599}, issn = {1881-784X}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; COVID-19/*complications/epidemiology/etiology/pathology ; Cough/epidemiology/etiology ; Dyspnea/epidemiology/etiology ; Fatigue/epidemiology/etiology ; Female ; Humans ; India/epidemiology ; Male ; Middle Aged ; Myalgia/epidemiology/etiology ; Prospective Studies ; Risk Factors ; Sleep Initiation and Maintenance Disorders/epidemiology/etiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.}, } @article {pmid34622141, year = {2021}, author = {McCarron, M and Allen, A and McCausland, D and Haigh, M and Luus, R and Bavussantakath, FR and Sheerin, F and Mulryan, N and Burke, E and McGlinchey, E and Flannery, F and McCallion, P}, title = {The impact of COVID-19 on people ageing with an intellectual disability in Ireland: Protocol for a follow-up survey.}, journal = {HRB open research}, volume = {4}, number = {}, pages = {95}, pmid = {34622141}, issn = {2515-4826}, abstract = {Background: The COVID-19 pandemic and associated lockdowns have had a dramatic impact on many people, but individuals with an intellectual disability, given the prevalence of congregate living and high levels of co-morbid conditions, may be particularly vulnerable at this time. A prior initial survey of participants of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) found that, despite a majority of participants being tested, only a small proportion had tested positive for COVID-19. Furthermore, despite some reporting positive aspects to the lockdown, a similar proportion were experiencing stress or anxiety during the pandemic. The pandemic and lockdowns have continued, and it is possible that experiences and consequences have changed over time. Aim: To explore over time and in greater depth the impact of COVID-19 and associated lockdowns and to further establish rates of infection, rates of vaccination and participants' experiences. Methods: A structured questionnaire for people with intellectual disability participating in the IDS-TILDA longitudinal study, to be administered by telephone/video in summer 2021. Where participants are unable to respond independently, a proxy respondent will be invited to either assist the participant or answer questions on their behalf. This questionnaire will include questions from the first COVID-19 questionnaire, with extra questions assessing "long COVID" (i.e. COVID-19 lasting for 12 weeks or longer), infection control behaviours, changes in mental health, social contacts and loneliness, frailty, healthcare, and incidence of vaccination. Impact: The results of this survey will be used to inform healthcare provision for people with intellectual disability during the latter stages of the lockdown and into the future.}, } @article {pmid34718113, year = {2022}, author = {Hugon, J}, title = {Long-COVID: Cognitive deficits (brain fog) and brain lesions in non-hospitalized patients.}, journal = {Presse medicale (Paris, France : 1983)}, volume = {51}, number = {2}, pages = {104090}, pmid = {34718113}, issn = {2213-0276}, mesh = {Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19/complications ; *Cognition Disorders/etiology ; *Nervous System Diseases ; Brain/diagnostic imaging ; Cognition ; }, } @article {pmid34717691, year = {2021}, author = {Crispo, A and Bimonte, S and Porciello, G and Forte, CA and Cuomo, G and Montagnese, C and Prete, M and Grimaldi, M and Celentano, E and Amore, A and de Blasio, E and Pentimalli, F and Giordano, A and Botti, G and Baglio, G and Sileri, P and Cascella, M and Cuomo, A}, title = {Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors.}, journal = {Infectious agents and cancer}, volume = {16}, number = {1}, pages = {62}, pmid = {34717691}, issn = {1750-9378}, abstract = {SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.}, } @article {pmid34717676, year = {2021}, author = {Nunn, AVW and Guy, GW and Botchway, SW and Bell, JD}, title = {SARS-CoV-2 and EBV; the cost of a second mitochondrial "whammy"?.}, journal = {Immunity & ageing : I & A}, volume = {18}, number = {1}, pages = {40}, pmid = {34717676}, issn = {1742-4933}, support = {the guy foundation//the guy foundation/ ; }, abstract = {We, and others, have suggested that as the SARS-CoV-2 virus may modulate mitochondrial function, good mitochondrial reserve and health could be key in determining disease severity when exposed to this virus, as the immune system itself is dependent on this organelle's function. With the recent publication of a paper showing that long COVID could be associated with the reactivation of the Epstein Barr Virus, which is well known to manipulate mitochondria, we suggest that this could represent a second mitochondrial "whammy" that might support the mitochondrial hypothesis underlying COVID-19 severity and potentially, the occurrence of longer-term symptoms. As mitochondrial function declines with age, this could be an important factor in why older populations are more susceptible. Key factors which ensure optimal mitochondrial health are generally those that ensure healthy ageing, such as a good lifestyle with plenty of physical activity. The ability of viruses to manipulate mitochondrial function is well described, and it is now also thought that for evolutionary reasons, they also manipulate the ageing process. Given that slowing the ageing process could well be linked to better economic outcomes, the link between mitochondrial health, economics, COVID-19 and other viruses, as well as lifestyle, needs to be considered.}, } @article {pmid34716898, year = {2022}, author = {Moradpour, G and Amini, M and Moeinvaziri, N and Hosseini, SV and Rajabi, S and Clark, CCT and Hosseini, B and Vafa, L and Haghighat, N}, title = {Bariatric Surgery and COVID-19: What We Have Learned from the Pandemic in Iran: a Retrospective Observational Cohort Study.}, journal = {Obesity surgery}, volume = {32}, number = {1}, pages = {18-25}, pmid = {34716898}, issn = {1708-0428}, mesh = {*Bariatric Surgery ; *COVID-19 ; Humans ; Iran/epidemiology ; *Obesity, Morbid/surgery ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {PURPOSE: Little is known about the symptoms of coronavirus disease 2019 (COVID-19) on patients with morbid obesity following bariatric surgery (BS) in Iran. Thus, we sought to investigate the symptoms and effect of COVID-19 in patients with morbid obesity following, or candidates for, BS in Iran.

MATERIALS AND METHODS: In this retrospective observational cohort study, we enrolled 236 morbid obese patients following (surgical group) or candidates (nonsurgical group) for bariatric surgery. Demographics, probable COVID-19 incidence, acute and persistent COVID-19 symptoms, and clinical outcome parameters of bariatric patients and candidates for BS were compared. The incidence of probable COVID-19 was assessed including the clinical definition of probable case, according to World Health Organization criteria.

RESULTS: The incidence of probable COVID-19 among surgical and nonsurgical groups was significantly different (20.6% vs 26.08%, respectively, p = 0.046). The probable case of surgical patients had a shorter length of symptoms and hospitalization duration, and a lower proportion of admission in ICUs and hospitals with respect to nonsurgical patients (p < 0.001). Surgical patients had a greater prevalence of persistent symptoms including anorexia, food intolerance, and anosmia-hyposmia than nonsurgical patients. Moreover, surgical patients with probable COVID-19 had a significantly higher proportion of diabetic patients than surgical patients without probable COVID-19 (20% vs 9.3%).

CONCLUSION: These findings highlight the need to evaluate the persistent symptoms of COVID-19 and the importance of nutritional support for at least several weeks after COVID-19 symptom onset. Moreover, it seems that COVID-19 incidence in post-bariatric surgery patients could reduce the effectiveness of bariatric surgery in the resolution of diabetes.}, } @article {pmid34716032, year = {2021}, author = {Pröbstel, AK and Schirmer, L}, title = {SARS-CoV-2-specific neuropathology: fact or fiction?.}, journal = {Trends in neurosciences}, volume = {44}, number = {12}, pages = {933-935}, pmid = {34716032}, issn = {1878-108X}, support = {/ERC_/European Research Council/International ; }, mesh = {*COVID-19 ; Central Nervous System ; Humans ; Inflammation ; *SARS-CoV-2 ; }, abstract = {Neurological symptoms and varying levels of central nervous system (CNS) immunopathology have been described in COVID-19. Recent reports have suggested an increased level of innate immune activation associated with CNS border areas, as well as with a compartmentalized cytokine response and a dysregulated, autoreactive cerebrospinal fluid (CSF) immune profile. However, it remains contested whether these changes reflect bystander effects of systemic inflammation or relate to CNS-specific viral infection. We summarize some of the key findings pertaining to this ongoing debate and highlight directions for future investigation.}, } @article {pmid34715312, year = {2022}, author = {Smith, MP}, title = {Estimating total morbidity burden of COVID-19: relative importance of death and disability.}, journal = {Journal of clinical epidemiology}, volume = {142}, number = {}, pages = {54-59}, pmid = {34715312}, issn = {1878-5921}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; COVID-19/*complications/economics/epidemiology ; Child ; Child, Preschool ; Cost of Illness ; Disability-Adjusted Life Years/*trends ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Patient Acuity ; Sex Characteristics ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Calculations of disease burden of COVID-19, used to allocate scarce resources, have historically considered only mortality. However, survivors often develop postinfectious 'long-COVID' similar to chronic fatigue syndrome; physical sequelae such as heart damage, or both. This paper quantifies relative contributions of acute case fatality, delayed case fatality, and disability to total morbidity per COVID-19 case.

STUDY DESIGN AND SETTING: Healthy life years lost per COVID-19 case were computed as the sum of (incidence*disability weight*duration) for death and long-COVID by sex and 10-year age category in three plausible scenarios.

RESULTS: In all models, acute mortality was only a small share of total morbidity. For lifelong moderate symptoms, healthy years lost per COVID-19 case ranged from 0.92 (male in his 30s) to 5.71 (girl under 10) and were 3.5 and 3.6 for the oldest females and males. At higher symptom severities, young people and females bore larger shares of morbidity; if survivors' later mortality increased, morbidity increased most in young people of both sexes.

CONCLUSIONS: Under most conditions most COVID-19 morbidity was in survivors. Future research should investigate incidence, risk factors, and clinical course of long-COVID to elucidate total disease burden, and decisionmakers should allocate scarce resources to minimize total morbidity.}, } @article {pmid34713356, year = {2022}, author = {Karaarslan, F and Güneri, FD and Kardeş, S}, title = {Long COVID: rheumatologic/musculoskeletal symptoms in hospitalized COVID-19 survivors at 3 and 6 months.}, journal = {Clinical rheumatology}, volume = {41}, number = {1}, pages = {289-296}, pmid = {34713356}, issn = {1434-9949}, mesh = {Arthralgia ; *COVID-19/complications ; Cohort Studies ; Fatigue ; Female ; Hospitalization ; Humans ; Musculoskeletal Diseases/*virology ; Myalgia ; Rheumatic Diseases/*virology ; SARS-CoV-2 ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To document the detailed characteristics including severity, type, and locations of rheumatic and musculoskeletal symptoms along with other COVID-19 persistent symptoms in hospitalized COVID-19 survivors at 3 and 6 months.

METHODS: In this extension cohort study, two telephone surveys at 3 and 6 months following the hospitalization were carried out. In these telephone surveys, participants were asked regarding their symptoms through a previously designed standard questionnaire.

RESULTS: At 3 months, 89.0% of survivors had at least one symptom, 74.6% had at least one rheumatic and musculoskeletal symptom, and 82.1% had at least one other COVID-19 symptom. At 6 months, 59.6% of survivors had at least one symptom, 43.2% had at least one rheumatic and musculoskeletal symptom, and 51.2% had at least one other COVID-19 symptom. Regarding the rheumatic and musculoskeletal symptoms, 31.6% had fatigue, 18.6% had joint pain, and 15.1% had myalgia; and regarding the other-COVID-19-symptoms, 25.3% had dyspnea, 20.0% had hair loss, and 17.2% sweat at 6 months. In an adjusted model, female patients were more likely to have fatigue (OR: 1.99, 95% CI: 1.18-3.34), myalgia (3.00, 1.51-5.98), and joint pain (3.39, 1.78-6.50) at 6 months.

CONCLUSION: Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom. Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms. Joint pain and myalgia were mostly widespread. This information guide rheumatologists to understand the nature and features of persistent rheumatic and musculoskeletal symptoms in hospitalized COVID-19 survivors and may contribute to better management of these individuals. Key Points • Approximately 3 in 5 patients had at least one symptom with ≈2 in 5 patients had at least one rheumatic and musculoskeletal symptom at 6 months • Fatigue, joint pain, and myalgia were the most frequent rheumatic and musculoskeletal symptoms followed by back pain, low back pain, and neck pain • Dyspnea, hair loss, and sweat were the most frequent other-COVID-19-symptoms.}, } @article {pmid34711574, year = {2021}, author = {, }, title = {Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {495}, pmid = {34711574}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Clinical Coding ; Humans ; Primary Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34711562, year = {2021}, author = {Madan, I and Briggs, T and Chew-Graham, C}, title = {Supporting patients with long COVID return to work.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {508-509}, pmid = {34711562}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; Return to Work ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34711561, year = {2021}, author = {Singh, C}, title = {Long COVID: playing the long game.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {507}, doi = {10.3399/bjgp21X717521}, pmid = {34711561}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; *Video Games ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34711556, year = {2021}, author = {Marshall-Andon, T and Walsh, S and Fuld, J and Pari, AAA}, title = {The health system response to long COVID in England - at a critical juncture.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {485-486}, pmid = {34711556}, issn = {1478-5242}, mesh = {*COVID-19/complications ; England ; Government Programs ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34711555, year = {2021}, author = {Misselbrook, D}, title = {To Long COVID and Beyond!.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {483}, pmid = {34711555}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; *Telemedicine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34710173, year = {2021}, author = {Poudel, AN and Zhu, S and Cooper, N and Roderick, P and Alwan, N and Tarrant, C and Ziauddeen, N and Yao, GL}, title = {Impact of Covid-19 on health-related quality of life of patients: A structured review.}, journal = {PloS one}, volume = {16}, number = {10}, pages = {e0259164}, pmid = {34710173}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/complications/*psychology ; Female ; Humans ; Male ; Middle Aged ; Pandemics/prevention & control ; Quality of Life/*psychology ; SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Coronavirus disease (Covid-19) has led to a global pandemic since its emergence in December 2019. The majority of research into Covid-19 has focused on transmission, and mortality and morbidity associated with the virus. However, less attention has been given to its impact on health-related quality of life (HRQoL) of patients with Covid-19.

METHODS: We searched for original studies published between December 2019 and Jan 2021 in PubMed, Scopus and Medline databases using a specific search strategy. We also explored literature on websites of distinguished public health organisations and hand-searched reference lists of eligible studies. The studies were screened by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart using pre-determined eligibility criteria. Data were synthesised, analysed descriptively and reported in line with PRISMA guidelines.

RESULTS: In total, 1276 studies were identified through the search strategy. Of these, 77 studies were selected for full-text reading after screening the studies. After reading full-text, 12 eligible studies were included in this review. The majority of the studies used a generic HRQoL assessment tool; five studies used SF-36, five studies used EQ-5D-5L, and three used pulmonary disease-specific HRQoL tools (two studies used two tools each). The impact of Covid-19 on HRQoL was found to be considerable in both Acute Covid and Long Covid patients. Higher impact on HRQoL was reported in Acute Covid, females, older ages, patients with more severe disease and patients from low-income countries.

CONCLUSION: The impact of Covid-19 on HRQoL of Acute and Long Covid patients is substantial. There was disproportional impact on patients by gender, age, severity of illness and study country. The long-term impact of Covid-19 is still in its initial stage. The findings of the review may be useful to researchers, policymakers, and clinicians caring for people following Covid-19 infection.}, } @article {pmid34709019, year = {2022}, author = {Rasulo, FA and Piva, S and Latronico, N}, title = {Long-term complications of COVID-19 in ICU survivors: what do we know?.}, journal = {Minerva anestesiologica}, volume = {88}, number = {1-2}, pages = {72-79}, doi = {10.23736/S0375-9393.21.16032-8}, pmid = {34709019}, issn = {1827-1596}, mesh = {*COVID-19/complications ; Critical Care/psychology ; Critical Illness ; Humans ; Intensive Care Units ; SARS-CoV-2 ; Survivors/psychology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) has caused more than 175 million persons infected and 3.8 million deaths so far and is having a devastating impact on both low and high-income countries, in particular on hospitals and Intensive Care Units (ICU). The ICU mortality during the first pandemic wave ranged from 40% to 85% during the busiest ICU period for admissions around the peak of the surge, and those surviving are frequently faced with impairments affecting physical, cognitive, and mental health status, complicating the postacute phase of COVID-19, which in the pre-COVID period, were defined collectively as postintensive care syndrome (PICS). Long COVID is defined as four weeks of persisting symptoms after the acute illness, and post-COVID syndrome and chronic COVID-19 are the proposed terms to describe continued symptomatology for more than 12 weeks. Overall, 50% of ICU survivors suffer from new physical, mental, and/or cognitive problems at 1 year after ICU discharge. The prevalence, severity, and duration of the various impairments in ICU survivors are poorly defined, with substantial variations among published series, and may reflect differences in the timing of assessment, the outcome measured, the instruments utilized, and thresholds adopted to establish the diagnosis, the qualification of personnel delivering the tests, the resource availability as well diversity in patients' case-mix. Future longitudinal studies of adequate sample size with repeated assessments of validated outcomes and comparison with non-COVID-19 ICU patients are needed to fully explore the long-term outcome of ICU patients with COVID-19. In this article, we focus on chronic COVID-19 in ICU survivors and present state-of-the-art data regarding long-term complications related to critical illness and the treatments and organ support received.}, } @article {pmid34707521, year = {2021}, author = {Murga, I and Aranburu, L and Gargiulo, PA and Gómez Esteban, JC and Lafuente, JV}, title = {Clinical Heterogeneity in ME/CFS. A Way to Understand Long-COVID19 Fatigue.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {735784}, pmid = {34707521}, issn = {1664-0640}, abstract = {The aim of present paper is to identify clinical phenotypes in a cohort of patients affected of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ninety-one patients and 22 healthy controls were studied with the following questionnaires, in addition to medical history: visual analogical scale for fatigue and pain, DePaul questionnaire (post-exertional malaise, immune, neuroendocrine), Pittsburgh sleep quality index, COMPASS-31 (dysautonomia), Montreal cognitive assessment, Toulouse-Piéron test (attention), Hospital Anxiety and Depression test and Karnofsky scale. Co-morbidities and drugs-intake were also recorded. A hierarchical clustering with clinical results was performed. Final study group was made up of 84 patients, mean age 44.41 ± 9.37 years (66 female/18 male) and 22 controls, mean age 45 ± 13.15 years (14 female/8 male). Patients meet diagnostic criteria of Fukuda-1994 and Carruthers-2011. Clustering analysis identify five phenotypes. Two groups without fibromyalgia were differentiated by various levels of anxiety and depression (13 and 20 patients). The other three groups present fibromyalgia plus a patient without it, but with high scores in pain scale, they were segregated by prevalence of dysautonomia (17), neuroendocrine (15), and immunological affectation (19). Regarding gender, women showed higher scores than men in cognition, pain level and depressive syndrome. Mathematical tools are a suitable approach to objectify some elusive features in order to understand the syndrome. Clustering unveils phenotypes combining fibromyalgia with varying degrees of dysautonomia, neuroendocrine or immune features and absence of fibromyalgia with high or low levels of anxiety-depression. There is no a specific phenotype for women or men.}, } @article {pmid34704256, year = {2022}, author = {Wallin, E and Hultström, M and Lipcsey, M and Frithiof, R and Rubertsson, S and Larsson, IM}, title = {Intensive care-treated COVID-19 patients' perception of their illness and remaining symptoms.}, journal = {Acta anaesthesiologica Scandinavica}, volume = {66}, number = {2}, pages = {240-247}, pmid = {34704256}, issn = {1399-6576}, support = {SLS-938101//Svenska Läkaresällskapet/ ; 2014-02569//Vetenskapsrådet/ ; 2014-07606//Vetenskapsrådet/ ; KAW 2020.0182//Knut och Alice Wallenbergs Stiftelse/ ; }, mesh = {*COVID-19 ; Critical Care ; Humans ; Perception ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The remaining symptoms in patients with coronavirus disease 2019 (COVID-19) treated in intensive care unit are limited described. Therefore, we assessed patient's perception of their COVID-19 disease, stay in intensive care, and remaining symptoms three to six months after intensive care.

METHODS: Prospective cohort study was performed in one intensive care unit of a university hospital in Sweden during the first wave. A questionnaire with open-ended questions and closed-ended questions was used. Data were analyzed using qualitative and quantitative content analysis and descriptive statistics.

RESULTS: Out of 123 patients treated for COVID-19, 64 answered the questionnaire 3-6 months after discharge from intensive care. Memories from illness and hospital stay revealed in three categories; awareness of the illness, losing anchor to reality and being cared for in a dynamic environment. Information was perceived as spare by 48% and they wanted the information to be more personal. The diary was perceived as personal and was received by 33% patients. The relationship with family was affected among 39% and 13% of the patients indicated that they had not resumed their daily life. A large amount, 84%, indicated that they had remaining symptoms from COVID-19. The dominated symptoms were impaired strength and energy both physically and mentally.

CONCLUSION: Patients reported a variety of physical and mental symptoms, and revealed memories from the ICU, and specific awareness of other patients' health. It illustrates the need for screening patients for remaining symptoms after COVID-19 disease and ICU care and may affect resuming patients' daily life.}, } @article {pmid34704045, year = {2021}, author = {Kalyanaraman, B}, title = {Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer.}, journal = {RSC chemical biology}, volume = {2}, number = {5}, pages = {1402-1414}, pmid = {34704045}, issn = {2633-0679}, abstract = {This review analyzes the published literature linking the different mechanisms focused on oxidative stress and inflammation that contribute to COVID-19 disease severity. The objective is to bring together potential proinflammatory mechanisms of COVID-19 pathogenesis and address mitigation strategies using naturally occurring compounds and FDA-approved drugs. Outstanding questions addressed include the following: What is the mechanistic basis for linking enhanced vulnerability in COVID-19 to increased oxidative damage and proinflammatory mediators (e.g., cytokines), especially in high-risk people? Can we repurpose anti-inflammatory and immunomodulatory agents to mitigate inflammation in COVID-19 patients? How does 2-deoxy-d-glucose function as an anti-COVID drug? COVID-19, cancer biology, and immunotherapy share many mechanistic similarities. Repurposing drugs that already have been FDA-approved for mitigating inflammation and immunosuppression in cancer may be a way to counteract disease severity, progression, and chronic inflammation in COVID-19. What are the long-term effects of reactive oxygen species-inducing immune cells and sustained inflammation in so-called long-haulers (long COVID) after recovery from COVID-19? Can we use mitochondria-targeted agents prophylactically to prevent inflammation and boost immunity in long-haulers? Addressing the oxidative chemical biology of COVID-19 and the mechanistic commonalities with cancer may provide new insights potentially leading to appropriate clinical trials and new treatments.}, } @article {pmid34696427, year = {2021}, author = {Carubbi, F and Alunno, A and Leone, S and Di Gregorio, N and Mancini, B and Viscido, A and Del Pinto, R and Cicogna, S and Grassi, D and Ferri, C}, title = {Pericarditis after SARS-CoV-2 Infection: Another Pebble in the Mosaic of Long COVID?.}, journal = {Viruses}, volume = {13}, number = {10}, pages = {}, pmid = {34696427}, issn = {1999-4915}, mesh = {Aged ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; COVID-19/*complications/pathology ; Colchicine/therapeutic use ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Male ; Middle Aged ; Pericardial Effusion/pathology ; Pericarditis/*drug therapy/pathology/virology ; Pericardium/pathology/virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {With the emerging success of the COVID-19 vaccination programs, the incidence of acute COVID-19 will decrease. However, given the high number of people who contracted SARS-CoV-2 infection and recovered, we will be faced with a significant number of patients with persistent symptoms even months after their COVID-19 infection. In this setting, long COVID and its cardiovascular manifestations, including pericarditis, need to become a top priority for healthcare systems as a new chronic disease process. Concerning the relationship between COVID-19 and pericardial diseases, pericarditis appears to be common in the acute infection but rare in the postacute period, while small pericardial effusions may be relatively common in the postacute period of COVID-19. Here, we reported a series of 7 patients developing pericarditis after a median of 20 days from clinical and virological recovery from SARS-CoV-2 infection. We excluded specific identifiable causes of pericarditis, hence we speculate that these cases can be contextualized within the clinical spectrum of long COVID. All our patients were treated with a combination of colchicine and either ASA or NSAIDs, but four of them did not achieve a clinical response. When switched to glucocorticoids, these four patients recovered with no recurrence during drug tapering. Based on this observation and on the latency of pericarditis occurrence (a median of 20 days after a negative nasopharyngeal swab), could be suggested that post-COVID pericarditis may be linked to ongoing inflammation sustained by the persistence of viral nucleic acid without virus replication in the pericardium. Therefore, glucocorticoids may be a suitable treatment option in patients not responding or intolerant to conventional therapy and who require to counteract the pericardial inflammatory component rather than direct an acute viral injury to the pericardial tissue.}, } @article {pmid34696334, year = {2021}, author = {Acanfora, D and Acanfora, C and Ciccone, MM and Scicchitano, P and Bortone, AS and Uguccioni, M and Casucci, G}, title = {The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.}, journal = {Viruses}, volume = {13}, number = {10}, pages = {}, pmid = {34696334}, issn = {1999-4915}, mesh = {Anticoagulants/therapeutic use ; Blood Coagulation/drug effects ; Blood Coagulation Disorders/drug therapy ; COVID-19/*complications ; Endothelial Cells ; Factor Xa Inhibitors/therapeutic use ; Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Inflammation/drug therapy ; Male ; Middle Aged ; SARS-CoV-2/pathogenicity ; Systemic Inflammatory Response Syndrome/drug therapy/immunology/*physiopathology ; Thrombosis/drug therapy/immunology/*physiopathology ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.}, } @article {pmid34696288, year = {2021}, author = {Shiri, T and Evans, M and Talarico, CA and Morgan, AR and Mussad, M and Buck, PO and McEwan, P and Strain, WD}, title = {Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across All Ages: A Population-Based Modeling Study Using the UK as an Example.}, journal = {Vaccines}, volume = {9}, number = {10}, pages = {}, pmid = {34696288}, issn = {2076-393X}, support = {N/a//Moderna Therapeutics (United States)/ ; }, abstract = {Debate persists around the risk-benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy.}, } @article {pmid34696160, year = {2021}, author = {Günl, F and Mecate-Zambrano, A and Rehländer, S and Hinse, S and Ludwig, S and Brunotte, L}, title = {Shooting at a Moving Target-Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development.}, journal = {Vaccines}, volume = {9}, number = {10}, pages = {}, pmid = {34696160}, issn = {2076-393X}, support = {BR 5189/1-1//Deutsche Forschungsgemeinschaft/ ; CRU342//Clinical Research Unit/ ; 01KI20218//Bundesministerium für Bildung und Forschung/ ; 01KX2021//Network University Medicine/ ; Bru2/015/19//Interdisciplinary Centre for Clinical Research (IZKF)/ ; }, abstract = {Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID-19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.}, } @article {pmid34694106, year = {2021}, author = {Becker, C and Beck, K and Zumbrunn, S and Memma, V and Herzog, N and Bissmann, B and Gross, S and Loretz, N and Mueller, J and Amacher, SA and Bohren, C and Schaefert, R and Bassetti, S and Fux, C and Mueller, B and Schuetz, P and Hunziker, S}, title = {Long COVID 1 year after hospitalisation for COVID-19: a prospective bicentric cohort study.}, journal = {Swiss medical weekly}, volume = {151}, number = {}, pages = {w30091}, doi = {10.4414/smw.2021.w30091}, pmid = {34694106}, issn = {1424-3997}, mesh = {Antibodies, Viral ; B-Lymphocytes ; *COVID-19 ; Humans ; Quality of Life ; SARS-CoV-2 ; Switzerland ; }, abstract = {AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae — appearing or persisting after the typical convalescence period — of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00–1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04–1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94–1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.}, } @article {pmid34694037, year = {2022}, author = {Howard-Jones, AR and Burgner, DP and Crawford, NW and Goeman, E and Gray, PE and Hsu, P and Kuek, S and McMullan, BJ and Tosif, S and Wurzel, D and Bowen, AC and Danchin, M and Koirala, A and Sharma, K and Yeoh, DK and Britton, PN}, title = {COVID-19 in children. II: Pathogenesis, disease spectrum and management.}, journal = {Journal of paediatrics and child health}, volume = {58}, number = {1}, pages = {46-53}, pmid = {34694037}, issn = {1440-1754}, mesh = {*COVID-19/complications ; Child ; Humans ; Pandemics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global disruption of the COVID-19 pandemic has impacted the life of every child either directly or indirectly. This review explores the pathophysiology, immune response, clinical presentation and treatment of COVID-19 in children, summarising the most up-to-date data including recent developments regarding variants of concern. The acute infection with SARS-CoV-2 is generally mild in children, whilst the post-infectious manifestations, including paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and 'long COVID' in children, are more complex. Given that most research on COVID-19 has focused on adult cohorts and that clinical manifestations, treatment availability and impacts differ markedly in children, research that specifically examines COVID-19 in children needs to be prioritised.}, } @article {pmid34693230, year = {2021}, author = {Cassar, MP and Tunnicliffe, EM and Petousi, N and Lewandowski, AJ and Xie, C and Mahmod, M and Samat, AHA and Evans, RA and Brightling, CE and Ho, LP and Piechnik, SK and Talbot, NP and Holdsworth, D and Ferreira, VM and Neubauer, S and Raman, B}, title = {Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19.}, journal = {EClinicalMedicine}, volume = {41}, number = {}, pages = {101159}, pmid = {34693230}, issn = {2589-5370}, support = {FS/18/3/33292/BHF_/British Heart Foundation/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19.

METHODS: Fifty-eight patients and thirty matched controls (single visit), recruited between 14[th] March - 25[th] May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months.

FINDINGS: At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m[2], P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures.

INTERPRETATION: In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.

FUNDING: The authors' work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107.}, } @article {pmid34692410, year = {2021}, author = {Birch, S and Alraek, T and Gröbe, S}, title = {Reflections on the potential role of acupuncture and Chinese herbal medicine in the treatment of Covid-19 and subsequent health problems.}, journal = {Integrative medicine research}, volume = {10}, number = {Suppl}, pages = {100780}, pmid = {34692410}, issn = {2213-4220}, } @article {pmid34690357, year = {2022}, author = {Martín-Garrido, I and Medrano-Ortega, FJ}, title = {[Beyond acute SARS-CoV-2 infection: A new challenge for Internal Medicine].}, journal = {Revista clinica espanola}, volume = {222}, number = {3}, pages = {176-179}, pmid = {34690357}, issn = {1578-1860}, abstract = {Infection with the new SARS-CoV-2 coronavirus has reached pandemic proportions, with a very high death toll worldwide. Despite the scientific community's strenuous efforts to address this disease in its acute phase, as well as in prevention through the development of vaccines in record time, there remains another important workhorse: understanding and treating the persistence of symptoms beyond the acute phase, the so-called protracted COVID-19 syndrome or persistent COVID. These persistent manifestations affect several organs and systems and may depend on both the pathogenic mechanisms of the virus and the pathophysiological response of the patient. One year after the onset of this pandemic, there is an urgent need to address this situation from a comprehensive approach.}, } @article {pmid34689061, year = {2021}, author = {Bouteleux, B and Henrot, P and Ernst, R and Grassion, L and Raherison-Semjen, C and Beaufils, F and Zysman, M and Delorme, M}, title = {Respiratory rehabilitation for Covid-19 related persistent dyspnoea: A one-year experience.}, journal = {Respiratory medicine}, volume = {189}, number = {}, pages = {106648}, pmid = {34689061}, issn = {1532-3064}, mesh = {Adult ; Age Factors ; Aged ; COVID-19/*complications ; Dyspnea/epidemiology/*etiology/*rehabilitation ; Female ; Follow-Up Studies ; Humans ; Hyperventilation/epidemiology/*etiology/*rehabilitation ; Longitudinal Studies ; Male ; Middle Aged ; Outpatients ; Prevalence ; Quality of Life ; Referral and Consultation ; Rehabilitation/*methods ; *Respiration ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Growing consideration is emerging regarding the burden of persisting sequelae after SARS-CoV-2 infection. Out-patients exhibiting long Covid may benefit from ambulatory rehabilitation which is, to date, poorly documented.

METHODS: A longitudinal follow-up over a one-year period was conducted in two ambulatory rehabilitation structures in order to describe the characteristics of real-life patients referred with Covid-19 sequelae and their evolution over the course of rehabilitation.

RESULTS: 39 consecutive patients were included from April 1st[,] 2020 to April 1st[,] 2021. Patients were middle-aged (48 ± 15yr), without comorbidities, and mostly mild to moderate SARS-CoV-2 infection (25(64%) not requiring hospitalisation). Rehabilitation referral was considered with a median delay of 73[34-178] days after disease onset. Most prevalent symptoms were dyspnoea (n = 35(90%)) and fatigue (n = 30(77%)). Hyperventilation syndrome was highly frequent (n = 12(34%)). 29(74%) patients presented with prolonged functional sequelae, which was associated with younger age (43 ± 14 vs. 50 ± 10yr; p = 0.002), greater prevalence of hyperventilation syndrome (n = 12(41%) vs. 0(0%); p = 0.255) and poorer quality of life (VQ-11; 31 ± 10 vs. 23 ± 9; p = 0.030). Over the course of rehabilitation, exertional dyspnoea, 6-min walking distance, 3-min sit-to-stand test, hyperventilation syndrome prevalence and quality of life significantly improved.

CONCLUSION: Hyperventilation is frequent in long Covid and may explain persistent dyspnoea as well as altered quality of life. Our data support screening of hyperventilation syndrome and functional impairment in mild Covid-19 out-patients as both of these components may improve with ambulatory rehabilitation.}, } @article {pmid34688543, year = {2022}, author = {Kopanczyk, R and Kumar, N and Papadimos, T}, title = {Post-Acute COVID-19 Syndrome for Anesthesiologists: A Narrative Review and a Pragmatic Approach to Clinical Care.}, journal = {Journal of cardiothoracic and vascular anesthesia}, volume = {36}, number = {8 Pt A}, pages = {2727-2737}, pmid = {34688543}, issn = {1532-8422}, mesh = {Anesthesiologists ; *COVID-19/complications ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute coronavirus disease 2019 (COVID-19) syndrome is a novel, poorly understood clinical entity with life-impacting ramifications. Patients with this syndrome, also known as "COVID-19 long-haulers," often present with nonspecific ailments involving more than one body system. The most common complaints include dyspnea, fatigue, brain fog, and chest pain. There currently is no single agreed-upon definition for post-acute COVID-19 syndrome, but most agree that criterion for this syndrome is the persistence of mental and physical health consequences after initial infection. Given the millions of acute infections in the United States over the course of the pandemic, perioperative providers will encounter these patients in clinical practice in growing numbers. Symptoms of the COVID-19 long-haulers should not be minimized, as these patients are at higher risk for postoperative respiratory complications and perioperative mortality for up to seven weeks after initial illness. Instead, a cautious multidisciplinary preoperative evaluation should be performed. Perioperative care should be viewed through the prism of best practices already in use, such as avoidance of benzodiazepines in patients with cognitive impairment and use of lung-protective ventilation. Recommendations especially relevant to the COVID-19 long-haulers include assessment of critical care myopathies and neuropathies to determine suitable neuromuscular blocking agents and reversal, preoperative workup of insidious cardiac or pulmonary pathologies in previously healthy patients, and, thorough medication review, particularly of anticoagulation regimens and chronic steroid use. In this article, the authors define the syndrome, synthesize the available scientific evidence, and make pragmatic suggestions regarding the perioperative clinical care of COVID-19 long-haulers.}, } @article {pmid34688435, year = {2021}, author = {Altmann, DM and Boyton, RJ}, title = {Waning immunity to SARS-CoV-2: implications for vaccine booster strategies.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {12}, pages = {1356-1358}, pmid = {34688435}, issn = {2213-2619}, support = {MR/R02622X/1/MRC_/Medical Research Council/United Kingdom ; MR/S019553/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; Vaccination ; *Vaccines ; }, } @article {pmid34687462, year = {2022}, author = {Korompoki, E and Gavriatopoulou, M and Fotiou, D and Ntanasis-Stathopoulos, I and Dimopoulos, MA and Terpos, E}, title = {Late-onset hematological complications post COVID-19: An emerging medical problem for the hematologist.}, journal = {American journal of hematology}, volume = {97}, number = {1}, pages = {119-128}, pmid = {34687462}, issn = {1096-8652}, mesh = {Animals ; COVID-19/*complications/etiology/therapy ; Disease Management ; Hematologic Diseases/*etiology/therapy ; Hemorrhagic Disorders/etiology/therapy ; Humans ; SARS-CoV-2/isolation & purification ; Thrombocytopenia/etiology/therapy ; Thromboembolism/etiology/therapy ; Thrombosis/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 19 (COVID-19) is considered a multisystemic disease. Several studies have reported persistent symptoms or late-onset complications after acute COVID-19, including post-COVID-19 hematological disorders. COVID-19-induced coagulopathy, an immunothrombotic state, has been linked to thromboembolic and hemorrhagic events. Late-onset thrombocytopenia related to immune system dysregulation has also been reported as a rare manifestation post COVID-19. Close monitoring of laboratory dynamics is considered essential to identify timely abnormal values that need further investigation, providing supportive care whenever indicated. The role of hematologists is essential in terms of the multidisciplinary approach of long COVID-19. This review summarizes all the available evidence on post-acute COVID-19 hematological complications.}, } @article {pmid34687321, year = {2022}, author = {Trapani, V and Rosanoff, A and Baniasadi, S and Barbagallo, M and Castiglioni, S and Guerrero-Romero, F and Iotti, S and Mazur, A and Micke, O and Pourdowlat, G and Scarpati, G and Wolf, FI and Maier, JA}, title = {The relevance of magnesium homeostasis in COVID-19.}, journal = {European journal of nutrition}, volume = {61}, number = {2}, pages = {625-636}, pmid = {34687321}, issn = {1436-6215}, mesh = {*COVID-19 ; Homeostasis ; Humans ; Magnesium ; Pandemics ; SARS-CoV-2 ; }, abstract = {PURPOSE: In less than one and a half year, the COVID-19 pandemic has nearly brought to a collapse our health care and economic systems. The scientific research community has concentrated all possible efforts to understand the pathogenesis of this complex disease, and several groups have recently emphasized recommendations for nutritional support in COVID-19 patients. In this scoping review, we aim at encouraging a deeper appreciation of magnesium in clinical nutrition, in view of the vital role of magnesium and the numerous links between the pathophysiology of SARS-CoV-2 infection and magnesium-dependent functions.

METHODS: By searching PubMed and Google Scholar from 1990 to date, we review existing evidence from experimental and clinical studies on the role of magnesium in chronic non-communicable diseases and infectious diseases, and we focus on recent reports of alterations of magnesium homeostasis in COVID-19 patients and their association with disease outcomes. Importantly, we conduct a census on ongoing clinical trials specifically dedicated to disclosing the role of magnesium in COVID-19.

RESULTS: Despite many methodological limitations, existing data seem to corroborate an association between deranged magnesium homeostasis and COVID-19, and call for further and better studies to explore the prophylactic or therapeutic potential of magnesium supplementation.

CONCLUSION: We propose to reconsider the relevance of magnesium, frequently overlooked in clinical practice. Therefore, magnesemia should be monitored and, in case of imbalanced magnesium homeostasis, an appropriate nutritional regimen or supplementation might contribute to protect against SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase.}, } @article {pmid34684216, year = {2021}, author = {Desforges, M and Gurdasani, D and Hamdy, A and Leonardi, AJ}, title = {Uncertainty around the Long-Term Implications of COVID-19.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {10}, pages = {}, pmid = {34684216}, issn = {2076-0817}, support = {MR/S003711/1/MRC_/Medical Research Council/United Kingdom ; MR/S003711/2/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 231 million people globally, with more than 4.7 million deaths recorded by the World Health Organization as of 26 September 2021. In response to the pandemic, some countries (New Zealand, Vietnam, Taiwan, South Korea and others) have pursued suppression strategies, so-called Zero COVID policies, to drive and maintain infection rates as close to zero as possible and respond aggressively to new cases. In comparison, European countries and North America have adopted mitigation strategies (of varying intensity and effectiveness) that aim primarily to prevent health systems from being overwhelmed. With recent advances in our understanding of SARS-CoV-2 and its biology, and the increasing recognition there is more to COVID-19 beyond the acute infection, we offer a perspective on some of the long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).}, } @article {pmid34684195, year = {2021}, author = {Kozak, R and Armstrong, SM and Salvant, E and Ritzker, C and Feld, J and Biondi, MJ and Tsui, H}, title = {Recognition of Long-COVID-19 Patients in a Canadian Tertiary Hospital Setting: A Retrospective Analysis of Their Clinical and Laboratory Characteristics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {10}, pages = {}, pmid = {34684195}, issn = {2076-0817}, support = {N/A//Sunnybrook Foundation & Sunnybrook Research Institute COVID-19 Research Initiative./ ; }, abstract = {A proportion of patients with COVID-19 have symptoms past the acute disease phase, which may affect quality of life. It is important for clinicians to be aware of this "long-COVID-19" syndrome to better diagnose, treat, and prevent it. We reviewed clinical and laboratory characteristics of a COVID-19 cohort in a Toronto, Ontario tertiary care center. Demographic, clinical, and laboratory data were collected, and patients were classified as "long-COVID-19" or "non-long-COVID-19" using consensus criteria. Of 397 patients who tested positive for COVID-19, 223 met inclusion criteria, and 62 (27%) had long-COVID-19. These patients had a similar age distribution compared to non-long-COVID-19 patients overall but were younger in the admitted long COVID-19 group. The long-COVID-19 group had more inpatients compared to the non-long-COVID-19 group (39% vs. 25%) and more frequent supplemental oxygen or mechanical ventilation use. However, long-COVID-19 patients did not differ by duration of mechanical ventilation, length of stay, comorbidities, or values of common laboratory tests ordered. The most frequent symptoms associated with long-COVID-19 were fatigue and weakness, as reported most commonly by the infectious disease, respirology and cardiology disciplines. In conclusion, by retrospective chart review, 27% of COVID-19 patients presenting to a tertiary care center in Toronto, Canada, were found to meet criteria for long-COVID-19. Past medical history and routine laboratory testing at presentation did not predict for long-COVID-19 development.}, } @article {pmid34684123, year = {2021}, author = {Salzano, C and Saracino, G and Cardillo, G}, title = {Possible Adrenal Involvement in Long COVID Syndrome.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {10}, pages = {}, pmid = {34684123}, issn = {1648-9144}, mesh = {Adrenal Glands ; *COVID-19/complications ; Dehydroepiandrosterone Sulfate ; Humans ; Hydrocortisone/therapeutic use ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. The most frequent symptoms are fatigue and cognitive dysfunction. We describe a patient suffering from Long COVID in whom adrenal involvement was highlighted. Methods: The patient described Long COVID symptoms that persist 3 months after the negativization of the molecular swab test. The main symptoms were weakness, brain fog, dizziness, and muscular and joint pain. All routine lab panels for inflammation, anemia, and thyroid and liver function were conducted. Moreover, salivary cortisol and DHEA-S determinations were used to compute the adrenal stress index (ASI). Results: All tests were negative, except the ASI that showed very low levels of free cortisol. The patient started hydrocortisone acetate supplementation. Conclusion: Long COVID symptoms could be explained by an adrenal involvement, due to a COVID-19 action on adrenal glands and by a iatrogenic side effect of high glucocorticoid therapy during the COVID-19 infection. Salivary cortisol determination is effective for establishing a correct recovery plan.}, } @article {pmid34682970, year = {2021}, author = {Chang, CJ and Hung, LY and Kogelnik, AM and Kaufman, D and Aiyar, RS and Chu, AM and Wilhelmy, J and Li, P and Tannenbaum, L and Xiao, W and Davis, RW}, title = {A Comprehensive Examination of Severely Ill ME/CFS Patients.}, journal = {Healthcare (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {34682970}, issn = {2227-9032}, abstract = {One in four myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients are estimated to be severely affected by the disease, and these house-bound or bedbound patients are currently understudied. Here, we report a comprehensive examination of the symptoms and clinical laboratory tests of a cohort of severely ill patients and healthy controls. The greatly reduced quality of life of the patients was negatively correlated with clinical depression. The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%). Sleep profiles and cognitive tests revealed distinctive impairments. Lower morning cortisol level and alterations in its diurnal rhythm were observed in the patients, and antibody and antigen measurements showed no evidence for acute infections by common viral or bacterial pathogens. These results highlight the urgent need of developing molecular diagnostic tests for ME/CFS. In addition, there was a striking similarity in symptoms between long COVID and ME/CFS, suggesting that studies on the mechanism and treatment of ME/CFS may help prevent and treat long COVID and vice versa.}, } @article {pmid34682648, year = {2021}, author = {Abu-Hammad, O and Alnazzawi, A and Babkair, H and Jambi, S and Mirah, M and Abdouh, I and Aljohani, RS and Ayeq, R and Ghazi, L and Al-Subhi, H and Dar-Odeh, N}, title = {COVID-19 Infection in Academic Dental Hospital Personnel; A Cross-Sectional Survey in Saudi Arabia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {20}, pages = {}, pmid = {34682648}, issn = {1660-4601}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Hospitals ; Humans ; Personnel, Hospital ; SARS-CoV-2 ; Saudi Arabia/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Close patient contact is an essential component of clinical dental education, which can expose students and faculty to risk of COVID-19 and its sequelae.

METHODS: The study was a cross-sectional survey conducted among faculty and clinical students at an academic dental hospital in Al Madinah western Saudi Arabia. An online questionnaire was distributed to collect data on prevalence, risk factors, clinical manifestations, and long-term health and socioeconomic complications of COVID-19 infection.

RESULTS: Prevalence of COVID-19 was 19.6% among a total of 316 students and faculty. Participants cited family and friends as the primary source of infection (40.3%). Among cross-infection control practices, they cited failure to practice distancing as the primary reason for infection transmission (61.3%). The disease was symptomatic in 85.5% of infected personnel. Most frequently reported clinical manifestations were: fever, cough, malaise, and diarrhoea (74.1%, 56.5%, 40.3%, 32.3%, respectively). A proportion of 37.1% of infected personnel stated that they had long COVID-19, and 58.3% of infected students reported deteriorated academic achievement.

CONCLUSIONS: One in five of clinical dental students and their faculty had COVID-19. Most cases were symptomatic, and a large proportion developed long COVID or adverse socioeconomic consequences. Regardless of the severity of symptoms encountered during the acute stage of COVID-19 infection, all infected dental healthcare personnel should be followed, especially those who report long COVID. Continuous follow-up and assistance for infected students may be warranted to mitigate the potential academic and mental drawbacks caused by the pandemic. Dental schools should adopt clear policies regarding COVID-19 transmission and prevention and should implement them in their infection-control education and training.}, } @article {pmid34680460, year = {2021}, author = {Mangge, H and Kneihsl, M and Schnedl, W and Sendlhofer, G and Curcio, F and Domenis, R}, title = {Immune Responses against SARS-CoV-2-Questions and Experiences.}, journal = {Biomedicines}, volume = {9}, number = {10}, pages = {}, pmid = {34680460}, issn = {2227-9059}, abstract = {Understanding immune reactivity against SARS-CoV-2 is essential for coping with the COVID-19 pandemic. Herein, we discuss experiences and open questions about the complex immune responses to SARS-CoV-2. Some people react excellently without experiencing any clinical symptoms, they do not get sick, and they do not pass the virus on to anyone else ("sterilizing" immunity). Others produce antibodies and do not get COVID-19 but transmit the virus to others ("protective" immunity). Some people get sick but recover. A varying percentage develops respiratory failure, systemic symptoms, clotting disorders, cytokine storms, or multi-organ failure; they subsequently decease. Some develop long COVID, a new pathologic entity similar to fatigue syndrome or autoimmunity. In reality, COVID-19 is considered more of a systemic immune-vascular disease than a pulmonic disease, involving many tissues and the central nervous system. To fully comprehend the complex clinical manifestations, a profound understanding of the immune responses to SARS-CoV-2 is a good way to improve clinical management of COVID-19. Although neutralizing antibodies are an established approach to recognize an immune status, cellular immunity plays at least an equivalent or an even more important role. However, reliable methods to estimate the SARS-CoV-2-specific T cell capacity are not available for clinical routines. This deficit is important because an unknown percentage of people may exist with good memory T cell responsibility but a low number of or completely lacking peripheral antibodies against SARS-CoV-2. Apart from natural immune responses, vaccination against SARS-CoV-2 turned out to be very effective and much safer than naturally acquired immunity. Nevertheless, besides unwanted side effects of the currently available vector and mRNA preparations, concerns remain whether these vaccines will be strong enough to defeat the pandemic. Altogether, herein we discuss important questions, and try to give answers based on the current knowledge and preliminary data from our laboratories.}, } @article {pmid34678422, year = {2022}, author = {Inciardi, RM and Chandra, A}, title = {Editorial commentary: Long COVID-19: A tangled web of lungs, heart, mind, and gender.}, journal = {Trends in cardiovascular medicine}, volume = {32}, number = {1}, pages = {18-19}, pmid = {34678422}, issn = {1873-2615}, mesh = {*COVID-19/complications ; Heart ; Humans ; Lung ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34678309, year = {2022}, author = {Reddy, R and Efimenko, I and Chertman, W and Kohn, T and Diaz, P and Seetharam, D and Khodamoradi, K and Kresch, E and Ramasamy, R}, title = {Whole Exome Sequencing Identifies a Rare Mutation in NACAD as a Possible Cause of COVID Orchitis in Brothers.}, journal = {Urology}, volume = {159}, number = {}, pages = {83-86}, pmid = {34678309}, issn = {1527-9995}, mesh = {Adult ; Angiotensin-Converting Enzyme 2/blood ; COVID-19/*complications ; *Chromosome Deletion ; *Chromosomes, Human, Pair 7 ; Frameshift Mutation ; Humans ; Male ; Orchitis/*virology ; Siblings ; *Exome Sequencing ; }, abstract = {COVID orchitis (testicular pain) is reported in 10-15% of men with long COVID. We identified 2 siblings with COVID orchitis and hypothesized that genetic mutations are associated with susceptibility. Blood samples from 5 COVID-19 (+) men, three of whom had orchitis were evaluated by whole-exome-sequencing. A rare deletion on chromosome 7 was found in NACAD among the 3 men with orchitis. Interestingly, circulating ACE2 levels was decreased in men with COVID orchitis. This pilot study generated the hypothesis that men who develop COVID orchitis could have underlying genetic variants and altered levels in circulating ACE2 that may increase their risk.}, } @article {pmid34677601, year = {2021}, author = {Peluso, MJ and Lu, S and Tang, AF and Durstenfeld, MS and Ho, HE and Goldberg, SA and Forman, CA and Munter, SE and Hoh, R and Tai, V and Chenna, A and Yee, BC and Winslow, JW and Petropoulos, CJ and Greenhouse, B and Hunt, PW and Hsue, PY and Martin, JN and Daniel Kelly, J and Glidden, DV and Deeks, SG and Henrich, TJ}, title = {Markers of Immune Activation and Inflammation in Individuals With Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.}, journal = {The Journal of infectious diseases}, volume = {224}, number = {11}, pages = {1839-1848}, pmid = {34677601}, issn = {1537-6613}, support = {K24 AI145806/AI/NIAID NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; K12 HL143961/HL/NHLBI NIH HHS/United States ; K24 AI112393/AI/NIAID NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; K23 AI076614/AI/NIAID NIH HHS/United States ; 3R01AI141003-03S1/NH/NIH HHS/United States ; }, mesh = {Biomarkers/blood ; *COVID-19/complications/immunology ; Cytokines/blood ; Disease Progression ; Humans ; *Inflammation/blood/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown.

METHODS: We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods.

RESULTS: During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P < .001). These differences were more pronounced among those with a greater number of PASC symptoms.

CONCLUSIONS: Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.}, } @article {pmid34677202, year = {2021}, author = {Marazzato, J and De Ponti, R and Verdecchia, P and Masnaghetti, S and Visca, D and Spanevello, A and Trapasso, M and Zappa, M and Mancinelli, A and Angeli, F}, title = {Combined Use of Electrocardiography and Ultrasound to Detect Cardiac and Pulmonary Involvement after Recovery from COVID-19 Pneumonia: A Case Series.}, journal = {Journal of cardiovascular development and disease}, volume = {8}, number = {10}, pages = {}, pmid = {34677202}, issn = {2308-3425}, abstract = {BACKGROUND: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia.

METHODS: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT).

RESULTS: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients.

CONCLUSIONS: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.}, } @article {pmid34676578, year = {2022}, author = {O'Connor, RJ and Preston, N and Parkin, A and Makower, S and Ross, D and Gee, J and Halpin, SJ and Horton, M and Sivan, M}, title = {The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS): Application and psychometric analysis in a post-COVID-19 syndrome cohort.}, journal = {Journal of medical virology}, volume = {94}, number = {3}, pages = {1027-1034}, pmid = {34676578}, issn = {1096-9071}, support = {MC_PC_19042/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Humans ; Prospective Studies ; Psychometrics/methods ; Reproducibility of Results ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {As our understanding of the nature and prevalence of post-coronavirus disease 2019 (COVID-19) syndrome (PCS) is increasing, a measure of the impact of COVID-19 could provide valuable insights into patients' perceptions in clinical trials and epidemiological studies as well as routine clinical practice. To evaluate the clinical usefulness and psychometric properties of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) in patients with PCS, a prospective, observational study of 187 consecutive patients attending a post-COVID-19 rehabilitation clinic was conducted. The C19-YRS was used to record patients' symptoms, functioning, and disability. A global health question was used to measure the overall impact of PCS on health. Classical psychometric methods (data quality, scaling assumptions, targeting, reliability, and validity) were used to assess the C19-YRS. For the total group, missing data were low, scaling and targeting assumptions were satisfied, and internal consistency was high (Cronbach's α = 0.891). Relationships between the overall perception of health and patients' reports of symptoms, functioning, and disability demonstrated good concordance. This is the first study to examine the psychometric properties of an outcome measure in patients with PCS. In this sample of patients, the C19-YRS was clinically useful and satisfied standard psychometric criteria, providing preliminary evidence of its suitability as a measure of PCS.}, } @article {pmid34674007, year = {2021}, author = {Williams, S and Wynford-Thomas, R and Robertson, NP}, title = {Long-COVID: neurological manifestations and management.}, journal = {Journal of neurology}, volume = {268}, number = {12}, pages = {4915-4917}, doi = {10.1007/s00415-021-10847-5}, pmid = {34674007}, issn = {1432-1459}, mesh = {*COVID-19/complications ; Humans ; *Nervous System Diseases/etiology/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34674005, year = {2022}, author = {Beghi, E and Giussani, G and Westenberg, E and Allegri, R and Garcia-Azorin, D and Guekht, A and Frontera, J and Kivipelto, M and Mangialasche, F and Mukaetova-Ladinska, EB and Prasad, K and Chowdhary, N and Winkler, AS}, title = {Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.}, journal = {Journal of neurology}, volume = {269}, number = {5}, pages = {2265-2274}, pmid = {34674005}, issn = {1432-1459}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*COVID-19/complications ; Hospital Mortality ; Humans ; *Nervous System Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified.}, } @article {pmid34673642, year = {2022}, author = {Aiello, M and Marchi, L and Calzetta, L and Speroni, S and Frizzelli, A and Ghirardini, M and Celiberti, V and Sverzellati, N and Majori, M and Mori, PA and Ranzieri, S and Pisi, R and Pelà, G and Corradi, M and Chetta, A}, title = {Coronavirus Disease 2019: COSeSco - A Risk Assessment Score to Predict the Risk of Pulmonary Sequelae in COVID-19 Patients.}, journal = {Respiration; international review of thoracic diseases}, volume = {101}, number = {3}, pages = {272-280}, pmid = {34673642}, issn = {1423-0356}, mesh = {*COVID-19/complications ; Humans ; Lung/diagnostic imaging/physiopathology ; Respiratory Function Tests/methods ; Risk Assessment ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae.

OBJECTIVES: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors.

METHODS: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT.

RESULTS: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity <80% of predicted). Age, BMI, CCI, D-dimer, 6MWT, and mMRC were included in the COVID-19 Sequelae Score (COSeSco, ranging 0-15), which was able to individuate COVID-19 patients with radiologic sequelae (HRCT score >10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2.

CONCLUSION: The COSeSco - comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception - makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.}, } @article {pmid34672377, year = {2022}, author = {Asadi-Pooya, AA and Akbari, A and Emami, A and Lotfi, M and Rostamihosseinkhani, M and Nemati, H and Barzegar, Z and Kabiri, M and Zeraatpisheh, Z and Farjoud-Kouhanjani, M and Jafari, A and Sasannia, S and Ashrafi, S and Nazeri, M and Nasiri, S and Shahisavandi, M}, title = {Long COVID syndrome-associated brain fog.}, journal = {Journal of medical virology}, volume = {94}, number = {3}, pages = {979-984}, pmid = {34672377}, issn = {1096-9071}, mesh = {Adult ; Brain ; *COVID-19/complications ; COVID-19 Testing ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease-2019 (COVID-19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18-55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post-COVID "brain fog" by the patients. In this large population-based study, we report that chronic post-COVID "brain fog" has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).}, } @article {pmid34670282, year = {2021}, author = {Gogoll, C and Leo, F and Schueller, PO and Grohé, C}, title = {[Post-COVID sequela of the lung - follow up and treatment].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {21}, pages = {1399-1404}, doi = {10.1055/a-1492-8808}, pmid = {34670282}, issn = {1439-4413}, mesh = {COVID-19/*complications/epidemiology/physiopathology/therapy ; Europe ; Humans ; Incidence ; Practice Guidelines as Topic ; Post-Acute COVID-19 Syndrome ; }, abstract = {Most people recover completely after an acute infection with the novel corona virus SARS-CoV2. But some people continue to experience symptoms after their recovery. This phenomenon is called post-acute or long-COVID (from week 4 after the infection up to week 12) and persistent post-COVID (symptoms for effects that persist 12 or more weeks after onset). The exact processes that cause long COVID remain unknown.Most of those patients suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise. Today, 18 months after the first infections in Europe we have access to the first practical guidelines for the long-/post-COVID syndrome. Further on first prospective studies analysing the incidence of post-COVID are now available.In this review we will discuss some questions about treatment and follow up of patients suffering from pulmonary sequelae after their COVID-19 infection, based on the actual literature.}, } @article {pmid34667307, year = {2021}, author = {Boyton, RJ and Altmann, DM}, title = {The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?.}, journal = {Nature reviews. Immunology}, volume = {21}, number = {12}, pages = {762-768}, pmid = {34667307}, issn = {1474-1741}, support = {MC_PC_20031/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; MR/S019553/1/MRC_/Medical Research Council/United Kingdom ; MR/R02622X/1/MRC_/Medical Research Council/United Kingdom ; MR/W020610/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Asymptomatic Infections/epidemiology ; COVID-19/complications/epidemiology/*immunology/*transmission ; Humans ; *Immunologic Memory ; SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection.}, } @article {pmid34665645, year = {2022}, author = {Muller, AE and Berg, RC and Jardim, PSJ and Johansen, TB and Ormstad, SS}, title = {Can Remote Patient Monitoring Be the New Standard in Primary Care of Chronic Diseases, Post-COVID-19?.}, journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association}, volume = {28}, number = {7}, pages = {942-969}, doi = {10.1089/tmj.2021.0399}, pmid = {34665645}, issn = {1556-3669}, mesh = {Adult ; *COVID-19/epidemiology ; Chronic Disease ; *Diabetes Mellitus/therapy ; Humans ; *Hypertension/therapy ; Monitoring, Physiologic/methods ; Pandemics ; Primary Health Care ; Quality of Life ; }, abstract = {Background: One lesson from the current COVID-19 pandemic is the need to optimize health care provision outside of traditional settings, and potentially over longer periods of time. An important strategy is remote patient monitoring (RPM), allowing patients to remain at home, while they transmit health data and receive follow-up services. Materials and Methods: We conducted an overview of the latest systematic reviews that had included randomized controlled trials with adult patients with chronic diseases. We summarized results and displayed these in forest plots, and used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) to assess our certainty of the evidence. Results: We included 4 systematic reviews that together reported on 11 trials that met our definition of RPM, each including patients with diabetes and/or hypertension. RPM probably makes little to no difference on HbA1c levels. RPM probably leads to a slight reduction in systolic blood pressure, with questionable clinical meaningfulness. RPM probably has a small negative effect on the physical component of health-related quality of life, but the clinical significance of this reduction is uncertain. We have low confidence in the finding that RPM makes no difference to the remaining five primary outcomes. Conclusion: Most of our findings are consistent with reviews of other, broader definitions of RPM. The type of RPM examined in this review is as effective as standard treatment for patients with diabetes/hypertension. If this or other types of RPM are to be used for "long covid" patients or for other chronic disease groups post-pandemic, we need to understand why RPM may negatively affect quality of life.}, } @article {pmid34659752, year = {2021}, author = {Viszlayová, D and Sojka, M and Dobrodenková, S and Szabó, S and Bilec, O and Turzová, M and Ďurina, J and Baloghová, B and Borbély, Z and Kršák, M}, title = {SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID.}, journal = {Therapeutic advances in infectious disease}, volume = {8}, number = {}, pages = {20499361211048572}, pmid = {34659752}, issn = {2049-9361}, abstract = {Over 10% of COVID-19 convalescents report post-COVID-19 complications, namely, 'long COVID' or 'post-COVID syndrome,' including a number of neuro-psychiatric symptoms. The pathophysiology of COVID-19 in the central nervous system is poorly understood but may represent post-COVID injury, ongoing sterile maladaptive inflammation, or SARS-CoV-2 persistence. We describe a long COVID patient with SARS-CoV-2 RNA in the cerebrospinal fluid, which seems important, specifically due to recent reports of gray matter volume loss in COVID-19 patients. Further studies of SARS-CoV2 RNA, markers of inflammation, and neuronal damage in the CSF of patients with long COVID would be useful and should address whether the CNS can serve as a reservoir of SARS-CoV-2, clarify the pathway by which COVID-19 contributes to CNS dysfunction, and how best to therapeutically address it.}, } @article {pmid34659259, year = {2021}, author = {Kumar, S and Çalışkan, DM and Janowski, J and Faist, A and Conrad, BCG and Lange, J and Ludwig, S and Brunotte, L}, title = {Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {752227}, pmid = {34659259}, issn = {1664-3224}, mesh = {Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/*therapeutic use ; COVID-19/pathology/prevention & control ; COVID-19 Vaccines/*immunology ; Humans ; SARS-CoV-2/*drug effects/immunology ; Vaccination ; *COVID-19 Drug Treatment ; }, abstract = {Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2[nd] Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper the availability of vaccines in many countries. In addition, due to the emergency of SARS-CoV-2 variants with immune escape properties towards the vaccines the global numbers of new infections as well as patients developing severe COVID-19, remains high. New studies reported that about 8% of infected individuals develop long term symptoms with strong personal restrictions on private as well as professional level, which contributes to the long socioeconomic problems caused by this pandemic. Until today, emergency use-approved treatment options for COVID-19 are limited to the antiviral Remdesivir, a nucleoside analogue targeting the viral polymerase, the glucocorticosteroide Dexamethasone as well as neutralizing antibodies. The therapeutic benefits of these treatments are under ongoing debate and clinical studies assessing the efficiency of these treatments are still underway. To identify new therapeutic treatments for COVID-19, now and by the post-pandemic era, diverse experimental approaches are under scientific evaluation in companies and scientific research teams all over the world. To accelerate clinical translation of promising candidates, repurposing approaches of known approved drugs are specifically fostered but also novel technologies are being developed and are under investigation. This review summarizes the recent developments from the lab bench as well as the clinical status of emerging therapeutic candidates and discusses possible therapeutic entry points for the treatment strategies with regard to the biology of SARS-CoV-2 and the clinical course of COVID-19.}, } @article {pmid34659245, year = {2021}, author = {Siemińska, I and Węglarczyk, K and Surmiak, M and Kurowska-Baran, D and Sanak, M and Siedlar, M and Baran, J}, title = {Mild and Asymptomatic COVID-19 Convalescents Present Long-Term Endotype of Immunosuppression Associated With Neutrophil Subsets Possessing Regulatory Functions.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {748097}, pmid = {34659245}, issn = {1664-3224}, mesh = {Adult ; Antibodies, Neutralizing/*blood ; Antibodies, Viral/blood ; Asymptomatic Infections ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/*complications/immunology/pathology ; Cell Proliferation ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/blood ; Humans ; Immunocompromised Host/immunology ; Immunoglobulin G/blood ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Myeloid-Derived Suppressor Cells/*immunology ; Neutrophils/*immunology ; SARS-CoV-2/*immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8[+] and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.}, } @article {pmid34653099, year = {2022}, author = {Pierce, JD and Shen, Q and Cintron, SA and Hiebert, JB}, title = {Post-COVID-19 Syndrome.}, journal = {Nursing research}, volume = {71}, number = {2}, pages = {164-174}, pmid = {34653099}, issn = {1538-9847}, mesh = {*COVID-19/complications ; Humans ; Mass Screening ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many individuals have reported persistent symptoms and/or complications lasting beyond 4 weeks, which is now called post-COVID-19 syndrome. SARS-CoV-2 is a respiratory coronavirus that causes COVID-19, and injury to the lungs is expected; however, there is often damage to numerous other cells and organs, leading to an array of symptoms. These long-term symptoms occur in patients with mild to severe COVID-19; currently, there is limited literature on the potential pathophysiological mechanisms of this syndrome.

OBJECTIVES: The purpose of this integrative review is to summarize and evaluate post-COVID-19 syndrome from a biological perspective.

METHODS: An integrative review was conducted using Whittemore and Knafl's methodology for literature published through August 30, 2021. The PubMed, CINAHL, and Web of Science databases were searched for articles published as of August 30, 2021, using combinations of the following key words: post-COVID-19 syndrome, post-SARS-CoV-2, long COVID-19, long COVID-19 syndrome, and pathophysiology of post-COVID-19. Data were analyzed using the constant comparison method.

RESULTS: The search generated 27,929 articles. After removing duplicates and screening abstracts and full-text reviews, we retained 68 articles and examined 54 specific articles related to the pathophysiology of post-COVID-19 syndrome. The findings from our review indicated that there were four pathophysiological categories involved: virus-specific pathophysiological variations, oxidative stress, immunologic abnormalities, and inflammatory damage.

DISCUSSION: Although studies examining the pathophysiology of post-COVID-19 syndrome are still relatively few, there is growing evidence that this is a complex and multifactorial syndrome involving virus-specific pathophysiological variations that affect many mechanisms but specifically oxidative stress, immune function, and inflammation. Further research is needed to elucidate the pathophysiology, pathogenesis, and longer term consequences involved in post-COVID-19 syndrome.}, } @article {pmid34651183, year = {2023}, author = {Pye, A and Roberts, SR and Blennerhassett, A and Iqbal, H and Beenstock, J and Iqbal, Z}, title = {A public health approach to estimating the need for long COVID services.}, journal = {Journal of public health (Oxford, England)}, volume = {45}, number = {1}, pages = {169-175}, doi = {10.1093/pubmed/fdab365}, pmid = {34651183}, issn = {1741-3850}, mesh = {Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Public Health ; Pandemics ; }, abstract = {BACKGROUND: The term 'long COVID' describes ongoing symptoms and conditions experienced by people infected with SARS-CoV-2. This paper illustrates how a public health approach was used to influence and inform the development of post-COVID services across two Integrated Care Systems (ICSs).

METHODS: A literature review was conducted between October and December 2020 to identify prevalence estimates for long COVID. The prevalence estimates were applied to locally available data on the susceptible population to estimate the number of people with long COVID. They were also used to develop a dashboard to predict fluctuations in the number of people experiencing persistent symptoms over time.

RESULTS: A substantial number of people in each ICS may have experienced persistent symptoms or complications as a result of COVID-19. In Lancashire and South Cumbria, it is estimated that 33 000 people may have experienced post-COVID-19 syndrome since the beginning of the pandemic, which will include respiratory or cardiovascular complications.

CONCLUSIONS: The findings have been valuable in informing early service developments, engaging with managers and clinicians, and supporting applications for funding at a local level. Continued attention to emergent evidence on this topic will be vital in refining estimates and supporting service planning in the longer term.}, } @article {pmid34650349, year = {2021}, author = {Di Toro, A and Bozzani, A and Tavazzi, G and Urtis, M and Giuliani, L and Pizzoccheri, R and Aliberti, F and Fergnani, V and Arbustini, E}, title = {Long COVID: long-term effects?.}, journal = {European heart journal supplements : journal of the European Society of Cardiology}, volume = {23}, number = {Suppl E}, pages = {E1-E5}, pmid = {34650349}, issn = {1520-765X}, abstract = {The term Long COVID (or Post COVID) describes a condition characterized by persistence of symptoms for at least 12 weeks after the onset of COVID-19. It may last several months but the duration is still matter of observation. The symptoms and the clinical manifestations are clinically heterogeneous and suggesting involvement of multi-organs/systems, including the cardiovascular system. The general recurrent symptoms include fatigue, breathlessness, myalgia, headache, loss of memory, and impaired concentration. Patients report loss of their previous psychophysical performance. Cardiovascular involvement manifests with common symptoms such as palpitations and chest pain, and, less commonly, with events such as late arterial and venous thromboembolisms, heart failure episodes, strokes or transient ischaemic attack, 'myo-pericarditis'. The diagnostic criteria are mainly based on the narrative of the patients. Measurable biomarkers or instrumental findings or clinical events are not yet framed in a shared diagnostic framework. The open question for clinicians and researchers is whether biomarkers, electrocardiogram, non-invasive imaging, and clinical monitoring should be included in a shared diagnostic protocol aimed at defining the diagnostic path and protecting patients at risk of unexpected events.}, } @article {pmid34649946, year = {2022}, author = {Dressing, A and Bormann, T and Blazhenets, G and Schroeter, N and Walter, LI and Thurow, J and August, D and Hilger, H and Stete, K and Gerstacker, K and Arndt, S and Rau, A and Urbach, H and Rieg, S and Wagner, D and Weiller, C and Meyer, PT and Hosp, JA}, title = {Neuropsychologic Profiles and Cerebral Glucose Metabolism in Neurocognitive Long COVID Syndrome.}, journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine}, volume = {63}, number = {7}, pages = {1058-1063}, pmid = {34649946}, issn = {1535-5667}, mesh = {*COVID-19/complications/psychology ; *Cerebrum/metabolism ; Fatigue ; Fluorodeoxyglucose F18/metabolism ; *Glucose/metabolism ; Humans ; Middle Aged ; Neuropsychological Tests ; Positron-Emission Tomography ; Post-Acute COVID-19 Syndrome ; }, abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, Long COVID syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients with long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurologic counseling with neurocognitive symptoms persisting for more than 3 mo after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31; age, 53.6 ± 2.0 y) in the long-term phase after COVID-19 (202 ± 58 d after positive PCR) were assessed with a neuropsychologic test battery. Cerebral [18]F-FDG PET imaging was performed in 14 of 31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychologic test battery showed no impairment, but deficits (z score < -1.5) were present on a single-patient level mainly in the domain of visual memory (in 7/31; other domains ≤ 2/31). Mean Montreal Cognitive Assessment performance (27/30 points) was above the cutoff value for detection of cognitive impairment (<26 points), although 9 of 31 patients performed slightly below this level (23-25 points). In the subgroup of patients who underwent [18]F-FDG PET, we found no significant changes of regional cerebral glucose metabolism. Conclusion: Long COVID patients self-report uniform symptoms hampering their ability to work in a relevant fraction. However, cognitive testing showed minor impairments only on a single-patient level approximately 6 mo after the infection, whereas functional imaging revealed no distinct pathologic changes. This clearly deviates from previous findings in subacute COVID-19 patients, suggesting that underlying neuronal causes are different and possibly related to the high prevalence of fatigue.}, } @article {pmid34648081, year = {2021}, author = {Tizenberg, BN and Brenner, LA and Lowry, CA and Okusaga, OO and Benavides, DR and Hoisington, AJ and Benros, ME and Stiller, JW and Kessler, RC and Postolache, TT}, title = {Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19.}, journal = {Current psychiatry reports}, volume = {23}, number = {10}, pages = {68}, pmid = {34648081}, issn = {1535-1645}, mesh = {Brain ; *COVID-19 ; Central Nervous System ; Humans ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {PURPOSE OF REVIEW: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology.

RECENT FINDINGS: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.}, } @article {pmid34646643, year = {2021}, author = {Nazir, T and Chit Su, HM and Mann, P and Clancy, N and Kargar, L}, title = {Long COVID Syndrome and Takotsubo Cardiomyopathy: An Unwelcome Combination.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e17590}, pmid = {34646643}, issn = {2168-8184}, abstract = {Since the report of the first case from China in late 2019, the coronavirus disease (COVID-19) has spread very rapidly through the countries and regions leaving a trail of devastation in its path, everywhere. Although COVID-19 is primarily a respiratory illness mainly affecting the lungs; involvement of other organs including the cardiovascular system has been widely recognized. Whilst COVID-19 is an acute illness for a majority of cases; some of the debilitating virus-related symptoms can last for weeks and months, and are collectively termed as long COVID syndrome. Several published reports have described an association between acute COVID-19 illness and cardiac complications such as myocarditis and Takotsubo cardiomyopathy. However, little is known about any link between long COVID syndrome and the cardiac disease. We describe the case of a middle-aged woman with long COVID syndrome who presented with central chest pain and breathlessness. Her initial investigations showed an elevated cardiac troponin I and ischemic changes on 12 lead ECG. She was initially treated for non-ST elevation myocardial infarction. A subsequent coronary angiogram showed unobstructed coronary vessels and left ventricle (LV) gram demonstrated apical LV ballooning. She was managed conservatively and was discharged home following her clinical improvement. This case highlights the importance of holistic assessment of patients presenting with chest pain with the background of long COVID syndrome. It also outlines an emergent need to better understand pathophysiological mechanisms that underpin the development of cardiac complications in those with COVID-19 and long COVID syndrome.}, } @article {pmid34646278, year = {2021}, author = {Bellucci, G and Rinaldi, V and Buscarinu, MC and Reniè, R and Bigi, R and Pellicciari, G and Morena, E and Romano, C and Marrone, A and Mechelli, R and Salvetti, M and Ristori, G}, title = {Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {755333}, pmid = {34646278}, issn = {1664-3224}, mesh = {Animals ; COVID-19/epidemiology/*immunology/prevention & control/virology ; COVID-19 Vaccines/administration & dosage ; Host-Pathogen Interactions ; Humans ; Multiple Sclerosis/epidemiology/*immunology/virology ; Prognosis ; Risk Factors ; SARS-CoV-2/*immunology/pathogenicity ; Vaccination ; }, abstract = {Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host's genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host's response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.}, } @article {pmid34642875, year = {2021}, author = {Horn, A and Krist, L and Lieb, W and Montellano, FA and Kohls, M and Haas, K and Gelbrich, G and Bolay-Gehrig, SJ and Morbach, C and Reese, JP and Störk, S and Fricke, J and Zoller, T and Schmidt, S and Triller, P and Kretzler, L and Rönnefarth, M and Von Kalle, C and Willich, SN and Kurth, F and Steinbeis, F and Witzenrath, M and Bahmer, T and Hermes, A and Krawczak, M and Reinke, L and Maetzler, C and Franzenburg, J and Enderle, J and Flinspach, A and Vehreschild, J and Schons, M and Illig, T and Anton, G and Ungethüm, K and Finkenberg, BC and Gehrig, MT and Savaskan, N and Heuschmann, PU and Keil, T and Schreiber, S}, title = {Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).}, journal = {Infection}, volume = {49}, number = {6}, pages = {1277-1287}, pmid = {34642875}, issn = {1439-0973}, support = {01KX2021//bundesministerium für bildung und forschung/ ; }, mesh = {*COVID-19/complications ; Humans ; Pandemics ; *Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany.

METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained.

RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once.

CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity.

TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).}, } @article {pmid34642697, year = {2021}, author = {Nussenblatt, V and Roder, AE and Das, S and de Wit, E and Youn, JH and Banakis, S and Mushegian, A and Mederos, C and Wang, W and Chung, M and Pérez-Pérez, L and Palmore, T and Brudno, JN and Kochenderfer, JN and Ghedin, E}, title = {Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {34642697}, abstract = {BACKGROUND: B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution.

METHODS: Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patient's original presentation and 10 months later.

RESULTS: Over the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples-reflecting the heterogeneity of the initial infection-were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection.

CONCLUSIONS: The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants.

SUMMARY: We report an immunocompromised patient with persistent symptomatic SARS-CoV-2 infection for 335 days. During this time, the virus accumulated a unique in-frame deletion in the spike, and a complete deletion of ORF7b and ORF8 which is the first report of its kind in an immunocompromised patient.}, } @article {pmid34640471, year = {2021}, author = {Och, A and Tylicki, P and Polewska, K and Puchalska-Reglińska, E and Parczewska, A and Szabat, K and Biedunkiewicz, B and Dębska-Ślizień, A and Tylicki, L}, title = {Persistent Post-COVID-19 Syndrome in Hemodialyzed Patients-A Longitudinal Cohort Study from the North of Poland.}, journal = {Journal of clinical medicine}, volume = {10}, number = {19}, pages = {}, pmid = {34640471}, issn = {2077-0383}, abstract = {BACKGROUND: After recovery from COVID-19, patients frequently face so-called "Post-COVID-19 Syndrome" defined by clusters of persistent symptoms lasting for >12 weeks which may arise from any system in the body. The long-term health consequences of COVID-19 in maintenance hemodialyzed (HD) patients remain to be investigated.

METHODS: In this longitudinal cohort study we described the health consequences in HD patients requiring hospitalization due to COVID-19. They were interviewed three and six months (M3 and M6) after discharge with a series of standardized questionnaires.

RESULTS: Of 144 HD patients discharged from the 7th Naval Hospital in Gdansk, 79 participants were enrolled, 39 m (49.4%) and 40 f (50.6%) with a median age of 70.0 (64.0-76.5) and an HD vintage of 40 months (17.5-88). After discharge, 93.7% and 81% reported at least one persistent symptom at M3 and M6, respectively. The most common symptoms were fatigue or muscle weakness (60.76% and 47.04%) and palpitations (40.51% and 30.14%). Dyspnea with an mMRC scale grade of at least 1 was reported by 21.5% before infection, and by 43.03% and 34.25% at M3 and M6, respectively. A decrease in the quality of life was reported in all domains of the EQ-5D-5L questionnaire but mainly in the pain/discomfort and anxiety dimensions. Mean EQ-VAS scores were 69.05, 61.58 and 64.38, respectively.

CONCLUSION: Our study showed that HD patients may still experience persistent symptoms six months after recovery from COVID-19, which can further reduce their already poor health-related quality of life. This study highlights the need for long-term follow-up on these patients for diagnostic and rehabilitation programs.}, } @article {pmid34638785, year = {2021}, author = {Nataf, S and Pays, L}, title = {Molecular Insights into SARS-CoV2-Induced Alterations of the Gut/Brain Axis.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34638785}, issn = {1422-0067}, mesh = {Angiotensin-Converting Enzyme 2/genetics ; Aromatic-L-Amino-Acid Decarboxylases/genetics ; Brain/metabolism/*pathology ; COVID-19/*complications/genetics/pathology ; Cells, Cultured ; Enterocytes/metabolism/pathology ; *Gene Expression Regulation ; Humans ; Intestine, Small/metabolism/*pathology ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {For a yet unknown reason, a substantial share of patients suffering from COVID-19 develop long-lasting neuropsychiatric symptoms ranging from cognitive deficits to mood disorders and/or an extreme fatigue. We previously reported that in non-neural cells, angiotensin-1 converting enzyme 2 (ACE2), the gene coding for the SARS-CoV2 host receptor, harbors tight co-expression links with dopa-decarboxylase (DDC), an enzyme involved in the metabolism of dopamine. Here, we mined and integrated data from distinct human expression atlases and found that, among a wide range of tissues and cells, enterocytes of the small intestine express the highest expression levels of ACE2, DDC and several key genes supporting the metabolism of neurotransmitters. Based on these results, we performed co-expression analyses on a recently published set of RNA-seq data obtained from SARS-CoV2-infected human intestinal organoids. We observed that in SARS-CoV2-infected enterocytes, ACE2 co-regulates not only with DDC but also with a specific group of genes involved in (i) the dopamine/trace amines metabolic pathway, (ii) the absorption of microbiota-derived L-DOPA and (iii) the absorption of neutral amino acids serving as precursors to neurotransmitters. We conclude that in patients with long COVID, a chronic infection and inflammation of small intestine enterocytes might be indirectly responsible for prolonged brain alterations.}, } @article {pmid34636103, year = {2022}, author = {Guedj, E and Campion, JY and Horowitz, T and Barthelemy, F and Cammilleri, S and Ceccaldi, M}, title = {The impact of COVID-19 lockdown on brain metabolism.}, journal = {Human brain mapping}, volume = {43}, number = {2}, pages = {593-597}, pmid = {34636103}, issn = {1097-0193}, mesh = {Aged ; Aged, 80 and over ; Brain/diagnostic imaging/*metabolism ; *COVID-19/complications/metabolism ; Emotions ; Exercise ; Female ; Fluorodeoxyglucose F18 ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Motor Cortex/diagnostic imaging/metabolism ; Nerve Net/metabolism ; *Pandemics ; Positron-Emission Tomography ; *Quarantine ; Radiopharmaceuticals ; Retrospective Studies ; Social Isolation ; Somatosensory Cortex/diagnostic imaging/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {This study aims to evaluate the impact of French national lockdown of 55 days on brain metabolism of patients with neurological disorders. Whole-brain voxel-based PET analysis was used to correlate [18] F-FDG metabolism to the number of days after March 17, 2020 (in 95 patients; mean age: 54.3 years ± 15.7; 59 men), in comparison to the same period in 2019 before the SARS-CoV-2 outbreak (in 212 patients; mean age: 59.5 years ± 15.8; 114 men), and to the first 55 days of deconfinement (in 188 patients; mean age: 57.5 years ± 16.5; 93 men). Lockdown duration was negatively correlated to the metabolism of the sensory-motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap was found with the reported pattern of hypometabolism in long COVID (<9%). Restriction of physical activities, and possible related deconditioning, and social isolation may lead to functional disturbances of sensorimotor and emotional brain networks. Of note, this metabolic pattern seems distinct to those reported in long COVID. Further longitudinal studies with longer follow-up are needed to evaluate clinical consequences and relationships on cognitive and mental health against functional deactivation hypothesis, and to extend these findings to healthy subjects in the context of lockdown.}, } @article {pmid34632070, year = {2021}, author = {Ausín-García, C and Cervilla-Muñoz, E and Millán-Nuñez-Cortés, J}, title = {Long-term consequences of SARS-COV2 infection: Long-Covid patterns and possible public health implications.}, journal = {Medicina clinica (English ed.)}, volume = {157}, number = {7}, pages = {e293-e294}, pmid = {34632070}, issn = {2387-0206}, } @article {pmid34631916, year = {2021}, author = {Sandler, CX and Wyller, VBB and Moss-Morris, R and Buchwald, D and Crawley, E and Hautvast, J and Katz, BZ and Knoop, H and Little, P and Taylor, R and Wensaas, KA and Lloyd, AR}, title = {Long COVID and Post-infective Fatigue Syndrome: A Review.}, journal = {Open forum infectious diseases}, volume = {8}, number = {10}, pages = {ofab440}, pmid = {34631916}, issn = {2328-8957}, abstract = {Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.}, } @article {pmid34629462, year = {2021}, author = {Parums, DV}, title = {Editorial: Multisystem Inflammatory Syndrome in Adults (MIS-A) and the Spectrum of COVID-19.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e935005}, pmid = {34629462}, issn = {1643-3750}, mesh = {COVID-19/*complications/genetics/immunology ; Cytokine Release Syndrome/etiology/genetics/immunology ; Humans ; Systemic Inflammatory Response Syndrome/*etiology/genetics/immunology ; }, abstract = {Recent studies on the pathogenesis and clinical spectrum of human disease following infection with the new human pathogen, SARS-CoV-2, have identified the varied presentations and sequelae of COVID-19. Acute 'cytokine storm' in severe COVID-19 results in multiorgan damage due to vascular hyperpermeability, edema, and hypercoagulation. The long-term consequences of infection from SARS-CoV-2 include long COVID. or post-COVID syndrome, and multisystem inflammatory syndrome in children (MIS-C). Several case reports of multisystem inflammatory syndrome in adults (MIS-A) have shown the presentation at more than four weeks after initial infection with SARS-CoV-2 in adults more than 21 years of age. In September 2021, a published systematic review of the literature identified 221 patients with MIS-A, representing the most comprehensive clinical study to date. MIS-A occurs in the post-acute COVID-19 period. The pathogenesis may involve a dysregulated antibody-mediated immune response, similar to MIS-C. Therefore, patients with MIS-A may respond to supportive therapies that control hyperinflammation. This Editorial aims to describe MIS-A and discuss COVID-19 as a spectrum of hyperinflammatory disease in terms of severity, extent, duration, and patient age.}, } @article {pmid34621523, year = {2020}, author = {Michelen, M and Cheng, V and Manoharan, L and Elkheir, N and Dagens, D and Hastie, C and O'Hara, M and Suett, JC and Dahmash, D and Bugaeva, P and Rigby, I and Munblit, D and Harriss, E and Burls, A and Foote, C and Scott, J and Carson, G and Olliaro, P and Sigfrid, L and Stavropoulou, C}, title = {What are the long-term symptoms and complications of COVID-19: a protocol for a living systematic review.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {1455}, pmid = {34621523}, issn = {2046-1402}, mesh = {Anxiety ; *COVID-19 ; Disease Progression ; Heart ; Humans ; SARS-CoV-2 ; }, abstract = {Although the majority of people with Covid-19 will experience mild to moderate symptoms and will recover fully, there is now increasing evidence that a significant proportion will experience persistent symptoms for months after the acute phase of the illness. These symptoms include, among others, fatigue, problems breathing, lack of smell and taste, headaches, and depression and anxiety. It is also clear the virus has lasting fluctuating multiorgan sequelae, including affecting not only the respiratory system but also the heart, liver, and nervous system. We present a protocol for a living systematic review that aims to synthesize the evidence on the prevalence and characteristics of post-acute COVID-19. The living systematic review will be updated regularly, approximately every 6 months, as new evidence emerges. We will include studies that follow up at least 100 people with Covid-19 at 12 or more weeks post Covid-19 onset, with no restrictions regarding country, setting, or language. We will use descriptive statistics and, for outcomes reported in two or more studies, we will use meta-analyses to estimate prevalence with 95% confidence intervals (CIs) using the exact method. Heterogeneity between estimates will be assessed using the I2 statistic. Our findings will also be presented as infographics to facilitate transcription to lay audiences. Ultimately, we aim to support the work of policy makers, practitioners, and patients when planning rehabilitation for those recovering from Covid-19. The protocol has been registered with PROSPERO (CRD42020211131, 25/09/2020).}, } @article {pmid34626096, year = {2021}, author = {Baig, AM}, title = {Chronic long-COVID syndrome: A protracted COVID-19 illness with neurological dysfunctions.}, journal = {CNS neuroscience & therapeutics}, volume = {27}, number = {12}, pages = {1433-1436}, pmid = {34626096}, issn = {1755-5949}, mesh = {COVID-19/*complications/physiopathology/virology ; Humans ; Inflammation/etiology/physiopathology ; Nervous System Diseases/etiology/*physiopathology ; Neurodegenerative Diseases/etiology/physiopathology ; Viral Load ; Post-Acute COVID-19 Syndrome ; }, abstract = {After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in long-COVID syndrome.}, } @article {pmid34620202, year = {2021}, author = {Lemhöfer, C and Sturm, C and Loudovici-Krug, D and Best, N and Gutenbrunner, C}, title = {The impact of Post-COVID-Syndrome on functioning - results from a community survey in patients after mild and moderate SARS-CoV-2-infections in Germany.}, journal = {Journal of occupational medicine and toxicology (London, England)}, volume = {16}, number = {1}, pages = {45}, pmid = {34620202}, issn = {1745-6673}, abstract = {BACKGROUND: In COVID-19 survivors a relatively high number of long-term symptoms have been observed. Besides impact on quality of life, these symptoms (now called Post-COVID-Syndrome) may have an impact on functioning and may also hinder to participation in social life in affected people. However, little is known about developing such syndrome a for patients with mild and moderate COVID-19 who did not need hospitalization or intensive care.

METHODS: A cross-sectional study in 1027 patients with mild or moderate COVID-19 was performed in two communities in Bavaria, Germany. The Rehabilitation-Needs-Survey (RehabNeS) including the Short Form 36 Health Survey (SF-36) on health-related quality of life, was used. Descriptive statistics were calculated.

RESULTS: In all, 97.5% of patients reported one symptom in the infection stage, such as fatigue, respiratory problems, limitations of the senses of taste and smell, fear and anxiety and other symptoms. In this time period, 84.1% of the participants experienced activity limitations and participation restrictions such as carrying out daily routines, handling stress, getting household tasks done, caring for/supporting others, and relaxing and leisure concerns. In all, 61.9% of participants reported persisting symptoms more than 3 months after infection. These were fatigue, sleep disturbances, respiratory problems, pain, fear and anxiety, and restrictions in movement; 49% of the participants reported activity limitations and participation restrictions. Predominately, these were handling stress, carrying out daily routines, looking after one's health, relaxing and leisure activities and doing house work. The impacts on quality of life and vocational performance were rather low.

CONCLUSION: The results show that long-term symptoms after mild and moderate COVID-19 are common and lead to limitations of activities and participation. However, it seems that in most cases they are not severe and do not lead to frequent or serious issues with quality of life or work ability.}, } @article {pmid34619336, year = {2022}, author = {Bucciarelli, V and Nasi, M and Bianco, F and Seferovic, J and Ivkovic, V and Gallina, S and Mattioli, AV}, title = {Depression pandemic and cardiovascular risk in the COVID-19 era and long COVID syndrome: Gender makes a difference.}, journal = {Trends in cardiovascular medicine}, volume = {32}, number = {1}, pages = {12-17}, pmid = {34619336}, issn = {1873-2615}, mesh = {*COVID-19/complications/psychology ; *Cardiovascular Diseases/diagnosis/epidemiology ; *Depression/diagnosis/epidemiology ; Female ; Heart Disease Risk Factors ; Humans ; Male ; Pandemics ; Risk Factors ; *Sex Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {The ongoing COVID-19 pandemic highlighted a significant interplay between cardiovascular disease (CVD), COVID-19 related inflammatory status, and depression. Cardiovascular (CV) injury is responsible for a substantial percentage of COVID-19 deaths while COVID-19 social restrictions emerged as a non-negligible risk factor for CVD as well as a variety of mental health issues, and in particular, depression. Inflammation seems to be a shared condition between these two disorders. Gender represents a potential modifying factor both in CVD and depression, as well as in COVID-19 short- and long-term outcomes, particularly in cases involving long-term COVID complications. Results from emerging studies indicate that COVID-19 pandemic affected male and female populations in different ways. Women seem to experience less severe short-term complications but suffer worse long-term COVID complications, including depression, reduced physical activity, and deteriorating lifestyle habits, all of which may impact CV risk. Here, we summarize the current state of knowledge about the interplay between COVID-19, depression, and CV risk in women.}, } @article {pmid34617371, year = {2021}, author = {Décary, S and Brown, D and Davenport, TE and Ngeh, E and , }, title = {Does the Collaborative Consensus Guidance Statement put the exercise "cart" before the pacing and pharmacological "horses" in long COVID/PASC?.}, journal = {PM & R : the journal of injury, function, and rehabilitation}, volume = {13}, number = {12}, pages = {1437-1438}, doi = {10.1002/pmrj.12718}, pmid = {34617371}, issn = {1934-1563}, mesh = {Animals ; *COVID-19/complications ; Consensus ; Horses ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34614444, year = {2021}, author = {Bertin, D and Kaphan, E and Weber, S and Babacci, B and Arcani, R and Faucher, B and Ménard, A and Brodovitch, A and Mege, JL and Bardin, N}, title = {Persistent IgG anticardiolipin autoantibodies are associated with post-COVID syndrome.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {113}, number = {}, pages = {23-25}, pmid = {34614444}, issn = {1878-3511}, mesh = {*Antibodies, Anticardiolipin ; Autoantibodies ; *COVID-19/complications ; Female ; Humans ; Immunoglobulin G ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistence of various symptoms in patients who have recovered from coronavirus disease 2019 (COVID-19) was recently defined as 'long COVID' or 'post-COVID syndrome' (PCS). This article reports a case of a 58-year-old woman who, although recovering from COVID-19, had novel and persistent symptoms including neurological complications that could not be explained by any cause other than PCS. In addition to a low inflammatory response, persistence of immunoglobulin G anticardiolipin autoantibody positivity and eosinopenia were found 1 year after acute COVID-19 infection, both of which have been defined previously as independent factors associated with the severity of COVID-19. The pathophysiological mechanism of PCS is unknown, but the possibility of persistence of the virus, especially in the nervous system, could be suggested with a post-infectious inflammatory or autoimmune reaction.}, } @article {pmid34611512, year = {2021}, author = {Arentz, S and Hunter, J and Khamba, B and Mravunac, M and Lee, Z and Alexander, K and Lauche, R and Goldenberg, J and Myers, SP}, title = {Honeybee products for the treatment and recovery from viral respiratory infections including SARS-COV-2: A rapid systematic review.}, journal = {Integrative medicine research}, volume = {10}, number = {Suppl}, pages = {100779}, pmid = {34611512}, issn = {2213-4220}, abstract = {BACKGROUND: This rapid review systematically evaluated the effects of honeybee products compared to controls for the prevention, duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children.

METHODS: Cochrane rapid review methods were applied. Four English databases plus preprint servers and trial registries were searched for randomized controlled trials (RCTs). The evidence was appraised and synthesized using RoB 2.0 and GRADE.

RESULTS: 27 results were derived from 9 RCTs that included 674 adults and 781 children. In hospitalized adults with SARS-CoV-2, propolis plus usual-care compared to usual-care alone reduced the risk of shock, respiratory failure and kidney injury and duration of hospital admission. Honey was less effective than Guaifenesin for reducing cough severity at 60-minutes in adults with non-specific acute viral RTIs. Compared to coffee, honey plus coffee, and honey alone reduced the severity of post-infectious cough in adults. Honey reduced the duration of cough in children compared to placebo and salbutamol; and the global impact of nocturnal cough after one night compared to usual-care alone and pharmaceutical cough medicines.

CONCLUSION: More studies are needed to robustly assess honeybee's role in SARS-CoV-2 and non-specific viral respiratory infections.

PROTOCOL REGISTRATION: PROSPERO: CRD42020193847.}, } @article {pmid34611034, year = {2022}, author = {Glynne, P and Tahmasebi, N and Gant, V and Gupta, R}, title = {Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {70}, number = {1}, pages = {61-67}, pmid = {34611034}, issn = {1708-8267}, mesh = {Adult ; Aged ; COVID-19/*complications/diagnosis/*immunology ; Female ; Histamine ; Histamine Antagonists/*therapeutic use ; Humans ; Male ; Middle Aged ; SARS-CoV-2/immunology ; T-Lymphocyte Subsets/immunology ; *T-Lymphocytes ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID is characterized by the emergence of multiple debilitating symptoms following SARS-CoV-2 infection. Its etiology is unclear and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRAs) suggest a histamine-dependent mechanism that is distinct from anaphylaxis, possibly mediated by T cells, which are also regulated by histamine. T cell perturbations have been previously reported in post-viral syndromes, but the T cell landscape in patients who have recovered from mild COVID-19 and its relationship to both long COVID symptoms and any symptomatic response to HRA remain underexplored. We addressed these questions in an observational study of 65 individuals who had recovered from mild COVID-19. Participants were surveyed between 87 and 408 days after the onset of acute symptoms; none had required hospitalization, 16 had recovered uneventfully, and 49 had developed long COVID. Symptoms were quantified using a structured questionnaire and T cell subsets enumerated in a standard diagnostic assay. Patients with long-COVID had reduced CD4+ and CD8+ effector memory (EM) cell numbers and increased PD-1 (programmed cell death protein 1) expression on central memory (CM) cells, whereas the asymptomatic participants had reduced CD8+ EM cells only and increased CD28 expression on CM cells. 72% of patients with long COVID who received HRA reported clinical improvement, although T cell profiling did not clearly distinguish those who responded to HRA. This study demonstrates that T cell perturbations persist for several months after mild COVID-19 and are associated with long COVID symptoms.}, } @article {pmid34609841, year = {2021}, author = {Najafloo, R and Majidi, J and Asghari, A and Aleemardani, M and Kamrava, SK and Simorgh, S and Seifalian, A and Bagher, Z and Seifalian, AM}, title = {Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments.}, journal = {ACS chemical neuroscience}, volume = {12}, number = {20}, pages = {3795-3805}, doi = {10.1021/acschemneuro.1c00477}, pmid = {34609841}, issn = {1948-7193}, mesh = {Anosmia ; *COVID-19/complications ; Humans ; *Olfaction Disorders ; SARS-CoV-2 ; Smell ; Post-Acute COVID-19 Syndrome ; }, abstract = {The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.}, } @article {pmid34607799, year = {2021}, author = {Nurek, M and Rayner, C and Freyer, A and Taylor, S and Järte, L and MacDermott, N and Delaney, BC and , }, title = {Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {e815-e825}, pmid = {34607799}, issn = {1478-5242}, support = {FS/17/16/32560/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {*COVID-19/complications/diagnosis/therapy ; Consensus ; Delphi Technique ; Humans ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: In the absence of research into therapies and care pathways for long COVID, guidance based on 'emerging experience' is needed.

AIM: To provide a rapid expert guide for GPs and long COVID clinical services.

DESIGN AND SETTING: A Delphi study was conducted with a panel of primary and secondary care doctors.

METHOD: Recommendations were generated relating to the investigation and management of long COVID. These were distributed online to a panel of UK doctors (any specialty) with an interest in, lived experience of, and/or experience treating long COVID. Over two rounds of Delphi testing, panellists indicated their agreement with each recommendation (using a five-point Likert scale) and provided comments. Recommendations eliciting a response of 'strongly agree', 'agree', or 'neither agree nor disagree' from 90% or more of responders were taken as showing consensus.

RESULTS: Thirty-three clinicians representing 14 specialties reached consensus on 35 recommendations. Chiefly, GPs should consider long COVID in the presence of a wide range of presenting features (not limited to fatigue and breathlessness) and exclude differential diagnoses where appropriate. Detailed history and examination with baseline investigations should be conducted in primary care. Indications for further investigation and specific therapies (for myocarditis, postural tachycardia syndrome, mast cell disorder) include hypoxia/desaturation, chest pain, palpitations, and histamine-related symptoms. Rehabilitation should be individualised, with careful activity pacing (to avoid relapse) and multidisciplinary support.

CONCLUSION: Long COVID clinics should operate as part of an integrated care system, with GPs playing a key role in the multidisciplinary team. Holistic care pathways, investigation of specific complications, management of potential symptom clusters, and tailored rehabilitation are needed.}, } @article {pmid34603261, year = {2021}, author = {Hilpert, K and Mikut, R}, title = {Is There a Connection Between Gut Microbiome Dysbiosis Occurring in COVID-19 Patients and Post-COVID-19 Symptoms?.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {732838}, pmid = {34603261}, issn = {1664-302X}, } @article {pmid34603189, year = {2021}, author = {Boesl, F and Audebert, H and Endres, M and Prüss, H and Franke, C}, title = {A Neurological Outpatient Clinic for Patients With Post-COVID-19 Syndrome - A Report on the Clinical Presentations of the First 100 Patients.}, journal = {Frontiers in neurology}, volume = {12}, number = {}, pages = {738405}, pmid = {34603189}, issn = {1664-2295}, abstract = {Background and Objectives: Neurological and psychiatric symptoms are frequent in patients with post-COVID-19 syndrome (PCS). Here, we report on the clinical presentation of the first 100 patients who presented to our PCS Neurology outpatient clinic ≥12 weeks after the acute infection with SARS-CoV-2. To date, PCS is only defined by temporal connection to SARS-CoV-2 infection. Identification of clinical phenotypes and subgroups of PCS is urgently needed. Design: We assessed clinical data of our first 100 ambulatory patients regarding clinical presentations; self-questionnaires focusing on daytime sleepiness, mood, and fatigue; and a screening assessment for detecting cognitive impairment. Results: A total of 89% of the patients presenting to the Neurology outpatient clinic had an initially mild course of COVID-19 and had not been hospitalized. The majority of the patients were female (67 vs. 33% male). The most frequent symptom reported was cognitive impairment (72%). There were 30% of patients who reported cognitive deficits and scored below 26 points on the Montreal Cognitive Assessment Scale. Fatigue (67%), headache (36%), and persisting hyposmia (36%) were also frequently reported; 5.5% of all patients showed signs of severe depression. Discussion: To our knowledge, this is the first report of patient data of a PCS Neurology outpatient clinic. Neurological sequelae also exist for more than 3 months after mainly mild SARS-CoV-2 acute infections. The reported symptoms are in accordance with recently published data of hospitalized patients.}, } @article {pmid34601388, year = {2021}, author = {Lechner-Scott, J and Levy, M and Hawkes, C and Yeh, A and Giovannoni, G}, title = {Long COVID or post COVID-19 syndrome.}, journal = {Multiple sclerosis and related disorders}, volume = {55}, number = {}, pages = {103268}, pmid = {34601388}, issn = {2211-0356}, mesh = {*COVID-19/complications ; Fatigue ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34601116, year = {2022}, author = {Doyle, MF}, title = {Central nervous system outcomes of COVID-19.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {241}, number = {}, pages = {41-51}, pmid = {34601116}, issn = {1878-1810}, support = {R01 AG067457/AG/NIA NIH HHS/United States ; }, mesh = {COVID-19/*complications/virology ; Central Nervous System/*physiopathology ; Humans ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected an estimated 200 million people with over 4 million deaths. Although COVID-19, the disease caused by the SARS-CoV-2 virus, is primarily a respiratory disease, an increasing number of neurologic symptoms have been reported. Some of these symptoms, such as loss of smell or taste, are mild and non-life threatening, while others, such as stroke or seizure, are more critical. Many of these symptoms remain long after the acute illness has passed, a phenomenon known as "long COVID" or postacute sequelae of SARS-CoV-2 infection (PASC). Neurological symptoms can be difficult to study due to the complexity of the central and peripheral nervous system. These neurologic symptoms can be difficult to identify and quantitate. This narrative review will describe approaches for assessing neurologic manifestations of COVID-19, with examples of the data they provide, as well as some directions for future research to aid in understanding the pathophysiology of COVID-19-related neurological implications.}, } @article {pmid34592419, year = {2021}, author = {Dudouet, P and Cammilleri, S and Guedj, E and Jacquier, A and Raoult, D and Eldin, C}, title = {Aortic [18]F-FDG PET/CT hypermetabolism in patients with long COVID: a retrospective study.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {12}, pages = {1873-1875}, pmid = {34592419}, issn = {1469-0691}, mesh = {*COVID-19/complications ; *Fluorodeoxyglucose F18 ; Humans ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34583690, year = {2021}, author = {Jandhyala, R}, title = {Design, validation and implementation of the post-acute (long) COVID-19 quality of life (PAC-19QoL) instrument.}, journal = {Health and quality of life outcomes}, volume = {19}, number = {1}, pages = {229}, pmid = {34583690}, issn = {1477-7525}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; *Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The novel coronavirus (SARS-CoV-2) has led to a global pandemic, resulting in a disease termed COVID-19, which commonly presents in adults as a typical infection of the upper respiratory tract. Although the disease is often acute, one in ten patients can continue to be affected for weeks or months, resulting in a state called long COVID. Existing evidence suggests there are no patient-centred instruments for capturing the impact of long COVID on the quality of life of people affected.

METHODS: The Jandhyala Method was used to identify indicators of long COVID quality of life. The resulting post-acute (long) COVID-19 Quality of Life (PAC-19QoL) instrument was validated with a control group of unaffected participants and finally implemented in the dedicated patient registry, PAC-19QoLReg.

PARTICIPANTS: 15 participants suffering from long COVID, who have been positively diagnosed with COVID-19, either via diagnostic or antibody tests and a validation control group of 16 healthy participants who have not suffered from COVID-19.

MAIN OUTCOME MEASURES: Indicators submitted by participants with long COVID that address the specific impact of the illness on their quality of life.

RESULTS: Forty-four Quality of Life Indicators (QoLI) across four domains, namely, psychological, physical, social, and work, were agreed by the participants with long COVID to be relevant for the assessment of their quality of life (CI > 0.5). The validation stage identified 35/44 QoLIs that differentiated between the two groups, with a statistically significant difference between the mean QoLI Likert Scores (p < 0.05).

CONCLUSIONS: The PAC-19QoL instrument and PAC-19QoLReg prospective observational cohort clinical study will enable an understanding of disease progression, on and off treatment, on the quality of life of patients with long COVID beyond simple symptomatology.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04586413; 14th October 2020.}, } @article {pmid34582441, year = {2021}, author = {Taquet, M and Dercon, Q and Luciano, S and Geddes, JR and Husain, M and Harrison, PJ}, title = {Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.}, journal = {PLoS medicine}, volume = {18}, number = {9}, pages = {e1003773}, pmid = {34582441}, issn = {1549-1676}, support = {206330/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Aged ; COVID-19/*complications/epidemiology ; Cohort Studies ; Dyspnea/epidemiology/etiology ; Fatigue/epidemiology/etiology ; Female ; Gastrointestinal Diseases/epidemiology/etiology ; Humans ; Incidence ; Influenza, Human/complications/epidemiology ; Male ; Mental Disorders/epidemiology/etiology ; Middle Aged ; Pain/epidemiology/etiology ; Proportional Hazards Models ; Retrospective Studies ; SARS-CoV-2 ; Severity of Illness Index ; *Survivors ; United States/epidemiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.}, } @article {pmid34580069, year = {2021}, author = {Michelen, M and Manoharan, L and Elkheir, N and Cheng, V and Dagens, A and Hastie, C and O'Hara, M and Suett, J and Dahmash, D and Bugaeva, P and Rigby, I and Munblit, D and Harriss, E and Burls, A and Foote, C and Scott, J and Carson, G and Olliaro, P and Sigfrid, L and Stavropoulou, C}, title = {Characterising long COVID: a living systematic review.}, journal = {BMJ global health}, volume = {6}, number = {9}, pages = {}, pmid = {34580069}, issn = {2059-7908}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prospective Studies ; *Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.

METHODS: A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.

RESULTS: A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case-control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.

CONCLUSION: Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.

PROSPERO REGISTRATION NUMBER: CRD42020211131.}, } @article {pmid34579171, year = {2021}, author = {Cereda, E and Clavé, P and Collins, PF and Holdoway, A and Wischmeyer, PE}, title = {Recovery Focused Nutritional Therapy across the Continuum of Care: Learning from COVID-19.}, journal = {Nutrients}, volume = {13}, number = {9}, pages = {}, pmid = {34579171}, issn = {2072-6643}, mesh = {COVID-19/complications/*therapy ; Continuity of Patient Care ; Health Personnel ; Humans ; Malnutrition/prevention & control ; *Nutrition Therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {Targeted nutritional therapy should be started early in severe illness and sustained through to recovery if clinical and patient-centred outcomes are to be optimised. The coronavirus disease 2019 (COVID-19) pandemic has shone a light on this need. The literature on nutrition and COVID-19 mainly focuses on the importance of nutrition to preserve life and prevent clinical deterioration during the acute phase of illness. However, there is a lack of information guiding practice across the whole patient journey (e.g., hospital to home) with a focus on targeting recovery (e.g., long COVID). This review paper is of relevance to doctors and other healthcare professionals in acute care and primary care worldwide, since it addresses early, multi-modal individualised nutrition interventions across the continuum of care to improve COVID-19 patient outcomes. It is of relevance to nutrition experts and non-nutrition experts and can be used to promote inter-professional and inter-organisational knowledge transfer on the topic. The primary goal is to prevent complications and support recovery to enable COVID-19 patients to achieve the best possible nutritional, physical, functional and mental health status and to apply the learning to date from the COVID-19 pandemic to other patient groups experiencing acute severe illness.}, } @article {pmid34575615, year = {2021}, author = {Boutou, AK and Asimakos, A and Kortianou, E and Vogiatzis, I and Tzouvelekis, A}, title = {Long COVID-19 Pulmonary Sequelae and Management Considerations.}, journal = {Journal of personalized medicine}, volume = {11}, number = {9}, pages = {}, pmid = {34575615}, issn = {2075-4426}, abstract = {The human coronavirus 2019 disease (COVID-19) and the associated acute respiratory distress syndrome (ARDS) are responsible for the worst global health crisis of the last century. Similarly, to previous coronaviruses leading to past pandemics, including severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), a growing body of evidence support that a substantial minority of patients surviving the acute phase of the disease present with long-term sequelae lasting for up to 6 months following acute infection. The clinical spectrum of these manifestations is widespread across multiple organs and consists of the long-COVID-19 syndrome. The aim of the current review is to summarize the current state of knowledge on the pulmonary manifestations of the long COVID-19 syndrome including clinical symptoms, parenchymal, and functional abnormalities, as well as highlight epidemiology, risk factors, and follow-up strategies for early identification and timely therapeutic interventions. The literature data on management considerations including the role of corticosteroids and antifibrotic treatment, as well as the therapeutic potential of a structured and personalized pulmonary rehabilitation program are detailed and discussed.}, } @article {pmid34575251, year = {2021}, author = {Vimercati, L and De Maria, L and Quarato, M and Caputi, A and Gesualdo, L and Migliore, G and Cavone, D and Sponselli, S and Pipoli, A and Inchingolo, F and Scarano, A and Lorusso, F and Stefanizzi, P and Tafuri, S}, title = {Association between Long COVID and Overweight/Obesity.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, pmid = {34575251}, issn = {2077-0383}, abstract = {BACKGROUND: Long COVID is a syndrome characterized by the persistence of SARS-CoV-2 infection symptoms. Among HCWs, prolonged COVID symptoms could lead to the inability to perform work tasks. The aim of this study is to investigate 35-day long-COVID (35-LC) characteristics and risk factors in a one-year period.

METHODS: We carried out a retrospective cohort study during the COVID-19 pandemic at University Hospital of Bari. A total of 5750 HCWs were tested for close contact with a confirmed case, in the absence of personal protective equipment, or for symptom development.

RESULTS: Each positive HCW was investigated for cardiovascular risk factors or respiratory diseases. An amount of 352 HCWs (6.1%) were infected by SARS-CoV-2, and 168 cases evolved to long COVID. The 35-LC group showed mean BMI values higher than the non-35-LC group (25.9 kg/m[2] vs. 24.8 kg/m[2], respectively), and this difference was significant (p-value: 0.020). Moreover, HCWs who suffered from pulmonary disease (OR = 3.7, CL 95%: 1.35-10.53; p-value = 0.007) or overweight (OR = 1.6 CL 95%: 1.05-2.56; p-value = 0.029) had an increased risk of developing 35-LC.

CONCLUSIONS: Long COVID is an emerging problem for hospital managers as it may reduce the number of HCWs deployed in the fight against COVID-19. High BMI and previous pulmonary disease could be risk factors for 35-LC development in exposed HCWs.}, } @article {pmid34575040, year = {2021}, author = {Hassan, EB and Phu, S and Warburton, E and Humaith, N and Wijeratne, T}, title = {Frailty in Stroke-A Narrated Review.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {34575040}, issn = {2075-1729}, abstract = {This narrative review provides a summary introduction to the relationship between stroke and physical and cognitive frailty syndromes and the neuro-inflammatory similarities (including inflammaging) between the two. The review argues the potential effects of Post COVID-19 Neurological Syndrome (PCNS, also known as Long COVID) with similar pathophysiology. Many patients who have suffered from acute stroke experience long-lasting symptoms affecting several organs including fatigue, brain fog, reduced physical activity, loss of energy, and loss of cognitive reserve, culminating in the loss of independence and poor quality of life. This is very similar to the emerging reports of PCNS from different parts of the world. Stroke, particularly in older adults with comorbidities appears to impact the health and welfare of patients by reducing central neuronal input and neuromuscular function, with muscular atrophy and neuropsychiatric complications. The cumulative effects can potentially lead to a range of physical and cognitive frailty syndromes, which, in many cases may be attributed to persistent, maladapted, low grade, chronic inflammation. Meanwhile, post-COVID-19 Neurological Syndrome (also known as Long COVID Syndrome) appears to share a similar trajectory, adding further urgency for investigations into the mechanisms underlying this constellation of symptoms.}, } @article {pmid34572201, year = {2021}, author = {Parisi, GF and Diaferio, L and Brindisi, G and Indolfi, C and Umano, GR and Klain, A and Marchese, G and Ghiglioni, DG and Zicari, AM and Marseglia, GL and Miraglia Del Giudice, M}, title = {Cross-Sectional Survey on Long Term Sequelae of Pediatric COVID-19 among Italian Pediatricians.}, journal = {Children (Basel, Switzerland)}, volume = {8}, number = {9}, pages = {}, pmid = {34572201}, issn = {2227-9067}, abstract = {The persistence of symptoms after recovery from Coronavirus 2019 (COVID-19) is defined as long COVID, an entity that had occurred among adults but which is not yet well characterized in pediatric ages. The purpose of this work was to present some of the data from a survey addressed to Italian pediatricians concerning the impact of long-COVID among children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The questionnaire was designed and pre-tested in February 2021 by a working group of experts from the Italian Pediatric Society for Allergy and Immunology (SIAIP). The survey was emailed once in March 2021 to a sample of Italian pediatricians. A total 267 Italian pediatricians participated in our survey. According to most pediatricians (97.3%), the persistence of symptoms is found in less than 20% of children. Specifically, with regard to the symptoms that persist even after swab negativization, fatigue was the most mentioned one (75.6%). Long-COVID would seem to be a phenomenon of limited occurrence in pediatric ages, affecting less than 20% of children. Among all of the symptoms, the one that was most prevalent was fatigue, a pathological entity that is associated with many viral diseases.}, } @article {pmid34569681, year = {2022}, author = {Méndez, R and Balanzá-Martínez, V and Luperdi, SC and Estrada, I and Latorre, A and González-Jiménez, P and Bouzas, L and Yépez, K and Ferrando, A and Reyes, S and Menéndez, R}, title = {Long-term neuropsychiatric outcomes in COVID-19 survivors: A 1-year longitudinal study.}, journal = {Journal of internal medicine}, volume = {291}, number = {2}, pages = {247-251}, pmid = {34569681}, issn = {1365-2796}, mesh = {*COVID-19/psychology ; Humans ; Longitudinal Studies ; Quality of Life ; *Survivors ; }, } @article {pmid34565368, year = {2021}, author = {Estiri, H and Strasser, ZH and Brat, GA and Semenov, YR and , and Patel, CJ and Murphy, SN}, title = {Evolving phenotypes of non-hospitalized patients that indicate long COVID.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {249}, pmid = {34565368}, issn = {1741-7015}, support = {FS/19/52/34563/BHF_/British Heart Foundation/United Kingdom ; R01 NS098023/NS/NINDS NIH HHS/United States ; 3U01HG008685-05S2/HG/NHGRI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; K23 HL148394/HL/NHLBI NIH HHS/United States ; L40 HL148910/HL/NHLBI NIH HHS/United States ; U01 HG008685/HG/NHGRI NIH HHS/United States ; MC_PC_18034/MRC_/Medical Research Council/United Kingdom ; T15 LM007092/LM/NLM NIH HHS/United States ; RF1 AG074372/AG/NIA NIH HHS/United States ; T32 LM012203/LM/NLM NIH HHS/United States ; }, mesh = {*COVID-19/complications/diagnosis ; Humans ; Phenotype ; Retrospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.

METHODS: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.

RESULTS: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients' medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.

CONCLUSIONS: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.}, } @article {pmid34565332, year = {2021}, author = {Begemann, M and Gross, O and Wincewicz, D and Hardeland, R and Daguano Gastaldi, V and Vieta, E and Weissenborn, K and Miskowiak, KW and Moerer, O and Ehrenreich, H}, title = {Addressing the 'hypoxia paradox' in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {27}, number = {1}, pages = {120}, pmid = {34565332}, issn = {1528-3658}, support = {TRR 274/1 2020 - 408885537//dfg/ ; R215-2015-4121//lundbeckfonden/ ; }, mesh = {COVID-19/*complications/genetics/pathology/virology ; Erythropoietin/analogs & derivatives/*genetics/therapeutic use ; Humans ; Hypoxia/*drug therapy/genetics/pathology/virology ; Lung/*drug effects/pathology/virology ; Pandemics ; Recombinant Proteins/genetics/therapeutic use ; SARS-CoV-2/drug effects ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called 'long COVID' and 'neuroCOVID', becomes increasingly evident. Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term 'hypoxia paradox'. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this 'hypoxia paradox' caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues.

SHORT CONCLUSION: Substitution of EPO may-among other beneficial EPO effects in severe COVID-19-circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.}, } @article {pmid34563706, year = {2021}, author = {Weinstock, LB and Brook, JB and Walters, AS and Goris, A and Afrin, LB and Molderings, GJ}, title = {Mast cell activation symptoms are prevalent in Long-COVID.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {112}, number = {}, pages = {217-226}, pmid = {34563706}, issn = {1878-3511}, mesh = {Adult ; *COVID-19/complications ; Female ; Humans ; Male ; *Mast Cell Activation Syndrome ; Mast Cells ; Middle Aged ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long-COVID (LC) symptoms. We determined prevalence/severity of MCA symptoms in LC.

METHODS: Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19. Questions included presence and severity of known MCA and LC symptoms and validated assessments of fatigue and quality of life. General population controls and mast cell activation syndrome (MCAS) patients were recruited for comparison if they were ≥18 years of age and never had overt COVID-19 symptoms.

RESULTS: There were 136 LC subjects (89.7% females, age 46.9 ±12.9 years), 136 controls (65.4% females, age 49.2 ±15.5), and 80 MCAS patients (85.0% females, age 47.7 ±16.4). Pre-COVID-19 LC subjects and controls had virtually identical MCA symptom and severity analysis. Post-COVID-19 LC subjects and MCAS patients prior to treatment had virtually identical MCA symptom and severity analysis.

CONCLUSIONS: MCA symptoms were increased in LC and mimicked the symptoms and severity reported by patients who have MCAS. Increased activation of aberrant mast cells induced by SARS-CoV-2 infection by various mechanisms may underlie part of the pathophysiology of LC, possibly suggesting routes to effective therapy.}, } @article {pmid34563621, year = {2022}, author = {Byrne, EA}, title = {Understanding Long Covid: Nosology, social attitudes and stigma.}, journal = {Brain, behavior, and immunity}, volume = {99}, number = {}, pages = {17-24}, doi = {10.1016/j.bbi.2021.09.012}, pmid = {34563621}, issn = {1090-2139}, mesh = {Attitude ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Social Stigma ; Post-Acute COVID-19 Syndrome ; }, abstract = {The debate around Long Covid has so far shown resistance to accept parallels between Long Covid and a set of existing conditions which have historically been subject to stigma. This resistance risks endorsing the stigma associated with such existing conditions, and as such, these dynamics of stigma ought to be dismantled in order to facilitate the development of effective clinical resources for all such implicated conditions. As well as affecting proceedings at the structural level, I discuss how the aforementioned problems also risk affecting patients at the personal level by motivating the reconfiguration and restriction of patient illness narratives. The problems I identify therefore risk affecting both collective and individual understanding of Long Covid.}, } @article {pmid34560321, year = {2021}, author = {Zuo, T and Wu, X and Wen, W and Lan, P}, title = {Gut Microbiome Alterations in COVID-19.}, journal = {Genomics, proteomics & bioinformatics}, volume = {19}, number = {5}, pages = {679-688}, pmid = {34560321}, issn = {2210-3244}, mesh = {Bacteria ; *COVID-19/complications ; Fungi ; *Gastrointestinal Microbiome ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.}, } @article {pmid34559820, year = {2021}, author = {Burges Watson, DL and Campbell, M and Hopkins, C and Smith, B and Kelly, C and Deary, V}, title = {Altered smell and taste: Anosmia, parosmia and the impact of long Covid-19.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0256998}, pmid = {34559820}, issn = {1932-6203}, mesh = {Adult ; *Anosmia/etiology/physiopathology/psychology ; *COVID-19/complications/physiopathology/psychology ; Female ; Humans ; Male ; Middle Aged ; *Olfactory Perception ; *SARS-CoV-2 ; *Taste Disorders/etiology/physiopathology/psychology ; *Taste Perception ; Time Factors ; }, abstract = {BACKGROUND: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell.

METHODS: We conducted exploratory thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020.

RESULTS: Participants reported difficulty explaining and managing an altered sense of taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others.

CONCLUSIONS: Our findings suggest altered taste and smell with Covid-19 may lead to severe disruption to daily living that impacts on psychological well-being, physical health, relationships and sense of self. More specifically, participants reported impacts that related to reduced desire and ability to eat and prepare food; weight gain, weight loss and nutritional insufficiency; emotional wellbeing; professional practice; intimacy and social bonding; and the disruption of people's sense of reality and themselves. Our findings should inform further research and suggest areas for the training, assessment and treatment practices of health care professionals working with long Covid.}, } @article {pmid34559059, year = {2021}, author = {Widmann, CN and Wieberneit, M and Bieler, L and Bernsen, S and Gräfenkämper, R and Brosseron, F and Schmeel, C and Tacik, P and Skowasch, D and Radbruch, A and Heneka, MT}, title = {Longitudinal Neurocognitive and Pulmonological Profile of Long COVID-19: Protocol for the COVIMMUNE-Clin Study.}, journal = {JMIR research protocols}, volume = {10}, number = {11}, pages = {e30259}, pmid = {34559059}, issn = {1929-0748}, abstract = {BACKGROUND: There is a dearth of information about "brain fog," characterized by concentration, word-finding, or memory problems, which has been listed in the new World Health Organization provisional classification "U09.9 Post-COVID-19 Condition." Moreover, the extent to which these symptoms may be associated with neurological, pulmonary, or psychiatric difficulties is unclear.

OBJECTIVE: This ongoing cohort study aims to carefully assess neurocognitive function in the context of the neurological, psychiatric, and pulmonary sequelae of SARS-CoV-2 infection among patients with asymptomatic/mild and severe cases of COVID-19 after remission, including actively recruited healthy controls.

METHODS: A total of 150 participants will be included in this pilot study. The cohort will comprise patients who tested positive for SARS-CoV-2 infection with either an asymptomatic course or a mild course defined as no symptoms except for olfactory and taste dysfunction (n=50), patients who tested positive for SARS-CoV-2 infection with a severe disease course (n=50), and a healthy control group (n=50) with similar age and sex distribution based on frequency matching. A comprehensive neuropsychological assessment will be performed comprising nuanced aspects of complex attention, including language, executive function, verbal and visual learning, and memory. Psychiatric, personality, social and lifestyle factors, sleep, and fatigue will be evaluated. Brain magnetic resonance imaging, neurological and physical assessment, and pulmonological and lung function examinations (including body plethysmography, diffusion capacity, clinical assessments, and questionnaires) will also be performed. Three visits are planned with comprehensive testing at the baseline and 12-month visits, along with brief neurological and neuropsychological examinations at the 6-month assessment. Blood-based biomarkers of neurodegeneration will be quantified at baseline and 12-month follow-up.

RESULTS: At the time of submission, the study had begun recruitment through telephone and in-person screenings. The first patient was enrolled in the study at the beginning of April 2021. Interim data analysis of baseline information is expected to be complete by December 2021 and study completion is expected at the end of December 2022. Preliminary group comparisons indicate worse word list learning, short- and long-delayed verbal recall, and verbal recognition in both patient cohorts compared with those of the healthy control group, adjusted for age and sex. Initial volumetric comparisons show smaller grey matter, frontal, and temporal brain volumes in both patient groups compared with those of healthy controls. These results are quite robust but are neither final nor placed in the needed context intended at study completion.

CONCLUSIONS: To the best of our knowledge, this is the first study to include objective and comprehensive longitudinal analyses of neurocognitive sequelae of COVID-19 in an extreme group comparison stratified by disease severity with healthy controls actively recruited during the pandemic. Results from this study will contribute to the nascent literature on the prolonged effects of COVID-19 on neurocognitive performance via our coassessment of neuroradiological, neurological, pulmonary, psychiatric, and lifestyle factors.

TRIAL REGISTRATION: International Clinical Trials Registry Platform DRKS00023806; https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00023806.

DERR1-10.2196/30259.}, } @article {pmid34558550, year = {2021}, author = {Chu, M and Gopikrishna, D and Rocke, J and Kumar, BN}, title = {Implementing a COVID-19 specialist smell clinic: experience at the Wrightington, Wigan and Leigh Teaching Hospitals (WWL), NHS Foundation Trust, United Kingdom.}, journal = {The Medical journal of Malaysia}, volume = {76}, number = {Suppl 4}, pages = {9-13}, pmid = {34558550}, issn = {0300-5283}, mesh = {Adult ; Anosmia/diagnosis/*virology ; *COVID-19/complications ; Female ; Hospitals, Teaching ; Humans ; Male ; Quality of Life ; *Smell ; State Medicine ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: It is clear that a proportion of patients continue to suffer long-lasting symptoms following acute infection with coronavirus disease 2019 (COVID-19). Persistent olfactory dysfunction is one of the commonest complaints reported in the condition colloquially known as long COVID (now known as post-acute sequelae of SARS-CoV-2 infection (PASC)). The prevalence, risk factors and clinical course of long COVID olfactory dysfunction are not yet well understood. At present, the main stay of treatment is olfactory training. Quantitative olfactory testing and impacts on patient quality of life have not been widely studied. This study describes our experiences at Wrightington, Wigan and Leigh Teaching Hospitals, UK (WWL) of establishing a COVID-19 smell clinic, along with preliminary data on patient demographics, baseline smell test scores and quality of life questionnaire scores before olfactory training.

METHODS: We piloted a COVID-19 smell clinic. We recorded patient demographics and clinical characteristics then performed clinical assessment of each patient. Quantitative measurements of olfactory dysfunction were recorded using the University of Pennsylvania Smell Identification Test (UPSIT). We measured the impact of olfactory dysfunction on patient quality of life using the validated English Olfactory Disorders Questionnaire (eODQ).

RESULTS: 20 patients participated in the clinic. 4 patients were excluded from analysis due to missing data. Median age was 35 years. 81% (n=13) of the participants were female. 50% (n=8) of patients suffered with a combination of anosmia/ageusia and parosmia, whilst 43% (n=7) of patients suffered with anosmia/ageusia without parosmia. Almost all the patients registered UPSIT scores in keeping with impaired olfaction. Patient scores ranged from 22 to 35, with the median score at 30. All patients reported that their olfactory dysfunction had an impact on their quality of life. The median eODQ score reported was 90, with scores ranging from 42 to 169 out of a maximum of 180.

CONCLUSION: We have demonstrated that it is simple and feasible to set up a COVID-19 smell clinic. The materials are inexpensive, but supervised completion of the UPSIT and eODQ is time-consuming. Patients demonstrate reduced olfaction on quantitative testing and experience significant impacts on their quality of life as a result. More research is needed to demonstrate if olfactory training results in measurable improvements in smell test scores and quality of life.}, } @article {pmid34556492, year = {2021}, author = {Wild, JM and Porter, JC and Molyneaux, PL and George, PM and Stewart, I and Allen, RJ and Aul, R and Baillie, JK and Barratt, SL and Beirne, P and Bianchi, SM and Blaikley, JF and Brooke, J and Chaudhuri, N and Collier, G and Denneny, EK and Docherty, A and Fabbri, L and Gibbons, MA and Gleeson, FV and Gooptu, B and Hall, IP and Hanley, NA and Heightman, M and Hillman, TE and Johnson, SR and Jones, MG and Khan, F and Lawson, R and Mehta, P and Mitchell, JA and Platé, M and Poinasamy, K and Quint, JK and Rivera-Ortega, P and Semple, M and Simpson, AJ and Smith, D and Spears, M and Spencer, LG and Stanel, SC and Thickett, DR and Thompson, AAR and Walsh, SL and Weatherley, ND and Weeks, ME and Wootton, DG and Brightling, CE and Chambers, RC and Ho, LP and Jacob, J and Piper Hanley, K and Wain, LV and Jenkins, RG}, title = {Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).}, journal = {BMJ open respiratory research}, volume = {8}, number = {1}, pages = {}, pmid = {34556492}, issn = {2052-4439}, support = {MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MR/W006111/1/MRC_/Medical Research Council/United Kingdom ; G1000861/MRC_/Medical Research Council/United Kingdom ; SP/14/6/31350/BHF_/British Heart Foundation/United Kingdom ; MC_PC_20022/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; FS/18/13/33281/BHF_/British Heart Foundation/United Kingdom ; MR/M008894/1/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; MR/T032529/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications ; Humans ; Longitudinal Studies ; *Lung Diseases, Interstitial/epidemiology ; Observational Studies as Topic ; Pandemics ; Prospective Studies ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).

METHODS AND ANALYSIS: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.

ETHICS AND DISSEMINATION: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.

CONCLUSION: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.}, } @article {pmid34554794, year = {2021}, author = {Kaiser, J}, title = {Large study will probe Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6562}, pages = {1429}, doi = {10.1126/science.acx9162}, pmid = {34554794}, issn = {1095-9203}, mesh = {*Biomedical Research ; COVID-19/*complications ; Humans ; National Institutes of Health (U.S.) ; Patient Selection ; Research Support as Topic ; United States ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34554270, year = {2021}, author = {Thurnher, MM and Reith, W and Thurnher, AP and Rommer, P}, title = {[Long COVID: long-term symptoms and morphological/radiological correlates].}, journal = {Der Radiologe}, volume = {61}, number = {10}, pages = {915-922}, pmid = {34554270}, issn = {1432-2102}, mesh = {Adult ; *COVID-19/complications ; Disease Progression ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Neurologic, pulmonary, cardiac and gastrointestinal functional disorders can persist in the post-acute phase and constitute a long COVID syndrome, also known as post-acute sequelae of SARS-CoV‑2 infection (PASC). Some patients develop persistent and debilitating symptoms despite a relatively mild illness at onset and they are known as COVID-19 long haulers.

OBJECTIVE: Presentation of symptoms, signs and biomarkers present in patients previously affected by COVID-19 and discussion of possible underlying mechanisms and consequences.

METHODS: Existing literature and reported cases as well as expert opinions are analyzed and discussed.

RESULTS: Long COVID affects survivors of COVID-19 at all levels of disease severity, even in mild to moderate cases and younger adults who did not require respiratory support, hospitalization or intensive care. A challenging aspect is that many long haulers never had laboratory confirmation of COVID-19, raising skepticism that the persistent symptoms have a physiological basis. On the other hand, some symptoms seen in post-acute COVID-19 may occur as a consequence of critical illness or as a side effect of treatment.

CONCLUSION: Given that COVID-19 is a new disease, it is not possible to determine how long these effects will last. Long-term monitoring of post-acute COVID-19 symptoms and screening for frequent comorbid conditions are essential.}, } @article {pmid34551971, year = {2021}, author = {Brown, DA and O'Brien, KK}, title = {Conceptualising Long COVID as an episodic health condition.}, journal = {BMJ global health}, volume = {6}, number = {9}, pages = {}, pmid = {34551971}, issn = {2059-7908}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34551007, year = {2021}, author = {Ares-Blanco, S and Pérez Álvarez, M and Gefaell Larrondo, I and Muñoz, C and Aguilar Ruiz, V and Castelo Jurado, M and Guisado-Clavero, M}, title = {SARS-CoV-2 pneumonia follow-up and long COVID in primary care: A retrospective observational study in Madrid city.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257604}, pmid = {34551007}, issn = {1932-6203}, mesh = {Humans ; *COVID-19/epidemiology/complications ; Spain/epidemiology ; Male ; Female ; Retrospective Studies ; *Primary Health Care/statistics & numerical data ; Middle Aged ; Aged ; *SARS-CoV-2/isolation & purification ; Follow-Up Studies ; Adult ; Pneumonia, Viral/epidemiology/complications/diagnosis ; Pandemics ; Hospitalization/statistics & numerical data ; Cough/epidemiology ; Coronavirus Infections/epidemiology/diagnosis/complications ; Betacoronavirus/isolation & purification ; Aged, 80 and over ; }, abstract = {BACKGROUND: Patients with COVID-19 are follow-up in primary care and long COVID is scarcely defined. The study aim was to describe SARS-CoV-2 pneumonia and cut-offs for defining long COVID in primary care follow-up patients.

METHODS: A retrospective observational study in primary care in Madrid, Spain, was conducted. Data was collected during 6 months (April to September) in 2020, during COVID-19 first wave, from patients ≥ 18 years with SARS-CoV-2 pneumonia diagnosed. Variables: sociodemographic, comorbidities, COVID-19 symptoms and complications, laboratory test and chest X-ray. Descriptive statistics were used, mean (standard deviation (SD)) and medians (interquartile range (IQR)) respectively. Differences were detected applying X2 test, Student's T-test, ANOVA, Wilcoxon-Mann-Whitney or Kruskal-Wallis depending on variable characteristics.

RESULTS: 155 patients presented pneumonia in day 7.8 from the onset (79.4% were hospitalized, median length of 7.0 days (IQR: 3.0, 13.0)). After discharge, the follow-up lasted 54.0 median days (IQR 42.0, 88.0) and 12.2 mean (SD 6.4) phone calls were registered per patient. The main symptoms and their duration were: cough (41.9%, 12 days), dyspnoea (31.0%, 15 days), asthenia (26.5%, 21 days). Different cut-off points were applied for long COVID and week 4 was considered the best milestone (28.3% of the sample still had symptoms after week 4) versus week 12 (8.3%). Patients who still had symptoms >4 weeks follow-up took place over 81.0 days (IQR: 50.5, 103.0), their symptoms were more prevalent and lasted longer than those ≤ 4 weeks: cough (63.6% 30 days), dyspnoea (54.6%, 46 days), and asthenia (56.8%, 29 days). Embolism was more frequent in patients who still had symptoms >4 weeks than those with symptoms ≤4 weeks (9.1% vs 1.8%, p value 0.034).

CONCLUSION: Most patients with SARS-CoV-2 pneumonia recovered during the first 4 weeks from the beginning of the infection. The cut-off point to define long COVID, as persisting symptoms, should be between 4 to 12 weeks from the onset of the symptoms.}, } @article {pmid34549296, year = {2021}, author = {Szarpak, L and Jaguszewski, MJ and Pruc, M and Rafique, Z}, title = {Myocardial injury: a future challenge for long-COVID-19 complications.}, journal = {European heart journal. Quality of care & clinical outcomes}, volume = {7}, number = {6}, pages = {618}, doi = {10.1093/ehjqcco/qcab067}, pmid = {34549296}, issn = {2058-1742}, mesh = {*COVID-19/complications ; *Heart Injuries ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34549199, year = {2021}, author = {Lamontagne, SJ and Winters, MF and Pizzagalli, DA and Olmstead, MC}, title = {Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment.}, journal = {Brain, behavior, & immunity - health}, volume = {17}, number = {}, pages = {100347}, pmid = {34549199}, issn = {2666-3546}, support = {R01 MH095809/MH/NIMH NIH HHS/United States ; R37 MH068376/MH/NIMH NIH HHS/United States ; }, abstract = {Acute health consequences associated with coronavirus disease 2019 (COVID-19) infection have been thoroughly characterized; however, long-term impacts are not yet understood. Post-acute sequelae of COVID-19 (PASC), also known as Long COVID syndrome, is the persistence of COVID-19 symptoms long after viral infection. In addition to physical symptoms, those with PASC experience changes in mental health, but few studies have empirically examined these effects. The current study investigated mood and cognitive functioning in individuals who have recovered from COVID-19 infection. We recruited 100 male and female adults (M = 30 years old) with no history of mood or cognitive impairment prior to the COVID-19 pandemic (Jan. 2020). Half of the subjects were healthy controls (i.e., no prior COVID-19 infection) and half had received a past COVID-19 diagnosis (ascertained by PCR or antibody test) but were no longer infectious. Participants completed self-reported measures of stress, depression, and anhedonia, as well as the Attention Network Test (ANT), a behavioural measure of attentional alerting, orienting and executive functioning. Relative to controls, depression and anhedonia were significantly higher in the past-COVID group. Selective impairment in attention was observed in the past-COVID group, marked by deficits in executive functioning while alerting and orienting abilities remained intact. Effects were most pronounced among individuals diagnosed 1-4 months prior to assessment. There were no group differences in pandemic-related experiences with respect to social interaction, social distancing, or isolation. The past-COVID group scored significantly higher on perceived stress; however, this did not moderate any effects observed on mood or cognition. These findings implicate a protracted reaction to the virus, possibly via prolonged inflammation, contributing to sustained mood dysregulation and cognitive impairment. Future research should examine the neural and physiological underpinnings of PASC, particularly mechanisms that promote psychiatric sequelae 1-4 months following diagnosis.}, } @article {pmid34547487, year = {2021}, author = {Colaneri, M and De Filippo, M and Licari, A and Marseglia, A and Maiocchi, L and Ricciardi, A and Corsico, A and Marseglia, G and Mondelli, MU and Bruno, R}, title = {COVID vaccination and asthma exacerbation: might there be a link?.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {112}, number = {}, pages = {243-246}, pmid = {34547487}, issn = {1878-3511}, mesh = {Adolescent ; Adult ; *Asthma ; *COVID-19 ; COVID-19 Vaccines ; Child ; Female ; Humans ; SARS-CoV-2 ; Vaccination ; }, abstract = {INTRODUCTION: There is ongoing debate regarding the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of coronavirus disease 2019 (COVID-19) vaccination on asthma is entirely unexplored.

CASE STUDY: This study examined a challenging case of severe asthma exacerbation in a 28-year-old female following two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at IRCCS Policlinico San Matteo in Pavia, Italy. The patient, a fourth-year resident at the hospital, was vaccinated in early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She tested negative for SARS-CoV-2 on several molecular swabs and serology tests.

RESULTS: After receiving the second dose of vaccine, the patient started to experience worsening of respiratory symptoms. Following several episodes and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug (interleukin-5) antagonist monoclonal antibody.

CONCLUSION: This single case study is insufficient to draw conclusions about the association between asthma exacerbation and the COVID-19 vaccine. While the cause-effect link between vaccination against SARS-CoV-2 and worsening of asthmatic disease might only be suggested at present, this case is a valuable prompt for further investigation. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe.}, } @article {pmid34541421, year = {2021}, author = {Jiang, DH and Roy, DJ and Gu, BJ and Hassett, LC and McCoy, RG}, title = {Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review.}, journal = {JACC. Basic to translational science}, volume = {6}, number = {9}, pages = {796-811}, pmid = {34541421}, issn = {2452-302X}, abstract = {The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations. Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.}, } @article {pmid34539470, year = {2021}, author = {Gouraud, C and Bottemanne, H and Lahlou-Laforêt, K and Blanchard, A and Günther, S and Batti, SE and Auclin, E and Limosin, F and Hulot, JS and Lebeaux, D and Lemogne, C}, title = {Association Between Psychological Distress, Cognitive Complaints, and Neuropsychological Status After a Severe COVID-19 Episode: A Cross-Sectional Study.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {725861}, pmid = {34539470}, issn = {1664-0640}, abstract = {Background: Cognitive complaints are frequent after COVID-19 but their clinical determinants are poorly understood. This study aimed to explore the associations of objective cognitive performances and psychological distress with cognitive complaints in COVID-19 survivors. Materials and Methods: Patients previously hospitalized for COVID-19 in a university hospital during the first wave of COVID-19 pandemic in France were followed-up at 1 month after their admission. Cognitive complaints were self-reported and standardized instruments were used to assess neuropsychological status (Digit Symbol Substitution Test, Semantic Verbal Fluency Test, Mini Mental Status Examination) and psychological distress (Hospital Anxiety and Depression Scale, HADS). Multivariable analyses were adjusted for age, sex, admission in intensive care unit (ICU) and need for oxygen and C-reactive protein. Results: One hundred patients (34% women, median age: 60 years [interquartile range: 49-72)] completed the neuropsychological assessment at follow-up. In multivariable analyses, cognitive complaints at 1-month were associated with greater HADS score (OR for one interquartile range: OR: 1.96, 95% CI: 1.08-3.57) and older age (OR: 1.05, 95% CI: 1.01-1.09) and, negatively, with admission in ICU (OR: 0.22, 95% CI: 0.05-0.90). In contrast, none of the objective neuropsychological test scores was significantly associated with cognitive complaints. Exploratory analysis showed that cognitive complaints were associated with both anxiety and depressive symptoms. Discussion: These preliminary results suggest that cognitive complaints at 1 month after a hospitalization for COVID-19 are associated with psychological distress, independently of objective neuropsychological status. Anxiety and depression symptoms should be systematically screened in patients presenting with cognitive complaints after a severe COVID-19 episode.}, } @article {pmid34537995, year = {2021}, author = {Aly, MAEG and Saber, HG}, title = {Long COVID and chronic fatigue syndrome: A survey of elderly female survivors in Egypt.}, journal = {International journal of clinical practice}, volume = {75}, number = {12}, pages = {e14886}, pmid = {34537995}, issn = {1742-1241}, mesh = {Aged ; *COVID-19/complications ; Cross-Sectional Studies ; Egypt ; *Fatigue Syndrome, Chronic/epidemiology/virology ; Female ; Humans ; Retrospective Studies ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: This study aimed to investigate post-COVID-19 symptoms amongst elderly females and whether they could be a risk factor for developing chronic fatigue syndrome (CFS) later on.

METHODS: This was a retrospective cross-sectional study, in the form of an online survey. A total of 115 responses were finally included.

RESULTS: The mean age was 73.18 ± 6.42. Eighty-nine reported symptoms in the post-recovery period; of these 54 had no symptoms of CFS, 60 were possible, and only 1 was probable. Fatigue was reported by 66, musculoskeletal symptoms by 56, and sleep problems by 73. Twenty-nine patients visited a doctor's office as a result. Post-recovery symptoms were significantly related to stress, sadness and sleep disturbances. Also, stress, sadness, sleep disturbances, fatigue, cognitive impairment, and recurrent falls were all significantly associated with CFS-like symptoms.

CONCLUSIONS: From our findings, the presence of fatigue, cognitive impairment, stress, sadness, sleep disturbances and recurrent falls in the post-recovery period were all significantly associated with CFS-like symptoms. To conclude it would be reasonable to screen for long COVID and consider the potential for developing CFS later on. Whether it can be a risk factor for developing CFS-like other viral infections will need more larger scale studies to confirm this.}, } @article {pmid34535526, year = {2021}, author = {Davin-Casalena, B and Lutaud, R and Scronias, D and Guagliardo, V and Verger, P}, title = {French General Practitioners Frequently See Patients with Long-COVID.}, journal = {Journal of the American Board of Family Medicine : JABFM}, volume = {34}, number = {5}, pages = {1010-1013}, doi = {10.3122/jabfm.2021.05.210142}, pmid = {34535526}, issn = {1558-7118}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; *General Practitioners ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {A second epidemic has appeared among some patients infected with COVID-19 persistent disorders, commonly called "long COVID syndrome." Our study sought to identify the proportion of French GPs dealing with patients with potential long COVID syndrome and their symptoms in an online cross-sectional questionnaire-based survey among a representative national panel of GPs. The majority (53.8%) reported at least 1 patient with COVID-19 and persistent symptoms, and 33% 2 or more such patients. Their most frequent symptoms were respiratory difficulties (60.6%), psychological distress (42.8%), and anosmia-dysgeusia (40.8%). Long COVID syndrome's recognition, management, and rehabilitation are priorities requiring effective coordination between primary and secondary care.}, } @article {pmid34533807, year = {2021}, author = {Ahmad, MS and Shaik, RA and Ahmad, RK and Yusuf, M and Khan, M and Almutairi, AB and Alghuyaythat, WKZ and Almutairi, SB}, title = {"LONG COVID": an insight.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {17}, pages = {5561-5577}, doi = {10.26355/eurrev_202109_26669}, pmid = {34533807}, issn = {2284-0729}, mesh = {COVID-19/*complications/epidemiology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the long-term effects on survivors. We thoroughly searched the databases for relevant articles till May 2021. The research articles that met our inclusion and exclusion criteria were assessed and reviewed by two independent researchers. After preliminary screening of the identified articles through title and abstract, 249 were selected. Consequently, 167 full-text articles were assessed and reviewed based on our inclusion criteria and thus 20 articles were regarded as eligible and analyzed in the present analysis. All the studies included adult population aged between 18 and above 60 years. The median length of hospital stay of the COVID-19 patients during the acute infection phase ranged from 8 days to 17 days. The most common prevalent long-term symptoms in COVID-19 patients included persistent fatigue and dyspnea in almost all of the studies. Other reported common symptoms included: shortness of breath, cough, joint pain, chest pain or tightness, headache, loss of smell/taste, sore throat, diarrhea, loss of memory, depression, anxiety. Associated cardiovascular events included arrhythmias, palpitations and hypotension, increased HR, venous thromboembolic diseases, myocarditis, and acute/decompensated heart failure as well. Among neurological manifestations headache, peripheral neuropathy symptoms, memory issues, concentration, and sleep disorders were most commonly observed with varying frequencies. Mental health issues affecting mental abilities, mood fluctuations namely anxiety and depression, and sleep disorders were commonly seen. Further, diarrhea, vomiting, digestive disorders, and Loss of appetite or weight loss are common gastrointestinal manifestations. Therefore, appropriate clinical evaluation is required in long COVID cases which in turn may help us to identify the risk factors, etiology, and to my help, we treat them early with appropriate management strategies.}, } @article {pmid34533706, year = {2021}, author = {Bleckwenn, M}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {16}, pages = {12-15}, doi = {10.1007/s15006-021-0231-y}, pmid = {34533706}, issn = {1613-3560}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34531277, year = {2022}, author = {Ortona, E and Malorni, W}, title = {Long COVID: to investigate immunological mechanisms and sex/gender related aspects as fundamental steps for tailored therapy.}, journal = {The European respiratory journal}, volume = {59}, number = {2}, pages = {}, pmid = {34531277}, issn = {1399-3003}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID was detected in both adults and children and is characterised by immunological dysregulation. Autoimmune reactions in adult patients and allergic reactions in children appear to be critical factors. https://bit.ly/38RfSyT}, } @article {pmid34531126, year = {2022}, author = {Espinosa Rodríguez, P and Martínez Aguilar, A and Ripoll Muñoz, MP and Rodríguez Navarro, MÁ}, title = {[Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations].}, journal = {Semergen}, volume = {48}, number = {1}, pages = {63-69}, pmid = {34531126}, issn = {1578-8865}, mesh = {*COVID-19/complications ; Consensus ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis. Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.}, } @article {pmid34529639, year = {2021}, author = {Yomogida, K and Zhu, S and Rubino, F and Figueroa, W and Balanji, N and Holman, E}, title = {Post-Acute Sequelae of SARS-CoV-2 Infection Among Adults Aged ≥18 Years - Long Beach, California, April 1-December 10, 2020.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {70}, number = {37}, pages = {1274-1277}, pmid = {34529639}, issn = {1545-861X}, mesh = {Adolescent ; Adult ; Aged ; COVID-19/*complications/epidemiology/therapy ; California/epidemiology ; Female ; *Health Status Disparities ; Humans ; Male ; Middle Aged ; Risk Factors ; Treatment Outcome ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-acute sequelae of COVID-19, also known as "long COVID," is used to describe the long-term symptoms that might be experienced weeks to months after primary infection with SARS-CoV-2, the virus that causes COVID-19. Among persons with a previous COVID-19 diagnosis, estimates of the prevalence of sequelae range from 5% among nonhospitalized persons to 80% among hospitalized persons (1,2). Studies have analyzed the aftereffects of COVID-19, but few have assessed the demographic characteristics associated with long COVID (3,4). Health disparities resulting from pervasive structural and socioeconomic barriers in the U.S. health care system might contribute to differences in these effects and might continue to exacerbate existing inequities (5). To identify trends in post-acute sequelae, the Long Beach Department of Health and Human Services (LBDHHS) interviewed a random sample of 366 persons aged ≥18 years who received a positive SARS-CoV-2 test result during April 1-December 10, 2020. One third of the persons interviewed reported having at least one symptom 2 months after their positive test result, with higher odds of sequelae among persons aged 40-54 years, females, and those with preexisting conditions. Black or African American (Black) participants had higher odds of reporting dyspnea and myalgia/arthralgia compared with other racial/ethnic groups. Persons who were aged ≥40 years, female, Black, or who reported known preexisting conditions also reported higher numbers of distinct sequelae. As the number of recovered COVID-19 patients increases, monitoring the prevalence of post-acute sequelae among larger cohorts in diverse populations will be necessary to understand and manage this condition. Identification of groups disproportionately affected by post-acute COVID-19 sequelae can help develop efforts to prioritize preventions and treatment strategies, including vaccination of groups at higher risk for these long-term sequelae, and access to testing and care for post-acute sequelae.}, } @article {pmid34529126, year = {2021}, author = {Milos, RI and Kifjak, D and Heidinger, BH and Prayer, F and Beer, L and Röhrich, S and Wassipaul, C and Gompelmann, D and Prosch, H}, title = {[Morphological and functional sequelae after COVID-19 pneumonia].}, journal = {Der Radiologe}, volume = {61}, number = {10}, pages = {888-895}, pmid = {34529126}, issn = {1432-2102}, mesh = {*COVID-19 ; Humans ; Lung/diagnostic imaging ; *Pneumonia ; Respiratory Function Tests ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment.

OBJECTIVES: To discuss the role of long-term assessment of COVID-19 patients to determine which patients may benefit from follow-up.

MATERIALS AND METHODS: This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia.

RESULTS: Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time.

CONCLUSIONS: Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a multidisciplinary manner.}, } @article {pmid34521686, year = {2021}, author = {Mahase, E}, title = {Covid-19: Long covid must be recognised as occupational disease, says BMA.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n2258}, doi = {10.1136/bmj.n2258}, pmid = {34521686}, issn = {1756-1833}, } @article {pmid34519974, year = {2022}, author = {Fernández-de-Las-Peñas, C}, title = {Long COVID: current definition.}, journal = {Infection}, volume = {50}, number = {1}, pages = {285-286}, pmid = {34519974}, issn = {1439-0973}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34517856, year = {2021}, author = {Deuel, JW and Schlagenhauf, P}, title = {In for the long-haul? Seropositivity and sequelae 1 year post COVID-19.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {200}, pmid = {34517856}, issn = {1741-7015}, mesh = {*COVID-19 ; Disease Progression ; Humans ; SARS-CoV-2 ; }, } @article {pmid34514834, year = {2021}, author = {Glasper, A}, title = {Strategies and policies to tackle the problems associated with long COVID.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {30}, number = {16}, pages = {984-985}, doi = {10.12968/bjon.2021.30.16.984}, pmid = {34514834}, issn = {2052-2819}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; Policy ; SARS-CoV-2 ; State Medicine ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, abstract = {Emeritus Professor Alan Glasper, from the University of Southampton, discusses strategies and polices designed to address rising levels of long COVID in society in the aftermath of the pandemic.}, } @article {pmid34514439, year = {2021}, author = {Baker, FL and Smith, KA and Zúñiga, TM and Batatinha, H and Niemiro, GM and Pedlar, CR and Burgess, SC and Katsanis, E and Simpson, RJ}, title = {Acute exercise increases immune responses to SARS CoV-2 in a previously infected man.}, journal = {Brain, behavior, & immunity - health}, volume = {18}, number = {}, pages = {100343}, pmid = {34514439}, issn = {2666-3546}, abstract = {Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease in patients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an adenovirus vector-based COVID-19 vaccine. Using whole blood SARS-CoV-2 peptide stimulation assays, IFN-γ ELISPOT assays, flow cytometry, ex vivo viral-specific T-cell expansion assays and deep T-cell receptor (TCR) β sequencing, we found that exercise robustly mobilized highly functional SARS-CoV-2 specific T-cells to the blood compartment that recognized spike protein, membrane protein, nucleocapsid antigen and the B.1.1.7 α-variant, and consisted mostly of CD3+/CD8+ T-cells and double-negative (CD4-/CD8-) CD3[+] T-cells. The magnitude of SARS-CoV-2 T-cell mobilization with exercise was intensity dependent and robust when compared to T-cells recognizing other viruses (e.g. CMV, EBV, influenza). Vaccination enhanced the number of exercise-mobilized SARS-CoV-2 T-cells recognizing spike protein and the α-variant only. Exercise-mobilized SARS-CoV-2 specific T-cells proliferated more vigorously to ex vivo peptide stimulation and maintained broad TCR-β diversity against SARS-CoV-2 antigens both before and after ex vivo expansion. Neutralizing antibodies to SARS-CoV-2 were transiently elevated during exercise after both infection and vaccination. Finally, infection was associated with an increased metabolic demand to defined exercise workloads, which was restored to pre-infection levels after vaccination. This case study provides impetus for larger studies to determine if these immune responses to exercise can facilitate viral clearance, ameliorate symptoms of long COVID syndrome, and/or restore functional exercise capacity following SARS-CoV-2 infection.}, } @article {pmid34512810, year = {2021}, author = {Mrusek, M}, title = {[Not Available].}, journal = {Pneumo news}, volume = {13}, number = {4}, pages = {53}, doi = {10.1007/s15033-021-2752-6}, pmid = {34512810}, issn = {2199-3866}, } @article {pmid34511734, year = {2021}, author = {Bär, C and Derda, AA and Thum, T}, title = {[Not Available].}, journal = {Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM)}, volume = {27}, number = {5}, pages = {485-487}, pmid = {34511734}, issn = {0947-0867}, abstract = {COVID-19 still remains a severe global health threat. Despite the high-speed development of vaccines that efficiently prevent COVID-19, there are still no effective treatments of the disease once people are infected. MicroRNAs are powerful regulators of gene expression. They are intensely investigated as therapeutic targets up to the clinical stage. In addition, microRNAs can be detected in the circulation, and thus, represent promising diagnostic and prognostic biomarkers for (long)-COVID-19.}, } @article {pmid34509649, year = {2021}, author = {Anaya, JM and Rojas, M and Salinas, ML and Rodríguez, Y and Roa, G and Lozano, M and Rodríguez-Jiménez, M and Montoya, N and Zapata, E and , and Monsalve, DM and Acosta-Ampudia, Y and Ramírez-Santana, C}, title = {Post-COVID syndrome. A case series and comprehensive review.}, journal = {Autoimmunity reviews}, volume = {20}, number = {11}, pages = {102947}, pmid = {34509649}, issn = {1873-0183}, mesh = {Adult ; *Antibodies, Viral ; *COVID-19 ; Female ; Humans ; Immunoglobulin G ; Lung ; Middle Aged ; SARS-CoV-2 ; }, abstract = {The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection and PCS were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8-55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143-258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2-1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.}, } @article {pmid34509350, year = {2021}, author = {Berenguera, A and Jacques-Aviñó, C and Medina-Perucha, L and Puente, D}, title = {Long term consequences of COVID-19.}, journal = {European journal of internal medicine}, volume = {92}, number = {}, pages = {34-35}, pmid = {34509350}, issn = {1879-0828}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, } @article {pmid34508837, year = {2021}, author = {Szekely, Y and Lichter, Y and Sadon, S and Lupu, L and Taieb, P and Banai, A and Sapir, O and Granot, Y and Hochstadt, A and Friedman, S and Laufer-Perl, M and Banai, S and Topilsky, Y}, title = {Cardiorespiratory Abnormalities in Patients Recovering from Coronavirus Disease 2019.}, journal = {Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography}, volume = {34}, number = {12}, pages = {1273-1284.e9}, pmid = {34508837}, issn = {1097-6795}, mesh = {*COVID-19 ; Exercise Test ; Exercise Tolerance ; *Heart Failure ; Humans ; Oxygen Consumption ; Oxygen Saturation ; SARS-CoV-2 ; Stroke Volume ; Ventricular Function, Left ; }, abstract = {BACKGROUND: A large number of patients around the world are recovering from coronavirus disease 2019 (COVID-19); many of them report persistence of symptoms. The aim of this study was to test pulmonary, cardiovascular, and peripheral responses to exercise in patients recovering from COVID-19.

METHODS: Patients who recovered from COVID-19 were prospectively evaluated using a combined anatomic and functional assessment. All patients underwent clinical examination, laboratory tests, and combined stress echocardiography and cardiopulmonary exercise testing. Left ventricular volumes, ejection fraction, stroke volume, heart rate, E/e' ratio, right ventricular function, oxygen consumption (Vo2), lung volumes, ventilatory efficiency, oxygen saturation, and muscle oxygen extraction were measured in all effort stages and compared with values in historical control subjects.

RESULTS: A total of 71 patients were assessed 90.6 ± 26 days after the onset of COVID-19 symptoms. Only 23 (33%) were asymptomatic. The most common symptoms were fatigue (34%), muscle weakness or pain (27%), and dyspnea (22%). Vo2 was lower among post-COVID-19 patients compared with control subjects (P = .03, group-by-time interaction P = .007). Reduction in peak Vo2 was due to a combination of chronotropic incompetence (75% of post-COVID-19 patients vs 8% of control subjects, P < .0001) and an insufficient increase in stroke volume during exercise (P = .0007, group-by-time interaction P = .03). Stroke volume limitation was mostly explained by diminished increase in left ventricular end-diastolic volume (P = .10, group-by-time interaction P = .03) and insufficient increase in ejection fraction (P = .01, group-by-time interaction P = .01). Post-COVID-19 patients had higher peripheral oxygen extraction (P = .004) and did not have significantly different respiratory and gas exchange parameters compared with control subjects.

CONCLUSIONS: Patients recovering from COVID-19 have symptoms associated with objective reduction in peak Vo2. The mechanism of this reduction is complex and mainly involves a combination of attenuated heart rate and stroke volume reserve.}, } @article {pmid34508486, year = {2021}, author = {Sundar Shrestha, D and Love, R}, title = {Long COVID Patient Symptoms and its Evaluation and Management.}, journal = {JNMA; journal of the Nepal Medical Association}, volume = {59}, number = {240}, pages = {823-831}, pmid = {34508486}, issn = {1815-672X}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {While the acute case burdens and deaths from the COVID-19 pandemic (in Nepal approaching 700,000 and 10,000 respectively) have been costly, the characteristics and potentially huge dimensions of the chronic disease sequelae of this infectious disease are only slowly becoming apparent. We reviewed Pub Med, major medical meeting and medical journal, and investigative journalist materials seeking to frame and describe COVID-19 chronic disease. The consequences of COVID-19 infections follow major organ damage, and induction of immunological and hormonal systems dysfunction. The first injuries are consequent to direct viral effects on tissues, and vasculitis, endothelialitis, thrombosis and inflammatory events. Pulmonary, cardiac, brain, and kidney tissues incur function-limiting damage, with dyspnea, arrythmias, decreased exercise capacity, cognitive dysfunction, and decreased glomerular filtration rates. The second process is characterized by immune dysregulation and autoimmunity, and dysfunction of hormonal regulation systems, with high, fluctuating levels of physical and mental fatigue, multiple-site pain and ache, and non-restorative sleep, in 10-30% of cases. This communication proposes evaluation and management of chronic COVID-19 patients with efficient assessment of commonest symptoms, targeted physical examination and organ function testing, and interventions based on specific organ functional status, and experience with similar chronic immune syndromes, such as myalgic encephalomyelitis.}, } @article {pmid34506003, year = {2021}, author = {Storz, MA}, title = {Lifestyle Adjustments in Long-COVID Management: Potential Benefits of Plant-Based Diets.}, journal = {Current nutrition reports}, volume = {10}, number = {4}, pages = {352-363}, pmid = {34506003}, issn = {2161-3311}, mesh = {*COVID-19/complications ; Diet, Vegetarian ; Humans ; Life Style ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: The SARS-CoV-2-pandemic has caused mortality and morbidity at an unprecedented global scale. Many patients infected with SARS-CoV-2 continue to experience symptoms after the acute phase of infection and report fatigue, sleep difficulties, anxiety, and depression as well as arthralgia and muscle weakness. Summarized under the umbrella term "long-COVID," these symptoms may last weeks to months and impose a substantial burden on affected individuals. Dietary approaches to tackle these complications have received comparably little attention. Although plant-based diets in particular were shown to exert benefits on underlying conditions linked to poor COVID-19 outcomes, their role with regard to COVID-19 sequelae is yet largely unknown. Thus, this review sought to investigate whether a plant-based diet could reduce the burden of long-COVID.

RECENT FINDINGS: The number of clinical trials investigating the role of plant-based nutrition in COVID-19 prevention and management is currently limited. Yet, there is evidence from pre-pandemic observational and clinical studies that a plant-based diet may be of general benefit with regard to several clinical conditions that can also be found in individuals with COVID-19. These include anxiety, depression, sleep disorders, and musculoskeletal pain. Adoption of a plant-based diet leads to a reduced intake in pro-inflammatory mediators and could be one accessible strategy to tackle long-COVID associated prolonged systemic inflammation. Plant-based diets may be of general benefit with regard to some of the most commonly found COVID-19 sequelae. Additional trials investigating which plant-based eating patterns confer the greatest benefit in the battle against long-COVID are urgently warranted.}, } @article {pmid34505838, year = {2021}, author = {Kvale, G and Frisk, B and Jürgensen, M and Børtveit, T and Ødegaard-Olsen, ØT and Wilhelmsen-Langeland, A and Aarli, BB and Sandnes, K and Rykken, S and Haugstvedt, A and Hystad, SW and Søfteland, E}, title = {Evaluation of Novel Concentrated Interdisciplinary Group Rehabilitation for Patients With Chronic Illnesses: Protocol for a Nonrandomized Clinical Intervention Study.}, journal = {JMIR research protocols}, volume = {10}, number = {10}, pages = {e32216}, pmid = {34505838}, issn = {1929-0748}, abstract = {BACKGROUND: An aging population with a growing burden of chronic complex illnesses will seriously challenge the public health care system. Consequently, novel and efficacious treatment approaches are highly warranted. Based on our experiences with concentrated treatment formats for other health challenges, we developed a highly concentrated interdisciplinary group rehabilitation approach for chronic illnesses.

OBJECTIVE: We aim to explore the acceptability of the intervention and describe potential changes in functional impairment at follow-up.

METHODS: The cornerstones of the intervention are as follows: (1) prepare the patient for change prior to treatment, (2) focus on health promoting microchoices instead of symptoms, and (3) expect the patient to integrate the changes in everyday living with limited hands-on follow-up. The intervention will be delivered to patients with highly diverse primary symptoms, namely patients with low back pain, post-COVID-19 symptoms, anxiety and depression, and type 2 diabetes.

RESULTS: Recruitment started between August 2020 and January 2021 (according to the illness category). For initial 3-month results, recruitment is expected to be completed by the end of 2021.

CONCLUSIONS: If successful, this study may have a substantial impact on the treatment of low back pain, post-COVID-19 symptoms, anxiety and depression, and type 2 diabetes, which together constitute a major socioeconomic cost. Further, the study may widen the evidence base for the use of the concentrated treatment format in a diverse group of medical conditions.

DERR1-10.2196/32216.}, } @article {pmid34505378, year = {2021}, author = {Penninx, BWJH}, title = {Psychiatric symptoms and cognitive impairment in "Long COVID": the relevance of immunopsychiatry.}, journal = {World psychiatry : official journal of the World Psychiatric Association (WPA)}, volume = {20}, number = {3}, pages = {357-358}, pmid = {34505378}, issn = {1723-8617}, } @article {pmid34504319, year = {2021}, author = {Yende, S and Parikh, CR}, title = {Long COVID and kidney disease.}, journal = {Nature reviews. Nephrology}, volume = {17}, number = {12}, pages = {792-793}, pmid = {34504319}, issn = {1759-507X}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {*Acute Kidney Injury/epidemiology/etiology/physiopathology ; COVID-19/*complications/epidemiology ; Delivery of Health Care ; Humans ; Pandemics ; *Renal Insufficiency, Chronic/epidemiology/etiology/physiopathology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Kidney involvement is common in patients with acute SARS-CoV-2 infection, and subclinical inflammation and injury may persist for many months, resulting in a progressive decline in kidney function that leads to chronic kidney disease. Continued research is imperative to understand these long-term sequelae and identify interventions to mitigate them.}, } @article {pmid34504110, year = {2021}, author = {Shetty, AK and Shetty, PA and Zanirati, G and Jin, K}, title = {Further validation of the efficacy of mesenchymal stem cell infusions for reducing mortality in COVID-19 patients with ARDS.}, journal = {NPJ Regenerative medicine}, volume = {6}, number = {1}, pages = {53}, pmid = {34504110}, issn = {2057-3995}, support = {R01 NS106907/NS/NINDS NIH HHS/United States ; R01NS106907//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; W81XWH-16-1-0480//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-14-1-0572//U.S. Department of Defense (United States Department of Defense)/ ; }, abstract = {Recent double-blind, randomized, controlled trials reported that human umbilical cord-derived mesenchymal stem cell (MSC) infusions in COVID-19 patients with acute respiratory distress syndrome (ARDS) could diminish cytokine storm and lung damage. While these outcomes are significant, additional phase II/III trials are required to validate the efficacy of MSCs to improve the survival of COVID-19 patients with ARDS. Future studies also need to assess the efficacy of MSCs to prevent long COVID.}, } @article {pmid34501230, year = {2021}, author = {Kersten, J and Baumhardt, M and Hartveg, P and Hoyo, L and Hüll, E and Imhof, A and Kropf-Sanchen, C and Nita, N and Mörike, J and Rattka, M and Andreß, S and Scharnbeck, D and Schmidtke-Schrezenmeier, G and Tadic, M and Wolf, A and Rottbauer, W and Buckert, D}, title = {Long COVID: Distinction between Organ Damage and Deconditioning.}, journal = {Journal of clinical medicine}, volume = {10}, number = {17}, pages = {}, pmid = {34501230}, issn = {2077-0383}, abstract = {(1) Background: Long COVID syndrome refers to long-term sequelae of the novel viral disease, which occur even in patients with initially mild disease courses. However, there is still little evidence of the actual organic consequences and their frequency, and there is no standardized workup to diagnose long COVID syndrome yet. In this study, we aim to determine the efficiency of a stepwise diagnostic approach for reconvalescent COVID-19 patients with cardiopulmonary symptoms. (2) Methods: The diagnostic workup for long COVID syndrome included three steps. In the first step, the focus was on broad applicability (e.g., blood tests and body plethysmography). In the second step, cardiopulmonary exercise testing (CPET) and cardiac MRI (CMR) were used. The third step was tailored to the individual needs of each patient. The observation period lasted from 22 February to 14 May 2021. (3) Results: We examined 231 patients in our long COVID unit (mean [SD] age, 47.8 [14.9], 132 [57.1%] women). Acute illness occurred a mean (SD) of 121 (77) days previously. Suspicious findings in the first visit were seen in 80 (34.6%) patients, prompting further diagnostics. Thirty-six patients were further examined with CPET and CMR. Of those, 16 (44.4%) had pathological findings. The rest had functional complaints without organ damage ("functional long COVID"). Cardiopulmonary sequelae were found in asymptomatic as well as severe courses of the initial COVID-19 disease. (4) Conclusions: A structured diagnostic pathway for the diagnosis of long COVID syndrome is practicable and rational in terms of resource allocation. With this approach, manifest organ damage can be accurately and comprehensively diagnosed and distinguished from functional complaints.}, } @article {pmid34499626, year = {2021}, author = {Wanga, V and Chevinsky, JR and Dimitrov, LV and Gerdes, ME and Whitfield, GP and Bonacci, RA and Nji, MAM and Hernandez-Romieu, AC and Rogers-Brown, JS and McLeod, T and Rushmore, J and Lutfy, C and Bushman, D and Koumans, E and Saydah, S and Goodman, AB and Coleman King, SM and Jackson, BR and Cope, JR}, title = {Long-Term Symptoms Among Adults Tested for SARS-CoV-2 - United States, January 2020-April 2021.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {70}, number = {36}, pages = {1235-1241}, pmid = {34499626}, issn = {1545-861X}, mesh = {Adolescent ; Adult ; Aged ; COVID-19/*complications/*diagnosis/epidemiology ; COVID-19 Testing/*statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/*isolation & purification ; United States/epidemiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term symptoms often associated with COVID-19 (post-COVID conditions or long COVID) are an emerging public health concern that is not well understood. Prevalence of post-COVID conditions has been reported among persons who have had COVID-19 (range = 5%-80%), with differences possibly related to different study populations, case definitions, and data sources (1). Few studies of post-COVID conditions have comparisons with the general population of adults with negative test results for SARS-CoV-2, the virus that causes COVID-19, limiting ability to assess background symptom prevalence (1). CDC used a nonprobability-based Internet panel established by Porter Novelli Public Services* to administer a survey to a nationwide sample of U.S. adults aged ≥18 years to compare the prevalence of long-term symptoms (those lasting >4 weeks since onset) among persons who self-reported ever receiving a positive SARS-CoV-2 test result with the prevalence of similar symptoms among persons who reported always receiving a negative test result. The weighted prevalence of ever testing positive for SARS-CoV-2 was 22.2% (95% confidence interval [CI] = 20.6%-23.8%). Approximately two thirds of respondents who had received a positive test result experienced long-term symptoms often associated with SARS-CoV-2 infection. Compared with respondents who received a negative test result, those who received a positive test result reported a significantly higher prevalence of any long-term symptom (65.9% versus 42.9%), fatigue (22.5% versus 12.0%), change in sense of smell or taste (17.3% versus 1.7%), shortness of breath (15.5% versus 5.2%), cough (14.5% versus 4.9%), headache (13.8% versus 9.9%), and persistence (>4 weeks) of at least one initially occurring symptom (76.2% versus 69.6%). Compared with respondents who received a negative test result, a larger proportion of those who received a positive test result reported believing that receiving a COVID-19 vaccine made their long-term symptoms better (28.7% versus 15.7%). Efforts to address post-COVID conditions should include helping health care professionals recognize the most common post-COVID conditions and optimize care for patients with persisting symptoms, including messaging on potential benefits of COVID-19 vaccination.}, } @article {pmid34495729, year = {2021}, author = {Bovo, MV}, title = {'Long COVID': Making The Invisible Visible.}, journal = {Health affairs (Project Hope)}, volume = {40}, number = {9}, pages = {1510-1513}, doi = {10.1377/hlthaff.2021.00166}, pmid = {34495729}, issn = {2694-233X}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {After recovering from acute COVID-19 infection, a physician is stricken with the debilitating symptoms of long COVID.}, } @article {pmid34494964, year = {2021}, author = {Van Herck, M and Goërtz, YMJ and Houben-Wilke, S and Machado, FVC and Meys, R and Delbressine, JM and Vaes, AW and Burtin, C and Posthuma, R and Franssen, FME and Hajian, B and Vijlbrief, H and Spies, Y and van 't Hul, AJ and Janssen, DJA and Spruit, MA}, title = {Severe Fatigue in Long COVID: Web-Based Quantitative Follow-up Study in Members of Online Long COVID Support Groups.}, journal = {Journal of medical Internet research}, volume = {23}, number = {9}, pages = {e30274}, pmid = {34494964}, issn = {1438-8871}, mesh = {*COVID-19/complications ; *COVID-19 Testing ; Female ; Follow-Up Studies ; Humans ; Internet ; Middle Aged ; SARS-CoV-2 ; Self-Help Groups ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Fatigue is the most commonly reported symptom in patients with persistent complaints following COVID-19 (ie, long COVID). Longitudinal studies examining the intensity of fatigue and differentiating between physical and mental fatigue are lacking.

OBJECTIVE: The objectives of this study were to (1) assess the severity of fatigue over time in members of online long COVID peer support groups, and (2) assess whether members of these groups experienced mental fatigue, physical fatigue, or both.

METHODS: A 2-wave web-based follow-up study was conducted in members of online long COVID peer support groups with a confirmed diagnosis approximately 3 and 6 months after the onset of infectious symptoms. Demographics, COVID-19 diagnosis, received health care (from medical professionals or allied health care professionals), fatigue (Checklist Individual Strength-subscale subjective fatigue [CIS-Fatigue]; 8-56 points), and physical and mental fatigue (self-constructed questions; 3-21 points) were assessed. Higher scores indicated more severe fatigue. A CIS-Fatigue score ≥36 points was used to qualify patients as having severe fatigue.

RESULTS: A total of 239 patients with polymerase chain reaction/computed tomography-confirmed COVID-19 completed the survey 10 weeks (SD 2) and 23 weeks (SD 2) after onset of infectious symptoms, respectively (T1 and T2). Of these 239 patients, 198 (82.8%) were women; 142 (59.4%) had no self-reported pre-existing comorbidities; 208 (87%) self-reported being in good health before contracting COVID-19; and 62 (25.9%) were hospitalized during acute infection. The median age was 50 years (IQR 39-56). The vast majority of patients had severe fatigue at T1 and T2 (n=204, 85.4%, and n=188, 78.7%, respectively). No significant differences were found in the prevalence of normal, mild, and severe fatigue between T1 and T2 (P=.12). The median CIS-Fatigue score was 48 points (IQR 42-53) at T1, and it decreased from T1 to T2 (median change: -2 points, IQR -7 to 3; P<.001). At T1, a median physical fatigue score of 19 points (IQR 16-20) and a median mental fatigue score of 15 points (IQR 10-17) were reported; these scores were lower at T2 for physical but not for mental fatigue (median change for physical fatigue -1 point, IQR -3 to 0, P<.001; median change for mental fatigue 0 points, IQR -3 to 3, P=.52). At the time of completing the follow-up survey, 194/239 (81.2%) and 164/239 (68.6%) of all patients had received care from at least one medical professional and one allied health care professional, respectively.

CONCLUSIONS: Fatigue in members of online long COVID support groups with a confirmed COVID-19 diagnosis decreases from 10 to 23 weeks after onset of symptoms. Despite this, severe fatigue remains highly prevalent. Both physical and mental fatigue are present. It remains unclear whether and to what extent fatigue will resolve spontaneously in the longer term.

TRIAL REGISTRATION: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705.}, } @article {pmid34492712, year = {2021}, author = {Richter, D and Zürcher, S}, title = {[Long Covid/Post Covid - Epidemiology, Possible Causes and Need for Rehabilitation for People with Mental Health Problems].}, journal = {Psychiatrische Praxis}, volume = {48}, number = {6}, pages = {283-285}, doi = {10.1055/a-1545-9441}, pmid = {34492712}, issn = {1439-0876}, mesh = {*COVID-19/complications ; Germany ; Humans ; *Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34488505, year = {2021}, author = {Razai, MS and Al-Bedaery, R and Anand, L and Fitch, K and Okechukwu, H and Saraki, TM and Oakeshott, P}, title = {Patients' Experiences of "Long COVID" in the Community and Recommendations for Improving Services: A Quality Improvement Survey.}, journal = {Journal of primary care & community health}, volume = {12}, number = {}, pages = {21501327211041846}, pmid = {34488505}, issn = {2150-1327}, mesh = {*COVID-19/complications ; Humans ; *Quality Improvement ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: "Long COVID" is a multisystem disease that lasts for 4 or more weeks following initial symptoms of COVID-19. In the UK, at least 10% of patient report symptoms at 12 weeks following a positive COVID-19 test. The aims of this quality improvement survey were to explore patients' acute and post-acute "long" COVID-19 symptoms, their experiences of community services and their recommendations for improving these services.

METHODS: Seventy patients diagnosed with COVID were randomly selected from 2 large socially and ethnically diverse primary care practices. Of those contactable by telephone, 85% (41/48) agreed to participate in the quality improvement survey. They were interviewed by telephone using a semi-structured questionnaire about community services for COVID-19 patients. Interviews lasted 10 to 15 minutes.

RESULTS: Forty-nine percent of patients reported at least 1 post-acute COVID-19 symptom. The most common were severe fatigue (45%), breathlessness (30%), neurocognitive difficulties (such as poor memory), poor concentration and "brain fog" (30%), headaches (20%), and joint pain (20%). Many patients felt isolated and fearful, with scant information about community resources and little safety netting advice. Patients also expected more from primary care with over half (56%) recommending regular phone calls and follow up from healthcare staff as the most important approach in their recovery.

CONCLUSIONS: In line with patients' requests for more support, the practices now routinely refer patients with long COVID to an on-site social prescriber who explores how they are getting on, refers them to the GP or practice nurse when required, and sign posts them to support services in the community.}, } @article {pmid34485849, year = {2021}, author = {Sarker, A and Ge, Y}, title = {Mining long-COVID symptoms from Reddit: characterizing post-COVID syndrome from patient reports.}, journal = {JAMIA open}, volume = {4}, number = {3}, pages = {ooab075}, pmid = {34485849}, issn = {2574-2531}, abstract = {Our objective was to mine Reddit to discover long-COVID symptoms self-reported by users, compare symptom distributions across studies, and create a symptom lexicon. We retrieved posts from the /r/covidlonghaulers subreddit and extracted symptoms via approximate matching using an expanded meta-lexicon. We mapped the extracted symptoms to standard concept IDs, compared their distributions with those reported in recent literature and analyzed their distributions over time. From 42 995 posts by 4249 users, we identified 1744 users who expressed at least 1 symptom. The most frequently reported long-COVID symptoms were mental health-related symptoms (55.2%), fatigue (51.2%), general ache/pain (48.4%), brain fog/confusion (32.8%), and dyspnea (28.9%) among users reporting at least 1 symptom. Comparison with recent literature revealed a large variance in reported symptoms across studies. Temporal analysis showed several persistent symptoms up to 15 months after infection. The spectrum of symptoms identified from Reddit may provide early insights about long-COVID.}, } @article {pmid34485048, year = {2021}, author = {Mitrani, MI and Bellio, MA and Meglin, A and Khan, A and Xu, X and Haskell, G and Arango, A and Shapiro, GC}, title = {Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic.}, journal = {Respiratory medicine case reports}, volume = {34}, number = {}, pages = {101502}, pmid = {34485048}, issn = {2213-0071}, abstract = {Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients' lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.}, } @article {pmid34484759, year = {2021}, author = {Bekbossynova, M and Ainur, T}, title = {Hypertension as a manifestation of COVID-19 pneumonia.}, journal = {Clinical case reports}, volume = {9}, number = {9}, pages = {e04720}, pmid = {34484759}, issn = {2050-0904}, abstract = {Several factors such as hypertension, bile duct disease, and age can affect the duration of COVID, which can lead to long COVID. Any course of coronavirus infection could have a diverse nature of clinical forms and should have a personalized approach.}, } @article {pmid34478045, year = {2021}, author = {Asadi-Pooya, AA and Nemati, H and Shahisavandi, M and Akbari, A and Emami, A and Lotfi, M and Rostamihosseinkhani, M and Barzegar, Z and Kabiri, M and Zeraatpisheh, Z and Farjoud-Kouhanjani, M and Jafari, A and Sasannia, F and Ashrafi, S and Nazeri, M and Nasiri, S}, title = {Long COVID in children and adolescents.}, journal = {World journal of pediatrics : WJP}, volume = {17}, number = {5}, pages = {495-499}, pmid = {34478045}, issn = {1867-0687}, mesh = {Adolescent ; COVID-19/*complications/diagnosis/epidemiology ; Child ; Cross-Sectional Studies ; Female ; Humans ; Iran/epidemiology ; Male ; Prevalence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: To identify the prevalence and also the full spectrum of symptoms/complaints of children and adolescents who are suffering from long COVID. Furthermore, we investigated the risk factors of long COVID in children and adolescents.

METHODS: All consecutive children and adolescents who were referred to the hospitals anywhere in Fars province, Iran, from 19 February 2020 until 20 November 2020 were included. All patients had a confirmed diagnosis of COVID-19. In a phone call to patients/parents, at least 3 months after their discharge from the hospital, we obtained their current status and information if their parents agreed to participate.

RESULTS: In total, 58 children and adolescents fulfilled the inclusion criteria. Twenty-six (44·8%) children/adolescents reported symptoms/complaints of long COVID. These symptoms included fatigue in 12 (21%), shortness of breath in 7 (12%), exercise intolerance in 7 (12%), weakness in 6 (10%), and walking intolerance in 5 (9%) individuals. Older age, muscle pain on admission, and intensive care unit admission were significantly associated with long COVID.

CONCLUSIONS: Long COVID is a frequent condition in children and adolescents. The scientific community should investigate and explore the pathophysiology of long COVID to ensure that these patients receive appropriate treatments for their condition.}, } @article {pmid34474488, year = {2021}, author = {Koczulla, AR and Ankermann, T and Behrends, U and Berlit, P and Böing, S and Brinkmann, F and Franke, C and Glöckl, R and Gogoll, C and Hummel, T and Kronsbein, J and Maibaum, T and Peters, EMJ and Pfeifer, M and Platz, T and Pletz, M and Pongratz, G and Powitz, F and Rabe, KF and Scheibenbogen, C and Stallmach, A and Stegbauer, M and Wagner, HO and Waller, C and Wirtz, H and Zeiher, A and Zwick, RH}, title = {[S1 Guideline Post-COVID/Long-COVID].}, journal = {Pneumologie (Stuttgart, Germany)}, volume = {75}, number = {11}, pages = {869-900}, doi = {10.1055/a-1551-9734}, pmid = {34474488}, issn = {1438-8790}, mesh = {*COVID-19/complications ; Consensus ; Humans ; *Pulmonary Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.}, } @article {pmid34473556, year = {2021}, author = {Robinson, P}, title = {Long COVID and breathlessness: an overview.}, journal = {British journal of community nursing}, volume = {26}, number = {9}, pages = {438-443}, doi = {10.12968/bjcn.2021.26.9.438}, pmid = {34473556}, issn = {1462-4753}, mesh = {COVID-19/*complications/nursing/physiopathology ; *Community Health Nursing ; *Dyspnea/etiology/nursing ; Humans ; Palliative Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {This article offers a review of what is known so far about post-acute covid-19 and the underlying pathophysiology related to this condition. The main focus will be on the respiratory symptoms. It will then explore how community nurses can monitor and support patients with symptoms of breathlessness with a supporting discussion of the current recommendations for the management and treatment of patients presenting with symptoms of breathlessness. Palliation of symptoms will be highlighted but managing the supportive care needs for patients affected by COVID-19 and nearing the end of life is outside the scope of this article.}, } @article {pmid34473245, year = {2022}, author = {Wynberg, E and van Willigen, HDG and Dijkstra, M and Boyd, A and Kootstra, NA and van den Aardweg, JG and van Gils, MJ and Matser, A and de Wit, MR and Leenstra, T and de Bree, G and de Jong, MD and Prins, M and , }, title = {Evolution of Coronavirus Disease 2019 (COVID-19) Symptoms During the First 12 Months After Illness Onset.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {75}, number = {1}, pages = {e482-e490}, pmid = {34473245}, issn = {1537-6591}, mesh = {Adolescent ; Adult ; *COVID-19/diagnosis ; Female ; Humans ; Male ; Proportional Hazards Models ; Prospective Studies ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {BACKGROUND: Few robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset.

METHODS: The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.

RESULTS: Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI}  = 76.5-92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1-40.9%] and 63.8% [95% CI = 54.8-71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2-7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47-.92]) and those with a body mass index [BMI]  ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39-.97]).

CONCLUSIONS: COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.}, } @article {pmid34471633, year = {2021}, author = {Gloeckl, R and Leitl, D and Jarosch, I and Schneeberger, T and Nell, C and Stenzel, N and Daher, A and Dreher, M and Vogelmeier, CF and Kenn, K and Koczulla, AR}, title = {Pulmonary rehabilitation in long COVID: more than just natural recovery!?.}, journal = {ERJ open research}, volume = {7}, number = {3}, pages = {}, pmid = {34471633}, issn = {2312-0541}, abstract = {In the light of missing randomised controlled trials, some arguments suggest that pulmonary rehabilitation has beneficial effects beyond natural recovery https://bit.ly/3ze2xvw.}, } @article {pmid34471377, year = {2021}, author = {Elkan, M and Dvir, A and Zaidenstein, R and Keller, M and Kagansky, D and Hochman, C and Koren, R}, title = {Patient-Reported Outcome Measures After Hospitalization During the COVID-19 Pandemic: A Survey Among COVID-19 and Non-COVID-19 Patients.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {4829-4836}, pmid = {34471377}, issn = {1178-7074}, abstract = {BACKGROUND: Many people recovering from COVID-19 suffer from long-term sequelae. The objective of this study was to assess health-related quality of life (HRQoL) in COVID-19 patients several months after discharge.

METHODS: We conducted a retrospective cross-sectional case-control study on COVID-19 and non-COVID-19 pneumonia patients admitted to Shamir Medical Center, Israel (03-07/2020). In the months following discharge, patients were invited to participate in a survey and fill the RAND-36 questionnaire. Patients' characteristics and comorbidities were extracted from electronic charts.

RESULTS: Among 66 COVID-19 participants, the median age was 58.5 (IQR 49.8-68.3), 56.1% were female, and 36.4% were obese. The median length of stay was 7 days (IQR 4-10). Patient-reported outcome measures were reported at a median follow-up of 9-months (IQR 6-9). Pain, general health, vitality, and health change had the lowest scores (67.5, 60, 57.5, and 25, respectively). Matching to patients hospitalized with pneumonia due to other pathogens was performed on 42 of the COVID-19 patients. Non-COVID-19 patients were more frequently current or past smokers (50% vs 11.9%, p < 0.01) and suffered more often from chronic lung disease (38.1% vs 9.5%, p = 0.01). The score for health change was significantly lower in the COVID-19 group (25 vs 50, p < 0.01).

CONCLUSION: Post COVID-19 patients continue to suffer from an assortment of symptoms and perceive a deterioration in their health many months after hospitalization. This emphasizes the importance of prolonged medical follow-up in this population, and the need for additional research to better understand this novel disease's long-term effects.}, } @article {pmid34470828, year = {2021}, author = {Bowe, B and Xie, Y and Xu, E and Al-Aly, Z}, title = {Kidney Outcomes in Long COVID.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {32}, number = {11}, pages = {2851-2862}, pmid = {34470828}, issn = {1533-3450}, mesh = {Aged ; COVID-19/*complications/diagnosis/epidemiology/therapy ; Case-Control Studies ; Cohort Studies ; Critical Care ; Female ; Glomerular Filtration Rate ; Hospitalization ; Humans ; Kidney Diseases/diagnosis/*epidemiology/*virology ; Male ; Middle Aged ; United States ; Veterans/*statistics & numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available.

METHODS: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory.

RESULTS: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m[2] per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection.

CONCLUSIONS: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.}, } @article {pmid34470745, year = {2021}, author = {Wise, J}, title = {Long covid: One in seven children may still have symptoms 15 weeks after infection, data show.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n2157}, doi = {10.1136/bmj.n2157}, pmid = {34470745}, issn = {1756-1833}, } @article {pmid34463956, year = {2022}, author = {Malik, P and Patel, K and Pinto, C and Jaiswal, R and Tirupathi, R and Pillai, S and Patel, U}, title = {Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.}, journal = {Journal of medical virology}, volume = {94}, number = {1}, pages = {253-262}, pmid = {34463956}, issn = {1096-9071}, mesh = {Adult ; Age Factors ; COVID-19/*complications ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.}, } @article {pmid34456621, year = {2021}, author = {Richter, K and Kellner, S}, title = {["Coronasomnia"-promoting resilience through insomnia treatment].}, journal = {Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine}, volume = {25}, number = {3}, pages = {170-175}, pmid = {34456621}, issn = {1432-9123}, abstract = {BACKGROUND: The term "coronasomnia" is used in popular science to describe sleep disorders associated with the COVID-19 pandemic. These disorders may also affect part of the population in the aftermath of the pandemic. Early scientific evidence suggests that COVID-19-associated insomnia and insomniac symptoms can become chronic and will continue to preoccupy the sleep medicine community even after the pandemic has ended.

METHODS: A literature review was conducted in Medline and Google Scholar using the following combination of keywords: "insomnia and COVID-19", "insomnia and long COVID", "insomnia, PTSD and COVID-19", and "fatigue and insomnia in long COVID". In addition, the authors reviewed several recent articles published by members of the European Insomnia Network.

RESULTS: Studies on insomnia and COVID-19 show significant associations between acute infection and insomnia in affected individuals. The prevalence of insomnia symptoms in COVID-19-affected individuals was 36 to 88%, which is significantly higher than the estimated 10 to 40% prevalence of insomnia in the general population.

CONCLUSION: Digital therapy as a current treatment option for insomnia can be offered to patients regardless of physical distance. Accordingly, not only early approval of therapy apps, but also person-led, digital therapy options for insomnia would be recommended. The inclusion of personalised and sleep-coaching measures in the area of occupational health management is encouraged.}, } @article {pmid34454656, year = {2021}, author = {The Lancet, }, title = {Understanding long COVID: a modern medical challenge.}, journal = {Lancet (London, England)}, volume = {398}, number = {10302}, pages = {725}, doi = {10.1016/S0140-6736(21)01900-0}, pmid = {34454656}, issn = {1474-547X}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34452963, year = {2021}, author = {Henningsen, MJ and Khatam-Lashgari, A and Olsen, KB and Jacobsen, C and Brøchner, CB and Banner, J}, title = {Translational deep phenotyping of deaths related to the COVID-19 pandemic: protocol for a prospective observational autopsy study.}, journal = {BMJ open}, volume = {11}, number = {8}, pages = {e049083}, pmid = {34452963}, issn = {2044-6055}, mesh = {Autopsy ; *COVID-19 ; Humans ; *Pandemics ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: The COVID-19 pandemic is an international emergency with an extreme socioeconomic impact and a high mortality and disease burden. The COVID-19 outbreak is neither fully understood nor fully pictured. Autopsy studies can help understand the pathogenesis of COVID-19 and has already resulted in better treatment of patients. Structured and systematic autopsy of COVID-19-related deaths will enhance the mapping of pathophysiological pathways, not possible in the living. Furthermore, it provides an opportunity to envision factors translationally for the purpose of disease prevention in this and future pandemics. This is the protocol for an autopsy study that offers an umbrella for deep and diverse investigations of COVID-19-related deaths, including a systematic investigation of 'long' COVID-19 by means of extensive and systematic tissue sampling.

METHODS AND ANALYSIS: A COVID-19-specific autopsy algorithm has been created to cover all cases undergoing clinical or forensic autopsy in Denmark. The algorithm describes advanced tissue sampling and a translational analytical follow-up for deep phenotyping. The translational approach covers registry data, postmortem imaging, gross autopsy findings, microscopic organ changes, postmortem toxicology, postmortem biochemical investigation, microbiological profiling and immunological status at the time of death, and future research projects covering genetics and epigenetics on an organ level.

ETHICS AND DISSEMINATION: This study has been approved by the Regional Ethics Committee of the Region of Greater Copenhagen (No: H-20078436) and the Danish Data Protection Agency (No: 2002-54-1080). Next of kin gave informed consent to research. The study results will be published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: This study is purely observational and, as such, does not meet the criteria of the International Committee of Medical Journal Editors for clinical trials; thus, there is no need for registration in a database of research trials, such as clinical trials. To facilitate cooperation in research, provide transparency on case recruitment for publications to come and to avoid unnecessary duplicate work, we nevertheless wish to publish our protocol.}, } @article {pmid34452458, year = {2021}, author = {Grehl, C and Schultheiß, C and Hoffmann, K and Binder, M and Altmann, T and Grosse, I and Kuhlmann, M}, title = {Detection of SARS-CoV-2 Derived Small RNAs and Changes in Circulating Small RNAs Associated with COVID-19.}, journal = {Viruses}, volume = {13}, number = {8}, pages = {}, pmid = {34452458}, issn = {1999-4915}, support = {CRC 841//Deutsche Forschungsgemeinschaft/ ; }, mesh = {COVID-19/*blood/complications/genetics/*virology ; Cell-Free Nucleic Acids/*blood ; Female ; Genome, Viral ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; MicroRNAs/*blood/genetics ; RNA, Viral/*blood/genetics ; SARS-CoV-2/*genetics ; Severity of Illness Index ; Viral Nonstructural Proteins/genetics ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3'-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm.}, } @article {pmid34446892, year = {2021}, author = {Agar, S and Morgan, E and Lee, Y}, title = {A further plot twist: will 'long COVID' have an impact on dentistry and the dental workforce?.}, journal = {British dental journal}, volume = {231}, number = {4}, pages = {221-224}, pmid = {34446892}, issn = {1476-5373}, mesh = {*COVID-19/complications ; Dentistry ; Humans ; SARS-CoV-2 ; Workforce ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 has dominated our lives since the start of the pandemic in 2020, as well as greatly impacting dentistry, its patients and the dental profession. A new and potentially further problematic phenomenon is that of long COVID, a term used to describe the effects of COVID-19 that continue for weeks, or even months, beyond the initial illness. It is characterised by debilitating symptoms including extreme fatigue, shortness of breath, insomnia, heart palpitations and prolonged high temperature. With one in ten people in the UK suffering from long COVID, there will undoubtedly be a considerable impact on dentistry provision; there will be ramifications not only for patients, but also the workforce, both physically and mentally. The aim of this article is to explore the obstacles we will face due to long COVID, examining possible challenges but also possible solutions.}, } @article {pmid34446502, year = {2021}, author = {Stephenson, T and Shafran, R and De Stavola, B and Rojas, N and Aiano, F and Amin-Chowdhury, Z and McOwat, K and Simmons, R and Zavala, M and Consortium, C and Ladhani, SN and , }, title = {Long COVID and the mental and physical health of children and young people: national matched cohort study protocol (the CLoCk study).}, journal = {BMJ open}, volume = {11}, number = {8}, pages = {e052838}, pmid = {34446502}, issn = {2044-6055}, support = {G108/625/MRC_/Medical Research Council/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; *COVID-19/complications ; Child ; Cohort Studies ; Humans ; Prevalence ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: There is uncertainty surrounding the diagnosis, prevalence, phenotype, duration and treatment of Long COVID. This study aims to (A) describe the clinical phenotype of post-COVID symptomatology in children and young people (CYP) with laboratory-confirmed SARS-CoV-2 infection compared with test-negative controls, (B) produce an operational definition of Long COVID in CYP, and (C) establish its prevalence in CYP.

METHODS AND ANALYSIS: A cohort study of SARS-CoV-2-positive CYP aged 11-17 years compared with age, sex and geographically matched SARS-CoV-2 test-negative CYP. CYP aged 11-17 testing positive and negative for SARS-CoV-2 infection will be identified and contacted 3, 6, 12 and 24 months after the test date. Consenting CYP will complete an online questionnaire. We initially planned to recruit 3000 test positives and 3000 test negatives but have since extended our target. Data visualisation techniques will be used to examine trajectories over time for symptoms and variables measured repeatedly, separately by original test status. Summary measures of fatigue and mental health dimensions will be generated using dimension reduction methods such as latent variables/latent class/principal component analysis methods. Cross-tabulation of collected and derived variables against test status and discriminant analysis will help operationalise preliminary definitions of Long COVID.

ETHICS AND DISSEMINATION: Research Ethics Committee approval granted. Data will be stored in secure Public Health England servers or University College London's Data Safe Haven. Risks of harm will be minimised by providing information on where to seek support. Results will be published on a preprint server followed by journal publication, with reuse of articles under a CC BY licence. Data will be published with protection against identification when there are small frequencies involved.

TRIAL REGISTRATION NUMBER: ISRCTN34804192; Pre-results.}, } @article {pmid34445238, year = {2021}, author = {Schomburg, L}, title = {Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trigger for Autoimmune Disease.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445238}, issn = {1422-0067}, support = {Research Unit FOR-2558 "TraceAge" (Scho 849/6-2)//Deutsche Forschungsgemeinschaft/ ; CRC/TR 296 "Local control of TH action" (LocoTact, P17)//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Autoimmune Diseases/*drug therapy ; Dietary Supplements ; Female ; Humans ; Immune System/*drug effects ; Pregnancy ; Selenium/*pharmacology ; Trace Elements/*pharmacology ; *COVID-19 Drug Treatment ; }, abstract = {The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.}, } @article {pmid34444477, year = {2021}, author = {Scheiber, B and Spiegl, C and Wiederin, C and Schifferegger, E and Schiefermeier-Mach, N}, title = {Post-COVID-19 Rehabilitation: Perception and Experience of Austrian Physiotherapists and Physiotherapy Students.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {16}, pages = {}, pmid = {34444477}, issn = {1660-4601}, mesh = {Austria ; *COVID-19/complications ; Cross-Sectional Studies ; Humans ; Perception ; *Physical Therapists ; Physical Therapy Modalities ; SARS-CoV-2 ; Students ; Post-Acute COVID-19 Syndrome ; }, abstract = {The rehabilitation needs of COVID-19 survivors are increasingly recognized, with a focus on combating respiratory and neuromuscular dysfunctions. The aim here was to explore the perception of Austrian physiotherapists and physiotherapy students on post-COVID-19 rehabilitation care and to identify barriers for the application of sufficient rehabilitation. We analysed current knowledge and practical skills in respiratory physiotherapy, performing a cross-sectional national survey among physiotherapists working in outpatient settings and physiotherapy students in their last academic year of bachelor-level education in Austria. Out of 255 survey participants, one-third already had inquiries to treat post-COVID-19 patients, and the majority of respondents expected a further increased inflow of patients with rehabilitation needs (64.2%). Only 11.2% of respondents reported feeling sufficiently informed about post-COVID-19 rehabilitation. A total of 68.2% of students and up to 48.1% of physiotherapists favoured a COVID-19-specific adaptation already in the basic academic education, and 74.1% of survey participants indicated interest in attending specific training. Concerning respiratory physiotherapy, our data showed discrepancies between the estimation of the importance of specific examination and treatment techniques and the level of current experience. There is a clear lack of experience in implementing effective device-based respiratory therapy. Our data indicate an urgent need to develop new education and training programs with a focus on the interdisciplinary rehabilitation of patients with post-COVID-19 syndrome.}, } @article {pmid34442798, year = {2021}, author = {Zayet, S and Zahra, H and Royer, PY and Tipirdamaz, C and Mercier, J and Gendrin, V and Lepiller, Q and Marty-Quinternet, S and Osman, M and Belfeki, N and Toko, L and Garnier, P and Pierron, A and Plantin, J and Messin, L and Villemain, M and Bouiller, K and Klopfenstein, T}, title = {Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comté Hospital, France.}, journal = {Microorganisms}, volume = {9}, number = {8}, pages = {}, pmid = {34442798}, issn = {2076-2607}, abstract = {(1) Background.&nbsp;Post-COVID-19 syndrome is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection. (2) Methods. ANOSVID is an observational retrospective study in Nord Franche-Comté Hospital in France that included adult COVID-19 patients confirmed by RT-PCR from 1 March 2020 to 31 May 2020. The aim was to describe patients with post-COVID-19 syndrome with persistent symptoms (PS group) and to compare them with the patients without persistent symptoms (no-PS group). (3) Results. Of the 354 COVID-19 patients, 35.9% (n = 127) reported persistence of at least one symptom after a mean of 289.1 ± 24.5 days after symptom onset. Moreover, 115 patients reported a recurrence of symptoms after recovery, and only 12 patients reported continuous symptoms. The mean age of patients was 48.6 years (19-93) ± 19.4, and 81 patients (63.8%) were female. Patients in the PS group had a longer duration of symptoms of initial acute SARS-CoV-2 infection than patients in the no-PS group (respectively, 57.1 ± 82.1 days versus 29.7 ± 42.1 days, p < 0.001). A majority of patients (n = 104, 81.9%) reported three or more symptoms. The most prevalent persistent symptoms were loss of smell (74.0%, n = 94), fatigue (53.5%, n = 68), loss of taste (31.5%, n = 40), and dyspnea (30.7%, n = 39). These were followed by pain symptoms (26.8% (n = 34), 26.0% (n = 33), 24.4% (n = 31); headache, arthralgia, and myalgia, respectively). More than half of patients reporting persistent symptoms (58%, n = 73) were healthcare workers (HCWs). Among outpatients, this population was more present in the PS group than the no-PS group ((86.6%) n = 71/82 versus (72.2%) n = 109/151, p = 0.012). Post-COVID-19 syndrome was more frequent in patients with a past history of chronic rhinosinusitis (8.7% (n = 11%) versus 1.3% (n = 3), p < 0.001). No significant difference was found regarding clinical characteristics and outcome, laboratory, imaging findings, and treatment received in the two groups. (4) Conclusions. More than a third of our COVID-19 patients presented persistent symptoms after SARS-CoV-2 infection, particularly through loss of smell, loss of taste, fatigue, and dyspnea, with a high prevalence in HCWs among COVID-19 outpatients.}, } @article {pmid34442710, year = {2021}, author = {Balzanelli, MG and Distratis, P and Dipalma, G and Vimercati, L and Inchingolo, AD and Lazzaro, R and Aityan, SK and Maggiore, ME and Mancini, A and Laforgia, R and Pezzolla, A and Tomassone, D and Pham, VH and Iacobone, D and Castrignano, A and Scarano, A and Lorusso, F and Tafuri, S and Migliore, G and Inchingolo, AM and Nguyen, KCD and Toai, TC and Inchingolo, F and Isacco, CG}, title = {Sars-CoV-2 Virus Infection May Interfere CD34+ Hematopoietic Stem Cells and Megakaryocyte-Erythroid Progenitors Differentiation Contributing to Platelet Defection towards Insurgence of Thrombocytopenia and Thrombophilia.}, journal = {Microorganisms}, volume = {9}, number = {8}, pages = {}, pmid = {34442710}, issn = {2076-2607}, abstract = {To date, several cases of thrombosis have been confirmed to be related to Sars-CoV-2 infection. Multiple attempts detected the prolonged occurrence of Sars-CoV-2 viral RNA (long COVID) in whole blood suggesting that virus byproducts may remain within cells and tissues well over the disease has finished. Patients may develop severe thrombocytopenia, acute anemia of inflammation and, systemic thrombosis with the fatal course of disease, which is suggestive of further interferences of Sars-CoV-2 on hematopoietic stem cells (HSCs) within the differentiation process towards erythroid and megakaryocytic cells. Therefore, we speculated whether Sars-CoV-2 propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells as the main cause of thrombotic events in either COVID-19 patients or vaccinated individuals. Results: The Sars-CoV-2 RNA replication, protein translation and infectious particle formation as the spike proteins in hematopoietic cell lines take place via the angiotensin-converting enzyme 2 (ACE2) entry pathway within primary CD34[+] HSCs inducing, ex vivo, the formation of defected erythroid and megakaryocytic cells that eventually become targets of humoral and adaptive immune cells. Conclusions: Viral particles from affected CD34[+] HSCs or the cellular component of RBC units and eventually platelets, present the greatest risk for sever thrombosis-transmitted Sars-CoV-2 infections.}, } @article {pmid34442450, year = {2021}, author = {Stavrou, VT and Tourlakopoulos, KN and Vavougios, GD and Papayianni, E and Kiribesi, K and Maggoutas, S and Nikolaidis, K and Fradelos, EC and Dimeas, I and Daniil, Z and Gourgoulianis, KI and Boutlas, S}, title = {Eight Weeks Unsupervised Pulmonary Rehabilitation in Previously Hospitalized of SARS-CoV-2 Infection.}, journal = {Journal of personalized medicine}, volume = {11}, number = {8}, pages = {}, pmid = {34442450}, issn = {2075-4426}, abstract = {The aim of our study was to determine the impact of unsupervised Pulmonary Rehabilitation (uns-PR) on patients recovering from COVID-19, and determine its anthropometric, biological, demographic and fitness correlates. All patients (n = 20, age: 64.1 ± 9.9 years, 75% male) participated in unsupervised Pulmonary Rehabilitation program for eight weeks. We recorded anthropometric characteristics, pulmonary function parameters, while we performed 6 min walk test (6 MWT) and blood sampling for oxidative stress measurement before and after uns-PR. We observed differences before and after uns-PR during 6 MWT in hemodynamic parameters [systolic blood pressure in resting (138.7 ± 16.3 vs. 128.8 ± 8.6 mmHg, p = 0.005) and end of test (159.8 ± 13.5 vs. 152.0 ± 12.2 mmHg, p = 0.025), heart rate (5th min: 111.6 ± 16.9 vs. 105.4 ± 15.9 bpm, p = 0.049 and 6th min: 112.5 ± 18.3 vs. 106.9 ± 17.9 bpm, p = 0.039)], in oxygen saturation (4th min: 94.6 ± 2.9 vs. 95.8 ± 3.2%, p = 0.013 and 1st min of recovery: 97.8 ± 0.9 vs. 97.3 ± 0.9%), in dyspnea at the end of 6 MWT (1.3 ± 1.5 vs. 0.6 ± 0.9 score, p = 0.005), in distance (433.8 ± 102.2 vs. 519.2 ± 95.4 m, p < 0.001), in estimated O2 uptake (14.9 ± 2.4 vs. 16.9 ± 2.2 mL/min/kg, p < 0.001) in 30 s sit to stand (11.4 ± 3.2 vs. 14.1 ± 2.7 repetitions, p < 0.001)] Moreover, in plasma antioxidant capacity (2528.3 ± 303.2 vs. 2864.7 ± 574.8 U.cor., p = 0.027), in body composition parameters [body fat (32.2 ± 9.4 vs. 29.5 ± 8.2%, p = 0.003), visceral fat (14.0 ± 4.4 vs. 13.3 ± 4.2 score, p = 0.021), neck circumference (39.9 ± 3.4 vs. 37.8 ± 4.2 cm, p = 0.006) and muscle mass (30.1 ± 4.6 vs. 34.6 ± 7.4 kg, p = 0.030)] and sleep quality (6.7 ± 3.9 vs. 5.6 ± 3.3 score, p = 0.036) we observed differences before and after uns-PR. Our findings support the implementation of unsupervised pulmonary rehabilitation programs in patients following COVID-19 recovery, targeting the improvement of many aspects of long COVID-19 syndrome.}, } @article {pmid34440903, year = {2021}, author = {Hirschenberger, M and Hunszinger, V and Sparrer, KMJ}, title = {Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections.}, journal = {Cells}, volume = {10}, number = {8}, pages = {}, pmid = {34440903}, issn = {2073-4409}, support = {IMMUNOMOD//Bundesministerium für Bildung und Forschung/ ; SP1600/4-1//Deutsche Forschungsgemeinschaft/ ; SPP1923//Deutsche Forschungsgemeinschaft/ ; CRC1279//Deutsche Forschungsgemeinschaft/ ; }, mesh = {COVID-19/*immunology/physiopathology ; Cytokines ; Disease Progression ; Humans ; Immunity, Innate/*immunology ; Inflammation ; }, abstract = {Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.}, } @article {pmid34440170, year = {2021}, author = {Yan, Z and Yang, M and Lai, CL}, title = {Long COVID-19 Syndrome: A Comprehensive Review of Its Effect on Various Organ Systems and Recommendation on Rehabilitation Plans.}, journal = {Biomedicines}, volume = {9}, number = {8}, pages = {}, pmid = {34440170}, issn = {2227-9059}, abstract = {The majority of people infected with SARS-CoV-2 fully recovered within a few weeks. However, a considerable number of patients of different ages still suffer from long-lasting problems similar to the multi-organ damage in its acute phase of infection, or experience symptoms continuously for a longer term after the recovery. The severity of the primary infection seems not to be associated with the possibility and severity of long-term symptoms. Various unresolved symptoms have been reported in COVID-19 survivors months after hospital discharge. Long COVID-19 Syndrome refers to survivors 4 months after initial symptoms onset. It is important to understand the systemic effects of Long COVID-19 Syndrome, its presentations, and the need for rehabilitations to restore functional recovery in survivors. Government, healthcare workers, and survivor groups should collaborate to establish a self-sustaining system to facilitate follow-up and rehabilitations, with prioritization of resources to more severely Long COVID-19 Syndrome survivors. This review looks into the systemic effects of Long COVID-19 Syndrome in various aspects: respiratory, cardiovascular, hematological, renal, gastrointestinal, neurological, and metabolic effects of Long COVID-19 Syndromes. Recommendations for follow-up and rehabilitations details have been explored to cope with the tremendous Long COVID-19 Syndrome patients.}, } @article {pmid34437746, year = {2021}, author = {Dearing, L and Müller, F and Sellner, J}, title = {Headache with SARS-CoV-2 infection: A matter of concern.}, journal = {European journal of neurology}, volume = {28}, number = {11}, pages = {3554-3555}, pmid = {34437746}, issn = {1468-1331}, mesh = {*COVID-19 ; Headache/etiology ; Humans ; *SARS-CoV-2 ; }, } @article {pmid34437579, year = {2021}, author = {Søraas, A and Kalleberg, KT and Dahl, JA and Søraas, CL and Myklebust, TÅ and Axelsen, E and Lind, A and Bævre-Jensen, R and Jørgensen, SB and Istre, MS and Kjetland, EF and Ursin, G}, title = {Persisting symptoms three to eight months after non-hospitalized COVID-19, a prospective cohort study.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0256142}, pmid = {34437579}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; COVID-19/*complications/etiology/*pathology/virology ; Fatigue/etiology ; Female ; Fever/etiology ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; RNA, Viral/analysis/metabolism ; Real-Time Polymerase Chain Reaction ; SARS-CoV-2/genetics/isolation & purification ; Self Report ; Surveys and Questionnaires ; Time Factors ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID-19 is a proposed syndrome negatively affecting the health of COVID-19 patients. We present data on self-rated health three to eight months after laboratory confirmed COVID-19 disease compared to a control group of SARS-CoV-2 negative patients. We followed a cohort of 8786 non-hospitalized patients who were invited after SARS-CoV-2 testing between February 1 and April 15, 2020 (794 positive, 7229 negative). Participants answered online surveys at baseline and follow-up including questions on demographics, symptoms, risk factors for SARS-CoV-2, and self-rated health compared to one year ago. Determinants for a worsening of self-rated health as compared to one year ago among the SARS-CoV-2 positive group were analyzed using multivariate logistic regression and also compared to the population norm. The follow-up questionnaire was completed by 85% of the SARS-CoV-2 positive and 75% of the SARS-CoV-2 negative participants on average 132 days after the SARS-CoV-2 test. At follow-up, 36% of the SARS-CoV-2 positive participants rated their health "somewhat" or "much" worse than one year ago. In contrast, 18% of the SARS-CoV-2 negative participants reported a similar deterioration of health while the population norm is 12%. Sore throat and cough were more frequently reported by the control group at follow-up. Neither gender nor follow-up time was associated with the multivariate odds of worsening of self-reported health compared to one year ago. Age had an inverted-U formed association with a worsening of health while being fit and being a health professional were associated with lower multivariate odds. A significant proportion of non-hospitalized COVID-19 patients, regardless of age, have not returned to their usual health three to eight months after infection.}, } @article {pmid34436783, year = {2022}, author = {Catalán, IP and Martí, CR and Sota, DP and Álvarez, AC and Gimeno, MJE and Juana, SF and Rodríguez, GH and Bajo, ED and Gaya, NT and Blasco, JU and Rincón, JMR}, title = {Corticosteroids for COVID-19 symptoms and quality of life at 1 year from admission.}, journal = {Journal of medical virology}, volume = {94}, number = {1}, pages = {205-210}, pmid = {34436783}, issn = {1096-9071}, mesh = {Adrenal Cortex Hormones/*therapeutic use ; Aged ; COVID-19/complications/physiopathology/prevention & control ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; *Quality of Life ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {The long-term evolution of COVID-19 is unknown, making it necessary to study the persistence of symptoms over time and their impact on quality of life in people who have had the disease. We analyzed these aspects 1 year after admission for COVID-19 and explored the influence of treatment with systemic corticosteroids during the acute phase of the illness. This observational cohort study took place in a tertiary hospital in March and April 2021 and included people admitted due to infection with SARS-CoV-2 in March, April, or May 2020. We excluded patients who had died, were unreachable or had substantial cognitive impairment. A telephone survey was undertaken to assess the presence of symptoms related to COVID-19 and to administer the SF-36 quality of life questionnaire. Other variables collected were demographic and clinical data along with the treatment received and the evolution over time. We analyzed 76 patients, including 44 who did not receive corticosteroids and 32 who did. Most symptoms were less frequent in the group that received corticosteroids, with statistically significant differences for headache, dysphagia, chest pain, and depression. These patients also showed significantly better outcomes in the SF-36 domains for "bodily pain" and "mental health." Corticosteroids administered in the acute phase of COVID-19 could attenuate the presence of long-term symptoms and improve patients' quality of life.}, } @article {pmid34435313, year = {2022}, author = {Boehm, A and Luger, AK and Schmitz, K and Cima, K and Patscheider, DH and Augustin, F and Jakob, LM and Obermayer, A and Weiss, G and Stoiber, W and Widmann, G and Loeffler-Ragg, J}, title = {A spark of hope: histopathological and functional recovery after critical COVID-19.}, journal = {Infection}, volume = {50}, number = {1}, pages = {263-267}, pmid = {34435313}, issn = {1439-0973}, mesh = {Aged ; *COVID-19 ; Humans ; Lung ; Male ; Respiration, Artificial ; *Respiratory Distress Syndrome ; SARS-CoV-2 ; }, abstract = {BACKGROUND: There are substantial concerns about fibrotic and vascular pulmonary sequelae after coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).AQ1 Histopathology reports of lung biopsies from COVID-19 survivors are scarce.

CASE: We herein report results of functional and histopathological studies in a 70 year-old man undergoing a co-incidental tumor lobectomy six months after long-term mechanical ventilation for COVID-19 pneumonia.

CONCLUSION: Despite several unfavorable risk factors, this case presentation shows a completed pulmonary recovery process within a few months.}, } @article {pmid34428463, year = {2022}, author = {Gaffney, AW}, title = {The Long COVID Conundrum.}, journal = {The American journal of medicine}, volume = {135}, number = {1}, pages = {5-6}, pmid = {34428463}, issn = {1555-7162}, mesh = {COVID-19/*complications/epidemiology/therapy ; Humans ; Prevalence ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34426096, year = {2021}, author = {Mumoli, N and Conte, G and Evangelista, I and Cei, M and Mazzone, A and Colombo, A}, title = {Post-COVID or long-COVID: Two different conditions or the same?.}, journal = {Journal of infection and public health}, volume = {14}, number = {10}, pages = {1349-1350}, pmid = {34426096}, issn = {1876-035X}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34425843, year = {2021}, author = {Pretorius, E and Vlok, M and Venter, C and Bezuidenhout, JA and Laubscher, GJ and Steenkamp, J and Kell, DB}, title = {Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin.}, journal = {Cardiovascular diabetology}, volume = {20}, number = {1}, pages = {172}, pmid = {34425843}, issn = {1475-2840}, support = {NNF20CC0035580//novo nordisk foundation center for basic metabolic research/ ; }, mesh = {Adult ; Antifibrinolytic Agents/*metabolism ; Blood Coagulation Factors/*metabolism ; COVID-19/*complications ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis.

METHODS: We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms.

RESULTS: We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits.

CONCLUSIONS: Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.}, } @article {pmid34425627, year = {2021}, author = {August, D and Stete, K and Hilger, H and Götz, V and Biever, P and Hosp, J and Wagner, D and Köhler, TC and Gerstacker, K and Seufert, J and Laubner, K and Kern, W and Rieg, S}, title = {[Complaints and clinical findings six months after COVID-19: outpatient follow-up at the University Medical Center Freiburg].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {17}, pages = {e65-e73}, doi = {10.1055/a-1546-4291}, pmid = {34425627}, issn = {1439-4413}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anosmia ; Antibodies, Viral/blood ; COVID-19/*complications/epidemiology ; Dyspnea ; Fatigue ; Female ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; SARS-CoV-2/*immunology ; Sleep Initiation and Maintenance Disorders ; Surveys and Questionnaires ; Taste Disorders ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19. However, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg.

METHODS:  Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19. All patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists.

FINDINGS:  132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60 %) had been treated as outpatients and 53 (40 %) as inpatients. Most common complaints were persistent fatigue (82 %) and dyspnea on exertion (61 %). Further common complaints were impairments of concentration (54 %), insomnia (43 %), and impairments of smell or taste (35 %). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients.

CONCLUSION:  Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.}, } @article {pmid34425522, year = {2021}, author = {Rushforth, A and Ladds, E and Wieringa, S and Taylor, S and Husain, L and Greenhalgh, T}, title = {Long Covid - The illness narratives.}, journal = {Social science & medicine (1982)}, volume = {286}, number = {}, pages = {114326}, doi = {10.1016/j.socscimed.2021.114326}, pmid = {34425522}, issn = {1873-5347}, support = {WT104830MA/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*COVID-19/complications ; Communication ; Humans ; Narration ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Callard and Perego depict long Covid as the first illness to be defined by patients who came together on social media. Responding to their call to address why patients were so effective in making long Covid visible and igniting action to improve its care, we use narrative inquiry - a field of research that investigates the place and power of stories and storytelling. We analyse a large dataset of narrative interviews and focus groups with 114 people with long Covid (45 of whom were healthcare professionals) from the United Kingdom, drawing on socio-narratology (Frank), therapeutic emplotment (Mattingly) and polyphonia (Bakhtin). We describe how storytelling devices including chronology, metaphor, characterisation, suspense and imagination were used to create persuasive accounts of a strange and frightening new condition that was beset with setbacks and overlooked or dismissed by health professionals. The most unique feature of long Covid narratives (in most but not all cases) was the absence, for various pandemic-related reasons, of a professional witness to them. Instead of sharing their narratives in therapeutic dialogue with their own clinician, people struggled with a fragmented inner monologue before finding an empathetic audience and other resonant narratives in the online community. Individually, the stories seemed to make little sense. Collectively, they provided a rich description of the diverse manifestations of a grave new illness, a shared account of rejection by the healthcare system, and a powerful call for action to fix the broken story. Evolving from individual narrative postings to collective narrative drama, long Covid communities challenged the prevailing model of Covid-19 as a short-lived respiratory illness which invariably delivers a classic triad of symptoms; undertook and published peer-reviewed research to substantiate its diverse and protracted manifestations; and gained positions as experts by experience on guideline development groups and policy taskforces.}, } @article {pmid34419773, year = {2021}, author = {Montanari, M and Canonico, B and Nordi, E and Vandini, D and Barocci, S and Benedetti, S and Carlotti, E and Zamai, L}, title = {Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?.}, journal = {Advances in biological regulation}, volume = {81}, number = {}, pages = {100820}, pmid = {34419773}, issn = {2212-4934}, mesh = {ADAM17 Protein/antagonists & inhibitors/*biosynthesis ; Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors/*biosynthesis ; COVID-19/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Peptide Fragments/metabolism ; *Renin-Angiotensin System ; SARS-CoV-2/*metabolism ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors/*metabolism ; Up-Regulation ; COVID-19 Drug Treatment ; }, abstract = {The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.}, } @article {pmid34417203, year = {2021}, author = {McCartney, M and Byng, R}, title = {Long covid clinics should be run as research hubs.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1996}, doi = {10.1136/bmj.n1996}, pmid = {34417203}, issn = {1756-1833}, mesh = {Ambulatory Care Facilities/*organization & administration ; COVID-19/*complications/therapy/virology ; England ; Humans ; Interdisciplinary Research/*methods ; Research Design ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34416191, year = {2021}, author = {Adeloye, D and Elneima, O and Daines, L and Poinasamy, K and Quint, JK and Walker, S and Brightling, CE and Siddiqui, S and Hurst, JR and Chalmers, JD and Pfeffer, PE and Novotny, P and Drake, TM and Heaney, LG and Rudan, I and Sheikh, A and De Soyza, A and , }, title = {The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {12}, pages = {1467-1478}, pmid = {34416191}, issn = {2213-2619}, support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MC_PC_19075/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications ; Consensus ; Humans ; Research ; *Respiration Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.}, } @article {pmid34416190, year = {2021}, author = {Beasley, R and Kearns, N and Hills, T}, title = {Charting a course for the management of long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {12}, pages = {1358-1360}, pmid = {34416190}, issn = {2213-2619}, mesh = {*COVID-19/complications ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34414665, year = {2021}, author = {Basic-Jukic, N and Juric, I and Furic-Cunko, V and Katalinic, L and Radic, J and Bosnjak, Z and Jelakovic, B and Kastelan, Z}, title = {Follow-up of renal transplant recipients after acute COVID-19-A prospective cohort single-center study.}, journal = {Immunity, inflammation and disease}, volume = {9}, number = {4}, pages = {1563-1572}, pmid = {34414665}, issn = {2050-4527}, mesh = {*COVID-19 ; Cohort Studies ; *Epstein-Barr Virus Infections ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; *Kidney Transplantation/adverse effects ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Although most patients recover within several weeks after acute COVID-19, some of them develop long-lasting clinical symptoms. Renal transplant recipients have an increased mortality risk from COVID-19. We aimed to describe complications occurring after COVID-19 in this group of patients.

METHODS: A prospective single-center cohort study was conducted at University Hospital Centre Zagreb. Patients with two negative reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 after COVID-19 were eligible for further follow-up at our outpatient clinic. They underwent detailed clinical and laboratory assessments. The primary outcome was the development of complications after COVID-19.

RESULTS: Only 11.53% of renal transplant recipients who survived acute COVID-19 were symptomless and free from new-onset laboratory abnormalities during the median follow-up of 64 days (range: 50-76 days). Three patients died from sepsis after discharge from the hospital. In 47 patients (45.2%), clinical complications were present, while 74 patients (71.2%) had one or more laboratory abnormalities. The most common clinical complications included shortness of breath (19.2%), tiredness (11.5%), peripheral neuropathy (7.7%), self-reported cognitive impairments (5.7%), and dry cough (7.7%). Most common laboratory abnormalities included shortened activated partial thromboplastin time (50%), elevated D-dimers (36.5%), elevated fibrinogen (30.16%), and hypogammaglobulinemia (24%). Positive RT-PCR for cytomegalovirus (8.7%), Epstein-Barr virus (26%), or BK virus (16.3%). Multivariate analysis identified the history of diabetes mellitus and eGFR CKD-EPI as predictors for the development of post-COVID clinical complications. Six months after acute COVID-19, elevated D-dimers persisted with normalization of other laboratory parameters. Twenty-nine patients were hospitalized, mostly with several concomitant problems. However, initially reported clinical problems gradually improved in the majority of patients.

CONCLUSION: Post-COVID-19 clinical and laboratory complications are frequent in the renal transplant population, in some of them associated with significant morbidity. All patients recovered from acute COVID-19 should undergo long-term monitoring for evaluation and treatment of complications.}, } @article {pmid34414470, year = {2022}, author = {Morand, A and Campion, JY and Lepine, A and Bosdure, E and Luciani, L and Cammilleri, S and Chabrol, B and Guedj, E}, title = {Similar patterns of [[18]F]-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {49}, number = {3}, pages = {913-920}, pmid = {34414470}, issn = {1619-7089}, support = {PHRC 07 09//aphm/ ; }, mesh = {Brain/diagnostic imaging ; *COVID-19/complications ; Child ; Fluorodeoxyglucose F18 ; Humans ; Positron-Emission Tomography ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical presentation has been referred as "long COVID" in the adult population, and an [[18]F]-FDG brain PET hypometabolic pattern has recently been suggested as a biomarker. Herein, we present a retrospective analysis of 7 paediatric patients with suspected long COVID who were explored by [[18]F]-FDG brain PET exam. Metabolic brain findings were confronted to those obtained in adult patients with long COVID, in comparison to their respective age-matched control groups.

METHODS: Review of clinical examination and whole-brain voxel-based analysis of [[18]F]-FDG PET metabolism of the 7 children in comparison to 21 paediatric controls, 35 adult patients with long COVID and 44 healthy adult subjects.

RESULTS: Despite lower initial severity at the acute stage of the infection, paediatric patients demonstrated on average 5 months later a similar brain hypometabolic pattern as that found in adult long COVID patients, involving bilateral medial temporal lobes, brainstem and cerebellum (p-voxel < 0.001, p-cluster < 0.05 FWE-corrected), and also the right olfactory gyrus after small volume correction (p-voxel = 0.010 FWE-corrected), with partial PET recovery in two children at follow-up.

CONCLUSION: These results provide arguments in favour of possible long COVID in children, with a similar functional brain involvement to those found in adults, regardless of age and initial severity.}, } @article {pmid34408742, year = {2021}, author = {O'Donnell, JS and Chappell, KJ}, title = {Chronic SARS-CoV-2, a Cause of Post-acute COVID-19 Sequelae (Long-COVID)?.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {724654}, pmid = {34408742}, issn = {1664-302X}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause coronavirus disease 2019 (COVID-19). Most individuals recover from SARS-CoV-2 infection, however, many continue to experience a cluster of persistent symptoms for months following resolution of acute disease; a syndrome that has been named Long-COVID. While the biological cause, or causes, of Long-COVID have not yet been confirmed, the main proposals have centred around either virus-induced autoimmunity or virus-induced tissue dysfunction. However, an alternative suggestion that a latent chronic infection could be responsible for the symptoms of Long-COVID has received minimal attention despite recent findings that SARS-CoV-2 genetic material and infections are detected in some individuals months following resolution of respiratory disease. Here we discuss literature supporting the possibility that Long-COVID occurs as a result of chronic SARS-CoV-2 infections.}, } @article {pmid34408531, year = {2021}, author = {Jones, R and Davis, A and Stanley, B and Julious, S and Ryan, D and Jackson, DJ and Halpin, DMG and Hickman, K and Pinnock, H and Quint, JK and Khunti, K and Heaney, LG and Oliver, P and Siddiqui, S and Pavord, I and Jones, DHM and Hyland, M and Ritchie, L and Young, P and Megaw, T and Davis, S and Walker, S and Holgate, S and Beecroft, S and Kemppinen, A and Appiagyei, F and Roberts, EJ and Preston, M and Hardjojo, A and Carter, V and van Melle, M and Price, D}, title = {Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients.}, journal = {Pragmatic and observational research}, volume = {12}, number = {}, pages = {93-104}, pmid = {34408531}, issn = {1179-7266}, support = {G0800766/MRC_/Medical Research Council/United Kingdom ; }, abstract = {INTRODUCTION: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care.

METHODS: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18-85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration.

RESULTS: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05-2.17]), female sex (adjOR=1.37 [1.02-1.85]), frailty (adjOR=2.39 [1.29-4.27]), visit to A&E (adjOR=4.28 [2.31-7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77-5.79]). Aches and pain (adjOR=1.70 [1.21-2.39]), appetite loss (adjOR=3.15 [1.78-5.92]), confusion and disorientation (adjOR=2.17 [1.57-2.99]), diarrhea (adjOR=1.4 [1.03-1.89]), and persistent dry cough (adjOR=2.77 [1.94-3.98]) were symptom features statistically more common in long COVID.

CONCLUSION: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.}, } @article {pmid34407902, year = {2022}, author = {Erol, N and Alpinar, A and Erol, C and Sari, E and Alkan, K}, title = {Intriguing new faces of Covid-19: persisting clinical symptoms and cardiac effects in children.}, journal = {Cardiology in the young}, volume = {32}, number = {7}, pages = {1085-1091}, pmid = {34407902}, issn = {1467-1107}, mesh = {Adolescent ; *COVID-19/complications ; Child ; Child, Preschool ; Echocardiography ; Humans ; Infant ; Infant, Newborn ; Stroke Volume ; Ventricular Function, Left ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: This study was conducted to evaluate the persisting Covid-19-related symptoms of the cases included in our study and to assess their cardiac findings to determine the impact of Covid-19 on children's cardiovascular health.

METHODS: In this study, 121 children between the ages of 0- and 18 with Covid-19 were evaluated based on their history, blood pressure values, and electrocardiography and echocardiography results. These findings were compared with the findings of the control group which consisted of 95 healthy cases who were in the same age range as the study group and did not have Covid-19. The results were evaluated using the statistics program, SPSS 21.

RESULTS: There was no significant difference between the study group and the control group in terms of age, weight, and body mass index. The clinical symptoms (chest and back pain, dizziness, headache, palpitation, fatigue, shortness of breath, loss of balance, coughing) of 37.2% of the cases persisted for at least 1 month after Covid-19 recovery. Statistically significant differences were found in systolic blood pressure, left ventricular ejection fraction, relative wall thickness, and tricuspid annular plane systolic excursion.

CONCLUSION: The continuation of some cases' clinical symptoms post-recovery indicates that long Covid infection can be observed in children. The fact that statistically significant differences were observed between the echocardiographic parameters of the study and control groups suggests that Covid-19 may have effects on the cardiovascular system. To shed light on the long Covid cases among children and the infection's cardiac impacts, it would be beneficial to conduct more comprehensive studies on this matter.}, } @article {pmid34405799, year = {2021}, author = {Wilcox, J and Frank, E}, title = {Occupational Therapy for the Long Haul of Post-COVID Syndrome: A Case Report.}, journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}, volume = {75}, number = {Supplement_1}, pages = {7511210060p1-7511210060p7}, doi = {10.5014/ajot.2021.049223}, pmid = {34405799}, issn = {0272-9490}, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; *Occupational Therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Prolonged symptoms from the novel coronavirus disease 2019 (COVID-19), otherwise known as long COVID, postacute sequelae of COVID-19 (PASC), or post-COVID syndrome, are affecting an increasingly high number of patients after severe, moderate, and mild acute COVID-19 infections. Using evidence-based practice strategies, this case report describes occupational therapy evaluation and treatment approaches, plan of care, and associated outcomes for one client experiencing long COVID symptoms in the outpatient setting.}, } @article {pmid34403368, year = {2021}, author = {Haran, JP and Bradley, E and Zeamer, AL and Cincotta, L and Salive, MC and Dutta, P and Mutaawe, S and Anya, O and Meza-Segura, M and Moormann, AM and Ward, DV and McCormick, BA and Bucci, V}, title = {Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID.}, journal = {JCI insight}, volume = {6}, number = {20}, pages = {}, pmid = {34403368}, issn = {2379-3708}, support = {RF1 AG067483/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Bacteria/classification ; COVID-19/*complications ; *Dysbiosis ; Female ; Gastrointestinal Microbiome ; Humans ; *Inflammation ; Male ; *Microbiota ; Middle Aged ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {In the COVID-19 pandemic, caused by SARS-CoV-2, many individuals experience prolonged symptoms, termed long-lasting COVID-19 symptoms (long COVID). Long COVID is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the role of the microbiome in mediating inflammation, we aimed to examine the relationship between the oral microbiome and the duration of long COVID symptoms. Tongue swabs were collected from patients presenting with COVID-19 symptoms. Confirmed infections were followed until resolution of all symptoms. Bacterial composition was determined by metagenomic sequencing. We used random forest modeling to identify microbiota and clinical covariates that are associated with long COVID symptoms. Of the patients followed, 63% developed ongoing symptomatic COVID-19 and 37% went on to long COVID. Patients with prolonged symptoms had significantly higher abundances of microbiota that induced inflammation, such as members of the genera Prevotella and Veillonella, which, of note, are species that produce LPS. The oral microbiome of patients with long COVID was similar to that of patients with chronic fatigue syndrome. Altogether, our findings suggest an association with the oral microbiome and long COVID, revealing the possibility that dysfunction of the oral microbiome may have contributed to this draining disease.}, } @article {pmid34401886, year = {2022}, author = {Visvabharathy, L and Hanson, BA and Orban, ZS and Lim, PH and Palacio, NM and Jimenez, M and Clark, JR and Graham, EL and Liotta, EM and Tachas, G and Penaloza-MacMaster, P and Koralnik, IJ}, title = {T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {34401886}, support = {L30 NS098427/NS/NINDS NIH HHS/United States ; DP2 DA051912/DA/NIDA NIH HHS/United States ; U54 EB027049/EB/NIBIB NIH HHS/United States ; T32 AR007611/AR/NIAMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; }, abstract = {Many people experiencing long COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). However, whether virus-specific adaptive immunity is affected in Neuro-PASC patients remains poorly understood. We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated humoral and cellular responses toward SARS-CoV-2 Nucleocapsid protein at an average of 6 months post-infection compared to healthy COVID convalescents. Neuro-PASC patients also had enhanced virus-specific production of IL-6 from and diminished activation of CD8[+] T cells. Furthermore, the severity of cognitive deficits or quality of life disturbances in Neuro-PASC patients were associated with a reduced diversity of effector molecule expression in T cells but elevated IFN-γ production to the C-terminal domain of Nucleocapsid protein. Proteomics analysis showed enhanced plasma immunoregulatory proteins and reduced pro-inflammatory and antiviral response proteins in Neuro-PASC patients compared with healthy COVID convalescents, which were also correlated with worse neurocognitive dysfunction. These data provide new insight into the pathogenesis of long COVID syndrome and a framework for the rational design of predictive biomarkers and therapeutic interventions.}, } @article {pmid34400495, year = {2021}, author = {Paul, BD and Lemle, MD and Komaroff, AL and Snyder, SH}, title = {Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {34}, pages = {}, pmid = {34400495}, issn = {1091-6490}, support = {5U54 AI138370/NH/NIH HHS/United States ; DA044123/NH/NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; /AHA/American Heart Association-American Stroke Association/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; COVID-19/complications/etiology/immunology/*metabolism ; Encephalomyelitis/immunology/*metabolism ; Fatigue Syndrome, Chronic/immunology/*metabolism ; Humans ; Oxidation-Reduction ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called "long COVID-19," reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.}, } @article {pmid34400406, year = {2021}, author = {Watterson, A}, title = {Failure to prescribe: UK workers with occupational long covid-19 have been ignored.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n2018}, doi = {10.1136/bmj.n2018}, pmid = {34400406}, issn = {1756-1833}, mesh = {COVID-19/*complications/*epidemiology/virology ; Health Personnel/*statistics & numerical data ; Humans ; Occupational Diseases/*epidemiology/virology ; Occupational Exposure/adverse effects ; Occupational Health/legislation & jurisprudence/*trends ; SARS-CoV-2 ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34396514, year = {2021}, author = {Wagner, C and Griesel, M and Mikolajewska, A and Mueller, A and Nothacker, M and Kley, K and Metzendorf, MI and Fischer, AL and Kopp, M and Stegemann, M and Skoetz, N and Fichtner, F}, title = {Systemic corticosteroids for the treatment of COVID-19.}, journal = {The Cochrane database of systematic reviews}, volume = {8}, number = {8}, pages = {CD014963}, pmid = {34396514}, issn = {1469-493X}, mesh = {Adrenal Cortex Hormones/*therapeutic use ; COVID-19/diagnosis ; Humans ; Immunization, Passive ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.

OBJECTIVES: To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID-19, and to keep up to date with the evolving evidence base using a living systematic review approach.

SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity.  We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances.  We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation, quality of life, serious adverse events, adverse events, and hospital-acquired infections.

MAIN RESULTS: We included 11 RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet.  Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo  We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies.  All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence).  Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution.  New need for invasive ventilation: the evidence is of very low certainty. Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics.  Quality of life/neurological outcome: no data were available. Serious adverse events: we included data on two RCTs (678 participants) that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants). Because of high risk of bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence).    Different types, dosages or timing of systemic corticosteroids  We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.

AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to  adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants).  There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable.  We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.}, } @article {pmid34391037, year = {2021}, author = {Jesuthasan, A and Massey, F and Manji, H and Zandi, MS and Wiethoff, S}, title = {Emerging potential mechanisms and predispositions to the neurological manifestations of COVID-19.}, journal = {Journal of the neurological sciences}, volume = {428}, number = {}, pages = {117608}, pmid = {34391037}, issn = {1878-5883}, mesh = {*COVID-19/complications ; Cytokine Release Syndrome ; Humans ; *Nervous System Diseases/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {A spectrum of neurological disease associated with COVID-19 is becoming increasingly apparent. However, the mechanisms behind these manifestations remain poorly understood, significantly hindering their management. The present review subsequently attempts to address the evolving molecular, cellular and systemic mechanisms of NeuroCOVID, which we have classified as the acute and long-term neurological effects of COVID-19. We place particular emphasis on cerebrovascular, demyelinating and encephalitic presentations, which have been reported. Several mechanisms are presented, especially the involvement of a "cytokine storm". We explore the genetic and demographic factors that may predispose individuals to NeuroCOVID. The increasingly evident long-term neurological effects are also presented, including the impact of the virus on cognition, autonomic function and mental wellbeing, which represent an impending burden on already stretched healthcare services. We subsequently reinforce the need for cautious surveillance, especially for those with predisposing factors, with effective clinical phenotyping, appropriate investigation and, if possible, prompt treatment. This will be imperative to prevent downstream neurological sequelae, including those related to the long COVID phenotypes that are being increasingly recognised.}, } @article {pmid34390552, year = {2021}, author = {Economou, M}, title = {Social Distance in COVID-19: Drawing the line between protective behavior and stigma manifestation.}, journal = {Psychiatrike = Psychiatriki}, volume = {32}, number = {3}, pages = {183-186}, doi = {10.22365/jpsych.2021.025}, pmid = {34390552}, issn = {1105-2333}, mesh = {*COVID-19/complications/epidemiology/prevention & control/psychology/transmission ; Communicable Disease Control/methods ; Disease Transmission, Infectious/prevention & control ; Greece/epidemiology ; Humans ; *Mental Disorders/epidemiology/physiopathology ; *Physical Distancing ; *Psychological Distance ; *Psychological Distress ; Psychosocial Intervention/*methods ; SARS-CoV-2 ; Social Discrimination/prevention & control/psychology ; Social Isolation/psychology ; *Social Stigma ; Time-to-Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {Social stigma has long been defined by Ervin Goffman as an attribute that it is deeply discrediting and reduces the individual who bears it from a whole and usual person to a tarnished one, unfit to be included into the mainstream society.1 As stigma spans time and space and has been documented in other social species such as ants and chimpanzees, one might argue for its adaptive potential. Neuberg and colleagues2 have suggested that humans generate stigmas against threats to effective group functioning, with a notable case being infectious diseases. A similar explanation has been put forward by other researchers who consider stigma to have evolved from disease-avoidance mechanisms.3 Hence, it is not surprising that tuberculosis, HIV and leprosy have been surrounded by stigma and discrimination.4,5 More recently, people who had survived the 2013-2016 Ebola outbreak tackled social exclusion and unemployment after returning to their neighborhoods.6 Nowadays, the global community faces an unprecedented challenge of grappling with the COVID-19 pandemic. From the very outset, social distance measures were introduced in order to contain the spread of the virus, ranging from maintaining 1.5 meters physical distance to strict lockdowns. However, this may easily escalate into stigmatizing and discriminatory behaviours (desired social distance is a proxy of discrimination) against people who have suffered from COVID-19, their relatives and their caregivers, with the United Nations stating that "fear, rumours and stigma" are the key challenges surrounding COVID-19.7 Apart from the psychological distress experienced by the stigmatized individuals, due to anticipated stigma people might start concealing their illness, avoid or delay seeking medical advice or testing until they are seriously ill and be reluctant to collaborate with authorities on tracing contacts. Therefore, timely identifying stigma and addressing it is an integral part of an effective health response to the ongoing pandemic. In spite of its importance, research on COVID-19 related stigma is scarce. From the perspective of the stigmatized individuals, a study in China8 demonstrated that COVID-19 survivors faced heightened levels of overall stigma, social rejection, financial insecurity, internalized shame and social isolation, compared to healthy controls. From the perspective of the general population, a study in US9 substantiated low levels of anticipated stigma and stereotype endorsement; however, respondents who anticipated greater stigma were less likely to seek a COVID-19 test. It is therefore clear that the international literature is still on its infancy with respect to COVID-19 related stigma. In this context, in the First Department of Psychiatry, University of Athens, we conducted a survey on public attitudes to COVID-19 and to mental disorders. The study would inform the design and implementation of anti-stigma initiatives, funded by the Regional Governor of Attica. As physical distancing and social distancing are interwoven, with some researchers and practitioners using the terms interchangeably, and social distancing is also a protective public health measure against COVID-19, we enquired about attitudes and desired social distance from people who had recovered from COVID-19. Nonetheless, it merits noting that evidence from other diseases indicates that stigma may persist even after recovery.10 Moreover, rather than describing public attitudes overall, we were more interested in investigating where COVID-19 related stigma stands as compared to the most stigmatizing health condition to date, i.e., severe mental illness.11 Interestingly enough, which elements of severe mental illness render it the most stigmatized as compared to other conditions is still speculative: is it the fear of madness? the severity and the type of symptoms? the purported incurability or its chronicity? In our study, evidence from a convenience sample of 370 residents of Attica indicates that the general population holds more negative attitudes towards people who have recovered from COVID-19 than towards people with mental disorders. Nonetheless, respondents reported lower levels of desired social distance from recovered COVID-19 cases as compared to mental illness cases in social interactions of graded intimacy; however, the difference between the two groups was found to decrease as the level of intimacy decreased as well. In other words, desired social distance from COVID-19 cases is more easily discernible in transient social encounters, like talking to a stranger. It is therefore clear that social distance is still a public health protective measure rather than a stigma manifestation. For social encounters of greater intimacy, usually a sign of discriminatory behaviours, having recovered from COVID-19 is not a deterrent to interaction. Findings can be explained by the acute (non-chronic) nature of the disease, both in terms of symptoms as well as the 10-day period since symptom onset for being contagious. Nonetheless, with emerging evidence substantiating the notion of long COVID-19, defined as the persistence of symptoms for 3 weeks after infection,12 this might quickly change. Moreover, with many public health protective measures available, such as the use of mask, diagnostic testing and vaccination, people who become infected are more likely to be blamed for contracting the disease and thus deemed responsible for this, in line with the Attribution Theory.13 Specifically, overarching evidence from stigma research in many diseases/conditions indicates that when an illness or a social condition, such as economic disadvantage, is attributed to internal causes, as compared to external, lay people are more likely to hold stigmatizing attitudes.14-16 Therefore, as attitudes towards COVID-19 are worse compared to those towards people with mental illness, if tailored anti-stigma action is not undertaken, it is only a matter of time for prejudices to evolve into discriminatory behaviours, with devastating consequences on both the individuals and the course of the pandemic. Concomitantly, as severe mental illness is neither life threatening nor contagious, but COVID-19 is, it is interesting to explore how stigma is related to evolutionary mechanisms favouring adaptability and survival as well as which elements are the drivers of stigma development and establishment. Therefore, comparing and contrasting the stigma surrounding these conditions may shed light on the underpinnings of social stigma and facilitate effective interventions to reduce it and eventually eliminate it.}, } @article {pmid34386903, year = {2022}, author = {Buoite Stella, A and Furlanis, G and Frezza, NA and Valentinotti, R and Ajcevic, M and Manganotti, P}, title = {Autonomic dysfunction in post-COVID patients with and witfhout neurological symptoms: a prospective multidomain observational study.}, journal = {Journal of neurology}, volume = {269}, number = {2}, pages = {587-596}, pmid = {34386903}, issn = {1432-1459}, mesh = {*Autonomic Nervous System Diseases/diagnosis/etiology ; *COVID-19 ; Female ; Humans ; *Hypotension, Orthostatic ; Male ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {The autonomic nervous system (ANS) can be affected by COVID-19, and dysautonomia may be a possible complication in post-COVID individuals. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been suggested to be common after SARS-CoV-2 infection, but other components of ANS function may be also impaired. The Composite Autonomic Symptom Scale 31 (COMPASS-31) questionnaire is a simple and validated tool to assess dysautonomic symptoms. The aim of the present study was to administer the COMPASS-31 questionnaire to a sample of post-COVID patients with and without neurological complaints. Participants were recruited among the post-COVID ambulatory services for follow-up evaluation between 4 weeks and 9 months from COVID-19 symptoms onset. Participants were asked to complete the COMPASS-31 questionnaire referring to the period after COVID-19 disease. Heart rate and blood pressure were manually taken during an active stand test for OH and POTS diagnosis. One-hundred and eighty participants were included in the analysis (70.6% females, 51 ± 13 years), and OH was found in 13.8% of the subjects. Median COMPASS-31 score was 17.6 (6.9-31.4), with the most affected domains being orthostatic intolerance, sudomotor, gastrointestinal and pupillomotor dysfunction. A higher COMPASS-31 score was found in those with neurological symptoms (p < 0.01), due to more severe orthostatic intolerance symptoms (p < 0.01), although gastrointestinal (p < 0.01), urinary (p < 0.01), and pupillomotor (p < 0.01) domains were more represented in the non-neurological symptoms group. This study confirms the importance of monitoring ANS symptoms as a possible complication of COVID-19 disease that may persist in the post-acute period.}, } @article {pmid34386785, year = {2021}, author = {Sigfrid, L and Drake, TM and Pauley, E and Jesudason, EC and Olliaro, P and Lim, WS and Gillesen, A and Berry, C and Lowe, DJ and McPeake, J and Lone, N and Munblit, D and Cevik, M and Casey, A and Bannister, P and Russell, CD and Goodwin, L and Ho, A and Turtle, L and O'Hara, ME and Hastie, C and Donohue, C and Spencer, RG and Donegan, C and Gummery, A and Harrison, J and Hardwick, HE and Hastie, CE and Carson, G and Merson, L and Baillie, JK and Openshaw, P and Harrison, EM and Docherty, AB and Semple, MG and Scott, JT and , }, title = {Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.}, journal = {The Lancet regional health. Europe}, volume = {8}, number = {}, pages = {100186}, pmid = {34386785}, issn = {2666-7762}, support = {MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/9/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; MC_PC_19025/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MC_PC_15001/MRC_/Medical Research Council/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MR/N003403/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: This study sought to establish the long-term effects of Covid-19 following hospitalisation.

METHODS: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).

FINDINGS: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.

INTERPRETATION: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.

FUNDING: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.}, } @article {pmid34386546, year = {2021}, author = {Lombardo, MDM and Foppiani, A and Peretti, GM and Mangiavini, L and Battezzati, A and Bertoli, S and Martinelli Boneschi, F and Zuccotti, GV}, title = {Long-Term Coronavirus Disease 2019 Complications in Inpatients and Outpatients: A One-Year Follow-up Cohort Study.}, journal = {Open forum infectious diseases}, volume = {8}, number = {8}, pages = {ofab384}, pmid = {34386546}, issn = {2328-8957}, abstract = {BACKGROUND: As the coronavirus pandemic spreads, more and more people are infected with severe acute respiratory syndrome coronavirus 2. The short- and medium-term effects of the infection have been described, but the description of the long-term sequelae is lacking in the literature.

METHODS: Patients healed from coronavirus disease 2019 (COVID-19) from February 2020 to May 2020 were considered for inclusion in this study, regardless of the severity of the disease during the acute phase. Eligible patients were consecutively contacted and a semistructured interview was administered between February and March 2021 by trained medical staff.

RESULTS: Three hundred three patients were eligible and accepted to participate in the study and were enrolled. Of those surveyed, most patients (81%) reported at least 1 symptom, and the most prevalent symptoms were fatigue (52%), pain (48%), and sleep disorders (47%). Sensory alterations were present in 28% of surveyed patients, but in most of these cases (74% of those affected by sensory alterations or 20% of the overall sample) symptoms reported were either anosmia or dysgeusia. Higher prevalence was generally observed with increasing age, although the most relevant differences were observed when comparing young versus middle-aged adults.

CONCLUSIONS: At 12 months after acute infection, COVID-19 survivors were still suffering from symptoms identified at shorter follow-up, and the most frequent symptoms included fatigue, pain, and sleep disorders. A more severe impairment in the acute phase did not seem to predict more severe complications.}, } @article {pmid34384972, year = {2021}, author = {Raveendran, AV and Misra, A}, title = {Post COVID-19 Syndrome ("Long COVID") and Diabetes: Challenges in Diagnosis and Management.}, journal = {Diabetes & metabolic syndrome}, volume = {15}, number = {5}, pages = {102235}, pmid = {34384972}, issn = {1878-0334}, mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Comorbidity ; Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology/therapy ; Fatigue/diagnosis/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Sarcopenia/diagnosis/epidemiology/etiology/therapy ; Tachycardia/diagnosis/epidemiology/etiology/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND AIMS: Post Covid-19 syndrome (PCS) is a major cause of morbidity. In this article we intend to review the association and consequences of PCS and diabetes.

METHODS: We reviewed all studies on "Long Covid", "Post COVID-19 Syndrome" and diabetes in PubMed and Google Scholar.

RESULTS: The symptoms of PCS can be due to organ dysfunction, effects of hospitalisation and drugs, or unrelated to these. Type 2 diabetes mellitus has a bidirectional relationship with COVID-19. Presence of diabetes also influences PCS via various pathophysiological mechanisms. COVID-19 can add to or exacerbate tachycardia, sarcopenia (and muscle fatigue), and microvascular dysfunction (and organ damage) in patients with diabetes.

CONCLUSION: PCS in patients with diabetes could be detrimental in multiple ways. Strict control of diabetes and other comorbidities, supervised rehabilitation and physical exercise, and optimal nutrition could help in reducing and managing PCS.}, } @article {pmid34375505, year = {2021}, author = {Fogarty, H and Townsend, L and Morrin, H and Ahmad, A and Comerford, C and Karampini, E and Englert, H and Byrne, M and Bergin, C and O'Sullivan, JM and Martin-Loeches, I and Nadarajan, P and Bannan, C and Mallon, PW and Curley, GF and Preston, RJS and Rehill, AM and McGonagle, D and Ni Cheallaigh, C and Baker, RI and Renné, T and Ward, SE and O'Donnell, JS and , }, title = {Persistent endotheliopathy in the pathogenesis of long COVID syndrome.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {19}, number = {10}, pages = {2546-2553}, pmid = {34375505}, issn = {1538-7836}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Aged ; Biomarkers ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; von Willebrand Factor ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19.

OBJECTIVES: To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis.

PATIENTS AND METHODS: Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed.

RESULTS: Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI -2.57 to -1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15-416 nM/min), and peak thrombin (p < .0001, 95% CI 39-93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09-0.57 IU/ml; p = .009, 95% CI 0.06-0.5 IU/ml; p = .04, 95% CI 0.03-0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01-2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests.

CONCLUSIONS: Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.}, } @article {pmid34373540, year = {2021}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S}, title = {More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {16144}, pmid = {34373540}, issn = {2045-2322}, support = {R21 NS106640/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alopecia/complications/*diagnosis ; Attention Deficit Disorder with Hyperactivity/complications/*diagnosis ; COVID-19/*complications/virology ; Dyspnea/complications/*diagnosis ; Fatigue/complications/*diagnosis ; Headache/complications/*diagnosis ; Humans ; Middle Aged ; SARS-CoV-2/physiology ; Young Adult ; }, abstract = {COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17-87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.}, } @article {pmid34371940, year = {2021}, author = {Townsend, L and Dyer, AH and McCluskey, P and O'Brien, K and Dowds, J and Laird, E and Bannan, C and Bourke, NM and Ní Cheallaigh, C and Byrne, DG and Kenny, RA}, title = {Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection.}, journal = {Nutrients}, volume = {13}, number = {7}, pages = {}, pmid = {34371940}, issn = {2072-6643}, support = {203930/B/16/Z/WT_/Wellcome Trust/United Kingdom ; 203930/B/16/Z/HRBI_/Health Research Board/Ireland ; }, mesh = {Age Factors ; COVID-19/blood/*complications/etiology/pathology ; Fatigue/blood/etiology ; Female ; Humans ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Regression Analysis ; Risk Factors ; Sex Factors ; Time Factors ; Vitamin D/*blood ; Post-Acute COVID-19 Syndrome ; }, abstract = {The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30-49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.}, } @article {pmid34371507, year = {2021}, author = {Ashkenazi-Hoffnung, L and Shmueli, E and Ehrlich, S and Ziv, A and Bar-On, O and Birk, E and Lowenthal, A and Prais, D}, title = {Long COVID in Children: Observations From a Designated Pediatric Clinic.}, journal = {The Pediatric infectious disease journal}, volume = {40}, number = {12}, pages = {e509-e511}, pmid = {34371507}, issn = {1532-0987}, mesh = {Adolescent ; COVID-19/*complications/virology ; Child ; Female ; Humans ; Male ; Prospective Studies ; SARS-CoV-2/*pathogenicity ; Tertiary Care Centers/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {Systematic data are lacking on pediatric long COVID. This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID. In nearly 60%, symptoms were associated with functional impairment at 1-7 months after the onset of infection. A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients, mainly in the respiratory aspect.}, } @article {pmid34370958, year = {2023}, author = {Michel-Chávez, A and García-Grimshaw, M and Chávez-Martínez, OA and Cantú-Brito, C and Romero-Sánchez, GT and Flores-Silva, FD and Merayo-Chalico, FJ and Martínez-Carrillo, FM and Barrera-Vargas, A and Valdés-Ferrer, SI}, title = {Posterior reversible encephalopathy syndrome during convalescence from COVID-19.}, journal = {The International journal of neuroscience}, volume = {133}, number = {6}, pages = {672-675}, doi = {10.1080/00207454.2021.1966629}, pmid = {34370958}, issn = {1563-5279}, mesh = {Humans ; Female ; Middle Aged ; *COVID-19/complications ; SARS-CoV-2 ; *Posterior Leukoencephalopathy Syndrome/diagnostic imaging/etiology/pathology ; Convalescence ; Levetiracetam ; }, abstract = {Background and aim: With an ever-increasing population of patients recovering form severe coronavirus disease 2019 (COVID-19), recognizing long-standing and delayed neurologic manifestations is crucial. Here, we present a patient developing posterior reversible encephalopathy syndrome (PRES) in the convalescence form severe coronavirus disease 2019 (COVID-19).Case presentation: A 61-year-old woman with severe (COVID-19) confirmed by nasopharyngeal real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) required invasive mechanical ventilation 24-hours after admission. During her intensive care unit stay, she developed transient acute kidney injury and septic shock. She was extubated after 22 days. On day 25, she developed generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) of the brain showed bilateral subcortical lesions on the parietal and occipital lobes and multiple micro-and macro-bleeds, consistent with PRES. At this point, RT-PCR for SARS-CoV-2 in a respiratory specimen and cerebrospinal fluid was negative. She was discharged home 35 days after admission on oral levetiracetam. Control MRI five months after discharge showed bilateral focal gliosis. On follow-up, she remains seizure-free on levetiracetam.Conclusions: PRES has been observed before as a neurological manifestation of acute COVID-19; to our knowledge, this is the first PRES case occurring in a hospitalized patient already recovered from COVID-19. A persistent proinflammatory/prothrombotic state triggered by SARS-CoV-2 infection may lead to long-standing endothelial dysfunction, resulting in delayed PRES in patients recovering from COVID-19. With a rapid and exponential increase in survivors of acute COVID-19, clinicians should be aware of delayed (post-acute) neurological damage, including PRES.}, } @article {pmid34368201, year = {2021}, author = {Pasini, E and Corsetti, G and Romano, C and Scarabelli, TM and Chen-Scarabelli, C and Saravolatz, L and Dioguardi, FS}, title = {Serum Metabolic Profile in Patients With Long-Covid (PASC) Syndrome: Clinical Implications.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {714426}, pmid = {34368201}, issn = {2296-858X}, abstract = {Background: Many patients who have been suffering by Covid-19 suffer of long-Covid syndrome, with symptoms of fatigue and muscular weakness that characterize post-acute sequelae SARS-CoV-2 infection (PASC). However, there is limited knowledge about the molecular pathophysiology, and about the serum profile of these patients. Methods: We studied the blood serum profile of 75 selected patients, with previous confirmed Covid-19, 2 months after hospital discharge, who reported new-onset fatigue, muscle weakness and/or dyspnea not present prior to the virus infection and independently from concomitant diseases and/or clinical conditions. Results: All patients had very high serum concentrations of ferritin and D-Dimer. 87 and 72% of patients had clinically significant low levels of hemoglobin and albumin, respectively. Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP. Twenty seven percentage had elevations in LDH. Conclusions: The co-existence of patient symptoms along with blood markers of coagulation, protein disarrangement and inflammation suggests ongoing alterations in the metabolism, promoting an inflammatory/hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC. The persistence of altered D-Dimer levels raises the possibility of long-term risks of thromboembolic disease. All these markers levels should be accurately evaluated in the long-term follow-up, with individualized consideration for prophylactic nutritional, anti-inflammatory and/or anticoagulant therapy if indicated.}, } @article {pmid34366078, year = {2021}, author = {Tourette-Turgis, C and Salmon, D and Oustric, P and Hélie, F and Damamme, MR}, title = {[Patient experience, epistemic authority and health challenges: the example of long COVID].}, journal = {Soins; la revue de reference infirmiere}, volume = {66}, number = {857}, pages = {48-51}, doi = {10.1016/S0038-0814(21)00217-6}, pmid = {34366078}, issn = {0038-0814}, mesh = {*COVID-19/complications ; Humans ; Knowledge ; Patient Outcome Assessment ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since February 2020, hundreds of thousands of patients have been left with persistant symptoms after their infection. Along with their clinicians, these patients are exposed to a high degree of uncertainty and the urgent need to produce conceptual frameworks aimed at recognising, treating and validating their experience as patients suffering from new and protracted symptoms and witnessing debates as to how these symptoms should be qualified. In this respect, long covid illustrates the need to combine the collective experiential knowledge of patients and scientific knowledge for the benefit of the patients, clinicians and research.}, } @article {pmid34362372, year = {2021}, author = {Lam, GY and Befus, AD and Damant, RW and Ferrara, G and Fuhr, DP and Stickland, MK and Varughese, RA and Wong, EY and Smith, MP}, title = {Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?.}, journal = {Respiratory research}, volume = {22}, number = {1}, pages = {222}, pmid = {34362372}, issn = {1465-993X}, mesh = {Adult ; Aged ; COVID-19/*complications/epidemiology/physiopathology ; Dyspnea/epidemiology/*physiopathology ; Exercise Tolerance/*physiology ; Female ; Humans ; Lung/*physiology ; Male ; Middle Aged ; Oxygen Consumption/physiology ; *Phenotype ; Physical Exertion/*physiology ; Walk Test/methods ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed "long COVID". However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.}, } @article {pmid34361021, year = {2021}, author = {Cooper, SL and Boyle, E and Jefferson, SR and Heslop, CRA and Mohan, P and Mohanraj, GGJ and Sidow, HA and Tan, RCP and Hill, SJ and Woolard, J}, title = {Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.}, journal = {International journal of molecular sciences}, volume = {22}, number = {15}, pages = {}, pmid = {34361021}, issn = {1422-0067}, support = {MR/N020081/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Bradykinin/metabolism ; COVID-19/*complications ; Cardiovascular Diseases/drug therapy/*etiology ; Cytokine Release Syndrome/etiology/metabolism ; Humans ; *Kallikrein-Kinin System ; *Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin-Angiotensin-Aldosterone System (RAAS) and Kinin-Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.}, } @article {pmid34358460, year = {2021}, author = {Peluso, MJ and Deitchman, AN and Torres, L and Iyer, NS and Munter, SE and Nixon, CC and Donatelli, J and Thanh, C and Takahashi, S and Hakim, J and Turcios, K and Janson, O and Hoh, R and Tai, V and Hernandez, Y and Fehrman, EA and Spinelli, MA and Gandhi, M and Trinh, L and Wrin, T and Petropoulos, CJ and Aweeka, FT and Rodriguez-Barraquer, I and Kelly, JD and Martin, JN and Deeks, SG and Greenhouse, B and Rutishauser, RL and Henrich, TJ}, title = {Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms.}, journal = {Cell reports}, volume = {36}, number = {6}, pages = {109518}, pmid = {34358460}, issn = {2211-1247}, support = {R01 AI158013/AI/NIAID NIH HHS/United States ; K24 AI144048/AI/NIAID NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; R21 AI167648/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R01 HD068174/HD/NICHD NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; L30 AI126521/AI/NIAID NIH HHS/United States ; K23 AI146268/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/*complications/*immunology/pathology ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/*immunology ; Severity of Illness Index ; Virus Shedding/immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4[+] T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8[+] T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8[+] T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8[+] T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4[+] T cell responses.}, } @article {pmid34355349, year = {2021}, author = {Horwitz, LI and Garry, K and Prete, AM and Sharma, S and Mendoza, F and Kahan, T and Karpel, H and Duan, E and Hochman, KA and Weerahandi, H}, title = {Six-Month Outcomes in Patients Hospitalized with Severe COVID-19.}, journal = {Journal of general internal medicine}, volume = {36}, number = {12}, pages = {3772-3777}, pmid = {34355349}, issn = {1525-1497}, support = {K23 HL145110/HL/NHLBI NIH HHS/United States ; }, mesh = {Aftercare ; *COVID-19 ; Female ; Hospitalization ; Humans ; Patient Discharge ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Previous work has demonstrated that patients experience functional decline at 1-3 months post-discharge after COVID-19 hospitalization.

OBJECTIVE: To determine whether symptoms persist further or improve over time, we followed patients discharged after hospitalization for severe COVID-19 to characterize their overall health status and their physical and mental health at 6 months post-hospital discharge.

DESIGN: Prospective observational cohort study.

PARTICIPANTS: Patients ≥ 18 years hospitalized for COVID-19 at a single health system, who required at minimum 6 l of supplemental oxygen during admission, had intact baseline functional status, and were discharged alive.

MAIN MEASURES: Overall health status, physical health, mental health, and dyspnea were assessed with validated surveys: the PROMIS® Global Health-10 and PROMIS® Dyspnea Characteristics instruments.

KEY RESULTS: Of 152 patients who completed the 1 month post-discharge survey, 126 (83%) completed the 6-month survey. Median age of 6-month respondents was 62; 40% were female. Ninety-three (74%) patients reported that their health had not returned to baseline at 6 months, and endorsed a mean of 7.1 symptoms. Participants' summary t-scores in both the physical health and mental health domains at 6 months (45.2, standard deviation [SD] 9.8; 47.4, SD 9.8, respectively) remained lower than their baseline (physical health 53.7, SD 9.4; mental health 54.2, SD 8.0; p<0.001). Overall, 79 (63%) patients reported shortness of breath within the prior week (median score 2 out of 10 (interquartile range [IQR] 0-5), vs 42 (33%) pre-COVID-19 infection (0, IQR 0-1)). A total of 11/124 (9%) patients without pre-COVID oxygen requirements still needed oxygen 6 months post-hospital discharge. One hundred and seven (85%) were still experiencing fatigue at 6 months post-discharge.

CONCLUSIONS: Even 6 months after hospital discharge, the majority of patients report that their health has not returned to normal. Support and treatments to return these patients back to their pre-COVID baseline are urgently needed.}, } @article {pmid34354847, year = {2021}, author = {Qureshi, NK and Bansal, SK}, title = {Autoimmune Thyroid Disease and Psoriasis Vulgaris after COVID-19 in a Male Teenager.}, journal = {Case reports in pediatrics}, volume = {2021}, number = {}, pages = {7584729}, pmid = {34354847}, issn = {2090-6803}, abstract = {COVID-19 is implicated in triggering autoimmune, dermatologic, and thyroid diseases. We present a first known case of development of Graves' disease and psoriasis vulgaris in a previously healthy male teenager without any family history, diagnosed after COVID-19 infection. Evaluation of "long COVID syndrome" should include thorough history and thyroid evaluation.}, } @article {pmid34352201, year = {2021}, author = {Tosato, M and Carfì, A and Martis, I and Pais, C and Ciciarello, F and Rota, E and Tritto, M and Salerno, A and Zazzara, MB and Martone, AM and Paglionico, A and Petricca, L and Brandi, V and Capalbo, G and Picca, A and Calvani, R and Marzetti, E and Landi, F and , }, title = {Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study.}, journal = {Journal of the American Medical Directors Association}, volume = {22}, number = {9}, pages = {1840-1844}, pmid = {34352201}, issn = {1538-9375}, mesh = {Aged ; *COVID-19 ; Cross-Sectional Studies ; Female ; Humans ; Infant, Newborn ; Prevalence ; Quarantine ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: Symptom persistence weeks after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance is a relatively common long-term complication of Coronavirus disease 2019 (COVID-19). Little is known about this phenomenon in older adults. The present study aimed at determining the prevalence of persistent symptoms among older COVID-19 survivors and identifying symptom patterns.

DESIGN: Cross-sectional study.

SETTING AND PARTICIPANTS: We analyzed data collected in people 65 years and older (n = 165) who were hospitalized for COVID-19 and then admitted to the Day Hospital Post-COVID 19 of the Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS (Rome, Italy) between April and December 2020. All patients tested negative for SARS-CoV-2 and met the World Health Organization criteria for quarantine discontinuation.

MEASURES: Patients were offered multidisciplinary individualized assessments. The persistence of symptoms was evaluated on admission using a standardized questionnaire.

RESULTS: The mean age was 73.1 ± 6.2 years (median 72, interquartile range 27), and 63 (38.4%) were women. The average time elapsed from hospital discharge was 76.8 ± 20.3 days (range 25-109 days). On admission, 137 (83%) patients reported at least 1 persistent symptom. Of these, more than one-third reported 1 or 2 symptoms and 46.3% had 3 or more symptoms. The rate of symptom persistence was not significantly different when patients were stratified according to median age. Compared with those with no persistent symptoms, patients with symptom persistence reported a greater number of symptoms during acute COVID-19 (5.3 ± 3.0 vs 3.3 ± 2.0; P < .001). The most common persistent symptoms were fatigue (53.1%), dyspnea (51.5%), joint pain (22.2%), and cough (16.7%). The likelihood of symptom persistence was higher in those who had experienced fatigue during acute COVID-19.

CONCLUSIONS AND IMPLICATIONS: Persistent symptoms are frequently experienced by older adults who have been hospitalized for COVID-19. Follow-up programs should be implemented to monitor and care for long-term COVID-19-related health issues.}, } @article {pmid34351016, year = {2021}, author = {Munblit, D and Bobkova, P and Spiridonova, E and Shikhaleva, A and Gamirova, A and Blyuss, O and Nekliudov, N and Bugaeva, P and Andreeva, M and DunnGalvin, A and Comberiati, P and Apfelbacher, C and Genuneit, J and Avdeev, S and Kapustina, V and Guekht, A and Fomin, V and Svistunov, AA and Timashev, P and Subbot, VS and Royuk, VV and Drake, TM and Hanson, SW and Merson, L and Carson, G and Horby, P and Sigfrid, L and Scott, JT and Semple, MG and Warner, JO and Vos, T and Olliaro, P and Glybochko, P and Butnaru, D and , }, title = {Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {51}, number = {9}, pages = {1107-1120}, pmid = {34351016}, issn = {1365-2222}, support = {MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; INT 2021/RSM C 19 01//UK Embassy in Moscow/ ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; 20-04-60063//Russian Foundation for Basic Research/ ; }, mesh = {Adolescent ; Adult ; *Aftercare ; Aged ; Aged, 80 and over ; COVID-19/*epidemiology ; *COVID-19 Testing ; Female ; Follow-Up Studies ; *Hospitalization ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Russia/epidemiology ; *SARS-CoV-2 ; *Surveys and Questionnaires ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors.

METHODS: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire.

RESULTS: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32).

CONCLUSIONS: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.}, } @article {pmid34347785, year = {2021}, author = {Bell, ML and Catalfamo, CJ and Farland, LV and Ernst, KC and Jacobs, ET and Klimentidis, YC and Jehn, M and Pogreba-Brown, K}, title = {Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT.}, journal = {PloS one}, volume = {16}, number = {8}, pages = {e0254347}, pmid = {34347785}, issn = {1932-6203}, support = {P30 ES006694/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arizona/epidemiology ; COVID-19/*complications/diagnosis/epidemiology/pathology/rehabilitation ; Child ; Cohort Studies ; Disease Progression ; Female ; Home Care Services/statistics & numerical data ; Humans ; Male ; Middle Aged ; Prevalence ; Prognosis ; SARS-CoV-2/physiology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30-250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1-20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.}, } @article {pmid34345629, year = {2021}, author = {Johnsen, S and Sattler, SM and Miskowiak, KW and Kunalan, K and Victor, A and Pedersen, L and Andreassen, HF and Jørgensen, BJ and Heebøll, H and Andersen, MB and Marner, L and Hædersdal, C and Hansen, H and Ditlev, SB and Porsbjerg, C and Lapperre, TS}, title = {Descriptive analysis of long COVID sequelae identified in a multidisciplinary clinic serving hospitalised and non-hospitalised patients.}, journal = {ERJ open research}, volume = {7}, number = {3}, pages = {}, pmid = {34345629}, issn = {2312-0541}, abstract = {BACKGROUND: There are emerging data of long-term effects of coronavirus disease 2019 (COVID-19) comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra-pulmonary post-COVID-19 complications in relation to acute COVID-19 severity.

METHODS: Patients attending a standard of care 3 months post-hospitalisation follow-up visit and those referred by their general practitioner because of persistent post-COVID-19 symptoms were included. Patients underwent symptomatic, quality of life, pulmonary (lung function and high-resolution computed tomography (HRCT)), cardiac (high-resolution ECG), physical (1-min sit and stand test (1-MSTST), handgrip strength, cardiopulmonary exercise testing (CPET)) and cognitive evaluations.

RESULTS: All 34 hospitalised and 22 out of 23 non-hospitalised patients had ≥1 complaint or abnormal finding at follow-up. Overall, 67% of patients were symptomatic (Medical Research Council (MRC) ≥2 or COPD assessment test (CAT) ≥10), with no difference between hospitalised versus non-hospitalised patients. Pulmonary function (forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (D LCO)) <80% of predicted) was impaired in 68% of patients. D LCO was significantly lower in those hospitalised compared to non-hospitalised (70.1±18.0 versus 80.2±11.2% predicted, p=0.02). Overall, 53% had an abnormal HRCT (predominantly ground-glass opacities) with higher composite computed tomography (CT) scores in hospitalised versus non-hospitalised patients (2.3 (0.1-4.8) and 0.0 (0.0-0.3), p<0.001). 1-MSTST was below the 25th percentile in almost half of patients, but no signs of cardiac dysfunction were found. Cognitive impairments were present in 59-66% of hospitalised and 31-44% of non-hospitalised patients (p=0.08).

CONCLUSION: Three months after COVID-19 infection, patients were still symptomatic and demonstrated objective respiratory, functional, radiological and cognitive abnormalities, which were more prominent in hospitalised patients. Our study underlines the importance of multidimensional management strategies in these patients.}, } @article {pmid34344032, year = {2021}, author = {August, D and Götz, V and Stete, K}, title = {[Not Available].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {15}, pages = {972-977}, doi = {10.1055/a-1447-9253}, pmid = {34344032}, issn = {1439-4413}, mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Humans ; Prevalence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Some patients complain of persisting symptoms after acute COVID-19. There is no universal definition yet for these post-acute sequelae, also termed Long COVID. Although their prevalence remains to be established, a delayed recovery seems to be more common than after other acute infectious diseases. Common complaints include fatigue with exercise intolerance, dyspnea on exertion, chest pain, and neuropsychiatric symptoms. Female sex, comorbidities, and severity of the acute disease have been identified as risk factors for persisting symptoms. It is, however, important to highlight that they are not limited to patients after severe COVID-19. Whilst their pathogenesis and prognosis is largely unknown, diagnostic evaluation should focus on exclusion of objective organ dysfunctions. Due to the variable presentation, management is interdisciplinary and may include physiotherapy, rehabilitation programmes, and psychological support. This article aims to summarize the current - limited - evidence on persisting symptoms after COVID-19.}, } @article {pmid34343043, year = {2021}, author = {Palmer, SJ}, title = {Long COVID and mental health.}, journal = {British journal of community nursing}, volume = {26}, number = {8}, pages = {406-409}, doi = {10.12968/bjcn.2021.26.8.406}, pmid = {34343043}, issn = {1462-4753}, mesh = {Anxiety ; *COVID-19/complications/psychology ; Humans ; *Mental Health ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34341767, year = {2021}, author = {Robles Hernandez, LA and Callahan, TJ and Banda, JM}, title = {A Biomedically oriented automatically annotated Twitter COVID-19 Dataset.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {34341767}, issn = {2331-8422}, support = {P30 AG059307/AG/NIA NIH HHS/United States ; }, abstract = {The use of social media data, like Twitter, for biomedical research has been gradually increasing over the years. With the COVID-19 pandemic, researchers have turned to more nontraditional sources of clinical data to characterize the disease in near real-time, study the societal implications of interventions, as well as the sequelae that recovered COVID-19 cases present (Long-COVID). However, manually curated social media datasets are difficult to come by due to the expensive costs of manual annotation and the efforts needed to identify the correct texts. When datasets are available, they are usually very small and their annotations do not generalize well over time or to larger sets of documents. As part of the 2021 Biomedical Linked Annotation Hackathon, we release our dataset of over 120 million automatically annotated tweets for biomedical research purposes. Incorporating best practices, we identify tweets with potentially high clinical relevance. We evaluated our work by comparing several SpaCy-based annotation frameworks against a manually annotated gold-standard dataset. Selecting the best method to use for automatic annotation, we then annotated 120 million tweets and released them publicly for future downstream usage within the biomedical domain.}, } @article {pmid34340970, year = {2021}, author = {Walker, AJ and MacKenna, B and Inglesby, P and Tomlinson, L and Rentsch, CT and Curtis, HJ and Morton, CE and Morley, J and Mehrkar, A and Bacon, S and Hickman, G and Bates, C and Croker, R and Evans, D and Ward, T and Cockburn, J and Davy, S and Bhaskaran, K and Schultze, A and Williamson, EJ and Hulme, WJ and McDonald, HI and Mathur, R and Eggo, RM and Wing, K and Wong, AY and Forbes, H and Tazare, J and Parry, J and Hester, F and Harper, S and O'Hanlon, S and Eavis, A and Jarvis, R and Avramov, D and Griffiths, P and Fowles, A and Parkes, N and Douglas, IJ and Evans, SJ and , }, title = {Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {712}, pages = {e806-e814}, pmid = {34340970}, issn = {1478-5242}, support = {MC_PC_20059/MRC_/Medical Research Council/United Kingdom ; MC_PC_20051/MRC_/Medical Research Council/United Kingdom ; MR/S003940/1/MRC_/Medical Research Council/United Kingdom ; MR/S003975/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20030/MRC_/Medical Research Council/United Kingdom ; MC_PC_20058/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; *Clinical Coding ; Cohort Studies ; England ; Female ; Humans ; Male ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID describes new or persistent symptoms at least 4 weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were recently created.

AIM: To describe the use of long-COVID codes, and variation of use by general practice, demographic variables, and over time.

DESIGN AND SETTING: Population-based cohort study in English primary care.

METHOD: Working on behalf of NHS England, OpenSAFELY data were used encompassing 96% of the English population between 1 February 2020 and 25 May 2021. The proportion of people with a recorded code for long COVID was measured overall and by demographic factors, electronic health record software system (EMIS or TPP), and week.

RESULTS: Long COVID was recorded for 23 273 people. Coding was unevenly distributed among practices, with 26.7% of practices having never used the codes. Regional variation ranged between 20.3 per 100 000 people for East of England (95% confidence interval [CI] = 19.3 to 21.4) and 55.6 per 100 000 people in London (95% CI = 54.1 to 57.1). Coding was higher among females (52.1, 95% CI = 51.3 to 52.9) than males (28.1, 95% CI = 27.5 to 28.7), and higher among practices using EMIS (53.7, 95% CI = 52.9 to 54.4) than those using TPP (20.9, 95% CI = 20.3 to 21.4).

CONCLUSION: Current recording of long COVID in primary care is very low, and variable between practices. This may reflect patients not presenting; clinicians and patients holding different diagnostic thresholds; or challenges with the design and communication of diagnostic codes. Increased awareness of diagnostic codes is recommended to facilitate research and planning of services, and also surveys with qualitative work to better evaluate clinicians' understanding of the diagnosis.}, } @article {pmid34340958, year = {2021}, author = {Rodríguez-Alfonso, B and Ruiz Solís, S and Silva-Hernández, L and Pintos Pascual, I and Aguado Ibáñez, S and Salas Antón, C}, title = {[18]F-FDG-PET/CT in SARS-CoV-2 infection and its sequelae.}, journal = {Revista espanola de medicina nuclear e imagen molecular}, volume = {40}, number = {5}, pages = {299-309}, pmid = {34340958}, issn = {2253-8089}, mesh = {COVID-19/*complications/*diagnostic imaging ; *Fluorodeoxyglucose F18 ; Humans ; *Positron Emission Tomography Computed Tomography/methods ; *Radiopharmaceuticals ; }, abstract = {In recent months, much of the scientific efforts have focused on research on SARSCoV-2 infection and its consequences in humans. Still, many aspects remain unknown. It is known that the damage caused by SARS-CoV-2 is multifactorial and that its extension goes beyond lung inflammation and the acute phase, with the appearance of numerous complications and sequelae. To date, knowledge about the usefulness of [18]F-FDG-PET/CT in the acute phase has been limited to the incidental detection of SARS-CoV-2 unsuspected pneumonia. Recent studies have been appearing collecting the findings of [18]F-FDG-PET/CT in long COVID-19 or persistent COVID-19 state as well as the alterations caused after mass vaccination of the population in the metabolic studies. This work aims to review the existing literature focusing on these three issues and to briefly present our own preliminary experience.}, } @article {pmid34339806, year = {2021}, author = {Schou, TM and Joca, S and Wegener, G and Bay-Richter, C}, title = {Psychiatric and neuropsychiatric sequelae of COVID-19 - A systematic review.}, journal = {Brain, behavior, and immunity}, volume = {97}, number = {}, pages = {328-348}, pmid = {34339806}, issn = {1090-2139}, mesh = {Anxiety ; Anxiety Disorders ; *COVID-19 ; Female ; Humans ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; }, abstract = {It has become evident that coronavirus disease 2019 (COVID-19) has a multi-organ pathology that includes the brain and nervous system. Several studies have also reported acute psychiatric symptoms in COVID-19 patients. An increasing number of studies are suggesting that psychiatric deficits may persist after recovery from the primary infection. In the current systematic review, we provide an overview of the available evidence and supply information on potential risk factors and underlying biological mechanisms behind such psychiatric sequelae. We performed a systematic search for psychiatric sequelae in COVID-19 patients using the databases PubMed and Embase. Included primary studies all contained information on the follow-up period and provided quantitative measures of mental health. The search was performed on June 4th 2021. 1725 unique studies were identified. Of these, 66 met the inclusion criteria and were included. Time to follow-up ranged from immediately after hospital discharge up to 7 months after discharge, and the number of participants spanned 3 to 266,586 participants. Forty studies reported anxiety and/or depression, 20 studies reported symptoms- or diagnoses of post-traumatic stress disorder (PTSD), 27 studies reported cognitive deficits, 32 articles found fatigue at follow-up, and sleep disturbances were found in 23 studies. Highlighted risk factors were disease severity, duration of symptoms, and female sex. One study showed brain abnormalities correlating with cognitive deficits, and several studies reported inflammatory markers to correlate with symptoms. Overall, the results from this review suggest that survivors of COVID-19 are at risk of psychiatric sequelae but that symptoms generally improve over time.}, } @article {pmid34336872, year = {2021}, author = {Ali, I and Ali, S and Iqbal, S}, title = {COVID-19 Vaccination: Concerns About Its Accessibility, Affordability, and Acceptability.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {647294}, pmid = {34336872}, issn = {2296-858X}, abstract = {By the mid of June 2021, after an almost 1.5-year-long COVID-19 pandemic that has significantly affected the world in multiple ways, various vaccines against COVID-19 have arrived and started worldwide. Yet, economic, (geo)political, and socio-cultural factors may influence its uptake at individual and country levels. Several issues will (and already have been reported in media) revolve around this vaccination regarding its accessibility, affordability, and acceptability at an individual level and a country level. Given that in this commentary, we provoke a discussion: Who-a country as well as the individuals-would have access to it, and who would economically afford it, and who would accept it? Centering these intriguing questions, we revisit the body of literature that explicates vaccine hesitancy, refusal, and resistance, and we also draw on the current literature and media reports about vaccination against COVID-19. We suggest that these backdrops need essential attention so that everyone can afford, accept, and have access to it. Otherwise, the current risk in the face of a year-old pandemic will continue.}, } @article {pmid34336725, year = {2021}, author = {Srinivasan, M}, title = {Taste Dysfunction and Long COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {716563}, pmid = {34336725}, issn = {2235-2988}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Taste Disorders ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34333907, year = {2021}, author = {Halaçlı, B and Topeli, A}, title = {Implementation of post-intensive care outpatient clinic (I-POINT) for critically ill COVID-19 survivors.}, journal = {Turkish journal of medical sciences}, volume = {51}, number = {SI-1}, pages = {3350-3358}, pmid = {34333907}, issn = {1303-6165}, mesh = {Ambulatory Care Facilities ; COVID-19/*complications/diagnosis/therapy ; Critical Care/*methods ; Critical Illness ; Humans ; Intensive Care Units ; Pandemics ; Respiratory Distress Syndrome/*therapy ; SARS-CoV-2 ; Survivors ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although we have enough and cumulative information about acute effects of COVID-19, our knowledge is extremely limited about long-term consequences of COVID-19, in terms of its impacts and burdens on patients, families, and the health system. Considering the underlying pathophysiological mechanisms affecting all of the organ systems in critically ill COVID-19 patients who are admitted to intensive care units, the development of post-intensive care syndrome is inevitable. This situation brings along the development of long-COVID. These patients should be followed regarding cognitive, physical, and psychiatric aspects and necessary specialist referrals should be carried out. In this article, we are presenting the experience and recommendations of our center, as a guide for the establishment process of post-intensive care outpatient clinics for the critically ill patients who required intensive care admission due to COVID-19 and could be discharged.}, } @article {pmid34328636, year = {2021}, author = {Piotrowicz, K and Gąsowski, J and Michel, JP and Veronese, N}, title = {Post-COVID-19 acute sarcopenia: physiopathology and management.}, journal = {Aging clinical and experimental research}, volume = {33}, number = {10}, pages = {2887-2898}, pmid = {34328636}, issn = {1720-8319}, mesh = {Aged ; *COVID-19/complications ; Communicable Disease Control ; Humans ; SARS-CoV-2 ; *Sarcopenia/therapy ; Post-Acute COVID-19 Syndrome ; }, abstract = {In this review, we discuss the pathophysiologic and management aspects of acute sarcopenia in relation to SARS-CoV-2 infection. COVID-19 is as a multi-organ infectious disease characterized by a severe inflammatory and highly catabolic status, influencing the deep changes in the body build, especially the amount, structure, and function of skeletal muscles which would amount to acutely developed sarcopenia. Acute sarcopenia may largely impact patients' in-hospital prognosis as well as the vulnerability to the post-COVID-19 functional and physical deterioration. The individual outcome of the COVID-19 and the degree of muscle mass and functional loss may be influenced by multiple factors, including the patient's general pre-infection medical and functional condition, especially in older adults. This paper gathers the information about how the SARS-CoV-2 hyper-inflammatory involvement exacerbates the immunosenescence process, enhances the endothelial damage, and due to mitochondrial dysfunction and autophagy, induces myofibrillar breakdown and muscle degradation. The aftermath of these acute and complex immunological SARS-CoV-2-related phenomena, augmented by anosmia, ageusia and altered microbiota may lead to decreased food intake and exacerbated catabolism. Moreover, the imposed physical inactivity, lock-down, quarantine or acute hospitalization with bedrest would intensify the acute sarcopenia process. All these deleterious mechanisms must be swiftly put to a check by a multidisciplinary approach including nutritional support, early physical as well cardio-pulmonary rehabilitation, and psychological support and cognitive training. The proposed holistic and early management of COVID-19 patients appears essential to minimize the disastrous functional outcomes of this disease and allow avoiding the long COVID-19 syndrome.}, } @article {pmid34326224, year = {2021}, author = {Alwan, NA}, title = {The road to addressing Long Covid.}, journal = {Science (New York, N.Y.)}, volume = {373}, number = {6554}, pages = {491-493}, doi = {10.1126/science.abg7113}, pmid = {34326224}, issn = {1095-9203}, mesh = {Activities of Daily Living ; Biomedical Research ; COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Epidemiological Monitoring ; Female ; Humans ; Male ; Mental Health ; Prevalence ; Self-Help Groups ; Social Media ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34321226, year = {2021}, author = {Malcolm, RS}, title = {Chronic fatigue syndrome and long covid: individualisation, not compartmentalisation.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1863}, doi = {10.1136/bmj.n1863}, pmid = {34321226}, issn = {1756-1833}, mesh = {*COVID-19/complications ; *Fatigue Syndrome, Chronic ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34321219, year = {2021}, author = {Davidson, SL and Menkes, DB}, title = {Long covid: reshaping conversations about medically unexplained symptoms.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1859}, doi = {10.1136/bmj.n1859}, pmid = {34321219}, issn = {1756-1833}, mesh = {*COVID-19/complications ; Humans ; *Medically Unexplained Symptoms ; SARS-CoV-2 ; Somatoform Disorders ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34319569, year = {2021}, author = {Akbarialiabad, H and Taghrir, MH and Abdollahi, A and Ghahramani, N and Kumar, M and Paydar, S and Razani, B and Mwangi, J and Asadi-Pooya, AA and Malekmakan, L and Bastani, B}, title = {Long COVID, a comprehensive systematic scoping review.}, journal = {Infection}, volume = {49}, number = {6}, pages = {1163-1186}, pmid = {34319569}, issn = {1439-0973}, support = {K43 TW010716/TW/FIC NIH HHS/United States ; }, mesh = {*COVID-19/complications ; Fatigue ; Humans ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021.

METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist.

RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management).

CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.}, } @article {pmid34316551, year = {2021}, author = {Hampshire, A and Trender, W and Chamberlain, SR and Jolly, AE and Grant, JE and Patrick, F and Mazibuko, N and Williams, SC and Barnby, JM and Hellyer, P and Mehta, MA}, title = {Cognitive deficits in people who have recovered from COVID-19.}, journal = {EClinicalMedicine}, volume = {39}, number = {}, pages = {101044}, pmid = {34316551}, issn = {2589-5370}, abstract = {BACKGROUND: There is growing concern about possible cognitive consequences of COVID-19, with reports of 'Long COVID' symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.

METHODS: We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.

FINDINGS: People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.

INTERPRETATION: Interpretation. These results accord with reports of 'Long Covid' cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.

FUNDING: Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.}, } @article {pmid34316076, year = {2021}, author = {Visan, I}, title = {Long COVID.}, journal = {Nature immunology}, volume = {22}, number = {8}, pages = {934-935}, doi = {10.1038/s41590-021-00992-4}, pmid = {34316076}, issn = {1529-2916}, } @article {pmid34312178, year = {2021}, author = {Crook, H and Raza, S and Nowell, J and Young, M and Edison, P}, title = {Long covid-mechanisms, risk factors, and management.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1648}, doi = {10.1136/bmj.n1648}, pmid = {34312178}, issn = {1756-1833}, mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Clinical Trials as Topic ; Combined Modality Therapy/methods/standards ; Drug Repositioning ; Global Burden of Disease ; Humans ; Incidence ; Practice Guidelines as Topic ; Risk Factors ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.}, } @article {pmid34312122, year = {2022}, author = {Bitirgen, G and Korkmaz, C and Zamani, A and Ozkagnici, A and Zengin, N and Ponirakis, G and Malik, RA}, title = {Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID.}, journal = {The British journal of ophthalmology}, volume = {106}, number = {12}, pages = {1635-1641}, pmid = {34312122}, issn = {1468-2079}, mesh = {Humans ; *COVID-19 ; Cross-Sectional Studies ; SARS-CoV-2 ; Microscopy, Confocal ; Cornea/innervation ; Nerve Fibers ; Dendritic Cells ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND/AIMS: Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.

METHODS: Forty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.

RESULTS: The mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=-0.436; p=0.005, ρ=-0.387; p=0.038, respectively) and CNFL (ρ=-0.404; p=0.010, ρ=-0.412; p=0.026, respectively).

CONCLUSION: Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.}, } @article {pmid34308300, year = {2021}, author = {Davis, HE and Assaf, GS and McCorkell, L and Wei, H and Low, RJ and Re'em, Y and Redfield, S and Austin, JP and Akrami, A}, title = {Characterizing long COVID in an international cohort: 7 months of symptoms and their impact.}, journal = {EClinicalMedicine}, volume = {38}, number = {}, pages = {101019}, pmid = {34308300}, issn = {2589-5370}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. Few systematic studies have investigated this population, particularly in outpatient settings. Hence, relatively little is known about symptom makeup and severity, expected clinical course, impact on daily functioning, and return to baseline health.

METHODS: We conducted an online survey of people with suspected and confirmed COVID-19, distributed via COVID-19 support groups (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters) and social media (e.g. Twitter, Facebook). Data were collected from September 6, 2020 to November 25, 2020. We analyzed responses from 3762 participants with confirmed (diagnostic/antibody positive; 1020) or suspected (diagnostic/antibody negative or untested; 2742) COVID-19, from 56 countries, with illness lasting over 28 days and onset prior to June 2020. We estimated the prevalence of 203 symptoms in 10 organ systems and traced 66 symptoms over seven months. We measured the impact on life, work, and return to baseline health.

FINDINGS: For the majority of respondents (>91%), the time to recovery exceeded 35 weeks. During their illness, participants experienced an average of 55.9+/- 25.5 (mean+/-STD) symptoms, across an average of 9.1 organ systems. The most frequent symptoms after month 6 were fatigue, post-exertional malaise, and cognitive dysfunction. Symptoms varied in their prevalence over time, and we identified three symptom clusters, each with a characteristic temporal profile. 85.9% of participants (95% CI, 84.8% to 87.0%) experienced relapses, primarily triggered by exercise, physical or mental activity, and stress. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 1700 respondents (45.2%) required a reduced work schedule compared to pre-illness, and an additional 839 (22.3%) were not working at the time of survey due to illness. Cognitive dysfunction or memory issues were common across all age groups (~88%). Except for loss of smell and taste, the prevalence and trajectory of all symptoms were similar between groups with confirmed and suspected COVID-19.

INTERPRETATION: Patients with Long COVID report prolonged, multisystem involvement and significant disability. By seven months, many patients have not yet recovered (mainly from systemic and neurological/cognitive symptoms), have not returned to previous levels of work, and continue to experience significant symptom burden.

FUNDING: All authors contributed to this work in a voluntary capacity. The cost of survey hosting (on Qualtrics) and publication fee was covered by AA's research grant (Wellcome Trust/Gatsby Charity via Sainsbury Wellcome center, UCL).}, } @article {pmid34302866, year = {2021}, author = {Ladhani, SN}, title = {Crossing the Rubicon: A fine line between waiting and vaccinating adolescents against COVID-19.}, journal = {The Journal of infection}, volume = {83}, number = {3}, pages = {294-297}, pmid = {34302866}, issn = {1532-2742}, mesh = {Adolescent ; *COVID-19/complications ; *COVID-19 Vaccines ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Several countries with advanced adult COVID-19 immunisation programmes have already started vaccinating adolescents with an mRNA vaccine that recently received emergency use authorisation for 12-15 year-olds. The decision to vaccinate adolescents remains highly divisive among parents, clinicians, politicians and policy makers. There are very few downsides to immunising adolescents with a safe and effective COVID-19 vaccine because that would significantly reduce their risk of COVID-19 and all its complications. Based on current evidence, however, adolescents have a very low risk of severe or fatal COVID-19, even among those with comorbidities, or rare complications such as long COVID or Paediatric Multisystem Inflammatory Syndrome (PIMS-TS), a hyperinflammatory syndrome temporally associated with SARS-CoV-2. Additionally, currently authorised vaccines are very reactogenic and have limited post-marketing population-level safety data in adolescents and young adults, but these are emerging from countries that have forged ahead with vaccinating adolescents. Countries that have yet to make a recommendation can afford to wait until there is sufficient information to make informed decisions on the risk-benefits of vaccinating adolescents with current and future COVID-19 vaccines. Alternatives to two-dose vaccination in adolescents may include a single dose or a reduced dose schedule as is currently being trialled in younger children.}, } @article {pmid34290398, year = {2021}, author = {Pérez-Gómez, A and Vitallé, J and Gasca-Capote, C and Gutierrez-Valencia, A and Trujillo-Rodriguez, M and Serna-Gallego, A and Muñoz-Muela, E and Jiménez-Leon, MLR and Rafii-El-Idrissi Benhnia, M and Rivas-Jeremias, I and Sotomayor, C and Roca-Oporto, C and Espinosa, N and Infante-Domínguez, C and Crespo-Rivas, JC and Fernández-Villar, A and Pérez-González, A and López-Cortés, LF and Poveda, E and Ruiz-Mateos, E and , }, title = {Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection.}, journal = {Cellular & molecular immunology}, volume = {18}, number = {9}, pages = {2128-2139}, pmid = {34290398}, issn = {2042-0226}, support = {CM20/00243//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; FI19/00083//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CP19/00159//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; }, mesh = {COVID-19/*immunology ; Cells, Cultured ; Dendritic Cells/*immunology ; Female ; Humans ; Immunity, Innate/immunology ; Inflammation/immunology ; Interferon-alpha/immunology ; Leukocytes, Mononuclear/immunology ; Male ; SARS-CoV-2/*immunology ; Severity of Illness Index ; }, abstract = {Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.}, } @article {pmid34288064, year = {2021}, author = {Roe, K}, title = {A role for T-cell exhaustion in Long COVID-19 and severe outcomes for several categories of COVID-19 patients.}, journal = {Journal of neuroscience research}, volume = {99}, number = {10}, pages = {2367-2376}, pmid = {34288064}, issn = {1097-4547}, mesh = {COVID-19/*complications/*immunology/mortality/therapy ; Humans ; T-Lymphocytes/*immunology ; Toxoplasmosis/*complications/mortality ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Unusual mortality rate differences and symptoms have been experienced by COVID-19 patients, and the postinfection symptoms called Long COVID-19 have also been widely experienced. A substantial percentage of COVID-19-infected individuals in specific health categories have been virtually asymptomatic, several other individuals in the same health categories have exhibited several unusual symptoms, and yet other individuals in the same health categories have fatal outcomes. It is now hypothesized that these differences in mortality rates and symptoms could be caused by a SARS-CoV-2 virus infection acting together with one or more latent pathogen infections in certain patients, through mutually beneficial induced immune cell dysfunctions, including T-cell exhaustion. A latent pathogen infection likely to be involved is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. Furthermore, certain infections and cancers that cause T-cell exhaustion can also explain the more severe outcomes of other COVID-19 patients having several disease and cancer comorbidities.}, } @article {pmid34286502, year = {2021}, author = {Lagadinou, M and Kostopoulou, E and Karatza, A and Marangos, M and Gkentzi, D}, title = {The prolonged effects of COVID-19. A new "threat"?.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {13}, pages = {4611-4615}, doi = {10.26355/eurrev_202107_26253}, pmid = {34286502}, issn = {2284-0729}, mesh = {COVID-19/*diagnosis/epidemiology ; Humans ; Pandemics ; Quality of Life ; Risk Factors ; SARS-CoV-2/isolation & purification ; }, abstract = {Coronavirus 'long-haulers" currently represent a significant public health concern. Recent reports suggest that persistent effects of COVID-19, such as fatigue, dyspnea, chest pain, anxiety, depression, arthralgia, may last for months and lead to a decline in quality of life. Risk factors for long COVID are still not very well understood. Survivors suffer from ongoing symptoms. This new entity highlights the need for a multidisciplinary approach that would enable closer monitoring of affected patients and implementation of measures that could reduce the impact of the pandemic on the overall patient wellbeing after the resolution of acute symptoms.}, } @article {pmid34284531, year = {2021}, author = {Petersen, E and Gökengin, D and Al Balushi, A and Zumla, A}, title = {One and a half years into the COVID-19 pandemic - exit strategies and efficacy of SARS-CoV-2 vaccines for holistic management and achieving global control.}, journal = {Turkish journal of medical sciences}, volume = {51}, number = {SI-1}, pages = {3157-3161}, pmid = {34284531}, issn = {1303-6165}, mesh = {Aged ; COVID-19/complications/epidemiology/genetics/*prevention & control/transmission ; COVID-19 Vaccines/immunology ; Child ; Communicable Disease Control ; Humans ; Pandemics/*prevention & control ; Population Surveillance/*methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {One and a half years into the pandemic, SARS-CoV-2 is still here to stay. Whilst rapid several effective COVID-19 vaccines have been developed and are being rolled out, the critical questions remain whether vaccines provide widespread protection against infection and reinfection, and what the duration of protection is. Community wide control cannot be obtained until almost everyone is immune. Vaccine production must be ramped up to cover the world population. The price of herd immunity through natural infection is high mortality in the elderly and morbidity in other age groups including children and Long-COVID. We must expect a new wave in the coming winter. The severity will depend on the proportion of the population with immunity from natural infections or immunisation. Therefore, control rests on a population wide immunisation including children, which may or may not need to be repeated if new SARS-CoV-2 variants evolve that can escape immunity from either previous infections or immunisations. Preventing long term sequelae of COVID-19 also remains a priority.}, } @article {pmid34283545, year = {2021}, author = {Ivanova, GE and Bogolepova, AN and Levin, OS and Shamalov, NA and Khasanova, DR and Yanishevsky, SN and Zakharov, VV and Khatkova, SE and Stakhovskya, LV}, title = {[Current issues of treatment and rehabilitation of patients with neurological disorders and the consequences of COVID-19. Resolution of Advisory Board].}, journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova}, volume = {121}, number = {6}, pages = {145-151}, doi = {10.17116/jnevro2021121061145}, pmid = {34283545}, issn = {1997-7298}, mesh = {Brain ; *COVID-19 ; Humans ; *Nervous System Diseases/epidemiology ; Pandemics ; SARS-CoV-2 ; }, abstract = {Last year the global medical community faced the pandemic of the new coronavirus infection caused by SARS-CoV-2. To date, there is considerable expert experience, which indicates that the brain, along with the corresponding respiratory system, is a target organ for a new coronavirus infection. Moreover, a number of symptoms from the central and peripheral nervous system can persist for several weeks, months, and even tens of months. To designate such protracted clinical conditions, a new definition was introduced: «Post-COVID-19 Condition». Advisory Board of Neurologists and Rehabilitation Therapists met to, discuss of practical experience and taking into account scientific information about COVID-19, which was available at the time of the meeting, to develop unified approaches for the management of patients with neurological complications and the consequences of a new coronavirus infection. The Advisory Board worked out a resolution in which formulated the tactics of managing patients with neurological manifestations of COVID-19. The substantiation of the importance and expediency of the development and implementation of a special program of clinical examination of patients who have undergone COVID-19, which would include a clinical examination with a detailed assessment of cognitive functions to early identification and diagnosis of neurodegeneration and subsequent therapy, is given.}, } @article {pmid34281723, year = {2022}, author = {Thompson, CM and Rhidenour, KB and Blackburn, KG and Barrett, AK and Babu, S}, title = {Using crowdsourced medicine to manage uncertainty on Reddit: The case of COVID-19 long-haulers.}, journal = {Patient education and counseling}, volume = {105}, number = {2}, pages = {322-330}, pmid = {34281723}, issn = {1873-5134}, mesh = {*COVID-19/complications ; *Crowdsourcing ; Humans ; SARS-CoV-2 ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Causes of and treatments for long-COVID syndrome remain unknown. Drawing on uncertainty management theory (UMT), this study elucidates the communicative nature of crowdsourced medicine as a means by which COVID "long-haulers" respond to their poorly understood illness.

METHODS: 31,892 posts on the long-haulers subreddit (r/covidlonghaulers) were analyzed, starting with its creation date, July 24th, 2020, until January 7, 2021. The Meaning Extraction Method was used to identify clusters of words that mathematically group together across the text observations.

RESULTS: Analyses yielded 16 distinct factors of words, which we thematized based on their composition, the data, and UMT. The 16 themes encompassed symptoms (e.g., pain, respiratory, sensory), diagnostic concerns (testing, diagnosis), broad health concerns (immunity, physical activity, diet), chronicity, support, identity, and anxiety.

CONCLUSION: Findings provide a succinct, yet robust set of themes reflecting the information-seeking (i.e., "This is happening to me") and support-seeking functions of long-haulers' talk (i.e., "Is this happening to you?"). Findings have implications for collective uncertainty management, online crowdsourcing, and patient advocacy.

PRACTICE IMPLICATIONS: We recommend that health care providers employ sensitivity when addressing the anxiety that long-haulers are experiencing while also validating that their physical symptoms are real. Online communities help long-haulers manage their uncertainty.}, } @article {pmid34276671, year = {2021}, author = {Ramakrishnan, RK and Kashour, T and Hamid, Q and Halwani, R and Tleyjeh, IM}, title = {Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {686029}, pmid = {34276671}, issn = {1664-3224}, mesh = {Anxiety/etiology ; Arthralgia/etiology ; Autoimmunity ; COVID-19/*complications/epidemiology/immunology/virology ; Depression/etiology ; Dyspnea/etiology ; Fatigue/etiology ; Gastrointestinal Microbiome/immunology ; Humans ; Immunocompromised Host ; Incidence ; Prevalence ; Renin-Angiotensin System/immunology ; SARS-CoV-2/*immunology ; Post-Acute COVID-19 Syndrome ; }, abstract = {More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.}, } @article {pmid34275164, year = {2022}, author = {Johnson, AS and Winlow, W}, title = {COVID-19 vulnerabilities are intensified by declining human serum albumin levels.}, journal = {Experimental physiology}, volume = {107}, number = {7}, pages = {674-682}, pmid = {34275164}, issn = {1469-445X}, mesh = {*COVID-19/complications ; Humans ; Ligands ; Protein Binding ; SARS-CoV-2 ; Serum Albumin/metabolism/therapeutic use ; Serum Albumin, Human/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {What is the topic of this review? Human serum albumin (HSA) a common factor in COVID-19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID-19. Raising HSA in COVID-19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. ABSTRACT: The specific nature of the vulnerabilities to COVID-19 are an intrinsic part of COVID-19 infection in many patients. This paper proposes that vulnerabilities to COVID-19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID-19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID-19 and long-COVID-19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID-19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID-19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS-CoV-2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.}, } @article {pmid34273510, year = {2021}, author = {Darcis, G and Bouquegneau, A and Maes, N and Thys, M and Henket, M and Labye, F and Rousseau, AF and Canivet, P and Desir, C and Calmes, D and Schils, R and De Worm, S and Léonard, P and Meunier, P and Moutschen, M and Louis, R and Guiot, J}, title = {Long-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: a monocentric prospective observational cohort study.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {109}, number = {}, pages = {209-216}, pmid = {34273510}, issn = {1878-3511}, mesh = {*COVID-19 ; Cohort Studies ; Follow-Up Studies ; Humans ; Prospective Studies ; SARS-CoV-2 ; }, abstract = {OBJECTIVES: Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Uncertainty remains about the potential mid- and long-term health sequelae. This prospective study of patients hospitalized with coronavirus disease 2019 (COVID-19) in Liège University Hospital, Belgium aimed to determine the persistent consequences of COVID-19.

METHODS: Patients admitted to the University Hospital of Liège with moderate-to-severe confirmed COVID-19, discharged between 2 March and 1 October 2020, were recruited prospectively. Follow-up at 3 and 6 months after hospital discharge included demographic and clinical data, biological data, pulmonary function tests (PFTs) and high-resolution computed tomography (CT) scans of the chest.

RESULTS: In total, 199 individuals were included in the analysis. Most patients received oxygen supplementation (80.4%). Six months after discharge, 47% and 32% of patients still had exertional dyspnoea and fatigue. PFTs at 3-month follow-up revealed a reduced diffusion capacity of carbon monoxide (mean 71.6 ± 18.6%), and this increased significantly at 6-month follow-up (P<0.0001). Chest CT scans showed a high prevalence (68.9% of the cohort) of persistent abnormalities, mainly ground glass opacities. Duration of hospitalization, intensive care unit admission and mechanical ventilation were not associated with the persistence of symptoms 3 months after discharge.

CONCLUSION: The prevalence of persistent symptoms following hospitalization with COVID-19 is high and stable for up to 6 months after discharge. However, biological, functional and iconographic abnormalities improved significantly over time.}, } @article {pmid34273064, year = {2021}, author = {García-Abellán, J and Padilla, S and Fernández-González, M and García, JA and Agulló, V and Andreo, M and Ruiz, S and Galiana, A and Gutiérrez, F and Masiá, M}, title = {Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study.}, journal = {Journal of clinical immunology}, volume = {41}, number = {7}, pages = {1490-1501}, pmid = {34273064}, issn = {1573-2592}, support = {RD16/0025/0038//Instituto de Salud Carlos III/ ; PI16/01740//Instituto de Salud Carlos III/ ; PI18/01861//Instituto de Salud Carlos III/ ; CM19/00160//Instituto de Salud Carlos III/ ; CM20/00066//Instituto de Salud Carlos III/ ; COV20/00005//Instituto de Salud Carlos III/ ; COV20/00156//Instituto de Salud Carlos III/ ; }, mesh = {Adult ; Aged ; Antibodies, Viral/blood ; Antibody Formation ; COVID-19/*complications/diagnosis/*immunology/mortality ; Female ; Hospitalization ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; SARS-CoV-2/*physiology ; Severity of Illness Index ; Sex Factors ; Survival Analysis ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The relationship of host immune response and viral replication with health outcomes in patients with COVID-19 remains to be defined. We aimed to characterize the medium and long-term clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.

METHODS: Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.

RESULTS: Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct = 38) and 3% (median Ct = 36) patients at 2 months and 6 months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO severity score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral RNA shedding.

CONCLUSIONS: Long-COVID is associated with weak anti-SARS-CoV-2 antibody response, severity of illness, and female gender. Late clinical events and persistent symptoms in the medium and long term occur in a significant proportion of patients hospitalized for COVID-19.}, } @article {pmid34270990, year = {2021}, author = {List, JM and Long, TG}, title = {Community-Based Primary Care Management of 'Long COVID': A Center of Excellence Model at NYC Health+ Hospitals.}, journal = {The American journal of medicine}, volume = {134}, number = {10}, pages = {1232-1235}, pmid = {34270990}, issn = {1555-7162}, mesh = {COVID-19/*complications/therapy ; Female ; Hospitals ; Humans ; Male ; New York City ; *Patient-Centered Care ; *Primary Health Care ; SARS-CoV-2 ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34268556, year = {2022}, author = {van Kessel, SAM and Olde Hartman, TC and Lucassen, PLBJ and van Jaarsveld, CHM}, title = {Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review.}, journal = {Family practice}, volume = {39}, number = {1}, pages = {159-167}, pmid = {34268556}, issn = {1460-2229}, mesh = {*COVID-19/complications ; Cough/etiology ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild (managed in the outpatient setting) COVID-19 infection. Currently, research on these persistent symptoms mainly focuses on patients with severe infections (managed in an inpatient setting) whereas patients with mild disease are rarely studied.

OBJECTIVE: The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID-19 infection.

METHODS: Systematic literature searches were performed in Pubmed, Embase and PsychINFO on 2 February 2021. Quantitative studies, qualitative studies, clinical lessons and case reports were considered eligible designs.

RESULTS: In total, nine articles were included in this literature review. The frequency of persistent symptoms in patients after mild COVID-19 infection ranged between 10% and 35%. Symptoms persisting after a mild COVID-19 infection can be distinguished into physical, mental and social symptoms. Fatigue was the most frequently described persistent symptom. Other frequently occurring persistent symptoms were dyspnoea, cough, chest pain, headache, decreased mental and cognitive status and olfactory dysfunction. In addition, it was found that persisting symptoms after a mild COVID-19 infection can have major consequences for work and daily functioning.

CONCLUSION: There is already some evidence that symptoms of mild COVID-19 persist after 3 weeks in a third of patients. However, there is a lack of data about symptoms persisting after 3 months (long-COVID). More research is needed to help GPs in managing long-COVID.}, } @article {pmid34268454, year = {2021}, author = {Yuen, KCJ and Mortensen, MJ and Azadi, A and Fonkem, E and Findling, JW}, title = {Rethinking the management of immune checkpoint inhibitor-related adrenal insufficiency in cancer patients during the COVID-19 pandemic.}, journal = {Endocrinology, diabetes & metabolism}, volume = {4}, number = {3}, pages = {e00246}, pmid = {34268454}, issn = {2398-9238}, mesh = {Adrenal Insufficiency/chemically induced/*drug therapy ; *COVID-19 ; Humans ; Immune Checkpoint Inhibitors/*adverse effects/therapeutic use ; Neoplasms/*drug therapy ; Pandemics ; }, abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) is currently a major pandemic challenge, and cancer patients are at a heightened risk of severity and mortality from this infection. In recent years, immune checkpoint inhibitor (ICI) use to treat multiple cancers has increased in oncology, but equally has raised the question of whether ICI therapy and its side-effects is harmful or beneficial during this pandemic.

METHODS: A combination of published literature in PubMed between January 2010 and December 2020, recommended guidelines in non-cancer patients, and clinical experience was utilized to outline recommendations on glucocorticoid timing and dosing regimens in ICI-treated patients presenting with AI during this COVID-19 pandemic.

RESULTS: The potential immune interaction between ICIs and COVID-19 require major consideration because these agents act at the intersection between effective cancer immunotherapy and increasing patient susceptibility, severity and complications from the SARS-CoV-2 sepsis. Furthermore, ICI use can induce autoimmune adrenal insufficiency (AI) that further increases infection susceptibility. Thus, ICI-treated cancer patients with AI may be at greater risk of COVID-19 infection. Glucocorticoids are the cornerstone for replacement therapy, and for treatment and mitigation of adrenal crisis and relief of mass effects in ICI-related hypophysitis. High-dose glucocorticoids have also been used with cytotoxic chemotherapy as part of cancer treatment, and iatrogenic AI may arise after glucocorticoid discontinuation that increases the risk of adrenal crisis. Furthermore, in patients who develop the "long COVID-19" syndrome, when to discontinue glucocorticoid therapy becomes crucial to avoid unnecessary prolongation of therapy and the development of iatrogenic hypercortisolemia.

CONCLUSION: During the COVID-19 pandemic, much of cancer care have been impacted and an important clinical question is how to optimally manage ICI-related AI during these unprecedented times. Herein, we suggest practical recommendations on the timing and dosing regimens of glucocorticoids in different clinical scenarios of ICI-treated cancer patients presenting with AI during this COVID-19 pandemic.}, } @article {pmid34266783, year = {2021}, author = {Burtey, S and Sallée, M}, title = {[Kidney damage in COVID-19].}, journal = {Nephrologie & therapeutique}, volume = {17}, number = {4}, pages = {203-207}, pmid = {34266783}, issn = {1872-9177}, mesh = {Acute Kidney Injury/*virology ; Biopsy ; COVID-19/*complications ; COVID-19 Vaccines/adverse effects ; Glomerulosclerosis, Focal Segmental/*virology ; Humans ; Kidney/pathology ; Kidney Tubular Necrosis, Acute/*virology ; }, abstract = {COVID-19 is a disease caused by the RNA virus SARS-CoV-2. It is characterised by an attack mainly affecting the respiratory system. There is renal involvement which is characterised by three main types of damage, acute tubular necrosis occurring in the most severe cases, proximal tubulopathy which is a prognostic marker of the disease and segmental and focal hyalinosis occurring in a genetically predisposed terrain. The pathophysiology of SARS-CoV-2 renal involvement is not yet defined. The direct role of the virus is debated, whereas the cytokine storm and the hypoxic and thrombotic complications seem more important. The long-term outcome of the renal damage appears to be quite good. Long-term follow-up will allow us to say whether the renal damage is part of the long COVID.}, } @article {pmid34265229, year = {2021}, author = {Aiyegbusi, OL and Hughes, SE and Turner, G and Rivera, SC and McMullan, C and Chandan, JS and Haroon, S and Price, G and Davies, EH and Nirantharakumar, K and Sapey, E and Calvert, MJ and , }, title = {Symptoms, complications and management of long COVID: a review.}, journal = {Journal of the Royal Society of Medicine}, volume = {114}, number = {9}, pages = {428-442}, pmid = {34265229}, issn = {1758-1095}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MR/L008335/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications/therapy ; Delivery of Health Care ; Diarrhea/etiology ; Employment ; Fatigue/etiology ; Headache/etiology ; Humans ; Mental Disorders/etiology ; Mental Health ; Pain/etiology ; *Quality of Life ; Respiratory Tract Diseases/etiology ; SARS-CoV-2 ; Sensation Disorders/etiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.}, } @article {pmid34262566, year = {2021}, author = {Fineschi, S}, title = {Case Report: Systemic Sclerosis After Covid-19 Infection.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {686699}, pmid = {34262566}, issn = {1664-3224}, mesh = {Autoantibodies/immunology ; Autoimmune Diseases/*etiology ; *Autoimmunity ; COVID-19/*complications/immunology/virology ; Calcium Channel Blockers/therapeutic use ; Follow-Up Studies ; Humans ; Lung Diseases, Interstitial/diagnostic imaging/etiology ; Male ; Middle Aged ; Proton Pump Inhibitors/therapeutic use ; Raynaud Disease/diagnosis/etiology ; SARS-CoV-2/*genetics ; Scleroderma, Systemic/drug therapy/*etiology ; Tomography, X-Ray Computed ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. The acute phase of the infection may in certain individuals be followed by another longer phase of disease (long COVID) of unknown etiology probably associated in certain cases with autoimmune activation. It has been shown that COVID-19 can trigger autoantibody production and in genetically predisposed patients may cause the onset or exacerbation of autoimmune diseases. We are reporting a case of mild COVID-19 infection complicated by autoantibody production and cutaneous and gastrointestinal symptoms and subsequently diagnosed with systemic sclerosis (SSc). A 47-year-old man with no history of any autoimmune diseases and in good health became sick together with his family on the 12th of November with mild symptoms: tiredness, fever, cough, and sore throat. Oropharyngeal swab for SARS-CoV-2 tested positive. He was isolated at home and did not require hospitalization. Three weeks later he presented with clinical manifestation compatible with suspicion of SSc. He briefly presented with skin rush, periorbital edema and conjunctivitis, vomiting, dysphagia, burning sensation in the skin, above all in the fingertips and around the mouth, puffy fingers, Raynaud's phenomenon, pain at the fingertip of the middle finger where a depressed area was noticed without a clear ulceration. ANA showed a strongly positive nucleolar pattern. Anti-PM/Scl 75 and PM/Scl 100 resulted positive. High-resolution computed tomography (HCRT) showed early stage of interstitial lung disease (ILD). The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical and radiological pictures according to the ACR/EULAR classification (scores: puffy finger, 2; ILD, 2; Raynaud's phenomenon, 3; SSc related antibodies, 3; total 10). There are several cases described in the medical literature of possible new onset of SLE after COVID-19 infection. This is the first case that describes a possible new onset of SSc. Conclusion: SARS-CoV-2 may trigger systemic sclerosis.}, } @article {pmid34262190, year = {2021}, author = {Lewis, D}, title = {Long COVID and kids: scientists race to find answers.}, journal = {Nature}, volume = {595}, number = {7868}, pages = {482-483}, pmid = {34262190}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Aged ; Anosmia/complications ; *Biomedical Research ; COVID-19/*complications/diagnosis/epidemiology ; Child ; Child, Preschool ; Chronic Disease/epidemiology ; Common Cold ; Fatigue/complications ; Headache/complications ; Humans ; Inflammation/complications ; Male ; Middle Aged ; Myalgia/complications ; *Pediatrics ; Physical Distancing ; Preprints as Topic ; *Research Personnel ; Risk Assessment ; Schools/organization & administration ; Sleep Initiation and Maintenance Disorders/complications ; Syndrome ; Uncertainty ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34257762, year = {2021}, author = {Okada, Y and Yoshimura, K and Toya, S and Tsuchimochi, M}, title = {Pathogenesis of taste impairment and salivary dysfunction in COVID-19 patients.}, journal = {The Japanese dental science review}, volume = {57}, number = {}, pages = {111-122}, pmid = {34257762}, issn = {1882-7616}, abstract = {Coronavirus disease 2019 (COVID-19) is a highly transmissible pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The characteristics of the disease include a broad range of symptoms from mild to serious to death, with mild pneumonia to acute respiratory distress syndrome and complications in extrapulmonary organs. Taste impairment and salivary dysfunction are common early symptoms in COVID-19 patients. The mouth is a significant entry route for SARS-COV-2, similar to the nose and eyes. The cells of the oral epithelium, taste buds, and minor and major salivary glands express cell entry factors for SARS-COV-2, such as ACE2, TMPRSS2, and Furin. We describe the occurrence of taste impairment and salivary dysfunction in COVID-19 patients and show immunohistochemical findings regarding the cell entry factors in the oral tissue. We review and describe the pathogeneses of taste impairment and salivary dysfunction. Treatment for the oral disease is also described. Recently, it was reported that some people experience persistent and prolonged taste impairment and salivary dysfunction, described as post-COVID-19 syndrome or long COVID-19, after the acute illness of the infection has healed. To resolve these problems, it is important to understand the pathogenesis of oral complications. Recently, important advances have been reported in the understanding of gustatory impairment and salivary dysfunction. Although some progress has been made, considerable effort is still required for in-depth elucidation of the pathogenesis.}, } @article {pmid34257426, year = {2021}, author = {Schmidt, C}, title = {COVID-19 long haulers.}, journal = {Nature biotechnology}, volume = {39}, number = {8}, pages = {908-913}, doi = {10.1038/s41587-021-00984-7}, pmid = {34257426}, issn = {1546-1696}, mesh = {Antiviral Agents/*therapeutic use ; COVID-19/*complications/physiopathology ; Drug Repositioning ; Humans ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; }, abstract = {With the risks of drug development prohibitive, repurposed or repositioned medicines appear the best hope against long-COVID, a condition that still raises many unanswered questions.}, } @article {pmid34256409, year = {2021}, author = {Simon, OJ and Menzler, K and Timmermann, L}, title = {[Update 2021: COVID-19 from the perspective of neurology].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {146}, number = {13-14}, pages = {918-923}, doi = {10.1055/a-1449-5098}, pmid = {34256409}, issn = {1439-4413}, mesh = {COVID-19/*complications ; Humans ; Nervous System Diseases/*complications/etiology ; *Neurology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurological complications, direct affection of neuronal structures in the course of infections with SARS-CoV-2 and long-term effects ("long COVID") are evident. This article aims to summarize and evaluate the current literature on this topic.}, } @article {pmid34255355, year = {2021}, author = {Kayaaslan, B and Eser, F and Kalem, AK and Kaya, G and Kaplan, B and Kacar, D and Hasanoglu, I and Coskun, B and Guner, R}, title = {Post-COVID syndrome: A single-center questionnaire study on 1007 participants recovered from COVID-19.}, journal = {Journal of medical virology}, volume = {93}, number = {12}, pages = {6566-6574}, pmid = {34255355}, issn = {1096-9071}, mesh = {Adolescent ; Adult ; COVID-19/*complications/epidemiology/etiology/pathology ; Fatigue/etiology ; Female ; Humans ; Male ; Middle Aged ; Myalgia/etiology ; Prevalence ; Prospective Studies ; Risk Factors ; Surveys and Questionnaires ; Weight Loss ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post recovery manifestations have become another concern in patients who have recovered from coronavirus disease 2019 (COVID-19). Numerous reports have shown that COVID-19 has a variety of long-term effects on almost all systems including respiratory, cardiovascular, gastrointestinal, neurological, psychiatric, and dermatological systems. We aimed to investigate the prevalence and characteristics of the post-COVID syndrome among COVID-19 survivors and to determine the factors associated with persistent symptoms. This prospective study enrolled in patients with COVID-19 followed in hospital or outpatient clinics in Ankara City Hospital. We performed a special questionnaire to inquire about the presence of persistent symptoms beyond 12 weeks from the first diagnosis. Demographic data, comorbid diseases, characteristics of acute COVID-19, presence of persistent symptoms by systems, and knowledge about outpatient clinic visits after recovery were assessed. Of a total of 1007 participants, 39.0% had at least one comorbidity, and 47.5% had persistent symptoms. Fatigue/easy fatigability, myalgia, and loss of weight were the most frequent persistent symptoms (overall 29.3%) followed by respiratory symptoms (25.4%). A total of 235 participants had visited outpatient clinics due to several reasons during the post-COVID-19 period, and 17 of them were hospitalized. Severe acute COVID-19, hospitalization, and presence of comorbidity were independent factors for the development of persistent symptoms. Fully understanding the spectrum of the post-COVID syndrome is essential for appropriate management of all its long-term effects. Our study once again underlined the fact that the prevalence of post-COVID syndrome is higher than expected and concerns many systems, and a multidisciplinary follow-up should be provided to COVID-19 survivors in the post recovery period.}, } @article {pmid34254725, year = {2021}, author = {Brüssow, H and Brüssow, L}, title = {Clinical evidence that the pandemic from 1889 to 1891 commonly called the Russian flu might have been an earlier coronavirus pandemic.}, journal = {Microbial biotechnology}, volume = {14}, number = {5}, pages = {1860-1870}, pmid = {34254725}, issn = {1751-7915}, mesh = {Aged ; Animals ; *COVID-19/complications ; Horses ; Humans ; *Influenza, Human/epidemiology ; Pandemics ; Russia ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Contemporary medical reports from Britain and Germany on patients suffering from a pandemic infection between 1889 and 1891, which was historically referred to as the Russian flu, share a number of characteristics with COVID-19. Most notable are aspects of multisystem affections comprising respiratory, gastrointestinal and neurological symptoms including loss of taste and smell perception; a protracted recovery resembling long covid and pathology observations of thrombosis in multiple organs, inflammation and rheumatic affections. As in COVID-19 and unlike in influenza, mortality was seen in elderly subjects while children were only weakly affected. Contemporary reports noted trans-species infection between pet animals or horses and humans, which would concur with a cross-infection by a broad host range bovine coronavirus dated by molecular clock arguments to an about 1890 cross-species infection event.}, } @article {pmid34249668, year = {2022}, author = {Kapoor, D and Verma, N and Gupta, N and Goyal, A}, title = {Post Viral Olfactory Dysfunction After SARS-CoV-2 Infection: Anticipated Post-pandemic Clinical Challenge.}, journal = {Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India}, volume = {74}, number = {Suppl 3}, pages = {4571-4578}, pmid = {34249668}, issn = {2231-3796}, abstract = {Persistent olfactory dysfunction (OD) is the second most common symptom of post coronavirus disease-19 (COVID-19) now being termed long-COVID. Its prevalence after recovery from COVID-19 is estimated to be 12% after nearly 6 months of follow-up. It thus becomes imperative for the treating clinicians to update themselves with the pathophysiology of this post COVID disability as well as the tools for diagnosis and the available treatment options. A systematic literature search was performed as per PRISMA guidelines in MEDLINE, Cochrane Library, LILACS, Google Scholar, ClinicalTrials.gov, and medRxiv databases. The keywords used were covid-19, Olfactory Disorders, Smell, Anosmia, PVOD, Post Viral Olfactory Disorders, post-covid and post haul. All articles were studied for definition, mechanism, diagnostic tests and treatment options for post COVID OD. 33 published articles and 8 ongoing trials were found relevant and included after full-text review. SARS-CoV-2 can cause conductive, neural and central OD. Olfactory evaluation can be done both subjectively (visual analogue scale) and objectively (Sniffin' sticks, Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test and modified Davidson's alcohol sniff test). They can be used to detect and follow-up patients. Despite several on-going clinical trials, the most reliable and advisable treatment option available till date is olfactory training.}, } @article {pmid34249236, year = {2021}, author = {Alqahtani, JS and Alghamdi, SM and Aldhahir, AM and Althobiani, M and Raya, RP and Oyelade, T}, title = {Thoracic imaging outcomes in COVID-19 survivors.}, journal = {World journal of radiology}, volume = {13}, number = {6}, pages = {149-156}, pmid = {34249236}, issn = {1949-8470}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic presents a significant global public health challenge. One in five individuals with COVID-19 presents with symptoms that last for weeks after hospital discharge, a condition termed "long COVID". Thus, efficient follow-up of patients is needed to assess the resolution of lung pathologies and systemic involvement. Thoracic imaging is multimodal and involves using different forms of waves to produce images of the organs within the thorax. In general, it includes chest X-ray, computed tomography, lung ultrasound and magnetic resonance imaging techniques. Such modalities have been useful in the diagnosis and prognosis of COVID-19. These tools have also allowed for the follow-up and assessment of long COVID. This review provides insights on the effectiveness of thoracic imaging techniques in the follow-up of COVID-19 survivors who had long COVID.}, } @article {pmid34248921, year = {2021}, author = {Proal, AD and VanElzakker, MB}, title = {Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {698169}, pmid = {34248921}, issn = {1664-302X}, abstract = {The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.}, } @article {pmid34245450, year = {2021}, author = {Scherlinger, M and Felten, R and Gallais, F and Nazon, C and Chatelus, E and Pijnenburg, L and Mengin, A and Gras, A and Vidailhet, P and Arnould-Michel, R and Bibi-Triki, S and Carapito, R and Trouillet-Assant, S and Perret, M and Belot, A and Bahram, S and Arnaud, L and Gottenberg, JE and Fafi-Kremer, S and Sibilia, J}, title = {Refining "Long-COVID" by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection.}, journal = {Infectious diseases and therapy}, volume = {10}, number = {3}, pages = {1747-1763}, pmid = {34245450}, issn = {2193-8229}, abstract = {INTRODUCTION: COVID-19 long-haulers, also decribed as having "long-COVID" or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied.

METHODS: In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group.

RESULTS: The median age was 40 [interquartile range: 35-54] years and 18 (60%) were female. At a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 [5-8] and 5 [2-6], respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively.

CONCLUSIONS: Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress.}, } @article {pmid34244323, year = {2021}, author = {Naeije, R and Caravita, S}, title = {Phenotyping long COVID.}, journal = {The European respiratory journal}, volume = {58}, number = {2}, pages = {}, pmid = {34244323}, issn = {1399-3003}, mesh = {*COVID-19/complications ; Humans ; Phenotype ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Patients who recover from an acute SARS-CoV-2 infection often present with persistent symptoms lasting for months. The cardiopulmonary exercise test profile of those with “long COVID” is suggestive of deconditioning with a tendency to hyperventilation. https://bit.ly/3y8n0Bt}, } @article {pmid34242539, year = {2023}, author = {Walsh-Messinger, J and Manis, H and Vrabec, A and Sizemore, J and Bishof, K and Debidda, M and Malaspina, D and Greenspan, N}, title = {The kids are not alright: A preliminary report of Post-COVID syndrome in university students.}, journal = {Journal of American college health : J of ACH}, volume = {71}, number = {5}, pages = {1367-1373}, pmid = {34242539}, issn = {1940-3208}, support = {R01 MH110418/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Middle Aged ; Humans ; *COVID-19/epidemiology ; SARS-CoV-2 ; Acute Disease ; Universities ; Students ; *Olfaction Disorders/epidemiology ; }, abstract = {OBJECTIVE: To investigate the prevalence and features of protracted COVID-19 symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness.

PARTICIPANTS: COVID-19 positive participants with symptoms ≥ 28 days (N = 22), herein referred to as post-COVID syndrome, were compared to those who fully recovered (N = 21) and those never diagnosed with the disease (N = 58).

METHODS: Students completed online study to earn research credit for class.

RESULTS: 51% of COVID-19 positive participants were classified with post-COVID syndrome. During acute illness, those with post-COVID syndrome experienced more chest pain, fatigue, fever, olfactory impairment, headaches, and diarrhea compared to fully recovered participants. They also reported more current exercise intolerance, dyspnea, chest pain, olfactory impairment, lymphadenopathy, gustatory impairment, and appetite loss than students who never contracted COVID-19.

CONCLUSIONS: Our results contradict the perception that this yet to be defined post-COVID syndrome predominantly affects middle-aged adults. Student health centers should closely monitor those who contract COVID-19 for lingering effects.}, } @article {pmid34241639, year = {2022}, author = {Frank, U and Frank, K}, title = {[COVID-19-New challenges in dysphagia and respiratory therapy].}, journal = {Der Nervenarzt}, volume = {93}, number = {2}, pages = {167-174}, pmid = {34241639}, issn = {1433-0407}, mesh = {*COVID-19/complications ; *Deglutition Disorders/diagnosis/therapy ; Humans ; Respiration, Artificial/*adverse effects ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) can lead to severe disease courses with multiple organ involvement, respiratory and neurological functional impairments. Swallowing disorders (dysphagia) in this patient group can result from primary damage to the central and peripheral neuronal swallowing network but also from the frequently prolonged intensive care treatment and mechanical ventilation. Clinical observations indicate persistence of dysphagia in post-acute COVID-19 syndrome (long COVID), so that these patients probably also need long-term interventions for rehabilitation of safe and sufficient oral feeding. Therefore, structured disease-specific monitoring of dysphagia symptoms should be integrated into the treatment of COVID-19 patients and respiratory therapy should be an essential part of dysphagia management to re-establish cough effectiveness and breathing-swallowing coordination. Challenges arise from necessary adjustments to established treatment standards to prevent infections. Furthermore, the selection and intensity of therapeutic measures have to be adapted to the capacities and the specific pathophysiology of COVID-19 and long COVID patients to prevent further functional deterioration.}, } @article {pmid34240374, year = {2021}, author = {Zeile, T}, title = {[Treating elderly geriatric patients right - some special aspects regarding sequential acute medical treatment and rehabilitation, rehabilitation and the new IPReG and long-Covid- rehabilitation].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {13}, pages = {48-50}, doi = {10.1007/s15006-021-0017-2}, pmid = {34240374}, issn = {1613-3560}, mesh = {Aged ; *COVID-19/complications ; Geriatric Assessment ; *Health Services for the Aged ; Humans ; Patient Rights ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34237471, year = {2021}, author = {Lui, DTW and Lee, CH and Chow, WS and Lee, ACH and Tam, AR and Pang, P and Ho, TY and Fong, CHY and Law, CY and Leung, EKH and To, KKW and Tan, KCB and Woo, YC and Lam, CW and Hung, IFN and Lam, KSL}, title = {Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {27}, number = {9}, pages = {894-902}, pmid = {34237471}, issn = {1530-891X}, mesh = {Adult ; *Autoimmunity ; *COVID-19/complications ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Thyroid Gland ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: Post-acute sequelae of coronavirus disease 2019 (COVID-19) or long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC.

METHODS: We included consecutive adults without a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up.

RESULTS: In total, 204 patients (median age, 55.0 years; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043).

CONCLUSION: LC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.}, } @article {pmid34237419, year = {2021}, author = {Zacharias, H and Dubey, S and Koduri, G and D'Cruz, D}, title = {Rheumatological complications of Covid 19.}, journal = {Autoimmunity reviews}, volume = {20}, number = {9}, pages = {102883}, pmid = {34237419}, issn = {1873-0183}, mesh = {Autoimmunity ; *COVID-19/complications ; Humans ; *Rheumatic Diseases ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: COVID-19 has caused unprecedented hardships in the 21st century with more than 150 million infections. Various immunological phenomena have been described during the course of the infection, and this infection has also triggered autoimmunity. Rheumatological illnesses have been described following resolution of the acute infection; hence we sought to conduct a review of the rheumatological complications of COVID-19.

METHODS: We conducted a literature search for articles relating to sequelae of COVID-19 from Jan 2020 to 30th April 2021.

RESULTS: We found a number of reports of inflammatory arthritis after SARS-CoV-2 infection. SLE and renal disease have been described, and vasculitis also appears to be a common complication. Rhabdomyolysis and myositis has also been reported in a number of patients. We also found some evidence of large vessel vasculitis in 'long COVID' patients.

CONCLUSIONS: This review highlights a number of important complications such as inflammatory arthritis, lupus-like disease, myostis and vasculitis following SARS-CoV-2 infection.}, } @article {pmid34237305, year = {2021}, author = {Hoffer, EP}, title = {Long COVID: Does It Exist? What Is It? We Can We Do For Sufferers?.}, journal = {The American journal of medicine}, volume = {134}, number = {11}, pages = {1310-1311}, pmid = {34237305}, issn = {1555-7162}, mesh = {Anosmia/physiopathology ; COVID-19/*complications/physiopathology/rehabilitation ; Cognitive Dysfunction/physiopathology ; Critical Illness ; Dysgeusia/physiopathology ; Dyspnea/physiopathology ; Exercise Therapy ; Fatigue/physiopathology ; Humans ; SARS-CoV-2 ; Severity of Illness Index ; Sleep Initiation and Maintenance Disorders/physiopathology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34236922, year = {2021}, author = {Brimson, JM and Prasanth, MI and Malar, DS and Brimson, S and Thitilertdecha, P and Tencomnao, T}, title = {Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy.}, journal = {Expert opinion on therapeutic targets}, volume = {25}, number = {6}, pages = {435-449}, pmid = {34236922}, issn = {1744-7631}, mesh = {Antiviral Agents/*therapeutic use ; *Autophagy ; COVID-19/mortality/virology ; Hospitalization/*statistics & numerical data ; Humans ; Receptors, sigma/*physiology ; SARS-CoV-2/isolation & purification ; *COVID-19 Drug Treatment ; Sigma-1 Receptor ; }, abstract = {Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.}, } @article {pmid34234251, year = {2021}, author = {Barizien, N and Le Guen, M and Russel, S and Touche, P and Huang, F and Vallée, A}, title = {Clinical characterization of dysautonomia in long COVID-19 patients.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {14042}, pmid = {34234251}, issn = {2045-2322}, mesh = {Adult ; COVID-19/*complications ; Fatigue/complications ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Primary Dysautonomias/*complications/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Increasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as "long COVID" infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed (p = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants (p = 0.109). No difference over time was observed between the two groups of long COVID-19 participants (p = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia. Trial registration: The study was approved by the Foch IRB: IRB00012437 (Approval Number: 20-12-02) on December 16, 2020.}, } @article {pmid34234065, year = {2021}, author = {Chopra, N and Chowdhury, M and Singh, AK and Ma, K and Kumar, A and Ranjan, P and Desai, D and Wig, N}, title = {Clinical predictors of long COVID-19 and phenotypes of mild COVID-19 at a tertiary care centre in India.}, journal = {Drug discoveries & therapeutics}, volume = {15}, number = {3}, pages = {156-161}, doi = {10.5582/ddt.2021.01014}, pmid = {34234065}, issn = {1881-784X}, mesh = {Adult ; COVID-19/epidemiology/*physiopathology/virology ; Female ; Follow-Up Studies ; Humans ; India/epidemiology ; Male ; Middle Aged ; Patient Discharge ; SARS-CoV-2/isolation & purification ; Tertiary Care Centers/*organization & administration ; Time and Motion Studies ; Young Adult ; }, abstract = {A variable proportion of patients develop persistent/prolonged symptoms of Coronavirus Disease 2019 (COVID-19) infection (long COVID). We aimed to study the clinical predictors of persistent symptoms in patients with mild COVID-19 at 30 days post discharge (long COVID-19). We also tried to identify symptom clusters among mild COVID-19 patients. Fifty-seven patients admitted at a tertiary care centre after a positive RT-PCR report over a period of 2 months, were enrolled in the study. Details of presentation, history of illness, laboratory investigations and disease outcomes were recorded from documented medical records and discharge slip. The patients were contacted (telephonically) at 30 days after discharge and enquired regarding persistent symptoms, if any. Follow up data at 30 days post-discharge was available for 53 patients. Among them, the most common persistent symptom was fatigue (22.6%), followed by cough (9.4%) and myalgias (7.5%). There was a significant association of persistent symptoms with diarrhoea at presentation [OR 14.26 (95% CI 2.30-142.47; p = 0.009] and gap between symptom onset and admission [OR 1.40 (95% CI 1.08-1.93; p = 0.020] on multivariate logistic regression analysis. On cluster analysis, three phenotypes of mild COVID-19 were identified, which may have implications on monitoring and management. There appears to be a positive association of diarrhoea as a presenting manifestation and gap between symptom onset and admission with the persistence of symptoms classified as long COVID-19, even in mild illness. We also identified multiple phenotypes of mild COVID-19 illness, which warrant further exploration.}, } @article {pmid34230579, year = {2021}, author = {Clark, S and Morris, M and Lomax, N and Birkin, M}, title = {Can a data driven obesity classification system identify those at risk of severe COVID-19 in the UK Biobank cohort study?.}, journal = {International journal of obesity (2005)}, volume = {45}, number = {10}, pages = {2281-2285}, pmid = {34230579}, issn = {1476-5497}, support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Aged ; Aged, 80 and over ; *COVID-19/diagnosis/epidemiology ; Cohort Studies ; Female ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; *Obesity/classification/epidemiology ; Risk Factors ; United Kingdom/epidemiology ; }, abstract = {COVID-19 is a disease that has been shown to have outcomes that vary by certain socio-demographic and socio-economic groups. It is increasingly important that an understanding of these outcomes should be derived not from the consideration of one aspect, but by a more multi-faceted understanding of the individual. In this study use is made of a recent obesity driven classification of participants in the United Kingdom Biobank (UKB) to identify trends in COVID-19 outcomes. This classification is informed by a recently created obesity systems map, and the COVID-19 outcomes are: undertaking a test, a positive test, hospitalisation and mortality. It is demonstrated that the classification is able to identify meaningful differentials in these outcomes. This more holistic approach is recommended for identification and prioritisation of COVID-19 risk and possible long-COVID determination.}, } @article {pmid34223884, year = {2022}, author = {Seeßle, J and Waterboer, T and Hippchen, T and Simon, J and Kirchner, M and Lim, A and Müller, B and Merle, U}, title = {Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {74}, number = {7}, pages = {1191-1198}, pmid = {34223884}, issn = {1537-6591}, mesh = {Adult ; Antibodies, Viral ; *COVID-19/complications ; Female ; Follow-Up Studies ; Humans ; Male ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long COVID is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of patients with COVID-19 prospectively.

METHODS: Patients were included at 5 months after acute COVID-19 in this prospective, noninterventional, follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n = 96; 32.3% hospitalized, 55.2% females) were included in this analysis of symptoms, quality of life (based on an SF-12 survey), laboratory parameters including antinuclear antibodies (ANAs), and SARS-CoV-2 antibody levels.

RESULTS: At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnea (37.5%), and problems with concentration (39.6%), finding words (32.3%), and sleeping (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥1:160 in 43.6% of patients at 12 months post-COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥1:160 versus <1:160. Compared with patients without symptoms, patients with ≥1 long-COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2 antibody levels but had a significantly reduced physical and mental life quality compared with patients without symptoms.

CONCLUSIONS: Neurocognitive long-COVID symptoms can persist ≥1 year after COVID-19 symptom onset and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in etiology of long COVID.}, } @article {pmid34219856, year = {2021}, author = {Le Page, M and Thomson, H and Vaughan, A and Wilson, C}, title = {Getting to grips with long covid.}, journal = {New scientist (1971)}, volume = {250}, number = {3340}, pages = {10-13}, doi = {10.1016/S0262-4079(21)01081-2}, pmid = {34219856}, issn = {0262-4079}, abstract = {Millions of people worldwide are experiencing lasting symptoms from covid-19. Michael Le Page, Helen Thomson, Adam Vaughan and Clare Wilson report on what we do - and don't - know so far.}, } @article {pmid34215639, year = {2021}, author = {Agarwala, SR and Vijayvargiya, M and Pandey, P}, title = {Avascular necrosis as a part of 'long COVID-19'.}, journal = {BMJ case reports}, volume = {14}, number = {7}, pages = {}, pmid = {34215639}, issn = {1757-790X}, mesh = {*COVID-19/complications ; COVID-19 Testing ; *Femur Head Necrosis ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {'Long COVID-19' can affect different body systems. At present, avascular necrosis (AVN) as a sequalae of 'long COVID-19' has yet not been documented. By large-scale use of life-saving corticosteroids in COVID-19 cases, we anticipate that there will be a resurgence of AVN cases. We report a series of three cases in which patients developed AVN of the femoral head after being treated for COVID-19 infection. The mean dose of prednisolone used in these cases was 758 mg (400-1250 mg), which is less than the mean cumulative dose of around 2000 mg steroid, documented in the literature as causative for AVN. Patients were symptomatic and developed early AVN presentation at a mean of 58 days after COVID-19 diagnosis as compared with the literature which shows that it generally takes 6 months to 1 year to develop AVN post steroid exposure.}, } @article {pmid34215626, year = {2021}, author = {Wise, J}, title = {Covid-19: Long covid cases are underreported in GP records, research suggests.}, journal = {BMJ (Clinical research ed.)}, volume = {374}, number = {}, pages = {n1685}, doi = {10.1136/bmj.n1685}, pmid = {34215626}, issn = {1756-1833}, } @article {pmid34215435, year = {2021}, author = {Horn, M and Fovet, T and Vaiva, G and D'Hondt, F and Amad, A}, title = {Somatic symptom disorders and long COVID: A critical but overlooked topic.}, journal = {General hospital psychiatry}, volume = {72}, number = {}, pages = {149-150}, pmid = {34215435}, issn = {1873-7714}, mesh = {*COVID-19/complications ; Humans ; *Medically Unexplained Symptoms ; *Mental Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34210789, year = {2022}, author = {Osmanov, IM and Spiridonova, E and Bobkova, P and Gamirova, A and Shikhaleva, A and Andreeva, M and Blyuss, O and El-Taravi, Y and DunnGalvin, A and Comberiati, P and Peroni, DG and Apfelbacher, C and Genuneit, J and Mazankova, L and Miroshina, A and Chistyakova, E and Samitova, E and Borzakova, S and Bondarenko, E and Korsunskiy, AA and Konova, I and Hanson, SW and Carson, G and Sigfrid, L and Scott, JT and Greenhawt, M and Whittaker, EA and Garralda, E and Swann, OV and Buonsenso, D and Nicholls, DE and Simpson, F and Jones, C and Semple, MG and Warner, JO and Vos, T and Olliaro, P and Munblit, D and , }, title = {Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study.}, journal = {The European respiratory journal}, volume = {59}, number = {2}, pages = {}, pmid = {34210789}, issn = {1399-3003}, support = {MC_PC_15001/MRC_/Medical Research Council/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_PC_19059/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Aged ; *COVID-19 ; Child ; Child, Hospitalized ; Female ; Follow-Up Studies ; Humans ; Prospective Studies ; Risk Factors ; SARS-CoV-2 ; }, abstract = {BACKGROUND: The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 and associated risk factors.

METHODS: This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved.

RESULTS: 518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67).

CONCLUSIONS: A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.}, } @article {pmid34209705, year = {2021}, author = {Lee, CCE and Ali, K and Connell, D and Mordi, IR and George, J and Lang, EM and Lang, CC}, title = {COVID-19-Associated Cardiovascular Complications.}, journal = {Diseases (Basel, Switzerland)}, volume = {9}, number = {3}, pages = {}, pmid = {34209705}, issn = {2079-9721}, abstract = {Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg[9]-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications.}, } @article {pmid34207876, year = {2021}, author = {Paneroni, M and Pasini, E and Vitacca, M and Scalvini, S and Comini, L and Pedrinolla, A and Venturelli, M}, title = {Altered Vascular Endothelium-Dependent Responsiveness in Frail Elderly Patients Recovering from COVID-19 Pneumonia: Preliminary Evidence.}, journal = {Journal of clinical medicine}, volume = {10}, number = {12}, pages = {}, pmid = {34207876}, issn = {2077-0383}, abstract = {We evaluated vascular dysfunction with the single passive leg movement test (sPLM) in 22 frail elderly patients at 84 + 31 days after hospitalization for COVID-19 pneumonia, compared to 22 age-, sex- and comorbidity-matched controls (CTRL). At rest, all COVID-19 patients were in stable clinical condition without severe comorbidities. Patients (aged 72 ± 6 years, 73% male) had moderate disability (Barthel index score 77 ± 26), hypoxemia and normocapnia at arterial blood gas analysis and mild pulmonary restriction at spirometry. Values of circulating markers of inflammation (C-reactive protein: CRP; erythrocyte sedimentation rate: ESR) and coagulation (D-dimer) were: 27.13 ± 37.52 mg/dL, 64.24 ± 32.37 mm/1 h and 1043 ± 729 ng/mL, respectively. At rest, femoral artery diameter was similar in COVID-19 and CTRL (p = 0.16). On the contrary, COVID-19 infection deeply impacted blood velocity (p = 0.001) and femoral blood flow (p < 0.0001). After sPLM, peak femoral blood flow was dramatically reduced in COVID-19 compared to CTRL (p = 0.001), as was blood flow ∆peak (p = 0.05) and the area under the curve (p < 0.0001). This altered vascular responsiveness could be one of the unknown components of long COVID-19 syndrome leading to fatigue, changes in muscle metabolism and fibers' composition, exercise intolerance and increased cardiovascular risk. Impact of specific treatments, such as exercise training, dietary supplements or drugs, should be evaluated.}, } @article {pmid34205086, year = {2021}, author = {Delbressine, JM and Machado, FVC and Goërtz, YMJ and Van Herck, M and Meys, R and Houben-Wilke, S and Burtin, C and Franssen, FME and Spies, Y and Vijlbrief, H and van 't Hul, AJ and Janssen, DJA and Spruit, MA and Vaes, AW}, title = {The Impact of Post-COVID-19 Syndrome on Self-Reported Physical Activity.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {11}, pages = {}, pmid = {34205086}, issn = {1660-4601}, mesh = {Activities of Daily Living ; *COVID-19/complications ; COVID-19 Testing ; Exercise ; Female ; Humans ; Male ; Middle Aged ; *Quality of Life ; SARS-CoV-2 ; Self Report ; Post-Acute COVID-19 Syndrome ; }, abstract = {Background: A subgroup of patients recovering from COVID-19 experience persistent symptoms, decreased quality of life, increased dependency on others for personal care and impaired performance of activities of daily living. However, the long-term effects of COVID-19 on physical activity (PA) in this subgroup of patients with persistent symptoms remain unclear. Methods: Demographics, self-reported average time spent walking per week, as well as participation in activities pre-COVID-19 and after three and six months of follow-up were assessed in members of online long-COVID-19 peer support groups. Results: Two hundred thirty-nine patients with a confirmed COVID-19 diagnosis were included (83% women, median (IQR) age: 50 (39-56) years). Patients reported a significantly decreased weekly walking time after three months of follow-up (three months: 60 (15-120) min. vs. pre-COVID-19: 120 (60-240) min./week; p < 0.05). Six months after the onset of symptoms walking time was still significantly lower compared to pre-COVID-19 but significantly increased compared to three months of follow-up (three months: 60 (15-120) min. vs. six months: 90 (30-150) min.; p < 0.05). Conclusions: Patients who experience persistent symptoms after COVID-19 may still demonstrate a significantly decreased walking time six months after the onset of symptoms. More research is needed to investigate long-term consequences and possible treatment options to guide patients during the recovery fromCOVID-19.}, } @article {pmid34204243, year = {2021}, author = {Gold, JE and Okyay, RA and Licht, WE and Hurley, DJ}, title = {Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34204243}, issn = {2076-0817}, abstract = {Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein-Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher's exact test). A similar ratio was observed in a secondary group of 18 subjects 21-90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.}, } @article {pmid34192289, year = {2021}, author = {Dixit, NM and Churchill, A and Nsair, A and Hsu, JJ}, title = {Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?.}, journal = {American heart journal plus : cardiology research and practice}, volume = {5}, number = {}, pages = {100025}, pmid = {34192289}, issn = {2666-6022}, abstract = {Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.}, } @article {pmid34192271, year = {2021}, author = {Mondelli, V and Pariante, CM}, title = {What can neuroimmunology teach us about the symptoms of long-COVID?.}, journal = {Oxford open immunology}, volume = {2}, number = {1}, pages = {iqab004}, pmid = {34192271}, issn = {2633-6960}, support = {/WT_/Wellcome Trust/United Kingdom ; MRF_MRF-160-0005-ELP-MONDE/MRF/MRF/United Kingdom ; }, abstract = {Long-Coronavirus Disease (Long-COVID) is becoming increasingly recognized due to the persistence of symptoms such as profound fatigue, neurocognitive difficulties, muscle pains and weaknesses and depression, which would last beyond 3-12 weeks following infection with SARS-CoV-2. These particular symptoms have been extensively observed and studied in the context of previous psychoneuroimmunology research. In this short commentary, we discuss how previous neuroimmunology studies could help us to better understand pathways behind the development of these prolonged symptoms. Various mechanisms, including viral neuroinvasion, glial cells activation, neurogenesis, oxidative stress have been shown to explain these symptoms in the context of other disorders. Previous neuroimmunology findings could represent helpful pointers for future research on long-COVID symptoms and suggest potential management strategies for patients suffering with long-COVID.}, } @article {pmid34188995, year = {2021}, author = {Singh, R and Gaziano, D}, title = {Functional and Radiological Improvement in a COVID-19 Pneumonia Patient Treated With Steroids.}, journal = {Cureus}, volume = {13}, number = {5}, pages = {e15257}, pmid = {34188995}, issn = {2168-8184}, abstract = {Like its predecessors, coronavirus disease 2019 (COVID-19) can lead to long-term health-related consequences in a significant segment of the afflicted population. Although the medical community has developed multiple vaccines by now, COVID-19 has affected over 100 million individuals worldwide and will infect millions more before vaccines can be effectively distributed on a global scale. Additionally, it seems probable that another outbreak caused by a coronavirus may occur in the future, given that this is the third outbreak caused by a coronavirus in recent history. In light of this, the medical community must develop reliable methods of curtailing long-term sequelae of coronaviruses, and the use of corticosteroids in affected patients may be vital for this purpose. In this report, we present a case of progressive dyspnea caused by COVID-19 pneumonia; the patient was treated with a short course of oral corticosteroids, and subsequently showed marked improvement of the dyspnea with corresponding improvements on chest CT.}, } @article {pmid34186367, year = {2021}, author = {Fernández-de-Las-Peñas, C and Florencio, LL and Gómez-Mayordomo, V and Cuadrado, ML and Palacios-Ceña, D and Raveendran, AV}, title = {Proposed integrative model for post-COVID symptoms.}, journal = {Diabetes & metabolic syndrome}, volume = {15}, number = {4}, pages = {102159}, pmid = {34186367}, issn = {1878-0334}, mesh = {COVID-19/*complications/etiology/pathology/transmission/virology ; Hospitalization/*statistics & numerical data ; Humans ; *Models, Statistical ; SARS-CoV-2/*isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND AIMS: To propose an integrative model for post-COVID symptoms by considering the absence/presence of previous symptomatology.

METHODS: We searched different databases for original articles and reviews on post-COVID symptoms.

RESULTS: The first consideration is to define which symptoms are of "new-onset" (symptoms never experienced by a patient before COVID-19 and experienced the first time after) and which symptoms are "exacerbated" (symptoms experienced by a patient prior to COVID-19 but aggravated later) after infection. The second consideration includes defining "persistent" (symptoms experienced at the acute phase and continuing after without remission period) and "delayed-onset" (symptoms not experienced at the acute phase of the infection but appearing after a "latency period"). This model integrates predisposing individual factors, biological factors associated to the severity of disease, hospitalization/treatment factors, and outbreak surrounding factors which may promote post-COVID.

CONCLUSION: Since current literature on post-COVID is heterogeneous, this integrative model could help to a better characterization of long-COVID.}, } @article {pmid34185758, year = {2021}, author = {Sancak, B and Kılıç, C}, title = {A Psychiatrist's Own Experience of Long Covid: Looking Beyond the Psychosomatic Perspective.}, journal = {Psychiatria Danubina}, volume = {33}, number = {2}, pages = {250}, pmid = {34185758}, issn = {0353-5053}, mesh = {*COVID-19/complications ; Humans ; *Psychiatry ; Psychophysiologic Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34181102, year = {2021}, author = {Moghimi, N and Di Napoli, M and Biller, J and Siegler, JE and Shekhar, R and McCullough, LD and Harkins, MS and Hong, E and Alaouieh, DA and Mansueto, G and Divani, AA}, title = {The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.}, journal = {Current neurology and neuroscience reports}, volume = {21}, number = {9}, pages = {44}, pmid = {34181102}, issn = {1534-6293}, mesh = {Brain ; *COVID-19/complications ; Humans ; *SARS-CoV-2 ; United States ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature.

RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.}, } @article {pmid34175976, year = {2022}, author = {Scala, MR and Spennato, P and Cicala, D and Piccolo, V and Varone, A and Cinalli, G}, title = {Malignant cerebral infarction associated with COVID-19 in a child.}, journal = {Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery}, volume = {38}, number = {2}, pages = {441-445}, pmid = {34175976}, issn = {1433-0350}, mesh = {*Brain Ischemia ; *COVID-19/complications ; Cerebral Infarction/complications/diagnostic imaging ; Child ; *Decompressive Craniectomy ; Humans ; Infarction, Middle Cerebral Artery/surgery ; SARS-CoV-2 ; *Stroke/surgery ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; }, abstract = {Neurological manifestations, such as encephalitis, meningitis, ischemic, and hemorrhagic strokes, are reported with increasing frequency in patients affected by Coronavirus disease 2019 (COVID-19). In children, acute ischemic stroke is usually multifactorial: viral infection is an important precipitating factor for stroke. We present a case of a child with serological evidence of SARS-CoV-2 infection whose onset was a massive right cerebral artery ischemia that led to a malignant cerebral infarction. The patient underwent a life-saving decompressive hemicraniectomy, with good functional recovery, except for residual hemiplegia. During rehabilitation, the patient also developed a lower extremity peripheral nerve neuropathy, likely related to a long-Covid syndrome.}, } @article {pmid34175230, year = {2021}, author = {Komaroff, AL and Lipkin, WI}, title = {Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.}, journal = {Trends in molecular medicine}, volume = {27}, number = {9}, pages = {895-906}, pmid = {34175230}, issn = {1471-499X}, support = {U54 AI138370/AI/NIAID NIH HHS/United States ; }, mesh = {COVID-19/*complications/etiology/physiopathology ; Energy Metabolism ; Fatigue Syndrome, Chronic/*etiology/physiopathology ; Gastrointestinal Microbiome ; Humans ; Nervous System/physiopathology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.}, } @article {pmid34172475, year = {2021}, author = {Lokugamage, AU and Simpson, FK and Chew-Graham, CA}, title = {Patient commentary: How power imbalances in the narratives, research, and publications around long covid can harm patients.}, journal = {BMJ (Clinical research ed.)}, volume = {373}, number = {}, pages = {n1579}, doi = {10.1136/bmj.n1579}, pmid = {34172475}, issn = {1756-1833}, } @article {pmid34171458, year = {2021}, author = {Ramadan, MS and Bertolino, L and Zampino, R and Durante-Mangoni, E and , }, title = {Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {9}, pages = {1250-1261}, pmid = {34171458}, issn = {1469-0691}, mesh = {Adult ; COVID-19/complications/*diagnosis ; COVID-19 Nucleic Acid Testing ; Echocardiography ; Electrocardiography ; Heart Diseases/*epidemiology/etiology ; Humans ; Magnetic Resonance Imaging, Cine ; SARS-CoV-2/genetics/*isolation & purification ; }, abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.

OBJECTIVES: To assess the range of cardiac sequelae after COVID-19 recovery.

DATA SOURCES: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021).

STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies, case reports and case series.

PARTICIPANTS: Adult patients assessed for cardiac manifestations after COVID-19 recovery.

EXPOSURE: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR.

METHODS: Systematic review.

RESULTS: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1-180 days). Common short-term cardiac abnormalities (<3 months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3-6 months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7-3.2) of developing heart failure, arrythmias and myocardial infarction.

CONCLUSIONS: COVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.}, } @article {pmid34170086, year = {2021}, author = {Richter, D and Guasti, L and Koehler, F and Squizzato, A and Nistri, S and Christodorescu, R and Dievart, F and Gaudio, G and Asteggiano, R and Ferrini, M}, title = {Late phase of COVID-19 pandemic in General Cardiology. A position paper of the ESC Council for Cardiology Practice.}, journal = {ESC heart failure}, volume = {8}, number = {5}, pages = {3483-3494}, pmid = {34170086}, issn = {2055-5822}, mesh = {*COVID-19/complications ; *Cardiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID-19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID-19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a 'long COVID-19' illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a 'post-COVID' patient during follow-up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID-19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post-COVID patient and how to integrate in our standard of care the new information on COVID-19, possibly in a multidisciplinary view. Dealing with the increased COVID-associated CV risk burden and becoming acquainted with potential new e-cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.}, } @article {pmid34163217, year = {2021}, author = {Garg, M and Maralakunte, M and Garg, S and Dhooria, S and Sehgal, I and Bhalla, AS and Vijayvergiya, R and Grover, S and Bhatia, V and Jagia, P and Bhalla, A and Suri, V and Goyal, M and Agarwal, R and Puri, GD and Sandhu, MS}, title = {The Conundrum of 'Long-COVID-19': A Narrative Review.}, journal = {International journal of general medicine}, volume = {14}, number = {}, pages = {2491-2506}, pmid = {34163217}, issn = {1178-7074}, abstract = {COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate long-term consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multi-disciplinary clinics, and rehabilitation centers.}, } @article {pmid34163090, year = {2021}, author = {Blomberg, B and Mohn, KG and Brokstad, KA and Zhou, F and Linchausen, DW and Hansen, BA and Lartey, S and Onyango, TB and Kuwelker, K and Sævik, M and Bartsch, H and Tøndel, C and Kittang, BR and , and Cox, RJ and Langeland, N}, title = {Long COVID in a prospective cohort of home-isolated patients.}, journal = {Nature medicine}, volume = {27}, number = {9}, pages = {1607-1613}, pmid = {34163090}, issn = {1546-170X}, mesh = {Adolescent ; Adult ; Ageusia/virology ; Anosmia/virology ; Antibodies, Viral/*blood ; COVID-19/*complications/*pathology ; Child ; Child, Preschool ; Cognitive Dysfunction/*virology ; Dyspnea/*virology ; Fatigue/*virology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Norway ; Patient Isolation ; Prospective Studies ; SARS-CoV-2 ; Severity of Illness Index ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients-247 home-isolated and 65 hospitalized-comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.}, } @article {pmid34162913, year = {2021}, author = {Bliddal, S and Banasik, K and Pedersen, OB and Nissen, J and Cantwell, L and Schwinn, M and Tulstrup, M and Westergaard, D and Ullum, H and Brunak, S and Tommerup, N and Feenstra, B and Geller, F and Ostrowski, SR and Grønbæk, K and Nielsen, CH and Nielsen, SD and Feldt-Rasmussen, U}, title = {Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13153}, pmid = {34162913}, issn = {2045-2322}, support = {2020-0178//Sygesikring Danmark/ ; NNF14CC0001//Novo Nordisk Foundation/ ; NNF17OC0027594//Novo Nordisk Foundation/ ; Denmark//Novo Nordisk Foundation/ ; 0216-00014B//Independent Research Fund Denmark/ ; Denmark//Independent Research Fund/ ; }, mesh = {Acute Disease ; Adult ; Body Mass Index ; COVID-19/complications/diagnosis/*physiopathology ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Risk Factors ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {Reports of persistent symptoms after hospitalization with COVID-19 have raised concern of a "long COVID" syndrome. This study aimed at determining the prevalence of and risk factors for acute and persistent symptoms in non-hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19. We conducted a cohort study of non-hospitalized participants identified via the Danish Civil Registration System with a SARS-CoV-2-positive PCR-test and available biobank samples. Participants received a digital questionnaire on demographics and COVID-19-related symptoms. Persistent symptoms: symptoms > 4 weeks (in sensitivity analyses > 12 weeks). We included 445 participants, of whom 34% were asymptomatic. Most common acute symptoms were fatigue, headache, and sneezing, while fatigue and reduced smell and taste were most severe. Persistent symptoms, most commonly fatigue and memory and concentration difficulties, were reported by 36% of 198 symptomatic participants with follow-up > 4 weeks. Risk factors for persistent symptoms included female sex (women 44% vs. men 24%, odds ratio 2.7, 95% CI 1.4-5.1, p = 0.003) and BMI (odds ratio 1.1, 95% CI 1.0-1.2, p = 0.001). In conclusion, among non-hospitalized PCR-confirmed COVID-19 patients one third were asymptomatic while one third of symptomatic participants had persistent symptoms illustrating the heterogeneity of disease presentation. These findings should be considered in health care planning and policy making related to COVID-19.}, } @article {pmid34162532, year = {2021}, author = {Newman, M}, title = {Chronic fatigue syndrome and long covid: moving beyond the controversy.}, journal = {BMJ (Clinical research ed.)}, volume = {373}, number = {}, pages = {n1559}, doi = {10.1136/bmj.n1559}, pmid = {34162532}, issn = {1756-1833}, } @article {pmid34155207, year = {2021}, author = {Gassen, NC and Papies, J and Bajaj, T and Emanuel, J and Dethloff, F and Chua, RL and Trimpert, J and Heinemann, N and Niemeyer, C and Weege, F and Hönzke, K and Aschman, T and Heinz, DE and Weckmann, K and Ebert, T and Zellner, A and Lennarz, M and Wyler, E and Schroeder, S and Richter, A and Niemeyer, D and Hoffmann, K and Meyer, TF and Heppner, FL and Corman, VM and Landthaler, M and Hocke, AC and Morkel, M and Osterrieder, N and Conrad, C and Eils, R and Radbruch, H and Giavalisco, P and Drosten, C and Müller, MA}, title = {SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3818}, pmid = {34155207}, issn = {2041-1723}, mesh = {Animals ; Antinematodal Agents/pharmacology ; Autophagosomes/metabolism ; Autophagy ; Autophagy-Related Proteins/metabolism ; COVID-19/*metabolism/pathology/*virology ; Cells, Cultured ; Chlorocebus aethiops ; Cricetinae ; Disease Models, Animal ; Humans ; Lung/metabolism/pathology/virology ; Metabolome ; Niclosamide/pharmacology ; Organoids ; SARS-CoV-2/isolation & purification/*metabolism ; Spermidine/pharmacology ; Spermine/pharmacology ; COVID-19 Drug Treatment ; }, abstract = {Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC50 values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.}, } @article {pmid34153235, year = {2021}, author = {Burke, MJ and Del Rio, C}, title = {Long COVID has exposed medicine's blind-spot.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {8}, pages = {1062-1064}, pmid = {34153235}, issn = {1474-4457}, mesh = {COVID-19/*complications/epidemiology/therapy ; Humans ; SARS-CoV-2/physiology ; Symptom Assessment ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34151246, year = {2021}, author = {Touyz, RM and Boyd, MOE and Guzik, T and Padmanabhan, S and McCallum, L and Delles, C and Mark, PB and Petrie, JR and Rios, F and Montezano, AC and Sykes, R and Berry, C}, title = {Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19.}, journal = {CJC open}, volume = {3}, number = {10}, pages = {1257-1272}, pmid = {34151246}, issn = {2589-790X}, support = {CH/12/4/29762/BHF_/British Heart Foundation/United Kingdom ; MR/M016560/1/MRC_/Medical Research Council/United Kingdom ; MR/N003403/1/MRC_/Medical Research Council/United Kingdom ; PG/17/25/32884/BHF_/British Heart Foundation/United Kingdom ; }, abstract = {The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).}, } @article {pmid34148674, year = {2021}, author = {Ranque, B}, title = {[To call a spade a spade].}, journal = {La Revue de medecine interne}, volume = {42}, number = {7}, pages = {449-451}, pmid = {34148674}, issn = {1768-3122}, mesh = {COVID-19/*complications/diagnosis ; Diagnosis, Differential ; Fatigue/*etiology ; Humans ; *Symptom Assessment ; Terminology as Topic ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34143277, year = {2022}, author = {Hugon, J and Msika, EF and Queneau, M and Farid, K and Paquet, C}, title = {Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex.}, journal = {Journal of neurology}, volume = {269}, number = {1}, pages = {44-46}, pmid = {34143277}, issn = {1432-1459}, mesh = {Activities of Daily Living ; Brain/diagnostic imaging ; *COVID-19/complications ; Cognition ; *Cognitive Dysfunction ; Fluorodeoxyglucose F18 ; Gyrus Cinguli/diagnostic imaging ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Many patients who have suffered from acute COVID infections have long-lasting symptoms affecting several organs including the brain. This long COVID status can include "brain fog" and cognitive deficits that can disturb activities of daily living and can delay complete recovery. Here, we report two cases of neurological long COVID with abnormal FDG PET findings marked by hypometabolic regions of the cingulate cortex.}, } @article {pmid34142116, year = {2021}, author = {Guedj, E and Morbelli, S and Kaphan, E and Campion, JY and Dudouet, P and Ceccaldi, M and Cammilleri, S and Nobili, F and Eldin, C}, title = {From early limbic inflammation to long COVID sequelae.}, journal = {Brain : a journal of neurology}, volume = {144}, number = {8}, pages = {e65}, doi = {10.1093/brain/awab215}, pmid = {34142116}, issn = {1460-2156}, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; Inflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34142114, year = {2021}, author = {Meyer, PT and Blazhenets, G and Prinz, M and Hosp, JA}, title = {Reply: From early limbic inflammation to long COVID sequelae.}, journal = {Brain : a journal of neurology}, volume = {144}, number = {8}, pages = {e66}, doi = {10.1093/brain/awab216}, pmid = {34142114}, issn = {1460-2156}, mesh = {*COVID-19/complications ; Disease Progression ; Humans ; Inflammation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34140704, year = {2021}, author = {Amin-Chowdhury, Z and Ladhani, SN}, title = {Causation or confounding: why controls are critical for characterizing long COVID.}, journal = {Nature medicine}, volume = {27}, number = {7}, pages = {1129-1130}, pmid = {34140704}, issn = {1546-170X}, mesh = {COVID-19/*complications/epidemiology/etiology ; Case-Control Studies ; *Causality ; *Confounding Factors, Epidemiologic ; Humans ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34140635, year = {2022}, author = {Bornstein, SR and Voit-Bak, K and Donate, T and Rodionov, RN and Gainetdinov, RR and Tselmin, S and Kanczkowski, W and Müller, GM and Achleitner, M and Wang, J and Licinio, J and Bauer, M and Young, AH and Thuret, S and Bechmann, N and Straube, R}, title = {Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?.}, journal = {Molecular psychiatry}, volume = {27}, number = {1}, pages = {34-37}, pmid = {34140635}, issn = {1476-5578}, mesh = {*Blood Component Removal ; *COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/drug therapy ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called "post-COVID syndrome" or "long-COVID" [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.}, } @article {pmid34134757, year = {2021}, author = {Miani, C and Namer, Y}, title = {Women's voices on social media: the advent of feminist epidemiology?.}, journal = {Emerging themes in epidemiology}, volume = {18}, number = {1}, pages = {7}, pmid = {34134757}, issn = {1742-7622}, abstract = {BACKGROUND: Social media have in recent years challenged the way in which research questions are formulated in epidemiology and medicine, and in particular when it comes to women's health. They have contributed to the emergence of 'new' public health topics (e.g. gynaecological and obstetric violence, long-Covid), the unearthing of testimonials of medical injustice, and in some cases, the creation of new evidence and changes in medical practice.

MAIN TEXT: From a theoretical and methodological perspective, we observe two powerful mechanisms at play on social media, which can facilitate the implementation of feminist epidemiological research and address so-called anti-feminist bias: social media as a 'third' space and the power of groups. Social media posts can be seen as inhabiting a third space, akin to what is said off the record or in-between doors, at the end of a therapy session. Researchers somehow miss the opportunity to use the third spaces that people occupy. Similarly, another existing space that researchers are seldom interested in are peer-groups. Peer-groups are the ideal terrain to generate bottom-up research priorities. To some extent, their on-line versions provide a safe and emancipatory space, accessible, transnational, and inclusive. We would argue that this could bring feminist epidemiology to scale.

CONCLUSION: Given the emancipatory power of social media, we propose recommendations and practical implications for leveraging the potential of online-sourced feminist epidemiology at different stages of the research process (from design to dissemination), and for increasing synergies between researchers and the community. We emphasise that attention should be paid to patriarchal sociocultural contexts and power dynamics, the mitigation of risks for political recuperation and stigmatisation, and the co-production of respectful discourse on studied populations.}, } @article {pmid34129734, year = {2021}, author = {Tammaro, A and Parisella, FR and Adebanjo, GAR}, title = {Cutaneous long COVID.}, journal = {Journal of cosmetic dermatology}, volume = {20}, number = {8}, pages = {2378-2379}, pmid = {34129734}, issn = {1473-2165}, mesh = {Administration, Cutaneous ; *COVID-19/complications ; Humans ; SARS-CoV-2 ; Skin ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34128623, year = {2021}, author = {Stewart-Patterson, C and Bourgeois, R and Martin, DW}, title = {The Importance of Keeping Patients with Post-Acute Sequelae of SARS-CoV-2 Infection (Long COVID) Engaged in Work.}, journal = {American family physician}, volume = {103}, number = {12}, pages = {710}, pmid = {34128623}, issn = {1532-0650}, mesh = {COVID-19/*complications/diagnosis/epidemiology/physiopathology/psychology ; Family Practice/*methods ; Fatigue/diagnosis/etiology ; Humans ; Prognosis ; *Return to Work ; SARS-CoV-2 ; *Work Capacity Evaluation ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34127917, year = {2021}, author = {Müller, T}, title = {[Not Available].}, journal = {CME (Berlin, Germany)}, volume = {18}, number = {6}, pages = {20-21}, doi = {10.1007/s11298-021-2051-x}, pmid = {34127917}, issn = {1614-3744}, } @article {pmid34127883, year = {2021}, author = {Dollekens, B and de Louw, M}, title = {[Not Available].}, journal = {Tijdschrift voor bedrijfs- en verzekeringsgeneeskunde}, volume = {29}, number = {6-7}, pages = {10-12}, doi = {10.1007/s12498-021-1400-8}, pmid = {34127883}, issn = {1876-5858}, } @article {pmid34127310, year = {2021}, author = {Cathébras, P and Goutte, J and Gramont, B and Killian, M}, title = {["Long-haul COVID": An opportunity to address the complexity of post-infectious functional syndromes].}, journal = {La Revue de medecine interne}, volume = {42}, number = {7}, pages = {492-497}, pmid = {34127310}, issn = {1768-3122}, mesh = {COVID-19/*complications/diagnosis/epidemiology/physiopathology ; Consumer Organizations ; Diagnosis, Differential ; Humans ; Infections/*complications ; Physician-Patient Relations ; Risk Factors ; *Symptom Assessment ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, abstract = {In this work, we address the issue of prolonged symptoms following an infection by SARS-CoV-2, labeled "long COVID". This clinically unspecific syndrome must be put in perspective with the post-infectious syndromes known for a long time but ultimately poorly understood and little studied, qualified, for lack of convincing arguments for a unambiguous pathophysiology and better terms, as functional somatic syndromes. The clinical implications for clinical care ("holistic" work-up and care of patients), for research (need for truly "bio-psycho-social" investigations), and the social implications of "long COVID" (social construction of the syndrome through the experiences of patients exposed on social networks, inequalities in the face of the disease and its socioeconomic consequences) are considered. "Long COVID" must be view, because of its expected prevalence, as an opportunity to address the complexity of post-infectious (functional) syndromes, their risk factors, and the biological, psychological and social mechanisms underlying them.}, } @article {pmid34119855, year = {2021}, author = {Kappelmann, N and Dantzer, R and Khandaker, GM}, title = {Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19.}, journal = {Psychoneuroendocrinology}, volume = {131}, number = {}, pages = {105295}, pmid = {34119855}, issn = {1873-3360}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; 201486/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; R01 NS073939/NS/NINDS NIH HHS/United States ; MC_PC_17213/MRC_/Medical Research Council/United Kingdom ; MR/S037675/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anxiety/epidemiology/etiology ; COVID-19/*complications/epidemiology/etiology/psychology ; Cohort Studies ; Depression/epidemiology/etiology ; Fatigue/epidemiology/etiology ; Humans ; Interleukin-6/metabolism/pharmacology/*physiology ; Mental Disorders/epidemiology/*etiology ; Neuroimmunomodulation/drug effects/physiology ; SARS-CoV-2/physiology ; Sleep Wake Disorders/epidemiology/etiology ; Survivors/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; }, abstract = {The majority of COVID-19 survivors experience long-term neuropsychiatric symptoms such as fatigue, sleeping difficulties, depression and anxiety. We propose that neuroimmune cross-talk via inflammatory cytokines such as interleukin-6 (IL-6) could underpin these long-term COVID-19 symptoms. This hypothesis is supported by several lines of research, including population-based cohort and genetic Mendelian Randomisation studies suggesting that inflammation is associated with fatigue and sleeping difficulties, and that IL-6 could represent a possible causal driver for these symptoms. Immune activation following COVID-19 can disrupt T helper 17 (TH17) and regulatory T (Treg) cell responses, affect central learning and emotional processes, and lead to a vicious cycle of inflammation and mitochondrial dysfunction that amplifies the inflammatory process and results in immuno-metabolic constraints on neuronal energy metabolism, with fatigue being the ultimate result. Increased cytokine activity drives this process and could be targeted to interrupt it. Therefore, whether persistent IL-6 dysregulation contributes to COVID-19-related long-term fatigue, sleeping difficulties, depression, and anxiety, and whether targeting IL-6 pathways could be helpful for treatment and prevention of long COVID are important questions that require investigation. This line of research could inform new approaches for treatment and prevention of long-term neuropsychiatric symptoms of COVID-19. Effective treatment and prevention of this condition could also help to stem the anticipated rise in depression and other mental illnesses ensuing this pandemic.}, } @article {pmid34117474, year = {2021}, author = {Baker, N and Abdulla, S}, title = {Coronapod: counting the cost of long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-021-01603-w}, pmid = {34117474}, issn = {1476-4687}, } @article {pmid34115558, year = {2021}, author = {Hageman, JR}, title = {Long COVID-19 or Post-Acute Sequelae of SARS-CoV-2 Infection in Children, Adolescents, and Young Adults.}, journal = {Pediatric annals}, volume = {50}, number = {6}, pages = {e232-e233}, doi = {10.3928/19382359-20210519-02}, pmid = {34115558}, issn = {1938-2359}, } @article {pmid34111831, year = {2021}, author = {Eroğlu, İ and Eroğlu, BÇ and Güven, GS}, title = {Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19).}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {90}, number = {}, pages = {111308}, pmid = {34111831}, issn = {1873-1244}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Survivors ; Tryptophan ; Post-Acute COVID-19 Syndrome ; }, abstract = {The global pandemic of COVID-19 has been lasting for more than one year and there is little known about the long-term health effects of the disease. Long-COVID is a new term that is used to describe the enduring symptoms of COVID-19 survivors. Huang et al. reported that fatigue, muscle weakness, sleep disturbances, anxiety, and depression were the most common complaints in COVID-19 survivors after 6 months of the infection. A recent meta-analysis showed that 80% of COVID-19 survivors have developed at least one long-term symptom and the most common five were fatigue, headache, attention deficit disorder, hair loss, and dyspnea. In this paper, we discuss the hypothesis that altered tryptophan absorption and metabolism could be the main contributor to the long-term symptoms in COVID-19 survivors.}, } @article {pmid34111579, year = {2021}, author = {Peghin, M and Palese, A and Venturini, M and De Martino, M and Gerussi, V and Graziano, E and Bontempo, G and Marrella, F and Tommasini, A and Fabris, M and Curcio, F and Isola, M and Tascini, C}, title = {Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {10}, pages = {1507-1513}, pmid = {34111579}, issn = {1469-0691}, mesh = {Adolescent ; Adult ; Aged ; Antibodies, Viral/blood ; COVID-19/blood/*complications/diagnosis/epidemiology ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin G/blood ; Italy/epidemiology ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Risk Factors ; SARS-CoV-2/immunology ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To assess the prevalence of and factors associated with post-coronavirus disease 2019 (COVID-19) syndrome 6 months after the onset.

METHODS: A bidirectional prospective study. Interviews investigated symptoms potentially associated with COVID-19 6 months after the disease onset of all consecutive adult inpatients and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. IgG antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were also evaluated 6 months after the onset of symptoms, at the time of the interview.

RESULTS: A total of 599 individuals were included (320 female, 53.4%; mean age 53 years, SD 15.8) and interviewed 187 days (22 SD) after onset. The prevalence of post-COVID-19 syndrome was 40.2% (241/599). The presence of IgG antibodies was significantly associated with the occurrence of post-COVID-19 syndrome (OR 2.56, 95% CI 1.48-4.38, p 0.001) and median SARS-CoV-2 IgG titres were significantly higher in patients with post-COVID-19 syndrome than in patients without symptoms (42.1, IQR 17.1-78.4 vs. 29.1, IQR 12.1-54.2 kAU/L, p 0.004). Female gender (OR 1.55, 95% CI 1.05-2.27), a proportional increase in the number of symptoms at the onset of COVID-19 (OR 1.81, 95% CI 1.59-2.05) and ICU admission OR 3.10, 95% CI 1.18-8.11) were all independent risk factors for post-COVID-19 syndrome. The same predictors also emerged in a subgroup of 231 patients with the serological follow-up available at the time of the interview alongside the proportional increase in anti-SARS-CoV-2 IgG (OR 1.01, 95% CI 1.00-1.02, p 0.04).

DISCUSSION: Prospective follow-up could be offered to specific subgroups of COVID-10 patients, to identify typical symptoms and persistently high anti-SARS-CoV-2 IgG titres as a means of early detection of post-COVID-19 long-term sequelae.}, } @article {pmid34110078, year = {2021}, author = {Brüssow, H and Timmis, K}, title = {COVID-19: long covid and its societal consequences.}, journal = {Environmental microbiology}, volume = {23}, number = {8}, pages = {4077-4091}, doi = {10.1111/1462-2920.15634}, pmid = {34110078}, issn = {1462-2920}, mesh = {COVID-19/*complications ; Humans ; Lung ; SARS-CoV-2 ; Social Conditions ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is an acute, highly transmissible respiratory infection that is potentially lethal, but often mild, sometimes asymptomatic, especially in the young. However, it has become clear that, in some patients, there may be sequelae involving tissues other than the lung, resulting in other types of morbidity, and sometimes longer term consequences that are often termed 'long covid'. In this Lilliput, we summarize recent findings about COVID-19 sequelae, with a particular focus on long covid. We also discuss some of the long scars that COVID-19 and long covid will collectively leave on society that we term Societal Long Covid.}, } @article {pmid34109765, year = {2021}, author = {Boscolo-Rizzo, P and Guida, F and Polesel, J and Marcuzzo, AV and Capriotti, V and D'Alessandro, A and Zanelli, E and Marzolino, R and Lazzarin, C and Antonucci, P and Sacchet, E and Tofanelli, M and Borsetto, D and Gardenal, N and Pengo, M and Tirelli, G}, title = {Sequelae in adults at 12 months after mild-to-moderate coronavirus disease 2019 (COVID-19).}, journal = {International forum of allergy & rhinology}, volume = {11}, number = {12}, pages = {1685-1688}, pmid = {34109765}, issn = {2042-6984}, mesh = {Adult ; *COVID-19 ; Disease Progression ; Humans ; SARS-CoV-2 ; }, } @article {pmid34108700, year = {2021}, author = {Marshall, M}, title = {The four most urgent questions about long COVID.}, journal = {Nature}, volume = {594}, number = {7862}, pages = {168-170}, pmid = {34108700}, issn = {1476-4687}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34104285, year = {2021}, author = {Arita, Y and Yamamoto, S and Nagata, M and Ogasawara, N and Hasegawa, S}, title = {Long COVID presenting with intermittent fever after COVID-19 pneumonia.}, journal = {Radiology case reports}, volume = {16}, number = {9}, pages = {2478-2481}, pmid = {34104285}, issn = {1930-0433}, abstract = {A 72-year-old man presented to our hospital with a fever. Chest computed tomography showed typical coronavirus disease 2019 (COVID-19) pneumonia. The fever normalized after a few days, and the pneumonia was alleviated. However, the intermittent fever subsequently re-occurred and persisted for over a month. Various tests, including blood tests, culture tests, and image evaluations, were performed. However, the conclusion was that long COVID was the cause of the intermittent fever as an exclusion diagnosis. Many patients suffer from persistent symptoms of COVID-19, but the symptoms and their durations vary. Here we report a case of prolonged fever after COVID-19 pneumonia.}, } @article {pmid34103378, year = {2021}, author = {Taylor, RR and Trivedi, B and Patel, N and Singh, R and Ricketts, WM and Elliott, K and Yarwood, M and White, V and Hylton, H and Allen, R and Thomas, G and Kapil, V and McGuckin, R and Pfeffer, PE}, title = {Post-COVID symptoms reported at asynchronous virtual review and stratified follow-up after COVID-19 pneumonia.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {4}, pages = {e384-e391}, pmid = {34103378}, issn = {1473-4893}, mesh = {*COVID-19/complications ; Follow-Up Studies ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The COVID-19 pandemic has strained healthcare systems and how best to address post-COVID health needs is uncertain. Here we describe the post-COVID symptoms of 675 patients followed up using a virtual review pathway, stratified by severity of acute COVID infection.

METHODS: COVID-19 survivors completed an online/telephone questionnaire of symptoms after 12+ weeks and a chest X-ray. Dependent on findings at virtual review, patients were provided information leaflets, attended for investigations and/or were reviewed face-to-face. Outcomes were compared between patients following high-risk and low-risk admissions for COVID pneumonia, and community referrals.

RESULTS: Patients reviewed after hospitalisation for COVID pneumonia had a median of two ongoing physical health symptoms post-COVID. The most common was fatigue (50.3% of high-risk patients). Symptom burden did not vary significantly by severity of hospitalised COVID pneumonia but was highest in community referrals. Symptoms suggestive of depression, anxiety and post-traumatic stress disorder were common (depression occurred in 24.9% of high-risk patients). Asynchronous virtual review facilitated triage of patients at highest need of face-to-face review.

CONCLUSION: Many patients continue to have a significant burden of post-COVID symptoms irrespective of severity of initial pneumonia. How best to assess and manage long COVID will be of major importance over the next few years.}, } @article {pmid34103194, year = {2022}, author = {Arena, R and Myers, J and Ozemek, C and Hall, G and Severin, R and Laddu, D and Kaminsky, LA and Stoner, L and Conners, RT and Faghy, MA and , }, title = {An Evolving Approach to Assessing Cardiorespiratory Fitness, Muscle Function and Bone and Joint Health in the COVID-19 Era.}, journal = {Current problems in cardiology}, volume = {47}, number = {1}, pages = {100879}, pmid = {34103194}, issn = {1535-6280}, mesh = {Activities of Daily Living ; *COVID-19/complications ; *Cardiorespiratory Fitness ; Humans ; Muscles ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiorespiratory fitness (CRF) is now an established vital sign. CRF, along with muscle function and bone and joint health is related to functional independence and a higher quality of life. Wasserman and colleagues proposed a gear model illustrating the integrated role of the respiratory, cardiovascular, and skeletal muscle systems during aerobic exercise; in 2015, a revision to the original model was proposed. Our understanding of the effects and challenges associated with the coronavirus disease 2019 (COVID-19) are rapidly evolving. Initial evidence indicates higher levels of CRF, and muscle function protect individuals infected with COVID-19 from a complicated medical course. Moreover, for those individuals infected with COVID-19, there are initial signs of a reduction in CRF following the initial phase of recovery. We are also gaining an understanding of long COVID syndrome, where individuals who have recovered from the acute phase of viral infection present with lasting symptoms, which include but are not limited to reduced CRF, shortness of breath, and fatigue. Clearly, these individuals will require rehabilitation to restore and/or improve CRF, muscle function, bone and joint health, functional capacity (ie, the ability to perform activities of daily living), and quality of life. The importance of assessing the synergistic function of systems essential to performing activities that require physical exertion is a health care imperative. This graphical narrative provides an update to the gear model initially proposed by Wasserman and updated to a gear and circuit in 2015. External CRF, muscle function, and bone and joint health influencers and an approach to clinical assessment are also introduced.}, } @article {pmid34102037, year = {2021}, author = {Brackel, CLH and Lap, CR and Buddingh, EP and van Houten, MA and van der Sande, LJTM and Langereis, EJ and Bannier, MAGE and Pijnenburg, MWH and Hashimoto, S and Terheggen-Lagro, SWJ}, title = {Pediatric long-COVID: An overlooked phenomenon?.}, journal = {Pediatric pulmonology}, volume = {56}, number = {8}, pages = {2495-2502}, pmid = {34102037}, issn = {1099-0496}, mesh = {Adult ; *COVID-19/complications ; Child ; Dyspnea ; Fatigue/epidemiology/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children.

PATIENTS AND METHODS: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail.

RESULTS: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2-18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints.

CONCLUSION: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.}, } @article {pmid34100519, year = {2021}, author = {Wong, SW and Fan, BE and Huang, W and Chia, YW}, title = {ST-segment elevation myocardial infarction in post-COVID-19 patients: A case series.}, journal = {Annals of the Academy of Medicine, Singapore}, volume = {50}, number = {5}, pages = {425-430}, doi = {10.47102/annals-acadmedsg.202175}, pmid = {34100519}, issn = {2972-4066}, mesh = {Adult ; Blood Coagulation Tests ; *COVID-19 ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; *ST Elevation Myocardial Infarction/diagnosis/etiology ; Thrombophilia ; *Thrombosis ; }, abstract = {Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thromboembolic events in the acute setting. However, the abnormal thrombotic diathesis is not known to persist into the recovery phase of COVID-19 infection. We described 3 cases of ST-segment elevation myocardial infarction in healthy male patients who recovered from COVID-19 with no prior cardiovascular risk factors. They shared features of elevated von Willebrand factor antigen, factor VIII and D-dimer level. One patient had a borderline positive lupus anticoagulant. Intravascular ultrasound of culprit vessels revealed predominantly fibrotic plaque with minimal necrotic core. Clot waveform analysis showed parameters of hypercoagulability. They were treated with dual antiplatelet therapy, angiotensin-converting-enzyme inhibitor, beta blocker and statin. These cases highlight the strong thrombogenic nature of COVID-19 that persisted among patients who recovered from infection. Several suspected mechanisms could explain the association between vascular thrombosis in the convalescent period (endothelial dysfunction, hypercoagulability, systemic inflammatory response and vasculopathy). Additional studies on "long COVID" are essential for identifying endotheliopathy and thrombotic sequalae.}, } @article {pmid34100279, year = {2021}, author = {Theoharides, TC and Conti, P}, title = {Be aware of SARS-CoV-2 spike protein: There is more than meets the eye.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {35}, number = {3}, pages = {833-838}, doi = {10.23812/THEO_EDIT_3_21}, pmid = {34100279}, issn = {0393-974X}, mesh = {*COVID-19/complications ; Endothelial Cells ; Humans ; Pandemics ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus/genetics ; Post-Acute COVID-19 Syndrome ; }, abstract = {The COVID-19 pandemic necessitated the rapid production of vaccines aimed at the production of neutralizing antibodies against the COVID-19 spike protein required for the corona virus binding to target cells. The best well-known vaccines have utilized either mRNA or an adenovirus vector to direct human cells to produce the spike protein against which the body produces mostly neutralizing antibodies. However, recent reports have raised some skepticism as to the biologic actions of the spike protein and the types of antibodies produced. One paper reported that certain antibodies in the blood of infected patients appear to change the shape of the spike protein so as to make it more likely to bind to cells, while other papers showed that the spike protein by itself (without being part of the corona virus) can damage endothelial cells and disrupt the blood-brain barrier. These findings may be even more relevant to the pathogenesis of long-COVID syndrome that may affect as many as 50% of those infected with SARS-CoV-2. In COVID-19, a response to oxidative stress is required by increasing anti-oxidant enzymes. In this regard, it is known that polyphenols are natural anti-oxidants with multiple health effects. Hence, there are even more reasons to intervene with the use of anti-oxidant compounds, such as luteolin, in addition to available vaccines and anti-inflammatory drugs to prevent the harmful actions of the spike protein.}, } @article {pmid34097088, year = {2022}, author = {Dreßing, H and Meyer-Lindenberg, A}, title = {[Future issues in "long COVID" psychiatric assessment].}, journal = {Der Nervenarzt}, volume = {93}, number = {3}, pages = {309-312}, pmid = {34097088}, issn = {1433-0407}, mesh = {*COVID-19 ; Humans ; *Mental Disorders/diagnosis/psychology/therapy ; SARS-CoV-2 ; }, } @article {pmid34096390, year = {2021}, author = {Sarfraz, Z and Sarfraz, A and Barrios, A and Garimella, R and Dominari, A and Kc, M and Pandav, K and Pantoja, JC and Retnakumar, V and Cherrez-Ojeda, I}, title = {Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care.}, journal = {Journal of primary care & community health}, volume = {12}, number = {}, pages = {21501327211023726}, pmid = {34096390}, issn = {2150-1327}, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Humans ; Middle Aged ; Primary Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care.

METHODS: Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords "COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication." We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers.

RESULTS: We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age = 45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28 days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids.

CONCLUSION: Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.}, } @article {pmid34093286, year = {2021}, author = {Stengel, A and Malek, N and Zipfel, S and Goepel, S}, title = {Long Haulers-What Is the Evidence for Post-COVID Fatigue?.}, journal = {Frontiers in psychiatry}, volume = {12}, number = {}, pages = {677934}, pmid = {34093286}, issn = {1664-0640}, } @article {pmid34092779, year = {2021}, author = {Parums, DV}, title = {Editorial: Long COVID, or Post-COVID Syndrome, and the Global Impact on Health Care.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e933446}, pmid = {34092779}, issn = {1643-3750}, mesh = {COVID-19/*complications/economics/*epidemiology/metabolism/therapy ; Convalescence ; Delivery of Health Care ; Humans ; Pandemics ; Recovery of Function ; SARS-CoV-2/isolation & purification ; Post-Acute COVID-19 Syndrome ; }, abstract = {During 2020, increasing numbers of case reports, case series, and small observational studies reported long-term complications of coronavirus disease 2019 (COVID-19) in patients who had recovered from acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Long COVID has a prevalence of between 10-30% in patients with a recent history of SARS-CoV-2 infection. Pulmonary, hematologic, cardiovascular, neuropsychiatric, renal, endocrine, gastrointestinal and hepatobiliary, and dermatologic involvement, and chronic multisystem inflammatory syndrome in children (MIS-C) highlights the requirement for a multidisciplinary approach to the management of patients with long COVID. This Editorial aims to present the current status of long COVID, or post-COVID syndrome, and its global impact on health and the provision of health care.}, } @article {pmid34091456, year = {2021}, author = {Funke-Chambour, M and Bridevaux, PO and Clarenbach, CF and Soccal, PM and Nicod, LP and von Garnier, C and , }, title = {Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID.}, journal = {Respiration; international review of thoracic diseases}, volume = {100}, number = {8}, pages = {826-841}, pmid = {34091456}, issn = {1423-0356}, mesh = {Aftercare/*standards ; COVID-19/*complications/diagnostic imaging ; Humans ; Pulmonary Medicine/*standards ; Radiography, Thoracic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; }, abstract = {INTRODUCTION: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC).

METHOD: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of ≥70% consensus led to formulation of a recommendation.

RESULTS: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment.

CONCLUSION: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.}, } @article {pmid34090980, year = {2021}, author = {Paterson, I and Ramanathan, K and Aurora, R and Bewick, D and Chow, CM and Clarke, B and Cowan, S and Ducharme, A and Gin, K and Graham, M and Gupta, A and Jassal, DS and Kazmi, M and Krahn, A and Lamarche, Y and Marelli, A and Roifman, I and Ruel, M and Singh, G and Sterns, L and Turgeon, R and Virani, S and Wong, KK and Zieroth, S}, title = {Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team.}, journal = {The Canadian journal of cardiology}, volume = {37}, number = {8}, pages = {1260-1262}, pmid = {34090980}, issn = {1916-7075}, mesh = {COVID-19/*complications/epidemiology/physiopathology/therapy ; Canada ; *Cardiology/methods/trends ; Humans ; Hypoxia/etiology/*therapy ; Myocardial Ischemia/etiology/physiopathology/therapy ; Myocarditis/etiology/physiopathology/*therapy/virology ; *Patient Care Management/methods/organization & administration ; Patient Care Team/organization & administration ; Post-Acute COVID-19 Syndrome ; }, abstract = {It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.}, } @article {pmid34086225, year = {2021}, author = {Zimmermann, GW}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {11}, pages = {31}, doi = {10.1007/s15006-021-0073-7}, pmid = {34086225}, issn = {1613-3560}, } @article {pmid34086208, year = {2021}, author = {Facharztmagazine, R}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {11}, pages = {11}, doi = {10.1007/s15006-021-0079-1}, pmid = {34086208}, issn = {1613-3560}, } @article {pmid34084763, year = {2021}, author = {Bottino, I and Patria, MF and Milani, GP and Agostoni, C and Marchisio, P and Lelii, M and Alberzoni, M and Dell'Era, L and Castellazzi, ML and Senatore, L and Madini, B and Pensabene, MC and Rocchi, A}, title = {Can Asymptomatic or Non-Severe SARS-CoV-2 Infection Cause Medium-Term Pulmonary Sequelae in Children?.}, journal = {Frontiers in pediatrics}, volume = {9}, number = {}, pages = {621019}, pmid = {34084763}, issn = {2296-2360}, abstract = {Pulmonary complications in adults who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported even in minimally symptomatic patients. In this study, lung ultrasound (LUS) findings and pulmonary function of children who recovered from an asymptomatic or mildly symptomatic SARS-CoV-2 infection were evaluated. We prospectively followed up for at least 30 days patients younger than 18 years who recovered from SARS-CoV-2 infection at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan (Italy). All enrolled patients underwent LUS. Airway resistance measured by the interrupter technique test was assessed in subjects aged 4-6 years, whereas forced spirometry and measurement of diffusing capacity of the lungs for carbon monoxide were performed in subjects older than 6 years. To evaluate a possible correlation between pulmonary alterations and immune response to SARS-CoV-2, two semiquantitative enzyme immune assays were used. We enrolled 16 out of 23 eligible children. The median age of enrolled subjects was 7.5 (0.5-10.5) years, with a male to female ratio of 1.7. No subject presented any abnormality on LUS, airway resistance test, forced spirometry, and diffusing capacity of the lungs for carbon monoxide. On the other hand, all subjects presented Ig G against SARS-CoV-2. In contrast in adults, we did not detect any pulmonary complications in our cohort. These preliminary observations suggest that children with an asymptomatic or mildly symptomatic SARS-CoV-2 infection might be less prone to develop pulmonary complications than adults.}, } @article {pmid34082792, year = {2021}, author = {Yadav, B and Rai, A and Mundada, PS and Singhal, R and Rao, BCS and Rana, R and Srikanth, N}, title = {Safety and efficacy of Ayurvedic interventions and Yoga on long term effects of COVID-19: A structured summary of a study protocol for a randomized controlled trial.}, journal = {Trials}, volume = {22}, number = {1}, pages = {378}, doi = {10.1186/s13063-021-05326-1}, pmid = {34082792}, issn = {1745-6215}, support = {3-104/2020/CCRAS-Admn/5510//Central Council for Research in Ayurvedic Sciences, New Delhi, India/ ; }, mesh = {*COVID-19 ; Female ; Humans ; India ; Lactation ; Quality of Life ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome ; *Yoga ; }, abstract = {OBJECTIVES: Primary Objective • To assess the efficacy of Ayurveda interventions and Yoga in rehabilitation of COVID-19 cases suffering with long term effects of COVID 19 as compared to WHO Rehabilitation Self-Management after COVID-19- Related Illness. Secondary Objective • To assess the safety of Ayurvedic interventions in cases suffering with long term effects of COVID 19 TRIAL DESIGN: Multi-centric, randomized, controlled, parallel group, open-label, exploratory study. The study duration is 9 months and the intervention period is 90 days from the day of enrolment of the participant.

PARTICIPANTS: Patients of either sex between 18 to 60 years, ambulatory, willing to participate, with history (not more than 4 weeks) of positive RT-PCR for COVID-19 or IgM antibodies positivity for SARS CoV-2, but having negative RT-PCR for COVID-19 at the time of screening will be considered eligible for enrolment in the study. Critically ill patients with ARDS (acute respiratory distress syndrome), requiring invasive respiratory support in the intensive care unit, known case of any malignancy, immune-compromised state (e.g. HIV), diabetes mellitus, active pulmonary tuberculosis, past history of any chronic respiratory disease, motor neuron disease, multiple sclerosis, stroke, impaired cognition, atrial fibrillation, acute coronary syndrome, myocardial infarction, severe arrhythmia, concurrent serious hepatic disease or renal disease, pregnant or lactating women, patients on immunosuppressive medications, history of hypersensitivity to the trial drugs or their ingredients, depressive illness (before COVID-19), diagnosed psychotic illnesses, substance dependence or alcoholism will be excluded. The trial will be conducted at two medical colleges in Maharashtra, India.

INTERVENTION AND COMPARATOR: Intervention Arm (Group-I): Ayurveda interventions including Agastya Haritaki six gram and Ashwagandha tablet 500 mg twice daily orally after meals with warm water and two sessions of yoga (morning 30 minutes and evening 15 minutes) daily for 90 days, as per the post-COVID-19 care protocol provided in National Clinical Management Protocol based on Ayurveda and Yoga for management of COVID-19 published by Ministry of AYUSH, Government of India. Comparator Arm (Group-II): WHO Rehabilitation Self-Management after COVID-19 related illness for 90 days. The trial drugs are being procured from a GMP certified pharmaceutical company.

MAIN OUTCOMES: Primary Outcome: Change in respiratory function to be assessed by San Diego shortness of breath Questionnaire, 6-minutes walk test and pulmonary function test.

SECONDARY OUTCOMES: Change in High-resolution Computed Tomography (HRCT) Chest Change in Fatigue score assessed by Modified Fatigue Impact Scale Change in Anxiety score assessed by Hospital Anxiety and Depression Scale Score Change in Sleep Quality assessed by Pittsburgh Sleep Quality Index Change in the quality of life assessed by COV19-QoL scale Safety of the interventions will be assessed by comparing hematological and biochemical investigations before and after the intervention period and Adverse Event/ Adverse drug reaction TIMELINES FOR OUTCOME ASSESSMENT: Subjective parameters and clinical assessment will be assessed at baseline, 15[th] day, 30[th] day, 60[th] day and 90[th] day. Laboratory parameters (CBC, LFT, KFT, HbA1c, Hs-CRP, D-dimer), Pulmonary function test and HRCT Chest will be done at baseline and after completion of study period i.e. 90[th] day.

RANDOMISATION: Statistical package for Social Sciences (SPSS) version 15.0 is used to generate the random number sequences. The participants will be randomized to two study groups in the ratio of 1:1.

BLINDING (MASKING): The study is open-label design. However, the outcome assessor will be kept blinded regarding the study group allocation of the participants.

The sample size for the study is calculated assuming improvement in 6-minutes walk test by 40 meter in Group I and a change of 10 meter in Group II with a standard deviation of 50 meter based on the results of the previous studies, with 95% Confidence Level (α = 0.05) and 80% power and expecting a dropout rate of 20%. The number of participants to be enrolled in the study should be approximately 55 in each group. Hence, a total of 110 participants will be enrolled in the trial at each study site.

TRIAL STATUS: Participants' recruitment started on 1[st] May 2021. Anticipated end of recruitment is August 2021. Protocol number: CCRAS-01 Protocol version number: 1.1, 13th January 2021.

TRIAL REGISTRATION: The trial is prospectively registered with the Clinical Trial Registry of India (CTRI) on 03[rd] March 2021 [ CTRI/2021/03/031686 ].

FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Journal website (Additional file 1). This communication serves as a summary of the key elements of the full protocol.}, } @article {pmid34082475, year = {2021}, author = {Richter, AG and Shields, AM and Karim, A and Birch, D and Faustini, SE and Steadman, L and Ward, K and Plant, T and Reynolds, G and Veenith, T and Cunningham, AF and Drayson, MT and Wraith, DC}, title = {Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection.}, journal = {Clinical and experimental immunology}, volume = {205}, number = {2}, pages = {99-105}, pmid = {34082475}, issn = {1365-2249}, support = {MR/V028448/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_20060/MRC_/Medical Research Council/United Kingdom ; G0701275/MRC_/Medical Research Council/United Kingdom ; BB/L009986/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/N023706/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Aged ; *Antibody Specificity ; *Autoantibodies/blood/immunology ; *COVID-19/blood/immunology ; Female ; Humans ; Male ; Middle Aged ; Organ Specificity ; *SARS-CoV-2/immunology/metabolism ; Severity of Illness Index ; }, abstract = {Coronavirus 19 (COVID-19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS-CoV-2, suffering from COVID-19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non-COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID-19 ITU group compared with non-COVID-19 ITU disease control patients and that autoantibodies were also found in the serum 3-5 months post-COVID-19 infection. Non-COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID-19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS-CoV-2 is associated with the detection of a limited profile of tissue-specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS-CoV-2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies.}, } @article {pmid34078004, year = {2021}, author = {Pujari, S and Gaikwad, S and Chitalikar, A and Dabhade, D and Joshi, K and Bele, V}, title = {Long-coronavirus disease among people living with HIV in western India: An observational study.}, journal = {Immunity, inflammation and disease}, volume = {9}, number = {3}, pages = {1037-1043}, pmid = {34078004}, issn = {2050-4527}, mesh = {COVID-19/*complications/epidemiology ; Female ; *HIV Infections/epidemiology ; Humans ; India/epidemiology ; Male ; Middle Aged ; Prospective Studies ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Long-COVID is emerging as a significant problem among individuals who recovered from COVID-19. Scant information is available on the prevalence, characteristics, and risk factors for long-COVID among people living with HIV (PLHIV).

SETTING: A tertiary level, private, HIV clinic in western India.

METHODS: A prospective, observational study was conducted to assess the prevalence of long-COVID among PLHIV. Long-COVID was defined as the presence of at least one symptom after 30 days of illness onset. A questionnaire for assessing general, cardiorespiratory, neuro-psychiatric, and gastro-intestinal symptoms was used to screen individuals with history of confirmed COVID-19. Data on demographics, HIV-related variables, comorbidities, and severity of COVID-19 were abstracted from electronic medical records. Univariate and multivariate logistic regression were used to identify risk factors for long-COVID.

RESULTS: Ninety-four PLHIV were screened for long-COVID. Median (interquartile range [IQR]) age was 51 (47-56) years and 73.4% were males. The majority (76.6%) had a history of asymptomatic-mild COVID-19 illness. The prevalence of long-COVID was 43.6% (95% confidence interval [CI], 33.4-54.2). Moderate-severe COVID-19 illness was significantly associated with long-COVID (adjusted odds ratio, 4.7; 95% CI, 1.4-17.9; p = .016). Among individuals with long-COVID, cough (22.3%) and fatigue (19.1%) were the commonest symptoms. The median (IQR) duration for resolution of symptoms was 15 (7-30) days. Ten individuals (10.6%) had persistent symptoms at a median of 109 days since the onset of COVID-19.

CONCLUSION: Long-COVID is common among PLHIV with moderate-severe acute COVID-19 illness. There is a need for integration of long-COVID diagnosis and care services within antiretroviral therapy clinics for PLHIV with COVID-19.}, } @article {pmid34076561, year = {2021}, author = {Gandotra, S and Russell, D}, title = {The Long and the Short of It: Is "Long COVID" More Than Slow Resolution of the Acute Disease?.}, journal = {Annals of the American Thoracic Society}, volume = {18}, number = {6}, pages = {948-950}, pmid = {34076561}, issn = {2325-6621}, support = {K08 HL148514/HL/NHLBI NIH HHS/United States ; }, mesh = {Acute Disease ; *COVID-19 ; Humans ; SARS-CoV-2 ; }, } @article {pmid34072390, year = {2021}, author = {Desimmie, BA and Raru, YY and Awadh, HM and He, P and Teka, S and Willenburg, KS}, title = {Insights into SARS-CoV-2 Persistence and Its Relevance.}, journal = {Viruses}, volume = {13}, number = {6}, pages = {}, pmid = {34072390}, issn = {1999-4915}, mesh = {COVID-19/immunology/physiopathology/prevention & control/*virology ; Humans ; Reinfection ; SARS-CoV-2/immunology/*physiology ; Viral Tropism ; Virus Shedding ; }, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), continues to wreak havoc, threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, accurately identifying acute infections, and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here, we present a living literature review (January 2020 through 15 March 2021) on SARS-CoV-2 viral persistence, reinfection, and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.}, } @article {pmid34071264, year = {2021}, author = {Muirhead, N and Muirhead, J and Lavery, G and Marsh, B}, title = {Medical School Education on Myalgic Encephalomyelitis.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {6}, pages = {}, pmid = {34071264}, issn = {1648-9144}, mesh = {*COVID-19 ; *Education, Medical ; *Fatigue Syndrome, Chronic/diagnosis/therapy ; Humans ; Quality of Life ; SARS-CoV-2 ; Schools, Medical ; }, abstract = {Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades, the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. Meanwhile, there has been an exponential increase in biomedical research and an international paradigm shift in the literature, which defines ME/CFS as a multisystem disease, replacing the psychogenic narrative. This study was designed to explore the current UK medical school education on ME/CFS and to identify challenges and opportunities relating to future ME/CFS medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK medical schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%); of these 13/22 (59%) taught ME/CFS, and teaching was led by lecturers from ten medical specialties. Teaching delivery was usually by lecture; discussion, case studies and e-learning were also used. Questions on ME/CFS were included by seven schools in their examinations and three schools reported likely clinical exposure to ME/CFS patients. Two-thirds of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus, so it was not possible to ascertain what the students were being taught. Conclusions: This exploratory study reveals inadequacies in medical school teaching on ME/CFS. Many medical schools (64% of respondents) acknowledge the need to update ME/CFS education by expressing an appetite for further educational materials. The General Medical Council (GMC) and Medical Schools Council (MSC) are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC is urged to consider creating a registered specialty encompassing ME/CFS, post-viral fatigue and long Covid.}, } @article {pmid34068009, year = {2021}, author = {Orrù, G and Bertelloni, D and Diolaiuti, F and Mucci, F and Di Giuseppe, M and Biella, M and Gemignani, A and Ciacchini, R and Conversano, C}, title = {Long-COVID Syndrome? A Study on the Persistence of Neurological, Psychological and Physiological Symptoms.}, journal = {Healthcare (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {34068009}, issn = {2227-9032}, abstract = {BACKGROUND: Emerging aspects of the Covid-19 clinical presentation are its long-term effects, which are characteristic of the so-called "long COVID". The aim of the present study was to investigate the prevalence of physical, psychological, and sleep disturbances and the quality of life in the general population during the ongoing pandemic.

METHODS: This study, based on an online survey, collected demographic data, information related to COVID-19, sleep disturbances, and quality of life data from 507 individuals. The level of sleep disturbances and quality of life was assessed through the Insomnia Severity Index (ISI) and the EuroQol-5D (EQ-5D), respectively.

RESULTS: In total, 507 individuals (M = 91 and F = 416 women) completed the online survey. The main symptoms associated with "long COVID" were headache, fatigue, muscle aches/myalgia, articular pains, cognitive impairment, loss of concentration, and loss of smell. Additionally, the subjects showed significant levels of insomnia (p < 0.05) and an overall reduced quality of life (p < 0.05).

CONCLUSIONS: The results of the study appear in line with recent publications, but uncertainty regarding the definition and specific features of "long COVID" remains. Further studies are needed in order to better define the clinical presentation of the "long COVID" condition and related targeted treatments.}, } @article {pmid34067776, year = {2021}, author = {Jimeno-Almazán, A and Pallarés, JG and Buendía-Romero, Á and Martínez-Cava, A and Franco-López, F and Sánchez-Alcaraz Martínez, BJ and Bernal-Morel, E and Courel-Ibáñez, J}, title = {Post-COVID-19 Syndrome and the Potential Benefits of Exercise.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34067776}, issn = {1660-4601}, mesh = {*COVID-19 ; Exercise ; Humans ; Pandemics ; *SARS-CoV-2 ; }, abstract = {The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.}, } @article {pmid34066174, year = {2021}, author = {Chakraborty, T and Jamal, RF and Battineni, G and Teja, KV and Marto, CM and Spagnuolo, G}, title = {A Review of Prolonged Post-COVID-19 Symptoms and Their Implications on Dental Management.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {10}, pages = {}, pmid = {34066174}, issn = {1660-4601}, mesh = {*COVID-19 ; Cohort Studies ; Cross-Sectional Studies ; Dental Care ; Humans ; SARS-CoV-2 ; }, abstract = {The available data regarding the short and long-term consequences of COVID-19 is still insufficient. This narrative review aims to provide information on the prolonged COVID-19 symptoms in recovered patients and their implications during dental management. Additionally, this manuscript highlights the oral manifestations of COVID-19 and its management. A systematic search was conducted in PubMed, Embase, Cochrane Library and Web of Science databases, WHO and CDC websites, and grey literature was searched through Google Scholar. Clinical articles (clinical trials, case-reports, cohort, and cross-sectional studies) were included, reporting prolonged post-COVID-19 symptoms. Although COVID-19 is an infectious disease primarily affecting the lungs, its multi-organ involvement is responsible for several prolonged symptoms, including oral implications. In recovered patients with prolonged COVID-19 symptoms, considerations for providing dental treatment has to be made as they can present with assortment of symptoms. These prolonged post-COVID-19 symptoms can affect the delivery of the required dental treatment. Hence, the recommendations proposed in this narrative review can be a useful starting point to aid dental teams providing adequate care for such recovered patients.}, } @article {pmid34062184, year = {2021}, author = {Raw, RK and Kelly, CA and Rees, J and Wroe, C and Chadwick, DR}, title = {Previous COVID-19 infection, but not Long-COVID, is associated with increased adverse events following BNT162b2/Pfizer vaccination.}, journal = {The Journal of infection}, volume = {83}, number = {3}, pages = {381-412}, pmid = {34062184}, issn = {1532-2742}, mesh = {BNT162 Vaccine ; *COVID-19 ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Vaccination ; }, } @article {pmid34060675, year = {2022}, author = {Buonsenso, D and Fusco, C and De Rose, C and Valentini, P and Vergari, J}, title = {Long COVID in children: Partnerships between families and paediatricians are a priority for better care.}, journal = {Journal of paediatrics and child health}, volume = {58}, number = {1}, pages = {201-202}, pmid = {34060675}, issn = {1440-1754}, mesh = {*COVID-19/complications ; Child ; Humans ; Pediatricians ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34059034, year = {2021}, author = {Westerlind, E and Palstam, A and Sunnerhagen, KS and Persson, HC}, title = {Patterns and predictors of sick leave after Covid-19 and long Covid in a national Swedish cohort.}, journal = {BMC public health}, volume = {21}, number = {1}, pages = {1023}, pmid = {34059034}, issn = {1471-2458}, mesh = {Aged ; *COVID-19 ; Cohort Studies ; Humans ; SARS-CoV-2 ; *Sick Leave ; Sweden/epidemiology ; }, abstract = {BACKGROUND: The impact of Covid-19 and its long-term consequences is not yet fully understood. Sick leave can be seen as an indicator of health in a working age population, and the present study aimed to investigate sick-leave patterns after Covid-19, and potential factors predicting longer sick leave in hospitalised and non-hospitalised people with Covid-19.

METHODS: The present study is a comprehensive national registry-based study in Sweden with a 4-month follow-up. All people who started to receive sickness benefits for Covid-19 during March 1 to August 31, 2020, were included. Predictors of sick leave ≥1 month and long Covid (≥12 weeks) were analysed with logistic regression in the total population and in separate models depending on inpatient care due to Covid-19.

RESULTS: A total of 11,955 people started sick leave for Covid-19 within the inclusion period. The median sick leave was 35 days, 13.3% were on sick leave for long Covid, and 9.0% remained on sick leave for the whole follow-up period. There were 2960 people who received inpatient care due to Covid-19, which was the strongest predictor of longer sick leave. Sick leave the year prior to Covid-19 and older age also predicted longer sick leave. No clear pattern of socioeconomic factors was noted.

CONCLUSIONS: A substantial number of people are on sick leave due to Covid-19. Sick leave may be protracted, and sick leave for long Covid is quite common. The severity of Covid-19 (needing inpatient care), prior sick leave, and age all seem to predict the likelihood of longer sick leave. However, no socioeconomic factor could clearly predict longer sick leave, indicating the complexity of this condition. The group needing long sick leave after Covid-19 seems to be heterogeneous, indicating a knowledge gap.}, } @article {pmid34050501, year = {2021}, author = {Roe, K}, title = {The Symptoms and Clinical Manifestations Observed in COVID-19 Patients/Long COVID-19 Symptoms that Parallel Toxoplasma gondii Infections.}, journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology}, volume = {16}, number = {3}, pages = {513-516}, pmid = {34050501}, issn = {1557-1904}, mesh = {Brain/parasitology/pathology ; COVID-19/*complications/diagnosis/etiology/mortality/physiopathology ; Humans ; Toxoplasma/isolation & purification ; Toxoplasmosis/*diagnosis/*mortality/physiopathology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34045738, year = {2021}, author = {Sudre, CH and Murray, B and Varsavsky, T and Graham, MS and Penfold, RS and Bowyer, RC and Pujol, JC and Klaser, K and Antonelli, M and Canas, LS and Molteni, E and Modat, M and Jorge Cardoso, M and May, A and Ganesh, S and Davies, R and Nguyen, LH and Drew, DA and Astley, CM and Joshi, AD and Merino, J and Tsereteli, N and Fall, T and Gomez, MF and Duncan, EL and Menni, C and Williams, FMK and Franks, PW and Chan, AT and Wolf, J and Ourselin, S and Spector, T and Steves, CJ}, title = {Author Correction: Attributes and predictors of long COVID.}, journal = {Nature medicine}, volume = {27}, number = {6}, pages = {1116}, doi = {10.1038/s41591-021-01361-2}, pmid = {34045738}, issn = {1546-170X}, } @article {pmid34045207, year = {2022}, author = {Munblit, D and Simpson, F and Mabbitt, J and Dunn-Galvin, A and Semple, C and Warner, JO}, title = {Legacy of COVID-19 infection in children: long-COVID will have a lifelong health/economic impact.}, journal = {Archives of disease in childhood}, volume = {107}, number = {3}, pages = {e2}, doi = {10.1136/archdischild-2021-321882}, pmid = {34045207}, issn = {1468-2044}, mesh = {COVID-19/*complications/economics/psychology ; Child ; Education, Distance ; Humans ; Pandemics ; Parents/psychology ; Quarantine/psychology ; SARS-CoV-2 ; Social Isolation/psychology ; Unemployment ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34041295, year = {2021}, author = {Vaes, AW and Goërtz, YMJ and Van Herck, M and Machado, FVC and Meys, R and Delbressine, JM and Houben-Wilke, S and Gaffron, S and Maier, D and Burtin, C and Posthuma, R and van Loon, NPH and Franssen, FME and Hajian, B and Simons, SO and van Boven, JFM and Klok, FA and Spaetgens, B and Pinxt, CMH and Liu, LYL and Wesseling, G and Spies, Y and Vijlbrief, H and van 't Hul, AJ and Janssen, DJA and Spruit, MA}, title = {Recovery from COVID-19: a sprint or marathon? 6-month follow-up data from online long COVID-19 support group members.}, journal = {ERJ open research}, volume = {7}, number = {2}, pages = {}, pmid = {34041295}, issn = {2312-0541}, abstract = {BACKGROUND: It remains unknown whether and to what extent members of online "long COVID" peer support groups remain symptomatic and limited over time. Therefore, we aimed to evaluate symptoms in members of online long COVID peer support groups up to 6 months after the onset of coronavirus disease 2019 (COVID-19)-related symptoms.

METHODS: Demographics, symptoms, health status, work productivity, functional status and health-related quality of life were assessed about 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID peer support groups.

RESULTS: Data from 239 patients with a confirmed COVID-19 diagnosis (83% women; median (interquartile range) age 50 (39-56) years) were analysed. During the infection, a median (interquartile range) of 15 (11-18) symptoms was reported, which was significantly lower 3 and 6 months later: 6 (4-9) and 6 (3-8), respectively (p<0.05). From 3 to 6 months follow-up, the proportion of patients without symptoms increased from 1.3% to only 5.4% (p<0.001). Patients also reported a significantly improved work productivity (work absenteeism and presenteeism: 73% versus 52% and 66% versus 60%, respectively), self-reported good health (9.2% versus 16.7%), functional status (mean±sd Post-COVID-19 Functional Status scale: 2.4±0.9 versus 2.2±1.0) and health-related quality of life (all p<0.05).

CONCLUSION: Although patients with confirmed COVID-19, who were all members of online long COVID peer support groups, reported significant improvements in work productivity, functional status and quality of life between 3 and 6 months follow-up, these data clearly highlight the long-term impact of COVID-19, as approximately 6 months after the onset of COVID-19-related symptoms a large proportion still experienced persistent symptoms, a moderate-to-poor health, moderate-to-severe functional limitations, considerable loss in work productivity, and/or an impaired quality of life. Action is needed to improve the management and healthcare of these patients.}, } @article {pmid34039662, year = {2021}, author = {Twycross, A}, title = {Living with long Covid: some reflections 14 months down the line.}, journal = {Evidence-based nursing}, volume = {}, number = {}, pages = {}, doi = {10.1136/ebnurs-2021-103449}, pmid = {34039662}, issn = {1468-9618}, } @article {pmid34036253, year = {2021}, author = {Iqbal, FM and Lam, K and Sounderajah, V and Clarke, JM and Ashrafian, H and Darzi, A}, title = {Characteristics and predictors of acute and chronic post-COVID syndrome: A systematic review and meta-analysis.}, journal = {EClinicalMedicine}, volume = {36}, number = {}, pages = {100899}, pmid = {34036253}, issn = {2589-5370}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_18032/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: A significant proportion of individuals experience lingering and debilitating symptoms following acute COVID-19 infection. The National Institute for Health and Care Excellence (NICE) have coined the persistent cluster of symptoms as post-COVID syndrome. This has been further sub-categorised into acute post-COVID syndrome for symptoms persisting three weeks beyond initial infection and chronic post-COVID syndrome for symptoms persisting beyond twelve weeks. The aim of this review was to detail the prevalence of clinical features and identify potential predictors for acute and chronic post-COVID syndrome.

METHODS: A systematic literature search, with no language restrictions, was performed to identify studies detailing characteristics and outcomes related to survivorship of post-COVID syndrome. The last search was performed on 6 March 2021 and all pre-dating published articles included. A means of proportion meta-analysis was performed to quantify characteristics of acute and chronic post-COVID syndrome. Study quality was assessed with a specific risk of bias tool. PROSPERO Registration: CRD42020222855.

FINDINGS: A total of 43 studies met the eligibility criteria; of which, 38 allowed for meta-analysis. Fatigue and dyspnoea were the most prevalent symptoms in acute post-COVID (0·37 and 0·35) and fatigue and sleep disturbance in chronic post-COVID syndrome (0·48 and 0·44), respectively. The available evidence is generally of poor quality, with considerable risk of bias, and are of observational design.

INTERPRETATION: In conclusion, this review highlights that flaws in data capture and interpretation, noted in the uncertainty within our meta-analysis, affect the applicability of current knowledge. Policy makers and researchers must focus on understanding the impact of this condition on individuals and society with appropriate funding initiatives and global collaborative research.}, } @article {pmid34036244, year = {2021}, author = {Martelletti, P and Bentivegna, E and Spuntarelli, V and Luciani, M}, title = {Long-COVID Headache.}, journal = {SN comprehensive clinical medicine}, volume = {3}, number = {8}, pages = {1704-1706}, pmid = {34036244}, issn = {2523-8973}, abstract = {The so-called long COVID-19 is a set of symptoms that accompanies the patient even for months after discharge from the hospital. These symptoms include easy muscle fatigue, moderate breathlessness, persistent headache, the feeling of a foggy head, and the development of psychiatric disorders. In general, the quality of life of at least half of the patients who come out of the COVID-19 syndrome, both mild and severe, shows a markedly worsening despite having passed a difficult physical and psychological test. Among all the neurological disorders that can most frequently be found in the long COVID-19, it is important to consider the persistent headache symptomatology as a possible chronic sequela of the infection. Since there is not a definition in the International Headache Society classification of this type of headache, we must focus our attention on this long-COVID-19 headache especially because clinical studies are being planned to collect big data for the International Headache Society Classification Committee.}, } @article {pmid34035919, year = {2021}, author = {Omololu, A and Ojelade, B and Ajayi, O and Adesomi, T and Alade, O and Adebisi, S and Nwadike, V}, title = {"Long COVID": A case report of persistent symptoms in a patient with prolonged SARS-CoV-2 shedding for over 110 days.}, journal = {SAGE open medical case reports}, volume = {9}, number = {}, pages = {2050313X211015494}, pmid = {34035919}, issn = {2050-313X}, abstract = {Coronavirus disease 2019 is a novel disease currently ravaging the world as a pandemic. More emphasis has been focused on the acute disease, with less attention on the detection and management of long-term sequelae which develop in some patients, variously termed "Long COVID," Post-coronavirus disease 2019 syndrome, or ongoing coronavirus disease. There are also various reports in the literature on the duration of viral shedding, with the longest known recorded being about 70 days, and whether this duration has an effect on prognosis or patients remaining infectious is still unknown. We report the case of a 22-year-old health care worker with prolonged multi-systemic features of coronavirus disease 2019 including cardiovascular, respiratory, central nervous system, and musculoskeletal symptoms lasting about 18 weeks from symptom onset, though never hospitalized, and persistent detection of severe acute respiratory syndrome coronavirus 2 attributed to viral shedding for over 110 days, which is the longest duration recorded to our knowledge.}, } @article {pmid34035524, year = {2021}, author = {Montefusco, L and Ben Nasr, M and D'Addio, F and Loretelli, C and Rossi, A and Pastore, I and Daniele, G and Abdelsalam, A and Maestroni, A and Dell'Acqua, M and Ippolito, E and Assi, E and Usuelli, V and Seelam, AJ and Fiorina, RM and Chebat, E and Morpurgo, P and Lunati, ME and Bolla, AM and Finzi, G and Abdi, R and Bonventre, JV and Rusconi, S and Riva, A and Corradi, D and Santus, P and Nebuloni, M and Folli, F and Zuccotti, GV and Galli, M and Fiorina, P}, title = {Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection.}, journal = {Nature metabolism}, volume = {3}, number = {6}, pages = {774-785}, pmid = {34035524}, issn = {2522-5812}, support = {K24 AI116925/AI/NIAID NIH HHS/United States ; R37 DK039773/DK/NIDDK NIH HHS/United States ; }, mesh = {Blood Glucose/*metabolism ; COVID-19/*blood/complications/virology ; Cohort Studies ; Humans ; Hyperglycemia/complications/*metabolism ; Insulin Resistance ; Insulin-Secreting Cells/pathology ; SARS-CoV-2/isolation & purification ; }, abstract = {Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.}, } @article {pmid34030861, year = {2021}, author = {Ausín-García, C and Cervilla-Muñoz, E and Millán-Nuñez-Cortés, J}, title = {Long-term consequences of SARS-COV2 infection: Long-Covid patterns and possible public health implications.}, journal = {Medicina clinica}, volume = {157}, number = {7}, pages = {e293-e294}, pmid = {34030861}, issn = {1578-8989}, mesh = {*COVID-19/complications/epidemiology ; Humans ; *Public Health ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34027514, year = {2021}, author = {Augustin, M and Schommers, P and Stecher, M and Dewald, F and Gieselmann, L and Gruell, H and Horn, C and Vanshylla, K and Cristanziano, VD and Osebold, L and Roventa, M and Riaz, T and Tschernoster, N and Altmueller, J and Rose, L and Salomon, S and Priesner, V and Luers, JC and Albus, C and Rosenkranz, S and Gathof, B and Fätkenheuer, G and Hallek, M and Klein, F and Suárez, I and Lehmann, C}, title = {Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study.}, journal = {The Lancet regional health. Europe}, volume = {6}, number = {}, pages = {100122}, pmid = {34027514}, issn = {2666-7762}, abstract = {BACKGROUND: While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients.

METHODS: 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model.

FINDINGS: We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms.

INTERPRETATION: The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19.

FUNDING: COVIM:"NaFoUniMedCovid19"(FKZ: 01KX2021).}, } @article {pmid34025675, year = {2021}, author = {Townsend, L and Dyer, AH and Naughton, A and Kiersey, R and Holden, D and Gardiner, M and Dowds, J and O'Brien, K and Bannan, C and Nadarajan, P and Dunne, J and Martin-Loeches, I and Fallon, PG and Bergin, C and O'Farrelly, C and Cheallaigh, CN and Bourke, NM and Conlon, N}, title = {Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {676932}, pmid = {34025675}, issn = {1664-3224}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Age Factors ; Aged ; Aging/*physiology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; COVID-19/*immunology ; Cohort Studies ; Convalescence ; Female ; Humans ; Immunophenotyping ; Longitudinal Studies ; Lymphocyte Activation ; Male ; Middle Aged ; Pandemics ; SARS-CoV-2/*physiology ; }, abstract = {OBJECTIVES: The immunological and inflammatory changes following acute COVID-19 are hugely variable. Persistent clinical symptoms following resolution of initial infection, termed long COVID, are also hugely variable, but association with immunological changes has not been described. We investigate changing immunological parameters in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms.

METHODS: We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed as cardinal features of long COVID using the Chalder Fatigue Scale and 6-minute-walk test. The relationships between these clinical outcomes and convalescent immunological results were investigated.

RESULTS: We identify persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common in this cohort. These symptoms were not associated with immune cell populations or circulating inflammatory cytokines.

CONCLUSION: We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.}, } @article {pmid34024217, year = {2021}, author = {Yong, SJ}, title = {Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.}, journal = {Infectious diseases (London, England)}, volume = {53}, number = {10}, pages = {737-754}, pmid = {34024217}, issn = {2374-4243}, mesh = {*COVID-19/complications ; Female ; Humans ; *Mental Disorders ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.}, } @article {pmid34019446, year = {2021}, author = {Funke-Chambour, M and Feldmeyer, L and Hoepner, R and Huynh-Do, U and Maurer, B and Rexhaj, E and Geiser, T}, title = {[The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection].}, journal = {Praxis}, volume = {110}, number = {7}, pages = {377-382}, doi = {10.1024/1661-8157/a003678}, pmid = {34019446}, issn = {1661-8157}, mesh = {*COVID-19 ; Humans ; Lung ; SARS-CoV-2 ; Syndrome ; }, abstract = {The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection Abstract. Long-term consequences are increasingly reported in the current literature after COVID-19 infections. Some patients suffer from persistent pulmonary and extrapulmonary symptoms even months after the acute infection. Pulmonary impairment, but also dysregulation and effects on immune system, cardiovascular system, neurological system, skin and kidney are described or anticipated. This mini review gives a short update to the practitioner about the current knowledge about Long COVID.}, } @article {pmid34016942, year = {2021}, author = {Stefano, GB and Büttiker, P and Weissenberger, S and Martin, A and Ptacek, R and Kream, RM}, title = {Editorial: The Pathogenesis of Long-Term Neuropsychiatric COVID-19 and the Role of Microglia, Mitochondria, and Persistent Neuroinflammation: A Hypothesis.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e933015}, pmid = {34016942}, issn = {1643-3750}, mesh = {COVID-19/*complications/pathology ; Central Nervous System/*pathology ; Cognitive Dysfunction/*etiology/pathology ; Humans ; Inflammation/*pathology ; Microglia/*pathology ; Mitochondria/*pathology ; Neurons/pathology ; SARS-CoV-2 ; }, abstract = {Persistent comorbidities occur in patients who initially recover from acute coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 'Long COVID' involves the central nervous system (CNS), resulting in neuropsychiatric symptoms and signs, including cognitive impairment or 'brain fog' and chronic fatigue syndrome. There are similarities in these persistent complications between SARS-CoV-2 and the Ebola, Zika, and influenza A viruses. Normal CNS neuronal mitochondrial function requires high oxygen levels for oxidative phosphorylation and ATP production. Recent studies have shown that the SARS-CoV-2 virus can hijack mitochondrial function. Persistent changes in cognitive functioning have also been reported with other viral infections. SARS-CoV-2 infection may result in long-term effects on immune processes within the CNS by causing microglial dysfunction. This short opinion aims to discuss the hypothesis that the pathogenesis of long-term neuropsychiatric COVID-19 involves microglia, mitochondria, and persistent neuroinflammation.}, } @article {pmid34016708, year = {2021}, author = {Lever, J and Altman, RB}, title = {Analyzing the vast coronavirus literature with CoronaCentral.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {23}, pages = {}, pmid = {34016708}, issn = {1091-6490}, support = {LM05652/NH/NIH HHS/United States ; }, mesh = {Animals ; *COVID-19/epidemiology/metabolism/therapy/transmission ; Humans ; *Machine Learning ; Middle East Respiratory Syndrome Coronavirus/*metabolism/pathogenicity ; *Pandemics ; SARS-CoV-2/*metabolism/pathogenicity ; *Severe Acute Respiratory Syndrome/epidemiology/metabolism/therapy/transmission ; }, abstract = {The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as "long COVID" and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.}, } @article {pmid34015528, year = {2021}, author = {Guedj, E and Lazarini, F and Morbelli, S and Ceccaldi, M and Hautefort, C and Kas, A and Radulesco, T and Salmon-Ceron, D and Eldin, C}, title = {Long COVID and the brain network of Proust's madeleine: targeting the olfactory pathway.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {9}, pages = {1196-1198}, pmid = {34015528}, issn = {1469-0691}, mesh = {COVID-19/*complications/diagnostic imaging/metabolism ; Fluorodeoxyglucose F18 ; Humans ; Memory Disorders/virology ; Olfaction Disorders/*diagnostic imaging/*virology ; Olfactory Bulb/*diagnostic imaging/metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid34011495, year = {2021}, author = {Mayor, N and Tsang, R and Joy, M and Hobbs, FR and de Lusignan, S}, title = {Long covid: coding is caring.}, journal = {BMJ (Clinical research ed.)}, volume = {373}, number = {}, pages = {n1262}, doi = {10.1136/bmj.n1262}, pmid = {34011495}, issn = {1756-1833}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, } @article {pmid34011359, year = {2021}, author = {Romero-Duarte, Á and Rivera-Izquierdo, M and Guerrero-Fernández de Alba, I and Pérez-Contreras, M and Fernández-Martínez, NF and Ruiz-Montero, R and Serrano-Ortiz, Á and González-Serna, RO and Salcedo-Leal, I and Jiménez-Mejías, E and Cárdenas-Cruz, A}, title = {Sequelae, persistent symptomatology and outcomes after COVID-19 hospitalization: the ANCOHVID multicentre 6-month follow-up study.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {129}, pmid = {34011359}, issn = {1741-7015}, mesh = {Adult ; Aftercare ; Aged ; Aged, 80 and over ; COVID-19/*complications ; Cohort Studies ; Disease Progression ; Female ; Follow-Up Studies ; Hospitalization ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Pandemics ; Patient Discharge ; Patient Readmission ; Retrospective Studies ; SARS-CoV-2 ; Spain ; Young Adult ; }, abstract = {BACKGROUND: Long-term effects of COVID-19, also called Long COVID, affect more than 10% of patients. The most severe cases (i.e. those requiring hospitalization) present a higher frequency of sequelae, but detailed information on these effects is still lacking. The objective of this study is to identify and quantify the frequency and outcomes associated with the presence of sequelae or persistent symptomatology (SPS) during the 6 months after discharge for COVID-19.

METHODS: Retrospective observational 6-month follow-up study conducted in four hospitals of Spain. A cohort of all 969 patients who were hospitalized with PCR-confirmed SARS-CoV-2 from March 1 to April 15, 2020, was included. We collected all the SPS during the 6 months after discharge reported by patients during follow-up from primary care records. Cluster analyses were performed to validate the measures. The main outcome measures were return to the Emergency Services, hospital readmission and post-discharge death. Surviving patients' outcomes were collected through clinical histories and primary care reports. Multiple logistic regression models were applied.

RESULTS: The 797 (82.2%) patients who survived constituted the sample followed, while the rest died from COVID-19. The mean age was 63.0 years, 53.7% of them were men and 509 (63.9%) reported some sequelae during the first 6 months after discharge. These sequelae were very diverse, but the most frequent were respiratory (42.0%), systemic (36.1%), neurological (20.8%), mental health (12.2%) and infectious (7.9%) SPS, with some differences by sex. Women presented higher frequencies of headache and mental health SPS, among others. A total of 160 (20.1%) patients returned to the Emergency Services, 35 (4.4%) required hospital readmission and 8 (1.0%) died during follow-up. The main factors independently associated with the return to Emergency Services were persistent fever, dermatological SPS, arrythmia or palpitations, thoracic pain and pneumonia.

CONCLUSIONS: COVID-19 cases requiring hospitalization during the first wave of the pandemic developed a significant range of mid- to long-term SPS. A detailed list of symptoms and outcomes is provided in this multicentre study. Identification of possible factors associated with these SPS could be useful to optimize preventive follow-up strategies in primary care for the coming months of the pandemic.}, } @article {pmid34009992, year = {2021}, author = {Holmes, E and Wist, J and Masuda, R and Lodge, S and Nitschke, P and Kimhofer, T and Loo, RL and Begum, S and Boughton, B and Yang, R and Morillon, AC and Chin, ST and Hall, D and Ryan, M and Bong, SH and Gay, M and Edgar, DW and Lindon, JC and Richards, T and Yeap, BB and Pettersson, S and Spraul, M and Schaefer, H and Lawler, NG and Gray, N and Whiley, L and Nicholson, JK}, title = {Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome.}, journal = {Journal of proteome research}, volume = {20}, number = {6}, pages = {3315-3329}, doi = {10.1021/acs.jproteome.1c00224}, pmid = {34009992}, issn = {1535-3907}, mesh = {*COVID-19/complications ; Humans ; Lipoproteins ; Magnetic Resonance Spectroscopy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of "Post-Acute COVID-19 Syndrome", colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10[-3] versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10[-8] versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10[-3]) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ[2]p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.}, } @article {pmid34006526, year = {2021}, author = {Berry, P}, title = {Use patient reported outcome measures (PROMs) in treatment of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {373}, number = {}, pages = {n1260}, doi = {10.1136/bmj.n1260}, pmid = {34006526}, issn = {1756-1833}, mesh = {*COVID-19 ; Humans ; Patient Reported Outcome Measures ; SARS-CoV-2 ; Surveys and Questionnaires ; }, } @article {pmid34003294, year = {2021}, author = {Godeau, D and Petit, A and Richard, I and Roquelaure, Y and Descatha, A}, title = {Return-to-work, disabilities and occupational health in the age of COVID-19.}, journal = {Scandinavian journal of work, environment & health}, volume = {47}, number = {5}, pages = {408-409}, pmid = {34003294}, issn = {1795-990X}, mesh = {*COVID-19/complications ; Cohort Studies ; Communicable Disease Control ; *Disabled Persons ; France/epidemiology ; Humans ; Male ; *Occupational Health ; Pandemics ; Reproducibility of Results ; Return to Work ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {We have read with great interest the two editorials by Burdorf et al: "The COVID-19 pandemic: one year later - an occupational perspective" (1) and "The COVID-19 (Coronavirus) pandemic: consequences for occupational health" (2). The authors highlight the importance of the societal consequences of the outbreak and changes in the world of work to manage occupational health. The key points identified - such as individual socio-economic factors, psychological effects and occupations with highest risk of contamination - modify return-to-work approaches. It is estimated that around 800 million people of working age worldwide were living with disabilities before the SARS-CoV-2 pandemic. In early January 2021, the cumulative COVID-19 hospitalisation rate reached 207.4/100 000 (18-49-year-olds) and 505.7/100 000 (50-64-year-olds), respectively, in the United States (3). In France, the hospitalisation rate was 411.5/100 000 across all ages (4). A recent cohort study of working-age men who were hospitalised for COVID-19 highlighted the long-term health consequences of such a disease (5). The SARS-CoV-2 pandemic creates new challenges for occupational health, shifting attention away from return-to-work after health problems to resuming work during an outbreak, dealing with lockdown, and taking special account of workers with vulnerabilities (6, 7). We recommend considering three different aspects of occupational medicine during a pandemic. Firstly, for most workers at high-risk of severe COVID-19, the issues of work disability and resuming work had never occurred before the epidemic. Recommendations such as physical and social distancing and wearing a facemask are highly advisable to protect against infection but may not be enough to enable some individuals to resume work. Therefore, decision-making requires individual comprehensive assessments of the underlying medical condition, the SARS-CoV-2 contamination risk associated with either regular work or teleworking, and vaccination opportunities. The second situation concerns workers who have suffered from COVID-19. Preliminary studies suggest that long recovery duration is related to high severity (7), but this is still a matter of debate for patients suffering from "long COVID-19" (5, 8, 9), a condition for which the long-term effects remain unknown. Any long-running recovery must be considered to be a potential sign of long COVID-19. These long-lasting syndromes occur among patients with severe symptoms but have also been reported independently of acute phase severity, hospitalisation and receiving medical oxygen (8, 9). Researchers worldwide are currently investigating such syndromes. Strategies promoting return to work for these workers will need to be implemented and could be similar to programmes developed for other chronic conditions. Moreover, numerous more serious sequelae following critical illness suggest the need for enhanced support by rehabilitation and occupational health specialists. Finally, the consequences of the epidemic must be evaluated over time for people who suffered from functional limitations before COVID-19 as their physical and mental condition may be modified by the epidemic and, specifically, the consequences of lockdown (10). In all of these situations, medical, social, financial and working contexts are key elements. In addition to a medical assessment, the use of scales such as the Work Ability Index (WAI) (11) or the Work Productivity and Activity Impairment (WPAI) (12) can help perform long-term follow-up and provide information about work capacity and workload. It also gives a "back to basics" perspective, urging politicians to move towards a `decent-work-for-all` policy, as advocated by the United Nation`s Sustainable Development Goal (SDG) 8, which the WHO has endorsed (13). References 1. Burdorf A, Porru F, Rugulies R. The COVID-19 pandemic: one year later - an occupational perspective. Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.3956 2. Burdorf A, Porru F, Rugulies R. The COVID-19 (Coronavirus) pandemic: consequences for occupational health. Scand J Work Environ Health. 2020;46(3):229-230. https://doi:org/10.5271/sjweh.3893. 3. COVID-19 Hospitalizations [Internet]. Available from: https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html 4. COVID-19 in France, vaccine and allergy management in occupational setting. Descatha A et al. Arch Mal Prof Environ 2021. Accepted for publication. 5. Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;397(10270):220-32 https://doi.org/10.1016/S0140-6736(20)32656-8 6. Shaw WS, Main CJ, Findley PA, Collie A, Kristman VL, Gross DP. Opening the Workplace After COVID-19: What Lessons Can be Learned from Return-to-Work Research? J Occup Rehabil. 2020;30(3):299-302. https://doi.org/10.1007/s10926-020-09908-9 7. Taylor T, Das R, Mueller K, Pransky G, Christian J, Orford R, et al. Safely Returning America to Work: Part I: General Guidance for Employers. J Occup Environ Med. 2020;62(9):771-9. https://doi.org/10.1097/JOM.0000000000001984 8. Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324(6):603-5. https://doi.org/10.1001/jama.2020.12603 9. Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR Morb Mortal Wkly. 2020;69(30):993-8. https://doi.org/10.15585/mmwr.mm6930e1 10. Chudasama YV, Gillies CL, Zaccardi F, Coles B, Davies MJ, Seidu S, et al. Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals. Diabetes Metab Syndr. 2020;14(5):965-7. https://doi.org/10.1016/j.dsx.2020.06.042 11. Tuomi K. Eleven-year follow-up of aging workers. Scand J Work Environ Health. 1997;23(1):1-71. 12. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4(5):353-65. https://doi.org/10.2165/00019053-199304050-00006 13. Organization WH. Health in the 2030 agenda for sustainable development. Sixty-Ninth World Health Assembly. Document A. 2016, p69.}, } @article {pmid34003184, year = {2021}, author = {Martini, N}, title = {[Long covid syndrome and real world evidence.].}, journal = {Recenti progressi in medicina}, volume = {112}, number = {5}, pages = {335-337}, doi = {10.1701/3608.35869}, pmid = {34003184}, issn = {2038-1840}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, abstract = {Long covid syndrome is increasingly studied and debated. The number of scientific publications is growing and groups and associations of patients affected by the syndrome are increasingly active. There is concern that international attention to this syndrome could lead to an excess of diagnostic procedures and unnecessary medical interventions. On the other hand, we have a robust body of evidence of a constellation of symptoms and ailments suffered by patients recovered from covid-19. Tackling this problem therefore means tackling coexistence with covid-19 in the long term, annexing this pathology in a chronic perspective. The collection and analysis of data, therefore, could already allow a stratification of populations at risk, putting social and services in a position to respond adequately to the demand for assistance that is expected to be received by a very large number of patients. But it is essential that real-world evidence goes hand in hand with the selection, analysis and interpretation of information collected in administrative databases, disease registers and databases developed by universities and institutions to promote public health truly personalized.}, } @article {pmid34002281, year = {2021}, author = {Angus-Leppan, H and Guiloff, AE and Benson, K and Guiloff, RJ}, title = {Navigating migraine care through the COVID-19 pandemic: an update.}, journal = {Journal of neurology}, volume = {268}, number = {11}, pages = {4388-4395}, pmid = {34002281}, issn = {1432-1459}, mesh = {*COVID-19/complications ; Communicable Disease Control ; Humans ; *Migraine Disorders/epidemiology/therapy ; Pandemics ; Quality of Life ; Post-Acute COVID-19 Syndrome ; }, abstract = {The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19-older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression-are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID.}, } @article {pmid34000678, year = {2021}, author = {Frontera, JA and Yang, D and Lewis, A and Patel, P and Medicherla, C and Arena, V and Fang, T and Andino, A and Snyder, T and Madhavan, M and Gratch, D and Fuchs, B and Dessy, A and Canizares, M and Jauregui, R and Thomas, B and Bauman, K and Olivera, A and Bhagat, D and Sonson, M and Park, G and Stainman, R and Sunwoo, B and Talmasov, D and Tamimi, M and Zhu, Y and Rosenthal, J and Dygert, L and Ristic, M and Ishii, H and Valdes, E and Omari, M and Gurin, L and Huang, J and Czeisler, BM and Kahn, DE and Zhou, T and Lin, J and Lord, AS and Melmed, K and Meropol, S and Troxel, AB and Petkova, E and Wisniewski, T and Balcer, L and Morrison, C and Yaghi, S and Galetta, S}, title = {A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.}, journal = {Journal of the neurological sciences}, volume = {426}, number = {}, pages = {117486}, pmid = {34000678}, issn = {1878-5883}, support = {P01 AG060882/AG/NIA NIH HHS/United States ; P30 AG066512/AG/NIA NIH HHS/United States ; }, mesh = {Activities of Daily Living ; *COVID-19 ; Humans ; Prospective Studies ; Quality of Life ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Little is known regarding long-term outcomes of patients hospitalized with COVID-19.

METHODS: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.

RESULTS: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups.

CONCLUSIONS: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.}, } @article {pmid33998773, year = {2022}, author = {Rasile, M and Lauranzano, E and Mirabella, F and Matteoli, M}, title = {Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies.}, journal = {The FEBS journal}, volume = {289}, number = {12}, pages = {3374-3392}, pmid = {33998773}, issn = {1742-4658}, mesh = {Animals ; Brain ; *COVID-19 ; Female ; Humans ; *Mental Disorders ; Pregnancy ; *Pregnancy Complications, Infectious ; *Prenatal Exposure Delayed Effects ; }, abstract = {Intragravidic and perinatal infections, acting through either direct viral effect or immune-mediated responses, are recognized causes of liability for neurodevelopmental disorders in the progeny. The large amounts of epidemiological data and the wealth of information deriving from animal models of gestational infections have contributed to delineate, in the last years, possible underpinning mechanisms for this phenomenon, including defects in neuronal migration, impaired spine and synaptic development, and altered activation of microglia. Recently, dysfunctions of the neurovascular unit and anomalies of the brain vasculature have unexpectedly emerged as potential causes at the origin of behavioral abnormalities and psychiatric disorders consequent to prenatal and perinatal infections. This review aims to discuss the up-to-date literature evidence pointing to the neurovascular unit and brain vasculature damages as the etiological mechanisms in neurodevelopmental syndromes. We focus on the inflammatory events consequent to intragravidic viral infections as well as on the direct viral effects as the potential primary triggers. These authors hope that a timely review of the literature will help to envision promising research directions, also relevant for the present and future COVID-19 longitudinal studies.}, } @article {pmid33993490, year = {2022}, author = {Plassmeyer, M and Alpan, O and Corley, MJ and Premeaux, TA and Lillard, K and Coatney, P and Vaziri, T and Michalsky, S and Pang, APS and Bukhari, Z and Yeung, ST and Evering, TH and Naughton, G and Latterich, M and Mudd, P and Spada, A and Rindone, N and Loizou, D and Ulrik Sønder, S and Ndhlovu, LC and Gupta, R}, title = {Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID.}, journal = {Allergy}, volume = {77}, number = {1}, pages = {118-129}, pmid = {33993490}, issn = {1398-9995}, support = {K01 HL140271/HL/NHLBI NIH HHS/United States ; }, mesh = {CD4-Positive T-Lymphocytes ; *COVID-19/complications ; Caspase 1 ; Caspase 3 ; Caspase 7 ; *Caspase Inhibitors/therapeutic use ; Caspases/genetics ; Humans ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {BACKGROUND: COVID-19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long-term sequela.

AIMS: Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease.

MATERIALS & METHODS: We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subject presenting with various comorbid conditions served as controls.

RESULTS: Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared with unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed upregulated caspase-1activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7levels in red blood cells from COVID-19 patients compared with controls that was reduced following caspase inhibition.

DISCUSSION: Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed.

CONCLUSION: Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.}, } @article {pmid33992951, year = {2021}, author = {Llach, CD and Vieta, E}, title = {Mind long COVID: Psychiatric sequelae of SARS-CoV-2 infection.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {49}, number = {}, pages = {119-121}, pmid = {33992951}, issn = {1873-7862}, mesh = {Brain/pathology ; COVID-19/*complications/diagnosis/etiology/psychology ; *Disease Progression ; Humans ; Mental Disorders/*diagnosis/etiology/psychology ; Nervous System Diseases/*diagnosis/etiology/psychology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33992686, year = {2021}, author = {Korompoki, E and Gavriatopoulou, M and Hicklen, RS and Ntanasis-Stathopoulos, I and Kastritis, E and Fotiou, D and Stamatelopoulos, K and Terpos, E and Kotanidou, A and Hagberg, CA and Dimopoulos, MA and Kontoyiannis, DP}, title = {Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review.}, journal = {The Journal of infection}, volume = {83}, number = {1}, pages = {1-16}, pmid = {33992686}, issn = {1532-2742}, mesh = {*COVID-19/complications ; Humans ; Pandemics ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: "Long COVID", a term coined by COVID-19 survivors, describes persistent or new symptoms in a subset of patients who have recovered from acute illness. Globally, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating the need for a more thorough understanding of the array of potential sequelae of COVID-19. The multisystemic aspects of acute COVID-19 have been the subject of intense investigation, but the long-term complications remain poorly understood. Emerging data from lay press, social media, commentaries, and emerging scientific reports suggest that some COVID-19 survivors experience organ impairment and/or debilitating chronic symptoms, at times protean in nature, which impact their quality of life.

METHODS/RESULTS: In this review, by addressing separately each body system, we describe the pleiotropic manifestations reported post COVID-19, their putative pathophysiology and risk factors, and attempt to offer guidance regarding work-up, follow-up and management strategies. Long term sequelae involve all systems with a negative impact on mental health, well-being and quality of life, while a subset of patients, report debilitating chronic fatigue, with or without other fluctuating or persistent symptoms, such as pain or cognitive dysfunction. Although the pathogenesis is unclear, residual damage from acute infection, persistent immune activation, mental factors, or unmasking of underlying co-morbidities are considered as drivers. Comparing long COVID with other post viral chronic syndromes may help to contextualize the complex somatic and emotional sequalae of acute COVID-19. The pace of recovery of different aspects of the syndrome remains unclear as the pandemic began only a year ago.

CONCLUSIONS: Early recognition of long-term effects and thorough follow-up through dedicated multidisciplinary outpatient clinics with a carefully integrated research agenda are essential for treating COVID-19 survivors holistically.}, } @article {pmid33990122, year = {2021}, author = {Crea, F}, title = {The central role of amygdala in stress-related cardiac diseases and an update on long-COVID.}, journal = {European heart journal}, volume = {42}, number = {19}, pages = {1813-1817}, doi = {10.1093/eurheartj/ehab255}, pmid = {33990122}, issn = {1522-9645}, mesh = {Amygdala ; *COVID-19 ; *Heart Diseases ; Humans ; SARS-CoV-2 ; Stress, Psychological ; }, } @article {pmid33987484, year = {2021}, author = {McCorkell, L and S Assaf, G and E Davis, H and Wei, H and Akrami, A}, title = {Patient-Led Research Collaborative: embedding patients in the Long COVID narrative.}, journal = {Pain reports}, volume = {6}, number = {1}, pages = {e913}, pmid = {33987484}, issn = {2471-2531}, abstract = {A large subset of patients with coronavirus disease 2019 (COVID-19) are experiencing symptoms well beyond the claimed 2-week recovery period for mild cases. These long-term sequelae have come to be known as Long COVID. Originating out of a dedicated online support group, a team of patients formed the Patient-Led Research Collaborative and conducted the first research on Long COVID experience and symptoms. This article discusses the history and value of patient-centric and patient-led research; the formation of Patient-Led Research Collaborative as well as key findings to date; and calls for the following: the acknowledgement of Long COVID as an illness, an accurate estimate of the prevalence of Long COVID, publicly available basic symptom management, care, and research to not be limited to those with positive polymerase chain reaction and antibody tests, and aggressive research and investigation into the pathophysiology of symptoms.}, } @article {pmid33987042, year = {2021}, author = {Dayrit, JK and Verduzco-Gutierrez, M and Teal, A and Shah, SA}, title = {Enhanced External Counterpulsation as a Novel Treatment for Post-acute COVID-19 Sequelae.}, journal = {Cureus}, volume = {13}, number = {4}, pages = {e14358}, pmid = {33987042}, issn = {2168-8184}, abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. As patients recover from COVID-19, some continue to report persisting symptoms weeks to months after acute infection. These effects have been referred to as post-acute sequelae of SARS-CoV-2 infection (PASC). We report the case of a 38-year-old woman suffering from PASC symptoms following acute COVID-19 in October 2020. During her acute infection phase, she had a home recovery and reported her predominant symptoms as fatigue, headaches, body pain, and shortness of breath. After most of her symptoms were resolved, she continued to have periodic episodes of fatigue and headaches, along with random shortness of breath while at rest and during activities for months beyond the acute phase of the illness. She also noted the presence of "brain fog," as if lacking the same clarity that she had prior to her illness. These symptoms persisted for three months before the patient underwent enhanced external counterpulsation (EECP) therapy in one-hour sessions, three times per week. This therapy was chosen based on the mechanism of action of EECP benefiting patients with ischemic cardiovascular diseases. After one week, her "brain fog" had improved, with shortness of breath improving after 1.5 weeks. The patient reported returning to pre-COVID health and fitness after approximately five weeks of EECP treatment. To our knowledge, this is the first case of using EECP for post-COVID shortness of breath, fatigue, and "brain fog."}, } @article {pmid33985343, year = {2021}, author = {Cumpstey, AF and Clark, AD and Santolini, J and Jackson, AA and Feelisch, M}, title = {COVID-19: A Redox Disease-What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment.}, journal = {Antioxidants & redox signaling}, volume = {35}, number = {14}, pages = {1226-1268}, doi = {10.1089/ars.2021.0017}, pmid = {33985343}, issn = {1557-7716}, mesh = {COVID-19/diagnosis/*immunology ; Humans ; Oxidation-Reduction ; *Pandemics ; *COVID-19 Drug Treatment ; }, abstract = {Significance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking. Recent Advances: Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress. Critical Issues: We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level. Future Directions: While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID. Antioxid. Redox Signal. 35, 1226-1268.}, } @article {pmid33984263, year = {2021}, author = {Lund, LC and Hallas, J and Nielsen, H and Koch, A and Mogensen, SH and Brun, NC and Christiansen, CF and Thomsen, RW and Pottegård, A}, title = {Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {10}, pages = {1373-1382}, pmid = {33984263}, issn = {1474-4457}, mesh = {Adolescent ; Adult ; COVID-19/*complications/*epidemiology ; Cohort Studies ; Denmark/epidemiology ; Female ; Hospitalization ; Humans ; Male ; Middle Aged ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Individuals admitted to hospital for COVID-19 might have persisting symptoms (so-called long COVID) and delayed complications after discharge. However, little is known regarding the risk for those not admitted to hospital. We therefore examined prescription drug and health-care use after SARS-CoV-2 infection not requiring hospital admission.

METHODS: This was a population-based cohort study using the Danish prescription, patient, and health insurance registries. All individuals with a positive or negative RT-PCR test for SARS-CoV-2 in Denmark between Feb 27 and May 31, 2020, were eligible for inclusion. Outcomes of interest were delayed acute complications, chronic disease, hospital visits due to persisting symptoms, and prescription drug use. We used data from non-hospitalised SARS-CoV-2-positive and matched SARS-CoV-2-negative individuals from 2 weeks to 6 months after a SARS-CoV-2 test to obtain propensity score-weighted risk differences (RDs) and risk ratios (RRs) for initiation of 14 drug groups and 27 hospital diagnoses indicative of potential post-acute effects. We also calculated prior event rate ratio-adjusted rate ratios of overall health-care use. This study is registered in the EU Electronic Register of Post-Authorisation Studies (EUPAS37658).

FINDINGS: 10 498 eligible individuals tested positive for SARS-CoV-2 in Denmark from Feb 27 to May 31, 2020, of whom 8983 (85·6%) were alive and not admitted to hospital 2 weeks after their positive test. The matched SARS-CoV-2-negative reference population not admitted to hospital consisted of 80 894 individuals. Compared with SARS-CoV-2-negative individuals, SARS-CoV-2-positive individuals were not at an increased risk of initiating new drugs (RD <0·1%) except bronchodilating agents, specifically short-acting β2-agonists (117 [1·7%] of 6935 positive individuals vs 743 [1·3%] of 57 206 negative individuals; RD +0·4% [95% CI 0·1-0·7]; RR 1·32 [1·09-1·60]) and triptans (33 [0·4%] of 8292 vs 198 [0·3%] of 72 828; RD +0·1% [0·0-0·3]; RR 1·55 [1·07-2·25]). There was an increased risk of receiving hospital diagnoses of dyspnoea (103 [1·2%] of 8676 vs 499 [0·7%] of 76 728; RD +0·6% [0·4-0·8]; RR 2·00 [1·62-2·48]) and venous thromboembolism (20 [0·2%] of 8785 vs 110 [0·1%] of 78 872; RD +0·1% [0·0-0·2]; RR 1·77 [1·09-2·86]) for SARS-CoV-2-positive individuals compared with negative individuals, but no increased risk of other diagnoses. Prior event rate ratio-adjusted rate ratios of overall general practitioner visits (1·18 [95% CI 1·15-1·22]) and outpatient hospital visits (1·10 [1·05-1·16]), but not hospital admission, showed increases among SARS-CoV-2-positive individuals compared with SARS-CoV-2-negative individuals.

INTERPRETATION: The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission is low. However, increases in visits to general practitioners and outpatient hospital visits could indicate COVID-19 sequelae.

FUNDING: None.}, } @article {pmid33983522, year = {2021}, author = {Chilazi, M and Duffy, EY and Thakkar, A and Michos, ED}, title = {COVID and Cardiovascular Disease: What We Know in 2021.}, journal = {Current atherosclerosis reports}, volume = {23}, number = {7}, pages = {37}, pmid = {33983522}, issn = {1534-6242}, support = {Amato Fund in Women's Cardiovascular Health//Johns Hopkins University/ ; }, mesh = {Athletes ; COVID-19/blood/*complications/rehabilitation/virology ; Cardiovascular Diseases/*diagnostic imaging/*etiology/virology ; Humans ; Magnetic Resonance Imaging/methods ; Prognosis ; *Return to Sport ; *SARS-CoV-2 ; Severity of Illness Index ; Troponin/blood ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has been the cause of significant global morbidity and mortality. Here, we review the literature to date of the short-term and long-term consequences of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the heart.

RECENT FINDINGS: Early case reports described a spectrum of cardiovascular manifestations of COVID-19, including myocarditis, stress cardiomyopathy, myocardial infarction, and arrhythmia. However, in most cases, myocardial injury in COVID-19 appears to be predominantly mediated by the severity of critical illness rather than direct injury to myocardium from viral particles. While cardiac magnetic resonance imaging remains a powerful tool for diagnosing acute myocarditis, it should be used judiciously in light of low baseline prevalence of myocarditis. Guiding an athletic patient through return to play (RTP) after COVID-19 infection is a challenging process. More recent data show RTP has been a safe endeavor using a screening protocol. "Long COVID" or post-acute sequelae of SARS-CoV-2 infection has also been described. The reported symptoms span a large breadth of cardiopulmonary and neurologic complaints including fatigue, palpitations, chest pain, breathlessness, brain fog, and dysautonomia including postural tachycardia syndrome (POTS). Management of POTS/dysautonomia primarily centers on education, exercise, and salt and fluid repletion. Our understanding of the impact of COVID-19 on the cardiovascular system is constantly evolving. As we enter a new age of survivorship, additional research is needed to catalogue the burden of persistent cardiopulmonary symptoms. Research is also needed to learn how acute management may alter the likelihood and prevalence of this chronic syndrome.}, } @article {pmid33983062, year = {2021}, author = {Lees, VC and Wong, JKF and Ibrahim, I}, title = {Critical ischaemia of the hand and upper limb in a patient with long COVID-19 infection.}, journal = {The Journal of hand surgery, European volume}, volume = {46}, number = {6}, pages = {684-686}, pmid = {33983062}, issn = {2043-6289}, mesh = {*COVID-19/complications ; Humans ; Ischemia/etiology ; SARS-CoV-2 ; Upper Extremity ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33977626, year = {2021}, author = {Cabrera Martimbianco, AL and Pacheco, RL and Bagattini, ÂM and Riera, R}, title = {Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review.}, journal = {International journal of clinical practice}, volume = {75}, number = {10}, pages = {e14357}, pmid = {33977626}, issn = {1742-1241}, support = {//Sociedade Beneficente de Senhoras Hospital Sírio-Libanês/ ; }, mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Dyspnea/diagnosis/epidemiology/etiology ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {AIMS: To identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID-19 (post-acute COVID-19 syndrome), its clinical manifestations, and the criteria used for diagnosis.

METHODS: Systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non-comparative studies, cross-sectional, before-and-after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID-19, signs and symptoms, criteria used for diagnosis, and potential risk factors.

RESULTS: We included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID-19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID-19 varied from 3 to 24 weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms.

CONCLUSION: The frequency of long COVID-19 reached up to 80% over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.}, } @article {pmid33976591, year = {2021}, author = {Leviner, S}, title = {Recognizing the Clinical Sequelae of COVID-19 in Adults: COVID-19 Long-Haulers.}, journal = {The journal for nurse practitioners : JNP}, volume = {17}, number = {8}, pages = {946-949}, pmid = {33976591}, issn = {1555-4155}, abstract = {As the numbers of acute severe acute respiratory syndrome coronavirus 2 infections continue to rise, we are learning that symptoms do not resolve quickly in all patients. Although why some patients experience persistent symptoms is not clear, these individuals suffer. Long-hauler is the term that is associated with these persistent symptoms, and this review of the literature provides information to nurse practitioners working in primary care about symptoms, risk factors, and resources for disease management.}, } @article {pmid33975372, year = {2021}, author = {Volk, GF and Kuttenreich, AM and Geitner, M and Guntinas-Lichius, O}, title = {[Acute facial paresis as a possible complication of vaccination against SARS-CoV-2].}, journal = {Laryngo- rhino- otologie}, volume = {100}, number = {7}, pages = {526-528}, doi = {10.1055/a-1501-0470}, pmid = {33975372}, issn = {1438-8685}, mesh = {*Bell Palsy ; *COVID-19/complications ; COVID-19 Vaccines/*adverse effects ; Facial Nerve ; *Facial Paralysis/chemically induced ; Humans ; *Vaccination/adverse effects ; Post-Acute COVID-19 Syndrome ; }, abstract = {Although acute facial nerve palsy (Bell's palsy) is explicitly mentioned in the information sheets for vaccines as a possible complication of vaccination against SARS-CoV-2, from our point of view the benefits of the vaccination clearly outweigh the possible risks. At most, if at all, a slightly increased risk can be derived from the previous case reports. In general, the risk of acute facial palsy is described in association with many vaccinations. The risk, if any, does not appear to be a specific risk of SARS-CoV-2 vaccines. On the other hand, cases of acute facial palsy as symptom of a COVID-19 disease have also been described, so that the theoretical question arises as to the extent to which the vaccination may prevent rather than promote the occurrence of facial palsy. Ultimately, if acted quickly, acute facial paralysis can be treated well and its severity and sequelae cannot be compared with the severity of a COVID-19 disease and its possible long-COVID sequelae.}, } @article {pmid33973880, year = {2022}, author = {Sykora, D and Stonnington, CM and Jain, N}, title = {An Agitated Patient With COVID-19 Infection and Early-onset Alzheimer Disease.}, journal = {Alzheimer disease and associated disorders}, volume = {36}, number = {1}, pages = {83-84}, pmid = {33973880}, issn = {1546-4156}, mesh = {*Alzheimer Disease/complications/diagnosis ; Benzodiazepines ; *COVID-19/complications ; Humans ; Male ; Middle Aged ; Psychomotor Agitation ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Encephalopathy, delirium, and agitation are documented symptoms of coronavirus disease (COVID-19) infection, but research into the management of agitation in the setting of COVID-19 and pre-existing neuropsychiatric disease is ongoing. We present a 55-year-old male patient with early-onset Alzheimer disease and deteriorating mental and functional status who presented to our institution with agitation and persistent COVID-19 positivity on polymerase chain reaction testing. His agitation was improved through pharmacologic optimization including the avoidance of benzodiazepines and initiation of clonidine and prazosin, which temporally coincided with the resolution of his nearly 2-month long COVID-19 positivity.}, } @article {pmid33971585, year = {2021}, author = {Wang, JY and Zhang, W and Roehrl, MW and Roehrl, VB and Roehrl, MH}, title = {An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19.}, journal = {Journal of autoimmunity}, volume = {120}, number = {}, pages = {102644}, pmid = {33971585}, issn = {1095-9157}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R21 CA251992/CA/NCI NIH HHS/United States ; }, mesh = {A549 Cells ; Autoantigens/*immunology ; *Autoimmunity ; COVID-19/*immunology/pathology ; Humans ; Lung/*immunology/pathology/virology ; SARS-CoV-2/*physiology ; Signal Transduction/*immunology ; Virus Replication/*immunology ; }, abstract = {We aim to establish a comprehensive COVID-19 autoantigen atlas in order to understand autoimmune diseases caused by SARS-CoV-2 infection. Based on the unique affinity between dermatan sulfate and autoantigens, we identified 348 proteins from human lung A549 cells, of which 198 are known targets of autoantibodies. Comparison with current COVID data identified 291 proteins that are altered at protein or transcript level in SARS-CoV-2 infection, with 191 being known autoantigens. These known and putative autoantigens are significantly associated with viral replication and trafficking processes, including gene expression, ribonucleoprotein biogenesis, mRNA metabolism, translation, vesicle and vesicle-mediated transport, and apoptosis. They are also associated with cytoskeleton, platelet degranulation, IL-12 signaling, and smooth muscle contraction. Host proteins that interact with and that are perturbed by viral proteins are a major source of autoantigens. Orf3 induces the largest number of protein alterations, Orf9 affects the mitochondrial ribosome, and they and E, M, N, and Nsp proteins affect protein localization to membrane, immune responses, and apoptosis. Phosphorylation and ubiquitination alterations by viral infection define major molecular changes in autoantigen origination. This study provides a large list of autoantigens as well as new targets for future investigation, e.g., UBA1, UCHL1, USP7, CDK11A, PRKDC, PLD3, PSAT1, RAB1A, SLC2A1, platelet activating factor acetylhydrolase, and mitochondrial ribosomal proteins. This study illustrates how viral infection can modify host cellular proteins extensively, yield diverse autoantigens, and trigger a myriad of autoimmune sequelae. Our work provides a rich resource for studies into "long COVID" and related autoimmune sequelae.}, } @article {pmid33953912, year = {2020}, author = {Duncan, E and Cooper, K and Cowie, J and Alexander, L and Morris, J and Preston, J}, title = {A national survey of community rehabilitation service provision for people with long Covid in Scotland.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {1416}, pmid = {33953912}, issn = {2046-1402}, support = {COV/LTE/20/29/CSO_/Chief Scientist Office/United Kingdom ; }, mesh = {*COVID-19 ; Cost-Benefit Analysis ; Humans ; SARS-CoV-2 ; Scotland ; Surveys and Questionnaires ; }, abstract = {Background: Over 50 million cases of COVID-19 have been confirmed globally as of November 2020. Evidence is rapidly emerging on the epidemiology of COVID-19, and its impact on individuals and potential burden on health services and society. Between 10-35% of people with COVID-19 may experience post-acute long Covid. This currently equates to between 8,129 and 28,453 people in Scotland. Some of these people will require rehabilitation to support their recovery. Currently, we do not know how to optimally configure community rehabilitation services for people with long Covid. Methods: This national survey aimed to provide a detailed description of current community rehabilitation provision for people with long Covid in Scotland. We developed, piloted, and conducted a national electronic survey of current community rehabilitation service provision for people presenting with long Covid symptomatology. Our sample were the Allied Health Professions Directors of all 14 territorial NHS Health Boards in Scotland. Fixed response and narrative data were analysed descriptively. Results: Responses were received from all respondents (14/14), enabling a national picture to be gained. Almost all Health Boards (13/14) currently deliver rehabilitation for people with long Covid within pre-existing services. Fatigue (11/14) and respiratory conditions (9/14) were the two most common presenting problems of patients. Most long Covid community rehabilitation services are delivered through a combination of face-to-face and digital contact (13/14). Conclusions: Community rehabilitation for people with long Covid is an emerging reality. This survey provides a national picture of current community rehabilitation for people with long Covid. We do not know how community rehabilitation can be optimally delivered for this population. This is vital as community rehabilitation services were already under pressure prior to the emergence of COVID-19. Further research is urgently required to investigate the implementation, outcomes and cost-effectiveness of differing models of community rehabilitation for this patient population.}, } @article {pmid33966266, year = {2021}, author = {Iyengar, KP and Jain, VK and Vaishya, R and Ish, P}, title = {Long COVID-19: an emerging pandemic in itself.}, journal = {Advances in respiratory medicine}, volume = {89}, number = {2}, pages = {234-236}, doi = {10.5603/ARM.a2021.0040}, pmid = {33966266}, issn = {2543-6031}, mesh = {COVID-19/*complications/etiology/*rehabilitation ; Cognitive Dysfunction/etiology ; Continuity of Patient Care/organization & administration ; Fatigue/etiology ; Humans ; Nervous System Diseases/etiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33962805, year = {2021}, author = {Pavli, A and Theodoridou, M and Maltezou, HC}, title = {Post-COVID Syndrome: Incidence, Clinical Spectrum, and Challenges for Primary Healthcare Professionals.}, journal = {Archives of medical research}, volume = {52}, number = {6}, pages = {575-581}, pmid = {33962805}, issn = {1873-5487}, mesh = {*COVID-19/complications/diagnosis ; Humans ; Incidence ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; }, abstract = {Post-COVID syndrome also known as long COVID refers to symptoms persisting for more than three weeks after the diagnosis of COVID-19. We reviewed the current evidence on post-COVID syndrome, focusing on its clinical manifestations and addressing the challenges for its management in primary healthcare. The incidence of post-COVID syndrome is estimated at 10-35%, while for hospitalized patients it may reach 85%. Fatigue is the most common symptom reported in 17.5-72% of post-COVID cases, followed by residual dyspnea with an incidence ranging from 10-40%. Mental problems, chest pain, and olfactory and gustatory dysfunction may affect up to 26, 22 and 11% of patients, respectively. More than one third of patients with post-COVID syndrome have pre-existing comorbidities, hypertension and diabetes mellitus being the most common. Beyond the prolonged duration of symptoms, the scarce published data indicate that most patients with post-COVID syndrome have a good prognosis with no further complications or fatal outcomes reported. Given the clinical spectrum of patients with post-COVID syndrome, most of them will be managed by primary healthcare professionals, in conjunction with pre-existing or new co-morbidities, which, in turn, may increase the burden of COVID-19 on primary healthcare. In conclusion approximately 10% of patients with COVID-19 may have symptoms persisting beyond three weeks, fulfilling the criteria of post-COVID syndrome. Primary healthcare professionals have a key role in the management of patients with post-COVID syndrome. Research is needed to elucidate the pathogenesis, clinical spectrum, and prognosis of post-COVID syndrome.}, } @article {pmid33961259, year = {2021}, author = {Jebrini, T and Reinhard, MA and Ortmann, M and Strupf, M and Rüb, M and Padberg, F and Adorjan, K}, title = {[Psychiatric complications of COVID-19: The unknown disease (Long Covid)].}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {9}, pages = {48-50}, doi = {10.1007/s15006-021-9888-5}, pmid = {33961259}, issn = {1613-3560}, mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; }, } @article {pmid33948602, year = {2021}, author = {Estiri, H and Strasser, ZH and Brat, GA and Semenov, YR and , and Patel, CJ and Murphy, SN}, title = {Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2021.04.25.21255923}, pmid = {33948602}, support = {MC_PC_18034/MRC_/Medical Research Council/United Kingdom ; T15 LM007092/LM/NLM NIH HHS/United States ; }, abstract = {For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. In this retrospective electronic health records (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston metropolitan area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records two months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR: 2.60, 95% CI [1.94 - 3.46]), alopecia (OR: 3.09, 95% CI [2.53 - 3.76]), chest pain (OR: 1.27, 95% CI [1.09 - 1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22 - 1.64]), pneumonia (OR 1.66, 95% CI [1.28 - 2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22 - 1.64]) are some of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. Our approach avoids a flood of false positive discoveries while offering a more robust probabilistic approach compared to the standard linear phenome-wide association study (PheWAS). The findings of this study confirm many of the post-COVID symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63 percent of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.}, } @article {pmid33948596, year = {2021}, author = {Donowitz, M and Tse, CM and Dokladny, K and Rawat, M and Horwitz, I and Ye, C and Kell, A and Lin, R and Lee, S and Guo, C and Tsai, SJ and Cox, A and Gould, S and In, J and Bradfute, S and Zachos, NC and Kovbasnjuk, O}, title = {SARS-COV-2 induced Diarrhea is inflammatory, Ca [2+] Dependent and involves activation of calcium activated Cl channels.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2021.04.27.441695}, pmid = {33948596}, issn = {2692-8205}, abstract = {Diarrhea occurs in 2-50% of cases of COVID-19 (∼8% is average across series). The diarrhea does not appear to account for the disease mortality and its contribution to the morbidity has not been defined, even though it is a component of Long Covid or post-infectious aspects of the disease. Even less is known about the pathophysiologic mechanism of the diarrhea. To begin to understand the pathophysiology of COVID-19 diarrhea, we exposed human enteroid monolayers obtained from five healthy subjects and made from duodenum, jejunum, and proximal colon to live SARS-CoV-2 and virus like particles (VLPs) made from exosomes expressing SARS-CoV-2 structural proteins (Spike, Nucleocapsid, Membrane and Envelope). Results: 1) Live virus was exposed apically for 90 min, then washed out and studied 2 and 5 days later. SARS-Cov-2 was taken up by enteroids and live virus was present in lysates and in the apical>>basolateral media of polarized enteroids 48 h after exposure. This is the first demonstration of basolateral appearance of live virus after apical exposure. High vRNA concentration was detected in cell lysates and in the apical and basolateral media up to 5 days after exposure. 2) Two days after viral exposure, cytokine measurements of media showed significantly increased levels of IL-6, IL-8 and MCP-1. 3) Two days after viral exposure, mRNA levels of ACE2, NHE3 and DRA were reduced but there was no change in mRNA of CFTR. NHE3 protein was also decreased. 4) Live viral studies were mimicked by some studies with VLP exposure for 48 h. VLPs with Spike-D614G bound to the enteroid apical surface and was taken up; this resulted in decreased mRNA levels of ACE2, NHE3, DRA and CFTR. 4) VLP effects were determined on active anion secretion measured with the Ussing chamber/voltage clamp technique. S-D614G acutely exposed to apical surface of human ileal enteroids did not alter the short-circuit current (Isc). However, VLPS-D614G exposure to enteroids that were pretreated for ∼24 h with IL-6 plus IL-8 induced a concentration dependent increase in Isc indicating stimulated anion secretion, that was delayed in onset by ∼8 min. The anion secretion was inhibited by apical exposure to a specific calcium activated Cl channel (CaCC) inhibitor (AO1) but not by a specific CFTR inhibitor (BP027); was inhibited by basolateral exposure to the K channel inhibit clortimazole; and was prevented by pretreatment with the calcium buffer BAPTA-AM. 5) The calcium dependence of the VLP-induced increase in Isc was studied in Caco-2/BBe cells stably expressing the genetically encoded Ca2+ sensor GCaMP6s. 24 h pretreatment with IL-6/IL-8 did not alter intracellular Ca2+. However, in IL-6/IL-8 pretreated cells, VLP S-D614G caused appearance of Ca [2+] waves and an overall increase in intracellular Ca [2+] with a delay of ∼10 min after VLP addition. We conclude that the diarrhea of COVID-19 appears to an example of a calcium dependent inflammatory diarrhea that involves both acutely stimulated Ca2+ dependent anion secretion (stimulated Isc) that involves CaCC and likely inhibition of neutral NaCl absorption (decreased NHE3 protein and mRNA and decreased DRA mRNA).}, } @article {pmid33939462, year = {2021}, author = {Holdoway, A}, title = {Addressing nutrition in the road map of recovery for those with long COVID-19.}, journal = {British journal of community nursing}, volume = {26}, number = {5}, pages = {218-222}, doi = {10.12968/bjcn.2021.26.5.218}, pmid = {33939462}, issn = {1462-4753}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/*diet therapy/*nursing ; Diet Therapy/*methods ; Female ; Humans ; Male ; Malnutrition/*nursing/*prevention & control ; Middle Aged ; *Nurse's Role ; Nursing Care/*standards ; Nutritional Status ; Practice Guidelines as Topic ; Recovery of Function/physiology ; SARS-CoV-2 ; }, } @article {pmid33930983, year = {2021}, author = {Décary, S and Gaboury, I and Poirier, S and Garcia, C and Simpson, S and Bull, M and Brown, D and Daigle, F}, title = {Humility and Acceptance: Working Within Our Limits With Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.}, journal = {The Journal of orthopaedic and sports physical therapy}, volume = {51}, number = {5}, pages = {197-200}, doi = {10.2519/jospt.2021.0106}, pmid = {33930983}, issn = {1938-1344}, mesh = {COVID-19/*complications ; Exercise Therapy/adverse effects ; Fatigue/*etiology/*therapy ; Fatigue Syndrome, Chronic/*etiology/*therapy ; Humans ; Quality of Life ; Rest ; }, abstract = {The term long COVID was coined by patients to describe the long-term consequences of COVID-19. One year into the pandemic, it was clear that all patients-those hospitalized with COVID-19 and those who lived with the disease in the community-were at risk of developing debilitating sequelae that would impact their quality of life. Patients with long COVID asked for rehabilitation. Many of them, including previously healthy and fit clinicians, tried to fight postviral fatigue with exercise-based rehabilitation. We observed a growing number of patients with long COVID who experienced adverse effects from exercise therapy and symptoms strikingly similar to those of myalgic encephalomyelitis (ME). Community-based physical therapists, including those in private practice, unaware of safety issues, are preparing to help an influx of patients with long COVID. In this editorial, we expose growing concerns about long COVID and ME. We issue safety recommendations for rehabilitation and share resources to improve care for those with postviral illnesses. J Orthop Sports Phys Ther 2021;51(5):197-200. doi:10.2519/jospt.2021.0106.}, } @article {pmid33926872, year = {2021}, author = {Simpson, F and Chew-Graham, C and Lokugamage, A}, title = {Long COVID in children: the perspectives of parents and children need to be heard.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {706}, pages = {216}, pmid = {33926872}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Child ; Humans ; Parents ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33925784, year = {2021}, author = {Wong, TL and Weitzer, DJ}, title = {Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {5}, pages = {}, pmid = {33925784}, issn = {1648-9144}, mesh = {Humans ; *COVID-19 ; *Fatigue Syndrome, Chronic/diagnosis ; Research Design ; SARS-CoV-2 ; }, abstract = {Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.}, } @article {pmid33923972, year = {2021}, author = {Sisó-Almirall, A and Brito-Zerón, P and Conangla Ferrín, L and Kostov, B and Moragas Moreno, A and Mestres, J and Sellarès, J and Galindo, G and Morera, R and Basora, J and Trilla, A and Ramos-Casals, M and On Behalf Of The CAMFiC Long Covid-Study Group, }, title = {Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {8}, pages = {}, pmid = {33923972}, issn = {1660-4601}, mesh = {*COVID-19 ; Disease Management ; Humans ; Primary Health Care ; SARS-CoV-2 ; }, abstract = {Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors' clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.}, } @article {pmid33919537, year = {2021}, author = {Silva Andrade, B and Siqueira, S and de Assis Soares, WR and de Souza Rangel, F and Santos, NO and Dos Santos Freitas, A and Ribeiro da Silveira, P and Tiwari, S and Alzahrani, KJ and Góes-Neto, A and Azevedo, V and Ghosh, P and Barh, D}, title = {Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms.}, journal = {Viruses}, volume = {13}, number = {4}, pages = {}, pmid = {33919537}, issn = {1999-4915}, mesh = {COVID-19/*complications/*physiopathology ; Cardiovascular System ; Diarrhea ; Guillain-Barre Syndrome ; Hemostasis ; Humans ; Immune System ; Inflammation ; Mental Health ; Nervous System ; Pandemics ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome ; Systemic Inflammatory Response Syndrome/*complications/*physiopathology ; Thrombosis ; }, abstract = {The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.}, } @article {pmid33914346, year = {2021}, author = {Saini, G and Aneja, R}, title = {Cancer as a prospective sequela of long COVID-19.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {43}, number = {6}, pages = {e2000331}, pmid = {33914346}, issn = {1521-1878}, support = {R01 CA239120/CA/NCI NIH HHS/United States ; }, mesh = {Black or African American ; COVID-19/*complications/etiology/immunology ; Cytokines/metabolism ; Health Status Disparities ; Humans ; Neoplasms/*etiology/virology ; Race Factors ; }, abstract = {As the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to surge worldwide, our knowledge of coronavirus disease 2019 (COVID-19) is rapidly expanding. Although most COVID-19 patients recover within weeks of symptom onset, some experience lingering symptoms that last for months ("long COVID-19"). Early reports of COVID-19 sequelae, including cardiovascular, pulmonary, and neurological conditions, have raised concerns about the long-term effects of COVID-19, especially in hard-hit communities. It is becoming increasingly evident that cancer patients are more susceptible to SARS-CoV-2 infection and are at a higher risk of severe COVID-19 than the general population. Nevertheless, whether long COVID-19 increases the risk of cancer in those with no prior malignancies, remains unclear. Given, the disproportionate impact of the disease on the African American community, yet another unanswered question is whether racial disparities are to be expected in COVID-19 sequelae. Herein, we propose that long COVID-19 may predispose recovered patients to cancer development and accelerate cancer progression. This hypothesis is based on growing evidence of the ability of SARS-CoV-2 to modulate oncogenic pathways, promote chronic low-grade inflammation, and cause tissue damage. Comprehensive studies are urgently required to elucidate the effects of long COVID-19 on cancer susceptibility.}, } @article {pmid33912905, year = {2022}, author = {Tran, VT and Riveros, C and Clepier, B and Desvarieux, M and Collet, C and Yordanov, Y and Ravaud, P}, title = {Development and Validation of the Long Coronavirus Disease (COVID) Symptom and Impact Tools: A Set of Patient-Reported Instruments Constructed From Patients' Lived Experience.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {74}, number = {2}, pages = {278-287}, doi = {10.1093/cid/ciab352}, pmid = {33912905}, issn = {1537-6591}, mesh = {Adult ; *COVID-19/complications ; Female ; Humans ; Male ; Patient Reported Outcome Measures ; Psychometrics ; Quality of Life ; Reproducibility of Results ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: To develop and validate patient-reported instruments, based on patients' lived experiences, for monitoring the symptoms and impact of long coronavirus disease (covid).

METHODS: The long covid Symptom and Impact Tools (ST and IT) were constructed from the answers to a survey with open-ended questions to 492 patients with long COVID. Validation of the tools involved adult patients with suspected or confirmed coronavirus disease 2019 (COVID-19) and symptoms extending over 3 weeks after onset. Construct validity was assessed by examining the relations of the ST and IT scores with health-related quality of life (EQ-5D-5L), function (PCFS, post-COVID functional scale), and perceived health (MYMOP2, Measure yourself medical outcome profile 2). Reliability was determined by a test-retest. The "patient acceptable symptomatic state" (PASS) was determined by the percentile method.

RESULTS: Validation involved 1022 participants (55% with confirmed COVID-19, 79% female, and 12.5% hospitalized for COVID-19). The long COVID ST and IT scores were strongly correlated with the EQ-5D-5L (rs = -0.45 and rs = -0.59, respectively), the PCFS (rs = -0.39 and rs = -0.55), and the MYMOP2 (rs = -0.40 and rs = -0.59). Reproducibility was excellent with an interclass correlation coefficient of 0.83 (95% confidence interval .80 to .86) for the ST score and 0.84 (.80 to .87) for the IT score. In total, 793 (77.5%) patients reported an unacceptable symptomatic state, thereby setting the PASS for the long covid IT score at 30 (28 to 33).

CONCLUSIONS: The long covid ST and IT tools, constructed from patients' lived experiences, provide the first validated and reliable instruments for monitoring the symptoms and impact of long covid.}, } @article {pmid33911230, year = {2021}, author = {Marx, V}, title = {Scientists set out to connect the dots on long COVID.}, journal = {Nature methods}, volume = {18}, number = {5}, pages = {449-453}, pmid = {33911230}, issn = {1548-7105}, mesh = {Adult ; Aging ; Antibodies, Viral ; Biomedical Research ; COVID-19/*complications/etiology/immunology/*mortality/*pathology ; Female ; Humans ; Male ; RNA, Messenger ; RNA, Viral ; *SARS-CoV-2 ; Sex Factors ; Time Factors ; Viral Proteins ; Post-Acute COVID-19 Syndrome ; }, abstract = {With grit, urgency and creativity, scientists address the puzzle of long-haul COVID.}, } @article {pmid33909072, year = {2021}, author = {Chevinsky, JR and Tao, G and Lavery, AM and Kukielka, EA and Click, ES and Malec, D and Kompaniyets, L and Bruce, BB and Yusuf, H and Goodman, AB and Dixon, MG and Nakao, JH and Datta, SD and MacKenzie, WR and Kadri, SS and Saydah, S and Giovanni, JE and Gundlapalli, AV}, title = {Late Conditions Diagnosed 1-4 Months Following an Initial Coronavirus Disease 2019 (COVID-19) Encounter: A Matched-Cohort Study Using Inpatient and Outpatient Administrative Data-United States, 1 March-30 June 2020.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {Suppl 1}, pages = {S5-S16}, doi = {10.1093/cid/ciab338}, pmid = {33909072}, issn = {1537-6591}, support = {NU50CK000574//Infectious Diseases Society of America through Cooperative Agreement/ ; }, mesh = {Adult ; *COVID-19 ; COVID-19 Testing ; Cohort Studies ; Humans ; Inpatients ; *Outpatients ; SARS-CoV-2 ; United States/epidemiology ; }, abstract = {BACKGROUND: Late sequelae of COVID-19 have been reported; however, few studies have investigated the time course or incidence of late new COVID-19-related health conditions (post-COVID conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed type, association, and timing of post-COVID conditions following COVID-19 diagnosis.

METHODS: Using the Premier Healthcare Database Special COVID-19 Release (release date, 20 October 2020) data, during March-June 2020, 27 589 inpatients and 46 857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted ORs were calculated to assess for late conditions that were more common in case-patients than control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31-120 days following a COVID-19 encounter.

RESULTS: During 31-120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced ≥1 of 5 post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced ≥1 of 10 post-COVID conditions. During 31-60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and also more likely to experience a range of conditions affecting multiple body systems (eg, nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal symptoms) than outpatient control-patients.

CONCLUSIONS: These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform healthcare practice and resource planning for follow-up COVID-19 care.}, } @article {pmid33908722, year = {2021}, author = {Genecand, L and Bridevaux, PO and Garin, N and Thonney, J and Bonvin-Mullor, N and Bouali, R and Frésard, I}, title = {[Diagnostic and therapeutic management of medium and long-term sequelae of SARS-CoV-2 infection].}, journal = {Revue medicale suisse}, volume = {17}, number = {736}, pages = {842-849}, pmid = {33908722}, issn = {1660-9379}, mesh = {*COVID-19 ; Disease Progression ; Humans ; *SARS-CoV-2 ; }, abstract = {Somatic or psychological sequelae after a SARS-CoV-2 infection are common. Specific organ damage should be investigated to explain persistent symptomatology and propose a treatment. A specialized consultation for the follow-up of patients after a SARS-CoV-2 infection is useful to clinically assess the patient, organized further investigations, offer treatment options and refer the patient to other specialists or to a rehabilitation program. Such a consultation is also intended to reduce the public health burden of long Covid and to collect data that can improve our management in the future.}, } @article {pmid33908718, year = {2021}, author = {Benzakour, L and Assal, F and Péron, JA}, title = {[Neuropsychological long-COVID : neurologic or psychiatric origin?].}, journal = {Revue medicale suisse}, volume = {17}, number = {736}, pages = {822-826}, pmid = {33908718}, issn = {1660-9379}, mesh = {*COVID-19 ; Humans ; Hypothalamo-Hypophyseal System ; *Nervous System Diseases ; Pituitary-Adrenal System ; SARS-CoV-2 ; }, abstract = {Among the long-COVID symptoms, neuropsychological sequelae are frequent after an infection by SARS-CoV-2, whatever the severity of the respiratory disease in the acute phase. These deficits seem to result from a neurological disorder, but also from psychiatric symptoms. Not only inflammatory components, which can play a major role in the genesis of the neuropsychological sequelae, but also the hypotheses of vascular systemic lesions, the neurotropism of SARS-CoV-2, or the effect of the stress and the hypothalamic-pituitary-adrenal axis (HPA) are suggested. Psychiatric complications due to SSARS-CoV-2 infection would partly explain these neuropsychological sequelae.}, } @article {pmid33905283, year = {2021}, author = {Chaudhuri, KR and Rukavina, K and McConvey, V and Antonini, A and Lorenzl, S and Bhidayasiri, R and Piemonte, MEP and Lim, SY and Richfield, E and Walker, R and Bouca-Machado, R and Bajwah, S and Gao, W and Trivedi, D and Miyasaki, J}, title = {The impact of COVID-19 on palliative care for people with Parkinson's and response to future pandemics.}, journal = {Expert review of neurotherapeutics}, volume = {21}, number = {6}, pages = {615-623}, doi = {10.1080/14737175.2021.1923480}, pmid = {33905283}, issn = {1744-8360}, mesh = {Aged ; COVID-19/complications/*epidemiology/psychology ; Caregivers/psychology ; Humans ; Minority Groups ; *Palliative Care ; *Pandemics ; Parkinson Disease/ethnology/*therapy ; Quality of Life ; Risk Factors ; SARS-CoV-2 ; Social Support ; Spirituality ; Post-Acute COVID-19 Syndrome ; }, abstract = {Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.}, } @article {pmid33898792, year = {2021}, author = {Kincaid, KJ and Kung, JC and Senetar, AJ and Mendoza, D and Bonnin, DA and Purtlebaugh, WL and Cabatbat, RM and Dickens, R and Echevarria, FD and Kariyawasam, V and Bruzzone, M and Simpkins, AN}, title = {Post-COVID seizure: A new feature of "long-COVID".}, journal = {eNeurologicalSci}, volume = {23}, number = {}, pages = {100340}, pmid = {33898792}, issn = {2405-6502}, abstract = {Novel coronavirus SARS-CoV-2 has created unprecedented healthcare challenges. Neurologic deficits are often an important presenting symptom. To date, the only reported post-infectious COVID-19 manifestations of neurologic disease include cognitive deficits and dysfunction of the peripheral nervous system. Here we report that seizure can also be a post-COVID-19 or "long-COVID" complication. We present a 71-year-old man with hypertension, diabetes mellitus, and COVID-19 diagnosed by RT-PCR who initially presented with posterior circulation stroke-like symptoms, which completely resolved after emergent thrombolysis. Six days later, the patient returned with seizure activity, supported by radiographic and electroencephalographic studies. Notably, he was negative for SARS-CoV-2, and no other provoking factor was uncovered after a comprehensive work-up. To our knowledge, this is the first report of post-infectious seizures after a case of COVID-19, highlighting the potential importance of monitoring for neurologic symptoms in COVID-19 patients, even after convalescence.}, } @article {pmid33896155, year = {2021}, author = {Theoharides, TC and Lauritano, D and Ronconi, G and Calvisi, V and Conti, P}, title = {Antibodies for COVID-19 - which, when and how long?.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {35}, number = {2}, pages = {417-422}, doi = {10.23812/Theo_edit}, pmid = {33896155}, issn = {0393-974X}, mesh = {Antibodies, Viral ; *COVID-19/therapy ; COVID-19 Vaccines ; Humans ; Immunization, Passive ; Peptidyl-Dipeptidase A ; RNA, Viral ; SARS-CoV-2 ; *Spike Glycoprotein, Coronavirus ; COVID-19 Serotherapy ; }, abstract = {Infection with SARS-CoV2 leads to COVID-19, the severity of which derives from the host’s immune response, especially the release of a storm of pro-inflammatory cytokines. This coronavirus infects by first binding to the ectoenzyme Angiotensin Converting Enzyme 2 (ACE2), a serine protease acting as the receptor, while another serine protease is necessary for priming the viral spike “S” protein required for entering the cells. Repurposing existing drugs for potential anti-coronavirus activity have failed. As a result, there were intense efforts to rapidly produce ways of providing prophylactic active immunization (vaccines) or abortive passive (convalescent plasma or monoclonal antibodies) neutralizing antibodies. The availability of vaccines for COVID-19 have been largely successful, but many questions still remain unanswered. In spite of the original enthusiasm, clinical studies using convalescent serum or monoclonal antibodies have shown limited benefit. Moreover, the emergence of Long-COVID syndrome in most infected patients necessitates the development of treatment approaches that may prevent viral entry by blocking both serine proteases involved, as with a liposomal blend of the natural flavonoids luteolin and quercetin.}, } @article {pmid33894903, year = {2021}, author = {Kondratiuk, AL and Pillay, TD and Kon, OM and Lalvani, A}, title = {A conceptual framework to accelerate the clinical impact of evolving research into long COVID.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {6}, pages = {756-757}, pmid = {33894903}, issn = {1474-4457}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Biomedical Research/*statistics & numerical data/*trends ; COVID-19/*complications/epidemiology/*physiopathology ; Forecasting ; Humans ; Long Term Adverse Effects/*physiopathology ; SARS-CoV-2 ; United Kingdom/epidemiology ; }, } @article {pmid33893710, year = {2021}, author = {Sathish, T and Anton, MC and Sivakumar, T}, title = {New-onset diabetes in "long COVID".}, journal = {Journal of diabetes}, volume = {13}, number = {8}, pages = {693-694}, pmid = {33893710}, issn = {1753-0407}, mesh = {Acute Disease ; COVID-19/*complications ; Diabetes Mellitus/*etiology ; Humans ; *SARS-CoV-2 ; }, } @article {pmid33892403, year = {2021}, author = {Raveendran, AV and Jayadevan, R and Sashidharan, S}, title = {Long COVID: An overview.}, journal = {Diabetes & metabolic syndrome}, volume = {15}, number = {3}, pages = {869-875}, pmid = {33892403}, issn = {1878-0334}, mesh = {COVID-19/*complications/epidemiology/etiology/pathology/therapy ; Cough/epidemiology/etiology/therapy ; Fatigue/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND AND AIMS: Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection.

METHODS: WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID.

RESULTS: Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis.

CONCLUSIONS: This review will helps the clinicians to manage various aspects of Long COVID.}, } @article {pmid33890344, year = {2021}, author = {Leta, V and Rodríguez-Violante, M and Abundes, A and Rukavina, K and Teo, JT and Falup-Pecurariu, C and Irincu, L and Rota, S and Bhidayasiri, R and Storch, A and Odin, P and Antonini, A and Ray Chaudhuri, K}, title = {Parkinson's Disease and Post-COVID-19 Syndrome: The Parkinson's Long-COVID Spectrum.}, journal = {Movement disorders : official journal of the Movement Disorder Society}, volume = {36}, number = {6}, pages = {1287-1289}, pmid = {33890344}, issn = {1531-8257}, mesh = {*COVID-19/complications ; Humans ; *Parkinson Disease ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33889231, year = {2021}, author = {Iwu, CJ and Iwu, CD and Wiysonge, CS}, title = {The occurrence of long COVID: a rapid review.}, journal = {The Pan African medical journal}, volume = {38}, number = {}, pages = {65}, pmid = {33889231}, issn = {1937-8688}, mesh = {COVID-19/*complications ; Hospitalization ; Humans ; Randomized Controlled Trials as Topic ; *Survivors ; Time Factors ; }, abstract = {The long-term effects of the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) are not well understood. This rapid review was aimed at synthesizing evidence on the long-term effects of the SARS-CoV-2 infection among survivors. We considered both randomised controlled trials and non-randomised studies eligible for inclusion in this review. The following databases were searched: PubMed, Scopus, Cochrane library, Google Scholar, and the World Health Organization (WHO) COVID-19 database. The reference lists of all the included studies were also searched. Two authors independently screened the search outputs and reviewed full texts of potentially eligible articles. Data extraction was done by one author and checked by a second author. A meta-analysis was not conducted due to heterogeneity among the included studies. Results are presented narratively. Eleven studies met our inclusion criteria. All these studies were conducted in high-income countries. Study findings demonstrate that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness, especially among previously hospitalized persons. The majority of symptoms reported were fatigue, shortness of breath, cough, and sleep disorders. Mental conditions, such as depression and anxiety disorders, were also reported. In conclusion, this study showed that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness. Therefore, there is a need for a long-term follow-up of COVID-19 patients and rehabilitation services for survivors. More research is needed in this area, especially in Africa.}, } @article {pmid33880955, year = {2021}, author = {Parkin, A and Davison, J and Tarrant, R and Ross, D and Halpin, S and Simms, A and Salman, R and Sivan, M}, title = {A Multidisciplinary NHS COVID-19 Service to Manage Post-COVID-19 Syndrome in the Community.}, journal = {Journal of primary care & community health}, volume = {12}, number = {}, pages = {21501327211010994}, pmid = {33880955}, issn = {2150-1327}, mesh = {*COVID-19/complications ; England ; Humans ; SARS-CoV-2 ; State Medicine ; Post-Acute COVID-19 Syndrome ; }, abstract = {The National Institute for Health and Care Excellence (NICE) describe "post COVID-19 syndrome" or "Long COVID" as a set of persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks after illness and which are not explained by an alternative diagnosis. These symptoms are experienced not only by patients discharged from hospital but also those in the community who did not require inpatient care. To support the recovery of this group of people, a unique integrated rehabilitation pathway was developed following extensive service evaluations by Leeds Primary Care Services, Leeds Community Healthcare NHS Trust and Leeds Teaching Hospital NHS Trust. The pathway aligns itself to the NHS England "Five-point plan" to embed post-COVID-19 syndrome assessment clinics across England, supporting the comprehensive medical assessment and rehabilitation intervention for patients in the community. The pathway was first of its kind to be set up in the UK and comprises of a three-tier service model (level 1: specialist MDT service, level 2: community therapy teams and level 3: self-management). The MDT service brings together various disciplines with specialist skill sets to provide targeted individualized interventions using a specific core set of outcome measures including C19-YRS (Yorkshire Rehabilitation Scale). Community and primary care teams worldwide need such an integrated multidisciplinary comprehensive model of care to deal with the growing number of cases of post-COVID-19 syndrome effectively and in a timely manner.}, } @article {pmid33880486, year = {2021}, author = {Mishra, PK and Bruiners, N and Ukey, R and Datta, P and Onyuka, A and Handler, D and Hussain, S and Honnen, W and Singh, S and Guerrini, V and Yin, Y and Dewald, H and Choudhary, A and Horton, DB and Barrett, ES and Roy, J and Weiss, SH and Fitzgerald-Bocarsly, P and Blaser, MJ and Carson, JL and Panettieri, RA and Lardizabal, A and Chang, TL and Pinter, A and Gennaro, ML}, title = {Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {33880486}, support = {U01 AI122285/AI/NIAID NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 AI152157/AI/NIAID NIH HHS/United States ; UL1 TR003017/TR/NCATS NIH HHS/United States ; R01 HL149450/HL/NHLBI NIH HHS/United States ; }, abstract = {Much is to be learned about the interface between immune responses to SARS-CoV-2 infection and vaccination. We monitored immune responses specific to SARS-CoV-2 Spike Receptor-Binding-Domain (RBD) in convalescent individuals for eight months after infection diagnosis and following vaccination. Over time, neutralizing antibody responses, which are predominantly RBD specific, generally decreased, while RBD-specific memory B cells persisted. RBD-specific antibody and B cell responses to vaccination were more vigorous than those elicited by infection in the same subjects or by vaccination in infection-naïve comparators. Notably, the frequencies of double negative B memory cells, which are dysfunctional and potentially pathogenic, increased in the convalescent subjects over time. Unexpectedly, this effect was reversed by vaccination. Our work identifies a novel aspect of immune dysfunction in mild/moderate COVID-19, supports the practice of offering SARS-CoV-2 vaccination regardless of infection history, and provides a potential mechanistic explanation for the vaccination-induced reduction of "Long-COVID" symptoms.}, } @article {pmid33880442, year = {2021}, author = {Wallukat, G and Hohberger, B and Wenzel, K and Fürst, J and Schulze-Rothe, S and Wallukat, A and Hönicke, AS and Müller, J}, title = {Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms.}, journal = {Journal of translational autoimmunity}, volume = {4}, number = {}, pages = {100100}, pmid = {33880442}, issn = {2589-9090}, abstract = {Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved. We, therefore investigated, whether GPCR-fAABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs that acted as receptor agonists. Some of those GPCR-fAABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-fAAB detection). Other GPCR-fAABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-fAABs identified in the blood of Long-COVID patients targeted the β2-adrenoceptor (β2-fAAB), the α1-adrenoceptor (α1-fAAB), the angiotensin II AT1-receptor (AT1-fAAB), and the nociceptin-like opioid receptor (NOC-fAAB). The negative chronotropic GPCR-fAABs identified targeted the muscarinic M2-receptor (M2-fAAB), the MAS-receptor (MAS-fAAB), and the ETA-receptor (ETA-fAAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.}, } @article {pmid33879882, year = {2021}, author = {Mullard, A}, title = {Long COVID's long R&D agenda.}, journal = {Nature reviews. Drug discovery}, volume = {20}, number = {5}, pages = {329-331}, doi = {10.1038/d41573-021-00069-9}, pmid = {33879882}, issn = {1474-1784}, mesh = {COVID-19/*complications/therapy ; Clinical Trials as Topic ; Drug Development ; Hospitalization ; Humans ; Research ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33875855, year = {2021}, author = {Khunti, K and Davies, MJ and Kosiborod, MN and Nauck, MA}, title = {Long COVID - metabolic risk factors and novel therapeutic management.}, journal = {Nature reviews. Endocrinology}, volume = {17}, number = {7}, pages = {379-380}, pmid = {33875855}, issn = {1759-5037}, mesh = {COVID-19/*complications/metabolism/therapy ; *Cardiometabolic Risk Factors ; Cardiovascular Diseases/*complications/therapy ; Diabetes Mellitus, Type 1/complications/therapy ; Diabetes Mellitus, Type 2/complications/therapy ; Humans ; Hypoglycemic Agents/therapeutic use ; Risk Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Cardiometabolic conditions, including type 1 and type 2 diabetes mellitus, are associated with severe COVID-19 and long COVID. Interventions to target multiple risk factors, combined with use of novel glucose-lowering agents that improve metabolic function and the key processes that are impaired in COVID-19, should be the preferred therapeutic options for management of people with long COVID.}, } @article {pmid33875508, year = {2021}, author = {Taribagil, P and Creer, D and Tahir, H}, title = {'Long COVID' syndrome.}, journal = {BMJ case reports}, volume = {14}, number = {4}, pages = {}, pmid = {33875508}, issn = {1757-790X}, mesh = {Adult ; COVID-19/*complications/diagnosis ; Cough/virology ; Dyspnea/virology ; Fatigue/virology ; Female ; Humans ; Memory Disorders/virology ; Myalgia/virology ; Post-Acute COVID-19 Syndrome ; }, abstract = {SARS-CoV-2 has resulted in a global pandemic and an unprecedented public health crisis. Recent literature suggests the emergence of a novel syndrome known as 'long COVID', a term used to describe a diverse set of symptoms that persist after a minimum of 4 weeks from the onset of a diagnosed COVID-19 infection. Common symptoms include persistent breathlessness, fatigue and cough. Other symptoms reported include chest pain, palpitations, neurological and cognitive deficits, rashes, and gastrointestinal dysfunction. We present a complex case of a previously well 28-year-old woman who was diagnosed with COVID-19. After resolution of her acute symptoms, she continued to experience retrosternal discomfort, shortness of breath, poor memory and severe myalgia. Investigations yielded no significant findings. Given no alternative diagnosis, she was diagnosed with 'long COVID'.}, } @article {pmid33867257, year = {2021}, author = {Rodriguez, B and Nansoz, S and Cameron, DR and Z'Graggen, WJ}, title = {Is myopathy part of long-Covid?.}, journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}, volume = {132}, number = {6}, pages = {1241-1242}, pmid = {33867257}, issn = {1872-8952}, mesh = {Adult ; COVID-19/*complications ; Female ; Humans ; Muscular Diseases/*etiology ; }, } @article {pmid33861695, year = {2021}, author = {Mertz, L}, title = {Researchers Seek Answers for Millions With Long COVID-19.}, journal = {IEEE pulse}, volume = {12}, number = {2}, pages = {17-21}, doi = {10.1109/MPULS.2021.3066718}, pmid = {33861695}, issn = {2154-2317}, mesh = {Adult ; Autoimmunity ; COVID-19/*complications/epidemiology/etiology/physiopathology/rehabilitation ; Cognitive Dysfunction/etiology ; Cohort Studies ; Fatigue/etiology ; Female ; Host Microbial Interactions/immunology/physiology ; Humans ; Male ; New York City/epidemiology ; *Pandemics ; Primary Dysautonomias/etiology ; *SARS-CoV-2 ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {"I am now eight-and-a-half months into my journey with long COVID … My symptoms include diagnosed post-COVID tachycardia and acute fatigue. I also have chest tightness and breathlessness from time to time; anxiety; muscle aches and pains, especially in the evening; memory loss; and insomnia."-38-year-old female from the U.K.}, } @article {pmid33861398, year = {2021}, author = {Funk, GC and Nell, C and Pokieser, W and Thaler, B and Rainer, G and Valipour, A}, title = {Organizing pneumonia following Covid19 pneumonia.}, journal = {Wiener klinische Wochenschrift}, volume = {133}, number = {17-18}, pages = {979-982}, pmid = {33861398}, issn = {1613-7671}, mesh = {*COVID-19 ; Humans ; Lung ; *Pneumonia/diagnosis/drug therapy ; SARS-CoV-2 ; }, abstract = {The potential mid-term and long-term consequences after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are as yet unknown. This is the first report of bronchoscopically verified organizing pneumonia as a complication of coronavirus disease 2019 (Covid19). It caused persisting dyspnea, impaired pulmonary function, and radiological abnormalities over 5 weeks after onset of symptoms. While organizing pneumonia frequently requires treatment with systemic corticosteroids, in this case it resolved spontaneously without treatment after 6 weeks. Healthcare professionals should consider organizing pneumonia in patients with persisting respiratory symptoms after Covid19.}, } @article {pmid33860736, year = {2021}, author = {Southwick, L and Guntuku, SC and Klinger, EV and Pelullo, A and McCalpin, H and Merchant, RM}, title = {The role of digital health technologies in COVID-19 surveillance and recovery: a specific case of long haulers.}, journal = {International review of psychiatry (Abingdon, England)}, volume = {33}, number = {4}, pages = {412-423}, doi = {10.1080/09540261.2020.1854195}, pmid = {33860736}, issn = {1369-1627}, mesh = {COVID-19/*therapy ; Humans ; Physical Distancing ; *Public Health Surveillance ; *Recovery of Function ; *Social Media ; Telemedicine/*trends ; Time Factors ; Wearable Electronic Devices/*supply & distribution ; }, abstract = {Digital health and technologies are essential to curbing the novel coronavirus 2019 (COVID-19) pandemic especially with shelter-in-place and social distancing orders. Epidemiologists and public health officials are tapping into frequently used technologies like wearables, digital devices, digital and social media data to detect and validate COVID-19 symptoms throughout the pandemic, especially during early stages when symptoms were evolving. In this article, we review how digital technologies and social media platforms can identify and inform our understanding of COVID-19 pandemic surveillance and recovery efforts. We analyze Reddit narrative posts and comments on r/covidlonghaulers to demonstrate how social media can be used to better understand COVID-19 pandemic. Using Reddit data, we highlight long haulers' patient journeys and shed light on potential consequences of their condition. We identified 21 themes, of which the following were significantly associated with valence: COVID-19 Symptoms (r = -0.037), medical advice (r = -0.030), medical system (r = -0.029), bodily processes (r = -0.020), questions (r = 0.024), physical activity (r = 0.033), self-differentials and negations (r = 0.040) and supplements (r = 0.025). Our brief literature review and analysis of r/covidlonghaulers narrative posts demonstrate the value of digital technologies and social media platforms as they act as modern avenues for public health, safety, and well-being.}, } @article {pmid33857435, year = {2021}, author = {Song, WJ and Hui, CKM and Hull, JH and Birring, SS and McGarvey, L and Mazzone, SB and Chung, KF}, title = {Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {5}, pages = {533-544}, pmid = {33857435}, issn = {2213-2619}, mesh = {COVID-19/*complications/*physiopathology ; Cough/*etiology/physiopathology ; Humans ; Inflammation/*etiology/physiopathology ; Nervous System Diseases/*etiology/physiopathology ; *Neuroimmunomodulation ; SARS-CoV-2 ; Syndrome ; }, abstract = {Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.}, } @article {pmid33852979, year = {2021}, author = {Molero-García, JM and Arranz-Izquierdo, J and Gutiérrez-Pérez, MI and Redondo Sánchez, JM}, title = {[Basic aspects of COVID-19 for management from primary care].}, journal = {Atencion primaria}, volume = {53}, number = {6}, pages = {101966}, pmid = {33852979}, issn = {1578-1275}, mesh = {Aftercare/methods ; Asymptomatic Diseases ; COVID-19/*diagnosis/epidemiology/*therapy/transmission ; COVID-19 Testing/methods ; Combined Modality Therapy ; Humans ; Primary Health Care/*methods ; Severity of Illness Index ; Spain/epidemiology ; }, abstract = {SARS-CoV-2 is transmitted from person to person by inhalation or contact with respiratory droplets and aerosols. The median incubation period is 5.1 days. Fever, dry cough, dyspnea and fatigue are the most common symptoms. Almost half of the cases are asymptomatic. The spectrum of disease varies from mild (81%) to critical (5%). Older age, male gender and comorbidities negatively impact on the severity and mortality of COVID-19. The diagnosis of acute COVID-19 is made with RT-PCR or antigenic detection tests. In hospital patients, remdesivir reduces recovery time. Oral steroids are recommended for severe or critical cases requiring oxygen therapy or mechanical ventilation. Thromboprophylaxis is recommended in all severe and non-severe cases with high thrombotic risk. Antibiotherapy is limited to cases of high suspicion of bacterial superinfection. Mild-moderate and severe cases after discharge from hospital should be clinically monitored for a minimum period of two weeks.}, } @article {pmid33850105, year = {2021}, author = {Ortona, E and Buonsenso, D and Carfi, A and Malorni, W and , }, title = {Long COVID: an estrogen-associated autoimmune disease?.}, journal = {Cell death discovery}, volume = {7}, number = {1}, pages = {77}, pmid = {33850105}, issn = {2058-7716}, support = {COVID-2020-12371817//Ministero della Salute (Ministry of Health, Italy)/ ; }, } @article {pmid33847020, year = {2021}, author = {Theoharides, TC and Cholevas, C and Polyzoidis, K and Politis, A}, title = {Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue.}, journal = {BioFactors (Oxford, England)}, volume = {47}, number = {2}, pages = {232-241}, pmid = {33847020}, issn = {1872-8081}, mesh = {Brain/drug effects/physiopathology/virology ; COVID-19/complications/physiopathology/virology ; Cognitive Dysfunction/complications/*drug therapy/physiopathology/virology ; Cytokines/genetics ; Fatigue/complications/*drug therapy/physiopathology/virology ; Humans ; Luteolin/*therapeutic use ; Mast Cells/drug effects/virology ; SARS-CoV-2/pathogenicity ; *COVID-19 Drug Treatment ; }, abstract = {COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.}, } @article {pmid33842517, year = {2021}, author = {Lidbury, BA}, title = {Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {662513}, pmid = {33842517}, issn = {2296-858X}, abstract = {Ross River virus (RRV) is an endemic Australian arbovirus, and member of the Alphavirus family that also includes Chikungunya virus (CHIK). RRV is responsible for the highest prevalence of human disease cases associated with mosquito-borne transmission in Australia, and has long been a leading suspect in cases of post-viral fatigue syndromes, with extrapolation of this link to Myalgic Encephalomyelitis (ME). Research into RRV pathogenesis has revealed a number of immune evasion strategies, impressive for a virus with a genome size of 12 kb (plus strand RNA), which resonate with insights into viral pathogenesis broadly. Drawing from observations on RRV immune evasion, mechanisms of relevance to long term idiopathic fatigue are featured as a perspective on infection and eventual ME symptoms, which include considerations of; (1) selective pro-inflammatory gene suppression post antibody-dependent enhancement (ADE) of RRV infection, (2) Evidence from other virus families of immune disruption and evasion post-ADE, and (3) how virally-driven immune evasion may impact on mitochondrial function via target of rapamycin (TOR) complexes. In light of these RRV measures to counter the host immune - inflammatory responses, links to recent discoveries explaining cellular, immune and metabolomic markers of ME will be explored and discussed, with the implications for long-COVID post SARS-CoV-2 also considered. Compelling issues on the connections between virally-induced alterations in cytokine expression, for example, will be of particular interest in light of energy pathways, and how these perturbations manifest clinically.}, } @article {pmid33839588, year = {2021}, author = {Froidure, A and Mahsouli, A and Liistro, G and De Greef, J and Belkhir, L and Gérard, L and Bertrand, A and Koenig, S and Pothen, L and Yildiz, H and Mwenge, B and Aboubakar, F and Gohy, S and Pilette, C and Reychler, G and Coche, E and Yombi, JC and Ghaye, B}, title = {Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae.}, journal = {Respiratory medicine}, volume = {181}, number = {}, pages = {106383}, pmid = {33839588}, issn = {1532-3064}, mesh = {Aged ; COVID-19/complications/*diagnostic imaging/*physiopathology ; Cohort Studies ; Dyspnea/etiology ; Fatigue/etiology ; Female ; Follow-Up Studies ; Humans ; Linear Models ; Lung/*diagnostic imaging/*physiopathology ; Male ; Middle Aged ; Positron-Emission Tomography ; Radiographic Image Enhancement ; Respiratory Function Tests ; Severity of Illness Index ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: COVID-19 pandemic resulted in an unprecedented number of hospitalizations in general wards and intensive care units (ICU). Severe and critical COVID-19 patients suffer from extensive pneumonia; therefore, long-term respiratory sequelae may be expected.

RESEARCH QUESTION: We conducted a cohort study to determine respiratory sequelae in patients with severe and critical COVID-19. We aimed at evaluating the proportion of patients with persisting respiratory symptoms and/or abnormalities in pulmonary function tests (PFT) or in lung imaging.

STUDY DESIGN: and methods: This is a single center cohort study including COVID-19 survivors who underwent a three-month follow-up with clinical evaluation, PFT and lung high-resolution computed tomography (HRCT). All clinical, functional, and radiological data were centrally reviewed. Multiple linear regression analysis was performed to identify factors associated with residual lesions on HRCT.

RESULTS: Full clinical evaluation, PFT and lung HRCT were available for central review in 126, 122 and 107 patients, respectively. At follow-up, 25% of patients complained from dyspnea and 35% from fatigue, lung diffusion capacity (DLCO) was decreased in 45%, 17% had HRCT abnormalities affecting more than 5% of their lung parenchyma while signs of fibrosis were found in 21%. In multiple linear regression model, number of days in ICU were related to the extent of persisting lesions on HRCT, while intubation was associated with signs of fibrosis at follow-up (P = 0.0005, Fisher's exact test). In contrast, the severity of lung imaging or PFT changes were not predictive of fatigue and dyspnea.

INTERPRETATION: Although most hospitalized COVID-19 patients recover, a substantial proportion complains from persisting dyspnea and fatigue. Impairment of DLCO and signs suggestive of fibrosis are common but are not strictly related to long-lasting symptoms.}, } @article {pmid33835507, year = {2021}, author = {Buonsenso, D and Munblit, D and De Rose, C and Sinatti, D and Ricchiuto, A and Carfi, A and Valentini, P}, title = {Preliminary evidence on long COVID in children.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {7}, pages = {2208-2211}, pmid = {33835507}, issn = {1651-2227}, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33834881, year = {2021}, author = {Chmiel, C}, title = {[Not Available].}, journal = {Praxis}, volume = {110}, number = {7}, pages = {403-404}, doi = {10.1024/1661-8157/a003679}, pmid = {33834881}, issn = {1661-8157}, mesh = {*COVID-19 ; Disease Progression ; Humans ; *SARS-CoV-2 ; }, } @article {pmid33834529, year = {2021}, author = {Ludvigsson, JF}, title = {Spanish telemedicine data on 8 children support concept of 'long covid' in children.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {7}, pages = {2284}, pmid = {33834529}, issn = {1651-2227}, mesh = {*COVID-19/complications ; Child ; Humans ; SARS-CoV-2 ; *Telemedicine ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33830208, year = {2021}, author = {Gaber, TAK and Ashish, A and Unsworth, A}, title = {Persistent post-covid symptoms in healthcare workers.}, journal = {Occupational medicine (Oxford, England)}, volume = {71}, number = {3}, pages = {144-146}, pmid = {33830208}, issn = {1471-8405}, mesh = {COVID-19/*complications ; *Fatigue ; Health Personnel/*psychology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Recent reports suggest a higher incidence of COVID-19 infections among healthcare workers (HCW). However, information about the long-term complications affecting this population is lacking.

AIMS: Investigation of long-term impact of COVID-19 in HCW.

METHODS: Seropositivity for SARS-CoV-2 antibodies was evaluated for the majority of HCW in an English teaching hospital 2 months following the peak of COVID-19 first wave. A questionnaire investigating the long-term complications was sent through global e-mail to HCW 4 months following the peak of the wave enquiring about the persistent health issues still affecting them at that point.

RESULTS: Out of 3759 subjects tested for SARS-CoV-2 antibodies, 932 were positive (24%). Forty-five per cent of 138 HCW responding to the questionnaire reported persistent symptoms with 32% struggling to cope 3-4 months following the peak of the wave. Moderate-to-severe fatigue stood out as the most disabling symptom (39%) but mild-to-moderate shortness of breath, anxiety and sleep disturbance were almost universal in the subjects still struggling with symptoms. Only 16% consulted their general practitioner (GP) about their symptoms with only 2% taking sick leave after recovering from the acute illness.

CONCLUSIONS: Our data suggest that about a third of HCW who responded to the survey were still struggling to cope with the symptoms of what is now known as long covid several months after the acute COVID-19 infections. The overwhelming majority of this group seem to be reluctant to neither seek medical advice nor take sick leave.}, } @article {pmid33823752, year = {2021}, author = {Otte, MS and Bork, ML and Zimmermann, PH and Klussmann, JP and Luers, JC}, title = {Persisting olfactory dysfunction improves in patients 6 months after COVID-19 disease.}, journal = {Acta oto-laryngologica}, volume = {141}, number = {6}, pages = {626-629}, doi = {10.1080/00016489.2021.1905178}, pmid = {33823752}, issn = {1651-2251}, mesh = {Ageusia/virology ; COVID-19/*complications ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Olfaction Disorders/*virology ; *Recovery of Function ; *Sensory Thresholds ; }, abstract = {BACKGROUND: Smell disorders persist in about half of the patients with other symptoms of COVID-19 disease, but the exact duration of the symptoms is yet unknown. Especially, only a few studies used validated olfactory tests for this.

AIMS/OBJECTIVES: The aim of this study was to investigate how many patients with olfactory function impairment, which was detected in a validated olfactory test 3 months after COVID-19 disease, showed improvement in olfactory function after 6 months.

METHODS: About 26 patients with a PCR-confirmed, former COVID-19 disease, with an impaired olfactory function after three months, were included in the study. The olfactory function was evaluated with the sniffing sticks test, the taste function with taste sprays.

RESULTS: Smelling function improved in all but one patient (96%). All measured subitems, i.e. olfactory threshold, identification and discrimination of odours significantly improved. In the whole mouth taste test all patients showed normal taste function.

CONCLUSIONS AND SIGNIFICANCE: 6 months after COVID-19 disease, olfactory function improves in just about all patients. Long-term measurements must investigate whether complete regeneration of the olfactory function will occur in all patients.}, } @article {pmid33823427, year = {2021}, author = {Miskowiak, KW and Johnsen, S and Sattler, SM and Nielsen, S and Kunalan, K and Rungby, J and Lapperre, T and Porsberg, CM}, title = {Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables.}, journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, volume = {46}, number = {}, pages = {39-48}, pmid = {33823427}, issn = {1873-7862}, mesh = {Aged ; COVID-19/*epidemiology/*psychology ; Cognitive Dysfunction/*epidemiology/*psychology ; Denmark/epidemiology ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Patient Discharge/*trends ; Prospective Studies ; *Severity of Illness Index ; Time Factors ; }, abstract = {The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3-4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59% to 65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.}, } @article {pmid33822179, year = {2021}, author = {Rayner, C and Campbell, R}, title = {Long Covid Implications for the workplace.}, journal = {Occupational medicine (Oxford, England)}, volume = {71}, number = {3}, pages = {121-123}, doi = {10.1093/occmed/kqab042}, pmid = {33822179}, issn = {1471-8405}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; *Workplace ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33821250, year = {2021}, author = {Shuwa, HA and Shaw, TN and Knight, SB and Wemyss, K and McClure, FA and Pearmain, L and Prise, I and Jagger, C and Morgan, DJ and Khan, S and Brand, O and Mann, ER and Ustianowski, A and Bakerly, ND and Dark, P and Brightling, CE and Brij, S and , and Felton, T and Simpson, A and Grainger, JR and Hussell, T and Konkel, JE and Menon, M}, title = {Alterations in T and B cell function persist in convalescent COVID-19 patients.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {6}, pages = {720-735.e4}, pmid = {33821250}, issn = {2666-6340}, support = {/WT_/Wellcome Trust/United Kingdom ; 21927/VAC_/Versus Arthritis/United Kingdom ; MR/L011840/1/MRC_/Medical Research Council/United Kingdom ; MR/V028448/1/MRC_/Medical Research Council/United Kingdom ; BB/M025977/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/S01103X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 202865/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {CD8-Positive T-Lymphocytes ; *COVID-19 ; Cytokines ; Humans ; Interleukin-10 ; Interleukin-6 ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined.

METHODS: Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3-6 months of convalescence.

FINDINGS: We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8[+] T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6[+] B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10[+] B cells was associated with the resolution of lung pathology.

CONCLUSIONS: Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.

FUNDING: Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving.}, } @article {pmid33817685, year = {2021}, author = {Sancak, B and Ozer Agirbas, U and Kilic, C}, title = {Long COVID and Its Psychiatric Aspects.}, journal = {Journal of the Academy of Consultation-Liaison Psychiatry}, volume = {62}, number = {4}, pages = {480-481}, pmid = {33817685}, issn = {2667-2960}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33813593, year = {2021}, author = {Fontana, IC and Souza, DG and Pellerin, L and Souza, DO and Zimmer, ER}, title = {About the source and consequences of [18]F-FDG brain PET hypometabolism in short and long COVID-19.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {48}, number = {9}, pages = {2674-2675}, pmid = {33813593}, issn = {1619-7089}, support = {88887.185806/2018-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 88887.507218/2020-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 88887.507161/2020-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 465671/2014-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 440763/2016-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 435642/2018-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 312410/2018-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 152189/2020-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 16/2551-0000475-7//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; 19/2551-0000700-0//Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul/ ; Serra-1912-31365//Instituto Serrapilheira/ ; }, mesh = {Brain/diagnostic imaging ; *COVID-19/complications ; *Fluorodeoxyglucose F18 ; Humans ; Positron-Emission Tomography ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33811910, year = {2021}, author = {Santhosh, L and Block, B and Kim, SY and Raju, S and Shah, RJ and Thakur, N and Brigham, EP and Parker, AM}, title = {Rapid Design and Implementation of Post-COVID-19 Clinics.}, journal = {Chest}, volume = {160}, number = {2}, pages = {671-677}, pmid = {33811910}, issn = {1931-3543}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; }, mesh = {Aftercare/*organization & administration ; *COVID-19/therapy ; Hospital Design and Construction ; Humans ; Outpatient Clinics, Hospital/*organization & administration ; *Survivors ; Time Factors ; }, abstract = {Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.}, } @article {pmid33807869, year = {2021}, author = {Fernández-de-Las-Peñas, C and Palacios-Ceña, D and Gómez-Mayordomo, V and Cuadrado, ML and Florencio, LL}, title = {Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {5}, pages = {}, pmid = {33807869}, issn = {1660-4601}, mesh = {*COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {The pandemic of the coronavirus disease 2019 (COVID-19) has provoked a second pandemic, the "long-haulers", i.e., individuals presenting with post-COVID symptoms. We propose that to determine the presence of post-COVID symptoms, symptoms should appear after the diagnosis of SARS-CoV-2 infection; however, this situation has some problems due to the fact that not all people infected by SARS-CoV-2 receive such diagnosis. Based on relapsing/remitting nature of post-COVID symptoms, the following integrative classification is proposed: potentially infection related-symptoms (up to 4-5 weeks), acute post-COVID symptoms (from week 5 to week 12), long post-COVID symptoms (from week 12 to week 24), and persistent post-COVID symptoms (lasting more than 24 weeks). The most important topic is to establish the time reference points. The classification also integrates predisposing intrinsic and extrinsic factors and hospitalization data which could promote post-COVID symptoms. The plethora of symptoms affecting multiple systems exhibited by "long-haulers" suggests the presence of different underlying mechanisms.}, } @article {pmid33807280, year = {2021}, author = {Vollbracht, C and Kraft, K}, title = {Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue.}, journal = {Nutrients}, volume = {13}, number = {4}, pages = {}, pmid = {33807280}, issn = {2072-6643}, mesh = {Ascorbic Acid/administration & dosage/*therapeutic use ; COVID-19/*complications/pathology ; Fatigue/*drug therapy/*etiology ; Feasibility Studies ; Humans ; Injections, Intravenous ; *SARS-CoV-2 ; }, abstract = {Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.}, } @article {pmid33796241, year = {2021}, author = {Wildwing, T and Holt, N}, title = {The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services.}, journal = {Therapeutic advances in chronic disease}, volume = {12}, number = {}, pages = {2040622320976979}, pmid = {33796241}, issn = {2040-6223}, abstract = {AIMS: In response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called 'Long Covid' on neurological services and primary care and similarities with other neurological disorders are discussed.

METHODS: Firstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly, the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders. A total of 45 systematic reviews were identified within seven databases, published between 11 April 2020 and 15 October 2020, following a search in June 2020, updated on 20 October 2020.

RESULTS: The results indicated that COVID-19 exhibits two types of neurological symptoms; life-threatening symptoms such as Guillain-Barre Syndrome (GBS) and encephalitis, and less devastating symptoms such as fatigue and myalgia. Many of these so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome (CFS) and functional neurological disorder (FND).

CONCLUSION: Implications for neurological healthcare services in the United Kingdom (UK) may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals' perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals' perceptions of neurological symptoms because of COVID-19.}, } @article {pmid33795319, year = {2021}, author = {Naidu, SB and Shah, AJ and Saigal, A and Smith, C and Brill, SE and Goldring, J and Hurst, JR and Jarvis, H and Lipman, M and Mandal, S}, title = {The high mental health burden of "Long COVID" and its association with on-going physical and respiratory symptoms in all adults discharged from hospital.}, journal = {The European respiratory journal}, volume = {57}, number = {6}, pages = {}, pmid = {33795319}, issn = {1399-3003}, mesh = {Adult ; *COVID-19 ; Hospitals ; Humans ; *Mental Health ; Patient Discharge ; SARS-CoV-2 ; }, abstract = {Adults discharged from hospital with COVID-19 may experience “Long COVID”, where mental health symptoms are significant and linked to physical symptoms such as breathlessness. Clinicians should use brief screening questionnaires to support their recovery. https://bit.ly/3d22SJM}, } @article {pmid33795224, year = {2021}, author = {Sivan, M and Rayner, C and Delaney, B}, title = {Fresh evidence of the scale and scope of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {373}, number = {}, pages = {n853}, doi = {10.1136/bmj.n853}, pmid = {33795224}, issn = {1756-1833}, mesh = {*COVID-19 ; Hospitalization ; Hospitals ; Humans ; Retrospective Studies ; SARS-CoV-2 ; }, } @article {pmid33791733, year = {2021}, author = {Rando, HM and Bennett, TD and Byrd, JB and Bramante, C and Callahan, TJ and Chute, CG and Davis, HE and Deer, R and Gagnier, J and Koraishy, FM and Liu, F and McMurry, JA and Moffitt, RA and Pfaff, ER and Reese, JT and Relevo, R and Robinson, PN and Saltz, JH and Solomonides, A and Sule, A and Topaloglu, U and Haendel, MA}, title = {Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {33791733}, support = {UL1 TR003096/TR/NCATS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; UL1 TR001998/TR/NCATS NIH HHS/United States ; UL1 TR002537/TR/NCATS NIH HHS/United States ; P30 DK092926/DK/NIDDK NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR002736/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; UL1 TR003107/TR/NCATS NIH HHS/United States ; UL1 TR003015/TR/NCATS NIH HHS/United States ; UL1 TR002733/TR/NCATS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; UL1 TR000460/TR/NCATS NIH HHS/United States ; U24 TR002306/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; R01 LM008111/LM/NLM NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; UL1 TR002553/TR/NCATS NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; R01 HG010067/HG/NHGRI NIH HHS/United States ; P30 AG024832/AG/NIA NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; K23 HL128909/HL/NHLBI NIH HHS/United States ; UL1 TR002544/TR/NCATS NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; }, abstract = {Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely "Long COVID", but also "COVID-19 syndrome (PACS)" or, "post-acute sequelae of SARS-CoV-2 infection (PASC)". In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.}, } @article {pmid33787016, year = {2021}, author = {Prieto, MA and Prieto, O and Castro, HM}, title = {[Long covid: cross sectional study].}, journal = {Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina)}, volume = {78}, number = {1}, pages = {33-36}, pmid = {33787016}, issn = {1853-0605}, mesh = {*COVID-19 ; Cross-Sectional Studies ; Humans ; Retrospective Studies ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a public health problem worldwide. After 3 weeks of the onset of the disease, between 10-87% of patients persist with symptoms. The objective of the study was to evaluate the persistence of symptoms in patients with COVID-19, the associated factors, and to explore the patients' perception of the disease.

MATERIALS AND METHODS: We conducted a cross-sectional study that included 85 patients with a confirmed diagnosis of COVID-19, who attended on an outpatient basis after the acute phase (> 3 weeks) of the disease.

RESULTS: The median time from diagnosis to outpatient consultation was 53 days (interquartile range 31-65). Most (86%) had mild disease, 45% were women and the mean age was 43 years (standard deviation of 13). After the acute phase of the disease 52% (95% CI 41-63%) of the patients persisted with symptoms. The most frequently persistent symptoms were fatigue (49%) and cough (33%). Nineteen percent had insomnia and sixteen percent had anxiety. Female sex, obesity, age between 35-55 years, and initial hospitalization were associated with the persistence of symptoms. Twenty percent of the patients stopped following the prevention recommendations because they believed they were immunized.

CONCLUSION: More than half of the patients persisted with symptoms 3 weeks after the COVID-19 diagnosis, so medical follow-up is important. Female sex, obesity, age 35-55 years, and initial hospitalization were associated factors. The symptoms usually resolved over time.}, } @article {pmid33786465, year = {2021}, author = {Alwan, NA and Johnson, L}, title = {Defining long COVID: Going back to the start.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {5}, pages = {501-504}, pmid = {33786465}, issn = {2666-6340}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {"Long COVID" is the condition whereby affected individuals do not recover for several weeks or months following the onset of symptoms suggestive of COVID-19, whether tested or not.[1] The name "long COVID" was created by the people experiencing it in Spring 2020 to describe their journeys of not recovering.[2] Here, we suggest a way to standardize its definition through outlining what constitutes initial infection with COVID-19.}, } @article {pmid33785926, year = {2021}, author = {Graham, F}, title = {Daily briefing: What the science says about long COVID.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-021-00856-9}, pmid = {33785926}, issn = {1476-4687}, } @article {pmid33785495, year = {2021}, author = {Dennis, A and Wamil, M and Alberts, J and Oben, J and Cuthbertson, DJ and Wootton, D and Crooks, M and Gabbay, M and Brady, M and Hishmeh, L and Attree, E and Heightman, M and Banerjee, R and Banerjee, A and , }, title = {Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study.}, journal = {BMJ open}, volume = {11}, number = {3}, pages = {e048391}, pmid = {33785495}, issn = {2044-6055}, mesh = {Activities of Daily Living ; Adult ; Aged ; COVID-19/*complications/epidemiology/physiopathology ; Case-Control Studies ; Community-Based Participatory Research ; Diabetes Mellitus, Type 2/complications ; Female ; Hospitalization/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVE: To assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection.

DESIGN: Baseline findings from a prospective, observational cohort study.

SETTING: Community-based individuals from two UK centres between 1 April and 14 September 2020.

PARTICIPANTS: Individuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls.

INTERVENTION: Assessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI.

MAIN OUTCOME MEASURES: Severe post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation.

RESULTS: 201 individuals (mean age 45, range 21-71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110-162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05).

CONCLUSIONS: In individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities.

TRIAL REGISTRATION NUMBER: NCT04369807; Pre-results.}, } @article {pmid33785027, year = {2021}, author = {Carson, G and , }, title = {Research priorities for Long Covid: refined through an international multi-stakeholder forum.}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {84}, pmid = {33785027}, issn = {1741-7015}, support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_19026/MRC_/Medical Research Council/United Kingdom ; MC_UU_12014/8/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications ; Consensus Development Conferences as Topic ; Humans ; International Cooperation ; Research ; *SARS-CoV-2 ; Stakeholder Participation ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33784738, year = {2021}, author = {Meagher, T}, title = {Long COVID - An Early Perspective.}, journal = {Journal of insurance medicine (New York, N.Y.)}, volume = {49}, number = {1}, pages = {19-23}, doi = {10.17849/insm-49-1-1-5.1}, pmid = {33784738}, issn = {0743-6661}, mesh = {COVID-19/*economics/*physiopathology ; Humans ; Insurance Carriers ; Insurance, Life ; Risk Assessment ; SARS-CoV-2 ; *Survivors ; Syndrome ; }, abstract = {A new syndrome called "Long COVID" has emerged amongst the survivors of acute COVID-19 infection. Its protracted and debilitating nature will almost certainly result in many short and long-term disability claims. Insurers need to understand the nature of Long COVID, including its definition, its prevalence, its natural history, and underlying risk factors. This article will summarize current knowledge of Long COVID and provide a perspective on its evolution and its impact.}, } @article {pmid33783907, year = {2021}, author = {Berger, Z and Altiery DE Jesus, V and Assoumou, SA and Greenhalgh, T}, title = {Long COVID and Health Inequities: The Role of Primary Care.}, journal = {The Milbank quarterly}, volume = {99}, number = {2}, pages = {519-541}, pmid = {33783907}, issn = {1468-0009}, mesh = {COVID-19/*complications/economics/epidemiology/physiopathology ; Health Care Costs/statistics & numerical data ; *Health Status Disparities ; Humans ; Poverty ; Primary Health Care/*organization & administration ; Racism ; *Social Determinants of Health ; United States/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {Policy Points An estimated 700,000 people in the United States have "long COVID," that is, symptoms of COVID-19 persisting beyond three weeks. COVID-19 and its long-term sequelae are strongly influenced by social determinants such as poverty and by structural inequalities such as racism and discrimination. Primary care providers are in a unique position to provide and coordinate care for vulnerable patients with long COVID. Policy measures should include strengthening primary care, optimizing data quality, and addressing the multiple nested domains of inequity.}, } @article {pmid33769552, year = {2022}, author = {Cinar, R and Iyer, MR and Kunos, G}, title = {Dual inhibition of CB1 receptors and iNOS, as a potential novel approach to the pharmacological management of acute and long COVID-19.}, journal = {British journal of pharmacology}, volume = {179}, number = {10}, pages = {2121-2127}, pmid = {33769552}, issn = {1476-5381}, mesh = {*COVID-19/complications ; Endocannabinoids ; Humans ; Lung ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; }, abstract = {COVID-19 (SARS-CoV-2) causes multiple inflammatory complications, resulting not only in severe lung inflammation but also harm to other organs. Although the current focus is on the management of acute COVID-19, there is growing concern about long-term effects of COVID-19 (Long Covid), such as fibroproliferative changes in the lung, heart and kidney. Therefore, the identification of therapeutic targets not only for the management of acute COVID-19 but also for preventing Long Covid are needed, and would mitigate against long-lasting health burden and economic costs, in addition to saving lives. COVID-19 induces pathological changes via multiple pathways, which could be targeted simultaneously for optimal effect. We discuss the potential pathologic function of increased activity of the endocannabinoid/CB1 receptor system and inducible NO synthase (iNOS). We advocate a polypharmacology approach, wherein a single chemical entity simultaneously interacts with CB1 receptors and iNOS causing inhibition, as a potential therapeutic strategy for COVID-19-related health complications. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.}, } @article {pmid33765941, year = {2021}, author = {Osikomaiya, B and Erinoso, O and Wright, KO and Odusola, AO and Thomas, B and Adeyemi, O and Bowale, A and Adejumo, O and Falana, A and Abdus-Salam, I and Ogboye, O and Osibogun, A and Abayomi, A}, title = {'Long COVID': persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {304}, pmid = {33765941}, issn = {1471-2334}, support = {NA//Lagos State Government/ ; }, mesh = {Adult ; COVID-19/*complications ; Chest Pain/virology ; Comorbidity ; Fatigue/virology ; Female ; Headache/virology ; Humans ; Male ; Middle Aged ; Nigeria/epidemiology ; Patient Discharge ; Quality of Life ; Retrospective Studies ; *Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Coronavirus disease once thought to be a respiratory infection is now recognised as a multi-system disease affecting the respiratory, cardiovascular, gastrointestinal, neurological, immune, and hematopoietic systems. An emerging body of evidence suggests the persistence of COVID-19 symptoms of varying patterns among some survivors. This study aimed to describe persistent symptoms in COVID-19 survivors and investigate possible risk factors for these persistent symptoms.

METHODS: The study used a retrospective study design. The study population comprised of discharged COVID-19 patients. Demographic information, days since discharge, comorbidities, and persistent COVID-19 like symptoms were assessed in patients attending the COVID-19 outpatient clinic in Lagos State. Statistical analysis was done using STATA 15.0 software (StataCorp Texas) with significance placed at p-value < 0.05.

RESULTS: A total of 274 patients were enrolled in the study. A majority were within the age group > 35 to ≤49 years (38.3%), and male (66.1%). More than one-third (40.9%) had persistent COVID-19 symptoms after discharge, and 19.7% had more than three persistent COVID-like symptoms. The most persistent COVID-like symptoms experienced were easy fatigability (12.8%), headaches (12.8%), and chest pain (9.8%). Symptomatic COVID-19 disease with moderate severity compared to mild severity was a predictor of persistent COVID-like symptoms after discharge (p < 0.05).

CONCLUSION: Findings from this study suggests that patients who recovered from COVID-19 disease may still experience COVID-19 like symptoms, particularly fatigue and headaches. Therefore, careful monitoring should be in place after discharge to help mitigate the effects of these symptoms and improve the quality of life of COVID-19 survivors.}, } @article {pmid33764478, year = {2021}, author = {Lemhöfer, C and Gutenbrunner, C and Schiller, J and Loudovici-Krug, D and Best, N and Bökel, A and Sturm, C}, title = {Assessment of rehabilitation needs in patients after COVID-19: Development of the COVID-19-rehabilitation needs survey.}, journal = {Journal of rehabilitation medicine}, volume = {53}, number = {4}, pages = {jrm00183}, pmid = {33764478}, issn = {1651-2081}, mesh = {COVID-19/epidemiology/psychology/*rehabilitation ; Female ; Humans ; Male ; Pandemics ; Quality of Life ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: COVID-19 can result in a broad spectrum of dysfunctions, some of which may persist for long periods, requiring long-term rehabilitation. A comprehensive screening tool is therefore necessary to identify these needs. To date, no data exist on satisfaction with medical and therapeutic interventions for COVID-19 in terms of quality and quantity. The aim of this study is to develop a survey for use with COVID-19 patients during and after the end of the acute phase of the disease.

METHODS: Following the definition of dimensions by a group of experts, and a literature search, proven survey instruments were searched for suitable items. In addition, specific questions were developed based on symptoms, and answer options were created with regard to to the complexity of the questions.

RESULTS: The COVID-19 Rehabilitation Needs Survey (C19-RehabNeS) consists of the established 36-item Short Form Survey (SF-36) together with the newly developed COVID-19-Rehabilitation Needs Questionnaire (C19-RehabNeQ) (11 further dimensions, respectively 57 items).

CONCLUSION: C19-RehabNeS is a comprehensive survey to assess functional limitations and rehabilitation needs during and after infection with SARS-CoV-2 (COVID-19). The strength of this survey is that it combines the assessment of important rehabilitation needs with assessment of satisfaction with the health services, treatment and therapy during the pandemic (C19-RehabNeQ) and assessment of patients' quality of life (SF-36). The C19-RehabNeS survey also enables collection of systematic information on patients with Post-COVID-19 syndrome (Long-COVID-19).}, } @article {pmid33764205, year = {2021}, author = {Punjabi, PP}, title = {Long COVID - Education, Science, Innovation and Training.}, journal = {Perfusion}, volume = {36}, number = {2}, pages = {111-112}, doi = {10.1177/0267659121999898}, pmid = {33764205}, issn = {1477-111X}, mesh = {*COVID-19/complications ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33762402, year = {2021}, author = {Ladds, E and Rushforth, A and Wieringa, S and Taylor, S and Rayner, C and Husain, L and Greenhalgh, T}, title = {Erratum: Developing services for long COVID: lessons from a study of wounded healers.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {2}, pages = {160}, doi = {10.7861/clinmed.err.21.2}, pmid = {33762402}, issn = {1473-4893}, } @article {pmid33752388, year = {2021}, author = {Radvan, M and Bartečků, E and Sýkorová, U and Pařízková, R and Richter, S and Kameník, M and Koc, L and Kala, P}, title = {[Follow-up care after COVID-19 and its related concerns].}, journal = {Vnitrni lekarstvi}, volume = {67}, number = {1}, pages = {30-36}, pmid = {33752388}, issn = {0042-773X}, mesh = {*Aftercare ; *COVID-19 ; Czech Republic ; Humans ; Pandemics ; SARS-CoV-2 ; }, abstract = {Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). Overall COVID-19-related rates of mortality are low; deaths usually occur in patients older than 60 and those suffering from serious chronic diseases. Most of the patients recover within one or two weeks. However, in approximately 5-10 % of the patients some of the symptoms persist for weeks and months. Post-COVID-19 syndrome is a multisystem disease with overlapping symptoms and may occur even in patients who were relatively mildly affected during the acute phase of the disease. Evaluating the number of patients with or after the novel coronavirus infection in the Czech Republic, it can be estimated that in the next months there will be about 50,000 new patients suffering from long-COVID-19 requiring attention of general practitioners in the least, and, in all probability, also of other medical specialists. A thorough knowledge of the syndrome and efficient ideally evidence-based guidelines have to be formulated to combat the adverse impact of the pandemic.}, } @article {pmid33749957, year = {2021}, author = {Taylor, AK and Kingstone, T and Briggs, TA and O'Donnell, CA and Atherton, H and Blane, DN and Chew-Graham, CA}, title = {'Reluctant pioneer': A qualitative study of doctors' experiences as patients with long COVID.}, journal = {Health expectations : an international journal of public participation in health care and health policy}, volume = {24}, number = {3}, pages = {833-842}, pmid = {33749957}, issn = {1369-7625}, mesh = {COVID-19/*complications/epidemiology ; Emotions ; Humans ; Interviews as Topic ; Pandemics ; Physicians/*psychology ; Qualitative Research ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: The coronavirus disease (COVID-19) pandemic has had far-reaching effects upon lives, healthcare systems and society. Some who had an apparently 'mild' COVID-19 infection continue to suffer from persistent symptoms, including chest pain, breathlessness, fatigue, cognitive impairment, paraesthesia, muscle and joint pains. This has been labelled 'long COVID'. This paper reports the experiences of doctors with long COVID.

METHODS: A qualitative study; interviews with doctors experiencing persistent symptoms were conducted by telephone or video call. Interviews were transcribed and analysis conducted using an inductive and thematic approach.

RESULTS: Thirteen doctors participated. The following themes are reported: making sense of symptoms, feeling let down, using medical knowledge and connections, wanting to help and be helped, combining patient and professional identity. Experiencing long COVID can be transformative: many expressed hope that good would come of their experiences. Distress related to feelings of being 'let down' and the hard work of trying to access care. Participants highlighted that they felt better able to care for, and empathize with, patients with chronic conditions, particularly where symptoms are unexplained.

CONCLUSIONS: The study adds to the literature on the experiences of doctors as patients, in particular where evidence is emerging and the patient has to take the lead in finding solutions to their problems and accessing their own care.

The study was developed with experts by experience (including co-authors HA and TAB) who contributed to the protocol and ethics application, and commented on analysis and implications. All participants were given the opportunity to comment on findings.}, } @article {pmid33743226, year = {2021}, author = {The Lancet Neurology, }, title = {Long COVID: understanding the neurological effects.}, journal = {The Lancet. Neurology}, volume = {20}, number = {4}, pages = {247}, doi = {10.1016/S1474-4422(21)00059-4}, pmid = {33743226}, issn = {1474-4465}, mesh = {COVID-19/*complications ; Humans ; Nervous System Diseases/*virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33740207, year = {2021}, author = {Raj, SR and Arnold, AC and Barboi, A and Claydon, VE and Limberg, JK and Lucci, VM and Numan, M and Peltier, A and Snapper, H and Vernino, S and , }, title = {Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.}, journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society}, volume = {31}, number = {3}, pages = {365-368}, pmid = {33740207}, issn = {1619-1560}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; K99 HL122507/HL/NHLBI NIH HHS/United States ; }, mesh = {COVID-19/*complications ; Humans ; Postural Orthostatic Tachycardia Syndrome/*etiology/therapy ; Societies, Medical ; United States ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.}, } @article {pmid33728822, year = {2021}, author = {Menzella, F and Barbieri, C and Fontana, M and Scelfo, C and Castagnetti, C and Ghidoni, G and Ruggiero, P and Livrieri, F and Piro, R and Ghidorsi, L and Montanari, G and Gibellini, G and Casalini, E and Falco, F and Catellani, C and Facciolongo, N}, title = {Effectiveness of noninvasive ventilation in COVID-19 related-acute respiratory distress syndrome.}, journal = {The clinical respiratory journal}, volume = {15}, number = {7}, pages = {779-787}, pmid = {33728822}, issn = {1752-699X}, mesh = {*COVID-19 ; Female ; Humans ; Male ; *Noninvasive Ventilation ; Pandemics ; *Respiratory Distress Syndrome/therapy ; *Respiratory Insufficiency/therapy ; SARS-CoV-2 ; }, abstract = {INTRODUCTION: During this long COVID-19 pandemic outbreak, continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are being widely used to treat patients with moderate to severe acute respiratory failure (ARF). As for now, data on the efficacy of NIV in COVID-19 acute respiratory distress syndrome (ARDS) are lacking, and for this reason it is extremely important to accurately determine the outcomes of this strategy. This study aimed to evaluate clinical data and outcomes of NIV in patients with COVID-19 ARDS.

MATHERIALS AND METHODS: Seventy-nine consecutive patients with sudden worsening of respiratory failure were evaluated. All patients (71% male) had a confirmed SARS-CoV-2 infection and signs, symptoms and radiological findings compatible with COVID-19 pneumonia and all of them underwent a trial of NIV. Primary outcomes were NIV success and failure defined by intubation and mortality rate. Secondary outcome was the duration of NIV.

RESULTS: NIV was successful in 38 (48.1%) patients (Table 1). EOT was necessary in 21 patients (26.6%). Death occurred in 20 patients (25.3%). In the group of patients having failed a trial with NIV and then being intubated, compared to those who continued NIV, there was no higher mortality rate. By evaluating the ICU survival outcome of the subgroup of patients intubated after NIV, 57% of the patients were discharged and 43% died.

CONCLUSION: Previous studies conducted on patients undergoing invasive mechanical ventilation showed higher mortality rate than the present study. Our data showed that NIV can avoid intubation in almost half of the patients. Therefore, this data could reassure clinicians who would consider using NIV in COVID-19 ARDS-related treatment.}, } @article {pmid33722798, year = {2021}, author = {Altmann, DM}, title = {Children and the return to school: how much should we worry about covid-19 and long covid?.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n701}, doi = {10.1136/bmj.n701}, pmid = {33722798}, issn = {1756-1833}, support = {MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid33713306, year = {2022}, author = {Doherty, AM and Colleran, GC and Durcan, L and Irvine, AD and Barrett, E}, title = {A pilot study of burnout and long covid in senior specialist doctors.}, journal = {Irish journal of medical science}, volume = {191}, number = {1}, pages = {133-137}, pmid = {33713306}, issn = {1863-4362}, mesh = {*Burnout, Professional/epidemiology ; Burnout, Psychological/epidemiology ; *COVID-19/complications ; Cross-Sectional Studies ; Humans ; Pandemics ; Pilot Projects ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Covid-19 has placed unprecedented demand on healthcare systems and on healthcare professionals. There have been concerns about the risk of distress, moral injury and burnout among healthcare professionals, especially doctors.

AIM: To assess the effect of the ongoing Covid-19 pandemic on Irish doctors by investigating the incidence of burnout and long covid among senior medical staff in Ireland.

METHODS: This is a cross-sectional pilot study of the prevalence of burnout and long covid among senior physicians. A survey was sent by email to members of the Irish Hospital Consultant's Association. The survey included measures of mental and physical health and the 2-item Maslach Burnout Scale (MBS-2). The study explored the experience of delivering health care in the context of a pandemic and experience of the long covid syndrome.

RESULTS: A total of 114 responses were received. Three-quarters 77% (N = 88) screened positive for burnout on the MBS, with mean score of 5.6 (SD3.3), nearly double the cut-off for burnout. Nearly two-thirds (64%, n = 72) reported that Covid-19 has had an adverse effect on their mental health. One-quarter reported that they or colleagues had experience of 'long-covid' secondary to the virus.

CONCLUSION: More comprehensive evaluation of the effect of the pandemic on front-line staff is needed to identify the extent of the problem and the factors which contribute to it. This will inform measures to mitigate these effects.}, } @article {pmid33705725, year = {2021}, author = {Mehta, P and Bunker, CB and Ciurtin, C and Porter, JC and Chambers, RC and Papdopoulou, C and Garthwaite, H and Hillman, T and Heightman, M and Howell, KJ and Eleftheriou, D and Denton, CP}, title = {Chilblain-like acral lesions in long COVID-19: management and implications for understanding microangiopathy.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {7}, pages = {912}, pmid = {33705725}, issn = {1474-4457}, support = {MC_PC_20022/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*COVID-19/complications ; *Chilblains/diagnosis ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33692530, year = {2021}, author = {Sudre, CH and Murray, B and Varsavsky, T and Graham, MS and Penfold, RS and Bowyer, RC and Pujol, JC and Klaser, K and Antonelli, M and Canas, LS and Molteni, E and Modat, M and Jorge Cardoso, M and May, A and Ganesh, S and Davies, R and Nguyen, LH and Drew, DA and Astley, CM and Joshi, AD and Merino, J and Tsereteli, N and Fall, T and Gomez, MF and Duncan, EL and Menni, C and Williams, FMK and Franks, PW and Chan, AT and Wolf, J and Ourselin, S and Spector, T and Steves, CJ}, title = {Attributes and predictors of long COVID.}, journal = {Nature medicine}, volume = {27}, number = {4}, pages = {626-631}, pmid = {33692530}, issn = {1546-170X}, support = {/WT_/Wellcome Trust/United Kingdom ; 203148/WT_/Wellcome Trust/United Kingdom ; K23 DK120899/DK/NIDDK NIH HHS/United States ; AS-JF-17-011/ALZS_/Alzheimer's Society/United Kingdom ; }, mesh = {Adult ; Age Factors ; Aged ; COVID-19/*complications ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; *SARS-CoV-2 ; Time Factors ; }, abstract = {Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app[1]. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.}, } @article {pmid33692189, year = {2021}, author = {Humphreys, H and Kilby, L and Kudiersky, N and Copeland, R}, title = {Long COVID and the role of physical activity: a qualitative study.}, journal = {BMJ open}, volume = {11}, number = {3}, pages = {e047632}, pmid = {33692189}, issn = {2044-6055}, mesh = {*Activities of Daily Living ; Adolescent ; Adult ; Aged ; COVID-19/*complications ; *Exercise ; Female ; Humans ; Male ; Middle Aged ; Qualitative Research ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {OBJECTIVES: To explore the lived experience of long COVID with particular focus on the role of physical activity.

DESIGN: Qualitative study using semistructured interviews.

PARTICIPANTS: 18 people living with long COVID (9 men, 9 women; aged between 18-74 years; 10 white British, 3 white Other, 3 Asian, 1 black, 1 mixed ethnicity) recruited via a UK-based research interest database for people with long COVID.

SETTING: Telephone interviews with 17 participants living in the UK and 1 participant living in the USA.

RESULTS: Four themes were generated. Theme 1 describes how participants struggled with drastically reduced physical function, compounded by the cognitive and psychological effects of long COVID. Theme 2 highlights challenges associated with finding and interpreting advice about physical activity that was appropriately tailored. Theme 3 describes individual approaches to managing symptoms including fatigue and 'brain fog' while trying to resume and maintain activities of daily living and other forms of exercise. Theme 4 illustrates the battle with self-concept to accept reduced function (even temporarily) and the fear of permanent reduction in physical and cognitive ability.

CONCLUSIONS: This study provides insight into the challenges of managing physical activity alongside the extended symptoms associated with long COVID. Findings highlight the need for greater clarity and tailoring of physical activity-related advice for people with long COVID and improved support to resume activities important to individual well-being.}, } @article {pmid33688642, year = {2021}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Perelman, C and Sepulveda, R and Rebolledo, P and Cuapio, A and Villapol, S}, title = {More Than 50 Long-Term Effects of COVID-19: A Systematic Review and Meta-Analysis.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {33688642}, issn = {2693-5015}, support = {R21 NS106640/NS/NINDS NIH HHS/United States ; }, abstract = {Background. COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. Methods . LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1 [st] of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I [2] statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. Results. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). Conclusions . In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, the severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.}, } @article {pmid33686318, year = {2021}, author = {Thomson, H}, title = {Children with long covid.}, journal = {New scientist (1971)}, volume = {249}, number = {3323}, pages = {10-11}, doi = {10.1016/S0262-4079(21)00303-1}, pmid = {33686318}, issn = {0262-4079}, abstract = {Almost half of children who contract covid-19 may have lasting symptoms, which should factor into decisions on reopening schools, reports Helen Thomson.}, } @article {pmid33685823, year = {2021}, author = {Cardona, G and Alonso, S and Busquets, A}, title = {Patient - practitioner communication and contact lens compliance during a prolonged COVID-19 lockdown.}, journal = {Contact lens & anterior eye : the journal of the British Contact Lens Association}, volume = {44}, number = {6}, pages = {101433}, pmid = {33685823}, issn = {1476-5411}, mesh = {*COVID-19/complications ; Communicable Disease Control ; Communication ; Contact Lens Solutions ; *Contact Lenses, Hydrophilic ; Humans ; Patient Compliance ; Retrospective Studies ; SARS-CoV-2 ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: Ocular manifestations and ocular transmission of SARS-CoV-2 in contact lens (CL) wearers may be fostered by non-compliance with care and maintenance instructions which, in turn, may be aggravated by inadequate patient-practitioner communication. The purpose of this research was to determine CL use, compliance and patient-practitioner communication during a 3-month long COVID-19 lockdown in Spain.

METHODS: An online survey (developed using Google Forms) retrospectively evaluated CL compliance during the 3-month lockdown (responses captured between 15th July and 10th August, 2020), with particular emphasis on patient-practitioner communication, handwashing practices and CL case hygiene and replacement.

RESULTS: A total of 247 responses were collected and analysed. Most participants used monthly replacement soft lenses (64.8 %) and multipurpose solutions (75.7 %), with 86.6 % of them owning a storage case for their lenses. During lockdown, a significant percentage of participants ceased lens wear (28.4 %) or reduced wearing time (49.2 %). Regarding patient-practitioner communication, 54.3 % of respondents received specific instructions, mostly about handwashing (93.3 %) and storage case hygiene (48.5 %). The most frequent non-compliant practices were inadequate handwashing (36.4 %), and overextending monthly or two-weekly replacement lenses (35.2 %). Many respondents never cleaned (23.0 %) nor replaced (16.3 %) their storage case, and 27.8 % of them reported not having been informed about case hygiene by their practitioners.

CONCLUSION: Contact lens compliance, particularly in terms of handwashing and storage case hygiene, was poor during a prolonged COVID-19 lockdown, thus stressing the need to foster patient-practitioner communication strategies to curtail the possibility of ocular transmission and the risk of virus tropism.}, } @article {pmid33680620, year = {2021}, author = {Iqbal, A and Iqbal, K and Arshad Ali, S and Azim, D and Farid, E and Baig, MD and Bin Arif, T and Raza, M}, title = {The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors.}, journal = {Cureus}, volume = {13}, number = {2}, pages = {e13080}, pmid = {33680620}, issn = {2168-8184}, abstract = {Background As of January 19, 2021, around two million fatalities and 68 million recoveries from coronavirus disease 2019 (COVID-19) have been reported around the globe. The past pandemics of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) hint toward a risk of occurrence of "Long-COVID" syndrome, i.e., the persistence of post-discharge symptoms among COVID-19 survivors. With the scarcity of literature addressing post-COVID-19 manifestations and little regard for the stigma associated with this disease, survivors' rehabilitation remains widely neglected. The current study aims to assess the prevalence and characteristics of post-COVID-19 manifestations and their effect on the quality of life (QoL) of COVID-19 recovered individuals. We have also analyzed the relationship of time since the recovery of COVID-19 and its severity with the post-discharge symptoms. The stigma affiliated with the infection of SARS coronavirus-2 (SARS-CoV-2) has also been highlighted. Methodology A descriptive, cross-sectional, questionnaire-based study was conducted from September 2020 to December 2020 among 158 COVID-19 recovered patients, whose information was obtained from Dow Diagnostic Laboratory, Ojha Campus, Karachi, Pakistan. The questionnaire consisted of four sections: sociodemographic data, post-COVID-19 manifestations, questions relating to the stigma, and the QoL of the recovered COVID-19 patients. We used the EuroQol five-dimension five-level questionnaire to assess the QoL, while the modified BG Prasad Socioeconomic Classification updated for 2019 was employed to determine the socioeconomic status of the participants. Data were analyzed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA). Data were presented in the form of frequencies and percentages. Results An overwhelming majority (94.9%) experienced at least one post-COVID-19 symptom, with fatigue (82.9%) being the most prevalent post-discharge manifestation. We observed a significant correlation of post-COVID-19 symptoms with gender, age, and time since recovery. COVID-19 severity was found to be significantly related to the five dimensions of the QoL. A significant difference in EuroQol Visual Analog Scale health score was observed between the participants with mild, moderate, and severe COVID-19 infection (p < 0.001). Besides, the associated stigma with SARS-CoV-2 infection was found to be more prevalent in the participants belonging to the upper class as compared to the other classes (p < 0.05). Nonetheless, we also observed a significant association of disease severity with post-COVID-19 manifestations and pre-existing comorbidities. Conclusions The long-COVID syndrome is similar to the post-discharge manifestations of the survivors of prior pandemics of SARS and MERS. Multi-disciplinary rehabilitation teams, healthcare workers, and the general population should recognize the need for systematic assessment of their recovery and further rehabilitation.}, } @article {pmid33677642, year = {2021}, author = {Sollini, M and Morbelli, S and Ciccarelli, M and Cecconi, M and Aghemo, A and Morelli, P and Chiola, S and Gelardi, F and Chiti, A}, title = {Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {48}, number = {10}, pages = {3187-3197}, pmid = {33677642}, issn = {1619-7089}, mesh = {Adult ; *COVID-19/complications ; Case-Control Studies ; *Fluorodeoxyglucose F18 ; Humans ; Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: The present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID.

METHODS: We prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly.

RESULTS: In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level).

CONCLUSION: [18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several "target" and "non-target" tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.}, } @article {pmid33675686, year = {2021}, author = {Kirby, T}, title = {Young person with long COVID after mild disease.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {5}, pages = {453-455}, doi = {10.1016/S2213-2600(21)00123-5}, pmid = {33675686}, issn = {2213-2619}, mesh = {Adult ; Aftercare/*methods ; COVID-19/*complications/physiopathology/psychology/therapy ; *Fatigue Syndrome, Chronic/etiology/psychology ; Female ; Humans ; Ireland ; *Mental Fatigue/etiology/physiopathology ; Mental Health ; SARS-CoV-2 ; Self-Help Groups ; Severity of Illness Index ; *Social Support ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33675366, year = {2021}, author = {Pereira, C and Harris, BHL and Di Giovannantonio, M and Rosadas, C and Short, CE and Quinlan, R and Sureda-Vives, M and Fernandez, N and Day-Weber, I and Khan, M and Marchesin, F and Katsanovskaja, K and Parker, E and Taylor, GP and Tedder, RS and McClure, MO and Dani, M and Fertleman, M}, title = {The Association Between Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Post-COVID-19 Syndrome in Healthcare Workers.}, journal = {The Journal of infectious diseases}, volume = {223}, number = {10}, pages = {1671-1676}, pmid = {33675366}, issn = {1537-6613}, support = {MC_PC_19078/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Adult ; Aged ; Anosmia ; Antibodies, Viral/*biosynthesis ; COVID-19/*complications/immunology ; Cohort Studies ; Fatigue ; Female ; Headache ; *Health Personnel ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Nasopharynx/virology ; Respiratory Tract Diseases ; SARS-CoV-2/*immunology ; Surveys and Questionnaires ; Syndrome ; United Kingdom ; Young Adult ; }, abstract = {It is currently unknown how post-COVID-19 syndrome (PCS) may affect those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This longitudinal study includes healthcare staff who tested positive for SARS-CoV-2 between March and April 2020, with follow-up of their antibody titers and symptoms. More than half (21 of 38) had PCS after 7-8 months. There was no statistically significant difference between initial reverse-transcription polymerase chain reaction titers or serial antibody levels between those who did and those who did not develop PCS. This study highlights the relative commonality of PCS in healthcare workers and this should be considered in vaccination scheduling and workforce planning to allow adequate frontline staffing numbers.}, } @article {pmid33664445, year = {2021}, author = {Subbaraman, N}, title = {US health agency will invest $1 billion to investigate 'long COVID'.}, journal = {Nature}, volume = {591}, number = {7850}, pages = {356}, pmid = {33664445}, issn = {1476-4687}, mesh = {Anxiety ; Autopsy ; Biological Specimen Banks/organization & administration ; Biomedical Research/*economics/*trends ; COVID-19/*complications/epidemiology/pathology/physiopathology/therapy ; Depression ; Disease Susceptibility ; Dyspnea ; Fatigue ; Fever ; *Goals ; Humans ; Longitudinal Studies ; Monitoring, Physiologic ; National Institutes of Health (U.S.)/*economics/organization & administration ; Organ Specificity ; Research Support as Topic/*economics/organization & administration ; Time Factors ; United States ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33657459, year = {2021}, author = {McCaddon, A and Regland, B}, title = {COVID-19: A methyl-group assault?.}, journal = {Medical hypotheses}, volume = {149}, number = {}, pages = {110543}, pmid = {33657459}, issn = {1532-2777}, mesh = {Adenosine/analogs & derivatives/chemistry ; COVID-19/blood/*complications/physiopathology ; Folic Acid/*blood ; Folic Acid Deficiency ; Formates/blood ; Genome, Viral ; Glutathione/blood ; Homocysteine/blood ; Hospitalization ; Humans ; Methylation ; Methylmalonic Acid/blood ; Oxidative Stress ; RNA/chemistry ; Serine/blood ; Vitamin B 12/blood ; Vitamin B 12 Deficiency/*diagnosis ; Post-Acute COVID-19 Syndrome ; }, abstract = {The socio-economic implications of COVID-19 are devastating. Considerable morbidity is attributed to 'long-COVID' - an increasingly recognized complication of infection. Its diverse symptoms are reminiscent of vitamin B12 deficiency, a condition in which methylation status is compromised. We suggest why SARS-CoV-2 infection likely leads to increased methyl-group requirements and other disturbances of one-carbon metabolism. We propose these might explain the varied symptoms of long-COVID. Our suggested mechanismmight also apply to similar conditions such as myalgic encephalomyelitis/chronic fatigue syndrome. The hypothesis is evaluable by detailed determination of vitamin B12and folate status, including serum formate as well as homocysteine and methylmalonic acid, and correlation with viral and host RNA methylation and symptomatology. If confirmed, methyl-group support should prove beneficial in such individuals.}, } @article {pmid33649741, year = {2021}, author = {Iqbal, FM and Lam, K and Sounderajah, V and Elkin, S and Ashrafian, H and Darzi, A}, title = {Understanding the survivorship burden of long COVID.}, journal = {EClinicalMedicine}, volume = {33}, number = {}, pages = {100767}, pmid = {33649741}, issn = {2589-5370}, support = {MC_PC_18032/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid33649174, year = {2021}, author = {Murray, T}, title = {Unpacking "long COVID".}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {193}, number = {9}, pages = {E318-E319}, doi = {10.1503/cmaj.1095923}, pmid = {33649174}, issn = {1488-2329}, mesh = {COVID-19/*complications/economics/*epidemiology ; *Health Care Costs ; Humans ; *SARS-CoV-2 ; State Medicine ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33634830, year = {2021}, author = {Burgess, LC and Venugopalan, L and Badger, J and Street, T and Alon, G and Jarvis, JC and Wainwright, TW and Everington, T and Taylor, P and Swain, ID}, title = {Effect of neuromuscular electrical stimulation on the recovery of people with COVID-19 admitted to the intensive care unit: A narrative review.}, journal = {Journal of rehabilitation medicine}, volume = {53}, number = {3}, pages = {jrm00164}, pmid = {33634830}, issn = {1651-2081}, mesh = {COVID-19/rehabilitation/*therapy/virology ; Clinical Trials as Topic ; Electric Stimulation Therapy/*methods ; Hospitalization ; Humans ; Intensive Care Units ; Randomized Controlled Trials as Topic ; SARS-CoV-2/isolation & purification ; }, abstract = {The rehabilitation of patients with COVID-19 after prolonged treatment in the intensive care unit is often complex and challenging. Patients may develop a myriad of long-term multiorgan impairments, affecting the respiratory, cardiac, neurological, digestive and musculoskeletal systems. Skeletal muscle dysfunction of respiratory and limb muscles, commonly referred to as intensive care unit acquired weakness, occurs in approximately 40% of all patients admitted to intensive care. The impact on mobility and return to activities of daily living is severe. Furthermore, many patients experience ongoing symptoms of fatigue, weakness and shortness of breath, in what is being described as "long COVID". Neuromuscular electrical stimulation is a technique in which small electrical impulses are applied to skeletal muscle to cause contractions when voluntary muscle contraction is difficult or impossible. Neuromuscular electrical stimulation can prevent muscle atrophy, improve muscle strength and function, maintain blood flow and reduce oedema. This review examines the evidence, current guidelines, and proposed benefits of using neuromuscular electrical stimulation with patients admitted to the intensive care unit. Practical recommendations for using electrical muscle stimulation in patients with COVID-19 are provided, and suggestions for further research are proposed. Evidence suggests NMES may play a role in the weaning of patients from ventilators and can be continued in the post-acute and longer-term phases of recovery. As such, NMES may be a suitable treatment modality to implement within rehabilitation pathways for COVID-19, with consideration of the practical and safety issues highlighted within this review.}, } @article {pmid33633106, year = {2021}, author = {Stefano, GB}, title = {Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e931447}, pmid = {33633106}, issn = {1643-3750}, mesh = {Brain/virology ; COVID-19/*complications/epidemiology/metabolism/*physiopathology/*psychology ; Cognitive Dysfunction/physiopathology/virology ; History, 21st Century ; Humans ; Influenza Pandemic, 1918-1919 ; Pandemics ; SARS-CoV-2/enzymology/isolation & purification/metabolism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term "long COVID". A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition. In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in "brain fog". Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). There are similarities between chronic fatigue syndrome and the "brain fog" described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.}, } @article {pmid33632171, year = {2021}, author = {Makaronidis, J and Firman, C and Magee, CG and Mok, J and Balogun, N and Lechner, M and Carnemolla, A and Batterham, RL}, title = {Distorted chemosensory perception and female sex associate with persistent smell and/or taste loss in people with SARS-CoV-2 antibodies: a community based cohort study investigating clinical course and resolution of acute smell and/or taste loss in people with and without SARS-CoV-2 antibodies in London, UK.}, journal = {BMC infectious diseases}, volume = {21}, number = {1}, pages = {221}, pmid = {33632171}, issn = {1471-2334}, support = {RP-2015-06-005/DH_/Department of Health/United Kingdom ; BRC751//National Institute for Health Research/ ; NA//Sir Jules Thorn Charitable Trust/ ; RP-2015-06-005//Health Technology Assessment Programme/ ; }, mesh = {Adult ; Ageusia/*etiology ; Antibodies, Viral/*blood ; COVID-19/*complications ; Cohort Studies ; Female ; Humans ; Immunoglobulin M/blood ; London ; Male ; Middle Aged ; Olfaction Disorders/diagnosis/*etiology ; SARS-CoV-2 ; Sex Factors ; Smell ; Surveys and Questionnaires ; Treatment Outcome ; }, abstract = {BACKGROUND: Loss of smell and/or taste are cardinal symptoms of COVID-19. 'Long-COVID', persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4-6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants.

METHODS: Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4-6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations.

RESULTS: People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4-6 weeks (OR 2.46, 95%CI 1.47-4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54-4.00, p < 0.001).

CONCLUSION: Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4-6 weeks follow-up, which constitute symptoms of 'long-COVID'. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions.

TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815 Date of registration: 23/04/2020.}, } @article {pmid33627337, year = {2021}, author = {Bhopal, SS and Absoud, M}, title = {Vaccinating children to prevent long covid? More caution is needed in interpreting current epidemiological data.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n520}, doi = {10.1136/bmj.n520}, pmid = {33627337}, issn = {1756-1833}, mesh = {Adolescent ; Age Factors ; COVID-19/*complications/diagnosis/epidemiology/prevention & control ; *COVID-19 Vaccines ; Child ; Child, Preschool ; Humans ; Symptom Assessment ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33625001, year = {2021}, author = {}, title = {NewsCAP: Autoantibody reactivity implicated in 'long' COVID-19.}, journal = {The American journal of nursing}, volume = {121}, number = {3}, pages = {17}, doi = {10.1097/01.NAJ.0000737260.41769.52}, pmid = {33625001}, issn = {1538-7488}, mesh = {Autoantibodies ; *COVID-19 ; Humans ; SARS-CoV-2 ; }, } @article {pmid33624010, year = {2021}, author = {Jacobson, KB and Rao, M and Bonilla, H and Subramanian, A and Hack, I and Madrigal, M and Singh, U and Jagannathan, P and Grant, P}, title = {Patients With Uncomplicated Coronavirus Disease 2019 (COVID-19) Have Long-Term Persistent Symptoms and Functional Impairment Similar to Patients with Severe COVID-19: A Cautionary Tale During a Global Pandemic.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {3}, pages = {e826-e829}, doi = {10.1093/cid/ciab103}, pmid = {33624010}, issn = {1537-6591}, support = {R25 AI147369/AI/NIAID NIH HHS/United States ; U01 AI150741/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19 ; COVID-19 Testing ; Humans ; *Pandemics ; SARS-CoV-2 ; Surveys and Questionnaires ; }, abstract = {To assess the prevalence of persistent functional impairment after coronavirus disease (COVID-19), we assessed 118 individuals 3-4 months after their initial COVID-19 diagnosis with a symptom survey, work productivity and activity index questionnaire, and 6-minute walk test. We found significant persistent symptoms and functional impairment, even in non-hospitalized patients with COVID-19.}, } @article {pmid33622802, year = {2021}, author = {Ballering, A and Olde Hartman, T and Rosmalen, J}, title = {Long COVID-19, persistent somatic symptoms and social stigmatisation.}, journal = {Journal of epidemiology and community health}, volume = {75}, number = {6}, pages = {603-604}, pmid = {33622802}, issn = {1470-2738}, } @article {pmid33621843, year = {2021}, author = {Jacobs, JJL}, title = {Persistent SARS-2 infections contribute to long COVID-19.}, journal = {Medical hypotheses}, volume = {149}, number = {}, pages = {110538}, pmid = {33621843}, issn = {1532-2777}, mesh = {Antibodies, Viral/immunology ; Antiviral Agents/therapeutic use ; Autoimmunity ; COVID-19/*complications/immunology/virology ; Cytokine Release Syndrome ; Humans ; Inflammation ; Models, Theoretical ; *SARS-CoV-2 ; Superantigens/immunology ; *Virus Shedding ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19 is a serious disease that has infected more than 40 million people. Beside significant mortality, the SARS-CoV-2 infection causes considerable and sustained morbidity, dubbed long COVID. This paper argues that some of this morbidity may be due to a persistent systemic infection. Persistent infection is indicated by continued virus RNA shedding. The virus' superantigen could overstimulate anti-virus immune responses, and thereby induce negative feedback loops, that paradoxically allow the virus to persist. The superantigen would induce strong immune response to any residual infection. This hypothesis suggests that clearing the virus infection completely would be an appropriate intervention against long COVID.}, } @article {pmid33619477, year = {2021}, author = {Reiken, S and Dridi, H and Sittenfeld, L and Liu, X and Marks, AR}, title = {Alzheimer's-like remodeling of neuronal ryanodine receptor in COVID-19.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2021.02.18.431811}, pmid = {33619477}, issn = {2692-8205}, abstract = {COVID-19, caused by SARS-CoV-2 involves multiple organs including cardiovascular, pulmonary and central nervous system. Understanding how SARS-CoV-2 infection afflicts diverse organ systems remains challenging [1,2] . Particularly vexing has been the problem posed by persistent organ dysfunction known as "long COVID," which includes cognitive impairment [3] . Here we provide evidence linking SARS-CoV-2 infection to activation of TGF-ß signaling and oxidative overload. One consequence is oxidation of the ryanodine receptor/calcium (Ca [2+]) release channels (RyR) on the endo/sarcoplasmic (ER/SR) reticuli in heart, lung and brains of patients who succumbed to COVID-19. This depletes the channels of the stabilizing subunit calstabin2 causing them to leak Ca [2+] which can promote heart failure [4,5] , pulmonary insufficiency [6] and cognitive and behavioral defects [7-9] . Ex-vivo treatment of heart, lung, and brain tissues from COVID-19 patients using a Rycal drug (ARM210) [10] prevented calstabin2 loss and fixed the channel leak. Of particular interest is that neuropathological pathways activated downstream of leaky RyR2 channels in Alzheimer's Disease (AD) patients were activated in COVID-19 patients. Thus, leaky RyR2 Ca [2+] channels may play a role in COVID-19 pathophysiology and could be a therapeutic target for amelioration of some comorbidities associated with SARS-CoV-2 infection.}, } @article {pmid33609255, year = {2023}, author = {Oronsky, B and Larson, C and Hammond, TC and Oronsky, A and Kesari, S and Lybeck, M and Reid, TR}, title = {A Review of Persistent Post-COVID Syndrome (PPCS).}, journal = {Clinical reviews in allergy & immunology}, volume = {64}, number = {1}, pages = {66-74}, pmid = {33609255}, issn = {1559-0267}, mesh = {Humans ; *COVID-19 ; Disease Progression ; Immunosuppression Therapy ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; }, abstract = {Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.}, } @article {pmid33608317, year = {2021}, author = {Limb, M}, title = {Covid-19: Recognise long covid as occupational disease and compensate frontline workers, say MPs.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n503}, doi = {10.1136/bmj.n503}, pmid = {33608317}, issn = {1756-1833}, } @article {pmid33604323, year = {2020}, author = {Barin, B and Yoldascan, BE and Savaskan, F and Ozbalikci, G and Karaderi, T and Çakal, H}, title = {Joint Investigation of 2-Month Post-diagnosis IgG Antibody Levels and Psychological Measures for Assessing Longer Term Multi-Faceted Recovery Among COVID-19 Cases in Northern Cyprus.}, journal = {Frontiers in public health}, volume = {8}, number = {}, pages = {590096}, pmid = {33604323}, issn = {2296-2565}, mesh = {Adolescent ; Adult ; Antibodies, Viral/*blood ; Biomarkers/blood ; COVID-19/*immunology/psychology ; *COVID-19 Serological Testing ; Cyprus ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin G/*blood ; Male ; Middle Aged ; Psychological Tests ; SARS-CoV-2/*immunology ; }, abstract = {Following the outbreak of COVID-19, multidisciplinary research focusing on the long-term effects of the COVID-19 infection and the complete recovery is still scarce. With regards to long-term consequences, biomarkers of physiological effects as well as the psychological experiences are of significant importance for comprehensively understanding the complete COVID-19 recovery. The present research surveys the IgG antibody titers and the impact of COVID-19 as a traumatic experience in the aftermath of the active infection period, around 2 months after diagnosis, in a subset of COVID-19 patients from the first wave (March-April 2020) of the outbreak in Northern Cyprus. Associations of antibody titers and psychological survey measures with baseline characteristics and disease severity were explored, and correlations among various measures were evaluated. Of the 47 serology tests conducted for presence of IgG antibodies, 39 (83%) were positive. We identified trends demonstrating individuals experiencing severe or critical COVID-19 disease and/or those with comorbidities are more heavily impacted both physiologically and mentally, with higher IgG titers and negative psychological experience compared to those with milder disease and without comorbidities. We also observed that more than half of the COVID-19 cases had negative psychological experiences, being subjected to discrimination and verbal harassment/insult, by family/friends. In summary, as the first study co-evaluating immune response together with mental status in COVID-19, our findings suggest that further multidisciplinary research in larger sample populations as well as community intervention plans are needed to holistically address the physiological and psychological effects of COVID-19 among the cases.}, } @article {pmid33587810, year = {2021}, author = {Townsend, L and Fogarty, H and Dyer, A and Martin-Loeches, I and Bannan, C and Nadarajan, P and Bergin, C and O'Farrelly, C and Conlon, N and Bourke, NM and Ward, SE and Byrne, M and Ryan, K and O'Connell, N and O'Sullivan, JM and Ni Cheallaigh, C and O'Donnell, JS}, title = {Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {19}, number = {4}, pages = {1064-1070}, pmid = {33587810}, issn = {1538-7836}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Acute-Phase Reaction ; Aged ; COVID-19/*blood/rehabilitation ; Female ; Fibrin Fibrinogen Degradation Products/*analysis ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Persistent fatigue, breathlessness, and reduced exercise tolerance have been reported following acute COVID-19 infection. Although immuno-thrombosis has been implicated in acute COVID-19 pathogenesis, the biological mechanisms underpinning long COVID remain unknown. We hypothesized that pulmonary microvascular immuno-thrombosis may be important in this context.

METHODS: One hundred fifty COVID-19 patients were reviewed at St James's Hospital Dublin between May and September 2020 at a median of 80.5 (range 44-155) days after initial diagnosis. These included patients hospitalized during initial illness (n = 69) and others managed entirely as out-patients (n = 81). Clinical examination, chest x-ray, and 6-min walk tests were performed. In addition, a range of coagulation and inflammatory markers were assessed.

RESULTS: Increased D-dimer levels (>500 ng/ml) were observed in 25.3% patients up to 4 months post-SARS-CoV-2 infection. On univariate analysis, elevated convalescent D-dimers were more common in COVID-19 patients who had required hospital admission and in patients aged more than 50 years (p < .001). Interestingly, we observed that 29% (n = 11) of patients with elevated convalescent D-dimers had been managed exclusively as out-patients during their illness. In contrast, other coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen, platelet count) and inflammation (C-reactive protein, interleukin-6, and sCD25) markers had returned to normal in >90% of convalescent patients.

CONCLUSIONS: Elucidating the biological mechanisms responsible for sustained D-dimer increases may be of relevance in long COVID pathogenesis and has implications for clinical management of these patients.}, } @article {pmid33569660, year = {2021}, author = {Sykes, DL and Holdsworth, L and Jawad, N and Gunasekera, P and Morice, AH and Crooks, MG}, title = {Post-COVID-19 Symptom Burden: What is Long-COVID and How Should We Manage It?.}, journal = {Lung}, volume = {199}, number = {2}, pages = {113-119}, pmid = {33569660}, issn = {1432-1750}, mesh = {*Aftercare/methods/statistics & numerical data ; *Anxiety/diagnosis/etiology ; COVID-19/*complications/diagnosis/epidemiology/physiopathology/psychology/therapy ; *Cost of Illness ; *Fatigue/diagnosis/etiology ; Female ; Humans ; Male ; Middle Aged ; Models, Biopsychosocial ; Myalgia/diagnosis/etiology ; Patient Discharge ; SARS-CoV-2/isolation & purification/pathogenicity ; Sex Factors ; Symptom Assessment/methods/statistics & numerical data ; Telemedicine/methods ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome ; }, abstract = {The enduring impact of COVID-19 on patients has been examined in recent studies, leading to the description of Long-COVID. We report the lasting symptom burden of COVID-19 patients from the first wave of the pandemic. All patients with COVID-19 pneumonia discharged from a large teaching hospital trust were offered follow-up. We assessed symptom burden at follow-up using a standardised data collection technique during virtual outpatient clinic appointments. Eighty-six percent of patients reported at least one residual symptom at follow-up. No patients had persistent radiographic abnormalities. The presence of symptoms at follow-up was not associated with the severity of the acute COVID-19 illness. Females were significantly more likely to report residual symptoms including anxiety (p = 0.001), fatigue (p = 0.004), and myalgia (p = 0.022). The presence of long-lasting symptoms is common in COVID-19 patients. We suggest that the phenomenon of Long-COVID may not be directly attributable to the effect of SARS-CoV-2, and believe the biopsychosocial effects of COVID-19 may play a greater role in its aetiology.}, } @article {pmid33568362, year = {2021}, author = {Wise, J}, title = {Long covid: WHO calls on countries to offer patients more rehabilitation.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n405}, doi = {10.1136/bmj.n405}, pmid = {33568362}, issn = {1756-1833}, } @article {pmid33562427, year = {2021}, author = {Islam, MS and Ferdous, MZ and Islam, US and Mosaddek, ASM and Potenza, MN and Pardhan, S}, title = {Treatment, Persistent Symptoms, and Depression in People Infected with COVID-19 in Bangladesh.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {4}, pages = {}, pmid = {33562427}, issn = {1660-4601}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bangladesh/epidemiology ; COVID-19/*psychology/*therapy ; Cross-Sectional Studies ; Depression/*epidemiology ; Female ; Humans ; Male ; Middle Aged ; Self Medication ; Surveys and Questionnaires ; Young Adult ; }, abstract = {Background: Coronavirus disease (COVID-19) has affected people's lives globally. While important research has been conducted, much remains to be known. In Bangladesh, initial treatment (self-administered, hospitalized), persistent COVID-19 symptoms ("long COVID-19"), and whether COVID-19 leads to changes in mental state, such as depressive symptoms, of people are not known. This study aimed to examine treatment, persistent symptoms, and depression in people who had been infected with COVID-19 in Bangladesh. Methods: A cross-sectional survey was conducted on 1002 individuals infected with COVID-19 (60% male; mean age = 34.7 ± 13.9; age range = 18-81 years), with data taken over a one-month period (11 September 2020 to 13 October 2020). A self-reported online questionnaire was used to collect data on socio-demographics, lifestyle, COVID-19 symptoms (during and beyond COVID-19), medication (over-the-counter or doctor-prescribed), and depression (assessed using the Patient Health Questionnaire (PHQ-9)). Results: Twenty-four percent of participants self-medicated with over-the-counter medicine when they were first diagnosed with COVID-19. Self-medication was higher among female vs. male respondents (29.6% vs. 20.2%, respectively, p = 0.002). A minority (20%) reported that they experienced persistent COVID-like symptoms after recovering from COVID-19. The most reported persistent symptoms were diarrhea (12.7%) and fatigue (11.5%). Forty-eight percent of participants were categorized as having moderate to severe depression. Based on multivariate regression analysis, depression during COVID-19 was positively associated with lower family income, poor health status, sleep disturbance, lack of physical activity, hypertension, asthma/respiratory problems, fear of COVID-19 re-infection, and persistent COVID-19 symptoms. Conclusions: The findings suggest a need for appropriate interventions for COVID-19 patients to promote physical and mental wellbeing.}, } @article {pmid33548193, year = {2021}, author = {Norton, A and Olliaro, P and Sigfrid, L and Carson, G and Paparella, G and Hastie, C and Kaushic, C and Boily-Larouche, G and Suett, JC and O'Hara, M and , }, title = {Long COVID: tackling a multifaceted condition requires a multidisciplinary approach.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {5}, pages = {601-602}, pmid = {33548193}, issn = {1474-4457}, mesh = {*COVID-19 ; Humans ; Patient Care Team ; SARS-CoV-2 ; }, } @article {pmid33543709, year = {2021}, author = {Ashcroft, P and Lehtinen, S and Angst, DC and Low, N and Bonhoeffer, S}, title = {Quantifying the impact of quarantine duration on COVID-19 transmission.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33543709}, issn = {2050-084X}, support = {EpiPose,101003688//H2020 European Research Council/ ; EpiPose 101003688//H2020 European Research Council/ ; 176233/SNSF_/Swiss National Science Foundation/Switzerland ; 176401/SNSF_/Swiss National Science Foundation/Switzerland ; }, mesh = {COVID-19/*epidemiology/*transmission/virology ; Contact Tracing ; Humans ; *Models, Theoretical ; Pandemics ; Public Health Surveillance ; *Quarantine ; *SARS-CoV-2/physiology ; Time Factors ; }, abstract = {The large number of individuals placed into quarantine because of possible severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) exposure has high societal and economic costs. There is ongoing debate about the appropriate duration of quarantine, particularly since the fraction of individuals who eventually test positive is perceived as being low. We use empirically determined distributions of incubation period, infectivity, and generation time to quantify how the duration of quarantine affects onward transmission from traced contacts of confirmed SARS-CoV-2 cases and from returning travellers. We also consider the roles of testing followed by release if negative (test-and-release), reinforced hygiene, adherence, and symptoms in calculating quarantine efficacy. We show that there are quarantine strategies based on a test-and-release protocol that, from an epidemiological viewpoint, perform almost as well as a 10-day quarantine, but with fewer person-days spent in quarantine. The findings apply to both travellers and contacts, but the specifics depend on the context.}, } @article {pmid33541867, year = {2021}, author = {Altmann, DM and Boyton, RJ}, title = {Decoding the unknowns in long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n132}, doi = {10.1136/bmj.n132}, pmid = {33541867}, issn = {1756-1833}, support = {MR/S019553/1/MRC_/Medical Research Council/United Kingdom ; MR/V036939/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {COVID-19/*complications/virology ; Chronic Disease ; Humans ; Pandemics ; SARS-CoV-2/pathogenicity ; }, } @article {pmid33538586, year = {2021}, author = {Yong, SJ}, title = {Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.}, journal = {ACS chemical neuroscience}, volume = {12}, number = {4}, pages = {573-580}, doi = {10.1021/acschemneuro.0c00793}, pmid = {33538586}, issn = {1948-7193}, mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Brain Diseases/metabolism/*physiopathology/virology ; Brain Stem/blood supply/metabolism/*physiopathology/virology ; COVID-19/*complications/metabolism/physiopathology ; Humans ; Inflammation/metabolism/*physiopathology/virology ; Neuropilin-1/metabolism ; RNA, Viral/isolation & purification/metabolism ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/genetics/pathogenicity ; Thrombosis/metabolism/*physiopathology/virology ; Viral Tropism ; Post-Acute COVID-19 Syndrome ; }, abstract = {Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.}, } @article {pmid33537155, year = {2021}, author = {Al-Jahdhami, I and Al-Naamani, K and Al-Mawali, A}, title = {The Post-acute COVID-19 Syndrome (Long COVID).}, journal = {Oman medical journal}, volume = {36}, number = {1}, pages = {e220}, pmid = {33537155}, issn = {1999-768X}, } @article {pmid33532785, year = {2021}, author = {Lopez-Leon, S and Wegman-Ostrosky, T and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S}, title = {More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {33532785}, support = {R21 NS106640/NS/NINDS NIH HHS/United States ; }, abstract = {COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1[st] of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I[2] statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.}, } @article {pmid33528827, year = {2021}, author = {Simani, L and Ramezani, M and Darazam, IA and Sagharichi, M and Aalipour, MA and Ghorbani, F and Pakdaman, H}, title = {Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.}, journal = {Journal of neurovirology}, volume = {27}, number = {1}, pages = {154-159}, pmid = {33528827}, issn = {1538-2443}, mesh = {Adult ; Aged ; Antiviral Agents/therapeutic use ; COVID-19/complications/*psychology/virology ; Cough/complications/drug therapy/*psychology/virology ; Dementia/complications/drug therapy/*psychology/virology ; Drug Combinations ; Dyspnea/complications/drug therapy/*psychology/virology ; Fatigue Syndrome, Chronic/complications/drug therapy/*psychology/virology ; Female ; Fever/complications/drug therapy/*psychology/virology ; Humans ; Hydroxychloroquine/therapeutic use ; Lopinavir/therapeutic use ; Male ; Middle Aged ; Oseltamivir/therapeutic use ; Research Design ; Ritonavir/therapeutic use ; SARS-CoV-2/drug effects/pathogenicity ; Severity of Illness Index ; Stress Disorders, Post-Traumatic/complications/drug therapy/*psychology/virology ; Surveys and Questionnaires ; Survivors/psychology ; COVID-19 Drug Treatment ; }, abstract = {As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.}, } @article {pmid33519972, year = {2021}, author = {Lucas, S}, title = {Pandemics and pathology: a reflection on influenza, HIV/AIDS and SARS (COVID-19) pandemic infections.}, journal = {Diagnostic histopathology (Oxford, England)}, volume = {27}, number = {3}, pages = {128-133}, pmid = {33519972}, issn = {1756-2317}, abstract = {The COVID-19 pandemic has reminded pathologists of our significant roles in the management and understanding of rapidly spreading and dangerous pathogens, from identifying the agent to characterizing the clinical pathology to managing the dead. Cellular pathology - through autopsy - has depicted the main features: viral pneumonitis, acute lung injury, organising pneumonia, secondary bacterial pneumonia, thrombophilia and infarction, and systemic inflammatory response syndrome with multi-organ failure. These are similar to another viral pandemic of the 20th century, H1N1 influenza; but contrast with the second major more complicated pandemic, that of HIV/AIDS. The outcomes of these infections are compared, along with seasonal influenza and SARS-1-CoV disease. Work to be done on COVID-19 includes characterisation of the emerging 'long COVID' syndrome, and monitoring the complications of therapies and vaccination programs.}, } @article {pmid33509811, year = {2021}, author = {Atherton, H and Briggs, T and Chew-Graham, C}, title = {Long COVID and the importance of the doctor-patient relationship.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {71}, number = {703}, pages = {54-55}, pmid = {33509811}, issn = {1478-5242}, mesh = {*COVID-19/complications ; Humans ; *Physician-Patient Relations ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33501596, year = {2021}, author = {Becker, RC}, title = {COVID-19 and its sequelae: a platform for optimal patient care, discovery and training.}, journal = {Journal of thrombosis and thrombolysis}, volume = {51}, number = {3}, pages = {587-594}, pmid = {33501596}, issn = {1573-742X}, mesh = {*Aftercare ; COVID-19/*complications ; Chronic Disease ; Humans ; Survivors ; Post-Acute COVID-19 Syndrome ; }, abstract = {COVID-19- related patient care and research have focused on short-term outcomes, particularly among those with underlying or preexisting medical conditions. A major focus has been on mortality rates. Broadening the dialogue is neither meant nor intended to disparage the near-term devastation felt globally each day, but rather to begin preparation for optimally caring for and addressing the needs of survivors. The sequelae of COVID-19 includes acute, subacute and chronic stages of the condition. If one applies current World Health Organization (WHO) statistics to calculate the global burden of disease, there are 98,000,000 COVID-19 survivors. The following editorial focuses on post-COVID sequelae as a continuum of patient care needs, as well as discovery and training opportunities in an academic setting.}, } @article {pmid33501506, year = {2021}, author = {Guedj, E and Campion, JY and Dudouet, P and Kaphan, E and Bregeon, F and Tissot-Dupont, H and Guis, S and Barthelemy, F and Habert, P and Ceccaldi, M and Million, M and Raoult, D and Cammilleri, S and Eldin, C}, title = {[18]F-FDG brain PET hypometabolism in patients with long COVID.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {48}, number = {9}, pages = {2823-2833}, pmid = {33501506}, issn = {1619-7089}, support = {07/09//PHRC/ ; }, mesh = {Brain/diagnostic imaging ; *COVID-19/complications ; *Fluorodeoxyglucose F18 ; Humans ; Positron-Emission Tomography ; Retrospective Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {PURPOSE: In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of [18]F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection.

METHODS: PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints.

RESULTS: In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001).

CONCLUSION: This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.}, } @article {pmid33497594, year = {2021}, author = {Fekrazad, R and Fekrazad, S}, title = {The Potential Role of Photobiomodulation in Long COVID-19 Patients Rehabilitation.}, journal = {Photobiomodulation, photomedicine, and laser surgery}, volume = {39}, number = {4}, pages = {229-231}, doi = {10.1089/photob.2020.4984}, pmid = {33497594}, issn = {2578-5478}, mesh = {COVID-19/*radiotherapy ; Humans ; Low-Level Light Therapy/*methods ; Pneumonia, Viral/*radiotherapy/virology ; SARS-CoV-2 ; }, } @article {pmid33487628, year = {2021}, author = {Stefano, GB and Ptacek, R and Ptackova, H and Martin, A and Kream, RM}, title = {Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {27}, number = {}, pages = {e930886}, pmid = {33487628}, issn = {1643-3750}, mesh = {COVID-19/complications/*metabolism/physiopathology/psychology/transmission ; Cognitive Dysfunction/*metabolism/physiopathology/psychology ; Energy Metabolism ; *Health Behavior ; Humans ; Hypoxia, Brain/*metabolism/physiopathology/psychology ; Microbial Viability ; Mitochondria/*metabolism ; Neurons/*metabolism ; SARS-CoV-2/*physiology ; Viral Load ; Virus Replication ; Post-Acute COVID-19 Syndrome ; }, abstract = {Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.}, } @article {pmid33486531, year = {2021}, author = {Sher, L}, title = {Post-COVID syndrome and suicide risk.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {114}, number = {2}, pages = {95-98}, pmid = {33486531}, issn = {1460-2393}, mesh = {COVID-19/*complications/*physiopathology/psychology ; Delirium/etiology ; Fatigue/etiology ; Headache/etiology ; Humans ; Mental Disorders/*etiology/physiopathology/psychology ; *Severity of Illness Index ; *Suicidal Ideation ; Survivors/*psychology ; }, abstract = {A significant number of coronavirus disease SARS-CoV-2 (COVID-19) patients continue to have symptoms related to COVID-19 after the acute phase of illness. This post-COVID condition is sometimes called 'post-COVID syndrome', 'long COVID' or 'post-acute COVID-19'. Persistent psychiatric symptoms among COVID-19 survivors such as depression, anxiety, post-traumatic symptoms and cognitive impairment may be related to psychological factors and neurobiological injury. COVID-19 related neurological symptoms including anosmia, ageusia, dizziness, headache and seizures may persist for a long time after the acute COVID-19 illness. Many COVID-19 survivors experience persistent physical symptoms such as cough, fatigue, dyspnea and pain after recovering from their initial illness. There is a high probability that symptoms of psychiatric, neurological and physical illnesses, as well as inflammatory damage to the brain in individuals with post-COVID syndrome increase suicidal ideation and behavior in this patient population. COVID-19 survivors without post-COVID syndrome may also be at elevated suicide risk. Studies of suicidality in COVID-19 survivors are urgently needed and will be a new area of suicide research. An appropriate management of psychiatric, neurological and medical conditions may reduce suicide risk among COVID-19 survivors with or without post-COVID syndrome.}, } @article {pmid33479069, year = {2021}, author = {Ladds, E and Rushforth, A and Wieringa, S and Taylor, S and Rayner, C and Husain, L and Greenhalgh, T}, title = {Developing services for long COVID: lessons from a study of wounded healers.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {1}, pages = {59-65}, pmid = {33479069}, issn = {1473-4893}, mesh = {Adult ; COVID-19/*diagnosis/epidemiology/therapy ; Delivery of Health Care/*organization & administration ; Female ; Health Personnel/*statistics & numerical data ; Humans ; Male ; Middle Aged ; *Pandemics ; SARS-CoV-2 ; }, abstract = {Persistent symptoms lasting longer than 3 weeks are thought to affect 10-20% of patients following SARS-CoV-2 infection. No formal guidelines exist in the UK for treating patients with long COVID and services are sporadic and variable, although additional funding is promised for their development.In this study, narrative interviews and focus groups are used to explore the lived experience of 43 healthcare professionals with long COVID. These individuals see the healthcare system from both professional and patient perspectives, thus represent an important wealth of expertise to inform service design.We present a set of co-designed quality standards, highlighting equity and ease of access, minimal patient care burden, clinical responsibility, a multidisciplinary and evidence-based approach, and patient involvement; and we apply these to propose a potential care pathway model that could be adapted and translated to improve care of patients long COVID.}, } @article {pmid33468452, year = {2021}, author = {Simpson, FK and Lokugamage, AU}, title = {The elephant and the blind men: the children of long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {372}, number = {}, pages = {n157}, doi = {10.1136/bmj.n157}, pmid = {33468452}, issn = {1756-1833}, } @article {pmid33462068, year = {2021}, author = {Raahimi, MM and Kane, A and Moore, CE and Alareed, AW}, title = {Late onset of Guillain-Barré syndrome following SARS-CoV-2 infection: part of 'long COVID-19 syndrome'?.}, journal = {BMJ case reports}, volume = {14}, number = {1}, pages = {}, pmid = {33462068}, issn = {1757-790X}, mesh = {COVID-19/*complications/physiopathology ; Electrodiagnosis ; Guillain-Barre Syndrome/diagnosis/*physiopathology/therapy ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Late Onset Disorders ; Male ; Middle Aged ; Muscle Weakness/*physiopathology ; Neural Conduction ; Neuralgia/*physiopathology ; Noninvasive Ventilation ; Paresthesia/*physiopathology ; SARS-CoV-2 ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {We describe a case of delayed onset, acute demyelinating neuropathy secondary to novel SARS-CoV-2 infection. A previously healthy 46-year-old man presented with bilateral leg pain and loss of sensation in his feet 53 days after having COVID-19 pneumonitis. He developed painful sensory symptoms followed by a rapidly progressive lower motor neuron weakness involving all limbs, face and respiratory muscles, needing ventilatory support. In keeping with a diagnosis of Guillain-Barré syndrome, cerebrospinal fluid examination showed albuminocytologic dissociation and nerve conduction studies supported the diagnosis of an acute inflammatory demyelinating polyradiculoneuropathy. The delayed neurological dysfunction seen in our patient following SARS-CoV-2 infection may indicate a novel mechanism of disease that is part of the emerging 'long COVID-19 syndrome'.}, } @article {pmid33461632, year = {2021}, author = {Venturelli, S and Benatti, SV and Casati, M and Binda, F and Zuglian, G and Imeri, G and Conti, C and Biffi, AM and Spada, MS and Bondi, E and Camera, G and Severgnini, R and Giammarresi, A and Marinaro, C and Rossini, A and Bonaffini, PA and Guerra, G and Bellasi, A and Cesa, S and Rizzi, M}, title = {Surviving COVID-19 in Bergamo province: a post-acute outpatient re-evaluation.}, journal = {Epidemiology and infection}, volume = {149}, number = {}, pages = {e32}, pmid = {33461632}, issn = {1469-4409}, mesh = {Adult ; Aftercare ; Aged ; Aged, 80 and over ; COVID-19/complications/*mortality/*pathology ; Female ; Hospitalization ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Patient Discharge ; Polymerase Chain Reaction ; RNA, Viral/blood ; *SARS-CoV-2 ; Severity of Illness Index ; Young Adult ; }, abstract = {Bergamo province was badly hit by the coronavirus disease 2019 (COVID-19) epidemic. We organised a public-funded, multidisciplinary follow-up programme for COVID-19 patients discharged from the emergency department or from the inpatient wards of 'Papa Giovanni XXIII' Hospital, the largest public hospital in the area. As of 31 July, the first 767 patients had completed the first post-discharge multidisciplinary assessment. Patients entered our programme at a median time of 81 days after discharge. Among them, 51.4% still complained of symptoms, most commonly fatigue and exertional dyspnoea, and 30.5% were still experiencing post-traumatic psychological consequences. Impaired lung diffusion was found in 19%. Seventeen per cent had D-dimer values two times above the threshold for diagnosis of pulmonary embolism (two unexpected and clinically silent pulmonary thrombosis were discovered by investigating striking D-dimer elevation). Survivors of COVID-19 exhibit a complex array of symptoms, whose common underlying pathology, if any, has still to be elucidated: a multidisciplinary approach is fundamental, to address the different problems and to look for effective solutions.}, } @article {pmid33460566, year = {2021}, author = {McMahon, DE and Gallman, AE and Hruza, GJ and Rosenbach, M and Lipoff, JB and Desai, SR and French, LE and Lim, H and Cyster, JG and Fox, LP and Fassett, MS and Freeman, EE}, title = {Long COVID in the skin: a registry analysis of COVID-19 dermatological duration.}, journal = {The Lancet. Infectious diseases}, volume = {21}, number = {3}, pages = {313-314}, pmid = {33460566}, issn = {1474-4457}, support = {T32 GM007618/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; COVID-19/*diagnosis/immunology/pathology/virology ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2/*isolation & purification ; Skin/*virology ; Skin Diseases/*diagnosis/immunology/pathology/*virology ; Young Adult ; }, } @article {pmid33459404, year = {2021}, author = {Ludvigsson, JF}, title = {Reporting suspicions of long COVID in children is justified during this global emergency.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {4}, pages = {1373}, pmid = {33459404}, issn = {1651-2227}, mesh = {Adult ; *COVID-19 ; Child ; Emergency Service, Hospital ; Humans ; SARS-CoV-2 ; }, } @article {pmid33458558, year = {2021}, author = {McFarland, AJ and Yousuf, MS and Shiers, S and Price, TJ}, title = {Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain.}, journal = {Pain reports}, volume = {6}, number = {1}, pages = {e885}, pmid = {33458558}, issn = {2471-2531}, abstract = {SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease. There is now strong evidence for neurological impacts of COVID-19, with pain as an important symptom, both in the acute phase of the disease and at later stages that are colloquially referred to as "long COVID." In this narrative review, we discuss how COVID-19 may interact with the peripheral nervous system to cause pain in the early and late stages of the disease. We begin with a review of the state of the science on how viruses cause pain through direct and indirect interactions with nociceptors. We then cover what we currently know about how the unique cytokine profiles of moderate and severe COVID-19 may drive plasticity in nociceptors to promote pain and worsen existing pain states. Finally, we review evidence for direct infection of nociceptors by SARS-CoV-2 and the implications of this potential neurotropism. The state of the science points to multiple potential mechanisms through which COVID-19 could induce changes in nociceptor excitability that would be expected to promote pain, induce neuropathies, and worsen existing pain states.}, } @article {pmid33453162, year = {2021}, author = {Venkatesan, P}, title = {NICE guideline on long COVID.}, journal = {The Lancet. Respiratory medicine}, volume = {9}, number = {2}, pages = {129}, doi = {10.1016/S2213-2600(21)00031-X}, pmid = {33453162}, issn = {2213-2619}, mesh = {Humans ; *Cognitive Dysfunction/etiology/physiopathology ; *COVID-19/complications/physiopathology/rehabilitation ; *Fatigue/etiology/physiopathology ; *Heart Diseases/etiology/physiopathology ; *Lung/physiopathology ; SARS-CoV-2 ; Time ; United Kingdom ; Practice Guidelines as Topic ; }, } @article {pmid33391730, year = {2020}, author = {Doykov, I and Hällqvist, J and Gilmour, KC and Grandjean, L and Mills, K and Heywood, WE}, title = {'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {1349}, pmid = {33391730}, issn = {2046-1402}, mesh = {COVID-19/*complications/*diagnosis ; Humans ; Inflammation/*virology ; Mass Spectrometry ; Post-Acute COVID-19 Syndrome ; }, abstract = {'Long Covid', or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.}, } @article {pmid33442016, year = {2021}, author = {Brodin, P}, title = {Immune determinants of COVID-19 disease presentation and severity.}, journal = {Nature medicine}, volume = {27}, number = {1}, pages = {28-33}, pmid = {33442016}, issn = {1546-170X}, mesh = {Adaptive Immunity ; Adult ; Age Factors ; Aged ; COVID-19/complications/epidemiology/etiology/*immunology/*physiopathology ; Child ; Female ; Humans ; Immunity, Innate ; Immunologic Deficiency Syndromes/chemically induced/immunology/virology ; Male ; SARS-CoV-2/immunology/*physiology ; Severity of Illness Index ; Sex Factors ; Systemic Inflammatory Response Syndrome/etiology ; Virus Internalization ; }, abstract = {COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such 'long COVID' is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.}, } @article {pmid33403997, year = {2020}, author = {Mendelson, M and Nel, J and Blumberg, L and Madhi, SA and Dryden, M and Stevens, W and Venter, FWD}, title = {Long-COVID: An evolving problem with an extensive impact.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {111}, number = {1}, pages = {10-12}, doi = {10.7196/SAMJ.2020.v111i11.15433}, pmid = {33403997}, issn = {2078-5135}, mesh = {Age Factors ; Anosmia/physiopathology ; COVID-19/*complications/epidemiology/physiopathology/therapy ; Cognitive Dysfunction/physiopathology ; Comorbidity ; Dyspnea/physiopathology ; Fatigue/physiopathology ; Headache/physiopathology ; *Health Planning ; Humans ; Obesity/epidemiology ; *Physical and Rehabilitation Medicine ; *Primary Health Care ; Recovery of Function ; Risk Assessment ; SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; South Africa ; Time Factors ; Post-Acute COVID-19 Syndrome ; }, abstract = {Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. 'Long-COVID' or 'COVID long-haulers' generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.}, } @article {pmid33403218, year = {2020}, author = {Amenta, EM and Spallone, A and Rodriguez-Barradas, MC and El Sahly, HM and Atmar, RL and Kulkarni, PA}, title = {Postacute COVID-19: An Overview and Approach to Classification.}, journal = {Open forum infectious diseases}, volume = {7}, number = {12}, pages = {ofaa509}, pmid = {33403218}, issn = {2328-8957}, support = {T32 AI055413/AI/NIAID NIH HHS/United States ; }, abstract = {As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.}, } @article {pmid33401287, year = {2020}, author = {Soriano, V and Ganado-Pinilla, P and Sánchez-Santos, M and Barreiro, P}, title = {Unveiling Long COVID-19 Disease.}, journal = {AIDS reviews}, volume = {22}, number = {4}, pages = {227-228}, doi = {10.24875/AIDSRev.M20000039}, pmid = {33401287}, issn = {1698-6997}, mesh = {COVID-19/*virology ; HIV-1/genetics/pathogenicity ; Hepatitis B virus/genetics/pathogenicity ; Humans ; SARS-CoV-2/*genetics/*pathogenicity ; }, abstract = {The clinical spectrum of "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) infection is wider than initially thought. The coronavirus does not establish a chronic cellular infection, in contrast with HIV or the hepatitis B virus, that keeps their genomes, respectively, as proviruses integrated within the chromosomes or as episomes (Soriano et al. J Antimicrob Chemother 2014).}, } @article {pmid33398279, year = {2020}, author = {Lever, J and Altman, RB}, title = {Analyzing the vast coronavirus literature with CoronaCentral.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {33398279}, issn = {2692-8205}, support = {R01 LM005652/LM/NLM NIH HHS/United States ; }, abstract = {The global SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming rate of publications means that human researchers are unable to keep abreast of the research. To ameliorate this, we present the CoronaCentral resource which uses machine learning to process the research literature on SARS-CoV-2 along with articles on SARS-CoV and MERS-CoV. We break the literature down into useful categories and enable analysis of the contents, pace, and emphasis of research during the crisis. These categories cover therapeutics, forecasting as well as growing areas such as "Long Covid" and studies of inequality and misinformation. Using this data, we compare topics that appear in original research articles compared to commentaries and other article types. Finally, using Altmetric data, we identify the topics that have gained the most media attention. This resource, available at https://coronacentral.ai , is updated multiple times per day and provides an easy-to-navigate system to find papers in different categories, focussing on different aspects of the virus along with currently trending articles.}, } @article {pmid33398216, year = {2021}, author = {van Dijk, F}, title = {[Not Available].}, journal = {Tijdschrift voor bedrijfs- en verzekeringsgeneeskunde}, volume = {29}, number = {1}, pages = {26-30}, doi = {10.1007/s12498-020-1322-x}, pmid = {33398216}, issn = {1876-5858}, } @article {pmid33391622, year = {2020}, author = {Nhamo, G and Kandawasvika, GQ and Sibanda, M}, title = {Non-pharmaceutical strategies win coronavirus disease 2019 battle in New Zealand.}, journal = {Jamba (Potchefstroom, South Africa)}, volume = {12}, number = {1}, pages = {1010}, pmid = {33391622}, issn = {1996-1421}, abstract = {This literature-based article found that on 08 June 2020, New Zealand claimed victory over coronavirus disease 2019 (COVID-19) mainly because of effective non-pharmaceutical strategies and interventions that included a hard lockdown. The response was informed by the country's Influenza Pandemic Plan (although without criticism), which was updated in 2017, and the swift responses from political leadership and other key stakeholders. Strategies instituted included the proclamation of urgent precautionary measures leading to border closures, issuing of a 3-month-long COVID-19 notice under the Epidemic Preparedness Act 2006, the proclamation of the COVID-19 Elimination Strategy and the Initial COVID-19 Māori Response Action Plan, which incorporated COVID-19 Alert Levels that facilitated stepwise easing of the hard lockdown. The non-pharmaceutical strategies seem to have worked again, even as the second wave of COVID-19 infections returned in August 2020 through an Auckland cluster. Hence, the New Zealand case remains one that the world can draw lessons from, although not perfect.}, } @article {pmid33361141, year = {2020}, author = {Sivan, M and Taylor, S}, title = {NICE guideline on long covid.}, journal = {BMJ (Clinical research ed.)}, volume = {371}, number = {}, pages = {m4938}, doi = {10.1136/bmj.m4938}, pmid = {33361141}, issn = {1756-1833}, mesh = {COVID-19/complications/diagnosis/*therapy ; General Practitioners/standards ; Guideline Adherence/standards ; Humans ; *Practice Guidelines as Topic ; Practice Patterns, Physicians'/*standards ; Scotland ; Time Factors ; }, } @article {pmid33357467, year = {2021}, author = {Gorna, R and MacDermott, N and Rayner, C and O'Hara, M and Evans, S and Agyen, L and Nutland, W and Rogers, N and Hastie, C}, title = {Long COVID guidelines need to reflect lived experience.}, journal = {Lancet (London, England)}, volume = {397}, number = {10273}, pages = {455-457}, pmid = {33357467}, issn = {1474-547X}, mesh = {COVID-19/*complications/epidemiology ; *Guidelines as Topic ; Humans ; Qualitative Research ; SARS-CoV-2 ; *Symptom Assessment ; Time Factors ; }, } @article {pmid33347790, year = {2021}, author = {Higgins, V and Sohaei, D and Diamandis, EP and Prassas, I}, title = {COVID-19: from an acute to chronic disease? Potential long-term health consequences.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {58}, number = {5}, pages = {297-310}, doi = {10.1080/10408363.2020.1860895}, pmid = {33347790}, issn = {1549-781X}, mesh = {Betacoronavirus ; COVID-19/*complications ; *Chronic Disease ; Coronavirus Infections ; Critical Illness ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite pulmonary impairments being the most prevalent, extra-pulmonary manifestations of COVID-19 are abundant. Confirmed COVID-19 cases have now surpassed 57.8 million worldwide as of 22 November 2020. With estimated case fatality rates (number of deaths from COVID-19 divided by number of confirmed COVID-19 cases) varying between 1 and 7%, there will be a large population of recovered COVID-19 patients that may acquire a multitude of long-term health consequences. While the multi-organ manifestations of COVID-19 are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. In this review, we turn to previous similar coronaviruses (i.e. SARS-CoV-1 and Middle East respiratory syndrome coronavirus [MERS-CoV]) in combination with known health implications of SARS-CoV-2 infection to predict potential long-term effects of COVID-19, including pulmonary, cardiovascular, hematologic, renal, central nervous system, gastrointestinal, and psychosocial manifestations, in addition to the well-known post-intensive care syndrome. It is necessary to monitor COVID-19 patients after discharge to understand the breadth and severity of long-term effects. This can be accomplished by repurposing or initiating large cohort studies to not only focus on the long-term consequences of SARS-CoV-2 infection, but also on acquired immune function as well as ethno-racial group and household income disparities in COVID-19 cases and hospitalizations. The future for COVID-19 survivors remains uncertain, and if this virus circulates among us for years to come, long-term effects may accumulate exponentially.}, } @article {pmid33342437, year = {2020}, author = {Ladds, E and Rushforth, A and Wieringa, S and Taylor, S and Rayner, C and Husain, L and Greenhalgh, T}, title = {Persistent symptoms after Covid-19: qualitative study of 114 "long Covid" patients and draft quality principles for services.}, journal = {BMC health services research}, volume = {20}, number = {1}, pages = {1144}, pmid = {33342437}, issn = {1472-6963}, support = {/WT_/Wellcome Trust/United Kingdom ; WT104830MA/WT_/Wellcome Trust/United Kingdom ; BRC-1215-20008//National Institute for Health Research/ ; ES/V010069/1//Economic and Social Research Council/ ; }, mesh = {Adult ; Aged ; COVID-19/*complications/*therapy ; Female ; Focus Groups ; Health Personnel/psychology/statistics & numerical data ; Health Services Research ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Qualitative Research ; Quality of Health Care/organization & administration ; Time Factors ; United Kingdom ; }, abstract = {BACKGROUND: Approximately 10% of patients with Covid-19 experience symptoms beyond 3-4 weeks. Patients call this "long Covid". We sought to document such patients' lived experience, including accessing and receiving healthcare and ideas for improving services.

METHODS: We held 55 individual interviews and 8 focus groups (n = 59) with people recruited from UK-based long Covid patient support groups, social media and snowballing. We restricted some focus groups to health professionals since they had already self-organised into online communities. Participants were invited to tell their stories and comment on others' stories. Data were audiotaped, transcribed, anonymised and coded using NVIVO. Analysis incorporated sociological theories of illness, healing, peer support, clinical relationships, access, and service redesign.

RESULTS: Of 114 participants aged 27-73 years, 80 were female. Eighty-four were White British, 13 Asian, 8 White Other, 5 Black, and 4 mixed ethnicity. Thirty-two were doctors and 19 other health professionals. Thirty-one had attended hospital, of whom 8 had been admitted. Analysis revealed a confusing illness with many, varied and often relapsing-remitting symptoms and uncertain prognosis; a heavy sense of loss and stigma; difficulty accessing and navigating services; difficulty being taken seriously and achieving a diagnosis; disjointed and siloed care (including inability to access specialist services); variation in standards (e.g. inconsistent criteria for seeing, investigating and referring patients); variable quality of the therapeutic relationship (some participants felt well supported while others felt "fobbed off"); and possible critical events (e.g. deterioration after being unable to access services). Emotionally significant aspects of participants' experiences informed ideas for improving services.

CONCLUSION: Suggested quality principles for a long Covid service include ensuring access to care, reducing burden of illness, taking clinical responsibility and providing continuity of care, multi-disciplinary rehabilitation, evidence-based investigation and management, and further development of the knowledge base and clinical services.

TRIAL REGISTRATION: NCT04435041.}, } @article {pmid33341598, year = {2021}, author = {Raveendran, AV}, title = {Long COVID-19: Challenges in the diagnosis and proposed diagnostic criteria.}, journal = {Diabetes & metabolic syndrome}, volume = {15}, number = {1}, pages = {145-146}, pmid = {33341598}, issn = {1878-0334}, mesh = {COVID-19/*complications/diagnosis/epidemiology ; COVID-19 Testing/*methods ; Humans ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33329145, year = {2020}, author = {Metastasio, A and Prevete, E and Singh, D and Grundmann, O and Prozialeck, WC and Veltri, C and Bersani, G and Corazza, O}, title = {Can Kratom (Mitragyna speciosa) Alleviate COVID-19 Pain? A Case Study.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {594816}, pmid = {33329145}, issn = {1664-0640}, abstract = {Among the symptoms of COVID-19 fever, general malaise, pain and aches, myalgia, fatigue, and headache can affect the quality of life of patients, even after the end of the acute phase of the infection and can be long lasting. The current treatment of these symptoms, also because COVID-19 patients have been asked not to use non-steroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen are often unsatisfactory. Among the above mentioned symptoms malaise and fatigue seem the most difficult to treat. In this case report we describe the use of kratom (Mitragyna speciosa) by a patient with confirmed COVID-19 infection. What we observed was a fast and sustained relieve of the above mentioned symptoms.}, } @article {pmid33322316, year = {2020}, author = {Vink, M and Vink-Niese, A}, title = {Could Cognitive Behavioural Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome? Lessons from the Qure Study for Q-Fever Fatigue Syndrome.}, journal = {Healthcare (Basel, Switzerland)}, volume = {8}, number = {4}, pages = {}, pmid = {33322316}, issn = {2227-9032}, abstract = {An increasing number of young and previously fit and healthy people who did not require hospitalisation continue to have symptoms months after mild cases of COVID-19. Rehabilitation clinics are already offering cognitive behavioural therapy (CBT) as an effective treatment for long COVID and post-COVID-19 fatigue syndrome based on the claims that it is effective for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-the most common post-infectious syndrome-as no study into the efficacy of CBT for post-COVID-19 fatigue syndrome has been published. Re-analyses of these studies, however, showed that CBT did not lead to objective improvements in heterogeneous groups of ME/CFS patients, nor did it restore the ability to work. The group of patients with long COVID and post-COVID-19 fatigue syndrome, on the other hand, is homogeneous. We therefore analysed the Dutch Qure study, as it studied the efficacy of CBT in a homogeneous group of patients who developed Q-fever fatigue syndrome-which affects up to 30% of patients-after the largest reported outbreak of Q-fever, to see if CBT might potentially be an effective treatment for long-haulers after COVID-19 infection. Our reanalysis found that the Qure study suffered from many serious methodological problems, which included relying on one subjective primary outcome in a study without a control group for the non-blinded CBT treatment group, using a post hoc definition of improvement, waiting 2 years before publishing their objective actometer results and ignoring the null effect of said results. Moreover, only 10% of participants achieved a clinically meaningful subjective improvement in fatigue as a result of CBT according to the study's own figures. Consequently, CBT has no subjective clinically meaningful effect in nine out of every ten patients that are treated with it. Additionally, the subjective improvement in fatigue was not matched by an improvement in disability, even though the disability was fatigue related according to the researchers. On top of this, CBT did not lead to an objective improvement in physical performance. Therefore, it cannot be said that CBT is an effective treatment for Q-fever fatigue syndrome either. It seems therefore unlikely that CBT will reduce disability or lead to objective improvement in long COVID or in post-COVID-19 fatigue syndrome.}, } @article {pmid33320511, year = {2020}, author = {Greenhalgh, T and Knight, M}, title = {Long COVID: A Primer for Family Physicians.}, journal = {American family physician}, volume = {102}, number = {12}, pages = {716-717}, pmid = {33320511}, issn = {1532-0650}, mesh = {*Attitude of Health Personnel ; COVID-19/*therapy ; COVID-19 Testing/statistics & numerical data ; Family Practice/*organization & administration ; Humans ; *Physician-Patient Relations ; Primary Health Care/*organization & administration ; Telemedicine/organization & administration ; }, } @article {pmid33316400, year = {2021}, author = {Yelin, D and Margalit, I and Yahav, D and Runold, M and Bruchfeld, J}, title = {Long COVID-19-it's not over until?.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {4}, pages = {506-508}, pmid = {33316400}, issn = {1469-0691}, mesh = {COVID-19/*complications/epidemiology/etiology/physiopathology ; Cohort Studies ; Humans ; Morbidity ; Recovery of Function ; *Survivors ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33310813, year = {2020}, author = {Das, S and Rasul, MG and Hossain, MS and Khan, AR and Alam, MA and Ahmed, T and Clemens, JD}, title = {Acute food insecurity and short-term coping strategies of urban and rural households of Bangladesh during the lockdown period of COVID-19 pandemic of 2020: report of a cross-sectional survey.}, journal = {BMJ open}, volume = {10}, number = {12}, pages = {e043365}, pmid = {33310813}, issn = {2044-6055}, mesh = {*Adaptation, Psychological ; Bangladesh/epidemiology ; COVID-19/*epidemiology ; Cross-Sectional Studies ; Family Characteristics ; Female ; *Food Insecurity ; Humans ; Male ; Nutrition Surveys ; *Physical Distancing ; Rural Population/statistics & numerical data ; Socioeconomic Factors ; Urban Population/statistics & numerical data ; }, abstract = {INTRODUCTION: We conducted a cross-sectional survey to assess the extent and to identify the determinants of food insecurity and coping strategies in urban and rural households of Bangladesh during the month-long, COVID-19 lockdown period.

SETTING: Selected urban and rural areas of Bangladesh.

PARTICIPANTS: 106 urban and 106 rural households.

OUTCOME VARIABLES AND METHOD: Household food insecurity status and the types of coping strategies were the outcome variables for the analyses. Multinomial logistic regression analyses were done to identify the determinants.

RESULTS: We found that around 90% of the households were suffering from different grades of food insecurity. Severe food insecurity was higher in urban (42%) than rural (15%) households. The rural households with mild/moderate food insecurity adopted either financial (27%) or both financial and food compromised (32%) coping strategies, but 61% of urban mild/moderate food insecure households applied both forms of coping strategies. Similarly, nearly 90% of severely food insecure households implemented both types of coping strategies. Living in poorest households was significantly associated (p value <0.05) with mild/moderate (regression coefficient, β: 15.13, 95% CI 14.43 to 15.82), and severe food insecurity (β: 16.28, 95% CI 15.58 to 16.97). The statistically significant (p <0.05) determinants of both food compromised and financial coping strategies were living in urban areas (β: 1.8, 95% CI 0.44 to 3.09), living in poorest (β: 2.7, 95% CI 1 to 4.45), poorer (β: 2.6, 95% CI 0.75 to 4.4) and even in the richer (β: 1.6, 95% CI 0.2 to 2.9) households and age of the respondent (β: 0.1, 95% CI 0.02 to 0.21).

CONCLUSION: Both urban and rural households suffered from moderate to severe food insecurity during the month-long lockdown period in Bangladesh. But, poorest, poorer and even the richer households adopted different coping strategies that might result in long-term economic and nutritional consequences.}, } @article {pmid33308453, year = {2020}, author = {The Lancet, }, title = {Facing up to long COVID.}, journal = {Lancet (London, England)}, volume = {396}, number = {10266}, pages = {1861}, doi = {10.1016/S0140-6736(20)32662-3}, pmid = {33308453}, issn = {1474-547X}, mesh = {COVID-19/*complications/epidemiology ; Humans ; SARS-CoV-2/isolation & purification ; *Symptom Assessment ; Time Factors ; }, } @article {pmid33288947, year = {2020}, author = {}, title = {Meeting the challenge of long COVID.}, journal = {Nature medicine}, volume = {26}, number = {12}, pages = {1803}, doi = {10.1038/s41591-020-01177-6}, pmid = {33288947}, issn = {1546-170X}, mesh = {COVID-19/*epidemiology/therapy/virology ; Humans ; *Pandemics ; SARS-CoV-2/*pathogenicity ; }, } @article {pmid33269366, year = {2020}, author = {Walsh-Messinger, J and Manis, H and Vrabec, A and Sizemore, J and Bishof, K and Debidda, M and Malaspina, D and Greenspan, N}, title = {The Kids Are Not Alright: A Preliminary Report of Post-COVID Syndrome in University Students.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {33269366}, support = {R01 MH110418/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: Post-COVID syndrome is increasingly recognized by the medical community but has not been studied exclusively in young adults. This preliminary report investigates the prevalence and features of protracted symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness.

METHODS: 148 students completed an online study to earn research credit for class. Data from COVID-19 positive participants with symptoms ≥28 days (N=22) were compared to those who fully recovered (N=21) and those not diagnosed with COVID-19 (N=58).

RESULTS: 51% of participants who contracted COVID-19 (N=43) experienced symptoms ≥28 days and were classified as having post-COVID syndrome; all but one (96%) were female. During acute illness the post-COVID group, compared to those who fully recovered, experienced significantly more chest pain (64% vs 14%; P=.002), fatigue (86% vs 48%; P=.009), fever (82% vs 48%; P=.02), olfactory impairment (82% vs 52%; P=.04), headaches (32% vs 5%; P<.05), and diarrhea (32% vs 5%; P<.05). Compared to those not diagnosed with COVID-19, the post-COVID syndrome group more frequently experienced exercise intolerance (43% vs. 0%; P<.001), dyspnea (43% vs. 0%; P<.001), chest pain (31% vs 7%; P=.002), olfactory impairment (19% vs 0%; P=.004), lymphadenopathy (19% vs 0%; P=.004), gustatory impairment (14% vs 0%; P=.02), and appetite loss (36% vs 14%; P=.02).

INTERPRETATION: Our results contradict the perception that this "yet to be defined" post-COVID syndrome predominantly affects middle-aged adults and suggest that exercise intolerance, dyspnea, chest pain, chemosensory impairment, lymphadenopathy, rhinitis, and appetite loss may differentiate post-COVID syndrome from general symptoms of pandemic, age, and academic related stress. These findings are also consistent with previous reports that females are more vulnerable to this post viral syndrome. Large-scale population-based studies are essential to discerning the magnitude and characterization of post-COVID syndrome in young adults as well as more diverse populations.}, } @article {pmid33268328, year = {2020}, author = {Lokugamage, AU and Bowen, MA and Blair, J}, title = {Long covid: doctors must assess and investigate patients properly.}, journal = {BMJ (Clinical research ed.)}, volume = {371}, number = {}, pages = {m4583}, doi = {10.1136/bmj.m4583}, pmid = {33268328}, issn = {1756-1833}, mesh = {*COVID-19/diagnosis ; Humans ; Pandemics ; *Physicians ; SARS-CoV-2 ; }, } @article {pmid33252665, year = {2021}, author = {Petersen, MS and Kristiansen, MF and Hanusson, KD and Danielsen, ME and Á Steig, B and Gaini, S and Strøm, M and Weihe, P}, title = {Long COVID in the Faroe Islands: A Longitudinal Study Among Nonhospitalized Patients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {73}, number = {11}, pages = {e4058-e4063}, doi = {10.1093/cid/ciaa1792}, pmid = {33252665}, issn = {1537-6591}, support = {//Cooperation's p/f Krúnborg and Bortartún/ ; }, mesh = {*COVID-19/complications ; Fatigue ; Humans ; Longitudinal Studies ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; }, abstract = {BACKGROUND: Little is known about long-term recovery from coronavirus disease 2019 (COVID-19) disease, especially in nonhospitalized individuals. In this longitudinal study we present symptoms registered during the acute phase as well as long COVID (ie, long-lasting COVID-19 symptoms) in patients from the Faroe Islands.

METHODS: All consecutive patients with confirmed reverse transcription-polymerase chain reaction testing from April to June 2020 were invited to participate in this study for the assessment of long COVID. Demographic and clinical characteristics and self-reported acute and persistent symptoms were assessed using a standardized detailed questionnaire administered at enrollment and at repeated phone interviews in the period 22 April to 16 August.

RESULTS: Of the 180 participants (96.3% of the 187 eligible COVID-19 patients), 53.1% reported persistence of at least 1 symptom after a mean of 125 days after symptoms onset, 33.0% reported 1 or 2 symptoms, and 20.1% reported 3 or more symptoms. At the last follow-up, 46.9% were asymptomatic compared with 4.4% during the acute phase. The most prevalent persistent symptoms were fatigue, loss of smell and taste, and arthralgias.

CONCLUSIONS: Our results show that it might take months for symptoms to resolve, even among nonhospitalized persons with mild illness course in the acute phase. Continued monitoring for long COVID is needed.}, } @article {pmid33243911, year = {2020}, author = {Rashid, A}, title = {Yonder: Long Covid, mental health video consultations, overactive bladder syndrome, and haematological malignancies.}, journal = {The British journal of general practice : the journal of the Royal College of General Practitioners}, volume = {70}, number = {701}, pages = {601}, pmid = {33243911}, issn = {1478-5242}, } @article {pmid33243837, year = {2021}, author = {Dani, M and Dirksen, A and Taraborrelli, P and Torocastro, M and Panagopoulos, D and Sutton, R and Lim, PB}, title = {Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.}, journal = {Clinical medicine (London, England)}, volume = {21}, number = {1}, pages = {e63-e67}, pmid = {33243837}, issn = {1473-4893}, mesh = {COVID-19/*epidemiology/therapy ; *Disease Management ; Global Health ; Humans ; Morbidity/trends ; *Pandemics ; *SARS-CoV-2 ; Survival Rate/trends ; }, abstract = {The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.}, } @article {pmid33205450, year = {2021}, author = {Ludvigsson, JF}, title = {Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {3}, pages = {914-921}, pmid = {33205450}, issn = {1651-2227}, mesh = {Adolescent ; Age Factors ; COVID-19/*complications/diagnosis/epidemiology ; Child ; Female ; Humans ; Male ; Symptom Assessment ; Time Factors ; }, abstract = {AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce.

METHODS: This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020.

RESULTS: The five children with potential long COVID had a median age of 12 years (range 9-15) and four were girls. They had symptoms for 6-8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children.

CONCLUSION: Children may experience similar long COVID symptoms to adults and females may be more affected.}, } @article {pmid33199035, year = {2021}, author = {Callard, F and Perego, E}, title = {How and why patients made Long Covid.}, journal = {Social science & medicine (1982)}, volume = {268}, number = {}, pages = {113426}, pmid = {33199035}, issn = {1873-5347}, support = {209513/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {COVID-19/epidemiology/*therapy ; Chronic Disease ; Humans ; Patients/*psychology ; *Terminology as Topic ; United Kingdom/epidemiology ; United States/epidemiology ; }, abstract = {Patients collectively made Long Covid - and cognate term 'Long-haul Covid' - in the first months of the pandemic. Patients, many with initially 'mild' illness, used various kinds of evidence and advocacy to demonstrate a longer, more complex course of illness than laid out in initial reports from Wuhan. Long Covid has a strong claim to be the first illness created through patients finding one another on Twitter: it moved from patients, through various media, to formal clinical and policy channels in just a few months. This initial mapping of Long Covid - by two patients with this illness - focuses on actors in the UK and USA and demonstrates how patients marshalled epistemic authority. Patient knowledge needs to be incorporated into how COVID-19 is conceptualised, researched, and treated.}, } @article {pmid33173222, year = {2020}, author = {White, P}, title = {Long COVID: don't consign ME/CFS to history.}, journal = {Nature}, volume = {587}, number = {7833}, pages = {197}, doi = {10.1038/d41586-020-03136-0}, pmid = {33173222}, issn = {1476-4687}, mesh = {Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; *Fatigue Syndrome, Chronic ; Humans ; *Pandemics ; *Pneumonia, Viral ; SARS-CoV-2 ; }, } @article {pmid33172844, year = {2021}, author = {Mandal, S and Barnett, J and Brill, SE and Brown, JS and Denneny, EK and Hare, SS and Heightman, M and Hillman, TE and Jacob, J and Jarvis, HC and Lipman, MCI and Naidu, SB and Nair, A and Porter, JC and Tomlinson, GS and Hurst, JR and , }, title = {'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19.}, journal = {Thorax}, volume = {76}, number = {4}, pages = {396-398}, pmid = {33172844}, issn = {1468-3296}, support = {/WT_/Wellcome Trust/United Kingdom ; 209553/WT_/Wellcome Trust/United Kingdom ; MR/N007727/1/MRC_/Medical Research Council/United Kingdom ; 209553/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Biomarkers/blood ; COVID-19/blood/*diagnosis ; Cross-Sectional Studies ; *Diagnostic Imaging ; Female ; Hospitalization/trends ; Humans ; Lung/*diagnostic imaging ; Male ; Middle Aged ; *Pandemics ; *SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.}, } @article {pmid33167766, year = {2020}, author = {Ashton, J}, title = {Long COVID - What doesn't kill you may not make you stronger.}, journal = {Journal of the Royal Society of Medicine}, volume = {113}, number = {11}, pages = {466-467}, pmid = {33167766}, issn = {1758-1095}, mesh = {*COVID-19/complications/epidemiology/mortality/prevention & control ; Chronic Disease ; *Dissent and Disputes ; Humans ; Immunity, Herd ; *Pandemics ; *Politics ; *Public Health ; }, } @article {pmid33123760, year = {2021}, author = {Sollini, M and Ciccarelli, M and Cecconi, M and Aghemo, A and Morelli, P and Gelardi, F and Chiti, A}, title = {Vasculitis changes in COVID-19 survivors with persistent symptoms: an [[18]F]FDG-PET/CT study.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {48}, number = {5}, pages = {1460-1466}, pmid = {33123760}, issn = {1619-7089}, mesh = {Adult ; Aged ; Aged, 80 and over ; *COVID-19 ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; SARS-CoV-2 ; Survivors ; *Vasculitis ; }, abstract = {PURPOSE: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[[18]F]fluoro-D-glucose ([[18]F]FDG) was able to demonstrate a persistent inflammatory process.

METHODS: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [[18]F]FDG positron emission tomography/computed tomography ([[18]F]FDG-PET/CT). Whole-body [[18]F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [[18]F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses.

RESULTS: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46-80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [[18]F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [[18]F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls.

CONCLUSION: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.}, } @article {pmid33095459, year = {2021}, author = {Baig, AM}, title = {Chronic COVID syndrome: Need for an appropriate medical terminology for long-COVID and COVID long-haulers.}, journal = {Journal of medical virology}, volume = {93}, number = {5}, pages = {2555-2556}, doi = {10.1002/jmv.26624}, pmid = {33095459}, issn = {1096-9071}, mesh = {COVID-19/*complications/diagnosis/physiopathology/virology ; Humans ; SARS-CoV-2/*physiology ; *Terminology as Topic ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33055076, year = {2020}, author = {Mahase, E}, title = {Long covid could be four different syndromes, review suggests.}, journal = {BMJ (Clinical research ed.)}, volume = {371}, number = {}, pages = {m3981}, doi = {10.1136/bmj.m3981}, pmid = {33055076}, issn = {1756-1833}, } @article {pmid33051223, year = {2020}, author = {Kingstone, T and Taylor, AK and O'Donnell, CA and Atherton, H and Blane, DN and Chew-Graham, CA}, title = {Finding the 'right' GP: a qualitative study of the experiences of people with long-COVID.}, journal = {BJGP open}, volume = {4}, number = {5}, pages = {}, pmid = {33051223}, issn = {2398-3795}, abstract = {BACKGROUND: An unknown proportion of people who had an apparently mild COVID-19 infection continue to suffer with persistent symptoms, including chest pain, shortness of breath, muscle and joint pains, headaches, cognitive impairment ('brain fog'), and fatigue. Post-acute COVID-19 ('long-COVID') seems to be a multisystem disease, sometimes occurring after a mild acute illness; people struggling with these persistent symptoms refer to themselves as 'long haulers'.

AIM: To explore experiences of people with persisting symptoms following COVID-19 infection, and their views on primary care support received.

DESIGN & SETTING: Qualitative methodology, with semi-structured interviews to explore perspectives of people with persisting symptoms following suspected or confirmed COVID-19 infection. Participants were recruited via social media between July-August 2020.

METHOD: Interviews were conducted by telephone or video call, digitally recorded, and transcribed with consent. Thematic analysis was conducted applying constant comparison techniques. People with experience of persisting symptoms contributed to study design and data analysis.

RESULTS: This article reports analysis of 24 interviews. The main themes include: the ' hard and heavy work ' of enduring and managing symptoms and accessing care; living with uncertainty, helplessness and fear, particularly over whether recovery is possible; the importance of finding the 'right' GP (understanding, empathy, and support needed); and recovery and rehabilitation: what would help?

CONCLUSION: This study will raise awareness among primary care professionals, and commissioners, of long-COVID and the range of symptoms people are experiencing. Patients require their GP to believe their symptoms and to demonstrate empathy and understanding. Ongoing support by primary care professionals during recovery and rehabilitation is crucial.}, } @article {pmid33034893, year = {2021}, author = {Halpin, S and O'Connor, R and Sivan, M}, title = {Long COVID and chronic COVID syndromes.}, journal = {Journal of medical virology}, volume = {93}, number = {3}, pages = {1242-1243}, pmid = {33034893}, issn = {1096-9071}, mesh = {COVID-19/*complications/epidemiology/*physiopathology/virology ; Cohort Studies ; Comorbidity ; Hospitalization/statistics & numerical data ; Humans ; SARS-CoV-2/*pathogenicity ; United Kingdom ; Post-Acute COVID-19 Syndrome ; }, } @article {pmid33029005, year = {2020}, author = {}, title = {Long COVID: let patients help define long-lasting COVID symptoms.}, journal = {Nature}, volume = {586}, number = {7828}, pages = {170}, doi = {10.1038/d41586-020-02796-2}, pmid = {33029005}, issn = {1476-4687}, mesh = {Betacoronavirus ; COVID-19 ; *Coronavirus Infections/complications ; Humans ; *Pandemics ; *Pneumonia, Viral/complications ; SARS-CoV-2 ; *Treatment Outcome ; }, } @article {pmid32998879, year = {2020}, author = {}, title = {Managing long covid: don't overlook olfactory dysfunction.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m3771}, doi = {10.1136/bmj.m3771}, pmid = {32998879}, issn = {1756-1833}, } @article {pmid32978178, year = {2020}, author = {Hopkins, C and Burges Watson, DL and Kelly, C and Leary, V and Smith, BC}, title = {Managing long covid: don't overlook olfactory dysfunction.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m3736}, doi = {10.1136/bmj.m3736}, pmid = {32978178}, issn = {1756-1833}, mesh = {Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; Humans ; *Olfaction Disorders ; *Pandemics ; *Pneumonia, Viral ; Primary Health Care ; SARS-CoV-2 ; }, } @article {pmid32967479, year = {2020}, author = {Zoltie, T and Owen, K and Devigus, A and Kelly, S}, title = {COVID-19 decontamination procedures for photographic equipment in a secondary care setting.}, journal = {Journal of visual communication in medicine}, volume = {43}, number = {4}, pages = {184-189}, doi = {10.1080/17453054.2020.1796478}, pmid = {32967479}, issn = {1745-3062}, mesh = {Betacoronavirus/*isolation & purification ; *Built Environment ; COVID-19 ; Coronavirus Infections/*prevention & control ; Decontamination/*methods ; Humans ; Pandemics/*prevention & control ; Photography/*instrumentation ; Pneumonia, Viral/*prevention & control ; SARS-CoV-2 ; }, abstract = {This article provides an overview of how long COVID-19 (SARS-CoV-2) survives on the built environment, and reviews currently available resources to provide recommendations on effective decontamination of photographic equipment based within a secondary care setting.}, } @article {pmid32933925, year = {2020}, author = {Wise, J}, title = {Long covid: doctors call for research and surveillance to capture disease.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m3586}, doi = {10.1136/bmj.m3586}, pmid = {32933925}, issn = {1756-1833}, } @article {pmid32895219, year = {2020}, author = {Nabavi, N}, title = {Long covid: How to define it and how to manage it.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m3489}, doi = {10.1136/bmj.m3489}, pmid = {32895219}, issn = {1756-1833}, } @article {pmid32816711, year = {2020}, author = {Burgers, J}, title = {"Long covid": the Dutch response.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m3202}, doi = {10.1136/bmj.m3202}, pmid = {32816711}, issn = {1756-1833}, mesh = {Betacoronavirus ; COVID-19 ; Coronavirus Infections/*complications/epidemiology/*therapy ; Humans ; Internet ; Netherlands/epidemiology ; Pandemics ; Pneumonia, Viral/*complications/epidemiology/*therapy ; SARS-CoV-2 ; }, } @article {pmid32769591, year = {2020}, author = {Schultz, RA and Lachiewicz, PF}, title = {What's Important: Is "Spring Training" Necessary for Surgeons After a Long COVID-19 Off-Season?.}, journal = {The Journal of bone and joint surgery. American volume}, volume = {102}, number = {15}, pages = {1291-1292}, doi = {10.2106/JBJS.20.00485}, pmid = {32769591}, issn = {1535-1386}, mesh = {*Betacoronavirus ; COVID-19 ; *Clinical Competence ; *Coronavirus Infections ; Humans ; *Orthopedics ; *Pandemics ; *Pneumonia, Viral ; SARS-CoV-2 ; Time Factors ; Workload ; }, } @article {pmid32665317, year = {2020}, author = {Mahase, E}, title = {Covid-19: What do we know about "long covid"?.}, journal = {BMJ (Clinical research ed.)}, volume = {370}, number = {}, pages = {m2815}, doi = {10.1136/bmj.m2815}, pmid = {32665317}, issn = {1756-1833}, } @article {pmid32517822, year = {2020}, author = {Thai, PQ and Toan, DTT and Son, DT and Van, HTH and Minh, LN and Hung, LX and Toan, NV and Hoat, LN and Luong, DH and Khue, LN and Khoa, NT and Huong, LT}, title = {Factors associated with the duration of hospitalisation among COVID-19 patients in Vietnam: A survival analysis.}, journal = {Epidemiology and infection}, volume = {148}, number = {}, pages = {e114}, pmid = {32517822}, issn = {1469-4409}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Betacoronavirus ; COVID-19 ; COVID-19 Testing ; COVID-19 Vaccines ; Child ; Child, Preschool ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnosis/*epidemiology ; Female ; Geography ; Hospitalization ; Humans ; Length of Stay/*statistics & numerical data ; Male ; Middle Aged ; Multivariate Analysis ; Pandemics ; Pneumonia, Viral/*epidemiology ; Proportional Hazards Models ; Quarantine/*statistics & numerical data ; Real-Time Polymerase Chain Reaction ; Residence Characteristics ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Survival Analysis ; *Travel-Related Illness ; Vietnam/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: The median duration of hospital stays due to COVID-19 has been reported in several studies on China as 10-13 days. Global studies have indicated that the length of hospitalisation depends on different factors, such as the time elapsed from exposure to symptom onset, and from symptom onset to hospital admission, as well as specificities of the country under study. The goal of this paper is to identify factors associated with the median duration of hospital stays of COVID-19 patients during the second COVID-19 wave that hit Vietnam from 5 March to 8 April 2020.

METHOD: We used retrospective data on 133 hospitalised patients with COVID-19 recorded over at least two weeks during the study period. The Cox proportional-hazards regression model was applied to determine the potential risk factors associated with length of hospital stay.

RESULTS: There were 65 (48.9%) females, 98 (73.7%) patients 48 years old or younger, 15 (11.3%) persons with comorbidities, 21 (16.0%) severely ill patients and 5 (3.8%) individuals with life-threatening conditions. Eighty-two (61.7%) patients were discharged after testing negative for the SARS-CoV-2 virus, 51 were still in the hospital at the end of the study period and none died. The median duration of stay in a hospital was 21 (IQR: 16-34) days. The multivariable Cox regression model showed that age, residence and sources of contamination were significantly associated with longer duration of hospitalisation.

CONCLUSION: A close look at how long COVID-19 patients stayed in the hospital could provide an overview of their treatment process in Vietnam, and support the country's National Steering Committee on COVID-19 Prevention and Control in the efficient allocation of resources over the next stages of the COVID-19 prevention period.}, } @article {pmid33775950, year = {2020}, author = {Callard, F}, title = {Epidemic Time: Thinking from the Sickbed.}, journal = {Bulletin of the history of medicine}, volume = {94}, number = {4}, pages = {727-743}, doi = {10.1353/bhm.2020.0093}, pmid = {33775950}, issn = {1086-3176}, mesh = {COVID-19/*psychology ; *Epidemics ; Fatigue Syndrome, Chronic/*psychology ; Historiography ; Humans ; Perception ; Posture ; Supine Position ; Writing ; }, abstract = {To experience an epidemic while lying on a sickbed opens up other ways of thinking through time, epidemics, and sequence from those developed by Charles Rosenberg in his 1989 essay, "What Is an Epidemic?". In this essay, a patient recovering from COVID-19 analyzes how histories of epidemics often follow the logic proposed by the discipline of epidemiology itself: a focus on acute cases and on a tracking of the "peak(s)" often means that longer temporalities of suffering are hidden. In contrast, this essay follows "Long Covid"-an illness collectively made and named by patients, which changed how the natural history of a new disease (COVID-19) was being mapped out by conventional scientific experts. Long Covid conceptualizes time differently from common categories and prefixes used in medicine and epidemiology, such as the "chronic" or the "post-." The collective labor of ill people thinking from the sickbed-both those with Long Covid and those working to bring to visibility other illnesses and the sequelae of other epidemics-has allowed other possible arrangements of sick bodies, symptoms, and diagnostic classifications to come into view. These arrangements hold potential for historians of medicine, as well as for clinical scientists.}, }